PMID- 26537989 TI - Case report: anti-glomerular basement membrane antibody disease with normal renal function. AB - BACKGROUND: Anti-glomerular basement membrane (GBM) antibody disease is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis caused by autoantibodies against the alpha3-chain of type IV collagen in the GBM. CASE PRESENTATION: An 8-year-old girl with hematuria and proteinuria due to anti GBM nephritis was diagnosed with hematuria and proteinuria during a school urine screening program. Her blood pressure and serum creatinine levels were normal. Her hematuria and proteinuria persisted for several months. Since a spot urine protein to creatinine ratio was around 7 g/g Cre, a percutaneous renal biopsy was performed. Immunofluorescent staining demonstrated a linear pattern for immunoglobulin G along the entire GBM. Chest computed tomography was normal. Anti GBM antibody assays were reported as slightly raised; thus, the diagnosis was anti-GBM disease with normal renal function. Treatment included plasma exchange, intravenous high-dose methylprednisolone, and cyclophosphamide as a mainstay medication. The treatment was rapidly effective with an immediate decrease in anti-GBM titers and proteinuria. CONCLUSIONS: Cases of anti-GBM disease with normal renal function in children are rare. Treatment in children has not been established; therefore, clinicians need to carefully select an effective treatment because the prognosis is poor. PMID- 26537988 TI - Network meta-analysis incorporating randomized controlled trials and non randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities. AB - Network meta-analysis is increasingly used to allow comparison of multiple treatment alternatives simultaneously, some of which may not have been compared directly in primary research studies. The majority of network meta-analyses published to date have incorporated data from randomized controlled trials (RCTs) only; however, inclusion of non-randomized studies may sometimes be considered. Non-randomized studies can complement RCTs or address some of their limitations, such as short follow-up time, small sample size, highly selected population, high cost, and ethical restrictions. In this paper, we discuss the challenges and opportunities of incorporating both RCTs and non-randomized comparative cohort studies into network meta-analysis for assessing the safety and effectiveness of medical treatments. Non-randomized studies with inadequate control of biases such as confounding may threaten the validity of the entire network meta-analysis. Therefore, identification and inclusion of non-randomized studies must balance their strengths with their limitations. Inclusion of both RCTs and non-randomized studies in network meta-analysis will likely increase in the future due to the growing need to assess multiple treatments simultaneously, the availability of higher quality non-randomized data and more valid methods, and the increased use of progressive licensing and product listing agreements requiring collection of data over the life cycle of medical products. Inappropriate inclusion of non randomized studies could perpetuate the biases that are unknown, unmeasured, or uncontrolled. However, thoughtful integration of randomized and non-randomized studies may offer opportunities to provide more timely, comprehensive, and generalizable evidence about the comparative safety and effectiveness of medical treatments. PMID- 26537990 TI - MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a. AB - Nonalcoholic fibrosing steatohepatitis is a uniform process throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested to modulate cellular processes in liver diseases. However, the functional role of miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this study, we systematically analyzed the hepatic miRNAs by microarray analysis in nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by methionine choline deficient (MCD) diet. We identified 19 up-regulated and 18 down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs, miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p. Hepatic miR-146a 5p was down-regulated in fibrosing steatohepatitis, but its target genes Wnt1 and Wnt5a and their consequent effectors alpha-SMA and Col-1 were significantly up regulated. In addition, miR-146a-5p was downregulated, whilst Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells (HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in HSCs inhibited HSC activation and proliferation, which concomitant with the decreased expressions of Wnt1, Wnt5a, alpha-SMA and Col-1. In conclusion, miR-146a-5p suppresses activation and proliferation of HSCs in the progress of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent effectors alpha SMA and Col-1. PMID- 26537991 TI - Capsular Outcomes Differ with Capsulorhexis Sizes after Pediatric Cataract Surgery: A Randomized Controlled Trial. AB - Capsular outcomes of anterior/posterior capsulorhexis opening (ACO/PCO) are essential for performing a secondary in-the-bag intraocular lens implantation. To compare the capsular outcomes with different primary capsulorhexis sizes, Thirty eight eligible patients (45 eyes) were randomly assigned to three groups by anterior capsulorhexis diameter (Group A: 3.0-3.9, Group B: 4.0-5.0, and Group C: 5.1-6.0 mm). The areas of ACO/PCO and posterior capsule opening opacity (PCOO) as primary outcomes, while, the incidence of visual axis opacity (VAO) as secondary outcome were measured at follow-up visits. Among the thirty eyes included in the final analysis, the mean area of the ACO decreased significantly, whereas the PCO enlarged with time. Group A had the highest anterior capsule constriction and percentage reduction, which increased with time. There were significant differences in the percentage reductions at 6 months and 1 year compared to 1 month in Group A and B. Group C had the highest posterior capsule enlargement. The percentage of PCOO to PCO area and the incidence of VAO was highest in Group A and lowest in Group C. Thus, Capsulorhexis diameter of 4.0-5.0 mm may yield better capsular outcomes, considering moderate contraction of ACO, moderate enlargement of PCO, and lower percentage of PCOO and VAO. PMID- 26537992 TI - Synthesis of Migrastatin Analogues as Inhibitors of Tumour Cell Migration: Exploring Structural Change in and on the Macrocyclic Ring. AB - Invited for the cover of this issue are Paul V. Murphy and co-workers at the National University of Ireland Galway (NUI Galway) and Warsaw University. The image depicts MGSTA-6 giving a stop signal to tumour cells that are on the move. Read the full text of the article at 10.1002/chem.201502861. PMID- 26537994 TI - Strain-driven band inversion and topological aspects in Antimonene. AB - Searching for the two-dimensional (2D) topological insulators (TIs) with large bulk band gaps is the key to achieve room-temperature quantum spin Hall effect (QSHE). Using first-principles calculations, we demonstrated that the recently proposed antimonene [Zhang et al., Angew. Chem. Int. Ed. 54, 3112-3115 (2015)] can be tuned to a 2D TI by reducing the buckling height of the lattice which can be realized under tensile strain. The strain-driven band inversion in the vicinity of the Fermi level is responsible for the quantum phase transition. The buckled configuration of antimonene enables it to endure large tensile strain up to 18% and the resulted bulk band gap can be as large as 270 meV. The tunable bulk band gap makes antimonene a promising candidate material for achieving quantum spin Hall effect (QSH) at high temperatures which meets the requirement of future electronic devices with low power consumption. PMID- 26537993 TI - Functional analysis of Paracoccidioides brasiliensis 14-3-3 adhesin expressed in Saccharomyces cerevisiae. AB - BACKGROUND: 14-3-3 proteins comprise a family of eukaryotic multifunctional proteins involved in several cellular processes. The Pb14-3-3 of Paracoccidioides brasiliensis seems to play an important role in the Paracoccidioides-host interaction. Paracoccidioides brasiliensis is an etiological agent of paracoccidioidomycosis, which is a systemic mycosis that is endemic in Latin America. In the initial steps of the infection, Paracoccidioides spp. synthetizes adhesins that allow it to adhere and invade host cells. Therefore, the aim of this work was to perform a functional analysis of Pb14-3-3 using Saccharomyces cerevisiae as a model. RESULTS: The functional analysis of Pb14-3-3 was performed in S. cerevisiae, and it was found that Pb14-3-3 partially complemented S. cerevisiae proteins Bmh1p and Bmh2p, which are recognized as two yeast 14-3-3 homologues. When we evaluated the adhesion profile of S. cerevisiae transformants, Pb14-3-3 acted as an adhesin in S. cerevisiae; however, Bmh1p did not show this function. The influence of Pb14-3-3 in S. cerevisiae ergosterol pathway was also evaluated and our results showed that Pb14-3-3 up-regulates genes involved in ergosterol biosynthesis. CONCLUSIONS: Our data showed that Pb14 3-3 was able to partially complement Bmh1p and Bmh2p proteins in S. cerevisiae; however, we suggest that Pb14-3-3 has a differential role as an adhesin. In addition, Pb-14-3-3 may be involved in Paracoccidioides spp. ergosterol biosynthesis which makes it an interest as a therapeutic target. PMID- 26537995 TI - Targeted therapies for treatment of non-small cell lung cancer--Recent advances and future perspectives. AB - Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer. PMID- 26537996 TI - Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review. AB - This systematic review provides a comprehensive, up-to-date summary of traumatic brain injury (TBI) epidemiology in Europe, describing incidence, mortality, age, and sex distribution, plus severity, mechanism of injury, and time trends. PubMed, CINAHL, EMBASE, and Web of Science were searched in January 2015 for observational, descriptive, English language studies reporting incidence, mortality, or case fatality of TBI in Europe. There were no limitations according to date, age, or TBI severity. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. Data were presented narratively. Sixty-six studies were included in the review. Country level data were provided in 22 studies, regional population or treatment center catchment area data were reported by 44 studies. Crude incidence rates varied widely. For all ages and TBI severities, crude incidence rates ranged from 47.3 per 100,000, to 694 per 100,000 population per year (country-level studies) and 83.3 per 100,000, to 849 per 100,000 population per year (regional-level studies). Crude mortality rates ranged from 9 to 28.10 per 100,000 population per year (country-level studies), and 3.3 to 24.4 per 100,000 population per year (regional-level studies.) The most common mechanisms of injury were traffic accidents and falls. Over time, the contribution of traffic accidents to total TBI events may be reducing. Case ascertainment and definitions of TBI are variable. Improved standardization would enable more accurate comparisons. PMID- 26537997 TI - Gambling and gambling policy in Norway--an exceptional case. AB - AIMS: The aim of this paper is to provide an overview of the development and current status of gambling and gambling policy in Norway. METHODS: An overview of the research literature and official documents and websites. RESULTS: Gambling on electronic gaming machines (EGMs) increased dramatically in the 1990s in response to technological development and liberalization of gambling policy. Restrictions on availability of EGM gambling occurred from 2006 to 2009 and included a ban on note acceptors, a temporary ban on EGMs and re-introduction of fewer and less aggressive machines under a state monopoly. The restrictions led to significant decreases in total gambling turnover, and several studies suggest that they led to fewer gambling and gambling problems. Various factors may explain why the restrictions were politically feasible. These include media coverage of gambling concerns and economic compensation for revenue losses under the monopoly. CONCLUSIONS: In an international context of deregulation of gambling markets, the Norwegian policy restrictions on gambling availability have represented an exceptional case and provide a rare opportunity to explore the outcomes of such regulations. Overall, studies suggest that the policy restrictions have led to reductions in gambling expenditures and problem gambling. PMID- 26537998 TI - Associations of workplace bullying and harassment with stress reactions: a two year follow-up study. AB - The purpose of this prospective study was to investigate the effect of the patterning of workplace bullying and harassment over two time points (chronic, remission, onset, and never) on psychological and physical stress reactions. The subjects were 543 workers at welfare facilities for the elderly in Japan who completed a self-administered questionnaire at Time 1 (from August to September, 2009) and at Time 2 (from September to October, 2011). Workplace bullying and harassment were assessed using the Negative Acts Questionnaire (NAQ). Stress reactions were assessed using the Brief Job Stress Questionnaire. In the multiple logistic regression analyses, onset of person-related bullying was significantly (p<0.05) positively associated with both psychological and physical stress reactions at Time 2. Chronic form of person-related bullying was significantly (p<0.05) positively associated with psychological stress reaction at Time 2. Onset of sexual harassment was significantly (p<0.05) positively, and remission of sexual harassment was significantly (p<0.05) negatively associated with physical stress reaction at Time 2. Onset and chronic form of person-related bullying and onset of sexual harassment can cause stress reactions. Remission of sexual harassment can terminate physical stress reaction. PMID- 26537999 TI - Job demands and resting and napping opportunities for nurses during night shifts: impact on sleepiness and self-evaluated quality of healthcare. AB - The aim of this field study is to describe night shift resting and napping strategies and to examine their beneficial effects on sleepiness and quality of work. The study was carried out with 16 nurses working in an intensive care unit. Data collected during 20 night shifts were related to job demands (systematic observations), to the duration and timing of rests and naps taken by nurses (systematic observations, sleep diaries), to sleepiness (Karolinska Sleepiness Scale), and to quality of work scores (visual analog scale). The results showed that the number of rests and naps depended on the job demands. Resting and napping lowered the levels of sleepiness at the end of the shift. There was no direct relationship between sleepiness and the quality of work score. Discussions about the choice of indicators for the quality of work are necessary. Suggestions for implementing regulations for prescribed napping during night shifts are presented. PMID- 26538000 TI - Amines as occupational hazards for visual disturbance. AB - Various amines, such as triethylamine and N,N-dimethylethylamine, have been reported to cause glaucopsia in workers employed in epoxy, foundry, and polyurethane foam industries. This symptom has been related to corneal edema and vesicular collection of fluid within the corneal subepithelial cells. Exposure to amine vapors for 30 min to several hours leads to blurring of vision, a blue-grey appearance of objects, and halos around lights, that are probably reversible. Concentration-effect relationships have been established. The visual disturbance is considered a nuisance, as it could cause onsite accidents, impair work efficiency, and create difficulties in driving back home. Occupational exposure limits have been established for some amines, but there is shortage of criteria. Volatility factors, such as vapor pressure, should be considered in industrial settings to prevent human ocular risks, while trying to reduce levels of hazardous amines in the atmosphere. PMID- 26538001 TI - The education and practice program for medical students with quantitative and qualitative fit test for respiratory protective equipment. AB - Tuberculosis infection is prevalent in Korea and health care workers are vulnerable to tuberculosis infection in the hospital. The aims of this study were to develop and validate an education program that teaches senior medical students how to wear and choose the proper size and type of respiratory protective equipment (RPE), which may help reduce the risk of contracting Mycobacterium tuberculosis (MTB) from patients. Overall, 50 senior medical students participated in this education program. Methods of choosing the proper type of RPE, performing a fit check of the RPE, and choosing a suitable mask size were taught by certified instructors using the real-time quantitative fit test (QNFT). The validity of education program was evaluated with qualitative fit test (QLFT) before and after the education as pass or fail. The education program was effective, as shown by the significantly pass rate (increased 30 to 74%) in the QLFT after the education program (p<0.05). Among study participants, changing mask size from medium to small significantly increased the pass rate (p<0.001). Incorporation of this program into the medical school curriculum may help reduce risk of MTB infection in medical students working in the hospital. PMID- 26538002 TI - Work-home interface stress: an important predictor of emotional exhaustion 15 years into a medical career. AB - The importance of work-home interface stress can vary throughout a medical career and between genders. We studied changes in work-home interface stress over 5 yr, and their prediction of emotional exhaustion (main dimension of burn-out), controlled for other variables. A nationwide doctor cohort (NORDOC; n=293) completed questionnaires at 10 and 15 yr after graduation. Changes over the period were examined and predictors of emotional exhaustion analyzed using linear regression. Levels of work-home interface stress declined, whereas emotional exhaustion stayed on the same level. Lack of reduction in work-home interface stress was an independent predictor of emotional exhaustion in year 15 (beta= 0.21, p=0.001). Additional independent predictors were reduction in support from colleagues (beta=0.11, p=0.04) and emotional exhaustion at baseline (beta=0.62, p<0.001). Collegial support was a more important predictor for men than for women. In separate analyses, significant adjusted predictors were lack of reduction in work-home interface stress among women, and reduction of collegial support and lack of reduction in working hours among men. Thus, change in work home interface stress is a key independent predictor of emotional exhaustion among doctors 15 yr after graduation. Some gender differences in predictors of emotional exhaustion were found. PMID- 26538003 TI - Different gene expressions between cattle and yak provide insights into high altitude adaptation. AB - DNA sequence variation has been widely reported as the genetic basis for adaptation, in both humans and other animals, to the hypoxic environment experienced at high altitudes. However, little is known about the patterns of gene expression underlying such hypoxic adaptations. In this study, we examined the differences in the transcriptomes of four organs (heart, kidney, liver and lung) between yak and cattle, a pair of closely related species distributed at high and low altitudes respectively. Of the four organs examined, heart shows the greatest differentiation between the two species in terms of gene expression profiles. Detailed analyses demonstrated that some genes associated with the oxygen supply system and the defense systems that respond to threats of hypoxia are differentially expressed. In addition, genes with significantly differentiated patterns of expression in all organs exhibited an unexpected uniformity of regulation along with an elevated frequency of nonsynonymous substitutions. This co-evolution of protein sequences and gene expression patterns is likely to be correlated with the optimization of the yak metabolic system to resist hypoxia. PMID- 26538004 TI - Guidelines for the investigation and management of nodular lymphocyte predominant Hodgkin lymphoma. PMID- 26538006 TI - Remote control of self-assembled microswimmers. AB - Physics governing the locomotion of microorganisms and other microsystems is dominated by viscous damping. An effective swimming strategy involves the non reciprocal and periodic deformations of the considered body. Here, we show that a magnetocapillary-driven self-assembly, composed of three soft ferromagnetic beads, is able to swim along a liquid-air interface when powered by an external magnetic field. More importantly, we demonstrate that trajectories can be fully controlled, opening ways to explore low Reynolds number swimming. This magnetocapillary system spontaneously forms by self-assembly, allowing miniaturization and other possible applications such as cargo transport or solvent flows. PMID- 26538007 TI - The 10m incremental shuttle walk test is a highly reliable field exercise test for patients referred to cardiac rehabilitation: a retest reliability study. AB - OBJECTIVES: To determine the retest reliability of the 10m incremental shuttle walk test (ISWT) in a mixed cardiac rehabilitation population. DESIGN: Participants completed two 10m ISWTs in a single session in a repeated measures study. Ten participants completed a third 10m ISWT as part of a pilot study. SETTING: Hospital physiotherapy department. PARTICIPANTS: 62 adults aged a mean of 68 years (SD 10) referred to a cardiac rehabilitation program. MAIN OUTCOME MEASURES: Retest reliability of the 10m ISWT expressed as relative reliability and measurement error. Relative reliability was expressed in a ratio in the form of an intraclass correlation coefficient (ICC) and measurement error in the form of the standard error of measurement (SEM) and 95% confidence intervals for the group and individual. RESULTS: There was a high level of relative reliability over the two walks with an ICC of .99. The SEMagreement was 17m, and a change of at least 23m for the group and 54m for the individual would be required to be 95% confident of exceeding measurement error. CONCLUSIONS: The 10m ISWT demonstrated good retest reliability and is sufficiently reliable to be applied in practice in this population without the use of a practice test. PMID- 26538008 TI - Stable ultrathin partially oxidized copper film electrode for highly efficient flexible solar cells. AB - Advances in flexible optoelectronic devices have led to an increasing need for developing highly efficient, low-cost, flexible transparent conducting electrodes. Copper-based electrodes have been unattainable due to the relatively low optical transmission and poor oxidation resistance of copper. Here, we report the synthesis of a completely continuous, smooth copper ultra-thin film via limited copper oxidation with a trace amount of oxygen. The weakly oxidized copper thin film sandwiched between zinc oxide films exhibits good optoelectrical performance (an average transmittance of 83% over the visible spectral range of 400-800 nm and a sheet resistance of 9 Omega sq(-1)) and strong oxidation resistance. These values surpass those previously reported for copper-based electrodes; further, the record power conversion efficiency of 7.5% makes it clear that the use of an oxidized copper-based transparent electrode on a polymer substrate can provide an effective solution for the fabrication of flexible organic solar cells. PMID- 26538009 TI - Factors associated with outcome and gradual improvement in survival over time in 1065 equine neonates admitted to an intensive care unit. AB - REASONS FOR PERFORMING STUDY: There is a paucity of information regarding the association between common disorders and outcome over time in a large population of ill equine neonates. OBJECTIVES: To describe the relative frequency of neonatal disorders in a large population of foals admitted to a neonatal intensive care unit, to determine the disorders and factors associated with nonsurvival and determine if the outcome of ill neonatal foals has improved over time. STUDY DESIGN: Retrospective study. METHODS: Cases were selected from equine neonatal (<=14 days of age) admissions between 1982 and 2008. Multivariable logistic regression was used to identify the disorders, clinical parameters and laboratory variables associated with nonsurvival or natural death and assess survival over time after accounting for potential confounding variables. RESULTS: A total of 1065 foals were included in the study. Overall, 775 of 1065 (72.8%) foals survived to be discharged from the hospital and 290 (27.2%) foals were nonsurvivors. Age at admission, sepsis score, proportion of foals with positive blood cultures and proportion of survivors were significantly different (P<0.001) between primary disease categories. Variables retained in the multivariable model for nonsurvival included positive blood culture, neutrophils <2.28 * 109 /l, temperature <=37.6 degrees C, bicarbonate, PCO2 , presence of infectious orthopaedic disorders and sepsis score. The adjusted odds of survival for foals admitted in the 2000s were approximately 3.4 (95% CI = 1.9-6.0, P<0.001) times higher than that of foals admitted in the 1980s. CONCLUSIONS: Primary disorders, sepsis, temperature, acid base status and neutropenia are the main factors that affect outcome in this population of equine neonates. The survival of foals admitted to a neonatal intensive care unit has increased dramatically over a 26 year period. PMID- 26538010 TI - Categorization in infancy: labeling induces a persisting focus on commonalities. AB - Recent studies with infants and adults demonstrate a facilitative role of labels in object categorization. A common interpretation is that labels highlight commonalities between objects. However, direct evidence for such a mechanism is lacking. Using a novel object category with spatially separate features that are either of low or high variability across the stimulus set, we tracked 12-month olds' attention to object features during learning and at test. Learning occurred in both conditions, but what was learned depended on whether or not labels were heard. A detailed analysis of eye movements revealed that infants in the two conditions employed different object processing strategies. In the silent condition, looking patterns were governed exclusively by the variability of object parts. In the label condition, infants' categorization performance was linked to their relative attention to commonalities. Moreover, the commonality focus persisted after learning even in the absence of labels. These findings constitute the first experimental evidence that labels induce a persistent focus on commonalities. PMID- 26538011 TI - Personality prototype as a risk factor for eating disorders. AB - OBJECTIVE: To establish whether the risk of suffering from an eating disorder (ED) is associated with the high-functioning, undercontrolled, or overcontrolled personality prototype groups. METHOD: The Revised NEO Personality Inventory (NEO PI-R) and the Eating Disorder Inventory 2 (EDI-2) were administered to 69 patients diagnosed as suffering from EDs (cases) and 89 people free of any ED symptoms (control group). A cluster analysis was carried out to divide the participants into three groups based on their scores in the Big Five personality dimensions. A logistic regression model was then created. RESULTS: Participants in the undercontrolled group had a risk of suffering from an ED 6.517 times higher than those in the high-functioning group (p = 0.019; odds ratio [OR] = 6.517), while those in the overcontrolled subgroup had a risk of ED 15.972 times higher than those in the high-functioning group. CONCLUSIONS: Two personality subtypes were identified in which the risk of EDs was six times higher (the undercontrolled group) and almost 16 times higher (the overcontrolled group). Prevention and treatment programs for ED could benefit from focusing on the abovementioned personality profiles. PMID- 26538013 TI - Secular trends of the impact of overweight and obesity on hypertension in Japan, 1980-2010. PMID- 26538012 TI - Regulation of urinary bladder function by protein kinase C in physiology and pathophysiology. AB - BACKGROUND: Protein kinase C (PKC) is expressed in many tissues and organs including the urinary bladder, however, its role in bladder physiology and pathophysiology is still evolving. The aim of this review was to evaluate available evidence on the involvement of PKC in regulation of detrusor contractility, muscle tone of the bladder wall, spontaneous contractile activity and bladder function under physiological and pathophysiological conditions. METHODS: This is a non-systematic review of the published literature which summarizes the available animal and human data on the role of PKC signaling in the urinary bladder under different physiological and pathophysiological conditions. A wide PubMed search was performed including the combination of the following keywords: "urinary bladder", "PKC", "detrusor contractility", "bladder smooth muscle", "detrusor relaxation", "peak force", "detrusor underactivity", "partial bladder outlet obstruction", "voltage-gated channels", "bladder nerves", "PKC inhibitors", "PKC activators". Retrieved articles were individually screened for the relevance to the topic of this review with 91 citations being selected and included in the data analysis. DISCUSSION: Urinary bladder function includes the ability to store urine at low intravesical pressure followed by a subsequent release of bladder contents due to a rapid phasic contraction that is maintained long enough to ensure complete emptying. This review summarizes the current concepts regarding the potential contribution of PKC to contractility, physiological voiding, and related signaling mechanisms involved in the control of both the storage and emptying phases of the micturition cycle, and in dysfunctional voiding. Previous studies linked PKC activation exclusively with an increase in generation of the peak force of smooth muscle contraction, and maximum force generation in the lower urinary tract. More recent data suggests that PKC presents a broader range of effects on urinary bladder function including regulation of storage, emptying, excitability of the detrusor, and bladder innervation. In this review, we evaluated the mechanisms of peripheral and local regulation of PKC signaling in the urinary bladder, and their impact on different phases of the micturition cycle under physiological and pathophysiological conditions. PMID- 26538016 TI - The role of life histories and trophic interactions in population recovery. AB - Factors affecting population recovery from depletion are at the focus of wildlife management. Particularly, it has been debated how life-history characteristics might affect population recovery ability and productivity. Many exploited fish stocks have shown temporal changes towards earlier maturation and reduced adult body size, potentially owing to evolutionary responses to fishing. Whereas such life-history changes have been widely documented, their potential role on stock's ability to recover from exploitation often remains ignored by traditional fisheries management. We used a marine ecosystem model parameterized for Southeastern Australian ecosystem to explore how changes towards "faster" life histories might affect population per capita growth rate r. We show that for most species changes towards earlier maturation during fishing have a negative effect (3-40% decrease) on r during the recovery phase. Faster juvenile growth and earlier maturation were beneficial early in life, but smaller adult body sizes reduced the lifetime reproductive output and increased adult natural mortality. However, both at intra- and inter-specific level natural mortality and trophic position of the species were as important in determining r as species longevity and age of maturation, suggesting that r cannot be predicted from life-history traits alone. Our study highlights that factors affecting population recovery ability and productivity should be explored in a multi-species context, where both age-specific fecundity and survival schedules are addressed simultaneously. It also suggests that contemporary life-history changes in harvested species are unlikely to increase their resilience and recovery ability. PMID- 26538017 TI - In search for symmetries in the metabolism of cancer. AB - Even though aerobic glycolysis, or the Warburg effect, is arguably the most common trait of metabolic reprogramming in cancer, it is unobserved in certain tumor types. Systems biology advocates a global view on metabolism to dissect which traits are consistently reprogrammed in cancer, and hence likely to constitute an obligate step for the evolution of cancer cells. We refer to such traits as symmetric. Here, we review early systems biology studies that attempted to reveal symmetric traits in the metabolic reprogramming of cancer, discuss the symmetry of reprogramming of nucleotide metabolism, and outline the current limitations that, if unlocked, could elucidate whether symmetries in cancer metabolism may be claimed. PMID- 26538018 TI - Sensitization to reactive diluents and hardeners in epoxy resin systems. IVDK data 2002-2011. Part I: reaction frequencies. AB - BACKGROUND: Epoxy resin systems (ERSs), consisting of resins, reactive diluents, and hardeners, are indispensable in many branches of industry. In order to develop less sensitizing ERS formulations, knowledge of the sensitizing properties of single components is mandatory. OBJECTIVES: To analyse the frequency of sensitization in the patients concerned, as one integral part of a research project on the sensitizing potency of epoxy resin compounds (FP-0324). METHODS: A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2011, and a comparison of reaction frequencies with (surrogate) exposure data, were performed. RESULTS: Almost half of the patients sensitized to epoxy resin were additionally sensitized to reactive diluents or hardeners. Among the reactive diluents, 1,6-hexanediol diglycidyl ether was the most frequent allergen, followed by 1,4-butanediol diglycidyl ether, phenyl glycidyl ether, and p-tert-butylphenyl glycidyl ether. Among the hardeners, m-xylylene diamine (MXDA) and isophorone diamine (IPDA) were the most frequent allergens. According to the calculated exposure-related frequency of sensitization, MXDA seems to be a far more important sensitizer than IPDA. Up to 60% of the patients sensitized to hardeners and 15-20% of those sensitized to reactive diluents do not react to epoxy resin. CONCLUSIONS: In cases of suspected contact allergy to an ERS, a complete epoxy resin series must be patch tested from the start. PMID- 26538019 TI - Elaboration of a nomogram to predict non sentinel node status in breast cancer patients with positive sentinel node, intra-operatively assessed with one step nucleic acid amplification method. AB - BACKGROUNDS: Tumor-positive sentinel node(SLN) biopsy results in a risk of nonsentinel node metastases in case of micro and macro metastases ranging from 20 to 50 %, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. Thus, the development of a mathematical model for predicting patient-specific risk of non sentinel node(NSLN) metastases is strongly warranted. METHODS: The following parameters were recorded: CLINICAL: hospital, age, medical record number Bio-pathological: tumor (T) size, grading (G), multifocality, histological type, LVI, ER-PR status, HER-2, ki67, molecular classification (luminal A, luminal B, HER2 like, triple negative) Sentinel and nonsentinel lymph node related: number of removed SLNs, number of positive and negative SLNs, copy number of positive sentinel nodes, ratio: number of positive SLNs to number of removed SLNs, number of removed and number of positive nodes after ALND. A total of 2460 patients have been included in the database. All the patients have been provided by the authors of this paper. RESULTS: Multivariate logistic regression analysis demonstrated that only the number of a CK19 mRNA copies (p < 0.0001), T size (p < 0.0001) and LVI (p < 0.0001) were associated with NSN metastases. The discrimination of the model, quantified with the area under the receiver operating characteristics curve, was 0.71 (95 %, C.I. 0.69 0.73), thus confirming a good level of reliability. CONCLUSIONS: The nomogram may be employed by the surgeon as a decision making tool on whether to perform an intraoperative axillary lymph node dissection on breast cancer patients with SLN positive. The large population employed and the standardized method of measuring the value of CK19 mRNA copies are appropiate prerequisites for a reliable nomogram. PMID- 26538020 TI - Erratum. PMID- 26538021 TI - Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice. AB - Lysyl oxidases are required for collagen and elastin cross-linking and extracellular matrix maturation including in bone. The lysyl oxidase family consists of lysyl oxidase (LOX) and 4 isoforms (LOXL1-4). Here we investigate whether deletion of LOXL1, which has been linked primarily to elastin maturation, leads to skeletal abnormalities. Left femurs (n = 8), L5 vertebrae (n = 8), and tibiae (n = 8) were analyzed by micro-computed tomography in 13-week-old wild type (WT) and LOXL1-/- male and female mice. Right femurs (n = 8) were subjected to immunohistochemistry for LOXL1, and histochemical/histology analyses of osteoclasts and growth plates. Sera from all mice were analyzed for bone turnover markers. Results indicate strong expression of LOXL1 in wild-type growth plates in femurs. Significant deterioration of trabecular bone structure in long bones and vertebrae from female was observed but not from male, mutant mice compared with WT. Decreases in BV/TV, Conn.D, trabecular thickness, and number in the femoral distal metaphysis were observed in female, but not in male, mutant mice. Trabecular spacing was increased significantly in femurs of female mutant mice. Findings were similar in trabeculae of L5 vertebrae from female mutant mice. The number of TRAP positive osteoclasts at the trabecular bone surface was increased in female mutant mice compared with WT females, consistent with increased serum RANKL and decreased OPG levels. Analysis of bone turnover markers confirmed increased bone resorption as indicated by significantly elevated CTX-1 in the serum of female LOXL1-/- mice compared to their wild-type counterparts, as well as decreased bone formation as measured by decreased serum levels of PINP. Picrosirius red staining revealed a loss of heterogeneity in collagen organization in female LOXL1-/- mice only, with little to no yellow and orange birefringence. Organization was also impaired in chondrocyte columns in both female and male LOXL1-/- mice, but to a greater extent in females. Data indicate that LOXL1-/- mutant mice develop appendicular and axial skeletal phenotypes characterized by decreased bone volume fraction and compromised trabecular microstructure, predominantly in females. PMID- 26538022 TI - A complex of Rab13 with MICAL-L2 and alpha-actinin-4 is essential for insulin dependent GLUT4 exocytosis. AB - Insulin promotes glucose uptake into skeletal muscle through recruitment of glucose transporter 4 (GLUT4) to the plasma membrane. Rab GTPases are molecular switches mobilizing intracellular vesicles, and Rab13 is necessary for insulin regulated GLUT4-vesicle exocytic translocation in muscle cells. We show that Rab13 engages the scaffold protein MICAL-L2 in this process. RNA interference mediated knockdown of MICAL-L2 or truncated MICAL-L2 (MICAL-L2-CT) impaired insulin-stimulated GLUT4 translocation. Insulin increased Rab13 binding to MICAL L2, assessed by pull down and colocalization under confocal fluorescence and structured illumination microscopies. Association was also visualized at the cell periphery using TIRF microscopy. Insulin further increased binding of MICAL-L2 to alpha-actinin-4 (ACTN4), a protein involved in GLUT4 translocation. Rab13, MICAL L2, and ACTN4 formed an insulin-dependent complex assessed by pull down and confocal fluorescence imaging. Of note, GLUT4 associated with the complex in response to insulin, requiring the ACTN4-binding domain in MICAL-L2. This was demonstrated by pull down with distinct fragments of MICAL-L2 and confocal and structured illumination microscopies. Finally, expression of MICAL-L2-CT abrogated the insulin-dependent colocalization of Rab13 with ACTN4 or Rab13 with GLUT4. Our findings suggest that MICAL-L2 is an effector of insulin-activated Rab13, which links to GLUT4 through ACTN4, localizing GLUT4 vesicles at the muscle cell periphery to enable their fusion with the membrane. PMID- 26538023 TI - Mena-GRASP65 interaction couples actin polymerization to Golgi ribbon linking. AB - In mammalian cells, the Golgi reassembly stacking protein 65 (GRASP65) has been implicated in both Golgi stacking and ribbon linking by forming trans-oligomers through the N-terminal GRASP domain. Because the GRASP domain is globular and relatively small, but the gaps between stacks are large and heterogeneous, it remains puzzling how GRASP65 physically links Golgi stacks into a ribbon. To explore the possibility that other proteins may help GRASP65 in ribbon linking, we used biochemical methods and identified the actin elongation factor Mena as a novel GRASP65-binding protein. Mena is recruited onto the Golgi membranes through interaction with GRASP65. Depleting Mena or disrupting actin polymerization resulted in Golgi fragmentation. In cells, Mena and actin were required for Golgi ribbon formation after nocodazole washout; in vitro, Mena and microfilaments enhanced GRASP65 oligomerization and Golgi membrane fusion. Thus Mena interacts with GRASP65 to promote local actin polymerization, which facilitates Golgi ribbon linking. PMID- 26538024 TI - ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin. AB - ChromoShake is a three-dimensional simulator designed to find the thermodynamically favored states for given chromosome geometries. The simulator has been applied to a geometric model based on experimentally determined positions and fluctuations of DNA and the distribution of cohesin and condensin in the budding yeast centromere. Simulations of chromatin in differing initial configurations reveal novel principles for understanding the structure and function of a eukaryotic centromere. The entropic position of DNA loops mirrors their experimental position, consistent with their radial displacement from the spindle axis. The barrel-like distribution of cohesin complexes surrounding the central spindle in metaphase is a consequence of the size of the DNA loops within the pericentromere to which cohesin is bound. Linkage between DNA loops of different centromeres is requisite to recapitulate experimentally determined correlations in DNA motion. The consequences of radial loops and cohesin and condensin binding are to stiffen the DNA along the spindle axis, imparting an active function to the centromere in mitosis. PMID- 26538025 TI - Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry. AB - The establishment of left-right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites-cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer's vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite-associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease. PMID- 26538026 TI - Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates. AB - Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC-CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies. PMID- 26538027 TI - Dissecting in vivo steady-state dynamics of karyopherin-dependent nuclear transport. AB - Karyopherin-dependent molecular transport through the nuclear pore complex is maintained by constant recycling pathways of karyopherins coupled with the Ran dependent cargo catch-and-release mechanism. Although many studies have revealed the bidirectional dynamics of karyopherins, the entire kinetics of the steady state dynamics of karyopherin and cargo is still not fully understood. In this study, we used fluorescence recovery after photobleaching and fluorescence loss in photobleaching on live cells to provide convincing in vivo proof that karyopherin-mediated nucleocytoplasmic transport of cargoes is bidirectional. Continuous photobleaching of the cytoplasm of live cells expressing NLS cargoes led to progressive decrease of nuclear fluorescence signals. In addition, experimentally obtained kinetic parameters of karyopherin complexes were used to establish a kinetic model to explain the entire cargo import and export transport cycles facilitated by importin beta. The results strongly indicate that constant shuttling of karyopherins, either free or bound to cargo, ensures proper balancing of nucleocytoplasmic distribution of cargoes and establishes effective regulation of cargo dynamics by RanGTP. PMID- 26538028 TI - Auxilin facilitates membrane traffic in the early secretory pathway. AB - Coat protein complexes contain an inner shell that sorts cargo and an outer shell that helps deform the membrane to give the vesicle its shape. There are three major types of coated vesicles in the cell: COPII, COPI, and clathrin. The COPII coat complex facilitates vesicle budding from the endoplasmic reticulum (ER), while the COPI coat complex performs an analogous function in the Golgi. Clathrin coated vesicles mediate traffic from the cell surface and between the trans-Golgi and endosome. While the assembly and structure of these coat complexes has been extensively studied, the disassembly of COPII and COPI coats from membranes is less well understood. We describe a proteomic and genetic approach that connects the J-domain chaperone auxilin, which uncoats clathrin-coated vesicles, to COPII and COPI coat complexes. Consistent with a functional role for auxilin in the early secretory pathway, auxilin binds to COPII and COPI coat subunits. Furthermore, ER-Golgi and intra-Golgi traffic is delayed at 15 degrees C in swa2Delta mutant cells, which lack auxilin. In the case of COPII vesicles, we link this delay to a defect in vesicle fusion. We propose that auxilin acts as a chaperone and/or uncoating factor for transport vesicles that act in the early secretory pathway. PMID- 26538029 TI - Mcl-1 involvement in mitochondrial dynamics is associated with apoptotic cell death. AB - The B-cell lymphoma-2 (Bcl-2) family proteins are critical regulators of apoptosis and consist of both proapoptotic and antiapoptotic factors. Within this family, the myeloid cell leukemia factor 1 (Mcl-1) protein exists in two forms as the result of alternative splicing. The long variant (Mcl-1L) acts as an antiapoptotic factor, whereas the short isoform (Mcl-1S) displays proapoptotic activity. In this study, using splice-switching antisense oligonucleotides (ASOs), we increased the synthesis of Mcl-1S, which induced a concurrent reduction of Mcl-1L, resulting in increased sensitivity of cancer cells to apoptotic stimuli. The Mcl-1 ASOs also induced mitochondrial hyperpolarization and a consequent increase in mitochondrial calcium (Ca(2+)) accumulation. The high Mcl-1S/L ratio correlated with significant hyperfusion of the entire mitochondrial network, which occurred in a dynamin-related protein (Drp1) dependent manner. Our data indicate that the balance between the long and short variants of the Mcl-1 gene represents a key aspect of the regulation of mitochondrial physiology. We propose that the Mcl-1L/S balance is a novel regulatory factor controlling the mitochondrial fusion and fission machinery. PMID- 26538031 TI - Pyrene-Anderson-Modified CNTs as Anode Materials for Lithium-Ion Batteries. AB - An organo-functionalized polyoxometalate (POM)-pyrene hybrid (Py-Anderson) has been used for noncovalent functionalization of carbon nanotubes (CNTs) to give a Py-Anderson-CNT nanocomposite through pi-pi interactions. The as-synthesized nanocomposite was used as the anode material for lithium-ion batteries, and shows higher discharge capacities and better rate capacity and cycling stability than the individual components. When the current density was 0.5 mA cm(-2), the nanocomposite exhibited an initial discharge capacity of 1898.5 mA h g(-1) and a high discharge capacity of 665.3 mA h g(-1) for up to 100 cycles. AC impedance spectroscopy provides insight into the electrochemical properties and the charge transfer mechanism of the Py-Anderson-CNTs electrode. PMID- 26538030 TI - Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study. AB - BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. METHODS: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). RESULTS: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34 13:42), respectively. CONCLUSION: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing. PMID- 26538032 TI - Studying Edge Defects of Hexagonal Boron Nitride Using High-Resolution Electron Energy Loss Spectroscopy. AB - Studying the phonons of hexagonal boron nitride (h-BN) is important for understanding its thermal, electronic, and imaging applications. Herein, we applied high-resolution electron energy loss spectroscopy (HREELS) to monitor the presence of edge defects in h-BN films. We observed an edge phonon at 90.5 meV with the initial formation of island-like domains on Ru(0001), which subsequently weakens with respect to the bulk phonon as the islands congregate into a film. The presence of a weak edge phonon peak even at full surface coverage of the h-BN film indicates the sensitivity of HREELS in detecting line defects. A shoulder peak at ~160 meV assignable to sp(3) bonded modes was attributed to grain boundaries arising from misaligned domains. In addition, the strengths of substrate interaction and the rippling of the h-BN film can be judged from the shift in the phonon energy of the out-of-plane TO? mode. PMID- 26538033 TI - Ring-Polymer Molecular Dynamics for the Prediction of Low-Temperature Rates: An Investigation of the C((1)D) + H2 Reaction. AB - Quantum mechanical calculations are important tools for predicting the rates of elementary reactions, particularly for those involving hydrogen and at low temperatures where quantum effects become increasingly important. These approaches are computationally expensive, however, particularly when applied to complex polyatomic systems or processes characterized by deep potential wells. While several approximate techniques exist, many of these have issues with reliability. The ring-polymer molecular dynamics method was recently proposed as an accurate and efficient alternative. Here, we test this technique at low temperatures (300-50 K) by analyzing the behavior of the barrierless C((1)D) + H2 reaction over the two lowest singlet potential energy surfaces. To validate the theory, rate coefficients were measured using a supersonic flow reactor down to 50 K. The experimental and theoretical rates are in excellent agreement, supporting the future application of this method for determining the kinetics and dynamics of a wide range of low-temperature reactions. PMID- 26538034 TI - Fast Numerical Evaluation of Time-Derivative Nonadiabatic Couplings for Mixed Quantum-Classical Methods. AB - We have developed a numerical differentiation scheme that eliminates evaluation of overlap determinants in calculating the time-derivative nonadiabatic couplings (TDNACs). Evaluation of these determinants was the bottleneck in previous implementations of mixed quantum-classical methods using numerical differentiation of electronic wave functions in the Slater determinant representation. The central idea of our approach is, first, to reduce the analytic time derivatives of Slater determinants to time derivatives of molecular orbitals and then to apply a finite-difference formula. Benchmark calculations prove the efficiency of the proposed scheme showing impressive several-order-of magnitude speedups of the TDNAC calculation step for midsize molecules. PMID- 26538035 TI - Short-Range Catalyst-Surface Interactions Revealed by Heterodyne Two-Dimensional Sum Frequency Generation Spectroscopy. AB - Heterodyne 2D sum frequency generation spectroscopy is used to study a model CO2 reduction catalyst, Re(diCN-bpy) (CO)3Cl, as a monolayer on a gold surface. We show that short-range interactions with the surface can cause substantial line shape differences between vibrational bands from the same molecules. We explain this interaction as the result of couplings between CO vibrational modes of the catalyst molecules and the image dipoles on gold surface, which are sensitive to the relative distance between the molecule and the surface. Thus, by analysis of HD 2D SFG line-shape differences and polarization dependences of IR spectra, we can unambiguously determine the ensemble-averaged orientation of the molecules on the surface. The high sensitivity of HD 2D SFG spectra to short-range interactions can be applied to many other adsorbate-substrate interactions and therefore can serve as a unique tool to determine adsorbate orientations on surfaces. PMID- 26538036 TI - Plasmon-Mediated Electron Transport in Tip-Enhanced Raman Spectroscopic Junctions. AB - We combine experiment, theory, and first-principles-based calculations to study the light-induced plasmon-mediated electron transport characteristics of a molecular-scale junction. The experimental data show a nonlinear increase in electronic current perturbation when the focus of a chopped laser beam moves laterally toward the tip-sample junction. To understand this behavior and generalize it, we apply a combined theory of the electronic nonequilibrium formed upon decoherence of an optically triggered plasmon and first-principles transport calculations. Our model illustrates that the current via an adsorbed molecular monolayer increases nonlinearly as more energy is pumped into the junction due to the increasing availability of virtual molecular orbital channels for transport with higher injection energies. Our results thus illustrate light-triggered, plasmon-enhanced tunneling current in the presence of a molecular linker. PMID- 26538037 TI - Selective Electrochemical Generation of Hydrogen Peroxide from Water Oxidation. AB - Water is a life-giving source, fundamental to human existence, yet over a billion people lack access to clean drinking water. The present techniques for water treatment such as piped, treated water rely on time and resource intensive centralized solutions. In this work, we propose a decentralized device concept that can utilize sunlight to split water into hydrogen and hydrogen peroxide. The hydrogen peroxide can oxidize organics while the hydrogen bubbles out. In enabling this device, we require an electrocatalyst that can oxidize water while suppressing the thermodynamically favored oxygen evolution and form hydrogen peroxide. Using density functional theory calculations, we show that the free energy of adsorbed OH* can be used to determine selectivity trends between the 2e(-) water oxidation to H2O2 and the 4e(-) oxidation to O2. We show that materials which bind oxygen intermediates sufficiently weakly, such as SnO2, can activate hydrogen peroxide evolution. We present a rational design principle for the selectivity in electrochemical water oxidation and identify new material candidates that could perform H2O2 evolution selectively. PMID- 26538038 TI - CH+5: Symmetry and the Entangled Rovibrational Quantum States of a Fluxional Molecule. AB - Protonated methane, CH5+, is the prototypical example of a fluxional molecular system. The almost unconstrained angular motion of its five hydrogen atoms results in dynamical phenomena not found in rigid or semirigid molecules. Here it is shown that standard concepts to describe rotational quantum states of molecules can not be applied to CH5+ or any other fluxional system of the type ABn or Bn with n > 4 due to fundamental symmetry reasons. Instead, the ro vibrational states of CH5+ display a unique level scheme, which results from a complex entanglement of rotational and tunneling motions. A detailed analysis of the ro-vibrational quantum states of CH5+ based on full-dimensional quantum dynamics simulations is presented, and the effects of the Pauli principle are considered. The consequences for the interpretation of recent experimental results are highlighted PMID- 26538039 TI - Graphene-Based Photocatalysts for CO2 Reduction to Solar Fuel. AB - Recently, photocatalytic CO2 reduction for solar fuel production has attracted much attention because of its potential for simultaneously solving energy and global warming problems. Many studies have been conducted to prepare novel and efficient photocatalysts for CO2 reduction. Graphene, a two-dimensional material, has been increasingly used in photocatalytic CO2 reduction. In theory, graphene shows several remarkable properties, including excellent electronic conductivity, good optical transmittance, large specific surface area, and superior chemical stability. Attributing to these advantages, fabrication of graphene-based materials has been known as one of the most feasible strategies to improve the CO2 reduction performance of photocatalysts. This Perspective mainly focuses on the recent important advances in the fabrication and application of graphene based photocatalysts for CO2 reduction to solar fuels. The existing challenges and difficulties of graphene-based photocatalysts are also discussed for future application. PMID- 26538040 TI - High Carrier Mobility and Pronounced Light Absorption in Methyl-Terminated Germanene: Insights from First-Principles Computations. AB - On the basis of Herd-Scuseria-Emzerhof hybrid functional (HSE06) within the framework of density functional theory (DFT), we have computationally explored the intrinsic electronic and optical properties of 2D methyl-terminated germanene (GeCH3). GeCH3 monolayer possesses an opportune direct band gap of 1.76 eV, which can be effectively tuned by applying elastic strain and decreases with increasing the tensile strain, while it increases with small compressive strain. Also, anisotropic carrier mobility was disclosed in the armchair (x) and zigzag (y) directions of GeCH3 monolayer. Moreover, GeCH3 monolayer shows significant light absorption in the visible and ultraviolet range of solar spectrum and is attractive for light harvesting. The results can help us better understand the intrinsic properties of GeCH3 and provide reliable guidance for its experimental applications to electronics and optoelectronics. PMID- 26538041 TI - Probing Photocurrent Generation, Charge Transport, and Recombination Mechanisms in Mesostructured Hybrid Perovskite through Photoconductivity Measurements. AB - Conductivity of methylammonium lead triiodide (MAPbI3) perovskite was measured on different mesoporous metal oxide scaffolds: TiO2, Al2O3, and ZrO2, as a function of incident light irradiation and temperature. It was found that MAPbI3 exhibits intrinsic charge separation, and its conductivity stems from a majority of free charge carriers. The crystal morphology of the MAPbI3 was found to significantly affect the photoconductivity, whereas in the dark the conductivity is governed by the perovskite in the pores of the mesoporous scaffold. The temperature-dependent conductivity measurements also indicate the presence of states within the band gap of the perovskite. Despite a relatively large amount of crystal defects in the measured material, the main recombination mechanism of the photogenerated charges is bimolecular (band-to-band), which suggests that the defect states are rather inactive in the recombination. This may explain the remarkable efficiencies obtained for perovskite solar cells prepared with wet-chemical methods. PMID- 26538042 TI - Softening upon Adsorption in Microporous Materials: A Counterintuitive Mechanical Response. AB - We demonstrate here that microporous materials can exhibit softening upon adsorption of guest molecules, at low to intermediate pore loading, in parallel to the pore shrinking that is well-known in this regime. This novel and counterintuitive mechanical response was observed through molecular simulations of both model pore systems (such as slit pore) and real metal-organic frameworks. It is contrary to common belief that adsorption of guest molecules necessarily leads to stiffening due to increased density, a fact that we show is the high loading limit of a more complex behavior: a nonmonotonic softening-then stiffening. PMID- 26538043 TI - A "Tips and Tricks" Practical Guide to the Synthesis of Gold Nanorods. PMID- 26538044 TI - Ligand Surface Chemistry Dictates Light Emission from Nanocrystals. AB - There are several contradictory accounts of the changes to the emissive behavior of semiconductor nanocrystal upon a ligand exchange from trioctylphosphine/cadmium-phosphonates passivation to N-butylamine. This communication explains the contradictory accounts of this reaction using new insights into ligand chemistry. Also, a previously unknown link between surface emission and cadmium-phosphonate (Z-type) ligands is shown. PMID- 26538045 TI - Investigation of Bismuth Triiodide (BiI3) for Photovoltaic Applications. AB - Guided by predictive discovery framework, we investigate bismuth triiodide (BiI3) as a candidate thin-film photovoltaic (PV) absorber. BiI3 was chosen for its optical properties and the potential for "defect-tolerant" charge transport properties, which we test experimentally by measuring optical absorption and recombination lifetimes. We synthesize phase-pure BiI3 thin films by physical vapor transport and solution processing and single-crystals by an electrodynamic gradient vertical Bridgman method. The bandgap of these materials is ~1.8 eV, and they demonstrate room-temperature band-edge photoluminescence. We measure monoexponential recombination lifetimes in the range of 180-240 ps for thin films, and longer, multiexponential dynamics for single crystals, with time constants up to 1.3 to 1.5 ns. We discuss the outstanding challenges to developing BiI3 PVs, including mechanical and electrical properties, which can also inform future selection of candidate PV absorbers. PMID- 26538046 TI - Raman Measurements of Pure Hydrogen Clathrate Formation from a Supercooled Hydrogen-Water Solution. AB - The nucleation and growth of a solid clathrate hydrate from the liquid phase is a process that is even less understood and more difficult to study than the nucleation of a solid phase from a pure liquid. We have employed in situ Raman spectroscopy to study the hydrogen-water supercooled solution undergoing clathrate formation at a pressure of about 2 kbar and temperature of 263 K. Raman light scattering detects unambiguously the H2 molecules inside of clathrate crystallites, which change stoichiometry during growth. The spectral intensity of the hydrogen vibrational band shows the time evolution of the population of the large and small cages, demonstrating that, in the initial stages of clathrate formation, the occupation of the large cages is quite lower than its equilibrium value. From the measurement of the growth rate of the crystallites, we demonstrate that the growth of the clathrate in the liquid is a diffusion-limited process. PMID- 26538047 TI - Carr-Purcell Pulsed Electron Double Resonance with Shaped Inversion Pulses. AB - Pulsed electron paramagnetic resonance (EPR) spectroscopy allows the determination of distances, in the range of 1.5-8 nm, between two spin-labels attached to macromolecules containing protons. Unfortunately, for hydrophobic lipid-bound or detergent-solubilized membrane proteins, the maximum distance accessible is much lower, because of a strongly reduced coherence time of the electron spins. Here we introduce a pulse sequence, based on a Carr-Purcell decoupling scheme on the observer spin, where each pi-pulse is accompanied by a shaped sech/tanh inversion pulse applied to the second spin, to overcome this limitation. This pump/probe excitation scheme efficiently recouples the dipolar interaction, allowing a substantially longer observation time window to be achieved. This increases the upper limit and accuracy of distances that can be determined in membrane protein complexes. We validated the method on a bis nitroxide model compound and applied this technique to the trimeric betaine transporter BetP. Interprotomer distances as long as 6 nm could be reliably determined, which is impossible with the existing methods. PMID- 26538048 TI - Evidence in Support of Exciton to Ligand Vibrational Coupling in Colloidal Quantum Dots. AB - The Perspective focuses on the investigation of an unresolved conflict in semiconductor colloidal quantum dots (CQDs) research, concerning the influence of the immediate surrounding on the optical properties of the materials. Today's advanced synthetic colloidal procedures offer formation of a high-quality inorganic crystallite, capped with various organic/inorganic molecular ligands. The Perspective aims to clarify whether exciton recombination processes in CQDs are influenced by the type of crystallite-ligand bonding and, moreover, whether these excitonic processes experience direct coupling to the ligands' vibrational modes. Most ligands used have redox characteristics whose functional groups are added on to the CQDs' surface via coordination, covalent or ionic bonding. The surface-ligand bonding introduces electronic states either above or below the intraband/interband energy gap, resulting in electronic passivation or in creation of trapping states that affect intraband and interband relaxation processes. Furthermore, crystalline electronic states may have a direct coupling to molecular vibrational states via direct overlap of electronic wave functions or through a long-range energy-transfer process. Also, photoejected carriers resulting from an Auger process or ionization processes may diffuse temporarily onto a ligand site. These scenarios are discussed in the current publication with supporting theoretical and experimental observations. PMID- 26538049 TI - Transition from the Tetragonal to Cubic Phase of Organohalide Perovskite: The Role of Chlorine in Crystal Formation of CH3NH3PbI3 on TiO2 Substrates. AB - The role of chlorine in the superior electronic property and photovoltaic performance of CH3NH3PbI(3-x)Clx perovskite has attracted recent research attention. Here, we study the impact of chlorine in the perspective of the crystal structure of the perovskite layer, which can provide important understanding of its excellent charge mobility and extended lifetimes. In particular, we find that in the presence of chlorine (PbCl2 or CH3NH3Cl), when CH3NH3PbI3 films are deposited on a TiO2 mesoporous layer instead of a planar TiO2 substrate, a stable cubic phase rather than the commonly observed tetragonal phase is formed in CH3NH3PbI3 perovskite at room temperature. The relative peak intensity of two major facets of cubic CH3NH3PbI3 crystals, (100)C and (200)C facets, can also be easily tuned, depending on the film thickness. Furthermore, compared with pristine CH3NH3PbI3 perovskite films, in the presence of chlorine, CH3NH3PbI3 crystals grown on planar substrates exhibit strong preferred orientations on (110)T and (220)T facets. PMID- 26538050 TI - Low-Scaling Quantum Chemistry Approach to Excited-State Properties via an ab Initio Exciton Model: Application to Excitation Energy Transfer in a Self Assembled Nanotube. AB - We introduce a charge-embedding scheme for an excited-state quantum chemistry method aimed at weakly interacting molecular aggregates. The Hamiltonian matrix for the aggregate is constructed in a basis of direct products of configuration state functions for the monomers, and diagonalization of this matrix affords excitation energies within ~0.2 eV of the corresponding supersystem calculation. Both the basis states and the coupling matrix elements can be computed in a distributed way, resulting in an algorithm whose time-to-solution is independent of the number of chromophores, and we report calculations on systems with almost 55 000 basis functions using fewer than 450 processors. In a semiconducting organic nanotube, we find evidence of ultrafast, coherent dynamics followed by energy localization driven by static disorder. Truncation of the model system has a qualitative effect on the energy-transfer dynamics, demonstrating the importance of simulating an extended portion of the nanotube, which is not feasible using traditional quantum chemistry. PMID- 26538051 TI - Direct Observation of Triplet-State Population Dynamics in the RNA Uracil Derivative 1-Cyclohexyluracil. AB - Investigation of the excited-state dynamics in nucleic acid monomers is an area of active research due to the crucial role these early events play in DNA and RNA photodamage. The dynamics and rate at which the triplet state is populated are key mechanistic pathways yet to be fully elucidated. Direct spectroscopic evidence is presented in this contribution for intersystem crossing dynamics in a uracil derivative, 1-cyclohexyluracil. It is shown that intersystem crossing to the triplet manifold occurs in one picosecond or less in acetonitrile solution-at least an order of magnitude faster than previously estimated experimentally. Broadband transient absorption measurements also reveal the primary electronic relaxation pathways of the uracil chromophore, including the absorption spectra of the (1)pipi*, (1)npi*, and (3)pipi* states and the rates of vibrational cooling in the ground and (3)pipi* states. The experimental results are supported by density functional calculations. PMID- 26538052 TI - Hydrostatic Pressure Promotes Domain Formation in Model Lipid Raft Membranes. AB - Neutron diffraction measurements demonstrate that hydrostatic pressure promotes liquid-ordered (Lo) domain formation in lipid membranes prepared as both oriented multilayers and unilamellar vesicles made of a canonical ternary lipid mixture for which demixing transitions have been extensively studied. The results demonstrate an unusually large dependence of the mixing transition on hydrostatic pressure. Additionally, data at 28 degrees C show that the magnitude of increase in Lo caused by 10 MPa pressure is much the same as the decrease in Lo produced by twice minimum alveolar concentrations (MAC) of general anesthetics such as halothane, nitrous oxide, and xenon. Therefore, the results may provide a plausible explanation for the reversal of general anesthesia by hydrostatic pressure. PMID- 26538053 TI - Some Interesting Properties and Promising Applications of Nanostructured Materials. PMID- 26538054 TI - Apoptosis-like cell death induced by nematocyst venom from Chrysaora helvola Brandt jellyfish and an in vitro evaluation of commonly used antidotes. AB - The present work investigated the in vitro cytotoxicity of nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish against human MCF-7 and CNE 2 tumor cell lines. Potent cytotoxicity was quantified using the MTT assay (LC50=12.07+/-3.13 and 1.6+/-0.22MUg/mL (n=4), respectively). Apoptosis-like cell death was further confirmed using the LDH release assay and Annexin V/PI double staining-based flow cytometry analysis. However, only activation of caspase-4 was observed. It is possible that some caspase-independent pathways were activated by the NV treatment. Since no reference or antivenom is available, the effects of several commonly used antidotes on the cytotoxicity of NV were examined on more sensitive CNE-2 cells to determine the appropriate emergency measures for envenomation by C. helvola. The phospholipase A2 (PLA2) inhibitor para bromophenacyl bromide (pBPB) showed no protective effect, while Mg(2+) potentiated cytotoxicity. Voltage-gated L-type Ca(2+) channel blockers (verapamil, nifedipine and felodipine) and Na-Ca(2+) exchanger inhibitor KB-R7943 also showed no effect. Assays using Ca(2+)-free culture media or the intracellular Ca(2+) chelator BAPTA also could not inhibit the cytotoxicity. Taken together, these results suggest that PLA2 and Ca(2+) are not directly involved in the cytotoxicity of NV from C. helvola. Our work also suggests caution regarding the choice for first aid for envenomation by C. helvola jellyfish. PMID- 26538055 TI - Parental Predictors of Children's Shame and Guilt at Age 6 in a Multimethod, Longitudinal Study. AB - Shame and guilt are self-conscious emotions that begin to develop early in life and are associated with various forms of psychopathology. However, little is known about the factors that contribute to these emotions in young children. Specifically, no longitudinal studies to date have examined a range of parent factors that shape the expression of children's shame and guilt. The current multimethod, longitudinal study sought to determine whether parenting style, parental psychopathology, and parents' marital satisfaction assessed when children were age 3 predict expressions of shame and guilt in children at age 6. A large community sample of families (N = 446; 87.4% Caucasian) with 3-year-old children (45.7% female) was recruited through commercial mailing lists. Parent variables were assessed when children were age 3 with mother- and father-report questionnaires and a diagnostic interview. Children's expressions of shame and guilt were observed in the laboratory at age 6. Fathers', but not mothers', history of depression and permissive parenting assessed when children were age 3 predicted children's expressions of shame and guilt when children were age 6; parents' marital dissatisfaction also predicted children's shame and guilt. These findings suggest that parents, and fathers in particular, contribute to expressions of self-conscious emotions in children. These data on emotional development may be useful for better characterizing the risk and developmental pathways of psychopathology. PMID- 26538057 TI - Editor's Note. PMID- 26538056 TI - Seasons of Risk: Anticipated Behavior on Vacation and Interest in Episodic Antiretroviral Pre-exposure Prophylaxis (PrEP) Among a Large National Sample of U.S. Men Who have Sex with Men (MSM). AB - The current analysis evaluates interest in and acceptability of daily PrEP during short episodes of anticipated increased risk (i.e. Epi-PrEP). In 2013, U.S. members of an internet-based MSM sexual networking site were invited to complete a survey about HIV prevention practices in the context of vacationing. 7305 MSM responded to the survey. Of respondents who had vacationed in the past year, 25.6 % reported condomless anal sex (CAS) with new male sex partners while vacationing. Most (92.6 %) respondents agreed that having to use PrEP every day was a barrier to PrEP use and 74.3 % indicated they would take PrEP if they knew it would be helpful for short periods of anticipated increased risk. MSM who reported increased CAS while on vacation in the past year were more likely to indicate that they would take PrEP if it were helpful when used for short periods than respondents who did not (aOR = 2.02, 95 % CI 1.59-2.56, p < 0.001). Studies designed to evaluate uptake, adherence, and protective benefit of short PrEP courses are warranted. PMID- 26538058 TI - Bugs and Guts: Practical Applications of Probiotics for Gastrointestinal Disorders in Children. AB - Probiotics are foods or products that contain live microorganisms that benefit the host when administered. In this clinical review, we evaluate the literature associated with using probiotics in common pediatric gastrointestinal disorders, focusing specifically on antibiotic-associated diarrhea, acute gastroenteritis, Clostridium difficile infection (CDI), colic, inflammatory bowel disease, and functional gastrointestinal diseases. Meta-analysis of several randomized controlled trials have confirmed benefit for the administration of Lactobacillus rhamnosus GG and Saccharomyces boulardii to prevent antibiotic-associated diarrhea and to treat acute infectious diarrhea. Individual studies have also suggested benefit of probiotics to prevent acute gastroenteritis and serve as an adjunct in ulcerative colitis, pouchitis, antibiotic-associated diarrhea, CDI, functional abdominal pain, irritable bowel syndrome, and colic in breastfed babies. Although promising, larger well-designed studies need to confirm these findings. There is currently insufficient evidence to recommend probiotics for the treatment of constipation-predominant irritable bowel syndrome or Crohn's disease. PMID- 26538059 TI - PRO-viding Additional Evidence for Enteral Nutrition in Septic Shock. PMID- 26538060 TI - Pros and Cons of Feeding the Septic Intensive Care Unit Patient: Response to Patel et al. PMID- 26538061 TI - Wernicke Encephalopathy: A "Complication" of Acute Liver Failure. PMID- 26538062 TI - Physiological implications of the abnormal absence of the parietal foramen in a late Permian cynodont (Therapsida). AB - The third eye (pineal eye), an organ responsible for regulating exposure to sunlight in extant ectotherms, is located in an opening on the dorsal surface of the skull, the parietal foramen. The parietal foramen is absent in extant mammals but often observed in basal therapsids, the stem-group to true mammals. Here, we report the absence of the parietal foramen in a specimen of Cynosaurus suppostus, a Late Permian cynodont from South Africa (SA). Comparison with Procynosuchus delaharpeae, a contemporaneous non-mammalian cynodont from SA, demonstrates that the absence of this foramen is an abnormal condition for such a basal species. Because seasonality was marked during the Late Permian in SA, it is proposed that the third eye was functionally redundant in Cynosaurus, possibly due to the acquisition of better thermoregulation or the evolution of specialized cells in the lateral eyes to compensate for the role of the third eye. PMID- 26538063 TI - Calcium and vitamin D nutrition and bisphosphonate treatment. PMID- 26538064 TI - CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs. AB - Current antiretroviral therapy does not eliminate the integrated and transcriptionally silent HIV-1 provirus in latently infected cells. Recently, a "shock and kill" strategy has been extensively explored to eradicate the HIV-1 latent reservoirs for a permanent cure of AIDS. The therapeutic efficacy of currently used agents remains disappointing because of low efficiency, non specificity and cellular toxicity. Here we present a novel catalytically deficient Cas9-synergistic activation mediator (dCas9-SAM) technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. By screening 16 MS2-mediated single guide RNAs, we identified long terminal repeat (LTR)-L and O that surround the enhancer region (-165/-145 for L and -92/-112 for O) and induce robust reactivation of HIV-1 provirus in HIV-1 latent TZM-bI epithelial, Jurkat T lymphocytic and CHME5 microglial cells. This compulsory reactivation induced cellular suicide via toxic buildup of viral proteins within HIV-1 latent Jurkat T and CHME5 microglial cells. These results suggest that this highly effective and target-specific dCas9-SAM system can serve as a novel HIV latency-reversing therapeutic tool for the permanent elimination of HIV-1 latent reservoirs. PMID- 26538065 TI - Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Qbeta, and the Induction of Anticancer Antibodies. AB - The development of carbohydrate-based antitumor vaccines is an attractive approach towards tumor prevention and treatment. Herein, we focused on the ganglioside GM2 tumor-associated carbohydrate antigen (TACA), which is overexpressed in a wide range of tumor cells. GM2 was synthesized chemically and conjugated with a virus-like particle derived from bacteriophage Qbeta. Although the copper-catalyzed azide-alkyne cycloaddition reaction efficiently introduced 237 copies of GM2 per Qbeta, this construct failed to induce significant amounts of anti-GM2 antibodies compared to the Qbeta control. In contrast, GM2 immobilized on Qbeta through a thiourea linker elicited high titers of IgG antibodies that recognized GM2-positive tumor cells and effectively induced cell lysis through complement-mediated cytotoxicity. Thus, bacteriophage Qbeta is a suitable platform to boost antibody responses towards GM2, a representative member of an important class of TACA: the ganglioside. PMID- 26538066 TI - Gene-expression patterns in peripheral blood classify familial breast cancer susceptibility. AB - BACKGROUND: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC. METHODS: We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers. RESULTS: Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk. CONCLUSIONS: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk. PMID- 26538067 TI - Prevalence and genotypic characterization of Human Parvovirus B19 in children with measles- and rubella-like illness in Iran. AB - Human Parvovirus B19 (B19V) is a prototype of the Erythroparvovirus genus in Parvoviridae family. B19V infections are often associated with fever and rash, and can be mistakenly reported as measles or rubella. Differential diagnosis of B19V illness is necessary for case management and also for public health control activities, particularly in outbreak situations in which measles or rubella is suspected. To investigate the causative role of B19V infection in children with measles- and rubella-like illness, a total of 583 sera from children with exanthema were tested for presence of B19V by determining anti-B19V IgG and IgM antibodies by ELISA as well as B19V DNA detection by nested PCR. DNA positive samples were assessed further for determination of viral load and sequence analysis by Real-Time PCR and Sanger sequencing method, respectively. Out of 583 patients, 112 (19.21%) patients were positive for B19V-IgM antibody, 110 (18.87%) were positive for B19V-IgG antibody, and 63 (10.81%) were positive for B19V viral DNA. The frequency of B19V-IgG antibodies were increased with age; that is children under 6 year old showed 7.11% seroprevalence for B19V-IgG as compared to 18.39% and 28.91% for age groups 6 to >11 and 11-14 years old, respectively. Phylogenetic analysis of the NS1-VPu1 overlapping region revealed that all sequenced B19V-DNA belonged to genotype 1. The results of this study may aid the surveillance programs aiming at eradicating measles/rubella virus in Iran, as infections with B19V can be mistakenly reported as measles or rubella if laboratory testing is not conducted. PMID- 26538068 TI - Herpesvirus orthologues of CD200 bind host CD200R but not related activating receptors. AB - Several herpesviruses have acquired the gene for the CD200 membrane protein from their hosts and can downregulate myeloid activity through interaction of this viral CD200 orthologue with the host receptor for CD200, namely CD200R, which can give inhibitory signals. This receptor is a 'paired receptor', meaning proteins related to the inhibitory CD200R are present but differ in that they can give activating signals and also give a negligible interaction with CD200. We showed that the viral orthologues e127 from rat cytomegalovirus and K14 from human herpesvirus 8 do not bind the activating CD200R-like proteins from their respective species, although they do bind the inhibitory receptors. It is thought that the activating receptors have evolved in response to pathogens targeting the inhibitory receptor. In this case, the CD200 orthologue is not trapped by the activating receptor but has maintained the specificity of the host from which it was acquired, suggesting that the activating members of the CD200R family have evolved to protect against a different pathogen. PMID- 26538069 TI - Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population. AB - Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT-DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA-cleared Illumina MiSeqDx CF 139-Variant Assay (139-VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139-VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139-VA. Sixty three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39-mutation InPlex panel), up to 86.0% for the 139-VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139-VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139-VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening. PMID- 26538072 TI - Prospective Cohort Studies. PMID- 26538070 TI - Length of stay an important mediator of hospital-acquired methicillin-resistant Staphylococcus aureus. AB - Hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is becoming increasingly established in Asian hospitals. The primary aim of this study was to decompose the risk factors for HA-MRSA based on conceptual clinical pathways. The secondary aim was to show the amount of effect attributable to antibiotic exposure and total length of stay before outcome (LBO) so that institutions can manage at-risk patients accordingly. A case-control study consisting of 1200 inpatients was conducted in a large tertiary hospital in Singapore between January and December 2006. Results from the generalized structural equation model (GSEM) show that LBO [adjusted odds ratio (aOR) 14.9, 95% confidence interval (CI) 8.7-25.5], prior hospitalization (aOR 6.2, 95% CI 3.3-11.5), and cumulative antibiotic exposure (aOR 3.5, 95% CI 2.3-5.3), directly affected HA-MRSA acquisition. LBO accounted for the majority of the effects due to age (100%), immunosuppression (67%), and surgery (96%), and to a lesser extent for male gender (22%). Our model enabled us to account and quantify effects of intermediaries. LBO was found to be an important mediator of age, immunosuppression and surgery on MRSA infection. Traditional regression approaches will not only give different conclusions but also underestimate the effects. Hospitals should minimize the hospital stay when possible to reduce the risk of MRSA. PMID- 26538073 TI - UC Davis Transgenic Animal Research Conference X (TARC X): Tahoe City, CA, USA, August 9-12, 2015. PMID- 26538074 TI - Exercise as Therapy for Diabetic and Prediabetic Neuropathy. AB - Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function. PMID- 26538075 TI - The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis. AB - PURPOSE: The objective of this systematic review was to assess the effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects. METHODS: The search process was based on the selection of publications (DB-RCT and RCT) listed in the following databases: PubMed, Web of Knowledge, Scopus, the Cochrane Library and Embase. To assess the study quality, a nine-point scoring system according to the Newcastle-Ottawa scale was used, and a high-quality study was defined by a threshold of >=7 points. Thirteen randomized controlled trials were included. The analysed population consisted of 1955 overweight and obese subjects. The mean age ranged from 13.6 to 71.7 years. Changes in the concentration of 25-hydroxycholecalciferol (25(OH)D), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) were assessed. To combine individual study results, a meta-analysis was performed. RESULTS: The baseline levels of 25(OH)D suggested vitamin D deficiency or insufficiency in the analysed population. The vitamin D supplementation did not influence on CRP (std. mean differences -0.11; 95 % CI -0.27-0.04; p = 0.15), TNF-alpha (std. mean differences -0.13; 95 % CI -0.38-0.12; p = 0.31) and IL-6 concentrations (std. mean differences 0.1; 95 % CI -0.43-0.63; p = 0.71). CONCLUSIONS: This meta-analysis suggests that supplementation with vitamin D does not have a significant influence on changes in the concentration of selected inflammatory biomarkers in the obese and overweight subjects. PMID- 26538076 TI - Disseminated mucormycosis with myocardial involvement in a renal transplant recipient. AB - We report the case of a renal transplant recipient with pulmonary and splenic mucormycosis whose demise was accelerated by a myocardial abscess. Once pulmonary and splenic mucormycosis was diagnosed, liposomal amphotericin B was started and immunosuppressant treatments were discontinued. The pulmonary cavities regressed during treatment, but new myocardial and peri-allograft abscesses developed. The myocardial abscess diffusely infiltrated the left ventricular wall and was associated with akinesia, which led to sudden cardiac arrest. This case demonstrates a rare manifestation of mucormycosis and highlights the fatality and invasiveness of this infection. PMID- 26538078 TI - Role of magnifying colonoscopy for diagnosis of colorectal neoplasms: From the perspective of Japanese colonoscopists. AB - Colorectal cancer is the third leading cause of cancer-related death. As the therapeutic strategy for colorectal cancer depends on the clinical stage of the tumor, precise and accurate staging is necessary prior to treatment decision making. Colonoscopy is an essential tool for detection and prevention of colorectal cancer, as it also allows for removal of adenomatous lesions. Using conventional endoscopy, however, it is sometimes difficult to differentiate neoplastic lesions from non-neoplastic lesions. Several new endoscopic technologies have been developed to provide a more precise diagnosis. Magnifying chromoendoscopy and narrow-band imaging endoscopy with or without magnification are invaluable not only for distinction of colorectal neoplastic lesions from non neoplastic lesions, but also for the accurate diagnosis of invasion depth in colorectal cancers. Based on an accumulation of a large number of clinical data, the use of magnifying colonoscopy has become inevitable for the prediction of histology and the diagnosis of invasion depth of colorectal neoplasms in Japan. PMID- 26538077 TI - Detection of palisade vessels as a landmark for Barrett's esophagus in a Western population. AB - BACKGROUND: In Japan, palisade vessels (PV) are used to distinguish the esophagogastric junction (EGJ). Elsewhere, the EGJ is defined by the upper end of the gastric folds (GF) and PV are considered difficult to detect. This study evaluated the detection rate of PV in Western patients with Barrett's esophagus (BE) using white light imaging (WLI) and narrow band imaging (NBI), and quantified any discordance between Western and Japanese criteria for the EGJ. METHODS: In 25 BE patients, the presence and location of PV and GF were determined and biopsies were obtained. High-quality images of the EGJ were collected under different conditions (insufflations-desufflation, WLI-NBI, forward-retroflex approach), resulting in eight different images per patient. The presence of PV on each still image was assessed by a panel of six Western and Japanese endoscopists with expertise in BE. RESULTS: PV were observed in >= 1 images by a majority of the panel (>= 4 raters) in 100 % of patients during insufflation versus 60 % during desufflation (p < 0.001). WLI and NBI detected PV in 100 and 92 %, respectively (p = 0.50). Interobserver agreement of the panel was 'moderate' (kappa = 0.51). During endoscopy PV were located a median of 1 cm distal of the GF in 15 patients (63 %), with intestinal metaplasia (IM) in this discordant zone, in 27 % of patients. CONCLUSIONS: PV are visible in most Western BE patients and are best inspected during insufflation. The location of the GF and PV differed in a substantial group of patients, partially with IM in this discordant zone. PMID- 26538079 TI - Curvature-based interaction potential between a micro/nano curved surface body and a particle on the surface of the body. AB - The interaction potential between a curved surface body and a particle located on the surface of the body is studied in this paper. Based on the negative exponential pair potential (1/R(n)) between particles, the interaction potential is proved to be of the curvature-based form, i.e., it can be written as a function of curvatures of the surface. Idealized numerical experiments are designed to test the accuracy of curvature-based potential. Based on the curvature-based potential, propositions below are confirmed: a highly curved surface body will induce driving forces on the particle located on the surface, and curvatures and the gradients of curvatures are essential factors forming the driving forces. In addition, the tangent driving force acting on the particle from the curved surface body is studied. Based on duality, the following rule is proved: for a convex or concave curved body sharing the same curved surface, the curvature-based interaction potential between them and a particle on the surface can make up the potential of a particle in the whole space. PMID- 26538080 TI - The asymmetric total synthesis of (+)-N-acetyl norloline. AB - The asymmetric total synthesis of (+)-N-acetyl norloline, the putative biogenic precursor of all known loline alkaloids, has been achieved in 12 steps from commercially available (R)-glyceraldehyde acetonide. The synthesis relies on the Rassu/Casiraghi's vinylogous aldol reaction, an intramolecular oxa heteroconjugate addition and a reductive amination to establish the four contiguous stereogenic centers and construct the strained oxygen-bridge under mild conditions. PMID- 26538081 TI - Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats. AB - Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders. PMID- 26538082 TI - Identifying the content of home-based health behaviour change interventions for frail older people: a systematic review protocol. AB - BACKGROUND: Meeting the needs of the growing number of older people is a challenge for health and social care services. Home-based interventions aiming to modify health-related behaviours of frail older people have the potential to improve functioning and well-being. Previous reviews have focused on whether such interventions are effective, rather than what might make them effective. Recent advances in behavioural science make possible the identification of potential 'active ingredients' of effective interventions, such as component behaviour change techniques (BCTs), and intended intervention functions (IFs; e.g. to educate, to impart skills). This paper reports a protocol for a systematic review that seeks to (a) identify health behaviour change interventions for older frail people, (b) describe the content of these interventions, and (c) explore links between intervention content and effectiveness. The protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses Protocols (PRISMA-P) 2015 guidelines. METHODS/DESIGN: Studies will be identified through a systematic search of 15 electronic databases, supplemented by citation tracking. Studies will be retained for review where they report randomised controlled trials focusing on home-based health promotion delivered by a health professional for frail older people in community settings, written in English, and either published from 1980 onwards, or, for registered trials only, unpublished but completed with results obtainable from authors. Interventions will be coded for their content (BCTs, IFs) and for evidence of effectiveness (outcome data relating to behavioural and health outcomes). Analyses will describe characteristics of all interventions. Interventions for which effectiveness data are available will be categorised into those showing evidence of effectiveness versus those showing no such evidence. The potential for each intervention characteristic to contribute to change in behaviour or health outcomes will be estimated by calculating the percentage of all interventions featuring those characteristics that have shown effectiveness. DISCUSSION: Results will reveal the strategies that have been drawn on within home-based interventions to modify the health behaviours of frail older people, and highlight those more associated with positive changes in behaviour and health. Findings from this review will provide a useful basis for understanding, developing, and implementing behaviour change interventions in this field. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010370. PMID- 26538083 TI - OECD rates quality of UK healthcare as worse than in many similar countries. PMID- 26538084 TI - Losing women along the path to safe motherhood: why is there such a gap between women's use of antenatal care and skilled birth attendance? A mixed methods study in northern Uganda. AB - BACKGROUND: Thousands of women and newborns still die preventable deaths from pregnancy and childbirth-related complications in poor settings. Delivery with a skilled birth attendant is a vital intervention for saving lives. Yet many women, particularly where maternal mortality ratios are highest, do not have a skilled birth attendant at delivery. In Uganda, only 58 % of women deliver in a health facility, despite approximately 95 % of women attending antenatal care (ANC). This study aimed to (1) identify key factors underlying the gap between high rates of antenatal care attendance and much lower rates of health-facility delivery; (2) examine the association between advice during antenatal care to deliver at a health facility and actual place of delivery; (3) investigate whether antenatal care services in a post-conflict district of Northern Uganda actively link women to skilled birth attendant services; and (4) make recommendations for policy- and program-relevant implementation research to enhance use of skilled birth attendance services. METHODS: This study was carried out in Gulu District in 2009. Quantitative and qualitative methods used included: structured antenatal care client entry and exit interviews [n = 139]; semi structured interviews with women in their homes [n = 36], with health workers [n = 10], and with policymakers [n = 10]; and focus group discussions with women [n = 20], men [n = 20], and traditional birth attendants [n = 20]. RESULTS: Seventy five percent of antenatal care clients currently pregnant reported they received advice during their last pregnancy to deliver in a health facility, and 58 % of these reported having delivered in a health facility. After adjustment for confounding, women who reported they received advice at antenatal care to deliver at a health facility were significantly more likely (aOR = 2.83 [95 % CI: 1.19 6.75], p = 0.02) to report giving birth in a facility. Despite high antenatal care coverage, a number of demand and supply side barriers deter use of skilled birth attendance services. Primary barriers were: fear of being neglected or maltreated by health workers; long distance and other difficulties in access; poverty, and material requirements for delivery; lack of support from husband/partner; health systems deficiencies such as inadequate staffing/training, work environment, and referral systems; and socio-cultural and gender issues such as preferred birthing position and preference for traditional birth attendants. CONCLUSIONS: Initiatives to improve quality of client-provider interaction and respect for women are essential. Financial barriers must be abolished and emergency transport for referrals improved. Simultaneously, supply side barriers must be addressed, notably ensuring a sufficient number of health workers providing skilled obstetric care in health facilities and creating habitable conditions and enabling environments for them. PMID- 26538085 TI - Soft resonator of omnidirectional resonance for acoustic metamaterials with a negative bulk modulus. AB - Monopolar resonance is of fundamental importance in the acoustic field. Here, we present the realization of a monopolar resonance that goes beyond the concept of Helmholtz resonators. The balloon-like soft resonator (SR) oscillates omnidirectionally and radiates from all parts of its spherical surface, eliminating the need for a hard wall for the cavity and baffle effects. For airborne sound, such a low-modulus resonator can be made extremely lightweight. Deep subwavelength resonance is achieved when the SR is tuned by adjusting the shell thickness, benefiting from the large density contrast between the shell material and the encapsulated gas. The SR resonates with near-perfect monopole symmetry, as demonstrated by the theoretical and experimental results, which are in excellent agreement. For a lattice of SRs, a band gap occurs and blocks near total transmission, and the effective bulk modulus exhibits a prominent negative band, while the effective mass density remains unchanged. Our study shows that the SR is suitable for building 3D acoustic metamaterials and provides a basis for constructing left-handed materials as a new means of creating a negative bulk modulus. PMID- 26538086 TI - Improving chemotherapeutic efficiency in acute myeloid leukemia treatments by chemically synthesized peptide interfering with CXCR4/CXCL12 axis. AB - Bone marrow stroma can protect acute myeloid leukemia (AML) cells against chemotherapeutic agents and provide anti-apoptosis and chemoresistance signals through secreting chemokine CXCL12 to activate its receptor CXCR4 on AML cells, resulting in minimal residual leukemia and relapse. Therefore disrupting the CXCR4/CXCL12 axis with antagonists is of great significance for improving chemosensitivity and decreasing relapse rate. In a previous study, we reported a novel synthetic peptide E5 with its remarkable effect on inhibiting CXCR4/CXCL12 mediated adhesion and migration of AML cells. Here we presented E5's capacity of enhancing the therapeutic efficiency of various chemotherapeutics on AML in vitro and in vivo. Results showed that E5 can diminish bone marrow stromal cell provided protection to leukemia cells, significantly increasing the apoptosis induced by various chemotherapeutics in multiple AML cell lines. In an AML mouse xenograft model, E5 induced 1.84-fold increase of circulating AML cells out of protective stroma niche. Combined with vincristine or cyclophosphamide, E5 inhibited infiltration of AML cells into bone marrow, liver and spleen, as well as prolonged the lifespan of AML mice compared with mice treated with chemotherapy alone. In addition, E5 presented no toxicity in vivo according to the histological analysis and routine clinical parameters of serum analysis. PMID- 26538087 TI - Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability-high phenotype. AB - The relevance of the clinicopathological and molecular features of early gastric cancers (EGCs) having the microsatellite instability (MSI)-high phenotype has not been clearly defined in sporadic gastric carcinogenesis. Here, we examined the clinicopathological and molecular characteristics of EGC according to MSI status in 330 patients with EGC (intestinal-type adenocarcinoma). Tumors were classified as MSI-high (45 cases), MSI-low (9 cases), or microsatellite stable (MSS; 276 cases). The specimens were examined using a combination of polymerase chain reaction (PCR)-microsatellite assays and PCR-pyrosequencing to detect chromosomal allelic imbalances in multiple cancer-related chromosomal loci, MSI, gene mutations (KRAS and BRAF) and methylation status [high methylation epigenome (HME), intermediate methylation epigenome and low methylation epigenome]. In addition, the expression levels of various target proteins were examined using immunohistochemistry. Interestingly, EGC with the MSI phenotype showed distinct papillary features. The expression of gastric mucin was more frequent in EGC with the MSI phenotype, while p53 overexpression was common in EGCs, irrespective of MSI status. The frequency of HME was significantly higher in EGCs with the MSI phenotype than in EGCs with the MSS phenotype. Although there was a low frequency of allelic imbalance in EGCs with the MSI phenotype, some markers of allelic imbalance were more frequently detected in EGCs with the MSI-high phenotype than in EGCs with the MSS phenotype. KRAS and BRAF mutations were rare in EGCs. Thus, the MSI phenotype in EGC is a major precursor lesion in gastric cancer and is characterized by distinct clinicopathological and molecular features. PMID- 26538088 TI - Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model. AB - Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 +/- 86 million nucleated cells and 29,030 +/- 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 +/- 42 million nucleated cells and 30,266 +/- 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone regeneration response that approaches the limits of performance that can be achieved in the CFMD model. Further advancement and comparison of these intraoperative bone marrow cell processing methods will require use of a larger and more biologically compromised defect site to guide the next steps of preclinical development and optimization. PMID- 26538089 TI - Ankyrin-B directs membrane tethering of periaxin and is required for maintenance of lens fiber cell hexagonal shape and mechanics. AB - Periaxin (Prx), a PDZ domain protein expressed preferentially in myelinating Schwann cells and lens fibers, plays a key role in membrane scaffolding and cytoarchitecture. Little is known, however, about how Prx is anchored to the plasma membrane. Here we report that ankyrin-B (AnkB), a well-characterized adaptor protein involved in linking the spectrin-actin cytoskeleton to integral membrane proteins, is required for membrane association of Prx in lens fibers and colocalizes with Prx in hexagonal fiber cells. Under AnkB haploinsufficiency, Prx accumulates in the soluble fraction with a concomitant loss from the membrane enriched fraction of mouse lenses. Moreover, AnkB haploinsufficiency induced age dependent disruptions in fiber cell hexagonal geometry and radial alignment and decreased compressive stiffness in mouse lenses parallel to the changes observed in Prx null mouse lens. Both AnkB- and Prx-deficient mice exhibit disruptions in membrane organization of the spectrin-actin network and the dystrophin glycoprotein complex in lens fiber cells. Taken together, these observations reveal that AnkB is required for Prx membrane anchoring and for maintenance of lens fiber cell hexagonal geometry, membrane skeleton organization, and biomechanics. PMID- 26538091 TI - More roles for the (passive) giant. Focus on "The increase in non-cross-bridge forces after stretch of activated striated muscle is related to titin isoforms". PMID- 26538090 TI - The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. AB - The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22alpha promoter (SM22alpha-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive (SM22alpha)CaSR(Deltaflox/Deltaflox) [knockout (KO)] mice showed an endothelium independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR. PMID- 26538092 TI - AIP1 is a novel Agenet/Tudor domain protein from Arabidopsis that interacts with regulators of DNA replication, transcription and chromatin remodeling. AB - BACKGROUND: DNA replication and transcription are dynamic processes regulating plant development that are dependent on the chromatin accessibility. Proteins belonging to the Agenet/Tudor domain family are known as histone modification "readers" and classified as chromatin remodeling proteins. Histone modifications and chromatin remodeling have profound effects on gene expression as well as on DNA replication, but how these processes are integrated has not been completely elucidated. It is clear that members of the Agenet/Tudor family are important regulators of development playing roles not well known in plants. METHODS: Bioinformatics and phylogenetic analyses of the Agenet/Tudor Family domain in the plant kingdom were carried out with sequences from available complete genomes databases. 3D structure predictions of Agenet/Tudor domains were calculated by I TASSER server. Protein interactions were tested in two-hybrid, GST pulldown, semi in vivo pulldown and Tandem Affinity Purification assays. Gene function was studied in a T-DNA insertion GABI-line. RESULTS: In the present work we analyzed the family of Agenet/Tudor domain proteins in the plant kingdom and we mapped the organization of this family throughout plant evolution. Furthermore, we characterized a member from Arabidopsis thaliana named AIP1 that harbors Agenet/Tudor and DUF724 domains. AIP1 interacts with ABAP1, a plant regulator of DNA replication licensing and gene transcription, with a plant histone modification "reader" (LHP1) and with non modified histones. AIP1 is expressed in reproductive tissues and its down-regulation delays flower development timing. Also, expression of ABAP1 and LHP1 target genes were repressed in flower buds of plants with reduced levels of AIP1. CONCLUSIONS: AIP1 is a novel Agenet/Tudor domain protein in plants that could act as a link between DNA replication, transcription and chromatin remodeling during flower development. PMID- 26538093 TI - The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep. AB - The objective of this study was to search for polymorphisms in the ovine prion related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT 112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP). PMID- 26538094 TI - Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array. AB - Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies. PMID- 26538095 TI - Art engagement and mental health: experiences of service users of a community based arts programme at Tate Modern, London. AB - OBJECTIVES: To examine the experiences of mental health service users who took part in an arts-based programme at Tate Modern, a major London art gallery. STUDY DESIGN: Exploratory qualitative design. METHODS: Data were collected using in depth semi-structured interviews with 10 mental health service users who had taken part in a community-based programme at Tate Modern. Additionally, six art educators from Tate Modern were interviewed. Concepts that emerged from the text were identified using thematic analysis. RESULTS: All participants valued the gallery-based programme. The three overarching thematic areas were: the symbolic and physical context in which the programme workshops were located; the relational and social context of the programme workshops; and reflections on the relationship between the arts-based programme and subsequent mental health. CONCLUSIONS: Art galleries are increasingly seen to function as vehicles for popular education with mental health service users. This study adds to the growing body of evidence related to how mental health service users experience and reflect on arts-related programmes targeted at them. This study indicates that emphasis on how users experience gallery-based programmes may contribute to a more nuanced understanding of the relationship between art and mental health. PMID- 26538096 TI - Test-retest reliability of the Physical Activity Neighborhood Environment Scale among school students in China. PMID- 26538097 TI - Spectral splitting photovoltaics using perovskite and wideband dye-sensitized solar cells. AB - The extension of the light absorption of photovoltaics into the near-infrared region is important to increase the energy conversion efficiency. Although the progress of the lead halide perovskite solar cells is remarkable, and high conversion efficiency of >20% has been reached, their absorption limit on the long-wavelength side is ~800 nm. To further enhance the conversion efficiency of perovskite-based photovoltaics, a hybridized system with near-infrared photovoltaics is a useful approach. Here we report a panchromatic sensitizer, coded DX3, that exhibits a broad response into the near-infrared, up to ~1100 nm, and a photocurrent density exceeding 30 mA cm(-2) in simulated air mass 1.5 standard solar radiation. Using the DX3-based dye-sensitized solar cell in conjunction with a perovskite cell that harvests visible light, the hybridized mesoscopic photovoltaics achieved a conversion efficiency of 21.5% using a system of spectral splitting. PMID- 26538098 TI - Heritabilities of health traits in Swiss Warmblood horses. AB - REASONS FOR PERFORMING STUDY: There is a lack of evidence regarding genetic parameters of health traits in Swiss Warmblood horses. OBJECTIVES: To estimate heritabilities of equine sarcoid disease, horn quality of hooves, prognathism and increased filling of talocrural joints as a possible indicator for osteochondrosis in Swiss Warmblood horses examined at the field tests for 3-year olds between 2005 and 2013. STUDY DESIGN: Retrospective analysis of breed society database. METHODS: Swiss Warmblood horses were examined clinically by 13 veterinarians at field tests in Switzerland between 2005 and 2013. The presence of sarcoids, horn quality of the hooves, incisor occlusion and increased joint filling were assessed and recorded. Records of 3715 horses were integrated in a pedigree comprising 217,282 horses. Variance components and heritabilities were estimated on the liability scale using multiple-trait Gibbs sampler for animal models (MTGSAM). RESULTS: The prevalences of the examined traits were rather low ranging from 2.4 to 13.0%. Heritabilities estimated were 0.21 +/- 0.07 for the occurrence of sarcoids, 0.04 +/- 0.02 for hooves with markedly brittle and friable horn quality, 0.03 +/- 0.01 for hooves with marked growth ring formation, 0.06 +/- 0.03 for prognathism and 0.08 +/- 0.04 for increased filling of the talocrural joint (an indicator of possible osteochondrosis). The influence of the examiner on the variance of these observations was considerable. CONCLUSIONS: With the exception of equine sarcoid disease, estimates for the heritabilities for the traits examined here were low. A standardised examination protocol may reduce the variance due to the examiner. PMID- 26538099 TI - Population health diagnosis with an ecohealth approach. AB - OBJECTIVE: To analyze the characteristics of health diagnosis according to the ecohealth approach in rural and urban communities in Mexico. METHODS: Health diagnosis were conducted in La Nopalera, from December 2007 to October 2008, and in Atlihuayan, from December 2010 to October 2011. The research was based on three principles of the ecohealth approach: transdisciplinarity, community participation, gender and equity. To collect information, a joint methodology and several techniques were used to stimulate the participation of inhabitants. The diagnostic exercise was carried out in five phases that went from collecting information to prioritization of problems. RESULTS: The constitution of the transdisciplinary team, as well as the participation of the population and the principle of gender/equity were differentials between the communities. In the rural community, the active participation of inhabitants and authorities was achieved and the principles of transdisciplinarity and gender/equity were incorporated. CONCLUSIONS: With all the difficulties that entails the boost in participation, the incorporation of gender/equity and transdisciplinarity in health diagnosis allowed a holistic public health approach closer to the needs of the population. PMID- 26538100 TI - Dentistry and HIV/AIDS related stigma. AB - OBJECTIVE: To analyze HIV/AIDS positive individual's perception and attitudes regarding dental services. METHODS: One hundred and thirty-four subjects (30.0% of women and 70.0% of men) from Nuevo Leon, Mexico, took part in the study (2014). They filled out structured, analytical, self-administered, anonymous questionnaires. Besides the sociodemographic variables, the perception regarding public and private dental services and related professionals was evaluated, as well as the perceived stigma associated with HIV/AIDS, through a Likert-type scale. The statistical evaluation included a factorial and a non-hierarchical cluster analysis. RESULTS: Social inequalities were found regarding the search for public and private dental professionals and services. Most subjects reported omitting their HIV serodiagnosis and agreed that dentists must be trained and qualified to treat patients with HIV/AIDS. The factorial analysis revealed two elements: experiences of stigma and discrimination in dental appointments and feelings of concern regarding the attitudes of professionals or their teams concerning patients' HIV serodiagnosis. The cluster analysis identified three groups: users who have not experienced stigma or discrimination (85.0%); the ones who have not had those experiences, but feel somewhat concerned (12.7%); and the ones who underwent stigma and discrimination and feel concerned (2.3%). CONCLUSIONS: We observed a low percentage of stigma and discrimination in dental appointments; however, most HIV/AIDS patients do not reveal their serodiagnosis to dentists out of fear of being rejected. Such fact implies a workplace hazard to dental professionals, but especially to the very own health of HIV/AIDS patients, as dentists will not be able to provide them a proper clinical and pharmaceutical treatment. PMID- 26538101 TI - Evaluating the use of in-store measures in retail food stores and restaurants in Brazil. AB - OBJECTIVE: To assess inter-rater reliability, test-retest reliability, and construct validity of retail food store, open-air food market, and restaurant observation tools adapted to the Brazilian urban context. METHODS: This study is part of a cross-sectional observation survey conducted in 13 districts across the city of Sao Paulo, Brazil in 2010-2011. Food store and restaurant observational tools were developed based on previously available tools, and then tested it. They included measures on the availability, variety, quality, pricing, and promotion of fruits and vegetables and ultra-processed foods. We used Kappa statistics and intra-class correlation coefficients to assess inter-rater and test-retest reliabilities in samples of 142 restaurants, 97 retail food stores (including open-air food markets), and of 62 restaurants and 45 retail food stores (including open-air food markets), respectively. Construct validity as the tool's abilities to discriminate based on store types and different income contexts were assessed in the entire sample: 305 retail food stores, 8 fruits and vegetable markets, and 472 restaurants. RESULTS: Inter-rater and test-retest reliability were generally high, with most Kappa values greater than 0.70 (range 0.49-1.00). Both tools discriminated between store types and neighborhoods with different median income. Fruits and vegetables were more likely to be found in middle to higher-income neighborhoods, while soda, fruit-flavored drink mixes, cookies, and chips were cheaper and more likely to be found in lower-income neighborhoods. CONCLUSIONS: The measures were reliable and able to reveal significant differences across store types and different contexts. Although some items may require revision, results suggest that the tools may be used to reliably measure the food stores and restaurant food environment in urban settings of middle-income countries. Such studies can help .inform health promotion interventions and policies in these contexts. PMID- 26538102 TI - Lung excision of non-small-cell lung cancer leaves cancer cells in residual lobe: cytological detection using pulmonary vein blood. AB - OBJECTIVES: Lung excision to treat non-small-cell lung cancer (NSCLC) is associated with a worse prognosis when compared with a lobectomy. Cancer relapse may be caused by tumour cells remaining in the residual lobe, the possibility of dislodged cancer cells in the residual lobe is assessed using pulmonary vein blood (PVB) from the resected lung. METHODS: Twenty-eight patients with pathological stage I NSCLC who underwent lung excision followed by a lobectomy were evaluated according to the status of isolated tumour cells (ITCs) (origin of circulating tumour cells) in PVB from the resected lobe. Survival was also assessed according to the status of ITCs. RESULTS: The rate of ITC presence was 60.7% and depended on margin distance/tumour size (M/T) with a threshold of 1.0 30.8% (4/13) in M/T greater than or equal to 1.0 and 86.7% (13/15) in M/T smaller than 1.0 (P = 0.001). PVB-ITC status was no ITCs (N) in 11 (39.3%), only singular cells (S) in 13 (50.0%) and clustered cells (C) in 4 (14.3%). In addition, the survival status of patients with clustered cells was exclusively wrong. CONCLUSION: After pulmonary excision for lung cancer, tumour cells remain in the residual lobe and the morphology of which may indicate recurrence. PMID- 26538103 TI - Minimally invasive Ivor Lewis oesophagogastrectomy in a patient with situs inversus totalis?. AB - Situs inversus totalis (SIT) is a rare congenital condition in which the internal organs of the thoracic and abdominal cavities experience a right-to-left reflection across the sagittal plane. We describe a case of locally advanced adenocarcinoma of the oesophagus treated with minimally invasive oesophagectomy using a laparoscopic and left video-assisted thoracoscopic surgery approach in a patient with situs inversus totalis. PMID- 26538104 TI - Imiquimod 5% as Adjuvant Therapy for Incompletely Excised Infiltrative Nodular Basal Cell Carcinoma and Dermoscopy to Monitor Treatment Response. AB - INTRODUCTION: A relatively novel application for dermoscopy is its use in the monitoring of topical treatment response for non-melanoma skin cancer. Basal cell carcinoma (BCC) is the most frequent type of skin cancer in humans. Surgical excision is still considered the "gold-standard" of treatment. However, a number of topical therapies are now available for the treatment of different types of basal cell carcinoma. CASE REPORT: This case report exemplifies the usefulness of dermoscopy in the monitoring of residual disease after incomplete surgical excision and also in the monitoring of topical treatment response. Imiquimod 5% cream acts as a topical immune response modifier promoting a Th-1 immune response enhancing the removal of neoplastic cells and has proven to reduce deregulated Hedgehog (HH)/GLI signal strength independent of Toll-like receptor signaling, which makes it a valuable adjuvant topical therapy for the treatment of basal cell carcinoma. CONCLUSION: Imiquimod 5% cream is a valuable adjuvant therapy for the treatment of incompletely excised BCC. This case report adds further evidence to the usefulness of dermoscopy in the assessment and monitoring of treatment outcome. PMID- 26538105 TI - Pelvic floor muscle training for erectile dysfunction and climacturia 1 year after nerve sparing radical prostatectomy: a randomized controlled trial. AB - This study aimed to determine whether patients with persistent erectile dysfunction (ED), minimum 12 months after radical prostatectomy (RP), experienced a better recovery of erectile function (EF) with pelvic floor muscle training (PFMT) compared with patients without this intervention. Second, we aimed to investigate the effect of PFMT on climacturia. All patients, who underwent RP, with persistent ED of minimum 1 year post operation were eligible. The treatment group started PFMT immediately at 12 months post operation and the control group started at 15 months after RP. All patients received PFMT during 3 months. The sample size needed to detect with 80% power a 6 points-difference regarding the EF-domain of the International Index of Erectile Function (IIEF), was at least 12 subjects per group. Patients were evaluated using the IIEF and questioned regarding climacturia. Differences between groups at 15 months were evaluated with Mann-Whitney U-test and Fisher's exact test. As a result, the treatment group had a significantly better EF than the control group at 15 months after surgery (P=0.025). Other subdomains of the IIEF remained constant for both groups. The effect of PFMT was maintained during follow-up. At 15 months, a significantly higher percentage of patients in the treatment group showed an improvement regarding climacturia (P=0.004). PMID- 26538106 TI - Inferring plant microRNA functional similarity using a weighted protein-protein interaction network. AB - BACKGROUND: MiRNAs play a critical role in the response of plants to abiotic and biotic stress. However, the functions of most plant miRNAs remain unknown. Inferring these functions from miRNA functional similarity would thus be useful. This study proposes a new method, called PPImiRFS, for inferring miRNA functional similarity. RESULTS: The functional similarity of miRNAs was inferred from the functional similarity of their target gene sets. A protein-protein interaction network with semantic similarity weights of edges generated using Gene Ontology terms was constructed to infer the functional similarity between two target genes that belong to two different miRNAs, and the score for functional similarity was calculated using the weighted shortest path for the two target genes through the whole network. The experimental results showed that the proposed method was more effective and reliable than previous methods (miRFunSim and GOSemSim) applied to Arabidopsis thaliana. Additionally, miRNAs responding to the same type of stress had higher functional similarity than miRNAs responding to different types of stress. CONCLUSIONS: For the first time, a protein-protein interaction network with semantic similarity weights generated using Gene Ontology terms was employed to calculate the functional similarity of plant miRNAs. A novel method based on calculating the weighted shortest path between two target genes was introduced. PMID- 26538107 TI - Feelings of worthlessness during a single complicated major depressive episode predict postremission suicide attempt. AB - OBJECTIVE: To establish which symptoms of major depressive episode (MDE) predict postremission suicide attempts in complicated single-episode cases. METHOD: Using the nationally representative two-wave National Epidemiologic Survey on Alcohol and Related Conditions data set, we identified wave 1 lifetime single-episode MDE cases in which the episode remitted by the beginning of the wave 2 three-year follow-up period (N = 2791). The analytic sample was further limited to 'complicated' cases (N = 1872) known to have elevated suicide attempt rates, defined as having two or more of the following: suicidal ideation, marked role impairment, feeling worthless, psychomotor retardation, and prolonged (>6 months) duration. RESULTS: Logistic regression analyses showed that, after controlling for wave 1 suicide attempt which significantly predicted postremission suicide attempt (OR = 10.0), the additional complicated symptom 'feelings of worthlessness' during the wave 1 index episode significantly and very substantially predicted postremission suicide attempt (OR = 6.96). Neither wave 1 psychomotor retardation nor wave 1 suicidal ideation nor any of the other wave 1 depressive symptoms were significant predictors of wave 2 suicide attempt. CONCLUSION: Among depressive symptoms during an MDE, feelings of worthlessness is the only significant indicator of elevated risk of suicide attempt after the episode has remitted, beyond previous suicide attempts. PMID- 26538108 TI - Catalytic Depolymerization of Chitin with Retention of N-Acetyl Group. AB - Chitin, a polymer of N-acetylglucosamine units with beta-1,4-glycosidic linkages, is the most abundant marine biomass. Chitin monomers containing N-acetyl groups are useful precursors to various fine chemicals and medicines. However, the selective conversion of robust chitin to N-acetylated monomers currently requires a large excess of acid or a long reaction time, which limits its application. We demonstrate a fast catalytic transformation of chitin to monomers with retention of N-acetyl groups by combining mechanochemistry and homogeneous catalysis. Mechanical-force-assisted depolymerization of chitin with a catalytic amount of H2SO4 gave soluble short-chain oligomers. Subsequent hydrolysis of the ball milled sample provided N-acetylglucosamine in 53% yield, and methanolysis afforded 1-O-methyl-N-acetylglucosamine in yields of up to 70%. Our process can greatly reduce the use of acid compared to the conventional process. PMID- 26538109 TI - An exploratory pilot study to assess self-perceived changes among social assistance recipients regarding employment prospects after receiving dental treatment. AB - BACKGROUND: Strengthening self-efficacy in job-seeking among individuals with dental problems has been identified as an important factor in facilitating job procurement and maintenance. There is no knowledge about whether receiving dental treatment improves someone's self-efficacy in seeking a job. This work explores this relationship. METHODS: An exploratory pilot study of a convenience sample of 30 social assistance recipients of Ontario, Canada, was conducted using a pre- and post-dental treatment survey, which included both quantitative and qualitative components. The survey included two validated instruments Oral Health Impact Profile (OHIP-14) and Job-Seeking Self-efficacy scale (JSS). Changes in scores of both scales following dental treatment were calculated. Pearson correlation was performed between OHIP-14 and JSS scores. Qualitative data were transcribed and interrelated ideas were grouped together to generate themes. RESULTS: Mean scores for OHIP-14 (23.4 to 6.7, p < 0.001, effect size: 1.75) and median scores for JSS (4.9 to 5.5, p = 0.002, effect size: 0.40) changed significantly after receiving dental treatment. A significant negative correlation (-0.56, p = 0.001) was observed between OHIP-14 and JSS scores indicating that job-seeking self-efficacy improves with improvement in oral health related quality of life (OHRQoL). Qualitative analysis reveals participants' physical and psychosocial impacts of dental problems; barriers experienced in accessing dental care and seeking a job; and changes perceived after receiving dental care. CONCLUSION: Results of our survey indicate that social assistance recipients experience negative impacts of dental problems and perceive improvements in OHRQoL and job-seeking self-efficacy after receiving dental treatment. PMID- 26538110 TI - Direct printing of patterned three-dimensional ultrafine fibrous scaffolds by stable jet electrospinning for cellular ingrowth. AB - Electrospinning has been widely used to produce ultrafine fibers in microscale and nanoscale; however, traditional electrospinning processes are currently beset by troublesome limitations in fabrication of 3D periodic porous structures because of the chaotic nature of the electrospinning jet. Here we report a novel strategy to print 3D poly(L-lactic acid) (PLLA) ultrafine fibrous scaffolds with the fiber diameter of approximately 2 MUm by combining a stable jet electrospinning method and an X-Y stage technique. Our approach allows linearly deposited electrospun ultrafine fibers to assemble into 3D structures with tunable pore sizes and desired patterns. Process conditions (e.g., plotting speed, feeding rate, and collecting distance) were investigated in order to achieve stable jet printing of ultrafine PLLA fibers. The proposed 3D scaffold was successfully used for cell penetration and growth, demonstrating great potential for tissue engineering applications. PMID- 26538112 TI - Fossils of parasites: what can the fossil record tell us about the evolution of parasitism? AB - Parasites are common in many ecosystems, yet because of their nature, they do not fossilise readily and are very rare in the geological record. This makes it challenging to study the evolutionary transition that led to the evolution of parasitism in different taxa. Most studies on the evolution of parasites are based on phylogenies of extant species that were constructed based on morphological and molecular data, but they give us an incomplete picture and offer little information on many important details of parasite-host interactions. The lack of fossil parasites also means we know very little about the roles that parasites played in ecosystems of the past even though it is known that parasites have significant influences on many ecosystems. The goal of this review is to bring attention to known fossils of parasites and parasitism, and provide a conceptual framework for how research on fossil parasites can develop in the future. Despite their rarity, there are some fossil parasites which have been described from different geological eras. These fossils include the free-living stage of parasites, parasites which became fossilised with their hosts, parasite eggs and propagules in coprolites, and traces of pathology inflicted by parasites on the host's body. Judging from the fossil record, while there were some parasite-host relationships which no longer exist in the present day, many parasite taxa which are known from the fossil record seem to have remained relatively unchanged in their general morphology and their patterns of host association over tens or even hundreds of millions of years. It also appears that major evolutionary and ecological transitions throughout the history of life on Earth coincided with the appearance of certain parasite taxa, as the appearance of new host groups also provided new niches for potential parasites. As such, fossil parasites can provide additional data regarding the ecology of their extinct hosts, since many parasites have specific life cycles and transmission modes which reflect certain aspects of the host's ecology. The study of fossil parasites can be conducted using existing techniques in palaeontology and palaeoecology, and microscopic examination of potential material such as coprolites may uncover more fossil evidence of parasitism. However, I also urge caution when interpreting fossils as examples of parasites or parasitism-induced traces. I point out a number of cases where parasitism has been spuriously attributed to some fossil specimens which, upon re-examination, display traits which are just as (if not more) likely to be found in free-living taxa. The study of parasite fossils can provide a more complete picture of the ecosystems and evolution of life throughout Earth's history. PMID- 26538111 TI - 2D cine DENSE with low encoding frequencies accurately quantifies cardiac mechanics with improved image characteristics. AB - BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (ke) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a ke of 0.10 cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high ke. Additionally, the high sensitivity comes with the costs of increased phase wrapping and intra-voxel dephasing. We hypothesized that ke below 0.10 cycles/mm can be used to improve image characteristics and provide accurate measures of cardiac mechanics. METHODS: Spiral cine DENSE images were obtained for 10 healthy subjects and 10 patients with a history of heart disease on a 3 T Siemens Trio. A mid-ventricular short-axis image was acquired with different ke: 0.02, 0.04, 0.06, 0.08, and 0.10 cycles/mm. Peak twist, circumferential strain, and radial strain were compared between acquisitions employing different ke using Bland-Altman analyses and coefficients of variation. The percentage of wrapped pixels in the phase images at end-systole was calculated for each ke. The dephasing of the blood signal and signal to noise ratio (SNR) were also calculated and compared. RESULTS: Negligible differences were seen in strains and twist for all ke between 0.04 and 0.10 cycles/mm. These differences were of the same magnitude as inter-test differences. Specifically, the acquisitions with 0.04 cycles/mm accurately quantified cardiac mechanics and had zero phase wrapping. Compared to 0.10 cycles/mm, the acquisitions with 0.04 cycles/mm had 9 % greater SNR and negligible differences in blood pool dephasing. CONCLUSIONS: For 2D cine DENSE with through-plane dephasing, the encoding frequency can be lowered to 0.04 cycles/mm without compromising the quantification of twist or strain. The amount of wrapping can be reduced with this lower value to greatly simplify the input to unwrapping algorithms. The strain and twist results from studies using different encoding frequencies can be directly compared. PMID- 26538114 TI - The electrochemical oxidation of toluene catalysed by Co(II) in N-butyl-N methylpyrrolidinium bis(trifluoromethylsulfonyl)imide. AB - The electrochemical oxidation of toluene in N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([bmpyr](+)[Ntf2](-)) was investigated by using cyclic voltammetry and galvanostatic electrolysis in the presence of Co(II) at a Pt disc working electrode. Cyclic voltammetry (CV) investigations revealed that Co(II)-Co(III) oxidation is a diffusion controlled electron transfer process. The diffusion coefficient values of Co(II) were found to increase from 0.38 * 10(-7) to 1.9 * 10(-7) cm(2) s(-1) as the temperature was increased from 25 degrees C to 80 degrees C. The CV peak current for toluene electro-oxidation increased by nearly 7 fold in the presence of Co(II) demonstrating a good catalytic effect. Co(II) catalysed galvanostatic electrolysis of toluene at room temperature has shown that benzaldehyde was formed along with a small quantity of 3-methyl-1 hexanol. PMID- 26538115 TI - High prevalence of contact allergy in adolescence: results from the population based BAMSE birth cohort. AB - BACKGROUND: Contact allergy is common among adults. However, little is known about the prevalence in adolescents. OBJECTIVES: To assess the prevalence of allergy to common contact allergens in Swedish adolescents in the general population. PARTICIPANTS AND METHODS: The BAMSE cohort is a population-based birth cohort with the main aim of studying the risk factors for asthma, rhinitis, and atopic dermatitis. Patch testing was performed at the 16-year follow-up. The test (TRUE Test((r)) ) was applied at home, and removed 2 days later by nurses, who recorded and photographed the results. Dermatologists made final assessments on the basis of photographs and protocols. RESULTS: Two thousand two hundred and eighty-five participants (88% of all 16-year follow-up participants) were patch tested; 15.3% had at least one positive reaction. Contact allergy was more common in girls than in boys (17.0% versus 13.4%, p = 0.018). Sensitization to nickel was most common (7.5%), followed by sensitization to fragrance mix I (2.1%) and p tert-butylphenol formaldehyde resin (1.9%). Nickel allergy was more frequent in girls (9.8% versus 4.9%, p < 0.001). Solitary sensitization to cobalt was more common than co-sensitization to nickel and cobalt. CONCLUSIONS: The prevalence of contact allergy in adolescents is of almost the same high magnitude as in adults. The applied method was feasible in the population-based setting. PMID- 26538116 TI - Diastereoselective Strategies towards Thia[n]helicenes. AB - In the present study, we have investigated different strategies for diastereoselective synthesis of thia[n]helicenes. We describe the introduction of different chiral auxiliaries at various positions and investigated their effect in the photocyclization reaction. Different chiral groups were placed at the sterically hindered position of the helical core and their interactions with various solvents and metals like copper were investigated. The use of Cu(I) salts has led to high diastereoselectivity in the photocyclization process and we were successful in obtaining the thia[5]helicene in enantiomerically pure form in good yield. The single diastereomer obtained was characterized by X-ray crystallography. From the study of the barrier of racemization of these thia[5]helicenes, the stability was found to be comparable to unsubstituted tetrathia[7]helicenes and substituted diazadithia[7]helicenes. This approach provides an easy access to enantiopure helicenes. PMID- 26538117 TI - Linc00152 promotes proliferation in gastric cancer through the EGFR-dependent pathway. AB - BACKGROUND: Linc00152 has been identified highly associated with the tumorigenesis and development of gastric cancer, however, the detailed mechanism of Linc00152 involved still remains unclear. METHODS: RT-PCR and western blot were used to detect the expression of Linc00152 and EGFR. The CCK8 and EDU assay was employed to measure cell proliferation while xenotransplantation technology was applied in BALB/C nude mice. The interaction between lncRNA and target protein was investigated by RNA pull-down and RNA immunoprecipitation assay. RESULTS: In this study, we first confirmed the upregulation of cytoplasmic expressed Linc00152 in 72 pair tissues of gastric patients. A suppression of cell proliferation and tumor growth was obtained in MGC803 and HGC-27 cells treated with Linc00152 shRNA. RNA pull-down and RIP assay revealed that Linc00152 could directly bind with EGFR which caused an activation of PI3K/AKT signaling. CONCLUSION: We first found that Linc00152 could promote tumor growth through EGFR mediated PI3K/AKT pathway which may serve as potential targets for therapy in the future. PMID- 26538118 TI - Parallel Accumulation-Serial Fragmentation (PASEF): Multiplying Sequencing Speed and Sensitivity by Synchronized Scans in a Trapped Ion Mobility Device. AB - In liquid chromatography-mass spectrometry (LC-MS)-based proteomics, many precursors elute from the column simultaneously. In data-dependent analyses, these precursors are fragmented one at a time, whereas the others are discarded entirely. Here we employ trapped ion mobility spectrometry (TIMS) on an orthogonal quadrupole time-of-flight (QTOF) mass spectrometer to remove this limitation. In TIMS, all precursor ions are accumulated in parallel and released sequentially as a function of their ion mobility. Instead of selecting a single precursor mass with the quadrupole mass filter, we here implement synchronized scans in which the quadrupole is mass positioned with sub-millisecond switching times at the m/z values of appropriate precursors, such as those derived from a topN precursor list. We demonstrate serial selection and fragmentation of multiple precursors in single 50 ms TIMS scans. Parallel accumulation-serial fragmentation (PASEF) enables hundreds of MS/MS events per second at full sensitivity. Modeling the effect of such synchronized scans for shotgun proteomics, we estimate that about a 10-fold gain in sequencing speed should be achievable by PASEF without a decrease in sensitivity. PMID- 26538119 TI - Rough-set-based ADR signaling from spontaneous reporting data with missing values. AB - Spontaneous reporting systems of adverse drug events have been widely established in many countries to collect as could as possible all adverse drug events to facilitate the detection of suspected ADR signals via some statistical or data mining methods. Unfortunately, due to privacy concern or other reasons, the reporters sometimes may omit consciously some attributes, causing many missing values existing in the reporting database. Most of research work on ADR detection or methods applied in practice simply adopted listwise deletion to eliminate all data with missing values. Very little work has noticed the possibility and examined the effect of including the missing data in the process of ADR detection. This paper represents our endeavor towards the exploration of this question. We aim at inspecting the feasibility of applying rough set theory to the ADR detection problem. Based on the concept of utilizing characteristic set based approximation to measure the strength of ADR signals, we propose twelve different rough set based measuring methods and show only six of them are feasible for the purpose. Experimental results conducted on the FARES database show that our rough-set-based approach exhibits similar capability in timeline warning of suspicious ADR signals as traditional method with missing deletion, and sometimes can yield noteworthy measures earlier than the traditional method. PMID- 26538120 TI - Aerobic Fitness and Inhibition in Young Children: Moderating Roles of ADHD Status and Age. AB - We examined the relation between aerobic fitness and inhibition in young children with and without attention deficit hyperactivity disorder (ADHD)-risk status. Participants (91 ADHD risk, 107 typically developing, Mage = 6.83, 53.5% male, 68.2% Caucasian) completed an assessment of aerobic fitness and a flanker task requiring variable amounts of inhibitory control. Aerobic fitness was positively associated with inhibition. When inhibitory control demands were largest, the relation varied as a function of ADHD-risk status such that the link between aerobic fitness and inhibition was significant only for children with ADHD risk. The relation between aerobic fitness, status, and inhibition was further moderated by age for interference control. Specifically, the positive relation between aerobic fitness and interference control was only significant for younger children with ADHD risk. A fitness-cognition link appears in young childhood that seems particularly salient for those in the earliest school years with ADHD risk. The findings extend work on typically developing children and suggest that exploring aerobic fitness interventions to address executive function impairments in children at risk for ADHD is warranted. PMID- 26538121 TI - The Effects of SELEX Conditions on the Resultant Aptamer Pools in the Selection of Aptamers Binding to Bacterial Cells. AB - Aptamers of high affinity and specificity have a wide range of analytic and clinical applications. Selection of DNA or RNA aptamer molecules usually involves systematic evolution of ligands via exponential enrichment (SELEX), in which a random DNA or RNA library is incubated with a target molecule, and the oligonucleotides that bind the target are then separated from the nonbinders, PCR amplified, and used as refined libraries in the next round of selection. Conventional SELEX methodologies require the use of purified target molecules and their immobilization onto a solid support. However, purified targets from cells are not always available, and fixing the target to a support may alter its conformation. To overcome these problems, we have developed a SELEX technique using live bacterial cells in suspension as targets, for selecting DNA aptamers specific to cell-surface molecules. Through the selection of aptamers binding to Lactobacillus acidophilus and Streptococcus pyogenes, we report here optimization of this technique and show how varying selection conditions impact the characteristics of resultant aptamer pools, including the binding affinity, selectivity, and the secondary structures. We found that the use of larger starting library sequence diversity, gel purification of the subsequent pools, and the introduction of counter-selection resulted in a more efficient SELEX process and more selective aptamers. A SELEX protocol with lower starting sequence diversity, the use of heat denaturation, and the absence of counter selection still resulted in high-affinity aptamer sequences specific to the target cell types; however, the SELEX process was inefficient, requiring 20 rounds, and the aptamers were not specific to the strain of the bacterial cells. Strikingly, two different SELEX methodologies yielded the same sequence that bound strongly to the target S. pyogenes cells, suggesting the robustness of the bacterial cell-SELEX technique. PMID- 26538123 TI - Long-Range Effects of Na(+) Binding in Na,K-ATPase Reported by ATP. AB - This paper addresses the question of long-range interactions between the intramembranous cation binding sites and the cytoplasmic nucleotide binding site of the ubiquitous ion-transporting Na,K-ATPase using (13)C cross-polarization magic-angle spinning (CP-MAS) solid-state nuclear magnetic resonance. High affinity ATP binding is induced by the presence of Na(+) as well as of Na-like substances such as Tris(+), and these ions are equally efficient promoters of nucleotide binding. CP-MAS analysis of bound ATP with Na,K-ATPase purified from pig kidney membranes reveals subtle differences in the nucleotide interactions within the nucleotide site depending on whether Na(+) or Tris(+) is used to induce binding. Differences in chemical shifts for ATP atoms C1' and C5' observed in the presence of Na(+) or Tris(+) suggest alterations in the residues surrounding the bound nucleotide, hydrogen bonding, and/or conformation of the ribose ring. This is taken as evidence of a long-distance communication between the Na(+)-filled ion sites in the membrane interior and the nucleotide binding site in the cytoplasmic domain and reflects the first conformational change ultimately leading to phosphorylation of the enzyme. Stopped-flow fluorescence measurements with the nucleotide analogue eosin show that the dissociation rate constant for eosin is larger in Tris(+) than in Na(+), giving kinetic evidence of the difference in structural effects of Na(+) and Tris(+). According to the recent crystal structure of the E1.AlF4(-).ADP.3Na(+) form, the coupling between the ion binding sites and the nucleotide side is mediated by, among others, the M5 helix. PMID- 26538122 TI - The Code of Silence: Widespread Associations Between Synonymous Codon Biases and Gene Function. AB - Some mutations in gene coding regions exchange one synonymous codon for another, and thus do not alter the amino acid sequence of the encoded protein. Even though they are often called 'silent,' these mutations may exhibit a plethora of effects on the living cell. Therefore, they are often selected during evolution, causing synonymous codon usage biases in genomes. Comparative analyses of bacterial, archaeal, fungal, and human cancer genomes have found many links between a gene's biological role and the accrual of synonymous mutations during evolution. In particular, highly expressed genes in certain functional categories are enriched with optimal codons, which are decoded by the abundant tRNAs, thus enhancing the speed and accuracy of the translating ribosome. The set of genes exhibiting codon adaptation differs between genomes, and these differences show robust associations to organismal phenotypes. In addition to selection for translation efficiency, other distinct codon bias patterns have been found in: amino acid starvation genes, cyclically expressed genes, tissue-specific genes in animals and plants, oxidative stress response genes, cellular differentiation genes, and oncogenes. In addition, genomes of organisms harboring tRNA modifications exhibit particular codon preferences. The evolutionary trace of codon bias patterns across orthologous genes may be examined to learn about a gene's relevance to various phenotypes, or, more generally, its function in the cell. PMID- 26538124 TI - Erratum to: Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations? PMID- 26538125 TI - Reduction of a Whole-Body Physiologically Based Pharmacokinetic Model to Stabilise the Bayesian Analysis of Clinical Data. AB - Whole-body physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development for their ability to predict drug concentrations in clinically relevant tissues and to extrapolate across species, experimental conditions and sub-populations. A whole-body PBPK model can be fitted to clinical data using a Bayesian population approach. However, the analysis might be time consuming and numerically unstable if prior information on the model parameters is too vague given the complexity of the system. We suggest an approach where (i) a whole-body PBPK model is formally reduced using a Bayesian proper lumping method to retain the mechanistic interpretation of the system and account for parameter uncertainty, (ii) the simplified model is fitted to clinical data using Markov Chain Monte Carlo techniques and (iii) the optimised reduced PBPK model is used for extrapolation. A previously developed 16-compartment whole-body PBPK model for mavoglurant was reduced to 7 compartments while preserving plasma concentration-time profiles (median and variance) and giving emphasis to the brain (target site) and the liver (elimination site). The reduced model was numerically more stable than the whole-body model for the Bayesian analysis of mavoglurant pharmacokinetic data in healthy adult volunteers. Finally, the reduced yet mechanistic model could easily be scaled from adults to children and predict mavoglurant pharmacokinetics in children aged from 3 to 11 years with similar performance compared with the whole-body model. This study is a first example of the practicality of formal reduction of complex mechanistic models for Bayesian inference in drug development. PMID- 26538126 TI - 'Vulval oedema': a conundrum! AB - Massive oedema of the vulva appears to be a sequel of an underlying systemic disease in pregnant women. Isolated vulval oedema in pregnancy is rare. Vulval oedema has been treated, depending on pathophysiology, with steroids, furosemide, albumin and continuous epidural analgaesia. We present a case of vulval oedema, where the oedema was confined to the labia minora in a healthy young pregnant woman. The patient was in pain and extreme discomfort due to the labial swelling, and caesarean section was being considered for delivery as the massive oedema would obstruct the birth canal. The swelling, however, resolved successfully by simple drainage. In the literature, there have been cases delivered by caesarean section as vulval swelling was causing an obstruction. PMID- 26538127 TI - Early recognition is the key to success: pulseless electrical activity (PEA) as a manifestation of heparin-induced anaphylactoid reaction. AB - A 64-year-old man underwent mitral valve replacement. He was hospitalised 9 days later because of slurring of speech and left-sided facial weakness. During hospitalisation, unfractionated heparin (UFH) bolus and drip were initiated due to subtherapeutic international normalised ratio. Within 5 min of UFH bolus, the patient began to experience symptoms of dyspnoea, followed by pulseless electrical activity arrest. He was successfully resuscitated. A decline in platelet count >50% was noted immediately after UFH bolus and cardiac arrest. A diagnosis of heparin-induced thrombocytopenia and anaphylactoid reaction was considered (4Ts score of 7). Heparin was discontinued and argatroban was started. A platelet factor 4 (PF4) assay was strongly positive. Platelet counts subsequently improved following discontinuation of heparin. PMID- 26538128 TI - Stranded under the Prom: impacted gravid uterus presenting as acute urinary retention. AB - Acute urinary retention in pregnancy secondary to an impacted uterus is a rare occurrence. It can have non-specific presentations, leading to delay in diagnosis, hence potentially increasing maternal and fetal morbidity and mortality. A number of risk factors for the condition have been identified. We describe the case of a 31-year-old woman presenting with urinary retention at 18 weeks' gestation. Clinical examination revealed features consistent with a gravid uterus impacted in the pelvis. Management with urinary catheterisation followed by gentle manual disimpaction of the uterus was successful. PMID- 26538129 TI - Automated implantable cardioverter defibrillator lead infection in a patient with previous superior vena cava thrombosis. AB - We present a case of a 44-year-old woman who presented with cough, pleuritic chest pain and fever leading to a diagnosis of pneumonia+/-pulmonary embolism. She had a history of familial hypertrophic obstructive cardiomyopathy (HOCM), for which an automated implantable cardioverter defibrillator (AICD) had been implanted, and a subsequent superior vena cava (SVC) thrombus, for which she was anticoagulated with warfarin. On admission, blood cultures grew a coagulase negative Staphylococcus. CT pulmonary angiogram and transoesophageal echocardiography (TOE) were performed and revealed large vegetations adherent to the AICD leads with complete occlusion of the SVC. The infected leads were the source of sepsis. Open surgery was planned. For cardiopulmonary bypass, the venous cannula was inserted in the inferior vena cava (IVC) and a completely bloodless field was obtained in the right atrium allowing for the extraction of the AICD leads completely, along with the adherent vegetations from within. PMID- 26538130 TI - Fatal fungal nephropathy in an immunocompetent host: an interesting case. PMID- 26538131 TI - Fibrosing mediastinitis: a rare complication of histoplasmosis. AB - We report a case of a 29-year-old man who presented with intermittent haemoptysis for about 18 months. Previously, his symptoms had been diagnosed as musculoskeletal pain and later as pneumonia. CT found a venous infarct in the right lung in addition to extensive lymphadenopathy in the mediastinum and pulmonary hila, with associated calcifications almost completely occluding the superior vena cava and azygos vein. Further questioning revealed that the patient had once worked on an organic farm in Colorado. Subsequent work up was positive for histoplasmosis yeast antibodies. The patient was diagnosed with fibrosing mediastinitis (FM) and started on itraconazole for 3 months. We note that FM is a rare complication of histoplasmosis and can present as chronic haemoptysis. Travel history is an important aspect of the clinical evaluation. Antifungal agents have shown some efficacy in treating histoplasmosis-related FM. PMID- 26538133 TI - Computational Approach to Explore the B/A Junction Free Energy in DNA. AB - Protein-DNA interactions induce conformational changes in DNA such as B- to A form transitions at a local level. Such transitions are associated with a junction free energy cost at the boundary of two different conformations in a DNA molecule. In this study, we performed umbrella sampling simulations to find the free energy values of the B-A transition at the dinucleotide and trinucleotide level of DNA. Using a combination of dinucleotide and trinucleotide free energy costs obtained from simulations, we calculated the B/A junction free energy. Our study shows that the B/A junction free energy is 0.52 kcal mol(-1) for the A philic GG step and 1.59 kcal mol(-1) for the B-philic AA step. This observation is in agreement with experimentally derived values. After excluding junction effects, we obtained an absolute free energy cost for the B- to A-form conversion for all the dinucleotide steps. These absolute free energies may be used for predicting the propensity of structural transitions in DNA. PMID- 26538132 TI - Genetic variations in STAT4,C2,HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis. AB - Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV) related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P = 1.79 * 10(-2), OR = 1.17, 95% CI = 1.03-1.34; rs9267673: P = 4.91 * 10(-4), OR = 1.37, 95% CI = 1.15-1.63; rs2647073: P = 3.53 * 10(-5), OR = 1.63, 95% CI = 1.29-2.06; rs3997872: P = 4.22 * 10(-4), OR = 1.86, 95% CI = 1.32-2.62; rs9275319: P = 1.30 * 10(-2), OR = 1.32, 95% CI = 1.06-1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC. PMID- 26538134 TI - [Controlling in outpatient radiology]. AB - Radiology is among the medical disciplines which require the highest investment costs in the healthcare system. The need to design efficient workflows to ensure maximum utilization of the equipment has long been known. In order to be able to establish a sound financial plan prior to a project or equipment purchase, the costs of an examination have to be broken down by modality and compared with the reimbursement rates. Obviously, the same holds true for operative decisions when scarce human resources have to be allocated. It is the task of controlling to review the economic viability of the different modalities and ideally, the results are incorporated into the management decision-making processes. The main section of this article looks at the recognition and allocation of direct and indirect costs in a medical center (Medizinisches Versorgungszentrum - MVZ) in the German North Rhine region. The profit contribution of each examination is determined by deducting the costs from the income generated by the treatment of patients with either private or statutory health insurance. PMID- 26538135 TI - [Evaluation in medical residency training programs]. AB - BACKGROUND: For resident doctors the acquisition of technical and professional competence is decisive for the successful practice of their activities. Competency and professional development of resident doctors benefit from regular self-reflection and assessment by peers. While often promoted and recommended by national educational authorities, the implementation of a robust evaluation process in the clinical routine is often counteracted by several factors. OBJECTIVE: The aim of the study was to test a self-developed digital evaluation system for the assessment of radiology residents at our institute for practicality and impact with regard to the radiological training. MATERIAL AND METHODS: The intranet-based evaluation system was implemented in January 2014, which allowed all Radiology consultants to submit a structured assessment of the Radiology residents according to standardized criteria. It included 7 areas of competency and 31 questions, as well as a self-assessment module, both of which were filled out electronically on a 3-month basis using a 10-point scale and the opportunity to make free text comments. The results of the mandatory self evaluation by the residents were displayed beside the evaluation by the supervisor. Access to results was restricted and quarterly discussions with the residents were conducted confidentially and individually. RESULTS AND DISCUSSION: The system was considered to be practical to use and stable in its functionality. The centrally conducted anonymous national survey of residents revealed a noticeable improvement of satisfaction with the institute assessment for the criterion "regular feedback"compared to the national average. Since its implementation the system has been further developed and extended and is now available for other institutions. PMID- 26538136 TI - [Local imaging of rectal cancer--update 2015: MRI as imaging biomarker]. AB - The significance of state of the art magnetic resonance imaging (MRI) for rectal cancer goes far beyond the detection and diagnostics of local dispersion and is increasingly focusing on patient prognosis. The identification of prognostic factors, such as tumor (T) and nodal (N) status, involvement of the circumferential resection margin, presence of extramural vascular invasion, tumor response prediction following neoadjuvant therapy, therapy-related changes in microcirculation, permeability and tissue cellularity and structured reporting are important elements of advanced rectal cancer imaging. In this context, multiparametric MRI is progressively evolving into a powerful imaging biomarker. PMID- 26538137 TI - Epidemiology of hepatitis C virus infection in a large Israeli health maintenance organization. AB - Hepatitis C affects an estimated 130 million people worldwide and is a major cause of chronic liver disease. This retrospective database study aims to describe the epidemiology of HCV-infected patients in Maccabi Healthcare Services, a 2-million-member health maintenance organization in Israel. HCV was identified by cross-linking diagnoses, laboratory data, and dispensed HCV treatment (1993-2013). The point-prevalence of HCV in 2012 and annual incidence of newly-diagnosed HCV during 2003-2012 (index period) were calculated. The age adjusted prevalence of HCV was 5.19/1,000 population (n = 10,648). The highest prevalence was found among males and in patients aged 35-54 years. Two thirds of HCV-infected patients were immigrants from the former Soviet Union (FSU). HCV genotype 1 was predominant (67%). A total of 6,150 patients were newly diagnosed with HCV infection during the index period. The age-standardized rate of newly diagnosed HCV declined from over 50/100,000 (2003) to 15/100,000 (2012). This rate was highest in males from the FSU, particularly for birth cohorts in 1950 70. The study results suggest that the reported incidence of HCV infection in Israel is declining, while prevalence is particularly high among FSU immigrants and genotype 1 is predominant. As the HCV treatment landscape evolves, these estimates can inform future studies and health technology assessments. PMID- 26538138 TI - Development and Validation of the Morphing Fear Questionnaire (MFQ). AB - : Morphing fears (also called transformation obsessions) involve concerns that a person may become contaminated by and acquire undesirable characteristics of others. These symptoms are found in patients with obsessive-compulsive disorder (OCD) and are thought to be related to mental contamination. Given the high levels of distress and interference morphing fears can cause, a reliable and valid assessment measure is needed. This article describes the development and evaluation of the Morphing Fear Questionnaire (MFQ), a 13-item measure designed to assess for the presence and severity of morphing fears. A sample of 900 participants took part in the research. Of these, 140 reported having a current diagnosis of OCD (SR-OCD) and 760 reported never having had OCD (N-OCD; of whom 24 reported a diagnosis of an anxiety disorder and 23 reported a diagnosis of depression). Factor structure, reliability and construct and criterion-related validity were investigated. Exploratory and confirmatory factor analyses supported a one-factor structure replicable across the N-OCD and SR-OCD group. The MFQ was found to have high internal consistency and good temporal stability and showed significantly greater associations with convergent measures (assessing obsessive-compulsive symptoms, mental contamination, thought-action fusion and magical thinking) than with divergent measures (assessing depression and anxiety). Moreover, the MFQ successfully discriminated between the SR-OCD sample and the N-OCD group, anxiety disorder sample and depression sample. These findings suggest that the MFQ has sound psychometric properties and that it can be used to assess morphing fear. Clinical implications are discussed. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Little remains known about morphing fears, but it is an important area of investigation due to symptoms being highly distressing and often debilitating Because morphing fears commonly present as obscure symptoms, they may not be recognized as a type of OCD The MFQ is a robust measure with clinical utility; it can facilitate recognition and assessment of morphing fears The MFQ will allow for further investigations of the prevalence, correlates and treatment outcomes of morphing fears. PMID- 26538139 TI - Some thoughts about recurrent Takotsubo syndrome attacks in a child with seizures. PMID- 26538140 TI - Five minutes with...Joanna Rose. PMID- 26538141 TI - A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway. AB - Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid's components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance. PMID- 26538142 TI - Evolution of SUMO Function and Chain Formation in Insects. AB - SUMOylation, the covalent binding of Small Ubiquitin-like Modifier (SUMO) to target proteins, is a posttranslational modification that regulates critical cellular processes in eukaryotes. In insects, SUMOylation has been studied in holometabolous species, particularly in the dipteran Drosophila melanogaster, which contains a single SUMO gene (smt3). This has led to the assumption that insects contain a single SUMO gene. However, the analysis of insect genomes shows that basal insects contain two SUMO genes, orthologous to vertebrate SUMO1 and SUMO2/3. Our phylogenetical analysis reveals that the SUMO gene has been duplicated giving rise to SUMO1 and SUMO2/3 families early in Metazoan evolution, and that later in insect evolution the SUMO1 gene has been lost after the Hymenoptera divergence. To explore the consequences of this loss, we have examined the characteristics and different biological functions of the two SUMO genes (SUMO1 and SUMO3) in the hemimetabolous cockroach Blattella germanica and compared them with those of Drosophila Smt3. Here, we show that the metamorphic role of the SUMO genes is evolutionary conserved in insects, although there has been a regulatory switch from SUMO1 in basal insects to SUMO3 in more derived ones. We also show that, unlike vertebrates, insect SUMO3 proteins cannot form polySUMO chains due to the loss of critical lysine residues within the N-terminal part of the protein. Furthermore, the formation of polySUMO chains by expression of ectopic human SUMO3 has a deleterious effect in Drosophila. These findings contribute to the understanding of the functional consequences of the evolution of SUMO genes. PMID- 26538143 TI - Acute hemodynamic effects of adaptive servoventilation in patients with pre capillary and post-capillary pulmonary hypertension. AB - RATIONALE: The hemodynamic effects of adaptive servoventilation (ASV) in patients with pulmonary hypertension (PH) are unknown. METHODS: A series of clinically stable patients with pre- or post-capillary PH underwent ASV therapy (endexpiratory positive airway pressure support 12-14 cm H2O, pressure support 4 10 cm H2O) during right heart catheterization. Hemodynamics were measured at rest, at the end of a 15-min episode of ASV therapy, and 15 min after ASV completion. Hemodynamic variables included heart rate, blood pressure, right atrial pressure (RAP), mean pulmonary artery pressure (PAPm), pulmonary arterial wedge pressure (PAWP), cardiac output and pulmonary vascular resistance (PVR). RESULTS: The study enrolled 33 patients; 12 patients with post-capillary PH due to heart failure with preserved ejection fraction, and 21 patients with pre capillary PH due to pulmonary arterial hypertension (n = 8) or chronic thromboembolic pulmonary hypertension (n = 13). ASV was well tolerated by all patients and resulted in reductions in systolic blood pressure (-8 mmHg, p = 0.01), PAPm (-5 mmHg, p <0.001) and PVR (-10%, p = 0.01). Right and left filling pressure increased, while the cardiac output decreased (-0.4 L/min; p < 0.001). The hemodynamic effects of ASV were similar in both patient populations. CONCLUSIONS: ASV had moderate hemodynamic effects in patients with PH of various origins, most importantly a decline in systolic blood pressure, PAPm and cardiac output. ASV was safe and well tolerated during this short-term study, but the observed drop in blood pressure and cardiac output may be of concern if ASV is applied in patients with advanced PH and severely impaired right ventricular function. PMID- 26538144 TI - Doxorubicin and carboplatin trials in Tasmanian devils (Sarcophilus harrisii) with Tasmanian devil facial tumor disease. AB - The devil facial tumor disease (DFTD) is having a devastating impact on Tasmanian devils (Sarcophilus harrisii) (devils) in the wild. Only a single study has been published regarding treatment of DFTD, where vincristine was not found to be an effective chemotherapeutic agent. In the current study, devils were treated with escalating dosages of carboplatin (8-26 mg/kg) (n = 13) and doxorubicin (0.75-1.0 mg/kg) (n = 5). Dosages for carboplatin (20 mg/kg) and doxorubicin (1.0 mg/kg) were identified as maximally tolerated dosages. Limiting toxicities for carboplatin were anorexia and weight loss (gastrointestinal signs) and azotemia. Limiting toxicities for doxorubicin were neutropenia, anorexia and weight loss. None of the treated devils responded to either drug, suggesting that, based on the clonality of this tumour, it is unlikely that either drug individually or in combination would be effective treatments for DFTD. These results, however, provide valuable information for practitioners who may choose to treat other neoplastic diseases in the devil or other marsupials. In addition, these results show that even drugs that are metabolized and excreted in the same manner can be tolerated to different degrees by the same species. PMID- 26538146 TI - Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons. AB - Peripheral purinergic signaling plays an important role in nociception. Increasing evidence suggests that metabotropic P2Y receptors are also involved, but little is known about the underlying mechanism. Herein, we report that selective P2Y receptor agonist uridine 5'-triphosphate (UTP) can exert an enhancing effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglia (DRG) neurons. First, UTP dose-dependently increased the amplitude of ASIC currents. UTP also shifted the concentration-response curve for proton upwards, with a 56.6 +/- 6.4% increase of the maximal current response to proton. Second, UTP potentiation of proton-gated currents can be mimicked by adenosine 5'-triphosphate (ATP), but not by P2Y1 receptor agonist ADP. Potentiation of UTP was blocked by P2Y receptor antagonist suramin and by inhibition of intracellular G protein, phospholipase C (PLC), protein kinase C (PKC), or protein interacting with C-kinase 1 (PICK1) signaling. Third, UTP altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, UTP dose-dependently exacerbated nociceptive responses to injection of acetic acid in rats. These results suggest that UTP enhanced ASIC-mediated currents and nociceptive responses, which reveal a novel peripheral mechanism underlying UTP-sensitive P2Y2 receptor involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons. PMID- 26538147 TI - PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts. AB - INTRODUCTION: Prostaglandin E receptor 4 (PTGER4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze its role in radiological joint damage in rheumatoid arthritis (RA). METHODS: Six independent cohorts of patients with RA of European or North American descent were included, comprising 1789 patients with 5083 sets of X-rays. The Hospital Clinico San Carlos Rheumatoid Arthritis, Princesa Early Arthritis Register Longitudinal study, and Hospital Universitario de La Paz early arthritis (Spain) cohorts were used as discovery cohorts, and the Leiden Early Arthritis Clinic (The Netherlands), Wichita (United States), and National Databank for Rheumatic Diseases (United States and Canada) cohorts as replication cohorts. First, the PTGER4 rs6896969 single-nucleotide polymorphism (SNP) was genotyped using TaqMan assays and available Illumina Immunochip data and studied in the discovery and replication cohorts. Second, the PTGER4 gene and adjacent regions were analyzed using Immunochip genotyping data in the discovery cohorts. On the basis of pooled p values, linkage disequilibrium structure of the region, and location in regions with transcriptional properties, SNPs were selected for replication. The results from discovery, replication, and overall cohorts were pooled using inverse variance-weighted meta-analysis. Influence of the polymorphisms on the overall radiological damage (constant effect) and on damage progression over time (time varying effect) was analyzed. RESULTS: The rs6896969 polymorphism showed a significant association with radiological damage in the constant effect pooled analysis of the discovery cohorts, although no significant association was observed in the replication cohorts or the overall pooled analysis. Regarding the analysis of the PTGER4 region, 976 variants were analyzed in the discovery cohorts. From the constant and time-varying effect analyses, 12 and 20 SNPs, respectively, were selected for replication. Only the rs76523431 variant showed a significant association with radiographic progression in the time-varying effect pooled analysis of the discovery, replication, and overall cohorts. The overall pooled effect size was 1.10 (95 % confidence interval 1.05-1.14, p = 2.10 * 10( 5)), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele. CONCLUSIONS: The PTGER4 gene is a candidate risk factor for radiological progression in RA. PMID- 26538148 TI - Intermediate-risk patients with three to four small adenomas should be considered low risk for colorectal cancer screening. AB - BACKGROUND AND AIM: Intermediate-risk patients following a colorectal cancer screening program may have differential risk of advanced lesions depending on the findings of an index colonoscopy. The aim of the present study was to comparatively assess advanced colorectal neoplasia risk at the first follow-up colonoscopy among the different intermediate-risk subgroups with a focus on patients with three to four adenomas. METHODS: All patients recruited for a baseline screening colonoscopy between 2006 and 2011 were included. Number, size and histopathological characteristics of adenomas were collected. Main outcome was an advanced colorectal neoplasia detection rate (invasive carcinoma or advanced adenoma) at the first follow-up colonoscopy. Low- and high-risk patients were excluded. RESULTS: Five hundred and sixty-one intermediate-risk patients (63.3% men, mean age: 59.01 +/- 6.16 years) underwent indexing and follow-up colonoscopy. By multivariate analysis, three to four adenomas (OR: 3.613 [95% CI: 1.661-7.859], P = 0.001) and adenoma size >=10 <20 mm (OR: 3.374 [95% CI: 1.618 7.034], P = 0.001) were independent factors associated with advanced colorectal neoplasia. Advanced lesions were detected in 7.66% of cases. Of patients with advanced colorectal neoplasia, 51.16% belonged to the three-to-four-adenoma group and >=1 of >=10 <20-mm subgroups (n = 132, 23.53%). These patients demonstrated a higher rate of advanced lesions [OR: 3.886 (95% CI: 2.061-7.325), P < 0.001] than patients with three to four small adenomas of <10 mm (16.67% vs 5.07%, P < 0.001). The association between patients with small adenomas (n = 217, 38.68%) and advanced lesions was not significant (OR: 0.521 [95% CI: 0257-1.056], P = 0.066). CONCLUSION: Intermediate-risk patients with three to four small adenomas achieved a very low advanced lesion rate at follow up. Surveillance interval should be lengthened because these patients should be considered low risk. PMID- 26538149 TI - Viral gene transfer of APPsalpha rescues synaptic failure in an Alzheimer's disease mouse model. AB - Alzheimer's disease (AD) is characterized by synaptic failure, dendritic and axonal atrophy, neuronal death and progressive loss of cognitive functions. It is commonly assumed that these deficits arise due to beta-amyloid accumulation and plaque deposition. However, increasing evidence indicates that loss of physiological APP functions mediated predominantly by neurotrophic APPsalpha produced in the non-amyloidogenic alpha-secretase pathway may contribute to AD pathogenesis. Upregulation of APPsalpha production via induction of alpha secretase might, however, be problematic as this may also affect substrates implicated in tumorigenesis. Here, we used a gene therapy approach to directly overexpress APPsalpha in the brain using AAV-mediated gene transfer and explored its potential to rescue structural, electrophysiological and behavioral deficits in APP/PS1?E9 AD model mice. Sustained APPsalpha overexpression in aged mice with already preexisting pathology and amyloidosis restored synaptic plasticity and partially rescued spine density deficits. Importantly, AAV-APPsalpha treatment also resulted in a functional rescue of spatial reference memory in the Morris water maze. Moreover, we demonstrate a significant reduction of soluble Abeta species and plaque load. In addition, APPsalpha induced the recruitment of microglia with a ramified morphology into the vicinity of plaques and upregulated IDE and TREM2 expression suggesting enhanced plaque clearance. Collectively, these data indicate that APPsalpha can mitigate synaptic and cognitive deficits, despite established pathology. Increasing APPsalpha may therefore be of therapeutic relevance for AD. PMID- 26538150 TI - Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau. AB - Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer's disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7-18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243-406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau. PMID- 26538151 TI - Nodular lymphocyte predominant Hodgkin lymphoma: Clincopathological study of 25 cases from Japan with a reappraisal of tissue associated macrophages. AB - Clinicopathological features of 25 nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) patients in Japan were analysed. To investigate the clinicopathological significance of tissue associated macrophages (TAM) in NLPHL, CD68 and CD163 expression were investigated. The median age at onset was 56 years (range: 6-82 years) with male predominance (64%). All patients presented with lymph node enlargement with predilection for cervical LNs. Seven cases (28%) had mediastinal lesion and four (16%) had extranodal involvement. Most cases (76%) presented with early clinical stages. After median follow up of 44 months, both of overall and progression free survival rates were 95%. The presence of >5% CD68+ TAM in NLPHL was significantly associated with older age at diagnosis (median, 71 vs 52.5 years; P = 0.048), lower hemoglobin level (33.3% vs 0%; P = 0.037) and lower CR rate after initial treatment (42.9% vs 91.7%; P = 0.038). The presence of >5% CD163+ TAM was significantly correlated with presence of B symptoms (40% vs 0%; P = 0.036). In conclusion, NLPHL is rare among Japanese and appears to present at an older age than among Western patients. In our series, the presence of >5% CD68+ TAM in NLPHL was associated with lower CR rate, but with no impact on patients' survival. PMID- 26538152 TI - Evolution and characterization of a benzylguanine-binding RNA aptamer. AB - Repurposing the "protein-labeling toolkit" for RNA research could be a pragmatic approach for developing new RNA-labeling methods. We have evolved an RNA aptamer that tightly binds benzylguanine (bG), the key ligand for the protein SNAP-tag. The aptamer tightly binds bG fluorophores and can be purified from cellular RNA with bG agarose under native conditions. PMID- 26538153 TI - The spatial distribution, accumulation and potential source of seldom monitored trace elements in sediments of Three Gorges Reservoir, China. AB - The alteration of hydrologic condition of Three Gorges Reservoir (TGR) after impoundment has caused numerous environmental changes. This study investigated the distribution, accumulation and potential sources of the seldom monitored trace elements (SMTEs) in sediments from three tributaries (ZY, MX and CT) and one mainstream (CJ) in TGR during different seasons. The average contents of most SMTEs excluding Sb in the winter were similar to that in the summer. For Sb, its average concentrations in the summer and winter were roughly six and three times higher than its background value, respectively. Contamination factor (CF) and geoaccumulation index (Igeo) demonstrated that most of the sediments were obviously contaminated by Sb. The enrichment factors (EF) of Ga and Sb were higher than 2.0, revealing the possible anthropogenic inputs; However, the EFs of other SMTEs were lower than 1.5, indicating the natural inputs. Correlation and principal component analysis suggested the most SMTEs were positively correlated with major elements (Cr, Mn, Cu, Zn, As, Cd and Pb) and clay contents, which implies that SMTEs had the same sources with these major metals, and the fine particles might be a major carrier for transporting SMTEs from the rivers to the TGR. PMID- 26538154 TI - Favourable outcome of posterior decompression and stabilization in lordosis for cervical spondylotic myelopathy: the spinal cord "back shift" concept. AB - PURPOSE: Surgical management of patients with multilevel CSM aims to decompress the spinal cord and restore the normal sagittal alignment. The literature lacks of high level evidences about the best surgical approach. Posterior decompression and stabilization in lordosis allows spinal cord back shift, leading to indirect decompression of the anterior spinal cord. The purpose of this study was to investigate the efficacy of posterior decompression and stabilization in lordosis for multilevel CSM. METHODS: 36 out of 40 patients were clinically assessed at a mean follow-up of 5, 7 years. Outcome measures included EMS, mJOA Score, NDI and SF-12. Patients were asked whether surgery met their expectations and if they would undergo the same surgery again. Bone graft fusion, instrumental failure and cervical curvature were evaluated. Spinal cord back shift was measured and correlation with EMS and mJOA score recovery rate was analyzed. RESULTS: All scores showed a significative improvement (p < 0.001), except the SF12-MCS (p > 0.05). Ninety percent of patients would undergo the same surgery again. There was no deterioration of the cervical alignment, posterior grafted bones had completely fused and there were no instrument failures. The mean spinal cord back shift was 3.9 mm (range 2.5-4.5 mm). EMS and mJOA recovery rates were significantly correlated with the postoperative posterior cord migration (P < 0.05). CONCLUSIONS: Posterior decompression and stabilization in lordosis is a valuable procedure for patients affected by multilevel CSM, leading to significant clinical improvement thanks to the spinal cord back shift. Postoperative lordotic alignment of the cervical spine is a key factor for successful treatment. PMID- 26538155 TI - Equal contributions and credit: an emerging trend in the characterization of authorship in major spine journals during a 10-year period. AB - PURPOSE: The practice of giving certain authors equal credit in scientific publications has become increasingly common in some medical specialties. However, whether this trend also exists in major spine journals remains unclear. This study aimed to investigate the prevalence and characteristics of the practice of giving authors equal credit in major spine journals. METHODS: Manual searches were performed to identify original research articles with equally credited authors (ECA) published between January 1, 2004 and December 31, 2013 in three major spine journals: Spine, European Spine Journal, and The Spine Journal. The number of authors with ECA and their positions in the byline, total number of authors, year of publication, and country of origin were analysed. RESULTS: The practice of ECA was found in all three journals. Articles with ECA comprised a greater proportion of the total number of publications in each journal in 2013 versus 2004 (Spine, 7.2 vs. 0.2%; European Spine Journal, 7.5 vs. 0.0%; and The Spine Journal, 6.2 vs. 0.0%). There was a statistically significant increasing trend in the annual proportion of papers with ECA for all three spine journals (p < 0.0001). The practice of ECA was applied in nearly every position in the byline, and the first two authors received equal credit in most cases. Articles with ECA were published by authors from various countries and regions around the world. However, none of the three spine journals provided specific guidance on this practice in their author instructions. CONCLUSIONS: The practice of ECA in original research articles is increasingly common in major spine journals. A guideline for authors regarding when and how to designate equal credit is warranted in the future. PMID- 26538156 TI - Evaluation of the predictors of postoperative aggravation of shoulder imbalance in severe and rigid thoracic or thoracolumbar scoliosis. AB - OBJECTIVE: To study the predictors of postoperative aggravation of shoulder imbalance in severe and rigid thoracic or thoracolumbar scoliosis. METHODS: In this study, 49 patients with severe and rigid thoracic or thoracolumbar scoliosis were analyzed retrospectively. The patients underwent whole-spine anteroposterior and lateral radiography preoperatively and postoperatively. On the radiographs, we measured parameters, including T1 tilt, radiographic shoulder height (RSH), proximal curve, middle curve, distal curve, apical vertebral translation (AVT) of the middle curve, thoracic trunk shift (TTS), coronal balance, and sagittal balance. We regarded RSH and T1 tilt as postoperative shoulder balance parameters and divided the patients into improved and aggravated groups of shoulder imbalance. Univariate analysis, receiver operating characteristic (ROC) curve, and multivariate logistic regression analyses were used in the statistical analyses. RESULTS: The RSH was -17.01 +/- 21.85 mm before surgery and 4.76 +/- 18.11 mm at follow-up. The T1 tilt angle was -10.20 degrees +/- 19.53 degrees before surgery and -2.72 degrees +/- 13.48 degrees at follow-up. The results of the univariate analysis suggest that preoperative RSH and proximal to middle curve change ratio were significantly higher in the patients in the improved RSH group (p < 0.01). In addition, preoperative RSH, preoperative T1 tilt, and apical vertebral translation of the middle curve were significantly higher, and preoperative proximal curve, postoperative proximal curve, and preoperative distal curve were significantly lower in the patients with improved T1 tilt group (p < 0.01). In a binary logistic regression analysis, preoperative RSH [B = 0.120, odds ratio (OR) = 0.887, p = 0.006] was found to be an independent predictor of postoperative aggravation of RSH. Similarly, preoperative T1 tilt (B = -0.488, OR = 0.614, p = 0.001) was found to be an independent predictor of postoperative aggravation of T1 tilt. Moreover, the relationship between changes in RSH and T1 tilt was either concordant or discordant. CONCLUSION: Several radiographic parameters were found to affect postoperative aggravation of RSH and T1 tilt. In particular, preoperative RSH and T1 tilt were found to be independent predictive factors of postoperative aggravation of RSH and T1 tilt, respectively. PMID- 26538157 TI - Acute benign vertebral compression fractures: "see-through sign" on contrast enhanced MR images. AB - PURPOSE: To retrospectively evaluate the diagnostic role of the contrast-enhanced MRI (CE-MRI) for differentiation between benign VCFs and malignant VCFs focusing on the internal transparent trabecular bone on CE-MRI (the "see-through sign"). MATERIALS AND METHODS: The institutional review board approved this study and informed consent was waived due to the retrospective nature of the study. From January 2012 to December 2013, all 149 consecutive benign or malignant VCF patients were enrolled for consideration in this study from a CE-MRI database. In the first analysis, four radiologists independently evaluated the presence or absence of the see-through sign. The see-through sign was defined as internal transparent trabecular bone morphology on CE-MRI. The intraclass correlation coefficient (ICC), percentage agreement, and Fleiss's kappa statistics were obtained. RESULTS: Fifty-seven patients (M:F = 27:30; mean age, 63 years; age range, 20-88 years) who diagnosed as acute benign (n = 24) and malignant (n = 33) VCFs were finally included for the analysis. The results of all readers showed that the see-through sign was associated with acute benign VCFs (p < 0.05). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the see-through sign ranged from 75-96, 70-88, 66-85, 81-97 %, respectively. The inter-observer reliability of the see-through sign was sufficient with ICC = 0.847, percentage agreement = 78.9, and kappa = 0.578. CONCLUSION: The see-through sign on CE-MRI is featured in acute benign VCFs, and it can be a useful finding to differentiate between benign and malignant VCFs. PMID- 26538158 TI - Pelvic incidence: an anatomic investigation of 880 cadaveric specimens. AB - PURPOSE: Pelvic incidence is a position- and posture-independent parameter used to quantify sagittal balance of the spine, sacrum, pelvis and hips. Its functional consequences have been associated with a number of different pathologies of the spine. However, there exists considerable controversy over which demographic features contribute to the development of pelvic incidence. METHODS: 880 cadaveric skeletons from the Hamann-Todd Osteological Collection were obtained. The innominate bones and sacrum were reconstructed, and pelvic incidence was measured using a previously validated technique. Specimens with obvious fracture, infection, or rheumatologic conditions were excluded from study. Descriptive data of age at the time of death, gender, race and height were collected. RESULTS: The average pelvic incidence was 46.0 degrees +/- 11.0 degrees . Pelvic incidence did not change with age (r = 0.026, p = 0.288). There was no difference in pelvic incidence measurements between females and males (47.2 degrees +/- 13.8 degrees vs. 45.8 degrees +/- 10.4 degrees , respectively; p = 0.257), although this analysis was under-powered. Pelvic incidence was higher in African-Americans compared to Caucasians (48.9 degrees +/- 11.0 degrees vs. 44.9 degrees +/- 10.8 degrees ; p = 0.001). There was no association between height and pelvic incidence (r = -0.042, p = 0.164). CONCLUSIONS: This study represents the largest single cohort of pelvic incidence measurements reported in the literature. Our data suggest that pelvic incidence does not change with age or height, although racial differences do exist. As spine care providers increasingly rely on pelvic incidence as an important means to quantify sagittal balance, the normative data provided herein will provide an essential reference. PMID- 26538159 TI - A multifunctional role of trialkylbenzenes for the preparation of aqueous colloidal mesostructured/mesoporous silica nanoparticles with controlled pore size, particle diameter, and morphology. AB - Both the pore size and particle diameter of aqueous colloidal mesostructured/mesoporous silica nanoparticles (CMSS/CMPS) derived from tetrapropoxysilane were effectively and easily controlled by the addition of trialkylbenzenes (TAB). Aqueous highly dispersed CMPS with large pores were successfully obtained through removal of surfactants and TAB by a dialysis process. The pore size (from 4 nm to 8 nm) and particle diameter (from 50 nm to 380 nm) were more effectively enlarged by the addition of 1,3,5 triisopropylbenzene (TIPB) than 1,3,5-trimethylbenzene (TMB), and the enlargement did not cause the variation of the mesostructure and particle morphology. The larger molecular size and higher hydrophobicity of TIPB than TMB induce the incorporation of TIPB into micelles without the structural change. When TMB was used as TAB, the pore size of CMSS was also enlarged while the mesostructure and particle morphology were varied. Interestingly, when tetramethoxysilane and TIPB were used, CMSS with a very small particle diameter (20 nm) with concave surfaces and large mesopores were obtained, which may strongly be related to the initial nucleation of CMSS. A judicious choice of TAB and Si sources is quite important to control the mesostructure, size of mesopores, particle diameter, and morphology. PMID- 26538160 TI - Interdisciplinary Treatment of Maladaptive Behaviors Associated with Postural Orthostatic Tachycardia Syndrome (POTS): A Case Report. AB - The prevalence of postural orthostatic tachycardia syndrome (POTS) in adolescents and young adults has been increasing during the past decade. Despite this increase, documentation regarding treatment of these patients is just beginning to emerge. In addition, despite a call for a multidisciplinary or interdisciplinary approach, no studies have examined the efficacy of such an approach to treatment. This paper describes a case study of a 19-year-old male with debilitating POTS seen at a tertiary clinic for evaluation and subsequent intensive interdisciplinary treatment. The treatment approach is described and outcomes are presented. PMID- 26538161 TI - Was the increase in culture-confirmed Campylobacter infections in Denmark during the 1990s a surveillance artefact? AB - In 1991, 1999 and 2006, randomly selected individuals from the Danish Central Personal Register provided a serum sample. From individuals aged 30 years and above, 500 samples from each year were analysed for Campylobacter IgG, IgA and IgM antibodies using a direct ELISA method. We applied a seroincidence calculator available from the European Centre for Disease Prevention and Control to perform a mathematical back-calculation to estimate the annual Campylobacter seroincidence in the Danish population. The estimated Campylobacter seroincidence did not differ significantly between the 1991, 1999 and 2006 studies although the reported number of culture-confirmed cases of Campylobacter infection increased 2.5 fold from 1993 to 1999 among individuals aged 30 years and above. This suggests that Campylobacter was widely present in the Danish population before the increase in poultry-associated clinical Campylobacter infections observed from 1993 to 2001 among individuals of this age groups. PMID- 26538162 TI - Rhodium-Catalyzed C-S and C-N Functionalization of Arenes: Combination of C-H Activation and Hypervalent Iodine Chemistry. AB - Rhodium-catalyzed sulfonylation, thioetherification, thiocyanation, and other heterofunctionalizations of arenes bearing a heterocyclic directing group have been realized. The reaction proceeds by initial Rh(III) -catalyzed C-H hyperiodination of arene at room temperature followed by uncatalyzed nucleophilic functionalization. A diaryliodonium salt is isolated as an intermediate, which represents umpolung of the arene substrate, in contrast to previous studies that suggested umpolung of the coupling partner. PMID- 26538163 TI - Adherence to Brain Trauma Foundation guidelines for management of traumatic brain injury patients: study protocol for a systematic review and meta-analysis. AB - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability around the world. Management based on Brain Trauma Foundation (BTF) guidelines is widely accepted and thought to improve outcome. The objectives of this systematic review are to give an overview of adherence to the BTF guidelines, describe factors influencing adherence, and study the effect of guideline-based management on outcome. METHODS/DESIGN: We will search electronic bibliographic databases: PROSPERO, Medline, EMBASE, SCOPUS, NHS, CINAHL, Cochrane Database, and ProQuest Dissertations and Theses Global. Two investigators will independently screen all titles, abstracts, and articles and select Randomized Controlled Trial (RCT), cohort studies, case-control studies, and case series reporting the adherence rate, factors influencing adherence, and mortality or morbidity. These investigators will also independently extract data using a pre designed and pilot-tested standardized electronic data extraction form and assess the risk of bias. We will exclude pediatric and military-related TBI studies, studies that included fewer than ten patients or addressed adherence to pre hospital guidelines. Narrative synthesis and if appropriate, quantitative meta analysis clustered by type of recommendation will be reported. DISCUSSION: This study is expected to demonstrate the current level of professionals' adherence to BTF guidelines in patients with severe traumatic brain injury, it will describe the factors influencing adherence, which may provide valuable input for development of strategies to successfully increase adherence. In addition, if the studies are sufficiently homogenous, it will describe the effect of these guidelines on patient outcome. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017794. PMID- 26538164 TI - Temperature dependence of Coulomb oscillations in a few-layer two-dimensional WS2 quantum dot. AB - Standard semiconductor fabrication techniques are used to fabricate a quantum dot (QD) made of WS2, where Coulomb oscillations were found. The full-width-at-half maximum of the Coulomb peaks increases linearly with temperature while the height of the peaks remains almost independent of temperature, which is consistent with standard semiconductor QD theory. Unlike graphene etched QDs, where Coulomb peaks belonging to the same QD can have different temperature dependences, these results indicate the absence of the disordered confining potential. This difference in the potential-forming mechanism between graphene etched QDs and WS2 QDs may be the reason for the larger potential fluctuation found in graphene QDs. PMID- 26538165 TI - IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma. AB - The recent identification of IDH mutations in gliomas and several other cancers suggests that this pathway is involved in oncogenesis; however effector functions are complex and yet incompletely understood. To study the regulatory effects of IDH on hypoxia-inducible-factor 1-alpha (HIF1A), a driving force in hypoxia initiated angiogenesis, we analyzed mRNA expression profiles of 288 glioma patients and show decreased expression of HIF1A targets on a single-gene and pathway level, strong inhibition of upstream regulators such as HIF1A and downstream biological functions such as angio- and vasculogenesis in IDH mutant tumors. Genotype/imaging phenotype correlation analysis with relative cerebral blood volume (rCBV) MRI - a robust and non-invasive estimate of tumor angiogenesis - in 73 treatment-naive patients with low-grade and anaplastic gliomas showed that a one-unit increase in rCBV corresponded to a two-third decrease in the odds for an IDH mutation and correctly predicted IDH mutation status in 88% of patients. Together, these findings (1) show that IDH mutation status is associated with a distinct angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging and (2) highlight the potential future of radiogenomics (i.e. the correlation between cancer imaging and genomic features) towards a more accurate diagnostic workup of brain tumors. PMID- 26538166 TI - The clinician in the university: Reflections on a South African psychoanalytically oriented doctoral programme. AB - There is increasing interest, both internationally and in South Africa, in strengthening the relationship between psychoanalytic practice and research. This paper reports on a psychoanalytically oriented doctoral programme offered at the University of the Witwatersrand in South Africa. The programme is described in relation to the broader context of the historical relationship of psychoanalysis to the university as well as to the specific context of the history of psychoanalysis in South Africa. Key challenges of the programme, specifically concerning research tensions and methodological and theoretical tolerance, are subsequently explored. The way in which these challenges manifested within a group context illustrates their potential for conflict as well as productive debate. The paper reflects on how this specific programme illuminates and extends some of the broader debates in the field of psychoanalysis. PMID- 26538167 TI - Tissue Contraction Force Microscopy for Optimization of Engineered Cardiac Tissue. AB - We developed a high-throughput screening assay that allows for relative comparison of the twitch force of millimeter-scale gel-based cardiac tissues. This assay is based on principles taken from traction force microscopy and uses fluorescent microspheres embedded in a soft polydimethylsiloxane (PDMS) substrate. A gel-forming cell suspension is simply pipetted onto the PDMS to form hemispherical cardiac tissue samples. Recordings of the fluorescent bead movement during tissue pacing are used to determine the maximum distance that the tissue can displace the elastic PDMS substrate. In this study, fibrin gel hemispheres containing human induced pluripotent stem cell-derived cardiomyocytes were formed on the PDMS and allowed to culture for 9 days. Bead displacement values were measured and compared to direct force measurements to validate the utility of the system. The amplitude of bead displacement correlated with direct force measurements, and the twitch force generated by the tissues was the same in 2 and 4 mg/mL fibrin gels, even though the 2 mg/mL samples visually appear more contractile if the assessment were made on free-floating samples. These results demonstrate the usefulness of this assay as a screening tool that allows for rapid sample preparation, data collection, and analysis in a simple and cost effective platform. PMID- 26538168 TI - The evolution of aquatic feeding in seals: insights from Enaliarctos (Carnivora: Pinnipedimorpha), the oldest known seal. AB - The development of pierce-feeding and loss of oral processing represented major adaptations for underwater feeding in marine mammals. We examined the evolution of pierce-feeding and its association with changes in tooth spacing and tooth size to determine whether pierce-feeding was practiced by the earliest known pinnipeds. Data on crown size and spacing in postcanine dentition were collected and 1) analysed by principal components analysis (PCA) to determine the tooth morphospace of arctoid carnivores, 2) analysed by least squares (LS) regression and phylogenetic independent contrasts (PIC) to determine what morphological variables were associated with increases in tooth spacing, and 3) used to reconstruct the evolution of feeding related traits within a phylogenetic context. The PCA analysis revealed that within arctoid carnivores, the greatest differences in morphospace were associated with pierce-feeding, and the early diverging seal Enaliarctos was placed within the pinniped morphospace. Increased tooth spacing within Pinnipedia is a result of decreased postcanine crown size. When the evolution of dental characters is reconstructed, 'enaliarctines' were found to represent an intermediate stage in evolution between 'fissiped' and pinniped carnivores. They retained the limited tooth spacing of terrestrial carnivores, possessed postcanine crown lengths intermediate in size between pinnipeds and fissipeds, and possessed reduced heterodonty characteristic of crown pinnipeds. Our study indicated that pierce-feeding evolved early within pinnipeds. This suggested either that pierce-feeding evolved prior to the loss of mastication, or that pierce-feeding evolved at the same time as loss of mastication, and well before simplification of the dentition was completed. PMID- 26538170 TI - Death rates have risen sharply among middle aged white people in the US, study finds. PMID- 26538169 TI - Low birth weight in a sub-urban area of Cameroon: an analysis of the clinical cut off, incidence, predictors and complications. AB - BACKGROUND: The World Health Organisation recommends that each country adopts its own cut-off value of low birth weight (LBW) for clinical use. The aims of this study were to establish a clinical cut-off point for LBW and to determine its incidence, predictors and complications in a sub-urban area's hospital of Cameroon. METHODS: We conducted a study in two phases: a 6-year retrospective phase during which we collected demographic and clinical information from the records of the maternity of the Buea Regional Hospital (BRH) and a 3-month prospective phase during which data were collected from consenting pregnant women using a structured questionnaire, and newborns were examined and followed after birth. RESULTS: A total of 4941 records were reviewed during the retrospective phase and the 10(th) centile of birth weights was 2600 g. In the 200 pregnant women enrolled during the prospective phase, using this cut-off yielded an incidence of LBW of 19.0 %. Independent predictors of LBW were preterm delivery, hypertensive disorders in pregnancy, HIV infection, maternal age >36 years, maternal height <150 cm and pre-delivery BMI < 25 kg/m(2). Neonates with LBW were more likely to have neonatal asphyxia, foetal distress, respiratory distress and neonatal death. CONCLUSIONS: Our results suggest that newborns under 2600 g have LBW in sub-urban Cameroon. They represent one out of every five babies, and they deserve close care. Preventive measures targeting the predictors described here are warranted to reduce the incidence and complications. Similar studies in urban areas are required in order to generalize the results. PMID- 26538171 TI - Supporting biologists, inspiring biology. PMID- 26538172 TI - A classic model animal in the 21st century: recent lessons from the leech nervous system. AB - The medicinal leech (genus Hirudo) is a classic model animal in systems neuroscience. The leech has been central to many integrative studies that establish how properties of neurons and their interconnections give rise to the functioning of the animal at the behavioral level. Leeches exhibit several discrete behaviors (such as crawling, swimming and feeding) that are each relatively simple. Importantly, these behaviors can all be studied - at least at a basal level - in the isolated nervous system. The leech nervous system is particularly amenable to such studies because of its distributed nature; sensory processing and generation of behavior occur to a large degree in iterated segmental ganglia that each contain only ~400 neurons. Furthermore, the neurons are relatively large and are arranged with stereotyped topography on the surface of the ganglion, which greatly facilitates their identification and accessibility. This Commentary provides an overview of recent work on the leech nervous system, with particular focus on circuits that underlie leech behavior. Studies that combine the unique features of the leech with modern optical and genetic techniques are also discussed. Thus, this Commentary aims to explain the continued appeal of the leech as an experimental animal in the 21st century. PMID- 26538173 TI - Robust jumping performance and elastic energy recovery from compliant perches in tree frogs. AB - Arboreal animals often move on compliant branches, which may deform substantially under loads, absorbing energy. Energy stored in a compliant substrate may be returned to the animal or it may be lost. In all cases studied so far, animals jumping from a static start lose all of the energy imparted to compliant substrates and performance is reduced. Cuban tree frogs (Osteopilus septentrionalis) are particularly capable arboreal jumpers, and we hypothesized that these animals would be able to recover energy from perches of varying compliance. In spite of large deflections of the perches and consequent substantial energy absorption, frogs were able to regain some of the energy lost to the perch during the recoil. Takeoff velocity was robust to changes in compliance, but was lower than when jumping from flat surfaces. This highlights the ability of animals to minimize energy loss and maintain dependable performance on challenging substrates via behavioral changes. PMID- 26538174 TI - Chemical cues from fish heighten visual sensitivity in larval crabs through changes in photoreceptor structure and function. AB - Several predator avoidance strategies in zooplankton rely on the use of light to control vertical position in the water column. Although light is the primary cue for such photobehavior, predator chemical cues or kairomones increase swimming responses to light. We currently lack a mechanistic understanding for how zooplankton integrate visual and chemical cues to mediate phenotypic plasticity in defensive photobehavior. In marine systems, kairomones are thought to be amino sugar degradation products of fish body mucus. Here, we demonstrate that increasing concentrations of fish kairomones heightened sensitivity of light mediated swimming behavior for two larval crab species (Rhithropanopeus harrisii and Hemigrapsus sanguineus). Consistent with these behavioral results, we report increased visual sensitivity at the retinal level in larval crab eyes directly following acute (1-3 h) kairomone exposure, as evidenced electrophysiologically from V-log I curves and morphologically from wider, shorter rhabdoms. The observed increases in visual sensitivity do not correspond with a decline in temporal resolution, because latency in electrophysiological responses actually increased after kairomone exposure. Collectively, these data suggest that phenotypic plasticity in larval crab photobehavior is achieved, at least in part, through rapid changes in photoreceptor structure and function. PMID- 26538175 TI - Effects of stride frequency and foot position at landing on braking force, hip torque, impact peak force and the metabolic cost of running in humans. AB - Endurance runners are often advised to use 90 strides min(-1), but how optimal is this stride frequency and why? Endurance runners are also often advised to maintain short strides and avoid landing with the feet too far in front of their hips or knees (colloquially termed 'overstriding'), but how do different kinematic strategies for varying stride length at the same stride frequency affect economy and impact peaks? Linear mixed models were used to analyze repeated measures of stride frequency, the anteroposterior position of the foot at landing, VO2 , lower extremity kinematics and vertical ground reaction forces in 14 runners who varied substantially in height and body mass and who were asked to run at 75, 80, 85, 90 and 95 strides min(-1) at 3.0 m s(-1). For every increase of 5 strides min(-1), maximum hip flexor moments in the sagittal plane increased by 5.8% (P<0.0001), and the position of the foot at landing relative to the hip decreased by 5.9% (P=0.003). Higher magnitudes of posteriorly directed braking forces were associated with increases in foot landing position relative to the hip (P=0.0005) but not the knee (P=0.54); increases in foot landing position relative to the knee were associated with higher magnitudes (P<0.0001) and rates of loading (P=0.07) of the vertical ground reaction force impact peak. Finally, the mean metabolically optimal stride frequency was 84.8+/-3.6 strides min(-1), with 50.4% of the variance explained by the trade-off between minimizing braking forces versus maximum hip flexor moments during swing. The results suggest that runners may benefit from a stride frequency of approximately 85 strides min(-1) and by landing at the end of swing phase with a relatively vertical tibia. PMID- 26538176 TI - Decreasing methane yield with increasing food intake keeps daily methane emissions constant in two foregut fermenting marsupials, the western grey kangaroo and red kangaroo. AB - Fundamental differences in methane (CH4) production between macropods (kangaroos) and ruminants have been suggested and linked to differences in the composition of the forestomach microbiome. Using six western grey kangaroos (Macropus fuliginosus) and four red kangaroos (Macropus rufus), we measured daily absolute CH4 production in vivo as well as CH4 yield (CH4 per unit of intake of dry matter, gross energy or digestible fibre) by open-circuit respirometry. Two food intake levels were tested using a chopped lucerne hay (alfalfa) diet. Body mass specific absolute CH4 production resembled values previously reported in wallabies and non-ruminant herbivores such as horses, and did not differ with food intake level, although there was no concomitant proportionate decrease in fibre digestibility with higher food intake. In contrast, CH4 yield decreased with increasing intake, and was intermediate between values reported for ruminants and non-ruminant herbivores. These results correspond to those in ruminants and other non-ruminant species where increased intake (and hence a shorter digesta retention in the gut) leads to a lower CH4 yield. We hypothesize that rather than harbouring a fundamentally different microbiome in their foregut, the microbiome of macropods is in a particular metabolic state more tuned towards growth (i.e. biomass production) rather than CH4 production. This is due to the short digesta retention time in macropods and the known distinct 'digesta washing' in the gut of macropods, where fluids move faster than particles and hence most likely wash out microbes from the forestomach. Although our data suggest that kangaroos only produce about 27% of the body mass-specific volume of CH4 of ruminants, it remains to be modelled with species-specific growth rates and production conditions whether or not significantly lower CH4 amounts are emitted per kg of meat in kangaroo than in beef or mutton production. PMID- 26538177 TI - Gas exchange and dive characteristics of the free-swimming backswimmer Anisops deanei. AB - Many aquatic insects utilise air bubbles on the surface of their bodies to supply O2 while they dive. The bubbles can simply store O2, as in the case of an 'air store', or they can act as a physical 'gas gill', extracting O2 from the water. Backswimmers of the genus Anisops augment their air store with O2 from haemoglobin cells located in the abdomen. The O2 release from the haemoglobin helps stabilise bubble volume, enabling backswimmers to remain near neutrally buoyant for a period of the dive. It is generally assumed that the backswimmer air store does not act as a gas gill and that gas exchange with the water is negligible. This study combines measurements of dive characteristics under different exotic gases (N2, He, SF6, CO) with mathematical modelling, to show that the air store of the backswimmer Anisops deanei does exchange gases with the water. Our results indicate that approximately 20% of O2 consumed during a dive is obtained directly from the water. Oxygen from the water complements that released from the haemoglobin, extending the period of near-neutral buoyancy and increasing dive duration. PMID- 26538179 TI - Unusual Deep Water sponge assemblage in South China-Witness of the end-Ordovician mass extinction. AB - There are few sponges known from the end-Ordovician to early-Silurian strata all over the world, and no records of sponge fossils have been found yet in China during this interval. Here we report a unique sponge assemblage spanning the interval of the end-Ordovician mass extinction from the Kaochiapien Formation (Upper Ordovician-Lower Silurian) in South China. This assemblage contains a variety of well-preserved siliceous sponges, including both Burgess Shale-type and modern type taxa. It is clear that this assemblage developed in deep water, low energy ecosystem with less competitors and more vacant niches. Its explosion may be related to the euxinic and anoxic condition as well as the noticeable transgression during the end-Ordovician mass extinction. The excellent preservation of this assemblage is probably due to the rapid burial by mud turbidites. This unusual sponge assemblage provides a link between the Burgess Shale-type deep water sponges and the modern forms. It gives an excellent insight into the deep sea palaeoecology and the macroevolution of Phanerozoic sponges, and opens a new window to investigate the marine ecosystem before and after the end-Ordovician mass extinction. It also offers potential to search for exceptional fossil biota across the Ordovician-Silurian boundary interval in China. PMID- 26538182 TI - Optimal adaptive sequential designs for crossover bioequivalence studies. AB - In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at >= 80%, their average sample sizes were similar to or less than those of conventional single stage designs. PMID- 26538181 TI - Inward lithium-ion breathing of hierarchically porous silicon anodes. AB - Silicon has been identified as a highly promising anode for next-generation lithium-ion batteries (LIBs). The key challenge for Si anodes is large volume change during the lithiation/delithiation cycle that results in chemomechanical degradation and subsequent rapid capacity fading. Here we report a novel fabrication method for hierarchically porous Si nanospheres (hp-SiNSs), which consist of a porous shell and a hollow core. On charge/discharge cycling, the hp SiNSs accommodate the volume change through reversible inward Li breathing with negligible particle-level outward expansion. Our mechanics analysis revealed that such inward expansion is enabled by the much stiffer lithiated layer than the unlithiated porous layer. LIBs assembled with the hp-SiNSs exhibit high capacity, high power and long cycle life, which is superior to the current commercial Si based anode materials. The low-cost synthesis approach provides a new avenue for the rational design of hierarchically porous structures with unique materials properties. PMID- 26538180 TI - Boron-deficiency-responsive microRNAs and their targets in Citrus sinensis leaves. AB - BACKGROUND: MicroRNAs play important roles in the adaptive responses of plants to nutrient deficiencies. Most research, however, has focused on nitrogen (N), phosphorus (P), sulfur (S), copper (Cu) and iron (Fe) deficiencies, limited data are available on the differential expression of miRNAs and their target genes in response to deficiencies of other nutrient elements. In this study, we identified the known and novel miRNAs as well as the boron (B)-deficiency-responsive miRNAs from citrus leaves in order to obtain the potential miRNAs related to the tolerance of citrus to B-deficiency. METHODS: Seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] were supplied every other day with B-deficient (0 MUM H3BO3) or -sufficient (10 MUM H3BO3) nutrient solution for 15 weeks. Thereafter, we sequenced two small RNA libraries from B-deficient and -sufficient (control) citrus leaves, respectively, using Illumina sequencing. RESULTS: Ninety one (83 known and 8 novel) up- and 81 (75 known and 6 novel) down-regulated miRNAs were isolated from B-deficient leaves. The great alteration of miRNA expression might contribute to the tolerance of citrus to B-deficiency. The adaptive responses of miRNAs to B-deficiency might related to several aspects: (a) attenuation of plant growth and development by repressing auxin signaling due to decreased TIR1 level and ARF-mediated gene expression by altering the expression of miR393, miR160 and miR3946; (b) maintaining leaf phenotype and enhancing the stress tolerance by up regulating NACs targeted by miR159, miR782, miR3946 and miR7539; (c) activation of the stress responses and antioxidant system through down-regulating the expression of miR164, miR6260, miR5929, miR6214, miR3946 and miR3446; (d) decreasing the expression of major facilitator superfamily protein genes targeted by miR5037, thus lowering B export from plants. Also, B-deficiency-induced down regulation of miR408 might play a role in plant tolerance to B-deficiency by regulating Cu homeostasis and enhancing superoxide dismutase activity. CONCLUSIONS: Our study reveals some novel responses of citrus to B-deficiency, which increase our understanding of the adaptive mechanisms of citrus to B deficiency at the miRNA (post-transcriptional) level. PMID- 26538184 TI - Unraveling the complexity of the interactions of DNA nucleotides with gold by single molecule force spectroscopy. AB - Addressing the effect of different environmental factors on the adsorption of DNA to solid supports is critical for the development of robust miniaturized devices for applications ranging from biosensors to next generation molecular technology. Most of the time, thiol-based chemistry is used to anchor DNA on gold - a substrate commonly used in nanotechnology - and little is known about the direct interaction between DNA and gold. So far there have been no systematic studies on the direct adsorption behavior of the deoxyribonucleotides (i.e., a nitrogenous base, a deoxyribose sugar, and a phosphate group) and on the factors that govern the DNA-gold bond strength. Here, using single molecule force spectroscopy, we investigated the interaction of the four individual nucleotides, adenine, guanine, cytosine, and thymine, with gold. Experiments were performed in three salinity conditions and two surface dwell times to reveal the factors that influence nucleotide-Au bond strength. Force data show that, at physiological ionic strength, adenine-Au interactions are stronger, asymmetrical and independent of surface dwell time as compared to cytosine-Au and guanine-Au interactions. We suggest that in these conditions only adenine is able to chemisorb on gold. A decrease of the ionic strength significantly increases the bond strength for all nucleotides. We show that moderate ionic strength along with longer surface dwell period suggest weak chemisorption also for cytosine and guanine. PMID- 26538183 TI - In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration. AB - This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37+/-0.14 in comparison to 0.07+/-0.14 for the four control rats (p<0.01 ). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36+/-0.15 0.36+/ 0.15 in comparison to 0.14+/-0.24 of the control rats (0.0595 %). CONCLUSIONS: Prevalence and experience of odontogenic infections and the untreated caries-pufa ratio were increasing from the younger to the elder children. Dmft and pufa scores in primary teeth predict a higher caries risk in permanent teeth. The pufa index highlights relevant information for decision makers to develop effective oral health care programs for children at high risk for caries. PMID- 26538197 TI - Correction: Proteomic analysis of the copper resistance of Streptococcus pneumoniae. PMID- 26538198 TI - Fast T2 gradient-spin-echo (T2-GraSE) mapping for myocardial edema quantification: first in vivo validation in a porcine model of ischemia/reperfusion. AB - BACKGROUND: Several T2-mapping sequences have been recently proposed to quantify myocardial edema by providing T2 relaxation time values. However, no T2-mapping sequence has ever been validated against actual myocardial water content for edema detection. In addition, these T2-mapping sequences are either time consuming or require specialized software for data acquisition and/or post processing, factors impeding their routine clinical use. Our objective was to obtain in vivo validation of a sequence for fast and accurate myocardial T2 mapping (T2 gradient-spin-echo [GraSE]) that can be easily integrated in routine protocols. METHODS: The study population comprised 25 pigs. Closed-chest 40 min ischemia/reperfusion was performed in 20 pigs. Pigs were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5) and 7 days (n = 5) after reperfusion, and heart tissue extracted for quantification of myocardial water content. For the evaluation of T2 relaxation time, cardiovascular magnetic resonance (CMR) scans, including T2 turbo-spin-echo (T2-TSE, reference standard) mapping and T2-GraSE mapping, were performed at baseline and at every follow-up until sacrifice. Five additional pigs were sacrificed after baseline CMR study and served as controls. RESULTS: Acquisition of T2-GraSE mapping was significantly (3-fold) faster than conventional T2-TSE mapping. Myocardial T2 relaxation measurements performed by T2-TSE and T2-GraSE mapping demonstrated an almost perfect correlation (R(2) = 0.99) and agreement with no systematic error between techniques. The two T2 mapping sequences showed similarly good correlations with myocardial water content: R(2) = 0.75 and R(2) = 0.73 for T2-TSE and T2-GraSE mapping, respectively. CONCLUSIONS: We present the first in vivo validation of T2-mapping to assess myocardial edema. Given its shorter acquisition time and no requirement for specific software for data acquisition or post-processing, fast T2-GraSE mapping of the myocardium offers an attractive alternative to current CMR sequences for T2 quantification. PMID- 26538199 TI - Hepatotoxicity associated with the dietary supplement OxyELITE ProTM - Hawaii, 2013. AB - Dietary supplements are increasingly marketed to and consumed by the American public for a variety of purported health benefits. On 9 September 2013, the Hawaii Department of Health (HDOH) was notified of a cluster of acute hepatitis and fulminant hepatic failure among individuals with exposure to the dietary supplement OxyELITE ProTM (OEP). HDOH conducted an outbreak investigation in collaboration with federal partners. Physicians were asked to report cases, defined as individuals with acute onset hepatitis of unknown etiology on or after 1 April 2013, a history of weight-loss/muscle-building dietary supplement use during the 60 days before illness onset, and residence in Hawaii during the period of exposure. Reported cases' medical records were reviewed, questionnaires were administered, and a product investigation, including chemical analyses and traceback, was conducted. Of 76 reports, 44 (58%) met case definition; of these, 36 (82%) reported OEP exposure during the two months before illness. No other common supplements or exposures were observed. Within the OEP-exposed subset, two patients required liver transplantation, and a third patient died. Excessive product dosing was not reported. No unique lot numbers were identified; there were multiple mainland distribution points, and lot numbers common to cases in Hawaii were also identified in continental states. Product analysis found consumed products were consistent with labeled ingredients; the mechanism of hepatotoxicity was not identified. We report one of the largest statewide outbreaks of dietary supplement-associated hepatotoxicity. The implicated product was OEP. The increasing popularity of dietary supplements raises the potential for additional clusters of dietary supplement-related adverse events. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26538200 TI - Temperature effects on hatching and viability of Juvenile Gill Lice, Salmincola californiensis. AB - Salmonids of the genus Oncorhynchus, distributed throughout the Pacific Rim, can be infected by the gill lice species Salmincola californiensis (Dana, 1852), which makes them one of the most broadly distributed gill lice species. Despite their broad distribution and valuable obligate salmonid hosts, relatively little is known about S. californiensis. We evaluated effects of temperature on timing of S. californiensis hatching and survival of copepodids, and provide information on brood size and variability. Our results suggest that temperature was a primary driver of timing of S. californiensis hatching and post-hatching survival. Prior to this study, the free-swimming stage of S. californiensis was reported to survive approximately 2 days without a suitable host. We observed active copepodids 13 days after hatch with some individuals from most (>90%) viable egg sacs at all temperature treatments surviving >=5 days. Our findings indicate that warmer temperatures could increase development rates of gill lice at certain life stages, potentially increasing fecundity. This information coupled with predictions that warmer water temperatures could intensify crowding of coldwater fishes, stress, and parasite transmission suggests that climate change could exacerbate negative effects of S. californiensis on ecologically and economically important salmonids. PMID- 26538201 TI - Carbon nanodot decorated graphitic carbon nitride: new insights into the enhanced photocatalytic water splitting from ab initio studies. AB - Interfacing carbon nanodots (C-dots) with graphitic carbon nitride (g-C3N4) produces a metal-free system that has recently demonstrated significant enhancement of photo-catalytic performance for water splitting into hydrogen [Science, 2015, 347, 970-974]. However, the underlying photo-catalytic mechanism is not fully established. Herein, we have carried out density functional theory (DFT) calculations to study the interactions between g-C3N4 and trigonal/hexagonal shaped C-dots. We find that hybrid C-dots/g-C3N4 can form a type-II van der Waals heterojunction, leading to significant reduction of band gap. The C-dot decorated g-C3N4 enhances the separation of photogenerated electron and hole pairs and the composite's visible light response. Interestingly, the band alignment of C-dots and g-C3N4 calculated by the hybrid functional method indicates that C-dots act as a spectral sensitizer in hybrid C dots/g-C3N4 for water splitting. Our results offer new theoretical insights into this metal-free photocatalyst for water splitting. PMID- 26538202 TI - Size reduction of 3D-polymer-coated single-walled carbon nanotubes by ultracentrifugation. AB - We describe a novel single-walled carbon nanotube (SWNT) cutting method without introducing any structural defects on the tubes; namely, the finding that simple ultracentrifugation at 600 000g for the SWNTs coated with a cross-linked polymer formed by poly(N-isopropylacrylamide) (PNIPAM) or the polyethylene glycol carrying PNIPAM copolymer provides shortened (<200 nm) SWNTs, which was revealed by dynamic light scattering (DLS) and atomic force microscopy (AFM) measurements. The Raman and absorption measurements of the obtained SWNTs indicated that the graphitic structure and optical properties, such as characteristic absorption and photoluminescence in the near-IR region of the SWNTs, were almost unchanged even after the cutting. The obtained shortened SWNTs were individually solubilized in water and buffer solution due to the remaining cross-linked polymer structures on the SWNTs. The present method is very simple (only ultracentrifugation) and the yield is very high, which are the advantages in the preparation of many shortened isolated SWNTs with specific properties and functions that are applicable in many fields including bioapplications in vivo, such as imaging, NIR-hyperthermic treatment, photodynamic therapy, etc. PMID- 26538203 TI - Site Isolation Leads to Stable Photocatalytic Reduction of CO2 over a Rhenium Based Catalyst. AB - A porous organic polymer incorporating [(alpha-diimine)Re(CO)3Cl] moieties was produced and tested in the photocatalytic reduction of CO2, with NEt3 as a sacrificial donor. The catalyst generated both H2 and CO, although the Re moiety was not required for H2 generation. After an induction period, the Re-containing porous organic polymer produced CO at a stable rate, unless soluble [(bpy)Re(CO)3Cl] (bpy=2,2'-bipyridine) was added. This provides the strongest evidence to date that [(alpha-diimine)Re(CO)3Cl] catalysts for photocatalytic CO2 reduction decompose through a bimetallic pathway. PMID- 26538204 TI - Optimizing Anti-TNF-alpha Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases. AB - BACKGROUND & AIMS: It is not clear what serum levels of anti-tumor necrosis factor are associated with reduced intestinal inflammation in patients with inflammatory bowel disease (IBD). We aimed to identify serum levels of infliximab and adalimumab associated with mucosal healing in patients with IBD and to evaluate the putative gain in control of inflammation by incremental increases in drug levels. METHODS: We performed a retrospective cross-sectional study of 145 patients with IBD treated with infliximab (n = 78) or adalimumab (n = 67) at a medical center in Israel from 2009 through 2014. We collected data from colonoscopy examinations; mucosal healing was defined as simple endoscopic score of <3 or a Mayo score <=1. These data were compared with serum levels of anti tumor necrosis factor agents, clinical scores, and levels of C-reactive protein. RESULTS: Median serum levels of infliximab and adalimumab were significantly higher in patients with mucosal healing than patients with active disease (based on endoscopy) (for infliximab, 4.3 vs 1.7 MUg/mL, P = .0002; for adalimumab, 6.2 vs 3.1 MUg/mL, P = .01). Levels of infliximab above 5 MUg/mL (area under the curve = 0.75; P < .0001) and levels of adalimumab above 7.1 MUg/mL (area under the curve = 0.7; P = .004) identified patients with mucosal healing with 85% specificity. Increasing levels of infliximab beyond 8 MUg/mL produced only minimal increases in the rate of mucosal healing, whereas the association between higher level of adalimumab and increased rate of mucosal healing reached a plateau at 12 MUg/mL. In patients with measurable levels of infliximab >3 MUg/mL, the presence of antibodies to infliximab was associated with a lower rate of mucosal healing compared with patients with similar drug level without antibodies (16% vs 50%, respectively; P = .003). CONCLUSIONS: In a retrospective study, we found significant association between serum levels of anti-tumor necrosis factor agents and level of mucosal healing. We propose that serum levels of 6-10 MUg/mL for infliximab and 8-12 MUg/mL for adalimumab are required to achieve mucosal healing in 80%-90% of patients with IBD, and that this could be considered as a "therapeutic window." Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing. PMID- 26538205 TI - Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug Induced Small Bowel Injury: A Randomized, Placebo-Controlled Trial. AB - BACKGROUND & AIMS: Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti inflammatory drugs and PPIs simultaneously. We performed a randomized, double blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury. METHODS: Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2 inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 + placebo group, n = 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 + PPI group, n = 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination. RESULTS: A significantly higher proportion of subjects in the COX-2 + PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2 + placebo group (5 of 30 subjects; 16.7%; P = .04). Subjects in the COX-2 + PPI group had a significant increase in risk of small bowel injury compared with the COX-2 + placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2 + PPI group was greater than in each member of the COX-2 + placebo group (P = .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2 + PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2 + placebo group (P = .003); no such trend was found in the ileum. CONCLUSIONS: In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug induced small bowel injury. UMIN clinical trial registry number: UMIN000008883. PMID- 26538206 TI - Procedure Delays and Time of Day Are Not Associated With Reductions in Quality of Screening Colonoscopies. AB - BACKGROUND & AIMS: There have been conflicting results from studies to determine whether factors unrelated to endoscopist skill, such as fatigue, affect the quality of screening colonoscopy. We studied the effects of human and system factors on screening colonoscopy withdrawal time and likelihood of detecting an adenoma in a large cohort of patients. METHODS: We performed a retrospective analysis of operation and quality improvement data in colonoscopies performed at single academic medical center from November 2012 through February 2014. We collected data from the Northwestern Medicine Enterprise Data Warehouse on endoscopy procedure reports, patient demographics, and pathology reports of all patients undergoing endoscopy. We identified all screening colonoscopies during the study period and determined whether an adenoma was identified in each screening colonoscopy procedure. Our study included data from 7004 screening colonoscopies of patients 50-75 years old performed by endoscopists who performed at least 100 screening colonoscopies during the study period (n = 18). RESULTS: Approximately 27% of procedures began on time; the median colonoscope insertion time was 5.9 minutes (interquartile range, 4.0-8.6). In multivariable logistic regression analysis adjusting for covariates and endoscopist-level clustering, adenoma detection was not associated with procedure delay (P = .48), hour of day (P = .40), or performing the second of 2 colonoscopy blocks in 1 day (P = .88). Adenoma detection was associated with insertion time overall (P = .006), but there was no consistent directional relationship across insertion quintiles. CONCLUSIONS: Procedure delays and measured factors associated with fatigue, including time of day and multiple procedure blocks, do not reduce the odds of detecting an adenoma. Adenoma detection varies widely among providers, so efforts to improve adenoma detection should focus mainly on optimizing physician skill. PMID- 26538207 TI - Features and Progression of Potential Celiac Disease in Adults. AB - BACKGROUND & AIMS: Individuals with potential celiac disease have serologic and genetic markers of the disease with little or no damage to the small intestinal mucosa. We performed a prospective study to learn more about disease progression in these people. METHODS: We collected data from 77 adults (59 female; median age, 33 years) diagnosed with potential celiac disease (on the basis of serology and HLA type) at Bologna University in Italy from 2004 through 2013. The subjects had normal or slight inflammation of the small intestinal mucosa. Clinical, laboratory, and histologic parameters were evaluated at diagnosis and during a 3 year follow-up period. RESULTS: Sixty-one patients (46 female; median age, 36 years) showed intestinal and extraintestinal symptoms, whereas the remaining 16 (13 female; median age, 21 years) were completely asymptomatic at diagnosis. All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1. A higher proportion of symptomatic patients had autoimmune disorders (36%) and antinuclear antibodies (41%) than asymptomatic patients (5% and 12.5%, respectively), and symptomatic patients were of older age at diagnosis (P < .05). Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable. CONCLUSIONS: In a 3-year study of adults with potential celiac disease, we found most to have symptoms, but these improved on gluten withdrawal. Conversely, we do not recommend a gluten-free diet for asymptomatic adults with potential celiac disease because they do not tend to develop villous atrophy. PMID- 26538208 TI - Efficacy of Mirtazapine in Patients With Functional Dyspepsia and Weight Loss. AB - BACKGROUND & AIMS: A subset of patients with functional dyspepsia (FD) present with early satiation and weight loss, for which there are no established therapeutic options. We investigated the efficacy of mirtazapine (an antidepressant and antagonist of the histamine receptor H1, the alpha2 adrenergic receptor, and the serotonin receptors 5-HT2C and 5-HT-3) in patients with FD and weight loss. METHODS: We conducted a randomized, placebo-controlled pilot trial that studied 34 patients with FD (29 women; mean age, 35.9 +/- 2.3 years) with weight loss >10% of original body weight (mean loss, 12.4 +/- 2.3 kg) without depression or anxiety. After a run-in period, patients were randomly assigned to groups given placebo (n = 17) or mirtazapine 15 mg each day for 8 weeks (n = 17) in a double-blind manner. Subjects were evaluated during a 2-week baseline and 8 week treatment for dyspepsia symptom severity, quality of life (on the basis of the Nepean Dyspepsia Index), and gastrointestinal-specific anxiety; they were given a nutrient challenge test and weighed. Data were analyzed by using linear mixed models, followed by planned contrasts with adaptive step-down Bonferroni multiple testing correction. RESULTS: Two patients in each group dropped out. At weeks 4 and 8, mirtazapine significantly reduced mean dyspepsia symptom severity scores compared with week 0 (P = .003 and P = .017, respectively); there was no significant reduction in the placebo group (P > .37 for weeks 4 and 8). The difference in change from week 0 between mirtazapine and placebo showed a trend with a large effect size at week 4 (P = .059) that was not significant at week 8 (P = .55). However, improvements from week 0 to weeks 4 and 8 were significantly larger in the mirtazapine group than placebo group for early satiation, quality of life, gastrointestinal-specific anxiety, weight, and nutrient tolerance (mostly with large effect sizes). CONCLUSIONS: In a randomized, placebo controlled trial, mirtazapine significantly improved early satiation, quality of life, gastrointestinal-specific anxiety, nutrient tolerance, and weight loss in patients with FD. ClinicalTrials.gov number: NCT01240096. PMID- 26538210 TI - Comparisons of Caenorhabditis Fucosyltransferase Mutants Reveal a Multiplicity of Isomeric N-Glycan Structures. AB - Recent studies have shown a remarkable degree of plasticity in the N-glycome of the model nematode Caenorhabditis elegans; ablation of glycosylation-relevant genes can result in radically altered N-glycan profiles despite only minor biological phenotypic effects. Up to four fucose residues and five different linkages of fucose are known on the N-glycans of C. elegans. Due to the complexity in the wild type, we established three mutant strains defective in two core fucosyltransferases each (fut-1;fut-6, fut-1;fut-8, and fut-6;fut-8). Enzymatically released N-glycans were subject to HPLC and MALDI-TOF MS/MS, in combination with various treatments, to verify structural details. The N-glycome of the fut-1;fut-6 mutant was the most complex of the three double-mutant strains due to the extension of the core alpha1,6-fucose as well as the presence of fucose on the bisecting galactose. In contrast, maximally two fucoses were found on N-glycans of the fut-1;fut-8 and fut-6;fut-8 strains. The different locations and capping of fucose meant that up to 13 isomeric structures, many highly galactosylated, were determined for some single masses. These data not only show the high variability of the N-glycomic capacity of a "simple" nematode but also exemplify the need for multiple approaches to reveal individual glycan structures within complex invertebrate glycomes. PMID- 26538211 TI - Catheter Ablation of Pediatric Focal Atrial Tachycardia: Ten-Year Experience Using Modern Mapping Systems. AB - Experience of catheter ablation of pediatric focal atrial tachycardia (FAT) is still limited. There are data which were gathered prior to the introduction of modern 3D mapping and navigation systems into the clinical routine. Accordingly, procedures were associated with significant fluoroscopy and low success rates. The aim of this study was to present clinical and electrophysiological details of catheter ablation of pediatric FAT using modern mapping systems. Since March 2003, 17 consecutive patients <20 years underwent electrophysiological study (EPS) for FAT using the NavX((r)) system (n = 7), the non-contact mapping system (n = 6) or the LocaLisa((r)) system (n = 4), respectively. Radiofrequency was the primary energy source; cryoablation was performed in selected patients with a focus close to the AV node. In 16 patients, a total number of 19 atrial foci (right-sided n = 13, left-sided n = 6) could be targeted. In the remaining patient, FAT was not present/inducible during EPS. On an intention-to-treat basis, acute success was achieved in 14/16 patients (87.5 %) with a median number of 11 (1-31) energy applications. Ablation was unsuccessful in two patients due to an epicardial location of a right atrial focus (n = 1) and a focus close to the His bundle (n = 1), respectively. Median procedure time was 210 (84-332) min, and median fluoroscopy time was 13.1 (4.5-22.5) min. In pediatric patients with FAT, 3D mapping and catheter ablation provided improved clinical quality of care. Catheter ablation may be considered early in the course of treatment of this tachyarrhythmia in symptomatic patients. PMID- 26538209 TI - Morusin suppresses breast cancer cell growth in vitro and in vivo through C/EBPbeta and PPARgamma mediated lipoapoptosis. AB - BACKGROUND: Breast cancer is the most fatal malignant cancer among women, the conventional therapeutic modalities of it are limited. Morusin possesses cytotoxicity against some cancer cells in vitro. The purpose of this study is to test the growth inhibition effect of morusin on human breast cancer growth in vitro and in vivo and to explore the potential mechanism of its action. METHODS: The growth inhibition effect of morusin on human breast cancer cells in vitro and in vivo were tested by cell cytotoxicity, colony formation inhibition, adipogenic differentiation, apoptosis induction, and tumor growth inhibition in vivo assays. The potential molecular mechanisms underlying the growth inhibition effect of morusin on human breast cancer cells in vitro and in vivo were investigated with Western blotting evaluation of expression levels of transcription factors, C/EBPbeta and PPARgamma, adipogenic and apoptotic proteins in morusin treated breast cancer cells and tumor tissues. RESULTS: Morusin inhibited breast cancer cells growth in vitro and in vivo; it induced adipogenic differentiation, apoptosis and lipoapoptosis of cancer cells. CONCLUSIONS: Morusin has the potential to inhibit human breast cancer cell growth in vitro and in vivo through C/EBPbeta and PPARgamma mediated lipoapoptosis. PMID- 26538212 TI - Extended Application of the Hybrid Procedure in Neonates with Left-Sided Obstructive Lesions in an Evolving Cardiac Program. AB - The hybrid approach to management of hypoplastic left heart syndrome (HLHS) was developed as an alternative to neonatal Norwood surgery, providing a less invasive initial palliation for HLHS. We describe our experience in extending the concept of the hybrid procedure to palliate neonates with anatomically compromised systemic arterial blood flow in a variety of congenital cardiac anomalies and supporting its application as first-line palliation in centers developing their HLHS programs. Retrospective review of patients undergoing therapy for HLHS at a single institution from June 2008 to December 2014 was performed. Subject demographics, clinical and procedural data, along with follow up, were collected. Thirteen patients had initial hybrid palliation for HLHS during the time frame indicated at a median age of 8 days (range 1-29 days) and median weight of 3.4 kg (range 2.4-4.6 kg). Diagnoses included typical HLHS (n = 6), right-dominant unbalanced atrioventricular septal defect with arch hypoplasia (n = 4), double outlet right ventricle [subpulmonic VSD (n = 1) and intact ventricular septum (n = 1)] with hypoplastic transverse aortic arch and borderline left ventricular dimensions. Standard approach with bilateral pulmonary artery banding and ductal stenting was carried out in all thirteen patients. Two patients required two ductal stents at the time of index procedure. There were no intraprocedural complications. Median intubation length post procedure was 4 days (range 1-74 days). Median hospital stay post-procedure was 47 days (range 15-270 days). The overall mortality rate on follow-up through comprehensive stage 2 over the 6-year experience was 38 % (5 out of 13). Of note, the mortality rate was significantly lower in the latter 3 years of the study period when the procedure was adopted as a primary palliation for HLHS (14 % or 1 out of 7) compared to the initial 3-year period when it was reserved for higher risk cohorts (67 % or 4 out of 6). Median time to subsequent surgery was 3 months (range 1-4 months). One patient required further ductal stenting on follow-up and developed subsequently airway compression. On median follow-up of 24 months, two patients required pulmonary artery arterioplasty. The hybrid procedure may be used for palliation for a variety of cardiac lesions to avoid high-risk surgery in the neonatal period. This approach may be also an alternative in centers performing lower number of Norwood surgery, which has been associated with higher mortality. PMID- 26538213 TI - Event-Related Household Discussions Following the Boston Marathon Bombing and Associated Posttraumatic Stress Among Area Youth. AB - Despite research documenting the scope of disaster-related posttraumatic stress (PTS) in youth, less is known about how family processes immediately postdisaster might associate with child outcomes. The 2013 Boston Marathon bombing affords a unique opportunity to assess links between immediate family discussions about community trauma and child mental health outcomes. The present study examined associations between attack-related household discussions and child PTS among Boston-area youth ages 4 to 19 following the Marathon bombing (N = 460). Caregivers completed surveys 2 to 6 months postattack about immediate household discussions about the events, child exposure to potentially traumatic attack related experiences, and child PTS. During the Marathon bombing and manhunt, there was considerable heterogeneity in household discussions across area families, and several discussion items were differentially predictive of variability in children's PTS. Specifically, after controlling for children's direct exposure to the potentially traumatic attack/manhunt events, children showed lower PTS when it was their caregivers who informed them about the attack and manhunt, and when their caregivers expressed confidence in their safety and discussed their own feelings about the manhunt with their child. Children showed higher PTS when their caregivers did not discuss the events in front of them, asked others to avoid discussing the events in front of them, and expressed concern at the time that their child might not be safe. Child age and traumatic attack/manhunt exposure moderated several links between household discussions and child PTS. Findings underscore the importance of family communication and caregiver modeling during times of community threat and uncertainty. PMID- 26538214 TI - Formation of hollow and mesoporous structures in single-crystalline microcrystals of metal-organic frameworks via double-solvent mediated overgrowth. AB - The creation of hierarchical porosity in metal-organic frameworks (MOFs) could benefit various applications of MOFs such as gas storage and separation. Having single-crystalline microcrystals instead of poly-crystalline composites is critical for these potential applications of MOFs with hierarchical porosity. We developed a room temperature synthetic method to generate uniform hollow and mesoporous zeolitic imidazolate framework-8 (ZIF-8) microcrystals with a single crystalline structure via overgrowing a ZIF-8 shell in methanol solution on a ZIF 8 core with water adsorbed in the pores. The cavities formed as a result of the different solvent micro-environment. This double-solvent mediated overgrowth method could be applied to prepare other MOFs with hierarchical porosity. PMID- 26538216 TI - Visual Function Assessment in Medical Imaging Research. AB - BACKGROUND: Medical image perception research relies on visual data to study the diagnostic relationship between observers and medical images. A consistent method to assess visual function for participants in medical imaging research has not been developed and represents a significant gap in existing research. METHODS: Three visual assessment factors appropriate to observer studies were identified: visual acuity, contrast sensitivity, and stereopsis. A test was designed for each, and 30 radiography observers (mean age 31.6 years) participated in each test. RESULTS: Mean binocular visual acuity for distance was 20/14 for all observers. The difference between observers who did and did not use corrective lenses was not statistically significant (P = .12). All subjects had a normal value for near visual acuity and stereoacuity. Contrast sensitivity was better than population norms. CONCLUSION: All observers had normal visual function and could participate in medical imaging visual analysis studies. Protocols of evaluation and populations norms are provided. Further studies are necessary to understand fully the relationship between visual performance on tests and diagnostic accuracy in practice. PMID- 26538217 TI - Microbial Safety Assessment of a Double Check-Valve Patient Line in a Multiuse Contrast Delivery System. AB - PURPOSE: To demonstrate the microbial safety of a secure filling and injection kit designed to allow for multiple injections of contrast media from a single large-volume container in computed tomography (CT) and magnetic resonance (MR) imaging examinations. METHODS: Two male Papio anubis baboons were injected with technetium-99 labeled albumin to mimic a contaminated patient. Researchers injected iodinated contrast medium into the animals using an automated power injector via an antecubital vein, with an injection line fitted with a double check-valve positioned at a 45 degrees angle toward the vein (worst-case condition). Two contact times (before and after injection) were assessed in 3 experiments and repeated 3 times for a total of 9 tested lines. Radioactivity levels were measured in the animals' plasma and in the injection system. RESULTS: Crude values were corrected for background signal and technetium Tc 99m radioactive decay. Results showed an absence of contamination in the line above the check-valve. Negative results were because the mean value of background noise was similar to the crude values measured. DISCUSSION: Injecting contrast media from a large-volume container decreases the cost of CT and MR examinations. However, this practice, which involves the use of the same injection system for multiple patients, is associated with a risk of cross-contamination and requires manufacturers to demonstrate the safety of reusable injection kits. CONCLUSION: Based on appropriate demonstration of worst-case conditions and the use of a radiolabeled molecule mimicking a pathogen particle (ie, as small as viral particles), this study highlights the safety and performance of the tested injection system to perform repeated injections from a multidose container to more than one patient, regardless of the conditions and duration of the examination. PMID- 26538215 TI - A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression. AB - BACKGROUND: Aberrant expression of A20 has been reported in several human malignancies including hepatocellular carcinoma (HCC). However, its clinical relevance and potential role in HCC remain unknown. METHODS: Quantitative PCR, Western blots and immunohistochemistry analyses were used to quantify A20 expression in HCC samples and cell lines. The correlation of A20 expression with clinicopathologic features was analyzed in a cohort containing 143 patients with primary HCC. Kaplan-Meier curves were used to evaluate the association between A20 expression and patient survival. Functional studies were performed to determine the effects of A20 on proliferation and metastasis of HCC cells in vitro and in vivo. RESULTS: Expression of A20 was increased in HCC tissues and cell lines. Increased expression of A20 was negatively correlated with the tumor size, TNM stage, tumor thrombus formation, capsular invasion and serum AFP levels. Patients with higher A20 expression had a prolonged disease-free survival and overall survival than those with lower A20 expression. Forced expression of A20 significantly inhibited the proliferative and invasive properties of HCC cells both in vitro and in vivo, whereas knockdown of A20 expression showed the opposite effects. Further studies revealed that expression of A20 was inversely correlated with Twist1 levels and NF-kappaB activity in HCC tissues and cell lines. A20-induced suppression of proliferation and migration of HCC cells were mainly mediated through inhibition of Twist1 expression that was regulated at least partly by A20-induced attenuation of NF-kappaB activity. CONCLUSIONS: Our results demonstrate that A20 plays a negative role in the development and progression of HCC probably through inhibiting Twist1 expression. A20 may serve as a novel prognostic biomarker and potential therapeutic target for HCC patients. PMID- 26538218 TI - Evaluation of Stress and a Stress-Reduction Program Among Radiologic Technologists. AB - PURPOSE: To investigate stress levels and causes of stress among radiologic technologists and determine whether an intervention could reduce stress in a selected radiologic technologist population. METHODS: Demographic characteristics and data on preintervention stress sources and levels were collected through Internet-based questionnaires. A 6-week, self-administered, mindfulness-based stress-reduction program was conducted as a pilot intervention with 42 radiologic technologists from the Veterans Administration Medical Center. Data also were collected postintervention. Identified sources of stress were compared with findings from previous studies. RESULTS: Some radiologic technologists experienced improvement in their perceptions of stress after the intervention. Sources of stress for radiologic technologists were similar to those shown in earlier research, including inconsistent management, poor management communication, conflicting demands, long work hours, excessive workloads, lack of work breaks, and time pressures. CONCLUSION: The mindfulness-based stress reduction program is an example of an inexpensive method that could improve personal well-being, reduce work errors, improve relationships in the workplace, and increase job satisfaction. More research is needed to determine the best type of intervention for stress reduction in a larger radiologic technologist population. PMID- 26538219 TI - Medical Ethics and Law in Radiologic Technology. AB - At every stage of their careers, radiologic technologists and student technologists must adhere to high ethical standards, obey the law, and consistently conduct themselves with professionalism. This article explains how modern health care ethics evolved, focusing on 8 important theorists. It also describes the ethical responsibilities of health care providers and the rights of patients. Important civil rights laws are discussed, focusing on the rights of health care workers as employees. A brief overview of the U.S. legal system follows, including the causes of action that most commonly involve health care professionals. Finally, this article discusses professionalism and its implications for radiologic technologists. PMID- 26538220 TI - Medical Imaging of Oral and Oropharyngeal Cancer. AB - Oral cancer is associated with documented risk factors, yet no comprehensive screening program is in place in the United States for early detection of the disease. Oral cancer often is diagnosed in more advanced stages, resulting in a poor prognosis. Dental practitioners and radiographers play an important role in the management of the disease and in helping to improve the quality of life for people who have oral cancer. This article discusses types of oral and oropharyngeal cancer, their diagnosis, treatment options, and the role of dental imaging in patients with these cancers. PMID- 26538221 TI - Leslie Winter on Her Role and the Challenges Facing Our Profession. PMID- 26538222 TI - Computed Tomography for Assessment of Coronary Artery Bypass Grafts. PMID- 26538223 TI - Microexpressions: Do They Have Value in Radiology? PMID- 26538224 TI - E-Portfolios for Radiologic Technology Students. PMID- 26538225 TI - Developing Clinical Competence in Diagnostic Imaging Students. PMID- 26538226 TI - Writing Research Proposals. PMID- 26538227 TI - Image Fusion. PMID- 26538228 TI - CT-guided Intra-abdominal Abscess Drainage. AB - Intra-abdominal abscesses arise from complications of surgery and disease. Computed tomography (CT) facilitates abscess drainage procedures while reducing the risks and costs associated with surgery. These procedures require collaboration to ensure positive patient outcomes. To perform their role in CT guided intra-abdominal abscess drainage, radiologic technologists must understand patient care, instrumentation, imaging techniques, and underlying disease processes specific to the anatomical site. Once these considerations are grasped, CT technologists can help radiologists and administrators to determine cost effective instrumentation and quality control specific to the patient and institution. PMID- 26538229 TI - From Student to Professional: A Personal Perspective on Lifelong Learning. PMID- 26538230 TI - Sequence-Defined Peptidocopolymers: The Effect of Small Molecular Linkers. AB - In this paper, the contribution of nonpeptido small molecular linkers to the properties of sequence-defined peptidocopolymers was investigated. We synthesized four novel bioinspired peptidocopolymers (P1-P4) based on elastin motif pentapeptide (Gly-Pro-Gly-Gly-Ala) by step growth polymerization. Small molecular linkers, including tetraethylene glycol (M1), adipic acid (M2), isophthalic acid (M3), and terephthalic acid (M4) with different length and flexibility are employed to tune the conformation, physical, and mechanical properties of the corresponding peptidocopolymers P1-P4 respectively. Raman spectroscopy, solid state NMR, and circular dichroism spectroscopy were used to characterize the conformation of the four peptidocopolymers. The experimental results were further confirmed by molecular dynamics simulation of typical P2 and P4 with different repeating units. High ratio of beta-turn conformation was observed in P2 due to flexible linker M2; while affected by the hydrophobic and rigid M4 linker, P4 retained less beta-turn conformation and showed drastic difference on macroscopic properties. These simple step growth synthesis techniques provide an efficient approach toward a broad range of bioinspired peptidocopolymers, which takes a further insight into the significant effect of nonpeptido linkages toward chemical-synthesized peptidocopolymers. PMID- 26538231 TI - Shift in performance of food safety management systems in supply chains: case of green bean chain in Kenya versus hot pepper chain in Uganda. AB - BACKGROUND: This study investigates the level of design and operation of food safety management systems (FSMS) of farmers and export traders in Kenya and Uganda. FSMS diagnostic tools developed for the fresh produce chain were used to assess the levels of context riskiness, FSMS activities and system output in primary production (n = 60) and trade (n = 60). High-risk context characteristics combined with basic FSMS are expected to increase the risk on unsafe produce. RESULTS: In Uganda both farmers and export traders of hot peppers operate in a high- to moderate-risk context but have basic FSMS and low systems output. In Kenya, both farmers and export traders of green beans operate in a low- to moderate-risk context. The farmers have average performing FSMS, whereas export trade companies showed more advanced FSMS and system output scores ranging from satisfactory to good. CONCLUSION: Large retailers supplying the EU premium market play a crucial role in demanding compliance with strict voluntary food safety standards, which was reflected in the more advanced FSMS and good system output in Kenya, especially traders. In Kenya, a clear shift in more fit-for-purpose FSMS and higher system output was noticed between farms and trade companies. In the case of Uganda, traders commonly supply to the less demanding EU wholesale markets such as ethnic specialty shops. They only have to comply with the legal phytosanitary and pesticide residue requirements for export activities, which apparently resulted in basic FSMS and low system output present with both farmers and traders. (c) 2015 Society of Chemical Industry. PMID- 26538232 TI - Early View of the Effectiveness of New Direct-Acting Antiviral (DAA) Regimens in Patients with Hepatitis C Virus (HCV). AB - INTRODUCTION: Clinical trials have demonstrated the efficacy of all-oral direct acting antiviral (DAA) regimens in the treatment of patients infected with hepatitis C virus (HCV). This study assessed real-world effectiveness of two recently approved regimens; paritaprevir/ritonavir/ombitasvir; dasabuvir (3D), and sofosbuvir/ledipasvir (SOF/LDV) in patients with HCV genotype 1. METHODS: A retrospective analysis of administrative claims data (IMS Health Patient-Centric Data Warehouse/Medivo database) from October 1, 2013 to August 14, 2015 was conducted. Patients >=19 years of age with a HCV genotype 1 infection, a prescription fill for 3D or SOF/LDV, and >=1 HCV viral load (VL) assessment from weeks 4-30 post-treatment were selected for analysis. Percentages of patients achieving sustained virologic response (SVR; defined as HCV RNA <=43 IU/mL) were determined. Unadjusted SVR rates were compared between treatment groups using Fisher's exact tests. SVR rates were also assessed using multivariate regression with adjustment for age group, sex, and treatment history. Analyses were repeated for a subset of patients with VL assessment from 12 to 30 weeks post-treatment. RESULTS: A total of 1707 (44 3D and 1663 SOF/LDV) patients were included. The majority (60%) were male, 49% were aged 55-64 years, and 97% were treatment-naive 1 year prior to index. The unadjusted relative risk (RR) for achieving SVR in patients treated with SOF/LDV compared with 3D was 0.98%, 95% confidence interval (CI): 0.93-1.02. After adjusting for the baseline covariates, the RR was 0.98%, 95% CI: 0.94-1.03. CONCLUSIONS: In this early view of real-world data, effectiveness of all-oral DAA regimens in HCV genotype 1 patients was concordant with results from registration trials. SVR rates were similar for the two regimens. Further studies are needed to confirm these results. FUNDING: AbbVie, Inc. PMID- 26538234 TI - Prediction of virologic response to tenofovir mono-rescue therapy for multidrug resistant chronic hepatitis B. AB - Most guidelines suggest combination therapy including nucleoside and nucleotide analogues for the treatment of chronic hepatitis B (CHB) with multidrug resistance (MD-R). However, long-term combination treatment can evoke high costs and safety problems. Therefore, we investigated the efficacy of tenofovir disoproxil fumarate (TDF) mono-rescue therapy for viral suppression in patients with CHB exhibiting MD-R. We reviewed patients with CHB exhibiting antiviral drug resistance treated by TDF mono-rescue therapy from December 2012 to June 2014. The patients were categorized into three groups: lamivudine-resistance (LAM-R) group (n = 290), and LAM-R + adefovir-resistance (ADV-R) group (n = 43), and LAM R + entecavir-resistance (ETV-R) group (n = 113). We compared the virologic response rate according to the multiplicity of resistance and investigated the predictive factors of a virologic response. For a median of 15 months (range, 6 24 months) of TDF mono-rescue therapy, the cumulative virologic response rates were 82.8, 81.4, and 84.1% in the LAM-R, LAM-R + ADV-R, and LAM-R + ETV-R groups, respectively (P = 0.239). Multivariate analysis revealed that multiplicity of resistance did not influence the achievement of a virologic response (P = 0.218). However, the baseline HBV DNA level significantly influenced the achievement of a virologic response for the treatment of CHB with MD-R (P < 0.001). TDF mono rescue therapy is an appropriate treatment for CHB with MD-R, and the baseline HBV DNA level is a significant predictive factor for a virologic response. These factors should be considered before treating CHB with MD-R. PMID- 26538233 TI - Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. AB - HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family. PMID- 26538235 TI - Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits. AB - Despite significant clinical interest in renal denervation as a therapy, the role of the renal nerves in the physiological regulation of renal blood flow (RBF) remains debated. We hypothesized that the renal nerves physiologically regulate beat-to-beat RBF variability (RBFV). This was tested in chronically instrumented, healthy rabbits that underwent either bilateral surgical renal denervation (DDNx) or a sham denervation procedure (INV). Artifact-free segments of RBF and arterial pressure (AP) from calmly resting, conscious rabbits were used to extract RBFV and AP variability for time-domain, frequency-domain, and nonlinear analysis. Whereas steady-state measures of RBF, AP, and heart rate did not statistically differ between groups, DDNx rabbits had greater RBFV than INV rabbits. AP-RBF transfer function analysis showed greater admittance gain in DDNx rabbits than in INV rabbits, particularly in the low-frequency (LF) range where systemic sympathetic vasomotion gives rise to AP oscillations. In the LF range, INV rabbits exhibited a negative AP-RBF phase shift and low coherence, consistent with the presence of an active control system. Neither of these features were present in the LF range of DDNx rabbits, which showed no phase shift and high coherence, consistent with a passive, Ohm's law pressure-flow relationship. Renal denervation did not significantly affect nonlinear RBFV measures of chaos, self affinity, or complexity, nor did it significantly affect glomerular filtration rate or extracellular fluid volume. Cumulatively, these data suggest that the renal nerves mediate LF renal sympathetic vasomotion, which buffers RBF from LF AP oscillations in conscious, healthy rabbits. PMID- 26538236 TI - ZnT4 (SLC30A4)-null ("lethal milk") mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation. AB - During lactation, highly specialized secretory mammary epithelial cells (MECs) produce and secrete huge quantities of nutrients and nonnutritive factors into breast milk. The zinc (Zn) transporter ZnT4 (SLC30A4) transports Zn into the trans-Golgi apparatus for lactose synthesis, and across the apical cell membrane for efflux from MECs into milk. This is consistent with observations in "lethal milk" (lm/lm) mice, which have a truncation mutation in SLC30A4, and present with not only low milk Zn concentration, but also smaller mammary glands, decreased milk volume, and lactation failure by lactation day 2. However, the molecular underpinnings of these defects are not understood. Here, we used lactating C57BL/6J(lm/lm) (ZnT4-null) mice to explore the consequences of a ZnT4-null phenotype on mammary gland function during early lactation. Lactating C57BL/6J(lm/lm) mice had significantly fewer, smaller, and collapsed alveoli comprising swollen, lipid-filled MECs during early lactation. These defects were associated with decreased Akt expression and STAT5 activation, indicative of defects in MEC secretion. In addition, increased expression of ZnT2, TNF-alpha, and cleaved e-cadherin concomitant with increased activation of STAT3 implicated the loss of ZnT4 in precocious activation of involution. Collectively, our study indicates that the loss of ZnT4 has profound consequences on MEC secretion and may promote tissue remodeling in the mammary gland during early lactation. PMID- 26538237 TI - Adipogenic role of alternatively activated macrophages in beta-adrenergic remodeling of white adipose tissue. AB - De novo brown adipogenesis involves the proliferation and differentiation of progenitors, yet the mechanisms that guide these events in vivo are poorly understood. We previously demonstrated that treatment with a beta3-adrenergic receptor (ADRB3) agonist triggers brown/beige adipogenesis in gonadal white adipose tissue following adipocyte death and clearance by tissue macrophages. The close physical relationship between adipocyte progenitors and tissue macrophages suggested that the macrophages that clear dying adipocytes might generate proadipogenic factors. Flow cytometric analysis of macrophages from mice treated with CL 316,243 identified a subpopulation that contained elevated lipid and expressed CD44. Lipidomic analysis of fluorescence-activated cell sorting isolated macrophages demonstrated that CD44+ macrophages contained four- to five fold higher levels of the endogenous peroxisome-proliferator activated receptor gamma (PPARgamma) ligands 9-hydroxyoctadecadienoic acid (HODE), and 13-HODE compared with CD44- macrophages. Gene expression profiling and immunohistochemistry demonstrated that ADRB3 agonist treatment upregulated expression of ALOX15, the lipoxygenase responsible for generating 9-HODE and 13 HODE. Using an in vitro model of adipocyte efferocytosis, we found that IL-4 primed tissue macrophages accumulated lipid from dying fat cells and upregulated expression of Alox15. Furthermore, treatment of differentiating adipocytes with 9 HODE and 13-HODE potentiated brown/beige adipogenesis. Collectively, these data indicate that noninflammatory removal of adipocyte remnants and coordinated generation of PPARgamma ligands by M2 macrophages provides localized adipogenic signals to support de novo brown/beige adipogenesis. PMID- 26538239 TI - Water deprivation-partial rehydration induces sensitization of sodium appetite and alteration of hypothalamic transcripts. AB - iSodium intake occurs either as a spontaneous or induced behavior, which is enhanced, i.e., sensitized, by repeated episodes of water deprivation followed by subsequent partial rehydration (WD-PR). In the present work, we examined whether repeated WD-PR alters hypothalamic transcripts related to the brain renin angiotensin system (RAS) and apelin system in male normotensive Holtzman rats (HTZ). We also examined whether the sodium intake of a strain with genetically inherited high expression of the brain RAS, the spontaneously hypertensive rat (SHR), responds differently than HTZ to repeated WD-PR. We found that repeated WD PR, besides enhancing spontaneous and induced 0.3 M NaCl intake, increased the hypothalamic expression of angiotensinogen, aminopeptidase N, and apelin receptor transcripts (43%, 60%, and 159%, respectively) in HTZ at the end of the third WD PR. Repeated WD-PR did not change the daily spontaneous 0.3 M NaCl intake and barely changed the need-induced 0.3 M NaCl intake of SHR. The same treatment consistently enhanced spontaneous daily 0.3 M NaCl intake in the normotensive Wistar-Kyoto rats. The results show that repeated WD-PR produces alterations in hypothalamic transcripts and also sensitizes sodium appetite in HTZ. They suggest an association between the components of hypothalamic RAS and the apelin system, with neural and behavioral plasticity produced by repeated episodes of WD-PR in a normotensive strain. The results also indicate that the inherited hyperactive brain RAS is not a guarantee for sensitization of sodium intake in the male adult SHR exposed to repeated WD-PR. PMID- 26538240 TI - NIR-to-NIR Two-Photon Scanning Laser Microscopy Imaging of Single Nanoparticles Doped by Yb(III) Complexes. AB - The photophysical and nonlinear optical properties of water-soluble chromophore functionalised tris-dipicolinate complexes [LnL3](3-) (Ln=Yb and Nd) are thoroughly studied, revealing that only the Yb(III) luminescence can be sensitized by a two-photon excitation process. The stability of the complex in water is strongly enhanced by embedding in dispersible organosilicate nanoparticles (NPs). Finally, the spectroscopic properties of [NBu4]3 [YbL3] are studied in solution and in the solid state. The high brightness of the NPs allows imaging them as single objects using a modified two-photon microscopy setup in a NIR-to-NIR configuration. PMID- 26538241 TI - Common Factors and Depressive Symptom Relief Trajectories in Group Teletherapy for Persons Ageing with HIV. AB - : Telepsychology research has focused primarily on treatment efficacy, with far less attention devoted to how common factors relate to teletherapy outcomes. This research identified trajectories of depressive symptom relief in 105 older people living with HIV with elevated depressive symptoms enrolled in a randomized clinical trial testing two 12-session group teletherapies and compared common factors (e.g., therapeutic alliance and group cohesion) across depressive symptom trajectory groups. Growth mixture modelling of weekly depression scores identified three depressive symptom change groups: (1) 'early improvers' (31%) who reported reductions in depressive symptoms by Session 4; (2) 'delayed improvers' (16%) whose symptoms improved after Session 5 and (3) 'non-improvers' (53%). Therapeutic alliance was unrelated to treatment outcome group. Group cohesion was greater in early improvers than non-improvers. Group cohesion was unexpectedly lower, and group member similarity was greater in delayed improvers than non-improvers. Early improvers had been living with HIV/AIDS for fewer years than non-improvers. In group teletherapy, group cohesion and group member similarity are more important than client-therapist alliance. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: In group teletherapy with older people living with HIV (OPLWHIV), three latent outcome trajectory groups emerged over the 12-week treatment period: (1) non-improvers (53%); (2) early improvers (31%) and (3) delayed improvers (16%). In group teletherapy with OPLWHIV, group cohesion is a stronger predictor of depressive symptom relief than is client therapist alliance. OPLWHIV in group teletherapy who do not respond to treatment until the latter therapy sessions can still experience depressive symptom relief comparable with early responders. PMID- 26538242 TI - Profile of Patients Hospitalized through the Emergency Room to the Medicine Ward and their Short-term Outcome at a Tertiary Care Hospital in Delhi. AB - INTRODUCTION: With an increasing number of sicker patients, limited hospital beds, and an emphasis on day care, the profile of patients hospitalized to medicine wards has undergone a radical re-definition. The increasing share of patients hospitalized through the emergency department for acute care to medicine wards has left little space for hospitalization through the outpatient department (OPD). There are some global data available on the profile of patients presenting to the emergency rooms (ERs) and their subsequent outcome. Data from developing countries, especially India, in this regard are lacking. METHODS: This cross sectional study included all patients hospitalized to the medicine ward through the medical emergency services, provided by the Department of Medicine, each Wednesday and every sixth Sunday for the entire year (a total of 62 days), from November 2010 through October 2011, and followed their outcome up to seven days after hospitalization. RESULTS: Of the 3,618 cases presenting to medicine emergency on these days, 1,547 (42.3%) were advised admission. Nine hundred sixty seven reported to the medicine wards. One hundred eleven (7.73%) expired within 24 hours; others absconded, were lost in transit, did not consent to participation, or were discharged. During the next seven days, 452 (46.7%) recovered sufficiently and were discharged to go home. Two hundred thirty (23.8%) left the hospital without informing the medical staff. Fourteen (1.4%) patients were transferred to other departments. One hundred thirty-seven (8.8%) patients died during the next six days of hospitalization. After Multivariate Logistic Regression analysis, abnormal Glasgow Coma Scale (GCS) score, high systolic blood pressure (BP), age, increased total leucocyte count, increased globulin, low bicarbonate in arterial blood, low Mini Mental Status Examination (MMSE) score, and a raised urea >40 mg/dL were found to be associated significantly with mortality. CONCLUSION: Of the 1,547 patients who needed urgent hospitalization, 248 (16%) died within the first week, one-half of them within the first 24 hours. An advanced age, abnormal GCS score, low MMSE score, increased systolic BP, leukocytosis, acidosis, and uremia were found to be associated with a fatal outcome. Therefore, nearly one-half of the patients who would have a fatal short term outcome were likely to do so within the first 24 hours, making the first day of presentation "the golden day" period. PMID- 26538238 TI - Reactive oxygen species: players in the cardiovascular effects of testosterone. AB - Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID- 26538243 TI - A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons. AB - We studied schizophrenia liability in a Danish population-based sample of 44 twin pairs (13 MZ, 31 DZ, SS plus OS) in order to replicate previous twin study findings using contemporary diagnostic criteria, to examine genetic liability shared between schizophrenia and other disorders, and to explore whether variance in schizophrenia liability attributable to environmental factors may have decreased with successive cohorts exposed to improvements in public health. ICD 10 diagnoses were determined by clinical interview. Although the best-fitting, most parsimonious biometric model of schizophrenia liability specified variance attributable to additive genetic and non-shared environmental factors, this model did not differ significantly from a model that also included non-additive genetic factors, consistent with recent interview-based twin studies. Schizophrenia showed strong genetic links to other psychotic disorders but much less so for the broader category of psychiatric disorders in general. We also observed a marginally significant decline in schizophrenia variance attributable to environmental factors over successive Western European cohorts, consistent perhaps with improvements in diagnosis and in prenatal and perinatal care and with a secular decline in the prevalence of schizophrenia in that region. PMID- 26538245 TI - Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients. AB - Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P < 0.01). An unfavorable outcome was associated with low concentrations of voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. PMID- 26538244 TI - Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene? AB - Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G*E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G*E effects. In all three domains, G*E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE. PMID- 26538248 TI - Stories of South Asian clinical excellence: who won the 2015 BMJ Awards? PMID- 26538247 TI - Visceral adiposity is associated with altered myocardial glucose uptake measured by (18)FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes. AB - BACKGROUND: The heart requires constant sources of energy mostly from free fatty acids (FFA) and glucose. The alteration in myocardial substrate metabolism occurs in the heart of diabetic patients, but its specific association with other metabolic variables remains unclear. We aimed to evaluate glucose uptake in hearts of subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) using [(18)F]-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) in association with visceral and subcutaneous adiposity, and metabolic laboratory parameters. METHODS: A total of 346 individuals (NGT, n = 76; prediabetes, n = 208; T2DM, n = 62) in a health promotion center of a tertiary hospital were enrolled. The fasting myocardial glucose uptake, and visceral and subcutaneous fat areas were evaluated using (18)FDG-PET and abdominal computed tomography, respectively. RESULTS: Myocardial glucose uptake was significantly decreased in subjects with T2DM compared to the NGT or prediabetes groups (p for trend = 0.001). Multivariate linear regression analyses revealed that visceral fat area (beta = -0.22, p = 0.018), fasting FFA (beta = 0.39, p < 0.001), and uric acid levels (beta = -0.21, p = 0.007) were independent determinants of myocardial glucose uptake. Multiple logistic analyses demonstrated that decreased myocardial glucose uptake (OR 2.32; 95% CI 1.02-5.29, p = 0.045) and visceral fat area (OR 1.02, 95% CI 1.01-1.03, p = 0.018) were associated with T2DM. CONCLUSIONS: Our findings indicate visceral adiposity is strongly associated with the alteration of myocardial glucose uptake evaluated by (18)FDG-PET, and its association further relates to T2DM. PMID- 26538249 TI - A rare case of primary cardiac lymphoma. AB - A 71-year-old man presented with shortness of breath and tachycardia along with systemic symptoms of weight loss and lethargy. A pulmonary embolus was the initial suspected diagnosis but through extensive investigations a rarer cause of his symptoms was identified. This case demonstrates the importance of cardiac imaging in the assessment and non-invasive tissue characterisation of a suspected cardiac tumour; in our case, this was subsequently confirmed by careful histological/immunocytochemical evaluation of the pericardial effusion as a primary cardiac B-cell non-Hodgkin's lymphoma, thus enabling appropriate management leading to an excellent clinical outcome. PMID- 26538250 TI - Subaortic membrane mimicking hypertrophic cardiomyopathy. AB - A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. PMID- 26538251 TI - Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment. AB - The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-beta) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide. PMID- 26538252 TI - Primary cilia in energy balance signaling and metabolic disorder. AB - Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alstrom syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell's antenna to obesity and type II diabetes. PMID- 26538253 TI - Qualitative vs. quantitative atopic dermatitis criteria - in historical and present perspectives. AB - This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis (AD) based on the importance of atopic features - subjective, objective, and those derived from laboratory tests - the new partly promising AD biomarkers. 'Atopy', introduced in 1923, denoted 'the sense of a strange disease without a precise place in the body'. A decade later, Sulzberger and Hill, first defined 'atopic dermatitis'. The pioneering well-recognized criteria, 'Hanifin & Rajka' (Acta Derm Venereol, 92, 1980, 44), were developed empirically on 'clinical experience' and expert consensus. As opposed to the widely used, rather anamnestic 'UK Criteria' (1994), they have few formal validation studies, but appear to well embrace various atopic phenotypes. Pruritus, xerosis, typical morphology/distribution of dermatitis and tendency to a relapsing/chronic course are common basic features in AD criteria, whereas skin sensitivity, heredity and various ill-defined atopic stigmata also seem to comprise the atopic phenomenon. Specific pheno- and endotypes are now emerging potentially enabling us to better classify patients with AD, but the influence of these on the diagnosis of AD is so far unclear. Few diagnostic models use quantitative scoring systems to establish AD cases from normal population, which, however, may be useful to better study and manage this disease. Long-term prospective observational studies, from which few are available at this point, along with interventional studies, are a perquisite and will provide the best option to improve our understanding of its complex characteristics and etiology. PMID- 26538254 TI - Secondary metabolites produced by marine streptomyces as antibiofilm and quorum sensing inhibitor of uropathogen Proteus mirabilis. AB - Quorum-sensing regulates bacterial biofilm formation and virulence factors, thereby making it an interesting target for attenuating pathogens. In this study, we investigated anti-biofilm and anti-quorum-sensing compounds from secondary metabolites of halophiles marine streptomyces against urinary catheter biofilm forming Proteus mirabilis without effect on growth viability. A total of 40 actinomycetes were isolated from samples collected from different places in Iraq including marine sediments and soil samples. Fifteen isolates identified as streptomyces and their supernatant screened as anti-quorum-sensing by inhibiting quorum-sensing regulated prodigiosin biosynthesis of Serratia marcescens strain Smj-11 as a reporter strain. Isolate Sediment Lake Iraq (sdLi) showed potential anti-quorum-sensing activity. Out of 35 clinical isolates obtained from Urinary catheter used by patient at the Universiti Kebangsaan Malaysia Medical Center, 22 isolates were characterized and identified as Proteus mirabilis. Isolate Urinary Catheter B4 (UCB4) showed the highest biofilm formation with highest resistance to used antibiotic and was chosen for further studies. Ethyl acetate secondary metabolites extract was produced from sdLi isolate. First, we determined the Minimum Inhibitory Concentration (MIC) of sdLi crude extract against UCB4 isolate, and all further experiments used concentrations below the MIC. Tests of subinhibitory concentrations of sdLi crude extract showed good inhibition against UCB4 isolate biofilm formation on urinary catheter and cover glass using Scanning electron microscopy and light microscopy respectively. The influence of sub-MIC of sdLi crude extract was also found to attenuate the quorum sensing (QS) dependent factors such as hemolysin activity, urease activity, pH value, and motility of UCB4 isolate. Evidence is presented that these nontoxic secondary metabolites may act as antagonists of bacterial quorum sensing by competing with quorum-sensing signals for receptor binding. PMID- 26538255 TI - Study on the behavior of heavy metals during thermal treatment of municipal solid waste (MSW) components. AB - Laboratory experiments were conducted to investigate the volatilization behavior of heavy metals during pyrolysis and combustion of municipal solid waste (MSW) components at different heating rates and temperatures. The waste fractions comprised waste paper (Paper), disposable chopstick (DC), garbage bag (GB), PVC plastic (PVC), and waste tire (Tire). Generally, the release trend of heavy metals from all MSW fractions in rapid-heating combustion was superior to that in low-heating combustion. Due to the different characteristics of MSW fractions, the behavior of heavy metals varied. Cd exhibited higher volatility than the rest of heavy metals. For Paper, DC, and PVC, the vaporization of Cd can reach as high as 75% at 500 degrees C in the rapid-heating combustion due to violent combustion, whereas a gradual increase was observed for Tire and GB. Zn and Pb showed a moderate volatilization in rapid-heating combustion, but their volatilities were depressed in slow-heating combustion. During thermal treatment, the additives such as kaolin and calcium can react or adsorb Pb and Zn forming stable metal compounds, thus decreasing their volatilities. The formation of stable compounds can be strengthened in slow-heating combustion. The volatility of Cu was comparatively low in both high and slow-heating combustion partially due to the existence of Al, Si, or Fe in residuals. Generally, in the reducing atmosphere, the volatility of Cd, Pb, and Zn was accelerated for Paper, DC, GB, and Tire due to the formation of elemental metal vapor. TG analysis also showed the reduction of metal oxides by chars forming elemental metal vapor. Cu2S was the dominant Cu species in reducing atmosphere below 900 degrees C, which was responsible for the low volatility of Cu. The addition of PVC in wastes may enhance the release of heavy metals, while GB and Tire may play an opposite effect. In controlling heavy metal emission, aluminosilicate- and calcium-based sorbents can be co-treated with fuels. Moreover, pyrolysis can be a better choice for treatment of solid waster in terms of controlling heavy metals. PVC and Tire should be separated and treated individually due to high possibility of heavy metal emission. This information may then serve as a guideline for the design of the subsequent gas cleaning plant, necessary to reduce the final emissions to the atmosphere to an acceptable level. PMID- 26538256 TI - Sulfur crosslinks from thermal degradation of chitosan dithiocarbamate derivatives and thermodynamic study for sorption of copper and cadmium from aqueous system. AB - Pristine chitosan beads were modified with sulfur (S)-containing functional groups to produce thiolated chitosan beads (ETB), thereby increasing S donor ligands and crosslinks. The effect of temperature, heating time, carbon disulfide (CS2)/chitosan ratio, and pH on total S content of ETB was examined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The total S content of ETB increased with increasing CS2/chitosan ratio and decreased with decreasing pH and increasing temperature (>60 degrees C) and heating time (at 60 degrees C). Spectroscopic analyses revealed the presence of thiol (-SH)/thione, disulfide (-S-S-), and sulfonate groups in ETB. The thiolation mechanism involves decomposition of dithiocarbamate groups, thereby forming thiourea crosslinks and trithiocarbonate, resulting in -SH oxidation to produce -S-S- crosslinks. The partially formed ETB crosslinks contribute to its acid stability and are thermodynamically feasible in adsorbing Cd and Cu. The S-containing functional groups added to chitinous wastes act as sorbents for metal remediation from acidic environments. PMID- 26538257 TI - Addressing the role of earthworms in treating domestic wastewater by analyzing biofilm modification through chemical and spectroscopic methods. AB - Vermifiltration eco-friendly system is an alternative and low-cost artificial ecosystem for decentralized wastewater treatment and excess sludge reduction. The biofilm characteristics of a vermifilter (VF) with earthworms, Eisenia fetida, for domestic wastewater treatment were studied. A conventional biofilter (BF) without earthworms served as the control. Pore number in VF biofilm was significantly more than BF biofilm, and VF biofilm showed a better level administrative structure through scanning electron microscope. VF biofilms had lower levels of protein and polysaccharide, but phosphoric acids and humic acid showed the opposite results. Furthermore, in the presence of earthworms, VF biofilms contained higher total organic carbon (TOC) percentage composition in the condition of less volatile suspended substances (VSS) contents. Dehydrogenase activity (DHA) and adenosine triphosphate (ATP) contents along VF showed better results than BF by increment of 12.84 ~ 16.46 %. Overall findings indicated that the earthworms' presence remarkably decreases biofilm contests but increases enzyme activity and improves the community structure of VF biofilms, which is beneficial for the wastewater disposal. PMID- 26538258 TI - Level of contamination by metallic trace elements and organic molecules in the seagrass beds of Guadeloupe Island. AB - Seagrass bed ecosystems occupy the most important part of coastal shelf in the French West Indies. They also constitute nurseries for many invertebrates and fishes harvested by local fisheries. In Guadeloupe, coastal fish stocks are declining meanwhile several agroecosystems revealed to be heavily contaminated by pollutants (agricultural lands, rivers, mangroves, seagrass beds, and coral reefs). Considering these facts, a study of the contamination of seagrass beds (8000 ha) of the Grand Cul-de-Sac Marin (GCSM) bay was conducted on their sediments and marine phanerogams. The analyses concerned six metals (Cd, Cu, Hg, Pb, V, Zn), tributyltin, 18 polycyclic aromatic hydrocarbons (PAHs), eight polybrominated diphenyl ethers (PBDEs), 38 polychlorobiphenyls (PCBs), dithiocarbamates (CS2 residues), and 225 pesticide molecules.Overall, the level of contamination of the seagrass beds was low for both sediments and phanerogams. Metallic trace elements were the main pollutants but with higher concentrations recorded in coastal sites, and their distribution can be explained by the proximity of river mouths and current patterns. The level of contamination was lower in plants than in sediments. However, the level of contamination between these two compartments was significantly correlated. The conclusion of this study is that, unlike other coastal ecosystems of Guadeloupe such as mangroves, the seagrass beds in the GCSM present a low degree of pollution. The observed level of contaminants does not seem to threaten the role of nursery played by the seagrass beds and does not likely present a risk for the reintroduction of manatees. PMID- 26538259 TI - Comparison of UV/hydrogen peroxide and UV/peroxydisulfate processes for the degradation of humic acid in the presence of halide ions. AB - This study compared the behaviors of two classic advanced oxidation processes (AOPs), hydroxyl radical-based AOPs ((*)OH-based AOPs) and sulfate radical-based AOPs (SO4 (*-)-based AOPs), represented by UV/ hydrogen peroxide (H2O2) and UV/peroxydisulfate (PDS) systems, respectively, to degrade humic acid (HA) in the presence of halide ions (Cl(-) and Br(-)). The effects of different operational parameters, such as oxidant dosages, halide ions concentration, and pH on HA degradation were investigated in UV/H2O2/Cl(-), UV/PDS/Cl(-), UV/H2O2/Br(-), and UV/PDS/Br(-) processes. It was found that the oxidation capacity of H2O2 and PDS to HA degradation in the presence of halides was nearly in the same order. High dosage of peroxides would lead to an increase in HA removal while excess dosage would slightly inhibit the efficiency. Both Cl(-) and Br(-) would have depressing impact on the two AOPs, but the inhibiting effect of Br(-) was more obvious than that of Cl(-), even the concentration of Cl(-) was far above that of Br(-). The increasing pH would have an adverse effect on HA decomposition in UV/H2O2 system, whereas there was no significant impact of pH in UV/PDS process. Furthermore, infrared spectrometer was used to provide the information of degraded HA in UV/H2O2/Cl(-), UV/PDS/Cl(-), UV/H2O2/Br(-), and UV/PDS/Br(-) processes, and halogenated byproducts were identified in using GC-MS analysis in the four processes. The present research might have significant technical implications on water treatment using advanced oxidation technologies. PMID- 26538260 TI - Vertical profile, source apportionment, and toxicity of PAHs in sediment cores of a wharf near the coal-based steel refining industrial zone in Kaohsiung, Taiwan. AB - Three sediment cores were collected from a wharf near a coal-based steel refining industrial zone in Kaohsiung, Taiwan. Analyses for 16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection Agency priority list in the core sediment samples were conducted using gas chromatography-mass spectrometry. The vertical profiles of PAHs in the core sediments were assessed, possible sources and apportionment were identified, and the toxicity risk of the core sediments was determined. The results from the sediment analyses showed that total concentrations of the 16 PAHs varied from 11774 +/- 4244 to 16755 +/- 4593 ng/g dry weight (dw). Generally, the vertical profiles of the PAHs in the sediment cores exhibited a decreasing trend from the top to the lower levels of the S1 core and an increasing trend of PAHs from the top to the lower levels of the S2 and S3 cores. Among the core sediment samples, the five- and six-ring PAHs were predominantly in the S1 core, ranging from 42 to 54 %, whereas the composition of the PAHs in the S2 and S3 cores were distributed equally across three groups: two- and three-ring, four-ring, and five- and six-ring PAHs. The results indicated that PAH contamination at the site of the S1 core had a different source. The molecular indices and principal component analyses with multivariate linear regression were used to determine the source contributions, with the results showing that the contributions of coal, oil-related, and vehicle sources were 38.6, 35.9, and 25.5 %, respectively. A PAH toxicity assessment using the mean effect range-median quotient (m-ERM-q, 0.59-0.79), benzo[a]pyrene toxicity equivalent (TEQ(carc), 1466-1954 ng TEQ/g dw), and dioxin toxicity equivalent (TEQ(fish), 3036-4174 pg TEQ/g dw) identified the wharf as the most affected area. The results can be used for regular monitoring, and future pollution prevention and management should target the coal-based industries in this region for pollution reduction. PMID- 26538261 TI - Seawater influence monitored by NaCl on the growth of Trametes versicolor. AB - There are only a few scientific data about the function of ecosystems after tsunami disasters. The ecosystems help the environment to recover after a disaster, and therefore, the research on its function is important. We estimated the seawater influences on wood degradation after a tsunami disaster by the growth of Trametes versicolor. The debris from the Great East Japan Earthquake on the pacific coast in March 2011 was used for the simulations. Its growth on debris was compared with those on seawater-treated woods, and the amount of sodium chloride was examined to know the approximate amount of salts in the samples. Sodium chloride contents were employed as an indicative parameter of sea salts, which contained many elements. As a result, this common white-rot fungus degraded wood debris in the same way as sound sapwood. Although the study was conducted at the laboratory level, this is the first report from the real debris, which assessed the fungal decomposition ability of the ecosystem after a tsunami disaster. PMID- 26538262 TI - Health risk equations and risk assessment of airborne benzene homologues exposure to drivers and passengers in taxi cabins. AB - Interior air environment and health problems of vehicles have attracted increasing attention, and benzene homologues (BHs) including benzene, toluene, ethylbenzene, xylenes, and styrene are primary hazardous gases in vehicular cabins. The BHs impact on the health of passengers and drivers in 38 taxis is assessed, and health risk equations of in-car BHs to different drivers and passengers are induced. The health risk of in-car BHs for male drivers is the highest among all different receptors and is 1.04, 6.67, and 6.94 times more than ones for female drivers, male passengers, and female passengers, respectively. In car BHs could not lead to the non-cancer health risk to all passengers and drivers as for the maximal value of non-cancer indices is 0.41 and is less than the unacceptable value (1.00) of non-cancer health risk from USEPA. However, in car BHs lead to cancer health risk to drivers as for the average value of cancer indices is 1.21E-04 which is 1.21 times more than the unacceptable value (1.00E 04) of cancer health risk from USEPA. Finally, for in-car airborne benzene concentration (X, MUg/m(3)) to male drivers, female drivers, male passengers, and female passengers, the cancer health risk equations are Y = 1.48E-06X, Y = 1.42E 06X, Y = 2.22E-07X, and Y = 2.13E-07X, respectively, and the non-cancer health risk equations are Y = 1.70E-03X, Y = 1.63E-03X, Y = 2.55E-04X, and Y = 2.45E 04X, respectively. PMID- 26538264 TI - Erratum to: Continuously elevated serum matrix metalloproteinase-3 for 3 ~ 6 months predict one-year radiographic progression in rheumatoid arthritis: a prospective cohort study. PMID- 26538263 TI - Evidence for the Importance of Vitamin D Status in Neurologic Conditions. AB - OPINION STATEMENT: Vitamin D status has been proposed as relevant to many neurological disorders. Data suggest that vitamin D may be important for the development of the nervous system, and it also plays a role in neuroimmunology and neuroprotection. Lower levels of circulating 25-hydroxyvitamin D have been linked with increased risk of multiple sclerosis (MS) and Alzheimer's disease (AD). While people with amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and stroke have lower vitamin D levels than those without the diseases, it is unclear if this is because hypovitaminosis D contributes to disease risk or is a consequence of immobility and other factors caused by the disease. Lower levels of vitamin D have been associated with worse prognosis in MS, PD, ALS, and stroke, while no longitudinal studies have been performed to evaluate such an association in AD. Small pilot trials have been performed to evaluate vitamin D supplementation for some of these diseases, but there have been no phase III studies to support vitamin D supplementation in these patient populations; further, ideal levels of 25-hydroxyvitamin D are not known. Thus, while some expert panels or individuals have suggested routine testing and supplementation for patients with these neurological conditions, it is our opinion that there are currently insufficient data to support high-dose vitamin D supplementation to specifically treat or prevent these conditions. PMID- 26538266 TI - Radiological and functional outcomes 2.7 years following conservatively treated completely displaced midshaft clavicle fractures. AB - OBJECTIVES: It is unclear whether all completely displaced midshaft clavicle fractures require primary surgical intervention. The aim of this study was to elucidate the radiological and clinical outcomes after conservative treatment, and to identify subgroups at risk of an inferior outcome. DESIGN: Retrospective case series. SETTING: Level II trauma center. PATIENTS: Between 2005 and 2008, 122 patients were conservatively treated for a completely displaced midshaft clavicle fracture of whom 92 were eligible for inclusion in this study. Of these, 59 completed the study after a median of 2.7 years after the fracture (min-max, 1.1-4.9). INTERVENTION: The patients received the standard treatment administered at our institution at the time: nonsurgically with a sling without physiotherapy. Patients with painful nonunions were subsequently offered surgery. MAIN OUTCOME MEASUREMENTS: At follow-up, the patients' Disabilities of Arm, Shoulder, and Hand (DASH) and the Constant scores were evaluated. Radiographs were taken at follow up and compared to those taken acutely. RESULTS: Nonunion was found in 9 of the 59 (15.3%) patients. Twenty-four (24%) patients reported a fair-to-poor DASH score (i.e. >20). Patients with fractures that were vertically displaced by more than 100% (one bone width) were significantly less satisfied than those with fractures vertically displaced at 100% (p = 0.04). Initial shortening of more than 15 mm was not associated with a worse outcome or nonunion. The odds ratio of developing a nonunion increased with age (p = 0.04). CONCLUSIONS: By treating completely displaced midshaft clavicle fractures conservatively with a sling and offering plate fixation for eventual painful nonunions, we found a 24% risk of a fair or poor clinical result with a DASH score over 20. A vertical displacement of more than 100 % between the main fragments on the initial radiograph was associated with an inferior clinical outcome in this study. LEVEL OF EVIDENCE: IV. PMID- 26538265 TI - Molecular changes in the medial prefrontal cortex and nucleus accumbens are associated with blocking the behavioral sensitization to cocaine. AB - Previous studies have demonstrated that cocaine-induced behavioral sensitization is associated with persistent functional and structural alterations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc); however, the molecular mechanisms underlying these changes have not been elucidated. In this study, the behavioral sensitization to cocaine was established in Sprague Dawley rats and was measured by locomotion and behavioral rating. The brain tissue homogenization was used for measuring the level of brain-derived neurotrophic factor (BDNF), the expression and activity of integrin-linked kinase (ILK), level of protein kinase B (Akt) phosphorylation at serine 473 and threonine 308, and the expression of p75(NTR), TrkA, and TrkB protein. The Results showed that cocaine sensitization was associated with increased BDNF, ILK activity, phospho-Akt Ser(473), p75(NTR), and TrkB protein levels in the mPFC and NAc core. The combination of pergolide and ondansetron normalized not only behavioral sensitization, but also the increases in these molecular markers. Dual immunofluoresence staining showed that ILK expression is co-distributed with p75(NTR) and TrkA expression in both the mPFC and NAc core. Results suggested that the BDNF-TrkA/p75(NTR)-ILK-Akt signaling pathway may be active in cocaine sensitization and associated neural plasticity in the mPFC and NAc core. PMID- 26538267 TI - Daily Fluctuations in Everyday Cognition: Is It Meaningful? AB - OBJECTIVE: This study examined whether there are daily fluctuations in everyday cognition that are consistent with daily fluctuations often observed in traditional measures of basic cognitive abilities. METHOD: Two hundred six independently living older adults (age range = 60-91 years) were asked to complete a computerized cognitive battery over eight occasions within a 2- to 3 week period. RESULTS: Using multilevel model, significant within-person variability was observed across the Daily Everyday Cognition Assessment (DECA; 46%), with 54% between-person variability. At each occasion, better performance on the DECA was significantly associated with better performance on simple reaction time ( p < .01) and memory (Auditory Verbal Learning Task, p < .01) even after accounting for time, age, education, and performance on other cognitive measures. CONCLUSION: These findings demonstrate that within-person performance fluctuations can be observed for everyday cognition tasks, and these fluctuations are consistent with daily changes in basic cognitive abilities. PMID- 26538268 TI - Caregiving, Transport-Related, and Demographic Correlates of Sedentary Behavior in Older Adults: The Senior Neighborhood Quality of Life Study. AB - OBJECTIVE: Excess sedentary time predicts negative health outcomes independent of physical activity. The present investigation examined informal caregiving duties and transportation-related factors as potential correlates of sedentary behavior in older adults. METHOD: Average daily sedentary time was measured via accelerometer in adults ages 66 years and older (N = 861). Caregiving variables included dog ownership and informal family caregiving status. Transportation variables included driver status, walking distance to public transit, and reported presence of pedestrians and bicyclists in one's neighborhood. RESULTS: In multivariate models, owning a dog and being a driver were associated with less sedentary time (p <= .01). Educational status and geographic region modified the association between dog ownership and sedentary time, and age modified the association between driver status and sedentary time. DISCUSSION: This study identified that older adult dog owners and drivers were less sedentary. Both factors may create opportunities for older adults to get out of their homes. PMID- 26538269 TI - Neurology in evolution 2014-2015. PMID- 26538270 TI - Corrigendum. PMID- 26538271 TI - Intracranial pressure and hypercapnia during the apnoea test for the diagnosis of brain death. PMID- 26538272 TI - The clinical determination of brain death: practice limitations. PMID- 26538274 TI - Cardiac Denial and Psychological Predictors of Cardiac Care Adherence in Adults With Congenital Heart Disease. AB - The current study examined cardiac denial and psychological predictors (i.e., depression, anxiety) of health outcomes including medical nonadherence and physical health in a sample of 80 adults with congenital heart disease (ACHD). Results indicated that denial of impact was elevated in this patient group compared with reference groups, and denial was negatively associated with depression and anxiety at ps < .01. Results indicated that depression, anxiety, and denial predicted unique variance in medical nonadherence, and gender moderated the relationships between these psychological factors and nonadherence. For depression, men and women showed similar relationships between depression and nonadherence at high levels of depression; however, at low levels of depression (i.e., a more normal mood state), men were less adherent compared with women. For anxiety, men and women did not differ in adherence at low levels of anxiety; however, men experiencing high anxiety were less adherent compared with women experiencing high anxiety. Implications of this study are discussed including the role of gender and denial and the impact of denial functioning to reduce negative affect. Depression was the only significant predictor of physical functioning. Results of this study suggest that psychological interventions aimed at depression and anxiety may function differently across gender to improve patient medical adherence and improve physical functioning in ACHD. PMID- 26538275 TI - Anxiety Sensitivity and Smoking Behavior Among Trauma-Exposed Daily Smokers: The Explanatory Role of Smoking-Related Avoidance and Inflexibility. AB - Anxiety sensitivity (AS), defined as the extent to which individuals believe that anxiety-related sensations have harmful consequences, is associated with smoking processes and poorer clinical outcomes among trauma-exposed smokers. Yet the specific mechanisms underlying this association are unclear. Smoking-specific avoidance and inflexibility is a construct implicated in multiple manifestations of mood regulation that may underlie smoking behavior. The current study examined the explanatory role of smoking-specific avoidance and inflexibility in terms of the relation between AS and indices of smoking behavior among trauma-exposed smokers. The sample consisted of 217 treatment-seeking adult smokers (44% female; M age = 37.8; SD = 13.2; age range: 18-65 years), who were exposed to at least one lifetime Criterion A trauma event (Diagnostic and Statistical Manual of Mental Disorders [4th ed., text rev.; DSM-IV-TR] Criterion A for trauma exposure). Bootstrap analysis (5,000 re-samples) revealed that AS was indirectly related to the (a) number of cigarettes smoked per day, (b) number of years being a daily smoker, (c) number of failed quit attempts, and (d) heaviness of smoking index among trauma-exposed smokers through its relation with smoking-specific avoidance and inflexibility. These findings provide initial evidence suggesting that smoking-specific avoidance and inflexibility may be an important construct in better understanding AS-smoking relations among trauma-exposed smokers. Future work is needed to explore the extent to which smoking-specific avoidance and inflexibility account for relations between AS and other smoking processes (e.g., withdrawal, cessation outcome) in the context of trauma and smoking comorbidity. PMID- 26538276 TI - Using Single-Case Experiments to Support Evidence-Based Decisions: How Much Is Enough? AB - For practitioners, the use of single-case experimental designs (SCEDs) in the research literature raises an important question: How many single-case experiments are enough to have sufficient confidence that an intervention will be effective with an individual from a given population? Although standards have been proposed to address this question, current guidelines do not appear to be strongly grounded in theory or empirical research. The purpose of our article is to address this issue by presenting guidelines to facilitate evidence-based decisions by adopting a simple statistical approach to quantify the support for interventions that have been validated using SCEDs. Specifically, we propose the use of success rates as a supplement to support evidence-based decisions. The proposed methodology allows practitioners to aggregate the results from single case experiments to estimate the probability that a given intervention will produce a successful outcome. We also discuss considerations and limitations associated with this approach. PMID- 26538277 TI - Comparison of serological assays in human Middle East respiratory syndrome (MERS) coronavirus infection. AB - Plaque reduction neutralisation tests (PRNT), microneutralisation (MN), Middle East respiratory syndrome (MERS)-spike pseudoparticle neutralisation (ppNT) and MERS S1-enzyme-linked immunosorbent assay (ELISA) antibody titres were compared using 95 sera from 17 patients with MERS, collected two to 46 days after symptom onset. Neutralisation tests correlated well with each other and moderately well with S1 ELISA. Moreover to compare antigenic similarity of genetically diverse MERS-CoV clades, the response of four sera from two patients sampled at two time periods during the course of illness were tested by 90% PRNT. Genetically diverse MERS-CoV clades were antigenically homogenous. PMID- 26538278 TI - Doxorubicin-conjugated beta-NaYF4:Gd(3+)/Tb(3+) multifunctional, phosphor nanorods: a multi-modal, luminescent, magnetic probe for simultaneous optical and magnetic resonance imaging and an excellent pH-triggered anti-cancer drug delivery nanovehicle. AB - Herein, we report the fabrication of a multifunctional nanoprobe based on highly monodispersed, optically and magnetically active, biocompatible, PEI functionalized, highly crystalline beta-NaYF4:Gd(3+)/Tb(3+) nanorods as an excellent multi-modal optical/magnetic imaging tool and a pH-triggered intracellular drug delivery nanovehicle. The static and dynamic photoluminescence spectroscopy showed the presence of sharp emission peaks, with long lifetimes (~3.5 milliseconds), suitable for optical imaging. The static magnetic susceptibility measurements at room temperature showed a strong paramagnetic signal (chi~ 3.8 * 10(-5) emu g(-1) Oe(-1)). The nuclear magnetic resonance (NMR) measurements showed fair T1 relaxivity (r1 = 1.14 s(-1) mM(-1)) and magnetic resonance imaging gave enhanced T1-weighted MRI images with increased concentrations of beta-NaYF4:Gd(3+)/Tb(3+) making them suitable for simultaneous magnetic resonance imaging. In addition, an anticancer drug, doxorubicin (DOX) was conjugated to the amine-functionalized beta-NaYF4:Gd(3+)/Tb(3+) nanorods via pH-sensitive hydrazone bond linkages enabling them as a pH-triggered, site specific drug delivery nanovehicle for DOX release inside tumor cells. A comparison between in vitro DOX release studies undertaken in normal physiological (pH 7.4) and acidic (pH 5.0) environments showed an enhanced DOX dissociation (~80%) at pH 5.0. The multifunctional material was also applied as an optical probe to confirm the conjugation of DOX and to monitor DOX release via a fluorescence resonance energy transfer (FRET) mechanism. The DOX-conjugated beta-NaYF4:Gd(3+)/Tb(3+) nanorods exhibited a cytotoxic effect on MCF-7 breast cancer cells and their uptake by MCF-7 cells was demonstrated using confocal laser scanning microscopy and flow cytometry. The comparative cellular uptakes of free DOX and DOX-conjugated beta-NaYF4:Gd(3+)/Tb(3+) nanorods were studied in tumor microenvironment conditions (pH 6.5) using confocal imaging, which showed an increased uptake of DOX-conjugated beta-NaYF4:Gd(3+)/Tb(3+) nanorods. Thus, DOX-conjugated beta-NaYF4:Gd(3+)/Tb(3+) nanorods combining pH-triggered drug delivery, efficient luminescence and paramagnetic properties are promising for a potential multifunctional platform for cancer therapy, biodetection, and optical and magnetic resonance imaging. PMID- 26538279 TI - Oufti: an integrated software package for high-accuracy, high-throughput quantitative microscopy analysis. AB - With the realization that bacteria display phenotypic variability among cells and exhibit complex subcellular organization critical for cellular function and behavior, microscopy has re-emerged as a primary tool in bacterial research during the last decade. However, the bottleneck in today's single-cell studies is quantitative image analysis of cells and fluorescent signals. Here, we address current limitations through the development of Oufti, a stand-alone, open-source software package for automated measurements of microbial cells and fluorescence signals from microscopy images. Oufti provides computational solutions for tracking touching cells in confluent samples, handles various cell morphologies, offers algorithms for quantitative analysis of both diffraction and non diffraction-limited fluorescence signals and is scalable for high-throughput analysis of massive datasets, all with subpixel precision. All functionalities are integrated in a single package. The graphical user interface, which includes interactive modules for segmentation, image analysis and post-processing analysis, makes the software broadly accessible to users irrespective of their computational skills. PMID- 26538280 TI - Usefullness of three-dimensional templating software to quantify the contact state between implant and femur in total hip arthroplasty. AB - BACKGROUND: It would be ideal if surgeons could precisely confirm whether the planned femoral component achieves the best fit and fill of implant and femur. However, the cortico-cancellous interfaces can be difficult to standardize using plain radiography, and therefore, determining the contact state is a subjective decision by the examiner. Few reports have described the use of CT-based three dimensional templating software to quantify the contact state of stem and femur in detail. The purpose of this study was to use three-dimensional templating software to quantify the implant-femur contact state and develop a technique to analyze the initial fixation pattern of a cementless femoral stem. METHODS: We conducted a retrospective review of 55 hips in 53 patients using a short proximal fit-and-fill anatomical stem (APS Natural-HipTM System). All femurs were examined by density mapping which can visualize and digitize the contact state. We evaluated the contact state of implant and femur by using density mapping. RESULTS: The varus group (cases that had changed varus 2 degrees by 3 months after surgery) consisted of 11 hips. The varus group showed no significant difference with regard to cortical contact in the proximal medial portion (Gruen 7), but the contact area in the distal portion (Gruen 3 and Gruen 5) was significantly lower than that of non-varus group. Density mapping showed that the stem only has to be press-fit to the medial calcar, but also must fill the distal portion of the implant in order to achieve the ideal contact state. CONCLUSIONS: Our results indicated that quantifying the contact state of implant and femur by using density mapping is a useful technique to accurately analyze the fixation pattern of a cementless femoral stem. PMID- 26538281 TI - Complex patterns of signalling to convey different social goals of sex in bonobos, Pan paniscus. AB - Sexual behaviour in bonobos (Pan paniscus) functions beyond mere reproduction to mediate social interactions and relationships. In this study, we assessed the signalling behaviour in relation to four social goals of sex in this species: appeasement after conflict, tension reduction, social bonding and reproduction. Overall, sexual behaviour was strongly decoupled from its ancestral reproductive function with habitual use in the social domain, which was accompanied by a corresponding complexity in communication behaviour. We found that signalling behaviour varied systematically depending on the initiator's goals and gender. Although all gestures and vocalisations were part of the species-typical communication repertoire, they were often combined and produced flexibly. Generally, gestures and multi-modal combinations were more flexibly used to communicate a goal than vocalisations. There was no clear relation between signalling behaviour and success of sexual initiations, suggesting that communication was primarily used to indicate the signaller's intention, and not to influence a recipient's willingness to interact sexually. We discuss these findings in light of the larger question of what may have caused, in humans, the evolutionary transition from primate-like communication to language. PMID- 26538282 TI - Diel Variation in Flower Scent Reveals Poor Consistency of Diurnal and Nocturnal Pollination Syndromes in Sileneae. AB - The composition of flower scent and the timing of emission are crucial for chemical communication between plants and their pollinators; hence, they are key traits for the characterization of pollination syndromes. In many plants, however, plants are assigned to a syndrome based on inexpensive to measure flower traits, such as color, time of flower opening, and shape. We compared day and night scents from 31 Sileneae species and tested for quantitative and semi quantitative differences in scent among species classified a priori as diurnal or nocturnal. As most Sileneae species are not only visited by either diurnal or nocturnal animals as predicted by their syndrome, we hypothesized that, even if flower scent were preferentially emitted during the day or at night, most species also would emit some scents during the opposing periods of the day. This phenomenon would contribute to the generalized assemblage of flower visitors usually observed in Sileneae species. We found that diel variations of scent often were not congruent with the syndrome definition, but could partially be explained by taxonomy and sampling times. Most species emitted compounds with attractive potential to insects during both the night and day. Our results highlight the current opinion that syndromes are not watertight compartments evolved to exclude some flower visitors. Thus, important information may be lost when scents are collected either during day- or night-time, depending on the a priori classification of the species as diurnal or nocturnal. PMID- 26538283 TI - Structural Characterization of a Newly Identified Component of alpha Carboxysomes: The AAA+ Domain Protein CsoCbbQ. AB - Carboxysomes are bacterial microcompartments that enhance carbon fixation by concentrating ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and its substrate CO2 within a proteinaceous shell. They are found in all cyanobacteria, some purple photoautotrophs and many chemoautotrophic bacteria. Carboxysomes consist of a protein shell that encapsulates several hundred molecules of RuBisCO, and contain carbonic anhydrase and other accessory proteins. Genes coding for carboxysome shell components and the encapsulated proteins are typically found together in an operon. The alpha-carboxysome operon is embedded in a cluster of additional, conserved genes that are presumably related to its function. In many chemoautotrophs, products of the expanded carboxysome locus include CbbO and CbbQ, a member of the AAA+ domain superfamily. We bioinformatically identified subtypes of CbbQ proteins and show that their genes frequently co-occur with both Form IA and Form II RuBisCO. The alpha-carboxysome associated ortholog, CsoCbbQ, from Halothiobacillus neapolitanus forms a hexamer in solution and hydrolyzes ATP. The crystal structure shows that CsoCbbQ is a hexamer of the typical AAA+ domain; the additional C-terminal domain, diagnostic of the CbbQ subfamily, structurally fills the inter-monomer gaps, resulting in a distinctly hexagonal shape. We show that CsoCbbQ interacts with CsoCbbO and is a component of the carboxysome shell, the first example of ATPase activity associated with a bacterial microcompartment. PMID- 26538284 TI - Defining ATM-Independent Functions of the Mre11 Complex with a Novel Mouse Model. AB - The Mre11 complex (Mre11, Rad50, and Nbs1) occupies a central node of the DNA damage response (DDR) network and is required for ATM activation in response to DNA damage. Hypomorphic alleles of MRE11 and NBS1 confer embryonic lethality in ATM-deficient mice, indicating that the complex exerts ATM-independent functions that are essential when ATM is absent. To delineate those functions, a conditional ATM allele (ATM(flox)) was crossed to hypomorphic NBS1 mutants (Nbs1(DeltaB/DeltaB) mice). Nbs1(DeltaB/DeltaB) Atm(-/-) hematopoietic cells derived by crossing to vav(cre) were viable in vivo. Nbs1(DeltaB/DeltaB) Atm(-/-) (VAV) mice exhibited a pronounced defect in double-strand break repair and completely penetrant early onset lymphomagenesis. In addition to repair defects observed, fragile site instability was noted, indicating that the Mre11 complex promotes genome stability upon replication stress in vivo. The data suggest combined influences of the Mre11 complex on DNA repair, as well as the responses to DNA damage and DNA replication stress. IMPLICATIONS: A novel mouse model was developed, by combining a vav(cre)-inducible ATM knockout mouse with an NBS1 hypomorphic mutation, to analyze ATM-independent functions of the Mre11 complex in vivo. These data show that the DNA repair, rather than DDR signaling functions of the complex, is acutely required in the context of ATM deficiency to suppress genome instability and lymphomagenesis. PMID- 26538286 TI - The sense of the body in the dream: Diagnostic capacity in the meanings of dreams. AB - The author investigates the oneiric representation of somatic states and the diagnostic capacity of dreams. He draws on Freud's hypotheses on the procedures by which somatic stimuli insert themselves in oneiric elaboration and restructures them according to the recent neurobiological discoveries and to analytical experiences. In the representations of certain dreams, with a psychic interpretation agreed upon by the patients, somatic alterations unknown to the analytical couple were discriminated and confirmed by radiological investigations. These representations were linked to the manifestation of one aspect of the bodily Self, neglected in the precocious maternal relation, that entered the organization of the Self consolidated in the relation with the paternal figure. This conjunction gave origin to the double meaning (somatic and psychic) of the dream. The entering of the somatic representation in the oneiric one did not appear to be the figurative effect, but of a condensation of diagnostic capacity into the meaning of the dream. This characteristic manifested itself in the particular styles of the dreamers, interpretable by an analyst countertransferentially oriented. The perception or scotomization of the condensation in the interpretation of the dream and of the moment had an effect on the evolution of the analysis. PMID- 26538285 TI - Linking Cancer Metabolism to DNA Repair and Accelerated Senescence. AB - Conventional wisdom ascribes metabolic reprogramming in cancer to meeting increased demands for intermediates to support rapid proliferation. Prior models have proposed benefits toward cell survival, immortality, and stress resistance, although the recent discovery of oncometabolites has shifted attention to chromatin targets affecting gene expression. To explore further effects of cancer metabolism and epigenetic deregulation, DNA repair kinetics were examined in cells treated with metabolic intermediates, oncometabolites, and/or metabolic inhibitors by tracking resolution of double-strand breaks (DSB) in irradiated MCF7 breast cancer cells. Disrupting cancer metabolism revealed roles for both glycolysis and glutaminolysis in promoting DSB repair and preventing accelerated senescence after irradiation. Targeting pathways common to glycolysis and glutaminolysis uncovered opposing effects of the hexosamine biosynthetic pathway (HBP) and tricarboxylic acid (TCA) cycle. Treating cells with the HBP metabolite N-acetylglucosamine (GlcNAc) or augmenting protein O-GlcNAcylation with small molecules or RNAi targeting O-GlcNAcase each enhanced DSB repair, while targeting O-GlcNAc transferase reversed GlcNAc's effects. Opposing the HBP, TCA metabolites including alpha-ketoglutarate blocked DSB resolution. Strikingly, DNA repair could be restored by the oncometabolite 2-hydroxyglutarate (2-HG). Targeting downstream effectors of histone methylation and demethylation implicated the PRC1/2 polycomb complexes as the ultimate targets for metabolic regulation, reflecting known roles for Polycomb group proteins in nonhomologous end-joining DSB repair. Our findings that epigenetic effects of cancer metabolic reprogramming may promote DNA repair provide a molecular mechanism by which deregulation of metabolism may not only support cell growth but also maintain cell immortality, drive therapeutic resistance, and promote genomic instability. IMPLICATIONS: By defining a pathway from deregulated metabolism to enhanced DNA damage response in cancer, these data provide a rationale for targeting downstream epigenetic effects of metabolic reprogramming to block cancer cell immortality and overcome resistance to genotoxic stress. PMID- 26538287 TI - Reliability and criterion validity of an observation protocol for working technique assessments in cash register work. AB - We evaluated the intra- and inter-observer reliability and criterion validity of an observation protocol, developed in an iterative process involving practicing ergonomists, for assessment of working technique during cash register work for the purpose of preventing upper extremity symptoms. Two ergonomists independently assessed 17 15-min videos of cash register work on two occasions each, as a basis for examining reliability. Criterion validity was assessed by comparing these assessments with meticulous video-based analyses by researchers. Intra-observer reliability was acceptable (i.e. proportional agreement >0.7 and kappa >0.4) for 10/10 questions. Inter-observer reliability was acceptable for only 3/10 questions. An acceptable inter-observer reliability combined with an acceptable criterion validity was obtained only for one working technique aspect, 'Quality of movements'. Thus, major elements of the cashiers' working technique could not be assessed with an acceptable accuracy from short periods of observations by one observer, such as often desired by practitioners. Practitioner Summary: We examined an observation protocol for assessing working technique in cash register work. It was feasible in use, but inter-observer reliability and criterion validity were generally not acceptable when working technique aspects were assessed from short periods of work. We recommend the protocol to be used for educational purposes only. PMID- 26538288 TI - A qualitative study of treatment-seeking heroin users in contemporary China. AB - BACKGROUND: Heroin has emerged as the primary drug of concern in China, with as many as three million contemporary users. Once a Chinese citizen has been identified by Chinese law enforcement as a 'drug addict', that individual is 'registered' in an official government tracking system for the rest of his or her life, independent of verified rehabilitation and recovery. Most of what is known about heroin users in China is based on studies of registered heroin users participating, often involuntarily, in government-sponsored treatment. METHODS: Using Grounded Theory Methodology, we collected and analyzed in-depth interviews of heroin users voluntarily seeking treatment at a new, non-government-sponsored, for-profit, addiction treatment hospital in Beijing, China. RESULTS: We identified three major themes among our participants: (1) intense social stigma towards individuals with drug addiction; (2) a desire for anonymous, confidential treatment to avoid social stigma and the loss of personal freedom that accompanies participation in government-sponsored treatment; and (3) a deep mistrust of government-sponsored treatment and a search for more effective alternatives. CONCLUSION: Despite a desire for treatment, our subjects were reluctant to access government-sponsored treatment facilities because of fear of a stigmatized identity, fear of loss of personal freedom, and lack of faith in the efficacy and safety of government-sponsored treatments. Their willingness to pay cash at a new, non-government-sponsored, addiction treatment facility illustrates the lengths to which they will go to remain 'unregistered' and to discover better alternatives. That the Chinese government allows such facilities to operate outside of government surveillance suggests a new openness to alternative options to combat China's rising drug epidemic. The efficacy of these alternative options, however, remains in question. PMID- 26538289 TI - Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome. AB - Tourette syndrome (TS) is a neurological disorder characterized by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit (CSTC) dysfunction and hyperexcitability of cortical limbic and motor regions, which are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by 'premonitory sensory phenomena' (PSP) that are described as uncomfortable cognitive or bodily sensations that precede the execution of a tic, and are experienced as a strong urge for motor discharge. While the precise role played by PSP in the occurrence of tics is controversial, PSP are nonetheless of considerable theoretical and clinical importance in TS, not least because they form the core component in many of the behavioural therapies that are currently used in the treatment of tic disorders. In this study, we investigated the brain structure correlates of PSP. Specifically, we conducted a whole-brain analysis of cortical (grey matter) thickness in 29 children and young adults with TS and investigated the association between grey matter thickness and PSP. We demonstrate for the first time that PSP are inversely associated with grey matter thickness measurements within the insula and sensorimotor cortex. We also demonstrate that grey matter thickness is significantly reduced in these areas in individuals with TS relative to a closely age- and gender-matched group of typically developing individuals and that PSP ratings are significantly correlated with tic severity. PMID- 26538290 TI - Within-species reproductive costs affect the asymmetry of satyrization in Drosophila. AB - Understanding how species interactions influence their distribution and evolution is a fundamental question in evolutionary biology. Theory suggests that asymmetric reproductive interference, in which one species induces higher reproductive costs on another species, may be more important in delimiting species boundaries than interspecific competition over resources. However, the underlying mechanisms of such asymmetry remain unclear. Here, we test whether differences in within-species reproductive costs determine the between-species asymmetry of costs using three allopatric Drosophila species belonging to the melanogaster subgroup. Our results support this hypothesis, especially in a pair of insular species. Males of one species that induce costs to their conspecific females led to a 5-fold increase of heterospecific females mortality with dead flies bearing spectacular large melanized wounds on their genitalia. Males of the other species were harmful neither to their conspecific nor heterospecific females. Comparative studies of within-species reproductive costs may therefore be a valuable tool for predicting between-species interactions and community structures. PMID- 26538291 TI - Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury. AB - To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either "with HAL suitability" or "without HAL suitability" based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID- 26538292 TI - Alterations in serotonin metabolism in the irritable bowel syndrome. AB - BACKGROUND: Alterations in serotonin (5-HT) metabolism have been postulated to play a role in the pathogenesis of irritable bowel syndrome (IBS). However, previous reports regarding 5-HT metabolism in IBS are contradicting. AIM: To compare platelet poor plasma (PPP) 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels and their ratio in a large cohort of IBS patients and healthy controls (HC), including IBS-subgroup analysis. METHODS: Irritable bowel syndrome patients and HC were evaluated for fasting PPP 5-HT and 5-HIAA levels. Furthermore, GI symptom diary, GSRS, quality of life, anxiety and depression scores were assessed in the 2 weeks before blood sampling. RESULTS: One hundred and fifty four IBS patients and 137 HC were included. No differences were detected in plasma 5-HT between groups. The 5-HIAA concentrations and 5-HIAA/5-HT ratio were significantly lower in IBS compared to HC: 24.6 +/- 21.9 vs. 39.0 +/- 29.5 MUg/L (P < 0.001) and 8.4 +/- 12.2 vs. 13.5 +/- 16.6 (P < 0.01), respectively. Subtype analysis for 5-HIAA showed all IBS subtypes to be significantly different from HC. The 5-HIAA/5-HT ratio was significantly lower in the IBS-M subtype vs. HC. Linear regression analysis points to an influence of gender but not of GI symptoms, psychological scores or medication use. CONCLUSIONS: We demonstrated that fasting 5-HT plasma levels are not significantly different in IBS patients compared to controls. However, decreased 5-HIAA levels and 5-HIAA/5-HT ratio in IBS patients may reflect altered serotonin metabolism in IBS. Gender affects 5 HIAA levels in IBS patients, but no effects of drugs, such as SSRIs, or higher GI symptom or psychological scores were found. PMID- 26538293 TI - Integrated active sensor system for real time vibration monitoring. AB - We report a self-powered, lightweight and cost-effective active sensor system for vibration monitoring with multiplexed operation based on contact electrification between sensor and detected objects. The as-fabricated sensor matrix is capable of monitoring and mapping the vibration state of large amounts of units. The monitoring contents include: on-off state, vibration frequency and vibration amplitude of each unit. The active sensor system delivers a detection range of 0 60 Hz, high accuracy (relative error below 0.42%), long-term stability (10000 cycles). On the time dimension, the sensor can provide the vibration process memory by recording the outputs of the sensor system in an extend period of time. Besides, the developed sensor system can realize detection under contact mode and non-contact mode. Its high performance is not sensitive to the shape or the conductivity of the detected object. With these features, the active sensor system has great potential in automatic control, remote operation, surveillance and security systems. PMID- 26538294 TI - Erratum: A trapped-ion-based quantum byte with 10(-5) next-neighbour cross-talk. PMID- 26538295 TI - Influence of Klotho gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease. AB - Klotho protein has been associated with beneficial effects that contribute to the maintenance of cardiovascular health. Diverse studies suggest that alterations in the levels of this molecule may be associated with pathophysiological abnormalities that result in increased cardiovascular risk. The primary aim of this proof-of-concept study was to analyse the existence of a potential link between Klotho gene polymorphisms and the expression level of this gene in the vascular wall, and additionally with the incidence of cardiovascular disease and cardiovascular risk factors. Our results indicate that the variant G-395A, located in the promoter region, influences Klotho gene vascular expression and is associated with the incidence of diabetes. Similarly, the exonic variant KL-VS was associated with the incidence of atherosclerotic vascular disease and coronary artery disease. Moreover, vascular expression levels of Klotho were related with the incidence of diabetes mellitus and coronary artery disease. These findings, which need to be confirmed in larger studies, suggest a potential role of Klotho in the pathogenesis of vascular damage. PMID- 26538296 TI - MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK. AB - The chemotactic migration of mesenchymal stem cells (MSCs) is fundamental for their use in cell-based therapies, but little is known about the molecular mechanisms that regulate their directed migration. MicroRNAs (miRNAs) participate in the regulation of a large variety of cellular processes. However, their roles in regulating the responses of MSCs to hepatocyte growth factor (HGF) remain elusive. Here, we found that microRNA-221 (miR-221) and microRNA-26b (miR-26b) were upregulated in MSCs subjected to HGF. Overexpression of miR-221 or miR-26b enhanced MSC migration through activation of PI3K/Akt signaling. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) was identified as a potential target of miR-221 and miR-26b; overexpression of miR-221 or miR-26b decreased PTEN expression at both mRNA and protein levels. Overexpression of miR-221 or miR 26b in MSCs increased the phosphorylation of focal adhesion kinase (FAK), a downstream effector of PTEN, which regulates cell migration through assembly and distribution of focal adhesions (FAs), and more dot-like FAs were localized at the periphery of these cells. Altering miR-221 or miR-26b expression influenced the directed migration of MSCs toward HGF. Inhibition of miR-221 or miR-26b suppressed the phosphorylation of Akt and FAK and upregulated PTEN expression, which was partly restored by HGF treatment. Collectively, these results demonstrate that miR-221 and miR-26b participate in regulating the chemotactic response of MSCs toward HGF. PMID- 26538297 TI - Risk of atrial fibrillation with bisphosphonate treatment. PMID- 26538298 TI - Nutrition-adaptive control of multiple-bacteriocin production by Weissella hellenica QU 13. AB - AIM: To analyse nutrition-adaptive multiple-bacteriocin production by Weissella hellenica QU 13. METHODS AND RESULTS: Weissella hellenica QU 13 produces two leaderless bacteriocins, weissellicins Y and M. Their production was studied in MRS and APT media by quantification analyses with liquid chromatography mass spectrometry (LC/MS), while transcriptional analysis of biosynthetic genes was performed by real-time reverse transcription (RT)-PCR. Weissellicin Y production was higher in MRS culture than in APT culture, while weissellicin M production was higher in APT culture than in MRS culture. APT medium contains a higher amount of thiamine than MRS medium, to enhance the growth of heterofermentative lactic acid bacteria. Therefore, thiamine addition to MRS culture enhanced the growth of W. hellenica QU 13; consequently, weissellicin Y production was decreased, while weissellicin M production was not affected. Furthermore, real time RT-PCR analyses indicated that the transcriptional trends of their respective structural genes, welY and welM, were different from each other, and that these two genes' transcriptions responded to nutrition conditions. CONCLUSION: Weissella hellenica QU 13 was demonstrated to control weissellicins Y and M production based on nutrition conditions. In addition, differential expression behaviour of weissellicins Y and M indicates that each of them would have separate roles to adapt to different environmental situations. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that describes nutrition adaptive multiple-bacteriocin production, in which thiamine inhibits bacteriocin production while it enhances the growth of the producer strain. PMID- 26538299 TI - Reply. PMID- 26538300 TI - Evaluation of apically extruded debris during root canal preparation in primary molar teeth using three different rotary systems and hand files. AB - AIM: To assess the amount of debris extruded apically during root canal preparation using various nickel titanium instrumentation systems and hand files in primary molar teeth. DESIGN: Sixty extracted primary first mandibular molar human teeth were randomly assigned to four groups (n = 15 teeth for each group). The canals were then instrumented with the following instrument systems: Revo-S, Mtwo, ProTaper Next, and hand files. Apically extruded debris during instrumentation was collected into pre-weighed Eppendorf tubes. The Eppendorf tubes were then stored in an incubator at 70 degrees C for 5 days. The weight of the dry extruded debris was established by subtracting the pre-instrumentation and post-instrumentation weight of the Eppendorf tubes for each group. The data were analyzed using one-way analysis of variance (anova) and Tukey's post hoc tests. RESULTS: ProTaper Next files were associated with less apically extruded debris than the Mtwo, Revo-S, and hand files (P < 0.05). Hand files extruded more debris than Mtwo and Revo-S instruments (P < 0.05), but there was no significant difference found between the Mtwo and Revo-S instruments (P > 0.05). CONCLUSIONS: All instruments were associated with apical extrusion of debris. ProTaper Next files caused less debris extrusion compared to the other systems used. PMID- 26538301 TI - Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins. AB - AIMS: A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain. METHODS: Using antibodies to poly-GA, poly-GP, poly-GR, poly-AP and poly-PR proteins, we examined sections of cerebral cortex, hippocampus, thalamus, cerebellum and spinal cord, from 20 patients with bvFTD and/or MND bearing an expansion in C9orf72 for aggregated deposits of dipeptide repeat proteins (DPR). RESULTS: Antibodies to poly-GA, poly-GP and poly-GR detected numerous rounded cytoplasmic inclusions (NCI) within granule cells of hippocampal dentate gyrus and those of the cerebellum, as well as 'star-burst' shaped NCI in pyramidal neurones of CA3/4 region of hippocampus. NCI were uncommon in Purkinje cells, and only very rarely seen in anterior horn cells. Poly-PA antibody detected occasional NCI within CA3/4 neurones alone, whereas poly-PR antibody did not identify any NCI but immunostained the nucleus of anterior horn cells, CA3/4 neurones and Purkinje cells, in patients with or without expansion in C9orf72, as well as in normal controls. Poly-GA antibody generally detected more DPR than poly-GP, which in turn was greater than poly-GR. All patients with bvFTD + MND or MND showed plentiful p62/TDP-43 positive inclusions in remaining anterior horn cells. CONCLUSION: Degeneration and loss of anterior horn cells associated with expansions in C9orf72 occurs in the absence of DPR, and implies that changes involving loss of nuclear staining for and a cytoplasmic aggregation of TDP-43 are more likely to be the cause of this. PMID- 26538302 TI - Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent. AB - Dominantly inherited ataxias (spinocerebellar ataxias, SCAs) are a genetically heterogeneous group of neurologic diseases characterized by progressive cerebellar and spinal tract degeneration with ataxia and other signs, common to all known subtypes. Several types are relatively frequent worldwide, but in several countries, one specific SCA may show a higher prevalence owing to founder phenomena. In Venezuela, genetic epidemiological features of SCAs have been assessed during the last 30 years; mutations in ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), ATXN8 (SCA8), ATXN10 (SCA10), TBP (SCA17) and ATN1 (dentatorubral pallidoluysian atrophy, DRPLA) loci were searched among 115 independent families. SCA7 was the most frequent subtype (26.6%), followed by SCA3 (25.0%), SCA2 (21.9%), SCA1 (17.2%), SCA10 (4.7%) and DRPLA (3.1%); in 43% of the families, the subtype remained unidentified. SCA7 mutations displayed strong geographic aggregation in two independent founder foci, and SCA1 showed a very remote founder effect for a subset of families. SCA10 families were scattered across the country, but all had an identical in-phase haplotype carried also by Mexican, Brazilian and Sioux patients, supporting a very old common Amerindian origin. Prevalence for dominant SCAs in Venezuela was estimated as 1:25 000 nuclear families, provenances of which are either Caucasoid, African or Amerindian. PMID- 26538303 TI - Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families. AB - Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder characterized by bone fragility. It is one of the rare forms of skeletal deformity caused by sequence variants in at least 14 different genes, including FKBP10 (MIM 607063) encoding protein FKBP65. Here we present three consanguineous families of Pakistani origin segregating OI in an autosomal recessive pattern. Genotyping using either single-nucleotide polymorphism markers by Affymetrix GeneChip Human Mapping 250K Nsp array or polymorphic microsatellite markers revealed a homozygous region, containing a candidate gene FKBP10, among affected members on chromosome 17q21.2. Sequencing the FKBP10 gene revealed a homozygous novel nonsense variant (c.1490G>A, p.Trp497*) in the family A and two previously reported variants, including a missense (c.344G>A, p.Arg115Gln), in the family B and duplication of a nucleotide C (c.831dupC, p.Gly278ArgfsX295) in the family C. Our findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system. PMID- 26538304 TI - Cerebellar vermis hypoplasia in CHARGE syndrome: clinical and molecular characterization of 18 unrelated Korean patients. AB - CHARGE syndrome (OMIM 214800) is a rare autosomal-dominant congenital malformation syndrome that results from haploinsufficiency of the chromodomain helicase DNA-binding protein 7 (CHD7). We performed a phenotypic characterization and genetic analysis of CHD7 in 18 Korean patients with CHARGE syndrome. Eighteen unrelated Korean patients (10 females and 8 males; age range 0.0-19.6 years) with CHARGE syndrome were enrolled. Clinical data were collected by retrospective review of medical records. A serial analysis via sequencing and multiple ligation dependent probe amplification of CHD7 was performed to determine the molecular genetic spectrum of the patients. The prevalence of cardinal symptoms was as follows: coloboma (13/18, 72.2%), heart defects (13/18, 72.2%), choanal atresia/stenosis (4/18, 22.2%), retarded growth (10/18, 55.6%), genital anomalies (15/18, 83.3%) and ear abnormalities (18/18, 100%). Five patients had cerebellar vermis hypoplasia (5/17, 29.4%) with no clinical symptoms or signs of cerebellar dysfunction. Furthermore, we identified genetic alterations in all 18 patients, including 10 novel mutations. Considering its frequency among patients with CHD7 mutations, cerebellar vermis hypoplasia may be a clinical diagnostic clue of CHARGE syndrome, although it is not included in the diagnostic criteria. And, the identification of CHD7 mutations may help the confirmative diagnosis. PMID- 26538305 TI - Resting metabolic rate varies by race and by sleep duration. AB - OBJECTIVE: Short sleep duration is a significant risk factor for weight gain, particularly in African Americans and men. Increased caloric intake underlies this relationship, but it remains unclear whether decreased energy expenditure is a contributory factor. The current study assessed the impact of sleep restriction and recovery sleep on energy expenditure in African American and Caucasian men and women. METHODS: Healthy adults participated in a controlled laboratory study. After two baseline sleep nights, subjects were randomized to an experimental (n = 36; 4 h sleep/night for five nights followed by one night with 12 h recovery sleep) or control condition (n = 11; 10 h sleep/night). Resting metabolic rate and respiratory quotient were measured using indirect calorimetry in the morning after overnight fasting. RESULTS: Resting metabolic rate-the largest component of energy expenditure-decreased after sleep restriction (-2.6%, P = 0.032) and returned to baseline levels after recovery sleep. No changes in resting metabolic rate were observed in control subjects. Relative to Caucasians (n = 14), African Americans (n = 22) exhibited comparable daily caloric intake but a lower resting metabolic rate (P = 0.043) and higher respiratory quotient (P = 0.013) regardless of sleep duration. CONCLUSIONS: Sleep restriction decreased morning resting metabolic rate in healthy adults, suggesting that sleep loss leads to metabolic changes aimed at conserving energy. PMID- 26538306 TI - Fizzy: feature subset selection for metagenomics. AB - BACKGROUND: Some of the current software tools for comparative metagenomics provide ecologists with the ability to investigate and explore bacterial communities using alpha- & beta-diversity. Feature subset selection--a sub-field of machine learning--can also provide a unique insight into the differences between metagenomic or 16S phenotypes. In particular, feature subset selection methods can obtain the operational taxonomic units (OTUs), or functional features, that have a high-level of influence on the condition being studied. For example, in a previous study we have used information-theoretic feature selection to understand the differences between protein family abundances that best discriminate between age groups in the human gut microbiome. RESULTS: We have developed a new Python command line tool, which is compatible with the widely adopted BIOM format, for microbial ecologists that implements information theoretic subset selection methods for biological data formats. We demonstrate the software tools capabilities on publicly available datasets. CONCLUSIONS: We have made the software implementation of Fizzy available to the public under the GNU GPL license. The standalone implementation can be found at http://github.com/EESI/Fizzy. PMID- 26538308 TI - Prolonged prone positioning under VV-ECMO is safe and improves oxygenation and respiratory compliance. AB - BACKGROUND: Data are sparse regarding the effects of prolonged prone positioning (PP) during VV-ECMO. Previous studies, using short sessions (<12 h), failed to find any effects on respiratory system compliance. In the present analysis, the effects of prolonged PP sessions (24 h) were retrospectively studied with regard to safety data, oxygenation and respiratory system compliance. METHODS: Retrospective review of 17 consecutive patients who required both VV-ECMO and prone positioning. PP under VV-ECMO was considered when the patient presented at least one unsuccessful ECMO weaning attempt after day 7 or refractory hypoxemia combined or not with persistent high plateau pressure. PP sessions had a duration of 24 h with fixed ECMO and respiratory settings. PP was not performed in patients under vasopressor treatment and in cases of recent open chest cardiac surgery. RESULTS: Despite optimized protective mechanical ventilation and other adjuvant treatment (i.e. PP, inhaled nitric oxide, recruitment maneuvers), 44 patients received VV-ECMO during the study period for refractory acute respiratory distress syndrome. Global survival rate was 66 %. Among the latter, 17 patients underwent PP during VV-ECMO for a total of 27 sessions. After 24 h in prone position, PaO2/FiO2 ratio significantly increased from 111 (84-128) to 173 (120-203) mmHg (p < 0.0001) while respiratory system compliance increased from 18 (12-36) to 32 (15-36) ml/cmH2O (p < 0.0001). Twenty-four hours after the return to supine position, tidal volume was increased from 3.0 (2.2-4.0) to 3.7 (2.8 5.0) ml/kg (p < 0.005). PaO2/FiO2 ratio increased by over 20 % in 14/14 sessions for late sessions (>=7 days) and in 7/13 sessions for early sessions (<7 days) (p = 0.01). Quantitative CT scan revealed a high percentage of non-aerated or poorly aerated lung parenchyma [52 % (41-62)] in all patients. No correlation was found between CT scan data and respiratory parameter changes. Hemodynamics did not vary and side effects were rare (one membrane thrombosis and one drop in ECMO blood flow). CONCLUSION: When used in combination with VV-ECMO, 24 h of prone positioning improves both oxygenation and respiratory system compliance. Moreover, our study confirms the absence of serious adverse events. PMID- 26538307 TI - Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast. AB - The budding yeast actin cables and contractile ring are important for polarized growth and division, revealing basic aspects of cytoskeletal function. To study these formin-nucleated structures, we built a three-dimensional (3D) computational model with actin filaments represented as beads connected by springs. Polymerization by formins at the bud tip and bud neck, crosslinking, severing, and myosin pulling, are included. Parameter values were estimated from prior experiments. The model generates actin cable structures and dynamics similar to those of wild type and formin deletion mutant cells. Simulations with increased polymerization rate result in long, wavy cables. Simulated pulling by type V myosin stretches actin cables. Increasing the affinity of actin filaments for the bud neck together with reduced myosin V pulling promotes the formation of a bundle of antiparallel filaments at the bud neck, which we suggest as a model for the assembly of actin filaments to the contractile ring. PMID- 26538309 TI - Influence of in-line microfilters on systemic inflammation in adult critically ill patients: a prospective, randomized, controlled open-label trial. AB - BACKGROUND: In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults. METHODS: In this prospective, randomized, controlled open-label study, we evaluated the influence of in-line microfilters on systemic immune activation in 504 critically ill adults with a central venous catheter in place and an expected length of stay in the intensive care unit >24 h. Patients were randomized to have in-line microfilters placed into all intravenous lines (intervention group) or usual care (control group). The primary endpoint was the number of intensive care unit days with SIRS. Secondary endpoints were the incidence of SIRS, SIRS criteria per day, duration of invasive mechanical ventilation, intensive care unit length of stay, the incidence of acute lung injury, maximum C-reactive protein, maximum white blood cell count, incidence of new candida and/or central-line-associated bloodstream infections, incidence of new thromboembolic complications, cumulative insulin requirements and presence of hyper- or hypoglycemia. RESULTS: The study groups did not differ in any baseline variable. There was no difference in the number of days in the intensive care unit with SIRS between microfilter and control patients [2 (0.8-4.7) vs. 1.8 (0.7-4.4), p = 0.62]. Except for a higher incidence of SIRS in microfilter patients (99.6 vs. 96.8 %, p = 0.04), no difference between the groups was observed in any secondary outcome parameter. Results did not change when only patients with an intensive care unit length of stay of greater than 7 days were included in the analysis. The rate of adverse events was comparable between microfilter and control patients. In two patients allocated to the microfilter group, the study intervention was discontinued for technical reasons. Use of in-line microfilters was associated with additional costs. CONCLUSIONS: The use of in-line microfilters failed to modulate systemic inflammation and clinical outcome parameters in critically ill adults. TRIAL REGISTRATION: Clinical Trials NCT01534390. PMID- 26538311 TI - Anaphylactic Shock at the Beginning of Hemodialysis. AB - In patients who receive hemodialysis, most hypersensitivity reactions to components of the dialysis circuit are due to ethylene oxide or complement activating bio-incompatible membranes. We present a case of a 59 year-old female, with a 4-year history of uneventful hemodialysis using a cellulose based dialyzer membrane at her outpatient dialysis center, who developed repeated anaphylactic reactions associated with markers of an IgE mediated hypersensitivity reaction when a polysulfone based dialyzer membrane was used while she was hospitalized. Only when the patient's dialyzer was changed back to her usual cellulose based membrane, did these reactions cease. On the basis of her clinical course and laboratory findings, we concluded that the patient's symptoms were due to exposure to polysulfone. This case reminds us that "biocompatible" membranes are not free from dialyzer reactions, and can be especially severe if the mechanism is an IgE mediated anaphylactic hypersensitivity reaction. PMID- 26538310 TI - Arginase 1+ microglia reduce Abeta plaque deposition during IL-1beta-dependent neuroinflammation. AB - BACKGROUND: Neuroinflammation has long been considered a driver of Alzheimer's disease progression. However, experiments developed to explore the interaction between neuroinflammation and Alzheimer's disease (AD) pathology showed a surprising reduction in amyloid beta (Abeta) plaque deposition. We sought to understand this unexpected outcome by examining microglia phenotypes during chronic neuroinflammation. METHODS: Using an adeno-associated virus vector carrying hIL-1beta cDNA, inflammation was induced in one hippocampus of 8-month old amyloid precursor protein (APP)/PS1 mice for 4 weeks, while the other hemisphere received control injections. Bone marrow chimeras and staining analysis were used to identify the origins and types of immune cells present during sustained inflammation. Arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS) immunoreactivity were used as markers of alternatively activated and classically activated cells, respectively, and changes in cellular uptake of Abeta by Arg1+ or iNOS+ microglia was demonstrated by confocal microscopy. To determine if an anti-inflammatory phenotype was present during neuroinflammation, RNA was extracted on flow-sorted microglia and rt-PCR was performed. Interleukin 4 injection was used to induce alternatively activated cells, whereas a minipump and intrahippocampal cannula was used to deliver an interleukin (IL)-4Ralpha antibody to block the induction of Arg1+ cells in the setting of sustained IL 1beta expression. RESULTS: We observed a robust upregulation of centrally derived Arg1+ microglia present only in the inflamed hemisphere. Furthermore, in the inflamed hemisphere, greater numbers of Arg1+ microglia contained Abeta when compared to iNOS+ microglia. RNA isolated from flow-sorted microglia from the inflamed hemisphere demonstrated elevation of mRNA species consistent with alternative activation as well as neuroprotective genes such as BDNF and IGF1. To explore if Arg1+ microglia mediated plaque reduction, we induced Arg1+ microglia with IL-4 and observed significant plaque clearance. Moreover, when we reduced Arg1+ microglia induction in the context of neuroinflammation using an anti-IL 4Ralpha antibody delivered via intrahippocampal cannula, we observed a clear correlation between numbers of Arg1+ microglia and plaque reduction. CONCLUSIONS: Together, these findings suggest that Arg1+ microglia are involved in Abeta plaque reduction during sustained, IL-1beta-dependent neuroinflammation, opening up possible new avenues for immunomodulatory therapy of AD. PMID- 26538312 TI - Interplay between solid state transitions, conductivity mechanisms, and electrical relaxations in a [PVBTMA] [Br]-b-PMB diblock copolymer membrane for electrochemical applications. AB - Understanding the structure-property relationships and the phenomena responsible for ion conduction is one of the keys in the design of novel ionomers with improved properties. In this report, the morphology and the mechanism of ion exchange in a model anion exchange membrane (AEM), poly(vinyl benzyl trimethyl ammonium bromide)-block-poly(methylbutylene) ([PVBTMA][Br]-b-PMB), is investigated with small angle X-ray scattering, high-resolution thermogravimetry, modulated differential scanning calorimetry, dynamic mechanical analysis, and broadband electrical spectroscopy. The hyper-morphology of the material consists of hydrophilic domains characterized by stacked sides of [PVBTMA][Br] which are sandwiched between "spaghetti-like" hydrophobic cylindrical parallel domains of the PMB block. The most important interactions in the hydrophilic domains occur between the dipoles of ammonium bromide ion pairs in the side chains of adjacent chains. A reordering of the ion pair dipoles is responsible for a disorder-order transition (Tdelta) at high temperature, observed here for the first time in AEMs, which results in a dramatic decrease of the ionic conductivity. The overall mechanism of long range charge transfer, deduced from a congruent picture of all of the results, involves two distinct ion conduction pathways. In these pathways, hydration and the motion of the ionic side groups are crucial to the conductivity of the AEM. Unlike the typical perfluorinated sulfonated proton-conducting polymer, the segmental motion of the backbone is negligible. PMID- 26538313 TI - Fitting Transporter Activities to Cellular Drug Concentrations and Fluxes: Why the Bumblebee Can Fly. AB - A recent paper in this journal argued that reported expression levels, kcat and Km for drug transporters could be used to estimate the likelihood that drug fluxes through Caco-2 cells could be accounted for solely by protein transporters. It was in fact concluded that if five such transporters contributed 'randomly' they could account for the flux of the most permeable drug tested (verapamil) 35% of the time. However, the values of permeability cited for verapamil were unusually high; this and other drugs have much lower permeabilities. Even for the claimed permeabilities, we found that a single 'random' transporter could account for the flux 42% of the time, and that two transporters can achieve 10.10(-6)cm.s(-1) 90% of the time. Parameter optimisation methods show that even a single transporter can account for Caco-2 drug uptake of the most permeable drug. Overall, the proposal that 'phospholipid bilayer diffusion (of drugs) is negligible' is not disproved by the calculations of 'likely' transporter-based fluxes. PMID- 26538315 TI - Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism. AB - Sirtuins are an evolutionarily conserved family of NAD(+)-dependent deacylases that display diversity in subcellular localization and function. SIRT2, the predominantly cytosolic sirtuin, is among the least understood of the seven mammalian sirtuin isoforms described (SIRT1-7). The purpose of this review is to summarize the most recent findings about the potential roles and effects of SIRT2 in mammalian metabolic homeostasis. We discuss the different functions and targets of SIRT2 in various physiological processes, including adipogenesis, fatty acid oxidation, gluconeogenesis, and insulin sensitivity. We also cover the role of SIRT2 in inflammation and oxidative stress due to the possible implications for metabolic disorders. Finally, we consider its potential as a therapeutic target for the prevention and treatment of type 2 diabetes. PMID- 26538314 TI - Lessons from Hot Spot Analysis for Fragment-Based Drug Discovery. AB - Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high affinity, drug-like ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from a protein 3D structure, and how their strength, number, and spatial arrangement govern the potential for a surface site to bind to fragment sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery. PMID- 26538316 TI - Targeted Therapies for Triple-Negative Breast Cancer: Combating a Stubborn Disease. AB - Triple-negative breast cancers (TNBCs) constitute a heterogeneous subtype of breast cancers that have a poor clinical outcome. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets, with several candidate compounds having now entered clinical trials for TNBC patients. However, initial results remain modest, thereby highlighting challenges potentially involving intra- and intertumoral heterogeneity and acquisition of therapy resistance. We present a comprehensive review on emerging targeted therapies for treating TNBCs, including the promising approach of immunotherapy and the prognostic value of tumor-infiltrating lymphocytes. We discuss the impact of pathway rewiring in the acquisition of drug resistance, and the prospect of employing combination therapy strategies to overcome challenges towards identifying clinically-viable targeted treatment options for TNBC. PMID- 26538317 TI - NAMPT as a Therapeutic Target against Stroke. AB - Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide (NMN) and then to maintain homeostasis of nicotinamide adenine dinucleotide (NAD), which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin (SIRT) signaling, constituting a strong intrinsic defense system against various stresses. Most recently, studies have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these benefits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators, and ischemic conditioning are promising for stroke salvage and rehabilitation. This review discusses the current NAMPT data in the context of translational efforts for stroke treatment. PMID- 26538318 TI - Advances in Computational Techniques to Study GPCR-Ligand Recognition. AB - G-protein-coupled receptors (GPCRs) are among the most intensely investigated drug targets. The recent revolutions in protein engineering and molecular modeling algorithms have overturned the research paradigm in the GPCR field. While the numerous ligand-bound X-ray structures determined have provided invaluable insights into GPCR structure and function, the development of algorithms exploiting graphics processing units (GPUs) has made the simulation of GPCRs in explicit lipid-water environments feasible within reasonable computation times. In this review we present a survey of the recent advances in structure based drug design approaches with a particular emphasis on the elucidation of the ligand recognition process in class A GPCRs by means of membrane molecular dynamics (MD) simulations. PMID- 26538319 TI - Pharmacokinetics of procaterol in thoroughbred horses. AB - Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 MUg/kg) and oral (2.0 MUg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 +/- 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 +/- 0.23 L/kg, and the elimination half-life was 2.85 +/- 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses. PMID- 26538320 TI - Exceptionally Inert Lanthanide(III) PARACEST MRI Contrast Agents Based on an 18 Membered Macrocyclic Platform. AB - We report a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6) dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L(1)) that forms extraordinary inert complexes with Ln(3+) ions. The [EuL(1)](3+) complex does not undergo dissociation in 1 M HCl over a period of months at room temperature. Furthermore, high concentrations of phosphate and Zn(2+) ions at room temperature do not provoke metal-complex dissociation. The X ray crystal structures of six Ln(3+) complexes reveal ten coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and the four oxygen atoms of the hydroxyethyl pendant arms. The analysis of the Yb(3+)- and Pr(3+)-induced paramagnetic (1)H NMR shifts show that the solid-state structures are retained in aqueous solution. The intensity of the (1)H NMR signal of bulk water can be modulated by saturation of the signals of the hydroxy protons of Pr(3+), Eu(3+), and Yb(3+) complexes following chemical-exchange saturation transfer (CEST). The ability of these complexes to provide large CEST effects at 25 and 37 degrees C and pH 7.4 was confirmed by using CEST magnetic resonance imaging experiments. PMID- 26538321 TI - Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products. AB - Covering: up to 2015. Over the centuries, microbial secondary metabolites have played a central role in the treatment of human diseases and have revolutionised the pharmaceutical industry. With the increasing number of sequenced microbial genomes revealing a plethora of novel biosynthetic genes, natural product drug discovery is entering an exciting second golden age. Here, we provide a concise overview as an introductory guide to the main methods employed to unlock or up regulate these so called 'cryptic', 'silent' and 'orphan' gene clusters, and increase the production of the encoded natural product. With a predominant focus on bacterial natural products we will discuss the importance of the bioinformatics approach for genome mining, the use of first different and simple culturing techniques and then the application of genetic engineering to unlock the microbial treasure trove. PMID- 26538323 TI - Reproducibility blues. AB - Research findings advance science only if they are significant, reliable and reproducible. Scientists and journals must publish robust data in a way that renders it optimally reproducible. Reproducibility has to be incentivized and supported by the research infrastructure but without dampening innovation. PMID- 26538322 TI - Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. AB - In Alzheimer's disease and tauopathies, tau protein aggregates into neurofibrillary tangles that progressively spread to synaptically connected brain regions. A prion-like mechanism has been suggested: misfolded tau propagating through the brain seeds neurotoxic aggregation of soluble tau in recipient neurons. We use transgenic mice and viral tau expression to test the hypotheses that trans-synaptic tau propagation, aggregation, and toxicity rely on the presence of endogenous soluble tau. Surprisingly, mice expressing human P301Ltau in the entorhinal cortex showed equivalent tau propagation and accumulation in recipient neurons even in the absence of endogenous tau. We then tested whether the lack of endogenous tau protects against misfolded tau aggregation and toxicity, a second prion model paradigm for tau, using P301Ltau-overexpressing mice with severe tangle pathology and neurodegeneration. Crossed onto tau-null background, these mice had similar tangle numbers but were protected against neurotoxicity. Therefore, misfolded tau can propagate across neural systems without requisite templated misfolding, but the absence of endogenous tau markedly blunts toxicity. These results show that tau does not strictly classify as a prion protein. PMID- 26538324 TI - Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology. AB - Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-alpha-acetyl-l arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population. PMID- 26538325 TI - Monomorphic ventricular tachycardia in patients with Brugada syndrome: A multicenter retrospective study. AB - BACKGROUND: Isolated cases of monomorphic ventricular tachycardia (MVT) in patients with Brugada syndrome (BrS) have been reported. OBJECTIVE: We aimed to describe the incidence and characteristics of MVT in a cohort of patients with BrS who had received an implantable cardioverter-defibrillator (ICD). METHODS: Data from 834 patients with BrS implanted with an ICD in 15 tertiary hospitals between 1993 and 2014 were included. RESULTS: The mean age of enrolled patients was 45.3 +/- 13.9 years; 200 patients (24%) were women. During a mean follow-up of 69.4 +/- 54.3 months, 114 patients (13.7%) experienced at least 1 appropriate ICD intervention, with MVT recorded in 35 patients (4.2%) (sensitive to antitachycardia pacing in 15 [42.8%]). Only QRS width was an independent predictor of MVT in the overall population. Specifically, 6 (17.1%) patients presented with right ventricular outflow tract tachycardia (successfully ablated from the endocardium in 4 and epicardial and endocardial ablation in 1), 2 patients with MVT arising from the left ventricle (1 successfully ablated in the supra lateral mitral annulus), and 2 (5.7%) patients with bundle branch reentry ventricular tachycardia. Significant structural heart disease was ruled out by echocardiography and/or cardiac magnetic resonance imaging. CONCLUSION: In this retrospective study, 4.2% of patients with BrS implanted with an ICD presented with MVT confirmed as arising from the right ventricular outflow tract tachycardia in 6, patients with MVT arising from the left ventricle in 2, and patients with bundle branch reentry ventricular tachycardia in 2. Endocardial and/or epicardial ablation was successful in 80% of these cases. These data imply that the occurrence of MVT should not rule out the possibility of BrS. This finding may also be relevant for ICD model selection and programming. PMID- 26538327 TI - A Hierarchical Multiple-Level Approach to the Assessment of Interpersonal Relatedness and Self-Definition: Implications for Research, Clinical Practice, and DSM Planning. AB - Extant research suggests there is considerable overlap between so-called 2 polarities models of personality development; that is, models that propose that personality development evolves through a dialectic synergistic interaction between 2 key developmental tasks across the life span-the development of self definition on the one hand and of relatedness on the other. These models have attracted considerable research attention and play a central role in DSM planning. This article provides a researcher- and clinician-friendly guide to the assessment of these personality theories. We argue that current theoretical models focus on issues of relatedness and self-definition at different hierarchically organized levels of analysis; that is (a) at the level of broad personality features, (b) at the motivational level (i.e., the motivational processes underlying the development of these dimensions), and (c) at the level of underlying internal working models or cognitive affective schemas, and the specific interpersonal features and problems in which they are expressed. Implications for further research and DSM planning are outlined. PMID- 26538328 TI - Electrochemical Synthesis of Photoelectrodes and Catalysts for Use in Solar Water Splitting. AB - This review focuses on introducing and explaining electrodepostion mechanisms and electrodeposition-based synthesis strategies used for the production of catalysts and semiconductor electrodes for use in water-splitting photoelectrochemical cells (PECs). It is composed of three main sections: electrochemical synthesis of hydrogen evolution catalysts, oxygen evolution catalysts, and semiconductor electrodes. The semiconductor section is divided into two parts: photoanodes and photocathodes. Photoanodes include n-type semiconductor electrodes that can perform water oxidation to O2 using photogenerated holes, while photocathodes include p-type semiconductor electrodes that can reduce water to H2 using photoexcited electrons. For each material type, deposition mechanisms were reviewed first followed by a brief discussion on its properties relevant to electrochemical and photoelectrochemical water splitting. Electrodeposition or electrochemical synthesis is an ideal method to produce individual components and integrated systems for PECs due to its various intrinsic advantages. This review will serve as a good resource or guideline for researchers who are currently utilizing electrochemical synthesis as well as for those who are interested in beginning to employ electrochemical synthesis for the construction of more efficient PECs. PMID- 26538326 TI - JPH-2 interacts with Cai-handling proteins and ion channels in dyads: Contribution to premature ventricular contraction-induced cardiomyopathy. AB - BACKGROUND: In a canine model of premature ventricular contraction-induced cardiomyopathy (PVC-CM), Cav1.2 is downregulated and misplaced from transverse tubules (T tubules). Junctophilin-2 (JPH-2) is also downregulated. OBJECTIVES: The objectives of this study were to understand the role of JPH-2 in PVC-CM and to probe changes in other proteins involved in dyad structure and function. METHODS: We quantify T-tubule contents (di-8-ANEPPS fluorescence in live myocytes), examine myocyte ultrastructures (electron microscopy), probe JPH-2 interacting proteins (co-immunoprecipitation), quantify dyad and nondyad protein levels (immunoblotting), and examine subcellular distributions of dyad proteins (immunofluorescence/confocal microscopy). We also test direct JPH-2 modulation of channel function (vs indirect modulation through dyad formation) using heterologous expression. RESULTS: PVC myocytes have reduced T-tubule contents but otherwise normal ultrastructures. Among 19 proteins examined, only JPH-2, bridging integrator-1 (BIN-1), and Cav1.2 are highly downregulated in PVC hearts. However, statistical analysis indicates a general reduction in dyad protein levels when JPH-2 is downregulated. Furthermore, several dyad proteins, including Na/Ca exchanger, are missing or shifted from dyads to the peripheral surface in PVC myocytes. JPH-2 directly or indirectly interacts with Cai-handling proteins, Cav1.2 and KCNQ1, although not BIN-1 or other scaffolding proteins tested. Expression in mammalian cells that do not have dyads confirms direct JPH-2 modulation of the L-type Ca channel current (Cav1.2/voltage-gated Ca channel beta subunit 2) and slow delayed rectifier current (KCNQ1/KCNE1). CONCLUSION: JPH-2 is more than a "dyad glue": it can modulate Cai handling and ion channel function in the dyad region. Downregulation of JPH-2, BIN-1, and Cav1.2 plays a deterministic role in PVC-CM. Dissecting the hierarchical relationship among the three is necessary for the design of therapeutic interventions to prevent the progression of PVC-CM. PMID- 26538329 TI - Differences in forward angular light scattering distributions between M1 and M2 macrophages. AB - The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture. PMID- 26538330 TI - Chlorophyll a fluorescence lifetime reveals reversible UV-induced photosynthetic activity in the green algae Tetraselmis. AB - The fluorescence lifetime is a very useful parameter for investigating biological materials on the molecular level as it is mostly independent of the fluorophore concentration. The green alga Tetraselmis blooms in summer, and therefore its response to UV irradiation is of particular interest. In vivo fluorescence lifetimes of chlorophyll a were measured under both normal and UV-stressed conditions of Tetraselmis. Fluorescence was induced by two-photon excitation using a femtosecond laser and laser scanning microscope. The lifetimes were measured in the time domain by time-correlated single-photon counting. Under normal conditions, the fluorescence lifetime was 262 ps, while after 2 h of exposure to UV radiation the lifetime increased to 389 ps, indicating decreased photochemical quenching, likely caused by a damaged and down-regulated photosynthetic apparatus. This was supported by a similar increase in the lifetime to 425 ps when inhibiting photosynthesis chemically using DCMU. Furthermore, the UV-stressed sample was dark-adapted overnight, resulting in a return of the lifetime to 280 ps, revealing that the damage caused by UV radiation is repairable on a relatively short time scale. This reversal of photosynthetic activity was also confirmed by [Formula: see text] measurements. PMID- 26538331 TI - Discrimination between conformational selection and induced fit protein-ligand binding using Integrated Global Fit analysis. AB - Molecular recognition between proteins and small molecule ligands is at the heart of biological function in cellular systems and the basis of modern rational drug development. Therefore, the mechanisms governing protein-ligand interaction have been objects of research for many decades. The last 15 years has seen a revival of a discussion whether conformational selection (CS) or induced fit (IF) is the most relevant binding mechanism. A decreasing observed rate constant, k obs, with increasing ligand concentration was considered to be a hallmark of CS, but according to contemporary knowledge, a positive saturating behavior of k obs can be explained by both CS and IF mechanisms. The only currently recognized kinetic method to differentiate between both binding mechanisms includes the measurement of two separate series of binding kinetics with variation of either protein or ligand under pseudo-first-order conditions. This study avoids the disadvantage of high protein concentrations and provides evidence that a comprehensive Integrated Global Fit analysis of sets of binding kinetics with just varied ligand concentration in combination with equilibrium data and optional displacement kinetics can effectively differentiate between CS and IF binding mechanisms. The limiting situation, when physical binding dominates over the previous (CS) or subsequent (IF) conformational changes, is carefully analyzed. Finally, the relevance of kinetic methods and the elucidation of more complex binding mechanisms are discussed for advanced rational selection and optimization of drug candidates. PMID- 26538332 TI - Dividing organelle tracks into Brownian and motor-driven intervals by variational maximization of the Bayesian evidence. AB - Many organelles and vesicles in live cells move in a start-stop manner when observed for ~10 s by optical microscopy. Changes in velocity and directional persistence of such particles are a potentially rich source of insight into the mechanisms leading to the start and stop states. Unbiased assessment of the most probable number of states, the properties of each state, and the most probable state for the particle at each moment can be accomplished by variational Bayesian methods combined with a hidden Markov model and a Gaussian mixture model. Our track analysis method, "vbTRACK", applied this combination of methods to particle velocity v or changes in the direction of travel evaluated from simulated tracks and from tracks of peroxisomes in live cells. When tested with numerical data, vbTRACK reliably determined the number of states, the mean and variance of the velocity or the direction of travel for each state, and the most probable state during each frame. When applied to the tracks of peroxisomes in live cells, some tracks separated into two states, one with high velocity and directionality, the other approximately Brownian. Other tracks of particles in live cells separated into several diffusive states with distinct diffusion constants. PMID- 26538333 TI - Extractable and non-extractable polyphenols from blueberries modulate LPS-induced expression of iNOS and COX-2 in RAW264.7 macrophages via the NF-kappaB signalling pathway. AB - BACKGROUND: Plant polyphenols are rich in blueberries that have a wide range of properties beneficial to human health. There are two types, according to the solubility of polyphenols, which were defined as extractable polyphenols (EPP) and non-extractable polyphenols (NEPP), respectively. At present, in most of reports, 'total polyphenol' refers only to EPP excluding NEPP. In this paper, the effects of EPP and NEPP on lipopolysaccharides (LPS) induced production of nitric oxide (NO) and gene expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW264.7 cells via nuclear factor-kappaB (NF-kappaB) signalling pathway were compared. RESULTS: The results showed that EPP and NEPP from blueberries significantly inhibited the LPS-induced production of NO and gene expression of iNOS and COX-2 in cells. The constitutive level of p65 sub-unit of NF-kappaB was obviously detected after the treatments with EPP or NEPP. By contrast, the level of phosphorylated p65 (P-p65) was strongly inhibited by EPP or NEPP. EPP had a stronger inhibition on the gene expression of iNOS and COX-2 than that of NEPP. CONCLUSION: These findings of inhibition of iNOS and COX-2 mRNA expression through the suppression of NF-kappaB suggest that EPP and ENPP from blueberries have significant anti-inflammatory effect and may be a potential medicine. (c) 2015 Society of Chemical Industry. PMID- 26538335 TI - Human T-Lymphotropic Virus Type 1 and 2 Seroprevalence among first-time blood donors in Chile, 2011-2013. AB - Infection with human T-lymphotropic virus type 1/2 (HTLV-1/2) is a major health problem. HTLV-1/2 infection is endemic in Chile but representative donor prevalence data are lacking. Data on all blood donors in a large network of Chilean blood centers were examined during 2011-2013. Screening of HTLV-1/2 antibodies were measured by enzyme immunoassay (EIA) at all blood banks. Blood samples with anticoagulants from initially reactive blood donors were analyzed by serological confirmation tests (immunofluorescence or recombinant immunoblot) at the HTLV National Reference Laboratory of the Public Health Institute of Chile. Additionally, detection of HTLV-1 and HTLV-2 provirus in peripheral blood mononuclear cells (PBMCs) was performed in all blood donors as confirmatory test. Prevalence rates were calculated. Among 694,016 donors, 706 were seropositive for HTLV-1 (prevalence, 1.02 cases per 1,000; 95% confidence interval [CI], 0.94 1.09), and 97 were seropositive for HTLV-2 (prevalence, 0.14 cases per 1,000; 95%CI, 0.11-0.17). Prevalence of HTLV-1 differed considerably by region, from 0.51 to 1.69 per 1,000. Prevalence of HTLV-2 was similar across the country (0.12 0.16). HTLV-1 prevalence was associated with female sex, older age, and residence in the north of Chile. HTVL-2 prevalence was associated with older age. The HTLV 1 prevalence among Chilean blood donors was relatively high and could be reduced by improving donor recruitment and selection in high prevalence areas. Blood center data may contribute to surveillance for HTLV-1 and HTLV-2 infections. PMID- 26538334 TI - Inhibition of actin polymerization in the NAc shell inhibits morphine-induced CPP by disrupting its reconsolidation. AB - Drug-associated contextual cues contribute to drug craving and relapse after abstinence, which is a major challenge to drug addiction treatment. Previous studies showed that disrupting memory reconsolidation impairs drug reward memory. However, the underlying mechanisms remain elusive. Although actin polymerization is involved in memory formation, its role in the reconsolidation of drug reward memory is unknown. In addition, the specific brain areas responsible for drug memory have not been fully identified. In the present study, we found that inhibiting actin polymerization in the nucleus accumbens (NAc) shell, but not the NAc core, abolishes morphine-induced conditioned place preference (CPP) by disrupting its reconsolidation in rats. Moreover, this effect persists for more than 2 weeks by a single injection of the actin polymerization inhibitor, which is not reversed by a morphine-priming injection. Furthermore, the application of actin polymerization inhibitor outside the reconsolidation window has no effect on morphine-associated contextual memory. Taken together, our findings first demonstrate that inhibiting actin polymerization erases morphine-induced CPP by disrupting its reconsolidation. Our study suggests that inhibition of actin polymerization during drug memory reconsolidation may be a potential approach to prevent drug relapse. PMID- 26538336 TI - Body Morphology and Its Associations With Thoracolumbar Trauma Sustained in Motor Vehicle Collisions. AB - OBJECTIVE: This study investigates the relationship between body mass index (BMI) and the patterns of thoracolumbar spinal fractures sustained by patients in motor vehicle collisions (MVCs). DESIGN: The Crash Injury Research and Engineering Network (CIREN) database was used to analyze prospective data on patients involved in MVCs of moderate severity. METHODS: Thoracolumbar fractures in 631 subjects were analyzed for patient-, vehicle-, and crash-related factors. Spine injuries were classified according to a modified Denis classification system. Subjects were stratified into BMI subgroups that were then analyzed by injury level, fracture pattern, associated systemic injury, and mortality. RESULTS: Obesity (BMI >= 30.0) was found to be associated with a more cephalad level of injury. Mean BMI was higher in 67 patients with fatal outcomes compared with 557 survivors. Patients who sustained a thoracolumbar fracture and another system injury were more likely to be overweight and obese. Among the various fracture patterns analyzed, BMI was highest in patients with extension injuries. CONCLUSION: This study characterizes the relationship between body morphology and the thoracolumbar injury patterns associated with MVC to improve understanding of the overall morbidity and mortality of these injuries. These results corroborate research demonstrating the unique relationships between patients who are obese and specific patterns of injury and higher injury severity caused by MVCs and establish a rationale for specifically including thoracolumbar spine parameters in crash safety standards. PMID- 26538337 TI - Change of Leadership and New Ventures. PMID- 26538338 TI - Radiographic Stage Does Not Correlate With Symptom Severity in Thumb Basilar Joint Osteoarthritis. AB - BACKGROUND: We hypothesize that thumb basilar joint osteoarthritis (TBJA) radiographic stage does not correlate with patient-reported measures of symptom severity. METHODS: Patients with unilateral TBJA who completed the 11-item QuickDASH (Disabilities of the Arm, Shoulder, and Hand), Short-Form 12 Health Survey (SF-12) Mental Component and SF-12 Physical Component surveys were prospectively enrolled in the study. The Eaton-Littler radiographic stage was assigned for each patient. The correlation between the radiographic score and disease stage was calculated. RESULTS: Sixty-two patients (15 men, 47 women; average age, 62.3 years) formed the basis of this study. The average QuickDASH score (and standard deviation) for patients with stage 1 TBJA was 31.5 (11.4); for those with stage 2, it was 37.9 (17.4); with stage 3, it was 30.1 (13.0), and with stage 4, it was 39.4 (12.5). Eaton-Littler stage did not correlate significantly with QuickDASH scores (rho = -0.014, P = 0.91). Neither SF-12 Mental Component scores (MCS-12: rho = 0.019, P = 0.89) nor the SF-12 Physical Component scores (PCS-12: rho = 0.145, P = 0.26) correlated with TBJA stage. CONCLUSION: Radiographic severity in TBJA does not correlate with validated patient-reported symptom scores. Metrics that link radiographic and subjective components of TBJA may improve surgical decision making and monitoring of treatment response. LEVEL OF EVIDENCE: Prognostic, level II. PMID- 26538339 TI - Analysis of Adsorbate-Adsorbate and Adsorbate-Adsorbent Interactions to Decode Isosteric Heats of Gas Adsorption. AB - A qualitative interpretation is proposed to interpret isosteric heats of adsorption by considering contributions from three general classes of interaction energy: fluid-fluid heat, fluid-solid heat, and fluid-high-energy site (HES) heat. Multiple temperature adsorption isotherms are defined for nitrogen, T=(75, 77, 79) K, argon at T=(85, 87, 89) K, and for water and methanol at T=(278, 288, 298) K on a well-characterized polymer-based, activated carbon. Nitrogen and argon are subjected to isosteric heat analyses; their zero filling isosteric heats of adsorption are consistent with slit-pore, adsorption energy enhancement modelling. Water adsorbs entirely via specific interactions, offering decreasing isosteric heat at low pore filling followed by a constant heat slightly in excess of water condensation enthalpy, demonstrating the effects of micropores. Methanol offers both specific adsorption via the alcohol group and non-specific interactions via its methyl group; the isosteric heat increases at low pore filling, indicating the predominance of non-specific interactions. PMID- 26538340 TI - The Maintaining Factors of Social Anxiety: A Three-Group Comparison of a Clinical Sample with Highly Socially Anxious Students and Non-Anxious Students. AB - BACKGROUND: Clark and Wells' (1995) cognitive model of social anxiety (CWM) explains the maintenance of social anxiety and has been used as a guide for treatment of Social Anxiety Disorder (SAD). Few studies have examined the components of the model together across different samples. AIMS: This study had two distinct aims: to test the components of CWM and to examine how the variables of CWM may differ between clinical and non-clinical samples with varying levels of social anxiety. METHOD: Hypothesized relationships between three groups (i.e. a clinical sample of individuals diagnosed with SAD (ClinS), n = 40; socially anxious students (HSA), n = 40; and, non-anxious students (LSA), n = 40) were investigated. RESULTS: Four out of five CWM variables tested were able to distinguish between highly socially anxious and non-anxious groups after controlling for age and depression. CONCLUSIONS: CWM variables are able to distinguish between high and low levels of social anxiety and are uniquely related to social anxiety over depression. PMID- 26538342 TI - A data-driven approach to mapping cortical and subcortical intrinsic functional connectivity along the longitudinal hippocampal axis. AB - The hippocampus (HPC) is functionally heterogeneous along the longitudinal anterior-posterior axis. In rodent models, gene expression maps define at least three discrete longitudinal subregions, which also differ in function, and in anatomical connectivity with the rest of the brain. In humans, equivalent HPC subregions are less well defined, resulting in a lack of consensus in neuroimaging approaches that limits translational study. This study determined whether a data-driven analysis, namely independent component analysis (ICA), could reproducibly define human HPC subregions, and map their respective intrinsic functional connectivity (iFC) with the rest of the brain. Specifically, we performed ICA of resting-state fMRI activity spatially restricted within the HPC, to determine the configuration and reproducibility of functional HPC components. Using dual regression, we then performed multivariate analysis of iFC between resulting HPC components and the whole brain, including detailed connectivity with the hypothalamus, a functionally important connection not yet characterized in human. We found hippocampal ICA resulted in highly reproducible longitudinally discrete components, with greater functional heterogeneity in the anterior HPC, consistent with animal models. Anterior hippocampal components shared iFC with the amygdala, nucleus accumbens, medial prefrontal cortex, posterior cingulate cortex, midline thalamus, and periventricular hypothalamus, whereas posterior hippocampal components shared iFC with the anterior cingulate cortex, retrosplenial cortex, and mammillary bodies. We show that spatially masked hippocampal ICA with dual regression reproducibly identifies functional subregions in the human HPC, and maps their respective brain intrinsic connectivity. Hum Brain Mapp 37:462-476, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26538341 TI - The Course of Quality of Life in Patients on Peritoneal Dialysis: A 12-month Prospective Observational Cohort Study. AB - BACKGROUND: Quality of life (QOL) impairments are common in patients undergoing dialysis, and have been strongly associated with significant clinical outcomes like mortality and morbidity. Despite this, little is known about the course of QOL over time, especially for patients on peritoneal dialysis (PD). PURPOSE: This prospective study was set to explore course and determinants of QOL over 12 months in PD patients. METHODS: A total of 115 PD patients completed the SF-12 and Kidney Disease Quality of Life Short Form (KDQOL-SF) at baseline and 12 months later. Intra-individual changes in physical (physical component summary, PCS), mental (mental component summary, MCS), and Kidney Disease Component Summary scores (KDCS) were identified based on the minimally important clinical difference threshold. Clinical information was extracted from medical records. RESULTS: Of the patients, 74-80 % reported physical QOL impairments, as compared to 29-33 % who reported mental/emotional QOL impairments. PCS and MCS scores remained stable across 12 months. Significant deterioration was noted in the domains of patient satisfaction, staff encouragement, and social support, while there were significant increases in the perceived effects of kidney disease. Intra-individual trajectory analyses indicated that one in three patients reported deteriorating QOL. No sociodemographic or clinical variables were found to be associated with course of outcomes. CONCLUSIONS: Although PD offers the convenience of home-based care, it is associated with persisting QOL impairments and diminishing QOL over time, especially in domains related to quality of care and support. This highlights the need for improving or maintaining standards of care and support for PD patients as they become increasingly established on their regimes. PMID- 26538343 TI - Discussion of "Combining Health Data Uses to Ignite Health System Learning". AB - This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Combining Health Data Uses to Ignite Health System Learning" written by John D. Ainsworth and Iain E. Buchan [1]. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Ainsworth and Buchan. In subsequent issues the discussion can continue through letters to the editor. With these comments on the paper "Combining Health Data Uses to Ignite Health System Learning", written by John D. Ainsworth and Iain E. Buchan [1], the journal seeks to stimulate a broad discussion on new ways for combining data sources for the reuse of health data in order to identify new opportunities for health system learning. An international group of experts has been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper. PMID- 26538345 TI - Evaluation in health promotion: thoughts from inside a human research ethics committee. AB - Health promotion research, quality improvement and evaluation are all activities that raise ethical issues. In this paper, the Chair and a member of human resear ch ethics committees provide an insiders' point of view on how to demonstrate ethical conduct in health promotion research and quality improvement. Several common issues raised by health promotion research and evaluation are discussed including researcher integrity, conflicts of interest, use of information, consent and privacy. PMID- 26538344 TI - Testosterone enables growth and hypertrophy in fusion impaired myoblasts that display myotube atrophy: deciphering the role of androgen and IGF-I receptors. AB - We have previously highlighted the ability of testosterone (T) to improve differentiation and myotube hypertrophy in fusion impaired myoblasts that display reduced myotube hypertrophy via multiple population doublings (PD) versus their parental controls (CON); an observation which is abrogated via PI3K/Akt inhibition (Deane et al. 2013). However, whether the most predominant molecular mechanism responsible for T induced hypertrophy occurs directly via androgen receptor or indirectly via IGF-IR/PI3K/Akt pathway is currently debated. PD and CON C2C12 muscle cells were exposed to low serum conditions in the presence or absence of T (100 nM) +/- inhibitors of AR (flutamide/F, 40 MUm) and IGF-IR (picropodophyllin/PPP, 150 nM) for 72 h and 7 days (early/late muscle differentiation respectively). T increased AR and Akt abundance, myogenin gene expression, and myotube hypertrophy, but not ERK1/2 activity in both CON and PD cell types. Akt activity was not increased significantly in either cell type with T. Testosterone was also unable to promote early differentiation in the presence of IGF-IR inhibitor (PPP) yet still able to promote appropriate later increases in myotube hypertrophy and AR abundance despite IGF-IR inhibition. The addition of the AR inhibitor powerfully attenuated all T induced increases in differentiation and myotube hypertrophy with corresponding reductions in AR abundance, phosphorylated Akt, ERK1/2 and gene expression of IGF-IR, myoD and myogenin with increases in myostatin mRNA in both cell types. Interestingly, despite basally reduced differentiation and myotube hypertrophy, PD cells showed larger T induced increases in AR abundance vs. CON cells, a response abrogated in the presence of AR but not IGF-IR inhibitors. Furthermore, T induced increases in Akt abundance were sustained despite the presence of IGF-IR inhibition in PD cells only. Importantly, flutamide alone reduced IGF-IR mRNA in both cell types across time points, with an observed reduction in activity of ERK and Akt, suggesting that IGF-IR was transcriptionally regulated by AR. However, where testosterone increased AR protein content there was no increases observed in IGF IR gene expression. This suggested that sufficient AR was important to enable normal IGF-IR expression and downstream signalling, yet elevated levels of AR due to testosterone had no further effect on IGF-IR mRNA, despite testosterone increasing Akt abundance in the presence of IGF-IR inhibitor. In conclusion, testosterones ability to improve differentiation and myotube hypertrophy occurred predominately via increases in AR and Akt abundance in both CON and PD cells, with fusion impaired cells (PD) showing an increased responsiveness to T induced AR levels. Finally, T induced increases in myotube hypertrophy (but not early differentiation) occurred independently of upstream IGF-IR input, however it was apparent that normal AR function in basal conditions was required for adequate IGF-IR gene expression and downstream ERK/Akt activity. PMID- 26538346 TI - Treatment monitoring of 0.5% 5-fluorouracil and 10% salicylic acid in clinical and subclinical actinic keratoses with the combination of optical coherence tomography and reflectance confocal microscopy. AB - BACKGROUND: Reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) allow the observation in vivo of dynamic changes in response to non-surgical treatment of actinic keratosis and field of cancerisation. OBJECTIVE: To non-invasively assess the pharmacodynamic changes induced by treatment with low dose 5-fluorouracil and 10% salicylic acid by means of RCM and high-definition OCT in field cancerization and actinic keratosis. METHODS: Twenty patients aged >50 years with diagnosis of actinic keratosis on the head and face and indication for treatment with 0.5% 5-fluorouracil and 10% salicylic acid were enrolled. An area of 25 cm2 including visible type I and II AK and subclinical AK was treated once daily during 6 weeks and examination was performed with RCM and HD-OCT before treatment and 2 weeks after the end of treatment RESULTS: High-definition optical coherence tomography results at baseline of mean thickness of the stratum corneum and epidermis were in AK 10.4 (SD = 4.99) and 43.3 (SD = 24.01) MUm respectively and in subclinical AK 3.7 (SD = 2.15) and 30.05 (SD = 16.85) MUm. At week 8 (2 weeks after the end of treatment) measurements of stratum corneum and epidermis were significantly reduced in AK and subclinical AK for stratum corneum and epidermis. In RCM at week 8 scaling, detached corneocytes, atypical honeycomb, round nucleated cells in the spinosum granulosum layer, round vessels (dermal papillae), inflammatory cells and total AK score were significantly reduced in AK and subclinical AK. CONCLUSIONS: Evaluation of AK and subclinical AK by RCM and HD-OCT showed objective improvement after treatment with 5-fluorouracil and 10% salicylic acid. These methods allowed the study of dynamic changes in the tissue at a subclinical level. PMID- 26538347 TI - Association between brachial-ankle pulse wave velocity and progression of coronary artery calcium: a prospective cohort study. AB - BACKGROUND: Few studies have investigated the association between coronary artery calcium (CAC) progression and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). We examined the influence of the severity of baseline baPWV on CAC progression in a large prospective cohort. METHODS: A total of 1600 subjects who voluntarily participated in a comprehensive health-screening program between March 2010 and December 2013 and had baseline baPWV as well as CAC on baseline and serial follow-up computed tomography performed approximately 2.7 +/- 0.5 years apart were enrolled in the study. RESULTS: A total of 1124 subjects were included in the analysis (1067 men; mean age, 43.6 +/- 5.1 years). An increased CAC score was found in 318 subjects (28.3%) during the follow-up period. Baseline higher baPWV was significantly correlated with CAC progression, especially in subjects with third- and fourth-quartile values (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI] 1.33-3.15 and OR 2.14; 95% CI 1.34 3.41, respectively) compared with the lowest-quartile values (P for trend <0.001). A similar effect was observed in diabetic subjects. Among the 835 subjects with a baseline CAC score = 0, progression to CAC score >0 was associated with male sex, diabetes, and higher baPWV. However, among the 289 individuals with a baseline CAC score >0, only the presence of CAC itself was predictive of CAC progression. CONCLUSIONS: Higher arterial stiffness measured by baPWV could be significantly associated with CAC progression. PMID- 26538348 TI - Outcomes of Clostridium difficile infection in pediatric solid organ transplant recipients. AB - BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for CDI in part because of chemotherapy and prolonged hospitalization. METHODS: We utilized data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to study the incidence and outcomes related to CDI as a complicating factor in pediatric recipients of SOT. RESULTS: Our results demonstrate that hospitalized children with SOT have increased rates of infection, with the greatest risk for younger children with additional comorbidities and severe illness. The type of transplanted organ affects the risk for CDI, with the lowest incidence observed in renal transplant patients. CONCLUSION: The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, CDI is not an independent predictor of increased in- hospital mortality in these patients. PMID- 26538349 TI - Atypical psoriasis. PMID- 26538350 TI - Bioaggregate of photo-fermentative bacteria for enhancing continuous hydrogen production in a sequencing batch photobioreactor. AB - Hydrogen recovery through solar-driven biomass conversion by photo-fermentative bacteria (PFB) has been regarded as a promising way for sustainable energy production. However, a considerable fraction of organic substrate was consumed for the growth of PFB as biocatalysts, furthermore, these PFB were continuously washed out from the photobioreactor in continuous operation because of their poor flocculation. In this work, PFB bioaggregate induced by L-cysteine was applied in a sequencing batch photobioreactor to enhance continuous hydrogen production and reduce biomass washout. The effects of the hydraulic retention time (HRT), influent concentration and light intensity on hydrogen production of the photobioreactor were investigated. The maximum hydrogen yield (3.35 mol H2/mol acetate) and production rate (1044 ml/l/d) were obtained at the HRT of 96 h, influent concentration of 3.84 g COD/l, and light intensity of 200 W/m(2). With excellent settling ability, biomass accumulated in the photobioreactor and reached 2.15 g/l under the optimum conditions. Structural analysis of bioaggregate showed that bacterial cells were covered and tightly linked together by extracellular polymeric substances, and formed a stable structure. Therefore, PFB bioaggregate induced by L-cysteine is an efficient strategy to improve biomass retention capacity of the photobioreactor and enhance hydrogen recovery efficiency from organic wastes. PMID- 26538351 TI - Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer's Disease and Other Tauopathies. AB - Immunotherapy directed against tau is a promising treatment strategy for Alzheimer's Disease (AD) and tauopathies. We review initial studies on tau directed immunotherapy, and present data from our laboratory testing antibodies using the rTg4510 mouse model, which deposits tau in forebrain neurons. Numerous antibodies have been tested for their efficacy in treating both pathology and cognitive function, in different mouse models, by different routes of administration, and at different ages or durations. We report, here, that the conformation-specific antibody MC-1 produces some degree of improvement to both cognition and pathology in rTg4510. Pathological improvements as measured by Gallyas staining for fully formed tangles and phosphorylated tau appeared 4 days after intracranial injection into the hippocampus. We also examined markers for microglial activation, which did not appear impacted from treatment. Behavioral effects were noted after continuous infusion of antibodies into the lateral ventricle for approximately 2 weeks. We examined basic motor skills, which were not impacted by treatment, but did note cognitive improvements with both novel object and radial arm water maze testing. Our results support earlier reports in the initial review presented here, and collectively show promise for this strategy of treatment. The general absence of extracellular tau deposits may avoid the opsonization and phagocytosis mechanisms activated by antibodies against amyloid, and make anti tau approaches a safer method of immunotherapy for Alzheimer's disease. PMID- 26538352 TI - 'You Wouldn't have Your Granny Using Them': Drawing Boundaries Between Acceptable and Unacceptable Applications of Civil Drones. AB - Some industry and policy actors are concerned about public opposition to civil drones, in particular because of their association with military drones. However, very little is understood about public reactions to the technology. Strategies to 'manage public acceptance' have so far relied upon several untested assumptions. We conducted public engagement activities to explore citizens' visions of civil drones. Several insights counteracted the prevailing assumptions. Rejecting the notion of blanket support for or opposition to civil drones, we found that citizens make nuanced decisions about the acceptability of civil drones depending upon the purpose of the flight and the actors involved. The results are positioned in support for calls to strengthen the role of citizens in civil drone development and, in particular, to shift away from the current focus on citizens' acceptance of civil drone development towards the development of civil drones that are acceptable to citizens. PMID- 26538353 TI - Just a Cog in the Machine? The Individual Responsibility of Researchers in Nanotechnology is a Duty to Collectivize. AB - Responsible Research and Innovation (RRI) provides a framework for judging the ethical qualities of innovation processes, however guidance for researchers on how to implement such practices is limited. Exploring RRI in the context of nanotechnology, this paper examines how the dispersed and interdisciplinary nature of the nanotechnology field somewhat hampers the abilities of individual researchers to control the innovation process. The ad-hoc nature of the field of nanotechnology, with its fluid boundaries and elusive membership, has thus far failed to establish a strong collective agent, such as a professional organization, through which researchers could collectively steer technological development in light of social and environmental needs. In this case, individual researchers cannot innovate responsibly purely by themselves, but there is also no structural framework to ensure that responsible development of nanotechnologies takes place. We argue that, in such a case, individual researchers have a duty to collectivize. In short, researchers in situations where it is challenging for individual agents to achieve the goals of RRI are compelled to develop organizations to facilitate RRI. In this paper we establish and discuss the criteria under which individual researchers have this duty to collectivize. PMID- 26538354 TI - A comparison of the clinical outcomes of embryos derived from intracytoplasmic sperm injection after early fertilization check and conventional insemination using sibling oocytes. AB - PURPOSE: In order to identify the real contribution of early fertilization check (EFC) for reproductive outcome, we compared the developmental potential of embryos derived from intracytoplasmic sperm injection (ICSI) after EFS with those from conventional insemination in sibling oocytes. METHODS: Between April 2009 and April 2012, a total of 3249 oocytes in 386 patients were recruited following conventional insemination. Oocytes showing a second polar body (2ndPB) after an EFC were considered to be fertilized oocytes (IVF group), but, oocytes not showing a 2ndPB after EFC were placed into the ICSI group. The incidence of morphologically good embryos (MGE) on day 3, the blastocyst formation (BL), and the development of full blastocysts (full-BL) on day 5 were compared between the two groups. The clinical pregnancy rate was compared between the cycles with only conventional insemination or ICSI after EFC of the embryos being transferred. RESULTS: The fertilization rates in both the IVF and the ICSI groups were 48.1 and 73.9 %, respectively. The percentage of MGE in the ICSI group (40.8 %) was significantly lower than that in the IVF group (56.1 %, p < 0.01). The percentages of BL and full-BL in the ICSI group were significantly lower than those in the IVF group. The pregnancy rates were similar in both the groups. CONCLUSIONS: Checking fertilization earlier than the usual period contributed to an avoidance of lower fertilization. Moreover, the embryos derived from ICSI after EFC possessed a normal developmental potential. PMID- 26538355 TI - Breast cancer presentation and therapy in migrant versus native German patients: contrasting and convergent data of a retrospective monocentric study. AB - PURPOSE: The aim of this study was to identify differences between breast cancer patients with and without migrant background in Germany, especially differences concerning patient characteristics, tumor biology, diagnostics, therapy, and oncological outcome. PATIENTS AND METHODS: In 99 breast cancer patients (composed of 50 native, randomly selected Germans and 49 consecutively selected immigrants of Anatolian origin) who were operated due to breast cancer at the Heidelberg University Hospital between the years 2009-2012, relevant information was retrospectively reviewed. RESULTS: Patients with migrant background were significantly younger at the time of receiving the diagnosis of breast cancer than native German patients with an average age difference of nine years (p < 0.001). Moreover, immigrants needed a second operation for re-excision more frequently than native Germans (45 vs. 20 %, p = 0.01). The medication used for hormone therapy was significantly different between the two cohorts (p = 0.049). Although statistically not significant, a tendency towards difference was observed in six characteristics examined: Premenopausal status, estrogen receptor positive tumors, multifocal or bilateral tumors, BRCA-1 mutations, and an accompanying carcinoma in situ were more common in patients with migrant background. On the other hand, correspondence was found between both patient groups relating to tumor staging, grading and metastasis as well as surgical, drug, and radiologic therapies employed. Oncologic outcome data were not different either. CONCLUSION: A difference in age between breast cancer patients of diverse ethnic groups has already been described previously. The difference in the frequency of surgical re-excision might be explained by several factors like a young age at first diagnosis, premenopausal status, multifocal tumors and an accompanying carcinoma in situ which were more common in the migrant patients of this study and are known to increase the risk of re-excision. The medication used for hormonal therapy was also different between migrants and native Germans, which might be interpreted by the difference in patients' age and menopausal status. Of note, however, in the present study, the overall breast cancer outcome did not show any substantial disparity between the different ethnic patient groups investigated. PMID- 26538356 TI - Macrophage colony-stimulating factor (M-CSF) in first trimester maternal serum: correlation with pathologic pregnancy outcome. AB - PURPOSE: To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies. METHODS: This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free beta-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling. RESULTS: 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270 +/- 91 pg/ml (p = 0.032), whereas cases of trisomy 13 (183 +/- 68 pg/ml) and trisomy 18 (143 +/- 40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free beta-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M CSF. CONCLUSIONS: M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research. PMID- 26538357 TI - Replacement of oxytocin bolus administration by infusion: influences on postpartum outcome. AB - PURPOSE: Postpartum haemorrhage (PPH) represents a leading cause of maternal morbidity and mortality. Giving oxytocin after birth reduces the risk for PPH. It has never been tested whether different methods of oxytocin administration affect the maternal outcome. This study aims to compare the infusion versus the bolus application of oxytocin after singleton vaginal delivery. METHODS: This retrospective monocentre study compares the incidence of clinically relevant postpartum complications in women receiving 5 IE of oxytocin as a bolus or as a 100 ml-infusion over 5 min, given immediately after birth. Included were women delivering singletons vaginally at term. We used propensity score weighting to compare outcomes between women receiving bolus and infusion and to minimize the selection bias in this retrospective cohort. RESULTS: 1765 patients were included. Patient characteristics were balanced. We found no significant differences for the combined overall postpartum adverse outcome (the incidence of PPH, manual removal of the placenta and/or curettage). For the single outcomes, we observed a significantly higher frequency of manual removal of the placenta (Odds ratio 1.47, 95 % CI 1.02-2.13) and a slightly higher but clinically not relevant estimated blood loss (Relative effect 1.05, 95 % CI 1.01-1.10) in the infusion group. CONCLUSION: The data show a tendency towards more complications in the infusion group. It is related to a more frequent need for manual removal of the placenta. PMID- 26538358 TI - Slow chlorine releasing compounds: A viable sterilisation method for bioabsorbable nanocomposite biomaterials. AB - OBJECTIVE: Selection of the appropriate sterilisation method for biodegradable materials has been a challenging task. Many conventional sterilisation methods are not suitable for the next generation of biomaterials, mainly due to their complex composition, based on nanomaterials, often incorporating bioactive moieties. In this study, we investigate sterilisation efficacy of slow chlorine releasing compound sodium dichloroisocyanurate dihydrate (SDIC) for polyhedral oligomeric silsesquioxane (POSS)-poly(caprolactone urea-urethane) (PCL) scaffolds in comparison with conventional sterilisation methods. METHODS: POSS-PCL scaffolds were subjected to 70% ethanol, UV, and SDIC sterilisation methods. Samples were immersed in tryptone soya broth (TSB) and thioglycollate medium (THY) and after seven days visually inspected for signs of microbial growth. Bulk and surface properties and molecular weight distribution profiles of the scaffolds after sterilization were investigated using FTIR analysis, surface hydrophilicity, scanning electron microscopy analysis, tensile strength testing, and gel-permeation chromatography (GPC). Adipose-derived stem cells (ADSC) were seeded on the scaffolds and AlamarBlue(r) viability assay was performed to investigate cell metabolic activity. Confocal imaging of rhodamine phalloidin and Dapi stained ADSC on scaffolds was used to demonstrate cell morphology. RESULTS: GPC results showed that autoclaving led to a significant decrease in the molecular weight of POSS-PCL, whereas ethanol caused visible deformation of the polymer 3D structure and UV radiation did not effectively sterilise the scaffolds. AlamarBlue(r) analysis showed metabolic activity close to that of tissue culture plastic for ethanol and SDIC. CONCLUSION: SDIC sterilisation can be safely applied to biodegradable scaffolds unsuitable for the more common sterilisation methods. PMID- 26538359 TI - Evaluation of Heart Function in Patients With Hemophilia. AB - There are conflicting reports about the protective effect of hemophilia on the occurrence of ischemic heart disease. This study focuses on evaluation of heart function in patients with hemophilia. Cross-sectional, case-control study was done on all patients with hemophilia A or B who came to hemophilia center, and data were compared to controls. The data were collected from their charts, and heart function was evaluated by 2-dimensional, Doppler and pulse tissue Doppler. The serum troponin I level was measured in all patients as a marker of myocardial damage. Fifty patients with hemophilia took part in this study. All of them were male with mean age 29.1 years. Systolic blood pressure (mean = 121.52 +/- 11 vs 115.61 +/- 9.81, P = .038) and diastolic (mean = 81.94 +/- 4.51 vs 75.21 +/- 3.95, P = .042) blood pressure were higher in the patients. Five (10%) patients had systolic hypertension and 7 (14%) patients had diastolic hypertension. The M mode echocardiography results showed that interventricular septum in diastole in patients with hemophilia (mean 1.143 +/- 0.29) was significantly thicker than the control group (mean 0.828 +/- 0.22, P < .001). Tissue Doppler echocardiography showed that late diastolic velocity of septum (Aa; P = .030), systolic velocity (S) of lateral mitral valve ( P = .006), late diastolic velocity of lateral mitral (Aa) annulus ( P = .038), and late velocity of (Aa) tricuspid ( P = .004) had significant difference compared with the control group ( P < .05). Troponin enzyme level was < 0.1 in all patients. Patients with hemophilia had higher blood pressure and more hypertension. Echocardiographic study of patients with hemophilia showed some increase in septal thickness and changes in diastolic dysfunction. PMID- 26538360 TI - Benefits of radial head excision in patients with haemophilia: mid-term functional results. AB - INTRODUCTION: Recurrent haemarthrosis in haemophilic patients result with arthropathy of the radiocapitellar joint and blockage of the forearm rotation. AIM: The aim of this study is to evaluate the mid-term results of radial head excision with partial synovectomy in severe haemophilic patients retrospectively. METHODS: Persistent pain and decreased forearm rotation were the main indications for radial head excision. Between 2002 and 2013, radial head excisions were performed for 14 elbows of 14 patients. Eleven patients were haemophilia A, whereas two patients were haemophilia B patients and the remaining one had von Willebrand (Type 3) disease. The mean age of the patients was 29 at the time of the surgery. The mean follow-up was 51 (12-155) months. VAS (visual analogue score) for pain, forearm rotation, qDASH and MEPS (Mayo Elbow Performance Score) were used as the primary outcome parameters. RESULTS: The mean VAS decreased significantly from 6.5 preoperatively to 2.2 at the final follow-up (P = 0.0003). The mean forearm rotation increased from 40 degrees to 115 degrees respectively (P = 0.0007). In two patients, efficacious rotation increase was not achieved due to distal radioulnar joint problems. The mean qDASH score and MEPS were 18.1 and 87.5 at the latest follow-up, respectively, where four patients had excellent and 10 patients had good results. CONCLUSIONS: Radial head excision is a safe and effective procedure for haemophiliac patients with radiocapitellar arthropathy and decreased forearm rotation. Distal radioulnar joint should be evaluated preoperatively which may impair the results. PMID- 26538361 TI - The alpha-hydroxyketone LAI-1 regulates motility, Lqs-dependent phosphorylation signalling and gene expression of Legionella pneumophila. AB - The causative agent of Legionnaires' disease, Legionella pneumophila, employs the autoinducer compound LAI-1 (3-hydroxypentadecane-4-one) for cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, comprising the autoinducer synthase LqsA, the sensor kinases LqsS and LqsT, as well as the response regulator LqsR. Lqs-regulated processes include pathogen-host interactions, production of extracellular filaments and natural competence for DNA uptake. Here we show that synthetic LAI-1 promotes the motility of L. pneumophila by signalling through LqsS/LqsT and LqsR. Upon addition of LAI-1, autophosphorylation of LqsS/LqsT by [gamma-(32) P]-ATP was inhibited in a dose-dependent manner. In contrast, the Vibrio cholerae autoinducer CAI-1 (3-hydroxytridecane-4-one) promoted the phosphorylation of LqsS (but not LqsT). LAI-1 did neither affect the stability of phospho-LqsS or phospho LqsT, nor the dephosphorylation by LqsR. Transcriptome analysis of L. pneumophila treated with LAI-1 revealed that the compound positively regulates a number of genes, including the non-coding RNAs rsmY and rsmZ, and negatively regulates the RNA-binding global regulator crsA. Accordingly, LAI-1 controls the switch from the replicative to the transmissive growth phase of L. pneumophila. In summary, the findings indicate that LAI-1 regulates motility and the biphasic life style of L. pneumophila through LqsS- and LqsT-dependent phosphorylation signalling. PMID- 26538362 TI - Light up Live Cell Nuclear Envelope in Real-Time Using a Two-Photon Absorption and AIE Chromophore. AB - In this letter, aggregation from two-photon absorption (2PA) molecules in living cells were firstly observed and the related aggregation induced emission (AIE) properties were investigated as a cell tracer for L ((Z)-3-(4-(Bis(4 ethoxyphenyl) amino)phenyl)-2-(4-amino-phenyl)- acrylonitrile cyano-substituted ) based on triphenylamine with D-pi-A model. L was further used as a two-photon absorption (2PA, lambdaex = 900, lambdaem = 550 nm delta = 156 GM) live-cell marker for real-time, long-term cell growth and proliferation monitoring, with rapidly adhering whole intracellular membrane-rich system. Remarkably, different from existing organic AIE chromophores and other commercially available probes, L exhibited intense intracellular-AIE property with stable nuclear envelope (NE) staining under two-photon excited microscopy (TPEM) through detailed in cellulo studies. PMID- 26538363 TI - Synthesis, Characterization and Fluorescence Properties of Zn(II) and Cu(II) Complexes: DNA Binding Study of Zn(II) Complex. AB - Zinc(II) and copper(II) complexes containing Schiff base, 2- methoxy-6((E) (phenylimino) methyl) phenol ligand (HL) were synthesized and characterized by elemental analysis, IR, NMR, and single crystal X-ray diffraction technique. The fluorescence properties and quantum yield of zinc complex were studied. Our data showed that Zn complex could bind to DNA grooves with Kb = 10(4) M(-1). Moreover, Zn complex could successfully be used in staining of DNA following agarose gel electrophoresis. MTT assay showed that Zn complex was not cytotoxic in MCF-7 cell line. Here, we introduce a newly synthesized fluorescence probe that can be used for single and double stranded DNA detection in both solution and agarose gels. PMID- 26538364 TI - Interleukin-6 as a potential positive modulator of human beta-cell function: an exploratory analysis-the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 6. AB - AIMS: Recent studies in mouse models of T2D showed that interleukin-6 (IL-6), released from skeletal muscle, is associated with increased glucose-dependent insulin secretion. Few data currently exist exploring the relationship between IL 6 and beta-cell function in humans. We investigated whether IL-6 is positively associated with beta-cell function in newly diagnosed T2D. We extended the same analyses to IL-10, because it regulated similarly to IL-6 in skeletal muscle, and TNF-alpha and C-reactive protein (CRP), as general biomarkers of inflammation. METHODS: In 330 VNDS participants, we assessed (1) basal plasma concentrations of IL-6, IL-10, TNF-alpha, and CRP; (2) beta-cell function, estimated by OGTT minimal modeling and expressed as derivative (DC) and proportional control (PC); (3) insulin sensitivity, by euglycemic insulin clamp. RESULTS: IL-6 was positively associated with PC in both univariate analysis (p = 0.04) and after adjustment for age, sex, BMI, HbA1c, and M-clamp (p = 0.01). HbA1c was the major independent contributor to the overall variance of PC (16 %), followed by BMI and IL-6 (~2 % each). Similar results were obtained for IL-10 (p = 0.048, univariate; p = 0.04, fully adjusted). TNF-alpha and CRP were not significantly associated with any component of beta-cell function. CONCLUSIONS: Our data are the first evidence in human subjects that an endocrine loop involving IL-6 may act as positive modulator of glucose-dependent insulin secretion. Further functional studies are needed to corroborate IL-6 system as a potential druggable target in diabetes. CLINICAL TRIAL REGISTRATION NUMBER: NCT01526720 ( http://www.clinicaltrial.gov ). PMID- 26538365 TI - Mesoporous gold sponges: electric charge-assisted seed mediated synthesis and application as surface-enhanced Raman scattering substrates. AB - Mesoporous gold sponges were prepared using 4-dimethylaminopyridine (DMAP) stabilized Au seeds. This is a general process, which involves a simple template free method, room temperature reduction of HAuCl4.4H2O with hydroxylamine. The formation process of mesoporous gold sponges could be accounted for the electrostatic interaction (the small Au nanoparticles (~3 nm) and the positively charged DMAP-stabilized Au seeds) and Ostwald ripening process. The mesoporous gold sponges had appeared to undergo electrostatic adsorption initially, sequentially linear aggregation, welding and Ostwald ripening, then, they randomly cross link into self-supporting, three-dimensional networks with time. The mesoporous gold sponges exhibit higher surface area than the literature. In addition, application of the spongelike networks as an active material for surface-enhanced Raman scattering has been investigated by employing 4 aminothiophenol (4-ATP) molecules as a probe. PMID- 26538366 TI - Platinized Graphene/ceramics Nano-sandwiched Architectures and Electrodes with Outstanding Performance for PEM Fuel Cells. AB - For the first time a novel oxygen reduction catalyst with a 3D platinized graphene/nano-ceramic sandwiched architecture is successfully prepared by an unusual method. Herein the specific gravity of graphene nanosheets (GNS) is tailored by platinizing graphene in advance to shorten the difference in the specific gravity between carbon and SiC materials, and then nano-SiC is well intercalated into GNS interlayers. This nano-architecture with highly dispersed Pt nanoparticles exhibits a very high oxygen reduction reaction (ORR) activity and polymer electrolyte membrane (PEM) fuel cell performance. The mass activity of half cells is 1.6 times of that of the GNS supported Pt, and 2.4 times that of the commercial Pt/C catalyst, respectively. Moreover, after an accelerated stress test our catalyst shows a predominantly electrochemical stability compared with benchmarks. Further fuel cell tests show a maximum power density as high as 747 mW/cm(2) at low Pt loading, which is more than 2 times higher than that of fuel cells with the pristine graphene electrode. PMID- 26538367 TI - An autochthonous case of cystic echinococcosis in Finland, 2015. AB - We report a case of pulmonary cystic echinococcosis in a child from eastern Finland with no history of travelling abroad. The cyst was surgically removed and the organism molecularly identified as Echinococcus canadensis genotype G10. This parasite is maintained in eastern Finland in a sylvatic life cycle involving wolves and moose; in the present case, the infection was presumably transmitted by hunting dogs. PMID- 26538369 TI - Comment: Analysis of the influence of dabigatran on coagulation factors and inhibitors. PMID- 26538368 TI - Features of COPD patients by comparing CAT with mMRC: a retrospective, cross sectional study. AB - BACKGROUND: The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used. AIMS: This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC. METHODS: This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed. RESULTS: Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ?10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT?10/mMRC 0-1 subgroup had more wheezing than CAT<10/mMRC?2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment. CONCLUSIONS: The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD. PMID- 26538370 TI - Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition. AB - Myocardial infarction (MI), which is characterized by chamber dilation and LV dysfunction, is associated with substantially higher mortality. We investigated the effects and underlying mechanisms of Luteolin on post-infarction cardiac dysfunction. Myocardial infarction was constructed by left anterior descending coronary artery ligation. In vitro, cultured neonatal cardiomyocytes subjected to simulated MI were used to probe mechanism. Luteolin significantly improved cardiac function, decreased cardiac enzyme and inflammatory cytokines release after MI. Enhanced autophagic flux as indicated by more autophagosomes puncta, less accumulation of aggresomes and P62 in the neonatal cardiomyocytes after hypoxia was observed in the Luteolin pre-treatment group. Western blot analysis also demonstrated that Luteolin up-regulated autophagy in the cardiomyocytes subjected to simulated MI injury. Furthermore, Luteolin increased mitochondrial membrane potential, adenosine triphosphate content, citrate synthase activity and complexes I/II/III/IV/V activities in the cardiomyocytes subjected to simulated MI injury. Interestingly, mammalian sterile 20-like kinase 1 (Mst1) knockout abolished the protective effects of Luteolin administration. Luteolin enhances cardiac function, reduces cardiac enzyme and inflammatory markers release after MI. The protective effects of Luteolin are associated with up-regulation of autophagy and improvement of mitochondrial biogenesis through Mst1 inhibition. PMID- 26538371 TI - Anterolateral thigh flap for axillary reconstruction after sarcoma resection. AB - BACKGROUND: Reconstruction of extensive axillary defects after sarcoma resection presents a challenging problem in reconstructive microsurgery. The purpose of this report was to investigate the feasibility of the free anterolateral thigh (ALT) flap for oncologic axillary reconstruction. METHODS: The extensive axillary defects in six patients with sarcoma was reconstructed using a free ALT flap. The defect size ranged from 15 * 11 to 28 * 25 cm2 . Five patients had recurrent cases and the ipsilateral latissimus dorsi flap had been already used in three patients. Two patients with a full-thickness defect underwent chest wall reconstruction with the iliotibial tract. RESULTS: All flaps survived completely and the wounds healed without complications in all patients. CONCLUSIONS: The free ALT flap is an ideal flap for axillary reconstruction after extensive sarcoma resection. It can be tailored to the requirements of the individual's defect and provides durable coverage for the axillary neurovascular bundle and intrathoracic structures. Flap harvesting in the lateral decubitus position enables a two-team approach. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:378 383, 2016. PMID- 26538372 TI - Pulmonary Vein Isolation With Incomplete Antral Ablation Lines: Is More Ablation Necessary? Results of a Randomized Trial. AB - BACKGROUND: A full circumferential set of antral lesions is not always required for bidirectional pulmonary vein conduction block. It is unknown whether a partial lesion set that isolates the veins will have clinical success rates similar to a full circumferential lesion set, and if procedural times or procedural risk will be affected. METHODS: We performed a prospective, randomized clinical trial to test the hypothesis that a partial lesion set that isolates the pulmonary veins has comparable clinical success rate and shorter procedure times compared to a strategy of completing the circumferential lesion set once the veins are isolated. RESULTS: A total of 119 patients were enrolled, 59 randomized to circumferential ablation, and 60 to segmental. Mean age was 58.3 +/- 10.1, 77% male. Mean procedure time was 221.0 +/- 46.9 minutes in circumferential and 224.7 +/- 51.3 in segmental (P = 0.68). Twelve-month freedom from AF recurrence was 61.3% overall, 64.4% in circumferential, and 58.3% in segmental (P = 0.50). Among 25 segmental patients with AF recurrence, 23 underwent second ablation. Among 33 areas of conduction recovery, 23 (70%) occurred in segments ablated at first procedure and 10 (30%) in segments not previously ablated, suggesting reversible conduction block from edema. CONCLUSION: No difference in AF recurrence or procedure time is detectable in a sample of 119 patients randomized to segmental or circumferential antral ablation to achieve pulmonary vein isolation. Second ablation procedures confirmed that some antral sites do not require ablation. A segmental approach results in unacceptably high rates of untargeted or recovered antral sites to make this approach feasible. PMID- 26538373 TI - Impact of Chronic Kidney Disease on Long-Term Outcome of Coronary Artery Bypass Grafting in Patients With Diabetes Mellitus. AB - BACKGROUND: The aim of this study was to compare the short- and long-term outcomes of CABG in diabetes mellitus (DM) patients according to eGFR. METHODS AND RESULTS: A total of 573 DM patients receiving CABG between 1997 and 2012 were stratified according to preoperative eGFR: normal or mild chronic kidney disease (CKD), eGFR >=60 ml/min/1.73 m(2); moderate CKD, eGFR 30-60 ml/min/1.73 m(2); severe CKD, eGFR <30 ml/min/1.73 m(2); and severe CKD requiring hemodialysis (HD). Off-pump and bilateral internal thoracic artery (BITA) grafting rates were 83.4 and 62.3%, respectively. Mediastinitis and in-hospital mortality rates were both 1.4%. On logistic regression analysis, preoperative congestive heart failure and CKD severity were independent predictors of postoperative renal failure and major complications. The mean follow-up period was 5.7 years (range, 0-15.5 years). Estimated 5-year survival (92.9+/-1.6%, 82.8+/-3.3%, and 47.3+/-7.0%, respectively, P<0.001) significantly decreased with declining kidney function. On Cox hazard modeling, CKD severity was an independent predictor of major cerebrocardiovascular events (normal/mild: hazard ratio [HR], 1; moderate: HR, 1.35; severe: HR, 1.83; HD: HR, 2.0, P=0.016) and of overall survival (normal/mild: HR, 1; moderate: HR, 1.65; severe: HR, 5.96; HD: HR, 10.93, P<0.001). BITA grafting was a strong protective factor for overall survival (HR, 0.63; P=0.022). CONCLUSIONS: In DM patients, early- and long-term outcomes after CABG are strongly influenced by CKD progression. PMID- 26538374 TI - Preoperative Tissue Doppler Imaging-Derived Atrial Conduction Time Predicts Postoperative Atrial Fibrillation in Patients Undergoing Mitral Valve Surgery for Mitral Valve Regurgitation. AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and may result in stroke, heart failure and poor prognosis. This study evaluated a novel index of total atrial conduction time derived from the P wave onset (lead II) to the peak A' wave on tissue Doppler imaging (PA-TDI duration) in patients undergoing mitral valve surgery (MVS) for mitral valve regurgitation. METHODS AND RESULTS: Seventy-three patients undergoing MVS had transthoracic echocardiography with tissue Doppler imaging preoperatively and were monitored postoperatively with continuous electrocardiographic telemetry for 14 days. Preoperative characteristics, echocardiographic data, operative data and postoperative findings were compared between patients with (n=44) and without (n=29) POAF. Postoperative cardiac events were higher in patients with than without POAF (12/44, 27% vs. 3/29, 10%; P=0.0798) and cerebral events occurred in only 2 POAF patients. On multivariate analysis the independent predictors of POAF were degenerative disease etiology (OR, 4.61; 95% CI: 1.41-15.0; P=0.0112) and PA TDI duration (OR, 1.04; 95% CI: 1.01-1.07; P=0.0048). On ROC curve analysis a PA TDI cut-off of 159.4 ms was optimal for predicting POAF. CONCLUSIONS: PA-TDI duration was an independent predictor of POAF after MVS. Patients with PA-TDI duration >159.4 ms should be considered high risk and treated appropriately to improve outcome. PMID- 26538375 TI - Ultra-flexible Piezoelectric Devices Integrated with Heart to Harvest the Biomechanical Energy. AB - Power supply for medical implantable devices (i.e. pacemaker) always challenges not only the surgery but also the battery technology. Here, we report a strategy for energy harvesting from the heart motion by using ultra-flexible piezoelectric device based on lead zirconate titanate (PZT) ceramics that has most excellent piezoelectricity in commercial materials, without any burden or damage to hearts. Experimental swine are selected for in vivo test with different settings, i.e. opened chest, close chest and awake from anesthesia, to simulate the scenario of application in body due to their hearts similar to human. The results show the peak-to-peak voltage can reach as high as 3 V when the ultra-flexible piezoelectric device is fixed from left ventricular apex to right ventricle. This demonstrates the possibility and feasibility of fully using the biomechanical energy from heart motion in human body for sustainably driving implantable devices. PMID- 26538376 TI - Brain modularity across the theropod-bird transition: testing the influence of flight on neuroanatomical variation. AB - Living birds constitute the only vertebrate group whose brain volume relative to body size approaches the uniquely expanded values expressed by mammals. The broad suite of complex behaviors exhibited by crown-group birds, including sociality, vocal learning, parental care, and flying, suggests the origins of their encephalization was likely driven by a mosaic of selective pressures. If true, the historical pattern of brain expansion may be more complex than either a gradual expansion, as proposed by early studies of the avian brain, or a sudden expansion correlating with the appearance of flight. The origins of modern avian neuroanatomy are obscured by the more than 100 million years of evolution along their phylogenetic stem (from the origin of the modern radiation in the Middle Jurassic to the split from crocodile-line archosaurs). Here we use phylogenetic comparative approaches to explore which evolutionary scenarios best explain variation in measured volumes of digitally partitioned endocasts of modern birds and their non-avian ancestors. Our analyses suggest that variation in the relative volumes of the endocranium and cerebrum explain most of the structural variation in this lineage. Generalized multi-regime Ornstein-Uhlenbeck (OU) models suggest that powered flight does not appear to be a driver of observed variation, reinforcing the hypothesis that the deep history of the avian brain is complex, with nuances still to be discovered. PMID- 26538377 TI - Lung cancer screening: a systematic review of clinical practice guidelines. AB - BACKGROUND: Lung cancer screening using low-dose computed tomography presents an exciting development for high-risk individuals. Several expert bodies and governments have recently issued and updated their clinical practice guidelines (CPGs) for lung cancer screening. We evaluate the CPGs and compare and contrast the recommendations between them. METHODS: We searched seven databases (MEDLINE, EMBASE, TRIP, NGC, SIGN, GIN, CMA Infobase) to find CPGs, and used the appraisal of guidelines for research and evaluation instrument (AGREE-II) to evaluate them. We also assessed the recommendations within each CPG. RESULTS: Of the eight CPGs included, four guidelines were regarded as high in quality (60%) based on rigour of development and effectively targeting 4-5 of the six domains according to the AGREE-II criteria. Most CPGs' recommendations for the lung cancer screening of high-risk individuals, the associated screening parameters and the benefit vs. harm of screening were consistent. However, there is still variation among the CPGs reviewed in this study. CONCLUSIONS: The qualities of the selected CPGs vary and there is potential to improve the qualities among and between each. Specifically, more evidence is needed to support the recommendations such as a larger cohort of high-risk participants, and further analysis of the lung cancer screening interval, the benefit vs. harm of lung cancer screening, the timing and rigour of follow-up and availability of effective treatments. PMID- 26538378 TI - Evaluation of low fluoride toothpaste using primary enamel and a validated pH cycling model. AB - AIM: To develop and validate pH-cycling model for primary enamel, which was then used to evaluate the anti-caries potential of fluoride toothpastes. DESIGN: Human primary enamel slabs were subjected to pH-cycling model for 10 days and maintained for 6 h in demineralizing solution and 18 h in remineralizing solution daily. Twice/day, the slabs were treated. To validate it, the treatments were water or solutions containing 62.5, 125, 250, and 375 MUg F/mL. Commercial toothpastes containing no fluoride, 500, 1100, and 1450 MUg F/g were evaluated. Demineralization was assessed by percentage of surface hardness loss (%SHL) and cross-sectional hardness (DeltaS). Fluoride dose-response effect was analysed by quadratic regression and the effects of toothpastes by Tukey's test. RESULTS: Dose-response effect was found between fluoride concentration and %SHL (R2 = 0.7047; P < 0.01) or DeltaS (R2 = 0.4465; P < 0.01). %SHL and DeltaS (mean +/- SD) for the group treated with 500 MUg F/g toothpaste was 36.6 +/- 8.0 and 6298.5 +/- 1221.3, respectively, which were significantly higher than those treated with 1100 (25.2 +/- 8.7; 4565.7 +/- 1122) and 1450 MUg F/g (24.2 +/- 5.2; 2339.1 +/- 879.7) toothpastes. CONCLUSION: The developed pH-cycling model may be used to evaluate and compare the anti-caries potential of toothpaste formulations with low fluoride concentration because it presents dose-response effects on the reduction of primary enamel demineralization. PMID- 26538379 TI - The influence of mothers' and fathers' sensitivity in the first year of life on children's cognitive outcomes at 18 and 36 months. AB - BACKGROUND: There has been increasing interest in the relative effects of mothers' and fathers' interactions with their infants on later development. However to date there has been little work on children's cognitive outcomes. METHODS: We examined the relative influence of fathers' and mothers' sensitivity during interactions with their children at the end of the child's first year (10 12 months, n = 97), on child general cognitive development at 18 months and language at 36 months. RESULTS: Both parents' sensitivity was associated with cognitive and language outcomes in univariate analyses. Mothers' sensitivity, however, appeared to be associated with family socio-demographic factors to a greater extent that fathers' sensitivity. Using path modelling the effect of paternal sensitivity on general cognitive development at 18 months and language at 36 months was significantly greater than the effect of maternal sensitivity, when controlling for socio-demographic background. In relation to language at 36 months, there was some evidence that sensitivity of one parent buffered the effect of lower sensitivity of the other parent. CONCLUSIONS: These findings suggest that parental sensitivity can play an important role in children's cognitive and language development, and that higher sensitivity of one parent can compensate for the lower sensitivity of the other parent. Replication of these findings, however, is required in larger samples. PMID- 26538380 TI - More on the use of bisphosphonates in the prevention and treatment of osteoporosis. PMID- 26538382 TI - Comment on 'Investigating the effect of the Transcendental Meditation Technique on blood pressure: a systematic review and meta-analysis'. PMID- 26538381 TI - A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery. AB - Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID- 26538383 TI - Elearning approaches to prevent weight gain in young adults: A randomized controlled study. AB - OBJECTIVE: Preventing obesity among young adults should be a preferred public health approach given the limited efficacy of treatment interventions. This study examined whether weight gain can be prevented by online approaches using two different behavioral models, one overtly directed at obesity and the other covertly. METHODS: A three-group parallel randomized controlled intervention was conducted in 2012-2013; 20,975 young adults were allocated a priori to one control and two "treatment" groups. Two treatment groups were offered online courses over 19 weeks on (1) personal weight control ("Not the Ice Cream Van," NTICV) and, (2) political, environmental, and social issues around food ("Goddess Demetra," "GD"). Control group received no contact. The primary outcome was weight change over 40 weeks. RESULTS: Within-group 40-week weight changes were different between groups (P < 0.001): Control (n = 2,134): +2.0 kg (95% CI = 1.5, 2.3 kg); NTICV (n = 1,810): -1.0 kg (95% CI = -1.3, -0.5); and GD (n = 2,057): 1.35 kg (95% CI = -1.4 to -0.7). Relative risks for weight gain vs. CONTROL: NTICV = 0.13 kg (95% CI = 0.10, 0.15), P < 0.0001; GD = 0.07 kg (95% CI = 0.05, 0.10), P < 0.0001. CONCLUSIONS: Both interventions were associated with prevention of the weight gain observed among control subjects. This low-cost intervention could be widely transferable as one tool against the obesity epidemic. Outside the randomized controlled trial setting, it could be enhanced using supporting advertising and social media. PMID- 26538384 TI - Aligned deposition and electrical measurements on single DNA molecules. AB - A reliable method of deposition of aligned individual dsDNA molecules on mica, silicon, and micro/nanofabricated circuits is presented. Complexes of biotinylated double stranded poly(dG)-poly(dC) DNA with avidin were prepared and deposited on mica and silicon surfaces in the absence of Mg(2+) ions. Due to its positive charge, the avidin attached to one end of the DNA anchors the complex to negatively charged substrates. Subsequent drying with a directional gas flow yields DNA molecules perfectly aligned on the surface. In the avidin-DNA complex only the avidin moiety is strongly and irreversibly bound to the surface, while the DNA counterpart interacts with the substrates much more weakly and can be lifted from the surface and realigned in any direction. Using this technique, avidin-DNA complexes were deposited across platinum electrodes on a silicon substrate. Electrical measurements on the deposited DNA molecules revealed linear IV-characteristics and exponential dependence on relative humidity. PMID- 26538385 TI - Lifeact and Utr230 induce distinct actin assemblies in cell nuclei. AB - Nuclear actin assembly in somatic cells has been an enigma for a long time. Recently, with the advancement of novel F-actin probes, researchers have started to uncover this mystery. In this study, we investigated the actin dynamics in somatic cell nuclei using two probes: Lifeact and Utr230. Surprisingly, we observed that both Lifeact and Utr230 significantly interfered with actin dynamics in cell nuclei. Moreover, these two probes induced distinct patterns of nuclear actin assembly. While Lifeact induced filamentous actin assembly in cell nuclei, Utr230 led to various patterns of actin aggregates, including fibers, small puncta, and large patches. Moreover, the interference of actin dynamics by Lifeact was limited to nuclear actin, while Utr230 induced actin aggregation in both the nucleus and cytoplasm. Using time-lapse microscopy, we found that Lifeact-induced actin fibers remained steady over hours of observation, indicating a deficiency of nuclear F-actin reorganization. These results suggest that Lifeact and Utr230 both interfere with nuclear actin dynamics but with distinct mechanisms. This is an important finding for research on nuclear actin assembly and highlights the potential value of these two probes for exploring the native mechanisms underlying nuclear actin dynamics, which appear to be altered in the presence of these probes. PMID- 26538386 TI - Online Resources for Engaging Students in Bioethical Discussions. PMID- 26538387 TI - Measuring Networking as an Outcome Variable in Undergraduate Research Experiences. AB - The aim of this paper is to propose, present, and validate a simple survey instrument to measure student conversational networking. The tool consists of five items that cover personal and professional social networks, and its basic principle is the self-reporting of degrees of conversation, with a range of specific discussion partners. The networking instrument was validated in three studies. The basic psychometric characteristics of the scales were established by conducting a factor analysis and evaluating internal consistency using Cronbach's alpha. The second study used a known-groups comparison and involved comparing outcomes for networking scales between two different undergraduate laboratory courses (one involving a specific effort to enhance networking). The final study looked at potential relationships between specific networking items and the established psychosocial variable of project ownership through a series of binary logistic regressions. Overall, the data from the three studies indicate that the networking scales have high internal consistency (alpha = 0.88), consist of a unitary dimension, can significantly differentiate between research experiences with low and high networking designs, and are related to project ownership scales. The ramifications of the networking instrument for student retention, the enhancement of public scientific literacy, and the differentiation of laboratory courses are discussed. PMID- 26538388 TI - Concept Maps for Improved Science Reasoning and Writing: Complexity Isn't Everything. AB - A pervasive notion in the literature is that complex concept maps reflect greater knowledge and/or more expert-like thinking than less complex concept maps. We show that concept maps used to structure scientific writing and clarify scientific reasoning do not adhere to this notion. In an undergraduate course for thesis writers, students use concept maps instead of traditional outlines to define the boundaries and scope of their research and to construct an argument for the significance of their research. Students generate maps at the beginning of the semester, revise after peer review, and revise once more at the end of the semester. Although some students revised their maps to make them more complex, a significant proportion of students simplified their maps. We found no correlation between increased complexity and improved scientific reasoning and writing skills, suggesting that sometimes students simplify their understanding as they develop more expert-like thinking. These results suggest that concept maps, when used as an intervention, can meet the varying needs of a diverse population of student writers. PMID- 26538389 TI - A Pharmacology-Based Enrichment Program for Undergraduates Promotes Interest in Science. AB - There is a strong need to increase the number of undergraduate students who pursue careers in science to provide the "fuel" that will power a science and technology-driven U.S. economy. Prior research suggests that both evidence-based teaching methods and early undergraduate research experiences may help to increase retention rates in the sciences. In this study, we examined the effect of a program that included 1) a Summer enrichment 2-wk minicourse and 2) an authentic Fall research course, both of which were designed specifically to support students' science motivation. Undergraduates who participated in the pharmacology-based enrichment program significantly improved their knowledge of basic biology and chemistry concepts; reported high levels of science motivation; and were likely to major in a biological, chemical, or biomedical field. Additionally, program participants who decided to major in biology or chemistry were significantly more likely to choose a pharmacology concentration than those majoring in biology or chemistry who did not participate in the enrichment program. Thus, by supporting students' science motivation, we can increase the number of students who are interested in science and science careers. PMID- 26538390 TI - Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells. AB - The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph gene encoding PH was deleted in an invasive Hif isolate. The dissociation constant (KD) of the interaction between recombinant PH and Vn was 2.2 MUM, as revealed by Biolayer interferometry. We found that PH has different regions for simultaneous interaction with both Vn and factor H, and that it recognized the C-terminal part of Vn (aa 352-362). Importantly, PH-dependent Vn binding resulted in better survival of the wild-type Hif or PH-expressing Escherichia coli when exposed to human serum. Finally, we observed that PH mediated an increased bacterial adherence to alveolar epithelial cells in the presence of Vn. In conclusion, our study reveals that PH most likely plays an important role in Hif pathogenesis by increasing serum resistance and adhesion to the airways. PMID- 26538391 TI - Coordinated Regulation of miR-155 and miR-146a Genes during Induction of Endotoxin Tolerance in Macrophages. AB - Endotoxin tolerance occurs to protect the organism from hyperactivation of innate immune responses, primarily mediated by macrophages. Regulation of endotoxin tolerance occurs at multiple levels of cell responses and requires significant changes in gene expression. In the process of macrophage activation, induced expression of microRNA (miR)-155 and miR-146a contributes to the regulation of the inflammatory response and endotoxin tolerance. In this article, we demonstrate that expression of both miRNAs is coordinately regulated during endotoxin tolerance by a complex mechanism that involves monoallelic interchromosomal association, alterations in histone methyl marks, and transcription factor binding. Upon activation of naive macrophages, Histone3 was trimethylated at lysine4 and NFkappaBp65 was bound on both miR-155 and miR-146a gene loci. However, at the stage of endotoxin tolerance, both miR gene loci were occupied by C/EBPbeta, NFkappaBp50, and the repressive Histone3 marks trimethylation of K9 of H3. DNA fluorescence in situ hybridization experiments revealed monoallelic interchromosomal colocalization of miR-155 and miR-146a gene loci at the stage of endotoxin tolerance, whereas RNA-DNA-fluorescence in situ hybridization experiments showed that the colocalized alleles were silenced, suggesting a common repression mechanism. Genetic ablation of Akt1, which is known to abrogate endotoxin tolerance, abolished induction of loci colocalization and C/EBPbeta binding, further supporting that this mechanism occurs specifically in endotoxin tolerance. Overall, this study demonstrates that two miRNAs are coordinately regulated via gene colocalization at the three-dimensional chromatin space, same transcriptional machinery, and similar Histone3 methylation profile, contributing to the development of endotoxin tolerance. PMID- 26538393 TI - Foxn1 Protein Expression in the Developing, Aging, and Regenerating Thymus. AB - The forkhead box N1 (Foxn1) protein is the key regulator of thymic epithelial cell (TEC) development, yet how Foxn1 functions remains largely unknown. All mature TECs arise from Foxn1-expressing progenitors/immature TECs and it is widely assumed that TECs as a whole are defined by Foxn1 expression. However, data on the Foxn1 protein are virtually lacking. In this study, we developed novel tools to visualize Foxn1 protein expression at single-cell resolution. We generated Foxn1 knock-in mice expressing a C-terminal hemagglutinin-tagged Foxn1 protein, and a cytometry-grade monoclonal anti-Foxn1 Ab. We evaluated Foxn1 expression patterns in TEC subsets and its dynamics during normal thymus development, aging, injury, and regeneration. Upon challenges, upregulation of Foxn1 was a common feature of thymus regeneration, but the timing of Foxn1 expression changed and the responding TEC subsets depended on the type of treatment. Whereas dexamethasone and recombinant human fibroblast growth factor 7 promoted expansion of Foxn1(+)Ly51(+)CD80(-) TECs, castration led to expansion of Foxn1(+)Ly51(-)CD80(+) TECs. Collectively, Foxn1 expression is highly heterogeneous in the normal thymus, with large fractions of Foxn1(low) or Foxn1( ) TECs accumulating with age. Furthermore, Foxn1 expression is responsive to perturbations. PMID- 26538392 TI - MicroRNA-15b/16 Enhances the Induction of Regulatory T Cells by Regulating the Expression of Rictor and mTOR. AB - CD4(+) regulatory T cells (Tregs) are essential for controlling immune responses and preventing autoimmunity. Their development requires regulation of gene expression by microRNAs (miRNAs). To understand miRNA function in Treg development, we searched for important miRNAs and their relevant target genes. Of the more abundantly expressed miRNAs in Tregs, only miR-15b/16, miR-24, and miR 29a impacted the production of in vitro-induced Tregs (iTregs) in overexpression and blocking experiments. miRNA mimics for these significantly enhanced the induction of iTregs in Dicer(-/-) CD4(+) T cells. Furthermore, the overexpression of miR-15b/16 in conventional CD4(+) T cells adoptively transferred into Rag2(-/ ) mice increased the in vivo development of peripheral Tregs and diminished the severity of autoimmune colitis. In searching for targets of miR-15b/16, we observed that the mammalian target of rapamycin (mTOR) signaling pathway was enhanced in Dicer(-/-) CD4(+) T cells, and its pharmacological inhibition restored induction of iTregs. Suppression of mTOR signaling is essential for induction of iTregs from naive CD4(+) T cells, and the mTORC2 component, Rictor, contained a functional target site for miR-15b/16. Rictor was more abundantly expressed in Dicer(-/-) T cells as was mTOR, and their expression was downregulated by the overexpression of miR-15b/16. This led to a reduction in mTOR signaling, as measured by phosphorylation of the downstream target, ribosomal protein S6. Finally, knockdown of Rictor by small interfering RNAs enhanced Treg induction in Dicer(-/-) CD4(+) T cells. Therefore, an important mechanism of miRNA regulation of Treg development is through regulation of the mTOR signaling pathway. PMID- 26538394 TI - A Novel Function for P2Y2 in Myeloid Recipient-Derived Cells during Graft-versus Host Disease. AB - Acute graft-versus-host disease (GvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation. During the initiation phase of acute GvHD, endogenous danger signals such as ATP are released and inform the innate immune system via activation of the purinergic receptor P2X7 that a noninfectious damage has occurred. A second ATP-activated purinergic receptor involved in inflammatory diseases is P2Y2. In this study, we used P2y2(-/-) mice to test the role of this receptor in GvHD. P2y2(-/-) recipients experienced reduced GvHD-related mortality, IL-6 levels, enterocyte apoptosis, and histopathology scores. Chimeric mice with P2y2 deficiency restricted to hematopoietic tissues survived longer after GvHD induction than did wild-type mice. P2y2 deficiency of the recipient was connected to lower levels of myeloperoxidase in the intestinal tract of mice developing GvHD and a reduced myeloid cell signature. Selective deficiency of P2Y2 in inflammatory monocytes decreased GvHD severity. Mechanistically, P2y2(-/-) inflammatory monocytes displayed defective ERK activation and reactive oxygen species production. Compatible with a role of P2Y2 in human GvHD, the frequency of P2Y2(+) cells in inflamed GvHD lesions correlated with histopathological GvHD severity. Our findings indicate a novel function for P2Y2 in ATP-activated recipient myeloid cells during GvHD, which could be exploited when targeting danger signals to prevent GvHD. PMID- 26538395 TI - DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation. AB - The NLRP3 inflammasome plays a major role in innate immune responses by activating caspase-1, resulting in secretion of IL-1beta and inflammatory pathologic responses. Viral RNA can induce NLRP3 inflammasome activation. However, none of the components of NLRP3 inflammasome has the ability to bind viral RNA. Therefore, it had been proposed that there might have been some unidentified cytosolic RNA sensors that could bind viral RNA and NLRP3 to initiate NLRP3 inflammasome activation. In this study, DDX19A, a member of the DEAD/H-box protein family, was identified as a novel component of NLRP3 inflammasome using arterivirus infection as a model. We found that DDX19A interacted with viral RNA and NLRP3. Knockdown of DDX19A expression efficiently inhibited procaspase-1 cleavage and IL-1beta secretion in porcine reproductive and respiration syndrome virus (PRRSV)-infected or PRRSV RNA-stimulated primary porcine alveolar macrophages. Overall, DDX19A was identified as a novel cytosolic RNA sensor that bridged PRRSV RNA and NLRP3 to activate NLRP3 inflammasome. PMID- 26538396 TI - IL-17A-Producing gammadelta T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver. AB - Intracellular infections, such as those caused by the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL), require a potent host proinflammatory response for control. IL-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. However, there are conflicting reports on the exact roles for IL-17 during parasitic infections and limited knowledge about cellular sources and the immune pathways it modulates. We examined the role of IL-17 in an experimental model of VL caused by infection of C57BL/6 mice with L. donovani and identified an early suppressive role for IL-17 in the liver that limited control of parasite growth. IL-17-producing gammadelta T cells recruited to the liver in the first week of infection were the critical source of IL-17 in this model, and CCR2(+) inflammatory monocytes were an important target for the suppressive effects of IL-17. Improved parasite control was independent of NO generation, but associated with maintenance of superoxide dismutase mRNA expression in the absence of IL-17 in the liver. Thus, we have identified a novel inhibitory function for IL-17 in parasitic infection, and our results demonstrate important interactions among gammadelta T cells, monocytes, and infected macrophages in the liver that can determine the outcome of parasitic infection. PMID- 26538397 TI - FLI1 Levels Impact CXCR3 Expression and Renal Infiltration of T Cells and Renal Glycosphingolipid Metabolism in the MRL/lpr Lupus Mouse Strain. AB - The ETS factor Friend leukemia virus integration 1 (FLI1) is a key modulator of lupus disease expression. Overexpressing FLI1 in healthy mice results in the development of an autoimmune kidney disease similar to that observed in lupus. Lowering the global levels of FLI1 in two lupus strains (Fli1(+/-)) significantly improved kidney disease and prolonged survival. T cells from MRL/lpr Fli1(+/-) lupus mice have reduced activation and IL-4 production, neuraminidase 1 expression, and the levels of the glycosphingolipid lactosylceramide. In this study, we demonstrate that MRL/lpr Fli1(+/-) mice have significantly decreased renal neuraminidase 1 and lactosylceramide levels. This corresponds with a significant decrease in the number of total CD3(+) cells, as well as CD4(+) and CD44(+)CD62L(-) T cell subsets in the kidney of MRL/lpr Fli1(+/-) mice compared with the Fli1(+/+) nephritic mice. We further demonstrate that the percentage of CXCR3(+) T cells and Cxcr3 message levels in T cells are significantly decreased and correspond with a decrease in renal CXCR3(+) cells and in Cxcl9 and Cxcl10 expression in the MRL/lpr Fli1(+/-) compared with the Fli1(+/+) nephritic mice. Our results suggest that reducing the levels of FLI1 in MRL/lpr mice may be protective against development of nephritis in part through downregulation of CXCR3, reducing renal T cell infiltration and glycosphingolipid levels. PMID- 26538399 TI - The attitudes of medical students in Europe toward the clinical importance of embryology. AB - Although there have been many studies reporting the attitudes of medical students to the clinical importance of gross anatomy, little is known about their opinions concerning the clinical importance of embryology. Using Thurstone and Chave methods to assess attitudes, nearly 1,600 medical students across Europe in the early stages of their training provided responses to a survey that tested the hypothesis that they do not regard embryology as highly clinically relevant. Indeed, we further proposed that student attitudes to gross anatomy are much more positive than those toward embryology. Our findings show that our hypotheses hold, regardless of the university and country surveyed and regardless of the teaching methods employed for embryology. Clearly, embryology has a significant part to play in medical education in terms of understanding prenatal life, of appreciating how the organization of the mature human body has developed, and of providing essential information for general medical practice, obstetrics and pediatrics, and teratology. However, while newly recruited medical students understand the importance of gross anatomy in the development of professional competence, understanding the importance of embryology requires teachers, medical educationalists, and devisors of medical curricula to pay special attention to informing students of the significant role played by embryology in attaining clinical competence and achieving the knowledge and understanding of the biomedical sciences that underpins becoming a learned member of a health care profession. PMID- 26538398 TI - Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen Induced Arthritis. AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-alpha, IL-17, and IL-1beta. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. PMID- 26538400 TI - Evaluation of methods for differential expression analysis on multi-group RNA-seq count data. AB - BACKGROUND: RNA-seq is a powerful tool for measuring transcriptomes, especially for identifying differentially expressed genes or transcripts (DEGs) between sample groups. A number of methods have been developed for this task, and several evaluation studies have also been reported. However, those evaluations so far have been restricted to two-group comparisons. Accumulations of comparative studies for multi-group data are also desired. METHODS: We compare 12 pipelines available in nine R packages for detecting differential expressions (DE) from multi-group RNA-seq count data, focusing on three-group data with or without replicates. We evaluate those pipelines on the basis of both simulation data and real count data. RESULTS: As a result, the pipelines in the TCC package performed comparably to or better than other pipelines under various simulation scenarios. TCC implements a multi-step normalization strategy (called DEGES) that internally uses functions provided by other representative packages (edgeR, DESeq2, and so on). We found considerably different numbers of identified DEGs (18.5 ~ 45.7% of all genes) among the pipelines for the same real dataset but similar distributions of the classified expression patterns. We also found that DE results can roughly be estimated by the hierarchical dendrogram of sample clustering for the raw count data. CONCLUSION: We confirmed the DEGES-based pipelines implemented in TCC performed well in a three-group comparison as well as a two-group comparison. We recommend using the DEGES-based pipeline that internally uses edgeR (here called the EEE-E pipeline) for count data with replicates (especially for small sample sizes). For data without replicates, the DEGES-based pipeline with DESeq2 (called SSS-S) can be recommended. PMID- 26538401 TI - Author's Reply: Hemidystonia caused by frontal cortical infarction. PMID- 26538402 TI - Erratum to: Mechanical endovascular thrombectomy for acute ischemic stroke: a retrospective multicenter study in Belgium. PMID- 26538403 TI - Solitary Langerhans cell histiocytosis of the cavernous sinus with orbital extension in an adult. PMID- 26538406 TI - Enhancing the Value of Free Metals in the Synthesis of Lanthanoid Formamidinates: Is a Co-oxidant Needed? AB - Treatment of N,N'-bis(aryl)formamidines (ArFormH), N,N'-bis(2,6 difluorophenyl)formamidine (DFFormH) or N,N'-bis(2,6 diisopropylphenyl)formamidine (DippFormH), with europium metal in CH3 CN is an efficient synthesis of the divalent complexes: [{Eu(DFForm)2 (CH3 CN)2 }2 ] (Eu1) or [Eu(DippForm)2 (CH3 CN)4 ] (Eu2). The synthetic method was extended to ytterbium, but the metal required activation by addition of Hg(0) . With DFFormH in CH3 CN, [{Yb(DFForm)2 (CH3 CN)}2 ] (Yb1) was obtained in good yield, and [Yb(DFForm)2 (thf)3 ] (Yb3) was obtained from a synthesis in CH3 CN/THF. Thus, this synthetic method completely circumvents the use of either salt metathesis, or redox transmetallation/protolysis (RTP) protocols to prepare divalent rare earth formamidinates. Heating Yb1 in PhMe/C6 D6 resulted in decomposition to trivalent products, including one from a CH3 CN activation process. For a synthetic comparison, divalent ytterbium DFForm and DippForm complexes were synthesised by RTP reactions between Yb(0) , Hg(R)2 (R=Ph, C6 F5 ), and ArFormH in THF, leading to the isolation of either [Yb(DFForm)2 (thf)3 ] (Yb3), or the first five coordinate rare-earth formamidinate complex [Yb(DippForm)2 (thf)] (Yb4 b), and, from adjustment of the stoichiometry, trivalent [Yb(DFForm)3 (thf)] (Yb6). Oxidation of Yb3 with benzophenone (bp), or halogenating agents (TiCl4 (thf)2 , Ph3 CCl, C2 Cl6 ) gave [Yb(DFForm)3 (bp)] or [Yb(DFForm)2 Cl(thf)2 ], respectively. Furthermore, the structural chemistry of divalent ArForm complexes has been substantially broadened. Not only have the highest and lowest coordination numbers for divalent rare-earth ArForm complexes been achieved in Eu2 and Yb4 b, respectively, but also dimeric Eu1 and Yb1 have highly unusual ArForm bridging coordination modes, either perpendicular MU 1kappa(N:N'):2kappa(N:N') in Eu1, or the twisted MU-1kappa(N:N'):2kappa(N':F') DFForm coordination in Yb1, both unprecedented in divalent rare-earth ArForm chemistry and in the wider divalent rare-earth amidinate field. PMID- 26538404 TI - Altered morphological dynamics of activated microglia after induction of status epilepticus. AB - BACKGROUND: Microglia cells are the resident macrophages of the central nervous system and are considered its first line of defense. In the normal brain, their ramified processes are highly motile, constantly scanning the surrounding brain tissue and rapidly moving towards sites of acute injury or danger signals. These microglial dynamics are thought to be critical for brain homeostasis. Under pathological conditions, microglial cells undergo "activation," which modifies many of their molecular and morphological properties. Investigations of the effects of activation on motility are limited and have given mixed results. In particular, little is known about how microglial motility is altered in epilepsy, which is characterized by a strong inflammatory reaction and microglial activation. METHODS: We used a mouse model of status epilepticus induced by kainate injections and time-lapse two-photon microscopy to image GFP-labeled microglia in acute hippocampal brain slices. We studied how microglial activation affected the motility of microglial processes, including basal motility, and their responses to local triggering stimuli. RESULTS: Our study reveals that microglial motility was largely preserved in kainate-treated animals, despite clear signs of microglial activation. In addition, whereas the velocities of microglial processes during basal scanning and towards a laser lesion were unaltered 48 h after status epilepticus, we observed an increase in the size of the territory scanned by single microglial processes during basal motility and an elevated directional velocity towards a pipette containing a purinergic agonist. CONCLUSIONS: Microglial activation differentially impacted the dynamic scanning behavior of microglia in response to specific acute noxious stimuli, which may be an important feature of the adaptive behavior of microglia during pathophysiological conditions. PMID- 26538405 TI - A microbiological assay to estimate the antimicrobial activity of parenteral tildipirosin against foodborne pathogens and commensals in the colon of beef cattle and pigs. AB - Tildipirosin (TIP) is a novel 16-membered-ring macrolide authorized for the treatment of bovine and swine respiratory disease. The pH dependency of macrolide antimicrobial activity is well known. Considering that the pH in the colon contents of growing beef cattle and pigs is usually below pH 7.0, the minimum inhibitory concentrations (MIC) of TIP against foodborne bacterial pathogens such as Campylobacter (C.) coli, C. jejuni and Salmonella enterica and commensal species including Enterococcus (E.) faecalis, E. faecium and Escherichia coli were determined under standard (pH 7.3 +/- 1) or neutral as well as slightly acidic conditions. A decrease in pH from 7.3 to 6.7 resulted in an increase in MICs of TIP. Except for the MICs > 256 MUg/mL observed in the resistant subpopulation of the C. coli and the Enterococcus species, the MIC ranges increased from 2-8 MUg/mL to 64-> 256 MUg/mL for Salmonella enterica and E. coli, from 8-16 MUg/mL to 32-128 MUg/mL for the two Campylobacter species, and from 4 32 MUg/mL to 128-> 256 MUg/mL for both Enterococcus species. To estimate the antimicrobial activity of TIP in the colon contents of livestock during recommended usage of the parenterally administered TIP (Zuprevo((r)) ), and to compare this with the increased MICs at the slightly acidic colonic pH, we developed and validated a microbiological assay for TIP and used this to test incurred faecal samples collected from cattle and pigs. Microbiological activity of luminal TIP was determined in aqueous supernatants from diluted faeces, using standard curves produced from TIP-spiked faecal supernatants. The limit of quantification (LOQ) for TIP was 1 MUg/mL (ppm). In a cattle study (n = 14), 3 of 28 faecal samples collected 24 and 48 h post-treatment were found to contain TIP above the LOQ (concentrations of 1.3-1.8 ppm). In another cattle study (n = 12) with faecal samples collected at 8, 24 and 48 h post-treatment, TIP concentrations were above the LOQ in 4 of the 8 h samples (1.2-2.6 ppm) and one of the 24-h samples (1.3 ppm). In a pig study (n = 12) with faecal samples collected 24, 48 and 72 h post-treatment, only one sample contained TIP above the LOQ (concentration 1.5 ppm). In another pig study (n = 12), with samples collected at 8, 24 48 and 96 h post-treatment, TIP concentrations were above the LOQ in one 8-h sample (1.1 ppm) and two 24-h samples (2.3 and 2.5 ppm). None of the 48-h and 96-h samples from these 4 studies contained measurable TIP concentrations. Thus, in cattle and pigs, only a small fraction of faecal samples collected up to 24 h postdosing contained measurable microbiologically active TIP, with its maximum limited to 2.6 MUg/mL. This is several log2 dilution steps below the MICs of TIP against foodborne pathogens and commensals collected under acidic conditions comparable with those in the colonic contents and may explain a lack of intestinal dysbacteriosis with parenteral tildipirosin in livestock. PMID- 26538407 TI - Addressing Psychometric Limitations of the Difficulties in Emotion Regulation Scale Through Item Modification. AB - Through its frequent use, a pattern has emerged showing psychometric limitations of the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004). This 3-part study sought to (a) determine whether these limitations are due to a method effect by rewording all reverse-coded items in a straightforward manner and submitting them to exploratory factor analysis (EFA), and (b) examine the tenability of an adaptation of the original measure. EFA results from Study 1 (N = 743) supported retention of 29 modified items across 5 factors. Consistent with the original theoretical underpinnings of the DERS, Awareness and Clarity items loaded on the same factor. In Study 2 (N = 738), confirmatory factor analysis (CFA) was used to examine the factor structure of the pool of items identified in Study 1. All of the modified subscales clustered strongly with one another and evidenced large loadings on a higher-order emotion regulation construct. These results were replicated in Study 3 (N = 918). Results from Study 3 also provided support for the reliability and validity of scores on the modified version of the DERS (i.e., internal consistency, convergent and criterion-related validity). These findings provide psychometric support for a modified version of the DERS. PMID- 26538408 TI - A systematic review and network meta-analysis comparing the use of Foley catheters, misoprostol, and dinoprostone for cervical ripening in the induction of labour. AB - BACKGROUND: Various methods are used for cervical ripening during the induction of labour. It is still debatable which of these methods of treatment is optimal. OBJECTIVE: To compare treatment techniques for cervical ripening in the induction of labour. SEARCH STRATEGY: Medline, Embase, and the Cochrane Collaboration databases were searched using the keywords 'cervical ripening', 'labour induced', 'misoprostol', 'dinoprostone', and 'Foley catheter'. SELECTION CRITERIA: Randomised controlled trials (RCTs) of cervical ripening during the induction of labour, evaluating rates of failure to achieve vaginal delivery within 24 hours, incidence of uterine hyperstimulation with fetal heart rate (FHR) changes, and rates of caesarean section. Studies including women with prelabour rupture of membranes were excluded. DATA COLLECTION AND ANALYSIS: Outcome data were collected and analysed through pairwise meta-analysis and network meta-analysis within a Bayesian framework. MAIN RESULTS: A total of 96 RCTs (17,387 women) were included in the meta-analysis. Vaginal misoprostol was the most effective cervical ripening method to achieve vaginal delivery within 24 hours, but had the highest incidence of uterine hyperstimulation with FHR changes. The use of a Foley catheter to induce labour was associated with the lowest rate of uterine hyperstimulation accompanied by FHR changes. The caesarean section rate was lowest using oral misoprostol for the induction of labour. AUTHOR'S CONCLUSIONS: No method of labour induction demonstrated overall superiority when considering all three clinical outcomes. Decisions regarding the choice of induction method will depend upon the relative preference for effecting vaginal delivery within 24 hours, minimising the incidence of uterine hyperstimulation with adverse FHR changes and avoiding caesarean section. TWEETABLE ABSTRACT: Oral misoprostol for the induction of labour is safer than vaginal misoprostol and has the lowest rate of caesarean section. PMID- 26538409 TI - Bicornuate Uterus and Situs Inversus. PMID- 26538410 TI - Robotic Surgery in Women With Ovarian Cancer: Surgical Technique and Evidence of Clinical Outcomes. AB - Robotic surgery is a new technology that has been progressively implemented to treat endometrial and cervical cancer. However, the use of robotic surgery for ovarian cancer is limited to a few series of cases and comparative studies with laparoscopy or laparotomy. The technical issues concerning robotic surgery, as well as clinical evidence, are described in this review. Robotic surgery in early stage, advanced stage, and relapsed ovarian cancer is discussed separately. In conclusion, evidence regarding the use of robotic-assisted surgical treatment for women with ovarian cancer is still scarce, but its use is progressively growing. Robotic-assisted staging in selected patients with early stage disease has an important role in referral institutions when well-trained gynecologists perform surgeries. However, minimally invasive surgery in patients with advanced stage or relapsed ovarian cancer requires further investigation, even in selected cases. PMID- 26538411 TI - Pursed-lips breathing reduces dynamic hyperinflation induced by activities of daily living test in patients with chronic obstructive pulmonary disease: A randomized cross-over study. AB - BACKGROUND: Dynamic hyperinflation leads to dyspnoea and consequent limitations in functional capacity in chronic obstructive pulmonary disease. It has been shown that the response to pursed-lips breathing in terms of dynamic hyperinflation and lower-limb exercise capacity is variable, and its effects on activities of daily living are unknown. This study aimed to evaluate the effect of pursed-lips breathing on dynamic hyperinflation and functional capacity in patients with chronic obstructive pulmonary disease in a lower-limb exercise test and in a multiple-task activities of daily living test. DESIGN: Randomized cross over study. PATIENTS: Twenty-five patients with chronic obstructive pulmonary disease (16 men, mean age 64 +/- 7 years, forced expiratory volume in 1 s (FEV1) = 41.7 +/- 14.7% predicted). METHODS: Patients randomly performed two 6-min walk tests (6MWT) with and without pursed-lips breathing (6MWT(PLB) and 6MWT(Non-PLB)) and two Glittre-ADL tests with and without pursed-lips breathing (TGlittre(PLB) and TGlittre(Non-PLB)). Inspiratory capacity was assessed at baseline and immediately after the tests. RESULTS: The 6MWT(Non-PLB) and TGlittre(Non-PLB) induced similar magnitude dynamic hyperinflation (0.22 +/- 0.24 l and 0.31 +/- 0.23 l, respectively; p > 0.05). Pursed-lips breathing did not improve dynamic hyperinflation induced by the 6MWT (0.24 +/- 0.20 and 0.22 +/- 0.24 l, respectively, with and without pursed-lips breathing; p > 0.05). Dynamic hyperinflation in the TGlittre(PLB) was significantly lower than in the TGlittre(Non-PLB) (0.19 +/- 0.20 l and 0.31 +/- 0.23 l, respectively; p = 0.02). Pursed-lips breathing did not improve 6MWT or TGlittre performance. CONCLUSION: Pursed-lips breathing reduced dynamic hyperinflation in the TGlittre, but not in the 6MWT. However, pursed-lips breathing did not improve functional capacity. PMID- 26538412 TI - Measurement of Capillary Radius and Contact Angle within Porous Media. AB - The pore radius (i.e., capillary radius) and contact angle determine the capillary pressure generated in a porous medium. The most common method to determine these two parameters is through measurement of the capillary pressure generated by a reference liquid (i.e., a liquid with near-zero contact angle) and a test liquid. The rate of rise technique, commonly used to determine the capillary pressure, results in significant uncertainties. In this study, we utilize a recently developed technique for independently measuring the capillary pressure and permeability to determine the equivalent minimum capillary radii and contact angle of water within micropillar wick structures. In this method, the experimentally measured dryout threshold of a wick structure at different wicking lengths is fit to Darcy's law to extract the maximum capillary pressure generated by the test liquid. The equivalent minimum capillary radii of different wick geometries are determined by measuring the maximum capillary pressures generated using n-hexane as the working fluid. It is found that the equivalent minimum capillary radius is dependent on the diameter of pillars and the spacing between pillars. The equivalent capillary radii of micropillar wicks determined using the new method are found to be up to 7 times greater than the current geometry-based first-order estimates. The contact angle subtended by water at the walls of the micropillars is determined by measuring the capillary pressure generated by water within the arrays and the measured capillary radii for the different geometries. This mean contact angle of water is determined to be 54.7 degrees . PMID- 26538414 TI - Bioavailability of lutein in corn distillers dried grains with solubles relative to lutein in corn gluten meal based on lutein retention in egg yolk. AB - BACKGROUND: Dietary lutein and its food sources have gained great attention due to its health-promoting effects on humans, especially for certain eye diseases. However, relative bioavailability (RBV) of lutein among lutein-rich feed ingredients that lead to lutein-enriched egg production has not been determined. Thus, the RBV of lutein in corn distillers dried grains with solubles (DDGS) as compared to lutein in corn gluten meal (CGM) was evaluated based on lutein retention in egg yolk. RESULTS: Increasing inclusion levels of DDGS or CGM in diets increased (linear, P < 0.01) Roche colour score and lutein concentrations of egg yolk without affecting laying performance. Multiple regression analysis revealed that the bioavailability of lutein in DDGS was less (P < 0.05) than that of lutein in CGM, with the RBV of lutein in DDGS being 61.6% when the bioavailability of lutein in CGM was assumed to be 100% for lutein retention in egg yolk. CONCLUSION: The results of the present experiment indicate that the DDGS can be a potential ingredient for laying hens to improve egg yolk colour and lutein concentrations of egg yolk although lutein in DDGS is less bioavailable than lutein in CGM. (c) 2015 Society of Chemical Industry. PMID- 26538416 TI - Time-Dependent Resolution of Collagen Deposition During Skin Repair in Rats: A Correlative Morphological and Biochemical Study. AB - Skin samples were used to compare microscopy methods used to quantify collagen with potential applicability to resolve time-dependent collagen deposition during skin wound healing in rats. Skin wounds by secondary intention were made in rats and tissue fragments were collected every 7 days for 21 days. Collagen content determined by biochemical analysis was compared with collagen measured by point counting (PC) on histological skin sections stained by Gomori's trichrome method (Trichrome/PC), Sirius red under polarized light (PL) microscopy (Sirius red/PL PC), and computational color segmentation (CS) applied to sections stained with Sirius red (Sirius red/PL-CS). All microscopy methods investigated resolved the time-dependent dynamics of collagen deposition in scar tissue during skin wound healing in rats. Collagen content measured by Sirius red/PL-PC and Sirius red/PL CS was significantly lower when compared with Trichrome/PC. The Trichrome/PC method provided overestimated values of collagen compared with biochemical analysis. In the early stages of wound healing, which shows high production of noncollagenous molecules, Sirius red/PL-CS and Sirius red/PL-PC methods were more suitable for quantification of collagen fibers. Trichrome staining did not allow clear separation between collagenous and noncollagenous elements in skin samples, introducing a marked bias in collagen quantification. PMID- 26538415 TI - Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma. AB - Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are liver originated malignant tumors. Of the two, ICC has the worse prognosis because it has no reliable diagnostic markers and its carcinogenic mechanism is not fully understood. The aim of this study was to integrate metabolomics and transcriptomics datasets to identify variances if any in the carcinogenic mechanism of ICC and HCC. Ten ICC and 6 HCC who were resected surgically, were enrolled. miRNA and mRNA expression analysis were performed by microarray on ICC and HCC and their corresponding non-tumor tissues (ICC_NT and HCC_NT). Compound analysis was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Principle component analysis (PCA) revealed that among the four sample groups (ICC, ICC_NT, HCC, and HCC_NT) there were 14 compounds, 62 mRNAs and 17 miRNAs with two distinct patterns: tumor and non-tumor, and ICC and non-ICC. We accurately (84.38%) distinguished ICC by the distinct pattern of its compounds. Pathway analysis using transcriptome and metabolome showed that several pathways varied between tumor and non-tumor samples. Based on the results of the PCA, we believe that ICC and HCC have different carcinogenic mechanism therefore knowing the specific profile of genes and compounds can be useful in diagnosing ICC. PMID- 26538418 TI - When gain-of-function research is not "gain-of-function" research. PMID- 26538417 TI - Myc coordinates transcription and translation to enhance transformation and suppress invasiveness. AB - c-Myc is one of the major human proto-oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc-induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript-specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFbeta pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc-induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells. PMID- 26538419 TI - Occurrence of Norovirus GIV in Environmental Water Samples from Belem City, Amazon Region, Brazil. AB - Noroviruses are the major cause of non-bacterial acute gastroenteritis outbreaks in humans, with few reports about the occurrence of the norovirus GIV strain. We investigated the presence of norovirus GIV in surface water (river, bay, and stream) and untreated sewage, and we determined a positivity rate of 9.4% (9/96). The strains genotyped were GIV.1. To our knowledge, this is the first report of GIV in Brazil. PMID- 26538420 TI - Environmental Surveillance of Polioviruses in Rio de Janeiro, Brazil, in Support to the Activities of Global Polio Eradication Initiative. AB - Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period. PMID- 26538421 TI - The "silent" imprint of musical training. AB - Playing a musical instrument at a professional level is a complex multimodal task requiring information integration between different brain regions supporting auditory, somatosensory, motor, and cognitive functions. These kinds of task specific activations are known to have a profound influence on both the functional and structural architecture of the human brain. However, until now, it is widely unknown whether this specific imprint of musical practice can still be detected during rest when no musical instrument is used. Therefore, we applied high-density electroencephalography and evaluated whole-brain functional connectivity as well as small-world topologies (i.e., node degree) during resting state in a sample of 15 professional musicians and 15 nonmusicians. As expected, musicians demonstrate increased intra- and interhemispheric functional connectivity between those brain regions that are typically involved in music perception and production, such as the auditory, the sensorimotor, and prefrontal cortex as well as Broca's area. In addition, mean connectivity within this specific network was positively related to musical skill and the total number of training hours. Thus, we conclude that musical training distinctively shapes intrinsic functional network characteristics in such a manner that its signature can still be detected during a task-free condition. Hum Brain Mapp 37:536-546, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26538422 TI - Do we need to lower the cut point of the 2010 ACR/EULAR classification criteria for diagnosing rheumatoid arthritis? AB - OBJECTIVE: In this study we aimed to evaluate the effect of lowering the cut point of the 2010 criteria to identify more patients with RA among early inflammatory arthritis patients. METHODS: We included early arthritis patients from the Rotterdam Early Arthritis Cohort with at least one joint with clinical synovitis and symptoms for <1 year, with no other explanation for their symptoms. The demographic and clinical characteristics of each patient were recorded at baseline. Patients were classified as case or non-case at the 1-year follow-up by the definition used in the development of the 2010 criteria (MTX initiation). To assess the diagnostic performance of the 2010 criteria, the sensitivity and specificity at each cut point were determined. RESULTS: We included 557 patients in our analysis. At the 1-year follow-up, 253 patients (45%) were classified as case (MTX use). In the group of patients who scored 0-5 points (n = 328), 98 patients (30%) were classified as case (MTX use). The sensitivity and specificity of the 2010 criteria using the cut point of 6 were 61% and 76%, respectively. With the cut point of 5, the sensitivity would increase to 76% and the specificity would decrease to 68%. CONCLUSION: By lowering the cut point of the 2010 criteria from 6 to 5 points, we were able to identify 15% more RA patients at the cost of 8% more false-positive patients. PMID- 26538424 TI - Multimodal treatment for malignant pleural mesothelioma. PMID- 26538423 TI - Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. AB - BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54.2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55.9 Gy (IQR 46.8-56.0). Median locoregional relapse-free survival from surgery, was 7.6 months (95% CI 4.5-10.7) in the no radiotherapy group and 9.4 months (6.5 11.9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly. PMID- 26538425 TI - Detection of cardiovascular risk from a photoplethysmographic signal using a matching pursuit algorithm. AB - Cardiovascular disease is the main cause of death in Europe, and early detection of increased cardiovascular risk (CR) is of clinical importance. Pulse wave analysis based on pulse oximetry has proven useful for the recognition of increased CR. The current study provides a detailed description of the pulse wave analysis technology and its clinical application. A novel matching pursuit-based feature extraction algorithm was applied for signal decomposition of the overnight photoplethysmographic pulse wave signals obtained by a single-pulse oximeter sensor. The algorithm computes nine parameters (pulse index, SpO2 index, pulse wave amplitude index, respiratory-related pulse oscillations, pulse propagation time, periodic and symmetric desaturations, time under 90 % SpO2, difference between pulse and SpO2 index, and arrhythmia). The technology was applied in 631 patients referred for a sleep study with suspected sleep apnea. The technical failure rate was 1.4 %. Anthropometric data like age and BMI correlated significantly with measures of vascular stiffness and pulse rate variability (PPT and age r = -0.54, p < 0.001, PR and age r = -0.36, p < 0.01). The composite biosignal risk score showed a dose-response relationship with the number of CR factors (p < 0.001) and was further elevated in patients with sleep apnea (AHI >= 15n/h; p < 0.001). The developed algorithm extracts meaningful parameters indicative of cardiorespiratory and autonomic nervous system function and dysfunction in patients suspected of SDB. PMID- 26538426 TI - Parameters for novel incus replacement prostheses. AB - Prostheses replacing the incus in its normal position and equipped with two joints might transfer sound as effectively as the intact ossicular chain and allow adjustment to quasi-static pressure changes. A prerequisite for prostheses development is the access to dimensions and distances of the ossicular chain which are necessary to conceptualize shape and size. Fifteen cadaveric human temporal bone specimens were investigated by means of micro-CT followed by 3D analysis. Each specimen was scanned three times: after removal of incus, after additional removal of the malleus head, and after approaching the umbo to the promontory. Artificial umbo medialization as a surrogate for quasi-static pressure changes leads to relevant variations in the distance between the upper part of the malleus and the stapes. Prostheses replacing the incus in its normal position should be equipped with a sliding ball joint or similar construction to allow adjustment to quasi-static pressure changes. PMID- 26538427 TI - Comparison of two different steroid treatments with hyperbaric oxygen for idiopathic sudden sensorineural hearing loss. AB - The purpose of the study was to assess the efficacy of the association of intratympanic (IT) steroid and hyperbaric oxygen (HBO) therapy in patients presenting with idiopathic sudden sensorineural hearing loss (ISSNHL), and to compare this protocol with another consisting of intravenous (IV) steroid administration and HBO therapy. A total of 80 patients diagnosed with ISSNHL were included in this prospective trial. Patients were divided into three categories: a mild-to-moderate ISSNHL group with a pure-tone average (PTA) <=60 decibels (dB), a severe ISSNHL group with a PTA of 60-80 dB, and a profound ISSNHL group with a PTA >=81 dB. The first protocol consisted of 20 sessions of HBO therapy together with IV methylprednisolone 1 mg/kg body weight and a 10 mg taper every 3 days for 10 days. The second protocol consisted of HBO therapy for 20 sessions, together with an IT injection of dexamethasone at a dose of 4 mg/mL, 0.5-0.7 mL once a day for 7 consecutive days, performed 3 h before the HBO therapy. In the mild-to-moderate ISSNHL patients, the mean hearing gain and successful treatment rate was 19 (0-27) dB and 78.9 %, respectively in the IT + HBO treatment group, and 18 (3-44) dB and 70.5 % in the IV + HBO therapy group. In the severe ISSNHL patients, the mean hearing gain and successful treatment rate was 33 (1-54) dB and 81.8 %, respectively in the IT + HBO treatment group and 33.5 (7-57) dB and 58.2 % in the IV + HBO group. In the profound ISSNHL patients, the mean hearing gain and successful treatment rate was 36 (4-69) dB and 40 %, respectively in the IT + HBO therapy group, and 39.5 (0-92) dB and 72.7 % in the IV + HBO treatment group. The results demonstrated that patients with severe hearing loss success rate was superior in the group submitted to IT + HBO treatment, conversely IV + HBO therapy may be benefit for patients with profound hearing loss. Nevertheless, these clinical results were not statistically significant. PMID- 26538428 TI - Genotype-guided therapy improves initial acenocoumarol dosing. Results from a prospective randomised study. AB - A few trials so far have evaluated the effectiveness of algorithms designed to calculate doses in oral anticoagulant therapy, with negative or contradictory results. We compared a genotype-guided algorithm vs physician management for the initiation of acenocoumarol. In a two-arm, prospective, randomised study with patients with atrial fibrillation who started therapy, the first dose was administered to all patients according to the physician's criteria. At 72 hours, the corresponding dose was calculated based on INR in the standard care group (SC, N=92), whereas genetic data (VKORC1, CYP2C9 and CYP4F2) were also considered for the genotype-guided dosing (pharmacogenetic) group (PGx, N=87) by using an algorithm previously validated in 2,683 patients. The primary outcomes were: patients with steady dose, the time needed to reach the same and the percentage of therapeutic INRs. After 90 days, 25% of the SC and 39% of the PGx patients reached the steady dose (p=0.038). Kaplan-Meier analysis showed that PGx group needed fewer days to reach therapeutic INR (p=0.033). Additionally, PGx had a higher percentage of therapeutic INRs than SC patients (50% and 45%, respectively) (p=0.046). After six months the proportion of steadily anticoagulated patients remained significantly higher in PGx (p=0.010). In conclusion, genotype-guided dosing was associated with a higher percentage of patients with steady dose than routine practice when starting oral anticoagulation with acenocoumarol. PMID- 26538429 TI - The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila. AB - Neurons require target-derived autocrine and paracrine growth factors to maintain proper identity, innervation, homeostasis and survival. Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here, we review recent findings from the Drosophila larval neuromuscular junction (NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, particularly in the bone morphogenic protein, Wingless and c-Jun activated kinase pathways, regulating elaboration and stability of NMJ arbors, construction of synapses and synaptic transmission and homeostasis. These membrane trafficking and signaling pathways have been implicated in human motor neuron diseases including amyotrophic lateral sclerosis and hereditary spastic paraplegia, highlighting their importance for neuronal health and survival. PMID- 26538430 TI - How to talk to someone with an "untreatable" lifelong condition. PMID- 26538431 TI - An Efficient and Economical Assay to Screen for Triclosan Binding to FabI. AB - Triclosan is an effective inhibitor for enoyl acyl carrier protein reductase (ENR) in fatty acid biosynthesis. Triclosan-resistant mutants of ENR have emerged. Thus, it is important to detect these triclosan-resistant mutations in ENR. Generally, enzyme activity assays on the mutants are used to determine the effect of triclosan on ENR activity. Since the substrates are linked to acyl carrier protein (ACP), the assays are challenging due to the need to prepare the ACP and link it to the substrates. Non-ACP-linked (coenzyme A [CoA]-linked) substrates can be used in some ENR, but not in all. Consequently, screening for triclosan-resistant mutants is also challenging. We have developed a simple thermal shift assay, which does not use ACP-linked substrates, to determine the binding ability of triclosan to the ENR active site, and thus it can be used for screening for triclosan-resistant mutants. Staphylococcus aureus FabI enzyme and its mutants were used to demonstrate the binding ability of triclosan with NADP(+) to FabI. The direct correlation between the binding ability and enzyme activity was demonstrated with Francisella tularensis FabI. This method may also be applied to select effective triclosan analogues that inhibit ENR activity. PMID- 26538433 TI - Standardized quantitative sensory testing in patients with psoriasis vulgaris: evidence for altered large and small fibre functioning. PMID- 26538432 TI - Discovery and Characterization of a Biologically Active Non-ATP-Competitive p38 MAP Kinase Inhibitor. AB - Mitogen-activated protein kinase (MAPK) p38 is part of a broad and ubiquitously expressed family of MAPKs whose activity is responsible for mediating an intracellular response to extracellular stimuli through a phosphorylation cascade. p38 is central to this signaling node and is activated by upstream kinases while being responsible for activating downstream kinases and transcription factors via phosphorylation. Dysregulated p38 activity is associated with numerous autoimmune disorders and has been implicated in the progression of several types of cancer. A number of p38 inhibitors have been tested in clinical trials, with none receiving regulatory approval. One characteristic shared by all of the compounds that failed clinical trials is that they are all adenosine triphosphate (ATP)-competitive p38 inhibitors. Seeing this lack of mechanistic diversity as an opportunity, we screened ~32,000 substances in search of novel p38 inhibitors. Among the inhibitors discovered is a compound that is both non-ATP competitive and biologically active in cell-based models for p38 activity. This is the first reported discovery of a non-ATP-competitive p38 inhibitor that is active in cells and, as such, may enable new pharmacophore designs for both therapeutic and basic research to better understand and exploit non-ATP-competitive inhibitors of p38 activity. PMID- 26538434 TI - Authors' reply to Minisola and colleagues, Kausar, and Sharvill. PMID- 26538435 TI - Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice. AB - Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. PMID- 26538436 TI - Real-time monitoring of NKCC2 endocytosis by total internal reflection fluorescence (TIRF) microscopy. AB - The apical Na-K-2Cl cotransporter (NKCC2) mediates NaCl reabsorption by the thick ascending limb (TAL). The amount of NKCC2 at the apical membrane of TAL cells is determined by exocytic delivery, recycling, and endocytosis. Surface biotinylation allows measurement of NKCC2 endocytosis, but it has low time resolution and does not allow imaging of the dynamic process of endocytosis. We hypothesized that total internal reflection fluorescence (TIRF) microscopy imaging of labeled NKCC2 would allow monitoring of NKCC2 endocytosis in polarized Madin-Darby canine kidney (MDCK) and TAL cells. Thus we generated a NKCC2 construct containing a biotin acceptor domain (BAD) sequence between the transmembrane domains 5 and 6. Once expressed in polarized MDCK or TAL cells, surface NKCC2 was specifically biotinylated by exogenous biotin ligase (BirA). We also demonstrate that expression of a secretory form of BirA in TAL cells induces metabolic biotinylation of NKCC2. Labeling biotinylated surface NKCC2 with fluorescent streptavidin showed that most apical NKCC2 was located within small discrete domains or clusters referred to as "puncta" on the TIRF field. NKCC2 puncta were observed to disappear from the TIRF field, indicating an endocytic event which led to a decrease in the number of surface puncta at a rate of 1.18 +/- 0.16%/min in MDCK cells, and a rate 1.09 +/- 0.08%/min in TAL cells (n = 5). Treating cells with a cholesterol-chelating agent (methyl-beta-cyclodextrin) completely blocked NKCC2 endocytosis. We conclude that TIRF microscopy of labeled NKCC2 allows the dynamic imaging of individual endocytic events at the apical membrane of TAL cells. PMID- 26538437 TI - Mini-review: diabetic renal complications, a potential stinky remedy. AB - Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in diabetic patients. Despite optimal management, a significant number of patients progress toward end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini-review highlights the recent findings on the role of H2S in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow-releasing H2S compounds and its therapeutic potential is also included. PMID- 26538439 TI - Mesenchymal stem cells and chronic renal artery stenosis. AB - Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss, and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed. PMID- 26538438 TI - The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules. AB - Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2-mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H(+) exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4 yl)amino]ethanaminium (NBD-MTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [(3)H]1-methyl-4 phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 MUM bafilomycin (BAF), an inhibitor of V-type H(+)-ATPase, and accumulation of [(3)H]MPP and [(3)H]NBD-MTMA was reduced by >30% by coexposure with 5 MUM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H(+)-ATPase. The accumulation of [(3)H]MPP by isolated single nonperfused rabbit RPTs was also reduced >30% by coexposure to 5 MUM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [(3)H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 MUM BAF, suggesting that vesicles loaded with OCs(+) are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion. PMID- 26538440 TI - Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis. AB - Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 +/- 3 vs. 87 +/- 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 +/- 2 vs. 5 +/- 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 +/- 3 mmHg) and salt sensitivity (5 +/- 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function. PMID- 26538442 TI - An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney. AB - We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease. PMID- 26538441 TI - Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases. AB - MicroRNAs (miRNA) are endogenously produced short noncoding regulatory RNAs that can repress gene expression by posttranscriptional mechanisms. They can therefore influence both normal and pathological conditions in diverse biological systems. Several miRNAs have been detected in kidneys, where they have been found to be crucial for renal development and normal physiological functions as well as significant contributors to the pathogenesis of renal disorders such as diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and others, due to their effects on key genes involved in these disease processes. miRNAs have also emerged as novel biomarkers in these renal disorders. Due to increasing evidence of their actions in various kidney segments, in this mini review we discuss the functional significance of altered miRNA expression during the development of renal pathologies and highlight emerging miRNA-based therapeutics and diagnostic strategies for early detection and treatment of kidney diseases. PMID- 26538443 TI - The role of pendrin in blood pressure regulation. AB - Pendrin is a Na(+)-independent Cl(-)/HCO3(-) exchanger found in the apical regions of type B and non-A, non-B intercalated cells within the aldosterone sensitive region of the nephron, i.e., the distal convoluted tubule (DCT), the connecting tubule (CNT), and the cortical collecting duct (CCD). Type B intercalated cells mediate Cl(-) absorption and HCO3(-) secretion primarily through pendrin-mediated Cl(-)/HCO3(-) exchange. This exchanger is upregulated with angiotensin II administration and in models of metabolic alkalosis, such as following administration of aldosterone or NaHCO3. In the absence of pendrin mediated HCO3(-) secretion, an enhanced alkalosis is observed following aldosterone or NaHCO3 administration. However, probably of more significance is the role of pendrin in the pressor response to aldosterone. Pendrin mediates Cl( ) absorption and modulates aldosterone-induced Na(+) absorption mediated by the epithelial Na channel (ENaC). Pendrin changes ENaC activity by changing both channel open probability (Po) and surface density (N), at least partly by altering luminal HCO3(-) and ATP concentration. Thus aldosterone and angiotensin II stimulate pendrin expression and function, which stimulates ENaC activity, thereby contributing to the pressor response of these hormones. However, pendrin may modulate blood pressure partly through its extrarenal effects. For example, pendrin is expressed in the adrenal medulla, where it modulates catecholamine release. The increase in catecholamine release observed with pendrin gene ablation likely contributes to the increment in vascular contractile force observed in the pendrin null mouse. This review summarizes the signaling mechanisms that regulate pendrin abundance and function as well as the contribution of pendrin to distal nephron function. PMID- 26538444 TI - Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6) dependent mechanism in an insect model of calcium oxalate nephrolithiasis. AB - Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization. PMID- 26538445 TI - MRI shines (radiofrequency) light on kidney physiology. PMID- 26538446 TI - Fullerene-free small molecule organic solar cells with a high open circuit voltage of 1.15 V. AB - A new small molecule named DTBTF with thiobarbituric acid as a terminal group was designed and synthesized as an acceptor for organic photovoltaic applications. DTBTF exhibits strong absorption in the visible region, and a relatively high lying LUMO energy level (-3.62 eV). All-small-molecule organic solar cells based on DR3TSBDT:DTBTF blend films show a considerable PCE of 3.84% with a high V(oc) of 1.15 V. PMID- 26538447 TI - Revisiting operons: an analysis of the landscape of transcriptional units in E. coli. AB - BACKGROUND: Bacterial operons are considerably more complex than what were thought. At least their components are dynamically rather than statically defined as previously assumed. Here we present a computational study of the landscape of the transcriptional units (TUs) of E. coli K12, revealed by the available genomic and transcriptomic data, providing new understanding about the complexity of TUs as a whole encoded in the genome of E. coli K12. RESULTS AND CONCLUSION: Our main findings include that (i) different TUs may overlap with each other by sharing common genes, giving rise to clusters of overlapped TUs (TUCs) along the genomic sequence; (ii) the intergenic regions in front of the first gene of each TU tend to have more conserved sequence motifs than those of the other genes inside the TU, suggesting that TUs each have their own promoters; (iii) the terminators associated with the 3' ends of TUCs tend to be Rho-independent terminators, substantially more often than terminators of TUs that end inside a TUC; and (iv) the functional relatedness of adjacent gene pairs in individual TUs is higher than those in TUCs, suggesting that individual TUs are more basic functional units than TUCs. PMID- 26538449 TI - Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice. AB - Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction, isolated areas of interest, and insistence on sameness. Mutations in Phosphatase and tensin homolog missing on chromosome 10 (PTEN) have been reported in individuals with ASDs. Recent evidence highlights a crucial role of the cerebellum in the etiopathogenesis of ASDs. In the present study we analyzed the specific contribution of cerebellar Purkinje cell (PC) PTEN loss to these disorders. Using the Cre-loxP recombination system, we generated conditional knockout mice in which PTEN inactivation was induced specifically in PCs. We investigated PC morphology and physiology as well as sociability, repetitive behavior, motor learning, and cognitive inflexibility of adult PC PTEN mutant mice. Loss of PTEN in PCs results in autistic-like traits, including impaired sociability, repetitive behavior and deficits in motor learning. Mutant PCs appear hypertrophic and show structural abnormalities in dendrites and axons, decreased excitability, disrupted parallel fiber and climbing fiber synapses and late-onset cell death. Our results unveil new roles of PTEN in PC function and provide the first evidence of a link between the loss of PTEN in PCs and the genesis of ASD-like traits. PMID- 26538450 TI - Change in incidence of clinic visits for all-cause and rotavirus gastroenteritis in young children following the introduction of universal rotavirus vaccination in Israel. AB - Both rotavirus vaccines RotaTeq and Rotarix were efficacious against severe rotavirus gastroenteritis in clinical trials; yet real-world data on the effect of rotavirus vaccines on mild to moderate disease are limited. We used a large computerised database of Maccabi Health Services Health Maintenance Organisation (HMO), the second largest HMO in Israel covering 25% of the Israeli population, to compare the incidence of acute gastroenteritis (AGE) clinic visits in community settings (n=302,445) before (2005-10) and after (2011-13) the introduction of universal rotavirus immunisation in Israel. We retrieved laboratory results of rotavirus antigen tests (n=18,133) and using a weighted analysis, we estimated the impact of rotavirus immunisation on the disease burden of rotavirus AGE clinic visits. Following the introduction of universal rotavirus immunisation, the typical winter peaks of rotavirus AGE were substantially lower and significant reductions of 14.8% (95% confidence interval (CI): 13.5-16.1) in all-cause AGE clinic visits and of 59.7% (95% CI: 59.8-62.6) in rotavirus AGE clinic visits were observed. The decrease was observed in all age groups, but it was greater in children aged 0 to 23 months than those aged 24 to 59 months. Continued rotavirus laboratory surveillance is warranted to monitor the sustainability of these changes. PMID- 26538448 TI - Overexpression of Forebrain CRH During Early Life Increases Trauma Susceptibility in Adulthood. AB - Although early-life stress is a significant risk factor for developing anxiety disorders, including posttraumatic stress disorder (PTSD), the underlying mechanisms are unclear. Corticotropin releasing hormone (CRH) is disrupted in individuals with PTSD and early-life stress and hence may mediate the effects of early-life stress on PTSD risk. We hypothesized that CRH hyper-signaling in the forebrain during early development is sufficient to increase response to trauma in adulthood. To test this hypothesis, we induced transient, forebrain-specific, CRH overexpression during early-life (pre-puberty, CRHOEdev) in double-mutant mice (Camk2a-rtta2 * tetO-Crh) and tested their behavioral and gene expression responses to the predator stress model of PTSD in adulthood. In one cohort of CRHOEdev exposed and unexposed mice, avoidance and arousal behaviors were examined 7-15 days after exposure to predator stress. In another cohort, gene expression changes in Crhr1, Crhr2, and Fkbp51 in forebrain of CRHOEdev exposed and unexposed mice were examined 7 days after predator stress. CRHOEdev induced robust increases in startle reactivity and reductions in startle inhibition independently of predator stress in both male and female mice. Avoidance behaviors after predator stress were highly dependent on sex and CRHOEdev exposure. Whereas stressed females exhibited robust avoidance responses that were not altered by CRHOEdev, males developed significant avoidance only when exposed to both CRHOEdev and stress. Quantitative real-time-PCR analysis indicated that CRHOEdev unexposed males exhibit significant changes in Crhr2 expression in the amygdala and bed nucleus stria terminalis in response to stress, whereas males exposed to CRHOEdev did not. Similar to CRHOEdev males, females exhibited no significant Crhr2 gene expression changes in response to stress. Cortical Fkbp51 expression was also significantly reduced by stress and CRHOEdev exposure in males, but not in females. These findings indicate that forebrain CRH hyper signaling in early-life is sufficient to increase enduring effects of adult trauma and attenuate Crhr2 expression changes in response to stress in males. These data support growing evidence for significant sex differences in response to trauma, and support further study of CRHR2 as a candidate mechanism for PTSD risk. PMID- 26538451 TI - Emergence of Hemagglutinin Mutations During the Course of Influenza Infection. AB - Influenza remains a significant cause of disease mortality. The ongoing threat of influenza infection is partly attributable to the emergence of new mutations in the influenza genome. Among the influenza viral gene products, the hemagglutinin (HA) glycoprotein plays a critical role in influenza pathogenesis, is the target for vaccines and accumulates new mutations that may alter the efficacy of immunization. To study the emergence of HA mutations during the course of infection, we employed a deep-targeted sequencing method. We used samples from 17 patients with active H1N1 or H3N2 influenza infections. These patients were not treated with antivirals. In addition, we had samples from five patients who were analyzed longitudinally. Thus, we determined the quantitative changes in the fractional representation of HA mutations during the course of infection. Across individuals in the study, a series of novel HA mutations directly altered the HA coding sequence were identified. Serial viral sampling revealed HA mutations that either were stable, expanded or were reduced in representation during the course of the infection. Overall, we demonstrated the emergence of unique mutations specific to an infected individual and temporal genetic variation during infection. PMID- 26538453 TI - Choosing and using non-steroidal anti-inflammatory drugs in haemophilia. AB - The management of pain and inflammation in haemophilic arthropathy is challenging due to the lack of anti-inflammatory analgesic agents perfectly suitable for this population. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of arthritis due to their analgesic and anti-inflammatory effects. Their use in persons with haemophilia (PWH), however, is limited due to increased risk of bleeding mainly from the upper gastrointestinal (UGI) tract. Cyclooxygenase-2 (COX-2) selective NSAIDs which have comparable analgesic effect to traditional NSAIDs (tNSAIDs) but with less UGI bleeding have been considered to be a suitable option for treatment of haemophilic arthropathy. COX-2 inhibitors, however, have an increased in the risk of cardiovascular (CV) disease. Although the atherosclerotic burden in PWH is similar to that in the general population, the risk of CV-related deaths is lower. PWH have a higher risk of GI bleeding and lower risk of thrombotic disease compared to general population. Therefore, when PWH require anti-inflammatory/analgesic agents, it seems reasonable to use lowest dose of COX-2 inhibitors for the shortest period together with a proton pump inhibitor. Helicobacter pylori infection should be tested for and eradicated prior to starting NSAID treatment in PWH. Furthermore, regular blood pressure and renal function test monitoring is required during COX 2 inhibitor treatment. PMID- 26538452 TI - Mutual and asynchronous anticipation and action in sports as globally competitive and locally coordinative dynamics. AB - Humans interact by changing their actions, perceiving other's actions and executing solutions in conflicting situations. Using oscillator models, nonlinear dynamics have been considered for describing these complex human movements as an emergence of self-organisation. However, these frameworks cannot explain the hierarchical structures of complex behaviours between conflicting inter-agent and adapting intra-agent systems, especially in sport competitions wherein mutually quick decision making and execution are required. Here we adopt a hybrid multiscale approach to model an attack-and-defend game during which both players predict the opponent's movement and move with a delay. From both simulated and measured data, one synchronous outcome between two-agent (i.e. successful defence) can be described as one attractor. In contrast, the other coordination breaking outcome (i.e. successful attack) cannot be explained using gradient dynamics because the asymmetric interaction cannot always assume a conserved physical quantity. Instead, we provide the asymmetric and asynchronous hierarchical dynamical models to discuss two-agent competition. Our framework suggests that possessing information about an opponent and oneself in local coordinative and global-competitive scale enables us to gain a deeper understanding of sports competitions. We anticipate developments in the scientific fields of complex movement adapting to such uncontrolled environments. PMID- 26538454 TI - Hypothyroidism Induces Hypophagia Associated with Alterations in Protein Expression of Neuropeptide Y and Proopiomelanocortin in the Arcuate Nucleus, Independently of Hypothalamic Nuclei-Specific Changes in Leptin Signaling. AB - BACKGROUND: Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood. It has been shown that hypothyroid rats exhibited impaired leptin anorexigenic effect and signaling in total hypothalamus, even though they were hypophagic. It was hypothesized that hypothyroidism modulates the expression of neuropeptides: orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC), independently of inducing nuclei-specific changes in hypothalamic leptin signaling. METHODS: Adult male rats were rendered hypothyroid by administration of 0.03% methimazole in the drinking water for 21 days. Protein content of NPY, POMC, and leptin signaling (the signal transducer and activator of transcription 3 [STAT3] pathway) were evaluated by Western blot, and mRNA levels by real time reverse transcription polymerase chain reaction in arcuate (ARC), ventromedial (VMN), and paraventricular (PVN) hypothalamic nuclei isolated from euthyroid (eu) and hypothyroid (hypo) rats. Leptin anorexigenic effect was tested by recording food intake for two hours after intracerebroventricular (i.c.v.) administration of leptin. Statistical differences were considered significant at p <= 0.05. RESULTS: Hypothyroidism was confirmed by decreased serum triiodothyronine, thyroxine, and increased thyrotropin, in addition to increased levels of pro-TRH mRNA in PVN and Dio2 mRNA in the ARC of hypo rats. Hypothyroidism decreased body weight and food intake associated with decreased protein content of NPY and increased content of POMC in the ARC. Conversely, hypothyroidism induced central resistance to the acute anorexigenic effect of leptin, since while euthyroid rats displayed reduced food intake after leptin i.c.v. injection, hypothyroid rats showed no response. Hypothyroid rats exhibited decreased leptin receptor (ObRb) protein content in ARC and VMN but not in PVN nucleus. ObRb protein changes were concomitant with decreased phosphorylated STAT3 in the ARC, and decreased total STAT3 in VMN and PVN. However, hypothyroidism did not affect mRNA levels of Lepr or Stat3 in the hypothalamic nuclei. CONCLUSIONS: Experimental hypothyroidism induced a negative energy balance accompanied by decreased NPY and increased POMC protein content in the ARC, resulting in predominance of anorexigenic pathways, despite central leptin resistance and impairment of the leptin signaling cascade in a nuclei-specific manner. PMID- 26538455 TI - Mass immunization with inactivated polio vaccine in conflict zones--Experience from Borno and Yobe States, North-Eastern Nigeria. AB - The use of Inactivated Polio Vaccine (IPV) in routine immunization to replace Oral Polio Vaccine (OPV) is crucial in eradicating polio. In June 2014, Nigeria launched an IPV campaign in the conflict-affected states of Borno and Yobe, the largest ever implemented in Africa. We present the initiatives and lessons learned. The 8-day event involved two parallel campaigns. OPV target age was 0-59 months, while IPV targeted all children aged 14 weeks to 59 months. The Borno state primary health care agency set up temporary health camps for the exercise and treated minor ailments for all. The target population for the OPV campaign was 685,674 children in Borno and 113,774 in Yobe. The IPV target population for Borno was 608,964 and for Yobe 111,570. OPV coverage was 105.1 per cent for Borno and 103.3 per cent for Yobe. IPV coverage was 102.9 per cent for Borno and 99.1 per cent for Yobe. (Where we describe coverage as greater than 100 per cent, this reflects original underestimates of the target populations.) A successful campaign and IPV immunization is viable in conflict areas. PMID- 26538456 TI - Patterns of sexual behaviors among unmarried adolescents and youth in three Asian cities. AB - We examined patterns of sexual behaviors of unmarried adolescents and youth (UAY) in three Asian cities (Shanghai, Taipei, and Hanoi) and identified factors related to the timing of initial sexual experience. From analysis of a sample of 16,554 UAY aged 15-24 years recruited from Shanghai, Taipei, and Hanoi plus data collected from face-to-face interviews complemented by computer-assisted self interviews for intimate questions, we learned: UAY in Shanghai, Taipei, and Hanoi have different sexual behaviors. Affluent economic status increases the likelihood of early initial sexual experiences. Higher educational attainment may delay initial intercourse. Compared with Shanghai UAY, study participants from Taipei and Hanoi were 3.64 times and 0.33 times as likely to participate intercourse. These data can provide a basis for developing effective government policies and social interventions. PMID- 26538458 TI - Origin of exotic ferromagnetic behavior in exfoliated layered transition metal dichalcogenides MoS2 and WS2. AB - Bulk layered transition metal dichalcogenides (TMDs) show diamagnetic properties. When exfoliated, the materials' band gap increases and changes from an indirect band gap to a direct one. During the exfoliation, the TMDs may undergo a phase transition from 2H to 1T polymorph, which is likely electronically driven and accompanied by a metal-insulator transition. A significantly higher efficiency of the exfoliation was observed using sodium naphthalenide compared to butyllithium. Moreover we demonstrate that the exfoliation has a dramatic influence on the magnetic properties of two TMDs, MoS2 and WS2. These materials become partly ferromagnetic upon exfoliation, which is a highly unexpected behavior. Exotic ferromagnetism is generally observed on samples with a high degree of exfoliation, which indicates the association of this effect with defects formed on the edges of dichalcogenide sheets. Such an exotic ferromagnetic behavior, if properly understood and brought under material engineering control, shall open the door to new applications of these materials. PMID- 26538457 TI - Reaching out: junctions between cardiac telocytes and cardiac stem cells in culture. AB - Telocytes (TCs) were previously shown by our group to form a tandem with stem/progenitor cells in cardiac stem cell (CSC) niches, fulfilling various roles in cardiac renewal. Among these, the ability to 'nurse' CSCs in situ, both through direct physical contact (junctions) as well as at a distance, by paracrine signalling or through extracellular vesicles containing mRNA. We employed electron microscopy to identify junctions (such as gap or adherens junctions) in a co-culture of cardiac TCs and CSCs. Gap junctions were observed between TCs, which formed networks, however, not between TCs and CSCs. Instead, we show that TCs and CSCs interact in culture forming heterocellular adherens junctions, as well as non-classical junctions such as puncta adherentia and stromal synapses. The stromal synapse formed between TCs and CSCs (both stromal cells) was frequently associated with the presence of electron-dense nanostructures (on average about 15 nm in length) connecting the two opposing membranes. The average width of the synaptic cleft was 30 nm, whereas the average length of the intercellular contact was 5 MUm. Recent studies have shown that stem cells fail to adequately engraft and survive in the hostile environment of the injured myocardium, possibly as a result of the absence of the pro regenerative components of the secretome (paracrine factors) and/or of neighbouring support cells. Herein, we emphasize the similarities between the junctions described in co-culture and the junctions identified between TCs and CSCs in situ. Reproducing a CSC niche in culture may represent a viable alternative to mono-cellular therapies. PMID- 26538460 TI - Fano resonance assisting plasmonic circular dichroism from nanorice heterodimers for extrinsic chirality. AB - In this work, the circular dichroisms (CD) of nanorice heterodimers consisting of two parallel arranged nanorices with the same size but different materials are investigated theoretically. Symmetry-breaking is introduced by using different materials and oblique incidence to achieve strong CD at the vicinity of Fano resonance peaks. We demonstrate that all Au-Ag heterodimers exhibit multipolar Fano resonances and strong CD effect. A simple quantitative analysis shows that the structure with larger Fano asymmetry factor has stronger CD. The intensity and peak positions of the CD effect can be flexibly tuned in a large range by changing particle size, shape, the inter-particle distance and surroundings. Furthermore, CD spectra exhibit high sensitivity to ambient medium in visible and near infrared regions. Our results here are beneficial for the design and application of high sensitive CD sensors and other related fields. PMID- 26538459 TI - Genetic evidence of a recent Tibetan ancestry to Sherpas in the Himalayan region. AB - Sherpas living around the Himalayas are renowned as high-altitude mountain climbers but when and where the Sherpa people originated from remains contentious. In this study, we collected DNA samples from 582 Sherpas living in Nepal and Tibet Autonomous Region of China to study the genetic diversity of both their maternal (mitochondrial DNA) and paternal (Y chromosome) lineages. Analysis showed that Sherpas share most of their paternal and maternal lineages with indigenous Tibetans, representing a recently derived sub-lineage. The estimated ages of two Sherpa-specific mtDNA sub-haplogroups (C4a3b1 and A15c1) indicate a shallow genetic divergence between Sherpas and Tibetans less than 1,500 years ago. These findings reject the previous theory that Sherpa and Han Chinese served as dual ancestral populations of Tibetans, and conversely suggest that Tibetans are the ancestral populations of the Sherpas, whose adaptive traits for high altitude were recently inherited from their ancestors in Tibet. PMID- 26538461 TI - Preliminary results of proton beam therapy combined with weekly cisplatin intra arterial infusion via a superficial temporal artery for treatment of maxillary sinus carcinoma. AB - OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS: Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra arterial infusion chemotherapy with cisplatin. RESULTS: The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with 0.05). CONCLUSION: Decontamination by water and air spray, etching, and bonding was effective in restoring the bond strength of silorane-based composite increments. PMID- 26538475 TI - Ring-opening polymerization of rac-lactide mediated by tetrametallic lithium and sodium diamino-bis(phenolate) complexes. AB - Lithium and sodium compounds supported by tetradentate amino-bis(phenolato) ligands, [Li2(N2O2(BuBuPip))] (1), [Na2(N2O2(BuBuPip))] (2) (where [N2O2(BuBuPip)] = 2,2'-N,N'-homopiperazinyl-bis(2-methylene-4,6-tert butylphenol), and [Li2(N2O2(BuMePip))] (3), [Na2(N2O2(BuMePip))] (4) (where [N2O2(BuMePip)] = 2,2'-N,N'-homopiperazinyl-bis(2-methylene-4-methyl-6-tert butylphenol) were synthesized and characterized by NMR spectroscopy and MALDI-TOF mass spectrometry. Variable temperature NMR experiments were performed to understand solution-phase dynamics. The solid-state structures of 1 and 4 were determined by X-ray diffraction and reveal tetrametallic species. PGSE NMR spectroscopic data suggests that 1 maintains its aggregated structure in CD2Cl2. The complexes exhibit good activity for controlled ring-opening polymerization of rac-lactide (LA) both solvent free and in solution to yield PLA with low dispersities. Stoichiometric reactions suggest that the formation of PLA may proceed by the typical coordination-insertion mechanism. For example, (7)Li NMR experiments show growth of a new resonance when 1 is mixed with 1 equiv. LA and (1)H NMR data suggests formation of a Li-alkoxide species upon reaction of 1 with BnOH. PMID- 26538476 TI - First detection of Leishmania major DNA in Sergentomyia (Sintonius) clydei (Sinton, 1928, Psychodidae: Phlebotominae), from an outbreak area of cutaneous leishmaniasis in Tunisia. AB - In recent years there has been growing interest in Sergentomyia species. Their role in the spread of mammalian leishmaniasis appears repeatedly in the literature and the possibility of its implication in Leishmania transmission to humans remains controversial. Sergentomyia (Sintonius) clydei is one of several cryptic species sharing therefore common morphologic criteria with others species of the subgenera Sintonius. Little is known about this specie in Tunisia. We sampled and identified different specimens including four specimens of S. clydei collected from Sidi Bouzid and Kairouan areas (center of Tunisia) using morphological tools. Male Sergentomyia clydei and Sergentomyia christophersi are known to share several morphological characters and can be mistaken for. Consequently we took advantage of 5 male S. christophersi available in our collection (Tataouin, South of Tunisia). In our study morphological tools were completed by molecular study of cytochrome b gene to identify S. clydei. For the detection of Leishmania spp. that might infect our specimens, Leishmania DNA was analyzed by amplification of kinetoplast minicircle DNA using real-time PCR and nested-PCR. Obtained result was confirmed by restriction analysis of the amplified ribosomal internal transcribed spacer 1 (ITS1). We provide in our study, the first molecular identification of S. clydei, in Tunisia. Our Neighbor Joining tree based on mitochondrial cytochrome b gene shows two different clusters. The first includes the Tunisians S. clydei and other specimens from Africa, Middle East and the Arabic peninsula, and the second cluster containing the specimens from Seychelle. Unexpectedly, we also demonstrate the infection of one anthropophilic female S. clydei by Leishmania major DNA. This finding shows that more attention should be paid when identifying parasites by molecular tools within sandfly vector. PMID- 26538478 TI - Sports participation after rehabilitation: Barriers and facilitators. AB - OBJECTIVE: To analyse barriers to, and facilitators of, sports participation among people with physical disabilities after rehabilitation and to compare differences between inactive and active participants regarding these experienced barriers and facilitators. METHODS: Participants were 1,223 adults (mean age 51.6 years, standard deviation 15.1 years) treated in the Rehabilitation Centre of the University Medical Center Groningen, who completed a questionnaire. The questionnaire consisted of a self-constructed questionnaire regarding barriers and facilitators. RESULTS: Fifty-eight percent of the participants were active in sports after their rehabilitation. Younger age and a higher level of education were positively associated with sports participation, whereas using assistive devices and experiencing environmental barriers were negatively associated. Facilitators of sports participation were health, fun and increasing physical strength, and advice from rehabilitation professionals. CONCLUSION: Rehabilitation professionals should emphasize the health benefits of, and enjoyment from, sports participation for people with physical disabilities. They should repeatedly remind people with physical disabilities to stay/become active after completing their rehabilitation programme. Rehabilitation professionals should also provide information about strategies to reduce environmental barriers to sports participation, which could help people using assistive devices to overcome these barriers. PMID- 26538477 TI - Short-term weight loss with diet and physical activity in young adults: The IDEA study. AB - OBJECTIVE: This study examined the effect of a behavioral weight loss intervention (BWLI) on young adults (age = 18-35 years). METHODS: Participants (N = 470) enrolled in a 6-month BWLI that included weekly group sessions, a prescribed energy-restricted diet, and moderate to vigorous physical activity (MVPA). Assessments included weight, body composition, fitness, lipids, glucose, insulin, resting blood pressure and heart rate, physical activity, and dietary intake. Data are presented as median [25th, 75th percentiles]. RESULTS: Retention was 90% (N = 424; age: 30.9 [27.8, 33.7] years; BMI: 31.2 [28.4, 34.3] kg m(-2) ). Participants completed 87.5% [76.1%, 95.5%] of scheduled intervention contacts. Weight and body fat decreased while fitness increased (P < 0.0001). MVPA in bouts >=10 min increased (P < 0.0001), though total MVPA did not change significantly. Sedentary time decreased (P = 0.03). Energy and percent fat intake decreased, while percent carbohydrate and protein intake increased (P < 0.0001). Systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, triglycerides, glucose, and insulin decreased (P < 0.0001). CONCLUSIONS: A 6 month BWLI produced favorable changes in dietary intake and physical activity and elicited favorable changes in weight and other health outcomes in young adults. MVPA performed in bouts of >=10 min was associated with greater weight loss, but sedentary behavior was not. PMID- 26538479 TI - White light emission and optical gains from a Si nanocrystal thin film. AB - We report a Si nanocrystal thin film consisting of free-standing Si nanocrystals, which can emit white light and show positive optical gains for its red, green and blue (RGB) components under ultraviolet excitation. Si nanocrystals with phi = 2.31 +/- 0.35 nm were prepared by chemical etching of Si powder, followed by filtering. After being mixed with SiO2 sol-gel and thermally annealed, a broadband photoluminescence (PL) from the thin film was observed. The RGB ratio of the PL can be tuned by changing the annealing temperature or atmosphere, which is 1.00/3.26/4.59 for the pure white light emission. The origins of the PL components could be due to differences in oxygen-passivation degree for Si nanocrystals. The results may find applications in white-light Si lasing and Si lighting. PMID- 26538480 TI - Is it oral or vaginal; and should it be misoprostol or dinoprostone for cervical ripening? How to interpret a network meta-analysis. PMID- 26538481 TI - Drivers of high-involvement consumers' intention to buy PDO wines: Valpolicella PDO case study. AB - BACKGROUND: This study investigates whether different sensory profiles of wines belonging to the same Protected Designation of Origin (PDO) are perceived as different products by consumers. It identifies the drivers of consumers' intention to buy preferred wines. Descriptive sensory analysis, consumer tests and consumer interviews were conducted to reach research aims. To perform the consumer tests and interviews, 443 consumers participated in the survey. The tasted wines comprised five samples representative of Valpolicella PDO wine. Analysis of variance tests, principal component analysis and linear and logit regressions were employed to verify the research hypotheses. RESULTS: The results demonstrated: (1) different sensory profiles exist within the Valpolicella PDO wine; (2) these sensory profiles result in consumers having the perception of diversified products; (3) the perception of differences was less marked for consumers than for trained assessors due to the different weight attributed to visual, aroma and the taste/mouthfeel hedonic dimensions; and (4) consumers' liking, as well as general perceptions, attitudes, preferences, wine knowledge and experience, contribute to consumers' intentions to buy more than the socio demographic characteristics of consumers. CONCLUSION: The analysis of the drivers of consumers' intention to buy certain PDO wines provides new marketing insights into the roles of intrinsic quality, preferences and consumers' subjective characteristics in market segmentation. (c) 2015 Society of Chemical Industry. PMID- 26538482 TI - Insights into immune responses in oral cancer through proteomic analysis of saliva and salivary extracellular vesicles. AB - The development and progression of oral cavity squamous cell carcinoma (OSCC) involves complex cellular mechanisms that contribute to the low five-year survival rate of approximately 20% among diagnosed patients. However, the biological processes essential to tumor progression are not completely understood. Therefore, detecting alterations in the salivary proteome may assist in elucidating the cellular mechanisms modulated in OSCC and improve the clinical prognosis of the disease. The proteome of whole saliva and salivary extracellular vesicles (EVs) from patients with OSCC and healthy individuals were analyzed by LC-MS/MS and label-free protein quantification. Proteome data analysis was performed using statistical, machine learning and feature selection methods with additional functional annotation. Biological processes related to immune responses, peptidase inhibitor activity, iron coordination and protease binding were overrepresented in the group of differentially expressed proteins. Proteins related to the inflammatory system, transport of metals and cellular growth and proliferation were identified in the proteome of salivary EVs. The proteomics data were robust and could classify OSCC with 90% accuracy. The saliva proteome analysis revealed that immune processes are related to the presence of OSCC and indicate that proteomics data can contribute to determining OSCC prognosis. PMID- 26538483 TI - Cp*Co(IPr): synthesis and reactivity of an unsaturated Co(i) complex. AB - Synthesis of coordinatively unsaturated Cp*Co(IPr) (2), is accomplished by addition of free N-heterocyclic carbene IPr to [(Cp*Co)2-MU-(eta(4):eta(4) toluene)] (1). Stoichiometric reactivity is consistent with a 16 electron species, as 2 undergoes ligand addition/NHC displacement and reversible reaction with dihydrogen. Cp*Co(IPr) represents an elusive example of a stable Cp*CoL fragment. PMID- 26538484 TI - Does the effect of pelleting depend on the wheat sample when fed to chickens? AB - Experimental comparisons of the nutritional value of different wheat cultivars commonly use feeds in meal form even though the large-scale broiler producers use steam pelleted feeds. The aim of this experiment was to examine the effect of steam pelleting on the performance, dietary N-corrected apparent metabolisable energy (AMEn), total tract dry matter retention (DMR), nitrogen retention (NR) and fat digestibility (FD) coefficients, and digestive tract development of broilers fed four different wheat samples in complete diets. Four European wheat samples, with different chemical composition and endosperm characteristics, were used in a broiler experiment. The wheat samples were milled through a 5 mm screen and four basal feeds containing 670 g/kg of each selected wheat sample were mixed. The basal feeds were then split into two batches and one of them was steam pelleted resulting in eight experimental diets. Each diet was fed ad libitum to eight pens of two male Ross 308 broilers from 10 to 24 days of age. Feeding pelleted diets improved (P0.05). Feeding different wheat types and pelleting did not (P>0.05) change the development of the gastrointestinal tract of the birds. The study showed that there were differences between four wheat samples when they were fed in pelleted complete feed, but no differences were observed when fed in mash form complete diets. Research on the interaction between pelleting and wheat chemical and quality characteristics is warranted. PMID- 26538486 TI - Prevalence of aggressive behaviours among inpatients with psychiatric disorders: A case study analysis from Jordan. AB - In this study, we investigated the correlates of aggression among consumers with mental illness within two psychiatric hospitals in Jordan. This was a descriptive, cross sectional study carried out by auditing consumers' medical records in regards to incidents of aggression before and during admission. Approval was gained from 203 next of kins to review the consumers' medical records. Results from this case analysis, found the prevalence of aggressive behaviours among psychiatric inpatient's in Jordan to be 23.6%, the most common form of aggression was consumer to consumer and that the aggressive act was more likely to be perpetrated by younger consumers. Such findings contribute to the discourse about aggression and understanding who and what causes aggression can go toward identify strategies for early intervention and management. After all, mental health units should be places of safety, that is, an asylum, and everyone who enters that environment deserves to be safe. PMID- 26538487 TI - The effects of cavity-filling techniques on microleakage in class II resin restorations prepared with Er:YAG laser and diamond bur: A scanning electron microscopy study. AB - The purpose of this study was to investigate how two cavity-filling techniques affect microleakage in class II resin restorations prepared with Er:YAG laser and diamond bur. Standard MO and DO cavities were prepared in 20 extracted third molars, each randomly assigned to either Group-1 [Herculite XRV Ultra-bur prepared cavity(bp)], Group-2 [Herculite XRV Ultra-laser-prepared cavity(lp)], Group-3 (SonicFill-(bp)], or Group-4 [SonicFill-(lp)]. For Groups 2 and 4, cavities were prepared by using an Er:YAG laser with a wavelength of 2.94 MUm, output power of 200 mJ/pulse, and repetition rate of 20Hz. Teeth were restored with a one-step, self-etch adhesive material (OptiBond All-in-One), a nanohybrid composite (Herculite XRV Ultra), and a bulk-fill composite (SonicFill) according to the manufacturer's instructions. Five teeth from each group were chosen for microleakage investigation and two teeth for scanning electron microscope evaluation. Statistical analysis was performed by using Kruskal-Wallis test. Pair wise comparisons were performed by Mann-Whitney U test with Bonferroni correction (p < 0.05). The statistical analysis of data revealed greater microleakage in cervical versus occlusal regions in all groups (P < 0.05). Group-2 yielded a higher degree of marginal leakage than Group-3 in terms of occlusal surfaces (p < 0.05). For cervical regions, a statistically significant difference was observed between Groups 2 and 3 as well as Groups 2 and 4 (p < 0.05). Group-3 exhibited significantly better marginal sealing than Group-1 in the cervical region (p < 0.05). The cavities prepared using an Er:YAG laser showed greater microleakage than those conventionally prepared using burs regardless of restorative material at both occlusal and cervical margins. SCANNING 38:389-395, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26538489 TI - Interferometry as a tool for evaluating effects of antimicrobial doses on Mycobacterium bovis growth. AB - Interferometry was used together with the conventional microplate resazurin assay to evaluate the antimycobacterial properties of essential oil (EO) from fruits of Pterodon emarginatus and also of rifampicin against Mycobacterium bovis. The aim of this work is not only to investigate the potential antimycobacterial activity of this EO, but also to test the interferometric method in comparison with the conventional one. The Minimum Inhibitory Concentration (MIC) values of EO (625 MUg/mL) and rifampicin (4 ng/mL) were firstly identified with the microplate method. These values were used as parameters in Drug Susceptibility Tests (DST) with interferometry. The interferometry confirmed the MIC value of EO identified with microplate and revealed a bacteriostatic behavior for this concentration. At 2500 MUg/mL interferometry revealed bactericidal activity of the EO. Mycobacterial growth was detected with interferometry at 4 ng/mL of rifampicin and even at higher concentrations. One important difference is that the interferometric method preserves the sample, so that after weeks of quantitative observation, the sample can be used to evaluate the bactericidal activity of the tested drug. PMID- 26538488 TI - Heritability of complex white matter diffusion traits assessed in a population isolate. AB - INTRODUCTION: Diffusion weighted imaging (DWI) methods can noninvasively ascertain cerebral microstructure by examining pattern and directions of water diffusion in the brain. We calculated heritability for DWI parameters in cerebral white (WM) and gray matter (GM) to study the genetic contribution to the diffusion signals across tissue boundaries. METHODS: Using Old Order Amish (OOA) population isolate with large family pedigrees and high environmental homogeneity, we compared the heritability of measures derived from three representative DWI methods targeting the corpus callosum WM and cingulate gyrus GM: diffusion tensor imaging (DTI), the permeability-diffusivity (PD) model, and the neurite orientation dispersion and density imaging (NODDI) model. These successively more complex models represent the diffusion signal modeling using one, two, and three diffusion compartments, respectively. RESULTS: We replicated the high heritability of the DTI-based fractional anisotropy (h(2) = 0.67) and radial diffusivity (h(2) = 0.72) in WM. High heritability in both WM and GM tissues were observed for the permeability-diffusivity index from the PD model (h(2) = 0.64 and 0.84), and the neurite density from the NODDI model (h(2) = 0.70 and 0.55). The orientation dispersion index from the NODDI model was only significantly heritable in GM (h(2) = 0.68). CONCLUSION: DWI measures from multicompartmental models were significantly heritable in WM and GM. DWI can offer valuable phenotypes for genetic research; and genes thus identified may reveal mechanisms contributing to mental and neurological disorders in which diffusion imaging anomalies are consistently found. Hum Brain Mapp 37:525-535, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26538490 TI - An Efficient Ion-Pair Liquid Chromatographic Method for the Determination of Some H2 Receptor Antagonists. AB - A simple, efficient and reliable ion-pair chromatography (IPC) method was developed and validated for the determination of some H2 receptor antagonists including ranitidine (RAN), nizatidine (NIZ) and famotidine (FAM). The use of IPC separations provided improved peak resolution with good peak shape in short analysis time and augmented method selectivity compared with the frequently used RP-C18 methods. A simple isocratic mode with mobile phase containing acetonitrile and 20 mM acetate buffer (50 : 50, v/v) containing 20 mM sodium dodecyl sulfate was used for separation. The flow rate was set at 1.0 mL min(-1), and the effluent was monitored by UV detector at 280 nm FAM and 320 nm for NIZ and RAN. The method was validated in accordance with International Conference on Harmonization guidelines and shown to be suitable for intended applications. The limits of detections and quantitations were 0.008-0.011 and 0.025-0.033 ug mL( 1), respectively. The proposed IPC method was successfully applied for the determination of pharmaceutical dosage forms without prior need for separation. Additionally, the developed method was applied for the determination of RAN in rabbit plasma using NIZ as the internal standard. The method entailed direct injection of the plasma samples after deproteination using methanol. Finally, the proposed IPC method was applied successfully in a pharmacokinetic study for RAN in rabbits after a single oral dose of RAN. PMID- 26538491 TI - Volatile Profile of Herniaria fontanesii Growing Spontaneously in Tunisia. AB - The essential oil extracted from Desfontaine's rupturewort, Herniaria fontanesii J. Gay subsp. fontanesii growing wildly in Tunisia, was analyzed using GC and GC MS techniques. The free radical scavenging capacity and total phenol contents of three crude extracts having different polarities (n-hexane, ethyl acetate and methanol) were examined. Thus, a total of 35 constituents were identified in the Desfontaine's rupturewort essential oil representing 89.8% of the whole constituents. The oil was dominated by hexadecanoic acid, caryophyllene oxide, terpin-4-ol, khusimone and trans-sabinene hydrate. The total phenolic contents ranged from 16.91 to 92.27 mg of gallic acid/g of dry weight and they were found to be significantly higher in methanol than in polar ethyl acetate and hexane extracts. Correlations were observed between the phenolic contents and the antioxidant properties. Thus, the antioxidant activity of the methanol extract was superior to that of all samples tested (IC50 = 0.21 +/- 0.04 mg/mL). PMID- 26538492 TI - HPLC/Fluorometric Detection of Carvedilol in Real Human Plasma Samples Using Liquid-Liquid Extraction. AB - A simple, rapid and sensitive high-performance liquid chromatography (HPLC) method has been developed to quantify carvedilol in human plasma using an isocratic system with fluorescence detection. The method included a single-step liquid-liquid extraction with diethylether and ethylacetate mixture (3 : 1, v/v). HPLC separation was carried out by reversed-phase chromatography with a mobile phase composed of 20 mM phosphate buffer (pH 7)-acetonitrile (65 : 35, v/v), pumped at a flow rate of 1.0 mL/min. Fluorescence detection was performed at 240 nm (excitation) and 330 nm (emission). The calibration curve for carvedilol was linear from 10 to 250 ng/mL. Intra- and interday precision values for carvedilol in human plasma were <4.93%, and accuracy (relative error) was better than 4.71%. The analytical recovery of carvedilol from human plasma averaged out to 91.8%. The limits of detection and quantification of carvedilol were 3.0 and 10 ng/mL, respectively. Also, the method was successfully applied to three patients with hypertension who had been given an oral tablet of 25 mg carvedilol. PMID- 26538493 TI - Quality improvement in documentation for patients with suspected facial fractures: use of a structured record keeping tool. AB - OBJECTIVE: Patients with injuries to the midface frequently sustain ophthalmic injuries and fractures to the facial bones. Despite this, basic ophthalmic examination and assessment of important clinical signs are often missing from the records of patients attending the emergency department (ED). We implemented a structured record keeping tool to improve documentation for patients presenting to the ED with midface injuries. METHODS: At our institution, a structured record keeping tool was introduced to document important clinical features of maxillofacial injuries. This assessment tool included 17 key clinical diagnostic signs and symptoms including a six-part basic ophthalmic examination. We audited 369 patients attending the ED with suspected midface bony injuries using this tool. RESULTS: A statistically significant improvement in the documentation of all six ophthalmic parameters was seen. The documentation rate of visual acuity increased by 41.1% (SE 2.8; p<0.001); diplopia by 45% (2.9; p<0.001); double vision by 51% (2.9; p<0.001); lateral subconjunctival haemorrhage with no posterior limit by 83% (2.6; p<0.001) and enopthalmous by 86% (2.4; p<0.001). Documenting whether pupils were equal and react to light increased by 14% (1.4; p<0.001). In addition, 10 out of 11 non-ophthalmic parameters showed significant improvement. The mean global record keeping score increased from 45.3% (95% CI 42.7% to 47.7%) to 99.1% (95% CI 98.2% to 100%; p<0.001). CONCLUSIONS: This work demonstrates that a structured record keeping tool is a simple and effective method of significantly improving clinical documentation for patients with facial injuries presenting to the ED. PMID- 26538494 TI - Serum levels of 25(OH)D are not associated with venous thromboembolism in the elderly population. A case-control study. AB - The prevalence of both vitamin D deficiency and venous thromboembolism (VTE) is important in the elderly. Previous studies have provided evidence for a possible association between vitamin D status and the risk of VTE. Thus, we aimed to investigate the association between vitamin D levels and VTE in the population aged 75 and over included in the EDITH case-control study. The association between vitamin D status and VTE was analysed. We also analysed the monthly and seasonal variations of VTE and vitamin D. Between May 2000 and December 2009, 340 elderly patients (mean age 81.5 years, 32% men) with unprovoked VTE and their controls were included. The univariate and multivariate analysis found no significant association between serum levels of vitamin D and the risk of unprovoked VTE. In the unadjusted analysis, a higher BMI was statistically associated with an increased risk of VTE (OR 1.09; 95% CI 1.05-1.13) whereas a better walking capacity and living at home were associated with a decreased rate of VTE: OR 0.57; 95% CI 0.36-0.90 and 0.40; 95% CI 0.25-0.66, respectively. Although not significant, more VTE events occurred during winter (p=0.09). No seasonal variations of vitamin D levels were found (p=0.11). In conclusion, in contrast with previous reports our findings suggest that vitamin D is not associated with VTE in the elderly population. PMID- 26538495 TI - Nanoscale Structuring of Surfaces by Using Atomic Layer Deposition. AB - Controlled structuring of surfaces is interesting for a wide variety of areas, including microelectronic device fabrication, optical devices, bio(sensing), (electro-, photo)catalysis, batteries, solar cells, fuel cells, and sorption. A unique feature of atomic layer deposition (ALD) is the possibility to form conformal uniform coatings on arbitrarily shaped materials with controlled atomic scale thickness. In this Minireview, we discuss the potential of ALD for the nanoscale structuring of surfaces, highlighting its versatile application to structuring both planar substrates and powder materials. Recent progress in the application of ALD to porous substrates has even made the nanoscale structuring of high-surface-area materials now feasible, thereby enabling novel applications, such as those in the fields of catalysis and alternative energy. PMID- 26538496 TI - Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer. AB - BACKGROUND: In a phase II study, we showed that temozolomide (TMZ) was tolerable and active in heavily pre-treated patients with advanced colorectal cancer (CRC) and MGMT methylation. A schedule of dose-dense TMZ may have enhanced activity due to the higher cumulative dose and induction of MGMT depletion, even in resistant tumors. METHODS: Thirty-two patients with chemorefractory MGMT-methylated CRC were treated with TMZ at a daily dose of 75 mg/m(2) for 21 consecutive days every 4 weeks, for up to six cycles or until the occurrence of progressive disease/unacceptable toxicity. The primary endpoint was treatment activity in terms of objective response rate (ORR). MGMT protein expression was tested by immunohistochemistry (IHC) on two pooled cohorts: patients from the previous study of standard-dose TMZ and those from the current investigation. RESULTS: From November 2013 to December 2014, 32 patients were treated at Fondazione IRCCS Istituto Nazionale dei Tumori. We observed only three episodes of grade 3 asthenia and no significant myelotoxicity. The ORR was 16 % (all partial responses occurring in RAS-BRAF-mutated tumors). Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.7 months, respectively. Patients with MGMT-low expression by IHC had a significantly higher ORR (p < 0.0001) and PFS (p = 0.001) compared to those with MGMT-high expression, while no difference was observed in OS. CONCLUSIONS: Our data confirm the encouraging activity of TMZ in chemorefractory CRC patients selected for MGMT silencing, even in the RAS-BRAF mutated population. The role of MGMT IHC as a biomarker for improving patient selection warrants further prospective confirmation. PMID- 26538497 TI - Adult-onset actinic prurigo: report of 19 patients from Taiwan. PMID- 26538498 TI - Physician spending and subsequent risk of malpractice claims: observational study. AB - STUDY QUESTION: Is a higher use of resources by physicians associated with a reduced risk of malpractice claims? METHODS: Using data on nearly all admissions to acute care hospitals in Florida during 2000-09 linked to malpractice history of the attending physician, this study investigated whether physicians in seven specialties with higher average hospital charges in a year were less likely to face an allegation of malpractice in the following year, adjusting for patient characteristics, comorbidities, and diagnosis. To provide clinical context, the study focused on obstetrics, where the choice of caesarean deliveries are suggested to be influenced by defensive medicine, and whether obstetricians with higher adjusted caesarean rates in a year had fewer alleged malpractice incidents the following year. STUDY ANSWER AND LIMITATIONS: The data included 24,637 physicians, 154,725 physician years, and 18,352,391 hospital admissions; 4342 malpractice claims were made against physicians (2.8% per physician year). Across specialties, greater average spending by physicians was associated with reduced risk of incurring a malpractice claim. For example, among internists, the probability of experiencing an alleged malpractice incident in the following year ranged from 1.5% (95% confidence interval 1.2% to 1.7%) in the bottom spending fifth ($19,725 (L12,800; ?17,400) per hospital admission) to 0.3% (0.2% to 0.5%) in the top fifth ($39,379 per hospital admission). In six of the specialties, a greater use of resources was associated with statistically significantly lower subsequent rates of alleged malpractice incidents. A principal limitation of this study is that information on illness severity was lacking. It is also uncertain whether higher spending is defensively motivated. WHAT THIS STUDY ADDS: Within specialty and after adjustment for patient characteristics, higher resource use by physicians is associated with fewer malpractice claims. FUNDING, COMPETING INTERESTS, DATA SHARING: This study was supported by the Office of the Director, National Institutes of Health (grant 1DP5OD017897-01 to ABJ) and National Institute of Aging (R37 AG036791 to JB). The authors have no competing interests or additional data to share. PMID- 26538499 TI - Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking. AB - The first fully conjugated bis-cyclopropenone (photo-DIBOD), a derivative of dibenzo[a,e][8]annulene, has been synthesized. 350-420 nm irradiation of this robust compound results in the efficient formation of dibenzo [a,e] cyclooctadiyne, an unstable, but useful SPAAC cross-linking reagent. Since photo DIBO doesn't react with organic azides, this method allows for the spatiotemporal control of the ligation of two azide-tagged substrates. PMID- 26538500 TI - An assessment of catalytic residue 3D ensembles for the prediction of enzyme function. AB - BACKGROUND: The central element of each enzyme is the catalytic site, which commonly catalyzes a single biochemical reaction with high specificity. It was unclear to us how often sites that catalyze the same or highly similar reactions evolved on different, i. e. non-homologous protein folds and how similar their 3D poses are. Both similarities are key criteria for assessing the usability of pose comparison for function prediction. RESULTS: We have analyzed the SCOP database on the superfamily level in order to estimate the number of non-homologous enzymes possessing the same function according to their EC number. 89% of the 873 substrate-specific functions (four digit EC number) assigned to mono-functional, single-domain enzymes were only found in one superfamily. For a reaction-specific grouping (three digit EC number), this value dropped to 35%, indicating that in approximately 65% of all enzymes the same function evolved in two or more non homologous proteins. For these isofunctional enzymes, structural similarity of the catalytic sites may help to predict function, because neither high sequence similarity nor identical folds are required for a comparison. To assess the specificity of catalytic 3D poses, we compiled the redundancy-free set ENZ_SITES, which comprises 695 sites, whose composition and function are well-defined. We compared their poses with the help of the program Superpose3D and determined classification performance. If the sites were from different superfamilies, the number of true and false positive predictions was similarly high, both for a coarse and a detailed grouping of enzyme function. Moreover, classification performance did not improve drastically, if we additionally used homologous sites to predict function. CONCLUSIONS: For a large number of enzymatic functions, dissimilar sites evolved that catalyze the same reaction and it is the individual substrate that determines the arrangement of the catalytic site and its local environment. These substrate-specific requirements turn the comparison of catalytic residues into a weak classifier for the prediction of enzyme function. PMID- 26538501 TI - Antimicrobial de-escalation of treatment for healthcare-associated pneumonia within the Veterans Healthcare Administration. AB - OBJECTIVES: The objective of this study was to measure quantitatively antimicrobial de-escalation utilizing electronic medication administration data based on the spectrum of activity for antimicrobial therapy (i.e. spectrum score) to identify variables associated with de-escalation in a nationwide healthcare system. METHODS: A retrospective cohort study of patients hospitalized for healthcare-associated pneumonia was conducted in Veterans Affairs Medical Centers (n = 119). Patients hospitalized for healthcare-associated pneumonia on acute care wards between 5 and 14 days who received antimicrobials for >= 3 days during calendar years 2008-11 were evaluated. The spectrum score method was applied at the patient level to measure de-escalation on day 4 of hospitalization. De escalation was expressed in aggregate and facility-level proportions. Logistic regression was used to assess variables associated with de-escalation. ORs with 95% CIs were reported. RESULTS: Among 9319 patients, the de-escalation proportion was 28.3% (95% CI 27.4-29.2), which varied 6-fold across facilities [median (IQR) facility-level de-escalation proportion 29.1% (95% CI 21.7-35.6)]. Variables associated with de-escalation included initial broad-spectrum therapy (OR 1.5, 95% CI 1.4-1.5 for each 10% increase in spectrum), collection of respiratory tract cultures (OR 1.1, 95% CI 1.0-1.2) and care in higher complexity facilities (OR 1.3, 95% CI 1.1-1.6). Respiratory tract cultures were collected from 35.3% (95% CI 32.7-37.7) of patients. CONCLUSIONS: De-escalation of antimicrobial therapy was limited and varied substantially across facilities. De-escalation was associated with respiratory tract culture collection and treatment in a high complexity-level facility. PMID- 26538502 TI - Resistance patterns in clinical isolates of pathogenic Actinomyces species. AB - OBJECTIVES: Actinomyces spp. are commensals that may occasionally invade deep tissue structures, causing difficult-to-treat and disfiguring lesions. Information on antimicrobial resistance patterns is limited to observations from two previous studies. Therefore, we examined antimicrobial resistance patterns in clinical isolates of Actinomyces spp. METHODS: In this retrospective assessment of antimicrobial resistance patterns, we identified 392 Actinomyces spp. at a tertiary care centre from January 2008 to December 2014. MICs of various antimicrobial agents, including ampicillin/sulbactam, meropenem, clindamycin, metronidazole and vancomycin for anaerobic actinomycetes, were obtained by Etest. For aerobic actinomycetes, imipenem, cefotaxime, amikacin, linezolid, moxifloxacin, trimethoprim/sulfamethoxazole and clarithromycin were tested. MIC results were interpreted based on guidelines published by the CLSI (formerly NCCLS). RESULTS: Actinomyces meyeri was predominantly isolated and accounted for 34% of all Actinomyces spp. identified, followed by Actinomyces turicensis with 23%. Actinomyces neuii is considered to be a rare Actinomyces sp., but accounted for 8% of isolates. Antimicrobial susceptibility testing of isolates showed that the Actinomyces spp. were almost uniformly susceptible to beta-lactam antimicrobials (with and without beta-lactamase inhibitors), carbapenems, tetracyclines and vancomycin. In contrast, Actinomyces spp. isolates were almost uniformly resistant to metronidazole. CONCLUSIONS: beta-Lactam antimicrobial agents remain the first choice, whereas metronidazole should be avoided, in the treatment of actinomycosis. Reasonable alternatives for treatment are tetracyclines and carbapenems. PMID- 26538503 TI - Population pharmacokinetics of linezolid in critically ill patients on renal replacement therapy: comparison of equal doses in continuous venovenous haemofiltration and continuous venovenous haemodiafiltration. AB - OBJECTIVES: Few data are available to guide linezolid dosing during renal replacement therapy. The objective of this study was to compare the population pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVHF, 30 mL/kg/h) and continuous venovenous haemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h). METHODS: Patients requiring linezolid 600 mg iv every 12 h and CVVHF or CVVHDF were eligible for this prospective study. Seven blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis was undertaken using Pmetrics. Monte Carlo simulations evaluated achievement of a pharmacodynamics target of an AUC from 0-24 h to MIC (AUC0-24/MIC) of 80. RESULTS: Nine CVVHDF and eight CVVHF treatments were performed in 13 patients. Regimens of CVVHDF and CVVHF were similar. A two-compartment linear model best described the data. CVVHDF was associated with a 20.5% higher mean linezolid clearance than CVVHF, without statistical significance (P = 0.39). Increasing patient weight and decreasing SOFA score were associated with increasing linezolid clearance. The mean (SD) parameter estimates were: clearance (CL), 3.8 (2.2) L/h; volume of the central compartment, 26.5 (10.3) L; intercompartmental clearance constants from central to peripheral, 8.1 (12.1) L/h; and peripheral to central compartments, 3.6 (4.0) L/h. Achievement of pharmacodynamic targets was poor for an MIC of 2 mg/L with the studied dose. CONCLUSIONS: During CVVHF and CVVHDF, there is profound pharmacokinetic variability of linezolid. Suboptimal achievement of therapeutic targets occurs at the EUCAST breakpoint MIC of 2 mg/L using 600 mg iv every 12 h. PMID- 26538504 TI - Evidence for the critical role of a secondary site rpoB mutation in the compensatory evolution and successful transmission of an MDR tuberculosis outbreak strain. AB - BACKGROUND: MDR Mycobacterium tuberculosis clinical strains that cause large outbreaks, particularly among HIV-negative patients, are likely to have undergone the most successful compensatory evolution. Hence, mutations secondary to the acquisition of drug resistance are worthy of consideration in these highly transmissible strains. Here, we assessed the role of a mutation within rpoB, rpoB V615M, secondary to the rifampicin resistance-conferring mutation rpoB S531L, which is associated with a major MDR tuberculosis outbreak strain that evolved in an HIV-negative context in northern Tunisia. METHODS: Using BCG as a model organism, we engineered strains harbouring either the rpoB S531L mutation alone or the double mutation rpoB S531L, V615M. Individual and competitive in vitro growth assays were performed in order to assess the relative fitness of each BCG mutant. RESULTS: The rpoB V615M mutation was found to be invariably associated with rpoB S531L. Structural analysis mapped rpoB V615M to the same bridge helix region as rpoB compensatory mutations previously described in Salmonella. Compared with the rpoB single-mutant BCG, the double mutant displayed improved growth characteristics and fitness rates equivalent to WT BCG. Strikingly, the rpoB double mutation conferred high-level resistance to rifampicin. CONCLUSIONS: Here, we demonstrated the fitness compensatory role of a mutation within rpoB, secondary to the rifampicin resistance mutation rpoB S531L, which is characteristic of an MDR M. tuberculosis major outbreak strain. The finding that this secondary mutation concomitantly increased the resistance level to rifampicin argues for its significant contribution to the successful transmission of the MDR-TB strain. PMID- 26538505 TI - A real-time PCR assay for direct characterization of the Neisseria gonorrhoeae GyrA 91 locus associated with ciprofloxacin susceptibility. AB - OBJECTIVES: The objective of this study was to develop a real-time PCR method for specific detection of the gonococcal GyrA amino acid 91 locus directly in clinical samples so as to predict Neisseria gonorrhoeae ciprofloxacin susceptibility. METHODS: The real-time PCR assay, GyrA91-PCR, was designed using two probes, one for detection of the WT S91 sequence and the other for detection of the S91F alteration. The performance of the assay was initially assessed using characterized N. gonorrhoeae isolates (n = 70), a panel of commensal Neisseria and Moraxella species (n = 55 isolates) and clinical samples providing negative results by a commercial N. gonorrhoeae nucleic acid amplification test (NAAT) method (n = 171). The GyrA91-PCR was then applied directly to N. gonorrhoeae NAAT positive clinical samples (n = 210) from the year 2014 for which corresponding N. gonorrhoeae isolates with susceptibility results were also available. RESULTS: The GyrA91-PCR accurately characterized the GyrA 91 locus of all 70 N. gonorrhoeae isolates (sensitivity = 100%, 95% CI = 94.9%-100%), whereas all non gonococcal isolates and N. gonorrhoeae NAAT-negative clinical samples gave negative results by the GyrA91-PCR (specificity = 100%, 95% CI = 98.4%-100%). When applied to the 210 N. gonorrhoeae NAAT-positive clinical samples, the GyrA91 PCR successfully characterized 195 samples (92.9%, 95% CI = 88.5%-95.9%). When compared with the corresponding bacterial culture results, positivity by the GyrA91-PCR WT probe correctly predicted N. gonorrhoeae susceptibility to ciprofloxacin in 161 of 162 (99.4%, 95% CI = 96.6%-99.9%) samples. CONCLUSIONS: The use of a PCR assay for detection of mutation in gyrA applied directly to clinical samples can predict ciprofloxacin susceptibility in N. gonorrhoeae. PMID- 26538506 TI - Plasma and intracellular exposure to ganciclovir in adult renal transplant recipients: is there an association with haematological toxicity? AB - OBJECTIVES: Ganciclovir is the most widely used treatment for cytomegalovirus infections. However, neutropenia is a frequent associated adverse effect leading to a decrease in the ganciclovir dose or discontinuation of the therapy, thereby favouring viral resistance. In the present study, the objectives were: (i) to describe the pharmacokinetics of blood and intracellular ganciclovir and its metabolites; and (ii) to explore the relationship between exposure to ganciclovir and/or its metabolites and evolution of the neutrophil count under treatment. METHODS: Pharmacokinetic profiles (pre-dose and 1, 2, 3 and 5 h after dosing) of ganciclovir and its metabolites were measured in 22 adult renal transplant patients and further modelled by a non-parametric approach (PMetrics((r))). The relationship between exposure indices to ganciclovir and the slope of the neutrophil count was investigated using multiple linear regression. RESULTS: A four-compartment open model was able to accurately describe ganciclovir and its intracellular forms. A significant association was found between intracellular ganciclovir triphosphate concentrations (AUC0-5) and the decrease in neutrophil count over the first 3 months of treatment (beta= -0.0019 +/- 5 * 10(-4); P < 0.01). CONCLUSIONS: In this population of renal transplant patients, the decrease in neutrophil count, used as a surrogate marker of haematological toxicity, was associated with ganciclovir triphosphate accumulation in blood cells. Further studies are needed to test this biomarker as a predictive factor for toxicity. PMID- 26538507 TI - Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project. AB - OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (<= 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18 4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33 6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae. PMID- 26538508 TI - Placental transfer of the HIV integrase inhibitor dolutegravir in an ex vivo human cotyledon perfusion model. AB - OBJECTIVES: Data on fetal exposure to antiretroviral agents during pregnancy are important to estimate their potential for prevention of mother-to-child transmission (PMTCT) and possible toxicity. For the recently developed HIV integrase inhibitor dolutegravir, clinical data on fetal disposition are not yet available. Dual perfusion of a single placental lobule (cotyledon) provides a useful ex vivo model to predict the in vivo maternal-to-fetal transfer of this drug. The aim of this study was to estimate the transfer of dolutegravir across the human term placenta, using a dual-perfusion cotyledon model. METHODS: After cannulation of the cotyledons (n = 6), a fetal circulation of 6 mL/min and maternal circulation of 12 mL/min were initiated. The perfusion medium consisted of Krebs-Henseleit buffer (pH = 7.2-7.4) supplemented with 10.1 mM glucose, 30 g/L human serum albumin and 0.5 mL/L heparin 5000IE. Dolutegravir was administered to the maternal circulation (~ 4.2 mg/L) and analysed by UPLC-MS/MS. RESULTS: After 3 h of perfusion, the mean +/- SD fetal-to-maternal (FTM) concentration ratio of dolutegravir was 0.6 +/- 0.2 and the mean +/- SD concentrations in the maternal and fetal compartments were 2.3 +/- 0.4 and 1.3 +/ 0.3 mg/L, respectively. CONCLUSIONS: Dolutegravir crosses the blood-placental barrier with a mean FTM concentration ratio of 0.6. Compared with other antiretroviral agents, placental transfer of dolutegravir is moderate to high. These data suggest that dolutegravir holds clinical potential for pre-exposure prophylaxis and consequently PMTCT, but also risk of fetal toxicity. PMID- 26538509 TI - Susceptibility testing breakpoints for Mycobacterium tuberculosis categorize isolates with resistance mutations in gyrA as susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB. AB - OBJECTIVES: Fluoroquinolones (FQs) are important in the treatment of MDR-TB and in the definition of XDR-TB. Our objective was to investigate how discrepancies in the phenotypic and genotypic methods for antimicrobial susceptibility testing could affect the interpretation of antimicrobial susceptibility test results. METHODS: We analysed MICs of ofloxacin and levofloxacin in Middlebrook 7H10 broth (7H10) as well as sequencing of the quinolone resistance-determining region of the gyrA gene and the MTBDRsl assay in 75 resistant isolates, including MDR and XDR strains of Mycobacterium tuberculosis. RESULTS: Among 75 resistant isolates, 27 had mutations associated with FQ resistance. Among isolates with resistance mutations in gyrA, 26% (seven of 27) were susceptible to levofloxacin and ofloxacin by phenotypic testing at 1 mg/L and 2 mg/L. The most common mutation was in codon 94 and these isolates had significantly increased MICs of levofloxacin (2-8 mg/L) compared with isolates with mutations in codon 90 (0.25-2 mg/L, P < 0.05). The sensitivity and specificity for the MTBDRsl assay compared with gyrA sequencing were 96% and 98%, respectively. CONCLUSION: Current critical concentrations may classify up to 26% of isolates with gyrA mutations as susceptible to FQs due to a close relationship between susceptible and resistant populations. These results should be considered while improving clinical breakpoints for M. tuberculosis and may have an impact on the definition of XDR TB. PMID- 26538510 TI - Return to the Taung cave paradigm. AB - OBJECTIVES: The Taung hominin fossil was recovered in 1924 during quarry operations in the tufa formations of the Buxton Limeworks. Reconstructions of the depositional environment of the juvenile Australopithecus skull have concentrated on the types of caves that form within the tufa. Hopley et al. (Am J Phys Anthropol 151 (2013) 316-324) proposed a new model in which the pink carbonate deposits, in which many of the Taung fossils are found, formed as open terrestrial pedogenic deposits. The objective here is to challenge that notion. MATERIALS AND METHODS: Observations of the depositional environments at Taung are based upon the University of the Witwatersrand paleontological excavations at the Buxton Limeworks from 1988 to 1993, and subsequent laboratory analysis of the fossils and sediments. RESULTS: Hopley et al. (Am J Phys Anthropol 151 (2013) 316 324) conflate numerous distinct outcroppings of the pink carbonates as a single "unit." The excavations revealed numerous fossiliferous deposits that differ greatly in taphonomic origins and formation processes, and that cannot be considered a "unit" despite the commonality of pink carbonates. There are deposits that fit the model proposed by Hopley et al. (Am J Phys Anthropol 151 (2013) 316-324), but they are not the ones that yielded the most significant fossils. DISCUSSION: Most of the fossiliferous deposits, including those most likely to have yielded the Taung hominin, are best reconstructed as being of karst origins. PMID- 26538511 TI - First-pass myocardial perfusion imaging with whole-heart coverage using L1-SPIRiT accelerated variable density spiral trajectories. AB - PURPOSE: To design and evaluate two-dimensional (2D) L1-SPIRiT accelerated spiral pulse sequences for first-pass myocardial perfusion imaging with whole heart coverage capable of measuring eight slices at 2 mm in-plane resolution at heart rates up to 125 beats per minute (BPM). METHODS: Combinations of five different spiral trajectories and four k-t sampling patterns were retrospectively simulated in 25 fully sampled datasets and reconstructed with L1-SPIRiT to determine the best combination of parameters. Two candidate sequences were prospectively evaluated in 34 human subjects to assess in vivo performance. RESULTS: A dual density broad transition spiral trajectory with either angularly uniform or golden angle in time k-t sampling pattern had the largest structural similarity and smallest root mean square error from the retrospective simulation, and the L1 SPIRiT reconstruction had well-preserved temporal dynamics. In vivo data demonstrated that both of the sampling patterns could produce high quality perfusion images with whole-heart coverage. CONCLUSION: First-pass myocardial perfusion imaging using accelerated spirals with optimized trajectory and k-t sampling pattern can produce high quality 2D perfusion images with whole-heart coverage at the heart rates up to 125 BPM. Magn Reson Med 76:1375-1387, 2016. (c) 2015 International Society for Magnetic Resonance in Medicine. PMID- 26538512 TI - The role of rotational thromboelastometry in assessment of haemostasis during pregnancy in women with factor XI deficiency. AB - INTRODUCTION: Women with factor XI (FXI) deficiency are at an increased risk of bleeding complications at delivery. Obstetric management is complicated by a lack of correlation between FXI level and bleeding risk. AIM: The aims of this study were to assess the difference in rotational thromboelastometry (ROTEM(r) ) in parturient women with FXI deficiency compared to parturient and non-parturient controls and to evaluate the usefulness of ROTEM(r) in assessing bleeding risk at delivery in women with FXI deficiency. METHODS: ROTEM(r) was performed on 60 women: 27 with FXI deficiency, 20 age-matched parturient controls and 12 non parturient controls. Pregnancy outcomes and haemostatic cover was reviewed in 57 deliveries of women with FXI deficiency. RESULTS: Women with FXI deficiency had a longer clotting time (CT) and clot formation time (CFT) (P < 0.001), reduced alpha angle (P < 0.001) but no difference in MCF (P = 0.054) compared to parturient controls. Compared to non-parturient controls, they had a longer CT (P < 0.001), but shorter CFT (P < 0.001), increased alpha angle (P < 0.001) and increased MCF (P = 0.005). ROTEM(r) was an additional helpful parameter in managing parturient women with FXI deficiency, reducing the need for factor administration. CONCLUSION: ROTEM(r) demonstrated hypercoagulable changes during pregnancy in women with FXI deficiency. However, they took longer to clot compared to parturient controls, but had increased clot consolidation and clot strength compared to non-parturient controls. ROTEM(r) is an additional test that is helpful to assess bleeding risk and provision of appropriate haemostatic cover at delivery. PMID- 26538513 TI - Monitoring the outcomes of interventions against Taenia solium: options and suggestions. AB - There is an increasing interest in reducing the incidence of human neurocysticercosis, caused by infection with the larval stage of Taenia solium. Several intervention trials are currently assessing various options for control of T. solium transmission. A critical aspect of these trials will be the evaluation of whether the interventions have been successful. However, there is no consensus about the most appropriate or valuable methods that should be used. Here, we undertake a critical assessment of the diagnostic tests which are currently available for human T. solium taeniasis and human and porcine cysticercosis, as well as their suitability for evaluation of intervention trial outcomes. Suggestions are made about which of the measures that are available for evaluation of T. solium interventions would be most suitable, and which methodologies are the most appropriate given currently available technologies. Suggestions are also made in relation to the most urgent research needs in order to address deficiencies in current diagnostic methods. PMID- 26538515 TI - Intraductal spread of prostate cancer into the seminal vesicles. AB - We read with interest the significance of the different types of seminal vesicle invasion described in the recent paper by Kristiansen et al 1 The three types of invasion of the seminal vesicle are well recognised, but there is a much rarer method of invasion, that is by intraductal cancer spreading up into the seminal vesicles via the ejaculatory ducts. This method has been reported in a single case report 2 but was not seen in the series by Kristiansen 1. This article is protected by copyright. All rights reserved. PMID- 26538514 TI - Active lifestyle in childhood and adolescence prevents obesity development in young adulthood. AB - OBJECTIVE: To test the hypothesis that individuals who are active but who decrease physical activity (PA) over time have a higher risk of becoming obese in young adulthood, when compared to individuals who are consistently active throughout childhood and adolescence. METHODS: Iowa Bone Development Study cohort members (242 males and 251 females) participated in accelerometry assessments, dual-energy X-ray absorptiometry scans, and dietary questionnaire surveys at ages 5, 8, 11, 13, 15, 17, and 19 years. Group-based trajectory analyses identified distinct trajectory patterns of moderate- to vigorous-intensity PA (MVPA), percentage of body fat, and energy intake. A multivariable logistic regression model was fit to estimate the odds of "becoming obese" based on the MVPA trajectories, adjusted for mother's education, somatic maturation, and energy intake. RESULTS: Among males, 74.7% had a "normal" body fat pattern, 14.6% had a "becoming obese" pattern, and 10.7% had a "consistently obese" pattern, while among females, the percentages were 58.6%, 28.6%, and 12.8%, respectively. Participants who were active (>=45 min MVPA) as children but decreased MVPA with age were more likely to become obese, compared to consistently active participants (adjusted OR = 2.77; 95% CI = 1.16, 6.58). CONCLUSIONS: An active lifestyle throughout childhood and adolescence could prevent obesity development in young adulthood. PMID- 26538517 TI - Effect and mechanism of pyridoxamine on the lipid peroxidation and stability of polyunsaturated fatty acids in beef patties. AB - BACKGROUND: Little is known about how vitamins can affect the peroxidation and stability of polyunsaturated fatty acids in cooked foods. Thus the effects of 15 vitamins on toxic malondialdehyde (MDA) formation in cooked beef patties were examined with the application of solid phase extraction and thiobarbituric acid (TBA) analysis by HPLC-DAD. The polyunsaturated fatty acid profiles in cooked beef patties treated with some vitamins were further compared with that of control sample (no vitamin addition) by GC-MS analysis. RESULTS: Pyridoxamine, pyridoxine, retinoic acid, alpha-tocopherol and L-ascorbic acid exhibited significant effects lowering the amount of MDA. It was further discovered that retinoic acid, alpha-tocopherol and l-ascorbic acid could help preserve polyunsaturated fatty acids, while pyridoxamine addition actually showed no effect upon the retention of most of the tested polyunsaturated fatty acids, even lowering the content of arachidonic acid. Further LC-MS analysis demonstrated that pyridoxamine could directly react with MDA via an addition reaction. The reaction involves a nucleophilic attack of pyridoxamine's free amine group on one of the aldehyde functional groups of MDA to form a new adduct, and may accelerate lipid peroxidation with the loss of more polyunsaturated fatty acids. CONCLUSION: Some vitamins may directly participate in lipid peroxidation and affect food quality. (c) 2015 Society of Chemical Industry. PMID- 26538518 TI - NaOH-embedded three-dimensional porous boron nitride for efficient formaldehyde removal. AB - Volatile organic compounds, especially formaldehyde (HCHO), are considered to be great sources of contaminants in indoor air. However, design and preparation of safe, cost-affordable, and reusable materials for HCHO removal at ambient conditions are still remarkably challenging. Here, we have developed a kind of novel NaOH-embedded three-dimensional porous boron nitride (NaOH-3D BN) with high and hierarchical porosities, which exhibit excellent removal performance for HCHO. The as-prepared 3D BN is used as an adsorbent and catalytic support, while the embedded NaOH is applied as a catalyst, giving rise to catalytic transformation from high-toxic HCHO to less-toxic formate and methoxy salts at room temperature. Furthermore, their effective reusability has been confirmed. Given the high removal and reusability performance as well as no use of precious materials, the NaOH-3D BN is envisaged to be valuable practically for indoor air purification. PMID- 26538516 TI - Characterisation of Shigella Spa33 and Thermotoga FliM/N reveals a new model for C-ring assembly in T3SS. AB - Flagellar type III secretion systems (T3SS) contain an essential cytoplasmic-ring (C-ring) largely composed of two proteins FliM and FliN, whereas an analogous substructure for the closely related non-flagellar (NF) T3SS has not been observed in situ. We show that the spa33 gene encoding the putative NF-T3SS C ring component in Shigella flexneri is alternatively translated to produce both full-length (Spa33-FL) and a short variant (Spa33-C), with both required for secretion. They associate in a 1:2 complex (Spa33-FL/C2) that further oligomerises into elongated arrays in vitro. The structure of Spa33-C2 and identification of an unexpected intramolecular pseudodimer in Spa33-FL reveal a molecular model for their higher order assembly within NF-T3SS. Spa33-FL and Spa33-C are identified as functional counterparts of a FliM-FliN fusion and free FliN respectively. Furthermore, we show that Thermotoga maritima FliM and FliN form a 1:3 complex structurally equivalent to Spa33-FL/C2 , allowing us to propose a unified model for C-ring assembly by NF-T3SS and flagellar-T3SS. PMID- 26538519 TI - How Epigallocatechin-3-gallate and Tetracycline Interact with the Josephin Domain of Ataxin-3 and Alter Its Aggregation Mode. AB - Epigallocatechin-3-gallate (EGCG) and tetracycline are two known inhibitors of amyloid aggregation able to counteract the fibrillation of most of the proteins involved in neurodegenerative diseases. We have recently investigated their effect on ataxin-3 (AT3), the polyglutamine-containing protein responsible for spinocerebellar ataxia type 3. We previously showed that EGCG and tetracycline can contrast the aggregation process and toxicity of expanded AT3, although by different mechanisms. Here, we have performed further experiments by using the sole Josephin domain (JD) to further elucidate the mechanism of action of the two compounds. By protein solubility assays and FTIR spectroscopy we have first observed that EGCG and tetracycline affect the JD aggregation essentially in the same way displayed when acting on the full-length expanded AT3. Then, by saturation transfer difference (STD) NMR experiments, we have shown that EGCG binds both the monomeric and the oligomeric JD form, whereas tetracycline can only interact with the oligomeric one. Surface plasmon resonance (SPR) analysis has confirmed the capability of the sole EGCG to bind monomeric JD, although with a KD value suggestive for a non-specific interaction. Our investigations provide new details on the JD interaction with EGCG and tetracycline, which could explain the different mechanisms by which the two compounds reduce the toxicity of AT3. PMID- 26538520 TI - The zebrafish as a gerontology model in nervous system aging, disease, and repair. AB - Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age associated human pathologies through a survey of the functional deficits that arise as zebrafish age. PMID- 26538521 TI - Benefits of adjunctive moxifloxacin in generalized aggressive periodontitis: a subgroup analyses in Aggregatibacter actinomycetemcomitans-positive/negative patients from a clinical trial. AB - AIM: The aim of the present study was to evaluate the influence of the baseline detection of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) on the clinical outcomes of moxifloxacin (MOX) as an adjunct to full-mouth scaling and root planing (SRP) in generalized aggressive periodontitis (GAgP). METHODS: Forty patients were randomly distributed to two therapy protocols: SRP + placebo or SRP combined with MOX. A. actinomycetemcomitans was detected using culture methods. The significance of the treatment option (MOX or SRP + placebo) on the dependent variables (probing depth [PD] and clinical attachment level [CAL]), considering the interaction with the baseline detection of A. actinomycetemcomitans, was estimated. RESULTS: MOX therapy led to a higher significant PD reduction and CAL gain in A. actinomycetemcomitans-positive patients at baseline. In A. actinomycetemcomitans-positive patients, the reduction of sites >=5 mm was higher in the MOX group. A. actinomycetemcomitans was not present in sites with PD >=6 mm in the MOX group. The interactions of A. actinomycetemcomitans and MOX were significantly associated with CAL gain and PD reduction at 6 months. CONCLUSIONS: Adjunctive MOX trended toward better clinical responses in A. actinomycetemcomitans-positive patients at baseline. These results suggest that A. actinomycetemcomitans at baseline might modify the effect of adjunctive MOX in GAgP. PMID- 26538522 TI - The obesity epidemic: time for the Government 'heavies' to step in? PMID- 26538523 TI - Comparison of health risk behavior, awareness, and health benefit beliefs of health science and non-health science students: An international study. AB - This study determines the differences in health risk behavior, knowledge, and health benefit beliefs between health science and non-health science university students in 17 low and middle income countries. Anonymous questionnaire data were collected in a cross-sectional survey of 13,042 undergraduate university students (4,981 health science and 8,061 non-health science students) from 17 universities in 17 countries across Asia, Africa, and the Americas. Results indicate that overall, health science students had the same mean number of health risk behaviors as non-health science university students. Regarding addictive risk behavior, fewer health science students used tobacco, were binge drinkers, or gambled once a week or more. Health science students also had a greater awareness of health behavior risks (5.5) than non-health science students (4.6). Linear regression analysis found a strong association with poor or weak health benefit beliefs and the health risk behavior index. There was no association between risk awareness and health risk behavior among health science students and an inverse association among non-health science students. PMID- 26538524 TI - Tenofovir alafenamide for HIV: time to switch? PMID- 26538526 TI - Long noncoding RNAs in T lymphocytes. AB - Long noncoding RNAs are recently discovered regulatory RNA molecules that do not code for proteins but influence a vast array of biologic processes. In vertebrates, the number of long noncoding RNA genes is thought to greatly exceed the number of protein-coding genes. It is also thought that long noncoding RNAs drive the biologic complexity observed in vertebrates compared with that in invertebrates. Evidence of this complexity has been found in the T-lymphocyte compartment of the adaptive immune system. In the present review, we describe our current level of understanding of the expression of specific long or large intergenic or intervening long noncoding RNAs during T-lymphocyte development in the thymus and differentiation in the periphery and highlight the mechanisms of action that specific long noncoding RNAs employ to regulate T-lymphocyte function, both in vitro and in vivo. PMID- 26538525 TI - Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non inferiority study. AB - BACKGROUND: Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. METHODS: In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov, number NCT01815736. FINDINGS: Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4.1%, 95% CI 1.6-6.7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients [21%] vs 76 [16%]). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group. INTERPRETATION: Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes. FUNDING: Gilead Sciences. PMID- 26538527 TI - Serum amyloid A inhibits osteoclast differentiation to maintain macrophage function. AB - Serum amyloid A is an acute phase protein that is elevated under inflammatory conditions. Additionally, the serum levels of serum amyloid A are associated with the progression of inflammatory arthritis; thus, serum amyloid A might be involved in the regulation of osteoclast differentiation. In the present study, we examined the effects of serum amyloid A on osteoclast differentiation and function. When bone marrow-derived macrophages, as osteoclast precursors, were stimulated with serum amyloid A in the presence of M-CSF and receptor activator of nuclear factor-kappaB ligand, osteoclast differentiation and its bone resorption activity were substantially inhibited. TLR2 was important in the inhibitory effect of serum amyloid A on osteoclast differentiation, because serum amyloid A stimulated TLR2. The inhibitory effect was absent in bone marrow derived macrophages obtained from TLR2-deficient mice. Furthermore, serum amyloid A inhibited the expression of c-Fos and nuclear factor of activated T cells c1, which are crucial transcription factors for osteoclast differentiation, but prevented downregulation of IFN regulatory factor-8, a negative regulator of osteoclast differentiation. In contrast, serum amyloid A sustained the endocytic capacity of bone marrow-derived macrophages and their ability to induce the proinflammatory cytokines, IL-6, IL-1beta, and TNF-alpha. Taken together, these results suggest that serum amyloid A, when increased by inflammatory conditions, inhibits differentiation of macrophages to osteoclasts, likely to maintain macrophage function for host defense. PMID- 26538528 TI - Inflammation and preterm birth. AB - Preterm birth is the leading cause of neonatal morbidity and mortality. Although the underlying causes of pregnancy-associated complication are numerous, it is well established that infection and inflammation represent a highly significant risk factor in preterm birth. However, despite the clinical and public health significance, infectious agents, molecular trigger(s), and immune pathways underlying the pathogenesis of preterm birth remain underdefined and represent a major gap in knowledge. Here, we provide an overview of recent clinical and animal model data focused on the interplay between infection-driven inflammation and induction of preterm birth. Furthermore, here, we highlight the critical gaps in knowledge that warrant future investigations into the interplay between immune responses and induction of preterm birth. PMID- 26538531 TI - Tumor progression, metastasis, and modulators of epithelial-mesenchymal transition in endometrioid endometrial carcinoma: an update. AB - Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis - the most fatal consequence of endometrial carcinogenesis. PMID- 26538529 TI - Role of G-CSF in monophosphoryl lipid A-mediated augmentation of neutrophil functions after burn injury. AB - Infection is the leading cause of death in severely burned patients that survive the acute phase of injury. Neutrophils are the first line of defense against infections, but hospitalized burn patients frequently cannot mount an appropriate innate response to infection. Thus, immune therapeutic approaches aimed at improving neutrophil functions after burn injury may be beneficial. Prophylactic treatment with the TLR4 agonist monophosphoryl lipid A is known to augment resistance to infection by enhancing neutrophil recruitment and facilitating bacterial clearance. This study aimed to define mechanisms by which monophosphoryl lipid A treatment improves bacterial clearance and survival in a model of burn-wound sepsis. Burn-injured mice were treated with monophosphoryl lipid A or vehicle, and neutrophil mobilization was evaluated in the presence or absence of Pseudomonas aeruginosa infection. Monophosphoryl lipid A treatment induced significant mobilization of neutrophils from the bone marrow into the blood and sites of infection. Neutrophil mobilization was associated with decreased bone marrow neutrophil CXCR4 expression and increased plasma G-CSF concentrations. Neutralization of G-CSF before monophosphoryl lipid A administration blocked monophosphoryl lipid A-induced expansion of bone marrow myeloid progenitors and mobilization of neutrophils into the blood and their recruitment to the site of infection. G-CSF neutralization ablated the enhanced bacterial clearance and survival benefit endowed by monophosphoryl lipid A in burn-wound-infected mice. Our findings provide convincing evidence that monophosphoryl lipid A-induced G-CSF facilitates early expansion, mobilization, and recruitment of neutrophils to the site of infection after burn injury, allowing for a robust immune response to infection. PMID- 26538532 TI - Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015. AB - We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures. PMID- 26538533 TI - Barriers to guideline-compliant psoriasis care: analyses and concepts. AB - Despite the availability of effective therapeutics and evidence-based treatment guidelines, a substantial proportion of patients with moderate-to-severe psoriasis does not receive appropriate care. This under-provision of health care may cause further worsening of health, remarkable limitations of the patient's quality of life, and indirect costs for the health care system. In order to provide guideline-compliant care for every psoriasis patient, it is important to identify barriers obstructing optimal care. Studies have identified various barriers on the physician's and on the patient's side; however, respective studies approached only single barriers, and not all of them in the context of psoriasis. Other publications that describe barriers systematically did not focus on psoriasis either. The objective of this literature review was to identify barriers and facilitators, based on studies analysing quality of care and single barriers, resulting in a comprehensive model of causal factors. Our analyses revealed three categories of barriers - patient-related, physician-related and external factors: On the patient side, we found non-adherence to therapies to be an important barrier, often in close association with psychiatric factors. Barriers on the physician's side predominantly are incomplete knowledge of the guidelines as well as the complexity of psoriasis comorbidity. In some countries, payment for patients with complex disease status is poor and inconsistent reimbursement regulations potentially interfere with optimal care. The current analysis indicates that most barriers are interdependent. Thus, measures approaching related barriers simultaneously are required. To improve care for psoriasis patients, further studies systematically addressing all potentially relevant barriers in conjoint are needed. PMID- 26538534 TI - Setting the record straight for fossil flying fishes versus non-flying ones: a comment on Xu et al. (2015). PMID- 26538535 TI - Telomere dynamics may link stress exposure and ageing across generations. AB - Although exposure to stressors is known to increase disease susceptibility and accelerate ageing, evidence is accumulating that these effects can span more than one generation. Stressors experienced by parents have been reported to negatively influence the longevity of their offspring and even grand offspring. The mechanisms underlying these long-term, cross-generational effects are still poorly understood, but we argue here that telomere dynamics are likely to play an important role. In this review, we begin by surveying the current connections between stress and telomere dynamics. We then lay out the evidence that exposure to stressors in the parental generation influences telomere dynamics in offspring and potentially subsequent generations. We focus on evidence in mammalian and avian studies and highlight several promising areas where our understanding is incomplete and future investigations are critically needed. Understanding the mechanisms that link stress exposure across generations requires interdisciplinary studies and is essential to both the biomedical community seeking to understand how early adversity impacts health span and evolutionary ecologists interested in how changing environmental conditions are likely to influence age-structured population dynamics. PMID- 26538536 TI - From Potanichthys to Wushaichthys: resolving the evolutionary origin and reproductive strategy of the Thoracopteridae: a reply to Tintori (2015). PMID- 26538537 TI - Spectral information as an orientation cue in dung beetles. AB - During the day, a non-uniform distribution of long and short wavelength light generates a colour gradient across the sky. This gradient could be used as a compass cue, particularly by animals such as dung beetles that rely primarily on celestial cues for orientation. Here, we tested if dung beetles can use spectral cues for orientation by presenting them with monochromatic (green and UV) light spots in an indoor arena. Beetles kept their original bearing when presented with a single light cue, green or UV, or when presented with both light cues set 180 degrees apart. When either the UV or the green light was turned off after the beetles had set their bearing in the presence of both cues, they were still able to maintain their original bearing to the remaining light. However, if the beetles were presented with two identical green light spots set 180 degrees apart, their ability to maintain their original bearing was impaired. In summary, our data show that ball-rolling beetles could potentially use the celestial chromatic gradient as a reference for orientation. PMID- 26538538 TI - Brain regions associated with visual cues are important for bird migration. AB - Long-distance migratory birds have relatively smaller brains than short-distance migrants or residents. Here, we test whether reduction in brain size with migration distance can be generalized across the different brain regions suggested to play key roles in orientation during migration. Based on 152 bird species, belonging to 61 avian families from six continents, we show that the sizes of both the telencephalon and the whole brain decrease, and the relative size of the optic lobe increases, while cerebellum size does not change with increasing migration distance. Body mass, whole brain size, optic lobe size and wing aspect ratio together account for a remarkable 46% of interspecific variation in average migration distance across bird species. These results indicate that visual acuity might be a primary neural adaptation to the ecological challenge of migration. PMID- 26538539 TI - Hygienic tendencies correlate with low geohelminth infection in free-ranging macaques. AB - Parasites are ubiquitous in nature and can be costly to animal fitness, so hosts have evolved behavioural counter-strategies to mitigate infection risk. We investigated feeding-related infection-avoidance strategies in Japanese macaques via field-experimentation and observation. We first examined risk sensitivity during foraging tasks involving faecally contaminated or debris-covered food items, and then investigated individual tendencies to manipulate food items during natural foraging bouts. We concurrently monitored geohelminth infection in all subjects. We ran a principal component analysis on the observational/experimental data to generate a hygienic index across individuals and found that hygienic tendencies towards faeces avoidance and food manipulation correlated negatively with geohelminth infection. Females scored higher in hygienic tendencies than males, which might contribute to the common vertebrate pattern of male-biased infection. The behavioural tendencies observed may reflect a general form of hygiene, providing a mechanism of behavioural immunity against parasites with implications for the evolution and diversification of health maintenance strategies in humans. PMID- 26538540 TI - Detectability matters: conspicuous nestling mouth colours make prey transfer easier for parents in a cavity nesting bird. AB - An often underappreciated function of signals is to notify receivers of the presence and position of senders. The colours that ornament the mouthparts of nestling birds, for example, have been hypothesized to evolve via selective pressure generated by parents' inability to efficiently detect and feed nestlings without such visually conspicuous targets. This proposed mechanism has primarily been evaluated with comparative studies and experimental tests for parental allocation bias, leaving untested the central assumption of this detectability hypothesis, that provisioning offspring is a visually challenging task for avian parents and conspicuous mouths help. To test this assumption, I manipulated the mouths of nestling house sparrows to appear minimally and maximally conspicuous, and quantified prey transfer difficulty as the total duration of a feeding event and the number of transfer attempts required. Prey transfer to inconspicuous nestlings was, as predicted, more difficult. While this suggests that detectability constraints could shape nestling mouth colour evolution, even minimally conspicuous nestlings were not prohibitively difficult for parents to feed, indicating that a more nuanced explanation for interspecific diversity in this trait is needed. PMID- 26538541 TI - Pace of life, predators and parasites: predator-induced life-history evolution in Trinidadian guppies predicts decrease in parasite tolerance. AB - A common evolutionary response to predation pressure is increased investment in reproduction, ultimately resulting in a fast life history. Theory and comparative studies suggest that short-lived organisms invest less in defence against parasites than those that are longer lived (the pace of life hypothesis). Combining these tenets of evolutionary theory leads to the specific, untested prediction that within species, populations experiencing higher predation pressure invest less in defence against parasites. The Trinidadian guppy, Poecilia reticulata, presents an excellent opportunity to test this prediction: guppy populations in lower courses of rivers experience higher predation pressure, and as a consequence have evolved faster life histories, than those in upper courses. Data from a large-scale field survey showed that fish infected with Gyrodactylus parasites were of a lower body condition (quantified using the scaled mass index) than uninfected fish, but only in lower course populations. Although the evidence we present is correlational, it suggests that upper course guppies sustain lower fitness costs of infection, i.e. are more tolerant, than lower course guppies. The data are therefore consistent with the pace of life hypothesis of parasite defence allocation, and suggest that life-history traits mediate the indirect effect of predators on the parasites of their prey. PMID- 26538542 TI - Medication knowledge and willingness to nurse-initiate medications in an emergency department: a mixed-methods study. AB - AIMS: To assess the medication knowledge of emergency department nurses and determine the factors affecting their nurse-initiated medication practices. BACKGROUND: Nurse-initiated medications is a vital practice for all nurses in emergency departments which improves pain assessment, provides safe pain management and reduces time-to-analgesia and other meaningful treatments. DESIGN: Mixed methods. Between September 2014-January 2015, data were collected by questionnaire assessing medication knowledge and face-to-face interviews determining factors affecting practice. RESULTS: Nurse-initiated medications frequency of the Registered Nurses ranged from 0-36 times per week dependent on employed hours and emergency department area worked. Medication knowledge was consistent among nurses, but there was an overall deficit in nurses' knowledge of mechanism of action. Four major themes were identified from the 24 interviews: patient-centred care, caution and safety as principles of practice; continuing support and education; improvement of practice over time. All nurses regard the practice positively and to be extremely beneficial to patients. Although apprehensive at the start of their nurse-initiated medications practice, confidence improved with exposure and experience. Nurses sought additional information from colleagues and the available evidence-based resources. CONCLUSION: Medication knowledge is not the sole determinant of nurse-initiated medications practice. The practice is motivated by multiple factors such as patients' needs, safety and nurses' confidence. PMID- 26538543 TI - LC-MS-MS Method for Stimulants in Wastewater During Football Games. AB - A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games. PMID- 26538544 TI - Validated Method for the Quantification of Baclofen in Human Plasma Using Solid Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry. AB - A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupole liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r(2) > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthy male volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability. PMID- 26538545 TI - Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of beta-amyloid (Abeta). Disrupted Abeta kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of Abeta-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where Abeta plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease. PMID- 26538546 TI - Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans. AB - Epidemiological, genetic association, and Mendelian randomization studies have provided strong evidence that lipoprotein (a) [Lp(a)] is an independent causal risk factor for CVD, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. Lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with CVD and aortic stenosis. These data support the notion that Lp(a) should be a target of therapy for CVD event reduction and to reduce progression of aortic stenosis. However, effective therapies to specifically reduce plasma Lp(a) levels are lacking. Recent animal and human studies have shown that Lp(a) can be specifically targeted with second generation antisense oligonucleotides (ASOs) that inhibit apo(a) mRNA translation. In apo(a) transgenic mice, an apo(a) ASO reduced plasma apo(a)/Lp(a) levels and their associated oxidized phospholipid (OxPL) levels by 86 and 93%, respectively. In cynomolgus monkeys, a second generation apo(a) ASO, ISIS-APO(a)Rx, significantly reduced hepatic apo(a) mRNA expression and plasma Lp(a) levels by >80%. Finally, in a phase I study in normal volunteers, ISIS-APO(a)Rx ASO reduced Lp(a) levels and their associated OxPL levels up to 89 and 93%, respectively, with minimal effects on other lipoproteins. ISIS-APO(a)Rx represents the first specific and potent drug in clinical development to lower Lp(a) levels and may be beneficial in reducing CVD events and progression of calcific aortic valve stenosis. PMID- 26538547 TI - Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-beta and WNT7B in Human Lung Fibroblasts. AB - The wingless (Wnt) family of signaling ligands contributes significantly to lung development and is highly expressed in patients with usual interstitial pneumonia (UIP). We sought to define the cellular distribution of Wnt5A in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and the signaling ligands that control its expression in human lung fibroblasts and IPF myofibroblasts. Tissue sections from 40 patients diagnosed with IPF or UIP were probed for the immunolocalization of Wnt5A. Further, isolated lung fibroblasts from normal or IPF human lungs, adenovirally transduced for the overexpression or silencing of Wnt7B or treated with TGF-beta1 or its inhibitor, were analyzed for Wnt5A protein expression. Wnt5A was expressed in IPF lungs by airway and alveolar epithelium, smooth muscle cells, endothelium, and myofibroblasts of fibroblastic foci and throughout the interstitium. Forced overexpression of Wnt7B with or without TGF beta1 treatment significantly increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in IPF myofibroblasts where Wnt5A was already highly expressed. The results demonstrate a wide distribution of Wnt5A expression in cells of the IPF lung and reveal that it is significantly increased by Wnt7B and TGF-beta1, which, in combination, could represent key signaling pathways that modulate the pathogenesis of IPF. PMID- 26538549 TI - Access to care in the Baltic States: did crisis have an impact? AB - BACKGROUND: In 2009, brief but deep economic crisis profoundly affected the three Baltic States: Estonia, Latvia and Lithuania. In response, all three countries adopted severe austerity measures with the shared goal of containing rising deficits, but employing different methods. AIMS: In this article, we analyze the impact of the economic crisis and post-crisis austerity measures on health systems and access to medical services in the three countries. METHODS: We use the EU-SILC data to analyze trends in unmet medical need in 2005-2012, and apply log-binomial regression to calculate the risk of unmet medical need in the pre- and post- crisis period. RESULTS: Between 2009 and 2012 unmet need has increased significantly in Latvia (OR: 1.24, 95% confidence interval (CI): 1.15-1.34) and Estonia (OR: 1.98, 95% CI: 1.72-2.27), but not Lithuania (OR: 0.84. 95% CI: 0.69 1.04). The main drivers of increased unmet need were inability to afford care in Latvia and long waiting lists in Estonia. CONCLUSION: The impact of the crisis on access to care in the three countries varied, as did the austerity measures affecting their health systems. Estonia and Latvia experienced worsening access to care, largely exacerbating already existing barriers. The example of Lithuania suggests that deterioration in access is not inevitable, once health policies prioritise maintenance and availability of existing services, or if there is room for reducing existing inefficiencies. Moreover, better financial preparedness of health systems in Estonia and Lithuania achieved some protection of the population from increasing unmet need due to the rising cost of medical care. PMID- 26538548 TI - Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy. AB - Digital image analysis of histology sections provides reliable, high-throughput methods for neuropathological studies but data is scant in frontotemporal lobar degeneration (FTLD), which has an added challenge of study due to morphologically diverse pathologies. Here, we describe a novel method of semi-automated digital image analysis in FTLD subtypes including: Pick's disease (PiD, n=11) with tau positive intracellular inclusions and neuropil threads, and TDP-43 pathology type C (FTLD-TDPC, n=10), defined by TDP-43-positive aggregates predominantly in large dystrophic neurites. To do this, we examined three FTLD-associated cortical regions: mid-frontal gyrus (MFG), superior temporal gyrus (STG) and anterior cingulate gyrus (ACG) by immunohistochemistry. We used a color deconvolution process to isolate signal from the chromogen and applied both object detection and intensity thresholding algorithms to quantify pathological burden. We found object-detection algorithms had good agreement with gold-standard manual quantification of tau- and TDP-43-positive inclusions. Our sampling method was reliable across three separate investigators and we obtained similar results in a pilot analysis using open-source software. Regional comparisons using these algorithms finds differences in regional anatomic disease burden between PiD and FTLD-TDP not detected using traditional ordinal scale data, suggesting digital image analysis is a powerful tool for clinicopathological studies in morphologically diverse FTLD syndromes. PMID- 26538550 TI - Do different parenting patterns impact the health and physical growth of 'left behind' preschool-aged children? A cross-sectional study in rural China. AB - BACKGROUND: Many migrants from rural China seek work in urban areas and leave their children in their home villages to be raised by relatives. These children are often referred to as 'left-behind children'. Parental migration tends to have a profound impact on a child's growth. This study sought to assess the prevalence of illness and malnutrition among children in rural areas raised with different parenting patterns and to explore factors affecting their health and development. METHOD: A cross-sectional survey was conducted to examine the physical health of children raised with different parenting patterns and to explore associated risk factors. In total, this study examined 735 children ages 3-6 years in eight rural villages in two counties of Shandong Province. Their primary caregivers were interviewed with a semi-structured questionnaire. Anthropometric measurements of the children were taken and their nutritional status was determined according to WHO Child Growth Standards. RESULTS: This study found a relatively high prevalence of wasting, overweight and obesity among left-behind children. After potential confounders were controlled for, the parenting pattern, annual household income and health literacy of the primary caregiver significantly influenced the health and developmental indicators of children. CONCLUSIONS: This study highlighted the impact of the characteristics of the primary caregiver on a child's health and development and the importance of practical interventions for preschool-aged children who are left behind and raised with different parenting patterns. PMID- 26538551 TI - Multiplex PCR testing for nine different sexually transmitted infections. AB - Current sexually transmitted infection (STI) testing is not optimal due to delays in reporting or missed diagnoses due to a lack of comprehensive testing. The FilmArray(r) (BioFire Diagnostics, LLC, Salt Lake City, Utah) is a user-friendly, fully automated, multiplex PCR system that is being developed for rapid point-of care use. A research-use-only STI panel including multiple PCR primer sets for each organism was designed to detect Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, Ureaplasma urealyticum, Haemophilus ducreyi, and herpes simplex virus (HSV) types 1 and 2. Standard clinical testing included Gram stain, nucleic acid amplification, wet mount examination, herpes simplex virus culture, and syphilis IgG. Standard clinical tests were not available for all the organisms tested by the FilmArray STI panel. Two hundred and ninety-five clinical specimens from 190 subjects were directly compared to standard testing. Urine (n = 146), urethral/cervical swabs (31), oral swabs (60), rectal swabs (43), and ulcer swabs (15) were tested. Among the tested samples, FilmArray detected C. trachomatis in 39 (13%), N. gonorrhoeae in 20 (7%), T. vaginalis in nine (3%), HSV 1 in five (2%), HSV 2 in five (2%), U. urealyticum in 36 (12%), M. genitalium in eight (3%), and T. pallidum in 11 (4%). Concordance between the FilmArray STI panel and standard nucleic acid amplification testing for C. trachomatis was 98% and for N. gonorrhoeae was 97%. Multiplex PCR STI testing has the potential to improve public health by providing rapid, sensitive, and reliable results within the clinic or nearby laboratory. PMID- 26538552 TI - Prevalent bacterial vaginosis infection - a risk factor for incident sexually transmitted infections in women in Durban, South Africa. AB - The association between bacterial vaginosis (BV) and incident sexually transmitted infections (STIs) in a cohort of high-risk women from Durban, South Africa was investigated in this study. We undertook a secondary analysis of the Methods for Improving Reproductive Health in Africa trial that assessed effectiveness of the latex diaphragm and lubricant gel on HIV prevention among women. During study visits, urine specimens were collected for testing for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis The presence of BV was based on vaginal pH and wet mount test assessments. The association between BV and the risk for incident STIs was determined using the Cox proportional hazards model. Prevalence of BV was 31% in a cohort of 435 women tested at baseline. Among these women, BV was significantly associated with incident Trichomonas vaginalis (14.6 per 100 PY, p = 0.03) and Chlamydia trachomatis infections (15.8 per 100 PY, p = 0.04). BV remained a significant predictor for Trichomonas vaginalis infections even after adjusting for potential confounders such as age and marital status (HR: 1.60, 95% CI: 1.00, 2.57, p = 0.04). Our study showed an association between baseline BV infections and incident Trichomonas vaginalis and Chlamydia trachomatis infections. Women with BV infections should be counselled on the use of condoms and the risk of new STIs. PMID- 26538553 TI - 2015 UK national guideline for the management of infection with Chlamydia trachomatis. AB - This guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of Chlamydia trachomatis genital infection. It covers the management of the initial presentation, as well the prevention of transmission and future infection. The guideline is aimed at individuals aged 16 years and older presenting to healthcare professionals working in departments offering Level 3 care in sexually transmitted infections management within the UK. However, the principles of the recommendations should be adopted across all levels, using local care pathways where appropriate. PMID- 26538554 TI - Anal dysplasia in HIV-infected women: a commentary on the field. AB - Anal cancer may be an emerging clinical problem in HIV-infected women particularly in resource-limited settings. Human papillomavirus (HPV) infection is a precursor to anal cancer and is prevalent in HIV-infected women, but the natural history of HPV infection and anal cancer precursors is not well described in this population. It is not known which specific dysplastic lesions in the anus are most likely to progress, and whether treatment of high grade squamous intraepithelial lesion reduces the incidence of anal cancer in women. Cervical HPV infection and associated lesions may be related to the pathogenesis and natural history of anal disease. Cervical screening is resource intensive but some limited infrastructure exists in most areas where cervical cancer is prevalent. Anal screening, however is not performed. It may be that the infrastructure for cervical screening may be leveraged in developing the appropriate research, screening and treatment tools for anal dysplasia. PMID- 26538555 TI - The phytoestrogen prunetin affects body composition and improves fitness and lifespan in male Drosophila melanogaster. AB - Dietary isoflavones, a group of secondary plant compounds that exhibit phytoestrogenic properties, are primarily found in soy. Prunetin, a representative isoflavone, was recently found to affect cell signaling in cultured cells; however, in vivo effects remain elusive. In this study, the model organism Drosophila melanogaster was used to investigate the effects of prunetin in vivo with respect to lifespan, locomotion, body composition, metabolism, and gut health. Adult flies were chronically administered a prunetin-supplemented diet. Prunetin improved median survival by 3 d, and climbing activity increased by 54% in males. In comparison with the females, male flies exhibited lower climbing activity, which was reversed by prunetin intake. Furthermore, prunetin fed males exhibited increased expression of the longevity gene Sirtuin 1 (Sir2) (22%), as well as elevated AMPK activation (51%) and triglyceride levels (29%), whereas glucose levels decreased (36%). As females are long-lived compared with their male counterparts and exhibit higher triglyceride levels, prunetin apparently "feminizes" male flies via its estrogenicity. We conclude that the lifespan-prolonging effects of prunetin in the male fruit fly depend on changes in AMPK-regulated energy homeostasis via male "feminization." Collectively, we identified prunetin as a plant bioactive compound capable of improving health status and survival in male D. melanogaster. PMID- 26538556 TI - Use of multiple modes of flight subsidy by a soaring terrestrial bird, the golden eagle Aquila chrysaetos, when on migration. AB - Large birds regularly use updrafts to subsidize flight. Although most research on soaring bird flight has focused on use of thermal updrafts, there is evidence suggesting that many species are likely to use multiple modes of subsidy. We tested the degree to which a large soaring species uses multiple modes of subsidy to provide insights into the decision-making that underlies flight behaviour. We statistically classified more than 22 000 global positioning satellite-global system for mobile communications telemetry points collected at 30-s intervals to identify the type of subsidized flight used by 32 migrating golden eagles during spring in eastern North America. Eagles used subsidized flight on 87% of their journey. They spent 41.9% +/- 1.5 ([Formula: see text], range: 18-56%) of their subsidized northbound migration using thermal soaring, 45.2% +/- 2.1 (12-65%) of time gliding between thermals, and 12.9% +/- 2.2 (1-55%) of time using orographic updrafts. Golden eagles responded to the variable local-scale meteorological events they encountered by switching flight behaviour to take advantage of multiple modes of subsidy. Orographic soaring occurred more frequently in morning and evening, earlier in the migration season, and when crosswinds and tail winds were greatest. Switching between flight modes allowed migration for relatively longer periods each day and frequent switching behaviour has implications for a better understanding of avian flight behaviour and of the evolution of use of subsidy in flight. PMID- 26538557 TI - Navigating the flow: individual and continuum models for homing in flowing environments. AB - Navigation for aquatic and airborne species often takes place in the face of complicated flows, from persistent currents to highly unpredictable storms. Hydrodynamic models are capable of simulating flow dynamics and provide the impetus for much individual-based modelling, in which particle-sized individuals are immersed into a flowing medium. These models yield insights on the impact of currents on population distributions from fish eggs to large organisms, yet their computational demands and intractability reduce their capacity to generate the broader, less parameter-specific, insights allowed by traditional continuous approaches. In this paper, we formulate an individual-based model for navigation within a flowing field and apply scaling to derive its corresponding macroscopic and continuous model. We apply it to various movement classes, from drifters that simply go with the flow to navigators that respond to environmental orienteering cues. The utility of the model is demonstrated via its application to 'homing' problems and, in particular, the navigation of the marine green turtle Chelonia mydas to Ascension Island. PMID- 26538558 TI - Shear-induced orientational dynamics and spatial heterogeneity in suspensions of motile phytoplankton. AB - Fluid flow, ubiquitous in natural and man-made environments, has the potential to profoundly impact the transport of microorganisms, including phytoplankton in aquatic habitats and bioreactors. Yet, the effect of ambient flow on the swimming behaviour of phytoplankton has remained poorly understood, largely owing to the difficulty of observing cell-flow interactions at the microscale. Here, we present microfluidic experiments where we tracked individual cells for four species of motile phytoplankton exposed to a spatially non-uniform fluid shear rate, characteristic of many flows in natural and artificial environments. We observed that medium-to-high mean shear rates (1-25 s(-1)) produce heterogeneous cell concentrations in the form of regions of accumulation and regions of depletion. The location of these regions relative to the flow depends on the cells' propulsion mechanism, body shape and flagellar arrangement, as captured by an effective aspect ratio. Species having a large effective aspect ratio accumulated in the high-shear regions, owing to shear-induced alignment of the swimming orientation with the fluid streamlines. Species having an effective aspect ratio close to unity exhibited little preferential accumulation at low-to moderate flow rates, but strongly accumulated in the low-shear regions under high flow conditions, potentially owing to an active, behavioural response of cells to shear. These observations demonstrate that ambient fluid flow can strongly affect the motility and spatial distribution of phytoplankton and highlight the rich dynamics emerging from the interaction between motility, morphology and flow. PMID- 26538559 TI - A rhythm landscape approach to the developmental dynamics of birdsong. AB - Unlike simple biological rhythms, the rhythm of the oscine bird song is a learned time series of diverse sounds that change dynamically during vocal ontogeny. How to quantify rhythm development is one of the most important challenges in behavioural biology. Here, we propose a simple method, called 'rhythm landscape', to visualize and quantify how rhythm structure, which is measured as durational patterns of sounds and silences, emerges and changes over development. Applying this method to the development of Bengalese finch songs, we show that the rhythm structure begins with a broadband rhythm that develops into diverse rhythms largely through branching from precursors. Furthermore, an information-theoretic measure, the Jensen-Shannon divergence, was used to characterize the crystallization process of birdsong rhythm, which started with a high rate of rhythm change and progressed to a stage of slow refinement. This simple method provides a useful description of rhythm development, thereby helping to reveal key temporal constraints on complex biological rhythms. PMID- 26538560 TI - Modelling stripe formation in zebrafish: an agent-based approach. AB - Zebrafish have distinctive black stripes and yellow interstripes that form owing to the interaction of different pigment cells. We present a two-population agent based model for the development and regeneration of these stripes and interstripes informed by recent experimental results. Our model describes stripe pattern formation, laser ablation and mutations. We find that fish growth shortens the necessary scale for long-range interactions and that iridophores, a third type of pigment cell, help align stripes and interstripes. PMID- 26538561 TI - Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation. AB - Regulatory T cells (Tregs) play crucial roles in maintaining immune tolerance. The transcription factor Foxp3 is a critical regulator of Treg development and function, and its expression is regulated at both transcriptional and post translational levels. Acetylation by lysine acetyl transferases/lysine deacetylases is one of the main post-translational modifications of Foxp3, which regulate Foxp3's stability and transcriptional activity. However, the mechanism(s) by which the activities of these lysine acetyl transferases/lysine deacetylases are regulated to preserve proper Foxp3 acetylation during Treg development and maintenance of Treg function remains to be determined. Here we report that Mst1 can enhance Foxp3 stability, its transcriptional activity, and Treg function by modulating the Foxp3 protein at the post-translational level. We discovered that Mst1 could increase the acetylation of Foxp3 by inhibiting Sirt1 activity, which requires the Mst1 kinase activity. We also found that Mst1 could attenuate Sirt1-mediated deacetylation of Foxp3 through directly interacting with Foxp3 to prevent or interfere the interaction between Sirt1 and Foxp3. Therefore, Mst1 can regulate Foxp3 stability in kinase-dependent and kinase-independent manners. Finally, we showed that treatment of Mst1(-/-) Tregs with Ex-527, a Sirt1-specific inhibitor, partially restored the suppressive function of Mst1(-/ ) Tregs. Our studies reveal a novel mechanism by which Mst1 enhances Foxp3 expression and Treg function at the post-translational level. PMID- 26538562 TI - Validation and Characterization of a Novel Peptide That Binds Monomeric and Aggregated beta-Amyloid and Inhibits the Formation of Neurotoxic Oligomers. AB - Although the formation of beta-amyloid (Abeta) deposits in the brain is a hallmark of Alzheimer disease (AD), the soluble oligomers rather than the mature amyloid fibrils most likely contribute to Abeta toxicity and neurodegeneration. Thus, the discovery of agents targeting soluble Abeta oligomers is highly desirable for early diagnosis prior to the manifestation of a clinical AD phenotype and also more effective therapies. We have previously reported that a novel 15-amino acid peptide (15-mer), isolated via phage display screening, targeted Abeta and attenuated its neurotoxicity (Taddei, K., Laws, S. M., Verdile, G., Munns, S., D'Costa, K., Harvey, A. R., Martins, I. J., Hill, F., Levy, E., Shaw, J. E., and Martins, R. N. (2010) Neurobiol. Aging 31, 203-214). The aim of the current study was to generate and biochemically characterize analogues of this peptide with improved stability and therapeutic potential. We demonstrated that a stable analogue of the 15-amino acid peptide (15M S.A.) retained the activity and potency of the parent peptide and demonstrated improved proteolytic resistance in vitro (stable to t = 300 min, c.f. t = 30 min for the parent peptide). This candidate reduced the formation of soluble Abeta42 oligomers, with the concurrent generation of non-toxic, insoluble aggregates measuring up to 25-30 nm diameter as determined by atomic force microscopy. The 15M S.A. candidate directly interacted with oligomeric Abeta42, as shown by coimmunoprecipitation and surface plasmon resonance/Biacore analysis, with an affinity in the low micromolar range. Furthermore, this peptide bound fibrillar Abeta42 and also stained plaques ex vivo in brain tissue from AD model mice. Given its multifaceted ability to target monomeric and aggregated Abeta42 species, this candidate holds promise for novel preclinical AD imaging and therapeutic strategies. PMID- 26538563 TI - Structural and Functional Characterization of the PaaI Thioesterase from Streptococcus pneumoniae Reveals a Dual Specificity for Phenylacetyl-CoA and Medium-chain Fatty Acyl-CoAs and a Novel CoA-induced Fit Mechanism. AB - PaaI thioesterases are members of the TE13 thioesterase family that catalyze the hydrolysis of thioester bonds between coenzyme A and phenylacetyl-CoA. In this study we characterize the PaaI thioesterase from Streptococcus pneumoniae (SpPaaI), including structural analysis based on crystal diffraction data to 1.8 A resolution, to reveal two double hotdog domains arranged in a back to back configuration. Consistent with the crystallography data, both size exclusion chromatography and small angle x-ray scattering data support a tetrameric arrangement of thioesterase domains in solution. Assessment of SpPaaI activity against a range of acyl-CoA substrates showed activity for both phenylacetyl-CoA and medium-chain fatty-acyl CoA substrates. Mutagenesis of putative active site residues reveals Asn(37), Asp(52), and Thr(68) are important for catalysis, and size exclusion chromatography analysis and x-ray crystallography confirm that these mutants retain the same tertiary and quaternary structures, establishing that the reduced activity is not a result of structural perturbations. Interestingly, the structure of SpPaaI in the presence of CoA provides a structural basis for the observed substrate specificity, accommodating a 10 carbon fatty acid chain, and a large conformational change of up to 38 A in the N terminus, and a loop region involving Tyr(38)-Tyr(39). This is the first time PaaI thioesterases have displayed a dual specificity for medium-chain acyl-CoAs substrates and phenylacetyl-CoA substrates, and we provide a structural basis for this specificity, highlighting a novel induced fit mechanism that is likely to be conserved within members of this enzyme family. PMID- 26538564 TI - BAG2 Gene-mediated Regulation of PINK1 Protein Is Critical for Mitochondrial Translocation of PARKIN and Neuronal Survival. AB - Emerging evidence has demonstrated a growing genetic component in Parkinson disease (PD). For instance, loss-of-function mutations in PINK1 or PARKIN can cause autosomal recessive PD. Recently, PINK1 and PARKIN have been implicated in the same signaling pathway to regulate mitochondrial clearance through recruitment of PARKIN by stabilization of PINK1 on the outer membrane of depolarized mitochondria. The precise mechanisms that govern this process remain enigmatic. In this study, we identify Bcl2-associated athanogene 2 (BAG2) as a factor that promotes mitophagy. BAG2 inhibits PINK1 degradation by blocking the ubiquitination pathway. Stabilization of PINK1 by BAG2 triggers PARKIN-mediated mitophagy and protects neurons against 1-methyl-4-phenylpyridinium-induced oxidative stress in an in vitro cell model of PD. Collectively, our findings support the notion that BAG2 is an upstream regulator of the PINK1/PARKIN signaling pathway. PMID- 26538565 TI - Rhodococcus erythropolis cells adapt their fatty acid composition during biofilm formation on metallic and non-metallic surfaces. AB - Several parameters are involved in bacterial adhesion and biofilm formation including surface type, medium composition and cellular surface hydrophobicty. When the cells are placed inside tubes, parameters such as oxygen availability should also influence cell adhesion. To understand which cellular lipids are involved in the molecular events of biofilm formation in Rhodococcus erythropolis, cell adhesion was promoted on different metallic and non-metallic surfaces immersed in culture media. These cells were able to modulate the fatty acid composition of the cell membrane in response to both the surface to which they adhered and the growth medium used. To assess the response of the cells to both surfaces and operational conditions, biofilms were also promoted inside a reactor built with five different types of tubes and with medium recirculation. The biofilm biomass could be directly related not to the hydrophobicity of the tubes used but to the oxygen permeability of the tubes. Besides this, cell age influenced the adhesion of the R. erythropolis cells to the tubes. Principal component analysis showed that the lipid composition of the cells could separate cells attached to metallic from those on non-metallic surfaces in the plane formed by PC1 and PC2, and influence biofilm biomass. PMID- 26538568 TI - The self-management experience of patients with type 2 diabetes and chronic kidney disease: A qualitative study. AB - BACKGROUND: The purpose of this study was to explore views related to the self management of type 2 diabetes and chronic kidney disease. METHODS: We conducted three semi-structured focus groups in participants with type 2 diabetes and chronic kidney disease. Interviews were transcribed, coded, and analyzed using thematic analysis. Credibility was supported through triangulation of data sources and the use of multiple investigators from different disciplines. RESULTS: Twenty-three adults participated. Three major themes were identified: emotional reactions to health state, the impact of family dynamics on self management, and the burden of self-management regimens. Family dynamics were found to be a barrier and support to self-management, while complicated self management regimens were found to be a barrier. Additionally, participants expressed several emotional reactions related to their CKD status, including regret related to having developed CKD and distress related both to their treatment regimens and the future possibility of dialysis. CONCLUSIONS: This exploratory study of patients with type 2 diabetes and chronic kidney disease describes barriers and supports to self-management and emotional reactions to chronic kidney disease status. Future research should confirm these findings in a larger population and should include family members and/or health care providers to help further define problems with self-management in patients with type 2 diabetes and chronic kidney disease. PMID- 26538567 TI - Evolution of lineage-specific functions in ancient cis-regulatory modules. AB - Morphological evolution is driven both by coding sequence variation and by changes in regulatory sequences. However, how cis-regulatory modules (CRMs) evolve to generate entirely novel expression domains is largely unknown. Here, we reconstruct the evolutionary history of a lens enhancer located within a CRM that not only predates the lens, a vertebrate innovation, but bilaterian animals in general. Alignments of orthologous sequences from different deuterostomes sub divide the CRM into a deeply conserved core and a more divergent flanking region. We demonstrate that all deuterostome flanking regions, including invertebrate sequences, activate gene expression in the zebrafish lens through the same ancient cluster of activator sites. However, levels of gene expression vary between species due to the presence of repressor motifs in flanking region and core. These repressor motifs are responsible for the relatively weak enhancer activity of tetrapod flanking regions. Ray-finned fish, however, have gained two additional lineage-specific activator motifs which in combination with the ancient cluster of activators and the core constitute a potent lens enhancer. The exploitation and modification of existing regulatory potential in flanking regions but not in the highly conserved core might represent a more general model for the emergence of novel regulatory functions in complex CRMs. PMID- 26538569 TI - Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis. AB - Cardiac fibrosis as a result of excessive extracellular matrix deposition leads to stiffening of the heart, which can eventually lead to heart failure. An important event in cardiac fibrosis is the transformation of fibroblasts into myofibroblasts, which secrete large amounts of extracellular matrix proteins. Although the function of protein-coding genes in myofibroblast activation and fibrosis have been a topic of investigation for a long time, it has become clear that noncoding RNAs also play key roles in cardiac fibrosis. This review discusses the involvement of microRNAs and long noncoding RNAs in cardiac fibrosis and summarizes the issues related to translating these findings into real-life therapies. PMID- 26538566 TI - Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium. AB - BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate. PMID- 26538570 TI - Evolutionary well-conserved region in the signal peptide of parathyroid hormone related protein is critical for its dual localization through the regulation of ER translocation. AB - Parathyroid hormone-related protein (PTHrP) has two different targeting signals: an N-terminal signal peptide for the endoplasmic reticulum (ER) targeting and an internal nuclear localization signal. The protein not only functions as a secretory protein, but is also found in the nucleus and/or nucleolus under certain conditions. PTHrP signal peptide is less hydrophobic than most signal peptides mainly due to its evolutionarily well-conserved region (QQWS). The substitution of four tandem leucine residues for this conserved region resulted in a significant inhibition of the signal peptide cleavage. At the same time, proportion of nuclear and/or nucleolar localization decreased, probably due to tethering of the protein to the ER membrane by the uncleaved mutant signal peptide. Almost complete cleavage of the signal peptide accompanied by a lack of nuclear/nucleolar localization was achieved by combining the hydrophobic h-region and an optimized sequence of the cleavage site. In addition, mutational modifications of the distribution of charged residues in and around the signal peptide affect its cleavage and/or nuclear/nucleolar localization of the protein. These results indicate that the well-conserved region in the signal peptide plays an essential role in the dual localization of PTHrP through ER targeting and/or the membrane translocation. PMID- 26538573 TI - Moving Liquids with Sound: The Physics of Acoustic Droplet Ejection for Robust Laboratory Automation in Life Sciences. AB - Liquid handling instruments for life science applications based on droplet formation with focused acoustic energy or acoustic droplet ejection (ADE) were introduced commercially more than a decade ago. While the idea of "moving liquids with sound" was known in the 20th century, the development of precise methods for acoustic dispensing to aliquot life science materials in the laboratory began in earnest in the 21st century with the adaptation of the controlled "drop on demand" acoustic transfer of droplets from high-density microplates for high throughput screening (HTS) applications. Robust ADE implementations for life science applications achieve excellent accuracy and precision by using acoustics first to sense the liquid characteristics relevant for its transfer, and then to actuate transfer of the liquid with customized application of sound energy to the given well and well fluid in the microplate. This article provides an overview of the physics behind ADE and its central role in both acoustical and rheological aspects of robust implementation of ADE in the life science laboratory and its broad range of ejectable materials. PMID- 26538574 TI - Axon-to-Glia Interaction Regulates GABAA Receptor Expression in Oligodendrocytes. AB - Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is available about the extent and timing of these changes or how they are regulated by oligodendrocyte-neuron interactions. Here, we used electrophysiology to study the expression of ionotropic GABA, glutamate, and ATP receptors in oligodendrocytes derived from the optic nerve and forebrain cultured either alone or in the presence of dorsal root ganglion neurons. We observed that oligodendrocytes from both regions responded to these transmitters at 1 day in culture. After the first day in culture, however, GABA sensitivity diminished drastically to less than 10%, while that of glutamate and ATP remained constant. In contrast, the GABA response amplitude was sustained and remained stable in oligodendrocytes cocultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABAA receptors and that in coculture with neurons, the oligodendrocytes bearing the receptors were those in direct contact with axons. These results reveal that GABAA receptor regulation in oligodendrocytes is driven by axonal cues and that GABA signaling may play a role in myelination and/or during axon-glia recognition. PMID- 26538575 TI - Characterization of extracellular nucleotide metabolism in Candida albicans. AB - Candida albicans is the most frequent agent of human disseminated fungal infection. Ectophosphatase and ectonucleotidase activities are known to influence the infectious potential of several microbes, including other non-albicans species of Candida. With the present work we aim to characterize these ecto enzymatic activities in C. albicans. We found that C. albicans does not have a classical ecto-5'-nucleotidase enzyme and 5'AMP is cleaved by a phosphatase instead of exclusively by a nucleotidase that also can use 3'AMP as a substrate. Moreover, these enzymatic activities are not dependent on secreted soluble enzymes and change when the yeast cells are under infection conditions, including low pH, and higher temperature and CO2 content. PMID- 26538571 TI - The role of osteoclast differentiation and function in skeletal homeostasis. AB - Osteoclasts are giant multinucleated cells that differentiate from hematopoietic cells in the bone marrow and carry out important physiological functions in the regulation of skeletal homeostasis as well as hematopoiesis. Osteoclast biology shares many features and components with cells of the immune system, including cytokine-receptor interactions (RANKL-RANK), intracellular signalling molecules (TRAF6) and transcription factors (NFATc1). Although the roles of these molecules in osteoclast differentiation are well known, fundamental questions remain unsolved, including the exact location of the RANKL-RANK interaction and the in vivo temporal and spatial information on the transformation of hematopoietic cells into bone-resorbing osteoclasts. This review focuses on the importance of cell-cell contact and metabolic adaptation for differentiation, relatively overlooked aspects of osteoclast biology and biochemistry. PMID- 26538576 TI - Spontaneous release of fluoride during the dioxygenolytic cleavage of 5 fluorosalicylate by the salicylate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans BN12. AB - The alpha-Proteobacterium Pseudaminobacter salicylatoxidans BN12 forms a peculiar gentisate 1,2-dioxygenase (SDO) that oxidatively cleaves gentisate (2,5 dihydroxybenzoate) and additionally 1-hydroxy-2-naphthoate, salicylate and various amino-, chloro-, fluoro-, hydroxy- and methylsalicylates. In the present study, the conversion of 5-fluorosalicylate by this enzyme was analysed using various analytical techniques. Spectrophotometric assays showed that the conversion of 5-fluorosalicylate by the purified enzyme resulted in the formation of a new unstable intermediate showing an absorbance maximum at lambdamax = 292 nm. The analysis of the enzymatic reaction by HPLC showed that two main products with absorbance maxima at lambdamax = 292-296 nm were formed from 5 fluorosalicylate. The same two products (although in different relative proportions) were also formed when the SDO transformed 5-chlorosalicylate or when a purified 5-nitrosalicylate 1,2-dioxygenase from Bradyrhizobium sp. JS329 oxidized 5-nitrosalicylate. A whole cell system with recombinant Escherichia coli cells overexpressing the SDO activity was established in order to produce larger amounts of the reaction products. The reaction products were subsequently identified by (1)H-NMR and mass spectrometry as stereoisomers of 2-oxo-3-(5 oxofuran-2-ylidine)propanoic acid. The release of fluoride in the course of the dioxygenolytic cleavage reaction was confirmed by ion-chromatography and (19)F NMR. PMID- 26538577 TI - Anaerobic growth of Bacillus subtilis alters the spectrum of spontaneous mutations in the rpoB gene leading to rifampicin resistance. AB - Spontaneous rifampicin-resistant (RFM(R)) mutants were isolated from Bacillus subtilis 168 cultivated in the presence or absence of oxygen. By DNA sequencing, the mutations were located within Cluster I of the rpoB gene encoding the beta subunit of RNA polymerase. The spectrum of RFM(R) rpoB mutations isolated from B. subtilis cells grown anaerobically differed from aerobically grown cells, not only with respect to the location of mutations within Cluster I but also in the class of mutation observed (transition versus transversion). In the absence of RFM, RFM(R) mutants exhibited poorer growth under anaerobic conditions than did the wild-type strain, indicating their lower fitness in the absence of antibiotic selection. PMID- 26538578 TI - Constitutive expression of the DUR1,2 gene in an industrial yeast strain to minimize ethyl carbamate production during Chinese rice wine fermentation. AB - Urea and ethanol are the main precursors of ethyl carbamate (EC) in Chinese rice wine. During fermentation, urea is generated from arginine by arginase in Saccharomyces cerevisiae, and subsequently cleaved by urea amidolyase or directly transported out of the cell into the fermentation liquor, where it reacts with ethanol to form EC. To reduce the amount of EC in Chinese rice wine, we metabolically engineered two yeast strains, N85(DUR1,2) and N85(DUR1,2)-c, from the wild-type Chinese rice wine yeast strain N85. Both new strains were capable of constitutively expressing DUR1,2 (encodes urea amidolyase) and thus enhancing urea degradation. The use of N85(DUR1,2) and N85(DUR1,2)-c reduced the concentration of EC in Chinese rice wine fermented on a small-scale by 49.1% and 55.3%, respectively, relative to fermentation with the parental strain. All of the engineered strains showed good genetic stability and minimized the production of urea during fermentation, with no exogenous genes introduced during genetic manipulation, and were therefore suitable for commercialization to increase the safety of Chinese rice wine. PMID- 26538579 TI - Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases. AB - Mitogen-activated protein kinases (MAPK) are broadly used regulators of cellular signaling. However, how these enzymes can be involved in such a broad spectrum of physiological functions is not understood. Systematic discovery of MAPK networks both experimentally and in silico has been hindered because MAPKs bind to other proteins with low affinity and mostly in less-characterized disordered regions. We used a structurally consistent model on kinase-docking motif interactions to facilitate the discovery of short functional sites in the structurally flexible and functionally under-explored part of the human proteome and applied experimental tools specifically tailored to detect low-affinity protein-protein interactions for their validation in vitro and in cell-based assays. The combined computational and experimental approach enabled the identification of many novel MAPK-docking motifs that were elusive for other large-scale protein-protein interaction screens. The analysis produced an extensive list of independently evolved linear binding motifs from a functionally diverse set of proteins. These all target, with characteristic binding specificity, an ancient protein interaction surface on evolutionarily related but physiologically clearly distinct three MAPKs (JNK, ERK, and p38). This inventory of human protein kinase binding sites was compared with that of other organisms to examine how kinase mediated partnerships evolved over time. The analysis suggests that most human MAPK-binding motifs are surprisingly new evolutionarily inventions and newly found links highlight (previously hidden) roles of MAPKs. We propose that short MAPK-binding stretches are created in disordered protein segments through a variety of ways and they represent a major resource for ancient signaling enzymes to acquire new regulatory roles. PMID- 26538581 TI - Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease: 15-Year Data From a Population-Based Longitudinal Cohort. AB - BACKGROUND: The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD. METHODS AND RESULTS: In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (P<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure. CONCLUSIONS: From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population. PMID- 26538580 TI - Study of Cardiovascular Health Outcomes in the Era of Claims Data: The Cardiovascular Health Study. AB - BACKGROUND: Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. METHODS AND RESULTS: Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI. CONCLUSIONS: The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations. PMID- 26538582 TI - Physical Activity and Risk of Coronary Heart Disease and Stroke in Older Adults: The Cardiovascular Health Study. AB - BACKGROUND: Although guidelines suggest that older adults engage in regular physical activity (PA) to reduce cardiovascular disease (CVD), surprisingly few studies have evaluated this relationship, especially in those >75 years. In addition, with advancing age the ability to perform some types of PA might decrease, making light-moderate exercise such as walking especially important to meet recommendations. METHODS AND RESULTS: Prospective cohort analysis among 4207 US men and women of a mean age of 73 years (standard deviation=6) who were free of CVD at baseline in the Cardiovascular Health Study were followed from 1989 to 1999. PA was assessed and cumulatively updated over time to minimize misclassification and assess the long-term effects of habitual activity. Walking (pace, blocks, combined walking score) was updated annually from baseline through 1999. Leisure-time activity and exercise intensity were updated at baseline, 1992, and 1996. Incident CVD (fatal or nonfatal myocardial infarction, coronary death, or stroke) was adjudicated using medical records. During 41,995 person years of follow-up, 1182 CVD events occurred. After multivariable adjustment, greater PA was inversely associated with coronary heart disease, stroke (especially ischemic stroke), and total CVD, even in those >=75 years. Walking pace, distance, and overall walking score, leisure-time activity, and exercise intensity were each associated with lower risk. For example, in comparison with a walking pace <2 mph, those that habitually walked at a pace >3 mph had a lower risk of coronary heart disease (0.50; confidence interval, 0.38-0.67), stroke (0.47; confidence interval, 033-0.66), and CVD (0.50; confidence interval, 0.40 0.62). CONCLUSIONS: These data provide empirical evidence supporting PA recommendations, in particular, walking, to reduce the incidence of CVD among older adults. PMID- 26538584 TI - Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water. AB - Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non neoplastic lesions also likely contribute to the differential tumor response. PMID- 26538585 TI - A Rare Case of Esophageal Papilloma Due to Human Papillomavirus With Uncommon Presentation of Dysphagia in a 2-Year-Old Child. PMID- 26538586 TI - Missed Opportunities for Transcranial Doppler Screening Among Children With Sickle Cell Disease. AB - Transcranial Doppler (TCD) screening rates remain low among children with sickle cell disease (SCD). We assessed TCD screening rates and missed opportunities for TCD screening. Children 2 to 16 years old with SCD enrolled in Michigan Medicaid for >=1 year (2007-2011) were identified through newborn screening. Receipt of TCD screening and presence of a missed opportunity (>=1 SCD-related outpatient visit, no TCD screening) were identified through administrative claims. Potential correlates of missed opportunities included SCD-related health services, comorbidities, and demographics. Logistic regression with generalized estimating equations modeled associations between a missed opportunity and correlates. Overall, 353 children contributed 1066 person-years. TCD screening was low yearly (10%-32%); missed opportunities occurred in 73% of the person-years. Increasing age (odds ratio [OR] = 1.11; confidence interval CI = 1.07, 1.15), previous TCD screening (OR = 0.26; CI = 0.16, 0.41), and 4 to 5 (OR = 0.48; CI = 0.26, 0.87) or >=6 outpatient visits (OR = 0.26; CI = 0.14, 0.49) were associated with a missed opportunity. Reduction of missed opportunities is a potential strategy to increase TCD screening rates. PMID- 26538583 TI - Endothelial beta-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis. AB - BACKGROUND: The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. METHODS AND RESULTS: Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial beta-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial beta-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear beta-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. CONCLUSIONS: These results demonstrate the prerequisite role of endothelial beta-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective beta catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. PMID- 26538587 TI - A Child With a Painless Lump on the Anterior Chest Wall. PMID- 26538588 TI - Low Back and Leg Pain With Refusal to Ambulate in a 6-Year-Old Male. PMID- 26538589 TI - Factors Affecting Booster Seat Use. AB - Objective To identify general awareness of booster seats as well as reasons for use and nonuse in an urban pediatric emergency room. Methods A total of 100 questionnaires were completed consisting of 24 questions each. Questions included knowledge of booster seat guidelines, source of knowledge, awareness of risks, and confidence in booster seats. Afterward, participants were provided an educational handout. Results Majority of parents reported currently using or having used a booster seat. The most popular reason was to protect from injury (78%), and reason for nonuse was size (44%). Majority of parents agreed that motor vehicle crashes were the leading cause of death in children. However, 56% of parents prematurely transitioned child out of a booster seat. Only 20% reported learning about booster seats from their pediatrician. Conclusion Parents continue to transition their children prematurely from booster seats. Current state laws need revision as well as further education using simplified illustrated guidelines. PMID- 26538590 TI - Bullying on Television: 1960-2010. AB - Bullying is a serious issue for adolescents, with health consequences both at the time of victimization and later on in adulthood. Aggression in the media is an area that has been explored as a contributing factor to bullying behavior. This study aims to determine if the incidence of aggression in popular television shows over the past 50 years has changed. A total of 198 episodes of the most popular television shows between the years 1960 and 2010 were coded for incidents of aggression and analyzed using simple linear regression. The mean number of events per episode was 8.8. No statistically significant correlation was found between number of bullying events and the years in which they occurred. Whereas it is possible that aggression on television may have an impact on bullying behaviors, there is no evidence that the incidence of bullying on television has changed significantly in the past 5 decades. PMID- 26538591 TI - Social context-dependent modification of courtship behaviour in Drosophila prolongata. AB - Induction of alternative mating tactics by surrounding conditions, such as the presence of conspecific males, is observed in many animal species. Satellite behaviour is a remarkable example in which parasitic males exploit the reproductive investment by other males. Despite the abundance of parasitic mating tactics, however, few examples are known in which males alter courtship behaviour as a counter tactic against parasitic rivals. The fruit fly Drosophila prolongata shows prominent sexual dimorphism in the forelegs. When courting females, males of D. prolongata perform 'leg vibration', in which a male vibrates the female's body with his enlarged forelegs. In this study, we found that leg vibration increased female receptivity, but it also raised a risk of interception of the female by rival males. Consequently, in the presence of rivals, males of D. prolongata shifted their courtship behaviour from leg vibration to 'rubbing', which was less vulnerable to interference by rival males. These results demonstrated that the males of D. prolongata adjust their courtship behaviour to circumvent the social context-dependent risk of leg vibration. PMID- 26538592 TI - Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa. AB - Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well documented economic impacts. However, much less is known about the population level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions. PMID- 26538593 TI - Ediacaran skeletal metazoan interpreted as a lophophorate. AB - While many skeletal biomineralized genera are described from Ediacaran (635-541 million years ago, Ma) strata, none have been suggested to have an affinity above the Porifera-Cnidaria metazoan grade. Here, we reinterpret the widespread terminal Ediacaran (approx. 550-541 Ma) sessile goblet-shaped Namacalathus as a triploblastic eumetazoan. Namacalathus has a stalked cup with radially symmetrical cross section, multiple lateral lumens and a central opening. We show that the skeleton of Namacalathus is composed of a calcareous foliated ultrastructure displaying regular concordant columnar inflections, with a possible inner organic-rich layer. These features point to an accretionary growth style of the skeleton and an affinity with the Lophotrochozoa, more specifically within the Lophophorata (Brachiopoda and Bryozoa). Additionally, we present evidence for asexual reproduction as expressed by regular budding in a bilateral pattern. The interpretation of Namacalathus as an Ediacaran total group lophophorate is consistent with an early radiation of the Lophophorata, as known early Cambrian representatives were sessile, mostly stalked forms, and in addition, the oldest known calcareous Brachiopoda (early Cambrian Obolellida) and Bryozoa (Ordovician Stenolaemata) possessed foliated ultrastructures. PMID- 26538594 TI - Milkweed butterfly resistance to plant toxins is linked to sequestration, not coping with a toxic diet. AB - Insect resistance to plant toxins is widely assumed to have evolved in response to using defended plants as a dietary resource. We tested this hypothesis in the milkweed butterflies (Danaini) which have progressively evolved higher levels of resistance to cardenolide toxins based on amino acid substitutions of their cellular sodium-potassium pump (Na(+)/K(+)-ATPase). Using chemical, physiological and caterpillar growth assays on diverse milkweeds (Asclepias spp.) and isolated cardenolides, we show that resistant Na(+)/K(+)-ATPases are not necessary to cope with dietary cardenolides. By contrast, sequestration of cardenolides in the body (as a defence against predators) is associated with the three levels of Na(+)/K(+)-ATPase resistance. To estimate the potential physiological burden of cardenolide sequestration without Na(+)/K(+)-ATPase adaptations, we applied haemolymph of sequestering species on isolated Na(+)/K(+)-ATPase of sequestering and non-sequestering species. Haemolymph cardenolides dramatically impair non adapted Na(+)/K(+)-ATPase, but had systematically reduced effects on Na(+)/K(+) ATPase of sequestering species. Our data indicate that major adaptations to plant toxins may be evolutionarily linked to sequestration, and may not necessarily be a means to eat toxic plants. Na(+)/K(+)-ATPase adaptations thus were a potential mechanism through which predators spurred the coevolutionary arms race between plants and insects. PMID- 26538595 TI - Reproductive outcome and survival of common bottlenose dolphins sampled in Barataria Bay, Louisiana, USA, following the Deepwater Horizon oil spill. AB - Common bottlenose dolphins (Tursiops truncatus) inhabit bays, sounds and estuaries across the Gulf of Mexico. Following the Deepwater Horizon oil spill, studies were initiated to assess potential effects on these ecologically important apex predators. A previous study reported disease conditions, including lung disease and impaired stress response, for 32 dolphins that were temporarily captured and given health assessments in Barataria Bay, Louisiana, USA. Ten of the sampled dolphins were determined to be pregnant, with expected due dates the following spring or summer. Here, we report findings after 47 months of follow-up monitoring of those sampled dolphins. Only 20% (95% CI: 2.50-55.6%) of the pregnant dolphins produced viable calves, as compared with a previously reported pregnancy success rate of 83% in a reference population. Fifty-seven per cent of pregnant females that did not successfully produce a calf had been previously diagnosed with moderate-severe lung disease. In addition, the estimated annual survival rate of the sampled cohort was low (86.8%, 95% CI: 80.0-92.7%) as compared with survival rates of 95.1% and 96.2% from two other previously studied bottlenose dolphin populations. Our findings confirm low reproductive success and high mortality in dolphins from a heavily oiled estuary when compared with other populations. Follow-up studies are needed to better understand the potential recovery of dolphins in Barataria Bay and, by extension, other Gulf coastal regions impacted by the spill. PMID- 26538596 TI - Evolution of early male-killing in horizontally transmitted parasites. AB - Early male-killing (MK) bacteria are vertically transmitted reproductive parasites which kill male offspring that inherit them. Whereas their incidence is well documented, characteristics allowing originally non-MK bacteria to gradually evolve MK ability remain unclear. We show that horizontal transmission is a mechanism enabling vertically transmitted bacteria to evolve fully efficient MK under a wide range of host and parasite characteristics, especially when the efficacy of vertical transmission is high. We also show that an almost 100% vertically transmitted and 100% effective male-killer may evolve from a purely horizontally transmitted non-MK ancestor, and that a 100% efficient male-killer can form a stable coexistence only with a non-MK bacterial strain. Our findings are in line with the empirical evidence on current MK bacteria, explain their high efficacy in killing infected male embryos and their variability within and across insect taxa, and suggest that they may have evolved independently in phylogenetically distinct species. PMID- 26538597 TI - Cry-wolf signals emerging from coevolutionary feedbacks in a tritrophic system. AB - For a communication system to be stable, senders should convey honest information. Providing dishonest information, however, can be advantageous to senders, which imposes a constraint on the evolution of communication systems. Beyond single populations and bitrophic systems, one may ask whether stable communication systems can evolve in multitrophic systems. Consider cross-species signalling where herbivore-induced plant volatiles (HIPVs) attract predators to reduce the damage from arthropod herbivores. Such plant signals may be honest and help predators to identify profitable prey/plant types via HIPV composition and to assess prey density via the amount of HIPVs. There could be selection for dishonest signals that attract predators for protection from possible future herbivory. Recently, we described a case in which plants release a fixed, high amount of HIPVs independent of herbivore load, adopting what we labelled a 'cry wolf' strategy. To understand when such signals evolve, we model coevolutionary interactions between plants, herbivores and predators, and show that both 'honest' and 'cry-wolf' types can emerge, depending on the assumed plant herbivore encounter rates and herbivore population density. It is suggested that the 'cry-wolf' strategy may have evolved to reduce the risk of heavy damage in the future. Our model suggests that eco-evolutionary feedback loops involving a third species may have important consequences for the stability of this outcome. PMID- 26538598 TI - Phage selection for bacterial cheats leads to population decline. AB - While predators and parasites are known for their effects on bacterial population biology, their impact on the dynamics of bacterial social evolution remains largely unclear. Siderophores are iron-chelating molecules that are key to the survival of certain bacterial species in iron-limited environments, but their production can be subject to cheating by non-producing genotypes. In a selection experiment conducted over approximately 20 bacterial generations and involving 140 populations of the pathogenic bacterium Pseudomonas aeruginosa PAO1, we assessed the impact of a lytic phage on competition between siderophore producers and non-producers. We show that the presence of lytic phages favours the non producing genotype in competition, regardless of whether iron use relies on siderophores. Interestingly, phage pressure resulted in higher siderophore production, which constitutes a cost to the producers and may explain why they were outcompeted by non-producers. By the end of the experiment, however, cheating load reduced the fitness of mixed populations relative to producer monocultures, and only monocultures of producers managed to grow in the presence of phage in situations where siderophores were necessary to access iron. These results suggest that public goods production may be modulated in the presence of natural enemies with consequences for the evolution of social strategies. PMID- 26538600 TI - Thermodynamic properties of water molecules in the presence of cosolute depend on DNA structure: a study using grid inhomogeneous solvation theory. AB - In conditions that mimic those of the living cell, where various biomolecules and other components are present, DNA strands can adopt many structures in addition to the canonical B-form duplex. Previous studies in the presence of cosolutes that induce molecular crowding showed that thermal stabilities of DNA structures are associated with the properties of the water molecules around the DNAs. To understand how cosolutes, such as ethylene glycol, affect the thermal stability of DNA structures, we investigated the thermodynamic properties of water molecules around a hairpin duplex and a G-quadruplex using grid inhomogeneous solvation theory (GIST) with or without cosolutes. Our analysis indicated that (i) cosolutes increased the free energy of water molecules around DNA by disrupting water-water interactions, (ii) ethylene glycol more effectively disrupted water-water interactions around Watson-Crick base pairs than those around G-quartets or non-paired bases, (iii) due to the negative electrostatic potential there was a thicker hydration shell around G-quartets than around Watson-Crick-paired bases. Our findings suggest that the thermal stability of the hydration shell around DNAs is one factor that affects the thermal stabilities of DNA structures under the crowding conditions. PMID- 26538601 TI - Re-evaluating the kinetics of ATP hydrolysis during initiation of DNA sliding by Type III restriction enzymes. AB - DNA cleavage by the Type III restriction enzymes requires long-range protein communication between recognition sites facilitated by thermally-driven 1D diffusion. This 'DNA sliding' is initiated by hydrolysis of multiple ATPs catalysed by a helicase-like domain. Two distinct ATPase phases were observed using short oligoduplex substrates; the rapid consumption of ~10 ATPs coupled to a protein conformation switch followed by a slower phase, the duration of which was dictated by the rate of dissociation from the recognition site. Here, we show that the second ATPase phase is both variable and only observable when DNA ends are proximal to the recognition site. On DNA with sites more distant from the ends, a single ATPase phase coupled to the conformation switch was observed and subsequent site dissociation required little or no further ATP hydrolysis. The overall DNA dissociation kinetics (encompassing site release, DNA sliding and escape via a DNA end) were not influenced by the second phase. Although the data simplifies the ATP hydrolysis scheme for Type III restriction enzymes, questions remain as to why multiple ATPs are hydrolysed to prepare for DNA sliding. PMID- 26538599 TI - Tools and data services registry: a community effort to document bioinformatics resources. AB - Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools. PMID- 26538602 TI - HSP70 binding protein 1 (HspBP1) suppresses HIV-1 replication by inhibiting NF kappaB mediated activation of viral gene expression. AB - HIV-1 efficiently hijacks host cellular machinery and exploits a plethora of host viral interactions for its successful survival. Identifying host factors that affect susceptibility or resistance to HIV-1 may offer a promising therapeutic strategy against HIV-1. Previously, we have reported that heat shock proteins, HSP40 and HSP70 reciprocally regulate HIV-1 gene-expression and replication. In the present study, we have identified HSP70 binding protein 1 (HspBP1) as a host intrinsic inhibitor of HIV-1. HspBP1 level was found to be significantly down modulated during HIV-1 infection and virus production inversely co-related with HspBP1 expression. Our results further demonstrate that HspBP1 inhibits HIV-1 long terminal repeat (LTR) promoter activity. Gel shift and chromatin immunoprecipitation assays revealed that HspBP1 was recruited on HIV-1 LTR at NF kappaB enhancer region (kappaB sites). The binding of HspBP1 to kappaB sites obliterates the binding of NF-kappaB hetero-dimer (p50/p65) to the same region, leading to repression in NF-kappaB mediated activation of LTR-driven gene expression. HspBP1 also plays an inhibitory role in the reactivation of latently infected cells, corroborating its repressive effect on NF-kappaB pathway. Thus, our results clearly show that HspBP1 acts as an endogenous negative regulator of HIV-1 gene-expression and replication by suppressing NF-kappaB-mediated activation of viral transcription. PMID- 26538603 TI - Effects of scratching and other counterstimuli on responses of trigeminothalamic tract neurons to itch-inducing stimuli in rats. AB - Counterstimuli such as scratching, pinching, noxious heat and cold, and innocuous cooling and warming have been shown to inhibit itch in humans. In the present study, the effects of each of these counterstimuli were determined on baseline firing rates and on sustained pruriceptive responses of rat trigeminothalamic tract neurons. We found that scratching had little, if any, effect on baseline firing levels but greatly reduced mean pruriceptive firing following scratching for nearly 1 min. None of the other noxious or innocuous counterstimuli significantly inhibited pruriceptive responses. Our results indicate that scratching, but not other counterstimuli, significantly reduces itch-induced responses of trigeminothalamic tract neurons. PMID- 26538604 TI - Changes in cortical activity measured with EEG during a high-intensity cycling exercise. AB - This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by ~48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes (P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution. PMID- 26538605 TI - Characterizing the physiological and behavioral roles of proctolin in Drosophila melanogaster. AB - The neuropeptide proctolin (RYLPT) plays important roles as both a neurohormone and a cotransmitter in arthropod neuromuscular systems. We used third-instar Drosophila larvae as a model system to differentiate synaptic effects of this peptide from its direct effects on muscle contractility and to determine whether proctolin can work in a cell-selective manner on muscle fibers. Proctolin did not appear to alter the amplitude of excitatory junctional potentials but did induce sustained muscle contractions in preparations where the CNS had been removed and no stimuli were applied to the remaining nerves. Proctolin-induced contractions were dose-dependent, were reduced by knocking down expression of the Drosophila proctolin receptor in muscle tissue, and were larger in some muscle cells than others (i.e., larger in fibers 4, 12, and 13 than in 6 and 7). Proctolin also increased the amplitude of nerve-evoked contractions in a dose-dependent manner, and the magnitude of this effect was also larger in some muscle cells than others (again, larger in fibers 4, 12, and 13 than in 6 and 7). Increasing the intraburst impulse frequency and number of impulses per burst increased the magnitude of proctolin's enhancement of nerve-evoked contractions and decreased the threshold and EC50 concentrations for proctolin to enhance nerve-evoked contractions. Reducing proctolin receptor expression decreased the velocity of larval crawling at higher temperatures, and thermal preference in these larvae. Our results suggest that proctolin acts directly on body-wall muscles to elicit slow, sustained contractions and to enhance nerve-evoked contractions, and that proctolin affects muscle fibers in a cell-selective manner. PMID- 26538606 TI - Voluntary reaction time and long-latency reflex modulation. AB - Stretching a muscle of the upper limb elicits short (M1) and long-latency (M2) reflexes. When the participant is instructed to actively compensate for a perturbation, M1 is usually unaffected and M2 increases in size and is followed by the voluntary response. It remains unclear if the observed increase in M2 is due to instruction-dependent gain modulation of the contributing reflex mechanism(s) or results from voluntary response superposition. The difficulty in delineating between these alternatives is due to the overlap between the voluntary response and the end of M2. The present study manipulated response accuracy and complexity to delay onset of the voluntary response and observed the corresponding influence on electromyographic activity during the M2 period. In all active conditions, M2 was larger compared with a passive condition where participants did not respond to the perturbation; moreover, these changes in M2 began early in the appearance of the response (~ 50 ms), too early to be accounted for by voluntary overlap. Voluntary response latency influenced the latter portion of M2, with the largest activity seen when accuracy of limb position was not specified. However, when participants aimed for targets of different sizes or performed movements of various complexities, reaction time differences did not influence M2 period activity, suggesting voluntary activity was sufficiently delayed. Collectively, our results show that while a perturbation applied to the upper limbs can trigger a voluntary response at short latency (<100 ms), instruction-dependent reflex gain modulation remains an important contributor to EMG changes during the M2 period. PMID- 26538608 TI - Functional morphometry demonstrates extraocular muscle compartmental contraction during vertical gaze changes. AB - Anatomical studies demonstrate selective compartmental innervation of most human extraocular muscles (EOMs), suggesting the potential for differential compartmental control. This was supported by magnetic resonance imaging (MRI) demonstrating differential lateral rectus (LR) compartmental contraction during ocular counterrolling, differential medial rectus (MR) compartmental contraction during asymmetric convergence, and differential LR, inferior rectus (IR), and superior oblique (SO) compartmental contraction during vertical vergence. To ascertain possible differential compartmental EOM contraction during vertical ductions, surface coil MRI was performed over a range of target-controlled vertical gaze positions in 25 orbits of 13 normal volunteers. Cross-sectional areas and partial volumes of EOMs were analyzed in contiguous, quasi-coronal 2-mm image planes spanning origins to globe equator to determine morphometric features correlating best with contractility. Confirming and extending prior findings for horizontal EOMs during horizontal ductions, the percent change in posterior partial volume (PPV) of vertical EOMs from 8 to 14 mm posterior to the globe correlated best with vertical duction. EOMs were then divided into equal transverse compartments to evaluate the effect of vertical gaze on changes in PPV. Differential contractile changes were detected in the two compartments of the same EOM during infraduction for the IR medial vs. lateral (+4.4%, P = 0.03), LR inferior vs. superior (+4.0%, P = 0.0002), MR superior vs. inferior (-6.0%, P = 0.001), and SO lateral vs. medial (+9.7%, P = 0.007) compartments, with no differential contractile changes in the superior rectus. These findings suggest that differential compartmental activity occurs during normal vertical ductions. Thus all EOMs may contribute to cyclovertical actions. PMID- 26538607 TI - Association between resting-state brain functional connectivity and muscle sympathetic burst incidence. AB - The insula (IC) and cingulate are key components of the central autonomic network and central nodes of the salience network (SN), a set of spatially distinct but temporally correlated brain regions identified with resting-state (task free) functional MRI (rsMRI). To examine the SN's involvement in sympathetic outflow, we tested the hypothesis that individual differences in intrinsic connectivity of the SN correlate positively with resting postganglionic muscle sympathetic nerve activity (MSNA) burst incidence (BI) in subjects without and with obstructive sleep apnea (OSA). Overnight polysomnography, 5-min rsMRI, and fibular MSNA recording were performed in 36 subjects (mean age 57 yr; 10 women, 26 men). Independent component analysis (ICA) of the entire cohort identified the SN as including bilateral IC, pregenual anterior cingulate cortex (pgACC), midcingulate cortex (MCC), and the temporoparietal junction (TPJ). There was a positive correlation between BI and the apnea-hypopnea index (AHI) (P < 0.001), but dual regression analysis identified no differences in SN functional connectivity between subjects with no or mild OSA (n = 17) and moderate or severe (n = 19) OSA. Correlation analysis relating BI to the strength of connectivity within the SN revealed large (i.e., spatial extent) and strong correlations for the left IC (P < 0.001), right pgACC/MCC (P < 0.006), left TPJ (P < 0.004), thalamus (P < 0.035), and cerebellum (P < 0.013). Indexes of sleep apnea were unrelated to BI and the strength of SN connectivity. There were no relationships between BI and default or sensorimotor network connectivity. This study links connectivity within the SN to MSNA, demonstrating several of its nodes to be key sympathoexcitatory regions. PMID- 26538609 TI - Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys. AB - Conventional anti-Parkinsonian dopamine replacement therapy is often complicated by side effects that limit the use of these medications. There is a continuing need to develop nondopaminergic approaches to treat Parkinsonism. One such approach is to use medications that normalize dopamine depletion-related firing abnormalities in the basal ganglia-thalamocortical circuitry. In this study, we assessed the potential of a specific T-type calcium channel blocker (ML218) to eliminate pathologic burst patterns of firing in the basal ganglia-receiving territory of the motor thalamus in Parkinsonian monkeys. We also carried out an anatomical study, demonstrating that the immunoreactivity for T-type calcium channels is strongly expressed in the motor thalamus in normal and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. At the electron microscopic level, dendrites accounted for >90% of all tissue elements that were immunoreactive for voltage-gated calcium channel, type 3.2-containing T-type calcium channels in normal and Parkinsonian monkeys. Subsequent in vivo electrophysiologic studies in awake MPTP-treated Parkinsonian monkeys demonstrated that intrathalamic microinjections of ML218 (0.5 MUl of a 2.5-mM solution, injected at 0.1-0.2 MUl/min) partially normalized the thalamic activity by reducing the proportion of rebound bursts and increasing the proportion of spikes in non-rebound bursts. The drug also attenuated oscillatory activity in the 3-13-Hz frequency range and increased gamma frequency oscillations. However, ML218 did not normalize Parkinsonism-related changes in firing rates and oscillatory activity in the beta frequency range. Whereas the described changes are promising, a more complete assessment of the cellular and behavioral effects of ML218 (or similar drugs) is needed for a full appraisal of their anti Parkinsonian potential. PMID- 26538611 TI - How to discriminate conclusively among different models of decision making? AB - A popular and successful class of decision-making models (the "evidence accumulator" models) has been recently challenged by a new hypothesis called the urgency-gating model. Hawkins et al. (J Neurophysiol 114: 40-47, 2015) used a sophisticated curve-fitting procedure to show that these models are discriminable and thus testable in constant evidence tasks. In this Neuro Forum article I raise possible limitations of such an approach, discuss some of its implications, and propose alternative solutions. PMID- 26538610 TI - Interhemispheric connectivity during bimanual isometric force generation. AB - Interhemispheric interactions through the corpus callosum play an important role in the control of bimanual forces. However, the extent to which physiological connections between primary motor cortices are modulated during increasing levels of bimanual force generation in intact humans remains poorly understood. Here we studied coherence between electroencephalographic (EEG) signals and the ipsilateral cortical silent period (iSP), two well-known measures of interhemispheric connectivity between motor cortices, during unilateral and bilateral 10%, 40%, and 70% of maximal isometric voluntary contraction (MVC) into index finger abduction. We found that EEG-EEG coherence in the alpha frequency band decreased while the iSP area increased during bilateral compared with unilateral 40% and 70% but not 10% of MVC. Decreases in coherence in the alpha frequency band correlated with increases in the iSP area, and subjects who showed this inverse relation were able to maintain more steady bilateral muscle contractions. To further examine the relationship between the iSP and coherence we electrically stimulated the ulnar nerve at the wrist at the alpha frequency. Electrical stimulation increased coherence in the alpha frequency band and decreased the iSP area during bilateral 70% of MVC. Altogether, our findings demonstrate an inverse relation between alpha oscillations and the iSP during strong levels of bimanual force generation. We suggest that interactions between neural pathways mediating alpha oscillatory activity and transcallosal inhibition between motor cortices might contribute to the steadiness of strong bilateral isometric muscle contractions in intact humans. PMID- 26538613 TI - Properties of an intermediate-duration inactivation process of the voltage-gated sodium conductance in rat hippocampal CA1 neurons. AB - Rapid transmembrane flow of sodium ions produces the depolarizing phase of action potentials (APs) in most excitable tissue through voltage-gated sodium channels (NaV). Macroscopic currents display rapid activation followed by fast inactivation (IF) within milliseconds. Slow inactivation (IS) has been subsequently observed in several preparations including neuronal tissues. IS serves important physiological functions, but the kinetic properties are incompletely characterized, especially the operative timescales. Here we present evidence for an "intermediate inactivation" (II) process in rat hippocampal CA1 neurons with time constants of the order of 100 ms. The half-inactivation potentials (V0.5) of steady-state inactivation curves were hyperpolarized by increasing conditioning pulse duration from 50 to 500 ms and could be described by a sum of Boltzmann relations. II state transitions were observed after opening as well as subthreshold potentials. Entry into II after opening was relatively insensitive to membrane potential, and recovery of II became more rapid at hyperpolarized potentials. Removal of fast inactivation with cytoplasmic papaine revealed time constants of INa decay corresponding to II and IS with long depolarizations. Dynamic clamp revealed attenuation of trains of APs over the 10(2)-ms timescale, suggesting a functional role of II in repetitive firing accommodation. These experimental findings could be reproduced with a five-state Markov model. It is likely that II affects important aspects of hippocampal neuron response and may provide a drug target for sodium channel modulation. PMID- 26538612 TI - Two distinct representations of social vocalizations in the basolateral amygdala. AB - Acoustic communication signals carry information related to the types of social interactions by means of their "acoustic context," the sequencing and temporal emission pattern of vocalizations. Here we describe responses to natural vocal sequences in adult big brown bats (Eptesicus fuscus). We first assessed how vocal sequences modify the internal affective state of a listener (via heart rate). The heart rate of listening bats was differentially modulated by vocal sequences, showing significantly greater elevation in response to moderately aggressive sequences than appeasement or neutral sequences. Next, we characterized single neuron responses in the basolateral amygdala (BLA) of awake, restrained bats to isolated syllables and vocal sequences. Two populations of neurons distinguished by background firing rates also differed in acoustic stimulus selectivity. Low background neurons (<1 spike/s) were highly selective, responding on average to one tested stimulus. These may participate in a sparse code of vocal stimuli, in which each neuron responds to one or a few stimuli and the population responds to the range of vocalizations across behavioral contexts. Neurons with higher background rates (>=1 spike/s) responded broadly to tested stimuli and better represented the timing of syllables within sequences. We found that spike timing information improved the ability of these neurons to discriminate among vocal sequences and among the behavioral contexts associated with sequences compared with a rate code alone. These findings demonstrate that the BLA contains multiple robust representations of vocal stimuli that can provide the basis for emotional/physiological responses to these stimuli. PMID- 26538614 TI - Educational inequality in cardiovascular disease depends on diagnosis: A nationwide register based study from Denmark. AB - BACKGROUND: Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses. DESIGN: Register based study. METHODS: Comparison of the extent of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular diagnoses: ischaemic heart disease, acute myocardial infarction, valvular heart disease, congestive heart failure, atrial fibrillation and stroke in the period 2005-2009. All individuals in the general Danish population aged 35-84 years were followed in national registers regarding hospitalisation, death and education from 1985 to 2009 (annual average of 2.9 million people) to define incident cases. RESULTS: Marked educational inequality was found in the incidence of ischaemic heart disease, acute myocardial infarction, heart failure and stroke (relative index of inequality: 0.37 (95% confidence interval 0.34; 0.40) to 0.60 (0.57; 0.63), absolute index of inequality: -241 (-254.4; -227.4) to -37 (-42.7; -31.1)) while inequality in atrial fibrillation and, in particular, in valvular heart disease was small and insignificant (relative index of inequality: 0.57 (0.49; 0.65) to 0.97 (0.88; 1.08), absolute index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; 3.8)). CONCLUSION: The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found between men and women. PMID- 26538615 TI - Clinical evolution of post-transplant diabetes mellitus. AB - BACKGROUND: The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS: We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for <=5 years. RESULTS: Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (<=3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS: PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice. PMID- 26538616 TI - PLASTIC SCINTILLATOR FOR RADIATION DOSIMETRY. AB - Inorganic scintillators, composed of high-atomic-number materials such as the CsI(Tl) scintillator, are commonly used in commercially available a silicon diode and a scintillator embedded indirect-type electronic personal dosimeters because the light yield of the inorganic scintillator is higher than that of an organic scintillator. However, when it comes to tissue-equivalent dose measurements, a plastic scintillator such as polyvinyl toluene (PVT) is a more appropriate material than an inorganic scintillator because of the mass energy absorption coefficient. To verify the difference in the absorbed doses for each scintillator, absorbed doses from the energy spectrum and the calculated absorbed dose were compared. From the results, the absorbed dose of the plastic scintillator was almost the same as that of the tissue for the overall photon energy. However, in the case of CsI, it was similar to that of the tissue only for a photon energy from 500 to 4000 keV. Thus, the values and tendency of the mass energy absorption coefficient of the PVT are much more similar to those of human tissue than those of the CsI. PMID- 26538617 TI - CHARACTERISING THE EOS SLOT-SCANNING SYSTEM WITH THE EFFECTIVE DETECTIVE QUANTUM EFFICIENCY. AB - As opposed to the standard detective quantum efficiency (DQE), effective DQE (eDQE) is a figure of merit that allows comparing the performances of imaging systems in the presence of scatter rejection devices. The geometry of the EOSTM slot-scanning system is such that the detector is self-collimated and rejects scattered radiation. In this study, the EOS system was characterised using the eDQE in imaging conditions similar to those used in clinical practice: with phantoms of different widths placed in the X-ray beam, for various incident air kerma and tube voltages corresponding to the phantom thickness. Scatter fractions in EOS images were extremely low, around 2 % for all configurations. Maximum eDQE values spanned 9-14.8 % for a large range of air kerma at the detector plane from 0.01 to 1.34 uGy. These figures were obtained with non-optimised EOS setting but still over-performed most of the maximum eDQEs recently assessed for various computed radiology and digital radiology systems with antiscatter grids. PMID- 26538618 TI - Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients. AB - BACKGROUND: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS. METHODS: We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low ADC lesions and 2 post-bevacizumab scans <=90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05. RESULTS: Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004). CONCLUSIONS: The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms. PMID- 26538620 TI - Solitaire salvage: a stent retriever-assisted catheter reduction technical report. AB - The endovascular management of giant aneurysms often proves difficult with standard techniques. Obtaining distal access to allow catheter reduction is often key to approaching these aneurysms, but several anatomic challenges make this task unsafe and not feasible. Obtaining distal anchor points and performing catheter reduction maneuvers using adjunctive devices is not a novel concept, however using the Solitaire in order to do so may have some distinct advantages compared with previously described methods. Here we describe our novel Solitaire salvage technique, which allowed successful reduction of a looped catheter within an aneurysm in three cases. While this technique is expensive and therefore best performed after standard maneuvers have failed, in our experience it was effective, safe, and more efficient than other methods. PMID- 26538619 TI - Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization. AB - BACKGROUND: Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell-derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. METHODS: To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. RESULTS: GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. CONCLUSION: CSF 1R inhibition may be a promising strategy to improve GBM response to radiotherapy. PMID- 26538621 TI - Scientists Journey Into Genomes Via CRISPR-Cas9. PMID- 26538622 TI - Targeted Therapy Makes Inroads in Medulloblastoma. PMID- 26538624 TI - Studying Pets' Cancers May Yield Health Benefits For Humans. PMID- 26538625 TI - American Society of Clinical Oncology Developing First Clinical Trial. PMID- 26538627 TI - Use of Radioactive Iodine for Thyroid Cancer and Risk of Second Primary Malignancy: A Nationwide Population-Based Study. AB - BACKGROUND: Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking. METHODS: Patients without antecedent cancer age 20 years or older and newly diagnosed with thyroid cancer were recruited from the Taiwan National Health Insurance database between 1997 and 2010. Standardized incidence ratios (SIRs) for the cancers were calculated to compare the incidence of thyroid cancer with the general population. The association between RAI dosage and cancer development was estimated using time-dependent Cox regression analysis. All statistical tests were two-sided. RESULTS: A total of 692 cases of SPM were identified among 20 235 patients with thyroid cancer. Regarding the latter, 79.7% of the patients were women, the median age was 46 years, and the follow-up period included 134 178 person-years. The SIR for any SPM was 1.41 (95% confidence interval [CI] = 1.31 to 1.52). A statistically significantly higher SIR was observed in leukemia (2.74), non-Hodgkin's lymphoma (2.38), prostate (2.30), lung and mediastinum (1.93), pancreas (1.83), kidney (1.81), breast (1.48), and colon-rectum (1.31) cancers. Cumulative RAI dose (per 30 mCi increase) conferred a strong risk for SPM (adjusted hazard ratio [aHR] = 1.01, 95% CI = 1.01 to 1.02, P < .001) and leukemia (aHR = 1.03, 95% CI = 1.02 to 1.04, P < .001) occurrences. A cumulative RAI dose greater than 150 mCi possessed a statistically significant risk for all cancer combined (aHR = 1.30) and leukemia (aHR = 6.03). CONCLUSIONS: An increased risk of SPM was observed for thyroid cancer patients, especially with cumulative RAI doses over 150 mCi. PMID- 26538628 TI - Cancer Models and Real-world Data: Better Together. AB - Decision-analytic models are increasingly used to inform health policy decisions. These models synthesize available data on disease burden and intervention effectiveness to project estimates of the long-term consequences of care, which are often absent when clinical or policy decisions must be made. While models have been influential in informing US cancer screening guidelines under ideal conditions, incorporating detailed data on real-world screening practice has been limited given the complexity of screening processes and behaviors throughout diverse health delivery systems in the United States. We describe the synergies that exist between decision-analytic models and health care utilization data that are increasingly accessible through research networks that assemble data from the growing number of electronic medical record systems. In particular, we present opportunities to enrich cancer screening models by grounding analyses in real world data with the goals of projecting the harms and benefits of current screening practices, evaluating the value of existing and new technologies, and identifying the weakest links in the cancer screening process where efforts for improvement may be most productively focused. We highlight the example of the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR), a collaboration to harmonize and analyze screening process and outcomes data on breast, colorectal, and cervical cancers across seven research centers. The pairing of models with such data can create more robust models to not only better inform policy but also inform health care systems about best approaches to improve the provision of cancer screening in the United States. PMID- 26538629 TI - Slowing Polycystic Kidney Disease by Fasting. PMID- 26538630 TI - Models of Human AKI: Resemblance, Reproducibility, and Return on Investment. PMID- 26538631 TI - Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial. AB - Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes. PMID- 26538632 TI - Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate Model. AB - Kidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim 3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models. PMID- 26538633 TI - Food Restriction Ameliorates the Development of Polycystic Kidney Disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%-40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD. PMID- 26538635 TI - The nature of alarm communication in Constrictotermes cyphergaster (Blattodea: Termitoidea: Termitidae): the integration of chemical and vibroacoustic signals. AB - Alarm signalling is of paramount importance to communication in all social insects. In termites, vibroacoustic and chemical alarm signalling are bound to operate synergistically but have never been studied simultaneously in a single species. Here, we inspected the functional significance of both communication channels in Constrictotermes cyphergaster (Termitidae: Nasutitermitinae), confirming the hypothesis that these are not exclusive, but rather complementary processes. In natural situations, the alarm predominantly attracts soldiers, which actively search for the source of a disturbance. Laboratory testing revealed that the frontal gland of soldiers produces a rich mixture of terpenoid compounds including an alarm pheromone. Extensive testing led to identification of the alarm pheromone being composed of abundant monoterpene hydrocarbons (1S) alpha-pinene and myrcene, along with a minor component, (E)-beta-ocimene. The vibratory alarm signalling consists of vibratory movements evidenced as bursts; a series of beats produced predominantly by soldiers. Exposing termite groups to various mixtures containing the alarm pheromone (crushed soldier heads, frontal gland extracts, mixture of all monoterpenes, and the alarm pheromone mixture made of standards) resulted in significantly higher activity in the tested groups and also increased intensity of the vibratory alarm communication, with the responses clearly dose-dependent. Lower doses of the pheromone provoked higher numbers of vibratory signals compared to higher doses. Higher doses induced long-term running of all termites without stops necessary to perform vibratory behaviour. Surprisingly, even crushed worker heads led to low (but significant) increases in the alarm responses, suggesting that other unknown compound in the worker's head is perceived and answered by termites. Our results demonstrate the existence of different alarm levels in termites, with lower levels being communicated through vibratory signals, and higher levels causing general alarm or retreat being communicated through the alarm pheromone. PMID- 26538634 TI - Bridging Translation by Improving Preclinical Study Design in AKI. AB - Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development. PMID- 26538636 TI - Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer. AB - Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120 kb upstream of the Mrf4-Myf5 locus. An enhancer, located at -57/-58 kb from Myf5, is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles. Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element. Myogenic progenitor cells that will form the future muscle masses of the limbs express the factors necessary for Myf5 activation when they delaminate from the hypaxial dermomyotome and migrate into the forelimb bud, however they do not activate Myf5 and the myogenic programme until they have populated the prospective muscle masses. We show that Msx1 and Meox2 homeodomain-containing transcription factors bind in vitro and in vivo to specific sites in the 145-bp element, and are implicated in fine-tuning activation of Myf5 in the forelimb. Msx1, when bound between Pax and Six sites, prevents the binding of these key activators, thus inhibiting transcription of Myf5 and consequent premature myogenic differentiation. Meox2 is required for Myf5 activation at the onset of myogenesis via direct binding to other homeodomain sites in this sequence. Thus, these homeodomain factors, acting in addition to Pax3 and Six1/4, fine-tune the entry of progenitor cells into myogenesis at early stages of forelimb development. PMID- 26538637 TI - Muscle activation during maximal effort tasks: evidence of the selective forces that shaped the musculoskeletal system of humans. AB - The selective forces that played a role in the evolution of the musculoskeletal system of the genus Homo have long been debated and remain poorly understood. In this investigation, we introduce a new approach for testing alternative hypotheses. Our analysis is based on the premise that natural selection can be expected to have resulted in muscles that are large enough to achieve necessary levels of maximum performance in essential behaviors, but not larger. We used surface electromyography in male subjects to identify maximum activation levels in 13 muscles of the back and leg during eight behaviors that have been suggested to have been important to foraging, hunting and fighting performance in early humans. We asked two questions: (1) what behaviors produce maximum activation in each of the investigated muscles and (2) are there specific behaviors that elicit maximum recruitment from all or most of the muscles? We found that in eight of the 13 muscles, the highest activity occurred during maximal effort vertical jumping (i.e. whole-body acceleration). Punching produced the highest median activity in the other five muscles. Together, jumping and punching accounted for 73% of the incidences of maximum activity among all of the muscles and from all of the subjects. Thus, the size of the muscles of the back and leg appear to be more related to the demands of explosive behaviors rather than those of high speed sprinting or sustained endurance running. These results are consistent with the hypothesis that selection on aggressive behavior played an important role in the evolution of the genus Homo. PMID- 26538638 TI - Tarantulas (Araneae: Theraphosidae) use different adhesive pads complementarily during climbing on smooth surfaces: experimental approach in eight arboreal and burrower species. AB - Tarantulas are large spiders with adhesive setae on their legs, which enable them to climb on smooth vertical surfaces. The mechanism proposed to explain adhesion in tarantulas is anisotropic friction, where friction is higher when the leg pushes than when it pulls. However, previous studies and measurements of adhesion in theraphosids were performed using dead specimens. To test their ability to climb, we studied static friction of live theraphosid spiders on different surfaces and at different inclines. We compared burrower with arboreal species to test the hypothesis of higher friction in arboreal tarantulas. We found a complementary participation of claw tufts and scopula of anterior and posterior legs when the tarantula climbs. The mechanics of climbing in association with the biological characteristics of the species are discussed. PMID- 26538639 TI - Epithelial topography for repetitive tooth formation. AB - During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2(+) cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2(+)/Sox9(+) cells. PMID- 26538640 TI - Predictive Coding: How Many Faces? PMID- 26538641 TI - Irregular Speech Rate Dissociates Auditory Cortical Entrainment, Evoked Responses, and Frontal Alpha. AB - The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features. SIGNIFICANCE STATEMENT: The entrainment of rhythmic auditory cortical activity to the speech envelope is considered to be critical for hearing. Previous work has proposed divergent views in which entrainment reflects either early evoked responses related to sound encoding or high-level processes related to expectation or cognitive selection. Using a manipulation of speech rate, we dissociated auditory entrainment at different time scales. Specifically, our results suggest that delta entrainment is controlled by frontal alpha mechanisms and thus support the notion that rhythmic auditory cortical entrainment is shaped by top-down mechanisms. PMID- 26538642 TI - Dopamine D1 Binding Potential Predicts Fusiform BOLD Activity during Face Recognition Performance. AB - The importance of face memory in humans and primates is well established, but little is known about the neurotransmitter systems involved in face recognition. We tested the hypothesis that face recognition is linked to dopamine (DA) activity in fusiform gyrus (FFG). DA availability was assessed by measuring D1 binding potential (BP) during rest using PET. We further assessed blood-oxygen level-dependent (BOLD) signal change while subjects performed a face-recognition task during fMRI scanning. There was a strong association between D1 BP and BOLD activity in FFG, whereas D1 BP in striatal and other extrastriatal regions were unrelated to neural activity in FFG. These results suggest that D1 BP locally modulates FFG function during face recognition. Observed relationships among D1 BP, BOLD activity, and face-recognition performance further suggest that D1 receptors place constraints on the responsiveness of FFG neurons. SIGNIFICANCE STATEMENT: The importance of face memory in humans and primates is well established, but little is known about the neurotransmitter systems involved in face recognition. Our work shows a role for a specific neurotransmitter system in face memory. PMID- 26538643 TI - Brain Connectivity Associated with Muscle Synergies in Humans. AB - The human brain is believed to simplify the control of the large number of muscles in the body by flexibly combining muscle coordination patterns, termed muscle synergies. However, the neural connectivity allowing the human brain to access and coordinate muscle synergies to accomplish functional tasks remains unknown. Here, we use a surprising pair of synergists in humans, the flexor hallucis longus (FHL, a toe flexor) and the anal sphincter, as a model that we show to be well suited in elucidating the neural connectivity underlying muscle synergy control. First, using electromyographic recordings, we demonstrate that voluntary FHL contraction is associated with synergistic anal sphincter contraction, but voluntary anal sphincter contraction occurs without FHL contraction. Second, using fMRI, we show that two important medial wall motor cortical regions emerge in relation to these tasks: one located more posteriorly that preferentially activates during voluntary FHL contraction and one located more anteriorly that activates during both voluntary FHL contraction as well as voluntary anal sphincter contraction. Third, using transcranial magnetic stimulation, we demonstrate that the anterior region is more likely to generate anal sphincter contraction than FHL contraction. Finally, using a repository resting-state fMRI dataset, we demonstrate that the anterior and posterior motor cortical regions have significantly different functional connectivity with distinct and distant brain regions. We conclude that specific motor cortical regions in humans provide access to different muscle synergies, which may allow distinct brain networks to coordinate muscle synergies during functional tasks. SIGNIFICANCE STATEMENT: How the human nervous system coordinates activity in a large number of muscles is a fundamental question. The brain and spinal cord are believed to simplify the control of muscles by grouping them into functional units called muscle synergies. Motor cortex is involved in activating muscle synergies; however, the motor cortical connections that regulate muscle synergy activation are unknown. Here, we studied pelvic floor muscle synergies to elucidate these connections in humans. Our experiments confirmed that distinct motor cortical regions activate different muscle synergies. These regions have different connectivity to distinct brain networks. Our results are an important step forward in understanding the cortical control of human muscles synergies, and may also have important clinical implications for understanding movement dysfunction. PMID- 26538646 TI - Is the Cortical Deficit in Amblyopia Due to Reduced Cortical Magnification, Loss of Neural Resolution, or Neural Disorganization? AB - The neural basis of amblyopia is a matter of debate. The following possibilities have been suggested: loss of foveal cells, reduced cortical magnification, loss of spatial resolution of foveal cells, and topographical disarray in the cellular map. To resolve this we undertook a population receptive field (pRF) functional magnetic resonance imaging analysis in the central field in humans with moderate to-severe amblyopia. We measured the relationship between averaged pRF size and retinal eccentricity in retinotopic visual areas. Results showed that cortical magnification is normal in the foveal field of strabismic amblyopes. However, the pRF sizes are enlarged for the amblyopic eye. We speculate that the pRF enlargement reflects loss of cellular resolution or an increased cellular positional disarray within the representation of the amblyopic eye. SIGNIFICANCE STATEMENT: The neural basis of amblyopia, a visual deficit affecting 3% of the human population, remains a matter of debate. We undertook the first population receptive field functional magnetic resonance imaging analysis in participants with amblyopia and compared the projections from the amblyopic and fellow normal eye in the visual cortex. The projection from the amblyopic eye was found to have a normal cortical magnification factor, enlarged population receptive field sizes, and topographic disorganization in all early visual areas. This is consistent with an explanation of amblyopia as an immature system with a normal complement of cells whose spatial resolution is reduced and whose topographical map is disordered. This bears upon a number of competing theories for the psychophysical defect and affects future treatment therapies. PMID- 26538644 TI - microRNA-33 Regulates ApoE Lipidation and Amyloid-beta Metabolism in the Brain. AB - Dysregulation of amyloid-beta (Abeta) metabolism is critical for Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Abeta metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Abeta levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new therapeutic targets for AD. Here, we demonstrate that microRNA-33 (miR-33) regulates ABCA1 and Abeta levels in the brain. Overexpression of miR-33 impaired cellular cholesterol efflux and dramatically increased extracellular Abeta levels by promoting Abeta secretion and impairing Abeta clearance in neural cells. In contrast, genetic deletion of mir-33 in mice dramatically increased ABCA1 levels and ApoE lipidation, but it decreased endogenous Abeta levels in cortex. Most importantly, pharmacological inhibition of miR-33 via antisense oligonucleotide specifically in the brain markedly decreased Abeta levels in cortex of APP/PS1 mice, representing a potential therapeutic strategy for AD. SIGNIFICANCE STATEMENT: Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to Abeta metabolism and Alzheimer's disease (AD). Brain lipid metabolism is largely separated from the periphery due to blood-brain barrier and different repertoire of lipoproteins. Therefore, identifying the novel regulatory mechanism of brain lipid metabolism may provide a new therapeutic strategy for AD. Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown. Here, we demonstrate that inhibition of microRNA-33 increases lipidation of brain ApoE and reduces Abeta levels by inducing ABCA1. We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce Abeta levels via pharmacological inhibition of microRNA in vivo. PMID- 26538645 TI - Cell-Permeable Peptide Targeting the Nrf2-Keap1 Interaction: A Potential Novel Therapy for Global Cerebral Ischemia. AB - The current study examined efficacy of a small Tat (trans-activator of transcription)-conjugated peptide activator of the Nrf2 (nuclear factor-E2 related factor-2) antioxidant/cell-defense pathway as a potential injury specific, novel neuroprotectant against global cerebral ischemia (GCI). A competitive peptide, DEETGE-CAL-Tat, was designed to facilitate Nrf2 activation by disrupting interaction of Nrf2 with Keap1 (kelch-like ECH-associated protein 1), a protein that sequesters Nrf2 in the cytoplasm and thereby inactivates it. The DEETGE-CAL-Tat peptide contained the critical sequence DEETGE for the Nrf2 Keap1 interaction, the cell transduction domain of the HIV-Tat protein, and the cleavage sequence of calpain, which is sensitive to Ca(2+) increase and allows injury-specific activation of Nrf2. Using an animal model of GCI, we demonstrated that pretreatment with the DEETGE-CAL-Tat peptide markedly decreased Nrf2 interaction with Keap1 in the rat hippocampal CA1 region after GCI, and enhanced Nrf2 nuclear translocation and DNA binding. The DEETGE-CAL-Tat peptide also induced Nrf2 antioxidant/cytoprotective target genes, reduced oxidative stress, and induced strong neuroprotection and marked preservation of hippocampal dependent cognitive function after GCI. These effects were specific as control peptides lacked neuroprotective ability. Intriguingly, the DEETGE-CAL-Tat peptide effects were also injury specific, as it had no effect upon neuronal survival or cognitive performance in sham nonischemic animals. Of significant interest, peripheral, postischemia administration of the DEETGE-CAL-Tat peptide from days 1 9 after GCI also induced robust neuroprotection and strongly preserved hippocampal-dependent cognitive function. Based on its robust neuroprotective and cognitive-preserving effects, and its unique injury-specific activation properties, the DEETGE-CAL-Tat peptide represents a novel, and potentially promising new therapeutic modality for the treatment of GCI. SIGNIFICANCE STATEMENT: The current study demonstrates that DEETGE-CAL-Tat, a novel peptide activator of a key antioxidant gene transcription pathway in the hippocampus after global cerebral ischemia, can exert robust neuroprotection and preservation of cognitive function. A unique feature of the peptide is that its beneficial effects are injury specific. This feature is attractive as it targets drug activation specifically in the site of injury, and likely would lead to a reduction of undesirable side effects if translatable to the clinic. Due to its injury-specific activation, robust neuroprotection, and cognitive-preserving effects, this novel peptide may represent a much-needed therapeutic advance that could have efficacy in the treatment of global cerebral ischemia. PMID- 26538647 TI - An Endocytic Scaffolding Protein together with Synapsin Regulates Synaptic Vesicle Clustering in the Drosophila Neuromuscular Junction. AB - Many endocytic proteins accumulate in the reserve pool of synaptic vesicles (SVs) in synapses and relocalize to the endocytic periactive zone during neurotransmitter release. Currently little is known about their functions outside the periactive zone. Here we show that in the Drosophila neuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocalizes during the SV cycle and forms a functional complex with the SV-associated phosphoprotein synapsin, previously implicated in SV clustering. This direct interaction is strongly enhanced under phosphorylation-promoting conditions and is essential for proper localization of synapsin at NMJs. In a dap160 rescue mutant lacking the interaction between Dap160 and synapsin, perturbed reclustering of SVs during synaptic activity is observed. Our data indicate that in addition to the function in endocytosis, Dap160 is a component of a network of protein-protein interactions that serves for clustering of SVs in conjunction with synapsin. During the SV cycle, Dap160 interacts with synapsin dispersed from SVs and helps direct synapsin back to vesicles. The proteins function in synergy to achieve efficient clustering of SVs in the reserve pool. SIGNIFICANCE STATEMENT: We provide the first evidence for the function of the SH3 domain interaction in synaptic vesicle (SV) organization at the synaptic active zone. Using Drosophila neuromuscular junction as a model synapse, we describe the molecular mechanism that enables the protein implicated in SV clustering, synapsin, to return to the pool of vesicles during neurotransmitter release. We also identify the endocytic scaffolding complex that includes Dap160 as a regulator of the events linking exocytosis and endocytosis in synapses. PMID- 26538648 TI - Sharp Wave Ripples during Visual Exploration in the Primate Hippocampus. AB - Hippocampal sharp-wave ripples (SWRs) are highly synchronous oscillatory field potentials that are thought to facilitate memory consolidation. SWRs typically occur during quiescent states, when neural activity reflecting recent experience is replayed. In rodents, SWRs also occur during brief locomotor pauses in maze exploration, where they appear to support learning during experience. In this study, we detected SWRs that occurred during quiescent states, but also during goal-directed visual exploration in nonhuman primates (Macaca mulatta). The exploratory SWRs showed peak frequency bands similar to those of quiescent SWRs, and both types were inhibited at the onset of their respective behavioral epochs. In apparent contrast to rodent SWRs, these exploratory SWRs occurred during active periods of exploration, e.g., while animals searched for a target object in a scene. SWRs were associated with smaller saccades and longer fixations. Also, when they coincided with target-object fixations during search, detection was more likely than when these events were decoupled. Although we observed high gamma-band field potentials of similar frequency to SWRs, only the SWRs accompanied greater spiking synchrony in neural populations. These results reveal that SWRs are not limited to off-line states as conventionally defined; rather, they occur during active and informative performance windows. The exploratory SWR in primates is an infrequent occurrence associated with active, attentive performance, which may indicate a new, extended role of SWRs during exploration in primates. SIGNIFICANCE STATEMENT: Sharp-wave ripples (SWRs) are high-frequency oscillations that generate highly synchronized activity in neural populations. Their prevalence in sleep and quiet wakefulness, and the memory deficits that result from their interruption, suggest that SWRs contribute to memory consolidation during rest. Here, we report that SWRs from the monkey hippocampus occur not only during behavioral inactivity but also during successful visual exploration. SWRs were associated with attentive, focal search and appeared to enhance perception of locations viewed around the time of their occurrence. SWRs occurring in rest are noteworthy for their relation to heightened neural population activity, temporally precise and widespread synchronization, and memory consolidation; therefore, the SWRs reported here may have a similar effect on neural populations, even as experiences unfold. PMID- 26538649 TI - Endothelial CD36 Contributes to Postischemic Brain Injury by Promoting Neutrophil Activation via CSF3. AB - The scavenger receptor CD36 is a critical factor initiating ischemic brain injury, but the cell type(s) expressing CD36 and responsible for its harmful effects remain unknown. Using bone marrow (BM) chimeras subjected to transient middle cerebral artery occlusion, we found that CD36(-/-) mice transplanted with wild-type (WT) BM (WT->CD36(-/-)) have smaller infarcts (-67%), comparable with those of mice lacking CD36 both in brain and hematogenous cells (CD36(-/-) >CD36(-/-); - 72%). Conversely, WT mice receiving CD36(-/-) BM (CD36(-/-) ->WT) have infarcts similar to WT->WT mice, suggesting that CD36 in the host brain (i.e., in microglia and endothelial cells), and not in hematogenous cells is involved in the damage. As anticipated, postischemic neutrophil infiltration in CD36(-/-) ->CD36(-/-) mice was attenuated. Surprisingly, however, in WT->CD36(-/ ) mice, in which infarcts were small, neutrophil infiltration was large and similar to that of CD36(-/-) ->WT mice, in which infarcts were not reduced. Postischemic neutrophil free radical production was attenuated in WT->CD36(-/-) mice compared with CD36(-/-) ->WT mice, whereas expression of the neutrophil activator colony-stimulating factor 3 (CSF3) was suppressed in CD36(-/-) cerebral endothelial cells, but not microglia. In CD36(-/-) cerebral endothelial cultures exposed to extracts from stroke brains, the upregulation of CSF3, but not neutrophil attractant chemokines, was suppressed. Intracerebroventricular administration of CSF3, 24 h after stroke, reconstituted neutrophil radical production and increased infarct volume in WT->CD36(-/-) mice. The findings identify endothelial cells as a key player in the deleterious effects of CD36 in stroke, and unveil a novel role of endothelial CD36 in enabling neutrophil neurotoxicity through CSF3. SIGNIFICANCE STATEMENT: Ischemic stroke is a leading cause of death and disability worldwide with limited therapeutic options. The inflammatory response initiated by cerebral ischemia-reperfusion contributes to ischemic brain injury and is a potential therapeutic target. Here we report that CD36, an innate immunity receptor involved in the initiation of postischemic inflammation, is a previously unrecognized regulator of neutrophil cytotoxicity. The effect is mediated by endothelial CD36 via upregulation of the neutrophil activator CSF3 in cerebral endothelial cells. Therefore, approaches to modulate cerebral endothelial CD36 signaling or to neutralize CSF3 may provide novel therapeutic opportunities to ameliorate postischemic inflammatory injury. PMID- 26538651 TI - A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits. AB - We were interested in determining whether rostral medial prefrontal cortex (rmPFC) neurons participate in the measurement of conditioned stimulus unconditioned stimulus (CS-US) time intervals during classical eyeblink conditioning. Rabbits were conditioned with a delay paradigm consisting of a tone as CS. The CS started 50, 250, 500, 1000, or 2000 ms before and coterminated with an air puff (100 ms) directed at the cornea as the US. Eyelid movements were recorded with the magnetic search coil technique and the EMG activity of the orbicularis oculi muscle. Firing activities of rmPFC neurons were recorded across conditioning sessions. Reflex and conditioned eyelid responses presented a dominant oscillatory frequency of ~12 Hz. The firing rate of each recorded neuron presented a single peak of activity with a frequency dependent on the CS-US interval (i.e., ~12 Hz for 250 ms, ~6 Hz for 500 ms, and~3 Hz for 1000 ms). Interestingly, rmPFC neurons presented their dominant firing peaks at three precise times evenly distributed with respect to CS start and also depending on the duration of the CS-US interval (only for intervals of 250, 500, and 1000 ms). No significant neural responses were recorded at very short (50 ms) or long (2000 ms) CS-US intervals. rmPFC neurons seem not to encode the oscillatory properties characterizing conditioned eyelid responses in rabbits, but are probably involved in the determination of CS-US intervals of an intermediate range (250-1000 ms). We propose that a variable oscillator underlies the generation of working memories in rabbits. SIGNIFICANCE STATEMENT: The way in which brains generate working memories (those used for the transient processing and storage of newly acquired information) is still an intriguing question. Here, we report that the firing activities of neurons located in the rostromedial prefrontal cortex recorded in alert behaving rabbits are controlled by a dynamic oscillator. This oscillator generated firing frequencies in a variable band of 3-12 Hz depending on the conditioned stimulus-unconditioned stimulus intervals (1 s, 500 ms, 250 ms) selected for classical eyeblink conditioning of behaving rabbits. Shorter (50 ms) and longer (2 s) intervals failed to activate the oscillator and prevented the acquisition of conditioned eyelid responses. This is an unexpected mechanism to generate sustained firing activities in neural circuits generating working memories. PMID- 26538650 TI - A Serotonin Circuit Acts as an Environmental Sensor to Mediate Midline Axon Crossing through EphrinB2. AB - Modulation of connectivity formation in the developing brain in response to external stimuli is poorly understood. Here, we show that the raphe nucleus and its serotonergic projections regulate pathfinding of commissural axons in zebrafish. We found that the raphe neurons extend projections toward midline crossing axons and that when serotonergic signaling is blocked by pharmacological inhibition or by raphe neuron ablation, commissural pathfinding is disrupted. We demonstrate that the serotonin receptor htr2a is expressed on these commissural axons and that genetic knock-down of htr2a disrupts crossing. We further show that knock-down of htr2a or ablation of the raphe neurons increases ephrinB2a protein levels in commissural axons. An ephrinB2a mutant can rescue midline crossing when serotonergic signaling is blocked. Furthermore, we found that regulation of serotonin expression in the raphe neurons is modulated in response to the developmental environment. Hypoxia causes the raphe to decrease serotonin levels, leading to a reduction in midline crossing. Increasing serotonin in the setting of hypoxia restored midline crossing. Our findings demonstrate an instructive role for serotonin in axon guidance acting through ephrinB2a and reveal a novel mechanism for developmental interpretation of the environmental milieu in the generation of mature neural circuitry. SIGNIFICANCE STATEMENT: We show here that serotonin has a novel role in regulating connectivity in response to the developmental environment. We demonstrate that serotonergic projections from raphe neurons regulate pathfinding of crossing axons. The neurons modulate their serotonin levels, and thus alter crossing, in response to the developmental environment including hypoxia. The findings suggest that modification of the serotonergic system by early exposures may contribute to permanent CNS connectivity alterations. This has important ramifications because of the association between premature birth and accompanying hypoxia, and increased risk of autism and evidence associating in utero exposure to some antidepressants and neurodevelopmental disorders. Finally, this work demonstrates that the vertebrate CNS can modulate its connectivity in response to the external environment. PMID- 26538652 TI - Human Auditory Cortex Neurochemistry Reflects the Presence and Severity of Tinnitus. AB - It is not known why tinnitus occurs in some cases of hearing damage but not others. Abnormalities of excitation-inhibition balance could influence whether tinnitus develops and its severity if it does. Animal models of hearing damage, which also produce tinnitus based on behavioral evidence, have identified abnormalities of GABAergic inhibition, both cortically and subcortically. However, the precise relationships of GABA inhibitory changes to tinnitus itself, as opposed to other consequences of hearing damage, remain uncertain. Here, we used magnetic resonance spectroscopy to non-invasively quantify GABA in the left (LAC) and right (RAC) auditory cortices of a group of 14 patients with lateralized tinnitus (eight left ear) and 14 controls matched for age, sex, and hearing. We also explored the potential relationships with other brain metabolites (i.e., choline, N-acetylaspartate, and creatine). The presence of tinnitus was associated with a reduction in auditory cortex GABA concentration. Regardless of tinnitus laterality, post hoc testing indicated reductions that were significant in RAC and nonsignificant in LAC. Tinnitus severity and hearing loss were correlated positively with RAC choline but not GABA. We discuss the results in the context of current models of tinnitus and methodological constraints. SIGNIFICANCE STATEMENT: Permanently affecting one in seven adults, tinnitus lacks both widely effective treatments and adequate understanding of its brain mechanisms. Existing animal models represent tinnitus that may not be distinguishable from homeostatic responses to the auditory insults used to induce it. Human studies can be well controlled in this regard but are usually not (with few even matching control subjects for hearing loss) and are limited in scope as a result of relying solely on non-invasive recording techniques. Here, we exploit recent advances in non-invasive spectroscopic techniques to establish, in a human study tightly controlled for hearing loss and hyperacusis, that tinnitus is associated with a significant reduction in auditory cortex GABA concentration, which has implications for understanding and treatment of the condition. PMID- 26538653 TI - A Convolutional Subunit Model for Neuronal Responses in Macaque V1. AB - The response properties of neurons in the early stages of the visual system can be described using the rectified responses of a set of self-similar, spatially shifted linear filters. In macaque primary visual cortex (V1), simple cell responses can be captured with a single filter, whereas complex cells combine a set of filters, creating position invariance. These filters cannot be estimated using standard methods, such as spike-triggered averaging. Subspace methods like spike-triggered covariance can recover multiple filters but require substantial amounts of data, and recover an orthogonal basis for the subspace in which the filters reside, rather than the filters themselves. Here, we assume a linear nonlinear-linear-nonlinear (LN-LN) cascade model in which the first LN stage consists of shifted ("convolutional") copies of a single filter, followed by a common instantaneous nonlinearity. We refer to these initial LN elements as the "subunits" of the receptive field, and we allow two independent sets of subunits, each with its own filter and nonlinearity. The second linear stage computes a weighted sum of the subunit responses and passes the result through a final instantaneous nonlinearity. We develop a procedure to directly fit this model to electrophysiological data. When fit to data from macaque V1, the subunit model significantly outperforms three alternatives in terms of cross-validated accuracy and efficiency, and provides a robust, biologically plausible account of receptive field structure for all cell types encountered in V1. SIGNIFICANCE STATEMENT: We present a new subunit model for neurons in primary visual cortex that significantly outperforms three alternative models in terms of cross validated accuracy and efficiency, and provides a robust and biologically plausible account of the receptive field structure in these neurons across the full spectrum of response properties. PMID- 26538654 TI - Sustained Arginase 1 Expression Modulates Pathological Tau Deposits in a Mouse Model of Tauopathy. AB - Tau accumulation remains one of the closest correlates of neuronal loss in Alzheimer's disease. In addition, tau associates with several other neurodegenerative diseases, collectively known as tauopathies, in which clinical phenotypes manifest as cognitive impairment, behavioral disturbances, and motor impairment. Polyamines act as bivalent regulators of cellular function and are involved in numerous biological processes. The regulation of the polyamines system can become dysfunctional during disease states. Arginase 1 (Arg1) and nitric oxide synthases compete for l-arginine to produce either polyamines or nitric oxide, respectively. Herein, we show that overexpression of Arg1 using adeno-associated virus (AAV) in the CNS of rTg4510 tau transgenic mice significantly reduced phospho-tau species and tangle pathology. Sustained Arg1 overexpression decreased several kinases capable of phosphorylating tau, decreased inflammation, and modulated changes in the mammalian target of rapamycin and related proteins, suggesting activation of autophagy. Arg1 overexpression also mitigated hippocampal atrophy in tau transgenic mice. Conversely, conditional deletion of Arg1 in myeloid cells resulted in increased tau accumulation relative to Arg1-sufficient mice after transduction with a recombinant AAV-tau construct. These data suggest that Arg1 and the polyamine pathway may offer novel therapeutic targets for tauopathies. PMID- 26538655 TI - Fbxw7 Limits Myelination by Inhibiting mTOR Signaling. AB - An important characteristic of vertebrate CNS development is the formation of specific amounts of insulating myelin membrane on axons. CNS myelin is produced by oligodendrocytes, glial cells that extend multiple membrane processes to wrap multiple axons. Recent data have shown that signaling mediated by the mechanistic target of rapamycin (mTOR) serine/threonine kinase promotes myelination, but factors that regulate mTOR activity for myelination remain poorly defined. Through a forward genetic screen in zebrafish, we discovered that mutation of fbxw7, which encodes the substrate recognition subunit of a SCF ubiquitin ligase that targets proteins for degradation, causes hypermyelination. Among known Fbxw7 targets is mTOR. Here, we provide evidence that mTOR signaling activity is elevated in oligodendrocyte lineage cells of fbxw7 mutant zebrafish larvae. Both genetic and pharmacological inhibition of mTOR function suppressed the excess myelin gene expression resulting from loss of Fbxw7 function, indicating that mTOR is a functionally relevant target of Fbxw7 in oligodendrocytes. fbxw7 mutant larvae wrapped axons with more myelin membrane than wild-type larvae and oligodendrocyte-specific expression of dominant-negative Fbxw7 produced longer myelin sheaths. Our data indicate that Fbxw7 limits the myelin-promoting activity of mTOR, thereby serving as an important brake on developmental myelination. SIGNIFICANCE STATEMENT: Myelin, a specialized, proteolipid-rich membrane that ensheaths and insulates nerve fibers, facilitates the rapid conduction of electrical impulses over long distances. Abnormalities in myelin formation or maintenance result in intellectual and motor disabilities, raising a need for therapeutic strategies designed to promote myelination. The mTOR kinase is a powerful driver of myelination, but the mechanisms that regulate mTOR function in myelination are not well understood. Our studies reveal that Fbxw7, a subunit of a ubiquitin ligase that targets other proteins for degradation, acts as a brake on myelination by limiting mTOR function. These findings suggest that Fbxw7 helps tune the amount of myelin produced during development and raise the possibility that Fbxw7 could be a target of myelin-promoting therapies. PMID- 26538656 TI - REST Regulates Non-Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II. AB - RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non-cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non-cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non-cell-autonomously via SCG2. SIGNIFICANCE STATEMENT: Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell intrinsic and non-cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons. PMID- 26538657 TI - Memory Meets Control in Hippocampal and Striatal Binding of Stimuli, Responses, and Attentional Control States. AB - The human brain encodes experience in an integrative fashion by binding together the various features of an event (i.e., stimuli and responses) into memory "event files." A subsequent reoccurrence of an event feature can then cue the retrieval of the memory file to "prime" cognition and action. Intriguingly, recent behavioral studies indicate that, in addition to linking concrete stimulus and response features, event coding may also incorporate more abstract, "internal" event features such as attentional control states. In the present study, we used fMRI in healthy human volunteers to determine the neural mechanisms supporting this type of holistic event binding. Specifically, we combined fMRI with a task protocol that dissociated the expression of event feature-binding effects pertaining to concrete stimulus and response features, stimulus categories, and attentional control demands. Using multivariate neural pattern classification, we show that the hippocampus and putamen integrate event attributes across all of these levels in conjunction with other regions representing concrete-feature selective (primarily visual cortex), category-selective (posterior frontal cortex), and control demand-selective (insula, caudate, anterior cingulate, and parietal cortex) event information. Together, these results suggest that the hippocampus and putamen are involved in binding together holistic event memories that link physical stimulus and response characteristics with internal representations of stimulus categories and attentional control states. These bindings then presumably afford shortcuts to adaptive information processing and response selection in the face of recurring events. SIGNIFICANCE STATEMENT: Memory binds together the different features of our experience, such as an observed stimulus and concurrent motor responses, into so-called event files. Recent behavioral studies suggest that the observer's internal attentional state might also become integrated into the event memory. Here, we used fMRI to determine the brain areas responsible for binding together event information pertaining to concrete stimulus and response features, stimulus categories, and internal attentional control states. We found that neural signals in the hippocampus and putamen contained information about all of these event attributes and could predict behavioral priming effects stemming from these features. Therefore, medial temporal lobe and dorsal striatum structures appear to be involved in binding internal control states to event memories. PMID- 26538658 TI - Outside Looking In: Landmark Generalization in the Human Navigational System. AB - The use of landmarks is central to many navigational strategies. Here we use multivoxel pattern analysis of fMRI data to understand how landmarks are coded in the human brain. Subjects were scanned while viewing the interiors and exteriors of campus buildings. Despite their visual dissimilarity, interiors and exteriors corresponding to the same building elicited similar activity patterns in the parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA), three regions known to respond strongly to scenes and buildings. Generalization across stimuli depended on knowing the correspondences among them in the PPA but not in the other two regions, suggesting that the PPA is the key region involved in learning the different perceptual instantiations of a landmark. In contrast, generalization depended on the ability to freely retrieve information from memory in RSC, and it did not depend on familiarity or cognitive task in OPA. Together, these results suggest a tripartite division of labor, whereby PPA codes landmark identity, RSC retrieves spatial or conceptual information associated with landmarks, and OPA processes visual features that are important for landmark recognition. SIGNIFICANCE STATEMENT: A central element of spatial navigation is the ability to recognize the landmarks that mark different places in the world. However, little is known about how the brain performs this function. Here we show that the parahippocampal place area (PPA), a region in human occipitotemporal cortex, exhibits key features of a landmark recognition mechanism. Specifically, the PPA treats different perceptual instantiations of the same landmark as representationally similar, but only when subjects have enough experience to know the correspondences among the stimuli. We also identify two other brain regions that exhibit landmark generalization, but with less sensitivity to familiarity. These results elucidate the brain networks involved in the learning and recognition of navigational landmarks. PMID- 26538659 TI - Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia. AB - Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory insula connectivity. MMN to FM tones and functional connectivity together accounted for ~50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. SIGNIFICANCE STATEMENT: Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ~50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia. PMID- 26538661 TI - VPS26A-SNX27 Interaction-Dependent mGluR5 Recycling in Dorsal Horn Neurons Mediates Neuropathic Pain in Rats. AB - Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A and SNX27 expression; VPS26A-SNX27 coprecipitation; and VPS26A-positive, SNX27-positive, and VPS26A-SNX27 double-labeled immunoreactivity in the dorsal horn of Sprague Dawley rats that were all sufficiently ameliorated through the focal knock-down of spinal VPS26A expression. Although the knock-down of spinal SNX27 expression exhibited similar effects, spinal nerve ligation (SNL)-enhanced VPS26A expression remained unaffected. Moreover, SNL also increased membrane-bound and total mGluR5 abundance, VPS26A-bound SNX27 and mGluR5 and mGluR5-bound VPS26A and SNX27 coprecipitation, and mGluR5-positive and VPS26A/SNX27/mGluR5 triple-labeled immunoreactivity in the dorsal horn, and these effects were all attenuated through the focal knock-down of spinal VPS26A and SNX27 expression. Although administration with MPEP adequately ameliorated SNL-associated allodynia, mGluR5 expression, and membrane insertion, SNL-enhanced VPS26A and SNX27 expression were unaffected. Together, these results suggested a role of spinal VPS26A-SNX27 dependent mGluR5 recycling in the development of neuropathic pain. This is the first study that links retromer-associated sorting machinery with the spinal plasticity underlying pain hypersensitivity and proposes the possible pathophysiological relevance of endocytic recycling in pain pathophysiology through the modification of glutamatergic mGluR5 recycling. SIGNIFICANCE STATEMENT: VPS26A-SNX27-dependent mGluR5 recycling plays a role in the development of neuropathic pain. The regulation of the VPS26A-SNX27 interaction that modifies mGluR5 trafficking and expression in the dorsal horn provides a novel therapeutic strategy for pain relief. PMID- 26538662 TI - Hypothesis testing for band size detection of high-dimensional banded precision matrices. AB - Many statistical analysis procedures require a good estimator for a high dimensional covariance matrix or its inverse, the precision matrix. When the precision matrix is banded, the Cholesky-based method often yields a good estimator of the precision matrix. One important aspect of this method is determination of the band size of the precision matrix. In practice, crossvalidation is commonly used; however, we show that crossvalidation not only is computationally intensive but can be very unstable. In this paper, we propose a new hypothesis testing procedure to determine the band size in high dimensions. Our proposed test statistic is shown to be asymptotically normal under the null hypothesis, and its theoretical power is studied. Numerical examples demonstrate the effectiveness of our testing procedure. PMID- 26538660 TI - Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons. AB - The Kv2 family of voltage-gated potassium channel alpha subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K(+) current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell- and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylation-dependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex. SIGNIFICANCE STATEMENT: Neurons within the neocortex are arranged in a laminar architecture and contribute to the input, processing, and/or output of sensory and motor signals in a cell- and layer-specific manner. Neurons of different cortical layers express diverse populations of ion channels and possess distinct intrinsic membrane properties. Here, we show that the Kv2 family members Kv2.1 and Kv2.2 are expressed in distinct cortical layers and pyramidal cell types associated with specific corticostriatal pathways. We find that Kv2.1 and Kv2.2 exhibit distinct responses to acute phosphorylation dependent regulation in brain neurons in situ and in heterologous cells in vitro. These results identify a molecular mechanism that contributes to heterogeneity in cortical neuron ion channel function and regulation. PMID- 26538663 TI - Multicategory angle-based large-margin classification. AB - Large-margin classifiers are popular methods for classification. Among existing simultaneous multicategory large-margin classifiers, a common approach is to learn k different functions for a k-class problem with a sum-to-zero constraint. Such a formulation can be inefficient. We propose a new multicategory angle-based large-margin classification framework. The proposed angle-based classifiers consider a simplex-based prediction rule without the sum-to-zero constraint, and enjoy more efficient computation. Many binary large-margin classifiers can be naturally generalized for multicategory problems through the angle-based framework. Theoretical and numerical studies demonstrate the usefulness of the angle-based methods. PMID- 26538664 TI - Back to basics. PMID- 26538665 TI - An ethicist's commentary on productivity's mark of animal welfare. PMID- 26538666 TI - The lesions of toe tip necrosis in southern Alberta feedlot cattle provide insight into the pathogenesis of the disease. AB - Gross and histologic postmortem studies were performed on the hind feet of feedlot cattle that had, or were free from, lesions of toe tip necrosis. The hind feet of feedlot cattle were collected by 3 veterinary feedlot practices in southern Alberta, Canada. Three studies of these feet were conducted: i) prediction of disease based on the presence or absence of apical white line separation, ii) gross assessment of the distribution and severity of lesions within affected claws, and iii) microscopic evaluation of the distal phalanx and surrounding soft tissues of affected claws. Prediction of toe tip necrosis based on the presence of apical white line separation was statistically significant (P < 0.0001). This, combined with a pattern of lesions indicative of an ascending infection of the distal phalanx and the absence of other lesions, suggests that the pathogenesis involves bacterial infection originating from the most distal aspect of the toe, at the apical white line. PMID- 26538667 TI - Retrospective comparison of costs between medical and surgical treatment of canine pyothorax. AB - This study compared costs of treating dogs with pyothorax medically versus surgically. Medical records from the University of Wisconsin School of Veterinary Medicine were searched for cases of pyothorax that underwent either medical or surgical treatment. Patients undergoing surgery were subdivided into early (ES; < 48 h) and late (LS; > 48 h) surgery groups. Costs and length of stay were compared between treatment groups. Treatment costs were adjusted for inflation. Nineteen dogs were included in analysis; 7 in the medical group (MG), 5 in the ES group, and 7 in the LS group. Total costs were significantly lower in the MG than in the LS group. Total costs were less for the MG than the ES group, and for ES than LS, but the differences did not achieve significance. Preoperative costs were higher in the LS than the ES group. We conclude that surgery for canine pyothorax is less costly if pursued earlier than later. PMID- 26538668 TI - Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs. AB - Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 MUg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation was achieved in all cases. PMID- 26538669 TI - Computed tomography diagnosis of a thoracic and abdominal penetrating foreign body in a dog. AB - A 1.5-year-old, spayed female, mixed-breed dog was presented for hemoabdomen associated with an abdominal mass. Upon presentation bicavitary effusion was diagnosed. A penetrating intra-abdominal wooden foreign body was identified using computed tomography. This case describes a thoracic penetrating wooden foreign body causing bicavitary effusion following migration into the retroperitoneal space. PMID- 26538670 TI - Primary portal vein hypoplasia and SLC2A9 mutation associated with urate urolithiasis in a Spanish water dog. AB - This report describes a Spanish water dog with an ammonium urate urethrolith which was diagnosed with primary portal vein hypoplasia and was found to be homozygous for the mutated SLC2A9 gene. This is the first Spanish water dog described with the SLC2A9 mutation and the first case of concurrent portal vascular abnormalities and SLC2A9 mutation. PMID- 26538671 TI - Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP). AB - A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs. PMID- 26538672 TI - Use of gentamicin sulfate-impregnated sponges as adjuvant therapy for the treatment of chronic foreign body associated sternal osteomyelitis in a dog. AB - A 2-year-old Labrador retriever dog was referred for evaluation of parasternal chronic draining sinus tracts associated with sternal osteomyelitis secondary to the presence of a residual wooden foreign body. The use of gentamicin-impregnated collagen sponges as adjunctive therapy to osteomyelitis treatment is reported herein. PMID- 26538673 TI - Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse. AB - This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor. PMID- 26538674 TI - Concurrent cranial mediastinal Blastomyces granuloma and carcinoma with cranial vena caval syndrome in a dog. AB - This report describes an unusual progression of blastomycosis in a dog with concurrent mediastinal carcinoma. The dog was evaluated for respiratory distress. Diagnostic results revealed chylothorax and a cranial vena caval thrombus. Histopathology of the cranial mediastinal mass diagnosed mediastinal carcinoma and fungal granuloma. Intercurrent disease may complicate the clinical presentation and clinical course of blastomycosis. PMID- 26538675 TI - Chronic active interstitial pancreatitis as a cause of transverse colonic obstruction and colic in a horse. AB - A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. PMID- 26538676 TI - Canine nail bed keratoacanthoma diagnosed by immunohistochemical analysis. AB - A 10-year-old, Shih Tzu dog was presented with an enlarged, curled 2nd nail in the left forelimb. Digital amputation was performed and the mass was diagnosed as a nail bed keratoacanthoma (infundibular keratinizing acanthoma) histopathologically. There was no recurrence postoperatively. This is the first case report of a canine nail bed keratoacanthoma diagnosed by histologic and immunohistochemical examination including Ki-67 and p53 expression. PMID- 26538677 TI - Multiple tarsal luxations in 2 Holstein heifers. AB - Two Holstein heifers were referred for non-weight bearing lameness. The physical examination and radiographic findings were diagnostic of tarsal luxation. Treatment and outcome are reported. A closed reduction was successfully performed in 1 heifer. The second animal was euthanized after attempts to reduce and stabilize the joint. PMID- 26538678 TI - The economics of veterinarians in government, industry, and academe. PMID- 26538679 TI - Diagnostic Ophthalmology. Corneal lesion in a cat. PMID- 26538680 TI - Intimate Partner Violence in Young Adulthood: Narratives of Persistence and Desistance. AB - Prior research on patterns of intimate partner violence (IPV) has documented changes over time, but few studies have focused directly on IPV desistance processes. This analysis identifies unique features of IPV, providing a rationale for the focus on this form of behavior cessation. We develop a life-course perspective on social learning as a conceptual framework and draw on qualitative interviews (n = 89) elicited from a sample of young adults who participated in a larger longitudinal study (Toledo Adolescent Relationships Study). The respondents' backgrounds reflected a range of persistence and desistance from IPV perpetration. Our analyses revealed that relationship-based motivations and changes were central features of the narratives of successful desisters, whether articulated as a stand-alone theme or in tandem with other potential "hooks" for change. The analysis provides a counterpoint to individualistic views of desistance processes, highlighting ways in which social experiences foster attitude shifts and associated behavioral changes that respondents tied to this type of behavior change. The analyses of persisters and those for whom change seemed to be a work in progress provide points of contrast and highlight barriers that limit a respondent's desistance potential. We describe implications for theories of desistance as well as for IPV prevention and intervention efforts. PMID- 26538681 TI - Electrochemical transformation of thichloroethylene in groundwater by Ni containing cathodes. AB - In this study, we evaluate the use of different stainless steel (SS) materials as cost-effective cathode materials for electrochemical transformation of trichloroethylene (TCE) in contaminated groundwater. Ni, which is present in certain SS, has low hydrogen overpotential that promotes fast formation of atomic hydrogen and, therefore, its content can enhance hydrodechlorination (HDC). We a flow-through electrochemical reactor with a SS cathode followed by an anode. The performance of Ni containing foam cathodes (Fe/Ni and Ni foam) was also evaluated for electrochemical transformation of TCE in groundwater. SS type 316 (12% Ni) removed 61.7% of TCE compared to 52.6% removed by SS 304 (9.25% Ni) and 37.5% removed by SS 430 (0.75% Ni). Ni foam cathode produced the highest TCE removal rate (68.4%) compared with other cathodes. The slightly lower performance of SS type 316 mesh is balanced by the reduction in treatment costs for larger-scale systems. The results prove that Ni content in SS highly influences TCE removal rate. PMID- 26538683 TI - Silicon Detector System for High Rate EXAFS Applications. AB - A multichannel silicon pad detector for EXAFS (Extended X-ray Absorption Fine Structure) applications has been designed and built. The X-ray spectroscopic measurements demonstrate that an adequate energy resolution of 230 eV FWHM (corresponding to 27 rms electrons in silicon) can be achieved reliably at -35 degrees C. A resolution of 190 eV FWHM (corresponding to 22 rms electrons) has been obtained from individual pads at -35 degrees C. At room temperature (25 degrees C) an average energy resolution of 380 eV FWHM is achieved and a resolution of 350 eV FWHM (41 rms electrons) is the best performance. A simple cooling system constituted of Peltier cells is sufficient to reduce the reverse currents of the pads and their related shot noise contribution, in order to achieve resolutions better than 300 eV FWHM which is adequate for the EXAFS applications. PMID- 26538682 TI - Bioinspired Polarization Imaging Sensors: From Circuits and Optics to Signal Processing Algorithms and Biomedical Applications: Analysis at the focal plane emulates nature's method in sensors to image and diagnose with polarized light. AB - In this paper, we present recent work on bioinspired polarization imaging sensors and their applications in biomedicine. In particular, we focus on three different aspects of these sensors. First, we describe the electro-optical challenges in realizing a bioinspired polarization imager, and in particular, we provide a detailed description of a recent low-power complementary metal-oxide semiconductor (CMOS) polarization imager. Second, we focus on signal processing algorithms tailored for this new class of bioinspired polarization imaging sensors, such as calibration and interpolation. Third, the emergence of these sensors has enabled rapid progress in characterizing polarization signals and environmental parameters in nature, as well as several biomedical areas, such as label-free optical neural recording, dynamic tissue strength analysis, and early diagnosis of flat cancerous lesions in a murine colorectal tumor model. We highlight results obtained from these three areas and discuss future applications for these sensors. PMID- 26538684 TI - Compact CT/SPECT Small-Animal Imaging System. AB - We have developed a dual-modality CT/SPECT imaging system for small-animal imaging applications. The X-ray system comprises a commercially available micro focus X-ray tube and a CCD-based X-ray camera. X-ray transmission measurements are performed based on cone-beam geometry. Individual projections are acquired by rotating the animal about a vertical axis in front of the CCD detector. A high resolution CT image is obtained after reconstruction using an ordered subsets expectation maximization (OS-EM) reconstruction algorithm. The SPECT system utilizes a compact semiconductor camera module previously developed in our group. The module is mounted perpendicular to the X-ray tube/CCD combination. It consists of a 64*64 pixellated CdZnTe detector and a parallel-hole tungsten collimator. The field of view is 1 square inch. Planar projections for SPECT reconstruction are obtained by rotating the animal in front of the detector. Gamma-ray and X-ray images are presented of phantoms and mice. Procedures for merging the anatomical and functional images are discussed. PMID- 26538685 TI - Arrays of Segmented, Tapered Light Guides for Use with Large, Planar Scintillation Detectors. AB - Metabolic imaging techniques can potentially improve detection and diagnosis of cancer in women with radiodense and/or fibrocystic breasts. Our group has previously developed a high-resolution positron emission tomography imaging and biopsy device (PEM-PET) to detect and guide the biopsy of suspicious breast lesions. Initial testing revealed that the imaging field-of-view (FOV) of the scanner was smaller than the physical size of the detector's active area, which could hinder sampling of breast areas close to the chest wall. The purpose of this work was to utilize segmented, tapered light guides for optically coupling the scintillator arrays to arrays of position-sensitive photomultipliers to increase both the active FOV and identification of individual scintillator elements. Testing of the new system revealed that the optics of these structures made it possible to discern detector elements from the complete active area of the detector face. In the previous system the top and bottom rows and left and right columns were not identifiable. Additionally, use of the new light guides increased the contrast of individual detector elements by up to 129%. Improved element identification led to a spatial resolution increase by approximately 12%. Due to attenuation of light in the light guides the detector energy resolution decreased from 18.5% to 19.1%. Overall, these improvements should increase the field-of-view and spatial resolution of the dedicated breast-PET system. PMID- 26538686 TI - Role of Oxidative and Nitrosative Stress in Pathophysiology of Toxic Epidermal Necrolysis and Stevens Johnson Syndrome-A Pilot Study. AB - BACKGROUND: Oxidative and nitrosative stress caused by drug metabolism may be a trigger for keratinocyte apoptosis in the epidermis seen in toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS). AIMS: To estimate oxidative damage in the serum and to examine the role of nitric oxide in mediating epidermal damage in patients with TEN and SJS. MATERIALS AND METHODS: A prospective study was conducted among TEN and SJS patients and controls in a tertiary care center between January 2006 and February 2010. Patients with a maculopapular drug rash without detachment of skin constituted the control group 1 (drug exposed). Patients without a drug rash constituted the control group 2 (drug unexposed). The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were measured. Two-group comparison with the non parametric Mann-Whitney U test was used. Significance of differences if any was established using Pearson's Chi-square test. RESULTS: Ten patients in the SJS-TEN group (study group), 8 patients in control group 1 and 7 patients in control group 2 were included. More than one drug was implicated in 4/10 patients in group 1 and 3/8 patients in group 2. SCORTEN of 0, 1 and 3 at admission were seen in 2, 6 and 2 patients, respectively. The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were not significantly increased in the study group when compared to the controls. CONCLUSIONS: There was no elevation of oxidative stress markers in patients with TEN and SJS as compared to the control population. PMID- 26538687 TI - Interleukin-1 Gene Polymorphisms and their Relation with NFkappaB Expression and Histopathological Features in Psoriasis. AB - BACKGROUND: Psoriasis is a chronic inflammatory disease driven by exaggerated production of pro-inflammatory cytokines and interleukins. Various genetic polymorphisms including IL-1 are implicated in pathogenesis of psoriasis. The exact role of IL-1 gene polymorphisms and their interaction with NFkappaB is not yet determined. We aimed to study various genetic polymorphisms of IL-1 in psoriasis and their influence on NFkappaB and histopathological features. MATERIALS AND METHODS: 112 newly diagnosed cases of psoriasis vulgaris were included in this prospective study. Histology was done on sections and genotyping was done for the IL-1beta and IL-1 receptor antagonist (IL-1RA) genetic polymorphisms. In addition, NFkappaB immunostaining was performed on 89 sections and the intensity of staining was evaluated in the epidermis, basal cells, and the lymphocytes. RESULTS: A strong association of IL-1beta 511 C/T polymorphism was found with both genotypes and alleles in psoriasis. A strong correlation was also detected between the IL-1beta genotype and the grade of NFkappaB immunostaining in the epidermis (P = 0.012). The grade of NFkappaB lymphocyte staining showed a strong correlation with the IL-1RA genotype (P = 0.025) but not with the IL-1beta genotype (P = 0.226). The genetic polymorphisms did not show any correlation with the histological features. CONCLUSIONS: IL-1 genetic polymorphisms may not play a very direct role in pathogenesis of psoriasis. However, their interaction with NFkappaB appears to be a significant factor in this direction as NFkappaB is activated by pro-inflammatory genetic polymorphisms and therefore may influence the severity of psoriasis. PMID- 26538688 TI - Alterations in Lipid Metabolism and Antioxidant Status in Lichen Planus. AB - BACKGROUND: Lichen planus (LP), a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV) risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis. AIM AND OBJECTIVE: The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients. MATERIALS AND METHODS: The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls) visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP), malondialdehyde (MDA), and catalase (CAT) activity. RESULTS: Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) along with decreased levels of high-density lipoprotein cholesterol (HDL-C) in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C) and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96) was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = -0.76) was seen between CAT activity and LP duration. CONCLUSION: Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in oxidative stress and imbalance in the antioxidant defense mechanisms in LP may play a role in the pathogenesis of LP. PMID- 26538689 TI - Role of Depression, Anxiety and Stress in Patients with Oral Lichen Planus: A Pilot Study. AB - CONTEXT: Lichen planus is a psychosomatic disease. Higher frequency of psychiatric symptoms, poor quality of life, higher level of anxiety and neuroendocrine and immune dysregulations, all these factors, will enhance the exacerbation of the disease. AIMS: The present study was to assess depression, anxiety and stress levels in patients with oral lichen planus. MATERIALS AND METHODS: The psychometric evaluation using the Depression Anxiety Stress Scale (DASS)-42 questionnaire was carried out, by the same investigator on all members of group 1 (Oral Lichen Planus) and group 2 (Control). DASS-42 questionnaire consists of 42 symptoms divided into three subscales of 14 items: Depression scale, anxiety scale, and stress scale. STATISTICAL ANALYSIS USED: The Student t test was used to determine statistical difference for both the groups and to evaluate for significant relationships among variables. RESULTS: Psychological assessment using DASS-42 reveals lichen planus patients showed higher frequency of psychiatric co morbidities like depression, anxiety and stress compared to control group. CONCLUSIONS: This study has provided evidence that the DASS-42 questionnaire is internally consistent and valid measures of depression, anxiety, and stress. Psychiatric evaluation can be considered for patients with oral lichen planus with routine treatment protocols are recommended. DASS-42 Questionnaire can also be used to determine the level of anxiety, stress and depression in diseases of the oral mucosa like recurrent apthous stomatitis, burning mouth syndrome and TMD disorders. PMID- 26538690 TI - Comparing The Efficacy of Hematoxylin and Eosin, Periodic Acid Schiff and Fluorescent Periodic Acid Schiff-Acriflavine Techniques for Demonstration of Basement Membrane in Oral Lichen Planus: A Histochemical Study. AB - BACKGROUND: Basement membrane (BM) is a thick sheet of extracellular matrix molecules, upon which epithelial cells attach. Various immunohistochemical studies in the past have been carried out but these advanced staining techniques are expensive and not feasible in routine laboratories. Although hematoxylin and eosin (H-E) is very popular among pathologists for looking at biopsies, the method has some limitations. This is where special stains come handy. AIMS AND OBJECTIVES: The aim of the present study was to demonstrate and compare the efficacy of H-E, periodic acid Schiff (PAS) and fluorescent periodic acid acriflavine staining techniques for the basement membrane and to establish a histochemical stain which could be cost effective, less time consuming, and unambiguous for observation of the basement membrane zone. MATERIALS AND METHODS: A total number of 40 paraffin-embedded tissue sections of known basement membrane containing tissues including 10 - Normal oral mucosa (NOM) and 30 - oral lichen planus (OLP) were considered in the study. Four-micron-thick sections of each block were cut and stained with H-E stain, PAS and fluorescent periodic acid acriflavine stain. Sections were evaluated by three oral pathologists independently for continuity, contrast and pattern. RESULTS: Though all the three stains showed favorable features at different levels, acriflavine stain was better than the other stains in demonstrating BM continuity, contrast and also the pattern followed by PAS stain. Acriflavine stain was the better in demonstrating a fibrillar pattern of a BM. Acriflavine stains a BM distinctly and is less time consuming and easy to carry out using readily available dyes as compared to other stains. CONCLUSION: The continuity and contrast along with the homogenous pattern and the afibrillar pattern of the BM was better demonstrated by acriflavine followed by the PAS stain. PMID- 26538691 TI - Concurrent Presentation of Erythrodermic Lichen Planus and Squamous Cell Carcinoma: Coincidence or Malignant Transformation? AB - Lichen planus is a common papulosquamous disorder affecting about 1-2% of the population, neoplastic transformation of cutaneous lichen planus lesions occurs very rarely. A 40 year old female patient presented with a 1 year history of developing multiple, itchy, pigmented lesions over both lower legs which gradually spread to involve the whole body. A few tense bullae were seen on the extremities. An erythematous fleshy lesion was seen on the upper aspect of the left buttock. Skin biopsy from a plaque on the right forearm showed features suggestive of lichen planus. Skin biopsy of a bullae showed a sub epidermal bulla filled with a mixed inflammatory infiltrate. Direct immunofluorescence revealed no immunoreactants along the basement membrane zone. A diagnosis of erythrodermic lichen planus with bullous lichen planus was made. Biopsy of fleshy lesion of left buttock revealed a moderately differentiated squamous cell carcinoma. Erythrodermic lichen planus with bullous lesions and secondary squamous cell carcinoma; these occurences in a single patient is extremely rare and has not been previously reported to the best of our knowledge. PMID- 26538692 TI - Decrease in "Hamilton Rating Scale for Depression" Following Isotretinoin Therapy in Acne: An Open-Label Prospective Study. AB - BACKGROUND: Acne is a common disorder among adolescents and young adults causing a considerable psychological impact including anxiety and depression. Isotretinoin, a synthetic oral retinoid is very effective in the treatment of moderate to severe acne. But there have been many reports linking isotretinoin to depression and suicide though no clear proof of association has been established so far. OBJECTIVE: To determine whether oral isotretinoin increases the risk of depression in patients with moderate to severe acne. MATERIALS AND METHODS: One hundred and fifty patients with moderate to severe acne were treated with oral isotretinoin 0.5 mg/kg/day for a period of 3 months. Their acne and depression scoring was done at baseline and then every month for the first 3 months and then at 6 months. RESULTS: We found that the acne scoring reduced from 3.11 +/- 0.49 to 0.65 +/- 0.62 (P = < 0.001) at the end of 3 months. Also, the depression scoring decreased significantly from 3.89 +/- 4.9 at the beginning of study to 0.45 +/- 1.12 (P < 0.001) at the end of 3 months. Both the acne and depression scores continued to remain low at the end of 6 months at 0.5 +/- 0.52 (P = < 0.001) and 0.18 +/- 0.51 (P = < 0.001), respectively. CONCLUSIONS: Our study proves that oral isotretinoin causes significant clearance of acne lesions. It causes significant reduction in depression scores and is not associated with an increased incidence of depression or suicidal tendencies. PMID- 26538693 TI - Prevalence of Skin Changes in Diabetes Mellitus and its Correlation with Internal Diseases: A Single Center Observational Study. AB - BACKGROUND AND AIM: This single-center observational cross-sectional study has been done in an attempt to find out the prevalence of various skin manifestations in diabetes patients (DM) and their correlation with diabetes control and complications. MATERIALS AND METHODS: Skin manifestations present over 12 months among those attend diabetes clinic were included in the study. Apart from demographic data and type, patients were also screened for micro vascular complications and control of diabetes over last 3 months. RESULTS AND DISCUSSION: Sixty (n = 60) diabetes patisents (Type 1 DM, 9 patients and Type 2 DM 51 patients) have been found to have various skin lesions. Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group were present in 50 (83.33%) patients. Pyoderma, diabetic dermopathy, and pruritus without skin lesions were found to be most common manifestations in infective, vascular and miscellaneous group, respectively. Higher level of HB1AC was found in patient with diabetic bulla (10.5 +/- 0), scleredema (9.75 +/- 0.77), lichen planus (9.3 +/- 1.6), and acanthosis nigricans (9.15 +/- 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). However, no association of any kind of skin manifestation with DM with other microangiopathic complications was found in this study. PMID- 26538694 TI - Successful Repigmentation of Vitiligo after Allogeneic Bone Marrow Transplantation for Hodgkin's Lymphoma by Autologous Noncultured Melanocyte keratinocyte Transplantation. AB - The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin's lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation. PMID- 26538695 TI - Efficacy of Punch Elevation Combined with Fractional Carbon Dioxide Laser Resurfacing in Facial Atrophic Acne Scarring: A Randomized Split-face Clinical Study. AB - BACKGROUND: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. MATERIALS AND METHODS: Forty-two Iranian subjects (age range 18-55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. RESULTS: The mean +/- SD age of patients was 23.4 +/- 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). CONCLUSION: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID- 26538696 TI - A Clinico-Bacteriological Study of Pyodermas at a Tertiary Health Center in Southwest Rajasthan. AB - BACKGROUND: The spectrum of pyoderma changes constantly, and so does the antibiotic susceptibility pattern. AIMS: This study was done to assess the magnitude and clinical patterns of pyodermas, their causative micro-organisms, and the antibiotic susceptibility patterns. MATERIALS AND METHODS: Five hundred consecutive, clinically diagnosed and untreated cases of pyoderma, attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from October 2010 to September 2011 were the subjects of this study. A detailed clinical examination, and relevant investigations including bacterial culture and sensitivity, were carried out and recorded. STATISTICAL ANALYSIS: For statistical analysis of data, the software 'EPI-INFO Version 6' was used, and Chi-square (chi(2)) test was applied. RESULTS: Of 19576 cases attending skin OPD during the study period, pyoderma was seen in 500 patients; the incidence being 2.55%. Males outnumbered females. The highest number of cases (109; 21.8%) was observed in 1st decade. Lower extremities were the commonest site of predilection. Primary pyodermas outnumbered secondary pyodermas. Furuncle (136; 27.2%) and infectious eczematoid dermatitis (62; 12.4%) were the commonest entities among primary and secondary pyoderma respectively. Staphylococcus aureus was the commonest causative agent in both primary and secondary pyoderma. It showed high susceptibility to amoxycillin + sulbactam, aminoglycosides and cefoperazone, moderate susceptibility to linezolid, while low susceptibility to fluoroquinolones and cephalexin. CONCLUSION: Such studies help to assess the changing trend of bacterial infections, their causative organisms and antibiotic susceptibility pattern. PMID- 26538697 TI - A Rare Case of Plantar Epithelioma Cuniculatum Arising from a Wart. AB - A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 * 7 cm on the left heel region associated with discharge of foul smelling cheesy material. There was also a enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. X-ray left ankle was done which showed some soft tissue swelling. A skin biopsy showed hyperkeratosis, acanthosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass pressing on the underlying dermis were seen. There was formation of multiple large keratin filled invaginations and crypts. No atypical cells were seen. Based on history, clinical examination and investigations, a diagnosis of epithelium cuniculatum type of verrucous squamous cell carcinoma was made. A wide excision with a flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum. PMID- 26538698 TI - Jellyfish Envenomation Presenting with Delayed Identical Cutaneous Lesions in a Mother and Child. AB - Jellyfish envenomation can present with local cutaneous lesions both immediate and delayed. While the immediate reaction is toxin mediated, an immune mechanism is responsible for the delayed eruptions. This is a report of a mother and child who developed identical papular lesions in a bizarre, linear distribution after coming in contact with jellyfish almost simultaneously while on holiday. Histology showed focal basal cell degeneration along with peri-vascular and peri appendageal lympho-mononuclear infiltrate. Both patients responded well to topical tacrolimus. PMID- 26538699 TI - X-linked Ichthyosis Presenting as Erythroderma: A Rare Case. AB - X-linked ichthyosis is a rare form of dermatological disease and when it presents as erythroderma it is even rarer. History of consanguineous marriage and prolonged labor during birth of patient, generalized scaling which gets better in summer months, flexural involvement, cryptorchidism made a diagnosis of X-linked ichthyosis. We report this case because of its rarity as erythroderma. PMID- 26538700 TI - Acne in Klinefelter Syndrome-46XY/47XXY Mosaicism? AB - Klinefelter syndrome (KFS) is the most common non-heritable sex chromosome anomaly caused by nondisjunction during cell division and contains two or more X chromosomes. More than two third of all cases are homogenous (47XXY) and the remaining are mosaic (46XY/47XXY). Lower limb ulcers are frequently observed and attributed to impaired fibrinolysis. A case of KFS with post acne scars and leg ulcers is presented. The rarity of acne in this syndrome is explained by the phenomenon of mosaicism. PMID- 26538701 TI - Solitary Neurofibroma at the Base of the Tongue: A Rare Presentation. AB - A 75-year-old man presented with a slowly growing mass at the right side of the base of the tongue for 4 months. The mass was painless initially but had become very painful during preceding 4 weeks. On examination a 3 cm diameter, oval swelling was observed at the right side of the base of the tongue. It was firm in consistency, slightly tender, non-ulcerative, and with irregular surface. A deep incisional biopsy was taken from mass under general anesthesia. Histopathology report identified the mass consistent with neurofibroma. It featured typical pallisading arrangement of fascicles of spindle-shaped cells and there was no evidence of malignancy. An absence of Verocay body and thick hyalinized vessels ruled out Schwannoma. No similar lesions were found in any other part of the patient's body. He exhibited no skin pigmentation, no hearing deficit, and no evidence suggestive of any systemic disorders that might have been attributable to the tongue base neurofibroma. His family history was also negative. Thus, a diagnosis of isolated neurofibroma of the tongue was established. The patient was advised excision of the mass but he refused and lost in follow up. PMID- 26538702 TI - Subcutaneous Zygomycosis: A Report of One Case Responding Excellently to Potassium Iodide. AB - Subcutaneous Zygomycosis is a rare opportunistic fungal infection caused by Basidiobolus ranarum. Though this entity is endemic in South India, limited numbers of cases have been reported from this part of the country. We report a case of subcutaneous zygomycosis in a 25 year old lady who presented with a nontender, firm to hard swelling over the upper-left arm. Finger was easily inserted below the indurated edge. Histopathology revealed suppurative granuloma with aseptate hyphae. Patient responded excellently to saturated solution of potassium iodide in subsequent visits. PMID- 26538703 TI - Colocalization of Lichen Planus Hypertrophicus and Epidermal Inclusion Cyst: An Incident Unreported Hitherto. AB - Colocalization of diseases in dermatology has always remained elusive and a puzzle, difficult to unscramble. Co-localization of two rare and disparate dermatoses has been reported on several occasions. Lichen planus (LP) has been described to colocalize with several dermatoses. We report here a case of LP hypertrophicus co-localizing with epidermoid cysts on the scrotum of a 35-year old man for the unusual site and association. PMID- 26538704 TI - Nodulo-ulcerative Tuberculosis of the Glans Penis-A Case Report and a Discussion on Nomenclature of Genital Tuberculosis. AB - Lupus vulgaris is a chronic paucibacillary form of cutaneous tuberculosis occurring in a person with a moderate to high degree of immunity. It commonly occurs over the buttocks and trunk in India. Involvement of the genitalia is uncommon, and lesions involving the penis, extremely rare with few cases reported worldwide. There also exists a confusion regarding nosology of tuberculosis of the genitalia. A brief discussion and review of literature are being discussed along with the report of a case of genital tuberculosis involving the glans penis. PMID- 26538705 TI - Spindle Cell Hemangioendothelioma: Rare Clinical Entity. AB - Spindle-cell hemangioendothelioma (SCHE) comprise a rare subset of vascular tumors, and here, we describe such a case and review the clinical presentation, patho-physiology, differential diagnosis of these tumors to promote early identification and discussion guidance. A 25-years-old male patient presented with multiple painful elevated swellings of both left upper and lower extremities for last 15 years without any systemic involvement. After excluding close differential diagnosis by relevant investigations an excisional biopsy was performed. Based on clinical, radiological and histopathological findings, diagnosis of SCHE was made and full thickness excision and skin grafting were performed. The case is reported due to its rarity and adds our knowledge to the existing literature. PMID- 26538706 TI - Comment on: Quality of Life and Psychological Morbidity in Vitiligo Patients: A Study in a Teaching Hospital from North-East India. PMID- 26538707 TI - Authors' Reply. PMID- 26538708 TI - Comment on: Quality of Life and Psychological Morbidity in Vitiligo Patients: A Study in a Teaching Hospital from North-East India. PMID- 26538709 TI - Authors' Reply. PMID- 26538710 TI - Comment on: "Epidemiological Study of Insect Bite Reactions from Central India". PMID- 26538711 TI - Authors' Reply. PMID- 26538712 TI - Asymptomatic Papular Eruption in a 60 Year Old Man. PMID- 26538713 TI - Erythromycin as a Safe and Effective Treatment Option for Erythema Annulare Centrifugum. AB - BACKGROUND: Erythema annulare centrifugum (EAC) is an inflammatory dermatosis with unknown etiology. It is usually self-limited, but chronic disease may be difficult to treat. We observed incidentally the therapeutic effect of erythromycin for EAC among patients taking erythromycin for other diseases. AIM: To evaluate the treatment response of erythromycin for EAC. MATERIALS AND METHODS: During the study period, from July 2007 to February 2011, all patients with EAC were assigned to erythromycin stearate tablet 1000 mg per day for two weeks. EAC was diagnosed by a constellation of clinical and pathological findings. The efficacy (before and after the treatment) was assessed clinically by one dermatologist and photographically by two blinded dermatologists. Secondary outcomes included adverse drug effects and recurrence. RESULTS: Eight patients were enrolled in this study. Most patients had chronic relapsing disease with poor response to previous treatment. All the patients showed rapid response with profound reduction in the size of lesion and erythema two weeks after initiation of erythromycin treatment. The response was so obvious and complete that a coincidental response was less likely. Three patients had recurrence of disease and they tended to have more extensive lesions. Readministration of erythromycin was effective. All patients tolerated the treatment well. CONCLUSION: Our study documented erythromycin as a safe and cost-effective treatment for EAC. PMID- 26538714 TI - Clinical Characteristics and Quality of Life of Seborrheic Dermatitis Patients in a Tropical Country. AB - BACKGROUND: Seborrheic dermatitis is a common chronic inflammatory skin condition that can have a negative impact on a patient's quality of life. Few studies have been conducted to assess the clinical characteristics of the disease and quality of life of the patients, especially in tropical countries. AIMS AND OBJECTIVES: The aim of this study was to demonstrate the clinical characteristics and quality of life of patients with seborrheic dermatitis in Thailand. MATERIALS AND METHODS: A cross-sectional study was performed at a university-based hospital and tertiary referral center in Bangkok, Thailand. The validated Thai version of the dermatology life quality index (DLQI) was used to evaluate patients' quality of life. RESULTS: A total of 166 participants were included. One hundred and forty seven patients (88.6%) experienced multiple episodes of the eruption. The mean of outbreaks was 7.8 times per years, ranging from once every 4 years to weekly eruption. The most common factor reported to aggravate seborrheic dermatitis was seasonality (34.9%), especially hot climate. The mean (SD) of the total DLQI score was 8.1 (6.0) with a range of 0 to 27. There was no statistically significant difference between the two DLQI categories regarding duration of disease, extent of involvement, symptoms or course of the disease. CONCLUSION: Although mild and asymptomatic, seborrheic dermatitis can have a great impact on the quality of life. Youth, female gender, and scalp lesions were significantly associated with higher DLQI scores. PMID- 26538715 TI - Acral Vitiligo and Lichen Sclerosus - Association or a Distinct Pattern?: A Clinical and Histopathological Review of 15 Cases. AB - BACKGROUND: Acral or acrofacial vitiligo (AFV) with bilateral lesions over the extremities and face is considered as a transitional form that may progress to generalized vitiligo. Oral and genital mucosal lesions are often integral to this pattern. Lichen sclerosus (LS) in a milder expression, results in oral and genital vitiligoid depigmentation without textural changes and thus needs to be differentiated from AFV. MATERIALS AND METHODS: We reviewed 217 cases of AFV recorded over a period of 12 years. RESULTS: One hundred and sixteen cases had associated oral/genital lesions. Among these, 15 patients demonstrated typical clinical as well as histological features of LS. DISCUSSION: Coexistence of typical LS essentially among oral and genital lesions of acral vitiligo suggests that acral vitiligo might be a distinct sub-group of NSV. Since both the diseases have an autoimmune basis, the co-existence may be explained by epitope spreading, as a result of interface dermatitis seen in vitiligo. In addition, the possibility of a common genetic predisposition needs to be explored. PMID- 26538716 TI - Atopic Dermatitis: A Cross-Sectional (Descriptive) Study of 100 Cases. AB - BACKGROUND: Atopic dermatitis is a distinct age-related clinical entity. Its etiopathogenesis is largely insubstantial. Nevertheless, it seems to be an outcome of interplay of maternal and inheritance, pregnancy/intrauterine and environmental factors. Besides, immune dysregulation, and nutritional supplements also play essential roles. Its diagnosis has been perpetuated by three or more major/minor criteria. OBJECTIVES: An endeavor to study its demographic and clinical pattern in contemporary prospective. MATERIALS AND METHODS: 100 fresh patients of atopic dermatitis, diagnosed on the basis of an established three or more major and minor criteria, salient presentations of which were recorded in a preset proforma, which also recorded age, duration, age of onset, and sex. Serum immunoglobulin E (IgE) levels were determined by conventional technique. The data thus obtained was analysed to study its clinical pattern and to correlate its severity to IgE levels. RESULTS: Its overall (new and old) prevalence was 0.98%, while that of new patients was 0.24%. 83 (83%) were in the age group of 2-12 years, of which 54 (83.1%) were males and 29 (82.9%) were female, of which 70 (70%) had urban, while 30 (30%) had rural background. Its duration varied from 8 to 192 weeks, with a mean of 76 weeks, and a standard deviation of 21.42 weeks [76 +/- 21.42]. CONCLUSION: Atopic dermatitis is a discrete, overt, age and IgE related entity frequently displaying varying demographic and clinical connotation. PMID- 26538717 TI - Clinico-epidemiological Study and Quality of Life Assessment in Melasma. AB - BACKGROUND: Melasma is one of the most common and distressing pigmentary disorders presenting to dermatology clinics. The precise cause of melasma remains unknown. It is notably difficult to treat and has a tendency to relapse. Its population prevalence varies according to ethnic composition, skin phototype, and intensity of sun exposure. Due to its frequent facial involvement, the disease has an impact on the quality of life of patients. AIMS: To study the clinico epidemiological pattern, dermascopy, wood's lamp findings and the quality of life in patients with melasma. SETTINGS AND DESIGN: Observational/descriptive study. MATERIALS AND METHODS: Patients with melasma were screened. History, clinical examination, Wood's lamp examination (WLE) and dermoscopy were done. Severity of melasma was assessed by the calculating melasma area severity index (MASI) score. Quality of Life (QOL) was assessed using MELASQOL scale with a standard structured questionnaire. STATISTICAL ANALYSIS: Descriptive, Chi-square test and contingency coefficient analysis. RESULTS: In 140 cases of melasma, 95 (67.9%) were females and 45 (32%) were males. Common age group affected was 31-40 years (65%). Majority were unskilled workers with average sun exposure of more than 4 hours (44%). Family history was observed in 18% cases. Malar type (68%) was the most common pattern observed. Mean MASI score was 5.7. WLE showed dermal type in 69% cases. Common findings on dermoscopy were reticular pigment network with perifollicular sparing and color varying from light to dark brown. Mean MELASQOL score was 28.28, with most patients reporting embarrassment and frustration. CONCLUSIONS: This study showed that melasma has a significant negative effect on QOL because though asymptomatic it is disfiguring affecting self-esteem. Dermoscopic examination did not help in differentiating the type of melasma. PMID- 26538718 TI - Safety and Efficacy of Growth Factor Concentrate in the Treatment of Nasolabial Fold Correction: Split Face Pilot Study. AB - BACKGROUND: Growth factors have long been known as an effective treatment for facial wrinkles. We developed growth factor concentrate (GFC) from the platelets and evaluated their clinical outcome in nasolabial folds. AIMS AND OBJECTIVES: We evaluated safety and efficacy of autologous GFC on patients with nasolabial folds. MATERIALS AND METHODS: Study was conducted on 80 patients for nasolabial folds in two groups. Group I (20) received bilateral single injection of GFC and group II (60) received single injection of GFC on the right side of the face and platelet-rich plasma (PRP) on the left side of the face. Severity of nasolabial folds was determined at the baseline and 3 months of follow-up visits based on wrinkle severity rating scale (WSRS), Global aesthetic improvement scale (GAIS) and atlas photographic grading at rest and at full smile. Objective clinical assessment and subjective satisfaction scale was determined for overall improvement at the end of the study. RESULTS: In group I, 2 subjects showed improvement after GFC treatment with the score of 3.1-4 (76-100%), 3 subjects with the score of 2.1-3 (51-75%), 14 with the score of 1.1-2 (26-50%) and 1 subject with the score of 0-1 (<25%) at the end of study. In group II, 51 subjects were evaluated at the end of study where, 34 (66%) showed superior improvements after GFC, 6 (11%) patients showed similar improvement on both side of the face, 10 (19.6%) patients showed no noticeable improvement on the either side of the face and only 1 patient (1.96%) showed superior improvement for PRP at the end of the study. Overall improvement score analysis showed that GFC was significantly superior to PRP (P < 0.001). CONCLUSION: Present study is a strong evidence to support the use of GFC for nasolabial folds. The results showed that the single application of GFC is highly effective and safe. PMID- 26538719 TI - Oral Tranexamic Acid with Fluocinolone-Based Triple Combination Cream Versus Fluocinolone-Based Triple Combination Cream Alone in Melasma: An Open Labeled Randomized Comparative Trial. AB - BACKGROUND: Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy. Tranexamic acid, a plasmin inhibitor, has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results. OBJECTIVES: To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in melasma among Indian patients. MATERIALS AND METHODS: 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study. Participants were randomly divided into two groups with 20 patients in each group. Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05%, and hydroquinone 2% once daily for 8 weeks. Response was evaluated using melasma area severity index (MASI) at baseline, 4 weeks, and 8 weeks. RESULTS: 40 patients completed the study. The MASI scores at baseline, 4 weeks and 8 weeks in group A were 15.425 + 1.09, 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05, 6.135 + 4.94 and 2.19 + 3.38. Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks (P value 0.014) and 8 weeks (P value 0.000). The efficacy was maintained throughout the 6-month follow-up period. CONCLUSION: Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma. PMID- 26538720 TI - Pattern of Childhood Onset Vitiligo at a Tertiary Care Centre in South- West Rajasthan. AB - CONTEXT: Onset of vitiligo during childhood is not uncommon but the data is limited on this subject. AIMS: This study was planned to assess the magnitude of childhood onset vitiligo (COV) and adulthood onset vitiligo (AOV), and compare their clinical pattern. SETTINGS AND DESIGN: A cross sectional hospital based clinical study. MATERIALS AND METHODS: Consecutive patients with vitiligo attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from April 2012 to September 2012 were the subjects of this study. A detailed history taking followed by general, systemic and cutaneous examination, and relevant investigations were carried out. The findings were recorded in a proforma for analysis and interpretation of data. STATISTICAL ANALYSIS USED: Statistical analysis of data was done using chi- square and Z test. RESULTS: Of the 295 patients seen during the study period, 109 (36.95%) were patients with COV while 186 (63.05%) had AOV; the COV: AOV ratio being 1: 1.71. Amongst COV patients, females (65/109; 59.63%) outnumbered males (44/109; 40.37%). Maximum (51; 46.79%) patients of COV had onset of their disease on head and neck, out of which eyelid was the initial site of lesion in 29 (26.61%) patients. None of COV patients had universal and isolated mucosal vitiligo. CONCLUSIONS: Female predominance, affection of eyelids as initial site, and less frequent mucosal involvement in COV were the clinical features different from AOV. PMID- 26538721 TI - Alitretinoin in Dermatology-An Update. AB - Alitretinoin is a pan retinoic acid agonist. It was initially used as 0.1% gel in the management of localized Kaposi's sarcoma. At present, the use of systemic alitretinoin has proved extremely efficacious in the management of recalcitrant chronic hand eczema. Furthermore, there have been other retinoid responsive dermatosis that have demonstrated remission post usage of systemic alitretinoin. With a better toxicity profile, compared to the other systemic retinoids, alitretinoin could be considered a valuable treatment option in the near future for the treatment of these dermatologic disorders. PMID- 26538722 TI - Argyria after Silver Nitrate Intake: Case Report and Brief Review of Literature. AB - Argyria is a condition characterized by pigmentary changes secondary to exposure to silver salts and its accumulation in skin, mucous membranes and annexes, which typically produces blue or gray-blue spots. A case of a male patient 62 years old, previously healthy, who has a blue-gray hyperpigmentation on the face, trunk and upper extremity, affecting sun-exposed areas is presented. He admitted having ingested silver nitrate for 5 years at a rate of 1 bottle per week, with the intent to kill microorganisms in his body. PMID- 26538723 TI - Violaceous Maculopapular Rash in a Newborn: Congenital Rubella Syndrome. AB - Congenital rubella syndrome involves a configuration of systemic and cutaneous manifestations in a neonate due to in utero infection caused by the rubella virus. The case of a preterm neonate with blueberry muffin lesions and classical as well as rare systemic features of congenital rubella syndrome is reported. PMID- 26538724 TI - Giant Angioleiomyoma of Knee Presenting as Painless Ulcer: The First Case Report. AB - Angioleiomyomas are benign tumors originating in the vascular smooth muscle. The tumor typically presents as painful, solitary, small (<2 cm), slow growing, subcutaneous nodule. Angioleiomyoma of the knee is rare, and only few cases have been reported so far. We have described herein a giant angioleiomyoma of the knee presenting as a painless ulcer in a 22-year-old man. There was no intra-articular extension of the tumor, and total excision was curative. This is the first case report of giant angioleiomyoma of the knee as well as the first case report of angioleiomyoma presenting as a painless ulcerative lesion. PMID- 26538725 TI - Eosinophilic Pustular Folliculitis Post Chemotherapy in a Patient of Non-Hogkins Lymphoma: A Case Report. AB - Eosinophilic pustular folliculitis (EPF) was originally described by Ofuji in Japanese patients without any systemic disease. Later it was widely associated with HIV. Lately a large number of hematological malignancies have been associated with EPF. We hereby report an association of non-Hogkins lymphoma with EPF, probably the first in Indian context. PMID- 26538726 TI - Autoantibodies Against Multiple Epitopes in Bp180 and Laminin Gamma-1 in Subepidermal Blistering Skin Disease Associated with Psoriatic Erythroderma. AB - We report a 79-year-old Japanese man who developed subepidermal blistering skin disease after an 8-year history of psoriasis. Histology of a bullous lesion revealed a subepidermal blister with a mixed inflammatory cell infiltrate and fibrin nets. Indirect immunofluorescence using normal human skin sections revealed IgG and IgA autoantibodies in the patient serum, which bound to the epidermal side of 1M NaCl-split skin sections. Immunoblot analysis revealed that both IgA and IgG antibodies reacted with the BP180 NC16a domain and the 120-kDa LAD-1 and that IgG antibodies also reacted with the BP180 C-terminal domain and laminin gamma-1. These findings indicated that autoantibodies to laminin gamma-1 and multiple epitopes in BP180 ectodomain played a role in the pathogenesis of this unique autoimmune subepidermal blistering skin disease associated with psoriasis. PMID- 26538727 TI - The Diagnostic Dilemma of Cutis Laxa: A Report of Two Cases with Genotypic Dissimilarity. AB - Cutis laxa is a heterogeneous group of diseases, with loose, wrinkled skin folds and hyperelasticity of the skin. There are overlapping of clinical features of the group of syndrome associated with cutis laxa, including congenital cutis laxa, wrinkly skin syndrome and gerodermia osteodysplastica. All these conditions present a challenge to the clinician. Thus, molecular diagnosis is the only way to resolve these phenotypically similar conditions. We hereby describe two Indian patients with wrinkled skin and mild craniofacial dysmorphic features who had molecular confirmation of autosomal recessive cutis laxa. PMID- 26538728 TI - Asymptomatic Papulo-nodules Localized to One Finger. AB - Subcutaneous or deep granuloma annulare is a benign asymptomatic condition characterized by firm asymptomatic nodules in deep subcutaneous tissues that may be associated with intradermal lesions. A 53-year-old female presented with asymptomatic skin-colored, firm nodules over the right ring finger. Histopathology revealed a palisading granuloma with central degenerated collagen and mucin deposition in the dermis suggestive of granuloma annulare. Isolated and unilateral involvement of a single digit with clusters of nodules of subcutaneous granuloma annulare (GA) in an adult is rare and differentiation from its simulator rheumatoid nodule is essential. PMID- 26538729 TI - Cutaneous Larva Migrans in Early Infancy. AB - Cutaneous larva migrans or creeping eruptions is a cutaneous dermatosis caused by hookworm larvae, Ancylostoma braziliense. A 2-month-old female child presented with a progressive rash over the left buttock of 4 days duration. Cutaneous examination showed an urticarial papule progressing to erythematous, tortuous, thread-like tract extending a few centimeters from papule over the left gluteal region. A clinical diagnosis of cutaneous larva migrans was considered. Treatment with albendazole led to complete resolution, confirming the diagnosis. This is to the best of our knowledge, the youngest age at which this condition is being reported. PMID- 26538730 TI - Phenytoin Induced Cutaneous B Cell Pseudolymphoma. AB - Cutaneous pseudolymphomas are benign lymphoproliferative processes mimicking lymphomas clinically and histologically. One of the precipitating factors for pseudolymphoma is drugs like anticonvulsants, antidepressants and angiotensin converting enzyme inhibitors. According to existing literature phenytoin-induced cutaneous pseudolymphomas are usually T-cell predominant. Most often withdrawal of the drug with or without short-course systemic steroids can attain a cure. Rarely malignant transformation has been reported years later despite withdrawal of the offending drug, which necessitates a long-term follow up of the affected. We report an 80-year-old male patient who was receiving phenytoin sodium and who presented with diffuse erythema and infiltrated skin lesions which histologically resembled cutaneous B-cell lymphoma. Substituting phenytoin with levetiracetam achieved resolution of symptoms. Further evaluation was suggestive of a reactive process. A detailed drug history is of paramount importance in differentiating drug-induced pseudolymphoma from lymphoma. Searching literature we could not find any previous reports of phenytoin-induced cutaneous B-cell pseudolymphoma. PMID- 26538731 TI - A Sporadic Case of Ichthyosis Curth Macklin: Rare Presentation of a Rare Disease. AB - Ichthyosis hystrix is a rare autosomal dominant genodermatosis, characterized by persistent spiny hyperkeratotic scales which cover a significant part of the skin surface. Based on the pattern of distribution, five clinical variants namely Brocq type, Lambert type, Curth-Macklin type, Rheydt type and Bdeltafverstedt type have been described. We report the case of an 11-year-old male child with spiny, hyperkeratotic scales all over the body since birth with sparing of scalp and central part of the face. Palmoplantar keratoderma was also present. These clinical features are suggestive of Ichthyosis Curth Macklin, which has been typically described in families. However, family history was negative in our patient. The case is being reported on account of rarity of the disease, that too with a very rare sporadic presentation. PMID- 26538732 TI - Zosteriform Lesions in an Elderly Man-Look Beyond Herpes Zoster. AB - Cutaneous metastasis in a zosteriform pattern is a very rare entity being reported only in 63 patients worldwide. Cutaneous metastases usually presents late in the course of the disease or sometimes after the treatment of the primary when it indicates recurrence of a treated malignancy. We report a case of zosteriform cutaneous metastases masquerading as lymphangioma without prior presentation of the primary malignancy. PMID- 26538733 TI - Bilateral Symmetrical Congenital Giant Becker's Nevus: A Rare Presentation. AB - Becker's nevus is a focal epidermal hypermelanotic disorder. It morphologically presents as unilateral, hyperpigmented, hypertrichotic patch on upper trunk, proximal upper extremities and arms. However, Becker's nevus presenting as bilateral, symmetrical patches is rare. Herein, we report a rare case of giant Becker's nevus with bilateral symmetrical presentation in an adult male. PMID- 26538734 TI - Ram's Horn Nail - Giant Onychomatricoma Treated by Complete Surgical Excision- A Rare Case Report. AB - Giant onychomatricoma is a rare fibroepithelial nail matrix tumor with only two previous reports in literature, from Mexico. An 80-year-old female patient presented with a progressively painless mass in the left great toe nail, following trauma, of 2 years duration. On examination there was a single, hard, immobile mass of size 4 * 3 * 2 cm with proximal hyperpigmentation of the left great toe nail. The mass was totally excised and a punch biopsy of nail matrix was taken. Histopathology revealed hyperkeratosis, acanthosis, multiple channels lined by flattened epithelium and fibrocollagenous tissue in horizontal orientation in deeper layers. The patient had no recurrence after 1 month. We report this case for its rare and distinct clinical presentation, characteristic histopathology and easy surgical treatment. PMID- 26538735 TI - Chronic Myeloid Leukemia Arising in a Patient of Neurofibromatosis Type 1. AB - Neurofibromatosis type 1 (NF1) represents a major risk factor for development of malignancies, particularly malignant peripheral nerve sheath tumors (MPNST), optic gliomas, other gliomas, and leukemia. We report an unusual case of chronic myeloid leukemia (CML), developed in a patient of NF1. A 40-year-old Indian male, clinically manifesting NF1 since his childhood, presented with huge splenomegaly. Patient also had a large tumor mass arising in a cafe-au-lait spot on lower back with rapid growth in last 6 months. Excision of this tumor was done, and it turned out to be a diffuse neurofibroma histologically. Peripheral smear was also done in view of splenomegaly, which showed features of chronic myeloid leukemia. CML rarely co-exists with NF1, and there are a very few reports of such cases. It is important to be aware of the possibility that not only the malignant change in benign PNST is more common in these patients, but also other malignancies like CNS tumors and hematolymphoid neoplasm do occur with increased frequency. PMID- 26538736 TI - Bacillary Angiomatosis in Immunocompetent Patient with Atypical Manifestations. AB - Bacillary angiomatosis is an infectious disease caused by two Gram-negative bacilli; this disease usually affects immunosuppressed hosts with a history of cat scratch. We report a rare case of bacillary angiomatosis in an immunocompetent 26-year-old woman with no history of exposure to cats, and with atypical clinical features (very pruritic vascular papules and nodules with ulceration and hemorrhage on the right arm and fingers). She was successfully treated with clarithromycin for 3 months. Bacillary angiomatosis must be kept in mind in the differential diagnosis of any papules and nodules in cases of unknown etiology and also in immunocompetent patients and HIV-negative individual. PMID- 26538737 TI - Lichen Planus-like Keratosis: Another Differential Diagnosis for Kaposi Sarcoma. AB - Epidemic Kaposi sarcoma is a common finding among HIV/AIDS patients that are not under antiretroviral treatment, and sometimes it is the first sign of the disease. However, it can be seen even in patients with undetectable viral load and high CD 4 cell count. Under these circumstances, the clinical presentation can be atypical in location or number. For this reason, the number of differential diagnosis is increased and biopsy of the suspicious lesions is essential for an accurate diagnosis and further apropiate treatment. PMID- 26538738 TI - An Unusual Clinical Presentation of Eccrine Poroma Occurring on the Auricle. AB - Eccrine poromas are benign, slow-growing, solitary tumors originating from the intraepidermal portion of eccrine sweat ducts. Approximately 65% of these tumors occur on the soles of the feet, while 10% occur on the hands where a high concentration of eccrine sweat glands exists. Less frequently it occurs in other sites such as neck, chest, forehead, nose, and scalp with sporadic occurrences. A 43-year-old Korean female presented with a mass on her right auricle, which had been present for 5 years. The mass increased gradually in size with pain, oozing, and bleeding. A biopsy of the mass revealed monomorphic basaloid cells, which may extend into the underlying dermis, in a richly vascularized stroma, with a variable number of cystic or ductal structures. The patient was diagnosed as having eccrine poroma. In this case, the eccrine poroma showed unusual clinical presentation. PMID- 26538739 TI - Imatinib-induced Extensive Hyperpigmentation in a Case of Chronic Myeloid Leukemia. AB - Imatinib, a tyrosine kinase inhibitor, is well known to cause hypopigmentation because of its inhibitory effect on melanocytes. Herewith we report a case of chronic myeloid leukemia who developed extensive hyperpigmentation following imatinib therapy. PMID- 26538740 TI - Mal de Meleda with Congenital Cataract: A Novel Case Report. AB - Mal de meleda (MdM), a rare autosomal recessive genodermatosis is characterized by erythema and hyperkeratosis of the palms and soles with a sharp demarcation and that progress with age (progrediens) and extend to the dorsal aspects of the hands and feet (transgrediens). It has been associated with various conditions albeit rarely with congenial cataract. Ocular lens and the skin have the same embryological origins. We hereby present this novel case report of Mal de meleda in association with congenital posterior subcapsular cataract which to the best of our knowledge has not been reported from India before. PMID- 26538741 TI - Livedoid Vasculopathy with Hyperhomocysteinemia Responding to Hyperbaric Oxygen Therapy. AB - A 30-year-old male presented to the dermatology department with complaints of multiple ulcers over both legs of 6 years duration. The ulcers had a waxing and waning course with present exacerbation of lesions since 1 month. Dermatological examination revealed multiple ulcers distributed in a reticular pattern over medial and lateral aspects of both lower legs, extensor aspect of both ankles and dorsum of both feet. Multiple interspersed atrophic porcelain white scars were also present. Investigations revealed raised serum homocysteine levels. A skin biopsy from the ulcers showed features of livedoid vasculopathy. Following recurrence of lesions after oral corticosteroid therapy, the patient was given a course of hyperbaric oxygen therapy for the ulcers to which he responded very well. This case is being presented for the novel option of hyperbaric oxygen therapy in livedoid vasculopathy, which by itself is rarely reported in this part of the world. PMID- 26538742 TI - Woolly Hair with Systematized Epidermal Nevus. AB - Woolly hair is a hair shaft disorder characterized by fine and tightly curled hair. Woolly hair could be syndromic (associated with systemic disease) or non syndromic (not associated with any systemic disease). Woolly hair is described in association with many skin, dental, ophthalmic and cardiac anomalies but association of woolly hair with bilateral systematized epidermal nevus described in our case is first of its kind. PMID- 26538743 TI - Chediak-Higashi Syndrome: A Case Series from Karnataka, India. AB - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease, characterized by partial oculocutaneous albinism, frequent pyogenic infections, and the presence of abnormal large granules in leukocytes and other granulecontaining cells. The abnormal granules are readily seen in blood and marrow granulocytes. Other clinical features include silvery hair, photophobia, nystagmus and hepatosplenomegaly. However, the presence of abnormal giant intracytoplasmic granules in neutrophils and their precursors are diagnostic of CHS. Here, we present a series of five cases, out of which four presented in the accelerated phase. In all the five cases, the giant granules were noted predominantly in the cytoplasm of lymphocytes, which is a rare occurrence compared to those present in the granulocytes. PMID- 26538744 TI - Jadassohn Lewandowsky Syndrome: A Rare Entity. AB - Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis characterized by hyperkeratosis affecting the nails and palmoplantar areas, oral leucokeratosis, and cystic lesions. It is classically subdivided into two major variants, PC-1 (Jadassohn-Lewandowski syndrome) and PC-2 (Jackson-Lawler syndrome), according to the localization of the mutations in the KRT6A/KRT16 or KRT6B/KRT17 genes, respectively. We report a 9-year-old male patient with a history of thickened, discolored nails, raised spiny skin lesions all over the body since birth with focal plantar keratoderma and absence of natal teeth. PMID- 26538745 TI - Coexistence of Solid (Nodular) and Differentiated (Adenoid) Basal Cell Carcinoma at the Same Anatomical Site. AB - Coexistence of two different histopathological types of basal cell carcinomas (BCCs) in the same anatomical site is rare and interesting. Herein, we report a case of coexistence of nodular and adenoid BCC in a 78-year-old peasant who presented with a plaque and a globular swelling on left paranasal region of few years duration. Histopathology of skin biopsy with immunohistochemistry study using antibodies to S100, epithelial membrane antigen (EMA) and cytokeratin 7 (CK 7) from the margin of the ulcer and globular swelling confirmed the diagnosis that revealed features of nodular and adenoid basal cell carcinoma, respectively. Investigative work up did not reveal evidence of metastasis. PMID- 26538746 TI - De Novo Histoid Leprosy. AB - Histoid leprosy is an uncommon entity with specific clinical, histopathological and bacteriological features. Histoid lepromas are sudden eruption of dome shaped lesions usually associated with dapsone resistance, as a variant of lepromatous leprosy or rarely arising de novo. We report a case who presented for the first time with histoid features with no history of taking dapsone/antileprosy treatment earlier in an elderly male with small to large lesions over normal skin in the post-leprosy elimination era. PMID- 26538747 TI - Lichenoid Variant of Chronic Cutaneous Graft Versus Host Reaction Post Blood Transfusion: A Rare Event Post Blood Transfusion. AB - Chronic graft versus host disease (GVHD) is a less frequently seen disease that occurs post solid organ or bone marrow transplantation. Chronic GVHD occurring post blood transfusion is an even more uncommon disease. It can present either as a lichenoid disease or as a sclerodermatous disease involving multiple systems. In this article, we report a case of chronic graft versus host reaction occurring in skin secondary to blood transfusion. PMID- 26538748 TI - Vulval Swelling: A Diagnostic Dilemma. AB - Vulval swellings have always caused dilemmas in diagnosis and more so when they are huge in size. Sebaceous cysts are known to occur as a result of blocked pilo sebaceous gland and duct or as a result of any injury to the skin. Face, neck, chest, back, scalp, and ears are known sites, however, they also occur over private parts. They are mostly asymptomatic but cause intense pain and discomfort if infected. Symptomatic cysts warrant removal. PMID- 26538749 TI - Biopsychosocial Factors Associated with Prurigo Nodularis in Endogenous Eczema. AB - BACKGROUND: Prurigo nodularis is a dermatological manifestation secondary to chronic scratching or picking on focal areas of the skin. Its pathogenesis remains poorly understood, and limited data has indicated its association with psychological factors. AIM: To determine the biological, psychological and social factors associated with the occurrence of prurigo nodularis in patients with underlying endogenous eczema. METHODS: A prospective case-control questionnaire based study on patients with endogenous eczema, with and without prurigo nodules, was performed. The Impact of Skin Disease on Daily Life questionnaire was used to assess dimensions of physical functioning, including extent and severity of skin disease, itch, pain, fatigue and scratching, as well as dimensions of psychological and social functioning, including mood, illness cognition, disease related impact, stigmatization and social support. RESULTS: Thirty-six cases and 47 controls were recruited. Patients with endogenous eczema and prurigo nodules indicated a higher itch score on the visual analog scale over the previous 4 weeks compared to those without prurigo nodules (p=0.0292). There were no significant differences between the 2 groups in the scores reflecting the other parameters of physical, psychological and social functioning. CONCLUSION: In patients with endogenous eczema, those with prurigo nodules experience a greater itch intensity compared to those without prurigo nodules. There were no other physical, psychological and social factors that were found to be associated with the occurrence of prurigo nodules in endogenous eczema. PMID- 26538750 TI - Erythema Dyschromicum Perstans: Response to Topical Tacrolimus. AB - BACKGROUND: Erythema dyschromicum perstans, a rare dermatosis of obscure etiopathogenesis and significant cosmetic morbidity, have no satisfactory treatment. OBSERVATIONS: Two patients with having characteristic asymptomatic and slowly progressive, slate-grey macular lesions with distinct red borders involving the face, neck, upper trunk and limbs were diagnosed clinicopathologically as erythema dyschromicum perstans. Both were treated successfully with topical tacrolimus 0.1% ointment. CONCLUSIONS: Overall, response to several therapeutic modalities including clofazimine and dapsone therapy is said to vary from complete failure to variable or inconsistent. Topical tarolimus provides an effective and safe alternative therapeutic option in erythema dyschromicum perstans. PMID- 26538751 TI - Usefulness of MRI in Delineation of Dermal and Subcutaneous Verrucous Hemangioma. AB - Magnetic resonance imaging (MRI) has established itself as diagnostic modality of choice of soft tissue and musculoskeletal lesions but dermatological lesions have been diagnosed mainly by clinical examination. We present MRI features of dermal and subcutaneous verrucous hemangioma involving the dorsum of foot in a 20-year old male and its usefulness in differentiating it from angiokeratoma with similar clinical features. PMID- 26538752 TI - What is Masquerading as a cyst. PMID- 26538753 TI - Proximal tibiofibular joint: Rendezvous with a forgotten articulation. AB - The proximal tibiofibular joint (PTFJ) is a plane type synovial joint. The primary function of the PTFJ is dissipation of torsional stresses applied at the ankle and the lateral tibial bending moments besides a very significant tensile, rather than compressive weight bearing. Though rare, early diagnosis and treatment of the PTFJ dislocation are essential to prevent chronic joint instability and extensive surgical intervention to restore normal PTFJ biomechanics, ankle and knee function, especially in athletes prone to such injuries. PTFJ dislocations often remain undiagnosed in polytrauma scenario with ipsilateral tibial fracture due to the absence of specific signs and symptoms of PTFJ injury. Standard orthopedic textbooks generally describe no specific tests or radiological signs for assessment of the integrity of this joint. The aim of this paper was to review the relevant clinical anatomy, biomechanics and traumatic pathology of PTFJ with its effect on the knee emphasizing the importance of early diagnosis through a high index of suspicion. Dislocation of the joint may have serious implications for the knee joint stability since fibular collateral ligament and posterolateral ligament complex is attached to the upper end of the fibula. Any high energy knee injury with peroneal nerve palsy should immediately raise the suspicion of PTFJ dislocation especially if the mechanism of injury involved knee twisting in flexion beyond 80 degrees and in such cases a comparative radiograph of the contralateral side should be performed. Wider clinical awareness can avoid both embarrassingly extensive surgeries due to diagnostic delays or unnecessary overtreatment due to misinformation on the part of the treating surgeon. PMID- 26538754 TI - Surgical hip dislocation for treatment of cam femoroacetabular impingement. AB - BACKGROUND: Cam femoroacetabular impingement is caused by a misshapen femoral head with a reduced head neck offset, commonly in the anterolateral quadrant. Friction in flexion, adduction and internal rotation causes limitation of the hip movements and pain progressively leading to labral and chondral damage and osteoarthritis. Surgical hip dislocation described by Ganz permits full exposure of the hip without damaging its blood supply. An osteochondroplasty removes the bump at the femoral head neck junction to recreate the offset for impingement free movement. MATERIALS AND METHODS: Sixteen patients underwent surgery with surgical hip dislocation for the treatment of cam femoroacetabular impingement by open osteochondroplasty over last 6 years. Eight patients suffered from sequelae of avascular necrosis (AVN). Three had a painful dysplastic hip. Two had sequelae of Perthes disease. Three had combined cam and pincer impingement caused by retroversion of acetabulum. All patients were operated by the trochanteric flip osteotomy with attachments of gluteus medius and vastus lateralis, dissection was between the piriformis and gluteus minimus preserving the external rotators. Z shaped capsular incision and dislocation of the hip was done in external rotation. Three cases also had subtrochanteric osteotomy. Two cases of AVN also had an intraarticular femoral head reshaping osteotomy. RESULTS: Goals of treatment were achieved in all patients. No AVN was detected after a 6 month followup. There were no trochanteric nonunions. Hip range of motion improved in all and Harris hip score improved significantly in 15 of 16 cases. Mean alpha angle reduced from 86.13 degrees (range 66 degrees -108 degrees ) to 46.35 degrees (range 39 degrees -58 degrees ). CONCLUSION: Cam femoroacetabular Impingement causing pain and limitation of hip movements was treated by open osteochondroplasty after surgical hip dislocation. This reduced pain, improved hip motion and gave good to excellent results in the short term. PMID- 26538755 TI - Proximal tibial fractures with impending compartment syndrome managed by fasciotomy and internal fixation: A retrospective analysis of 15 cases. AB - BACKGROUND: Proximal tibia fractures with compartment syndrome present a challenge for orthopedic surgeons. More often than not these patients are subjected to multiple surgeries and are complicated by infection osteomyelitis and poor rehabilitation. There is no consensus in the management of these fractures. Most common mode is to do early fasciotomy with external fixation, followed by second stage definitive fixation. We performed a retrospective study of proximal tibia fractures with impending compartment syndrome treated by single stage fasciotomy and internal fixation. Results in terms of early fracture union, minimum complications and early patient mobilization were very good. MATERIALS AND METHODS: Fifteen patients who were operated between July 2011 and June 2012 were selected for the study. All documents from their admission until the last followup in December 2013 were reviewed, data regarding complications collected and results were evaluated using Oxford Knee scoring system. RESULTS: At the final outcome, there was anatomical or near anatomical alignment with no postoperative problems with range of motion of near complete flexion (>120) in all patients within 3 months. 13 patients started full weight bearing walking at 3 months. Delayed union in two patients and skin necrosis in one patient was observed. CONCLUSIONS: Since the results are encouraging and the rehabilitation time is much less when compared to conventional approaches, it is recommended using this protocol to perform early fasciotomy with the definitive internal fixation as single stage surgery to obtain excellent followup results and to reduce rehabilitation time, secondary trauma, expense of treatment and infection rate. PMID- 26538756 TI - Arthroscopic repair of the meniscal injury using meniscal repair device. AB - BACKGROUND: Total meniscus resection after meniscus tear usually leads to faster degeneration and osteoarthritis of the knee joint. Preservation and repair of the injured menisci are therefore of great clinical importance. The aim of this study was to evaluate the clinical effects of arthroscopic repair of meniscal injuries using the Fast-Fix device. MATERIALS AND METHODS: 96 patients (58 males, 38 females) with mean age of 24.3 years (range 12-46 years)) with a meniscus injury were treated with the Fast-Fix device under arthroscopy between July 2007 and June 2009. The right and left knees were involved in 46 and 50 patients respectively. In 12, 46 and 38 patients, the injury was located in the anterior horn, body and posterior horn respectively. In 38, 45 and 13 patients, it was in the red, red-white, and white regions, respectively. All-inside and outside-in techniques were used for these meniscal injuries. Criteria for successful surgery were no locking pain or swelling and a negative McMurray test. RESULTS: The mean followup period was 3.7 years (range 2-5 years). The surgical success rate was 91.7% (n = 88). The mean Lysholm score increased from 47.8 +/- 10.4 preoperatively to 85.7 +/- 12.8 postoperatively. The mean Tegner activity score was 7.4 +/- 1.6 (range 5-9) preinjury, 2.1 +/- 0.9 (range 0-4) preoperatively and 7.2 +/- 2.2 (range 4-10) postoperatively (P < 0.001). A total of 92 patients (95.8%) returned to full-time work. The International Knee Documentation Committee score increased from 32.7 +/- 10.7 (range 10.3-51.7) preoperatively to 82.5 +/- 5.1 (range 65.1-91.2) postoperatively (P < 0.001). CONCLUSIONS: The Fast Fix system is an efficient, safe and effective suture technique for meniscal repair. PMID- 26538757 TI - Reconstruction by bone transport after resection of benign tumors of tibia: A retrospective study of 38 patients. AB - BACKGROUND: The commonly used reconstructive options after post resection defects in bone tumors like megaprosthesis, autograft, allograft, bone graft substitutes and recycled bone have their own demerits on a long term. Bone transport that regenerates patient's own bone is a less explored option of reconstruction after resection of benign bone tumors and reports on this are limited. This technique is very much relevant in tibia where Ilizarov fixator is surgeon and patient friendly. We report our experience. MATERIALS AND METHODS: This is a retrospective series of resection and bone transport in 38 patients with benign tumor of tibia. There were 14 males and 24 females with mean age of 23.40 years (range 9-40 years). Lesion was located in proximal third tibia in 27, middle third in two and distal third in nine patients. The diagnosis was giant cell tumor in 32, chondroblastoma in three, chondromyxoid fibroma, enchondroma and desmoplasic fibroma in one patient each. The resection was intercalary in 28 and transarticular in 10 patients. Osteosynthesis was monofocal in three, bifocal in 31 and polyfocal in four cases. RESULTS: Mean followup was 7.22 years (range 1.5 15 years). Mean resection length was 10.21 cm (range 3-22 cm). The mean duration of external fixator was 308.03 days (range 89-677 days) and mean external fixator index was 36.14 days/cm (range 16.84-97.43 days/cm). Twelve patients had difficulties in the form of 11 problems and five obstacles that were successfully managed. None of the patients had local recurrence of tumor or any long term complication. Mean Musculo-skeletal Tumour Society score at final followup was 27.18 (90.60%). CONCLUSIONS: Bone transport is an excellent option after resection of benign tumors of tibia with good local control and functional outcome, despite minor difficulties that need timely management. PMID- 26538758 TI - Condylar orientation plating in comminuted intraarticular fractures of adult distal humerus. AB - BACKGROUND: The condyles of the distal humerus have characteristic orientation in reference to the diaphysis. Anatomical reduction of the articular surface in intraarticular fractures of adult distal humerus does not always restore preinjury functional status. The purpose of this study was to determine the outcome of treating these fractures with technique of condylar orientation precontoured plating. The principle of the technique is to primarily restore the anatomical orientation of the reconstructed distal humeral condyle with the diaphysis of the humerus apart from anatomical reduction of fracture. MATERIALS AND METHODS: Seventy one consecutive patients with comminuted intraarticular adult distal humerus fractures were treated with the condylar orientation plates, which were specifically designed between 1999 and 2009. 43 fractures were Association for osteosynthesis (AO) type C3, 24 were C2 and 4 were C1. Six were open cases and two were of nonunion distal end humerus. On medial and posterolateral side of the distal humerus, precontoured Sherman plates were applied. Patients were followed up for a mean of 3 years. They were assessed clinically (using mayo elbow performance score [MEPS]) and radio-graphically. RESULTS: Sixty (84.5%) patients regained MEPS of 90 or more that is an excellent result (range of movement and functional status). One patient had nonunion with implant failure, and two patients developed heterotopic ossification. The mean MEPS was 95. Average extension and flexion was 15 degrees and 133 degrees . The result was graded as excellent in 60, good in 7, fair in 3 and poor in 1. At the time of most recent followup, 63 elbows were painless, and eight had mild pain. CONCLUSION: Excellent pain free range of motion with a high rate of union can be achieved in comminuted intraarticular distal humerus fractures in adults with the use of condylar orientation precontoured plating technique. Condylar orientation is very important with perfect articular congruity in elbow motion. PMID- 26538759 TI - Early results of displaced supracondylar fractures of humerus in children treated by closed reduction and percutaneous pinning. AB - BACKGROUND: Displaced supracondylar fractures are notorious for difficulty in reduction, maintenance of reduction and frequent involvement of neurovascular structures. No general agreement on the treatment is evident with controversy prevailing regarding the ideal timing of surgery, method of maintenance of reduction and configuration of the pin fixation. A crossed pin configuration, though believed by some to be mechanically more stable than the lateral pins alone, has the risk of ulnar nerve injury due to the medial pin. Lateral pins alone impart less rotational stability to the fracture although it has been attributed mainly to technical errors of pin placement. The aim of this study was to assess the efficacy of treatment of this fracture using one lateral and one trans-olecranon K-wires or lateral entry K-wires alone. MATERIALS AND METHODS: Ninety cases of displaced supracondylar humerus fractures were included in the study. The mean age of the patients was 6.7 years (range 3-12 years). The male/female ratio was 5:1 and left side was involved in 70% whereas 30% had right sided injuries. The most common mode of trauma was fall from height with elbow in extension. All the 90 consecutively admitted patients had extension type injury with 73.3% fractures being Gartland type III and 26.7% were type II. Posteromedial displacement was noted in 70% whereas 30% fractures were posterolaterally displaced. In 60 cases, lateral entry wires alone were used whereas, in 30 cases, one lateral and another transolecranon transarticular K wire was used. K-wires were removed at 3 weeks postoperatively and followup was done at 6 weeks and 12 weeks when they were evaluated according to the criteria described by Flynn. Chi-square test was used as a statistical test of significance to compare results among different variables. RESULTS: Results were graded according to Flynn's criteria. Excellent results were achieved in 12 (13.3%), good in 54 (60%), fair in 15 (16.7%) while in nine patients (10%) poor results were obtained. CONCLUSIONS: Both lateral entry K-wires and lateral-trans olecranon wire techniques provide stable fixation when observing the guidelines for wire placement and consistently satisfactory results can be obtained, both cosmetically and functionally with both the techniques. PMID- 26538760 TI - Two peg spade plate for distal radius fractures: A novel technique. AB - BACKGROUND: The management of distal radius fractures raises considerable debate among orthopedic surgeons. The amount of axial shortening of the radius correlates with the functional disability after the fracture. Furthermore, articular incongruity has been correlated with the development of arthritis at the radiocarpal joint. We used two peg volar spade plate to provide a fixed angle subchondral support in comminuted distal radius fractures with early mobilization of the joint. MATERIALS AND METHODS: Forty patients (26 males and 14 females) from a period between January 2009 and December 2011 were treated with two peg volar spade plate fixation for distal radius fracture after obtaining reduction using a mini external fixator. Patients were evaluated using the demerit point system of Gartland and Werley and Sarmiento modification of Lindstrom criteria at final followup of 24 months. RESULTS: The average age was 43.55 years (range 23 57 years). Excellent to good results were seen in 85% (n = 34) and in all patients when rated according to the demerit point system of Gartland and Werley and Sarmiento modification of Lindstrom criteria, respectively. Complications observed were wrist stiffness in 5% (n = 2) and reflex sympathetic dystrophy in 2.5% (n = 1). CONCLUSIONS: The two peg volar spade plate provides a stable subchondral support in comminuted intraarticular fractures and maintains reduction in osteoporotic fractures of the distal radius. Early mobilization with this implant helps in restoring wrist motion and to prevent development of wrist stiffness. PMID- 26538761 TI - Outcome of low level lasers versus ultrasonic therapy in de Quervain's tenosynovitis. AB - BACKGROUND: de Quervain's tenosynovitis is an inflammation of abductor pollicis longus (APL) and extensor pollicis brevis (EPB) muscle tendon sheaths at the level of radial styloid process. Its conservative management includes nonsteroidal anti-inflammatory drugs, wrist and thumb immobilization, ultrasonic therapy (US Th.) and low level laser therapy (LLLT). Literature is scanty on comparative efficacy of US Th. and LLLT for its management. This prospective study evaluates outcome of US Th. versus LLLT in de Quervain's disease. MATERIALS AND METHODS: Thirty patients clinically diagnosed de Quervains tenosynovitis were included in the study and randomly assigned to two groups. The average age was 36 years (range: 21-45 years). One group was given LLLT and the other US Th. for a total of 7 exposures on alternate days. The clinical criteria used were Finkelstein's test, tenderness over radial styloid (Ritchie's tenderness scale), grip strength, pain (visual analog scale [VAS]) and radiological criteria was ultrasonographic assessment of change in thickness of APL and EPB tendon sheath. They were measured before commencement and at the end of seven sessions of therapy, as per standard procedure. RESULTS: Significant improvement was seen within both groups in the following outcome measures assessed: Ritchie's tenderness scale, grip strength and VAS. Finkelstein's test was not significantly improved in either groups. Ultrasonographic measurement of tendon sheath diameters, the mediolateral (ML), and anteroposterior (AP) diameters was not found to be significantly different in the US Th. group and the laser therapy group after treatment. On comparing both the groups, no statistically significant difference was found. However, looking at the mean values, the grip strength and VAS showed better improvement in the US Th. group as compared to the laser therapy group. PMID- 26538762 TI - Anatomical variation of abductor pollicis longus in Indian population: A cadaveric study. AB - BACKGROUND: Many authors have reported the anatomical variation of abductor pollicis longus (APL) around the wrist and its association with de Quervain tenosynovitis (DQT), first carpo-metacarpal arthritis, and trapezio-metacarpal subluxation. From Indian subcontinent, there is only one original article and a few case reports on the variability of APL tendon insertion. MATERIALS AND METHODS: Fifty formaldehyde preserved cadaveric wrists were dissected to look for the anatomical variation of APL in the Indian population. RESULTS: The APL was found with single tendon in 2, double in 31, triple in 8, and quadruple in 8 extremities. A maximum of 6 tendon-slips were found in one cadaveric wrist. In all hands, the APL had at least one attachment to first metacarpal bone and in 46 hands (92%), there was second insertion to the trapezium bone. Of all tendon slips of APL (n = 126), 44% of tendons (68 tendons) were inserted into the base of the first metacarpal bone. This was followed by the insertion into the trapezium in 42% tendons (52 tendons). CONCLUSION: Bi-tendinous APL is commonly observed on the dorsal compartment of the wrist in Indian population and these tendon-slips are commonly attached to the first metacarpal base and trapezium. This variation must be understood by the Indian Orthopedic surgeons as the response to treatment of DQT and reason for first carpo-metacarpal arthritis can be dependent on this anatomical variation. PMID- 26538763 TI - Use of tubulization (nerve conduits) in repairing nerve defects in children. AB - BACKGROUND: Direct neurorrhaphy, nerve grafting interposition and neurotization are the options for nerve repair in children, whereas few reports about using nerve conduits (tubulization) are referred to pediatrics in the literature. The authors present their experience about nerve repairing by means of nerve tubes during the developmental age when the harvesting of nerve grafts and also vein grafts of adequate caliber for bridging nerve defects is difficult. A critical review of their case series offers indications for using nerve conduits in pediatrics. MATERIALS AND METHODS: Fifteen patients were treated using the nerve tubulization; nine patients were affected by obstetrical brachial plexus palsy (OBPP) while six were suffering from peripheral nerve injuries (PNIs). RESULTS: In patients suffering from OBPP, we observed 1 good, 3 fair and 5 bad results. In the PNI group, we observed 4 patients who had good results while only 2 had a bad outcome. No fair results were observed. CONCLUSIONS: In peripheral nerve repairing in children by using nerve conduits, the outcome has been widely effective even when dealing with mixed and motor nerve, thus nerve tubulization might be considered as an alternative to nerve grafting. Conversely, considering the uncertain result obtained in brachial plexus repairing, the conduits cannot be considered as a first choice of treatment in brachial plexus reconstruction. PMID- 26538765 TI - Total knee arthroplasty in vascular malformation. AB - In Klippel-Trenaunay syndrome, vascular malformations are not only in skin and superficial soft tissues but also in deep tissues like muscles bones and joints. It is well documemted that these recurrent intraarticular bleeds can cause early arthritis and joint pain. Performing arthroplasty in such patients is difficult and fraught with complications. We describe such a case where navigated total knee arthroplasty was performed with success to avoid the problems of intra medullary alignment used in the presence of intra medullary vascular malformations. We also suggest certain measures when knee arthroplasty is considered in such patients. PMID- 26538766 TI - Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome. AB - Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment. PMID- 26538764 TI - Evaluation of the ability of natural and synthetic scaffolds in providing an appropriate environment for growth and chondrogenic differentiation of adipose derived mesenchymal stem cells. AB - BACKGROUND: Although progenitor cells have been observed in articular cartilage, this part has a limited ability to repair due to a lack of blood supply. Formerly, tissue engineering was mainly based on collecting chondrocytes from the joint surface, culturing them on resorbable scaffolds such as poly D, L-lactic glycolic acid (PLGA) and then autologous transplantation. In recent times, due to difficulties in collecting chondrocytes, most of the researchers are focused on stem cells for producing these cells. Among the important factors in this approach, is using appropriate scaffolds with good mechanical and biological properties to provide optimal environment for growth and development of stem cells. In this study, we evaluated the potential of fibrin glue, PLGA and alginate scaffolds in providing a suitable environment for growth and chondrogenic differentiation of mesenchymal stem cells (MSCs) in the presence of transforming growth factor-beta3. MATERIALS AND METHODS: Fibrin glue, PLGA and alginate scaffolds were prepared and MSCs were isolated from human adipose tissue. Cells were cultured separately on the scaffolds and 2 weeks after differentiation, chondrogenic genes, cell proliferation ability and morphology in each scaffold were evaluated using real time-polymerase chain reaction, MTT chondrogenic assay and histological examination, respectively. RESULTS: Proliferation of differentiated adipose tissue derived mesenchymal stem cells (AD MSCs) to chondrogenic cells in Fibrin glue were significantly higher than in other scaffolds. Also, Fibrin glue caused the highest expression of chondrogenic genes compared to the other scaffolds. Histological examination revealed that the pores of the Fibrin glue scaffolds were filled with cells uniformly distributed. CONCLUSION: According to the results of the study, it can be concluded that natural scaffolds such as fibrin can be used as an appropriate environment for cartilage differentiation. PMID- 26538767 TI - Teacher (Mis)Perceptions of Preschoolers' Academic Skills: Predictors and Associations With Longitudinal Outcomes. AB - Preschool teachers have important impacts on children's academic outcomes, and teachers' misperceptions of children's academic skills could have negative consequences, particularly for low-income preschoolers. This study utilized data gathered from 123 preschool teachers and their 760 preschoolers from 70 low income, racially diverse centers. Hierarchical linear modeling was utilized to account for the nested data structure. Even after controlling for children's actual academic skill, older children, children with stronger social skills, and children with fewer inattentive symptoms were perceived to have stronger academic abilities. Contrary to hypotheses, preschoolers with more behavior problems were perceived by teachers to have significantly better pre-academic abilities than they actually had. Teachers' perceptions were not associated with child gender or child race/ethnicity. Although considerable variability was due to teacher-level characteristics, child characteristics explained 42% of the variability in teachers' perceptions about children's language and pre-literacy ability and 41% of the variability in teachers' perceptions about mathability. Notably, these perceptions appear to have important impacts over time. Controlling for child baseline academic skill and child characteristics, teacher perceptions early in the preschool year were significantly associated with child academic outcomes during the spring for both language and pre-literacy and math. Study implications with regard to the achievement gap are discussed. PMID- 26538768 TI - Supramolecular Magnetic Brushes: The Impact of Dipolar Interactions on the Equilibrium Structure. AB - The equilibrium structure of supramolecular magnetic filament brushes is analyzed at two different scales. First, we study the density and height distributions for brushes with various grafting densities and chain lengths. We use Langevin dynamics simulations with a bead-spring model that takes into account the cross links between the surface of the ferromagnetic particles, whose magnetization is characterized by a point dipole. Magnetic filament brushes are shown to be more compact near the substrate than nonmagnetic ones, with a bimodal height distribution for large grafting densities. This latter feature makes them also different from brushes with electric dipoles. Next, in order to explain the observed behavior at the filament scale, we introduce a graph theory analysis to elucidate for the first time the structure of the brush at the scale of individual beads. It turns out that, in contrast to nonmagnetic brushes, in which the internal structure is determined by random density fluctuations, magnetic forces introduce a certain order in the system. Because of their highly directional nature, magnetic dipolar interactions prevent some of the random connections to be formed. On the other hand, they favor a higher connectivity of the chains' free and grafted ends. We show that this complex dipolar brush microstructure has a strong impact on the magnetic response of the brush, as any weak applied field has to compete with the dipole-dipole interactions within the crowded environment. PMID- 26538769 TI - Modeling Short- and Long-Term Characteristics of Follicle Stimulating Hormone as Predictors of Severe Hot Flashes in Penn Ovarian Aging Study. AB - The Penn Ovarian Aging Study tracked a population-based sample of 436 women aged 35-47 years to determine associations between reproductive hormone levels and menopausal symptoms. We develop a joint modeling method that uses the individual level longitudinal measurements of follicle stimulating hormone (FSH) to predict the risk of severe hot flashes in a manner that distinguishes long-term trends of the mean trajectory, cumulative changes captured by the derivative of mean trajectory, and short-term residual variability. Our method allows the potential effects of longitudinal trajectories on the health risks to vary and accumulate over time. We further utilize the proposed methods to narrow the critical time windows of increased health risks. We find that high residual variation of FSH is a strong predictor of hot flash risk, and that the high cumulative changes of the FSH mean trajectories in the 52.5-55 year age range also provides evidence of increased risk above and beyond that of short-term FSH residual variation by itself. PMID- 26538770 TI - Mothers' Partnership Instability and Coparenting among Fragile Families. AB - OBJECTIVES: The rise in nonmarital childbearing has raised concerns about coparenting among unmarried parents with increasingly complicated relationship trajectories. We address this issue by examining associations between mothers' partnership transitions and coparenting and the moderating role of maternal race/ethnicity and child gender. METHODS: Data from the Fragile Families Study and ordinary least squares regression techniques are used to examine whether mothers' partnership transitions are related to coparenting. Lagged and fixed effects models are employed to test the robustness of the findings to selection. RESULTS: Coresidential and nonresidential, dating transitions are negatively associated with coparenting, but the association is stronger for coresidential transitions than for dating transitions. Coresidential transitions are stronger predictors of coparenting for White parents than for Black parents and for parents of sons than for parents of daughters. CONCLUSIONS: Policies aimed at strengthening families should emphasize relationship stability, regardless of the type of union, to promote high quality coparenting among at-risk populations. PMID- 26538771 TI - A Two-Piece Microkeratome-Assisted Mushroom Keratoplasty Improves the Outcomes and Survival of Grafts Performed in Eyes with Diseased Stroma and Healthy Endothelium (An American Ophthalmological Society Thesis). AB - PURPOSE: To test the hypothesis that a new microkeratome-assisted penetrating keratoplasty (PK) technique employing transplantation of a two-piece mushroom shaped graft may result in better visual outcomes and graft survival rates than those of conventional PK. METHODS: Retrospective chart review of 96 eyes at low risk and 76 eyes at high risk for immunologic rejection (all with full-thickness central corneal opacity and otherwise healthy endothelium) undergoing mushroom PK between 2004 and 2012 at our Institution. Outcome measures were best-corrected visual acuity (BCVA), refraction, corneal topography, endothelial cell density, graft rejection, and survival probability. RESULTS: Five years postoperatively, BCVA of 20/40 and 20/20 was recorded in 100% and over 50% of eyes, respectively. Mean spherical equivalent of refractive error did not vary significantly over a 5 year period; astigmatism averaged always below 4 diopters, with no statistically significant change over time, and was of the regular type in over 90% of eyes. Endothelial cell density decreased to about 40% of the eye bank count 2 years after mushroom PK and did not change significantly thereafter. Five years postoperatively, probabilities of graft immunologic rejection and graft survival were below 5% and above 95%, respectively. There was no statistically significant difference in endothelial cell loss, graft rejection, and survival probability between low-risk and high-risk subgroups. CONCLUSIONS: Refractive and visual outcomes of mushroom PK compare favorably with those of conventional full thickness keratoplasty. In eyes at high risk for immunologic rejection, mushroom PK provides a considerably higher probability of graft survival than conventional PK. PMID- 26538772 TI - The Global Education Network for Retinopathy of Prematurity (Gen-Rop): Development, Implementation, and Evaluation of A Novel Tele-Education System (An American Ophthalmological Society Thesis). AB - PURPOSE: To describe the design, implementation, and evaluation of a tele education system developed to improve diagnostic competency in retinopathy of prematurity (ROP) by ophthalmology residents. METHODS: A secure Web-based tele education system was developed utilizing a repository of over 2,500 unique image sets of ROP. For each image set used in the system, a reference standard ROP diagnosis was established. Performance by ophthalmology residents (postgraduate years 2 to 4) from the United States and Canada in taking the ROP tele-education program was prospectively evaluated. Residents were presented with image-based clinical cases of ROP during a pretest, posttest, and training chapters. Accuracy and reliability of ROP diagnosis (eg, plus disease, zone, stage, category) were determined using sensitivity, specificity, and the kappa statistic calculations of the results from the pretest and posttest. RESULTS: Fifty-five ophthalmology residents were provided access to the ROP tele-education program. Thirty-one ophthalmology residents completed the program. When all training levels were analyzed together, a statistically significant increase was observed in sensitivity for the diagnosis of plus disease, zone, stage, category, and aggressive posterior ROP (P<.05). Statistically significant changes in specificity for identification of stage 2 or worse (P=.027) and pre-plus (P=.028) were observed. CONCLUSIONS: A tele-education system for ROP education is effective in improving diagnostic accuracy of ROP by ophthalmology residents. This system may have utility in the setting of both healthcare and medical education reform by creating a validated method to certify telemedicine providers and educate the next generation of ophthalmologists. PMID- 26538773 TI - Donor Corneal Transplantation vs Boston Type 1 Keratoprosthesis in Patients with Previous Graft Failures: A Retrospective Single Center Study (An American Ophthalmological Society Thesis). AB - PURPOSE: To compare short-term outcomes of repeat penetrating keratoplasty (PK) to those of Boston type 1 keratoprosthesis (KPro). Our hypothesis was that visual outcomes were superior for KPro compared to PK. METHODS: This is a retrospective, nonrandomized, intermediate-term case series. Consecutive adults with one or more failed PKs who underwent either PK or KPro between January 2008 and December 2010 were included. Demographics, indication for the initial PK, comorbidities, concomitant procedures, and complications were considered. Only one procedure in each eye was included. All KPro procedures were retained in the analyses. RESULTS: Fifty-three patients underwent PK and 27 received KPro. Mean follow-up was 19.5 months in the PK group and 16.5 months in the KPro group. KPro eyes had worse mean preoperative vision (hand motions vs counting fingers, P=.01) and more comorbidities. In the postoperative period, 35% of PK eyes and 45% of KPro eyes attained best-ever visual acuity of 20/70. Forty-seven percent of PK eyes vs 40% of KPro eyes were able to retain this visual acuity. Two-year rate of failure to retain visual acuity better than the baseline was higher for PK eyes, though not at a statistically significant level (hazard ratio [HR]=1.67; 95% CI, 0.78-3.60; P=.19). Two-year cumulative rate of graft failure (loss of clarity for PK and removal/replacement for KPro) was higher for PK eyes (HR=3.23; 95% CI, 1.12-9.28; P=.03). Retinal detachment, endophthalmitis, and glaucoma rates were similar (P=.6 for all). CONCLUSIONS: These results demonstrate less frequent graft failure, greater visual improvement, and greater likelihood of maintaining the visual improvement in KPro eyes vs PK. PMID- 26538775 TI - Evaluation of the Efficacy of Topical Ethyl Vanillate in Enhancing the Effect of Narrow Band Ultraviolet B against Vitiligo: A Double Blind Randomized, Placebo Controlled Clinical Trial. AB - BACKGROUND: Vitiligo is an acquired disease of skin that presents with depigmented patches due to lack of melanocytes in the epidermis. Accumulation of toxic free radicals like hydrogen peroxide in the epidermis may be responsible for melanocytes death. Since ethyl vanillate (vanillic acid ethyl ester) is a strong hydrogen peroxide scavenger, it may be effective against vitiligo. This study was carried out to evaluate the effect of ethyl vanillate cream on vitiligo patients receiving phototherapy. METHODS: A double-blind placebo-controlled clinical trial using ethyl vanillate cream 20% was performed on 30 cases of generalized stable vitiligo (randomly selected) who were receiving phototherapy in the outpatient clinic of Faghihi Hospital (Shiraz, Iran). The patients randomly applied ethyl vanillate on an assigned lesion (left or right side of the body) and placebo on the opposite side lesion (almost the same size and location) twice a day for 3 months, while receiving a narrow band ultraviolet B (NB-UVB) 2 3 times weekly. Photos were taken at the beginning of the trial and at the end of 4(th), 8(th), and 12(th) weeks. Then, images were compared with the photos from the beginning of the trial based on VASI score. RESULTS: There was a significant change in pigmentation after applying ethyl vanillate compared with baseline in medication side (P=0.002), but no significant change in placebo side (P=0.066). Additionally, there was a significant difference between medication and placebo sides in pigmentation (P=0.005). CONCLUSION: Ethyl vanillate may serve as an adjunct therapy for the treatment of vitiligo, although changes in pigmentation are mild clinically. PMID- 26538774 TI - Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis). AB - PURPOSE: To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). METHODS: Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. "Wild-type Lp(a)" mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and "mutant LBS(-) Lp(a)" mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid-containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. RESULTS: Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS(-) Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators. CONCLUSIONS: Human maculas accumulate Lp(a) and OxPL. Mutant LBS(-) Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD. PMID- 26538777 TI - No Definite Association between Human Parvovirus B19 Infection and Behcet Disease. AB - BACKGROUND: The etiology of the Behcet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. MATERIALS AND METHODS: We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. RESULTS: Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. CONCLUSION: Our data could not establish an association between B19 parvovirus infection and Behcet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy. PMID- 26538776 TI - Early Acute Kidney Injury based on Serum Creatinine or Cystatin C in Intensive Care Unit after Major Trauma. AB - BACKGROUND: Acute kidney injury (AKI) is a common problem in critically ill patients and is independently associated with increased morbidity and mortality. Recently, serum cystatin C has been shown to be superior to creatinine in early detection of renal function impairment. We compared estimated GFR based on serum cystatin C with estimated GFR based on serum creatinine for early detection of renal dysfunction according to the RIFLE criteria. METHODS: During 9 months, three hundred post trauma patients that were referred to the intensive care unit of a referral trauma hospital were recruited. Serum creatinine and serum cystatin C were measured and the estimated GFR within 24 hours of ICU admission was calculated. The primary outcome was the incidence of AKI according to the RIFLE criteria within 2(nd) to 7(th) day of admission. RESULTS: During the first week of ICU admission, 21% of patients experienced AKI. After adjusting for major confounders, only the patients with first day's serum cystatin level higher than 0.78 mg/l were at higher risk of first week AKI (OR=6.14, 95% CI: 2.5-14.7, P<0.001). First day's serum cystatin C and injury severity score were the major risk factors for ICU mortality (OR=3.54, 95% CI: 1.7-7.4, P=0.001) and (OR=4.6, 95% CI: 1.5-14, P=0.007), respectively. CONCLUSION: Within 24 hours after admission in ICU due to multiple trauma, high serum cystatin C level may have prognostic value in predicting early AKI and mortality during ICU admission. However, such correlation was not seen neither with creatinine nor cystatin C based GFR. PMID- 26538778 TI - Inhibitory Effects of Silver Nanoparticles on Growth and Aflatoxin B1 Production by Aspergillus Parasiticus. AB - BACKGROUND: Aflatoxins (AFs) are secondary hazardous fungal metabolites that are produced by strains of some Aspergillus species on food and feedstuffs. Aflatoxin B1 (AFB1) is one of the most important AF with high toxicity. Prevention of AF production and their elimination from food products is a matter of importance for many researchers in the last decades. Nanomaterials applications in medical science have been widely studied in the recent years. Most of existing researches seek the effect of nanoparticles on bacteria, fungi, and viruses. The aim of this study was to determine the effects of silver nanoparticles (AgNPs) on growth and AFB1 production of AF-producing Aspergillus parasiticus. METHODS: A parasiticus was inoculated (10(6) conidia per ml of medium) to potato dextrose broth (PDB) medium and then AgNPs was added and incubated with shaking at 130 rpm and 28 degrees C for 7 days. AF was assayed by high performance liquid chromatography (HPLC). Microbiological assay (MBA) on microplates contained potato dextrose broth (PDB) medium (4 days at 28 degrees C) at different concentrations of AgNPs (60, 80, 100, 120, 140, 160, 180 and 200 MUg/ml) was measured. RESULTS: The results demonstrated that a minimum inhibition concentration (MIC) equal to 180 MUg/ml was determined for AgNPs against A. parasiticus. The AgNPs effectively inhibited AFB1 production at a concentration of 90 MUg/ml. CONCLUSION: The results obtained in this study show AgNPs at concentrations lower than the MIC drastically inhibited production of AFB1 by A. parasiticus in culture medium. The AgNPs may be useful to control AF contamination of susceptible crops in the field. PMID- 26538779 TI - Progesterone Enhanced Remyelination in the Mouse Corpus Callosum after Cuprizone Induced Demyelination. AB - BACKGROUND: Progesterone as a sex steroid hormone is thought to affect and prevent demyelination, but its role in promoting myelin repair is far less investigated. In this study, remyelinating potential of progesterone in corpus callosum was evaluated on an experimental model of MS. METHODS: In this experimental study, adult male C57BL/6 mice were fed with 0.2% (w/w) cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after cuprizone removal, mice were divided randomly into two groups: (a) placebo group, which received saline pellet implant, (b) progesterone group, which received progesterone pellet implant. Some mice of the same age were fed with their normal diet to serve as the healthy control group. Two weeks after progesterone administration, Myelin content was assessed by Luxol-fast blue staining. The myelin basic protein (MBP) and proteolipid protein (PLP) expression were assessed using Western blot analysis and the changes in the number of oligodendrocytes and oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC) and flow cytometry. RESULTS: Luxol-fast blue staining revealed enhanced remyelination in the progesterone group when compared with the placebo group. Densitometry measurements of immunoblots demonstrated that MBP and PLP proteins contents were significantly increased in the progesterone group compared with the placebo group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in the progesterone group compared with the placebo group. CONCLUSION: Overall, our results indicate that progesterone treatment can stimulate myelin production and that it may provide a feasible and practical way for remyelination in diseases such as multiple sclerosis. PMID- 26538780 TI - Prevalence of qnr and aac(6')-Ib-cr Genes in Clinical Isolates of Klebsiella Pneumoniae from Imam Hussein Hospital in Tehran. AB - BACKGROUND: Plasmid mediated quinolone resistance (PMQR) has been shown to play an important role in resistance not only to quinolones, but also beta-lactams and aminoglycosides. In fact, qnr genes are frequently carried along with beta lactamase determinants on the same plasmids. We studied the prevalence of qnrA, qnrB, qnrS and aac(6')-Ib-cr genes among quinolone and cephalosporin resistant clinical isolates of Klebsiella pneumoniae (K. pneumoniae), as well as the association between PMQR genes with resistance to quinolones, cephalosporins and aminoglycosides. METHODS: The study was conducted on 79 K. pneumoniae clinical isolates collected from Imam Hussein hospital in Tehran between July 2010 and January 2011, based on their resistance to quinilones and cephalosporins. Antibacterial susceptibility was determined to 15 antibiotics by disc diffusion. Presence of qnrA, qnrB, qnrS and aac(6')-Ib-cr genes were investigated using specific primers and PCR. RESULTS: Of the 79 K. pneumoniae isolates, 47 (59.5%) carried the PMQR determinants. Among these, 42 (89.4%) carried aac(6')-Ib-cr of which, 21 (50%) also harbored qnrB. Three isolates carried qnrB alone, two (4.2%) harbored qnrS and none had qnrA. Resistance to aminoglycosides and cephalosporins was significantly higher in the isolates carrying both qnrB and aac(6')-Ib-cr genes compared to aac(6')-Ib-cr alone. CONCLUSION: This study showed a high prevalence of aac(6')-Ib-cr and qnrB genes among the Iranian K. pneumoniae clinical isolates as well as co-carriage of the two genes. There was a significant association between qnrB gene carriage and resistance to quinolones, cephalosporins, and aminoglycosides. PMID- 26538781 TI - The Prevalence of Metabolic Syndrome According to Different Criteria and its Associated Factors in Type 2 Diabetic Patients in Kerman, Iran. AB - Metabolic syndrome is highly prevalent in type 2 diabetics and is a strong risk factor for cardiovascular diseases in such patients. The aim of this study was to determine the prevalence of metabolic syndrome according to the three criteria of ATPIII, IDF and the new criteria for metabolic syndrome diagnosis in Kerman, Iran. This cross-sectional study was performed on 950 diabetic type 2 patients. Data was analyzed by independent t-test, chi-square and logistic regression using the SPSS (revision 20) software. The prevalence of metabolic syndrome in Kerman was 73.4, 64.9, and 70.4%, according to the above criteria. Fasting blood sugar, gender, triglyceride, HDL, waist circumference, and systolic blood pressure were related to the prevalence of metabolic syndrome according to the above-mentioned criteria.The prevalence of metabolic syndrome is high in type 2 diabetic patients and the above-mentioned factors exacerbate the situation. PMID- 26538782 TI - Isolation of Methicillin-Resistant Staphylococcus aureus (MRSA) from HIV Patients Referring to HIV Referral Center, Shiraz, Iran, 2011-2012. AB - Extension of drug resistant Staphylococcus aureus strains is one of the problems of modern society. Presence of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected individuals is an important cause of severe infections. Therefore, the main goal of this study was to determine the prevalence rate of MRSA carriage rate among HIV patients referring to the Shiraz HIV referral center (Shiraz, Iran) during 2011-2012. Nasal swabs were obtained from HIV positive patients and were cultured on differential and selective media to isolate Staphylococcus aureus, which was confirmed by standard biochemical tests. For isolation of MRSA isolates, bacterial suspensions were cultured on Muller-Hinton Agar containing NaCl and Oxacillin. Finally, data were analyzed by the SPSS software. Of 180 HIV patients, MRSA was isolated from nasal cavity of 23 (12.8%) patients. Most of the isolates were recovered from male subjects who were under 40 years old. No variables such as skin disease, history of hospitalization or infectious disease had significant association with the MRSA colonization rate. The presence of MRSA isolates in the nasal cavity of HIV patients in such a rate warns us about the potential spreading of MRSA among HIV patients in our society and emphasizes on establishing better prevention strategies. PMID- 26538783 TI - Yazd Breast Cancer Project Profile; A Community Based Trial for the Evaluation of Self-Examination and Physical Examination of the Breast Cancer Disease. AB - There is some evidence to suggest that a benefit might be derived from a program that incorporated both annual physical examination of the breast (BPx) and the teaching of breast self-examination (BSE). Current investigation presents the profile of a multicenter community based intervention for evaluating the effect of BSE+BPx on the reduction of morbidity and mortality due to breast cancer amongst women residing in urban areas of Yazd (Iran) from 2008 to 2018. There were three distinctive phases in this trial with 10 years duration: pilot phase with the duration of 1 year, active intervention phase with 4 rounds of annual screening of BPx+BSE and follow up phase with 5 years duration. Tools of enquiry included a pre-tested questionnaire, repeated annual physical examination of the breast and more importantly mammography, sonography, and fine needle aspiration (FNA). Data were analyzed using descriptive statistics such as frequencies, percent, mean (SD), tests of chi-square and student t-test with 95% confidence level. Comparison of socio-demographic and socio-economic factors such as age, age at marriage, family size, number of live births, occupation, education level, total family income and marital status showed that no significant difference was seen between the groups (P>0.05). A response rate of 84.5% was seen by participants of the experiment group visiting the health centers for the first BPx. Our results showed that except for the education and marital status, the difference in other main demographic and socio-economic factors between the groups were not significant, and the response rate of individuals in the experiment group was at an acceptable level. PMID- 26538784 TI - Spontaneous Unruptured Bilateral Tubal Pregnancy: A Case Report. AB - Bilateral spontaneous tubal ectopic pregnancy is the rarest form of extra uterine pregnancy. The diagnosis is usually made intraoperatively and levels of serum BHCG and ultrasound has not been useful in the diagnosis of bilateral tubal ectopic pregnancy. A 33-year-old woman with 8 weeks amenorrhea and sever lower abdominal pain was admitted. A transvaginal pelvic ultrasound revealed left adnexal mass and massive fluid collection in the pelvis and abdomen. The serum BHCG was 5,700 mIU/ml and in laparotomy bilateral unruptured tubal pregnancy was noted. Left salpingectomy and right salpingostomy were performed. The diagnosis of bilateral spontaneous tubal ectopic pregnancy is usually made intraoperatively. Both tubes at the time of surgery should be closely examined in order to prevent maternal morbidity and mortality. PMID- 26538785 TI - Primary Epidural Varicosis as a Rare Cause of Sciatica: A Case Report. AB - Non-discogenic sciatica can be caused by any lesion along the course of the lumbosacral nerve roots and sciatic nerve. We aim to present a rare case of refractory sciatica in an otherwise healthy 25-year-old man. He complained of left leg pain without significant back pain. Extensor hallucis longus muscle was weak on the left side with limited straight leg rising. On magnetic resonance imaging, a space-occupying lesion resembling a sequestrated disc was noted that after surgical decompression, epidural varicosis was demonstrated. PMID- 26538786 TI - Bilateral Abducent Palsy in Leptospirosis- An Eye Opener to a Rare Neuro Ocular Manifestation: A Case Report. AB - Leptospirosis, a disease of great significance in tropical countries, presents commonly as a biphasic illness with acute febrile episode in the first phase followed by a brief afebrile period and then by the second phase of fever with or without jaundice and renal failure. However, it has varied manifestations and unusual clinical features ascribed to immunological phenomena can occur due to the additional involvement of pulmonary, cardiovascular, and neurological systems. Among the various neurological features, aseptic meningitis is the most common myeloradiculopathy, myelopathy, cerebellar dysfunction, transverse myelitis, Guillain-Barre syndrome, optic neuritis, peripheral neuropathy hare also described. Cranial neuropathy involving facial nerve is a rare, but known neurological manifestation. Sixth nerve palsy in neuroleptospirosis has so far not been reported. We hereby present the occurrence of bilateral abducent nerve palsy in a patient with leptospirosis. PMID- 26538787 TI - Efficacy and Safety of Aripiprazole for Treatment of Irritability in Children with Autistic Disorder: An Open-Label Study. PMID- 26538788 TI - Bicornuate Zenker's Diverticulum. PMID- 26538789 TI - Evolutionary patterns of adaptive acrobatics and physical performance predict expression profiles of androgen receptor - but not oestrogen receptor - in the forelimb musculature. AB - 1. Superior physical competence is vital to the adaptive behavioral routines of many animals, particularly those that engage in elaborate socio-sexual displays. How such traits evolve across species remains unclear. 2. Recent work suggests that activation of sex steroid receptors in neuromuscular systems is necessary for the fine motor skills needed to execute physically elaborate displays. Thus, using passerine birds as models, we test whether interspecific variation in display complexity predicts species differences in the abundance of androgen and estrogen receptors (AR and ERalpha) expressed in the forelimb musculature and spinal cord. 3. We find that small-scale evolutionary patterns in physical display complexity positively predict expression of the AR in the main muscles that lift and retract the wings. No such relationship is detected in the spinal cord, and we do not find a correlation between display behavior and neuromuscular expression of ERalpha. Also, we find that AR expression levels in different androgen targets throughout the body - namely the wing muscles, spinal cord, and testes - are not necessarily correlated, providing evidence that evolutionary forces may drive AR expression in a tissue-specific manner. 4. These results suggest co-evolution between the physical prowess necessary for display performance and levels of AR expression in avian forelimb muscles. Moreover, this relationship appears to be specific to muscle and AR-mediated, but not ERalpha mediated, signaling. 5. Given that prior work suggests that activation of muscular AR is a necessary component of physical display performance, our current data support the hypothesis that sexual selection shapes levels of AR expressed in the forelimb skeletal muscles to help drive the evolution of adaptive motor abilities. PMID- 26538790 TI - The Reductive Activation of CO2 Across a Ti=Ti Double Bond: Synthetic, Structural, and Mechanistic Studies. AB - The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti2Pn?2 (1) (Pn? = 1,4-{SiiPr3}2C8H4) with CO2 is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO2 reaction is performed at -78 degrees C, the 1:1 adduct 4 is formed, and low temperature spectroscopic measurements are consistent with a CO2 molecule bound symmetrically to the two Ti centers in a MU:eta2,eta2 binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO2 is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a MU-O dimer in which the Ti-Ti bond has been cleaved and one pentalene ligand binds in an eta8 fashion to each of the formally TiIII centers. The molecular structure of 7 shows a "side-on" bound carbonyl ligand. Bonding of the double-sandwich species Ti2Pn2 (Pn = C8H6) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO2 reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-TiIII species to yield di-TiII and di-TiIV products. 1 forms a structurally characterized, thermally stable CS2 adduct 8 that shows symmetrical binding to the Ti2 unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(MU-S) mono(CO) species 10. Ph3PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(MU-S) complex 11 with a double-sandwich structure and bis(MU-S) dimer 12 in which the Ti-Ti bond has been cleaved. PMID- 26538791 TI - Bonding in Complexes of Bis(pentalene)dititanium, Ti2(C8H6)2. AB - Bonding in the bis(pentalene)dititanium "double-sandwich" species Ti2Pn2 (Pn = C8H6) and its interaction with other fragments have been investigated by density functional calculations and fragment analysis. Ti2Pn2 with C2v symmetry has two metal-metal bonds and a low-lying metal-based empty orbital, all three frontier orbitals having a1 symmetry. The latter may be regarded as being derived by symmetric combinations of the classic three frontier orbitals of two bent bis(cyclopentadienyl) metal fragments. Electrochemical studies on Ti2Pn?2 (Pn? = 1,4-{SiiPr3}2C8H4) revealed a one-electron oxidation, and the formally mixed valence Ti(II)-Ti(III) cationic complex [Ti2Pn?2][B(C6F5)4] has been structurally characterized. Theory indicates an S = 1/2 ground-state electronic configuration for the latter, which was confirmed by EPR spectroscopy and SQUID magnetometry. Carbon dioxide binds symmetrically to Ti2Pn2, preserving the C2v symmetry, as does carbon disulfide. The dominant interaction in Ti2Pn2CO2 is sigma donation into the LUMO of bent CO2, and donation from the O atoms to Ti2Pn2 is minimal, whereas in Ti2Pn2CS2 there is significant interaction with the S atoms. The bridging O atom in the mono(oxo) species Ti2Pn2O, however, employs all three O 2p orbitals in binding and competes strongly with Pn, leading to weaker binding of the carbocyclic ligand, and the sulfur analogue Ti2Pn2S behaves similarly. Ti2Pn2 is also capable of binding one, two, or three molecules of carbon monoxide. The bonding demands of a single CO molecule are incompatible with symmetric binding, and an asymmetric structure is found. The dicarbonyl adduct Ti2Pn2(CO)2 has Cs symmetry with the Ti2Pn2 unit acting as two MCp2 fragments. Synthetic studies showed that in the presence of excess CO the tricarbonyl complex Ti2Pn?2(CO)3 is formed, which optimizes to an asymmetric structure with one semibridging and two terminal CO ligands. Low-temperature 13C NMR spectroscopy revealed a rapid dynamic exchange between the two bound CO sites and free CO. PMID- 26538793 TI - Food and nutrition labelling in Thailand: a long march from subsistence producers to international traders. AB - This paper reviews the evolution of Thai food and nutrition label policies and Thailand's international role relating to food product safety and standards. The historical record has been interpreted to identify future trends and challenges related to food labelling. These challenges are arising in Thailand and many similar emerging economies. Thailand has a good reputation in world food markets and is now becoming a global leader in food production and export. It has become deeply involved with regulations and standards applied by World Trade Organization and Codex Alimentarius while serving its own population with a safe and secure food supply. For consumers considering Thai food products, food labels can provide useful nutrition information and help build trust. Thais began a century ago with policies and laws to enhance food safety and to protect Thai consumers. During the lengthy journey from national to global standards Thai food labels have evolved and now contribute to international food labelling policies. This contribution comes from the perspective of a leading middle income south east Asian food producer now trading with high income countries around the world. The story of that journey - a case study for many other countries in a similar situation - has not previously been told. This article provides information for policy makers dealing with food labelling, embedding trends and tensions for one middle income food exporter in a long history. Information captured here should be helpful for other middle income countries, especially those with limited records. This strategic knowledge will enable better decisions for future policies. PMID- 26538792 TI - Breath Hydrogen as a Biomarker for Glucose Malabsorption after Roux-en-Y Gastric Bypass Surgery. AB - OBJECTIVE: Abdominal symptoms are common after bariatric surgery, and these individuals commonly have upper gut bacterial overgrowth, a known cause of malabsorption. Breath hydrogen determination after oral glucose is a safe and inexpensive test for malabsorption. This study is designed to investigate breath hydrogen levels after oral glucose in symptomatic individuals who had undergone Roux-en-Y gastric bypass surgery. METHODS: This is a retrospective study of individuals (n = 63; 60 females; 3 males; mean age 49 years) who had gastric bypass surgery and then glucose breath testing to evaluate abdominal symptoms. RESULTS: Among 63 postoperative individuals, 51 (81%) had a late rise (>=45 minutes) in breath hydrogen or methane, supporting glucose malabsorption; 46 (90%) of these 51 subjects also had an early rise (<=30 minutes) in breath hydrogen or methane supporting upper gut bacterial overgrowth. Glucose malabsorption was more frequent in subjects with upper gut bacterial overgrowth compared to subjects with no evidence for bacterial overgrowth (P < 0.001). CONCLUSION: These data support the presence of intestinal glucose malabsorption associated with upper gut bacterial overgrowth in individuals with abdominal symptoms after gastric bypass surgery. Breath hydrogen testing after oral glucose should be considered to evaluate potential malabsorption in symptomatic, postoperative individuals. PMID- 26538794 TI - State Regulation, Family Breakdown, and Lone Motherhood: The Hidden Costs of World War I in Scotland. AB - Using a range of parish records, records from the Registrar General of Scotland, charity organizations, and media reports, this article contributes to the historiography which evaluates the effects of World War I in Britain as well as the history of lone mothers and their children. It highlights how during the war, women, especially lone mothers, made significant gains through the welfare system, changing approaches to illegitimacy and the plentiful nature of women's work but also how in doing so this brought them under greater surveillance by the state, local parishes, and charity organizations. Moreover, as this article will demonstrate, many of the gains made by women were short-lived and in fact the war contributed to high levels of family breakdown and gendered and intergenerational poverty endured by lone mothers and their children. PMID- 26538795 TI - Current Status of Robot-Assisted Radical Cystectomy: What is the Real Benefit? AB - In recent years, robot-assisted radical cystectomy has received attention worldwide as a useful procedure that helps to overcome the limitations of open radical cystectomy. We compared the surgical technique, perioperative and oncological outcomes, and learning curve of robot-assisted radical cystectomy with those of open radical cystectomy. The indications for robot-assisted radical cystectomy are identical to those of open radical cystectomy. Relative contraindications are due to patient positioning in the Trendelenburg position for long periods. Urinary diversion is performed either extracorporeally with a small skin incision or intracorporeally with a totally robotic-assisted maneuver. Accordingly, robot-assisted radical cystectomy can be performed safely with an acceptable operative time, little blood loss, and low transfusion rates. The lymph node yield and positive surgical margin rate were not significantly different between robot-assisted radical cystectomy and open radical cystectomy. The survival rates after robot-assisted radical cystectomy are estimated to be similar to that after open radical cystectomy. However, the recurrence pattern is different between robot-assisted radical cystectomy and open radical cystectomy, i.e., extrapelvic lymph node recurrence and peritoneal carcinomatosis were more frequently found in patients who underwent robot-assisted radical cystectomy than in those who underwent open radical cystectomy. Further validation is necessary to prove the feasibility of oncological control. A steep learning curve is one of the benefits of the new technique. The experience of only 50 robot-assisted radical prostatectomies is a minimum requirement for performing feasible robot assisted radical cystectomy, and surgeons who have performed only 30 surgeries can reach an acceptable level of quality for robot-assisted radical cystectomy. PMID- 26538796 TI - Opinions and Satisfaction Regarding Continuous Subcutaneous Insulin Infusion Therapy in Adult Patients with Type 1 Diabetes. AB - BACKGROUND: This study examined the treatment satisfaction of type 1 diabetic patients undergoing continuous subcutaneous insulin infusion (CSII) therapy, and patients' thoughts regarding CSII. METHODS: We provided a self-administered questionnaire survey over the internet. Participants were 106 individuals with type-one diabetes aged 20 years or older, undergoing CSII. The survey examined patients' treatment satisfaction, and their thoughts regarding CSII. Descriptive statistics were calculated. We compared relationships between treatment satisfaction and other variables using the Kruskal-Wallis rank sum test, and performed content analysis on participants' thoughts regarding CSII. RESULTS: Regarding treatment satisfaction, the response, "neither of them" was the most frequent. Comparing relationships between treatment satisfaction and other variables, significant differences were found for the variables "age," "presence of dissatisfaction regarding doctors' response," and "presence of a significant medical expense burden." Participants' thoughts regarding CSII were classified into 10 categories. CONCLUSION: Participants expressed positive evaluations, such as that their blood sugar control had improved due to CSII, and that they perceived improvement in their health. Participants also expressed negative evaluations, however, such as that medical expenses resulting from CSII were high, and that these expenses may cause distress and future economic insecurity. In future, patients may benefit from nursing support that allows patients to confidently continue with CSII. PMID- 26538797 TI - Water Quality Evaluation of PET Bottled Water by Mineral Balance in the Northeast Asian Region: A Case Study of South Korea. AB - BACKGROUND: The past few years have seen a demand for drinking water in contemporary society with a focus on safety and taste. Mineral water is now marketed as a popular commercial product and, partly due to health concerns, the production. METHODS: For the study, a comparison was carried out of water samples from 9 types of polyethylene terephthalate (PET) bottled water sold in South Korea as well as from tap water in the cities of Seoul and Chuncheon. These were compared with samples of Japanese PET bottled water in order to determine shared commonalities and identify individual characteristics. To evaluate water quality objectively, we quantified the elements contained in the water samples. Samples were assessed not with the usual sensory evaluation but with the evaluation approach advocated by Hashimoto et al. which employs the Water Index of Taste and the Water Index of Health. The levels of water quality obtained were compared with the "Prerequisites for Tasty Water" and the "Standards for Tasty Water" devised for city water. RESULTS: The PET Bottled water varieties analyzed in this study-Seoksu, Icis, Bong Pyong, Soon Soo 100, Dong Won Saem Mul, GI JANG SOO and DIAMOND-showed the Water Index of Taste >= 2.0 and the Water Index of Health >= 5.2, which we classified as tasty/healthy water. SamDaSoo and NamiNeral can be classified as tasty water due to their values of the Water Index of Taste >= 2.0 and the Water Index of Health < 5.2. CONCLUSION: The South Korean PET bottled water studied here fulfills the "Water Index of Taste," "Water Index of Health," "Standard for Tasty Water" and "Prerequisites for Tasty Water" that Japanese people value for city water. We can conclude that bottled water which meets water quality requirements will be considered good-tasting by a majority of people. PMID- 26538798 TI - Type 1 Diabetes Patients Using Continuous Subcutaneous Insulin Infusion Therapy: Feeling Burdened Correlated with Factors. AB - BACKGROUND: The purpose of this study was to investigate factors related to feelings of being burdened in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII) therapy. METHODS: Participants were 106 subscribers to the Diabetes Network's e-mail newsletter. An online survey was used. Eligible participants were aged at least 20 years, had type 1 diabetes, and were using CSII. Survey questions concerned whether participants found CSII burdensome, and seven potential reasons for feelings of burden. Analysis calculated correlations among participants' demographic and treatment-related factors, and among participants' reasons for feeling CSII to be burdensome. RESULTS: Regarding demographic and treatment-related factors, gender was found to be weakly negatively correlated with the following variables: employment status, and whether participants had discussed their concerns with a doctor. Employment status was found to be weakly correlated with diabetes duration; employment status and diabetes duration were found to be weakly correlated with age. Regarding reasons for finding CSII therapy burdensome, "It takes too much time" was found to be strongly positively correlated with "It interferes with work responsibilities"; 16 weak positive correlations were also found. CONCLUSION: To explain our results, we suggest that medical expenses, glycemic control, scheduling outpatient visits around home and work responsibilities, and interacting with medical staff may have caused participants to find CSII therapy burdensome. Most participants had never discussed their treatment concerns with a doctor. This suggests that nurses may be able to mitigate feeling burdened in participants using CSII therapy. PMID- 26538799 TI - The Effect of Bamboo Leaf Extract Solution and Sodium Copper Chlorophyllin Solution on Growth and Volatile Sulfur Compounds Production of Oral Malodor Associated Some Anaerobic Periodontal Bacteria. AB - BACKGROUND: Bamboo leaf extract solution (BLES) and sodium copper chlorophyllin solution (SCCS) are known for their anti-oxidant activities. Oral malodor is often related with periodontal pathogens. The present study was undertaken to investigate the anti-bacterial effect of both BLES and SCCS on anaerobic periodontal bacteria producing oral malodorous volatile sulfur compounds (VSC). METHODS: Porphyromonas gingivalis W83 (PG), Prevotella intermidai TDC19B (PI), Fusobacterium nucleatum ATCC25586 (FN) and Prevotella nigrescence ATCC33563 (PN) were investigated as oral isolated bacteria. VSC production ability of the oral strains was investigated by gas chromatography. With serial dilution of BLES or SCCS, the strains PG, PI, FN or PN were cultured anaerobically with AnaeroPack at 37 C for 3 days. For the determination of anti-bacterial action of BLES or SCCS, the inoculum was cultured with original concentrations of BLES 0.16% (w/v) or SCCS 0.25% (w/v). RESULTS: Gas chromatography exhibited that all strains, PG, PI, FN and PN were responsible for producing a high range of H2S and a moderate range of CH3SH. Anti-bacterial effect of BLES or SCCS on the strains was observed. Inhibition of BLES or SCCS on the strains was revealed as concentration dependent. BLES or SCCS inhibited bacterial proliferation at higher concentrations (PG; 0.04% BLES or 0.03% SCCS, PI; 0.002% BLES or 0.03% SCCS, FN; 0.005% BLES or 0.01% SCCS, PN; 0.01% BLES or 0.015% SCCS). No viable bacterial colony observed at original concentration of BLES 0.16% or SCCS 0.25%. Strain growth was eliminated from inhibition at lower concentrations (PG; 0.02% BLES or 0.015% SCCS, PI; 0.001% BLES or 0.015% SCCS, FN; 0.002% BLES or 0.007% SCCS, PN; 0.005% BLES or 0.007% SCCS). CONCLUSION: High concentrations of both BLES (0.16%) and SCCS (0.25%) show superior inhibiting capability on all four oral malodor associated periodontal anaerobes during testing, suggesting that these compounds might have a beneficial effect on oral health care. PMID- 26538800 TI - TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients. AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. METHODS: Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP expressing than in non-expressing tumors. The prognosis of patients with TSLP positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. CONCLUSION: TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. PMID- 26538801 TI - Multiple Skin Cancers in a Renal Transplant Recipient: A Patient Report with Analyses of Human Papillomavirus and Human Polyomavirus Infection. AB - Skin cancer is an important complication in renal transplant recipients. Associations of transplant-related skin tumor with ultraviolet radiation, age at transplantation, type of immunosuppressant drug administered, and viral infection have been reported; however, the details remain unclear. We report a 61-year-old man who had underwent renal transplantation at 38 years of age and developed multiple skin tumors or squamous cell carcinomas (SCCs). Polymerase chain reaction (PCR) analyses of the patient's 12 tumors for viral DNAs of cutaneous or mucosal human papillomavirus (HPV) and 6 human polyomaviruses (MCPyV, trichodysplasia spinulosa-associated, BK, JC, KI and WU polyomaviruses) only detected cutaneous HPV-DNA in only 5 of the tumors; no other viruses were detected. Real-time PCR showed high loads of cutaneous HPV in 3 SCCs and very low loads of MCPyV in 9. Immunohistochemistry revealed no tumor cell expression for MCPyV-large T-antigen or mucosal HPV. Our report not only reconfirmed the association of cutaneous HPV5 with skin cancer in renal transplant recipients in previous studies but also showed no relevant association of 6 human polyomaviruses and mucosal HPV with skin tumors. PMID- 26538803 TI - Rational general solutions of planar rational systems of autonomous ODEs. AB - In this paper, we provide an algorithm to compute explicit rational solutions of a rational system of autonomous ordinary differential equations (ODEs) from its rational invariant algebraic curves. The method is based on the proper rational parametrization of these curves and the fact that by linear reparametrizations, we can find the rational solutions of the given system of ODEs. Moreover, if the system has a rational first integral, we can decide whether it has a rational general solution and compute it in the affirmative case. PMID- 26538802 TI - Race, Gender, and Conceptualizations of Fear. AB - This study used qualitative methods and quantitative statistical analyses to examine whether race and gender are associated with reasons for which adults perceive a situation or object as fearful. The sample consists of 197 African American and White adults (ages 18-85) recruited through a convenience sample and community sources in the Midwest. A cognitive interviewing instrument was utilized to examine respondents understanding of words and phrases from a mental health instrument. Using qualitative methods, free-response answers were content coded using 5 "fear-codes" (i.e., harm/danger, external locus of control, self perception, and past experience), developed by the researchers. Results from logistic regression analyses indicate that race significantly predicts usage of specific fear codes (p<.05). In addition, a race by gender interaction was found. PMID- 26538804 TI - Trading order for degree in creative telescoping. AB - We analyze the differential equations produced by the method of creative telescoping applied to a hyperexponential term in two variables. We show that equations of low order have high degree, and that higher order equations have lower degree. More precisely, we derive degree bounding formulas which allow to estimate the degree of the output equations from creative telescoping as a function of the order. As an application, we show how the knowledge of these formulas can be used to improve, at least in principle, the performance of creative telescoping implementations, and we deduce bounds on the asymptotic complexity of creative telescoping for hyperexponential terms. PMID- 26538805 TI - Design and Evaluation of a Robust PID Controller for a Fully Implantable Artificial Pancreas. AB - Treatment of type 1 diabetes mellitus could be greatly improved by applying a closed-loop control strategy to insulin delivery, also known as an artificial pancreas (AP). In this work, we outline the design of a fully implantable AP using intraperitoneal (IP) insulin delivery and glucose sensing. The design process utilizes the rapid glucose sensing and insulin action offered by the IP space to tune a PID controller with insulin feedback to provide safe and effective insulin delivery. The controller was tuned to meet robust performance and stability specifications. An anti-reset windup strategy was introduced to prevent dangerous undershoot toward hypoglycemia after a large meal disturbance. The final controller design achieved 78% of time within the tight glycemic range of 80-140 mg/dL, with no time spent in hypoglycemia. The next step is to test this controller design in an animal model to evaluate the in vivo performance. PMID- 26538806 TI - National Human Trafficking Initiatives: Dimensions of Policy Diffusion. AB - The implementation of criminal law involves formal law enforcement, education and public outreach aimed at preventing criminal activity, and providing services for victims. Historically, quantitative research on global trends has tended to focus on a single policy dimension, potentially masking the unique factors that affect the diffusion of each policy dimension independently. Using an ordered-probit model to analyze new human trafficking policy data on national prosecution, prevention, and victim-protection efforts, we find that global ties and domestic interest groups matter more in areas where international law is less defined. While prosecution, officially mandated by the Trafficking Protocol, was relatively impervious to global ties and domestic interest groups, both trafficking prevention and victim protection were associated with these factors. Our findings also suggest that fear of repercussions is not a major driver of state actions to combat trafficking-neither ratification of the Trafficking Protocol nor levels of United States aid were associated with greater implementation of anti-trafficking measures. PMID- 26538807 TI - Characteristics of structures and lesions of the eye in laboratory animals used in toxicity studies. AB - Histopathology of the eye is an essential part of ocular toxicity evaluation. There are structural variations of the eye among several laboratory animals commonly used in toxicity studies, and many cases of ocular lesions in these animals are related to anatomical and physiological characteristics of the eye. Since albino rats have no melanin in the eye, findings of the fundus can be observed clearly by ophthalmoscopy. Retinal atrophy is observed as a hyper reflective lesion in the fundus and is usually observed as degeneration of the retina in histopathology. Albino rats are sensitive to light, and light-induced retinal degeneration is commonly observed because there is no melanin in the eye. Therefore, it is important to differentiate the causes of retinal degeneration because the lesion occurs spontaneously and is induced by several drugs or by lighting. In dogs, the tapetum lucidum, a multilayered reflective tissue of the choroid, is one of unique structures of the eye. Since tapetal cells contain reflecting crystals in which a high level of zinc has been demonstrated chemically, drug-induced tapetum degeneration is possibly related to zinc chelation. The eye of the monkey has a macula similar to that of humans. The macula consists only of cones with a high density, and light falls directly on the macula that plays an important role in visual acuity. Macular degeneration occurring in monkeys resembles histopathologically that of humans. Hence, the eye of the monkey is a suitable model to investigate macular degeneration and to assess drug-induced macular lesions. PMID- 26538808 TI - Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats. AB - Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22. Necropsy of all rats was performed at week 23, and livers and kidneys were examined histopathologically. Incidences of hepatocellular adenomas, and those of combined hepatocellular adenomas and carcinomas were significantly elevated in rats given 1,000 mg/kg/day ETBE, but not 100-500 mg/kg/day ETBE, and there was a significant increase in the average numbers of lesions. No significant differences in incidences and average numbers of renal tubule neoplasms were found in rats administered 100-1,000 mg/kg/day ETBE. However, the average numbers of atypical tubule hyperplasias, considered to be preneoplastic lesions, were significantly increased in rats given ETBE at 1,000 mg/kg/day, but not in rats given 500 mg/kg/day or lower doses. Thus, these results imply that ETBE has hepatic and renal tumor-promoting activities that affect EHEN-induced carcinogenesis in male rats, and the no-observed-effect level is 500 mg/kg/day under the present experimental conditions. PMID- 26538809 TI - Dietary curcumin supplementation attenuates 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) neurotoxicity in C57BL mice. AB - Studies in vivo and in vitro suggest that curcumin is a neuroprotective agent. Experiments were conducted to determine whether dietary supplementation with curcumin has neuroprotective effects in a mouse model of Parkinson's disease (PD). Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly induced the loss of dopaminergic cells in the substantia nigra and deletion of dopamine in the striatum, which was attenuated by long-term (7 weeks) dietary supplementation with curcumin at a concentration of 0.5% or 2.0% (w/w). Although curcumin did not prevent the MPTP-induced apoptosis of neuroblasts in the subventricular zone (SVZ), it promoted the regeneration of neuroblasts in the anterior part of the SVZ (SVZa) at 3 days after MPTP treatment. Furthermore, curcumin enhanced the MPTP-induced activation of microglia and astrocytes in the striatum and increased the expression of glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta1 (TGFbeta1) in the striatum and SVZ. GDNF and TGFbeta1 are thought to play an important role in protecting neurons from injury in the central and peripheral nervous systems. These results suggest that long-term administration of curcumin blocks the neurotoxicity of MPTP in the nigrostriatal dopaminergic system of the mouse and that the neuroprotective effect might be correlated with the increased expression of GDNF and TGFbeta1. Curcumin may be effective in preventing or slowing the progression of PD. PMID- 26538810 TI - Predictive modes of action of pesticides in uterine adenocarcinoma development in rats. AB - Endometrial adenocarcinoma in the uterine corpus is a malignant cancer that occurs in menopausal women and aged rodents. Because of the similarities in pathogenesis and morphology of endometrial adenocarcinoma in rodents and humans, prediction of the modes of action (MOA) in uterine carcinogenesis is important for extrapolation of rodent data to humans. Three MOAs have been accepted as major pathways for uterine carcinogenesis in rodents: 1) estrogenic activity, 2) increased serum 17beta-estradiiol (E2) to progesterone (P4) ratio and 3) modulation of estrogen metabolism to produce 4-hydroxyestradiol via P450 induction. Inhibition of estrogen excretion and increased aromatase in situ in the tumor are also a potential pathway. Here, chemicals showing uterine carcinogenicity were chosen from approximately 300 pesticides evaluated in Japan within the past decade, and their mechanisms were predicted using parameters from mechanistic and toxicity studies. Seven pesticides increased uterine tumor formation in rats, and the pathways of 4 pesticides could be predicted based on various mechanistic studies. The MOAs of cyenopyrafen and benthiavalicarb isopropyl were predicted to be modulation of estrogen metabolism, while those of pyriminobac-methyl and spirodiclofen were predicted to be increased E2 to P4 ratio. The driven pathways of metazosulfuron and isopyrazam could not be predicted using several mechanistic studies. No mechanistic studies have been reported for sedaxane, which has a chemical structure and toxicological profile similar to isopyrazam. Our results indicated that appropriate mechanistic studies are useful for mechanism prediction in risk assessment. From this analysis, a flowchart showing a decision tree for predictive MOAs in uterine carcinogenesis was proposed. PMID- 26538811 TI - Application of a compact magnetic resonance imaging system for toxicologic pathology: evaluation of lithium-pilocarpine-induced rat brain lesions. AB - Magnetic resonance imaging (MRI) is a useful noninvasive tool used to detect lesions in clinical and veterinary medicine. The present study evaluated the suitability of a new easy-to-use compact MRI platform (M2 permanent magnet system, Aspect Imaging, Shoham, Israel) for assisting with preclinical toxicologic pathology examination of lesions in the rat brain. In order to induce brain lesions, male Sprague-Dawley rats were treated once with lithium chloride (127 mg/kg, intraperitoneal [i.p.]) followed by pilocarpine (30 mg/kg, i.p.). One week after dosing, the perfused, fixed brains were collected, analyzed by the MRI system and examined histopathologically. MRI of the brain of treated rats revealed areas of high T1 and middle to low T2 signals, when compared with the controls, in the piriform cortex, lateral thalamic nucleus, posterior paraventricular thalamic nucleus and posterior hypothalamic nucleus of the cerebrum. The altered MRI signal areas were consistent with well-circumscribed foci of neuronal cell degeneration/necrosis accompanied by glial cell proliferation. The present data demonstrated that quick analysis of fixed organs by the MRI system can detect the presence and location of toxicologic lesions and provide useful temporal information for selection of appropriate sections for histopathologic examination before routine slide preparation, especially in complex and functionally heterogeneous organs such as the brain. PMID- 26538812 TI - Vitelline cyst in the rat ileum. AB - Congenital vitelline duct anomalies other than Meckel's diverticulum are rare in animals. A cyst of approximately 8 mm in diameter was observed on the antimesenteric surface of the ileal serosa in a 10-week-old female Crl:CD(SD) rat. Microscopically, the cyst closely resembled the ileum, but it did not communicate with the ileal lumen. We diagnosed this case as a vitelline cyst derived from the vitelline duct based on the location where it developed and its histological behavior. In rats, only Meckel's diverticulum has been reported with a congenital anomaly of the vitelline duct, and no other spontaneous anomalies including a vitelline cyst have been reported. This case may be the first report concerning a vitelline cyst in the rat ileum. PMID- 26538813 TI - Lipomatosis of the canine parotid gland: case report with a literature review. AB - In this report, we describe a case of lipomatosis in the left parotid gland of an eight-year-old female Shetland sheepdog and review the relevant literature. Preoperative diagnosis of lipomatosis with Tru-Cut biopsy presented difficulties in this case. The postoperative diagnosis was based on the gross appearance of a non-infiltrative, circumscribed swollen mass in the parotid gland and the histological appearance of normal adipocytes that infiltrated into the parotid gland without involving surrounding structures. Additionally, flotation of the whole parotid gland in formalin solution together with well-maintained residual lobulation and a well-maintained configuration on the cut surface were identified as subsidiary characteristics of lipomatosis of the parotid gland. Lipomatosis of the parotid gland has been rarely reported in dogs and is a poorly understood condition. PMID- 26538814 TI - A case of spontaneous myocardial necrosis and cerebral ischemic lesions in a laboratory beagle dog. AB - A beagle dog treated with saline as a control animal in a preclinical study was euthanized due to sudden systemic deterioration. On histopathological examination, contraction band necrosis of myocardial cells was observed widely in the left ventricular wall, including the papillary muscle and apex, and observed slightly in the ventricular septum and left atrium. In the brain, necrosis was observed in neurons and glia of the cerebral cortex, hippocampal pyramidal cells, glial cells of the rostral commissure and Purkinje cells of the cerebellar vermis. It is highly probable that the marked systemic deterioration was caused by cardiac dysfunction due to the spontaneous contraction band necrosis of the myocardial cells, although the pathogenesis of the myocardial lesions remains unclear. Given the distribution of neuronal necrosis in the brain, it is likely that these lesions resulted from the ischemia responsible for acute cardiac failure. PMID- 26538815 TI - Spontaneous early-onset glomerulonephritis in a 8-week-old male Crj:CD1 (ICR) mouse. AB - Glomerular lesions including membranoproliferative glomerulonephritis occur spontaneously in aged mice, but they are rare in young animals. In our laboratory, spontaneous glomerulonephritis was observed in an 8-week-old male Crj:CD1 (ICR) mouse. Macroscopically, the bilateral kidneys were discolored, but no edema or ascites was observed. Glomerular lesions were characterized by a thickening of capillary walls, a double-contoured basement membrane and mesangial expansion due to increased amounts of matrix. Ultrastructurally, mesangial interposition in the capillary wall and subendothelial deposition of basement membrane-like material were observed. No evidence of immune complex deposition or amyloid was found. On the basis of the observed clinical pathology and histopathology, a secondary form of glomerular lesion was excluded. The glomerular lesion was compatible with glomerulonephritis in a young Crj:CD1 (ICR) mouse. PMID- 26538816 TI - Histopathological evaluation of the ocular-irritation potential of shampoos, make up removers and cleansing foams in the bovine corneal opacity and permeability assay. AB - The bovine corneal opacity and permeability (BCOP) assay is an alternative method to the in vivo Draize eye test in rabbits for evaluating eye irritation in vitro. Here, we compared the numerical results of the BCOP assay with the corresponding histopathology for three different corneas for each test substance, including commercially available shampoos, make-up removers and cleansing foams that contained surfactants and other ingredients. The histopathological score was defined based on the severity of lesions in the corneal epithelium. The histopathological findings and scores of the three sections for each test substance were comparable. The in vitro irritancy score (IVIS) generally corresponds to the corneal irritant potential of the test substances assigned on the basis of the histopathological findings in this study. In the present study, we characterized the histopathology of the corneal epithelium and stroma and especially showed that the corneal epithelial injury caused by test substances might be important in assessment of test substances that are mild eye irritants (category 2B) as classified by the United Nations (UN) Globally Harmonized System of Classification and Labelling of Chemicals (GHS), as corneal lesions suggestive of classification into category 2B were localized on the border between the corneal epithelium and stroma, which contained cell elements related to assessment of prognosis of an in vivo eye injury. Histopathological assessment might be useful in predicting in vivo ocular irritation, particularly for test substances with an IVIS >3.1 but <=25 that are classified as mild irritants (category 2B) according to the UN GHS. PMID- 26538817 TI - Sex Differences in Neuropsychiatric Symptoms of Alzheimer's Disease: The Modifying Effect of Apolipoprotein E epsilon4 Status. AB - Sex differences in neuropsychiatric symptoms of Alzheimer's disease (AD) have been demonstrated in previous studies, and apolipoprotein E (ApoE) epsilon4 status influences psychiatric manifestations of AD. However, whether ApoE epsilon4 status modifies the sex differences in neuropsychiatric symptoms of AD is still unclear. In this study, sex differences in neuropsychiatric abnormalities were stratified and analyzed by ApoE epsilon4 status in mild AD and moderate to severe AD separately. The Clinical Dementia Rating (CDR) scale and the Neuropsychiatric Inventory (NPI) were used to assess dementia severity and neuropsychiatric symptoms. No sex differences were found in mild AD. In moderate to severe AD, among epsilon4 positive individuals, disinhibition was significantly more prevalent (8.0% in men versus 43.2% in women, p = 0.003) and severer (p = 0.003) in female patients. The frequency (16.0% in men versus 51.4% in women, p = 0.005) and score (p = 0.004) of irritability were of borderline significance after strict Bonferroni correction. In conclusion, this study supported the modifying effect of ApoE epsilon4 status on sex differences in neuropsychiatric symptoms of AD, and this modifying effect was pronounced in moderate to severe stage of AD. The interaction between gender and ApoE epsilon4 status should be considered in studies on neuropsychiatric symptoms of AD. PMID- 26538818 TI - A Disproportionate Burden of Care: Gender Differences in Mental Health, Health Related Quality of Life, and Social Support in Mexican Multiple Sclerosis Caregivers. AB - BACKGROUND: Multiple sclerosis (MS) rates in Latin America are increasing, and caregivers there experience reduced mental and physical health. Based on rigid gender roles in Latin America, women more often assume caregiving duties, yet the differential impact on women of these duties is unknown. METHODS: This study examined gender differences in mental health (Patient Health Questionnaire-9, Satisfaction with Life Scale, Rosenberg Self-Esteem Scale, State-Trait Anxiety Inventory, and Zarit Burden Inventory), health-related quality of life (HRQOL; Short Form-36), and social support (Interpersonal Support Evaluation List-12) in 81 (66.7% women) Mexican MS caregivers. RESULTS: As compared to men caregivers, women had lower mental health (p = 0.006), HRQOL (p < 0.001), and social support (p < 0.001). This was partially explained by women caregivers providing care for nearly twice as many hours/week as men (79.28 versus 48.48, p = 0.018) and for nearly three times as many months (66.31 versus 24.30, p = 0.002). CONCLUSIONS: Because gender roles in Latin America influence women to assume more substantial caregiving duties, MS caregiver interventions in Latin America-particularly for women caregivers-should address the influence of gender-role conformity on care and psychosocial functioning. PMID- 26538819 TI - Relationship between Postmenopausal Estrogen Deficiency and Aneurysmal Subarachnoid Hemorrhage. AB - Aneurysmal subarachnoid hemorrhage (SAH) is one of the most severe forms of stroke, which results from the rupture of a cerebral aneurysm. SAH is the only type of stroke with a female predominance, suggesting that reproductive factors may play a significant role in the etiology. Estrogen has important effects on vascular physiology and pathophysiology of cerebral aneurysm and SAH and, thus, potential therapeutic implications. There have been growing bodies of epidemiological and experimental studies which support the hypothesis of a significant relationship between estrogen deficiency and cerebral aneurysm formation with subsequent SAH. This hypothesis is the focus of this review as well as possible pathology-based therapeutics with regard to aspects of molecular pathophysiology, especially related to women's health. PMID- 26538820 TI - Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation. AB - Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation. PMID- 26538823 TI - Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development. AB - Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-alpha. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development. PMID- 26538821 TI - Dental Pulp Defence and Repair Mechanisms in Dental Caries. AB - Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo. PMID- 26538822 TI - Marine Diterpenoids as Potential Anti-Inflammatory Agents. AB - The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-kappaB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID- 26538824 TI - Relationship among Short and Long Term of Hypoinsulinemia-Hyperglycemia, Dermatophytosis, and Immunobiology of Mononuclear Phagocytes. AB - Dermatophytes are fungi responsible for causing superficial infections. In patients with diabetes mellitus (DM), dermatophytosis is usually more severe and recurrent. In the present study, we aimed to investigate the influence of short and long term hypoinsulinemia-hyperglycemia (HH) during experimental infection by Trichophyton mentagrophytes as well as alterations in the mononuclear phagocytes. Our results showed two distinct profiles of fungal outcome and immune response. Short term HH induced a discrete impaired proinflammatory response by peritoneal adherent cells (PAC) and a delayed fungal clearance. Moreover, long term HH mice showed low and persistent fungal load and a marked reduction in the production of TNF-alpha by PAC. Furthermore, while the inoculation of TM in non-HH mice triggered high influx of Gr1(+) monocytes into the peripheral blood, long term HH mice showed low percentage of these cells. Thus, our results demonstrate that the time of exposure of HH interferes with the TM infection outcome as well as the immunobiology of mononuclear phagocytes, including fresh monocyte recruitment from bone marrow and PAC activity. PMID- 26538825 TI - Is Pulp Inflammation a Prerequisite for Pulp Healing and Regeneration? AB - The importance of inflammation has been underestimated in pulpal healing, and in the past, it has been considered only as an undesirable effect. Associated with moderate inflammation, necrosis includes pyroptosis, apoptosis, and nemosis. There are now evidences that inflammation is a prerequisite for pulp healing, with series of events ahead of regeneration. Immunocompetent cells are recruited in the apical part. They slide along the root and migrate toward the crown. Due to the high alkalinity of the capping agent, pulp cells display mild inflammation, proliferate, and increase in number and size and initiate mineralization. Pulp fibroblasts become odontoblast-like cells producing type I collagen, alkaline phosphatase, and SPARC/osteonectin. Molecules of the SIBLING family, matrix metalloproteinases, and vascular and nerve mediators are also implicated in the formation of a reparative dentinal bridge, osteo/orthodentin closing the pulp exposure. Beneath a calciotraumatic line, a thin layer identified as reactionary dentin underlines the periphery of the pulp chamber. Inflammatory and/or noninflammatory processes contribute to produce a reparative dentinal bridge closing the pulp exposure, with minute canaliculi and large tunnel defects. Depending on the form and severity of the inflammatory and noninflammatory processes, and according to the capping agent, pulp reactions are induced specifically. PMID- 26538826 TI - Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage. AB - Garcinia Linn. plants having rich natural xanthones and benzophenones with anti inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8 isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNgamma-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-alpha. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE's capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-kappaB) as well as NF-kappaB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases. PMID- 26538827 TI - Downregulation of mPGES-1 Expression via EGR1 Plays an Important Role in Inhibition of Caffeine on PGE2 Synthesis of HBx(+) Hepatocytes. AB - We investigated the mechanism of caffeine in influencing HBx(+) hepatocytes to synthesize PGE2. The inhibitory effect of caffeine on hepatocyte proliferation increased with increasing caffeine concentrations (200-800 MUM) and treatment times (1-7 days), which was first observed at the second test time point (caffeine treatment for 4 days). The inhibition of caffeine on the growth of HL7702-HBx and HepG2-HBx cells was most obvious at 800 MUM caffeine and at caffeine treatment for 7 days. The PGE2 secretion and the expression of mPGES-1 and EGR1 were downregulated, whereas PPARgamma expression was upregulated. The mPGES-1 promoter activity of HBx(+) hepatocytes decreased more significantly than that of HBx(-) hepatocytes. Moreover, the expression of EGR1 and PPARgamma changed more significantly in HBx(+) hepatocytes cultured for 12 to 24 hours in the presence of 5 mM caffeine. This limited success may be attributed to caffeine releasing the binding of HBx and PPARgamma and furthermore affecting the mPGES-1 expression by EGR1 in HBx(+) hepatocytes. The results indicate that caffeine could effectively reduce PGE2 synthesis in HBx(+) hepatocytes by specifically blocking the PPARgamma-EGR1-mPGES-1 pathway, thereby providing a new evidence of molecular biology for the hypothesis that drinking coffee is beneficial to HBV infected patients. PMID- 26538829 TI - Urinary Malondialdehyde Is Associated with Visceral Abdominal Obesity in Middle Aged Men. AB - The purpose of the present study was to investigate multiple anthropometric parameters used to evaluate obesity, particularly visceral abdominal fat area, and various metabolic parameters including malondialdehyde (MDA) as an oxidative stress marker. We evaluated various measures of obesity, including body mass index (BMI), waist circumference (WC), sagittal abdominal diameter, fat percentages using dual-energy X-ray absorptiometry, visceral fat area (VFA), subcutaneous fat area, multiple biomarkers related to metabolic disease, and urinary MDA, in 73 asymptomatic middle-aged men who were not severely obese. We examined relationships between multiple measures of obesity, metabolic markers, and urinary MDA levels and evaluated associations between VFA and urinary MDA. In the visceral obesity group, gamma-glutamyl transferase (GGT), uric acid, and urinary MDA levels were significantly higher than in the nonvisceral obesity group (P = 0.008, P = 0.002, and P = 0.018). Urinary MDA (r = 0.357, P = 0.002) and uric acid (r = 0.263, P = 0.027) levels were only significantly positively correlated with VFA among measures of obesity. Urinary MDA, serum GGT, and serum CRP were significantly positively associated with VFA (P = 0.001, P = 0.046, and P = 0.023, resp.), even after adjusting for BMI and WC. PMID- 26538830 TI - Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm. AB - Our understanding of inflammation's role in the pathogenesis of myeloproliferative neoplasm (MPN) is evolving. The impact of chronic inflammation, a characteristic feature of MPN, likely goes far beyond its role as a driver of constitutional symptoms. An inflammatory response to the neoplastic clone may be responsible for some pathologic aspects of MPN. Moreover, JAK2V617F mutated hematopoietic stem and progenitor cells are resistant to inflammation, and this gives the neoplastic clone a selective advantage allowing for its clonal expansion. Because inflammation plays a central role in MPN inflammation is a logical therapeutic target in MPN. PMID- 26538831 TI - Influence of Malondialdehyde and Matrix Metalloproteinase-9 on Progression of Carotid Atherosclerosis in Chronic Renal Disease with Cardiometabolic Syndrome. AB - Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase 9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS. PMID- 26538828 TI - Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma. AB - Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma. PMID- 26538834 TI - Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis. AB - Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra articularly injected with CDCA (10 mg/kg or 50 mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. CDCA also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin 1beta (IL-1beta), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight CDCA might be a potential therapeutic agent for OA. PMID- 26538835 TI - Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice. AB - Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80(+)/CD80(+) and F4/80(+)/CD86(+) cells to the bronchoalveolar space, induced higher production of IFN-gamma, IL-6, MIP-1alpha, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection. PMID- 26538833 TI - The Role of Reactive Oxygen Species in Myelofibrosis and Related Neoplasms. AB - Reactive oxygen species (ROS) have been implicated in a wide variety of disorders ranging between traumatic, infectious, inflammatory, and malignant diseases. ROS are involved in inflammation-induced oxidative damage to cellular components including regulatory proteins and DNA. Furthermore, ROS have a major role in carcinogenesis and disease progression in the myeloproliferative neoplasms (MPNs), where the malignant clone itself produces excess of ROS thereby creating a vicious self-perpetuating circle in which ROS activate proinflammatory pathways (NF-kappaB) which in turn create more ROS. Targeting ROS may be a therapeutic option, which could possibly prevent genomic instability and ultimately myelofibrotic and leukemic transformation. In regard to the potent efficacy of the ROS-scavenger N-acetyl-cysteine (NAC) in decreasing ROS levels, it is intriguing to consider if NAC treatment might benefit patients with MPN. The encouraging results from studies in cystic fibrosis, systemic lupus erythematosus, and chronic obstructive pulmonary disease warrant such studies. In addition, the antioxidative potential of the widely used agents, interferon alpha2, statins, and JAK inhibitors, should be investigated as well. A combinatorial approach using old agents with anticancer properties together with novel JAK1/2 inhibitors may open a new era for patients with MPNs, the outlook not only being "minimal residual disease" and potential cure but also a marked improvement in inflammation-mediated comorbidities. PMID- 26538836 TI - Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts. AB - Osteoporosis is one of the most common bone diseases, which is characterized by a systemic impairment of bone mass and fragility fractures. Age-related oxidative stress is highly associated with impaired osteoblastic dysfunctions and subsequent osteoporosis. In osteoblasts (bone formation cells), reactive oxygen species (ROS) are continuously generated and further cause lipid peroxidation, protein damage, and DNA lesions, leading to osteoblastic dysfunctions, dysdifferentiations, and apoptosis. Although much progress has been made, the mechanism responsible for oxidative stress induced cellular alternations and osteoblastic toxicity is still not fully elucidated. Here, we demonstrate that protein phosphatase 2A (PP2A), a major protein phosphatase in mammalian cells, mediates oxidative stress induced apoptosis in osteoblasts. Our results showed that lipid peroxidation products (4-HNE) may induce dramatic oxidative stress, inflammatory reactions, and apoptosis in osteoblasts. These oxidative stress responses may ectopically activate PP2A phosphatase activity, which may be mediated by inactivation of AKT/mTOR pathway. Moreover, inhibition of PP2A activity by okadaic acid might partly prevent osteoblastic apoptosis under oxidative conditions. These findings may reveal a novel mechanism to clarify the role of oxidative stress for osteoblastic apoptosis and provide new possibilities for the treatment of related bone diseases, such as osteoporosis. PMID- 26538832 TI - Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases. AB - Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases. PMID- 26538837 TI - Natural Products: Insights into Leishmaniasis Inflammatory Response. AB - Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID- 26538838 TI - Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study. AB - PURPOSE: This study quantified the expression of substance P (SP), calcitonin gene-related peptide (CGRP), beta-endorphins (beta-End), and methionine enkephalin (Met-Enk) in human dental pulp following orthodontic intrusion. METHODS: Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons) were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg), which would undergo controlled intrusive force for seven days, and the control group (CTRg), which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA). RESULTS: All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. CONCLUSIONS: SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain. PMID- 26538841 TI - Multiples sclerosis in India. PMID- 26538839 TI - Treatment of Cancer Pain by Targeting Cytokines. AB - Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom. PMID- 26538842 TI - Neuromyelitis optica spectrum disorders: An update. AB - Recent advances in the understanding of neuromyelitis optica spectrum of disorders (NMOSD) have expanded. Diagnostic criteria have changed over the years. The clinical spectrum of disease manifestations are now understood to include sites outside the spinal cord and optic nerve. A variety of autoimmune diseases may coexist with this disorder. Non neurological manifestations have been recently reported. Novel biomarkers other than aquoporin 4 Immunoglobulin G (anti AQP4-IgG) have been discovered which may have clinical relevance. In particul myelin associated oligoglycoprotein antibody (MOG-Ab) associated NMOSD may be relatively benign. This update describes some of these new findings highlighting the clinical manifestations, biomarkers associated with the disease and magnetic resonance imaging characteristics of brain and spinal cord. PMID- 26538840 TI - Haemodynamic response associated with both ictal and interictal epileptiform activity using simultaneous video electroencephalography/near infrared spectroscopy in a within-subject study. AB - This paper reports the findings from a pilot study of four patients with medically refractory epilepsy undergoing pre-surgical evaluation with ages ranging from 5 to 17 years. Video electroencephalography recordings and data from a near infrared spectroscopy cerebral/somatic oximeter were gathered and related to electrographic seizure onset and offset as determined by a paediatric epileptologist. All four patients showed haemodynamic changes associated with epileptiform activities. The increased blood flow clearly coincided with epileptiform activity and continued to increase as the epileptiform activity built up. Regional cerebral oxygen saturation increased in the epileptogenic focus, perhaps due to loss of cerebrovascular autoregulation. These findings reinforce that near infrared spectroscopy can potentially be used in a wide spectrum of patients with epilepsy regardless of the underlying brain pathology. PMID- 26538843 TI - Therapy of NMO spectrum disorders. AB - Neuromyelitis optica (NMO) is an autoimmune demyelinating condition of the central nervous system often associated with aquaporin-4 (AQP4) autoantibodies manifesting as severe optic neuritis and long segment myelitis with tendency to relapse. Seronegative patients and who do not meet the NMO criteria are classified as having NMO Spectrum Disorder (NMOSD), but are treated identically to clinically definite NMO. Acute relapse is treated with intravenous methylprednisolone for 5 days with or without subsequent treatment with plasma exchange (PE). This must be followed by oral steroid to prevent rebound worsening and further relapse. For relapse prevention, immunosuppressive agents that have been found to be effective are azathioprine, rituximab, mycophenolate mofetil, methotrexate, and mitoxantrone; although none of which have been validated in randomized, controlled trial. Some patients do relapse with monotherapy, and switching to more effective agent or use of combination therapy is beneficial in such situation. There is no consensus about the duration of preventive therapy, but generally 2-3 years of relapse-free period is considered the minimum, taking into account the risks of long-term toxicity of these agents. PMID- 26538844 TI - Multiple sclerosis in India: An overview. AB - Multiple sclerosis (MS) is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI). The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS) was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica - a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost. PMID- 26538845 TI - Systematic imaging review: Multiple Sclerosis. AB - Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system characterised by immune-mediated demyelination, and is a leading cause of neurological disability worldwide. It has a wide spectrum of clinical presentations which overlap with other neurological conditions many times. Further, the radiological array of findings in MS can also be confused for multiple other conditions, leading to the need to look for the more typical findings, and interpret these in close conjunction with the clinical picture including temporal evolution. This review aims to revisit the MRI findings in MS, including recent innovations in imaging, and to help distinguish MS from its mimics. PMID- 26538846 TI - Newer therapies for multiple sclerosis. AB - The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an "escalation" or "induction" approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects. PMID- 26538848 TI - Rehabilitation of multiple sclerosis patients in India. AB - Multiple sclerosis (MS) is a chronic progressive disease which is one of the leading causes of handicap in young subjects. The large range of symptoms associated with MS lead to continuing decline in neurologic status and quality of life. The coexistence of physical and cognitive impairments, together with the imprevisible evolution of the disease makes MS rehabilitation very challenging. The main objective of rehabilitation is, therefore, to ease the burden of symptoms by improving self-performance and independence. Inpatient, outpatient and Home rehabilitation with multidisciplinary team has been shown to be beneficial in improving disability. Individualized programs elaborated by a multidisciplinary team of experts are the key to success of rehabilitation. Family plays a big role and Family Based Rehabilitation will be important in long term rehab program in MS. PMID- 26538847 TI - Symptomatic management in multiple sclerosis. AB - Multiple sclerosis (MS) is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS) and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment. PMID- 26538849 TI - Acquired demyelinating disorders of central nervous system: A pediatric cohort. AB - OBJECTIVE: This is a retrospective chart review of consecutive children with acquired demyelinating disorders presenting to a north Indian tertiary care hospital over 4 years. The aim of this review is to describe all the patients (with single event as well as those with recurrences) with detailed description of those who recurred. MATERIALS AND METHODS: Overall 35 cases were reviewed and their clinical presentations, diagnosis, management, and follow-up are being presented. RESULTS: Out of 35 cases, 24 did not show any recurrences (seven acute disseminated encephalomyelitis (ADEM) and 17 clinically isolated syndromes). Amongst the 11 patients with recurrent demyelination, majority were multiple sclerosis (8/11, 72.7%) followed by neuromyelitis optica (NMO; 2/11), and multiphasic ADEM (1/11). The median disease duration and follow-up since onset for those with recurrent episodes is 4 years (2.5-4.5 years). Steroids caused significant improvement in acute episodes of demyelination. However, recurrent demyelinating disorders like multiple sclerosis and NMO required long-term immunomodulation. Azathioprine currently is the most favored long-term immunomodulator used in NMO. Interferon-beta and glatiramer acetate are currently recommended for multiple sclerosis. However, azathioprine may be a suitable alternative in a resource-limited setting. CONCLUSION: The consensus definitions for these groups of disorders need further validation in the pediatric age group. Studies with larger population size are required to characterize features that predict future recurrences. PMID- 26538850 TI - Multisystem involvement in neuromyelitis optica. AB - We describe a case of pediatric neuromyelitis optica (NMO) with muscle and lung involvement in addition to central nervous system disease. Our patient initially presented with features of area postrema syndrome, then subsequently with optic neuritis. The patient also had recurrent hyperCKemia that responded to corticosteroids. Finally, axillary and hilar adenopathy with pulmonary consolidation were noted as well and responded to immunomodulation. Our case highlights multisystem involvement in NMO including non-infectious pulmonary findings which have not been described in the pediatric population previously. PMID- 26538852 TI - From the Editor's desk. PMID- 26538851 TI - Epidemiology and genetic aspects of multiple sclerosis in India. AB - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a complex pathophysiology. Considered a rare disease in India in the past, studies over time suggest an increase in subjects with MS in India, although the observations are limited by the lack of formally conducted epidemiological studies and the absence of a nationwide registry. The current World Health Organization (WHO) Multiple Sclerosis International Federation (MSIF) "Atlas of MS" 2013 estimates a prevalence rate of 5-20 per 100,000, which also seems an underestimate. Although there have been reports of phenotypic differences between MS in Indians and the Western counterparts, recent studies report a reasonable similarity in disease types and characteristics. A few studies on the genetics of MS have been reported, including human leukocyte antigen (HLA) associations and non-major histopathology complex (MHC) disease loci. The current review discusses the pivotal studies of the past, newer observations on MS from India, and the need for a national registry. PMID- 26538853 TI - Endometrial receptivity array: Clinical application. AB - Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID- 26538854 TI - Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach. AB - Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its "culture-bound" status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder. PMID- 26538855 TI - Dehydroepiandrosterone as an adjunct to gonadotropins in infertile Indian women with premature ovarian aging: A pilot study. AB - BACKGROUND: Dehydroepiandrosterone (DHEA) supplementation is a relatively recent development that augments ovarian responsiveness in patients with poor ovarian reserve and premature ovarian aging (POA). AIMS: To evaluate the efficacy of DHEA supplementation prior to gonadotropins for ovulation induction in women with POA. DESIGN: Prospective randomized controlled study. METHODS: Fifty infertile women with POA were randomized into two groups of 25 each. Group 1 received tablet DHEA 25 mg while group 2 received placebo thrice daily for 6 months. After 3 months, gonadotropin induction with intrauterine insemination was done. STATISTICAL ANALYSIS: Groups were compared using t-test and Mann-Whitney U-test as appropriate. Pre- and post-parameters were compared using t-test -paired and Wilcoxon signed-rank tests as appropriate. RESULTS: Of 50 patients, 62% (31/50) presented with primary and 38% (19/50) with secondary infertility. The mean age was 32.1 +/- 4.7 years. Serum antimullerian hormone levels (1.5 +/- 0.6-1.9 +/- 0.4 ng/ml vs. 1.4 +/- 0.5-1.5 +/- 0.6 ng/ml) and antral follicle count (3.2 +/- 1.0-9.3 +/- 3.1 vs. 3.3 +/- 1.1-3.4 +/- 1.4) improved significantly in DHEA group after 3 months. Serum follicular stimulating hormone and estradiol levels though showed significant intra-group improvement (16.9 +/- 5.5 mIU/ml to 14.7 +/- 6.2 mIU/ml and 86.6 +/- 57.5 pg/ml to 105.6 +/- 54.3 pg/ml, respectively) with DHEA, the inter group difference was not significant. Ovulation increased from 48% to 86.3% in DHEA group versus 44-66% in placebo group. Six women (24%) conceived after DHEA in comparison to none in the placebo group. CONCLUSIONS: DHEA supplementation may have a beneficial role as an adjunct to gonadotropins in the treatment of infertility with POA, but further evidence is required. PMID- 26538856 TI - Clomiphene based ovarian stimulation in a commercial donor program. AB - OBJECTIVE: This study was conducted to compare an extended clomiphene-based ovarian stimulation regimen with the conventional antagonist protocol in donor recipient cycles. MATERIALS AND METHODS: A total of 170 (N) donors were stimulated between January 2013 and December 2013. Conventional antagonist protocol (group I) was employed in (n1 = 31) cycles, and clomiphene was used in (n2 = 139) donor cycles (group II). 50 mg clomiphene was given simultaneously with gonadotropins from day 2 of the cycle until the day of trigger. The analysis was performed retrospectively for oocytes retrieved, fertilization rates, cycle cancelation, blastocyst formation, and pregnancy rates. The dosages, cost, and terminal E2 (estradiol) were also compared between the two groups. RESULTS: The donor age groups were comparable in both the groups. There were no unsuccessful egg retrievals with clomiphene. The pregnancy rate (positive beta human chorionic gonadotropin) was significantly higher in the clomiphene group (odds ratio: 2.453; P = 0.02). Similarly, fertilization rate was significantly higher in the clomiphene group (59.5/50.5, P = 0.04). Eggs retrieved were similar in both groups, but the terminal E2 was significantly higher in the clomiphene group (P = 0.001). Average gonadotropin used was also significantly lower in clomiphene group (P < 0.001). CONCLUSION: Clomiphene can effectively prevent luteinizing hormone surge and limit the dose of gonadotropins thus bringing down the costs and its negative impact on the endometrium and oocyte quality. PMID- 26538857 TI - Pregnancy outcome of assisted reproductive technology cycle in patients with hypogonadotropic hypogonadism. AB - CONTEXT: Ovulation induction in patients with hypogonadotropic hypogonadism (HH) is a challenge to the treating physician. The threshold for ovarian response in HH may differ substantially from that of normal patients. To reach that threshold levels of follicle stimulating hormone, in a step-up protocol longer duration of stimulation is required in some cases so as to prevent multiple pregnancy and to eliminate the risk of ovarian hyperstimulation syndrome. AIM: To evaluate the duration of stimulation, quality of oocytes, and embryo, and the pregnancy outcome in the assisted reproductive technology (ART) cycles in patients with HH. MATERIALS AND METHODS: Over the period of 4 years, we had 14 patients with HH in whom 21 cycles of ovulation induction were done. Of these 7 patients underwent oocyte retrieval and intracytoplasmic sperm injection (ICSI). We present a retrospective study of these 7 patients who underwent ART to evaluate the duration of stimulation, quality of oocytes and embryo, and the pregnancy outcome. RESULTS: In the study group on ovulation induction with gonadotropins, only one patient had the duration of stimulation of the standard 12 days, the remaining 6 patients took >=12 days to respond to stimulation (maxium being 54 days). Mean ET in these patients was 8.9 mm. Six patients had >70% good quality MII oocytes. One patient responded poorly and had only 2 good quality MII oocytes (50%). After ICSI procedure, resultant embryos were of grade 1 and 2 in all the patients irrespective of the duration of stimulation. Fertilization rate in these patients was 85% (except in one 50% fertilization rate), and the cumulative pregnancy rate was 68.6%. CONCLUSION: In the patients with HH the quality of oocytes and embryos, and the pregnancy rate is not affected even if the duration of stimulation is prolonged. PMID- 26538858 TI - Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle. AB - OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR). RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle. PMID- 26538859 TI - Microdeletion of Y chromosome as a cause of recurrent pregnancy loss. AB - CONTEXT: In majority of couples experiencing recurrent pregnancy loss (RPL), etiology is still unknown. Two genetic factors have been suggested to underlie miscarriage in a subset of patients, namely skewed X chromosome inactivation in females and Y chromosome microdeletions in their partners. In males, microdeletions of the Y chromosome are known to cause spermatogenetic failure and male infertility. AIMS: The aim of the study was to find out the role of Y chromosome microdeletion in male partners of couples experiencing RPL. SETTINGS AND DESIGN: University hospital and genetic laboratory. Prospective case-control study. SUBJECTS AND METHODS: 59 couples with a history of RPL and 20 fertile controls (FC) with no miscarriage were included in the study. The study subjects were divided into male partners of RPL couples with abnormal semen parameters (AS) (n = 8), and couples with normal semen parameters (NS) (n = 51). Fertile controls with normal semen parameters were (FC) (n = 20). Y chromosome microdeletion was performed on 40 male partners of RPL and 20 FC. STATISTICAL ANALYSIS USED: Chi-square test. P <0.05 were considered statistically significant. RESULTS: 13 of the 40 RPL cases showed deletion in three azoospermia factor loci on the long arm of Y chromosome. The P value was significant with Y chromosome microdeletion in RPL cases as compared to 20 FC where no Y chromosome microdeletion was present. CONCLUSIONS: Y chromosome microdeletion may be an important hidden cause of recurrent pregnancy miscarriage and can be offered to couples with the undiagnosed cause of miscarriage. PMID- 26538860 TI - Relevance of semen polymerase chain reaction positive for tuberculosis in asymptomatic men undergoing infertility evaluation. AB - OBJECTIVE: Male partners of infertile women with genital tuberculosis (TB) are often screened for genital TB. We aimed to evaluate the clinical significance of a positive screening semen polymerase chain reaction (PCR) for Mycobacterium tuberculosis test (TB-PCR) in asymptomatic men undergoing infertility evaluation and determine the need for a detailed investigation and treatment for TB. MATERIALS AND METHODS: Between March 2012 and January 2013, male partners of 15 infertile women with a diagnosis of genitourinary TB (GUTB) as the cause of infertility, tested positive either on semen PCR for TB (13 cases), or Mycobacterium Growth Indicator Tube-960 test (2 cases). These asymptomatic men underwent infertility evaluation along with evaluation for GUTB. Diagnosis of GUTB was based on standard clinical criteria, which included a high index of suspicion along with clinical, laboratory, and/or radiological evidence of GUTB. Men who had no clinical evidence of GUTB were followed up with clinical evaluation, semen analysis, and repeat semen PCR for TB after 6 months. RESULTS: Fourteen subjects consented for inclusion in the study. One had a history of pulmonary TB 20 years earlier. Another patient was found to have mediastinal lymphadenopathy (tubercular). All except one had a normal semen analysis. None of the patients met the standard clinical criteria for GUTB diagnosis. 8 patients followed up at 6 months with repeat semen analysis, which was similar to the baseline values and no clinical evidence of TB. INTERPRETATION AND CONCLUSIONS: Asymptomatic men with positive screening semen PCR for TB do not have clinical evidence of TB. Male partners of women with infertility and GUTB should not be screened if they have no symptoms. PMID- 26538861 TI - Empty follicle syndrome: Successful pregnancy following dual trigger. AB - Empty follicle syndrome (EFS) is an uncommon, but the frustrating complication of assisted reproductive technology with failure to obtain oocytes after an adequate ovarian response to stimulation. Most of the reported cases of EFS are drug related problems which are actually avoidable and do not represent any potential pathology and that the risk of genuine EFS (GEFS) is much smaller than was once thought. Our case is the first report of a pregnancy obtained after management of GEFS with dual trigger in a gonadotropin-releasing hormone (GnRH) antagonist cycle. In this report, we present a patient who underwent two oocyte retrievals, in which no oocytes were obtained. In the third in-vitro fertilization cycle, a dual trigger with the combination of GnRH agonist and human chorionic gonadotropin yielded 11 oocytes, which led to the transfer of 2 blastocysts resulting in a live birth. Changing the treatment protocol with dual trigger brought about a successful outcome. PMID- 26538862 TI - Successful fertilization and embryo development after spermatid injection: A hope for nonobstructive azoospermic patients. AB - Spermatids are the earliest male germ cells with haploid set of chromosomes. Spermatid injection was introduced in human assisted reproduction for the treatment of men with non-obstructive azoospermia. Spermatozoa can be recovered in half of patients with nonobstructive azoospermia. The use of spermatids for intracytoplasmic injection (ICSI) has been proposed for cases in which no spermatozoa can be retrieved. However, there are low pregnancy rates following ICSI using round spermatids from men with no elongated spermatids or spermatozoa in their testes. The in vitro culture of immature germ cells has been proposed as a means to improve this poor outcome. Oocyte activation rarely occurs when injected with a spermatid. Therefore, spermatid injection requires use of calcium ionophores for oocyte activation which is otherwise carried out by PLC zeta from mature sperms. This is the only option available for the nonobstructive azoospermic patients to have their own biological child. PMID- 26538863 TI - Pregnancy outcome with coexisting mole after intracytoplasmic sperm injection: A case series. AB - Partial/complete hydatidiform mole with coexisting fetus is a rare condition. Optimal management is a challenge that remains a dilemma since these pregnancies are associated with maternal as well as fetal complications including hemorrhage, preeclampsia, thromboembolic disease, intra uterine demise and increased risk of persistent trophoblastic disease. Here we report 2 cases of partial mole with live fetus after ICSI and a case of complete mole with coexisting fetus after ICSI in a turner mosaic that resulted in a live birth. PMID- 26538864 TI - Deep venous thrombosis in a patient undergoing In-vitro fertilization with oocyte donation. AB - Deep venous thrombosis (DVT) has been reported extensively following ovarian hyperstimulation syndrome during in-vitro fertilization (IVF). Pregnancy per se increases the risk of DVT due to a hypercoagulable state. The long-term use of hormone replacement therapy (HRT) is another critical factor associated with DVT in women. However, an association between the short-term use of HRT in oocyte donation (OD) cycles and DVT has not yet been reported. We present a case of 43 year-old woman who developed DVT after IVF-OD. DVT was diagnosed at 7 weeks of pregnancy and was managed with low-molecular-weight heparin. We suggest that even a short-term use of HRT should be considered a risk factor for DVT especially in the presence of additional risk factors such as obesity. The patient had an uneventful recovery and delivered three healthy though preterm babies. PMID- 26538865 TI - Sample size estimation and power analysis for clinical research studies: Retraction. AB - [This retracts the article on p. 7 in vol. 5, PMID: 22870008.]. PMID- 26538866 TI - Understanding implantation window, a crucial phenomenon: Retraction. AB - [This retracts the article on p. 2 in vol. 5, PMID: 22870007.]. PMID- 26538867 TI - Pulmonary Proteome and Protein Networks in Response to the Herbicide Paraquat in Rats. AB - Paraquat (PQ) has been one of the most widely used herbicides in the world. PQ, when ingested, is toxic to humans and may cause acute respiratory distress syndrome. To investigate molecular perturbation in lung tissues caused by PQ, Sprague Dawley male rats were fed with PQ at a dose of 25 mg/kg body weight for 20 times in four weeks. The effects of PQ on cellular processes and biological pathways were investigated by analyzing proteome in the lung tissues in comparison with the control. Among the detected proteins, 321 and 254 proteins were over-represented and under-represented, respectively, in the PQ-exposed rat lung tissues in comparison with the no PQ control. All over- and under represented proteins were subjected to Ingenuity Pathway Analysis to create 25 biological networks and 38 pathways of interacting protein clusters. Over represented proteins were involved in the C-jun-amino-terminal kinase pathway, caveolae-mediated endocytosis signaling, cardiovascular-cancer-respiratory pathway, regulation of clathrin-mediated endocytosis, non-small cell lung cancer signaling, pulmonary hypertension, glutamate receptor, immune response and angiogenesis. Under-represented proteins occurred in the p53 signaling pathway, mitogen-activated protein kinase signaling pathway, cartilage development and angiogenesis inhibition in the PQ-treated lungs. The results suggest that PQ may generate reactive oxygen species, impair the MAPK/p53 signaling pathway, activate angiogenesis and depress apoptosis in the lungs. PMID- 26538869 TI - Indian Academy of Dental Specialists releases it's annual dental science literature as print dental suppliment in association with jpbsonline.org from India, August 2015. PMID- 26538868 TI - Oral antibiotics in trans-rectal prostate biopsy and its efficacy to reduce infectious complications: Systematic review. AB - For the diagnosis of prostate cancer trans-rectal prostate biopsy (TRPB) is used commonly, the procedure is associated with infective complications. There is evidence that antibiotics (ABx) decrease infective events after TRPB, but different regimens are used. To systematically review different regimens of prophylactic oral ABx in TRPB. MEDLINE, EMBASE, clinical trials site, and Cochrane library were searched, experts were consulted for relevant studies. Randomized clinical trials conducted in the last 20 years, which investigated the different oral antibiotic regimens in TRPB, and compared their efficacy to reduce infectious complications were analyzed. Primary outcomes were bacteriuria, urinary tract infection (UTI), fever, bacteremia, and sepsis. Secondary outcomes were the hospitalization rate and the prevalence of ABx-resistant bacteria. Nine trials were eligible with 3012 patients. ABx prevented bacteriuria (3.5% vs. 9.88%), UTI (4.46% vs. 9.75%), and hospitalization (0.21% vs. 2.13%) significantly in comparison with placebo or no treatment. No significant difference was found in all the outcomes of the review between the single dose regimen and the 3 days. The single dose regimen was as effective as the multiple doses except in bacteriuria (6.75% vs. 3.25%), and the prevalence of ABx resistant bacteria (1.57% vs. 0.27%). Quinolones reduced only UTI significantly in comparison with other ABx (chloramphenicol, trimethoprim-sulfamethoxazol). It is essential to prescribe prophylactic ABx in TRPB. No conclusive evidence could be claimed about the superiority of the multiple or the 3 days regimens to the single dose regimen. Unexpectedly, ABx-resistant bacteria were identified more often in the single dose cohorts. PMID- 26538870 TI - Caries management by risk assessment: A review on current strategies for caries prevention and management. AB - The current trend in treating dental caries is using nondestructive risk-based caries management strategies rather than focusing on the restorative treatment alone. Currently, there have been many changes in understanding of the multifaceted nature of caries process and its management. Caries Management by Risk Assessment (CAMBRA) which is an evidence-based approach focuses on determining many factors causing the expression of disease and take corrective action. The clinicians can ascertain what behaviors are increasing a patient's risk for disease and disease progression by evaluating the current caries risk of a patient. With this modern CAMBRA protocol, a novel treatment plan can be designed to arrest dental caries thereby decreasing the chance of cavitation. After the recognition of the multi factorial nature of caries involving the biofilm, the contemporary approaches focused mainly on the various options to cope with the locally out-of-balance oral biofilm and stop the progression of the disease. The initial caries lesions can be diagnosed with modern diagnostic aids and with the help of CAMBRA, reestablishment of the integrity of the tooth surface early on in the caries process will bring great rewards for patients. This review focuses on the repair of hard tooth tissues using noninvasive strategies. PMID- 26538872 TI - Enzymatic antioxidants and its role in oral diseases. AB - Antioxidants are substances that when present at very low concentration inhibits the oxidation of a molecule. It has the capacity to nullify the ill effects of oxidation caused by free radicals in the living organisms. The unpaired electrons of these free radicals are highly reactive and neutralize the harmful reactions of human metabolism. Protection of the body against free radicals is provided by some enzymes which come under a distinctive group, concerned solely with the detoxification of these radicals. Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase are the key enzymatic antioxidants of this defense system by which the free radicals that are produced during metabolic reactions are removed. This review highlights the mechanism of action of enzymatic antioxidants SOD, GPX and catalase and its role in oral disease. PMID- 26538871 TI - Biomarkers in orthodontic tooth movement. AB - Tooth movement by orthodontic treatment is characterized by remodeling changes in the periodontal ligament, alveolar bone, and gingiva. A reflection of these phenomenons can be found in the gingival crevicular fluid (GCF) of moving teeth, with significant elevations in the concentrations of its components like, cytokines, neurotransmitters, growth Factors, and a arachidonic acid metabolites. GCF arises at the gingival margin and can be described as a transudate or an exudate. Several studies have focused on the composition of GCF and the changes that occur during orthodontic tooth movement (OTM). GCF component analysis is a non-invasive method for studying the cellular response of the underlying periodontium. Clinically, GCF can be easily collected using platinum loops, filter paper strips, gingival washings, and micropipettes. A number of GCF biomarkers involve in bone remodeling during OTM. The data suggest that knowledge of all the biomarkers present in the GCF that can be used to mark the changes in tooth that is undergoing orthodontic treatment may be of clinical usefulness leading to proper choice of mechanical stress to improve and to shorten treatment time and avoid side effects. PMID- 26538873 TI - Friction in orthodontics. AB - Conventional wisdom suggests that resistance to sliding (RS) generated at the wire-bracket interface has a bearing on the force transmitted to the teeth. The relative importance of static and kinetic friction and also the effect of friction on anchorage has been a topic of debate. Lot of research work has been done to evaluate the various factors that affect friction and thus purportedly retards the rate of tooth movement. However, relevancy of these studies is questionable as the methodology used hardly simulates the oral conditions. Lately studies have concluded that more emphasis should be laid on binding and notching of archwires as these are considered to be the primary factors involved in retarding the tooth movement. This article reviews the various components involved in RS and the factors affecting friction. Further, research work should be carried out to provide cost effective alternatives aimed at reducing friction. PMID- 26538874 TI - Halitosis - An overview: Part-I - Classification, etiology, and pathophysiology of halitosis. AB - Halitosis is a condition where the breath is altered in an unpleasant manner for the affected individuals and impairs them socially as well as psychologically. Halitosis can be clinically classified as real halitosis, pseudohalitosis, and halitophobia. Real halitosis has oral and extra-oral etiologies and the pathophysiology involves interaction of anaerobic microbes (mainly) with the proteins present in the oral cavity fluids and contents, resulting in production of volatile sulfur compounds (VSCs). These VSCs, beyond responsible for halitosis, can also initiate and accelerate periodontal disease progression. Thus, this review is about the pathophysiology and various etiologies of halitosis, the knowledge of which can help in the betterment of treatment options. PMID- 26538875 TI - Role of proteomics in physiologic and pathologic conditions of dentistry: Overview. AB - Proteomics is the study of structure and function of proteins in a large scale. For any living organism, preteins are considered to be the vital part because of its role in metabolic pathways of cells. These proteins not only play a role in physiological condition of the cell but also in altered manner during pathologic conditions. These altered proteins in diseased conditions are called as biomarkers. Several such biomarkers were identified in oral diseaes. This review is a brief note on proteins involved in odontogenesis and list of altered proteins proteins identified in various dental and oral diseases. The knowledge about the role of proteomics in dentistry and the importance of proteomic studies in early diagnosis and prognostic part of oral diseases helps in appliction of precised and sucessful treatment. PMID- 26538876 TI - Denture bar-coding: An innovative technique in forensic dentistry. AB - Denture markers play an important role in forensic odontology and also in identifying a person. A number of methods are there for identifying dentures from a less expensive technique to a more expensive technique. Out of different denture markers, the bar-coding system is a way of collecting data from the mobile. Even a huge amount of data can be stored in that. It can be easily incorporated during acrylization of the denture and thus could be helpful in identification. This article reviews the strengths of bar-coding and how easily it can be used in the routine procedure. PMID- 26538877 TI - Liaison between micro-organisms and oral cancer. AB - Oral cancer which is a subtype of head and neck, cancer is any neoplastic tissue growth in the oral cavity. It comprises an abnormal mass of cells that foists genetic mutation and impedes the normal cell cycle, resulting in its unrestrained growth. Various studies on the plausible link between oral microbial flora and cancer notwithstanding, our understanding of their link remains obscure and inadequate. The multitude of mechanisms by which the microflora initiate or spur Carcinogenesis are still under study and scrutiny. As is widely known, the oral cavity is an abode to a wide assortment of microbes, each present in contrasting amounts. It is observed that increased growth of the microflora is concomitant with known clinical risk factors for oral cancer. Manifold bacterial species have been found to interfere directly with eukaryotic cellular signaling, adopting a style typical of tumor promoters. Bacteria are also known to impede apoptosis thereby potentially promoting carcinogenesis. The viral role in carcinogenesis (by annulling of p53 tumor suppressor gene and other cellular proteins with subsequent alteration in host genome function) is well documented. Furthermore, the changes occurring in the commensal microflora in accompaniment with cancer development could possibly be used as a diagnostic indicator for early cancer detection. The intention of this review is to obtain a better understanding of the "role" that micro-organisms play in oral cancer etiology. PMID- 26538879 TI - Eagle's syndrome - Masquerading as ear pain: Review of literature. AB - The name styloid process (SP) was derived from the Greek word "stylos" meaning a pillar. It is a bony, cylindrical, needle-shaped projection, which originates from the posterior-inferior side of the petrous bone, immediately in front of the stylomastoid foramen, and goes obliquely down and forward. When elongated leads to pain and discomfort called Eagle's syndrome. Elongated SP accounts approximately to 4-7% of the population, 4% only are symptomatic. PMID- 26538878 TI - Stem cells: An insight into the therapeutic aspects from medical and dental perspectives. AB - The recent advancements in the field of stem cell (SC) biology have increased the hope of achieving the definitive treatments for the diseases which are now considered incurable such as diabetes, Parkinson's disease and other chronic long standing conditions. To achieve this possibility, it is necessary to understand the basic concepts of SC biology to utilize in various advanced techniques of regenerative medicine including tissue engineering and gene therapy. This article highlights the types of SCs available and their therapeutic capacity in regenerative medical and dental fields. PMID- 26538880 TI - Autofluorescence based diagnostic techniques for oral cancer. AB - Oral cancer is one of the most common cancers worldwide. Despite of various advancements in the treatment modalities, oral cancer mortalities are more, particularly in developing countries like India. This is mainly due to the delay in diagnosis of oral cancer. Delay in diagnosis greatly reduces prognosis of the treatment and also cause increased morbidity and mortality rates. Early diagnosis plays a key role in effective management of oral cancer. A rapid diagnostic technique can greatly aid in the early diagnosis of oral cancer. Now a day's many adjunctive oral cancer screening techniques are available for the early diagnosis of cancer. Among these, autofluorescence based diagnostic techniques are rapidly emerging as a powerful tool. These techniques are broadly discussed in this review. PMID- 26538881 TI - Squamous cell carcinoma and dental implants: A systematic review of case reports. AB - Cancer is one of the leading causes of death world-wide. Apart from the most common etiopathological factors related to cancer, at times very rare causes such as irritant or foreign body induced carcinogenesis is not to be overlooked. To systematically review case reports concerned with the association between dental implants and oral squamous cell carcinoma. A Medline (PubMed), Cochrane database, and Google Scholar search was conducted of dental article published in English related to case reports concerned with oral squamous cell carcinoma occurring around dental implants from 2000 to 2014. Twenty articles were retrieved, which included 20 rare case reports which were systematically reviewed and the results were obtained pertaining to age, clinical symptoms, habits, previous history of cancer, potentially malignant disorders, systemic illness, and local factors. It is imperative to identify promptly persisting inflammation associated with implants. Since malignancy may disguise as periimplantitis, especially in patients who are at risk with contributing prominent predisposing factors. PMID- 26538882 TI - Robotics and medicine: A scientific rainbow in hospital. AB - The journey of robotics is a real wonder and astonishingly can be considered as a scientific rainbow showering surprising priceless power in the era of future technologies. The astonishing seven technologies discussed in this paper are da Vinci Robotic surgical system and sperm sorters for infertility, Veebot for blood investigation, Hanako the robotic dental patient for simulating the dental patient and helping a trainee dentist, RP-7 robot who is around-the-clock physician connecting the physician and patient, Robot for Interactive Body Assistance (RIBA) who is a RIBA serving as a nurse, Bushbot serving as a brilliant surgeon, and Virtibot helping in virtual autopsy. Thus, robotics in medicine is a budding field contributing a great lot to human life from before birth to afterlife in seven forms thus gracefully portraying a scientific rainbow in hospital environment. PMID- 26538883 TI - Harvesting dental stem cells - Overview. AB - Dental stem cells have recently become one of the widely researched areas in dentistry. Ever since the identification of stem cells from various dental tissues like deciduous teeth, dental papilla, periodontal ligament and third molars, storing them for future use for various clinical applications was being explored. Dental stem cells were harvested and isolated using various techniques by different investigators and laboratories. This article explains the technical aspects of preparing the patient, atraumatic and aseptic removal of the tooth and its safe transportation and preservation for future expansion. PMID- 26538884 TI - The extended tentacles of laser - From diagnosis to treatment in orthodontics: An overview. AB - Since the introduction of lasers in dentistry in the mid-1990's, research in laser supported dental therapies is progressing at a rapid pace. Orthodontics is no exception. In orthodontics, lasers have many diagnostic, therapeutic, and biomodulating applications. To update the various applications of lasers in orthodontics. Lasers work by delivering energy in the form of light. Laser, striking the biological tissues can either get reflected, absorbed or scattered depending on several factors. Depending on the fate of the emitted laser, it can be applied for different diagnostic, therapeutic and surgical procedures. The knowledge and understanding of different types of lasers and its specific applications is a prerequisite before it can be applied beneficially. In Orthodontics, the versatility of laser has expanded into bonding, curing, debonding, imaging, growth modification, pain reduction, etc. Definitely laser has extended its tentacles from diagnosis to treatment in orthodontics. PMID- 26538885 TI - Posturedontics: How does dentistry fit you? AB - Dentists are at high risk for musculoskeletal disorders (MSD's) due to their work. MSD's is an umbrella term for number of injuries affecting different parts of the body, including joints, muscles, tendons, nerves that can arise from sudden exertion or making the same motions repeatedly. These injuries can develop over time and can lead to long-term disability. Dental professional often develop musculoskeletal problems due to bad working habits, uncomfortable physical posture causing unnecessary musculoskeletal loading, discomfort and fatigue. Ergonomic principles when it is applied, it will help to reduce stress and eliminate many potential injuries and disorders associated with the overuse of muscles, bad posture, and repeated tasks. This can be accomplished by using a proper dental chair, lighting and the selection of ergonomically-friendly equipment to fit the dental professionals physical capabilities and limitations. This review addresses about the basics of ergonomics, positioning, viewing, handling, and prevention of MSD's. PMID- 26538886 TI - Sex determination in forensic odontology: A review. AB - Forensic odontology is the application of dental principles to legal issues. Sex determination is a subdivision of forensic odontology and it is very important especially when information relating to the deceased is unavailable. Sex determination becomes the first priority in the process of identification of a person by a forensic investigator in the case of mishaps, chemical and nuclear bomb explosions, natural disasters crime investigations, and ethnic studies. This article reviews upon the various methods used in sex determination. PMID- 26538887 TI - Oral pigmentation: A review. AB - Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID- 26538888 TI - Role of micronucleus in oral exfoliative cytology. AB - In the last few years, the interest for oral cytology as a diagnostic and prognostic methodology, for monitoring patients in oral potentially malignant disorders and oral cancer has re-emerged substantially. In 1983, buccal mucosal micronuclei assay was first proposed to evaluate genetic instability. There are biomarkers that predict if a potentially malignant disorder is likely to develop into an aggressive tumor. These genotoxic and carcinogenic chemicals have been reported to be potent clastogenic and mutagenic agents which are thought to be responsible for the induction of chromatid/chromosomal aberrations resulting in the production of micronuclei. Various studies have concluded that the gradual increase in micronucleus (MN) counts from normal oral mucosa to potentially malignant disorders to oral carcinoma suggested a link of this biomarker with neoplastic progression. MN scoring can be used as a biomarker to identify different preneoplastic conditions much earlier than the manifestations of clinical features and might specifically be exploited in the screening of high risk population for a specific cancer. Hence, it can be used as a screening prognostic and educational tool in community centers of oral cancer. PMID- 26538889 TI - Tools for evaluating oral health and quality of life. AB - The seven dimensions of quality of life are required for a healthy living. Any impairment or disability affects any one or more of these dimensions resulting in functional impairment or handicap, which indicates the presence of disease. The success of any oral treatment depends on how far the individual is relieved of his disease process. Relief of symptoms provides patient comfort and enable functional activities. This well-being is considered as a measure of oral health and reflects patient satisfaction. This article presents various instruments or tools available in the form of a questionnaire that estimates patient satisfaction and thereby oral health. PMID- 26538890 TI - Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited. AB - Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence. PMID- 26538891 TI - Natural head position: An overview. AB - Cephalometrics has given us a different perspective of interpreting various skeletal problems in the dentofacial complex. Natural head position (NHP) is a reproducible, physiologically determined aspect of function. To determine NHP, a horizontal or vertical reference line outside the crania was used, but preference was given generally to the horizontal. Various intra and extracranial cephalometric horizontal reference planes have been used to formulate diagnosis and plan individualized treatment for an integrated correction of the malocclusion cephalometrics is constantly undergoing refinements in its techniques and analyses to improve the clinical applications. Even though various methods for establishing NHP have been proposed, still it remains a challenge to the clinicians to implement the concept of NHP thoroughly in all the stages of treatment because of practical difficulties in the clinical scenario. PMID- 26538892 TI - A review of clinical and radiological features of cleidocranial dysplasia with a report of two cases and a dental treatment protocol. AB - Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition with generalized dysplasia of bone characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We report two cases presenting with classical features of CCD because of its rarity. PMID- 26538893 TI - Three-dimensional assessment of facial asymmetry: A systematic review. AB - For patients with facial asymmetry, complete and precise diagnosis, and surgical treatments to correct the underlying cause of the asymmetry are significant. Conventional diagnostic radiographs (submento-vertex projections, posteroanterior radiography) have limitations in asymmetry diagnosis due to two-dimensional assessments of three-dimensional (3D) images. The advent of 3D images has greatly reduced the magnification and projection errors that are common in conventional radiographs making it as a precise diagnostic aid for assessment of facial asymmetry. Thus, this article attempts to review the newly introduced 3D tools in the diagnosis of more complex facial asymmetries. PMID- 26538894 TI - India's baby boomers: In driving need for dental care. AB - The present paper aims to review the literature on increasing health care challenges and needs of a growing Indian geriatric population. It also focuses on the need to overcome the shortfalls in its current oral health status in elderly. This review is based on a PubMed database search engine published in the period from 1990 to 2010 in various dental journals. Different strategies are designed to provide better facilities and easy access of these facilities not only to elderly living in the city but to the one's in rural areas. It is emphasized that geriatric dentistry should be included in the educational systems to help resolve problems of oral health care for the elderly in India. PMID- 26538895 TI - Construction of a three-dimensional finite element model of maxillary first molar and it's supporting structures. AB - The finite element method (FEM) is a powerful computational tool for solving stress-strain problems; its ability to handle material inhomogeneity and complex shapes makes the FEM, the most suitable method for the analysis of internal stress levels in the tooth, periodontium, and alveolar bone. This article intends to explain the steps involved in the generation of a three-dimensional finite element model of tooth, periodontal ligament (PDL) and alveolar bone, as the procedure of modeling is most important because the result is based on the nature of the modeling systems. Finite element analysis offers a means of determining strain-stress levels in the tooth, ligament, and bone structures for a broad range of orthodontic loading scenarios without producing tissue damage. PMID- 26538896 TI - A case-control study to detect the extent of DNA damage in oral lichen planus and oral lichenoid reactions using comet assay. AB - AIM: This study aims to quantify the extent of DNA damage in lymphocytes of patients with oral lichen planus (OLP) and oral lichenoid reactions (OLRs) using comet assay. METHODOLOGY: Lymphocytes from peripheral blood were subjected to alkaline comet assay. Comet length (CL), head diameter (HD), percentage of DNA in head, tail length (TL), percentage of DNA in tail, tail intensity, tail mean and tail moment were compared between study group (OLP and OLR) and control group using Student's t-test. Pearson's correlation coefficient was used to examine the linear association between the variables. RESULTS: Significantly higher levels of DNA damage was present in study group as reflected by CL, HD and TL, tail intensity and tail moment with P = 0.0001; percentage of DNA in head and tail with P = 0.02 and tail mean with P = 0.012. CONCLUSION: This study brings out the fact that DNA damage measured by comet assay was greater in the study group when compared to the control group. As a reflection of uniqueness, this study crowns the scenario with respect to early detection and prevention of potentially malignant disorders and the process of malignant transformation. PMID- 26538897 TI - Estimation and comparison of serum cortisol levels in periodontally diseased patients and periodontally healthy individuals: A clinical-biochemical study. AB - INTRODUCTION: Psychological conditions, particularly psychosocial stress have been implicated as risk indicators of periodontal disease. Stress increases cortisol production from the adrenal cortex by stimulating an increase in the release of ACTH from the pituitary gland. Increased cortisol production suppresses the immune response and increases the potential of periodontal tissue destruction. AIM: The aim of the present study was to estimate and compare the serum cortisol levels in periodontally diseased patients and periodontally healthy individuals. MATERIALS AND METHODS: Total of 45 subjects were recruited for this study and were categorized into three groups. Group I - Comprised of aggressive periodontitis patients (n = 15), Group II - Chronic periodontitis patients (n = 15), and Group III - Healthy controls (n = 15). Serum samples were collected from each of the groups and cortisol levels were determined using cortisol immunoassay kit. Clinical examination covered probing depth, gingival index (GI), gingival recession, plaque index, and clinical attachment level. The statistical analysis was done using nonparameteric t-test and Spearman's rank correlation coefficient. RESULTS: With respect to cortisol, the levels were higher in Group-I compared to the other groups. On comparison of mean cortisol levels among the groups, the values were statistically significant between Group I and Group-III. Group-I showed a significant negative correlation between cortisol levels and GI. CONCLUSION: Within the limits of the study serum cortisol levels was higher in the chronic periodontitis group compared to the other groups. Positive correlation was found between the cortisol levels and other clinical parameters except for the GI. PMID- 26538898 TI - Comparison of flexural strength in three types of denture base resins: An in vitro study. AB - AIM: The aim of this study was to evaluate whether the flexural strength of a commercially available, heat polymerized acrylic denture base material could be improved using reinforcements. MATERIALS AND METHODS: A total of 30 specimens (65 mm * 10 mm * 3 mm) were fabricated; the specimens were divided into three groups with 10 specimens each. They were Group 1 - conventional denture base resins, Group 2 - high impact denture base resins, and Group 3 - glass reinforced denture base resins. The specimens were loaded until failure on a three-point bending test machine. An one-way analysis of variance was used to determine statistical differences among the flexural strength of three groups. Data were analyzed by SPSS software version 21.0(c) (IBM Corporation, Armonk, NY, USA) and the results were obtained. RESULTS: The flexural strength values showed statistically significant differences among experimental groups (P < 0.005). CONCLUSION: Within the limitations of the study polymethyl methacrylate (PMMA) reinforced with glass fibers showed the highest flexural strength values this was followed by PMMA reinforced with butadiene styrene, and the least strength was observed in the conventional denture base resins. PMID- 26538899 TI - Digital model as an alternative to plaster model in assessment of space analysis. AB - INTRODUCTION: Digital three-dimensional models are widely used for orthodontic diagnosis. The purpose of this study was to appraise the accuracy of digital models obtained from computer-aided design/computer-aided manufacturing (CAD/CAM) and cone-beam computed tomography (CBCT) for tooth-width measurements and the Bolton analysis. MATERIALS AND METHODS: Digital models (CAD/CAM, CBCT) and plaster model were made for each of 50 subjects. Tooth-width measurements on the digital models (CAD/CAM, CBCT) were compared with those on the corresponding plaster models. The anterior and overall Bolton ratios were calculated for each participant and for each method. The paired t-test was applied to determine the validity. RESULTS: Tooth-width measurements, anterior, and overall Bolton ratio of digital models of CAD/CAM and CBCT did not differ significantly from those on the plaster models. CONCLUSION: Hence, both CBCT and CAD/CAM are trustable and promising technique that can replace plaster models due to its overwhelming advantages. PMID- 26538900 TI - Comparative analysis of gingival crevicular fluid a disintegrin and metalloproteinase 8 levels in health and periodontal disease: A clinic biochemical study. AB - AIM AND BACKGROUND: A disintegrin and metalloproteinase 8 (ADAM8) is a marker belonging to the class of ADAM family of metalloproteinase which is found to be involved in inflammation and bone resorption in periodontal disease by acting as osteoclast stimulating factor. In several systemic inflammatory diseases, elevated levels of ADAM8 are detected in human serum and other body fluids. Recently, ADAM8 was even detected in gingival crevicular fluid (GCF) of patients with periodontal diseases. Hence, the aim of the study was to estimate the levels of ADAM8 in GCF of healthy and chronic periodontitis subjects. MATERIALS AND METHODS: Periodontal examination and collection of GCF by the extracrevicular method was performed in 30 subjects selected randomly and categorized into two groups. Group I (healthy, n = 15) and Group II (chronic periodontitis, n = 15). ADAM8 levels in GCF were estimated by enzyme-linked immunosorbent assay. RESULTS: ADAM8 was detected in both Group I and II. Highest mean ADAM8 concentration was obtained for Group II, whereas the lowest concentration was seen in Group I. This suggests that ADAM8 levels increase proportionally with the progression of periodontal disease. There was a significant correlation between ADAM8 levels and clinical parameters in the study group. CONCLUSION: The results of our study indicate that the ADAM8 levels in GCF are positively associated with periodontal disease, which may provide a useful tool in monitoring its progression. Nevertheless, further longitudinal studies are required with larger sample sizes in which ADAM8 levels are progressively estimated and compared to baseline values. PMID- 26538901 TI - Erosive potential of commonly used beverages, medicated syrup, and their effects on dental enamel with and without restoration: An in vitro study. AB - AIM: This study evaluates erosive potential of commonly used beverages, medicated syrup, and their effects on dental enamel with and without restoration in vitro. MATERIALS AND METHODS: Test medias used in this study included carbonated beverage, noncarbonated beverage, high-energy sports drink medicated cough syrup, distilled water as the control. A total of 110 previously extracted human premolar teeth were selected for the study. Teeth were randomly divided into two groups. Test specimens were randomly distributed to five beverages groups and comprised 12 specimens per group. Surface roughness (profilometer) readings were performed at baseline and again, following immersion for 14 days (24 h/day). Microleakage was evaluated. The results obtained were analyzed for statistical significance using SPSS-PC package using the multiple factor ANOVA at a significance level of P < 0.05. Paired t-test, Friedman test ranks, and Wilcoxon signed ranks test. RESULTS: For surface roughness high-energy sports drink and noncarbonated beverage showed the highly significant difference with P values of 0.000 and 0.000, respectively compared to other test media. For microleakage high energy sports drink had significant difference in comparison to noncarbonated beverage (P = 0.002), medicated syrup (P = 0.000), and distilled water (P = 0.000). CONCLUSION: High-energy sports drink showed highest surface roughness value and microleakage score among all test media and thus greater erosive potential to enamel while medicated syrup showed least surface roughness value and microleakage among all test media. PMID- 26538902 TI - Evaluation of Health on the Net seal label and DISCERN as content quality indicators for patients seeking information about thumb sucking habit. AB - AIMS: The aim of this study was to evaluate the reliability of websites on the thumb sucking habit using DISCERN instrument and Health on the Net (HON) seal code at a single moment in time. SUBJECTS AND METHODS: An Internet search engine (www.google.com) was used to identify websites comprising information on "thumb sucking habit." Of over 204,000 links for thumb sucking habit, the first 100 were analyzed in detail. After excluding discussion groups, news and video feeds, and removing carbon copy sites, only 36 relevant websites remained, which were then assessed using the DISCERN instrument and HON seal code. Using the 16 questions of DISCERN for assessing the reliability and quality of the consumer information which were scored from 1 to 5, an appropriate index of the quality of the information was generated. All the assessed websites were also checked for presence or absence of HON seal code. RESULTS: The maximum score attainable for an outstanding website is 80. Of the 36 websites that were scored the highest score obtained by one of the websites according to the DISCERN tool was 55 of 80, and the lowest score achieved was 16 of 80. The websites achieving the maximum and minimum score were children.webmd.com and thebehaviorsolution.com, respectively. The HON seal was displayed only in three websites, which were medicinenet.com, righthealth.com, and children.webmd.com. CONCLUSIONS: By directing patients to validated websites on the thumb sucking habit, clinicians can ensure patients find appropriate information. PMID- 26538903 TI - Gender identification and morphologic classification of tooth, arch and palatal forms in Saudi population. AB - AIMS: To determine various tooth form, arch form, and palatal form with gender identification between males and females of the Saudi population. MATERIALS AND METHODS: Irreversible hydrocolloid impressions were made of the maxillary teeth of 100 dentate male and female subjects to obtain study casts. A standardized procedure was adopted to photograph the maxillary dental arches and the maxillary central incisors on the study casts taken from each subject. The outline form of tooth, arch, and palatal form were determined using a standardized method. The average of six prosthodontist's evaluation was considered who classified the outline tracings visually. The statistical analysis was performed using Chi Square and results tabulated. RESULTS: The predominant tooth is combination form in males and ovoid form in females, the predominant arch is ovoid form in males and square form in females and the predominant palatal form are both U and V shaped in males and U-shaped in females. CONCLUSION: Except for the tooth form there was a significant difference with arch and palatal form among males and females of the population group studied. The determined tooth, arch and palatal forms are useful in selection and arrangement of artificial teeth among Saudi edentulous population group. Generalizing from the study is questionable as the sample size is small. Further studies should be conducted in a larger sample to confirm the study results. PMID- 26538904 TI - Prevalence of oral squamous cell carcinoma of tongue in and around Davangere, Karnataka, India: A retrospective study over 13 years. AB - AIM: The aim was to determine the frequency and distribution of oral squamous cell carcinoma (OSCC) involving tongue among patients by studying biopsy specimens obtained from the archives of the Department of Oral and Maxillofacial Pathology, College of Dental Sciences, Davangere, Karnataka, India, during the past 13 years. METHODOLOGY: Data for the study were retrieved from the case records of patients. Analyzed clinical variables included age, sex, anatomical site, and histological diagnosis. RESULTS: Of the 369 squamous cell carcinoma involving head and neck region, we found 52 biopsies reported exclusively involving tongue. Lateral border of the tongue was most commonly involved (43 cases, 82.7%), followed by base of tongue and posterior part of tongue. The patient were affected over a wide range of 27-80 years with mean age of 55.75 years and peak incidence was seen in the fourth and fifth decades of life, with the male: female ratio of 1.7:1. CONCLUSION: The prevalence rate of OSCC involving tongue showed a definite geographic variation when compared with a study done in other parts of the world. PMID- 26538905 TI - A clinical study on oral lichen planus with special emphasis on hyperpigmentation. AB - BACKGROUND: Oral lichen planus (OLP) is a unique disorder affecting generally the older age group. Numerous studies have been done on various aspects of OLP such as pathogenesis, rate of malignant transformation, etc. However, very few studies are available with respect to clinical features especially association of hyperpigmentation and OLP. This study aims at studying the clinical aspects of OLP and study the association between hyperpigmentation and OLP in a south Indian population. MATERIALS AND METHODS: A total of 58 patients with OLP who attended the outpatient department of our institution were included in the study and a complete history, followed by thorough intraoral examination was done. All the data were recorded and assessed for statistical analysis using SPSS software. RESULTS: We found that the male to female ratio affected with OLP was 1:1 and the most common form of OLP that was seen was the reticular subtype. Also, buccal mucosa was the most common affected site and more than 60% patients had hyperpigmentation associated with the site affected by OLP. We found a statistically significant relation between the reticular type of OLP and the older age group (51-70 years) with hyperpigmentation. CONCLUSION: Although further studies are required to say anything conclusively, post-inflammatory changes occurring the mucosa due to OLP could be a cause for hyperpigmentation in the sites affected. PMID- 26538906 TI - Clinical evaluation of nonsyndromic dental anomalies in Dravidian population: A cluster sample analysis. AB - AIM: To record the prevalence rate of dental anomalies in Dravidian population and analyze the percentage of individual anomalies in the population. METHODOLOGY: A cluster sample analysis was done, where 244 subjects studying in a dental institution were all included and analyzed for occurrence of dental anomalies by clinical examination, excluding third molars from analysis. RESULTS: 31.55% of the study subjects had dental anomalies and shape anomalies were more prevalent (22.1%), followed by size (8.6%), number (3.2%) and position anomalies (0.4%). Retained deciduous was seen in 1.63%. Among the individual anomalies, Talon's cusp (TC) was seen predominantly (14.34%), followed by microdontia (6.6%) and supernumerary cusps (5.73%). CONCLUSION: Prevalence rate of dental anomalies in the Dravidian population is 31.55% in the present study, exclusive of third molars. Shape anomalies are more common, and TC is the most commonly noted anomaly. Varying prevalence rate is reported in different geographical regions of the world. PMID- 26538907 TI - Prediction of age and gender using digital radiographic method: A retrospective study. AB - AIM AND OBJECTIVE: To investigate age, sex based on gonial angle, width and breadth of the ramus of the mandible by digital orthopantomograph. MATERIALS AND METHODS: A total of 200 panoramic radiographic images were selected. The age of the individuals ranged between 4 and 75 years of both the gender - males (113) and females (87) and selected radiographic images were measured using KLONK image measurement software tool with linear, angular measurement. The investigated radiographs were collected from the records of SRM Dental College, Department of Oral Medicine and Radiology. Radiographs with any pathology, facial deformities, if no observation of mental foramen, congenital deformities, magnification, and distortion were excluded. RESULTS: Mean, median, standard deviation, derived to check the first and third quartile, linear regression is used to check age and gender correlation with angle of mandible, height and width of the ramus of mandible. CONCLUSION: The radiographic method is a simpler and cost-effective method of age identification compared with histological and biochemical methods. Mandible is strongest facial bone after the skull, pelvic bone. It is validatory to predict age and gender by many previous studies. Radiographic and tomographic images have become an essential aid for human identification in forensic dentistry forensic dentists can choose the most appropriate one since the validity of age and gender estimation crucially depends on the method used and its proper application. PMID- 26538908 TI - Coalition of attitude and practice behaviors among dental practitioners regarding pregnant patient's oral health and pregnant patient's perception toward oral health in and around Pondicherry. AB - BACKGROUND: This study aims to evaluate the knowledge, attitude, practice behaviors among general dental practitioners and assess the perception toward oral health by pregnant patients in and around Puducherry. METHODOLOGY: A self designed and structured questionnaire was used to obtain information from the dental practitioner and the pregnant patients. RESULTS: The majority of the dental practitioners had a lack of knowledge, attitude, practice behaviors regarding pregnant patient's oral health and similarly majority of pregnant patient's perception toward oral health was poor. CONCLUSIONS: Drowning and dilemmatic attitude and practice behavior of dentists to be streamlined to render right care to the pregnant women at the right time. Perplexing perception toward oral health care by pregnant women to be overcome to orient them to understand the impact of oral health on their general systemic health. PMID- 26538909 TI - An in vitro evaluation of the demineralization inhibitory effect of F(-) varnish and casein phosphopeptide-amorphous calcium phosphate on enamel in young permanent teeth. AB - AIMS AND OBJECTIVES: To determine the demineralization inhibitory potential of fluoride varnish and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and to compare and evaluate the additive effect of fluoride varnish + CPP-ACP. MATERIALS AND METHODS: Ten healthy premolar teeth that were extracted for orthodontic purposes were collected, and each tooth was longitudinally sectioned buccolingually and mesiodistally into four sections. The teeth were then assigned to four different treatment groups namely fluoride varnish, CPP-ACP, F(-) varnish followed by CPP-ACP and control. The prepared enamel samples were suspended in an artificial caries challenge for 10 days. The demineralizing inhibitory effects of the groups were recorded using polarized light microscopy. STATISTICAL ANALYSIS USED: Statistical analysis was carried out using analysis of variance and Duncan's multiple range tests. RESULTS: The mean lesion depths of all the groups were Group 1 (fluoride varnish): 104.71, Group 2 (CPP-ACP): 127.09, Group 3: (F( ) varnish + CPP-ACP): 82.34, Group 4 (control): 146.93. CONCLUSION: Demineralization inhibitory potential on the additive use of F(-) varnish and casein phosphopeptide was superior to fluoride varnish or CPP-ACP applied alone on the enamel of young permanent teeth. PMID- 26538910 TI - Evaluation of sealing ability two self-etching adhesive systems and a glass ionomer lining LC under composite restoration in primary tooth: An in vitro study. AB - AIMS AND OBJECTIVES: To evaluate the sealing ability of two self-etching adhesive systems and glass ionomer cement (GIC) lining Light cure (LC) under composite restorations in primary teeth. MATERIALS AND METHODS: Class V cavities are prepared on the cervical third of the facial and lingual surfaces of primary molars. The specimens are then assigned into four experimental groups. The restored primary molars are stored in distilled water and subjected to thermocycling. Each section was examined using a stereomicroscope to assess dye penetration at the margin of the restoration and evaluated via pictures. STATISTICAL ANALYSIS USED: The degree of microleakage was analyzed using Kruskal Wallis test and the intergroup significance by multiple comparison analysis. RESULTS: The mean rank of the groups are Group I (Adper PromptTM + Z-100) 19.44, Group II (UniFil BOND + Solare) 5.38, Group III (GIC lining LC + Z-100) 20.06, and Group IV (GIC lining LC + Solare) 21.13 with the P < 0.001. CONCLUSION: Composite resin restorations bonded with two-step self-etching adhesive system (UniFil Bond) exhibited lesser microleakage than one-step self-etching adhesive system (AdperpromptTM) in primary teeth. PMID- 26538911 TI - Sprue design alterations and its effect on the properties of base metal alloy castings: An in vitro study. AB - INTRODUCTION: To study the effect of various sprue designs on the properties of base metal alloy castings. The base metal alloys are extensively used for their excellent properties such as an increase in hardness, high melting range, high elastic modulus, its compatibility with ceramic material and low cost. However, to improve the properties of the base metal alloys is an ongoing research leading to various modifications in their fabrication procedure - which include sprue designs and their mode of attachment to the wax pattern. AIMS AND OBJECTIVES: Study compared the effect of three sprue designs viz. conical sprue, cylindrical sprue and bottleneck sprue on the properties of mass and microhardness of base metal alloy castings. MATERIALS AND METHODS: A prefabricated wax mesh pattern was selected for the fabrication of the alloy test samples in the study. The cylindrical sprue design was connected to the mesh pattern with a straight attachment. The bottleneck sprue design was connected to the mesh pattern with a constricted attachment. The conical sprue design was connected to the mesh pattern with a flared attachment. In this manner, ten samples for each of the three different sprue designs were prepared. RESULTS: The obtained value for mass and microhardness were subjected to statistical analysis. ANOVA test was performed to determine the difference between the sprue designs. CONCLUSION: The bottleneck sprue, conical sprue, and cylindrical sprue designs did not exert any apparent influence on the mass and microhardness. PMID- 26538912 TI - Root coverage using subepithelial connective tissue graft with platelet-rich plasma in the treatment of gingival recession: A clinical study. AB - INTRODUCTION: The presence of gingival recession associated with an insufficient amount of keratinized tissue may indicate gingival augmentation procedure. It is a multifaceted problem for which several treatment options are available. The most predictable technique used for gingival augmentation is the subepithelial connective tissue graft (SCTG). Platelet-rich plasma (PRP) is an enhanced source of growth factors and helps in accelerated periodontal repair and regeneration. AIMS: The aim of this study was to evaluate the efficacy of SCTG along with PRP in the treatment of Miller's class I and II gingival recessions. MATERIALS AND METHODS: Eleven subjects with Miller's class I and II gingival recessions were treated using SCTG with PRP. Clinical variables, including plaque index, gingival index, recession depth (RD), Recession width (RW), width of the keratinized gingiva, probing pocket depth (PD) and clinical attachment level (CAL) were recorded. Patients were recalled at baseline, 3 months, 6 months and 1-year after surgery and clinical recordings were taken. Root coverage percentage (%) was measured at the end of 1-year. RESULTS: The clinical parameters were analyzed during the follow-up period by repeated measures ANOVA test. Twelve months follow up results showed significant improvements in all the clinical parameters. Reduction of recession resulted in a significant decrease in CAL, PD, RW and RD at the end of 12 months. A statistically significant gain in width of keratinized gingiva and a mean root coverage of 84.72 +/- 19.10 was obtained at the end of 12 months. CONCLUSION: From the results of this study, it may be concluded that SCTG with PRP is an effective and predictable method to treat miller's class I and II gingival recession. PMID- 26538913 TI - Upper and lower pharyngeal airway space in West-Tamil Nadu population. AB - AIM: To compare the upper and lower pharyngeal airway (LPA) width in Class II malocclusion patients with low, average, and high vertical growth patterns. STUDY DESIGN: Cross-sectional analytical study. MATERIALS AND METHODS: Pretreatment lateral cephalometric films of 90 Class II subjects were used to measure the upper and LPAs. The inclusion criteria were subjects of West-Tamil Nadu, aged between 14 and 25 years, only skeletal Class II subjects of either gender and no pharyngeal pathology at initial visit. The sample comprised a total of 90 Class II subjects divided into three groups according to the vertical facial pattern: Normodivergent (n = 30), hypodivergent (n = 30), and hyperdivergent (n = 30). The assessment of upper and LPAs was done according to McNamara's airway analysis. STATISTICAL ANALYSIS: The intergroup comparison of the upper and LPAs was performed with one-way analysis of variance and the Tukey test was used to compare among the various vertical patterns. RESULTS: Skeletal Class II subjects with hyperdivergent facial pattern showed statistically significant narrow upper pharyngeal width when compared to normodivergent and hypodivergent facial patterns. No statistically significant difference was found in the lower pharyngeal width in all three vertical facial growth patterns. CONCLUSION: Subjects with Class II malocclusions and hyperdivergent growth pattern have significantly narrow upper pharyngeal airway space when compared to other two vertical patterns. Narrow pharyngeal airway space is one of the predisposing factors for mouth breathing and obstructive sleep apnea. PMID- 26538914 TI - Association between chronic periodontitis and hypertension in South Indian population: A cross-sectional study. AB - AIM: The aim of this work was investigating if there is any association between chronic periodontitis and hypertension, to assess any individual relationship with Basal metabolic index (BMI) and any association with white blood cell count (WBC count) in South Indian population. SETTINGS AND DESIGN: This study is a cross-sectional study. The study sample consisted of 77 patients between the age group of 30-50 years, who were included after excluding risk factors for hypertension. SUBJECTS AND METHODS: This cross-sectional study was conducted in Sree Balaji Dental College in the Outpatient Department of Periodontology. Blood pressure (BP) was recorded in the sitting, standing, and lying positions. The three positions were examined to assess the mean value of BP. Other data collected include sociodemographic details, diet, education status, height, weight, BMI, and WBC. The periodontal status of the subjects was assessed by the bleeding index (Ainamo and Bay) and community periodontal index by community periodontal index and treatment needs. STATISTICAL DATA: The statistical data were assessed by SPSS software version 17. RESULTS: There were 77 subjects participated in this study. However, there was an association between BMI sitting systolic BP is negative the P = 0.044, which is significant. Mean of generalized chronic periodontitis in sitting systolic BP is 118.0833 (95% confidence intervals 112.17 +/- 123.99). CONCLUSIONS: We did not find any statistical significance between these two variables. However, this study is a cross sectional study further; longitudinal studies need to be done to establish the true phenomena. PMID- 26538915 TI - Comparative evaluation of the effect of denture cleansers on the surface topography of denture base materials: An in-vitro study. AB - AIMS: The aim was to evaluate and compare the effects of three chemically different commercially available denture cleansing agents on the surface topography of two different denture base materials. MATERIALS AND METHODS: Three chemically different denture cleansers (sodium perborate, 1% sodium hypochlorite, 0.2% chlorhexidine gluconate) were used on two denture base materials (acrylic resin and chrome cobalt alloy) and the changes were evaluated at 3 times intervals (56 h, 120 h, 240 h). Changes from baseline for surface roughness were recorded using a surface profilometer and standard error of the mean (SEM) both quantitatively and qualitatively, respectively. Qualitative surface analyses for all groups were done by SEM. STATISTICAL ANALYSIS USED: The values obtained were analyzed statistically using one-way ANOVA and paired t-test. RESULTS: All three denture cleanser solutions showed no statistically significant surface changes on the acrylic resin portions at 56 h, 120 h, and 240 h of immersion. However, on the alloy portion changes were significant at the end of 120 h and 240 h. CONCLUSION: Of the three denture cleansers used in the study, none produced significant changes on the two denture base materials for the short duration of immersion, whereas changes were seen as the immersion periods were increased. PMID- 26538916 TI - Efficacy of curcumin as an adjunct to scaling and root planning in chronic periodontitis patients: A clinical and microbiological study. AB - BACKGROUND AND OBJECTIVES: Curcumin is a naturally occurring anti-inflammatory agent with various biologic and medicinal properties. Its therapeutic applications have been studied in a variety of conditions, but only few studies have evaluated the efficacy of curcumin as local drug delivery agent and in the treatment of periodontitis. The present study was to evaluate the efficacy of the adjunctive use of curcumin with scaling/root planing as compared with scaling/root planing alone in the treatment of the chronic periodontitis. MATERIALS AND METHODS: Thirty patients with two sites in the contralateral quadrants having probing pocket depths (PPDs) of >=5 mm were selected. Full mouth scaling and root planing (SRP) was performed followed by application of curcumin gel on a single side. Assessment of plaque index (PI), gingival index (GI), PPD, and clinical attachment levels (CALs) were done at baseline and at 4(th) week. Microbiologic assessment with polymerase chain reaction was done for Porphyromonas gingivalis, Tanerella forsythia, and Treponema denticola by collection of plaque samples. RESULTS: The results revealed that there was a reduction in PI, GI, probing depth, CAL, and microbiologic parameters in test sites following SRP and curcumin gel application, when compared with SRP alone in control group. CONCLUSION: The local application of curcumin in conjunction with scaling and root planing have showed improvement in periodontal parameters and has a beneficial effect in patients with chronic periodontitis. PMID- 26538917 TI - Clinical evaluation of direct composite restoration done for midline diastema closure - long-term study. AB - PURPOSE OF THE STUDY: The aim of this study was to evaluate clinically the performance of composite resin used to restore midline diastema between the maxillary and mandibular central incisors. METHODOLOGY: Direct composite restorations were done for 45 patients with midline diastema between the maxillary and mandibular central incisors. Standard protocols were followed for the placement of composite resin for the diastema closure, and recall visits were made for every 6 months for a period of 60 months for evaluation of the success of these restorations made. Qualified dental personnel examined the restorations made. RESULTS: Clinical evaluations were done after the restorations had been in place for an average of 6 months. Results indicate that none of the restorations were totally lost, and resulting in a 91% overall retention rate for the period of 60 months. About 62% of the restorations made had no noticeable color difference with that of the adjacent tooth, and gingival health indicated 73% of the sample was without any signs of inflammation. CONCLUSIONS: Composites restored for diastemas exhibit satisfactory survival rates placed with recommended placement protocols and without occlusal loading. PMID- 26538918 TI - The efficiency of 2.5% sodium hypochlorite in preventing inoculation of periapical tissues with contaminated patency files: An ex vivo evaluation. AB - The purpose of this in vitro study was to analyze the effectiveness of 2.5% sodium hypochlorite (NaOCl) in preventing inoculation of periapical tissue with contaminated patency files. Fifty single-rooted teeth with single canals were used in the study. They were randomly divided into five groups of which two were experimental groups, two positive controls, and one negative control group. After root canal preparation, teeth in Group I (experimental) were filled with 2.5 NaOCl and #15 stainless steel K-files contaminated with Streptococcus sanguis (ATCC# 10556) were allowed to pass through the root canal into the culture medium and cultured. Teeth in Group II (experimental) were also filled with NaOCl, but contaminated files used in this group were immersed in 2.5% NaOCl for 10 s prior to being placed in the canal. The negative control used sterile files pass through 2.5% NaOCl into the culture medium. The first positive control used contaminated patency files in teeth with saline. The second positive control group placed contaminated files into broth next to teeth filled with NaOCl (to evaluate potential chlorine leakage). The results were as follows. Both the experimental groups and the negative control group showed no growth. Both the positive control groups 100% growth for S. sanguis. This indicates that the NaOCl present in the canal after irrigation was sufficient to kill the test organism. PMID- 26538919 TI - Evaluation of dental age in protein energy malnutrition children. AB - BACKGROUND: Knowledge of dental age is very essential for a dental practitioner in planning treatment and it is a supplementary source of information for Pediatrician, Orthopedician and Endocrinologist. There are few studies in the literature about the comparison of dental with chronological age in protein energy malnutrition children (PEM). Accordingly, the aim of this study was to evaluate and compare dental age and chronological age in PEM children. AIMS AND OBJECTIVE: To determine and compare dental age and chronological age in PEM children. METHODS: A total of 100 PEM children within the age range of 6-12 years were selected. Chronological age was recorded using date of birth. Dental age was assessed by Demirjian's method using orthopantomogram. Comparison of two ages was done using the unpaired Student's t-test and Pearson's correlation coefficient. RESULTS: Dental age was retarded compared to chronological age, and the difference was statistically significant (P < 0.001). The correlations between two ages were positive in both sexes. CONCLUSION: Dental age was delayed in our sample of 100 PEM children. Dental age can be considered as variable for diagnosing growth retardation in PEM children. Further studies are required to support our findings. PMID- 26538920 TI - Evaluation of caries in deciduous second molar and adjacent permanent molar in mixed dentition. AB - AIM: This study was done to evaluate association of caries in deciduous second molar and adjacent permanent first molar, tooth surface more involved in permanent first molar and to assess the parental awareness regarding the eruption of permanent first molar. SUBJECTS AND METHODS: Three hundred and ten children (160 boys, 150 girls) of mixed dentition aged between 6 and 11 years were included. Presence or absence of paired association of caries in primary second molar and adjacent permanent first molar, of both the jaws, were noted. Parental awareness regarding the child's dentition was asked by pointing the maxillary and mandibular permanent first molar. RESULTS: Pearson Chi-square test was used. Significance was noted in both sexes between paired nonassociation of caries in mandibular primary second molar and mandibular permanent molar (P =0.01) and paired nonassociation of caries in primary maxillary second molar and maxillary permanent first molar in girls only (P =0.04). Parental awareness that permanent first molar has erupted was 24.83% and not to be exfoliated and replaced was 22.9% for both the sexes. In permanent teeth of both the sexes, the occlusal surface was more involved with caries in maxillary teeth; the buccal surface was more involved in mandibular teeth. About 10% of the sample did not have caries in both maxillary and mandibular permanent first molar. CONCLUSIONS: Paired association of caries of primary second molar and permanent first molar though found in large number of cases was not significant. It is clear that parental awareness is less regarding the child's oral health. Thus, community-based awareness program has to be conducted to emphasize on pediatric oral health status and care. PMID- 26538921 TI - Comparative evaluation of effect of different irrigation solutions against Enterococcus faecalis: A polymerase chain reaction-based study. AB - Enterococcus faecalis is the most isolated or detected species from oral infections including marginal periodontitis, infected root canals, periradicular abscesses and also detected in cases of failed endodontic therapy. To prevent endodontic treatment failure irrigation is mandatory for the effective removal of smear layer, pulp tissue, and microorganisms. Cultivation and other traditional identification methods have been demonstrated to have several limitations when it comes to microbiological identification. Polymerase chain reaction was selected because it has an added advantage over traditional microbiological methods. MATERIALS AND METHODS: Twenty single rooted premolars were taken were taken stored in 0.1% thymol solution at 4 degrees C decoronated to obtain 12 mm length, teeth were autoclaved at 121 degrees C, canals were instrumented up to 35k file (International Organization for Standardization). The samples were randomly divided into three groups Group I - 5.25% sodium hypochlorite (NaOCL) and 17% ethylenediaminetetraacetic acid (EDTA), Group - II 5.25% NaOCL and 2% chlorhexidine (CHX), Group III - 5.25% NaOCL and 17% EDTA and 2% CHX. RESULTS: The results showed that Group III which is 5% NaOCl followed by 17% EDTA and followed by 2% CHX showed maximum antimicrobial activity in all the three different time intervals. PMID- 26538922 TI - Correlation of lip prints and lip competence in children. AB - INTRODUCTION: Individual identification is a significant and difficult task in forensic search; it was based on logical values. A lip print is different in every living individual and does not change with time so it can be used as a tool in forensic investigations. The present work aimed to find out the correlation between lip prints and lip competence in the pediatric population of Davangere city. MATERIALS AND METHODS: The study sample comprised of 103 children that is, 49 males and 54 females of aged between 4 and 14 years. The lip impression was made on a strip of cellophane tape on adhesive portion; it was then placed to a white bond paper. This serves as permanent record. In this study, we are followed the classification of patterns of the lines on the lips proposed by Tsuchihashi. For recording lip competence, we considered Ballard criteria. RESULTS: Chi-square test was used to find out the degree of association between variables and to check out whether statistically significant differences exist. CONCLUSION: Lip prints are unique for every person and show differences according to the race and the ethnic origins of a person. The present study confirmed the distinctiveness of cheiloscopy but disproves any statistical correlation of lip print with lip competency. PMID- 26538923 TI - Evaluation of remineralization capacity of casein phosphopeptide-amorphous calcium phosphate on the carbamide peroxide treated enamel. AB - OBJECTIVE: The aim of this study was to evaluate the potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in remineralizing the bleached enamel surface using micro-hardness. MATERIALS AND METHODS: Thirty human enamel slabs were randomly divided into three groups (n = 10). Groups A and B were exposed to 20% carbamide peroxide and 35% carbamide peroxide gel, respectively. After the exposure to the bleaching agent, the slabs were kept in artificial saliva for 1-week. Group C (control group) were kept in artificial saliva for 1-week. Vickers micro-hardness test was performed by Leica VMHT-Mot micro-hardness tester. CPP-ACP (Gc Tooth Mousse, Melbourne, Australia) was then applied to specimens of Groups A and B for 3 min for 2 weeks. Micro-hardness values of postbleach Group A (Ar) and Group B (Br) were recorded and statistically analyzed by paired t-test and one-way analysis of variance at the significance level of alpha =0.05. RESULTS: There was a significant decrease in micro-hardness of enamel in carbamide peroxide bleached groups. However, there was a significant increase in micro-hardness after the remineralization by CPP ACP and the extent of remineralization is more for the Group B. CONCLUSIONS: That bleaching agents reduced enamel micro-hardness and the use of CPP-ACP after bleaching can significantly enhance the micro-hardness of bleached enamel. PMID- 26538924 TI - Comparative evaluation of nickel discharge from brackets in artificial saliva at different time intervals. AB - OBJECTIVES: To determine and compare the potential difference of nickel release from three different orthodontic brackets, in different artificial pH, in different time intervals. MATERIALS AND METHODS: Twenty-seven samples of three different orthodontic brackets were selected and grouped as 1, 2, and 3. Each group was divided into three subgroups depending on the type of orthodontic brackets, salivary pH and the time interval. The Nickel release from each subgroup were analyzed by using inductively coupled plasma-Atomic Emission Spectrophotometer (Perkin Elmer, Optima 2100 DV, USA) model. Quantitative analysis of nickel was performed three times, and the mean value was used as result. ANOVA (F-test) was used to test the significant difference among the groups at 0.05 level of significance (P < 0.05). The descriptive method of statistics was used to calculate the mean, standard deviation, minimum and maximum. SPSS 18 software ((SPSS.Ltd, Quarry bay, Hong Kong, PASW-statistics 18) was used to analyze the study. RESULT: The analysis shows a significant difference between three groups. The study shows that the nickel releases from the recycled stainless steel brackets have the highest at all 4.2 pH except in 120 h. CONCLUSION: The study result shows that the nickel release from the recycled stainless steel brackets is highest. Metal slot ceramic bracket release significantly less nickel. So, recycled stainless steel brackets should not be used for nickel allergic patients. Metal slot ceramic brackets are advisable. PMID- 26538925 TI - The prevalence of mandibular incisive nerve canal and to evaluate its average location and dimension in Indian population. AB - AIM: The aim of this study was to find the prevalence of the mandibular incisive canal, evaluate its location and dimensions using cone beam computer tomography (CBCT) in Indian population. MATERIALS AND METHODS: CBCT scan images of 120 subjects were analyzed for the presence of the mandibular incisive canal, its location, size, and its length. The distance between the incisive canal and the buccal and lingual plate of the alveolar bone, and the distance from the canal to the inferior border of the mandible were also measured to position the canal in the mandible. RESULTS: About 71.66% of the CBCT scans of Indian subjects examined showed the presence of the Incisive canal, of which 48.33% exhibited canals bilaterally and 23.33% showed unilateral canals. 28.33% of the subjects CBCT scans did not exhibit the presence of incisive nerve canal. The average length of the incisive canal was 10.173 mm. The average diameter of the Incisive canal in the CBCT scans was 2.578 mm. The distance from the Inferior border of the mandible to (a) the origin of the Incisive canal was 9.425 mm and (b) to the apex of the Incisive canal was 9.095 mm. The distance from the buccal cortex of the mandible to (a) the origin of the incisive canal was 1.48 mm and (b) to the apex of the incisive canal was 4.476 mm. The distance from the lingual cortex of the mandible to (a) the origin of the incisive canal was 4.464 mm and (b) to the apex of the incisive canal was 5.561 mm. CONCLUSION: The presence, location, and dimensions of the mandibular incisive canal are an additional required data that needs to be elicited before planning an inter-foraminal placement of implants. PMID- 26538926 TI - Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial. AB - AIM: This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. MATERIALS AND METHODS: Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. RESULTS: Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. CONCLUSION: Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality. PMID- 26538927 TI - Efficacy of 2% mepivacaine and 2% lignocaine in the surgical extraction of mesioangular angulated bilaterally impacted third molars: A double-blind, randomized, clinical trial. AB - OBJECTIVE: The purpose of this prospective, randomized, double-blind study was to compare the anesthetic efficacy of 2% mepivacaine and 2% lidocaine (both with 1:80,000 epinephrine) for inferior alveolar nerve block in mesioangular bilaterally impacted third molar extraction. STUDY DESIGN: Forty patients with mesioangular bilaterally impacted third molars were taken for the study; either 2% mepivacaine or 2% lidocaine is given in a double-blind manner. Surgery started 5 min after solution deposition. Success was defined as no or mild discomfort (visual analog scale [VAS] recordings) during the surgical procedure. RESULTS: The mean time for onset period 4.2 min and 4.6 min (P = 0.018). The mean duration anesthesia 177.17 min 166.71 min (P = 0.085). No significant difference between the scores of pain reported by the patients by VAS and venovenous bypass treated with mepivacaine and lidocaine (P = 0.000). Slight increased postoperative analgesics required for mepivacaine group (4.000 tablets) and lidocaine group (4.170 tablets) (P = 0.335). The sharp increase of pulse rate with respect to both the solutions at 5 min after postinjection of local anesthetics. However, there was no statically significant difference in systolic and diastolic blood (P = 0.681) and (P = 0.270). CONCLUSION: Lidocaine and mepivacaine with the same vasoconstrictor have similar action and both solutions are effective in surgical procedures. There were also no significant differences between them in relation to the intensity of postoperative pain. PMID- 26538928 TI - An assessment of coronal leakage of permanent filling materials in endodontically treated teeth: An in vitro study. AB - INTRODUCTION: The present in vitro study was undertaken to evaluate and compare the sealing ability of hybrid composite, glass ionomer cement type II, silver amalgam and Ketac molar as permanent filling material in root canal treated teeth. METHODOLOGY: Hundred maxillary central incisors were selected for the study. After cleaning all the teeth, root canal treatment was carried out on all of them. The crown portion was cut-off at the cervical level. Three millimeter of coronal Gutta-percha was replaced by four different restorative materials. Then after thermocycling, samples were immersed in dye for 2 weeks. The amount of dye penetration was measured using stereomicroscope. Data were collected and analyzed statistically with ANOVA test and Student-Newman-Keuls test. RESULTS: Coronal leakage was seen in all groups. Composite hybrid showed least amount of microleakage as compared to the other three experimental groups, and Ketac molar showed more leakage compared to other experimental groups. CONCLUSION: This study showed that hybrid composites offer better sealing ability compared to other materials tested in this study. PMID- 26538929 TI - Evaluation of shear bond strength between zirconia core and ceramic veneers fabricated by pressing and layering techniques: In vitro study. AB - STATEMENT OF PROBLEM: Although ceramic veneered on to zirconia core have been in use for quite some time, information regarding the comparative evaluation of the Shear bond strength of Pressable & Layered ceramic veneered on to zirconia core is limited. PURPOSE OF STUDY: To evaluate the shear bond strength of zirconia core and ceramic veneer fabricated by two different techniques, Layering (Noritake CZR) and Pressing (Noritake, CZR Press). MATERIALS AND METHOD: 20 samples of zirconia blocks were fabricated and the samples were divided into group A & B. Group A - Ceramic Veneered over zirconia core by pressing using Noritake CZR Press. Group B - Ceramic Veneered over zirconia core by layering using Noritake CZR. The veneered specimens were mounted on to the center of a PVC tube using self-cure acrylic resin leaving 3 mm of the veneered surface exposed as cantilever. Using a Universal testing machine the blocks were loaded up to failure. RESULT: The results were tabulated by using independent samples t-test. The mean shear bond strength for Pressed specimens was 12.458 +/- 1.63(S.D) MPa and for layered specimens was 8.458 +/- 0.845(S.D) MPa. CONCLUSION: Pressed specimens performed significantly better than the layered specimen with a P value 0.001. Clinicians and dental laboratory technicians should consider the use of pressed ceramics as an alternative to traditional layering procedures to reduce the chances of chipping or de-lamination of ceramics. PMID- 26538930 TI - Influence of erbium, chromium-doped: Yttrium scandium-gallium-garnet laser etching and traditional etching systems on depth of resin penetration in enamel: A confocal laser scanning electron microscope study. AB - OBJECTIVE: This study was performed to assess the resin tag length penetration in enamel surface after bonding of brackets to identify which system was most efficient. METHODOLOGY: Our study was based on a more robust confocal microscopy for visualizing the resin tags in enamel. Totally, 100 extracted human first and second premolars have been selected for this study and were randomly divided into ten groups of 10 teeth each. In Group 1, the buccal enamel surface was etched with 37% phosphoric acid (3M ESPE), Group 2 with 37% phosphoric (Ultradent). In Groups 5, 6, and 7, erbium, chromium-doped: Yttrium scandium-gallium-garnet (Er, Cr: YSGG) laser (Biolase) was used for etching the using following specifications: Group 5 (1.5 W/20 Hz, 15 s), Group 6 (2 W/10 Hz, 15 s), and Group 7 (2 W/20 Hz, 15 s). In Groups 8, 9, and 10, Er, Cr: YSGG laser (Biolase) using same specifications and additional to this step, conventional etching on the buccal enamel surface was etched with 37% (3M ESPE) after laser etching. In Groups 1, 5, 6, 7, 8, 9, and 10 3M Unitek Transbond XT primer was mixed with Rhodamine B dye (Sigma-Aldrich, Germany) to etched surface and then cured for 20 s. In Group 2, Ultradents bonding agent was mixed with Rhodamine B. In Group 3, 3M Unitek Transbond PLUS, Monrovia, USA, which was mixed with Rhodamine B dye (Sigma-Aldrich, Germany). Group 4, with self-etching primer (Ultradent-Peak SE, USA) was mixed with Rhodamine B dye (Sigma-Aldrich, Germany). Later (3M Unitek, Transbond XT, Monrovia USA) [Figure 1] was used to bond the modified Begg brackets (T. P. Orthodontics) in Groups 1, 3, 5, 6, 7, 8, 9, and 10. In Groups 2, 4 Ultradent-Peak LC Bond was used to bond the modified brackets. After curing brackets were debonded, and enamel depth penetration was assessed using confocal laser scanning microscope. RESULTS: Group J had a mean maximum depth of penetration of 100.876 MUm, and Group D was the least having a maximum value of 44.254 MUm. CONCLUSIONS: Laser alone groups had comparable depths of penetration to that of self-etching groups but much lower than conventional acid etched groups. PMID- 26538931 TI - Evaluation of clinical parameters to select high prevalence populations for periodontal disease: A cross-sectional study. AB - Epidemiological studies have shown strong evidence that periodontal disease does not affect all subjects in the same manner. OBJECTIVE: There are subjects and sites with higher risk for disease progression. This study tested parameters to select "a priori" sites and subjects potentially at risk. MATERIALS AND METHODS: The data from periodontal clinical examinations of 2273 subjects was used. The clinical loss of attachment was measured in 6 sites per tooth. Using computer software, the patients were distributed into 14 age groups, with intervals of 5 years, from 11 years to greater than 75 years of age. The measure of each site was compared with the average and the median values of the subject age group, with the results indicating site comparative severity (SCS). Three global parameters were calculated: parameter 1 (PI) - percentage of sites with clinical attachment loss > 4 mm; parameter 2 (P2) - percentage of sites with clinical attachment loss j> 7 mm; parameter 3 (P3) - percentage of sites with clinical attachment loss surpassing the median value for the age group by 100% or more. RESULTS: There were 1466 (65%) females and 807 (35%) males. Most subjects had PI, P2 and P3 values less than 30%. Parameter 3 allowed a division of the sample similar to that of Parameters 1 and 2, with the advantage of analyzing the subject in relation to his/her age group. It was suggested that the methodology of SCS is useful for selecting a population with a high disease prevalence, and that cut-off lines between 10% and 20% would be appropriate for using parameter. PMID- 26538932 TI - Antimicrobial effect of herbal dentifrices: An in vitro study. AB - AIM: This study was taken up to compare the antimicrobial effect of few herbal dentifrices against cariogenic organism such as Streptococcus mutans and Lactobacillus acidophilus. MATERIALS AND METHODS: This study was an in vitro model using the well method of microbial culture. Colgate total was used as the positive control and distilled water as the negative control. Dentifrices were prepared in 1:1 dilution using sterile distilled water. The standard strains were inoculated and incubated for 4 h. They were then lawn cultured. Wells were made using a standard template, and the dentifrices were placed in these wells Kruskal Wallis test and Mann-Whitney test were used for statistical analysis. RESULTS: In case of S. mutans, the maximum antimicrobial effect among the six dentifrices was shown by Babool followed by Colgate Herbal. For L. acidophilus, the antimicrobial zone exhibited by all the six dentifrices were similar to the positive control. CONCLUSIONS: Babool and Colgate Herbal have more inhibitory effect against S. mutans than the other dentifrices of the group. Dabur Red, Colgate Herbal, and Himalaya are efficient against L. acidophilus. PMID- 26538933 TI - Assessment of perceptibility and acceptability of color variations between matched teeth among trainee dentist and lay person. AB - AIM: The aim of this study was to find the difference in perceptibility and acceptability of changes done to various color coordinates of matched teeth, between trainee dental surgeons, and lay person. MATERIALS AND METHODS: A photograph with a set of matched central incisor teeth was selected. In one of the central incisors, the color coordinates (hue, value, and chroma) were altered to a preset value. These pictures were presented to trainee dental surgeons and lay person and their level of perception of color change and acceptance of color change was registered and compared. RESULTS: It was found that trainee dental surgeons fared better in perceiving the color change and accepted less of the color changed specimens. The dimension of color that was more discerned both by lay person and trainee dental surgeons was value, hue, and last chroma. CONCLUSION: When compared to a lay person, dental surgeons are more acute in perceiving color changes and do not accept the color difference between teeth to a higher degree. PMID- 26538934 TI - LASER curettage as adjunct to SRP, compared to SRP alone, in patients with periodontitis and controlled type 2 diabetes mellitus: A comparative clinical study. AB - AIM: To compare the effect of scaling and root planning (SRP) alone, and laser curettage as an adjunct to SRP, on the clinical parameters of patients with periodontitis and controlled type 2 diabetes mellitus. MATERIALS AND METHODS: Ten patients were divided into two equal groups in a split-mouth design - Group I: SRP alone, Group II: SRP + laser curettage. The following clinical parameters were recorded: (i) Gingival index (ii) plaque index (iii) sulcular bleeding index (iv) probing depth (PD) and (v) clinical attachment level (CAL). SRP was done in one quadrant using Gracey curettes and in another quadrant SRP plus laser curettage was done. Three weeks after the therapy, the clinical parameters were recorded and the results were analyzed and the percentage of improvement were evaluated. RESULTS: The results of this study indicated that both SRP and SRP + laser curettage were efficient for reducing gingival inflammation and PD. Group II showed more reduction in PD and more gain in CAL than Group I. Mean reduction in PD was 20.22% in Group I and 26.76% in Group II. Mean CAL gain is 32.5% in Group II and 22.34% in Group I. CONCLUSION: In both the groups, gingival inflammation was reduced. When laser curettage was used as adjunct to SRP more reduction in PD and CAL was seen. PMID- 26538935 TI - Prevalence of partial edentulousness among the patients reporting to the Department of Prosthodontics Sri Ramachandra University Chennai, India: An epidemiological study. AB - AIMS AND OBJECTIVES: To determine the occurrence of various missing teeth pattern among the partial edentulous patients residing in Chennai who are undergoing treatment for the replacement of missing teeth in the Department of Prosthodontics, Sri Ramachandra University Chennai, India. SETTINGS AND DESIGN: Study was undertaken from January 2014 to October 2014, and the design was a descriptive cross-sectional study. MATERIALS AND METHODS: Five hundred and sixty one persons aged between 13 and 87 years (267 males and 294 females) were selected, intraoral examination was done visually and results were recorded on specially designed clinical examination forms. STATISTICAL ANALYSIS: Data were analyzed using statistics SPSS 19.0 version (IBM India Private Limited Bangalore) to investigate the relationship between quantitative variables. RESULTS: The results showed the patients with Kennedy's Class III were found to be the most prevalent among all the groups (55%). The most common modification in all the groups was Class III modification I (26%). It was also found that Kennedy's Class III was founded more in the age group of 31-40 with 54.4% in the maxillary arch and 47.2% in the mandibular arch. CONCLUSION: The findings of this study show that the Kennedy's Class III was the most commonly occurring and were found to be more predominant in the younger group of population. PMID- 26538936 TI - The effect of cigarette smoking on the severity of periodontal diseases among adults of Kothamangalam Town, Kerala. AB - AIMS AND OBJECTIVES: Smoking is one of the major risk factors for periodontal disease. This study aims at examining the difference in the periodontal status of current smokers, former smokers, and nonsmokers among the adults of Kothamangalam, Kerala. It investigates the association between the level of cigarette consumption and periodontal attachment loss taking into account the effect of age, gender, and oral hygiene. METHODOLOGY: The study population consisted of 30 subjects and divided into three groups as current, former, and nonsmokers with periodontal disease. All clinical parameters were recorded. Smoking assessment was done using a self-reported questionnaire, and statistical analysis was carried out. RESULTS: Current smokers had a higher percentage of sites with mean probing depth, and greater mean clinical attachment level than former smokers and nonsmoker. A significant difference (P < 0.05) was found in clinical attachment loss (CAL) between Group I (current smokers) and III (nonsmokers), that shows the increased risk of current smokers for future periodontal destruction. The CAL for current smokers was 5.20 +/- 2.440 and for the nonsmokers was 1.50 +/- 1.265. A significant difference (P < 0.05) was found in CAL between Group I and III. SUMMARY AND CONCLUSION: The study revealed a marked association between cigarette smoking and the risk of periodontitis. The increased destruction among current smokers showed a dose-dependent relationship with the amount of cigarette consumption. For former smokers, the duration since quitting smoking was associated with a lower risk for severe periodontitis. PMID- 26538937 TI - Association of matrix metalloproteinase 1 gene promoter mutation and residual ridge resorption in edentulous patients of South Indian origin. AB - BACKGROUND: Matrix metalloproteinase (MMP) are involved in bone transformation at the extraction site postdental extraction. We examined the genetic association between single nucleotide polymorphisms of MMP-1 and continuous atrophy of edentulous mandible. METHODS: Buccal cells from 33 edentulous patients were collected using sterile wooden spatula and were suspended in 15 ml falcon tubes containing 1.5 ml of cell lysis buffer, without proteinase K. The cells were transported to the laboratory on ice and were stored at -20 degrees C until being processed. RESULTS: Of the samples analyzed, 26 edentulous patients (78.8%) carried 2G allele, while 7 of them (21.2%) carried 1G allele. CONCLUSION: The patients with the alveolar bone resorption exhibited more of 2G allele while only 21.2% of them showed 1G allele, associated with excessive atrophy of edentulous mandible. This study may provide genetic background to identify susceptible individuals prone to develop jawbone atrophy after dental extraction. PMID- 26538938 TI - Periodontal risk calculator versus periodontal risk assessment. AB - INTRODUCTION: The purpose of study was twofold: To determine the extent of inter valuator and inter group variation in risk scores assigned to study subjects by PRC and PRA. To explore the relationship between risk scores assigned by PRC and using the PRA. MATERIALS AND METHODS: 57 patients (33 male patients and 24 Female patients between 20 and 65 years age group) were assessed with PRC and PRA tools during their first visit. RESULTS AND CONCLUSION: We entered the resulting information in to the PRC and PRA to obtained a riskscore for each subject at first visit. The chi-square test significance between PRC and PRA is < 0.05 indicatesthe accuracy of the both tools. PMID- 26538940 TI - Knowledge and attitude toward human immunodeficiency virus/acquired immuno deficiency syndrome among dental and medical undergraduate students. AB - BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV) is a major public health challenge. Unjustified calls for the isolation of patients with HIV infection might further constrain the potential for expansion of clinical services to deal with a greater number of such patients. This infectious illness can evoke irrational emotions and fears in health care providers. Keeping this in view, a study was conducted to assess the knowledge and attitudes related to HIV/acquired immune deficiency syndrome (AIDS) among dental and medical students. METHODOLOGY: Descriptive cross-sectional survey of the entire dental and medical undergraduate students from two colleges was carried out using a pretested, self administered questionnaire. Descriptive statistics such as percentage was used to present the data. RESULTS: Ninety-eight percentage medical and dental undergraduate graduate students knew about HIV transmission in the hospital. Journals and internet were the leading source of information among both medical and dental undergraduates. The majority of respondents discussed HIV-related issues with their classmates. Surprisingly, 38% medical and 52% dental undergraduates think that HIV patient should be quarantined (isolation) to prevent the spread of infection. 68% medical and 60% dental undergraduates are willing to rendering dental/medical care to HIV-infected patients. Relatively large proportion (98%) of participants was willing to participate for HIV prevention program. CONCLUSION: The knowledge of medical and dental students is adequate, but the attitude needs improvement. Dental and medical students constitute a useful public health education resource. Comprehensive training, continuing education, and motivation will improve their knowledge and attitude, which enable them to provide better care to HIV patients. PMID- 26538939 TI - Comparative analysis of gingival crevicular fluid beta-glucuronidase levels in health, chronic gingivitis and chronic periodontitis. AB - BACKGROUND AND OBJECTIVES: Current methods available for periodontal disease diagnosis are seriously deficient in terms of accuracy, in the ability to predict ongoing or future disease activity and indeed in determining whether previously diseased sites are in an arrested phase or still active. One area that is receiving a great deal of attention is the biochemical investigation of gingival crevicular fluid (GCF). beta-glucuronidase (betaG) is one of the enzymes found in GCF that is involved in degradation of the ground substance and fibrillar components of host connective tissue. GCF betaG activity might be a good indicator or predictor of periodontal disease activity. This study was conducted to estimate and compare the GCF betaG levels in patients with healthy periodontium, chronic gingivitis, and chronic periodontitis. METHODOLOGY: Subjects were classified into three groups of 20 patients each; healthy individuals, chronic gingivitis, and chronic periodontitis. After recording the plaque index, gingival index and probing pocket depth, 1 MUL GCF was collected by placing a calibrated microcapillary pipette extracrevicularly and transferred to sterile plastic vials containing 350 MUL of normal saline with 1% bovine serum albumin. Analysis of betaG was done by spectrophotometry. RESULTS: betaG levels in GCF were significantly higher in chronic periodontitis group (mean value - 2.04743), followed by chronic gingivitis group (mean - 1.11510) and healthy group (0.53643). CONCLUSION: Increased betaG levels were observed in patients with increased periodontal destruction, hence GCF betaG levels can be used as biochemical marker for periodontal disease activity. PMID- 26538941 TI - Evaluation of transcription factor that regulates T helper 17 and regulatory T cells function in periodontal health and disease. AB - BACKGROUND: The differentiation of naomicronve T helper (Th) cells towards Th17 and regulatory T cells (Treg) is regulated by the transcription factors retinoic acid related orphan receptor gamma transcription (RORYt) and Forkhead box p3 (Foxp3), respectively. An imbalance in the activity of these transcription factors could result in the dysregulation of Th17/Treg response. MATERIALS AND METHODS: Total RNA was isolated from gingival tissue obtained from 10 patients, each from periodontally healthy and diseased groups. The gene expression of RORYt and Foxp3 was measured by real-time reverse transcription polymerization chain reaction using total RNA isolates from gingival tissues group when compared to the healthy group, while Foxp3 demonstrated a 6.68 +/- 0.03 fold decrease of expression in diseased group when compared to healthy group. CONCLUSION: Our results indicate a functional imbalance in the Th17/Treg response in periodontal disease group when compared to the periodontally healthy group. PMID- 26538942 TI - Acupuncture - An effective tool in the management of gag reflex. AB - Gagging is of great concern to the dentist as it is a serious impediment during the execution of various dental procedures. The etiology of gagging is multifactorial, and several suggestions have been offered to arrest this reflex, some of which are nonsustainable and does not show the immediate result. Acupuncture has been successfully employed as an adjunct to local anesthesia in dental extractions, pain management and also in the symptomatic management of temporomandibular joint disorders. The author highlights the application of acupuncture in the management of patients with gag reflex during dental procedures and its benefits are reported. PMID- 26538943 TI - A study to evaluate cephalometric hard tissue profile of Tamil population for orthognathic surgery. AB - The primary aim of this study is to compare, the cephalometric hard tissue profile values and analysis between Tamil and Caucasian population. The study also aims to create a better understanding in the facial proportions of Tamil Nadu population and to have better diagnosis and treatment planning for orthognathic surgery for Tamil population in Tamil Nadu. PMID- 26538944 TI - Management of severe sleep apnea secondary to juvenile arthritis with temporomandibular joint replacement and mandibular advancement. AB - Variations affecting the growth centers can severely affect the normal formation and subsequent function of vital musculoskeletal structures. We report a case of bilateral condylar atrophy with a history of juvenile arthritis (JA) resulting in progressive obstructive sleep apnea (OSA) in adulthood. In addition to this, the case report emphasizes the role of temporomandibular joint replacement and advancement of the mandible to correct progressive OSA secondary to idiopathic JA. Computed tomography revealed micrognathia, condylar hypoplasia, and decreased pharyngeal airway space. The resultant increase in the retrolingual-pharyngeal airway space following the surgery, helped to completely resolve the presenting symptoms. It is hoped that the described technique could be used in similar cases with a predictable outcome. PMID- 26538945 TI - Cleft rhinoplasty. AB - It is universally accepted that correction of cleft lip nose deformity remains a formidable challenge for any cleft surgeon. The nose is a prominent part of the face, and hence a masterly executed cleft lip repair directs the beholders' eyes from the deformed lip to the deformed nose. A deformed nose that results from unilateral cleft of the lip and palate is likened to a tent whose one side is depressed. Many investigators believe that the deformity of the nose is produced by the malpositioning of essentially normal structures, on the other hand some cleft surgeons contend that it is the intrinsic defects in nasal structures that result in cleft nasal deformity. Depressed and hypoplastic bony scaffolding is the most important aspect of cleft nose deformity and addressing this aspect of cleft nose deformity is the secret of success of a perfect secondary rhinoplasty. Controversy still exists on timing of cleft nasal deformity. Proponents of delayed nasal repair suggest that altering the cartilages in early nasal repair at the time of lip repair would complicate future corrective nasal surgeries if the primary repair would prove unsatisfactory. The correction of nasal deformity could be performed with closed or open technique. This paper highlights one such challenging unilateral cleft lip nasal deformity in a adult patient treated by secondary rhinoplasty by open technique. PMID- 26538946 TI - A comparison of efficiency of biopolymer and allograft matrix with autogenous gingival graft used in root coverage procedure. AB - Severe surgical techniques have been introduced to augment gingival tissue dimensions like the free gingival graft, free connective grafts, etc., However, both the techniques are associated with significant patient morbidity due to the secondary surgical site. In order to overcome these postsurgical complications, acellular dermal allografts have been used as a substitute for the palatal donor tissue yielding clinically comparable results. However, the cost and origin of the material raises concern regarding the frequent use of the material. As an improved alternative to above-mentioned graft material, the use of platelet-rich fibrin (PRF) and collagen matrices has been promoted in the recent past. The objective of this illustrative case report is to test the efficacy of collagen matrix, PRF to augment attached gingiva and to assess the esthetic outcome when compared to the standard treatment with free autogenous graft. PMID- 26538947 TI - Cracked tooth syndrome: A report of three cases. AB - Cracked tooth syndrome (CTS), the term was coined by Cameron in 1964, which refers to an incomplete fracture of a vital posterior tooth extending to the dentin and occasionally into the pulp. CTS has always been a nightmare to the patient because of its unpredictable symptoms and a diagnostic dilemma for the dental practitioner due to its variable, bizarre clinical presentation. The treatment planning and management of CTS has also given problems and challenges the dentist as there is no specific treatment option. The management of CTS varies from one case to another or from one tooth to another in the same individual based on the severity of the symptoms and depth of tooth structure involved. After all, the prognosis of such tooth is still questionable and requires continuous evaluation. This article aims at presenting a series three cases of CTS with an overview on the clinical presentation, diagnosis and the different treatment options that varies from one case to another. PMID- 26538948 TI - Dental rehabilitation of a child with early childhood caries using Groper's appliance. AB - The mainstay of pediatric dental practice is the successful esthetic rehabilitation of a preschooler with advanced carious lesions. Loss of masticatory efficiency, compromised esthesis, mispronunciation of labiodentals sounds, and development of abnormal oral habits are compromises arising due to the loss of primary anterior teeth at an early age either due to trauma or due to caries. Parental desire is the most decisive factor for the placement of an anterior esthetic appliance. This unique case report highlights the fabrication of simple, Groper's appliance in a 5-year-old child with early childhood caries. PMID- 26538949 TI - Platysma myocutaneous flap for reconstruction of intraoral defects following excision of oral sub mucous fibrosis: A report of 10 cases. AB - Various surgical procedures are available for treating oral submucous fibrosis, but all of them have their inherent drawbacks. The superiorly based platysma myocutaneous flap is a common reconstruction option for intraoral defects followed after excision of fibrous bands in oral submucous fibrosis. The superiorly based flap has an excellent blood supply, but less efficient venous drainage when compared with posteriorly based flap. We present our results of using a superiorly based flap in the treatment of oral submucous fibrosis. Of 10 patients eight had no postoperative complications, one patient developed partial skin loss and other developed venous congestion which was managed conservatively. PMID- 26538950 TI - Management of invasive cervical resorption in a maxillary central incisor. AB - Invasive cervical resorption is often not diagnosed properly, leading to improper treatment or unnecessary loss of the tooth structure. Early diagnosis and appropriate treatment are the keys to a successful outcome of therapy. Invasive cervical resorption is often seen in the cervical area of the tooth, but because it is initiated apical to the epithelial attachment, it can present anywhere in the root. In the early stages, it may be symmetrical, but larger lesions have the tendency to be asymmetrical. It can expand apically or coronally. PMID- 26538951 TI - Surgical management of a large cleft palate in a Pierre Robin sequence: A case report and review of literature. AB - Pierre Robin syndrome or Pierre Robin sequence (PRS) is a congenital etiologically heterogeneous condition presenting with various malformations. Here we are reporting the surgical management of an 18-month-old female baby who was referred from Department of Pediatrics with a complaint of a large cleft palate. She was taken up for palatoplasty with consent for elective tracheostomy. After genetic evaluation, the authors conclude that the presented case was a PRS in isolation with mild cardiac anomalies and an inferiorly placed hypoplastic epiglottis. Patient should be followed up and growth modifications of the jaws should be done. PMID- 26538952 TI - Biological post. AB - Anterior tooth fracture as a result of traumatic injuries, is frequently encountered in endodontic practice. Proper reconstruction of extensively damaged teeth can be achieved through the fragment reattachment procedure known as "biological restoration." This case report refers to the esthetics and functional recovery of extensively damaged maxillary central incisor through the preparation and adhesive cementation of "biological post" in a young patient. Biological post obtained through extracted teeth from another individual-represent a low-cost option and alternative technique for the morphofunctional recovery of extensively damaged anterior teeth. PMID- 26538953 TI - Osseous choristoma of the labial mucosa: A rare case report. AB - Osseous choristoma is a normal bone tissue in an ectopic position. These are slow growing lesions that are usually completely asymptomatic and only present when there is a disruption in the function of the organ due to its large size as it grows. Definitive diagnosis is obtained only after the histopathological examination. The etiology remains still questionable. The treatment of choice is surgical excision. Here we report a case of choristoma in the lower labial mucosa in a 47-year-old female. PMID- 26538954 TI - Management of horizontally impacted dilacerated lateral incisor. AB - Impaction of maxillary lateral incisor with odontome and retained deciduous tooth is not often seen in regular dental practice. Impaction of anterior teeth cause generalized spacing which affects the esthetics of the face. Here we report a case of an 18-year-old patient with horizontally impacted dilacerated lateral incisor, which was bought into occlusion with the help of orthodontic tooth movement within a span of 18 months. PMID- 26538955 TI - Oral mucocele: Review of literature and a case report. AB - Mucocele is the most common lesion of the oral mucosa, which results from the accumulation of mucous secretion due to trauma and lip biting habits or alteration of minor salivary glands. Mostly they are two types based on histological features which as follows: Extravasation and retention. Mucoceles can appear at anywhere in the oral mucosa such as lip, cheeks and the floor of the mouth, but mainly appear in the lip. Diagnosis is mostly based on clinical findings. The most common location of the extravasation mucocele is the lower lip. Mucoceles most probably affect young patients but can affect all the age groups. They may have a soft consistency, bluish, and transparent cystic swelling, history of bursting and collapsing due to which resolves themselves then refilling which may be repeated. The treatment of choice is surgical removal of the mucocele. PMID- 26538956 TI - Treatment of gingival recession using free gingival graft with fibrin fibronectin sealing system: A novel approach. AB - Periodontal plastic surgery is the branch of periodontology that is focused mainly on the correction or elimination of mucogingival problems associated with lack of attached gingiva, a shallow vestibule and aberrant frenum. Various mucogingival surgical procedures are used to halt the progression of the gingival recession and to correct poor esthetic appearance. Free gingival autograft is one of the most common techniques used for a gingival recession in areas of inadequate attached gingiva in the mandibular anterior region. Fibrin sealants are human plasma derivatives that mimic the final stages of blood coagulation, forming a fibrin clot. Fibrin Sealants enhances the overall outcome of surgical intervention because of their hemostatic, adhesive, and healing properties. These properties of fibrin sealants may reduce operating time, prevent complications, and enhance the overall outcome of many surgical interventions. Hence, this case report aims to investigate the clinical effectiveness of free gingival graft along with the commercially available fibrin-fibronectin sealing system (Tissucol((r))) in the treatment of Miller's class II gingival recession. PMID- 26538957 TI - Prosthetic management of malpositioned implant using custom cast abutment. AB - Two cases are reported with malpositioned implants. Both the implants were placed 6-7 months back. They had osseointegrated well with the surrounding bone. However, they presented severe facial inclination. Case I was restored with custom cast abutment with an auto polymerizing acrylic gingival veneer. Case II was restored with custom cast UCLA type plastic implant abutment. Ceramic was directly fired on the custom cast abutments. The dual treatment strategy resulted in functional and esthetic restorations despite facial malposition of the implants. PMID- 26538958 TI - Root canal treatment of a maxillary first premolar with three roots. AB - Successful root canal treatment needs a thorough knowledge of both internal and external anatomy of a tooth. Variations in root canal anatomy constitute an impressive challenge to the successful completion of endodontic treatment. Undetected extra roots and canals are a major reason for failed root canal treatment. Three separate roots in a maxillary first premolar have a very low incidence of 0.5-6%. Three rooted premolars are anatomically similar to molars and are sometimes called "small molars or radiculous molars." This article explains the diagnosis and endodontic management of a three rooted maxillary premolar with separate canals in each root highlighting that statistics may indicate a low incidence of abnormal variations in root canal morphology of a tooth, but aberrant anatomy is a possibility in any tooth. Hence, modern diagnostics like cone beam computed tomography, and endodontic operating microscope may have to be used more for predictable endodontic treatment. PMID- 26538959 TI - The orthodontic management of ectopic canine. AB - The canines being the cornerstone of the arch and smile is one of the teeth, which has the longest eruption passage that gets influenced by local and general etiological factors easily. The initial calcification of the crowns starts at 4-5 months of age and proceeds toward eruption about 11-13 years of age with mesiobuccal crown angulation that gets corrected toward occlusion. It gets displaced buccally or palatally or may sometimes get impacted. Early intervention is the best suited to manage canine eruption patterns. Once erupted ectopically, they possess a great challenge in repositioning them back into their correct position. This case report discusses an orthodontic treatment planning and execution to correct a buccally placed canine with an anterior crossbite in an adult. PMID- 26538960 TI - Cyst or tumor in the buccomaxillary region: Review of literature and a case report. AB - Odontogenic tumors (OTs) include entities of a hamartomatous nature, such as odontoma, benign neoplasms like an adenomatoid odontogenic tumor (AOT), some benign neoplasms are aggressive as in the case of ameloblastoma. The AOT is a rare odontogenic tumor constituting only 3% of all the OT and very often misdiagnosed as an odontogenic cyst. We report a case of an intra-osseous type of AOT occurred in a young 16-year-old female located in the anterior maxilla along with the clinical, radiological, histological features, and literature review related to the tumor affecting the patient. PMID- 26538961 TI - Stevens-Johnson syndrome induced by a combination of lamotrigine and valproic acid. AB - Lamotrigine and valproic acid are well-tolerated anticonvulsants, but frequently associated with severe cutaneous reactions, such as the Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis, when used in combination. We report a case of SJS likely induced by the use of a lamotrigine and valproic acid regimen and as a dental surgeon it is important to identify such lesion and report to pharmacovigilance. PMID- 26538962 TI - Odontogenic myxoma of maxilla: A rare presentation in an elderly female. AB - Odontogenic myxomas are rare benign neoplasm of mesenchymal origin, comprising 3 6% of all odontogenic tumors. They are slow growing, non-metastasizing, often asymptomatic with local aggressiveness due to its infiltrative nature and hence high recurrence rate, with a high incidence of occurrence in the mandible. Most frequently occurs in second to third decade of life, seldom occurs beyond these age groups. Hereby, we present a case of odontogenic myxoma occurring in the maxilla in a 65-year-old female managed by partial maxillectomy. PMID- 26538963 TI - Multiple myeloma involving mandible: In an elderly female. AB - Multiple myeloma (MM) is a malignancy of plasma cell origin. It often has a multicentric origin within the bone. It makes about 1% of all malignancies and 15% of all hematologic malignancies. There is a monoclonal proliferation of abnormal plasma cells in this disease that arise from a single malignant precursor that has undergone uncontrolled mitotic division. These cells in turn produce one type of immunoglobulin light chain, either kappa or lambda. Unifocal, monoclonal proliferation of plasma cells is called plasmacytoma. Hereby, we present a case of a 65-year-old female patient who presented with a swelling of the mandible. The uniform sheets of plasma cells in the histopathology punched out radiolucencies in skull radiograph and the blood picture of anemia and hypercalcemia, confirmed the case as MM. PMID- 26538964 TI - Bleaching of fluorosis stains using sodium hypochlorite. AB - Fluorosis staining is commonly considered an esthetic problem because of the psychological impact of unesthetic maxillary anterior teeth. Numerous treatment approaches have been proposed, ranging from bleaching to enamel reduction to restorative techniques. Bleaching of hypomineralized enamel lesions, using 5% sodium hypochlorite, has been useful clinically. The technique described, in this case, appears to have advantages over other methods for improving the appearance of fluorotic lesions. It is simple, low cost, noninvasive, so the enamel keeps its structure, relatively rapid, and safe; it requires no special materials, and it can be used with safety on young permanent teeth. PMID- 26538965 TI - Crown lengthening procedure in the management of amelogenesis imperfecta. AB - Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta. PMID- 26538966 TI - A rare case of mumps orchitis. AB - Mumps is a relatively mild short-term viral infection of the salivary glands that usually occurs during childhood. Meningitis/encephalitis is a well-known complication of mumps, but involvement and infection of the testis in adolescent boys and adult men are rare. We report a case of an 18-year-old male patient with mumps associated epididymo-orchitis on the left side. The diagnosis was confirmed clinically and serologically by IgG and IgM titers. The symptoms were resolved after the administration of anti-inflammatory and pain medications with bed rest and ice packs applied to the area. PMID- 26538967 TI - Rehabilitation of Bell's palsy patient with complete dentures. AB - Facial nerve disorders may be of sudden onset and more often of unknown etiology. Edema of the facial nerve within the fallopian canal results in Bell's palsy. This causes compression of the nerve and affects the microcirculation. Many authors have suggested treatment for facial nerve paralysis ranging from simple physiotherapy to complicated microvascular decompression. It more often results in symptoms like synkinesis and muscle spasm after the decompression surgery of the nerve because of the inability to arrange the nerve fibers within the canal. The treatment choice also depends on patient's age, extent of the nerve damage, and patient's needs and desires. Many patients who cannot be rehabilitated functionally can be treated for esthetics of the involved muscles. This case report elaborates about a patient who was rehabilitated for esthetics and to some extent for function. PMID- 26538968 TI - Myoepithelioma. AB - Myoepithelioma is a benign salivary gland tumor in the head and neck region, accounting for 1-1.5% of all glandular tumors. The diagnosis is rendered histopathologically, and it includes the proliferation of myoepithelial cells, without chondroid or myxochondroid stroma and ductal components (up to 5% of ductal component is acceptable). In our case report, this lesion has occurred in a 46-year-old female patient, and presented as well defined, nodular growth on the right posterior palatal region. Bony erosion and invasion were observed radiographically, and the lesion was excised surgically, with 1-2 cm of clear margin. The microscopic features included proliferating tumor sheets, composed of bland looking spindle and plasmacytoid shaped myoepithelial cells, and few cells showed clear cytoplasm, which were confirmed immunohistochemically as myoepithelial cells. Thus, the final diagnosis of benign myoepithelioma was rendered and no recurrence had been reported so far in the regular follow-up. PMID- 26538969 TI - A simple method of enhancing retention in interim hollow bulb obturator in a case of an acquired palatal defect. AB - Maxillary defects occur either as a result of surgical resection of malignant tumors of the nasal cavity and paranasal sinuses or of the congenital causes. Rehabilitation of the patients with maxillectomy defects presents a challenge in restoring the lost form, function and speech. Maxillary interim obturators in prosthetic reconstruction of the defects are often complicated with lack of adequate retention, stability, and support. This case report presents the simplified approach, to rehabilitate a case of sub-total maxillectomy due to squamous cell carcinoma of maxillary sinus, using a closed hollow bulb obturator prosthesis fabricated with a "U" loop and a modified buccal flange for enhanced retention of the prosthesis. PMID- 26538970 TI - Comparative evaluation of depigmentation techniques in split-mouth design with electrocautery and laser. AB - Excessive gingival pigmentation is a major esthetic concern for many people. Melanin pigmentation is known to be caused by melanin granules within the gingival epithelium. Smile is determined not only by the shape, the position, and the color of the teeth, but also by the gingival tissues. Gingival health and appearance are essential components of an attractive smile. It is not a medical problem, but it feels unesthetic for the patient and particularly in patients having a very high lip/smile line. Depigmentation is not a clinical indication but a treatment of choice where esthetics is a concern and is desired by the patient. For depigmentation of gingival, different treatment modalities have been reported such as bur abrasion, scraping, partial thickness flap, cryotherapy, electrosurgery, and laser. The present case series describes two simple and effective surgical depigmentation techniques treated with diode laser and electrosurgery. PMID- 26538971 TI - Disto-angular transmigrated impacted mandibular molar with enostosis: A rare intraoral lesion. AB - A 29-year-old male patient reported for replacement of missing teeth. The patient gave history of unerupted right lower posterior teeth and the orthopantomogram revealed transmigrated mandibular second molar to the inferior border of mandible just below the root apices of second premolar associated with enostosis distally toward the ramus of mandible with size of about 21 mm Chi 20 mm. This rare interosseous defect plays a vital role in deciding prosthetic treatment options for missing teeth and utmost care should be taken to preserve the health of the patient during such procedures. PMID- 26538972 TI - Lip repositioning surgery for correction of excessive gingival display. AB - Esthetic demands have considerably increased over the years in routine clinical practice. A pleasant smile can give supreme confidence to an individuals personality. However, a perfect smile is dictated by a perfect balance of the white (teeth) and pink (gingival) display. This balance can be managed different treatment modalities, which is based on proper diagnosis. This case report demonstrates a successful management of gummy smile with a lip-repositioning procedure in a patient with an incompetent upper lip. This was accomplished by removing a partial thickness strip of mucosa from the maxillary buccal vestibule and suturing the lip mucosa to the mucogingival line. This resulted in a narrower vestibule and restricted muscle pull, thereby resulting incompetent lips and reduced gingival display during smiling. PMID- 26538973 TI - A case report of granular cell ameloblastoma associated with aneurysmal bone cyst like features. AB - Granular cell ameloblastoma is a rare variant of ameloblastoma, which is histopathologically characterized by the presence of large eosinophilic granular cells within the ameloblastic follicle. Its accurate preoperative diagnosis is based upon clinical, radiological, and incisional biopsy findings. This article reports a case of granular cell ameloblastoma in a 65-year-old female, which on incisional biopsy showed the features suggestive of aneurysmal bone cyst. Furthermore, the influence of macroscopic presentation of the current lesion on its accurate preoperative incisional biopsy diagnosis is discussed in detail. PMID- 26538974 TI - Ghost teeth: Regional odontodysplasia of maxillary first molar associated with eruption disorders in a 10-year-old girl. AB - Regional odontodysplasia (RO) is an uncommon, developmental anomaly of the dental hard tissues that affects ectodermal and mesodermal dental components with characteristic clinical and radiographic findings. Clinically, RO affects a particular segment in either or both dentitions in the maxilla or mandible or both jaws. Radiographic features have consistently demonstrated thin and defective layers of enamel and dentine, resulting in a faint, fuzzy outline, creating a ghost-like appearance. The RO etiology is uncertain; numerous factors have been suggested and considered as local trauma, irradiation, hypophosphatasia, hypocalcemia, hyperpyrexia. A case of RO in a 10-year-old girl whose chief complaint were forwardly placed upper front teeth and the absence of eruption of permanent teeth. Clinical and radiographic features are described. PMID- 26538975 TI - A telescopic retainer prosthesis in full mouth rehabilitation. AB - The use of questionable abutments has been made possible by modifying the design of the prosthesis. Telescopic retainers help to retain a prosthesis on a tilted and malaligned abutments. PMID- 26538976 TI - A noble method of using intravenous infusion set as a stent in localized lower posterior vestibuloplasty: A technical note. AB - Vestibuloplasty is the procedure for shallow vestibule, prior to the prosthesis. Usually, vestibuloplasty is carried out in patients with completely edentulous arches. There are multiple techniques of vestibuloplasty described in the review of literature. However, it has not been emphasized on isolated shallow vestibule. This article describes our experience in the isolated or localized vestibuloplasty for a partially edentulous individual with a shallow vestibule pertaining to a single missing tooth. PMID- 26538977 TI - Complicated canal morphology of mandibular first premolar. AB - The aim of this article was to report an unusual anatomic variation of mandibular first premolar, with one root and three distinct canals, which leave pulp chamber and merge short of apex to exit as two separate apical foramina. The incidence of three canals existing as two apical foramina has only been documented in the literature by a few case reports. To achieve successful endodontic treatment, the clinician has to identify the different canal configurations and treat them properly. PMID- 26538978 TI - Human immunodeficiency virus induced oral candidiasis. AB - Human immunodeficiency virus (HIV) infection is a worldwide health problem, which affects in both developing and developed countries. The oral lesions caused due to this disease can drastically change the life of the patient, in terms of quality. We can also know the progression of the disease and also the important immune status of the patient. Lots of information on HIV is known in the developed countries and very less reports are available in the developing countries. The morbidity of HIV disease is due to its association with opportunistic fungal infection and the most common among them is oral candidiasis. Here, we present a case report on an apparently healthy male patient of 39 years, who had oral candidiasis and was one of the indicators for HIV infection. PMID- 26538979 TI - Interdental papilla regeneration around implants: A novel window technique (2 years follow-up). AB - Reconstructing predictable and esthetic papilla is the most complex and challenging aspect of implant dentistry. To obtain an esthetic and predictable gingival architecture and implant restoration, interdental papilla plays an important role. The main objective of the surgeon during the second stage of implant treatment should be the creation of interdental papilla prior to prosthetic restoration. The aim of this case report was to demonstrate a novel window technique for developing predictable and esthetic papilla around dental implants, which was followed for 2 years with excellent esthetic results. PMID- 26538980 TI - Peri-implant soft tissue management: A case report (2 years follow-up) (Patrick Palacci technique revisited). AB - Peri-implant plastic surgery aims at improving the esthetic aspects of smile and masticatory function. Over the years, several techniques such as tissue punch technique, full thickness flaps, and scalloping adjustment of flaps around implants have been employed; it was very difficult to achieve a papilla like formation around implants. These added time and expense of the final results and led to undesirable complications. In order to overcome these difficulties, this case report describes a surgical technique where in papilla like formation and increase in width of attached gingiva around implants can be achieved with a single surgical procedure. PMID- 26538981 TI - A rare presentation of a simple bone cyst. AB - Simple bone cyst is an oft-described entity, which goes by many sobriquets and has been presented in the literature as early as 1926. It is a lesion of unclear etiology with many proposed hypothesis for its pathogenesis and nonspecific histopathological presentation. We present a case of a solitary bone cyst, which clinically presented as a solitary lesion, but radiological examination revealed multiple lesions peppering the maxilla and the mandible, thereby highlighting the importance of atypical presentation and "surprise" lesions that may show up on radiological examination. PMID- 26538982 TI - Drug-induced thrombocytopenic purpura. AB - Drug-induced thrombocytopenic purpura is a skin condition result from a low platelet count due to drug-induced anti-platelet antibodies caused by drugs. Drug induced thrombocytopenic purpura should be suspected when a patient, child or adult, has sudden, severe thrombocytopenia. Drug-induced thrombocytopenic purpura is even more strongly suspected when a patient has repeated episodes of sudden, severe thrombocytopenia. PMID- 26538983 TI - Sealing ability of lateral condensation, thermoplasticized gutta-percha and flowable gutta-percha obturation techniques: A comparative in vitro study: Retraction. AB - [This retracts the article on p. S131 in vol. 4, PMID: 23066233.]. PMID- 26538984 TI - Fertility at midlife. PMID- 26538985 TI - Menopausal hormone therapy and ovarian cancer. PMID- 26538986 TI - Overview of research studies on osteoporosis in menopausal women since the last decade. AB - PURPOSE/INTRODUCTION: Osteoporosis is a multifactorial and slowly emerging global health problem. The lifetime risk of dying from hip fracture is same as that from breast cancer. One out of three women between age group of 50-60 years in India suffers from osteoporosis. Indian women have an early age of onset of osteoporosis as compared to western counterparts. There is need for early diagnosis, identification of high-risk groups and prevention and treatment of osteoporosis in the Indian context. The aim of this study was to review the literature published in last decade and compare the research in India with that in rest of the world. MATERIALS AND METHODS: Research articles with key words menopausal, osteoporosis and bone mineral density were searched in Pubmed from January 2004 to December 2013. Articles were categorized according to year, place and objective of the studies. RESULTS: In India more articles were published in year 2010-11 (53.3%), while outside the country a uniform distribution of studies was observed throughout the last decade. Objective of research was screening and diagnosis (36.7%) and risk factor identification (40%) in most of the Indian studies as compared to rest of the world. Research publications on prevention and treatment of osteoporosis are less in India (20%). CONCLUSION: Research focusing on diagnosis, prognosis, prevention and treatment are needed in India. PMID- 26538987 TI - Low vitamin D, and bone mineral density with depressive symptoms burden in menopausal and postmenopausal women. AB - BACKGROUND: The reported association between vitamin D level and loss of Bone mineral densitometry measurements (BMD) has been controversial. OBJECTIVE: The objective of the current study was to determine whether low vitamin D level and BMD are associated with depresive symptoms as burden in Arab women during the menopausal and postmenopausal period. DESIGN AND SETTING: A cross-sectional descriptive study design was used at the Primary Health Care (PHC) Centers in Qatar. SUBJECTS: A multi-stage sampling design was used and a representative sample of 1436 women aged 45-65 years were included during July 2012 and November 2013 and 1106 women agreed to participate (77.2%) and responded to the study. MATERIALS AND METHODS: BMD (g/m(2)) was assessed at the BMD unit using a Lunar Prodigy DXA system (Lunar Corp., Madison, WI). The antero-posterior lumbar spine (L2-L4) and the mean of the proximal right and left femur were be measured by two technician and then reviewed by one radiologist. Data on body mass index (BMI), clinical biochemistry variables including serum 25-hydroxyvitamin D were collected. The Beck Depression Inventory (BDI) was administered for depression purposes. RESULTS: Of the 1436 women living in urban and rural areas, 1106 women agreed to participate (77.0%) and responded to the study. The mean age and standard deviation of the subjects was 53.8 +/- 3.2. The median age of natural menopausal in the present study was 49 years (mean and standard deviation 49.5 +/ 3.1 and postmenopausal was 58.1 +/- 3.3). There were statistically significant differences between menopausal stages with regards to ethnicity, education level, systolic and dialostic blood pressure, parity, sheesha smoking and depressive symptoms. Overall 30.4% of women were affected with osteopenia/osteoporosis in premenopausal and postmenopausal (24.4% vs 35.7%; P = 0.0442). Osteopenia in premenopausal and postmenopausal (18.7% vs 29.3%; P = 0.030) and Osteoporosis (9.9% vs 15.9%; P = 0.049) were significantly higher in post-menopausal women than in premenopausal women (P = 0.046). Similarly, vitamin D deficiency was more prevalent among postmenopausal women than menopausal women. Overall, only 15.1% of women had optimum vitamin D level and 15.5% had severe, 33.2% had moderate vitamin D insufficiency and 36.3% had mild vitamin D insufficiency in menopausal and post menopausal women (P = 0.021). The study revealed that vitamin D level, hemoglobin level, serum iron fasting plasma glucose, calcium, triglycerides, high density lipid (HDL) cholesterol, low density lipid (LDL) Cholesterol, alkaline phosphate and magnesium were considerably lower in postmenopausal compared to menopausal women (P < 0.001). CONCLUSION: The current study revealed that there was a strong association between vitamin D level and BMD in Arab women during the menopausal and post-menopausal period. PMID- 26538988 TI - A retrospective analysis of dermatoses in the perimenopausal population attending a tertiary care centre in South India. AB - INTRODUCTION: Menopausal is a normal physiologic aging process in women characterized by decreasing estrogen levels. The skin is an organ dependant on hormones, estrogen being the most important in case of females, thereby influencing both the biology of skin and composition. Studies show that the systemic effects of estrogen deprivation occur years after attaining menopausal, however cutaneous features have been noticed earlier. The purpose of this study is to evaluate the common disorders occurring in perimenopausal women of Indian ethnicity. MATERIALS AND METHODS: A retrospective observational study of outpatient records from Dermatology clinic between 2005 and 2012. All female patients between 45-55 years of age from an outpatient register that outlines the final diagnosis made by a qualified dermatologist after investigations. The data was entered according to the pattern of dermatoses and their seasonal variation and analyzed were included. RESULTS: A total of 8,156 cases were found. After analysis of the many variables, the most common dermatoses in the perimenopausal population were eczematous disorders (23.6%), followed by urticaria (12.4%) and papulosquamous disorders (10.7%). Of the eczematous disorders, allergic and photosensitive disorders were found to be more frequent. CONCLUSION: The leading dermatoses being eczema and urticaria in the perimenopausal population probably accounts for a tendency of exaggerated response to external factors. The population studied in the current study might be of significance due to complete lack of treatment in the form of hormone replacement therapy (HRT), while routine sun exposure and cultural practices predominate. However, evaluation with respect to individual factors is beyond the scope of the current study and may be necessary to define a causal relationship. PMID- 26538989 TI - Endometriosis presenting as carcinoma colon in a perimenopausal woman. AB - Endometriosis is a common benign disease of reproductive age women, and can involve the intestinal tract. Inconsistent clinical presentation, similar features on radiological imaging and colonoscopy with other inflammatory and malignant lesions of the bowel makes the preoperative diagnosis of bowel endometriosis difficult. We present a case of a 42-year-old perimenopausal female clinically presented, investigated and managed in the lines of carcinoma of sigmoid colon. She underwent terminal ileac resection with end to end anastomoses, Hartmann's procedure and total hysterectomy with bilateral salpingoophorectomy. The histopathological report revealed endometriosis of small intestine, large intestine, mesentery, right ovary and adenomyoma of uterus. Thus, bowel endometriosis should also be considered as differential diagnosis in reproductive age women with gastrointestinal symptoms or intestinal mass of uncertain diagnosis. PMID- 26538990 TI - A rare case of occult abdominal tuberculosis with Poncet's disease mimicking Adult onset Still's disease. AB - A 50-year-old female presented with fever, symmetrical arthralgias, rash, painful oral ulcerations and alopecia since 8 weeks. Examination showed mild hepatospleenomegaly. Investigations revealed leucocytosis, neutrophilia, elevated sedimentation rate and raised ferritin levels (3850 ng/ml). Computerized tomography (CT) abdomen showed hepatospleenomegaly, mild ascitis and mild bilateral pleural-effusion. After ruling out occult infections, tuberculosis, malignancies and autoimmune diseases by appropriate investigations, and due to raised ferritin levels, adult onset stills disease (AOSD) was diagnosed. Patient responded to oral steroids initially, but after 7 days developed severe abdominal pain. Repeat CT showed multiple enlarged, necrotic and matted retroperitoneal lymph nodes with caseating granuloma on histopathology suggesting tuberculosis. Patient was given four-drug anti-tubercular treatment and she improved. Thus our patient of occult abdominal tuberculosis with reactive arthritis (Poncet's disease) presented with hyperferritinemia mimicking AOSD. We postulate that extreme hyperferritinemia can be seen in tuberculosis and tuberculosis must be conclusively ruled out before diagnosing AOSD in tropics. PMID- 26538991 TI - Upper gastrointestinal bleed in a post menopausal woman due to combination of high first dose aspirin and clopidogrel prescribed for acute coronary syndrome. AB - Combination of aspirin, clopidogrel and enoxaparin remains the standard treatment for acute coronary syndrome (ACS) but is known to increase the incidence of upper gastrointestinal bleed (UGIB). We hereby report an unusual case of gastrointestinal bleed (GIB) as it resulted inspite of proton pump inhibitor (PPI) prophylaxis within the second day of treatment in a post-menopausal woman (PMW) with high first dose of aspirin clopidogrel dual combination in a patient of ACS. PMID- 26538992 TI - Elderly female with Autoimmune hemolytic anemia. AB - Autoimmune hemolytic anemia (AIHA) is a rare disease with an estimated prevalence of around 17/100,000. It is often difficult to diagnose and treat AIHA, especially in elderly. A 60-year-old female was admitted with the complaints of low grade fever, on-off for 6 months, progressive fatigue and dyspnea on exertion. She was transfused with three units of blood within these 6 months. Examination revealed pallor, edema, hemic murmur, and palpable liver. Hb was 2.9 gm%, T Bil 5.2 mg/dl, ESR 160 mm, and reticulocyte count 44.05%. Direct Coombs test was positive, anti-nuclear antibody (ANA) and Anti ds DNA were positive. A diagnosis of systemic lupus erythematosus (SLE) with AIHA was considered and patient was transfused with two units of packed red cells and put on steroid (prednisolone) at 1 mg/kg body weight daily. After 3 weeks, her Hb had increased to 10.4 gm% with gross clinical improvement. PMID- 26538993 TI - Isolated renal hydatid cyst in a diabetic postmenopausal female. AB - Isolated renal hydatid disease is very uncommon and is usually an unexpected disclosure during radiological imaging. Since it affects the kidney, renal mass, or colic, hematuria, pyuria, and dysuria are the predominant symptoms. We present a case of a 48-year-old diabetic postmenopausal female incidentally diagnosed with an isolated giant renal hydatid cyst while evaluating the cause of recurrent flank pain. PMID- 26538994 TI - Common mistakes done by authors in conduct and reporting risk factor (observational) studies. PMID- 26538995 TI - Critical Care In Korea: Present and Future. AB - Critical (or intensive) care medicine (CCM) is a branch of medicine concerned with the care of patients with potentially reversible life-threatening conditions. Numerous studies have demonstrated that adequate staffing is of crucial importance for patient outcome. Adequate staffing also showed favorable cost-effectiveness in terms of ICU stay, decreased use of resources, and lower re admission rates. The current status of CCM of our country is not comparable to that of advanced countries. The global pandemic episodes in the past decade showed that our society is not well prepared for severe illnesses or mass casualty. To improve CCM in Korea, reimbursement of the government must be amended such that referral hospitals can hire sufficient number of qualified intensivists and nurses. For the government to address these urgent issues, public awareness of the role of CCM is also required. PMID- 26538996 TI - Preserving the Integrity of Citations and References by All Stakeholders of Science Communication. AB - Citations to scholarly items are building bricks for multidisciplinary science communication. Citation analyses are currently influencing individual career advancement and ranking of academic and research institutions worldwide. This article overviews the involvement of scientific authors, reviewers, editors, publishers, indexers, and learned associations in the citing and referencing to preserve the integrity of science communication. Authors are responsible for thorough bibliographic searches to select relevant references for their articles, comprehend main points, and cite them in an ethical way. Reviewers and editors may perform additional searches and recommend missing essential references. Publishers, in turn, are in a position to instruct their authors over the citations and references, provide tools for validation of references, and open access to bibliographies. Publicly available reference lists bear important information about the novelty and relatedness of the scholarly items with the published literature. Few editorial associations have dealt with the issue of citations and properly managed references. As a prime example, the International Committee of Medical Journal Editors (ICMJE) issued in December 2014 an updated set of recommendations on the need for citing primary literature and avoiding unethical references, which are applicable to the global scientific community. With the exponential growth of literature and related references, it is critically important to define functions of all stakeholders of science communication in curbing the issue of irrational and unethical citations and thereby improve the quality and indexability of scholarly journals. PMID- 26538997 TI - Development of Quality Management Systems for Clinical Practice Guidelines in Korea. AB - This study introduces the Clinical practice guidelines (CPGs) appraisal system by the Korean Academy of Medical Sciences (KAMS). Quality management policies for CPGs vary among different countries, which have their own cultures and health care systems. However, supporting developers in guideline development and appraisals using standardized tools are common practices. KAMS, an organization representing the various medical societies of Korea, has been striving to establish a quality management system for CPGs, and has established a CPGs quality management system that reflects the characteristics of the Korean healthcare environment and the needs of its users. KAMS created a foundation for the development of CPGs, set up an independent appraisal organization, enacted regulations related to the appraisals, and trained appraisers. These efforts could enhance the ability of each individual medical society to develop CPGs, to increase the quality of the CPGs, and to ultimately improve the quality of the information available to decision-makers. PMID- 26538998 TI - The Association between Body Weight Misperception and Psychosocial Factors in Korean Adult Women Less than 65 Years Old with Normal Weight. AB - With society's increasing interest in weight control and body weight, we investigated the association between psychological factors and body image misperception in different age groups of adult Korean women with a normal weight. On a total of 4,600 women from the Korea National Health and Nutrition Examination Survey 2007-2009, a self-report questionnaire was used to assess body weight perception and 3 psychological factors: self-rated health status, stress recognition, and depressed mood. Through logistic regression analysis, a poor self-rated health status (P = 0.001) and a higher recognition of stress (P = 0.001) were significantly associated with body image misperception and this significance remained after controlling for several sociodemographic (Model 1: adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.31-2.00), health behavior and psychological factors (Model 2: aOR, 1.59; 95% CI, 1.29-1.96; Model 3: aOR, 1.36; 95% CI, 1.01-1.84). Especially, highly stressed middle-aged (50-64 yr) women were more likely to have body image misperception (Model 2: aOR, 2.85; 95% CI, 1.30-6.26). However, the correlation between depressed mood and self reported body weight was inconsistent between different age groups. In conclusion, self-rated health status and a high recognition rate of severe stress were related to body weight misperception which could suggest tailored intervention to adult women especially women in younger age or low self-rated health status or a high recognition rate of severe stress. PMID- 26538999 TI - Correlation between Drug Market Withdrawals and Socioeconomic, Health, and Welfare Indicators Worldwide. AB - The relationship between the number of withdrawn/restricted drugs and socioeconomic, health, and welfare indicators were investigated in a comprehensive review of drug regulation information in the United Nations (UN) countries. A total of of 362 drugs were withdrawn and 248 were restricted during 1950-2010, corresponding to rates of 12.02 +/- 13.07 and 5.77 +/- 8.69 (mean +/- SD), respectively, among 94 UN countries. A socioeconomic, health, and welfare analysis was performed for 33 OECD countries for which data were available regarding withdrawn/restricted drugs. The gross domestic product (GDP) per capita, GDP per hour worked, health expenditure per GDP, and elderly population rate were positively correlated with the numbers of withdrawn and restricted drugs (P < 0.05), while the out-of-pocket health expenditure payment rate was negatively correlated. The number of restricted drugs was also correlated with the rate of drug-related deaths (P < 0.05). The World Bank data cross-validated the findings of 33 OECD countries. The lists of withdrawn/restricted drugs showed markedly poor international agreement between them (Fleiss's kappa = -0.114). Twenty-seven drugs that had been withdrawn internationally by manufacturers are still available in some countries. The wide variation in the numbers of drug withdrawals and restrictions among countries indicates the need to improve drug surveillance systems and regulatory communication networks. PMID- 26539000 TI - Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation. AB - Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, >= moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results. PMID- 26539001 TI - Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy. AB - In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea. PMID- 26539002 TI - Effects of Methotrexate on Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis. AB - The purpose of this study was to evaluate the effects of rheumatoid arthritis (RA) and antirheumatic drugs on atherosclerosis by comparing carotid intima-media thickness (CIMT) as an indicator for cardiovascular diseases (CVD). This study included 44 female RA patients who met the 2010 ACR/EULAR criteria and age matched 22 healthy females. CIMT was measured on both carotid arteries using a B mode ultrasound scan. The mean value of both sides was taken as the CIMT of the subject. The CIMT was evaluated according to the use of drugs, disease activity and CVD risk factors in RA patients as a case-control study. Higher CIMT was observed in RA patients as compared with healthy subjects (0.705 +/- 0.198 mm, 0.611 +/- 0.093 mm, respectively, P < 0.05). With adjustment for the CVD risk factors, disease activity and the use of anti-rheumatic drugs, methotrexate (MTX) only showed a favorable effect on CIMT in RA. A significantly lower CIMT was observed in RA with MTX as compared with RA without MTX (0.644 +/- 0.136 mm, 0.767 +/- 0.233 mm, respectively, P < 0.05). The effects were correlated with MTX dosage (beta = -0.029, P < 0.01). The use of MTX should be considered in high priority not only to control arthritis but also to reduce the RA-related CVD risk to mortality. PMID- 26539003 TI - Validation of the Effectiveness and Safety of Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas: 10-year Experience of a Single Institution. AB - This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis. PMID- 26539004 TI - Assessment of Breast Cancer Patients' Knowledge and Decisional Conflict Regarding Tamoxifen Use. AB - Breast cancer is the most common type of female cancer. Tamoxifen, a selective estrogen receptor modulator, is widely used to decrease breast cancer recurrence and mortality among patients. However, it also increases the risk of endometrial cancer. This study aimed to assess knowledge and decisional conflict regarding tamoxifen use. Between June and October 2014, breast cancer patients using tamoxifen were consecutively screened and requested to complete a survey including the EQ-5D, Satisfaction with Decision Scale (SWD), Decisional Conflict Scale (DCS), and a self-developed, 15-item questionnaire measuring tamoxifen related knowledge. The study sample comprised 299 patients. The mean total knowledge score was 63.4 of a possible 100.0 (range, 13.3-93.3). While 73.9% of the participants knew that tamoxifen reduces the risk of breast cancer recurrence, only 57.9% knew that the drug increases endometrial cancer risk. A higher education level (>= college) was associated with a higher, total knowledge score (beta = 4.291; P = 0.017). A higher knowledge score was associated with a decreased DCS score (beta = -0.366; P < 0.001). A higher SWD score was also associated with decreased decisional conflict (beta = -0.178; P < 0.001). In conclusion, the breast cancer patients with higher levels of tamoxifen-related knowledge showed lower levels of decisional conflict regarding tamoxifen use. Clinicians should provide the exact information about tamoxifen treatment to patients, based on knowledge assessment results, so as to aid patients' decision making with minimal conflict. PMID- 26539005 TI - Application of New Cholesterol Guidelines to the Korean Adult Diabetic Patients. AB - The American College of Cardiology and the American Heart Association (ACC/AHA) 2013 joint guidelines for the treatment of hypercholesterolemia expand the indications for statin therapy. This study was performed to estimate the numbers of diabetic patients indicated for statin therapy according to the Third Adult Treatment Panel (ATP-III) of the National Cholesterol Education Program guidelines and the new ACC/AHA guidelines in Korea. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012. Patients with diabetes over 30 yr of age were analyzed by the two guidelines. Of the total 1,975 diabetic patients, only 377 (19.1%) were receiving drugs for dyslipidemia. Among 1,598 patients who had not taken any medications for dyslipidemia, 65.6% would be indicated for statin therapy according to the ATP III guidelines. When we apply the new guidelines, 94.3% would be eligible for statin therapy. Among the total diabetic patients, the new guidelines, compared with the ATP-III guidelines, increase the number eligible for statin therapy from 53.1% to 76.2%. The new guidelines would increase the indication for statin therapy for most diabetic patients. At present, many diabetic patients do not receive appropriate statin therapy. Therefore efforts should be made to develop the Korean guidelines and to ensure that more diabetic patients receive appropriate statin therapy. PMID- 26539006 TI - Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels. AB - Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-naive, HBV related, compensated cirrhosis patients with elevated HBV DNA levels (>= 2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal (< 40 U/L, n = 364) and elevated group (>= 40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels. PMID- 26539007 TI - Epidemiology and Regional Distribution of Pediatric Unintentional Emergency Injury in Korea from 2010 to 2011. AB - Injury is a leading cause of death and disability in children and adolescents worldwide. The purpose of the current study was to investigate the epidemiologic characteristics of the pediatric unintentional injuries presenting to the Korean emergency department (ED). We included unintentional injuries in patients aged < 20 yr. Data collected from January 2010 to December 2011 was extracted from the National Emergency Department Information System (NEDIS) of Korea. The NEDIS data included information on patient's age and gender, geographic location of the ED visits, mechanism of injuries; and clinical outcomes. Most (94.1%) injuries were unintentional while 5.9% were intentional. The rate of ED visit for pediatric unintentional injury was 6,097 per 100,000 and critical injury was 59.8 per 100,000 (< 20 yr habitants). The mortality rate was 5.4 per 100,000. The mortality rate of pediatric unintentional injuries was 0.1% including the prehospital death and ED death. Unintentional pediatric injuries occurred most commonly in those age 0-4 boys and girls and were predominantly caused by collisions. Male motorcyclists aged 15-19 yr formed a critical injury high-risk group. The rates of critical injury and mortality were highest in Jeju, Gangwon, Gwangju, and Jeonbuk than those in other regions. High-risk groups by age, gender, mechanism and region should be targeted to prevent pediatric injuries in Korea. PMID- 26539008 TI - Is Radical Perineal Prostatectomy a Viable Therapeutic Option for Intermediate- and High-risk Prostate Cancer? AB - The aim of this study was to investigate a single-institution experience with radical perineal prostatectomy (RPP), radical retropubic prostatectomy (RRP) and minimally invasive radical prostatectomy (MIRP) with respect to onco-surgical outcomes in patients with intermediate-risk (IR; PSA 10-20 ng/mL, biopsy Gleason score bGS 7 or cT2b-2c) and high-risk (HR; PSA > 20 ng/mL, bGS >= 8, or >= cT3) prostate cancer (PCa). We retrospectively reviewed data from 2,581 men who underwent radical prostatectomy for IR and HR PCa (RPP, n = 689; RRP, n = 402; MIRP, n = 1,490 [laparoscopic, n = 206; robot-assisted laparoscopic, n = 1,284]). The proportion of HR PCa was 40.3%, 46.8%, and 49.5% in RPP, RRP, and MIRP (P < 0.001), respectively. The positive surgical margin rate was 23.8%, 26.1%, and 18.7% (P = 0.002) overall, 17.5%, 17.8%, and 8.8% (P < 0.001) for pT2 disease and 41.9%, 44.4%, and 40.0% (P = 0.55) for pT3 disease in men undergoing RPP, RRP, and MIRP, respectively. Biochemical recurrence-free survival rates among RPP, RRP, and MIRP were 73.0%, 70.1%, and 76.8%, respectively, at 5 yr (RPP vs. RPP, P = 0.02; RPP vs. MIRP, P = 0.23). Furthermore, comparable 5-yr metastases-free survival rates were demonstrated for specific surgical approaches (RPP vs. RPP, P = 0.26; RPP vs. MIRP, P = 0.06). RPP achieved acceptable oncological control for IR and HR PCa. PMID- 26539009 TI - Geographic Distribution of Urologists in Korea, 2007 to 2012. AB - The adequacy of the urologist work force in Korea has never been investigated. This study investigated the geographic distribution of urologists in Korea. County level data from the National Health Insurance Service and National Statistical Office was analyzed in this ecological study. Urologist density was defined by the number of urologists per 100,000 individuals. National patterns of urologist density were mapped graphically at the county level using GIS software. To control the time sequence, regression analysis with fitted line plot was conducted. The difference of distribution of urologist density was analyzed by ANCOVA. Urologists density showed an uneven distribution according to county characteristics (metropolitan cities vs. nonmetropolitan cities vs. rural areas; mean square=102.329, P<0.001) and also according to year (mean square=9.747, P=0.048). Regression analysis between metropolitan and non-metropolitan cities showed significant difference in the change of urologists per year (P=0.019). Metropolitan cities vs. rural areas and non-metropolitan cities vs. rural areas showed no differences. Among the factors, the presence of training hospitals was the affecting factor for the uneven distribution of urologist density (P<0.001). Uneven distribution of urologists in Korea likely originated from the relatively low urologist density in rural areas. However, considering the time sequencing data from 2007 to 2012, there was a difference between the increase of urologist density in metropolitan and non-metropolitan cities. PMID- 26539010 TI - Depression and Its Severity Are Strongly Associated with Both Storage and Voiding Lower Urinary Tract Symptoms Independently of Prostate Volume. AB - Depression is related to various functional medical conditions. Its association with lower urinary tract symptoms (LUTS) is also expected. We evaluated whether depression and its severity are associated with LUTS when LUTS risk factors including prostate volume (PV) are taken into account in a large population of Korean men. Study subjects included 10,275 men who underwent routine health check ups at the Healthcare System Gangnam Center of Seoul National University Hospital. Depression was assessed using Beck Depression Inventory-II and LUTS using international prostate symptom score. PV was measured using transrectal ultrasonography by a radiologist. Effect sizes of depression severity on total, storage, and voiding symptoms were assessed. In multivariate logistic regression analysis, mild, moderate and severe depression were associated with total (adjusted odds ratio: aOR = 2.99, 3.86 and 8.99; all P < 0.001), voiding (aOR = 3.04, 3.28 and 5.58; all P < 0.001) and storage symptoms (aOR = 2.43, 3.43 and 2.89; all P < 0.05) showing dose response relationships (all P trend < 0.001). In a subgroup analysis for participants with PV data (n = 1,925), mild and moderate severe depression were also associated with LUTS (aOR = 3.29, 2.84; P < 0.001 and 0.018, respectively). In conclusion, depression and its severity are strongly associated with total, voiding, and storage symptoms independently of PV state. PMID- 26539011 TI - Gray and White Matter Degenerations in Subjective Memory Impairment: Comparisons with Normal Controls and Mild Cognitive Impairment. AB - Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes. PMID- 26539012 TI - Gender Differences in Depressive Symptom Profile: Results from Nationwide General Population Surveys in Korea. AB - This study investigated gender differences in symptom profiles of major depressive disorder (MDD) in the Korean general population. Data were pooled from the series of nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001, 2006 and 2011, respectively. Of the 18,807 participants, 507 (397 women and 110 men) were diagnosed with MDD within the prior 12 months. In agreement with previous studies, women with MDD appeared to be more vulnerable to experiencing atypical depressive episodes defined as depression with two or more symptoms of fatigue, increased appetite and hypersomnia (P < 0.001). In terms of individual symptoms, female gender was significantly related with higher prevalence of fatigue (P = 0.008), hypersomnia (P = 0.001), noticeable psychomotor retardation (P = 0.029) and suicidal attempts (P = 0.016) with adjustment for birth cohort effect, partner status, and employment status. In the same analysis, men with MDD appeared more vulnerable to decreased libido than women (P = 0.009). This is the first report to demonstrate gender differences in symptomatology of MDD in the general Korean population, and the results are comparable to previous investigations from western societies. Assumingly, the intercultural similarity in female preponderance to atypical depression might reflect the common biological construct underlying the gender difference in mechanism of MDD. In clinical settings, gender differences of MDD should be carefully considered, because these features could be related with treatment response and drug side effects. PMID- 26539013 TI - The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates. AB - Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered. PMID- 26539014 TI - Steep Decrease of Gender Difference in DSM-IV Alcohol Use Disorder: A Comparison of Two Nation-wide Surveys Conducted 10 Years Apart in Korea. AB - While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35 5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions. PMID- 26539015 TI - Implication of Sarcopenia and Sarcopenic Obesity on Lung Function in Healthy Elderly: Using Korean National Health and Nutrition Examination Survey. AB - Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index >= 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age. PMID- 26539016 TI - Reproducibility of Apparent Diffusion Coefficient Measurements in Malignant Breast Masses. AB - This study aimed to evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in malignant breast masses, and to determine the influence of mammographic parenchymal density on this reproducibility. Sixty-six patients with magnetic resonance findings of the mass were included. Two breast radiologists measured the ADC of the malignant breast mass and the same area on the contralateral normal breast in each patient twice. The effects of mammographic parenchymal density, histology, and lesion size on reproducibility were also assessed. There was no significant difference in the mean ADC between repeated measurements in malignant breast masses and normal breast tissue. The overall reproducibility of ADC measurements was good in both. The 95% limits of agreement for repeated ADCs were approximately 30.2%-33.4% of the mean. ADC measurements in malignant breast masses were highly reproducible irrespective of mass size, histologic subtype, or coexistence of microcalcifications; however, the measurements tended to be less reproducible in malignant breast masses with extremely dense parenchymal backgrounds. ADC measurements in malignant breast masses are highly reproducible; however, mammographic parenchymal density can potentially influence this reproducibility. PMID- 26539017 TI - Acute Cholecystitis in Patients with Scrub Typhus. AB - Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain. PMID- 26539020 TI - Uncertainty and Its Consequences in Clinical Practice. PMID- 26539018 TI - Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015. AB - Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases. PMID- 26539019 TI - Two-stage Surgery for an Aortoesophageal Fistula Caused by Tuberculous Esophagitis. AB - An aortoesophageal fistula (AEF) is an extremely rare, potentially fatal condition, and aortic surgery is usually performed together with extracorporeal circulation. However, this surgical method has a high rate of surgical complications and mortality. This report describes an AEF caused by tuberculous esophagitis that was treated successfully using a two-stage operation. A 52-yr old man was admitted to the hospital with severe hematemesis and syncope. Based on the computed tomography and diagnostic endoscopic findings, he was diagnosed with an AEF and initially underwent thoracic endovascular aortic repair. Esophageal reconstruction was performed after controlling the mediastinal inflammation. The patient suffered postoperative anastomotic leakage, which was treated by an endoscopic procedure, and the patient was discharged without any further problems. The patient received 9 months of anti-tuberculosis treatment after he was diagnosed with histologically confirmed tuberculous esophagitis; subsequently, he was followed as an outpatient and has had no recurrence of the tuberculosis or any further issues. PMID- 26539021 TI - Clothes Do Not Make the Man: Well-favored Figures are Game-changers in the Biomedical Publication. PMID- 26539022 TI - An Exploration of Family and Juvenile Justice Systems to Reduce Youth HIV/STI Risk. AB - Using in-depth interviews with 20 probation youth (60% female; 35% white; 30% Hispanic; mean age 15years, range=13-17), their caregivers (100% female; mean age 44years, range=34-71) and 12 female probation officers (100% white; mean age 46years, range=34-57), we explored how family and probation systems exacerbate or mitigate sexual risk. We conducted thematic analyses of interviews, comparing narratives of families of sexually risky (n=9) versus non-sexually risky (n=11) youth. Family functioning differed by youth sexual risk behavior around quality of relationships, communication, and limit-setting and monitoring. The involvement of families of sexually risky youth in probation positively influenced family functioning. Data suggest these families are amenable to intervention and may benefit from family-based HIV/STI interventions delivered in tandem with probation. PMID- 26539023 TI - copCAR: A Flexible Regression Model for Areal Data. AB - Non-Gaussian spatial data are common in many fields. When fitting regressions for such data, one needs to account for spatial dependence to ensure reliable inference for the regression coefficients. The two most commonly used regression models for spatially aggregated data are the automodel and the areal generalized linear mixed model (GLMM). These models induce spatial dependence in different ways but share the smoothing approach, which is intuitive but problematic. This article develops a new regression model for areal data. The new model is called copCAR because it is copula-based and employs the areal GLMM's conditional autoregression (CAR). copCAR overcomes many of the drawbacks of the automodel and the areal GLMM. Specifically, copCAR (1) is flexible and intuitive, (2) permits positive spatial dependence for all types of data, (3) permits efficient computation, and (4) provides reliable spatial regression inference and information about dependence strength. An implementation is provided by R package copCAR, which is available from the Comprehensive R Archive Network, and supplementary materials are available online. PMID- 26539024 TI - Predictors of Childhood Depressed Mood: A Two-Generational Study. AB - This study tests a model of intergenerational influences on childhood depressed mood that proposes (1) indirect and direct paths from maternal drug use to offspring depressed mood; and (2) pathways from maternal maladaptive personality attributes to offspring depressed mood via adverse child-rearing practices. A cross-sectional two-generational design is employed. Data was obtained utilizing structured questionnaires administered by trained interviewers in the homes of the participants. The sample was comprised of African American and Puerto Rican children (N=210) and their mothers living in New York City. Using structural equation modeling, the analysis showed that maladaptive personality attributes are associated with adverse maternal child-rearing practices, which, in turn, are related to depressed mood in the offspring. Maternal drug use had a direct effect on offspring depressed mood. Maternal drug use also had an indirect path to offspring depressed mood via maladaptive personality attributes and adverse maternal child-rearing practices. The total effects analysis indicated that adverse maternal child-rearing practices was the strongest predictor of childhood depressed mood. This finding was consistent with the proximal position of the latent construct within the model. Maternal personality attributes and drug use were of lesser importance, but still statistically significant. The results suggest that maternal drug use and maladaptive personality attributes pose risks for the future depressive mood of children. The relative strength of maternal involvement with offspring should be the focus of preventive and therapeutic intervention efforts. PMID- 26539025 TI - Practicability confirmation by meta-analysis of intravitreal ranibizumab compared to photodynamic therapy to treat polypoidal choroidal vasculopathy. AB - PURPOSE: The literatures show that photodynamic therapy (PDT) and intravitreal ranibizumab (IVR) have their own specific advantages in treating polypoidal choroidal vasculopathy (PCV). Using a meta-analysis, we want to provide some suggestions for the clinical application of the two treatments to PCV patients through a comparison of the functional outcomes in a follow-up period after administration. METHODS: A comprehensive literature search was performed using several databases to assemble the controlled trials of IVR and PDT. The program of RevMan version 5.0 was used to analyze the data. The effects of two treatments on PCV were evaluated by comparing weighted mean differences (WMDs) in the change of LogMar visual acuity, central retinal thickness (CRT), and the deterioration ratio for the proportions of patients with visual reductions from the baseline. Data with homogeneity among studies were analyzed using a fixed-effect meta analysis model; otherwise, a random-effect model was applied to data with heterogeneity. RESULTS: Five studies are included covering 260 cases in total in this study. The outcomes of IVR treatment compared to PDT appear to significantly improve vision, decrease the central retinal thickness (CRT), and reduce the invalidation rate. The LogMar visual acuity shifts from 0.6 to 0.3 in the following 24 months and the improvement rate of visual acuity ranges from 60-70% in IVR treated patients. However, the visual acuity improvement is moderate in the PDT group. These analyses indicate that IVR is an applicable treatment in PCV patients, although PDT is able to yield about a 35% visual acuity improvement in a short-term follow-up. Our 3-D mesh modal also confirms that IVR is able to yield better effects to treat PCV than PDT. CONCLUSIONS: The analysis in this study suggests that IVR has a significant effect on the improvement of visual acuity when treating patients with PCV. Our findings clearly document that IVR can be used as a more effective therapy for long-term administration in PCV. PMID- 26539026 TI - KCC2 expression supersedes NKCC1 in mature fiber cells in mouse and rabbit lenses. AB - PURPOSE: Na-K-Cl cotransporter 1 (NKCC1) and K-Cl cotransporter 2 (KCC2) have fundamental roles in neuron differentiation that are integrated with gamma aminobutyric acid (GABA) and glutamate receptors, GABA synthesized by GAD25/65/67 encoded by GAD1/GAD2 genes, and GABA transporters (GATs). Cells in the eye lens express at least 13 GABA receptor subunits, alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) and N-methyl D-aspartate (NMDA) glutamate receptors, GAD1/GAD2, GAT1-4 and vGAT, and NKCC1. NKCC1:KCC2 ratios determine the switch in GABA actions from trophic/growth promoting early in development to their classic inhibitory roles in adult neurons. Lens epithelial cells cover the anterior surface and differentiate to elongated fiber cells in the lens interior with comparable morphology and sub-cellular structures as neurons. NKCC1 is expressed before KCC2 in neuron development and increases cell chloride, which stimulates differentiation and process formation. Subsequently, KCC2 increases and extrudes cell chloride linked with maturation. KCC2 has an additional structural moonlighting role interacting with F-actin scaffolding in dendritic spine morphogenesis. We examined KCC2 versus NKCC1 spatial expression in relation to fiber cell developmental status within the lens. METHODS: Immunofluorescence and immunoblots were used to detect expression in mouse and rabbit lenses. RESULTS: NKCC1 was restricted to peripheral elongating lens fiber cells in young adult mouse and rabbit lenses. Lens KCC2 expression included the major KCC2b neuronal isoform and was detected in interior fiber cells with decreased NKCC1 expression and localized at the membranes. Lens expression of RE-1 silencing transcription factor (REST) regulated KCC2 is consistent with GAD1 and GAD2, several GABA and glutamate receptor subunits, miR-124, and other REST-regulated genes expressed in lenses. CONCLUSIONS: NKCC1 in peripheral elongating fiber cells is superseded by KCC2 expression in interior mature fiber cells that also express >20 additional integral GABA biology genes, AMPA/NMDA glutamate receptors, and an array of accessory proteins that together underlie morphogenesis in neurons. The present findings provide further evidence that this fundamental neuronal regulation is extensively conserved in lens and identify additional parallels in the morphogenetic programs that underlie lens fiber cell and neuronal differentiation and contribute to the development of visual acuity. PMID- 26539027 TI - Human tear analysis with miniaturized multiplex cytokine assay on "wall-less" 96 well plate. AB - PURPOSE: Tears are a particularly limited body fluid and commonly used in the diagnosis of patients who have ocular diseases. A popular method for analysis of ocular inflammation in tears uses Luminex(r) bead multiplex technology to generate valuable multiple cytokine profile outputs with 25-50 ul tear sample volume. We propose a method for measuring tear cytokines with 5 MUl tear sample volume and 80% reduced Luminex reagents compared to previous protocols. METHODS: Using human tears pooled from 1,000 participants, the DA-Bead-based method running at 5-20 ul volume, using manual pipetting, in conjunction with a magnetic Luminex cytokine (four-plex) panel assay in a 96-well format was performed and validated for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, and IL-6. RESULTS: Upon use of the DA-Bead method at the 5 MUl volume with cytokine standards, the concentrations of each of the four cytokines were found to be linear over a range of 3.5-4 log pg/ml with an intra assay coefficient of variation (CV) <=5%, inter-assay %CV <=10%, and accuracy within the 70-130% range. Upon use of a 5 ul healthy pooled tear sample, cytokine concentrations were detected with a precision intra-assay %CV ? 20% for IL-6, IFN gamma, or TNF-alpha or 30.37% with IL-1beta. The inter-assay %CV with tears was <=20.84% for all cytokines. Tear volumes run at 5 MUl on DA-Bead produced a similar cytokine expression profile at a 1-month interval and were highly correlated with the larger 10 MUl-based tear sample volume cytokine profile with R(2) = 0.98. CONCLUSIONS: DA-Bead assay is highly sensitive and reproducible and has a performance profile that is potentially suitable for use in standard clinical scenarios. Considering the use of as little as 5 ul of assay beads and 5 ul sample, this is also likely to reduce the assay cost significantly and ease diagnosis of patients with ocular diseases. PMID- 26539028 TI - TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients. AB - PURPOSE: Elevated intraocular pressure (IOP) is the only known modifiable risk factor for primary open angle glaucoma (POAG), and it can be caused by reduced aqueous humor outflow from the anterior chamber. Outflow is predominantly regulated by the trabecular meshwork, consisting of specialized cells within a complex extracellular matrix (ECM). An imbalance between ECM-degrading matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) within the trabecular meshwork is thought to contribute to POAG. This study aimed to quantify levels of TIMPs and MMPs in aqueous humor samples from glaucomatous and non-glaucomatous eyes, analyze MMP/TIMP ratios, and correlate results with age, IOP, and Humphrey's visual field pattern standard deviation (PSD). METHODS: Aqueous humor samples were collected from 26 non-glaucomatous control subjects before cataract surgery and 23 POAG patients undergoing trabeculectomy or cataract surgery. Analyte concentrations were measured using multiplexed immunoassays. Statistical significance was assessed with Mann-Whitney U tests, and Spearman's method was used to assess correlations with age, IOP, and PSD. RESULTS: Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0.020) were significantly increased in aqueous humor samples from POAG versus cataract samples. For the majority of MMP/TIMP molar ratios calculated for the cataract group, TIMPs outweighed MMPs. In POAG, molar ratios of MMP2/TIMP1 (p = 0.007) and MMP9/TIMP1 (p = 0.005) showed a significant decrease, corresponding to an elevated excess of TIMPs over MMPs in POAG compared to cataract samples. Conversely, MMP2/TIMP3 (p = 0.045) and MMP3/TIMP3 (p = 0.032) molar ratios increased. Several MMP/TIMP molar ratios correlated with IOP (r = 0.476-0.609, p = 0.007-0.034) and PSD (r = -0.482 to -0.655, p = 0.005 0.046) in POAG samples and with age in cataract control samples. CONCLUSIONS: An imbalance among MMPs and TIMPs was found in glaucomatous aqueous humor samples, with a shift toward raised TIMP levels. This may result in the inhibition of MMP activity, leading to an altered ECM composition in the TM and thereby contributing to increased outflow resistance. PMID- 26539029 TI - Down-regulation of microRNA-155 attenuates retinal neovascularization via the PI3K/Akt pathway. AB - PURPOSE: We aimed to investigate the anti-angiogenic properties of miR-155 via in vitro and in vivo studies. METHODS: miR-155 was knocked down using lentivirus mediated RNA interference. The proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs) were measured using BrdU, Transwell, and Matrigel assays, respectively. An oxygen-induced retinopathy (OIR) model was induced using neonatal C57BL/6J pups. Anti-miR-155 was intravitreally injected on postnatal day 12, and the retinal non-perfused areas and extent of neovascularization were measured on postnatal day 18 using transcardiovascular fluorescein isothiocyanate (FITC)-dextran perfusion and retina sections. A laser induced choroidal neovascularization (CNV) model was induced in adult C57BL/6J mice. To evaluate the leakage areas, fundus fluorescein angiography was performed on day 14 after anti-miR-155 intravitreal injection. The neovascularization area of the CNV model was also examined in confocal and retina section studies. The expression levels of SHIP1 and p-Akt (Thr308, Ser473, and Thr450) were evaluated both in vitro and in vivo. RESULTS: The expression of miR-155 was elevated in HRMECs after treatment with vascular endothelial growth factor (VEGF) and in neovascularized mouse model retinas. Anti-miR-155 lentivirus reduced the VEGF induced proliferation, migration, and tube formation abilities of HRMECs. Anti miR-155 attenuated retinal neovascularization in in vivo CNV and OIR models. In VEGF-treated HRMECs and retina neovascularization models, p-Akt (Ser473) was significantly upregulated, while SHIP1 was downregulated. Conversely, the inhibition of miR-155 restored the expression of SHIP1 and reduced the phosphorylation of effectors in the Akt (Ser473) signaling pathway. CONCLUSIONS: The results revealed that the downregulation of miR-155 attenuated retinal neovascularization via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. PMID- 26539030 TI - Spectrum of germ-line RB1 gene mutations in Malaysian patients with retinoblastoma. AB - PURPOSE: The availability of molecular genetic testing for retinoblastoma (RB) in Malaysia has enabled patients with a heritable predisposition to the disease to be identified, which thus improves the clinical management of these patients and their families. In this paper, we presented our strategy for performing molecular genetic testing of the RB1 gene and the findings from our first 2 years of starting this service. METHODS: The peripheral blood of 19 RB probands, including seven bilateral and 12 unilateral cases, was obtained, and genomic DNA was extracted. Analysis of the RB1 exons and the promoter region was conducted first using PCR and direct sequencing. Next, multiplex ligation-dependent probe amplification (MLPA) analysis was performed for patients whom the first results were negative. For patients whom either the first or second method results were positive, parental samples were analyzed to determine the origin of the mutation. RESULTS: Ten RB1 mutations were identified in ten (52.6%) of the 19 probands (seven bilateral and three unilateral cases), of which 30.0% (3/10) was identified with MLPA. The detection rates in the bilateral and unilateral cases were 100.0% (7/7) and 25.0% (3/12), respectively. Three new RB1 mutations were discovered, two in patients with bilateral RB and one in patient with unilateral RB. Interestingly, all mutations detected with the PCR-sequencing method were predicted to create a premature stop codon. Eight mutations were proven to be de novo while one mutation was inherited from the mother in a family with a positive history of RB. CONCLUSIONS: Our results confirmed the heterogeneous nature of RB1 mutations and the predominantly de novo origin. The high prevalence of pathogenic truncating mutations was evident among local patients with RB. The combination of PCR sequencing and MLPA is recommended for sensitive identification of heritable RB cases. PMID- 26539031 TI - Effects of ranibizumab on TGF-beta1 and TGF-beta2 production by human Tenon's fibroblasts: An in vitro study. AB - PURPOSE: Inhibiting exaggerated wound healing responses, which are primarily mediated by human Tenon's fibroblast (HTF) migration and proliferation, has become the major determining factor for a successful trabeculectomy. Antivascular endothelial growth factor (anti-VEGF) has showed promising results as a potential antifibrotic candidate for use concurrently in trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. However, the effects on HTFs remain unclear. This study was conducted to understand the effects of ranibizumab on transforming growth factor (TGF)-beta1 and transforming growth factor (TGF)-beta2 expression by HTFs. METHODS: The effect of ranibizumab on HTF proliferation and cell viability was determined using 3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/ml were administered for 24, 48, and 72 h in serum and serum-free conditions. Supernatants and cell lysates from samples were assessed for TGF-beta1 and TGF beta2 mRNA and protein levels using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: At 48 h, 0.5 mg/ml of ranibizumab significantly induced cell death under serum-free culture conditions (p<0.05). Ranibizumab caused a significant reduction in TGF beta1 mRNA, but not for TGF-beta2. However, the total protein production of TGF beta1 and TGF-beta2 was unaffected by this anti-VEGF treatment. CONCLUSIONS: Exposure of HTFs to an intravitreal dose of ranibizumab significantly suppresses cell viability in vitro; however, the application seemed unable to affect the ultimate production of TGF-beta. Therefore, we highlighted ranibizumab as a potential antiscarring agent that acts via a different mechanism when used synergistically with another antifibrotic agent. Understanding the mechanism of actions of ranibizumab offers an additional view of a possible new rational therapeutic strategy. PMID- 26539033 TI - A Comprehensive Review of Tropical Milky White Mushroom (Calocybe indica P&C). AB - A compressive description of tropical milky white mushroom (Calocybe indica P&C var. APK2) is provided in this review. This mushroom variety was first identified in the eastern Indian state of West Bengal and can be cultivated on a wide variety of substrates, at a high temperature range (30~38C). However, no commercial cultivation was made until 1998. Krishnamoorthy 1997 rediscovered the fungus from Tamil Nadu, India and standardized the commercial production techniques for the first time in the world. This edible mushroom has a long shelf life (5~7 days) compared to other commercially available counterparts. A comprehensive and critical review on physiological and nutritional requirements viz., pH, temperature, carbon to nitrogen ratio, best carbon source, best nitrogen source, growth period, growth promoters for mycelia biomass production; substrate preparation; spawn inoculation; different supplementation and casing requirements to increase the yield of mushrooms has been outlined. Innovative and inexpensive methods developed to commercially cultivate milky white mushrooms on different lignocellulosic biomass is also described in this review. The composition profiles of milky white mushroom, its mineral contents and non enzymatic antioxidants are provided in comparison with button mushroom (Agaricus bisporus) and oyster mushroom (Pleurotus ostreatus). Antioxidant assay results using methanol extract of milky white mushroom has been provided along with the information about the compounds that are responsible for flavor profile both in fresh and dry mushrooms. Milky white mushroom extracts are known to have anti hyperglycemic effect and anti-lipid peroxidation effect. The advantage of growing at elevated temperature creates newer avenues to explore milky white mushroom cultivation economically around the world, especially, in humid tropical and sub tropical zones. Because of its incomparable productivity and shelf life to any other cultivated mushrooms in the world, milky white mushroom could play an important role in satisfying the growing market demands for edible mushrooms in the near future. PMID- 26539032 TI - The Zinc Transport Systems and Their Regulation in Pathogenic Fungi. AB - Zinc is an essential micronutrient required for many enzymes that play essential roles in a cell. It was estimated that approximately 3% of the total cellular proteins are required for zinc for their functions. Zinc has long been considered as one of the key players in host-pathogen interactions. The host sequesters intracellular zinc by utilizing multiple cellular zinc importers and exporters as a means of nutritional immunity. To overcome extreme zinc limitation within the host environment, pathogenic microbes have successfully evolved a number of mechanisms to secure sufficient concentrations of zinc for their survival and pathogenesis. In this review, we briefly discuss the zinc uptake systems and their regulation in the model fungus Saccharomyces cerevisiae and in major human pathogenic fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus gattii. PMID- 26539034 TI - Three New Monotypic Genera of the Caloplacoid Lichens (Teloschistaceae, Lichen Forming Ascomycetes). AB - Three monophyletic branches are strongly supported in a phylogenetic analysis of the Teloschistaceae based on combined data sets of internal transcribed spacer and large subunit nrDNA and 12S small subunit mtDNA sequences. These are described as new monotypic genera: Jasonhuria S. Y. Kondr., L. Lokos et S. -O. Oh, Loekoesia S. Y. Kondr., S. -O. Oh et J. -S. Hur and Olegblumia S. Y. Kondr., L. Lokos et J. -S. Hur. Three new combinations for the type species of these genera are proposed. PMID- 26539035 TI - Three New Records of Mortierella Species Isolated from Crop Field Soil in Korea. AB - Three new fungal species of the genus Mortierella, Mortierella zychae, Mortierella ambigua, and Mortierella indohii, have been reported in Korea. The fungi were encountered during a study on the fungal community of soil samples collected from different locations in Korea. The species were identified based on molecular and morphological analyses. This study presents detailed descriptions of the morphological observations and molecular phylogenetic analysis of these three fungi. All three species were found to be sensitive to triphenyltetrazolium chloride staining. M. zychae demonstrated the highest intensity of mycelial staining, indicating that this species has the highest potential to produce arachidonic acid of the three species. The staining results indicated that the newly recorded species could potentially be useful for arachidonic acid production. PMID- 26539036 TI - Phylogenetic Status of an Unrecorded Species of Curvularia, C. spicifera, Based on Current Classification System of Curvularia and Bipolaris Group Using Multi Loci. AB - A seed-borne fungus, Curvularia sp. EML-KWD01, was isolated from an indigenous wheat seed by standard blotter method. This fungus was characterized based on the morphological characteristics and molecular phylogenetic analysis. Phylogenetic status of the fungus was determined using sequences of three loci: rDNA internal transcribed spacer, large ribosomal subunit, and glyceraldehyde 3-phosphate dehydrogenase gene. Multi loci sequencing analysis revealed that this fungus was Curvularia spicifera within Curvularia group 2 of family Pleosporaceae. PMID- 26539037 TI - Aspergillus Associated with Meju, a Fermented Soybean Starting Material for Traditional Soy Sauce and Soybean Paste in Korea. AB - Aspergillus is an important fungal genus used for the fermentation of Asian foods; this genus is referred to as koji mold in Japan and China. A. oryzae, A. sojae, and A. tamari are used in the production of miso and shoyu in Japan, but a comprehensive taxonomic study of Aspergillus isolated from Meju, a fermented soybean starting material for traditional soy sauce and soybean paste in Korea, has not been conducted. In this study, various Aspergillus species were isolated during a study of the mycobiota of Meju, and the aspergilli were identified based on phenotypic characteristics and sequencing of the beta-tubulin gene. Most strains of Aspergillus were found to belong to the following sections: Aspergillus (n = 220), Flavi (n = 213), and Nigri (n = 54). The most commonly identified species were A. oryzae (n = 183), A. pseudoglaucus (Eurotium repens) (n = 81), A. chevalieri (E. chevalieri) (n = 62), A. montevidensis (E. amstelodami) (n = 34), A. niger (n = 21), A. tamari (n = 15), A. ruber (E. rubrum) (n = 15), A. proliferans (n = 14), and A. luchuensis (n = 14); 25 species were identified from 533 Aspergillus strains. Aspergillus strains were mainly found during the high temperature fermentation period in the later steps of Meju fermentation. PMID- 26539038 TI - Taxonomic Study of the Genus Abundisporus in Korea. AB - The polypore genus Abundisporus Ryvarden is characterized by resupinate to pileate fruitbodies with a purplish brown hymenophore, slightly thick-walled, pale yellowish and non-dextrinoid basidiospores, and causing white rot. A purple color hymenophore, an easily observable and striking character, was considered the main distinctive feature at the generic level within polypores. However, due to highly similar basidiocarp features, species identification within these purple polypores is particularly difficult. Three species of purple colored polypores have been reported in Korea (Abundisporus fuscopurpureus, A. pubertatis, and Fomitopsis rosea). Based on morphological re-examination, ecological information, and sequence analysis of the internal transcribed spacer, we showed that previous classification was incorrect and there is only one species (A. pubertatis) in Korea. We provide a detailed description of A. pubertatis in Korea, as well as a taxonomic key to distinguish wood rot fungi with a purple hymenophore. PMID- 26539039 TI - Diversity of Endophytic Fungi Associated with the Roots of Four Aquatic Plants Inhabiting Two Wetlands in Korea. AB - A total of 4 aquatic plants, Eleocharis kuroguwai Ohwi, Hydrocharis dubia Backer, Salvinia natans All., and Zizania latifolia Turcz., were sampled from representative two wetlands of South Korea. A total of 38 endophytic fungal strains were isolated from aquatic plants native to the Daepyeong wetland, and 27 strains were isolated from the Jilnal wetland. The internal transcribed spacer regions of fungal isolates were sequenced and a phylogenetic analysis was performed. In addition, endophytic fungal diversity from each wetland and host plant species was deduced. A total of 25 fungal genera were purely isolated, and 16 fungal genera were isolated from each of the two wetlands. Commonly isolated genera from both wetlands were Aspergillus, Cladosporium, Clonostachys, Fusarium, Leptosphaeria, Penicillium, and Talaromyces. This study revealed that fungal diversity varied with environmental conditions and by host plant in representative two wetlands. PMID- 26539040 TI - Mushroom Flora of Ulleung-gun and a Newly Recorded Bovista Species in the Republic of Korea. AB - We conducted five times surveys, in June, September and October in 2012; June and September 2013, to catalog the mushroom flora in Ulleung-gun, Republic of Korea. More than 400 specimens were collected, and 317 of the specimens were successfully sequenced using the ribosomal DNA internal transcribed spacer barcode marker. We also surveyed the morphological characteristics of the sequenced specimens. The specimens were classified into 2 phyla, 7 classes, 21 orders, 59 families, 122 genera, and 221 species, and were deposited in the herbarium of Korea National Arboretum. Among the collected species, 72% were saprophytic, 25% were symbiotic, and 3% were parasitic. The most common order was Agaricales (189 specimens, 132 species), followed by Polyporales (47 specimens, 27 species), Russulales (31 specimens, 22 species), Boletales (10 specimens, 7 species), and so on. Herein, we also reported the first Bovista species in Korea, which was collected from Dokdo, the far-eastern island of Korea. PMID- 26539041 TI - The Mycobiota of Air Inside and Outside the Meju Fermentation Room and the Origin of Meju Fungi. AB - The fungi on Meju are known to play an important role as degrader of macromolecule of soybeans. In order to elucidate the origin of fungi on traditional Meju, mycobiota of the air both inside and outside traditional Meju fermentation rooms was examined. From 11 samples of air collected from inside and outside of 7 Meju fermentation rooms, 37 genera and 90 species of fungi were identified. In outside air of the fermentation room, Cladosporium sp. and Cladosporium cladosporioides were the dominant species, followed by Cladosporium tenuissimum, Eurotium sp., Phoma sp., Sistotrema brinkmannii, Alternaria sp., Aspergillus fumigatus, Schizophyllum commune, and Penicillium glabrum. In inside air of the fermentation room, Cladosporium sp., Aspergillus oryzae, Penicillium chrysogenum, Asp. nidulans, Aspergillus sp., Cla. cladosporioides, Eurotium sp., Penicillium sp., Cla. tenuissimum, Asp. niger, Eur. herbariorum, Asp. sydowii, and Eur. repens were collected with high frequency. The concentrations of the genera Aspergillus, Eurotium, and Penicillium were significantly higher in inside air than outside air. From this result and those of previous reports, the origin of fungi present on Meju was inferred. Of the dominant fungal species present on Meju, Lichtheimia ramosa, Mucor circinelloides, Mucor racemosus, and Scopulariopsis brevicaulis are thought to be originated from outside air, because these species are not or are rarely isolated from rice straw and soybean; however, they were detected outside air of fermentation room and are species commonly found in indoor environments. However, Asp. oryzae, Pen. polonicum, Eur. repens, Pen. solitum, and Eur. chevalieri, which are frequently found on Meju, are common in rice straw and could be transferred from rice straw to Meju. The fungi grow and produce abundant spores during Meju fermentation, and after the spores accumulate in the air of fermentation room, they could influence mycobiota of Meju fermentation in the following year. This could explain why concentrations of the genera Aspergillus, Eurotium, and Penicillium are much higher inside than outside of the fermentation rooms. PMID- 26539042 TI - Isolation and Identification of Yeasts from Wild Flowers Collected around Jangseong Lake in Jeollanam-do, Republic of Korea, and Characterization of the Unrecorded Yeast Bullera coprosmaensis. AB - Several types of yeasts were isolated from wild flowers around Jangseong Lake in Jeollanam-do, Republic of Korea and identified by comparing the nucleotide sequences of the PCR amplicons for the D1/D2 variable domain of the 26S ribosomal DNA using Basic Local Alignment Search Tool (BLAST) analysis. In total, 60 strains from 18 species were isolated, and Pseudozyma spp. (27 strains), which included Pseudozyma rugulosa (7 strains) and Pseudozyma aphidis (6 strains), was dominant species. Among the 60 strains, Bullera coprosmaensis JS00600 represented a newly recorded yeast strain in Korea, and its microbiological characteristics were investigated. The yeast cell has an oval-shaped morphology measuring 1.4 * 1.7 um in size. Bullera coprosmaensis JS00600 is an asporous yeast that exhibits no pseudomycelium formation. It grew well in vitamin-free medium as well as in yeast extract-malt extract broth and yeast extract-peptone-dextrose (YPD) broth, and it is halotolerant growing in 10% NaCl-containing YPD broth. PMID- 26539043 TI - Screening Molecular Chaperones Similar to Small Heat Shock Proteins in Schizosaccharomyces pombe. AB - To screen molecular chaperones similar to small heat shock proteins (sHsps), but without alpha-crystalline domain, heat-stable proteins from Schizosaccharomyces pombe were analyzed by 2-dimensional electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Sixteen proteins were identified, and four recombinant proteins, including cofilin, NTF2, pyridoxin biosynthesis protein (Snz1) and Wos2 that has an alpha-crystalline domain, were purified. Among these proteins, only Snz1 showed the anti-aggregation activity against thermal denaturation of citrate synthase. However, pre-heating of NTF2 and Wos2 at 70C for 30 min, efficiently prevented thermal aggregation of citrate synthase. These results indicate that Snz1 and NTF2 possess molecular chaperone activity similar to sHsps, even though there is no alpha-crystalline domain in their sequences. PMID- 26539044 TI - Differential Expression of Laccase Genes in Pleurotus ostreatus and Biochemical Characterization of Laccase Isozymes Produced in Pichia pastoris. AB - In this study, transcriptome analysis of twelve laccase genes in Pleurotus ostreatus revealed that their expression was differentially regulated at different developmental stages. Lacc5 and Lacc12 were specifically expressed in fruiting bodies and primordia, respectively, whereas Lacc6 was expressed at all developmental stages. Lacc1 and Lacc3 were specific to the mycelial stage in solid medium. In order to investigate their biochemical characteristics, these laccases were heterologously expressed in Pichia pastoris using the pPICHOLI-2 expression vector. Expression of the laccases was facilitated by intermittent addition of methanol as an inducer and sole carbon source, in order to reduce the toxic effects associated with high methanol concentration. The highest expression was observed when the recombinant yeast cells were grown for 5 days at 15C with intermittent addition of 1% methanol at a 12-hr interval. Investigation of enzyme kinetics using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as a substrate revealed that the primordium-specific laccase Lacc12 was 5.4-fold less active than Lacc6 at low substrate concentration with respect to ABTS oxidation activity. The optimal pH and temperature of Lacc12 were 0.5 pH units and 5C higher than those of Lacc6. Lacc12 showed maximal activity at pH 3.5 and 50C, which may reflect the physiological conditions at the primordiation stage. PMID- 26539045 TI - Efficacy of Chaetomium Species as Biological Control Agents against Phytophthora nicotianae Root Rot in Citrus. AB - Thailand is one of the largest citrus producers in Southeast Asia. Pathogenic infection by Phytophthora, however, has become one of major impediments to production. This study identified a pathogenic oomycete isolated from rotted roots of pomelo (Citrus maxima) in Thailand as Phytophthora nicotianae by the internal transcribed spacer ribosomal DNA sequence analysis. Then, we examined the in vitro and in vivo effects of Chaetomium globosum, Chaetomium lucknowense, Chaetomium cupreum and their crude extracts as biological control agents in controlling this P. nicotianae strain. Represent as antagonists in biculture test, the tested Chaetomium species inhibited mycelial growth by 50~56% and parasitized the hyphae, resulting in degradation of P. nicotianae mycelia after 30 days. The crude extracts of these Chaetomium species exhibited antifungal activities against mycelial growth of P. nicotianae, with effective doses of 2.6~101.4 ug/mL. Under greenhouse conditions, application of spores and methanol extracts of these Chaetomium species to pomelo seedlings inoculated with P. nicotianae reduced root rot by 66~71% and increased plant weight by 72~85% compared to that in the control. The method of application of antagonistic spores to control the disease was simple and economical, and it may thus be applicable for large-scale, highly effective biological control of this pathogen. PMID- 26539046 TI - Biotransformation of (-)-alpha-Pinene by Whole Cells of White Rot Fungi, Ceriporia sp. ZLY-2010 and Stereum hirsutum. AB - Two white rot fungi, Ceriporia sp. ZLY-2010 (CER) and Stereum hirsutum (STH) were used as biocatalysts for the biotransformation of (-)-alpha-pinene. After 96 hr, CER converted the bicyclic monoterpene hydrocarbon (-)-alpha-pinene into alpha terpineol (yield, 0.05 g/L), a monocyclic monoterpene alcohol, in addition to, other minor products. Using STH, verbenone was identified as the major biotransformed product, and minor products were myrtenol, camphor, and isopinocarveol. We did not observe any inhibitory effects of substrate or transformed products on mycelial growth of the fungi. The activities of fungal manganese-dependent peroxidase and laccase were monitored for 15 days to determine the enzymatic pathways related to the biotransformation of (-)-alpha pinene. We concluded that a complex of enzymes, including intra- and extracellular enzymes, were involved in terpenoid biotransformation by white rot fungi. PMID- 26539047 TI - Bioprospecting Endophytic Fungi and Their Metabolites from Medicinal Tree Aegle marmelos in Western Ghats, India. AB - The increasing emergence of lead drugs for the resistance produced by the pathogenic strains and arrival of new diseases have initiated the need for searching novel metabolites with best anticancer and antimicrobial properties than the existing one. With this view, the investigation was conducted for the isolation, identification, and biological evaluation of potential endophytic fungi of Aegle marmelos, a medicinal tree used for more than three decades, for curing various disorders. A total of 169 endophytic fungal strains obtained from sampling and among those 67 were pigmented strains. Upon antagonistic screening, five endophytic fungal strains exhibited antagonistic potentiality by inhibiting the pathogens. These five potent strains were characterized at molecular level by sequencing the amplified internal transcribed spacer (ITS) 1 and ITS 4 regions of rDNA and they were grouped under order Pleosporales, Eurotiales, and Capnodiales. The metabolites from the respective strains were produced in fungal culturing media and extracted using polar solvents. Further, the extracts of five endophytes manifested antimicrobial activity against tested clinical pathogens and Alternaria alternata (FC39BY), Al. citrimacularis (FC8ABr), and Curvularia australiensis (FC2AP) exhibited significant antimicrobial profile against 9 of 12 tested pathogens, showing broad spectrum activity. The antioxidant levels of all the five endophytes revealed the highest activity at least concentrations, and major activity was unveiled by the members of order Pleosporales FC2AP and FC8ABr. This research explains the value of endophytic fungal extracts and its significance of antimicrobial and antioxidant properties. PMID- 26539048 TI - Water Extract from Spent Mushroom Substrate of Hericium erinaceus Suppresses Bacterial Wilt Disease of Tomato. AB - Culture filtrates of six different edible mushroom species were screened for antimicrobial activity against tomato wilt bacteria Ralstonia solanacearum B3. Hericium erinaceus, Lentinula edodes (Sanjo 701), Grifola frondosa, and Hypsizygus marmoreus showed antibacterial activity against the bacteria. Water, n butanol, and ethyl acetate extracts of spent mushroom substrate (SMS) of H. erinaceus exhibited high antibacterial activity against different phytopathogenic bacteria: Pectobacterium carotovorum subsp. carotovorum, Agrobacterium tumefaciens, R. solanacearum, Xanthomonas oryzae pv. oryzae, X. campestris pv. campestris, X. axonopodis pv. vesicatoria, X. axonopodis pv. citiri, and X. axonopodis pv. glycine. Quantitative real-time PCR revealed that water extracts of SMS (WESMS) of H. erinaceus induced expressions of plant defense genes encoding beta-1,3-glucanase (GluA) and pathogenesis-related protein-1a (PR-1a), associated with systemic acquired resistance. Furthermore, WESMS also suppressed tomato wilt disease caused by R. solanacearum by 85% in seedlings and promoted growth (height, leaf number, and fresh weight of the root and shoot) of tomato plants. These findings suggest the WESMS of H. erinaceus has the potential to suppress bacterial wilt disease of tomato through multiple effects including antibacterial activity, plant growth promotion, and defense gene induction. PMID- 26539049 TI - Methyl 9-Oxo-(10E,12E)-octadecadienoate Isolated from Fomes fomentarius Attenuates Lipopolysaccharide-Induced Inflammatory Response by Blocking Phosphorylation of STAT3 in Murine Macrophages. AB - Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin E2 through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor kappaB, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo. PMID- 26539050 TI - Cloning and Expression Analysis of Phenylalanine Ammonia-Lyase Gene in the Mycelium and Fruit Body of the Edible Mushroom Flammulina velutipes. AB - Phenylalanine ammonia-lyase (PAL) gene is known to be expressed in plants, and is involved in the differentiation, growth and synthesis of secondary metabolites. However, its expression in fungi remains to be explored. To understand its expression in mushroom fungi, the PAL gene of the edible mushroom Flammulina velutipes (Fvpal) was cloned and characterized. The cloned Fvpal consists of 2,175 bp, coding for a polypeptide containing 724 amino acids and having 11 introns. The translated amino acid sequence of Fvpal shares a high identity (66%) with that of ectomycorrhizal fungus Tricholoma matsutake. Distinctively, the Fvpal expression in the mycelium was higher in minimal medium supplemented with L tyrosine than with other aromatic amino acids. During cultivation of the mushroom on sawdust medium, Fvpal expression in the fruit body correspondingly increased as the mushroom grew. In the fruiting body, Fvpal was expressed more in the stipe than in the pileus. These results suggest that F. velutipes PAL activity differs in the different organs of the mushroom. Overall, this is first report to show that the PAL gene expression is associated with mushroom growth in fungi. PMID- 26539051 TI - Antifungal Substances from Streptomyces sp. A3265 Antagonistic to Plant Pathogenic Fungi. AB - In a previous study, we identified a Streptomyces sp., A3265, as exhibiting potent antifungal activity against various plant pathogenic fungi, including Botrytis cinerea, Colletotrichum gloeosporioides, and Rhizoctonia solani. This strain also exhibited a biocontrolling effect against ginseng root rot and damping-off disease, common diseases of ginseng and other crops. In this study, we isolated two antifungal substances responsible for this biocontrolling effect via Diaion HP-20 and Sephadex LH-20 column chromatography, medium pressure liquid chromatography, and high-performance liquid chromatography. These compounds were identified as guanidylfungin A and methyl guanidylfungin A by spectroscopic methods. These compounds exhibited potent antimicrobial activity against various plant pathogenic fungi as well as against bacteria. PMID- 26539052 TI - Antagonistic Effect of Streptomyces sp. BS062 against Botrytis Diseases. AB - The use of microorganisms and their secreted molecules to prevent plant diseases is considered an attractive alternative and way to supplement synthetic fungicides for the management of plant diseases. Strain BS062 was selected based on its ability to inhibit the mycelial growth of Botrytis cinerea, a major causal fungus of postharvest root rot of ginseng and strawberry gray mold disease. Strain BS062 was found to be closely related to Streptomyces hygroscopicus (99% similarity) on the basis of 16S ribosomal DNA sequence analysis. Postharvest root rot of ginseng and strawberry gray mold disease caused by B. cinerea were controlled up to 73.9% and 58%, respectively, upon treatment with culture broth of Streptomyces sp. BS062. These results suggest that strain BS062 may be a potential agent for controlling ginseng postharvest root rot and strawberry gray mold disease. PMID- 26539053 TI - First Report of Fusarium subglutinans Causing Leaf Spot Disease on Cymbidium Orchids in Korea. AB - In 2006~2010, leaf spot symptoms, that is, small, yellow spots that turned into dark brown-to-black lesions surrounded by a yellow halo, were observed on Cymbidium spp. in Gongju, Taean, and Gapyeong in Korea. A Fusarium species was continuously isolated from symptomatic leaves; in pathogenicity testing, isolates caused leaf spot symptoms consisting of sunken, dark brown lesions similar to the original ones. The causal pathogen was identified as Fusarium subglutinans based on morphological and translation elongation factor 1-alpha sequence analyses. This is the first report of F. subglutinans as the cause of leaf spot disease in Cymbidium spp. in Korea. PMID- 26539054 TI - Sooty Mould Disease Caused by Leptoxyphium kurandae on Kenaf. AB - In September 2013, we discovered sooty mould growing on kenaf with the extrafloral nectaries in Iksan, Korea and identified the causative fungus as Leptoxyphium kurandae based on morphological characteristics and phylogenetic analyses. This is the first report of sooty mould caused by L. kurandae on kenaf in Korea and globally. PMID- 26539055 TI - First Report of Leaf Rust Caused by Puccinia caricis in Farfugium japonicum in Korea. AB - Farfugium japonicum is used in traditional medicine and as an edible herb in China and Korea. In July 2013, leaf spots were observed in F. japonicum seedlings at Ulleung Island, Gyeongsangbuk Province, Korea. Early symptoms on the leaf adaxial surface included roughly circular yellow spots that later developed brown, necrotic centers. The aecia were hypophyllous, cupulate, yellowish, 180~430 um in diameter, clustered, and erumpent with a peridium with a recurved margin. The aeciospores were globoid, 14~17 * 13~16 um, light yellow or colorless, and densely verrucose. The 28S rDNA sequence of the isolate was identical to each other and shared 99% identity with Puccinia caricis. This is the first report of rust caused by P. caricis in F. japonicum in Korea or elsewhere in the world. PMID- 26539056 TI - Cladosporium cladosporioides and C. tenuissimum Cause Blossom Blight in Strawberry in Korea. AB - Blossom blight in strawberry was first observed in a green house in Nonsan, Damyang, and Geochang areas of Korea, between early January to April of 2012. Disease symptoms started as a grey fungus formed on the stigma, which led to the blossom blight and eventually to black rot and necrosis of the entire flower. We isolated the fungi purely from the infected pistils and maintained them on potato dextrose agar (PDA) slants. To test Koch's postulates, we inoculated the fungi and found that all of the isolates caused disease symptoms in the flower of strawberry cultivars (Seolhyang, Maehyang, and Kumhyang). The isolates on PDA had a velvet-like appearance, and their color ranged between olivaceous-brown and smoky-grey to olive and almost black. The intercalary conidia of the isolates were elliptical to limoniform, with sizes ranging from 5.0~10.5 * 2.5~3.0 um to 4.0~7.5 * 2.0~3.0 um, respectively. The secondary ramoconidia of these isolates were 0- or 1-septate, with sizes ranging betweem 10.0~15.0 * 2.5~3.7 um and 8.7~11.2 * 2.5~3.2 um, respectively. A combined sequence analysis of the internal transcribed spacer regions, partial actin (ACT), and translation elongation factor 1-alpha (TEF) genes revealed that the strawberry isolates belonged to two groups of authentic strains, Cladosporium cladosporioides and C. tenuissimum. Based on these results, we identified the pathogens causing blossom blight in strawberries in Korea as being C. cladosporioides and C. tenuissimum. PMID- 26539057 TI - Genotypes of Clinical and Environmental Isolates of Cryptococcus neoformans and Cryptococcus gattii in Korea. AB - Multilocus sequence typing analysis was applied to determine the genotypes of 147 (137 clinical and 10 environmental) Cryptococcus neoformans and three clinical Cryptococcus gattii isolates from 1993 to 2014 in Korea. Among the 137 clinical isolates of C. neoformans, the most prevalent genotype was ST5 (n = 131), followed by ST31 (n = 5) and ST127 (n = 1). Three C. gattii strains were identified as ST57, ST7, and ST113. All environmental isolates were identified as C. neoformans with two genotypes, ST5 (n = 7) and ST31 (n = 3). Our results show that C. neoformans isolates in Korea are genetically homogeneous, and represent a close genetic relationship between clinical and environmental isolates. PMID- 26539058 TI - First Report and Characterization of Pestalotiopsis ellipsospora Causing Canker on Acanthopanax divaricatus. AB - Acanthopanax divaricatus, a member of the Araliaceae family, has been used as an invigorant in traditional Korean medicine. During disease monitoring, a stem with small, irregular, brown lesions was sampled at a farm in Cheonan in 2011. The symptoms seen were sunken cankers and reddish-brown needles on the infected twig. The isolated fungal colonies were whitish, having crenated edges and aerial mycelium on the surface, and with black gregarious fruiting bodies. The reverse plate was creamy white. Conidia were 17~22 * 3.5~4.2 um, fusiform, 4-septate, and straight to slightly curved. The nucleotide sequence of the partial translation elongation factor 1 alpha gene of the fungal isolate, shares 99% sequence identity with that of known Pestalotiopsis ellipsospora. Based on the results of the morphological and molecular analyses, the fungal isolate was identified as P. ellipsospora. In Korea, this is the first report of canker on A. divaricatus. PMID- 26539059 TI - Erratum: Alternaria in Food: Ecophysiology, Mycotoxin Production and Toxicology. AB - [This corrects the article on p. 93 in vol. 43, PMID: 26190916.]. PMID- 26539060 TI - Improving the installation of renewable heating technology in UK social housing properties through user centred design. AB - Social housing organisations are increasingly installing renewable energy technologies, particularly for the provision of heating and hot water. To meet carbon reduction targets, uptake and installation must allow occupants to use the technology effectively. This paper describes research which investigated the service of installing heat pumps into UK social housing properties, from both landlords' and tenants' experiences. Adopting a user centred design approach, the research was in three phases: an exploration study to investigate landlords' and tenants' experiences of heat pump installation and use; refinement and development of the requirements for improved service delivery, primarily technology introduction and control; and the development and initial evaluation of an information leaflet as a key touchpoint in the service delivery. Recommendations for improved service delivery, to enable heat pumps to be accepted and used more effectively, are presented, as well as reflection on the process of applying user centred design in this context. In a relatively immature area of industry, installations to date have been heavily focused on technical aspects. This paper provides an insight into the human aspects of the service delivery of heat pumps in social housing, providing designers and social housing landlords with insight about how to improve the service. PMID- 26539063 TI - Detection of genetic variation using dual-labeled peptide nucleic acid (PNA) probe-based melting point analysis. AB - BACKGROUND: Thermal denaturation of probe-target hybrid is highly reproducible, and which makes probe melting point analysis reliable in the detection of mutations, polymorphisms and epigenetic differences in DNA. To improve resolution of these detections, we used dual-labeled (quencher and fluorescence), full base of peptide nucleic acid (PNA) probe for fluorescence probe based melting point analysis. Because of their uncharged nature and peptide bond-linked backbone, PNA probes have more favorable hybridization properties, which make a large difference in the melting temperature between specific hybridization and partial hybridization. RESULTS: Here, we have shown that full base dual-labeled PNA is apt material for fluorescence probe-based melting point analysis with large difference in the melting temperature between full specific hybridization and that of partial hybridization, including insertion and deletion. In case of narrowly distributed mutations, PNA probe effectively detects three mutations in a single reaction tube with three probes. Moreover, we successfully diagnose virus analogues with amplification and melting temperature signal. Lastly, Melting temperature of PNA oligomer can be easily adjusted just by adding gamma modified PNA probe. CONCLUSIONS: The PNA probes offer advantage of improved flexibility in probe design, which could be used in various applications in mutation detection among a wide range of spectrums. PMID- 26539062 TI - A Novel Highly Thermostable Multifunctional Beta-Glycosidase from Crenarchaeon Acidilobus saccharovorans. AB - We expressed a putative beta-galactosidase Asac_1390 from hyperthermophilic crenarchaeon Acidilobus saccharovorans in Escherichia coli and purified the recombinant enzyme. Asac_1390 is composed of 490 amino acid residues and showed high sequence similarity to family 1 glycoside hydrolases from various thermophilic Crenarchaeota. The maximum activity was observed at pH 6.0 and 93 degrees C. The half-life of the enzyme at 90 degrees C was about 7 hours. Asac_1390 displayed high tolerance to glucose and exhibits hydrolytic activity towards cellobiose and various aryl glucosides. The hydrolytic activity with p nitrophenyl (pNP) substrates followed the order pNP-beta-D-galactopyranoside (328 U mg(-1)), pNP-beta-D-glucopyranoside (246 U mg(-1)), pNP-beta-D-xylopyranoside (72 U mg(-1)), and pNP-beta-D-mannopyranoside (28 U mg(-1)). Thus the enzyme was actually a multifunctional beta-glycosidase. Therefore, the utilization of Asac_1390 may contribute to facilitating the efficient degradation of lignocellulosic biomass and help enhance bioconversion processes. PMID- 26539064 TI - Generating a human neonatal brain atlas for superior normalization accuracy. PMID- 26539061 TI - Archaeal MCM Proteins as an Analog for the Eukaryotic Mcm2-7 Helicase to Reveal Essential Features of Structure and Function. AB - In eukaryotes, the replicative helicase is the large multisubunit CMG complex consisting of the Mcm2-7 hexameric ring, Cdc45, and the tetrameric GINS complex. The Mcm2-7 ring assembles from six different, related proteins and forms the core of this complex. In archaea, a homologous MCM hexameric ring functions as the replicative helicase at the replication fork. Archaeal MCM proteins form thermostable homohexamers, facilitating their use as models of the eukaryotic Mcm2-7 helicase. Here we review archaeal MCM helicase structure and function and how the archaeal findings relate to the eukaryotic Mcm2-7 ring. PMID- 26539065 TI - Model-Based Bayesian Reinforcement Learning in Large Structured Domains. AB - Model-based Bayesian reinforcement learning has generated significant interest in the AI community as it provides an elegant solution to the optimal exploration exploitation tradeoff in classical reinforcement learning. Unfortunately, the applicability of this type of approach has been limited to small domains due to the high complexity of reasoning about the joint posterior over model parameters. In this paper, we consider the use of factored representations combined with online planning techniques, to improve scalability of these methods. The main contribution of this paper is a Bayesian framework for learning the structure and parameters of a dynamical system, while also simultaneously planning a (near )optimal sequence of actions. PMID- 26539066 TI - Safe for Generations to Come. PMID- 26539067 TI - Aging, Spirituality, and Time: A Qualitative Study. AB - We examined the concepts of aging, time, spirituality, and future care needs in four randomly selected informants from a group of 54 never-married childless older women. Using data from the Generativity and Lifestyles of Older Women (GLOW) study, we questioned how women's perceptions of these concepts came together in current older age. We employed cultural theory, (our theoretical framework), ethnography, (our methodological framework), and phenomenology, (our philosophical foundation) to produce a portrait of each woman interviewed. Through a three-session interview process, we elicited the women's life stories, reasons for childlessness, and topics that emerged as significant to the women, including aging, a sense of time remaining, and spirituality. A key finding was that the context of each woman's life, both biographical and historical, transpired as a foundation for these concepts. That is, a woman's "place in time" shaped their experiences of aging, as well as her reasons for childlessness and perceptions of finitude. PMID- 26539068 TI - Prevalence and association of smokeless tobacco use with the development of periodontal pocket among adult males in Dawan Valley, Yemen: a cross-sectional study. AB - BACKGROUND: The traditional type of smokeless tobacco used in the Arabian Peninsula, particularly common in Yemen, is called shammah. This study aims to determine the prevalence of shammah use and its association with the development of periodontal pockets. Other associated factors with the development of periodontal pocket were also determined. METHODS: This cross-sectional study included 346 adult males aged 18 years old to 68 years old. Socio-demographic characteristics, oral hygiene practices, and shammah use history were surveyed by using a structured interview questionnaire. The clinical assessment for the presence or absence of periodontal pockets was assessed on the basis of community periodontal index. The chi-square test was used to assess significant differences in study groups in terms of the presence of periodontal pockets. Multivariable logistic regression was selected to assess potential associated factors with the development of periodontal pockets. RESULTS: Among the 346 adult males, 248 (71.7 %), 30 (8.6 %), and 68 (19.7 %) males never used shammah, were former shammah users, and were current shammah users, respectively. The significant associated factors with the development of periodontal pocket were age group (30 years old and above) (Adjusted Odds Ratio (AOR) = 2.03, 95 % CI: 1.13, 3.65; P = 0.018), low family income category (AOR = 2.35, 95 % CI: 1.39, 3.99; P = 0.001), former shammah user (AOR = 2.66, 95 %: CI: 1.15, 6.15; P = 0.022), and current shammah user (AOR = 6.62, 95 %: CI: 3.59, 12.21; P = 0.001). CONCLUSIONS: The results revealed that periodontal pockets were significantly associated with age group (30 years old and above), low family income category, former shammah use, and current shammah use. The findings of the current study highlighted the need to develop comprehensive shammah prevention programs and reduce periodontal disease and other shammah-associated diseases. PMID- 26539069 TI - Twitter users' reaction to a chain pharmacy's decision to end tobacco sales. AB - BACKGROUND: Reducing the number of tobacco outlets may help reduce smoking uptake and use; public support for such action is essential. We explored how Twitter users responded to the announcement by US pharmacy chain CVS that it was voluntarily ending tobacco sales. METHODS: We used Twitter's application programming interface to retrieve tweets and retweets posted over an 8-day period in February 2014 that contained two trending CVS-related hashtags (#cvs and #cvsquits). We manually coded 6,257 tweets as positive, negative, or neutral. RESULTS: The majority of tweets were positive (56.0 %) or neutral (39.4 %). CONCLUSIONS: There was little disapproval of CVS's decision to end tobacco sales among Twitter users, possibly due to the voluntary nature of the decision. The level of support suggests that CVS's image and bottom line will not suffer as a result. Further voluntary actions to end tobacco sales - which may lay the groundwork for legislation -- should be incentivized and supported. PMID- 26539071 TI - Statistical image analysis of longitudinal RAVENS images. AB - Regional analysis of volumes examined in normalized space (RAVENS) are transformation images used in the study of brain morphometry. In this paper, RAVENS images are analyzed using a longitudinal variant of voxel-based morphometry (VBM) and longitudinal functional principal component analysis (LFPCA) for high-dimensional images. We demonstrate that the latter overcomes the limitations of standard longitudinal VBM analyses, which does not separate registration errors from other longitudinal changes and baseline patterns. This is especially important in contexts where longitudinal changes are only a small fraction of the overall observed variability, which is typical in normal aging and many chronic diseases. Our simulation study shows that LFPCA effectively separates registration error from baseline and longitudinal signals of interest by decomposing RAVENS images measured at multiple visits into three components: a subject-specific imaging random intercept that quantifies the cross-sectional variability, a subject-specific imaging slope that quantifies the irreversible changes over multiple visits, and a subject-visit specific imaging deviation. We describe strategies to identify baseline/longitudinal variation and registration errors combined with covariates of interest. Our analysis suggests that specific regional brain atrophy and ventricular enlargement are associated with multiple sclerosis (MS) disease progression. PMID- 26539070 TI - A novel biomarker of amnestic MCI based on dynamic cross-frequency coupling patterns during cognitive brain responses. AB - The detection of mild cognitive impairment (MCI), the transitional stage between normal cognitive changes of aging and the cognitive decline caused by AD, is of paramount clinical importance, since MCI patients are at increased risk of progressing into AD. Electroencephalographic (EEG) alterations in the spectral content of brainwaves and connectivity at resting state have been associated with early-stage AD. Recently, cognitive event-related potentials (ERPs) have entered into the picture as an easy to perform screening test. Motivated by the recent findings about the role of cross-frequency coupling (CFC) in cognition, we introduce a relevant methodological approach for detecting MCI based on cognitive responses from a standard auditory oddball paradigm. By using the single trial signals recorded at Pz sensor and comparing the responses to target and non target stimuli, we first demonstrate that increased CFC is associated with the cognitive task. Then, considering the dynamic character of CFC, we identify instances during which the coupling between particular pairs of brainwave frequencies carries sufficient information for discriminating between normal subjects and patients with MCI. In this way, we form a multiparametric signature of impaired cognition. The new composite biomarker was tested using data from a cohort that consists of 25 amnestic MCI patients and 15 age-matched controls. Standard machine-learning algorithms were employed so as to implement the binary classification task. Based on leave-one-out cross-validation, the measured classification rate was found reaching very high levels (95%). Our approach compares favorably with the traditional alternative of using the morphology of averaged ERP response to make the diagnosis and the usage of features from spectro-temporal analysis of single-trial responses. This further indicates that task-related CFC measurements can provide invaluable analytics in AD diagnosis and prognosis. PMID- 26539072 TI - A physical action potential generator: design, implementation and evaluation. AB - The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (O = 20 MUm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 +/- 0.01 MUV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 +/- 0.05 mV (gain of 40x) at time 196.4 +/- 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID- 26539073 TI - The role of inflammation in schizophrenia. AB - High levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA) system and other immune functions. Another line of evidence demonstrates that chronic (dis)stress is associated with immune activation. The vulnerability stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis of schizophrenia, because stress may increase pro-inflammatory cytokines and even contribute to a lasting pro-inflammatory state. Immune alterations influence the dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission. The activated immune system in turn activates the enzyme indoleamine 2,3 dioxygenase (IDO) of the tryptophan/kynurenine metabolism which influences the serotonergic and glutamatergic neurotransmission via neuroactive metabolites such as kynurenic acid. The described loss of central nervous system volume and the activation of microglia, both of which have been clearly demonstrated in neuroimaging studies of schizophrenia patients, match the assumption of a (low level) inflammatory neurotoxic process. Further support for the inflammatory hypothesis comes from the therapeutic benefit of anti-inflammatory medication. Metaanalyses have shown an advantageous effect of cyclo-oxygenase-2 inhibitors in early stages of schizophrenia. Moreover, intrinsic anti-inflammatory, and immunomodulatory effects of antipsychotic drugs are known since a long time. Anti inflammatory effects of antipsychotics, therapeutic effects of anti-inflammtory compounds, genetic, biochemical, and immunological findings point to a major role of inflammation in schizophrenia. PMID- 26539074 TI - A memristive spiking neuron with firing rate coding. AB - Perception, decisions, and sensations are all encoded into trains of action potentials in the brain. The relation between stimulus strength and all-or nothing spiking of neurons is widely believed to be the basis of this coding. This initiated the development of spiking neuron models; one of today's most powerful conceptual tool for the analysis and emulation of neural dynamics. The success of electronic circuit models and their physical realization within silicon field-effect transistor circuits lead to elegant technical approaches. Recently, the spectrum of electronic devices for neural computing has been extended by memristive devices, mainly used to emulate static synaptic functionality. Their capabilities for emulations of neural activity were recently demonstrated using a memristive neuristor circuit, while a memristive neuron circuit has so far been elusive. Here, a spiking neuron model is experimentally realized in a compact circuit comprising memristive and memcapacitive devices based on the strongly correlated electron material vanadium dioxide (VO2) and on the chemical electromigration cell Ag/TiO2-x /Al. The circuit can emulate dynamical spiking patterns in response to an external stimulus including adaptation, which is at the heart of firing rate coding as first observed by E.D. Adrian in 1926. PMID- 26539076 TI - Benchmarking neuromorphic systems with Nengo. AB - Nengo is a software package for designing and simulating large-scale neural models. Nengo is architected such that the same Nengo model can be simulated on any of several Nengo backends with few to no modifications. Backends translate a model to specific platforms, which include GPUs and neuromorphic hardware. Nengo also contains a large test suite that can be run with any backend and focuses primarily on functional performance. We propose that Nengo's large test suite can be used to benchmark neuromorphic hardware's functional performance and simulation speed in an efficient, unbiased, and future-proof manner. We implement four benchmark models and show that Nengo can collect metrics across five different backends that identify situations in which some backends perform more accurately or quickly. PMID- 26539075 TI - A comparison of FreeSurfer-generated data with and without manual intervention. AB - This paper examined whether FreeSurfer-generated data differed between a fully automated, unedited pipeline and an edited pipeline that included the application of control points to correct errors in white matter segmentation. In a sample of 30 individuals, we compared the summary statistics of surface area, white matter volumes, and cortical thickness derived from edited and unedited datasets for the 34 regions of interest (ROIs) that FreeSurfer (FS) generates. To determine whether applying control points would alter the detection of significant differences between patient and typical groups, effect sizes between edited and unedited conditions in individuals with the genetic disorder, 22q11.2 deletion syndrome (22q11DS) were compared to neurotypical controls. Analyses were conducted with data that were generated from both a 1.5 tesla and a 3 tesla scanner. For 1.5 tesla data, mean area, volume, and thickness measures did not differ significantly between edited and unedited regions, with the exception of rostral anterior cingulate thickness, lateral orbitofrontal white matter, superior parietal white matter, and precentral gyral thickness. Results were similar for surface area and white matter volumes generated from the 3 tesla scanner. For cortical thickness measures however, seven edited ROI measures, primarily in frontal and temporal regions, differed significantly from their unedited counterparts, and three additional ROI measures approached significance. Mean effect sizes for edited ROIs did not differ from most unedited ROIs for either 1.5 or 3 tesla data. Taken together, these results suggest that although the application of control points may increase the validity of intensity normalization and, ultimately, segmentation, it may not affect the final, extracted metrics that FS generates. Potential exceptions to and limitations of these conclusions are discussed. PMID- 26539077 TI - VPS54 and the wobbler mouse. AB - The wobbler mouse is an animal model for human motor neuron disease, such as amyotrophic lateral sclerosis (ALS). The spontaneous, recessive wobbler mutation causes degeneration of upper and lower motor neurons leading to progressive muscle weakness with striking similarities to the ALS pathology. The wobbler mutation is a point mutation affecting Vps54, a component of the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a ubiquitously expressed Golgi-localized vesicle tethering complex, tethering endosome-derived vesicles to the trans Golgi network. The wobbler point mutation leads to a destabilization of the Vps54 protein and thereby the whole GARP complex. This effectuates impairments of the retrograde vesicle transport, mis-sorting of Golgi- and endosome localized proteins and on the long run defects in Golgi morphology and function. It is currently largely unknown how the destabilization of the GARP complex interferes with the pathological hallmarks, reported for the wobbler motor neuron degeneration, like neurofilament aggregation, axonal transport defects, hyperexcitability, mitochondrial dysfunction, and how these finally lead to motor neuron death. However, the impairments of the retrograde vesicle transport and the Golgi-function appear to be critical phenomena in the molecular pathology of the wobbler motor neuron disease. PMID- 26539078 TI - Optically transparent multi-suction electrode arrays. AB - Multielectrode arrays (MEAs) allow for acquisition of multisite electrophysiological activity with submillisecond temporal resolution from neural preparations. The signal to noise ratio from such arrays has recently been improved by substrate perforations that allow negative pressure to be applied to the tissue; however, such arrays are not optically transparent, limiting their potential to be combined with optical-based technologies. We present here multi suction electrode arrays (MSEAs) in quartz that yield a substantial increase in the detected number of units and in signal to noise ratio from mouse cortico hippocampal slices and mouse retina explants. This enables the visualization of stronger cross correlations between the firing rates of the various sources. Additionally, the MSEA's transparency allows us to record voltage sensitive dye activity from a leech ganglion with single neuron resolution using widefield microscopy simultaneously with the electrode array recordings. The combination of enhanced electrical signals and compatibility with optical-based technologies should make the MSEA a valuable tool for investigating neuronal circuits. PMID- 26539079 TI - Network-driven design principles for neuromorphic systems. AB - Synaptic connectivity is typically the most resource-demanding part of neuromorphic systems. Commonly, the architecture of these systems is chosen mainly on technical considerations. As a consequence, the potential for optimization arising from the inherent constraints of connectivity models is left unused. In this article, we develop an alternative, network-driven approach to neuromorphic architecture design. We describe methods to analyse performance of existing neuromorphic architectures in emulating certain connectivity models. Furthermore, we show step-by-step how to derive a neuromorphic architecture from a given connectivity model. For this, we introduce a generalized description for architectures with a synapse matrix, which takes into account shared use of circuit components for reducing total silicon area. Architectures designed with this approach are fitted to a connectivity model, essentially adapting to its connection density. They are guaranteeing faithful reproduction of the model on chip, while requiring less total silicon area. In total, our methods allow designers to implement more area-efficient neuromorphic systems and verify usability of the connectivity resources in these systems. PMID- 26539080 TI - Association between polymorphisms in NOS3 and KCNH2 and social memory. AB - Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter individual differences in social memory was investigated in an exploratory sample (n = 55), genotyped with a chip comprising approximately 200,000 single nucleotide polymorphisms (SNPs), and in a validation sample (n = 582), where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition). In the exploratory study, the 30 SNPs that were associated with face recognition at p uncorrected < 0.001 and located in genes, were chosen for further study. In the validation study two of these SNPs showed significant associations with recognition of faces, vocal sounds, and multimodal stimuli: rs1800779 in the gene encoding nitric oxide synthase 3 (NOS3) and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2), in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p < 0.0002). The exploratory study also showed a weaker but significant association with (non emotional) word recognition, an effect that was independent of the effect on face recognition. This study demonstrates evidence for an association between NOS3 and KCNH2 SNPs and social memory. PMID- 26539082 TI - Editorial: Towards an integrated approach to measurement, analysis and modeling of cortical networks. PMID- 26539081 TI - Ion dynamics during seizures. AB - Changes in membrane voltage brought about by ion fluxes through voltage and transmitter-gated channels represent the basis of neural activity. As such, electrochemical gradients across the membrane determine the direction and driving force for the flow of ions and are therefore crucial in setting the properties of synaptic transmission and signal propagation. Ion concentration gradients are established by a variety of mechanisms, including specialized transporter proteins. However, transmembrane gradients can be affected by ionic fluxes through channels during periods of elevated neural activity, which in turn are predicted to influence the properties of on-going synaptic transmission. Such activity-induced changes to ion concentration gradients are a feature of both physiological and pathological neural processes. An epileptic seizure is an example of severely perturbed neural activity, which is accompanied by pronounced changes in intracellular and extracellular ion concentrations. Appreciating the factors that contribute to these ion dynamics is critical if we are to understand how a seizure event evolves and is sustained and terminated by neural tissue. Indeed, this issue is of significant clinical importance as status epilepticus-a type of seizure that does not stop of its own accord-is a life-threatening medical emergency. In this review we explore how the transmembrane concentration gradient of the six major ions (K(+), Na(+), Cl(-), Ca(2+), H(+)and [Formula: see text]) is altered during an epileptic seizure. We will first examine each ion individually, before describing how multiple interacting mechanisms between ions might contribute to concentration changes and whether these act to prolong or terminate epileptic activity. In doing so, we will consider how the availability of experimental techniques has both advanced and restricted our ability to study these phenomena. PMID- 26539084 TI - Mapping the mosaic sequence of primate visual cortical development. AB - Traditional "textbook" theory suggests that the development and maturation of visual cortical areas occur as a wave from V1. However, more recent evidence would suggest that this is not the case, and the emergence of extrastriate areas occurs in a non-hierarchical fashion. This proposition comes from both physiological and anatomical studies but the actual developmental sequence of extrastriate areas remains unknown. In the current study, we examined the development and maturation of the visual cortex of the marmoset monkey, a New World simian, from embryonic day 130 (15 days prior to birth) through to adulthood. Utilizing the well-described expression characteristics of the calcium binding proteins calbindin and parvalbumin, and nonphosphorylated neurofilament for the pyramidal neurons, we were able to accurately map the sequence of development and maturation of the visual cortex. To this end, we demonstrated that both V1 and middle temporal area (MT) emerge first and that MT likely supports dorsal stream development while V1 supports ventral stream development. Furthermore, the emergence of the dorsal stream-associated areas was significantly earlier than ventral stream areas. The difference in the temporal development of the visual streams is likely driven by a teleological requirement for specific visual behavior in early life. PMID- 26539085 TI - Visual mislocalization during double-step saccades. AB - Visual objects presented briefly at the time of saccade onset appear compressed toward the saccade target. Compression strength depends on the presentation of a visual saccade target signal and is strongly reduced during the second saccade of a double-step saccade sequence (Zimmermann et al., 2014b). Here, I tested whether perisaccadic compression is linked to saccade planning by contrasting two double step paradigms. In the same-direction double-step paradigm, subjects were required to perform two rightward 10 degrees saccades successively. At various times around execution of the saccade sequence a probe dot was briefly flashed. Subjects had to localize the position of the probe dot after they had completed both saccades. I found compression of visual space only at the time of the first but not at the time of the second saccade. In the reverse-direction paradigm, subjects performed first a rightward 10 degrees saccade followed by a leftward 10 degrees saccade back to initial fixation. In this paradigm compression was found in similar magnitude during both saccades. Analysis of the saccade parameters did not reveal indications of saccade sequence preplanning in this paradigm. I therefore conclude that saccade planning, rather than saccade execution factors, is involved in perisaccadic compression. PMID- 26539083 TI - Monoaminergic tone supports conductance correlations and stabilizes activity features in pattern generating neurons of the lobster, Panulirus interruptus. AB - Experimental and computational studies demonstrate that different sets of intrinsic and synaptic conductances can give rise to equivalent activity patterns. This is because the balance of conductances, not their absolute values, defines a given activity feature. Activity-dependent feedback mechanisms maintain neuronal conductance correlations and their corresponding activity features. This study demonstrates that tonic nM concentrations of monoamines enable slow, activity-dependent processes that can maintain a correlation between the transient potassium current (I(A) and the hyperpolarization activated current (Ih) over the long-term (i.e., regulatory change persists for hours after removal of modulator). Tonic 5 nM DA acted through an RNA interference silencing complex (RISC)- and RNA polymerase II-dependent mechanism to maintain a long-term positive correlation between I(A) and Ih in the lateral pyloric neuron (LP) but not in the pyloric dilator neuron (PD). In contrast, tonic 5 nM 5HT maintained a RISC-dependent positive correlation between I(A) and Ih in PD but not LP over the long-term. Tonic 5 nM OCT maintained a long-term negative correlation between I(A) and Ih in PD but not LP; however, it was only revealed when RISC was inhibited. This study also demonstrated that monoaminergic tone can also preserve activity features over the long-term: the timing of LP activity, LP duty cycle and LP spike number per burst were maintained by tonic 5 nM DA. The data suggest that low-level monoaminergic tone acts through multiple slow processes to permit cell-specific, activity-dependent regulation of ionic conductances to maintain conductance correlations and their corresponding activity features over the long term. PMID- 26539087 TI - Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY). AB - Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. PMID- 26539086 TI - Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals. AB - The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. PMID- 26539088 TI - Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models. AB - Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models. PMID- 26539089 TI - A subject-independent pattern-based Brain-Computer Interface. AB - While earlier Brain-Computer Interface (BCI) studies have mostly focused on modulating specific brain regions or signals, new developments in pattern classification of brain states are enabling real-time decoding and modulation of an entire functional network. The present study proposes a new method for real time pattern classification and neurofeedback of brain states from electroencephalographic (EEG) signals. It involves the creation of a fused classification model based on the method of Common Spatial Patterns (CSPs) from data of several healthy individuals. The subject-independent model is then used to classify EEG data in real-time and provide feedback to new individuals. In a series of offline experiments involving training and testing of the classifier with individual data from 27 healthy subjects, a mean classification accuracy of 75.30% was achieved, demonstrating that the classification system at hand can reliably decode two types of imagery used in our experiments, i.e., happy emotional imagery and motor imagery. In a subsequent experiment it is shown that the classifier can be used to provide neurofeedback to new subjects, and that these subjects learn to "match" their brain pattern to that of the fused classification model in a few days of neurofeedback training. This finding can have important implications for future studies on neurofeedback and its clinical applications on neuropsychiatric disorders. PMID- 26539090 TI - Learning about time within the spinal cord: evidence that spinal neurons can abstract and store an index of regularity. AB - Prior studies have shown that intermittent noxious stimulation has divergent effects on spinal cord plasticity depending upon whether it occurs in a regular (fixed time, FT) or irregular (variable time, VT) manner: In spinally transected animals, VT stimulation to the tail or hind leg impaired spinal learning whereas an extended exposure to FT stimulation had a restorative/protective effect. These observations imply that lower level systems are sensitive to temporal relations. Using spinally transected rats, it is shown that the restorative effect of FT stimulation emerges after 540 shocks; fewer shocks generate a learning impairment. The transformative effect of FT stimulation is related to the number of shocks administered, not the duration of exposure. Administration of 360 FT shocks induces a learning deficit that lasts 24 h. If a second bout of FT stimulation is given a day after the first, it restores the capacity to learn. This savings effect implies that the initial training episode had a lasting (memory-like) effect. Two bouts of shock have a transformative effect when applied at different locations or at difference frequencies, implying spinal systems abstract and store an index of regularity (rather than a specific interval). Implications of the results for step training and rehabilitation after injury are discussed. PMID- 26539091 TI - Mouse hippocampal GABAB1 but not GABAB2 subunit-containing receptor complex levels are paralleling retrieval in the multiple-T-maze. AB - GABAB receptors are heterodimeric G-protein coupled receptors known to be involved in learning and memory. Although a role for GABAB receptors in cognitive processes is evident, there is no information on hippocampal GABAB receptor complexes in a multiple T maze (MTM) task, a robust paradigm for evaluation of spatial learning. Trained or untrained (yoked control) C57BL/6J male mice (n = 10/group) were subjected to the MTM task and sacrificed 6 h following their performance. Hippocampi were taken, membrane proteins extracted and run on blue native PAGE followed by immunoblotting with specific antibodies against GABAB1, GABAB1a, and GABAB2. Immunoprecipitation with subsequent mass spectrometric identification of co-precipitates was carried out to show if GABAB1 and GABAB2 as well as other interacting proteins co-precipitate. An antibody shift assay (ASA) and a proximity ligation assay (PLA) were also used to see if the two GABAB subunits are present in the receptor complex. Single bands were observed on Western blots, each representing GABAB1, GABAB1a, or GABAB2 at an apparent molecular weight of approximately 100 kDa. Subsequently, densitometric analysis revealed that levels of GABAB1 and GABAB1a but not GABAB2- containing receptor complexes were significantly higher in trained than untrained groups. Immunoprecipitation followed by mass spectrometric studies confirmed the presence of GABAB1, GABAB2, calcium calmodulin kinases I and II, GluA1 and GluA2 as constituents of the complex. ASA and PLA also showed the presence of the two subunits of GABAB receptor within the complex. It is shown that increased levels of GABAB1 subunit-containing complexes are paralleling performance in a land maze. PMID- 26539092 TI - Longitudinal maturation of auditory cortical function during adolescence. AB - Cross-sectional studies have demonstrated that the cortical auditory evoked potential (CAEP) changes substantially in amplitude and latency from childhood to adulthood, suggesting that these aspects of the CAEP continue to mature through adolescence. However, no study to date has longitudinally followed maturation of these CAEP measures through this developmental period. Additionally, no study has examined the trial-to-trial variability of the CAEP during adolescence. Therefore, we longitudinally tracked changes in the latency, amplitude, and variability of the P1, N1, P2, and N2 components of the CAEP in 68 adolescents from age 14 years to age 17 years. Latency decreased for N1 and N2, and did not change for P1 or P2. Amplitude decreased for P1 and N2, increased for N1, and did not change for P2. Variability decreased with age for all CAEP components. These findings provide longitudinal support for the view that the human auditory system continues to mature through adolescence. Continued auditory system maturation through adolescence suggests that CAEP neural generators remain plastic during this age range and potentially amenable to experience-based enhancement or deprivation. PMID- 26539093 TI - The effects of cardiorespiratory fitness and acute aerobic exercise on executive functioning and EEG entropy in adolescents. AB - The current study examined the effects of cardiorespiratory fitness, identified with a continuous graded cycle ergometry, and aerobic exercise on cognitive functioning and entropy of the electroencephalogram (EEG) in 30 adolescents between the ages of 13 and 14 years. Higher and lower fit participants performed an executive function task after a bout of acute exercise and after rest while watching a film. EEG entropy, using the sample entropy measure, was repeatedly measured during the 1500 ms post-stimulus interval to evaluate changes in entropy over time. Analysis of the behavioral data for lower and higher fit groups revealed an interaction between fitness levels and acute physical exercise. Notably, lower fit, but not higher fit, participants had higher error rates (ER) for No Go relative to Go trials in the rest condition, whereas in the acute exercise condition there were no differences in ER between groups; higher fit participants also had significantly faster reaction times in the exercise condition in comparison with the rest condition. Analysis of EEG data revealed that higher fit participants demonstrated lower entropy post-stimulus than lower fit participants in the left frontal hemisphere, possibly indicating increased efficiency of early stage stimulus processing and more efficient allocation of cognitive resources to the task demands. The results suggest that EEG entropy is sensitive to stimulus processing demands and varies as a function of physical fitness levels, but not acute exercise. Physical fitness, in turn, may enhance cognition in adolescence by facilitating higher functionality of the attentional system in the context of lower levels of frontal EEG entropy. PMID- 26539094 TI - Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex. AB - "Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning. PMID- 26539095 TI - Perceptual task induces saccadic adaptation by target selection. AB - Adaptation of saccades can be induced by different error signals, such as retinal position errors, prediction errors, or reinforcement learning. Recently, we showed that a shift in the spatial goal of a perceptual task can induce saccadic adaptation, in the absence of a bottom-up position error. Here, we investigated whether this top-down effect is mediated by the visibility of the task-relevant object, by reinforcement due to the feedback about the perceptual judgment or by a target selection mechanism. Participants were asked to discriminate visual stimuli arranged in a vertical compound. To induce adaptation, the discrimination target was presented at eccentric locations in the compound. In the first experiment, we compared adaptation with an easy and difficult discrimination. In the second experiment, we compared adaptation when feedback about the perceptual task was valid and when feedback was provided but was unrelated to performance. In the third experiment, we compared adaptation with instructions to fixate one of the elements in the compound-target selection-to the perceptual task condition target selection and discrimination. To control for a bottom-up stimulus effect, we ran a fourth experiment in which the only instruction was to look at the compound. The saccade amplitude data were fitted by a two-state model distinguishing between an immediate and a gradual error correction process. We replicated our finding that a perceptual task can drive adaptation of saccades. Adaptation showed no effect of feedback reliability, nor an effect of the perceptual task beyond target selection. Adaptation was induced by a top-down signal since it was absent when there was no target selection instruction and no perceptual task. The immediate error correction was larger for the difficult than for the easy condition, suggesting that task difficulty affects mainly voluntary saccade targeting. In addition, the repetition of experiments one week later increased the magnitude of the gradual error correction. The results dissociate two distinct components of adaptation: an immediate and a gradual error correction. We conclude that perceptual-task induced adaptation is most likely due to top-down target selection within a larger object. PMID- 26539096 TI - Identifying environmental sounds: a multimodal mapping study. AB - Our environment is full of auditory events such as warnings or hazards, and their correct recognition is essential. We explored environmental sounds (ES) recognition in a series of studies. In study 1 we performed an Activation Likelihood Estimation (ALE) meta-analysis of neuroimaging experiments addressing ES processing to delineate the network of areas consistently involved in ES processing. Areas consistently activated in the ALE meta-analysis were the STG/MTG, insula/rolandic operculum, parahippocampal gyrus and inferior frontal gyrus bilaterally. Some of these areas truly reflect ES processing, whereas others are related to design choices, e.g., type of task, type of control condition, type of stimulus. In study 2 we report on 7 neurosurgical patients with lesions involving the areas which were found to be activated by the ALE meta analysis. We tested their ES recognition abilities and found an impairment of ES recognition. These results indicate that deficits of ES recognition do not exclusively reflect lesions to the right or to the left hemisphere but both hemispheres are involved. The most frequently lesioned area is the hippocampus/insula/STG. We made sure that any impairment in ES recognition would not be related to language problems, but reflect impaired ES processing. In study 3 we carried out an fMRI study on patients (vs. healthy controls) to investigate how the areas involved in ES might be functionally deregulated because of a lesion. The fMRI evidenced that controls activated the right IFG, the STG bilaterally and the left insula. We applied a multimodal mapping approach and found that, although the meta-analysis showed that part of the left and right STG/MTG activation during ES processing might in part be related to design choices, this area was one of the most frequently lesioned areas in our patients, thus highlighting its causal role in ES processing. We found that the ROIs we drew on the two clusters of activation found in the left and in the right STG overlapped with the lesions of at least 4 out of the 7 patients' lesions, indicating that the lack of STG activation found for patients is related to brain damage and is crucial for explaining the ES deficit. PMID- 26539098 TI - When ultrarapid is ultrarapid: on importance of temporal precision in neuroscience of language. PMID- 26539097 TI - High-frequency oscillations in epilepsy and surgical outcome. A meta-analysis. AB - High frequency oscillations (HFOs) are estimated as a potential marker for epileptogenicity. Current research strives for valid evidence that these HFOs could aid the delineation of the to-be resected area in patients with refractory epilepsy and improve surgical outcomes. In the present meta-analysis, we evaluated the relation between resection of regions from which HFOs can be detected and outcome after epilepsy surgery. We conducted a systematic review of all studies that related the resection of HFO-generating areas to postsurgical outcome. We related the outcome (seizure freedom) to resection ratio, that is, the ratio between the number of channels on which HFOs were detected and, among these, the number of channels that were inside the resected area. We compared the resection ratio between seizure free and not seizure free patients. In total, 11 studies were included. In 10 studies, ripples (80-200 Hz) were analyzed, and in 7 studies, fast ripples (>200 Hz) were studied. We found comparable differences (dif) and largely overlapping confidence intervals (CI) in resection ratios between outcome groups for ripples (dif = 0.18; CI: 0.10-0.27) and fast ripples (dif = 0.17; CI: 0.01-0.33). Subgroup analysis showed that automated detection (dif = 0.22; CI: 0.03-0.41) was comparable to visual detection (dif = 0.17; CI: 0.08-0.27). Considering frequency of HFOs (dif = 0.24; CI: 0.09-0.38) was related more strongly to outcome than considering each electrode that was showing HFOs (dif = 0.15; CI = 0.03-0.27). The effect sizes found in the meta-analysis are small but significant. Automated detection and application of a detection threshold in order to detect channels with a frequent occurrence of HFOs is important to yield a marker that could be useful in presurgical evaluation. In order to compare studies with different methodological approaches, detailed and standardized reporting is warranted. PMID- 26539099 TI - Commentary: Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy. PMID- 26539100 TI - Human visual cortical responses to specular and matte motion flows. AB - Determining the compositional properties of surfaces in the environment is an important visual capacity. One such property is specular reflectance, which encompasses the range from matte to shiny surfaces. Visual estimation of specular reflectance can be informed by characteristic motion profiles; a surface with a specular reflectance that is difficult to determine while static can be confidently disambiguated when set in motion. Here, we used fMRI to trace the sensitivity of human visual cortex to such motion cues, both with and without photometric cues to specular reflectance. Participants viewed rotating blob-like objects that were rendered as images (photometric) or dots (kinematic) with either matte-consistent or shiny-consistent specular reflectance profiles. We were unable to identify any areas in low and mid-level human visual cortex that responded preferentially to surface specular reflectance from motion. However, univariate and multivariate analyses identified several visual areas; V1, V2, V3, V3A/B, and hMT+, capable of differentiating shiny from matte surface flows. These results indicate that the machinery for extracting kinematic cues is present in human visual cortex, but the areas involved in integrating such information with the photometric cues necessary for surface specular reflectance remain unclear. PMID- 26539101 TI - Direct comparisons of hand and mouth kinematics during grasping, feeding and fork feeding actions. AB - While a plethora of studies have examined the kinematics of human reach-to-grasp actions, few have investigated feeding, another ethologically important real world action. Two seminal studies concluded that the kinematics of the mouth during feeding are comparable to those of the hand during grasping (Castiello, 1997; Churchill et al., 1999); however, feeding was done with a fork or spoon, not with the hand itself. Here, we directly compared grasping and feeding kinematics under equivalent conditions. Participants were presented with differently sized cubes of cheese (10-, 20- or 30-mm on each side) and asked to use the hand to grasp them or to use a fork to spear them and then bring them to the mouth to bite. We measured the apertures of the hand during grasping and the teeth during feeding, as well as reaching kinematics of the arm in both tasks. As in many past studies, we found that the hand oversized considerably larger (~11 27 mm) than the food item during grasping; moreover, the amount of oversizing scaled with food size. Surprisingly, regardless of whether the hand or fork was used to transport the food, the mouth oversized only slightly larger (~4-11 mm) than the food item during biting and the oversizing did not increase with food size. Total movement times were longer when using the fork compared to the hand, particularly when using the fork to bring food to the mouth. While reach velocity always peaked approximately halfway through the movement, relative to the reach the mouth opened more slowly than the hand, perhaps because less time was required for the smaller oversizing. Taken together, our results show that while many aspects of kinematics share some similarity between grasping and feeding, oversizing may reflect strategies unique to the hand vs. mouth (such as the need to have the digits approach the target surface perpendicularly for grip stability during lifting) and differences in the neural substrates of grasping and feeding. PMID- 26539102 TI - Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair. AB - Researchers are enthusiastically concerned about neural stem cell (NSC) therapy in a wide array of diseases, including stroke, neurodegenerative disease, spinal cord injury, and depression. Although enormous evidences have demonstrated that neurobehavioral improvement may benefit from NSC-supporting regeneration in animal models, approaches to endogenous and transplanted NSCs are blocked by hurdles of migration, proliferation, maturation, and integration of NSCs. Electrical stimulation (ES) may be a selective non-drug approach for mobilizing NSCs in the central nervous system. This technique is suitable for clinical application, because it is well established and its potential complications are manageable. Here, we provide a comprehensive review of the emerging positive role of different electrical cues in regulating NSC biology in vitro and in vivo, as well as biomaterial-based and chemical stimulation of NSCs. In the future, ES combined with stem cell therapy or other cues probably becomes an approach for promoting brain repair. PMID- 26539103 TI - Limitations of short range Mexican hat connection for driving target selection in a 2D neural field: activity suppression and deviation from input stimuli. AB - Dynamic Neural Field models (DNF) often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take all processes such as saliency localization, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC), a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs) exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted toward the strongest stimulus, reminiscent of well known behavioral data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although, those properties call for systematic testing, the discussion gathers neurophysiological and behavioral data suggesting that such properties are indeed present in target selection for saccadic eye movements. PMID- 26539105 TI - Neural field simulator: two-dimensional spatio-temporal dynamics involving finite transmission speed. AB - Neural Field models (NFM) play an important role in the understanding of neural population dynamics on a mesoscopic spatial and temporal scale. Their numerical simulation is an essential element in the analysis of their spatio-temporal dynamics. The simulation tool described in this work considers scalar spatially homogeneous neural fields taking into account a finite axonal transmission speed and synaptic temporal derivatives of first and second order. A text-based interface offers complete control of field parameters and several approaches are used to accelerate simulations. A graphical output utilizes video hardware acceleration to display running output with reduced computational hindrance compared to simulators that are exclusively software-based. Diverse applications of the tool demonstrate breather oscillations, static and dynamic Turing patterns and activity spreading with finite propagation speed. The simulator is open source to allow tailoring of code and this is presented with an extension use case. PMID- 26539106 TI - Memory impairment in older adults' diversionary thoughts. AB - The diversion paradigm was created in the context of explaining the effect of the instruction to forget some recently encoded material in the list-method of the directed forgetting paradigm. The current study of healthy older adults employed the diversion paradigm with two main goals: to determine whether thinking about an autobiographical memory interferes with the recall of recently encoded information and to explore whether the degree of forgetting depends on the temporal distance created by the diversionary thought. Ninety non institutionalized Portuguese older adults (47 females and 43 males), aged 65-69 years, with education levels of between 3 and 6 years participated in this study. The exclusion criteria were as follows: presence of depressive symptomatology (assessed with the Geriatric Depression Scale-30) and global cognitive deterioration (assessed with the Mini-Mental State Examination). Concerning the diversion paradigm, one group was instructed to think about an autobiographical event (remembering one's childhood home or the last party that one had attended) after studying one word list (List 1) and before viewing the second word list (List 2). After a brief distraction task, the participant had to recall the words from both of the studied lists. In the control group, the procedure was the same, but the diversionary thought was substituted by a speed reading task. The obtained results showed the amnesic effect of diversionary thought but did not show a greater degree of forgetting when the autobiographical events in the diversionary thoughts were temporally more distant. Considering the practical implications of these results, this study alerts us to the importance of promoting strategies that enable older adults to better remember important information and effectively forget irrelevant information. PMID- 26539104 TI - The 40-year history of modeling active dendrites in cerebellar Purkinje cells: emergence of the first single cell "community model". AB - The subject of the effects of the active properties of the Purkinje cell dendrite on neuronal function has been an active subject of study for more than 40 years. Somewhat unusually, some of these investigations, from the outset have involved an interacting combination of experimental and model-based techniques. This article recounts that 40-year history, and the view of the functional significance of the active properties of the Purkinje cell dendrite that has emerged. It specifically considers the emergence from these efforts of what is arguably the first single cell "community" model in neuroscience. The article also considers the implications of the development of this model for future studies of the complex properties of neuronal dendrites. PMID- 26539107 TI - Speaking in Alzheimer's Disease, is That an Early Sign? Importance of Changes in Language Abilities in Alzheimer's Disease. AB - It is known that Alzheimer's disease (AD) influences the temporal characteristics of spontaneous speech. These phonetical changes are present even in mild AD. Based on this, the question arises whether an examination based on language analysis could help the early diagnosis of AD and if so, which language and speech characteristics can identify AD in its early stage. The purpose of this article is to summarize the relation between prodromal and manifest AD and language functions and language domains. Based on our research, we are inclined to claim that AD can be more sensitively detected with the help of a linguistic analysis than with other cognitive examinations. The temporal characteristics of spontaneous speech, such as speech tempo, number of pauses in speech, and their length are sensitive detectors of the early stage of the disease, which enables an early simple linguistic screening for AD. However, knowledge about the unique features of the language problems associated with different dementia variants still has to be improved and refined. PMID- 26539108 TI - Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults. AB - Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (rho = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, -0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer's disease (AD) pathology (Estimate, -0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (-0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID- 26539109 TI - Chemical Exchange Saturation Transfer MR Imaging is Superior to Diffusion-Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: A Study on Substantia Nigra and Striatum. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date, the diagnosis of PD is still based primarily on the clinical manifestations, which may be typical and obvious only in advanced stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical exchange saturation transfer (CEST) imaging and diffusion-tensor imaging (DTI) in PD at 3 T by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3-T MR system, using an eight-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization transfer ratio asymmetry at 3.5 ppm, MTRasym(3.5 ppm), and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen, and caudate. The MTRasym(3.5 ppm) value, the total CEST signal intensity, and fractional anisotropy value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004, and P < 0.001, respectively). The MTRasym(3.5 ppm) values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively). There were no significant differences for the mean diffusivity in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD. PMID- 26539110 TI - Abeta Clearance, "hub" of Multiple Deficiencies Leading to Alzheimer Disease. PMID- 26539111 TI - Older adults can improve compensatory stepping with repeated postural perturbations. AB - The ability to respond quickly and accurately to an external perturbation with a stepping response is critical to avoid falls and this ability is impaired in older, compared to young adults. However, little is known about whether young and older adults improve compensatory stepping responses similarly with practice. This study compares the extent to which young and older adults can improve, retain, and generalize postural compensatory steps in response to external perturbations. Centre of mass displacement, step characteristics and lower leg muscle activation latencies were measured during one training session of compensatory stepping in response to large surface translations in 13 young and 12 older adults. Retention was tested 24 h later. Older adults decreased their center of mass displacements over repeated exposure to large surface translations in both the anterior and posterior directions and retained these improvements. In contrast, young adults only showed adaptation and retention of forward stepping responses. Neither group was able to generalize improvements in stepping responses across directions. These results suggest step training may be beneficial for older adults, however additional, multidirectional training may be necessary to facilitate generalization of postural stepping responses for any direction of a slip or trip. PMID- 26539112 TI - PGC-1alpha Silencing Compounds the Perturbation of Mitochondrial Function Caused by Mutant SOD1 in Skeletal Muscle of ALS Mouse Model. AB - Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease causing death of motor neurons. This study investigated the roles of energy metabolism in the pathogenesis of ALS in the SOD1(G93A) transgenic mouse model. Control and SOD1(G93A) mice were administered with shcontrol or shPGC-1alpha in combination with PBS or thiazolidinedione (TZD) for 8 weeks. Gene expression was analyzed by quantitative real-time PCR and Western blot. ROS and fibrosis were assessed with a colorimetric kit and Sirius staining, respectively. Inflammatory cytokines were measured using ELISA kits. The levels of tissue ROS and serum inflammatory cytokines were significantly higher in SOD1(G93A) mice compared to control mice, and knocking down peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) drastically increased cytokine levels in both control and SOD1(G93A) mice. Muscle fibrosis was much severer in SOD1(G93A) mice, and worsened by silencing PGC-1alpha and attenuated by TZD. The expression levels of PGC-1alpha, SOD1, UCP2, and cytochrome C were substantially reduced by shPGC 1alpha and increased by TZD in muscle of both control and SOD1(G93A) mice, whereas the level of NF-kappaB was significantly elevated in SOD1(G93A) mice, which was further increased by PGC-1alpha silencing. These data indicated that disruption of energy homeostasis would exacerbate the pathological changes caused by SOD1 mutations to promote the pathogenesis of ALS. PMID- 26539114 TI - Commentary: The sphingosine kinase 1/sphingosine-1-phosphate pathway in pulmonary arterial hypertension. PMID- 26539113 TI - Cardiovascular imaging: what have we learned from animal models? AB - Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models. PMID- 26539116 TI - Nutrition and health technology assessment: when two worlds meet. AB - There is a growing recognition that nutrition may have a positive impact on public health and that it may reduce medical expenditures. Yet, such claims need to be substantiated by evidence. This evidence could be delivered by health technology assessment (HTA), which can be thought of as the evaluation of technologies for clinical effectiveness, cost-effectiveness, and ethical, legal, and social impacts. The application of HTA to the field of "nutrition interventions" is recent. So far, HTA and nutrition have represented two worlds far apart in many respects. This contribution, roughly, addresses the following issues: is there a need for HTAs in the field of nutrition, what would such HTAs look like, and how can the results coming from these HTAs optimally aid policy making? In essence, HTAs of nutrition have much of the same basic principles and structure as HTAs of "classical" health care treatments. Nevertheless, there are challenges to rigorous HTAs of nutrition interventions, for various reasons. To mention a few: the evidence base for nutrition interventions is less well developed than that for many health care treatments. Furthermore, it is a matter of debate which outcome measures should be used in HTAs of nutrition. For example, one may argue that nutrition not only has health effects, but also effects that are not captured by traditional health-related quality of life measures (e.g., the pleasure of eating, effects relating to ease of use, or effects on well-being). HTAs in the field of nutrition may deliver information valuable to a wide range of stakeholders, including consumers/patients, health professionals, hospital administrators, insurers, and decision makers. The results of HTAs are typically used in making treatment guidelines, in informing decisions about reimbursement or about public health campaigns, etc. Yet, it is uncertain how the results of HTAs of nutrition can be used optimally. For example, would it be possible to summarize the results of a HTA in a single ratio (such as costs per quality-adjusted life-year gained) and then to either approve or reject the intervention based on this ratio, compared to a certain threshold? Apart from that, in the field of nutrition, it is typically not about reimbursement of a technology. Related to this, it is important that the message from HTAs of nutrition is brought to a range of stakeholders including the general population and that these HTAs are tailored to the decision-making context. To conclude, a growing need is felt for HTA-type evaluations of nutrition, which are sparse these days. Little thought has been given to developing an optimal methodology for HTAs of nutrition and to how its results should be integrated into policy making. Further work in these areas would stimulate the development of nutrition interventions that yield a gain in societal welfare. To achieve this, the two worlds of HTA and nutrition need to be brought together. PMID- 26539115 TI - The power of using functional fMRI on small rodents to study brain pharmacology and disease. AB - Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal's physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations. PMID- 26539117 TI - Integrated expression profiles of mRNA and microRNA in the liver of Fructus Meliae Toosendan water extract injured mice. AB - Liver toxicity is a severe problem associated with Traditional Chinese Medicine (TCM). Fructus Meliae Toosendan (FMT) is a known hepatotoxic TCM, however, the toxicological mechanisms of liver injury caused by FMT treatment still remain largely unknown. In this study, we aimed to reveal possible mechanisms of FMT water extract-induced liver injury using a systemic approach. After three consecutive daily dosing of FMT water extract, significant increases of alanine transaminase, aspartate transaminase, and alkaline phosphatase activities, along with elevated total bilirubin and total cholesterol levels and a decrease of triglyceride level, were detected in mice serum. Moreover, hydropic degeneration was observed in hepatocytes, suggesting the presence of FMT-induced liver injury. mRNA and microRNA expression profiles of liver samples from injured mice were analyzed and revealed 8 miRNAs and 1,723 mRNAs were significantly changed after FMT water extract treatment. For the eight differentially expressed miRNAs, their predicted target genes were collected and a final set of 125 genes and 4 miRNAs (miR-139-5p, miR-199a-5p, miR-2861, and miR-3960) was selected to investigate important processes involved in FMT hepatotoxicity. Our results demonstrated several cellular functions were disordered after FMT treatment, such as cellular growth and proliferation, gene expression and cellular development. We hypothesized that liver cell necrosis was the main liver toxicity of FMT water extract, which was possibly caused by oxidative stress responses. PMID- 26539118 TI - Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells. AB - Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical parameters (lipid accumulation, extent of oxidative stress and release of inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked steatosis in vitro were measured and compared with the control. It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs). The content of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased respectively by nuciferine and siRNA PASK without increase in glutathione (GSH). Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further investigation revealed that nuciferine and siRNA PASK could respectively regulate the expression of target genes involved in lipogenesis and inflammation, suggesting that nuciferine may be a potential therapeutic treatment for NAFLD. Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells lipogenesis and inflammation, which was accompanied with PASK inhibition, was also consistent with siRNA PASK, implying that PASK might play a role in nuciferine-mediated regulation on NAFLD. PMID- 26539119 TI - Blockade of cholinergic transmission elicits somatic signs in nicotine-naive adolescent rats. AB - High doses of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine can elicit somatic signs resembling those associated with nicotine withdrawal in nicotine-naive adult rats. Understanding this phenomenon, and its possible modulation by acute nicotine and age, could inform the use of mecamylamine as both an experimental tool and potential pharmacotherapy for tobacco dependence and other disorders. This study evaluated the ability of high dose mecamylamine to elicit somatic signs in adolescent rats, and the potential for acute nicotine pretreatment to potentiate this effect as previously reported in adults. Single or repeated injections of mecamylamine (1.5 or 3.0 mg/kg, s.c.) elicited somatic signs in nicotine-naive adolescents, but this effect was not influenced by 2 h pretreatment with acute nicotine (0.5 mg/kg, s.c.). In an initial evaluation of the effects of age in this model, mecamylamine (2.25 mg/kg, s.c.) elicited somatic signs in nicotine-naive adolescents and adults. This effect was modestly enhanced following acute nicotine injections in adults but not in adolescents, even when a higher nicotine dose (1.0 rather than 0.5 mg/kg, s.c.) was used in adolescents to account for age differences in nicotine pharmacokinetics. These studies are the first to show that mecamylamine elicits somatic signs in nicotine-naive adolescent rats, an effect that should be considered when designing and interpreting studies examining effects of high doses of mecamylamine in adolescents. Our findings also provide preliminary evidence that these signs may be differentially modulated by acute nicotine pretreatment in adolescents versus adults. PMID- 26539120 TI - Syntenin controls migration, growth, proliferation, and cell cycle progression in cancer cells. AB - The scaffold protein syntenin abounds during fetal life where it is important for developmental movements. In human adulthood, syntenin gain-of-function is increasingly associated with various cancers and poor prognosis. Depending on the cancer model analyzed, syntenin affects various signaling pathways. We previously have shown that syntenin allows syndecan heparan sulfate proteoglycans to escape degradation. This indicates that syntenin has the potential to support sustained signaling of a plethora of growth factors and adhesion molecules. Here, we aim to clarify the impact of syntenin loss-of-function on cancer cell migration, growth, and proliferation, using cells from various cancer types and syntenin shRNA and siRNA silencing approaches. We observed decreased migration, growth, and proliferation of the mouse melanoma cell line B16F10, the human colon cancer cell line HT29 and the human breast cancer cell line MCF7. We further documented that syntenin controls the presence of active beta1 integrin at the cell membrane and G1/S cell cycle transition as well as the expression levels of CDK4, Cyclin D2, and Retinoblastoma proteins. These data confirm that syntenin supports the migration and growth of tumor cells, independently of their origin, and further highlight the attractiveness of syntenin as potential therapeutic target. PMID- 26539123 TI - Editorial: Investigating the human brain and muscle coupling during whole-body challenging exercise. PMID- 26539122 TI - Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine. AB - Both beta adrenergic and muscarinic receptor stimulation independently potentiate arrhythmogenesis. However, the effect of simultaneous stimulation on arrhythmogenesis is not well known. The purpose of this study was to determine the temporal response of arrhythmia risk to individual and combined autonomic agonists. Guinea pig hearts were excised and Langendorff-perfused. The beta adrenergic receptor and muscarinic receptor agonists were isoproterenol (ISO, 0.6 MUM) and acetylcholine (ACh, 10 MUM), respectively. All measurements with agonists occurred over 21 min. ISO induced ectopic activity for the first 8 min. ISO also transiently shortened and then prolonged R-R interval over a similar time course. ACh added after ISO transiently induced ectopic activity for 12 min, while R-R interval invariantly prolonged. ACh alone produced few ectopic beats, while invariantly prolonging R-R interval. In contrast to ISO alone, ISO following ACh significantly increased ectopic activity and shortened R-R interval for the duration of the experiment. Animals aged 17-19 months exhibited sustained arrhythmogenesis while those aged 11-14 did not. When ACh was removed in older hearts while ISO perfused, a transient increase in ectopic activity and decreased R-R interval was observed, similar to ISO alone. These data suggest that pre treating with and maintaining ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone. PMID- 26539121 TI - HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications. AB - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID- 26539124 TI - An integrated finite element simulation of cardiomyocyte function based on triphasic theory. AB - In numerical simulations of cardiac excitation-contraction coupling, the intracellular potential distribution and mobility of cytosol and ions have been mostly ignored. Although the intracellular potential gradient is small, during depolarization it can be a significant driving force for ion movement, and is comparable to diffusion in terms of net flux. Furthermore, fluid in the t-tubules is thought to advect ions to facilitate their exchange with the extracellular space. We extend our previous finite element model that was based on triphasic theory to examine the significance of these factors in cardiac physiology. Triphasic theory allows us to study the behavior of solids (proteins), fluids (cytosol) and ions governed by mechanics and electrochemistry in detailed subcellular structures, including myofibrils, mitochondria, the sarcoplasmic reticulum, membranes, and t-tubules. Our simulation results predicted an electrical potential gradient inside the t-tubules at the onset of depolarization, which corresponded to the Na(+) channel distribution therein. Ejection and suction of fluid between the t-tubules and the extracellular compartment during isometric contraction were observed. We also examined the influence of t-tubule morphology and mitochondrial location on the electrophysiology and mechanics of the cardiomyocyte. Our results confirm that the t-tubule structure is important for synchrony of Ca(2+) release, and suggest that mitochondria in the sub-sarcolemmal region might serve to cancel Ca(2+) inflow through surface sarcolemma, thereby maintaining the intracellular Ca(2+) environment in equilibrium. PMID- 26539125 TI - The influence of platelet-derived products on angiogenesis and tissue repair: a concise update. AB - Platelet degranulation allows the release of a large amount of soluble mediators, is an essential step for wound healing initiation, and stimulates clotting, and angiogenesis. The latter process is one of the most critical biological events observed during tissue repair, increasing the growth of blood vessels in the maturing wound. Angiogenesis requires the action of a variety of growth factors that act in an appropriate physiological ratio to assure functional blood vessel restoration. Platelets release main regulators of angiogenesis: Vascular Endothelial Growth Factors (VEGFs), basic fibroblast growth factor (FGF-2), and Platelet derived growth factors (PDGFs), among others. In order to stimulate tissue repair, platelet derived fractions have been used as an autologous source of growth factors and biomolecules, namely Platelet Rich Plasma (PRP), Platelet Poor Plasma (PPP), and Platelet Rich Fibrin (PRF). The continuous release of these growth factors has been proposed to promote angiogenesis both in vitro and in vivo. Considering the existence of clinical trials currently evaluating the efficacy of autologous PRP, the present review analyses fundamental questions regarding the putative role of platelet derived fractions as regulators of angiogenesis and evaluates the possible clinical implications of these formulations. PMID- 26539126 TI - Cellular and Molecular Inflammatory Profile of the Choroid Plexus in Depression and Suicide. AB - The inflammatory hypothesis of depression is one of the main theories that endeavors to explain and describe the underlying biological mechanisms of depression and suicide. While mounting evidence indicates altered peripheral and central inflammatory profiles in depressed patients and suicide completers, little is known about how peripheral and central inflammation might be linked in these contexts. The choroid plexus (ChP), a highly vascularized tissue that produces cerebrospinal fluid (CSF) and lacks a blood-brain-barrier, is an interface between peripheral and central immune responses. In the present study, we investigated the cellular and molecular inflammatory profile of the ChP of the lateral ventricle in depressed suicides and psychiatrically healthy controls. Gene expression of macrophages, pro- and anti-inflammatory cytokines, and various factors implicated in immune cell trafficking were measured; and density of ionized calcium-binding adaptor molecule 1-positive (Iba1+) macrophages associated with the ChP epithelial cell layer (ECL) was examined. Significant downregulations of the genes encoding interleukin 1beta (IL1beta), a pro inflammatory acute-phase protein; intercellular cell adhesion molecule 1 (ICAM1), a protein implicated in immune cell trafficking in the ChP; and IBA1, a monocyte/macrophage marker; were detected in depressed suicides as compared to controls. No difference in the density of Iba1+ macrophages associated with the ChP ECL was observed. While interpretation of these findings is challenging in the absence of corroborating data from the CSF, peripheral blood, or brain parenchyma of the present cohort, we hypothesize that the present findings reflect a ChP compensatory mechanism that attenuates the detrimental effects of chronically altered pro-inflammatory signaling caused by elevated levels of pro inflammatory cytokines, such as IL-1beta, peripherally and/or centrally. Together, these findings further implicate neuroimmune processes in the etiology of depression and suicide. PMID- 26539127 TI - The Development of a Screening Questionnaire for Obstructive Sleep Apnea in Children with Down Syndrome. AB - Obstructive sleep apnea is a condition which affects an estimated 50% of children with Down syndrome, particularly in their early years. It can cause serious sequelae in affected children but may not be recognized by parents or health professionals. Routine screening has been recommended in some countries, but is not standard practice. There are no validated questionnaire-based tools available to screen this population of children for this particular sleep-related disorder. Using existing validated sleep questionnaire items, we have developed a questionnaire to screen children with Down syndrome up to 6 years of age for obstructive sleep apnea, which corresponds with the recommendations made in UK national guidelines. This paper describes these first steps in demonstrating content validity for a new questionnaire, which will be subject to further in depth psychometric analysis. Relevance, clarity, and age appropriateness were rated for 33 items using a content review questionnaire by a group of 18 health professionals with expertise in respiratory pediatrics, neurodevelopmental pediatrics, and sleep physiology. The content validity index was calculated for individual items and contributed to decisions about item inclusion. Scale level content validity index for the modified questionnaire of 14 items was at an accepted level of 0.78. Two parents of children with Down syndrome took part in cognitive interviews after completing the modified questionnaire. We describe the development of this 14 item questionnaire to screen for OSA in children with DS from infancy to 6 years. PMID- 26539128 TI - Attentional Load Effects on Beta Oscillations in Healthy and Schizophrenic Individuals. AB - Attentional deficits are prominent among the cognitive disturbances found in schizophrenia. Given that schizophrenia is also characterized by abnormalities in high-frequency oscillations, we investigated whether attentional function in schizophrenia is related to abnormalities in high-frequency oscillations in a visual discrimination task in which attentional load was manipulated. Sixteen healthy control subjects (HC) and 23 chronic schizophrenia patients (SZ) discriminated between target discs (p = 0.2) and standard discs (p = 0.8). Attentional load was manipulated by varying the size difference between the target and standard discs across blocks: large (Easy condition), medium (Medium), and small (Difficult). The electroencephalogram was recorded and the oscillations evoked by the standard stimuli were analyzed using the Morlet wavelet transform. Subjects' performance decreased as attentional load increased, but HC and SZ did not differ. Attentional load increased beta phase-locking factor at frontal, parietal, and occipital electrode sites in HC but not SZ. In SZ, however, there was a correlation between the beta attentional load effect and overall d', indicating that high-performing SZ had relatively normal beta attentional load effects. These results show that variations in attentional load are associated with beta oscillations and provide a link between attentional dysfunction and beta-generating neural circuitry in schizophrenia. PMID- 26539129 TI - Children of mentally ill parents-a pilot study of a group intervention program. AB - OBJECTIVE: The transgenerational transmission of mental disorders is one of the most prominent risk factors for the development of psychological disorders. Children of mentally ill parents are a vulnerable high risk group with overall impaired development and high rates of psychological disorders. To date there are only a few evidence based intervention programs for this group overall and hardly any in Germany. We translated the evidence based Family Talk Intervention by Beardslee (2009) and adapted it for groups. First results of this pilot study are presented. METHOD: This investigation evaluates a preventive group intervention for children of mentally ill parents. In a quasi-experimental design three groups are compared: an intervention group (Family Talk Intervention group: n = 28), a Wait Control group (n = 9), and a control group of healthy children (n = 40). Mean age of children was 10.41 years and parental disorders were mostly depressive/affective disorders (n = 30), but a small number also presented with Attention-Deficit/Hyperactivity Disorder (n = 7). RESULTS: Children of mentally ill parents showed higher rates of internalizing/externalizing disorders before and after the intervention compared to children of parents with no disorders. Post intervention children's knowledge on mental disorders was significantly enhanced in the Family Talk Intervention group compared to the Wait Control group and the healthy control group. Parental ratings of externalizing symptoms in the children were reduced to normal levels after the intervention in the Family Talk Intervention group, but not in the Wait Control group. DISCUSSION: This pilot study of a group intervention for children of mentally ill parents highlights the importance of psycho-education on parental mental disorders for children. Long term effects of children's enhanced knowledge about parental psychopathology need to be explored in future studies. PMID- 26539130 TI - Two types of potential functions and their use in the modeling of information: two applications from the social sciences. AB - In this paper we consider how two types of potential functions, the real and quantum potential can be shown to be of use in a social science context. The real potential function is a key ingredient in the Hamiltonian framework used in both classical and quantum mechanics. The quantum potential however emerges in a different way in quantum mechanics. In this paper we consider both potentials and we attempt to give them a social science interpretation within the setting of two applications. PMID- 26539131 TI - Tapping into neural resources of communication: formulaic language in aphasia therapy. PMID- 26539132 TI - Women have substantial advantage in STEM faculty hiring, except when competing against more-accomplished men. AB - Audits of tenure-track hiring reveal faculty prefer to hire female applicants over males. However, audit data do not control for applicant quality, allowing some to argue women are hired at higher rates because they are more qualified. To test this, Williams and Ceci (2015) conducted an experiment demonstrating a preference for hiring women over identically-qualified men. While their findings are consistent with audits, they raise the specter that faculty may prefer women over even more-qualified men, a claim made recently. We evaluated this claim in the present study: 158 faculty ranked two men and one woman for a tenure-track assistant professorship, and 94 faculty ranked two women and one man. In the former condition, the female applicant was slightly weaker than her two male competitors, although still strong; in the other condition the male applicant was slightly weaker than his two female competitors, although still strong. Faculty of both genders and in all fields preferred the more-qualified men over the slightly-less-qualified women, and they also preferred the stronger women over the slightly-less-qualified man. This suggests that preference for women among identically-qualified applicants found in experimental studies and in audits does not extend to women whose credentials are even slightly weaker than male counterparts. Thus these data give no support to the twin claims that weaker males are chosen over stronger females or weaker females are hired over stronger males. PMID- 26539133 TI - Knowledge, curiosity, and aesthetic chills. PMID- 26539134 TI - Principles of perceptual grouping: implications for image-guided surgery. PMID- 26539135 TI - Contingent self-esteem and vulnerability to depression: academic contingent self esteem predicts depressive symptoms in students. AB - Low self-esteem has been established as a vulnerability factor for depression. In line with recent research, we suggest that a full understanding of the role of self-esteem in depression requires consideration of contingent self-esteem as well. For most people, competence is an important source of self-esteem. Students in particular link their self-esteem to academic competence. To test the hypothesis that academic contingent self-esteem (aCSE) predicts depressive symptoms (DS), two studies were conducted. Preceding the investigation of our hypothesis, the first purpose of Study 1 was to describe the development of aCSE, self-esteem (SE) level, and DS in adolescence in a sample of German students aged 10-16 (N = 1888) in order to provide a foundation for further analyses. Then, to address the main question, age and gender differences in aCSE, SE level, and DS as well as their relations were investigated. The results show that (1) gender differences emerged after the age of 10/11. Girls scored higher on aCSE and DS and lower on SE level than did boys, and aCSE and DS decreased and SE level increased over time in boys, while the rather disadvantageous pattern in girls remained stable. (2) After controlling for SE level and aCSE, the effects of gender and age * gender interaction on DS disappeared, suggesting an influence of aCSE on DS. (3) aCSE predicted DS over and above SE level. Since the results of Study 1 did not allow for causal conclusions, a longitudinal study (N = 160) was conducted to further investigate the causal role of aCSE. According to the diathesis-stress model, aCSE was expected to serve as a diathesis for developing DS in the face of academic stress (daily hassles) during an academic semester at university. The results of Study 2 revealed that aCSE interacted with corresponding hassles to predict increases in DS. High levels of academic stress led to increases in DS only among students who strongly based their SE on academic competence. Implications for prevention and intervention of depression are discussed. PMID- 26539136 TI - Executive functioning in preschoolers with specific language impairment. AB - The pathogenesis of Specific Language Impairment (SLI) is still largely beyond our understanding. In this review, a neuropsychological perspective on language impairments in SLI is taken, focusing specifically on executive functioning (EF) in preschoolers (age range: 2.6-6.1 years) with SLI. Based on the studies described in this review, it can be concluded that similar to school-aged children with SLI, preschoolers with SLI show difficulties in working memory, inhibition and shifting, as revealed by both performance based measures and behavioral ratings. It seems plausible that a complex, reciprocal relationship exists between language and EF throughout development. Future research is needed to examine if, and if yes how, language and EF interact in SLI. Broad neuropsychological assessment in which both language and EF are taken into account may contribute to early detection of SLI. This in turn can lead to early and tailored treatment of children with (suspected) SLI aimed not only at stimulating language development but also at strengthening EF. PMID- 26539137 TI - Attentional bias in high math-anxious individuals: evidence from an emotional Stroop task. AB - Attentional bias toward threatening or emotional information is considered a cognitive marker of anxiety, and it has been described in various clinical and subclinical populations. This study used an emotional Stroop task to investigate whether math anxiety is characterized by an attentional bias toward math-related words. Two previous studies failed to observe such an effect in math-anxious individuals, although the authors acknowledged certain methodological limitations that the present study seeks to avoid. Twenty high math-anxious (HMA) and 20 low math-anxious (LMA) individuals were presented with an emotional Stroop task including math-related and neutral words. Participants in the two groups did not differ in trait anxiety or depression. We found that the HMA group showed slower response times to math-related words than to neutral words, as well as a greater attentional bias (math-related - neutral difference score) than the LMA one, which constitutes the first demonstration of an attentional bias toward math related words in HMA individuals. PMID- 26539138 TI - Comprehension and engagement in survey interviews with virtual agents. AB - This study investigates how an onscreen virtual agent's dialog capability and facial animation affect survey respondents' comprehension and engagement in "face to-face" interviews, using questions from US government surveys whose results have far-reaching impact on national policies. In the study, 73 laboratory participants were randomly assigned to respond in one of four interviewing conditions, in which the virtual agent had either high or low dialog capability (implemented through Wizard of Oz) and high or low facial animation, based on motion capture from a human interviewer. Respondents, whose faces were visible to the Wizard (and videorecorded) during the interviews, answered 12 questions about housing, employment, and purchases on the basis of fictional scenarios designed to allow measurement of comprehension accuracy, defined as the fit between responses and US government definitions. Respondents answered more accurately with the high-dialog-capability agents, requesting clarification more often particularly for ambiguous scenarios; and they generally treated the high-dialog capability interviewers more socially, looking at the interviewer more and judging high-dialog-capability agents as more personal and less distant. Greater interviewer facial animation did not affect response accuracy, but it led to more displays of engagement-acknowledgments (verbal and visual) and smiles-and to the virtual interviewer's being rated as less natural. The pattern of results suggests that a virtual agent's dialog capability and facial animation differently affect survey respondents' experience of interviews, behavioral displays, and comprehension, and thus the accuracy of their responses. The pattern of results also suggests design considerations for building survey interviewing agents, which may differ depending on the kinds of survey questions (sensitive or not) that are asked. PMID- 26539139 TI - Quantum information, cognition, and music. AB - Parallelism represents an essential aspect of human mind/brain activities. One can recognize some common features between psychological parallelism and the characteristic parallel structures that arise in quantum theory and in quantum computation. The article is devoted to a discussion of the following questions: a comparison between classical probabilistic Turing machines and quantum Turing machines.possible applications of the quantum computational semantics to cognitive problems.parallelism in music. PMID- 26539140 TI - Measuring creative imagery abilities. AB - Over the decades, creativity and imagination research developed in parallel, but they surprisingly rarely intersected. This paper introduces a new theoretical model of creative visual imagination, which bridges creativity and imagination research, as well as presents a new psychometric instrument, called the Test of Creative Imagery Abilities (TCIA), developed to measure creative imagery abilities understood in accordance with this model. Creative imagination is understood as constituted by three interrelated components: vividness (the ability to create images characterized by a high level of complexity and detail), originality (the ability to produce unique imagery), and transformativeness (the ability to control imagery). TCIA enables valid and reliable measurement of these three groups of abilities, yielding the general score of imagery abilities and at the same time making profile analysis possible. We present the results of nine studies on a total sample of more than 1700 participants, showing the factor structure of TCIA using confirmatory factor analysis, as well as provide data confirming this instrument's validity and reliability. The availability of TCIA for interested researchers may result in new insights and possibilities of integrating the fields of creativity and imagination science. PMID- 26539141 TI - Emotion has no impact on attention in a change detection flicker task. AB - Past research provides conflicting findings regarding the influence of emotion on visual attention. Early studies suggested a broadening of attentional resources in relation to positive mood. However, more recent evidence indicates that positive emotions may not have a beneficial impact on attention, and that the relationship between emotion and attention may be mitigated by factors such as task demand or stimulus valence. The current study explored the effect of emotion on attention using the change detection flicker paradigm. Participants were induced into positive, neutral, and negative mood states and then completed a change detection task. A series of neutral scenes were presented and participants had to identify the location of a disappearing item in each scene. The change was made to the center or the periphery of each scene and it was predicted that peripheral changes would be detected quicker in the positive mood condition and slower in the negative mood condition, compared to the neutral condition. In contrast to previous findings emotion had no influence on attention and whilst central changes were detected faster than peripheral changes, change blindness was not affected by mood. The findings suggest that the relationship between emotion and visual attention is influenced by the characteristics of a task, and any beneficial impact of positive emotion may be related to processing style rather than a "broadening" of attentional resources. PMID- 26539142 TI - Many faces, one rule: the role of perceptual expertise in infants' sequential rule learning. AB - Rule learning is a mechanism that allows infants to recognize and generalize rule like patterns, such as ABB or ABA. Although infants are better at learning rules from speech vs. non-speech, rule learning can be applied also to frequently experienced visual stimuli, suggesting that perceptual expertise with material to be learned is critical in enhancing rule learning abilities. Yet infants' rule learning has never been investigated using one of the most commonly experienced visual stimulus category available in infants' environment, i.e., faces. Here, we investigate 7-month-olds' ability to extract rule-like patterns from sequences composed of upright faces and compared their results to those of infants who viewed inverted faces, which presumably are encountered far less frequently than upright faces. Infants were habituated with face triads in either an ABA or ABB condition followed by a test phase with ABA and ABB triads composed of faces that differed from those showed during habituation. When upright faces were used, infants generalized the pattern presented during habituation to include the new face identities showed during testing, but when inverted faces were presented, infants failed to extract the rule. This finding supports the idea that perceptual expertise can modulate 7-month-olds' abilities to detect rule-like patterns. PMID- 26539143 TI - Child abuse predicts adult PTSD symptoms among individuals diagnosed with intellectual disabilities. AB - Prior research has shown that people with intellectual disabilities (ID) are more likely to experience child abuse as well as other forms of traumatic or negative events later in life compared to the general population. Little is known however, about the association of these experiences with adult mental health in intellectually disabled individuals. The present study aimed to assess whether child abuse in families and institutions as well as other types of adverse life events, were associated with current posttraumatic stress disorder (PTSD) and depression symptoms in individuals with ID. We conducted clinical interviews which included standardized self-report measures for childhood abuse, PTSD, and depression in an unselected sample of 56 persons with a medical diagnosis of ID who were attending a specialized welfare center. The frequency of traumatic experiences was very high, with physical and emotional child abuse being the most common trauma types. 87% of the persons reported at least one aversive experience on the family violence spectrum, and 50% of the sample reported a violent physical attack later in adulthood. 25% were diagnosed with PTSD and almost 27% had a critical score on the depression scale. Physical and emotional child abuse was positively correlated with the amount of institutional violence and the number of general traumatic events, whereas childhood sexual abuse was related to the experience of intimate partner violence in adult life. A linear regression model revealed child abuse in the family to be the only significant independent predictor of PTSD symptom severity. The current findings underscore the central role of child maltreatment in the increased risk of further victimization and in the development of mental health problems in adulthood in intellectually disabled individuals. Our data have important clinical implications and demonstrate the need for targeted prevention and intervention programs that are tailored to the specific needs of children and adults with intellectual disability. PMID- 26539144 TI - Language and other artifacts: socio-cultural dynamics of niche construction. AB - Niche construction theory is a relatively new approach in evolutionary biology that seeks to integrate an ecological dimension into the Darwinian theory of evolution by natural selection. It is regarded by many evolutionary biologists as providing a significant revision of the Neo-Darwinian modern synthesis that unified Darwin's theory of natural and sexual selection with 20th century population genetics. Niche construction theory has been invoked as a processual mediator of social cognitive evolution and of the emergence and evolution of language. I argue that language itself can be considered as a biocultural niche and evolutionary artifact. I provide both a general analysis of the cognitive and semiotic status of artifacts, and a formal analysis of language as a social and semiotic institution, based upon a distinction between the fundamental semiotic relations of "counting as" and "standing for." I explore the consequences for theories of language and language learning of viewing language as a biocultural niche. I suggest that not only do niches mediate organism-organism interactions, but also that organisms mediate niche-niche interactions in ways that affect evolutionary processes, with the evolution of human infancy and childhood as a key example. I argue that language as a social and semiotic system is not only grounded in embodied engagements with the material and social-interactional world, but also grounds a sub-class of artifacts of particular significance in the cultural history of human cognition. Symbolic cognitive artifacts materially and semiotically mediate human cognition, and are not merely informational repositories, but co-agentively constitutive of culturally and historically emergent cognitive domains. I provide examples of the constitutive cognitive role of symbolic cognitive artifacts drawn from my research with my colleagues on cultural and linguistic conceptualizations of time, and their cultural variability. I conclude by reflecting on the philosophical and social implications of understanding artifacts co-agentively. PMID- 26539145 TI - Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation. AB - What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input. PMID- 26539146 TI - Reappraisal writing relieves social anxiety and may be accompanied by changes in frontal alpha asymmetry. AB - It is widely reported that expressive writing can improve mental and physical health. However, to date, the neural correlates of expressive writing have not been reported. The current study examined the neural electrical correlates of expressive writing in a reappraisal approach. Three groups of participants were required to give a public speech. Before speaking, the reappraisal writing group was asked to write about the current stressful task in a reappraisal manner. The irrelevant writing group was asked to write about their weekly plan, and the non writing group did not write anything. It was found that following the experimental writing manipulation, both reappraisal and irrelevant writing conditions decreased self-reported anxiety levels. But when re-exposed to the stressful situation, participants in the irrelevant writing group showed increased anxiety levels, while anxiety levels remained lower in the reappraisal group. During the experimental writing manipulation period, participants in the reappraisal group had lower frontal alpha asymmetry scores than those in the irrelevant writing group. However, following re-exposure to stress, participants in the reappraisal group showed higher frontal alpha asymmetry scores than those in the irrelevant writing group. Self-reported anxiety and frontal alpha asymmetry of the non-writing condition did not change significantly across these different stages. It is noteworthy that expressive writing in a reappraisal style seems not to be a fast-acting treatment but may instead take effect in the long run. PMID- 26539147 TI - Good is up-spatial metaphors in action observation. AB - Positive objects or actions are associated with physical highness, whereas negative objects or actions are related to physical lowness. Previous research suggests that metaphorical connection ("good is up" or "bad is down") between spatial experience and evaluation of objects is grounded in actual experience with the body. Prior studies investigated effects of spatial metaphors with respect to verticality of either static objects or self-performed actions. By presenting videos of object placements, the current three experiments combined vertically-located stimuli with observation of vertically-directed actions. As expected, participants' ratings of emotionally-neutral objects were systematically influenced by the observed vertical positioning, that is, ratings were more positive for objects that were observed being placed up as compared to down. Moreover, effects were slightly more pronounced for "bad is down," because only the observed downward, but not the upward, action led to different ratings as compared to a medium-positioned action. Last, some ratings were even affected by observing only the upward/downward action, without seeing the final vertical placement of the object. Thus, both, a combination of observing a vertically directed action and seeing a vertically-located object, and observing a vertically-directed action alone, affected participants' evaluation of emotional valence of the involved object. The present findings expand the relevance of spatial metaphors to action observation, thereby giving new impetus to embodied cognition research. PMID- 26539148 TI - Does compulsive behavior in Anorexia Nervosa resemble an addiction? A qualitative investigation. AB - The characteristic relentless self-starvation behavior seen in Anorexia Nervosa (AN) has been described as evidence of compulsivity, with increasing suggestion of parallels with addictive behavior. This study used a thematic qualitative analysis to investigate the parallels between compulsive behavior in AN and Substance Use Disorders (SUD). Forty individuals currently suffering from AN completed an online questionnaire reflecting on their experience of compulsive behavior in AN. Eight main themes emerged from thematic qualitative analysis; compulsivity as central to AN, impaired control, escalating compulsions, emotional triggers, negative reactions, detrimental continuation of behavior, functional impairment, and role in recovery. These results suggested that individuals with AN view the compulsive nature of their behavior as central to the maintenance of their disorder, and as a significant barrier to recovery. The themes that emerged also showed parallels with the DSM-V criteria for SUDs, mapping onto the four groups of criteria (impaired control, social impairment, risky use of substance, pharmacological criteria). These results emphasize the need for further research to explore the possible parallels in behavioral and neural underpinnings of compulsivity in AN and SUDs, which may inform novel treatment avenues for AN. PMID- 26539149 TI - The segment-to-frame association in word reading: early effects of the interaction between segmental and suprasegmental information. AB - In four reading aloud experiments we investigated the operations occurring at the level of the phonological buffer by manipulating stress and phoneme information. In all experiments we adopted a masked priming paradigm with three-syllable Italian word targets. Experiments 1 and 2 tested the effect of pure segmental (e.g., fe%%%% - FEcola) and pure suprasegmental (CInema - FEcola) overlap, respectively. Experiments 3 and 4 tested the joint manipulation of segmental and suprasegmental information, by using prime-target pairs that shared the first syllable and did or did not share their stress pattern (e.g., FEgato - FEcola vs. feNIce - FEcola). The results showed that both segmental and suprasegmental primes affect reading at an abstract phonological level. Moreover, the joint manipulation of stress and phonemes showed an asymmetric pattern for different stress patterns, suggesting that the phonemic and the stress systems address the articulation planning through a process that starts as soon as the relevant information about the to-be-planned unit is active. PMID- 26539150 TI - The contribution of individual psychological resilience in determining the professional quality of life of Australian nurses. AB - Research Topic: The aim of this study was to determine the relative contribution of trait negative affect and individual psychological resilience in explaining the professional quality of life of nurses. MATERIALS AND METHODS: One thousand, seven hundred and forty-three Australian nurses from the public, private, and aged care sectors completed an online Qualtrics survey. The survey collected demographic data as well as measures of depression, anxiety and stress, trait negative affect, resilience, and professional quality of life. RESULTS: Significant positive relationships were observed between anxiety, depression and stress, trait negative affectivity, burnout, and secondary traumatic stress (compassion fatigue). Significant negative relationships were observed between each of the aforementioned variables and resilience and compassion satisfaction (CS). RESULTS of mediated regression analysis indicated that resilience partially mediates the relationship between trait negative affect and CS. CONCLUSION: RESULTS confirm the importance of both trait negative affect and resilience in explaining positive aspects of professional quality of life. Importantly, resilience was confirmed as a key variable impacting levels of CS and thus a potentially important variable to target in interventions aimed at improving nurse's professional quality of life. PMID- 26539151 TI - Language control is not a one-size-fits-all languages process: evidence from simultaneous interpretation students and the n-2 repetition cost. AB - Simultaneous interpretation is an impressive cognitive feat which necessitates the simultaneous use of two languages and therefore begs the question: how is language management accomplished during interpretation? One possibility is that both languages are maintained active and inhibitory control is reduced. To examine whether inhibitory control is reduced after experience with interpretation, students with varying experience were assessed on a three language switching paradigm. This paradigm provides an empirical measure of the inhibition applied to abandoned languages, the n-2 repetition cost. The groups showed different patterns of n-2 repetition costs across the three languages. These differences, however, were not connected to experience with interpretation. Instead, they may be due to other language characteristics. Specifically, the L2 n-2 repetition cost negatively correlated with self-rated oral L2 proficiency, suggesting that language proficiency may affect the use of inhibitory control. The differences seen in the L1 n-2 repetition cost, alternatively, may be due to the differing predominant interactional contexts of the groups. These results suggest that language control may be more complex than previously thought, with different mechanisms used for different languages. Further, these data represent the first use of the n-2 repetition cost as a measure to compare language control between groups. PMID- 26539152 TI - Are gifted adolescents more satisfied with their lives than their non-gifted peers? AB - Studies investigating the life satisfaction of intellectually gifted and non gifted students are scarce and often suffer from methodological shortcomings. We examined the life satisfaction of gifted and non-gifted adolescents using a rather unselected sample of N = 655 German high-school students (n = 75 gifted), adequate comparison groups of non-gifted students, and a clear definition of giftedness (general intelligence g > 2 SD above the mean). There was no difference in life satisfaction between gifted and non-gifted adolescents (d < |0.1|). Girls reported somewhat lower life satisfaction scores than boys (d = 0.24). However, this result was not specific to giftedness but was instead found across the entire sample. Thus, gifted girls were not found to be especially unsatisfied with their lives. Our findings support previous research showing that giftedness is not a risk factor for impaired psycho-social well-being of boys or girls. PMID- 26539153 TI - Corrigendum: Iconicity in the lab: a review of behavioral, developmental, and neuroimaging research into sound-symbolism. AB - [This corrects the article on p. 1246 in vol. 6, PMID: 26379581.]. PMID- 26539154 TI - Parental brain: cerebral areas activated by infant cries and faces. A comparison between different populations of parents and not. AB - Literature about parenting traditionally focused on caring behaviors and parental representations. Nowadays, an innovative line of research, interested in evaluating the neural areas and hormones implicated in the nurturing and caregiving responses, has developed. The only way to permit a newborn to survive and grow up is to respond to his needs and in order to succeed it is necessary, first of all, that the adults around him understand what his needs are. That is why adults' capacity of taking care of infants cannot disregard from some biological mechanisms, which allow them to be more responsive to the progeny and to infants in general. Many researches have proved that exist specific neural basis activating in response to infant evolutionary stimuli, such as infant cries and infant emotional facial expression. There is a sort of innate predisposition in human adults to respond to infants' signals, in order to satisfy their need and allow them to survive and become young adults capable of taking care of themselves. This article focuses on research that has investigated, in the last decade, the neural circuits underlying parental behavioral responses. Moreover, the paper compares the results of those studies that investigated the neural responses to infant stimuli under different conditions: familiar versus unknown children, parents versus non-parents and normative versus clinical samples (depression, addiction, adolescence, and PTSD). PMID- 26539156 TI - Editorial: Balloon and Stent for Ischemic and Hemorrhagic Stroke: A New Trend for Stroke Prevention and Management. PMID- 26539155 TI - Exploring Music-Based Rehabilitation for Parkinsonism through Embodied Cognitive Science. AB - Recent embodied approaches in cognitive sciences emphasize the constitutive roles of bodies and environment in driving cognitive processes. Cognition is thus seen as a distributed system based on the continuous interaction of bodies, brains, and environment. These categories, moreover, do not relate only causally, through a sequential input-output network of computations; rather, they are dynamically enfolded in each other, being mutually implemented by the concrete patterns of actions adopted by the cognitive system. However, while this claim has been widely discussed across various disciplines, its relevance and potential beneficial applications for music therapy remain largely unexplored. With this in mind, we provide here an overview of the embodied approaches to cognition, discussing their main tenets through the lenses of music therapy. In doing so, we question established methodological and theoretical paradigms and identify possible novel strategies for intervention. In particular, we refer to the music based rehabilitative protocols adopted for Parkinson's disease patients. Indeed, in this context, it has recently been observed that music therapy not only affects movement-related skills but that it also contributes to stabilizing physiological functions and improving socio-affective behaviors. We argue that these phenomena involve previously unconsidered aspects of cognition and (motor) behavior, which are rooted in the action-perception cycle characterizing the whole living system. PMID- 26539157 TI - A New Theory to Explain the Underlying Pathogenetic Mechanism of Sudden Infant Death Syndrome. AB - The author, on the basis of numerous studies on the neuropathology of SIDS, performed on a very wide set of cases, first highlights the neuronal centers of the human brainstem involved in breathing control in perinatal life, with the pontine Kolliker-Fuse nucleus (KFN) as main coordinator. What emerges from this analysis is that the prenatal respiratory movements differ from those post natally in two respects: (1) they are episodic, only aimed at the lung development and (2) they are abolished by hypoxia, not being of vital importance in utero, mainly to limit the consumption of oxygen. Then, as this fetal inhibitory reflex represents an important defense expedient, the author proposes a new original interpretation of the pathogenetic mechanism leading to SIDS. Infants, in a critical moment of the autonomic control development, in hypoxic conditions could awaken the reflex left over from fetal life and arrest breathing, as he did in similar situations in prenatal life, rather than promote the hyperventilation usually occurring to restore the normal concentration of oxygen. This behaviour obviously leads to a fatal outcome. This hypothesis is supported by immunohistochemical results showing in high percentage of SIDS victims, and not in age-matched infant controls, neurochemical alterations of the Kolliker-Fuse neurons, potentially indicative of their inactivation. The new explanation of SIDS blames a sort of auto-inhibition of the KFN functionality, wrongly arisen with the same protective purpose to preserve the life in utero, as trigger of the sudden infant death. PMID- 26539158 TI - The Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms. AB - Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. Because translational and rotational head accelerations are primary contributors to TBI from non-penetrating blunt force head trauma, the acceleration hypothesis suggests that blast-induced head accelerations may cause bTBI. The hypothesis of direct cranial transmission suggests that a pressure transient traverses the skull into the brain and directly injures brain tissue. The thoracic hypothesis of bTBI suggests that some combination of a pressure transient reaching the brain via the thorax and a vagally mediated reflex result in bTBI. These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism. PMID- 26539159 TI - The Quest to Model Chronic Traumatic Encephalopathy: A Multiple Model and Injury Paradigm Experience. AB - Chronic neurodegeneration following a history of neurotrauma is frequently associated with neuropsychiatric and cognitive symptoms. In order to enhance understanding about the underlying pathophysiology linking neurotrauma to neurodegeneration, a multi-model preclinical approach must be established to account for the different injury paradigms and pathophysiologic mechanisms. We investigated the development of tau pathology and behavioral changes using a multi-model and multi-institutional approach, comparing the preclinical results to tauopathy patterns seen in post-mortem human samples from athletes diagnosed with chronic traumatic encephalopathy (CTE). We utilized a scaled and validated blast-induced traumatic brain injury model in rats and a modified pneumatic closed-head impact model in mice. Tau hyperphosphorylation was evaluated by western blot and immunohistochemistry. Elevated-plus maze and Morris water maze were employed to measure impulsive-like behavior and cognitive deficits respectively. Animals exposed to single blast (~50 PSI reflected peak overpressure) exhibited elevated AT8 immunoreactivity in the contralateral hippocampus at 1 month compared to controls (q = 3.96, p < 0.05). Animals exposed to repeat blast (six blasts over 2 weeks) had increased AT8 (q = 8.12, p < 0.001) and AT270 (q = 4.03, p < 0.05) in the contralateral hippocampus at 1 month post injury compared to controls. In the modified controlled closed-head impact mouse model, no significant difference in AT8 was seen at 7 days, however a significant elevation was detected at 1 month following injury in the ipsilateral hippocampus compared to control (q = 4.34, p < 0.05). Elevated-plus maze data revealed that rats exposed to single blast (q = 3.53, p < 0.05) and repeat blast (q = 4.21, p < 0.05) spent more time in seconds exploring the open arms compared to controls. Morris water maze testing revealed a significant difference between groups in acquisition times on days 22-27. During the probe trial, single blast (t = 6.44, p < 0.05) and repeat blast (t = 8.00, p < 0.05) rats spent less time in seconds exploring where the platform had been located compared to controls. This study provides a multi-model example of replicating tau and behavioral changes in animals and provides a foundation for future investigation of CTE disease pathophysiology and therapeutic development. PMID- 26539160 TI - New Frontier in Glycoprotein Hormones and Their Receptors Structure-Function. AB - Last two decades of structure-function studies performed in numerous laboratories provided substantial progress in understanding basic science, physiological, pathophysiological, pharmacological, and comparative aspects of glycoprotein hormones (GPHs) and their cognate receptors. Multiple concepts and models developed based on experimental data in the past stood the test of time and have been, at least in part, confirmed and/or remained compatible with the new structures resolved at the atomic level. Major advances in understanding of the ligand-receptor relationships are heralding the dawn of a new era for GPHs and their receptors, although many basic questions still remain unanswered. This article examines retrospectively several basic science aspects of GPH super agonists and related "biosuperiors" in a broader context of the advances in the ligand-receptor structure-function relationships and new mechanistic models generated based on the structure elucidation. Due to selective focus of my comments and perspectives in certain parts, the reader is directed to the most relevant publications and reviews in the field for more comprehensive analyses. PMID- 26539162 TI - Hippocampal Functioning and Verbal Associative Memory in Adolescents with Congenital Hypothyroidism. AB - Thyroid hormone (TH) is essential for normal development of the hippocampus, which is critical for memory and particularly for learning and recalling associations between visual and verbal stimuli. Adolescents with congenital hypothyroidism (CH), who lack TH in late gestation and early life, demonstrate weak verbal recall abilities, reduced hippocampal volumes, and abnormal hippocampal functioning for visually associated material. However, it is not known if their hippocampus functions abnormally when remembering verbal associations. Our objective was to assess hippocampal functioning in CH using functional magnetic resonance imaging (fMRI). Fourteen adolescents with CH and 14 typically developing controls (TDC) were studied. Participants studied pairs of words and then, during fMRI acquisition, made two types of recognition decisions: in one they judged whether the pairs were the same as when seen originally and in the other, whether individual words were seen before regardless of pairing. Hippocampal activation was greater for pairs than items in both groups, but this difference was only significant in TDC. When we directly compared the groups, the right anterior hippocampus was the primary region in which the TDC and CH groups differed for this pair memory effect. Results signify that adolescents with CH show abnormal hippocampal functioning during verbal memory processing. PMID- 26539161 TI - A Multi-Oscillatory Circadian System Times Female Reproduction. AB - Rhythms in female reproduction are critical to insure that timing of ovulation coincides with oocyte maturation and optimal sexual arousal. This fine tuning of female reproduction involves both the estradiol feedback as an indicator of oocyte maturation, and the master circadian clock of the suprachiasmatic nuclei (SCN) as an indicator of the time of the day. Herein, we are providing an overview of the state of knowledge regarding the differential inhibitory and stimulatory effects of estradiol at different stages of the reproductive axis, and the mechanisms through which the two main neurotransmitters of the SCN, arginine vasopressin, and vasoactive intestinal peptide, convey daily time cues to the reproductive axis. In addition, we will report the most recent findings on the putative functions of peripheral clocks located throughout the reproductive axis [kisspeptin (Kp) neurons, gonadotropin-releasing hormone neurons, gonadotropic cells, the ovary, and the uterus]. This review will point to the critical position of the Kp neurons of the anteroventral periventricular nucleus, which integrate both the stimulatory estradiol signal, and the daily arginine vasopressinergic signal, while displaying a circadian clock. Finally, given the critical role of the light/dark cycle in the synchronization of female reproduction, we will discuss the impact of circadian disruptions observed during shift-work conditions on female reproductive performance and fertility in both animal model and humans. PMID- 26539164 TI - The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response. AB - Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However, different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained Stenotrophomonas maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon insertion mutant library was obtained in S. maltophilia D457. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia. PMID- 26539165 TI - Transcriptional profiling of Vibrio parahaemolyticus exsA reveals a complex activation network for type III secretion. AB - Vibrio parahaemolyticus (Vp) is a marine halophilic bacterium that is commonly associated with oysters and shrimp. Human consumption of contaminated shellfish can result in Vp mediated gastroenteritis and severe diarrheal disease. Vp encodes two type 3 secretion systems (T3SS-1 and T3SS2) that have been functionally implicated in cytotoxicity and enterotoxicity respectively. In this study, we profiled protein secretion and temporal promoter activities associated with exsA and exsB gene expression. exsA is an AraC-like transcriptional activator that is critical for activating multiple operons that encode T3SS-1 genes, whereas exsB is thought to encode an outer membrane pilotin component for T3SS-1. The exsBA genetic locus has two predicted promoter elements. The predicted exsB and exsA promoters were individually cloned upstream of luxCDABE genes in reporter plasmid constructs allowing for in situ, real-time quantitative light emission measurements under many growth conditions. Low calcium growth conditions supported maximal exsB and exsA promoter activation. exsB promoter activity exhibited high basal activity and resulted in an exsBA co-transcript. Furthermore, a separate proximal exsA promoter showed initial low basal activity yet eventually exceeded that of exsB and reached maximal levels after 2.5 h corresponding to an entry into early log phase. exsA promoter activity was significantly higher at 30 degrees C than 37 degrees C, which also coincided with increased secretion levels of specific T3SS-1 effector proteins. Lastly, bioinformatic analyses identified a putative expanded ExsA binding motif for multiple transcriptional operons. These findings suggest a two wave model of Vp T3SS-I induction that integrates two distinct promoter elements and environmental signals into a complex ExsA activation framework. PMID- 26539163 TI - Bioengineering Beige Adipose Tissue Therapeutics. AB - Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and their potential for the metabolic therapies. PMID- 26539166 TI - Diversity and distribution of Actinobacteria associated with reef coral Porites lutea. AB - Actinobacteria is a ubiquitous major group in coral holobiont. The diversity and spatial and temporal distribution of actinobacteria have been rarely documented. In this study, diversity of actinobacteria associated with mucus, tissue and skeleton of Porites lutea and in the surrounding seawater were examined every 3 months for 1 year on Luhuitou fringing reef. The population structures of the P. lutea-associated actinobacteria were analyzed using phylogenetic analysis of 16S rRNA gene clone libraries, which demonstrated highly diverse actinobacteria profiles in P. lutea. A total of 25 described families and 10 unnamed families were determined in the populations, and 12 genera were firstly detected in corals. The Actinobacteria diversity was significantly different between the P. lutea and the surrounding seawater. Only 10 OTUs were shared by the seawater and coral samples. Redundancy and hierarchical cluster analyses were performed to analyze the correlation between the variations of actinobacteria population within the divergent compartments of P. lutea, seasonal changes, and environmental factors. The actinobacteria communities in the same coral compartment tended to cluster together. Even so, an extremely small fraction of OTUs was common in all three P. lutea compartments. Analysis of the relationship between actinobacteria assemblages and the environmental parameters showed that several genera were closely related to specific environmental factors. This study highlights that coral-associated actinobacteria populations are highly diverse, and spatially structured within P. lutea, and they are distinct from which in the ambient seawater. PMID- 26539169 TI - Discovery of novel small molecule modulators of Clavibacter michiganensis subsp. michiganensis. AB - Clavibacter michiganensis subsp. michiganensis (Cmm) is a Gram-positive seed transmitted bacterial phytopathogen responsible for substantial economic losses by adversely affecting tomato production worldwide. A high-throughput, cell-based screen was adapted to identify novel small molecule growth inhibitors to serve as leads for future bactericide development. A library of 4,182 compounds known to be bioactive against Saccharomyces cerevisiae was selected for primary screening against Cmm wild-type strain C290 for whole-cell growth inhibition. Four hundred sixty-eight molecules (11.2% hit rate) were identified as bacteriocidal or bacteriostatic against Cmm at 200 MUM. Seventy-seven candidates were selected based on Golden Triangle analyses for secondary screening. Secondary screens showed that several of these candidates were strain-selective. Several compounds were inhibitory to multiple Cmm strains as well as Bacillus subtilis, but not to Pseudomonas fluorescens, Mitsuaria sp., Lysobacter enzymogenes, Lactobacillus rhamnosus, Bifidobacterium animalis, or Escherichia coli. Most of the compounds were not phytotoxic and did not show overt host toxicity. Using a novel 96-well bioluminescent Cmm seedling infection assay, we assessed effects of selected compounds on pathogen infection. The 12 most potent novel molecules were identified by compiling the scores from all secondary screens combined with the reduction of pathogen infection in planta. When tested for ability to develop resistance to the top-12 compounds, no resistant Cmm were recovered, suggesting that the discovered compounds are unlikely to induce resistance. In conclusion, here we report top-12 compounds that provide chemical scaffolds for future Cmm specific bactericide development. PMID- 26539168 TI - The out-of-the-delta hypothesis: dense human populations in low-lying river deltas served as agents for the evolution of a deadly pathogen. AB - Cholera is a diarrheal disease that has changed the history of mankind, devastating the world with seven pandemics from 1817 to the present day. Although there is little doubt in the causative agent of these pandemics being Vibrio cholerae of the O1 serogroup, where, when, and how this pathogen emerged is not well understood. V. cholerae is a ubiquitous coastal species that likely existed for tens of thousands of years. However, the evolution of a strain capable of causing a large-scale epidemic is likely more recent historically. Here, we propose that the unique human and physical geography of low-lying river deltas made it possible for an environmental bacterium to evolve into a deadly human pathogen. Such areas are often densely populated and salt intrusion in drinking water frequent. As V. cholerae is most abundant in brackish water, its favored environment, it is likely that coastal inhabitants would regularly ingest the bacterium and release it back in the environment. This creates a continuous selection pressure for V. cholerae to adapt to life in the human gut. PMID- 26539167 TI - Impact of cocaine abuse on HIV pathogenesis. AB - Over 1.2 million people in the United States are infected with the human immunodeficiency virus type 1 (HIV-1). Tremendous progress has been made over the past three decades on many fronts in the prevention and treatment of HIV-1 disease. However, HIV-1 infection is incurable and antiretroviral drugs continue to remain the only effective treatment option for HIV infected patients. Unfortunately, only three out of ten HIV-1 infected individuals in the US have the virus under control. Thus, majority of HIV-1 infected individuals in the US are either unaware of their infection status or not connected/retained to care or are non-adherent to antiretroviral therapy (ART). This national public health crisis, as well as the ongoing global HIV/AIDS pandemic, is further exacerbated by substance abuse, which serves as a powerful cofactor at every stage of HIV/AIDS including transmission, diagnosis, pathogenesis, and treatment. Clinical studies indicate that substance abuse may increase viral load, accelerate disease progression and worsen AIDS-related mortality even among ART-adherent patients. However, confirming a direct causal link between substance abuse and HIV/AIDS in human patients remains a highly challenging endeavor. In this review we will discuss the recent and past developments in clinical and basic science research on the effects of cocaine abuse on HIV-1 pathogenesis. PMID- 26539171 TI - Retraction: In silico 3D structure analysis accelerates the solution of a real viral structure and antibodies docking mechanism. AB - [This retracts the article on p. 387 in vol. 3, PMID: 23133439.]. PMID- 26539172 TI - Interactions of Dnd proteins involved in bacterial DNA phosphorothioate modification. AB - DNA phosphorothioation (PT) is the first discovered physiological DNA backbone modification, in which a non-bridging oxygen atom of the phosphodiester bond is replaced with a sulfur atom in Rp (rectus for plane) configuration. PT modification is governed by a highly conserved gene cluster dndA/iscS-dndBCDE that is widespread across bacterial and archaeal species. However, little is known about how these proteins coordinately react with each other to perform oxygen-sulfur swap. We here demonstrated that IscS, DndC, DndD and DndE form a protein complex of which the molecular ratio for four proteins in the complex is approximate 1:1:1:1. DndB here displayed little or weak affinity to the complex and the constructs harboring dndACDE can confer the host in vivo PT modification. Using co-purification and pull down strategy, we demonstrated that the four proteins assemble into a pipeline in collinear to its gene organization, namely, IscS binding to DndC, DndC binding to DndD, and DndD binding to DndE. Moreover, weak interactions between DndE and IscS, DndE and DndC were also identified. PMID- 26539173 TI - Upscale of recombinant alpha-L-rhamnosidase production by Pichia pastoris Mut(S) strain. AB - Pichia pastoris is currently one of the most preferred microorganisms for recombinant enzyme production due to its efficient expression system. The advantages include the production of high amounts of recombinant proteins containing the appropriate posttranslational modifications and easy cultivation conditions. alpha-L-Rhamnosidase is a biotechnologically important enzyme in food and pharmaceutical industry, used for example in debittering of citrus fruit juices, rhamnose pruning from naringin, or enhancement of wine aromas, creating a demand for the production of an active and stable enzyme. The production of recombinant alpha-L-rhamnosidase cloned in the Mut(S) strain of P. pastoris KM71H was optimized. The encoding gene is located under the control of the AOX promoter, which is induced by methanol whose concentration is instrumental for these strain types. Fermentation was upscaled in bioreactors employing various media and several methanol-feeding strategies. It was found that fed batch with BSM media was more effective compared to BMMH (Buffered Methanol-complex Medium) media due to lower cost and improved biomass formation. In BSM (Basal Salt Medium) medium, the dry cell weight reached approximately 60 g/L, while in BMMH it was only 8.3 g/L, without additional glycerol, which positively influenced the amount of enzyme produced. New methanol feeding strategy, based on the level of dissolved oxygen was developed in this study. This protocol that is entirely independent on methanol monitoring was up scaled to a 19.5-L fermenter with 10-L working volume with the productivity of 13.34 mgprot/L/h and specific activity of alpha-L-rhamnosidase of 82 U/mg. The simplified fermentation protocol was developed for easy and effective fermentation of P. pastoris Mut(S) based on dissolved oxygen monitoring in the induction phase of an enzyme production. PMID- 26539170 TI - Extracellular vesicles from infected cells: potential for direct pathogenesis. AB - Infections that result in natural or manmade spread of lethal biological agents are a concern and require national and focused preparedness. In this manuscript, as part of an early diagnostics and pathogen treatment strategy, we have focused on extracellular vesicles (EVs) that arise following infections. Although the field of biodefense does not currently have a rich resource in EVs literature, none the less, similar pathogens belonging to the more classical emerging and non emerging diseases have been studied in their EV/exosomal contents and function. These exosomes are formed in late endosomes and released from the cell membrane in almost every cell type in vivo. These vesicles contain proteins, RNA, and lipids from the cells they originate from and function in development, signal transduction, cell survival, and transfer of infectious material. The current review focuses on how different forms of infection exploit the exosomal pathway and how exosomes can be exploited artificially to treat infection and disease and potentially also be used as a source of vaccine. Virally-infected cells can secrete viral as well as cellular proteins and RNA in exosomes, allowing viruses to cause latent infection and spread of miRNA to nearby cells prior to a subsequent infection. In addition to virally-infected host cells, bacteria, protozoa, and fungi can all release small vesicles that contain pathogen associated molecular patterns, regulating the neighboring uninfected cells. Examples of exosomes from both virally and bacterially infected cells point toward a re-programming network of pathways in the recipient cells. Finally, many of these exosomes contain cytokines and miRNAs that in turn can effect gene expression in the recipient cells through the classical toll-like receptor and NFkappaB pathway. Therefore, although exosomes do not replicate as an independent entity, they however facilitate movement of infectious material through tissues and may be the cause of many pathologies seen in infected hosts. PMID- 26539174 TI - Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues. AB - Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA) or "coral tumors" are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB) were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch's postulates in efforts to understand the etiology and progression of SGA. PMID- 26539175 TI - The evolution of early cellular systems viewed through the lens of biological interactions. AB - The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimized or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are "free living." As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favor refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem), a distributed genome (a system resulting from an evolutionary transition involving more than one cell) and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution. PMID- 26539176 TI - Wide distribution of carbapenem resistant Acinetobacter baumannii in burns patients in Iran. AB - Antimicrobial resistance in carbapenem non-susceptible Acinetobacter baumannii (CNSAb) is a major public health concern globally. This study determined the antibiotic resistance and molecular epidemiology of CNSAb isolates from a referral burn center in Tehran, Iran. Sixty-nine CNSAb isolates were tested for susceptibility to antimicrobial agents using the E test methodology. Multiple locus variable number tandem repeat analysis (MLVA), Multilocus sequence typing (MLST) and multiplex PCR were performed. PCR assays tested for ambler classes A, B, and D beta-lactamases. Detection of ISAba1, characterization of integrons, and biofilm formation were investigated. Fifty-three (77%) isolates revealed XDR phenotypes. High prevalence of bla OXA-23-like (88%) and bla PER-1 (54%) were detected. ISAba1 was detected upstream of bla ADC, bla OXA-23-like and bla OXA51 like genes in, 97, 42, and 26% of isolates, respectively. Thirty-one (45%) isolates were assigned to international clone (IC) variants. MLVA identified 56 distinct types with six clusters and 53 singleton genotypes. Forty previously known MLST sequence types forming 5 clonal complexes were identified. The Class 1 integron (class 1 integrons) gene was identified in 84% of the isolates. The most prevalent (33%) cassette combination was aacA4-catB8-aadA1. The IC variants were predominant in the A. baumannii lineage with the ability to form strong biofilms. The XDR-CNSAb from burned patients in Iran is resistant to various antimicrobials, including tigecycline. This study shows wide genetic diversity in CNSAb. Integrating the new Iranian A. baumannii IC variants into the epidemiologic clonal and susceptibility profile databases can help effective global control measures against the XDR-CNSAb pandemic. PMID- 26539177 TI - Interspecies interactions are an integral determinant of microbial community dynamics. AB - This study investigated the factors that determine the dynamics of bacterial communities in a complex system using multidisciplinary methods. Since natural and engineered microbial ecosystems are too complex to study, six types of synthetic microbial ecosystems (SMEs) were constructed under chemostat conditions with phenol as the sole carbon and energy source. Two to four phenol-degrading, phylogenetically and physiologically different bacterial strains were used in each SME. Phylogeny was based on the nucleotide sequence of 16S rRNA genes, while physiologic traits were based on kinetic and growth parameters on phenol. Two indices, J parameter and "interspecies interaction," were compared to predict which strain would become dominant in an SME. The J parameter was calculated from kinetic and growth parameters. On the other hand, "interspecies interaction," a new index proposed in this study, was evaluated by measuring the specific growth activity, which was determined on the basis of relative growth of a strain with or without the supernatant prepared from other bacterial cultures. Population densities of strains used in SMEs were enumerated by real-time quantitative PCR (qPCR) targeting the gene encoding the large subunit of phenol hydroxylase and were compared to predictions made from J parameter and interspecies interaction calculations. In 4 of 6 SEMs tested the final dominant strain shown by real-time qPCR analyses coincided with the strain predicted by both the J parameter and the interspecies interaction. However, in SMEII-2 and SMEII-3 the final dominant Variovorax strains coincided with prediction of the interspecies interaction but not the J parameter. These results demonstrate that the effects of interspecies interactions within microbial communities contribute to determining the dynamics of the microbial ecosystem. PMID- 26539178 TI - Responses of soil microeukaryotic communities to short-term fumigation-incubation revealed by MiSeq amplicon sequencing. AB - In soil microbiology, there is a "paradox" of soil organic carbon (SOC) mineralization, which is that even though chloroform fumigation destroys majority of the soil microbial biomass, SOC mineralization continues at the same rate as in the non-fumigated soil during the incubation period. Soil microeukaryotes as important SOC decomposers, however, their community-level responses to chloroform fumigation are not well understood. Using the 18S rRNA gene amplicon sequencing, we analyzed the composition, diversity, and C-metabolic functions of a grassland soil and an arable soil microeukaryotic community in response to fumigation followed by a 30-day incubation. The grassland and arable soil microeukaryotic communities were dominated by the fungal Ascomycota (80.5-93.1% of the fungal sequences), followed by the protistan Cercozoa and Apicomplexa. In the arable soil fungal community, the predominance of the class Sordariomycetes was replaced by the class Eurotiomycetes after fumigation at days 7 and 30 of the incubation. Fumigation changed the microeukaryotic alpha-diversity in the grassland soil at days 0 and 7, and beta-diversity in the arable soil at days 7 and 30. Network analysis indicated that after fumigation fungi were important groups closely related to other taxa. Most phylotypes (especially Sordariomycetes, Dothideomycetes, Coccidia, and uncultured Chytridiomycota) were inhibited, and only a few were positively stimulated by fumigation. Despite the inhibited Sordariomycetes, the fumigated communities mainly consisted of Eurotiomycetes and Sordariomycetes (21.9 and 36.5% relative frequency, respectively), which are able to produce hydrolytic enzymes associated with SOC mineralization. Our study suggests that fumigation not only decreases biomass size, but modulates the composition and diversity of the soil microeukaryotic communities, which are capable of driving SOC mineralization by release of hydrolytic enzymes during short-term fumigation-incubation. PMID- 26539179 TI - Modification of photosynthetic electron transport and amino acid levels by overexpression of a circadian-related histidine kinase hik8 in Synechocystis sp. PCC 6803. AB - Cyanobacteria perform oxygenic photosynthesis, and the maintenance of photosynthetic electron transport chains is indispensable to their survival in various environmental conditions. Photosynthetic electron transport in cyanobacteria can be studied through genetic analysis because of the natural competence of cyanobacteria. We here show that a strain overexpressing hik8, a histidine kinase gene related to the circadian clock, exhibits an altered photosynthetic electron transport chain in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Respiratory activity was down-regulated under nitrogen-replete conditions. Photosynthetic activity was slightly lower in the hik8-overexpressing strain than in the wild-type after nitrogen depletion, and the values of photosynthetic parameters were altered by hik8 overexpression under nitrogen-replete and nitrogen-depleted conditions. Transcripts of genes encoding Photosystem I and II were increased by hik8 overexpression under nitrogen-replete conditions. Nitrogen starvation triggers increase in amino acids but the magnitude of the increase in several amino acids was diminished by hik8 overexpression. These genetic data indicate that Hik8 regulates the photosynthetic electron transport, which in turn alters primary metabolism during nitrogen starvation in this cyanobacterium. PMID- 26539180 TI - Membrane homeoviscous adaptation in the piezo-hyperthermophilic archaeon Thermococcus barophilus. AB - The archaeon Thermococcus barophilus, one of the most extreme members of hyperthermophilic piezophiles known thus far, is able to grow at temperatures up to 103 degrees C and pressures up to 80 MPa. We analyzed the membrane lipids of T. barophilus by high performance liquid chromatography-mass spectrometry as a function of pressure and temperature. In contrast to previous reports, we show that under optimal growth conditions (40 MPa, 85 degrees C) the membrane spanning tetraether lipid GDGT-0 (sometimes called caldarchaeol) is a major membrane lipid of T. barophilus together with archaeol. Increasing pressure and decreasing temperature lead to an increase of the proportion of archaeol. Reversely, a higher proportion of GDGT-0 is observed under low pressure and high temperature conditions. Noticeably, pressure and temperature fluctuations also impact the level of unsaturation of apolar lipids having an irregular polyisoprenoid carbon skeleton (unsaturated lycopane derivatives), suggesting a structural role for these neutral lipids in the membrane of T. barophilus. Whether these apolar lipids insert in the membrane or not remains to be addressed. However, our results raise questions about the structure of the membrane in this archaeon and other Archaea harboring a mixture of di- and tetraether lipids. PMID- 26539182 TI - Mitigation of efflorescence of wallboard by means of bio-mineralization. AB - Cement-based material is one of the most versatile and largest amounts of building materials which can not only be used in load-bearing structure but also be used as decoration materials, like brick, wallboard, and tile. However, white calcium carbonate always be found on the surface of wallboard. This phenomenon is generally called efflorescence, which has no damage to wallboard, but has aesthetic impact. In this research, Bacillus mucilaginosus was pre-added to the cement matrix to reduce the efflorescence of wallboard. Image processing, thermogravimetric analysis and permeability test were used to characterize the efflorescence degree of wallboard. The results showed that the bacterium captured atmospheric CO2 by carbonic anhydrase and promoted the CO2to react with Ca(OH)2. This process not only reduced the content of Ca(OH)2 but also improved the compactness of wallboard. In addition, the maximal decrease of efflorescence area of wallboard was gotten when the content of microbial was up to 4% of the mass of cementitious material and the proportion of efflorescence area reduced from 32 +/ 3 to 5 +/- 1% of the whole area of surface layer. At the same time, the values of compressive and flexural strength were the highest and the surface layer of wallboard was the most compact. The observed reduction of efflorescence was indeed due to the effect of bio-mineralization. This promising method was noted to be cheap, convenient, environment friendly, and which has the potential in various practical applications. PMID- 26539181 TI - T-cell activation or tolerization: the Yin and Yang of bacterial superantigens. AB - Bacterial superantigens (SAg) are exotoxins from pathogens which interact with innate and adaptive immune cells. The paradox that SAgs cause activation and inactivation/anergy of T-cells was soon recognized. The structural and molecular events following SAg binding to antigen presenting cells (APCs) followed by crosslinking of T-cell receptors were characterized in detail. Activation, cytokine burst and T-cell anergy have been described in vitro and in vivo. Later it became clear that SAg-induced T-cell anergy is in part caused by SAg-dependent activation of T-regulatory cells (Tregs). Although the main focus of analyses was laid on T-cells, it was also shown that SAg binding to MHC class II molecules on APCs induces a signal, which leads to activation and secretion of pro inflammatory cytokines. Accordingly APCs are mandatory for T-cell activation. So far it is not known, whether APCs play a role during SAg-triggered activation of Tregs. We therefore tested whether in SAg (Streptococcal pyrogenic exotoxin A) treated APCs an anti-inflammatory program is triggered in addition. We show here that not only the anti-inflammatory cytokine IL-10 and the co-inhibitory surface molecule PD-L1 (CD274) but also inhibitory effector systems like indoleamine 2,3 dioxygenase (IDO) or intracellular negative feedback loops (suppressor of cytokine signaling molecules, SOCS) are induced by SAgs. Moreover, cyclosporine A completely prevented induction of this program. We therefore propose that APCs triggered by SAgs play a key role in T-cell activation as well as inactivation and induction of Treg cells. PMID- 26539183 TI - An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products. AB - Finger millet is an ancient African cereal crop, domesticated 7000 years ago in Ethiopia, reaching India at 3000 BC. Finger millet is reported to be resistant to various fungal pathogens including Fusarium sp. We hypothesized that finger millet may host beneficial endophytes (plant-colonizing microbes) that contribute to the antifungal activity. Here we report the first isolation of endophyte(s) from finger millet. Five distinct fungal species were isolated from roots and predicted taxonomically based on 18S rDNA sequencing. Extracts from three putative endophytes inhibited growth of F. graminearum and three other pathogenic Fusarium species. The most potent anti-Fusarium strain (WF4, predicted to be a Phoma sp.) was confirmed to behave as an endophyte using pathogenicity and confocal microscopy experiments. Bioassay-guided fractionation of the WF4 extract identified four anti-fungal compounds, viridicatol, tenuazonic acid, alternariol, and alternariol monomethyl ether. All the purified compounds caused dramatic breakage of F. graminearum hyphae in vitro. These compounds have not previously been reported to have anti-Fusarium activity. None of the compounds, except for tenuazonic acid, have previously been reported to be produced by Phoma. We conclude that the ancient, disease-tolerant crop, finger millet, is a novel source of endophytic anti-fungal natural products. This paper suggests the value of the crops grown by subsistence farmers as sources of endophytes and their natural products. Application of these natural chemicals to solve real world problems will require further validation. PMID- 26539184 TI - Phylogenetic diversity of culturable fungi in the Heshang Cave, central China. AB - Caves are nutrient-limited and dark subterranean ecosystems. To date, attention has been focused on geological research of caves in China, whilst indigenous microbial diversity has been insufficiently characterized. Here, we report the fungal diversity in the pristine, oligotrophic, karst Heshang Cave, central China, using a culture-dependent method coupled with the analysis of the fungal rRNA-ITS gene sequences. A total of 194 isolates were obtained with six different media from 14 sampling sites of sediments, weathered rocks, and bat guanos. Phylogenetic analysis clustered the 194 sequenced isolates into 33 genera within 15 orders of three phyla, Ascomycota, Basidiomycota, and Zygomycota, indicating a high degree of fungal diversity in the Heshang Cave. Notably, 16 out of the 36 fungal genera were also frequently observed in solution caves around the world and 23 genera were previously found in carbonate cave, indicating potential similarities among fungal communities in cave ecosystems. However, 10 genera in this study were not reported previously in any solution caves, thus expanding our knowledge about fungal diversity in cave ecosystems. Moreover, culturable fungal diversity varied from one habitat to another within the cave, being the highest in sediments, followed by weathered rocks and bat guanos as indicated by alpha diversity indexes. At the genus level, Penicillium accounted for 40, 54, and 52% in three habitats of sediments, weathered rocks, and bat guanos, respectively. Trichoderma, Paecilomyces, and Aspergillus accounted for 9, 22, and 37% in the above habitats, correspondingly. Despite of the dominance of Penicillium in all samples, beta-diversity index indicated significant differences between each two fungal communities in the three habitats in view of both the composition and abundance. Our study is the first report on fungal communities in a natural pristine solution cave system in central China and sheds light on fungal diversity and functions in cave ecosystems. PMID- 26539185 TI - An assessment on DNA microarray and sequence-based methods for the characterization of methicillin-susceptible Staphylococcus aureus from Nigeria. AB - Staphylococcus aureus is an important human pathogen causing nosocomial and community-acquired infections worldwide. In the characterization of this opportunistic pathogen, DNA microarray hybridization technique is used as an alternative to sequence based genotyping to obtain a comprehensive assessment on the virulence, resistance determinants, and population structure. The objective of this study was to characterize a defined collection of S. aureus isolates from Nigeria using the microarray technique, and to assess the extent that it correlates with sequence-based genotyping methods. The clonal diversity and genomic content of 52 methicillin-susceptible Staphylococcus aureus (MSSA) were investigated by spa typing, MLST and DNA microarray hybridization. More than half (55.8%) of these isolates were associated with clonal complexes (CCs) typically associated with methicillin-resistant S. aureus (MRSA) clones i.e., CC1, CC5, CC8, CC30, and CC45. Certain genes linked with virulence (hlgA and clfA) and adherence (ebpS, fnbA, sspA, sspB, and sspP) were detected in all isolates. A number of genes or gene clusters were associated with distinct clonal types. The enterotoxin gene cluster (egc) was linked with CC5, CC25, CC30, CC45, and CC121, enterotoxin H gene (seh) with CC1, exfoliative toxin D gene (etd) with CC25 and CC80, and the epidermal cell differentiation inhibitor B gene (edinB) with CC25, CC80, and CC152. The excellent agreement between data from DNA microarray and MLST in the delineation of Nigerian MSSA isolates indicates that the microarray technique is a useful tool to provide information on antibiotic resistance, clonal diversity and virulence factors associated with infection and disease. PMID- 26539186 TI - Sequential parametric optimization of methane production from different sources of forest raw material. AB - The increase in environmental problems and the shortage of fossil fuels have led to the need for action in the development of sustainable and renewable fuels. Methane is produced through anaerobic digestion of organic materials and is a biofuel with very promising characteristics. The success in using methane as a biofuel has resulted in the operation of several commercial-scale plants and the need to exploit novel materials to be used. Forest biomass can serve as an excellent candidate for use as raw material for anaerobic digestion. During this work, both hardwood and softwood species-which are representative of the forests of Sweden-were used for the production of methane. Initially, when untreated forest materials were used for the anaerobic digestion, the yields obtained were very low, even with the addition of enzymes, reaching a maximum of only 40 mL CH4/g VS when birch was used. When hydrothermal pretreatment was applied, the enzymatic digestibility improved up to 6.7 times relative to that without pretreatment, and the yield of methane reached up to 254 mL CH4/g VS. Then the effect of chemical/enzymatic detoxification was examined, where laccase treatment improved the methane yield from the more harshly pretreated materials while it had no effect on the more mildly pretreated material. Finally, addition of cellulolytic enzymes during the digestion improved the methane yields from spruce and pine, whereas for birch separate saccharification was more beneficial. To achieve high yields in spruce 30 filter paper units (FPU)/g was necessary, whereas 15 FPU/g was enough when pine and birch were used. During this work, the highest methane yields obtained from pine and birch were 179.9 mL CH4/g VS and 304.8 mL CH4/g VS, respectively. For mildly and severely pretreated spruce, the methane yields reached 259.4 mL CH4/g VS and 276.3 mL CH4/g VS, respectively. We have shown that forest material can serve as raw material for efficient production of methane. The initially low yields from the untreated materials were significantly improved by the introduction of a hydrothermal pretreatment. Moreover, enzymatic detoxification was beneficial, but mainly for severely pretreated materials. Finally, enzymatic saccharification increased the methane yields even further. PMID- 26539187 TI - Heterologous xylose isomerase pathway and evolutionary engineering improve xylose utilization in Saccharomyces cerevisiae. AB - Xylose utilization is one key issue for the bioconversion of lignocelluloses. It is a promising approach to engineering heterologous pathway for xylose utilization in Saccharomyces cerevisiae. Here, we constructed a xylose-fermenting yeast SyBE001 through combinatorial fine-tuning the expression of XylA and endogenous XKS1. Additional overexpression of genes RKI1, RPE1, TKL1, and TAL1 in the non-oxidative pentose phosphate pathway (PPP) in SyBE001 increased the xylose consumption rate by 1.19-fold. By repetitive adaptation, the xylose utilization rate was further increased by ~10-fold in the resultant strain SyBE003. Gene expression analysis identified a variety of genes with significantly changed expression in the PPP, glycolysis and the tricarboxylic acid cycle in SyBE003. PMID- 26539188 TI - Molecular characterization of forest soil based Paenibacillus elgii and optimization of various culture conditions for its improved antimicrobial activity. AB - Microorganisms have provided a bounty of bioactive secondary metabolites with very exciting biological activities such as antibacterial, antifungal antiviral, and anticancer, etc. The present study aims at the optimization of culture conditions for improved antimicrobial production of Paenibacillus elgii obtained from Wayanad forest of Western Ghats region of Kerala, India. A bacterial strain isolated from the Western Ghats forest soil of Wayanad, Kerala, India was identified as P. elgii by 16S rRNA gene sequencing. P. elgii recorded significant board spectrum activity against all human and plant pathogenic microorganism tested except Candida albicans. It has been well known that even minor variations in the fermentation medium may impact not only the quantity of desired bioactive metabolites but also the general metabolic profile of the producing microorganisms. Thus, further studies were carried out to assess the impact of medium components on the antimicrobial production of P. elgii and to optimize an ideal fermentation medium to maximize its antimicrobial production. Out of three media [nutrient broth (NA), Luria broth (LB) and Trypticase soy broth (TSB)] used for fermentation, TSB medium recorded significant activity. Glucose and meat peptone were identified as the best carbon and nitrogen sources, which significantly affected the antibiotic production when supplemented with TSB medium. Next the effect of various fermentation conditions such as temperature, pH, and incubation time on the production of antimicrobial compounds was studied on TSB + glucose + meat peptone and an initial pH of 7 and a temperature of 30 degrees C for 3 days were found to be optimum for maximum antimicrobial production. The results indicate that medium composition in the fermentation media along with cultural parameters plays a vital role in the enhanced production of antimicrobial substances. PMID- 26539189 TI - Anthropogenic impact on diazotrophic diversity in the mangrove rhizosphere revealed by nifH pyrosequencing. AB - Diazotrophs in the mangrove rhizosphere play a major role in providing new nitrogen to the mangrove ecosystem and their composition and activity are strongly influenced by anthropogenic activity and ecological conditions. In this study, the diversity of the diazotroph communities in the rhizosphere sediment of five tropical mangrove sites with different levels of pollution along the north and south coastline of Singapore were studied by pyrosequencing of the nifH gene. Bioinformatics analysis revealed that in all the studied locations, the diazotroph communities comprised mainly of members of the diazotrophic cluster I and cluster III. The detected cluster III diazotrophs, which were composed entirely of sulfate-reducing bacteria, were more abundant in the less polluted locations. The metabolic capacities of these diazotrophs indicate the potential for bioremediation and resiliency of the ecosystem to anthropogenic impact. In heavily polluted locations, the diazotrophic community structures were markedly different and the diversity of species was significantly reduced when compared with those in a pristine location. This, together with the increased abundance of Marinobacterium, which is a bioindicator of pollution, suggests that anthropogenic activity has a negative impact on the genetic diversity of diazotrophs in the mangrove rhizosphere. PMID- 26539190 TI - Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence. AB - Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed. PMID- 26539191 TI - CD8(+)CD122(+) T-Cells: A Newly Emerging Regulator with Central Memory Cell Phenotypes. AB - CD8(+)CD122(+) T-cells have been traditionally described as antigen-specific memory T-cells that respond to previously encountered antigens more quickly and vigorously than their naive counterparts. However, mounting evidence has demonstrated that murine CD8(+)CD122(+) T-cells exhibit a central memory phenotype (CD44(high)CD62L(high)), regulate T cell homeostasis, and act as regulatory T-cells (Treg) by suppressing both autoimmune and alloimmune responses. Importantly, naturally occurring murine CD8(+)CD122(+) Tregs are more potent in immunosuppression than their CD4(+)CD25(+) counterparts. They appear to be acting in an antigen-non-specific manner. Human CD8(+)CXCR3(+) T-cells are the equivalent of murine CD8(+)CD122(+) Tregs and also exhibit central memory phenotypes. In this mini-review article, we will summarize recent progresses in their phenotypes, homeostatic expansion, antigen-specificity, roles in the suppression of alloimmune and autoimmune responses, and the mechanisms underlying their inhibitory function. PMID- 26539192 TI - Oral Vaccination of Fish - Antigen Preparations, Uptake, and Immune Induction. AB - The oral route offers the most attractive approach of immunization of fish for a number of reasons: the ease of administration of antigens, it is less stressful than parenteral delivery and in principle, it is applicable to small and large sized fish; it also provides a procedure for oral boosting during grow-out periods in cages or ponds. There are, however, not many commercial vaccines available at the moment due to lack of efficacy and challenges associated with production of large quantities of antigens. These are required to stimulate an effective immune response locally and systemically, and need to be protected against degradation before they reach the sites where immune induction occurs. The hostile stomach environment is believed to be particularly important with regard to degradation of antigens in certain species. There is also a poor understanding about the requirements for proper immune induction following oral administration on one side, and the potential for induction of tolerance on the other. To what extent primary immunization via the oral route will elicit both local and systemic responses is not understood in detail. Furthermore, to what extent parenteral delivery will protect mucosal/gut surfaces and vice-versa is also not fully understood. We review the work that has been done on the subject and discuss it in light of recent advances that include mass production of antigens, including the use of plant systems. Different encapsulation techniques that have been developed in the quest to protect antigens against digestive degradation, as well as to target them for appropriate immune induction are also highlighted. PMID- 26539193 TI - Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation. AB - Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental. PMID- 26539194 TI - Integrins are Mechanosensors That Modulate Human Eosinophil Activation. AB - Eosinophil migration to the lung is primarily regulated by the eosinophil selective family of eotaxin chemokines, which mobilize intracellular calcium (Ca(2+)) and orchestrate myriad changes in cell structure and function. Eosinophil function is also known to be flow-dependent, although the molecular cognate of this mechanical response has yet to be adequately characterized. Using confocal fluorescence microscopy, we determined the effects of fluid shear stress on intracellular calcium concentration ([Ca(2+)]i) in human peripheral blood eosinophils by perfusing cells in a parallel-plate flow chamber. Our results indicate that fluid perfusion evokes a calcium response that leads to cell flattening, increase in cell area, shape change, and non-directional migration. None of these changes are seen in the absence of a flow stimulus, and all are blocked by chelation of intracellular Ca(2+) using BAPTA. These changes are enhanced by stimulating the cells with eotaxin-1. The perfusion-induced calcium response (PICR) could be blocked by pre-treating cells with selective (CDP-323) and non-selective (RGD tripeptides) integrin receptor antagonists, suggesting that alpha4beta7/alpha4beta1 integrins mediate this response. Overall, our study provides the first pharmacological description of a molecular mechanosensor that may collaborate with the eotaxin-1 signaling program in order to control human eosinophil activation. PMID- 26539195 TI - Gene Expression Profiling of Human Monocyte-derived Dendritic Cells - Searching for Molecular Regulators of Tolerogenicity. AB - The ability of dendritic cells (DCs) to initiate and modulate antigen-specific immune responses has made them attractive targets for immunotherapy. Since DC research in humans is limited by the scarcity of DC populations in the blood circulation, most of our knowledge about DC biology and function has been obtained in vitro from monocyte-derived DCs (moDCs), which can be readily generated in sufficient numbers and are able to differentiate into distinct functional subsets depending on the nature of stimulus. In particular, moDCs with tolerogenic properties (tolDCs) possess great therapeutic potential for the treatment of autoimmune diseases. Several protocols have been developed to generate tolDCs in vitro, able to reinstruct auto-reactive T cells and to promote regulatory cells. While ligands and soluble mediators, by which DCs shape immune responses, have been vastly studied, the intracellular pathways and transcriptional regulators that govern tolDC differentiation and function are poorly understood. Whole-genome microarrays and proteomics provide useful strategies to dissect the complex molecular processes that promote tolerogenicity. Only few attempts have been made to understand tolDC biology through a global view on "omics" profiles. So far, the identification of a common regulator of tolerogenicity has been hampered by the fact that each protocol, used for tolDC generation, targets distinct signaling pathways. Here, we review the progress in understanding the transcriptional regulation of moDC differentiation, with a special focus on tolDCs, and highlight candidate molecules that might be associated with DC tolerogenicity. PMID- 26539196 TI - Transcriptional Regulation of Mononuclear Phagocyte Development. AB - Mononuclear phagocytes (MP) are a quite unique subset of hematopoietic cells, which comprise dendritic cells (DC), monocytes as well as monocyte-derived and tissue-resident macrophages. These cells are extremely diverse with regard to their origin, their phenotype as well as their function. Developmentally, DC and monocytes are constantly replenished from a bone marrow hematopoietic progenitor. The ontogeny of macrophages is more complex and is temporally linked and specified by the organ where they reside, occurring early during embryonic or perinatal life. The functional heterogeneity of MPs is certainly a consequence of the tissue of residence and also reflects the diverse ontogeny of the subsets. In this review, we will highlight the developmental pathways of murine MP, with a particular emphasis on the transcriptional factors that regulate their development and function. Finally, we will discuss and point out open questions in the field. PMID- 26539198 TI - Pre-fractionation strategies to resolve pea (Pisum sativum) sub-proteomes. AB - Legumes are important crop plants and pea (Pisum sativum L.) has been investigated as a model with respect to several physiological aspects. The sequencing of the pea genome has not been completed. Therefore, proteomic approaches are currently limited. Nevertheless, the increasing numbers of available EST-databases as well as the high homology of the pea and medicago genome (Medicago truncatula Gaertner) allow the successful identification of proteins. Due to the un-sequenced pea genome, pre-fractionation approaches have been used in pea proteomic surveys in the past. Aside from a number of selective proteome studies on crude extracts and the chloroplast, few studies have targeted other components such as the pea secretome, an important sub-proteome of interest due to its role in abiotic and biotic stress processes. The secretome itself can be further divided into different sub-proteomes (plasma membrane, apoplast, cell wall proteins). Cell fractionation in combination with different gel electrophoresis, chromatography methods and protein identification by mass spectrometry are important partners to gain insight into pea sub-proteomes, post translational modifications and protein functions. Overall, pea proteomics needs to link numerous existing physiological and biochemical data to gain further insight into adaptation processes, which play important roles in field applications. Future developments and directions in pea proteomics are discussed. PMID- 26539197 TI - Role of Dendritic Cells in the Induction of Lymphocyte Tolerance. AB - The ability of dendritic cells (DCs) to trigger tolerance or immunity is dictated by the context in which an antigen is encountered. A large body of evidence indicates that antigen presentation by steady-state DCs induces peripheral tolerance through mechanisms such as the secretion of soluble factors, the clonal deletion of autoreactive T cells, and feedback control of regulatory T cells. Moreover, recent understandings on the function of DC lineages and the advent of murine models of DC depletion have highlighted the contribution of DCs to lymphocyte tolerance. Importantly, these findings are now being applied to human research in the contexts of autoimmune diseases, allergies, and transplant rejection. Indeed, DC-based immunotherapy research has made important progress in the area of human health, particularly in regards to cancer. A better understanding of several DC-related aspects including the features of DC lineages, milieu composition, specific expression of surface molecules, the control of signaling responses, and the identification of competent stimuli able to trigger and sustain a tolerogenic outcome will contribute to the success of DC based immunotherapy in the area of lymphocyte tolerance. This review will discuss the latest advances in the biology of DC subtypes related to the induction of regulatory T cells, in addition to presenting current ex vivo protocols for tolerogenic DC production. Particular attention will be given to the molecules and signals relevant for achieving an adequate tolerogenic response for the treatment of human pathologies. PMID- 26539199 TI - Transcriptome analysis of wheat inoculated with Fusarium graminearum. AB - Plants are frequently exposed to microorganisms like fungi, bacteria, and viruses that cause biotic stresses. Fusarium head blight (FHB) is an economically risky wheat disease, which occurs upon Fusarium graminearum (Fg) infection. Moderately susceptible (cv. "Mizrak 98") and susceptible (cv. "Gun 91") winter type bread wheat cultivars were subjected to transcriptional profiling after exposure to Fg infection. To examine the early response to the pathogen in wheat, we measured gene expression alterations in mock and pathogen inoculated root crown of moderately susceptible (MS) and susceptible cultivars at 12 hours after inoculation (hai) using 12X135K microarray chip. The transcriptome analyses revealed that out of 39,179 transcripts, 3668 genes in microarray were significantly regulated at least in one time comparison. The majority of differentially regulated transcripts were associated with disease response and the gene expression mechanism. When the cultivars were compared, a number of transcripts and expression alterations varied within the cultivars. Especially membrane related transcripts were detected as differentially expressed. Moreover, diverse transcription factors showed significant fold change values among the cultivars. This study presented new insights to understand the early response of selected cultivars to the Fg at 12 hai. Through the KEGG analysis, we observed that the most altered transcripts were associated with starch and sucrose metabolism and gluconeogenesis pathways. PMID- 26539200 TI - Roles of membrane trafficking in plant cell wall dynamics. AB - The cell wall is one of the characteristic components of plant cells. The cell wall composition differs among cell types and is modified in response to various environmental conditions. To properly generate and modify the cell wall, many proteins are transported to the plasma membrane or extracellular space through membrane trafficking, which is one of the key protein transport mechanisms in eukaryotic cells. Given the diverse composition and functions of the cell wall in plants, the transport of the cell wall components and proteins that are involved in cell wall-related events could be specialized for each cell type, i.e., the machinery for cell wall biogenesis, modification, and maintenance could be transported via different trafficking pathways. In this review, we summarize the recent progress in the current understanding of the roles and mechanisms of membrane trafficking in plant cells and focus on the biogenesis and regulation of the cell wall. PMID- 26539201 TI - Beyond ectomycorrhizal bipartite networks: projected networks demonstrate contrasted patterns between early- and late-successional plants in Corsica. AB - The ectomycorrhizal (ECM) symbiosis connects mutualistic plants and fungal species into bipartite networks. While links between one focal ECM plant and its fungal symbionts have been widely documented, systemic views of ECM networks are lacking, in particular, concerning the ability of fungal species to mediate indirect ecological interactions between ECM plant species (projected-ECM networks). We assembled a large dataset of plant-fungi associations at the species level and at the scale of Corsica using molecular data and unambiguously host-assigned records to: (i) examine the correlation between the number of fungal symbionts of a plant species and the average specialization of these fungal species, (ii) explore the structure of the plant-plant projected network and (iii) compare plant association patterns in regard to their position along the ecological succession. Our analysis reveals no trade-off between specialization of plants and specialization of their partners and a saturation of the plant projected network. Moreover, there is a significantly lower-than expected sharing of partners between early- and late-successional plant species, with fewer fungal partners for early-successional ones and similar average specialization of symbionts of early- and late-successional plants. Our work paves the way for ecological readings of Mediterranean landscapes that include the astonishing diversity of below-ground interactions. PMID- 26539202 TI - Extreme low temperature tolerance in woody plants. AB - Woody plants in boreal to arctic environments and high mountains survive prolonged exposure to temperatures below -40 degrees C and minimum temperatures below -60 degrees C, and laboratory tests show that many of these species can also survive immersion in liquid nitrogen at -196 degrees C. Studies of biochemical changes that occur during acclimation, including recent proteomic and metabolomic studies, have identified changes in carbohydrate and compatible solute concentrations, membrane lipid composition, and proteins, notably dehydrins, that may have important roles in survival at extreme low temperature (ELT). Consideration of the biophysical mechanisms of membrane stress and strain lead to the following hypotheses for cellular and molecular mechanisms of survival at ELT: (1) Changes in lipid composition stabilize membranes at temperatures above the lipid phase transition temperature (-20 to -30 degrees C), preventing phase changes that result in irreversible injury. (2) High concentrations of oligosaccharides promote vitrification or high viscosity in the cytoplasm in freeze-dehydrated cells, which would prevent deleterious interactions between membranes. (3) Dehydrins bind membranes and further promote vitrification or act stearically to prevent membrane-membrane interactions. PMID- 26539203 TI - High temperature and vapor pressure deficit aggravate architectural effects but ameliorate non-architectural effects of salinity on dry mass production of tomato. AB - Tomato (Solanum lycopersicum L.) is an important vegetable crop and often cultivated in regions exposed to salinity and high temperatures (HT) which change plant architecture, decrease canopy light interception and disturb physiological functions. However, the long-term effects of salinity and HT combination (S+HT) on plant growth are still unclear. A dynamic functional-structural plant model (FSPM) of tomato was parameterized and evaluated for different levels of S+HT combinations. The evaluated model was used to quantify the contributions of morphological changes (architectural effects) and physiological disturbances (non architectural effects) on the reduction of shoot dry mass under S+HT. The model predicted architectural variables with high accuracy (>85%), which ensured the reliability of the model analyses. HT enhanced architectural effects but reduced non-architectural effects of salinity on dry mass production. The stronger architectural effects of salinity under HT could not be counterbalanced by the smaller non-architectural effects. Therefore, long-term influences of HT on shoot dry mass under salinity were negative at the whole plant level. Our model analysis highlights the importance of plant architecture at canopy level in studying the plant responses to the environments and shows the merits of dynamic FSPMs as heuristic tools. PMID- 26539205 TI - Low Temperature-Induced 30 (LTI30) positively regulates drought stress resistance in Arabidopsis: effect on abscisic acid sensitivity and hydrogen peroxide accumulation. AB - As a dehydrin belonging to group II late embryogenesis abundant protein (LEA) family, Arabidopsis Low Temperature-Induced 30 (LTI30)/XERO2 has been shown to be involved in plant freezing stress resistance. However, the other roles of AtLTI30 remain unknown. In this study, we found that the expression of AtLTI30 was largely induced by drought stress and abscisic acid (ABA) treatments. Thereafter, AtLTI30 knockout mutants and overexpressing plants were isolated to investigate the possible involvement of AtLTI30 in ABA and drought stress responses. AtLTI30 knockout mutants were less sensitive to ABA-mediated seed germination, while AtLTI30 overexpressing plants were more sensitive to ABA compared with wild type (WT). Consistently, the AtLTI30 knockout mutants displayed decreased drought stress resistance, while the AtLTI30 overexpressing plants showed improved drought stress resistance compared with WT, as evidenced by a higher survival rate and lower leaf water loss than WT after drought stress. Moreover, manipulation of AtLTI30 expression positively regulated the activities of catalases (CATs) and endogenous proline content, as a result, negatively regulated drought stress-triggered hydrogen peroxide (H2O2) accumulation. All these results indicate that AtLTI30 is a positive regulator of plant drought stress resistance, partially through the modulation of ABA sensitivity, H2O2 and proline accumulation. PMID- 26539206 TI - Draft genome sequence of Oryza sativa elite indica cultivar RP Bio-226. PMID- 26539204 TI - Insights into molecular and metabolic events associated with fruit response to post-harvest fungal pathogens. AB - Due to post-harvest losses more than 30% of harvested fruits will not reach the consumers' plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by post-harvest fungal pathogens during fruit ripening. PMID- 26539207 TI - Genotype by environment interaction and breeding for robustness in livestock. AB - The increasing size of the human population is projected to result in an increase in meat consumption. However, at the same time, the dominant position of meat as the center of meals is on the decline. Modern objections to the consumption of meat include public concerns with animal welfare in livestock production systems. Animal breeding practices have become part of the debate since it became recognized that animals in a population that have been selected for high production efficiency are more at risk for behavioral, physiological and immunological problems. As a solution, animal breeding practices need to include selection for robustness traits, which can be implemented through the use of reaction norms analysis, or though the direct inclusion of robustness traits in the breeding objective and in the selection index. This review gives an overview of genotype * environment interactions (the influence of the environment, reaction norms, phenotypic plasticity, canalization, and genetic homeostasis), reaction norms analysis in livestock production, options for selection for increased levels of production and against environmental sensitivity, and direct inclusion of robustness traits in the selection index. Ethical considerations of breeding for improved animal welfare are discussed. The discussion on animal breeding practices has been initiated and is very alive today. This positive trend is part of the sustainable food production movement that aims at feeding 9.15 billion people not just in the near future but also beyond. PMID- 26539208 TI - A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability. AB - Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red-green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies. PMID- 26539209 TI - dcVar: a method for identifying common variants that modulate differential correlation structures in gene expression data. AB - Recent studies have implicated the role of differential co-expression or correlation structure in gene expression data to help explain phenotypic differences. However, few attempts have been made to characterize the function of variants based on their role in regulating differential co-expression. Here, we describe a statistical methodology that identifies pairs of transcripts that display differential correlation structure conditioned on genotypes of variants that regulate co-expression. Additionally, we present a user-friendly, computationally efficient tool, dcVar, that can be applied to expression quantitative trait loci (eQTL) or RNA-Seq datasets to infer differential co expression variants (dcVars). We apply dcVar to the HapMap3 eQTL dataset and demonstrate the utility of this methodology at uncovering novel function of variants of interest with examples from a height genome-wide association and cancer drug resistance. We provide evidence that differential correlation structure is a valuable intermediate molecular phenotype for further characterizing the function of variants identified in GWAS and related studies. PMID- 26539211 TI - A loopy view of telomere evolution. AB - About a decade ago, I proposed that t-loops, the lariat structures adopted by many eukaryotic telomeres, could explain how the transition from circular to linear chromosomes was successfully negotiated by early eukaryotes. Here I reconsider this loopy hypothesis in the context of the idea that eukaryotes evolved through a period of genome invasion by Group II introns. PMID- 26539210 TI - Prospects and challenges for the conservation of farm animal genomic resources, 2015-2025. AB - Livestock conservation practice is changing rapidly in light of policy developments, climate change and diversifying market demands. The last decade has seen a step change in technology and analytical approaches available to define, manage and conserve Farm Animal Genomic Resources (FAnGR). However, these rapid changes pose challenges for FAnGR conservation in terms of technological continuity, analytical capacity and integrative methodologies needed to fully exploit new, multidimensional data. The final conference of the ESF Genomic Resources program aimed to address these interdisciplinary problems in an attempt to contribute to the agenda for research and policy development directions during the coming decade. By 2020, according to the Convention on Biodiversity's Aichi Target 13, signatories should ensure that "...the genetic diversity of ...farmed and domesticated animals and of wild relatives ...is maintained, and strategies have been developed and implemented for minimizing genetic erosion and safeguarding their genetic diversity." However, the real extent of genetic erosion is very difficult to measure using current data. Therefore, this challenging target demands better coverage, understanding and utilization of genomic and environmental data, the development of optimized ways to integrate these data with social and other sciences and policy analysis to enable more flexible, evidence-based models to underpin FAnGR conservation. At the conference, we attempted to identify the most important problems for effective livestock genomic resource conservation during the next decade. Twenty priority questions were identified that could be broadly categorized into challenges related to methodology, analytical approaches, data management and conservation. It should be acknowledged here that while the focus of our meeting was predominantly around genetics, genomics and animal science, many of the practical challenges facing conservation of genomic resources are societal in origin and are predicated on the value (e.g., socio-economic and cultural) of these resources to farmers, rural communities and society as a whole. The overall conclusion is that despite the fact that the livestock sector has been relatively well-organized in the application of genetic methodologies to date, there is still a large gap between the current state-of-the-art in the use of tools to characterize genomic resources and its application to many non-commercial and local breeds, hampering the consistent utilization of genetic and genomic data as indicators of genetic erosion and diversity. The livestock genomic sector therefore needs to make a concerted effort in the coming decade to enable to the democratization of the powerful tools that are now at its disposal, and to ensure that they are applied in the context of breed conservation as well as development. PMID- 26539212 TI - Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines. AB - BACKGROUND: Phospholipases A2 (PLA2s) are abundant components of snake venoms that have been extensively studied due to their pharmacological and pathophysiological effects on living organisms. This study aimed to assess the antitumor potential of BthTX-I, a basic myotoxic PLA2 isolated from Bothrops jararacussu venom, by evaluating in vitro processes of cytotoxicity, modulation of the cell cycle and induction of apoptosis in human (HL-60 and HepG2) and murine (PC-12 and B16F10) tumor cell lines. METHODS: The cytotoxic effects of BthTX-I were evaluated on the tumor cell lines HL-60 (promyelocytic leukemia), HepG2 (human hepatocellular carcinoma), PC-12 (murine pheochromocytoma) and B16F10 (murine melanoma) using the MTT method. Flow cytometry technique was used for the analysis of cell cycle alterations and death mechanisms (apoptosis and/or necrosis) induced in tumor cells after treatment with BthTX-I. RESULTS: It was observed that BthTX-I was cytotoxic to all evaluated tumor cell lines, reducing their viability in 40 to 50 %. The myotoxin showed modulating effects on the cell cycle of PC-12 and B16F10 cells, promoting delay in the G0/G1 phase. Additionally, flow cytometry analysis indicated cell death mainly by apoptosis. B16F10 was more susceptible to the effects of BthTX-I, with ~40 % of the cells analyzed in apoptosis, followed by HepG2 (~35 %), PC-12 (~25 %) and HL-60 (~4 %). CONCLUSIONS: These results suggest that BthTX-I presents antitumor properties that may be useful for developing new therapeutic strategies against cancer. PMID- 26539213 TI - P300 and Decision Making under Risk and Ambiguity. AB - Our study aims to contrast the neural temporal features of early stage of decision making in the context of risk and ambiguity. In monetary gambles under ambiguous or risky conditions, 12 participants were asked to make a decision to bet or not, with the event-related potentials (ERPs) recorded meantime. The proportion of choosing to bet in ambiguous condition was significantly lower than that in risky condition. An ERP component identified as P300 was found. The P300 amplitude elicited in risky condition was significantly larger than that in ambiguous condition. The lower bet rate in ambiguous condition and the smaller P300 amplitude elicited by ambiguous stimuli revealed that people showed much more aversion in the ambiguous condition than in the risky condition. The ERP results may suggest that decision making under ambiguity occupies higher working memory and recalls more past experience while decision making under risk mainly mobilizes attentional resources to calculate current information. These findings extended the current understanding of underlying mechanism for early assessment stage of decision making and explored the difference between the decision making under risk and ambiguity. PMID- 26539214 TI - Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis. AB - Diffuse splanchnic venous thrombosis (DSVT), formerly defined as contraindication for liver transplantation (LT), is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x) and renoportal anastomosis (1x). Median follow-up was 58 months (range: 0,5 to 130 months). Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental) portal hypertension. PMID- 26539215 TI - Similarity Evaluation of Different Origins and Species of Dendrobiums by GC-MS and FTIR Analysis of Polysaccharides. AB - GC-MS method combined with FTIR techniques by the analysis of polysaccharide was applied to evaluate the similarity between wild (W) and tissue-cultured (TC) Dendrobium huoshanense (DHS), Dendrobium officinale (DO), and Dendrobium moniliforme (DM) as well as 3 wild Dendrobium spp.: Dendrobium henanense (DHN), Dendrobium loddigesii (DL), and Dendrobium crepidatum (DC). Eight monosaccharides involving xylose, arabinose, rhamnose, glucose, mannose, fructose, galactose, and galacturonic acid were identified in the polysaccharide from each Dendrobium sample while the contents of the monosugars varied remarkably across origins and species. Further similarity evaluation based on GC-MS data showed that the r cor values of different origins of DHS, DO, and DM were 0.831, 0.865, and 0.884, respectively, while the r cor values ranged from 0.475 to 0.837 across species. FTIR files of the polysaccharides revealed that the similarity coefficients between W and TC-DHS, DO, and DM were 88.7%, 86.8%, and 88.5%, respectively, in contrast to the similarity coefficients varying from 57.4% to 82.6% across species. These results suggested that the structures of polysaccharides between different origins of the investigated Dendrobiums might be higher than what we had supposed. PMID- 26539216 TI - Cellular Nutrition in Complex Three-Dimensional Scaffolds: A Comparison between Experiments and Computer Simulations. AB - Studies on bone cell ingrowth into synthetic, porous three-dimensional (3D) implants showed difficulties arising from impaired cellular proliferation and differentiation in the core region of these scaffolds with increasing scaffold volume in vitro. Therefore, we developed an in vitro perfusion cell culture module, which allows the analysis of cells in the interior of scaffolds under different medium flow rates. For each flow rate the cell viability was measured and compared with results from computer simulations that predict the local oxygen supply and shear stress inside the scaffold based on the finite element method. We found that the local cell viability correlates with the local oxygen concentration and the local shear stress. On the one hand the oxygen supply of the cells in the core becomes optimal with a higher perfusion flow. On the other hand shear stress caused by high flow rates impedes cell vitality, especially at the surface of the scaffold. Our results demonstrate that both parameters must be considered to derive an optimal nutrient flow rate. PMID- 26539217 TI - Panax notoginseng Saponins Attenuate Phenotype Switching of Vascular Smooth Muscle Cells Induced by Notch3 Silencing. AB - Panax notoginseng saponins (PNS) could maintain vascular smooth muscle cells (VSMCs) in stable phenotypes so as to keep blood vessel elasticity as well as prevent failing in endovascular treatment with stent. Downregulation of Notch3 expression in VSMCs could influence the phenotype of VSMCs under pathologic status. However, whether PNS is able to attenuate the Notch3 silencing induced phenotype switching of VSMCs remains poorly understood. Primary human VSMCs were transfected with a plasmid containing a small interfering RNA (siRNA) against Notch3 and then exposed to different doses of PNS. The control groups included cells not receiving any treatment and cells transfected with a control siRNA. Phenotypic switching was evaluated by observing cell morphology with confocal microscopy, as well as examining alpha-SM-actin, SM22alpha, and OPN using Western blot. Downregulated Notch3 with a siRNA induced apparent phenotype switching, as reflected by morphologic changes, decreased expression of alpha-SM-actin and SM22alpha and increased expression of OPN. These changes were inhibited by PNS in a dose-dependent manner. The phenotype switching of VSMCs induced by Notch3 knockdown could be inhibited by PNS in a dose-dependent manner. Our study provided new evidence for searching effective drug for amending stability of atherosclerotic disease. PMID- 26539218 TI - Anxiety and Anger Symptoms in Hwabyung Patients Improved More following 4 Weeks of the Emotional Freedom Technique Program Compared to the Progressive Muscle Relaxation Program: A Randomized Controlled Trial. AB - Background. The Emotional Freedom Technique (EFT) is a meridian-based psychological therapy. The present clinical trial investigates the effectiveness of EFT as a new treatment option for Hwabyung (HB) patients experiencing anger and compares the efficacy to the Progressive Muscle Relaxation (PMR), the conventional meditation technique. Methods. The EFT and progressive muscle relaxation (PMR) methods were performed on 27 HB patients, and their capacities to alleviate anxiety, anger, and emotional status were compared. After a 4-week program, a survey was conducted; patients then completed a self-training program for 4 weeks, followed by a second survey. Results. During the initial 4 weeks, the EFT group experienced a significant decrease in the HB symptom scale, anger state, and paranoia ideation (p < 0.05). Over the entire 9-week interval, there were significant decreases in the HB symptom scale, anxiety state, anger state, anger trait, somatization, anxiety, hostility, and so on in EFT group (p < 0.05). Conclusion. The EFT group showed improved psychological symptoms and physical symptoms greater than those observed in the PMR group. EFT more effectively alleviated HB symptoms compared to PMR. EFT group showed better maintenance during self-training, suggesting good model of self-control treatment in HB patients. PMID- 26539219 TI - Comparison of the Spasmolytic Effects of Jakyak-Gamcho Decoctions Derived via Different Extractants. AB - Aim. To investigate whether differences in the amounts of effective index components in Jakyak-Gamcho decoctions derived via extraction with either water or ethanol were associated with differential spasmolytic effectiveness. Methods. The amounts of effective index components (paeoniflorin, benzoic acid, glycyrrhizin, and isoliquiritin) contained in water-extracted Jakyak-Gamcho decoction and 70% ethanol-extracted Jakyak-Gamcho decoction were compared by high performance liquid chromatography. Muscle cramp reduction rates were compared between the two decoctions by comparing the degrees of muscle contraction, measured as the tension developed during electrical stimulation, before and 1 and 2 h after injection in rats. Results. The relative amounts of effective index components were, on average, about 43% higher in the 70% ethanol-extracted decoction than in the water-extracted decoction. Two hours after injection, 0.25 g/kg of 70% ethanol-extracted decoction produced a significantly greater spasmolytic effect than 0.25 g/kg of water-extracted Jakyak-Gamcho decoction or distilled water (both p < 0.05). Conclusion. Differences in the amounts of effective index components resulting from the use of different extractants were associated with differences in spasmolytic effectiveness. Hence, it may be worthwhile to investigate alternative extraction methods in terms of extraction efficiency and in vivo effectiveness for various herbal medicines in the future. PMID- 26539220 TI - The Clinical Relevance of Serum NDKA, NMDA, PARK7, and UFDP Levels with Phlegm Heat Syndrome and Treatment Efficacy Evaluation of Traditional Chinese Medicine in Acute Ischemic Stroke. AB - According to the methods of Patient-Reported Outcome (PRO) based on the patient reports internationally and referring to U.S. Food and Drug Administration (FDA) guide, some scholars developed this PRO of stroke which is consistent with China's national conditions, and using it the feel of stroke patients was introduced into the clinical efficacy evaluation system of stoke. "Ischemic Stroke TCM Syndrome Factor Diagnostic Scale (ISTSFDS)" and "Ischemic Stroke TCM Syndrome Factor Evaluation Scale (ISTSFES)" were by "Major State Basic Research Development Program of China (973 Program) (number 2003CB517102)." ISTSFDS can help to classify and diagnose the CM syndrome reasonably and objectively with application of syndrome factors. Six syndrome factors, internal-wind syndrome, internal-fire syndrome, phlegm-dampness syndrome, blood-stasis syndrome, qi deficiency syndrome, and yin-deficiency syndrome, were included in ISTSFDS and ISTSFES. TCM syndrome factor was considered to be present if the score was greater than or equal to 10 according to ISTSFDS. In our study, patients with phlegm-heat syndrome were recruited, who met the diagnosis of both "phlegm dampness" and "internal-fire" according to ISTSFDS. ISTSFES was used to assess the syndrome severity; in our study it was used to assess the severity of phlegm heat syndrome (phlegm-heat syndrome scores = phlegm-dampness syndrome scores + internal-fire syndrome scores). PMID- 26539221 TI - An Overview of Meta-Analyses of Danhong Injection for Unstable Angina. AB - Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved. PMID- 26539222 TI - Enhanced Protective Effect of the Combination of Uncaria and Semen Raphani on Vascular Endothelium in Spontaneously Hypertensive Rats. AB - Endothelial dysfunction and low-grade inflammation are closely associated with hypertension and other cardiovascular diseases. The combination of Uncaria (U) and Semen Raphani (R) is common in traditional Chinese medicine for the treatment of hypertension and heart diseases. We aimed to investigate the therapeutic effect of the combination of Uncaria and Semen Raphani on spontaneously hypertensive rats (SHRs), and valsartan was used as a positive control. In the present study, all extracts decreased systolic pressure, diastolic pressure, and mean arterial pressure. U alone showed antihypertensive efficacy and effectively decreased CECs count, while R alone showed efficacy in relieving inflammatory level. The combination of U and R showed enhanced effectiveness at lowering activated CECs and improving endothelial integrity of thoracic aorta and mesenteric artery and normalized the level of plasma biomarkers of endothelial damage. The combination of U and R decreased the mRNA level of VCAM-1, Sel-L, TFPI, and Sel-P, while it elevated mRNA expression of FGF-1 and THBD of the thoracic aorta, which may be, at least in part, involved in the mechanism of protective effect on hypertensive endothelial injury. PMID- 26539223 TI - Intercultural Usage of Mori Folium: Comparison Review from a Korean Medical Perspective. AB - Objectives. A review on studies related to the use of Mori folium, the leaves of Morus alba, was conducted with the goal of identifying new clinical applications in Korean medicine. Methods. Global literature search was conducted using three electronic databases up to January 2015 with the term Morus alba and its Korean terms. KM literatures including textbooks and standard pharmacopoeia were separately hand-searched and reviewed to provide comparison. Data were extracted according to predetermined criteria, and clinical uses were standardized with ICD 10 categories. Results. 159 potentially relevant studies were identified, and 18 articles including 12 ethnopharmacologic and 6 clinical studies were finally included in this analysis. Ethnopharmacologic studies from 8 countries provided 17 clinical uses. We found that five out of six clinical trials were related to diabetes and suggested a moderate short-term to mild long-term effect. And 43 Korean texts also provided 156 clinical uses in 35 categories including ocular and respiratory disorders. Discussion and Conclusions. Though majority of the clinical uses were also found in Korean medicine literature, treatment of infertility, jaundice, cognitive disorder, and hyperpigmentation was found to be effective and diabetes with Morus alba was recognized to have clinical importance. PMID- 26539224 TI - Spatial Patterns of the Indications of Acupoints Using Data Mining in Classic Medical Text: A Possible Visualization of the Meridian System. AB - The indications of acupoints are thought to be highly associated with the lines of the meridian systems. The present study used data mining methods to analyze the characteristics of the indications of each acupoint and to visualize the relationships between the acupoints and disease sites in the classic Korean medical text Chimgoogyeongheombang. Using a term frequency-inverse document frequency (tf-idf) scheme, the present study extracted valuable data regarding the indications of each acupoint according to the frequency of the cooccurrences of eight Source points and eighteen disease sites. Furthermore, the spatial patterns of the indications of each acupoint on a body map were visualized according to the tf-idf values. Each acupoint along the different meridians exhibited different constellation patterns at various disease sites. Additionally, the spatial patterns of the indications of each acupoint were highly associated with the route of the corresponding meridian. The present findings demonstrate that the indications of each acupoint were primarily associated with the corresponding meridian system. Furthermore, these findings suggest that the routes of the meridians may have clinical implications in terms of identifying the constellations of the indications of acupoints. PMID- 26539225 TI - Effects of Chung-Pae Inhalation Therapy on a Mouse Model of Chronic Obstructive Pulmonary Disease. AB - Chung-pae (CP) inhalation therapy is a method frequently used in Korea to treat lung disease, especially chronic obstructive pulmonary disease (COPD). This study investigated the effects of CP inhalation on a COPD animal model. C57BL/6 mice received porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) alternately three times for 3 weeks to induce COPD. Then, CP (5 or 20 mg/kg) was administered every 2 h after the final LPS administration. The effect of CP was evaluated by bronchoalveolar lavage (BAL) fluid analysis, histological analysis of lung tissue, and reverse transcription polymerase chain reaction analysis of mRNA of interleukin- (IL-) 1beta, tumor necrosis factor- (TNF-) alpha, IL-6, and tumor growth factor- (TGF-) beta. Intratracheal CP administration reduced the number of leukocytes and neutrophils in BAL fluid, inhibited the histological appearance of lung damage, and decreased the mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, and TGF-beta. Intratracheal CP administration effectively decreased the chronic inflammation and pathological changes in a PPE- and LPS-induced COPD mouse model. Therefore, we suggest that CP is a promising strategy for COPD. PMID- 26539226 TI - Protective Effect of Artemisia asiatica Extract and Its Active Compound Eupatilin against Cisplatin-Induced Renal Damage. AB - The present study investigated the renoprotective effect of an Artemisia asiatica extract and eupatilin in kidney epithelial (LLC-PK1) cells. Although cisplatin is effective against several cancers, its use is limited due to severe nephrotoxicity. Eupatilin is a flavonoid compound isolated from the Artemisia plant and possesses antioxidant as well as potent anticancer properties. In the LLC-PK1 cellular model, the decline in cell viability induced by oxidative stress, such as that induced by cisplatin, was significantly and dose-dependently inhibited by the A. asiatica extract and eupatilin. The increased protein expressions of phosphorylated JNK and p38 by cisplatin in cells were markedly reduced after A. asiatica extract or eupatilin cotreatment. The elevated expression of cleaved caspase-3 was significantly reduced by A. asiatica extract and eupatilin, and the elevated percentage of apoptotic cells after cisplatin treatment in LLC-PK1 cells was markedly decreased by cotreatment with A. asiatica extract or eupatilin. Taken together, these results suggest that A. asiatica extract and eupatilin could cure or prevent cisplatin-induced renal toxicity without any adverse effect; thus, it can be used in combination with cisplatin to prevent nephrotoxicity. PMID- 26539227 TI - Resistance to Antibiotics and Antifungal Medicinal Products: Can Complementary and Alternative Medicine Help Solve the Problem in Common Infection Diseases? The Introduction of a Dutch Research Consortium. AB - The increase of antibiotic resistance worldwide, rising numbers of deaths and costs associated with this, and the fact that hardly any new antimicrobial drugs have been developed during the last decade have increased the interest in Complementary and Alternative Medicine (CAM) therapeutic interventions, if proven safe and effective. Observational studies on clinical CAM practices demonstrate positive effects of treatment of infections with CAM therapies (clinical effects, patient satisfaction) in combination with small percentages of antibiotics prescription. However, Cochrane reviews and other studies demonstrate that in most instances the quality of clinical trials on CAM treatment of infections is currently too low to provide sufficient evidence. Therefore a Dutch consortium on (in vitro and clinical) scientific research on CAM and antibiotic resistance has been formed. The aim and objective of the consortium is to establish an enduring partnership and to develop expertise to further develop and investigate safe and effective CAM treatments for infectious diseases of humans (and animals). A first ongoing project on the development of safe and effective biobased CAM antimycotics in women with (recurrent) vaginal candidiasis infection is introduced. PMID- 26539228 TI - Tang-Tong-Fang Confers Protection against Experimental Diabetic Peripheral Neuropathy by Reducing Inflammation. AB - Tang-tong-fang (TTF) is a Chinese herbal formula that has been shown to be beneficial in diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying mechanism of protection in nerve ischemia provided by TTF is still unclear. We hypothesized that TTF alleviates DPN via inhibition of ICAM-1 expression. Therefore, we tested the effect of TTF in a previously established DPN model, in which nerve injury was induced by ischemia/reperfusion in streptozotocin-induced diabetic rats. We found that the conduction velocity and amplitude of action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by TTF treatment. In addition, TTF treatment also attenuated the effect of DPN on other parameters including histology and ultrastructural changes, expression of ICAM-1, MPO, and TNF-alpha in rat sciatic nerves, and plasma sICAM-1 and MPO levels. Together, our data suggest that TTF treatment may alleviate DPN via ICAM-1 inhibition. PMID- 26539229 TI - Effect of Compound Chuanxiong Capsule on Inflammatory Reaction and PI3K/Akt/NF kappaB Signaling Pathway in Atherosclerosis. AB - Compound Chuanxiong Capsule (CCC), a Chinese herbal compound, can exhibit antiatherosclerotic effect; however, its mechanism is still unclear. This study is designed to study the mechanism of CCC on atherosclerosis in the ApoE-knockout (ApoE(-/-)) mice fed with a high-fat diet. After 6 weeks of high-fat feeding, 40 ApoE(-/-) mice were randomized (n = 10) and treated with lipitor, high-dose or low-dose CCC, or distilled water (ApoE(-/-) group) for 7 weeks. The blood lipids in serum and the plaque areas of the mice were measured and the mRNA expressions of phosphatidylinositol-3-kinases (PI3K), Akt, nuclear factor-kappa B (NF kappaB), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) of the aortae were determined. The data showed that CCC can significantly decrease the levels of blood lipids, atherosclerosis index, and plaque areas and increase collagen proportion in plaques as compared with the untreated mice (p < 0.05, p < 0.01). In addition, CCC can significantly reduce the mRNA expressions of PI3K, Akt, NF-kappaB, IL-6, and TNF-alpha in the mice fed with a high-fat diet (p < 0.001). Thus, we concluded that CCC can inhibit inflammatory reaction in the ApoE(-/-) mice fed with a high-fat diet. This mechanism may be attributed to regulating PI3K/Akt/NF-kappaB signaling pathway. PMID- 26539230 TI - Essential Experimental Methods for Identifying Bonghan Systems as a Basis for Korean Medicine: Focusing on Visual Materials from Original Papers and Modern Outcomes. AB - In the 1960s, through studies on Korean Medicine, Bonghan Kim proposed the Bonghan systems (BS) as the anatomical reality of the acupuncture meridians based on various experimental data. Since 2002, several groups, mainly led by a team at Seoul National University, who renamed the BS as the primo vascular system (PVS), have published around 70 papers showing biological structures corresponding to the BS. However, it is still difficult for other researchers to find them, especially under the skin, which Bonghan Kim first reported as acupuncture points, due to similar-looking biological tissues, for example, the lymphatic vessels, and such artifacts as blood clots or fascia debris. To solve these drawbacks, we examined the main methods for identifying the BS by comparing the original papers with the modern outcomes in terms of the common physical/chemical characteristics of the BS. In addition, effective methods of staining and microscopic observations discovered by modern teams are synthetically explained using visual materials such as diagrams and photos. Through the essentially organized methods in this review paper, we suggest that one can find the BS under the skin as putative acupuncture points by tracing the intraexternal BS, from which a new Korean Medicine will be born. PMID- 26539231 TI - A Modern Clinical Approach of the Traditional Korean Saam Acupuncture. AB - Saam acupuncture is one of the original therapeutic modalities representing traditional Korean medicine. It was originally described in a manuscript that is estimated to be published at some point between 1644 and 1742, in the middle of the Cho Sun dynasty, by a Korean Buddhist monk whose name is unknown. The principle of combining five shu points is based on the theory of Nan-jing. The treatment and diagnosis concepts in Saam acupuncture were mainly influenced by Dongeuibogam and Chimgoogyeong-heombang. The basic characteristic of combining five shu points in Saam acupuncture is the selection of the tonification and sedation points along the self-meridian and other meridians based on creation and governor relationships. Saam acupuncture clinical studies have mainly focused on musculoskeletal pain and autonomic nervous system regulation. From a neurophysiological perspective, Saam acupuncture, which involves five shu points as the main treatment aspect, has the advantage of increasing parasympathetic nerve activation and adjusting the balance of the autonomic nervous system. Inserting a needle into the skin layer while considering the respiratory phase and stimulating the needle gently and lightly could maximize the effect of Saam acupuncture. The specific Saam acupuncture prescribed should be identified on the basis of the neurobiological perspective. PMID- 26539232 TI - Serum Levels of Stress Hormones and Oxidative Stress Biomarkers Differ according to Sasang Constitutional Type. AB - Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females) were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS), and malondialdehyde (MDA) were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p < 0.1 in both sexes) and Soyangin (p < 0.05 in males and p < 0.1 in females). The adrenaline levels were also significantly lower in Taeumin than in Soumin (p < 0.05 in males and p < 0.1 in females) and Soyangin (p < 0.1 in males). Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p < 0.05 in males), whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p < 0.05 in males and p < 0.1 in females). Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types. PMID- 26539233 TI - Antihypertensive Effect of the GaMiSamHwangSaSimTang in Spontaneous Hypertensive Rats. AB - The present study was designed to evaluate the antihypertensive effect of GaMiSamHwangSaSimTang (HVC1), a 30% ethanol extract of a mixture comprising Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma, on spontaneous hypertensive rats (SHRs). The systolic blood pressure (SBP) was measured every 4 or 7 days using the noninvasive tail cuff system. The vasorelaxant effects on isolated aortic rings were evaluated. Aortic rings were contracted using phenylephrine (PE) or KCl, and the changes in tension were recorded via isometric transducers connected to a data acquisition system. In this study, oral administration of HVC1 decreased the SBP of SHRs over the experimental period. HVC1 induced concentration-dependent relaxation in the aortic rings that had been precontracted using PE or KCl. The vasorelaxant effects of HVC1 on endothelium intact aortic rings were inhibited by pretreatment with Nomega-Nitro-l-arginine methyl ester (L-NAME) or methylene blue. HVC1 inhibited the contraction induced by extracellular Ca(2+) in endothelium-denuded rat aortic rings that had been precontracted using PE or KCl. In conclusion, HVC1 reduced the SBP of SHR and relaxed isolated SHR aortic rings by upregulating NO formation and the NO-cGMP pathway and blocking the entry of extracellular Ca(2+) via receptor-operative Ca(2+) channel and voltage-dependent Ca(2+) channel. PMID- 26539234 TI - Trigonellae Semen Enhances Sperm Motility and the Expression of the Cation Sperm Channel Proteins in Mouse Testes. AB - Genetic defects during spermatogenesis can lead to a reduction in sperm motility and cause male infertility. The cation channels of sperm (CatSper) play a role in the regulation of hyperactivated sperm motility in mouse testes. The effect of Trigonellae Semen (TS) on the male reproductive system and CatSper protein in mouse testes during spermatogenesis was examined. C57BL/c mice were divided into the following five groups: normal, cyclophosphamide- (CP-) only treated (control group), and three groups treated with varying concentrations of TS with CP (100, 500, and 1000 mg/kg TS and 100 mg/kg CP). Real-time PCR, western blot analysis, and a testosterone immunoassay were performed to assess CatSper protein levels in the five groups. Additionally, sperm cell counts and motility were examined. Results indicate that sperm motility and sperm counts increased in the TS treated groups in a dose-dependent manner (p < 0.01). CatSper levels were also significantly higher in the TS treated groups compared to that of the control group (p < 0.001). Therefore, TS treatment could enhance sperm function by promoting spermatogenesis and the expression of CatSper proteins in mouse testes. PMID- 26539235 TI - Discrimination and Proper Use of Polygoni Multiflori Radix, Cynanchi Wilfordii Radix, and Cynanchi Auriculati Radix in Korea: A Descriptive Review. AB - Polygoni Multiflori Radix (PMR), Cynanchi Wilfordii Radix (CWR), and Cynanchi Auriculati Radix (CAR) are very popular herbal medicines in Traditional Korean Medicine, Traditional Chinese Medicine, and Kampo Medicine. However, the plant origins, efficacies, and traditional uses of these herbal medicines differ. In Korea, PMR is called Ha Su O (He Shou Wu in China), and CWR is called Baek Ha Su O or Baek Su O (Bai Shou Wu in China). Baek Su O refers to CWR in Korea and CAR in China. CAR has not been used as a traditional herbal medicine, and it cannot be legally used as a food or food ingredient in Korea. However, CAR is cultivated in Korea and imported from China. Because the morphology of CWR and CAR is very similar, they are often confused and misused in Korea. This review discusses the reasons for the confusion and misuse of these substances in Korea and provides the exact plant origins, efficacies, uses, components, and toxicities of PMR, CWR, and CAR so that they can be correctly understood and used. PMID- 26539236 TI - The Protective Effects of Curcumin on Obesity-Related Glomerulopathy Are Associated with Inhibition of Wnt/beta-Catenin Signaling Activation in Podocytes. AB - The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injury in vitro and obesity-related glomerulopathy (ORG) in vivo. Cellular experiments in vitro showed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experiments in vivo showed that curcumin significantly reduced the body weight, Lee's index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experiments in vitro and in vivo both displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, and beta-catenin and upregulate the phosphorylation level of beta-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/beta catenin signaling activation in podocytes. PMID- 26539237 TI - Development and Preliminary Validation of the Questionnaire (the First Edition) Based on TCM for Detecting Health Status in China. AB - Background. More and more people come to realize the importance of healthcare and early detecting of health status before becoming much more serious. Self perceived health is an easy, economic, and effective indicator of health, which has been widely applied in measuring health. In this paper, the development and preliminary validation of the questionnaire (the First Edition) based on TCM theory were described and combined with Manual Mental Health Pattern for detecting health status in community of Tianjin, China. Methods. Questionnaire validity and reliability were evaluated in a small sample as a pilot study. Analyses included tests for reliability and internal consistency, exploratory factor analysis, and tests for discriminative ability and convergent validity. Results. Overall, 294 of 303 participants completed the questionnaire (97.3%). The questionnaire included 49 items. Cronbach's alpha was 0.83. Factor analysis established 10 distinct domains. The Pearson's rho correlation between the total scores and MHP (SCL) was statistically significant (r = 0.43, P < 0.001). t-test revealed significant differences (P < 0.05) in total scores between the healthy and unhealthy results distinguished by physical examination. Conclusions. Questionnaire reliability and validity were acceptable. Further work and larger sample would be warranted to refine items that measure the health status, to improve the reliability and discriminated validity of the questionnaire. PMID- 26539238 TI - Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine Thiolactone In Vivo via Suppression of Oxidative Stress. AB - Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 MUg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 MUg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662. In vivo analysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks. Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARgamma-dependent suppression of oxidative stress. PMID- 26539239 TI - Effect of a Traditional Herbal Prescription, Kyung-Ok-Ko, on Male Mouse Spermatogenic Ability after Heat-Induced Damage. AB - Kyung-Ok-Ko (KOK), a well-known traditional Korean medicinal formula, has long been used to invigorate the essential qi. This use of KOK may be associated with reproductive ability as a more modern concept. The protective effect of KOK was evaluated against deterioration of testicular function induced by heat exposure in male mice. Male fertility was disrupted by scrotal heat stress at 43 degrees C for 5 weeks. KOK (0.25, 0.50, and 2.00 g/kg/day) was administered orally at 3 h after the stress. To evaluate the protective effect of KOK, body weight, testicular weight, sperm count, sperm motility, and histopathological changes in the testes were evaluated. KOK-treated mice significantly recovered their general health, as evidenced by body weight. KOK-treated mice also showed significantly higher testes weights, sperm counts, and sperm motility than did the heat stress group. KOK-treated mice significantly recovered the morphological appearance of the seminiferous tubules and seminiferous epithelium. Furthermore, KOK-treated mice significantly increased antioxidant enzyme activities and reduced the protein expressions of apoptosis in the testes. KOK significantly protects against heat-induced damage to testicular function in male mice by inhibiting oxidative stress and apoptosis, indicating that KOK may be an effective agent for treatment of heat-induced male infertility. PMID- 26539240 TI - Fetal facial expression in response to intravaginal music emission. AB - This study compared fetal response to musical stimuli applied intravaginally (intravaginal music [IVM]) with application via emitters placed on the mother's abdomen (abdominal music [ABM]). Responses were quantified by recording facial movements identified on 3D/4D ultrasound. One hundred and six normal pregnancies between 14 and 39 weeks of gestation were randomized to 3D/4D ultrasound with: (a) ABM with standard headphones (flute monody at 98.6 dB); (b) IVM with a specially designed device emitting the same monody at 53.7 dB; or (c) intravaginal vibration (IVV; 125 Hz) at 68 dB with the same device. Facial movements were quantified at baseline, during stimulation, and for 5 minutes after stimulation was discontinued. In fetuses at a gestational age of >16 weeks, IVM-elicited mouthing (MT) and tongue expulsion (TE) in 86.7% and 46.6% of fetuses, respectively, with significant differences when compared with ABM and IVV (p = 0.002 and p = 0.004, respectively). There were no changes from baseline in ABM and IVV. TE occurred >=5 times in 5 minutes in 13.3% with IVM. IVM was related with higher occurrence of MT (odds ratio = 10.980; 95% confidence interval = 3.105-47.546) and TE (odds ratio = 10.943; 95% confidence interval = 2.568-77.037). The frequency of TE with IVM increased significantly with gestational age (p = 0.024). Fetuses at 16-39 weeks of gestation respond to intravaginally emitted music with repetitive MT and TE movements not observed with ABM or IVV. Our findings suggest that neural pathways participating in the auditory-motor system are developed as early as gestational week 16. These findings might contribute to diagnostic methods for prenatal hearing screening, and research into fetal neurological stimulation. PMID- 26539241 TI - Short-term, high-fat diet accelerates disuse atrophy and protein degradation in a muscle-specific manner in mice. AB - BACKGROUND: A short-term high-fat diet impairs mitochondrial function and the ability of skeletal muscle to respond to growth stimuli, but it is unknown whether such a diet alters the ability to respond to atrophy signals. The purpose of this study was to determine whether rapid weigh gain induced by a high-fat (HF) diet accelerates denervation-induced muscle atrophy. METHODS: Adult, male mice (C57BL/6) were fed a control or HF (60 % calories as fat) diet for 3 weeks (3wHF). Sciatic nerve was sectioned unilaterally for the final 5 or 14 days of the diet. Soleus and extensor digitorum longus (EDL) muscles were removed and incubated in vitro to determine rates of protein degradation and subsequently homogenized for determination of protein levels of LC3, ubiquitination, myosin heavy chain (MHC) distribution, and mitochondrial subunits. RESULTS: When mice were fed the 3wHF diet, whole-body fat mass more than doubled, but basal (innervated) muscle weights, rates of protein degradation, LC3 content, mitochondrial protein content, and myosin isoform distribution were not significantly different than with the control diet in either soleus or EDL. However in the 14 day denervated soleus, the 3wHF diet significantly augmented loss of mass, proteolysis rate, amount of the autophagosome marker LC3 II, and the amount of overall ubiquitination as compared to the control fed mice. On the contrary, the 3wHF diet had no significant effect in the EDL on amount of mass loss, proteolysis rate, LC3 levels, or ubiquitination. Fourteen days denervation also induced a loss of mitochondrial proteins in the soleus but not the EDL, regardless of the diet. CONCLUSIONS: Taken together, a short-term, high-fat diet augments denervation muscle atrophy by induction of protein degradation in the mitochondria-rich soleus but not in the glycolytic EDL. These findings suggest that the denervation-induced loss of mitochondria and HF diet-induced impairment of mitochondrial function may combine to promote skeletal muscle atrophy. PMID- 26539243 TI - The 'Geographic Emission Benchmark' model: a baseline approach to measuring emissions associated with deforestation and degradation. AB - This paper proposes a new land-change model, the Geographic Emission Benchmark (GEB), as an approach to quantify land-cover changes associated with deforestation and forest degradation. The GEB is designed to determine 'baseline' activity data for reference levels. Unlike other models that forecast business-as usual future deforestation, the GEB internally (1) characterizes 'forest' and 'deforestation' with minimal processing and ground-truthing and (2) identifies 'deforestation hotspots' using open-source spatial methods to estimate regional rates of deforestation. The GEB also characterizes forest degradation and identifies leakage belts. This paper compares the accuracy of GEB with GEOMOD, a popular land-change model used in the UN-REDD (Reducing Emissions from Deforestation and Forest Degradation) Program. Using a case study of the Chinese tropics for comparison, GEB's projection is more accurate than GEOMOD's, as measured by Figure of Merit. Thus, the GEB produces baseline activity data that are moderately accurate for the setting of reference levels. PMID- 26539242 TI - Vaccination against hepatitis b virus: are Italian medical students sufficiently protected after the public vaccination programme? AB - BACKGROUND: The development of a vaccine against hepatitis B virus (HBV) has been a major achievement in terms of prevention of HBV infection. For the present study, we analysed the long-term immunogenicity and effectiveness of HBV vaccination among healthcare students with different working seniorities. METHODS: A cross-sectional study of undergraduate and postgraduate students attending the Medical School of the Second University of Naples was conducted between September 2012 and December 2014. HBV serum markers were determined and multivariate logistic regression analysis was used to identify factors associated with the level of long-term immunogenicity. RESULTS: Of the 2,932 subjects evaluated, only 33 (1.1 %) declared no history of vaccination. All vaccinated subjects were HBsAg/anti-HBc negative, 459 of which had an anti-HBs titre <10 IU/L. The latter were younger, more likely to be attending a healthcare profession school (i.e., dental hygienists, nursing, paediatric nursing, radiography and midwifery) than a medical school (at either undergraduate or postgraduate level) and more likely to have been vaccinated in infancy. CONCLUSION: The results of this study suggest that assessment of HBV serum markers in workers potentially exposed to hospital infections is useful to identify small numbers of unvaccinated subjects or vaccinated subjects with low antibody titre, all of whom should be referred to a booster series of vaccinations. PMID- 26539245 TI - Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA. AB - Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers. PMID- 26539244 TI - A Multiscale Constraints Method Localization of 3D Facial Feature Points. AB - It is an important task to locate facial feature points due to the widespread application of 3D human face models in medical fields. In this paper, we propose a 3D facial feature point localization method that combines the relative angle histograms with multiscale constraints. Firstly, the relative angle histogram of each vertex in a 3D point distribution model is calculated; then the cluster set of the facial feature points is determined using the cluster algorithm. Finally, the feature points are located precisely according to multiscale integral features. The experimental results show that the feature point localization accuracy of this algorithm is better than that of the localization method using the relative angle histograms. PMID- 26539246 TI - A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma. AB - Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality all over the world. Many studies have proposed that genes could be used to predict prognosis in KIRC. In this study, RNA expression data from next generation sequencing and clinical information of 523 patients downloaded from The Cancer Genome Atlas (TCGA) dataset were analyzed in order to identify the relationship between gene expression level and the prognosis of KIRC patients. A set of five genes that significantly associated with overall survival time was identified and a model containing these five genes was constructed by Cox regression analysis. By Kaplan-Meier and Receiver Operating Characteristic (ROC) analysis, we confirmed that the model had good sensitivity and specificity. In summary, expression of the five-gene model is associated with the prognosis outcomes of KIRC patients, and it may have an important clinical significance. PMID- 26539247 TI - The expression of perinatal depression in rural Ghana. AB - In low- and middle-income countries, perinatal depression (PND) has been associated with poor infant health outcomes, including frequency of infant diarrheal episodes, preterm delivery and low birth weight, and discontinuation or problems breastfeeding. Yet little is known about the awareness or expression of PND depression in Ghana. A total of 12 in-depth key-informant interviews were conducted with women who had experienced PND within the previous two-and-a-half years. Three focus-group discussions were conducted with new mothers (n = 11), grandmothers (n = 8), and fathers (n = 9) for contextual and supporting information. 'Thinking too much' was the term most commonly used to describe PND. The women saw their distress as caused largely by poverty, lack of social support, and domestic problems. Women sought help through family and religious organizations, rather than through medical services. Problems producing breast milk or breastfeeding were nearly universal complaints and suggest significant effects on infant health in the study area. These results present evidence to support the increasing consensus that depression presents in similar and disabling ways across cultures and contexts. This formative qualitative data is required to tailor depression prevention or treatment interventions to this particular socio-cultural context. PMID- 26539248 TI - Prenatal diagnosis of complete maternal uniparental isodisomy of chromosome 4 in a fetus without congenital abnormality or inherited disease-associated variations. AB - BACKGROUND: The prenatal diagnosis of subjects with complete uniparental isodisomy of chromosome 4 (iUPD4) has rarely been reported and poses a great challenge for genetic counseling. In this study, a prenatal case with a high (1 in 58) risk of Down syndrome was diagnosed with iUPD4 by combined chromosomal microarray analysis (CMA), whole exome sequencing (WES) and ultrasound morphology scan. RESULTS: By CMA, a pathogenic copy number variant was not detected; however, a complete maternal iUPD4 was identified in this fetus after analyzing the parental genotype results. To detect potentially autosomal recessive variants, WES was performed. Two missense and two frameshift variants were identified but were predicted with uncertain significance; none of the mutations were definitively associated with congenital abnormality or inherited disease. In addition, a detailed ultrasound morphology scan did not identify any structural abnormalities, facial dysmorphisms or intrauterine growth restriction. The family history was unremarkable. The couple was counseled with the prenatal diagnostic results, and they opted to give birth to the child. No phenotypic abnormalities were observed in this child after the first year of life. CONCLUSION: This study provides further evidence that iUPD4 can result in a healthy live birth and demonstrates that the combined use of CMA, WES and ultrasound technology provides additional information for the prenatal diagnosis and clinical management of rare UPD events. PMID- 26539249 TI - Next generation informatics for big data in precision medicine era. AB - The rise of data-intensive biology, advances in informatics technology, and changes in the way health care is delivered has created an compelling opportunity to allow us investigate biomedical questions in the context of "big data" and develop knowledge systems to support precision medicine. To promote such data mining and informatics technology development in precision medicine, we hosted two international informatics workshops in 2014: 1) the first workshop on Data Mining in Biomedical informatics and Healthcare, in conjunction with the 18th Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD 2014), and 2) the first workshop on Translational biomedical and clinical informatics, in conjunction with the 8th International Conference on Systems Biology and the 4th Translational Bioinformatics Conference (ISB/TBC 2014). This thematic issue of BioData Mining presents a series of selected papers from these two international workshops, aiming to address the data mining needs in the informatics field due to the deluge of "big data" generated by next generation biotechnologies such as next generation sequencing, metabolomics, and proteomics, as well as the structured and unstructured biomedical and healthcare data from electronic health records. We are grateful for the BioData Mining's willingness to produce this forward-looking thematic issue. PMID- 26539250 TI - Predictiveness curves in virtual screening. AB - BACKGROUND: In the present work, we aim to transfer to the field of virtual screening the predictiveness curve, a metric that has been advocated in clinical epidemiology. The literature describes the use of predictiveness curves to evaluate the performances of biological markers to formulate diagnoses, prognoses and assess disease risks, assess the fit of risk models, and estimate the clinical utility of a model when applied to a population. Similarly, we use logistic regression models to calculate activity probabilities related to the scores that the compounds obtained in virtual screening experiments. The predictiveness curve can provide an intuitive and graphical tool to compare the predictive power of virtual screening methods. RESULTS: Similarly to ROC curves, predictiveness curves are functions of the distribution of the scores and provide a common scale for the evaluation of virtual screening methods. Contrarily to ROC curves, the dispersion of the scores is well described by predictiveness curves. This property allows the quantification of the predictive performance of virtual screening methods on a fraction of a given molecular dataset and makes the predictiveness curve an efficient tool to address the early recognition problem. To this last end, we introduce the use of the total gain and partial total gain to quantify recognition and early recognition of active compounds attributed to the variations of the scores obtained with virtual screening methods. Additionally to its usefulness in the evaluation of virtual screening methods, predictiveness curves can be used to define optimal score thresholds for the selection of compounds to be tested experimentally in a drug discovery program. We illustrate the use of predictiveness curves as a complement to ROC on the results of a virtual screening of the Directory of Useful Decoys datasets using three different methods (Surflex-dock, ICM, Autodock Vina). CONCLUSION: The predictiveness curves cover different aspects of the predictive power of the scores, allowing a detailed evaluation of the performance of virtual screening methods. We believe predictiveness curves efficiently complete the set of tools available for the analysis of virtual screening results. PMID- 26539251 TI - Effect of Local Anesthetics on Human Mesenchymal Stromal Cell Secretion. AB - Anti-fibrotic and tissue regenerative mesenchymal stromal cell (MSC) properties are largely mediated by secreted cytokines and growth factors. MSCs are implanted to augment joint cartilage replacement and to treat diabetic ulcers and burn injuries simultaneously with local anesthetics, which reduce pain. However, the effect of anesthetics on therapeutic human MSC secretory function has not been evaluated. In order to assess the effect of local anesthetics on the MSC secretome, a panel of four anesthetics with different potencies - lidocaine, procaine, ropivacaine and bupivacaine - was evaluated. Since injured tissues secrete inflammatory cytokines, the effects of anesthetics on MSCs stimulated with tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were also measured. Dose dependent and anesthesia specific effects on cell viability, post exposure proliferation and secretory function were quantified using alamar blue reduction and immunoassays, respectively. Computational pathway analysis was performed to identify upstream regulators and molecular pathways likely associated with the effects of these chemicals on the MSC secretome. Our results indicated while neither lidocaine nor procaine greatly reduced unstimulated cell viability, ropivacaine and bupivacaine induced dose dependent viability decreases. This pattern was exaggerated in the simulated inflammatory environment. The reversibility of these effects after withdrawal of the anesthetics was attenuated for TNF-alpha/IFN-gamma-stimulated MSCs exposed to ropivacaine and bupivacaine. In addition, secretome analysis indicated that constitutive secretion changes were clearly affected by both anesthetic alone and anesthetic plus TNFalpha/IFNgamma cell stimulation, but the secretory pattern was drug specific and did not necessarily coincide with viability changes. Pathway analysis identified different intracellular regulators for stimulated and unstimulated MSCs. Within these groups, ropivacaine and bupivacaine appeared to act on MSCs similarly via the same regulatory mechanisms. Given the variable effect of local anesthetics on MSC viability and function, these studies underscore the need to evaluate MSC in the presence of medications, such as anesthetics, that are likely to accompany cell implantation. PMID- 26539252 TI - Options and Considerations for Adaptive Laboratory Experiments. AB - Motivated by laboratory experiments that fail to reach significance, we developed a small sample size approach to designing a subsequent experiment that controls overall type I error and achieves sufficient conditional power. We focus on experiments with leukemia cells, and use a specific example in Chronic Lymphocytic Leukemia to discuss unanticipated patient variance and difficult to predict interaction effect sizes. We emphasize the importance of achieving significance in the first run of an experiment, which results in simplifying the multiple considerations usually associated with interim analysis and decision making in adaptive clinical trials. Within the context of combination testing for an adaptive laboratory experiment, we show that a range of reasonable options for the futility cut-off, effect size estimation, and significance level for the first run provide similar power and expected overall sample size. We contrast this approach to a naive procedure in which a second unplanned experiment is run based on non-significance in the first experiment, and data are combined as if they were obtained from one run. PMID- 26539253 TI - DNA-methylation in C1R is a prognostic biomarker for acute myeloid leukemia. AB - BACKGROUND: Epigenetic aberrations play a central role in the pathophysiology of acute myeloid leukemia (AML). It has been shown that molecular signatures based on DNA-methylation (DNAm) patterns can be used for classification of the disease. In this study, we followed the hypothesis that DNAm at a single CpG site might support risk stratification in AML. FINDINGS: Using DNAm profiles of 194 patients from The Cancer Genome Atlas (TCGA), we identified a CpG site in complement component 1 subcomponent R (C1R) as best suited biomarker: patients with higher methylation at this CpG site (>27 % DNAm) reveal significantly longer overall survival (53 versus 11 months; P < 0.0001). This finding was validated in an independent set of 62 DNAm profiles of cytogenetically normal AML patients (P = 0.009) and with a region-specific pyrosequencing assay in 84 AML samples (P = 0.012). DNAm of C1R correlated with genomic DNAm and gene expression patterns, whereas there was only moderate association with gene expression levels of C1R. These results indicate that DNAm of C1R is a biomarker reflecting chromatin reorganization rather than being of pathophysiological relevance per se. Notably, DNAm of C1R was associated with occurrence of specific genomic mutations that are traditionally used for risk stratification in AML. Furthermore, DNAm of C1R correlates also with overall survival in several other types of cancer, but the prognostic relevance was less pronounced than in AML. CONCLUSIONS: Analysis of DNAm at C1R provides a simple, robust, and cost-effective biomarker to further complement risk assessment in AML. PMID- 26539254 TI - Chemical characterization and in vitro toxicity of diesel exhaust particulate matter generated under varying conditions. AB - Epidemiologic studies have linked diesel exhaust (DE) to cardiovascular and respiratory morbidity and mortality, as well as lung cancer. DE composition is known to vary with many factors, although it is unclear how this influences toxicity. We generated eight DE atmospheres by applying a 2*2*2 factorial design and altering three parameters in a controlled exposure facility: (1) engine load (27 vs 82 %), (2) particle aging (residence time ~5 s vs ~5 min prior to particle collection), and (3) oxidation (with or without ozonation during dilution). Selected exposure concentrations of both diesel exhaust particles (DEPs) and DE gases, DEP oxidative reactivity via DTT activity, and in vitro DEP toxicity in murine endothelial cells were measured for each DE atmosphere. Cell toxicity was assessed via measurement of cell proliferation (colony formation assay), cell viability (MTT assay), and wound healing (scratch assay). Differences in DE composition were observed as a function of engine load. The mean 1-nitropyrene concentration was 15 times higher and oxidative reactivity was two times higher for low engine load versus high load. There were no substantial differences in measured toxicity among the three DE exposure parameters. These results indicate that alteration of applied engine load shifts the composition and can modify the biological reactivity of DE. While engine conditions did not affect the selected in vitro toxicity measures, the change in oxidative reactivity suggests that toxicological studies with DE need to take into account engine conditions in characterizing biological effects. PMID- 26539256 TI - WHOLE BRAIN GROUP NETWORK ANALYSIS USING NETWORK BIAS AND VARIANCE PARAMETERS. AB - The disruption of normal function and connectivity of neural circuits is common across many diseases and disorders of the brain. This disruptive effect can be studied and analyzed using the brain's complex functional and structural connectivity network. Complex network measures from the field of graph theory have been used for this purpose in the literature. In this paper we have introduced a new approach for analyzing the brain connectivity network. In our approach the true connectivity network and each subject's bias and variance are estimated using a population of patients and healthy controls. These parameters can then be used to compare two groups of brain networks. We have used this approach for the comparison of the resting state functional MRI network of pediatric Tuberous Sclerosis Complex (TSC) patients and healthy subjects. We have shown that a significant difference between the two groups can be found. For validation, we have compared our findings with three well known complex network measures. PMID- 26539255 TI - EGCG Attenuates Uric Acid-Induced Inflammatory and Oxidative Stress Responses by Medicating the NOTCH Pathway. AB - BACKGROUND: The aim of this study is to investigate whether (-)-epigallocatechin 3-gallate (EGCG) can prevent the UA-induced inflammatory effect of human umbilical vein endothelial cells (HUVEC) and the involved mechanisms in vitro. METHODS: HUVEC were subjected to uric acid (UA) with or without EGCG treatment. RT-PCR and western blots were performed to determine the level of inflammation marker. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC lines were performed using RNA interference analyses. RESULTS: UA significantly increased the expressions of IL-6, ICAM-1, TNF-alpha, and MCP-1 and the production of ROS in HUVEC. Meanwhile, the expression of Notch-1 and its downstream effects significantly increased. Using siRNA, inhibition of Notch-1 signaling significantly impeded the expressions of inflammatory cytokines under UA treatment. Interestingly, EGCG suppressed the expressions of inflammatory cytokines and the generation of ROS. Western blot analysis of Notch-1 showed that EGCG significantly decreased the expressions of inflammatory cytokines through Notch-1 signaling pathways. CONCLUSIONS: In summary, our findings indicated that Notch-1 plays an important role in the UA-induced inflammatory response, and the downregulation of Notch-1 by EGCG could be an effective approach to decrease inflammation and oxidative stress induced by UA. PMID- 26539257 TI - Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain: A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease. AB - OBJECTIVE: This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). METHODS: Twenty Sprague Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. RESULTS: In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. CONCLUSION: Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD. PMID- 26539258 TI - Endovascular Treatment of Vertebral Artery Dissecting Aneurysms That Cause Subarachnoid Hemorrhage : Consideration of Therapeutic Approaches Relevant to the Angioarchitecture. AB - OBJECTIVE: Intracranial ruptured vertebral artery dissecting aneurysms (VADAns) are associated with high morbidity and mortality when left untreated due to the high likelihood of rebleeding. The present study aimed to establish an endovascular therapeutic strategy that focuses specifically on the angioarchitecture of ruptured VADAns. METHODS: Twenty-three patients with ruptured VADAn received endovascular treatment (EVT) over 7 years. The patient group included 14 women (60.9%) and 9 men (39.1%) between the ages of 39 and 72 years (mean age 54.2 years). Clinical data and radiologic findings were retrospectively analyzed. RESULTS: Four patients had aneurysms on the dominant vertebral artery. Fourteen (61%) aneurysms were located distal to the posterior inferior cerebellar artery (PICA). Six (26%) patients had an extracranial origin of the PICA on the ruptured VA, and 2 patients (9%) had bilateral VADAns. Eighteen patients (78%) were treated with internal coil trapping. Two patients (9%) required an adjunctive bypass procedure. Seven patients (30%) required stent supported endovascular procedures. Two patients experienced intra-procedural rupture during EVT, one of which was associated with a focal medullary infarction. Two patients (9%) exhibited recanalization of the VADAn during follow up, which required additional coiling. No recurrent hemorrhage was observed during the follow-up period. CONCLUSION: EVT of ruptured VADAns based on angioarchitecture is a feasible and effective armamentarium to prevent fatal hemorrhage recurrence with an acceptable low risk of procedural complications. Clinical outcomes depend mainly on the pre-procedural clinical state of the patient. Radiologic follow-up is necessary to prevent hemorrhage recurrence after EVT. PMID- 26539259 TI - Eleven Year's Single Center Experience of Endovascular Treatment of Anterior Communicating Artery Aneurysms: Focused on Digital Subtraction Angiography Follow Up Results. AB - OBJECTIVE: Anterior communicating artery (AcomA) aneurysms represent the most common intracranial aneurysms and challenging to treat due to complex vascularity. The purpose of this study was to report our experience of endovascular treatment of AcomA aneurysms. METHODS: Between January 2003 and December 2013, we retrospectively reviewed the medical records of 134 AcomA aneurysm patients available more than 6 months conventional angiographic and clinical follow-up results. We focused on aneurismal or AcomA vascular characters, angiographic and clinical follow-up results, and retreatment. RESULTS: The rate of ruptured cases was 75.4%, and the small (<10 mm) aneurysms were 96.3%. Based on the subtypes defined by dominance of A1, 79 patients (59%) had contralateral A1 hypoplasia or agenesis. The immediate post-procedural angiography confirmed complete occlusion in 75.4%, partial occlusion in 24.6%. Procedure related complications were observed in 25 (18.6%) patients. Most of the adverse events were asymptomatic. Follow-up conventional angiography at >=6 months was performed in all patients (mean 16.3 months) and major recanalization was noted in 6.7% and regrowth in one case. The aneurysm size (p=0.016), and initial treatment results (p=0.00) were statistically significant risk factors related to aneurysm recurrence. An overall improvement in mRS was observed during the clinical follow-up period and no rebleeding episode occurred. CONCLUSION: This study demonstrated that endovascular treatment is an effective treatment modality for AcomA aneurysms with low morbidity. Patients should take long term clinical and angiographic follow-up in order to assess the recurrence and warrant retreatment, especially ruptured, large, and initially incomplete occluded aneurysms. PMID- 26539260 TI - Angiographic and Clinical Factors Related with Good Functional Outcome after Mechanical Thrombectomy in Acute Cerebral Artery Occlusion. AB - OBJECTIVE: The aim of this study is to investigate good prognostic factors for an acute occlusion of a major cerebral artery using mechanical thrombectomy. METHODS: Between January 2013 to December 2014, 37 consecutive patients with acute occlusion of a major cerebral artery treated by mechanical thrombectomy with stent retrievers were conducted. We analyzed clinical and angiographic factors retrospectively. The collateral flow and the result of recanalization were sorted by grading systems. Outcome was assessed by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 90 days. We compared the various parameters between good and poor angiographic and clinical results. RESULTS: Twenty seven patients demonstrated good recanalization [Thrombolysis in Cerebral Infarction (TICI) 2b or 3] after thrombectomy. At the 90-day follow up, 19 patients had good (mRS, 0-2), 14 had moderate (3-4) and four had poor outcomes (5-6). The mRS of older patients (>=75 years) were poor than younger patients. Early recanalization, high Thrombolysis in Myocardial Infarction risk score, and low baseline NIHSS were closely related to 90-day mRS, whereas high TICI was related to both mRS and the decrease in the NIHSS. CONCLUSION: NIHSS decreased markedly only when recanalization was successful. A good mRS was related to low initial NIHSS, good collateral, and early successful recanalization. PMID- 26539261 TI - Endovascular Treatment of Ruptured Pericallosal Artery Aneurysms. AB - OBJECTIVE: Aneurysms arising from the pericallosal artery (PA) are uncommon and challenging to treat. The aim of this study was to report our experiences of the endovascular treatment of ruptured PA aneurysms. METHODS: From September 2003 to December 2013, 30 ruptured PA aneurysms in 30 patients were treated at our institution via an endovascular approach. Procedural data, clinical and angiographic results were retrospectively reviewed. RESULTS: Regarding immediate angiographic control, complete occlusion was achieved in 21 (70.0%) patients and near-complete occlusion in 9 (30.0%). Eight procedure-related complications occurred, including intraprocedural rupture and early rebleeding in three each, and thromboembolic event in two. At last follow-up, 18 patients were independent with a modified Rankin Scale (mRS) score of 0-2, and the other 12 were either dependent or had expired (mRS score, 3-6). Adjacent hematoma was found to be associated with an increased risk of poor clinical outcome. Seventeen of 23 surviving patients underwent follow-up conventional angiography (mean, 16.5 months). Results showed stable occlusion in 14 (82.4%), minor recanalization in two (11.8%), and major recanalization, which required recoiling, in one (5.9%). CONCLUSION: Our experiences demonstrate that endovascular treatment for a ruptured PA aneurysms is both feasible and effective. However, periprocedural rebleedings were found to occur far more often (20.0%) than is generally suspected and to be associated with preoperative contrast retention. Analysis showed existing adjacent hematoma is predictive of a poor clinical outcome. PMID- 26539262 TI - Effects of an Epithelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Add-on in Stereotactic Radiosurgery for Brain Metastases Originating from Non-Small-Cell Lung Cancer. AB - OBJECTIVE: This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. METHODS: We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. RESULTS: Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. CONCLUSIONS: Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment. PMID- 26539263 TI - Intracranial Hemangiopericytomas : A Retrospective Study of 15 Patients with a Special Review of Recurrence. AB - OBJECTIVE: Although surgical resection is used to treat meningeal hemangiopericytoma (MHPC), there is a high risk of subsequent recurrence. This study investigated factors associated with treatment outcomes and recurrence in patients who had undergone surgical resection of intracranial MHPC. METHODS: Fifteen patients underwent surgical treatments performed by one senior neurosurgeon between 1997 and 2013. Clinical data, radiologic images, surgical outcomes, recurrence, and other relevant characteristics were reviewed and analyzed. RESULTS: Fifteen patients were included in the analysis, 12 (80%) of whom had tumors in the supratentorial region, and 3 (20%) of whom had tumors in the infratentorial region. Complete resection was achieved in all 15 patients, and 3 (20%) patients were administered radiosurgery and conventional radiotherapy after surgery as adjuvant radiotherapy. Three patients developed recurrence, 2 of whom had not received adjuvant radiotherapy. In 1 of the patients who had not received adjuvant radiotherapy, recurrence developed at the original tumor site, 81 months after surgery. The other 2 recurrences occurred at other sites, 78 and 41 months after surgery. The 5- and 10-year overall survival rates were 88.3%, while the 5- and 10-year recurrence-free survival rates were 83% and 52%, respectively. Additionally the mean Ki-67 index differed significantly between patients who did and did not develop recurrence (43% vs. 14%; p=0.001). CONCLUSION: Because of the high risk of MHPC recurrence, MHPC tumors should be completely resected, whenever feasible. However, even when complete resection is achieved, adjuvant radiotherapy might be necessary to prevent recurrence. PMID- 26539264 TI - Efficacy and Safety of Fractionated Stereotactic Radiosurgery for Large Brain Metastases. AB - OBJECTIVE: To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs). METHODS: Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions. RESULTS: With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%). CONCLUSION: These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety. PMID- 26539265 TI - The Clinical and Radiological Effect of Abnormal Axis after Cervical Arthroplasty. AB - OBJECTIVE: The clinical outcomes according to the radiological results after cervical total disc replacement (TDR) are not well established. Here, the authors reviewed the clinical results according to the asymmetry in radiographs. METHODS: This retrospective analysis included patients after TDR (Mobi-C(r) disc) with at least 12 months follow up, and the clinical and radiological data were obtained preoperatively and postoperatively for 12 months. Clinical outcome measures numerical rating scale (NRS) score for neck pain, visual analog scale (VAS) for arm pain, and the Oswestry disability index (ODI) value. The asymmetries of TDRs were evaluated on the anterior-posterior (AP) and the lateral radiographs, and the radiographic adjacent segment degenerations were evaluated for 12 months. RESULTS: A total of 24 patients (one level cervical TDR; 10 male and 14 female; aged 41.50+/-8.35 years) were included in this study. The clinical results including NRS for neck pain, VAS for arm pain, and ODIs were similar between the normal and asymmetrized TDRs in AP and lateral radiographs. The radiographic adjacent segment degenerations were significantly increased in deviated TDRs (AP>10 mm asymmetry and lateral>10 mm asymmetry). CONCLUSION: Asymmetrical location of TDR is not related to the clinical outcomes, but related to the risk of radiographic adjacent disc segment degeneration. PMID- 26539266 TI - The Relationship between Neck Pain and Cervical Alignment in Young Female Nursing Staff. AB - OBJECTIVE: Degenerative changes in the cervical spine are commonly accompanied by cervical kyphosis which can cause neck pain. This study examined the relationship between neck pain and cervical alignment. METHODS: A total of 323 female nursing staff from our hospital were enrolled. Sagittal radiographs of the cervical spine, Body Mass Index (BMI), Visual Analogue Scale (VAS) measures of neck and arm pain, Neck Disability Index (NDI) and the Short Form (36) Health Survey (SF 36 scores) were obtained and reviewed retrospectively. Global lordosis (GL) of the cervical spine was measured on radiograph images. Correlations between GL and questionnaire scores were investigated using the following three methods : 1) correlation between GL and questionnaire scores among the entire sample; 2) subgroup analysis of patients with "kyphosis (KYP) : GL scores<0" vs. those with "lordosis (LOR) : GL scores>0" on questionnaire measures; and 3) subgroup analysis of patients with pain vs. those without pain, on GL and questionnaire measures. RESULTS: There was no significant correlation between GL and any questionnaire measure. There was a significant difference between the mean GLs of the KYP and LOR groups, but there were no group differences in BMI, age or any questionnaire measures. There was no difference between the pain (n=92) and pain free (n=231) groups in age, BMI or GL, but there were differences in neck, and arm pain, and physical function and NDI scores. CONCLUSIONS: Our data suggest that kyphotic deformity was not associated with neck pain. PMID- 26539267 TI - The Transmanubrial Approach for Cervicothoracic Junction Lesions : Feasibility, Limitations, and Advantages. AB - OBJECTIVE: We report on the technical feasibility and limitations of the transmanubrial approach for cervicothoracic junction (CTJ) lesions and emphasize the advantage of bisecting the upper part of the manubrium in an inverted Y shape. METHODS: Thirteen patients who underwent the fourteen transmanubrial approach for various CTJ lesions were enrolled during 2005-2014. For the evaluation of the accessibility for the CTJ lesion, we analyzed the two parallel line defined as a straight line parallel to the inferior and superior plateau of the upper and lower healthy vertebrae, the angle of the two parallel lines and the distance from the sternal notch to lines at the sternum on preoperative magnetic resonance images. Surgical limitations and perspectives, as well as postoperative clinical outcomes were evaluated retrospectively. RESULTS: The CTJ lesions were six metastases, three primary bone tumors, two herniated discs, and one each of a traumatic dislocation with syrinx formation and tuberculous spondylitis and ossification of the posterior longitudinal ligament. If two parallel lines pass below the sternal notch, the manubriotomy should be inevitably performed. The mean preoperative Visual analogue scale score was 8 (range, 5-10), which improved to 4 (range, 0-6) postoperatively. Seven cases showed an increase in Frankel score postoperatively. CONCLUSION: The spatial relationship between the sternal notch and the two parallel lines to the lesion was rational to determine the feasibility of manubriotomy. The transmanubrial approach for CTJ lesions can achieve favorable clinical outcomes by providing direct decompression of lesion and effective reconstruction. PMID- 26539268 TI - Brain Activation Evoked by Sensory Stimulation in Patients with Spinal Cord Injury : Functional Magnetic Resonance Imaging Correlations with Clinical Features. AB - OBJECTIVE: The purpose of this study is to determine whether the changes of contralateral sensorimotor cortical activation on functional magnetic resonance imaging (fMRI) can predict the neurological outcome among spinal cord injury (SCI) patients when the great toes are stimulated without notice. METHODS: This study enrolled a total of 49 patients with SCI and investigated each patient's preoperative fMRI, postoperative fMRI, American Spinal Injury Association (ASIA) score, and neuropathic pain occurrence. Patients were classified into 3 groups according to the change of blood oxygenation level dependent (BOLD) response on perioperative fMRI during proprioceptive stimulation with repetitive passive toe movements : 1) patients with a response of contralateral sensorimotor cortical activation in fMRI were categorized; 2) patients with a response in other regions; and 3) patients with no response. Correlation between the result of fMRI and each parameter was analyzed. RESULTS: In fMRI data, ASIA score was likely to show greater improvement in patients in group A compared to those belonging to group B or C (p<0.001). No statistical significance was observed between the result of fMRI and neuropathic pain (p=0.709). However, increase in neuropathic pain in response to the signal change of the ipsilateral frontal lobe on fMRI was statistically significant (p=0.030). CONCLUSION: When there was change of BOLD response at the contralateral sensorimotor cortex on perioperative fMRI after surgery, relief of neurological symptoms was highly likely for traumatic SCI patients. In addition, development of neuropathic pain was likely to occur when there was change of BOLD response at ipsilateral frontal lobe. PMID- 26539269 TI - Clinical Outcome of Treatment for Patients with Giant Cell Tumor in Spine. AB - OBJECTIVE: The treatment of giant cell tumor (GCT) is mainly performed surgically. However, GCT in spine seems difficult to treat because of the limited surgical accessibility and proximity. In this report, we analyzed the outcome of GCT treatment in spine. METHODS: Between 2000 and 2012, 19 patients received treatment for GCT in spine. Median age at their first diagnosis was 31 years, 10 patients were male, and 9 female. Fourteen tumors were located in the sacrum, 1 in cervical, 1 in thoracic and 3 in lumbar spine. As primary treatment, gross total removal (GTR) was done in 6 patients, and subtotal removal (STR) in 13 patients. Radiation therapy (RT) as an adjuvant therapy was performed in 2 cases in GTR group and 10 cases in STR group. RESULTS: During the follow-up, 7 patients had local recurrence (36.8%). The average period until recurrence after primary treatment was 14 months. No recurrence was detected in GTR group. Recurrence was noted in 7 out of 13 patients who underwent STR. These differences were statistically significant (p=0.024). A median of recurrence free period (RFP) was 84 months. Also average RFP of the RT group was 112 months, and non-RT group was 65 months. These differences were statistically significant (p=0.041). CONCLUSION: Treatment of choice for GCT in spine is a complete removal of tumor without neurological deficits. In case of incomplete removal, radiation therapy may be a useful adjuvant treatment modality. PMID- 26539270 TI - The Risk Factors for Hydrocephalus and Subdural Hygroma after Decompressive Craniectomy in Head Injured Patients. AB - OBJECTIVE: The present study aims to investigate 1) the risk factors for hydrocephalus and subdural hygroma (SDG) occurring after decompressive craniectomy (DC), and 2) the association between the type of SDG and hydrocephalus. METHODS: We retrospectively reviewed the clinical and radiological features of 92 patients who underwent DC procedures after severe head injuries. The risk factors for developing post-traumatic hydrocephalus (PTH) and SDG were analyzed. Types of SDGs were classified according to location and their relationship with hydrocephalus was investigated. RESULTS: Ultimately, 26.09% (24/92) of these patients developed PTH. In the univariate analyses, hydrocephalus was statically associated with large bone flap diameter, large craniectomy area, bilateral craniectomy, intraventricular hemorrhage, contralateral or interhemisheric SDGs, and delayed cranioplasty. However, in the multivariate analysis, only large craniectomy area (adjusted OR=4.66; p=0.0239) and contralateral SDG (adjusted OR=6.62; p=0.0105) were significant independent risk factors for developing hydrocephalus after DC. The incidence of overall SDGs after DC was 55.43% (51/92). Subgroup analysis results were separated by SDG types. Statistically significant associations between hydrocephalus were found in multivariate analysis in the contralateral (adjusted OR=5.58; p=0.0074) and interhemispheric (adjusted OR=17.63; p=0.0113) types. CONCLUSION: For patients who are subjected to DC following severe head trauma, hydrocephalus is associated with a large craniectomy area and contralateral SDG. For SDGs after DC that occur on the interhemispherical or controlateral side of the craniectomy, careful follow-up monitoring for the potential progression into hydrocephalus is needed. PMID- 26539271 TI - Clinical Factors and Perioperative Strategies Associated with Outcome in Preinjury Antiplatelet and Anticoagulation Therapy for Patients with Traumatic Brain Injuries. AB - OBJECTIVE: Long-term oral anticoagulation or antiplatelet therapy has been used with increasing frequency in the elderly. These patients are at increased risk of morbidity and mortality from expansion of intracranial hemorrhage. We conducted a single-center retrospective case control study to evaluate risk factors associated with outcomes and to identify the differences in outcome in traumatic brain injury between preinjury anticoagulation use and without anticoagulation. METHODS: A retrospective study of patients who underwent craniotomy or craniectomy for acute traumatic cerebral hemorrhage, between January 2005 and December 2014 was performed. RESULTS: A consecutive series of 50 patients were evaluated. The factors significantly differed between the two groups were initial Prothrombin Time-International Normalized Ratio, initial platelet count, initial Glasgow Coma Scale score, and postoperative intracranial bleeding. Mean Glasgow Outcome Scale (GOS) score were similar between the two groups. In the patient with low-energy trauma only, no significant differences in GOS score, postoperative bleeding and many other factors were observed. The contributing factors to postoperative bleeding was preinjury anticoagulation and its adjusted odds ratio was 12 [adjusted odds ratio (OR), 12.242; p=0.0070]. The contributing factors to low GOS scores, which mean unfavorable neurological outcomes, were age (adjusted OR, 1.073; p=0.039) and Rotterdam scale score for CT scans (adjusted OR, 3.123; p=0.0020). CONCLUSION: Preinjury anticoagulation therapy contributed significantly to the occurrence of postoperative bleeding. However, preinjury anticoagulation therapy in the patients with low-energy trauma did not contribute to the poor clinical outcomes or total hospital stay. Careful attention should be given to older patients and severity of hemorrhage on initial brain CT. PMID- 26539272 TI - Clinical Value of Procalcitonin in Patients with Spinal Infection. AB - OBJECTIVE: This study was designed to evaluation the diagnostic value of procalcitonin (PCT) in patients with spinal infection, compare to the classical biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count. METHODS: All patients who were diagnosed as a spinal infection between January, 2013 and July, 2014 were included in this study. Serum PCT, CRP, ESR, and WBC count were checked at initial hospital visit and once a week serially until they were discharged. Patient's medical history, causes and pathogens of spinal infection were reviewed. RESULTS: Total 34 (16 men, 18 women) patients were included in this study. Mean age of the patients was 65.6 year-old. Causes of spinal infection were pain block procedure (14, 41.2%) and post-operation (5, 14.7%). Out of 25 patients who showed elevated initial serum PCT level, 20 patients (80%) had a combined systemic infection. 14 patients (6.7%) had a sepsis, 3 patients (14.2%) had a urinary tract infection and 2 (9.6%) had a pneumonia. 14 patients (41.2%) showed elevation of serum PCT level during treatment. Among them, 9 patients (64.3%) had a combined infection such as sepsis and urinary tract infection. CONCLUSION: Serum CRP showed more sensitivity compared to serum PCT in patients with spinal infection. Patients with spinal infection who showed elevated serum PCT level should be investigated for combined infection and proper antibiotics should be applied. PMID- 26539273 TI - Tentorial Dural Arteriovenous Fistula Treated Using Transarterial Onyx Embolization. AB - Tentorial dural arteriovenous fistula (DAVF) is a rare vascular disease, which has high risk of intracranial hemorrhage. We present two cases of tentorial DAVF which were successfully treated with single trial of transarterial embolization using Onyx. We briefly reviewed the types of the tentorial DAVF and strategies of treatment. PMID- 26539274 TI - A Primary Ossifying Intracranial Myxoma Arising from the Ethmoid Sinus. AB - Myxomas are rare benign tumors that originate from mesenchymal tissue. They usually develop in the atrium of the heart, the skin, subcutaneous tissue, or bone. Involvement of the skull base with an intracranial extension is very rare and not well-described in the literature. We report a rare case of primary intracranial ossifying myxoma arising from the anterior skull base and mimicking a huge chondrosarcoma, and we review the relevant literature. PMID- 26539275 TI - Neurilemmoma of Deep Peroneal Nerve Sensory Branch : Thermographic Findings with Compression Test. AB - We report a case of neurilemmoma of deep peroneal nerve sensory branch that triggered sensory change with compression test on lower extremity. After resection of tumor, there are evoked thermal changes on pre- and post-operative infrared (IR) thermographic images. A 52-year-old female presented with low back pain, sciatica, and sensory change on the dorsal side of the right foot and big toe that has lasted for 9 months. She also presented with right tibial mass sized 1.2 cm by 1.4 cm. Ultrasonographic imaging revealed a peripheral nerve sheath tumor arising from the peroneal nerve. IR thermographic image showed hyperthermia when the neurilemoma induced sensory change with compression test on the fibular area, dorsum of foot, and big toe. After surgery, the symptoms and thermographic changes were relieved and disappeared. The clinical, surgical, radiographic, and thermographic perspectives regarding this case are discussed. PMID- 26539276 TI - A Large Ruptured Anterior Communicating Artery Aneurysm Presenting with Bitemporal Hemianopsia. AB - Anterior communicating artery (ACoA) aneurysms sometimes present with visual symptoms when they rupture or directly compress the optic nerve. Giant or large ACoA aneurysms producing bitemporal hemianopsia are extremely rare. Here we present an unusual case of bitemporal hemianopsia caused by a large intracranial aneurysm of the ACoA. A 41-year-old woman was admitted to our neurosurgical department with a sudden-onset bursting headache and visual impairment. On admission, her vision was decreased to finger counting at 30 cm in the left eye and 50 cm in the right eye, and a severe bitemporal hemianopsia was demonstrated on visual field testing. A brain computed tomography scan revealed a subarachnoid hemorrhage at the basal cistern, and conventional cerebral catheter angiography of the left internal carotid artery demonstrated an 18*8 mm dumbbell-shaped aneurysm at the ACoA. Microscopic aneurysmal clipping was performed. An ACoA aneurysm can produce visual field defects by compressing the optic chiasm or nerves. We emphasize that it is important to diagnose an aneurysm through cerebrovascular study to prevent confusing it with pituitary apoplexy. PMID- 26539277 TI - Idiopathic Spinal Cord Herniation Presented as Brown-Sequard Syndrome : A Case Report and Surgical Outcome. AB - Spinal cord herniation is a rare condition that has become increasingly recognised in the last few years. The authors report a case of idiopathic spinal cord herniation in a 33 year old woman performed with progressive Brown-Sequard syndrome. The diagnosis was made on MR imaging. After repairing the herniation, the patient made a gradual improvement. Potential causes are discussed, including a possible role of dural defect. In conclusion, idiopathic spinal cord herniation is a potentially treatable condition that should be more readily diagnosed that increasing awareness and improved imaging techniques. PMID- 26539278 TI - Post-Traumatic Arteriovenous Fistula of the Scalp. AB - Arteriovenous fistula of the scalp is relatively rare disease. We report a traumatic arteriovenous fistula of the scalp treated with complete surgical excision and review the literature with regard to etiology, pathogenesis, and management of these unusual lesions. PMID- 26539279 TI - Spontaneous Resolution of a Large Chronic Subdural Hematoma Which Required Surgical Decompression. AB - We report on a case of an 87-year-old woman who showed spontaneous resolution of a large chronic subdural hematoma which required surgical decompression. She had suffered from confused mentality and right side weakness of motor grade II for 10 days. The initial brain CT scan showed a 22 mm thick low density lesion located in the left fronto-temporo-parietal region with midline shift (12 mm) which required emergency decompression. However, because she and her family did not want surgery, she was followed up in the outpatient clinic. Five months later, follow up brain CT showed that the CSDH had disappeared and the patient became neurologically normal. The reasons for spontaneous resolution of CSDH remain unclear. We discuss the possible relation between mechanisms of physio pathogenesis and spontaneous resolution of a large chronic subdural hematoma (CSH) in an elderly patient. PMID- 26539280 TI - Surgical Treatment of a Life-Threatening Large Retropharyngeal Hematoma after Minor Trauma : Two Case Reports and a Literature Review. AB - Only a few cases of anterior longitudinal ligament (ALL) injury related with retropharyngeal hematoma without fracture have previously been reported. The treatment of choice for retropharyngeal hematoma is generally considered to be conservative care, but we believe that early surgery of this pathology would be better in certain situations. Here, we describe two cases with life-threatening large retropharyngeal hematomas related with ALL injuries and operated on at an early stage. Two previously healthy patients visited the emergency room with neck pain and dyspnea after falling. Serious neck swelling was observed and lateral neck X-ray showed severe widening of the prevertebral space. Due to dyspnea progression, emergency endotracheal intubation was performed. Although there was no primary cause of the retropharyngeal hematoma on preoperative examination, ALL tearing was intraoperatively confirmed during early surgery. The in-hospital evolutions of the patients were favorable after surgery. We should bear in mind the possibility of ALL injury and perform early surgery where possible given the earlier convalescence and good prognosis. PMID- 26539281 TI - Application of Mobile Phones in Ophthalmology. PMID- 26539282 TI - Rho-Associated Kinase Inhibitors: Potential Future Treatments for Glaucoma. PMID- 26539283 TI - Efficacy of Reciproc((r)) and Profile((r)) Instruments in the Removal of Gutta Percha from Straight and Curved Root Canals ex Vivo. AB - OBJECTIVES: To compare the efficacy of Reciproc((r)) (VDW GmbH) and ProFile((r)) (Dentsply Maillefer) instruments at removing gutta-percha from straight and curved root canals ex vivo filled using the cold lateral condensation and GuttaMaster((r)) (VDW GmbH) techniques. MATERIAL AND METHODS: Forty mesial roots of mandibular molars with two curved canals and 80 single-rooted teeth with straight root canals, a total of 160 root canals, were randomly assigned to eight groups (canals per group = 20) according to filling technique, retreatment instrument and root canal curvature as follows: Group I, cold lateral condensation/ProFile((r))/straight; Group II, cold lateral condensation/ProFile((r))/curved; Group III, cold lateral condensation/Reciproc((r))/straight; Group IV, cold lateral condensation/Reciproc((r))/curved; Group V, GuttaMaster((r))/ProFile((r))/straight; Group VI, GuttaMaster((r))/ProFile((r))/curved; Group VII, GuttaMaster((r))/Reciproc((r))/straight; and Group VIII, GuttaMaster((r))/Reciproc((r))/curved. The following data were recorded: procedural errors, retreatment duration and canal wall cleanliness. Means and standard deviations were calculated and analysed using the Kruskal-Wallis test, one-way analysis of variance and Tukey's test (P < 0.05). RESULTS: Reciproc((r)) instruments were significantly faster than ProFile((r)) instruments at removing GuttaMaster((r)) from both straight (P = 0.0001) and curved (P = 0.0003) root canals. Reciproc((r)) were statistically more effective than ProFile((r)) instruments in removing GuttaMaster((r)) from straight root canals (P = 0.021). Regardless of filling technique or retreatment instrument, gutta-percha was removed more rapidly from curved than from straight root canals (P = 0.0001). CONCLUSIONS: Neither system completely removed filling material from the root canals. Compared with ProFile((r)) instruments, Reciproc((r)) instruments removed GuttaMaster((r)) filling material from straight and curved root canals more rapidly. PMID- 26539284 TI - Effectiveness of a Motivation and Practical Skills Development Methods on the Oral Hygiene of Orphans Children in Kaunas, Lithuania. AB - OBJECTIVES: The aim of this study was to evaluate the effect of a motivation and practical skills development methods on the oral hygiene of orphans. MATERIAL AND METHODS: Sixty eight orphans aged between 7 and 17 years from two orphanages in Kaunas were divided into two groups: practical application group and motivation group. Children were clinically examined by determining their oral hygiene status using Silness-Loe plaque index. Questionnaire was used to estimate the oral hygiene knowledge and practices at baseline and after 3 months. Statistical analysis included: Chi-square test (chi(2)), Fisher's exact test, Student's t test, nonparametric Mann-Whitney test, Spearman's rho correlation coefficient and Kappa coefficient. RESULTS: All children had a plaque on at least one tooth in both groups: motivation 1.14 (SD 0.51), practical application 1.08 (SD 0.4) (P = 0.58). Girls in both groups showed significantly better oral hygiene than boys (P < 0.001). After 3 months educational program oral hygiene status improved in both groups significantly 0.4 (SD 0.35) (P < 0.001). Significantly better oral hygiene was determined in practical application group 0.19 (SD 0.27) in comparison with motivation group 0.55 (SD 0.32) (P < 0.001). By comparing results of first and second questionnaire surveys on use of soft drinks, the statistically significant decline of their use was in both groups (P = 0.004). CONCLUSIONS: Educational programs are effective in improving oral hygiene, especially when they're based on practical skills training. PMID- 26539285 TI - Impact of Dentofacial Deformity on Quality of Life: Age and Gender Differences Evaluated Through OQLQ, OHIP and SF36. AB - OBJECTIVES: The aim of this study was to verify the impact of dentofacial deformity on quality of life and explore gender and age differences. MATERIAL AND METHODS: The impact of dentofacial deformity (DD) on quality of life was evaluated through questionnaires; Short Form Health Survey (SF36), Oral Health Impact Profile Questionnaire (OHIP), Orthognathic Quality of Life Questionnaire (OQLQ) and a single question answered by a Visual Analogue Scale. RESULTS: Significant differences between male and female patients were observed in domains of OQLQ (oral function, P = 0.006; awareness of facial deformity, P = 0.018; and facial aesthetics, P < 0.001) and OHIP (physical pain, P = 0.006; psychological discomfort, P = 0.007; psychological disability, P = 0.006; and handicap, P = 0.01). CONCLUSIONS: The impact of dentofacial deformity was more pronounced in female Brazilian population. Age of patients with dentofacial deformity produced impacts over quality of life in different ways and according to the applied questionnaire and the interaction between age and gender may also produce different impacts in patients with dentofacial deformity. The domains of Orthognathic Quality of Life Questionnaire, Oral Health Impact Profile Questionnaire and Short Form Health Survey showed unaccepted distances in the pattern of answer rising doubts of their ability to assess quality of life as a generic and broad concept. There is a necessity to create a single quality of life instrument capable to measure impacts with sensitivity and specificity and from a generic concept to condition-specific health problem. PMID- 26539286 TI - Scapular Free Vascularised Bone Flaps for Mandibular Reconstruction: Are Dental Implants Possible? AB - OBJECTIVES: Free fibula flap remains the flap of choice for reconstruction of mandibular defects. If free fibula flap is not possible, the subscapular system of flaps is a valid option. In this study, we evaluated the possibility of dental implant placement in patients receiving a scapular free flap for oromandibular reconstruction. MATERIAL AND METHODS: We retrospectively reviewed 10 patients undergoing mandible reconstruction with a subscapular system free-tissue (lateral border of the scapula) transfer at the University Hospital Zurich between January 1, 2010 and January 1, 2013. Bone density in cortical and cancellous bone was measured in Hounsfield units (HU). Changes of bone density, height and width were analysed using IBM SPSS Statistics 22. Comparisons of bone dimensions as well as bone density were performed using a chi-square test. RESULTS: Ten patients were included. Implantation was conducted in 50%. However, all patients could have received dental implants considering bone stock. Loss of bone height and width were significant (P < 0.001). There was a statistical significant increase in bone density in cortical (P < 0.001) and cancellous (P = 0.004) bone. CONCLUSIONS: Dental implants are possible after scapular free flap reconstruction of oromandibular defects. Bone height and width were reduced, while bone density increased with time. PMID- 26539287 TI - Development of a Titanium Plate for Mandibular Angle Fractures with a Bone Defect in the Lower Border: Finite Element Analysis and Mechanical Test. AB - OBJECTIVES: The aim of the present study was to develop a plate to treat mandibular angle fractures using the finite element method and mechanical testing. MATERIAL AND METHODS: A three-dimensional model of a fractured mandible was generated using Rhinoceros 4.0 software. The models were exported to ANSYS((r)), in which a static application of displacement (3 mm) was performed in the first molar region. Three groups were assessed according to the method of internal fixation (2 mm system): two non-locking plates; two locking plates and a new design locking plate. The computational model was transferred to an in vitro experiment with polyurethane mandibles. Each group contained five samples and was subjected to a linear loading test in a universal testing machine. RESULTS: A balanced distribution of stress was associated with the new plate design. This plate modified the mechanical behavior of the fractured region, with less displacement between the fractured segments. In the mechanical test, the group with two locking plates exhibited greater resistance to the 3 mm displacement, with a statistically significant difference when compared with the new plate group (ANOVA, P = 0.016). CONCLUSIONS: The new plate exhibited a more balanced distribution of stress. However, the group with two locking plates exhibited greater mechanical resistance. PMID- 26539289 TI - Treatment of acute rhinitis with a nasal spray containing tramazoline and essential oils: a multicenter, uncontrolled, observational trial. AB - BACKGROUND: In this observational trial, data were collected on the effectiveness and tolerability/safety of a nasal spray containing tramazoline and essential oils (trade name Rhinospray((r)) Plus) used for symptomatic treatment of acute rhinitis due to common cold. METHODS: The trial was performed in 300 children, adolescents and adults, who were to be treated with Rhinospray((r)) Plus for up to 4 times per day for up to 10 days. Primary endpoints were the change from baseline to final visit in the mean of three single symptom scores (blocked nose, sneezing, and runny nose) and the mean improvement in two quality-of-life parameters (ability to perform normal daytime activities and quality of sleep). RESULTS: A total of 108 children, 30 adolescents and 162 adults were treated with Rhinospray((r)) Plus. No patient discontinued prematurely. There was a mean reduction of 2.0 +/- 0.6 (standard deviation) in nasal symptom scores from baseline to final visit; 297 of 300 of patients (99.0 %) reported an improvement. The mean value for improvement in quality-of-life parameters was 1.3 +/- 0.5. Improvement in daytime activities was reported by all 300 patients (100.0 %) and in quality of sleep by 292 patients (97.4 %). Effectiveness and tolerability were rated as 'very good' or 'good' by 95.4 % and 97.4 % of patients, respectively; the investigators rated effectiveness and tolerability as 'very good' or 'good' for 97.4 % and 100.0 % of patients, respectively. No adverse events were reported. CONCLUSIONS: Community-based patients reported a relief in acute rhinitis symptoms and improvement in quality of life as a result of treatment with Rhinospray((r)) Plus. Treatment was well-tolerated. PMID- 26539290 TI - Rampant software errors undermine scientific results. AB - Errors in scientific results due to software bugs are not limited to a few high profile cases that lead to retractions and are widely reported. Here I estimate that in fact most scientific results are probably wrong if data have passed through a computer, and that these errors may remain largely undetected. The opportunities for both subtle and profound errors in software and data management are boundless, yet they remain surprisingly underappreciated. PMID- 26539291 TI - Biomedical publications on Ebola and the 2014 outbreak. AB - In this research note we examine the biomedical publication output about Ebola in 2014. We show that the volume of publications has dramatically increased in the past year. The rise reflects an impressive growth starting in the month of August, concomitant with or following the surge in infections, deaths and coverage in news and social media. Though non-research articles have been the major contributors to this growth, there has been a substantial increase in original research articles too, including many papers of basic science. The United States has been the country with the highest number of research articles, followed by Canada and the United Kingdom. We present a comprehensive set of charts and facts that, by describing the volumes and nature of publications in 2014, show how the scientific community has responded to the Ebola outbreak and how it might respond to future similar global threats and media events. This information will assist scholars and policymakers in their efforts to improve scientific research policies with the goal of maximizing both public health and knowledge advancement. PMID- 26539288 TI - The function, regulation and therapeutic implications of the tumor suppressor protein, PML. AB - The tumor suppressor protein, promyelocytic leukemia protein (PML), was originally identified in acute promyelocytic leukemia due to a chromosomal translocation between chromosomes 15 and 17. PML is the core component of subnuclear structures called PML nuclear bodies (PML-NBs), which are disrupted in acute promyelocytic leukemia cells. PML plays important roles in cell cycle regulation, survival and apoptosis, and inactivation or down-regulation of PML is frequently found in cancer cells. More than 120 proteins have been experimentally identified to physically associate with PML, and most of them either transiently or constitutively co-localize with PML-NBs. These interactions are associated with many cellular processes, including cell cycle arrest, apoptosis, senescence, transcriptional regulation, DNA repair and intermediary metabolism. Importantly, PML inactivation in cancer cells can occur at the transcriptional-, translational or post-translational- levels. However, only a few somatic mutations have been found in cancer cells. A better understanding of its regulation and its role in tumor suppression will provide potential therapeutic opportunities. In this review, we discuss the role of PML in multiple tumor suppression pathways and summarize the players and stimuli that control PML protein expression or subcellular distribution. PMID- 26539292 TI - Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation. AB - Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation. PMID- 26539293 TI - Dual mechanisms governing reward-driven perceptual learning. AB - In this review, we explore how reward signals shape perceptual learning in animals and humans. Perceptual learning is the well-established phenomenon by which extensive practice elicits selective improvement in one's perceptual discrimination of basic visual features, such as oriented lines or moving stimuli. While perceptual learning has long been thought to rely on 'top-down' processes, such as attention and decision-making, a wave of recent findings suggests that these higher-level processes are, in fact, not necessary. Rather, these recent findings indicate that reward signals alone, in the absence of the contribution of higher-level cognitive processes, are sufficient to drive the benefits of perceptual learning. Here, we will review the literature tying reward signals to perceptual learning. Based on these findings, we propose dual underlying mechanisms that give rise to perceptual learning: one mechanism that operates 'automatically' and is tied directly to reward signals, and another mechanism that involves more 'top-down', goal-directed computations. PMID- 26539294 TI - Antibiotic trends of Klebsiella pneumoniae and Acinetobacter baumannii resistance indicators in an intensive care unit of Southern Italy, 2008-2013. AB - BACKGROUND: The overuse of antimicrobials is one of the main factors responsible for the development and spread of antimicrobial resistance, together with other causes, such as intra- and inter-hospital spread of resistant microorganisms and infection control policies and practices. The objective of the present study is to report the trends of Klebsiella pneumoniae and Acinetobacter baumannii antimicrobial resistance indicators in an Italian intensive care unit (ICU) during a six-year period, from 2008 to 2013. METHODS: Susceptibility data and annual antibiotic consumptions in the ICU were retrospectively obtained from the clinical laboratory and the pharmacy. Trends over time of resistance rates (RRs) and of incidence densities of resistant isolates were determined by linear regression. RESULTS: Isolation density of A. baumannii increased significantly from 2008 (20.4 per 1,000 patient-days) to 2013 (58.1 per 1,000 patient-days) and of K. pneumoniae from 2010 (22.3 per 1,000 patient-days) to 2013 (55.9 per 1,000 patient-days). RRs of third-generation cephalosporins (3GCs)-resistant K. pneumoniae (from 2010: 41.9 %, to 2012: 87.0 %), of carbapenem-resistant K. pneumoniae (from 2008: 0 %, to 2013: 59.2 %), and of carbapenem-resistant A. baumannii (from 2008: 87.5 %, to 2013: 96.6 %) showed significant increasing trends. Carbapenems was the main antibiotic class consumed (24.9 % of the total antimicrobial usage density), followed by 3GCs (21.0 %), fluoroquinolones (20.6 %), aminoglycosides (17.3 %), penicillins (15.1 %) and glycopeptides (1.1 %). Carbapenems consumption decreased from 2008 to 2012 and then increased in 2013. Glycopeptides consumption decreased from 2008 to 2011 and then increased in 2013. Aminoglycosides consumption decreased from 2008 to 2010 and increased from 2012 to 2013. Finally, 3GC, penicillins and fluoroquinolones consumptions decreased from 2012 to 2013. CONCLUSIONS: RRs of carbapenem-resistant A. baumannii and of carbapenem- and 3GC-resistant K. pneumoniae were higher than those for Europe. Our findings highlight the necessity to implement an integrated system for monitoring not only consumption of antibiotics and resistance profiles but also the clonality of alert microorganisms in the ICU for effective infection control. PMID- 26539295 TI - The effect of preheated versus room-temperature skin disinfection on bacterial colonization during pacemaker device implantation: a randomized controlled non inferiority trial. AB - BACKGROUND: In clinical practice, patients who are awake often comment that cold surgical skin disinfectant is unpleasant. This is not only a problem of patients' experience; heat loss during the disinfection process is a problem that can result in hypothermia. Evidence for the efficacy of preheated disinfection is scarce. We tested whether preheated skin disinfectant was non-inferior to room temperature skin disinfectant on reducing bacterial colonization during pacemaker implantation. METHODS: This randomized, controlled, non-inferiority trial included 220 patients allocated to skin disinfection with preheated (36 degrees C) or room-temperature (20 degrees C) chlorhexidine solution in 70 % ethanol. Cultures were obtained by swabbing at 4 time-points; 1) before skin disinfection (skin surface), 2) after skin disinfection (skin surface), 3) after the incision (subcutaneously in the wound), and 4) before suturing (subcutaneously in the wound). RESULTS: The absolute difference in growth between patients treated with preheated versus room-temperature skin disinfectant was zero (90 % CI -0.101 to 0.101; preheated: 30 of 105 [28.6 %] vs. room-temperature: 32 of 112 [28.6 %]). The pre-specified margin for statistical non-inferiority in the protocol was set at 10 % for the preheated disinfectant. There were no significant differences between groups regarding SSIs three month postoperatively, which occurred in 0.9 % (1 of 108) treated with preheated and 1.8 % (2 of 112) treated with room temperature skin disinfectant. CONCLUSION: Preheated skin disinfection is non inferior to room-temperature disinfection in bacterial reduction. We therefore suggest that preheated skin disinfection become routine in clean surgery. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCTO2260479). PMID- 26539296 TI - Mechanisms of osteolytic and osteoblastic skeletal lesions. AB - The bone is a frequent site for tumor metastasis, and cancer in the bone results in marked disturbances of bone remodeling that can be lytic, blastic or a combination of the two. Patients with advanced malignancies that have metastasized to the bone frequently suffer from debilitating skeletal-related events, including pathologic fractures, spinal cord compression syndromes, disorders of calcium and phosphate homeostasis and severe cancer-related pain. This review will discuss recent studies on the mechanisms responsible for osteolytic and osteoblastic metastasis and how their identification has resulted in the development of new agents for patients with metastatic bone disease. PMID- 26539297 TI - Optimization of sonochemical degradation of tetracycline in aqueous solution using sono-activated persulfate process. AB - BACKGROUND: In this study, a central composite design (CCD) was used for modeling and optimizing the operation parameters such as pH, initial tetracycline and persulfate concentration and reaction time on the tetracycline degradation using sono-activated persulfate process. The effect of temperature, degradation kinetics and mineralization, were also investigated. RESULTS: The results from CCD indicated that a quadratic model was appropriate to fit the experimental data (p < 0.0001) and maximum degradation of 95.01 % was predicted at pH = 10, persulfate concentration = 4 mM, initial tetracycline concentration = 30.05 mg/L, and reaction time = 119.99 min. Analysis of response surface plots revealed a significant positive effect of pH, persulfate concentration and reaction time, a negative effect of tetracycline concentration. The degradation process followed the pseudo-first-order kinetic. The activation energy value of 32.01 kJ/mol was obtained for US/S2O8 (2-) process. Under the optimum condition, the removal efficiency of COD and TOC reached to 72.8 % and 59.7 %, respectively. The changes of UV-Vis spectra during the process was investigated. The possible degradation pathway of tetracycline based on loses of N-methyl, hydroxyl, and amino groups was proposed. CONCLUSIONS: This study indicated that sono-activated persulfate process was found to be a promising method for the degradation of tetracycline. PMID- 26539298 TI - Influence of Deceased Donor and Pretransplant Recipient Parameters on Early Overall Kidney Graft-Survival in Germany. AB - Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 4411, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013-1.027] per year), donor size (0.985 [0.977-0.993] per cm), donor's creatinine at admission (1.002 [1.001-1.004] per umol/L), donor treatment with catecholamine (0.757 [0.635 0.901]), and reduced graft-quality at procurement (1.549 [1.217-1.973]), as well as recipient age (1.012 [1.003-1.021] per year), actual panel reactive antibodies (1.007 [1.002-1.011] per percent), retransplantation (1.850 [1.484-2.306]), recipient's cardiovascular comorbidity (1.436 [1.212-1.701]), and use of IL2 receptor antibodies for induction (0.741 [0.619-0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care. PMID- 26539299 TI - Associations among Physical Activity, Diet, and Obesity Measures Change during Adolescence. AB - Background. Obesity in youth is highly prevalent. Physical activity and diet are influential in obesity development. However, there is a knowledge gap regarding links between activity and diet quality and their combined influence on obesity during adolescence. Objectives. We used five years of data from 2379 adolescent girls in the National Heart Lung and Blood Institute Growth and Health Study to evaluate the association between physical activity and diet quality during adolescence and to assess both as correlates of obesity. Design. Diet, activity, and body composition measures were evaluated pairwise for correlation. A canonical correlation analysis was used to evaluate relationships within and between variable groups. All statistics were examined for trends over time. Results. We found positive correlations between physical activity and diet quality that became stronger with age. Additionally we discovered an age-related decrease in association between obesity correlates and body composition. Conclusion. These results suggest that while health behaviors, like diet and activity, become more closely linked during growth, obesity becomes less influenced by health behaviors and other factors. This should motivate focus on juvenile obesity prevention capitalizing on the pliable framework for establishing healthy diet and physical activity patterns while impact on body composition is greatest. PMID- 26539300 TI - Manic Symptoms during a Switch from Paliperidone ER to Paliperidone Palmitate in a Patient with Schizophrenia. AB - Some antipsychotic drugs have treatment efficacy for mania and bipolar disorder. However, these drugs may rarely cause manic symptoms in some schizophrenic patients. We hereby report a 22-year-old female patient with schizophrenia who experienced a manic episode during a switch from paliperidone ER to paliperidone palmitate. This case is an important reminder that an abrupt switch from oral paliperidone to paliperidone palmitate may predispose certain patients to hypomanic or manic symptoms. PMID- 26539301 TI - Anorectal Malformation: Paediatric Problem Presenting in Adult. AB - This is a case report of 22-year-old girl admitted with abdominal distension, vomiting, and chronic constipation since birth. Abdomen was distended, and perineal examination revealed imperforate anus with vestibular fistula (ARM). So far worldwide very few cases have been reported about anorectal malformation presenting in adulthood, and thus extremely little data is available in the literature about an ideal management of anorectal malformation in adults. In our case in the treatment instead of conventional procedure of posterior sagittal anorectoplasty (PSARP) anal transposition was done and till two years after the definitive treatment during follow-up patient has been doing well with Kelly's score of six. Our experience suggests that anal transposition provides satisfactory outcome in adults presenting late with anorectal malformation. PMID- 26539302 TI - The Cannabis Dilemma: A Review of Its Associated Risks and Clinical Efficacy. AB - Cannabis, also known as marijuana, has 9-tetrahydrocannabinol as the main constituent. There has been strict legislation governing the utilization of cannabis locally and worldwide. However, there has been an increasing push to make cannabis legalized, in view of its potential medical and therapeutic effects, for various medical disorders ranging from development disorders to cancer treatment, and being an adjunctive medication for various neurological conditions. It is the aim of this review paper to explore the evidence base for its proposed therapeutic efficacy and to compare the evidence base supporting its proposed therapeutic efficacy with its known and well-researched medical and psychiatric side effects. PMID- 26539303 TI - Minimal Clinically Important Difference on Parkinson's Disease Sleep Scale 2nd Version. AB - Background and Aims. The aim of the present study was to determine the estimates of minimal clinically important difference for Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score and dimensions. Methods. The subject population consisted of 413 PD patients. At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rating Scale, and PDSS-2 were assessed. Nine months later the PDSS-2 was reevaluated with the Patient-Reported Global Impression Improvement Scale. Both anchor-based techniques (within patients' score change method and sensitivity- and specificity-based method by receiver operating characteristic analysis) and distribution-based approaches (effect size calculations) were utilized to determine the magnitude of minimal clinically important difference. Results. According to our results, any improvements larger than -3.44 points or worsening larger than 2.07 points can represent clinically important changes for the patients. These thresholds have the effect size of 0.21 and -0.21, respectively. Conclusions. Minimal clinically important differences are the smallest change of scores that are subjectively meaningful to patients. Studies using the PDSS-2 as outcome measure should utilize the threshold of -3.44 points for detecting improvement or the threshold of 2.07 points for observing worsening. PMID- 26539304 TI - Quality Assessment of Ojeok-San, a Traditional Herbal Formula, Using High Performance Liquid Chromatography Combined with Chemometric Analysis. AB - Ojeok-san (OJS) is a traditional herbal formula consisting of 17 herbal medicines that has been used to treat various disorders. In this study, quantitative analytical methods were developed using high-performance liquid chromatography equipped with a photodiode array detector to determine 19 marker compounds in OJS preparations, which was then combined with chemometric analysis. The method developed was validated in terms of its precision and accuracy. The intra- and interday precision of the marker compounds were <3.0% of the relative standard deviation (RSD) and the recovery of the marker compounds was 92.74%-104.16% with RSD values <3.0%. The results of our quantitative analysis show that the quantities of the 19 marker compounds varied between a laboratory water extract and commercial OJS granules. The chemometric analysis used, principal component analysis (PCA) and hierarchical clustering analysis (HCA), also showed that the OJS water extract produced using a laboratory method clearly differed from the commercial OJS granules; therefore, an equalized production process is required for quality control of OJS preparations. Our results suggest that the HPLC analytical methods developed are suitable for the quantification and quality assessment of OJS preparations when combined with chemometric analysis involving PCA and HCA. PMID- 26539305 TI - Physicochemical Characteristics and Composition of Three Morphotypes of Cyperus esculentus Tubers and Tuber Oils. AB - Tuber characteristics and nutrient composition of three morphotypes of Cyperus esculentus tubers and tuber oils were determined. The mean value for length and width of the tuber and one thousand dried tuber weights ranged from 0.98 to 1.31 cm, 0.90 to 1.19 cm, and 598 to 1044 g, respectively. Tubers displayed high level of starch (30.54-33.21 g 100 g(-1)), lipid (24.91-28.94 g 100 g(-1)), and sucrose (17.98-20.39 g 100 g(-1)). The yellow tubers had significantly higher content in lipid compared to black ones. Levels of ascorbic acid, tocopherol, and beta carotene of the three morphotypes differed significantly. Yellow ones (morphotypes 1 and 2) were the richest in tocopherol and the poorest in beta carotene. Saturated fatty acid content of morphotype 2 was significantly lower than that of morphotypes 1 and 3. Morphotype 3 had the significantly lowest PUFA content compared to morphotypes 1 and 2. Morphotype 1 was found to be richer in Ca, Cu, and Mn contents. Al, Mg, P, S, and Si were most abundant in morphotype 2. Morphotype 3 had the highest content of Cl, K, and Zn. PMID- 26539306 TI - The Content of Secondary Metabolites and Antioxidant Activity of Wild Strawberry Fruit (Fragaria vesca L.). AB - Chemical analyses carried out in 2011-2013 aimed at evaluating the contents of flavonoids, free phenolic acids, tannins, anthocyanins, and antioxidant activity (%) by means of DPPH radical neutralization ability in fresh and air-dried fruits of three wild strawberry cultivars. Examinations revealed differences in contents of biologically active substances determined in raw versus dried material depending on the cultivar. Mean concentrations of flavonoids and tannins were highest in raw fruits of "Baron von Solemacher" cv., which amounted to 1.244 mg.g(-1) and 6.09%, respectively. Fresh fruits of "Regina" cv. were characterized by the highest average content of phenolic acids and anthocyanins: 4.987 mg.g(-1) and 0.636 mg.100 g(-1). The pattern of mean contents of biologically active substances analyzed in air-dried fruits was similar. Significant differences in abilities to neutralize the DPPH radical to diphenylpicrylhydrazine by extracts made of examined wild strawberry fruits were also indicated. PMID- 26539308 TI - Nonoperative management of craniovertebral junction and cutaneous tuberculosis. AB - BACKGROUND: Craniovertebral junction (CVJ) and cutaneous tuberculosis (TB) are both rare, each occurring in 0.3-1.0% of patients. To our knowledge, there are no existing cases reporting these manifestations of TB simultaneously. We report a case of TB involving the left CVJ as well as the skin, and discuss our management while providing a review of the literature. CASE DESCRIPTION: An adult patient was presented with progressive nocturnal neck pain associated with the development of several skin lesions. Investigations revealed multiple osseous lesions including the left CVJ. Biopsy of the CVJ lesion was unamenable due to proximity of the vertebral artery; therefore, the patient underwent biopsy of the other sites. Histological examination demonstrated features consistent with TB infection and the patient commenced 12 months of standard anti-TB therapy with cervical spine immobilization. At 2-month review, the patient was well with a near-complete resolution of neck pain and cutaneous lesions. Repeat imaging at 6 months follow-up demonstrated a stable C1 lesion with no evidence of instability. CONCLUSION: CVJ TB may be treated solely with anti-TB therapy and immobilization to good effect if there is no gross instability or neurological deficit. Similarly, cutaneous TB responds well to standard anti- TB therapy. Our experience suggests that co-existing tuberculous lesions in the CVJ and skin can be simultaneously managed with standard therapy without significant alterations to treatment regimes or prognosis. PMID- 26539307 TI - Multiple hemorrhagic intraparenchymal tumors presenting with fatal intracranial hypertension: A rare manifestation of systemic epithelioid hemangioendothelioma. AB - BACKGROUND: Epithelioid hemangioendotheliomas (EHE) is an extremely rare tumor that can arise not only intracranially but also systemically. Its radiological characteristics and the mechanism underlying the multiple organ involvement in EHE are poorly understood. CASE DESCRIPTION: A 24-year-old woman with a 7-month history of coughing and blood-stained sputum complained of visual disturbance in the right eye that had persisted for 1-month. Magnetic resonance (MR) imaging revealed multiple intraparenchymal masses with low-intensity on MR susceptibility weighted images with minimal enhancement with gadolinium. Systemic computed tomography revealed multiple nodules in both lungs and the liver. Because her neurological status rapidly deteriorated, brain biopsy of the right frontal mass was performed. The pathological diagnosis was EHE. Over the following 3 months, the patient gradually developed disturbance of consciousness. She died at 4 months after admission because of significant intracranial hypertension. CONCLUSION: Although intracranial EHEs are extremely rare, they should be included in the differential diagnoses of multiple small-sized masses with low intensity on MR susceptibility-weighted images. We also emphasize that the systemic involvement of this tumor was more compatible with multicentric development than metastasis. PMID- 26539310 TI - A fast cranial drilling technique in treating severe intracranial hemorrhage. AB - BACKGROUND: This study is a retrospective case analysis of 143 patients who suffered from severe intracranial hemorrhage and underwent a fast and simple procedure of cranial drilling followed with external ventricle drain treatment (referred as Fast-D here after) during 2003-2013 to evaluate the clinical effectiveness of the treatment. METHODS: Fast-D procedure was conducted on 143 patients with severe acute craniocerebral diseases. Those patients were evaluated using activities of daily living (ADL) scales at hospital discharge and after 6 month of physical therapy, and were compared to 36 patients with similar craniocerebral diseases but received the traditional Dandy's surgical treatment. RESULTS: At discharge, 11% (16 cases) was classified as ADL I (fully functional for physical and social activities); 26% (37 cases) had ADL II (fully functional for physical activities but partially impaired for social activities); 34% (49 cases) was ADL III (require assistance performing physical activities); 9% (13 cases) was ADL IV (being conscious, but completely lost ability of physical activities); 27% (10 cases) was ADL V (vegetative stage); and 13% (18 cased) was ADL VI (died) among the 143 patients. Six-month physical therapy improved ADL in 88% of the patients. Those outcomes are equal or better than the more complicated Dandy's procedure probably due to the time-saving factor. CONCLUSION: Fast-D procedure is much faster (6.7 min vs. 53.6 min of the Dandy's procedure) and can be performed outside operating rooms (computed tomography room or bedside). This technique could serve as a tool to rapidly release intracranial pressure and reduce subsequent morbidity and mortality of severe craniocerebral diseases when resource and condition are limited and more elaborate operating room procedures are not possible. PMID- 26539309 TI - Magnetic resonance imaging fluid-attenuated inversion recovery sequence signal reduction after endoscopic endonasal transcribiform total resection of olfactory groove meningiomas. AB - BACKGROUND: Olfactory groove meningiomas grow insidiously and compress adjacent cerebral structures. Achieving complete removal without further damage to frontal lobes can be difficult. Microsurgical removal of large lesions is a challenging procedure and usually involves some brain retraction. The endoscopic endonasal approaches (EEAs) for tumors arising from the anterior fossa have been well described; however, their effect on the adjacent brain tissue has not. Herein, the authors utilized the magnetic resonance imaging fluid attenuated inversion recovery (FLAIR) sequence signal as a marker for edema and gliosis on pre- and post-operative images of olfactory groove meningiomas, thus presenting an objective parameter for brain injury after surgical manipulation. METHODS: Imaging of 18 olfactory groove meningiomas removed through EEAs was reviewed. Tumor and pre/postoperative FLAIR signal volumes were assessed utilizing the DICOM image viewer OsiriX((r)). Inclusion criteria were: (1) No previous treatment; (2) EEA gross total removal; (3) no further treatment. RESULTS: There were 14 females and 4 males; the average age was 53.8 years (+/-8.85 years). Average tumor volume was 24.75 cm(3) (+/-23.26 cm(3), range 2.8-75.7 cm(3)), average preoperative FLAIR volume 31.17 cm(3) (+/-39.38 cm(3), range 0-127.5 cm(3)) and average postoperative change volume, 4.16 cm(3) (+/-6.18 cm(3), range 0-22.2 cm(3)). Average time of postoperative scanning was 6 months (range 0.14-20 months). In all cases (100%) gross total tumor removal was achieved. Nine patients (50%) had no postoperative FLAIR changes. In 2 patients (9%) there was minimal increase of changes postoperatively (2.2 cm(3) and 6 cm(3) respectively); all others demonstrated image improvement. The most common complication was postoperative cerebrospinal fluid leakage (27.8%); 1 patient (5.5%) died due to systemic complications and pulmonary sepsis. CONCLUSIONS: FLAIR signal changes tend to resolve after endonasal tumor resection and do not seem to worsen with this operative technique. PMID- 26539311 TI - Primary central nervous system vasculitis preceded by granulomatous hypophysitis: Case report with a review of the literature. AB - BACKGROUND: Primary central nervous system (CNS) vasculitis is an idiopathic inflammatory process that selectively affects CNS vasculature without a systemic inflammatory response, and causes luminal obstruction with resultant ischemia of recipient tissue. Its varying clinical symptoms and signs depend on the caliber of vessels involved and distribution and location of the affected structures. Granulomatous hypophysitis (GH) is an autoimmune inflammatory process typically affecting women, and usually presents with hypopituitarism, and at times, diabetes insipidus, and/or visual loss. Both entities are rare CNS diseases, which, to our knowledge, have never been previously reported in the same patient. CASE DESCRIPTION: We present a unique case of chronic progressive primary CNS vasculitis causing limbic encephalopathy in a 30-year-old male with only a history of medication-controlled hypertension. He initially presented 4 months prior with nonspecific neurological complaints and was found to have a homogenously enhancing and enlarged pituitary, which was biopsy proven to be GH. CONCLUSION: This rather unique presentation highlights the need to maintain a high index of suspicion for underlying PCNS vasculitis in a patient who does not fit the typical demographic for isolated GH. PMID- 26539312 TI - An aneurysm at the site of the fenestration of the middle cerebral artery in a patient with multiple aneurysms: A case report. AB - BACKGROUND: Middle cerebral artery (MCA) fenestration is a very rare anatomical variant of the MCA, incidentally found during magnetic resonance or computed tomography angiography. It has an incidence of 0.6%. Unlike fenestration of the posterior cerebral arterial circulation, fenestration of the anterior cerebral arterial circulation has not been well described. METHODS: We present the rare case of a patient who was admitted for a ruptured aneurysm of the MCA arising at the site of the fenestration of the MCA and also an unruptured fusiform aneurysm of the right posterior communicating artery and a distal anterior cerebral artery (ACA) aneurysm. RESULTS: The patient underwent craniotomy with microsurgical aneurysm clipping and the previously undiagnosed ruptured aneurysm, at the site of the fenestration of the MCA, arose immediately. Postoperatively, the patient awoke without a deficit. After treatment of postoperative bacterial meningitis, he was discharged on the 26(th) postoperative day in good condition without any neurologic deficit. Six months after the first surgery, he was operated for the distal azygos ACA aneurysm. CONCLUSION: Anomalies of the intracranial vasculature are common, and we describe a rare case of left MCA fenestration with an associated ruptured aneurysm at the site of the fenestration. In the literature, cases of fenestration of the MCA are sporadically reported and are only incidental findings. PMID- 26539313 TI - An unusual variant of the common trunk of the fronto-orbital and frontopolar arteries associated with a ruptured aneurysm of the A1 segment of the anterior cerebral artery. AB - BACKGROUND: The common trunk of the fronto-orbital artery (FOA) and frontopolar artery (FPA) arising from the A1 segment of the anterior cerebral artery (ACA) associated with a ruptured aneurysm (AN), is rare. CASE DESCRIPTION: The patient was a 52-year-old man who suffered from subarachnoid hemorrhage. Three dimensional computed tomography angiography revealed an elongated and tortuous left A1 segment of the ACA and a saccular AN arising from the left A1 segment of the ACA at the origin of the cortical branch, defining its location just on the midline and behind the anterior communicating artery. This vessel had two branches. One branch ran along the inferior surface of the ipsilateral frontal lobe, and the other branch ran anteriorly and medially along the surface of the left hemisphere toward the frontal pole. The anomalous artery was interpreted as a common trunk of the FOA and FPA. Bifrontal craniotomy was performed. The anomalous artery arose from the A1 segment of the ACA at the origin of the AN, and the recurrent artery of Heubner branched off the anomalous artery. The AN was successfully obliterated, clipping with a bayonet-shaped Yasargil titanium clip. Complete AN occlusion and patency of both the A1 and the common trunk of the FOA and FPA, were confirmed intraoperatively by indocyanine green angiography. CONCLUSIONS: Recognizing this variant preoperatively, could be helpful in preventing the complications of surgery. PMID- 26539314 TI - Accessory middle cerebral artery associated with an unruptured aneurysm at its origin. AB - BACKGROUND: An aneurysm originating from the junction of the A1 segment of the anterior cerebral artery and accessory middle cerebral artery (Acc-MCA) is markedly rare. We report a rare case of an Acc-MCA aneurysm, and discuss the clinical course and management of this rare condition. CASE DESCRIPTION: A 64 year-old man with a past history of cerebral infarction was revealed to have a left Acc-MCA and an aneurysm at its origin. The aneurysm was clipped via a transsylvian approach. Due to its location and projectile direction, the neck of the aneurysm was left partially unclipped. CONCLUSION: Although an Acc-MCA aneurysm is very rare, it has a potential risk of rupture. Therefore, radical treatment is necessary for such aneurysms. PMID- 26539315 TI - Ruptured spinal arteriovenous malformation: Presenting as stunned myocardium and neurogenic shock. AB - BACKGROUND: Neurogenic pulmonary edema (NPE) is a clinical syndrome usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. NPE was identified 100 years ago, but it is still underappreciated in the clinical setup. NPE usually appears within minutes to hours after the injury. It has a high mortality rate if not recognized early and treated appropriately. Similarly, neurogenic shock is a known complication of spinal cord injury reported incidence is more than 20% in isolated upper cervical spinal injury. But NPE is rare to occur, and stunned myocardium (SM) is not reported in spinal arteriovenous malformation (AVM) rupture. SM is a reversible cardiomyopathy resulting in transient left ventricular dysfunction which has been described to occur in the setting of catecholamine release during situations of physiologic stress. We report a case of high spinal AVM rupture presenting as SM, NPE, and neurogenic shock. CASE DESCRIPTION: A 32-year-old male who presented with sudden onset of pain and weakness in upper limbs. Imaging studies showed AVM rupture by imaging techniques. Initially, the patient had severe hypertension, respiratory distress requiring intubation and ventilation, then he developed hypotension, bradycardia, and asystole, which required immediate cardiopulmonary resuscitation and atropine. He remained with quadriplegia and suffered from frequent episodes of bradycardia and asystole. CONCLUSIONS: Spinal AVM rupture can present as neurogenic shock, stunned myocardium, and pulmonary edema. Early recognition of AVM rupture and prompt surgical intervention, as well as aggressive treatment of shock, may enhance recovery and decrease the long-term morbidity. PMID- 26539316 TI - Spinal dorsal dermal sinus tract: An experience of 21 cases. AB - BACKGROUND: Spinal dorsal dermal sinus is a rare entity, which usually comes to clinical attention by cutaneous abnormalities, neurologic deficit, and/or infection. The present study was undertaken to know the clinical profile of these patients, to study associated anomalies and to assess the results of surgical intervention. METHODS: Medical records of 21 patients treated for spinal dorsal dermal sinus from September 2007 to December 2013 were reviewed. RESULTS: We had 21 patients with male: female ratio of 13:8. Only 2 patients were below 1-year of age, and most cases (15) were between 2 and 15 years (mean age = 8.2 years). Lumbar region (11 cases) was most frequently involved, followed by thoracic (4 cases), lumbosacral, and cervical region in 3 patients each. All of our patients presented with neurological deficits. Three patients were admitted with acute meningitis with acute onset paraplegia and had intraspinal abscess. The motor, sensory, and autonomic deficits were seen in 14, 6, and 8 patients, respectively. Scoliosis and congenital talipes equinovarus were the common associated anomalies. All patients underwent surgical exploration and repair of dysraphic state and excision of the sinus. Overall, 20 patients improved or neurological status stabilized and only 1 patient deteriorated. Postoperative wound infection was seen in 2 cases. CONCLUSIONS: All patients with spinal dorsal dermal sinuses should be offered aggressive surgical treatment in the form of total excision of sinus tract and correction of spinal malformation, as soon as diagnosed. PMID- 26539317 TI - Eosinophilic granuloma/Langerhans cell histiocytosis: Pediatric neurosurgery update. PMID- 26539318 TI - Neurofibromatosis type 2 patient presenting with medulloblastoma. AB - BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas. CASE DESCRIPTION: We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and paternal uncle. Magnetic resonance imaging brain revealed a solid enhancing lesion arising from the right cerebellar cortex, which was effacing the fourth ventricles and causing hydrocephalus. Craniotomy and excision of the lesion were performed. Histopathology report confirmed the diagnosis to be desmoplastic medulloblastoma. Based on the patients' subsequent history and family history, he was diagnosed to be a case of NF2. CONCLUSION: This is the first case of medulloblastoma occurring in a patient with NF2 and raises the possibility of an association between medulloblastoma and NF2. PMID- 26539319 TI - Spontaneous Meckel's cave hematoma: A rare cause of trigeminal neuralgia. AB - BACKGROUND: The most common etiology of classic trigeminal neuralgia (TN) is vascular compression. However, other causes must be considered. Among these, spontaneous hematoma of the Meckel's cave (MC) causing symptomatic TN is very rare. CASE DESCRIPTION: We present the case of a 60-year-old woman with a 2-month history of left TN and diplopia. Neuroradiological examinations revealed a well defined hematoma in the left MC. The patient underwent surgical decompression with a progressive neurological improvement. CONCLUSION: Despite the number of lesions potentially affecting the MC, spontaneous hemorrhage is rare but should be taken into account in the differential diagnosis. PMID- 26539320 TI - Papillary tumor of the pineal region with extended clinical and radiologic follow up. AB - BACKGROUND: Papillary tumor of the pineal region (PTPR) is a rare neoplasm with only anecdotal data to guide the treatment. Results of treatment with surgery, radiation therapy, and chemotherapy have been reported to have varying degrees of success. Here we report a patient with a PTPR, who underwent subtotal resection, gamma knife stereotactic radiosurgery, and adjuvant temozolomide chemotherapy. CASE DESCRIPTION: During 9 years of clinical and radiographic follow-up, the patient has had regression of residual tumor and remains asymptomatic. CONCLUSION: When gross total resection of a PTPR is not possible, treatment with gamma knife stereotactic radiosurgery and temozolomide chemotherapy may provide long-term tumor control. PMID- 26539321 TI - Co-presentation of a subdural empyema and an infected ventriculoperitoneal shunt in an adult patient: A rare complication with review of literature. AB - BACKGROUND: The occurrence of a subdural empyema as a complication of a ventriculoperitoneal (VP) shunt infection is rare. Only three articles have been published on this topic. Moreover, the available literature only involves pediatric patients. CASE DESCRIPTION: The authors present a 38-year-old male with a preexisting right frontal subdural hygroma that developed into a subdural empyema in the presence of an infected right occipital VP shunt. A brief literature review is provided, and the pathogenesis is discussed. CONCLUSION: This is the first known report regarding an adult patient with a subdural empyema and a VP shunt infection. Although a magnetic resonance imaging (MRI) brain is not typically ordered during diagnosis of a shunt infection, the authors advocate a low threshold to employ MRI brain to evaluate for other sources of infection, especially in an immunocompromised patient or in a patient with a history of a subdural hematoma or hygroma that can be easily overlook as being stable on computed tomography of head. PMID- 26539322 TI - Granulomatous amebic encephalitis following hematopoietic stem cell transplantation. AB - BACKGROUND: Granulomatous amebic encephalitis (GAE) is rare, but often fatal. The infection has been documented predominantly among the immunocompromised population or among those with chronic disease. To date, however, there have only been eight cases regarding the infection following hematopoietic stem cell transplantation (HSCT). CASE DESCRIPTION: A 62-year-old female with a history of relapsed diffuse large B-cell lymphoma, recently underwent peripheral blood autologous stem cell transplant after BEAM conditioning (day 0). On day +15, she began to exhibit worsening fatigue, generalized weakness, and fever. Symptoms progressed to nausea, emesis, somnolence, confusion, and frontal headaches over the next few days. Imaging demonstrated multifocal ill-defined vasogenic edema with patchy enhancement. The patient was started on broad antibiotics, antifungals, and seizure prophylaxis. Evaluation for bacterial, fungal, mycobacterial, and viral etiologies was fruitless. Her mental status progressively deteriorated. On day +22, she exhibited severe lethargy and went into pulseless electrical activity arrest, requiring chest compressions. The episode lasted <2 min and her pulse was restored. She was taken to the operating room for a brain biopsy. Postoperatively, her right pupil began to dilate compared to the left; she demonstrated extensor posturing in her upper extremities and withdrawal in her lower extremities. Repeat computed tomography demonstrated progressive edema. Given poor prognosis and poor neurological examination, the family opted for withdrawal of care. Final pathology was consistent with Acanthamoeba GAE. CONCLUSION: The authors report the third case of GAE after autologous stem cell transplant, and the ninth case overall after HSCT. This case is unusual due to its rapid clinical presentation after HSCT compared to prior literature. The case highlights the need for high suspicion of Acanthamoeba infection in this patient population. PMID- 26539323 TI - Pharmacokinetics of monoclonal antibodies used for inflammatory bowel diseases in pregnant women. AB - Inflammatory bowel disease (IBD) is a condition of chronic immune response and inflammation of the gastrointestinal tract. Most women with IBD are affected during their reproductive years, and untreated IBD can have detrimental maternal and fetal outcomes. In recent years, many biological therapies including anti-TNF agents (infliximab, adalimumab, and certolizumab) have been developed for the treatment of IBD. An increasing number of IBD patients are treated with these agents during pregnancy. Sporadic reports suggest an absence of negative pregnancy outcomes related to use of anti-TNF agents in women with IBD. However, it is unclear if the physiological changes occurring in pregnancy alter mAb dose requirements for optimal maternal disease management and minimal fetal exposure to therapeutic antibodies. Based on current understanding of the pharmacokinetic profiles for anti-TNF agents in nonpregnant subjects, it appears very likely that physiological changes accompanying pregnancy can alter pharmacokinetics of anti TNF agents. This review focuses on how such physiological changes may impact disposition of anti-TNF agents during pregnancy. Further improvement in pregnancy outcomes may be achieved in women with IBD by better understanding of pregnancy mediated changes in the pharmacokinetics of anti-TNF agents. PMID- 26539324 TI - Treatment of Chronic Scapholunate Ligament Injury. PMID- 26539325 TI - Outcomes of Capitohamate Bone-Ligament-Bone Grafts for Scapholunate Injury. AB - Purpose In an attempt to restore natural carpal kinematics more closely, bone ligament-bone (BLB) grafts have been described for treating scapholunate (SL) injury. In this article we report the long-term results of capitohamate BLB autograft for the treatment of SL dissociation. Methods The medical records of patients treated with capitohamate BLB grafts for SL dissociation were retrospectively reviewed. Twenty-three patients were available for evaluation. Patients were sent a Disabilities of the Arm, Shoulder, and Hand (DASH) and a Patient-Rated Wrist Evaluation (PRWE) questionnaire and returned for exam. Thirteen patients returned the questionnaire, and 12 wrists were examined. Range of motion, grip strength, pain, complications, return to work, and radiographic parameters were documented. Results The average length of follow-up evaluation was 9.2 years. The average SL gap was 4.5 mm preoperatively and 3.6 mm at final follow-up. The average SL angle was 70 degrees preoperatively and 73 degrees at final follow-up. There was no statistically significant difference in preoperative versus postoperative flexion, extension, radial deviation, ulnar deviation, or grip strength. The average postoperative visual analog scale (VAS) score was 1.25 at rest and 3.58 with activity. The average Mayo Wrist Score was 66.8 preoperatively and 70.9 postoperatively (p = 0.158). The average postoperative PRWE was 20.5, and average postoperative DASH was 15.1. At final follow-up, four patients had no radiographic evidence of arthritis. Two patients had evidence of early-stage radiocarpal arthritis, four had evidence of midcarpal arthritis, and two had radiographic evidence of mild scaphotrapeziotrapezoid arthritis. One patient required a salvage procedure with four-corner fusion. Discussion BLB reconstruction can be used to treat SL instability. At final follow-up, the majority of patients did not worsen clinically or functionally or require secondary salvage procedures; however, radiologic progression of arthritis was not prevented. These outcomes are comparable to midterm results of other SL reconstructive options; thus, we have abandoned this technique for other less technically demanding procedures. Level of Evidence IV. PMID- 26539326 TI - A New Technique for Volar Capsulodesis for Isolated Palmar Scapholunate Interosseous Ligament Injuries: A Cadaveric Study and Case Report. AB - Introduction Most surgical techniques for scapholunate interosseous ligament (SLIL) repair address only the dorsal component of the ligament, potentially leading to high surgical failure rates. We introduce a new technique to reconstruct the volar SLIL using a portion of the long radiolunate ligament (LRL). A biomechanical evaluation was performed to evaluate the rupture strength of this repair, and a subsequent anatomic study was performed to verify that this repair would not compromise the blood supply to either the scaphoid or the lunate. Methods A reconstruction of the volar SLIL was developed utilizing a lunate-based strip of the LRL. Fourteen cadaver arms were injected with red colored epoxide and latex. The blood supply of the volar wrist capsule was dissected. The vascular supply to the ligaments, scaphoid, and lunate were investigated. The biomechanical strength of this reconstruction was tested on five cadaver arms by potting the scaphoid, lunate, and radius and subjecting the repair to a tensile load using a servohydraulic vertical displacement testing machine. Results In all arms, a branch of the radial artery or radiocarpal arch supplied the radioscapholunate ligament at the medial border of the LRL. The proximal half of the scaphoid was supplied by dorsal branches of the radial artery. In all cases, a vessel entered the lunate on its ulnar volar side, away from the repair. The average strength of the intact LRL strip was 97.4 N, and the average strength of the ligament-suture interface used for the capsulodesis was 43.5 N. Conclusion This volar approach to the SLIL does not compromise the vascularity of the scaphoid or the lunate. This approach allows the possibility of repairing or augmenting the volar SLIL. The strength of this repair appears to be less than the strength of the native SLIL. Further clinical studies are warranted. PMID- 26539327 TI - Reconstruction of the Scapholunate Ligament Using Capitohamate Bone-Ligament Bone. AB - Background The biomechanical properties of the capitohamate (CH) ligament are equivalent to those of the scapholunate (SL) interosseous ligament. We reconstructed the SL ligament using the CH bone-ligament-bone substitute for chronic injury of the SL ligament. Patients and Methods Beginning in 2008, 15 wrists of 14 patients with an average age of 38 years underwent this procedure with a minimum follow-up of 2 years. Thirteen wrists had an SL joint gap more than 3 mm, and two had a complete SL ligament disruption with a severe dorsal intercalated segment instability (DISI) deformity. Kirschner wires (K-wires) were removed 8 weeks after the surgery, then active ROM exercise began. Pain (on visual analog scale [VAS]), wrist motion (angle), radiographic characteristics, such as SL gap (mm) and SL angle, and Modified Mayo Wrist Score (MMWS) were evaluated. Technique The SL joint was reduced by manipulation or with the use of joysticks, then temporary fixed with K-wires. A dorsal trough was then made between the scaphoid and the lunate. The proximal half of the CH ligament was harvested with attached bone from the capitate and hamate (CH bone-ligament bone), inset into the SL trough, and fixed firmly with 1.2-mm diameter titanium screws in the scaphoid and lunate, respectively. Results The VAS improved from 77 preoperatively to 12 postoperatively. The average wrist extension/flexion was 74 degrees /60 degrees . There was no ossification of the reconstructed SL at the final follow-up. The SL gap improved from an average of 4.8 mm to an average of 2.1 mm, and the SL angle changed from 67 degrees to 55 degrees . The MMWS improved to 82 points postoperatively from a preoperative average of 47 with eight excellent, five good, and two fair results. PMID- 26539328 TI - Combined Treatment of Wrist and Trapeziometacarpal Joint Arthritis. AB - Background Combined thumb basal and wrist joint arthritis (excluding scaphotrapeziotrapezoid arthritis) is rare considering the frequency of arthritis of either joint alone. Combined surgical treatment has never been described in the literature. Furthermore, the scaphoidectomy common to all interventions for Watson stage 2 or 3 wrist arthritis theoretically makes it impossible to perform a trapeziectomy for thumb basal joint arthritis. Question/Purpose The aim of this study was to present and analyze the results of two types of surgical treatment when both wrist and thumb arthritis was present. Materials and Methods Our retrospective series included 11 patients suffering from Eaton Stage III thumb basal joint arthritis and scapholunate advanced collapse (SLAC) II and III-type wrist arthritis. Five patients (group A) underwent trapeziectomy and palliative surgery for their wrist with conservation of the distal pole of the scaphoid (one proximal row carpectomy [PRC] and four four-corner fusions), and six (group B) patients had a trapeziometacarpal arthroplasty either with PRC (two cases) or four-corner arthrodesis (four cases) including total scaphoidectomy. Results The mean follow-up was 57 months. The overall visual analog scale (VAS) score for pain was 1.5 at rest, with no difference between the trapeziectomy and arthroplasty groups. The average Kapandji score was 9.3 (9 in group A and 9.5 in group B). The flexion/extension range of motion for the wrist was 64 degrees following four-corner arthrodesis and 75 degrees following PRC. Only one case of algodystrophy was observed. The radiological analysis revealed no complications. Discussion This study shows that thumb basal joint arthritis and SLAC type wrist arthritis may be treated by combined treatment during the same intervention without any complications. The results of palliative surgery for the wrist, either with trapeziectomy or with a trapeziometacarpal arthroplasty, are comparable. With a trapeziectomy, the distal pole of the scaphoid must be fused to the capitate to help stabilize the thumb column. Level of Evidence Level IV. PMID- 26539329 TI - Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism. AB - Anxiety disorders (ADs) are disabling chronic disorders with exaggerated behavioral response to threats. This study was aimed at testing the hypothesis that ADs may be associated with reduced neurotrophic activity, particularly of Brain-derived neurotrophic factor (BDNF), and determining possible effects of genetics on serum BDNF concentrations. In 672 adult subjects from six isolated villages in North-Eastern Italy with high inbreeding, we determined serum BDNF levels and identified subjects with different ADs subtypes such as Social and Specific Phobias (PHSOC, PHSP), Generalized Anxiety Disorder (GAD), and Panic Disorder (PAD). Analysis of the population as a whole or individual village showed no significant correlation between serum BDNF levels and Val66Met polymorphism and no association with anxiety levels. Stratification of subjects highlighted a significant decrease in serum BDNF in females with GAD and males with PHSP. This study indicates low heritability and absence of any impact of the Val66Met polymorphism on circulating concentrations of BDNF. Our results show that BDNF is not a general biomarker of anxiety but serum BDNF levels correlate in a gender-specific manner with ADs subtypes. PMID- 26539330 TI - An investigation of the genus Mesacanthus (Chordata: Acanthodii) from the Orcadian Basin and Midland Valley areas of Northern and Central Scotland using traditional morphometrics. AB - Mesacanthus is a common and speciose genus of acanthodian fish from Lower Old Red Sandstone and Middle Old Red Sandstone assemblages (representing the Lower Devonian and Middle Devonian respectively) and is well represented in many palaeoichthyology collections in the UK. Based upon descriptions given during the 19th century, specimens of the genus Mesacanthus from the Orcadian Basin and Midland Valley areas of Northern and Central Scotland have historically been referred to a number of different species; of these, the most frequently discussed in the literature are M. mitchelli, M. peachi and M. pusillus. In order to test the validity of these three species, traditional morphometric analyses were carried out on over 100 specimens of Mesacanthus, from both the Lower Devonian and the Middle Devonian, that cover the full range of known localities for these taxa in Northern and Central Scotland. Based upon morphological and morphometric comparisons, this investigation has found that at least two species of Mesacanthus are valid (M. mitchelli and M. pusillus) as specimens from the Lower Devonian and Middle Devonian have been shown to differ significantly in a number of important ways. However, no evidence has been found for the validity of the second and distinct Middle Devonian species, M. peachi. PMID- 26539331 TI - Effects of the acanthocephalan Polymorphus minutus and the microsporidian Dictyocoela duebenum on energy reserves and stress response of cadmium exposed Gammarus fossarum. AB - Amphipods are commonly parasitized by acanthocephalans and microsporidians and co infections are found frequently. Both groups of parasites are known to have severe effects on their host. For example, microsporidians can modify host sex ratio and acanthocephalans can manipulate the behavior of the amphipod to promote transmission to the final host. These effects influence host metabolism in general and will also affect the ability of amphipods to cope with additional stressors such as environmental pollution, e.g., by toxic metals. Here we tested the effects of sub-lethal concentrations of cadmium on glycogen and lipid levels, as well as on the 70kDa heat shock protein (hsp70) response of field collected Gammarus fossarum, which were naturally infected with microsporidians and the acanthocephalan Polymorphus minutus. Infected and uninfected G. fossarum were exposed to a nominal Cd concentration of 4 ug/L, which resembled measured aqueous Cd concentration of 2.9 ug/L in reconstituted water for 7 d at 15 degrees C in parallel to an unexposed control. After exposure gammarids were snap frozen, weighed, sexed and tested for microsporidian infection by PCR. Only individuals containing the microsporidian Dictyocoela duebenum were used for the further biochemical and metal analyses. P. minutus infected amphipods were significantly smaller than their uninfected conspecifics. Mortality was insignificantly increased due to cadmium exposure, but not due to parasite infection. Microsporidian infection in combination with cadmium exposure led to increased glycogen levels in female gammarids. An increase of glycogen was also found due to interaction of acanthocephalan and microsporidian infection. Elevated lipid levels were observed in all groups infected with microsporidians, while acanthocephalans had the opposite effect. A positive correlation of lipid and glycogen levels was observed. The general stress response measured in form of hsp70 was significantly increased in microsporidian infected gammarids exposed to cadmium. P. minutus did not affect the stress response of its host. Lipid levels were correlated negatively with hsp70 response, and indicated a possible increased stress susceptibility of individuals with depleted energy reserves. The results of our study clearly demonstrate the importance of parasitic infections, especially of microsporidians, for ecotoxicological research. PMID- 26539332 TI - Overexpression of IFITM3 predicts the high risk of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy. AB - Background. Recent studies have shown that the aberrant expression of IFITM3 is implicated in the lymph node metastasis of many malignancies. Our research aimed to investigate the expression of IFITM3 in pathological N0 (pN0) esophageal squamous cell carcinoma (ESCC) and its relationship with lymph node metastatic recurrence. Methods. Immunohistochemistry (IHC) was used to examine the expression profile of IFITM3 in 104 pairs of samples. Each pair consisted of ESCC tissue and its adjacent normal mucosa (ANM). This aberrant expression was verified by reverse transcription-polymerase chain reaction (RT-PCR) with 20 tumor specimens with strong immunostaining and their mucosal tissues. In addition, 20 samples of low expression tissues and their ANMs were evaluated. Moreover, the correlations between the IFITM3 expression level and the clinicopathological variables, recurrence risk and overall survival (OS) of patients were analyzed. Results. Both IHC and RT-PCR demonstrated that the IFITM3 expression level was significantly higher in tumor tissue than in ANM. Statistical analysis showed a significant correlation of IFITM3 expression with the T status of esophageal cancer (p = 0.015). In addition, IFITM3 overexpression was demonstrated to be not only an important risk factor of lymphatic metastatic recurrence but a significant prognostic factor in pN0 ESCC (p < 0.005). Conclusions. Even pN0 ESCC patients will still experience lymphatic metastatic recurrence. The IFITM3 gene could be a predictor of lymphatic metastatic recurrence in pN0 ESCC after Ivor-Lewis esophagectomy. PMID- 26539333 TI - Getting the most out of RNA-seq data analysis. AB - Background. A common research goal in transcriptome projects is to find genes that are differentially expressed in different phenotype classes. Biologists might wish to validate such gene candidates experimentally, or use them for downstream systems biology analysis. Producing a coherent differential gene expression analysis from RNA-seq count data requires an understanding of how numerous sources of variation such as the replicate size, the hypothesized biological effect size, and the specific method for making differential expression calls interact. We believe an explicit demonstration of such interactions in real RNA-seq data sets is of practical interest to biologists. Results. Using two large public RNA-seq data sets-one representing strong, and another mild, biological effect size-we simulated different replicate size scenarios, and tested the performance of several commonly-used methods for calling differentially expressed genes in each of them. We found that, when biological effect size was mild, RNA-seq experiments should focus on experimental validation of differentially expressed gene candidates. Importantly, at least triplicates must be used, and the differentially expressed genes should be called using methods with high positive predictive value (PPV), such as NOISeq or GFOLD. In contrast, when biological effect size was strong, differentially expressed genes mined from unreplicated experiments using NOISeq, ASC and GFOLD had between 30 to 50% mean PPV, an increase of more than 30-fold compared to the cases of mild biological effect size. Among methods with good PPV performance, having triplicates or more substantially improved mean PPV to over 90% for GFOLD, 60% for DESeq2, 50% for NOISeq, and 30% for edgeR. At a replicate size of six, we found DESeq2 and edgeR to be reasonable methods for calling differentially expressed genes at systems level analysis, as their PPV and sensitivity trade-off were superior to the other methods'. Conclusion. When biological effect size is weak, systems level investigation is not possible using RNAseq data, and no meaningful result can be obtained in unreplicated experiments. Nonetheless, NOISeq or GFOLD may yield limited numbers of gene candidates with good validation potential, when triplicates or more are available. When biological effect size is strong, NOISeq and GFOLD are effective tools for detecting differentially expressed genes in unreplicated RNA-seq experiments for qPCR validation. When triplicates or more are available, GFOLD is a sharp tool for identifying high confidence differentially expressed genes for targeted qPCR validation; for downstream systems level analysis, combined results from DESeq2 and edgeR are useful. PMID- 26539334 TI - Genetic models reveal historical patterns of sea lamprey population fluctuations within Lake Champlain. AB - The origin of sea lamprey (Petromyzon marinus) in Lake Champlain has been heavily debated over the past decade. Given the lack of historical documentation, two competing hypotheses have emerged in the literature. First, it has been argued that the relatively recent population size increase and concomitant rise in wounding rates on prey populations are indicative of an invasive population that entered the lake through the Champlain Canal. Second, recent genetic evidence suggests a post-glacial colonization at the end of the Pleistocene, approximately 11,000 years ago. One limitation to resolving the origin of sea lamprey in Lake Champlain is a lack of historical and current measures of population size. In this study, the issue of population size was explicitly addressed using nuclear (nDNA) and mitochondrial DNA (mtDNA) markers to estimate historical demography with genetic models. Haplotype network analysis, mismatch analysis, and summary statistics based on mtDNA noncoding sequences for NCI (479 bp) and NCII (173 bp) all indicate a recent population expansion. Coalescent models based on mtDNA and nDNA identified two potential demographic events: a population decline followed by a very recent population expansion. The decline in effective population size may correlate with land-use and fishing pressure changes post-European settlement, while the recent expansion may be associated with the implementation of the salmonid stocking program in the 1970s. These results are most consistent with the hypothesis that sea lamprey are native to Lake Champlain; however, the credibility intervals around parameter estimates demonstrate that there is uncertainty regarding the magnitude and timing of past demographic events. PMID- 26539335 TI - The association between negative attention biases and symptoms of depression in a community sample of adolescents. AB - Adolescence is a vulnerable time for the onset of depression. Recent evidence from adult studies suggests not only that negative attention biases are correlated with symptoms of depression, but that reducing negative attention biases through training can in turn reduce symptomology. The role and plasticity of attention biases in adolescent depression, however, remains unclear. This study examines the association between symptoms of depression and attention biases, and whether such biases are modifiable, in a community sample of adolescents. We report data from 105 adolescents aged 13-17 who completed a dot probe measure of attention bias before and after a single session of visual search-based cognitive bias modification training. This is the first study to find a significant association between negative attention biases and increased symptoms of depression in a community sample of adolescents. Contrary to expectations, we were unable to manipulate attention biases using a previously successful cognitive bias modification task. There were no significant effects of the training on positive affect and only modest effects of the training, identified in post-hoc analyses, were observed on negative affect. Our data replicate those from the adult literature, which suggest that adolescent depression is a disorder associated with negative attention biases, although we were unable to modify attention biases in our study. We identify numerous parameters of our methodology which may explain these null training effects, and which could be addressed in future cognitive bias modification studies of adolescent depression. PMID- 26539336 TI - Biotransformation of Momordica charantia fresh juice by Lactobacillus plantarum BET003 and its putative anti-diabetic potential. AB - Lactobacillus plantarum BET003 isolated from Momordica charantia fruit was used to ferment its juice. Momordica charantia fresh juice was able to support good growth of the lactic acid bacterium. High growth rate and cell viability were obtained without further nutrient supplementation. In stirred tank reactor batch fermentation, agitation rate showed significant effect on specific growth rate of the bacterium in the fruit juice. After the fermentation, initially abundant momordicoside 23-O-beta-Allopyranosyle-cucurbita-5,24-dien 7alpha,3beta,22(R),23(S)-tetraol-3-O-beta-allopyranoside was transformed into its corresponding aglycone in addition to the emergence of new metabolites. The fermented M. charantia juice consistently reduced glucose production by 27.2%, 14.5%, 17.1% and 19.2% at 15-minute intervals respectively, when compared against the negative control. This putative anti-diabetic activity can be attributed to the increase in availability and concentration of aglycones as well as other phenolic compounds resulting from degradation of glycosidic momordicoside. Biotransformation of M. charantia fruit juice via lactic acid bacterium fermentation reduced its bitterness, reduced its sugar content, produced aglycones and other metabolites as well as improved its inhibition of alpha glucosidase activity compared with the fresh, non-fermented juice. PMID- 26539337 TI - Two different approaches to the affective profiles model: median splits (variable oriented) and cluster analysis (person-oriented). AB - Background. The notion of the affective system as being composed of two dimensions led Archer and colleagues to the development of the affective profiles model. The model consists of four different profiles based on combinations of individuals' experience of high/low positive and negative affect: self fulfilling, low affective, high affective, and self-destructive. During the past 10 years, an increasing number of studies have used this person-centered model as the backdrop for the investigation of between and within individual differences in ill-being and well-being. The most common approach to this profiling is by dividing individuals' scores of self-reported affect using the median of the population as reference for high/low splits. However, scores just-above and just below the median might become high and low by arbitrariness, not by reality. Thus, it is plausible to criticize the validity of this variable-oriented approach. Our aim was to compare the median splits approach with a person oriented approach, namely, cluster analysis. Method. The participants (N = 2, 225) were recruited through Amazons' Mechanical Turk and asked to self-report affect using the Positive Affect Negative Affect Schedule. We compared the profiles' homogeneity and Silhouette coefficients to discern differences in homogeneity and heterogeneity between approaches. We also conducted exact cell wise analyses matching the profiles from both approaches and matching profiles and gender to investigate profiling agreement with respect to affectivity levels and affectivity and gender. All analyses were conducted using the ROPstat software. Results. The cluster approach (weighted average of cluster homogeneity coefficients = 0.62, Silhouette coefficients = 0.68) generated profiles with greater homogeneity and more distinctive from each other compared to the median splits approach (weighted average of cluster homogeneity coefficients = 0.75, Silhouette coefficients = 0.59). Most of the participants (n = 1,736, 78.0%) were allocated to the same profile (Rand Index = .83), however, 489 (21.98%) were allocated to different profiles depending on the approach. Both approaches allocated females and males similarly in three of the four profiles. Only the cluster analysis approach classified men significantly more often than chance to a self-fulfilling profile (type) and females less often than chance to this very same profile (antitype). Conclusions. Although the question whether one approach is more appropriate than the other is still without answer, the cluster method allocated individuals to profiles that are more in accordance with the conceptual basis of the model and also to expected gender differences. More importantly, regardless of the approach, our findings suggest that the model mirrors a complex and dynamic adaptive system. PMID- 26539338 TI - Partnering With Patients in the Development and Lifecycle of Medicines: A Call for Action. AB - The purpose of medicines is to improve patients' lives. Stakeholders involved in the development and lifecycle management of medicines agree that more effective patient involvement is needed to ensure that patient needs and priorities are identified and met. Despite the increasing number and scope of patient involvement initiatives, there is no accepted master framework for systematic patient involvement in industry-led medicines research and development, regulatory review, or market access decisions. Patient engagement is very productive in some indications, but inconsistent and fragmentary on a broader level. This often results in inefficient drug development, increasing evidence requirements, lack of patient-centered outcomes that address unmet medical needs and facilitate adherence, and consequently, lack of required therapeutic options and high costs to society and involved parties. Improved patient involvement can drive the development of innovative medicines that deliver more relevant and impactful patient outcomes and make medicine development faster, more efficient, and more productive. It can lead to better prioritization of early research; improved resource allocation; improved trial protocol designs that better reflect patient needs; and, by addressing potential barriers to patient participation, enhanced recruitment and retention. It may also improve trial conduct and lead to more focused, economically viable clinical trials. At launch and beyond, systematic patient involvement can also improve the ongoing benefit-risk assessment, ensure that public funds prioritize medicines of value to patients, and further the development of the medicine. Progress toward a universal framework for patient involvement requires a joint, precompetitive, and international approach by all stakeholders, working in true partnership to consolidate outputs from existing initiatives, identify gaps, and develop a comprehensive framework. It is essential that all stakeholders participate to drive adoption and implementation of the framework and to ensure that patients and their needs are embedded at the heart of medicines development and lifecycle management. PMID- 26539339 TI - A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders. AB - Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and followed across five years post-treatment to track DUI offense, motor vehicle-related offenses, and general criminal offenses. Psychiatric comorbidity, though it did not predict DUI recidivism specifically, predicted criminal re-offense more generally. In addition, there was a specific relationship between lifetime attention deficit disorder and repeated motor vehicle-related offenses. These findings suggest that for many repeat offenders, DUI is one outlet in a constellation of criminal behavior, and that psychiatric comorbidity increases vulnerability for criminal re-offense. PMID- 26539340 TI - Disability Prevalence According to a Class, Race, and Sex (CSR) Hypothesis. AB - Disability has been shown to be related in definite ways to social class. In modern industrial societies, disability is influenced by and has the potential to contribute to the production and reproduction of social inequality. However, markers of social stratification processes are sometimes ignored determinants of health. A Class, Race, Sex (CRS) hypothesis is presented to argue that a "low education disadvantage"; "racial-minority disadvantage"; and "female disadvantage" will compound to affect the risks for being disable. In particular, the CRS hypothesis posits that class is more important than race and the latter more than sex when predicting presence or severity of disability. The cross sectional study of community-dwelling adults between the ages of 45 and 64 uses data from the American Community Survey (ACS) Public Use Microdata Sample (PUMS) 2008-2012 file. By using 3,429,523 individuals-which weighted equal to 61,726,420 the results of the study suggest the CRS hypothesis applies to both Non-Latino Blacks and Non-Latino-Whites. There is a "male disadvantage" exception for Non Latino-Whites. Decreasing between-group differences in health may be achieved by making the age-health association at lower socioeconomic stratum similar to that of the upper socioeconomic strata. PMID- 26539341 TI - Extracting the Benefit of Nexrutine(r) for Cancer Prevention. AB - The current standard of care for prostate cancer includes hormone therapy, radiation therapy and radical prostatectomy, each with its own set of undesirable side effects. In this regard there is an unmet need to develop strategies that can prevent or delay the development of clinical prostate cancer. One potential area involves the use of natural compounds involving botanicals. Along these lines we have found that Nexrutine(r), a dietary supplement derived from Phellodendron amurense bark extract, has prostate cancer prevention activity. The "extract" nature of this botanical, which constitutes a blend of several active protoberberine alkaloids, allows it to target several pathways deregulated in prostate cancer simultaneously. In this review, we will emphasize the prospective translational benefit of Nexrutine(r) as a chemopreventive agent for prostate cancer management. The potential of Nexrutine(r) was first identified and has subsequently been most exhaustively studied with reference to prostate cancer. Therefore the focus of this review is on the use of Nexrutine(r) in prostate cancer. In addition we have summarized the emerging evidence regarding the use of Nexrutine(r) in other tumor models to demonstrate the potential benefits of Nexrutine(r). PMID- 26539343 TI - A meta-analysis of mitral valve repair versus replacement for ischemic mitral regurgitation. AB - BACKGROUND: The development of ischemic mitral regurgitation (IMR) portends a poor prognosis and is associated with adverse long-term outcomes. Although both mitral valve repair (MVr) and mitral valve replacement (MVR) have been performed in the surgical management of IMR, there remains uncertainty regarding the optimal approach. The aim of the present study was to meta-analyze these two procedures, with mortality as the primary endpoint. METHODS: Seven databases were systematically searched for studies reporting peri-operative or late mortality following MVr and MVR for IMR. Data were independently extracted by two reviewers and meta-analyzed according to pre-defined study selection criteria and clinical endpoints. RESULTS: Overall, 22 observational studies (n=3,815 patients) and one randomized controlled trial (n=251) were included. Meta-analysis demonstrated significantly reduced peri-operative mortality [relative risk (RR) 0.61; 95% confidence intervals (CI), 0.47-0.77; I(2)=0%; P<0.001] and late mortality (RR, 0.78; 95% CI, 0.67-0.92; I(2)=0%; P=0.002) following MVr. This finding was more pronounced in studies with longer follow-up beyond 3 years. At latest follow-up, recurrence of at least moderate mitral regurgitation (MR) was higher following MVr (RR, 5.21; 95% CI, 2.66-10.22; I(2)=46%; P<0.001) but the incidence of mitral valve re-operations were similar. CONCLUSIONS: In the present meta-analysis, MVr was associated with reduced peri-operative and late mortality compared to MVR, despite an increased recurrence of at least moderate MR at follow-up. However, these findings must be considered within the context of the differing patient characteristics that may affect allocation to MVr or MVR. Larger prospective studies are warranted to further compare long-term survival and freedom from re intervention. PMID- 26539342 TI - Retinoid Chemoprevention: Who Can Benefit? AB - Acute promyelocytic leukemia (APL) is a treatment success story. From a highly deadly disease it was turned into a highly curable disease by the introduction of differentiation-induction therapy with all-trans retinoic acid (ATRA) in the 1990's. During the last quarter of century, ATRA and other retinoids were used for the treatment and prevention of other cancers and even other diseases. The results were less spectacular, but nevertheless important. Progress has been made toward understanding the mechanism of action of retinoids in different physiological and pathological contexts. For some diseases, specific genetic backgrounds were found to confer responsiveness to retinoid therapy. Therapies that include retinoids and other modalities are very diverse and used both for combined targeting of multiple pathways and for diminishing toxicity. PMID- 26539344 TI - Repair or replace for severe ischemic mitral regurgitation: prospective randomized multicenter data. AB - Ischemic mitral regurgitation (IMR) is a subset of functional mitral regurgitation (MR) that has the potential to impact an increasing number of patients in the future. This is in the context of a worldwide population, which continues to live longer with improved survival after myocardial infarction. Substantial data have accumulated over the past few decades demonstrating the negative effects of IMR. Further, significant research has been done to define the optimal surgical approach and several studies have compared mitral repair versus replacement for patients with severe mitral regurgitation (SMR). Studies supporting performance of mitral repair cite superior operative morbidity and mortality rates, while proponents of mitral replacement cite improved long-term durability and correction of MR. Lack of clinically robust Level I randomized controlled trial data have curtailed attempts to better define appropriate surgical treatment allocation over the past few decades. Recently, however, the Cardiothoracic Surgical Trials Network (CTSN) conducted the first randomized controlled trial, funded by the National Heart, Lung, and Blood Institute, the National Institute for Neurological Diseases and Stroke and the Canadian Institute for Health Research, to compare the performance of mitral repair versus replacement for SMR. Herein, the present review describes the design, results and implications of the CTSN SMR trial and its efforts to identify the most efficacious surgical approach to SMR. This review also describes CTSN investigation to predict the recurrence of MR after mitral repair. PMID- 26539345 TI - Durability of mitral valve repair for mitral regurgitation due to degenerative mitral valve disease. AB - Degenerative diseases of the mitral valve (MV) are the most common cause of mitral regurgitation in the Western world and the most suitable pathology for MV repair. Several studies have shown excellent long-term durability of MV repair for degenerative diseases. The best follow-up results are obtained with isolated prolapse of the posterior leaflet, however even with isolated prolapse of the anterior leaflet or prolapse of both leaflets the results are gratifying, particularly in young patients. The freedom from reoperation on the MV at 15 years exceeds 90% for isolated prolapse of the posterior leaflet and it is around 70-85% for prolapse of the anterior leaflet or both leaflets. The degree of degenerative change in the MV also plays a role in durability of MV repair. Most studies have used freedom from reoperation to assess durability of the repair but some studies that examined valve function late after surgery suggest that recurrent mitral regurgitation is higher than estimated by freedom from reoperation. We can conclude that MV repair for degenerative mitral regurgitation is associated with low probability of reoperation for up to two decades after surgery. However, almost one-third of the patients develop recurrent moderate or severe mitral regurgitation suggesting that surgery does not arrest the degenerative process. PMID- 26539346 TI - Minimally invasive mitral valve repair through right minithoracotomy in the setting of degenerative mitral regurgitation: early outcomes and long-term follow up. AB - BACKGROUND: Mitral valve (MV) repair is the gold standard for the treatment of degenerative MV regurgitation. Recently, minimally invasive mitral valve surgery (MIMVS) has shown excellent postoperative outcomes compared with conventional surgery. The aim of our study is to report early and long-term outcomes of patients undergoing MIMVS through right mini-thoracotomy (RT) over an eight year period. METHODS: From September 2003 to December 2011, a total of 1,604 consecutive patients underwent MIMVS through RT. RESULTS: The mean age was 62+/ 13 years, 295 (42%) patients were female and 16 (2.3%) had previous cardiac operations. MV repair was successfully performed in 670 patients, with a rate of success of 95.3%. Repair techniques included annuloplasty (89%), leaflet resection (n=54.2%), neochordae implantation (12.1%), and sliding plasty (10.5%). Overall in-hospital mortality was 0.1%. Incidence of stroke was 1.3%. At eight year follow-up, overall survival was 90.1%, freedom from reoperation 93%, and freedom from recurrent mitral regurgitation was 90%. CONCLUSIONS: MIMV repair through right minithoracotomy is a safe and reproducible procedure associated with high rate of MV repair, and excellent early postoperative and long-term results. PMID- 26539347 TI - Long term outcomes of posterior leaflet folding valvuloplasty for mitral valve regurgitation. AB - BACKGROUND: Posterior mitral valve leaflet prolapse due to degenerative mitral valve disease has been treated with tissue sparing repair techniques since 2002. The simplified foldoplasty technique effectively lowers the height of the redundant posterior leaflet and creates an optimal coaptation line for the anterior leaflet that results in excellent long term durability, freedom from reoperation, and return of functional status. METHODS: Patient demographics and in-hospital outcome data were extracted from electronic medical records of 229 patients, aged 60.6+/-13.7 years who underwent the procedure for mitral valve repair (MVR) involving the posterior leaflet from myxomatous disease between 2002 and 2014. Parametric analyses were performed on outcomes data, while long-term survival was assessed by Kaplan-Meier analyses. RESULTS: Concomitant coronary bypass surgery was performed on 32/229 (14%) patients, the mean perfusion time was 119+/-40 min, and the mean cross clamp time was 86+/-31 min. Post-operative mortality was 2/229 (0.9%), reoperation for bleeding occurred in 4 (1.7%) and postoperative stroke in 4 (1.7%) patients. Long term follow up rate was 100% and the mean study follow-up duration was 6.8+/-2.3 years. Overall late mortality rate was 24/229 (14.9%), and mitral valve re-intervention was performed on 7 patients (4.3%). NYHA class III/IV and clinically significant MR at follow up were significantly lower compared to preoperative values (both P<0.001). CONCLUSIONS: Our results encourage further use of this simple and effective technique in patients with isolated posterior leaflet prolapse. PMID- 26539348 TI - Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective. AB - BACKGROUND: Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). METHODS: Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. RESULTS: Non-smoking men (<=65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. CONCLUSIONS: In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures. PMID- 26539349 TI - A novel approach to ischemic mitral regurgitation (IMR). AB - Ischemic mitral regurgitation (IMR) is a complicated medical condition with varying degrees of coronary artery disease and mitral regurgitation (MR). The traditional surgical treatment option for those with indications for intervention is coronary artery bypass grafting (CABG) plus or minus mitral valve repair or replacement (MVR). Percutaneous coronary intervention, hybrid coronary revascularization (HCR), and conventional CABG are three techniques available to address coronary artery disease (CAD). Percutaneous edge-to-edge repair, minimally invasive, and traditional sternotomy are accepted approaches for the treatment of MR. When taken in combination, there are nine methods available to revascularize the myocardium and restore competency to the mitral valve. While most of these treatment options have not been studied in detail, they may offer novel solutions to a widely variable and complex IMR patient population. Thus, a comparative analysis including an examination of potential benefits and risks will be helpful and potentially allow for more patient-specific treatment strategies. PMID- 26539350 TI - Standard transthoracic echocardiography and transesophageal echocardiography views of mitral pathology that every surgeon should know. AB - The mitral valve is the most commonly diseased heart valve and the prevalence of mitral valve disease increases proportionally with age. Echocardiography is the primary diagnostic imaging modality used in the assessment of patients with mitral valve disease. It is a noninvasive method which provides accurate anatomic and functional information regarding the mitral valve and can identify the mechanism of mitral valve pathology. This is especially useful as it may guide surgical repair. This is increasingly relevant given the growing trend of patients undergoing mitral valve repair. Collaboration between cardiac surgeons and echocardiographers is critical in the evaluation of mitral valve disease and for identification of complex valvular lesions that require advanced surgical skill to repair. This article will provide an overview of transthoracic and transesophageal assessment of common mitral valve pathology that aims to aid surgical decision making. PMID- 26539351 TI - 4D-transesophageal echocardiography and emerging imaging modalities for guiding mitral valve repair. PMID- 26539353 TI - Alternative approaches for mitral valve repair. AB - Unique situations arise in which alternative exposures for mitral valve surgery offer distinct advantages over traditional approaches. Each exposure facilitates both mitral valve repair and replacement, although the standard repair procedures must be modified to accommodate these non-traditional exposures. Here, we detail the technical considerations required to perform transventricular and transaortic mitral valve repair as well as discuss the advantages for employing these less conventional approaches. PMID- 26539352 TI - Maze permutations during minimally invasive mitral valve surgery. AB - Surgical ablation for atrial fibrillation is most frequently done in the concomitant setting, and most commonly with mitral valve surgery. Minimally invasive surgical techniques for the treatment of atrial fibrillation have developed contemporaneously with techniques for minimally invasive mitral valve surgery. As in traditional surgery for atrial fibrillation, there are many different permutations of ablations for the less invasive approaches. Lesion sets can vary from simple pulmonary vein isolation (PVI) to full bi-atrial lesions that completely reproduce the traditional cut-and-sew Cox Maze III procedure with variable efficacy in restoring sinus rhythm. Additionally, treatment of the atrial appendage can be done through minimally invasive approaches without any ablation at all in an attempt to mitigate the risk of stroke. Finally, hybrid procedures combining minimally invasive surgery and catheter-based ablation are being developed that might augment surgical treatment of atrial fibrillation at the time of minimally invasive mitral valve repair. These various permutations and their results are reviewed. PMID- 26539354 TI - Mitral valve repair with decalcification of the annulus and pericardial patch repair via the trans-septal approach. PMID- 26539355 TI - Classic resectional technique for mitral valve repair: triangular resection via right anterior thoracotomy. PMID- 26539356 TI - Minimally invasive mitral valve repair through a right minithoracotomy approach. PMID- 26539357 TI - Complex surgical repair of rheumatic mitral stenosis. PMID- 26539358 TI - Concomitant Cox-Maze IV techniques during mitral valve surgery. PMID- 26539359 TI - Special considerations in mitral valve repair during aortic root surgery. PMID- 26539360 TI - Rheumatic heart disease. PMID- 26539361 TI - Alternative placebo treatment arms in trials: Implications may vary with differential results. PMID- 26539362 TI - Sodium glucose co-transporter inhibitors - A new class of old drugs. AB - Sodium glucose co-transporter (SGLT) inhibitors are a new class of drugs which are used in the pharmacotherapy of Type-II diabetes, which happens to be a major risk factor for developing both micro as well as macro-vascular complications. These drugs inhibit the glucose reabsorption by inhibiting SGLT, which exhibits a novel and promising mechanism of action by promoting the urinary glucose excretion hence providing a basis of therapeutic intervention. Results of SGLT-II inhibitors are very encouraging as there is a significant elevation of GLP-1 level, which forms the basis of relevance in treatment of diabetes. It targets the HbA1C and keeps a check on its levels. It also exerts other positive benefits such as weight loss, reduction in blood glucose levels, reduction in blood pressure and improvement in insulin resistance and beta-cell dysfunction: All contributing to effective glycemic control. SGLT inhibition will develop as effective modality as it has the capability of inhibiting reabsorption of greater percentage of filtered glucose load. PMID- 26539363 TI - Cracked tooth syndrome: Overview of literature. AB - Pain is defined as an "unpleasant sensory and emotional feeling which is associated with actual or potential injury of tissue or expressed in terms of such injury." Tooth pain usually refers to pain around the teeth or jaws mainly as a result of a dental condition. Mostly, toothaches are caused by a carious cavity, a broken tooth, an exposed tooth root or gum disease. The toothache may sometimes be the result of radiating pain from structures in the vicinity of tooth and jaws (cardiac pain, ear, nose, throat pain, and sinusitis). Therefore, evaluation by both dentists and physicians are sometimes necessary to diagnose medical illnesses causing "toothache." Cracked tooth syndrome is a major diagnostic challenge in clinical practice. Accurate diagnosis and appropriate treatment are complicated due to lack of awareness of this condition and its bizarre clinical features. Early diagnosis has been linked with successful restorative management and good prognosis. This article provides a detailed literature on the causes, classification, signs and symptoms, diagnosis, and treatment planning of cracked tooth syndrome. PMID- 26539364 TI - Hematoxylin and eosin stain shows a high sensitivity but sub-optimal specificity in demonstrating iron pigment in liver biopsies. AB - BACKGROUND: Perls' stain is routinely used to demonstrate iron in liver biopsies. We tested the hypothesis that it may be unnecessary in cases, where no iron or another similar pigment was seen on the routine hematoxylin and eosin (H and E) stained section. AIM: The aim of this study was to evaluate the efficiency of H and E stain in demonstrating iron in liver biopsies as well as to determine the possibility of replacing Perls' stain with H and E stain. MATERIALS AND METHODS: Two hundred pairs of slides of liver biopsies were taken from the archival files of the Department of Pathology from 2006 to 2011. Perls' and H and E slides were independently reviewed for the presence of iron. RESULTS: Hundred and one cases showed the presence of iron using H and E stain. 84 of 86 cases showed positive iron using both Perls' and H and E stains. Seventeen cases were positive using H and E stain but negative with Perls'. Only two cases did not show the presence of iron using H and E stain. Ninety-seven cases were negative using both Perls' and H and E stains. H and E stain showed a sensitivity, specificity, accuracy, positive predictive valve, and negative predictive value of 97.67%, 85.08%, 90.5%, 83.16%, and 97.98%, respectively. CONCLUSION: We demonstrate that the H and E stain is a sensitive method to detect iron pigment in liver biopsies, particularly when present in large quantities. A negative H and E stain might obviate the need for extra Perls' staining, thus saving costs and shortening report turn-around times. PMID- 26539365 TI - Association study of methylenetetrahydrofolate reductase A1298C mutation with cerebral venous thrombosis risk in an Iranian population. AB - BACKGROUND: Cerebral venous thrombosis (CVT) is an uncommon condition characterized by severe clinical manifestations and high mortality rate. There is limited data on the role of methylenetetrahydrofolate reductase (MTHFR) A1298C mutation as a risk factor for CVT development in Iranians. AIM: The aim was to investigate a possible association between fasting plasma homocysteine (Hcy) levels, MTHFR A1298C mutation, and CVT in Iranian population. MATERIALS AND METHODS: The study population consisted of 50 patients with a diagnosis of CVT (20-63 years old) and 75 healthy subjects (18-65 years old) as control. Genotyping of the MTHFR A1298C mutation and Hcy measurement was carried out by polymerase chain reaction-restriction fragment length polymorphism technique and enzyme immunoassay method, respectively. RESULTS: Fasting plasma total Hcy levels were significantly higher in CVT patients than controls (P = 0.015). No significant differences were observed in the MTHFR A1298C genotypes frequency between CVT patients and controls (P > 0.05). The frequency of the 1298C allele was 36% and 37.5% in CVT patients and controls, respectively and did not differ significantly between the two groups (P = 0.16). CONCLUSIONS: Our study demonstrated that MTHFR A1298Cmutation is not a significant risk factor for CVT. PMID- 26539366 TI - Estimation of a single motor unit's threshold and activation range, a study on patients with muscular disorders. AB - BACKGROUND: In clinical neurophysiology, threshold tracking studies are used to evaluate the functionality of a muscle through studying the functionality of its motor units (MUs) that govern the muscle. The functionality of an MU can be quantified by estimation of its excitability properties via MU's stimulus response curve. In this study, we aim to develop a model-based approach to estimate MU's threshold mean and its activation range as indications of MU's excitability. This is a different approach from routine strategies in neurophysiology, which are mostly subjective. METHODS: To assess the excitability of a single MU, needle electromyography examination was used to obtain the axonal activity of that MU. To improve estimation, the examination was repeated several times on individuals. Replication of experiment introduces serial correlation between observations. We account for this correlation by using a mixed-effects model. We investigate the appropriateness of classical logistic mixed-effects model and its Bayesian formulation for estimation purpose. RESULTS: Both classical and Bayesian models can obtain a reliable estimation of MU's threshold. However, we found Bayesian approach to provide a better estimate of MU's activation range. Moreover, if data contain outliers both classical and Bayesian methods are vulnerable to some extent. CONCLUSIONS: Compared to the classical approach, Bayesian method is more flexible in dealing with overdispersion and provides more robust estimation of MU's parameters. PMID- 26539367 TI - Presence of pathogenicity island related and plasmid encoded virulence genes in cytolethal distending toxin producing Escherichia coli isolates from diarrheal cases. AB - CONTEXT: Mobile genetic elements such as plasmids, bacteriophages, insertion elements, and genomic islands play a critical role in virulence of bacterial pathogens. These elements transfer horizontally and could play an important role in the evolution and virulence of many pathogens. A broad spectrum of gram negative bacterial species has been shown to produce a cytolethal distending toxin (CDT). On the other hand, Shiga toxin producing Escherichia coli are the one carry virulence genes such as stx 1 and stx 2 (Shiga toxin) and these genes can be acquired by horizontal gene transfer. AIM: The aim of this study was to investigate the presence of other virulence associated genes among CDT producing E. coli strains. MATERIALS AND METHODS: Thirty CDT positive strains isolated from patients with diarrhea were characterized. Thereafter, the association with virulent genetic elements in known pathogenicity islands (PAIs) was assessed by polymerase chain reaction. RESULTS: In this study, it was shown that the most CDT producing E. coli isolates express Shiga toxin. Moreover, the presence of prophages framing cdt genes (like P2 phage) was also identified in each cdt-type genomic group. Flanked regions of cdt-I, cdt-IV, and cdt-V-type was similar to plasmid sequences while cdt-II and cdt-III-type regions similarity with hypothetical protein (orf3) was observed. CONCLUSION: The occurrence of each cdt type groups with specific virulence genes and PAI genetic elements is indicative of horizontal gene transfer by these mobile genetic elements, which could lead to diversity among the isolates. PMID- 26539368 TI - Tolerance of skin grafts to postoperative radiotherapy. AB - AIM: The aim was to evaluate the integrity and functional outcomes of skin grafts following external beam radiotherapy (EBRT). MATERIALS AND METHODS: A prospective study of 15 patients, in whom EBRT was planned after their wound coverage with split-thickness skin graft (STSG). Parameters evaluated include defect size, time to postoperative radiotherapy, total radiotherapy dose, delays and interruptions in radiotherapy, wound complications, and the need for further surgical interventions. RESULTS: In all the 15 (6 men, 9 women) patients of STSG, radical doses of EBRT, that is, 50-70 Gy in 25-35 fractions are delivered over around 6 weeks. All STSGs were placed on healthy vascular tissue beds. Median time to initial radiotherapy after grafting was 3 weeks (range 3-6 weeks). There were no interruptions in radiotherapy treatment. In one patient, there was partial skin graft loss after radiotherapy that was adequately managed with conservative treatment. No patient requires further surgical intervention. CONCLUSION: Adjuvant postoperative radiotherapy can be delivered to STSGs without significant complications. Postoperative radiotherapy can be started as early as 3-4 weeks after skin grafting. Skin grafts should be placed on well-vascularized healthy tissues. Minor skin graft loss resulting from postoperative radiotherapy can usually be treated conservatively. PMID- 26539369 TI - Evaluation of N-terminal pro-B-type natriuretic peptide and high-sensitivity C reactive protein relationship with features of metabolic syndrome in high-risk subgroups for cardiovascular disease. AB - AIM: This study evaluating N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitivity C-reactive protein (hs-CRP) relationship with features of the metabolic syndrome (MS) in high risk subgroups for cardiovascular disease (CVD) in Trinidad. MATERIALS AND METHODS: The sample population consisted of 160 subjects, 78 of whom were African and 82 East Indian attending medical outpatient clinics of regional health authority hospitals of Trinidad. RESULTS: Systolic blood pressure, triglycerides, glucose and insulin as well as NT-pro-BNP were elevated among the East Indian sub-population, with only systolic blood pressure being significantly elevated among the African sub-population. NT-pro-BNP and hs CRP demonstrated significant correlations with respect to the majority of independent risk factors inclusive of Adult Treatment Panel III and American Association of Clinical Endocrinologists defined criteria for MS. NT-pro-BNP demonstrated stronger association among the East Indian sub-population as compared to that of the African sub-population. CONCLUSIONS: Our study showed that the East Indian subgroup was more at risk for CVD as evidenced by the fulfillment of the criteria for diagnosis of MS and therefore NT-pro-BNP and hs CRP can be deemed a suitable marker for MS. PMID- 26539370 TI - Apelin protect against multiple organ injury following hemorrhagic shock and decrease the inflammatory response. AB - INTRODUCTION: Hemorrhagic shock (HS) result in multiple organ injury and inflammatory response that lead to death. The exact mechanism is not clear. Apelin is an endogenous ligand of orphan G-protein coupled receptor APJ. Apelin has anti-inflammatory effects on the release of inflammatory mediators. OBJECTIVES: To examine the protective effects of apelin against multiple organ injury and the possible involvement of inflammatory pathways. METHODOLOGY: Male Sprague-Dawley rats (300-350 g) were subjected to hemorrhage over 60 min to reach a mean arterial blood pressure of 40 mmHg. Then, rats were treated or not with 1 mL of 10 nm/L apelin-13 intraarterially resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normotension. Blood samples were collected for measurement of tumor necrosis factor (TNF) using ELISA (R and D systems). Biopsies were obtained from organs for light microscopic examination. RESULTS: HS rats showed significant increase the levels of TNF. Apelin significantly lowered the production of TNF-alpha. Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in the organs of treated rats. Apelin treatment decreased the number of inflammatory cells and mitochondrial swollen in cells. CONCLUSION: Treatment with apelin before resuscitation protects against multiple organ injury in HS by attenuation the inflammatory response and might be a therapeutic target for HS. PMID- 26539371 TI - Hemovigilance: A new beginning in India. AB - Hemovigilance plays an essential role in ensuring patient safety with regard to blood transfusions. The data generated through the hemovigilance system helps in framing important changes in the whole blood transfusion process which are useful for better patient safety. This article briefly describes the history of hemovigilance, why the need of hemovigilance was felt and also illustrates about the Hemovigilance Program of India. PMID- 26539372 TI - A true cornual pregnancy with placenta percreta resulting in a viable fetus. AB - Cornual pregnancy is uncommon among ectopic pregnancies. A diagnosis of cornual pregnancy remains challenging, and rupture of a cornual pregnancy causes catastrophic consequence due to massive bleeding. In very rare circumstances, cornual pregnancies can result in a viable fetus. We report a case of a 24-year old primigravida who presented to us with complaints of decrease fetal movements at 37(+5) weeks. Ultrasound revealed a single live intrauterine fetus with anterior low lying placenta with severe oligohydramnios (amniotic fluid index = 1.8). Emergency cesarean section was done and intraoperatively it was diagnosed as a case of placenta percreta with pregnancy in right noncommunicating horn of uterus. Right cornual resection with right salpingectomy done. Uterus, left fallopian tube and bilateral ovary were healthy. Postoperative period was uneventful. PMID- 26539373 TI - A giant spider nevus in a patient of hepatitis C-related liver cirrhosis: A rare presentation. AB - Spider nevi are benign vascular lesions mostly seen in patients with decompensated liver cirrhosis. Mostly, these are seen in the superior vena cava distribution and are small with pinhead size central vessel. Giant spider nevus is rarely seen and hence this report. PMID- 26539374 TI - An unusual case of retained abdominal pregnancy for 36 years in a postmenopausal woman. AB - Abdominal pregnancy is a rare form of ectopic pregnancy which occurs due to ruptured uterine or tubal pregnancy into the abdomen. Fetal loss is a common complication of these pregnancies and patient presents with acute abdominal pain which is a surgical emergency. Another rare but established complication of this ectopic pregnancy is fetal demise with the dead fetus being retained in the abdomen. It gets macerated and mummified over a period of time and is mostly detected incidentally during imaging. Radiological imaging has hallmark appearances of such a macerated fetus showing multiple fetal parts embedded in a calcified sac termed as lithopedion or stone baby. We report a unique case of retained abdominal pregnancy for 36 years in a 60-year-old postmenopausal female presented with abdominal pain and difficulty in micturition. Computed tomography showed multiple fetal bones in the abdomen surrounded by a membrane which was surprisingly not calcified. PMID- 26539375 TI - Repair of cleft alveolar bone with bioactive glass material using Z-plasty flap. AB - Multiple literature addresses cleft alveolar bone, with little consensus on the preferred surgical technique. Hence, we described a transoral approach for repair of cleft alveolar bone with Z-plasty and using bioactive glass. STUDY DESIGN: Case presentation and surgical technique description. In conclusion, transoral mucosal repair cleft alveolar bone Z-plasty using bioactive glass demonstrated an alternative easy and simple approach for augmentation of unilateral alveolar cleft patients. PMID- 26539376 TI - Extranodal natural killer/T-cell lymphoma, nasal type: A great pretender. AB - Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is a rare Epstein Barr virus associated lymphoma seen predominantly in Asian population with a 5 years survival rate ranging from 10% to 75% depending on the stage of presentation. In this case report, we describe an unusual presentation of ENKTCL, which in its early stages was clinically misdiagnosed as buccal space infection and later on histologically as inflammatory myofibroblastic pseudotumor owing to manifold reasons. Postoperative biopsy specimen showed characteristic feature of ENKTCL both histologically and immunophenotypically. This case report underlines the importance of adequate sampling and the unusual presentation of ENKTCL nasal type with oral manifestations. PMID- 26539377 TI - Plasmacytoid variant of urothelial carcinoma: Diagnostic challenges and role of immunohistochemistry. AB - Plasmacytoid carcinoma of the urinary bladder or plasmacytoid urothelial carcinoma (PUC) is rare and only recently described a histological variant of transitional cell carcinoma. The morphological resemblance of PUC to other malignancies is a source of diagnostic dilemmas and often misdiagnosis. Immunohistochemistry plays a pivotal role in narrowing the differential diagnosis and reaching to a conclusive diagnosis. A diagnosis of PUC usually carries a dismal prognosis. Hence, correct diagnosis is important. We report here a 52-year old male with a plasmacytoid variant of urothelial carcinoma. PMID- 26539378 TI - Para-meatal urethral cyst with bladder calculi: A case report and review of the literature. AB - Para-meatal urethral cyst or median raphe cyst of the glans penis is a benign cystic lesion uncommonly encountered in prepubertal age group. Approximately, about 50 cases have been reported till date in the world literature. Herein we report a case of para-meatal urethral cyst concurrent with urinary bladder calculi. PMID- 26539379 TI - Segmental absence of intestinal musculature: A rare case report. AB - Segmental absence of intestinal musculature (SAIM) is a rare cause of intestinal obstruction and/or perforation seen in neonates, and rarely in adults. We present a case of SAIM in a 48-year-old male, who presented with acute abdominal symptoms and was repeatedly explored because of recurrence of abdominal symptoms. PMID- 26539381 TI - Laryngopyocele: Presenting with pressure symptom. AB - Laryngocele is a rare, benign dilatation of the laryngeal saccule that may extend internally into the airway or externally through the thyrohyoid membrane. When it is secondarily infected, it is called laryngopyocele, which is even rarer. Many laryngoceles are asymptomatic; sometimes, they may cause a cough, hoarseness, stridor, sore throat and may present as a swelling on one or both sides of the neck. Laryngocele may be associated with supraglottic squamous cell carcinoma. Computed tomography scan is the most effective imaging method for diagnosis. Surgery is the treatment of choice. A case of large mixed laryngopyocele in a 75 year-old male is described together with surgical management and follow-up. A review of the literature is also presented. PMID- 26539380 TI - Postoperative thrombocytosis: An unusual case report. AB - Thrombocytosis is often an incidental finding seen in 35-50% of cases and the cause determination creates a diagnostic challenge. Extreme thrombocytosis is rare and seen in 2-5.8% patients only. Among the various causes of increased platelet count, surgical procedures have attracted much attention in both experimental and clinical domain. The appearance of thrombocytosis after surgery needs to be diagnosed to establish the type of thrombocytosis (clonal or reactive), as treatment and prognosis are quite different between them. This case report is vital because of two reasons: First, the increase in platelet count is difficult to rationalize than many of the other thrombocytoses, such as those related to primary augmentation of the function of the bone marrow; second, the association of platelets with the clotting process has led to the belief that their increase after a surgical procedure is connected with the occurrence of postoperative thrombosis. This case presents an interesting finding from a patient who has undergone major abdominal surgery and has shown an unexpected perpetual increase in platelet count. PMID- 26539382 TI - Essential oils, their therapeutic properties, and implication in dentistry: A review. AB - BACKGROUND: Antibacterial treatments currently used for treatment cause several side effects, and bacterial resistance to the antibiotics is also increasing. Therefore, there is need to find better alternatives. Essential oils (EOs) have been used for treatment of various ailments since ancient times and have gained popularity over the years. Safety and efficacy of EOs have been proved by several clinical trials. This review gives an overview on the EOs, their uses, and adverse effects. MATERIALS AND METHODS: A literature search was performed in the PubMed for clinical trial studies and review articles on EOs published up to February 2015. The search was performed during March 2015. The following keywords were used: "Lavender essential oil," "cinnamon oil," "clove oil," "eucalyptus oil," "peppermint oil," "lemon EOs," and "tea tree oil." RESULTS: Total 70 relevant articles were found in PubMed database. After screening of abstracts, 52 articles were selected to be included in the present review. CONCLUSION: On the basis of the available information, it can be concluded that EOs have the potential to be developed as preventive or therapeutic agents for various oral diseases, but further clinical trials are required to establish their safety and efficacy. PMID- 26539383 TI - Recent advancements in fluoride: A systematic review. AB - To review advancements of fluoride in dentistry, a search of 21 electronic databases and World Wide Web was conducted. Relevant journals were hand searched and further information was requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. Fluoride has become an important tool in preventive dentistry. Current research is focused on the development of strategies to improve fluoride efficacy. Fluoride therapy in the form of varnish, gel, mouth rinse, or toothpaste has been used extensively as a caries-preventive intervention for over three decades. The purpose of this review is to inform the reader about new research related to the use of fluoride for the prevention of dental caries. PMID- 26539384 TI - Hamartomas of the oral cavity. AB - The majority of oral diseases present as growths and masses of varied cellular origin. Such masses may include simple hyperplasia, hamartoma, choristoma, teratoma, benign or malignant neoplasms. The distinguishing features of hamartomatous lesions are not certain, and often these non-neoplastic masses are indiscreetly denoted as neoplasms without weighing their pathology or biological behaviour. Essentially, understanding the dynamics of each of these disease processes forms an integral part of the appropriate treatment planning. PMID- 26539385 TI - The dynamic interface: A review. AB - The implant-to-tissue interface is an extremely dynamic region of interaction. Generally, a surgical procedure is performed on a patient to insert a foreign material into the bone, and the body is called on to "heal" the wound. The time schedule crucial for a healing process that is expected to result in restitution ad integrum must be determined with respect to the condition of the individual patient and tissue to be treated. There are various factors responsible for the formation of an adequate bone-implant interface. A comprehensive review of the response of bone to implant is described. PMID- 26539386 TI - Maxillary nerve block via the greater palatine canal: An old technique revisited. AB - BACKGROUND: Maxillary nerve block through the greater palatine canal is rarely adopted by dental practitioners due to lack of experience in the technique at hand which may lead into several complications. Nevertheless, it is an excellent method to achieve profound anesthesia in the maxilla. This review focuses on the anatomy as well as the indications, contraindications, and complications associated with this technique. MATERIALS AND METHODS: A literature search was performed using the scientific databases (PubMed and Google Scholar) for articles published up to December 2014 in English, using the key words "maxillary nerve block via the greater palatine canal." A total of 34 references met the inclusion criteria for this review and were selected. CONCLUSION: Block of the maxillary nerve through the greater palatine canal is a useful technique providing profound anesthesia in the hemi-maxilla, if practiced properly. PMID- 26539387 TI - Do flexible acrylic resin lingual flanges improve retention of mandibular complete dentures? AB - OBJECTIVES: The aim of this study was to compare the retention of conventional mandibular complete dentures with that of mandibular complete dentures having lingual flanges constructed with flexible acrylic resin "Versacryl." MATERIALS AND METHODS: The study sample comprised 10 completely edentulous patients. Each patient received one maxillary complete denture and two mandibular complete dentures. One mandibular denture was made of conventional heat-cured acrylic resin and the other had its lingual flanges made of flexible acrylic resin Versacryl. Digital force-meter was used to measure retention of mandibular dentures at delivery and at 2 weeks and 45 days following denture insertion. RESULTS: The statistical analysis showed that at baseline and follow-up appointments, retention of mandibular complete dentures with flexible lingual flanges was significantly greater than retention of conventional mandibular dentures (P < 0.05). In both types of mandibular dentures, retention of dentures increased significantly over the follow-up period (P < 0.05). CONCLUSIONS: The use of flexible acrylic resin lingual flanges in the construction of mandibular complete dentures improved denture retention. PMID- 26539388 TI - HIV/AIDS awareness among Iraqi medical and dental students. AB - OBJECTIVES: The present study investigated the awareness of HIV/AIDS among medical and dental students in four provinces of Iraq, a country with low HIV/AIDS frequency. MATERIALS AND METHODS: In the present study, the target population was all Iraqi medical and dental students who were in 3(rd) and 4(th) year of their education. Out of 15 medicine and 10 dentistry faculties in Iraq, 4 medical and dental faculties were randomly selected. All the students under them were invited to participate in the study (600 students) and 526 responses were received from them. We distributed the questionnaires to students during their obligatory lectures in the academic year 2012-2013. Data collection was done with a self-administered questionnaire containing knowledge and attitude questions (11 questions for each part) in addition to some demographic questions. RESULTS: A total of 526 questionnaires were received (from 319 medical students and 207 dental students). Knowledge of about half of the medical students (54%) was at an intermediate level and of 27.1% students was at a good level; more than half of the dental students (68.2%) had an intermediate level and 10.5% had a good level of knowledge. The level of attitude of medical students was 14.7% at an intermediate level and of dentistry students was 21.4% at an intermediate level. Attitude of none of the students was at good level. Knowledge and attitude scores were not significantly associated with age, gender, or marital status. However, medical students had better knowledge and attitude toward HIV/AIDS, compared to dental students. CONCLUSIONS: Some coefficients exist in knowledge and attitude of Iraqi medical and dental students toward HIV/AIDS. Results indicate that more emphasis should be placed on educating dental and medical students about HIV and other blood-borne infections. PMID- 26539389 TI - Determination of normal range for fasting salivary glucose in Type 1 diabetics. AB - BACKGROUND: The most commonly employed investigative procedure for monitoring glucose levels is blood investigation, which is invasive and gives discomfort to the patient. The purpose of the study was to validate a noninvasive, easy, and reliable method for predicting glucose levels in Type 1 diabetics and to validate a regression equation for converting the known values of salivary glucose to blood glucose. MATERIALS AND METHODS: 200 volunteers consisting of 100 Type 1 diabetics and 100 healthy controls were included, and their fasting blood and salivary glucose levels were assessed, using a semi-auto analyzer. RESULTS: On analysis of the data, statistically significant positive results were obtained (P < 0.05) when the blood and salivary glucose levels were considered among the study group participants, control group participants, and both study and control group participants. A cut-off value for salivary glucose (11.60 mg%) was defined, above which a person may be considered as diabetic. Also, the regression equation was obtained which could be used for the conversion of known value of salivary glucose to blood glucose and vice versa. CONCLUSION: The present study successfully demonstrated the role of saliva as a noninvasive and reliable marker for the prediction of glucose levels in Type 1 diabetics who show elevated blood glucose levels. PMID- 26539390 TI - DMFT index assessment, plaque pH, and microbiological analysis in children with special health care needs, India. AB - AIM: To assess the DMFT index of children with Special Health Care Needs (SHCN) in Navi Mumbai. To correlate the DMFT index with Streptococcus mutans count in the supragingival bacterial biofilm and with plaque pH. MATERIALS AND METHODS: Dental examination of 158 patients aged 5-18 years was conducted to determine the DMFT/dmft index. Supragingival plaque samples were collected from the buccal surfaces of all teeth. The samples were inoculated in mitis salivarius bacitracin agar medium and incubated at 37 degrees C for 48 h. Supragingival plaque was collected from interproximal sites of the molar area (preferably mandibular) for conducting plaque pH test. Chi-square test and Pearson's correlation were used to find the significance of the study parameters on categorical scale between the two groups. RESULTS: The mean DMFT recorded was 4.90 +/- 4.63 and the mean dmft recorded was 1.77 +/- 3.14. Mean number of S. mutans colony-forming units found was 2.961 * 10(4). Mean plaque pH recorded was 6.2. CONCLUSION: No statistically significant correlation was found between the DMFT index with the number of S. mutans and plaque pH. PMID- 26539391 TI - Use of different oral hygiene strategies in children with cerebral palsy: A comparative study. AB - BACKGROUND: Cerebral palsy (CP) is described as a group of conditions usually occurring in childhood, where children have motor dysfunction and are unable to adequately master the necessary techniques of plaque control, which ultimately leads to dental caries and periodontal problems. AIMS: The objective of this study was to educate the parents/caretakers/institution staff and children with CP about the different preventive home care measures and to evaluate the oral hygiene and gingival health status of these children before and after the institution of different preventive home care measures. MATERIALS AND METHODS: A total of 64 individuals with CP, aged between 6 and 18 years, were examined for their oral hygiene and gingival health status, after which the parents/caretakers received a health education program. The children were then randomly divided into four groups. Each group was administered a specific preventive home care measure (mechanical and chemotherapeutic) to be followed for a period of 6 weeks, and the oral hygiene and the gingival health status were recorded at the end of 1 week, 2 weeks, and 6 weeks. The data were then subjected to statistical analysis. RESULTS: In the sample of 64 children diagnosed with CP, the mean OHI(S) score among the groups of children who were given different preventive home care measures was compared at baseline, 1 week, 2 weeks, and 6 weeks. Group 4 showed a marked reduction in the OHI(S) score measured from baseline to 6 weeks, when compared to the other three groups which wa statistically very highly significant (P < 0.001) The mean MGI score was compared at baseline, 1 week, 2 weeks, and 6 weeks home, Group 4 showed a marked reduction in the MGI score measured from baseline to 6 weeks, when compared to the other three groups. When the mean MGI score was compared from baseline to 6 weeks, there was a gradual decrease in the MGI score, which was statistically highly significant between baseline and 1 week (P < 0.05) and statistically very highly significant between 1 and 2 weeks (P < 0.001). However, this improvement was not statistically significant between 2 and 6 weeks (P > 0.05). CONCLUSION: A combined mechanical and chemotherapeutic measure is highly recommended to maintain the oral hygiene and gingival health of these special children because of their difficulties and their limited abilities to control dental plaque. PMID- 26539392 TI - Evaluation of antimicrobial efficacy of Aloe vera and Meswak containing dentifrices with fluoridated dentifrice: An in vivo study. AB - AIM: To comparatively evaluate the antimicrobial efficacy of fluoridated and herbal dentifrices. MATERIALS AND METHODS: Sixty students in the age group 6-12 years with DMF/def score 0 were selected from an orphanage center. The participants were divided into four groups. In group A, no dentifrice was used; in group B, fluoride containing dentifrice was used; group C subjects used Aloe vera containing dentifrice; and in group D, Meswak containing dentifrice was used. The salivary samples were collected at the washout period of 2 days, 15 days, and 30 days and cultured on Mitis Salivarius Agar for determining Streptococcus mutans count. Results obtained were statistically analyzed using Student's t-test. RESULTS: There was an increase in bacterial count in group A where no dentifrices were used, while the bacterial count steadily decreased in groups B, C, and D by 83.7%, 80.94%, and 83.5%, respectively. CONCLUSION: Herbal dentifrices containing A. vera and Meswak can be safely recommended as an alternative to fluoridated dentifrices in terms of antimicrobial efficacy. PMID- 26539393 TI - Evaluation of the knowledge and attitude of expectant mothers about infant oral health and their oral hygiene practices. AB - BACKGROUND: Mothers play a crucial role in developing and maintaining their infants' oral hygiene. Maternal oral health, their knowledge and attitude toward infant oral health are strong indicators of their infant's oral health status. AIM: The aim of this study is to evaluate the knowledge and attitude of expectant mothers about infant oral health and their oral hygiene practices. SETTINGS AND DESIGN: This was a cross-sectional questionnaire-based survey conducted among expectant mothers in Mangalore city, India. MATERIALS AND METHODS: Three hundred expectant mothers fulfilling the inclusion and exclusion criteria were randomly selected based on convenience method over a period of 1 month. The data were collected using a self-administered questionnaire addressing the various aspects of expectant mothers' knowledge and attitude about infant oral health and their own oral hygiene practices. The analysis was done using SPSS version 16.0. RESULTS: The overall score revealed that majority of the expectant mothers had poor knowledge and attitude toward infant oral health and followed poor oral hygiene practices. Expectant mothers' educational qualification, trimester, and the number of pregnancy had a significant role in their knowledge, attitude, and oral hygiene practices. CONCLUSION: Implementation of educational programs to motivate expectant mothers and bring out awareness about the importance of oral health and their implications must be emphasized. PMID- 26539394 TI - Knowledge, attitude, and practice of needle stick and sharps injuries among dental professionals of Bangalore, India. AB - BACKGROUND: A needle stick injury (NSI) is an accidental skin-penetrating stab wound from a hollow-bore needle containing another person's blood or body fluid. Healthcare workers (HCWs) including dental professionals are at an occupational risk of exposure to blood-borne pathogens following NSIs and sharps injuries (SIs). A thorough understanding of the safe practices while handling needles and sharps is crucial for HCWs to create a risk-free work place environment. AIMS AND OBJECTIVES: To assess the knowledge, attitude, practice, and prevalence of NSIs and SIs among dental professionals in a dental college at Bangalore. MATERIALS AND METHODS: A cross-sectional survey was conducted in September 2012 using a structured, pretested, guided interview-based questionnaire that was administered to 200 dental professionals in a dental college at Bangalore to assess the knowledge, attitude, practices, and self-report information of NSIs. RESULTS: In the present study, 81.5% of dental professionals were vaccinated against hepatitis B. A total of 27.5% participants had an NSI during the previous 12 months. About 41.80% of NSIs occurred during device recapping. Most common reason for failure to report the incidents of NSIs, as declared by 29.09% of the participants, included the fear of being blamed or getting into trouble for having an NSI. CONCLUSION: The knowledge of dental professionals on NSIs and their preventive measures are inadequate; however, training on Universal Precaution Guidelines, protocols regarding post-exposure prophylaxis, and safety devices has to be provided to prevent such injuries in future among the dental professionals. PMID- 26539395 TI - Determining the association between oral malodor and periodontal disease: A case control study. AB - AIM: To assess the role of periodontal health in oral malodor causation and compare the two methods (organoleptic and Halimeter) of malodor measurement. MATERIALS AND METHODS: A total of 240 subjects (60 subjects without any evidence of periodontal disease and 180 patients with gingivitis and periodontitis) were evaluated for periodontal and oral malodor parameters. Periodontal parameters included Plaque Index (PI), Gingival Index (GI), mSBI, calculus component of OHIS, pocket depth (PD), and clinical attachment level (CAL), and oral malodor was assessed by organoleptic scores, Halimeter readings, and Tongue Coating Index (TCI). RESULTS: 80% of the sample when assessed organoleptically (i.e. 192 subjects) and 74.6% when assessed with Halimeter (i.e. 179 subjects) presented with varying degrees of halitosis. All the clinical parameters were significantly associated with oral malodor (P < 0.001). The amount of tongue coating and bleeding on probing played the most important role in increasing VSC concentration, followed by periodontal status, plaque indices, and calculus component. CONCLUSION: There was a high prevalence of halitosis in the present study population. All the clinical parameters were significantly related to oral malodor in this study, and the results indicate that determining VSC levels with Halimeter is a useful means of diagnosing halitosis objectively. PMID- 26539396 TI - Oral health knowledge, attitude, and practice in 12-year-old schoolchildren in Iran. AB - OBJECTIVE: The knowledge, attitude, practice (KAP) studies play an important role in promotion of oral health. The aim of this study was to assess oral health KAP in 12-year-old schoolchildren in Iran. MATERIALS AND METHODS: In a cross sectional study on 1554 students aged 12 years from the rural and urban areas of five provinces, KAP of subjects was assessed using a culturally adapted questionnaire. Data were analyzed using Chi-squared test, t-test, correlation coefficient, analysis of variance (ANOVA), and linear regression. Statistical significance was set at P < 0.05. RESULTS: In general, the scores of students in knowledge, attitude, and practice were 74.1 +/- 21.1%, 72.6 +/- 21.1%, and 51.8 +/- 12%, respectively. Urban students had significantly higher scores in KAP (P = 0.0001). Female students got higher scores in all the three dimensions, but the difference was significant only in brushing practice (P = 0.006). Students in Tehran (the capital city) had significantly higher scores in all fields (P = 0.0001). Parents' education and mothers' job had a significant relationship with KAP of children. CONCLUSION: The results of this study showed that 12-year-old schoolchildren in Iran had good knowledge and positive attitude. But oral health practice was not satisfactory. PMID- 26539397 TI - Social judgments made by children (10-15 year old) in relation to visible incisors trauma: School-based cross-sectional study in Khartoum state, Sudan. AB - BACKGROUND: Dento-alveolar trauma is a very common occurrence in childhood; however, there is a paucity of data about children's judgments in relation to dental status. There is a significant correlation between the children's incisor teeth status and the social judgments made by their peers. AIM: The purpose of this study was to determine whether the social attributes of a school child would be influenced by his or her incisor teeth status. Also, it is aimed to determine the judgment between male and female children and different age groups within the same class. SETTING AND DESIGN: A descriptive cross-sectional study conducted among 178 male and female children from year 5 (age 10-11 years) of primary school and year 2 of secondary school (age 14-15 years) within Khartoum state. MATERIALS AND METHODS: Students were invited to look at colored photographs of four different children's faces and to make a social judgment about these children's photographs. Using a previously validated child-centered questionnaire, participants rated subjects using a four-point Likert scale for three negative and six positive attributes. STATISTICAL ANALYSIS: Total attribute scores were tested for significant differences, according to whether the subject had visible incisor trauma or not, using t-test and analysis of variance (ANOVA) test with the level of significance set at P <= 0.05. RESULTS: Children with visible incisor trauma were given more negative attributes than children without incisor trauma (P = 0.05). Results were similar in both genders and both school years. Younger students within the same class gave more negative attributes toward children with visible incisor trauma than their older peers, with P = 0.04 and P = 0.9 for children aged 10 years and 11 years, respectively. CONCLUSION: The data confirmed results of previous studies that children with visible incisor trauma are seen more negatively than those without visible incisor trauma. PMID- 26539398 TI - In-dental office screening for diabetes mellitus using gingival crevicular blood: Retraction. AB - [This retracts the article on p. S161 in vol. 4, PMID: 25625073.]. PMID- 26539399 TI - Great learning, much networking, and friendship. PMID- 26539400 TI - Making allergic and hypersensitivity conditions visible in the International Classification of Diseases-11. AB - Understanding that the International Classification of Diseases (ICD)-11 revision would be an opportunity to standardize the code definitions for all allergic and hypersensitivity conditions, an international collaboration of Allergy Academies, including first the World Allergy Organization, the American Academy of Allergy Asthma and Immunology and the European Academy of Allergy and Clinical Immunology, has been coordinating tremendous efforts since 2013 to provide a better classification of these disorders in the new ICD-11. During this process, a strategic action plan has been constructed to keep bilateral dialog with representatives of the ICD revision by providing them scientific and technical evidences for the need of changes in the ICD framework. As a major achievement of this process, was the construction of the "allergic and hypersensitivity conditions" parented subchapter guided by the World Health Organization ICD representatives and further supported by three more regional allergy societies: the Latin American Society of Allergy, Asthma and Immunology, the American College of Allergy Asthma and Immunology, and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Believing that the outcomes of all past and future actions will impact positively to the Allergy specialty, we expect for the full approval by the United Nations in 2017. PMID- 26539401 TI - A study of treatment adherence and quality of life among adults with chronic urticaria in Singapore. AB - BACKGROUND: Chronic urticaria is a common skin condition that causes significant impact on patient's quality of life. OBJECTIVE: The purpose of the study was to assess adherence to therapy and quality of life of patients with chronic urticaria. We also aimed to study the relationship of medication adherence and quality of life of patients with chronic urticaria. METHODS: A cross sectional study was conducted with 103 patients from the dermatology clinic of National University Hospital, Singapore. Patients with chronic urticaria were asked to fill out a questionnaire for assessment of adherence to therapy and quality of life. We used the Morisky 8-Item Medication Adherence Scale to categorize adherence as high, medium, low. For assessment of quality of life, we used the validated chronic urticaria quality of life questionnaire (CU-Q2oL) by Bairadani et al. RESULTS: The highest median scores for the items measuring quality of life were interference with sleep and pruritus. We also observed that the majority of patients (71.9%) had low adherence to medical therapy. No difference in adherence was noted in patients on once daily medication or more frequent dosing. There was no significant difference in the quality of life among patients with low and medium adherence to therapy. CONCLUSION: Quality of life of patients with chronic urticaria does not depend on the patients' adherence to medications. Dosing frequency does not affect adherence in our study population. It is also important to recognize the symptoms and issues most affecting quality of life of patients with chronic urticaria, so as to improve overall management. PMID- 26539402 TI - Attitudes, practices on allergic rhinitis of generalists and specialists in Philippine National Capital Region. AB - BACKGROUND: Treatment of allergic rhinitis (AR) consistent with consensus guidelines is reported to result in better patient outcomes. However, physicians may manage patients independently of guidelines. Asian data on physician perspectives regarding AR diagnosis and management is limited. OBJECTIVE: The study objective is to assess attitudes and practices on AR of Filipino specialists and generalists. METHODS: A cross sectional survey of 100 specialists and 100 generalists was conducted from November 2014 to January 2015. A previously validated and pilot tested questionnaire was administered via structured face to face interviews. RESULTS: Specialists reported greater adequate knowledge of AR (specialists, 58%; generalists, 39%) and adherence to guidelines (specialists, 84%; generalists, 54%). Diagnostic tests were not routinely used (specialists, 81%; generalists, 92%). Monotherapy, specifically antihistamines, was preferred for mild AR. For moderate-severe AR, preference for monotherapy versus combination therapy (specialists, 49% vs. 51%; generalists, 44% vs. 56%) was similar. Both groups preferred intranasal corticosteroid spray (INCS) for monotherapy and antileukotrienes, antihistamines, INCS for combination therapy. For adjuvant therapy, specialists (82%) preferred nasal irrigation/douche. Primary consideration for choice of therapy was efficacy. Cost was the perceived reason for patients' noncompliance with treatment. CONCLUSION: Despite differences in awareness of and adherence to guidelines, prescribing patterns on management of mild and moderate-severe AR are similar among Filipino specialists and generalists. This can be attributed to a shared perception of efficacy and cost as drivers for therapeutic choices. PMID- 26539403 TI - Interleukin-10 and interleukin-5 balance in patients with active asthma, those in remission, and healthy controls. AB - BACKGROUND: The immunological mechanisms of asthma remission remain unclear although several reports have suggested that balance between T helper (Th) 2 cytokines and regulatory cytokines is related. OBJECTIVE: To study the balance between interleukin (IL) 10 and IL-5 in asthma clinical remission. METHODS: We measured the numbers of IL-5 and IL-10 producing cells in peripheral blood mononuclear cells stimulated with mite antigen obtained from patients with active asthma (group A, n = 18), patients in clinical remission (group R, n = 15) and nonatopic healthy controls (group H, n = 14). RESULTS: The numbers of IL-5 producing cells in groups A and R were significantly higher than in group H. The number of IL-5 producing cells was lower in group R than in group A, although the difference was not statistically significant. The number of IL-10 producing cells was higher in group R than in group A, although again the difference was not statistically significant. There was a significant difference in the number of IL 10 producing cells between groups A and H but not between groups R and H. The ratio of the number of IL-10 to IL-5 producing cells was highest in group H followed by groups R and A, and the differences were statistically significant for each pair of groups. CONCLUSION: Our study suggests that the IL-10/IL-5 balance is related to clinical asthma. The balance differs between patients in clinical remission and healthy controls, suggesting that allergic inflammation may continue even after clinical asthma remission. PMID- 26539404 TI - First study of pattern of anaphylaxis in a large tertiary care hospital in Saudi Arabia. AB - BACKGROUND: Anaphylaxis is a serious allergic reaction that may cause death. The signs and symptoms of anaphylaxis have not been examined in the Saudi population before. OBJECTIVE: The present study examined the signs, symptoms, triggers, and demographic patterns of patients treated for anaphylaxis at a large tertiary care hospital in Riyadh, Saudi Arabia. METHODS: All the patients who were prescribed new prescriptions of adrenaline auto-injectors (AAs) between February 1, 2010 and December 31, 2011 were included in this study. Information was collected using a standardized form. RESULTS: There were 238 patients who were analyzed. The median age at the time of first AA prescription was 15.5 years. Female to male ratio was 52:48 and 54% of the subjects were more than 18 years of age. There were some differences in the presenting signs and symptoms observed in our study compared with similar studies from around the world. Urticaria and angioedema were the most common at about 70% across all ages, followed by shortness of breath at 28%. Some triggers were found to be more common in our region. Food was the commonest trigger for anaphylaxis including tree nuts, egg, and sesame. Drug allergy was also a common trigger, with penicillins and nonsteroidal anti-inflammatory drugs being the commonest. Regarding insect allergy, samsam ant was the commonest trigger in our study. CONCLUSION: To our knowledge, this is the first study on anaphylaxis in Saudi Arabia. Some of the manifestations of anaphylaxis are significantly different in our population study compared to previously published data from other parts of the world. While managing anaphylaxis, we should be mindful of these differences. This improved understanding should help reduce the morbidity and mortality associated with anaphylaxis in our region. PMID- 26539405 TI - Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity. AB - BACKGROUND: Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. OBJECTIVE: The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. METHODS: A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0C and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. RESULTS: A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0C, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. CONCLUSION: YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity. PMID- 26539406 TI - Serum sickness reaction with skin involvement induced by bee venom injection therapy. AB - Bee venom injection therapy is an alternative treatment sometimes used for chronic inflammatory diseases, including rheumatoid arthritis and multiple sclerosis, to reduce pain. Several chemical components of bee venom have anti inflammatory effects, and apitoxin, one of the mixed components, has been used for pain prevention therapy. However, there have been no large-scale investigations regarding the efficacy or side effects or apitoxin. In this study, a case of serum sickness reaction that developed after receiving bee venom injection therapy is reported. PMID- 26539407 TI - Application of hypersensitivity skin testing in chemotherapy-induced pneumonitis. AB - Skin testing has been utilised to determine the culprit allergenic agent in drug reactions. Its application in the setting of hypersensitivity reaction relating to combination chemotherapeutic regimens may help identify the causative drug, allowing drug that is safe to be continued and avoiding limiting treatment options for patients. We report what we believe to be the first published case of hypersensitivity skin testing for gemcitabine-induced pneumonitis in a patient with metastatic leiomyosarcoma and another case of docetaxel-induced pneumonitis in a patient with metastatic HER2-positive breast cancer. PMID- 26539409 TI - Biological Effectiveness of Accelerated Protons for Chromosome Exchanges. AB - We have investigated chromosome exchanges induced in human cells by seven different energies of protons (5-2500 MeV) with LET values ranging from 0.2 to 8 keV/MUm. Human lymphocytes were irradiated in vitro and chromosome damage was assessed using three-color fluorescence in situ hybridization chromosome painting in chemically condensed chromosomes collected during the first cell division post irradiation. The relative biological effectiveness (RBE) was calculated from the initial slope of the dose-response curve for chromosome exchanges with respect to low dose and low dose-rate gamma-rays (denoted as RBEmax), and relative to acute doses of gamma-rays (denoted as RBEgammaAcute). The linear dose-response term was similar for all energies of protons, suggesting that the decrease in LET with increasing proton energy was balanced by the increase in dose from the production of nuclear secondaries. Secondary particles increase slowly above energies of a few hundred megaelectronvolts. Additional studies of 50 g/cm(2) aluminum shielded high-energy proton beams showed minor differences compared to the unshielded protons and lower RBE values found for shielded in comparison to unshielded beams of 2 or 2.5 GeV. All energies of protons produced a much higher percentage of complex-type chromosome exchanges when compared to acute doses of gamma-rays. The implications of these results for space radiation protection and proton therapy are discussed. PMID- 26539408 TI - Targeting ECM Disrupts Cancer Progression. AB - Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID- 26539410 TI - Exploring Internal Ribosome Entry Sites as Therapeutic Targets. AB - Initiation of eukaryotic mRNA translation may proceed via several different routes, each requiring a different subset of factors and relying on different and specific interactions between the mRNA and the ribosome. Two modes predominate: (i) so-called cap-dependent initiation, which requires all canonical initiation factors and is responsible for about 95-97% of all initiation events in eukaryotic cells; and (ii) cap-independent internal initiation, which requires a reduced subset of initiation factors and accounts for up to 5% of the remaining initiation events. Internal initiation relies on the presence of so-called internal ribosome entry site (IRES) elements in the 5' UTRs of some viral and cellular mRNAs. These elements (often possessing complex secondary and tertiary structures) promote efficient interaction of the mRNA with the 40S ribosome and allow for internal ribosome entry. Internal initiation of translation of specific mRNAs may contribute to development of severe disease and pathological states, such as hepatitis C and cancer. Therefore, this cellular mechanism represents an attractive target for pharmacological modulation. The purpose of this review is to provide insight into current strategies used to target viral and cellular IRESs and discuss the physiological consequences (and potential therapeutic implications) of abrogation/modulation of IRES-mediated translation. PMID- 26539411 TI - CEACAM1-4L Promotes Anchorage-Independent Growth in Melanoma. AB - Widespread metastasis is the leading course of death in many types of cancer, including malignant melanoma. The process of metastasis can be divided into a number of complex cell biological events, collectively termed the "invasion metastasis cascade." Previous reports have characterized the capability of anchorage-independent growth of cancer cells in vitro as a key characteristic of highly aggressive tumor cells, particularly with respect to metastatic potential. Biological heterogeneity as well as drastic alterations in cell adhesion of disseminated cancer cells support escape mechanisms for metastases to overcome conventional therapies. Here, we show that exclusively the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) splice variant CEACAM1-4L supports an anchorage-independent signature in malignant melanoma. These results highlight important variant-specific modulatory functions of CEACAM1 for metastatic spread in patients suffering malignant melanoma. PMID- 26539414 TI - Socio-Economic Factors, Food Habits and Phosphorus Levels in Patients on Hemodialysis. AB - BACKGROUND: Hyperphosphoremia is one of the most important risk factors for morbidity and mortality for chronic kidney disease (CKD) patients, and also, for the general population. Excessive dietary intake of phosphate (P) is one of the key factors. In particular, P in its inorganic form, which is contained in food additives, is more readily absorbed. Unfortunately, these food additives are mostly present in convenience so called "fast foods" (pre-cooked), soft drinks, which represent the typical food consumed by our hemodialysis (HD) population, composed by elderly people, mostly low-socio economic class, who often live alone. OBJECTIVES: We performed an observational retrospective multicenter study to find any association between social, cultural and economic situation, as well as food habits, and P levels in a cohort of patients on HD. Secondarily; we also examined the association between the fast food consumption and increased P levels, as well as patient compliance for P binding products. PATIENTS AND METHODS: To explore the association between socio-economic factors and serum P levels, we enrolled 100 patients on periodic HD treatment from three different units. Information on social, cultural, economic, diet habits, therapy for hyperphosphoremia and hematological and clinical parameters had been collected through specific questionnaires, administered by a physician. RESULTS: Results showed serum P level was reduced in patients who live alone compared to patients in family (P = 0.04), in self-sufficient (P = 0.05) and in patients belonging to middle-upper class, versus low-class (P = 0.003). Fast foods intake correlates with increase in P serum levels (P = 0.002), whilst the same correlation was not found for cheese intake. Our data show that socio-economic status and food habits are useful predictors of P serum levels. CONCLUSIONS: In conclusion, dietary counseling of patients on HD is mandatory. Interventions that consider the socio economic situation allow delivering important messages on foods with the least amount of P and adequate protein content, and they may be a successful strategy in targeting patients at a higher risk of hyperphosphoremia. PMID- 26539413 TI - Genetic characterization of Shiga toxin-producing Escherichia coli O26:H11 strains isolated from animal, food, and clinical samples. AB - The Shiga-toxin producing Escherichia coli (STEC) may cause serious illness in human. Here we analyze O26:H11 strains known to be among the most reported STEC strains causing human infections. Genetic characterization of strains isolated from animal, food, and clinical specimens in Argentina showed that most carried either stx 1a or stx 2a subtypes. Interestingly, stx 2a-positive O26:H11 rarely isolated from cattle in other countries showed to be an important proportion of O26:H11 strains circulating in cattle and food in our region. Seventeen percent of the isolates harbored more than one gene associated with antimicrobial resistance. In addition to stx, all strains contained the virulence genes eae beta, tir, efa, iha, espB, cif, espA, espF, espJ, nleA, nleB, nleC, and iss; and all except one contained ehxA, espP, and cba genes. On the other hand, toxB and espI genes were exclusively observed in stx 2-positive isolates, whereas katP was only found in stx 1a-positive isolates. Our results show that O26:H11 STEC strains circulating in Argentina, including those isolated from humans, cattle, and meat products, present a high pathogenic potential, and evidence that cattle can be a reservoir of O26:H11 strains harboring stx 2a. PMID- 26539415 TI - Double-J Versus External Ureteral Stents in Kidney Transplantation: A Retrospective Analysis. AB - BACKGROUND: Kidney transplantation has long been recognized as the best available therapy for end stage kidney disease. OBJECTIVES: This study aimed to compare outcomes of double-J versus percutaneous ureteral stent placement in renal transplantation. PATIENTS AND METHODS: A retrospective analysis was performed on data of renal transplantations performed at our institution in a 12-month period. In this period, external and double-J stents were used in parallel. Length of hospital stay and stent-associated complications were evaluated. RESULTS: In 76 kidney transplants, 43 external (group 1) and 33 double-J (group 2) urinary stents were used. No significant difference was observed in the number of urinary tract infections, ureteric stenosis or necrosis. The mean overall length of hospital stay was comparable in both groups (20.7 days in group 1 vs 19.3 days in group 2, P = 0.533). For patients without immunological complications, the hospital stay was significantly reduced using double-J stents (12.9 days in group 1, 10.8 days in group 2, P = 0.018). Leakage of the ureteroneocystostomy occurred in 6 out of 43 patients in group 1 (13.9%). No case of anastomotic insufficiency was observed in group 2 (P = 0.035). Macrohematuria was detected in 13 out of the 43 patients in group 1 (30.2%), compared to 3 out of 33 patients in group 2 (9.1%; P = 0.045). CONCLUSIONS: This nonrandomized comparison of stent types in kidney transplantation supports the use of prophylactic double-J stents in terms of decreased ureteric complications and reduced length of hospital stay. PMID- 26539412 TI - Salivary markers of oxidative stress in oral diseases. AB - Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID- 26539416 TI - Evaluation of Renal Histopathological Changes, as a Predictor of Recoverability of Renal Function Following Pyeloplasty for Ureteropelvic Junction Obstruction. AB - BACKGROUND: Pyeloplasty is a widely accepted treatment for ureteropelvic junction obstruction (UPJO). However, the renal function recoverability after pyeloplasty is still a matter of debate. Different parameters have been used to predict renal functional recoverability after corrective surgery, with conflicting results. OBJECTIVES: In this study, renal biopsy was carried on a series of cases of UPJO, during pyeloplasty, to study the extent of histological alterations in renal parenchyma, as a result of obstruction, and its predictive value in renal function recoverability after pyeloplasty. PATIENTS AND METHODS: We retrospectively analyzed the renal biopsy obtained during pyeloplasty in 53 adult patients. Histopathological changes were graded on a scale of 1 to 3, according to their severity, and compared with the differential renal function (DRF) revealed on the preoperative and postoperative follow up diethylene triamine pentaacetic acid (DTPA) renal scan. A Fischer's t test was used to evaluate statistical differences between values. RESULTS: This study showed a linear relationship between the severity of histological changes and renal function recovery, after pyeloplasty. Out of 24 obstructed renal units (ORU), with minimal histopathological changes (grade I), 21 ORU (87.5%), with > 35% DRF preoperatively, showed significant improvement in renal function after 12 months of pyeloplasty (P < 0.05). On the other hand, all kidneys (n = 29) with moderate to severe obstructive changes (grade II and III) had minimal improvement in DRF, after pyeloplasty, which was clinically insignificant (P > 0.05). Renal function deterioration after pyeloplasty was not observed in any of the cases. CONCLUSIONS: The severity of pathological changes in renal parenchyma, due to UPJO, is a good predictor of renal function recoverability, after pyeloplasty. The ORUs, with DRF > 35%, usually have normal (grade I) renal biopsy and might be expected to present better functional recoverability after pyeloplasty. PMID- 26539417 TI - Influence of Hemodialysis on Lipid Peroxidation, Enzymatic and Non-Enzymatic Antioxidant Capacity in Chronic Renal Failure Patients. AB - BACKGROUND: Free radical induced damages are thought to be involved in chronic kidney disease (CKD), especially in patients who are on hemodialysis (HD) for prolonged periods. Hemodialysis can influence multiple biochemical factors, several of which are useful, although the rest can be harmful and increase the severity of disease. OBJECTIVES: The purpose of this study was to evaluate the effect of the HD membrane polysulfone on oxidative stress markers, by measuring the level of lipid peroxidation and total antioxidant activity (TAC), in the blood of HD patients. PATIENTS AND METHODS: This study was carried out on 31 HD patients and 31 healthy persons, matched for age and sex, as control group. Blood samples were drawn before and after HD from arteriovenous fistulas, and once from the controls. Superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substance (TBARS) in blood hemolyzate, Glutathione peroxidase (GpX) of whole blood and TAC of plasma were measured, respectively. Then, we investigated the association between TAC of plasma, measured by ferric reducing antioxidant power (FRAP), and lipid peroxidation level with its related parameters, in HD patients. RESULTS: The SOD, GpX and CAT were decreased after HD (P < 0.05). Also, FRAP was shown to decrease after HD (P < 0.05). However, erythrocyte TBARS levels (MUmol/gr of Hb) were increased after HD, in comparison with controls, and before HD (P < 0.05). There was a significant negative correlation between TBARS and antioxidant indices, such as SOD (r = -0.67, P = 0.001), GpX (r = -0.76, P = 0.001), CAT (r = -0.63, P = 0.001) and FRAP (r = -0.84, P = 0.001). The FRAP was significantly and directly correlated with uric acid (r = +0.62, P = 0.001), SOD (r = +0.72, P = 0.001), GpX (r = +0.87, P = 0.001) and CAT (r = +0.84, P = 0.001). CONCLUSIONS: The results of our study proposed that there is a loss or inactivation of antioxidant factors, coupled with increased lipid peroxidation during the procedure of HD, possibly through the dialyzer membrane, with probable consequences on the severity of illness. PMID- 26539418 TI - Comparing the Levels of Trace Elements in Patients With Diabetic Nephropathy and Healthy Individuals. AB - BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal disease (ESRD) in developed countries. Several trace elements were reported to be changed in diabetic nephropathy. OBJECTIVES: The aim of this study was to investigate changes in serum levels of zinc, copper and chromium and their association with the incidence of ESRD in patients with diabetes. PATIENTS AND METHODS: This study was performed on 70 patients with type 2 diabetic nephropathy (macro and micro-albuminuria) and 70 healthy individuals. Samples were collected to survey metals by atomic absorption spectrophotometer. Data was analyzed by SPSS18 using descriptive and inferential analysis methods. RESULTS: Mean +/- SD levels of Zn, Cu and Cr were significantly decreased in blood samples of patients compared to healthy subjects (P < 0.01). Also the mean concentrations of Cu, Zn and Cr in drinking water of Sari were lower than the accepted limit. Only in one case, Cu was higher than the accepted limit, which was the possibility of contamination by water supply pipes. CONCLUSIONS: Cu, Zn and Cr play a specific role in the pathophysiology of diabetic nephropathy. Meanwhile in these patients, low serum levels of Cu, Zn and Cr were not associated with factors such as drinking water. Possible causes should be sought in other factors like urine, intervention factors in absorption and utilization and individual conditions. PMID- 26539419 TI - Adherence to Antihypertensives in Patients With Comorbid Condition. AB - BACKGROUND: Comorbidity has been noted as a potential barrier to proper adherence to antihypertensive medications. OBJECTIVES: We decided to investigate whether comorbidity could significantly affect adherence of Iranian patients with hypertension to their medication regimen. PATIENTS AND METHODS: Two hundred and eighty consecutive hypertensive patients were interviewed in 4 cities of Iran. The 8-item Morisky medication adherence scale (MMAS-8) (validated in Persian) was used to assess medication adherence. This scale determines adherence by scores as lower than 6 (low adherence), 6 or 7 (moderate adherence), and 8 (high adherence). Comorbidity was considered as any concomitant medical condition, which necessitates the patient to take medicine for a minimum of 6 months prior to the interviews. RESULTS: The most common comorbid conditions were ischemic heart disease (65 patients, 23.2%), diabetes mellitus (55 patients, 19.6%), and dyslipidemia (51 patients, 18.2%). Mean (+/- SD) MMAS-8 score in comorbid group was 5.68 (+/- 1.85) and in non-comorbid hypertensive patients, it was 5.83 (+/- 1.91) (P = 0.631). Mean (+/- SD) number of comorbidities was 1.53 (+/- 0.75) in low adherence group compared to 1.54 (+/- 0.77) in moderate/high adherers (P = 0.98). With increasing the number of comorbid diseases, the proportion of patients with high adherence decreased successively from 20% in those with no comorbid disease to 14.1% in those with one or two comorbid conditions, and finally 11.1% in those with 3 to 5 comorbid conditions. CONCLUSIONS: With increasing the number of comorbid conditions, the proportion of patients with high adherence decreases. In our opinion, this finding is a useful clinical note for healthcare providers when managing patients with hypertension who have other medical problems at the same time. PMID- 26539421 TI - Editorial - Hypoxia and Reoxygenation: From Basic Science to Bedside. PMID- 26539420 TI - Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Testicular Cancer: A Single Center Experiences. AB - BACKGROUND: Testicular cancer accounts for about 1 - 1.5% of all malignancies in men. Radical orchiectomy is curative in 75% of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses >= 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). OBJECTIVES: Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center. PATIENTS AND METHODS: In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center. RESULTS: Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1%), 10 (47.6%) and 3 (14.28%) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8%) had not retrograde ejaculation. CONCLUSIONS: PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center. PMID- 26539422 TI - Control of Body Weight by Eating Behavior in Children. AB - Diet, exercise, and pharmacological interventions have limited effects in counteracting the worldwide increase in pediatric body weight. Moreover, the promise that individualized drug design will work to induce weight loss appears to be exaggerated. We suggest that the reason for this limited success is that the cause of obesity has been misunderstood. Body weight is mainly under external control; our brain permits us to eat under most circumstances, and unless the financial or physical cost of food is high, eating and body weight increase by default. When energy-rich, inexpensive foods are continually available, people need external support to maintain a healthy body weight. Weight loss can thereby be achieved by continuous feedback on how much and how fast to eat on a computer screen. PMID- 26539423 TI - Long-Term Effects of Exposure to Ionizing Irradiation on Periodontal Health Status - The Tinea capitis Cohort Study. AB - Studies among long-term survivors of childhood cancer who had received high-dose irradiation therapy of 4-60 Gy, demonstrated acute and chronic dental effects, including periodontal diseases. However, the possible effects of low to moderate doses of radiation on dental health are sparse. The aim of this study is to investigate the association between childhood exposure to low-moderate doses of ionizing radiation and periodontal health following 50 years since exposure. The study population included 253 irradiated subjects (treated for Tinea capitis in the 1950s) and, 162 non-irradiated subjects. The estimated dose to the teeth was 0.2-0.4 Gy. Dental examination was performed according to the community periodontal index (CPI). Socioeconomic and health behavior variables were obtained through a personal questionnaire. Periodontal disease was operationally defined as "deep periodontal pockets." A multivariate logistic regression model was used for the association of irradiation status and other independent variables with periodontal status. The results showed that among the irradiated subjects, 23%, (95% CI 18-28%) demonstrated complete edentulousness or insufficient teeth for CPI scoring as compared to 13% (95% CI 8-19%) among the non-irradiated subjects (p = 0.01). Periodontal disease was detected among 54% of the irradiated subjects as compared to 40% of the non-irradiated (p = 0.008). Controlling for education and smoking, the ORs for the association between radiation and periodontal disease were 1.61 (95% CI 1.01-2.57) and 1.95 (95% CI 1.1-3.5) for ever never and per 1 Gy absorbed in the salivary gland, respectively. In line with other studies, a protective effect for periodontal diseases among those with high education and an increased risk for ever smokers were observed. In conclusion, childhood exposure to low-moderate doses of ionizing radiation might be associated with later outcomes of dental health. The results add valuable data on the long-term health effects of exposure to ionizing radiation and support the implementation of the ALARA principle in childhood exposure to diagnostic procedure involving radiation. PMID- 26539424 TI - International Biological Engagement Programs Facilitate Newcastle Disease Epidemiological Studies. AB - Infections of poultry species with virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), one of the most economically significant and devastating diseases for poultry producers worldwide. Biological engagement programs between the Southeast Poultry Research Laboratory (SEPRL) of the United States Department of Agriculture and laboratories from Russia, Pakistan, Ukraine, Kazakhstan, and Indonesia collectively have produced a better understanding of the genetic diversity and evolution of the viruses responsible for ND, which is crucial for the control of the disease. The data from Kazakhstan, Russia, and Ukraine identified possible migratory routes for birds that may carry both virulent NDV (vNDV) and NDV of low virulence into Europe. In addition, related NDV strains were isolated from wild birds in Ukraine and Nigeria, and from birds in continental USA, Alaska, Russia, and Japan, identifying wild birds as a possible mechanism of intercontinental spread of NDV of low virulence. More recently, the detection of new sub-genotypes of vNDV suggests that a new, fifth, panzootic of ND has already originated in Southeast Asia, extended to the Middle East, and is now entering into Eastern Europe. Despite expected challenges when multiple independent laboratories interact, many scientists from the collaborating countries have successfully been trained by SEPRL on molecular diagnostics, best laboratory practices, and critical biosecurity protocols, providing our partners the capacity to further train other employes and to identify locally the viruses that cause this OIE listed disease. These and other collaborations with partners in Mexico, Bulgaria, Israel, and Tanzania have allowed SEPRL scientists to engage in field studies, to elucidate more aspects of ND epidemiology in endemic countries, and to understand the challenges that the scientists and field veterinarians in these countries face on a daily basis. Finally, new viral characterization tools have been developed and are now available to the scientific community. PMID- 26539425 TI - Supported Employment for the Reintegration of Disability Pensioners with Mental Illnesses: A Randomized Controlled Trial. AB - Work is beneficial for the recovery from mental illness. Although the approach of individual placement and support (IPS) has been shown to be effective in Europe, it has not yet been widely implemented in European health care systems. The aim of this randomized controlled trial was to assess the effectiveness of IPS for disability pensioners with mental illnesses new on disability benefits in Switzerland. In the study at hand, 250 participants were randomly assigned to either the control or the intervention group. The participants in the intervention group received job coaching according to IPS during 2 years. The control group received no structured support. Both groups were interviewed at baseline and followed up every 6 months (baseline, 6, 12, 16, 18, 24 months) for 2 years. Primary outcome was to obtain a job in the competitive employment. IPS was more effective for the reintegration into the competitive employment market for disability pensioners than the control condition. Thirty-two percent of the participants of the intervention group and 12% of the control group obtained new jobs in the competitive employment. IPS is also effective for the reintegration into competitive employment of people with mental illness receiving disability pensions. PMID- 26539426 TI - Going Beyond the Injury: Regulatory Conditions Contributing to Latina/o Immigrants' Occupational Psychosocial Stressors. AB - BACKGROUND: Utilizing a psychosocial stress approach, we report psychosocial stressors that Latina/o immigrant day laborers in Baltimore report as workplace hazards and the contextual factors that shape these stressors. METHODS: Through a community-academic partnership, we conducted focus groups (n = 18) and key informant interviews (n = 9) using instruments developed between academics and the community partner to inquire Latina/o immigrants' jobs, hazard awareness, occupational illnesses and injuries, and reporting behaviors. We conducted a transcript-based thematic analysis. RESULTS: The psychosocial stressors that Latina/o day laborers report as dangers at work are anxiety beating the deadline and fear from wage theft, sudden termination and immigration enforcement. DISCUSSION: More attention needs to be given to Latina/o immigrant day laborers' occupational psychosocial risks. Policies should be made to lower barriers for Latina/o immigrants to report grievances to state agencies. PMID- 26539427 TI - Biosafety and Biosecurity: A Relative Risk-Based Framework for Safer, More Secure, and Sustainable Laboratory Capacity Building. AB - BACKGROUND: Laboratory capacity building is characterized by a paradox between endemicity and resources: countries with high endemicity of pathogenic agents often have low and intermittent resources (water, electricity) and capacities (laboratories, trained staff, adequate regulations). Meanwhile, countries with low endemicity of pathogenic agents often have high-containment facilities with costly infrastructure and maintenance governed by regulations. The common practice of exporting high biocontainment facilities and standards is not sustainable and concerns about biosafety and biosecurity require careful consideration. METHODS: A group at Chatham House developed a draft conceptual framework for safer, more secure, and sustainable laboratory capacity building. RESULTS: The draft generic framework is guided by the phrase "LOCAL - PEOPLE - MAKE SENSE" that represents three major principles: capacity building according to local needs (local) with an emphasis on relationship and trust building (people) and continuous outcome and impact measurement (make sense). CONCLUSION: This draft generic framework can serve as a blueprint for international policy decision-making on improving biosafety and biosecurity in laboratory capacity building, but requires more testing and detailing development. PMID- 26539428 TI - Reference materials and representative test materials to develop nanoparticle characterization methods: the NanoChOp project case. AB - This paper describes the production and characteristics of the nanoparticle test materials prepared for common use in the collaborative research project NanoChOp (Chemical and optical characterization of nanomaterials in biological systems), in casu suspensions of silica nanoparticles and CdSe/CdS/ZnS quantum dots (QDs). This paper is the first to illustrate how to assess whether nanoparticle test materials meet the requirements of a "reference material" (ISO Guide 30, 2015) or rather those of the recently defined category of "representative test material (RTM)" (ISO/TS 16195, 2013). The NanoChOp test materials were investigated with small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and centrifugal liquid sedimentation (CLS) to establish whether they complied with the required monomodal particle size distribution. The presence of impurities, aggregates, agglomerates, and viable microorganisms in the suspensions was investigated with DLS, CLS, optical and electron microscopy and via plating on nutrient agar. Suitability of surface functionalization was investigated with attenuated total reflection Fourier transform infrared spectrometry (ATR-FTIR) and via the capacity of the nanoparticles to be fluorescently labeled or to bind antibodies. Between-unit homogeneity and stability were investigated in terms of particle size and zeta potential. This paper shows that only based on the outcome of a detailed characterization process one can raise the status of a test material to RTM or reference material, and how this status depends on its intended use. PMID- 26539429 TI - Evaluation of the side effects of poly(epsilon-caprolactone) nanocapsules containing atrazine toward maize plants. AB - Poly(epsilon-caprolactone) (PCL) nanocapsules have been used as a carrier system for the herbicide atrazine, which is commonly applied to maize. We demonstrated previously that these atrazine containing polymeric nanocapsules were 10-fold more effective in the control of mustard plants (a target species), as compared to a commercial atrazine formulation. Since atrazine can have adverse effects on non-target crops, here we analyzed the effect of encapsulated atrazine on growth, physiological and oxidative stress parameters of soil-grown maize plants (Zea mays L.). One day after the post-emergence treatment with PCL nanocapsules containing atrazine (1 mg mL(-1)), maize plants presented 15 and 21% decreases in maximum quantum yield of photosystem II (PSII) and in net CO2 assimilation rate, respectively, as compared to water-sprayed plants. The same treatment led to a 1.8-fold increase in leaf lipid peroxidation in comparison with control plants. However, all of these parameters were unaffected 4 and 8 days after the application of encapsulated atrazine. These results suggested that the negative effects of atrazine were transient, probably due to the ability of maize plants to detoxify the herbicide. When encapsulated atrazine was applied at a 10-fold lower concentration (0.1 mg mL(-1)), a dosage that is still effective for weed control, no effects were detected even shortly after application. Regardless of the herbicide concentration, neither pre- nor post-emergence treatment with the PCL nanocapsules carrying atrazine resulted in the development of any macroscopic symptoms in maize leaves, and there were no impacts on shoot growth. Additionally, no effects were observed when plants were sprayed with PCL nanocapsules without atrazine. Overall, these results suggested that the use of PCL nanocapsules containing atrazine did not lead to persistent side effects in maize plants, and that the technique could offer a safe tool for weed control without affecting crop growth. PMID- 26539431 TI - Electrophoretic Deposition of Chitosan/45S5 Bioactive Glass Composite Coatings Doped with Zn and Sr. AB - In this research work, the original 45S5 bioactive glass was modified by introducing zinc and/or strontium oxide (6 mol%) in place of calcium oxide. Sr was added for its ability to stimulate bone formation and Zn for its role in bone metabolism, antibacterial properties, and anti-inflammatory effect. The glasses were produced by means of melting and quenching process. SEM and XRD analyses evidenced that Zr and Sr introduction did not modify the glass structure and morphology while compositional analysis (EDS) demonstrated the effective incorporation of these elements in the glass network. Bioactivity test in simulated body fluid (SBF) up to 1 month evidenced a reduced bioactivity kinetics for Zn-doped glasses. Doped glasses were combined with chitosan to produce organic/inorganic composite coatings on stainless steel AISI 316L by electrophoretic deposition (EPD). Two EPD processes were considered for coating development, namely direct current EPD (DC-EPD) and alternating current EPD (AC EPD). The stability of the suspension was analyzed and the deposition parameters were optimized. Tape and bending tests demonstrated a good coating-substrate adhesion for coatings containing 45S5-Sr and 45S5-ZnSr glasses, whereas the adhesion to the substrate decreased by using 45S5-Zn glass. FTIR analyses demonstrated the composite nature of coatings and SEM observations indicated that glass particles were well integrated in the polymeric matrix, the coatings were fairly homogeneous and free of cracks; moreover, the AC-EPD technique provided better results than DC-EPD in terms of coating quality. SEM, XRD analyses, and Raman spectroscopy, performed after bioactivity test in SBF solution, confirmed the bioactive behavior of 45S5-Sr-containing coating while coatings containing Zn exhibited no hydroxyapatite formation. PMID- 26539430 TI - Cold and Hot Extremozymes: Industrial Relevance and Current Trends. AB - The development of enzymes for industrial applications relies heavily on the use of microorganisms. The intrinsic properties of microbial enzymes, e.g., consistency, reproducibility, and high yields along with many others, have pushed their introduction into a wide range of products and industrial processes. Extremophilic microorganisms represent an underutilized and innovative source of novel enzymes. These microorganisms have developed unique mechanisms and molecular means to cope with extreme temperatures, acidic and basic pH, high salinity, high radiation, low water activity, and high metal concentrations among other environmental conditions. Extremophile-derived enzymes, or extremozymes, are able to catalyze chemical reactions under harsh conditions, like those found in industrial processes, which were previously not thought to be conducive for enzymatic activity. Due to their optimal activity and stability under extreme conditions, extremozymes offer new catalytic alternatives for current industrial applications. These extremozymes also represent the cornerstone for the development of environmentally friendly, efficient, and sustainable industrial technologies. Many advances in industrial biocatalysis have been achieved in recent years; however, the potential of biocatalysis through the use of extremozymes is far from being fully realized. In this article, the adaptations and significance of psychrophilic, thermophilic, and hyperthermophilic enzymes, and their applications in selected industrial markets will be reviewed. Also, the current challenges in the development and mass production of extremozymes as well as future prospects and trends for their biotechnological application will be discussed. PMID- 26539432 TI - Construction of a Modular Arsenic-Resistance Operon in E. coli and the Production of Arsenic Nanoparticles. AB - Arsenic is a widespread contaminant of both land and water around the world. Current methods of decontamination such as phytoremediation and chemical adsorbents can be resource and time intensive, and may not be suitable for some areas such as remote communities where cost and transportation are major issues. Bacterial decontamination, with strict controls preventing environmental release, may offer a cost-effective alternative or provide a financial incentive when used in combination with other remediation techniques. In this study, we have produced Escherichia coli strains containing arsenic-resistance genes from a number of sources, overexpressing them and testing their effects on arsenic resistance. While the lab E. coli strain JM109 (the "wild-type") is resistant up to 20 mM sodium arsenate, the strain containing our plasmid pEC20 is resistant up to 80 mM. When combined with our construct pArsRBCC arsenic--containing nanoparticles were observed at the cell surface; the elements of pEC20 and pArsRBCC were therefore combined in a modular construct, pArs, in order to evaluate the roles and synergistic effects of the components of the original plasmids in arsenic resistance and nanoparticle formation. We have also investigated introducing the lac operator in order to more tightly control expression from pArs. We demonstrate that our strains are able to reduce toxic forms of arsenic into stable, insoluble metallic As(0), providing one way to remove arsenate contamination, and which may also be of benefit for other heavy metals. PMID- 26539434 TI - Industrial Fermentation of Auxenochlorella protothecoides for Production of Biodiesel and Its Application in Vehicle Diesel Engines. AB - Microalgae-derived biodiesel has been regarded as a promising alternative for fossil diesel. However, the commercial production of microalgal biodiesel was halted due to its high cost. Here, we presented a pilot study on the industrial production of algal biodiesel. We began with the heterotrophic cultivation of Auxenochlorella protothecoides in a 60-m(3) fermentor that produced biomass at 3.81 g L(-1) day(-1) with a neutral lipid content at 51%. Next, we developed plate-frame filter, natural drying, and ball milling methods to harvest, dry, and extract oil from the cells at low cost. Additionally, algal biodiesel was produced for a vehicle engine test, which indicated that the microalgal biodiesel was comparable to fossil diesel but resulted in fewer emissions of particulate matter, carbon monoxide, and hydrocarbon. Altogether, our data suggested that the heterotrophic fermentation of A. protothecoides could have the potential for the future industrial production of biodiesel. PMID- 26539433 TI - The Long Path of Human Placenta, and Its Derivatives, in Regenerative Medicine. AB - In the 1800s, a baby born with a caul, a remnant of the amniotic sack or fetal membranes, was thought to be lucky, special, or protected. Over time, fetal membranes lost their legendary power and were soon considered nothing more than biological waste after birth. However, placenta tissues have reclaimed their potential and since the early 1900s an increasing body of evidence has shown that these tissues have clinical benefits in a wide range of wound repair and surgical applications. Nowadays, there is a concerted effort to understand the mechanisms underlying the beneficial effects of placental tissues, and, more recently, cells derived thereof. This review will summarize the historical and current clinical applications of human placental tissues, and cells isolated from these tissues, and discuss some mechanisms thought to be responsible for the therapeutic effects observed after tissue and/or cell transplantation. PMID- 26539435 TI - Exosomes as renal inductive signals in health and disease, and their application as diagnostic markers and therapeutic agents. AB - Cells secrete around 30-1000 nm membrane-enclosed vesicles, of which members of the subgroup between 30 and 100 nm are termed exosomes (EXs). EXs are released into the extracellular space and are widely present in body fluids and incorporated mRNA, miRNA, proteins, and signaling molecules. Increasing amounts of evidence suggest that EXs play an important role not only in cell-to-cell communication but also in various physiological and disease processes. EXs secreted by kidney cells control nephron function and are involved in kidney diseases and cancers. This makes them potential targets for diagnostic and therapeutic applications such as non-invasive biomarkers and cell-free vaccines and for use as drug delivery vehicles. This review provides an overview on the known roles of EXs in kidney development and diseases, including renal cancer. Additionally, it covers recent findings on their significance as diagnostic markers and on therapeutic applications to renal diseases and cancers. The intention is to promote an awareness of how many questions still remain open but are certainly worth investigating. PMID- 26539436 TI - Alpha Particles Induce Autophagy in Multiple Myeloma Cells. AB - OBJECTIVES: Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of alpha-RIT, i.e., RIT using alpha-particles especially for the treatment of multiple myeloma (MM). gamma-irradiation and beta-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi alpha-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation. METHODS: Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such alpha-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation. RESULTS: We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation. CONCLUSION: This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death. PMID- 26539437 TI - Interaction of Isoflavones and Endophyte-Infected Tall Fescue Seed Extract on Vasoactivity of Bovine Mesenteric Vasculature. AB - It was hypothesized that isoflavones may attenuate ergot alkaloid-induced vasoconstriction and possibly alleviate diminished contractility of vasculature after exposure to ergot alkaloids. The objective of this study was to determine if prior incubation of bovine mesenteric vasculature with the isoflavones formononetin (F), biochanin A (B), or an ergovaline-containing tall fescue seed extract (EXT) and their combinations affect ergotamine (ERT)-induced contractility. Multiple segments of mesenteric artery and vein supporting the ileal flange of the small intestine were collected from Angus heifers at slaughter (n = 5, bodyweight = 639 +/- 39 kg). Duplicates of each vessel type were incubated in tissue culture flasks at 37 degrees C with a 50-mL volume of Krebs-Henseleit buffer containing: only buffer (control); or 1 * 10(-6) M EXT; F; or B; and combinations of 1 * 10(-6) M EXT + F; 1 * 10(-6) M EXT + B; 1 * 10(-6) M F + B; or 1 * 10(-6) M EXT + F + B. After incubation for 2 h, sections were mounted in a multimyograph chamber. The ERT dose responses were normalized to 0.12 M KCl. Pretreatment with F, B, and F + B without EXT resulted in similar contractile responses to ERT in mesenteric artery and all incubations containing EXT resulted in a complete loss of vasoactivity to ERT. In mesenteric artery pretreated with EXT, treatments that contained B had higher contractile responses (P < 0.05) at ERT concentrations of 1 * 10(-7) and 5 * 10(-7) M. Also, treatments containing B tended (P < 0.1) to have greater responses than treatments without B at ERT concentrations of 1 * 10(-6), 5 * 10(-6), and 5 * 10(-5) M. In mesenteric vein pretreated with EXT, treatments containing F had greater contractile responses to ERT at 1 * 10(-5), 5 * 10(-5), and 1 * 10(-4) M (P < 0.05). These data indicated that F and B at 1 * 10(-6) M and their combination did not impact the overall contractile response to ERT in mesenteric vasculature. However, F and B may offset some of the vasoconstriction caused by prior exposure to ergot alkaloids. PMID- 26539438 TI - Rectopexy for Rectal Prolapse. AB - INTRODUCTION: Ventral mesh rectopexy (VMR) is a recognized treatment for posterior compartment pelvic organ prolapse (POP). The aim of this review is to provide a synopsis of the evidence for biological mesh use in VMR, the most widely recognized surgical technique for posterior compartment POP. METHODS: A systematic search of PubMed was conducted using the search terms "VMR," "ventral mesh rectopexy," or "mesh rectopexy." Six studies were identified. RESULTS: About 268/324 patients underwent ventral rectopexy using biological mesh with a further 6 patients having a combination of synthetic and biological mesh. Recurrence was reported in 20 patients; however, 6 were from studies where data on biological mesh could not be extracted. There are no RCTs in VMR surgery and no studies have directly compared types of biological mesh. Cross-linked porcine dermal collagen is the most commonly used mesh and has not been associated with mesh erosion, infection, or fistulation in this review. The level of evidence available on the use of biological mesh in VMR is of low quality (level 4). CONCLUSION: Ventral mesh rectopexy has become prevalent for posterior compartment POP. The evidence base for its implementation is not strong and the quality of evidence to inform choice of mesh is poor. PMID- 26539439 TI - The Use of Biological Meshes in Diaphragmatic Defects - An Evidence-Based Review of the Literature. AB - The widespread use of meshes for hiatal hernia repair has emerged in the era of laparoscopic surgery, although sporadic cases of mesh augmentation of traumatic diaphragmatic rupture have been reported. The indications for biologic meshes in diaphragmatic repair are ill defined. This systematic review aims to investigate the available evidence on the role of biologic meshes in diaphragmatic rupture and hiatal hernia repair. Limited data from sporadic case reports and case series have demonstrated that repair of traumatic diaphragmatic rupture with biologic mesh is safe technique in both the acute or chronic setting. High level evidence demonstrates short-term benefits of biologic mesh augmentation in hiatal hernia repair over primary repair, although adequate long-term data are not currently available. Long-term follow-up data suggest no benefit of hiatal hernia repair using porcine small intestine submucosa over suture repair. The effectiveness of different biologic mesh materials on hernia recurrence requires further investigation. PMID- 26539441 TI - Geriatric orthopedic co-management of older adults with hip fracture: an emerging standard. AB - Hip fracture, a common complication of fall injuries in older adults, often results in high rate of mortality, increased debility, functional loss, and worse quality of life. The value of geriatric teams and model of care for the hip fracture patients have been examined in a number of studies, and even though most studies have demonstrated potential impact in improving outcomes for the hip fracture patients, they are often observational or quasi-experimental designs that are prone to bias. In this editorial, we review the Lancet article by Prestmo and colleagues, a randomized controlled trial that demonstrated improved outcomes for hip fracture patients managed in a geriatric unit. PMID- 26539440 TI - Insights into the molecular mechanism of allostery in Hsp70s. AB - Hsp70s chaperone an amazing number and variety of cellular protein folding processes. Key to their versatility is the recognition of a short degenerate sequence motif, present in practically all polypeptides, and a bidirectional allosteric intramolecular regulation mechanism linking their N-terminal nucleotide binding domain (NBD) and their C-terminal polypeptide substrate binding domain (SBD). Through this interdomain communication ATP binding to the NBD and ATP hydrolysis control the affinity of the SBD for polypeptide substrates and substrate binding to the SBD triggers ATP hydrolysis. Genetic screens for defective variants of Hsp70s and systematic analysis of available structures of the isolated domains revealed some residues involved in allosteric control. Recent elucidation of the crystal structure of the Hsp70 homolog DnaK in the ATP bound open conformation as well as numerous NMR and mutagenesis studies bring us closer to an understanding of the communication between NBD and SBD. In this review we will discuss our current view of the allosteric control mechanism of Hsp70 chaperones. PMID- 26539442 TI - Editorial: Functional testing in the assessment of return to sports after anterior cruciate ligament reconstruction. AB - The paper entitled "Functional testing differences in anterior cruciate ligament (ACL) reconstruction patients released versus not released to return to sport" published in the American Journal of Sports Medicine (AJSM) assessed Functional Movement Screen (FMS) and the Lower Quarter Y Balance Test (YBT-LQ) as possible objective tools for evaluating a patient's readiness to return to sports after ACL reconstruction. The results suggest that many patients clinically cleared continue to have measurable function deficits and that both FMS and YBT-LQ may be used as additional tools for return to sports clearance. PMID- 26539443 TI - Editorial on the original article entitled "Permissive underfeeding of standard enteral feeding in critically ill adults" published in the New England Journal of Medicine on June 18, 2015. AB - On June 18, 2015, the New England Journal of Medicine published an article entitled "Permissive underfeeding of standard enteral feeding in critically ill adults", which reports the results of a study that examined the impact of prolonged nutritional energy restriction for critically ill patients. The study design was unique in the sense that patients in both groups received similar doses of protein during the intervention, while the non-protein energy intake was reduced in the intervention group. The study showed no differences in outcome between the two study groups. These results add to a growing body of high quality evidence against the dogmatic belief that full enteral or parenteral feeding should be given as early as possible during critical illness to prevent complications. Further research is now needed to address the question of the optimal timing to provide more nutritional support for the benefit of the patients, possibly guided by improved biomarkers that need to be developed and validated, and to investigate underlying mechanisms. PMID- 26539444 TI - Epigenetic regulations on skin wound healing: implications from current researches. PMID- 26539445 TI - Intra-articular platelet-rich plasma injections were not superior to viscosupplementation for early knee degeneration. PMID- 26539446 TI - Microbiome, a new dimension in cancer research. PMID- 26539448 TI - Birth season and vitamin D concentration in adulthood. AB - BACKGROUND: Recent evidences suggest that the season of birth may influence human development and vulnerability to develop certain diseases. METHODS: A retrospective analysis was hence carried out in the laboratory information system of the University Hospital of Parma (North-West Italy), to retrieve values of total serum vitamin D (25-hydroxyvitamin D) measured in a the whole cohort of unselected outpatients age 18 years and older referred for routine health check up during January to December 2014. Vitamin D was then stratified according to birth season. RESULTS: The study population consisted in 11,150 unselected Italian residents (median age 62 years; 8,592 women and 2,558 men). Serum vitamin D values were found to be significantly lower in subjects born in winter than in those born in spring and summer. More specifically, winter season birth was associated with 11% increased risk of developing vitamin D deficiency later in life compared to spring birth. Daily sunlight hours at birth independently predicted vitamin D concentration in adulthood. CONCLUSIONS: The results of this large, cross-sectional retrospective investigation attest that subjects born in winter have a total vitamin D concentration in adulthood that is significantly lower than those born in seasons with longer daylight periods. PMID- 26539447 TI - Expert consensus statement on parathyroid protection in thyroidectomy. PMID- 26539449 TI - Lower body mass index is associated with a higher risk of giant cell arteritis: a systematic review and meta-analysis. AB - OBJECTIVE: To characterize the possible association between body mass index (BMI) and risk of giant cell arteritis (GCA). METHODS: We conducted a systematic review of observational studies (case-control or cohort study) that (I) reported BMI of patients with GCA prior to the diagnosis of GCA compared with subjects without GCA and (II) provided relative risk (RR), odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) from its regression analysis. Meta-analysis of the included studies was then performed to estimate the pooled effect using generic variance method of DerSimonian and Laird. RESULTS: Three studies encompassing 141 patients with GCA and 85,736 controls met our eligibility criteria and were included in the data analyses. We demonstrated a statistically significant inverse relationship between BMI and risk of subsequent development of GCA as the risk increased by 8% when BMI was reduced by 1.0 kg/m(2) (pooled OR of 0.92/kg/m(2); 95% CI, 0.88-0.96). CONCLUSIONS: Our study demonstrated a statistically significant inverse relationship between BMI and risk of subsequent development GCA. The pathophysiologic link behind this negative correlation is not well-characterized and further investigation is required. PMID- 26539450 TI - Patient-related medical risk factors for periprosthetic joint infection of the hip and knee. AB - Despite advancements and improvements in methods for preventing infection, periprosthetic joint infection (PJI) is a significant complication following total joint arthroplasty (TJA). Prevention is the most important strategy to deal with this disabling complication, and prevention should begin with identifying patient-related risk factors. Medical risk factors, such as morbid obesity, malnutrition, hyperglycemia, uncontrolled diabetes mellitus, rheumatoid arthritis (RA), preoperative anemia, cardiovascular disorders, chronic renal failure, smoking, alcohol abuse and depression, should be evaluated and optimized prior to surgery. Treating patients to get laboratory values under a specified threshold or cessation of certain modifiable risk factors can decrease the risk of PJI. Although significant advances have been made in past decades to identify these risk factors, there remains some uncertainty regarding the risk factors predisposing TJA patients to PJI. Through a review of the current literature, this paper aims to comprehensively evaluate and provide a better understanding of known medical risk factors for PJI after TJA. PMID- 26539452 TI - "Liquid biopsy"-ctDNA detection with great potential and challenges. AB - Circulating tumor DNA (ctDNA) is now being extensively studied as it is a noninvasive "real-time" biomarker that can provide diagnostic and prognostic information before, during treatment and at progression. These include DNA mutations, epigenetic alterations and other forms of tumor-specific abnormalities such as microsatellite instability (MSI) and loss of heterozygosity (LOH). ctDNA is of great value in the process of cancer treatment. However, up to date, there is no strict standard considering the exact biomarker because the development and progression of cancer is extremely complicated. Also, results of the studies evaluating ctDNA are not consistent due to the different detection methods and processing. The major challenge is still assay sensitivity and specificity for analysis of ctDNA. This review mainly focuses on the tumor specific DNA mutations, epigenetic alterations as well as detecting methods of ctDNA. The advantages and disadvantages will also be discussed. PMID- 26539451 TI - Periprosthetic fractures around the femoral stem: overcoming challenges and avoiding pitfalls. AB - Management of periprosthetic fractures around the femoral stem after total hip arthroplasty (THA) represents a significant challenge and optimal treatment remains controversial. The most common treatment paradigm involves treating fractures around a well-fixed stem with osteosynthesis, whereas fractures around a loose stem require revision arthroplasty and those with poor bone require augmentation with bone graft. Paradoxically, the literature reports a higher rate of failure for osteosynthesis around prostheses considered to be well-fixed. Such a high rate of poor outcomes may result not only from difficult fracture fixation and compromised biologic healing, but also from unrecognized peri-implant pathology. Therefore, proper preoperative and intraoperative evaluation is key, and a subset of patients may benefit from alternative management. We review the appropriate methods for evaluation and treatment of Vancouver type B fractures with particular emphasis on avoiding missteps that can lead to failure. PMID- 26539454 TI - Linkage between genotype and immunological phenotype in Crohn's disease. AB - Understanding the mechanisms that drive uncontrolled inflammation in Crohn's disease (CD) remains one of the most pressing challenges in contemporary experimental medicine. Recently, a three-phased view on the pathogenesis of CD was proposed in which following the breakdown of intestinal epithelial barrier function, CD patients fail to clear the resulting infectious debris, provoking subsequent immune responses. This view on CD is attractive in that it is testable and allows better diagnosis of disease if proven correct, apart from opening a window on new therapeutic horizons. Here we shall argue, however, that this scheme may be an oversimplification in that it ignores the genetic diversity of CD and thus does not fully take into account the nature of the intestinal epithelium, which appears a non-passive actor in this disease. PMID- 26539453 TI - State of the art management of metastatic gastroesophageal cancer. AB - The anatomical locations of upper gastrointestinal (GI) tumors have changed remarkably in the western world and reflect the increasing impact of obesity and gastroesophageal (GE) reflux rather than infectious etiologies. Incidence rates of GE tumors are rising rapidly and survival rates for patients with metastatic disease remain poor. Traditionally, cytotoxic chemotherapy has had some survival advantages but increasingly complex combination regimens are limited by toxicities. The advent of molecularly targeted therapy has provided additional options for patients with advanced disease including trastuzumab and ramucirumab. There has also been detailed molecular characterization of upper GI tumors which hopefully will result in improved tailoring of clinical trial design accounting for the heterogeneity inherent in GE tumors. While numerous targeted therapies are currently being studied in clinical trials, there is much excitement regarding the role of immunotherapy in GE cancers. Although further investigation is warranted, it represents a promising avenue for patients with advanced GE tumors. PMID- 26539455 TI - Post-stroke care: an alternative model to reduce stroke related morbidity in sub Saharan Africa. AB - Stroke is a leading cause of death and disability in adults in sub-Saharan Africa (SSA). Despite its considerable burden, there has been limited progress to properly cater for and rehabilitate stroke survivors. Scarcity of rehabilitation services and grossly inadequate skilled personnel for post stroke care are distressing realities for stroke victims in SSA. There is growing evidence suggesting that home-based rehabilitation for stroke can have functional outcomes similar to patients who receive inpatient neuro-rehabilitation. The acute phase of treatment during hospitalization could be an opportunity to educate families and caregivers on how to care for stroke victims at home and provide home-based rehabilitation and care tailored to their disability. Interventions to vulgarize home-based post-stroke care could be more acceptable, affordable and accessible for victims and families. This could go a long way to palliate to the scarcity of rehabilitation services and reduce stroke related morbidity. We suggest that further research be carried out to ascertain the feasibility of this model in SSA settings, with greater emphasis on the cost effectiveness and sustainability arms of such an intervention. PMID- 26539456 TI - Refractory pulmonary artery aneurysm in Behcet's disease. AB - Pulmonary artery aneurysm (PAA) is a life-threatening complication of Behcet's disease (BD). Massive hemoptysis secondary to PAAs requires emergent endovascular treatments or surgeries. No endovascular occlusion for pulmonary artery trunk has been reported and no therapeutic algorithm exists for the rare disease. We present an endovascular occlusion and a salvage pneumonectomy for a refractory right main PAA in BD, and provide a proposal of a therapeutic algorithm. PMID- 26539457 TI - Embracing innovation: highlights in 2015 New Normal Forum for Chinese Young Surgeons in Oncology. PMID- 26539458 TI - Professor Jianxing He was granted AATS membership. PMID- 26539459 TI - Spaced Seed Data Structures for De Novo Assembly. AB - De novo assembly of the genome of a species is essential in the absence of a reference genome sequence. Many scalable assembly algorithms use the de Bruijn graph (DBG) paradigm to reconstruct genomes, where a table of subsequences of a certain length is derived from the reads, and their overlaps are analyzed to assemble sequences. Despite longer subsequences unlocking longer genomic features for assembly, associated increase in compute resources limits the practicability of DBG over other assembly archetypes already designed for longer reads. Here, we revisit the DBG paradigm to adapt it to the changing sequencing technology landscape and introduce three data structure designs for spaced seeds in the form of paired subsequences. These data structures address memory and run time constraints imposed by longer reads. We observe that when a fixed distance separates seed pairs, it provides increased sequence specificity with increased gap length. Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors. Building on this concept, we describe a data structure for tracking the frequencies of observed spaced seeds. These data structure designs will have applications in genome, transcriptome and metagenome assemblies, and read error correction. PMID- 26539460 TI - PPCM: Combing Multiple Classifiers to Improve Protein-Protein Interaction Prediction. AB - Determining protein-protein interaction (PPI) in biological systems is of considerable importance, and prediction of PPI has become a popular research area. Although different classifiers have been developed for PPI prediction, no single classifier seems to be able to predict PPI with high confidence. We postulated that by combining individual classifiers the accuracy of PPI prediction could be improved. We developed a method called protein-protein interaction prediction classifiers merger (PPCM), and this method combines output from two PPI prediction tools, GO2PPI and Phyloprof, using Random Forests algorithm. The performance of PPCM was tested by area under the curve (AUC) using an assembled Gold Standard database that contains both positive and negative PPI pairs. Our AUC test showed that PPCM significantly improved the PPI prediction accuracy over the corresponding individual classifiers. We found that additional classifiers incorporated into PPCM could lead to further improvement in the PPI prediction accuracy. Furthermore, cross species PPCM could achieve competitive and even better prediction accuracy compared to the single species PPCM. This study established a robust pipeline for PPI prediction by integrating multiple classifiers using Random Forests algorithm. This pipeline will be useful for predicting PPI in nonmodel species. PMID- 26539462 TI - Sampling and Homogenization Strategies Significantly Influence the Detection of Foodborne Pathogens in Meat. AB - Efficient preparation of food samples, comprising sampling and homogenization, for microbiological testing is an essential, yet largely neglected, component of foodstuff control. Salmonella enterica spiked chicken breasts were used as a surface contamination model whereas salami and meat paste acted as models of inner-matrix contamination. A systematic comparison of different homogenization approaches, namely, stomaching, sonication, and milling by FastPrep-24 or SpeedMill, revealed that for surface contamination a broad range of sample pretreatment steps is applicable and loss of culturability due to the homogenization procedure is marginal. In contrast, for inner-matrix contamination long treatments up to 8 min are required and only FastPrep-24 as a large-volume milling device produced consistently good recovery rates. In addition, sampling of different regions of the spiked sausages showed that pathogens are not necessarily homogenously distributed throughout the entire matrix. Instead, in meat paste the core region contained considerably more pathogens compared to the rim, whereas in the salamis the distribution was more even with an increased concentration within the intermediate region of the sausages. Our results indicate that sampling and homogenization as integral parts of food microbiology and monitoring deserve more attention to further improve food safety. PMID- 26539461 TI - Significant Microsynteny with New Evolutionary Highlights Is Detected through Comparative Genomic Sequence Analysis of Maize CCCH IX Gene Subfamily. AB - CCCH zinc finger proteins, which are characterized by the presence of three cysteine residues and one histidine residue, play important roles in RNA processing in plants. Subfamily IX CCCH proteins were recently shown to function in stress tolerances. In this study, we analyzed CCCH IX genes in Zea mays, Oryza sativa, and Sorghum bicolor. These genes, which are almost intronless, were divided into four groups based on phylogenetic analysis. Microsynteny analysis revealed microsynteny in regions of some gene pairs, indicating that segmental duplication has played an important role in the expansion of this gene family. In addition, we calculated the dates of duplication by Ks analysis, finding that all microsynteny blocks were formed after the monocot-eudicot divergence. We found that deletions, multiplications, and inversions were shown to have occurred over the course of evolution. Moreover, the Ka/Ks ratios indicated that the genes in these three grass species are under strong purifying selection. Finally, we investigated the evolutionary patterns of some gene pairs conferring tolerance to abiotic stress, laying the foundation for future functional studies of these transcription factors. PMID- 26539463 TI - Initial In Vivo Evaluation of a Novel Left Ventricular Assist Device. AB - The aim of the study was to use the ovine model to evaluate the hemocompatibility and end-organ effects of a newly developed magnetic suspension centrifugal left ventricular assist device (LVAD) by CH Biomedical Inc., Jiangsu, China. The LVADs were implanted in 6 healthy sheep, where inflow was inserted into the left ventricular apex and outflow was anastomosed to the descending aorta. All sheep received anticoagulation and antiaggregation therapy during the study. Hematologic and biochemical tests were performed to evaluate anemia, hepatorenal function, and the extent of hemolysis. The experiments lasted for up to 30 days on the beating hearts. All sheep were humanely killed at the termination of the experiments, and the end-organs were examined macroscopically and histopathologically. Autopsy was performed in all animals and there was no thrombus formation observed inside the pump. The pump's inflow and outflow conduits were also free of thrombus. Hematologic and biochemical test results were within normal limits during the study period. Postmortem examination of the explanted organs revealed no evidence of ischemia or infarction. Based on the in vivo study, this LVAD is suitable for implantation and can provide efficient support with good biocompatibility. The encouraging results in this study suggest that it is feasible to evaluate the device's long-term durability and stability. PMID- 26539464 TI - Effects of Adherence to Statin Therapy on Health Care Outcomes and Utilizations in Taiwan: A Population-Based Study. AB - AIM: Good medication adherence may decrease the probability of worse outcomes and reduce unnecessary medical care costs. This study aims to evaluate medication adherence for people on statin therapy. METHODS: National health insurance databases were analyzed from January 1, 2001, to December 31, 2007. Study samples were patients of 45 years and older adults who took statin for the first time during the study period. Medication possession ratio (MPR) was measured until the patients had hospitalization or reached the three-year follow-up period. We identified a good (MPR >= 80%) and a poor (MPR < 80%) medication adherence group to conduct statistical analyses. RESULTS: 40.8% of patients were of good medication adherence and 59.2% were of poor medication adherence. Multivariate logistic regression model indicated that the MPR >= 80% group had significantly less probability of hospitalization (P < 0.001). Being men, increasing age, higher Charlson Comorbidity Index (CCI) scores, seeking care mostly in the medical center or teaching hospitals, and living in the suburban or rural areas had higher probability of hospitalization (P < 0.05 or P < 0.001). The MPR >= 80% group spent less hospitalization expenditures (P < 0.001). CONCLUSION: Effective interventions may be applied to the poor medication adherence group in order to improve their health care outcomes. PMID- 26539465 TI - Toxoplasma gondii Infection in Pregnant Women: A Seroprevalence and Case-Control Study in Eastern China. AB - Very limited information is available concerning the epidemiology of T. gondii infection in pregnant women in eastern China. Therefore, a case-control study was conducted to estimate the seroprevalence of toxoplasmosis in this population group and to identify risk factors and possible routes of contamination. Serum samples were collected from 965 pregnant women and 965 age-matched nonpregnant control subjects in Qingdao and Weihai between October 2011 and July 2013. These were screened with enzyme linked immunoassays for the presence of anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies. 147 (15.2%) pregnant women and 167 (17.3%) control subjects were positive for anti-T. gondii IgG antibodies, while 28 (2.9%) pregnant women and 37 (3.8%) controls were positive for anti-T. gondii IgM antibodies (P = 0.256). There was no significant difference between pregnant women and nonpregnant controls with regard to the seroprevalence of either anti T. gondii IgG or IgM antibodies. Multivariate analysis showed that T. gondii infection was associated with location, cats in home, contact with cats and dogs, and exposure to soil. The results indicated that the seroprevalence of T. gondii infection in pregnant women is high compared to most other regions of China and other East Asian countries with similar climatic conditions. PMID- 26539466 TI - Serum Caveolin-1 as a Novel Biomarker in Idiopathic Pulmonary Artery Hypertension. AB - Pulmonary arterial hypertension (PAH) is a rare disease but with significant morbidity and high mortality. There is no specific way to diagnose PAH. Thus, an easy used with good sensitivity and specificity biomarker of PAH is highly desirable to aid in the screening, diagnosis, and follow-up. Caveolin-1 (Cav1) is the structural protein of caveolae and is highly expressed in type I pneumocytes. Lungs tissues from idiopathic PAH (IPAH) patients showed decreased expression of Cav1 in vascular endothelial cells. Therefore, we developed a direct sandwich immunoassay for the determination of Cav1 in IAPH patient's serum. The result disclosed serum Cav1 level was significantly lower in IPAH than control groups. Using serum Cav1, 17.17 pg/mL as a cutoff value, the sensitivity was 0.59 and the specificity was 1.0. There were two major findings in our results. First, serum Cav1 might be a novel biomarker in the diagnosis of IPAH with fare sensitivity and good specificity. Second, Cav1 might be used to make differential diagnosis between COPD-PH and IPAH group. PMID- 26539467 TI - Molecular Epidemiology of Invasive Listeriosis due to Listeria monocytogenes in a Spanish Hospital over a Nine-Year Study Period, 2006-2014. AB - We investigated the pathogenicity, invasiveness, and genetic relatedness of 17 clinical Listeria monocytogenes stains isolated over a period of nine years (2006 2014). All isolates were phenotypically characterised and growth patterns were determined. The antimicrobial susceptibility of L. monocytogenes isolates was determined in E-tests. Invasion assays were performed with epithelial HeLa cells. Finally, L. monocytogenes isolates were subtyped by PFGE and MLST. All isolates had similar phenotypic characteristics (beta-haemolysis and lecithinase activity), and three types of growth curve were observed. Bacterial recovery rates after invasion assays ranged from 0.09% to 7.26% (1.62 +/- 0.46). MLST identified 11 sequence types (STs), and 14 PFGE profiles were obtained, indicating a high degree of genetic diversity. Genetic studies unequivocally revealed the occurrence of one outbreak of listeriosis in humans that had not previously been reported. This outbreak occurred in October 2009 and affected three patients from neighbouring towns. In conclusion, the molecular epidemiological analysis clearly revealed a cluster (three human cases, all ST1) of not previously reported listeriosis cases in northwestern Spain. Our findings indicate that molecular subtyping, in combination with epidemiological case analysis, is essential and should be implemented in routine diagnosis, to improve the tracing of the sources of outbreaks. PMID- 26539469 TI - Delivery of bFGF for Tissue Engineering by Tethering to the ECM. AB - Delivery of growth factors to target cells is an important subject in tissue engineering. Towards that end, we have developed a growth factor-tethered extracellular matrix (ECM). Here, basic fibroblast growth factor (bFGF) was tethered to extracellular matrix noncovalently. The designed ECM was comprised of 12 repeats of the APGVGV peptide motif derived from elastin as a stable structural unit and included the well-known cell adhesive RGD peptide as an active functional unit. To bind bFGF to the ECM, an acidic amino acid-rich sequence was introduced at the C-terminus of the ECM protein. It consisted of 5 repeats of 4 aspartic acids and a serine, DDDDS. bFGF has a highly basic amino acid domain. Therefore, bFGF was tethered to the ECM protein by electrostatic interaction. Cells cultured on bFGF-tethered ECM were well attached to the ECM and induced proliferation without addition of soluble bFGF. PMID- 26539468 TI - Assessing Computational Steps for CLIP-Seq Data Analysis. AB - RNA-binding protein (RBP) is a key player in regulating gene expression at the posttranscriptional level. CLIP-Seq, with the ability to provide a genome-wide map of protein-RNA interactions, has been increasingly used to decipher RBP mediated posttranscriptional regulation. Generating highly reliable binding sites from CLIP-Seq requires not only stringent library preparation but also considerable computational efforts. Here we presented a first systematic evaluation of major computational steps for identifying RBP binding sites from CLIP-Seq data, including preprocessing, the choice of control samples, peak normalization, and motif discovery. We found that avoiding PCR amplification artifacts, normalizing to input RNA or mRNAseq, and defining the background model from control samples can reduce the bias introduced by RNA abundance and improve the quality of detected binding sites. Our findings can serve as a general guideline for CLIP experiments design and the comprehensive analysis of CLIP-Seq data. PMID- 26539471 TI - A Pyrene@Micelle Sensor for Fluorescent Oxygen Sensing. AB - For most fluorescent oxygen sensors developed today, their fabrication process is either time-consuming or needs specialized knowledge. In this work, a robust fluorescent oxygen sensor is facilely constructed by dissolving pyrene molecules into CTAB aqueous solution. The as-prepared pyrene@micelle sensors have submicron sized diameter, and the concentration of utilized pyrene can be reduced as low as 0.8 mM but still can exhibit dominant excimer emission. The excimer fluorescence is sensitive to dissolved oxygen in both intensity and lifetime, and the respective Stern-Volmer plot follows a nonlinear behavior justified by a two-site model. Because of the merits of large Stokes shift (~140 nm), easy fabrication, and robustness, the pyrene@micelle sensors are very attractive for practical determination of oxygen. PMID- 26539470 TI - Medication Adherence Measures: An Overview. AB - WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently. PMID- 26539472 TI - The Use of Plant Antimicrobial Compounds for Food Preservation. AB - Foodborne disease is a global issue with significant impact on human health. With the growing consumer demand for natural preservatives to replace chemical compounds, plant antimicrobial compounds must be thoroughly investigated for their potential to serve as biopreservatives. This review paper will focus on the plant-derived products as antimicrobial agents for use in food preservation and to control foodborne pathogens in foods. Structure, modes of action, stability, and resistance to these plant compounds will be discussed as well as their application in food industries and possible technologies by which they can be delivered. Benefits as well as challenges, such as the need for further research for implementation and governmental regulation, will be highlighted. PMID- 26539473 TI - FC-NIRS: A Functional Connectivity Analysis Tool for Near-Infrared Spectroscopy Data. AB - Functional near-infrared spectroscopy (fNIRS), a promising noninvasive imaging technique, has recently become an increasingly popular tool in resting-state brain functional connectivity (FC) studies. However, the corresponding software packages for FC analysis are still lacking. To facilitate fNIRS-based human functional connectome studies, we developed a MATLAB software package called "functional connectivity analysis tool for near-infrared spectroscopy data" (FC NIRS). This package includes the main functions of fNIRS data preprocessing, quality control, FC calculation, and network analysis. Because this software has a friendly graphical user interface (GUI), FC-NIRS allows researchers to perform data analysis in an easy, flexible, and quick way. Furthermore, FC-NIRS can accomplish batch processing during data processing and analysis, thereby greatly reducing the time cost of addressing a large number of datasets. Extensive experimental results using real human brain imaging confirm the viability of the toolbox. This novel toolbox is expected to substantially facilitate fNIRS-data based human functional connectome studies. PMID- 26539475 TI - Improved Sugar Production by Optimizing Planetary Mill Pretreatment and Enzyme Hydrolysis Process. AB - This paper describes an optimization of planetary mill pretreatment and saccharification processes for improving biosugar production. Pitch pine (Pinus rigida) wood sawdust waste was used as biomass feedstock and the process parameters optimized in this study were the buffering media, the milling time, the enzyme quantity, and the incubation time. Glucose yields were improved when acetate buffer was used rather than citrate buffer. Initially, with each process variable tests, the optimal values were 100 minutes of milling, an enzyme concentration of 16 FPU/g-biomass, and a 12-hour enzymatic hydrolysis. Typically, interactions between these experimental conditions and their effects on glucose production were next investigated using RSM. Glucose yields from the Pinus rigida waste exceeded 80% with several of the conditions tested, demonstrating that milling can be used to obtain high levels of glucose bioconversion from woody biomass for biorefinery purposes. PMID- 26539474 TI - Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model. AB - Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI). The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG) and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB) scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI. PMID- 26539476 TI - Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is Associated with Alterations in Expression Patterns of Nephrin and Podocin. AB - Nephrin and podocin are known to be closely related to the pharmacological effects of angiotensin-II receptor blocker (ARB). The objectives of this study were to investigate the role of nephrin and podocin using cisplatin-induced testicular damage and to evaluate the effect of ARB. At first, we evaluated the effects of cisplatin either alone or in combination with ARB candesartan on changes in expression patterns of nephrin and podocin in the rat testes. We then conducted in vitro studies to investigate the effects of angiotensin using cultured Sertoli cells, line TM4. As a result, the expression of nephrin and podocin was shown to localize around the basal membrane of seminiferous tubules. Treatment with cisplatin resulted in a marked decrease in the expression of nephrin and podocin and induced a shift of both proteins from linear to granular expression patterns, accompanying the increased apoptotic index in the testes; these changes were partially restored by the additional administration of candesartan. In vitro studies with TM4 revealed the angiotensin-II mediated expression changes of nephrin and podocin. These findings suggest that candesartan can prevent cisplatin-induced testicular damage by regulating expression patterns of the nephrin-podocin complex in the testes. PMID- 26539477 TI - BMP-2 Grafted nHA/PLGA Hybrid Nanofiber Scaffold Stimulates Osteoblastic Cells Growth. AB - Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/degenerated tissues or organs. Natural bone is a hierarchical structure, comprised of various cells having specific functions that are regulated by sophisticated mechanisms. However, the regulation of the normal functions in damaged or injured cells is disrupted. In order to address this problem, we attempted to artificially generate a scaffold for mimicking the characteristics of the extracellular matrix at the nanoscale level to trigger osteoblastic cell growth. For this purpose, we have chemically grafted bone morphogenetic protein (BMP-2) onto the surface of L-glutamic acid modified hydroxyapatite incorporated into the PLGA nanofiber matrix. After extensive characterization using various spectroscopic techniques, the BMP-g-nHA/PLGA hybrid nanofiber scaffolds were subjected to various in vitro cytocompatibility tests. The results indicated that BMP-2 on BMP-g-nHA/PLGA hybrid nanofiber scaffolds greatly stimulated osteoblastic cells growth, contrary to the nHA/PLGA and pristine PLGA nanofiber scaffold, which are used as control. These results suggest that BMP-g-nHA/PLGA hybrid nanofiber scaffold can be used as a nanodrug carrier for the controlled and targeted delivery of BMP-2, which will open new possibilities for enhancing bone tissue regeneration and will help in the treatment of various bone-related diseases in the future. PMID- 26539478 TI - Pharmacological Preconditioning by Adenosine A2a Receptor Stimulation: Features of the Protected Liver Cell Phenotype. AB - Ischemic preconditioning (IP) of the liver by a brief interruption of the blood flow protects the damage induced by a subsequent ischemia/reperfusion (I/R) preventing parenchymal and nonparenchymal liver cell damage. The discovery of IP has shown the existence of intrinsic systems of cytoprotection whose activation can stave off the progression of irreversible tissue damage. Deciphering the molecular mediators that underlie the cytoprotective effects of preconditioning can pave the way to important therapeutic possibilities. Pharmacological activation of critical mediators of IP would be expected to emulate or even to intensify its salubrious effects. In vitro and in vivo studies have demonstrated the role of the adenosine A2a receptor (A2aR) as a trigger of liver IP. This review will provide insight into the phenotypic changes that underline the resistance to death of liver cells preconditioned by pharmacological activation of A2aR and their implications to develop innovative strategies against liver IR damage. PMID- 26539480 TI - A Decade of Progress Using Virtual Reality for Poststroke Lower Extremity Rehabilitation: Systematic Review of the Intervention Methods. AB - OBJECTIVE: To develop a systematic review of the literature, to describe the different virtual reality (VR) interventions and interactive videogames applied to the lower extremity (LE) of stroke patients, and to analyse the results according to the most frequently used outcome measures. MATERIAL AND METHODS: An electronic search of randomized trials between January 2004 and January 2014 in different databases (Medline, Cinahl, Web of Science, PEDro, and Cochrane) was carried out. Several terms (virtual reality, feedback, stroke, hemiplegia, brain injury, cerebrovascular accident, lower limb, leg, and gait) were combined, and finally 11 articles were included according to the established inclusion and exclusion criteria. RESULTS: The reviewed trials showed a high heterogeneity in terms of study design and assessment tools, which makes it difficult to compare and analyze the different types of interventions. However, most of them found a significant improvement on gait speed, balance and motor function, due to VR intervention. CONCLUSIONS: Although evidence is limited, it suggests that VR intervention (more than 10 sessions) in stroke patients may have a positive impact on balance, and gait recovery. Better results were obtained when a multimodal approach, combining VR and conventional physiotherapy, was used. Flexible software seems to adapt better to patients' requirements, allowing more specific and individual treatments. PMID- 26539481 TI - Acute Effect on Arterial Stiffness after Performing Resistance Exercise by Using the Valsalva Manoeuvre during Exertion. AB - BACKGROUND: Performing resistance exercise could lead to an increase in arterial stiffness. OBJECTIVE: We investigate the acute effect on arterial stiffness by performing Valsalva manoeuvre during resistance exercise. MATERIALS AND METHODS: Eighteen healthy young men were assigned to perform bicep curls by using two breathing techniques (exhalation and Valsalva manoeuvre during muscle contraction) on two separate study days. Carotid pulsed wave velocity (cPWV) was measured as an indicator to reflect the body central arterial stiffness using a high-resolution ultrasound system, and its value was monitored repeatedly at three predefined time intervals: before resistance exercise, immediately after exercise, and 15 minutes after exercise. RESULTS: At the 0th minute after resistance exercise was performed using the Valsalva manoeuvre during exertion, a significant increase in cPWV (4.91 m/s +/- 0.52) compared with the baseline value (4.67 m/s +/- 0.32, P = 0.008) was observed, and then it nearly returned to its baseline value at the 15th minute after exercise (4.66 m/s +/- 0.44, P = 0.010). These findings persisted after adjusting for age, body mass index, and systolic blood pressure. CONCLUSION: Our result suggests short duration of resistance exercise may provoke a transient increase in central arterial stiffness in healthy young men. PMID- 26539479 TI - Understanding Idiopathic Interstitial Pneumonia: A Gene-Based Review of Stressed Lungs. AB - Pulmonary fibrosis is the main cause of severe morbidity and mortality in idiopathic interstitial pneumonias (IIP). In the past years, there has been major progress in the discovery of genetic factors that contribute to disease. Genes with highly penetrant mutations or strongly predisposing common risk alleles have been identified in familial and sporadic IIP. This review summarizes genes harbouring causative rare mutations and replicated common predisposing alleles. To date, rare mutations in nine different genes and five risk alleles fulfil this criterion. Mutated genes represent three genes involved in surfactant homeostasis and six genes involved in telomere maintenance. We summarize gene function, gene expressing cells, and pathological consequences of genetic alterations associated with disease. Consequences of the genetic alteration include dysfunctional surfactant processing, ER stress, immune dysregulation, and maintenance of telomere length. Biological evidence shows that these processes point towards a central role for alveolar epithelial type II cell dysfunction. However, tabulation also shows that function and consequence of most common risk alleles are not known. Most importantly, the predisposition of the MUC5B risk allele to disease is not understood. We propose a mechanism whereby MUC5B decreases surface tension lowering capacity of alveolar surfactant at areas with maximal mechanical stress. PMID- 26539482 TI - Curcumin Sensitizes Hepatocellular Carcinoma Cells to Radiation via Suppression of Radiation-Induced NF-kappaB Activity. AB - The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC) cells in vitro were evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-kappaB activation, and expressions of NF-kappaB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT), NF-kappaB reporter gene, mitochondrial membrane potential (MMP), electrophoretic mobility shift (EMSA), and Western blot assays in Huh7-NF-kappaB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IkappaBalphaM) vector, a specific inhibitor of NF-kappaB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-kappaB activity and expressions of NF-kappaB downstream proteins in HCC cells. IkappaBalphaM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-kappaB activation. PMID- 26539483 TI - Comparison of Primary Models to Predict Microbial Growth by the Plate Count and Absorbance Methods. AB - The selection of a primary model to describe microbial growth in predictive food microbiology often appears to be subjective. The objective of this research was to check the performance of different mathematical models in predicting growth parameters, both by absorbance and plate count methods. For this purpose, growth curves of three different microorganisms (Bacillus cereus, Listeria monocytogenes, and Escherichia coli) grown under the same conditions, but with different initial concentrations each, were analysed. When measuring the microbial growth of each microorganism by optical density, almost all models provided quite high goodness of fit (r(2) > 0.93) for all growth curves. The growth rate remained approximately constant for all growth curves of each microorganism, when considering one growth model, but differences were found among models. Three-phase linear model provided the lowest variation for growth rate values for all three microorganisms. Baranyi model gave a variation marginally higher, despite a much better overall fitting. When measuring the microbial growth by plate count, similar results were obtained. These results provide insight into predictive microbiology and will help food microbiologists and researchers to choose the proper primary growth predictive model. PMID- 26539484 TI - Characterization of Shiga Toxigenic Escherichia coli O157 and Non-O157 Isolates from Ruminant Feces in Malaysia. AB - Shiga toxigenic Escherichia coli (STEC) O157 and several other serogroups of non O157 STEC are causative agents of severe disease in humans world-wide. The present study was conducted to characterize STEC O157 and non-O157 serogroups O26, O103, O111, O121, O45, and O145 in ruminants in Malaysia. A total of 136 ruminant feces samples were collected from 6 different farms in Peninsular Malaysia. Immunomagnetic beads were used to isolate E. coli O157 and non-O157 serogroups, while PCR was used for the detection and subtyping of STEC isolates. STEC O157:H7 was isolated from 6 (4%) feces samples and all isolates obtained carried stx 2c, eaeA-gamma1, and ehxA. Non-O157 STEC was isolated from 2 (1.5%) feces samples with one isolate carrying stx 1a, stx 2a, stx 2c, and ehxA and the other carrying stx 1a alone. The presence of STEC O157 and non-O157 in a small percentage of ruminants in this study together with their virulence characteristics suggests that they may have limited impact on public health. PMID- 26539485 TI - Shear Bond Strength of MDP-Containing Self-Adhesive Resin Cement and Y-TZP Ceramics: Effect of Phosphate Monomer-Containing Primers. AB - PURPOSE: This study was conducted to evaluate the effects of different phosphate monomer-containing primers on the shear bond strength between yttria-tetragonal zirconia polycrystal (Y-TZP) ceramics and MDP-containing self-adhesive resin cement. MATERIALS AND METHODS: Y-TZP ceramic surfaces were ground flat with #600 grit SiC paper and divided into six groups (n = 10). They were treated as follows: untreated (control), Metal/Zirconia Primer, Z-PRIME Plus, air abrasion, Metal/Zirconia Primer with air abrasion, and Z-PRIME Plus with air abrasion. MDP containing self-adhesive resin cement was applied to the surface-treated Y-TZP specimens. After thermocycling, a shear bond strength test was performed. The surfaces of the Y-TZP specimens were analyzed under a scanning electron microscope. The bond strength values were statistically analyzed using one-way analysis of variance and the Student-Newman-Keuls multiple comparison test (P < 0.05). RESULTS: The Z-PRIME Plus treatment combined with air abrasion produced the highest bond strength, followed by Z-PRIME Plus application, Metal/Zirconia Primer combined with air abrasion, air abrasion alone, and, lastly, Metal/Zirconia Primer application. The control group yielded the lowest results (P < 0.05). CONCLUSION: The application of MDP-containing primer resulted in increased bond strength between Y-TZP ceramics and MDP-containing self-adhesive resin cements. PMID- 26539486 TI - Drift of Scroll Wave Filaments in an Anisotropic Model of the Left Ventricle of the Human Heart. AB - Scroll waves are three-dimensional vortices which occur in excitable media. Their formation in the heart results in the onset of cardiac arrhythmias, and the dynamics of their filaments determine the arrhythmia type. Most studies of filament dynamics were performed in domains with simple geometries and generic description of the anisotropy of cardiac tissue. Recently, we developed an analytical model of fibre structure and anatomy of the left ventricle (LV) of the human heart. Here, we perform a systematic study of the dynamics of scroll wave filaments for the cases of positive and negative tension in this anatomical model. We study the various possible shapes of LV and different degree of anisotropy of cardiac tissue. We show that, for positive filament tension, the final position of scroll wave filament is mainly determined by the thickness of the myocardial wall but, however, anisotropy attracts the filament to the LV apex. For negative filament tension, the filament buckles, and for most cases, tends to the apex of the heart with no or slight dependency on the thickness of the LV. We discuss the mechanisms of the observed phenomena and their implications for cardiac arrhythmias. PMID- 26539487 TI - Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS. AB - The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids. PMID- 26539489 TI - Antidepressant-Like Effect of the Leaves of Pseudospondias microcarpa in Mice: Evidence for the Involvement of the Serotoninergic System, NMDA Receptor Complex, and Nitric Oxide Pathway. AB - Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect of Pseudospondias microcarpa extract (30-300 mg kg(-1), p.o.) was investigated in two predictive models of depression--forced swimming test and tail suspension test in mice. Additionally, the mechanism(s) of action involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg kg(-1), p.o.) was blocked by p chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration of D-cycloserine and the extract potentiated the anti-immobility effect. In contrast, D-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were prevented by pretreatment of mice with L-arginine (750 mg kg(-1), i.p.) and sildenafil (5 mg kg(-1), i.p.). On the contrary, pretreatment of mice with L-NAME (30 mg kg(-1), i.p.) or methylene blue (10 mg kg(-1), i.p.) potentiated its effects. The extract produces an antidepressant-like effect in the FST and TST that is dependent on the serotoninergic system, NMDA receptor complex, and the nitric oxide pathway. PMID- 26539488 TI - The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone. AB - Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID- 26539490 TI - Low-Molecular-Weight Polyethyleneimine Grafted Polythiophene for Efficient siRNA Delivery. AB - Owing to its hydrophilicity, negative charge, small size, and labile degradation by endogenous nucleases, small interfering RNA (siRNA) delivery must be achieved by a carrier system. In this study, cationic copolymers composed of low-molecular weight polyethylenimine and polythiophenes were synthesized and evaluated as novel self-tracking siRNA delivery vectors. The concept underlying the design of these copolymers is that hydrophobicity and rigidity of polythiophenes should enhance the transport of siRNA across the cell membrane and endosomal membrane. A gel retardation assay showed that the nanosized complexes formed between the copolymers and siRNA were stable even at a molar ratio of 1 : 2. The high cellular uptake (>80%) and localization of the copolymer vectors inside the cells were easily analyzed by tracking the fluorescence of polythiophene using fluorescent microscopy and cytometry. An in vitro luciferase knockdown (KD) assay in A549-luc cells demonstrated that the siRNA complexes with more hydrophobic copolymers achieved a higher KD efficiency of 52.8% without notable cytotoxicity, indicating protein-specific KD activity rather than solely the cytotoxicity of the materials. Our polythiophene copolymers should serve as novel, efficient, low cell toxicity, and label-free siRNA delivery systems. PMID- 26539491 TI - Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib. AB - Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL 1 and their roles in dissemination and resensitization of MM to treatment. PMID- 26539492 TI - Identification of pLG72-Induced Oxidative Stress Using Systemic Approaches. AB - G72 is a schizophrenia-susceptible gene encoding a polypeptide with 153 amino acids. In 2002, it was originally proposed as an activator of D-amino acid oxidase (DAOA) that could enhance the activity of DAAO and subsequently reduce the neurotransmission of N-methyl-D-aspartate receptors. However, several controversial findings have been reported recently. Due to a number of inconsistent descriptions of pLG72's biofunctions, this study aims to identify the cellular effects induced by pLG72 in U87 cells using systems biology approaches. The analyses of transcriptomics and biological networks showed that pLG72 might be involved in the induction of oxidative stress. To confirm the in silico prediction, we tested and discovered that overexpression of pLG72 effectively enhanced reactive oxygen species (ROS) in U87 cells and, furthermore, this induction can be quenched by Tempol, a general ROS scavenger. Therefore, G72 transgenic mice presenting some psychiatric symptoms, along with the pLG72 level being significantly increased in the serum of patients with schizophrenia, have led us to propose that the ROS enhancement in mental diseases may be from the overexpression of pLG72 in brain cells. PMID- 26539493 TI - UV-Heat Treatments for the Control of Foodborne Microbial Pathogens in Chicken Broth. AB - This investigation established the process criteria for using UV-C light and mild heat (UV-H treatment) to inactivate 5-Log10 cycles (performance criterion) of common foodborne pathogen populations, Escherichia coli, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus, when inoculated in chicken broth. To define the target microorganism and the proper UV-H treatment conditions (including UV dose, treatment time, and temperature) that would achieve the stated performance criterion, mathematical equations based on Geeraerd's model were developed for each microorganism. For the sake of comparison, inactivation equations for heat treatments were also performed on the same chicken broth and for the same microorganisms. L. monocytogenes was the most UV-H resistant microorganism at all temperatures, requiring a UV dose between 6.10 J/mL (5.6 min) and 2.26 J/mL (2.09 min) to achieve 5-Log10 reductions. In comparison with UV treatments at room temperatures, the combination of UV and mild heat allowed both the UV dose and treatment time to be reduced by 30% and 63% at 55 degrees C and 60 degrees C, respectively. Compared to heat treatments, the UV-H process reduced the heating time for 5-Log10 reductions of all the investigated microorganisms in chicken broth from 20-fold to 2-fold when the operating temperature varied from 53 to 60 degrees C. PMID- 26539494 TI - Expression of HE4 in Endometrial Cancer and Its Clinical Significance. AB - The main aims of this study were to determine the expression of human epididymis protein 4 (HE4) in endometrial cancer and to explore the relationships between HE4 expression, clinicopathological parameters, and prognosis. Immunohistochemistry was used to detect HE4 expression in 102 cases of endometrial cancer, 30 cases of endometrial atypical hyperplasia, and 20 cases of normal endometrium. The positive expression rate of HE4 in endometrial carcinoma was 84.62%, significantly higher than 66.67% in atypical hyperplasia (P < 0.05) and 15.00% in normal endometrium (P < 0.0.01). With the exception of stage II, HE4 expression in endometrial cancer showed an increasing tendency with increased clinical stage (P < 0.05). The positive expression rate of HE4 increased with a decrease in the degree of differentiation. A statistically significant difference was observed between the highly differentiated group and the poorly differentiated group (P < 0.05). Mortality in endometrial cancer patients with high HE4 expression was significantly higher than that in patients with low HE4 expression (P < 0.05). Endometrial cancer patients with high HE4 expression have a poor prognosis. PMID- 26539495 TI - Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden. AB - METHODOLOGY: Since the start in 2005 virtually all patients with newly diagnosed renal cell carcinoma (RCC) in Sweden are reported to the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence, and survival. RESULTS: A total of 8556 patients with newly diagnosed RCC were registered in the NSKCR from 2005 to 2013 resulting in a coverage of 99% as compared to the Swedish Cancer Registry. The mean tumor size at detection decreased from 70 mm in 2005 to 64 mm in 2010. The proportion of patients who were incidentally detected increased. The proportion of patients with tumor stage T1a who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2012. Similarly, the proportion of laparoscopically performed radical nephrectomies increased from 6% in 2005 to 17% in 2010. During the five years of follow-up 20% of the patients had a recurrence. CONCLUSION: Over the last decade there has been a trend of earlier detection and less advanced tumors at detection in patients with RCC. An increasing proportion of the patients undergo laparoscopic and nephron-sparing procedures. PMID- 26539496 TI - A Comparison of Variant Calling Pipelines Using Genome in a Bottle as a Reference. AB - High-throughput sequencing, especially of exomes, is a popular diagnostic tool, but it is difficult to determine which tools are the best at analyzing this data. In this study, we use the NIST Genome in a Bottle results as a novel resource for validation of our exome analysis pipeline. We use six different aligners and five different variant callers to determine which pipeline, of the 30 total, performs the best on a human exome that was used to help generate the list of variants detected by the Genome in a Bottle Consortium. Of these 30 pipelines, we found that Novoalign in conjunction with GATK UnifiedGenotyper exhibited the highest sensitivity while maintaining a low number of false positives for SNVs. However, it is apparent that indels are still difficult for any pipeline to handle with none of the tools achieving an average sensitivity higher than 33% or a Positive Predictive Value (PPV) higher than 53%. Lastly, as expected, it was found that aligners can play as vital a role in variant detection as variant callers themselves. PMID- 26539497 TI - Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm. AB - Human aortic aneurysms have been associated with inflammation and vascular remodeling. Since the endocannabinoid system modulates inflammation and tissue remodeling, we investigated its components in human aortic aneurysms. We obtained anterior aortic wall samples from patients undergoing elective surgery for aortic aneurysm or coronary artery disease as controls. Histological and molecular analysis (RT-qPCR) was performed, and endocannabinoid concentration was determined using LC-MRM. Patient characteristics were comparable between the groups except for a higher incidence of arterial hypertension and diabetes in the control group. mRNA level of cannabinoid receptors was significantly higher in aneurysms than in controls. Concentration of the endocannabinoid 2 arachidonoylglycerol was significantly higher, while the second endocannabinoid anandamide and its metabolite arachidonic acid and palmitoylethanolamide were significantly lower in aneurysms. Histology revealed persistent infiltration of newly recruited leukocytes and significantly higher mononuclear cell density in adventitia of the aneurysms. Proinflammatory environment in aneurysms was shown by significant upregulation of M-CSF and PPARgamma but associated with downregulation of chemokines. We found comparable collagen-stained area between the groups, significantly decreased mRNA level of CTGF, osteopontin-1, and MMP-2, and increased TIMP-4 expression in aneurysms. Our data provides evidence for endocannabinoid system activation in human aortic aneurysms, associated with persistent low-level inflammation and vascular remodeling. PMID- 26539498 TI - The Comparative Utility of Viromer RED and Lipofectamine for Transient Gene Introduction into Glial Cells. AB - The introduction of genes into glial cells for mechanistic studies of cell function and as a therapeutic for gene delivery is an expanding field. Though viral vector based systems do exhibit good delivery efficiency and long-term production of the transgene, the need for transient gene expression, broad and rapid gene setup methodologies, and safety concerns regarding in vivo application still incentivize research into the use of nonviral gene delivery methods. In the current study, aviral gene delivery vectors based upon cationic lipid (Lipofectamine 3000) lipoplex or polyethylenimine (Viromer RED) polyplex technologies were examined in cell lines and primary glial cells for their transfection efficiencies, gene expression levels, and toxicity. The transfection efficiencies of polyplex and lipoplex agents were found to be comparable in a limited, yet similar, transfection setting, with or without serum across a number of cell types. However, differential effects on cell-specific transgene expression and reduced viability with cargo loaded polyplex were observed. Overall, our data suggests that polyplex technology could perform comparably to the market dominant lipoplex technology in transfecting various cells lines including glial cells but also stress a need for further refinement of polyplex reagents to minimize their effects on cell viability. PMID- 26539499 TI - Management of Food-Related Diarrhea Outbreak in the Emergency Department: Lessons Learned from the German STEC O104:H4 Epidemic. AB - Emergency department (ED) management of the German STEC O104:H4 outbreak in 2011 was not limited to patients being truly infected with STEC. In parallel to spread of alarming news in public media, patients suffering from diarrhea due to other reasons fearfully presented, equally. We retrospectively characterized these two cohorts for anamnestic, clinical, and laboratory findings at their first ED contact. From 15th of May to July 2011, 302 adult patients with diarrheal complaint presented at the EDs of two tertiary hospitals in Lubeck, northern Germany. Fecal testing for STEC was obtained in 245 (81%) patients: 105 were STEC positive and 140 were STEC-negative. Anamnestic characteristics (defecation rate, visible bloody diarrhea, and lower abdominal pain), abdominal tenderness, and some laboratory findings were significantly different between both cohorts but not reliable to exclude STEC. In >90% of STEC-positive patients diarrheal symptoms had started in May, reflecting the retrospective nationwide peak of infections, whereas the majority of STEC-negative patients became symptomatic in June 2011. During the German STEC O104:H4 outbreak a definite distinction at initial ED contact between STEC-positive versus STEC-negative patients by clinical judgment alone was not reliable. Fecal testing in the ED, however, might survey the outbreak of foodborne infections with the utmost precision. PMID- 26539500 TI - Normative Data for an Instrumental Assessment of the Upper-Limb Functionality. AB - Upper-limb movement analysis is important to monitor objectively rehabilitation interventions, contributing to improving the overall treatments outcomes. Simple, fast, easy-to-use, and applicable methods are required to allow routinely functional evaluation of patients with different pathologies and clinical conditions. This paper describes the Reaching and Hand-to-Mouth Evaluation Method, a fast procedure to assess the upper-limb motor control and functional ability, providing a set of normative data from 42 healthy subjects of different ages, evaluated for both the dominant and the nondominant limb motor performance. Sixteen of them were reevaluated after two weeks to perform test-retest reliability analysis. Data were clustered into three subgroups of different ages to test the method sensitivity to motor control differences. Experimental data show notable test-retest reliability in all tasks. Data from older and younger subjects show significant differences in the measures related to the ability for coordination thus showing the high sensitivity of the method to motor control differences. The presented method, provided with control data from healthy subjects, appears to be a suitable and reliable tool for the upper-limb functional assessment in the clinical environment. PMID- 26539501 TI - Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model. AB - Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH. PMID- 26539502 TI - Classification of Cancer Primary Sites Using Machine Learning and Somatic Mutations. AB - An accurate classification of human cancer, including its primary site, is important for better understanding of cancer and effective therapeutic strategies development. The available big data of somatic mutations provides us a great opportunity to investigate cancer classification using machine learning. Here, we explored the patterns of 1,760,846 somatic mutations identified from 230,255 cancer patients along with gene function information using support vector machine. Specifically, we performed a multiclass classification experiment over the 17 tumor sites using the gene symbol, somatic mutation, chromosome, and gene functional pathway as predictors for 6,751 subjects. The performance of the baseline using only gene features is 0.57 in accuracy. It was improved to 0.62 when adding the information of mutation and chromosome. Among the predictable primary tumor sites, the prediction of five primary sites (large intestine, liver, skin, pancreas, and lung) could achieve the performance with more than 0.70 in F-measure. The model of the large intestine ranked the first with 0.87 in F-measure. The results demonstrate that the somatic mutation information is useful for prediction of primary tumor sites with machine learning modeling. To our knowledge, this study is the first investigation of the primary sites classification using machine learning and somatic mutation data. PMID- 26539503 TI - Second Surgery in Insular Low-Grade Gliomas. AB - BACKGROUND: Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. OBJECTIVE: The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. METHODS: A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. RESULTS: At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P < 0.002), DeltaVT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001). CONCLUSIONS: In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery. PMID- 26539504 TI - Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing. AB - BACKGROUND: The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. METHODS: An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. RESULTS: Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. CONCLUSIONS: For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine. PMID- 26539505 TI - Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR 1183 and miR-1299 as Potential Diagnostic Biomarkers. AB - This study compared microRNA (miRNA) expression profiles between rheumatic heart disease (RHD) patients and healthy controls to investigate their differential expression and help elucidate their mechanisms of action. Microarray analysis was used to measure miRNA expression, and a total of 133 miRNAs were shown to be significantly upregulated in RHD patients compared with controls, including miR 1183 and miR-1299. A total of 137 miRNAs, including miR-4423-3p and miR-218-1-3p, were significantly downregulated in RHD patients. Quantitative real-time-PCR confirmed microarray findings for miR-1183 and miR-1299 in both tissue and plasma. Bioinformatic predictions were also made of differentially expressed miRNAs as biomarkers in RHD by databases and GO/pathway analysis. Furthermore, we investigated miR-1183 and miR-1299 expression in RHD patients with secondary pulmonary hypertension (PAH). Our findings identified an important role for miR 1299 as a direct regulator of RHD, while the observed difference in expression of miR-1183 between RHD-PAH patients with high or low pulmonary artery pressure suggests that miR-1183 overexpression may reflect pulmonary artery remodeling. miR-1183 and miR-1299 appear to play distinct roles in RHD pathogenesis accompanied by secondary PAH and could be used as potential biological markers for disease development. PMID- 26539506 TI - Effects of Dietary Supplementation of Oregano Essential Oil to Sows on Oxidative Stress Status, Lactation Feed Intake of Sows, and Piglet Performance. AB - Fifty-four multiparous large white sows were used to determine the effects of supplementing oregano essential oil (OEO) to the gestation and lactation diets on oxidative stress status, lactation feed intake, and their piglet performance. Two groups were fed diets with (OEO; n = 28) or without (Control; n = 26) supplemental 15 mg/kg OEO during gestation and lactation. The serum levels of reactive oxygen species (ROS) (P < 0.05), 8-hydroxy-deoxyguanosine (8-OHdG) (P < 0.05), and thiobarbituric acid reactive substances (TBARS) (P < 0.05) were higher during gestation (days 90 and 109) and lactation (days 1 and 3) than in early gestation (day 10). Compared with the control group, the OEO diet significantly reduced sows' serum concentrations of 8-OHdG (P < 0.05) and TBARS (P < 0.01) on day 1 of lactation. The OEO diet increased the sows' counts of faecal lactobacillus (P < 0.001) while reducing Escherichia coli (P < 0.001) and Enterococcus (P < 0.001). In the third week of lactation the treatment tended to increase sow's feed intake (P = 0.07), which resulted in higher average daily gain (P < 0.01) of piglets. Our results demonstrated that there is an increased systemic oxidative stress during late gestation and early lactation of sows. The OEO supplementation to sows' diet improved performance of their piglets, which may be attributed to the reduced oxidative stress. PMID- 26539507 TI - Twenty Years of Listeria in Brazil: Occurrence of Listeria Species and Listeria monocytogenes Serovars in Food Samples in Brazil between 1990 and 2012. AB - Listeria spp. isolated from different food products and collected from 12 Brazilian states were sent to the Laboratory of Bacterial Zoonoses (Oswaldo Cruz Institute, Brazil) for identification. The aims of this study were to characterize these isolates, from 1990 to 2012, by using biochemical, morphological, and serotyping tests, and to analyze the distribution of L. monocytogenes serotypes on different food products and geographical locations. Serotyping was performed using polyclonal somatic and flagellar antisera. Of 5953 isolates, 5770 were identified as Listeria spp., from which 3429 (59.4%) were L. innocua, 2248 (38.9%) were L. monocytogenes, and 93 (1.6%) were other Listeria spp. L. innocua was predominantly isolated from 1990 to 2000, while L. monocytogenes was from 2001 to 2012. Regarding the serotype distribution in the foods, serotypes 1/2a and 4b were most common in processed meat and ready-to-eat products, respectively; serotypes 1/2a, 1/2b, and 4b were the most common in nonprocessed meat. The results above confirm the presence of the main serotypes of L. monocytogenes in different parts of the food chain from three regions of the country and emphasize the importance of improving the control measures, as tolerance zero policy and microbiological surveillance in Brazil. PMID- 26539509 TI - Laterality of Stance during Optic Flow Stimulation in Male and Female Young Adults. AB - During self-motion, the spatial and temporal properties of the optic flow input directly influence the body sway. Men and women have anatomical and biomechanical differences that influence the postural control during visual stimulation. Given that recent findings suggest a peculiar role of each leg in the postural control of the two genders, we investigated whether the body sway during optic flow perturbances is lateralized and whether anteroposterior and mediolateral components of specific center of pressure (COP) parameters of the right and left legs differ, reexamining a previous experiment (Raffi et al. (2014)) performed with two, side-by-side, force plates. Experiments were performed on 24 right handed and right-footed young subjects. We analyzed five measures related to the COP of each foot and global data: anteroposterior and mediolateral range of oscillation, anteroposterior and mediolateral COP velocity, and sway area. Results showed that men consistently had larger COP parameters than women. The values of the COP parameters were correlated between the two feet only in the mediolateral axis of women. These findings suggest that optic flow stimulation causes asymmetry in postural balance and different lateralization of postural controls in men and women. PMID- 26539508 TI - Middle Cerebral Artery Atherosclerotic Plaques in Recent Small Subcortical Infarction: A Three-Dimensional High-resolution MR Study. AB - PURPOSE: Conventional two-dimensional vessel wall imaging has been used to depict the middle cerebral artery (MCA) wall in patients with recent small subcortical infarctions (RSSIs). However, its clinical use has been limited by restricted spatial coverage, low signal-to-noise ratio (SNR), and long scan time. We used a novel three-dimensional high-resolution MR imaging (3D HR-MRI) technique to investigate the presence, locations, and contrast-enhanced patterns of MCA plaques and their relationship with RSSI. METHODS: Nineteen consecutive patients with RSSI but no luminal stenosis on MR angiography were prospectively enrolled. 3D HR-MRI was performed using a T1w-SPACE sequence at 3.0 T. The presence, locations, and contrast-enhanced patterns of the MCA plaques on the ipsilateral and contralateral sides to the RSSI were analyzed. RESULTS: Eighteen patients successfully completed the study. MCA atherosclerotic plaques occurred more frequently on the ipsilateral than the contralateral side to the RSSI (72.2% versus 33.3%, P = 0.044). The occurrence of superiorly located plaques was significantly higher on the ipsilateral than the contralateral side of the MCA (66.7% versus 27.8%; P = 0.044). CONCLUSIONS: Superiorly located plaques are closely associated with RSSI. 3D high-resolution vessel wall imaging may be a potential tool for etiologic assessment of ischemic stroke. PMID- 26539510 TI - Impact of Moderate Heat, Carvacrol, and Thymol Treatments on the Viability, Injury, and Stress Response of Listeria monocytogenes. AB - The microbial safety and stability of minimally processed foods are based on the application of combined preservative factors. Since microorganisms are able to develop adaptive networks to survive under conditions of stress, food safety may be affected, and therefore understanding of stress adaptive mechanisms plays a key role in designing safe food processing conditions. In the present study, the viability and the sublethal injury of Listeria monocytogenes exposed to moderate heat (55 degrees C) and/or essential oil compounds (carvacrol and thymol, 0.3 mM) treatments were studied. Synergistic effects were obtained when combining mild heat (55 degrees C) with one or both essential oil compounds, leading to inactivation kinetics values three to four times lower than when using heat alone. All the treatments applied caused some injury in the population. The injury levels ranged from around 20% of the surviving population under the mildest conditions to more than 99.99% under the most stringent conditions. Protein extracts of cells exposed to these treatments were analysed by two dimensional gel electrophoresis. The results obtained revealed that stressed cells exhibited differential protein expression to control cells. The proteins upregulated under these stressing conditions were implicated, among other functions, in stress response, metabolism, and protein refolding. PMID- 26539511 TI - Relative Contribution of Arms and Legs in 30 s Fully Tethered Front Crawl Swimming. AB - The relative contribution of arm stroke and leg kicking to maximal fully tethered front crawl swimming performance remains to be solved. Twenty-three national level young swimmers (12 male and 11 female) randomly performed 3 bouts of 30 s fully tethered swimming (using the whole body, only the arm stroke, and only the leg kicking). A load-cell system permitted the continuous measurement of the exerted forces, and swimming velocity was calculated from the time taken to complete a 50 m front crawl swim. As expected, with no restrictions swimmers were able to exert higher forces than that using only their arm stroke or leg kicking. Estimated relative contributions of arm stroke and leg kicking were 70.3% versus 29.7% for males and 66.6% versus 33.4% for females, with 15.6% and 13.1% force deficits, respectively. To obtain higher velocities, male swimmers are highly dependent on the maximum forces they can exert with the arm stroke (r = 0.77, P < 0.01), whereas female swimmers swimming velocity is more related to whole-body mean forces (r = 0.81, P < 0.01). The obtained results point that leg kicking plays an important role over short duration high intensity bouts and that the used methodology may be useful to identify strength and/or coordination flaws. PMID- 26539512 TI - Kinetics of Highly Sensitive Troponin T after Cardiac Surgery. AB - Perioperative myocardial infarction (PMI) confers a considerable risk in cardiac surgery settings; finding the ideal biomarker seems to be an ideal goal. Our aim was to assess the diagnostic accuracy of highly sensitive troponin T (hsTnT) in cardiac surgery settings and to define a diagnostic level for PMI diagnosis. This was a single-center prospective observational study analyzing data from all patients who underwent cardiac surgeries. The primary outcome was the diagnosis of PMI through a specific level. The secondary outcome measures were the lengths of mechanical ventilation (LOV), stay in the intensive care unit (LOSICU), and hospitalization. Based on the third universal definition of PMI, patients were divided into two groups: no PMI (Group I) and PMI (Group II). Data from 413 patients were analyzed. Nine patients fulfilled the diagnostic criteria of PMI, while 41 patients were identified with a 5-fold increase in their CK-MB (>= 120 U/L). Using ROC analysis, a hsTnT level of 3,466 ng/L or above showed 90% sensitivity and 90% specificity for the diagnosis of PMI. Secondary outcome measures in patients with PMI were significantly prolonged. In conclusion, the hsTnT levels detected here paralleled those of CK-MB and a cut-off level of 3466 ng/L could be diagnostic of PMI. PMID- 26539513 TI - Inflammatory Biomarkers in Refractory Congestive Heart Failure Patients Treated with Peritoneal Dialysis. AB - Proinflammatory cytokines play a pathogenic role in congestive heart failure. In this study, the effect of peritoneal dialysis treatment on inflammatory cytokines levels in refractory congestive heart failure patients was investigated. During the treatment, the patients reached a well-tolerated edema-free state and demonstrated significant improvement in NYHA functional class. Brain natriuretic peptide decreased significantly after 3 months of treatment and remained stable at 6 months. C-reactive protein, a plasma marker of inflammation, decreased significantly following the treatment. Circulating inflammatory cytokines TNF alpha and IL-6 decreased significantly after 3 months of peritoneal dialysis treatment and remained low at 6 months. The reduction in circulating inflammatory cytokines levels may be partly responsible for the efficacy of peritoneal dialysis for refractory congestive heart failure. PMID- 26539514 TI - Issues around the Prescription of Half Tablets in Northern Switzerland: The Irrational Case of Quetiapine. AB - BACKGROUND: Prescription of fragmented tablets is useful for individualisation of dose but includes several drawbacks. Although without score lines, the antipsychotic drug quetiapine was in 2011 the most often prescribed 1/2 tablet in discharge prescriptions at the University Hospital in Basel (USB, 671 beds). We aimed at analysing the prescription patterns of split tablets in general and of quetiapine in particular in Switzerland. METHODS: All orders of community pharmacies for unit-of-use soft pouch blisters placed at Medifilm AG, the leader company in Switzerland for repackaging into pouch blisters, were analysed. RESULTS: Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters, 8.5% were fragmented, mostly in half (87.6%), and were predominantly psycholeptics (pipamperone 15.8%). Prescription of half quetiapine appears to be a Basel specificity (highest rates of fragments and half quetiapine). CONCLUSIONS: Prescription of fragmented tablet is frequent. It represents a safety issue for the patient, and a pharmaceutical care issue for the pharmacist. In ambulatory care, the patient's cognitive and physical capacities must be clarified, suitability of the splitting of the tablet must be checked, appropriate aids must be offered, like a pill-splitting device in order to improve accuracy, and safe use of the drug must be ensured. PMID- 26539515 TI - An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer. AB - The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nonsmall cell lung cancer (NSCLC). Two partial arcs VMAT, 5 field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD) of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality. PMID- 26539516 TI - Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights. AB - OBJECTIVE: Pathomechanism of coronary slow flow phenomenon remains largely unclear now. Present study observed the pathological and angiographic evolution in a pig model of coronary slow flow. METHODS: Coronary slow flow was induced by repeat coronary injection of small doses of 40 um microspheres in 18 male domestic pigs and angiographic and pathological changes were determined at 3 hours, 7 days, and 28 days after microspheres injection. RESULTS: Compared to control group treated with coronary saline injection (n = 6) and baseline level, coronary flow was significantly reduced at 3 hours and 7 days but completely recovered at 28 days after coronary microsphere injection in slow flow group. Despite normal coronary flow at 28 days after microsphere injection, enhanced myocardial cytokine expression, left ventricular dysfunction, adverse remodelling, and ischemia/microembolism related pathological changes still persisted or even progressed from 3 hours to 28 days after coronary microsphere injection. CONCLUSIONS: Our results show that this large animal slow flow model could partly reflect the chronic angiographic, hemodynamic, and pathological changes of coronary slow flow and could be used to test new therapy strategies against the slow flow phenomenon. PMID- 26539517 TI - Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract. AB - We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO induced MI in rats. PMID- 26539518 TI - Effect of Laryngeal Squamous Cell Carcinoma Tissue Implantation on the Chick Embryo Chorioallantoic Membrane: Morphometric Measurements and Vascularity. AB - BACKGROUND: The aim of this study was to develop chick embryo chorioallantoic membrane (CAM) model of laryngeal squamous cell carcinoma (LSCC) and to evaluate the morphological and morphometric characteristics and angiogenic features of it. METHODS: Fresh LSCC tissue samples obtained from 6 patients were implanted onto 15 chick embryo CAMs. Morphological, morphometric, and angiogenic changes in the CAM and chorionic epithelium were evaluated up to 4 days after the tumor implantation. Immunohistochemical analysis (34betaE12, CD31, and Ki67 staining) was performed to detect cytokeratins and tumor endothelial cells and to evaluate the proliferative capacity of the tumor before and after implantation on the CAM. RESULTS: The implanted LSCC tissue samples survived on the CAM in all the experiments and retained the essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM (103-417%, p = 0.0001) and the chorionic epithelium (70-140%, p = 0.0001) and increase in number of blood vessels (75-148%, p = 0.0001) in the CAM. CONCLUSIONS: This study clarifies that chick embryo CAM is a relevant assay for implanting LSCC tissue and provides the first morphological and morphometric characterization of the LSCC CAM model that opens new perspectives to study this disease. PMID- 26539519 TI - Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury. AB - Activated protein C (APC) has cytoprotective effects on liver ischemia reperfusion injury (IRI). However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI. METHODS: Mice fed either normal diets (ND mice) or high fat diets (HF mice), were treated with APC or saline (control) and were performed 60 min partial IRI. Moreover, primary steatotic hepatocytes were either untreated or treated with APC and then incubated with H2O2. RESULTS: APC significantly reduced serum transaminase levels and the inflammatory cells infiltration compared with control at 4 h in ND mice and at 24 h in HF mice. APC inhibited sinusoidal endothelial injury in ND mice, but not in HF mice. In contrast, APC activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HF mice, but not in ND mice. In the in vitro study, APC significantly increased AMPK phosphorylation, ATP concentration, and survival rates of hepatocytes compared with control. CONCLUSION: During IRI in normal liver, APC attenuated initial damage by inhibiting inflammatory cell infiltration and sinusoidal endothelial injury, but not in steatotic liver. However, in steatotic liver, APC might attenuate late damage via activation of AMPK. PMID- 26539520 TI - Direct Tensile Strength and Characteristics of Dentin Restored with All-Ceramic, Resin-Composite, and Cast Metal Prostheses Cemented with Resin Adhesives. AB - A dentin-cement-prosthesis complex restored with either all-porcelain, cured resin-composite, or cast base metal alloy and cemented with either of the different resin cements was trimmed into a mini-dumbbell shape for tensile testing. The fractured surfaces and characterization of the dentin-cement interface of bonded specimens were investigated using a Scanning Electron Microscope. A significantly higher tensile strength of all-porcelain (12.5 +/- 2.2 MPa) than that of cast metal (9.2 +/- 3.5 MPa) restorations was revealed with cohesive failure in the cement and failure at the prosthesis-cement interface in Super-Bond C&B group. No significant difference in tensile strength was found among the types of restorations using the other three cements with adhesive failure on the dentin side and cohesive failure in the cured resin. SEM micrographs demonstrated the consistent hybridized dentin in Super-Bond C&B specimens that could resist degradation when immersed in hydrochloric acid followed by NaOCl solutions whereas a detached and degraded interfacial layer was found for the other cements. The results suggest that when complete hybridization of resin into dentin occurs tensile strength at the dentin-cement is higher than at the cement-prosthesis interfaces. The impermeable hybridized dentin can protect the underlying dentin and pulp from acid demineralization, even if detachment of the prosthesis has occurred. PMID- 26539521 TI - Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters. AB - RATIONALE: Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions. OBJECTIVE: We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients. METHODS AND RESULTS: In chronic HF patients (n = 81, 76 +/- 9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n = 17, 75 +/- 11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r = 0.363, P < 0.001), nitrated protein, hsCRP, and BNP and inversely to albumin. CONCLUSIONS: Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression. PMID- 26539522 TI - Volumetric Modulated Arc Therapy of the Pelvic Lymph Nodes to the Aortic Bifurcation in Higher Risk Prostate Cancer: Early Toxicity Outcomes. AB - BACKGROUND: Treatment of pelvic lymph nodes (PLNs) in higher risk prostate carcinoma is controversial. The primary focus of the study was to evaluate the early toxicity profile for this cohort of patients treated with Volumetric Modulated Arc Therapy (VMAT). METHODS: Patient, tumour, and treatment characteristics of those who received VMAT from May 2010 to December 2012 were analysed. A simplified contouring process of the PLNs to the aortic bifurcation was developed based on consensus guidelines. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were documented according to the Radiation Therapy Oncology Group (RTOG) Version 2 Guidelines. Successive Prostate Specific Antigen (PSA) values after treatment were measured on average 3 months apart. RESULTS: 113 patients were treated between May 2010 to December 2012 with a median follow-up of 14 months. No patients experienced acute grade 3 or 4 GU and GI toxicity. Only 1 patient experienced a late grade 3 GU complication. No late grade 4 GU or GI events have yet occurred. CONCLUSIONS: This study reviews the first Australian experience of VMAT in the treatment of pelvic lymph nodes in prostate cancer, specifically to the level of the aortic bifurcation. It demonstrates a favorable acute toxicity profile whilst treating large PLN volumes with optimal dose coverage. PMID- 26539523 TI - Using Electronic Health Records to Support Clinical Trials: A Report on Stakeholder Engagement for EHR4CR. AB - BACKGROUND: The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. METHODS: Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. RESULTS: 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. CONCLUSIONS: There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform. PMID- 26539524 TI - Prognostic Significance of NT-proBNP Levels in Patients over 65 Presenting Acute Myocardial Infarction Treated Invasively or Conservatively. AB - OBJECTIVES: Assessment of prognostic significance of NT-proBNP level and the effects of invasive (I) and conservative (C) treatment of acute myocardial infarction (AMI) in patients over 65. MATERIALS AND METHODS: One-year survival was assessed in 286 consecutive patients with AMI aged 65-100 (79 +/- 8) subjected to I or C treatment (136 and 150 individuals), respectively. RESULTS: 245 (85%) patients survived in-hospital stay: 124 (91.1%) received I treatment and 121 (80.6%) received C treatment. Heart failure (HF) was diagnosed in 30 patients receiving I treatment (22.6%) and in 71 subjected to C treatment (47.3%), p < 0,0001. NT-proBNP levels in the latter group were significantly higher than in the 185 patients without HF (12311 +/- 13560 pg/mL versus 4773 +/- 8807 pg/mL, p < 0.0001). NT-proBNP levels after coronary angioplasty were lower than in patients receiving C treatment (5922 +/- 10250 pg/mL versus 8718 +/- 12024 pg/mL, p = 0.0002). Left ventricular ejection fraction was significantly higher in I patients than in C patients (47 +/- 13% versus 42 +/- 11.6%, p = 0.004). During the one-year follow-up, 82.3% of I patients and 61.2% of the C patients survived (p < 0.0003). There was a significantly lower probability of death at NT-proBNP below 8548.5 pg/mL. CONCLUSIONS: The NT-proBNP level in the first day of AMI is a good prognosticator. One-year follow-up prognosis for patients who received I treatment in the AMI is better than that for C patients. I patients exhibit superior left ventricular function after angioplasty and in the follow-up. PMID- 26539525 TI - User Satisfaction Evaluation of the EHR4CR Query Builder: A Multisite Patient Count Cohort System. AB - The Electronic Health Records for Clinical Research (EHR4CR) project aims to develop services and technology for the leverage reuse of Electronic Health Records with the purpose of improving the efficiency of clinical research processes. A pilot program was implemented to generate evidence of the value of using the EHR4CR platform. The user acceptance of the platform is a key success factor in driving the adoption of the EHR4CR platform; thus, it was decided to evaluate the user satisfaction. In this paper, we present the results of a user satisfaction evaluation for the EHR4CR multisite patient count cohort system. This study examined the ability of testers (n = 22 and n = 16 from 5 countries) to perform three main tasks (around 20 minutes per task), after a 30-minute period of self-training. The System Usability Scale score obtained was 55.83 (SD: 15.37), indicating a moderate user satisfaction. The responses to an additional satisfaction questionnaire were positive about the design of the interface and the required procedure to design a query. Nevertheless, the most complex of the three tasks proposed in this test was rated as difficult, indicating a need to improve the system regarding complicated queries. PMID- 26539526 TI - A Pilot Comparative Study of 26 Biochemical Markers in Seminal Plasma and Serum in Infertile Men. AB - INTRODUCTION: The relationships of the biochemical components in seminal plasma and serum, and their origins and physiological effects in male reproductive system have been poorly understood. METHODS: Based on the calibration and quality control measures, 26 biochemical markers, in seminal plasma and serum samples from 36 male infertility patients with nonazoospermia were detected and compared. RESULTS: Only PA was undetectable in all seminal plasma samples. There were significant differences of all other 24 biochemical markers in seminal plasma and serum (P < 0.05) except for UA (P = 0.214). There were rich proteins in seminal plasma, and globulin accounted for about 90%. There were also abundant enzymes in seminal plasma, and the activities of ALT, AST, AKP, GGT, LDH, CK, and alphaHBDH in seminal plasma were significantly higher than those in serum while ADA was inversely lower. There were relatively low levels of Glu, TG, TC, and hsCRP in seminal plasma, but Glu was undetectable in 8 of 36 cases. CONCLUSIONS: The differences of the levels of biochemical markers in seminal plasma and serum might be associated with the selective secretion of testis, epididymis and male accessory glands, and the specific environment needed for sperm metabolism and function maintenance. PMID- 26539527 TI - Survival of Unstressed and Acid-, Cold-, and Starvation-Stress-Adapted Listeria monocytogenes in Ham Extract with Hops Beta Acids and Consumer Acceptability of HBA on Ready-to-Eat Ham. AB - The efficacy of hops beta acids (HBA) against unstressed and stress-adapted Listeria monocytogenes in ham extract and the consumers' acceptability of HBA on ready-to-eat (RTE) hams were investigated. Unstressed or acid-, cold-, or starvation-stress-adapted L. monocytogenes was inoculated (1.3-1.5 log CFU/mL) into 10% ham extract, without (control) or with HBA (4.44 or 10.0 ug/mL). Survival/growth of the pathogen during storage (7.2 degrees C, 26 days) was monitored periodically. Sensory evaluation (30 participants, 9-point hedonic scale) was performed with hams dipped into 0.05, 0.11, and 0.23% HBA solution. Ham extracts without HBA supported rapid growth of unstressed and stress-adapted cells with growth rates of 0.39-0.71 log CFU/mL/day and lag phases of 0-3.26 days. HBA inhibited growth of unstressed L. monocytogenes by slowing (P < 0.05) growth rate (0.24-0.29 log CFU/mL/day) and increasing (P < 0.05) length of the lag phase (3.49-12.98 days) compared to control. Acid-, cold-, or starvation stress-adapted cells showed cross protection against HBA with greater (P < 0.05) growth rates (0.44-0.66 log CFU/mL/day) and similar or shorter lag phases (0-5.44 days) than unstressed cells. HBA did not (P > 0.05) affect sensory attributes of RTE ham. These results are useful for RTE meat processors to develop operational protocols using HBA to control L. monocytogenes. PMID- 26539528 TI - Cortical Structural Connectivity Alterations in Primary Insomnia: Insights from MRI-Based Morphometric Correlation Analysis. AB - The etiology and maintenance of insomnia are proposed to be associated with increased cognitive and physiological arousal caused by acute stressors and associated cognitive rumination. A core feature of such hyperarousal theory of insomnia involves increased sensory processing that interferes with the onset and maintenance of sleep. In this work, we collected structural magnetic resonance imaging data from 35 patients with primary insomnia and 35 normal sleepers and applied structural covariance analysis to investigate whether insomnia is associated with disruptions in structural brain networks centered at the sensory regions (primary visual, primary auditory, and olfactory cortex). As expected, insomnia patients showed increased structural covariance in cortical thickness between sensory and motor regions. We also observed trends of increased covariance between sensory regions and the default-mode network, and the salience network regions, and trends of decreased covariance between sensory regions and the frontoparietal working memory network regions, in insomnia patients. The observed changes in structural covariance tended to correlated with poor sleep quality. Our findings support previous functional neuroimaging studies and provide novel insights into variations in brain network configuration that may be involved in the pathophysiology of insomnia. PMID- 26539529 TI - Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions. AB - The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n = 43) and malignant (n = 44) lesions and was statistically analyzed with clinicopathological parameters, follicular cells' proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA) staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0010 and p = 0.0005, resp.). Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p = 0.0097 and p = 0.0110, resp.). In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p = 0.0301). Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p = 0.1165), lymphatic (p = 0.1989), and vascular invasion (p = 0.0555), as well as in those with increased risk of recurrence rate (p = 0.1165), at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia. PMID- 26539530 TI - How to Choose In Vitro Systems to Predict In Vivo Drug Clearance: A System Pharmacology Perspective. AB - The use of in vitro metabolism data to predict human clearance has become more significant in the current prediction of large scale drug clearance for all the drugs. The relevant information (in vitro metabolism data and in vivo human clearance values) of thirty-five drugs that satisfied the entry criteria of probe drugs was collated from the literature. Then the performance of different in vitro systems including Escherichia coli system, yeast system, lymphoblastoid system and baculovirus system is compared after in vitro-in vivo extrapolation. Baculovirus system, which can provide most of the data, has almost equal accuracy as the other systems in predicting clearance. And in most cases, baculovirus system has the smaller CV in scaling factors. Therefore, the baculovirus system can be recognized as the suitable system for the large scale drug clearance prediction. PMID- 26539531 TI - Development of the 1.2 T~1.5 T Permanent Magnetic Resonance Imaging Device and Its Application for Mouse Imaging. AB - By improving the main magnet, gradient, and RF coils design technology, manufacturing methods, and inventing new magnetic resonance imaging (MRI) special alloy, a cost-effective and small animal specific permanent magnet-type three dimensional magnetic resonance imager was developed. The main magnetic field strength of magnetic resonance imager with independent intellectual property rights is 1.2~1.5 T. To demonstrate its effectiveness and validate the mouse imaging experiments in different directions, we compared the images obtained by small animal specific permanent magnet-type three-dimensional magnetic resonance imager with that obtained by using superconductor magnetic resonance imager for clinical diagnosis. PMID- 26539532 TI - Attenuation of Upper Body Accelerations during Gait: Piloting an Innovative Assessment Tool for Parkinson's Disease. AB - The objective of the current investigation was to explore whether upper body accelerations obtained during gait provide sensitive measures of postural control in people with Parkinson's disease (PD). Thirteen people with PD (70 +/- 11 years) and nineteen age-matched controls (70 +/- 7 years) walked continuously for two minutes while wearing three inertial sensors located on their lower back (L5), shoulder level (C7), and head. Magnitude (root mean square (RMS)), attenuation (attenuation coefficient), and smoothness (Harmonic ratios, HR) of the accelerations were calculated. People with PD demonstrated greater RMS, particularly in the mediolateral direction, but similar harmonic ratio of head accelerations compared to controls. In addition, they did not attenuate accelerations through the trunk and neck as well as control participants. Our findings indicate that measuring upper body movement provides unique information regarding postural control in PD and that poor attenuation of acceleration from the pelvis to the head contributes to impaired head control. This information is simple to measure and appears to be sensitive to PD and, consequently, is proposed to benefit researchers and clinicians. PMID- 26539533 TI - Medication Lists and Brown Bag Reviews: Potential Positive and Negative Impacts on Patients Beliefs about Their Medicine. AB - INTRODUCTION: Medication lists and structured medication counselling (SMC) including "brown bag reviews" (BBR) are important instruments for medication safety. The aim of this study was to explore whether patients' use of a medication list is associated with their beliefs about their medicine and their memory of SMC. METHODS: Baseline data of 344 patients enrolled into the "Polypharmacy in Multimorbid Patients study" were analysed. Linear regression models were calculated for the "specific necessity subscale" (SNS) and the "specific concerns subscale" (SCS) of the German "Beliefs About Medicine Questionnaire," including self-developed variables assessing patients' use of a medication list, their memory of SMC, and sociodemographic data. RESULTS: 62.8% (n = 216) remembered an appointment for SMC and 32.0% (n = 110) BBR. The SNS correlated positively with regular receipt of a medication list (beta = 0.286, p < 0.01) and negatively with memory of a BBR (beta = -0.268; p < 0.01). The SCS correlated positively with memory of a BBR (beta = 0.160, p = 0.02) and negatively with the comprehensiveness of the mediation list (beta = -0.224; p < 0.01). CONCLUSIONS: A comprehensive medication list may reduce patients' concerns and increase the perceived necessity of their medication. A potential negative impact of BBR on patients' beliefs about their medicine should be considered and quality standards for SMC developed. PMID- 26539534 TI - PPARalpha Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia Reperfusion Injury. AB - Ischemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor alpha (PPARalpha) has been related with positive effects on IRI. In addition, the deacetylase enzyme sirtuin 1 (SIRT1) has recently emerged as a promising target for preventing IRI, through its interaction with stress-related mechanisms, such as endoplasmic reticulum stress (ERS). Taking this into account, this study aims to explore whether PPARalpha agonist WY-14643 could protect steatotic livers against IRI through sirtuins and ERS signaling pathway. Obese Zucker rats were pretreated or not pretreated with WY-14643 (10 mg/kg intravenously) and then submitted to partial (70%) hepatic ischemia (1 hour) followed by 24 hours of reperfusion. Liver injury (ALT levels), lipid peroxidation (MDA), SIRT1 activity, and the protein expression of SIRT1 and SIRT3 and ERS parameters (IRE1alpha, peIF2, caspase 12, and CHOP) were evaluated. Treatment with WY-14643 reduced liver injury in fatty livers, enhanced SIRT1 activity, and prevented ERS. Together, our results indicated that PPARalpha agonist WY-14643 may exert its protective effect in fatty livers, at least in part, via SIRT1 induction and ERS prevention. PMID- 26539535 TI - Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography. AB - The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID- 26539536 TI - Salmonella Typhimurium and Salmonella Sofia: Growth in and Persistence on Eggs under Production and Retail Conditions. AB - Salmonellosis in Australia has been linked to eggs and egg products with specific serotypes associated with outbreaks. We compared attachment to and survival on egg shells and growth in eggs of two Salmonella serotypes, an egg outbreak associated Salmonella Typhimurium and a non-egg-associated Salmonella enterica ssp. II 1,4,12,27:b:[e,n,x] (S. Sofia). Experiments were conducted at combinations of 4, 15, 22, 37 and 42 degrees C. No significant differences occurred between the serotypes in maximum growth rates, which were significantly greater (P < 0.001) in egg yolk (0.427 log10 CFU/mL/h) compared to whole egg (0.312 log10 CFU/mL/h) and egg white (0.029 log10 CFU/mL/h). Attachment to egg shells varied by time (1 or 20 min) and temperature (4, 22 and 42 degrees C), with S. Typhimurium isolates attaching at higher levels (P < 0.05) than S. Sofia after 1 min at 4 degrees C and S. Typhimurium ATCC 14028 attaching at higher (P < 0.05) levels at 22 degrees C. Survival on egg shells was not significantly different across isolates. Salmonella serotypes behaved similarly regarding growth in egg contents, attachment to egg shells and survival on eggs, indicating that other factors more likely contributed to reasons for S. Typhimurium being implicated in multiple egg-associated outbreaks. PMID- 26539537 TI - Modeling the Generation of Phase-Amplitude Coupling in Cortical Circuits: From Detailed Networks to Neural Mass Models. AB - Phase-amplitude coupling (PAC), the phenomenon where the amplitude of a high frequency oscillation is modulated by the phase of a lower frequency oscillation, is attracting an increasing interest in the neuroscience community due to its potential relevance for understanding healthy and pathological information processing in the brain. PAC is a diverse phenomenon, having been experimentally detected in at least ten combinations of rhythms: delta-theta, delta-alpha, delta beta, delta-gamma, theta-alpha, theta-beta, theta-gamma, alpha-beta, alpha-gamma, and beta-gamma. However, a complete understanding of the biophysical mechanisms generating this diversity is lacking. Here we review computational models of PAC generation that range from detailed models of neuronal networks, where each cell is described by Hodgkin-Huxley-type equations, to neural mass models (NMMs) where only the average activities of neuronal populations are considered. We argue that NMMs are an appropriate mathematical framework (due to the small number of parameters and variables involved and the richness of the dynamics they can generate) to study the PAC phenomenon. PMID- 26539538 TI - Robot-Assisted Laparoscopic Nephroureterectomy versus Hand-Assisted Laparoscopic Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: A Matched Comparison Study. AB - OBJECTIVES: To investigate the perioperative and oncological outcomes of hand assisted laparoscopic nephroureterectomy (HANU) and robotic-assisted nephroureterectomy (RANU). METHODS: Patients who underwent RANU were matched by sex, age (+/- 5 years), and tumor location to those who underwent HANU; 18 matched pairs were included. RESULTS: Each group consisted of five men and 13 women. The mean age was 70.4 years in RANU group and 69.6 years in HANU group (p = 0.646). Each group contained 10 patients with tumor location in the renal pelvis, five in the ureter, and three in both sites. The median follow-up time was 6.1 months for the RANU group and 47.8 months for the HANU group. The demographic and pathological data did not differ significantly. The RANU group had significantly less blood loss (p < 0.001), resumed oral intake earlier (p = 0.043), and had shorter hospital stays (p = 0.014) but higher pain scores associated with their wounds (p = 0.043). The oncological outcomes were comparable with those of the HANU group. CONCLUSIONS: Our results show that the RANU and HANU groups have comparable operative, early postoperative, and functional outcomes. A longer follow-up period would be needed for final comparison of oncological outcome. PMID- 26539539 TI - Coexpression Network Analysis of miRNA-142 Overexpression in Neuronal Cells. AB - MicroRNAs are small noncoding RNA molecules, which are differentially expressed in diverse biological processes and are also involved in the regulation of multiple genes. A number of sites in the 3' untranslated regions (UTRs) of different mRNAs allow complimentary binding for a microRNA, leading to their posttranscriptional regulation. The miRNA-142 is one of the microRNAs overexpressed in neurons that is found to regulate SIRT1 and MAOA genes. Differential analysis of gene expression data, which is focused on identifying up or downregulated genes, ignores many relationships between genes affected by miRNA-142 overexpression in a cell. Thus, we applied a correlation network model to identify the coexpressed genes and to study the impact of miRNA-142 overexpression on this network. Combining multiple sources of knowledge is useful to infer meaningful relationships in systems biology. We applied coexpression model on the data obtained from wild type and miR-142 overexpression neuronal cells and integrated miRNA seed sequence mapping information to identify genes greatly affected by this overexpression. Larger differences in the enriched networks revealed that the nervous system development related genes such as TEAD2, PLEKHA6, and POGLUT1 were greatly impacted due to miRNA-142 overexpression. PMID- 26539540 TI - Bayesian Estimation of the True Prevalence and of the Diagnostic Test Sensitivity and Specificity of Enteropathogenic Yersinia in Finnish Pig Serum Samples. AB - Bayesian analysis was used to estimate the pig's and herd's true prevalence of enteropathogenic Yersinia in serum samples collected from Finnish pig farms. The sensitivity and specificity of the diagnostic test were also estimated for the commercially available ELISA which is used for antibody detection against enteropathogenic Yersinia. The Bayesian analysis was performed in two steps; the first step estimated the prior true prevalence of enteropathogenic Yersinia with data obtained from a systematic review of the literature. In the second step, data of the apparent prevalence (cross-sectional study data), prior true prevalence (first step), and estimated sensitivity and specificity of the diagnostic methods were used for building the Bayesian model. The true prevalence of Yersinia in slaughter-age pigs was 67.5% (95% PI 63.2-70.9). The true prevalence of Yersinia in sows was 74.0% (95% PI 57.3-82.4). The estimates of sensitivity and specificity values of the ELISA were 79.5% and 96.9%. PMID- 26539541 TI - Analysis of Requirements for the Medication Profile to Be Used in Clinical Research: Protocol Feasibility Studies and Patient Recruitment. AB - A "Medication Profile," the information about the medicines a person is using and has used, is a core part of many electronic health record systems and summaries. However, there is little objective research into the data elements that the profile should contain to support the uses it must serve. With the increasing emphasis on secondary uses of electronic health information, as well as supporting the requirements to support direct to patient care, the Medication Profile should also support the requirements from clinical research. However, there is little, if any, description of these available. This paper describes an analysis of a set of study eligibility criteria that was undertaken to investigate which medication-related data elements would be required to support two clinical research use cases: the parameters to query a patient's Medication Profile to assess their suitability for entry into a trial (patient recruitment) and the parameters to query a set of Medication Profiles in a data warehouse to assess whether the eligibility criteria as described would yield a reasonable cohort of patients as potential subjects (protocol feasibility). These medication related data elements then become information requirements that a Medication Profile should ideally meet, in order to be able to support these two uses in the clinical research domain. PMID- 26539542 TI - Implantation of 3D-Printed Patient-Specific Aneurysm Models into Cadaveric Specimens: A New Training Paradigm to Allow for Improvements in Cerebrovascular Surgery and Research. AB - AIM: To evaluate the feasibility of implanting 3D-printed brain aneurysm model in human cadavers and to assess their utility in neurosurgical research, complex case management/planning, and operative training. METHODS: Two 3D-printed aneurysm models, basilar apex and middle cerebral artery, were generated and implanted in four cadaveric specimens. The aneurysms were implanted at the same anatomical region as the modeled patient. Pterional and orbitozygomatic approaches were done on each specimen. The aneurysm implant, manipulation capabilities, and surgical clipping were evaluated. RESULTS: The 3D aneurysm models were successfully implanted to the cadaveric specimens' arterial circulation in all cases. The features of the neck in terms of flexibility and its relationship with other arterial branches allowed for the practice of surgical maneuvering characteristic to aneurysm clipping. Furthermore, the relationship of the aneurysm dome with the surrounding structures allowed for better understanding of the aneurysmal local mass effect. Noticeably, all of these observations were done in a realistic environment provided by our customized embalming model for neurosurgical simulation. CONCLUSION: 3D aneurysms models implanted in cadaveric specimens may represent an untapped training method for replicating clip technique; for practicing certain approaches to aneurysms specific to a particular patient; and for improving neurosurgical research. PMID- 26539543 TI - Contribution of Electronic Medical Records to the Management of Rare Diseases. AB - PURPOSE: Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR) in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients' data with ophthalmology-specific EMR. METHODS: Ophthalmology-specific EMR software (Softalmo software Corilus) was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. RESULTS: A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. DISCUSSION: EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. CONCLUSION: Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease. PMID- 26539544 TI - Reliability of Force-Velocity Tests in Cycling and Cranking Exercises in Men and Women. AB - The present study examined the reliability of the force-velocity relationship during cycling and arm cranking exercises in active males and females. Twenty male and seventeen female physical education students performed three-session tests with legs and three-session tests with arms on a friction-loaded ergometer on six different sessions in a randomized order. The reliability of maximal power (Pmax), maximal pedal rate (V 0), and maximal force (F0) were studied using the coefficient of variation (CV), the intraclass correlation coefficient (ICC) and the test-retest correlation coefficient (r). Reliability indices were better for men (1.74 <= CV <= 4.36, 0.82 <= ICC <= 0.97, and 0.81 <= r <= 0.97) compared with women (2.34 <= CV <= 7.04, 0.44 <= ICC <= 0.98, and 0.44 <= r <= 0.98) and in cycling exercise (1.74 <= CV <= 3.85, 0.88 <= ICC <= 0.98, and 0.90 <= r <= 0.98) compared with arm exercise (2.37 <= CV <= 7.04, 0.44 <= ICC <= 0.95, and 0.44 <= r <= 0.95). Furthermore, the reliability indices were high for Pmax and F0 whatever the expression of the results (raw data or data related to body dimensions). Pmax and F0 could be used in longitudinal physical fitness investigations. However, further studies are needed to judge V 0 reliability. PMID- 26539545 TI - From Cerebellar Activation and Connectivity to Cognition: A Review of the Quadrato Motor Training. AB - The importance of the cerebellum is increasingly recognized, not only in motor control but also in cognitive learning and function. Nevertheless, the relationship between training-induced cerebellar activation and electrophysiological and structural changes in humans has yet to be established. In the current paper, we suggest a general model tying cerebellar function to cognitive improvement, via neuronal synchronization, as well as biochemical and anatomical changes. We then suggest that sensorimotor training provides an optimal paradigm to test the proposed model and review supporting evidence of Quadrato Motor Training (QMT), a sensorimotor training aimed at increasing attention and coordination. Subsequently, we discuss the possible mechanisms through which QMT may exert its beneficial effects on cognition (e.g., increased creativity, reflectivity, and reading), focusing on cerebellar alpha activity as a possible mediating mechanism allowing cognitive improvement, molecular and anatomical changes. Using the example of QMT research, this paper emphasizes the importance of investigating whole-body sensorimotor training paradigms utilizing a multidisciplinary approach and its implications to healthy brain development. PMID- 26539546 TI - Genetic Diversity and Incidence of Virulence-Associated Genes of Arcobacter butzleri and Arcobacter cryaerophilus Isolates from Pork, Beef, and Chicken Meat in Poland. AB - Incidence of 9 virulence-associated genes and genetic diversity was determined in 79 A. butzleri and 6 A. cryaerophilus isolates from pork, beef, and chicken meat. All A. butzleri isolates harboured the tlyA gene, and most of them carried ciaB, mviN, pldA, cadF, and cj1349 genes. ciaB was found to occur with higher frequency in poultry if compared with pork (p = 0.0007), while irgA was more frequent in poultry than in beef (p = 0.007). All 6 A. cryaerophilus isolates harboured the ciaB gene, while mviN and tlyA were detected in 3 out of these isolates. Only one isolate carried the cadF gene. All beef-derived A. cryaerophilus isolates carried ciaB, mviN, and tlyA genes. A. cryaerophilus isolates from chicken meat harboured ciaB gene only. The pork-derived isolate harboured ciaB and cadF genes. Seventy four genotypes were distinguished within 79 A. butzleri isolates. Nineteen from 21 isolates derived from beef and pork were found to be closely related to A. butzleri from chicken meat. Each of the 6 A. cryaerophilus isolates was found to have unique genotype. We demonstrated that closely related genotypes can spread within pork, beef, and chicken meat populations of A. butzleri but not A. cryaerophilus. PMID- 26539547 TI - Translational Medicine and Patient Safety in Europe: TRANSFoRm--Architecture for the Learning Health System in Europe. AB - The Learning Health System (LHS) describes linking routine healthcare systems directly with both research translation and knowledge translation as an extension of the evidence-based medicine paradigm, taking advantage of the ubiquitous use of electronic health record (EHR) systems. TRANSFoRm is an EU FP7 project that seeks to develop an infrastructure for the LHS in European primary care. METHODS: The project is based on three clinical use cases, a genotype-phenotype study in diabetes, a randomised controlled trial with gastroesophageal reflux disease, and a diagnostic decision support system for chest pain, abdominal pain, and shortness of breath. RESULTS: Four models were developed (clinical research, clinical data, provenance, and diagnosis) that form the basis of the projects approach to interoperability. These models are maintained as ontologies with binding of terms to define precise data elements. CDISC ODM and SDM standards are extended using an archetype approach to enable a two-level model of individual data elements, representing both research content and clinical content. Separate configurations of the TRANSFoRm tools serve each use case. CONCLUSIONS: The project has been successful in using ontologies and archetypes to develop a highly flexible solution to the problem of heterogeneity of data sources presented by the LHS. PMID- 26539548 TI - Amylose-Based Cationic Star Polymers for siRNA Delivery. AB - A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials. PMID- 26539549 TI - Open Partial Nephrectomy for High-Risk Renal Masses Is Associated with Renal Pseudoaneurysms: Assessment of a Severe Procedure-Related Complication. AB - OBJECTIVES: A symptomatic renal pseudoaneurysm (RPA) is a severe complication after open partial nephrectomy (OPN). The aim of our study was to assess incidence and risk factors for RPA formation. Furthermore, we present our management strategy. PATIENTS AND METHODS: Clinical records of consecutive patients undergoing OPN were assessed for surgical outcome and postoperative complications. Renal masses were risk stratified for tumor complexity according to the PADUA score. Uni- and multivariate analysis for symptomatic RPAs were performed using the t-tests and logistic regression. RESULTS: We identified 233 patients treated with OPN. Symptomatic RPAs were observed in 13 (5.6%) patients, on average 14 (4-42) days after surgery. Uni- and multivariate analysis identified tumor complexity to be an independent predictor for symptomatic RPAs (p = 0.004). There was a significant correlation between RPAs and transfusion and the duration of stay (p < 0.001 and p = 0.021). Symptomatic RPAs were diagnosed with CT scans and successfully treated with arterial embolization. DISCUSSION: Symptomatic RPAs are not uncommon after OPN for high-risk renal masses. A high nephrometry score is a predictor for this severe complication and may enable a risk-stratified followup. RPAs can successfully be located by CT angiography, which enables targeted angiographic treatment. PMID- 26539550 TI - Relation between the Sensory and Anthropometric Variables in the Quiet Standing Postural Control: Is the Inverted Pendulum Important for the Static Balance Control? AB - The aim of this study was to evaluate the relation between the sensory and anthropometric variables in the quiet standing. METHODS: One hundred individuals (50 men, 50 women; 20-40 years old) participated in this study. For all participants, the body composition (fat tissue, lean mass, bone mineral content, and bone mineral density) and body mass, height, trunk-head length, lower limb length, and upper limb length were measured. The center of pressure was measured during the quiet standing posture, the eyes opened and closed with a force platform. Correlation and regression analysis were run to analyze the relation among body composition, anthropometric data, and postural sway. RESULTS: The correlation analysis showed low relation between postural sway and anthropometric variables. The multiple linear regression analyses showed that the height explained 12% of the mediolateral displacement and 11% of the center of pressure area. The length of the trunk head explained 6% of displacement in the anteroposterior postural sway. During eyes closed condition, the support basis and height explained 18% of mediolateral postural sway. CONCLUSION: The postural control depends on body composition and dimension. This relation is mediated by the sensory information. The height was the anthropometric variable that most influenced the postural sway. PMID- 26539551 TI - Regular Chinese Green Tea Consumption is Protective for Diabetic Retinopathy: A Clinic-Based Case-Control Study. AB - OBJECTIVE: To determine the association between regular Chinese green tea consumption and the risk of diabetic retinopathy (DR) in diabetic patients in China. METHODS: 100 DR patients and 100 age-sex-matched diabetic controls without retinopathy were recruited in a clinic-based, case-control study. DR was defined from retinal photographs and detailed information on Chinese green tea consumption of the participants was collected through a face-to-face interview. RESULTS: The crude odds ratio [OR] of Chinese green tea consumption for DR was 0.49 (95% confidence interval: 0.26-0.90). When stratified by sex, the protective effect of Chinese green tea consumption on DR was statistically significant in women (P = 0.01) but not in men (P = 0.63). After adjusting for age, sex, and other confounders, DR was significantly associated with Chinese green tea consumption (OR = 0.48; P = 0.04), higher systolic blood pressure (OR = 1.02; P = 0.05), longer duration of diabetes (OR = 1.07; P = 0.02), and the presence of family history of diabetes (OR = 2.35; P = 0.04). CONCLUSIONS: Diabetic patients who had regularly drunk Chinese green tea every week for at least one year in their lives had a DR risk reduction of about 50% compared with those who had not. Regular Chinese green tea consumption may be a novel approach for the prevention of DR. PMID- 26539552 TI - Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA. AB - We conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D). We analyzed 415 families (2,008 individuals) previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For retinopathy, two linkage peaks were mapped: one located at the HLA region and another novel locus telomeric to HLA. For nephropathy, a linkage peak centromeric to HLA was mapped, but the linkage peak telomeric to HLA seen in retinopathy was absent. Because of the strong association of T1D with DRB1*03:01 and DRB1*04:01, we stratified our analyses based on families whose probands were positive for DRB1*03:01 or DRB1*04:01. When analyzing the DRB1*03:01-positive retinopathy families, in addition to the novel telomeric locus, one centromeric to HLA was identified at the same location as the nephropathy peak. When we stratified on DRB1*04:01-positive families, the HLA telomeric peak strengthened but the centromeric peak disappeared. Our findings showed that HLA and non-HLA loci on chromosome 6 are involved in T1D complications' expression. While the HLA region is a major contributor to the expression of T1D, our results suggest an interaction between specific HLA alleles and other loci that influence complications' expression. PMID- 26539553 TI - Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri. AB - The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts. PMID- 26539554 TI - Phase II Study of Personalized Peptide Vaccination with Both a Hepatitis C Virus Derived Peptide and Peptides from Tumor-Associated Antigens for the Treatment of HCV-Positive Advanced Hepatocellular Carcinoma Patients. AB - Objective. To evaluate safety and immune responses of personalized peptide vaccination (PPV) for hepatitis C virus- (HCV-) positive advanced hepatocellular carcinoma (HCC). Patients and Methods. Patients diagnosed with HCV-positive advanced HCC were eligible for this study. A maximum of four HLA-matched peptides were selected based on the preexisting IgG responses specific to 32 different peptides, which consisted of a single HCV-derived peptide at core protein positions 35-44 (C-35) and 31 peptides derived from 15 different tumor-associated antigens (TAAs), followed by subcutaneous administration once per week for 8 weeks. Peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses were measured before and after vaccination. Results. Forty-two patients were enrolled. Grade 3 injection site skin reaction was observed in 2 patients, but no other PPV related severe adverse events were noted. Peptide-specific CTL responses before vaccination were observed in only 3 of 42 patients, but they became detectable in 23 of 36 patients tested after vaccination. Peptide-specific IgG responses were also boosted in 19 of 36 patients. Peptide-specific IgG1 responses to both C-35 and TAA-derived peptides could be potentially prognostic for overall survival. Conclusion. Further clinical study of PPV would be warranted for HCV-positive advanced HCC, based on the safety and strong immune induction. PMID- 26539555 TI - Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer. AB - Using carbohydrate microarrays, we explored potential natural ligands of antitumor monoclonal antibody HAE3. This antibody was raised against a murine mammary tumor antigen but was found to cross-react with a number of human epithelial tumors in tissues. Our carbohydrate microarray analysis reveals that HAE3 is specific for an O-glycan cryptic epitope that is normally hidden in the cores of blood group substances. Using HAE3 to screen tumor cell surface markers by flow cytometry, we found that the HAE3 glycoepitope, gp(HAE3), was highly expressed by a number of human breast cancer cell lines, including some triple negative cancers that lack the estrogen, progesterone, and Her2/neu receptors. Taken together, we demonstrate that HAE3 recognizes a conserved cryptic glycoepitope of blood group precursors, which is nevertheless selectively expressed and surface-exposed in certain breast tumor cells. The potential of this class of O-glycan cryptic antigens in breast cancer subtyping and targeted immunotherapy warrants further investigation. PMID- 26539556 TI - Gingiva Equivalents Secrete Negligible Amounts of Key Chemokines Involved in Langerhans Cell Migration Compared to Skin Equivalents. AB - Both oral mucosa and skin have the capacity to maintain immune homeostasis or regulate immune responses upon environmental assault. Whereas much is known about key innate immune events in skin, little is known about oral mucosa. Comparative studies are limited due to the scarce supply of oral mucosa for ex vivo studies. Therefore, we used organotypic tissue equivalents (reconstructed epithelium on fibroblast-populated collagen hydrogel) to study cross talk between cells. Oral mucosa and skin equivalents were compared regarding secretion of cytokines and chemokines involved in LC migration and general inflammation. Basal secretion, representative of homeostasis, and also secretion after stimulation with TNFalpha, an allergen (cinnamaldehyde), or an irritant (SDS) were assessed. We found that proinflammatory IL-18 and chemokines CCL2, CCL20, and CXCL12, all involved in LC migration, were predominantly secreted by skin as compared to gingiva. Furthermore, CCL27 was predominantly secreted by skin whereas CCL28 was predominantly secreted by gingiva. In contrast, general inflammatory cytokines IL 6 and CXCL8 were secreted similarly by skin and gingiva. These results indicate that the cytokines and chemokines triggering innate immunity and LC migration are different in skin and gingiva. This differential regulation should be figured into novel therapy or vaccination strategies in the context of skin versus mucosa. PMID- 26539557 TI - Gamma Delta (gammadelta) T Cells and Their Involvement in Behcet's Disease. AB - Behcet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (gammadelta) T cells are reported to have a role. gammadelta T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of gammadelta T cells in BD. We review the literature and discuss the roles that gammadelta T cells may play in BD pathogenesis. PMID- 26539558 TI - Experimental Immunization Based on Plasmodium Antigens Isolated by Antibody Affinity. AB - Vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. We used the sera of malaria self resistant ICR mice to lethal Plasmodium yoelii yoelii 17XL for purification of their IgGs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to immunize BALB/c mice. The presence of specific antibodies in vaccinated mice serum was studied by immunoblot analysis at different days after vaccination and showed an intensive immune response to a wide range of antigens with molecular weight ranging between 22 and 250 kDa. The humoral response allowed delay of the infection after the inoculation to high lethal doses of P. yoelii yoelii 17XL resulting in a partial protection against malaria disease, although final survival was managed in a low proportion of challenged mice. This approach shows the potential to prevent malaria disease with a set of antigens isolated from blood-stage parasites. PMID- 26539559 TI - The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria Tetanus Toxoid Vaccine Induced Amyloid beta Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs. AB - The reduction of brain amyloid beta (Abeta) peptides by anti-Abeta antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Abeta peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Abeta antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Abeta antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Abeta 40, and Abeta 42 compared to Abeta fibrils. The levels of serum anti-Abeta antibodies and plasma Abeta peptides increased in both animals and decreased the brain Abeta 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Abeta antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Abeta peptides and their toxic effects via clearance of Abeta peptides by generated antibodies. PMID- 26539560 TI - Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis. AB - Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund's adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund's adjuvant (IFA) 21 days after the first injection. These mice typically develop disease 26 to 35 days after the initial injection. C57BL/6J mice are resistant to arthritis induced by type II bovine collagen, but can develop arthritis when immunized with type II chicken collagen in CFA, and receive a boost of type II chicken collagen in IFA 21 days after the first injection. The concentration of heat-killed Mycobacterium tuberculosis H37RA (MT) in CFA also differs for each strain. DBA/1J mice develop arthritis with 1 mg/ml MT, while C57BL/6J mice require and 3-4 mg/ml MT in order to develop arthritis. CIA develops slowly in C57BL/6J mice and cases of arthritis are mild when compared to DBA/1J mice. This protocol describes immunization of DBA/1J mice with type II bovine collagen and the immunization of C57BL/6J mice with type II chicken collagen. PMID- 26539562 TI - Biosynthesis of a Novel Glutamate Racemase Containing a Site-Specific 7 Hydroxycoumarin Amino Acid: Enzyme-Ligand Promiscuity Revealed at the Atomistic Level. AB - Glutamate racemase (GR) catalyzes the cofactor independent stereoinversion of l- to d-glutamate for biosynthesis of bacterial cell walls. Because of its essential nature, this enzyme is under intense scrutiny as a drug target for the design of novel antimicrobial agents. However, the flexibility of the enzyme has made inhibitor design challenging. Previous steered molecular dynamics (MD), docking, and experimental studies have suggested that the enzyme forms highly varied complexes with different competitive inhibitor scaffolds. The current study employs a mutant orthogonal tRNA/aminoacyl-tRNA synthetase pair to genetically encode a non-natural fluorescent amino acid, l-(7-hydroxycoumarin-4-yl) ethylglycine (7HC), into a region (Tyr53) remote from the active site (previously identified by MD studies as undergoing ligand-associated changes) to generate an active mutant enzyme (GRY53/7HC). The GRY53/7HC enzyme is an active racemase, which permitted us to examine the nature of these idiosyncratic ligand-associated phenomena. One type of competitive inhibitor resulted in a dose-dependent quenching of the fluorescence of GRY53/7HC, while another type of competitive inhibitor resulted in a dose-dependent increase in fluorescence of GRY53/7HC. In order to investigate the environmental changes of the 7HC ring system that are distinctly associated with each of the GRY53/7HC-ligand complexes, and thus the source of the disparate quenching phenomena, a parallel computational study is described, which includes essential dynamics, ensemble docking and MD simulations of the relevant GRY53/7HC-ligand complexes. The changes in the solvent exposure of the 7HC ring system due to ligand-associated GR changes are consistent with the experimentally observed quenching phenomena. This study describes an approach for rationally predicting global protein allostery resulting from enzyme ligation to distinctive inhibitor scaffolds. The implications for fragment-based drug discovery and high throughput screening are discussed. PMID- 26539561 TI - New Frontiers for the NFIL3 bZIP Transcription Factor in Cancer, Metabolism and Beyond. AB - The bZIP transcription factor NFIL3 (Nuclear factor Interleukin 3 regulated, also known as E4 binding protein 4, E4BP4) regulates diverse biological processes from circadian rhythm to cellular viability. Recently, a host of novel roles have been identified for NFIL3 in immunological signal transduction, cancer, aging and metabolism. Elucidating the signaling pathways that are impacted by NFIL3 and the regulatory mechanisms that it targets, inhibits or activates will be critical for developing a clearer picture of its physiological roles in disease and normal processes. This review will discuss the recent advances and emerging issues regarding NFIL3-mediated transcriptional regulation of CEBPbeta and FOXO1 activated genes and signal transduction. PMID- 26539563 TI - Rapid, Multiplexed Phosphoprotein Profiling Using Silicon Photonic Sensor Arrays. AB - Extracellular signaling is commonly mediated through post-translational protein modifications that propagate messages from membrane-bound receptors to ultimately regulate gene expression. Signaling cascades are ubiquitously intertwined, and a full understanding of function can only be gleaned by observing dynamics across multiple key signaling nodes. Importantly, targets within signaling cascades often represent opportunities for therapeutic development or can serve as diagnostic biomarkers. Protein phosphorylation is a particularly important post translational modification that controls many essential cellular signaling pathways. Not surprisingly, aberrant phosphorylation is found in many human diseases, including cancer, and phosphoprotein-based biomarker signatures hold unrealized promise for disease monitoring. Moreover, phosphoprotein analysis has wide-ranging applications across fundamental chemical biology, as many drug discovery efforts seek to target nodes within kinase signaling pathways. For both fundamental and translational applications, the analysis of phosphoprotein biomarker targets is limited by a reliance on labor-intensive and/or technically challenging methods, particularly when considering the simultaneous monitoring of multiplexed panels of phosphoprotein biomarkers. We have developed a technology based upon arrays of silicon photonic microring resonator sensors that fills this void, facilitating the rapid and automated analysis of multiple phosphoprotein levels from both cell lines and primary human tumor samples requiring only minimal sample preparation. PMID- 26539565 TI - iShadow: Design of a Wearable, Real-Time Mobile Gaze Tracker. AB - Continuous, real-time tracking of eye gaze is valuable in a variety of scenarios including hands-free interaction with the physical world, detection of unsafe behaviors, leveraging visual context for advertising, life logging, and others. While eye tracking is commonly used in clinical trials and user studies, it has not bridged the gap to everyday consumer use. The challenge is that a real-time eye tracker is a power-hungry and computation-intensive device which requires continuous sensing of the eye using an imager running at many tens of frames per second, and continuous processing of the image stream using sophisticated gaze estimation algorithms. Our key contribution is the design of an eye tracker that dramatically reduces the sensing and computation needs for eye tracking, thereby achieving orders of magnitude reductions in power consumption and form-factor. The key idea is that eye images are extremely redundant, therefore we can estimate gaze by using a small subset of carefully chosen pixels per frame. We instantiate this idea in a prototype hardware platform equipped with a low-power image sensor that provides random access to pixel values, a low-power ARM Cortex M3 microcontroller, and a bluetooth radio to communicate with a mobile phone. The sparse pixel-based gaze estimation algorithm is a multi-layer neural network learned using a state-of-the-art sparsity-inducing regularization function that minimizes the gaze prediction error while simultaneously minimizing the number of pixels used. Our results show that we can operate at roughly 70mW of power, while continuously estimating eye gaze at the rate of 30 Hz with errors of roughly 3 degrees. PMID- 26539564 TI - TIM-3, a Possible Target for Immunotherapy in Cancer and Chronic Viral Infections. AB - Effector T-cell responses are controlled by complex mechanisms involving various soluble factors and co-stimulatory and co-inhibitory molecules. These inhibitory receptors act as immune checkpoints and are extensively investigated as possible therapeutic targets, such as PD-1 and CTLA-4. Recently TIM-3 is also gaining prominence in tumor and chronic viral infection models as a candidate for immunotherapy in conjunction with other inhibitory receptors. This review discusses the recent findings on the expression of TIM-3 and its ligand in tumor and chronic viral infection. PMID- 26539566 TI - Visualization of Time-Series Sensor Data to Inform the Design of Just-In-Time Adaptive Stress Interventions. AB - We investigate needs, challenges, and opportunities in visualizing time-series sensor data on stress to inform the design of just-in-time adaptive interventions (JITAIs). We identify seven key challenges: massive volume and variety of data, complexity in identifying stressors, scalability of space, multifaceted relationship between stress and time, a need for representation at multiple granularities, interperson variability, and limited understanding of JITAI design requirements due to its novelty. We propose four new visualizations based on one million minutes of sensor data (n=70). We evaluate our visualizations with stress researchers (n=6) to gain first insights into its usability and usefulness in JITAI design. Our results indicate that spatio-temporal visualizations help identify and explain between- and within-person variability in stress patterns and contextual visualizations enable decisions regarding the timing, content, and modality of intervention. Interestingly, a granular representation is considered informative but noise-prone; an abstract representation is the preferred starting point for designing JITAIs. PMID- 26539567 TI - Is Multi-model Feature Matching Better for Endoscopic Motion Estimation? AB - Camera motion estimation is a standard yet critical step to endoscopic visualization. It is affected by the variation of locations and correspondences of features detected in 2D images. Feature detectors and descriptors vary, though one of the most widely used remains SIFT. Practitioners usually also adopt its feature matching strategy, which defines inliers as the feature pairs subjecting to a global affine transformation. However, for endoscopic videos, we are curious if it is more suitable to cluster features into multiple groups. We can still enforce the same transformation as in SIFT within each group. Such a multi-model idea has been recently examined in the Multi-Affine work, which outperforms Lowe's SIFT in terms of re-projection error on minimally invasive endoscopic images with manually labelled ground-truth matches of SIFT features. Since their difference lies in matching, the accuracy gain of estimated motion is attributed to the holistic Multi-Affine feature matching algorithm. But, more concretely, the matching criterion and point searching can be the same as those built in SIFT. We argue that the real variation is only the motion model verification. We either enforce a single global motion model or employ a group of multiple local ones. In this paper, we investigate how sensitive the estimated motion is affected by the number of motion models assumed in feature matching. While the sensitivity can be analytically evaluated, we present an empirical analysis in a leaving-one-out cross validation setting without requiring labels of ground-truth matches. Then, the sensitivity is characterized by the variance of a sequence of motion estimates. We present a series of quantitative comparison such as accuracy and variance between Multi-Affine motion models and the global affine model. PMID- 26539568 TI - Grating coupled SPR microarray analysis of proteins and cells in blood from mice with breast cancer. AB - Biomarker discovery for early disease diagnosis is highly important. Of late, much effort has been made to analyze complex biological fluids in an effort to develop new markers specific for different cancer types. Recent advancements in label-free technologies such as surface plasmon resonance (SPR)-based biosensors have shown promise as a diagnostic tool since there is no need for labeling or separation of cells. Furthermore, SPR can provide rapid, real-time detection of antigens from biological samples since SPR is highly sensitive to changes in surface-associated molecular and cellular interactions. Herein, we report a lab on-a-chip microarray biosensor that utilizes grating-coupled surface plasmon resonance (GCSPR) and grating-coupled surface plasmon coupled fluorescence (GCSPCF) imaging to detect circulating tumor cells (CTCs) from a mouse model (FVB MMTV-PyVT). GCSPR and GCSPCF analysis was accomplished by spotting antibodies to surface cell markers, cytokines and stress proteins on a nanofabricated GCSPR microchip and screening blood samples from FVB control mice or FVB-MMTV-PyVT mice with developing mammary carcinomas. A transgenic MMTV-PyVT mouse derived cancer cell line was also analyzed. The analyses indicated that CD24, CD44, CD326, CD133 and CD49b were expressed in both cell lines and in blood from MMTV-PyVT mice. Furthermore, cytokines such as IL-6, IL-10 and TNF-alpha, along with heat shock proteins HSP60, HSP27, HSc70(HSP73), HSP90 total, HSP70/HSc70, HSP90, HSP70, HSP90 alpha, phosphotyrosine and HSF-1 were overexpressed in MMTV-PyVT mice. PMID- 26539569 TI - Raman technologies in cancer diagnostics. AB - Despite significant effort, cancer still remains a leading cause of death worldwide. In order to reduce its burden, the development and improvement of noninvasive strategies for early detection and diagnosis of cancer are urgently needed. Raman spectroscopy, an optical technique that relies on inelastic light scattering arising from molecular vibrations, is one such strategy, as it can noninvasively probe cancerous markers using only endogenous contrast. In this review, spontaneous, coherent and surface enhanced Raman spectroscopies and imaging, as well as the fundamental principles governing the successful use of these techniques, are discussed. Methods for spectral data analysis are also highlighted. Utilization of the discussed Raman techniques for the detection and diagnosis of cancer in vitro, ex vivo and in vivo is described. The review concludes with a discussion of the future directions of Raman technologies, with particular emphasis on their clinical translation. PMID- 26539570 TI - Halogen mediated voltammetric oxidation of biological thiols and disulfides. AB - The electrochemical generation of the halides, bromine and iodine, in the presence of biologically relevant organosulfur is demonstrated to result in an analytically useful response. In the case of the iodide/iodine redox couple only the thiol causes an increase in the electrochemical oxidative peak current. Conversely, the formed bromine may catalytically oxidise both thiols and disulfides. Hence, the differing reactivities of the halide ions readily allow discrimination between the closely related thiol and disulphide species. For all of the organosulfur species investigated (glutathione, cysteine and homocysteine) micromolar limits of detection are attainable. In the case of the bromine mediated oxidation this sensitivity at least partially arises from the large catalytic amplification, such that, for each disulphide molecule up to ten electrons may be transferred. Ultimately this bromine oxidation results in the formation of the sulfonate species. For the iodine mediated oxidation of the thiols the oxidation proceeds no further than to the formation of the associated disulfide. PMID- 26539571 TI - [Consensus on national criteria for transthoracic echocardiography competence]. AB - Standardised competence assessment in transthoracic echocardiography (TTE) is increasingly demanded. Danish Cardiology Society working group on echocardiography initiated a Delphi study among departments involved in resident TTE training to obtain consensus on national criteria for TTE competence. Consensus was obtained on a list of 21 items relevant for TTE competence assessment. Three items should be performed with great routine after two years and 16 items after five years of training. The working group recommends the list being used for competence assessment of cardiology residents. PMID- 26539572 TI - [Treatment of acute purulent diverticulitis is still not clarified]. AB - Inflammation in colonic diverticula can develop into acute diverticulitis. Treatment varies depending on illness severity. Perforated diverticulitis with faecal peritonitis is treated surgically and Hartmann's procedure is the preferred operation. Peritoneal lavage might be an alternative to resection for purulent peritonitis. However, ongoing randomized trials are awaited to clarify this. PMID- 26539573 TI - [Oxidative stress may cause metastatic disease in patients with colorectal cancer]. AB - Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease. PMID- 26539574 TI - [Postural orthostatic tachycardia syndrome]. AB - Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition of dysautonomia and suspected autoimmunity characterized by abnormal increments in heart rate upon assumption of the upright posture accompanied by symptoms of cerebral hypoperfusion and sympathoexcitation. An increase in heart rate equal to or greater than 30 bpm or to levels higher than 120 bpm during a head-up tilt test is the main diagnostic criterion. Management includes both non pharmacological and pharmacological treatment focusing on stress management, volume expansion and heart rate control. PMID- 26539575 TI - [Danish Cholinesterase Research Unit diagnoses patients with prolonged paralysis after succinylcholine and mivacurium]. AB - The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium. PMID- 26539576 TI - [Aluminium allergy and granulomas induced by vaccinations for children]. AB - Vaccination with aluminium-adsorbed vaccines can induce aluminium allergy with persistent itching subcutaneous nodules at the injection site - vaccination granulomas. In this article we give an overview of childhood aluminium-adsorbed vaccines available in Denmark. Through literature studies we examine the incidence, the symptoms and the prognosis for the vaccination granulomas and the allergy. Finally we discuss the status in Denmark. PMID- 26539577 TI - [More research is needed in telemedicine for well-defined patient groups]. AB - The Whole Systems Demonstrator (WSD), a cluster randomized trial of effects of telehealth, was initiated in 2008 including 3.230 patients from 179 general practices. The objective of this review is to summarize the results from WSD based on publications made so far. Results from five publications show that telehealth reduces mortality (odds ratio 0.54) during 12 months. The use of secondary care is reduced, however, when including costs of telehealth, the total costs are higher for PMID- 26539578 TI - [Alcohol use disorders in elderly people calls for treatment]. AB - The complications related to use of alcohol occur at lower levels of alcohol use in the elderly. Alcohol use disorders (AUD) in the elderly are underestimated and often incorrectly diagnosed. However, evidence indicates that elderly are as likely to benefit from treatment as younger. Screening using Alcohol Use Disorders Identification Test seems to be accurate in identifying AUD among elderly, if the cut-off point is tailored for this age group. The recommended treatment strategy is naltrexone and brief approaches such as motivational interview and supportive consultation in general practice. PMID- 26539579 TI - [Active surveillance is a useful strategy in the management of patients with low risk prostate cancer]. AB - Radical prostatectomy has in randomised settings failed to demonstrate a survival difference in patients with low-risk prostate cancer when tested against an observational strategy. Active surveillance has been introduced in order to reduce overtreatment by distinguishing between cancers with a biological potential, and truly indolent cancers best left untreated. Preliminary results from large prospective active surveillance cohorts are promising; however, uncertainties persist concerning optimal patient selection and follow-up, as well as the long-term safety. PMID- 26539580 TI - Trans-Atlantic Debate: Is an "Endovascular First" Strategy the Optimal Approach for Treating Acute Mesenteric Ischemia? PMID- 26539581 TI - [Not Available]. PMID- 26539582 TI - [In Process Citation]. PMID- 26539583 TI - [Not Available]. PMID- 26539584 TI - [In Process Citation]. PMID- 26539585 TI - [In Process Citation]. PMID- 26539587 TI - [Not Available]. PMID- 26539586 TI - [Paul Brune (1935 - 2015): an dedicated psychiatric survivor and victim of the Nazi regime]. PMID- 26539588 TI - Effects of chloroquine therapy on white blood cells. PMID- 26539589 TI - Circulating reactive plasma cells in the setting of peripheral T-cell lymphoma mimicking plasma cell leukemia. PMID- 26539590 TI - The power of unity. PMID- 26539591 TI - The continuing education challenge. PMID- 26539592 TI - Wildlife disease discoveries. PMID- 26539593 TI - Behind the scenes of higher education reform. PMID- 26539594 TI - Family violence and the family pet. PMID- 26539596 TI - How to introduce and maintain change in the workplace. PMID- 26539595 TI - Mastitis - an udderly complex problem in sheep. PMID- 26539597 TI - SA Citizen Jury. PMID- 26539598 TI - A closer look at veterinary internships in Australia. PMID- 26539599 TI - Vanessa Barrs. PMID- 26539600 TI - [Not Available]. PMID- 26539621 TI - Correction to Reinterpreting the Mechanism of Inhibition of Mycobacterium tuberculosis d-Alanine:d-Alanine Ligase by d-Cycloserine. PMID- 26539622 TI - Use and perception of collars for companion cats in New Zealand. AB - AIMS: To investigate the use and utility of collars for companion cats in New Zealand, and to explore public perception of collar use. METHODS: An online questionnaire was distributed using emails and social media to members of the general public in New Zealand. The questionnaire collected details of respondents, cat ownership status, and responses to a number of questions regarding collar use in cats. RESULTS: A total of 511 responses were collected. Of these, 393/511 (76.9%) reported owning >=1 cat at the time of the survey, and 141/393 (35.9%) stated that >=1 of their cats wore collars and 211/393 (53.7%) had >=1 of their cats micro-chipped. Of the respondents with a pet cat, 351/393 (89.3%) allowed their cats some outdoor access. Respondents mainly used collars for identification and to reduce predation. Reasons for not using collars included cat intolerance of collars, repeated collar loss and concern over collar safety. Differences were found between cat owners and non-owners regarding whether they agreed that cats were important for pest control (43 vs. 25%, p<0.001); that not all cats will tolerate collars (81 vs. 64%, p<0.001); that cats should be kept indoors at night (37 vs. 58%, p<0.001); or disagreed that well fed cats will not catch birds (60 vs. 70%, p=0.04); and disagreed that a cat without a collar was likely to be a stray (85 vs. 76%, p<0.001). Respondents most trusted veterinarians and the Society for the Prevention of Cruelty to Animals as sources of pet care information. CONCLUSIONS: Collar use within this sample of cat owners in New Zealand appeared to be low, with more using microchips for identification. The majority of cat owners in this study indicated their cats had some outdoor access, with collars being used for cat identification and to reduce hunting behaviour. Significant differences existed in opinions on cat management between cat owners and non-owners in this study. It should be noted that this preliminary exploration was based on a self-selected group of respondents and so results and conclusions cannot be extrapolated to the wider population. RELEVANCE: As the most trusted source of information about pet care, an enhanced understanding of cat ownership and management may be of use to veterinarians to promote responsible pet ownership and to develop national policies and practices to improve cat welfare. PMID- 26539620 TI - Next-Generation Testing for Cancer Risk: Perceptions, Experiences, and Needs Among Early Adopters in Community Healthcare Settings. AB - BACKGROUND: Advances in next-generation sequencing (NGS) technologies are driving a shift from single-gene to multigene panel testing for clinical genetic cancer risk assessment (GCRA). This study explored perceptions, experiences, and challenges with NGS testing for GCRA among U.S. community-based clinicians. METHODS: Surveys delivered at initial and 8-month time points, and 12-month tracking of cases presented in a multidisciplinary web-based case conference series, were conducted with GCRA providers who participated in a 235-member nationwide community of practice. RESULTS: The proportion of respondents ordering panel tests rose from 29% at initial survey (27/94) to 44% (46/107) within 8 months. Respondents reported significantly less confidence about interpreting and counseling about NGS compared with single-gene test results (p < 0.0001 for all comparisons). The most cited reasons for not ordering NGS tests included concerns about clinical utility, interpreting and communicating results, and lack of knowledge/skills. Multigene panels were used in 204/668 cases presented during 2013, yielding 37 (18%) deleterious (7% in low/moderate-penetrance genes), 88 (43%) with >=1 variant of uncertain significance, 77 (38%) uninformative negative, and 2 (1%) inconclusive results. CONCLUSIONS: Despite concerns about utility and ability to interpret/counsel about NGS results, a rapidly increasing uptake of NGS testing among community clinicians was documented. Challenges identified in case discussions point to the need for ongoing education, practice based support, and opportunities to partner in research that contributes to characterization of lesser known genes. PMID- 26539626 TI - Resveratrol-Related Polymethoxystilbene Glycosides: Synthesis, Antiproliferative Activity, and Glycosidase Inhibition. AB - A small library of polymethoxystilbene glycosides (20-25) related to the natural polyphenol resveratrol have been synthesized and subjected, together with their aglycones 17-19, to an antiproliferative activity bioassay toward Caco-2 and SH SY5Y cancer cells. Six of the compounds exhibit antiproliferative activity against at least one cell line. In particular, compounds 17 and 18 proved highly active on at least one of the two cell cultures. Compound 18 showed a GI50 value of 3 MUM against Caco-2 cells, a value comparable to that of the anticancer drug 5-fluorouracil. The closely related compound 19 proved inactive, and its conjugates 22 and 25 showed weak cell growth inhibition. The results indicate that minimal differences in the structure of both polymethoxystilbenes and their glycosides can substantially affect the antiproliferative activity. The possible hydrolytic release of the aglycones 17-19 by beta-glucosidase or beta galactosidase was also evaluated. Compounds 20-25 were also tested as potential beta-glucosidase, beta-galactosidase, and alpha-glucosidase inhibitors. A promising inhibitory activity toward alpha-glucosidase was observed for 21 (IC50 = 78 MUM) and 25 (IC50 = 70 MUM), which might be indicative of their potential as lead compounds for development of antidiabetic or antiobesity agents. PMID- 26539625 TI - Ratiometric Organic Fibers for Localized and Reversible Ion Sensing with Micrometer-Scale Spatial Resolution. AB - A fundamental issue in biomedical and environmental sciences is the development of sensitive and robust sensors able to probe the analyte of interest, under physiological and pathological conditions or in environmental samples, and with very high spatial resolution. In this work, novel hybrid organic fibers that can effectively report the analyte concentration within the local microenvironment are reported. The nanostructured and flexible wires are prepared by embedding fluorescent pH sensors based on seminaphtho-rhodafluor-1-dextran conjugate. By adjusting capsule/polymer ratio and spinning conditions, the diameter of the fibers and the alignment of the reporting capsules are both tuned. The hybrid wires display excellent stability, high sensitivity, as well as reversible response, and their operation relies on effective diffusional kinetic coupling of the sensing regions and the embedding polymer matrix. These devices are believed to be a powerful new sensing platform for clinical diagnostics, bioassays and environmental monitoring. PMID- 26539624 TI - Ocular Adverse Events Associated with Antibody-Drug Conjugates in Human Clinical Trials. AB - This article reviews ocular adverse events (AEs) reported in association with administration of antibody-drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (<= grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID- 26539627 TI - Glutamate levels control HT22 murine hippocampal cell death by regulating biphasic patterns of Erk1/2 activation: role of metabolic glutamate receptor 5. AB - Extracellular glutamate concentration is a critical determinant of neuronal cell fate. We recently demonstrated that HT22 murine hippocampal cell viability was reduced by exposure to high concentrations of glutamate, whereas low concentrations promoted cell survival. Extracellular signal-regulated kinase (Erk)1/2 activation by glutamate is important for both glutamate-induced cell death and survival. In this study, we investigated the role of glutamate-induced or hydrogen peroxide (H2O2)-induced Erk1/2 activation in HT22 cell fate determination. Glutamate and H2O2 treatment similarly induced early (<1 h) Erk1/2 phosphorylation regardless of concentration. On the other hand, persistent Erk1/2 phosphorylation (16-24 h) was observed only in the presence of excess glutamate. Only the latter contributed to glutamate-induced cell death, which involved metabolic glutamate receptor 5. Our findings suggest that glutamate concentration modulates two distinct phases of Erk1/2 activation, which can explain the glutamate concentration-dependent determination of HT22 cell fate. PMID- 26539628 TI - Kafirin Nanoparticle-Stabilized Pickering Emulsions as Oral Delivery Vehicles: Physicochemical Stability and in Vitro Digestion Profile. AB - Kafirin nanoparticle-stabilized Pickering emulsions (KPEs) were used to encapsulate curcumin. The stability of KPEs under processing conditions and their protective effects against photo-oxidation of curcumin and lipid oxidation of oil in emulsions, as well as the digestion profiles in gastrointestinal tract, were investigated. KPEs were found to be more stable under acidic than basic environment, and elevated temperature induced their structural instability. The protective effect of KPEs on the chemical stability of curcumin was manifested when subjected to UV radiation as compared to other comparable formulations, such as bulk oil or Tween 80 stabilized emulsions (TEs). Meanwhile, the lipid oxidation rate was retarded in KPEs as compared to those of TEs. Due to hydrolysis of pepsin, KPEs could not survive through the gastric digestion process. After the intestinal digestion process, the extent of lipolysis of KPEs and the curcumin bioaccessibility fell between those of TEs and bulk oil. These results will fill the gap between the physicochemical properties of protein particle-based Pickering emulsions and their realistic applications in the oral delivery of functional food ingredients. PMID- 26539629 TI - Large scale industrialized cell expansion: producing the critical raw material for biofabrication processes. AB - Cellular biomanufacturing technologies are a critical link to the successful application of cell and scaffold based regenerative therapies, organs-on-chip devices, disease models and any products with living cells contained in them. How do we achieve production level quantities of the key ingredient-'the living cells' for all biofabrication processes, including bioprinting and biopatterning? We review key cell expansion based bioreactor operating principles and how 3D culture will play an important role in achieving production quantities of billions to even trillions of anchorage dependent cells. Furthermore, we highlight some of the challenges in the field of cellular biomanufacturing that must be addressed to achieve desired cellular yields while adhering to the key pillars of good manufacturing practices-safety, purity, stability, potency and identity. Biofabrication technologies are uniquely positioned to provide improved 3D culture surfaces for the industrialized production of living cells. PMID- 26539630 TI - Evaluation and optimization of the parameters used in multiple-atlas-based segmentation of prostate cancers in radiation therapy. AB - OBJECTIVE: To evaluate and optimize the parameters used in multiple-atlas-based segmentation of prostate cancers in radiation therapy. METHODS: A retrospective study was conducted, and the accuracy of the multiple-atlas-based segmentation was tested on 30 patients. The effect of library size (LS), number of atlases used for contour averaging and the contour averaging strategy were also studied. The autogenerated contours were compared with the manually drawn contours. Dice similarity coefficient (DSC) and Hausdorff distance were used to evaluate the segmentation agreement. RESULTS: Mixed results were found between simultaneous truth and performance level estimation (STAPLE) and majority vote (MV) strategies. Multiple-atlas approaches were relatively insensitive to LS. A LS of ten was adequate, and further increase in the LS only showed insignificant gain. Multiple atlas performed better than single atlas for most of the time. Using more atlases did not guarantee better performance, with five atlases performing better than ten atlases. With our recommended setting, the median DSC for the bladder, rectum, prostate, seminal vesicle and femurs was 0.90, 0.77, 0.84, 0.56 and 0.95, respectively. CONCLUSION: Our study shows that multiple-atlas-based strategies have better accuracy than single-atlas approach. STAPLE is preferred, and a LS of ten is adequate for prostate cases. Using five atlases for contour averaging is recommended. The contouring accuracy of seminal vesicle still needs improvement, and manual editing is still required for the other structures. ADVANCES IN KNOWLEDGE: This article provides a better understanding of the influence of the parameters used in multiple-atlas-based segmentation of prostate cancers. PMID- 26539632 TI - Experiences of using a commercial dose management system (GE DoseWatch) for CT examinations. AB - OBJECTIVE: To assess the use of a commercial dose management system (GE DoseWatch; GEMS, Milwaukee, WI) for CT dose management for six common CT examinations. METHODS: Data were acquired over several months using GE DoseWatch for six common CT examinations on three CT scanners. The dose length product (DLP) was taken as the dose indicator. The data were analysed using four different filtering methods: study description, the National Interim Clinical Imaging Procedure code, protocol name and a more detailed filtering method (the reference data set). The filtering methods were compared using an analysis of variance and multiple comparison technique. The different scanners were compared using the reference data set. RESULTS: It was found that integrating DoseWatch with the radiology information system provided improved results compared with using the study description. Filtering by study description was found to be a poor indicator of the mean dose for all three scanners and consistently overestimated (p < 0.05) the head and thorax-abdo-pelvis mean DLP values, despite the large sample sizes. Filtering by the National Interim Clinical Imaging Procedure code or protocol name produced mean DLPs which were not statistically different from the reference data. The scanner intercomparison showed some significant differences between the scanners, usually due to different tube current modulation settings. CONCLUSION: The use of a commercial dose monitoring system provided fast and efficient filtering of substantial amounts of data. The filtering method affected the mean DLP value despite large sample sizes. ADVANCES IN KNOWLEDGE: Dose management systems are relatively new in the UK, and this article shares knowledge on the use of one system. PMID- 26539631 TI - The curative management of synchronous rectal and prostate cancer. AB - OBJECTIVE: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. METHODS: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. RESULTS: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5 fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. CONCLUSION: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients. PMID- 26539633 TI - Focal pleural thickening mimicking pleural plaques on chest computed tomography: tips and tricks. AB - Diagnosis of pleural plaques (PPs) is commonly straightforward, especially when a typical appearance is observed in a context of previous asbestos exposure. Nevertheless, numerous causes of focal pleural thickening may be seen in routine practice. They may be related to normal structures, functional pleural thickening, previous tuberculosis, pleural metastasis, silicosis or other rarer conditions. An application of a rigorous technical approach as well as a familiarity with loco-regional anatomy and the knowledge of typical aspects of PP are required. Indeed, false-positive or false-negative results may engender psychological and medico-legal consequences or can delay diagnosis of malignant pleural involvement. Correct recognition of PPs is crucial, as they may also be an independent risk factor for mortality from lung cancer in asbestos-exposed workers particularly in either smokers or former/ex-smokers. Finally, the presence of PP(s) may help in considering asbestosis as a cause of interstitial lung disease predominating in the subpleural area of the lower lobes. The aim of this pictorial essay is to provide a brief reminder of the normal anatomy of the pleura and its surroundings as well as the various aspects of PPs. Afterwards, the common pitfalls encountered in PP diagnosis will be emphasized and practical clues to differentiate actual plaque and pseudoplaque will be concisely described. PMID- 26539634 TI - Therapeutic Applications of Aptamer-Based Riboswitches. AB - Aptamers bind to their targets with high affinity and specificity through structure-based complementarity, instead of sequence complementarity that is used by most of the oligonucleotide-based therapeutics. This property has been exploited in using aptamers as multifunctional therapeutic units, by attaching them to therapeutic drugs, nanoparticles, or imaging agents, or as direct molecular decoys for inducing loss-of-function or gain-of-function of targets. One of the most interesting fields of aptamer application is their development as molecular sensors to regulate artificial riboswitches. Naturally, the riboswitches sense small-molecule metabolites and respond by regulating the expression of the corresponding metabolic genes. Riboswitches are cis-acting RNA structures that consist of the sensing (aptamer) and the regulating (expression platform) domains. In principle, diverse riboswitches can be engineered and applied to control different steps of gene expression in bacterial species as well as eukaryotes, by simply replacing aptamers against various endogenous and/or exogenous targets. Although these engineered aptamer-based riboswitches are recently gaining attention, it is clear that aptamer-based riboswitches have a potential for next-generation therapeutics against various diseases because of their controllability, specificity, and modularity in regulating gene expression through various cellular processes, including transcription, splicing, stability, RNA interference, and translation. In this review, we provide a summary of the recently developed and engineered aptamer-based riboswitches focusing on their therapeutic availability and further discuss their clinical potential. PMID- 26539635 TI - Outcome of Cervical Radiculopathy Treated with Periradicular/Epidural Corticosteroid Injections. PMID- 26539636 TI - Notice to Readers. PMID- 26539638 TI - Polydimethylsiloxane bilayer films with an embedded spontaneous curvature. AB - Elastomer polydimethylsiloxane (PDMS) films with embedded in-plane gradient stress are created by making PDMS/(PDMS + silicone oil) crosslinked bilayers and extracting the oil in a suitable organic solvent bath. The collapse of the elastomer after oil extraction generates differential stress in the films that is manifested through their out-of-plane deformation. The curvature kappa of narrow stripes of the bilayer, which is composed of layers of approximately equal thicknesses and elasticity moduli, is satisfactorily described by the simple relationship kappa = 1.5deltaH(-1), where delta is the mechanical strain, and H is the total thickness of the bilayer. Curvature mapping of triangular PDMS plates reveals the existence of spherical and cylindrical types of deformation at different locations of the plates. Various 3D-shaped objects can be formed by the self-folding of appropriately designed 2D patterns that are cut from the films, or by nonuniform distribution of the collapsing layer. Thin PDMS bilayers with embedded stress roll up into microtubes of almost perfect cylindrical shape when released in a controlled manner from a substrate. PMID- 26539639 TI - Engineering Systems with Spatially Separated Enzymes via Dual-Stimuli-Sensitive Properties of Microgels. AB - This work examines the adsorption regime and the properties of microgel/enzyme thin films deposited onto conductive graphite-based substrates. The films were formed via two-step sequential adsorption. A temperature- and pH-sensitive poly(N isopropylacrylamide)-co-(3-(N,N-dimethylamino)propylmethacrylamide) microgel (poly(NIPAM-co-DMAPMA microgel) was adsorbed first, followed by its interaction with the enzymes, choline oxidase (ChO), butyrylcholinesterase (BChE), or mixtures thereof. By temperature-induced stimulating both (i) poly(NIPAM-co DMAPMA) microgel adsorption at T > VPTT followed by short washing and drying and then (ii) enzyme loading at T < VPTT, we can effectively control the amount of the microgel adsorbed on a hydrophobic interface as well as the amount and the spatial localization of the enzyme interacted with the microgel film. Depending on the biomolecule size, enzyme molecules can (in the case for ChO) or cannot (in the case for BChE) penetrate into the microgel interior and be localized inside/outside the microgel particles. Different spatial localization, however, does not affect the specific enzymatic responses of ChO or BChE and does not prevent cascade enzymatic reaction involving both BChE and ChO as well. This was shown by the methods of electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), and amperometric analysis of enzymatic responses of immobilized enzymes. Thus, a novel simple and fast strategy for physical entrapment of biomolecules by the polymeric matrix was proposed, which can be used for engineering systems with spatially separated enzymes of different types. PMID- 26539640 TI - Disease-Specific Hashtags for Online Communication About Cancer Care. PMID- 26539641 TI - Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia. AB - Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems. PMID- 26539642 TI - Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans. AB - Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of 'core' direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway. PMID- 26539643 TI - The role of N-glycans in colorectal cancer progression: potential biomarkers and therapeutic applications. AB - Changes in glycosylation, which is one of the most common protein post translational modifications, are considered to be a hallmark of cancer. N-glycans can modulate cell migration, cell-cell adhesion, cell signaling, growth and metastasis. The colorectal cancer (CRC) is a leading cause of cancer-related mortality and the correlation between CRC progression and changes in the pattern of expression of N-glycans is being considered in the search for new biomarkers. Here, we review the role of N-glycans in CRC cell biology. The perspectives on emerging N-glycan-related anticancer therapies, along with new insights and challenges, are also discussed. PMID- 26539644 TI - Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response. AB - Attenuated measles virus (MV) is currently being evaluated as an oncolytic virus in clinical trials and could represent a new therapeutic approach for malignant pleural mesothelioma (MPM). Herein, we screened the sensitivity to MV infection and replication of twenty-two human MPM cell lines and some healthy primary cells. We show that MV replicates in fifteen of the twenty-two MPM cell lines. Despite overexpression of CD46 by a majority of MPM cell lines compared to healthy cells, we found that the sensitivity to MV replication did not correlate with this overexpression. We then evaluated the antiviral type I interferon (IFN) responses of MPM cell lines and healthy cells. We found that healthy cells and the seven insensitive MPM cell lines developed a type I IFN response in presence of the virus, thereby inhibiting replication. In contrast, eleven of the fifteen sensitive MPM cell lines were unable to develop a complete type I IFN response in presence of MV. Finally, we show that addition of type I IFN onto MV sensitive tumor cell lines inhibits replication. These results demonstrate that defects in type I IFN response are frequent in MPM and that MV takes advantage of these defects to exert oncolytic activity. PMID- 26539645 TI - Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis. AB - Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy. PMID- 26539646 TI - PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia. AB - In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors.We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 - 190052 pmol PAR/106 cells) compared to that seen in healthy volunteer lymphocytes (2451 - 7519 pmol PAR/106 cells). PARP activity was associated with PARP1 protein expression and endogenous PAR levels. PARP activity was not associated with p53 or ATM loss, Binet stage, IGHV mutational status or survival, but correlated with Bcl-2 and Rel A (an NF-kB subunit). Levels of 8-hydroxy-2' deoxyguanosine in DNA (a marker of oxidative damage) were not associated with PAR levels or PARP activity. The potent PARP inhibitor, talazoparib (BMN 673), inhibited CD40L-stimulated proliferation of CLL cells at nM concentrations, independently of Binet stage or p53/ATM function.PARP activity is highly variable in CLL and correlates with stress-induced proteins. Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib. PMID- 26539647 TI - C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients. AB - BACKGROUND: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5-10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. METHODS: A total of 63 chronic HD patients (6.0 +/- 17 years, M/F:44/19) and 20 healthy controls (6.0 +/- 4 years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. RESULTS: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r = 0.55, p < 0.001). In HD patients, serum hepcidin levels were associated with ferritin (r = 0.55, p < 0.01) and creatinine (r = 0.27, p = 0.03). Dose of ESA was significantly associated with serum CRP (r = 0.34, p = 0.02), total protein (r = -0.34, p = 0.01), transferrin (r = -0.28, p = 0.04) and ferritin (r = 0.31, p = 0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R = 0.62, R(2) =0 .38, p = 0.02). Serum CRP was the only significant factor predicting ERI. CONCLUSION: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance. PMID- 26539648 TI - Effects of two calcium silicate cements on cell viability, angiogenic growth factor release and related gene expression in stem cells from the apical papilla. AB - AIM: To evaluate the effects of two types of calcium silicate cements on viability, angiogenic growth factor release, and angiogenic and inflammation related gene expression in human stem cells from the apical papilla (SCAP). METHODOLOGY: SCAPs were grown for 7 days with either ProRoot mineral trioxide aggregate (MTA) or Biodentine (BD). Cell viability and media concentrations of vascular endothelial growth factor (VEGF/VEGFA) and angiopoietin 1 (ANGPT1) were measured. The expression of genes related to angiogenic potential and inflammatory response was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). One-way and two-way analyses of variance with multiple comparisons Tukey's test were performed (P < 0.05). RESULTS: Cells in contact with either cement were associated with increased cell viability compared with the no-treatment group at day 1 but there were no differences amongst groups at days 3 and 7. Exposure to either cement significantly increased VEGF concentrations at day 3; however, ANGPT-1 levels decreased significantly compared with the no-treatment group at day 3. Exposure to MTA and BD stimulated expression of VEGFA and FIGF/VEGFD. Furthermore, exposure to both cements significantly decreased the mRNA levels of ANGPT1 and FGF2 relative to the no treatment group. CONCLUSIONS: Both MTA and BD stimulated the expression of angiogenic genes and release of VEGF, inducing similar expression patterns; however, they appeared to inhibit the expression of specific genes, including ANGPT1 and FGF2. PMID- 26539651 TI - Generalizable Synthesis of Metal-Sulfides/Carbon Hybrids with Multiscale, Hierarchically Ordered Structures as Advanced Electrodes for Lithium Storage. AB - Transition-metal sulfides/carbon hybrids with a multiscale, multidimensional, and hierarchically ordered architecture have been designed and synthesized by a general and facile method. As a result of this novel and unique architecture design, the obtained hybrid electrodes show attractive reversibility and cycle stability as well as excellent rate capability. PMID- 26539650 TI - A Comparison of Statin Therapies in Hypercholesterolemia in Women: A Subgroup Analysis of the STELLAR Study. AB - OBJECTIVE: Cardiovascular disease is the leading cause of mortality in women in the United States. Aggressive treatment of modifiable risk factors (e.g., hypercholesterolemia) is essential in reducing disease burden. Despite guidelines recommending the use of statin treatment in hypercholesterolemic women, this patient group is often undertreated. This subgroup analysis of the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial examines the effects of statin therapy in hypercholesterolemic women. METHODS: As part of the STELLAR trial, 1,146 women with elevated low density lipoprotein cholesterol (LDL-C >=160 and <250 mg/dL) and triglycerides <400 mg/dL were randomized to rosuvastatin 10-40 mg, atorvastatin 10-80 mg, simvastatin 10-80 mg, or pravastatin 10-40 mg for 6 weeks. RESULTS: LDL-C reduction with rosuvastatin 10 mg, atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg was 49%, 39%, 37%, and 30%, respectively, after 6 weeks. High intensity statins (rosuvastatin 20-40 mg and atorvastatin 40-80 mg) reduced LDL-C to the greatest extent: 53% with rosuvastatin 20 mg, 57% with rosuvastatin 40 mg, 47% with atorvastatin 40 mg, and 51% with atorvastatin 80 mg. Similar results were observed for non-high-density lipoprotein cholesterol (non-HDL-C). Increases in HDL-C were greater with rosuvastatin across doses than with other statins. All treatments were well tolerated, with similar safety profiles across dose ranges. CONCLUSIONS: Statin therapies in the STELLAR trial led to reductions in LDL-C, non-HDL-C, and triglycerides and increases in HDL-C among hypercholesterolemic women, with rosuvastatin providing the greatest reductions in LDL-C and non-HDL C. PMID- 26539652 TI - Effect of particle size on magnetic and electric transport properties of La(0.67)Sr(0.33)MnO3 coatings. AB - A systematic study of polycrystalline La0.67Sr0.33MnO3 (LSMO) manganite coatings has been undertaken to analyse the effect of various particle sizes on the magnetic and electric transport properties. In order to acquire a series of samples with different particle sizes, the samples were prepared by a sol-gel method and were subjected to annealing at four different temperatures. With decreasing particle sizes, the magnetization decreases while the coercivity increases, which is attributed to the magnetically disordered surface layer. More attractively, the electrical transport properties can be systematically manipulated by particle sizes and so can the low field magnetoresistance (LFMR) values. Emphasis is placed on how the particle size affects the temperature dependence of resistivity, and three conduction models are explored to describe the transport behaviours in three temperature regions. A minimum resistivity is observed in the low temperature region in the presence and absence of a magnetic field, which can be mainly explained as due to the intergranular spin polarized tunneling (ISPT) through the grain boundaries (GBs) in polycrystalline materials. PMID- 26539653 TI - Access to the Surugatoxin Alkaloids: Chemo-, Regio-, and Stereoselective Oxindole Annulation. AB - We report the synthesis of an aglycone of the surugatoxin family. The synthesis of this surugatoxin core was accomplished in 13 steps using a new oxindole annulation and late-stage enamine oxidation. PMID- 26539654 TI - Triple-Stimuli-Responsive Ferrocene-Containing PEGs in Water and on the Surface. AB - Triple-stimuli-responsive PEG-based materials are prepared by living anionic ring opening copolymerization of ethylene oxide and vinyl ferrocenyl glycidyl ether and subsequent thiol-ene postpolymerization modification with cysteamine. The hydrophilicity of these materials can be tuned by three stimuli: (i) temperature (depending on the comonomer ratio), (ii) oxidation state of iron centers in the ferrocene moieties, and (iii) pH-value (through amino groups), both in aqueous solution and at the interface after covalent attachment to a glass surface. In such materials, the cloud point temperatures are adjustable in solution by changing oxidation state and/or pH. On the surface, the contact angle increases with increasing pH and temperature and after oxidation, making these smart surfaces interesting for catalytic applications. Also, their redox response can be switched by temperature and pH, making this material useful for catalysis and electrochemistry applications. Exemplarily, the temperature-dependent catalysis of the chemiluminescence of luminol (a typical blood analysis tool in forensics) was investigated with these polymers. PMID- 26539655 TI - Who wants to go to occupational therapy school? Characteristics of Norwegian occupational therapy students. AB - BACKGROUND: Research on occupational therapy students has often been concerned with quite narrow topics. However, the basic characteristics of this group are yet to be examined in more depth. METHODS: This study aimed to explore the sociodemographic, education-related, and work-related characteristics of occupational therapy students. A sample of 160 occupational therapy students in Norway participated. Differences between cohorts of students were examined with one-way analyses of variance (ANOVA) for continuous variables and with chi-square tests for categorical variables. RESULTS: The sample had a mean age of 24 years and was predominantly female (79%). More than one -third of the students had one or both parents in an occupation requiring health education, whereas two-thirds of the students had one or both parents in an occupation requiring higher education. At entry, 57% of the participants had occupational therapy as their preferred choice of education and 43% had previous higher education experience. The few significant differences between the study cohorts were negligible. CONCLUSION: In the education programmes, specific attention may be considered for students with characteristics associated with increased risk of poorer study performance or other problems. This may concern male students and students with no previous higher education experience. PMID- 26539656 TI - The complete mitochondrial genome and phylogenetic position of the Philippines spurdog, Squalus montalbani. AB - We present the complete mitochondrial genome sequence (16 555 bp) of the Philippines spurdog, Squalus montalbani, currently listed as Vulnerable due to population declines and fishing pressures. A phylogenetic analysis was carried out on S. montalbani and representative shark mitogenomes. Squalus montalbani was placed within the Squaliformes as a sister taxon to Squalus acanthias and Cirrhigaleus australis. PMID- 26539657 TI - Older Adult Perceptions of Participation in Group- and Home-Based Falls Prevention Exercise. AB - This paper describes why older adults begin, continue, and discontinue group- and home-based falls prevention exercise and benefits and barriers to participation. Telephone surveys were used to collect data for 394 respondents. Most respondents reported not participating in group- (66%) or home-based (78%) falls prevention exercise recently. Reasons for starting group-based falls prevention exercise include health benefits (23-39%), health professional recommendation (13-19%), and social interaction (4-16%). They discontinued because the program finished (44%) or due to poor health (20%). Commonly reported benefits were social interaction (41-67%) and health (15-31%). Disliking groups was the main barrier (2-14%). Home-based falls prevention exercise was started for rehabilitation (46 63%) or upon health professional recommendation (22-48%) and stopped due to recovery (30%). Improvement in health (18-46%) was the main benefit. These findings could assist health professionals in prescribing group-based falls prevention exercise by considering characteristics of older adults who perceive social interaction to be beneficial. PMID- 26539658 TI - Advances in template-based protein docking by utilizing interfaces towards completing structural interactome. AB - The increase in the number of structurally determined protein complexes strengthens template-based docking (TBD) methods for modelling protein-protein interactions (PPIs). These methods utilize the known structures of protein complexes as templates to predict the quaternary structure of the target proteins. The templates may be partial or complete structures. Interface based (partial) methods have recently gained interest due in part to the observation that the interface regions are reusable. We describe how available template interfaces can be used to obtain the structural models of protein interactions. Despite the agreement that a majority of the protein complexes can be modelled using the available Protein Data Bank (PDB) structures, a handful of studies argue that we need more template proteins to increase the structural coverage of PPIs. We also discuss the performance of the interface TBD methods at large scale, and the significance of capturing multiple conformations for improving accuracy. PMID- 26539659 TI - Depression, Anxiety, and Regret Before and After Testing to Estimate Uveal Melanoma Prognosis. AB - IMPORTANCE: To our knowledge, longitudinal assessment of depression, anxiety, and decision regret (a sense of disappointment or dissatisfaction in the decision) in patients undergoing prognostication for uveal melanoma does not exist. OBJECTIVE: To report on depression, anxiety, and decision regret before and after testing to estimate uveal melanoma prognosis. DESIGN, SETTING, AND PARTICIPANTS: Prospective interventional case series conducted at an institutional referral practice of 96 patients with clinical diagnosis of uveal melanoma who underwent prognostication at the time of primary therapy. MAIN OUTCOMES AND MEASURES: Depression, anxiety, and decision regret prior to prognostication (baseline) and at 3 and 12 months afterwards. The Hospital Anxiety and Depression Scale (HADS) and Decision Regret Scale were self-administered by the patients prior to prognostication (baseline) and at 3 and 12 months afterwards. Data were summarized using means and standard deviations for continuous measures, frequencies, and percentages for categorical factors. A mixed model was used to assess the trajectory of HADS anxiety and the associations between HADS anxiety and baseline HADS depression, baseline decision regret, prognostication test result, and adjuvant therapy, respectively, while adjusting for age and sex. RESULTS: Ninety-six patients (median age 60.7 years) completed baseline questionnaires. The mean (SD) HADS anxiety score at baseline (7.4 [4.0]) was higher than at 3 months (5.4 [3.7]; P < .001) or 12 months (4.7 [3.4]; P < .001), and decreased with older age (coefficient estimate [SD], -0.06 [0.02]; P < .001). The decision regret score was associated with baseline HADS depression score (coefficient estimate [SE], -1.17 [0.43]; P < .007), and HADS depression score increased with baseline HADS anxiety score (coefficient estimate [SE], 0.39 [0.06]; P < .001). CONCLUSIONS AND RELEVANCE: Our study raises questions about decision regret in patients who agree to have a prognostic test that may not help guide treatment. Although decision regret appears to lessen or dissipate with time, study on larger numbers of patients is necessary to elucidate factors that may be addressed to mitigate decision regret. PMID- 26539660 TI - Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release. AB - Poly(ethylene glycol) (PEG) hydrogels are widely used to deliver therapeutic biomolecules, due to high hydrophilicity, tunable physicochemical properties, and anti-fouling properties. Although different hydrogel crosslinking mechanisms are known to result in distinct network structures, it is still unknown how these various mechanisms influence biomolecule release. Here we compared the effects of chain-growth and step-growth polymerization for hydrogel crosslinking on the efficiency of protein release and diffusivity. For chain-growth-polymerized PEG hydrogels, while decreasing PEG concentration increased both the protein release efficiency and diffusivity, it was unexpected to find out that increasing PEG molecular weight did not significantly change either parameter. In contrast, for step-growth-polymerized PEG hydrogels, both decreasing PEG concentration and increasing PEG molecular weight resulted in an increase in the protein release efficiency and diffusivity. For step-growth-polymerized hydrogels, the protein release efficiency and diffusivity were further decreased by increasing crosslink functionality (4-arm to 8-arm) of the chosen monomer. Altogether, our results demonstrate that the crosslinking mechanism has a differential effect on controlling protein release, and this study provides valuable information for the rational design of hydrogels for sophisticated drug delivery. PMID- 26539661 TI - Maternal high-fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring. AB - BACKGROUND: We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. METHODS: On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. RESULTS: Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection. CONCLUSION: Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition. PMID- 26539662 TI - Fast Doppler as a novel bedside measure of cerebral perfusion in preterm infants. AB - BACKGROUND: Altered cerebral perfusion from impaired autoregulation may contribute to the morbidity and mortality associated with premature birth. We hypothesized that fast Doppler imaging could provide a reproducible bedside estimation of cerebral perfusion and autoregulation in preterm infants. METHODS: This is a prospective pilot study using fast Doppler ultrasound to assess blood flow velocity in the basal ganglia of 19 subjects born at 26-32 wk gestation. Intraclass correlation provided a measure of test-retest reliability, and linear regression of cerebral blood flow velocity and heart rate or blood pressure allowed for estimations of autoregulatory ability. RESULTS: The intraclass correlation when imaging in the first 48 h of life was 0.634. We found significant and independent correlations between the systolic blood flow velocity and both systolic blood pressure and heart rate (P = 0.015 and 0.012 respectively) only in the 26-28 wk gestational age infants in the first 48 h of life. CONCLUSION: Our results suggest that fast Doppler provides reliable bedside measurements of cerebral blood flow velocity at the tissue level in premature infants, acting as a proxy for cerebral tissue perfusion. Additionally, autoregulation appears to be impaired in the extremely preterm infants, even within a normal range of blood pressures. PMID- 26539664 TI - Cross-sectional and longitudinal growth patterns in osteogenesis imperfecta: implications for clinical care. AB - BACKGROUND: There is strikingly limited information on linear growth and weight in the different types of osteogenesis imperfecta (OI). Here, we define growth patterns further with the intent of implementing appropriate adaptations proactively. METHODS: We report cross-sectional anthropometric data for 343 subjects with different OI types (144 children, 199 adults). Longitudinal height data for 36 children (18 girls, 18 boys) with OI type I and 10 children (8 girls, 2 boys) with OI type III were obtained. RESULTS: In all cases, the height Z scores were negatively impacted, and final height Z-scores were impacted the most. In type I, the growth velocities taper near puberty, and there is a blunted pubertal growth spurt. The growth velocities of children with type III decelerate before age 5 y; poor growth continues without an obvious pubertal growth spurt. Obesity is a concern for all patients with OI, with type III patients being the most affected. CONCLUSION: The linear growth patterns, in addition to the marked increase in weight over time, indicate a need for lifestyle modifications early in childhood, especially a need for weight control. Further definition of the anthropometric measures in OI enables patients to begin modifications as early as possible. PMID- 26539663 TI - Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis. AB - BACKGROUND: Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. METHODS: Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. RESULTS: Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. CONCLUSION: Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID- 26539665 TI - Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model. AB - BACKGROUND: Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway. METHODS: Pregnant C57/Bl6 dams were injected with lipopolysaccharide (LPS) or saline on embryonic day 16. Offspring were placed in room air or hyperoxia (50% O2) for 7 d and then returned to normoxia. Airway mechanics, histology, and laser capture micro-dissection (LCM) were performed. RESULTS: At postnatal day 21, maternal LPS- and 50% O2-exposed pups exhibited increased resistance and decreased compliance compared to 21% O2 pups; however their effects were not synergistic. LPS and hyperoxia each increased the thickness of airway smooth muscle (ASM), but not the airway epithelial layer. Structural changes were largely limited to the conducting airways. Upregulation of inflammatory markers in the lung was observed at birth. LCM revealed increased collagen-3, transforming growth factor beta, and connective tissue growth factor expression with LPS and hyperoxia within the ASM layer. CONCLUSION: These novel studies provide functional, structural, and molecular evidence that antenatal inflammation is detrimental to the developing airway. Exposure to moderate hyperoxia does not exacerbate LPS effects on the airway. PMID- 26539666 TI - New developments in cerebral blood flow autoregulation analysis in preterm infants: a mechanistic approach. AB - BACKGROUND: Impaired autoregulation capacity implies that changes in cerebral perfusion follow changes in blood pressure; however, no analytical method has explored such a signal causality relationship in infants. We sought to develop a method to assess cerebral autoregulation from a mechanistic point of view and explored the predictive capacity of the method to classify infants at risk for adverse outcomes. METHODS: The partial directed coherence (PDC) method, which considers synchronicity and directionality of signal dependence across frequencies, was used to analyze the relationship between spontaneous changes in mean arterial pressure (MAP) and the cerebral tissue oxygenation index (TOI). PDCMAP>>TOI indicated that changes in TOI were induced by MAP changes, and PDCTOI>>MAP indicated the opposite. RESULTS: The PDCMAP>>TOI and PDCTOI>>MAP values differed. PDCMAP>>TOI adjusted by gestational age predicted low superior vena cava flow (<=41 ml/kg per min), with an area under the receiver operating characteristic curve of 0.72 (95% CI: 0.63-0.81; P < 0.001), whereas PDCTOI>>MAP did not. The adjusted pPDCMAP>>TOI (the average value per patient) predicted severe intracranial hemorrhage and mortality. CONCLUSION: PDCMAP>>TOI allows for a noninvasive physiological interpretation of the pressure autoregulation process in neonates. PDCMAP>>TOI is a good classifier for infants at risk of brain hypoperfusion and adverse outcomes. PMID- 26539668 TI - The Role of Surface Passivation in Controlling Ge Nanowire Faceting. AB - In situ transmission electron microscopy observations of nanowire morphologies indicate that during Au-catalyzed Ge nanowire growth, Ge facets can rapidly form along the nanowire sidewalls when the source gas (here, digermane) flux is decreased or the temperature is increased. This sidewall faceting is accompanied by continuous catalyst loss as Au diffuses from the droplet to the wire surface. We suggest that high digermane flux and low temperatures promote effective surface passivation of Ge nanowires with H or other digermane fragments inhibiting diffusion and attachment of Au and Ge on the sidewalls. These results illustrate the essential roles of the precursor gas and substrate temperature in maintaining nanowire sidewall passivation, necessary to ensure the growth of straight, untapered, ?111?-oriented nanowires. PMID- 26539667 TI - Umbilical cord gene expression reveals the molecular architecture of the fetal inflammatory response in extremely preterm newborns. AB - BACKGROUND: The fetal inflammatory response (FIR) in placental membranes to an intrauterine infection often precedes premature birth raising neonatal mortality and morbidity. However, the precise molecular events behind FIR still remain largely unknown, and little has been investigated at gene expression level. METHODS: We collected publicly available microarray expression data profiling umbilical cord (UC) tissue derived from the cohort of extremely low gestational age newborns (ELGANs) and interrogate them for differentially expressed (DE) genes between FIR and non-FIR-affected ELGANs. RESULTS: We found a broad and complex FIR UC gene expression signature, changing up to 19% (3,896/20,155) of all human genes at 1% false discovery rate. Significant changes of a minimum 50% magnitude (1,097/3,896) affect the upregulation of many inflammatory pathways and molecules, such as cytokines, toll-like receptors, and calgranulins. Remarkably, they also include the downregulation of neurodevelopmental pathways and genes, such as Fragile-X mental retardation 1 (FMR1), contactin 1 (CNTN1), and adenomatous polyposis coli (APC). CONCLUSION: The FIR expression signature in UC tissue contains molecular clues about signaling pathways that trigger FIR, and it is consistent with an acute inflammatory response by fetal innate and adaptive immune systems, which participate in the pathogenesis of neonatal brain damage. PMID- 26539669 TI - Spatiotemporal dynamics of solvent-assisted lipid bilayer formation. AB - The solvent-assisted lipid bilayer (SALB) method offers a general strategy to fabricate supported lipid bilayers on solid surfaces. In this method, lipids dissolved in alcohol are deposited on the target substrate in parallel with their aggregation during exchange with aqueous buffer solution which promotes spontaneous bilayer formation. Herein, a combination of experimental and theoretical approaches is employed in order to understand the key aspects of the SALB formation process. Epifluorescence microscopy experiments are conducted in order to measure the spatiotemporal dynamics of bilayer formation on a glass substrate in a microfluidic channel. Corresponding snapshots of bilayer formation at different stages are rationalized by a numerical simulation of solvent displacement inside the channel. Comparing simulation with experiment indicates that in close proximity to the side walls of the present setup, the bilayer formation is confined to a relatively thin region behind the moving solvent displacement front. PMID- 26539670 TI - Comparison of two surgeries in treatment of severe kyphotic deformity caused by ankylosing spondylitis: Transpedicular bivertebrae wedge osteotomy versus one stage interrupted two-level transpedicular wedge osteotomy. AB - OBJECTIVE: To explore a simple and effective surgery for correcting severe kyphotic deformity caused by ankylosing spondylitis (AS). MATERIALS AND METHODS: From January 2003 to December 2009, we respectively reviewed 32 patients with severe spinal kyphosis caused by AS with at least 2-year follow-up. Patients were divided into two groups, according to surgical methods: transpedicular bivertebrae wedge osteotomy (Group A) or one-stage interrupted two-level transpedicular wedge osteotomy (Group B). We recorded operating time and blood loss. Variation between pre- and post-operative sagittal imbalance, global spinal alignments (Cobb angle of T1 and L5, TLKA), lumbar lordosis, chin-brow vertical angle, thoracolumbar kyphosis angle in both groups were analyzed. RESULTS: The average operating time was 236 +/- 39 min and the average blood loss was 2200 +/- 712 ml in Group A, and 252 +/- 43 min, 2202 +/- 737 ml respectively in Group B. There were no significant differences in operating time and blood loss. Variation between pre- and post-operative sagittal imbalance, global spinal alignments, lumbar lordosis and chin-brow vertical angle (CBVA) were comparable between the two groups. The variation of thoracolumbar kyphosis angle was significantly greater in Group B compared with Group A. SRS-22 scores were similar in the two groups at the 2-year follow-up and significantly improved compared with preoperative. CONCLUSIONS: For correcting severe kyphosis in patients with AS, the one-stage interrupted two-level transpedicular wedge osteotomy is a safe and effective technique which can significantly improve the thoracolumbar kyphosis angle. PMID- 26539672 TI - Imaging demonstration of trochlear nerve agenesis in superior oblique palsy emerging during the later life. AB - BACKGROUND: Congenital trochlear palsy may manifest with sudden vertical diplopia due to decompensation during the later life, which may bring a diagnostic challenge. CASE PRESENTATION: Two men with vertical diplopia for several years after age of 50 were referred with persisting or suddenly aggravating diplopia. Findings were consistent with unilateral superior oblique palsy (SOP) in both patients with a contraversive head tilt. Facial asymmetry was suggestive of a congenital cause in a patient. High resolution magnetic resonance image (MRI)s disclosed atrophic superior oblique and absent trochlear nerve in the side of SOP in both patients. CONCLUSION: Imaging demonstration of superior oblique atrophy and absent trochlear nerve may aid in diagnosis of congenital SOP presenting sudden vertical diplopia during the later life due to delayed decompensation. PMID- 26539671 TI - Pennsylvania comprehensive stroke center collaborative: Statement on the recently updated IV rt-PA prescriber information for acute ischemic stroke. AB - OBJECTIVE: Recently, the FDA guidelines regarding the eligibility of patients with acute ischemic stroke to receive IV rt-PA have been modified and are not in complete accord with the latest AHA/ASA guidelines. The resultant differences may result in discrepancies in patient selection for intravenous thrombolysis. METHODS: Several comprehensive stroke centers in the state of Pennsylvania have undertaken a collaborative effort to clarify and unify our own recommendations regarding how to reconcile these different guidelines. RESULTS: Seizure at onset of stroke, small previous strokes that are subacute or chronic, multilobar infarct involving more than one third of the middle cerebral artery territory on CT scan, hypoglycemia, minor or rapidly improving symptoms should not be considered as contraindications for intravenous thrombolysis. It is recommended to follow the AHA/ASA guidelines regarding blood pressure management and bleeding diathesis. Patients receiving factor Xa inhibitors and direct thrombin inhibitors within the preceding 48 h should be excluded from receiving IV rt-PA. CT angiography is effective in identifying candidates for endovascular therapy. Consultation with and/or transfer to a comprehensive stroke center should be an option where indicated. Patients should receive IV rt-PA up to 4.5h after the onset of stroke. CONCLUSIONS: The process of identifying patients who will benefit the most from IV rt-PA is still evolving. Considering the rapidity with which patients need to be evaluated and treated, it remains imperative that systems of care adopt protocols to quickly gather the necessary data and have access to expert consultation as necessary to facilitate best practices. PMID- 26539673 TI - Evolution of a Revolution in Occupational Therapy Education. AB - This issue of the American Journal of Occupational Therapy reflects an increase in the quantity and quality of scholarly projects submitted for publication in this special issue. The positive response to the call for papers is evidence of the focused interest that faculty, both academic and clinical, and practitioners have brought to their work of educating and preparing the next generation of occupational therapists. This article discusses educational issues from academic, student, and fieldwork points of view, further validating the pervasive commitment that is being made to further understanding of how occupational therapists are educated. The articles cover topics including the critical issues of curriculum, value and timing of fieldwork and simulation experiences, and documentation of strategies to measure the effects of comparative educational experiences. PMID- 26539674 TI - Impact of a Curricular Change on Perceived Knowledge, Skills, and Use of Evidence in Occupational Therapy Practice: A Cohort Study. AB - OBJECTIVE: We evaluated the impact of a curriculum revision that emphasized experiential use of evidence in clinical environments on occupational therapy graduates' attitudes, perceived knowledge and skill, and use of evidence in practice. METHODS: We used a retrospective cohort design to compare two curriculum cohorts of recent graduates exposed to different evidence-based practice (EBP) educational approaches. Responses on a validated survey of attitudes, knowledge/skill, and use of evidence in practice were compared using t tests and Mann-Whitney U tests for Cohort 1 (n = 63) and Cohort 2 (n = 62) graduates. RESULTS: Findings suggest similar attitudes and use of evidence between cohorts; Cohort 2 reported statistically greater perceived knowledge of and skill in EBP. CONCLUSIONS: Emphasis on experiential learning in school with reinforcement of skills in clinical learning environments is not sufficient to change graduates' use of evidence. Although the curriculum revision improved perceived knowledge/skill, our study suggests systems or other factors may influence use after graduation. PMID- 26539676 TI - Simulation Strategies to Teach Patient Transfers: Self-Efficacy by Strategy. AB - OBJECTIVE: We evaluated the effects of transfer training-after training in the classroom and in the high-technology simulation laboratory (WISER Center)-on students' perceptions of their self-efficacy for knowledge, skill, and safety in executing dependent transfers. METHOD: After classroom training, occupational therapy students were randomized to three teaching groups on the basis of the amount of participation and observation opportunities provided at the WISER Center-observation dominant, participation dominant, and participation only. RESULTS: The participation-dominant group reported an increase in knowledge self efficacy over time compared with the observation-dominant and participation-only groups. Over time, self-efficacy ratings increased for all students, regardless of group. CONCLUSION: Simulation scenarios implemented at the WISER Center provided a useful adjunct to classroom training in transfer skills. Both participatory and observational experiences contributed to the development of students' perceptions of their ability to manage acutely ill and medically complex patients. PMID- 26539675 TI - Wheelchair Transfer Simulations to Enhance Procedural Skills and Clinical Reasoning. AB - OBJECTIVE: We describe an educational intervention that involved simulation scenarios of medically complex patients to teach transfer training and promote clinical reasoning. METHOD: Scenarios were developed with practitioner input that described (1) a patient who was acutely ill, (2) a critical medical management event that occurred during a bed-to-wheelchair transfer of the patient, and (3) an occupational need. Transfer training, using the scenarios, occurred in a high technology laboratory with SimMan((r)) and a mock hospital suite. Evaluation was based on student performance and perceptions of simulation effectiveness. RESULTS: On average, students completed 66%-88% of the transfer items correctly. Student performance suggested that the simulation scenarios were more difficult than practitioners rated them. Students rated the simulation scenarios as effective teaching tools. CONCLUSION: Scenario use in simulations for transfer training makes a positive curricular contribution to teaching procedural skills and clinical reasoning simultaneously. PMID- 26539677 TI - Perspectives on the Use of Standardized Parents to Teach Collaboration to Graduate Occupational Therapy Students. AB - OBJECTIVE: Pediatric occupational therapy practitioners interview parents on a daily basis to gain important patient information and develop collaborative intervention goals. A standardized parent experience was developed to help master's-level occupational therapy students gain the skills needed to interview parents after their child's traumatic injury. This article describes the pedagogical approach used to develop the standardized parent experience and reports the students' general perspectives related to this assignment. METHOD: Outcome data were collected through focus groups (n = 9) and document review (n = 12) and then analyzed for themes. RESULTS: Two main themes emerged from the data: It felt real and It helped me to think deeper. CONCLUSION: A standardized parent experience may help occupational therapy students develop the habits of mind associated with collaboration. PMID- 26539678 TI - Benefits of Student Engagement in Intervention Research. AB - OBJECTIVE: Accreditation standards require entry-level occupational therapy students to understand, critique, and design research. However, the extent to which students should be embedded in research projects is unclear. The purpose of this study was to understand the benefits of student immersion in research for student learning and research quality. METHOD: Using a multiple case study design, the principal investigator trained six occupational therapy students to implement a manualized intervention with research participants. Learning quizzes, video analysis of research activities, a practical exam, student documentation, an exit interview, and an exit survey identified student learning and research outcomes. RESULTS: Students successfully implemented the study protocols with good reliability (intraclass correlation coefficient = .89) and fidelity (99%). Students also reported improvements in comfort with client interactions, confidence in practice skills, self-efficacy in research, and clinical reasoning. CONCLUSION: Student participation in hands-on research supports researchers in attaining their research goals and provides students with valuable learning experiences. PMID- 26539679 TI - Fieldwork I Program Evaluation of Student Learning Using Goal Attainment Scaling. AB - This article describes a program evaluation of student learning during the Level I fieldwork experience of a master of science in occupational therapy program. We sought to determine the utility of Goal Attainment Scaling (GAS) as a measure of student learning. Over four semesters, from fall 2013 through fall 2014, 240 students completed goal attainment scales for an individualized learning goal for the semester. Using a quantitative pretest-posttest design, we found significant increases in levels of student learning goal attainment during Level I fieldwork. Qualitative data from exit surveys revealed high levels of satisfaction with the program, particularly related to the opportunity to learn a new way of envisioning and writing individualized goals. These findings support the use of GAS as an outcome measure of student learning during fieldwork. PMID- 26539680 TI - Facilitators and Barriers to Learning in Occupational Therapy Fieldwork Education: Student Perspectives. AB - PURPOSE: The purpose of this study was to gain a comprehensive understanding of the facilitators of and barriers to learning within occupational therapy fieldwork education from the perspective of both Canadian and American students. METHOD: A qualitative study using an online open survey format was conducted to gather data from 29 occupational therapy students regarding their fieldwork experiences. An inductive grounded theory approach to content analysis was used. RESULTS: Individual, environmental, educational, and institutional facilitators of and barriers to learning within occupational therapy fieldwork education were identified. CONCLUSION: This study's findings suggest that learning within fieldwork education is a highly individual and dynamic process that is influenced by numerous factors. The new information generated by this study has the potential to positively affect the future design and implementation of fieldwork education. PMID- 26539681 TI - Ability of the National Board for Certification in Occupational Therapy Practice Test to Estimate the Probability of First-Time Pass Status on the National Certification Exam. AB - OBJECTIVE: To estimate the ability of the National Board for Certification in Occupational Therapy (NBCOT) practice test to predict first-time pass status on the NBCOT Occupational Therapist Registered exam. METHOD: Performance ratios for the four NBCOT practice test domains were used to develop a logistic regression model for estimating the probability of first-time pass status on the NBCOT exam. RESULTS: Of 65 students who graduated during academic years 2010-2013, 41 (63%) attained first-time pass status. The logistic regression model was a good fit. The variance explained ranged from 22% to 29%. The odds of first-time no-pass status were associated with performance ratios on Domains 1 and 2 but not Domains 3 and 4. CONCLUSION: To maximize the probability of students' attaining first time pass status, faculty should consider ways to increase their exposure to the tasks and skills required for implementation of intervention plans (Domains 3 and 4). PMID- 26539682 TI - U.S. and Swedish Student Learning Through Online Synchronous International Interactions. AB - There is a continued need to communicate global perspectives in occupational therapy education, but the literature addressing how to incorporate firsthand global experiences into campus learning environments is scant. This article describes how course-based synchronous interactions between U.S. undergraduate occupational science students and Swedish undergraduate occupational therapy students occur via online technology. In a 2014 pilot study, we thematically analyzed students' open-ended survey responses to discern what students learned through the interactive sessions. We also performed a content analysis of four audio-recorded interactive sessions to understand the content and nature of students' learning. Our findings suggest that course-based online synchronous interactions provide a positive way for students to learn about other cultures and global differences in occupational therapy practice. The findings also highlight needs for improvement relative to the structure and aims of the interactive sessions. We relate these findings to the global availability of technology and occupational therapists' cultural competence. PMID- 26539683 TI - National Survey of Fieldwork Educators: Implications for Occupational Therapy Education. AB - OBJECTIVE: The purpose of this study was to gain information on the current status of fieldwork training facilities to understand facilitators of and barriers to fieldwork education, including fieldwork educators' perceptions of benefits, challenges, and valued supports. METHOD: A descriptive, nonexperimental exploratory design was used. A pilot survey was conducted, and a revised online survey, consisting of 49 items, was distributed nationwide in Fall 2013. RESULTS: Opportunity to update practice was the most commonly perceived benefit associated with fieldwork, and workload or time was the greatest perceived challenge. Readiness and high-quality preparation of students by academic programs were the most valued supports. Participants also identified preferred time frames and supervisory models of fieldwork education. CONCLUSION: Interpretation of these data provides valuable information for the profession, notably academic programs, regarding needs and resources to foster collaborative relationships with fieldwork facilities to meet the growing need for fieldwork education. PMID- 26539684 TI - Reliability and Sensitivity to Change of Goal Attainment Scaling in Occupational Therapy Nonclassroom Educational Experiences. AB - Occupational therapy programs are charged with measuring student progress in nonclassroom experiential components (American Occupational Therapy Association, 2012). Currently, the major nonclassroom educational experience is Level II fieldwork. Level II performance is assessed using the Fieldwork Performance Evaluation, which is inappropriate for measuring doctoral-level experiential component achievement. This study's purpose was to determine test-retest reliability and sensitivity of Goal Attainment Scaling (GAS) for assessing skill development in nonclassroom occupational therapy experiences. GAS demonstrated high test-retest reliability for each of the five goals, and we found a significant amount of change on the GAS, with higher scores at the 12-wk than at the 6-wk assessment. Results indicate that the GAS is reliable and sensitive to changes in student performance on Level II fieldwork and may therefore warrant investigation as a valid tool to measure student performance in the entry-level doctoral experiential component. PMID- 26539685 TI - Energizing Occupation as the Center of Teaching and Learning. AB - The concept of occupation has experienced a renewal in the past 3 decades and is widely accepted as the core subject in occupational therapy. Professional education has a critical stewardship role in continually enhancing how occupation is taught and understood to enrich new occupational therapy practitioners' ability to grasp the purpose of the profession and reason clinically in complex practice environments. The authors discuss three questions that frame approaches educators can use to effectively centralize occupation in teaching and learning environments: (1) To what degree is a curriculum and its courses and class sessions subject centered? (2) To what degree do instructional processes create links to occupation? and (3) To what degree do instructional processes expose and promote complex ways of knowing needed for learning occupation? Keeping occupation in the foreground is important to facilitate new research, teaching methods, and curricular relevance to practice. PMID- 26539686 TI - The Next Paradigm Shift in Occupational Therapy Education: The Move to the Entry Level Clinical Doctorate. AB - The occupational therapy profession in the United States is considering another shift in the level of entry-to-practice education. Currently, all accredited U.S. occupational therapy education programs offer graduate-entry master's degrees or clinical doctorates. In 2014, the American Occupational Therapy Association Board of Directors published a position statement supporting the idea of moving all entry-level occupational therapy education programs to the clinical doctorate level by 2025. This article provides an overview of the proposed reasons for doing so and the potential impact of this move on future students, education providers, clients and families, employers, and third-party payers and funding bodies along with the implications for the occupational therapy profession internationally. An open, informed, transparent, multiperspective, comprehensive debate about this education paradigm shift is recommended. In August 2015 the Accreditation Council for Occupational Therapy Education decided that the entry level qualification will remain at both the master's and the doctoral degree; it is anticipated, however, that the move toward the entry-level clinical doctorate will continue. PMID- 26539688 TI - Complementary and Alternative Medicine and Therapy Use in a Diverse New Mexican Population. AB - OBJECTIVE: To describe differences, attitudes, and experiences in use of complementary and alternative medicines and therapy (CAMT) in people living in New Mexico (NM). DESIGN: Cross-sectional survey study. SETTING: Clinics staffed by the University of New Mexico College of Pharmacy faculty between September 2009 and August 2011 in Albuquerque, NM. PARTICIPANTS: Patients 18 years of age or older or parents of patients younger than age 18 years. OUTCOME MEASURES: Descriptive statistics for survey results and mean scores for attitudinal items. Chi-square, t-test, and analysis of variance were used to compare differences between groups across demographic variables. RESULTS: A convenience sample yielded 263 completed surveys. Of the respondents, 62% were male, 39% were single, and 50% were Hispanic. Nearly 56% of respondents used CAMT in the previous 6 months; 38% used CAMT in addition to and 11% used CAMT instead of prescription medications. Average number of CAMT used per respondent was 2.3 +/- 1.6. A majority of respondents indicated that their CAMT use in the previous 6 months was useful, a good idea, easy to use, and likely to continue. CAMT use was significantly higher in female respondents (p = 0.03), those with a higher education level (p < 0.01), and those with a higher household income level (p = 0.03). CONCLUSION: Prevalence of CAMT is high in a diverse population of patients. Older respondents were more likely to use CAMT in addition to prescription medications, and younger respondents were more likely to use CAMT instead of prescription medications. Providers need to consider CAMT use when discussing treatment options with patients. PMID- 26539689 TI - Sleep problems and computer use during work and leisure: Cross-sectional study among 7800 adults. AB - Previous studies linked heavy computer use to disturbed sleep. This study investigates the association between computer use during work and leisure and sleep problems in working adults. From the 2010 round of the Danish Work Environment Cohort Study, currently employed wage earners on daytime schedule (N = 7883) replied to the Bergen insomnia scale and questions on weekly duration of computer use. Results showed that sleep problems for three or more days per week (average of six questions) were experienced by 14.9% of the respondents. Logistic regression analyses, controlled for gender, age, physical and psychosocial work factors, lifestyle, chronic disease and mental health showed that computer use during leisure for 30 or more hours per week (reference 0-10 hours per week) was associated with increased odds of sleep problems (OR 1.83 [95% CI 1.06-3.17]). Computer use during work and shorter duration of computer use during leisure were not associated with sleep problems. In conclusion, excessive computer use during leisure - but not work - is associated with sleep problems in adults working on daytime schedule. PMID- 26539690 TI - Electroanalysis with Membrane Electrodes and Liquid-Liquid Interfaces. PMID- 26539691 TI - One new 19-nor cucurbitane-type triterpenoid from the stems of Momordica charantia. AB - One new 19-nor cucurbitane-type triterpenoid (3beta,9beta,25-trihydroxy-7beta methoxy-19-nor-cucurbita-5,23(E)-diene) (1), together with other six known cucurbitane-type triterpenoids (2-7), were isolated from the stems of Momordica charantia L. The chemical structure of 1 was elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, COSY and ROESY), MS experiments. Using MTT assay, compound 1 exhibited weak cytotoxicity against HL-60, A-549, and SK-BR-3 cell lines with the IC50 values at 27.3, 32.7 and 26.6 MUM, respectively. PMID- 26539692 TI - Assessment of pet exposure by self-report in epidemiological studies of allergy and asthma: a systematic review. AB - OBJECTIVE: In epidemiological studies that aim to investigate the relationship between pet exposure and allergy/asthma, pet exposure is often ascertained by means of a questionnaire, but it is unclear which questionnaire items are used. The objective of this study was to systematically review self-reported pet exposure assessment in questionnaires used in epidemiological studies which explore the associations between pets and allergy/asthma. METHODS: A systematic literature search was conducted in PubMed and papers were selected according to pre-specified eligibility criteria. The pet exposure questions used were classified within a framework including direct pet contact, indirect pet contact (e.g. through carers or grandparents) and avoidance behaviour. Authors were contacted when the questions used were not reported in detail. RESULTS: Ninety six full text papers were systematically reviewed. All studies assessed direct pet contact, but less than half (45%) explicitly assessed whether pets were allowed indoors. The vast majority of studies assessed both pet exposures during the first year of life and after the first year of life. The minority (13%) assessed whether pet(s) were kept at places regularly visited by the child and pet exposure in utero (15%). Even fewer studies assessed indirect contact to pets (n = 8) and avoidance behaviour (n = 10). CONCLUSIONS: In epidemiological studies, the ascertainment of pet exposure through questionnaires appears to vary greatly. This variation might partly explain the inconsistent and contradictory results of the effects of pet exposure on the development of allergy and asthma. PMID- 26539694 TI - Electronic Documentation and Nurse-Patient Interaction. AB - This author explored the culture of nurse-patient interactions associated with electronic bedside documentation. Data were collected through passive participant observation, audiotaping of nurse-patient interactions, and interviews with nurses. Nurses acknowledged that they need to share their attention between the patient and the computer. They stated that prioritizing patients' needs while completing the required electronic documentation was demanding. Stationary computers challenged the logistics of the exchange. Understanding the adaptation of caregiving necessitated by bedside electronic documentation will have a positive impact on developing systems that interface seamlessly with nurses' workflow and encourage patients' active participation in their care. PMID- 26539695 TI - Astrocytes spatially restrict VEGF signaling by polarized secretion and incorporation of VEGF into the actively assembling extracellular matrix. AB - The spatial organization of vascular endothelial growth factor (VEGF) signaling is a key determinant of vascular patterning during development and tissue repair. How VEGF signaling becomes spatially restricted and the role of VEGF secreting astrocytes in this process remains poorly understood. Using a VEGF-GFP fusion protein and confocal time-lapse microscopy, we observed the intracellular routing, secretion and immobilization of VEGF in scratch-activated living astrocytes. We found VEGF to be directly transported to cell-extracellular matrix attachments where it is incorporated into fibronectin fibrils. VEGF accumulated at beta1 integrin containing fibrillar adhesions and was translocated along the cell surface prior to internalization and degradation. We also found that only the astrocyte-derived, matrix-bound, and not soluble VEGF decreases beta1 integrin turnover in fibrillar adhesions. We suggest that polarized VEGF release and ECM remodeling by VEGF secreting cells is key to control the local concentration and signaling of VEGF. Our findings highlight the importance of astrocytes in directing VEGF functions and identify these mechanisms as promising target for angiogenic approaches. PMID- 26539696 TI - The complete mitochondrial genome sequence of Malus hupehensis var. pinyiensis. AB - The complete mitochondrial genome sequence of Malus hupehensis var. pinyiensis, a widely used apple rootstock, was determined using the Illumina high-throughput sequencing approach. The genome is 422,555 bp in length and has a GC content of 45.21%. It is separated by a pair of inverted repeats of 32,504 bp, to form a large single copy region of 213,055 bp and a small single copy region of 144,492 bp. The genome contains 38 protein-coding genes, four pseudogenes, 25 tRNA genes, and three rRNA genes. The genome is 25,608 bp longer than that of M. domestica, and several structural variations between these two mitogenomes were detected. PMID- 26539697 TI - Statin therapy and plasma vitamin E concentrations: A systematic review and meta analysis of randomized placebo-controlled trials. AB - BACKGROUND: Vitamin E is one of the most important natural antioxidants, and its plasma levels are inversely associated with the progression of atherosclerosis. There have been reports suggesting a potential negative effect of statin therapy on plasma vitamin E levels. The aim of this meta-analysis was to determine the impact of statin therapy on plasma vitamin E concentrations. METHODS: PubMed Medline, SCOPUS, Web of Science and Google Scholar databases were searched to identify randomized placebo-controlled trials evaluating the impact of statins on plasma vitamin E concentrations from inception to February 27, 2015. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used to examine the effect of statins on plasma vitamin E concentrations. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analysis was conducted using the leave-one-out method. RESULTS: A meta-analysis of data from 8 randomized treatment arms including 504 participants indicated a significant reduction in plasma vitamin E concentrations following statin treatment (WMD: -16.30%, 95% CI: -16.93, -15.98, p < 0.001). However, cholesterol-adjusted vitamin E concentrations (defined as vitamin E:total cholesterol ratio) were found to be improved by statin therapy (WMD: 29.35%, 95% CI: 24.98, 33.72, p < 0.001). Statin therapy was not associated with any significant alteration in LDL vitamin E content (SMD: 0.003, 95% CI: -0.90, 0.90, p = 0.995). CONCLUSION: Findings of the present study suggest that statin therapy has no negative impact on plasma vitamin E concentrations or LDL vitamin E content. PMID- 26539699 TI - Correction to: Thyroid 2015;25(7):812-822. PMID- 26539698 TI - Literature Review of Gastrointestinal Physiology in the Elderly, in Pediatric Patients, and in Patients with Gastrointestinal Diseases. AB - Oral bioavailability studies during the development of new medical entities or generic drugs are typically performed in healthy volunteers. Approved drug products are, however, used by patients with diverse disease backgrounds, and by pediatric and elderly patients. To provide the knowledge base for assessing the potential effects of age or co-morbidity on the in vivo performance of an orally absorbed, systemically active drug product, the literature regarding the gastrointestinal (GI) physiological characteristics (pH, permeability, and transit time) in children, in the elderly, and in patients with GI diseases (irritable bowel syndrome, ulcerative colitis, and Crohn's disease) is reviewed herein, with the knowledge gaps highlighted. PMID- 26539700 TI - Shrinking the Lymphatic Filariasis Map of Ethiopia: Reassessing the Population at Risk through Nationwide Mapping. AB - BACKGROUND: Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING: A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS: We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale. PMID- 26539701 TI - Drugs-Related Death Soon after Hospital-Discharge among Drug Treatment Clients in Scotland: Record Linkage, Validation, and Investigation of Risk-Factors. AB - We validate that the 28 days after hospital-discharge are high-risk for drugs related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever injectors for 222/290. Hospital-discharge remains a period of increased DRD vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting. PMID- 26539702 TI - Novel combinations of phenotypic biomarkers predict development of epilepsy in the lithium-pilocarpine model of temporal lobe epilepsy in rats. AB - The discovery and validation of biomarkers in neurological and neurodegenerative diseases is an important challenge for early diagnosis of disease and for the development of therapeutics. Epilepsy is often a consequence of brain insults such as traumatic brain injury or stroke, but as yet no biomarker exists to predict the development of epilepsy in patients at risk. Given the complexity of epilepsy, it is unlikely that a single biomarker is sufficient for this purpose, but a combinatorial approach may be needed to overcome the challenge of individual variability and disease heterogeneity. The goal of the present prospective study in the lithium-pilocarpine model of epilepsy in rats was to determine the discriminative utility of combinations of phenotypic biomarkers by examining their ability to predict epilepsy. For this purpose, we used a recent model refinement that allows comparing rats that will or will not develop spontaneous recurrent seizures (SRS) after pilocarpine-induced status epilepticus (SE). Potential biomarkers included in our study were seizure threshold and seizure severity in response to timed i.v. infusion of pentylenetetrazole (PTZ) and behavioral alterations determined by a battery of tests during the three weeks following SE. Three months after SE, video/EEG monitoring was used to determine which rats had developed SRS. To determine whether a biomarker or combination of biomarkers performed better than chance at predicting epilepsy after SE, derived data underwent receiver operating characteristic (ROC) curve analyses. When comparing rats with and without SRS and sham controls, the best intergroup discrimination was obtained by combining all measurements, resulting in a ROC area under curve (AUC) of 0.9592 (P<0.01), indicating an almost perfect discrimination or accuracy to predict development of SRS. These data indicate that a combinatorial biomarker approach may overcome the challenge of individual variability in the prediction of epilepsy. PMID- 26539703 TI - Outcome-centered antiepileptic therapy: Rate, rhythm and relief.: Implementing AAN Epilepsy Quality Measures in clinical practice. AB - Clinicians who manage patients with epilepsy are expected to assess the relevance of clinical trial results to their practice, integrate new treatments into the care algorithm, and implement epilepsy quality measures, with the overall goal of improving patient outcomes. A disease-based clinical framework that helps with choice and combinations of interventions facilitates provision of efficient, cost effective, and high-quality care. This article addresses the current conceptual framework that informs clinical evaluation of epilepsy, explores gaps between development of treatment options, quality measures and clinical goals, and proposes an outcome-centered approach that bridges these gaps with the aim of improving patient and population-level clinical outcomes in epilepsy. PMID- 26539704 TI - Transport of bisphenol-A in sandy aquifer sediment: Column experiment. AB - The present paper aims to study the transport behavior of bisphenol-A (BPA) in sandy aquifer so as to provide important parameters for the prediction and control of contaminant plume in aquifer. Miscible displacement experiments were conducted and the breakthrough curves (BTCs) were simulated using HYDRUS-1D software. The effects of pore-water velocity (10-52 cm h(-1)) and initial concentration (2.5-40 mg L(-1)) on the sorption were also investigated. The BTCs of BPA fit the linear first-order non-equilibrium two-site model. The parameters such as partition coefficient (K(d)), the fraction of instantaneous adsorption on "Type-1" sites (F), the first order sorption rate coefficient for the kinetic non equilibrium (type-2) sites (alpha), the retardation coefficient (R), and sorption capacity (q(column)) were computed. Results showed that BPA transported 0.11-0.83 m with various pore water velocity in sandy sediment column when water flowed 1 m. The sorption of BPA was mainly caused by the instantaneous surface adsorption as F varied from 0.596 to 0.908. The transport velocity of BPA was affected by pore water velocity (v) and followed the linear equation 1/R = 0.0600 + 0.0110v (r(2) = 0.9724). The parameter K(d) were also closely related to v and followed the equation LnK(d) = 1.0023-0.0482v (r(2) = 0.9690). The sorption capacity was more related to the initial BPA concentration (C0) and followed the linear equation q(column) = 0.265 + 0.253C0 (r(2) = 0.9727). The parameter alpha was affected by both v and C0 whereas F was not dramatically affected by both. PMID- 26539705 TI - Historical deposition of persistent organic pollutants in Lake Victoria and two alpine equatorial lakes from East Africa: Insights into atmospheric deposition from sedimentation profiles. AB - Information on historical deposition of persistent organic pollutants (POPs) for African lakes is very limited. We investigated historical deposition trends and sources of POPs in sediment cores from Lakes Victoria (SC1), Bujuku (Buju2) and Mahoma (Maho2). The latter two lakes are situated in the Rwenzori mountain range in western Uganda. SC1 was taken from a central depositional area within the Ugandan part of the lake. Profiles in Buju2 and Maho2 were used as a reference for historical atmospheric deposition. For the post-1940 sediment deposits in SC1, average focusing factor-adjusted fluxes (FFFs) of SigmaDDTs, polychlorinated biphenyls (SigmaPCBs), hexachlorocyclohexanes (SigmaHCHs) and chlordanes (SigmaCHLs) were 390, 230, 210 and 120 ng m(-2) yr(-1). Higher fluxes of SigmaDDTs, SigmaPCBs, and SigmaCHLs were observed in Buju2 and Maho2. The average FFF of HCB in Buju2 was the highest while the values for Maho2 and SC1 were similar. The endosulfan FFFs in SC1 were lower than in the alpine lake cores. Generally, Buju2 was a better reference for historical atmospheric deposition of POPs than Maho2 probably due to distortion of the latter's profile by Lake Mahoma's forested catchment. Profiles of p,p'-DDE, SigmaCHLs and HCB in SC1 were consistent with atmospheric deposition while profiles of PCBs and HCHs were indicative of particle-bound loadings from additional sources. Profiles of endosulfans, DDTs, and chlordanes were consistent with influence of other factors such as anoxia, and dilution. Further studies of spatial resolution of historical deposition, especially in near-shore deposition areas of the lake are recommended. PMID- 26539706 TI - Conceptual design and experiments of electrochemistry-flushing technology for the remediation of historically Cr(VI)-contaminated soil. AB - A conceptual design and experiments, electrochemistry-flushing (E-flushing), using electrochemistry to enhance flushing efficiency for the remediation of Cr(VI)-contaminated soil is presented. The rector contained three compartments vertically superposed. The upper was airtight cathode compartment containing an iron-cathode. The middle was soil layer. The bottom was anode compartment containing an iron-anode and connected to a container by circulation pumps. H2 and OH(-) ions were produced at cathode. H2 increased the gas pressure in cathode compartment and drove flushing solution into soil layer forming flushing process. OH(-) ions entered into soil layer by eletromigration and hydraulic flow to enhance the desorption of Cr(VI). High potential gradient was applied to accelerate the electromigration of desorbed Cr(VI) ions and produced joule heat to increase soil temperature to enhance Cr(VI) desorption. In anode compartment, Fe(2+) ions produced at iron-anode reduced the desorbed Cr(VI) into Cr(3+) ions, which reacted with OH(-) ions forming Cr(OH)3. Experimental results show that Cr(VI) removal efficiency of E-flushing experiments was more than double of flushing experiments and reached the maximum of removal efficiency determined by desorption kinetics. All electrochemistry processes were positively used in E flushing technology. PMID- 26539708 TI - Response to shock load of engineered nanoparticles in an activated sludge treatment system: Insight into microbial community succession. AB - The environmental impacts of the use of engineered nanoparticles (NPs) remain unclear and have attracted increasing concern worldwide. Considering that NPs eventually end up in wastewater treatment systems, the potential impact of ZnO and TiO2 NPs on the activated sludge was investigated using laboratory-scale sequencing batch reactors (SBRs). Short-term (24 h) exposure to 1, 10 and 100 mg/L shock loads of NPs reduced the oxygen uptake rate of the activated sludge by 3.55%-12.51% compared with the controls. In our experiment, the toxicities of TiO2 NPs were higher than those of ZnO NPs as reflected in the inhibition of oxygen utilization in the activated sludge. However, both the short-term (24 h) and long-term (21 days) exposure to ZnO and TiO2 NPs did not adversely affect the pollutant removal of the SBRs. Furthermore, the polymerase chain reaction denaturing gel gradient electrophoresis revealed that the microbial community did not significantly vary after the short-term exposure (24 h) to 1, 10 and 100 mg/L shock loads of NPs; however, the cluster analysis in our experiment revealed that the slight difference caused by the NPs largely depended on exposure time rather than on NP type and NP concentration. The long-term exposure (13 days) to 10 mg/L shock load of ZnO or TiO2 NPs caused no substantial microbial community shifts in the activated sludge. The microbial diversity also showed no significant change when exposed to NPs as revealed by the Shannon-Wiener index. PMID- 26539707 TI - Compound-specific carbon isotopic fractionation during transport of phthalate esters in sandy aquifer. AB - The present paper aims to evaluate the carbon isotopic fractionation of phthalate esters (PAEs) during transport in an sandy aquifer. Breakthrough curves of di methyl phthalate (DMP), di-ethyl phthalate (DEP), and di-n-butyl phthalate (DBP) in mixed solution were determined by miscible displacement experiment, and simulated using HYDRUS-1D software. The stable carbon isotopes (delta(13)C) of 3 PAEs in effluent were analyzed at different times. Results showed that, in the transport process in sandy sediment, PAEs are mainly trapped into the pore space instead of being adsorbed on the surface of particles. At the initial stage of transport, PAEs with lighter carbon tend to run faster in the sandy sediment, and PAEs with heavier carbon run after. However, there is no priority for the transport of PAEs with different carbon isotopes at Stage II with mainly time limited sorption. So the transport-based isotope fractionation occurs in the front area of contaminant plume. This effect may be relevant for interpreting carbon isotope signatures in the real contaminant site. PMID- 26539709 TI - Toxicity interaction between chlorpyrifos, mancozeb and soil moisture to the terrestrial isopod Porcellionides pruinosus. AB - A main source of uncertainty currently associated with environmental risk assessment of chemicals is the poor understanding of the influence of environmental factors on the toxicity of xenobiotics. Aiming to reduce this uncertainty, here we evaluate the joint-effects of two pesticides (chlorpyrifos and mancozeb) on the terrestrial isopod Porcellionides pruinosus under different soil moisture regimes. A full factorial design, including three treatments of each pesticide and an untreated control, were performed under different soil moisture regimes: 25%, 50%, and 75% WHC. Our results showed that soil moisture had no effects on isopods survival, at the levels assessed in this experiment, neither regarding single pesticides nor mixture treatments. Additivity was always the most parsimonious result when both pesticides were present. Oppositely, both feeding activity and biomass change showed a higher sensitivity to soil moisture, with isopods generally showing worse performance when exposed to pesticides and dry or moist conditions. Most of the significant differences between soil moisture regimes were found in single pesticide treatments, yet different responses to mixtures could still be distinguished depending on the soil moisture assessed. This study shows that while soil moisture has the potential to influence the effects of the pesticide mixture itself, such effects might become less important in a context of complex combinations of stressors, as the major contribution comes from its individual interaction with each pesticide. Finally, the implications of our results are discussed in light of the current state of environmental risk assessment procedures and some future perspectives are advanced. PMID- 26539710 TI - Solar photocatalytic degradation of naphthenic acids in oil sands process affected water. AB - Bitumen mining in the Canadian oil sands creates large volumes of oil sands process-affected water (OSPW), the toxicity of which is due in part to naphthenic acids (NAs) and other acid extractable organics (AEO). The objective of this work was to evaluate the potential of solar photocatalysis over TiO2 to remove AEO from OSPW. One day of photocatalytic treatment under natural sunlight (25 MJ/m(2) over ~14 h daylight) eradicated AEO from raw OSPW, and acute toxicity of the OSPW toward Vibrio fischeri was eliminated. Nearly complete mineralization of organic carbon was achieved within 1-7 day equivalents of sunlight exposure, and degradation was shown to proceed through a superoxide-mediated oxidation pathway. High resolution mass spectrometry (HRMS) analysis of oxidized intermediate compounds indicated preferential degradation of the heavier and more cyclic NAs (higher number of double bond equivalents), which are the most environmentally persistent fractions. The photocatalyst was shown to be recyclable for multiple uses, and thus solar photocatalysis may be a promising "green" advanced oxidation process (AOP) for OSPW treatment. PMID- 26539711 TI - Impact of an environmental relevant concentration of 17alpha-ethinylestradiol on the cardiac function of bullfrog tadpoles. AB - This study evaluated if a concentration of 17alpha-ethinylestradiol (EE2 - 10 ng L(-1) for 96 h) normally found in Brazilian surface waters exerts any impact on cardiac function of bullfrog tadpoles (25 Gosner stage), Lithobates catesbeianus. During exposure, the animals' activity level (AL -% of active individuals) was monitored twice a day. Then, the in loco heart rate (f(H) - bpm) was determined, as well as the relative ventricular mass (RVM - % of body mass). Afterwards, cardiac ventricles were mounted for isometric force recordings (CS - mN mm(-2)), and determination of the cardiac pumping capacity (CPC - mN mm(-2) min(-1)). EE2 did not affect tadpoles' AL, although it resulted in a tachycardia in animals exposed to EE2 (f(H) = 66 bpm) when compared to controls (f(H) = 52 bpm), suggesting that EE2 acts directly on the cardiac muscle of tadpoles, rather than being a result of an increased cardiac demand due to a higher activity level (i.e., avoidance response). Additionally, EE2 exerted a positive inotropic response, which resulted in a higher CPC, which occurred independently of an increase in the number of myofibrils of EE2-exposed animals, since RVM remained similar between experimental groups. Thus, the increase on cardiac demand induced by the exposure to EE2 elevates considerably the animal energy expenditure, diverting a large amount of energy that tadpoles could use for their growth and development. These alterations can make amphibians more susceptible to predators and reduce the likelihood to reach reproductive stage. PMID- 26539712 TI - Towards energy positive wastewater treatment by sludge treatment using free nitrous acid. AB - Free nitrous acid (FNA i.e. HNO2) was revealed to be effective in enhancing biodegradability of secondary sludge. Also, nitrite-oxidizing bacteria were found to be more susceptible to FNA than ammonium-oxidizing bacteria. Based on these findings, a novel FNA-based sludge treatment technology is proposed to enhance energy recovery from wastewater/sludge. Energy analysis indicated that the FNA based technology would make wastewater treatment become an energy generating process (yielding energy at 4 kWh/PE/y; kWh/PE/y: kilowatt hours per population equivalent per year), rather than being a large energy consumer that it is today (consuming energy at 24 kWh/PE/y). Importantly, FNA required for the sludge treatment could be produced as a by-product of wastewater treatment. This proposed FNA-based technology is economically and environmentally attractive, and can be easily implemented in any wastewater treatment plants. It only involves the installation of a simple sludge mixing tank. This article presents the concept of the FNA-based technology. PMID- 26539713 TI - The ribosome biogenesis pathway as an early target of benzyl butyl phthalate (BBP) toxicity in Chironomus riparius larvae. AB - Butyl benzyl phthalate (BBP) is a ubiquitous contaminant whose presence in the environment is expected for decades, since it has been extensively used worldwide as a plasticizer in the polyvinyl chloride (PVC) industry and the manufacturing of many other products. In the present study, the interaction of BBP with the ribosome biogenesis pathway and the general transcriptional profile of Chironomus riparius aquatic larvae were investigated by means of changes in the rDNA activity (through the study of the internal transcribed spacer 2, ITS2) and variations in the expression profile of ribosomal protein genes (rpL4, rpL11, and rpL13) after acute 24-h and 48-h exposures to a wide range of BBP doses. Furthermore, cytogenetic assays were conducted to evaluate the transcriptional activity of polytene chromosomes from salivary gland cells, with special attention to the nucleolus and the Balbiani rings (BRs) of chromosome IV. BBP caused a dose and time-dependent toxicity in most of the selected biomarkers, with a general depletion in the gene expression levels and the activity of BR2 after 48-h treatments. At the same time, decondensation and activation of some centromeres took place, while the activity of nucleolus remained unaltered. Withdrawal of the xenobiotic allowed the larvae to reach control levels in the case of rpL4 and rpL13 genes, which were previously slightly downregulated in 24 h tests. These data provide the first evidence on the interaction of BBP with the ribosome synthesis pathways, which results in a significant impairment of the functional activity of ribosomal protein genes. Thus, the depletion of ribosomes would be a long-term effect of BBP-induced cellular damage. These findings may have important implications for understanding the adverse biological effects of BBP in C. riparius, since they provide new sensitive biomarkers of BBP exposure and highlight the suitability of this organism for ecotoxicological risk assessment, especially in aquatic ecosystems. PMID- 26539714 TI - Diversity of Riparian Plants among and within Species Shapes River Communities. AB - Organismal diversity among and within species may affect ecosystem function with effects transmitting across ecosystem boundaries. Whether recipient communities adjust their composition, in turn, to maximize their function in response to changes in donor composition at these two scales of diversity is unknown. We use small stream communities that rely on riparian subsidies as a model system. We used leaf pack experiments to ask how variation in plants growing beside streams in the Olympic Peninsula of Washington State, USA affects stream communities via leaf subsidies. Leaves from red alder (Alnus rubra), vine maple (Acer cinereus), bigleaf maple (Acer macrophyllum) and western hemlock (Tsuga heterophylla) were assembled in leaf packs to contrast low versus high diversity, and deployed in streams to compare local versus non-local leaf sources at the among and within species scales. Leaves from individuals within species decomposed at varying rates; most notably thin leaves decomposed rapidly. Among deciduous species, vine maple decomposed most rapidly, harbored the least algal abundance, and supported the greatest diversity of aquatic invertebrates, while bigleaf maple was at the opposite extreme for these three metrics. Recipient communities decomposed leaves from local species rapidly: leaves from early successional plants decomposed rapidly in stream reaches surrounded by early successional forest and leaves from later successional plants decomposed rapidly adjacent to later successional forest. The species diversity of leaves inconsistently affected decomposition, algal abundance and invertebrate metrics. Intraspecific diversity of leaf packs also did not affect decomposition or invertebrate diversity. However, locally sourced alder leaves decomposed more rapidly and harbored greater levels of algae than leaves sourced from conspecifics growing in other areas on the Olympic Peninsula, but did not harbor greater aquatic invertebrate diversity. In contrast to alder, local intraspecific differences via decomposition, algal or invertebrate metrics were not observed consistently among maples. These results emphasize that biodiversity of riparian subsidies at the within and across species scale have the potential to affect aquatic ecosystems, although there are complex species-specific effects. PMID- 26539715 TI - Spontaneous Behaviors and Wall-Curvature Lead to Apparent Wall Preference in Planarian. AB - The planarian Dugesia japonica tends to stay near the walls of its breeding containers and experimental dishes in the laboratory, a phenomenon called "wall preference". This behavior is thought to be important for environmental adaptation, such as hiding by planarians in nature. However, the mechanisms regulating wall-preference behavior are not well understood, since this behavior occurs in the absence of any particular stimulation. Here we show the mechanisms of wall-preference behavior. Surprisingly, planarian wall-preference behavior was also shown even by the head alone and by headless planarians. These results indicate that planarian "wall-preference" behavior only appears to be a "preference" behavior, and is actually an outcome of spontaneous behaviors, rather than of brain function. We found that in the absence of environmental cues planarians moved basically straight ahead until they reached a wall, and that after reaching a wall, they changed their direction of movement to one tangential to the wall, suggesting that this spontaneous behavior may play a critical role in the wall preference. When we tested another spontaneous behavior, the wigwag movement of the planarian head, using computer simulation with various wigwag angles and wigwag intervals, large wigwag angle and short wigwag interval reduced wall-preference behavior. This indicated that wigwag movement may determine the probability of staying near the wall or leaving the wall. Furthermore, in accord with this simulation, when we tested planarian wall-preference behavior using several assay fields with different curvature of the wall, we found that concavity and sharp curvature of walls negatively impacted wall preference by affecting the permissible angle of the wigwag movement. Together, these results indicate that planarian wall preference may be involuntarily caused by the combination of two spontaneous planarian behaviors: moving straight ahead until reaching a wall and then moving along it in the absence of environmental cues, and wigwag movements of the head. PMID- 26539716 TI - A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter. AB - Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS). PMID- 26539717 TI - Characterization of Pneumococcal Genes Involved in Bloodstream Invasion in a Mouse Model. AB - Streptococcus pneumoniae (the pneumococcus) continues to account for significant morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteremia and meningitis, as well as less serious infections such as sinusitis, conjunctivitis and otitis media. Current polysaccharide vaccines are strictly serotype-specific and also drive the emergence of non-vaccine serotype strains. In this study, we used microarray analysis to compare gene expression patterns of either serotype 4 or serotype 6A pneumococci in the nasopharynx and blood of mice, as a model to identify genes involved in invasion of blood in the context of occult bacteremia in humans. In this manner, we identified 26 genes that were significantly up-regulated in the nasopharynx and 36 genes that were significantly up-regulated in the blood that were common to both strains. Gene Ontology classification revealed that transporter and DNA binding (transcription factor) activities constitute the significantly different molecular functional categories for genes up-regulated in the nasopharynx and blood. Targeted mutagenesis of selected genes from both niches and subsequent virulence and pathogenesis studies identified the manganese-dependent superoxide dismutase (SodA) as most likely to be essential for colonization, and the cell wall associated serine protease (PrtA) as important for invasion of blood. This work extends our previous analyses and suggests that both PrtA and SodA warrant examination in future studies aimed at prevention and/or control of pneumococcal disease. PMID- 26539718 TI - Use of the Nanofitin Alternative Scaffold as a GFP-Ready Fusion Tag. AB - With the continuous diversification of recombinant DNA technologies, the possibilities for new tailor-made protein engineering have extended on an on going basis. Among these strategies, the use of the green fluorescent protein (GFP) as a fusion domain has been widely adopted for cellular imaging and protein localization. Following the lead of the direct head-to-tail fusion of GFP, we proposed to provide additional features to recombinant proteins by genetic fusion of artificially derived binders. Thus, we reported a GFP-ready fusion tag consisting of a small and robust fusion-friendly anti-GFP Nanofitin binding domain as a proof-of-concept. While limiting steric effects on the carrier, the GFP-ready tag allows the capture of GFP or its blue (BFP), cyan (CFP) and yellow (YFP) alternatives. Here, we described the generation of the GFP-ready tag from the selection of a Nanofitin variant binding to the GFP and its spectral variants with a nanomolar affinity, while displaying a remarkable folding stability, as demonstrated by its full resistance upon thermal sterilization process or the full chemical synthesis of Nanofitins. To illustrate the potential of the Nanofitin-based tag as a fusion partner, we compared the expression level in Escherichia coli and activity profile of recombinant human tumor necrosis factor alpha (TNFalpha) constructs, fused to a SUMO or GFP-ready tag. Very similar expression levels were found with the two fusion technologies. Both domains of the GFP-ready tagged TNFalpha were proved fully active in ELISA and interferometry binding assays, allowing the simultaneous capture by an anti TNFalpha antibody and binding to the GFP, and its spectral mutants. The GFP-ready tag was also shown inert in a L929 cell based assay, demonstrating the potent TNFalpha mediated apoptosis induction by the GFP-ready tagged TNFalpha. Eventually, we proposed the GFP-ready tag as a versatile capture and labeling system in addition to expected applications of anti-GFP Nanofitins (as illustrated with previously described state-of-the-art anti-GFP binders applied to living cells and in vitro applications). Through a single fusion domain, the GFP-ready tagged proteins benefit from subsequent customization within a wide range of fluorescence spectra upon indirect binding of a chosen GFP variant. PMID- 26539719 TI - Structural Characterisation of FabG from Yersinia pestis, a Key Component of Bacterial Fatty Acid Synthesis. AB - Ketoacyl-acyl carrier protein reductases (FabG) are ubiquitously expressed enzymes that catalyse the reduction of acyl carrier protein (ACP) linked thioesters within the bacterial type II fatty acid synthesis (FASII) pathway. The products of these enzymes, saturated and unsaturated fatty acids, are essential components of the bacterial cell envelope. The FASII reductase enoyl-ACP reductase (FabI) has been the focus of numerous drug discovery efforts, some of which have led to clinical trials, yet few studies have focused on FabG. Like FabI, FabG appears to be essential for survival in many bacteria, similarly indicating the potential of this enzyme as a drug target. FabG enzymes are members of the short-chain alcohol dehydrogenase/reductase (SDR) family, and like other SDRs, exhibit highly conserved secondary and tertiary structures, and contain a number of conserved sequence motifs. Here we describe the crystal structures of FabG from Yersinia pestis (YpFabG), the causative agent of bubonic, pneumonic, and septicaemic plague, and three human pandemics. Y. pestis remains endemic in many parts of North America, South America, Southeast Asia, and Africa, and a threat to human health. YpFabG shares a high degree of structural similarity with bacterial homologues, and the ketoreductase domain of the mammalian fatty acid synthase from both Homo sapiens and Sus scrofa. Structural characterisation of YpFabG, and comparison with other bacterial FabGs and the mammalian fatty acid synthase, provides a strong platform for virtual screening of potential inhibitors, rational drug design, and the development of new antimicrobial agents to combat Y. pestis infections. PMID- 26539721 TI - Evaluation of the Expanded Criteria of Endoscopic Submucosal Dissection for Early Gastric Cancers: A Meta-Analysis. AB - BACKGROUND: In 2010, undifferentiated early-stage gastric cancers (EGCs; <=1 cm and confined to the mucosa) were included in the expanded criteria for endoscopic submucosal dissection (ESD), as established by the Japanese Gastric Cancer Association. OBJECTIVE: To evaluate the safety and efficacy of the newly expanded criteria of ESD for EGCs. METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies published between January 1, 2010 and July 10, 2014. These studies were collected by 2 authors and then analyzed with RevMan 5.0. RESULTS: Six studies including 6,687 patients were identified. Compared to the standard group (SG), the expanded group (EG) had higher bleeding (OR 1.66; 95% CI 1.02-2.68), perforation (OR 2.03; 95% CI 1.25-3.31), positive lateral margin rates (OR 16.88; 95% CI 3.83-74.5) and lower en bloc resection rate (OR 0.48; 95% CI 0.34-0.70). The local recurrence (OR 2.46; 95% CI 0.31-19.23) and total survival rates (OR 0.92; 95% CI 0.76-1.12) between the 2 groups were not statistically different. CONCLUSIONS: Considering the similar rates of local recurrence and total survival between the SG and EG, the use of ESD for the management of EGCs that meet the expanded criteria could be considered a safe and effective treatment method. PMID- 26539720 TI - Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration. AB - Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFkappaB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management. PMID- 26539722 TI - Forecasting Natural Gas Prices Using Wavelets, Time Series, and Artificial Neural Networks. AB - Following the unconventional gas revolution, the forecasting of natural gas prices has become increasingly important because the association of these prices with those of crude oil has weakened. With this as motivation, we propose some modified hybrid models in which various combinations of the wavelet approximation, detail components, autoregressive integrated moving average, generalized autoregressive conditional heteroskedasticity, and artificial neural network models are employed to predict natural gas prices. We also emphasize the boundary problem in wavelet decomposition, and compare results that consider the boundary problem case with those that do not. The empirical results show that our suggested approach can handle the boundary problem, such that it facilitates the extraction of the appropriate forecasting results. The performance of the wavelet hybrid approach was superior in all cases, whereas the application of detail components in the forecasting was only able to yield a small improvement in forecasting performance. Therefore, forecasting with only an approximation component would be acceptable, in consideration of forecasting efficiency. PMID- 26539724 TI - Interactions Increase Forager Availability and Activity in Harvester Ants. AB - Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated. PMID- 26539725 TI - Five Questions about Mycoviruses. PMID- 26539726 TI - Shoulder complex linkage mechanism for humanlike musculoskeletal robot arms. AB - The shoulder complex in the human body consists of the scapula, clavicle, humerus, and thorax and bears the load imposed by arm movements while at the same time realizing a wide range of motions. To mimic and exploit its role, several musculoskeletal robot arms with shoulder complex mechanisms have been developed. However, although many research groups have tried to design the structures using links and joints that faithfully correspond to the bones and joints in the human shoulder complex, its function has not been successfully reproduced because biologically plausible designs seriously compromise engineering plausibility. In this paper, we propose a linkage mechanism that can reproduce complex three dimensional scapulo movements and considers the trade-off between biological and engineering plausibilities. Subsequently, the design was validated by driving the mechanism using pneumatic artificial muscles (PAMs) placed similarly to muscles in humans. Further, we present experiments in which the robot was controlled by surface electromyographic signals from a human. We show that the proposed design, due to its kinematic similarity with human musculoskeletal systems, eases the conversion between the surface electromyogram signals and the PAMs control inputs. PMID- 26539727 TI - Anteaglonialides A-F and Palmarumycins CE(1)-CE(3) from Anteaglonium sp. FL0768, a Fungal Endophyte of the Spikemoss Selaginella arenicola. AB - Anteaglonialides A-F (1-6), bearing a spiro[6-(tetrahydro-7-furanyl)cyclohexane 1,2'-naphtho[1,8-de][1,3]-dioxin]-10-one skeleton, three new spirobisnaphthalenes, palmarumycins CE1-CE3 (7-9), nine known palmarumycin analogues, palmarumycins CP5 (10), CP4a (11), CP3 (12), CP17 (13), CP2 (14), and CP1 (15), CJ-12,371 (16), 4-O-methyl CJ-12,371 (17), and CP4 (18), together with a possible artifact, 4a(5)-anhydropalmarumycin CE2 (8a), and four known metabolites, O-methylherbarin (19), herbarin (20), herbaridine B (21), and hyalopyrone (22), were encountered in a cytotoxic extract of a potato dextrose agar culture of Anteaglonium sp. FL0768, an endophytic fungus of the sand spikemoss, Selaginella arenicola. The planar structures and relative configurations of the new metabolites 1-9 were elucidated by analysis of extensive spectroscopic data, and the absolute configuration of 1 was determined by the modified Mosher's ester method. Application of the modified Mosher's ester method combined with the NOESY data resulted in revision of the absolute configuration previously proposed for 10. Co-occurrence of 1-6 and 7-18 in this fungus led to the proposal that the anteagloniolides may be biogenetically derived from palmarumycins. Among the metabolites encountered, anteaglonialide F (6) and known palmarumycins CP3 (12) and CP1 (15) exhibited strong cytotoxic activity against the human Ewing's sarcoma cell line CHP-100, with IC50 values of 1.4, 0.5, and 1.6 MUM, respectively. PMID- 26539729 TI - Use of Nonequilibrium Work Methods to Compute Free Energy Differences Between Molecular Mechanical and Quantum Mechanical Representations of Molecular Systems. AB - Carrying out free energy simulations (FES) using quantum mechanical (QM) Hamiltonians remains an attractive, albeit elusive goal. Renewed efforts in this area have focused on using "indirect" thermodynamic cycles to connect "low level" simulation results to "high level" free energies. The main obstacle to computing converged free energy results between molecular mechanical (MM) and QM (DeltaA(MM >QM)), as recently demonstrated by us and others, is differences in the so-called "stiff" degrees of freedom (e.g., bond stretching) between the respective energy surfaces. Herein, we demonstrate that this problem can be efficiently circumvented using nonequilibrium work (NEW) techniques, i.e., Jarzynski's and Crooks' equations. Initial applications of computing DeltaA(NEW)(MM->QM), for blocked amino acids alanine and serine as well as to generate butane's potentials of mean force via the indirect QM/MM FES method, showed marked improvement over traditional FES approaches. PMID- 26539730 TI - Proteomic identification of prognostic tumour biomarkers, using chemotherapy induced cancer-associated fibroblasts. AB - Cancer cells grow in highly complex stromal microenvironments, which through metabolic remodelling, catabolism, autophagy and inflammation nurture them and are able to facilitate metastasis and resistance to therapy. However, these changes in the metabolic profile of stromal cancer-associated fibroblasts and their impact on cancer initiation, progression and metastasis are not well-known. This is the first study to provide a comprehensive proteomic portrait of the azathioprine and taxol-induced catabolic state on human stromal fibroblasts, which comprises changes in the expression of metabolic enzymes, myofibroblastic differentiation markers, antioxidants, proteins involved in autophagy, senescence, vesicle trafficking and protein degradation, and inducers of inflammation. Interestingly, many of these features are major contributors to the aging process. A catabolic stroma signature, generated with proteins found differentially up-regulated in taxol-treated fibroblasts, strikingly correlates with recurrence, metastasis and poor patient survival in several solid malignancies. We therefore suggest the inhibition of the catabolic state in healthy cells as a novel approach to improve current chemotherapy efficacies and possibly avoid future carcinogenic processes. PMID- 26539731 TI - Distribution of blood types in a sample of 245 New Zealand non-purebred cats. AB - AIMS: To determine the distribution of feline blood types in a sample of non pedigree, domestic cats in New Zealand, whether a difference exists in this distribution between domestic short haired and domestic long haired cats, and between the North and South Islands of New Zealand; and to calculate the risk of a random blood transfusion causing a severe transfusion reaction, and the risk of a random mating producing kittens susceptible to neonatal isoerythrolysis. METHODS: The results of 245 blood typing tests in non-pedigree cats performed at the New Zealand Veterinary Pathology (NZVP) and Gribbles Veterinary Pathology laboratories between the beginning of 2009 and the end of 2014 were retrospectively collated and analysed. Cats that were identified as domestic short or long haired were included. For the cats tested at Gribbles Veterinary Pathology 62 were from the North Island, and 27 from the South Island. RESULTS: The blood type distribution differed between samples from the two laboratories (p=0.029), but not between domestic short and long haired cats (p=0.50), or between the North and South Islands (p=0.76). Of the 89 cats tested at Gribbles Veterinary Pathology, 70 (79%) were type A, 18 (20%) type B, and 1 (1%) type AB; for NZVP 139/156 (89.1%) cats were type A, 16 (10.3%) type B, and 1 (0.6%) type AB. It was estimated that 18.3-31.9% of random blood transfusions would be at risk of a transfusion reaction, and neonatal isoerythrolysis would be a risk in 9.2-16.1% of random matings between non-pedigree cats. CONCLUSIONS: The results from this study suggest that there is a high risk of complications for a random blood transfusion between non-purebred cats in New Zealand. Neonatal isoerythrolysis should be considered an important differential diagnosis in illness or mortality in kittens during the first days of life. PMID- 26539732 TI - Chronic Intermittent Hypoxia and Blood Pressure: Is There Risk for Hypertension in Healthy Individuals? AB - AIM: The aim of the current study was to assess a year-long impact of chronic intermittent exposure to hypoxia on blood pressure (BP) in healthy working middle aged adults. MATERIALS AND METHODS: Data from pre-employment and annual screening of high-altitude mining company (elevation 4000 meters above sea level) were obtained for 472 workers aged 34.1 +/- 7.8 years, working 2-week shifts, followed by 2 weeks of rest at low altitude (cumulative exposure 6 months). Overall systolic, diastolic BP change (DeltaBP) were calculated, and tested in multivariate regression models in the entire group, as well as in different strata of BP. RESULTS: Baseline systolic BP reduced from 123.2 +/- 11.3 to 116.3 +/- 13.1 mmHg (DeltaBP 6.8 mmHg), diastolic BP from 76.7 +/- 8.4 to 74.9 +/- 8.4 mmHg (DeltaBP -1.7 mmHg) (p < 0.001), both measured at low altitude before and after one year of exposure to chronic intermittent hypoxia. The greater the baseline BP, the more pronounced was BP decrease. In the most prevalent combined group of normal and high normal BP, both systolic and diastolic BP reduced after one year of high altitude exposure (p < 0.01). In multivariate adjusted models, none of exposures of interest were associated with DeltaBP. CONCLUSIONS: One-year intermittent exposure to hypobaric hypoxia in new hires for high-altitude mining company was not associated with BP increase. PMID- 26539734 TI - How Much Nonclinical Safety Data Are Required for a Clinical Study in Ophthalmology? AB - Planning the nonclinical development program for an ophthalmic product requires first an understanding of how the drug will be used in the clinic-topical, injected, relatively short duration of testing, chronic testing, and what is already known about the drug. In some cases, when the drug is being repurposed or reformulated to allow for the same or different route of ocular administration, the requirements will be very different than for a first-in-class, novel drug. In general, ICH guidances have relatively little direction with respect to ophthalmology. Sponsors are encouraged to make use of meetings with the FDA, particularly for unusual situations, given this lack of specific ICH direction. In this article we describe the range of nonclinical studies required in our experience-pharmacology, pharmacokinetics and toxicology, with attention to the stage of clinical development and duration of treatment. As well, we discuss the coordination of effort with pharmaceutics researchers on drug substance and drug product. PMID- 26539733 TI - Stable Carbon Isotope Fractionation during Bacterial Acetylene Fermentation: Potential for Life Detection in Hydrocarbon-Rich Volatiles of Icy Planet(oid)s. AB - We report the first study of stable carbon isotope fractionation during microbial fermentation of acetylene (C2H2) in sediments, sediment enrichments, and bacterial cultures. Kinetic isotope effects (KIEs) averaged 3.7 +/- 0.50/00 for slurries prepared with sediment collected at an intertidal mudflat in San Francisco Bay and 2.7 +/- 0.20/00 for a pure culture of Pelobacter sp. isolated from these sediments. A similar KIE of 1.8 +/- 0.70/00 was obtained for methanogenic enrichments derived from sediment collected at freshwater Searsville Lake, California. However, C2H2 uptake by a highly enriched mixed culture (strain SV7) obtained from Searsville Lake sediments resulted in a larger KIE of 9.0 +/- 0.70/00. These are modest KIEs when compared with fractionation observed during oxidation of C1 compounds such as methane and methyl halides but are comparable to results obtained with other C2 compounds. These observations may be useful in distinguishing biologically active processes operating at distant locales in the Solar System where C2H2 is present. These locales include the surface of Saturn's largest moon Titan and the vaporous water- and hydrocarbon-rich jets emanating from Enceladus. KEY WORDS: Acetylene-Fermentation-Isotope fractionation-Enceladus Life detection. PMID- 26539735 TI - A long natural-antisense RNA is accumulated in the conidia of Aspergillus oryzae. AB - Analysis of expressed sequence tag libraries from various culture conditions revealed the existence of conidia-specific transcripts assembled to putative conidiation-specific reductase gene (csrA) in Aspergillus oryzae. However, the all transcripts were transcribed with opposite direction to the gene csrA. The sequence analysis of the transcript revealed that the RNA overlapped mRNA of csrA with 3'-end, and did not code protein longer than 60 amino acid residues. We designated the transcript Conidia Specific Long Natural-antisense RNA (CSLNR). The real-time PCR analysis demonstrated that the CSLNR is conidia-specific transcript, which cannot be transcribed in the absence of brlA, and the amount of CSLNR was much more than that of the transcript from csrA in conidia. Furthermore, the csrA deletion, also lacking coding region of CSLNR in A. oryzae reduced the number of conidia. Overexpression of CsrA demonstrated the inhibition of growth and conidiation, while CSLNR did not affect conidiation. PMID- 26539736 TI - First-rib stress fracture in two adolescent swimmers: a case report. AB - First-rib stress fractures have been described in adolescent athletes in various sports, with only one prior case report of first-rib stress fractures in an adolescent female swimmer. There is a need for research on the cause, management, and prevention of these injuries as they lead to significant morbidity and critical time away from sport for these aspiring athletes. We aimed to describe first-rib stress fractures as a potential cause for non-specific atraumatic chronic shoulder pain in adolescent swimmers and to discuss the different presentations, unique risk factors, treatment, and potential injury prevention strategies of such fractures. We discussed two such cases which were successfully treated with activity modification with restriction of all overhead activity, gradually progressive physical therapy and a return to swimming protocol. First rib stress fractures can vary in presentation and should be in the differential diagnosis in adolescent swimmers with chronic shoulder pain. These injuries can be successfully managed with rest from overhead activities and physical therapy. Gradual return to competitive swimming can be achieved even with non-union of a first-rib stress fracture. Emphasis on balanced strength training in different muscle groups and proper swimming technique is essential to prevent these injuries. PMID- 26539737 TI - Estimation of genetic parameters related to eggshell strength using random regression models. AB - This study examined the changes in eggshell strength and the genetic parameters related to this trait throughout a hen's laying life using random regression. The data were collected from a crossbred population between 2011 and 2014, where the eggshell strength was determined repeatedly for 2260 hens. Using random regression models (RRMs), several Legendre polynomials were employed to estimate the fixed, direct genetic and permanent environment effects. The residual effects were treated as independently distributed with heterogeneous variance for each test week. The direct genetic variance was included with second-order Legendre polynomials and the permanent environment with third-order Legendre polynomials. The heritability of eggshell strength ranged from 0.26 to 0.43, the repeatability ranged between 0.47 and 0.69, and the estimated genetic correlations between test weeks was high at > 0.67. The first eigenvalue of the genetic covariance matrix accounted for about 97% of the sum of all the eigenvalues. The flexibility and statistical power of RRM suggest that this model could be an effective method to improve eggshell quality and to reduce losses due to cracked eggs in a breeding plan. PMID- 26539738 TI - Use of Social Networking Sites and Risk of Cyberbullying Victimization: A Population-Level Study of Adolescents. AB - Social networking sites (SNSs) have gained considerable popularity among youth in recent years; however, there is a noticeable paucity of research examining the association between the use of these web-based platforms and cyberbullying victimization at the population level. This study examines the association between the use of SNSs and cyberbullying victimization using a large-scale survey of Canadian middle and high school students. Data on 5,329 students aged 11-20 years were derived from the 2013 Ontario Student Drug Use and Health Survey. Logistic regression was used to examine the relationship between the use of SNSs and cyberbullying victimization while adjusting for covariates. Overall, 19 percent of adolescents were cyberbullied in the past 12 months. Adolescents who were female, younger, of lower socioeconomic status, and who used alcohol or tobacco were at greater odds of being cyberbullied. The use of SNSs was associated with an increased risk of cyberbullying victimization in a dose response manner (p-trend <0.001). Gender was not a significant moderator of the association between use of SNSs and being cyberbullied. Results from this study underscore the need for raising awareness and educating adolescents on effective strategies to prevent cyberbullying victimization. PMID- 26539739 TI - Lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients. AB - BACKGROUND: It is widely accepted that chronic renal failure is associated with severe alterations of immune system. However, few studies looked into the immune alteration in earlier stage of chronic kidney disease (CKD) patients. To characterize immune defect in CKD patients, we performed lymphocyte subset analysis and explored its relationship to renal function in this population. METHODS: 472 CKD patients were enrolled in this study. Lymphocyte subsets (CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD56(+)CD16(+)) were determined by flow cytometry. Clinical and laboratory data were collected. Patterns of immune cells in different stages of CKD were compared. Multivariate linear regression was used to evaluate the relationship between lymphocyte subset group and renal function. Correlation analysis was used to assess the relationship between lymphocyte subset and other clinical and laboratory data. RESULTS: Decreased lymphocyte counts occurred long before the end stage of renal disease. Increased NK cell percentage was negatively related to estimated glomerular filtration rate (eGFR) (r = -0.259, p < 0.001) while B cell percentage was positively related to eGFR (r = 0.249, p < 0.001). Further multivariate linear regression showed increased B cell percentage (beta = 16.470, 95%CI [1.018-31.922], p = 0.037) and decreased NK cell percentage (beta = -10.659, 95%CI [-20.063 to -1.254], p = 0.026) were independently correlated with higher eGFR, respectively. Patients with lower NK cell percentage and higher B cell percentage tended to have the best renal function. CONCLUSIONS: Lymphocyte depletion and subset alteration occurred during the progress of CKD. Further studies are needed to clarify the role of immune system in CKD and to expand our knowledge about the effect of uremia on the structure and function of immune system. PMID- 26539740 TI - A suPAR Biomarker for Chronic Kidney Disease. PMID- 26539742 TI - Mesoscale Simulations and Experimental Studies of pH-Sensitive Micelles for Controlled Drug Delivery. AB - The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH >6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties. PMID- 26539743 TI - Rhodium(III)-Catalyzed Direct Cyanation of Aromatic C-H Bond to Form 2 (Alkylamino)benzonitriles Using N-Nitroso As Directing Group. AB - 2-(Alkylamino)benzonitriles were synthesized via a rhodium-catalyzed cyanation on the aryl C-H bond and subsequent denitrosation of N-nitrosoarylamines using a removable nitroso as the directing group, in which N-cyano-N-phenyl-p methylbenzenesulfonamide (NCTS) was used as the "CN" source. Various substituents on the aryl ring and amino group of N-nitrosoarylamines tolerated the reaction, and the corresponding products were achieved in moderate to good yields. PMID- 26539741 TI - Next generation protein based Streptococcus pneumoniae vaccines. AB - All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of Spn. One of the most universal and comprehensive approaches of identifying novel vaccine candidates is the investigation of human sera from different disease stages of natural infections. Antigens that are robustly reactive in preliminary human serum screening constitute a pathogen-specific antigenome. This strategy has identified a number of Spn protein vaccine candidates that are moving forward in human clinical trials. PMID- 26539744 TI - Exploring communication and interaction skills at work among participants in individual placement and support. AB - BACKGROUND: Not all people with severe mental illness who attend Individual Placement and Support (IPS) gain and keep their jobs or work full time. Research has indicated a relationship between social disabilities and work performance in this group, and that support provided is often directed towards the social work environment. However, relationships between social skills performed in an authentic work setting and vocational outcomes have not been explored. OBJECTIVES: To explore relationships between social communication and interaction skills and vocational outcomes among IPS service users in a Swedish context. MATERIAL AND METHODS: Twenty-nine participants were appraised with the Assessment of Communication and Interaction Skills (ACIS-S) instrument, and their vocational data were registered. Correlations were estimated using Spearman's rho test with Bonferroni corrections at item level. RESULTS: Better communication and interaction skills were significantly correlated with increased working hours (rs = 0.64) and higher income (rs = 0.45). Increased working hours were related to assuming postures, asking questions, sharing information, and sustaining conversation in an appropriate manner. CONCLUSION: The results indicate that occupational therapists need to focus on social skills and accommodation of the social work environment in order to promote sustainable working careers among people with severe mental illness. PMID- 26539745 TI - The complete mitochondrial genome sequence of a cavefish Sinocyclocheilus anshuiensis (Cypriniformes: Cyprinidae). AB - Sinocyclocheilus anshuiensis is a special cavefish that lives in the Southwestern China with many specific regressive features, such as rudimentary eyes and scales, and loss of pigmentation. In this study, we performed sequencing and assembly of its complete mitochondrial genome. We confirmed that total length of the mitochondrion is 16 618 bp with an AT ratio of 55.4%. The complete mitochondrial genome contains 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs and a 963 bp control region. Our current data provide important resources for the research of cavefish mitochondrial evolution and energy metabolism. PMID- 26539746 TI - Wetting behavior on hexagonally close-packed polystyrene bead arrays with different topographies. AB - Herein, we investigated the wetting behavior of hexagonally close-packed polystyrene bead arrays with different bead diameters and surface flatness. The contact angle was found to be influenced by the surface roughness as well as the contact area of the polystyrene bead array with a water droplet. PMID- 26539747 TI - Correlates of Objectively Measured Physical Activity Among Norwegian Older Adults: The Generation 100 Study. AB - The aim of this study was to identify how demographics, physical activity (PA) history, and environmental and biological correlates are associated with objectively measured PA among older adults. PA was assessed objectively in 850 older adults (70-77 years, 48% females) using the ActiGraph GT3X+ activity monitor. Hierarchical multiple regression analysis was used to identify important PA correlates. The included correlates explained 27.0% of the variance in older adult's PA. Cardiorespiratory fitness (CRF), gender, and season were the most important correlates, explaining 10.1%, 3.9%, and 2.7% of the variance, respectively. PA was positively associated with CRF, females were more physically active than males, and PA increased in warmer months compared with colder months. This is, to our knowledge, the largest study of PA correlates in older adults that has combined objectively measured PA and CRF. Our findings provide new knowledge about how different correlates are associated with PA. PMID- 26539748 TI - Exploring Crystal Phase Switching in GaP Nanowires. AB - The growth of wurtzite/zincblende (WZ and ZB, respectively) superstructures opens new avenues for band structure engineering and holds the promise of digitally controlling the energy spectrum of quantum confined systems. Here, we study growth kinetics of pure and thus defect-free WZ/ZB homostructures in GaP nanowires with the aim to obtain monolayer control of the ZB and WZ segment lengths. We find that the Ga concentration and the supersaturation in the catalyst particle are the key parameters determining growth kinetics. These parameters can be tuned by the gallium partial pressure and the temperature. The formation of WZ and ZB can be understood with a model based on nucleation either at the triple phase line for the WZ phase or in the center of the solid-liquid interface for the ZB phase. Furthermore, the observed delay/offset time needed to induce WZ and ZB growth after growth of the other phase can be explained within this framework. PMID- 26539749 TI - The primatologist as a behavioral engineer. AB - The field of primate behavior management has had only limited success in preventing and treating abnormal behaviors, such as stereotypy and self-injury, in captive non-human primates (NHP). In contrast, applied behavior analysts have had great success in treating similar topographies of behavior in human clinical settings. By adapting and adopting the behavioral principles and methodologies commonly used by applied behavior analysts, primatologists may be able to develop more effective ways to analyze, reduce, and prevent these aberrant behaviors in NHP. This article reviews studies that have used behavior analytic techniques to successfully address problem behaviors in NHP. Additionally, relevant literature from the field of applied behavior analysis is reviewed to illustrate how adopting a theoretical framework that emphasizes the determination of the underlying operant functions of behavior could lead to new behavioral technologies and advance the field of captive primate management. Am. J. Primatol. 79:e22500, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26539750 TI - Applications of Molecularly Imprinted Polymer Nanoparticles and Their Advances toward Industrial Use: A Review. PMID- 26539752 TI - A Nonfullerene Small Molecule Acceptor with 3D Interlocking Geometry Enabling Efficient Organic Solar Cells. AB - A new 3D nonfullerene small-molecule acceptor is reported. The 3D interlocking geometry of the small-molecule acceptor enables uniform molecular conformation and strong intermolecular connectivity, facilitating favorable nanoscale phase separation and electron charge transfer. By employing both a novel polymer donor and a nonfullerene small-molecule acceptor in the solution-processed organic solar cells, a high-power conversion efficiency of close to 6% is demonstrated. PMID- 26539751 TI - High-Content Assay Multiplexing for Toxicity Screening in Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Hepatocytes. AB - Cell-based high-content screening (HCS) assays have become an increasingly attractive alternative to traditional in vitro and in vivo testing in pharmaceutical drug development and toxicological safety assessment. The time- and cost-effectiveness of HCS assays, combined with the organotypic nature of human induced pluripotent stem cell (iPSC)-derived cells, open new opportunities to employ physiologically relevant in vitro model systems to improve screening for potential chemical hazards. In this study, we used two human iPSC types, cardiomyocytes and hepatocytes, to test various high-content and molecular assay combinations for their applicability in a multiparametric screening format. Effects on cardiomyocyte beat frequency were characterized by calcium flux measurements for up to 90 min. Subsequent correlation with intracellular cAMP levels was used to determine if the effects on cardiac physiology were G-protein coupled receptor dependent. In addition, we utilized high-content cell imaging to simultaneously determine cell viability, mitochondrial integrity, and reactive oxygen species (ROS) formation in both cell types. Kinetic analysis indicated that ROS formation is best detectable 30 min following initial treatment, whereas cytotoxic effects were most stable after 24 h. For hepatocytes, high-content imaging was also used to evaluate cytotoxicity and cytoskeletal integrity, as well as mitochondrial integrity and the potential for lipid accumulation. Lipid accumulation, a marker for hepatic steatosis, was most reliably detected 48 h following treatment with test compounds. Overall, our results demonstrate how a compendium of assays can be utilized for quantitative screening of chemical effects in iPSC cardiomyocytes and hepatocytes and enable rapid and cost efficient multidimensional biological profiling of toxicity. PMID- 26539753 TI - Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015. AB - The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapiens-wt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus. PMID- 26539755 TI - Maternal separation and early stress cause long-lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats. AB - A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 * 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. (c) 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016. PMID- 26539754 TI - Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IV: Depression. AB - OBJECTIVE: To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression. METHODS: The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a three member content expert panel, and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. RESULTS: We present an algorithm and supportive materials to help guide the care of older adults with depression, an important contributor to CLBP. The case illustrates an example of a complex clinical presentation in which depression was an important contributor to symptoms and disability in an older adult with CLBP. CONCLUSIONS: Depression is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatments can be planned and implemented. PMID- 26539756 TI - Isolation and identification of bioactive compounds from chloroform fraction of methanolic extract of Carissa opaca roots. AB - Carissa opaca is a shrub known for its variety of medicinal applications. This study reports isolation and identification of four chemical compounds from its roots for the first time. The methanolic extract of the roots was fractionated into various solvents with increasing polarity. Chloroform fraction was subjected to column and thin layer chromatography to ultimately yield 2H cyclopropanaphthalene-2-one, 7-hydroxy-6-methoxy-2H-1-benzopyran-2-one, 3-(4 methoxyphenyl)-2,6-dimethylbenzofuran and 5(1H)-azulenone, 2,4,6,7,8,8a-hexahydro 3,8-dimethyl-4-(1-methylethylidene)-,(8S-cis). They were identified by GC-MS analysis. The compounds exhibited considerable antimicrobial activities against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger with zones of inhibition ranging from 10 to 13 mm as compared to the standard drug amoxicillin with zones of inhibition 13-17 mm under the similar conditions. In conclusion, the roots of C. opaca can provide new leads for future antimicrobial drugs. PMID- 26539757 TI - Asthma Control Test and Asthma Control Questionnaire: factorial validity, reliability and correspondence in assessing status and change in asthma control. AB - OBJECTIVE: This study examined the factor structures and reliabilities of the Asthma Control Test (ACT) and the Asthma Control Questionnaire (ACQ-7; ACQ-6) and the correspondence between them in assessing both level and change in asthma control. METHODS: Lung function and questionnaire data for ACT and ACQ were assessed in 113 asthma patients at the beginning (T1) and the end (T2) of inpatient rehabilitation. Confirmatory factor analyses, composite reliability coefficients, Pearson correlations, Cohen's Kappa and positive/negative agreements were computed. RESULTS: Unidimensional factor structure was confirmed for ACT. For ACQ configural invariance (i.e. same factor structure) over time could not be established. Furthermore, in ACQ-7, FEV1 showed no relation to the latent factor. Reliability estimates were 0.86-0.88 (ACT), 0.88-0.92(ACQ-6) and 0.81-0.86 (ACQ-7). Pearson correlations between ACT and ACQ were between 0.75 and 0.90 and tended to be higher at T2. If the aim is to identify patients with either not well-controlled asthma or change in asthma control, concordance was at least moderate (Kappa = 0.52-0.72). Correspondence tended to be lower in identifying patients with well-controlled asthma (Kappa = 0.30-0.79). In some circumstances, ACQ-6 showed higher agreement with ACT than did ACQ-7. CONCLUSIONS: ACT is a unidimensional measure, but factor structure of ACQ remains unclear. Correspondence between ACT and ACQ depends on the aim of the assessment. Including FEV1 in the assessment of asthma control level even lowers reliability of ACQ and concordance with ACT. Our results support GINA (2014) in conceptualizing FEV1 as a risk factor for poor asthma outcome instead of an indicator of level of asthma control. PMID- 26539758 TI - Epitaxial Growth of Intermetallic MnPt Films on Oxides and Large Exchange Bias. AB - High-quality epitaxial growth of inter-metallic MnPt films on oxides is achieved, with potential for multiferroic heterostructure applications. Antisite-stabilized spin-flipping induces ferromagnetism in MnPt films, although it is robustly antiferromagnetic in bulk. Moreover, highly ordered antiferromagnetic MnPt films exhibit superiorly large exchange coupling with a ferromagnetic layer. PMID- 26539759 TI - Complete mitochondrial genome of the Chinese hwamei (Garrulax canorus). AB - Chinese hwamei (Garrulax canorus) is native to Eastern Asia, which is a member of Leiothrichidae, Passeriformes. In this study, the complete mitochondrial genome of G. canorus was sequenced. The genome is 17 828 bp in length and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 control regions. Phylogenetic analysis demonstrated that the mitogenomic sequence of G. canorus was most closely related to the sequences from other species of Garrulax. PMID- 26539760 TI - Does Group-Level Commitment Predict Employee Well-Being?: A Prospective Analysis. AB - OBJECTIVE: To investigate the links between group-level affective organizational commitment (AOC) and individual-level psychological well-being, self-reported sickness absence, and sleep disturbances. METHODS: A total of 5085 care workers from 301 workgroups in the Danish eldercare services participated in both waves of the study (T1 [2005] and T2 [2006]). The three outcomes were analyzed using linear multilevel regression analysis, multilevel Poisson regression analysis, and multilevel logistic regression analysis, respectively. RESULTS: Group-level AOC (T1) significantly predicted individual-level psychological well-being, self reported sickness absence, and sleep disturbances (T2). The association between group-level AOC (T1) and psychological well-being (T2) was fully mediated by individual-level AOC (T1), and the associations between group-level AOC (T1) and self-reported sickness absence and sleep disturbances (T2) were partially mediated by individual-level AOC (T1). CONCLUSIONS: Group-level AOC is an important predictor of employee well-being in contemporary health care organizations. PMID- 26539761 TI - Employer-Based Screening for Diabetes and Prediabetes in an Integrated Health Care Delivery System: A Natural Experiment for Translation in Diabetes (NEXT-D) Study. AB - OBJECTIVE: This study evaluates an employer-based diabetes/prediabetes screening intervention that invited at-risk employees via letters, secure e-mails, and automated voice messages to complete blood glucose testing at a health plan facility. METHODS: Quasi-experimental cohort study among health plan members insured by two employers that received the intervention and three employers that were selected as control sites. RESULTS: The proportion of at-risk members that completed a screening was higher in the intervention group than in the control group (36% vs 13%, P < 0.001, adjusted for patient characteristics). Among those screened in the intervention group, the presence of obesity, hypertension, hyperlipidemia, and tobacco use were significant predictors of having a result that indicated diabetes or prediabetes (P < 0.05, all comparisons). CONCLUSIONS: A low-intensity, employer-based intervention conducted in collaboration with a health care delivery system effectively increased screening for diabetes/prediabetes. PMID- 26539762 TI - Environmental Tobacco Smoke and Atrial Fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. AB - OBJECTIVE: This study examines the association between environmental tobacco smoke (ETS) exposure and atrial fibrillation (AF). METHODS: We examined the cross sectional association between ETS exposure and AF in 12,021 participants (mean age: 65 +/- 9.9 years; 60% women; 40% blacks) from the REasons for Geographic And Racial Differences in Stroke study who self-identified as never smokers between 2003 and 2007. RESULTS: A total of 2503 (21%) participants reported ETS exposure. In a multivariate logistic regression model adjusted for sociodemographics and potential confounders, ETS exposure was significantly associated with AF (odds ratio = 1.27, 95% confidence interval = 1.08, 1.50). CONCLUSIONS: Our findings suggest that the harmful effects of ETS exposure extend to sustained arrhythmias such as AF. PMID- 26539763 TI - Impacts of Workplace Health Promotion and Wellness Programs on Health Care Utilization and Costs: Results From an Academic Workplace. AB - OBJECTIVE: This study evaluated the impacts of a long-standing workplace health promotion (HP) program on health care utilization and costs and estimated return on investment (ROI). METHODS: Analyses used a retrospective, observational cohort design based on 7 years (2005 to 2011) of health claims and HP program participation data for 3829 HP participants and 6617 controls. Inverse propensity score-weighted mixed-model regression methods were used to balance employee demographics and comorbidities by study arm. RESULTS: Mean monthly health care costs were $35 less for HP participants compared with controls, and results were robust based on sensitivity analyses. ROI was estimated to be $2.53 for every dollar spent on the HP program. CONCLUSIONS: Results support a positive impact of HP program participation with regard to reduced health care utilization and costs and a positive ROI. PMID- 26539764 TI - Economic Evaluation of a New Organizational RTW Intervention to Improve Cooperation Between Sick-Listed Employees and Their Supervisors: A Field Study. AB - OBJECTIVE: The purpose of this study is to assess the cost-effectiveness, utility, and -benefit of a new organizational return-to-work intervention to improve COoperation between Sick-listed employees and their Supervisors (COSS). METHODS: A field study with 6 months follow-up comparing COSS with common practice randomized participants aged 18 to 60, working at least 12 hours/week and absent for at least 2 weeks. Outcomes were initial return-to-work, quality adjusted life years, and productivity gains. RESULTS: After 6 months, COSS generated less costs when compared with common practice. Participants in the COSS group returned to work earlier, improvement in quality-adjusted life years were uncertain. Net benefits of COSS versus common practice yielded a productivity gain of ?395.89. CONCLUSIONS: Implementing COSS for sick-listed employees has potentials to reduce costs and improve productivity, and potentially quality of life. Longitudinal research might detect whether COSS also has the potential reaching sustainable return-to-work. PMID- 26539765 TI - Job Strain, Occupational Category, Systolic Blood Pressure, and Hypertension Prevalence: The Multi-Ethnic Study of Atherosclerosis. AB - OBJECTIVE: To assess associations of occupational categories and job characteristics with prevalent hypertension. METHODS: We analyzed 2517 Multi Ethnic Study of Atherosclerosis participants, working 20+ hours per week, in 2002 to 2004. RESULTS: Higher job decision latitude was associated with a lower prevalence of hypertension, prevalence ratio = 0.78 (95% confidence interval 0.66 to 0.91) for the top versus bottom quartile of job decision latitude. Associations, however, differed by occupation: decision latitude was associated with a higher prevalence of hypertension in health care support occupations (interaction P = 0.02). Occupation modified associations of sex with hypertension: a higher prevalence of hypertension in women (vs men) was observed in health care support and in blue-collar occupations (interaction P = 0.03). CONCLUSIONS: Lower job decision latitude is associated with hypertension prevalence in many occupations. Further research is needed to determine reasons for differential impact of decision latitude and sex on hypertension across occupations. PMID- 26539766 TI - Characteristics of Employees of Small Manufacturing Businesses by Occupation: Informing Evidence-Based Intervention Planning. AB - OBJECTIVES: We examined characteristics of employees in six occupational categories in small manufacturing businesses (20-150 employees). METHODS: We analyzed survey data from 47 businesses (n = 2577 employees; 86% response rate) and examined relationships between job type and sociodemographic, health, and organizational support characteristics. Analyses were adjusted for age and sex, and company as a random effect. RESULTS: Smoking rates were highest for production workers (33%), production managers (27%), and support staff (28%) and lowest for managers (11%) (P <0.001). Job stress was higher for production workers and support staff than managers (P < 0.0001). Managers perceived social capital (P<0.001), safety climate (P < 0.0001) and support for smoking cessation (P < 0.001) higher than production managers, production workers, and support staff. CONCLUSIONS: Differences in characteristics by occupation call for integrated interventions that target working class employees, leverage the influence of production managers, and enhance organizational support. PMID- 26539767 TI - Anatomical UV Exposure in French Outdoor Workers. AB - BACKGROUND: Solar ultraviolet has been recognized as the main causative factor for skin cancer and is currently classified as a carcinogenic agent by International Agency for Research on Cancer. METHOD: Results from a previous phone survey conducted in 2012 in France were used to assess exposure conditions to sun among outdoor workers. Satellite data were used in combination with an exposure model to assess anatomical exposure. RESULT: The yearly median exposure of the outdoor worker population is 77 kJ/m2 to 116 kJ/m2. Road workers, building workers, and gardeners are the more exposed. About 70% of the yearly dose estimate is due to the cumulative summer and spring exposures. CONCLUSIONS: This study highlights the role of individual factors in anatomical exposure and ranks the most exposed body parts and outdoor occupations. Prevention messages should put emphasis on spring exposure, which is an important contributor to the yearly dose. PMID- 26539768 TI - Factors Associated With Availability of, and Employee Participation in, Comprehensive Workplace Health Promotion in a Large and Diverse Australian Public Sector Setting: A Cross-Sectional Survey. AB - PURPOSE: The aim of this study was to explore factors associated with the perceived availability of, and reported participation in workplace health promotion activities implemented in the Tasmanian State Service, Australia. METHODS: Data from 3228 employees were collected in 2013 on sociodemographic and work characteristics, health-related behaviors, and employee-reported availability of and participation in health-related activities. Ratios of prevalence for reported availability and participation by each factor were estimated using negative binomial regression (availability) and Poisson regression (participation). RESULTS: Significant differences in availability of different activity types were found for numerous factors. Compared with the reference categories, only administrative staff or respondents reporting any leisure-time physical activity were more likely to participate, and smokers and respondents with variable work schedules or cardiometabolic conditions were less likely. CONCLUSIONS: Employees with suboptimal health-related factors were less likely to engage with activities offered through this comprehensive workplace health promotion initiative. PMID- 26539770 TI - Increased Physical Activity Leads to Improved Health-Related Quality of Life Among Employees Enrolled in a 12-Week Worksite Wellness Program. AB - OBJECTIVE: To determine the relationship between physical activity (PA) and health-related quality of life among university employees who enrolled in a worksite wellness program (WWP). METHODS: The study was an interim analysis of data collected in a WWP. The sample consisted of 64 participants who completed 12 and 26-week follow-up appointments. RESULTS: Self-reported anxiety days significantly decreased from baseline to week 12. There were positive trends in self-rated health, vitality days, and summative unhealthy days from baseline to week 26. Among those with a self-reported history of hypertension (HTN), there was an inverse correlation between PA and summative physically and mentally unhealthy days at week 12. CONCLUSIONS: Among participants in this WWP with HTN, as PA increased there was a significant decrease in summative physically and mentally unhealthy days at week 12. PMID- 26539771 TI - The Association Between Effort-Reward Imbalance and Depressive Symptoms Is Modified by Selection, Optimization, and Compensation Strategy. AB - OBJECTIVE: To examine the main and interactive effects of effort-reward imbalance (ERI) and selection, optimization, and compensation (SOC) strategy on depressive symptoms among the working population in the City of Kumning, China. METHODS: We assessed the separate and combined effects of low versus high ERI and good versus poor SOC strategy on depressive symptoms using multivariable logistic regression analyses in a population-based sample (N = 2457). RESULTS: High ERI and poor SOC were significantly associated with depressive symptoms, respectively. In employees with both high ERI and poor SOC, the odds ratio was highly elevated as compared with the reference group (low ERI and good SOC). CONCLUSIONS: If our findings are confirmed by prospective studies, health promotion programs in work settings might consider SOC as an integral part to mitigate the adverse mental health effects of ERI. PMID- 26539769 TI - The Sustainability of an Occupational Skin Cancer Prevention Program. AB - OBJECTIVE: Sustainability of prevention programs is a public health goal. METHODS: The effectiveness of Go Sun Smart, an occupational skin cancer prevention program, was evaluated 5 to 7 years out from the conclusion of a controlled randomized dissemination trial that compared an enhanced versus basic dissemination strategy at 53 ski areas enrolled in the trial. RESULTS: Employees (n = 2940) at ski areas in the enhanced condition reported fewer sunburns but did not differ from employees in the basic condition on other sun-protection measures. Significant differences for all sun-protection practices were identified at ski areas that displayed nine or more Go Sun Smart materials or a combined total of nine or more Go Sun Smart and other sun safety messages. CONCLUSIONS: Exposure to prevention messages is an important determinant of program effectiveness and potentially of program sustainability. PMID- 26539772 TI - The Approach Taken to Substance Abuse by Occupational Physicians: A Qualitative Study on Influencing Factors. AB - OBJECTIVE: Aiming to enhance occupational physicians' (OPs) practice when dealing with employee substance abuse, this study analyzes the experiences of OPs to gain insight into the factors influencing their behavior. METHODS: Semi-structured interviews were conducted and analyzed using Interpretative Phenomenological Analysis. RESULTS: OPs act differently depending on the type of drug. Their approach was mainly determined by contextual factors and by their attitudes and skills. Many OPs want to invest in health promotion. Barriers such as lack of time and focus on periodic examinations often hamper both adequate prevention and the management of workers with substance abuse. CONCLUSIONS: The approach to substance abuse by OPs could be supported by initiatives both at the individual and the collective level. A facilitating work context seems to be particularly important in their commitment to alcohol- and drug-related issues at work. PMID- 26539773 TI - Understanding the Probability of a Disability Resulting From Work-Related Injuries. AB - OBJECTIVES: To assess the conditions under which the measured risk of a workplace injury resulting in a disability changes. METHODS: Multivariate regression analysis and administrative claims data build an understanding of the factors that underlie the probability that a workplace injury results in a disability (disability probability). RESULTS: First, jointly examining injury incidence rates and disability probabilities challenges some conclusions suggested by examining the two separately. Second, some characteristics identified as risk factors for disability when studied in isolation are not risk factors. Third, risk factors are qualitatively consistent across groups of workers but quantitatively different. CONCLUSIONS: Policymakers might draw incorrect conclusions about the risk of a workplace injury becoming a disability unless the research provides a joint assessment of incidence rates and disability probabilities and a comprehensive analysis of risk factors across worker groups. PMID- 26539774 TI - Health and Occupational Outcomes Among Injured, Nonstandard Shift Workers. AB - OBJECTIVE: This study compares health and occupational outcomes following a work related injury for nonstandard and day-shift workers. METHODS: National Population Health Survey data were used to explore outcomes 2 years post-work injury. Retrospective-matched cohort analyses examined main effects and interactions of shift schedule and work injury with changes in health, shift schedule, and labor force status. Models were adjusted for respondent characteristics, baseline health status, and occupational strength requirements. RESULTS: Injured nonstandard shift workers reported lower health utility index scores, compared with uninjured and injured daytime workers and uninjured nonstandard-shift workers. No significant interactions between shift and injury were found with schedule change and leaving the labor force. CONCLUSIONS: Injured nonstandard-shift workers are as likely to remain employed as other groups, but may be vulnerable in terms of diminished health. PMID- 26539775 TI - Occupational Interstitial Lung Diseases. AB - OBJECTIVE: Evidence-based diagnostic and treatment guidelines for occupationally related interstitial lung diseases (ILDs) have been developed and are summarized herein. METHODS: Comprehensive literature reviews were conducted with article abstraction, critiquing, objective grading, and evidence table compilation. A multidisciplinary expert panel drafted evidence- and consensus-based guidance. External peer-review was incorporated. RESULTS: Recommendations for diagnosis (n = 12) and management (n = 4) of ILD were developed. Spirometric testing, chest radiographs, and high-resolution computerized tomographic scans were recommended based upon evidence. In addition to a detailed clinical history, carbon monoxide diffusion capacity, sputum sampling, exposure assessment, 6-minute walk test, and bronchoalveolar lavage were also recommended. There was no recommendation regarding chest magnetic resonance imaging due to lack of evidence. CONCLUSIONS: Recommendations for diagnosis and management of ILD are supported by quality evidence. These guidelines may be useful to help guide providers who are tasked with diagnosing and/or treating patients with occupationally related ILD. PMID- 26539777 TI - Medical Marijuana in the Workforce. PMID- 26539778 TI - Reply to Goldsmith-Medical Marijuana in the Workforce. PMID- 26539779 TI - Fatally Flawed: Samsung's Environ Consultants. PMID- 26539780 TI - Author Response to Drs Paek and Gassert. PMID- 26539781 TI - Let us regulate pharmaceuticals: here we go again. PMID- 26539782 TI - Signing off. PMID- 26539783 TI - A Submucosal Retropharyngeal Pulsatile Mass. PMID- 26539785 TI - Organizational aspects to optimize patient's ambulatory pathway. AB - PURPOSE OF REVIEW: Successful ambulatory care implementation should combine both medical and organizational features. These two components are closely interrelated. Only optimal organization, part of a quality management program, will allow us to perform safe medical procedures and provide good patient satisfaction. This review is intended to update organizational concepts that could improve ambulatory surgery center efficiency. RECENT FINDINGS: Current organizational concepts are based on the implementation of a dedicated pathway that could be divided into sequential steps, wherein the concepts of flow time and throughput should be applied. Wasted times have to be evaluated and suppressed, so patients have to spend only the minimum required time at each step. A 'forward pathway' would allow maintaining unidirectional patients' flow to avoid any blockade and to build sequential surgical program planning. These processes are easier to implement in dedicated facilities, managed by a dedicated staff, after extensive patient preoperative information, and with the use of numeric information systems. SUMMARY: Organizational feature in ambulatory surgery center is a major determinant of patient flow, activity, resource utilization, safety, and patient satisfaction. Most of these basic principles may contribute to improve the quality of care that can also be of benefit to conventional surgical activity. PMID- 26539784 TI - Sleep-Disordered Breathing in Adolescents and Younger Adults: A Representative Population-Based Survey in Chile. AB - BACKGROUND: Prevalence and potential risk contributors of sleep-disordered breathing (SDB) in adolescents and younger adults remain unclear. We hypothesized that SDB prevalence in younger Hispanic adults is higher than the limited evidence indicates. METHODS: This is a population-based study of Hispanic subjects surveyed as part of the Chilean National Health Survey database. For this study, only subjects aged 15 to 40 years were included. Sleep and demographic questionnaires were used to assess SDB prevalence and its risk factors. Anthropometric measurements were performed in each subject. Prevalence was calculated for each SDB-related symptom. A regression model was constructed to investigate demographic risk factors of SDB. RESULTS: A total of 2,147 subjects were included. Mean age (+/- SD) was 27.2 +/- 7.2 years, n = 899 (42%) were men. Habitual snoring was highly prevalent, with an average of 53.8% in men and 38.3% in women. Snoring, witnessed apneas, and daytime somnolence increased continuously with age, with an abnormal SDB questionnaire score detected in 2.5%. Reported sleep duration was 7.61 +/- 1.67 hours during weekdays and 8.27 +/- 2.11 hours during weekends. Snoring frequency was significantly higher in men than women at nearly all age groups, and an adjusted regression model (OR [95% CI]) identified male sex (2 [1.6-2.5]; P < .001) and BMI (1.08 [1.03-1.12]; P < .001) as independent risk factors for snoring. CONCLUSION: The risk of SDB is highly prevalent in younger adults, even in females, and increases with age and BMI. The high prevalence and low awareness justify active screening and treatment of SDB in this population. PMID- 26539786 TI - Which anesthetic agents for ambulatory electro-convulsive therapy? AB - PURPOSE OF REVIEW: There have been a considerable number of research articles published in the last 10 years outlining possible advances in the provision of electro-convulsive therapy (ECT) anaesthesia. This has resulted in a range of new drugs having been proposed as useful in the ECT setting. In particular, the use of adjuvant drugs that might improve outcomes to treatment has been investigated. RECENT FINDINGS: There is a high level of interest in ketamine and remifentanil as agents that may alter response in ECT anaesthesia, by reducing cognitive effects, and minimizing the dose of induction agent. The numbers of patients involved in current trials have been small, and it is not possible to give a definitive answer as to the usefulness of these drugs at this stage. SUMMARY: This review covers the major recent trials involving new and emerging treatments in ECT, and brings the reader up to date with state of knowledge of ECT anaesthesia and pharmacology. PMID- 26539787 TI - Wrong-site regional anesthesia: review and recommendations for prevention? AB - PURPOSE OF REVIEW: Wrong-site regional anesthetic procedures are considered never events. The purpose of this review is to describe the phenomenon of wrong-site regional anesthetic blocks and identify preventive strategies. RECENT FINDINGS: The incidence of wrong-site block may be as frequent as 7.5 per 10,000 procedures. Factors contributing to wrong-site block include physician distraction, patient position change, scheduling changes, inadequate documentation, poor communication, lack of surgical consent, site marking not visible, inadequate supervision, reduced situational awareness, fatigue, cognitive overload, perceived time pressure, delay from World Health sign-in to block performance and omission of block time-out or block time-out occurring before final patient positioning. The American Society of Regional Anesthesia and Pain Medicine have created a 9-point checklist for regional anesthesia procedures. SUMMARY: Preoperative site verification and surgical site marking are mandatory. A time-out should occur immediately before any invasive procedure. Confirming the correct patient and block site with a time-out should occur immediately before all regional anesthetic procedures. If more than one block is performed on one patient, it is recommended that time-out be repeated each time the patient position is changed or separated in time or performed by a different team. The anesthetic team should uniformly implement robust guidelines and checklists to reduce the occurrence of wrong-site regional anesthetic procedures. PMID- 26539788 TI - Alarm fatigue: impacts on patient safety. AB - PURPOSE OF REVIEW: Electronic medical devices are an integral part of patient care. As new devices are introduced, the number of alarms to which a healthcare professional may be exposed may be as high as 1000 alarms per shift. The US Food and Drug Administration has reported over 500 alarm-related patient deaths in five years. The Joint Commission, recognizing the clinical significance of alarm fatigue, has made clinical alarm management a National Patient Safety Goal. RECENT FINDINGS: Potential solutions to alarm fatigue include technical, organizational, and educational interventions. Selecting only the right monitors (i.e., avoiding overmonitoring), judicious selection of alarm limits, and multimodal alarms can all reduce the number of nuisance alarms to which a healthcare worker is exposed. SUMMARY: Alarm fatigue can jeopardize safety, but some clinical solutions such as setting appropriate thresholds and avoiding overmonitoring are available. PMID- 26539789 TI - The role of ultrasound guidance for vascular access. AB - PURPOSE OF REVIEW: Ultrasound-guided cannulation of the internal jugular vein has become a standard practice over recent years. Despite known benefits, ultrasound is less frequently used for other vascular applications probably because these are technically demanding and require more experience. The authors of this review focus on pitfalls of ultrasound guidance: most important practical aspects as well as nonroutine vascular applications are discussed. RECENT FINDINGS: Ultrasound guidance increases the first-pass and overall success rates and reduces the risk of complications of central venous catheterization through the subclavian and femoral routes, as well as arterial and difficult peripheral venous access. Ultrasound is also useful to detect catheter malposition and complications. Technical improvements and new modifications of old ultrasound guided techniques may result in better outcomes. SUMMARY: Growing evidence suggests that routine utilization of ultrasound guidance is beneficial for all types of vascular access. The presence of a skilled operator and proper technique are, however, required to achieve success and avoid complications. PMID- 26539790 TI - Laryngeal mask airway indications: new frontiers for second-generation supraglottic airways. AB - PURPOSE OF REVIEW: Because of the many advantages of supraglottic airways (SGA) compared to mask ventilation and endotracheal intubation, their areas of application are constantly expanding. The development of second-generation SGAs in particular has led to a widening of the indications for use thanks to the improved oropharyngeal leak pressure and the possibility of inserting a gastric tube. The identification of possible malpositions and any increased ventilation requirements using simple clinical tests must be given particular emphasis. The question of patient safety for expanded indications has to be evaluated. RECENT FINDINGS: The review describes the evolution of these devices in detail with an analysis of the increased range of possible uses for prolonged application periods, minor laparoscopic procedures, obese patients, surgery in the prone position, and caesarean sections. SUMMARY: The use of second-generation SGA for expanded indications seems useful and safe, provided the contraindications are heeded, the placement and performance tests are successfully completed and there is adequate clinical expertise. PMID- 26539792 TI - Statistical Analysis of a Method to Predict Drug-Polymer Miscibility. AB - In this study, a method proposed to predict drug-polymer miscibility from differential scanning calorimetry measurements was subjected to statistical analysis. The method is relatively fast and inexpensive and has gained popularity as a result of the increasing interest in the formulation of drugs as amorphous solid dispersions. However, it does not include a standard statistical assessment of the experimental uncertainty by means of a confidence interval. In addition, it applies a routine mathematical operation known as "transformation to linearity," which previously has been shown to be subject to a substantial bias. The statistical analysis performed in this present study revealed that the mathematical procedure associated with the method is not only biased, but also too uncertain to predict drug-polymer miscibility at room temperature. Consequently, the statistical inference based on the mathematical procedure is problematic and may foster uncritical and misguiding interpretations. From a statistical perspective, the drug-polymer miscibility prediction should instead be examined by deriving an objective function, which results in the unbiased, minimum variance properties of the least-square estimator as provided in this study. PMID- 26539793 TI - Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer. AB - IMPORTANCE: Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer. OBJECTIVE: To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years. INTERVENTIONS: Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year. MAIN OUTCOMES AND MEASURES: Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported. RESULTS: Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%. CONCLUSIONS AND RELEVANCE: Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals. PMID- 26539794 TI - Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans. AB - Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. There have however been reports in many systems of cases where restricted food intake either shortens, or does not affect, lifespan. Here we analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans. These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and also in the likelihood of maternal, matricidal, hatching. Importantly, in the wild isolates and the ILs, we identify genotypes in which peptone deprivation mediated dietary restriction reduces lifespan. We also identify, in recombinant inbred lines, a locus that affects maternal hatching, a phenotype closely linked to dietary restriction in C. elegans. These results indicate that peptone deprivation mediated dietary restriction affects lifespan in C. elegans in a genotype-dependent manner, reducing lifespan in some genotypes. This may operate by a mechanism similar to dietary restriction. PMID- 26539796 TI - WHITE ANNULAR RETINAL DYSTROPHY WITH SEVERE GLAUCOMA: A New Autosomal Dominant Condition. AB - PURPOSE: To report a family with a previously unreported characteristic retinal dystrophy and glaucoma. METHODS: Seven family members were diagnosed with an atypical retinal dystrophy and open-angle glaucoma with rapid evolution. Ophthalmic examination, fluorescein angiography, color photography, optic coherence tomography, central visual-field examination, and ultrasonography were performed. RESULTS: Of the 7 patients, 3 had 360 degrees of peripheral white retina and a broad white ring around the optic disc. In three others, it was not possible to observe the peripheral retina, but they also showed a white retinal ring around the optic disc. One patient showed posterior synechiae and iris neovascularization in one eye. The 37-year-old uncle of the proband had a probably related maculopathy. Five patients had severe glaucoma, and the youngest showed borderline intraocular pressure. CONCLUSION: The authors report a new dominant retinal dystrophy associated with open-angle glaucoma. The early onset and rapidly progressive glaucoma of the patients is atypical. PMID- 26539797 TI - Correspondence. PMID- 26539795 TI - Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations. AB - Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus and not only has catalyzed a more comprehensive understanding of neuroblastoma tumorigenesis but also has revealed novel oncogenic vulnerabilities that are being therapeutically leveraged. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog) amplification, for risk stratification. Given the relative paucity of recurrent, activating, somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed toward aberrantly regulated pathways in relapsed disease. This review summarizes the current state of knowledge about neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma. PMID- 26539798 TI - Reply: To PMID 25635574. PMID- 26539800 TI - Temporal analysis of reassortment and molecular evolution of Cucumber mosaic virus: Extra clues from its segmented genome. AB - Cucumber mosaic virus (CMV) is a damaging pathogen of over 200 mono- and dicotyledonous crop species worldwide. It has the broadest known host range of any virus, but the timescale of its evolution is unknown. To investigate the evolutionary history of this virus, we obtained the genomic sequences of 40 CMV isolates from brassicas sampled in Iran, Turkey and Japan, and combined them with published sequences. Our synonymous ('silent') site analyses revealed that the present CMV population is the progeny of a single ancestor existing 1550-2600 years ago, but that the population mostly radiated 295-545 years ago. We found that the major CMV lineages are not phylogeographically confined, but that recombination and reassortment is restricted to local populations and that no reassortant lineage is more than 251 years old. Our results highlight the different evolutionary patterns seen among viral pathogens of brassica crops across the world. PMID- 26539799 TI - Human beta-defensins 2 and -3 cointernalize with human immunodeficiency virus via heparan sulfate proteoglycans and reduce infectivity of intracellular virions in tonsil epithelial cells. AB - We previously showed that expression of the anti-HIV innate proteins human beta defensin 2 (hBD2) and hBD3 in adult oral epithelial cells reduces HIV transepithelial transmission by inactivation of virus. However, fetal/infant oral epithelia lack beta-defensin expression, leading to transmission of HIV. The mechanisms of hBD2- and hBD3-mediated HIV inactivation in adult oral epithelial cells are poorly understood. Here we found that heparan sulfate proteoglycans (HSPGs) on the apical surfaces of epithelial cells facilitate simultaneous binding of hBDs and HIV gp120 to the cell surface. HSPG-facilitated binding of hBDs and HIV gp120 to the cell surface did not affect viral attachment. HBD2 or 3 cointernalized with virions in endosomes, formed oligomers, and reduced infectivity of HIV. The anti-HIV effect of combining hBD2 and hBD3 was substantially higher than that of the individual peptides. These findings advance our understanding of the mechanisms of anti-HIV resistance in adult oral epithelium. PMID- 26539801 TI - Directing vaccine immune responses to mucosa by nanosized particulate carriers encapsulating NOD ligands. AB - Mucosal surfaces are a major portal of entry for many pathogens that are the cause of infectious diseases. Therefore, effective vaccines that induce a protective immune response at these sites are much needed. However, despite early success with the live attenuated oral polio vaccine over 50 years ago, only a few new mucosal vaccines have been subsequently licensed. Development of new adjuvants, comprising antigen delivery platforms and immunostimulatory molecules, are critical for the successful development of new mucosal vaccines. Among them, biodegradable nanoparticle delivery systems are promising and NOD-like receptors are considered as potential new targets for immunostimulatory molecules. In this work, different NOD1 and NOD2 ligands were encapsulated in polylactic acid (PLA) nanoparticles, coated with HIV-1 gag p24 antigen. We showed that these new formulations are able to induce proliferation of HIV-specific T cells from HIV(+) individuals as well as autophagy. In vivo, these formulations highly enhanced p24 specific systemic and mucosal immune responses in mice not only after mucosal administration but also after immunization via the parenteral route. Our results provide a rational approach for combining nanosized particulate carriers and encapsulated NOD receptor ligands as potent synergistic tools for induction of specific mucosal immunity. PMID- 26539802 TI - P-glycoprotein and its inducible expression in three bivalve species after exposure to Prorocentrum lima. AB - P-glycoprotein (P-gp or ABCB1) belongs to the family of ATP-binding cassette (ABC) transporters responsible for multixenobiotic resistance (MXR) in aquatic organisms. To provide more information of P-gp in shellfish, in this study, complete cDNA of P-gp in three bivalve species including Ruditapes philippinarum, Scapharca subcrenata and Tegillarca granosa were cloned and its expressions in gill, digestive gland, adductor muscle and mantle of the three bivalves were detected after exposure to Prorocentrum lima, a toxogenic dinoflagellate. The complete sequences of R. philippinarum, S. subcrenata and T. granosa P-gp showed high homology with MDR/P-gp/ABCB proteins from other species, having a typical sequence organization as full transporters from the ABCB family. Phylogenetic analyses revealed that the amino acid sequences of P-gp from S. subcrenata and T. granosa had a closest relationship, forming an independent branch, then grouping into the other branch with Mytilus californianus, Mytilus galloprovincialis and Crassostrea gigas. However, P-gp sequences from R. philippinarum were more similar to the homologs from the more distantly related Aplysia californica than to homologs from S. subcrenata and T. granosa, suggesting that bivalves P-gp might have different paralogs. P-glycoprotein expressed in all detected tissues but there were large differences between them. After exposure to P. lima, the expression of P-gp changed in the four tissues in varying degrees within the same species and between different species, but the changes in mRNA and protein level were not always synchronous. PMID- 26539803 TI - Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors. AB - Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol EE2) at 1, 10 and 50MUM; (2) an ER antagonist (ICI 182,780) at 10 and 50MUM; and (3) mixtures of both (Mix I-10MUM EE2 and 50MUM ICI; Mix II-1MUM EE2 and 10MUM ICI and Mix III-1MUM EE2 and 50MUM ICI). The mRNA levels of the estrogenic targets (ERalpha, ERbeta-1 and vitellogenin A-VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase-Uox, 17beta hydroxysteroid dehydrogenase 4-17beta-HSD4, peroxin 11alpha-Pex11alpha and PPARalpha) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50MUM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERalpha mRNA increased after all EE2 treatments, while ERbeta-1 had an inverse pattern. The EE2 action was reversed by ICI 182,780 in a concentration-dependent manner, for VtgA, ERalpha and Uox. Overall, our data show the great value of primary brown trout hepatocytes to study the effects of estrogenic/anti-estrogenic inputs in peroxisome kinetics and in ER and PPARalpha signaling, backing the still open hypothesis of crosstalk interactions between these pathways and calling for more mechanistic experiments. PMID- 26539804 TI - Poisson's ratio of arterial wall - Inconsistency of constitutive models with experimental data. AB - Poisson's ratio of fibrous soft tissues is analyzed in this paper on the basis of constitutive models and experimental data. Three different up-to-date constitutive models accounting for the dispersion of fibre orientations are analyzed. Their predictions of the anisotropic Poisson's ratios are investigated under finite strain conditions together with the effects of specific orientation distribution functions and of other parameters. The applied constitutive models predict the tendency to lower (or even negative) out-of-plane Poisson's ratio. New experimental data of porcine arterial layer under uniaxial tension in orthogonal directions are also presented and compared with the theoretical predictions and other literature data. The results point out the typical features of recent constitutive models with fibres concentrated in circumferential-axial plane of arterial layers and their potential inconsistence with some experimental data. The volumetric (in)compressibility of arterial tissues is also discussed as an eventual and significant factor influencing this inconsistency. PMID- 26539805 TI - Circulating levels of adipocytokine omentin-1 in patients with renal cell cancer. AB - Renal cell carcinoma (RCC) is the fifth most common cancer worldwide, and becomes one of the leading causes of genitourinary cancer-related death in both males and females. Genetic alternations, alcohol consumption, occupationally harmful exposure and even obesity are well-established risk factors of RCC. Omentin-1 is a plasma adipokine synthesized in visceral adipose tissue, and its circulating serum concentration alters not only in conditions associated with insulin resistance such as Polycystic Ovary Syndrome (PCOS), but also in colorectal cancer and prostate cancer. To our best knowledge, the relationship between omentin-1 and RCC has not been clarified previously. Thus, we evaluated serum omentin-1 levels in RCC patients in the current matched case-control study. Forty one patients newly diagnosed with RCC and forty-two healthy controls confirmed by the comprehensive medical examination were assessed. The omentin-1 concentrations were determined via utilizing enzyme-linked immunosorbent assays (ELISA) in the paired groups, in which the patients and healthy controls had no statistically significant differences in gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), estimate glomerular filtration rate (eGFR), body-mass index (BMI) and biochemical parameters. The omentin-1 levels in healthy people were 9.86+/-1.44ng/mL and the circulating omentin-1 levels were dramatically decreased to 3.62+/-0.76ng/mL in RCC patients (p<0.001). Besides, we revealed a negative correlation between omentin-1 with WHR (r=-0.261, p=0.017) and BMI (r=-0.310, p=0.004), further indicating BMI was the main influential factor on omentin-1 levels (p=0.0091). Follow-up studies would be conducted to establish the concrete mechanisms underlying the altered circulating levels of omentin-1 and elucidate the interaction between "RCC complex system" and adipose tissues, which may together provide promising and novel pharmacological insights for RCC theragnosis in the near future. PMID- 26539807 TI - Insertion of pH-sensitive bola-type copolymer into liposome as a "stability anchor" for control of drug release. AB - How to design intelligent carriers for delivering drugs to the target accurately and releasing drug timely with the help of a certain environmental stimulus is still a challenge in tumor treatment. In this work, pH-sensitive bola-type triblock copolymers, composed of poly(2-(diisopropylamino) ethylmethacrylate) (PDPA) and methoxy-poly(ethyleneglycol) (mPEG), were synthesized. Liposomes containing these copolymers (Liposome@Bola) have been prepared by simply mixing the copolymer with phospholipids and cholesterol. From the fluorescence polarization measurement, the stability of Liposome@Bola was found to be increased a lot comparing to the pure liposome. As a result, the doxorubicin (DOX) leakage of the former was restrained in neutral environment. However, when pH decreased from 7.4 to 6.0, DOX released percentage had been increased 30-60 points, which was heavily depend on the phospholipid composition. Furthermore, the size effects of PEG and PDPA segments were also investigated. These results indicated the synthesized bola-type copolymers improved the pH-controllability of drug release of liposome, i.e., increased the difference between the release amount under pH 7.4 and pH 6.0. The bola-type copolymer exhibited a good potential application in smartly controlling drug delivery system. PMID- 26539806 TI - Variation in blood levels of hormones in obese patients following weight reduction induced by endoscopic and surgical bariatric therapies. AB - BACKGROUND: Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. METHODS: Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. RESULTS: Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non obese. At 50-54weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50-54weeks after therapy. CONCLUSION: Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies. PMID- 26539808 TI - Incorporation of lapatinib into human serum albumin nanoparticles with enhanced anti-tumor effects in HER2-positive breast cancer. AB - Lapatinib, a selective small-molecule dual-tyrosine kinase inhibitor of HER2 and EGFR, is effective in HER2-positive patients with advanced metastatic breast cancer. However, its low and variable oral absorption, large required daily dose and serious gastrointestinal side effects all limit its clinical use. Intravenous administration offers a good option to overcome these disadvantages. However, the poor solubility of lapatinib in water and organic solvents causes lapatinib to fail in a common injectable preparation. Considering lapatinib's high albumin binding ability (>99%), in this study, we developed human serum albumin nanoparticles loaded with lapatinib (LHNPs) by Nab technology for intravenous administration and investigated its efficacy against HER2-positive breast cancer. Raman shift, X-ray diffraction and X-ray photoelectron spectroscopy studies demonstrated that lapatinib was successfully incorporated into nanoparticles, and LHNPs exhibited good stability and sustained-release effect in vitro. LHNPs could be effectively taken up by SKBr3 cells in a concentration- and time-dependent manner, and the uptake was mediated by energy-dependent endocytosis, which involved clathrin-dependent pinocytosis. Furthermore, in vitro and in vivo data indicated that LHNPs presented the strong ability to induce apoptosis and superior anti-tumor efficacy in tumor-bearing mice to the commercial tablet Tykerb through the inhibition of HER2 phosphorylation. Subchronic toxicity assays indicated that LHNPs had no hepatic or kidney toxicity. With mature technology for industrial production and enhanced therapeutic effects, LHNPs are likely to have great potential as a safe therapeutic candidate against HER2-positive breast cancer in the clinic. PMID- 26539809 TI - Ultrafast laser functionalized rare phased gold-silicon/silicon oxide nanostructured hybrid biomaterials. AB - We introduce a hybrid nanostructured biomaterial that is a combination of rare phases of immiscible gold and silicon oxide, functionalized via ultrafast laser synthesis. For the first time, we show cancer controlling properties of rare phases of gold silicides, which include Au7Si, Au5Si, Au0.7Si2.3 and Au8Si2. Conventionally, pure forms of gold and silicon/silicon oxide are extensively employed in targeted therapy and drug delivery systems due to their unique properties. While silicon and silicon oxide nanoparticles have shown biocompatibility, gold nanoparticles show conflicting results based on their size and material properties. Several studies have shown that gold and silicon combinations produce cell controlling properties, however, these studies were not able to produce a homogenous combination of gold and silicon, owing to its immiscibility. A homogenous combination of gold and silicon may potentially enable properties that have not previously been reported. We describe rare phased gold-silicon oxide nanostructured hybrid biomaterials and its unique cancer controlling properties, owing to material properties, concentration, size and density. The gold-silicon oxide nanostructured hybrid is composed of individual gold-silicon oxide nanoparticles in various concentrations of gold and silicon, some nanoparticles possess a gold-core and silicon-shell like structure. The individual nanoparticles are bonded together forming a three dimensional nanostructured hybrid. The interaction of the nanostructured hybrids with cervical cancer cells showed a 96% reduction in 24h. This engineered nanostructured hybrid biomaterial presents significant potential due to the combination of immiscible gold and silicon oxide in varying phases and can potentially satiate the current vacuum in cancer therapy. PMID- 26539810 TI - A facile magnesium-containing calcium carbonate biomaterial as potential bone graft. AB - The calcium carbonate is the main composition of coral which has been widely used as bone graft in clinic. Herein, we readily prepared novel magnesium-containing calcium carbonate biomaterials (MCCs) under the low-temperature conditions based on the dissolution-recrystallization reaction between unstable amorphous calcium carbonate (ACC) and metastable vaterite-type calcium carbonate with water involved. The content of magnesium in MCCs was tailored by adjusting the proportion of ACC starting material that was prepared using magnesium as stabilizer. The phase composition of MCCs with various amounts of magnesium was composed of one, two or three kinds of calcium carbonates (calcite, aragonite, and/or magnesian calcite). The different MCCs differed in topography. The in vitro degradation of MCCs accelerated with increasing amount of introduced magnesium. The MCCs with a certain amount of magnesium not only acquired higher compressive strength, but also promoted in vitro cell proliferation and osteogenic differentiation. Taken together, the facile MCCs shed light on their potential as bone graft. PMID- 26539811 TI - A biomemory chip composed of a myoglobin/CNT heterolayer fabricated by the protein-adsorption-precipitation-crosslinking (PAPC) technique. AB - In this study, a biomemory chip consisting of a myoglobin/carbon nanotube (CNT) heterolayer is fabricated via the protein-adsorption-precipitation-crosslinking (PAPC) technique for electrochemical signal enhancement, long-term stability, and improved memory function. The PAPC technique is used to fabricate a myoglobin/CNT heterolayer with a CNT core and a high-density myoglobin-shell structure to achieve efficient heterolayer formation and improved performance of the heterolayer. The fabricated myoglobin/CNT heterolayer is immobilized onto a Au substrate through a chemical linker. The surface morphology of the deposited heterolayer is investigated via transmission electron microscopy and atomic force microscopy. The redox properties of the myoglobin/CNT heterolayer are investigated by cyclic voltammetry, and the memory function of the heterolayer, including the "write step" and "erase step," is measured by chronoamperometry. Compared with the myoglobin monolayer without CNT, the myoglobin/CNT heterolayer fabricated by the PAPC technique exhibits greater electrochemical signal enhancement, long-term stability at room temperature, and improved memory function. The results suggest that the proposed myoglobin/CNT heterolayer produced via the PAPC technique can be applied as a platform for bioelectronic devices to achieve improved signal intensity and durability. PMID- 26539812 TI - Short-lived positron emitters in beam-on PET imaging during proton therapy. AB - The only method for in vivo dose delivery verification in proton beam radiotherapy in clinical use today is positron emission tomography (PET) of the positron emitters produced in the patient during irradiation. PET imaging while the beam is on (so called beam-on PET) is an attractive option, providing the largest number of counts, the least biological washout and the fastest feedback. In this implementation, all nuclides, independent of their half-life, will contribute. As a first step towards assessing the relevance of short-lived nuclides (half-life shorter than that of (10)C, T1/2 = 19 s) for in vivo dose delivery verification using beam-on PET, we measured their production in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: (12)N (T1/2 = 11 ms) on carbon (9% of (11)C), (29)P (T1/2 = 4.1 s) on phosphorus (20% of (30)P) and (38m)K (T1/2 = 0.92 s) on calcium (113% of (38g)K). No short-lived nuclides are produced on oxygen. The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, (12)N dominates up to 70 s. On bone tissue, (12)N dominates over (15)O during the first 8-15 s (depending on carbon to-oxygen ratio). The short-lived nuclides created on phosphorus and calcium provide 2.5 times more beam-on PET counts than the long-lived ones produced on these elements during a 70 s irradiation. From the estimated number of (12)N PET counts, we conclude that, for any tissue, (12)N PET imaging potentially provides equal to superior proton range information compared to prompt gamma imaging with an optimized knife-edge slit camera. The practical implementation of (12)N PET imaging is discussed. PMID- 26539814 TI - Mechanically Durable and Biologically Favorable Protein Hydrogel Based on Elastic Silklike Protein Derived from Sea Anemone. AB - As biodegradable scaffolds, protein hydrogels have considerable potential, particularly for bioartificial organs and three-dimensional space-filling materials. However, their low strength and stiffness have been considered to be limitations for enduring physiological stimuli. Therefore, protein hydrogels have been commonly utilized as delivery vehicles rather than as supporting materials. In this work, sea anemone tentacle-derived recombinant silk-like protein (aneroin) was evaluated as a potential material for a mechanically durable protein hydrogel. Inspired by the natural hardening mechanism, photoinitiated dityrosine cross-linking was employed to fabricate an aneroin hydrogel. It was determined that the fabricated aneroin hydrogel was approximately 10-fold stiffer than mammalian cardiac or skeletal muscle. The aneroin hydrogel provided not only structural support but also an adequate environment for cells. It exhibited an adequate swelling ability and microstructure, which are beneficial for facilitating mass transport and cell proliferation. Based on its mechanical and biological properties, this aneroin hydrogel could be used in various biomedical applications, such as cell-containing patches, biomolecule carriers, and artificial extracellular matrices. PMID- 26539813 TI - Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders. AB - This study examined the short- and long-term neuroprotective and analgesic activity of honokiol (a naturally occurring lignan isolated from Magnolia) on developing brains in neonates exposed to inflammatory pain, known to cause neuronal cell death. Postnatal day 4 (P4) neonatal rat pups were subjected to intraplantar formalin injection to four paws as a model of severe neonatal pain. Intraperitoneal honokiol (10 mg/kg) or corn oil vehicle control was administered 1 h prior to formalin insult, and animals were maintained on honokiol through postnatal day 21 (P21). Behavioral tests for stress and pain were performed after the painful insult, followed by morphological examinations of the brain sections at P7 and P21. Honokiol significantly attenuated acute pain responses 30 min following formalin insult and decreased chronic thermal hyperalgesia later in life. Honokiol-treated rats performed better on tests of exploratory behavior and performed significantly better in tests of memory. Honokiol treatment normalized hippocampal and thalamic c-Fos and hippocampal alveus substance P receptor expression relative to controls at P21. Together, these findings support that (1) neonatal pain experiences predispose rats to the development of chronic behavioral changes and (2) honokiol prevents and reduces both acute and chronic pathological pain-induced deteriorations in neonatal rats. PMID- 26539815 TI - Simultaneous infrared detection of the ICH2OO radical and Criegee intermediate CH2OO: the pressure dependence of the yield of CH2OO in the reaction CH2I + O2. AB - The simplest Criegee intermediate CH2OO, important in atmospheric reactions, has been recently produced from the reaction of CH2I + O2 and detected with various methods. In this reaction, the yield of CH2OO decreases with increasing pressure because of the stabilization of the adduct ICH2OO, but no definitive spectral identification of ICH2OO has been reported. We recorded the infrared spectrum of ICH2OO using the same reaction under high pressure; the spectrum agrees with that simulated according to theoretical predictions. With direct detection of both CH2OO and ICH2OO, we determined the pressure dependence of the yield of CH2OO. The yield of CH2OO near 1 atm is greater than previously reported values, which might have significant consequences in atmospheric chemistry. PMID- 26539818 TI - Searching for Clever Life. PMID- 26539816 TI - Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. AB - AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery. METHODS: PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency). RESULTS: In the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD. PMID- 26539819 TI - Species Differences in the Geometry of the Anterior Segment Differentially Affect Anterior Chamber Cell Scoring Systems in Laboratory Animals. AB - PURPOSE: To determine the impact of anterior segment geometry on ocular scoring systems quantifying anterior chamber (AC) cells in humans and 7 common laboratory species. METHODS: Using normative anterior segment dimensions and novel geometric formulae, ocular section volumes measured by 3 scoring systems; Standardization of Uveitis Nomenclature (SUN), Ocular Services On Demand (OSOD), and OSOD modified SUN were calculated for each species, respectively. Calculated volumes were applied to each system's AC cell scoring scheme to determine comparative cell density (cells/mm(3)). Cell density values for all laboratory species were normalized to human values and conversion factors derived to create modified scoring schemes, facilitating interspecies comparison with each system, respectively. RESULTS: Differences in anterior segment geometry resulted in marked differences in optical section volume measured. Volumes were smaller in rodents than dogs and cats, but represented a comparatively larger percentage of AC volume. AC cell density (cells/mm(3)) varied between species. Using the SUN and OSOD-modified SUN systems, values in the pig, dog, and cat underestimated human values; values in rodents overestimated human values. Modified normalized scoring systems presented here account for species-related anterior segment geometry and facilitate both intra- and interspecies analysis, as well as translational comparison. CONCLUSIONS: Employment of modified AC cell scoring systems that account for species-specific differences in anterior segment anatomy would harmonize findings across species and may be more predictive for determining ocular toxicological consequences in ocular drug and device development programs. PMID- 26539820 TI - Heartwood extract of Rhus verniciflua Stokes and its active constituent fisetin attenuate vasoconstriction through calcium-dependent mechanism in rat aorta. AB - Rhus verniciflua Stokes (RVS) exert cardiovascular protective activity by promoting blood circulation, but its active ingredients and underlying mechanism have yet to be identified. This study investigated the vascular effects of RVS, focusing on vasoconstriction and smooth muscle Ca(2+) signaling. RVS heartwood extract attenuated contraction of aortic rings induced by the vasoconstrictors serotonin and phenylephrine, and inhibited the Ca(2+) signaling evoked by serotonin in vascular smooth muscle cells. Subsequent activity-guided fractionation identified fisetin as an active constituent exerting a Ca(2+) inhibitory effect. Fisetin could inhibit major Ca(2+) mobilization pathways including extracellular Ca(2+) influx mediated by the L-type voltage-gated Ca(2+) channel, Ca(2+) release from the intracellular store and store-operated Ca(2+) entry. In accordance with Ca(2+) inhibitory effect, fisetin attenuated vasoconstriction by serotonin and phenylephrine. These results suggest that the anticontractile effect, which is presumably mediated by inhibition of Ca(2+) signaling, may contribute to the improvement of blood circulation by RVS. PMID- 26539821 TI - Multiple Origins of Mutations in the mdr1 Gene--A Putative Marker of Chloroquine Resistance in P. vivax. AB - BACKGROUND: Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. OBJECTIVE: In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. METHODS: We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, Sao Tome and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. RESULTS: SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00-0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic sites which could indicate directional selection through local drug pressure. CONCLUSIONS: Our observations suggest that Pvmdr1 mutations emerged independently on multiple occasions even within the same population. In Sri Lanka population analysis at multiple sites showed evidence of local selection and geographical dispersal of Pvmdr1 mutations between sites. PMID- 26539822 TI - Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection. AB - Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNgamma responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naive mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID- 26539823 TI - Reversal of Endothelial Dysfunction by GPBAR1 Agonism in Portal Hypertension Involves a AKT/FOXOA1 Dependent Regulation of H2S Generation and Endothelin-1. AB - BACKGROUND: GPBAR1 is a bile acids activated receptor expressed in entero-hepatic tissues. In the liver expression of GPBAR1 is restricted to sinusoidal and Kuppfer cells. In the systemic circulation vasodilation caused by GPBAR1 agonists is abrogated by inhibition of cystathione-gamma-liase (CSE), an enzyme essential to the generation of hydrogen sulfide (H2S), a vasodilatory agent. Portal BAR501 is a semisynthetic bile acid derivative endowed with a potent and selective agonistic activity toward GPBAR1. METHODS: Cirrhosis was induced in mice by carbon tetrachloride (CCL4) administration for 9 weeks. Liver endothelial dysfunction was induced by feeding wild type and Gpbar1-/- mice with methionine for 4 weeks. In both models, mice were administered BAR501, 15 mg/kg/day. RESULTS: By transactivation assay we demonstrate that BAR501 is a selective GPBAR1 agonist devoid of any FXR agonistic activity. In naive rats, BAR501 effectively reduced hepatic perfusion pressure and counteracted the vasoconstriction activity of norepinephrine. In the CCl4 model, 9 weeks treatment with BAR501 effectively protected against development of endothelial dysfunction by increasing liver CSE expression and activity and by reducing endothelin (ET)-1 gene expression. In mice feed methionine, treatment with BAR501 attenuated endothelial dysfunction and caused a GPBAR1-dependent regulation of CSE. Using human liver sinusoidal cells, we found that modulation of CSE expression/activity is mediated by both genomic (recruitment of CREB to CRE in the CSE promoter) and non-genomic effects, involving a Akt-dependent phosporylation of CSE and endothelial nitric oxide (NO) synthase (eNOS). BAR501, phosphorylates FOXO1 and inhibits ET-1 transcription in liver sinusoidal cells. CONCLUSIONS: BAR501, a UDCA-like GPBAR1 agonist, rescues from endothelial dysfunction in rodent models of portal hypertension by exerting genomic and non-genomic effects on CSE, eNOS and ET-1 in liver sinusoidal cells. PMID- 26539824 TI - Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet. AB - Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-alpha and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4 mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway. PMID- 26539825 TI - Constitutive Stringent Response Restores Viability of Bacillus subtilis Lacking Structural Maintenance of Chromosome Protein. AB - Bacillus subtilis mutants lacking the SMC-ScpAB complex are severely impaired for chromosome condensation and partitioning, DNA repair, and cells are not viable under standard laboratory conditions. We isolated suppressor mutations that restored the capacity of a smc deletion mutant (Deltasmc) to grow under standard conditions. These suppressor mutations reduced chromosome segregation defects and abrogated hypersensitivity to gyrase inhibitors of Deltasmc. Three suppressor mutations were mapped in genes involved in tRNA aminoacylation and maturation pathways. A transcriptomic survey of isolated suppressor mutations pointed to a potential link between suppression of Deltasmc and induction of the stringent response. This link was confirmed by (p)ppGpp quantification which indicated a constitutive induction of the stringent response in multiple suppressor strains. Furthermore, sublethal concentrations of arginine hydroxamate (RHX), a potent inducer of stringent response, restored growth of Deltasmc under non permissive conditions. We showed that production of (p)ppGpp alone was sufficient to suppress the thermosensitivity exhibited by the Deltasmc mutant. Our findings shed new light on the coordination between chromosome dynamics mediated by SMC ScpAB and other cellular processes during rapid bacterial growth. PMID- 26539826 TI - Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin. AB - Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin. PMID- 26539827 TI - A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma. AB - We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma. Data are available via ProteomeXchange with identifier PXD002622. PMID- 26539828 TI - Characterization of Piperacillin/Tazobactam-Resistant Klebsiella oxytoca Recovered from a Nosocomial Outbreak. AB - We characterized 12 clinical isolates of Klebsiella oxytoca with the extended spectrum beta-lactamase (ESBL) phenotype (high minimum inhibitory concentration [MIC] values of ceftriaxone) recovered over 9 months at a university hospital in Japan. To determine the clonality of the isolates, we used pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and PCR analyses to detect blaRBI, which encodes the beta-lactamase RbiA, OXY-2-4 with overproduce type promoter. Moreover, we performed the isoelectric focusing (IEF) of beta lactamases, and the determination of the MICs of beta-lactams including piperacillin/tazobactam for 12 clinical isolates and E. coli HB101 with pKOB23, which contains blaRBI, by the agar dilution method. Finally, we performed the initial screening and phenotypic confirmatory tests for ESBLs. Each of the 12 clinical isolates had an identical PFGE pulsotype and MLST sequence type (ST9). All 12 clinical isolates harbored identical blaRBI. The IEF revealed that the clinical isolate produced only one beta-lactamase. E. coli HB101 (pKOB23) and all 12 isolates demonstrated equally resistance to piperacillin/tazobactam (MICs, >128 MUg/ml). The phenotypic confirmatory test after the initial screening test for ESBLs can discriminate beta-lactamase RbiA-producing K. oxytoca from beta lactamase CTX-M-producing K. oxytoca. Twelve clinical isolates of K. oxytoca, which were recovered from an outbreak at one university hospital, had identical genotypes and produced beta-lactamase RbiA that conferred resistance to piperacillin/tazobactam. In order to detect K. oxytoca isolates that produce RbiA to promote research concerning beta-lactamase RbiA-producing K. oxytoca, the phenotypic confirmatory test after the initial screening test for ESBLs would be useful. PMID- 26539829 TI - A Mutual Self- and Informant-Report of Cognitive Complaint Correlates with Neuropathological Outcomes in Mild Cognitive Impairment. AB - BACKGROUND: This study examines whether different sources of cognitive complaint (i.e., self and informant) predict Alzheimer's disease (AD) neuropathology in elders with mild cognitive impairment (MCI). METHODS: Data were drawn from the National Alzheimer's Coordinating Center Uniform and Neuropathology Datasets (observational studies) for participants with a clinical diagnosis of MCI and postmortem examination (n = 1843, 74+/-8 years, 52% female). Cognitive complaint (0.9+/-0.5 years prior to autopsy) was classified into four mutually exclusive groups: no complaint, self-only, informant-only, or mutual (both self and informant) complaint. Postmortem neuropathological outcomes included amyloid plaques and neurofibrillary tangles. Proportional odds regression related complaint to neuropathology, adjusting for age, sex, race, education, depressed mood, cognition, APOE4 status, and last clinical visit to death interval. RESULTS: Mutual complaint related to increased likelihood of meeting NIA/Reagan Institute (OR = 6.58, p = 0.004) and Consortium to Establish a Registry for Alzheimer's Disease criteria (OR = 5.82, p = 0.03), and increased neurofibrillary tangles (OR = 3.70, p = 0.03), neuritic plaques (OR = 3.52, p = 0.03), and diffuse plaques (OR = 4.35, p = 0.02). Informant-only and self-only complaint was not associated with any neuropathological outcome (all p-values>0.12). CONCLUSIONS: In MCI, mutual cognitive complaint relates to AD pathology whereas self-only or informant-only complaint shows no relation to pathology. Findings support cognitive complaint as a marker of unhealthy brain aging and highlight the importance of obtaining informant corroboration to increase confidence of underlying pathological processes. PMID- 26539830 TI - Correlation between Quadriceps Endurance and Adduction Moment in Medial Knee Osteoarthritis. AB - It is not clear whether the strength or endurance of thigh muscles (quadriceps and hamstring) is positively or negatively correlated with the adduction moment of osteoarthritic knees. This study therefore assessed the relationships between the strength and endurance of the quadriceps and hamstring muscles and adduction moment in osteoarthritic knees and evaluated predictors of the adduction moment. The study cohort comprised 35 patients with unilateral medial osteoarthritis and varus deformity who were candidates for open wedge osteotomy. The maximal torque (60 degrees /sec) and total work (180 degrees /sec) of the quadriceps and hamstring muscles and knee adduction moment were evaluated using an isokinetic testing device and gait analysis system. The total work of the quadriceps (r = 0.429, P = 0.037) and hamstring (r = 0.426, P = 0.045) muscles at 180 degrees /sec each correlated with knee adduction moment. Preoperative varus deformity was positively correlated with adduction moment (r = 0.421, P = 0.041). Multiple linear regression analysis showed that quadriceps endurance at 180 degrees /sec was the only factor independently associated with adduction moment (beta = 0.790, P = 0.032). The adduction moment of osteoarthritic knees correlated with the endurance, but not the strength, of the quadriceps muscle. However, knee adduction moment did not correlate with the strength or endurance of the hamstring muscle. PMID- 26539831 TI - Evaluation of Antimicrobial Therapy of Blood Culture Positive Healthcare Associated Infections in Children. AB - AIM: Knowledge of the quality of antimicrobial therapy (AMT) used for invasive healthcare-associated infections (HAIs) in paediatrics is scarce. Influence of the final information about the isolated pathogen on the subsequent targeted AMT was investigated in our study. METHODS: Data on 149 children (0-17 years) with blood culture positive HAIs were collected. The causative microbes under investigation were Staphylococcus aureus, Staphylococcus epidermidis, streptococci, Gram negative rods, and mixed infections were likewise included. For adjusting the antimicrobial regimen, an expert panel evaluated the quality of the targeted AMT and the delay of 72 hours after final microbiology results. AMT was regarded as inappropriate if the pathogen was totally resistant to the used antimicrobials (i) or if the chosen therapy was of not optimal efficacy against the pathogen (ii). RESULTS: 17% of the patients received inappropriate AMT. Half of these infections 13/26 (50%) were treated with an antimicrobial to which the isolate was resistant. Three (3/13, 23%) of these patients received antimicrobials which were totally ineffective according to in vitro data. Suboptimal or too broad spectrum AMT was administered to 13/26 (50%) patients. The most common causes of inappropriate use were the use of beta-lactams in oxacillin-resistant Staphylococcus epidermidis infections and vancomycin given in oxacillin-sensitive Staphylococcus aureus infections. CONCLUSION: Approximately 17% of the selected cohort received inappropriate AMT. More attention should be paid to the appropriate use of antimicrobials, and training of prescribers should be urgently provided. PMID- 26539832 TI - Molecular Subtype-Specific Expression of MicroRNA-29c in Breast Cancer Is Associated with CpG Dinucleotide Methylation of the Promoter. AB - Basal-like breast cancer is a molecularly distinct subtype of breast cancer that is highly aggressive and has a poor prognosis. MicroRNA-29c (miR-29c) has been shown to be significantly down-regulated in basal-like breast tumors and to be involved in cell invasion and sensitivity to chemotherapy. However, little is known about the genetic and regulatory factors contributing to the altered expression of miR-29c in basal-like breast cancer. We here report that epigenetic modifications at the miR-29c promoter, rather than copy number variation of the gene, may drive the lower expression of miR-29c in basal-like breast cancer. Bisulfite sequencing of CpG sites in the miR-29c promoter region showed higher methylation in basal-like breast cancer cell lines compared to luminal subtype cells with a significant inverse correlation between expression and methylation of miR-29c. Analysis of primary breast tumors using The Cancer Genome Atlas (TCGA) dataset confirmed significantly higher levels of methylation of the promoter in basal-like breast tumors compared to all other subtypes. Furthermore, inhibition of CpG methylation with 5-aza-CdR increases miR-29c expression in basal-like breast cancer cells. Flourescent In Situ Hybridization (FISH) revealed chromosomal abnormalities at miR-29c loci in breast cancer cell lines, but with no correlation between copy number variation and expression of miR-29c. Our data demonstrated that dysregulation of miR-29c in basal-like breast cancer cells may be in part driven by methylation at CpG sites. Epigenetic control of the miR-29c promoter by epigenetic modifiers may provide a potential therapeutic target to overcome the aggressive behavior of these cancers. PMID- 26539833 TI - Evaluation of a Bacillus direct-fed microbial candidate on digesta viscosity, bacterial translocation, microbiota composition and bone mineralisation in broiler chickens fed on a rye-based diet. AB - 1. The effects of the dietary inclusion of a Bacillus-based direct-fed microbial (DFM) candidate on digesta viscosity, bacterial translocation, microbiota composition and bone mineralisation were evaluated in broilers consuming rye based diets. 2. In the present study, control mash rye-based diets (CON) or Bacillus-DFM supplemented diets (TRT) were administered ad libitum to male broilers in three independent experiments. 3. In Experiments 1 and 2 (n = 25/group), liver samples were taken to evaluate bacterial translocation, digesta samples were used for viscosity measurements and the intestinal microbial flora was evaluated from different intestinal sections to enumerate total recovered gram-negative bacteria (TGB), lactic acid bacteria (LAB) and anaerobic bacteria (TAB). Additionally, both tibias were removed for assessment of bone quality. 4. In Experiment 3, each experimental group had 8 replicates of 20 chickens (n = 160/group). Weekly, body weight (BW), feed intake (FI) and feed conversion ratio (FCR) were evaluated. At d 28-of-age, samples were taken to determine bacterial translocation, digesta viscosity and bone quality characteristics. 5. In all experiments, consumption of Bacillus-DFM reduced bacterial translocation to the liver and digesta viscosity. Additionally, DFM supplementation improved BW, bone quality measurements and FCR. Moreover, chickens fed on the Bacillus-DFM diet in Experiments 1 and 2 showed a significant reduction in the number of gram-negative and anaerobic bacteria in the duodenal content compared to control. 6. In summary, chickens fed on a rye-based diet without DFM inclusion showed an increase in bacterial translocation and digesta viscosity, accompanied by reduced performance and bone quality variables relative to the Bacillus-DFM candidate group. Hence, incorporation into the feed of a selected DFM ameliorated the adverse anti-nutritional effects related to utilisation of rye-based diets in broilers chickens. PMID- 26539834 TI - Erectile function after radical prostatectomy: Do patients return to baseline? AB - OBJECTIVE: The aim of this study was to assess postprostatectomy erectile function compared to preoperative status by subjective patient perception and the abbreviated International Index of Erectile Function (IIEF-5) questionnaire. MATERIALS AND METHODS: The study used data from a prospectively collected database and a cross-sectional, questionnaire-based study in patients following radical prostatectomy. Erectile function was assessed with the IIEF-5 and the question "Is your erectile function as good as before the surgery (yes/no)". Patients were included if they were sexually active before surgery and had at least 1 year of follow-up. The main outcome measure was the proportion of patients returning to self-perceived baseline erectile function. Secondary outcome measures included the proportion of patients returning to baseline erectile function according to the IIEF-5 and predictors of return to baseline function. RESULTS: Questionnaires from 210 patients were available. Overall, 14 patients (6.7%) reported that their erections were as good as before surgery. Bilateral nerve-sparing was the only significant predictor of a return to baseline erectile function (p = 0.004). Forty-three patients (20.5%), who did not report use of erectile aids, showed no decline in IIEF-5 score. When including patients who used erectogenic aids, 69 (32.9%) maintained their preoperative IIEF 5 score. On multivariate analysis a low preoperative IIEF-5 score was a significant predictor of return to baseline IIEF-5 score (p < 0.0001). CONCLUSIONS: Return to subjective baseline erectile function following radical prostatectomy is rare. The IIEF-5 questionnaire may not adequately reflect patients' experience. This should be considered in preoperative patient counselling. PMID- 26539836 TI - Lidocaine Skin Patch (Lidopat(r) 5%) Is Effective in the Treatment of Traumatic Rib Fractures: A Prospective Double-Blinded and Vehicle-Controlled Study. AB - OBJECTIVE: The purpose of this study was to determine the efficacy of the Lidopat((r)) 5% skin patch in relieving rib fracture pain. SUBJECTS AND METHODS: From June 2009 to May 2011, 44 trauma patients with isolated rib fractures were enrolled in this study and randomized in a double-blind method into 2 groups. The experimental group (group E: 27 patients) used a Lidopat((r)) 5% skin patch at the trauma site and took an oral analgesic drug for pain relief. The placebo group (group P: 17 patients) used a placebo vehicle patch and an oral analgesic drug. RESULTS: The mean age, weight and hospital stay of patients were 56.8 +/- 13.8 years, 67.4 +/- 12.6 kg and 6.34 +/- 1.3 days, respectively. In the first 4 days, there were no significant differences in pain scores between the groups (p > 0.05). After the 5th day, the average pain score was significantly less in group E (mean 1.5) than in group P (mean 3.10; p < 0.05). There was no significant difference in the number of fractured ribs between groups (p = 0.904). The use of meperidine and the length of hospital stay (6.0 vs. 6.9 days) were both significantly less in group E (p = 0.043 and 0.009, respectively). CONCLUSION: In this study, the use of the Lidopat((r)) 5% skin patch in patients with isolated rib fractures alleviated pain and shortened the hospital stay, and a lower dose of pain-relieving medication was used. PMID- 26539835 TI - Soluble Urokinase Receptor and Chronic Kidney Disease. AB - BACKGROUND: Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS: We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m(2) of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS: A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was -0.9 ml per minute per 1.73 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (>= 90 ml per minute per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m(2), the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS: An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.). PMID- 26539837 TI - Impact of Laparoscopic Sleeve Gastrectomy on Weight Loss and Associated Comorbidities in Adolescents and Young Adults. AB - BACKGROUND: Obesity is a common disease affecting young adults and adolescents worldwide. This study aims to delineate the role of laparoscopic sleeve gastrectomy (LSG) in weight loss and associated comorbidities to adolescents and young adults. PATIENTS AND METHODS: This study is a retrospective analysis of a prospective cohort of all young adults 16-22 years old who underwent LSG for morbid obesity and were followed up for 24 months. Demographic data, weight loss, and the status of several comorbidities, such as diabetes mellitus, hypertension, and dyslipidemia, were assessed at postoperative Months 1, 3, 6, 12, 18, and 24. RESULTS: Overall, at baseline and after 24 months of close follow-up of 37 adolescents and young adults who had undergone LSG, the body mass index of the patients was 46.93 +/- 6.07 kg/m(2) versus 26.2 +/- 3.6 kg/m(2) (P < .001), and the body weight was 143 +/- 29 kg versus 78 +/- 15 kg (P < .001). From the first follow-up visit after operation to the last one at the 24 months, there was also a significant difference in percentage excess weight loss (22.40 +/- 6.58% versus 81 +/- 17%; P < .001), body mass index difference (-5.47 +/- 1.69 kg/m(2) versus 18.08 +/- 4.38 kg/m(2); P < .001), and percentage excess body mass index loss (26.06 +/- 7.56% versus 96 +/- 21%; P < .001). The percentage of the adolescents and young adults with diabetes mellitus, hypertension, and dyslipidemia were diminished gradually at 6 months postoperatively (P < .001). CONCLUSIONS: LSG represents a safe and attractive treatment strategy for morbidly obese adolescents and young adults with comorbidities. In this study group excellent resolution of excess weight and comorbid conditions is achieved 2 years after LSG. PMID- 26539839 TI - Dental treatment injuries in the Finnish Patient Insurance Centre in 2000-2011. AB - Objective The Patient Insurance Centre in Finland reimburses patients who sustained injuries associated with medical and dental care without having to demonstrate malpractice. The aim was to analyse all dental injuries claimed through the Patient Insurance Centre over a 12-year period in order to identify factors affecting reimbursement of claims. Methods This study investigated all dental patient insurance claims in Finland during 2000-2011. The injury cases were grouped as (K00-K08) according to the International Classification of Diseases (ICD-10). Calendar year, claimant's age and gender, dental disease group and health service sector were the explanatory factors and the outcome was the decision of a claim. Multiple logistic regression modelling was used in the statistical analyses. Results The total number of decisions related to dental claims at the PIC in 2000-2011 was 7662, of which women claimed a clear majority (72%). Diseases of the pulp and periapical tissues (K04) and dental caries (K02) were the major disease groups (both 29%). Of the claims 40% were eligible for reimbursement, 27% were classified as insignificant or unavoidable injuries and 32% were rejected for other reasons. The proportion of reimbursed claims declined during the period. Patients from the private sector were more likely to be eligible for compensation than were those from the public sector (OR = 1.89, 95% CI = 1.71-2.10). Conclusions The number of dental patient insurance claims in Finland clearly rose, while the proportion of reimbursed claims declined. More claims received compensation in the private sector than in the public sector. PMID- 26539838 TI - Breast Cancer beyond the Age of Mutation. AB - Age is the greatest risk factor for breast cancer, but the reasons underlying this association are unclear. While there is undeniably a genetic component to all cancers, the accumulation of mutations with age is insufficient to explain the age-dependent increase in breast cancer incidence. In this viewpoint, we propose a multilevel framework to better understand the respective roles played by somatic mutation, microenvironment, and epigenetics making women more susceptible to breast cancer with age. The process of aging is associated with gradual breast tissue changes that not only corrupt the tumor-suppressive activity of normal tissue but also impose age-specific epigenetic changes that alter gene expression, thus reinforcing cellular phenotypes that are associated with a continuum of age-related tissue microenvironments. The evidence discussed here suggests that while the riddle of whether epigenetics drives microenvironmental changes, or whether changes in the microenvironment alter heritable cellular memory has not been solved, a path has been cleared enabling functional analysis leading to the prediction of key nodes in the network that link the microenvironment with the epigenome. The hypothesis that the accumulation of somatic mutations with age drives the age-related increase in breast cancer incidence, if correct, has a somewhat nihilistic conclusion, namely that cancers will be impossible to avoid. Alternatively, if microenvironment driven epigenetic changes are the key to explaining susceptibility to age-related breast cancers, then there is hope that primary prevention is possible because epigenomes are relatively malleable. PMID- 26539840 TI - Spontaneous Pattern Formation Induced by Benard-Marangoni Convection for Sol-Gel Derived Titania Dip-Coating Films: Effect of Co-solvents with a High Surface Tension and Low Volatility. AB - Evaporation-driven surface tension gradient in the liquid layer often causes the convective flow, i.e., Benard-Marangoni convection, resulting in the formation of cell-like patterns on the surface. Here, we prepared sol-gel-derived titania films from Ti(OC3H7(i))4 solutions by dip coating and discussed the effect of the addition of co-solvents with a high surface tension and low volatility on the spontaneous pattern formation induced by Benard-Marangoni convection. Propylene glycol (PG, with a surface tension of 38.6 mN m(-1)) and dipropylene glycol (DPG, with a surface tension of 33.9 mN m(-1)) were added to the coating solutions containing 2-propanol (2-Pr, with a surface tension of 22.9 mN m(-1)) for controlling the evaporation-driven surface tension gradient in the coating layer on a substrate. During dip coating at a substrate withdrawal speed of 50 cm min( 1) in a thermostatic oven at 60 degrees C, linearly arranged cell-like patterns on a micrometer scale were spontaneously formed on the titania gel films, irrespective of the composition of coating solutions. Such surface patterns remained even after the heat treatment at 200 and 600 degrees C, where the densification and crystallization of the titania films progressed. The width and height of the cell-like patterns increased with increasing PG and DPG contents in the coating solutions, where the addition of PG resulted in the formation of cells with a larger height than DPG. PMID- 26539841 TI - The complete mitochondrial genome of the king horseshoe bat (Rhinolophus rex) using next-generation sequencing and Sanger sequencing. AB - The king horseshoe bat (Rhinolophus rex) is endemic to China. Here, we characterized the complete mitochondrial genome of R. rex using next-generation sequencing and Sanger sequencing. The mitogenome is 16 845 bp in length and contains 22 tRNAs, two rRNAs, 13 protein-coding genes, and a non-coding control region. Our traditional Sanger sequencing verified that mtDNA sequences generated from next-generation sequencing are reliable. The mitogenome of R. rex will be useful for the conservation genetics of this endangered species. PMID- 26539842 TI - A new concept for molecular engineering of artificial enzymes: a multiscale simulation. AB - We propose a new concept for the design of artificial enzymes from synthetic protein-like copolymers and non-natural functional monomers which in terms of their affinity for water can be divided into two categories: hydrophobic and hydrophilic. Hydrophilic monomers comprise catalytically active groups similar to those in the corresponding amino acid residues. A key ingredient of our approach is that the target globular conformation of protein-like, core-shell morphology with multiple catalytic groups appears spontaneously in the course of controlled radical polymerization in a selective solvent. As a proof of concept, we construct a fully synthetic analog of serine hydrolase, e.g.alpha-chymotrypsin, using the conformation-dependent sequence design approach and multiscale simulation that combines the methods of "mesoscale chemistry" and atomistic molecular dynamics (MD). A 100 ns GPU-accelerated MD simulation of the designed polymer-supported catalyst in the aqueous environment provides valuable information on the structural organization of this system that has been synthesized in our Lab. PMID- 26539843 TI - 3D Shape Matching via Two Layer Coding. AB - View-based 3D shape retrieval is a popular branch in 3D shape analysis owing to the high discriminative property of 2D views. However, many previous works do not scale up to large 3D shape databases. We propose a two layer coding (TLC) framework to conduct shape matching much more efficiently. The first layer coding is applied to pairs of views represented as depth images. The spatial relationship of each view pair is captured with so-called eigen-angle, which is the planar angle between the two views measured at the center of the 3D shape. Prior to the second layer coding, the view pairs are divided into subsets according to their eigen-angles. Consequently, view pairs that differ significantly in their eigen-angles are encoded with different codewords, which implies that spatial arrangement of views is preserved in the second layer coding. The final feature vector of a 3D shape is the concatenation of all the encoded features from different subsets, which is used for efficient indexing directly. TLC is not limited to encode the local features from 2D views, but can be also applied to encoding 3D features. Exhaustive experimental results confirm that TLC achieves state-of-the-art performance in both retrieval accuracy and efficiency. PMID- 26539844 TI - Capturing Spatial Interdependence in Image Features: The Counting Grid, an Epitomic Representation for Bags of Features. AB - In recent scene recognition research images or large image regions are often represented as disorganized "bags" of features which can then be analyzed using models originally developed to capture co-variation of word counts in text. However, image feature counts are likely to be constrained in different ways than word counts in text. For example, as a camera pans upwards from a building entrance over its first few floors and then further up into the sky Fig. 1 Fig. 1. Feature counts change slightly as the field of view moves. For example, the abundance of the "car" features is reduced, but the counts of the features found on building facades are increased. The counting grid model accounts for such changes naturally, and it can also account for images of different scenes. PMID- 26539845 TI - Co-Segmentation Guided Hough Transform for Robust Feature Matching. AB - We present an algorithm that integrates image co-segmentation into feature matching, and can robustly yield accurate and dense feature correspondences. Inspired by the fact that correct feature correspondences on the same object typically have coherent transformations, we cast the task of feature matching as a density estimation problem in the homography space. Specifically, we project the homographies of correspondence candidates into the parametric Hough space, in which geometric verification of correspondences can be activated by voting. The precision of matching is then boosted. On the other hand, we leverage image co segmentation, which discovers object boundaries, to determine relevant voters and speed up Hough voting. In addition, correspondence enrichment can be achieved by inferring the concerted homographies that are propagated between the features within the same segments. The recall is hence increased. In our approach, feature matching and image co-segmentation are tightly coupled. Through an iterative optimization process, more and more correct correspondences are detected owing to object boundaries revealed by co-segmentation. The proposed approach is comprehensively evaluated. Promising experimental results on four datasets manifest its effectiveness. PMID- 26539846 TI - Deep Human Parsing with Active Template Regression. AB - In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28]. PMID- 26539847 TI - Efficient Optimization for Sparse Gaussian Process Regression. AB - We propose an efficient optimization algorithm to select a subset of training data as the inducing set for sparse Gaussian process regression. Previous methods either use different objective functions for inducing set and hyperparameter selection, or else optimize the inducing set by gradient-based continuous optimization. The former approaches are harder to interpret and suboptimal, whereas the latter cannot be applied to discrete input domains or to kernel functions that are not differentiable with respect to the input. The algorithm proposed in this work estimates an inducing set and the hyperparameters using a single objective. It can be used to optimize either the marginal likelihood or a variational free energy. Space and time complexity are linear in training set size, and the algorithm can be applied to large regression problems on discrete or continuous domains. Empirical evaluation shows state-of-art performance in discrete cases, competitive prediction results as well as a favorable trade-off between training and test time in continuous cases. PMID- 26539848 TI - Finding the Secret of Image Saliency in the Frequency Domain. AB - There are two sides to every story of visual saliency modeling in the frequency domain. On the one hand, image saliency can be effectively estimated by applying simple operations to the frequency spectrum. On the other hand, it is still unclear which part of the frequency spectrum contributes the most to popping-out targets and suppressing distractors. Toward this end, this paper tentatively explores the secret of image saliency in the frequency domain. From the results obtained in several qualitative and quantitative experiments, we find that the secret of visual saliency may mainly hide in the phases of intermediate frequencies. To explain this finding, we reinterpret the concept of discrete Fourier transform from the perspective of template-based contrast computation and thus develop several principles for designing the saliency detector in the frequency domain. Following these principles, we propose a novel approach to design the saliency detector under the assistance of prior knowledge obtained through both unsupervised and supervised learning processes. Experimental results on a public image benchmark show that the learned saliency detector outperforms 18 state-of-the-art approaches in predicting human fixations. PMID- 26539849 TI - Gaussian-Based Hue Descriptors. AB - A robust and accurate hue descriptor that is useful in modeling human color perception and for computer vision applications is explored. The hue descriptor is based on the peak wavelength of a Gaussian-like function (called a wraparound Gaussian) and is shown to correlate as well as CIECAM02 hue to the hue designators of papers from the Munsell and Natural Color System color atlases and to the hue names found in Moroney's Color Thesaurus. The new hue descriptor is also shown to be significantly more stable under a variety of illuminants than CIECAM02. The use of wraparound Gaussians as a hue model is similar in spirit to the use of subtractive Gaussians proposed by Mizokami et al., but overcomes many of their limitations. PMID- 26539850 TI - GReTA-A Novel Global and Recursive Tracking Algorithm in Three Dimensions. AB - Tracking multiple moving targets allows quantitative measure of the dynamic behavior in systems as diverse as animal groups in biology, turbulence in fluid dynamics and crowd and traffic control. In three dimensions, tracking several targets becomes increasingly hard since optical occlusions are very likely, i.e., two featureless targets frequently overlap for several frames. Occlusions are particularly frequent in biological groups such as bird flocks, fish schools, and insect swarms, a fact that has severely limited collective animal behavior field studies in the past. This paper presents a 3D tracking method that is robust in the case of severe occlusions. To ensure robustness, we adopt a global optimization approach that works on all objects and frames at once. To achieve practicality and scalability, we employ a divide and conquer formulation, thanks to which the computational complexity of the problem is reduced by orders of magnitude. We tested our algorithm with synthetic data, with experimental data of bird flocks and insect swarms and with public benchmark datasets, and show that our system yields high quality trajectories for hundreds of moving targets with severe overlap. The results obtained on very heterogeneous data show the potential applicability of our method to the most diverse experimental situations. PMID- 26539851 TI - Kernel Methods on Riemannian Manifolds with Gaussian RBF Kernels. AB - In this paper, we develop an approach to exploiting kernel methods with manifold valued data. In many computer vision problems, the data can be naturally represented as points on a Riemannian manifold. Due to the non-Euclidean geometry of Riemannian manifolds, usual Euclidean computer vision and machine learning algorithms yield inferior results on such data. In this paper, we define Gaussian radial basis function (RBF)-based positive definite kernels on manifolds that permit us to embed a given manifold with a corresponding metric in a high dimensional reproducing kernel Hilbert space. These kernels make it possible to utilize algorithms developed for linear spaces on nonlinear manifold-valued data. Since the Gaussian RBF defined with any given metric is not always positive definite, we present a unified framework for analyzing the positive definiteness of the Gaussian RBF on a generic metric space. We then use the proposed framework to identify positive definite kernels on two specific manifolds commonly encountered in computer vision: the Riemannian manifold of symmetric positive definite matrices and the Grassmann manifold, i.e., the Riemannian manifold of linear subspaces of a Euclidean space. We show that many popular algorithms designed for Euclidean spaces, such as support vector machines, discriminant analysis and principal component analysis can be generalized to Riemannian manifolds with the help of such positive definite Gaussian kernels. PMID- 26539852 TI - Learning Hierarchical Space Tiling for Scene Modeling, Parsing and Attribute Tagging. AB - A typical scene category contains an enormous number of distinct scene configurations that are composed of objects and regions of varying shapes in different layouts. In this paper, we first propose a representation named hierarchical space tiling (HST) to quantize the huge and continuous scene configuration space. Then, we augment the HST with attributes (nouns and adjectives) to describe the semantics of the objects and regions inside a scene. We present a weakly supervised method for simultaneously learning the scene configurations and attributes from a collection of natural images associated with descriptive text. The precise locations of attributes are unknown in the input and are mapped to the HST nodes through learning. Starting with a full HST, we iteratively estimate the HST model under a learning-by-parsing framework. Given a test image, we compute the most probable parse tree with the associated attributes by dynamic programming. We quantitatively analyze the representative efficiency of HST, show the learned representation is less ambiguous and has semantically meaningful inner concepts. In applications, we apply our model to four tasks: scene classification, attribute recognition, attribute localization, and pixel-wise scene labeling, and show the performance improvements as well as higher efficiency. PMID- 26539853 TI - Maurer-Cartan Forms for Fields on Surfaces: Application to Heart Fiber Geometry. AB - We study the space of first order models of smooth frame fields using the method of moving frames. By exploiting the Maurer-Cartan matrix of connection forms we develop geometrical embeddings for frame fields which lie on spherical, ellipsoidal and generalized helicoid surfaces. We design methods for optimizing connection forms in local neighborhoods and apply these to a statistical analysis of heart fiber geometry, using diffusion magnetic resonance imaging. This application of moving frames corroborates and extends recent characterizations of muscle fiber orientation in the heart wall, but also provides for a rich geometrical interpretation. In particular, we can now obtain direct local measurements of the variation of the helix and transverse angles, of fiber fanning and twisting, and of the curvatures of the heart wall in which these fibers lie. PMID- 26539854 TI - Multimodal Manifold Analysis by Simultaneous Diagonalization of Laplacians. AB - We construct an extension of spectral and diffusion geometry to multiple modalities through simultaneous diagonalization of Laplacian matrices. This naturally extends classical data analysis tools based on spectral geometry, such as diffusion maps and spectral clustering. We provide several synthetic and real examples of manifold learning, object classification, and clustering, showing that the joint spectral geometry better captures the inherent structure of multi modal data. We also show the relation of many previous approaches for multimodal manifold analysis to our framework. PMID- 26539855 TI - Multispectral Joint Image Restoration via Optimizing a Scale Map. AB - Color, infrared and flash images captured in different fields can be employed to effectively eliminate noise and other visual artifacts. We propose a two-image restoration framework considering input images from different fields, for example, one noisy color image and one dark-flashed near-infrared image. The major issue in such a framework is to handle all structure divergence and find commonly usable edges and smooth transitions for visually plausible image reconstruction. We introduce a novel scale map as a competent representation to explicitly model derivative-level confidence and propose new functions and a numerical solver to effectively infer it following our important structural observations. Multispectral shadow detection is also used to make our system more robust. Our method is general and shows a principled way to solve multispectral restoration problems. PMID- 26539856 TI - Multi-View Intact Space Learning. AB - It is practical to assume that an individual view is unlikely to be sufficient for effective multi-view learning. Therefore, integration of multi-view information is both valuable and necessary. In this paper, we propose the Multi view Intact Space Learning (MISL) algorithm, which integrates the encoded complementary information in multiple views to discover a latent intact representation of the data. Even though each view on its own is insufficient, we show theoretically that by combing multiple views we can obtain abundant information for latent intact space learning. Employing the Cauchy loss (a technique used in statistical learning) as the error measurement strengthens robustness to outliers. We propose a new definition of multi-view stability and then derive the generalization error bound based on multi-view stability and Rademacher complexity, and show that the complementarity between multiple views is beneficial for the stability and generalization. MISL is efficiently optimized using a novel Iteratively Reweight Residuals (IRR) technique, whose convergence is theoretically analyzed. Experiments on synthetic data and real-world datasets demonstrate that MISL is an effective and promising algorithm for practical applications. PMID- 26539857 TI - Optimizing Average Precision Using Weakly Supervised Data. AB - Many tasks in computer vision, such as action classification and object detection, require us to rank a set of samples according to their relevance to a particular visual category. The performance of such tasks is often measured in terms of the average precision (ap). Yet it is common practice to employ the support vector machine ( svm) classifier, which optimizes a surrogate 0-1 loss. The popularity of svmcan be attributed to its empirical performance. Specifically, in fully supervised settings, svm tends to provide similar accuracy to ap-svm, which directly optimizes an ap-based loss. However, we hypothesize that in the significantly more challenging and practically useful setting of weakly supervised learning, it becomes crucial to optimize the right accuracy measure. In order to test this hypothesis, we propose a novel latent ap-svm that minimizes a carefully designed upper bound on the ap-based loss function over weakly supervised samples. Using publicly available datasets, we demonstrate the advantage of our approach over standard loss-based learning frameworks on three challenging problems: action classification, character recognition and object detection. PMID- 26539858 TI - Scale and Rotation Invariant Matching Using Linearly Augmented Trees. AB - We propose a novel linearly augmented tree method for efficient scale and rotation invariant object matching. The proposed method enforces pairwise matching consistency defined on trees, and high-order constraints on all the sites of a template. The pairwise constraints admit arbitrary metrics while the high-order constraints use L1 norms and therefore can be linearized. Such a linearly augmented tree formulation introduces hyperedges and loops into the basic tree structure. But, different from a general loopy graph, its special structure allows us to relax and decompose the optimization into a sequence of tree matching problems that are efficiently solvable by dynamic programming. The proposed method also works on continuous scale and rotation parameters; we can match with a scale up to any large value with the same efficiency. Our experiments on ground truth data and a variety of real images and videos show that the proposed method is efficient, accurate and reliable. PMID- 26539859 TI - Semantic-Aware Co-Indexing for Image Retrieval. AB - In content-based image retrieval, inverted indexes allow fast access to database images and summarize all knowledge about the database. Indexing multiple clues of image contents allows retrieval algorithms search for relevant images from different perspectives, which is appealing to deliver satisfactory user experiences. However, when incorporating diverse image features during online retrieval, it is challenging to ensure retrieval efficiency and scalability. In this paper, for large-scale image retrieval, we propose a semantic-aware co indexing algorithm to jointly embed two strong cues into the inverted indexes: 1) local invariant features that are robust to delineate low-level image contents, and 2) semantic attributes from large-scale object recognition that may reveal image semantic meanings. Specifically, for an initial set of inverted indexes of local features, we utilize semantic attributes to filter out isolated images and insert semantically similar images to this initial set. Encoding these two distinct and complementary cues together effectively enhances the discriminative capability of inverted indexes. Such co-indexing operations are totally off-line and introduce small computation overhead to online retrieval, because only local features but no semantic attributes are employed for the query. Hence, this co indexing is different from existing image retrieval methods fusing multiple features or retrieval results. Extensive experiments and comparisons with recent retrieval methods manifest the competitive performance of our method. PMID- 26539860 TI - Shortest Paths with Higher-Order Regularization. AB - This paper describes a new method of finding thin, elongated structures in images and volumes. We use shortest paths to minimize very general functionals of higher order curve properties, such as curvature and torsion. Our method uses line graphs to find the optimal path on a given discretization, often in the order of seconds on a single computer. The curves are then refined using local optimization making it possible to recover very smooth curves. We are able to place constraints on our curves such as maximum integrated curvature, or a maximum curvature at any point of the curve. To our knowledge, we are the first to perform experiments in three dimensions with curvature and torsion regularization. The largest graphs we process have over a hundred billion arcs. Experiments on medical images and in multi-view reconstruction show the significance and practical usefulness of higher order regularization. PMID- 26539862 TI - [Transcriptomics and proteomics in studies of induced differentiation of leukemia cells]. AB - Induced differentiation of leukemia cells is in the focus of basic and applied biomedical studies medicine and biology for more than 30 years. During this period specific regulatory molecules involved in the maturation process have been identified by biochemical and molecular biological methods. Recent developments of high-throughput transcriptomic and proteomic techniques made it possible to analyze large sets of mRNA and proteins; this resulted in identification of functionally important signal transduction pathways and networks of molecular interactions, and thus extent existing knowledge on the molecular mechanisms of induced differentiation. Despite significant advances in mechanisms of induced differentiation, many problems related to the molecular mechanism of cell maturation, a phenomenon of therapeutic resistance of leukemic cells need better understanding and thus require further detailed study. Transcriptomics and proteomics methods provide a suitable methodological platform for the implementation of such studies. This review highlights the use of transcriptomic and proteomic methods in studies aimed at various aspects of the induced differentiation. Special attention is paid to the employment of the systems approach for investigation of various aspects of cell maturation. The use of the systems approach in studies of induced differentiation is an important step for the transition from the formal data accumulation on expression of mRNA and proteins towards creating models of biological processes in silico. PMID- 26539863 TI - [Problems and prospects of creation of extracorporal systems for support of functional livers status]. AB - The review considers features of efferent therapy employing extracorporeal systems, the devices known as "artificial liver" and "bioartificial liver" in the treatment of liver insufficiency. Analysis of literature data shows the need for further development of these biomedical studies and the search for optimal solutions in the selection of the source of hepatocytes, the development of bioreactors and biomaterials forming the basis of devices like "bioartificial liver". Taking into consideration certain advantages and disadvantages typical for various methods of extracorporeal support of the functional state of the liver one can evaluate prior experience in the treatment of liver diseases and approaches to the development of new, more effective medical technologies. PMID- 26539864 TI - [Role of innate immunity in tolerance induction]. AB - This review considers the role of innate immunity in mechanisms of transplant tolerance and rejection, analyse the role of innate immunity cells (dendritic cells-DC, NK, must and other cells) in these processes, and the pathes of creation of tolerogenic DC for transplant rejection therapy and tolerance. PMID- 26539865 TI - [Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development]. AB - Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. "Angiogenic switch" is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and "non-VEGF dependent", or alternative, angiogenic pathways that constitute the prospect of future research in the field. PMID- 26539866 TI - [Influence of resveratrol and dihydroquercetin inclusion into phospholipid nanopatricles on their bioavailability and specific activity]. AB - The effects of natural polyphenols, resveratrol (RES) and dihydroquercetin (DHQ), included in phospholipid nanoparticles, have been compared with free substances of RES and DHQ in in vitro and in vivo experiments. Preincubation of healthy donor plasma low density lipoproteins (LDL) with RES or DHQ included in phospholipid nanoparticles caused a more pronounced decrease in Cu2+ induced lipid oxidation compared with the free substances, and reduced the formation of lipid peroxides products. Bioavailabilities of RES and DHQ in phospholipid formulations after oral administration in rats were increased by 1.5-2 times. In an acute hypoxia model in mice prophylactic two-week administration of RES or DHQ phospholipid formulations resulted in 25% increase in survival and 1.5-fold increase in catalase activity in brain homogenates compared to free substances. Using the model of endothelial dysfunction in rats induced by L-NAME it was shown, that RES markedly attenuated the inhibition effect of L-NAME on NO synthesis. RES in phospholipid nanoparticles had the same action at a dose 10 times lower compared to free RES. Load test with resistance (clamping of the ascending aorta for 30 sec) showed that phospholipid formulation of RES possessed more pronounced protective effect due to the stimulation of endothelial NO synthase. PMID- 26539867 TI - [The molecular mechanisms of platelets activation in patients with cerebrovascular disease]. AB - Cerebrovascular disease is a main cause of mortality and one of the big medical problems. After the vascular wall's damage the endothelial cells secrete the von Willebrand factor which then connects with its platelet's receptor GP Ib-V-IX. There are two polymorphisms Thr145Met and T(-5)C of the GP Iba gene associated with arterial thrombosis development. Also the difference in platelets' genes expressions was shown in patients with various clinical course of ischemic heart disease. The aim of this study was to investigate the role of platelet's receptor for von Willebrand factor in platelets' activation in patients with cerebrovascular disease. 123 patients with cerebrovascular disease and 97 healthy donors were included into the study. We analyzed the level of receptor for von Willebrand factor on platelet's membrane by flow cytometry, Thr145Met and T(-5)C GP Iba polymorphiams by PCR-RFLP, the GP Iba gene expression by RT-PCR and ADP induced platelet aggregation by Born method. We have shown: 1) the 145Met GP Iba allele prevalence in patients with atherotrombotic stroke development due to macroangiopathy; 2) the pre-mRNA transform into the mature mRNA in activated platelets and this process may be stopped by the antiplatelet therapy by acetylsalicylic acid. PMID- 26539868 TI - [Determination of strontium content in whole blood and urine by icp-ms]. AB - Parameters of strontium determination in the whole blood and urine of children living near ore deposits containing up to 20% strontium sulfate have been determined. The average strontium content in the whole blood of two children groups of 109.52 +/- 11.07 mg/L and 131.62 +/- 12.95 mg/L, significantly exceeded the level in the comparison group 44.2 +/- 4.24 mg/L. The average strontium contents of two groups of children in urine were 1252.3 +/- 332.2 mg/L and 1341.5 +/- 241.8 mg/L, these values were 4.2 and 4.5 times higher than in the comparison group 296.4 +/- 61.5 mg/L. The conditions for blood and urine sample preparation were optimized to reduce measure errors and to determine strontium at the reference concentration level. The accuracy of the results has been confirmed by analysis of the standard samples SeronormTM Whole Blood L1, L2, L3 and SeronormTM Urine. PMID- 26539869 TI - [Experimental modeling of nucleoprotein disposal disorders in systemic lupus erythematosus]. AB - The objective of this research was to adapt the experimental model simulating the nucleoprotein disposal disorders in systemic lupus erythematosus (SLE) for further study of its extracorporeal correction, as well as to assess validity of the model by short-term experiment. Twenty to female Wistar rats were intraperitoneally injected with the chromatin-containing extract from bovine liver followed by intravenous administration of anti-DNA antibodies derived from SLE patients. After these procedures plasma concentrations of anti-dsDNA, circulating immune complexes and DNA became sharply increased, together with distinct elevation of leukocytes. On the contrary, changes in erythrocytes, platelets, total protein concentration, creatinine, asparagine and alanine aminotransferase activities, as well as blood coagulation time were changed insignificantly. Using direct immunofluorescence of cryosections, we detected human IgG deposition in rat kidneys treated in accordance with the simulation protocol. Thus, our model reproduces essential DNA disposal disorders in SLE without any animal death or the life-threatening changes in examined markers during short-term experiment. PMID- 26539870 TI - [Extracorporeal treatment of nucleoprotein disposal disorders using the systemic lupus erythematosus model: evaluation of efficacy and safety in a short-term simulated experiment]. AB - Efficacy and safety of the extracorporeal blood perfusion through DNase I- and C1q-containing magnetic beads have been evaluated using the experimental model simulating the nucleoprotein disposal disorders in systemic lupus erythematosus (SLE). The study was performed using 20 rats in which the essential impairments of nucleoprotein catabolism typical for SLE were modeled. The animals were randomized into the experimental group and the placebo perfusion control group. Rats of the experimental group were characterized by the statistically significant reduction of increased levels of circulating immune complexes and plasma DNA as well as diminished levels of plasma creatinine and kidney IgG deposition as compared with placebo controls. During short-term experiment there were neither animal deaths nor substantial blood cell destruction and hepatotoxicity signs. PMID- 26539871 TI - [Determination of glutamic acid in biological material by capillary electrophoresis]. AB - The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy. PMID- 26539872 TI - [Influence of gravity discharge on the content of isatin-binding proteins in mice: results of ground-based and space research under the program Bion-M No1]. AB - Isatin-binding activity of mice liver proteins has been investigated in the samples from the control and flight groups by using the methods of biosensor and proteomic analysis. It was found the higher isatin-binding activity in mice of flight group. The content of a number of individual isatin-binding proteins in the samples of the flight groups differ slightly from the ground control. However, in samples from animals which have weekly post-flight adaptation, the level of certain proteins was significantly increased. The latter allows us to assume that the main events in the proteome of mice (at least in subproteome of isatin-binding proteins), occurs in early post-flight period. PMID- 26539873 TI - [Pharmacokinetic and analgesic properties of the injectable dosage form of a new imidazobenzimidazole derivative RU-1205 with kappa agonist activity]. AB - Pharmacokinetic properties of imidazobenzimidazole derivative compound RU-1205 were investigated after subcutaneous administration to rabbits as a substance and a dosage form (lyophilisates for injection) at a dose of 25 mg/kg. The lyophilisate was characterized by high values of the relative bioavailability. In tests, the "hot plate" and "vinegar cramps" the dosage form and the substance exhibited the same analgesic effect. PMID- 26539874 TI - [Effect of melaxen on free radical processes intensity and some antioxidant enzymes activity in rats liver and blood serum under type 2 diabetes mellitus]. AB - The effect of melaxen on free radical processes and activity of superoxide dismutase and catalase in rats with type 2 diabetes mellitus (T2DM) has been investigated. It was established that melaxen administration to diabetic rats caused a decrease of the intensity of free radical processes as evidenced a decrease of the lipid peroxidation primary products content and biochemiluminescence parameters. The activity of the antioxidant enzymes changed towards normal values. These effects were probably induced by the correction of the melatonin level at the result of the melaxen action. PMID- 26539875 TI - [Recombinant cephalosporin-acid synthesase: optimisation of expression in E.coli cells, immobilisation and application for biocatalytic cefazolin synthesis]. AB - Cephalosporin acid synthetase (CASA) is responsible for specific to synthesis of cephalosporin-acids, its expression in Escherichia coli cells is accompanied by accumulation of unprocessed insoluble precursor. In order to optimize conditions of recombinant CASA production we have studied the effects of several parameters of strain cultivation, including growth media composition, temperature, and inoculation dose. Also plasmids for production of CASA variants with the signal sequence of Erwinia carotovora L-asparaginase (ansCASA) and "leaderless" CASA were created in search of more efficient expression constructs. Removal of the N terminal secretion signal sequence reduced the production of functionally active CASA more than 10-fold and inhibited strain growth. Insertion of the L asparaginase signal sequence increased the specific enzyme activity in the resultant recombinant strain. The ansCASA producing strain was used to develop the method of immobilization of the recombinant enzyme on an epoxy-activated macroporous acrylic support. The resultant biocatalyst performed effective synthesis of cefazolin from 3-[(5-methyl-1,3,4-thiadiazol-2-il)-thiomethyl]-7- aminocephalosporanic acid (MMTD-7-ACA) and methyl ester of 1(H)-tetrazolilacetic acid (METzAA), under mild conditions a transformation level of MMTD-7-ACA to cefazolin of 95% is reached. PMID- 26539876 TI - [An antitumor osteotropic agent based on tumor necrosis factor]. AB - A novel drug for treatment of bone metastases based on human recombinant tumor necrosis factor (TNF-alpha) has been designed. The drug is a molecular structure containing yeast double-stranded ribonucleic acid (dsRNA) covered by the conjugate of polyanion dextran with TNF-alpha and bisphosphonate, alendronic acid. The structure is characterized by the combination of substances possessing antitumor activity (TNF-alpha, dsRNA) and a vector molecule (bisphosphonate) providing tropism to hydroxyapatite, the main mineral component of the bone tissue matrix. The conjugation conditions were optimized and the conjugates of TNF-alpha and alendronic acid with dextran were synthesized. Molecular structures were obtained by self-assembly, and the resulting complexes were separated by gel filtration on Sepharose CL-6B. The electrophoretic analysis method revealed decreased mobility of dsRNA in the complex with the conjugate as compared to the mobility of the original dsRNA. This confirms formation of the designed structures. Transmission electron microscopy confirmed the presence of particles with sizes of 30-40 nm in the drug. Evaluation by the sorption/desorption method showed a higher affinity of TNF-alpha conjugates to hydroxyapatite as compared to the original TNF-alpha molecules (from 1.0 to 1.8 mol/L vs. 0.3 mol/L of potassium phosphate buffer for desorption, respectively). PMID- 26539877 TI - [Effect of reboxetine on activity of carboxypeptidase E in the nerve tissue of rats]. AB - Depression is one of the most common mental disorders, but its etiology is not completely understood. It is assumed that peptidergic system components are involved in the formation of this pathology. Neuropeptides play an important role in the regulation of mental and emotional states. Sarboxypeptidase E is a key enzyme of peptide processing; it regulates neuropeptide levels in the various structures of the nervous system. We have studied effects of a single dose of reboxetine on the activity of carboxypeptidase E in various brain regions and the adrenal glands of rats. The reboxetine injection decreased carboxypeptidase E activity in the pituitary gland (12 h after injection), in the pituitary gland, the quadrigeminal bodies, the medulla oblongata, the hypothalamus, the hippocampus and the amygdala (24 h after injection), in the pituitary gland and striatum (72 h after injection). The enzyme activity in adrenal glands remained basically unchanged. Apparently, the decrease of carboxypeptidase E activity may influence the level of regulatory peptides involved in the pathogenesis of depression. PMID- 26539878 TI - Pair housing of Vervets/African Green Monkeys for biomedical research. AB - Vervets, also known as African green monkeys, are a nonhuman primate species widely used in biomedical research. However, there are currently few references available describing techniques and rates of success for pair-housing this species. We present data from four cohorts of vervets from three different facilities: (i) the Wake Forest Vervet Research Colony (VRC; n = 72 female pairs, n= 52 male pairs), (ii) the University of Louisiana at Lafayette-New Iberia Research Center (UL-NIRC; n = 57 female pairs, n = 54 male pairs), (iii) the Tulane National Primate Research Center (TNRPC; n = 18 male pairs), and (iv) a cohort of imported males (n = 18 pairs) at Wake Forest. Compatibility was measured at 14, 30, and 60 days following introduction. Success rates for pair housing at 14 days ranged from 96% to 98% for females and 96% to 100% for males at the VRC and UL-NIRC but were lower in the smaller imported male cohorts (TNPRC: 50%; WF: 28%). Among the UL-NIRC cohort and VRC male cohort, most of the pair separations after 14 days were due to reasons unrelated to social incompatibility. In contrast, a large proportion of TNPRC and imported male pairs successful at 14 days required separation within 60 days due to incompatibility. Multiple logistic regressions were performed using cohort, mean age of pair and weight difference between pair-mates as potential predictors of compatibility at 14 days. All three predicted the 14-day outcome in males but not females. A separate analysis in the VRC cohort found no evidence that prior familiarity in a group setting influenced outcomes. Variations in success rates across cohorts may have been influenced by introduction methodology. Behavioral differences between vervets and macaques, coupled with our findings, lead us to theorize that the gradual introduction techniques commonly implemented to pair house macaques may not be beneficial or suitable for this species. Am. J. Primatol. 79:e22501, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26539880 TI - Three-Dimensional Quantum Confinement of Charge Carriers in Self-Organized AlGaN Nanowires: A Viable Route to Electrically Injected Deep Ultraviolet Lasers. AB - We report on the molecular beam epitaxial growth and structural characterization of self-organized AlGaN nanowire arrays on Si substrate with high luminescence efficiency emission in the deep ultraviolet (UV) wavelength range. It is found that, with increasing Al concentration, atomic-scale compositional modulations can be realized, leading to three-dimensional quantum confinement of charge carriers. By further exploiting the Anderson localization of light, we have demonstrated, for the first time, electrically injected AlGaN lasers in the deep UV band operating at room temperature. The laser operates at ~289 nm and exhibits a threshold of 300 A/cm(2), which is significantly smaller compared to the previously reported electrically injected AlGaN multiple quantum well lasers. PMID- 26539881 TI - Outcomes One and Two Winters Following Cognitive-Behavioral Therapy or Light Therapy for Seasonal Affective Disorder. AB - OBJECTIVE: The central public health challenge for winter seasonal affective disorder (SAD) is recurrence prevention. Preliminary studies suggest better long term outcomes following cognitive-behavioral therapy tailored for SAD (CBT-SAD) than light therapy. The present study is a large, randomized head-to-head comparison of these treatments on outcomes one and two winters after acute treatment. METHOD: Community adults with major depression, recurrent with seasonal pattern (N=177) were followed one and two winters after a randomized trial of 6 weeks of CBT-SAD (N=88) or light therapy (N=89). Prospective follow-up visits occurred in January or February of each year, and major depression status was assessed by telephone in October and December of the first year. The primary outcome was winter depression recurrence status on the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD). Other outcomes were depression severity on the SIGH-SAD and the Beck Depression Inventory-Second Edition (BDI-II), remission status based on severity cutoff scores, and major depression status from tracking calls. RESULTS: The treatments did not differ on any outcome during the first year of follow-up. At the second winter, CBT-SAD was associated with a smaller proportion of SIGH-SAD recurrences (27.3% compared with 45.6%), less severe symptoms on both measures, and a larger proportion of remissions defined as a BDI-II score <=8 (68.3% compared with 44.5%) compared with light therapy. Nonrecurrence at the next winter was more highly associated with nonrecurrence at the second winter among CBT-SAD participants (relative risk=5.12) compared with light therapy participants (relative risk=1.92). CONCLUSIONS: CBT-SAD was superior to light therapy two winters following acute treatment, suggesting greater durability for CBT-SAD. PMID- 26539882 TI - General Formation of M-MoS3 (M = Co, Ni) Hollow Structures with Enhanced Electrocatalytic Activity for Hydrogen Evolution. AB - Complex molybdenum-based ternary or multinary sulfides hollow structures are developed via a fast precipitation process, together with a subsequent annealing treatment. Benefiting from the merits of high-curvature surfaces with excellent intrinsic catalytic activity, the obtained unique hollow structures exhibit enhanced performance as electrocatalysts for hydrogen production in acidic media. PMID- 26539883 TI - Looking into the Black Box of Synaptic Vesicle Recruitment. AB - To sustain ongoing synaptic transmission, new transmitter-filled vesicles must be recruited to empty release sites rapidly. However, in this issue of Neuron, Midorikawa and Sakaba (2015) show that, before being released, vesicles are tethered at the membrane for seconds. PMID- 26539884 TI - Sensory-Motor Circuits: Hox Genes Get in Touch. AB - Sensory-motor reflex circuits are the basic units from which animal nervous systems are constructed, yet little is known regarding how connections within these simple networks are established. In papers in Cell Reports and in this issue of Neuron, Zheng et al. (2015a, 2015b) demonstrate that coordinate activities of Hox genes in sensory neurons and interneurons govern connectivity within touch-reflex circuits in C. elegans. PMID- 26539879 TI - Phosphoproteomics in the Age of Rapid and Deep Proteome Profiling. PMID- 26539885 TI - Applying the Brakes: When to Stop Eating. AB - The nucleus accumbens regulates consummatory behaviors, such as eating. In this issue of Neuron, O'Connor et al. (2015) identify dopamine receptor 1-expressing neurons that project to the lateral hypothalamus as mediating rapid control over feeding behavior. PMID- 26539886 TI - New Eye-Tracking Techniques May Revolutionize Mental Health Screening. AB - Visually-guided behavior recruits a network of brain regions so extensive that it is often affected by neuropsychiatric disorders, producing measurable atypical oculomotor signatures. Wang et al. (2015) combine eye tracking with computational attention models to decipher the neurobehavioral signature of autism. PMID- 26539888 TI - New Views on the Misconstrued: Executioner Caspases and Their Diverse Non apoptotic Roles. AB - Initially characterized for their roles in apoptosis, executioner caspases have emerged as important regulators of an array of cellular activities. This is especially true in the nervous system, where sublethal caspase activity has been implicated in axonal pathfinding and branching, axonal degeneration, dendrite pruning, regeneration, long-term depression, and metaplasticity. Here we examine the roles of sublethal executioner caspase activity in nervous system development and maintenance, consider the mechanisms that locally activate and restrain these potential killers, and discuss how their activity be subverted in neurodegenerative disease. PMID- 26539887 TI - The Psychology and Neuroscience of Curiosity. AB - Curiosity is a basic element of our cognition, but its biological function, mechanisms, and neural underpinning remain poorly understood. It is nonetheless a motivator for learning, influential in decision-making, and crucial for healthy development. One factor limiting our understanding of it is the lack of a widely agreed upon delineation of what is and is not curiosity. Another factor is the dearth of standardized laboratory tasks that manipulate curiosity in the lab. Despite these barriers, recent years have seen a major growth of interest in both the neuroscience and psychology of curiosity. In this Perspective, we advocate for the importance of the field, provide a selective overview of its current state, and describe tasks that are used to study curiosity and information seeking. We propose that, rather than worry about defining curiosity, it is more helpful to consider the motivations for information-seeking behavior and to study it in its ethological context. PMID- 26539890 TI - Imaging Exocytosis of Single Synaptic Vesicles at a Fast CNS Presynaptic Terminal. AB - Synaptic vesicles are tethered to the active zone where they are docked/primed so that they can fuse rapidly upon Ca(2+) influx. To directly study these steps at a CNS presynaptic terminal, we used total internal reflection fluorescence (TIRF) microscopy at the live isolated calyx of Held terminal and measured the movements of single synaptic vesicle just beneath the plasma membrane. Only a subset of vesicles within the TIRF field underwent exocytosis. Following exocytosis, new vesicles (newcomers) approached the membrane and refilled the release sites slowly with a time constant of several seconds. Uniform elevation of the intracellular Ca(2+) using flash photolysis elicited an exocytotic burst followed by the sustained component, representing release of the readily releasable vesicles and vesicle replenishment, respectively. Surprisingly, newcomers were not released within a second of high Ca(2+). Instead, already-tethered vesicles became release-ready and mediated the replenishment. Our results reveal an important feature of conventional synapses. PMID- 26539889 TI - Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons. AB - During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory inhibitory balance essential for proper circuit function. Whether the class specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV(+) interneurons, suggesting that projection neuron class-specific identity can actively control the wiring of the cortical microcircuit. PMID- 26539892 TI - Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans. AB - Although Hox genes specify the differentiation of neuronal subtypes along the anterior-posterior axis, their mode of action is not entirely understood. Using two subtypes of the touch receptor neurons (TRNs) in C. elegans, we found that a "posterior induction" mechanism underlies the Hox control of terminal neuronal differentiation. The anterior subtype maintains a default TRN state, whereas the posterior subtype undergoes further morphological and transcriptional specification induced by the posterior Hox proteins, mainly EGL-5/Abd-B. Misexpression of the posterior Hox proteins transformed the anterior TRN subtype toward a posterior identity both morphologically and genetically. The specification of the posterior subtype requires EGL-5-induced repression of TALE cofactors, which antagonize EGL-5 functions, and the activation of rfip-1, a component of recycling endosomes, which mediates Hox activities by promoting subtype-specific neurite outgrowth. Finally, EGL-5 is required for subtype specific circuit formation by acting in both the sensory neuron and downstream interneuron to promote functional connectivity. PMID- 26539891 TI - Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. AB - Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID- 26539894 TI - Hippocampal Remapping after Partial Inactivation of the Medial Entorhinal Cortex. AB - Hippocampal place cells undergo remapping when the environment is changed. The mechanism of hippocampal remapping remains elusive but spatially modulated cells in the medial entorhinal cortex (MEC) have been identified as a possible contributor. Using pharmacogenetic and optogenetic approaches, we tested the role of MEC cells by examining in mice whether partial inactivation in MEC shifts hippocampal activity to a different subset of place cells with different receptive fields. The pharmacologically selective designer Gi-protein-coupled muscarinic receptor hM4D or the light-responsive microbial proton pump archaerhodopsin (ArchT) was expressed in MEC, and place cells were recorded after application of the inert ligand clozapine-N-oxide (CNO) or light at appropriate wavelengths. CNO or light caused partial inactivation of the MEC. The inactivation was followed by substantial remapping in the hippocampus, without disruption of the spatial firing properties of individual neurons. The results point to MEC input as an element of the mechanism for remapping in place cells. PMID- 26539895 TI - "Targeting" hepatitis C after liver transplantation. PMID- 26539893 TI - During Running in Place, Grid Cells Integrate Elapsed Time and Distance Run. AB - The spatial scale of grid cells may be provided by self-generated motion information or by external sensory information from environmental cues. To determine whether grid cell activity reflects distance traveled or elapsed time independent of external information, we recorded grid cells as animals ran in place on a treadmill. Grid cell activity was only weakly influenced by location, but most grid cells and other neurons recorded from the same electrodes strongly signaled a combination of distance and time, with some signaling only distance or time. Grid cells were more sharply tuned to time and distance than non-grid cells. Many grid cells exhibited multiple firing fields during treadmill running, parallel to the periodic firing fields observed in open fields, suggesting a common mode of information processing. These observations indicate that, in the absence of external dynamic cues, grid cells integrate self-generated distance and time information to encode a representation of experience. PMID- 26539897 TI - Salivary gland FNA: New markers and new opportunities for improved diagnosis. PMID- 26539896 TI - Evidence of altered matrix composition in iliac crest biopsies from patients with idiopathic juvenile osteoporosis. AB - PURPOSE: Idiopathic juvenile osteoporosis (IJO) is a rare condition in children, characterized by bone pain and long bone and vertebral fractures. Previously, IJO bone was solely characterized by histomorphometry and quantitative computed tomography. The goal of this study is to describe IJO bone composition. MATERIALS AND METHODS: Fourier transform infrared imaging (FTIRI), a vibrational spectroscopic technique providing spatially resolved images of chemical composition, was used to determine whether iliac crest biopsies from children with IJO differed in composition from and age- and sex-matched controls, and, as a secondary analysis, whether IJO bone showed the same disease dependent change in composition as do iliac crest bone biopsies from women with post-menopausal osteoporosis (PMO). Wilcoxon rank tests and linear regressions were used to analyze FTIRI variables (mineral-to-matrix ratio, carbonate-to-phosphate ratio, crystallinity, acid phosphate substitution, collagen maturity) and their individual pixel distributions (heterogeneity). RESULTS: Mineral-to-matrix ratio was comparable in IJO and age-matched controls. Contrastingly, collagen maturity (also known as collagen cross-link ratio) was higher in cortical and cancellous IJO bone compared with juvenile controls. Acid phosphate substitution was greater in IJO cancellous bone than in age-matched controls, suggesting IJO bone mineral is formed more recently, reflecting a slower mineralization process. This agrees with findings of increased heterogeneity for mineral-to-matrix and collagen maturity ratios in IJO cancellous bone. There were negative correlations between cancellous collagen maturity and previously reported histomorphometric bone formation markers. There were no correlations with indices of remodeling. CONCLUSIONS: IJO bone, similar to PMO bone, had elevated collagen maturity relative to its age-matched controls. This emphasizes the importance of the collagen matrix for bone health. IJO bone differed from PMO bone as IJO bone contains more recently formed mineral than age-matched controls but has a more mature matrix, whereas in PMO bone both mineral and matrix have older characteristics. PMID- 26539898 TI - Two new triterpenoids from Gypsophila oldhamiana. AB - Two new triterpenoids (1-2) were isolated and elucidated from the roots of Gypsophila oldhamiana, together with four known triterpenoids (3-6). Their structures were identified to be 3beta-hydroxyolean-13(18)-ene-23, 28-dioic acid (1), 3beta, 12alpha-dihydroxy-23-carboxyolean-28, 13beta-olide (2), 3beta, 16alpha-dihydroxy-23-oxoolean-13(18)-en-28-oic acid (3), gypsogenin (4), quillaic acid (5) and gypsogenic acid (6) by spectral methods. All compounds were tested for their cytotoxicities against human tumour cell lines (lung cancer H460 and gastric cancer SGC-7901) and for their antiangiogenic effects using a zebra fish model. All compounds showed interesting antiangiogenic activities and the significant cytotoxicities against H460. PMID- 26539899 TI - Condition-specific associations of symptoms of depression and anxiety in adolescents and young adults with asthma and food allergy. AB - OBJECTIVE: This study examined associations of asthma and food allergy with symptoms of depression and anxiety at 14 and 21 years of age to determine whether condition-specific associations exist. METHODS: Data come from 4972 adolescents in the Mater University Study of Pregnancy. Symptoms of depression and anxiety were assessed using the Youth Self-Report and Young Adult Self-Report. RESULTS: Condition-specific associations between asthma and depression, OR = 1.37 [1.12, 1.67] and between food allergy and anxiety, OR = 1.26 [1.04, 1.76] were found during adolescence, but not in young adulthood. Whereas asthma was associated with resolved depression, OR = 1.70 [1.13, 2.55], food allergy was associated with persistent anxiety, OR = 1.26 [1.01, 1.59]. CONCLUSIONS: In adolescents, asthma is associated with an increased risk of clinically relevant symptoms of depression and food allergy with an increased risk of clinically relevant symptoms of anxiety. Future research is needed to clarify directionality and mechanisms explaining these relationships. Health professionals should be aware of the increased risk of mental health problems in adolescents with asthma or food allergy. PMID- 26539900 TI - A Route for Phase Control in Metal Nanoparticles: A Potential Strategy to Create Advanced Materials. AB - There is untapped potential for materials whose crystal structures are unobtainable in the bulk state. Several examples of such structures have been found in nanomaterials, and these materials exhibit unique properties that arise from their unique electronic states and surface structures. Here, recent developments in the syntheses of these nanomaterials and their unique properties, such as hydrogen-storage ability and catalytic activity, are summarized. Firstly, the syntheses and properties of novel solid-solution alloy nanoparticles in immiscible alloy systems such as Ag-Rh and Pd-Ru are introduced. Following this, the crystal structure control of nanoscale Ru is discussed. These unique alloy materials show enhanced properties and highlight the potential of phase control to be a new strategy for nanomaterial development. PMID- 26539901 TI - The complete mitochondrial genome sequence of the ascomycete plant pathogen Colletotrichum acutatum. AB - Collectotrichum acutatum is a fungal plant pathogen that causes pre- and post harvest anthracnose on a wide range of plants worldwide. The complete mitochondrial genome of C. acutatum has been determined for the first time. This study revealed that the mitogenome of C. acutatum is a closed circular molecule of 30 892 bp in length, with a G + C content of 34.7%, which include 15 protein coding genes, 22 tRNA genes, and two rRNA genes. All the protein-coding genes, accounting for 46.6% of the C. acutatum mitogenome, start with the standard ATG codon and end with the TAA termination codon except for nad6 gene using the TAG termination codon. The mitogenome information of C. acutatum can provide molecular basis for further studies on molecular systematics and evolutionary dynamics. PMID- 26539902 TI - Growth of Staphylococcus aureus in Cooked Potato and Potato Salad--A One-Step Kinetic Analysis. AB - Staphylococcus aureus is a Gram-positive spherically-shaped bacterium capable of producing heat-stable enterotoxins that cause acute gastrointestinal diseases. The growth of this pathogen in food is a major threat to public health worldwide. Potato salad is a frequent vehicle for infection and food poisoning caused by S. aureus. Therefore, the objective of this study was to investigate the growth kinetics of S. aureus in cooked potato and potato salad. Samples of potato cubes and potato salad inoculated with S. aureus were incubated at temperatures between 8 and 43 degrees C to observe its growth for developing growth models. No growth was observed at 8 degrees C. The experimental results showed that the growth curves did not exhibit lag phases, and can be described by a 3-parameter logistic model. A one-step kinetic analysis approach was used to simultaneously analyze all growth curves by direct construction of both the primary and secondary (Ratkowsky square root) models using nonlinear regression to minimize the global residual error. The estimated nominal minimum growth temperature of S. aureus was 6.12 degrees C in potato cubes and 8.80 degrees C in potato salad. The estimated maximum growth temperatures of S. aureus in potato cubes and potato salad were very close to each other (46.3 and 46.8 degrees C, respectively). On the average, the specific growth rates of S. aureus in potato cubes were approximately 70% higher than those in potato salad. This study suggests that cooked potato and potato salad should be stored below 6 degrees C or above 47 degrees C to prevent the growth of S. aureus. The mathematical models and kinetic parameters can be used to accurately evaluate the effect of temperature abuse on the growth of S. aureus and conduct risk assessments of S. aureus in cooked potato and potato salad. PMID- 26539903 TI - Factors Associated With Increased Risk of Clubfoot: A Norwegian National Cohort Analysis. AB - BACKGROUND: Previous studies investigating the causes of clubfoot have shown conflicting results, potentially because of retrospective study designs or incomplete assessment of causative factors. The study aim was to examine risk factors for clubfoot in a large prospective Norwegian cohort. METHODS: Exposures prior and during pregnancy were identified through the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. This was linked to the Norwegian Medical Birth Registry, which provided clubfoot diagnosis through ICD-10 code Q66.0. Logistic regression analysis investigated associations between potential risk factors and development of clubfoot. RESULTS: A total of 121 clubfoot cases were identified; 1.1 per 1000 births. Parental diagnosis of clubfoot [odds ratio (OR): 31.5; 95% confidence interval (CI):9.61 103.3] and cigarette smoking, both in the three months prior to pregnancy (OR:1.82; 95%CI:1.05-3.18) and the first trimester (OR:2.67; 95% CI:1.28-5.55) were associated with clubfoot. Infants with clubfoot had greater solvent exposure (OR:1.66; 95% CI:1.00-2.76). Oligohydramnios, parental age, parental education, parity, maternal anxiety or depression, alcohol use, season of birth did not have statistically significant associations. CONCLUSIONS: In addition to parental diagnosis of clubfoot, results confirm the previously reported association between clubfoot and smoking, and counter previous evidence supporting season of birth, parental education, and other risk factors. Further studies are needed to investigate solvent exposure as a risk factor for clubfoot. Exposure to smoke and solvents can be controlled; this study highlights the importance of public health initiatives to limit these exposures both during pregnancy and in those considering conceiving in the future. PMID- 26539904 TI - Wernicke Encephalopathy and Sleeve Gastrectomy: A Case Report and Literature Review. AB - As the number of obese patients increases, as will the number of bariatric procedures. Malabsorptive bariatric procedures have emerged as one of common causes of Wernicke encephalopathy (WE), an acute neuropsychiatric disorder due to thiamine deficiency. However, restrictive procedures such as sleeve gastrectomy (SG) are less prone to cause nutrient deficiencies. WE occurred after SG is an uncommon complication because the main absorptive sites for thiamine are intact after SG. Here, we report a case of WE after SG. With rapid increase in the use of SG for morbid obesity, this case deserves particular attention from clinicians. PMID- 26539905 TI - Breastfed Infants Exposed to Combined Antipsychotics: Two Case Reports. AB - Manic episodes of bipolar disorder and psychotic exacerbations of schizophrenia, for which the antipsychotic drugs are most commonly prescribed, are frequently seen in the postpartum period. Despite the existence of single use of antipsychotics, data on safety of combined antipsychotics on the breastfed infants are limited. This report presents the clinical outcome of 2 infants exposed to combined antipsychotic during the lactation period. PMID- 26539906 TI - Drug-Induced Subacute Cutaneous Lupus Erythematosus in a Patient Receiving Therapy for Chronic Hepatitis C. AB - Hepatitis C infection and its treatment have been associated with extrahepatic manifestations, including different skin conditions. Over the past decades, a greater number of drugs have been implicated as triggers for drug-induced subacute cutaneous lupus erythematosus. We report a case of a 42-year-old Hispanic man who developed a forehead violaceous rash during treatment with pegylated interferon alpha-2a as part of his therapy against hepatitis C infection that subsequently resulted to be subacute cutaneous lupus erythematosus. The skin lesion improved with discontinuation of medication and some topic therapy. PMID- 26539907 TI - Zolpidem Overdose: A Medical and Ethical Dilemma. AB - Acute altered mental status can be caused by a broad range of etiologies, including cerebrovascular, neurologic, traumatic, metabolic, infectious, psychiatric, medications, etc. We present a case of a 53-year-old healthcare professional with an acute altered mental status after a trip to Africa. The patient was extensively worked up for infectious, cardiovascular, and neurologic etiologies, and all results were within normal limits. Further history revealed an overdose of a self-medicated hypnotic (zolpidem) for insomnia. The patient was conservatively managed and discharged on trazadone for insomnia. PMID- 26539908 TI - Perspectives on the Guidelines of the American Thyroid Association. PMID- 26539910 TI - Cracking the code of neuronal apoptosis and survival. AB - Neuronal apoptosis and survival are tightly controlled processes that regulate cell fate during the development of the central nervous system and its homeostasis throughout adulthood. A new study in primary cultures of cerebellar granule neurons identified common transcriptional cascades during rescue from apoptosis by insulin-like growth factor-1 (Igf1) and pituitary adenylyl cyclase activating polypeptide (Pacap), thus suggesting the existence of a high degree of conservation of cell survival pathways. PMID- 26539909 TI - Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation. AB - Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1 C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis. PMID- 26539911 TI - Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53. AB - Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy. PMID- 26539912 TI - L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer's disease via activating dopamine D1 receptor/PKA signaling pathway. AB - It is accepted that amyloid beta-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting alpha-amino-3 hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway. PMID- 26539913 TI - The point mutation UCH-L1 C152A protects primary neurons against cyclopentenone prostaglandin-induced cytotoxicity: implications for post-ischemic neuronal injury. AB - Cyclopentenone prostaglandins (CyPGs), such as 15-deoxy-Delta(12,14) prostaglandin J2 (15dPGJ2), are reactive prostaglandin metabolites exerting a variety of biological effects. CyPGs are produced in ischemic brain and disrupt the ubiquitin-proteasome system (UPS). Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a brain-specific deubiquitinating enzyme that has been linked to neurodegenerative diseases. Using tandem mass spectrometry (MS) analyses, we found that the C152 site of UCH-L1 is adducted by CyPGs. Mutation of C152 to alanine (C152A) inhibited CyPG modification and conserved recombinant UCH-L1 protein hydrolase activity after 15dPGJ2 treatment. A knock-in (KI) mouse expressing the UCH-L1 C152A mutation was constructed with the bacterial artificial chromosome (BAC) technique. Brain expression and distribution of UCH L1 in the KI mouse was similar to that of wild type (WT) as determined by western blotting. Primary cortical neurons derived from KI mice were resistant to 15dPGJ2 cytotoxicity compared with neurons from WT mice as detected by the WST-1 cell viability assay and caspase-3 and poly ADP ribose polymerase (PARP) cleavage. This protective effect was accompanied with significantly less ubiquitinated protein accumulation and aggregation as well as less UCH-L1 aggregation in C152A KI primary neurons after 15dPGJ2 treatment. Additionally, 15dPGJ2-induced axonal injury was also significantly attenuated in KI neurons as compared with WT. Taken together, these studies indicate that UCH-L1 function is important in hypoxic neuronal death, and the C152 site of UCH-L1 has a significant role in neuronal survival after hypoxic/ischemic injury. PMID- 26539915 TI - The esoteric roles of Bcl-2 family proteins in glucose homeostasis and cell survival. PMID- 26539914 TI - Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke. AB - Previous studies show that caspase-6 and caspase-8 are involved in neuronal apoptosis and regenerative failure after trauma of the adult central nervous system (CNS). In this study, we evaluated whether caspase-6 or -8 inhibitors can reduce cerebral or retinal injury after ischemia. Cerebral infarct volume, relative to appropriate controls, was significantly reduced in groups treated with caspase-6 or -8 inhibitors. Concomitantly, these treatments also reduced neurological deficits, reduced edema, increased cell proliferation, and increased neurofilament levels in the injured cerebrum. Caspase-6 and -8 inhibitors, or siRNAs, also increased retinal ganglion cell survival at 14 days after ischemic injury. Caspase-6 or -8 inhibition also decreased caspase-3, -6, and caspase-8 cleavage when assayed by western blot and reduced caspase-3 and -6 activities in colorimetric assays. We have shown that caspase-6 or caspase-8 inhibition decreases the neuropathological consequences of cerebral or retinal infarction, thereby emphasizing their importance in ischemic neuronal degeneration. As such, caspase-6 and -8 are potential targets for future therapies aimed at attenuating the devastating functional losses that result from retinal or cerebral stroke. PMID- 26539918 TI - Portable Monitoring for the Diagnosis of OSA. AB - In-laboratory, attended polysomnography has long been the gold standard for the diagnosis of sleep-disordered breathing (SDB). In recent years, economic pressures and long wait times have driven interest in home sleep testing, which has, in turn, led to the development of algorithms that bypass the sleep laboratory in favor of portable monitoring studies and in-home initiation of positive airway pressure therapy. For appropriately selected outpatients, evidence is accumulating that portable monitors are a reasonable substitute for in-laboratory polysomnography. In the inpatient setting, in which SDB is both highly prevalent and associated with adverse outcomes in certain populations, the literature is evolving on the use of portable monitors to expedite diagnosis and treatment of SDB. This review discusses society guidelines and recent research in the growing field of portable monitoring. PMID- 26539916 TI - Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents. AB - Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy. PMID- 26539917 TI - Mahogunin regulates fusion between amphisomes/MVBs and lysosomes via ubiquitination of TSG101. AB - Aberrant metabolic forms of the prion protein (PrP), membrane-associated (Ctm)PrP and cytosolic (cyPrP) interact with the cytosolic ubiquitin E3 ligase, Mahogunin Ring Finger-1 (MGRN1) and affect lysosomes. MGRN1 also interacts with and ubiquitinates TSG101, an ESCRT-I protein, involved in endocytosis. We report that MGRN1 modulates macroautophagy. In cultured cells, functional depletion of MGRN1 or overexpression of (Ctm)PrP and cyPrP blocks autophagosome-lysosome fusion, alleviates the autophagic flux and its degradative competence. Concurrently, the degradation of cargo from the endo-lysosomal pathway is also affected. This is significant because catalytic inactivation of MGRN1 alleviates fusion of lysosomes with either autophagosomes (via amphisomes) or late endosomes (either direct or mediated through amphisomes), without drastically perturbing maturation of late endosomes, generation of amphisomes or lysosomal proteolytic activity. The compromised lysosomal fusion events are rescued by overexpression of TSG101 and/or its monoubiquitination in the presence of MGRN1. Thus, for the first time we elucidate that MGRN1 simultaneously modulates both autophagy and heterophagy via ubiquitin-mediated post-translational modification of TSG101. PMID- 26539919 TI - Improving acute kidney injury diagnostics using predictive analytics. AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) is a multifactorial syndrome affecting an alarming proportion of hospitalized patients. Although early recognition may expedite management, the ability to identify patients at-risk and those suffering real-time injury is inconsistent. The review will summarize the recent reports describing advancements in the area of AKI epidemiology, specifically focusing on risk scoring and predictive analytics. RECENT FINDINGS: In the critical care population, the primary underlying factors limiting prediction models include an inability to properly account for patient heterogeneity and underperforming metrics used to assess kidney function. Severity of illness scores demonstrate limited AKI predictive performance. Recent evidence suggests traditional methods for detecting AKI may be leveraged and ultimately replaced by newer, more sophisticated analytical tools capable of prediction and identification: risk stratification, novel AKI biomarkers, and clinical information systems. Additionally, the utility of novel biomarkers may be optimized through targeting using patient context, and may provide more granular information about the injury phenotype. Finally, manipulation of the electronic health record allows for real-time recognition of injury. SUMMARY: Integrating a high-functioning clinical information system with risk stratification methodology and novel biomarker yields a predictive analytic model for AKI diagnostics. PMID- 26539920 TI - Recent developments in electronic alerts for acute kidney injury. AB - PURPOSE OF REVIEW: Efforts to improve outcomes from acute kidney injury (AKI) have focussed on timely diagnosis and effective delivery of basic patient care. Electronic alerts (e-alerts) for AKI have attracted interest as a tool to facilitate this. Initial feasibility has already been demonstrated; this review will discuss recent advances in alert methodology, implementation beyond single centres and reported effect on outcomes. RECENT FINDINGS: On-going descriptions of e-alerts highlight increasing variation in both detection algorithms and alert processes. In England, this is being addressed by national rollout of a standardized detection algorithm; recent data have shown this to have good diagnostic performance. In critical care, fully automated detection systems incorporating both serum creatinine and urine output criteria have been developed. A recent randomized trial of e-alerts has also been reported, in which isolated use of a text message e-alert did not affect either clinician behaviour or patient outcome. SUMMARY: As e-alerts gain popularity, consideration must be given to both the method of AKI detection and the method by which results are communicated to end-users; these aspects influence the degree of these systems' effectiveness. This approach should be coupled to further work to study the effect on patient outcomes of those interventions that have been demonstrated to influence clinician behaviour. PMID- 26539921 TI - Automated/integrated real-time clinical decision support in acute kidney injury. AB - PURPOSE OF REVIEW: Health information technology advancements have resulted in recent increased sophistication of the electronic health record, whereby patient demographic, physiological, and laboratory data can be extracted real-time and integrated into clinical decision support (CDS). RECENT FINDINGS: The implementation of health information technology advancements into CDS in the renal realm has been focused mainly on assessment of kidney function to guide medication dosing in the setting of reduced function or to reactively detect acute kidney injury (AKI) heralded by an abrupt increase in serum creatinine. More recent work has combined risk stratification algorithms to guide proactive diagnostic or therapeutic intervention to prevent AKI or reduce its severity. SUMMARY: Early, real-time identification and notification to healthcare providers of patients at risk for, or with, acute or chronic kidney disease can drive simple interventions to reduce harm. Similarly, screening patients at risk for AKI with these platforms to alert research personnel will lead to improve study subject recruitment. However, sole reliance on electronic health record generated alerts without active healthcare team integration and assessment represents a major barrier to the realization of the potential of CDS to improve healthcare quality and outcomes. PMID- 26539922 TI - Quality measures for acute kidney injury and continuous renal replacement therapy. AB - PURPOSE OF REVIEW: Quality and safety are important priorities in the care of critically ill patients. For patients with acute kidney injury (AKI) or for those receiving continuous renal replacement therapy (CRRT), measures and outcomes associated with quality of care have been suboptimally developed and evaluated. The review is timely as it summarizes current quality practices in AKI and CRRT, and presents ongoing and future developments. RECENT FINDINGS: The review begins with the history of quality and safety in healthcare. We then discuss the current quality of care offered in AKI and CRRT. Quality measure development methodology, such as plan-do-study-act and the focus-analyze-describe-execute models and lean thinking are then presented and discussed. Finally, recent evidence for quality in AKI and CRRT care, including proposed quality measures, are discussed. SUMMARY: Few studies have examined the quality of care provided to patients with AKI and CRRT. Evidence suggests opportunities to improve the quality of care received by patients at risk of or who have developed AKI. Priorities for improving quality of care exist across several important themes including risk identification, diagnosis, monitoring, investigation, and strategies for management. Similarly, evidence-informed quality measures of CRRT care have not been rigorously evaluated. These are important knowledge-to-care gaps that require further investigation. PMID- 26539923 TI - Improving outcomes of acute kidney injury survivors. AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) is a common problem in critically ill patients, with long-term health implications that extend beyond hospital discharge. Though they are at a high risk of adverse events, AKI survivors may not be receiving adequate postdischarge medical attention. This review discusses recently published data regarding health outcomes after AKI, the current state of post-AKI care, and potential opportunities to improve outpatient care after AKI. RECENT FINDINGS: In addition to predisposing to de-novo chronic kidney disease or an exacerbation of previously existing chronic kidney disease, a prior episode of AKI has been linked to subsequent cardiac events, cerebrovascular events, and the need for hospital readmission. Despite this, a population-wide study in Ontario showed that only 40% of patients surviving an episode of dialysis-requiring AKI visited a nephrologist within 90 days of hospital discharge. This care gap is important since outpatient contact with a nephrologist during this critical period was associated with enhanced survival. SUMMARY: AKI is associated with a number of long-term health effects, and new strategies may be needed to address this emerging public health issue. An ambulatory program dedicated to the postdischarge care of AKI survivors may confer a variety of benefits. Future research is needed to evaluate this model of care. PMID- 26539924 TI - Traumatic brain injury advancements. AB - PURPOSE OF REVIEW: Traumatic brain injury (TBI) remains the leading cause of morbidity and mortality in the United States. Over the last decade, several advancements have been made in the field of TBI all aimed at improving outcomes. RECENT FINDINGS: Advancements in the management of TBI have been made possible through improved understanding of basic pathophysiology associated with this condition. The aim of this review is to briefly highlight the underlying pathophysiology of TBI and the most recent advancements and novel strategies being used in its treatment. We also briefly discuss coagulopathy of TBI, clinical management of TBI and how it has evolved recently. SUMMARY: The mortality associated with TBI continues to remain high and several novel strategies have emerged as potential candidates for the treatment of secondary brain injury. The clinical management of TBI and associated coagulopathy has evolved allowing for a more tailored approach toward its management. PMID- 26539925 TI - Geriatric trauma. AB - PURPOSE OF REVIEW: The landscape of trauma is changing due to an aging population. Geriatric patients represent an increasing number and proportion of trauma admissions and deaths. This review explores recent literature on geriatric trauma, including triage criteria, assessment of frailty, fall-related injury, treatment of head injury complicated by coagulopathy, goals of care, and the need for ongoing education of all surgeons in the care of the elderly. RECENT FINDINGS: Early identification of high-risk geriatric patients is imperative to initiate early resuscitative efforts. Geriatric patients are typically undertriaged because of their baseline frailty being underappreciated; however, centers that see more geriatric patients do better. Rapid reversal of anticoagulation is important in preventing progression of brain injury. Anticipation of difficult disposition necessitates early involvement of physical therapy for rehabilitation and case management for appropriate placement. SUMMARY: Optimal care of geriatric trauma patients will be based on the well established tenets of trauma resuscitation and injury repair, but with distinct elements that address the physiological and anatomical challenges presented by geriatric patients. PMID- 26539926 TI - Nutritional controversies in critical care: revisiting enteral glutamine during critical illness and injury. AB - PURPOSE OF REVIEW: This article examines some of the articles that inspired recent changes to critical care guidelines related to glutamine in enteral nutrition. RECENT FINDINGS: Two recent multicenter randomized controlled trials involving enteral glutamine have reported increased mortality rates in groups of mechanically ventilated adult patients, while demonstrating no additional benefits to other outcomes, such as nosocomial infections. SUMMARY: Recent studies suggest that enteral glutamine supplementation may not provide significant clinical benefits to adult patients on mechanical ventilation with multiple organ failure, but more information is still needed when attempting to apply these results to other groups of critical care patients. PMID- 26539927 TI - Damage control surgery. AB - PURPOSE OF REVIEW: Damage control surgery (DCS) has become a lifesaving maneuver for critically injured patients when utilized in appropriate scenarios. Despite this reality, indications for initiating DCS remain debated. RECENT FINDINGS: Despite discussion surrounding the appropriate indications for DCS, this series of fundamental principles includes a rapidly abbreviated operative intervention aimed at arresting ongoing hemorrhage and containing gastrointestinal contamination in a patient approaching physiologic exhaustion, which includes both vascular and nonvascular damage control techniques, in addition to management of the open abdomen. Patients are then returned to the operating theater for definitive reconstruction once their physiology has been stabilized within the ICU. SUMMARY: DCS is lifesaving when applied in appropriate clinical scenarios involving critically injured patients. Overuse of this technique can lead to increased patient morbidity and cost however. PMID- 26539928 TI - Blunt thoracic trauma: recent advances and outstanding questions. AB - PURPOSE OF REVIEW: The treatment of blunt thoracic injuries is complex and evolving. The aim of this review is to focus on what is new with ventilation for blunt chest trauma as well as an update on the current management strategies for blunt aortic injury and rib fractures. RECENT FINDINGS: Early use of noninvasive ventilation appears to be well tolerated in select hemodynamically stable blunt trauma patients. For those patients requiring intubation, airway pressure release ventilation is an excellent mode to decrease the risk of posttraumatic acute lung injury. Endovascular repair of blunt thoracic aortic injuries provides benefit over open repair and, if possible, delayed repair confers a mortality advantage. Despite its increasing use, there continue to be conflicting results about the role of surgical rib fixation for the treatment of flail chest. SUMMARY: Blunt thoracic injuries are commonly treated in the ICU and a solid knowledge of mechanical ventilation strategies (both noninvasive and invasive) is essential. Blunt thoracic aortic injuries require early diagnosis and aggressive blood pressure management. Not all such injuries need operative repair but those that do benefit from an endovascular approach. The management of flail chest includes early aggressive multimodal analgesia, adequate oxygen, and ventilatory support. Surgical rib fixation should be considered in select patients. PMID- 26539929 TI - Acute kidney injury in hematological patients. AB - PURPOSE OF REVIEW: The present article reviews the recent literature on the main aspects of acute kidney injury (AKI) developing in patients with hematological malignancies admitted to ICU. RECENT FINDINGS: Up to two thirds of critically ill patients with hematological malignancies develop AKI. Current mortality rates range from 40 to 60% for most patients with hematological malignancies, except for recipients of allogeneic hematopoietic stem cell transplantation in whom outcomes remain very poor. Renal function recovery occurs in most patients with AKI, but is dependent on the underlying causes. AKI is usually multifactorial, resulting from causes common to other ICU patients and related to the underlying malignancy or its treatment. New targeted therapies and treatment strategies are potentially associated with AKI. Management of these patients requires a high degree of suspicion, close monitoring of metabolic parameters, and use of preventive strategies to limit risk of AKI or to mitigate its severity. SUMMARY: AKI is a frequent and severe complication in critically ill patients with hematological malignancies. As the clinical management is complex, close collaboration with hematologists is paramount. PMID- 26539930 TI - Urgent chemotherapy in hematological patients in the ICU. AB - PURPOSE OF REVIEW: Over the past decades, survival of critically ill hematological patients has dramatically improved, and these patients are more frequently referred to the ICU for intensive treatment, including a rising need for administering anticancer-therapy in this setting. RECENT FINDINGS: The scarce literature on this subject provides evidence for feasibility of administering chemotherapy in the ICU, with expected ICU survival of 60-70%, and one in three patients surviving at least 1 year after discharge. We summarize the recent evidence concerning outcome, dosing and indications of chemotherapy in the ICU, and provide practical guidelines for some special oncological situations. SUMMARY: Anticancer-therapy in the ICU is feasible and no longer futile as long as it is initiated in a selected, well-informed patient population with reasonable prognostic expectations. Accurate recognition of organ failure and early referral to the ICU for both supportive care and timely administration of chemotherapy is recommended before the development of multisystem organ failure. PMID- 26539931 TI - Sickle cell disease in the ICU. AB - PURPOSE OF REVIEW: The review focuses on severe acute vaso-occlusive manifestations of sickle cell disease leading adult patients to the ICU. RECENT FINDINGS: Careful consideration should be paid to look for pulmonary vascular dysfunction and acute kidney injury, because of their prognostic role during acute vaso-occlusive manifestations. Alloimmunization and delayed haemolytic transfusion reactions are emerging complications that should be thought to be diagnosed, as they may imply a conservative management. The life-threatening complication raises the question about the indications of blood transfusion therapy for acute sickle cell disease complications, no randomized controlled trials being available to assess the role of blood transfusion in the acute setting. SUMMARY: Acute vaso-occlusive episodes are characterized by an unpredictable course that needs for vigilance for everyone, and justifies ICU or intermediate care unit admission to allow close monitoring, and supportive treatment in a timely fashion. PMID- 26539932 TI - Heparin-induced thrombocytopenia. AB - PURPOSE OF REVIEW: Thrombocytopenia and heparin exposure are common in critically ill patients, yet immune heparin-induced thrombocytopenia (HIT), a prothrombotic adverse effect of heparin, rarely accounts for thrombocytopenia in this patient population. The review discusses the clinical and laboratory features that distinguish HIT from non-HIT thrombocytopenia. RECENT FINDINGS: The frequency of HIT in heparin-exposed critically ill patients is approximately 0.3-0.5% versus at least a 30-50% background frequency of non-HIT thrombocytopenia. Most patients who form anti-PF4/heparin antibodies do not develop HIT, contributing to HIT overdiagnosis. Disseminated intravascular coagulation (DIC), particularly in the setting of cardiogenic or septic shock associated with 'shock liver', can cause ischemic limb gangrene with pulses, mimicking a clinical picture of HIT. However, whereas non-HIT-related DIC with microthrombosis can be treated with heparin, HIT usually requires nonheparin anticoagulation. HIT-associated DIC can result in an elevated INR, which could reflect factor VII depletion because of extrinsic (tissue factor) pathway-mediated activation of coagulation. SUMMARY: Greater understanding of the various clinical and laboratory features that distinguish HIT from non-HIT thrombocytopenia could help improve outcomes in patients who develop thrombocytopenia and coagulopathies in the ICU. PMID- 26539933 TI - Severe infections in neutropenic patients. AB - PURPOSE OF REVIEW: Severe infections in neutropenic patients can rapidly progress to septic shock and multiorgan failure with a high associated mortality. In this article we discuss current practice, emerging trends and controversies, including the prophylactic and empiric use of antimicrobial therapy, and advances in cellular and immunotherapy. RECENT FINDINGS: Neutropenia is no longer a consistent factor predicting poor outcome in haematological patients admitted to the ICU. Severe infections in neutropenic patients are often polymicrobial, and pathogen resistance remains a challenge. Invasive fungal infection is still predictive of poor outcome. There has been a rapid expansion in the diagnostics and treatment modalities available for patients with invasive fungal infection. Use of growth factors, polyvalent immunoglobulin, and cellular therapy appear to be of value in certain groups of patients. There is a move away from the use of noninvasive ventilation and the use of high-flow nasal oxygen therapy is one of a number of novel respiratory support strategies that is yet to be evaluated in this patient population. SUMMARY: Translation of current advances in antimicrobial, cellular and immunotherapy, and diagnostics to aid clinical management by the bedside is important in reducing morbidity and mortality for neutropenic patients with severe infection. PMID- 26539935 TI - Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design. AB - We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50 degrees C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances. PMID- 26539936 TI - Temporal Trends in Postmastectomy Radiation Therapy and Breast Reconstruction Associated With Changes in National Comprehensive Cancer Network Guidelines. AB - IMPORTANCE: Evolving data on the effectiveness of postmastectomy radiation therapy (PMRT) have led to changes in National Comprehensive Cancer Network (NCCN) recommendations, counseling clinicians to "strongly consider" PMRT for patients with breast cancer with tumors 5 cm or smaller and 1 to 3 positive nodes; however, anticipation of PMRT may lead to delay or omission of reconstruction, which can have cosmetic, quality-of-life, and complication implications for patients. OBJECTIVE: To determine whether revised guidelines have increased PMRT and affected receipt of breast reconstruction. We hypothesized that (1) PMRT rates would increase for women affected by the revised guidelines while remaining stable in other cohorts and (2) receipt of breast reconstruction would decrease in these women while increasing in other groups. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based cohort study of Surveillance, Epidemiology, and End Results (SEER) data on women with stage I to III breast cancer undergoing mastectomy from 2000 through 2011. Our analytic sample (N = 62,442) was divided into cohorts on the basis of current NCCN radiotherapy recommendations: "radiotherapy recommended" (tumors > 5 cm or >= 4 positive lymph nodes), "strongly consider radiotherapy" (tumor <= 5 cm, 1-3 positive nodes), and "radiotherapy not recommended" (tumors <= 5 cm, no positive nodes). MAIN OUTCOMES AND MEASURES: We used Joinpoint regression analysis to evaluate temporal trends in receipt of PMRT and breast reconstruction. RESULTS: The 3 cohorts comprised 15,999 in the "radiotherapy recommended" group, 15,006 in the "strongly consider radiotherapy" group, and 31,837 in the "radiotherapy not recommended" group. [corrected]. Rates of PMRT were unchanged in the radiotherapy recommended (29.9%) and radiotherapy not recommended (7.4%) cohorts over the study period. Receipt of PMRT for the strongly consider radiotherapy cohort was unchanged at 26.9% until 2007. At that time, a significant change in the APC was observed (P = .01) with an increase in APC from 2.1% to 9.0% (P = .02) through the end of the study period, for a final rate of 40.5%. Breast reconstruction increased across all cohorts. Despite increasing receipt of PMRT, the strongly consider radiotherapy cohort maintained a consistent increase in reconstruction (annual percentage change, 7.4%) throughout the study period. This is similar to the increase in reconstruction observed for the radiotherapy recommended (10.7%) and radiotherapy not recommended (8.4%) cohorts. CONCLUSIONS AND RELEVANCE: Changes in NCCN guidelines have been associated with an increase in PMRT among patients with tumors 5 cm or smaller and 1 to 3 positive nodes without an associated decrease in receipt of reconstruction. This may represent increasing clinician comfort with irradiating a new breast reconstruction and may have cosmetic and quality-of-life implications for patients. PMID- 26539937 TI - Surgery for lymph node metastases of medullary thyroid carcinoma: A review. AB - Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease. PMID- 26539938 TI - Primary and Revision Posterior Lumbar Fusion Have Similar Short-Term Complication Rates. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare short-term morbidity for primary and revision posterior lumbar fusions. SUMMARY OF BACKGROUND DATA: Revision lumbar fusions are unfortunately relatively common. Previous studies have described an increased risk of postoperative complications after revision lumbar fusion; however, these studies have been limited by small sample sizes, poor data quality, and/or narrow outcome measures. There is a need to validate these findings using a high-quality, national cohort of patients to have an accurate assessment of the relative risk of revision posterior lumbar fusions compared with primary lumbar fusion. METHODS: The prospectively-collected American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients that underwent undergoing primary and revision posterior lumbar fusion from 2005 to 2013. The occurrence of individual and aggregated postoperative complications within 30 days, along with rates of blood transfusion and readmission, were compared between primary and revision procedures using bivariate and multivariate Poisson regression with robust error variance to control for patient and operative characteristics. Operative time and postoperative length of stay were compared between groups using bivariate and multivariate linear regression. RESULTS: Of the 14,873 posterior lumbar fusion procedures that met inclusion criteria, 1287 (8.7%) were revision cases. There were no differences in the rates of 30-day postoperative complications or readmission between primary and revision posterior lumbar fusion using multivariate analysis to control for patient and operative characteristics. Similarly, no significant differences were found for operative time or postoperative length of stay. There was an increased rate of blood transfusion for revision surgery compared with primary surgery (relative risk 1.4, P < 0.001). CONCLUSION: This study suggests that revision posterior lumbar fusion does not carry significantly increased risk of complications or readmission compared with a primary posterior lumbar fusion. Patients undergoing revision surgery were more likely to receive a blood transfusion. This information suggests that general health risk stratification for revision procedures can be similar to that considered for primary cases. LEVEL OF EVIDENCE: 3. PMID- 26539939 TI - Implementing High-Value Care. AB - OBJECTIVES: Our objectives were to assess physician knowledge of costs of products, tests, and services commonly used by obstetrician/gynecologists (OB/GYNs) and identify those items that could be eliminated without decreasing quality of care by performing a prospective observational pilot study. METHODS: An anonymous electronic survey was distributed to 70 OB/GYN providers at Greenville Memorial Hospital. Survey items included common laboratory tests, medications, and clinical services. The survey was used to identify items with high cost for which there were less costly but equally efficacious alternatives. As an educational intervention, grand rounds reviewing the survey results, as well as recommendations that would allow for lean healthcare changes, were conducted. Utilization and cost savings were tracked for a 1-year preintervention and a 1-year postintervention. RESULTS: In total, 50 of 70 providers (71%) completed the survey. Hydrocortisone acetate/pramoxine hydrochloride and dinoprostone vaginal inserts were targeted for intervention. Use of the dinoprostone vaginal insert decreased 50.5% with a savings of $66,500 when comparing the preintervention period with the postintervention period. Use of hydrocortisone acetate/pramoxine hydrochloride decreased 90% with a savings of $92,655. Combined, the decreased use of these products led to a $159,155 cost savings in the 1-year postintervention period. CONCLUSIONS: OB/GYN providers at our institution had a poor working knowledge of costs. Through the use of a survey and educational intervention, we demonstrated that simple interventions could lead to high-quality, lean healthcare changes. PMID- 26539940 TI - Commentary on "Implementing High-Value Care". PMID- 26539941 TI - State Health Mapper: An Interactive, Web-Based Tool for Physician Workforce Planning, Recruitment, and Health Services Research. AB - OBJECTIVES: Health rankings in Mississippi are abysmal. Mississippi also has fewer physicians to serve its population compared with all other states. Many residents of this predominately rural state do not have access to healthcare providers. To better understand the demographics and distribution of the current health workforce in Mississippi, the main objective of the study was to design a Web-based, spatial, interactive application to visualize and explore the physician workforce. METHODS: A Web application was designed to assist in health workforce planning. Secondary datasets of licensure and population information were obtained, and live feeds from licensure systems are being established. Several technologies were used to develop an intuitive, user-friendly application. Custom programming was completed in JavaScript so the application could run on most platforms, including mobile devices. RESULTS: The application allows users to identify and query geographic locations of individual or aggregated physicians based on attributes included in the licensure data, to perform drive time or buffer analyses, and to explore sociodemographic population data by geographic area of choice. This Web-based application with analytical tools visually represents the physician workforce licensed in Mississippi and its attributes, and provides access to much-needed information for statewide health workforce planning and research. CONCLUSIONS: The success of the application is not only based on the practicality of the tool but also on its ease of use. Feedback has been positive and has come from a wide variety of organizations across the state. PMID- 26539942 TI - House Calls: Physicians in the US Congress, 2005-2015. AB - OBJECTIVES: Physicians occupy a prominent position in the US healthcare system, and physicians who serve in Congress may bring a particular perspective, expertise, and influence to health-related legislation. The purpose of this study was to describe physician membership in the US Congress between 2005 and 2015. METHODS: Congressional biographical records were searched to identify physicians who served in the US Congress from 2005 to 2015. Political and demographic characteristics of physician-members were compared with those of nonphysician members of Congress and of all US physicians. The numbers of physicians in recent Congresses also were compared with those in each Congress since 1945. RESULTS: A total of 27 physicians representing 17 states have served in Congress since 2005. There has been a significant increase in physician representation since 1987, reaching a high of 20 members (3.7%) in the Congresses immediately following passage of the Patient Protection and Affordable Care Act. Physician-members were mostly men (93%) and more likely than their Congressional colleagues to be Republican (78% vs 53% of all members, P = 0.007) and from the South (63% vs 35% of all members, P = 0.003). Compared with physicians in general, physicians in Congress were more likely to be men (93% vs 70%, P = 0.009) and surgeons (26% vs 11%, P = 0.01). CONCLUSIONS: Physician representation in Congress has increased substantially since 2000, potentially reflecting the greater political prominence of healthcare issues, as well as increased interest by and recruitment of physician-candidates. Physicians in Congress differ from their colleagues and from physicians in general in various demographic and political characteristics. PMID- 26539943 TI - Commentary on "House Calls: Physicians in the US Congress, 2005-2015". PMID- 26539944 TI - Plane-Assisted Suicide. PMID- 26539945 TI - Association of Systemic Inflammatory Response Syndrome with Clinical Outcomes of Pediatric Patients with Pneumonia. AB - OBJECTIVES: Systemic inflammatory response syndrome (SIRS) may complicate pneumonia. When present, it suggests that the patient's pneumonia is more severe. As such, recognition of SIRS among patients with pneumonia may be helpful in identifying those requiring more careful evaluation. Our objective was to examine the relation between the presence of SIRS and adverse clinical outcomes among children with pneumonia seen in the emergency department (ED). METHODS: A retrospective chart review was performed on children diagnosed as having community-acquired pneumonia who presented to a children's hospital ED during a 3 month period. SIRS was determined by using a modification of the International Consensus Conference on Pediatric Sepsis criteria. Specifically, the SIRS criteria require an abnormal temperature-corrected heart rate or respiratory rate and either an abnormal temperature or white blood cell count. The threshold for abnormal vital signs and white blood cell counts used to determine SIRS was adjusted based on the patient's age. Morbidity endpoints included progression to inpatient or observation status or subsequent return to the ED for pneumonia, need for video-assisted thoracoscopic surgery, and total hospital length of stay as measured from ED triage assessment to final discharge from the hospital (ED, observation, or inpatient), and the need for mechanical ventilation. RESULTS: A total of 276 children were included in the analysis. Pneumonia patients with SIRS (n = 38) had a greater rate of hospital admission or ED return compared with SIRS negative patients (n = 238; 79% vs 34.5%, respectively; P < 0.0001). Children with SIRS-positive pneumonia were at greater risk of requiring video-assisted thoracoscopic surgery (18.4% vs 0.8%; P < 0.0001). In addition, pneumonia patients with SIRS had a significantly longer median length of stay compared with pneumonia patients without SIRS (2.7 vs 0.19 days, P < 0.0001) and also had a significantly higher risk of mechanical ventilation (10.5% vs 0.8%). CONCLUSIONS: SIRS in children with community-acquired pneumonia is associated with a significantly higher likelihood of experiencing a more adverse outcome. Based on these observations, a sepsis screening tool in the ED that identifies SIRS in children with pneumonia has the potential to identify those children needing more intense monitoring and treatment. PMID- 26539946 TI - The South Carolina HIV Cascade of Care. AB - OBJECTIVES: In recent years, the human immunodeficiency virus (HIV) cascade of care describing the spectrum of engagement in HIV care from diagnosis to virologic suppression has been used widely in determining the progress and success in public health efforts to control the HIV epidemic. For more than a decade South Carolina consistently ranked among the top10 states in the United States with the highest acquired immunodeficiency syndrome case rates, suggesting late diagnoses and issues with retention in care. The primary objective of this study was to develop an HIV cascade of care for the state that may help identify opportunities for appropriate future interventions. METHODS: The South Carolina Enhanced HIV/AIDS Reporting System database was used to develop the HIV cascade of care indicating the percentages of the diagnosed individuals who were linked to care, received any care, were retained in care, and achieved virologic suppression using standardized metrics recommended by the Centers for Disease Control and Prevention. The sample included all individuals in South Carolina who were diagnosed as having HIV by December 31, 2011 and who were alive at the end of 2012. RESULTS: Of the 14,523 South Carolinians living with HIV at the end of 2012, 64% had received any HIV care, 53% were retained in care, and 48% were virologically suppressed during 2012. CONCLUSIONS: This is the first HIV cascade of care model for South Carolina. Efforts are needed to improve public health initiatives to link, engage, and retain individuals with HIV in care. PMID- 26539947 TI - Author Degrees in Medical Publishing: Choice or Convenience? PMID- 26539948 TI - Editor's Response. PMID- 26539949 TI - Varied Clinical Manifestations of Amebic Colitis. AB - Invasive amebiasis is common worldwide, but infrequently observed in the United States. It is associated with considerable morbidity in patients residing in or traveling to endemic areas. We review the clinical and endoscopic manifestations of amebic colitis to alert physicians to the varied clinical manifestations of this potentially life-threatening disease. Copyright (c)Most patients present with watery or bloody diarrhea. Less common presentations of amebic colitis include abdominal pain, overt gastrointestinal bleeding, exacerbation of inflammatory bowel disease, or the incidental association with colon cancer. Amebic liver abscesses are the most frequent complication. Rectosigmoid involvement may be found on colonoscopy; however, most case series have reported that the cecum is the most commonly involved site, followed by the ascending colon. Endoscopic evaluation should be used to assist in the diagnosis, with attention to the observation of colonic inflammation, ulceration, and amebic trophozoites on histopathological examination. PMID- 26539950 TI - Risk Factors for 30-Day Readmissions of Individuals with Decompensated Cirrhosis. AB - OBJECTIVES: Patients with cirrhosis have a high rate of 30-day hospital readmission that affects their quality of life and contributes to increased healthcare-related costs. The aim of our study was to identify frequency, predictors, and preventable causes of hospital readmissions among patients with decompensated cirrhosis. METHODS: We retrospectively reviewed electronic medical records of all patients with a confirmed diagnosis of decompensated cirrhosis admitted to Dayton VA Medical Center between 2009 and 2013. Demographics, clinical factors, laboratory values, and outcomes were recorded. Univariate analysis was performed using independent samples t tests and Wilcoxon rank sums tests for continuous variables and chi(2) or Fisher exact tests for categorical variables. A multiple logistic regression analysis was performed for variables found to be significant by univariate analysis to predict the risk factors for 30 day readmission. A detailed chart review was conducted for all patients readmitted within 30 days by a single gastroenterologist to identify the reason for readmission and to decide whether any of these readmissions were preventable. RESULTS: The 30-day readmission rate for decompensated cirrhotic patients was 27.03%. The risk factors for 30-day readmission were higher body mass index (BMI), lower body temperature, higher blood urea nitrogen, higher creatinine, more cirrhosis-related complications, and more readmissions per year per univariate analysis. Multivariable analysis revealed only BMI as a significant predictor of 30-day readmission (P = 0.023). A total of 36.7% of 30-day readmissions were possibly preventable. CONCLUSIONS: The independent variable that predicted 30-day readmission in patients with decompensated cirrhosis was higher BMI. Approximately one-third of 30-day readmissions were possibly preventable. These findings support the need to develop specific interventions for disease management to improve patient care and save on extraneous healthcare costs. PMID- 26539951 TI - Rest-Only Myocardial CT Perfusion in Acute Chest Pain. AB - OBJECTIVES: Cardiac computed tomography perfusion (CTP) using stress testing is an emerging application in the field of cardiac computed tomography. We evaluated patients with acute chest pain (CP) in the emergency department (ED) with evidence of obstructive coronary artery disease (CAD), defined as >70% stenosis on coronary computed tomography angiography (CCTA) and confirmed by invasive coronary angiography (ICA), to evaluate the applicability of resting CTP in the acute CP setting. METHODS: From January to December 2013, 183 low-intermediate risk symptomatic patients with negative cardiac biomarkers and no known CAD underwent a rapid CCTA protocol in the ED. Of these, 4 patients (1.4%) had obstructive CAD (>=70% stenosis) on CCTA confirmed by ICA. All 183 CCTA studies were evaluated retrospectively with CTP software by a transmural perfusion ratio (TPR) method with a superimposed 17-segment model. A TPR value <0.99 was considered abnormal based on previously published data. RESULTS: A total of four patients were included in this pilot analysis. The duration from resolution of CP to performance of CCTA ranged from 1.6 to 5.0 hours. Three patients underwent revascularization, two with percutaneous coronary intervention (PCI) and one with coronary artery bypass grafting. The fourth patient was managed with aggressive medical therapy. Two patients had multivessel obstructive CAD and two patients had single-vessel CAD. The first patient underwent CCTA 5 hours after resolution of CP symptoms. CCTA demonstrated noncalcified obstructive CAD in the mid-LAD and mid-right coronary artery. ICA showed good correlation by quantitative coronary assessment (QCA) in both vessels and the patient underwent PCI. CTP analysis demonstrated perfusion defects in the LAD and right coronary artery territories. The second patient underwent CCTA 1.6 hours after resolution of CP symptoms with findings of obstructive ostial left main CAD. ICA confirmed obstructive left main CAD by QCA and intravascular ultrasound. The patient underwent revascularization with coronary artery bypass grafting. CTP demonstrated perfusion defects in the anterior and lateral wall segments. The third patient was evaluated for CP in the ED with CCTA demonstrating single-vessel CAD 10 hours after resolution of symptoms with findings of a noncalcified obstructive stenosis in the mid-LAD. The patient subsequently underwent ICA demonstrating good correlation to the CCTA findings in the LAD by QCA. CTP analysis revealed perfusion defects in LAD territory. He was successful treated with PCI. The final patient underwent CCTA 5.4 hours following resolution of CP with the finding of an intermediate partially calcified stenosis in the distal LAD. ICA was performed, with fractional flow reserve demonstrating a hemodynamically insignificant distal LAD at 0.86. CTP detected a perfusion defect in the LAD territory. CONCLUSIONS: When positive, rest CTP may have value in the risk stratification of patients presenting to the ED with nontraumatic acute CP. PMID- 26539952 TI - Upper Gastrointestinal Involvement in Crohn Disease: Histopathologic and Endoscopic Findings. AB - OBJECTIVES: Studies describing the prevalence of upper gastrointestinal (GI) Crohn disease (CD) and its histopathologic changes have been inconsistent as a result of different definitions used for upper GI involvement, diverse populations, and varying indications for endoscopy. We reviewed the literature describing endoscopic findings and histologic lesions in gastric and duodenal mucosa of patients with established CD. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for gastroduodenal biopsy findings in patients with CD from 1970 to 2014. We included all retrospective and prospective studies in adults. We calculated the prevalence of the most common endoscopic and histopathological findings among patients with overall CD and upper GI CD. RESULTS: Of the 385 articles identified, 20 eligible studies were included. A total of 2511 patients had CD and 815 had upper GI CD. In the CD group, the most common histopathological finding was nonspecific gastric inflammation in 32% of patients, followed by gastric granuloma in 7.9%. Focal gastritis was prevalent in 30.9% of patients. In the upper GI CD group, gastric inflammation was present in 84% of patients, followed by duodenal inflammation in 28.2% and gastric granuloma in 23.2%. The most common gastric endoscopic finding in patients with CD was erythema in 5.9%, followed by erosions in 3.7%. Duodenal endoscopic findings included ulcers and erythema in 5.3% and 3.0% of patients, respectively. CONCLUSIONS: We found a prevalence of 34% for CD involving the upper GI tract across these 20 studies. Routine upper endoscopy with biopsies of the upper GI tract in the diagnostic workup of patients with CD can correctly classify the distribution and extent of the disease. PMID- 26539953 TI - Adapting an evidence-based model to retain adolescent study participants in longitudinal research. AB - Maintaining contact with and collecting outcome data from adolescent study participants can present a significant challenge for researchers conducting longitudinal studies. Establishing an organized and effective protocol for participant follow-up is crucial to reduce attrition and maintain high retention rates. This paper describes our methods in using and adapting the evidence-based Engagement, Verification, Maintenance, and Confirmation (EVMC) model to follow up with adolescents 6 and 12 months after implementation of a health program. It extends previous research by focusing on two key modifications to the model: (1) the central role of cell phones and texting to maintain contact with study participants throughout the EVMC process and, (2) use of responsive two-way communication between staff and participants and flexible administration modes and methods in the confirmation phase to ensure that busy teens not only respond to contacts, but also complete data collection. These strategies have resulted in high overall retention rates (87-91%) with adolescent study participants at each follow-up data collection point without the utilization of other, more involved tracking measures. The methods and findings presented may be valuable for other researchers with limited resources planning for or engaged in collecting follow up outcome data from adolescents enrolled in longitudinal studies. PMID- 26539954 TI - Spielvogel and CABG one time surgery followed by TEVAR to treat thoracic aneurism and pseudoaneurysms of the arch coexisting with a three coronary artery disease. PMID- 26539955 TI - A hypothesis: Cancer itself may cause cardiovascular damage directly or indirectly. PMID- 26539956 TI - A super high-pressure balloon solution for a non-dilatable in-stent restenosis. PMID- 26539958 TI - Atherosclerosis is critical in the pathogenesis of erectile dysfunction. PMID- 26539957 TI - Frame counting improves the assessment of post-reperfusion microvascular patency by TIMI myocardial perfusion grade: Evidence from cardiac magnetic resonance imaging. AB - BACKGROUND: Quantitative modification of TIMI myocardial perfusion grade (TMPG) by the method of frame counting may improve its sensitivity and the false negative rate for post-reperfusion microvascular dysfunction (MVD) in ST segment elevated myocardial infarction (STEMI) patients. METHODS: The durations of contrast-washout from infarction area of 139 patients were measured by counting the cine-frame numbers between the appearance and disappearance of myocardial blush. The achieved new index, TMP Frame Counting (TMP-FC) was referenced by cardiac magnetic resonance, by which MVD was defined as microvascular obstruction on gadolinium late-enhancement imaging. RESULTS: Median TMP-FC differed significantly between patients with and without MVD (126 frames, IQR 105-160 vs. 86 frames, IQR 75-100, p<0.001). By receiver-operating characteristic analysis, the cutoff of TMP-FC at >= 95.5 frames represented an independent predictor of MVD (OR=11.61, p<0.001). TMP-FC had similar specificity (75%) and positive predictive value (88%), but significantly improved sensitivity (85.3%) and negative predictive value (70.2%) for MVD compared with TMPG (88.6%, 86.5%, 33.7% and 38.2%, respectively) and other traditional angiographic assessments, leading to a better overall accuracy (area under the curve: 0.801 compared with 0.612 from TMPG, p<0.001) for the evaluation of microvascular patency. TMP-FC was positively correlated with MVD extent (r=0.5, p<0.001). Abnormal TMP-FC was associated with larger infarction size (28.67 +/- 13.72% vs. 16.51 +/- 10.68% of left ventricular mass, p<0.001) and lower LVEF (49.37 +/- 11.06% vs. 56.84 +/- 9.72%, p<0.001). CONCLUSION: Frame counting can improve the accuracy of TMPG for MVD. Moreover, TMP-FC is correlated with the degree of MVD and cardiac detriments, which is useful for risk stratification. PMID- 26539959 TI - Mid-regional pro-adrenomedullin and N-terminal pro B-type natriuretic peptide predict the recurrence of atrial fibrillation after cryoballoon pulmonary vein isolation. PMID- 26539960 TI - Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy. AB - BACKGROUND: The efficacy of oral anticoagulation therapy (OAT) has not been revealed in atrial fibrillation (AF) patients with newly diagnosed cancers. This study evaluated the thromboembolic and bleeding events in AF patients with malignancies according to OAT. METHODS AND RESULTS: In 2168 consecutive non valvular AF patients with newly diagnosed malignancies, we analyzed the composite endpoints including major adverse cardiac events (MACEs) and major bleeding. Based on a propensity score matching, two groups with 690 matched pairs were created. Patient baseline characteristics were comparable between the matched groups. During a follow-up period of 3.9 +/- 2.8 years, 72 (10%) and 65 (9%) patients had MACEs in the propensity score-matched OAT + and OAT - groups, respectively (p = 0.461). There was no significant difference in the major bleeding (10% vs. 8%, p = 0.300) and composite endpoints (18% vs. 16%, p = 0.181) between OAT + and OAT - patients. During the first year after the cancer diagnosis, 66 (48%) MACEs, 52 (41%) major bleedings, and 116 (49%) composite end points of all events occurred. The optimal international normalized ratio (2.0 to 3.0) level was achieved in only 85 (12%) patients. However, 1 year after cancer diagnosis, OAT + patients with the target therapeutic range of >= 60% demonstrated better cumulative survival free of composite end point than OAT - patients (p = 0.026). CONCLUSION: During the first year after the cancer diagnosis, OAT did not improve the composite end point because of poor INR control caused by cancer treatment. However, after 1 year after diagnosis of cancer, optimal anticoagulation significantly reduced the composite end point. PMID- 26539961 TI - A case of double fistulas of right coronary artery to LVOT and LAD. PMID- 26539962 TI - Macrophages dictate the progression and manifestation of hypertensive heart disease. AB - BACKGROUND: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. METHODS AND RESULTS: We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta 1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). CONCLUSIONS: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease. PMID- 26539963 TI - TET2 might be a therapeutic target for atherosclerosis. PMID- 26539964 TI - Triple head-to-head comparison of fibrotic biomarkers galectin-3, osteopontin and gremlin-1 for long-term prognosis in suspected and proven acute heart failure patients. AB - BACKGROUND: To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF). METHODS: Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years. RESULTS: 401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4-1.9; p = 0.03) and osteopontin (HR range 1.2-1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82-0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82-0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006). CONCLUSIONS: A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF. PMID- 26539965 TI - Leadless pacing: The old with the new. PMID- 26539966 TI - Sex hormones adjust "sex-specific" reactive and diurnal cortisol profiles. AB - Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles. PMID- 26539967 TI - Emotional attentional control predicts changes in diurnal cortisol secretion following exposure to a prolonged psychosocial stressor. AB - Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been associated with several psychological disorders. Hence, the identification of individual difference variables that predict variations in HPA-axis activity represents an important challenge for psychiatric research. We investigated whether self reported attentional control in emotionally demanding situations prospectively predicted changes in diurnal salivary cortisol secretion following exposure to a prolonged psychosocial stressor. Low ability to voluntarily control attention has previously been associated with anxiety and depressive symptomatology. Attentional control was assessed using the Emotional Attentional Control Scale. In students who were preparing for academic examination, salivary cortisol was assessed before (time 1) and after (time 2) examination. Results showed that lower levels of self-reported emotional attentional control at time 1 (N=90) predicted higher absolute diurnal cortisol secretion and a slower decline in cortisol throughout the day at time 2 (N=71). Difficulty controlling attention during emotional experiences may lead to chronic HPA-axis hyperactivity after prolonged exposure to stress. These results indicate that screening for individual differences may foster prediction of HPA-axis disturbances, paving the way for targeted disorder prevention. PMID- 26539968 TI - Correction: Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002243.]. PMID- 26539969 TI - Prospective and Pavlovian mechanisms in aversive behaviour. AB - Studying aversive behaviour is critical for understanding negative emotions and associated psychopathologies. However a comprehensive picture of the mechanisms underlying aversion is lacking, with associative learning theories focusing on Pavlovian reactions and decision-making theoretic approaches on prospective functions. We propose a computational model of aversion that combines goal directed and Pavlovian forms of control into a unifying framework in which their relative importance is regulated by factors such as threat distance and controllability. Using simulations, we test whether the model can reproduce available empirical findings and discuss its relevance to understanding factors underlying negative emotions such as fear and anxiety. Furthermore, the specific method used to construct the model permits a natural mapping from its components to brain structure and function. Our model provides a basis for a unifying account of aversion that can guide empirical and interventional study contexts. PMID- 26539970 TI - Fractionation of oil palm empty fruit bunch by bisulfite pretreatment for the production of bioethanol and high value products. AB - In this work, fractionation of empty fruit bunch (EFB) by bisulfite pretreatment was studied for the production of bioethanol and high value products to achieve biorefinery of EFB. EFB was fractionated to solid and liquor components by bisulfite process. The solid components were used for bioethanol production by quasi-simultaneous saccharification and fermentation. The liquor components were then converted to furfural by hydrolysis with sulfuric acid. Preliminary results showed that the concentration of furfural was highest at 18.8g/L with 0.75% sulfuric acid and reaction time of 25min. The conversion of xylose to furfural was 82.5%. Furthermore, we attempted to fractionate the liquor into hemicellulose sugars and lignin by different methods for producing potential chemicals, such as xylose, xylooligosaccharide, and lignosulfonate. Our research showed that the combination of bisulfite pretreatment and resin separation could effectively fractionate EFB components to produce bioethanol and other high value chemicals. PMID- 26539971 TI - Dual energy CT with photon counting and dual source systems: comparative evaluation. AB - Recently, new dual energy (DE) computed tomography (CT) systems-dual source CT (DSCT) and photon counting CT (PCCT) have been introduced. Although these systems have the same clinical targets, they have major differences as they use dual and single kVp acquisitions and different x-ray detection and energy resolution concepts. The purpose of this study was theoretical and experimental comparisons of DSCT and PCCT. The DSCT Siemens Somatom Flash was modeled for simulation study. The PCCT had the same configuration as DSCT except it used a photon counting detector. The soft tissue phantoms with 20, 30, and 38 cm diameters included iodine, CaCO3, adipose, and water samples. The dose (air kerma) was 14 mGy for all studies. The low and high energy CT data were simulated at 80 kVp and 140 kVp for DSCT, and in 20-58 keV and 59-120 keV energy ranges for PCCT, respectively. The experiments used Somatom Flash DSCT system and PCCT system based on photon counting CdZnTe detector with 2 * 256 pixel configuration and 1 * 1 mm(2) pixels size. In simulated general CT images, PCCT provided higher contrast-to-noise ratio (CNR) than DSCT with 0.4/0.8 mm Sn filters. The PCCT with K-edge filter provided higher CNR than the PCCT with a Cu filter, and DSCT with 0.4 mm Sn filter provided higher CNR than the DSCT with a 0.8 mm Sn filter. In simulated DE subtracted images, CNR of the DSCT was comparable to the PCCT with a Cu filter. However, DE PCCT with Ho a K-edge filter provided 30-40% higher CNR than the DE DSCT with 0.4/0.8 mm Sn filters. The experimental PCCT provided higher CNR in general imaging compared to the DSCT. In experimental DE subtracted images, the DSCT provided higher CNR than the PCCT with a Cu filter. However, experimental CNR with DE PCCT with K-edge filter was 15% higher than in DE DSCT, which is less than 30-40% increase predicted by the simulation study. It is concluded that ideal PCCT can provide substantial advantages over ideal DSCT in CT imaging including DE subtracted CT. However, the limitations of the PCCT detector does not allow it to reach its full potential and therefore further efforts are needed to improve PCCT detectors. PMID- 26539972 TI - Controlled Film Architectures to Detect a Biomarker for Pancreatic Cancer Using Impedance Spectroscopy. AB - The need for analytical devices for detecting cancer at early stages has motivated research into nanomaterials where synergy is sought to achieve high sensitivity and selectivity in low-cost biosensors. In this study, we developed a film architecture combining self-assembled monolayer (SAM) and layer-by-layer (LbL) films of polysaccharide chitosan and the protein concanavalin A, on which a layer of anti-CA19-9 antibody was adsorbed. Using impedance spectroscopy with this biosensor, we were capable of detecting low concentrations of the antigen CA19-9, an important biomarker for pancreatic cancer. The limit of detection of 0.69U/mL reached is sufficient for detecting pancreatic cancer at very early stages. The selectivity of the biosensor was inferred from a series of control experiments with samples of cell lines that were tested positive (HT29) and negative (SW620) for the biomarker CA19-9, in addition to the lack of changes in the capacitance value for other analytes and antigen that are not related to this type of cancer. The high sensitivity and selectivity are ascribed to the very specific antigen-antibody interaction, which was confirmed with PM-IRRAS and atomic force microscopy. Also significant is that used information visualization methods to show that different cell lines and commercial samples containing distinct concentrations of CA19-9 and other analytes can be easily distinguished from each other. These computational methods are generic and may be used in optimization procedures to tailor biosensors for specific purposes, as we demonstrated here by comparing the performance of two film architectures in which the concentration of chitosan was varied. PMID- 26539973 TI - Isolation and Structure of Kurahyne B and Total Synthesis of the Kurahynes. AB - Kurahyne B (2), a new analogue of kurahyne (1), was isolated from the marine cyanobacterium Okeania sp. Its gross structure was elucidated based on spectroscopic analyses, and the absolute configuration was established by total synthesis. Kurahyne B (2) inhibited the growth of both HeLa and HL60 cells, with IC50 values of 8.1 and 9.0 MUM, respectively. The growth-inhibitory activity of kurahyne B was the same as kurahyne (1). In parallel, the first total synthesis of kurahyne (1) was also achieved. PMID- 26539974 TI - Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions. AB - Aryl CH hydrogen bonds (HBs) are now commonly recognized as important factors in a number of fields, including molecular biology, stereoselective catalysis, and anion supramolecular chemistry. As the utility of CH HBs has grown, so to has the need to understand the structure-activity relationship for tuning both their strength and selectivity. Although there has been significant computational effort in this area, an experimental study of the substituent effects on CH HBs has not been previously undertaken. Herein we disclose a systematic study of a single CH HB by using traditional urea donors as directing groups in a supramolecular binding cavity. Experimentally determined association constants are examined by a combination of computational (electrostatic potential) and empirical (sigmam and sigmap) values for substituent effects. The dominance of electrostatic parameters, as observed in a computational DFT study, is consistent with current CH HB theory; however, a novel anion dependence of the substituent effects is revealed in solution. PMID- 26539975 TI - Telomere length, cardiovascular risk and arteriosclerosis in human kidneys: an observational cohort study. AB - BACKGROUND: Replicative senescence, associated with telomere shortening, plays an important role in aging and cardiovascular disease. The relation between telomere length, cardiovascular risk, and renal disease is unknown. METHODS: Our study consisted of a cohort of 257 kidney donors for transplantation, divided into a test and a validation cohort. We used quantitative RT-PCR to measure relative telomere length (log T/S ratio) in peripheral blood leucocytes, and in kidney biopsies performed prior to implantation. The association between leucocyte and intrarenal telomere length, cardiovascular risk factors, and renal histology, was studied using multiple regression models, adjusted for calendar age, gender and other donor demographics. RESULTS: Subjects with intrarenal arteriosclerosis had significantly shorter leucocyte telomere length compared with patients without arteriosclerosis (log T/S ratio -0.3+/-0.4 vs. 0.1+/-0.2 with vs. without arteriosclerosis; p=0.0008). Intrarenal arteriosclerosis was associated with shorter telomere length, independent of gender, calendar age, history of hypertension and history of cardiovascular events. For each increase of one standard deviation of the log T/S ratio, the odds for intrarenal arteriosclerosis decreased with 64% (Odds ratio 0.36; 95% CI 0.17-0.77; p=0.02). In accordance with leucocyte telomere length, shorter intrarenal telomere length associated significantly with the presence of renal arteriosclerosis (log T/S ratio -0.04+/ 0.06 vs. 0.08+/-0.01 with vs. without arteriosclerosis, p=0.007), and not with other histological lesions. INTERPRETATION: We demonstrate that arteriosclerosis in smaller intrarenal arteries is associated with shorter telomere length. Our study suggests a central role of replicative senescence in the progression of renovascular disease, independent of calendar age. PMID- 26539976 TI - Protopanaxadiol aglycone ginsenoside-polyethylene glycol conjugates: synthesis, physicochemical characterizations, and in vitro studies. AB - Ginsenosides are triterpenoid saponins, which is an active compound responsible for most of the pharmacological effects of ginseng (Panax ginseng Meyer). It is known to have numerous structural and pharmacological properties. However, aqueous solubility and delivery of ginsenosides in targeted region by avoiding undesirable toxicity to normal cell is also of prime importance. The aim of this study was to obtain amphiphilic ginsenoside derivatives in which hydrophilic polymers were conjugated to ginsenosides to enhance the water solubility and targeted delivery. To this end, the hydrophobic protopanaxadiol ginsenoside aglycone (aPPD) was covalently conjugated to the backbone of hydrophilic polyethylene glycol (PEG) through a pH sensitive ester linkage, which was confirmed by 1H NMR and FTIR. The resultant PPD is covalently conjugated to hydrophilic PEG through esterification (PEG-PPD) forming self-assembled spherical nanoparticles, whose average particle diameter was 189 nm as observed by FE-TEM and particle size analyzer respectively. In vitro release experiments revealed that the release rate of PPD was rapidly increased from the self-assembled nanoparticles under acidic conditions (pH 5.0) than in a physiological buffer (pH 7.4) condition. Furthermore, in vitro cytotoxicity assays revealed that PEG-PPD conjugates exhibited lower cytotoxicity in HT-29 cancer cells compared with PPD alone. Since the slow release of PPD from conjugates is triggered only by acidic environmental conditions, such as those found in extracellular solid tumor tissues, intracellular endosomes, and intracellular lysosomes, the conjugation of PPD may aid its selective delivery to these targets. Overall, results suggest that pH-dependent release of PPD, which expected in reduced cytotoxicity to non targeted regions, may enhance the overall efficacy of PPD. PMID- 26539978 TI - The Survival and Resistance of Halobacterium salinarum NRC-1, Halococcus hamelinensis, and Halococcus morrhuae to Simulated Outer Space Solar Radiation. AB - Solar radiation is among the most prominent stress factors organisms face during space travel and possibly on other planets. Our analysis of three different halophilic archaea, namely Halobacterium salinarum NRC-1, Halococcus morrhuae, and Halococcus hamelinensis, which were exposed to simulated solar radiation in either dried or liquid state, showed tremendous differences in tolerance and survivability. We found that Hcc. hamelinensis is not able to withstand high fluences of simulated solar radiation compared to the other tested organisms. These results can be correlated to significant differences in genomic integrity following exposure, as visualized by random amplified polymorphic DNA (RAPD)-PCR. In contrast to the other two tested strains, Hcc. hamelinensis accumulates compatible solutes such as trehalose for osmoprotection. The addition of 100 mM trehalose to the growth medium of Hcc. hamelinensis improved its survivability following exposure. Exposure of cells in liquid at different temperatures suggests that Hbt. salinarum NRC-1 is actively repairing cellular and DNA damage during exposure, whereas Hcc. morrhuae exhibits no difference in survival. For Hcc. morrhuae, the high resistance against simulated solar radiation may be explained with the formation of cell clusters. Our experiments showed that these clusters shield cells on the inside against simulated solar radiation, which results in better survival rates at higher fluences when compared to Hbt. salinarum NRC-1 and Hcc. hamelinensis. Overall, this study shows that some halophilic archaea are highly resistant to simulated solar radiation and that they are of high astrobiological significance. KEY WORDS: Halophiles-Solar radiation-Stress resistance-Survival. PMID- 26539979 TI - Clinical Criteria for Physician Aid in Dying. AB - More than 20 years ago, even before voters in Oregon had enacted the first aid in dying (AID) statute in the United States, Timothy Quill and colleagues proposed clinical criteria AID. Their proposal was carefully considered and temperate, but there were little data on the practice of AID at the time. (With AID, a physician writes a prescription for life-ending medication for a terminally ill, mentally capacitated adult.) With the passage of time, a substantial body of data on AID has developed from the states of Oregon and Washington. For more than 17 years, physicians in Oregon have been authorized to provide a prescription for AID. Accordingly, we have updated the clinical criteria of Quill, et al., based on the many years of experience with AID. With more jurisdictions authorizing AID, it is critical that physicians can turn to reliable clinical criteria. As with any medical practice, AID must be provided in a safe and effective manner. Physicians need to know (1) how to respond to a patient's inquiry about AID, (2) how to assess patient decision making capacity, and (3) how to address a range of other issues that may arise. To ensure that physicians have the guidance they need, Compassion & Choices convened the Physician Aid-in-Dying Clinical Criteria Committee, in July 2012, to create clinical criteria for physicians who are willing to provide AID to patients who request it. The committee includes experts in medicine, law, bioethics, hospice, nursing, social work, and pharmacy. Using an iterative consensus process, the Committee drafted the criteria over a one year period. PMID- 26539980 TI - Reconstitution of biosynthetic machinery of fungal polyketides: unexpected oxidations of biosynthetic intermediates by expression host. AB - Reconstitution of whole biosynthetic genes in Aspergillus oryzae has successfully applied for total biosynthesis of various fungal natural products. Heterologous production of fungal metabolites sometimes suffers unexpected side reactions by host enzymes. In the studies on fungal polyketides solanapyrone and cytochalasin, unexpected oxidations of terminal olefin of biosynthetic intermediates were found to give one and four by-products by host enzymes of the transformants harboring biosynthetic genes. In this paper, we reported structure determination of by products and described a simple solution to avoid the undesired reaction by introducing the downstream gene in the heterologous production of solanapyrone C. PMID- 26539981 TI - Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial. AB - OBJECTIVE: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes. METHODS: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants. RESULTS: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1. CONCLUSIONS: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT00774462. PMID- 26539982 TI - Caffeine Ingestion Increases Estimated Glycolytic Metabolism during Taekwondo Combat Simulation but Does Not Improve Performance or Parasympathetic Reactivation. AB - OBJECTIVES: The aim of this study was to evaluate the effect of caffeine ingestion on performance and estimated energy system contribution during simulated taekwondo combat and on post-exercise parasympathetic reactivation. METHODS: Ten taekwondo athletes completed two experimental sessions separated by at least 48 hours. Athletes consumed a capsule containing either caffeine (5 mg?kg-1) or placebo (cellulose) one hour before the combat simulation (3 rounds of 2 min separated by 1 min passive recovery), in a double-blind, randomized, repeated-measures crossover design. All simulated combat was filmed to quantify the time spent fighting in each round. Lactate concentration and rating of perceived exertion were measured before and after each round, while heart rate (HR) and the estimated contribution of the oxidative (WAER), ATP-PCr (WPCR), and glycolytic (W[La-]) systems were calculated during the combat simulation. Furthermore, parasympathetic reactivation after the combat simulation was evaluated through 1) taking absolute difference between the final HR observed at the end of third round and the HR recorded 60-s after (HRR60s), 2) taking the time constant of HR decay obtained by fitting the 6-min post-exercise HRR into a first-order exponential decay curve (HRRtau), or by 3) analyzing the first 30-s via logarithmic regression analysis (T30). RESULTS: Caffeine ingestion increased estimated glycolytic energy contribution in relation to placebo (12.5 +/- 1.7 kJ and 8.9 +/- 1.2 kJ, P = 0.04). However, caffeine did not improve performance as measured by attack number (CAF: 26. 7 +/- 1.9; PLA: 27.3 +/- 2.1, P = 0.48) or attack time (CAF: 33.8 +/- 1.9 s; PLA: 36.6 +/- 4.5 s, P = 0.58). Similarly, RPE (CAF: 11.7 +/- 0.4 a.u.; PLA: 11.5 +/- 0.3 a.u., P = 0.62), HR (CAF: 170 +/- 3.5 bpm; PLA: 174.2 bpm, P = 0.12), oxidative (CAF: 109.3 +/- 4.5 kJ; PLA: 107.9 kJ, P = 0.61) and ATP-PCr energy contributions (CAF: 45.3 +/- 3.4 kJ; PLA: 46.8 +/- 3.6 kJ, P = 0.72) during the combat simulation were unaffected. Furthermore, T30 (CAF: 869.1 +/- 323.2 s; PLA: 735.5 +/- 232.2 s, P = 0.58), HRR60s (CAF: 34 +/- 8 bpm; PLA: 38 +/- 9 bpm, P = 0.44), HRRtau (CAF: 182.9 +/- 40.5 s, PLA: 160.3 +/- 62.2 s, P = 0.23) and HRRamp (CAF: 70.2 +/- 17.4 bpm; PLA: 79.2 +/- 17.4 bpm, P = 0.16) were not affected by caffeine ingestion. CONCLUSIONS: Caffeine ingestion increased the estimated glycolytic contribution during taekwondo combat simulation, but this did not result in any changes in performance, perceived exertion or parasympathetic reactivation. PMID- 26539983 TI - Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells. AB - HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging as a highly specific viral target for therapeutic elimination of the persistent HIV-infected reservoirs via antibody-mediated cell killing. Dual-Affinity Re-Targeting (DART) molecules exhibit a distinct mechanism of action via binding the cell surface target antigen and simultaneously engaging CD3 on cytotoxic T lymphocytes (CTLs). We designed and evaluated Env-specific DARTs (HIVxCD3 DARTs) derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. HIVxCD3 DARTs derived from PGT121, PGT145, A32, and 7B2, but not VRC01 or 10E8 antibodies, mediated potent CTL-dependent killing of quiescent primary CD4 T cells infected with diverse HIV isolates. Similar killing activity was also observed with DARTs structurally modified for in vivo half-life extension. In an ex vivo model using cells isolated from HIV-infected participants on cART, combinations of the most potent HIVxCD3 DARTs reduced HIV expression both in quiescent and activated peripheral blood mononuclear cell cultures isolated from HIV-infected participants on suppressive cART. Importantly, HIVxCD3 DARTs did not induce cell-to-cell virus spread in resting or activated CD4 T cell cultures. Collectively, these results provide support for further development of HIVxCD3 DARTs as a promising therapeutic strategy for targeting HIV reservoirs. PMID- 26539984 TI - Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy. AB - OBJECTIVE: In vivo Corneal Confocal Microscopy (IVCCM) is a validated, non invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis. METHODS: In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4+/-17.3y, HbA1c 5.5+/ 0.4%) and 26 participants with type 1 diabetes (42.8+/-16.9y, 8.0+/-1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols. RESULTS: Mean CNFLManual was 16.7+/-4.0, 13.9+/-4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2+/-3.3, 8.6+/-3.0 mm/mm2 and CNFLFully-Automated was 12.5+/-2.8, 10.9 +/- 2.9 mm/mm2. Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFLFully-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi Automated and CNFLFully-Automated underestimated CNFLManual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively. CONCLUSIONS: Despite an apparent measurement (underestimation) bias in comparison to the manual strategy of image analysis, fully-automated analysis preserves CNFL reproducibility. Future work must determine the diagnostic thresholds specific to the fully automated measure of CNFL. PMID- 26539985 TI - Modeling Healthcare Processes Using Commitments: An Empirical Evaluation. AB - The two primary objectives of this paper are: (a) to demonstrate how Comma, a business modeling methodology based on commitments, can be applied in healthcare process modeling, and (b) to evaluate the effectiveness of such an approach in producing healthcare process models. We apply the Comma approach on a breast cancer diagnosis process adapted from an HHS committee report, and presents the results of an empirical study that compares Comma with a traditional approach based on the HL7 Messaging Standard (Traditional-HL7). Our empirical study involved 47 subjects, and two phases. In the first phase, we partitioned the subjects into two approximately equal groups. We gave each group the same requirements based on a process scenario for breast cancer diagnosis. Members of one group first applied Traditional-HL7 and then Comma whereas members of the second group first applied Comma and then Traditional-HL7-each on the above mentioned requirements. Thus, each subject produced two models, each model being a set of UML Sequence Diagrams. In the second phase, we repartitioned the subjects into two groups with approximately equal distributions from both original groups. We developed exemplar Traditional-HL7 and Comma models; we gave one repartitioned group our Traditional-HL7 model and the other repartitioned group our Comma model. We provided the same changed set of requirements to all subjects and asked them to modify the provided exemplar model to satisfy the new requirements. We assessed solutions produced by subjects in both phases with respect to measures of flexibility, time, difficulty, objective quality, and subjective quality. Our study found that Comma is superior to Traditional-HL7 in flexibility and objective quality as validated via Student's t-test to the 10% level of significance. Comma is a promising new approach for modeling healthcare processes. Further gains could be made through improved tooling and enhanced training of modeling personnel. PMID- 26539986 TI - Agricultural Genomics: Commercial Applications Bring Increased Basic Research Power. PMID- 26539988 TI - A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010. AB - BACKGROUND: Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children. METHODS: Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs. RESULTS: The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (>=6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P <0.0001). CONCLUSIONS: The annual incidence of CPP has substantially increased among Korean girls over the past 7 years. Continued monitoring of CPP trends among Korean children will be informative. PMID- 26539987 TI - The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration. AB - BACKGROUND: Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). METHODS: Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. RESULTS: The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2% 10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P <= .01). CONCLUSION: Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally. PMID- 26539989 TI - Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease. AB - BACKGROUND: The intestine is one of the first affected organs in Parkinson's disease (PD). PD subjects show abnormal staining for Escherichia coli and alpha synuclein in the colon. METHODS: We recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing. RESULTS: In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD. CONCLUSIONS: The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD. PMID- 26539990 TI - Which Dimensions of Patient-Centeredness Matter? - Results of a Web-Based Expert Delphi Survey. AB - BACKGROUND: Present models and definitions of patient-centeredness revealed a lack of conceptual clarity. Based on a prior systematic literature review, we developed an integrative model with 15 dimensions of patient-centeredness. The aims of this study were to 1) validate, and 2) prioritize these dimensions. METHOD: A two-round web-based Delphi study was conducted. 297 international experts were invited to participate. In round one they were asked to 1) give an individual rating on a nine-point-scale on relevance and clarity of the dimensions, 2) add missing dimensions, and 3) prioritize the dimensions. In round two, experts received feedback about the results of round one and were asked to reflect and re-rate their own results. The cut-off for the validation of a dimension was a median < 7 on one of the criteria. RESULTS: 105 experts participated in round one and 71 in round two. In round one, one new dimension was suggested and included for discussion in round two. In round two, this dimension did not reach sufficient ratings to be included in the model. Eleven dimensions reached a median >= 7 on both criteria (relevance and clarity). Four dimensions had a median < 7 on one or both criteria. The five dimensions rated as most important were: patient as a unique person, patient involvement in care, patient information, clinician-patient communication and patient empowerment. DISCUSSION: 11 out of the 15 dimensions have been validated through experts' ratings. Further research on the four dimensions that received insufficient ratings is recommended. The priority order of the dimensions can help researchers and clinicians to focus on the most important dimensions of patient-centeredness. Overall, the model provides a useful framework that can be used in the development of measures, interventions, and medical education curricula, as well as the adoption of a new perspective in health policy. PMID- 26539991 TI - Cardiac-Specific Activation of IKK2 Leads to Defects in Heart Development and Embryonic Lethality. AB - The transcription factor NF-kappaB has been associated with a range of pathological conditions of the heart, mainly based on its function as a master regulator of inflammation and pro-survival factor. Here, we addressed the question what effects activation of NF-kappaB can have during murine heart development. We expressed a constitutively active (CA) mutant of IKK2, the kinase activating canonical NF-kappaB signaling, specifically in cardiomyocytes under the control of the alpha-myosin heavy chain promoter. Expression of IKK2-CA resulted in embryonic lethality around E13. Embryos showed defects in compact zone formation and the contractile apparatus, and overall were characterized by widespread inflammation with infiltration of myeloid cells. Gene expression analysis suggested an interferon type I signature, with increased expression of interferon regulatory factors. While apoptosis of cardiomyocytes was only increased at later stages, their proliferation was decreased early on, providing an explanation for the disturbed compact zone formation. Mechanistically, this could be explained by activation of the JAK/STAT axis and increased expression of the cell cycle inhibitor p21. A rescue experiment with an IkappaBalpha superrepressor demonstrated that the phenotype was dependent on NF-kappaB. We conclude that activation of NF-kappaB is detrimental during normal heart development due to excessive activation of pro-inflammatory pathways. PMID- 26539992 TI - Molecular Phylogeny and Ecology of Textularia agglutinans d'Orbigny from the Mediterranean Coast of Israel: A Case of a Successful New Incumbent. AB - Textularia agglutinans d'Orbigny is a non-symbiont bearing and comparatively large benthic foraminiferal species with a widespread distribution across all oceans. In recent years, its populations have considerably expanded along the Israeli Mediterranean coast of the eastern Levantine basin. Despite its exceptionally widespread occurrence, no molecular data have yet been obtained. This study provides the first ribosomal DNA sequences of T. agglutinans complemented with morphological and ecological characterization, which are based on material collected during environmental monitoring of the hard bottom habitats along the Israeli Mediterranean coast, and from the Gulf of Elat (northern Red Sea). Our phylogenetic analyses reveal that all specimens from both provinces belong to the same genetic population, regardless their morphological variability. These results indicate that modern population of T. agglutinans found on the Mediterranean coast of Israel is probably Lessepsian. Our study also reveals that T. agglutinans has an epiphytic life mode, which probably enabled its successful colonization of the hard bottom habitats, at the Mediterranean coast of Israel, which consist of a diverse community of macroalgae. Our study further indicates that the species does not tolerate high SST (> 35 degrees C), which will probably prevent its future expansion in the easternmost Mediterranean in light of the expected rise in temperatures. PMID- 26539993 TI - Serum beta-Defensin-2 Levels and Their Relationship with the Clinical Course and Prognosis in Patients with Crimean-Congo Hemorrhagic Fever. AB - OBJECTIVE: The aim of this study was to investigate the role of the clinical course and prognosis of serum levels of beta-defensin-2 (BD-2) in patients with Crimean-Congo hemorrhagic fever (CCHF). SUBJECTS AND METHODS: Patients who were hospitalized in the Department of Infectious Diseases and Clinical Microbiology of the Faculty of Medicine, Ataturk University, were considered for inclusion in this study. The patients had positive real-time reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay results of the CCHF virus. There were 60 patients with CCHF in the study group and 25 healthy participants in the control group. Serum BD-2 levels were measured using ELISA. Data were analyzed using the Student t test or Mann-Whitney U test. RESULTS: Of the 60 patients, 6 (10%) died and 54 (90%) were discharged following their recovery. The mean BD-2 level of the patient group was significantly higher (4,180.30 +/- 3,944.19 pg/ml) than that of the control group (964.45 +/- 266.07 pg/ml; p = 0.001). Serum BD-2 levels of the patients with fatal (1,529.81 +/- 1,028.14) and nonfatal disease (4,474.80 +/- 4,041.58) differed, but this difference showed only borderline significance (p = 0.055). The mean BD-2 level of the severe group was 5,507.45 +/- 4,327.06 pg/ml, while it was 3,611.52 +/- 3,676.73 pg/ml in the mild/moderate group, and both were significantly higher than that of the control group (p = 0.001). CONCLUSION: In this study, the expression of serum BD-2 was raised in patients with CCHF, and this increase may beneficially affect survival. Studies with larger sample sizes are needed to confirm the association of serum BD-2 with CCHF prognosis. PMID- 26539994 TI - Emotional eating and Pavlovian learning: evidence for conditioned appetitive responding to negative emotional states. AB - Appetitive learning has been demonstrated several times using neutral cues or contexts as a predictor of food intake and it has been shown that humans easily learn cued desires for foods. It has, however, never been studied whether internal cues are also capable of appetitive conditioning. In this study, we tested whether humans can learn cued eating desires to negative moods as conditioned stimuli (CS), thereby offering a potential explanation of emotional eating (EE). Female participants were randomly presented with 10 different stimuli eliciting either negative or neutral emotional states, with one of these states paired with eating chocolate. Expectancy to eat, desire to eat, salivation, and unpleasantness of experiencing negative emotions were assessed. After conditioning, participants were brought into a negative emotional state and were asked to choose between money and chocolate. Data showed differential conditioned responding on the expectancy and desire measures, but not on salivation. Specific conditioned effects were obtained for participants with a higher BMI (body mass index) on the choice task, and for participants high on EE on the unpleasantness ratings. These findings provide the first experimental evidence for the idea that negative emotions can act as conditioned stimuli, and might suggest that classical conditioning is involved in EE. PMID- 26539995 TI - Fructo-oligosaccharide improved brain beta-amyloid, beta-secretase, cognitive function, and plasma antioxidant levels in D-galactose-treated Balb/cJ mice. AB - OBJECTIVES: Long-term d-galactose injection induces accelerated aging in experimental rodent models. The aim of this study was to determine the effects of dietary fructo-oligosaccharide (FO) on the brain beta-amyloid (Abeta), amyloid associated enzymes, cognitive function, and plasma antioxidant levels in d galactose-treated Balb/c mice. METHODS: The subcutaneous (s.c.) injection and the dietary treatment were conducted simultaneously for 49 days. Mice (12 weeks of age) were divided into five groups (n = 14/group): control (s.c. saline, control diet) serving as a young control, DG (s.c. 1.2 g d-galactose/kg body weight, control diet), DG + LFO (2.5% w/w FO, low-dose FO diet), DG + HFO (5% w/w FO, high-dose FO diet), and DG + E (alpha-tocopherol 0.2% w/w, vitamin E diet) as an antioxidant reference group. Another group of older mice (64 weeks of age) without any injection served as a natural aging (NA) group. RESULTS: The DG and NA groups had greater Abeta levels in the cortex, hippocampus, and the whole brain. High-dose FO, similar to alpha-tocopherol, attenuated the d-galactose induced Abeta density in the cortex and hippocampus. In addition, FO attenuated the d-galactose-induced protein expression of Abeta and beta-site amyloid precursor cleaving enzyme of the whole brain in a dose-response manner. Either dose of FO supplementation, similar to alpha-tocopherol, attenuated the d galactose-induced cognitive dysfunction. In addition, FO improved the plasma ascorbic acid level in a dose-response manner. CONCLUSION: Dietary FO (2.5-5% w/w diet) could attenuate the development of Alzheimer's disease, which was likely to be associated with its systematic antioxidant effects. PMID- 26539996 TI - Update On CROES At The WCE Meeting In London. PMID- 26539997 TI - Loneliness and Health in Older Adults: A Mini-Review and Synthesis. AB - Increasing evidence suggests that perceived social isolation or loneliness is a major risk factor for physical and mental illness in later life. This review assesses the status of research on loneliness and health in older adults. Key concepts and definitions of loneliness are identified, and the prevalence, correlates, and health effects of loneliness in older individuals are reviewed. Theoretical mechanisms that underlie the association between loneliness and health are also described, and illustrative studies examining these mechanisms are summarized. Intervention approaches to reduce loneliness in old age are highlighted, and priority recommendations for future research are presented. PMID- 26539998 TI - Intraoperative Evaluation of Ureteral Access Sheath-Related Injuries Using Post Ureteroscopic Lesion Scale. AB - OBJECTIVE: In the present study, intraoperative ureteral injuries inflicted during retrograde intrarenal surgery (RIRS) with ureteral access sheath (UAS) use were evaluated using the Post- Ureteroscopic Lesion Scale (PULS). MATERIALS AND METHODS: Patients in whom a UAS was used during RIRS and for whom ureter images were video recorded during the procedure were included in the study. PULS grading was performed after UAS removal, and video sequences of all patients were viewed by a junior resident, a senior resident, and four experienced urologists and assessed according to the PULS. Ureteral lesions in distal, middle, proximal, and multiple locations were evaluated and compared according to the PULS scale. The inter-rater reliability of PULS grading among various urologists was also evaluated. RESULTS: The evaluation comprised 101 patients. In 77 patients, 9.5/11.5 French UAS devices were used, and in 24 patients, 12/14 French UAS devices were used. The stone-free rate, clinical insignificant residual fragments, and final stone-free rate were 41.6%, 53.5%, and 98%, respectively. In 58.4% of the patients, no lesions were present according to PULS grading. No lesions of Grade 3 and above were found; however, there were lesions of Grade 1 and 2 in 38.6% and 2.9% of the patients, respectively. Injuries were found in the proximal ureter only and distal ureter only in 45.23% and 40.47% of the patients, respectively. Multiple injuries occurred in 5.94% of the patients (in 3.96% in the proximal and distal ureter, in 0.99% in the mid- and distal ureter, and in 0,99% in the proximal, mid-, and distal ureter). In the grading performed according to the PULS classification, there was a high accuracy among the residents and specialists. CONCLUSIONS: The assessment of UAS-induced injuries using standardized intraoperative methods will help to evaluate the procedure more objectively and will guide the postoperative follow-up of patients. PMID- 26539999 TI - Impact of magnetic resonance imaging-guided prostate biopsy in the supine position on the detection of significant prostate cancer in an inhomogeneous patient cohort. AB - OBJECTIVE: The aim of this study was to determine the tumour detection rate of magnetic resonance-guided biopsy (MRGB) in the supine position for significant prostate cancer in an inhomogeneous patient cohort. MATERIALS AND METHODS: Thirty two consecutive patients with a total prostate-specific antigen > 4 ng/ml and/or a tumour-suspicious palpable lesion upon digital rectal examination and a cancer suspicious region in multiparametric magnetic resonance imaging (MRI) underwent MRGB in a standard 1.5 T magnet. Diagnostic MRI was performed in 20 patients at the authors' institute and 12 men at another location. Eight patients were investigated at 3 T and 24 at 1.5 T. Twenty men had prior negative biopsies and 12 were biopsy naive. All biopsies were performed in the supine position using a table-mounted device and an 18 G biopsy gun. RESULTS: The overall tumour detection rate was 53% (17/32). Two cores (median; range 1-4) were extracted. Clinically significant cancers were found in 94% (16/17). None of the patients showed any postbiopsy complications. The prostate volumes of patients with cancer were significantly lower (39.3 ml) than those of men without cancer (49.7 ml). No significant differences were found between the numbers of tumour-positive and tumour-negative collected cores. In a median follow-up of 14 months, no cancer was detected in the negative biopsy group. CONCLUSION: MRGB in the supine position can be a valuable tool to detect significant prostate cancer, even in a patient cohort with different prebiopsy pathways. The biopsy method could be a reasonable alternative to MRGB in the prone position. PMID- 26540004 TI - Peculiarity of Porcine Amniotic Membrane and Its Derived Cells: A Contribution to the Study of Cell Therapy from a Large Animal Model. AB - The aim of this work was to provide, for the first time, a protocol for isolation and characterization of stem cells from porcine amniotic membrane in view of their potential uses in regenerative medicine. From three samples of allanto amnion recovered at delivery, the amniotic membrane was stripped from overlying allantois and digested with trypsin and collagenase to isolate epithelial (amniotic epithelial cells [AECs]) and mesenchymal cells, respectively. Proliferation, differentiation, and characterization studies by molecular biology and flow cytometry were performed. Histological examination revealed very few mesenchymal cells in the stromal layer, and a cellular yield of AECs of 10 * 10(6)/gram of digested tissue was achieved. AECs readily attached to plastic culture dishes displaying typical cuboidal morphology and, although their proliferative capacity decreased to the fifth passage, AECs showed a mean doubling time of 24.77 +/- 6 h and a mean frequency of one fibroblast colony forming unit (CFU-F) for every 116.75 plated cells. AECs expressed mesenchymal stem cell (MSC) mRNA markers (CD29, CD166, CD90, CD73, CD117) and pluripotent markers (Nanog and Oct 4), whereas they were negative for CD34 and MHCII. Mesodermic, ectodermic, and endodermic differentiation was confirmed by staining and expression of specific markers. We conclude that porcine amniotic membrane can provide an attractive source of stem cells that may be a useful tool for biomedical research. PMID- 26540006 TI - Interaction of partially denatured insulin with a DSPC floating lipid bilayer. AB - The carefully controlled permeability of cellular membranes to biological molecules is key to life. In degenerative diseases associated with protein misfolding and aggregation, protein molecules or their aggregates are believed to permeate these barriers and threaten membrane integrity. We used neutron reflectivity to study the interaction of insulin, a model amyloidogenic protein, with a DSPC floating lipid bilayer. Structural changes consistent with protein partitioning to the membrane interior and adsorption to a gel phase model lipid bilayer were observed under conditions where the native fold of the protein is significantly destabilised. We propose that the perturbation of the membrane by misfolded proteins involves long term occupation of the membrane by these proteins, rather than transient perforation events. PMID- 26540005 TI - The complete chloroplast genome of Ostrya rehderiana. AB - The complete chloroplast sequence of Ostrya rehderiana is 159 347 bp in length, containing 85 protein-coding genes, 8 ribosomal RNA genes, and 31 transfer RNA genes. The circular genome exhibits a typical chloroplast genome structure comprising a large single copy region of 88 552 bp, a small single copy region of 18 941 bp and a pair of inverted repeats of 25 927 bp. The overall GC content of the chloroplast genome is 36.5%. Phylogenetic analysis of O. rehderiana sequence together with 12 complete chloroplast genomes revealed a basal placement of O. rehderiana within the Fagales species. PMID- 26540008 TI - Presentation, diagnosis and management of neck abscesses in children. AB - The aim of the study was to analyze the presenting signs and symptoms, diagnostic procedures, clinical course, pathogenic organisms and management of neck abscesses in children. MATERIALS AND METHODS: This retrospective medical records review comprised of 51 pediatric cases referred because of neck abscess from 2001 to 2014. Medical records of the patients were reviewed for demographic data, clinical presentation, treatment before referral, localization of the abscess, imaging evaluation, medical and surgical treatment, bacteriological data and complications. RESULTS: Average age of the patients was 4.9 years. 18 (35%) of the children were below one year of age. The submandibular was the most common area involved (41,2%). Contrast-enhanced computed tomography (CECT) was performed in 45% of patients mainly with deep neck abscesses. All CECT scans showed the fluid collections. In all but one of the patients treated surgically and diagnosed with ultrasound and/or CECT surgical intervention revealed presence of pus. The most common pathogen was Staphylococcus aureus- SA (78% of all isolates) of which 24% were methicillin resistant Staphylococcus aureus - MRSA. Clindamycin resistance was detected in 28% of all SA isolates and in 67% (4/6) of all MRSA isolates. All MRSA isolates were sensitive to vancomycin. CONCLUSIONS: CECT is reliable imaging technique for diagnosing deep neck abscesses in children. Infants with neck abscesses are at higher risk of having MRSA as offending pathogen which should be taken into consideration when considering empiric treatment. Vancomycin is recommended as empiric antibiotic therapy in newborns with neck abscess. PMID- 26540009 TI - Evaluation of central auditory processing in children with Specific Language Impairment. AB - Specific Language Impairment (SLI) affects about 7-15 % of children of school age and according to the currently accepted diagnostic criteria, it is presumed that these children do not suffer from hearing impairment. The goal of this work was to assess anomalies of central auditory processes in a group of children diagnosed with specific language impairment. Material consisted of 200 children aged 7-10 years (100 children in the study group and 100 hundred in the control group). Selected psychoacoustic tests (Frequency Pattern Test - FPT, Duration Pattern Test - DPT, Dichotic Digit Test - DDT, Time Compressed Sentence Test - CST, Gap Detection Test - GDT) were performed in all children. Results were subject to statistical analysis. It was observed that mean results obtained in individual age groups in the study group are significantly lower than in the control group. Based on the conducted studies we may conclude that children with SLI suffer from disorders of some higher auditory functions, which substantiates the diagnosis of hearing disorders according to the AHSA (American Hearing and Speech Association) guidelines. Use of sound-based, not verbal tests, eliminates the probability that observed problems with perception involve only perception of speech, therefore do not signify central hearing disorders, but problems with understanding of speech. Lack of literature data on the significance of FPT, DPT, DDT, CST and GDT tests in children with specific language impairment precludes comparison of acquired results and makes them unique. PMID- 26540010 TI - Discovery of a secular trend in Cayo Santiago macaque reproduction. AB - Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3 month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of <365 days in average and the proportion of these females increased up to 48% due to changes in colony management overtime, although reproductive synchrony increased with increasing population density. A secular trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. PMID- 26540011 TI - Capillary Printing of Highly Aligned Silver Nanowire Transparent Electrodes for High-Performance Optoelectronic Devices. AB - Percolation networks of silver nanowires (AgNWs) are commonly used as transparent conductive electrodes (TCEs) for a variety of optoelectronic applications, but there have been no attempts to precisely control the percolation networks of AgNWs that critically affect the performances of TCEs. Here, we introduce a capillary printing technique to precisely control the NW alignment and the percolation behavior of AgNW networks. Notably, partially aligned AgNW networks exhibit a greatly lower percolation threshold, which leads to the substantial improvement of optical transmittance (96.7%) at a similar sheet resistance (19.5 Omega sq(-1)) as compared to random AgNW networks (92.9%, 20 Omega sq(-1)). Polymer light-emitting diodes (PLEDs) using aligned AgNW electrodes show a 30% enhanced maximum luminance (33068 cd m(-2)) compared to that with random AgNWs and a high luminance efficiency (14.25 cd A(-1)), which is the highest value reported so far using indium-free transparent electrodes for fluorescent PLEDs. In addition, polymer solar cells (PSCs) using aligned AgNW electrodes exhibit a power conversion efficiency (PCE) of 8.57%, the highest value ever reported to date for PSCs using AgNW electrodes. PMID- 26540013 TI - A Metal-Free Supercapacitor Electrode Material with a Record High Volumetric Capacitance over 800 F cm(-3). AB - A metal-free supercapacitor electrode material is prepared by the hybridization of graphene and polyaniline in a very compact way without sacrificing their gravimetric capacitance. It exhibits a record high volumetric capacitance over 800 F cm(-3). PMID- 26540012 TI - Phenotype of Spirometric Impairment in an Aging Population. AB - RATIONALE: The Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated. OBJECTIVES: To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment. METHODS: In COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, >=2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, >=25), poor exercise performance (6-minute-walk distance, <391 m), bronchodilator reversibility (FEV1 change, >12% and >=200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively). MEASUREMENTS AND MAIN RESULTS: GLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33 1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42]). CONCLUSIONS: GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes. PMID- 26540014 TI - Automatic periodic stimulation of the vagus nerve during single-incision transaxillary robotic thyroidectomy: Feasibility, safety, and first cases. AB - BACKGROUND: Automatic periodic stimulation (APS) of the vagus nerve during thyroid surgery may provide the patient with increased safety to prevent impending thermal or stretch-related injury to the recurrent laryngeal nerve (RLN). METHODS: Vagal stimulation would be of particular interest in remote access robotic thyroid surgery, where the RLN may be exposed to more conducted heat because of the exclusive use of the Harmonic scalpel. Using APS, the console surgeon may adjust the dissection technique according to the signal changes to avoid impending thermal damage to the nerve. RESULTS: In 2 transaxillary robotic thyroidectomy cases, we placed the vagus electrode onto the ipsilateral vagus trunk through the single-incision transaxillary access before docking the da Vinci robot. APS of the ipsilateral nerve has been conducted without complications. CONCLUSION: APS of the ipsilateral vagus is feasible and safe during transaxillary robotic thyroidectomy, and may contribute to prevent impending thermal injury to the RLN. PMID- 26540015 TI - An evaluation of the impact of 'Lifeskills' training on road safety, substance use and hospital attendance in adolescence. AB - PURPOSE: To evaluate if attendance at Lifeskills, a safety education centre for children in Year 6 (10-11 years), is associated with engagement in safer behaviours, and with fewer accidents and injuries, in adolescence. METHODS: The sample are participants in the Avon Longitudinal Study of Parents and Children who attended school in the Lifeskills catchment area in Year 6; 60% attended Lifeskills. At 14-15 years, participants (n approximately 3000, varies by outcome) self-reported road safety behaviours and accidents, and perceived health effects and use of alcohol, cannabis, and tobacco. Additional outcomes from linkage to Hospital Episodes Statistics were available for a sub-sample (n=1768): hospital admittance (for accident-related reason, from 11-16 years) and A&E attendance (for any reason, from approximately 14-16 years). RESULTS: Children who attended Lifeskills were more likely to report using pedestrian crossings on their way to school than children who did not attend (59% versus 52%). Lifeskills attendance was unrelated to the ownership of cycle helmets, or the use of cycle helmets, seat belts, or reflective/fluorescent clothing, or to A&E attendance. Use of cycle helmets (37%) and reflective/fluorescent clothing (<4%) on last cycle was low irrespective of Lifeskills attendance. Lifeskills attendance was associated with less reported smoking and cannabis use, but was generally unrelated to perceptions of the health impact of substance use. CONCLUSIONS: Lifeskills attendance was associated with some safer behaviours in adolescence. The overall low use of cycle helmets and reflective/fluorescent clothing evidences the need for powerful promotion of some safer behaviours at Lifeskills and at follow-up in schools. PMID- 26540016 TI - Sensitivity analyses for partially observed recurrent event data. AB - Recurrent events involve the occurrences of the same type of event repeatedly over time and are commonly encountered in longitudinal studies. Examples include seizures in epileptic studies or occurrence of cancer tumors. In such studies, interest lies in the number of events that occur over a fixed period of time. One considerable challenge in analyzing such data arises when a large proportion of patients discontinues before the end of the study, for example, because of adverse events, leading to partially observed data. In this situation, data are often modeled using a negative binomial distribution with time-in-study as offset. Such an analysis assumes that data are missing at random (MAR). As we cannot test the adequacy of MAR, sensitivity analyses that assess the robustness of conclusions across a range of different assumptions need to be performed. Sophisticated sensitivity analyses for continuous data are being frequently performed. However, this is less the case for recurrent event or count data. We will present a flexible approach to perform clinically interpretable sensitivity analyses for recurrent event data. Our approach fits into the framework of reference-based imputations, where information from reference arms can be borrowed to impute post-discontinuation data. Different assumptions about the future behavior of dropouts dependent on reasons for dropout and received treatment can be made. The imputation model is based on a flexible model that allows for time-varying baseline intensities. We assess the performance in a simulation study and provide an illustration with a clinical trial in patients who suffer from bladder cancer. PMID- 26540017 TI - Curcumin improves tendon healing in rats: a histological, biochemical, and functional evaluation. AB - Curcumin, a compound extracted from the roots of Zingiberaceae, has been proposed as a treatment for tissue injury but studies are yet to be done on its effect on tendon healing. Therefore, we performed a series of experiments to test our hypothesis that curcumin has positive effects on tendon repair. Patellar tendon window defect was created in Sprague-Dawley rats and these were divided into two groups: (i) control and (ii) curcumin-treated. Curcumin (100 mg/kg body weight) was applied by oral gavage. Its potential for promoting tendon healing was assessed by histological evaluation, mRNA expression of tenocyte-related genes, malondialdehyde (MDA) levels, manganese-dependent superoxide dismutase (MnSOD) activity, quantification of hydroxyproline (HOPro), and biomechanical testing. In this tendon injury model, curcumin significantly improved the healing properties as evidenced by extensive deposition of well-organized collagen fibers, decreased MDA levels, and increase in the biomechanical properties and MnSOD activity of the regenerated tendon tissues. The current study showed that curcumin can improve the quality of tendon rupture healing, and thus represents a promising strategy in the management of injured tendon tissue. PMID- 26540019 TI - Cytotoxic oplopane sesquiterpenoids from Arnoglossum atriplicifolium. AB - Pale Indian plantain (Arnoglossum atriplicifolium (L.) H. Rob.) is a plant with traditional medicinal usage among the Cherokee Native American tribe for treating cancer. Two oplopane sesquiterpenoids were isolated from an extract of A. atriplicifolium from Western North Carolina. The compounds were isolated by bioassay-guided fractionation using an MCF-7 breast tumour cell line assay. The known compound (1S,6R,7R,8R)-1-acetoxy-6,7-diangeloxy-8,10-epoxy-2-oxo-oplopa 3,14Z,11,12-dien-13-al (1) had an EC50 value of 9.0 MUM against MCF-7 cells, while the new compound (1S,3R,6R,7R,8R,11S)-1-acetoxy-6,7-diangeloxy-8,10,11,13 bisepoxyoplopan-2-one (2) had an EC50 value of 96 MUM. The compounds were characterised by 1D and 2D NMR spectroscopy and by comparison with literature values in the case for 1. Based on NOESY analysis, a correction of the relative configuration for 1 is presented. The presence of these compounds may help to explain the folk remedy usage of this plant as an anticancer agent. PMID- 26540018 TI - Two novel regulators of N-acetyl-galactosamine utilization pathway and distinct roles in bacterial infections. AB - Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d-galactosamine (GalN)/N acetyl-d-galactosamine (GalNAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/GalNAc catabolism pathway. The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA-seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes. Removal of agaR2 (not agaR1) from Streptococcus suis 05ZYH33 augments significantly the abilities of both adherence to Hep-2 cells and anti-phagocytosis against RAW264.7 macrophage. As anticipated, the dysfunction in AgaR2-mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets. Our finding discovered two novel regulators specific for GalN/GalNAc catabolism and assigned them distinct roles into bacterial infections. To the best of our knowledge, it might represent a first paradigm that links the GalN/GalNAc catabolism pathway to bacterial pathogenesis. PMID- 26540020 TI - Early diagnosis based on clinical history and BALF for successful management of smoking-induced acute eosinophilic pneumonia without unnecessary antibiotic usage: a case report. AB - INTRODUCTION: Acute eosinophilic pneumonia (AEP) is a rapid onset and severe respiratory illness characterized by acute febrile respiratory insufficiency, eosinophilic infiltration in the lungs and unique findings on chest imaging. Difficulty in differentiating from other respiratory distress caused by community acquired pneumonia may result in a delayed diagnosis or treatment with empirical antibiotics. CASE STUDY: Sixteen-year-old boy who developed AEP with marked eosinophilia in bronchoalveolar lavage fluid (BALF, 36.6%), decreased diffusion capacity of the lung for carbon monoxide (62%) and unique radiological findings. Although he initially denied tobacco use, on repeated thorough clinical history questioning, he eventually admitted beginning smoking 19 days before the onset of symptoms with gradually increasing frequency. RESULTS: His symptoms resolved quickly without use of antibiotics after cessation of tobacco and treatment with corticosteroids. CONCLUSION: Careful clinical history taking regarding tobacco use combined with early examination of BALF and recognition of unique radiological findings are critical for proper management of AEP. PMID- 26540021 TI - Injectable Self-Healing Glucose-Responsive Hydrogels with pH-Regulated Mechanical Properties. AB - Dynamically restructuring pH-responsive hydrogels are synthesized, employing dynamic covalent chemistry between phenylboronic acid and cis-diol modified poly(ethylene glycol) macromonomers. These gels display shear-thinning behavior, followed by a rapid structural recovery (self-healing). Size-dependent in vitro controlled and glucose-responsive release of proteins from the hydrogel network, as well as the biocompatibility of the gels, are evaluated both in vitro and in vivo. PMID- 26540022 TI - Complete maternal mitochondrial genome of freshwater mussel Aculamprotula tientsinensis (Bivalvia: Unionidae: Unioninae). AB - Aculamprotula tientsinensis is a rare and endemic species of freshwater mussel in China. This study firstly determined the complete F-type mitochondrial genome of A. tientsinensis. The circle genome (15 695 bp) comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, 1 FORF gene. Except for cob, nad5 and nad6, the remaining protein-coding genes initiate with the orthodox start codon (ATG, ATA, ATT). There are 26 non-coding regions in the mitogenome of A. tientsinensis, ranging in size from 1 to 229 bp. The base composition of the genome is A (37.83%), G (12.69%), T (25.43%) and C (24.06%). Gene order is identical to other female species of Unionidae but for Gonideinae. The phylogenetic analyses of Unionidae indicate that A. tientsinensis is closely related to A. tortuosa and A. coreana, which belong to Unioninae. The complete mitogenome can deepen comparative and evolutionary genomics of Unionidae and be more comprehensive to parse the genetic relationship between the species and the ownership beyond species. PMID- 26540023 TI - Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis. AB - A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein. PMID- 26540024 TI - Bench Press Upper-Body Muscle Activation Between Stable and Unstable Loads. AB - The bench press is one of the most commonly used upper-body exercises in training and is performed with many different variations, including unstable loads (ULs). Although there is much research on use of an unstable surface, there is little to none on the use of an UL. The purpose of this study was to investigate muscle activation during the bench press while using a stable load (SL) vs. UL. Twenty resistance-trained men (age = 24.1 +/- 2 years; ht = 177.5 +/- 5.8 cm; mass = 88.7 +/- 13.7 kg) completed 2 experimental conditions (SL and UL) at 2 different intensities (60 and 80% one repetition maximum). Unstable load was achieved by hanging 16 kg kettlebells by elastic bands from the end of the bar. All trial lifts were set to a 2-second cadence with a slight pause at the bottom. Subjects had electrodes attached to 5 muscles (pectoralis major, anterior deltoid, medial deltoid, triceps brachii, and latissimus dorsi) and performed 3 isometric bench press trials to normalize electromyographic data. All 5 muscles demonstrated significantly greater activation at 80% compared with 60% load and during concentric compared with eccentric actions. These results suggest that upper body muscle activation is not different in the bench press between UL and SL. Therefore, coaches should use their preference when designing training programs. PMID- 26540025 TI - Diagnosis of Pediatric Obstructive Sleep Apnea Syndrome in Settings With Limited Resources. AB - IMPORTANCE: Although polysomnographic (PSG) testing is the gold standard for the diagnosis of obstructive sleep apnea syndrome (OSAS) in children, the number of pediatric sleep laboratories is limited. Developing new screening methods for identifying OSAS may reduce the need for PSG testing. OBJECTIVE: To evaluate the combined use of the sleep clinical record (SCR) and nocturnal oximetry testing for predicting PSG results in children with clinically suspected OSAS. DESIGN, SETTING, AND PARTICIPANTS: Prospective study over 10 months. A cohort of 268 consecutive children (mean [SD], age 6 [3] years) referred for clinically suspected OSAS was studied at a pediatric sleep center at a university hospital. Children with disorders other than adenotonsillar hypertrophy or obesity were excluded. MAIN OUTCOMES AND MEASURES: Mild OSAS (obstructive apnea-hypopnea index [AHI], 1-5 episodes/h) and moderate-to-severe OSAS (AHI, >5 episodes/h) were the main outcome measures. Sleep clinical record scores greater than or equal to6.5 were considered positive, as were McGill oximetry scores (MOS) greater than 1, and these positive scores were the main explanatory variables in our study. Each participant was evaluated by the SCR, followed by pulse oximetry test the first night and PSG test in the sleep laboratory the second night. RESULTS: Of the total participants, 236 (88.1%) were diagnosed with OSAS, 236 (88.1%) had a positive SCR score, and 50 (18.7%) had a positive MOS. Participants with positive SCR scores had significantly increased risk of an AHI greater than or equal to 1 (adjusted odds ratio [AOR], 9.3; 95% CI, 3.7-23.2; P < .001). Children with an MOS greater than 1 were significantly more likely to have an AHI greater than 5 episodes/h than children with an MOS equal to 1 (AOR, 26.5; 95% CI, 7.8-89.2; P < .001). A positive SCR score had satisfactory sensitivity (91.9%) and positive predictive value (91.9%) but limited specificity (40.6%) and negative predictive value (40.6%) for OSAS. An MOS greater than 1 had excellent specificity (97.4%) and positive predictive value (94%) but low sensitivity (39.2%) and fair negative predictive value (60.8%) for moderate-to-severe OSAS among children with a positive SCR score. The combination of SCR scores and MOS correctly predicted primary snoring, mild OSAS, or moderate-to-severe OSAS in 154 of 268 (57.4%) participants. CONCLUSIONS AND RELEVANCE: The combined use of the SCR score and nocturnal oximetry results has moderate success in predicting sleep-disordered breathing severity when PSG testing is not an option. PMID- 26540026 TI - Physical Fitness in Adolescence and Subsequent Inflammatory Bowel Disease Risk. AB - OBJECTIVES: Physical fitness may reduce systemic inflammation levels relevant to the risk of symptomatic Crohn's disease (CD) and ulcerative colitis (UC); we assessed if fitness in adolescence is associated with subsequent inflammatory bowel disease (IBD) risk, independent of markers of risk and prodromal disease activity. METHODS: Swedish registers provided information on a cohort of 240,984 men (after exclusions) who underwent military conscription assessments in late adolescence (1969-1976). Follow-up started at least 4 years after the conscription assessment until 31 December 2009 (up to age 57 years). Cox's regression assessed the association of physical fitness with CD (n=986) and UC (n=1,878) in separate models, with adjustment including: socioeconomic conditions in childhood; physical fitness, height, body mass index, and erythrocyte sedimentation rate (ESR) in adolescence; and subsequent diagnoses of IBD. RESULTS: Low fitness was associated with a raised risk of IBD, with unadjusted hazard ratios (and 95% confidence intervals) of 1.62 (1.31-2.00) for CD and 1.36 (1.17-1.59) for UC. The results were attenuated by adjustment, particularly for markers of prodromal disease activity to 1.32 (1.05-1.66) and 1.25 (1.06-1.48), respectively. Raised ESR in adolescence was associated with increased risks for subsequent CD (5.95 (4.47-7.92)) and UC (1.92 (1.46-2.52)). CONCLUSIONS: The inverse association of physical fitness with IBD risk is consistent with a protective role for exercise. However, evidence of disease activity before diagnosis was already present in adolescence, suggesting that some or all of the association between fitness and IBD may be due to prodromal disease activity reducing exercise capacity and therefore fitness. PMID- 26540027 TI - Creation of an Electronic Data Repository for Patients With Nasal Obstruction Undergoing Functional Rhinoplasty. PMID- 26540029 TI - Immunotherapy in hepatocellular carcinoma: Primed to make a difference? AB - Advanced hepatocellular carcinoma (HCC) carries a dismal prognosis and the current treatment is limited to sorafenib, an agent with modest benefit. Preclinical data have indicated that several immunologic mechanisms are at play to promote HCC development and growth while impairing effective antitumor immune surveillance. Several novel approaches geared toward manipulating the immune response to HCC have suggested a therapeutic benefit in early-stage clinical trials, indicating a real potential to augment tumor-specific immunity and improve outcomes in patients with this disease. In the current study, the authors reviewed the barriers to an effective immune response against HCC and contemporary clinical investigations that may be "primed" to alter the natural history of HCC. PMID- 26540028 TI - Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial. AB - IMPORTANCE: Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE: To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN: The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH positive patients. INTERVENTIONS: Oral erlotinib treatment (150 mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES: Oral cancer-free survival (CFS). RESULTS: A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE: In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402779. PMID- 26540030 TI - Chemotaxonomic Metabolite Profiling of 62 Indigenous Plant Species and Its Correlation with Bioactivities. AB - Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on their phylogenetic family, in particular, Aceraceae, Betulaceae, and Fagaceae were distinguished from Rosaceae, Fabaceae, and Asteraceae. Quinic acid, gallic acid, quercetin, quercetin derivatives, kaempferol, and kaempferol derivatives were identified as family-specific metabolites, and were found in relatively high concentrations in Aceraceae, Betulaceae, and Fagaceae. Fagaceae and Asteraceae were selected based on results of PLS-DA and bioactivities to determine the correlation between metabolic differences among plant families and bioactivities. Quinic acid, quercetin, kaempferol, quercetin derivatives, and kaempferol derivatives were found in higher concentrations in Fagaceae than in Asteraceae, and were positively correlated with antioxidant and tyrosinase inhibition activities. These results suggest that metabolite profiling was a useful tool for finding the different metabolic states of each plant family and understanding the correlation between metabolites and bioactivities in accordance with plant family. PMID- 26540031 TI - Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment. AB - The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti influenza drug screening and discovery. PMID- 26540032 TI - Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury. AB - Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL 6, IL-12, TNF-alpha and IFN-gamma cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IkappaB-alpha, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-kappaB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing. PMID- 26540033 TI - Optimization of Extraction Condition of Bee Pollen Using Response Surface Methodology: Correlation between Anti-Melanogenesis, Antioxidant Activity, and Phenolic Content. AB - Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such as extraction solvent, extraction time, and extraction temperature, were optimized using response surface methodology. Regression analysis showed a good fit of this model and yielded the second-order polynomial regression for tyrosinase inhibition and antioxidant activity. Among the extraction variables, extraction solvent greatly affected the activity. The optimal condition was determined as EtOAc concentration in MeOH, 69.6%; temperature, 10.0 degrees C; and extraction time, 24.2 h, and the tyrosinase inhibitory and antioxidant activity under optimal condition were found to be 57.9% and 49.3%, respectively. Further analysis showed the close correlation between activities and phenolic content, which suggested phenolic compounds are active constituents of bee pollen for tyrosinase inhibition and antioxidant activity. Taken together, these results provide useful information about bee pollen as cosmetic therapeutics to reduce oxidative stress and hyperpigmentation. PMID- 26540034 TI - The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine. AB - Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines. PMID- 26540035 TI - Antihypertensive Effects of Artemisia scoparia Waldst in Spontaneously Hypertensive Rats and Identification of Angiotensin I Converting Enzyme Inhibitors. AB - We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4'-O-beta-D glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data. PMID- 26540036 TI - Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents. AB - In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4 triazoloquinoxalines. These compounds were synthesized via the reaction of the key intermediate hydrazinoquinoxalines with various reagents and evaluated for anticancer and antimicrobial activity. The results indicated that tetrazolo[1,5 a]quinoxaline derivatives showed the best result, with the highest inhibitory effects towards the three tested tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic to normal cells (IC50 values > 100 MUg/mL). Also, most of synthesized compounds exhibited the highest degrees of inhibition against the tested strains of Gram positive and negative bacteria, so tetrazolo[1,5-a]quinoxaline derivatives show dual activity as anticancer and antimicrobial agents. PMID- 26540037 TI - Anti-Inflammatory Activity Comparison among Scropoliosides-Catalpol Derivatives with 6-O-Substituted Cinnamyl Moieties. AB - We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-kappaB activity and IL-1beta expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then compared their anti-inflammatory activities against LPS induced NF-kappaB activity, cytokines mRNA expression, IL-1beta secretion, and cyclooxygenase-2 activity. The inhibitory effects of the scropoliosides varied depending on whether the 6-O-substituted cinnamyl moiety was linked to C'' 2-OH, C''3-OH, or C''4-OH, and on the number of moieties linked, which is closely related to the enhancement of antiinflammatory activity. Among these compounds, scropolioside B had the strongest antiinflammatory effects. PMID- 26540038 TI - Evaluation of New Fluorescent Lipophosphoramidates for Gene Transfer and Biodistribution Studies after Systemic Administration. AB - The objective of lung gene therapy is to reach the respiratory epithelial cells in order to deliver a functional nucleic acid sequence. To improve the synthetic carrier's efficacy, knowledge of their biodistribution and elimination pathways, as well as cellular barriers faced, depending on the administration route, is necessary. Indeed, the in vivo fate guides the adaptation of their chemical structure and formulation to increase their transfection capacity while maintaining their tolerance. With this goal, lipidic fluorescent probes were synthesized and formulated with cationic lipophosphoramidate KLN47 (KLN: Karine Le Ny). We found that such formulations present constant compaction properties and similar transfection results without inducing additional cytotoxicity. Next, biodistribution profiles of pegylated and unpegylated lipoplexes were compared after systemic injection in mice. Pegylation of complexes led to a prolonged circulation in the bloodstream, whereas their in vivo bioluminescent expression profiles were similar. Moreover, systemic administration of pegylated lipoplexes resulted in a transient liver toxicity. These results indicate that these new fluorescent compounds could be added into lipoplexes in small amounts without perturbing the transfection capacities of the formulations. Such additional properties allow exploration of the in vivo biodistribution profiles of synthetic carriers as well as the expression intensity of the reporter gene. PMID- 26540039 TI - Application of CRISPR/Cas9 Technology to HBV. AB - More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV. PMID- 26540041 TI - Comparison of Simple Eudragit Microparticles Loaded with Prednisolone and Eudragit-Coated Chitosan-Succinyl-Prednisolone Conjugate Microparticles: Part II. In Vivo Evaluation of Efficacy, Toxicity, and Biodisposition Characteristics. AB - We previously prepared and evaluated simple Eudragit S100 microparticles loaded with prednisolone (ES-MP) and Eudragit S100-coated chitosan-succinyl-prednisolone conjugate microparticles (Ch-MP/ES) in vitro. In this work, the effectiveness, toxic side effects (5 mg prednisolone (PD) eq/kg * 3 d, 10 mg PD eq/kg * 3 d), and pharmacokinetic characteristics (5 mg PD eq/kg) were examined using rats with colitis induced through 2,4,6-trinitrobenzenesulfonic acid. ES-MP did not change the efficacy or toxic side effects of PD, and this was attributed to incomplete delivery to the target site and prolonged systemic drug absorption by ES-MP. On the other hand, Ch-MP/ES promoted the efficacy of PD and ameliorated its toxic side effects due to better delivery to the target site, very slow drug release and the strong suppression of drug absorption. Only Ch-MP/ES, which markedly changed drug release characteristics, improved the in vivo features of PD. PMID- 26540042 TI - GHRH, PRP-PACAP and GHRHR Target Sequencing via an Ion Torrent Personal Genome Machine Reveals an Association with Growth in Orange-Spotted Grouper (Epinephelus coioides). AB - Growth hormone-releasing hormone (GHRH) and the receptor, GHRHR, constitute important components of the hypothalamus-pituitary growth axis and act on the downstream growth hormone (GH). PACAP-related peptide/pituitary adenylate cyclase activating polypeptide (PRP-PACAP) is a paralog of GHRH. These genes all play key roles in development and growth patterns. To improve the quality of cultured fish strains, natural genetic variation must be examined and understood. A mixed linear model has been widely used in association mapping, taking the population structures and pairwise kinship patterns into consideration. In this study, a mass cross population of orange-spotted grouper (Epinephelus coioides) was examined. These candidate genes were found to harbor low nucleotide diversity (thetaw from 0.00154 to 0.00388) and linkage disequilibrium levels (delay of 50% within 2 kbp). Association mapping was employed, and two single-nucleotide polymorphisms (KR269823.1:g.475A>C and KR269823.1:g.2143T>C) were found to be associated with growth (false discovery rate Q < 0.05), explaining 9.0%-17.0% of the phenotypic variance. The association of KR269823.1:g.2143T>C was also found via haplotype-based association (p < 0.05). The identified associations offer new insights into gene functions, and the associated single-nucleotide polymorphisms (SNPs) may be used for breeding purposes. PMID- 26540043 TI - Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress. AB - Endoplasmic reticulum (ER) stress is associated with the pathogenesis of hepatic steatosis. Alisma orientale Juzepzuk is a traditional medicinal herb for diuretics, diabetes, hepatitis, and inflammation. In this study, we investigated the protective effects of methanol extract of the tuber of Alisma orientale (MEAO) against ER stress-induced hepatic steatosis in vitro and in vivo. MEAO inhibited the tunicamycin-induced increase in luciferase activity of ER stress reporter constructs containing ER stress response element and ATF6 response element. MEAO significantly inhibited tunicamycin-induced ER stress marker expression including GRP78, CHOP, and XBP-1 in tunicamycin-treated Human hepatocellular carcinoma (HepG2) cells and the livers of tunicamycin-injected mice. It also inhibited tunicamycin-induced accumulation of cellular triglyceride. Similar observations were made under physiological ER stress conditions such as in palmitate (PA)-treated HepG2 cells and the livers of high fat diet (HFD)-induced obese mice. MEAO repressed hepatic lipogenic gene expression in PA-treated HepG2 cells and the livers of HFD obese mice. Furthermore, MEAO repressed very low-density lipoprotein receptor (VLDLR) expression and improved ApoB secretion in the livers of tunicamycin-injected mice or HFD obese mice as well as in tunicamycin or PA-treated HepG2 cells. Alismol, a guaiane-type sesquiterpenes in Alisma orientale, inhibited GRP78 expression in tunicamycin-treated HepG2 cells. In conclusion, MEAO attenuates ER stress and prevents hepatic steatosis pathogenesis via inhibition of expression of the hepatic lipogenic genes and VLDLR, and enhancement of ApoB secretion. PMID- 26540040 TI - The Role of Oxidative Stress and Antioxidants in Liver Diseases. AB - A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID- 26540044 TI - Homeodomain Protein Scr Regulates the Transcription of Genes Involved in Juvenile Hormone Biosynthesis in the Silkworm. AB - The silkworm Dominant trimolting (Moltinism, M3) mutant undergoes three larval molts and exhibits precocious metamorphosis. In this study, we found that compared with the wild-type (WT) that undergoes four larval molts, both the juvenile hormone (JH) concentration and the expression of the JH-responsive gene Kruppel homolog 1 (Kr-h1) began to be greater in the second instar of the M3 mutant. A positional cloning analysis revealed that only the homeodomain transcription factor gene Sex combs reduced (Scr) is located in the genomic region that is tightly linked to the M3 locus. The expression level of the Scr gene in the brain-corpora cardiaca-corpora allata (Br-CC-CA) complex, which controls the synthesis of JH, was very low in the final larval instar of both the M3 and WT larvae, and exhibited a positive correlation with JH titer changes. Importantly, luciferase reporter analysis and electrophoretic mobility shift assay (EMSA) demonstrated that the Scr protein could promote the transcription of genes involved in JH biosynthesis by directly binding to the cis-regulatory elements (CREs) of homeodomain protein on their promoters. These results conclude that the homeodomain protein Scr is transcriptionally involved in the regulation of JH biosynthesis in the silkworm. PMID- 26540045 TI - Myomaker, Regulated by MYOD, MYOG and miR-140-3p, Promotes Chicken Myoblast Fusion. AB - The fusion of myoblasts is an important step during skeletal muscle differentiation. A recent study in mice found that a transmembrane protein called Myomaker, which is specifically expressed in muscle, is critical for myoblast fusion. However, the cellular mechanism of its roles and the regulatory mechanism of its expression remain unclear. Chicken not only plays an important role in meat production but is also an ideal model organism for muscle development research. Here, we report that Myomaker is also essential for chicken myoblast fusion. Forced expression of Myomaker in chicken primary myoblasts promotes myoblast fusion, whereas knockdown of Myomaker by siRNA inhibits myoblast fusion. MYOD and MYOG, which belong to the family of myogenic regulatory factors, can bind to a conserved E-box located proximal to the Myomaker transcription start site and induce Myomaker transcription. Additionally, miR-140-3p can inhibit Myomaker expression and myoblast fusion, at least in part, by binding to the 3' UTR of Myomaker in vitro. These findings confirm the essential roles of Myomaker in avian myoblast fusion and show that MYOD, MYOG and miR-140-3p can regulate Myomaker expression. PMID- 26540046 TI - Characterization of Chitosan Nanofiber Sheets for Antifungal Application. AB - Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young's modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young's modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID- 26540047 TI - Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles. AB - The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO2, TiO2, ZnO, CuO, CeO2 and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters' size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. PMID- 26540048 TI - Construction of the High-Density Genetic Linkage Map and Chromosome Map of Large Yellow Croaker (Larimichthys crocea). AB - High-density genetic maps are essential for genome assembly, comparative genomic analysis and fine mapping of complex traits. In this study, 31,191 single nucleotide polymorphisms (SNPs) evenly distributed across the large yellow croaker (Larimichthys crocea) genome were identified using restriction-site associated DNA sequencing (RAD-seq). Among them, 10,150 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs). The total length of the genetic linkage map was 5451.3 cM with an average distance of 0.54 cM between loci. This represents the densest genetic map currently reported for large yellow croaker. Using 2889 SNPs to target specific scaffolds, we assigned 533 scaffolds, comprising 421.44 Mb (62.04%) of the large yellow croaker assembled sequence, to the 24 linkage groups. The mapped assembly scaffolds in large yellow croaker were used for genome synteny analyses against the stickleback (Gasterosteus aculeatus) and medaka (Oryzias latipes). Greater synteny was observed between large yellow croaker and stickleback. This supports the hypothesis that large yellow croaker is more closely related to stickleback than to medaka. Moreover, 1274 immunity related genes and 195 hypoxia-related genes were mapped to the 24 chromosomes of large yellow croaker. The integration of the high-resolution genetic map and the assembled sequence provides a valuable resource for fine mapping and positional cloning of quantitative trait loci associated with economically important traits in large yellow croaker. PMID- 26540049 TI - Betulinyl Sulfamates as Anticancer Agents and Radiosensitizers in Human Breast Cancer Cells. AB - Betulinic acid (BA), a natural compound of birch bark, is cytotoxic for many tumors. Recently, a betulinyl sulfamate was described that inhibits carbonic anhydrases (CA), such as CAIX, an attractive target for tumor-selective therapy strategies in hypoxic cancer cells. Data on combined CAIX inhibition with radiotherapy are rare. In the human breast cancer cell lines MDA-MB231 and MCF7, the effects of BA and betulinyl sulfamates on cellular and radiobiological behavior under normoxia and hypoxia were evaluated. The two most effective betulinyl sulfamates CAI 1 and CAI 3 demonstrated a 1.8-2.8-fold higher cytotoxicity than BA under normoxia in breast cancer cells, with IC50 values between 11.1 and 18.1 uM. BA exhibits its strongest cytotoxicity with IC50 values of 8.2 and 16.4 uM under hypoxia. All three substances show a dose-dependent increase in apoptosis, inhibition of migration, and inhibition of hypoxia-induced gene expression. In combination with irradiation, betulinyl sulfamates act as radiosensitizers, with DMF10 values of 1.47 (CAI 1) and 1.75 (CAI 3) under hypoxia in MDA-MB231 cells. BA showed additive effects in combination with irradiation. Taken together; our results suggest that BA and betulinyl sulfamates seem to be attractive substances to combine with radiotherapy; particularly for hypoxic breast cancer. PMID- 26540050 TI - Metagenomics: A New Way to Illustrate the Crosstalk between Infectious Diseases and Host Microbiome. AB - Microbes have co-evolved with human beings for millions of years. They play a very important role in maintaining the health of the host. With the advancement in next generation sequencing technology, the microbiome profiling in the host can be obtained under different circumstances. This review focuses on the current knowledge of the alteration of complex microbial communities upon the infection of different pathogens, such as human immunodeficiency virus, hepatitis B virus, influenza virus, and Mycobacterium tuberculosis, at different body sites. It is believed that the increased understanding of the correlation between infectious disease and the alteration of the microbiome can contribute to better management of disease progression in the future. However, future studies may need to be more integrative so as to establish the exact causality of diseases by analyzing the correlation between microorganisms within the human host and the pathogenesis of infectious diseases. PMID- 26540051 TI - Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells. AB - Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of gammaH2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID- 26540052 TI - Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing. AB - The Notch signaling pathway orchestrates cell fate by either inducing cell differentiation or maintaining cells in an undifferentiated state. This study aims to evaluate Notch expression and function in normal human keratinocytes. Notch1 is expressed in all epidermal layers, though to a different degree of intensity, with a dramatic decrease during ageing. Notch1 intracellular domain (N1ICD) levels are decreased during transit from keratinocyte stem cells (KSC) to transit amplifying (TA) cells, mimicking survivin expression in samples from donors of all ages. Calcium markedly reduces N1ICD levels in keratinocytes. N1ICD overexpression induces the up-regulation of survivin and the down-regulation of keratin 10 and involucrin, while increasing the S phase of the cell cycle. On the other hand, Notch1 inhibition (DAPT) dose-dependently decreases survivin, stimulates differentiation, and reduces keratinocyte proliferation in samples from donors of all ages. Silencing Notch downgrades survivin and increases keratin 10. In addition, Notch1 inhibition decreases survivin levels and proliferation both in KSC and TA cells. Finally, while survivin overexpression decreases keratinocyte differentiation and increases N1ICD expression both in KSC and TA cells, silencing survivin results in N1ICD down-regulation and an increase in differentiation markers. These results suggest that the Notch1/survivin crosstalk contributes to the maintenance of stemness in human keratinocytes. PMID- 26540053 TI - Computational Prediction of RNA-Binding Proteins and Binding Sites. AB - Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%-8% of all proteins are RNA-binding proteins (RBPs). Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein-RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein-RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions. PMID- 26540055 TI - Multi-UAV Routing for Area Coverage and Remote Sensing with Minimum Time. AB - This paper presents a solution for the problem of minimum time coverage of ground areas using a group of unmanned air vehicles (UAVs) equipped with image sensors. The solution is divided into two parts: (i) the task modeling as a graph whose vertices are geographic coordinates determined in such a way that a single UAV would cover the area in minimum time; and (ii) the solution of a mixed integer linear programming problem, formulated according to the graph variables defined in the first part, to route the team of UAVs over the area. The main contribution of the proposed methodology, when compared with the traditional vehicle routing problem's (VRP) solutions, is the fact that our method solves some practical problems only encountered during the execution of the task with actual UAVs. In this line, one of the main contributions of the paper is that the number of UAVs used to cover the area is automatically selected by solving the optimization problem. The number of UAVs is influenced by the vehicles' maximum flight time and by the setup time, which is the time needed to prepare and launch a UAV. To illustrate the methodology, the paper presents experimental results obtained with two hand-launched, fixed-wing UAVs. PMID- 26540054 TI - Abeta1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif. AB - The Amyloid-beta (Abeta)-derived, sphingolipid binding domain (SBD) peptide is a fluorescently tagged probe used to trace the diffusion behavior of sphingolipid containing microdomains in cell membranes through binding to a constellation of glycosphingolipids, sphingomyelin, and cholesterol. However, the molecular details of the binding mechanism between SBD and plasma membrane domains remain unclear. Here, to investigate how the peptide recognizes the lipid surface at an atomically detailed level, SBD peptides in the environment of raft-like bilayers were examined in micro-seconds-long molecular dynamics simulations. We found that SBD adopted a coil-helix-coil structural motif, which binds to multiple GT1b gangliosides via salt bridges and CH-pi interactions. Our simulation results demonstrate that the CH-pi and electrostatic forces between SBD monomers and GT1b gangliosides clusters are the main driving forces in the binding process. The presence of the fluorescent dye and linker molecules do not change the binding mechanism of SBD probes with gangliosides, which involves the helix-turn-helix structural motif that was suggested to constitute a glycolipid binding domain common to some sphingolipid interacting proteins, including HIV gp120, prion, and Abeta. PMID- 26540056 TI - Electronic Nose Feature Extraction Methods: A Review. AB - Many research groups in academia and industry are focusing on the performance improvement of electronic nose (E-nose) systems mainly involving three optimizations, which are sensitive material selection and sensor array optimization, enhanced feature extraction methods and pattern recognition method selection. For a specific application, the feature extraction method is a basic part of these three optimizations and a key point in E-nose system performance improvement. The aim of a feature extraction method is to extract robust information from the sensor response with less redundancy to ensure the effectiveness of the subsequent pattern recognition algorithm. Many kinds of feature extraction methods have been used in E-nose applications, such as extraction from the original response curves, curve fitting parameters, transform domains, phase space (PS) and dynamic moments (DM), parallel factor analysis (PARAFAC), energy vector (EV), power density spectrum (PSD), window time slicing (WTS) and moving window time slicing (MWTS), moving window function capture (MWFC), etc. The object of this review is to provide a summary of the various feature extraction methods used in E-noses in recent years, as well as to give some suggestions and new inspiration to propose more effective feature extraction methods for the development of E-nose technology. PMID- 26540057 TI - Active-Optical Sensors Using Red NDVI Compared to Red Edge NDVI for Prediction of Corn Grain Yield in North Dakota, U.S.A. AB - Active-optical sensor readings from an N non-limiting area standard established within a farm field are used to predict yield in the standard. Lower yield predictions from sensor readings obtained from other parts of the field outside of the N non-limiting standard area indicate a need for supplemental N. Active optical sensor algorithms for predicting corn (Zea mays, L.) yield to direct in season nitrogen (N) fertilization in corn utilize red NDVI (normalized differential vegetative index). Use of red edge NDVI might improve corn yield prediction at later growth stages when corn leaves cover the inter-row space resulting in "saturation" of red NDVI readings. The purpose of this study was to determine whether the use of red edge NDVI in two active-optical sensors (GreenSeekerTM and Holland Scientific Crop CircleTM) improved corn yield prediction. Nitrogen rate experiments were established at 15 sites in North Dakota (ND). Sensor readings were conducted at V6 and V12 corn. Red NDVI and red edge NDVI were similar in the relationship of readings with yield at V6. At V12, the red edge NDVI was superior to the red NDVI in most comparisons, indicating that it would be most useful in developing late-season N application algorithms. PMID- 26540058 TI - Determination of the Mineral Composition and Toxic Element Contents of Propolis by Near Infrared Spectroscopy. AB - The potential of near infrared spectroscopy (NIR) with remote reflectance fiber optic probes for determining the mineral composition of propolis was evaluated. This technology allows direct measurements without prior sample treatment. Ninety one samples of propolis were collected in Chile (Bio-Bio region) and Spain (Castilla-Leon and Galicia regions). The minerals measured were aluminum, calcium, iron, potassium, magnesium, phosphorus, and some potentially toxic trace elements such as zinc, chromium, nickel, copper and lead. The modified partial least squares (MPLS) regression method was used to develop the NIR calibration model. The determination coefficient (R2) and root mean square error of prediction (RMSEP) obtained for aluminum (0.79, 53), calcium (0.83, 94), iron (0.69, 134) potassium (0.95, 117), magnesium (0.70, 99), phosphorus (0.94, 24) zinc (0.87, 10) chromium (0.48, 0.6) nickel (0.52, 0.7) copper (0.64, 0.9) and lead (0.70, 2) in ppm. The results demonstrated that the capacity for prediction can be considered good for wide ranges of potassium, phosphorus and zinc concentrations, and acceptable for aluminum, calcium, magnesium, iron and lead. This indicated that the NIR method is comparable to chemical methods. The method is of interest in the rapid prediction of potentially toxic elements in propolis before consumption. PMID- 26540059 TI - A Novel Characteristic Frequency Bands Extraction Method for Automatic Bearing Fault Diagnosis Based on Hilbert Huang Transform. AB - Because roller element bearings (REBs) failures cause unexpected machinery breakdowns, their fault diagnosis has attracted considerable research attention. Established fault feature extraction methods focus on statistical characteristics of the vibration signal, which is an approach that loses sight of the continuous waveform features. Considering this weakness, this article proposes a novel feature extraction method for frequency bands, named Window Marginal Spectrum Clustering (WMSC) to select salient features from the marginal spectrum of vibration signals by Hilbert-Huang Transform (HHT). In WMSC, a sliding window is used to divide an entire HHT marginal spectrum (HMS) into window spectrums, following which Rand Index (RI) criterion of clustering method is used to evaluate each window. The windows returning higher RI values are selected to construct characteristic frequency bands (CFBs). Next, a hybrid REBs fault diagnosis is constructed, termed by its elements, HHT-WMSC-SVM (support vector machines). The effectiveness of HHT-WMSC-SVM is validated by running series of experiments on REBs defect datasets from the Bearing Data Center of Case Western Reserve University (CWRU). The said test results evidence three major advantages of the novel method. First, the fault classification accuracy of the HHT-WMSC-SVM model is higher than that of HHT-SVM and ST-SVM, which is a method that combines statistical characteristics with SVM. Second, with Gauss white noise added to the original REBs defect dataset, the HHT-WMSC-SVM model maintains high classification accuracy, while the classification accuracy of ST-SVM and HHT-SVM models are significantly reduced. Third, fault classification accuracy by HHT WMSC-SVM can exceed 95% under a Pmin range of 500-800 and a m range of 50-300 for REBs defect dataset, adding Gauss white noise at Signal Noise Ratio (SNR) = 5. Experimental results indicate that the proposed WMSC method yields a high REBs fault classification accuracy and a good performance in Gauss white noise reduction. PMID- 26540060 TI - A Spiking Neural Network in sEMG Feature Extraction. AB - We have developed a novel algorithm for sEMG feature extraction and classification. It is based on a hybrid network composed of spiking and artificial neurons. The spiking neuron layer with mutual inhibition was assigned as feature extractor. We demonstrate that the classification accuracy of the proposed model could reach high values comparable with existing sEMG interface systems. Moreover, the algorithm sensibility for different sEMG collecting systems characteristics was estimated. Results showed rather equal accuracy, despite a significant sampling rate difference. The proposed algorithm was successfully tested for mobile robot control. PMID- 26540061 TI - High Resolution Viscosity Measurement by Thermal Noise Detection. AB - An interferometric method is implemented in order to accurately assess the thermal fluctuations of a micro-cantilever sensor in liquid environments. The power spectrum density (PSD) of thermal fluctuations together with Sader's model of the cantilever allow for the indirect measurement of the liquid viscosity with good accuracy. The good quality of the deflection signal and the characteristic low noise of the instrument allow for the detection and corrections of drawbacks due to both the cantilever shape irregularities and the uncertainties on the position of the laser spot at the fluctuating end of the cantilever. Variation of viscosity below 0:03mPa.s was detected with the alternative to achieve measurements with a volume as low as 50 uL. PMID- 26540062 TI - Surface Plasmon Resonance Sensor Based on Ethylene Tetra-Fluoro-Ethylene Hollow Fiber. AB - A new kind of hollow fiber surface plasmon resonance sensor (HF-SPRS) based on the silver-coated ethylene tetra-fluoro-ethylene (ETFE) hollow fiber (HF) is presented. The ETFE HF-SPRS is fabricated, and its performance is investigated experimentally by measuring the transmission spectra of the sensor when filled by liquid sensed media with different refractive indices (RIs). Theoretical analysis based on the ray transmission model is also taken to evaluate the sensor. Because the RI of ETFE is much lower than that of fused silica (FSG), the ETFE HF-SPRS can extend the lower limit of the detection range of the early reported FSG HF SPRS from 1.5 to 1.42 approximately. This could greatly enhance the application potential of HF-SPRS. Moreover, the joint use of both ETFE and FSG HF-SPRSs can cover a wide detection range from 1.42 to 1.69 approximately with high sensitivities larger than 1000 nm/RIU. PMID- 26540063 TI - Short-Term Impact of a Comprehensive Smoke-Free Law Following a Partial Smoke Free Law on PM2.5 Concentration Levels at Hospitality Venues on the Peripheries of College Campuses. AB - Tobacco-free policies on college campuses are spreading in Korea. However, the impact of the smoking ban legislation at venues on the boundary of a college campus is still limited. This study aimed to assess short-term changes in PM2.5 concentrations before and after the enactment of the smoking ban legislation to evaluate the impact. In this cross-sectional study, PM2.5 measurements (pre-ban: n = 99, post-ban: n = 64) were conducted in randomly selected billiards, pubs, and computer game rooms on the peripheries of college campuses in October 2013, prior to implementation of the smoking ban, and in May 2014, after the ban. The median (interquartile range, IQR) of the PM2.5 concentration for all venues was 31 MUg/m3 (0-80 MUg/m3) in the pre-ban period and 11 MUg/m3 (0-36 MUg/m3) in the post-ban period implying indoor PM2.5 concentration levels of the peripheries of college campuses likely decreased one year after implementation of the ban. However, the differences were not significant yet. The results support the introduction of more rigorous monitoring of SHS exposure levels toward the ultimate goal of encouraging a complete smoking ban in hospitality venues, including billiards, pubs, and computer game rooms located on the peripheries of college campuses. PMID- 26540064 TI - Ambulatory Care Visits to Pediatricians in Taiwan: A Nationwide Analysis. AB - Pediatricians play a key role in the healthy development of children. Nevertheless, the practice patterns of pediatricians have seldom been investigated. The current study analyzed the nationwide profiles of ambulatory visits to pediatricians in Taiwan, using the National Health Insurance Research Database. From a dataset that was randomly sampled one out of every 500 records among a total of 309,880,000 visits in 2012 in the country, 9.8% (n = 60,717) of the visits were found paid to pediatricians. Children and adolescents accounted for only 69.3% of the visits to pediatricians. Male pediatricians provided 80.5% of the services and the main workforces were those aged 40-49 years. The most frequent diagnoses were respiratory tract diseases (64.7%) and anti-histamine agents were prescribed in 48.8% of the visits to pediatricians. Our detailed results could contribute to evidence-based discussions on health policymaking. PMID- 26540065 TI - Disease Burden from Hepatitis B Virus Infection in Guangdong Province, China. AB - OBJECTIVE: To estimate the disease burden and financial burden attributed to hepatitis B virus (HBV) infection in Guangdong Province. METHODS: Based on the data of incidence, mortality and healthcare cost of HBV-related diseases and other socio-economic data in Guangdong Province, we estimated deaths, disability adjusted life-years (DALYs) and economic cost for the three HBV-related diseases hepatitis B, liver cirrhosis and liver cancer-in Guangdong following the procedures developed for the global burden of disease study. Then disease burden and economic cost attributed to HBV infection was estimated. RESULTS: HBV infection was estimated to have caused 33,600 (95% confidence interval (CI): 29,300-37,800) premature deaths and the loss of 583,200 (95% CI: 495,200-671,100) DALYs in Guangdong in 2005. The greatest loss of deaths and DALYs were from liver cancer. The 45-59 years age group had the greatest burden attributable to HBV infection. The estimated total annual cost of HBV-related diseases in Guangdong was RMB 10.8 (95% CI: 8.7-13.0) billion, the direct and indirect cost were RMB 2.6 (95% CI: 2.1-3.2) and 8.2 (95% CI: 6.6-9.8) billion. CONCLUSIONS: HBV infection is a great medical challenge as well as a significant economic burden to Guangdong Province. The results suggest that substantial health benefits could be gained by extending effective public health and clinical interventions to reduce HBV infection in Guangdong Province. PMID- 26540066 TI - Carotenoid Content in Organically Produced Wheat: Relevance for Human Nutritional Health on Consumption. AB - In this study, 33 spring and winter wheat genotypes were analyzed for carotenoid content and composition. Investigated genotypes were divided into four genotype groups i.e., spelt, landraces, old cultivars and primitive wheat. The results showed a high level of variation among the genotypes in amount of carotenoids in the grain with high values (around 4 mg/Kg) especially in one of the genotypes Oland 8. Lutein was the most common carotenoid in all the investigated genotypes, contributing 70%-90% of the carotenoids in the grain. Variation in carotenoid content and composition was found not only among genotypes, but also between genotype groups and wheat type, although there is a need to analyze more genotypes to confirm the differences found between groups and types. This study showed that 40% of the daily requirements of lutein can be achieved from the genotypes with the highest lutein content (Oland 8) produced using organic farming through the average human consumption of 200 grams of wheat per day. Furthermore, this study showed, by the use of principal component analyses, an opportunity to select genotypes combining high values of certain nutritional compounds. By a further breeding and commercial production of such genotypes, the nutritional value of wheat flour for human consumption can be improved. PMID- 26540067 TI - Health-Related Quality of Life of Former Lead Workers in Brazil. AB - Little is known about the health-related quality of life of former lead workers. Using the Short-Form 36 Questionnaire (SF-36), a cross-section design study evaluated the health-related quality of life of 186 former workers of a lead smelter that operated in Santo Amaro da Purificacao, Brazil, from 1960 to 1993, when it closed down. The smelter had very poor occupational and environmental hygiene standards. The health-related quality of life of former lead workers was low, compared to population-based and other nosological groups from Brazil. Former lead workers who indicated metal poisoning, difficulty getting another job and who could not get another job after dismissal by the smelter presented poorer health-related quality of life. Former lead workers with poor health-related quality of life form part of the huge occupational liability left by the Santo Amaro lead smelter. PMID- 26540068 TI - Trade-Off and Synergy among Ecosystem Services in the Guanzhong-Tianshui Economic Region of China. AB - Natural ecosystems provide society with important goods and services. With rapidly increasing populations and excessive utilization of natural resources, humans have been enhancing the production of some services at the expense of others. Although the need for certain trade-offs between conservation and development is urgent, having only a small number of efficient methods to assess such trade-offs has impeded progress. This study focuses on the evaluation of ecosystem services under different land use schemes. It reveals the spatial and temporal distributions of and changes in ecosystem services. Based on a correlation rate model and distribution mapping, the trade-offs and synergies of these ecosystem services can be found. Here, we also describe a new simple approach to quantify the relationships of every trade-off and synergy. The results show that all ecosystem services possess trade-offs and synergies in the study area. The trend of improving carbon sequestration and water interception indicate that these key ecosystem services have the strongest synergy. And the decrease in regional agricultural production and other services, except water yield, may be considered as trade-offs. The synergy between water yield and agricultural production was the most significant, while the trade-off between water interception and carbon sequestration was the most apparent, according to our interaction quantification model. The results of this study have implications for planning and monitoring the future management of natural capital and ecosystem services, and can be integrated into land use decision-making. PMID- 26540071 TI - Examining Means of Reaching Adolescent Girls for Iron Supplementation in Tigray, Northern Ethiopia. AB - BACKGROUND: Iron deficiency is the most prevalent nutritional deficiency in adolescent girls from the developing world. One of the recommended interventions to improve iron status in adolescent girls is iron supplementation. Yet the provision of iron supplements to adolescent girls proved to be a challenging task for the health systems across the developing world. OBJECTIVE: The objective of the study was to examine means of reaching adolescent girls for iron supplementation in Northern Ethiopia. METHODOLOGY: Analytical cross-sectional study consisting of both quantitative and qualitative approaches to data collection and analysis was used in this study. Stratified multi-stage systematic random sampling technique was adopted and primary quantitative data were collected from 828 (578 school attending and 250 non school attending) adolescent girls recruited from nine districts of Tigray. The primary quantitative data were analyzed using SPSS version 20 software. The qualitative data collected through key informant interviews and focus group discussions were transcribed verbatim and qualitatively analyzed. RESULTS: The mean (SD) age of the girls was 16.7 (1.4) years. Four hundred forty seven (54%), 355 (42.9%) and 26 (3.1%) of the adolescent girls had low, medium and high diet diversity scores, respectively. More than half, 467 (56%), of the adolescent girls believed that adolescent girls were overloaded with household jobs everyday compared to boys from their respective communities. Key informants said that, there is no adolescent nutrition message promoted in the study area. Low community awareness, perceiving iron tablet as a contraceptive, religious and cultural influences, and lack of confidence in supplementation value of iron tablets, are some of the potential barriers mentioned by the key informant and focus group discussion participants. Schools (45%), health centers (27%) and health posts (26%) were the preferred public facilities for provision of iron supplements to student adolescent girls whereas schools (11%), health centers (47%) and health posts (41%) were the preferred public facilities for provision of iron supplements to adolescent girls who were not attending schools from the study communities. CONCLUSION: The health posts and health centers were the preferred health facilities for iron supplementation to adolescent girls who were not attending schools while the school was the preferred facility for iron supplementation of student adolescent girls. PMID- 26540070 TI - Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age. AB - The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4-6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45-15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence-third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration-a surrogate marker for MID-was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10-15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children. PMID- 26540074 TI - Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala. AB - Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-alpha-L-rhamnopyranosyl-(1 -> 6)-beta-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 +/- 0.2 MUmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. PMID- 26540072 TI - Fermentation of Green Tea with 2% Aquilariae lignum Increases the Anti-Diabetic Activity of Green Tea Aqueous Extracts in the High Fat-Fed Mouse. AB - Anti-diabetic effects on the metabolomic differences between green tea (GT) and Aquilariae lignum-fermented green tea (fGT) were investigated in the high fat-fed mouse. To prove the differences, hypoglycemic (blood glucose, insulin and glycated hemoglobin levels, pancreas weights and histopathological immunohistochemistrical analysis of pancreas-insulin/glucagon cells), hepato- and nephron-protective (the changes in liver and kidney weight, histopathology of liver and kidney, serum aminotransferases (AST and ALT) levels, blood urea nitrogen, and serum creatinine levels), and hypolipidemic (the changes of serum total cholesterol, triglyceride, low- and high-density lipoprotein levels with fecal total cholesterol (TC) and triglyceride (TG) contents) effects were evaluated. In addition, liver lipid peroxidation, the glutathione contents, and catalase and superoxide dismutase activities were measured according to the hepatic glucose-regulating enzyme activities of glucokinase (GK), glucose-6 phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) for action mechanisms. As a result, fGT showed a stronger hypoglycemic, hepato- and nephron protective, hypolipidemic, and anti-oxidant effect than GT in high fat-fed mice. In addition, fGT-treated mice exerted more favorable inhibitory activities against GK, G6pase, PERCK activities as compared to GT-treated mice. Taken together, fGT fermented with Aquilariae lignum, 1:49 (2%; g/g) has a stronger effect compared with GT. Therefore, fGT has the potential to increase bioactivity against type 2 diabetics. PMID- 26540073 TI - Synergistic Effects of Human Milk Nutrients in the Support of Infant Recognition Memory: An Observational Study. AB - The aim was to explore the relation of human milk lutein; choline; and docosahexaenoic acid (DHA) with recognition memory abilities of six-month-olds. Milk samples obtained three to four months postpartum were analyzed for fatty acids, lutein, and choline. At six months, participants were invited to an electrophysiology session. Recognition memory was tested with a 70-30 oddball paradigm in a high-density 128-lead event-related potential (ERP) paradigm. Complete data were available for 55 participants. Data were averaged at six groupings (Frontal Right; Frontal Central; Frontal Left; Central; Midline; and Parietal) for latency to peak, peak amplitude, and mean amplitude. Difference scores were calculated as familiar minus novel. Final regression models revealed the lutein X free choline interaction was significant for the difference in latency scores at frontal and central areas (p < 0.05 and p < 0.001; respectively). Higher choline levels with higher lutein levels were related to better recognition memory. The DHA X free choline interaction was also significant for the difference in latency scores at frontal, central, and midline areas (p < 0.01; p < 0.001; p < 0.05 respectively). Higher choline with higher DHA was related to better recognition memory. Interactions between human milk nutrients appear important in predicting infant cognition, and there may be a benefit to specific nutrient combinations. PMID- 26540069 TI - Host-Targeting Agents to Prevent and Cure Hepatitis C Virus Infection. AB - Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) which are leading indications of liver transplantation (LT). To date, there is no vaccine to prevent HCV infection and LT is invariably followed by infection of the liver graft. Within the past years, direct-acting antivirals (DAAs) have had a major impact on the management of chronic hepatitis C, which has become a curable disease in the majority of DAA treated patients. In contrast to DAAs that target viral proteins, host-targeting agents (HTAs) interfere with cellular factors involved in the viral life cycle. By acting through a complementary mechanism of action and by exhibiting a generally higher barrier to resistance, HTAs offer a prospective option to prevent and treat viral resistance. Indeed, given their complementary mechanism of action, HTAs and DAAs can act in a synergistic manner to reduce viral loads. This review summarizes the different classes of HTAs against HCV infection that are in preclinical or clinical development and highlights their potential to prevent HCV infection, e.g., following LT, and to tailor combination treatments to cure chronic HCV infection. PMID- 26540075 TI - Complex Commingling: Nucleoporins and the Spindle Assembly Checkpoint. AB - The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC), which monitors the bipolar attachment of the mitotic spindle to chromosomes to prevent errors that would result in chromosome mis-segregation and aneuploidy. Multiple components of the nuclear pore complex (NPC), a gigantic protein complex that forms a channel through the nuclear envelope to allow nucleocytoplasmic exchange of macromolecules, were shown to be critical for faithful cell division and implicated in the regulation of different steps of the mitotic process, including kinetochore and spindle assembly as well as the SAC. In this review, we will describe current knowledge about the interconnection between the NPC and the SAC in an evolutional perspective, which primarily relies on the two mitotic checkpoint regulators, Mad1 and Mad2. We will further discuss the role of NPC constituents, the nucleoporins, in kinetochore and spindle assembly and the formation of the mitotic checkpoint complex during mitosis and interphase. PMID- 26540076 TI - Form, Fabric, and Function of a Flagellum-Associated Cytoskeletal Structure. AB - Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. A number of cytoskeletal structures are associated with the flagellum in T. brucei, and one such structure-a multiprotein complex containing the repeat motif protein TbMORN1-is the focus of this review. The TbMORN1-containing complex, which was discovered less than ten years ago, is essential for the viability of the mammalian-infective form of T. brucei. The complex has an unusual asymmetric morphology, and is coiled around the flagellum to form a hook shape. Proteomic analysis using the proximity-dependent biotin identification (BioID) technique has elucidated a number of its components. Recent work has uncovered a role for TbMORN1 in facilitating protein entry into the cell, thus providing a link between the cytoskeleton and the endomembrane system. This review summarises the extant data on the complex, highlights the outstanding questions for future enquiry, and provides speculation as to its possible role in a size-exclusion mechanism for regulating protein entry. The review additionally clarifies the nomenclature associated with this topic, and proposes the adoption of the term "hook complex" to replace the former name "bilobe" to describe the complex. PMID- 26540077 TI - Transcriptome Analysis of Two Vicia sativa Subspecies: Mining Molecular Markers to Enhance Genomic Resources for Vetch Improvement. AB - The vetch (Vicia sativa) is one of the most important annual forage legumes globally due to its multiple uses and high nutritional content. Despite these agronomical benefits, many drawbacks, including cyano-alanine toxin, has reduced the agronomic value of vetch varieties. Here, we used 454 technology to sequence the two V. sativa subspecies (ssp. sativa and ssp. nigra) to enrich functional information and genetic marker resources for the vetch research community. A total of 86,532 and 47,103 reads produced 35,202 and 18,808 unigenes with average lengths of 735 and 601 bp for V. sativa sativa and V. sativa nigra, respectively. Gene Ontology annotations and the cluster of orthologous gene classes were used to annotate the function of the Vicia transcriptomes. The Vicia transcriptome sequences were then mined for simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers. About 13% and 3% of the Vicia unigenes contained the putative SSR and SNP sequences, respectively. Among those SSRs, 100 were chosen for the validation and the polymorphism test using the Vicia germplasm set. Thus, our approach takes advantage of the utility of transcriptomic data to expedite a vetch breeding program. PMID- 26540078 TI - Update on Alcoholic Hepatitis. AB - Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID- 26540079 TI - The cost-effectiveness of short-term and long-term psychotherapy in the treatment of depressive and anxiety disorders during a 5-year follow-up. AB - Both short-term and long-term psychotherapies are used extensively in treating different mental disorders, but there have been practically no attempts to compare their cost-effectiveness. The aim of this study, which is part of the Helsinki Psychotherapy Study, is to assess the cost-effectiveness of two short term therapies compared to that of a long-term therapy. In this study 326 outpatients suffering from mood or anxiety disorder were randomized to solution focused therapy (SFT), short-term psychodynamic psychotherapy (SPP) or to long term psychodynamic psychotherapy (LPP). Psychiatric symptoms and working ability were assessed at baseline and then 4-9 times during a 5-year follow-up using eight widely used measures including e.g. Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), Symptom Check List, anxiety scale (SCL 90-Anx), Hamilton Anxiety Rating Scale (HARS), Symptom Check List, Global Severity Index (SCL-90-GSI), and the Work-subscale (SAS-Work) of the Social Adjustment Scale (SAS-SR). Both direct and indirect costs were measured. During the 5-year follow-up period statistically significant improvements were observed in all health indicators in all therapy groups. At first the recovery was faster in the short-term therapy groups than in the LPP group, but taking the whole follow-up period into account, the effectiveness of the LPP was somewhat greater than that of the short-term therapies. Especially the direct costs were, however, much higher in the LPP group than in the short-term therapy groups. Thus the long term therapy can hardly be regarded as cost-effective compared to short-term therapies when patients are randomized to the therapy groups. PMID- 26540080 TI - The prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis. AB - BACKGROUND: Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer's disease (AD). However, published data on the prevalence of NPS in persons with AD are conflicting. This meta-analysis aimed to estimate the prevalence of NPS in persons with AD. METHODS: Studies published from 1964 to September 30, 2014, were identified from PubMed and Embase database, reference lists and conference abstracts. We calculated prevalence rates and conducted meta-regression analysis with random-effects model, according to study characteristics, population demographics or condition information. RESULTS: We identified 48 eligible articles, which provided data for 12 NPS reported in Neuropsychiatric Inventory (NPI). The most frequent NPS was apathy, with an overall prevalence of 49% (95% CI 41-57%), followed by depression, aggression, anxiety and sleep disorder, the pooled prevalence estimates of which were 42% (95% CI 37-46%), 40% (95% CI 33-46%), 39% (95% CI 32-46%) and 39% (95% CI 30-47%), respectively. The less prevalent NPS were irritability (36%, 31-41%), appetite disorder (34%, 27-41%), aberrant motor behavior (32%, 25-38%), delusion (31%, 27-35%), disinhibition (17%, 12-21%) and hallucination (16%, 13-18%). Least common was euphoria, with an overall prevalence of 7% (95% CI 5-9%). LIMITATIONS: Several aspects, such as the quality of included studies were not always optimal and there was significant heterogeneity of prevalence estimate across studies. CONCLUSIONS: NPS were observed to be highly prevalent in AD patients. Disease duration, age, education level, population origin and the severity of cognitive impairment had influence on the prevalence of some NPS. PMID- 26540081 TI - Decreased serum zinc concentration during depressive episode in patients with bipolar disorder. AB - OBJECTIVES: Zinc may be involved in the pathophysiology and treatment of depressive disorder. However, data on this issue in bipolar disorder (BD) are limited. The aim of the study was to assess zinc concentrations in the blood serum of patients at various phases and stages of bipolar disorder. METHODS: The study included 129 patients with a diagnosis of bipolar disorder type I (n=69) or type II (n=60). Fifty-eight were in a depressive episode, 23 in a manic episode and 48 in remission. Fifty healthy volunteers made a control group. Zinc concentration was measured using flame atomic absorption spectrometry. RESULTS: Serum zinc level in patients diagnosed with BD type I in the depressive phase was significantly reduced as compared with mania, remission and healthy subjects. In the BD type II, serum zinc level in hypomania, depression or remission phase was not significantly different from the control group. In the whole group, lower level of zinc in depression compared to remission and control subjects was found during late stage of the illness but not in the early stage. Zinc concentration was not dependent on the severity of manic or depressive symptoms and subtype of depression but correlated positively with the number of manic/hypomanic relapses in the past year. LIMITATIONS: Lack of prospective model, heterogeneity of pharmacological treatment, small number of subgroups presenting specified clinical features. CONCLUSIONS: Decreased serum zinc concentration occurs in depression in BD type I and probably in depression in the late stage of BD. PMID- 26540082 TI - Re-experiencing phenomena following a disaster: The long-term predictive role of intrusion symptoms in the development of post-trauma depression and anxiety. AB - BACKGROUND: Contention in the literature regarding the diagnostic utility of intrusion symptoms highlights that they have high sensitivity but low specificity in predicting PTSD. They are highly prevalent following a range of traumatic events, and across a range of disorders. The prevalence of intrusion symptoms in the absence of PTSD suggests their relevance to the development of other psychopathology. Therefore, the predictive role of intrusion symptoms for other post-trauma psychopathology was examined using data from an epidemiological, longitudinal sample of adults recruited in childhood. METHOD: From 5 phases of data collection for this sample, these analyses focused on the 20 year and 28 year follow-ups (n=583). Lifetime exposure to trauma was assessed using a modified set of 10 Criterion-A events from the Composite International Diagnostic Interview (CIDI), with PTSD assessed in reference to a self-nominated worst lifetime event, and other DSM-IV disorder also assessed using the CIDI. RESULTS: Results showed that the presence of intrusion symptoms without PTSD at the 20 year follow-up was predictive of increased risk at 28 years for depressive but not anxiety disorders. LIMITATIONS: There was limited psychopathology in the sample, reducing the power to examine many individual disorders. Furthermore, trauma history and psychiatric symptoms were retrospectively reported, introducing the possibility of recall bias. CONCLUSION: Together the findings suggest that intrusion symptoms may play an aetiological role in the development and/or maintenance of disorders other than PTSD. PMID- 26540083 TI - Dalfampridine in chronic sensorimotor deficits after ischemic stroke: A proof of concept study. AB - OBJECTIVE: To evaluate the safety and tolerability of dalfampridine extended release (D-ER) in participants with chronic post-ischemic stroke deficits, and to assess for potential drug activity on sensorimotor function. METHODS: Using a double-blind, placebo-controlled, cross-over design, participants were randomized to placebo/D-ER or D-ER/placebo sequences and given D-ER 10 mg or placebo twice daily. Key inclusion criteria were: ischemic stroke >= 6 months, Fugl-Meyer Assessment lower extremity motor score <= 28, ability to complete Timed 25-Foot Walk (T25FW). The primary outcome was safety and tolerability. The key exploratory measure was walking speed (T25FW). Other assessments were: Box and Block, and Grip and Pinch tests; Functional Independence Measure. Full-crossover data were analyzed using mixed-effects model. RESULTS: A total of 83 participants were randomized: 70 completed and 13 discontinued the study. Adverse events were consistent with previous D-ER trials; no new safety signals were observed. Four participants experienced serious adverse events: 3 seizures (1 placebo, 2 D-ER), 1 was secondary to intentional overdose. Most common treatment-emergent adverse events were: dizziness, nausea, arthralgia and fatigue. Mixed-effects analysis showed an effect for D-ER vs. placebo in improving walking speed (0.21 vs. 0.10 ft/s; p = 0.027). CONCLUSIONS: D-ER was generally well tolerated in participants with chronic stroke deficits. Potential drug activity on lower extremity sensorimotor function, with an improvement in walking speed, was seen. PMID- 26540084 TI - Bisphenol A glucuronide deconjugation is a determining factor of fetal exposure to bisphenol A. AB - Previous studies in experimental animals have shown that maternal exposure to bisphenol A (BPA) during late pregnancy leads to high plasma concentrations of BPA glucuronide (BPAG) in fetus compared to mother due to the inability of BPAG to cross the placental barrier. A recent in vitro study has reported that BPAG can exert adipogenic effect underlining the need for characterization of the fetal disposition of BPAG. Experiments were conducted in chronically catheterized fetal sheep to determine the contribution of BPAG hydrolysis to BPA to the elimination of BPAG from the fetal compartment and its resulting effect on the overall fetal exposure to free BPA. Serial sampling of fetal arterial blood, amniotic fluid, maternal venous blood and urine was performed following separate single doses of BPA and BPAG administered intravenously to eight fetal/maternal pairs after cesarean section, and repeated BPAG doses given to two fetal sheep. On average 67% of the BPA entering the fetal circulation was rapidly eliminated through fetal to maternal clearance, with a very short half-life (20 min), while the remaining fraction (24%) was glucuronoconjugated. BPA conjugation deconjugation cycling was responsible for a 43% increase of the overall fetal exposure to free BPA. A very specific pattern of fetal exposure to free BPA was observed due to its highly increased persistence with a hydrolysis-dependent plasma terminal free BPA half-life of several tens of hours. These findings suggest that although the high fetal to maternal clearance of free BPA protects the fetus from transient increases in free BPA plasma concentrations associated with maternal BPA intake, low but sustained basal free BPA concentrations are maintained in the fetus through BPA conjugation-deconjugation cycling. The potential health implications of these low but sustained basal concentrations of free BPA in fetal plasma should be addressed especially when considering time dependent effects. PMID- 26540085 TI - Residential green spaces and mortality: A systematic review. AB - BACKGROUND: A number of studies have associated natural outdoor environments with reduced mortality but there is no systematic review synthesizing the evidence. OBJECTIVES: We aimed to systematically review the available evidence on the association between long-term exposure to residential green and blue spaces and mortality in adults, and make recommendations for further research. As a secondary aim, we also conducted meta-analyses to explore the magnitude of and heterogeneity in the risk estimates. METHODS: Following the PRISMA statement guidelines for reporting systematic reviews and meta-analysis, two independent reviewers searched studies using keywords related to natural outdoor environments and mortality. DISCUSSION: Our review identified twelve eligible studies conducted in North America, Europe, and Oceania with study populations ranging from 1645 up to more than 43 million individuals. These studies are heterogeneous in design, study population, green space assessment and covariate data.We found that the majority of studies show a reduction of the risk of cardiovascular disease (CVD) mortality in areas with higher residential greenness. Evidence of a reduction of all-cause mortality is more limited, and no benefits of residential greenness on lung cancer mortality are observed. There were no studies on blue spaces. CONCLUSIONS: This review supports the hypothesis that living in areas with higher amounts of green spaces reduces mortality, mainly CVD. Further studies such as cohort studies with more and better covariate data, improved green space assessment and accounting well for socioeconomic status are needed to provide further and more complete evidence, as well as studies evaluating the benefits of blue spaces. PMID- 26540086 TI - The influence of size on the toxicity of an encapsulated pesticide: a comparison of micron- and nano-sized capsules. AB - Encapsulation technology involves entrapping a chemical active ingredient (a.i.) inside a hollow polymeric shell and has been applied to commercial pesticide manufacturing for years to produce capsule suspension (CS) formulations with average particle sizes in the micron-scale. The few literature sources that investigate the environmental fate and toxicity to non-target organisms of encapsulated commercially available pesticide products with regard to capsule size report on average sizes between 20 and 50 MUm. Here, we have identified a CS formulation with an average capsule size of approximately 2 MUm with some capsules extending into the nanometer scale (~200 nm). Determining how carrier size influences toxicity is important to understanding if current pesticide risk assessments are sufficient to protect against products that incorporate encapsulation technology. Here, a commercial pyrethroid CS pesticide with lambda cyhalothrin (lambda-Cy) as the a.i. was separated into two suspensions, a fraction consisting of nano-sized capsules (~250 nm) and a fraction of micron sized capsules (~2200 nm) in order to investigate the influence of capsule size on toxicity to embryonic zebrafish, Danio rerio. Toxicity was evaluated 24h after exposure to equivalent amounts of a.i. by the presence and severity of pyrethroid specific tremors, 14 sublethal developmental impacts and mortality. Fish exposed to greater than 20 MUg a.i. L(-1) technical lambda-Cy or formulated product experienced curvature of the body axis, pericardial edema, craniofacial malformations, and mortality. Exposure to the unfractionated formulation, micro fraction, nano fraction and technical a.i. resulted in no significant differences in the occurrence of sublethal impacts or mortality; however, the technical a.i. exposure resulted in significantly less fish experiencing tremors and shorter tremors compared to any of the formulated product exposures. This suggests that the capsule size does not influence the toxic response of the entrapped lambda Cy, but the presence or absence of the capsules does. Testing across other encapsulated products is needed to determine if size does not have influence on toxicity regardless of encapsulation technology. PMID- 26540087 TI - Do car-mounted mobile measurements used for radio-frequency spectrum regulation have an application for exposure assessments in epidemiological studies? AB - Knowing the spatial and temporal trends in environmental exposure to radiofrequency electromagnetic fields is important in studies investigating whether there are associated health effects on humans and ecological effects on plants and animals. The main objective of this study is to assess whether the RFeye car-mounted mobile measurement system used for radio frequency spectrum monitoring in The Netherlands and the United Kingdom could be of value in assessing exposure over large areas as an alternative to measuring exposure with personal exposure meters or using complex modelling techniques. We evaluated the responses of various body-worn personal exposure meters in comparison with the mobile measurement system for spectrum monitoring. The comparison was restricted to downlink mobile communication in the GSM900 and GSM1800 frequency bands. Repeated measurements were performed in three areas in Cambridge, United Kingdom and in three areas in Amersfoort, The Netherlands. We found that exposure assessments through the car-mounted measurements are at least of similar quality to exposure modelling and better than the body worn exposimeter data due to the absence of the shielding effect. The main conclusion is that the mobile measurements provide an efficient and low cost alternative particularly in mapping large areas. PMID- 26540088 TI - Momentary affect and risky behavior correlates of prescription drug misuse among young adult dating couples: An experience sampling study. AB - Although published research based on retrospective survey designs has established prescription drug misuse as a serious health issue for individuals and society, misuse behavior has not been investigated as it occurs in daily life and important relationships. To address this gap, young adult romantic couples were recruited from the community to participate in an experience sampling study. Participants were identified through phone screen procedures as having engaged in recent prescription drug misuse behavior. Participants (n=46 couples) completed electronic diary reports throughout the day for 10days, tapping momentary affect, sexual experiences, prescription drug misuse, and alcohol and other drug use. Dyadic multilevel modeling revealed a more consistent pattern of associations between prescription drug misuse and problematic affective and behavioral outcomes for female partners than male partners. Specifically, during epochs of females' prescription drug misuse, they experienced relatively higher levels of negative affect and sexual regret. Also, females who misused prescriptions more during the study period evidenced lower levels of sexual enjoyment and engaged in more unprotected sex, alcohol use, and heavy alcohol use in daily life. Males' in the-moment prescription drug misuse was not associated with their concurrent outcomes, though males with relatively more misuse across the reporting period were more likely to engage in heavy drinking. Couples' time together emerged as a moderator of prescription drug misuse in daily life: Females who spent relatively more time with their partner across the study were less likely to engage in misuse, and proportion of time spent together moderated several of the momentary misuse-outcome linkages. This study supports the use of ecologically-valid sampling methods for characterizing young adults' prescription drug misuse in daily life and relationship contexts. PMID- 26540089 TI - Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates. AB - Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that deterministic alternatives may misjudge connectivity results by drawing conclusions from noisy and limited data. PMID- 26540090 TI - 50 MUm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis. AB - Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 MUm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 MUm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 MUm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered. PMID- 26540091 TI - Detection and Monitoring of Amyloid Fibrillation Using a Fluorescence "Switch-On" Probe. AB - Amyloid protein fibrillation is associated with a variety of neurodegenerative and other diseases, and their efficient detection and monitoring can greatly advance early diagnosis and therapy. Herein, we report a fluorescent "switch-on" probe for the reliable detection and monitoring of amyloid fibrils. The probe consists of a peptide component for binding with amyloid structure and a color component with an aggregation-induced green emission property. This probe is nonfluorescent in the presence of amyloid forming monomer protein/peptide, but fluorescence "switch-on" occurs after binding with amyloid fibrils. Compared to conventionally used thioflavin T, this probe offers a high signal-to-noise ratio, which is unaffected by the quencher ion/nanoparticle. The proposed new probe has been used for the detection and monitoring of amyloid fibrils produced by a wide variety of amyloid protein/peptides and can be extended for in vitro diagnostic applications. PMID- 26540092 TI - Exploring the Relationship of Patient and Informal Caregiver Characteristics with Heart Failure Self-Care Using the Actor-Partner Interdependence Model: Implications for Outpatient Palliative Care. AB - BACKGROUND: The convergence of prevalence, cost, symptom experience, community setting, and informal caregiving in heart failure (HF) has profound implications for outpatient palliative care. The majority of HF patients depend on informal caregiver's assistance. Dyadic (patients and caregiver) characteristics can complicate this assistance. Yet relatively little is known concerning dyadic characteristics' impact on self-care. HF self-care involves routine, daily treatment adherence and symptom monitoring (self-care maintenance), and symptom response (self-care management). OBJECTIVE: Describe the dyadic characteristics of mood and perception of the relationship in HF patients and caregivers, then explore the relationship of the characteristics with self-care. DESIGN: Prospective, cross sectional study of hospitalized HF patients in mixed dyads (spousal/adult child/relative) analyzed using Actor-Partner Interdependence Model (APIM) techniques. MEASUREMENTS: Mood was measured by the Brief Symptom Inventory and Patient Health Questionnaire, perception of the relationship by the Dyadic Adjustment Scale, and self-care by the Self-care in Heart Failure Index. RESULTS: In 40 dyads the average patient was a 71 year old male (n = 30); caregiver was a 59 years old female (n = 26). Overall self-care scores were consistently low. Patient depression scores were significantly greater than caregivers (p = .0055). Greater caregiver anxiety were associated with lower caregiver maintenance scores (p < .0001) but greater caregiver depression were associated with lower patient maintenance scores (p < .0001). While patient and caregiver's perception of the relationship was associated with their self-care, more importantly, caregiver's perception of the relationship was associated with their confidence to engage in the patient's self-care (p = .003). DISCUSSION/CONCLUSION: This study suggests that caregivers, often unacknowledged or unmeasured, impact patient's day to day HF self-care. Palliative care clinicians need to talk to dyads with a history of poor self-care about their relationship. PMID- 26540093 TI - Penicyclones A-E, Antibacterial Polyketides from the Deep-Sea-Derived Fungus Penicillium sp. F23-2. AB - Five new ambuic acid analogues, penicyclones A-E (1-5), were isolated from the extract of the deep-sea-derived fungus Penicillium sp. F23-2. The structures including the absolute configurations were established by interpretation of NMR and MS data, as well as the application of ECD, X-ray crystallography, and a chemical conversion, as well as the TDDFT-ECD calculations. Penicyclones A-E (1 5) exhibited antimicrobial activity against the Gram-positive bacterium Staphylococcus aureus with MIC values ranging from 0.3 to 1.0 MUg/mL. PMID- 26540095 TI - Development and characterization of pH responsive polymeric nanoparticles of SN 38 for colon cancer. AB - 7-Ethyl-10-hydroxycamptothecin (SN-38) is 1000 times more cytotoxic than its prodrug Irinotecan hydrochloride (CPT-11). It is not used therapeutically because of its insolubility in acceptable solvents. The objective of the present study was to prepare chitosan nanoparticles (CsENP) of SN-38 by polyelectrolyte complexation method using the Box-Behnken design. CsENPs were evaluated for mean particle size, drug loading, entrapment efficiency and characterized by TEM, XRD, DSC and FTIR. The actual values represented good agreement with predicted values. Drug release behavior in simulated colonic fluid followed Higuchi kinetics. CsENPs were stable and can be used further for treatment of colon cancer by oral route. PMID- 26540094 TI - Blocking the association of HDAC4 with MAP1S accelerates autophagy clearance of mutant Huntingtin. AB - Autophagy controls and executes the turnover of abnormally aggregated proteins. MAP1S interacts with the autophagy marker LC3 and positively regulates autophagy flux. HDAC4 associates with the aggregation-prone mutant huntingtin protein (mHTT) that causes Huntington's disease, and colocalizes with it in cytosolic inclusions. It was suggested HDAC4 interacts with MAP1S in a yeast two-hybrid screening. Here, we found that MAP1S interacts with HDAC4 via a HDAC4-binding domain (HBD). HDAC4 destabilizes MAP1S, suppresses autophagy flux and promotes the accumulation of mHTT aggregates. This occurs by an increase in the deacetylation of the acetylated MAP1S. Either suppression of HDAC4 with siRNA or overexpression of the MAP1S HBD leads to stabilization of MAP1S, activation of autophagy flux and clearance of mHTT aggregates. Therefore, specific interruption of the HDAC4-MAP1S interaction with short peptides or small molecules to enhance autophagy flux may relieve the toxicity of mHTT associated with Huntington's disease and improve symptoms of HD patients. PMID- 26540096 TI - The properties of mesoporous silica nanoparticles functionalized with different PEG-chain length via the disulfide bond linker and drug release in glutathione medium. AB - In this paper, a novel drug-loaded material (MSNs-SS-PEG) was obtained by grafting the thiol-linked methoxy polyethylene glycol (MeOPEG-SH) onto the thiol functionalized mesoporous silica nanoparticles (MSNs-SH) via the disulfide bond linker. In our designed experiment, three different chain lengths of PEG (PEG(1000), PEG(5000), and PEG(1000)-PEG(5000)) were used. The silica materials were characterized by Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption measurements, and X-ray diffraction. The morphology of the MSNs-SS-PEG was spherical with an average diameter of about 150 nm. Due to the covalent modification of hydrophilic MeOPEG, the MSNs-SS-PEG was coated by a thin polymer shell, showing stable and inerratic MCM-41 type mesoporous structure as well as high specific surface areas and large pore volumes. Moreover, the releases of doxorubicin hydrochloride (DOX) from these materials at 10 mM of glutathione were investigated. The PEG functionalization could effectively cap drugs in the mesoporous channels. The release of DOX from the MSNs-SS-PEG(n) revealed redox-responsive characteristic. The obtained results showed that the MSNs-SS-PEG might be promising drug delivery carrier materials, which could play an important role in the development of drug delivery. PMID- 26540097 TI - A Deep Cavitand Templates Lactam Formation in Water. AB - Cyclization reactions are common processes in organic chemistry and show familiar patterns of reaction rates vs ring size. While the details vary with the nature of bond being made and the number of unsaturated atoms, small rings typically form quickly despite angle strain, medium size rings form very slowly due to internal strains, and large rings form slowly (when they form at all) because fewer and less probable conformations bring the ends of the substrate together. High dilution is commonly used to slow the competing bi- and higher molecular processes. Here we apply cavitands to the formation of medium size lactams from omega-amino acids in aqueous (D2O) solution. The cavitands bind the amino acids in folded conformations that favor cyclization by bringing the ends closer together. Yields of a 12-membered lactam are improved 4.1-fold and 13-membered lactam 2.8-fold by the cavitand template. The results open possibilities for moving organic reactions into water even when the processes involve dehydration. PMID- 26540098 TI - Multiplanar Knee Laxity and Perceived Function During Activities of Daily Living and Sport. AB - CONTEXT: Greater knee-joint laxity may lead to a higher risk of knee injury, yet it is unknown whether results of self-reported outcome measures are associated with distinct knee-laxity profiles. OBJECTIVE: To identify the extent to which multiplanar knee laxity is associated with patient-reported outcomes of knee function in healthy individuals during activities of daily living and sport. DESIGN: Descriptive laboratory study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty healthy individuals (20 men, 20 women; age = 18-31 years). MAIN OUTCOME MEASURE(S): All participants were given the Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL) and Sports Activities Scale (KOS-SAS) and subsequently measured for knee laxity in the sagittal, frontal, and transverse planes. Separate backward stepwise regression analyses were performed to determine the extent to which multiplanar knee-laxity values predicted KOS-ADL and KOS-SAS scores within each sex. RESULTS: Women had higher magnitudes of anterior, posterior (POST(LAX)), varus (VAR(LAX)), valgus (VAL(LAX)), and internal-rotation laxity than men and trended toward greater external rotation (ER(LAX)) laxity. Greater POST(LAX), less VAL(LAX), and greater VAR(LAX) was associated with lower KOS-ADL scores (KOS-ADL = -4.8 [POST(LAX)], + 3.3 [VAL(LAX)] - 2.2 [VAR(LAX)] + 100.4, R2 = 0.74, P < .001) and greater POST(LAX) and less VAL(LAX) was associated with lower KOS-SAS scores (KOS-SAS = 8.2 [POST(LAX)], + 3.6 [VAL(LAX)] + 96.4, R2 = 0.67, P < .001) in women. In men, greater POST(LAX) and less ER(LAX) was associated with lower KOS-SAS scores (KOS ADL = -4.7 [POST(LAX)], + 0.9 [ER(LAX)] + 96.4, R2 = 0.49, P < .001). CONCLUSIONS: The combination of POST(LAX) with less relative VAL(LAX) (women) or less relative ER(LAX) (men) was a strong predictor of KOS scores, suggesting that a self-reported outcome measure may be beneficial as part of a preparticipation screening battery to identify those with perceived functional deficits associated with their knee laxity. PMID- 26540099 TI - Concussion-Related Protocols and Preparticipation Assessments Used for Incoming Student-Athletes in National Collegiate Athletic Association Member Institutions. AB - CONTEXT: National Collegiate Athletic Association (NCAA) legislation requires that member institutions have policies to guide the recognition and management of sport-related concussions. Identifying the nature of these policies and the mechanisms of their implementation can help identify areas of needed improvement. OBJECTIVE: To estimate the characteristics and prevalence of concussion-related protocols and preparticipation assessments used for incoming NCAA student athletes. DESIGN: Cross-sectional study. SETTING: Web-based survey. PATIENTS OR OTHER PARTICIPANTS: Head athletic trainers from all 1113 NCAA member institutions were contacted; 327 (29.4%) completed the survey. INTERVENTION(S): Participants received an e-mail link to the Web-based survey. Weekly reminders were sent during the 4-week window. MAIN OUTCOME MEASURE(S): Respondents described concussion-related protocols and preparticipation assessments (eg, concussion history, neurocognitive testing, balance testing, symptom checklists). Descriptive statistics were compared by division and football program status. RESULTS: Most universities provided concussion education to student-athletes (95.4%), had return-to-play policies (96.6%), and obtained the number of previous concussions sustained by incoming student-athletes (97.9%). Fewer had return-to learn policies (63.3%). Other concussion-history-related information (e.g., symptoms, hospitalization) was more often collected by Division I universities. Common preparticipation neurocognitive and balance tests were the Immediate Post Concussion Assessment and Cognitive Testing (ImPACT; 77.1%) and Balance Error Scoring System (46.5%). In total, 43.7% complied with recommendations for preparticipation assessments that included concussion history, neurocognitive testing, balance testing, and symptom checklists. This was due to moderate use of balance testing (56.6%); larger proportions used concussion history (99.7%), neurocognitive testing (83.2%), and symptom checklists (91.7%). More Division I universities (55.2%) complied with baseline assessment recommendations than Division II (38.2%, chi2 = 5.49, P = .02) and Division III (36.1%, chi2 = 9.11, P = .002) universities. CONCLUSIONS: National Collegiate Athletic Association member institutions implement numerous strategies to monitor student-athletes. Division II and III universities may need additional assistance to collect in depth concussion histories and conduct balance testing. Universities should continue developing or adapting (or both) return-to-learn policies. PMID- 26540100 TI - Direct Visualization of DNA Replication Dynamics in Zebrafish Cells. AB - Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ~ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells. PMID- 26540101 TI - Collagen Sequence Analysis of the Extinct Giant Ground Sloths Lestodon and Megatherium. AB - For over 200 years, fossils of bizarre extinct creatures have been described from the Americas that have ranged from giant ground sloths to the 'native' South American ungulates, groups of mammals that evolved in relative isolation on South America. Ground sloths belong to the South American xenarthrans, a group with modern although morphologically and ecologically very different representatives (anteaters, armadillos and sloths), which has been proposed to be one of the four main eutherian clades. Recently, proteomics analyses of bone collagen have recently been used to yield a molecular phylogeny for a range of mammals including the unusual 'Malagasy aardvark' shown to be most closely related to the afrotherian tenrecs, and the south American ungulates supporting their morphological association with condylarths. However, proteomics results generate partial sequence information that could impact upon the phylogenetic placement that has not been appropriately tested. For comparison, this paper examines the phylogenetic potential of proteomics-based sequencing through the analysis of collagen extracted from two extinct giant ground sloths, Lestodon and Megatherium. The ground sloths were placed as sister taxa to extant sloths, but with a closer relationship between Lestodon and the extant sloths than the basal Megatherium. These results highlight that proteomics methods could yield plausible phylogenies that share similarities with other methods, but have the potential to be more useful in fossils beyond the limits of ancient DNA survival. PMID- 26540102 TI - On the Discovery of TOR As the Target of Rapamycin. PMID- 26540103 TI - Natural Conception May Be an Acceptable Option in HIV-Serodiscordant Couples in Resource Limited Settings. AB - Many HIV serodiscordant couples have a strong desire to have their own biological children. Natural conception may be the only choice in some resource limited settings but data about natural conception is limited. Here, we reported our findings of natural conception in HIV serodiscordant couples. Between January 2008 and June 2014, we retrospectively collected data on 91 HIV serodiscordant couples presenting to Beijing Youan Hospital with childbearing desires. HIV counseling, effective ART on HIV infected partners, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in negative female partners and timed intercourse were used to maximally reduce the risk of HIV transmission. Of the 91 HIV serodiscordant couples, 43 were positive in male partners and 48 were positive in female partners. There were 196 unprotected vaginal intercourses, 100 natural conception and 97 newborns. There were no cases of HIV seroconversion in uninfected sexual partners. Natural conception may be an acceptable option in HIV serodiscordant couples in resource limited settings if HIV-positive individuals have undetectable viremia on HAART, combined with HIV counseling, PrEP, PEP and timed intercourse. PMID- 26540104 TI - Antibiotic Prescribing among Pediatric Inpatients with Potential Infections in Two Private Sector Hospitals in Central India. AB - INTRODUCTION: Infectious diseases are one of the major causes of child mortality in India. Pediatric patients are commonly prescribed antibiotics for non bacterial infections. Monitoring of local antibiotic prescribing with respect to the diagnosis is necessary to improve the prescribing practices. The aim of the study was to describe antibiotic prescribing for potential infections among patients admitted in pediatric departments in two private sector hospitals; one teaching (TH) and one non-teaching (NTH) in Central India. METHODS: Data from all patients admitted at the pediatric departments of both study hospitals was collected manually, for 3 years (2008-2011) using a customized form. Data from inpatients aged 0-18 years, diagnosed with; acute gastroenteritis (AGE), respiratory tract infections, enteric fever, viral fever or unspecified fever were focused for analysis. Antibiotic prescriptions were analysed using the WHO Anatomical Therapeutic Chemical (ATC) classification system and defined daily doses (DDDs). Adherence to the Indian Academy of Pediatrics list of essential medicines (IAP-LEM) was investigated. P-values <0.05 were considered significant. RESULTS: Oftotal6, 825 inpatients admitted at two pediatric departments, 510 patients from the TH and 2,479from the NTH were selected based on the assigned potential infectious diagnoses. Of these, 224 patients (44%) at the TH and 2,088 (84%) at the NTH were prescribed at least one antibiotic during hospital stay (odds ratio-0.69, 95%confidence interval-0.52 to 0.93; p<0.001). Patients with AGE, viral- and enteric fever were frequently prescribed antibiotics at both hospitals, yet higher proportion were prescribed antibiotics at the NTH compared to the TH. Broad-spectrum antibiotics were the most commonly prescribed antibiotic class in both hospitals, namely third generation cephalosporins, J01DD (69%) at the TH, and new fixed dose combinations of antibiotics J01R (FDCs, 42%) at the NTH. At the TH, 37% of the antibiotic prescriptions were comprised of antibiotics listed in the IAP-LEM, compared to 24% at the NTH (p<0.05). CONCLUSIONS: Broad-spectrum antibiotics were prescribed frequently in both hospitals also for the un-indicated conditions such as viral fever and enteric fever. At the NTH, new FDCs were more frequently prescribed and adherence to the IAP-LEM was substantially lower at the NTH compared to the TH. The results demonstrate need to develop diagnosis-specific prescribing guidelines to facilitate rational use of antibiotics and implement antibiotic stewardship program. PMID- 26540105 TI - How Big of an Effect Do Small Dams Have? Using Geomorphological Footprints to Quantify Spatial Impact of Low-Head Dams and Identify Patterns of Across-Dam Variation. AB - Longitudinal connectivity is a fundamental characteristic of rivers that can be disrupted by natural and anthropogenic processes. Dams are significant disruptions to streams. Over 2,000,000 low-head dams (<7.6 m high) fragment United States rivers. Despite potential adverse impacts of these ubiquitous disturbances, the spatial impacts of low-head dams on geomorphology and ecology are largely untested. Progress for research and conservation is impaired by not knowing the magnitude of low-head dam impacts. Based on the geomorphic literature, we refined a methodology that allowed us to quantify the spatial extent of low-head dam impacts (herein dam footprint), assessed variation in dam footprints across low-head dams within a river network, and identified select aspects of the context of this variation. Wetted width, depth, and substrate size distributions upstream and downstream of six low-head dams within the Upper Neosho River, Kansas, United States of America were measured. Total dam footprints averaged 7.9 km (3.0-15.3 km) or 287 wetted widths (136-437 wetted widths). Estimates included both upstream (mean: 6.7 km or 243 wetted widths) and downstream footprints (mean: 1.2 km or 44 wetted widths). Altogether the six low head dams impacted 47.3 km (about 17%) of the mainstem in the river network. Despite differences in age, size, location, and primary function, the sizes of geomorphic footprints of individual low-head dams in the Upper Neosho river network were relatively similar. The number of upstream dams and distance to upstream dams, but not dam height, affected the spatial extent of dam footprints. In summary, ubiquitous low-head dams individually and cumulatively altered lotic ecosystems. Both characteristics of individual dams and the context of neighboring dams affected low-head dam impacts within the river network. For these reasons, low-head dams require a different, more integrative, approach for research and management than the individualistic approach that has been applied to larger dams. PMID- 26540108 TI - A Multi-Level Bayesian Analysis of Racial Bias in Police Shootings at the County Level in the United States, 2011-2014. AB - A geographically-resolved, multi-level Bayesian model is used to analyze the data presented in the U.S. Police-Shooting Database (USPSD) in order to investigate the extent of racial bias in the shooting of American civilians by police officers in recent years. In contrast to previous work that relied on the FBI's Supplemental Homicide Reports that were constructed from self-reported cases of police-involved homicide, this data set is less likely to be biased by police reporting practices. County-specific relative risk outcomes of being shot by police are estimated as a function of the interaction of: 1) whether suspects/civilians were armed or unarmed, and 2) the race/ethnicity of the suspects/civilians. The results provide evidence of a significant bias in the killing of unarmed black Americans relative to unarmed white Americans, in that the probability of being {black, unarmed, and shot by police} is about 3.49 times the probability of being {white, unarmed, and shot by police} on average. Furthermore, the results of multi-level modeling show that there exists significant heterogeneity across counties in the extent of racial bias in police shootings, with some counties showing relative risk ratios of 20 to 1 or more. Finally, analysis of police shooting data as a function of county-level predictors suggests that racial bias in police shootings is most likely to emerge in police departments in larger metropolitan counties with low median incomes and a sizable portion of black residents, especially when there is high financial inequality in that county. There is no relationship between county-level racial bias in police shootings and crime rates (even race-specific crime rates), meaning that the racial bias observed in police shootings in this data set is not explainable as a response to local-level crime rates. PMID- 26540106 TI - Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling. AB - Mutations in genes encoding cilia proteins cause human ciliopathies, diverse disorders affecting many tissues. Individual genes can be linked to ciliopathies with dramatically different phenotypes, suggesting that genetic modifiers may participate in their pathogenesis. The ciliary transition zone contains two protein complexes affected in the ciliopathies Meckel syndrome (MKS) and nephronophthisis (NPHP). The BBSome is a third protein complex, affected in the ciliopathy Bardet-Biedl syndrome (BBS). We tested whether mutations in MKS, NPHP and BBS complex genes modify the phenotypic consequences of one another in both C. elegans and mice. To this end, we identified TCTN-1, the C. elegans ortholog of vertebrate MKS complex components called Tectonics, as an evolutionarily conserved transition zone protein. Neither disruption of TCTN-1 alone or together with MKS complex components abrogated ciliary structure in C. elegans. In contrast, disruption of TCTN-1 together with either of two NPHP complex components, NPHP-1 or NPHP-4, compromised ciliary structure. Similarly, disruption of an NPHP complex component and the BBS complex component BBS-5 individually did not compromise ciliary structure, but together did. As in nematodes, disrupting two components of the mouse MKS complex did not cause additive phenotypes compared to single mutants. However, disrupting both Tctn1 and either Nphp1 or Nphp4 exacerbated defects in ciliogenesis and cilia associated developmental signaling, as did disrupting both Tctn1 and the BBSome component Bbs1. Thus, we demonstrate that ciliary complexes act in parallel to support ciliary function and suggest that human ciliopathy phenotypes are altered by genetic interactions between different ciliary biochemical complexes. PMID- 26540107 TI - Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry. AB - BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in 'real-world' AF patients are limited, especially from large prospective Asian cohorts. METHODS: The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for 'death, stroke, and systemic embolism (SE)' during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. RESULTS: The mean age was 73.1 +/- 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24-2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25-2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25-2.30), heart failure (HR: 1.59, 95% CI: 1.17-2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16-2.02), and anemia (HR: 2.41, 95% CI: 1.78-3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. CONCLUSIONS: Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID- 26540109 TI - Biophotonics and the life sciences. PMID- 26540110 TI - Retraction of: J Clin Las Med Surg 2004;22(2):87-89 DOI: 10.1089/104454704774076127. PMID- 26540111 TI - Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia. AB - OBJECTIVES: Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA. METHODS: Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21-80) years. The control group comprised 34 age- and sex- matched volunteers. RESULTS: Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30+/-0.93 vs 10.14+/-1.07 10-9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8+/-3.6 vs 47.4+/-2.9 s), thicker fibrin fibers (maximum absorbance, DeltaAbs, 0.87+/-0.09 vs 0.72+/-0.07), higher maximum levels of D dimer released from clots (DDmax 4.10+/-0.46 vs 3.54+/-0.35 mg/L), and prolonged clot lysis time (t50%; 9.50+/-1.45 vs 7.56+/-0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%. CONCLUSION: This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease. PMID- 26540112 TI - Hoechst 33342 Is a Hidden "Janus" amongst Substrates for the Multidrug Efflux Pump LmrP. AB - Multidrug transporters mediate the active extrusion of antibiotics and toxic ions from the cell. This reaction is thought to be based on a switch of the transporter between two conformational states, one in which the interior substrate binding cavity is available for substrate binding at the inside of the cell, and another in which the cavity is exposed to the outside of the cell to enable substrate release. Consistent with this model, cysteine cross-linking studies with the Major Facilitator Superfamily drug/proton antiporter LmrP from Lactococcus lactis demonstrated binding of transported benzalkonium to LmrP in its inward-facing state. The fluorescent dye Hoechst 33342 is a substrate for many multidrug transporters and is extruded by efflux pumps in microbial and mammalian cells. Surprisingly, and in contrast to other multidrug transporters, LmrP was found to actively accumulate, rather than extrude, Hoechst 33342 in lactococcal cells. Consistent with this observation, LmrP expression was associated with cellular sensitivity, rather than resistance to Hoechst 33342. Thus, we discovered a hidden "Janus" amongst LmrP substrates that is translocated in reverse direction across the membrane by binding to outward-facing LmrP followed by release from inward-facing LmrP. These findings are in agreement with distance measurements by electron paramagnetic resonance in which Hoechst 33342 binding was found to stabilize LmrP in its outward-facing conformation. Our data have important implications for the use of multidrug exporters in selective targeting of "Hoechst 33342-like" drugs to cells and tissues in which these transporters are expressed. PMID- 26540113 TI - Right Temporal Lobe Atrophy: A Case That Initially Presented as Excessive Piety. AB - OBJECTIVE: Variants of frontotemporal lobar degeneration (FTLD) are associated with distinct clinical, pathological, and neuroanatomical profiles. Lines of emerging research indicate a rare variant with focal atrophy of the right temporal lobe (RTLA). The objective was to present case data and discussion of an individual with RTLA in order to assist with conceptualization of this variant. METHOD: A 60-year-old, right-handed, college-educated Protestant minister with RTLA was evaluated. This patient presented with several hallmark behavioral and psychiatric features with personality changes, including hyper-religiosity, depression, and social disinhibition. Given the profession of the patient, the observed personality alterations (e.g., religiosity and pietism) were initially excused, which delayed diagnosis. RESULTS: In addition to cognitive deficits, an examination of affect processing within visual and auditory channels revealed severe impairment in emotion recognition with features of prosopagnosia. These impairments were in general more severe than the cognitive impairment observed on traditional neuropsychological measures. CONCLUSIONS: This case provides support for an FTLD right temporal lobe variant. This case also illustrates the importance of neuropsychological evaluation of affect processing in the differential diagnosis and treatment planning for FTLD and its subtypes. PMID- 26540114 TI - Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging. AB - BACKGROUND AND OBJECTIVE: The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure. METHODS: C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo. RESULTS: The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues. CONCLUSIONS: [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors. PMID- 26540115 TI - Multidrug-Resistant Salmonella Heidelberg Associated with Mechanically Separated Chicken at a Correctional Facility. AB - We describe multidrug-resistant (MDR) Salmonella Heidelberg infections associated with mechanically separated chicken (MSC) served at a county correctional facility. Twenty-three inmates met the case definition. All reported diarrhea, 19 (83%) reported fever, 16 (70%) reported vomiting, 4 (17%) had fever >=103 degrees F, and 3 (13%) were hospitalized. A case-control study found no single food item significantly associated with illness. Salmonella Heidelberg with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from nine stool specimens; two isolates displayed resistance to a total of five drug classes, including the third-generation cephalosporin, ceftriaxone. MDR Salmonella Heidelberg might have contributed to the severity of illness. Salmonella Heidelberg indistinguishable from the outbreak subtype was isolated from unopened MSC. The environmental health assessment identified cross contamination through poor food-handling practices as a possible contributing factor. Proper hand-washing techniques and safe food-handling practices were reviewed with the kitchen supervisor. PMID- 26540116 TI - The Association of Vitamin D Receptor Polymorphisms with Multiple Sclerosis in a Case-Control Study from Kuwait. AB - Vitamin D deficiency is associated with several diseases including multiple sclerosis (MS). Several factors influence vitamin D levels and its optimal multi function maintenance. Our objective was to assess quantifiable variables influencing vitamin D level and metabolism in MS patients from Kuwait. In a case control study involving 50 MS patients, and 50 healthy control individuals for which plasma vitamin D levels, supplement use, vitamin D receptor (VDR) variants, and skin pigmentation indices were ascertained; we found overall vitamin D levels to be deficient in both groups, and supplement use to be common practice. VDR variants TaqI and BsmI associated with MS risk, and ApaI associated with low disease progression. VDR variant FokI associated with higher vitamin D levels in both groups. We conclude that several quantifiable variables related to vitamin D associate with MS suggesting a possible clinical immuno-modulatory application of vitamin D for MS patients in Kuwait. PMID- 26540117 TI - Perfluorinated carboxylic and sulphonic acids in surface water media from the regions of Tibetan Plateau: Indirect evidence on photochemical degradation? AB - Perfluorinated surfactants and repellents are synthetic substances that have found numerous industrial and customer applications. Due to their persistence, at least two groups of these substances-perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonic acids (PFSAs)-are diffused widely in the environment. It is hypothesized that the Tibetan Plateau, is one of few unique places on the Earth, due to its topography, specifically the vast space and high elevation above sea level, geographic location, climate, high solar radiation, lack of industry, little urbanization and general lack of significant direct sources of pollution. There it is believed possible to gain an insight into atmospheric fate (possible photochemical degradation of higher molecular mass and formation of lower molecular mass PFCAs and PFSAs) of PFASs under un-disturbed environmental conditions. Ultratrace analytical method for PFCAs and PFSAs and use of transportation and field blanks, laboratory blanks and isotopically labelled surrogates for recovery control has allowed the determination of nine perfluorinated carboxylic acids and six perfluorinated sulfonic acids at ultra trace levels in water based samples from the alpine dimension regions of the Tibetan Plateau, the eastern slope of Minya Konka peak at the eastern edge of the Tibetan Plateau, and also from the city of Chengdu from the lowland of the Sichuan Province in China. The specific compositional pattern of PFCAs and PFSAs and low levels of pollution with those compounds were observed in the central region of the Tibetan Plateau and in the region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau. The fingerprint of the compositional pattern of PFCAs and PFSAs in water samples in the central region of the Tibetan Plateau and in the alpine region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau may be explained by the result of photochemical degradation with dealkylation of longer chain compounds and formation of shorter chain compounds, which are more resistant to photochemical degradation. PMID- 26540118 TI - Timosaponin B-II inhibits lipopolysaccharide-induced acute lung toxicity via TLR/NF-kappaB pathway. AB - Timosaponin B-II (TB), a main bioactive compound in Anemarrhena asphodeloides Bunge, has various kinds of pharmacological activities, the present study aimed to investigate the protective role of TB on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS, and TB (20 and 60 mg/kg) was given orally 1 h prior to LPS administration. After 6 h, bronchoalveolar lavagefluid (BALF) and lung tissue were collected. TB decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity. In addition, TB inhibited inflammatory cells and cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in BALF. Furthermore, we demonstrated that TB inhibited the Toll-like receptor-2 (TLR2), Toll-like receptor-4 (TLR4), myeloid differentiation primary response gene-88 (MyD88), nuclear factor-kappaB (NF-kappaB) p65 in LPS-induced ALI. These results showed that administration of TB prior to LPS improves ALI, possibly mediating ALI through suppressing TLR/NF-kappaB pathway activation. PMID- 26540119 TI - Prostaglandin-Associated Enophthalmos: An Observer-Masked Radiological Study of Patients Treated with Prostaglandin Drops to One Eye Only. PMID- 26540120 TI - Estimating the Total Pathogenic Allele Frequency of Autosomal Recessive Disorders in Case of Consanguinity. AB - OBJECTIVE: Estimating the total allele frequency of all pathogenic alleles of an autosomal recessive disease is not possible if only mutational data of a sample of affected individuals are available. However, if the affected individuals come from a population where consanguinity is not uncommon, this total allele frequency can be estimated by additionally using the positive individual inbreeding coefficients or an estimate of the population inbreeding coefficient. In this paper, we propose two estimators. METHODS/RESULTS: We propose to estimate the total allele frequency by a conditional maximum likelihood estimator if a part of the affected individuals in the sample comes from consanguineous marriages with known inbreeding coefficients. A simulation study shows that this estimator is unbiased and robust. We propose a second estimator which is based on an estimate of the population inbreeding coefficient. The method is applied to mutational data and individual inbreeding coefficients of Tunisian patients with congenital adrenal hyperplasia. CONCLUSION: Additionally using individual inbreeding coefficients or an estimate of the population inbreeding coefficient makes it possible to estimate the total allele frequency. Since consanguinity is commonly practiced in many parts of the world, the estimators proposed in the paper are of practical importance. PMID- 26540121 TI - From Basic Biology to Engineering and Clinical Translation of Stem Cells: Meeting Report on the 8th International Meeting of the Stem Cell Network North Rhine Westphalia. PMID- 26540122 TI - The complete mitochondrial genome of Acrossocheilus beijiangensis (Cyprinidae, Barbinae). AB - Acrossocheilus beijiangensis is a species of freshwater fish in the family Cyprinidae. In this study, the complete mitochondrial genome of A. beijiangensis has been determined using polymerase chain reaction technique. The genome is 16 600 bp in length, it includes 22 tRNA genes, 13 protein-coding genes, two rRNA genes, a D-loop control region, and another non-coding region called replication origin of Light strand (OL). The order of mitochondrial genes was found to be analogous to other vertebrates. The overall base composition of A. beijiangensis, mitochondrial DNA, was calculated and determined to consist of 30.6% A, 24.9% T, 28.1% C, and 16.3% G. Additionally it was found that most of the mitochondrial genes are encoded on the heavy strand except the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes. The availability of A. beijangesis mitogenome will provide basic data for the systematic categorization of Acrossocheilus sp., as well as the phylogenetic analysis of Cyprinid fishes. PMID- 26540124 TI - Complex strength performance in patients with haemophilia A. Method development and testing. AB - The aim of this study was to develop a complex strength measurement method and to apply this new method for the first time in patients with haemophilia (PwH). 20 PwH with severe haemophilia A and 20 controls were included into the study. All subjects completed ten measurements of maximum isometric strength. Furthermore, the 20 control subjects completed re-test-measurements to evaluate the method. As a result, the method showed a high reliability (ICC 0.764 to 0.934). Between the two groups significant reductions in PwH between -(19-35%) were detected, regarding the relative force of the M. triceps brachii (-19%; p = 0.008), M. biceps brachii (-19%; p = 0.031), M. latissimus dorsi (-17%; p = 0.019), M. biceps femoris right (-20%; p = 0.036) and M. quadriceps femoris (right: -29%; p = 0.004; left: -35%; p = 0.002). No differences were found for M. rectus abdominis and in the hand strength. Thus, there is no general deficit in the muscle strength in PwH. The most obvious deficits exist in the upper and lower extremities and in the back muscles. CONCLUSION: PwH should carry out complex muscle strength training and integrate it early into a comprehensive treatment concept. PMID- 26540125 TI - Congenital macrothrombocytopenia associated with a combination of functional polymorphisms in the TUBB1 gene. AB - Congenital thrombocytopenia in childhood and adolescence requires an extensive diagnostic workup to find the underlying reason. We report on a 13-year-old female patient who was incidentally found to have moderate thrombocytopenia which was also diagnosed in her father and brother. Within the microscopic evaluation of a peripheral blood smear macrothrombocytes were found. Immunofluorescence microscopy of the patient's platelets detected the lack of beta1-tubulin. Analysis of the TUBB1 gene revealed three known missense variants in heterozygous state which in combination might explain the beta1-tubulin defect. PMID- 26540126 TI - Novel point mutation in fibrinogen (Innsbruck; BbetaArg44Gly). Phenotypic differences compared to another mutation (fibrinogen Nijmegen) at the same position. AB - This is a report of a novel fibrinogen point mutation (fibrinogen Innsbruck), a C/G point mutation at position 220 of exon two of the fibrinogen Bbeta-chain leading to BbetaArg44Gly. The heterozygous mutation was found in a 16-year-old adolescent, hospitalized for the management of juvenile depression, who suffered from multiple epistaxis episodes during his stay at the university hospital in Innsbruck, Austria. Fibrinogen (based on the Clauss method) and fibrinogen antigen levels were highly discrepant (86 vs. 223 mg/dl) with thrombin time and reptilase time being in the respective upper reference ranges. Densitometric analysis of electrophoretic band pattern showed a reduction of alpha-polymers, indicating an impaired fibrin polymerization. This is in agreement with structural analysis, which showed a disturbance of the flexibility and structure of the region surrounding the fibrinoeptide B cleavage site. Fibrinogen Nijmegen, a mutation at the same position, is causative for thrombosis, whereas fibrinogen Innsbruck appears to lead to a bleeding tendency, illustrating that even mutations at the same position can cause contrary symptoms. PMID- 26540123 TI - SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases. AB - S-Adenosyl-L-methionine (SAM) is a sulfonium molecule with a structural hybrid of methionine and adenosine. As the second largest cofactor in the human body, its major function is to serve as methyl donor for SAM-dependent methyltransferases (MTases). The resultant transmethylation of biomolecules constitutes a significant biochemical mechanism in epigenetic regulation, cellular signaling, and metabolite degradation. Recently, numerous SAM analogs have been developed as synthetic cofactors to transfer the activated groups on MTase substrates for downstream ligation and identification. Meanwhile, new compounds built upon or derived from the SAM scaffold have been designed and tested as selective inhibitors for important MTase targets. Here, we summarized the recent development and application of SAM analogs as chemical biology tools for MTases. PMID- 26540127 TI - A novel fibrinogen gamma chain frameshift deletion (c.637delT) in a patient with hypodysfibrinogenemia associated with thrombosis. AB - Inherited fibrinogen (FG) disorders are rare and result in quantitative or/and qualitative FG deficiency. While the majority of patients with clinically relevant FG deficiencies demonstrate a bleeding phenotype, a subset of patients are at increased risk of thrombosis. PATIENTS AND METHODS: We report a 54-years old man presenting with a thrombophilic phenotype characterized by two episodes of unprovoked venous thrombosis and a deep vein thrombosis several weeks after myocardial infarction. Recently, he developed A. carotis communis thrombosis and died. Coagulation tests were done using standard procedures. FG genes were screened using direct sequencing. Effect on fibrin clot structure was analyzed by scanning electron microscopy (SEM) and FG chain polymerization was analysed using SDS-PAGE. RESULTS: While thrombophilia testing was negative, we found a decreased concentration of clottable FG (126-148 mg/dl) compared to FG antigen (182-194 mg/dl of normal). The thrombin time was slightly prolonged, while aPTT and reptilase time were within the normal range. A novel deletion in FGG gene (c.637delT) resulting in a frameshift and the premature termination of the gamma chain at amino acid position p.228 was identified. SDS-PAGE showed a time-shift in gamma-gamma and alpha-alpha cross linking. SEM showed no statistically significant differences between the patient's and a healthy control's fibrin clot structure. CONCLUSIONS: In addition to the reduction of FG concentration expected by the nature of the mutation also a functional defect (hypodysfibrinogenemia) was found. Moreover this mutation seems to increase the risk of thrombosis warranting long term anticoagulation possibly in a combination with antiplatelet drugs. PMID- 26540128 TI - Neoplasm-induced bleeding in inherited, heterozygous FXIII-A deficiency. AB - Inherited mild factor XIII deficiency belongs to one of the most underdiagnosed bleeding disorders so far. This is, because most patients do not develop bleeding complications in daily life. Patient, methods: A man (age: 64 years) without a history of bleeding presented with painful swelling of neck, weight loss, anemia and episodic bleeding from the right tonsil necessitating tonsillectomy. Histologic and immunohistochemical evaluation revealed cytokeratin-positive epitheloid angiosarcoma. Blood coagulation status showed significantly elevated D dimer and decreased FXIII levels (FXIII-activity 35%, FXIIIA-Ag 16-26%). Plasma mixing studies excluded neutralizing antibodies against FXIII. RESULTS: A novel heterozygous F13A1 gene nonsense mutation (p.Glu103Ter, c.307G>T) was found confirming heterozygous FXIII-A deficiency. The same mutation was detected in two further asymptomatic relatives. For further clinical management the patient was transfused with FXIII-concentrate and showed an adequate increase of FXIII ruling out FXIII deficiency to be induced by increased turnover. Despite this haemostatic management and antifibrinolytic treatment the patient had to undergo several revisions due to delayed, Hb relevant bleeding after cervical lymph nodes extirpation and resection of tonsil. Two chemotherapy cycles with paclitaxel and palliative radiotherapy of the neck area were performed, but the patient died unfortunately two months after diagnosis. CONCLUSIONS: It is a unique case showing the combination of a highly aggressive angiosarcoma and presence of inherited FXIII deficiency. It is also a rare example demonstrating the benefit of FXIII genotyping besides the expected acquired FXIII deficiency possibly due to neoplasm induced increased consumption by elevated crosslinking of fibrin fibers. PMID- 26540129 TI - Large deletions play a minor but essential role in congenital coagulation factor VII and X deficiencies. AB - Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11 recurrent in the F10 gene including one homozygous 4.35 kb deletion within F7 (c.64+430_131 6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation. CONCLUSIONS: Large deletions play a minor but essential role in the mutational spectrum of the F7 and F10 genes. Copy number analyses (e. g. MLPA) should be considered if sequencing cannot clarify the underlying reason of an observed coagulopathy. Of note, in cases of combined FVII/FX deficiency, a deletion of the two contiguous genes might be part of a larger chromosomal rearrangement. PMID- 26540130 TI - [Bleedings under NOAC (non Vitamin-K dependent oral anticoagulants). Evidence and practical management]. AB - The doses of these drugs are barely tested and the potential clinical thromboembolic risk must be taken into account. Despite the widespread use of NOAC (non vitamin-K dependent oral anticoagulants) and recommendations of regulatory agencies and first consensus meeting on handling the bleeding situation under NOAC, especially in hospitals without a large hemostatic focus, uncertainty still exists. In case of mild bleeding from a clinical perspective, the medical care of these patients and the delay of the next dose or discontinuation is advised. A special laboratory analysis is indicated i.e. in case of known higher grade liver and kidney failure, which can cause a prolonged elimination of NOAC. The administration of factor concentrates is not indicated in this situation. In case of moderate to severe bleeding, the primary measures focus on the stabilization of the heart and circulatory function and parallel on the treatment depending on the localization of the bleeding source. According to experience, mostly gastrointestinal bleeding occurs under the NOAC, which should be supplied endoscopically. In life-threatening bleeding in addition to the measures of hemodynamic stabilization usually a special haemostasis management is required, which should be mainly clinically oriented. After the assessment of bleeding predictor, the time of the last dose and the dose of NOAC should be learned, but other causes of bleeding, including Fibrinolysis, should be excluded or treated. Subsequently, routinely promptly rivaroxaban and/or apixaban sensitive thromboplastin time (Quick's value) and a thrombin time (thrombin-poor calibrator) for qualitative assessment can be carried out because only very few hospitals have specific tests (anti-Xa measurements, bovine thrombin), which could be promptly done. If there is a significant deviation from the normal range or to present preliminary value of particular patient, an effect of NOAC most likely exists. In life-threatening bleeding the use of factor concentrates (procoagulants) is indicated. The first-line therapy should be PPSB. Only in exceptional cases, especially when dabigatran is taken, the use of aPPSB (FEIBA(r)) for prompt haemostasis can be considered. The haemostasis should be always clinically estimated and not according to coagulation tests. The use of rFVIIa (Novo Seven(r)) shows different results in the bleeding therapy (reversal) under Dabigatran. The doses of these drugs are barely tested and the potential clinical thromboembolic risk must be taken into account. CONCLUSION: The current concepts of the newly developed antidotes are not clinically validated. First prospective, clinical registries have been started. PMID- 26540131 TI - Neuropathic pain in patients with haemophilia, that is the question. AB - Chronic pain caused by recurrent joint bleedings affects a large number of patients with haemophilia (PwH). The basis of this pain, nociceptive or neuropathic, has not been investigated so far. In other pain-related chronic disorders such as osteoarthritis or rheumatoid arthritis, initial studies showed nociceptive but also neuropathic pain features. 137 PwH and 33 controls (C) completed the painDETECT-questionnaire (pDq), which identifies neuropathic components in a person's pain profile. Based on the pDq results, a neuropathic pain component is classified as positive, negative or unclear. A positive neuropathic pain component was found in nine PwH, but not in C. In 20 PwH an unclear pDq result was observed. In comparison to C the allocation of pDq results is statistically significant (p<=0.001). Despite various pDq results in PwH and C a similar appraisal pain quality, but on a different level, was determined. Summarising the results, there is a potential risk to misunderstand underlying pain mechanisms in PwH. In chronic pain conditions based on haemophilic arthopathy, a differential diagnosis seems to be unalterable for comprehensive and individualised pain management in PwH. PMID- 26540132 TI - Gelation by supramolecular dimerization of mono(urea)s. AB - Mono-ureido salicylic acid derivatives form hydrogen bonded dimers that mimic the gelation behaviour of covalently linked bis(urea)s. The 5-ureido salicylic acid isomers are much more effective gelators because of the lowered conjugation and less planar geometry, resulting in stronger urea...urea alpha-tape hydrogen bonding interactions. PMID- 26540133 TI - Spectroscopic Analyses on Reaction Intermediates Formed during Chlorination of Alkanes with NaOCl Catalyzed by a Nickel Complex. AB - The spectroscopic, electrochemical, and crystallographic characterization of [((Me,H)PyTACN)Ni(II)(CH3CN)2](OTf)2 (1) ((Me,H)PyTACN = 1-(2-pyridylmethyl)-4,7 dimethyl-1,4,7-triazacyclononane, OTf = CF3SO3) is described together with its reactivity with NaOCl. 1 catalyzes the chlorination of alkanes with NaOCl, producing only a trace amount of oxygenated byproducts. The reaction was monitored spectroscopically and by high resolution electrospray-mass spectrometry (ESI-MS) with the aim to elucidate mechanistic aspects. NaOCl reacts with 1 in acetonitrile to form the transient species [(L)Ni(II)-OCl(S)](+) (A) (L = (Me,H)PyTACN, S = solvent), which was identified by ESI-MS. UV/vis absorption, electron paramagnetic resonance, and resonance Raman spectroscopy indicate that intermediate A decays to the complex [(L)Ni(III)-OH(S)](2+) (B) presumably through homolytic cleavage of the O-Cl bond, which liberates a Cl(*) atom. Hydrolysis of acetonitrile to acetic acid under the applied conditions results in the formation of [(L)Ni(III)-OOCCH3(S)](2+) (C), which undergoes subsequent reduction to [(L)Ni(II)-OOCCH3(S)](2+) (D), presumably via reaction with OCl(-) or ClO2(-). Subsequent addition of NaOCl to [(L)Ni(II)-OOCCH3(S)](+) (D) regenerates [(L)Ni(III)-OH(S)](2+) (B) to a much greater extent and at a faster rate. Addition of acids such as acetic and triflic acid enhances the rate and extent of formation of [(L)Ni(III)-OH(S)](2+) (B) from 1, suggesting that O-Cl homolytic cleavage is accelerated by protonation. Overall, these reactions generate Cl(*) atoms and ClO2 in a catalytic cycle where the nickel center alternates between Ni(II) and Ni(III). Chlorine atoms in turn react with the C-H bonds of alkanes, forming alkyl radicals that are trapped by Cl(*) to form alkyl chlorides. PMID- 26540134 TI - Plasma cholesterol is related to menstrual status in adolescent girls with eating disorders and weight loss. AB - AIM: This study examined the relationship between plasma cholesterol and circulating triiodothyronine and oestradiol in 561 adolescent girls aged 11-17 with eating disorders. METHODS: Plasma total cholesterol, high-density lipoprotein cholesterol, serum triodothyronine and oestradiol were measured at assessment, and historical weight data were obtained from growth charts provided by the school health services. Cholesterol levels were related to weight change, menstrual status and serum hormones. RESULTS: Plasma total cholesterol levels of >5.0 mmol/L were found in 38% of the 77 girls who were premenarcheal, 32% of the 199 with secondary amenorrhoea and 17% of those who were still menstruating. These cholesterol levels were inversely related to serum oestradiol and triiodothyronine concentrations, but not weight change, in amenorrhoic girls and were positively related to body mass index and inversely related to weight loss and serum triiodothyronine in girls who were still menstruating. CONCLUSION: Increased plasma total cholesterol was related to amenorrhoea in adolescent girls with eating disorders and weight loss. Oestrogens appeared to mediate the effect of starvation on cholesterol, most effectively in premenarcheal girls. Re establishing menstruation is an important goal in the treatment of eating disorders, to avoid dyslipidaemia and the risk of future cardiovascular disease. PMID- 26540135 TI - Gate Controlled Photocurrent Generation Mechanisms in High-Gain In2Se3 Phototransistors. AB - Photocurrent in photodetectors incorporating van der Waals materials is typically produced by a combination of photocurrent generation mechanisms that occur simultaneously during operation. Because of this, response times in these devices often yield to slower, high gain processes, which cannot be turned off. Here we report on photodetectors incorporating the layered material In2Se3, which allow complete modulation of a high gain, photogating mechanism in the ON state in favor of fast photoconduction in the OFF state. While photoconduction is largely gate independent, photocurrent from the photogating effect is strongly modulated through application of a back gate voltage. By varying the back gate, we demonstrate control over the dominant mechanism responsible for photocurrent generation. Furthermore, because of the strong photogating effect, these direct band gap, multilayer phototransistors produce ultrahigh gains of (9.8 +/- 2.5) * 10(4) A/W and inferred detectivities of (3.3 +/- 0.8) * 10(13) Jones, putting In2Se3 among the most sensitive 2D materials for photodetection studied to date. PMID- 26540137 TI - Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task. AB - Motor imagery (MI) training and anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex can independently improve hand motor function. The main objective of this double-blind, sham-controlled study was to examine whether anodal tDCS over the primary motor cortex could enhance the effects of MI training on the learning of a finger tapping sequence. Thirty-six right-handed young human adults were assigned to one of three groups: (i) who performed MI training combined with anodal tDCS applied over the primary motor cortex; (ii) who performed MI training combined with sham tDCS; and (iii) who received tDCS while reading a book. The MI training consisted of mentally rehearsing an eight-item complex finger sequence for 13 min. Before (Pre-test), immediately after (Post-test 1), and at 90 min after (Post-test 2) MI training, the participants physically repeated the sequence as fast and as accurately as possible. An anova showed that the number of sequences correctly performed significantly increased between Pre-test and Post-test 1 and remained stable at Post-test 2 in the three groups (P < 0.001). Furthermore, the percentage increase in performance between Pre-test and Post-test 1 and Post-test 2 was significantly greater in the group that performed MI training combined with anodal tDCS compared with the other two groups (P < 0.05). As a potential physiological explanation, the synaptic strength within the primary motor cortex could have been reinforced by the association of MI training and tDCS compared with MI training alone and tDCS alone. PMID- 26540138 TI - Large-scale phenotyping links adult hippocampal neurogenesis to the reaction to novelty. AB - The discovery of adult-born neurons in the hippocampus has triggered a wide range of studies that link the new neurons to various behavioral functions. However, the role of new neurons in behavior is still equivocal. Conflicting results may be due to the difficulty in manipulating neurogenesis without off-target effects as well as the statistical approach used, which fail to account for neurogenesis independent effects of experimental manipulations on behavior. In this study, we apply a more comprehensive statistical and conceptual approach. Instead of between-group analyses, we consider the within-group relationships between neurogenesis and behavior (ANCOVA and mediation analysis) in a large-scale experiment, in which distinct age- (3 and 5 months) and strain- (DBA and C57) related differences in basal levels of neurogenesis in mice are compared with a large number (~1,500) of behavioral read outs. The analysis failed to detect any association between anxiety and motor impulsivity with neurogenesis. However, within-group adult hippocampal neurogenesis is associated with the reaction to novelty. Specifically, more neurogenesis is associated with a longer latency to explore and a lower frequency of exploratory actions, overall indicative of a phenotype where animals with more neurogenesis were slower to explore a novel environment. This effect is observed in 5-months-old, but not in 3-months-old mice of both strains. An association between the reaction to novelty and adult neurogenesis can have a major impact on results from previous studies using classical behavioral experiments, in which animals are tested in a--for the animal--novel experimental set-up. The neurogenesis-novelty association found here is also a necessary link in the relation that has been suggested to exist between neurogenesis and psychiatric disorders marked by a failure to cope with novelty. PMID- 26540136 TI - Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. AB - RATIONALE: Restoration of vitamin D sufficiency may reduce asthma exacerbations, events that are often associated with respiratory tract infections and cold symptoms. OBJECTIVES: To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency. METHODS: Colds were assessed in the AsthmaNet VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness) trial, in which 408 adult patients were randomized to receive placebo or cholecalciferol (100,000 IU load plus 4,000 IU/d) for 28 weeks as add-on therapy. The primary outcome was cold symptom severity, which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey. MEASUREMENTS AND MAIN RESULTS: A total of 203 participants experienced at least one cold. Despite achieving 25 hydroxyvitamin D levels of 41.9 ng/ml (95% confidence interval [CI], 40.1-43.7 ng/ml) by 12 weeks, vitamin D supplementation had no effect on the primary outcome: the average peak WURSS-21 scores (62.0 [95% CI, 55.1-68.9; placebo] and 58.7 [95% CI, 52.4-65.0; vitamin D]; P = 0.39). The rate of colds did not differ between groups (rate ratio [RR], 1.2; 95% CI, 0.9-1.5); however, among African Americans, those receiving vitamin D versus placebo had an increased rate of colds (RR, 1.7; 95% CI, 1.1-2.7; P = 0.02). This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency, regardless of treatment assignment (RR, 1.4; 95% CI, 1.1-1.7; P = 0.009). CONCLUSIONS: Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency. PMID- 26540139 TI - Supramolecular Construction of Multifluorescent Gels: Interfacial Assembly of Discrete Fluorescent Gels through Multiple Hydrogen Bonding. AB - Multifluorescent supramolecular gels with complex structures are constructed from discrete fluorescent gels, which serve as the building blocks, through hydrogen bonding interactions at interfaces. The multifluorescent gel can realize rapid healing within only ~100 s. PMID- 26540140 TI - Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part I: Synthesis, characterization, and myoblast proliferation and differentiation. AB - Tissue-engineered cardiac patch aims at regenerating an infarcted heart by improving cardiac function and providing mechanical support to the diseased myocardium. In order to take advantages of electroactivity, a new synthetic method was developed for the introduction of an electroactive oligoaniline into the backbone of prepared patches. For this purpose, a series of electroactive polyurethane/siloxane films containing aniline tetramer (AT) was prepared through sol-gel reaction of trimethoxysilane functional intermediate polyurethane prepolymers made from castor oil and poly(ethylene glycol). Physicochemical, mechanical, and electrical conductivity of samples were evaluated and the recorded results were correlated to their structural characteristics. The optimized films were proved to be biodegradable and have tensile properties suitable for cardiac patch application. The embedded AT moieties in the backbone of the prepared samples preserved their electroactivity with the electrical conductivity in the range of 10-4 S/cm. The prepared films were compatible with proliferation of C2C12 and had potential for enhancing myotube formation even without external electrical stimulation. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 775-787, 2016. PMID- 26540142 TI - 2015 ACR/ARHP Annual Meeting Abstract Supplement. AB - For a searchable version of these abstracts, please visit www.acrabstracts.org. Please Note: It may take several minutes for this file to download. PMID- 26540141 TI - The role of motor affordances in immediate and long-term retention of objects. AB - In line with the embodied cognition perspective stating that cognitive processing results from the activation of the sensorimotor systems involved in perception and action (e.g., Glenberg, 1997), recent studies provided evidence that motor affordances played a role in serial memory for objects (e.g., see Downing-Doucet & Guerard, 2014). In the present study, we extended this line of research by investigating whether objects' motor affordances played a role in item memory, in immediate and long-term retention. Participants had to retain pairs of objects that were positioned in a way that was congruent for action or not. The results showed that motor suppression disrupted the retention of congruent pairs, but not that of incongruent pairs when short lists of six objects had to be retained over a short period of time (Experiment 1). However, when participants had to retain lists of 60 pairs, motor suppression had no effect on retention (Experiment 2). These results suggest that the motor system was recruited for the immediate retention of objects, but not for their long-term retention. PMID- 26540143 TI - Two new polyketides from Nocardiopsis lucentensis DSM 44048. AB - Two new polyketides, namely lucentides A (1) and B (2), together with 19 hydroxyprotylonolide (3) were isolated from Nocardiopsis lucentensis DSM 44048. Their structures were elucidated by analysis of their high-resolution mass spectrometry (HR-MS) and 1D, 2D nuclear magnetic resonance (NMR) spectroscopic data. The antibacterial activities of compounds 1-3 were evaluated. PMID- 26540144 TI - Recent Progress in Obtaining Semiconducting Single-Walled Carbon Nanotubes for Transistor Applications. AB - High purity semiconducting single-walled carbon nanotubes (s-SWCNTs) with a narrow diameter distribution are required for high-performance transistors. Achieving this goal is extremely challenging because the as-grown material contains mixtures of s-SWCNTs and metallic- (m-) SWCNTs with wide diameter distributions, typically inadequate for integrated circuits. Since 2000, numerous ex situ methods have been proposed to improve the purity of the s-SWCNTs. The majority of these techniques fail to maintain the quality and integrity of the s SWCNTs with a few notable exceptions. Here, the progress in realizing high purity s-SWCNTs in as-grown and post-processed materials is highlighted. A comparison of transistor parameters (such as on/off ratio and field-effect mobility) obtained from test structures establishes the effectiveness of various methods and suggests opportunities for future improvements. PMID- 26540145 TI - The complete mitochondrial genome of Octopus bimaculatus Verrill, 1883 from the Gulf of California. AB - The complete mitochondrial genome of Octopus bimaculatus is 16 085 bp in length and includes 13 protein-codes genes, 2 ribosomal RNA genes, 22 transfers RNA genes, and a control region. The composition of genome is A (40.9%), T (34.7%), C (16.9%), and G (7.5%). The control region of O. bimaculatus contains a VNTR locus not present in the genomes from other octopus species. A phylogenetic analysis shows a closer relationship between the mitogenomes from O. bimaculatus and O. vulgaris. PMID- 26540146 TI - Foodborne Pathogens Prevention and Sensory Attributes Enhancement in Processed Cheese via Flavoring with Plant Extracts. AB - Cheese contaminations with foodborne bacterial pathogens, and their health outbreaks, are serious worldwide problems that could happen from diverse sources during cheese production or storage. Plants, and their derivatives, were always regarded as the potential natural and safe antimicrobial alternatives for food preservation and improvement. The extracts from many plants, which are commonly used as spices and flavoring agents, were evaluated as antibacterial agents against serious foodborne pathogens, for example Listeria monocytogenes, Salmonella Typhimurium, Staphylococcus aureus, and Escherichia coli O157:H7, using qualitative and quantitative assaying methods. Dairy-based media were also used for evaluating the practical application of plant extracts as antimicrobial agents. Most of the examined plant extracts exhibited remarkable antibacterial activity; the extracts of cinnamon, cloves, garden cress, and lemon grass were the most powerful, either in synthetic or in dairy-based media. Flavoring processed cheese with plant extracts resulted in the enhancement of cheese sensory attributes, for example odor, taste, color, and overall quality, especially in flavored samples with cinnamon, lemon grass, and oregano. It can be concluded that plant extracts are strongly recommended, as powerful and safe antibacterial and flavoring agents, for the preservation and sensory enhancement of processed cheese. PMID- 26540147 TI - Association Between Childhood Hearing Disorders and Tinnitus in Adulthood. AB - IMPORTANCE: The association between childhood hearing disorders and adult tinnitus has not been examined in longitudinal cohort studies. OBJECTIVES: To determine the association between different types of childhood hearing loss and tinnitus in adulthood and evaluate whether tinnitus risk is mediated by adult hearing loss. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of 32 430 adults (aged 20-56 years) who underwent pure-tone audiometry and completed a tinnitus questionnaire in the Nord-Trondelag Hearing Loss Study, which was a part of the Nord-Trondelag Health Study 2 (HUNT2). The study was conducted from January 1, 2014, to April 1, 2015. Data analysis was performed from April 1, 2014, to April 1, 2015. As children, the same individuals had undergone screening audiometry in a longitudinal primary school hearing investigation, including ear, nose, and throat examinations when indicated. INTERVENTIONS: Pure-tone audiometry, questionnaires, and ear, nose, and throat examinations. MAIN OUTCOMES AND MEASURES: Self-reported tinnitus (yes or no) in adulthood measured by questionnaires. RESULTS: Adults who had hearing loss at the time of the school investigation (n = 3026) reported more tinnitus, measured as odds ratio (95% CI), than did adults with normal childhood hearing (n = 29 404) (1.4 [1.3-1.6]). Childhood hearing disorders associated with tinnitus in adulthood included sensorineural hearing loss, chronic suppurative otitis media, and hearing loss associated with a history of recurrent acute otitis media (2.4 [1.9-3.0], 2.4 [1.5-3.9], and 1.6 [1.3-2.0], respectively). These estimates were adjusted for age, sex, and noise exposure in adulthood. After further analyses that included adjustment for adult hearing threshold, none of these childhood hearing disorders remained positively associated with tinnitus. CONCLUSIONS AND RELEVANCE: Childhood hearing disorders associated with tinnitus in adulthood include sensorineural hearing loss, chronic suppurative otitis media, and hearing loss associated with a history of recurrent acute otitis media. After adjustment for the adult hearing threshold, none of the childhood hearing disorders was positively associated with tinnitus. Hence, it appears that these significant associations are mediated or transmitted through adult hearing loss. PMID- 26540148 TI - Association between Intraoperative Hypotension and Myocardial Injury after Vascular Surgery. AB - BACKGROUND: Postoperative myocardial injury occurs frequently after noncardiac surgery and is strongly associated with mortality. Intraoperative hypotension (IOH) is hypothesized to be a possible cause. The aim of this study was to determine the association between IOH and postoperative myocardial injury. METHODS: This cohort study included 890 consecutive patients aged 60 yr or older undergoing vascular surgery from two university centers. The occurrence of myocardial injury was assessed by troponin measurements as part of a postoperative care protocol. IOH was defined by four different thresholds using either relative or absolute values of the mean arterial blood pressure based on previous studies. Either invasive or noninvasive blood pressure measurements were used. Poisson regression analysis was used to determine the association between IOH and postoperative myocardial injury, adjusted for potential clinical confounders and multiple comparisons. RESULTS: Depending on the definition used, IOH occurred in 12 to 81% of the patients. Postoperative myocardial injury occurred in 131 (29%) patients with IOH as defined by a mean arterial pressure less than 60 mmHg, compared with 87 (20%) patients without IOH (P = 0.001). After adjustment for potential confounding factors including mean heart rates, a 40% decrease from the preinduction mean arterial blood pressure with a cumulative duration of more than 30 min was associated with postoperative myocardial injury (relative risk, 1.8; 99% CI, 1.2 to 2.6, P < 0.001). Shorter cumulative durations (less than 30 min) were not associated with myocardial injury. Postoperative myocardial infarction and death within 30 days occurred in 26 (6%) and 17 (4%) patients with IOH as defined by a mean arterial pressure less than 60 mmHg, compared with 12 (3%; P = 0.08) and 15 (3%; P = 0.77) patients without IOH, respectively. CONCLUSIONS: In elderly vascular surgery patients, IOH defined as a 40% decrease from the preinduction mean arterial blood pressure with a cumulative duration of more than 30 min was associated with postoperative myocardial injury. PMID- 26540149 TI - Neuromuscular Blocking Agent Cisatracurium Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-alpha1. AB - BACKGROUND: Neuromuscular blocking agents (NMBAs) bind the nicotinic acetylcholine receptor alpha1 (nAChRalpha1) that also contributes to inflammatory signaling. Thus, the author hypothesized that the use of NMBA mitigates lung injury by improving ventilator synchrony and decreasing inflammatory responses. METHODS: Lung injury was induced by intratracheal instillation of hydrogen chloride in rats that were randomized to receive no NMBA with evidence of asynchronous ventilation (noNMBA/aSYNC, n = 10); no NMBA with synchronous ventilation (noNMBA/SYNC, n = 10); cisatracurium (CIS, n = 10); or pancuronium (PAN, n = 10). Mechanical ventilation was set at a tidal volume of 6 ml/kg and positive end-expiratory pressure 8 cm H2O for 3 h. Human lung epithelial, endothelial, and CD14+ cells were challenged with mechanical stretch, lipopolysaccharide, lung lavage fluids (bronchoalveolar lavage fluid), or plasma obtained from patients (n = 5) with acute respiratory distress syndrome, in the presence or absence of CIS or small-interfering RNA and small hairpin RNA to attenuate the cell expression of nAChRalpha1. RESULTS: The use of CIS and PAN improved respiratory compliance (7.2 +/- 0.7 in noNMBA/aSYNC, 6.6 +/- 0.5 in noNMBA/SYNC, 5.9 +/- 0.3 in CIS, and 5.8 +/- 0.4 cm H2O/l in PAN; P < 0.05), increased PaO2 (140 +/- 54, 209 +/- 46, 269 +/- 31, and 269 +/- 54 mmHg, respectively, P < 0.05), and decreased the plasma levels of tumor necrosis factor alpha (509 +/- 252 in noNMBA, 200 +/- 74 in CIS, and 175 +/- 84 pg/ml in PAN; P < 0.05) and interleukin-6 (5789 +/- 79, 1608 +/- 534, and 2290 +/- 315 pg/ml, respectively; P < 0.05). The use of CIS and PAN or silencing the receptor nAChRalpha1 resulted in decreased cytokine release in the human cells in response to a variety of stimuli mentioned earlier. CONCLUSIONS: The use of NMBA is lung protective through its antiinflammatory properties by blocking the nAChRalpha1. PMID- 26540150 TI - Intraoperative Mean Blood Pressure and Outcome: Is 80 (mmHg) the "New" 60? PMID- 26540151 TI - Searching for Meaningful Topics of Improvement in Anesthesiology. PMID- 26540152 TI - Learning to Estimate Dynamical State with Probabilistic Population Codes. AB - Tracking moving objects, including one's own body, is a fundamental ability of higher organisms, playing a central role in many perceptual and motor tasks. While it is unknown how the brain learns to follow and predict the dynamics of objects, it is known that this process of state estimation can be learned purely from the statistics of noisy observations. When the dynamics are simply linear with additive Gaussian noise, the optimal solution is the well known Kalman filter (KF), the parameters of which can be learned via latent-variable density estimation (the EM algorithm). The brain does not, however, directly manipulate matrices and vectors, but instead appears to represent probability distributions with the firing rates of population of neurons, "probabilistic population codes." We show that a recurrent neural network-a modified form of an exponential family harmonium (EFH)-that takes a linear probabilistic population code as input can learn, without supervision, to estimate the state of a linear dynamical system. After observing a series of population responses (spike counts) to the position of a moving object, the network learns to represent the velocity of the object and forms nearly optimal predictions about the position at the next time-step. This result builds on our previous work showing that a similar network can learn to perform multisensory integration and coordinate transformations for static stimuli. The receptive fields of the trained network also make qualitative predictions about the developing and learning brain: tuning gradually emerges for higher-order dynamical states not explicitly present in the inputs, appearing as delayed tuning for the lower-order states. PMID- 26540153 TI - Interpreting sequence variants in a clinical context. PMID- 26540154 TI - The promise and peril of genomic screening in the general population. AB - PURPOSE: Utilization of sequencing to screen the general population for preventable monogenic conditions is receiving substantial attention because of its potential to decrease morbidity and mortality. However, the selection of which variants to return is a serious implementation challenge. Procedures must be investigated to ensure optimal test characteristics and avoidance of harm from false-positive test results. METHODS: We scanned exome sequences from 478 well phenotyped individuals for potentially pathogenic variants in 17 genes representing 11 conditions that are among the most medically actionable Mendelian disorders in adults. We developed five variant selection algorithms with increasing sensitivity and measured their specificity in these 17 genes. RESULTS: Variant selection algorithms with increasing sensitivity exhibited decreased specificity, and performance was highly dependent on the genes analyzed. The most sensitive algorithm ranged from 88.8 to 99.6% specificity among the 17 genes. CONCLUSION: For conditions with very low prevalence, small reductions in specificity greatly increase false positives. This inescapable test characteristic governs the predictive value of genomic sequencing in the general population. To address this issue, test performance must be evaluated systematically for each condition so that the false negatives and false positives can be tailored for optimal outcomes, depending on the downstream clinical consequences.Genet Med 18 6, 593-599. PMID- 26540155 TI - Clinical follow-up and breast and ovarian cancer screening of true BRCA1/2 noncarriers: a qualitative investigation. AB - PURPOSE: Most women from BRCA1/2 mutation-positive families who did not inherit the familial mutation have breast and ovarian cancer risks similar to those of women of the same age in the general population. However, recent studies suggest that some of these noncarriers may exhibit screening practices that may be considered as excessive compared to general population screening guidelines. Reasons for such tendencies remain largely unknown. This study aims to better understand how the implications of a noncarrier status are explained to these women and how their own realization of this status affects their screening behaviors. METHODS: A qualitative study was conducted with five focus groups (n = 28) in Quebec City and Montreal, Canada. RESULTS: Thematic analysis of the discussions highlighted four major themes: (i) acquiring a noncarrier identity takes place progressively; (ii) noncarriers show a range of opinions about screening; (iii) noncarriers have mixed feelings about the follow-up by their physicians and gynecologists; and (iv) noncarriers need more information in a context where genetics progresses ever more rapidly. CONCLUSION: Our results provide novel insights regarding the physician-patient interaction and the organizational aspects of the health-care system that may significantly impact the cancer screening practices of BRCA1/2 noncarriers.Genet Med 18 6, 627-634. PMID- 26540156 TI - Participant use and communication of findings from exome sequencing: a mixed methods study. AB - PURPOSE: This study investigated how genome sequencing results affect health behaviors, affect, and communication. METHODS: We report on 29 participants who received a sequence result in the ClinSeq study, a cohort of well-educated, postreproductive volunteers. A mixed-methods design was used to explore respondents' use, communication, and perceived utility of results. RESULTS: Most participants (72%) shared their result with at least one health-care provider, and 31% reported subsequent changes in the health care they received. Participants scored high on the Positive Experiences subscale and low on the Distress subscale of a modified version of the Multidimensional Impact of Cancer Risk Assessment. The majority (93%) shared their result with at least one family member. Participants described deriving personal utility from their results. CONCLUSION: This article is the first to describe research participants' reactions to actionable sequencing results. Our findings suggest clinical and personal benefit from receiving sequencing results, both of which may contribute to improved health for the recipients. Given the participants' largely positive or neutral affective responses and disclosure of their results to physicians and relatives, health-care providers should redirect concern from the potential for distress and attend to motivating patients to follow their medical recommendations.Genet Med 18 6, 577-583. PMID- 26540157 TI - Use of External Distractors and the Role of Imaging Prior to Mandibular Distraction in Infants With Isolated Pierre Robin Sequence and Stickler Syndrome. AB - IMPORTANCE: Computed tomographic (CT) scans are often obtained before mandibular distraction osteogenesis in patients with isolated Pierre Robin sequence. There is concern regarding the risk of radiation exposure from CT in children. OBJECTIVE: To evaluate whether preoperative CT is necessary for adequate airway, feeding, and aesthetic outcomes following mandibular distraction with external distraction devices in infants with isolated Pierre Robin sequence. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective review of medical records, infants who underwent mandibular distraction between January 1, 1998, and September 30, 2014, at 2 tertiary children's hospitals were identified using procedure codes. Data analysis was conducted December 1, 2014, to March 31, 2015. Fifty-two patients fit the inclusion criteria of isolated Pierre Robin sequence or Stickler syndrome, of being younger than 9 months at the time of distraction, and of use of external distractors. Forty-two of these infants did not receive preoperative CT imaging. EXPOSURE: Mandibular distraction osteogenesis for isolated Pierre Robin sequence or Stickler syndrome. MAIN OUTCOME MEASURES: Number of infants who were able to avoid tracheostomy or achieve decannulation, who were able to avoid placement or achieve removal of a gastrostomy tube, and in whom there were no intraoperative complications, no open-bite deformity, no malocclusion, no asymmetry, and no postoperative complications. RESULTS: In comparison with the 10 infants who underwent preoperative CT, all 42 of the infants (100%) who did not receive preoperative CT imaging successfully avoided tracheostomy or achieved decannulation (P = .04) and 40 patients (95%) did not require placement of a gastrostomy tube or were able to undergo gastrostomy tube removal postoperatively (P < .001). There were no significant differences between the CT and non-CT groups in the other 5 outcome measures. Two patients (5%) required postoperative gastrostomy tube placement, 2 patients (5%) had minor intraoperative complications that might have been anticipated with CT, 2 patients (5%) demonstrated malocclusion, and 1 infant (2%) had asymmetry at the end of the distraction phase. CONCLUSIONS AND RELEVANCE: This series suggests that the absence of preoperative CT does not compromise functional or aesthetic outcomes in mandibular distraction with external distraction devices in infants with isolated Pierre Robin sequence or Stickler syndrome. This finding has implications for cost containment and reduction of radiation exposure to a vulnerable population. LEVEL OF EVIDENCE: 4. PMID- 26540158 TI - Aneurysm Characteristics Associated with the Rupture Risk of Intracranial Aneurysms: A Self-Controlled Study. AB - This study analyzed the rupture risk of intracranial aneurysms (IAs) according to aneurysm characteristics by comparing the differences between two aneurysms in different locations within the same patient. We utilized this self-controlled model to exclude potential interference from all demographic factors to study the risk factors related to IA rupture. A total of 103 patients were diagnosed with IAs between January 2011 and April 2015 and were enrolled in this study. All enrolled patients had two IAs. One IA (the case) was ruptured, and the other (the control) was unruptured. Aneurysm characteristics, including the presence of a daughter sac, the aneurysm neck, the parent artery diameter, the maximum aneurysm height, the maximum aneurysm width, the location, the aspect ratio (AR, maximum perpendicular height/average neck diameter), the size ratio (SR, maximum aneurysm height/average parent diameter) and the width/height ratio (WH ratio, maximum aneurysm width/maximum aneurysm height), were collected and analyzed to evaluate the rupture risks of the two IAs within each patient and to identify the independent risk factors associated with IA rupture. Multivariate, conditional, backward, stepwise logistic regression analysis was performed to identify the independent risk factors associated with IA rupture. The multivariate analysis identified the presence of a daughter sac (odds ratio [OR], 13.80; 95% confidence interval [CI], 1.65-115.87), a maximum aneurysm height >=7 mm (OR, 4.80; 95% CI, 1.21-18.98), location on the posterior communicating artery (PCOM) or anterior communicating artery (ACOM; OR, 3.09; 95% CI, 1.34-7.11) and SR (OR, 2.13; 95% CI, 1.16-3.91) as factors that were significantly associated with IA rupture. The presence of a daughter sac, the maximum aneurysm height, PCOM or ACOM locations and SR (>1.5+/-0.7) of unruptured IAs were significantly associated with IA rupture. PMID- 26540159 TI - Development of the SAFE Checklist Tool for Assessing Site-Level Threats to Child Protection: Use of Delphi Methods and Application to Two Sites in India. AB - BACKGROUND: The child protection community is increasingly focused on developing tools to assess threats to child protection and the basic security needs and rights of children and families living in adverse circumstances. Although tremendous advances have been made to improve measurement of individual child health status or household functioning for use in low-resource settings, little attention has been paid to a more diverse array of settings in which many children in adversity spend time and how context contributes to threats to child protection. The SAFE model posits that insecurity in any of the following fundamental domains threatens security in the others: Safety/freedom from harm; Access to basic physiological needs and healthcare; Family and connection to others; Education and economic security. Site-level tools are needed in order to monitor the conditions that can dramatically undermine or support healthy child growth, development and emotional and behavioral health. From refugee camps and orphanages to schools and housing complexes, site-level threats exist that are not well captured by commonly used measures of child health and well-being or assessments of single households (e.g., SDQ, HOME). METHODS: The present study presents a methodology and the development of a scale for assessing site-level child protection threats in various settings of adversity. A modified Delphi panel process was enhanced with two stages of expert review in core content areas as well as review by experts in instrument development, and field pilot testing. RESULTS: Field testing in two diverse sites in India-a construction site and a railway station-revealed that the resulting SAFE instrument was sensitive to the differences between the sites from the standpoint of core child protection issues. PMID- 26540160 TI - The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. AB - Cholesterol is essential for diverse cellular functions and cellular and whole body cholesterol homeostasis is highly controlled. Cholesterol can also influence cellular susceptibility to injury. The connection between cholesterol metabolism and inflammation is exemplified by the Tm7sf2 gene, the absence of which reveals an essential role in cholesterol biosynthesis under stress conditions but also results in an inflammatory phenotype, i.e. NF-kappaB activation and TNFalpha up regulation. Here, by using Tm7sf2+/+and Tm7sf2-/- mice, we investigated whether the Tm7sf2 gene, through its role in cholesterol biosynthesis under stress conditions, is involved in the renal failure induced by the administration of LPS. We found that the loss of Tm7sf2 gene results in significantly reduced blood urea nitrogen levels accompanied by decreased renal inflammatory response and neutral lipid accumulation. The increased expression of fatty acids catabolic enzymes reduces the need of the renal autophagy, a known crucial nutrient-sensing pathway in lipid metabolism. Moreover, we observed that the Tm7sf2 insufficiency is responsible for the inhibition of the NF-kappaB signalling thus dampening the inflammatory response and leading to a reduced renal damage. These results suggest a pivotal role for Tm7sf2 in renal inflammatory and lipotoxic response under endotoxemic conditions. PMID- 26540161 TI - Systemic Resistance to Powdery Mildew in Brassica napus (AACC) and Raphanus alboglabra (RRCC) by Trichoderma harzianum TH12. AB - Trichoderma harzianum TH12 is a microbial pesticide for certain rapeseed diseases. The mechanism of systemic resistance induced by TH12 or its cell-free culture filtrate (CF) in Brassica napus (AACC) and Raphanus alboglabra (RRCC) to powdery mildew disease caused by ascomycete Erysiphe cruciferarum was investigated. In this study, we conducted the first large-scale global study on the cellular and molecular aspects of B. napus and R. alboglabra infected with E. cruciferarum. The histological study showed the resistance of R. alboglabra to powdery mildew disease. The growth of fungal colonies was not observed on R. alboglabra leaves at 1, 2, 4, 6, 8, and 10 days post-inoculation (dpi), whereas this was clearly observed on B. napus leaves after 6 dpi. In addition, the gene expression of six plant defense-related genes, namely, PR-1, PR-2 (a marker for SA signaling), PR-3, PDF 1.2 (a marker for JA/ET signaling), CHI620, and CHI570, for both genotypes were analyzed in the leaves of B. napus and R. alboglabra after treatment with TH12 or CF and compared with the non-treated ones. The qRT PCR results showed that the PR-1 and PR-2 expression levels increased in E. cruciferarum-infected leaves, but decreased in the TH12-treated leaves compared with leaves treated with CF. The expression levels of PR-3 and PDF1.2 decreased in plants infected by E. cruciferarum. However, expression levels increased when the leaves were treated with TH12. For the first time, we disclosed the nature of gene expression in B. napus and R. alboglabra to explore the resistance pathways in the leaves of both genotypes infected and non-infected by powdery mildew and inoculated or non-inoculated with elicitor factors. Results suggested that R. alboglabra exhibited resistance to powdery mildew disease, and the application of T. harzianum and its CF are a useful tool to facilitate new protection methods for resist or susceptible plants. PMID- 26540162 TI - dRNA-Seq Reveals Genomewide TSSs and Noncoding RNAs of Plant Beneficial Rhizobacterium Bacillus amyloliquefaciens FZB42. AB - Bacillus amyloliquefaciens subsp. plantarum FZB42 is a representative of Gram positive plant-growth-promoting rhizobacteria (PGPR) that inhabit plant root environments. In order to better understand the molecular mechanisms of bacteria plant symbiosis, we have systematically analyzed the primary transcriptome of strain FZB42 grown under rhizosphere-mimicking conditions using differential RNA sequencing (dRNA-seq). Our analysis revealed 4,877 transcription start sites for protein-coding genes, identified genes differentially expressed under different growth conditions, and corrected many previously mis-annotated genes. We also identified a large number of riboswitches and cis-encoded antisense RNAs, as well as trans-encoded small noncoding RNAs that may play important roles in the gene regulation of Bacillus. Overall, our analyses provided a landscape of Bacillus primary transcriptome and improved the knowledge of rhizobacteria-host interactions. PMID- 26540163 TI - Practical Telemedicine for Veterans with Persistently Poor Diabetes Control: A Randomized Pilot Trial. AB - BACKGROUND: Telemedicine-based diabetes management improves outcomes versus clinic care but is seldom implemented by healthcare systems. In order to advance telemedicine-based management as a practical option for veterans with persistent poorly controlled diabetes mellitus (PPDM) despite clinic-based care, we evaluated a comprehensive telemedicine intervention that we specifically designed for delivery using existing Veterans Health Administration (VHA) clinical staffing and equipment. MATERIALS AND METHODS: We conducted a 6-month randomized trial among 50 veterans with PPDM; all maintained hemoglobin A1c (HbA1c) levels continuously >9.0% for >1 year despite clinic-based management. Participants received usual care or a telemedicine intervention combining telemonitoring, medication management, self-management support, and depression management; existing VHA clinical staff delivered the intervention. Using linear mixed models, we examined HbA1c, diabetes self-care (measured by the Self-Care Inventory-Revised questionnaire), depression, and blood pressure. RESULTS: At baseline, the model-estimated common HbA1c intercept was 10.5%. By 6 months, estimated HbA1c had improved by 1.3% for intervention participants and 0.3% for usual care (estimated difference, -1.0%, 95% confidence interval [CI], -2.0%, 0.0%; p = 0.050). Intervention participants' diabetes self-care (estimated difference, 7.0; 95% CI, 0.1, 14.0; p = 0.047), systolic blood pressure (-7.7 mm Hg; 95% CI, -14.8, -0.6; p = 0.035), and diastolic blood pressure (-5.6 mm Hg; 95% CI, -9.9, -1.2; p = 0.013) were improved versus usual care by 6 months. Depressive symptoms were similar between groups. CONCLUSIONS: A comprehensive telemedicine intervention improved outcomes among veterans with PPDM despite clinic-based care. Because we specifically designed this intervention with scalability in mind, it may represent a practical, real-world strategy to reduce the burden of poor diabetes control among veterans. PMID- 26540164 TI - ZFX is a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma. AB - BACKGROUND: This study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients. MATERIAL AND METHODS: The expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis. RESULTS: The qRT-PCR result showed that the ZFX was significantly up regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033-24.180). CONCLUSIONS: Our findings show that ZFX could be considered as a predictor for prognosis of RCC patients. PMID- 26540165 TI - Predictive Factors of Patient Satisfaction with Pharmacy Services in South Korea: A Cross-Sectional Study of National Level Data. AB - OBJECTIVES: Patient satisfaction has emerged as a prerequisite to improving patients' health behaviors leading to better health care outcomes. This study was to identify predictive determinants for patient satisfaction with pharmacy services using national-level data. METHODS: A cross-sectional evaluation was conducted using 2008 Korean National Health and Nutrition Examination Survey (KNHANES) data. To assess the predictive factors for patient satisfaction with pharmacy services, an ordinal logistic regression model was conducted adjusting for patient characteristics, clinical comorbidities, and perception of health. RESULTS: A total of 9,744 people, a representative sample of 48.2 million Koreans, participated in the 2008 KNHANES, of whom 2,188 (23.6%) reported visits to pharmacy within the last 2 weeks prior to the survey. Of the patients who visited the pharmacy, 74.6% reported to be either "very satisfied" or "satisfied," and 25.4% responded as being "neutral," "dissatisfied," or "very dissatisfied." A multivariate ordinal logistic regression analysis with weighted observations revealed that patients with fair perception of health (adjusted OR 1.32; 95% CI 1.01-1.74; p<0.05) and those with middle to low family incomes (adjusted OR 1.34; 95% CI 1.02-1.76; p<0.05) were more likely to be satisfied with pharmacy services, and employment-based insurers were less likely to be satisfied with pharmacy services (adjusted OR 0.80; 95% CI 0.65-0.97; p<0.05). CONCLUSION: Our findings indicated that three out of four patients expressed satisfaction toward pharmacy services. Middle to low family incomes, fair perception of health, and employee insured individuals were significant predictors of patient satisfaction with pharmacy services. PMID- 26540166 TI - Study of Malformin C, a Fungal Source Cyclic Pentapeptide, as an Anti-Cancer Drug. AB - Malformin C, a fungal cyclic pentapeptide, has been claimed to have anti-cancer potential, but no in vivo study was available to substantiate this property. Therefore, we conducted in vitro and in vivo experiments to investigate its anti cancer effects and toxicity. Our studies showed Malformin C inhibited Colon 38 and HCT 116 cell growth dose-dependently with an IC50 of 0.27+/-0.07MUM and 0.18+/-0.023MUM respectively. This inhibition was explicated by Malformin C's effect on G2/M arrest. Moreover, we observed up-regulated expression of phospho histone H2A.X, p53, cleaved CASPASE 3 and LC3 after Malformin C treatment, while the apoptosis assay indicated an increased population of necrotic and late apoptotic cells. In vivo, the pathological study exhibited the acute toxicity of Malformin C at lethal dosage in BDF1 mice might be caused by an acute yet subtle inflammatory response, consistent with elevated IL-6 in the plasma cytokine assay. Further anti-tumor and toxicity experiments proved that 0.3mg/kg injected weekly was the best therapeutic dosage of Malformin C in Colon 38 xenografted BDF1 mice, whereas 0.1mg/kg every other day showed no effect with higher resistance, and 0.9mg/kg per week either led to fatal toxicity in seven-week old mice or displayed no advantage over 0.3mg/kg group in nine-week old mice. Overall, we conclude that Malformin C arrests Colon 38 cells in G2/M phase and induces multiple forms of cell death through necrosis, apoptosis and autophagy. Malformin C has potent cell growth inhibition activity, but the therapeutic index is too low to be an anti-cancer drug. PMID- 26540167 TI - Effect of a Selective Mas Receptor Agonist in Cerebral Ischemia In Vitro and In Vivo. AB - Functional modulation of the non-AT1R arm of the renin-angiotensin system, such as via AT2R activation, is known to improve stroke outcome. However, the relevance of the Mas receptor, which along with the AT2R forms the protective arm of the renin-angiotensin system, as a target in stroke is unclear. Here we tested the efficacy of a selective MasR agonist, AVE0991, in in vitro and in vivo models of ischemic stroke. Primary cortical neurons were cultured from E15-17 mouse embryos for 7-9 d, subjected to glucose deprivation for 24 h alone or with test drugs, and percentage cell death was determined using trypan blue exclusion assay. Additionally, adult male mice were subjected to 1 h middle cerebral artery occlusion and were administered either vehicle or AVE0991 (20 mg/kg i.p.) at the commencement of 23 h reperfusion. Some animals were also treated with the MasR antagonist, A779 (80 mg/kg i.p.) 1 h prior to surgery. Twenty-four h after MCAo, neurological deficits, locomotor activity and motor coordination were assessed in vivo, and infarct and edema volumes estimated from brain sections. Following glucose deprivation, application of AVE0991 (10-8 M to 10-6 M) reduced neuronal cell death by ~60% (P<0.05), an effect prevented by the MasR antagonist. By contrast, AVE0991 administration in vivo had no effect on functional or histological outcomes at 24 h following stroke. These findings indicate that the classical MasR agonist, AVE0991, can directly protect neurons from injury following glucose-deprivation. However, this effect does not translate into an improved outcome in vivo when administered systemically following stroke. PMID- 26540168 TI - A Cross-Sectional Retrospective Analysis of the Racial and Geographic Variations in Cataract Surgery. AB - BACKGROUND: Cataract surgery is the most common surgery performed on beneficiaries of Medicare, accounting for more than $3.4 billion in annual expenditures. The purpose of this study is to examine racial and geographic variations in cataract surgery rates and determine the association between the racial composition of the community population and the racial disparity in the likelihood of receiving necessary cataract surgery. METHODS: Using the national prevalence rates from the National Institute of Eye Health and the 2010 Healthcare Cost and Utilization Project-Florida State Ambulatory Surgery Database, we determined the estimated cases of cataract and the actual number of cataract procedures performed, on four race/gender determined groups aged 65 and over in the state of Florida in 2010. The utilization rates and disparity ratios were also calculated for each Florida county. The counties were segmented into groups based on their racial composition. The association between racial composition and disparity ratios in receiving necessary cataract surgery was examined. The Geographic Information System was used to display county-level geospatial relationships. RESULTS: African-Americans have a lower gender-specific cataract prevalence (African-American male = 0.246, African-American female = 0.392, white male = 0.368, and white female = 0.457), but they are also less likely than whites to receive necessary cataract surgery (utilization rate: African-American male = 7.92%, African-American female = 6.17%, white male = 12.08%, and white female = 10.54%). The statistical results show no overall differences between the disparity ratios and the racial composition of the communities. However, our geospatial analyses revealed a concentration of high racial disparity/high white population counties largely along the West Coast and South Central portion of the state. CONCLUSIONS: There are racial differences in the likelihood of receiving necessary cataract surgery. However, there is no significant statewide association between the racial composition of the community population and the racial disparity in the likelihood of receiving necessary cataract surgery. Geospatial techniques did, however, identify subpopulations of interest which were not otherwise identifiable with typical statistical approaches, nor consistent with their conclusions. PMID- 26540169 TI - Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome due to germline mutations in either TSC1 or TSC2. 10-15% of TSC individuals have no mutation identified (NMI) after thorough conventional molecular diagnostic assessment. 53 TSC subjects who were NMI were studied using next generation sequencing to search for mutations in these genes. Blood/saliva DNA including parental samples were available from all subjects, and skin tumor biopsy DNA was available from six subjects. We identified mutations in 45 of 53 subjects (85%). Mosaicism was observed in the majority (26 of 45, 58%), and intronic mutations were also unusually common, seen in 18 of 45 subjects (40%). Seventeen (38%) mutations were seen at an allele frequency < 5%, five at an allele frequency < 1%, and two were identified in skin tumor biopsies only, and were not seen at appreciable frequency in blood or saliva DNA. These findings illuminate the extent of mosaicism in TSC, indicate the importance of full gene coverage and next generation sequencing for mutation detection, show that analysis of TSC-related tumors can increase the mutation detection rate, indicate that it is not likely that a third TSC gene exists, and enable provision of genetic counseling to the substantial population of TSC individuals who are currently NMI. PMID- 26540171 TI - Degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan Is Not a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy. AB - BACKGROUND: Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control. FINDINGS: The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information. CONCLUSIONS: In this cohort of predominately high-risk localised prostate cancer, rectal distension had no significant impact on PSA relapse. We suggest that regular imaging during radiotherapy negates the risk caused by rectal distension on local treatment failure. PMID- 26540170 TI - Serum-Free Suspension Culture of MDCK Cells for Production of Influenza H1N1 Vaccines. AB - Development of serum-free suspension cell culture processes is very important for influenza vaccine production. Previously, we developed a MDCK suspension cell line in a serum-free medium. In the present study, the growth kinetics of suspension MDCK cells and influenza virus production in the serum-free medium were investigated, in comparison with those of adherent MDCK cells in both serum containing and serum-free medium. It was found that the serum-free medium supported the stable subculture and growth of both adherent and suspension cells. In batch culture, for both cell lines, the growth kinetics in the serum-free medium was comparable with those in the serum-containing medium and a commercialized serum-free medium. In the serum-free medium, peak viable cell density (VCD), haemagglutinin (HA) and median tissue culture infective dose (TCID50) titers of the two cell lines reached 4.51*106 cells/mL, 2.94Log10(HAU/50 MUL) and 8.49Log10(virions/mL), and 5.97*106 cells/mL, 3.88Log10(HAU/50 MUL), and 10.34Log10(virions/mL), respectively. While virus yield of adherent cells in the serum-free medium was similar to that in the serum-containing medium, suspension culture in the serum-free medium showed a higher virus yield than adherent cells in the serum-containing medium and suspension cells in the commercialized serum free medium. However, the percentage of infectious viruses was lower for suspension culture in the serum-free medium. These results demonstrate the great potential of this suspension MDCK cell line in serum-free medium for influenza vaccine production and further improvements are warranted. PMID- 26540172 TI - Next-Generation Sequencing in Oncology in the Era of Precision Medicine. PMID- 26540174 TI - IFN-gamma Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage. AB - Treatment of interferon-gamma (IFN-gamma) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-gamma signaling, this study investigated the link between autophagy and IFN-gamma cytotoxicity. In A549 human lung cancer cells, IFN-gamma treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6. Furthermore, IFN-gamma signaling controlled mimic ETosis through a mechanism involving an autophagy- and Fas-associated protein with death domain-controlled caspase-8/-3 activation. Following caspase-mediated lamin degradation, IFN-gamma caused DNA damage-associated ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM)-regulated mimic ETosis. Upon ATR/ATM signaling, peptidyl arginine deiminase 4 (PAD4)-mediated histone 3 citrullination promoted mimic ETosis. Such IFN-gamma-induced effects were defective in PC14PE6/AS2 human lung cancer cells, which were unsusceptible to IFN-gamma induced autophagy. Due to autophagy-based caspase cascade activation, IFN-gamma triggers unconventional caspase-mediated DNA damage, followed by ATR/ATM regulated PAD4-mediated histone citrullination during mimic ETosis in lung epithelial malignancy. PMID- 26540173 TI - Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. AB - BACKGROUND: Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS: The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS: Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age >=60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m(2) , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS: In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. PMID- 26540175 TI - Hereditary Angioedema in Swedish Adults: Report From the National Cohort. AB - Hereditary angioedema (HAE) is rare, disabling and sometimes life-threatening. The aim of this study is to describe its prevalence, symptomatology and treatment in Sweden. A total of 146 patients were identified; 110 adults and 36 children with HAE type I (n = 136) or II (n = 10), giving a minimal HAE prevalence of 1.54/100,000. All patients received a written questionnaire followed by a structured telephone interview. This report focuses on the 102 adults who responded. Females reported 19 attacks in the previous year vs. 9 for males (p < 0.01), and females reported 10 days of sick leave vs. 4 days for males (p < 0.05). For all treated acute attacks, plasma-derived C1-inhibitor concentrate (pdC1INH) (used in 27% of patients) had a good effect. For maintenance treatment, 43% used attenuated androgens and 8% used pdC1INH, which reduced their attack rate by more than 50%. In conclusion, the minimal HAE prevalence in Sweden was 1.54/100,000. HAE affected females more severely. Attenuated androgens and pdC1INH had a good effect on preventing attacks. PMID- 26540177 TI - Serologic Evidence of Flavivirus Infections in Peridomestic Rodents in Merida, Mexico. AB - We conducted surveillance for flavivirus infection in peridomestic rodents in Merida, Mexico in 2011-12. We captured 161 rodents inside private residences, using Sherman traps, including 86 house mice (Mus musculus) and 75 black rats (Rattus rattus). Serum from each animal was assayed by plaque reduction neutralization test (PRNT) using two vertebrate-specific flaviviruses (Apoi and Modoc viruses) and five mosquito-borne flaviviruses (dengue 2, dengue 4, St. Louis encephalitis virus, West Nile, and yellow fever viruses). Sixty-one (37.9%) rodents had antibodies that neutralized at least one virus. Prevalences for flaviviruses were 64.0% and 15.1% for black rats and house mice, respectively. None of the PRNT90 titers exceeded 80, and often they were highest for Modoc virus. These data suggest that a subset of rodents had been infected with Modoc virus or a closely related flavivirus that was not included in the PRNT analysis. PMID- 26540176 TI - Systemic Problems: A perspective on stem cell aging and rejuvenation. AB - This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a "silver bullet" putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are "beyond parabiosis" for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging. PMID- 26540178 TI - PAPILLOMAVIRUS IN HEALTHY SKIN AND MUCOSA OF WILD RUMINANTS IN THE ITALIAN ALPS. AB - We investigated healthy skin and mucosal specimens of wild ruminants in the Italian Alps. We identified bovine papillomavirus (BPV)-2 DNA in the healthy skin of wild ruminants and documented coinfection of BPV-1 and Cervus elaphus papillomavirus (CePV)-1 in a healthy red deer (Cervus elaphus). We also demonstrated cross-infections of BPVs of the genus Xipapillomavirus, both as single virus infection and also in association with Deltapapillomavirus types 1 and 2, confirming that host tropism of papillomaviruses is not as species specific as previously thought. Our results suggest that subclinical infections could be linked to the presence of domestic ruminants sharing the same habitat with wild species and that the wildlife may act as a reservoir for papillomaviruses affecting domestic species. PMID- 26540179 TI - ECOLOGICAL DETERMINANTS OF AVIAN INFLUENZA VIRUS, WEST NILE VIRUS, AND AVIAN PARAMYXOVIRUS INFECTION AND ANTIBODY STATUS IN BLUE-WINGED TEAL (ANAS DISCORS) IN THE CANADIAN PRAIRIES. AB - The Canadian prairies are one of the most important breeding and staging areas for migratory waterfowl in North America. Hundreds of thousands of waterfowl of numerous species from multiple flyways converge in and disperse from this region annually; therefore this region may be a key area for potential intra- and interspecific spread of infectious pathogens among migratory waterfowl in the Americas. Using Blue-winged Teal (Anas discors, BWTE), which have the most extensive migratory range among waterfowl species, we investigated ecologic risk factors for infection and antibody status to avian influenza virus (AIV), West Nile virus (WNV), and avian paramyxovirus-1 (APMV-1) in the three prairie provinces (Alberta, Saskatchewan, and Manitoba) prior to fall migration. We used generalized linear models to examine infection or evidence of exposure in relation to host (age, sex, body condition, exposure to other infections), spatiotemporal (year, province), population-level (local population densities of BWTE, total waterfowl densities), and environmental (local pond densities) factors. The probability of AIV infection in BWTE was associated with host factors (e.g., age and antibody status), population-level factors (e.g., local BWTE population density), and year. An interaction between age and AIV antibody status showed that hatch year birds with antibodies to AIV were more likely to be infected, suggesting an antibody response to an active infection. Infection with AIV was positively associated with local BWTE density, supporting the hypothesis of density-dependent transmission. The presence of antibodies to WNV and APMV-1 was positively associated with age and varied among years. Furthermore, the probability of being WNV antibody positive was positively associated with pond density rather than host population density, likely because ponds provide suitable breeding habitat for mosquitoes, the primary vectors for transmission. Our findings highlight the importance of spatiotemporal, environmental, and host factors at the individual and population levels, all of which may influence dynamics of these and other viruses in wild waterfowl populations. PMID- 26540180 TI - Mountain Yellow-legged Frogs (Rana muscosa) did not Produce Detectable Antibodies in Immunization Experiments with Batrachochytrium dendrobatidis. AB - Chytridiomycosis is a devastating infectious disease of amphibians caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). A growing number of studies have examined the role of amphibian adaptive immunity in response to this pathogen, with varying degrees of immune activation reported. Here we present immunologic data for the mountain yellow-legged frog, Rana muscosa, and the Sierra Nevada yellow-legged frog, Rana sierrae, which are two endangered and ecologically important species experiencing Bd-inflicted declines. Previous studies on these species that examined transcriptional response during Bd infection, and the effective of immunization, provided little evidence of immune activation to Bd. However, the studies did not directly assay immune effectors in the frog hosts. We performed experiments to examine antibody production, which is a hallmark of systemic adaptive immune activation. We used controlled laboratory experiments and enzyme-linked immunosorbent assays to examine the antibody response to Bd immunization and live Bd exposure. Rana muscosa and R. sierrae individuals did not produce detectable antibodies with the capacity to bind to denatured Bd antigens under our experimental conditions. While we cannot rule out antibody response to Bd in these species, our results suggest weak, poor, or inefficient production of antibodies to denatured Bd antigens. Our findings are consistent with susceptibility to chytridiomycosis in these species and suggest additional work is needed to characterize the potential for adaptive immunity. PMID- 26540181 TI - Novel Papillomaviral Sequence Detected within Epidermal Plaques in a Wolf (Canis lupus). AB - We describe numerous pale plaques affecting the inguinal skin of a grey wolf (Canis lupus). Histologically, these were consistent with papillomaviral plaques. Immunohistochemistry confirmed papillomavirus antigens, and partial sequencing of the L1 gene suggests this is a novel papillomavirus most-closely related to Canis familiaris Papillomavirus 5. PMID- 26540182 TI - Chemical enhancement of fingermark in blood on thermal paper. AB - Chemical enhancement methods for fingermark in blood deposited on the surface of a thermal paper substrate were examined. The blood-sensitive reagents compared were LCV (leuco crystal violet), Amido black and Hungarian red. Fingermark in blood on the surface of thermal paper can be fixed with 2% 5-sulfosalicylic acid solution. LCV was found as an inadequate blood staining reagent because of bubbling, diffusion, and blurring on the surface of thermal paper. Hungarian red was also an inadequate blood staining reagent because excess Hungarian red on the surface of thermal paper was not washed away in the de-staining procedure. Amido black was the best staining reagent among three staining reagents compared. The maximum dilution ratio visible to the naked eye after Amido black staining was 1 in 80 for the thermally sensitive surface and 1 in 20 for the thermally non sensitive surface. PMID- 26540183 TI - Practises and controversies in the management of asymptomatic aneurysms: Results of an international survey. AB - BACKGROUND: Asymptomatic aneurysms that are increasingly discovered on cranial diagnostic imaging are a growing management dilemma. Large-scale studies have shown that in most instances, conservative management is appropriate for the majority of patients with aneurysms less than 7 mm in maximum diameter. It is unclear whether international practise mirrors practise in these large trials. OBJECTIVE: To determine how neurosurgeons around the world manage patients with asymptomatic aneurysms. METHODS: Electronic survey of 283 clinicians managing patients with aneurysms using a 55-item questionnaire detailing characteristics of their experience, their hospitals and their present and future practises and insights regarding the management of patients with intracerebral aneurysms. RESULTS: The 203 neurosurgeons (72%) who responded had a median of 17 years of practise with aneurysms and managed a median of 25 aneurysms annually. The majority of neurosurgeons endorsed treatment of all asymptomatic aneurysms regardless of size. Only four out of 10 neurosurgeons would manage patients with 4 mm anterior communicating artery or middle cerebral artery aneurysms non surgically, whereas fewer than 2% would conservatively manage asymptomatic patients with 10 or 16 mm aneurysms. Neurosurgeons were split as to the recommended techniques for asymptomatic aneurysms of 10 or 16 mm with about half of them electing clipping and half coiling for ACoA and nearly three quarters favouring clipping for the MCA aneurysm. Although international differences exist between Europe, North America and the rest of the world, most state that their choice of treatment related to decisions around what option would provide the best neurological outcome and prevention of long-term bleeding. CONCLUSION: Despite large trials supporting the management of small asymptomatic aneurysms, most neurosurgeons internationally chooses to treat them with surgery or endovascular means. Since clinicians use a number of factors beyond the maximum diameter when considering treatment options, future trials should consider these factors in their design. PMID- 26540185 TI - In Vitro Inactivation of Kudoa septempunctata Spores Infecting the Muscle of Olive Flounder Paralichthys olivaceus. AB - Kudoa septempunctata, a myxosporean parasite infecting the trunk muscles of olive flounder (Paralichthys olivaceus), has been recently reported to be the causative agent of a type of food poisoning in humans. Patients exhibited acute diarrhea and vomiting after ingestion of the raw flesh of infected flounder. A recent increase in the number of food-poisoning cases has prompted us to develop a control strategy of this parasite. In this study, we evaluated the efficacy of several temperature and chemical treatments for inactivating K. septempunctata spores in vitro using the vital staining assay with the fluorescent dyes Hoechst 33342 and propidium iodide (PI). Screening tests of treatment methods against K. septempunctata suggested that 25% ethanol for 5 min, 80 degrees C for 10 s, limonene at 10 MUL/mL for 5 min, and salinities at 00/00 and 1600/00 for 5 min were effective for killing spores. To verify toxicity loss in K. septempunctata spores after the treatments, tight junction barrier integrity assays with Caco-2 cells were conducted. The results of the Caco-2 assays corresponded well with those of the Hoechst 33342-PI staining assay. Further studies are required to determine a practical treatment procedure for inactivating spores considering the treatment application in the production process of cultured olive flounder. PMID- 26540184 TI - Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis. AB - Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination. PMID- 26540187 TI - Increased deaths from gastric cancer in communities living close to waste landfills. AB - BACKGROUND: Municipal waste landfills (MWLs) have been linked with some malignancies, but data about gastric cancer (GC) are still uncertain. METHODS: Number of deaths from GC, death rates, and odds ratios (ORs) were calculated considering all residents in the 258 towns in the Apulia Region (4,099,547 subjects, years 2006-2009), living within 3 km from each of the 16 regional MWLs (n = 716,404) or in control areas (n = 3,383,143). RESULTS: Males living close to MWLs showed a higher death rate for GC, a twofold higher mean number of GC deaths and higher adjusted ORs of GC, compared with controls areas. CONCLUSIONS: In a large population and over a wide time period, an increased risk of death from GC has been shown in males living in communities close to MWLs. Primary prevention policies acting through more sustainable waste management might probably partially reduce deaths from GC in areas with MWLs. PMID- 26540186 TI - Nitric Oxide Down-Regulates Topoisomerase I and Induces Camptothecin Resistance in Human Breast MCF-7 Tumor Cells. AB - Camptothecin (CPT), a topoisomerase I poison, is an important drug for the treatment of solid tumors in the clinic. Nitric oxide (.NO), a physiological signaling molecule, is involved in many cellular functions, including cell proliferation, survival and death. We have previously shown that .NO plays a significant role in the detoxification of etoposide (VP-16), a topoisomerase II poison in vitro and in human melanoma cells. .NO/.NO-derived species are reported to modulate activity of several important cellular proteins. As topoisomerases contain a number of free sulfhydryl groups which may be targets of .NO/.NO derived species, we have investigated the roles of .NO/.NO-derived species in the stability and activity of topo I. Here we show that .NO/.NO-derived species induces a significant down-regulation of topoisomerase I protein via the ubiquitin/26S proteasome pathway in human colon (HT-29) and breast (MCF-7) cancer cell lines. Importantly, .NO treatment induced a significant resistance to CPT only in MCF-7 cells. This resistance to CPT did not result from loss of topoisomerase I activity as there were no differences in topoisomerase I-induced DNA cleavage in vitro or in tumor cells, but resulted from the stabilization/induction of bcl2 protein. This up-regulation of bcl2 protein in MCF-7 cells was wtp53 dependent as pifithrine-alpha, a small molecule inhibitor of wtp53 function, completely reversed CPT resistance, suggesting that wtp53 and bcl2 proteins played important roles in CPT resistance. Because tumors in vivo are heterogeneous and contaminated by infiltrating macrophages, .NO-induced down regulation of topoisomerase I protein combined with bcl2 protein stabilization could render certain tumors highly resistant to CPT and drugs derived from it in the clinic. PMID- 26540188 TI - Effects of sulphamethazine and zinc on the functional diversity of microbial communities during composting. AB - The changes in the functional diversity of the microbial community in a compost matrix with a single or compound addition of zinc (Zn; 0, 600, and 1800 mg/kg) and sulphamethazine (SM2; 0, 1, and 25 mg/kg) were studied with the Biolog method during composting. The microbial community was extracted from the compost matrix comprising swine manure and wheat straw at day 6 (themophilic period) and day 25 (mature period) of composting. Results proved that the Shannon index, average well-colour development, and substrate utilization significantly decreased as the concentrations of SM2 and Zn increased on day 6. The negative effect of the combined addition of SM2 and Zn was lower than that of the individual addition of SM2 and Zn. On day 25, the inhibition effect disappeared, and microbial metabolic activities were higher than those on day 6. The effects of SM2 and Zn could be further differentiated via the principal component analysis (PCA) and cluster analysis. On day 6, the treatments were divided into three groups by PC1 and PC2. The separation of the different treatments in the PCA plots became increasingly apparent on day 25. In conclusion, the effects of SM2 and Zn on the microbial community during composting became evident in the themophilic period and that the microbial activity recovered in the mature period. The combination of SM2 and Zn decreased the inhibition with the addition of individual additive. PMID- 26540189 TI - Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy. AB - BACKGROUND: Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. MATERIALS AND METHODS: We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 MUg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 MUg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. RESULTS: In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper measured data with the applied two-dimensional mathematical model. CONCLUSION: Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. PMID- 26540190 TI - Risk Factors for Lobar and Non-Lobar Intracerebral Hemorrhage in Patients with Vascular Disease. AB - INTRODUCTION: Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. METHODS: In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. RESULTS: During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH. CONCLUSION: This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH. PMID- 26540191 TI - Detection of sarcastic speech: The role of the right hemisphere in ambiguity resolution. AB - Two experiments were conducted to determine if the right hemisphere (RH) plays a central role in understanding sarcasm. In Experiment 1, 48 participants completed a target detection task using dichotically presented phrases that were sincere (message compatible), sarcastic (conflicting semantic and prosodic message), or neutral (no emotional prosody). Sarcastic phrases presented to the left ear (LE)/RH produced faster response times than sarcastic phrases presented to the right ear/left hemisphere. Accuracy results indicated an overall LE/RH advantage for detecting both sarcastic and sincere phrases. Experiment 2 utilized the same task with the addition of event-related potential recording. There was a reliable N400 seen in response to the sarcastic phrases, but only with LE/RH presentation. These results suggest that the RH is particularly sensitive to the mismatch between semantic and prosodic information characterized by sarcasm. PMID- 26540192 TI - Insights into the molecular interactions of thymoquinone with histone deacetylase: evaluation of the therapeutic intervention potential against breast cancer. AB - Many HDAC inhibitors have passed through the gateway of clinical trials. However, they have limited therapeutic implications due to their pleiotropic pharmaceutical properties and off-target effects. In view of this, dietary active phytochemicals were evaluated. Based upon the chemical and structural insights of HDAC active pockets, thymoquinone (TQ) was investigated to uncover its active participation in HDAC inhibition. The synergistic analysis of docking and molecular dynamics simulation disclosed the elementary interaction and stability of TQ with human HDACs. The in silico findings were corroborated with an in vitro analysis, demonstrating the efficient role of TQ in the attenuation of global HDAC activity. Furthermore, TQ also elicited downstream effects of HDAC inhibition: reactivation of HDAC target genes (p21 and Maspin), induction of the pro-apoptotic gene Bax, down regulation of the anti-apoptotic gene Bcl-2 and arrest of the cell cycle at the G2/M phase. Finally, the result of a higher cytotoxicity of TQ towards MCF-7 breast cancer cells in comparison to normal cells indicates the potential of TQ to be an anticancer drug. PMID- 26540193 TI - Carbon Nanotubes with Tailored Density of Electronic States for Electrochemical Applications. AB - The density of electronic states (DOS) is an intrinsic electronic property that works conclusively in the electrochemistry of carbon materials. However, seldom has it been reported how the DOS at the Fermi level influences the electrochemical activity. In this work, we synthesized partially and fully unzipped carbon nanotubes by longitudinally unzipping pristine carbon nanotubes (CNTs). We then studied the electrochemical activity and biosensitivity of carbon materials by means of the CNTs and their derivatives to elucidate the effect of the DOS on their electrochemical performances. Tailoring of the DOS for the CNT derivatives could be conveniently realized by varying the sp(2)/sp(3) ratio (i.e., graphite concentration) through manipulating the oxidative unzipping degree. Despite the diverse electron transfer mechanisms and influence factors of the four investigated redox probes (IrCl6(2-), [Fe(CN)6](3-), Fe(3+), and ascorbic acid), the CNT derivatives exhibited consistent kinetic behaviors, wherein CNTs with a high DOS showed superior electrochemical response compared with partially and fully unzipped carbon nanotubes. For biological detection, the CNTs could simultaneously distinguish ascorbic acid, dopamine, and uric acid, while the three CNT derivatives could all differentiate phenethylamine and epinephrine existed in the newborn calf serum. Moreover, the three CNT derivatives all presented wide linear detection ranges with high sensitivities for dopamine, phenethylamine, and epinephrine. PMID- 26540194 TI - Masking Release in Children and Adults With Hearing Loss When Using Amplification. AB - PURPOSE: This study compared masking release for adults and children with normal hearing and hearing loss. For the participants with hearing loss, masking release using simulated hearing aid amplification with 2 different compression speeds (slow, fast) was compared. METHOD: Sentence recognition in unmodulated noise was compared with recognition in modulated noise (masking release). Recognition was measured for participants with hearing loss using individualized amplification via the hearing-aid simulator. RESULTS: Adults with hearing loss showed greater masking release than the children with hearing loss. Average masking release was small (1 dB) and did not depend on hearing status. Masking release was comparable for slow and fast compression. CONCLUSIONS: The use of amplification in this study contrasts with previous studies that did not use amplification. The results suggest that when differences in audibility are reduced, participants with hearing loss may be able to take advantage of dips in the noise levels, similar to participants with normal hearing. Although children required a more favorable signal-to-noise ratio than adults for both unmodulated and modulated noise, masking release was not statistically different. However, the ability to detect a difference may have been limited by the small amount of masking release observed. PMID- 26540195 TI - A European Concern? Genetic Structure and Expansion of Golden Jackals (Canis aureus) in Europe and the Caucasus. AB - In the first continent-wide study of the golden jackal (Canis aureus), we characterised its population genetic structure and attempted to identify the origin of European populations. This provided a unique insight into genetic characteristics of a native carnivore population with rapid large-scale expansion. We analysed 15 microsatellite markers and a 406 base-pair fragment of the mitochondrial control region. Bayesian-based and principal components methods were applied to evaluate whether the geographical grouping of samples corresponded with genetic groups. Our analysis revealed low levels of genetic diversity, reflecting the unique history of the golden jackal among Europe's native carnivores. The results suggest ongoing gene flow between south-eastern Europe and the Caucasus, with both contributing to the Baltic population, which appeared only recently. The population from the Peloponnese Peninsula in southern Greece forms a common genetic cluster with samples from south-eastern Europe (DeltaK approach in STRUCTURE, Principal Components Analysis [PCA]), although the results based on BAPS and the estimated likelihood in STRUCTURE indicate that Peloponnesian jackals may represent a distinct population. Moreover, analyses of population structure also suggest either genetic distinctiveness of the island population from Samos near the coast of Asia Minor (BAPS, most STRUCTURE, PCA), or possibly its connection with the Caucasus population (one analysis in STRUCTURE). We speculate from our results that ancient Mediterranean jackal populations have persisted to the present day, and have merged with jackals colonising from Asia. These data also suggest that new populations of the golden jackal may be founded by long-distance dispersal, and thus should not be treated as an invasive alien species, i.e. an organism that is "non-native to an ecosystem, and which may cause economic or environmental harm or adversely affect human health". These insights into the genetic structure and ancestry of Baltic jackals have important implications for management and conservation of jackals in Europe. The golden jackal is listed as an Annex V species in the EU Habitats Directive and as such, considering also the results presented here, should be legally protected in all EU member states. PMID- 26540196 TI - Antagonistic Regulation of Parvalbumin Expression and Mitochondrial Calcium Handling Capacity in Renal Epithelial Cells. AB - Parvalbumin (PV) is a cytosolic Ca2+-binding protein acting as a slow-onset Ca2+ buffer modulating the shape of Ca2+ transients in fast-twitch muscles and a subpopulation of neurons. PV is also expressed in non-excitable cells including distal convoluted tubule (DCT) cells of the kidney, where it might act as an intracellular Ca2+ shuttle facilitating transcellular Ca2+ resorption. In excitable cells, upregulation of mitochondria in "PV-ergic" cells in PV-/- mice appears to be a general hallmark, evidenced in fast-twitch muscles and cerebellar Purkinje cells. Using Gene Chip Arrays and qRT-PCR, we identified differentially expressed genes in the DCT of PV-/- mice. With a focus on genes implicated in mitochondrial Ca2+ transport and membrane potential, uncoupling protein 2 (Ucp2), mitocalcin (Efhd1), mitochondrial calcium uptake 1 (Micu1), mitochondrial calcium uniporter (Mcu), mitochondrial calcium uniporter regulator 1 (Mcur1), cytochrome c oxidase subunit 1 (COX1), and ATP synthase subunit beta (Atp5b) were found to be up-upregulated. At the protein level, COX1 was increased by 31 +/- 7%, while ATP-synthase subunit beta was unchanged. This suggested that these mitochondria were better suited to uphold the electrochemical potential across the mitochondrial membrane, necessary for mitochondrial Ca2+ uptake. Ectopic expression of PV in PV-negative Madin-Darby canine kidney (MDCK) cells decreased COX1 and concomitantly mitochondrial volume, while ATP synthase subunit beta levels remained unaffected. Suppression of PV by shRNA in PV-expressing MDCK cells led subsequently to an increase in COX1 expression. The collapsing of the mitochondrial membrane potential by the uncoupler CCCP occurred at lower concentrations in PV-expressing MDCK cells than in control cells. In support, a reduction of the relative mitochondrial mass was observed in PV-expressing MDCK cells. Deregulation of the cytoplasmic Ca2+ buffer PV in kidney cells was counterbalanced in vivo and in vitro by adjusting the relative mitochondrial volume and modifying the mitochondrial protein composition conceivably to increase their Ca2+-buffering/sequestration capacity. PMID- 26540197 TI - Immunization with a Double-Mutant (R192G/L211A) of the Heat-Labile Enterotoxin of Escherichia coli Offers Partial Protection against Campylobacter jejuni in an Adult Mouse Intestinal Colonization Model. AB - We have previously shown that antibodies to cholera toxin (CT) reacted with the major outer membrane proteins (MOMPs) from Campylobacter jejuni strains on Western blot. Further, oral immunization with CT significantly protected against challenge with C. jejuni in an adult mouse colonization model of infection. CT and the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli are structurally and functionally related. LT and its mutants including the double mutant LT (R192G/L211A) (dmLT), are powerful mucosal adjuvants. Unlike LT which is reactogenic, dmLT has been shown to be safe for human use. In the current study, we determined whether rabbit anti-dmLT antibodies reacted with MOMPs from C. jejuni strains and whether immunization with dmLT would afford protection against C. jejuni. On Western blot, the MOMPs from C. jejuni 48 (Penner serotype O:19), C. jejuni 75 (O:3) and C. jejuni 111 (O:1,44) were probed with rabbit antibodies to dmLT or LT-E112K (a non-toxic LT mutant), which showed a lack of reaction. Adult BALB/c mice were orally immunized with dmLT and orally challenged with C. jejuni 48 or 111. Protection from colonization with the challenge bacteria was studied by enumerating Campylobacter colonies in feces daily for 9 days. Vaccination produced robust serum and stool antibody responses to dmLT and no antibody responses to C. jejuni MOMP. Vaccinated mice showed reduced colonization and excretion of both challenge strains compared to control mice. However, the differences were not statistically significant. The protective efficacy of the dmLT vaccine varied from 9.1% to 54.5%. The lack of cross reaction between the MOMP and dmLT suggests that protection is not mediated by cross-reacting antibodies, but may be due to activation of innate immunity. As dmLT is safe for humans, it could be incorporated into a C. jejuni vaccine to enhance its efficacy. PMID- 26540199 TI - Correction: Occupational Screening for Tuberculosis and the Use of a Borderline Zone for Interpretation of the IGRA in German Healthcare Workers. PMID- 26540198 TI - Thioredoxin-2 Modulates Neuronal Programmed Cell Death in the Embryonic Chick Spinal Cord in Basal and Target-Deprived Conditions. AB - Thioredoxin-2 (Trx2) is a mitochondrial protein using a dithiol active site to reduce protein disulfides. In addition to the cytoprotective function of this enzyme, several studies have highlighted the implication of Trx2 in cellular signaling events. In particular, growing evidence points to such roles of redox enzymes in developmental processes taking place in the central nervous system. Here, we investigate the potential implication of Trx2 in embryonic development of chick spinal cord. To this end, we first studied the distribution of the enzyme in this tissue and report strong expression of Trx2 in chick embryo post mitotic neurons at E4.5 and in motor neurons at E6.5. Using in ovo electroporation, we go on to highlight a cytoprotective effect of Trx2 on the programmed cell death (PCD) of neurons during spinal cord development and in a novel cultured spinal cord explant model. These findings suggest an implication of Trx2 in the modulation of developmental PCD of neurons during embryonic development of the spinal cord, possibly through redox regulation mechanisms. PMID- 26540200 TI - A New Form of Triple-Stranded Helicate Found in Uranyl Complexes of Aliphatic alpha,omega-Dicarboxylates. AB - The reaction of uranyl ions with azelaic or dodecanedioic acids under solvohydrothermal conditions leads to crystallization of anionic dinuclear cage compounds with [M(bipy/phen)3](2+) counterions (M = 3d-block cation), while the smaller suberic acid yields heterometallic metallacycles. Complexes with the longer aliphatic chains are the first triple-stranded helicates reported in actinide chemistry. PMID- 26540201 TI - Zero order and signal processing spectrophotometric techniques applied for resolving interference of metronidazole with ciprofloxacin in their pharmaceutical dosage form. AB - Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of metronidazole as interference. The methods under study are area under the curve, simultaneous equation in addition to smart signal processing techniques of manipulating ratio spectra namely Savitsky-Golay filters and continuous wavelet transform. All the methods were validated according to the ICH guidelines where accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can therefore be used for the routine analysis of ciprofloxacin in quality-control laboratories. PMID- 26540202 TI - Asymmetric H2O-Nucleophilic Ring Opening of D-A Cyclopropanes: Catalyst Serves as a Source of Water. AB - The first catalytic enantioselective ring-opening reaction of donor-acceptor cyclopropanes with water is described. By employing Cy-TOX/Cu(II) as catalyst, the reaction performed very well over a broad range of substrates, leading to the ring-opening products in 70-96% yields with up to 95% ee under mild conditions. The current method provides a new approach to direct access to gamma-substituted GBH derivatives very efficiently. Importantly, Cu(ClO4)2.6H2O proves to serve as both a Lewis acid and a source of water, which affords a fine system to controllably release water as a nucleophile in the asymmetric catalysis. PMID- 26540203 TI - Effect of treatment temperature on the microstructure of asphalt binders: insights on the development of dispersed domains. AB - This paper offers important insights on the development of the microstructure in asphalt binders as a function of the treatment temperature. Different treatment temperatures are useful to understand how dispersed domains form when different driving energies for the mobility of molecular species are provided. Small and flat dispersed domains, with average diameter between 0.02 and 0.70 MUm, were detected on the surface of two binders at room temperature, and these domains were observed to grow with an increase in treatment temperature (up to over 2 MUm). Bee-like structures started to appear after treatment at or above 100 degrees C. Moreover, the effect of the binder thickness on its microstructure at room temperature and at higher treatment temperatures was investigated and is discussed in this paper. At room temperature, the average size of the dispersed domains increased as the binder thickness decreased. A hypothesis that conciliates current theories on the origin and development of dispersed domains is proposed. Small dispersed domains (average diameter around 0.02 MUm) are present in the bulk of the binder, whereas larger domains and bee-like structures develop on the surface, following heat treatment or mechanical disturbance that reduces the film thickness. Molecular mobility and association are the key factors in the development of binder microstructure. PMID- 26540205 TI - Tokophobia, the Fear of Childbirth, and the Decision to Breastfeed. PMID- 26540204 TI - Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons. AB - During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F) that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons. PMID- 26540206 TI - The complete mitochondrial genome of the navel orangeworm Amyelois transitella (Insecta: Lepidoptera: Pyralidae). AB - The complete mitochondrial genome of the navel orangeworm Amyelois transitella (Insecta: Lepidoptera: Pyralidae) was assembled from Illumina sequencing reads (Illumina Inc., San Diego, CA). The genome is a double-stranded circular molecule of 15 205 bp, comprising 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), and one control region. All PCGs are initiated with ATN codons, except for COX1 with the putative CGA initiation codon. Six PCGs (COX1, COX2, CYTB, ND2, ND3, and ND4) harbor an incomplete termination codon T, while all the others are terminated with TAA (ATP6, ATP8, COX3, ND1, ND4, and ND6) or TAG (ND4L). The base composition is highly biased (37.9% A, 12.6% C, 7.8% G, and 41.7% T) with an overall A + T content of 79.6%. Phylogenetic analysis indicated that A. transitella is more phylogenetically related to its confamilial counterparts than to those from the family Crabidae. PMID- 26540207 TI - Rational Phosphorus Application Facilitates the Sustainability of the Wheat/Maize/Soybean Relay Strip Intercropping System. AB - Wheat (Triticum aestivum L.)/maize (Zea mays L.)/soybean (Glycine max L.) relay strip intercropping (W/M/S) system is commonly used by the smallholders in the Southwest of China. However, little known is how to manage phosphorus (P) to enhance P use efficiency of the W/M/S system and to mitigate P leaching that is a major source of pollution. Field experiments were carried out in 2011, 2012, and 2013 to test the impact of five P application rates on yield and P use efficiency of the W/M/S system. The study measured grain yield, shoot P uptake, apparent P recovery efficiency (PRE) and soil P content. A linear-plateau model was used to determine the critical P rate that maximizes gains in the indexes of system productivity. The results show that increase in P application rates aggrandized shoot P uptake and crops yields at threshold rates of 70 and 71.5 kg P ha-1 respectively. With P application rates increasing, the W/M/S system decreased the PRE from 35.9% to 12.3% averaged over the three years. A rational P application rate, 72 kg P ha-1, or an appropriate soil Olsen-P level, 19.1 mg kg-1, drives the W/M/S system to maximize total grain yield while minimizing P surplus, as a result of the PRE up to 28.0%. We conclude that rational P application is an important approach for relay intercropping to produce high yield while mitigating P pollution and the rational P application-based integrated P fertilizer management is vital for sustainable intensification of agriculture in the Southwest of China. PMID- 26540208 TI - White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12 Year Follow-Up. AB - We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression. PMID- 26540209 TI - Fungal biodegradation of anthracene-polluted cork: A comparative study. AB - The efficiency of cork waste in adsorbing aqueous polycyclic aromatic hydrocarbons (PAHs) has been previously reported. Biodegradation of contaminated cork using filamentous fungi could be a good alternative for detoxifying cork to facilitate its final processing. For this purpose, the degradation efficiency of anthracene by three ligninolytic white-rot fungi (Phanerochaete chrysosporium, Irpex lacteus and Pleurotus ostreatus) and three non-ligninolytic fungi which are found in the cork itself (Aspergillus niger, Penicillium simplicissimum and Mucor racemosus) are compared. Anthracene degradation by all fungi was examined in solid-phase cultures after 0, 16, 30 and 61 days. The degradation products of anthracene by P. simplicissimum and I. lacteus were also identified by GC-MS and a metabolic pathway was proposed for P. simplicissimum. Results show that all the fungi tested degraded anthracene. After 61 days of incubation, approximately 86%, 40%, and 38% of the initial concentration of anthracene (i.e., 100 uM) was degraded by P. simplicissimum, P. chrysosporium and I. lacteus, respectively. The rest of the fungi degraded anthracene to a lesser extent (<30%). As a final remark, the results obtained in this study indicate that P. simplicissimum, a non ligninolytic fungi characteristic of cork itself, could be used as an efficient degrader of PAH-contaminated cork. PMID- 26540210 TI - Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups. AB - BACKGROUND: Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up. METHODS: A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes. FINDINGS: After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1-0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl. CONCLUSIONS: The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT00327574. PMID- 26540211 TI - Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates. AB - We report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C14, DMPC) in discoidal "bicelles" (0.156 h(-1)) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 * 10(-3) h(-1)). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C14 DMPC to di-C16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differential scanning calorimetry (DSC), and fluorescence correlation spectroscopy (FCS) are in good agreement. The present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes. PMID- 26540212 TI - Development of antibiotic-loaded silk fibroin/hyaluronic acid polyelectrolyte film coated CoCrMo alloy. AB - Bacteria related infections are still a major problem for the implant materials. Such infections have occurred in nearly 3% of hip and knee replacements resulting in failure of device. There are two main approaches for inhibiting the bacterial adhesion to the surface. These involve bactericidal substances and anti-adhesive coatings. In this study, the efficiency of antibiotic-loaded silk fibroin/hyaluronic acid polyelectrolyte film coated CoCrMo alloy, prepared by means of complex coacervate and layer by layer techniques, was investigated. A medical grade CoCrMo was coated with variable number of silk fibroin/hyaluronic acid up to 14 layers at room temperature. The morphological evolution during and after formation of the crystal structure on the coating layer, the resulting surface roughness, and the corresponding alterations in the coating layer thicknesses were thoroughly studied using various analytical techniques, including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). As a result, only 10 layers of silk fibroin/hyaluronic acid complex coacervate films were found to convey the general characteristics of the mixture of silk I and II, while layer by layer coated samples exhibited the mixture of silk I and II. Moreover, regardless of the preparation method applied, the surface roughness and the coating layer thicknesses were determined to increase with the increasing number of layers. The antibacterial test results suggested that the samples loaded with antibiotic successfully induced a bactericidal resistance against Staphylococcus aureus bacteria. PMID- 26540213 TI - Impact of maternal age on delivery outcomes following spontaneous labour at term. AB - AIM: Pregnancy in women of advancing maternal age is linked to incrementally worsening perinatal outcome. The aim of this study is to assess the impact of maternal age on delivery outcome in women that spontaneously labour at term. METHODS: This was a retrospective study of women that spontaneously labour at term. Women with singletons in spontaneous onset labour beyond 37 weeks of gestation were divided into five maternal age groups: <19 years, 20-24 years, 25 29 years, 30-34 years and >35 years by their age at delivery. The main outcome variables are augmentation of labour, caesarean section, assisted vaginal delivery, and perineal trauma, while admission of the newborn into the neonatal unit within 24 h following delivery was the secondary outcome measure. RESULTS: A total of 30,022 met the inclusion criteria with primiparae and multiparae accounting for 46 and 54%, respectively. Increasing age in primiparae was associated with; augmentation of labour OR 2.05 (95% CI 1.73-2.43), second degree perineal tear 1.35 (1.12-1.61), assisted vaginal delivery 1.92 (1.53-2.41) and caesarean section 4.23 (3.19-5.12). While that for multiparae; augmentation of labour OR 1.93 (1.05-3.52), perineal trauma 2.50 (1.85-3.34), assisted vaginal delivery 4.95 (91.82-13.35) and caesarean section 1.64 (1.13-2.38). The secondary outcome measure did not reach statistical significance. CONCLUSION: Increasing maternal age is an independent risk factor for operative delivery, and perineal trauma. However, maternal age has no significant effect on admission of infants into the NICU during the first 24 h following delivery. PMID- 26540214 TI - Fertility treatment and dichorionic discordant twins - are they related? AB - OBJECTIVE: This prospective cohort study evaluated the relationship between fertility treatments and the prevalence and outcomes of dichorionic discordant twins. This issue has gained importance due to twin gestations resulting from fertility treatments. STUDY DESIGN: Mothers of dichorionic twin pregnancies achieved in a single fertility clinic by assisted reproduction techniques, who had completed the first trimester of the pregnancy, were prospectively enrolled. Pregnancies with major fetal anomalies were excluded. Data regarding concordant and discordant twins based on the fertility treatments given to achieve the pregnancies were analyzed to determine the prevalence of discordance and pregnancy outcomes. RESULTS: A total of 571 dichorionic twin pregnancies were available for evaluation. Fertility treatments modalities, sperm quality and implantation of cultured and thawed embryos did not influence the rate and severity of discordant twins. Increased hospitalization rates were found among discordant (n=108) compared to concordant (n=463) twins (47.2% vs. 31.3%, P<0.0001) and higher rates of betamethasone treatment (65.7% vs. 28.9%, P<0.0001). Secondary analysis of discordant pregnancies with a growth restricted twin, revealed the same results. We found no association between various fertility treatments and twin discordance. CONCLUSIONS: Our data suggest that fertility treatments do not play a major role in the pervasiveness and outcome of discordant twin pregnancies. PMID- 26540215 TI - Intertwin estimated fetal weight or crown rump length discordance and adverse perinatal outcome. AB - AIM: In the current review study, we present recent data regarding the importance of intertwin estimated fetal weight (EFW) and crown rump length (CRL) discordance for the prediction of adverse perinatal outcome both in monochorionic and in dichorionic diamniotic gestations. RESULTS: Twins with significant weight disparity are associated with higher rates of perinatal morbidity and mortality, regardless of gestational age at delivery. However, there is no agreement regarding as to the cut off value above which the perinatal outcome is unfavorably affected and the threshold range from 10 to 30%. On the other hand, CRL discrepancy has proved to be a weak predictor of adverse outcomes, such as fetal or neonatal death in fetuses without chromosomal and structural abnormalities. In clinical practice, decisions about obstetric surveillance of discordant twin gestations, frequency of fetal sonographic monitoring and time of delivery are usually based on amniotic fluid volume and Doppler assessments on a weekly basis. CONCLUSION: Significant EFW discordance leads to adverse perinatal outcome, although the cut-off value has not yet been estimated. CRL discrepancy is not correlated well with adverse perinatal outcome. However, increased monitoring of women with EFW and CRL discrepancy is suggested. PMID- 26540216 TI - Maternal risk: assessment and management. PMID- 26540217 TI - A longitudinal study of brainstem auditory response from birth to late term in late preterm babies and abnormal findings in high-risk babies. AB - OBJECTIVES: The objective of this study was to examine brainstem auditory function in late preterm babies from birth to late term and detect abnormality in high-risk babies. METHODS: A total of 125 babies born at 33-36 weeks' gestations were studied by longitudinally recording brainstem auditory evoked response from birth to postconceptional age (PCA) 42 weeks. The data were compared between 88 babies who had various perinatal problems (high-risk group) and 37 babies who had no major perinatal problems (healthy group). RESULTS: As PCA increased from 33 to 42 weeks, all wave latencies and I-V interpeak interval in brainstem auditory evoked response were decreased, while all wave amplitudes were increased in these babies. At PCA 33-34 weeks, wave III and V latencies and I-V interval in the high risk late preterm babies were significantly longer than those in the healthy late preterm babies (P<0.05-0.01). At PCA 35-36 weeks, both V latency and I-V interval were significantly longer than those in the healthy babies (P<0.05 and 0.01). During the term period (PCA 37-42 weeks), these differences became smaller with increasing age. The wave V latency and I-V interval in the high-risk babies were significantly longer than those in the healthy babies at PCA 37-38 and 39-40 weeks (all P<0.05), though not significantly at PCA 41-42 weeks. The amplitudes of waves I, III, and V all tended to be smaller than those in the healthy babies. CONCLUSIONS: During early life, brainstem auditory function is abnormal in high risk late preterm babies. The abnormality is most significant at early preterm, improves with increasing age and approaches normal at late term. PMID- 26540218 TI - Carotid intima media thickness in obese children: is there an association with hyperlipidemia? AB - BACKGROUND: We aimed to evaluate the association between hyperlipidemia and carotid intima media thickness in obese children, compared to non-obese ones. METHODS: Two hundred (110 girls, 90 boys) children aged between 6 and 15 years participated in this study. The obese group included 53 girls, 47 boys whose body mass indices (BMI) above 95th percentile, the control group included 57 girls, 43 boys who had normal weight. Fasting total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were measured. Carotid intima media thickness (cIMT) was performed with neck ultrasound. RESULTS: The median thickness of right, left and mean carotis intima media were statistically higher in the study group, compared to the control group. The mean cholesterol, triglyceride, HDL-C, LDL-C levels of the study group were statistically higher, compared to the control group. There was no relationship between BMI and left carotis intima media thickness, but there was statistically significant relationship between BMI and right, mean cIMTs in the study group. There was no correlation between serum lipid levels and cIMTs in the study group. The mean atherogenic index of the study group was statistically higher, compared to the control group. There was no statistical correlation between atherogenic index and cIMTs in both of the groups. CONCLUSIONS: We observed that obese children had higher carotis intima media thicknesses. Carotis intima media thickness related to obesity can play an important role in future pre-atherosclerotic changes. Large population based studies are required to confirm this associaton. PMID- 26540219 TI - The functional role of all postsynaptic potentials examined from a first-person frame of reference. AB - When assigning a central role to the neuronal firing, a large number of incoming postsynaptic potentials not utilized during both supra- and subthreshold neuronal activations are not given any functional significance. Local synaptic potentials at the apical dendrites get attenuated as they arrive at the soma to nearly a twentieth of what a synapse proximal to the soma produces. Conservation of these functions necessitates searching for their functional roles. Potentials induced at the postsynapses of neurons of all the neuronal orders activated by sensory inputs carry small bits of sensory information. The activation of these postsynapses by any means other than the activation from their corresponding presynaptic terminals, that also contribute to oscillating potentials, induce the semblance of the arrival of activity from their presynaptic terminals. This is a candidate mechanism for inducing the first-person internal sensory elements of various higher brain functions as a systems property. They also contribute to the firing of subthreshold-activated neurons, including motor neurons. Operational mechanism of inter-postsynaptic functional LINKs can provide necessary structural requirements for these functions. The functional independence of the distal dendritic compartment and recent evidence for in vivo dendritic spikes indicate their independent role in the formation of internal sensory elements. In these contexts, a neuronal soma is flanked by a large number of quasi-functional internal sensory processing units operated using very little energy, even when a neuron is not firing. A large number of possible combinations of internal sensory units explains the corresponding number of specific memory retrievals by the system in response to various cue stimuli. PMID- 26540220 TI - The role of non-receptor protein tyrosine kinases in the excitotoxicity induced by the overactivation of NMDA receptors. AB - Protein tyrosine phosphorylation is one of the primary modes of regulation of N methyl-d-aspartate (NMDA) receptors. The non-receptor tyrosine kinases are one of the two types of protein tyrosine kinases that are involved in this process. The overactivation of NMDA receptors is a primary reason for neuron death following cerebral ischemia. Many studies have illustrated the important role of non receptor tyrosine kinases in ischemia insults. This review introduces the roles of Src, Fyn, focal adhesion kinase, and proline-rich tyrosine kinase 2 in the excitotoxicity induced by the overactivation of NMDA receptors following cerebral ischemia. PMID- 26540222 TI - 1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing. AB - Poppy seeds are widely used in household and commercial confectionery. The aim of this study was to demonstrate the application of metabolic profiling for industrial monitoring of the molecular changes which occur during minced poppy seed rancidity and brewing processes performed on raw seeds. Both forms of poppy seeds were obtained from a confectionery company. Proton nuclear magnetic resonance (1H NMR) was applied as the analytical method of choice together with multivariate statistical data analysis. Metabolic fingerprinting was applied as a bioprocess control tool to monitor rancidity with the trajectory of change and brewing progressions. Low molecular weight compounds were found to be statistically significant biomarkers of these bioprocesses. Changes in concentrations of chemical compounds were explained relative to the biochemical processes and external conditions. The obtained results provide valuable and comprehensive information to gain a better understanding of the biology of rancidity and brewing processes, while demonstrating the potential for applying NMR spectroscopy combined with multivariate data analysis tools for quality control in food industries involved in the processing of oilseeds. This precious and versatile information gives a better understanding of the biology of these processes. PMID- 26540221 TI - Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl cannabidiol - studies in BV-2 microglia and encephalitogenic T cells. AB - BACKGROUND: Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells. METHODS: BV-2 cells were pretreated with DMH-CBD, followed by stimulation with the endotoxin lipopolysaccharide (LPS). The expression levels of selected genes involved in stress regulation and inflammation were determined by quantitative real-time PCR. In addition, MOG35-55 reactive T cells (TMOG) were cultured with antigen-presenting cells in the presence of DMH-CBD and MOG35-55 peptide, and cell proliferation was determined by measuring [3H]thymidine incorporation. RESULTS: DMH-CBD treatment downregulated in a dose-dependent manner the mRNA expression of LPS-upregulated pro-inflammatory genes (Il1b, Il6, and Tnf) in BV-2 microglial cells. The expression of these genes was also downregulated by DMH-CBD in unstimulated cells. In parallel, DMH-CBD upregulated the expression of genes related to oxidative stress and glutathione homeostasis such as Trb3, Slc7a11/xCT, Hmox1, Atf4, Chop, and p8 in both stimulated and unstimulated microglial cells. In addition, DMH-CBD dose-dependently inhibited MOG35-55-induced TMOG proliferation. CONCLUSIONS: The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells. PMID- 26540223 TI - In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer. AB - Cell competition is identified as a crucial phenomenon for cancer and organ development. There is a possibility that microRNAs (miRNAs) may play an important role in the regulation of expression of genes involved in cell competition. In silico screening of miRNAs is an effort to abridge, economize and expedite the experimental approaches to identification of potential miRNAs involved in cell competition, as no study has reported involvement of miRNAs in cell competition to date. In this study, we used multiple screening steps as follows: (i) selection of cell competition related genes of Drosophila through a literature survey; (ii) homology study of selected cell competition related genes; (iii) identification of miRNAs that target conserved cell competition-related genes through prediction tools; (iv) sequence conservation analysis of identified miRNAs with human genome; (v) identification of conserved cell competition miRNAs using their expression profiles and exploration of roles of their homologous human miRNAs. This study led to the identification of nine potential cell competition miRNAs in the Drosophila genome. Importantly, eighteen human homologs of these nine potential Drosophila miRNAs are well reported for their involvement in different types of cancers. This confirms their probable involvement in cell competition as well, because cell competition is well justified for its involvement in cancer initiation and maintenance. PMID- 26540224 TI - Homology arms of targeting vectors for gene insertions and CRISPR/Cas9 technology: size does not matter; quality control of targeted clones does. AB - Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) technology has brought rapid progress in mammalian genome editing (adding, disrupting or changing the sequence of specific sites) by increasing the frequency of targeted events. However, gene knock-in of DNA cassettes by homologous recombination still remains difficult due to the construction of targeting vectors possessing large homology arms (from 2 up to 5 kb). Here, we demonstrate that in mouse embryonic stem cells the combination of CRISPR/Cas9 technology and targeting vectors with short homology arms (~ 0.3 kb) provides sufficient specificity for insertion of fluorescent reporter cassettes into endogenous genes with similar efficiency as those with large conventional vectors. Importantly, we emphasize the necessity of thorough quality control of recombinant clones by combination of the PCR method, Southern hybridization assay and sequencing to exclude undesired mutations. In conclusion, our approach facilitates programmed integration of exogenous DNA sequences at a target locus and thus could serve as a basis for more sophisticated genome engineering approaches, such as generation of reporters and conditional knock-out alleles. PMID- 26540225 TI - Death domain associated protein (Daxx), a multi-functional protein. AB - Death domain associated protein (Daxx), a multi-functional protein, plays an important role in transcriptional regulation, cell apoptosis, carcinogenesis, anti-virus infection and so on. However, its regulatory mechanisms for both cell survival and apoptosis remain largely obscure. Our review of recent studies shows that Daxx has many interesting functional dualities and can provide a reference for further research on Daxx. PMID- 26540226 TI - Corrigendum to: potential importance of Maackia amurensis agglutinin in non-small cell lung cancer. PMID- 26540227 TI - Total error vs. measurement uncertainty: revolution or evolution? AB - The first strategic EFLM conference "Defining analytical performance goals, 15 years after the Stockholm Conference" was held in the autumn of 2014 in Milan. It maintained the Stockholm 1999 hierarchy of performance goals but rearranged them and established five task and finish groups to work on topics related to analytical performance goals including one on the "total error" theory. Jim Westgard recently wrote a comprehensive overview of performance goals and of the total error theory critical of the results and intentions of the Milan 2014 conference. The "total error" theory originated by Jim Westgard and co-workers has a dominating influence on the theory and practice of clinical chemistry but is not accepted in other fields of metrology. The generally accepted uncertainty theory, however, suffers from complex mathematics and conceived impracticability in clinical chemistry. The pros and cons of the total error theory need to be debated, making way for methods that can incorporate all relevant causes of uncertainty when making medical diagnoses and monitoring treatment effects. This development should preferably proceed not as a revolution but as an evolution. PMID- 26540228 TI - Cumulative effect of short-term and long-term meditation practice in men and women on psychophysiological parameters of electrophotonic imaging: a cross sectional study. AB - BACKGROUND: Anapanasati is one of the meditation techniques discussed in Buddhism. In this meditation, one focuses one's attention on bodily sensations caused by incoming and outgoing breath. This study aims to track the cumulative effect of long-term meditators (LTM) and short-term meditators (STM) using electrophotonic imaging (EPI). METHODS: To execute the current study, 432 subjects (264 men and 168 women with mean age of 34.36+/-6.83) were recruited from two meditation centers. LTM had practiced for more than 60 months (mean of months 111+/-47.20, hoursperday 1.71+/-1.20). STM had practiced meditation from 6 months to less than 60 months (mean of months 37.17+/-19.44, hoursperday 2.14+/ 4.99). A cross-sectional research design was applied and data was collected using EPI. Scatter plot and Fisher discriminant model were also used for statistical presentation of values and interdependency of variables with length of practice between groups. RESULTS: In both LTM and STM, lower values of stress (activation coefficient) were found in woman meditators as compared to men. In both groups, highly significant gender-related differences were observed in integral area parameter, which measures the overall health of an individual. Integral entropy (index of disorderliness of subtle energy in the body) was fluctuating in both groups in both directions for both genders. It was increasing in LTM group and decreasing in STM group with increasing length of practice. CONCLUSIONS: Women of LTM and STM demonstrated lesser stress than men. Both groups showed cumulative health-related improvement. Moreover, in gender-related analysis woman meditators exhibited more positive improvement in EPI parameters than men. PMID- 26540229 TI - Angular Dependence of Exchange Bias and Magnetization Reversal Controlled by Electric-Field-Induced Competing Anisotropies. AB - The combination of exchange-biased systems and ferroelectric materials offers a simple and effective way to investigate the angular dependence of exchange bias using one sample with electric-field-induced competing anisotropies. A reversible electric-field-controlled magnetization reversal at zero magnetic field is also realized through optimizing the anisotropy configuration, holding promising applications for ultralow power magnetoelectric devices. PMID- 26540230 TI - Genomics of Cancer and a New Era for Cancer Prevention. AB - A primary justification for dedicating substantial amounts of research funding to large-scale cancer genomics projects of both somatic and germline DNA is that the biological insights will lead to new treatment targets and strategies for cancer therapy. While it is too early to judge the success of these projects in terms of clinical breakthroughs, an alternative rationale is that new genomics techniques can be used to reduce the overall burden of cancer by prevention of new cases occurring and also by detecting them earlier. In particular, it is now becoming apparent that studying the genomic profile of tumors can help to identify new carcinogens and may subsequently result in implementing strategies that limit exposure. In parallel, it may be feasible to utilize genomic biomarkers to identify cancers at an earlier and more treatable stage using screening or other early detection approaches based on prediagnostic biospecimens. While the potential for these techniques is large, their successful outcome will depend on international collaboration and planning similar to that of recent sequencing initiatives. PMID- 26540231 TI - Many children aged two to five years have a persistent presence of respiratory viruses in their nasopharynx. PMID- 26540232 TI - Cognitive impairment and spontaneous epilepsy in rats with malformations of cortical development. AB - PURPOSE: To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs. METHODS: An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining. RESULTS: The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups. CONCLUSION: The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X irradiation. PMID- 26540233 TI - Facility Death Review of Maternal and Neonatal Deaths in Bangladesh. AB - OBJECTIVES: To explore the experiences, acceptance, and effects of conducting facility death review (FDR) of maternal and neonatal deaths and stillbirths at or below the district level in Bangladesh. METHODS: This was a qualitative study with healthcare providers involved in FDRs. Two districts were studied: Thakurgaon district (a pilot district) and Jamalpur district (randomly selected from three follow-on study districts). Data were collected between January and November 2011. Data were collected from focus group discussions, in-depth interviews, and document review. Hospital administrators, obstetrics and gynecology consultants, and pediatric consultants and nurses employed in the same departments of the respective facilities participated in the study. Content and thematic analyses were performed. RESULTS: FDR for maternal and neonatal deaths and stillbirths can be performed in upazila health complexes at sub-district and district hospital levels. Senior staff nurses took responsibility for notifying each death and conducting death reviews with the support of doctors. Doctors reviewed the FDRs to assign causes of death. Review meetings with doctors, nurses, and health managers at the upazila and district levels supported the preparation of remedial action plans based on FDR findings, and interventions were planned accordingly. There were excellent examples of improved quality of care at facilities as a result of FDR. FDR also identified gaps and challenges to overcome in the near future to improve maternal and newborn health. DISCUSSION: FDR of maternal and neonatal deaths is feasible in district and upazila health facilities. FDR not only identifies the medical causes of a maternal or neonatal death but also explores remediable gaps and challenges in the facility. FDR creates an enabled environment in the facility to explore medical causes of deaths, including the gaps and challenges that influence mortality. FDRs mobilize health managers at upazila and district levels to forward plan and improve healthcare delivery. PMID- 26540234 TI - Bronchial Smooth Muscle Remodeling in Nonsevere Asthma. AB - RATIONALE: Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from nonsevere asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in individuals with severe asthma. However, BSM remodeling and mitochondrial biogenesis have not been examined in nonsevere asthma. OBJECTIVES: We aimed to assess whether an increase in BSM mass was also implicated in nonsevere asthma and its relationship with mitochondria and clinical outcomes. METHODS: We enrolled 34 never-smoker subjects with nonsevere asthma. In addition, we recruited 56 subjects with nonsevere asthma and 19 subjects with severe asthma as comparative groups (COBRA cohort [Cohorte Obstruction Bronchique et Asthme; Bronchial Obstruction and Asthma Cohort; sponsored by the French National Institute of Health and Medical Research, INSERM]). A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide measurement, and blood collection. Bronchial biopsy specimens were processed for immunohistochemistry and electron microscopy analysis. After BSM remodeling assessment, subjects were monitored over a 12-month period. MEASUREMENTS AND MAIN RESULTS: We identified characteristic features of remodeling (BSM area >26.6%) and increased mitochondrial number within BSM in a subgroup of subjects with nonsevere asthma. The number of BSM mitochondria was positively correlated with BSM area (r = 0.78; P < 0.001). Follow-up analysis showed that subjects with asthma with high BSM had worse asthma control and a higher rate of exacerbations per year compared with subjects with low BSM. CONCLUSIONS: This study reveals that BSM remodeling and mitochondrial biogenesis may play a critical role in the natural history of nonsevere asthma (Mitasthme study). Clinical trial registered with www.clinicaltrials.gov (NCT00808730). PMID- 26540235 TI - Electrospinning as a powerful technique for biomedical applications: a critically selected survey. AB - Nowadays, electrospinning has become one of the most versatile, easy, and cost effective techniques to engineer advanced materials used for many applications, especially in the biomedical and environmental areas. Like the numerous patents around the world, the increasing number of papers witnesses the huge potential of this simple process, and many companies have been emerged during the last years to exploit its innumerable applications. This article presents a critically selected overview of polymers that can be used to produce nanofibers, along with the biomedical applications of the resulting electrospun scaffolds. We have focused on about seven natural and synthetic polymers, but many more can be found in the literature, either as their pristine state or as composites with ceramics, metals, and other polymers. The description of some strategies for nanofiber production, and the characterization used to evaluate their optimization, has been discussed. Finally, several polymers have been recognized as highlights for future work. PMID- 26540236 TI - Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013. AB - Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05) and massive O- and N glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines. PMID- 26540237 TI - Intra and Inter-Spore Variability in Rhizophagus irregularis AOX Gene. AB - Arbuscular mycorrhizal fungi (AMF) are root-inhabiting fungi that form mutualistic symbioses with their host plants. AMF symbiosis improves nutrient uptake and buffers the plant against a diversity of stresses. Rhizophagus irregularis is one of the most widespread AMF species in the world, and its application in agricultural systems for yield improvement has increased over the last years. Still, from the inoculum production perspective, a lack of consistency of inoculum quality is referred to, which partially may be due to a high genetic variability of the fungus. The alternative oxidase (AOX) is an enzyme of the alternative respiratory chain already described in different taxa, including various fungi, which decreases the damage caused by oxidative stress. Nevertheless, virtually nothing is known on the involvement of AMF AOX on symbiosis establishment, as well on the existence of AOX variability that could affect AMF effectiveness and consequently plant performance. Here, we report the isolation and characterisation of the AOX gene of R. irregularis (RiAOX), and show that it is highly expressed during early phases of the symbiosis with plant roots. Phylogenetic analysis clustered RiAOX sequence with ancient fungi, and multiple sequence alignment revealed the lack of several regulatory motifs which are present in plant AOX. The analysis of RiAOX polymorphisms in single spores of three different isolates showed a reduced variability in one spore relatively to a group of spores. A high number of polymorphisms occurred in introns; nevertheless, some putative amino acid changes resulting from non-synonymous variants were found, offering a basis for selective pressure to occur within the populations. Given the AOX relatedness with stress responses, differences in gene variants amongst R. irregularis isolates are likely to be related with its origin and environmental constraints and might have a potential impact on inoculum production. PMID- 26540238 TI - Challenges in Patient Recruitment, Implementation, and Fidelity in a Mobile Telehealth Study. AB - INTRODUCTION: Mobile telehealth (MTH) evaluations in diabetes have been conducted, but few report details and issues related to recruitment, implementation (intervention delivery), fidelity, and context. These have important implications on the interpretation of the findings and effectiveness of the intervention. This article reports these data from an MTH study and describes the challenges experienced in running an intervention such as this in an active clinical environment. MATERIALS AND METHODS: We conducted a mixed-methods MTH study that included a 9-month randomized controlled trial in people with poorly controlled diabetes. Detailed recruitment data were recorded during the study. Data on contacts between MTH participants and the MTH team were collected and used to report on intervention delivery and fidelity. Meeting and field notes, as well as communications between research team members during the study, were used to report on the contextual factors that affected recruitment, implementation, and fidelity. RESULTS: The recruited sample size represented 6% of the total clinic population (n = 1,360) and 10.7% of the number of potentially eligible people at the clinic (n = 802) identified at the beginning of the study. Contextual factors related to patients, healthcare providers, the institution, or the recruitment protocol contributed to influence access to study participants and the number of participants randomized (n = 81). Technical and device-related aspects of the MTH intervention were delivered successfully, but the expected education and clinical feedback by the MTH nurse were not delivered according to the protocol. Although 92.5% of introductory calls were made by the MTH nurses, only 13.3% of expected educational calls were performed. Changes to the MTH nursing staff affected intervention participants differently and contributed to the low fidelity of intervention delivery. CONCLUSIONS: The current article presents data on the influence of contextual factors on the conduct of this MTH study and underlines the need for these processes to be assessed and reported adequately in future MTH research. PMID- 26540240 TI - The natural history of small bowel angiodysplasia. AB - BACKGROUND: Small bowel angiodysplasias (SBA) account for 50% of obscure gastrointestinal bleeding. Lesions bleed recurrently and current treatments are relatively ineffective at reducing re-bleeding. Little is known about the natural history of SBA which is needed to guide treatment decisions and counsel patients on prognosis. AIM: The aim of this study is to describe the natural history of a cohort of patients with SBA. METHODS: Patients with SBA were identified retrospectively and clinical and outcome information were collected. Logistic regression analysis was performed to identify factors associated with re bleeding. RESULTS: SBAs were found in 86 patients of which 54% (n = 47) were female, and the average age was 71.6 years. The majority (69%) had multiple lesions, mean of 2.76/patient, and 65% were located in the jejunum. Follow-up was available in 65% (n = 56). There was a significant increase in haemoglobin level from 10.05g/dL to 11.94g/dL, p < 0.001 after mean follow up of 31.9 (6-62) months. Re-bleeding events occurred in 80% (n = 45), with an average of 2.91/person. The mean interval between diagnosis and the first re-bleeding event was 10.7 months. Of the group overall, 70% (n = 40) required transfusions during follow up, and 67% required hospitalisation due to re-bleeding. About 50% received a directed treatment, including argon plasma coagulation, somatostatin analogues, or surgical resection. A total of 3.5% (n = 2) died as a direct consequence of bleeding from SBAs. Multiple lesions (p = 0.048) and valvular heart disease (p = 0.034) were predictive of re-bleeding. CONCLUSION: Our results show the significant impact of SBA on patients' morbidity, with high rates of re bleeding, persistent anaemia and a mortality rate of 3.5%, despite the use of currently available medical and endoscopic therapies. PMID- 26540239 TI - Resting-State fMRI Functional Connectivity Is Associated with Sleepiness, Imagery, and Discontinuity of Mind. AB - Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to investigate the functional architecture of the healthy human brain and how it is affected by learning, lifelong development, brain disorders or pharmacological intervention. Non-sensory experiences are prevalent during rest and must arise from ongoing brain activity, yet little is known about this relationship. Here, we used two runs of rs-fMRI both immediately followed by the Amsterdam Resting State Questionnaire (ARSQ) to investigate the relationship between functional connectivity within ten large-scale functional brain networks and ten dimensions of thoughts and feelings experienced during the scan in 106 healthy participants. We identified 11 positive associations between brain-network functional connectivity and ARSQ dimensions. 'Sleepiness' exhibited significant associations with functional connectivity within Visual, Sensorimotor and Default Mode networks. Similar associations were observed for 'Visual Thought' and 'Discontinuity of Mind', which may relate to variation in imagery and thought control mediated by arousal fluctuations. Our findings show that self-reports of thoughts and feelings experienced during a rs-fMRI scan help understand the functional significance of variations in functional connectivity, which should be of special relevance to clinical studies. PMID- 26540241 TI - Bisphosphonate-Induced Orbital Inflammation: A Case Series and Review. AB - INTRODUCTION: To present a series of patients with bisphosphonate induced orbital inflammation, and to review the clinical presentation, radiological features, treatment options and outcomes. METHODS: We present a multicentre, retrospective case series review of patients with a clinico-radiological diagnosis of bisphosphonate induced orbital inflammation and review all the reported cases of this complication in the literature. RESULTS: Four new patients with bisphosphonate induced orbital inflammation were added to the 25 cases in the literature. Intravenous zoledronate was the commonest precipitant (22/29, 75.9%) and inflammation occurred 1-28 (mean 3) days post-infusion. Orbital imaging identified orbital inflammation in 22/29 cases and extra-ocular muscle enlargement in 8/29. Five patients presented with reduced vision of which one - with anterior ischaemic optic neuropathy - did not resolve. The vision resolved in all except one patient, with most requiring steroid treatment. CONCLUSIONS: Bisphosphonates have a pro-inflammatory effect, which can precipitate orbital inflammation. This rare, but potentially serious complication of bisphosphonate treatment should be considered by clinicians using bisphosphonate treatment and by ophthalmologists seeing patients with orbital inflammatory disease. PMID- 26540242 TI - Intensity of delivery room resuscitation and neonatal outcomes in infants born at 33 to 36 weeks' gestation. AB - OBJECTIVE: Examine the relationship between delivery room resuscitation intensity and mortality, morbidities and resource use in late preterm infants. STUDY DESIGN: Retrospective cohort study of inborn infants born at 33 to 36 weeks' gestation and admitted to Canadian neonatal intensive care units during 2010 to 2013. The 13 619 infants were grouped according to delivery room resuscitation intensity: no or minimal resuscitation (64.5%); continuous positive airway pressure (10.2%); bag-mask ventilation (21.7%); endotracheal intubation (3.1%); and cardiopulmonary resuscitation (CPR) (0.6%). RESULTS: Overall mortality, early mortality, respiratory distress, pneumothorax, late-onset sepsis and resource use increased with higher intensity resuscitation. Compared with no or minimal resuscitation, intubation and CPR were associated with increased odds of mortality (adjusted odds ratio (95% confidence interval): 50 (20 to 125) and 180 (63 to 518), respectively). CONCLUSIONS: Intubation or higher intensity delivery room resuscitation is associated with increased mortality, morbidities and resource use in late preterm infants. Extra intensive care is required for such infants, especially during the first week of life. PMID- 26540243 TI - Delivery modes and pregnancy outcomes of low birth weight infants in China. AB - OBJECTIVE: To investigate and analyze the perinatal outcomes of low birth weight (LBW) infants, thereby selecting the appropriate mode and suitable time of delivery to improve the adverse pregnancy outcomes. STUDY DESIGN: A retrospective analysis of 112,441 deliveries (from 39 hospitals of different levels in 14 provinces and autonomous regions in China throughout 2011) were performed in this study to further evaluate the modes of delivery and pregnancy outcomes of LBW infants. RESULTS: The rate of cesarean section, stillbirth, neonatal asphyxia and mortality of LBW were significantly higher than those of normal birth weight (NBW) infants (odds ratio, 1.24, 56.56, 57.27 and 10.40 times higher, respectively). Stratified analysis showed that adverse events were reduced with the increase in gestational weeks, especially at 34 to 36(+6) weeks. However, LBW infants still had higher risks of adverse events as compared with NBW infants. In particular, full-term LBW babies had a 23.81- and 26.06-fold higher risk of stillbirth and neonatal death as compared with term babies with NBW. In addition, the cesarean delivery rate was 1.24-fold higher for LBW babies than for NBW babies. With an increase in gestational age in LBW infants, the rate of cesarean section was also increased. The rates of stillbirth and neonatal mortality of full-term LBW infants who were delivered via cesarean section (0.5% and 1.0%, respectively) were significantly lower than in the vaginal-delivery group (5.2% and 6.9%, respectively). CONCLUSION: LBW is one of the causes of perinatal death and other adverse pregnancy outcomes and increases the rate of cesarean section. Individualized analysis according to gestational age and intrauterine fetal condition should be performed to extend the gestational age to at least 34 weeks before delivery, cesarean section is a relatively safe mode of delivery, but cannot completely eliminate complications. The key to improving mother and child outcomes is to strengthen pregnancy care and reduce low birth weight infants and premature birth. LBW is one of the causes of adverse pregnancy outcomes in both premature and full-term infants and increases the rate of cesarean section. Individualized analysis of the mode of delivery should be performed to extend the gestational age to 34 weeks and so improve the survival rate. PMID- 26540244 TI - Failed endotracheal intubation and adverse outcomes among extremely low birth weight infants. AB - OBJECTIVE: To quantify the importance of successful endotracheal intubation on the first attempt among extremely low birth weight (ELBW) infants who require resuscitation after delivery. STUDY DESIGN: A retrospective chart review was conducted for all ELBW infants ?1000 g born between January 2007 and May 2014 at a level IV neonatal intensive care unit. Infants were included if intubation was attempted during the first 5 min of life or if intubation was attempted during the first 10 min of life with heart rate <100. The primary outcome was death or neurodevelopmental impairment. The association between successful intubation on the first attempt and the primary outcome was assessed using multivariable logistic regression with adjustment for birth weight, gestational age, gender and antenatal steroids. RESULTS: The study sample included 88 ELBW infants. Forty percent were intubated on the first attempt and 60% required multiple intubation attempts. Death or neurodevelopmental impairment occurred in 29% of infants intubated on the first attempt, compared with 53% of infants that required multiple attempts, adjusted odds ratio 0.4 (95% confidence interval 0.1 to 1.0), P<0.05. CONCLUSION: Successful intubation on the first attempt is associated with improved neurodevelopmental outcomes among ELBW infants. This study confirms the importance of rapid establishment of a stable airway in ELBW infants requiring resuscitation after birth and has implications for personnel selection and role assignment in the delivery room. PMID- 26540245 TI - Milk production after preterm, late preterm and term delivery; effects of different breast pump suction patterns. AB - OBJECTIVE: This study aimed to compare the effectiveness of two different breast pump suction patterns (BPSP) during the initiation of lactation in mothers of term, late preterm and preterm infants. METHODS: Breast pump-dependent mothers (n=130) of term (n=19), late preterm (n=44) and preterm (n=67) infants were assigned to either a standard or irregular-BPSP after birth until the onset of secretory activation. Both groups used the same standard maintenance BPSP thereafter. Time to secretory activation, time to full milk production and daily milk output were compared between the standard and I-BPSP groups, and between the term, late preterm and preterm groups. RESULTS: Mothers using the irregular-BPSP demonstrated significantly greater daily milk output and established secretory activation significantly earlier. This effect was observed in mothers of term, late preterm and preterm infants. CONCLUSION: The irregular-BPSP mimicking sucking of healthy newborns is more effective at achieving secretory activation and an earlier adequate milk supply than the standard-BPSP. The irregular-BPSP can be used successfully for mothers of preterm up to term infants who are breast pump dependent during the establishment of lactation. PMID- 26540246 TI - Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age. AB - OBJECTIVE: Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants. STUDY DESIGN: A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression. RESULTS: Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P?0.001), shorter (57.9 vs 60.9 cm, P?0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P?0.05) and were leaner (percent body fat 15.0 vs 23.8, P?0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors. CONCLUSIONS: Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development. PMID- 26540247 TI - The impact of inadequate gestational weight gain in obese diabetic women. AB - OBJECTIVE: To determine the effect of inadequate gestational weight gain (GWG) on neonatal birth weight in diabetic obese women. STUDY DESIGN: Retrospective cohort study of women with an initial body mass index (BMI) ?30 kg m(-2) and gestational or type 2 diabetes was conducted. GWG was stratified: inadequate (<11 lbs), adequate (11 to 20 lbs) or excessive (>20 lbs). The primary outcome was birth weight. Secondary outcomes included hypertensive disorders, gestational age at delivery, mode of delivery and Apgar scores. RESULT: A total of 211 obese diabetic women were identified. Of those, 37% had inadequate GWG, 25% had adequate GWG and 38% had excessive GWG. Women with inadequate GWG had lower mean birth weights (P=0.048), as well as lower rates of cesarean delivery (P=0.017) and lower rates of pregnancy-related hypertensive disorders (P=0.026) compared with those with adequate and excessive GWG. CONCLUSION: Inadequate GWG was associated lower mean birth weights, lower rates of cesarean delivery and lower rates of pregnancy-related hypertensive disorders. PMID- 26540248 TI - Effect of community-based newborn care on cause-specific neonatal mortality in Sylhet district, Bangladesh: findings of a cluster-randomized controlled trial. AB - OBJECTIVES: Community-based maternal and newborn intervention packages have been shown to reduce neonatal mortality in resource-constrained settings. This analysis uses data from a large community-based cluster-randomized trial to assess the impact of a community-based package on cause-specific neonatal mortality and draws programmatic and policy implications. In addition, the study shows that cause-specific mortality estimates vary substantially based on the hierarchy used in assigning cause of death, which also has important implications for program planning. Therefore, understanding the methods of assigning causes of deaths is important, as is the development of new methodologies that account for multiple causes of death. The objective of this study was to estimate the effect of two service delivery strategies (home care and community care) for a community based package of maternal and neonatal health interventions on cause-specific neonatal mortality rates in a rural district of Bangladesh. STUDY DESIGN: Within the general community of the Sylhet district in rural northeast Bangladesh. Pregnancy histories were collected from a sample of women in the study area during the year preceding the study (2002) and from all women who reported a pregnancy outcome during the intervention in years 2004 to 2005. All families that reported a neonatal death during these time periods were asked to complete a verbal autopsy interview. Expert algorithms with two different hierarchies were used to assign causes of neonatal death, varying in placement of the preterm/low birth weight category within the hierarchy (either third or last). The main outcome measure was cause-specific neonatal mortality. RESULT: Deaths because of serious infections in the home-care arm declined from 13.6 deaths per 1000 live births during the baseline period to 7.2 during the intervention period according to the first hierarchy (preterm placed third) and from 23.6 to 10.6 according to the second hierarchy (preterm placed last). CONCLUSION: This study confirms the high burden of neonatal deaths because of infection in low resource rural settings like Bangladesh, where most births occur at home in the absence of skilled birth attendance and care seeking for newborn illnesses is low. The study demonstrates that a package of community-based neonatal health interventions, focusing primarily on infection prevention and management, can substantially reduce infection-related neonatal mortality. PMID- 26540249 TI - Pulse oximetry screening for critical congenital heart disease in the neonatal intensive care unit. AB - OBJECTIVE: Pulse oximetry screening (POS) is an effective tool to detect critical congenital heart disease (CCHD) in asymptomatic term infants, but its value in the neonatal intensive care unit (NICU) requires further clarification. STUDY DESIGN: A retrospective review of 1005 babies without previously diagnosed CCHD admitted to a level III NICU was performed to assess the risk for missed CCHD and performance of POS. RESULT: Of the 1005 NICU patients, 812 had documented POS and none failed POS. In 812 patients, 547 had delayed POS because of the use of supplemental oxygen. In 259/812 patients, POS was delayed until the baby was >2 weeks old. CCHD was excluded by echocardiography, irrespective of POS, in 287/1005 patients. CONCLUSION: POS can be performed in the NICU with minimal adverse effects. However, in many NICU patients CCHD is confirmed or excluded before POS, and POS will frequently be performed after CCHD would have been expected to become symptomatic. PMID- 26540250 TI - Increased monocytes and bands following a red blood cell transfusion. AB - OBJECTIVE: The objective of this study is to analyze the white blood cell changes that occur after a transfusion of red blood cells in order to identify a subclinical inflammatory response in neonates. STUDY DESIGN: Retrospective analysis of infants who received a red blood cell transfusion in an intensive care nursery. White blood cell results within 24 h pre- to 48 h post-transfusion were collected and analyzed. Statistical analysis included ANOVA, T-test, Mann Whitney U test, Pearson's correlation and multivariable linear regression. RESULT: Monocytes (P=0.02) and bands (P=0.035) were increased post-transfusion. There were no differences in monocytes (P=0.46) or bands (P=0.56) between groups who did or did not have blood cultures obtained. There was no difference in monocytes between groups who did or did not have sepsis (P=0.88). CONCLUSION: We identified an elevation in monocytes and bands in the 48 h following a transfusion in premature infants. Our findings support a possible pro inflammatory response related to transfusion of red blood cells. PMID- 26540251 TI - A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants? AB - BACKGROUND: Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. METHODS: Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. RESULTS: There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. CONCLUSION: The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers. PMID- 26540253 TI - High Strain Rate Tensile Testing of Silver Nanowires: Rate-Dependent Brittle-to Ductile Transition. AB - The characterization of nanomaterials under high strain rates is critical to understand their suitability for dynamic applications such as nanoresonators and nanoswitches. It is also of great theoretical importance to explore nanomechanics with dynamic and rate effects. Here, we report in situ scanning electron microscope (SEM) tensile testing of bicrystalline silver nanowires at strain rates up to 2/s, which is 2 orders of magnitude higher than previously reported in the literature. The experiments are enabled by a microelectromechanical system (MEMS) with fast response time. It was identified that the nanowire plastic deformation has a small activation volume (<10b(3)), suggesting dislocation nucleation as the rate controlling mechanism. Also, a remarkable brittle-to ductile failure mode transition was observed at a threshold strain rate of 0.2/s. Transmission electron microscopy (TEM) revealed that along the nanowire, dislocation density and spatial distribution of plastic regions increase with increasing strain rate. Furthermore, molecular dynamic (MD) simulations show that deformation mechanisms such as grain boundary migration and dislocation interactions are responsible for such ductility. Finally, the MD and experimental results were interpreted using dislocation nucleation theory. The predicted yield stress values are in agreement with the experimental results for strain rates above 0.2/s when ductility is pronounced. At low strain rates, random imperfections on the nanowire surface trigger localized plasticity, leading to a brittle-like failure. PMID- 26540252 TI - Compensatory Response by Late Embryonic Tubular Epithelium to the Reduction in Pancreatic Progenitors. AB - Early in pancreatic development, epithelial cells of pancreatic buds function as primary multipotent progenitor cells (1 degrees MPC) that specify all three pancreatic cell lineages, i.e., endocrine, acinar and duct. Bipotent "Trunk" progenitors derived from 1 degrees MPC are implicated in directly regulating the specification of endocrine progenitors. It is unclear if this specification process is initiated in the 1 degrees MPC where some 1 degrees MPC become competent for later specification of endocrine progenitors. Previously we reported that in Pdx1tTA/+;tetOMafA (bigenic) mice inducing expression of transcription factor MafA in Pdx1-expressing (Pdx1+) cells throughout embryonic development inhibited the proliferation and differentiation of 1 degrees MPC cells, resulting in reduced pancreatic mass and endocrine cells by embryonic day (E) 17.5. Induction of the transgene only until E12.5 in Pdx1+ 1 degrees MPC was sufficient for this inhibition of endocrine cells and pancreatic mass at E17.5. However, by birth (P0), as we now report, such bigenic pups had significantly increased pancreatic and endocrine volumes with endocrine clusters containing all pancreatic endocrine cell types. The increase in endocrine cells resulted from a higher proliferation of tubular epithelial cells expressing the progenitor marker Glut2 in E17.5 bigenic embryos and increased number of Neurog3-expressing cells at E19.5. A BrdU-labeling study demonstrated that inhibiting proliferation of 1 degrees MPC by forced MafA-expression did not lead to retention of those progenitors in E17.5 tubular epithelium. Our data suggest that the forced MafA expression in the 1 degrees MPC inhibits their competency to specify endocrine progenitors only until E17.5, and after that compensatory proliferation of tubular epithelium gives rise to a distinct pool of endocrine progenitors. Thus, these bigenic mice provide a novel way to characterize the competency of 1 degrees MPC for their ability to specify endocrine progenitors, a critical limitation in our understanding of endocrine differentiation. PMID- 26540254 TI - Salmonella Prevalence and Antimicrobial Susceptibility from the National Animal Health Monitoring System Sheep 2011 Study. AB - Salmonella is a major cause of foodborne illness and can cause clinical disease in animals. Understanding the on-farm ecology of Salmonella will be helpful in decreasing the risk of foodborne transmission. An objective of this study was to determine the prevalence of Salmonella among fecal samples collected on sheep operations in the United States. Another objective was to compare the use of composite fecal samples with fecal samples collected from individual sheep as a tool for screening sheep flocks for Salmonella. Sheep fecal samples (individual and composite) were collected on operations in 22 states. Salmonella isolates were characterized with regard to species, serotype, and antimicrobial susceptibility profile. Most operations (72.1%) had at least one positive sample and overall 26.9% of samples were positive. The percentage of positive samples varied by animal age class. Composite and individual samples gave similar results. The majority of the isolates (94%) were Salmonella enterica subspecies diarizonae serotype 61:-:1,5,7. Nearly all of the isolates (91.2%) tested for antimicrobial susceptibility were susceptible to all antimicrobials in the panel. The findings suggest that salmonellae typically associated with foodborne disease transmission are infrequently found on sheep operations in the United States. PMID- 26540255 TI - Members of the RAD52 Epistasis Group Contribute to Mitochondrial Homologous Recombination and Double-Strand Break Repair in Saccharomyces cerevisiae. AB - Mitochondria contain an independently maintained genome that encodes several proteins required for cellular respiration. Deletions in the mitochondrial genome have been identified that cause several maternally inherited diseases and are associated with certain cancers and neurological disorders. The majority of these deletions in human cells are flanked by short, repetitive sequences, suggesting that these deletions may result from recombination events. Our current understanding of the maintenance and repair of mtDNA is quite limited compared to our understanding of similar events in the nucleus. Many nuclear DNA repair proteins are now known to also localize to mitochondria, but their function and the mechanism of their action remain largely unknown. This study investigated the contribution of the nuclear double-strand break repair (DSBR) proteins Rad51p, Rad52p and Rad59p in mtDNA repair. We have determined that both Rad51p and Rad59p are localized to the matrix of the mitochondria and that Rad51p binds directly to mitochondrial DNA. In addition, a mitochondrially-targeted restriction endonuclease (mtLS-KpnI) was used to produce a unique double-strand break (DSB) in the mitochondrial genome, which allowed direct analysis of DSB repair in vivo in Saccharomyces cerevisiae. We find that loss of these three proteins significantly decreases the rate of spontaneous deletion events and the loss of Rad51p and Rad59p impairs the repair of induced mtDNA DSBs. PMID- 26540256 TI - An improved optical flow tracking technique for real-time MR-guided beam therapies in moving organs. AB - Magnetic resonance (MR) guided high intensity focused ultrasound and external beam radiotherapy interventions, which we shall refer to as beam therapies/interventions, are promising techniques for the non-invasive ablation of tumours in abdominal organs. However, therapeutic energy delivery in these areas becomes challenging due to the continuous displacement of the organs with respiration. Previous studies have addressed this problem by coupling high framerate MR-imaging with a tracking technique based on the algorithm proposed by Horn and Schunck (H and S), which was chosen due to its fast convergence rate and highly parallelisable numerical scheme. Such characteristics were shown to be indispensable for the real-time guidance of beam therapies. In its original form, however, the algorithm is sensitive to local grey-level intensity variations not attributed to motion such as those that occur, for example, in the proximity of pulsating arteries.In this study, an improved motion estimation strategy which reduces the impact of such effects is proposed. Displacements are estimated through the minimisation of a variation of the H and S functional for which the quadratic data fidelity term was replaced with a term based on the linear L(1)norm, resulting in what we have called an L(2)-L(1) functional.The proposed method was tested in the livers and kidneys of two healthy volunteers under free breathing conditions, on a data set comprising 3000 images equally divided between the volunteers. The results show that, compared to the existing approaches, our method demonstrates a greater robustness to local grey-level intensity variations introduced by arterial pulsations. Additionally, the computational time required by our implementation make it compatible with the work-flow of real-time MR-guided beam interventions.To the best of our knowledge this study was the first to analyse the behaviour of an L(1)-based optical flow functional in an applicative context: real-time MR-guidance of beam therapies in moving organs. PMID- 26540258 TI - (135)Cs/(137)Cs isotopic composition of environmental samples across Europe: Environmental transport and source term emission applications. AB - (135)Cs/(137)Cs isotopic analyses represent an important tool for studying the fate and transport of radiocesium in the environment; in this work the (135)Cs/(137)Cs isotopic composition in environmental samples taken from across Europe is reported. Surface soil and vegetation samples from western Russia, Ukraine, Austria, and Hungary show consistent aged thermal fission product (135)Cs/(137)Cs isotope ratios of 0.58 +/- 0.01 (age corrected to 1/1/15), with the exception of one sample of soil-moss from Hungary which shows an elevated (135)Cs/(137)Cs ratio of 1.78 +/- 0.12. With the exception of the outlier sample from Hungary, surface soil/vegetation data are in quantitative agreement with values previously reported for soils within the Chernobyl exclusion zone, suggesting that radiocesium at these locations is primarily composed of homogenous airborne deposition from Chernobyl. Seawater samples taken from the Irish Sea show (135)Cs/(137)Cs isotope ratios of 1.22 +/- 0.11 (age corrected to 1/1/15), suggesting aged thermal fission product Cs discharged from Sellafield. The differences in (135)Cs/(137)Cs isotope ratios between Sellafield, Chernobyl, and global nuclear weapons testing fallout indicate that (135)Cs/(137)Cs isotope ratios can be utilized to discriminate between and track radiocesium transport from different nuclear production source terms, including major emission sources in Europe. PMID- 26540257 TI - The complete mitochondrial genome of Garra kempi (Teleostei, Cyprinidae, Garra). AB - Garra kempi, a small-sized economic fish, is mainly distributed in Tibet of China. In this study, we successfully sequenced the first mitochondrial genome of G. kempi. The mitogenome is 17 104 bp in length, containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and 2 control regions (D-loop). Unlike the typical mitochondrial genome organization in vertebrate, the tRNAPro gene of G. kempi is located between two control regions, and a 246 bp repeat unit is identified in the second control region. In this paper, we utilized 12 protein coding genes of G. kempi and other 10 closely species to construct the species phylogenetic tree to verify the accuracy of G. kempi. PMID- 26540259 TI - Fluctuations in Pigment Epithelial Detachment and Retinal Fluid Using a Bimonthly Treatment Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration. AB - PURPOSE: To assess the effect of a bimonthly treatment regimen with intravitreal aflibercept on retinal fluid and pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (AMD). METHODS: Twenty-six treatment-naive eyes of 26 patients with choroidal neovascularisation secondary to AMD were included. The patients received three initial monthly (mean 30 days) intravitreal injections of aflibercept followed by a bimonthly (mean 62 days) fixed regimen for a total of 1 year. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were recorded at monthly intervals. In addition, the presence of intraretinal fluid (IRF) or subretinal fluid (SRF) or a combination of both as well as serous and fibrovascular PEDs were assessed. RESULTS: The mean patient age was 80 years (range 54-93). There were 14 male and 12 female patients. The mean gain in BCVA at 1 year was 9.3 letters (SEM +/-3) with a mean reduction of the central retinal thickness of 154 um (SEM +/-50). After 3 monthly injections of aflibercept, there was resolution of IRF and SRF in 80% of the treated eyes; the amount of fluid increased at months 4, 6 and 8 with troughs in between. Whereas fibrovascular PEDs remained stable after the loading phase, serous PEDs displayed a seesaw pattern. Patients without retinal pigment epithelium (RPE) atrophy at the end of the 1-year period had significantly better BCVA compared to patients with RPE atrophy (p = 0.03). CONCLUSION: Despite significant overall BCVA gain, bimonthly intervals seem insufficient to maintain the morphological improvements after the initial loading dose with intravitreal aflibercept. PMID- 26540261 TI - Effects of Oral Contraceptive Use on Anterior Cruciate Ligament Injury Epidemiology. AB - INTRODUCTION/PURPOSE: Anterior cruciate ligament injuries often incur major consequences for athletes. Elevated estrogen levels are likely increase the risk for injury. This risk may be partially or fully mitigated by the use of oral contraceptives. The purpose of this study was to determine if women undergoing anterior cruciate ligament surgical reconstruction were less likely to use oral contraceptives than matched noninjured population. METHODS: This is a case control study utilizing national insurance claims data from 2002 TO 2012. Participants included women age 15-39 yr. Cases were defined as those receiving surgical reconstruction of the anterior cruciate ligament between 2002 and 2012. Controls were matched 3/1 to cases. Exposure to oral contraceptives was defined as the presence of any prescription fill for oral contraceptives during the previous 12 months to index date. Conditional multivariate logistic regression was used to estimate adjusted odds ratios for the use of oral contraceptives. RESULTS: Women age 15-19 yr undergoing surgical repair of the anterior cruciate ligament were 18% less likely to use oral contraceptives than matched controls (adjusted odds ratio, 0.82; 95% CI, 0.75-0.91; P < 0.0001). Cases among two older age groups, 25-29 and 30-34 yr, were more likely to use oral contraceptives than controls with adjusted odds ratios of 1.15 (95% CI, 1.02-1.30; P < 0.05) and 1.16 (95% CI, 1.04-1.31; P < 0.05), respectively. CONCLUSIONS: The use of oral contraceptives potentially modifies anterior cruciate ligament injury risk in young women. Despite reports that athletes, who are more prone to anterior cruciate ligament injury, use oral contraceptives at about twice the rate of nonathletes, these data suggest that women ages 15-19 yr undergoing anterior cruciate ligament reconstruction used oral contraceptives at a lower rate than the general population. PMID- 26540260 TI - Emergence and Characterization of Unusual DS-1-Like G1P[8] Rotavirus Strains in Children with Diarrhea in Thailand. AB - The emergence and rapid spread of unusual DS-1-like G1P[8] rotaviruses in Japan have been recently reported. During rotavirus surveillance in Thailand, three DS 1-like G1P[8] strains (RVA/Human-wt/THA/PCB-180/2013/G1P[8], RVA/Human-wt/THA/SKT 109/2013/G1P[8], and RVA/Human-wt/THA/SSKT-41/2013/G1P[8]) were identified in stool specimens from hospitalized children with severe diarrhea. In this study, we sequenced and characterized the complete genomes of strains PCB-180, SKT-109, and SSKT-41. On whole genomic analysis, all three strains exhibited a unique genotype constellation including both genogroup 1 and 2 genes: G1-P[8]-I2-R2-C2 M2-A2-N2-T2-E2-H2. This novel genotype constellation is shared with Japanese DS-1 like G1P[8] strains. Phylogenetic analysis revealed that the G/P genes of strains PCB-180, SKT-109, and SSKT-41 appeared to have originated from human Wa-like G1P[8] strains. On the other hand, the non-G/P genes of the three strains were assumed to have originated from human DS-1-like strains. Thus, strains PCB-180, SKT-109, and SSKT-41 appeared to be derived through reassortment event(s) between Wa-like G1P[8] and DS-1-like human rotaviruses. Furthermore, strains PCB-180, SKT 109, and SSKT-41 were found to have the 11-segment genome almost indistinguishable from one another in their nucleotide sequences and phylogenetic lineages, indicating the derivation of the three strains from a common origin. Moreover, all the 11 genes of the three strains were closely related to those of Japanese DS-1-like G1P[8] strains. Therefore, DS-1-like G1P[8] strains that have emerged in Thailand and Japan were assumed to have originated from a recent common ancestor. To our knowledge, this is the first report on whole genome-based characterization of DS-1-like G1P[8] strains that have emerged in an area other than Japan. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G1P[8] rotaviruses. PMID- 26540262 TI - Similar Hemoglobin Mass Response in Hypobaric and Normobaric Hypoxia in Athletes. AB - PURPOSE: To compare hemoglobin mass (Hb(mass)) changes during an 18-d live high train low (LHTL) altitude training camp in normobaric hypoxia (NH) and hypobaric hypoxia (HH). METHODS: Twenty-eight well-trained male triathletes were split into three groups (NH: n = 10, HH: n = 11, control [CON]: n = 7) and participated in an 18-d LHTL camp. NH and HH slept at 2250 m, whereas CON slept, and all groups trained at altitudes <1200 m. Hb(mass) was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre-), immediately after (post-) (hypoxic dose: 316 vs 238 h for HH and NH), and at day 13 in HH (230 h, hypoxic dose matched to 18-d NH). Running (3-km run) and cycling (incremental cycling test) performances were measured pre and post. RESULTS: Hb(mass) increased similar in HH (+4.4%, P < 0.001 at day 13; +4.5%, P < 0.001 at day 18) and NH (+4.1%, P < 0.001) compared with CON (+1.9%, P = 0.08). There was a wide variability in individual Hb(mass) responses in HH (-0.1% to +10.6%) and NH ( 1.4% to +7.7%). Postrunning time decreased in HH (-3.9%, P < 0.001), NH (-3.3%, P < 0.001), and CON (-2.1%, P = 0.03), whereas cycling performance changed nonsignificantly in HH and NH (+2.4%, P > 0.08) and remained unchanged in CON (+0.2%, P = 0.89). CONCLUSION: HH and NH evoked similar Hb(mass) increases for the same hypoxic dose and after 18-d LHTL. The wide variability in individual Hb(mass) responses in HH and NH emphasizes the importance of individual Hb(mass) evaluation of altitude training. PMID- 26540263 TI - Immediate Effects of Aerobic Exercise on Plasma/Serum Zinc Levels: A Meta analysis. AB - BACKGROUND: Zinc is involved in numerous metabolic roles, including energy metabolism, immunity, and antioxidative effects. Zinc losses during exercise, in particular through sweat, are well documented. However, conflicting results have been reported for changes in circulating and tissue zinc concentration as a result of exercise. The purpose of this article is to quantify the immediate effect of aerobic exercise on plasma or serum zinc levels, in healthy participants. METHODS: We conducted a systematic review of peer-reviewed articles published up to December 20, 2014, to identify studies that investigated the acute effects of exercise on selected indices of zinc status. Meta-analyses were conducted to determine the change in serum zinc concentration immediately after a bout of aerobic exercise. RESULTS: Forty-five studies were included in the systematic literature review. Of the included studies, sufficient data were available from 34 studies (providing 46 comparisons) to quantify the change in serum zinc concentration after exercise. Serum zinc concentration was significantly higher immediately after exercise (0.45 +/- 0.12 MUmol.L(-1), P < 0.001; mean +/- SE). Secondary analyses showed greater increase in serum zinc for untrained individuals and exercise sessions that involved running or maximal intensity. Insufficient data were available to determine the effects of exercise on urinary, sweat, and erythrocyte zinc. CONCLUSIONS: The present systematic review and meta-analysis indicated significant increase in serum zinc concentration immediately after an aerobic exercise session, suggesting acute perturbations in zinc homeostasis. Further research is required to ascertain the long-term effects of exercise on zinc metabolism and potential consequences for dietary zinc requirement for physically active populations. PMID- 26540264 TI - Effects of Taping and Orthoses on Foot Biomechanics in Adults with Flat-Arched Feet. AB - PURPOSE: There is a paucity of evidence on the biomechanical effects of foot taping and foot orthoses in realistic conditions. This study aimed to determine the immediate effect and relationships between changes in multisegment foot biomechanics with foot taping and customized foot orthoses in adults with flat arched feet. METHODS: Multisegment foot biomechanics were measured in 18 adults with flat-arched feet (age 25.1 +/- 2.8 yr; height 1.73 +/- .13 m, body mass 70.3 +/- 15.7 kg) during walking in four conditions in random order: neutral athletic shoe, neutral shoe with tape (low-Dye method and modified method) and neutral shoe with customized foot orthoses. In-shoe foot biomechanics were compared between conditions using a purpose developed foot model with three-dimensional kinematic analysis and inverse dynamics. RESULTS: Foot orthoses significantly delayed peak eversion compared to the neutral shoe (44% stance vs 39%, P = 0.002). Deformation across the midfoot and medial longitudinal arch was reduced with both the low-Dye taping (2.4 degrees , P < 0.001) and modified taping technique (5.5 degrees , P < 0.001). All interventions increased peak dorsiflexion of the first metatarsophalangeal joint (1.4 degrees -3.2 degrees , P < 0.001-0.023). Biomechanical responses to taping significantly predicted corresponding changes to foot orthoses (R2 = 0.08-0.52, P = 0.006 to <0.001). CONCLUSIONS: Foot orthoses more effectively altered timing of hindfoot motion whereas taping was superior in supporting the midfoot and medial longitudinal arch. The biomechanical response to taping was significantly related to the subsequent change observed with the use of foot orthoses. PMID- 26540265 TI - Photocatalytic and photoelectrocatalytic reduction of CO2 using heterogeneous catalysts with controlled nanostructures. AB - The development of efficient artificial photocatalysts and photoelectrocatalysts for the reduction of CO2 with H2O to fuels and chemicals has attracted much attention in recent years. Although the state-of-the-art for the production of fuels or chemicals from CO2 using solar energy is still far from practical consideration, rich knowledge has been accumulated to understand the key factors that determine the catalytic performances. This Feature article highlights recent advances in the photocatalytic and photoelectrocatalytic reduction of CO2 with H2O using heterogeneous semiconductor-based catalysts. The effects of structural aspects of semiconductors, such as crystalline phases, particle sizes, morphologies, exposed facets and heterojunctions, on their catalytic behaviours are discussed. The roles of different types of cocatalysts and the impact of their nanostructures on surface CO2 chemisorption and reduction are also analysed. The present article aims to provide insights into the rational design of efficient heterogeneous catalysts with controlled nanostructures for the photocatalytic and photoelectrocatalytic reduction of CO2 with H2O. PMID- 26540266 TI - Molecular Characterization and Differential Expression of an Olfactory Receptor Gene Family in the White-Backed Planthopper Sogatella furcifera Based on Transcriptome Analysis. AB - The white-backed planthopper, Sogatella furcifera, a notorious rice pest in Asia, employs host plant volatiles as cues for host location. In insects, odor detection is mediated by two types of olfactory receptors: odorant receptors (ORs) and ionotropic receptors (IRs). In this study, we identified 63 SfurORs and 14 SfurIRs in S. furcifera based on sequences obtained from the head transcriptome and bioinformatics analysis. The motif-pattern of 130 hemiptera ORs indicated an apparent differentiation in this order. Phylogenetic trees of the ORs and IRs were constructed using neighbor-joining estimates. Most of the ORs had orthologous genes, but a specific OR clade was identified in S. furcifera, which suggests that these ORs may have specific olfactory functions in this species. Our results provide a basis for further investigations of how S. furcifera coordinates its olfactory receptor genes with its plant hosts, thereby providing a foundation for novel pest management approaches based on these genes. PMID- 26540268 TI - Correction: Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate. PMID- 26540267 TI - Bimanual motor coordination controlled by cooperative interactions in intrinsic and extrinsic coordinates. AB - Although strong motor coordination in intrinsic muscle coordinates has frequently been reported for bimanual movements, coordination in extrinsic visual coordinates is also crucial in various bimanual tasks. To explore the bimanual coordination mechanisms in terms of the frame of reference, here we characterized implicit bilateral interactions in visuomotor tasks. Visual perturbations (finger cursor gain change) were applied while participants performed a rhythmic tracking task with both index fingers under an in-phase or anti-phase relationship in extrinsic coordinates. When they corrected the right finger's amplitude, the left finger's amplitude unintentionally also changed [motor interference (MI)], despite the instruction to keep its amplitude constant. Notably, we observed two specificities: one was large MI and low relative-phase variability (PV) under the intrinsic in-phase condition, and the other was large MI and high PV under the extrinsic in-phase condition. Additionally, using a multiple-interaction model, we successfully decomposed MI into intrinsic components caused by motor correction and extrinsic components caused by visual-cursor mismatch of the right finger's movements. This analysis revealed that the central nervous system facilitates MI by combining intrinsic and extrinsic components in the condition with in-phases in both intrinsic and extrinsic coordinates, and that under additivity of the effects is explained by the brain's preference for the intrinsic interaction over extrinsic interaction. In contrast, the PV was significantly correlated with the intrinsic component, suggesting that the intrinsic interaction dominantly contributed to bimanual movement stabilization. The inconsistent features of MI and PV suggest that the central nervous system regulates multiple levels of bilateral interactions for various bimanual tasks. PMID- 26540269 TI - The mTOR Inhibitor Rapamycin Mitigates Perforant Pathway Neurodegeneration and Synapse Loss in a Mouse Model of Early-Stage Alzheimer-Type Tauopathy. AB - The perforant pathway projection from layer II of the entorhinal cortex to the hippocampal dentate gyrus is especially important for long-term memory formation, and is preferentially vulnerable to developing a degenerative tauopathy early in Alzheimer's disease (AD) that may spread over time trans-synaptically. Despite the importance of the perforant pathway to the clinical onset and progression of AD, a therapeutic has not been identified yet that protects it from tau-mediated toxicity. Here, we used an adeno-associated viral vector-based mouse model of early-stage AD-type tauopathy to investigate effects of the mTOR inhibitor and autophagy stimulator rapamycin on the tau-driven loss of perforant pathway neurons and synapses. Focal expression of human tau carrying a P301L mutation but not eGFP as a control in layer II of the lateral entorhinal cortex triggered rapid degeneration of these neurons, loss of lateral perforant pathway synapses in the dentate gyrus outer molecular layer, and activation of neuroinflammatory microglia and astroglia in the two locations. Chronic systemic rapamycin treatment partially inhibited phosphorylation of a mechanistic target of rapamycin substrate in brain and stimulated LC3 cleavage, a marker of autophagic flux. Compared with vehicle-treated controls, rapamycin protected against the tau induced neuronal loss, synaptotoxicity, reactive microgliosis and astrogliosis, and activation of innate neuroimmunity. It did not alter human tau mRNA or total protein levels. Finally, rapamycin inhibited trans-synaptic transfer of human tau expression to the dentate granule neuron targets for the perforant pathway, likely by preventing the synaptic spread of the AAV vector in response to pathway degeneration. These results identify systemic rapamycin as a treatment that protects the entorhinal cortex and perforant pathway projection from tau-mediated neurodegeneration, axonal and synapse loss, and neuroinflammatory reactive gliosis. The findings support the potential for slowing the progression of AD by abrogating tau-mediated neurotoxicity at its earliest neuropathological stages. PMID- 26540270 TI - Transcriptomic Analysis of Myocardial Ischemia Using the Blood of Rat. AB - Myocardial ischemia is a pathological state of heart with reduced blood flow to heart and abnormal myocardial energy metabolism. This disease occurs commonly in middle aged and elderly people. Several studies have indicated that the rat was an appropriate animal model used to study myocardial ischemia. In this study, in order to gain insights into the pathogenesis of myocardial ischemia, we sequenced the transcriptomes of three normal rats as control and the same number of myocardial ischemia rats. We sequenced the genomes of 6 rats, including 3 cases (myocardial ischemia) and 3 controls using Illumina HiSeq 2000. Then we calculated the gene expression values and identified differentially expressed genes based on reads per kilobase transcriptome per million (RPKM). Meanwhile we performed a GO enrichment analysis and predicted novel transcripts. In our study, we found that 707 genes were up-regulated and 21 genes were down-regulated in myocardial ischemia rats by at least 2-fold compared with controls. By the distribution of reads and the annotation of reference genes, we found 1,703 and 1,552 novel transcripts in cases and controls, respectively. At the same time, we refined the structure of 9,587 genes in controls and 10,301 in cases. According to the results of GO term and pathway analysis of differentially expressed genes, we found that the immune response, stimulus response, response to stress and some diseases may be associated with myocardial ischemia. Since many diseases, especially immune diseases, are associated with myocardial ischemia, we should pay more attention to the complications which might result from myocardial ischemia. PMID- 26540271 TI - Carbon Catabolite Repression and the Related Genes of ccpA, ptsH and hprK in Thermoanaerobacterium aotearoense. AB - The strictly anaerobic, Gram-positive bacterium, Thermoanaerobacterium aotearoense SCUT27, is capable of producing ethanol, hydrogen and lactic acid by directly fermenting glucan, xylan and various lignocellulosically derived sugars. By using non-metabolizable and metabolizable sugars as substrates, we found that cellobiose, galactose, arabinose and starch utilization was strongly inhibited by the existence of 2-deoxyglucose (2-DG). However, the xylose and mannose consumptions were not markedly affected by 2-DG at the concentration of one-tenth of the metabolizable sugar. Accordingly, T. aotearoense SCUT27 could consume xylose and mannose in the presence of glucose. The carbon catabolite repression (CCR) related genes, ccpA, ptsH and hprK were confirmed to exist in T. aotearoense SCUT27 through gene cloning and protein characterization. The highly purified Histidine-containing Protein (HPr) could be specifically phosphorylated at Serine 46 by HPr kinase/phosphatase (HPrK/P) with no need to add fructose-1,6 bisphosphate (FBP) or glucose-6-phosphate (Glc-6-P) in the reaction mixture. The specific protein-interaction of catabolite control protein A (CcpA) and phosphorylated HPr was proved via affinity chromatography in the absence of formaldehyde. The equilibrium binding constant (KD) of CcpA and HPrSerP was determined as 2.22 +/- 0.36 nM by surface plasmon resonance (SPR) analysis, indicating the high affinity between these two proteins. PMID- 26540272 TI - DNA barcoding identification of Dermestidae species. AB - Dermestidae species are important stored product insects. The traditional morphological identification has its limitation. The purpose of the study is to explore the effectiveness of identification by DNA barcoding technology in Dermestidae. The COI gene sequences of 39 samples from 17 species of Dermestidae were analyzed, and we evaluated the identification ability of the sequences by the tree building method and the distance evaluation method in this study. The COI sequences whose length was 356 bp had a large difference between intra specific and inter-specific and a significant barcoding gap. The success rate of identification was 92.5%. The results showed a certain feasibility to identify the most species of Dermestidae by this segment of COI. PMID- 26540273 TI - Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States. AB - Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a "silent killer," it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications. PMID- 26540274 TI - Sparse/Low Rank Constrained Reconstruction for Dynamic PET Imaging. AB - In dynamic Positron Emission Tomography (PET), an estimate of the radio activity concentration is obtained from a series of frames of sinogram data taken at ranging in duration from 10 seconds to minutes under some criteria. So far, all the well-known reconstruction algorithms require known data statistical properties. It limits the speed of data acquisition, besides, it is unable to afford the separated information about the structure and the variation of shape and rate of metabolism which play a major role in improving the visualization of contrast for some requirement of the diagnosing in application. This paper presents a novel low rank-based activity map reconstruction scheme from emission sinograms of dynamic PET, termed as SLCR representing Sparse/Low Rank Constrained Reconstruction for Dynamic PET Imaging. In this method, the stationary background is formulated as a low rank component while variations between successive frames are abstracted to the sparse. The resulting nuclear norm and l1 norm related minimization problem can also be efficiently solved by many recently developed numerical methods. In this paper, the linearized alternating direction method is applied. The effectiveness of the proposed scheme is illustrated on three data sets. PMID- 26540275 TI - Self-assembly of phospholipids on flat supports. AB - The current study deals with the self-assembly of phospholipids on flat supports using the Martini coarse grain model. We reported here the effect of the hydrophilic and hydrophobic nature of the solid supports on the lipid self assembly. The hydrophilic and hydrophobic supports were modeled on the basis of water droplet simulations. The present work addresses the self-assembly mechanism of lipids on eight different supports with different strengths of hydrophilicity and hydrophobicity. We demonstrated how interplay between the interactions of lipid and water with the support can guide the lipid self-assembly process. Thereafter, we calculated the energetics of the components of the system to quantify the competitions between water and a lipid head-group with hydrophilic supports. Finally, the properties of the self-assembled bilayers were also analyzed and reported here. PMID- 26540276 TI - New Applications for Traditional Drugs in Inflammatory Bowel Disease: What Do Cochrane Reviews Tell Us? AB - Although multiple innovative treatments of inflammatory bowel disease have become available, research continues to refine the value of existing drug therapies for Crohn's disease and ulcerative colitis. What can Cochrane reviews tell us about evolving applications for traditional agents in inflammatory bowel disease? A Cochrane Collaboration symposium held at the 2014 Digestive Diseases Week annual meeting addressed this question. This article reviews the data presented at that session. PMID- 26540277 TI - Reduced Numbers and Proapoptotic Features of Mucosal-associated Invariant T Cells as a Characteristic Finding in Patients with Inflammatory Bowel Disease. PMID- 26540278 TI - Reply: To PMID 25946569. PMID- 26540280 TI - Error in Data. PMID- 26540279 TI - Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae. AB - Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the alpha helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID- 26540281 TI - Treatment of Retinal Vein Occlusion with Ranibizumab in Clinical Practice: Longer Term Results and Predictive Factors of Functional Outcome. AB - PURPOSE: To evaluate long-term results and predictors of efficacy in patients with macular edema due to retinal vein occlusion (RVO) treated with intravitreal ranibizumab in a clinical practice setting. METHODS: The clinical records of patients with a minimum follow-up of 3 years were retrospectively analyzed. Sixteen eyes with branch RVO (BRVO) and 16 with central RVO (CRVO) were included. All patients performed cross-sectional evaluation with best-corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescein angiography. The foveal avascular zone (FAZ) was assessed and microstructural morphology of the retina was characterized. RESULTS: Follow- up was 42.9 +/- 9.0 and 44.8 +/- 8.0 months in the CRVO and BRVO groups, respectively. Patients with CRVO received on average 6.9 injections, with a final VA gain of 8.3 +/- 15.0 letters (p = 0.05). BRVO eyes had on average 5.9 injections, with a final VA gain of 1.6 +/- 21.0 letters (p > 0.05). The FAZ area remained stable in both groups (p > 0.05). Baseline BCVA and disruption of the retinal pigment epithelium (RPE) were predictors of final BCVA (p = 0.001 and 0.011, respectively). CONCLUSION: Although functional outcomes were inferior to those reported in clinical trials, ranibizumab was satisfactory in the long-term treatment of macular edema secondary to RVO and was not associated with increased macular ischemia. Final BCVA depends on baseline BCVA and RPE integrity. PMID- 26540283 TI - Seizures in Children and Adolescents Aged 6-17 Years - United States, 2010-2014. PMID- 26540282 TI - Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs. AB - Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs. PMID- 26540285 TI - Dissecting Long-Term Glucose Metabolism Identifies New Susceptibility Period for Metabolic Dysfunction in Aged Mice. AB - Metabolic disorders, like diabetes and obesity, are pathogenic outcomes of imbalance in glucose metabolism. Nutrient excess and mitochondrial imbalance are implicated in dysfunctional glucose metabolism with age. We used conplastic mouse strains with defined mitochondrial DNA (mtDNA) mutations on a common nuclear genomic background, and administered a high-fat diet up to 18 months of age. The conplastic mouse strain B6-mtFVB, with a mutation in the mt-Atp8 gene, conferred beta-cell dysfunction and impaired glucose tolerance after high-fat diet. To our surprise, despite of this functional deficit, blood glucose levels adapted to perturbations with age. Blood glucose levels were particularly sensitive to perturbations at the early age of 3 to 6 months. Overall the dynamics consisted of a peak between 3-6 months followed by adaptation by 12 months of age. With the help of mathematical modeling we delineate how body weight, insulin and leptin regulate this non-linear blood glucose dynamics. The model predicted a second rise in glucose between 15 and 21 months, which could be experimentally confirmed as a secondary peak. We therefore hypothesize that these two peaks correspond to two sensitive periods of life, where perturbations to the basal metabolism can mark the system for vulnerability to pathologies at later age. Further mathematical modeling may perspectively allow the design of targeted periods for therapeutic interventions and could predict effects on weight loss and insulin levels under conditions of pre-diabetic obesity. PMID- 26540284 TI - Identification of Putative Olfactory Genes from the Oriental Fruit Moth Grapholita molesta via an Antennal Transcriptome Analysis. AB - BACKGROUND: The oriental fruit moth, Grapholita molesta, is an extremely important oligophagous pest species of stone and pome fruits throughout the world. As a host-switching species, adult moths, especially females, depend on olfactory cues to a large extent in locating host plants, finding mates, and selecting oviposition sites. The identification of olfactory genes can facilitate investigation on mechanisms for chemical communications. METHODOLOGY/PRINCIPAL FINDING: We generated transcriptome of female antennae of G.molesta using the next-generation sequencing technique, and assembled transcripts from RNA-seq reads using Trinity, SOAPdenovo-trans and Abyss-trans assemblers. We identified 124 putative olfactory genes. Among the identified olfactory genes, 118 were novel to this species, including 28 transcripts encoding for odorant binding proteins, 17 chemosensory proteins, 48 odorant receptors, four gustatory receptors, 24 ionotropic receptors, two sensory neuron membrane proteins, and one odor degrading enzyme. The identified genes were further confirmed through semi quantitative reverse transcription PCR for transcripts coding for 26 OBPs and 17 CSPs. OBP transcripts showed an obvious antenna bias, whereas CSP transcripts were detected in different tissues. CONCLUSION: Antennal transcriptome data derived from the oriental fruit moth constituted an abundant molecular resource for the identification of genes potentially involved in the olfaction process of the species. This study provides a foundation for future research on the molecules involved in olfactory recognition of this insect pest, and in particular, the feasibility of using semiochemicals to control this pest. PMID- 26540286 TI - Treatment burden in patients with at least one class IV or V CFTR mutation. AB - CFTR mutations are grouped according to disease-causing mechanism. Several studies demonstrated that patients having at least one mutation of class IV/V, present with a milder phenotype, but little is known about their relative treatment burden. We compared treatment burden between patients with two class I, II, or III mutations and patients with at least one mutation of class IV/V in the 2010 database of the Belgian CF Registry. We calculated a "Treatment Burden Index" (TBI) by assigning long term therapies to categories low, medium and high intensity, for differential weighing in the total score. There were 779 patients with two known class I/II/III mutations and 94 patients with at least one class IV/V mutation. Compared to class I/II/III, class IV/V patients had a lower median number of clinic visits (4 vs. 5; P < 0.001), a lower risk of hospitalization (24.7% vs. 50.8%; P < 0.001) and intravenous antibiotic treatment (23.5% vs. 46.0%; P < 0.001) and a lower median TBI (6 vs. 9; P < 0.001). These differences remained significant when only class IV/V patients with pancreatic insufficiency (n = 31) were considered. This study clearly demonstrates the significantly lower treatment burden in patients with CF and at least one class IV/V mutation compared to patients with two class I/II/III mutations and contributes to providing better individual counseling at time of diagnosis. PMID- 26540288 TI - Wearable Self-Charging Power Textile Based on Flexible Yarn Supercapacitors and Fabric Nanogenerators. AB - A novel and scalable self-charging power textile is realized by combining yarn supercapacitors and fabric triboelectric nanogenerators as energy-harvesting devices. PMID- 26540287 TI - Sprouty2 and -4 hypomorphism promotes neuronal survival and astrocytosis in a mouse model of kainic acid induced neuronal damage. AB - Sprouty (Spry) proteins play a key role as negative feedback inhibitors of the Ras/Raf/MAPK/ERK pathway downstream of various receptor tyrosine kinases. Among the four Sprouty isoforms, Spry2 and Spry4 are expressed in the hippocampus. In this study, possible effects of Spry2 and Spry4 hypomorphism on neurodegeneration and seizure thresholds in a mouse model of epileptogenesis was analyzed. The Spry2/4 hypomorphs exhibited stronger ERK activation which was limited to the CA3 pyramidal cell layer and to the hilar region. The seizure threshold of Spry2/4(+/ ) mice was significantly reduced at naive state but no difference to wildtype mice was observed 1 month following KA treatment. Histomorphological analysis revealed that dentate granule cell dispersion (GCD) was diminished in Spry2/4(+/ ) mice in the subchronic phase after KA injection. Neuronal degeneration was reduced in CA1 and CA3 principal neuron layers as well as in scattered neurons of the contralateral CA1 and hilar regions. Moreover, Spry2/4 reduction resulted in enhanced survival of somatostatin and neuropeptide Y expressing interneurons. GFAP staining intensity and number of reactive astrocytes markedly increased in lesioned areas of Spry2/4(+/-) mice as compared with wildtype mice. Taken together, although the seizure threshold is reduced in naive Spry2/4(+/-) mice, neurodegeneration and GCD is mitigated following KA induced hippocampal lesions, identifying Spry proteins as possible pharmacological targets in brain injuries resulting in neurodegeneration. The present data are consistent with the established functions of the ERK pathway in astrocyte proliferation as well as protection from neuronal cell death and suggest a novel role of Spry proteins in the migration of differentiated neurons. PMID- 26540289 TI - Silk fibroin protein-based nonwoven mats incorporating baicalein Chinese herbal extract: preparation, characterizations, and in vivo evaluation. AB - In this study, we demonstrated a natural silk fibroin protein (SFP) that was blended with a Chinese herbal extract (baicalein, BAI) to obtain an effective combination for producing electrospun nonwoven mats with anti-inflammatory and antibacterial functions. A series of SFP-based electrospun nonwoven mats with additives of varying compositions were produced and investigated. Performance comparisons showed that the SFP/polyvinylpyrrolidone (PVP)/BAI nonwoven mat is the optimal one. In vitro, SFP/PVP/BAI nonwoven mat is effective in inhibiting the formation of nitrite in lipopolysaccharide (LPS)-induced nitrite formation in Raw 264.7 macrophages model and the growth of Staphylococcus aureus (S. aureus). Especially in the case of SFP/PVP/BAI nonwoven mat, Bai has been proved to reach their maximum amount of releases of approximately 64.8% within 24 h of contact with water-based environment as compared to the SFP/BAI nonwoven mat (only 30.1% of release within 24 h). For in vivo experiments, a 1.2 cm * 1.2 cm wound area was created on the back of mice and seeded with 1 * 107 CFU/mL of S. aureus to induce an infected wound model. The experimental results show significant acceleration of the wound closure process in mice treated with SFP/PVP/BAI nonwoven mat (4 days of reduction as compared to the untreated group), reduction in infiltration of neutrophils, nitrite formation, and inhibition of growth of wound bacteria. Histological images of the group treated with SFP/PVP/BAI nonwoven mat showed a compete repair of skin hierarchy, increasing production of collagen fibers, and enhancement of angiogenesis. This may bring a better recovery of skin appearance after treatment. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 420-430, 2017. PMID- 26540290 TI - Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model. AB - The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies on the effect of infarct size on temporal and spatial alterations in the myocardium during progressive myocardial remodeling. MI with three infarct sizes, i.e. 15, 25 and 35% of the left ventricular (LV) wall, was created in an ovine infarction model. The progressive LV remodeling over a 12-week period was studied. Echocardiography, sonomicrometry, and histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function, structural remodeling and cardiomyocyte hypertrophy, and calcium handling proteins. Twelve weeks after MI, the 15, 25 and 35% MI groups had normalized LV end diastole volumes of 1.4 +/- 0.2, 1.7 +/- 0.3 and 2.0 +/- 0.4 ml/kg, normalized end systole volumes of 1.0 +/- 0.1, 1.0 +/- 0.2 and 1.3 +/- 0.3 ml/kg and LV ejection fractions of 43 +/- 3, 42 +/- 6 and 34 +/- 4%, respectively. They all differed from the sham group (p < 0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. A significant correlation was found between cardiomyocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35 vs. 15% MI) was associated with larger remodeling strain, more serious impairment in the cellular structure and composition, and regional contractile function at regional tissue level and LV function at organ level. PMID- 26540292 TI - High-quality imaging in environmental scanning electron microscopy--optimizing the pressure limiting system and the secondary electron detection of a commercially available ESEM. AB - In environmental scanning electron microscopy applications in the kPa regime are of increasing interest for the investigation of wet and biological samples, because neither sample preparation nor extensive cooling are necessary. Unfortunately, the applications are limited by poor image quality. In this work the image quality at high pressures of a FEI Quanta 600 (field emission gun) and a FEI Quanta 200 (thermionic gun) is greatly improved by optimizing the pressure limiting system and the secondary electron (SE) detection system. The scattering of the primary electron beam strongly increases with pressure and thus the image quality vanishes. The key to high-image quality at high pressures is to reduce scattering as far as possible while maintaining ideal operation conditions for the SE-detector. The amount of scattering is reduced by reducing both the additional stagnation gas thickness (aSGT) and the environmental distance (ED). A new aperture holder is presented that significantly reduces the aSGT while maintaining the same field-of-view (FOV) as the original design. With this aperture holder it is also possible to make the aSGT even smaller at the expense of a smaller FOV. A new blade-shaped SE-detector is presented yielding better image quality than usual flat SE-detectors. The electrode of the new SE detector is positioned on the sample table, which allows the SE-detector to operate at ideal conditions regardless of pressure and ED. PMID- 26540291 TI - Determinants and Effects of Voice Disorders among Secondary School Teachers in Peninsular Malaysia Using a Validated Malay Version of VHI-10. AB - OBJECTIVES: To establish the prevalence of voice disorder using the Malay-Voice Handicap Index 10 (Malay-VHI-10) and to study the determinants, quality of life, depression, anxiety and stress associated with voice disorder among secondary school teachers in Peninsular Malaysia. METHODS: This study was divided into two phases. Phase I tested the reliability of the Malay-VHI-10 while Phase II was a cross-sectional study with two-stage sampling. In Phase II, a self-administered questionnaire was used to collect socio-demographic and teaching characteristics, depression, anxiety and stress scale (Malay version of DASS-21); and health related quality of life (Malay version of SF12-v2). Complex sample analysis was conducted using multivariate Poisson regression with robust variance. RESULTS: In Phase I, the Spearman correlation coefficient and Cronbach alpha for total VHI-10 score was 0.72 (p < 0.001) and 0.77 respectively; showing good correlation and internal consistency. The ICCs ranged from 0.65 to 0.78 showing fair to good reliability and demonstrating the subscales to be reliable and stable. A total of 6039 teachers participated in Phase II. They were primarily Malays, females, married, had completed tertiary education and aged between 30 to 50 years. A total of 10.4% (95% CI 7.1, 14.9) of the teachers had voice disorder (VHI-10 score > 11). Compared to Malays, a greater proportion of ethnic Chinese teachers reported voice disorder while ethnic Indian teachers were less likely to report this problem. There was a higher prevalence ratio (PR) of voice disorder among single or divorced/widowed teachers. Teachers with voice disorder were more likely to report higher rates of absenteeism (PR: 1.70, 95% CI 1.33, 2.19), lower quality of life with lower SF12-v2 physical (0.98, 95% CI 0.96, 0.99) and mental (0.97, 95% CI 0.96, 0.98) component summary scales; and higher anxiety levels (1.04, 95% CI 1.02, 1.06). CONCLUSIONS: The Malay-VHI-10 is valid and reliable. Voice disorder was associated with increased absenteeism, marginally associated with reduced health-related quality of life as well as increased anxiety among teachers. PMID- 26540293 TI - Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer. AB - BACKGROUND: Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20 40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical pathologic data. MATERIALS AND METHODS: PIK3CA mutation analysis was performed by using cobas(r) PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. RESULTS: PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. CONCLUSIONS: Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies. PMID- 26540294 TI - Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis. AB - Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490), we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER) stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1) These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10). Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2). Expression quantitative trait loci (eQTL) pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS) arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk. PMID- 26540295 TI - A Case of Urogenital Human Schistosomiasis from a Non-endemic Area. PMID- 26540296 TI - Application of the Repetitive Behavior Scale-Revised--Italian version--in preschoolers with autism spectrum disorder. AB - Restricted repetitive and stereotyped patterns of behavior, interests, and activities (RRB) are mandatory features for a diagnosis of Autism Spectrum Disorder (ASD) according to the Diagnostic and Statistical Manual of mental disorders-fifth edition (DSM-5). Despite the strong diagnostic role of RRB, their expressiveness and their relationship with other clinical/demographic features in ASD is not fully elucidated. The Italian version of the Repetitive Behavior Scale Revised (RBS-R) was applied to a relatively large sample of preschool-aged children with ASD who underwent a comprehensive clinical assessment. The relationship between RRB and sex, age, non-verbal IQ, autism severity, as well as the diagnostic accuracy of the RBS-R were explored. Stereotyped and Ritualistic/Sameness behaviors were the most common RRB in preschoolers with ASD, without widespread differences between males and females. No significant correlations between RRB and chronological age, or non-verbal IQ were detected. The expressiveness of ritualistic/sameness behaviors positively correlated with autism severity, assessed through the Calibrated Severity Score (CSS) derived from the Autism Diagnostic Observation Schedule (ADOS). Receiver Operator Characteristic (ROC) analysis showed high diagnostic accuracy using the Global Rating Score, which represents the judgment of the parents of as the RRB affect the child's life. However, while the Global Rating Score performed well, the remaining subscales did not. This investigation extends the limited research on early pattern and associated features of RRB in young children with ASD. The use of the RBS-R may increase the knowledge of the RRB complexity and variability and in turn improve the diagnostic and therapeutic procedures within the autistic spectrum. PMID- 26540297 TI - Later learning stages in procedural memory are impaired in children with Specific Language Impairment. AB - BACKGROUND: According to the Procedural Deficit Hypothesis (PDH), difficulties in the procedural memory system may contribute to the language difficulties encountered by children with Specific Language Impairment (SLI). Most studies investigating the PDH have used the sequence learning paradigm; however these studies have principally focused on initial sequence learning in a single practice session. AIMS: The present study sought to extend these investigations by assessing the consolidation stage and longer-term retention of implicit sequence-specific knowledge in 42 children with or without SLI. METHODS AND PROCEDURES: Both groups of children completed a serial reaction time task and were tested 24h and one week after practice. OUTCOMES AND RESULTS: Results showed that children with SLI succeeded as well as children with typical development (TD) in the early acquisition stage of the sequence learning task. However, as training blocks progressed, only TD children improved their sequence knowledge while children with SLI did not appear to evolve any more. Moreover, children with SLI showed a lack of the consolidation gains in sequence knowledge displayed by the TD children. CONCLUSIONS AND IMPLICATIONS: Overall, these results were in line with the predictions of the PDH and suggest that later learning stages in procedural memory are impaired in SLI. PMID- 26540299 TI - Generation of a glucose de-repressed mutant of Trichoderma reesei using disparity mutagenesis. AB - We obtained a novel glucose de-repressed mutant of Trichoderma reesei using disparity mutagenesis. A plasmid containing DNA polymerase delta lacking proofreading activity, and AMAI, an autonomously replicating sequence was introduced into T. reesei ATCC66589. The rate of mutation evaluated with 5 fluoroorotic acid resistance was approximately 30-fold higher than that obtained by UV irradiation. The transformants harboring incompetent DNA polymerase delta were then selected on 2-deoxyglucose agar plates with hygromycin B. The pNP lactoside hydrolyzing activities of mutants were 2 to 5-fold higher than the parent in liquid medium containing glucose. Notably, the amino acid sequence of cre1, a key gene involved in glucose repression, was identical in the mutant and parent strains, and further, the cre1 expression levels was not abolished in the mutant. Taken together, these results demonstrate that the strains of T. reesei generated by disparity mutagenesis are glucose de-repressed variants that contain mutations in yet-unidentified factors other than cre1. PMID- 26540298 TI - Proteasome function is not impaired in healthy aging of the lung. AB - Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging. PMID- 26540301 TI - An Assessment of the Effect of Rotenone on Selected Non-Target Aquatic Fauna. AB - Rotenone, a naturally occurring ketone, is widely employed for the management of invasive fish species. The use of rotenone poses serious challenges to conservation practitioners due to its impacts on non-target organisms including amphibians and macroinvertebrates. Using laboratory studies, we investigated the effects of different rotenone concentrations (0, 12.5, 25, 37.5, 50, 100 MUg L-1) on selected invertebrate groups; Aeshnidae, Belostomatids, Decapods, Ephemeroptera, Pulmonata and zooplankton over a period of 18 hours. Based on field observations and body size, we hypothesized that Ephemeropterans and zooplankton would be more susceptible to rotenone than Decapods, Belostomatids and snails. Experimental results supported this hypothesis and mortality and behaviour effects varied considerably between taxa, ranging from no effect (crab Potamonuates sidneyi) to 100% mortality (Daphnia pulex and Paradiaptomus lamellatus). Planktonic invertebrates were particularly sensitive to rotenone even at very low concentrations. Future research should investigate the recovery time of invertebrate communities after the application of rotenone and conduct field assessments assessing the longer term effects of rotenone exposure on the population dynamics of those less sensitive organisms. PMID- 26540300 TI - Two Novel Y-Type High Molecular Weight Glutenin Genes in Chinese Wheat Landraces of the Yangtze-River Region. AB - High molecular weight glutenin subunits (HMW-GSs) are key determinants for the end-use quality of wheat. Chinese wheat landraces are an important resource for exploring novel HMW-GS genes to improve the wheat baking quality. Two novel Glu 1Dy HMW-GSs (designated as 1Dy12.6 and 1Dy12.7) were identified and cloned from two Chinese wheat landraces Huazhong830 and Luosimai. The 1Dy12.6 and 1Dy12.7 subunits were deposited as the NCBInr Acc. No KR262518, and KR262519, respectively. The full open reading frames (ORFs) of 1Dy12.6 and 1Dy12.7 were 2022 bp and 1977 bp, encoding for proteins of 673 and 658 amino acid residues, respectively. Each contains four typical primary regions of HMW-GSs (a signal peptide, N- and C-terminal regions, and a central repetitive region). Their deduced molecular masses (70,165 Da and 68,400 Da) were strikingly consistent with those identified by MALDI-TOF-MS (69,985Da and 68,407 Da). The 1Dy12.6 is the largest 1Dy glutenin subunits cloned in common wheat up to date, containing longer repetitive central domains than other 1Dy encoded proteins. In comparison with the most similar active 1Dy alleles previously reported, the newly discovered alleles contained a total of 20 SNPs and 3 indels. The secondary structure prediction indicated that 1Dy12.6 and 1Dy12.7 have similar proportion of alpha-helix, beta-turn, and beta-bend to those of 1Dy10 (X12929). The phylogenetic analysis illustrated that the x- and y-type subunits of glutenins were well separated, but both 1Dy12.6 and 1Dy12.7 were clustered with the other Glu-1Dy alleles. Our results revealed that the 1Dy12.6 and 1Dy12.7 subunit have potential to strengthen gluten polymer interactions, and are valuable genetic resources for wheat quality improvement. PMID- 26540303 TI - Wet Interface of Benzylhexadecyldimethylammonium Chloride Reverse Micelle Revealed by Excited State Proton Transfer of a Localized Probe. AB - Excited state proton transfer (ESPT) of an anionic photoacid 8-hydroxypyrene 1,3,6-trisulfonic acid (HPTS or pyranine) has been studied inside a cationic reverse micelle (RM), water/benzylhexadecyldimethylammonium chloride (BHDC)/benzene, using steady-state and time-resolved fluorescence spectroscopy. The observed ESPT behavior is found to be remarkably different from the known ESPT trend of HPTS inside anionic AOT and cationic CTAB RMs; the ESPT dynamics approaches that of bulk water at higher w0 (>=10) inside AOT RM while no ESPT was observed for CTAB reverse micelle [ Sedgwick J. Am. Chem. Soc. 2012 , 134 , 11904 - 11907 ]. The ESPT dynamics inside BHDC RM is remarkably slower compared to that of water at all w0 (= [water]/[surfactant]) values and relatively much less sensitive to w0 variation compared to AOT RM. 2D NOESY and fluorescence anisotropy measurements reveal that the probe (HPTS) is embedded inside the positive interface of BHDC RM. Despite its trapped location, HPTS is able to undergo ESPT due to significant penetration of water molecules into the interface. Furthermore, facile ESPT at higher w0 is consistent with higher degree of interface hydration as predicted by a recent MD simulation [ Agazzi Langmuir 2014 , 30 , 9643 - 9653 ]. The study shows that ESPT dynamics inside RM varies not only with the interface charge but also on the nature of the headgroup and solvation. PMID- 26540302 TI - Improvement in Quality of Life after Therapy for Mycobacterium abscessus Group Lung Infection. A Prospective Cohort Study. AB - RATIONALE: Mycobacterium abscessus group lung infection is characterized by low cure rates. Improvement in quality of life may be a reasonable treatment goal. OBJECTIVES: The objective of this study was to evaluate change in quality of life in response to therapy, predictors of improvement in quality of life, and association of quality of life with traditional outcome measures. METHODS: Forty seven patients were treated for Mycobacterium abscessus group lung infection (including one with Mycobacterium chelonae) and were followed prospectively for 2 years between December 2009 and May 2012. St. George's Respiratory Questionnaire (SGRQ) was administered, chest computed tomography (CT) imaging was carried out, and culture data were collected at multiple time points. Predictors of improvement in the SGRQ total score greater than or equal to a minimal clinically important difference (MCID) at 12 months were evaluated. MEASUREMENTS AND MAIN RESULTS: Patients were 85% female and 94% white, with a mean age of 65 years. Nine (20%) had a genetic diagnosis of cystic fibrosis (none F508del homozygous). Coinfection with Mycobacterium avium complex occurred in 28% and Pseudomonas in 26%. Chest CT imaging universally indicated bronchiectasis and nodules; 51% had lung cavities. Treatment included a mean of 17 months of antibiotics, and lung resection in 34%. Seventeen patients with M. avium complex (36%) and one with Mycobacterium kansasii were treated for coinfection. The mean SGRQ total score (SD) at baseline was 35 (20). At all follow-up time points, the mean SGRQ total score (SD) was significantly lower (better) than at baseline: 27 (17) at 3 months, P < 0.01; 27 (19) at 6 months, P < 0.01; 27 (20) at 12 months, P < 0.01; and 30 (22) at 24 months, P = 0.02. At 12 and 24 months, respectively, 60% and 56% had improvement greater than or equal to the MCID in SGRQ total score. Improvement greater than or equal to the MCID at 12 months was positively associated with a history of respiratory exacerbation, isolate susceptible to imipenem-cilastatin, and lung resection surgery, and negatively associated with nodules >4 mm in diameter on chest CT imaging, but these associations were not statistically significant in multivariable analysis. At 24 months, 16 patients (48%) with complete data were culture negative for 1 year and had discontinued M. abscessus group treatment. CONCLUSIONS: Quality of life was a sensitive indicator of treatment response and has the potential to be a useful parameter to guide treatment. PMID- 26540304 TI - Online virtual isocenter based radiation field targeting for high performance small animal microirradiation. AB - Advances in precision microirradiators for small animal radiation oncology studies have provided the framework for novel translational radiobiological studies. Such systems target radiation fields at the scale required for small animal investigations, typically through a combination of on-board computed tomography image guidance and fixed, interchangeable collimators. Robust targeting accuracy of these radiation fields remains challenging, particularly at the millimetre scale field sizes achievable by the majority of microirradiators. Consistent and reproducible targeting accuracy is further hindered as collimators are removed and inserted during a typical experimental workflow. This investigation quantified this targeting uncertainty and developed an online method based on a virtual treatment isocenter to actively ensure high performance targeting accuracy for all radiation field sizes. The results indicated that the two-dimensional field placement uncertainty was as high as 1.16 mm at isocenter, with simulations suggesting this error could be reduced to 0.20 mm using the online correction method. End-to-end targeting analysis of a ball bearing target on radiochromic film sections showed an improved targeting accuracy with the three-dimensional vector targeting error across six different collimators reduced from [Formula: see text] mm (mean +/- SD) to [Formula: see text] mm for an isotropic imaging voxel size of 0.1 mm. PMID- 26540305 TI - Release and re-hook: a novel method with combined use of clips and nylon snare to close a colonic defect after endoscopic mucosal resection. PMID- 26540306 TI - Endoscopic ultrasound-guided fine-needle aspiration of a pulmonary artery malignant thrombus. PMID- 26540307 TI - Squamous metaplasia without atypia. PMID- 26540308 TI - Patients' and physicians' experiences of atrial fibrillation consultations and anticoagulation decision-making: A multi-perspective IPA design. AB - OBJECTIVE: To explore patients' and physicians' experiences of atrial fibrillation (AF) consultations and oral anticoagulation decision-making. DESIGN: Multi-perspective interpretative phenomenological analyses. METHODS: Participants included small homogeneous subgroups: AF patients who accepted (n = 4), refused (n = 4) or discontinued (n = 3) warfarin, and four physician subgroups (n = 4 each group): consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Semi-structured interviews were conducted. Transcripts were analysed using multi-perspective interpretative phenomenological analysis (IPA) analyses to attend to individuals within subgroups and making comparisons within and between groups. RESULTS: Three themes represented patients' experiences: Positioning within the physician-patient dyad, Health-life balance, and Drug myths and fear of stroke. Physicians' accounts generated three themes: Mechanised metaphors and probabilities, Navigating toward the 'right' decision and Negotiating systemic factors. CONCLUSIONS: This multi perspective IPA design facilitated an understanding of the diagnostic consultation and treatment decision-making which foregrounded patients' and physicians' experiences. We drew on Habermas' theory of communicative action to recommend broadening the content within consultations and shifting the focus to patients' life contexts. Interventions including specialist multidisciplinary teams, flexible management in primary care and multifaceted interventions for information provision may enable the creation of an environment that supports genuine patient involvement and participatory decision-making. PMID- 26540310 TI - The Influence of Phonotactic Probability on Nonword Repetition and Fast Mapping in 3-Year-Olds With a History of Expressive Language Delay. AB - PURPOSE: The purpose of this study was to examine the influence of phonotactic probability on sublexical (phonological) and lexical representations in 3-year olds who had a history of being late talkers in comparison with their peers with typical language development. METHOD: Ten 3-year-olds who were late talkers and 10 age-matched typically developing controls completed nonword repetition and fast mapping tasks; stimuli for both experimental procedures differed in phonotactic probability. RESULTS: Both participant groups repeated nonwords containing high phonotactic probability sequences more accurately than nonwords containing low phonotactic probability sequences. Participants with typical language showed an early advantage for fast mapping high phonotactic probability words; children who were late talkers required more exposures to the novel words to show the same advantage for fast mapping high phonotactic probability words. CONCLUSIONS: Children who were late talkers showed similar sensitivities to phonotactic probability in nonword repetition and word learning when compared with their peers with no history of language delay. However, word learning in children who were late talkers appeared to be slower when compared with their peers. PMID- 26540309 TI - The Murine Bladder Supports a Population of Stromal Sca-1+/CD34+/lin- Mesenchymal Stem Cells. AB - Bladder fibrosis is an undesired end point of injury of obstruction and often renders the smooth muscle layer noncompliant. In many cases, the long-term effect of bladder fibrosis is renal failure. Despite our understanding of the progression of this disease, little is known about the cellular mechanisms that lead to a remodeled bladder wall. Resident stem (progenitor) cells have been identified in various organs such as the brain, heart and lung. These cells function normally during organ homeostasis, but become dysregulated after organ injury. Here, we aimed to characterize a mesenchymal progenitor cell population as a first step in understanding its role in bladder fibrosis. Using fluorescence activated cell sorting (FACS), we identified a Sca-1+/ CD34+/ lin- (PECAM-: CD45 : Ter119-) population in the adult murine bladder. These cells were localized to the stromal layer of the adult bladder and appeared by postnatal day 1. Cultured Sca-1+/ CD34+/ lin- bladder cells self-renewed, formed colonies and spontaneously differentiated into cells expressing smooth muscle genes. These cells differentiated into other mesenchymal lineages (chondrocytes, adipocytes and osteocytes) upon culture in induction medium. Both acute and partial obstruction of the bladder reduced expression of CD34 and changed localization of Sca-1 to the urothelium. Partial obstruction resulted in upregulation of fibrosis genes within the Sca-1+/CD34+/lin- population. Our data indicate a resident, mesenchymal stem cell population in the bladder that is altered by bladder obstruction. These findings provide new information about the cellular changes in the bladder that may be associated with bladder fibrosis. PMID- 26540311 TI - Can activated sludge treatments and advanced oxidation processes remove organophosphorus flame retardants? AB - This study aims to determine the occurrence of 10 OPFRs (including chlorinated, nonchlorinated alkyl and aryl compounds) in influent, effluent wastewaters and partitioning into sludge of 5 wastewater treatment plants (WWTP) in Catalonia (Spain). All target OPFRs were detected in the WWTPs influents, and the total concentration ranged from 3.67 ug L(-1) to 150 ug L(-1). During activated sludge treatment, most OPFRs were accumulated in the sludge at concentrations from 35.3 to 9980 ng g(-1) dw. Chlorinated compounds tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP) and tris(2,3-dichloropropyl) phosphate (TDCPP) were not removed by the conventional activated sludge treatment and they were released by the effluents at approximately the same inlet concentration. On the contrary, aryl compounds tris(methylphenyl) phosphate (TMPP) and 2-ethylhexyl diphenyl phosphate (EHDP) together with alkyl tris(2-ethylhexyl) phosphate (TEHP) were not detected in any of the effluents. Advanced oxidation processes (UV/H2O2 and O3) were applied to investigate the degradability of recalcitrant OPFRs in WWTP effluents. Those detected in the effluent sample (TCEP, TCIPP, TDCPP, tributyl phosphate (TNBP), tri-iso-butyl phosphate (TIBP) and tris(2-butoxyethyl) phosphate (TBOEP)) had very low direct UV-C photolysis rates. TBOEP, TNBP and TIBP were degraded by UV/H2O2 and O3. Chlorinated compounds TCEP, TDCPP and TCIPP were the most recalcitrant OPFR to the advanced oxidation processes applied. The study provides information on the partitioning and degradability pathways of OPFR within conventional activated sludge WWTPs. PMID- 26540312 TI - Epithelial Cell-Derived Cytokines Contribute to the Pathophysiology of Eosinophilic Chronic Rhinosinusitis. AB - The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 induce T helper 2 type immune responses. In the present study, we investigate the role of these cytokines in the pathophysiology of eosinophilic chronic rhinosinusitis (ECRS). Nasal tissue specimens from chronic rhinosinusitis patients were assayed for the expression of TSLP, IL-25, IL-33, protease-activated receptor (PAR)-2, and P2Y2 receptor (P2Y2R). Cytokine production in cultured nasal epithelial cells (PNECs) was also examined. The mRNA levels of TSLP and IL-25 and the concentrations of IL-25 and IL-33 increased in PNECs from ECRS patients. Immunohistological staining demonstrated that TSLP, IL 25, and IL-33 were localized in the epithelial cells of nasal polyps, and that their expression was increased in ECRS. The mRNA levels of TSLP and IL-25 correlated with the clinical severity of ECRS, as indicated by the computed tomography score. The TSLP mRNA levels and IL-33 protein concentration correlated with the number of eosinophils in the nasal polyps of patients with ECRS. Airborne allergen-induced cytokine production increased in PNECs of these patients. Expression levels of the PAR-2 and P2Y2R increased in cultured PNECs and nasal polyps from patients with ECRS. The results indicate that increased induction and expression of TSLP, IL-25, and IL-33 from nasal epithelial cells contribute to the pathophysiology of ECRS. PMID- 26540313 TI - The verbal facilitation effect: re-reading person descriptions as a system variable to improve identification performance. AB - When witnesses report a crime, police usually ask for a description of the perpetrator. Several studies suggested that verbalising faces leads to a detriment in identification performance (verbal overshadowing effect [VOE]) but the effect has been difficult to replicate. Here, we sought to reverse the VOE by inducing context reinstatement as a system variable through re-reading one's own description before an identification task. Participants (N = 208) watched a video film and were then dismissed (control group), only described the perpetrator, or described and later re-read their own descriptions before identification in either target-present or target-absent lineups after a 2-day or a 5-week delay. Identification accuracy was significantly higher after re-reading (85.0%) than in the no description control group (62.5%) irrespective of target presence. Data were internally replicated using a second target and corroborated by several small meta-analyses. Identification accuracy was related to description quality. Moreover, there was a tendency towards a verbal facilitation effect (VFE) rather than a VOE. Receiver operating characteristic (ROC) curve analyses confirm that our findings are not due to a shift in response bias but truly reflect improvement of recognition performance. Differences in the ecological validity of study paradigms are discussed. PMID- 26540314 TI - Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study). AB - BACKGROUND: Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression. METHODS: This open label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion. RESULTS: Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A. CONCLUSIONS: These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC. PMID- 26540315 TI - The effect of Health Savings Accounts on group health insurance coverage. AB - This paper presents new empirical evidence on the impact of tax subsidies for Health Savings Accounts (HSAs) on group insurance coverage. HSAs are tax-free health care expenditure savings accounts. Coupled with high deductible health insurance plans (HDHPs), they together represent new health insurance options. The tax advantage of HSAs expands the group health insurance market by making health care more affordable. Using individual level data from the Current Population Survey and exploiting policy variation by state and year from 2004 to 2012, I find that HSA tax subsidies increase small-group coverage by a statistically significant 2.5 percentage points, although not coverage in larger firms. Moreover, if the tax price of HSA contribution decreases by 10 cents, small-group insurance coverage increases by almost 2 percentage points. I also find that for older workers or less-educated workers, HSA subsidies are associated with 2-3 percentage point increase in their group insurance coverage. PMID- 26540317 TI - A graphene meta-interface for enhancing the stretchability of brittle oxide layers. AB - Oxide materials have recently attracted much research attention for applications in flexible and stretchable electronics due to their excellent electrical properties and their compatibility with established silicon semiconductor processes. Their widespread uptake has been hindered, however, by the intrinsic brittleness and low stretchability. Here we investigate the use of a graphene meta-interface to enhance the electromechanical stretchability of fragile oxide layers. Electromechanical tensile tests of indium tin oxide (ITO) layers on polymer substrates were carried out with in situ observations using an optical microscope. It was found that the graphene meta-interface reduced the strain transfer between the ITO layer and the substrate, and this behavior was well described using a shear lag model. The graphene meta-interface provides a novel pathway for realizing flexible and stretchable electronic applications based on oxide layers. PMID- 26540316 TI - Modification of Structural and Luminescence Properties of Graphene Quantum Dots by Gamma Irradiation and Their Application in a Photodynamic Therapy. AB - Herein, the ability of gamma irradiation to enhance the photoluminescence properties of graphene quantum dots (GQDs) was investigated. Different doses of gamma-irradiation were used on GQDs to examine the way in which their structure and optical properties can be affected. The photoluminescence quantum yield was increased six times for the GQDs irradiated with high doses compared to the nonirradiated material. Both photoluminescence lifetime and values of optical band gap were increased with the dose of applied gamma irradiation. In addition, the exploitation of the gamma-irradiated GQDs as photosensitizers was examined by monitoring the production of singlet oxygen under UV illumination. The main outcome was that the GQDs irradiated at lower doses act as better photoproducers than the ones irradiated at higher doses. These results corroborate that the structural changes caused by gamma irradiation have a direct impact on GQD ability to produce singlet oxygen and their photostability under prolonged UV illumination. This makes low-dose irradiated GQDs promising candidates for photodynamic therapy. PMID- 26540319 TI - To err is human, but.... PMID- 26540318 TI - Mitigation of Tumor-Associated Fibroblast-Facilitated Head and Neck Cancer Progression With Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab. AB - IMPORTANCE: Ficlatuzumab can be used to treat head and neck squamous cell carcinoma (HNSCC) by inhibiting c-Met receptor-mediated cell proliferation, migration, and invasion. OBJECTIVE: To understand the effect of ficlatuzumab on HNSCC proliferation, migration, and invasion. DESIGN, SETTING, AND PARTICIPANTS: The effects of ficlatuzumab on HNSCC proliferation, invasion, and migration were tested. Mitigation of c-Met and downstream signaling was assessed by immunoblotting. The tumor microenvironment has emerged as an important factor in HNSCC tumor progression. The most abundant stromal cells in HNSCC tumor microenvironment are tumor-associated fibroblasts (TAFs). We previously reported that TAFs facilitate HNSCC growth and metastasis. Furthermore, activation of the c-Met tyrosine kinase receptor by TAF-secreted hepatocyte growth factor (HGF) facilitates tumor invasion. Ficlatuzumab is a humanized monoclonal antibody that sequesters HGF, preventing it from binding to and activating c-Met. We hypothesized that targeting the c-Met pathway with ficlatuzumab will mitigate TAF mediated HNSCC proliferation, migration, and invasion. Representative HNSCC cell lines HN5, UM-SCC-1, and OSC-19 were used in these studies. EXPOSURES FOR OBSERVATIONAL STUDIES: The HNSCC cell lines were treated with ficlatuzumab, 0 to 100 ug/mL, for 24 to 72 hours. MAIN OUTCOMES AND MEASURES: Ficlatuzumab inhibited HNSCC progression through c-Met and mitogen-activated protein kinase (MAPK) signaling pathway. RESULTS: Ficlatuzumab significantly reduced TAF-facilitated HNSCC cell proliferation (HN5, P < .001; UM-SCC-1, P < .001), migration (HN5, P = .002; UM-SCC-1, P = .01; and OSC-19, P = .04), and invasion (HN5, P = .047; UM SCC-1, P = .03; and OSC-19, P = .04) through a 3-dimensional peptide-based hydrogel (PGmatrix). In addition, ficlatuzumab also inhibited the phosphorylation of c-Met at Tyr1234/1235 and p44/42 MAPK in HNSCC cells exposed to recombinant HGF. CONCLUSIONS AND RELEVANCE: We demonstrate that neutralizing TAF-derived HGF with ficlatuzumab effectively mitigates c-Met signaling and decreases HNSCC proliferation, migration, and invasion. Thus, ficlatuzumab effectively mitigates stromal influences on HNSCC progression. PMID- 26540320 TI - Should all patients with significant proteinuria take a renin-angiotensin inhibitor? PMID- 26540321 TI - Stellate ulceration in a nonuremic patient. PMID- 26540322 TI - The color purple. PMID- 26540323 TI - Noncosmetic uses of botulinum toxin in otolaryngology. AB - Botulinum toxin has several noncosmetic uses in otolaryngology. It is the primary treatment for spasmodic dysphonia and may be effective in select patients who have essential tremor of the voice. It may also be used to treat swallowing difficulties caused by cricopharyngeal dysfunction. PMID- 26540324 TI - Pancreas transplant for diabetes mellitus. AB - Pancreas transplant is an option for patients with type 1 diabetes and for some patients with type 2 diabetes and advanced diabetic kidney disease. The procedure has a high success rate, and performing it earlier in the course of diabetes could help prevent or reverse the long-term complications of diabetes. PMID- 26540325 TI - An elderly woman with 'heart failure': cognitive biases and diagnostic error. AB - Errors in diagnosis can arise from the clinician's cognitive biases as well as from problems in the healthcare system. Here the authors review a case with a bad outcome to analyze what went wrong and why. PMID- 26540326 TI - Women's health 2015: an update for the internist. AB - The field of women's health is varied and dynamic. Major studies in 2014 and the first half of 2015 suggest that selective serotonin reuptake inhibitors are not strongly associated with congenital heart defects, that paroxetine 7.5 mg is effective for treating menopausal symptoms, and that women with heart failure may benefit more from cardiac resynchronization therapy than men. PMID- 26540327 TI - Recreational cannabis use: pleasures and pitfalls. AB - Cannabis is widely used for a variety of reasons, and its changing legal status may foster more new users. Although the acute clinical effects of cannabis are generally benign, clinicians should be aware of health complications and testing limitations. PMID- 26540328 TI - Common infectious complications of liver transplant. AB - Major improvements in the care of liver transplant recipients have mitigated but not eliminated the risk of potentially life-threatening infectious complications. This review provides general information about risk factors, prophylactic strategies, diagnostic workup, and therapy for some of the most commonly encountered infections after liver transplant. PMID- 26540329 TI - Robust Manipulation of Magnetism in Dilute Magnetic Semiconductor (Ga,Mn)As by Organic Molecules. AB - Surface adsorption of organic molecules provides a new method for the robust manipulation of ferromagnetism in (Ga,Mn)As. Electron acceptor and donor molecules yield significant enhancement and suppression, respectively, of ferromagnetism with modulation of the Curie temperature spanning 36 K. Dip-pen nanolithography is employed to directly pattern monolayers on (Ga,Mn)As, which is presented as a novel pathway toward producing magnetic nanostructures. PMID- 26540330 TI - Mechanistic Insights into the H2S-Mediated Reduction of Aryl Azides Commonly Used in H2S Detection. AB - Hydrogen sulfide (H2S) is an important biological mediator and has been at the center of a rapidly expanding field focused on understanding the biogenesis and action of H2S as well as other sulfur-related species. Concomitant with this expansion has been the development of new chemical tools for H2S research. The use of H2S-selective fluorescent probes that function by H2S-mediated reduction of fluorogenic aryl azides has emerged as one of the most common methods for H2S detection. Despite this prevalence, the mechanism of this important reaction remains under-scrutinized. Here we present a combined experimental and computational investigation of this mechanism. We establish that HS(-), rather than diprotic H2S, is the active species required for aryl azide reduction. The hydrosulfide anion functions as a one-electron reductant, resulting in the formation of polysulfide anions, such as HS2(-), which were confirmed and trapped as organic polysulfides by benzyl chloride. The overall reaction is first-order in both azide and HS(-) under the investigated experimental conditions with DeltaS(?) = -14(2) eu and DeltaH(?) = 13.8(5) kcal/mol in buffered aqueous solution. By using NBu4SH as the sulfide source, we were able to observe a reaction intermediate (lambda(max) = 473 nm), which we attribute to formation of an anionic azidothiol intermediate. Our mechanistic investigations support that this intermediate is attacked by HS(-) in the rate-limiting step of the reduction reaction. Complementing our experimental mechanistic investigations, we also performed DFT calculations at the B3LYP/6-31G(d,p), B3LYP/6-311++G(d,p), M06/TZVP, and M06/def2-TZVPD levels of theory applying the IEF-PCM water and MeCN solvation models, all of which support the experimentally determined reaction mechanism and provide cohesive mechanistic insights into H2S-mediated aryl azide reduction. PMID- 26540331 TI - HTP-OligoDesigner: An Online Primer Design Tool for High-Throughput Gene Cloning and Site-Directed Mutagenesis. AB - Following burgeoning genomic and transcriptomic sequencing data, biochemical and molecular biology groups worldwide are implementing high-throughput cloning and mutagenesis facilities in order to obtain a large number of soluble proteins for structural and functional characterization. Since manual primer design can be a time-consuming and error-generating step, particularly when working with hundreds of targets, the automation of primer design process becomes highly desirable. HTP OligoDesigner was created to provide the scientific community with a simple and intuitive online primer design tool for both laboratory-scale and high-throughput projects of sequence-independent gene cloning and site-directed mutagenesis and a Tm calculator for quick queries. PMID- 26540333 TI - Brain, Craniofacial, and Dental Lesions of a Free-ranging Gray Wolf (Canis lupus) Implicated in a Human Attack in Minnesota, USA. AB - We describe significant brain, craniofacial, and dental lesions in a free-ranging wolf (Canis lupus) involved in a human attack. On postmortem examination, the wolf presented asymmetric atrophy and bone remodeling affecting the mandible, incisive, maxilla, lacrimal, palatine, frontal, and ethmoid bones. There was an asymmetrical skeletal malocclusion and dental abnormalities including rotated, malpositioned, partially erupted teeth, and an odontogenic cyst associated with an unerupted canine tooth. Brain changes were bilateral loss and atrophy of extensive cortex regions including olfactory bulb, peduncles, and tract, and the frontal lobe. We highlight the relevance of a thorough postmortem examination of wildlife to elucidate disease-based abnormal behavior as the reason for human animal conflict. PMID- 26540335 TI - Anti-Brucella Antibodies in Moose (Alces alces gigas), Muskoxen (Ovibos moschatus), and Plains Bison (Bison bison bison) in Alaska, USA. AB - We used an indirect enzyme-linked immunosorbent assay (iELISA) and the rose bengal test (RBT) to test for anti-Brucella antibodies in moose (Alces alces gigas), muskoxen (Ovibos moschatus), and plains bison (Bison bison bison) from various game management units (GMUs) in Alaska, US, sampled from 1982 to 2010. A portion of the sera had previously been tested with the standard plate test (SPT), the buffered Brucella antigen (BBA) card test, and the card test (CARD). No antibody-positive plains bison were identified. Anti-Brucella antibodies were detected in moose (iELISA, n=4/87; RBT, n=4/87; SPT, n=4/5; BBA, n=4/4) from GMU 23 captured in 1992, 1993, and 1995 and in muskoxen (iELISA, n=4/52; RBT, n=4/52; CARD, n=4/35) from GMUs 26A and 26B captured in 2004, 2006, and 2007. A negative effect of infection on the health of individuals of these species is probable. The presence of antibody-positive animals from 1992 to 2007 suggests presence of brucellae over time. The antibody-positive animals were found in northern Alaska, an area with a historically higher prevalence of Brucella-positive caribou, and a spillover of Brucella suis biovar 4 from caribou may have occurred. Brucella suis biovar 4 causes human brucellosis, and transmission from consumption of moose and muskoxen is possible. PMID- 26540334 TI - Antibodies to Rickettsia spp. and Borrelia burgdorferi in Spanish Wild Red Foxes (Vulpes vulpes). AB - We examined 314 red foxes (Vulpes vulpes) from the province of Soria, Spain, for Rickettsia typhi, Rickettsia slovaca, and Borrelia burgdorferi infection. Immunofluorescence assays showed 1.9% had antibodies to R. typhi, 6.7% had antibodies to R. slovaca, and 8.3% had antibodies to B. burgdorferi. Serostatus was not correlated with sex or age. Because red foxes can be infected by Rickettsiae and B. burgdorferi, presence of red foxes may be and indicator for the presence of these pathogens. PMID- 26540336 TI - West Nile Virus in Resident Birds from Yucatan, Mexico. AB - West Nile virus (WNV) in the Americas is thought to be transported at large spatial scales by migratory birds and locally spread and amplified by resident birds. Local processes, including interspecific interactions and dominance of passerine species recognized as competent reservoirs, may boost infection and maintain endemic cycles. Change in species composition has been recognized as an important driver for infection dynamics. Due to migration and changes in species diversity and composition in wintering grounds, changes in infection prevalence are expected. To these changes, we used PCR to estimate the prevalence of WNV in wild resident birds during the dry and rainy seasons of 2012 in Yucatan, Mexico. Serum samples were obtained from 104 wild birds, belonging to six orders and 35 species. We detected WNV in 14 resident birds, representing 11 species and three orders. Prevalences by order was Passeriformes (27%), Columbiformes (6%), and Piciformes (33%). Resident birds positive to WNV from Yucatan may be indicative of local virus circulation and evidence of past virus transmission activity. PMID- 26540337 TI - Mother's Milk as a Source of Enterobacter cloacae Sepsis in a Preterm Infant. PMID- 26540338 TI - Trisubstituted Thieno[3,2-b]pyrrole 5-Carboxamides as Potent Inhibitors of Alphaviruses. AB - Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus and is transmitted to humans by Aedes mosquitoes. Despite the re-emergence of CHIKV as an epidemic threat, there is no approved effective antiviral treatment currently available for CHIKV. Herein, we report the synthesis and structure-activity relationship studies of a class of thieno[3,2-b]pyrroles and the discovery of a trisubstituted thieno[3,2-b]pyrrole 5-carboxamide 15c that exhibits potent inhibitory activity against in vitro CHIKV infection. Compound 15c displayed low micromolar activity (EC50 value of ca. 2 MUM) and limited cytotoxic liability (CC50 > 100 MUM) therefore furnishing a selectivity index of greater than 32. Notably, 15c not only controlled viral RNA production, but efficiently inhibited the expression of CHIKV nsP1, nsP3, capsid, and E2 proteins at a concentration as low as 2.5 MUM. More importantly, 15c also demonstrated broad spectrum antiviral activity against other clinically important alphaviruses such as O'nyong-nyong virus and Sindbis virus. PMID- 26540340 TI - Effect of methylation on the side-chain pKa value of arginine. AB - Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 +/- 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition. PMID- 26540339 TI - Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats. AB - Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists. PMID- 26540341 TI - Dynamics and Diffusion Mechanism of Low-Density Liquid Silicon. AB - A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid-liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using the classical Stillinger-Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid liquid phase transition such as carbon and germanium. PMID- 26540342 TI - An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to mesenchymal transition (EMT) in colorectal cancer. AB - In human cancer, high telomerase expression is correlated with tumor aggressiveness and metastatic potential. Telomerase activation occurs through telomerase reverse transcriptase (hTERT) induction, which contributes to malignant transformation by stabilizing telomeres. Previous studies have shown that hTERT can promote tumor invasion and metastasis of gastric cancer, liver cancer and esophageal cancer. Epithelial-to-mesenchymal transition (EMT), a requirement for tumor invasion and metastasis, plays a key role in cancer progression. Although hTERT promotes EMT through Wnt signaling in several cancers, it is unknown if other signaling pathways are involved. In the present study, we found that hTERT and ZEB1 form a complex, which directly binds to the E cadherin promoter, and then inhibits E-cadherin expression and promots EMT in colorectal cancer cells. hTERT overexpression in HCT116 and SW480 cells could induce E-cadherin down-regulation. However, E-cadherin expression was recovered when ZEB1 function was impaired even during hTERT overexpression. Taken together, our findings suggest that hTERT can promote cancer metastasis by stimulating EMT through the ZEB1 pathway and therefore inhibiting them may prevent cancer progression. PMID- 26540343 TI - LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway. AB - Hepatocellular carcinoma (HCC) is well known as the sixth most common malignant tumor and the third leading cause of cancer-related deaths globally. LINC00152 was documented as an important long non-coding RNA (lncRNA) involved in the pathogenesis of gastric cancer; however, the detailed mechanism of action of LINC00152 remains unknown. Here, based on the increased level of LINC00152 in HCC tissues, we found that LINC00152 could promote cell proliferation in vitro and tumor growth in vivo. Furthermore, microarray-based analysis indicated that LINC00152 could activate the mechanistic target of rapamycin(mTOR) pathway by binding to the promoter of EpCAM through a cis-regulation, as confirmed by Gal4 lambdaN/BoxB reporter system. Thus, LINC00152 might be involved in the oncogenesis of HCC by activating the mTOR signaling pathway and might be a novel index for clinical diagnosis in the future. PMID- 26540345 TI - Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E. AB - Cancer-testis antigen MAGE-C2 is normally expressed in testis but aberrantly expressed in various kinds of tumors. Its functions in tumor cells are mostly unknown. Here, we show that MAGE-C2 binds directly to the RING domain protein Rbx1, and participates in Skp1-Cullin1-F box protein (SCF) complex. Furthermore, MAGE-C2 can inhibit the E3 ubiquitin ligase activity of SCF complex. Ablation of endogenous MAGE-C2 decreases the level of cyclin E and accelerates cyclin E turnover by inhibiting ubiquitin-mediated proteasome degradation. Overexpression of MAGE-C2 increases the level of cyclin E and promotes G1-S transition and cell proliferation, and the results are further confirmed by knockdown of MAGE-C2. Overall, the study indicates that MAGE-C2 is involved in SCF complex and increases the stability of cyclin E in tumor cells. PMID- 26540344 TI - Ell3 stabilizes p53 following CDDP treatment via its effects on ubiquitin dependent and -independent proteasomal degradation pathways in breast cancer cells. AB - The tumor suppressor protein p53 is unstable in quiescent cells and undergoes proteosomal degradation. Under conditions of cellular stress, p53 is rapidly stabilized by post-translational modification, thereby escaping degradation and translocating to the nucleus where it activates genes related to cell cycle arrest or apoptosis. Here, we report that the transcription elongation factor Ell3 sensitizes luminal type-cancer cell line, MCF7, which have wild-type p53, to the chemotherapeutic agent cis-diamminedichloroplatinum(II) (CDDP) by stabilizing p53. Overexpression of Ell3 in MCF7 cells suppressed the MDM2-mediated ubiquitin dependent degradation pathway. In addition, Ell3 promoted binding of p53 to NADH quinone oxidoreductase 1, which is linked to the ubiquitin-independent degradation of p53. We found that Ell3 activates interleukin-20 (IL20) expression, which is linked to the ERK1/2 signaling pathway. Chemical inhibition of ERK1/2 signaling or molecular suppression of IL20 revealed that the ERK1/2 signaling pathway and IL20 are the main causes of p53 stabilization in Ell3 overexpressing MCF7 cells. These findings suggest that the ERK1/2 pathway can be targeted in the rational development of therapies to induce chemosensitization of breast cancer cells. PMID- 26540346 TI - Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model. AB - Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma. PMID- 26540347 TI - Knock out CD44 in reprogrammed liver cancer cell C3A increases CSCs stemness and promotes differentiation. AB - CD44 is a widely known cancer stem cells marker in various cancers and validated to function in tumor growth, survival and tumor metastasis. In this study, we first established C3A-derived liver cancer stem cells by OSKM method [OCT4, SOX2, KLF4, and c-MYC], termed C3A-induced cancer stem cells (C3A-iCSCs) which acquired self-renewal and stemness abilities. Then we found CD44 was positive in C3A-iCSCs and mainly located in cell nuclear. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) results showed nuclear CD44 combined promoter regions of c-MYC and SOX2. These results suggested that CD44 participated in C3A-iCSCs transcriptional regulation. To explore CD44 overall influence in liver cancer stem cells, CD44 was knocked out in C3A-iCSCs using CRISPR/Cas9 technology. Our results showed a dramatic increase in the expression of stem cell markers OCT4, SOX2 and NANOG in CD44- C3A-iCSCs compared with that in CD44+ C3A-iCSCs. Tumor derived from CD44- C3A-iCSCs also displayed well-differentiated tumor cells compared to CD44+ C3A-iCSCs, which suggested CD44- C3A-iCSCs derived tumor cells exhibited lower malignant degree. Our data indicated nuclear CD44 in liver cancer stem cells is responsible for the poorly differentiated highly malignant tumor cells by maintenance of low stemness state. PMID- 26540349 TI - Single-molecule perspectives on helicase mechanisms and functions. AB - Helicases are a diverse group of molecular motors that utilize energy derived from the hydrolysis of nucleoside triphosphates (NTPs) to unwind and translocate along nucleic acids. These enzymes play critical roles in nearly all aspects of nucleic acid metabolism, and consequently, a detailed understanding of helicase mechanisms at the molecular level is essential. Over the past few decades, single molecule techniques, such as optical tweezers, magnetic tweezers, laminar flow, fluorescence resonance energy transfer (FRET), and DNA curtains, have proved to be powerful tools to investigate the functional properties of both DNA and RNA helicases. These approaches allow researchers to manipulate single helicase molecules, perturb their free energy landscape to probe the chemo-mechanical activities of these motors, and to detect the conformational changes of helicases during unwinding. Furthermore, these techniques also provide the capability to distinguish helicase heterogeneity and monitor helicase motion at nanometer spatial and millisecond temporal resolutions, ultimately providing new insights into the mechanisms that could not be resolved by ensemble assays. This review outlines the single-molecule techniques that have been utilized for measurements of helicase activities and discusses helicase mechanisms with a focus on functional and mechanistic insights revealed through single-molecule investigations in the past five years. PMID- 26540348 TI - LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation. AB - The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase alphaTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy. PMID- 26540350 TI - Soybean agglutinin-conjugated silver nanoparticles nanocarriers in the treatment of breast cancer cells. AB - Silver nanoparticles (AgNPs) induce diverse cell-death mechanisms, similar to those promoted by anticancer chemotherapeutics; however, they have not been tested in vivo because their action is not limited to cancer cells. Therefore, in vivo evaluations of their effectiveness should be developed with targeting systems. Breast cancer shows changes in the sugar expression patterns on cell surfaces, related to cancer progression and metastases; those changes have been identified previously by the specific binding of soybean agglutinin (SBA). Here is proposed the use of SBA to target the AgNP activity in breast cancer. For that, the present work reports the synthesis of AgNPs (3.89 +/- 0.90 nm) through the polyol method, the generation of AgNP nanocarriers, and the bioconjugation protocol of the nanocarrier with SBA. The free AgNPs, the AgNP nanocarriers, and the SBA-bioconjugated AgNP nanocarriers were tested for cytotoxicity in breast cancerous (MDA-MB-231and MCF7) and non cancerous (MCF 10A) cells, using the MTT assay. AgNPs demonstrated cytotoxic activity in vitro, the non cancerous cells (MCF 10A) being more sensible than the cancerous cells (MDA-MB-231 and MCF7) showing LD(50) values of 128, 205, and 319 MUM Ag, respectively; the nanoencapsulation decreased the cytotoxic effect of AgNPs in non cancerous cells, maintaining or increasing the effect on the cancer-derived cells, whereas the SBA bioconjugation allowed AgNP cytotoxic activity with a similar behavior to the nanocarriers. Future experiments need to be developed to evaluate the targeting effect of the SBA-bioconjugated AgNP nanocarriers to study their functionality in vivo. PMID- 26540351 TI - Surgical Decompression of Arachnoid Cysts Leads to Improved Quality of Life: A Prospective Study. AB - BACKGROUND: There is no previous prospective study on the outcome of surgical decompression of intracranial arachnoid cysts (AC). OBJECTIVE: To investigate if surgical fenestration for AC leads to change in patients' health-related quality of life. METHODS: Prospective study including 76 adult patients operated for AC. Patients responded to Short Form-36 and Glasgow Benefit Inventory quality of life questionnaires, and to visual analogue scales, assessing headache and dizziness pre- and postoperatively. Patient scores were compared with those of a large sample of healthy individuals. RESULTS: Preoperatively, 84.2% of the patients experienced headache and 70.1% dizziness. Mean pre- versus postoperative Visual Analogue Scale scores for headache and dizziness dropped from 45.6 to 25.7 and from 35.2 to 12.2, respectively. Preoperative Short Form-36 scores were significantly below age norms in all subscales, but improved after surgery into normal range in 7 out of 8 subscales for middle-aged and older patients. Younger patients' scores remained lower than age norm in 6 out of 8 subscales. A significant postoperative improvement was seen in 3 out of 4 Glasgow Benefit Inventory subscales. Improvement in headache and/or dizziness, but not preoperative cyst size or reduction in cyst volume, correlated with improvement in 6 out of 8 Short Form-36 subscales and 3 out of 4 Glasgow Benefit Inventory subscales. Only 1 patient experienced a severe complication causing permanent invalidity. CONCLUSION: Surgery for AC can be performed with a fairly low risk of complications and yields significant improvement in quality of life correlated to postoperative improvement in headache and dizziness. These findings may justify a more liberal approach to surgical treatment for AC. PMID- 26540353 TI - Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents. AB - BACKGROUND: Triolein emulsion infusion into the carotid artery has been reported to induce temporary and reversible opening of the blood-brain barrier by increasing vascular permeability. OBJECTIVE: To evaluate the effect of triolein emulsion infusion on brain permeance by anticancer agents. METHODS: In the doxorubicin study. 2.4 mg/kg doxorubicin was injected immediately after triolein emulsion (1%, 1.5%, and 2%) infusion into rabbit carotid arteries. Two hours later, bilateral hemispheres and eyeballs were harvested, and doxorubicin concentrations were measured fluorometrically. Doxorubicin ratios of ipsilateral/contralateral hemispheres were compared with those of doxorubicin controls by use of the Kruskal-Wallis test followed by the Dunn test. In the cisplatin study, 10 mg/kg cisplatin was injected immediately after 2% triolein emulsion infusion into rat carotid arteries. Ipsilateral hemispheres were harvested 2, 6, 12, 24, and 36 hours after treatment. Time-dependent cisplatin concentrations were determined by liquid chromatography/electrospray ionization tandem mass spectrometry/mass spectrometry. RESULTS: Doxorubicin concentrations were significantly higher in ipsilateral hemispheres and eyeballs in all 3 triolein treatment groups than in doxorubicin controls. In the cisplatin study, cisplatin concentrations in the ipsilateral hemispheres peaked at 6 hours after infusion of cisplatin. CONCLUSION: Brain permeance to anticancer agents was increased by triolein emulsion infusion, which suggests that triolein infusion might be a useful adjuvant treatment for brain tumors. PMID- 26540357 TI - Lower Risk of Intracranial Arteriovenous Malformation Hemorrhage in Patients With Hereditary Hemorrhagic Telangiectasia. AB - BACKGROUND: Patients diagnosed with hereditary hemorrhagic telangiectasia (HHT) are at risk of developing intracranial arteriovenous malformations (AVM). However, the clinical manifestations and natural history of HHT-related AVMs remain unclear due to the rarity of these lesions. OBJECTIVE: To clarify the clinical characteristics and hemorrhagic risk in HHT-related AVMs. METHODS: We performed a retrospective review of all patients diagnosed with both HHT and intracranial AVMs who were evaluated at our institution from 1990 to 2013. Patients with missing data or lost to follow-up were excluded. Baseline characteristics and subsequent hemorrhagic risk were evaluated. RESULTS: In an AVM database of 531 patients with 542 AVMs, a total of 12 HHT patients (2.3%) with 23 AVMs were found. Mean age at diagnosis was 36.5 years, with 41.7% male. Compared to patients with sporadic AVMs, patients with HHT were less likely to present with ruptured AVM (P = .04), headaches (P = .02), and seizures (P = .02), and presented with better modified Rankin scores (P < .01). HHT-related AVMs were smaller in size (P < .01), of lower Spetzler-Martin grade (P = .01), and had less temporal lobe involvement (P = .02) compared to sporadic AVMs. Six HHT patients (50.0%) were found with multiple intracranial AVMs. One hemorrhage was found during an observation period of 149.6 patient-years and 297.5 lesion-years, translating to 1.3% per patient per year or 0.7% per AVM per year. CONCLUSION: HHT-related AVMs are smaller in size with lower Spetzler-Martin grade and less temporal lobe involvement than sporadic AVMs. Patients with HHT frequently present with multiple intracranial AVMs. Conservative management is generally recommended due to lesion multiplicity and relatively low hemorrhagic risk. PMID- 26540358 TI - Commentary: Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord. PMID- 26540359 TI - Asymptomatic Intraocular Mass. PMID- 26540360 TI - Radiological mapping of Kelantan, Malaysia, using terrestrial radiation dose rate. AB - Measurements of the environmental terrestrial gamma radiation dose rate (TGRD) in each district of Kelantan state, Malaysia, were carried out using a portable hand held radiation survey meter and global positioning system. The measurements were done based on geology and soil types of the area. The mean TGRD was found to be 209 nGy h(-1). Few areas of relatively enhanced activity were observed in Pasir Mas, Tanah Merah and Jeli districts, which have a mean TGRD between 300 and 500 nGy h(-1). An isodose map of the area was produced using ArcGIS software version 9.3. PMID- 26540361 TI - The complete mitochondrial genome of Triplophysa sp. (Teleostei: Cypriniformes: Balitoridae). AB - The complete mitochondrial genome sequence of balitorid fish, Triplophysa sp., which was from Qinling mountains, central China, has been sequenced by the long polymerase chain with primer walking method. The mitochondrial genome of Triplophysa sp. is similar to those of the typical vertebrates, 16 570 bp in length, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region (D-loop). Most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes which are encoded on the light strand. The overall base composition of the heavy strand of the Triplophysa sp. mitogenome is A: 28.0%, T: 28.0%, C: 25.8%, and G: 18.2%. Combined with the complete mitogenome sequences of other 15 balitorids, the topology demonstrated that Triplophysa sp. has a close relationship with the cluster consisting of Triplophysa yarkandensis, Triplophysa siluroides, and Triplophysa robusta with high support values. The genera Triplophysa and Barbatula formed a sister-group relationship. Further investigations with more Triplophysa species included need to be performed to better understand the evolutionary history of this intriguing genus. PMID- 26540362 TI - Comparative Microstrain Study of Internal Hexagon and Plateau Design of Short Implants Under Vertical Loading. AB - PURPOSE: To quantify microstrain development during axial loading using strain gauge analysis for short implants, varying the type of fixture-abutment joint and thread design. MATERIALS AND METHODS: An internal hexagon implant (4 * 8 mm) and a plateau design implant (4 * 8 mm) were embedded on the center of 10 polyurethane blocks with dimensions of 190 * 30 * 12 mm. The respective abutments were screwed onto the implants. Four strain gauges (SGs) were bonded onto the surface of each block, and 4 vertical SGs were bonded onto the side of each block. Axial load of 30 kgf was applied for 10 seconds in the center of each implant. RESULTS: The data were analyzed statistically by analysis of variance for repeated measures and Tukey test (P < 0.05). The interaction between implant and region factors have been statistically significant (P = 0.0259). Tukey test revealed a difference on plateau's horizontal region. The cervical region presented higher microstrain values, when compared with the medium and apical regions of the implants. CONCLUSION: Within the purpose of the study, the type of fixture-abutment joint is a relevant factor to affect the amount of stress/strain in bone simulation. The microstrain development was concentrated on the cervical region of the implant. PMID- 26540364 TI - The Onward March of Implant-Related Technology. PMID- 26540363 TI - Effect of Microthread Design on Marginal Bone Level Around Dental Implants Placed in Fresh Extraction Sockets. AB - PURPOSE: This study was designed to compare radiographically the effect of microthread on the coronal portion of the fixture on marginal bone level (MBL) around immediately placed dental implants in human subjects. MATERIAL AND METHODS: Forty-one roughened surface screw type Dentium oral implants (Dentium) were inserted in fresh extraction sockets of the anterior segment of maxilla of 30 patients. The implants were selected randomly using either microthread design on coronal portion of the fixture (Implantium) (test group) or without microthread thread design (Superline) (control group). MBL was measured using digital subtraction radiography technique after 3, 6, and 12 months. RESULTS: At month 3, the microthread groups have been associated with more marginal bone loss than the control group (P = 0.04). At months 6 and 12, both groups had comparable bone levels (P = 0.21). CONCLUSION: The microthread design of the implant collar could not have a positive effect in maintaining the MBL around implants placed in fresh extraction socket in anterior maxilla. PMID- 26540365 TI - Effects of Hard Thin-Film Coatings on Adhesion of Early Colonizer Bacteria Over Titanium Surfaces. AB - PURPOSE: The purpose of this in vitro study was to evaluate the effect of diamond like carbon (DLC) and titanium (Ti) nitride coatings over Ti surfaces on the adhesion of early colonizer bacteria. MATERIALS AND METHODS: Specimens were divided into 3 groups (n = 10) according to different surface modifications: titanium nitride (TiN)-coated Ti discs (experimental group 1), DLC-coated Ti discs (experimental group 2), and uncoated polished Ti discs (control group). Discs were incubated in bacterial cell suspension (Streptococcus mutans and Streptococcus sanguis) for 1 hour, and the single colonies formed by adhering bacteria were counted by fluorescence microscopy. Surface roughness and topography were examined by atomic force microscopy. RESULTS: The surface roughness of DLC was lower than TiN coating and the control group. Statistically significant reduction of the number of adherent bacteria was observed on DLC coated surfaces. CONCLUSIONS: DLC coating over Ti surfaces strongly inhibits the adhesion of early colonizer oral bacteria. PMID- 26540366 TI - Oligomer Molecules for Efficient Organic Photovoltaics. AB - Solar cells, a renewable, clean energy technology that efficiently converts sunlight into electricity, are a promising long-term solution for energy and environmental problems caused by a mass of production and the use of fossil fuels. Solution-processed organic solar cells (OSCs) have attracted much attention in the past few years because of several advantages, including easy fabrication, low cost, lightweight, and flexibility. Now, OSCs exhibit power conversion efficiencies (PCEs) of over 10%. In the early stage of OSCs, vapor deposited organic dye materials were first used in bilayer heterojunction devices in the 1980s, and then, solution-processed polymers were introduced in bulk heterojunction (BHJ) devices. Relative to polymers, vapor-deposited small molecules offer potential advantages, such as a defined molecular structure, definite molecular weight, easy purification, mass-scale production, and good batch-to-batch reproducibility. However, the limited solubility and high crystallinity of vapor-deposited small molecules are unfavorable for use in solution-processed BHJ OSCs. Conversely, polymers have good solution-processing and film-forming properties and are easily processed into flexible devices, whereas their polydispersity of molecular weights and difficulty in purification results in batch to batch variation, which may hamper performance reproducibility and commercialization. Oligomer molecules (OMs) are monodisperse big molecules with intermediate molecular weights (generally in the thousands), and their sizes are between those of small molecules (generally with molecular weights <1000) and polymers (generally with molecular weights >10000). OMs not only overcome shortcomings of both vapor-deposited small molecules and solution-processed polymers, but also combine their advantages, such as defined molecular structure, definite molecular weight, easy purification, mass-scale production, good batch to-batch reproducibility, good solution processability, and film-forming properties. Therefore, OMs are a good choice for solution-processed reproducible OSCs toward scalable commercialized applications. Considerable efforts have been dedicated to developing new OM electron donors and electron acceptors for OSCs. So far, the highest PCEs of solution-processed OSCs based on OM donors and acceptors are 9-10% and 6-7%, respectively. OM materials have become promising alternatives to polymer and/or fullerene materials for efficient and stable OSCs. In this Account, we present a brief survey of the recent developments in solution processable OM electron donors and acceptors and their application in OSCs. Rational design of OMs with star- and linear-shaped structures based on triphenylamine, benzodithiophene, and indacenodithiophene units and their impacts on device performance are discussed. Structure-property relationships are also proposed. Furthermore, the remaining challenges and the key research directions in the near future are also addressed. In the next years, an interdisciplinary approach involving novel OM materials, especially electron acceptor materials, accurate morphology optimization, and advanced device technologies will probably bring high-efficiency and stable OSCs to final commercialization. PMID- 26540367 TI - Gestational Weight Gain - United States, 2012 and 2013. PMID- 26540368 TI - Patellar resurfacing in total knee arthroplasty: functional outcome differs with different outcome scores: A randomized, double-blind study of 129 knees with 3 years of follow-up. AB - BACKGROUND AND PURPOSE: Recent research on outcomes after total knee arthroplasty (TKA) has raised the question of the ability of traditional outcome measures to distinguish between treatments. We compared functional outcomes in patients undergoing TKA with and without patellar resurfacing, using the knee injury and osteoarthritis outcome score (KOOS) as the primary outcome and 3 traditional outcome measures as secondary outcomes. PATIENTS AND METHODS: 129 knees in 115 patients (mean age 70 (42-82) years; 67 female) were evaluated in this single center, randomized, double-blind study. Data were recorded preoperatively, at 1 year, and at 3 years, and were assessed using repeated-measures mixed models. RESULTS: The mean subscores for the KOOS after surgery were statistically significantly in favor of patellar resurfacing: sport/recreation, knee-related quality of life, pain, and symptoms. No statistically significant differences between the groups were observed with the Knee Society clinical rating system, with the Oxford knee score, and with visual analog scale (VAS) for patient satisfaction. INTERPRETATION: In the present study, the KOOS--but no other outcome measure used--indicated that patellar resurfacing may be beneficial in TKA. PMID- 26540369 TI - Remote Health Monitoring for Older Adults and Those with Heart Failure: Adherence and System Usability. AB - BACKGROUND: Remote health monitoring technology has been suggested as part of an early intervention and prevention care model. Older adults with a chronic health condition have been shown to benefit from remote monitoring but often have challenges with complex technology. The current study reports on the usability of and adherence with an integrated, real-time monitoring system over an extended period of time by older adults with and without a chronic health condition. MATERIALS AND METHODS: Older adults 55 years of age and over with and without heart failure participated in a study in which a telehealth system was used for 6 months each. The system consisted of a wireless wristwatch-based monitoring device that continuously collected temperature and motion data. Other health information was collected daily using a weight scale, blood pressure cuff, and tablet that participants used for health surveys. Data were automatically analyzed and summarized by the system and presented to study nurses. RESULTS: Forty-one older adults participated. Seventy-one percent of surveys, 75% of blood pressure readings, and 81% of daily weight measurements were taken. Participants wore the watch monitor 77% of the overall 24/7 time requested. The weight scale had the highest usability rating in both groups. The groups did not otherwise differ on device usage. CONCLUSIONS: The findings indicate that a health monitoring system designed for older adults can and will be used for an extended period of time and may help older adults with chronic conditions reside longer in their own homes in partnership with the healthcare system. PMID- 26540370 TI - Addressing the Retrolingual Space in Obstructive Sleep Apnea: Outcomes Stratified by Friedman Stage in Patients Undergoing Transoral Robotic Surgery. AB - BACKGROUND/AIMS: To stratify outcomes in patients with moderate to severe obstructive sleep apnea-hypopnea syndrome (OSAHS) undergoing transoral robotic surgery (TORS) +/- multilevel procedures according to Friedman stage. METHODS: A total of 118 patients with moderate to severe OSAHS between 2010 and 2013 were stratified preoperatively by Friedman stage. All patients had TORS-assisted lingual tonsillectomy, either stand-alone or in combination with palatal surgery. Apnea-hypopnea index (AHI) was measured preoperatively and 3 months postoperatively. Success was defined as a decrease in AHI by 50% and AHI <20. RESULTS: The average pre- and postoperative AHI was 43.0 and 22.6, respectively, and the overall success rate was 63%. When stratifying by Friedman stage, success was seen in 75% of stage I, 70% of stage II, 66% of stage III, and 10% of stage IV patients. When stratifying by preoperative BMI, success was seen in 75% of stage II and 72% of stage III patients with BMI <30, compared to 58% of stage II and 56% of stage III patients with BMI >30. CONCLUSIONS: TORS-assisted lingual tonsillectomy +/- multilevel procedures can be successful in treating patients with moderate to severe OSAHS with Friedman stage I-III anatomy. Success rates are even greater if patients are stratified according to preoperative BMI, as those with BMI <30 are more likely to achieve success even with Friedman stage II III anatomy. PMID- 26540371 TI - Complete mitochondrial genome of Australian spiny lobster, Panulirus cygnus (George, 1962) (Crustacea: Decapoda: Palinuridae) from coast of Australia. AB - We characterized the total mitochondrial genome of Australian spiny lobster, Panulirus cygnus (George, 1962), which is found along the western coast of Australia. Total mitochondrial genome length of P. cygnus was 15 724 bp, in which 13 proteins, 2 ribosomal RNAs, 22 transfer RNAs, and a putative control region were encoded. Nine and four protein-coding genes are encoded on the H-strand and on the L-strand, respectively. According to the phylogenetic analysis, P. cygnus was most closely related to Panulirus japonicus among the compared six species belonging to Palinuridae. Although overall gene organization was the same, the putative control region (between SrRNA gene and tRNAIlel) is least similar to one another among mitochondrial genomes from the compared six species belonging to Palinuridae. PMID- 26540372 TI - Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification. AB - OBJECTIVE: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. MATERIAL AND METHODS: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. RESULTS: Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. CONCLUSION: Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery. PMID- 26540373 TI - The complete mitochondrial genome of the Xenocatantops brachycerus (Orthoptera: Catantopidae). AB - Xenocatantops brachycerus (Orthoptera: Catantopidae), which is widely distributed through China and Southeast Asia, is harmful for the crops. The complete mitochondrial genome of X. brachycerus is 15 605 bp in length and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 A + T-rich region. The gene order of the mitogenome is identical with most orthopteran insects. Most protein-coding genes start with typical ATN codon except for cox1, which initiates with ACC codon instead. While all PCGs use complete stop codons (TAA and TAG). In addition, 13 related species and 2 outgroup taxa were used to construct the phylogenetic tree to further validate the mitogenome of X. brachycerus and research the phylogenetic relationships of Catantopidae. PMID- 26540375 TI - Association between air pollution and hemoptysis. PMID- 26540374 TI - Intravoxel incoherent motion MRI for predicting early response to induction chemotherapy and chemoradiotherapy in patients with nasopharyngeal carcinoma. AB - BACKGROUND: To investigate the value of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DW-MRI) in predicting the early response to induction chemotherapy (IC) and chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC). METHODS: Fifty NPC patients who received IC and CRT underwent an IVIM DW-MRI on a 1.5-Tesla MRI scanner. The pretreatment and posttreatment (20 days after IC initiation) IVIM-based parameters (ADC, D, D*, and f), and their percentage changes (?%), were compared between the effective (complete response or partial response) and ineffective (stable disease) groups based on RECIST 1.1, and between the residual and nonresidual groups. RESULTS: None of the perfusion-related parameter' values showed significant differences between the effective and ineffective groups (p values for pref, postf, ?%f, preD*, postD*, and ?%D* were 0.364, 0.129, 0.792, 0.804, 0.167, and 0.428, respectively), or between the residual and nonresidual groups (P values for pref, postf, ?%f, preD*, postD*, and ?%D* were 0.328, 0.776, 0.546, 0.558, 0.214, and 0.414, respectively). The ineffective group exhibited higher preADC, higher preD and lower ?%D values than the effective group (all P < 0.001). The nonresidual group had lower preD, lower preADC and higher ?%D values (all P < 0.05) than the residual group. ?%D had the highest area under curve (0.859) in predicting the response to IC, whereas preD had the highest area under curve (0.841) in predicting tumor residue after CRT. CONCLUSION: Diffusion-related IVIM-based parameters might be more helpful than perfusion-related parameters in predicting the early effects of IC and CRT for NPC. PMID- 26540376 TI - Patient isolation precautions: Are they worth it? PMID- 26540377 TI - Unimolecular Submersible Nanomachines. Synthesis, Actuation, and Monitoring. AB - Unimolecular submersible nanomachines (USNs) bearing light-driven motors and fluorophores are synthesized. NMR experiments demonstrate that the rotation of the motor is not quenched by the fluorophore and that the motor behaves in the same manner as the corresponding motor without attached fluorophores. No photo or thermal decomposition is observed. Through careful design of control molecules with no motor and with a slow motor, we found using single molecule fluorescence correlation spectroscopy that only the molecules with fast rotating speed (MHz range) show an enhancement in diffusion by 26% when the motor is fully activated by UV light. This suggests that the USN molecules give ~9 nm steps upon each motor actuation. A non-unidirectional rotating motor also results in a smaller, 10%, increase in diffusion. This study gives new insight into the light actuation of motorized molecules in solution. PMID- 26540378 TI - Sharing data to save lives. PMID- 26540379 TI - Driving CARs: as 'living drugs', T cell therapies face dose standardization woes. PMID- 26540380 TI - Delivering the goods: scientists seek a way to make CRISPR-Cas gene editing more targeted. PMID- 26540381 TI - Model network: Canadian program aims to generate models for rare disease. PMID- 26540383 TI - A pathway to HIV-1 neutralization breadth. PMID- 26540384 TI - A TGF-beta pathway associated with cancer cachexia. PMID- 26540385 TI - Personalizing pancreatic cancer organoids with hPSCs. PMID- 26540386 TI - Targeting Toll-like receptors to treat chronic pain. PMID- 26540387 TI - The emerging role of lncRNAs in cancer. AB - It is increasingly evident that many of the genomic mutations in cancer reside inside regions that do not encode proteins. However, these regions are often transcribed into long noncoding RNAs (lncRNAs). The recent application of next generation sequencing to a growing number of cancer transcriptomes has indeed revealed thousands of lncRNAs whose aberrant expression is associated with different cancer types. Among the few that have been functionally characterized, several have been linked to malignant transformation. Notably, these lncRNAs have key roles in gene regulation and thus affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. This review aims to summarize current knowledge of lncRNAs from the cancer perspective. It discusses the strategies that led to the identification of cancer related lncRNAs and the methodologies and challenges involving the study of these molecules, as well as the imminent applications of these findings to the clinic. PMID- 26540388 TI - Genipin diffusion and reaction into a gelatin matrix for tissue engineering applications. AB - Genipin is a natural low-toxic cross-linker for molecules with primary amino groups, and its use with collagen and gelatin has shown a great potential in tissue engineering applications. The fabrication of scaffolds with a well organized micro and macro topology using additive manufacturing systems requires an accurate control of working parameters, such as reaction rate, gelling time, and diffusion constant. A polymeric system of 5% w/v gelatin in PBS with 2 mg/mL collagen solutions in a 1:1 weight ratio was used as template to perform measurements varying genipin concentration in a range of 0.1-1.5% w/w with respect to gelatin. In the first part of this work, the reaction rate of the polymeric system was estimated using a new colorimetric analysis of the reaction. Then its workability time, closely related to the gelling time, was evaluated thanks to rheological analysis: finally, the quantification of static and dynamic diffusion constants of genipin across nonreacting and reacting membranes, made respectively by agarose and gelatin, was performed. It was shown that the colorimetric analysis is a good indicator of the reaction progress. The gelling time depends on the genipin concentration, but a workability window of 40 min guaranteed up to 0.5% w/w genipin. The dynamic diffusion constant of genipin in the proposed polymeric system is in the order of magnitude of 10-7 . The obtained results indicated the possibility to use the genipin, gelatin, and collagen, in the proposed concentrations, to build well-defined hydrogel scaffolds with both extrusion-based and 3D ink-jet system. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 473-480, 2017. PMID- 26540389 TI - Lower Extremity Edema, Anxiety, and Cyanosis During Chemoradiation Therapy for Glioblastoma. PMID- 26540390 TI - Flexible Organic Tribotronic Transistor Memory for a Visible and Wearable Touch Monitoring System. AB - A new type of flexible organic tribotronic transistor memory is proposed, which can be written and erased by externally applied touch actions as an active memory. By further coupling with an organic light-emitting diode (OLED), a visible and wearable touch monitoring system is achieved, in which touch triggering can be memorized and shown as the emission from the OLED. PMID- 26540391 TI - Detection and Antimicrobial Resistance of Vibrio Isolates in Aquaculture Environments: Implications for Public Health. AB - The aim of this study was to evaluate the presence of Vibrio isolates recovered from four different fish pond facilities in Benin City, Nigeria, determine their antibiogram profiles, and evaluate the public health implications of these findings. Fish pond water samples were collected from four sampling sites between March and September 2014. A total of 56 samples were collected and screened for the isolation of Vibrio species using standard culture-based methods. Polymerase chain reaction (PCR) was used to confirm the identities of the Vibrio species using the genus-specific and species-specific primers. Vibrio species were detected at all the study sites at a concentration on the order of 10(3) and 10(6) CFU/100 ml. A total of 550 presumptive Vibrio isolates were subjected to PCR confirmation. Of these isolates, 334 isolates tested positive, giving an overall Vibrio prevalence rate of 60.7%. The speciation of the 334 Vibrio isolates from fish ponds yielded 32.63% Vibrio fluvialis, 20.65% Vibrio parahaemolyticus, 18.26% Vibrio vulnificus, and 28.44% other Vibrio species. In all, 167 confirmed Vibrio isolates were selected from a pool of 334 confirmed Vibrio isolates for antibiogram profiling. The susceptibility profiles of 20 antimicrobial agents on the isolates revealed a high level of resistance for AMP(R), ERY(R), NAL(R), SUL(R), TMP(R), SXT(R), TET(R), OTC(R), and CHL(R). The percentage of multiple drug resistance Vibrio isolates was 67.6%. The multiple antibiotic resistance index mean value of 0.365 for the Vibrio isolates found in this study indicated that the Vibrio isolates were exposed to high-risk sources of contamination when antibiotics were frequently used. The resistant Vibrio strains could be transmitted through the food chain to humans and therefore constitutes a risk to public health. PMID- 26540392 TI - Seropositivity among Korean Young Adults Approximately 2 Years after a Single Dose Vaccination against Hepatitis A Virus. AB - We previously observed 80.7% seropositivity and a significant interaction between gender and hepatitis A virus (HAV) vaccine type (Havrix vs. Epaxal) on the seropositivity approximately 11 months after single-dose HAV vaccinations in Korean young adults. Our objective was to evaluate seropositivity approximately 2 years after a single-dose HAV vaccination and the influence of demographic characteristics on seropositivity, including the interaction between gender and vaccine type. Seronegative medical school students were randomly vaccinated with Havrix or Epaxal. Based on a total serum anti-HAV antibody titer cutoff of 20 IU/mL, 338 participants (76.0%) of the 445 vaccinees were seropositive 20-25 months after a single-dose HAV vaccination. The seropositive rates were similar after vaccination with Havrix (77.0%) and Epaxal (74.9%). Univariate analysis indicated that female (p = 0.052) and less obese (p < 0.001) participants had a higher seropositive rate, whereas other characteristics such as age, alcohol use, smoking history, vaccine type, and follow-up duration were not associated with seropositivity. Multivariate analysis indicated that women (p = 0.026) and participants with moderate alcohol use (p < 0.001) showed significantly higher seropositive rates than men and participants with no or low alcohol use, respectively. The seropositive rates after vaccination with Havrix and Epaxal were 70.9% and 67.5% in men and 87.7% and 91.3% in women, respectively (p for interaction = 0.304). Compared with the seropositive rate approximately 11 months after vaccination, the seropositive rate decreased substantially only in men in the Havrix group (11.0% points), and consequently, the interaction between gender and vaccine type disappeared while seropositivity remained high (87.7% and 91.3% in Havrix and Epaxal groups, respectively) among women approximately 2 years after vaccination. Further studies are needed to assess whether the seropositive rate would be maintained in all groups more than 2 years after a single-dose HAV vaccination. PMID- 26540394 TI - The Effects of Saline Water Drip Irrigation on Tomato Yield, Quality, and Blossom End Rot Incidence --- A 3a Case Study in the South of China. AB - Saline water resources are abundant in the coastal areas of south China. Most of these resources still have not been effectively utilized. A 3-year study on the effects of saline water irrigation on tomato yield, quality and blossom-end rot (BER) was conducted at different lower limits of soil matric potential (-10 kPa, 20 kPa, -30 kPa, -40 kPa and -50 kPa). Saline water differing in electrical conductivity (EC) (3 dS/m, 4 dS/m, 4.5 dS/m, 5 dS/m and 5.5 dS/m) was supplied to the plant after the seedling establishment. In all three years, irrigation water with 5.5 dS/m salinity reduced the maximum leaf area index (LAIm) and chlorophyll content the most significantly when compared with other salinity treatments. However, compared with the control treatment (CK), a slight increase in LAIm and chlorophyll content was observed with 3~4 dS/m salinity. Saline water improved tomato quality, including fruit density, soluble solid, total acid, vitamin C and the sugar-acid ratio. There was a positive relationship between the overall tomato quality and salinity of irrigation water, as analyzed by principal component analysis (PCA). The tomato yield decreased with increased salinity. The 5.5 dS/m treatment reduced the tomato yield (Yt) by 22.4~31.1%, 12.6~28.0% and 11.7~27.3%, respectively in 2012, 2013 and 2014, compared with CK. Moreover, a significant (P<=0.01) coupling effect of salinity and soil matric potential on Yt was detected. Saline water caused Yt to increase more markedly when the lower limit of soil matric potential was controlled at a relatively lower level. The critical salinity level that produced significant increases in the BERi was 3 dS/m~4 dS/m. Following the increase in BERi under saline water irrigation, marketable tomato yield (Ym) decreased by 8.9%~33.8% in 2012, 5.1%~30.4% in 2013 and 10.1%~32.3% in 2014 compared with CK. In terms of maintaining the Yt and Ym, the salinity of irrigation water should be controlled under 4 dS/m, and the lower limit of soil matric potential should be greater than -20 kPa. PMID- 26540393 TI - A Putative Non-Canonical Ras-Like GTPase from P. falciparum: Chemical Properties and Characterization of the Protein. AB - During its development the malaria parasite P. falciparum has to adapt to various different environmental contexts. Key cellular mechanisms involving G-protein coupled signal transduction chains are assumed to act at these interfaces. Heterotrimeric G-proteins are absent in Plasmodium. We here describe the first cloning and expression of a putative, non-canonical Ras-like G protein (acronym PfG) from Plasmodium. PfG reveals an open reading frame of 2736 bp encoding a protein of 912 amino acids with a theoretical pI of 8.68 and a molecular weight of 108.57 kDa. Transcript levels and expression are significantly increased in the erythrocytic phase in particular during schizont and gametocyte formation. Most notably, PfG has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases in a variety of Bacillus species and Mycobacteria. By contrast, plasmodial PfG is divergent from any human alpha subunit. PfG was expressed in E. coli as a histidine-tagged fusion protein and was stable only for 3.5 hours. Purification was only possible under native conditions by Nickel-chelate chromatography and subsequent separation by Blue Native PAGE. Binding of a fluorescent GTP analogue BODIPY(r) FL guanosine 5'O (thiotriphosphate) was determined by fluorescence emission. Mastoparan stimulated GTP binding in the presence of Mg2+. GTPase activity was determined colorimetrically. Activity expressed as absolute fluorescence was 50% higher for the human paralogue than the activity of the parasitic enzyme. The PfG protein is expressed in the erythrocytic stages and binds GTP after immunoprecipitation. Immunofluorescence using specific antiserum suggests that PfG localizes to the parasite cytosol. The current data suggest that the putitative, Ras-like G protein might be involved in a non-canonical signaling pathway in Plasmodium. Research on the function of PfG with respect to pathogenesis and antimalarial chemotherapy is currently under way. PMID- 26540395 TI - Studying the Motivated Agent Through Time: Personal Goal Development During the Adult Life Span. AB - This research examined the rank-order and mean-level consistency of personal goals at two periods in the adult life span. Personal goal continuity was considered among a group of young adults (N = 145) who reported their goals three times over a 3-year period and among a group of midlife adults (N = 163) who specified their goals annually over a 4-year period. Goals were coded for a series of motive-based (viz., achievement, affiliation, intimacy, power) and domain-based (viz., finance, generativity, health, travel) categories. In both samples, we noted a moderate degree of rank-order consistency across assessment periods. In addition, the majority of goal categories exhibited a high degree of mean-level consistency. The results of this research suggest that (a) the content of goals exhibits a modest degree of rank-order consistency and a substantial degree of mean-level consistency over time, and (b) considering personality continuity and development as manifest via goals represents a viable strategy for personality psychologists. PMID- 26540396 TI - The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial. AB - OBJECTIVE: Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission. DESIGN: Follow-up study of a randomized clinical trial. SETTING: Five Dutch heart centers. PATIENTS: Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. INTERVENTIONS: A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. MEASUREMENTS AND MAIN RESULTS: Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. CONCLUSIONS: Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present. PMID- 26540397 TI - Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study. AB - OBJECTIVE: To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist >= 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3). DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. PATIENTS: Sixty eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. INTERVENTIONS: Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist >= 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale >= 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale <= 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. CONCLUSIONS: Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. PMID- 26540398 TI - Economic Evaluation of Telemedicine for Patients in ICUs. AB - OBJECTIVE: Despite telemedicine's potential to improve patients' health outcomes and reduce costs in the ICU, hospitals have been slow to introduce telemedicine in the ICU due to high up-front costs and mixed evidence on effectiveness. This study's first aim was to conduct a cost-effectiveness analysis to estimate the incremental cost-effectiveness ratio of telemedicine in the ICU, compared with ICU without telemedicine, from the healthcare system perspective. The second aim was to examine potential cost saving of telemedicine in the ICU through probabilistic analyses and break-even analyses. DESIGN: Simulation analyses performed by standard decision models. SETTING: Hypothetical ICU defined by the U.S. literature. PATIENTS: Hypothetical adult patients in ICU defined by the U.S. literature. INTERVENTIONS: The intervention was the introduction of telemedicine in the ICU, which was assumed to affect per-patient per-hospital-stay ICU cost and hospital mortality. Telemedicine in the ICU operation costs included the telemedicine equipment-installation (start-up) costs with 5-year depreciation, maintenance costs, and clinician staffing costs. Telemedicine in the ICU effectiveness was measured by cumulative quality-adjusted life years for 5 years after ICU discharge. MEASUREMENTS AND MAIN RESULTS: The base case cost effectiveness analysis estimated telemedicine in the ICU to extend 0.011 quality adjusted life years with an incremental cost of $516 per patient compared with ICU without telemedicine, resulting in an incremental cost-effectiveness ratio of $45,320 per additional quality-adjusted life year (= $516/0.011). The probabilistic cost-effectiveness analysis estimated an incremental cost effectiveness ratio of $50,265 with a wide 95% CI from a negative value (suggesting cost savings) to $375,870. These probabilistic analyses projected that cost saving is achieved 37% of 1,000 iterations. Cost saving is also feasible if the per-patient per-hospital-stay operational cost and physician cost were less than $422 and less than $155, respectively, based on break-even analyses. CONCLUSIONS: Our analyses suggest that telemedicine in the ICU is cost effective in most cases and cost saving in some cases. The thresholds of cost and effectiveness, estimated by break-even analyses, help hospitals determine the impact of telemedicine in the ICU and potential cost saving. PMID- 26540399 TI - Comparison Between Neurally Adjusted Ventilatory Assist and Pressure Support Ventilation Levels in Terms of Respiratory Effort. AB - OBJECTIVES: To understand the potential equivalence between neurally adjusted ventilatory assist and pressure support ventilation levels in terms of respiratory muscle unloading. To compare the respiratory pattern, variability, synchronization, and neuromuscular coupling within comparable ranges of assistance. DESIGN: Prospective single-center physiologic study. SETTING: A 13 bed university medical ICU. PATIENTS: Eleven patients recovering from respiratory failure. INTERVENTIONS: The following levels of assistance were consecutively applied in a random order: neurally adjusted ventilatory assist levels: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, and 7 cm H2O/MUvolt; pressure support levels: 7, 10, 15, 20, and 25 cm H2O. MEASUREMENTS AND MAIN RESULTS: Flow, airway pressure, esophageal pressures, and peak electrical activity of the diaphragm were continuously recorded. Breathing effort was calculated. To express the percentage of assist assumed by the ventilator, the total pressure including muscular and ventilator pressure was calculated. The median percentage of assist ranged from 33% (24-47%) to 82% (72-90%) between pressure support 7 and 25 cm H2O. Similar levels of unloading were observed for neurally adjusted ventilatory assist levels from 0.5 cm H2O/MUvolt (46% [40-51%]) to 2.5 cm H2O/MUvolt (80% [74-84%]). Tidal variability was higher during neurally adjusted ventilatory assist and ineffective efforts appeared only in pressure support. In neurally adjusted ventilatory assist, double triggering occurred sometimes when electrical activity of the diaphragm signal depicted a biphasic aspect, and an abnormal oscillatory pattern was frequently observed from 4 cm H2O/MUvolt. For both modes, the relationship between peak electrical activity of the diaphragm and muscle pressure depicted a curvilinear profile. CONCLUSIONS: In patients recovering from acute respiratory failure, levels of neurally adjusted ventilatory assist between 0.5 and 2.5 cm H2O/MUvolt are comparable to pressure support levels ranging from 7 to 25 cm H2O in terms of respiratory muscle unloading. Neurally adjusted ventilatory assist provides better patient-ventilator interactions but can be sometimes excessively sensitive to electrical activity of the diaphragm in terms of triggering. PMID- 26540400 TI - A Dysregulated Balance of Proinflammatory and Anti-Inflammatory Host Cytokine Response Early During Therapy Predicts Persistence and Mortality in Staphylococcus aureus Bacteremia. AB - OBJECTIVES: The contribution of individual immune response to Staphylococcus aureus bacteremia on outcome has not been well studied. The objective was to relate the host cytokine response to outcome of Staphylococcus aureus bacteremia. DESIGN: Prospective observational study. SETTING: Three U.S. university affiliated medical centers. PATIENTS: Adult patients infected with Staphylococcus aureus bacteremia hospitalized between July 2012 and August 2014. INTERVENTIONS: Blood specimens were obtained at Staphylococcus aureus bacteremia onset and 72 hours after therapy initiation. Levels of tissue necrosis factor, interleukin-6, interleukin-8, interleukin-17A, and interleukin-10 were measured by enzyme-linked immunosorbent assay at each time point and compared between those with persistent bacteremia (>= 4 d) and resolving bacteremia. Primary outcome was persistent bacteremia after 4 days of effective therapy. Secondary outcomes were 30-day mortality and 30-day recurrence. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included (mean age, 59 yr); of them, 33% had methicillin-resistant Staphylococcus aureus bacteremia. Forty-seven percent of the methicillin resistant Staphylococcus aureus strains were staphylococcal cassette chromosome mec IV. Persistent bacteremia occurred in 24% of patients (47/196); they were more likely to die than resolving bacteremia group (28% vs 5%; p < 0.001). Compared with resolving bacteremia group, persistent bacteremia patients had higher initial median levels of tissue necrosis factor (44.73 vs 21.68 pg/mL; p < 0.001), interleukin-8 (124.76 vs 47.48 pg/mL; p = 0.028), and interleukin-10 (104.31 vs 29.72 pg/mL; p < 0.001). Despite 72 hours of treatment, levels remained higher for the persistent bacteremia group than for the resolving bacteremia group (tissue necrosis factor: 26.95 vs 18.38 pg/mL, p = 0.02; interleukin-8: 70.75 vs 27.86 pg/mL, p = 0.002; interleukin-6: 67.50 vs 21.81 pg/mL, p = 0.005; and interleukin-10: 30.98 vs 12.60 pg/mL, p < 0.001). Interleukin-17A levels were similar between groups at both time points. After controlling for confounding variables by multivariate analysis, interleukin 10/tissue necrosis factor ratio at 72 hours most significantly predicted persistence (odds ratio, 2.98; 95% CI, 1.39-6.39; p = 0.005) and mortality (odds ratio, 9.87; 95% CI, 2.64-36.91; p < 0.001) at values more than 1.00 and more than 2.56, respectively. CONCLUSIONS: Sustained elevation of interleukin 10/tissue necrosis factor ratio at 72 hours suggests a dysregulated immune response and may be used to guide management to improve outcomes. PMID- 26540401 TI - Interleukin-17A Is Associated With Alveolar Inflammation and Poor Outcomes in Acute Respiratory Distress Syndrome. AB - OBJECTIVE: Interleukin-17A is a proinflammatory cytokine known to play a role in host defense and pathologic inflammation in murine models of lung injury. The relationship between interleukin-17A and inflammation in human lung injury is unknown. Our primary objective was to determine whether interleukin-17A levels are associated with alveolar measures of inflammation and injury in patients with acute respiratory distress syndrome. Our secondary objective was to test whether interleukin-17A levels are associated with acute respiratory distress syndrome related outcomes. DESIGN: Observational study. SETTING: Six North American medical centers. PATIENTS: We studied two groups of patients with acute respiratory distress syndrome: 1) patients previously enrolled in a placebo controlled clinical trial of omega-3 fatty acids performed at five North American medical centers (n = 86, acute respiratory distress syndrome 1), and 2) patients with systemic inflammatory response syndrome admitted to an ICU who developed acute respiratory distress syndrome (n = 140, acute respiratory distress syndrome 2). In acute respiratory distress syndrome 1, we used paired serum and bronchoalveolar lavage fluid samples obtained within 48 hours of acute respiratory distress syndrome onset, whereas in acute respiratory distress syndrome 2, we used plasma obtained within the first 24 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured circulating interleukin-17A in acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2. We also measured interleukin-17A, neutrophil counts, and total protein in bronchoalveolar lavage fluid from acute respiratory distress syndrome 1. We found that bronchoalveolar lavage interleukin-17A was strongly associated with higher bronchoalveolar lavage percent neutrophils (p < 0.001) and bronchoalveolar lavage total protein (p < 0.01) in acute respiratory distress syndrome1. In both acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2, elevated interleukin-17A was associated with higher Sequential Organ Failure Assessment scores (p < 0.05). CONCLUSIONS: Elevated circulating and alveolar levels of interleukin-17A are associated with increased percentage of alveolar neutrophils, alveolar permeability, and organ dysfunction in acute respiratory distress syndrome. PMID- 26540403 TI - Nod-like receptor pyrin containing 3 (NLRP3) in the post-mortem frontal cortex from patients with bipolar disorder: A potential mediator between mitochondria and immune-activation. AB - Mitochondrial complex I dysfunction, oxidative stress and immune-activation are consistently reported in bipolar disorder (BD). Mitochondrial production of reactive oxygen species was recently linked to activation of an inflammatory redox sensor, the nod-like receptor family pyrin domain-containing 3 (NLRP3). Upon its activation, NLRP3 recruits apoptosis-associated speck-like protein (ASC) and caspase-1 to form the NLRP3-inflammasome, activating IL-1beta. This study aimed to examine if immune-activation may be a downstream target of complex I dysfunction through the NLRP3-inflammasome in BD. Post-mortem frontal cortex from patients with BD (N = 9), schizophrenia (N = 10), and non-psychiatric controls (N = 9) were donated from the Harvard Brain Tissue Resource Center. Levels of NLRP3, ASC and caspase-1 were measured by western blotting, ELISA and Luminex. While we found no effects of age, sex or post-mortem delay, lower levels of complex I (F2,25 = 3.46, p < 0.05) and NDUFS7, a subunit of complex I (F2,25 = 4.13, p < 0.05), were found in patients with BD. Mitochondrial NLRP3 (F2,25 = 3.86, p < 0.05) and ASC (F2,25 = 4.61, p < 0.05) levels were higher in patients with BD. However, levels of caspase 1 (F2,25 = 4.13, p < 0.05 for both), IL-1beta (F2,25 = 7.05, p < 0.01), IL-6 (F2,25 = 5.48, p < 0.05), TNFalpha (F2,25 = 7.14, p < 0.01) and IL-10 (F2,25 = 5.02, p < 0.05) were increased in both BD and schizophrenia. These findings suggest that immune-activation in the frontal cortex may occur both in patients with BD and schizophrenia, while complex I dysfunction and NLRP3 inflammasome activation may be more specific to BD. PMID- 26540402 TI - Evaluation Following Staggered Implementation of the "Rethinking Critical Care" ICU Care Bundle in a Multicenter Community Setting. AB - OBJECTIVES: To evaluate process metrics and outcomes after implementation of the "Rethinking Critical Care" ICU care bundle in a community setting. DESIGN: Retrospective interrupted time-series analysis. SETTING: Three hospitals in the Kaiser Permanente Northern California integrated healthcare delivery system. PATIENTS: ICU patients admitted between January 1, 2009, and August 30, 2013. INTERVENTIONS: Implementation of the Rethinking Critical Care ICU care bundle which is designed to reduce potentially preventable complications by focusing on the management of delirium, sedation, mechanical ventilation, mobility, ambulation, and coordinated care. Rethinking Critical Care implementation occurred in a staggered fashion between October 2011 and November 2012. MEASUREMENTS AND MAIN RESULTS: We measured implementation metrics based on electronic medical record data and evaluated the impact of implementation on mortality with multivariable regression models for 24,886 first ICU episodes in 19,872 patients. After implementation, some process metrics (e.g., ventilation start and stop times) were achieved at high rates, whereas others (e.g., ambulation distance), available late in the study period, showed steep increases in compliance. Unadjusted mortality decreased from 12.3% to 10.9% (p < 0.01) before and after implementation, respectively. The adjusted odds ratio for hospital mortality after implementation was 0.85 (95% CI, 0.73-0.99) and for 30 day mortality was 0.88 (95% CI, 0.80-0.97) compared with before implementation. However, the mortality rate trends were not significantly different before and after Rethinking Critical Care implementation. The mean duration of mechanical ventilation and hospital stay also did not demonstrate incrementally greater declines after implementation. CONCLUSIONS: Rethinking Critical Care implementation was associated with changes in practice and a 12-15% reduction in the odds of short-term mortality. However, these findings may represent an evaluation of changes in practices and outcomes still in the midimplementation phase and cannot be directly attributed to the elements of bundle implementation. PMID- 26540404 TI - Conditional risk for posttraumatic stress disorder in an epidemiological study of a Brazilian urban population. AB - INTRODUCTION: Conditional risk for PTSD is the risk of developing PTSD after exposure to traumatic events. This epidemiological study of the general urban population from the two largest cities in Brazil reports exposure to traumatic events; conditional risk for PTSD; and proportion/estimated number of PTSD cases secondary to each type of traumatic event. METHOD: Cross-sectional study of general population (15-75 y.o.) from Rio de Janeiro and Sao Paulo. PTSD was assessed through Composite International Diagnostic Interview 2.1. RESULTS: Our main findings, from 3744 participants, were: 1) high prevalence of traumatic events (86%), urban violence being the most common; 2) conditional risk for PTSD was 11.1%; 3) women (15.9%) have overall conditional risk 3 times higher than men (5.1%); 4) war-related trauma (67.8%), childhood sexual abuse (49.1%) and adult sexual violence (44.1%) had the highest conditional risks; 5) 35% of PTSD cases (estimated 435,970 individuals) were secondary to sudden/unexpected death of a close person, and 40% secondary to interpersonal violence. CONCLUSIONS: Brazilian urban population is highly exposed to urban violence, and overall conditional risk for PTSD was 11.1%. Violence prevention and enhancement of resilience should be part of public policies, and mental health sequelae of trauma should be better recognized and treated. PMID- 26540405 TI - Decreased mRNA expression for the two subunits of system xc(-), SLC3A2 and SLC7A11, in WBC in patients with schizophrenia: Evidence in support of the hypo glutamatergic hypothesis of schizophrenia. AB - BACKGROUND: The cystine/glutamate antiporter system xc(-), playing a critical role in the regulation of glutamate release, might be implicated in the pathogenesis of schizophrenia. This study examined whether peripheral expressions of the system xc(-) subunits are characteristic of schizophrenia. METHODS: Expression of system xc(-) genes including SLC3A2 and SLC7A11 in peripheral WBCs of patients with schizophrenia and healthy individuals were measured using quantitative PCR. Both psychotropic-free and medicated patients with schizophrenia were recruited. RESULTS: A total of 96 schizophrenia patients (48 medicated and 48 drug-free) and 96 healthy individuals were enrolled. The mRNA expression levels using the 2(-DeltaDeltaC)T Method of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients were markedly lower than that of healthy individuals (0.22 and 0.48, respectively, the mRNA expression level of normal controls was normalized to 1). There was no significant difference between medicated and drug-free patients in the mRNA expressions of both SLC3A2 and SLC7A11. The Receiver Operating Characteristics (ROC) analysis of SLC3A2 mRNA levels using DeltaDeltaCT values for drug-free schizophrenia patients vs. healthy controls determined an optimal cutoff value, 0.801, with high sensitivity (1.000) and modest specificity (0.694) (area under curve of ROC = 0.794). CONCLUSION: This is the first study indicating that the peripheral mRNA expression levels of SLC7A11 and SLC3A2 may be lower in patients with schizophrenia than healthy individuals. The finding supports the hypo-glutamatergic neurotransmission hypothesis in schizophrenia. Whether mRNA expression of system xc(-) subunits genes, particularly SLC3A2, could serve as a potential biomarker of schizophrenia needs further studies. PMID- 26540406 TI - X chromosome reactivation in reprogramming and in development. AB - Dramatic epigenetic changes take place during mammalian differentiation from the naive pluripotent state including the silencing of one of the two X chromosomes in female cells through X chromosome inactivation. Conversely, reprogramming of somatic cells to naive pluripotency is coupled to X chromosome reactivation (XCR). Recent studies in the mouse system have shed light on the mechanisms of XCR by uncovering the timing and steps of XCR during reprogramming to induced pluripotent stem cells (iPSCs), allowing the generation of testable hypotheses during embryogenesis. In contrast, analyses of the X chromosome in human iPSCs have revealed important differences between mouse and human reprogramming processes that can partially be explained by the establishment of distinct pluripotent states and impact disease modeling and the application of human pluripotent stem cells. Here, we review recent literature on XCR as a readout and determinant of reprogramming to pluripotency. PMID- 26540408 TI - Socioeconomic Disparities and Prevalence of Autism Spectrum Disorders and Intellectual Disability. AB - BACKGROUND AND OBJECTIVES: Study of the impact of socioeconomic status on autism spectrum disorders (ASD) and severe intellectual disabilities (ID) has yielded conflicting results. Recent European studies suggested that, unlike reports from the United States, low socioeconomic status is associated with an increased risk of ASD. For intellectual disabilities, the links with socioeconomic status vary according to the severity. We wished to clarify the links between socioeconomic status and the prevalence of ASD (with or without ID) and isolated severe ID. METHODS: 500 children with ASD and 245 children with severe ID (IQ <50) aged 8 years, born 1995 to 2004, were recruited from a French population-based registry. Inclusions were based on clinical diagnoses reported in medical records according to the International Classification of Diseases, 10th Revision. Socioeconomic status was measured by indicators available at block census level which characterize the population of the child's area of residence. Measures of deprivation, employment, occupation, education, immigration and family structure were used. Prevalences were compared between groups of census units defined by the tertiles of socioeconomic level in the general population. RESULTS: Prevalence of ASD with associated ID was higher in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. No association was found when using occupational class. Regarding ASD without associated ID, a higher prevalence was found in areas with the highest percentage of immigrants. No association was found for other socioeconomic indicators. The prevalence of isolated severe ID was likely to be higher in the most disadvantaged groups defined by all indicators. CONCLUSION: The prevalence of ASD with associated ID and of severe isolated ID is more likely to be higher in areas with the highest level of deprivation. PMID- 26540407 TI - The p53 tumor suppressor protein protects against chemotherapeutic stress and apoptosis in human medulloblastoma cells. AB - Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. Currently, survivors carry a significant burden of late treatment effects. The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. Herein, we report that the experimental drug VMY-1-103 acts through induction of a partial DNA damage-like response as well induction of non-survival autophagy. Surprisingly, the genetic or chemical silencing of p53 significantly enhanced the cytotoxic effects of both VMY and the DNA damaging drug, doxorubicin. The inhibition of p53 in the presence of VMY revealed increased late stage apoptosis, increased DNA fragmentation and increased expression of genes involved in apoptosis, including CAPN12 and TRPM8, p63, p73, BIK, EndoG, CIDEB, P27Kip1 and P21cip1. These data provide the groundwork for additional studies on VMY as a therapeutic drug and support further investigations into the intriguing possibility that targeting p53 function may be an effective means of enhancing clinical outcomes in MB. PMID- 26540409 TI - Synchronization of Spontaneous Active Motility of Hair Cell Bundles. AB - Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID- 26540411 TI - Siglec-9 modulated IL-4 responses in the macrophage cell line RAW264. AB - Siglecs, an immunoglobulin-like lectin family that recognizes the sialic acid moiety, regulate various aspects of immune responses. In the present study, we investigated the effects of Siglecs on the macrophage cell line RAW264, which was stimulated with interleukin-4 (IL-4). The induction of arginase-1 (Arg1) by IL-4 was stronger in Siglec-9-expressing cells than in mock cells. Mutations in the cytoplasmic tyrosine-based inhibitory motifs in Siglec-9 markedly reduced the expression of Arg1. The phosphorylation of Akt by IL-4 and extracellular signal regulated kinase (ERK) without IL-4 was stronger in Siglec-9-expressing cells, indicating the enhanced activation of the phosphatidylinositol 3 kinase (PI-3K) and mitogen-activated protein kinase kinase (MEK)/ERK pathways, respectively. The enhanced expression of Arg1 was inhibited by MEK inhibitors, but not by PI-3K inhibitor. These results indicate that Siglec-9 affects several different signaling pathways in IL-4-stimulated macrophages, which resulted in enhanced induction of Arg1 in Siglec-9-expressing RAW264 cells. PMID- 26540413 TI - Ligand Based Dual Fluorescence and Phosphorescence Emission from BODIPY Platinum Complexes and Its Application to Ratiometric Singlet Oxygen Detection. AB - Four new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacen-8-yl (BODIPY) platinum(II) complexes of the type cis-/trans-Pt(BODIPY)Br(PR3)2 (R = Et or Ph) were synthesized and characterized by NMR, electronic absorption, and luminescence spectroscopy. Three of the complexes were also studied by single crystal X-ray diffraction. The absorption profiles of the four complexes feature intense HOMO > LUMO pi -> pi* transitions with molar extinction coefficients epsilon of ca. 50 000 M(-1)cm(-1) at around 475 nm and vibrational progressions that are characteristic of BODIPYs. Most remarkably, most complexes exhibit dual emissions through fluorescence at ca. 490 nm and phosphorescence at ca. 650 nm that originate from Pt-perturbed BODIPY-centered (1)pipi* or (3)pipi* states, respectively. Electronic absorption and luminescence spectroscopy data are in good agreement with our TD-DFT calculations. While the emission of the cis complexes is dominated by fluorescence, their trans-isomers emit predominantly through phosphorescence with a phosphorescence quantum yield for trans Pt(BODIPY)Br(PEt3)2 (trans-1) of 31.2%. trans-1 allows for ratiometric one component oxygen sensing in fluid solution up to atmospheric concentration levels and exhibits a remarkably high Stern-Volmer constant for the quenching of the excited triplet state by oxygen of ca. 350 bar(-1) as determined by changes in phosphorescence intensity and lifetime. PMID- 26540412 TI - Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador. AB - OBJECTIVES: To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. METHODS: We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). RESULTS: In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. CONCLUSIONS: Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID- 26540414 TI - Bronchial Thermoplasty: Targeting Structural Cells in Severe Persistent Asthma. PMID- 26540410 TI - Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases. AB - Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resulting in more than one disease or trait. Patterns of pleiotropy may be helpful in understanding the underlying causes of an array of conditions in a population. For example, several fibroproliferative diseases are more prevalent and severe in populations of sub-Saharan ancestry. We propose that this disparity is due to selection for an enhanced Th2 response that confers resistance to helminthic infections, and concurrently increases susceptibility to fibrosis due to the profibrotic action of Th2 cytokines. Many studies on selection of Th2-related genes for host resistance to helminths have been reported, but the pleiotropic impact of this selection on the distribution of fibrotic disorders has not been explicitly investigated. We discuss the disproportionate occurrence of fibroproliferative diseases in individuals of African ancestry and provide evidence that adaptation of the immune system has shaped the genetic structure of these human populations in ways that alter the distribution of multiple fibroproliferative diseases. PMID- 26540415 TI - The Challenge and the Promise of Studying Mitochondrial Dysfunction in Humans with Sepsis. PMID- 26540416 TI - Variation and Cost-effectiveness of Quality Measurement Programs. The Case of Sepsis Bundles. PMID- 26540417 TI - Editors' Introduction to "Ultrasound Reflections". PMID- 26540418 TI - Keeping Hope: My 10-Year Journey with Cancer. PMID- 26540419 TI - ATS Core Curriculum 2015: Part III. Pediatric Pulmonary Medicine. PMID- 26540420 TI - Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units. PMID- 26540421 TI - Implications of Marijuana Decriminalization on the Practice of Pulmonary, Critical Care, and Sleep Medicine. A Report of the American Thoracic Society Marijuana Workgroup. PMID- 26540422 TI - A Cryptic Consolidation. PMID- 26540423 TI - Bronchoscopic Management of a Benign Obstructing Pedunculated Tumor. PMID- 26540424 TI - Shock in a Man with HIV Infection and a Large Mediastinal Mass. PMID- 26540425 TI - Ultrasound Diagnosis of Dyspnea in a Patient with Systemic Lupus Erythematosus. PMID- 26540426 TI - Apnea in New-Onset Heart Failure. PMID- 26540427 TI - Rare Becomes More Common: Recognizing Neuroendocrine Cell Hyperplasia of Infancy in Everyday Pulmonary Consultations. PMID- 26540428 TI - Endobronchial Ultrasound-guided Transbronchial Needle Aspiration while Receiving Aspirin and Clopidogrel: Is It Always Safe? PMID- 26540429 TI - Enhancing Endobronchial Ultrasound Images Using a Water-based Lubricant Technique. PMID- 26540430 TI - Treatment of Malignant Airway Obstruction with Intratumoral Injection of Chemotherapy with Cisplatin. PMID- 26540431 TI - Reply: Treatment of Malignant Airway Obstruction with Intratumoral Injection of Chemotherapy with Cisplatin. PMID- 26540432 TI - Getting the Full Diagnostic Picture in Intensive Care Medicine: A Plea for "Physiological Examination". PMID- 26540433 TI - Reply: Getting the Full Diagnostic Picture in Intensive Care Medicine: A Plea for "Physiological Examination". PMID- 26540435 TI - Role of Bai-Shao towards the antidepressant effect of Chaihu-Shu-Gan-San using metabonomics integrated with chemical fingerprinting. AB - Chaihu-Shu-Gan-San (CSGS) is a classical traditional Chinese medicine formula for the treatment of depression. As one of the single herbs in CSGS, Bai-Shao displayed antidepressant effect. In order to explore the role of Bai-Shao towards the antidepressant effect of CSGS, the metabolic regulation and chemical profiles of CSGS with and without Bai-Shao (QBS) were investigated using metabonomics integrated with chemical fingerprinting. At first, partial least squares regression (PLSR) analysis was applied to characterize the potential biomarkers associated with chronic unpredictable mild stress (CUMS)-induced depression. Among 46 differential metabolites found in the ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) and (1)H NMR-based urinary metabonomics, 20 were significantly correlated with the preferred sucrose consumption observed in behavior experiments and were considered as biomarkers to evaluate the antidepressant effect of CSGS. Based on differential regulation on CUMS-induced metabolic disturbances with CSGS and QBS treatments, we concluded that Bai-Shao made crucial contribution to CSGS in the improvement of the metabolic deviations of six biomarkers (i.e., glutamate, acetoacetic acid, creatinine, xanthurenic acid, kynurenic acid, and N acetylserotonin) disturbed in CUMS-induced depression. While the chemical constituents of Bai-Shao contributed to CSGS were paeoniflorin, albiflorin, isomaltopaeoniflorin, and benzoylpaeoniflorin based on the multivariate analysis of the UPLC-Q-TOF/MS chemical profiles from CSGS and QBS extracts. These findings suggested that Bai-Shao played an indispensable role in the antidepressant effect of CSGS. PMID- 26540436 TI - Serum metabolomics in rats models of ketamine abuse by gas chromatography-mass spectrometry. AB - This study aims to evaluate the effect of ketamine on rats by examining the differences in serum metabolites between ketamine abuse group (Ket-group) and control group (Con-group). Compared to the Con-group, the level of phosphate, propanoic acid, ribitol and d-fructose of the Ket-group increased after continuous intraperitoneal administration of ketamine for 7 days, while the level of alanine, glycine, butanoic acid, valine, l-serine, l-proline, mannonic acid, octadecanoic acid and cholesterol decreased. After 14 days' administration, the level of alanine, butanoic acid, valine, l-leucine, phosphate, l-serine, l threonine, propanetricarboxylic acid, hexadecanoic acid and oleic acid of the ketamine group increased while the level of mannonic acid, octadecanoic acid and cholesterol decreased. After stopping ketamine administration for 2 days, the level of butanoic acid, phosphate, aminomalonic acid, gluconic acid, hexadecanoic acid, oleic acid and arachidonic acid of Ket-group increased, while the level of glycine, l-lysine and cholesterol decreased. This study can provide invaluable information for the metabolites changes due to ketamine abuse. PMID- 26540438 TI - Surfactant Behavior of Sodium Dodecylsulfate in Deep Eutectic Solvent Choline Chloride/Urea. AB - Deep eutectic solvents (DES) resemble ionic liquids but are formed from an ionic mixture instead of being a single ionic compound. Here we present some results that demonstrate that surfactant sodium dodecyl sulfate (SDS) remains surface active and shows self-assembly phenomena in the most commonly studied DES, choline chloride/urea. X-ray reflectivity (XRR) and small angle neutron scattering (SANS) suggest that the behavior is significantly different from that in water. Our SANS data supports our determination of the critical micelle concentration using surface-tension measurements and suggests that the micelles formed in DES do not have the same shape and size as those seen in water. Reflectivity measurements have also demonstrated that the surfactants remain surface-active below this concentration. PMID- 26540437 TI - High performance liquid chromatography tandem mass spectrometry assay for the determination of cobinamide in pig plasma. AB - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been widely utilized for the analysis of compounds in biological matrices due to its selectivity and sensitivity. This study describes the application of an LC-MS/MS based approach toward the analysis of cobinamide in Yorkshire pig plasma. The selectivity, accuracy, precision, recovery, linearity, range, carryover, sensitivity, matrix effect, interference, stability, reproducibility, and ruggedness of the method were investigated in pig plasma. The accuracy and precision of the method was determined to be within 10% over three different days over a range of concentrations (25-10,000ng/mL) that spanned more than two orders of magnitude. The lower limit of quantitation (LLOQ) for dicyanocobinamide was determined to be 25ng/mL in pig plasma. Carryover was acceptable, as the area response of the carryover blanks were <=15% of the area response of the nearest LLOQ standard for the analyte, while it was nonexistent for the internal standard. Specificity was ensured using six different lots of pig plasma. While the matrix effects of dicyanocobinamide in plasma were enhanced, ginsenoside Rb1 experienced signal suppression under the described conditions. The absolute recovery results for both compounds were consistent, precise, and reproducibly lower than expected at ~60% for dicyanocobinamide and ~22% for ginsenoside Rb1, confirming that a matrix standard curve was required for accurate quantitation. Cobinamide was shown to be very stable in matrix at various storage conditions including room temperature, refrigerated, and frozen at time intervals of 20h, 4 days, and 60 days respectively. This method was demonstrated to be sensitive, reproducible, stable, and rugged, and it should be applicable to the analysis of cobinamide in other biological matrices and species. PMID- 26540439 TI - Correction: Lactobacillus acidophilus Alleviates Platelet-Activating Factor Induced Inflammatory Responses in Human Intestinal Epithelial Cells. PMID- 26540440 TI - IMGT/HighV-QUEST Statistical Significance of IMGT Clonotype (AA) Diversity per Gene for Standardized Comparisons of Next Generation Sequencing Immunoprofiles of Immunoglobulins and T Cell Receptors. AB - The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species. PMID- 26540441 TI - Correlation between the signal-to-noise ratio improvement factor (KSNR) and clinical image quality for chest imaging with a computed radiography system. AB - This work assessed the appropriateness of the signal-to-noise ratio improvement factor (KSNR) as a metric for the optimisation of computed radiography (CR) of the chest. The results of a previous study in which four experienced image evaluators graded computer simulated chest images using a visual grading analysis scoring (VGAS) scheme to quantify the benefit of using an anti-scatter grid were used for the clinical image quality measurement (number of simulated patients = 80). The KSNR was used to calculate the improvement in physical image quality measured in a physical chest phantom. KSNR correlation with VGAS was assessed as a function of chest region (lung, spine and diaphragm/retrodiaphragm), and as a function of x-ray tube voltage in a given chest region. The correlation of the latter was determined by the Pearson correlation coefficient. VGAS and KSNR image quality metrics demonstrated no correlation in the lung region but did show correlation in the spine and diaphragm/retrodiaphragmatic regions. However, there was no correlation as a function of tube voltage in any region; a Pearson correlation coefficient (R) of -0.93 (p = 0.015) was found for lung, a coefficient (R) of -0.95 (p = 0.46) was found for spine, and a coefficient (R) of -0.85 (p = 0.015) was found for diaphragm. All demonstrate strong negative correlations indicating conflicting results, i.e. KSNR increases with tube voltage but VGAS decreases. Medical physicists should use the KSNR metric with caution when assessing any potential improvement in clinical chest image quality when introducing an anti-scatter grid for CR imaging, especially in the lung region. This metric may also be a limited descriptor of clinical chest image quality as a function of tube voltage when a grid is used routinely. PMID- 26540442 TI - Influence of Immobilization Time on Functional Outcome in Radial Neck Fractures in Children. AB - Background Radial neck fractures represent 20 to 30% of elbow fractures in children. Incorrect treatment can lead to significant permanent functional impairment. Posttraumatic avascular necrosis may cause a deformity of the radial head and neck. Deformation of the radial head and neck can be more severe after open rather than closed reduction or orthopedic treatment without reduction. The aim of our study was to analyze the influence of immobilization time on functional outcome. Patients and Methods Retrospective, descriptive study of all children who had been treated for a radial neck fracture between 1999 and 2013 at the University Children's Hospital Basel. Patients were allocated to two groups (group 1: patients treated between 1999 and 2008, group 2: patients treated between 2009 and 2013). The fractures were classified according to the classification of Metaizeau. The primary endpoint was the percentage of patients who reached the full range of elbow motion at the end of the treatment period or the last follow-up. Secondary endpoints were immobilization time and number of patients with persistent physical restrictions of the elbow range of motion as well as the type of restrictions and subjective complaints. Results A total of 67 patients treated for radial neck fracture were included in the first group (1999 2008). A total of 47 patients were allocated to the second group (2009-2013). Overall, 59 patients in group 1 and 39 patients in group 2 were treated nonoperatively. Average immobilization time was 22.7 days (range, 6-60 days) in group 1 and 13.2 days (range, 0-27 days) in group 2. Full range of motion was observed in 50 to 72.7% of patients in group 1 and in 71.4 to 92% of patients in group 2, depending on the grade of fracture displacement. Overall, 21 patients (31%) of group 1 showed a persistent functional restriction. In group 2, only six patients (12%) suffered from a persistent functional restriction of the elbow range of motion. Conclusion Aside from the severity of fracture displacement and treatment modality (conservative vs. operative, closed vs. open reduction), the duration of immobilization may also influence the functional outcome. Further prospective studies are required to confirm our results. PMID- 26540443 TI - The Role of Activin Receptor-Like Kinase 1 Signaling in the Pulmonary Vasculature of Experimental Diaphragmatic Hernia. AB - AIM: The high morbidity and mortality in newborn infants diagnosed with congenital diaphragmatic hernia (CDH) is widely recognized to be due to pulmonary hypoplasia and persistent pulmonary hypertension (PH). The underlying structural and molecular pathomechanisms causing PH are not fully understood. Recently, activin receptor-like kinase 1 (ALK-1), an endothelial cell (EC) receptor, has been implicated in the pathogenesis of PH. ALK-1 transmits signals via a Smad pathway stimulating EC proliferation and migration leading to structural lung remodeling consecutively resulting in PH. Increased pulmonary expression of ALK-1 has been reported in patients with severe PH as well as in experimental models of PH. We designed this study to investigate the hypothesis that pulmonary ALK-1 expression is increased in nitrofen-induced CDH. METHODS: Pregnant rats were exposed to nitrofen or vehicle on D9. Fetuses were sacrificed on D21 and divided into nitrofen (n = 16) and control group (n = 16). Quantitative real-time polymerase chain reaction, Western blotting, and confocal-immunofluorescence microscopy were performed to determine pulmonary gene and protein expression as well as vascular localization of expressed ALK-1. RESULTS: Pulmonary gene expression levels of ALK-1 were significantly upregulated in nitrofen-treated lung tissue compared with controls. Western blotting showed increased pulmonary protein expression for ALK-1 in the CDH group when compared with control lung tissue. Confocal microscopy demonstrated markedly increased medial and adventitial thickness of pulmonary arteries in the CDH group and revealed increased ALK-1 protein expression of the pulmonary vasculature of CDH pups compared with controls. CONCLUSION: Upregulated gene and increased protein expression of ALK-1 in the pulmonary vasculature of nitrofen-induced CDH suggest that increased expression of ALK-1 may play a crucial role in the molecular pathogenesis of vascular remodeling induced PH in experimental CDH. PMID- 26540444 TI - Pediatric Bulbar and Posterior Urethral Injuries: Operative Outcomes and Long Term Follow-Up. AB - AIM: The aim of this study was to analyze complications and outcomes of end-to end urethral anastomosis performed for posttraumatic bulbar strictures or posterior urethral injuries in pediatric patients. METHODS: The records of 15 boys, age 18 years and below, admitted to our tertiary trauma center with urethral injuries from 1989 to 2014 were reviewed retrospectively. Out of these 15 boys, 7 were excluded (2 for iatrogenic trauma, 2 for minor straddle injuries who were not operated on, 2 for incomplete records, and 1 lost to follow-up) and 8 analyzed patients were operated for bulbar or posterior urethral injury. The mean follow-up after the operation was 4.5 years (range 0.5-10). To obtain up-to date follow-up information, all the analyzed patients were contacted by a letter and telephone in January 2015 and asked about lower urinary tract or erectile dysfunction (ED) using the International Index of Erectile Function-5 questionnaire. RESULTS: Mean age at the time of injury was 12.3 years (range 5 17). Four patients with pelvic fracture had complete posterior urethra disruption, three patients after straddle injury developed obliterating stricture of the bulbar urethra and one patient had torn his bulbar urethra apart by a sharp hook. Except for the immediate exploration of the open perineal wound, all patients were operated via perineal approach 1 to 6 months after initial suprapubic catheter insertion. Five patients needed a cystotomy to identify the proximal urethral stump by a probe, and two patients had partial pubectomy to gain urethral length. Postoperative complications included stricture in anastomosis in six patients (all reoperated, four more than once including attempts of endoscopic internal urethrotomy). Six days after surgery, one patient developed massive external bleeding around a permanent urinary catheter due to a posttraumatic ruptured arterial aneurysm that was later stopped by urgent angiography and coil insertion. After discharge, three patients had transient stress incontinence. All patients had uroflowmetry maximum flow above 20 mL/s on their last follow-up except for two (12 and 15 mL/s). None have any lower urinary tract dysfunction symptoms in adulthood; one suffers from mild ED and two report moderate ED due to penile shortening. CONCLUSION: Delayed end-to-end anastomosis for pediatric urethral injury is a safe operational option. However, high rate of short-term complications and reoperations should be expected. Penile shortening is one of the most severe long-term complications. PMID- 26540445 TI - Interspecies quantitative structure-activity relationships (QSARs) for eco toxicity screening of chemicals: the role of physicochemical properties. AB - In addition to molecular structure profiles, descriptors based on physicochemical properties are useful for explaining the eco-toxicities of chemicals. In a previous study we reported that a criterion based on the difference between the partition coefficient (log POW) and distribution coefficient (log D) values of chemicals enabled us to identify aromatic amines and phenols for which interspecies relationships with strong correlations could be developed for fish daphnid and algal-daphnid toxicities. The chemicals that met the log D-based criterion were expected to have similar toxicity mechanisms (related to membrane penetration). Here, we investigated the applicability of log D-based criteria to the eco-toxicity of other kinds of chemicals, including aliphatic compounds. At pH 10, use of a log POW - log D > 0 criterion and omission of outliers resulted in the selection of more than 100 chemicals whose acute fish toxicities or algal growth inhibition toxicities were almost equal to their acute daphnid toxicities. The advantage of log D-based criteria is that they allow for simple, rapid screening and prioritizing of chemicals. However, inorganic molecules and chemicals containing certain structural elements cannot be evaluated, because calculated log D values are unavailable. PMID- 26540446 TI - Estimating PM2.5 Concentrations in Xi'an City Using a Generalized Additive Model with Multi-Source Monitoring Data. AB - Particulate matter with an aerodynamic diameter <2.5 MUm (PM2.5) represents a severe environmental problem and is of negative impact on human health. Xi'an City, with a population of 6.5 million, is among the highest concentrations of PM2.5 in China. In 2013, in total, there were 191 days in Xi'an City on which PM2.5 concentrations were greater than 100 MUg/m3. Recently, a few studies have explored the potential causes of high PM2.5 concentration using remote sensing data such as the MODIS aerosol optical thickness (AOT) product. Linear regression is a commonly used method to find statistical relationships among PM2.5 concentrations and other pollutants, including CO, NO2, SO2, and O3, which can be indicative of emission sources. The relationships of these variables, however, are usually complicated and non-linear. Therefore, a generalized additive model (GAM) is used to estimate the statistical relationships between potential variables and PM2.5 concentrations. This model contains linear functions of SO2 and CO, univariate smoothing non-linear functions of NO2, O3, AOT and temperature, and bivariate smoothing non-linear functions of location and wind variables. The model can explain 69.50% of PM2.5 concentrations, with R2 = 0.691, which improves the result of a stepwise linear regression (R2 = 0.582) by 18.73%. The two most significant variables, CO concentration and AOT, represent 20.65% and 19.54% of the deviance, respectively, while the three other gas-phase concentrations, SO2, NO2, and O3 account for 10.88% of the total deviance. These results show that in Xi'an City, the traffic and other industrial emissions are the primary source of PM2.5. Temperature, location, and wind variables also non linearly related with PM2.5. PMID- 26540447 TI - Racial Variations in Velopharyngeal and Craniometric Morphology in Children: An Imaging Study. AB - PURPOSE: The purpose of this study is to examine craniometric and velopharyngeal anatomy among young children (4-8 years of age) with normal anatomy across Black and White racial groups. METHOD: Thirty-two healthy children (16 White and 16 Black) with normal velopharyngeal anatomy participated and successfully completed the magnetic resonance imaging scans. Measurements included 11 craniofacial and 9 velopharyngeal measures. RESULTS: Two-way analysis of covariance was used to determine the effects of race and sex on velopharyngeal measures and all craniometric measures except head circumference. Head circumference was included as a covariate to control for overall cranial size. Sex did not have a significant effect on any of the craniometric measures. Significant racial differences were demonstrated for face height. A significant race effect was also observed for mean velar length, velar thickness, and velopharyngeal ratio. CONCLUSION: The present study provides separate craniofacial and velopharyngeal values for young Black and White children. Data from this study can be used to examine morphological variations with respect to race and sex. PMID- 26540448 TI - Children teach methods they could not discover for themselves. AB - Across three studies (N=100), we explored whether and, if so, under what circumstances children's self-discovered knowledge impacts their transmission of taught information. All participants were taught one of several methods for extracting rewards from a box. Half of the participants were also given an opportunity to discover their own method prior to receiving such instruction. Across studies, we varied the transparency of the taught method relative to the method children could discover on their own. When asked to teach a naive pupil about the box, children who did not explore the box always transmitted what they were taught. Children in the Exploration+Instruction condition were also likely to transmit what they had been taught, but they were especially likely to do so when the taught method was more opaque than the method they had discovered for themselves. Thus, children faithfully transmit what they have been taught, but only when that information is difficult to discover. PMID- 26540449 TI - Protective Effect of Areca catechu Leaf Ethanol Extract Against Ethanol-Induced Gastric Ulcers in ICR Mice. AB - Gastric ulcer is a common digestive disorder that results in considerable suffering. Hence, this digestive pathology has been the focus of a number of recent studies. Although numerous drugs have been developed to treat gastric ulcers, therapeutic approaches for many of the complications associated with these drugs remain to be identified. For this reason, many natural compounds have been explored as alternatives for these drugs. In this study, we have investigated the effectiveness of Areca catechu leaf ethanol extract (ACE) for treating ethanol-induced gastric ulcers in mice. We performed histological as well as immunohistochemical examinations to explore the therapeutic properties of ACE. We also examined the levels of inflammatory signaling molecules to confirm the anti-inflammatory effects of ACE. The histochemical data demonstrate that ACE can protect the mucosal epithelium as well as the vascular supply in the gastric tract. Furthermore, ACE significantly reduced the expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 receptor (IL-6R), inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and nuclear factor-kappa B (NF-kappaB). Taken together, these data suggest that ACE administration may have the potential as an alternative treatment for gastric ulcer because of its cytoprotective and anti-inflammatory effects and ability to promote the rejuvenation and revascularization of the damaged gastric epithelium. PMID- 26540450 TI - Quantitative Shear-Wave US Elastography of the Supraspinatus Muscle: Reliability of the Method and Relation to Tendon Integrity and Muscle Quality. AB - PURPOSE: To evaluate the reliability of ultrasonographic (US) elastography of the supraspinatus (SSP) muscle, define normal shear-wave velocity (SWV) values, and correlate findings with tendon integrity and muscle quality. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written informed consent was obtained from all patients. SSP SWV (in meters per second) was prospectively assessed twice in 22 asymptomatic volunteers (mean age +/- standard deviation, 53.8 years +/- 15.3; 11 women and 11 men) by two independent examiners by using shear-wave elastography. Forty-four patients (mean age, 51.9 years +/- 15.0; 22 women and 22 men) were prospectively included. SWV findings were compared with tendon integrity, tendon retraction (Patte classification), fatty muscle infiltration (Goutallier stages 0-IV), and muscle volume atrophy (tangent sign) on magnetic resonance (MR) images. Descriptive statistics, Spearman correlation, analysis of variance, two-sample t test, and intraclass correlation coefficient (ICC) were used. RESULTS: Test-retest reliability for mean total SWV (MTSWV) was good for examiner 1 (ICC = 0.70; 95% confidence interval [CI]: 0.30, 0.87; P = .003) and excellent for examiner 2 (ICC = 0.80; 95% CI: 0.53, 0.92; P < .001). Interexaminer reliability was excellent (ICC = 0.89; 95% CI: 0.64, 0.96; P < .001). MTSWV in volunteers (3.0 m/sec +/- 0.5) was significantly higher than that in patients (2.5 m/sec +/- 0.5; P = .001). For tendon integrity, no significant difference in MTSWV was found. For tendon retraction, MTSWV varies significantly between patients with different degrees of retraction (P = .047). No significant differences were found for Goutallier subgroups. MTSWV was significantly lower with a positive tangent sign (P = .015; n = 10). CONCLUSION: Shear-wave elastography is reproducible for assessment of the SSP muscle. Mean normal SSP SWV is 3.0 m/sec +/- 0.5. SWV decreases with increasing fat content (Goutallier stage 0-III) and increases in the final stage of fatty infiltration (Goutallier stage IV). PMID- 26540451 TI - Expectant management of veterans with early-stage prostate cancer. AB - BACKGROUND: For certain men with low-risk prostate cancer, aggressive treatment results in marginal survival benefits while exposing them to urinary and sexual side effects. Nevertheless, expectant management has been underused. In the current study, the authors evaluated the association between various factors and expectant management use among veterans diagnosed with prostate cancer. METHODS: The authors identified men diagnosed with prostate cancer in 2008. The outcome of interest was use of expectant management, based on documentation captured through an in-depth chart review. Multivariable regression models were fit to examine associations between use of expectant management and patient demographics, cancer severity, and facility characteristics. The authors assessed variation across 21 tertiary care regions and 52 facilities by generating predicted probabilities for receipt of expectant management. RESULTS: Expectant management was more common among patients aged >=75 years (40% vs 27% for those aged < 55 years; odds ratio, 2.57) and those with low-risk tumors (49% vs 20% for patients with high-risk tumors; odds ratio, 5.35). There was no association noted between patient comorbidity and receipt of expectant management (P = .90). There were also no associations found between facility factors and use of expectant management (all P>.05). Among ideal candidates for expectant management, receipt of expectant management varied considerably across individual facilities (0%-85%; P<.001). CONCLUSIONS: Patient age and tumor risk were found to be more strongly associated with use of expectant management than patient comorbidity. Although use of expectant management appears broadly appropriate, there was variation in expectant management noted between hospitals that was apparently not attributable to facility factors. Research determining the basis of this variation, with a focus on providers, will be critical to help optimize prostate cancer treatment for veterans. PMID- 26540453 TI - Motor impairment among different psychiatric disorders: Can patterns be identified? AB - The aim of this study was to explore motor impairment in male adolescents suffering from psychiatric conditions. Taking into account the heterogeneity of a clinical population, motor profiles of distinctive diagnostic groups were evaluated. Whether or not motor ability discriminates between several diagnostic categories was investigated. The Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) was administered to examine a detailed motor profile. The motor abilities of a clinical population (n=144) were compared to those of typically developing peers (n=87), using independent t-tests. To account for differences in intellectual functioning, a one-way ANCOVA was performed. To investigate the extent to which a specific diagnosis contributes to variation in motor scores a stepwise linear regression approach was applied. Results indicated that the clinical group performed significantly worse in comparison to the control group on all BOT-2 scales, even after controlling for IQ. The constructed models indicated that diagnostic categories accounted for a significant amount of the variance in motor ability scores. The results imply that motor ability of adolescents with a psychiatric disorder is in need of attention, regardless of the diagnosis and support the notion that objective motor assessment should be part of routine clinical practice. PMID- 26540454 TI - Kinematic and ground reaction force accommodation during weighted walking. AB - Weighted walking is a functional activity common in daily life and can influence risks for musculoskeletal loading, injury and falling. Much information exists about weighted walking during military, occupational and recreational tasks, but less is known about strategies used to accommodate to weight carriage typical in daily life. The purposes of the study were to examine the effects of weight carriage on kinematics and peak ground reaction force (GRF) during walking, and explore relationships between these variables. Twenty subjects walked on a treadmill while carrying 0, 44.5 and 89 N weights in front of the body. Peak GRF, sagittal plane joint/segment angular kinematics, stride length and center of mass (COM) vertical displacement were measured. Changes in peak GRF and displacement variables between weight conditions represented accommodation. Effects of weight carriage were tested using analysis of variance. Relationships between peak GRF and kinematic accommodation variables were examined using correlation and regression. Subjects were classified into sub-groups based on peak GRF responses and the correlation analysis was repeated. Weight carriage increased peak GRF by an amount greater than the weight carried, decreased stride length, increased vertical COM displacement, and resulted in a more extended and upright posture, with less hip and trunk displacement during weight acceptance. A GRF increase was associated with decreases in hip extension (|r|=.53, p=.020) and thigh anterior rotation (|r|=.57, p=.009) displacements, and an increase in foot anterior rotation displacement (|r|=.58, p=.008). Sub-group analysis revealed that greater GRF increases were associated with changes at multiple sites, while lesser GRF increases were associated with changes in foot and trunk displacement. Weight carriage affected walking kinematics and revealed different accommodation strategies that could have implications for loading and stability. PMID- 26540452 TI - Spatio-Temporal Gene Expression Profiling during In Vivo Early Ovarian Folliculogenesis: Integrated Transcriptomic Study and Molecular Signature of Early Follicular Growth. AB - BACKGROUND: The successful achievement of early ovarian folliculogenesis is important for fertility and reproductive life span. This complex biological process requires the appropriate expression of numerous genes at each developmental stage, in each follicular compartment. Relatively little is known at present about the molecular mechanisms that drive this process, and most gene expression studies have been performed in rodents and without considering the different follicular compartments. RESULTS: We used RNA-seq technology to explore the sheep transcriptome during early ovarian follicular development in the two main compartments: oocytes and granulosa cells. We documented the differential expression of 3,015 genes during this phase and described the gene expression dynamic specific to these compartments. We showed that important steps occurred during primary/secondary transition in sheep. We also described the in vivo molecular course of a number of pathways. In oocytes, these pathways documented the chronology of the acquisition of meiotic competence, migration and cellular organization, while in granulosa cells they concerned adhesion, the formation of cytoplasmic projections and steroid synthesis. This study proposes the involvement in this process of several members of the integrin and BMP families. The expression of genes such as Kruppel-like factor 9 (KLF9) and BMP binding endothelial regulator (BMPER) was highlighted for the first time during early follicular development, and their proteins were also predicted to be involved in gene regulation. Finally, we selected a data set of 24 biomarkers that enabled the discrimination of early follicular stages and thus offer a molecular signature of early follicular growth. This set of biomarkers includes known genes such as SPO11 meiotic protein covalently bound to DSB (SPO11), bone morphogenetic protein 15 (BMP15) and WEE1 homolog 2 (S. pombe)(WEE2) which play critical roles in follicular development but other biomarkers are also likely to play significant roles in this process. CONCLUSIONS: To our knowledge, this is the first in vivo spatio-temporal exploration of transcriptomes derived from early follicles in sheep. PMID- 26540455 TI - Dynamic Peptide Library for the Discovery of Charge Transfer Hydrogels. AB - Coupling of peptide self-assembly to dynamic sequence exchange provides a useful approach for the discovery of self-assembling materials. In here, we demonstrate the discovery and optimization of aqueous, gel-phase nanostructures based on dynamically exchanging peptide sequences that self-select to maximize charge transfer of n-type semiconducting naphthalenediimide (NDI)-dipeptide bioconjugates with various pi-electron-rich donors (dialkoxy/hydroxy/amino naphthalene or pyrene derivatives). These gel-phase peptide libraries are characterized by spectroscopy (UV-vis and fluorescence), microscopy (TEM), HPLC, and oscillatory rheology and it is found that, of the various peptide sequences explored (tyrosine Y-NDI with tyrosine Y, phenylalanine F, leucine L, valine V, alanine A or glycine G-NH2), the optimum sequence is tyrosine-phenylalanine in each case; however, both its absolute and relative yield amplification is dictated by the properties of the donor component, indicating cooperativity of peptide sequence and donor/acceptor pairs in assembly. The methodology provides an in situ discovery tool for nanostructures that enable dynamic interfacing of supramolecular electronics with aqueous (biological) systems. PMID- 26540456 TI - A novel Co-Li2O@Si core-shell nanowire array composite as a high-performance lithium-ion battery anode material. AB - We report a novel material of Co-Li2O@Si core-shell nanowire array synthesized via the lithiation of pre-synthesized CoO@Si core-shell nanowire arrays during the first cycle. When the potential window versus lithium was controlled between 0.01-1.2 V, the coated Si shell could be electrochemically active, while the Co Li2O nanowire core could function as a stable mechanical support and an efficient electron conducting pathway during the charge-discharge process. The Co-Li2O@Si core-shell nanowire array anodes exhibit good cyclic stability and high power capability compared to planar Si film electrodes. PMID- 26540457 TI - The Ethics of Disclosure and Counseling of Patients With Thyroid Cancer. PMID- 26540459 TI - The DynDom3D Webserver for the Analysis of Domain Movements in Multimeric Proteins. AB - DynDom3D is a program for the analysis of domain movements in multimeric proteins. Its inputs are two structure files that indicate a possible domain movement, but the onus has been on the user to process the files so that there is the necessary one-to-one equivalence between atoms in the two atom lists. This is often a prohibitive task to carry out manually, which has limited the application of DynDom3D. Here we report on a webserver with a preprocessor that automatically creates an equivalence between atoms using sequence alignment methods. The processed structure files are passed to DynDom3D and the results are presented on a webpage that includes molecular graphics for easy visualization. PMID- 26540460 TI - Prevalence and Characteristics of Infant's Unexplained Breast Preference for Nursing One Breast: A Self-Administered Survey. AB - BACKGROUND: Breastfeeding is recommended by international bodies as the only source of infant nutrition during the first 6 months of life. Sometimes infants prefer to nurse on one breast for no obvious reason (hereafter called infant's unexplained breast preference [IUBP]). IUBP might reduce the rate of exclusive breastfeeding. The prevalence of IUBP is unknown because most of the literature on IUBP so far has been anecdotal. This study's objective was to investigate the prevalence and characteristics of IUBP among healthy infants in Al-Ahsa, Saudi Arabia. MATERIALS AND METHODS: We conducted a population-based, cross-sectional study between March and August 2013 in the Al-Ahsa area, Eastern Province, Saudi Arabia. Healthy infants who had been born at full term (>=37 weeks of gestation) and were 2-24 months of age were included. We distributed 600 self-administered surveys to mothers who attended vaccination clinics in nine primary healthcare centers. RESULTS: Of 478 mothers who responded to the survey, 121 (25.3%) reported unilateral breastfeeding. IUBP was the most common reason for unilateral breastfeeding, with a prevalence of 13.6% (65/478). IUBP developed at a median age of 1 month (range, 1 day-9 months) and was familial in 42.9% of cases. It was the only reason for formula feeding during the first 6 months of life in 18.5% of cases. CONCLUSIONS: IUBP is common, develops very early in life, and can be familial and a reason for formula feeding. However, these findings need to be confirmed in other studies of other populations. PMID- 26540461 TI - GENEDIA Multi Influenza Ag Rapid Test for detection and H1, H3, and H5 subtyping of influenza viruses. AB - BACKGROUND: Rapid identification and subtype determination of influenza virus is important in managing infected patients. Rapid influenza diagnostic tests (RIDTs) are widely used in this manner, but most can only detect influenza A and B viruses without subtyping. A new RIDT, GENEDIA Multi Influenza Ag Rapid Test (GENEDIA), was developed for detection of influenza A and B viruses and also subtyping of influenza A to H1, H3, H5 which has not been possible with other RIDTs. OBJECTIVES: Assess the performance of GENEDIA. STUDY DESIGN: Nasopharyngeal swabs were collected from 274 clinically suspected patients (influenza A/H1N1/2009 (n=50), influenza A/H3 (n=50), influenza B (n=73) and influenza-negative (n=101)) and analyzed with the real-time RT-PCR, GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card. Also, 46 fecal specimens (H5N2 (n=3), H5N3 (n=3)) of spot-billed duck were analyzed with RT-PCR and GENEDIA. RESULTS: Compared to real-time RT-PCR, the sensitivities of GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card were 73.0%, 57.0%, 58.0% for influenza A, respectively, and 68.5%, 65.8%, 57.5% for influenza B, respectively. Specifically, the sensitivity of GENEDIA was 70.0% for influenza A/H1N1/2009 and 76.0% for influenza A/H3. From the avian influenza samples, GENEDIA detected all six H5 subtype without any cross-reactions. CONCLUSION: The GENEDIA Multi Influenza Ag Rapid Test was sensitive in detecting influenza viruses compared with other commercial RIDTs and also useful for rapid subtype determination of influenza A. PMID- 26540462 TI - Characterisation of nosocomial and community-acquired influenza in a large university hospital during two consecutive influenza seasons. AB - BACKGROUND: Nosocomial influenza is increasingly recognized as an important public health threat causing considerable morbidity and mortality each year. However, data on nosocomial influenza is usually collected during outbreaks only and clinical information of nosocomial influenza is sparsely available. OBJECTIVES: To systematically analyse the distribution of nosocomial and community-acquired influenza and epidemiological characteristics in a tertiary care unit in two consecutive seasons. STUDY DESIGN: A retrospective observational study was conducted to identify and characterise cases of nosocomial and community-acquired influenza at Freiburg University hospital from 1 January 2013 to 30 April 2014. A validated multiplex RT-PCR to detect influenza virus and other respiratory pathogens was used throughout. Clinical information was retrieved from the hospital-based information system. RESULTS: Overall, 218 patients with laboratory-confirmed influenza were included (179 in the first, 39 patients in the second season). A rate of 20% of nosocomial influenza was observed throughout. A fatal outcome was recorded for 9% of nosocomial cases, which were mainly associated with influenza virus A(H1N1)pdm09. Nosocomial influenza occurred in all age groups, but fatalities were only observed in patients >=18 years. Patients with nosocomial influenza were significantly older, underwent therapy for blood malignancies and immunosuppressive regimens more frequently, and received solid organ transplantation more often compared to community-acquired patients. CONCLUSIONS: Despite the different distribution of virus subtypes and epidemiological properties between both influenza seasons, the rate of nosocomial cases remained similar. Systematic detection and targeted prevention measures seem mandatory to minimize nosocomial influenza. PMID- 26540463 TI - Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells. AB - Novel carbamate (7a-7h) and carbonate (7i, 7j, and 8) dimers of melampomagnolide B have been synthesized by reaction of the melampomagnolide-B-triazole carbamate synthon 6 with various terminal diamino- and dihydroxyalkanes. Dimeric carbamate products 7b, 7c, and 7f exhibited potent growth inhibition (GI50 = 0.16-0.99 MUM) against the majority of cell lines in the NCI panel of 60 human hematological and solid tumor cell lines. Compound 7f and 8 exhibited anticancer activity that was 300-fold and 1 * 10(6)-fold more cytotoxic than DMAPT, respectively, at a concentration of 10 MUM against rat 9L-SF gliosarcoma cells. Compounds 7a-7j and 8 were also screened against M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and exhibited 2- to 10-fold more potent antileukemic activity against M9-ENL1 cells (EC50 = 0.57-2.90 MUM) when compared to parthenolide (EC50 = 6.0) and showed potent antileukemic activity against five primary AML cell lines (EC50 = 0.76-7.3 MUM). PMID- 26540465 TI - The Gender Gap in Second Language Acquisition: Gender Differences in the Acquisition of Dutch among Immigrants from 88 Countries with 49 Mother Tongues. AB - Gender differences were analyzed across countries of origin and continents, and across mother tongues and language families, using a large-scale database, containing information on 27,119 adult learners of Dutch as a second language. Female learners consistently outperformed male learners in speaking and writing proficiency in Dutch as a second language. This gender gap remained remarkably robust and constant when other learner characteristics were taken into account, such as education, age of arrival, length of residence and hours studying Dutch. For reading and listening skills in Dutch, no gender gap was found. In addition, we found a general gender by education effect for all four language skills in Dutch for speaking, writing, reading, and listening. Female language learners turned out to profit more from higher educational training than male learners do in adult second language acquisition. These findings do not seem to match nurture oriented explanatory frameworks based for instance on a human capital approach or gender-specific acculturation processes. Rather, they seem to corroborate a nature-based, gene-environment correlational framework in which language proficiency being a genetically-influenced ability interacting with environmental factors such as motivation, orientation, education, and learner strategies that still mediate between endowment and acquiring language proficiency at an adult stage. PMID- 26540464 TI - Single fluorescence probes along the reactive center loop reveal site-specific changes during the latency transition of PAI-1. AB - The serine protease inhibitor (serpin), plasminogen activator inhibitor-1 (PAI 1), is an important biomarker for cardiovascular disease and many cancers. It is therefore a desirable target for pharmaceutical intervention. However, to date, no PAI-1 inhibitor has successfully reached clinical trial, indicating the necessity to learn more about the mechanics of the serpin. Although its kinetics of inhibition have been extensively studied, less is known about the latency transition of PAI-1, in which the solvent-exposed reactive center loop (RCL) inserts into its central beta-sheet, rendering the inhibitor inactive. This spontaneous transition is concomitant with a large translocation of the RCL, but no change in covalent structure. Here, we conjugated the fluorescent probe, NBD, to single positions along the RCL (P13-P5') to detect changes in solvent exposure that occur during the latency transition. The results support a mousetrap-like RCL-insertion that occurs with a half-life of 1-2 h in accordance with previous reports. Importantly, this study exposes unique transitions during latency that occur with a half-life of ~5 and 25 min at the P5' and P8 RCL positions, respectively. We hypothesize that the process detected at P5' represents s1C detachment, while that at P8 results from a steric barrier to RCL insertion. Together, these findings provide new insights by characterizing multiple steps in the latency transition. PMID- 26540466 TI - New tumor regression grade for rectal cancer after neoadjuvant therapy and radical surgery. AB - In this retrospective study, we defined a new tumor regression grade (NTRG), which we used to evaluate the prognosis of patients with locally advanced rectal cancer who received neoadjuvant therapy and then underwent radical surgery between June 2004 and October 2011. Calculated as the TRG plus a lymph node score, the NTRG was determined for 347 patients: NTRG 0, 46 patients (13.3%); NTRG 1, 63 (18.2%); NTRG 2, 183 (52.7%); NTRG 3, 30 (8.6%); NTRG 4, 25 (7.2%). Among this group, 45 (97.8%) NTRG 0, 56 (88.9%) NTRG 1, 148 (80.9%) NTRG 2, 24 (66.7%) NTRG 3, and 10 (40.0%) NTRG 4 patients experienced 5-year disease-free survival. We also found that NTRG is significantly associated with 5-year local recurrence, distant metastasis and disease-free survival (P = 0.004, 0.007 and 0.039, respectively). The NTRG may thus be an independent prognostic factor for oncologic outcomes in rectal cancer patients after neoadjuvant therapy and radical surgery, but this conclusion must be validated in randomized trials. PMID- 26540467 TI - Long non-coding RNA expression profiles of hepatitis C virus-related dysplasia and hepatocellular carcinoma. AB - Recently, long non-coding RNAs (lncRNAs) were found to be implicated in cancer progression. However, the contributions of lncRNAs to Hepatitis C virus-related hepatocellular carcinoma (HCC) remain largely unknown. Here, we characterized lncRNA expression in 73 tissue samples from several different developmental stages of HCV-related hepatocarcinogenesis by repurposing microarray data sets. We found that the expression of 7 lncRNAs in preneoplastic lesions and HCC was significantly different. Among these significantly differently expressed lncRNAs, the lncRNA LINC01419 transcripts were expressed at higher levels in early stage HCC compared to dysplasia and as compared with early stage HCC, lncRNA AK021443 level increase in advanced stage HCC while lncRNA AF070632 level decrease in advanced stage HCC. Using quantitative real-time reverse-transcription PCR, we validated that LINC01419 was significantly overexpressed in HBV-related and HCV related HCC when compared with matched non-tumor liver tissues. Moreover, functional predictions suggested that LINC01419 and AK021443 regulate cell cycle genes, whereas AF070632 is associated with cofactor binding, oxidation-reduction and carboxylic acid catabolic process. These findings provide the first large scale survey of lncRNAs associated with the development of hepatocarcinogenesis and may offer new diagnostic biomarkers and therapeutic targets for HCV-related HCC. PMID- 26540468 TI - Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network. AB - High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR 149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4-2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development. PMID- 26540469 TI - Parasomnias are more frequent in shift workers than in day workers. AB - The aim of this study was to investigate whether different shift work schedules were associated with nonrapid eye movement (NREM)- and/or REM-related parasomnias. A total of 2198 nurses with different work schedules participated in a longitudinal cohort study. The parasomnia questions were included in the fourth wave of the data collection, with a response rate of 74.1%. Logistic regression analyses with the different parasomnias as dependent variables were conducted. Nurses working two shift (day and evening) and nurses working three shift (day, evening and night) rotational schedules had increased risk of confusional arousal, a NREM-related parasomnia, compared to nurses working daytime only (odds ratios = 2.10 and 1.71, respectively). Similarly, nurses working two and three shift rotational schedules had increased risk of nightmares, a REM-related parasomnia (odds ratios = 1.64 and 1.57, respectively). The other parasomnias were not significantly associated with work schedule. Working night shifts only was not associated with any of the parasomnias. In conclusion, confusional arousal and nightmares were more commonly reported by nurses working rotational shift work schedules compared to nurses working daytime only. This is likely related to the circadian rhythm misalignment and sleep deprivation caused by such shift schedules. PMID- 26540472 TI - Changes of Accommodative Power in Vitrectomized Eyes with Crystalline Lenses. AB - PURPOSE: To evaluate changes of accommodative power in phakic eyes after uneventful pars plana vitrectomy (PPV) in patients aged younger than 45 years without presbyopia. METHODS: We investigated patients aged younger than 45 years who underwent PPV without crystalline lens extraction because of vitreoretinal disorders. Twelve weeks after vitrectomy, the near point of accommodation, high frequency component of accommodative microfluctuation, axial length, and anterior chamber depth of vitrectomized and contralateral nonvitrectomized eyes were examined. RESULTS: Ten eyes of 10 patients were included. The average patient age was 39.8 (+/-4.3) years. None experienced cataract progression in the vitrectomized eye up to 12 weeks after surgery. Near point of accommodation was significantly lower in the vitrectomized eye than in the opposite eye at 12 weeks after vitrectomy (5.23 [+/-1.39] diopters vs. 5.91 [+/-1.83] diopters, p < 0.001). The high-frequency components in the vitrectomized eyes were significantly greater than those in the contralateral eyes (p = 0.01). However, anterior chamber depth and axial length were similar in value to the preoperative observations. CONCLUSIONS: Uneventful PPV in relatively young patients without presbyopia reduced accommodative power during the early postoperative period with no cataract progression. PMID- 26540471 TI - Individual Letter Contrast Thresholds: Effect of Object Frequency and Noise. AB - PURPOSE: To compare differences in contrast threshold among individual Sloan letters presented in additive white luminance noise and in the absence of noise. METHODS: Contrast threshold for letter identification was measured for three visually normal subjects (aged 22, 25, and 34 years) using letters from the Sloan set (C, D, H, K, N, O, R, S, V, and Z). The letter size was equivalent to 1.5 logMAR (logarithm of the minimum angle of resolution), and the letters were either unfiltered or band-pass filtered to limit the object frequency content (cycles per letter) to a one-octave wide band centered at 1.25, 2.5, 5, and 10 cycles per letter. Letters were presented for an unlimited duration against a uniform adapting field or in the presence of additive white luminance noise. Contrast threshold for each letter was determined using a 10-alternative forced choice interleaved staircase procedure. RESULTS: For standard unfiltered Sloan letters presented against a uniform field, contrast threshold for individual letters differed by as much as a factor of 1.5, consistent with a previous report. When measured in luminance noise, the individual letters differed by as much as a factor of 1.8. Band-pass filtering the letters to include only low object frequencies increased the differences in contrast threshold among the individual letters (about a factor of 3) compared with unfiltered letters and letters filtered into high object frequency bands. CONCLUSIONS: The addition of white luminance noise had relatively small effects on interletter contrast threshold differences, whereas band-pass filtering had large effects on interletter threshold differences, greatly increasing variation among the letters that contained only low object frequencies. Letters that contain only high object frequencies may be useful in the design of letter charts because the interletter threshold differences are relatively small for these optotypes and the object frequency information mediating identification is known. PMID- 26540473 TI - Morning Glory Syndrome with Carotid and Middle Cerebral Artery Vasculopathy. AB - PURPOSE: To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis. CASE REPORT: A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression. CONCLUSIONS: This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact. PMID- 26540470 TI - Fatherhood, marriage and HIV risk among young men in rural Uganda. AB - Compared to a large body of work on how gender may affect young women's vulnerability to HIV, we know little about how masculine ideals and practices relating to marriage and fertility desires shape young men's HIV risk. Using life history interview data with 30 HIV-positive and HIV-negative young men aged 15-24 years, this analysis offers an in-depth perspective on young men's transition through adolescence, the desire for fatherhood and experience of sexual partnerships in rural Uganda. Young men consistently reported the desire for fatherhood as a cornerstone of masculinity and transition to adulthood. Ideally young men wanted children within socially sanctioned unions. Yet, most young men were unable to realise their marital intentions. Gendered expectations to be economic providers combined with structural constraints, such as limited access to educational and income-generating opportunities, led some young men to engage in a variety of HIV-risk behaviours. Multiple partnerships and limited condom use were at times an attempt by some young men to attain some part of their aspirations related to fatherhood and marriage. Our findings suggest that young men possess relationship and parenthood aspirations that - in an environment of economic scarcity - may influence HIV-related risk. PMID- 26540474 TI - Foster Kennedy Syndrome: An Atypical Presentation. AB - PURPOSE: To describe an unusual presentation of Foster Kennedy syndrome (FKS; unilateral optic nerve atrophy with optic nerve edema in the other eye) with optic nerve atrophy and retinal vein occlusion. It is an example of how common clinical features can hide a rare condition or presentation of a disease. Foster Kennedy syndrome is uncommon. Therefore, a space-occupying lesion should be suspected when there is optic atrophy associated with acute pathology of the other eye. CASE REPORT: A 56-year-old man presented with hemiretinal retinal vein occlusion in his right eye. He had previous optic nerve atrophy in his left eye attributed to nonarteritic anterior ischemic optic neuropathy. He lacked cardiovascular or prothrombotic risk factors. Consideration was given whether the presence of contralateral optic atrophy was associated with the retinal vein occlusion. A computed tomographic scan revealed a suprasellar mass. The tumor was excised and identified as meningioma. CONCLUSIONS: Although typical FKS would present with optic nerve atrophy and contralateral optic nerve edema secondary to an intracranial mass, in this case, edema was replaced by a hemiretinal vein occlusion. In optic atrophy that does not show characteristic visual field alterations, typical symptoms, or the classic evolution of a given disease, diagnostic imaging may reveal the etiology. As FKS is uncommon, when there is optic atrophy associated with acute pathology of the other eye, a space-occupying lesion should be suspected. PMID- 26540475 TI - Effect of Ultraviolet Exposure on Impact Resistance of Ophthalmic Lenses. AB - PURPOSE: To investigate the effect of ultraviolet radiation (UVR) on the impact resistance of organic ophthalmic lens materials. METHODS: Plano power CR39, Phoenix, Trilogy, and polycarbonate lenses with various scratch-resistant (SR) and/or antireflection (AR) coatings were obtained in batches of 40 units. All lenses had a nominal thickness of 2 mm. Half of each batch was conditioned following the European Standard EN 168 protocol for the test of resistance to UVR (exposed group). The remaining lenses comprised an unexposed group for that combination of lens substrate and coating treatment. Each group was subjected to ballistic impact with 6-mm steel balls following the ZEST protocol to determine its mean breakage velocity. The difference in mean breakage velocity between exposed and unexposed groups of each combination of lens substrate and coating was assessed for statistical significance. RESULTS: Exposed uncoated CR39 showed a reduction in fracture velocity of 10.3 m/s whereas CR39 with ultra hard coat had a reduction of 3.5 m/s and CR39 with AR and SR coating had a reduction of 4.1 m/s. Scratch-resistant coated Phoenix had a reduction of 4.8 m/s whereas AR coated Phoenix had a reduction of 3.7 m/s. The corresponding reductions for Trilogy were 3.9 and 17.8 m/s. All differences were significant at the p level of less than 0.05. Although we were unable to break unexposed SR-coated polycarbonate lenses with our test apparatus, exposed SR-coated polycarbonate had a mean breakage velocity of 142 m/s. CONCLUSIONS: Our data suggest that extended UVR exposure causes a significant reduction in the impact resistance of the ophthalmic lens substrates commonly used for occupational eye protectors. Protective lenses that have been exposed to high levels of UVR for extended periods should be replaced regularly to maintain optimal impact protection, even if they do not show visible damage owing to wear and tear. PMID- 26540476 TI - In Vivo Confocal Microscopy Use in Endotheliitis. AB - PURPOSE: The use of in vivo confocal microscopy has been valuable in detecting and managing corneal pathology. This case study documents endotheliitis using in vivo confocal microscopy where apparent resolution of endothelial edema on clinical examination resulted in the discovery of subclinical findings with confocal scanning. The purpose of this case study was to discuss a rare corneal pathology and the clinical value of confocal scanning. CASE REPORT: A 30-year-old Asian Indian woman presented with unilateral endotheliitis and trabeculitis of presumed varicella zoster virus etiology. She was treated successfully with oral antiviral and topical corticosteroid therapy. Subclinical endotheliitis was detected using in vivo confocal microscopy, prompting the continuation of prophylactic, low-dose, topical corticosteroid therapy and topical hyperosmotics. CONCLUSIONS: Further research is warranted to better understand the role of confocal microscopy in endotheliitis therapeutic management, endothelial cell count and morphology, and keratic precipitate characterization. To date, prophylactic oral antivirals and/or topical corticosteroids may play a role in immune suppression of the herpes virus, although prospective, randomized, controlled clinical trials have not focused specifically on endotheliitis cases. PMID- 26540477 TI - Distortion Correction of Visante Optical Coherence Tomography Cornea Images. AB - PURPOSE: Quantitative biometry measurements from uncorrected anterior segment optical coherence tomography (AS-OCT) images are inaccurate because of spatial and optical distortions. Prior reported distortion correction equations for the Visante AS-OCT were not reproducible. The goal was to calculate the distortions and provide equations to correct corneal parameters for the Visante AS-OCT to get a central corneal radius of curvature from young and older subjects. METHODS: Five contact lenses (CLs) of known front and back radii of curvature and central thickness were imaged using the Visante AS-OCT (Carl Zeiss, Dublin, CA). Contact lens surface coordinates from Visante images were identified and fitted with a circle using custom Matlab image analysis software. Spatial and optical distortions of the Visante image of the CL radii of curvature and thickness were calculated and corrected. Visante images were also captured from 24 younger (aged 21 to 36 years) and 30 older (aged 36 to 48 years) human subjects. Corneal radii of curvature and thickness measurements from these subjects were corrected, and intrasession and intersession repeatabilities of the corneal parameters were calculated. RESULTS: Root mean square error of radius and power of the CL surfaces after distortion correction were 0.02 mm and 0.18D for the front and 0.011 mm and 0.11D for the back, respectively. Intraclass correlation coefficient for intrasession and intersession repeatability for all the corneal parameters from the human subjects was greater than 0.88 in both age groups. CONCLUSIONS: A distortion correction algorithm was developed for the Visante AS-OCT and applied to extract human corneal radius of curvature measurements. PMID- 26540478 TI - Evaluation of the SVOne: A Handheld, Smartphone-Based Autorefractor. AB - PURPOSE: The SVOne is a portable Hartmann-Shack wavefront aberrometer that can be attached to a smartphone to determine the refractive error of the eye objectively. The aim of the present study was to compare the findings of the SVOne with retinoscopy, subjective refraction, and two commercially available autorefractors (Topcon KR-1W and Righton Retinomax-3). METHODS: Refractive error was assessed both with and without cycloplegia in 50 visually normal, young adults using the five techniques described above. Further, to assess repeatability of the instruments, the entire procedure was repeated in a subgroup of 10 subjects. All data were analyzed in terms of power vectors (M, J0, and J45). RESULTS: No significant difference was observed between the mean values of M (spherical equivalent) for the different techniques. However, a significantly higher mean value of precyclopegic J0 was recorded for the SVOne, which also had the highest limits of agreement for both the J0 and J45 astigmatic components. Retinoscopy and subjective refraction showed the best repeatability (in terms of M values) for precycloplegic and postcycloplegic measurements, respectively. High and significant linear correlations were observed between the subjective findings and the other four techniques. CONCLUSIONS: The results indicate that the SVOne handheld aberrometer provides measurements of refractive error in normal, young individuals that are not significantly different from other subjective and objective procedures. This instrument is valuable for vision screenings, as well as examinations taking place outside the clinical office. It may also serve as an adjunct in the standard optometric examination. PMID- 26540479 TI - Patient and Physician Convenience and the Choice of Intravitreal Anti-Vascular Endothelial Growth Factor Medications. PMID- 26540480 TI - Agronomic, metabolomic and lipidomic characterisation of Sicilian Origanum vulgare (L.) ecotypes. AB - Although Origanum vulgare (L.) has been deeply analysed at phytochemical level, poor knowledge is available regarding non-volatile compounds such as lipids. The aim of this work was to characterise five wild Sicilian Origanum ecotypes from an agronomic, metabolomic and lipidomic perspective. Serradifalco presented higher dry weight and inflorescences/plant than the others while Favara had a significantly higher number of branches per plant and more extensive flowered stratum. Metabolomic analysis, performed with LC-MS-TOF, allowed a preliminary characterisation of the non-volatile metabolome of the five oregano ecotypes Origanum vulgare ssp. hirtum. Twenty-five metabolites were identified belonging to organic acids, amino acids, lysophosphatidylcholines, carnithines, nucleic bases and lysophosphatidylethanolamines. Lipidomic analysis identified 115 polar plant membrane glycerolipid species. Thirteen of them were differentially present in the two chosen ecotypes. The role of these metabolites in plant physiology from a qualitative and pharmacological point of view was discussed. PMID- 26540481 TI - The complete chloroplast genome sequence of wild cucumber (Cucumis sativus var. Hardwickii). AB - The complete chloroplast genome sequence of wild cucumber (Cucumis sativus var. hardwickii) was generated by de novo assembly with low-coverage whole-genome sequence data. The 155 277 bp genome containing a pair of inverted repeats (IRs) of 25 198 bp separated by a large single-copy region of 86 618 bp and a small single-copy region of 18 263 bp. The chloroplast genome contains 130 known genes, including 89 protein-coding genes, eight rRNA genes (four kinds), and 37 tRNA genes (30 kinds). Eighteen genes are duplicated in the inverted repeat regions, 16 genes contain one intron, two genes, and one ycf contain two introns. Phylogenomic analysis showed that C. sativus var. Hardwickii is closely related to C. sativus and C. hystrix. PMID- 26540482 TI - Lanthanum Hexaboride As Novel Interlayer for Improving the Thermal Stability of P3HT:PCBM Organic Solar Cells. AB - For efficient organic photovoltaic (OPV) solar cells, a low work function electrode is necessary to enhance the built-in voltage of the active layer, thereby improving the overall efficiency. Calcium is often used for this purpose in the laboratory; however, its development on a larger scale is impaired by its high reactivity with oxygen and water and the resulting low stability of solar cells under operation. The influence of a novel interlayer, lanthanum hexaboride (LaB6), on the electronic properties of OPV is studied in this work. Similarly to calcium, when LaB6 is used as an interlayer, it enhances the built-in voltage in the device, leading to a higher fill factor (FF) and optimal open circuit voltage (V(oc)). As a result, optimized LaB6-based devices present significantly improved power conversion efficiencies. More importantly, while calcium/aluminum (Ca/Al) and aluminum (Al) cathodes lose their capacity to enhance the internal electrical field during thermal aging, the LaB6/aluminum (LaB6/Al) electrode remains stable. This remarkable effect results in a highly stable V(oc) and flat-band potential during aging. PMID- 26540483 TI - Vital Signs: Multistate Foodborne Outbreaks - United States, 2010-2014. AB - INTRODUCTION: Millions of U.S. residents become ill from foodborne pathogens each year. Most foodborne outbreaks occur among small groups of persons in a localized area. However, because many foods are distributed widely and rapidly, and because detection methods have improved, outbreaks that occur in multiple states and that even span the entire country are being recognized with increasing frequency. METHODS: This report analyzes data from CDC's Foodborne Disease Outbreak Surveillance System to describe multistate foodborne outbreaks that occurred in the United States during 2010-2014. RESULTS: During this 5-year period, 120 multistate foodborne disease outbreaks (with identified pathogen and food or common setting) were reported to CDC. These multistate outbreaks accounted for 3% (120 of 4,163) of all reported foodborne outbreaks, but were responsible for 11% (7,929 of 71,747) of illnesses, 34% (1,460 of 4,247) of hospitalizations, and 56% (66 of 118) of deaths associated with foodborne outbreaks. Salmonella (63 outbreaks), Shiga toxin-producing E. coli (34), and Listeria monocytogenes (12) were the leading pathogens. Fruits (17), vegetable row crops (15), beef (13), sprouts (10), and seeded vegetables (nine) were the most commonly implicated foods. Traceback investigations to identify the food origin were conducted for 87 outbreaks, of which 55 led to a product recall. Imported foods were linked to 18 multistate outbreaks. CONCLUSIONS: Multistate foodborne disease outbreaks account for a disproportionate number of outbreak-associated illnesses, hospitalizations, and deaths relative to their occurrence. Working together, food industries and public health departments and agencies can develop and implement more effective ways to identify and to trace contaminated foods linked to multistate outbreaks. Lessons learned during outbreak investigations can help improve food safety practices and regulations, and might prevent future outbreaks. PMID- 26540484 TI - Value of remote ischaemic preconditioning in rat dorsal skin flaps and clamping time. AB - OBJECTIVE: According to previous reports, remote ischaemic preconditioning (RIPC) is a "delay" procedure that is highly likely to be useful for preventing skin flap necrosis. Differences in the extent of necrosis in rat dorsal skin flaps when different clamping times were used in RIPC were compared among the four groups described below. METHODS: Group A was a control group in which no prior ischaemic area was created, and both back legs were devascularised for 15 min in Group B, 30 min in Group C, and 60 min in Group D. The experiments were performed on 10 rats in each group, and the surviving area was measured. One-way analysis of variance (ANOVA) and Tukey's multiple comparison test were used for analysis, with p < 0.05 regarded as significant. RESULTS: The surviving area of the skin flap was 15.4 +/- 1.8 cm(2) in Group A, 15.4 +/- 2.0 cm(2) in Group B, 17.9 +/- 2.0 cm(2) in Group C, and 19.2 +/- 3.4 cm(2) in Group D, with significant differences between Groups A and D and between Groups B and D. CONCLUSIONS: RIPC consisting of 60 min of ischaemic preconditioning may be clinically useful as a method of preventing skin flap necrosis. PMID- 26540485 TI - Development and Efficacy Testing of a Social Network-Based Competitive Application for Weight Loss. AB - INTRODUCTION: Although a lot of people continuously try to lose weight, the obesity rate has remained high: 36.9% of males and 38.0% of females worldwide in 2013. This suggests the need for a new intervention. MATERIALS AND METHODS: In this study, we designed a smartphone application, With U, to aid weight loss by using an offline social network of friends and an online social network, Facebook. To determine the effects of With U, this study was designed as a one group pretest-posttest design. Overweight, obese, and severely obese adults 20-40 years old, along with their friends, participated in this study. A total of 10 pairs attempted to lose weight for 4 weeks. We used a questionnaire to measure general characteristics, motivation, and intent to continue to use With U, and the Inbody720 (Biospace, Seoul, Republic of Korea) body composition analyzer was used to measure physical characteristics. In addition, we briefly interviewed the participants about their experience. RESULTS: We observed statistically significant effects in terms of motivation to lose weight and the amount of weight loss. Changes in physical characteristics beyond weight loss also showed positive trends. Also, we discovered some interesting facts during the interviews. The weight loss effect was greater when the team members met more and the relationship between the challengers was more direct and intimate. CONCLUSIONS: The application With U, designed and developed to allow friends to challenge each other to lose weight, affected both motivation to lose weight and the amount of weight loss. In the future, effects of smartphone applications for health management with social networks need to be studied further. PMID- 26540486 TI - Four complete mitochondrial genomes of the genera Candidia, Opsariichthys, and Zacco (Cypriniformes: Cyprinidae). AB - Members of Candidia, Nipponcrysis, Parazacco, Opsariichthys, and Zacco are a group of East Asian freshwater fishes, and these five genera form a monophyletic group within the subfamily Oxygastrinae (Cypriniformes: Cyprinidae). In this study, we first determined complete mitogenomes of Candidia pingtungensis, Opsariichthys acutipinnis, O. chengtui, and Zacco acanthogenys. The four mitogenomes with the length of 16 611-16 615 bp displayed the same patterns in gene arrangements and the use of start and stop codons for protein-coding genes. Our phylogeny divided Candidia, Nipponcrysis, Parazacco, Opsariichthys, and Zacco into two major groups that the former three genera consisted of a group and the latter two genera formed another group. The phylogeny also revealed that C. pingtungensis was nested within Nipponcrysis. Our findings indicate that the taxonomy status of Candidia and Nipponcrysis is still needed to be confirmed. PMID- 26540487 TI - A Comparison of the Penetration and Permeation of Caffeine into and through Human Epidermis after Application in Various Vesicle Formulations. AB - BACKGROUND/AIMS: A range of vesicles is now widely used to carry various solutes into and through the epidermis. These usually have the active solute encapsulated within and may be modified to confer flexibility and skin penetration enhancement. Here, we compared the ability of five different vesicle systems to deliver a model hydrophilic drug, caffeine, into and through excised human skin. METHODS: In addition to lipids, the vesicle excipients included eucalyptol or oleic acid as penetration enhancers, and decyl polyglucoside as a non-ionic surfactant. Vesicle particle sizes ranged between 135 and 158 nm, and caffeine encapsulation efficiencies were between 46 and 66%. Caffeine penetration and permeation were measured using high-performance liquid chromatography. RESULTS: We found that niosomes, which are liposomes containing a non-ionic surfactant, and transferosomes (ultraflexible vesicles) showed significantly greater penetration into the skin and permeation across the stratum corneum. Significant enhancement of caffeine penetration into hair follicles was found for transferosomes and those liposomes containing oleic acid. CONCLUSIONS: We conclude that targeted delivery of the hydrophilic drug caffeine into the skin compartments can be modified using optimized vesicular formulations. PMID- 26540489 TI - Genetic variations of Turkish bank vole, Myodes glareolus (Mammalia: Rodentia) inferred from mtDNA. AB - The bank vole, Myodes glareolus, lives in deciduous forests throughout the Palearctic region. In Turkey, this species is distributed only in northern Anatolia (the Black Sea region) where these forests exist. This study reveals genetic differentiation among bank vole populations based on two regions of mitochondrial DNA (cytochrome b and D-loop). Populations in northern Anatolia are divided into two genetic lineages (the "eastern" and "western Black Sea" lineages) by the Kizilirmak Valley. While the western Black Sea lineage is close to the Balkan lineage, in accordance with their geographical proximities, surprisingly, the Uludag lineage, also situated in Western Turkey appears related to the eastern Black Sea population. The divergence time analyses suggest a separation between the Balkan and Turkish groups around 0.26 Mya, whereas the split between the eastern and western Black sea lineages appeared a little bit later (0.20 Mya). Our results suggest that regional refuges existed for this species in Turkey and that small-scale habitat fragmentations led to genetic differentiations between Myodes populations. PMID- 26540488 TI - Localised hyperthermia in rodent models using an MRI-compatible high-intensity focused ultrasound system. AB - PURPOSE: Localised hyperthermia in rodent studies is challenging due to the small target size. This study describes the development and characterisation of an MRI compatible high-intensity focused ultrasound (HIFU) system to perform localised mild hyperthermia treatments in rodent models. MATERIAL AND METHODS: The hyperthermia platform consisted of an MRI-compatible small animal HIFU system, focused transducers with sector-vortex lenses, a custom-made receive coil, and means to maintain systemic temperatures of rodents. The system was integrated into a 3T MR imager. Control software was developed to acquire images, process temperature maps, and adjust output power using a proportional-integral derivative feedback control algorithm. Hyperthermia exposures were performed in tissue-mimicking phantoms and in a rodent model (n = 9). During heating, an ROI was assigned in the heated region for temperature control and the target temperature was 42 degrees C; 30 min mild hyperthermia treatment followed by a 10-min cooling procedure was performed on each animal. RESULTS: 3D-printed sector vortex lenses were successful at creating annular focal regions which enables customisation of the heating volume. Localised mild hyperthermia performed in rats produced a mean ROI temperature of 42.1 +/- 0.3 degrees C. The T10 and T90 percentiles were 43.2 +/- 0.4 degrees C and 41.0 +/- 0.3 degrees C, respectively. For a 30-min treatment, the mean time duration between 41-45 degrees C was 31.1 min within the ROI. CONCLUSIONS: The MRI-compatible HIFU system was successfully adapted to perform localised mild hyperthermia treatment in rodent models. A target temperature of 42 degrees C was well-maintained in a rat thigh model for 30 min. PMID- 26540490 TI - Photoinduced C-S Bond Cleavage of Thioglycosides and Glycosylation. AB - A glycosyl coupling reaction via photoinduced direct activation of thioglycosides and subsequent O-glycosylation in the absence of photosensitizer was developed for the first time. This reaction underwent a selectively homolytic cleavage of a C-S bond to generate a glycosyl radical, which was oxidized to an oxacarbenium ion by Cu(OTf)2, and a sequential O-glycosylation. A wide range of glycosides were synthesized in moderate to excellent yield using sugars, amino acids, or cholesterol as the acceptors. PMID- 26540491 TI - Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics: a post hoc analysis of the TIOSPIR trial. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. AIMS: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 MUg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 MUg. METHODS: A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. RESULTS: Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. CONCLUSIONS: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. PMID- 26540493 TI - Trastuzumab and Cardiac Outcomes in Breast Cancer: A Story We Know by Heart? PMID- 26540492 TI - Evaluation and management of spinal epidural abscess. AB - Spinal epidural abscess (SEA) is an uncommon and potentially catastrophic condition. SEA often presents a diagnostic challenge, as the "classic triad" of fever, spinal pain, and neurological deficit is evident in only a minority of patients. When diagnosis is delayed, irreversible neurological damage may ensue. To minimize morbidity, an appropriate level of suspicion and an understanding of the diagnostic evaluation are essential. Infection should be suspected in patients presenting with axial pain, fever, or elevated inflammatory markers. Although patients with no known risk factors can develop SEA, clinical concern should be heightened in the presence of diabetes, intravenous drug use, chronic renal failure, immunosuppressant therapy, or a recent invasive spine procedure. When the clinical profile is consistent with the diagnosis of SEA, gadolinium enhanced magnetic resonance imaging of the spinal column should be obtained on an emergent basis to delineate the location and neural compressive effect of the abscess. Rapid diagnosis allows for efficient treatment, which optimizes the potential for a positive outcome. PMID- 26540494 TI - Anti-HIV-1 activity of a tripodal receptor that recognizes mannose oligomers. AB - The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly alpha-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5 triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes alpha-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1. PMID- 26540495 TI - The Prevalence of Atopic Dermatitis in Korean Children. PMID- 26540496 TI - Update on Advances in Research on Idiosyncratic Drug-Induced Liver Injury. AB - Drug-induced liver injury (DILI) is a major concern for public health, as well as for drug development in the pharmaceutical industry, since it can cause liver failure and lead to drug withdrawal from the market and black box warnings. Thus, it is important to identify biomarkers for early prediction to increase our understanding of mechanisms underlying DILI that will ultimately aid in the exploration of novel therapeutic strategies to prevent or manage DILI. DILI can be subdivided into 'intrinsic' and 'idiosyncratic' categories, although the validity of this classification remains controversial. Idiosyncratic DILI occurs in a minority of susceptible individuals with a prolonged latency, while intrinsic DILI results from drug-induced direct hepatotoxicity over the course of a few days. The rare occurrence of idiosyncratic DILI requires multicenter collaborative investigations and phenotype standardization. Recent progress in research on idiosyncratic DILI is based on key developments in 3 areas: (1) newly developed high-throughput genotyping across the whole genome allowing for the identification of genetic susceptibility markers, (2) new mechanistic concepts on the pathogenesis of DILI revealing a key role of drug-responsive T lymphocytes in the immunological response, and (3) broad multidisciplinary approaches using different platform "-omics" technologies that have identified novel biomarkers for the prediction of DILI. An association of a specific human leukocyte antigen (HLA) allele with DILI has been reported for several drugs. HLA-restricted T-cell immune responses have also been investigated using lymphocytes and T-cell clones isolated from patients. A microRNA, miR-122, has been discovered as a promising biomarker for the early prediction of DILI. In this review, we summarize recent advances in research on idiosyncratic DILI with an understanding of the key role of adaptive immune systems. PMID- 26540497 TI - Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease. AB - Nitric oxide (NO) is endogenously released in the airways, and the fractional concentration of NO in exhaled breath (FeNO) is now recognized as a surrogate marker of eosinophilic airway inflammation that can be measured using a noninvasive technique suitable for young children. Although FeNO levels are affected by several factors, the most important clinical determinants of increased FeNO levels are atopy, asthma, and allergic rhinitis. In addition, air pollution is an environmental determinant of FeNO that may contribute to the high prevalence of allergic disease. In this review, we discuss the mechanism for airway NO production, methods for measuring FeNO, and determinants of FeNO in children, including host and environmental factors such as air pollution. We also discuss the clinical utility of FeNO in children with asthma and allergic rhinitis and further useful directions using FeNO measurement. PMID- 26540498 TI - Prevalence, Severity, and Treatment of Recurrent Wheezing During the First Year of Life: A Cross-Sectional Study of 12,405 Latin American Infants. AB - PURPOSE: This study aimed to determine the prevalence and severity of recurrent wheezing (RW) defined as >=3 episodes of wheezing, risk factors, and treatments prescribed during the first year of life in Latin American infants. METHODS: In this international, cross-sectional, and community-based study, parents of 12,405 infants from 11 centers in 6 South American countries (Argentina, Brazil, Chile, Colombia, Peru, and Uruguay) completed a questionnaire about wheezing and associated risk/protective factors, asthma medications, and the frequency of and indications for the prescription of antibiotics and paracetamol during the first year of life. RESULTS: The prevalence of RW was 16.6% (95% CI 16.0-17.3); of the 12,405 infants, 72.7% (95% CI 70.7-74.6) visited the Emergency Department for wheezing, and 29.7% (27.7-31.7) was admitted. Regarding treatment, 49.1% of RW infants received inhaled corticosteroids, 55.7% oral corticosteroids, 26.3% antileukotrienes, 22.9% antibiotics >=4 times mainly for common colds, wheezing, and pharyngitis, and 57.5% paracetamol >=4 times. Tobacco smoking during pregnancy, household income per month <1,000 USD, history of parental asthma, male gender, and nursery school attendance were significant risk factors for higher prevalence and severity of RW, whereas breast-feeding for at least 3 months was a significant protective factor. Pneumonia and admissions for pneumonia were significantly higher in infants with RW as compared to the whole sample (3.5-fold and 3.7-fold, respectively). CONCLUSIONS: RW affects 1.6 out of 10 infants during the first year of life, with a high prevalence of severe episodes, frequent visits to the Emergency Department, and frequent admissions for wheezing. Besides the elevated prescription of asthma medications, there is an excessive use of antibiotics and paracetamol in infants with RW and also in the whole sample, which is mainly related to common colds. PMID- 26540499 TI - GIS-based Association Between PM10 and Allergic Diseases in Seoul: Implications for Health and Environmental Policy. AB - PURPOSE: The role of PM10 in the development of allergic diseases remains controversial among epidemiological studies, partly due to the inability to control for spatial variations in large-scale risk factors. This study aims to investigate spatial correspondence between the level of PM10 and allergic diseases at the sub-district level in Seoul, Korea, in order to evaluate whether the impact of PM10 is observable and spatially varies across the subdistricts. METHODS: PM10 measurements at 25 monitoring stations in the city were interpolated to 424 sub-districts where annual inpatient and outpatient count data for 3 types of allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) were collected. We estimated multiple ordinary least square regression models to examine the association of the PM10 level with each of the allergic diseases, controlling for various sub-district level covariates. Geographically weighted regression (GWR) models were conducted to evaluate how the impact of PM10 varies across the sub-districts. RESULTS: PM10 was found to be a significant predictor of atopic dermatitis patient count (P<0.01), with greater association when spatially interpolated at the sub-district level. No significant effect of PM10 was observed on allergic rhinitis and asthma when socioeconomic factors were controlled for. GWR models revealed spatial variation of PM10 effects on atopic dermatitis across the sub-districts in Seoul. The relationship of PM10 levels to atopic dermatitis patient counts is found to be significant only in the Gangbuk region (P<0.01), along with other covariates including average land value, poverty rate, level of education and apartment rate (P<0.01). CONCLUSIONS: Our findings imply that PM10 effects on allergic diseases might not be consistent throughout Seoul. GIS-based spatial modeling techniques could play a role in evaluating spatial variation of air pollution impacts on allergic diseases at the sub-district level, which could provide valuable guidelines for environmental and public health policymakers. PMID- 26540500 TI - The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy. AB - PURPOSE: Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. METHODS: This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. RESULTS: Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. CONCLUSIONS: Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy. PMID- 26540501 TI - Relationship Between Allergic Rhinitis and Mental Health in the General Korean Adult Population. AB - PURPOSE: This study was conducted to evaluate the association between AR and mental health status in the general Korean adult population and to investigate the relative burden of AR on mental health using the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification. METHODS: A cross-sectional study was performed by using data from 11,154 individuals, 19 years old or older in the Korean National Health and Nutrition Examination Survey 2011-2012. Univariate analysis was conducted in the healthy AR groups with weighted prevalence of demographic characteristics, socioeconomic status, and comorbid diseases. Subanalysis that classified AR severity according to the ARIA classification was carried out to evaluate the relationship of AR severity with mental health. The odds ratios (ORs) for each component representing mental health status were estimated by multiple logistic regression analysis with confounder adjustment. RESULTS: Univariate analysis with the chi-square test after adjustment for age, sex, body mass index, smoking status, alcohol use status, and exercise status, components representing mental health status showed a linear relationship with the severity of AR according to the ARIA classification. Stress, depressive mood, suicidal thoughts, and psychological consultation factors were correlated with AR after adjustment for demographic characteristics and socioeconomic status. Even after adjustment for comorbid allergic diseases, the correlation remained significant with stress, depressive mood, and psychological consultation factors (OR [95% CI]; 1.227 [1.042, 1.445], 1.368 [1.095, 1.71], 1.804 [1.096, 2.969], respectively). CONCLUSIONS: Patients with AR appear to be at higher risk of mental disorders in the general Korean adult population. Moreover, persistent or severe AR was correlated with poor mental health. Therefore, better control of AR may be conducive to better mental health, and more attention should be paid to the psychological status of AR patients. PMID- 26540502 TI - Effect of Amino Acid Polymorphisms of House Dust Mite Der p 2 Variants on Allergic Sensitization. AB - PURPOSE: The sequence variations of the Der p 2 allergen of Dermatophagoides pteronyssinus diverge along 2 pathways with particular amino acid substitutions at positions 40,47,111, and 114. The environmental prevalence and IgE binding to Der p 2 variants differ among regions. To compare IgE binding to Der p 2 variants between sera from Bangkok, Thailand and Perth, Western Australia with different variants and to determine the variant-specificity of antibodies induced by vaccination with recombinant variants. METHODS: The structures of recombinant variants produced in yeast were compared by circular dichroism and 1 anilinonaphthalene 8-sulfonic acid staining of their lipid-binding cavity. Sera from subjects in Bangkok and Perth where different variants are found were compared by the affinity (IC50) of IgE cross-reactivity to different variants and by direct IgE binding. Mice were immunized with the variants Der p 2.0101 and Der p 2.0110, and their IgG binding to Der p 2.0103, 2.0104, and 2.0109 was measured. RESULTS: The secondary structures of the recombinant variants resembled the natural allergen but with differences in ANS binding. The IC50 of Der p 2.0101 required 7-fold higher concentrations to inhibit IgE binding to the high-IgE binding Der p 2.0104 than for homologous inhibition in sera from Bangkok where it is absent, while in sera from Perth that have both variants the IC50 was the same and low. Reciprocal results were obtained for Der p 2.0110 not found in Perth. Direct binding revealed that Der p 2.0104 was best for detecting IgE in both regions, followed by Der p 2.0101 with binding to other variants showing larger differences. Mouse anti-Der p 2.0101 antibodies had a high affinity of cross reactivity but bound poorly to other variants. CONCLUSIONS: The affinity of IgE antibody cross-reactivity, the direct IgE binding, and the specificities of antibodies induced by vaccination show that measures of allergic sensitization and therapeutic strategies could be optimized with knowledge of Der p 2 variants. PMID- 26540503 TI - Alternaria Induces Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2. AB - PURPOSE: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with markedly increased eosinophils, Th2-type lymphocytes, fibroblasts, and goblet cells. Fungi are commonly associated with airway inflammatory diseases, and thymic stromal lymphopoietin (TSLP) is important in the development of Th2 inflammatory responses. The aim of this study was to investigate the interaction between airborne fungi and nasal fibroblasts in TSLP mRNA and protein expression. METHODS: Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria and Aspergillus, respectively, for 48 hours, and TSLP mRNA and protein expressions were measured. The reverse transcriptase polymerase chain reaction was performed for the Toll-like receptor (TLR) mRNA expression of the nasal fibroblasts. To determine the role of TLR in the induction of TSLP, the fibroblasts were transfected with siRNA against TLR2 and TLR5. RESULTS: Alternaria induced TSLP mRNA and protein expression in both inferior turbinate and nasal polyp fibroblasts. The nasal polyp fibroblasts responded more strongly to the fungi. TLR2 and TLR5 mRNA expressions were significantly increased with fungal stimulation and TSLP production was significantly inhibited by siRNA against TLR2. CONCLUSIONS: The results of this study show that TSLP expression could be induced in nasal fibroblasts by exposure to Alternaria and that TLR2 may be involved in the process. The promotion of TSLP production in nasal fibroblasts by airborne fungi may facilitate the development or exacerbation of Th2-type nasal inflammation, especially in CRS with nasal polyps. PMID- 26540504 TI - Alternative Method for Primary Nasal Epithelial Cell Culture Using Intranasal Brushing and Feasibility for the Study of Epithelial Functions in Allergic Rhinitis. AB - PURPOSE: Although differentiated normal human nasal epithelial (NHNE) cells can be used to study the role of human nasal epithelium, there is a need for effective culture models of nasal epithelium in sinonasal disease status, including allergic rhinitis (AR). We aimed to examine the feasibility of intranasal brushing for culture of nasal epithelial cells in AR patients and to verify the hypothesis that allergic nasal epithelial (ARNE) cells differ in histologic and physiologic characteristics. METHODS: We established a system for isolating (via intranasal brushing) and culturing (with air-liquid interface, ALI) nasal epithelial cells from healthy volunteers (n=8) and AR patients (n=8). We used this system to compare the histologic findings and physiologic characteristics of NHNE and ARNE. RESULTS: The histology results showed that fully differentiated ALI culture was obtained at least 14 days after confluence and that both ciliated and secretory cells were well differentiated in ALI culture using nasal brushing. The histology results of ARNE culture were significantly different from NHNE. The number of ciliated cells was lower, and secretory cells were more dominant in ARNE cell culture compared to NHNE cells. We also observed, by electron microscopy, loose tight junctions and short cilia in cultured ARNE cells. In addition, the mRNA level of TSLP which was one of the epithelial-derived allergic cytokines was significantly higher, and the expressions of genes involved in ciliogenesis were lower in cultured ARNE cells without allergen stimulation. CONCLUSIONS: Our findings suggest that ALI culture of ARNE cells using intranasal brushing may be an alternative method for epithelial cell culture in AR patients and that cultured ARNE cells will be useful for in vitro studies of the mechanisms at play during AR because they maintain unique allergic characteristics. PMID- 26540505 TI - Prevalence of Atopic Dermatitis in Korean Children Based on Data From the 2008 2011 Korean National Health and Nutrition Examination Survey. AB - Population-based studies of atopic dermatitis (AD) in Korean children are lacking. Thus, the purpose of this study was to determine the prevalence, geographic distribution, and risk factors of AD in the Korean pediatric population. We examined AD prevalence using data from the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES), which was a cross sectional survey of 8,947 children up to age 18 throughout the country. Overall, 13.50% of children reported a diagnosis of AD. The age-standardized prevalence ranged from 9.13% to 17.67% between cities and provinces, with the highest prevalence-observed in many of the larger cities at low latitudes, as well as Jeju-do. After adjusting for confounders, high economic status was found to be a significant factor for predicting increased prevalence of AD, with an odds ratio of 1.35 (95% confidence interval of 1.02-1.79, P=0.0034). Urban living (odds ratio 1.24, 95% confidence interval of 1.00-1.53, P=0.0526) was also associated with a higher prevalence of AD. In this first large scale, nationwide study in Korean children, we found that the overall prevalence of AD depends on age, household income, and geographic distribution. PMID- 26540506 TI - Inflammation Markers and FEF25-75: A Relevant Link in Children With Asthma. PMID- 26540507 TI - Cow's Milk Allergy: the Relevance of IgE. PMID- 26540508 TI - The Hydrolysis of Diclofenac Esters: Synthetic Prodrug Building Blocks for Biodegradable Drug-Polymer Conjugates. AB - Degradation reactions on diclofenac-monoglycerides (3a,b), diclofenac-(p hydroxybenzoate)-2-monoglyceride (3c), diclofenac (1), and diclofenac lactam (4) were performed at 37 degrees C in isotonic buffer solutions (apparent pH range 1 8) containing varying concentrations of acetonitrile (ACN). The concentration remaining of each analyte was measured versus time. Diclofenac-monoglycerides and diclofenac-(p-hydroxybenzoate)-2-monoglyceride (3c) were both found to undergo facile and complete hydrolysis in pH 7.4 isotonic phosphate buffer/10% ACN. Under mildly acidic, neutral or alkaline conditions, diclofenac-(p-hydroxybenzoate)-2 monoglyceride (3c) had the fastest hydrolysis rate (t1/2 = 3.23 h at pH 7.4), with simultaneous formation of diclofenac lactam (4) and diclofenac (1). Diclofenac-monoglycerides (3a,b) hydrolyzed more slowly under the same conditions, to again yield both diclofenac (1) and diclofenac lactam (4). There was also transesterification of diclofenac-2-monoglyceride (3b) to its regioisomer, diclofenac-1-monoglyceride (3a) across the pH range. Diclofenac was shown to be stable in neutral or alkaline conditions but cyclized to form the lactam (4) in acidic conditions. Conversely, the lactam (4) was stable under acidic conditions but was converted to an unknown species under alkaline or neutral conditions. PMID- 26540509 TI - Life cycle assessment as development and decision support tool for wastewater resource recovery technology. AB - Life cycle assessment (LCA) has been increasingly used in the field of wastewater treatment where the focus has been to identify environmental trade-offs of current technologies. In a novel approach, we use LCA to support early stage research and development of a biochemical system for wastewater resource recovery. The freshwater and nutrient content of wastewater are recognized as potential valuable resources that can be recovered for beneficial reuse. Both recovery and reuse are intended to address existing environmental concerns, for example, water scarcity and use of non-renewable phosphorus. However, the resource recovery may come at the cost of unintended environmental impacts. One promising recovery system, referred to as TRENS, consists of an enhanced biological phosphorus removal and recovery system (EBP2R) connected to a photobioreactor. Based on a simulation of a full-scale nutrient and water recovery system in its potential operating environment, we assess the potential environmental impacts of such a system using the EASETECH model. In the simulation, recovered water and nutrients are used in scenarios of agricultural irrigation-fertilization and aquifer recharge. In these scenarios, TRENS reduces global warming up to 15% and marine eutrophication impacts up to 9% compared to conventional treatment. This is due to the recovery and reuse of nutrient resources, primarily nitrogen. The key environmental concerns obtained through the LCA are linked to increased human toxicity impacts from the chosen end use of wastewater recovery products. The toxicity impacts are from both heavy metals release associated with land application of recovered nutrients and production of AlCl3, which is required for advanced wastewater treatment prior to aquifer recharge. Perturbation analysis of the LCA pinpointed nutrient substitution and heavy metals content of algae biofertilizer as critical areas for further research if the performance of nutrient recovery systems such as TRENS is to be better characterized. Our study provides valuable feedback to the TRENS developers and identifies the importance of system expansion to include impacts outside the immediate nutrient recovery system itself. The study also show for the first time the successful evaluation of urban-to-agricultural water systems in EASETECH. PMID- 26540510 TI - 10-Year Overview of the Hospital-Based Prevalence and Treatment of Congenital Cataracts: The CCPMOH Experience. AB - A review of 6 years of hospitalization charts from Zhongshan Ophthalmic Center (ZOC) revealed that congenital cataracts (CC) accounted for 2.39% of all cataract in-patient cases and that the age at surgery was decreasing before the establishment of the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH) in December 2010. We aimed to investigate data from the 4 years (January 2011 to December 2014) following the establishment of the CCPMOH, compared, and combined with data from the previous study period (January 2005 to December 2010) to generate a 10-year overview of the hospital-based prevalence and treatment of CC. In the 4-year period after CCPMOH establishment, the prevalence of CC was 2.01% in all hospitalizations, and was 2.78% in all cataract in-patients. Most of the eligible CC in-patients (71%) lived in south China. The ratio of boys to girls was 1.42:1. Nearly 2/3 of the patients underwent cataract extraction with primary intraocular lens (IOL) implantation at a mean age of 78.40+/-51.45 months, and cataract extraction surgeries without IOL implantation were performed in the remaining 1/3 of patients at a mean age of 10.03+/-15.92 months. After CCPMOH establishment, an increased incidence of CC was revealed, and the CC in patients were younger than the patients in the previous period. The 10-year overview (2421 CC in-patients from 206630 hospitalizations) revealed upward trends in both the number and the prevalence of CC and a further reduction in age at surgery. In conclusion, the data from 4-year period after CCPMOH establishment and the 10-year overview showed upward trends in the hospital-based prevalence of CC cases and a further reduction in age at surgery, likely reflecting the effects of the CCPMOH establishment and providing useful information for further CC studies and a valuable foundation for the prevention and treatment of this cause of childhood blindness. PMID- 26540511 TI - A Euploid Line of Human Embryonic Stem Cells Derived from a 43,XX,dup(9q),+12, 14,-15,-18,-21 Embryo. AB - Aneuploid embryos diagnosed by FISH-based preimplantation genetic screening (PGS) have been shown to yield euploid lines of human embryonic stem cells (hESCs) with a relatively high frequency. Given that the diagnostic procedure is usually based on the analysis of 1-2 blastomeres of 5 to 10-cell cleavage-stage embryos, mosaicism has been a likely explanation for the phenomena. However, FISH-based PGS can have a significant rate of misdiagnosis, and therefore some of those lines may have been derived from euploid embryos misdiagnosed as aneuploid. More recently, coupling of trophectoderm (TE) biopsy at the blastocyst stage and array CGH lead to a more informative form of PGS. Here we describe the establishment of a new line of hESCs from an embryo with a 43,XX,dup(9q),+12,-14,-15,-18,-21 chromosomal content based on array-CGH of TE biopsy. We show that, despite the complex chromosomal abnormality, the corresponding hESC line BR-6 is euploid (46,XX). Single nucleotide polymorphism analysis showed that the embryo's missing chromosomes were not duplicated in BR-6, suggesting the existence of extensive mosaicism in the TE lineage. PMID- 26540512 TI - Cellular traffic cops: the interplay between lipids and proteins regulates vesicular formation, trafficking, and signaling in mammalian cells. AB - Protein secretion and vesicular trafficking in mammalian cells rely on several key lipids including sphingolipids, phospholipids, and neutral lipids crucial to protein processing and other intracellular events. Proteins interact with these lipids to alter the shape of lipid bilayer, thereby playing a pivotal role in cellular sorting. Although some efforts have elucidated the role of these components, extensive studies are needed to further decipher the protein-lipid interactions along with the effect of membrane curvature and rafts in sorting of proteins. The regulatory role of proteins in subcellular localization and metabolism of lipids also needs to be described. Recent studies on the role of lipid-protein interactions in modulating membrane shape, signal transduction, and vesicular trafficking are presented in this review. PMID- 26540516 TI - Intracellular accumulation of trehalose and glycogen in an extreme oligotroph, Rhodococcus erythropolis N9T-4. AB - An extreme oligotroph, Rhodococcus erythropolis N9T-4, showed intracellular accumulation of trehalose and glycogen under oligotrophic conditions. No trehalose accumulation was observed in cells grown on the rich medium. Deletion of the polyphosphate kinase genes enhanced the trehalose accumulation and decreases the intracellular glycogen contents, suggesting an oligotrophic relationship between among the metabolic pathways of trehalose, glycogen, and inorganic polyphosphate biosyntheses. PMID- 26540514 TI - Patterns of Circulating Fibroblast Growth Factor 21 in Subjects with and without Type 2 Diabetes. AB - BACKGROUND: Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM. METHODS: Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI>=25 kg/m2) or lean (BMI<25 kg/m2). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects. RESULTS: The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 +/-158.72 ng/L vs. 178.93+/-121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4+/-471.47 ng/L; NC: 883.13+/-561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05). CONCLUSIONS: These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21. PMID- 26540513 TI - Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell. AB - Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the expression of mitochondrial- and nuclear-encoded oxidative phosphorylation genes as well as mitochondrial stress defensive proteins (UCP1, SOD2). Such adaptation is placed in a canonical mitohormetic response that proceeds via mitochondrial reactive oxygen species ((mt)ROS) production and redistribution of FoxO1 transcription factor into nucleus. Nuclear FoxO1 ((n)FoxO1) mediates retrograde communication by inducing the expression of mitochondrial oxidative and stress defensive genes. Collectively, our findings describe an unusual white/beige fat cell response to nutrient availability highlighting another health-promoting mechanism of fasting. PMID- 26540517 TI - Understanding Intrinsic Light Absorption Properties of UiO-66 Frameworks: A Combined Theoretical and Experimental Study. AB - A combined theoretical and experimental study is performed in order to elucidate the effects of linker functional groups on the photoabsorption properties of UiO 66-X materials. This study, in which both mono- and difunctionalized linkers (with X = OH, NH2, or SH) are investigated, aims to obtain a more complete picture of the choice of functionalization. Static time-dependent density functional theory calculations combined with molecular dynamics simulations are performed on the linkers, and the results are compared to experimental UV/vis spectra in order to understand the electronic effects governing the absorption spectra. The disubstituted linkers show larger shifts than the monosubstituted variants, making them promising candidates for further study as photocatalysts. Next, the interaction between the linker and the inorganic part of the framework is theoretically investigated using a cluster model. The proposed ligand-to-metal charge transfer is theoretically observed and is influenced by the differences in functionalization. Finally, the computed electronic properties of the periodic UiO-66 materials reveal that the band gap can be altered by linker functionalization and ranges from 4.0 down to 2.2 eV. Study of the periodic density of states allows the band gap modulations of the framework to be explained in terms of a functionalization-induced band in the band gap of the original UiO-66 host. PMID- 26540519 TI - Nanomechanical characterization and molecular mechanism study of nanoparticle reinforced and cross-linked chitosan biopolymer. AB - Chitosan (CS) is a biomaterial that offers many sophisticated and innovative applications in the biomedical field owing to its excellent characteristics of biodegradability, biocompatibility and non-toxicity. However, very low mechanical properties of chitosan polymer impose restriction on its further development. Cross-linking and nanoparticle reinforcement are the two possible methods to improve the mechanical properties of chitosan films. In this research, these two methods are adopted individually by using tripolyphosphate as cross-linker and nano-hydroxyapatite as particle reinforcement. The nanomechanical characterizations under static loading conditions are performed on these modified chitosan films. It is observed that nanoparticle reinforcement provided necessary mechanical properties such as ductility and modulus. The mechanisms involved in improvement of mechanical properties due to particle reinforcement are studied by molecular dynamics (MD). Further, improvement in mechanical properties due to combination of particle reinforcement and cross-linking agent with chitosan is investigated. The stress relaxation behavior for all these types of films is characterized under dynamic loading conditions using dynamic mechanical analysis (nanoDMA) experiment. A viscoelastic solid like response is observed for all types of film with modulus relaxing by 3-6% of its initial value. A suitable generalized Maxwell model is fitted with the obtained viscoelastic response of these films. The response to nano-scratch behavior is also studied for particle reinforced composite films. PMID- 26540518 TI - Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques. AB - PURPOSE: Aiming to gain a detailed insight into the physiological mechanisms involved under extreme conditions, a group of experienced ultra-marathon runners, performing the mountain Tor des Geants(r) ultra-marathon: 330 km trail-run in Valle d'Aosta, 24000 m of positive and negative elevation changes, was monitored. ROS production rate, antioxidant capacity, oxidative damage and inflammation markers were assessed, adopting micro-invasive analytic techniques. METHODS: Forty-six male athletes (45.04+/-8.75 yr, 72.6+/-8.4 kg, 1.76+/-0.05 m) were tested. Capillary blood and urine were collected before (Pre-), in the middle (Middle-) and immediately after (Post-) Race. Samples were analyzed for: Reactive Oxygen Species (ROS) production by Electron Paramagnetic Resonance; Antioxidant Capacity by Electrochemistry; oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH dG; 8-isoprostane: 8-isoPGF2alpha) and nitric oxide metabolites by enzymatic assays; inflammatory biomarkers (plasma and urine interleukin-6: IL-6-P and IL-6 U) by enzyme-linked immunosorbent assays (ELISA); Creatinine and Neopterin by HPLC, hematologic (lactate, glucose and hematocrit) and urine parameters by standard analyses. RESULTS: Twenty-five athletes finished the race, while twenty one dropped out of it. A significant increase (Post-Race vs Pre) of the ROS production rate (2.20+/-0.27 vs 1.65+/-0.22 MUmol.min-1), oxidative damage biomarkers (8-OH-dG: 6.32+/-2.38 vs 4.16+/-1.25 ng.mg-1 Creatinine and 8 isoPGF2alpha: 1404.0+/-518.30 vs 822.51+/-448.91 pg.mg-1Creatinine), inflammatory state (IL-6-P: 66.42+/-36.92 vs 1.29+/-0.54 pg.mL-1 and IL-6-U: 1.33+/-0.56 vs 0.71+/-0.17 pg.mL1) and lactate production (+190%), associated with a decrease of both antioxidant capacity (-7%) and renal function (i.e. Creatinine level +76%) was found. CONCLUSIONS: The used micro-invasive analytic methods allowed us to perform most of them before, during and immediately after the race directly in the field, by passing the need of storing and transporting samples for further analysis. Considered altogether the investigated variables showed up that exhaustive and prolonged exercise not only promotes the generation of ROS but also induces oxidative stress, transient renal impairment and inflammation. PMID- 26540520 TI - Solvent Controlled Structural Transition of KI4K Self-Assemblies: from Nanotubes to Nanofibrils. AB - The structural modulation of peptide and protein assemblies under well-controlled conditions is of both fundamental and practical significance. In spite of extensive studies, it remains hugely challenging to tune the self-assembled nanostructures in a controllable manner because the self-assembly processes are dictated by various noncovalent interactions and their interplay. We report here how to manipulate the self-assembly of a designed, symmetric amphiphilic peptide (KI4K) via the solvent-controlled structural transition. Structural transition processes were carefully followed by the combination of transmission electronic microscopy (TEM), atomic force microscopy (AFM), circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), and small angle neutron scattering (SANS). The results show that the introduction of acetonitrile into water significantly affected the hydrophobic interactions among hydrophobic side chains while imposing little impact on the beta-sheet hydrogen bonding between peptide backbones. A structural transition occurred from nanotubes to helical/twisted ribbons and then to thin fibrils with the addition of acetonitrile due to the reduced hydrophobic interactions and the consequent weakening of the lateral stacking between KI4K beta-sheets. The increased intermolecular electrostatic repulsions among lysine side chain amino groups had little effect on the lateral stacking of KI4K beta-sheets due to the molecular symmetry. Complementary molecular dynamic (MD) simulations also indicated the solvation of acetonitrile molecules into the hydrophobic domains weakening the coherence between the neighboring sheets. PMID- 26540521 TI - [Euthanasia in Belgium - what about the mentally ill?]. PMID- 26540522 TI - [The future of psychiatry and psychiatrists]. PMID- 26540523 TI - [How many people in Germany are seriously mentally ill?]. AB - OBJECTIVE: Severe and chronic mental illness (SMI) is associated with complex care needs. Mental health care planning requires exact estimates of the number of SMI patients. METHODS: Systematic search for conceptual and epidemiological work on SMI prevalence (age group 18 - 65 years) in Medline, Embase and PsycInfo. RESULTS: To date there is no international consensus on the definition of severe mental illness, however, there are a number of international studies allowing an estimate for Germany. The number of those affected with a severe mental illness based on the present findings is estimated at 1% to 2% of adults between 18 and 65 years. This means, that in Germany, about 500,000 to 1 million people are in need for complex mental health care interventions. CONCLUSIONS: The numbers estimated may serve as a first orientation in the field. Further research on SMI prevalence is urgently needed in order to inform a more precise mental health care planning process for people with SMI in Germany. PMID- 26540524 TI - [Reports from the working group of executive physicians of psychiatric and psychotherapy clinics of general hospitals in Germany]. PMID- 26540525 TI - [Reports from the Federal Directors' Conference]. PMID- 26540526 TI - Assessment of in silico models for acute aquatic toxicity towards fish under REACH regulation. AB - We evaluated the performance of eight QSAR in silico modelling packages (ACD/ToxSuiteTM, ADMET PredictorTM, DEMETRA, ECOSAR, TerraQSARTM, Toxicity Estimation Software Tool, TOPKATTM and VEGA) for acute aquatic toxicity towards two species of fish: Fathead Minnow and Rainbow Trout. For the Fathead Minnow, we compared model predictions for 567 substances with the corresponding experimental values for 96-h median lethal concentrations (LC50). Some models gave good results, with r2 up to 0.85. We also classified the predictions of all the models into four toxicity classes defined by CLP. This permitted us to assess other parameters, such as the percentage of correct predictions for each class. Then we used a set of 351 substances with toxicity data towards Rainbow Trout (96-h LC50). In this case the predictability was unacceptable for all the in silico models. The calculated r2 gave poor correlations (<=0.53). Another analysis was performed according to chemical classes and for mode of action. In the first case, all the classes show a high percentage of correct predictions, in the second case only narcotics and polar narcotics were predicted with good confidence. The results indicate the possibility of using in silico methods to estimate aquatic toxicity within REACH regulation, after careful evaluation. PMID- 26540527 TI - Flexible engineering designs for urban water management in Lusaka, Zambia. AB - Urban water systems are often designed using deterministic single values as design parameters. Subsequently the different design alternatives are compared using a discounted cash flow analysis that assumes that all parameters remain as predicted for the entire project period. In reality the future is unknown and at best a possible range of values for design parameters can be estimated. A Monte Carlo simulation could then be used to calculate the expected Net Present Value of project alternatives, as well as so-called target curves (cumulative frequency distribution of possible Net Present Values). The same analysis could be done after flexibilities were incorporated in the design, either by using decision rules to decide about the moment of capacity increase, or by buying Real Options (in this case land) to cater for potential capacity increases in the future. This procedure was applied to a sanitation and wastewater treatment case in Lusaka, Zambia. It included various combinations of on-site anaerobic baffled reactors and off-site waste stabilisation ponds. For the case study, it was found that the expected net value of wastewater treatment systems can be increased by 35-60% by designing a small flexible system with Real Options, rather than a large inflexible system. PMID- 26540528 TI - Enzyme-linked immunosorbent assay for triclocarban in aquatic environments. AB - A sensitive, competitive indirect enzyme-linked immunosorbent assay (ELISA) was developed for the detection of triclocarban (TCC) in waters and sediments. Haptens were synthesized by derivatizing the paraposition of a phenyl moiety of TCC. The synthesized hapten was then coupled to bovine thyroglobulin to be used as an immunogen, based on which, a high affinity monoclonal antibody 4D5 was produced with the hybridoma technique. Under the optimized conditions, using the monoclonal antibody, excellent performances of the assay were obtained: satisfactory sensitivity (IC50 (50% inhibition concentration) value, 0.43 ng/mL; limit of detection, 0.05 ng/mL); good linear range (0.05-10 ng/mL); and satisfactory accuracy (recoveries 70.7-107% in waters; 74.8-98.3% in sediments). Furthermore, TCC was found with the concentration ranging from not detected to 422.12 ng/L in waters and from 6.68 ng/g to 78.67 ng/g in sediments in Yunliang River, Ancient Canal and Hongqiao Port in Zhenjiang City. In conclusion ELISA could be applied for monitoring TCC in aquatic environments. PMID- 26540529 TI - Considering microbial and aggregate heterogeneity in biofilm reactor models: how far do we need to go? AB - A model describing a given system should be as simple as possible - but not simpler. The appropriate level of complexity depends both on the type of system and on the intended use of the model. This paper addresses the critical question of which purposes justify increased complexity of biofilm (reactor) models. Additional model features compared to conventional models considered are: (1) the inclusion of microbial diversity, distinguishing between different species performing the same function; and (2) the distinction between flocs and granules in putatively granular sludge reactors. With a multispecies model considering interspecies diversity, it was demonstrated that a given macroscopic reactor performance does not necessarily reflect steady state conditions on the microscale. In a second case study, it was shown that the addition of a small level of flocs can have a significant impact on macroscale process performance and on microbial population and activity distributions in granular sludge reactors. It was concluded that increased complexity in biofilm models, concerning microbial diversity or mesoscale aggregate architecture, is likely more useful when the focus is on understanding fundamental microscale outputs, but under specific conditions, these additional model features can be critically informative for bulk reactor behavior prediction and general understanding. PMID- 26540530 TI - Study on mechanism of algal inactivation and pollution removal by Fe-ACF electro Fenton-like process. AB - Algae inactivation and algal metabolic pollutant removal of Chlorella and Duneliella salina from seawater by the Fe-ACF electro Fenton-like process has been studied. The experiments were conducted at neutral condition of pH 8.3 (raw water) and 6.2 to break through the limit of strong acidic conditions. Experimental results indicated that the Fe-ACF electro Fenton-like process has a good effect for algae inactivation and for pollutant removal in neutral conditions, and pH has no obvious effect for the inactivation of algae. At optimum conditions, the inactivation efficiency for algae could reach up to 98%. A pH of 8.3 is more favorable for pollutant removal. Under neutral pH conditions, the coupling effect of indirect oxidation of *OH, direct oxidation of free chlorine and coagulation and adsorption of ferric and ferrous hydroxy complexes in the electro Fenton-like process was achieved, and the coupling effect promotes the inactivation of algae and the removal of metabolic pollutants. PMID- 26540531 TI - Changes of toxic metals during biological stabilization and their potential ecological risk assessment. AB - With various disadvantages of pollution control technologies for toxic metal contaminated soil, we mixed contaminated soil with sludge for in situ composting to stabilize toxic metals, so plants are enriched to take up the toxic metals. When simulating the above, we added toxic metal solution into sewage sludge, and then composed it with steel slag to determine inhibition of the availability of toxic metals. When toxic metals were added into sludge, the potential ecological index and geoaccumulation index of Cd became high while Zn was low. Steel slag had an inhibited availability of Cd, and when the adjunction of steel slag was 7%, the availability of Cd was lowest. Steel slag promoted the availability of Zn, and when the adjunction of steel slag was 27%, the availability of Zn was highest. Results showed that during composting, with increasing steel slag, Cd stabilizing time was reached sooner but Zn stabilizing time was slower, and the availability of all metals became lower. In the end, composting inhibited the potential ecological index of Cd, but it promoted the potential ecological index of Zn. Steel slag promoted the stability of Cd and Zn as Fe/Mn oxide-bound and residual species. Therefore, composting sludge and steel slag could be used as an effective inhibitor of Zn and Cd pollution. PMID- 26540532 TI - Algae biomass cultivation in nitrogen rich biogas digestate. AB - Because microalgae are known for quick biomass growth and nutrient uptake, there has been much interest in their use in research on wastewater treatment methods. While many studies have concentrated on the algal treatment of wastewaters with low to medium ammonium concentrations, there are several liquid waste streams with high ammonium concentrations that microalgae could potentially treat. The aim of this paper was to test ammonium tolerance of the indigenous algae community of Lake Malaren and to use this mixed consortia of algae to remove nutrients from biogas digestate. Algae from Lake Malaren were cultivated in Jaworski's Medium containing a range of ammonium concentrations and the resulting algal growth was determined. The algae were able to grow at NH4-N concentrations of up to 200 mg L(-1) after which there was significant inhibition. To test the effectiveness of the lake water algae on the treatment of biogas digestate, different pre-cultivation set-ups and biogas digestate concentrations were tested. It was determined that mixing pre-cultivated suspension algae with 25% of biogas digestate by volume, resulting in an ammonium concentration of around 300 mg L(-1), produced the highest algal growth. The algae were effective in removing 72.8+/-2.2% of NH4-N and 41.4+/-41.4% of PO4-P. PMID- 26540534 TI - The cost of a small membrane bioreactor. AB - The individual cost contributions to the mechanical components of a small membrane bioreactor (MBR) (100-2,500 m3/d flow capacity) are itemised and collated to generate overall capital and operating costs (CAPEX and OPEX) as a function of size. The outcomes are compared to those from previously published detailed cost studies provided for both very small containerised plants (<40 m3/day capacity) and larger municipal plants (2,200-19,000 m3/d). Cost curves, as a function of flow capacity, determined for OPEX, CAPEX and net present value (NPV) based on the heuristic data used indicate a logarithmic function for OPEX and a power-based one for the CAPEX. OPEX correlations were in good quantitative agreement with those reported in the literature. Disparities in the calculated CAPEX trend compared with reported data were attributed to differences in assumptions concerning cost contributions. More reasonable agreement was obtained with the reported membrane separation component CAPEX data from published studies. The heuristic approach taken appears appropriate for small-scale MBRs with minimal costs associated with installation. An overall relationship of net present value=(a tb)Q(-c lnt+d) was determined for the net present value where a=1.265, b=0.44, c=0.00385 and d=0.868 according to the dataset employed for the analysis. PMID- 26540533 TI - Cross-sectoral optimization and visualization of transformation processes in urban water infrastructures in rural areas. AB - Predicted demographic, climatic and socio-economic changes will require adaptations of existing water supply and wastewater disposal systems. Especially in rural areas, these new challenges will affect the functionality of the present systems. This paper presents a joint interdisciplinary research project with the objective of developing an innovative software-based optimization and decision support system for the implementation of long-term transformations of existing infrastructures of water supply, wastewater and energy. The concept of the decision support and optimization tool is described and visualization methods for the presentation of results are illustrated. The model is tested in a rural case study region in the Southwest of Germany. A transformation strategy for a decentralized wastewater treatment concept and its visualization are presented for a model village. PMID- 26540535 TI - Physical design optimization of an urban runoff treatment system using Stormwater Management Model (SWMM). AB - The study presented the application of Stormwater Management Model (SWMM) in determining the optimal physical design properties of an established low impact development (LID) system treating road runoff. The calibration of the model was based on monitored storm events occurring from May 2010 to July 2013. It was found that the total suspended solids was highly correlated with stormwater runoff volume and dominant heavy metal constituents in stormwater runoff, such lead, zinc and copper, with a Pearson correlation coefficient ranging from 0.88 to 0.95 (P<0.05). Reducing the original ratio of the storage volume to surface area (SV/SA) of the facility and depth by 25% could match the satisfactory performance efficiency achieved in the original design. The smaller SV/SA and depth would mean a less costly system, signifying the importance of optimization in designing LID systems. PMID- 26540536 TI - Evaluating the application of Microbacterium sp. strain BR1 for the removal of sulfamethoxazole in full-scale membrane bioreactors. AB - Microbacterium sp. strain BR1 is a bacterial strain that recently received attention for its capability to mineralize sulfamethoxazole (SMX) and other sulfonamides. In this study, the survival of Microbacterium sp. in municipal sludge waters was tested in batch experiments to explore optimal process conditions. Inoculation of Microbacterium sp. was subsequently performed in a pilot membrane bioreactor (MBR) operated in two configurations: treating full scale MBR permeate (post-treatment) and treating raw municipal wastewater. SMX removal by Microbacterium sp. could not be proved in any of the configurations, except for SMX concentrations far higher than the ones normally found in municipal wastewater. By use of molecular tools (fluorescence in situ hybridization analysis) a low capability to survive in activated sludge systems was assessed. After inoculation, Microbacterium sp. was reduced to a small fraction of the viable biomass. The observed growth rate appeared to be many times lower than the one of typical activated sludge micro-organisms. Possibilities of application in full-scale municipal wastewater treatment are scarce. PMID- 26540537 TI - Dynamic simulation of water resources in an urban wetland based on coupled water quantity and water quality models. AB - Water quality in wetlands plays a huge role in maintaining the health of the wetland ecosystem. Water quality should be controlled by an appropriate water allocation policy for the protection of the wetlands. In this paper, models of rainfall/runoff, non-point source pollution load, water quantity/quality, and dynamic pollutant-carrying capacity were established to simulate the water quantity/quality of Xixi-wetland river network (in the Taihu basin, China). The simulation results showed a satisfactory agreement with field observations. Furthermore, a 'node-river-node' algorithm that adjusts to the 'Three Steps Method' was adopted to improve the dynamic pollutant-carrying capacity model and simulate the pollutant-carrying capacity in benchmark years. The simulation result shows that the water quality of the river network could reach class III stably all year round if the anthropogenic pollution is reduced to one-third of the current annual amount. Further investigation estimated the minimum amount of water diversion in benchmark years under the reasonable water quantity-regulating rule to keep water quality as class III. With comparison of the designed scale, the water diversion can be reduced by 184 million m3 for a dry year, 191 million m3 for a normal year, and 198 million m3 for a wet year. PMID- 26540538 TI - Cultivation of an Arthrospira platensis with digested piggery wastewater. AB - An Arthrospira platensis strain ZJWST-S1 was isolated in Jiaxing City, China, which proved able to proliferate quickly in undiluted digested piggery wastewater (DPW), and the protein content in the algal biomass was high. Single factor experiments showed that the strain was able to quickly grow in a Zarrouk medium as the dosage of sodium bicarbonate, nitrate-nitrogen and phosphate-phosphorus was not less than 4.0 mg.L(-1), 40 mg.L(-1) and 10 mg.L(-1), respectively. No growth inhibition was observed when the culturing medium contained nitrite nitrogen of 0-120 mg.L(-1) and ammonium nitrogen of below 20 mg.L(-1). Five runs of semi-continuous cultivation with DPW as the culturing medium in a 250 L raceway pond showed that the biomass yield in a 9-day semi-continuous culturing was up to 45.2-64.7 g.m(-2).d(-1), higher than the yields obtained by other researchers, and the crude protein content in biomass was over 50%, meeting the national animal feed grade standard. Total nitrogen (TN) and total phosphorus (TP) were removed from DPW at a rate of 10.9-14.0 mg.L(-1).d(-1) and 1.3-1.8 mg.L(-1).d(-1), respectively. The mass balance revealed that 80-93% of TN and 84 98% of TP reduced from DPW were converted to A. platensis biomass. PMID- 26540539 TI - Selective electrochemical detection of 2,4,6-trinitrotoluene (TNT) in water based on poly(styrene-co-acrylic acid) PSA/SiO2/Fe3O4/AuNPs/lignin-modified glassy carbon electrode. AB - A new versatile electrochemical sensor based on poly(styrene-co-acrylic acid) PSA/SiO2/Fe3O4/AuNPs/lignin (L-MMS) modified glassy carbon electrode (GCE) was developed for the selective detection of trace trinitrotoluene (TNT) from aqueous media with high sensitivity. The fabricated magnetic microspheres were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). L-MMS films were cast on the GCE surface to fabricate the TNT sensing electrode. The limit of detection (LOD) of TNT determined by the amperometric i-t curve reached 35 pM. The lignin film and well packed Fe3O4/AuNPs facilitated the pre-concentration of trace TNT on the electrode surface resulting in a fast amperometric response of 3 seconds near the detection limit. The high sensitivity and excellent catalytic activity of the modified electrode could be attributed to the lignin layer and highly packed Fe3O4/AuNPs on the electrode surface. The total recovery of TNT from tapwater and seawater matrices was 98% and 96%, respectively. The electrode film was highly stable after five repeated adsorption/desorption cycles. The new electrochemical sensing scheme provides a highly selective, sensitive and versatile assay for the in-situ detection of TNT in complex water media. PMID- 26540540 TI - Bayesian modeling of virus removal efficiency in wastewater treatment processes. AB - Left-censored datasets of virus density in wastewater samples make it difficult to evaluate the virus removal efficiency in wastewater treatment processes. In the present study, we modeled the probabilistic distribution of virus removal efficiency in a wastewater treatment process with a Bayesian approach, and investigated how many detect samples in influent and effluent are necessary for accurate estimation. One hundred left-censored data of virus density in wastewater (influent and effluent) were artificially generated based on assumed log-normal distributions and the posterior predictive distribution of virus density, and the log-ratio distribution were estimated. The estimation accuracy of distributions was quantified by Bhattacharyya coefficient. When it is assumed that the accurate estimation of posterior predictive distributions is possible when a 100% positive rate is obtained for 12 pairs of influent and effluent, 11 out of 144, 60 out of 324, and 201 out of 576 combinations of detect samples gave an accurate estimation at the significant level of 0.01 in a Kruskal-Wallis test when the total sample number was 12, 18, and 24, respectively. The combinations with the minimum number of detect samples were (12, 9), (16, 10), and (21, 8) when the total sample number was 12, 18, and 24, respectively. PMID- 26540541 TI - Malt house wastewater treatment with settleable algal-bacterial flocs. AB - This paper deals with biological treatment of malt house wastewater using algal bacterial flocs. During three months of testing, optimisation of growth conditions and biomass separation leads to maximisation of biomass production, improved flocs settleability and increased pollutant removal efficiency while maintaining low energy demand. At a high food to microorganism ratio (0.16 to 0.29 kg BOD5 kg(-1) TSS d(-1)), the biological oxygen demand (BOD5), chemical oxygen demand (CODCr), total phosphorus (Ptot) and total suspended solids (TSS) removal efficiencies were all higher than 90%. At a food to microorganism ratio of 0.06 kg BOD5 kg(-1) TSS d(-1), BOD5, CODCr, total nitrogen (Ntot), Ptot and TSS removal efficiencies of 99.5%, 97.6%, 91.5%, 97.8% and 98.4%, respectively, were achieved. The study also proved a strong dependence of removal efficiencies on solar radiation. The results suggest the algae-bacteria system is suitable for treatment of similar wastewater in locations with available land and sufficient solar radiation and temperature during the whole year. PMID- 26540542 TI - Effect of interaction between anionic surfactants and poly(piperazine-amide) nanofiltration membranes used for chromium(III) recovery from saline solution. AB - The effect of the anionic surfactant on the permeation properties of the nanofiltration (NF) membranes used for chromium(III) recovery from saline solution at low pH have been presented in this paper. The membrane surface layer performance periodically modified by sodium dodecyl sulphate (SDS) solution has been studied with measurements of zeta potential, atomic force microscopy (AFM) and permeability coefficient of tested membranes. It was found that the membrane surface layer modification by SDS caused a substantial reduction in the possibility of separation of loose NF membrane characterized by a high density of positively charged groups activating under the effect of the low pH of the saline solutions (HL membrane). On the other hand, in the case of dense NF membranes characterized by a strong negatively charged surface (DL membrane) constituting used the SDS improves the separation of chloride and chromium(III) ions. In this case, the surfactant solution also provides a high membrane permeability coefficient behavior over a long period of use. DL membrane modification by SDS allowed both to retain the stable membrane working for a long period and to limit the frequency of the chemical cleaning of this membrane. PMID- 26540543 TI - Validation of computational non-Newtonian fluid model for membrane bioreactor. AB - Membrane bioreactor (MBR) systems are often considered as the wastewater treatment method of the future due to their high effluent quality. One of the main problems with such systems is a relative large energy consumption, compared to conventional activated sludge (CAS) systems, which has led to further research in this specific area. A powerful tool for optimizing MBR-systems is computational fluid dynamics (CFD) modelling, which gives researchers the ability to describe the flow in the systems. A parameter which is often neglected in such models is the non-Newtonian properties of active sludge, which is of great importance for MBR systems since they operate at sludge concentrations up to a factor of 10 compared to CAS systems, resulting in strongly shear thinning liquids. A CFD-model is validated against measurements conducted in a system with rotating cross-flow membranes submerged in non-Newtonian liquids, where tangential velocities are measured with a Laser Doppler Anemometer (LDA). The CFD model is found to be capable of modelling the correct velocities in a range of setups, making CFD models a powerful tool for optimization of MBR systems. PMID- 26540544 TI - Preparation of N-doped ZnO-loaded halloysite nanotubes catalysts with high solar light photocatalytic activity. AB - N-doped ZnO nanoparticles were successfully assembled into hollow halloysite nanotubes (HNTs) by using the impregnation method. The catalysts based on N-doped ZnO-loaded HNTs nanocomposites (N-doped ZnO/HNTs) were characterized by X-ray diffraction (XRD), transmission electron microscopy-energy dispersive X-ray (TEM EDX), scanning electron microscopy-energy dispersive X-ray (SEM-EDX), UV-vis and Fourier transform infrared spectroscopy (FT-IR) techniques. The XRD pattern showed ZnO nanoparticles with hexagonal structure loaded on HNTs. The TEM-EDX analysis indicated ZnO particles with the crystal size of ca.10 nm scattered in hollow structure of HNTs, and furthermore the concentration of N atom in nanocomposites was up to 2.31%. The SEM-EDX verified most of N-ZnO nanoparticles existing in hollow nanotubes of HNTs. Besides containing an obvious ultraviolet absorbance band, the UV-vis spectra of the N-doped ZnO/HNTs catalysts showed an available visible absorbance band by comparing to HNTs and non-doped ZnO/HNTs. The photocatalytic activity of the N-doped ZnO/HNTs catalysts was evaluated by the degradation of methyl orange (MO) solution with the concentration of 20 mg/L under the simulated solar-light irradiation. The result showed that the N-doped ZnO/HNTs catalyst exhibited a desirable solar-light photocatalytic activity. PMID- 26540545 TI - Photodegradation of microcystin-LR catalyzed by metal phthalocyanines immobilized on TiO2-SiO2 under visible-light irradiation. AB - Microcystins (MCs) are a group of monocyclic heptapeptide toxins produced by species of cyanobacteria. Since MCs exhibit acute and chronic effects on humans and wildlife by damaging the liver, they are of increasing concern worldwide. In this study, we investigated the ability of the phthalocyanine compound (ZnPc-TiO2 SiO2) to degrade microcystin-LR (MC-LR) in the presence of visible light. X-ray diffraction (XRD) and UV-Visible diffuse reflectance spectra (UV-Vis DRS) were utilized to characterize the crystalline phase and the absorption behavior of this catalyst. According to the results, XRD spectra of ZnPc-TiO2-SiO2 powders taken in the 2theta configuration exhibited the peaks characteristic of the anatase phase. UV-Vis DRS showed that the absorption band wavelength shifted to the visible range when ZnPc was supported on the surface of TiO2-SiO2. Subsequently, several parameters including catalyst dose, MC-LR concentrations and pH were investigated. The MC-LR was quantified in each sample through high performance liquid chromatography (HPLC). The maximum MC-LR degradation rate of 80.2% can be obtained within 300 minutes under the following conditions: catalyst dose of 7.50 g/L, initial MC-LR concentration of 17.35 mg/L, pH 6.76 and the first cycling run of the photocatalytic reaction. Moreover, the degradation process fitted well with the pseudo-first-order kinetic model. PMID- 26540546 TI - Detection of boron removal capacities of different microorganisms in wastewater and effective removal process. AB - In this study boron removal capacities of different microorganisms were tested. Candida tropicalis, Rhodotorula mucilaginosa, Micrococcus luteus, Bacillus thuringiensis, Bacillus cereus, Bacillus megaterium, Bacillus pumilus, Pseudomonas aeruginosa and Aspergillus versicolor were examined for their boron bioaccumulation capacities in simulated municipal wastewater. A. versicolor and B. cereus were found as the most boron-tolerant microorganisms in the experiments. Also boron bioaccumulation yield of A. versicolor was 49.25% at 15 mg/L boron concentration. On the other hand biosorption experiments revealed that A. versicolor was more capable of boron removal in inactive form at the highest boron concentrations. In this paper maximum boron bioaccumulation yield was detected as 39.08% at 24.17 mg/L and the maximum boron biosorption yield was detected as 41.36% at 24.01 mg/L boron concentrations. PMID- 26540547 TI - Environmental performance of an integrated fixed-film activated sludge (IFAS) reactor treating actual municipal wastewater during start-up phase. AB - The present study summarizes the start-up performance and lessons learned during the start-up and optimization of a pilot-scale plant employing integrated fixed film activated sludge (IFAS) process treating actual municipal wastewater. A comprehensive start-up was tailored and implemented to cater for all the challenges and problems associated with start-up. After attaining desired suspended biomass (2,000-3,000 mg/L) and sludge age (~7 days), the average biological oxygen demand (BOD) and chemical oxygen demand (COD) removals were observed as 77.3 and 70.9%, respectively, at optimized conditions, i.e. hydraulic retention time (HRT), 6.9 h; return sludge rate, 160%. The influent concentrations of COD, BOD, total suspended solids, NH3-N, total nitrogen and total phosphorus were found to be in the range of 157-476 mg/L, 115-283 mg/L, 152 428 mg/L, 23.2-49.3 mg/L, 30.1-52 mg/L and 3.6-7.8 mg/L, respectively, and the minimum effluent concentrations were achieved as ~49 mg/L, 23 mg/L, 35 mg/L, 2.2 mg/L, 3.4 mg/L and 2.8 mg/L, respectively, at optimum state. The present system was found effective in the removal of pathogenic bacteria (Escherichia coli, 79%; Salmonella spp., 97.5%; Shigella spp., 92.9%) as well as coliforms (total coliforms, 97.65%; faecal coliforms, 80.35%) without any disinfection unit. Moreover it was observed that the time required for the stabilization of the plant was approximately 3 weeks if other parameters (sludge age, HRT and dissolved oxygen) are set to optimized values. PMID- 26540548 TI - Groundwater and stream E. coli concentrations in coastal plain watersheds served by onsite wastewater and a municipal sewer treatment system. AB - The goal of this study was to determine if onsite wastewater treatment systems (OWS) were influencing groundwater and surface water Escherichia coli concentrations in a coastal plain watershed. Piezometers for groundwater monitoring were installed at four residences served by OWS and five residences served by a municipal wastewater treatment system (MWS). The residences were located in two different, but nearby (<3 km), watersheds. Effluent from the four septic tanks, groundwater from piezometers, and the streams draining the OWS and MWS watersheds were sampled on five dates between September 2011 and May 2012. Groundwater E. coli concentrations and specific conductivity were elevated within the flow path of the OWS and near the stream, relative to other groundwater sampling locations in the two watersheds. Groundwater discharge in the OWS watershed could be a contributor of E. coli to the stream because E. coli concentrations in groundwater at the stream bank and in the stream were similar. Stream E. coli concentrations were higher for the OWS in relation to MWS watersheds on each sampling date. Water quality could be improved by ensuring OWS are installed and operated to maintain adequate separation distances to water resources. PMID- 26540549 TI - Adsorption of sunset yellow FCF from aqueous solution by chitosan-modified diatomite. AB - Sunset yellow (SY) FCF is a hazardous azo dye pollutant found in food processing effluent. This study investigates the use of diatomaceous earth with chitosan (DE@C) as a modified adsorbent for the removal of SY from wastewater. Fourier transform infrared spectroscopy results indicate the importance of functional groups during the adsorption of SY. The obtained N2 adsorption-desorption isotherm values accord well with IUPAC type II. Our calculations determined a surface area of 69.68 m2 g(-1) for DE@C and an average pore diameter of 4.85 nm. Using response surface methodology, optimized conditions of process variables for dye adsorption were achieved. For the adsorption of SY onto DE@C, this study establishes mathematical models for the optimization of pH, contact time and initial dye concentration. Contact time plays a greater role in the adsorption process than either pH or initial dye concentration. According to the adjusted correlation coefficient (adj-R2>0.97), the models used here are suitable for illustration of the adsorption process. Theoretical experimental conditions included a pH of 2.40, initial dye concentration of 113 mg L(-1) and 30.37 minutes of contact time. Experimental values for the adsorption rate (92.54%) were close to the values predicted by the models (95.29%). PMID- 26540550 TI - Use of the ferrates (FeIV-VI) in combination with hydrogen peroxide for rapid and effective remediation of water--laboratory and pilot study. AB - In recent years, particles of iron in higher oxidation states (Fe(IV-VI)), commonly called ferrates, have been presented theoretically as very effective oxidants. They can potentially be used for elimination of a wide range of organic and inorganic contaminants. However, so far the majority of applications have been carried out only as laboratory tests using model samples in many cases. The application of ferrates in remediation programs has so far proved to be more complicated with results failing to meet expectations. Therefore there is a necessity to consider the suitability of their use or consider their possible combination with other agents in order to reach required removal efficiencies in remediation. This study is focused on laboratory experiments using industrial groundwater leading to the proposal of a pilot field application realized as an ex-situ remediation. The combination of ferrates with hydrogen peroxide was used in this study in order to enhance the removal efficiency during pilot remediation of groundwater strongly contaminated by a wide range of organic contaminants. This combination has been shown to be very effective. During the 24-hour reaction time the majority of detected contaminants were removed by approximately 60-80%. Moreover, the unpleasant odor of the water was suppressed and suspended particles were removed by the flocculation effect of ferric sludge. PMID- 26540551 TI - An inexact multi-objective programming model for water resources management in industrial parks of Binhai New Area, China. AB - In recent years, Binhai New Area of Tianjin has been suffering severe water shortage due to climate change and industrial activities. Integrated and effective water resources management approaches are urgent for the sustainable development of industrial parks in Binhai New Area. However, uncertainties exist in many aspects of the water resources system and are inevitably problematic for water resources planning and policy-making. To address these uncertainties, an interval multiple-objective programming model was developed here to support the long-term planning of industrial water resources management in Binhai New Area, Tianjin, China. The model incorporated both multiple-objective programming and interval linear programming into a general programming framework. The developed model could handle the uncertainties and complexities of the water management system, and also allowed decision makers to adjust fuzzy objective control decision variables to satisfy multiple holistic and interactive objectives. The solutions are useful for planning adjustments of the existing water allocation patterns in Binhai New Area. PMID- 26540552 TI - Correction: Hydronephrotic Urine in the Obstructed Kidney Promotes Urothelial Carcinoma Cell Proliferation, Migration, Invasion through the Activation of mTORC2-AKT and ERK Signaling Pathways. PMID- 26540553 TI - The Effects of Age and Preoral Sensorimotor Cues on Anticipatory Mouth Movement During Swallowing. AB - PURPOSE: The aim of this study was to investigate the effects of preoral sensorimotor cues on anticipatory swallowing/eating-related mouth movements in older and younger adults. It was hypothesized that these cues are essential to timing anticipatory oral motor patterns, and these movements are delayed in older as compared with younger adults. METHOD: Using a 2 * 2 repeated-measures design, eating-related lip, jaw, and hand movements were recorded from 24 healthy older (ages 70-85 years) and 24 healthy younger (ages 18-30 years) adults under 4 conditions: typical self-feeding, typical assisted feeding (proprioceptive loss), sensory-loss self-feeding (auditory and visual loss/degradation), and sensory loss assisted feeding (loss/degradation of all cues). RESULTS: All participants demonstrated anticipatory mouth opening. The absence of proprioception delayed lip-lowering onset, and sensory loss more negatively affected offset. Given at least 1 preoral sensorimotor cue, older adults initiated movement earlier than younger adults. CONCLUSIONS: Preoral sensorimotor information influences anticipatory swallowing/eating-related mouth movements, highlighting the importance of these cues. Earlier movement in older adults may be a compensation, facilitating safe swallowing given other age-related declines. Further research is needed to determine if the negative impact of cue removal may be further exacerbated in a nonhealthy system (e.g., presence of dysphagia or disease), potentially increasing swallowing- and eating-related risks. PMID- 26540554 TI - Immediate Intraocular Pressure Changes Following Intravitreal Dexamethasone Implant. AB - PURPOSE: To evaluate the immediate intraocular pressure (IOP) changes following intravitreal dexamethasone implantation. METHODS: Thirty-four eyes of 34 consecutive patients (16 females and 18 males; mean age, 59.9 +/- 9.0 years) with diagnosis of macular edema secondary to diabetic retinopathy (20 eyes) or retinal vein occlusion (14 eyes) scheduled for intravitreal dexamethasone implantation (Ozurdex) were included in the study. IOP at baseline, minute 1, minute 10, hour 1, and day 1 was measured using Tono-Pen XL. As a subgroup, the eyes with visible reflux after the implantation were analyzed separately for IOP change. RESULTS: Overall, the only significant change in relation to baseline was observed immediately after the implantation (16.5 +/- 3.4 mmHg at baseline vs. 13.5 +/- 5.7 mmHg at minute 1, P = 0.004). In eyes with reflux (N = 9), the mean IOP was 15.4 +/- 2.4, 6.3 +/- 4.2, 10.1 +/- 4.4, 15.8 +/- 2.9, and 15.6 +/- 2.2 mmHg at baseline, minute 1, minute 10, hour 1, and day 1, respectively. The mean IOP was significantly lower at minute 1 (P = 0.008) and minute 10 (P = 0.013). In eyes without reflux (N = 25), the mean IOP was not significantly altered at any time point (for all P > 0.05). The rate of hypotony (IOP <6 mmHg) at minute 1, minute 10, hour 1, and day 1 was 8.8%, 2.9%, 0%, and 0%, respectively. Wound leakage and choroidal detachment were not observed in any of the eyes. CONCLUSIONS: The injection procedure of the Ozurdex implant itself does not affect IOP, except in the case of observable reflux, in which case the IOP temporarily decreases. PMID- 26540555 TI - Serum 25-Hydroxyvitamin D and Osteoarthritis in Older People: The Progetto Veneto Anziani Study. AB - Recent work has shown that low 25-hydroxyvitamin D (25OHD) levels are associated with the presence of osteoarthritis (OA), but these studies focused on radiographical changes of OA, investigated only one joint, and did not consider the association with OA-related pain. In this study, we aimed to examine the relationship between 25OHD levels and any presence of OA and pain in a cohort of older people. This study was part of the Progetto Veneto Anziani (Pro.V.A), a population-based cohort study in older people. In this cross-sectional work, we considered 2756 subjects (1102 males and 1654 females) with a mean age of 74.2 +/ 7.1 years. OA and OA-related pain were defined using a standardized algorithm investigating disease history, medical documentation, symptoms, and physical examination of the joints. On logistic regression analysis, taking those in the highest 25OHD quartile for reference, those in the lowest quartile had significantly higher odds of OA involving the hands (odds ratio [OR] = 1.26, 95% confidence interval [CI] 1.15-1.38 in the sample as whole; 1.36, 95% CI 1.15-1.60 in men and 1.22, 95% CI 1.09-1.37 in women), and pain (OR = 1.18, 95% CI 1.06 1.32 in the sample as whole; 1.52, 95% CI 1.21-1.90 in men and 1.15, 95% CI 1.03 1.29 in women). Similar results were found for the hip. For the knee, low 25OHD levels were associated with the presence of OA in the sample as a whole, and in women, and with the presence of pain in the sample as a whole. In conclusion, low 25OHD levels are associated with the presence of OA and with OA-related pain, particularly when the hand and hip are involved. PMID- 26540556 TI - The CD68(+)/H-ferritin(+) cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular level of H-ferritin in the same tissue: correlation with disease severity and implication for pathogenesis. AB - In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult-onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H-ferritin and L-ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possible correlation among the number of CD68(+)/H-ferritin(+) or CD68(+)/L-ferritin(+) cells and the clinical picture. Immunofluorescence analysis demonstrated an increased tissue H ferritin expression in the LNs of AOSD patients. This increased expression correlated with the severity of the disease. An increased number of CD68 macrophages expressing H-ferritin was observed in the LN samples of our patients. Furthermore, we observed that the number of CD68(+)/H-ferritin(+) cells correlated significantly with the severity of the clinical picture. Our data showed an imbalance between the levels of H- and L-ferritin in LNs of AOSD patients and the evidence of an increased number of CD68(+)/H-ferritin(+) cells in the same organs. Furthermore, a correlation among both the tissue H-ferritin levels and the CD68(+)/H-ferritin(+) cells and the clinical picture was observed. PMID- 26540557 TI - Versatile Cellulose-Based Carbon Aerogel for the Removal of Both Cationic and Anionic Metal Contaminants from Water. AB - Hydrothermal carbonization of cellulose in the presence of the globular protein ovalbumin leads to the formation of nitrogen-doped carbon aerogel with a fibrillar continuous carbon network. The protein plays here a double role: (i) a natural source of nitrogen functionalities (2.1 wt %) and (ii) structural directing agent (S(BET) = 38 m(2)/g). The applicability in wastewater treatment, namely, for heavy metal removal, was examined through adsorption of Cr(VI) and Pb(II) ion solely and in a mixed bicomponent aqueous solutions. This cellulose based carbogel shows an enhanced ability to remove both Cr(VI) (~68 mg/g) and Pb(II) (~240 mg/g) from the targeted solutions in comparison to other carbon materials reported in the literature. The presence of competing ions showed little effect on the adsorption efficiency toward Cr(VI) and Pb(II). PMID- 26540559 TI - The National Academy of Medicine's Vision: Leadership, Innovation, and Impact for a Healthier Future. PMID- 26540558 TI - Au25 cluster functionalized metal-organic nanostructures for magnetically targeted photodynamic/photothermal therapy triggered by single wavelength 808 nm near-infrared light. AB - Near-infrared (NIR) light-induced cancer therapy has gained considerable interest, but pure inorganic anti-cancer platforms usually suffer from degradation issues. Here, we designed metal-organic frameworks (MOFs) of Fe3O4/ZIF-8-Au25 (IZA) nanospheres through a green and economic procedure. The encapsulated Fe3O4 nanocrystals not only produce hyperthemal effects upon NIR light irradiation to effectively kill tumor cells, but also present targeting and MRI imaging capability. More importantly, the attached ultrasmall Au25(SR)18(-) clusters (about 2.5 nm) produce highly reactive singlet oxygen ((1)O2) to cause photodynamic effects through direct sensitization under NIR light irradiation. Furthermore, the Au25(SR)18(-) clusters also give a hand to the hyperthemal effect as photothermal fortifiers. This nanoplatform exhibits high biocompatibility and an enhanced synergistic therapeutic effect superior to any single therapy, as verified by in vitro and in vivo assay. This image-guided therapy based on a metal-organic framework may stimulate interest in developing other kinds of metal-organic materials with multifunctionality for tumor diagnosis and therapy. PMID- 26540560 TI - A Novel Method to Predict Highly Expressed Genes Based on Radius Clustering and Relative Synonymous Codon Usage. AB - Recombinant proteins play an important role in many aspects of life and have generated a huge income, notably in the industrial enzyme business. A gene is introduced into a vector and expressed in a host organism-for example, E. coli-to obtain a high productivity of target protein. However, transferred genes from particular organisms are not usually compatible with the host's expression system because of various reasons, for example, codon usage bias, GC content, repetitive sequences, and secondary structure. The solution is developing programs to optimize for designing a nucleotide sequence whose origin is from peptide sequences using properties of highly expressed genes (HEGs) of the host organism. Existing data of HEGs determined by practical and computer-based methods do not satisfy for qualifying and quantifying. Therefore, the demand for developing a new HEG prediction method is critical. We proposed a new method for predicting HEGs and criteria to evaluate gene optimization. Codon usage bias was weighted by amplifying the difference between HEGs and non-highly expressed genes (non-HEGs). The number of predicted HEGs is 5% of the genome. In comparison with Puigbo's method, the result is twice as good as Puigbo's one, in kernel ratio and kernel sensitivity. Concerning transcription/translation factor proteins (TF), the proposed method gives low TF sensitivity, while Puigbo's method gives moderate one. In summary, the results indicated that the proposed method can be a good optional applying method to predict optimized genes for particular organisms, and we generated an HEG database for further researches in gene design. PMID- 26540561 TI - Looking Upstream: Findings from Focus Groups on Public Perceptions of Source Water Quality in British Columbia, Canada. AB - In association with the development of new microbial tests for source water quality (SWQ), focus groups with members of the public were conducted to gain insight into their perceptions of SWQ, behaviours and contaminants they think pose the greatest threat to its quality, and what/how they want to know about SWQ. Discussions revealed a low concern about SWQ in general, and in particular about microbial contamination. Participants identified behaviours that threaten SWQ, barriers to changing behaviour and suggestions for inducing change. A strong desire was expressed for water quality information to be interpreted and communicated in terms of how SWQ may impact human health and how their actions should be altered in response to test results. The information can be used to inform communication strategies and possibly impact policies associated with water quality testing and implementation of new tests. More broadly, awareness of the public's understanding and beliefs about source water can be used in working with the public to adopt water-friendly behaviours, influence the content and methods of communicating with the public about water issues and water quality, and could contribute to the direction of future research and investment into water technologies to align with the public's priorities. PMID- 26540562 TI - Defining Vitamin D Deficiency and Its Relationship to Hypertension in Postmenopausal Korean Women. AB - BACKGROUND: Inconsistent results regarding the association between low vitamin D level and hypertension (HTN) have led to uncertainty in clinical practice as to the use of vitamin D cutoff value. The aims of this study were to investigate the association between vitamin D deficiency and HTN in postmenopausal women and to determine the clinically significant cutoff value for vitamin D deficiency. METHODS: We analyzed data from the Korean National Health and Nutrition Examination Survey 5 database (4107 postmenopausal women, aged 50-79 years). The cutoff value for vitamin D deficiency was based on the changes in parathyroid hormone (PTH) level according to serum 25(OH)D value. RESULTS: PTH levels were significantly higher in groups with serum 25(OH)D <15 ng/mL (p < 0.001). When a serum 25(OH)D value of 15 ng/mL was used as a cutoff value, 35.2% of the subjects were found to be vitamin D deficient. Although the association between 25(OH)D level <15 ng/mL and systolic blood pressure did not remain significant after adjusting for season (p = 0.30), multiple logistic regression analysis revealed that 25(OH)D level <15 ng/mL was an independent risk factor for HTN (adjusted odds ratio [OR] 1.285, 95% confidence interval [CI] 1.024-1.614, p = 0.031). CONCLUSIONS: Using serum PTH level, we defined vitamin D deficiency as 25(OH)D <15 ng/mL in postmenopausal women. Vitamin D deficiency [25(OH)D <15 ng/mL] was a significant risk factor for HTN in postmenopausal women. PMID- 26540563 TI - Biodegradation of direct blue 129 diazo dye by Spirodela polyrrhiza: An artificial neural networks modeling. AB - Phytoremediation potential of the aquatic plant Spirodela polyrrhiza was examined for direct blue 129 (DB129) azo dye. The dye removal efficiency was optimized under the variable conditions of the operational parameters including removal time, initial dye concentration, pH, temperature and amount of plant. The study reflected the significantly enhanced dye removal efficiency of S. polyrrhiza by increasing the temperature, initial dye concentration and amount of plant. Intriguingly, artificial neural network (ANN) predicted the removal time as the most dominant parameter on DB129 removal efficiency. Furthermore, the effect of dye treatment on some physiologic indices of S. polyrrhiza including growth rate, photosynthetic pigments content, lipid peroxidation and antioxidant enzymes were studied. The results revealed a reduction in photosynthetic pigments content and in multiplication of fronds after exposure to dye solution. In contrast, malondialdehyde content as well as catalase (CAT) and peroxidase (POD) activities significantly increased that was probably due to the ability of plant to overcome oxidative stress. As a result of DB129 biodegradation, a number of intermediate compounds were identified by gas chromatography-mass spectroscopy (GC-MS) analysis. Accordingly, the probable degradation pathway of DB129 in S. polyrrhiza was postulated. PMID- 26540564 TI - Discovery of N-[5-(6-Chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl] ethanesulfonamide, a Cortisol-Sparing CYP11B2 Inhibitor that Lowers Aldosterone in Human Subjects. AB - Human clinical studies conducted with LCI699 established aldosterone synthase (CYP11B2) inhibition as a promising novel mechanism to lower arterial blood pressure. However, LCI699's low CYP11B1/CYP11B2 selectivity resulted in blunting of adrenocorticotropic hormone-stimulated cortisol secretion. This property of LCI699 prompted its development in Cushing's disease, but limited more extensive clinical studies in hypertensive populations, and provided an impetus for the search for cortisol-sparing CYP11B2 inhibitors. This paper summarizes the discovery, pharmacokinetics, and pharmacodynamic data in preclinical species and human subjects of the selective CYP11B2 inhibitor 8. PMID- 26540565 TI - High-throughput identification of protein mutant stability computed from a double mutant fitness landscape. AB - The effect of a mutation on protein stability is traditionally measured by genetic construction, expression, purification, and physical analysis using low throughput methods. This process is tedious and limits the number of mutants able to be examined in a single study. In contrast, functional fitness effects can be measured in a high-throughput manner by various deep mutational scanning tools. Using protein GB 1, we have recently demonstrated the feasibility of estimating the mutational stability effect ( DeltaDeltaG) of single-substitution based on the functional fitness profile of all double-substitutions. The principle is to identify genetic backgrounds that have an exhausted stability margin. The functional effect of an additional substitution on these genetic backgrounds can then be used to compute the mutational DeltaDeltaG based on the biophysical relationship between functional fitness and thermodynamic stability. However, to identify such genetic backgrounds, the approach described in our previous study required a benchmark dataset, which is a set of known mutational DeltaDeltaG. In this study, a benchmark-independent approach is developed. The genetic backgrounds of interest are identified using k-means clustering with the integration of structural information. We further demonstrated that a reasonable approximation of DeltaDeltaG can also be obtained without taking structural information into account. In summary, this study describes a novel method for computing DeltaDeltaG from double-substitution functional fitness profiles alone, without relying on any known mutational DeltaDeltaG as a benchmark. PMID- 26540566 TI - Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications. AB - Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A- expression had the worst prognosis while the patient group with PARP1-/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 * 10(-9), RFS: P = 2.2 * 10(-8)). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. PMID- 26540567 TI - Bone marrow stroma-induced resistance of chronic lymphocytic leukemia cells to arsenic trioxide involves Mcl-1 upregulation and is overcome by inhibiting the PI3Kdelta or PKCbeta signaling pathways. AB - CLL remains an incurable disease in spite of the many new compounds being studied. Arsenic trioxide (ATO) induces apoptosis in all CLL cell types and could constitute an efficient therapy. To further explore this, we have studied the influence of stromal cells, key components of the CLL microenvironment, on the response of CLL cells to ATO. Bone marrow stromal cells induced CLL cell resistance to 2 MUM ATO and led to activation of Lyn, ERK, PI3K and PKC, as well as NF-kappaB and STAT3. Mcl-1, Bcl-xL, and Bfl-1 were also upregulated after the co-culture. Inhibition experiments indicated that PI3K and PKC were involved in the resistance to ATO induced by stroma. Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kdelta and PKCbeta, respectively, inhibited Akt phosphorylation, NF-kappaB/STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO. Mcl-1 was central to the mechanism of resistance to ATO, since: 1) Mcl-1 levels correlated with the CLL cell response to ATO, and 2) blocking Mcl-1 expression or function with specific siRNAs or inhibitors overcame the protecting effect of stroma. We have therefore identified the mechanism involved in the CLL cell resistance to ATO induced by bone marrow stroma and show that idelalisib or sotrastaurin block this mechanism and restore sensibility to ATO. Combination of ATO with these inhibitors may thus constitute an efficient treatment for CLL. PMID- 26540568 TI - Invasive oral cancer stem cells display resistance to ionising radiation. AB - There is a significant amount of evidence to suggest that human tumors are driven and maintained by a sub-population of cells, known as cancer stem cells (CSC). In the case of head and neck cancer, such cells have been characterised by high expression levels of CD44 cell surface glycoprotein, while we have previously shown the presence of two diverse oral CSC populations in vitro, with different capacities for cell migration and proliferation. Here, we examined the response of oral CSC populations to ionising radiation (IR), a front-line measure for the treatment of head and neck tumors. We show that oral CSC initially display resistance to IR-induced growth arrest as well as relative apoptotic resistance. We propose that this is a result of preferential activation of the DNA damagerepair pathway in oral CSC with increased activation of ATM and BRCA1, elevated levels of DNA repair proteins RAD52, XLF, and a significantly faster rate of DNA double-strand-breaks clearance 24 hours following IR. By visually identifying CSC sub-populations undergoing EMT, we show that EMT-CSC represent the majority of invasive cells, and are more radio-resistant than any other population in re-constructed 3D tissues. We provide evidence that IR is not sufficient to eliminate CSC in vitro, and that sensitization of CD44hi/ESAlow cells to IR, followed by secondary EMT blockade, could be critical in order to reduce primary tumor recurrence, but more importantly to be able to eradicate cells capable of invasion and distant metastasis. PMID- 26540570 TI - Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma. AB - Survival of activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL) is driven by chronic B cell receptor (BCR) signaling that activates the canonical NF-kappaB pathway. Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79. However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant. Therefore, we assessed here the simultaneous inhibition of BTK and the protease MALT1 that acts downstream of CARMA1 and is essential for ABC DLBCL tumor growth. We show that in CD79 mutant cells BTK is a crucial upstream regulator of MALT1, but dispensable in CARMA1 mutant ABC DLBCL. Combined inhibition of BTK by Ibrutinib and MALT1 by S-Mepazine additively impaired MALT1 cleavage activity and expression of NF-kappaB pro survival factors. Thereby, combinatorial Ibrutinib and S-Mepazine treatment enhanced killing of CD79 mutant ABC DLBCL cells. Moreover, while expression of oncogenic CARMA1 in CD79 mutant cells conferred Ibrutinib resistance, double mutant cells were still sensitive to MALT1 inhibition by S-Mepazine. Thus, based on the genetic background combinatorial BTK and MALT1 inhibition may improve effectiveness of therapeutic treatment and reduce the chances for the development of drug resistances. PMID- 26540569 TI - Differentiation between genetic mutations of breast cancer by breath volatolomics. AB - Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses. PMID- 26540571 TI - Social inequalities and cancer: can the European deprivation index predict patients' difficulties in health care access? a pilot study. AB - CONTEXT: The European Deprivation Index (EDI), is a new ecological estimate for Socio-Economic Status (SES). This study postulates that Time-To-Treatment could be used as a cancer quality-of -care surrogate in order to identify the association between cancer patient's SES and quality of care in a French comprehensive cancer center. METHODS: retrospective mono-centered cohort study. All consecutive incoming adult patients diagnosed for breast cancer (BC), prostate cancer (PC), colorectal cancer (CRC), lung cancer (LC) or sarcoma (S) were included between January 2013 and December 2013. The association of EDI and Time-To-Diagnosis (TTD), as well as Time-To-Treatment (TTT) was analyzed using a cox regression, and a strata analysis per tumor site was performed. RESULTS: 969 patients were included. Primitive tumor site was 505 BC (52%), 169 PC (17%), 145 LC (15%), 116 CRC (12%), and 34 S (4%). Median TTD was 1.41 months (Q1-Q3 0.5 to 3.5 months). Median TTT was 0.9 months (0.4 - 1.4). In a multivariate analysis, we identified the tumor site as a predictive factor to influence TTD, shorter for BC (0.75 months, [0.30- 1.9]) than PC (4.69 months [1.6-29.7]), HR 0.27 95%CI = [0.22-0.34], p < 0.001. TTT was also shorter for BC (0.75 months [0.4-1.1]) than PC (2.02 [0.9-3.2]), HR 0.32 95%CI = [0.27-0.39], p < 0.001. EDI quintiles were not found associated with either TTT or TTD. CONCLUSIONS: Deprivation estimated by the EDI does not appear to be related to an extension of the Time-to-Diagnosis or Time-to-Treatment in our real-life population. Further research should be done to identify other frailty-sensitive factors that could be responsible for delays in care. PMID- 26540572 TI - Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer. AB - Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy. PMID- 26540573 TI - Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. AB - A sharp definition of what a senescent cell is still lacking since we do not have in depth understanding of mechanisms that induce cellular senescence. In addition, senescent cells are heterogeneous, in that not all of them express the same genes and present the same phenotype. To further clarify the classification of senescent cells, hints may be derived by the study of cellular metabolism, autophagy and proteasome activity. In this scenario, we decided to study these biological features in senescence of Mesenchymal Stromal Cells (MSC). These cells contain a subpopulation of stem cells that are able to differentiate in mesodermal derivatives (adipocytes, chondrocytes, osteocytes). In addition, they can also contribute to the homeostatic maintenance of many organs, hence, their senescence could be very deleterious for human body functions. We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation and replicative exhaustion. The first three are considered inducers of acute senescence while extensive proliferation triggers replicative senescence also named as chronic senescence. In all conditions, but replicative and high IR dose senescence, we detected a reduction of the autophagic flux, while proteasome activity was impaired in peroxide-treated and irradiated cells. Differences were observed also in metabolic status. In general, all senescent cells evidenced metabolic inflexibility and prefer to use glucose as energy fuel. Irradiated cells with low dose of X-ray and replicative senescent cells show a residual capacity to use fatty acids and glutamine as alternative fuels, respectively. Our study may be useful to discriminate among different senescent phenotypes. PMID- 26540575 TI - Chronotypes in patients with nonseasonal depressive disorder: Distribution, stability and association with clinical variables. AB - The individual's chronotype is regarded as rather stable trait with substantial heritability and normal distribution of the "morningness-eveningness" dimension in the general population. Eveningness has been related to the risk of developing affective, particularly depressive, disorders. However, age and other sociobiological factors may influence chronotypes. The present study investigated the distribution, stability, and clinical correlates of chronotype and morningness-eveningness in hospitalized patients with affective disorder. Chronotype was assessed with the morningness-eveningness questionnaire (MEQ) in 93 patients with nonseasonal depressive syndrome (85% major depression; 15% depressive adjustment disorder) after admission, and in 19 patients again before discharge. Distribution, stability and correlations of MEQ scores with clinical variables were calculated. Additionally, a literature analysis of chronotype distributions in samples of nondepressed persons and patients with nonseasonal depression was carried out. MEQ scores (mean 49 +/- 11, range 23-75, higher scores indicate morningness) in 93 acutely depressed inpatients (age 41 +/- 14 years, range 18-75 years; 63% women; hospitalization 48 +/- 22 days; BDI-II 32 +/ 11) were normally distributed (Shapiro-Wilk test; W = 0.993, p = 0.920) with 59.1% intermediate types, 19.4% evening types, and 21.5% morning types. MEQ change scores from admission to discharge were nonsignificant (-1.3 +/- 5.0; paired t-test, t18 = -1.09; p = 0.29) despite significantly improved depression scores (-19.4 +/- 7.6; paired t-test, t18 = 11.2, p < 0.001). Age (r = 0.24), and depression scores (r = -0.21) correlated significantly (p < 0.05) with MEQ scores; associations with sex and hospitalization duration were nonsignificant. The present study and literature findings revealed that the frequency of evening types is not clearly elevated in depression, but morning types are less frequent compared to healthy samples (p < 0.001). Morningness-eveningness scores were normally distributed and stable in depressive inpatients. In line with previous findings, but contrary to theoretical assumptions, evening types were not overrepresented in depressed patients. Additionally, relatively less morning types and more intermediate types were found in depressed patients. Future studies should focus on transitions from morning to intermediate types as a tentative risk or correlate of emerging depression. PMID- 26540576 TI - Proteomic Analysis of Macular Fluid Associated With Advanced Glaucomatous Excavation. PMID- 26540577 TI - Chemical composition of the essential oil from Thapsia garganica L. (Apiaceae) grown wild in Sicily and its antimicrobial activity. AB - In this study, the chemical composition of the essential oil from flowers and leaves of Thapsia garganica L. collected in Sicily was evaluated by GC and GC-MS. The main components of T. garganica flower oil (T.f.) were chamazulene (58.3%), humulene oxide II (9.0%), tricosane (8.2%) and pentacosane (8.2%). Also the oil from leaves (T.l.) was characterised by high content of chamazulene (49.2%). Other abundant metabolites were 1,4-dimethylazulene (18.5%), (E)-phytol (6.3%) and neophytadiene (5.1%). The comparison with other studied oils of genus Thapsia is discussed. Antimicrobial activity against several micro-organisms, including some ones infesting historical art craft, was also determined. PMID- 26540574 TI - A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression. AB - In response to microenvironmental signals, macrophages undergo different types of activation, including the "classic" pro-inflammatory phenotype (also called M1) and the "alternative" anti-inflammatory phenotype (also called M2). Macrophage polarized activation has profound effects on immune and inflammatory responses, but mechanisms underlying the various types of macrophage is still in its infancy. In this study, we reported that M1-type stimulation could down-regulate miR-23a/27a/24-2 cluster transcription through the binding of NF-kappaB to this cluster's promoter and that miR-23a in turn activated the NF-kappaB pathway by targeting A20 and thus promoted the production of pro-inflammatory cytokines. Furthermore, STAT6 occupied the miR-23a/27a/24-2 cluster promoter and activated their transcription in IL-4-stimulated macrophages. In addition, miR-23a in turn suppressed the JAK1/STAT-6 pathway and reduced the production of M2 type cytokines by targeting JAK1 and STAT-6 directly, while miR-27a showed the same phenotype by targeting IRF4 and PPAR-gamma. The miR-23a/27a/24-2 cluster was shown to be significantly decreased in TAMs of breast cancer patients, and macrophages overexpressing the miR-23a/27a/24-2 cluster inhibited tumor growth in vivo. Taken together, these data integrated microRNA expression and function into macrophage polarization networks and identified a double feedback loop consisting of the miR-23a/27a/24-2 cluster and the key regulators of the M1 and M2 macrophage polarization pathway. Moreover, miR-23a/27a/24-2 regulates the polarization of tumor-associated macrophages and thus promotes cancer progression. PMID- 26540578 TI - The complete mitochondrial genome of Colobus angolensis palliatus. AB - Colobus angolensis palliatus (C.a. palliatus), known as the angolan black-and white colobus monkey, is an Old World monkey, belonging to the Colobus genus. It is a subspecies of C. angolensis. Here, we describe the complete mitochondrial genome (mitogenome) sequence of C.a. palliatus. The genome is 16 850 bp in length, comprising 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a major non coding region. Phylogenic tree was constructed based on the complete mitogenome of C.a. palliatus and closely related 13 colobinae species to estimate their phylogenic relationship. We present an important genetic resource for the black and-white colobus monkeys. PMID- 26540579 TI - Primary Amebic Meningoencephalitis Associated with Hot Spring Exposure During International Travel - Seminole County, Florida, July 2014. PMID- 26540580 TI - Neutrophil-lymphocyte ratio predicts cardiovascular and all-cause mortality in hemodialysis patients. AB - Neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been shown to predict mortality in patients with malignancies, ischemic heart disease and peripheral vascular disease. Its prognostic value in hemodialysis patients is unclear. The aims of this study were to: (i) explore the relationship between NLR and other biochemical parameters and (ii) to examine the value of NLR as a predictor of cardiovascular and all-cause mortality in hemodialysis patients. The study included all the incident hemodialysis patients from a single center between 2007 and 2012. NLR was calculated using samples obtained 3 months after commencing hemodialysis. One hundred seventy hemodialysis patients were included with a median follow-up of 37 months. There were 54 deaths (32%). NLR was positively correlated with C-reactive protein (r = 0.24, p = 0.0023) and negatively correlated with hemoglobin (r = -0.27, p = 0.00048), albumin (r = 0.23, p = 0.0034) and total cholesterol (r = -0.17, p = 0.049) levels. In multivariate Cox regression, NLR was independently associated with both all-cause mortality (adjusted hazard ratio [HR] 1.4; 95% confidence interval [CI], 1.2-1.6; p <= 0.0001) and cardiovascular death (HR 1.3, 95% CI 1.1-1.6, p = 0.0032). Other predictors of all-cause mortality were age (HR 1.6 per decade; 95% CI, 1.2-2.1; p = 0.0017), body mass index (HR 0.93; 95% CI, 0.88-0.98; p = 0.0047), albumin (HR 0.91; 95% CI, 0.86-0.97; p = 0.0035) and peripheral vascular disease (HR 2.7; 95% CI, 1.4-5.1; p = 0.0023). NLR is a practical, cost-efficient and easy to use predictor of cardiovascular and all-cause mortality in incident hemodialysis patients. PMID- 26540581 TI - Movies and Water-How Does Telehealth Fit? PMID- 26540582 TI - Pursuit of Value in Connected Healthcare. AB - INTRODUCTION: Potential for direct patient care through remote exchange of health related information has expanded enormously with the proliferation of technologies leveraging ubiquitous connectivity, but implementation of connected care has been slow and controversial. MATERIALS AND METHODS: This review demonstrates that controversy regarding connected care arises largely from the fact that proponents and critics are generally considering distinctly different care models. Differences are highlighted to mitigate controversy and to distinguish capacities of these different models. RESULTS: Distinguishing capacities is essential for establishing the evidence base supporting safety, effectiveness, and efficiency. In care of a particular patient's problem, value is achieved when resources allocated meet requirements for diagnosis and intervention but do not exceed them. Robust evidence supports the value of some well-defined connected care models, exemplified by the Health-e-Access Telemedicine Model. CONCLUSIONS: The pursuit of value in connected care is fundamentally the same as with in-person care. Provider organizations, legislators, regulators, and payers face not only a complex task in defining standards and enabling appropriate use, but also a heavy burden of responsibility for unleashing connected care that will benefit the entire community. PMID- 26540583 TI - Complete mitochondrial genome of the yellowbelly threadfin bream, Nemipterus bathybius (Perciformes, Nemipteridae). AB - The complete mitogenome of the yellowbelly threadfin bream, Nemipterus bathybius, has been reported for the first time in this study. The circular mtDNA molecule was 17 353 bp in size and the overall nucleotide composition of H-strand was 29.0% A, 28.3% T, 16.5% G, and 26.2% C, with an A + T bias. The complete mitogenome encoded 13 protein-coding genes, 2 rRNAs, 22 tRNAs, and 2 non-coding regions, as found in other typical vertebrate mitogenomes. The D-loop located between tRNAPro and tRNAPhe genes and the length was 1603 bp, rich in A + T (73.0%). The phylogenetic tree of complete mitogenome sequences of 12 families and 26 species showed that the family Nemipteridae was in the basal position of the suborder Percoidei, whereas its two associated families (Sparidae and Lethrinidae) were clustered together with other 7 families, which supported a non monophyly of superfamily Sparoidea. PMID- 26540584 TI - Telemental health for children and adolescents. AB - Most children and adolescents across the USA fail to receive adequate mental health services, especially in rural or underserved communities. The supply of child and adolescent psychiatrists is insufficient for the number of children in need of services and is not anticipated to grow. This calls for novel approaches to mental health care. Telemental health (TMH) offers one approach to increase access. TMH programmes serving young people are developing rapidly and available studies demonstrate that these services are feasible, acceptable, sustainable and likely as effective as in-person services. TMH services are utilized in clinical settings to provide direct care and consultation to primary care providers (PCPs), as well as in non-traditional settings, such as schools, correctional facilities and the home. Delivery of services to young people through TMH requires several adjustments to practice with adults regarding the model of care, cultural values, participating adults, rapport-building, pharmacotherapy and psychotherapy. Additional infrastructure accommodations at the patient site include space and staffing to conduct developmentally appropriate evaluations and treatment planning with parents, other providers, and community services. For TMH to optimally impact young people's access to mental health care, collaborative models of care are needed to support PCPs as frontline mental health-care providers, thereby effectively expanding the child and adolescent mental health workforce. PMID- 26540585 TI - Mycobacterium avium complex disseminated infection in a kidney transplant recipient. AB - Mycobacterium avium-intracellulare complex (MAC) infections are well known in immunocompromised patients, notably in human immunodeficiency virus infection, but remain scarcely described in kidney transplantation. Moreover, cutaneous involvement in this infection is very unusual. We describe here a disseminated infection caused by MAC in a kidney transplant recipient revealed by cutaneous lesions. This case highlights the need for an exhaustive, iterative microbiologic workup in the context of an atypical disease presentation in a renal transplant patient, regardless of the degree of immunosuppression. PMID- 26540586 TI - The complete mitochondrial DNA genome of a Chloridea (Heliothis) subflexa (Lepidoptera: Noctuidae) morpho-species. AB - We investigate the complete mitogenome of a pheromone-trapped morpho-species of Chloridea subflexa from Brazil (initially identified by the Sanger sequencing of partial mtCOI gene) as 15 323 bp (KT598688) via next generation sequencing platform. The mitogenome has an A/T rich base composition (A: 40.4%; T: 40.3%; C: 11.5%; G: 7.8%), and included 13 protein-coding genes (PCGs), 22 tRNAs, 2 ribosomal RNAs and a putative replication region (ca. 323 bp). All PCGs start with a methionine (M) amino acid except the COI gene which has an arginine (R). The trnL2 and trn-Lys genes were partially embedded within the COII gene, while the trn-His gene was completely embedded within the ND4 gene. All PCGs ends with the "TAA" stop codon except ND3 which has a "TAG" stop codon. PMID- 26540588 TI - Imaging fluorescence (cross-) correlation spectroscopy in live cells and organisms. AB - Single-plane illumination (SPIM) or total internal reflection fluorescence (TIRF) microscopes can be combined with fast and single-molecule-sensitive cameras to allow spatially resolved fluorescence (cross-) correlation spectroscopy (FCS or FCCS, hereafter referred to FCS/FCCS). This creates a powerful quantitative bioimaging tool that can generate spatially resolved mobility and interaction maps with hundreds to thousands of pixels per sample. These massively parallel imaging schemes also cause less photodamage than conventional single-point confocal microscopy-based FCS/FCCS. Here we provide guidelines for imaging FCS/FCCS measurements on commercial and custom-built microscopes (including sample preparation, setup calibration, data acquisition and evaluation), as well as anticipated results for a variety of in vitro and in vivo samples. For a skilled user of an available SPIM or TIRF setup, sample preparation, microscope alignment, data acquisition and data fitting, as described in this protocol, will take ~1 d, depending on the sample and the mode of imaging. PMID- 26540589 TI - Direct conversion of human amniotic cells into endothelial cells without transitioning through a pluripotent state. AB - Endothelial cells (ECs) have essential roles in organ development and regeneration, and therefore they could be used for regenerative therapies. However, generation of abundant functional endothelium from pluripotent stem cells has been difficult because ECs generated by many existing strategies have limited proliferative potential and display vascular instability. The latter difficulty is of particular importance because cells that lose their identity over time could be unsuitable for therapeutic use. Here, we describe a 3-week platform for directly converting human mid-gestation lineage-committed amniotic fluid-derived cells (ACs) into a stable and expandable population of vascular ECs (rAC-VECs) without using pluripotency factors. By transient expression of the ETS transcription factor ETV2 for 2 weeks and constitutive expression the ETS transcription factors FLI1 and ERG1, concomitant with TGF-beta inhibition for 3 weeks, epithelial and mesenchymal ACs are converted, with high efficiency, into functional rAC-VECs. These rAC-VECs maintain their vascular repertoire and morphology over numerous passages in vitro, and they form functional vessels when implanted in vivo. rAC-VECs can be detected in recipient mice months after implantation. Thus, rAC-VECs can be used to establish a cellular platform to uncover the molecular determinants of vascular development and heterogeneity and potentially represent ideal ECs for the treatment of regenerative disorders. PMID- 26540591 TI - Laterally Ordered Sub-10 nm Features Obtained From Directed Self-Assembly of Si Containing Block Copolymer Thin Films. AB - Laterally ordered sub-10 nm features are produced from the directed self-assembly of poly(1,1-dimethyl silacyclo-butane)-block-poly(methyl methacrylate) (PDMSB-b PMMA) thin films on sinusoidal azobenzene-containing patterns. The use of sinusoidal surface relief grating enables the formation of very large grain areas (over several um(2) ) consisting of out-of-plane PMMA cylinders. PMID- 26540590 TI - Single-cell Hi-C for genome-wide detection of chromatin interactions that occur simultaneously in a single cell. AB - Hi-C is a powerful method that provides pairwise information on genomic regions in spatial proximity in the nucleus. Hi-C requires millions of cells as input and, as genome organization varies from cell to cell, a limitation of Hi-C is that it only provides a population average of genome conformations. We developed single-cell Hi-C to create snapshots of thousands of chromatin interactions that occur simultaneously in a single cell. To adapt Hi-C to single-cell analysis, we modified the protocol to include in-nucleus ligation. This enables the isolation of single nuclei carrying Hi-C-ligated DNA into separate tubes, followed by reversal of cross-links, capture of biotinylated ligation junctions on streptavidin-coated magnetic beads and PCR amplification of single-cell Hi-C libraries. The entire laboratory protocol can be carried out in 1 week, and although we have demonstrated its use in mouse T helper (TH1) cells, it should be applicable to any cell type or species for which standard Hi-C has been successful. We also developed an analysis pipeline to filter noise and assess the quality of data sets in a few hours. Although the interactome maps produced by single-cell Hi-C are sparse, the data provide useful information to understand cellular variability in nuclear genome organization and chromosome structure. Standard wet and dry laboratory skills in molecular biology and computational analysis are required. PMID- 26540592 TI - Oral Cancer Chemoprevention--The End of EPOC, the Beginning of an Epoch of Molecular Selection. PMID- 26540593 TI - Confirmation of etiology in fetal hydrops by sonographic evaluation of fluid allocation patterns. AB - OBJECTIVE: To evaluate patterns of fluid allocations in different etiologies of hydrops fetalis. STUDY DESIGN: This report is a retrospective cohort study on 20,395 fetal sonographic evaluations in a single tertiary center from 2000 to 2014. Special emphasis was placed on the exact description of the distinct fluid allocation sites in each fetus. Postmortem/postnatal records were evaluated additionally. Mean follow up of the surviving neonates was 34 days (10-60 days). RESULTS: There seem to be distinctive patterns of fluid allocation in some etiologies leading to fetal hydrops including aneuploidies and Parvovirus B19 related infections. CONCLUSION: Due to the allocation patterns of fluid filled sites in fetuses with hydrops fetalis the spectrum of possible etiologies may be narrowed already during initial ultrasound scan. It can contribute substantially to diagnostic accuracy as well as to parental counseling. This knowledge may also help to omit delay in diagnostic routines. PMID- 26540594 TI - Comparison of bidirectional barbed suture Stratafix and conventional suture with intracorporeal knots in laparoscopic myomectomy by office transvaginal hydrolaparoscopic follow-up: a preliminary report. AB - OBJECTIVES: To compare surgical outcomes of different types of intracorporeal sutures for laparoscopic posterior myomectomy, by a prospective randomized study. STUDY DESIGN: Prospective randomized study on 47 patients with single posterior intramural myoma (4-7cm in diameter) undergoing laparoscopic myomectomy. The patients enrolled were divided into two groups, one operated using conventional suture in double strand, and the other with bidirectional barbed suture Stratafix. The main outcome measures were suturing time, peri-operative variables, and post-operative adhesions in both groups. RESULTS: The mean operative time was shorter with the StratafixTM than with the conventional suture (66.3+/-8.2 vs. 73+/-8min; p=0.005). Suturing time was significantly shorter in the StratafixTM than in the control group (8.8+/-2.4 vs. 15.5+/-2.8min; p=0.001). Intraoperative bleeding was significantly less in the Stratafix group (p=0.0012). Conversely, there was no statistically significant difference for postoperative adhesions between the two groups (26.7% vs. 21.4% p=0.5). CONCLUSIONS: The use of barbed suture may reduce operative time, suturing time, and blood loss. No difference in post operative adhesions was found. PMID- 26540595 TI - Constitutive Triglyceride Turnover into the Mesenteric Lymph Is Unable to Support Efficient Lymphatic Transport of a Biomimetic Triglyceride Prodrug. AB - The triglyceride (TG) mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) biochemically integrates into intestinal lipid transport and lipoprotein assembly pathways and thereby promotes the delivery of mycophenolic acid (MPA) into the lymphatic system. As lipoprotein (LP) formation occurs constitutively, even in the fasted state, the current study aimed to determine whether lymphatic transport of 2-MPA-TG was dependent on coadministered exogenous lipid. In vitro incubation of the prodrug with rat digestive fluid and in situ intestinal perfusion experiments revealed that hydrolysis and absorption of the prodrug were relatively unaffected by the quantity of lipid in formulations. In vivo studies in rats, however, showed that the lymphatic transport of TG and 2 MPA-TG was significantly higher following administration with higher quantities of lipid and that oleic acid (C18:1) was more effective in promoting prodrug transport than lipids with higher degrees of unsaturation. The recovery of 2-MPA TG and TG in lymph correlated strongly (R(2) = 0.99) and more than 97% of the prodrug was associated with chylomicrons. Inhibition of LP assembly by Pluronic L81 simultaneously inhibited the lymphatic transport of 2-MPA-TG and TG. In conclusion, although the TG mimetic prodrug effectively incorporates into TG resynthetic pathways, lipid coadministration is still required to support efficient lymphatic transport. PMID- 26540596 TI - Cyclic Cationic Peptides Containing Sugar Amino Acids Selectively Distinguishes and Inhibits Maturation of Pre-miRNAs of the Same Family. AB - The discovery of microRNAs (miRNAs) has added a new dimension to the gene regulatory networks, making aberrantly expressed miRNAs as therapeutically important targets. Small molecules that can selectively target and modulate miRNA levels can thus serve as lead structures. Cationic cyclic peptides containing sugar amino acids represent a new class of small molecules that can target miRNA selectively. Upon treatment of these small molecules in breast cancer cell line, we profiled 96 therapeutically important miRNAs associated with cancer and observed that these peptides can selectively target paralogous miRNAs of the same seed family. This selective inhibition is of prime significance in cases when miRNAs of the same family have tissue-specific expression and perform different functions. During these conditions, targeting an entire miRNA family could lead to undesired adverse effects. The selective targeting is attributable to the difference in the three-dimensional structures of precursor miRNAs. Hence, the core structure of these peptides can be used as a scaffold for designing more potent inhibitors of miRNA maturation and hence function. PMID- 26540597 TI - Characteristics and Risk Factors of Spinal Fractures in Recreational Snowboarders Attending an Emergency Department in Japan. AB - OBJECTIVE: The purpose of this study was to elucidate the characteristics of spinal fractures during recreational snowboarding and to determine the risk factors for these fractures. DESIGN: Case series study. SETTING: The Oku-mino ski area during the 7-year period between the 2005 to 2006 and 2011 to 2012 skiing seasons. PARTICIPANTS: Eight thousand seven hundred twenty-three snowboarders with injures. INTERVENTIONS: Cases involved snowboarders with spinal fractures; controls were snowboarders without spinal fractures. MAIN OUTCOME MEASURES: The characteristics of spinal fractures were assessed using a standard form and patient records, including radiographs. Multivariate regression analysis was performed to investigate risk factors for spinal fractures, including age, type of slope, snow condition, accident cause, self-reported skill level, experience level, and the use of protective equipment. RESULTS: Of 8723 snowboarders with injuries, 431 snowboarders presented with spinal fractures (4.9%). The most common spinal fracture was isolated transverse process fracture in the lumbar spine (33.2%, n = 143), followed by compression type fracture in the lumbar spine (25.1%, n = 108). Age (20-39 years), terrain slopes (half-pipe/box/kicker/rail), and jump-landing failure were associated with a significantly high risk of spinal fracture. CONCLUSIONS: Among the recreational snowboarders, isolated transverse process fracture in the lumbar spine was the most frequent spinal fracture. Age (20-39 year old), terrain slopes, and jump-landing failure were found to be risk factors for spinal fracture. CLINICAL RELEVANCE: Identification of characteristics and risk factors for spinal fractures during snowboarding is useful information to create a preventive strategy for the fractures and make snowboarding a safer sport. PMID- 26540598 TI - Content, Delivery, and Effectiveness of Concussion Education for US College Coaches. AB - OBJECTIVE: The primary objective of this study was to examine the proportion of US college coaches who receive annual concussion education from their institution and to describe the content and delivery modalities of this education. This study also tested the hypothesis that coaches receiving concussion education from their institution will have greater knowledge about concussions independent of other individual and institutional characteristics. DESIGN: Cross-sectional online survey. SETTING: US college sport. PARTICIPANTS: College coaches in National Collegiate Athletic Association Division I, II, and III (n = 1818). INDEPENDENT VARIABLES: Self-reported receipt of education from institution, sex, sport coached, division of competition. MAIN OUTCOME MEASURES: Concussion identification and management knowledge. RESULTS: Two-thirds of coaches reported receiving informational materials about concussion from their institution. The content of the education most frequently referred to symptoms of a concussion and information about proper management of a concussion. Coaches who received educational materials from their institution were better able to identify symptoms and had more conservative responses to concussion management scenarios. Male coaches of male contact or collision teams less frequently endorsed safe or correct response as compared with female coaches of noncontact or collision teams. CONCLUSIONS: Not all US college coaches receive concussion education from their institution. Male Division I coaches of male contact/collision sport are a population for whom targeted educational outreach may be particularly valuable. CLINICAL RELEVANCE: Education for coaches, delivered by clinicians at many institutions, is an important component of ensuring that coaches are prepared to be informed partners in supporting concussion safety. PMID- 26540599 TI - Prophylactic Valacyclovir to Prevent Outbreaks of Primary Herpes Gladiatorum at a 28-Day Wrestling Camp: A 10-Year Review. AB - OBJECTIVE: To determine efficacy of using oral antiviral medication to reduce herpes gladiatorum (HG) at summer high-school wrestling camps. DESIGN: Usage of antiviral medication hypothetically reduces the likelihood of HG outbreaks. This is an observational study examining the effectiveness of oral antiviral medications in reducing outbreaks of HG because of Herpes Simplex type-1 virus (HSV). SETTING: A 28-day high-school summer wrestling camp at the University of Minnesota from 2003 to 2012. PARTICIPANTS: Each summer approximately 300 high school wrestlers, age 13 to 18 years of age, participated in this camp. INTERVENTIONS: All athletes were recommended to take valacyclovir 1 g once a day for the duration of the camp. Athletes who did not use any antiviral medication comprised the comparison group for this study. Individuals were screened daily and those with outbreaks of HG were withheld from practice for 120 hours in accordance with National Collegiate Athletic Association/National Federation of State High School Associations guidelines. MAIN OUTCOME MEASURES: To measure viral outbreaks of HG due to HSV-1, determine level of compliance, and determine efficacy of antiviral medication in reducing the occurrence of HG at this 28-day wrestling camp. RESULTS: Of the 2793 athletes who completed camp, 1995 (71%) used antiviral medication, and 36 outbreaks occurred. Eighty-four athletes had a known history of HG/recurrent herpes labialis. Overall, prophylactic antiviral medication resulted in an 84.7% decrease in the probability of an outbreak. Prophylactic valacyclovir (1 g daily) lowered the incidence of individual outbreaks by 89.5%. CONCLUSIONS: Prophylactic use of valacyclovir 1 g once a day is efficacious in lowering the incidence of HSV outbreaks among adolescents at a 28-day wrestling camp. PMID- 26540600 TI - No Effect of Acupuncture in the Relief of Delayed-Onset Muscle Soreness: Results of a Randomized Controlled Trial. AB - BACKGROUND: Delayed-onset muscle soreness (DOMS) is a common symptom in people participating in exercise, sport, or recreational physical activities. Several remedies have been proposed to prevent and alleviate DOMS. DESIGN AND METHODS: A five-arm randomized controlled study was conducted to examine the effects of acupuncture on eccentric exercise-induced DOMS of the biceps brachii muscle. Participants were recruited through convenience sampling of students and general public. Participants were randomly allocated to needle, laser, sham needle, sham laser acupuncture, and no intervention. Outcome measures included pressure pain threshold (PPT), pain intensity (visual analog scale), and maximum isometric voluntary force. RESULTS: Delayed-onset muscle soreness was induced in 60 participants (22 females, age 23.6 +/- 2.8 years, weight 66.1 +/- 9.6 kg, and height 171.6 +/- 7.9 cm). Neither verum nor sham interventions significantly improved outcomes within 72 hours when compared with no treatment control (P > 0.05). CONCLUSIONS: Acupuncture was not effective in the treatment of DOMS. From a mechanistic point of view, these results have implications for further studies: (1) considering the high-threshold mechanosensitive nociceptors of the muscle, the cutoff for PPT (5 kg/cm) chosen to avoid bruising might have led to ceiling effects; (2) the traditional acupuncture regimen, targeting muscle pain, might have been inappropriate as the DOMS mechanisms seem limited to the muscular unit and its innervation. Therefore, a regionally based regimen including an intensified intramuscular needling (dry needling) should be tested in future studies, using a higher cutoff for PPT to avoid ceiling effects. PMID- 26540601 TI - Young Athletes' Concerns About Sport-Related Concussion: The Patient's Perspective. AB - OBJECTIVE: Few studies have examined the experience and concerns of the concussed athlete. The purpose of this study was to identify the most pressing concerns of athletes with concussion. DESIGN: Cross-sectional survey of athletes who presented for evaluation of a new sport-related concussion during an 8-month period. SETTING: Tertiary-level sports medicine division of a large academic pediatric medical center. PARTICIPANTS: One hundred twenty one patients (67 male, 54 female) aged 8 to 18 years who had sustained a sport-related concussion participated in the study by responding to "What is the worst thing for you about having a concussion?" on the study questionnaire. Questionnaires were completed in the clinic waiting room before the visit with a provider. INTERVENTION: Inductive content analysis was used to identify themes in the responses to the study question. MAIN OUTCOME MEASURES: Age, sex, sport played at the time of the current injury, history of previous concussion, known contacts with concussion, and subjective report of worst aspect of concussion. RESULTS: Seventy respondents (57.9%) cited symptoms, and 68 (56.2%) reported loss of activity as the worst part of concussion, including 17 (14.0%) who listed both symptoms and loss of activity. CONCLUSIONS: Over half of concussed athletes indicate that the most distressing part of the injury is loss of activities, which may result from symptoms of the injury itself and/or the prescribed treatment. CLINICAL RELEVANCE: Health care providers should not underestimate the degree to which symptoms and loss of activities affect young athletes' general well-being. In addition to the negative impact of concussion symptoms, there is an obvious cost of physical, cognitive, and social activity restrictions for patients recovering from sport-related concussions that should be explicitly addressed. PMID- 26540602 TI - Greenhouse gases emission from soils under major crops in Northwest India. AB - Quantification of greenhouse gases (GHGs) emissions from agriculture is necessary to prepare the national inventories and to develop the mitigation strategies. Field experiments were conducted during 2008-2010 at the experimental farm of the Indian Agricultural Research Institute, New Delhi, India to quantify nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) emissions from soils under cereals, pulses, millets, and oilseed crops. Total cumulative N2O emissions were significantly different (P>0.05) among the crop types. Emission of N2O as percentage of applied N was the highest in pulses (0.67%) followed by oilseeds (0.55%), millets (0.43%) and cereals (0.40%). The emission increased with increasing rate of N application (r(2)=0.74, P<0.05). The cumulative flux of CH4 from the rice crop was 28.64+/-4.40 kg ha(-1), while the mean seasonal integrated flux of CO2 from soils ranged from 3058+/-236 to 3616+/-157 kg CO2 ha(-1) under different crops. The global warming potential (GWP) of crops varied between 3053 kg CO2 eq. ha(-1) (pigeon pea) and 3968 kg CO2 eq. ha(-1) (wheat). The carbon equivalent emission (CEE) was least in pigeon pea (833 kg C ha(-1)) and largest in wheat (1042 kg C ha(-1)). The GWP per unit of economic yield was the highest in pulses and the lowest in cereal crops. The uncertainties in emission values varied from 4.6 to 22.0%. These emission values will be useful in updating the GHGs emission inventory of Indian agriculture. PMID- 26540603 TI - Airport take-off noise assessment aimed at identify responsible aircraft classes. AB - Assessment of aircraft noise is an important task of nowadays airports in order to fight environmental noise pollution given the recent discoveries on the exposure negative effects on human health. Noise monitoring and estimation around airports mostly use aircraft noise signals only for computing statistical indicators and depends on additional data sources so as to determine required inputs such as the aircraft class responsible for noise pollution. In this sense, the noise monitoring and estimation systems have been tried to improve by creating methods for obtaining more information from aircraft noise signals, especially real-time aircraft class recognition. Consequently, this paper proposes a multilayer neural-fuzzy model for aircraft class recognition based on take-off noise signal segmentation. It uses a fuzzy inference system to build a final response for each class p based on the aggregation of K parallel neural networks outputs Op(k) with respect to Linear Predictive Coding (LPC) features extracted from K adjacent signal segments. Based on extensive experiments over two databases with real-time take-off noise measurements, the proposed model performs better than other methods in literature, particularly when aircraft classes are strongly correlated to each other. A new strictly cross-checked database is introduced including more complex classes and real-time take-off noise measurements from modern aircrafts. The new model is at least 5% more accurate with respect to previous database and successfully classifies 87% of measurements in the new database. PMID- 26540604 TI - A review of the work of the EU Reference Laboratory supporting the authorisation process of feed additives in the EU. [corrected]. AB - This paper describes the operation of the European Union Reference Laboratory for Feed Additives (EURL) and its role in the authorisation procedure of feed additives in the European Union. Feed additives are authorised according to Regulation (EC) No. 1831/2003, which introduced a completely revised authorisation procedure and also established the EURL. The regulations authorising feed additives contain conditions of use such as legal limits of the feed additives, which require the availability of a suitable method of analysis for official control purposes under real world conditions. It is the task of the EURL to evaluate the suitability of analytical methods as proposed by the industry for this purpose. Moreover, the paper shows that one of the major challenges is the huge variety of the methodology applied in feed additive analysis, thus requiring expertise in quite different analytical areas. In order to cope with this challenge, the EURL is supported by a network of national reference laboratories (NRLs) and only the merged knowledge of all NRLs allows for a scientifically sound assessment of the analytical methods. PMID- 26540605 TI - Excess body weight increases the burden of age-associated chronic diseases and their associated health care expenditures. AB - Aging and excessive adiposity are both associated with an increased risk of developing multiple chronic diseases, which drive ever increasing health costs. The main aim of this study was to determine the net (non-estimated) health costs of excessive adiposity and associated age-related chronic diseases. We used a prevalence-based approach that combines accurate data from the Health Search CSD LPD, an observational dataset with patient records collected by Italian general practitioners and up-to-date health care expenditures data from the SiSSI Project. In this very large study, 557,145 men and women older than 18 years were observed at different points in time between 2004 and 2010. The proportion of younger and older adults reporting no chronic disease decreased with increasing BMI. After adjustment for age, sex, geographic residence, and GPs heterogeneity, a strong J-shaped association was found between BMI and total health care costs, more pronounced in middle-aged and older adults. Relative to normal weight, in the 45-64 age group, the per-capita total cost was 10% higher in overweight individuals, and 27 to 68% greater in patients with obesity and very severe obesity, respectively. The association between BMI and diabetes, hypertension and cardiovascular disease largely explained these elevated costs. PMID- 26540606 TI - Water-soluble ferulic acid derivatives improve amyloid-beta-induced neuronal cell death and dysmnesia through inhibition of amyloid-beta aggregation. AB - Ferulic acid (FA) has been reported to exhibit protective effects against amyloid beta (Abeta)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water soluble FA derivatives on Abeta-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Abeta aggregation and destabilized pre-aggregated Abeta to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Abeta-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water soluble FA derivatives to mice improved Abeta-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Abeta induced neurotoxicity. This study provides useful evidence suggesting that water soluble FA derivatives are expected to be effective neuroprotective agents. PMID- 26540607 TI - Survival rate and prognostic factors of conventional osteosarcoma in Northern Thailand: A series from Chiang Mai University Hospital. AB - BACKGROUND: Osteosarcoma is a common and aggressive primary malignant bone tumor occurring in children and adolescents. It is one of the most aggressive human cancers and the most common cause of cancer-associated limb loss. As treatment in Thailand has produced a lower survival rate than in developed countries; therefore, this study identified survival rate and the poor prognostic factors of osteosarcoma in Northern Thailand. METHODS: The retrospective cases of osteosarcoma, diagnosis between 1 January 1996 and 31 December 2013, were evaluated. Five and ten year overall survival rates were analyzed using time-to event analysis. Potential prognostic factors were identified by multivariate regression analysis. RESULTS: There were 208 newly diagnosed osteosarcomas during that period, and 144 cases met the criteria for analysis. The majority of the osteosarcoma cases (78.5%) were aged 0-24 years. The overall 5- and 10-year survival rates were 37.9% and 33.6%, respectively. Presence of metastasis at initial examination, delayed and against treatment co-operation, and axial skeletal location were identified as independent prognostic factors for survival, with hazard ratios of 4.3, 2.5 and 3.8, and 3.1, respectively. CONCLUSIONS: This osteosarcoma cohort had a relatively poor overall survival rate. The prognostic factors identified would play a critical role in modifying survival rates of osteosarcoma patients; as rapid disease recognition, a better treatment counselling, as well as improving of chemotherapeutic regimens were found to be important in improving the overall survival rate in Thailand. PMID- 26540608 TI - Glassy Behavior of a Tin Dioxide Nanoparticle Suspension. AB - Dilute suspensions of charged colloidal particles with a short-range attraction and long-range repulsion can exhibit a variety of arrested states. In many applications using suspensions of charged nanoparticles, the optimization of the process requires the understanding of the mechanism underlying the stability and the rheological properties of the suspensions. In an attempt to clarify the solidification mechanism for dilute suspensions of tin dioxide (SnO2) nanoparticles, we present dynamic viscoelasticity, dynamic and static light scattering, and small-angle X-ray scattering experiments on a SnO2 nanoparticle suspension with a nanoparticle concentration of 25.0 wt % (volume fraction phi = 0.045). The behaviors of the observed dynamic and static structure factors reveal that the aging of SnO2 nanoparticles is Wigner glassy rather than gel-like. PMID- 26540609 TI - Molecular and Clinical Investigation of Cystinuria in the Greek-Cypriot Population. AB - BACKGROUND AND AIMS: Cystinuria represents 3% of nephrolithiasis in humans. Two genes have been identified as the main genetic causes of cystinuria, SLC3A1 and SLC7A9, with an autosomal recessive mode of inheritance. In the present study, we studied for the first time, genetically and clinically, all the cystinuric families identified so far in the Greek-Cypriot population. METHODS: Discovery of mutations was performed through polymerase chain reaction (PCR)-single analysis and DNA resequencing. New families were investigated through PCR-RFLPs. Clinical data were collected through the hospital patients' records and analytical follow up of the families. RESULTS AND DISCUSSION: We found a total of five mutations in 28 Greek-Cypriot cystinuric patients belonging in 12 families. The most frequent mutation among the 28 Greek-Cypriot patients is the SLC3A1-p.T216M, which is also the second most frequent mutation in Europe, representing a genetic founder effect. Sixteen of the 28 patients are homozygous for this mutation. Even though a consanguinity loop was obvious in only one family, other patients were from families in small villages where endogamy was practiced for many centuries. Timely clinical and genetic diagnosis, accompanied by early treatment, is significant for the good health of most of our patients. Only ~14% of them developed chronic renal failure, and only one reached end-stage renal disease (ESRD). CONCLUSION: Five SLC3A1 and SLC7A9 mutations appear to be responsible for the genetic basis of cystinuria in the Greek-Cypriot patients; having such a limited number of causative mutations will simplify diagnostics for this population. PMID- 26540610 TI - 2015 Eberhard F. Mammen Award announcements: part II-Young Investigator Awards. PMID- 26540611 TI - Current issues in hemophilia: recognizing clinical heterogeneity, replacement therapy, and outcome assessment. PMID- 26540612 TI - Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers. AB - BACKGROUND: Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that SDB and nocturnal hypoxemia are more pronounced in patients with CMS compared with healthy high-altitude dwellers, and are related to vascular dysfunction. METHODS: We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean +/- SD age, 52.8 +/- 9.8 y) and 12 healthy control subjects (47.8 +/- 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography. RESULTS: The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P < .01) than in control subjects (apnea-hypopnea index [AHI], 38.9 +/- 25.5 vs 14.3 +/- 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% +/- 3.6% vs 86.8% +/- 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 +/- 24.7 vs 14.8 +/- 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia. CONCLUSIONS: SDB and nocturnal hypoxemia are more severe in patients with CMS than in control subjects and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of the PFO may improve SDB, hypoxemia, and vascular dysfunction in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov. PMID- 26540613 TI - Retinal Toxicity of Intravitreal Polyethylene Glycol 400. AB - PURPOSE: Polyethylene glycol (PEG)-400 is a clear, colorless viscous liquid that readily dissolves many hydrophobic drugs. It is a widely used commercial solvent and vehicle for many pharmaceutical and cosmetic products. The purpose of this study is to investigate the intravitreal safety of PEG-400 to determine its suitability as a potential vehicle for intraocular drug delivery. METHODS: Six healthy, male, Dutch Belted rabbits, weighing between 2.0 and 3.0 kg, were used for this experiment. The left eye of each animal received a single 0.1 mL intravitreal injection of PEG-400. Complete eye exams and dark- and light-adapted electroretinograms (ERG) were obtained at baseline and at 1 and 4 weeks after injection. After the 4-week ERG was completed, animals were euthanized, eyes were enucleated, and histology and transmission electron microscopy (TEM) were performed. RESULTS: Ophthalmic examinations demonstrated diffuse signs of retinal degeneration and cataract formation in all 6 eyes injected with PEG-400, which was apparent at 1 week, but more evident by 4 weeks. Photopic and scotopic ERG studies demonstrated significant reduction in amplitudes at 1 and 4 weeks after injection compared to baseline. Histopathological and TEM analysis of eyes demonstrated both inner and outer retinal atrophy. CONCLUSION: Intravitreal injection of PEG-400 resulted in severe ocular toxicity. PMID- 26540614 TI - Correction: Body Fat Patterning, Hepatic Fat and Pancreatic Volume of Non-Obese Asian Indians with Type 2 Diabetes in North India: A Case-Control Study. PMID- 26540616 TI - Optimization of a Cemented Femoral Prosthesis Considering Bone Remodeling. AB - The study presents a numerical methodology for minimizing the bone loss in human femur submitted to total hip replacement (THR) procedure with focus on cemented femoral stem. Three-dimensional computational models were used to describe the femoral bone behavior. An optimization procedure using the genetic algorithm (GA) method was applied in order to minimize the bone loss, considering the geometry and the material of the prosthesis as well as the design of the stem. Internal and external bone remodeling were analyzed numerically. The numerical method proposed here showed that the bone mass loss could be reduced by 24%, changing the design parameters. PMID- 26540615 TI - Propagation of Neuronal Damage to Embryonic Grafts Transplanted in the Hippocampus of Murine Models of Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most common form of dementia, characterized by the presence of two principal hallmarks-amyloid plaques and neurofibrillary tangles. The primary cause of the majority of AD cases is not known. Likewise, the mechanisms underlying the propagation of the pathology from affected tissue to neighboring healthy neurons are largely unknown, but knowledge about them could be helpful to design strategies aimed at halting the progression of the disease. To throw light on the mechanisms of propagation of neuronal damage to healthy tissue, wild-type (WT) hippocampal solid tissue chunks derived from green fluorescent protein (GFP)-positive embryos were grafted into the hippocampus of 6 month-old WT and 3xTg-AD mice, a triple-transgenic mouse model that exhibits both amyloid-beta (Abeta) and tau protein pathology. The histological and morphological alterations of the grafted tissues were assessed 3 months post transplantation. Tissues grafted in 3xTg-AD hosts, compared to those grafted in WT recipients, presented a significant decrease in neurite outgrowth (35.4%) and dendritic spine density (41.3%), mainly due to a reduction of stubby and thin shaped spines. Moreover, some cells of the tissue transplanted in 3xTg-AD hosts accumulated intracellular amyloid peptide deposits similar to the cells of the host. Furthermore, the immunohistochemical examination of reactive astrocytes and microglia revealed the presence of more inflammation in the grafted tissues hosted in 3xTg-AD compared to WT recipients. These results show a propagation of neuronal damage to initially healthy embryonic grafts, validating this methodology for future studies on the mechanisms of the progression of AD pathology to surrounding regions. PMID- 26540617 TI - Quinone-Modified Mn-Doped ZnS Quantum Dots for Room-Temperature Phosphorescence Sensing of Human Cancer Cells That Overexpress NQO1. AB - Early detection of cancer cells in a rapid and sensitive approach is one of the great challenges in modern clinical cancer care. This study has demonstrated the first example of a rapid, selective, and sensitive phosphorescence probe based on phosphorescence energy transfer (PET) for cancer-associated human NAD(P)H: quinone oxidoreductase isozyme 1 (NQO1). An efficient room-temperature phosphorescence NQO1 probe was constructed by using Mn-doped ZnS quantum dots (Mn:ZnS QDs) as donors and trimethylquinone propionic acids as acceptors. Phosphorescence quenching of Mn:ZnS QDs from the Mn:ZnS QDs to a covalently bonded quinone was achieved through PET. Phosphorescence of Mn:ZnS QDs was turned on by the rapid reduction-initiated removal of the quinone quencher by NQO1. This probe shows low cellular toxicity and can rapidly distinguish between NQO1 expressing and -nonexpressing cancer cell lines through phosphorescence imaging. PMID- 26540619 TI - Effective and novel enantioselective preparation of pyranopyrazoles and pyranocoumarins that is catalyzed by a quinine-derived primary amine. AB - In this study, we executed an effective and novel enantioselective Michael/cyclodehydration sequential reaction between pyrazolin-5-one (or 4 hydroxy-2-pyrone) and chalcones that is catalyzed by a quinine-derived primary amine L7 in the presence of Boc-D-Phg-OH. Chiral pyranopyrazoles and pyranocoumarins were obtained in excellent enantioselectivities (up to 93%) with moderate yields and moderate enantioselectivities with high yields (up to 84%). PMID- 26540618 TI - Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation in a non-human primate model of collagen-induced arthritis. AB - T cells have a central pathogenic role in the aetiopathogenesis of rheumatoid arthritis (RA), and are therefore a favoured target of immunotherapy aiming at physical or functional elimination. Here we report an efficacy test of FR104, a new co-stimulation inhibitor directly targeting CD28 on T cells, in a translationally relevant model, the rhesus monkey model of collagen-induced arthritis (CIA). As a relevant comparator we used abatacept [cytotoxic T lymphocyte antigen immunoglobulin (CTLA Ig)], an antagonist of CTLA-4 binding to CD80/86 clinically approved for treatment of RA. Treatment with either compound was started at the day of CIA induction. Although FR104 previously demonstrated a higher control of T cell responses in vitro than abatacept, both compounds were equally potent in the suppression of CIA symptoms and biomarkers, such as the production of C-reactive protein (CRP) and interleukin (IL)-6 and anti-collagen type II (CII) serum antibody (IgM/IgG). However, in contrast to abatacept, FR104 showed effective suppression of CII-induced peripheral blood mononuclear cell (PBMC) proliferation. The current study demonstrates a strong potential of the new selective CD28 antagonist FR104 for treatment of RA. PMID- 26540620 TI - Selenide-Based Electrocatalysts and Scaffolds for Water Oxidation Applications. AB - Selenide-based electrocatalysts and scaffolds on carbon cloth are successfully fabricated and demonstrated for enhanced water oxidation applications. A max-imum current density of 97.5 mA cm(-2) at an overpotential of a mere 300 mV and a small Tafel slope of 77 mV dec(-1) are achieved, suggesting the potential of these materials to serve as advanced oxygen evolution reaction catalysts. PMID- 26540621 TI - Enzymatic Glycosylation of Phenolic Antioxidants: Phosphorylase-Mediated Synthesis and Characterization. AB - Although numerous biologically active molecules exist as glycosides in nature, information on the activity, stability, and solubility of glycosylated antioxidants is rather limited to date. In this work, a wide variety of antioxidants were glycosylated using different phosphorylase enzymes. The resulting antioxidant library, containing alpha/beta-glucosides, different regioisomers, cellobiosides, and cellotriosides, was then characterized. Glycosylation was found to significantly increase the solubility and stability of all evaluated compounds. Despite decreased radical-scavenging abilities, most glycosides were identified to be potent antioxidants, outperforming the commonly used 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT). Moreover, the point of attachment, the anomeric configuration, and the glycosidic chain length were found to influence the properties of these phenolic glycosides. PMID- 26540622 TI - Discontent and Confusion: Primary Care Providers' Opinions and Understanding of Current Cervical Cancer Screening Recommendations. AB - BACKGROUND: In 2012, new cervical cancer screening guidelines were published by three widely recognized entities which advocate delayed onset of testing, fewer screenings, selective use of human papilloma virus co-testing, and no further screening in women over age 65 years. Early observations report that these recommendations are not being followed and overscreening is common. This study seeks to understand why primary care providers might not adhere to these new 'best practice' health policy protocols. METHODS: A total of 4,909 randomly selected primary care providers (physicians, nurse practitioners, and physician assistants) practicing in California were mailed a study questionnaire. Participants were asked if they consider current published screening guidelines to be authoritative, reliable, and/or clinically appropriate. Clinical vignettes captured individual provider beliefs on timing and method of cervical cancer screening in women within the four key age groups embedded in current screening guidelines. RESULTS: Of the 4,909 surveys mailed, 1,268 (25.8%) qualified responses were received. Fundamentally, 35.0% of all primary care providers do not believe current guidelines are clinically appropriate, with 58.6% of obstetrician/gynecologist physicians having this same skepticism. Even among those who affirmatively believe current guidelines are authoritative, reliable, and clinically appropriate, only 15.3% recommend screening intervals and methodology of testing in women of four differing ages consistent with that of current policy guidelines. CONCLUSION: Among the primary care providers surveyed, distrust and confusion likely limit adherence to current evidence-based cervical cancer screening health policy recommendations, and contribute to the current high rates of overscreening that have been observed. PMID- 26540623 TI - Effect of temperature and water activity on gene expression and aflatoxin biosynthesis in Aspergillus flavus on almond medium. AB - Almonds are among the commodities at risk of aflatoxin contamination by Aspergillus flavus. Temperature and water activity are the two key determinants in pre and post-harvest environments influencing both the rate of fungal spoilage and aflatoxin production. Varying the combination of these parameters can completely inhibit or fully activate the biosynthesis of aflatoxin, so it is fundamental to know which combinations can control or be conducive to aflatoxin contamination. Little information is available about the influence of these parameters on aflatoxin production on almonds. The objective of this study was to determine the influence of different combinations of temperature (20 degrees C, 28 degrees C, and 37 degrees C) and water activity (0.90, 0.93, 0.96, 0.99 aw) on growth, aflatoxin B1 (AFB1) production and expression of the two regulatory genes, aflR and aflS, and two structural genes, aflD and aflO, of the aflatoxin biosynthetic cluster in A. flavus grown on an almond medium solidified with agar. Maximum accumulation of fungal biomass and AFB1 production was obtained at 28 degrees C and 0.96 aw; no fungal growth and AFB1 production were observed at 20 degrees C at the driest tested conditions (0.90 and 0.93 aw). At 20 degrees and 37 degrees C AFB1 production was 70-90% lower or completely suppressed, depending on aw. Reverse transcriptase quantitative PCR showed that the two regulatory genes (aflR and aflS) were highly expressed at maximum (28 degrees C) and minimum (20 degrees C and 37 degrees C) AFB1 production. Conversely the two structural genes (aflD and aflO) were highly expressed only at maximum AFB1 production (28 degrees C and 0.96-0.99 aw). It seems that temperature acts as a key factor influencing aflatoxin production which is strictly correlated to the induction of expression of structural biosynthesis genes (aflD and aflO), but not to that of aflatoxin regulatory genes (aflR and aflS), whose functional products are most likely subordinated to other regulatory processes acting at post translational level. The results of this study are useful to select conditions that could be used in the almond processing chain to suppress aflatoxin production in this important product. PMID- 26540625 TI - Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend((r)) SF PH4 oral suspensions. AB - The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend((r)) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 degrees C) and controlled room temperature (20-25 degrees C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes. PMID- 26540626 TI - Characterizations of the hydrolyzed products of ginkgolide A and ginkgolide B by liquid chromatography coupled with mass spectrometry. AB - Ginkgolides are diterpenoid trilactones responsible for the neuromodulatory properties of Ginkgo biloba extracts. They are to be hydrolyzed in aqueous solutions as mixed carboxylate forms potentially including three monocarboxylates, three dicarboxylates and one tricarboxylate. Characterizations of the hydrolyzed products are challenging because there is no way to prepare them individually. In this work, the major hydrolyzed products of ginkgolide A (GA) and ginkgolide B (GB) including all three monocarboxyaltes have been produced in buffers and subjected to liquid chromatography coupled with triple quadrupole MS and LTQ Orbitrap MS analysis. With the comparative analysis of the trilactone of GA and GB, it was highlighted a unique charge-driven fragmentation pathway of twice neutral losses of CO on the lactone-C. The monocarboxylates were accordingly identified based on the construction of their fragmentation pathways cross-linked with those of the trilactone. In brief, the lactone-C hydrolyzed product is characteristic of the absence of product ions between [M-H](-) and [M H-C2H2O3](-) (m/z 351 for GA and m/z 367 for GB). The featured fragmentation pathway of the lactone-F hydrolyzed product is the cleavage of ring-A, yielding a fragment (m/z 295 for GA and m/z 309 for GB) followed with twice (GA) or triple (GB) neutral losses of CO. The most characteristic fragment of the lactone-E hydrolyzed product is [M-H-H2O-CO2-2CO](-) (m/z 307 for GA and m/z 323 for GB) in contrast to the other two monocarboxylates. The knowledge gained in this work was of special uses to investigate the biological fates and the corresponding pharmacological mechanisms of ginkgolides. PMID- 26540627 TI - Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol metabolite in plasma and its application in mouse pharmacokinetic studies. AB - A validated simple, fast and sensitive bio-analytical assay for ibrutinib and its dihydrodiol metabolite in human and mouse plasma was set up. Sample preparation was performed by protein precipitation, and addition of the respective deuterated internal standards, followed by LC-MS/MS analysis. Separation was performed on a 3.5 MUm particle-size, bridged ethylene hybrid column with gradient elution by 0.1% v/v formic acid and acetonitrile. The full eluate was transferred to an electrospray interface in positive ionization mode, and subsequently analyzed by a triple quadrupole mass spectrometer by selected reaction monitoring. The assay was validated in a 5-5000 ng/ml calibration range. Both ibrutinib and dihydrodiol ibrutinib were deemed stable under refrigerated or frozen storage conditions. At room temperature, ibrutinib showed a not earlier described instability, and revealed rapid degradation at 37 degrees C. Finally, the assay was used for a pharmacokinetic study of plasma levels in treated FVB mice. PMID- 26540628 TI - Quantification of reactive carbonyl compounds in icodextrin-based peritoneal dialysis fluids by combined UHPLC-DAD and -MS/MS detection. AB - During heat sterilization of peritoneal dialysis (PD) fluids, the glucose component is partially degraded. The formed glucose degradation products impair biocompatibility and limit the long-term application of PD fluids. As an alternative to glucose, icodextrin, a polyglucose, is used as osmotic agent in PD fluids. After targeted screening for reactive carbonyl compounds, NMR- and MS analyses very recently revealed 4-deoxyglucosone (4-DG), 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxypentosone (3,4-DDPS), and 5 hydroxymethylfurfural (5-HMF) as main polyglucose degradation products (pGDPs) in icodextrin-based PD fluids. Now, the present study established and validated a UHPLC method with DAD as well as a UHPLC-MS/MS method for the first-time quantification of those five major pGDPs in commercial icodextrin PD fluids after derivatization with o-phenylenediamine. Thus, 4-DG was identified to be the main degradation product (in concentrations up to 20 MUM). In contrast to the values measured in glucose-based products, the concentration of 3-DGal (<= 16 MUM) was higher than the concentration of 3-DG (<= 7 MUM) indicating different reaction pathways starting from polyglucose compared to glucose. The compounds 3,4-DDPS and 5-HMF were present in minor quantities (<= 0.3 MUM each). PMID- 26540629 TI - Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway. AB - Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells. PMID- 26540630 TI - Insulin-like growth factor-independent insulin-like growth factor binding protein 3 promotes cell migration and lymph node metastasis of oral squamous cell carcinoma cells by requirement of integrin beta1. AB - Frequent metastasis to the cervical lymph nodes leads to poor survival of patients with oral squamous cell carcinoma (OSCC). To understand the underlying mechanisms of lymph node metastasis, two sublines were successfully isolated from cervical lymph nodes of nude mice through in vivo selection, and identified as originating from poorly metastatic parental cells. These two sublines specifically metastasized to cervical lymph nodes in 83% of mice, whereas OEC-M1 cells did not metastasize after injection into the oral cavity. After gene expression analysis, we identified insulin-like growth factor binding protein 3 (IGFBP3) as one of the significantly up-regulated genes in the sublines in comparison with their parental cells. Consistently, meta-analysis of the public microarray datasets and IGFBP3 immunohistochemical analysis revealed increased both levels of IGFBP3 mRNA and protein in human OSCC tissues when compared to normal oral or adjacent nontumorous tissues. Interestingly, the up-regulated IGFBP3 mRNA expression was significantly associated with OSCC patients with lymph node metastasis. IGFBP3 knockdown in the sublines impaired and ectopic IGFBP3 expression in the parental cells promoted migration, transendothelial migration and lymph node metastasis of orthotopic transplantation. Additionally, ectopic expression of IGFBP3 with an IGF-binding defect sustained the IGFBP3-enhanced biological functions. Results indicated that IGFBP3 regulates metastasis-related functions of OSCC cells through an IGF-independent mechanism. Furthermore, exogenous IGFBP3 was sufficient to induce cell motility and extracellular signal regulated kinase (ERK) activation. The silencing of integrin beta1 was able to impair exogenous IGFBP3-mediated migration and ERK phosphorylation, suggesting a critical role of integrin beta1 in IGFBP3-enchanced functions. PMID- 26540631 TI - Integrative analysis to select cancer candidate biomarkers to targeted validation. AB - Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID- 26540632 TI - SOX2 boosts major tumor progression genes in prostate cancer and is a functional biomarker of lymph node metastasis. AB - Critical issues in prostate cancer (PC) are a. identification of molecular drivers of the highly aggressive neuroendocrine differentiation (NED) in adenocarcinoma, and b. early assessment of disease progression. The SRY (sex determining region Y)-box 2 gene, SOX2, is an essential embryonic stem cell gene involved in prostate tumorigenesis. Here we assessed its implications in NED and progression of PC and its diagnostic and prognostic value. Laser microdissection, qRT-PCR, quantitative Methylation-Specific PCR and immunohistochemistry were used to analyze SOX2 gene expression and regulation in 206 PC samples. Results were examined according to the patient's clinical pathological profile and follow-ups. Functional studies were performed using PC cells transfected to overexpress or silence SOX2. SOX2 was consistently downregulated in PC, except in cell clusters lying within lymph node (LN)-positive PC. Multivariate analysis revealed that SOX2 mRNA expression in the primary tumor was significantly associated with LN metastasis. When SOX2 mRNA levels were >=1.00, relative to (XpressRef) Universal Total RNA, adjusted Odds Ratio was 24.4 (95% CI: 7.54-79.0), sensitivity 0.81 (95% CI: 0.61-0.93) and specificity 0.87 (95% CI: 0.81-0.91). Patients experiencing biochemical recurrence had high median levels of SOX2 mRNA. In both PC and LN metastasis, SOX2 and NED marker, Chromogranin-A, were primarily co expressed. In PC cells, NED genes were upregulated by SOX2 overexpression and downregulated by its silencing, which also abolished SNAI2/Slug dependent NED. Moreover, SOX2 upregulated neural CAMs, neurotrophins/neurotrophin receptors, pluripotency and epithelial-mesenchymal transition transcription factors, growth, angiogenic and lymphangiogenic factors, and promoted PC cell invasiveness and motility. This study discloses novel SOX2 target genes driving NED and spread of PC and proposes SOX2 as a functional biomarker of LN metastasization for PC. PMID- 26540635 TI - Core-Shell, Ultrasmall Particles, Monoliths, and Other Support Materials in High Performance Liquid Chromatography. PMID- 26540634 TI - Circannual variation of efficacy outcomes in patients with newly diagnosed metastatic colorectal cancer and treated with first-line chemotherapy. AB - Seasonal variation of baseline diagnosis (or clinical suspect) of stage I-III colorectal cancer patients has been repeatedly reported as an independent variable influencing overall survival. However, data are conflicting and no information is available about such a rhythm in advanced stage patients. To test whether a circannual rhythm of efficacy outcomes can be detected in this setting, we collected data about response rate (RR), progression-free survival (PFS), and overall survival (OS) to first-line chemotherapy of 1610 newly diagnosed metastatic patients treated at four independent centers. Responses to first-line chemotherapy were available for 1495 patients. A strong circannual rhythm in RR was evident, with the higher proportion of responding patients in the subgroup diagnosed in January (acrophase). At the time of data cutoff, 1322 patients progressed and 986 died, with median PFS and OS of 11 and 25.6 months, respectively. A circannual rhythmicity of the proportion of patients progressing at 6 months and surviving at 1 year was demonstrated, with acrophases located both in winter (February and January, respectively), similar to what reported for RR. Several interpretations about the genesis of this cyclic variation could be claimed: the rhythm in sunlight exposure and, as a consequence, of vitamin D serum levels and folate degradation, the variability in toxic effect intensity of chemotherapy, and the rhythm in the biological behavior of tumor cells. This observation is worth of further investigation both in preclinical and in clinical settings in order to better elucidate the underlying mechanisms. PMID- 26540633 TI - Long non-coding RNA HULC promotes tumor angiogenesis in liver cancer by up regulating sphingosine kinase 1 (SPHK1). AB - Highly up-regulated in liver cancer (HULC) is a long non-coding RNA (lncRNA). We found that HULC up-regulated sphingosine kinase 1 (SPHK1), which is involved in tumor angiogenesis. Levels of HULC were positively correlated with levels of SPHK1 and its product, sphingosine-1-phosphate (S1P), in patients HCC samples. HULC increased SPHK1 in hepatoma cells. Chicken chorioallantoic membrane (CAM) assays revealed that si-SPHK1 remarkably blocked the HULC-enhanced angiogenesis. Mechanistically, HULC activated the promoter of SPHK1 in hepatoma cells through the transcription factor E2F1. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) further showed that E2F1 was capable of binding to the E2F1 element in the SPHK1 promoter. HULC increased the expression of E2F1 in hepatoma cells and levels of HULC were positively correlated with those of E2F1 in HCC tissues. Intriguingly, HULC sequestered miR 107, which targeted E2F1 mRNA 3'UTR, by complementary base pairing. Functionally, si-SPHK1 remarkably abolished the HULC-enhanced tumor angiogenesis in vitro and in vivo. Taken together, we conclude that HULC promotes tumor angiogenesis in liver cancer through miR-107/E2F1/SPHK1 signaling. Our finding provides new insights into the mechanism of tumor angiogenesis. PMID- 26540636 TI - Periorbital Necrotizing Fasciitis Following Dexamethasone Intravitreal Implant Injection. PMID- 26540637 TI - The complete mitochondrial DNA genome of Gymnodiptychus dybowskii (Cypriniformes: Cyprinidae: Schizothoracinae). AB - The complete nucleotide sequence of Gymnodiptychus dybowskii mitogenome (16 677 bp) has been determined, containing 13 protein-coding genes, two ribosomal RNA genes, 22 tRNA genes, and one non-coding control region. The base composition is 28.04% A, 26.92% T, 18.94% G, 26.10% C, with an AT bias of 54.97%. The origin of light-strand replication (OL) is found between tRNAAsn and tRNACys, which has the potential to fold in a step-loop secondary structure with a stem formed by 11 pairs of nucleotides and a loop of 14 nucleotides. The phylogenetic analysis indicates close relationship between genus Gymnodiptychus and Diptychus. PMID- 26540638 TI - World Pneumonia Day - November 12, 2015. PMID- 26540639 TI - Increased microalbuminuria prevalence among patients with nonalcoholic fatty liver disease. AB - AIM: To determine the prevalence of microalbuminuria, that is an indirect predictor of coronary artery disease, among non-obese and non-diabetic patients with fatty liver disease. MATERIAL AND METHOD: This retrospective study was carried out on non-obese (body mass index (BMI) < 30) and non-diabetic 290 female and 189 male, totally 479 cases. All subjects underwent liver ultrasonography scanning to determine the presence and stage of fatty liver disease. RESULTS: The subjects were grouped according to the ultrasound findings as follows: 182 (37.9%) cases without any fat accumulation in liver were regarded as control group; and among remaining cases, 124 (25.8%) had mild, 93 (19.4%) had moderate, and 80 (16.7%) had severe fatty liver disease. There was not any statistically significant difference between groups in regards to the age, gender, liver function tests, renal function tests or glomerular filtration rate. However urinary protein/creatinine ratio was statistically significantly higher in severe nonalcoholic fatty liver disease (NAFLD) group than the other three groups. In moderate and severe NAFLD groups, microalbuminuria was statistically significantly more common compared with the control and mild NAFLD groups. Regarding the results of multiple logistic regression analysis, presence of fatty liver disease increased the risk of microalbuminuria for 1.87 times independently from increased BMI and increased HOMA-IR values. CONCLUSION: We have determined that microalbuminuria is more prevalent among NAFLD cases compared with control cases and microalbuminuria prevalence was increasing with the advanced stages of NAFLD although two main etiologic factors of microalbuminuria, type 2 diabetes, and obesity were excluded. PMID- 26540640 TI - Investigation of the index case herd and identification of the genotypes of Theileria orientalis associated with outbreaks of bovine anaemia in New Zealand in 2012. AB - CASE HISTORY AND CLINICAL FINDINGS: On 7 September 2012 the Ministry for Primary Industries was notified of a dairy cow with regenerative anaemia (haematocrit (HCT) 0.08 L/L) in a herd of 465 Jersey-Friesian cross cows (index case herd) in the Northland region of New Zealand. Organisms consistent with Theileria spp. were present in red blood cells on a blood smear. No other causes of anaemia were detected following examination of affected cows. Blood samples collected from 29 randomly selected cows on 26 September 2012 showed that 24 (83%) were anaemic (HCT<=0.24 L/L) and therefore fitted the case definition for bovine anaemia associated with Theileria orientalis infection. LABORATORY FINDINGS: Using a T. orientalis type-specific PCR assay that targeted the single subunit rRNA gene, all of six animals tested were positive for T. orientalis type Ikeda. Blood samples collected from clinically affected cattle in 11 subsequent outbreaks from throughout the North Island showed that T. orientalis Ikeda type was a common finding, but mixed infections with Chitose type were also identified. In addition, using a PCR assay that targeted the major piroplasm surface gene, T. orientalis type 5 was detected in one cow from the Waikato region. DIAGNOSIS: The presence of T. orientalis type Ikeda, as well as type 5, was confirmed in cattle from outbreaks of bovine anaemia in herds throughout the North Island of New Zealand. CLINICAL RELEVANCE: Two new types of T. orientalis were identified in this investigation, that were associated with a sudden rise in cases of bovine anaemia. The body of evidence showed that the Ikeda type was implicated as the cause of disease observed in this epidemic. PMID- 26540641 TI - Epidemiology and molecular mechanism of frontotemporal lobar degeneration/amyotrophic lateral sclerosis with repeat expansion mutation in C9orf72. AB - GGGGCC hexanucleotide repeat expansions in C9orf72 were identified in 2011 as the genetic cause of frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS) linked to chromosome 9. Since then, a number of studies have been conducted to delineate the molecular epidemiology of the repeat expansions and the molecular pathophysiology of the disease. The frequency of the repeat expansions considerably varied among countries. The frequency of the repeat expansions was high in European populations and populations of European descent and a substantial proportion of sporadic FTLD or ALS patients also have the mutations in these populations. On the other hand, the frequency was extremely low in Asia or Oceania except for limited regions including Kii Peninsula of Japan. A founder effect seems to strongly influence the regional differences in the frequency, but there is no definitive evidence that supports the notion that the repeat expansions arose in a single founder or multiple founders. As a disease-causing mechanism, several molecular mechanisms have been proposed, including conformational changes of DNA (G-quadruplex formation and hypermethylation) or RNA (G-quadruplex formation) molecules, altered transcriptional levels of C9orf72, sequestration of RNA-binding proteins, bidirectional transcription, formation of RNA foci, and neurotoxicity of dipeptide repeat proteins generated by repeat-associated non-ATG-initiated translation. Further investigations on the molecular mechanisms of neurodegeneration are expected to lead to the development of therapeutic interventions for this disease as well as for other diseases associated with non coding repeat expansions. PMID- 26540642 TI - A framework for telepsychiatric training and e-health: Competency-based education, evaluation and implications. AB - Telepsychiatry (TP; video; synchronous) is effective, well received and a standard way to practice. Best practices in TP education, but not its desired outcomes, have been published. This paper proposes competencies for trainees and clinicians, with TP situated within the broader landscape of e-mental health (e MH) care. TP competencies are organized using the US Accreditation Council of Graduate Medical Education framework, with input from the CanMEDS framework. Teaching and assessment methods are aligned with target competencies, learning contexts, and evaluation options. Case examples help to apply concepts to clinical and institutional contexts. Competencies can be identified, measured and evaluated. Novice or advanced beginner, competent/proficient, and expert levels were outlined. Andragogical (i.e. pedagogical) methods are used in clinical care, seminar, and other educational contexts. Cross-sectional and longitudinal evaluation using quantitative and qualitative measures promotes skills development via iterative feedback from patients, trainees, and faculty staff. TP and e-MH care significantly overlap, such that institutional leaders may use a common approach for change management and an e-platform to prioritize resources. TP training and assessment methods need to be implemented and evaluated. Institutional approaches to patient care, education, faculty development, and funding also need to be studied. PMID- 26540643 TI - Human papillomavirus detected in viral warts of renal transplant recipients. AB - OBJECTIVES: Few studies have been conducted in South America regarding the detection and genotyping of human papillomavirus (HPV) in viral warts of renal transplant recipients (RTRs). The characterization of the population most susceptible to the development of warts and the knowledge of the main HPV types in this environment prompted this study, which focuses on the detection and typing of HPV in RTRs in Brazil. METHODS: Fifty-eight patients with viral warts from the Hospital Sao Paulo/Federal University of Sao Paulo were included in this study. HPV was detected by polymerase chain reaction (PCR) using combinations of the following primers: PGMY 09/11, RK 91, CP 65/70, and CP 66/69. Restriction fragment length polymorphism and automated sequencing techniques were used for HPV typing. RESULTS: HPV was detected by PCR in 89.7% of viral wart samples. The most frequently detected HPV types included 57, 27, 1a, 2a, and 20. Other types of HPV-epidermodysplasia verruciformis were also detected, including 14, 15, 19, 20, 21, 23, 36, and 38. Rare HPV types were also detected in our environment, including RTR X1, RTR X7, and 100. The time after transplant was correlated with an increased number of lesions and beta papillomavirus genus infection. CONCLUSIONS: The HPV types detected in the RTR population were similar to those described in immunocompetent populations. However, the diversity of the HPV types identified and the number of lesions were increased in the RTR population. PMID- 26540644 TI - Complete mitochondrial genome of Camptochilus aurea (Lepidoptera: Thyrididae). AB - The complete mitochondrial genome of Camptochilus aurea (Butler, 1881) has been determined. The entire mitochondrial genome of C. aurea is 15 362bp in length which contains 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes and a control region. Twelve PCGs of C. aurea start with ATN codon, but the COI gene uses CGA as the start codon. Inferred phylogenetic relationships based on the data of 25 Lepidoptera species using Bayesian inference method indicated Thyrididae had a close relationship with Gelechioidea. PMID- 26540646 TI - Resistive Switching of Individual, Chemically Synthesized TiO2 Nanoparticles. AB - Resistively switching devices are considered promising for next-generation nonvolatile random-access memories. Today, such memories are fabricated by means of "top-down approaches" applying thin films sandwiched between nanoscaled electrodes. In contrast, this work presents a "bottom-up approach" disclosing for the first time the resistive switching (RS) of individual TiO2 nanoparticles (NPs). The NPs, which have sizes of 80 and 350 nm, respectively, are obtained by wet chemical synthesis and thermally treated under oxidizing or vacuum conditions for crystallization, respectively. These NPs are deposited on a Pt/Ir bottom electrode and individual NPs are electrically characterized by means of a nanomanipulator system in situ, in a scanning electron microscope. While amorphous NPs and calcined NPs reveal no switching hysteresis, a very interesting behavior is found for the vacuum-annealed, crystalline TiO(2-x) NPs. These NPs reveal forming-free RS behavior, dominantly complementary switching (CS) and, to a small degree, bipolar switching (BS) characteristics. In contrast, similarly vacuum-annealed TiO2 thin films grown by atomic layer deposition show standard BS behavior under the same conditions. The interesting CS behavior of the TiO(2-x) NPs is attributed to the formation of a core-shell-like structure by re-oxidation of the reduced NPs as a unique feature. PMID- 26540645 TI - Mind-Body Approaches to Treating Mental Health Symptoms Among Disadvantaged Populations: A Comprehensive Review. AB - Mind-body approaches are commonly used to treat a variety of chronic health conditions, including depression and anxiety. A substantial proportion of individuals with depression and anxiety disorders do not receive conventional treatment; disadvantaged individuals are especially unlikely to receive treatment. Mind-body approaches offer a potentially more accessible and acceptable alternative to conventional mental health treatment for disadvantaged individuals, who may not otherwise receive mental health treatment. This review examines evidence for the efficacy of mind-body interventions for mental health symptoms among disadvantaged populations. While rates of utilization were relatively lower for racial/ethnic minorities, evidence suggests that significant proportions of racial/ethnic minorities are using complementary health approaches as health treatments, especially prayer/healers and natural or herbal remedies. This review of studies on the efficacy of mind-body interventions among disadvantaged populations found evidence for the efficacy of mind-body approaches for several mental and physical health symptoms, functioning, self-care, and overall quality of life. PMID- 26540647 TI - Postmastectomy Radiation Therapy and Breast Reconstruction--Marching Forward Together or Apart? PMID- 26540649 TI - In situ analysis of copper electrodeposition reaction using unilateral NMR sensor. AB - The uses of high-resolution NMR spectroscopy and imaging (MRI) to study electrochemical reactions in situ have greatly increased in the last decade. However, most of these applications are limited to specialized NMR laboratories and not feasible for routine analysis. Recently we have shown that a bench top, time domain NMR spectrometer can be used to monitor in situ copper electrodeposition reaction and the effect of Lorentz force in the reaction rate. However these spectrometers limit the cell size to the magnet gap and cannot be used with standard electrochemical cells. In this paper we are demonstrating that unilateral NMR sensor (UNMR), which does not limit sample size/volume, can be used to monitor electrodeposition of paramagnetic ions in situ. The copper electrodeposition reaction was monitored remotely and in situ, placing the electrochemical cell on top of the UNMR sensor. The Cu(2+) concentration was measured during three hours of the electrodeposition reactions, by using the transverse relaxation rate (R2) determined with the Carr-Purcell-Meiboom-Gill pulse sequence. The reaction rate increased fourfold when the reaction was performed in the presence of a magnetic field (in situ), in comparison to the reactions in the absence of the magnetic field (ex situ). The increase of reaction rate, in the presence of the UNMR magnet, was related to the magneto hydrodynamic force (FB) and magnetic field gradient force (F?B). F?B was calculated to be one order of magnitude stronger than FB. The UNMR sensor has several advantages for in situ measurements when compared to standard NMR spectrometers. It is a low cost, portable, open system, which does not limit sample size/volume and can be easily be adapted to standard electrochemical cells or large industrial reactors. PMID- 26540650 TI - Transport and imaging of brute-force (13)C hyperpolarization. AB - We demonstrate transport of hyperpolarized frozen 1-(13)C pyruvic acid from its site of production to a nearby facility, where a time series of (13)C images was acquired from the aqueous dissolution product. Transportability is tied to the hyperpolarization (HP) method we employ, which omits radical electron species used in other approaches that would otherwise relax away the HP before reaching the imaging center. In particular, we attained (13)C HP by 'brute-force', i.e., using only low temperature and high-field (e.g., T<~2K and B~14T) to pre-polarize protons to a large Boltzmann value (~0.4% (1)H polarization). After polarizing the neat, frozen sample, ejection quickly (<1s) passed it through a low field (B<100G) to establish the (1)H pre-polarization spin temperature on (13)C via the process known as low-field thermal mixing (yielding ~0.1% (13)C polarization). By avoiding polarization agents (a.k.a. relaxation agents) that are needed to hyperpolarize by the competing method of dissolution dynamic nuclear polarization (d-DNP), the (13)C relaxation time was sufficient to transport the sample for ~10min before finally dissolving in warm water and obtaining a (13)C image of the hyperpolarized, dilute, aqueous product (~0.01% (13)C polarization, a >100-fold gain over thermal signals in the 1T scanner). An annealing step, prior to polarizing the sample, was also key for increasing T1~30-fold during transport. In that time, HP was maintained using only modest cryogenics and field (T~60K and B=1.3T), for T1((13)C) near 5min. Much greater time and distance (with much smaller losses) may be covered using more-complete annealing and only slight improvements on transport conditions (e.g., yielding T1~5h at 30K, 2T), whereas even intercity transfer is possible (T1>20h) at reasonable conditions of 6K and 2T. Finally, it is possible to increase the overall enhancement near d-DNP levels (i.e., 10(2)-fold more) by polarizing below 100mK, where nanoparticle agents are known to hasten T1 buildup by 100-fold, and to yield very little impact on T1 losses at temperatures relevant to transport. PMID- 26540648 TI - Combining CRISPR/Cas9 and rAAV Templates for Efficient Gene Editing. AB - Altering endogenous genes in cells is an integral tool of modern cell biology. The ease-of-use of the CRISPR/Cas9 system to introduce genomic DNA breaks at specific sites in vivo has led to its rapid and wide adoption. In the absence of a DNA template, the lesion is repaired by nonhomologous end joining resolving as internal deletions. However, in the presence of a homologous DNA template, homology-directed repair occurs with variable efficiencies. Recent work has demonstrated that highly efficient gene targeting can be induced by combining CRISPR/Cas9 targeting of genomic loci with recombinant adeno-associated virus (rAAV) to provide a single-stranded homologous DNA template. Here we review the current state of CRISPR/Cas-based gene editing and provide a practical guide to applying the CRISPR/Cas and rAAV system for highly efficient, time- and cost effective gene targeting. PMID- 26540652 TI - Do the Effects of Transcutaneous Electrical Nerve Stimulation on Knee Osteoarthritis Pain and Function Last? AB - Transcutaneous electrical nerve stimulation (TENS) has been shown to decrease pain associated with knee osteoarthritis, which potentially leads to better function, improved quality of life, and postpones the need for surgical intervention. The purpose of this study was to perform a 1-year follow-up of a previous prospective group of patients with knee osteoarthritis, randomized to TENS or standard of care, who were asked to rate their changes in: (1) patient pain perception; (2) subjective medication use; (3) subjective functional abilities; (4) quality of life; (5) device use; and (6) conversion to TKA. A population of 70 patients were randomized to receive either a TENS device or a standard conservative therapy regimen. Patients were evaluated based on various subjective outcomes at minimum 1-year (mean, 19 months) follow-up. The TENS cohort had lower visual analog pain scores compared with the matching cohort. Subjective functional outcomes, as well as functional and activity scores, were also greater in the TENS cohort. Patients in TENS cohort showed significant improvements in their subjective and functional outcomes as compared with their initial status, while the control group did not show significant change. A majority of the TENS patients were able to reduce the amount of pain medications. Additionally, a large portion of the patients assigned to the TENS group continue to use the device, after completion of the trial. This study demonstrated the benefit of TENS for improving subjective outcomes in patients with pain due to knee osteoarthritis, compared with standard conservative treatments. The results of the study suggest that TENS is a safe and effective adjunct as part of the spectrum of current nonoperative treatment methods for knee osteoarthritis. PMID- 26540651 TI - Association Between KCNQ1 Genetic Variants and Type 2 Diabetes in the Uyghur Population. AB - OBJECTIVE: To investigate the association between KCNQ1 gene polymorphisms and type 2 diabetes (T2D) in an admixed ethnic minority, Uyghur population, living in the Northwest region of China. MATERIALS AND METHODS: We genotyped three tagging single-nucleotide polymorphisms rs2283171, rs11023485, and rs2283208 of the KCNQ1 gene in 1006 T2D participants and 1004 controls and conducted association analysis. RESULTS: The frequencies of the AG and GG genotypes and the G allele of rs2283171 were higher in the control group (51.4%, 22%, and 47.7%, respectively) than in the case group (49%, 17.6%, and 42.1%, respectively). The minor G allele decreased the risk of T2D with a per-allele odds ratio of 0.79 (95% CI: 0.70 0.90) for the additive genetic model in univariate analysis (p = 0.0001). After adjustment for the covariates of age, gender, smoking, alcohol use, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), and total cholesterol (TC), the diabetic protective effect of the rs2283171-G allele remained. No difference was observed in the frequency distributions of the rs11023485 and rs2283208 genotypes between the two groups. CONCLUSION: We identified a novel association between rs2283171 of KCNQ1 and T2D in the Uyghur population. Further association and functional studies are required to identify the causal functional variant that is in linkage disequilibrium with this polymorphism. PMID- 26540653 TI - Impact of Use of Intramedullary and Extramedullary Guides on Tibial Component Geometry in Total Knee Replacements: A Systematic Review and Meta-Analysis. AB - Mechanical guides in total knee arthroplasty are divided into intramedullary and extramedullary systems, designed to give accurate reference, to enable the surgeon to perform a tibial cut which is perpendicular to the mechanical axis. We conducted a systematic review and meta-analysis of levels 1 and 2 published data which directly compares the two methods of alignment, with outcomes of interest being the mean tibial component angle to the mechanical axis and the number of outliers from the optimal range. The PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidance was followed. A search was conducted of online databases Medline PubMed; EMBASE; ISI Web of Science, and the Cochrane library, using the Boolean search string ([intramedullary OR extramedullary] AND knee AND [arthroplasty OR replacement]). Numerical data pertaining to tibial component alignment (TCA), the mechanical tibiofemoral angle, the tibial slope, and the number of outliers from optimal TCA were collated, and used to establish pooled results. No constraints on the search in terms of year of publication or language were instituted. Intrastudy bias was assessed using the Jadad score for randomized controlled trials and the Newcastle Ottawa score for prospective cohort studies. A total of 1,896 titles were reviewed. Following abstract review and full review of relevant articles, 10 publications were included for analysis, of which 8 were suitable to include for meta-analysis. No trials showed a significant difference in the mean TCA. Two trials showed an increased number of outliers in the extramedullary group and two studies showed an increased number of outliers in the intramedullary group. Pooled data from studies which included these outcomes showed no advantage for either system in limiting the number of outliers from the optimal TCA (relative risk, 0.99; 95% confidence interval [CI], 0.87-1.14; p = 0.004), and no significant difference in mean TCA (standardized mean difference, -0.07; 95% CI, 0.22 to 0.08; p = 0.000). Based on our results, no advantage can be attributed to the type of mechanical guide used in obtaining an adequate tibial cut. PMID- 26540655 TI - Objective Analysis of Performance of Activities of Daily Living in People With Central Field Loss. AB - PURPOSE: People with central visual field loss (CFL) adopt various strategies to complete activities of daily living (ADL). Using objective movement analysis, we compared how three ADLs were completed by people with CFL compared with age matched, visually healthy individuals. METHODS: Fourteen participants with CFL (age 81 +/- 10 years) and 10 age-matched, visually healthy (age 75 +/- 5 years) participated. Three ADLs were assessed: pick up food from a plate, pour liquid from a bottle, and insert a key in a lock. Participants with CFL completed each ADL habitually (as they would in their home). Data were compared with visually healthy participants who were asked to complete the tasks as they would normally, but under specified experimental conditions. Movement kinematics were compared using three-dimension motion analysis (Vicon). Visual functions (distance and near acuities, contrast sensitivity, visual fields) were recorded. RESULTS: All CFL participants were able to complete each ADL. However, participants with CFL demonstrated significantly (P < 0.05) longer overall movement times, shorter minimum viewing distance, and, for two of the three ADL tasks, needed more online corrections in the latter part of the movement. CONCLUSIONS: Results indicate that, despite the adoption of various habitual strategies, participants with CFL still do not perform common daily living tasks as efficiently as healthy subjects. Although indices suggesting feed-forward planning are similar, they made more movement corrections and increased time for the latter portion of the action, indicating a more cautious/uncertain approach. Various kinematic indices correlated significantly to visual function parameters including visual acuity and midperipheral visual field loss. PMID- 26540654 TI - Human Adult Retinal Pigment Epithelial Stem Cell-Derived RPE Monolayers Exhibit Key Physiological Characteristics of Native Tissue. AB - PURPOSE: We tested what native features have been preserved with a new culture protocol for adult human RPE. METHODS: We cultured RPE from adult human eyes. Standard protocols for immunohistochemistry, electron microscopy, electrophysiology, fluid transport, and ELISA were used. RESULTS: Confluent monolayers of adult human RPE cultures exhibit characteristics of native RPE. Immunohistochemistry demonstrated polarized expression of RPE markers. Electron microscopy illustrated characteristics of native RPE. The mean transepithelial potential (TEP) was 1.19 +/- 0.24 mV (mean +/- SEM, n = 31), apical positive, and the mean transepithelial resistance (RT) was 178.7 +/- 9.9 Omega.cm2 (mean +/- SEM, n = 31). Application of 100 MUM adenosine triphosphate (ATP) apically increased net fluid absorption (Jv) by 6.11 +/- 0.53 MUL.cm2.h-1 (mean +/- SEM, n = 6) and TEP by 0.33 +/- 0.048 mV (mean +/- SEM, n = 25). Gene expression of cultured RPE was comparable to native adult RPE (n = 5); however, native RPE RNA was harvested between 24 and 40 hours after death and, therefore, may not accurately reflect healthy native RPE. Vascular endothelial growth factor secreted preferentially basally 2582 +/- 146 pg/mL/d, compared to an apical secretion of 1548 +/- 162 pg/mL/d (n = 14, P < 0.01), while PEDF preferentially secreted apically 1487 +/- 280 ng/mL/d compared to a basolateral secretion of 864 +/- 132 ng/mL/d (n = 14, P < 0.01). CONCLUSIONS: The new culture model preserves native RPE morphology, electrophysiology, and gene and protein expression patterns, and may be a useful model to study RPE physiology, disease, and transplantation. PMID- 26540656 TI - Corneal Epithelial Immune Dendritic Cell Alterations in Subtypes of Dry Eye Disease: A Pilot In Vivo Confocal Microscopic Study. AB - PURPOSE: To evaluate density and morphology of corneal epithelial immune dendritic cells (DCs) in different subtypes of dry eye disease (DED) using in vivo confocal microscopy (IVCM). METHODS: This retrospective study included 59 eyes of 37 patients with DED and 40 eyes of 20 age-matched healthy controls. Based on clinical tests, eyes with DED were categorized into two subtypes: aqueous-deficient (n = 35) and evaporative (n = 24). For all subjects, images of laser scanning in vivo confocal microscopy (IVCM) of the central cornea were analyzed for DC density and DC morphology (DC size, number of dendrites, and DC field). These DC parameters were compared among all dry eye and control groups. RESULTS: Compared with the controls, patients with DED had significantly higher DC density, larger DC size, higher number of dendrites, and larger DC field (all P < 0.001). Comparison between aqueous-deficient and evaporative subtypes demonstrated that DC density was significantly higher in aqueous-deficient subtype (189.8 +/- 36.9 vs. 58.9 +/- 9.4 cells/mm2, P = 0.001). However, there were no significant differences in morphologic parameters between DED subtypes. When aqueous-deficient DED with underlying systemic immune disease (Sjogren's syndrome and graft versus host disease) were compared with nonimmune conditions, the immunologic subgroup showed significantly higher DC density, DC size, and number of dendrites (all P < 0.05). CONCLUSIONS: Corneal IVCM demonstrated differential changes in DC density and morphologic DC parameters between subtypes of DED. These changes, which reflect the degree of immune activation and inflammation in DED, can be used for clinical practice and endpoints in clinical trials. PMID- 26540658 TI - Active Maintenance of the Gradient of Refractive Index Is Required to Sustain the Optical Properties of the Lens. AB - PURPOSE: To determine whether the cellular physiology of the lens actively maintains the optical properties of the lens and whether inhibition of lens transport affects overall visual quality. METHODS: One lens from a pair of bovine lenses was cultured in artificial aqueous humor (AAH), while the other was cultured in either AAH-High-K+ or AAH + 0.1 mM ouabain for 4 hours. Lens pairs or whole enucleated eyes were then imaged in 4.7 Tesla (T) high-field small animal magnet. Lens surface curvatures, T1 measurements of water content, and T2 measurements of water/protein ratios were extracted from cultured lenses, while the geometrical parameters that define the optical pathway were obtained from whole eyes. Gradients of refractive index (GRIN), calculated from T2 measurements, and the extracted geometric parameters were inputted into optical models of the isolated lens and the whole bovine eye. RESULTS: Inhibiting circulating fluxes by inhibiting the Na/K-ATPase with ouabain or depolarization of the lens potential by High K+ caused changes to lens water content, the water/protein ratio (GRIN) and surface geometry that manifested as an increase in optical power and a decrease in negative spherical aberration in cultured lenses. Changes to optical properties of the lens resulted in a myopic shift that impaired vision quality in the optical model of the bovine eye. CONCLUSIONS: The cellular physiology of the lens actively maintains its optical properties and inhibiting the Na/K/ATPase induces a myopic shift in vision similar to that observed clinically in patients who go on to develop cataract. PMID- 26540657 TI - Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information. AB - PURPOSE: To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. METHODS: We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal prosthesis at frequencies exceeding flicker fusion (>20 Hz). Effects of eye movements on retinal ganglion cell (RGC) activity are simulated using a linear-nonlinear model of the retina. RESULTS: Retinal ganglion cells adapt to high frequency stimulation of constant intensity, and respond transiently to changes in illumination of the implant, exhibiting responses to ON-sets, OFF sets, and both ON- and OFF-sets of light. The percentage of cells with an OFF response decreases with progression of the degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum number of action potentials elicited with prosthetic stimulation is at most half of its natural counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. CONCLUSIONS: Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper delivery of visual information via a subretinal prosthesis. PMID- 26540659 TI - MicroRNA-184 Regulates Corneal Lymphangiogenesis. AB - PURPOSE: MicroRNAs are a class of small noncoding RNAs that negatively regulate gene expression by binding to complimentary sequences of target messenger RNA. Their roles in corneal lymphangiogenesis are largely unknown. This study was to investigate the specific role of microRNA-184 (mir-184) in corneal lymphangiogenesis (LG) in vivo and lymphatic endothelial cells (LECs) in vitro. METHODS: Standard murine suture placement model was used to study the expressional change of mir-184 in corneal inflammatory LG and the effect of synthetic mir-184 mimic on this process. Additionally, a human LEC culture system was used to assess the effect of mir-184 overexpression on cell functions in vitro. RESULTS: Expression of mir-184 was significantly downregulated in corneal LG and, accordingly, its synthetic mimic suppressed corneal lymphatic growth in vivo. Furthermore, mir-184 overexpression in LECs inhibited their functions of adhesion, migration, and tube formation in vitro. CONCLUSIONS: These novel findings indicate that mir-184 is involved critically in LG and potentially could be used as an inhibitor of the process. Further investigation holds the promise for divulging new therapies for LG disorders, which occur inside and outside the eye. PMID- 26540661 TI - Progressive Thinning of Regional Macular Thickness After Epiretinal Membrane Surgery. AB - PURPOSE: To determine the long-term changes in the regional macular thickness after idiopathic epiretinal membrane (ERM) excision and to determine whether there were correlations between the pre- and postoperative central macular thickness and the best-corrected visual acuity (BCVA). METHODS: This was a prospective, interventional case series study of 53 eyes of 53 patients that underwent ERM removal with internal limiting membrane (ILM) peeling. Examinations were performed before, 1, 2, 3, 6, 9, 12, 24, 36, 48, and 60 months after the surgery. The average macular thicknesses in nine sectors outlined by the Early Treatment Diabetic Retinopathy Study were measured by spectral-domain optical coherence tomography. The final macular thicknesses of nine sectors of the 35 patients were compared with that of the normal fellow eyes. RESULTS: All patients were followed for 36 months, and 21 patients were followed for 48 months. The thicknesses of all sectors progressively decreased for 48 months. The macula at 48 months was thinner than at 36 months (P < 0.0001-0.037) in all sectors. The final central and nasal sectors were significantly thicker than that of the fellow eyes. The final inner and outer temporal sectors were significantly thinner compared with the fellow eyes. There was no significant difference in the other sectors. The pre- and postoperative central macular thickness was significantly correlated with the postoperative BCVA at each examination. CONCLUSIONS: A progressive thinning of the macula occurs with regional differences for at least 48 months. The temporal sector becomes thinner than the normal thickness. PMID- 26540660 TI - Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation. AB - PURPOSE: Cystinosis is caused by a deficiency in the lysosomal cystine transporter, cystinosin (CTNS gene), resulting in cystine crystal accumulation in tissues. In eyes, crystals accumulate in the cornea causing photophobia and eventually blindness. Hematopoietic stem progenitor cells (HSPCs) rescue the kidney in a mouse model of cystinosis. We investigated the potential for HSPC transplantation to treat corneal defects in cystinosis. METHODS: We isolated HSPCs from transgenic DsRed mice and systemically transplanted irradiated Ctns-/- mice. A year posttransplantation, we investigated the fate and function of HSPCs by in vivo confocal and fluorescence microscopy (IVCM), quantitative RT-PCR (RT qPCR), mass spectrometry, histology, and by measuring the IOP. To determine the mechanism by which HSPCs may rescue disease cells, we transplanted Ctns-/- mice with Ctns-/- DsRed HSPCs virally transduced to express functional CTNS-eGFP fusion protein. RESULTS: We found that a single systemic transplantation of wild type HSPCs prevented ocular pathology in the Ctns-/- mice. Engraftment-derived HSPCs were detected within the cornea, and also in the sclera, ciliary body, retina, choroid, and lens. Transplantation of HSPC led to substantial decreases in corneal cystine crystals, restoration of normal corneal thickness, and lowered IOP in mice with high levels of donor-derived cell engraftment. Finally, we found that HSPC-derived progeny differentiated into macrophages, which displayed tunneling nanotubes capable of transferring cystinosin-bearing lysosomes to diseased cells. CONCLUSIONS: To our knowledge, this is the first demonstration that HSPCs can rescue hereditary corneal defects, and supports a new potential therapeutic strategy for treating ocular pathologies. PMID- 26540663 TI - Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure. AB - BACKGROUND: In patients with advanced refractory heart failure (HF) cardiac transplantation (HTX), conservative medical management and the implantation of a ventricular assist device (VAD) represent valuable options. The determination of the best therapeutic destination strategy for the individual patient remains a challenge. The aim of this study was to assess the clinical outcome in advanced refractory HF patients either managed conservatively receiving optimal contemporary medical therapy ('conservative'), or who who underwent pulsatile flow VAD ('pVAD') or continuous-flow VAD ('contVAD') implantation. MATERIALS AND METHODS: A total of 118 patients with INTERMACS profile >1 at baseline, who died, or fully completed a 24-month follow-up free from HTX were included into this retrospective analysis. All-cause mortality at 24 months was assessed and compared between the three groups. RESULTS: Fifty (42%) patients were managed conservatively, 25 (21%) received a pVAD and 43 (36%) a contVAD. NT-proBNP values were comparable between the three groups (median 4402 (IQR 2730-13390) pg/mL, 3580 (1602-6312) pg/mL and 3693 (2679-8065) pg/mL, P = 0.256). Mean survival was 18.6 (95% CI 16.2-21.0) months for patients managed conservatively, 7.0 (3.9 10.0) for pVAD and 20.5 (18.2-22.8) for contVAD (overall log-rank test P < 0.001). Conservatively managed patients spent a mean of 22.4 (95% CI 22.1-22.8), pVAD 17.7 (15.4-20.1) and contVAD 21.6 (21.2-22.1) months out of hospital (conservative vs. pVAD P < 0.001; conservative vs. contVAD P = 0.015; pVAD vs. contVAD P < 0.001). CONCLUSIONS: In accordance with the literature, contVAD resulted in a significantly better clinical outcome than pVAD implantation. However, conservative management with current optimal medical therapy appears to remain a valuable option for patients with advanced HF. PMID- 26540664 TI - Systematic investigation of non-Boussinesq effects in variable-density groundwater flow simulations. AB - The validity of three mathematical models describing variable-density groundwater flow is systematically evaluated: (i) a model which invokes the Oberbeck Boussinesq approximation (OB approximation), (ii) a model of intermediate complexity (NOB1) and (iii) a model which solves the full set of equations (NOB2). The NOB1 and NOB2 descriptions have been added to the HydroGeoSphere (HGS) model, which originally contained an implementation of the OB description. We define the Boussinesq parameter epsilonrho=betaomega Deltaomega where betaomega is the solutal expansivity and Deltaomega is the characteristic difference in solute mass fraction. The Boussinesq parameter epsilonrho is used to systematically investigate three flow scenarios covering a range of free and mixed convection problems: 1) the low Rayleigh number Elder problem (Van Reeuwijk et al., 2009), 2) a convective fingering problem (Xie et al., 2011) and 3) a mixed convective problem (Schincariol et al., 1994). Results indicate that small density differences (epsilonrho<= 0.05) produce no apparent changes in the total solute mass in the system, plume penetration depth, center of mass and mass flux independent of the mathematical model used. Deviations between OB, NOB1 and NOB2 occur for large density differences (epsilonrho>0.12), where lower description levels will underestimate the vertical plume position and overestimate mass flux. Based on the cases considered here, we suggest the following guidelines for saline convection: the OB approximation is valid for cases with epsilonrho<0.05, and the full NOB set of equations needs to be used for cases with epsilonrho>0.10. Whether NOB effects are important in the intermediate region differ from case to case. PMID- 26540662 TI - Emergence of Pathogenicity in Lagoviruses: Evolution from Pre-existing Nonpathogenic Strains or through a Species Jump? PMID- 26540665 TI - Breath Activity Monitoring With Wearable UWB Radars: Measurement and Analysis of the Pulses Reflected by the Human Body. AB - OBJECTIVE: Measurements of ultrawideband (UWB) pulses reflected by the human body are conducted to evidence the differences in the received signal time behaviors due to respiration phases, and to experimentally verify previously obtained numerical results on the body's organs responsible for pulse reflection. METHODS: Two experimental setups are used. The first one is based on a commercially available impulse radar system integrated on a single chip, while the second one implements an indirect time-domain reflectometry technique using a vector network analyzer controlled by a LabVIEW virtual instrument running on a laptop. RESULTS: When the UWB source is placed close to the human body, a small reflection due to the lung boundaries is present in the received pulse well distanced in time from the reflection due to the air-skin interface; this reflection proved to be linked to the different respiration phases. CONCLUSIONS: The changes in the reflected pulse could be used to detect, through wearable radar systems, lung movements associated with the breath activity. SIGNIFICANCE: The development of a wearable radar system is of great importance because it allows the breath activity sensing without interfering with the subject daily activities. PMID- 26540667 TI - Monitoring of Postoperative Bone Healing Using Smart Trauma-Fixation Device With Integrated Self-Powered Piezo-Floating-Gate Sensors. AB - OBJECTIVE: Achieving better surgical outcomes in cases of traumatic bone fractures requires postoperative monitoring of changes in the growth and mechanical properties of the tissue and bones during the healing process. While current in-vivo imaging techniques can provide a snapshot of the extent of bone growth, it is unable to provide a history of the healing process, which is important if any corrective surgery is required. Monitoring the time evolution of in-vivo mechanical loads using existing technology is a challenge due to the need for continuous power while maintaining patient mobility and comfort. METHODS: This paper investigates the feasibility of self-powered monitoring of the bone healing process using our previously reported piezo-floating-gate (PFG) sensors. The sensors are directly integrated with a fixation device and operate by harvesting energy from microscale strain variations in the fixation structure. RESULTS: We show that the sensors can record and store the statistics of the strain evolution during the healing process for offline retrieval and analysis. Additionally, we present measurement results using a biomechanical phantom comprising of a femur fracture fixation plate; bone healing is emulated by inserting different materials, with gradually increasing elastic moduli, inside a fracture gap. CONCLUSION: The PFG sensor can effectively sense, compute, and record continuously evolving statistics of mechanical loading over a typical healing period of a bone, and the statistics could be used to differentiate between different bone-healing conditions. SIGNIFICANCE: The proposed sensor presents a reliable objective technique to assess bone-healing progress and help decide on the removal time of the fixation device. PMID- 26540668 TI - A Dataset for Breast Cancer Histopathological Image Classification. AB - Today, medical image analysis papers require solid experiments to prove the usefulness of proposed methods. However, experiments are often performed on data selected by the researchers, which may come from different institutions, scanners, and populations. Different evaluation measures may be used, making it difficult to compare the methods. In this paper, we introduce a dataset of 7909 breast cancer histopathology images acquired on 82 patients, which is now publicly available from http://web.inf.ufpr.br/vri/breast-cancer-database. The dataset includes both benign and malignant images. The task associated with this dataset is the automated classification of these images in two classes, which would be a valuable computer-aided diagnosis tool for the clinician. In order to assess the difficulty of this task, we show some preliminary results obtained with state-of-the-art image classification systems. The accuracy ranges from 80% to 85%, showing room for improvement is left. By providing this dataset and a standardized evaluation protocol to the scientific community, we hope to gather researchers in both the medical and the machine learning field to advance toward this clinical application. PMID- 26540666 TI - Inherent Structure-Based Multiview Learning With Multitemplate Feature Representation for Alzheimer's Disease Diagnosis. AB - Multitemplate-based brain morphometric pattern analysis using magnetic resonance imaging has been recently proposed for automatic diagnosis of Alzheimer's disease (AD) and its prodromal stage (i.e., mild cognitive impairment or MCI). In such methods, multiview morphological patterns generated from multiple templates are used as feature representation for brain images. However, existing multitemplate based methods often simply assume that each class is represented by a specific type of data distribution (i.e., a single cluster), while in reality, the underlying data distribution is actually not preknown. In this paper, we propose an inherent structure-based multiview leaning method using multiple templates for AD/MCI classification. Specifically, we first extract multiview feature representations for subjects using multiple selected templates and then cluster subjects within a specific class into several subclasses (i.e., clusters) in each view space. Then, we encode those subclasses with unique codes by considering both their original class information and their own distribution information, followed by a multitask feature selection model. Finally, we learn an ensemble of view-specific support vector machine classifiers based on their, respectively, selected features in each view and fuse their results to draw the final decision. Experimental results on the Alzheimer's Disease Neuroimaging Initiative database demonstrate that our method achieves promising results for AD/MCI classification, compared to the state-of-the-art multitemplate-based methods. PMID- 26540669 TI - A comparison of small-area hospitalisation rates, estimated morbidity and hospital access. AB - Published data on hospitalisation rates tend to reveal marked spatial variations within a city or region. Such variations may simply reflect corresponding variations in need at the small-area level. However, they might also be a consequence of poorer accessibility to medical facilities for certain communities within the region. To help answer this question it is important to compare these variable hospitalisation rates with small-area estimates of need. This paper first maps hospitalisation rates at the small-area level across the region of Yorkshire in the UK to show the spatial variations present. Then the Health Survey of England is used to explore the characteristics of persons with heart disease, using chi-square and logistic regression analysis. Using the most significant variables from this analysis the authors build a spatial microsimulation model of morbidity for heart disease for the Yorkshire region. We then compare these estimates of need with the patterns of hospitalisation rates seen across the region. PMID- 26540671 TI - Effect of Regulatory Requirement for Patient-Specific Prescriptions for Off-Label Medications on the Use of Intravitreal Bevacizumab. AB - IMPORTANCE: Requirements regulating pharmaceutical prescriptions can affect physicians' choice of therapy in a clinical setting. OBJECTIVE: To evaluate the change in bevacizumab use after the regulatory requirement for patient-specific prescriptions (PSPs) for off-label medications in Ohio. DESIGN, SETTING, AND PARTICIPANTS: This study retrospectively reviewed the aggregate data from the billing records of patients receiving 1.25-mg injections of bevacizumab, 0.3- or 0.5-mg injections of ranibizumab, or 2.0-mg injections of aflibercept for age related macular degeneration or diabetic macular edema in a 9-member retinal specialty private practice. The review assessed 4488 intravitreal injections in the 3-month period before (May 1 to July 30, 2012) and 5253 injections in the 3 month period after (May 1 to July 30, 2013) the Ohio Board of Pharmacy's requirement of PSPs for bevacizumab. Relative proportions of the drugs used for intravitreal injections were calculated and frequencies were compared. A Likert scale survey was conducted among the 9 physicians to identify reasons for their change in prescription of bevacizumab. The survey inquired about (1) the burden of PSPs, (2) concern about differences in efficacy, and (3) concern about differences in safety. MAIN OUTCOMES AND MEASURES: Difference in drug use before and after the PSP requirement for bevacizumab and the physicians' reasons for change in their drug use. RESULTS: Bevacizumab use decreased from 2752 of 4488 pre-PSP injections (61.3%) to 1503 of 5253 post-PSP injections (28.6%), a change of -32.7% (95% CI, -34.6% to -30.8%; P < .001). Use of 0.5-mg ranibizumab injections increased from 1122 of 4488 pre-PSP injections (25.0%) to 1838 of 5253 post-PSP injections (35.0%), a change of 10.0% (95% CI, 8.2% to 11.8%; P < .001). Use of 0.3-mg ranibizumab injections increased from 0 of 4488 (before US Food and Drug Administration approval) to 429 of 5253 post-PSP injections (8.2%), a change of 8.2% (95% CI, 7.4% to 8.9%; P < .001). Use of aflibercept injections increased from 614 of 4488 pre-PSP injections (13.7%) to 1483 of 5253 post-PSP injections (28.2%), a change of 14.6% (95% CI, 13.0%-16.1%; P < .001). In the survey of the 9 physicians concerning their reasons for decreased use of bevacizumab, 7 (78%) strongly agreed and 1 (11%) agreed that the burden of PSPs changed their choice of drug used for injection. CONCLUSIONS AND RELEVANCE: Use of bevacizumab was reduced by 32.7% 1 year after the regulatory requirement for PSPs for compounded (repackaged) medications. This change seemed to have more association with the requirement for PSPs than with a known change in efficacy or safety concerns. Although this study was based on a single US practice, regulation of repackaged medication for safety concerns should also consider the evaluation of treatment burden, cost, and adherence. PMID- 26540673 TI - Discriminative Unsupervised Feature Learning with Exemplar Convolutional Neural Networks. AB - Deep convolutional networks have proven to be very successful in learning task specific features that allow for unprecedented performance on various computer vision tasks. Training of such networks follows mostly the supervised learning paradigm, where sufficiently many input-output pairs are required for training. Acquisition of large training sets is one of the key challenges, when approaching a new task. In this paper, we aim for generic feature learning and present an approach for training a convolutional network using only unlabeled data. To this end, we train the network to discriminate between a set of surrogate classes. Each surrogate class is formed by applying a variety of transformations to a randomly sampled 'seed' image patch. In contrast to supervised network training, the resulting feature representation is not class specific. It rather provides robustness to the transformations that have been applied during training. This generic feature representation allows for classification results that outperform the state of the art for unsupervised learning on several popular datasets (STL 10, CIFAR-10, Caltech-101, Caltech-256). While features learned with our approach cannot compete with class specific features from supervised training on a classification task, we show that they are advantageous on geometric matching problems, where they also outperform the SIFT descriptor. PMID- 26540670 TI - Multifunctional MRI/PET Nanobeacons Derived from the in Situ Self-Assembly of Translational Polymers and Clinical Cargo through Coalescent Intermolecular Forces. AB - Novel multifunctional platforms are needed for oncology in order to assist physicians during surgery and chemotherapy. In the present study, we show that polymeric nanobeacons, consisting of the glucose-based polymer dextran, can be used to guide surgery and improve drug delivery. For imaging, the nanobeacons stably retained the positron emitter 89-zirconium and the MRI contrast agent gadolinium, without the need of a chelator. In addition to using them for PET imaging, the (89)Zr-nanobeacons guided the surgical resection of sentinel lymph nodes, utilizing their inherent Cerenkov luminescence. Through weak electrostatic interactions, the nanoparticles carried combinations of chemotherapeutics for the simultaneous inhibition of oncogenic pathways, resulting in enhanced tumor regression. The nanobeacons also allowed monitoring of drug release via MRI, through the quenching of the gadolinium signal by the coloaded drug, making them a new multifunctional theranostic nanotechnology platform for the clinic. PMID- 26540672 TI - Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway. AB - OBJECTIVE: Orofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively. DESIGN: Specifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested. RESULTS: A decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes=0.53; 95% confidence interval [C.I.]=0.32-0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association. CONCLUSION: Overall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds. PMID- 26540674 TI - Principal Curves on Riemannian Manifolds. AB - Euclidean statistics are often generalized to Riemannian manifolds by replacing straight-line interpolations with geodesic ones. While these Riemannian models are familiar-looking, they are restricted by the inflexibility of geodesics, and they rely on constructions which are optimal only in Euclidean domains. We consider extensions of Principal Component Analysis (PCA) to Riemannian manifolds. Classic Riemannian approaches seek a geodesic curve passing through the mean that optimizes a criteria of interest. The requirements that the solution both is geodesic and must pass through the mean tend to imply that the methods only work well when the manifold is mostly flat within the support of the generating distribution. We argue that instead of generalizing linear Euclidean models, it is more fruitful to generalize non-linear Euclidean models. Specifically, we extend the classic Principal Curves from Hastie & Stuetzle to data residing on a complete Riemannian manifold. We show that for elliptical distributions in the tangent of spaces of constant curvature, the standard principal geodesic is a principal curve. The proposed model is simple to compute and avoids many of the pitfalls of traditional geodesic approaches. We empirically demonstrate the effectiveness of the Riemannian principal curves on several manifolds and datasets. PMID- 26540675 TI - Probabilistic Social Behavior Analysis by Exploring Body Motion-Based Patterns. AB - Understanding human behavior through nonverbal-based features, is interesting in several applications such as surveillance, ambient assisted living and human robot interaction. In this article in order to analyze human behaviors in social context, we propose a new approach which explores interrelations between body part motions in scenarios with people doing a conversation. The novelty of this method is that we analyze body motion-based features in frequency domain to estimate different human social patterns: Interpersonal Behaviors (IBs) and a Social Role (SR). To analyze the dynamics and interrelations of people's body motions, a human movement descriptor is used to extract discriminative features, and a multi-layer Dynamic Bayesian Network (DBN) technique is proposed to model the existent dependencies. Laban Movement Analysis (LMA) is a well-known human movement descriptor, which provides efficient mid-level information of human body motions. The mid-level information is useful to extract the complex interdependencies. The DBN technique is tested in different scenarios to model the mentioned complex dependencies. The study is applied for obtaining four IBs (Interest, Indicator, Empathy and Emphasis) to estimate one SR (Leading).The obtained results give a good indication of the capabilities of the proposed approach for people interaction analysis with potential applications in human robot interaction. PMID- 26540676 TI - Real-Time Lexicon-Free Scene Text Localization and Recognition. AB - An end-to-end real-time text localization and recognition method is presented. Its real-time performance is achieved by posing the character detection and segmentation problem as an efficient sequential selection from the set of Extremal Regions. The ER detector is robust against blur, low contrast and illumination, color and texture variation. In the first stage, the probability of each ER being a character is estimated using features calculated by a novel algorithm in constant time and only ERs with locally maximal probability are selected for the second stage, where the classification accuracy is improved using computationally more expensive features. A highly efficient clustering algorithm then groups ERs into text lines and an OCR classifier trained on synthetic fonts is exploited to label character regions. The most probable character sequence is selected in the last stage when the context of each character is known. The method was evaluated on three public datasets. On the ICDAR 2013 dataset the method achieves state-of-the-art results in text localization; on the more challenging SVT dataset, the proposed method significantly outperforms the state-of-the-art methods and demonstrates that the proposed pipeline can incorporate additional prior knowledge about the detected text. The proposed method was exploited as the baseline in the ICDAR 2015 Robust Reading competition, where it compares favourably to the state-of-the art. PMID- 26540677 TI - SALSA: A Novel Dataset for Multimodal Group Behavior Analysis. AB - Studying free-standing conversational groups (FCGs) in unstructured social settings (e.g., cocktail party ) is gratifying due to the wealth of information available at the group (mining social networks) and individual (recognizing native behavioral and personality traits) levels. However, analyzing social scenes involving FCGs is also highly challenging due to the difficulty in extracting behavioral cues such as target locations, their speaking activity and head/body pose due to crowdedness and presence of extreme occlusions. To this end, we propose SALSA, a novel dataset facilitating multimodal and Synergetic sociAL Scene Analysis, and make two main contributions to research on automated social interaction analysis: (1) SALSA records social interactions among 18 participants in a natural, indoor environment for over 60 minutes, under the poster presentation and cocktail party contexts presenting difficulties in the form of low-resolution images, lighting variations, numerous occlusions, reverberations and interfering sound sources; (2) To alleviate these problems we facilitate multimodal analysis by recording the social interplay using four static surveillance cameras and sociometric badges worn by each participant, comprising the microphone, accelerometer, bluetooth and infrared sensors. In addition to raw data, we also provide annotations concerning individuals' personality as well as their position, head, body orientation and F-formation information over the entire event duration. Through extensive experiments with state-of-the-art approaches, we show (a) the limitations of current methods and (b) how the recorded multiple cues synergetically aid automatic analysis of social interactions. SALSA is available at http://tev.fbk.eu/salsa. PMID- 26540679 TI - An Efficient and Configurable Preprocessing Algorithm to Improve Stability Analysis. AB - The Allan variance (AVAR) is widely used to measure the stability of experimental time series. Specifically, AVAR is commonly used in space applications such as monitoring the clocks of the global navigation satellite systems (GNSSs). In these applications, the experimental data present some peculiar aspects which are not generally encountered when the measurements are carried out in a laboratory. Space clocks' data can in fact present outliers, jumps, and missing values, which corrupt the clock characterization. Therefore, an efficient preprocessing is fundamental to ensure a proper data analysis and improve the stability estimation performed with the AVAR or other similar variances. In this work, we propose a preprocessing algorithm and its implementation in a robust software code (in MATLAB language) able to deal with time series of experimental data affected by nonstationarities and missing data; our method is properly detecting and removing anomalous behaviors, hence making the subsequent stability analysis more reliable. PMID- 26540678 TI - Superpixel-Based Segmentation for 3D Prostate MR Images. AB - This paper proposes a method for segmenting the prostate on magnetic resonance (MR) images. A superpixel-based 3D graph cut algorithm is proposed to obtain the prostate surface. Instead of pixels, superpixels are considered as the basic processing units to construct a 3D superpixel-based graph. The superpixels are labeled as the prostate or background by minimizing an energy function using graph cut based on the 3D superpixel-based graph. To construct the energy function, we proposed a superpixel-based shape data term, an appearance data term, and two superpixel-based smoothness terms. The proposed superpixel-based terms provide the effectiveness and robustness for the segmentation of the prostate. The segmentation result of graph cuts is used as an initialization of a 3D active contour model to overcome the drawback of the graph cut. The result of 3D active contour model is then used to update the shape model and appearance model of the graph cut. Iterations of the 3D graph cut and 3D active contour model have the ability to jump out of local minima and obtain a smooth prostate surface. On our 43 MR volumes, the proposed method yields a mean Dice ratio of 89.3 +/-1.9%. On PROMISE12 test data set, our method was ranked at the second place; the mean Dice ratio and standard deviation is 87.0+/-3.2%. The experimental results show that the proposed method outperforms several state-of the-art prostate MRI segmentation methods. PMID- 26540680 TI - A Low Frequency Broadband Flextensional Ultrasonic Transducer Array. AB - In this paper, we propose the design and the fabrication of a multicell, piezoelectrically actuated, flextensional transducer array structure, characterized by a low mechanical impedance, thus allowing wideband and high sensitivity immersion operation in the low ultrasonic frequency range. The transducer structure, consisting of a plurality of circular elementary cells orderly arranged according to a periodic hexagonal tiling, features a high flexibility in the definition of the active area shape and size. We investigate, by finite element modeling (FEM), the influence of different piezoelectric and elastic materials for the flexural plate, for the plate support and for the backing, on the transducer electroacoustic behavior. We carry out the dimensioning of the transducer components and cell layout, in terms of materials and geometry, respectively, by aiming at a circular active area of 80-mm diameter and broadband operation in the 30-100-kHz frequency range in immersion. PZT-5H ceramic disks and a calibrated thickness stainless steel plate are chosen for the vibrating structure, and FR-4 laminates and a brass plate, respectively, for the plate support and the backing. The diameter of the individual cells is set to 6 mm resulting in 121 cells describing a quasi-circular area, and the total thickness of the transducer is less than 10 mm. We report on the fabrication process flow for the accurate assembly of the transducer, based, respectively, on epoxy resin and wire bonding for the mechanical and electrical interconnection of the individual parts. The results of the electrical impedance and transmit pressure field characterization are finally reported and discussed. PMID- 26540681 TI - Application of the Allan Variance to Time Series Analysis in Astrometry and Geodesy: A Review. AB - The Allan variance (AVAR) was introduced 50 years ago as a statistical tool for assessing the frequency standards deviations. For the past decades, AVAR has increasingly been used in geodesy and astrometry to assess the noise characteristics in geodetic and astrometric time series. A specific feature of astrometric and geodetic measurements, as compared with clock measurements, is that they are generally associated with uncertainties; thus, an appropriate weighting should be applied during data analysis. In addition, some physically connected scalar time series naturally form series of multidimensional vectors. For example, three station coordinates time series X, Y, and Z can be combined to analyze 3-D station position variations. The classical AVAR is not intended for processing unevenly weighted and/or multidimensional data. Therefore, AVAR modifications, namely weighted AVAR (WAVAR), multidimensional AVAR (MAVAR), and weighted multidimensional AVAR (WMAVAR), were introduced to overcome these deficiencies. In this paper, a brief review is given of the experience of using AVAR and its modifications in processing astrogeodetic time series. PMID- 26540682 TI - PVDF Multielement Lamb Wave Sensor for Structural Health Monitoring. AB - The characteristics of Lamb waves, which are multimodal and dispersive, provide both challenges and opportunities for structural health monitoring (SHM). Methods for nondestructive testing with Lamb waves are well established. For example, mode content can be determined by moving a sensor to different positions and then transforming the spatial-temporal data into the wavenumber-frequency domain. This mode content information is very useful because at every frequency each mode has a unique wavestructure, which is largely responsible for its sensitivity to material damage. Furthermore, mode conversion occurs when the waves interact with damage, making mode content an excellent damage detection feature. However, in SHM, the transducers are typically at fixed locations and are immovable. Here, an affixed polyvinylidene fluoride (PVDF) multielement sensor is shown to provide these same capabilities. The PVDF sensor is bonded directly to the waveguide surface, conforms to curved surfaces, has low mass, low profile, low cost, and minimal influence on passing Lamb waves. While the mode receivability is dictated by the sensor being located on the surface of the waveguide, both symmetric and antisymmetric modes can be detected and group velocities measured. PMID- 26540683 TI - A Prototype PZT Matrix Transducer With Low-Power Integrated Receive ASIC for 3-D Transesophageal Echocardiography. AB - This paper presents the design, fabrication, and experimental evaluation of a prototype lead zirconium titanate (PZT) matrix transducer with an integrated receive ASIC, as a proof of concept for a miniature three-dimensional (3-D) transesophageal echocardiography (TEE) probe. It consists of an array of 9 *12 piezoelectric elements mounted on the ASIC via an integration scheme that involves direct electrical connections between a bond-pad array on the ASIC and the transducer elements. The ASIC addresses the critical challenge of reducing cable count, and includes front-end amplifiers with adjustable gains and micro beamformer circuits that locally process and combine echo signals received by the elements of each 3 *3 subarray. Thus, an order-of-magnitude reduction in the number of receive channels is achieved. Dedicated circuit techniques are employed to meet the strict space and power constraints of TEE probes. The ASIC has been fabricated in a standard 0.18-MUm CMOS process and consumes only 0.44 mW/channel. The prototype has been acoustically characterized in a water tank. The ASIC allows the array to be presteered across +/-37 degrees while achieving an overall dynamic range of 77 dB. Both the measured characteristics of the individual transducer elements and the performance of the ASIC are in good agreement with expectations, demonstrating the effectiveness of the proposed techniques. PMID- 26540685 TI - Hyperspectral Super-Resolution of Locally Low Rank Images From Complementary Multisource Data. AB - Remote sensing hyperspectral images (HSIs) are quite often low rank, in the sense that the data belong to a low dimensional subspace/manifold. This has been recently exploited for the fusion of low spatial resolution HSI with high spatial resolution multispectral images in order to obtain super-resolution HSI. Most approaches adopt an unmixing or a matrix factorization perspective. The derived methods have led to state-of-the-art results when the spectral information lies in a low-dimensional subspace/manifold. However, if the subspace/manifold dimensionality spanned by the complete data set is large, i.e., larger than the number of multispectral bands, the performance of these methods mainly decreases because the underlying sparse regression problem is severely ill-posed. In this paper, we propose a local approach to cope with this difficulty. Fundamentally, we exploit the fact that real world HSIs are locally low rank, that is, pixels acquired from a given spatial neighborhood span a very low-dimensional subspace/manifold, i.e., lower or equal than the number of multispectral bands. Thus, we propose to partition the image into patches and solve the data fusion problem independently for each patch. This way, in each patch the subspace/manifold dimensionality is low enough, such that the problem is not ill posed anymore. We propose two alternative approaches to define the hyperspectral super-resolution through local dictionary learning using endmember induction algorithms. We also explore two alternatives to define the local regions, using sliding windows and binary partition trees. The effectiveness of the proposed approaches is illustrated with synthetic and semi real data. PMID- 26540684 TI - An Automatic 3D Facial Landmarking Algorithm Using 2D Gabor Wavelets. AB - In this paper, we present a novel approach to automatic 3D facial landmarking using 2D Gabor wavelets. Our algorithm considers the face to be a surface and uses map projections to derive 2D features from raw data. Extracted features include texture, relief map, and transformations thereof. We extend an established 2D landmarking method for simultaneous evaluation of these data. The method is validated by performing landmarking experiments on two data sets using 21 landmarks and compared with an active shape model implementation. On average, landmarking error for our method was 1.9 mm, whereas the active shape model resulted in an average landmarking error of 2.3 mm. A second study investigating facial shape heritability in related individuals concludes that automatic landmarking is on par with manual landmarking for some landmarks. Our algorithm can be trained in 30 min to automatically landmark 3D facial data sets of any size, and allows for fast and robust landmarking of 3D faces. PMID- 26540686 TI - Multimodal Task-Driven Dictionary Learning for Image Classification. AB - Dictionary learning algorithms have been successfully used for both reconstructive and discriminative tasks, where an input signal is represented with a sparse linear combination of dictionary atoms. While these methods are mostly developed for single-modality scenarios, recent studies have demonstrated the advantages of feature-level fusion based on the joint sparse representation of the multimodal inputs. In this paper, we propose a multimodal task-driven dictionary learning algorithm under the joint sparsity constraint (prior) to enforce collaborations among multiple homogeneous/heterogeneous sources of information. In this task-driven formulation, the multimodal dictionaries are learned simultaneously with their corresponding classifiers. The resulting multimodal dictionaries can generate discriminative latent features (sparse codes) from the data that are optimized for a given task such as binary or multiclass classification. Moreover, we present an extension of the proposed formulation using a mixed joint and independent sparsity prior, which facilitates more flexible fusion of the modalities at feature level. The efficacy of the proposed algorithms for multimodal classification is illustrated on four different applications--multimodal face recognition, multi-view face recognition, multi-view action recognition, and multimodal biometric recognition. It is also shown that, compared with the counterpart reconstructive-based dictionary learning algorithms, the task-driven formulations are more computationally efficient in the sense that they can be equipped with more compact dictionaries and still achieve superior performance. PMID- 26540687 TI - Tasking on Natural Statistics of Infrared Images. AB - Natural scene statistics (NSSs) provide powerful, perceptually relevant tools that have been successfully used for image quality analysis of visible light images. Since NSS capture statistical regularities that arise from the physical world, they are relevant to long wave infrared (LWIR) images, which differ from visible light images mainly by the wavelengths captured at the imaging sensors. We show that NSS models of bandpass LWIR images are similar to those of visible light images, but with different parameterizations. Using this difference, we exploit the power of NSS to successfully distinguish between LWIR images and visible light images. In addition, we study distortions unique to LWIR and find directional models useful for detecting the halo effect, simple bandpass models useful for detecting hotspots, and combinations of these models useful for measuring the degree of non-uniformity present in many LWIR images. For local distortion identification and measurement, we also describe a method for generating distortion maps using NSS features. To facilitate our evaluation, we analyze the NSS of LWIR images under pristine and distorted conditions, using four databases, each captured with a different IR camera. Predicting human performance for assessing distortion and quality in LWIR images is critical for task efficacy. We find that NSS features improve human targeting task performance prediction. Furthermore, we conducted a human study on the perceptual quality of noise-and blur-distorted LWIR images and create a new blind image quality predictor for IR images. PMID- 26540688 TI - Matching Images With Multiple Descriptors: An Unsupervised Approach for Locally Adaptive Descriptor Selection. AB - With the aim to improve the performance of feature matching, we present an unsupervised approach for adaptive description selection in the space of homographies. Inspired by the observation that the homographies of correct feature correspondences vary smoothly along the spatial domain, our approach stands on the unsupervised nature of feature matching, and can choose a good descriptor locally for matching each feature point, instead of using one global descriptor. To this end, the homography space serves as the domain for selecting various heterogeneous descriptors. Correspondences obtained by any descriptors are considered as points in the space, and their geometric coherence and spatial continuity are measured via computing the geodesic distances. In this way, mutual verification across different descriptors is allowed, and correct correspondences will be highlighted with a high degree of consistency short geodesic distances here. It follows that one-class SVM can be applied to identifying these correct correspondences, and achieves adaptive descriptor selection. The proposed approach is comprehensively compared with the state-of-the-art approaches, and evaluated on five benchmarks of image matching. The promising results manifest its effectiveness. PMID- 26540689 TI - Micro-Expression Recognition Using Color Spaces. AB - Micro-expressions are brief involuntary facial expressions that reveal genuine emotions and, thus, help detect lies. Because of their many promising applications, they have attracted the attention of researchers from various fields. Recent research reveals that two perceptual color spaces (CIELab and CIELuv) provide useful information for expression recognition. This paper is an extended version of our International Conference on Pattern Recognition paper, in which we propose a novel color space model, tensor independent color space (TICS), to help recognize micro-expressions. In this paper, we further show that CIELab and CIELuv are also helpful in recognizing micro-expressions, and we indicate why these three color spaces achieve better performance. A micro expression color video clip is treated as a fourth-order tensor, i.e., a four dimension array. The first two dimensions are the spatial information, the third is the temporal information, and the fourth is the color information. We transform the fourth dimension from RGB into TICS, in which the color components are as independent as possible. The combination of dynamic texture and independent color components achieves a higher accuracy than does that of RGB. In addition, we define a set of regions of interests (ROIs) based on the facial action coding system and calculated the dynamic texture histograms for each ROI. Experiments are conducted on two micro-expression databases, CASME and CASME 2, and the results show that the performances for TICS, CIELab, and CIELuv are better than those for RGB or gray. PMID- 26540690 TI - A Novel Motion Field Anchoring Paradigm for Highly Scalable Wavelet-Based Video Coding. AB - Existing video coders anchor motion fields at frames that are to be predicted. In this paper, we demonstrate how changing the anchoring of motion fields to reference frames has some important advantages over conventional anchoring. We work with piecewise-smooth motion fields, and use breakpoints to signal discontinuities at moving object boundaries. We show how discontinuity information can be used to resolve double mappings arising when motion is warped from reference to target frames. We present an analytical model that allows to determine weights for texture, motion, and breakpoints to guide the rate allocation for scalable encoding. Compared with the conventional way of anchoring motion fields, the proposed scheme requires fewer bits for the coding of motion; furthermore, the reconstructed video frames contain fewer ghosting artefacts. The experimental results show the superior performance compared with the traditional anchoring, and demonstrate the high scalability attributes of the proposed method. PMID- 26540691 TI - An Automated System for the Analysis of Newborns' Oral-Motor Behavior. AB - The assessment of oral-motor behavior (OMB) represents one the earliest noninvasive ways to evaluate newborns' well-being and neuromotor behavior. This work aimed at developing a new low-cost, easy-to-use and noninvasive system for a technology-aided assessment of newborns' OMB during bottle feeding. A SUcking MOnitoring Device (SUMOD) was designed and developed to be easily integrated on a typical feeding bottle. A software system was developed to automatically treat and analyze the acquired data: proper algorithms for a fully automatic segmentation and features extraction are proposed and implemented. A set of measures of motor control and coordination are introduced and implemented for the specific application to the OMB analysis. Experimental data were collected on two groups of newborns (healthy versus low birth weight) with the SUMOD in a clinical setting. PMID- 26540692 TI - Discovering Gene Regulatory Elements Using Coverage-Based Heuristics. AB - Data mining algorithms and sequencing methods (such as RNA-seq and ChIP-seq) are being combined to discover genomic regulatory motifs that relate to a variety of phenotypes. However, motif discovery algorithms often produce very long lists of putative transcription factor binding sites, hindering the discovery of phenotype related regulatory elements by making it difficult to select a manageable set of candidate motifs for experimental validation. To address this issue, the authors introduce the motif selection problem and provide coverage-based search heuristics for its solution. Analysis of 203 ChIP-seq experiments from the ENCyclopedia of DNA Elements project shows that our algorithms produce motifs that have high sensitivity and specificity and reveals new insights about the regulatory code of the human genome. The greedy algorithm performs the best, selecting a median of two motifs per ChIP-seq transcription factor group while achieving a median sensitivity of 77 percent. PMID- 26540693 TI - Time-Dependent Gene Network Modelling by Sequential Monte Carlo. AB - Most existing methods used for gene regulatory network modeling are dedicated to inference of steady state networks, which are prevalent over all time instants. However, gene interactions evolve over time. Information about the gene interactions in different stages of the life cycle of a cell or an organism is of high importance for biology. In the statistical graphical models literature, one can find a number of methods for studying steady-state network structures while the study of time varying networks is rather recent. A sequential Monte Carlo method, namely particle filtering (PF), provides a powerful tool for dynamic time series analysis. In this work, the PF technique is proposed for dynamic network inference and its potentials in time varying gene expression data tracking are demonstrated. The data used for validation are synthetic time series data available from the DREAM4 challenge, generated from known network topologies and obtained from transcriptional regulatory networks of S. cerevisiae. We model the gene interactions over the course of time with multivariate linear regressions where the parameters of the regressive process are changing over time. PMID- 26540694 TI - A Bio-Inspired AER Temporal Tri-Color Differentiator Pixel Array. AB - This article investigates the potential of a bio-inspired vision sensor with pixels that detect transients between three primary colors. The in-pixel color processing is inspired by the retinal color opponency that are found in mammalian retinas. Color transitions in a pixel are represented by voltage spikes, which are akin to a neuron's action potential. These spikes are conveyed off-chip by the Address Event Representation (AER) protocol. To achieve sensitivity to three different color spectra within the visual spectrum, each pixel has three stacked photodiodes at different depths in the silicon substrate. The sensor has been fabricated in the standard TSMC 90 nm CMOS technology. A post-processing method to decode events into color transitions has been proposed and implemented as a custom interface to display real-time color changes in the visual scene. Experimental results are provided. Color transitions can be detected at high speed (up to 2.7 kHz). The sensor has a dynamic range of 58 dB and a power consumption of 22.5 mW. This type of sensor can be of use in industrial, robotics, automotive and other applications where essential information is contained in transient emissions shifts within the visual spectrum. PMID- 26540695 TI - Cognitive Aging: Progress in Understanding and Opportunities for Action. PMID- 26540696 TI - Global Health and the U.S. Department of Defense: A Call for an Evidence Base. PMID- 26540698 TI - When, If Ever, Should Military Physicians Violate a Military Order to Give Medical Obligations Higher Priority? AB - Military care providers may face ethical conflicts when they must treat their own and enemy soldiers during combat and their resources are limited. Legally under the Geneva Convention, they are instructed to treat enemy soldiers equally, but in practice, providers still have some discretion. This article discusses this discretion and ethical frameworks and uncertainties that bear on these decisions. A case is presented in which this conflict arose. How the provider resolved this is reported. PMID- 26540697 TI - More Than "The Fighting Doctor": Brigadier General Bernard J. D. Irwin. PMID- 26540699 TI - Unmasking Burnout-Duality. PMID- 26540700 TI - Military Graduate Medical Education: Training the Military Health System into a High-Reliability Organization. PMID- 26540701 TI - Timing of Intimate Partner Violence in Relationship to Military Service Among Women Veterans. AB - Women U.S. military veterans report higher rates of lifetime intimate partner violence (IPV) compared with women who have never served in the military. However, we know little about the timing of IPV exposure relative to military service. To begin to understand the relationship between military service and IPV experience, we conducted surveys with 249 women military veterans seeking care at a Veterans Affairs medical center about experiences of physical, psychological, and sexual IPV before, during, and after military service. Additionally, we examined the association between deployment and IPV experience during and after military service. Findings indicated that women experienced IPV during each time period (before/during/after military service), with significant overlap of experiencing IPV during more than one time period and one-third (34.6%) experiencing IPV during all three time periods. Compared to those who were not deployed, women who had been deployed reported increased odds of experiencing psychological, but not physical or sexual, IPV during (but not after) military service. Implications of study findings for theory, research, and practice are discussed. PMID- 26540702 TI - A Retrospective Review of Screening Labs for Medical Clearance in a Military Population. AB - STUDY OBJECTIVE: We determine the incidence of clinically significant findings within mandatory screening studies during medical clearance of patients for psychiatric care. METHODS: This is a retrospective review of emergency department patients medically cleared for psychiatric care over 11 months. All patients evaluated for behavioral health-related issues are recorded on a daily report which was used to locate subjects. Laboratory studies were reviewed during that visit for the presence of abnormalities. If abnormalities were noted, the individual chart was reviewed. Our primary outcome was the incidence of clinically significant findings that warranted admission to a medical or surgical unit. RESULTS: 204 psychiatric patient reports were reviewed. 191 of these patients had screening studies performed. Seven patients were admitted to a nonpsychiatric unit. These admissions were all for elevated ethanol levels. These patients were admitted until their ethanol level decreased, and then transferred to a psychiatric facility. The total screening lab cost during this study period was $27,893. CONCLUSIONS: Routine screening has limited utility in this population and comes at significant cost. Further research should be directed to determine which patients may benefit from screening studies. PMID- 26540703 TI - The Cost of Deploying a Role 2 Medical Asset to Afghanistan. AB - OBJECTIVES: The costs of military assets, including medical resources, are necessary for military planners when determining their force make up. The monetary cost of operating a Role 3 unit, the most comprehensive medical asset in the combat theater, has been determined. The cost of operating a Role 2 (R2) facility-the less comprehensive but more common asset-has not been assessed. Here we estimate the cost of operating an R2 medical asset in Afghanistan. METHODS: Personnel costs were assessed by combining the U.S. Department of Defense estimate for personnel cost with the replacement costs for deployed staff. Manning was for a U.S. Marine Corps Shock Trauma Platoon and Forward Resuscitative Surgical System. RESULTS: It costs $2,956,873 a month to operate an R2 medical facility in Afghanistan. It also takes the place of a rifle platoon and disrupts the domestic military health care mission. CONCLUSION: The costs of operating an R2 medical facility are significant and should be considered when the medical benefits of an R2 are unclear. PMID- 26540704 TI - Airsickness: Etiology, Treatment, and Clinical Importance-A Review. AB - Airsickness is one of the forms of motion sickness, and is of significance in both commercial and military flight. Whereas commercial airline passengers may simply feel poorly, the effect of airsickness on military aircrew may lead to a decrement in performance and adversely affect the mission. This is of major importance in the case of flight safety, when a pilot who is incapacitated may endanger the aircraft. The problem is particularly evident in pilot training, because of the high incidence of airsickness at this stage in the pilot's career. The majority of aircrew undergo habituation to airsickness during their service, with a reduction in symptoms and improved function. Although airsickness is a wellknown problem in aviation, we were unable to locate a review of this topic in the literature. This review focuses on the characteristics, clinical evaluation, and treatment of airsickness. It also presents the experience of the Israeli flight academy, and our solution for Navy pilots who have to contend with the risk of seasickness before taking to the air. PMID- 26540705 TI - Occupational Medicine Model and Asthma Military Recruitment. AB - Medical evidence hints that asymptomatic recruits with a history of childhood asthma, quiescent since their 13th birthday, are still at risk for adverse changes in their clinical status following unfavorable environmental exposures during military deployment or combat. Asthmatic persons, claiming none or few symptoms, may still manifest airflow obstruction and display biomarkers of airway inflammation even when they are relatively asymptomatic and experience few if any respiratory complaints. The occupational medicine model offers a credible foundation for acknowledging the importance of personal susceptibility in the pathogenesis of military-associated asthma. It is appropriate to re-explore the current military standard for recruits with asymptomatic childhood asthma (>=12 months) not prescribed antiasthma medications. Raising the acceptance age for these recruits may be a consideration. Unfortunately, there is no effectual screening test that recognizes such susceptible soldiers at risk for future asthma attacks. Nevertheless, there is general support for evidence-based, scientifically valid medical screening that judges fitness for military service. Screening tests comprising asthma biomarkers and genetic indices may better verify vulnerable soldiers destined to suffer future asthma reactivation. PMID- 26540706 TI - Types, Subtypes, and Severity of Substantiated Child Neglect in U.S. Army Communities. AB - BACKGROUND: Neglect has been linked to short-term and long-term deleterious outcomes in children, but has received little attention in the research literature. OBJECTIVE: Identify types, subtypes, and severity of child neglect in a sample of substantiated cases at 4 U.S. Army installations. Describe demographic correlates of victims and offenders by type and subtype. PARTICIPANTS: Data were collected from archived clinical records. A stratified random sample of 100 substantiated child neglect case files were selected per site (N = 400). Data from a single child per case file were used. RESULTS: 5 types and 17 subtypes of neglect were represented, singly or in combination, with varying severity. Lack of Supervision was most common (n = 177, 35.3%), followed by Emotional Neglect (n = 159, 31.8%), Failure to Provide Physical Needs (n = 131, 26.2%), Moral-Legal Neglect (n = 20, 4%), and Educational Neglect (n = 13; 2.6%). Child neglect occurred mostly among young children and in young enlisted families. CONCLUSIONS: Current results highlight the need to focus on types, subtypes, and severity of neglect incidents that provide specific understanding of child risk to better inform policy. Further study should examine specific risk factors and their relationship to neglect types and severity outcomes. PMID- 26540707 TI - Active Duty Women's Perceptions of Breast-Feeding Support in the Military Setting. AB - BACKGROUND: The purpose of this study is to evaluate the current perceptions of breast-feeding support for active duty women serving in the U.S. Armed Forces. METHODS: An online survey based on the Workplace Breastfeeding Support Scale (WBSS) was used to collect data from active duty military mothers. Data were collected and analyzed using SPSS software to evaluate active duty women's perceptions of breast-feeding support in the military. RESULTS: 318 active duty women participated in the online survey. The average WBSS scores for active duty women was 50.20 (SD = 15.75). Comparing WBSS scores and branch of service, women in the Army had significantly lower WBSS scores (M = 45.85) then women in the Air Force (M = 53.96, p < 0.001). Enlisted women had significantly lower scores (M = 47.12) than officers (M = 54.62, p < 0.001). Also noted were significantly lower scores of active duty women who were Hispanic (M = 44.30) and women who had lower levels of education (M = 46.90, p = 0.006). CONCLUSIONS: The Department of Defense may be able to improve breast-feeding rates for all active duty mothers by implementing and adhering to lactation policies and focusing support efforts for enlisted women in all branches of service. PMID- 26540708 TI - Surveyed Enrollees in Veterans Affairs Health Care: How They Differ From Eligible Veterans Surveyed by BRFSS. AB - OBJECTIVES: We described differences in demographic and socioeconomic characteristics between Veterans enrolled in the Veterans Health Administration (VHA) and Veterans eligible to enroll for Veterans Affairs health care. Knowledge of these differences is important in planning better services for Veterans who enroll and in encouraging additional enrollment. METHODS: We compared characteristics of enrollees and eligible Veterans in 2012. To describe enrollees, we used aggregate data from administrative records and results from VHA's Survey of Veteran Enrollees' Health and Reliance Upon VA. To describe eligible Veterans, we analyzed individual-level data from the Behavioral Risk Factor Surveillance System. RESULTS: Elderly individuals are more heavily represented among enrollees than eligible Veterans, and elderly enrollees are less likely to describe their health as good to excellent. Enrollees are more than twice as likely as eligible Veterans to have annual household incomes below $16,000. Representation of minorities is roughly the same among enrollees as eligible Veterans. CONCLUSIONS: Our results are consistent with VHA as a safety net provider with respect to income, age, and disease burden. PMID- 26540709 TI - Evaluation of the Effectiveness of the 2008 Postsplenectomy Vaccination Joint Theater Trauma System Clinical Practice Guideline. AB - OBJECTIVES: Postsplenectomy vaccination (PSV) in an austere environment to minimize overwhelming postsplenectomy infection is challenging. We evaluated the clinical impact of a March 2008 clinical practice guideline (CPG) dictating immediate PSV at North American Treaty Organization Role 3 medical treatment facilities and subsequent complications. METHODS: Utilizing U.S. military medical databases, we characterized all U.S. patients with a splenic injury from November 2002 to January 2012 by their surgical management: laparotomy with splenectomy (LWS), laparotomy without splenectomy, or nonoperative management. Relevant data including demographics, vaccinations, and documented bacterial and fungal isolates were obtained. RESULTS: LWS comprised 63.6% of the 409 patients with a splenic injury from 2002 to 2012. The implementation of the PSV CPG improved overall vaccination compliance from 48.9% pre-PSV CPG to 86.9% post-PSV CPG (p < 0.01). It was found that 1.3% (2/159) of completely vaccinated LWS patients compared with 0% (0/101) of the incompletely vaccinated LWS patients had Streptococcus pneumoniae isolates in 391.0 and 251.4 follow-up years, respectively (p = 0.52). No Neisseria meningitidis or Haemophilus influenzae isolates were identified. CONCLUSIONS: PSV CPG implementation improved theater vaccination without increasing the incidence of encapsulated organisms. PMID- 26540710 TI - Impact of Arm Immersion Cooling During Ranger Training on Exertional Heat Illness and Treatment Costs. AB - Ranger training includes strenuous physical activities and despite heat mitigations strategies, numerous cases of serious exertional heat illness (EHI) occur. We developed an Arm Immersion Cooling (AIC) system that is not logistically burdensome and may be easily employed in training environments. PURPOSE: To examine the effect of AIC on EHI incidence, severity, and treatment costs during Ranger School. METHODS: The training program was standardized for physical exertion and heat stress factors throughout the study period. AIC was employed summer months of 2010-2012 (n = 3,930 Soldiers) and Control (CON; n = 6,650 Soldiers) data were obtained for summer months of 2007-2009. Descriptive characteristics of all EHI casualties were obtained, including hospitalization status (treated and released [Treat], evacuated [Evac] or admitted [Admit] to the hospital), which served as proxy indicator of illness/injury severity. Medical cost savings were calculated from hospital records. RESULTS: Incidence rates were not different (CON 4.06 vs. AIC 4.00/1,000 person-days). Treat increased during AIC (18.43 vs. 4.84/1,000 person-days) accompanied by marked but non-significant decreases in Evac and Admit rates. AIC use was associated with a medical cost savings of $1,719 per casualty. CONCLUSIONS: AIC implementation during strenuous physical training in summer months can reduce EHI severity and associated medical treatment costs. PMID- 26540711 TI - A 20-Year Epidemiological Review of Testis Cancer at a French Military Hospital. AB - OBJECTIVES: To determine if the epidemiology of testis cancer in military service has followed worldwide trends and if the end of conscription in 2000 in France marked an epidemiologic turn. METHODS: All of the patients who had an orchiectomy for a testis germ tumor from January 1990 to January 2011 were studied. The patients were divided into two groups: orchiectomy before 2000 and after 2000. RESULTS: 289 patients were included, with a mean age of 30.8. The mean age at diagnosis increased significantly as well as the proportion of stage 1 seminomas, whereas stage 1 nonseminomatous germ cell tumors (NSGCT) slightly decreased. For stage 1 seminomas, there was an increase in the surveillance (10% vs. 31%) and in the number of chemotherapies (19% vs. 22%); for stage 1 NSGCT, surveillance also increased (53% vs. 64%). The specific 5-year survival was 98.3%. CONCLUSIONS: We noted an increase in the number of stage 1 seminomas, the surveillance of located germ tumors, and an excellent survival rate. However, the population was younger with regard to national data, and the number of stage 1 NSGCT decreased in favor of advanced metastatic tumors. PMID- 26540712 TI - Control of Junctional Hemorrhage in a Consensus Swine Model With Hemostatic Gauze Products Following Minimal Training. AB - OBJECTIVE: Uncontrolled hemorrhage from junctional wounds that cannot be controlled by traditional tourniquets accounts for one in five preventable battlefield exsanguination deaths. Products for treating these wounds are costly and require special training. However, chemically treated gauze products are inexpensive, potentially effective, and require only minimal training. This study was designed to assess the efficacy of three hemostatic gauze products following brief training, using a consensus swine groin injury model. METHODS: After viewing a 15-minute PowerPoint presentation, without demonstration or practice, 24 U.S. Navy Corpsmen, most with little to no live tissue or hemostatic agent experience, applied one of three hemostatic agents: QuikClot Combat Gauze, Celox Trauma Gauze, or Hemcon ChitoGauze. Animals were resuscitated and monitored for 150 minutes to assess initial hemostasis, blood loss, rebleeding, and survival. Participants completed a survey before training and following testing. RESULTS: Products were similar in initial hemostasis, blood loss, and rebleeding. Twenty three swine survived (96%). Ease of use and perceived efficacy of training ratings were high. Comfort level with application improved following training. CONCLUSIONS: Hemostatic gauze can potentially be effective for treating junctional wounds following minimal training, which has important implications for corpsmen, self-aid/buddy-aid, civilian providers, and Tactical Combat Casualty Care guidelines. PMID- 26540713 TI - The Occupational Impact of Single-Level Cervical Disc Arthroplasty in an Active Duty Military Population. AB - INTRODUCTION: Degenerative cervical disease is a common condition affecting the general population. This process can have a detrimental effect on operational readiness and is a concern for military spine surgeons. Cervical disc arthroplasty (CDA) is a relatively new surgical treatment for cervical disease. OBJECTIVE: To evaluate the occupational impact of CDA used to treat single-level cervical disease in a high demand military population. METHODS: Case series of 34 patients with prospective follow-up who had undergone single-level CDA at our institution. RESULTS: Average follow-up was 21.4 months. Noncommissioned officer was the most common rank. C5-C6 was the most common operated level. 30/34 (88.2%) returned to active duty service. 4/34 (11.8%) went on to medical evaluation board for separation from active duty service. 28/30 (93.3%) returned to duty patients vs. 2/4 (50%) medical board patients reported relief with surgery. Average return to duty time was 8.5 weeks. All patients who returned to duty were able to maintain preoperative military occupational specialty. 8/30 (26.7%) were able to deploy postoperatively. CONCLUSION: CDA has the potential to allow return to high demand preoperative occupational activities in active duty military patients with single-level cervical disease. PMID- 26540714 TI - Virtual Anatomy-1900. PMID- 26540715 TI - Robust Adaptive Dynamic Programming of Two-Player Zero-Sum Games for Continuous Time Linear Systems. AB - In this brief, an online robust adaptive dynamic programming algorithm is proposed for two-player zero-sum games of continuous-time unknown linear systems with matched uncertainties, which are functions of system outputs and states of a completely unknown exosystem. The online algorithm is developed using the policy iteration (PI) scheme with only one iteration loop. A new analytical method is proposed for convergence proof of the PI scheme. The sufficient conditions are given to guarantee globally asymptotic stability and suboptimal property of the closed-loop system. Simulation studies are conducted to illustrate the effectiveness of the proposed method. PMID- 26540716 TI - Cooperative Strategy for Optimal Management of Smart Grids by Wavelet RNNs and Cloud Computing. AB - Advanced smart grids have several power sources that contribute with their own irregular dynamic to the power production, while load nodes have another dynamic. Several factors have to be considered when using the owned power sources for satisfying the demand, i.e., production rate, battery charge and status, variable cost of externally bought energy, and so on. The objective of this paper is to develop appropriate neural network architectures that automatically and continuously govern power production and dispatch, in order to maximize the overall benefit over a long time. Such a control will improve the fundamental work of a smart grid. For this, status data of several components have to be gathered, and then an estimate of future power production and demand is needed. Hence, the neural network-driven forecasts are apt in this paper for renewable nonprogrammable energy sources. Then, the produced energy as well as the stored one can be supplied to consumers inside a smart grid, by means of digital technology. Among the sought benefits, reduced costs and increasing reliability and transparency are paramount. PMID- 26540717 TI - LQR-Based Optimal Distributed Cooperative Design for Linear Discrete-Time Multiagent Systems. AB - In this paper, a novel linear quadratic regulator (LQR)-based optimal distributed cooperative design method is developed for synchronization control of general linear discrete-time multiagent systems on a fixed, directed graph. Sufficient conditions are derived for synchronization, which restrict the graph eigenvalues into a bounded circular region in the complex plane. The synchronizing speed issue is also considered, and it turns out that the synchronizing region reduces as the synchronizing speed becomes faster. To obtain more desirable synchronizing capacity, the weighting matrices are selected by sufficiently utilizing the guaranteed gain margin of the optimal regulators. Based on the developed LQR based cooperative design framework, an approximate dynamic programming technique is successfully introduced to overcome the (partially or completely) model-free cooperative design for linear multiagent systems. Finally, two numerical examples are given to illustrate the effectiveness of the proposed design methods. PMID- 26540718 TI - A Unified Framework for Representation-Based Subspace Clustering of Out-of-Sample and Large-Scale Data. AB - Under the framework of spectral clustering, the key of subspace clustering is building a similarity graph, which describes the neighborhood relations among data points. Some recent works build the graph using sparse, low-rank, and l2 norm-based representation, and have achieved the state-of-the-art performance. However, these methods have suffered from the following two limitations. First, the time complexities of these methods are at least proportional to the cube of the data size, which make those methods inefficient for solving the large-scale problems. Second, they cannot cope with the out-of-sample data that are not used to construct the similarity graph. To cluster each out-of-sample datum, the methods have to recalculate the similarity graph and the cluster membership of the whole data set. In this paper, we propose a unified framework that makes the representation-based subspace clustering algorithms feasible to cluster both the out-of-sample and the large-scale data. Under our framework, the large-scale problem is tackled by converting it as the out-of-sample problem in the manner of sampling, clustering, coding, and classifying. Furthermore, we give an estimation for the error bounds by treating each subspace as a point in a hyperspace. Extensive experimental results on various benchmark data sets show that our methods outperform several recently proposed scalable methods in clustering a large-scale data set. PMID- 26540719 TI - Adaptive Filter Design Using Type-2 Fuzzy Cerebellar Model Articulation Controller. AB - This paper aims to propose an efficient network and applies it as an adaptive filter for the signal processing problems. An adaptive filter is proposed using a novel interval type-2 fuzzy cerebellar model articulation controller (T2FCMAC). The T2FCMAC realizes an interval type-2 fuzzy logic system based on the structure of the CMAC. Due to the better ability of handling uncertainties, type-2 fuzzy sets can solve some complicated problems with outstanding effectiveness than type 1 fuzzy sets. In addition, the Lyapunov function is utilized to derive the conditions of the adaptive learning rates, so that the convergence of the filtering error can be guaranteed. In order to demonstrate the performance of the proposed adaptive T2FCMAC filter, it is tested in signal processing applications, including a nonlinear channel equalization system, a time-varying channel equalization system, and an adaptive noise cancellation system. The advantages of the proposed filter over the other adaptive filters are verified through simulations. PMID- 26540720 TI - Enhancing Heart-Beat-Based Security for mHealth Applications. AB - In heart-beat-based security, a security key is derived from the time difference between consecutive heart beats (the inter-pulse interval, IPI), which may, subsequently, be used to enable secure communication. While heart-beat-based security holds promise in mobile health (mHealth) applications, there currently exists no work that provides a detailed characterization of the delivered security in a real system. In this paper, we evaluate the strength of IPI-based security keys in the context of entity authentication. We investigate several aspects that should be considered in practice, including subjects with reduced heart-rate variability (HRV), different sensor-sampling frequencies, intersensor variability (i.e., how accurate each entity may measure heart beats) as well as average and worst-case-authentication time. Contrary to the current state of the art, our evaluation demonstrates that authentication using multiple, less entropic keys may actually increase the key strength by reducing the effects of intersensor variability. Moreover, we find that the maximal key strength of a 60 bit key varies between 29.2 bits and only 5.7 bits, depending on the subject's HRV. To improve security, we introduce the inter-multi-pulse interval (ImPI), a novel method of extracting entropy from the heart by considering the time difference between nonconsecutive heart beats. Given the same authentication time, using the ImPI for key generation increases key strength by up to 3.4 * (+19.2 bits) for subjects with limited HRV, at the cost of an extended key generation time of 4.8 * (+45 s). PMID- 26540721 TI - On the Analysis of Diseases and Their Related Geographical Data. AB - Electronic medical records (EMRs) store data related to patients information enrolled during their stay in health structures. Data stored into EMRs span from data crawled from biological laboratories to textual description of diseases and diagnostic device results (e.g., biomedical images). Each EMR is related to a diagnosis related group (DRG) record. A DRG record is a record associated with a citizen that has been cured in a hospital. It contains a code, called major diagnostic category (MDC), which summarizes the treated disease and allows to reimburse costs related to patient treatments during his staying in health structures. DRGs are used for administrative process (e.g., costs and reimbursement management) as well as disease monitoring. Associating diagnostic codes with external information (such as environmental and geographical data) and with information filtered from EMRs (e.g., biological results or analytes values) can be useful to monitor citizens wellness status. We propose a methodology to analyze such data based on a multistep process. First, we cross reference data by using a semantics-based clustering procedure, extract information from EMRs, and then, cluster them by looking for similar patterns of diseases. Then, biological records in each disease cluster are analyzed to evaluate intracluster similarity by selecting analytes typologies and values. Finally, biological data is related to diagnosis codes and geometrically projected in areas of interest in order to map calculated outlier patients. We applied the methodology on two case studies: 1) diagnosis codes and biochemical analytes of 20 000 biological analyses about hospitalized patients during one observation year and 2) the correlation between cardiovascular diseases and water quality in a southern Italian region. Preliminary findings show the effectiveness of our method. PMID- 26540722 TI - An Empirical Human Controller Model for Preview Tracking Tasks. AB - Real-life tracking tasks often show preview information to the human controller about the future track to follow. The effect of preview on manual control behavior is still relatively unknown. This paper proposes a generic operator model for preview tracking, empirically derived from experimental measurements. Conditions included pursuit tracking, i.e., without preview information, and tracking with 1 s of preview. Controlled element dynamics varied between gain, single integrator, and double integrator. The model is derived in the frequency domain, after application of a black-box system identification method based on Fourier coefficients. Parameter estimates are obtained to assess the validity of the model in both the time domain and frequency domain. Measured behavior in all evaluated conditions can be captured with the commonly used quasi-linear operator model for compensatory tracking, extended with two viewpoints of the previewed target. The derived model provides new insights into how human operators use preview information in tracking tasks. PMID- 26540723 TI - Inference With Collaborative Model for Interactive Tumor Segmentation in Medical Image Sequences. AB - Segmenting organisms or tumors from medical data (e.g., computed tomography volumetric images, ultrasound, or magnetic resonance imaging images/image sequences) is one of the fundamental tasks in medical image analysis and diagnosis, and has received long-term attentions. This paper studies a novel computational framework of interactive segmentation for extracting liver tumors from image sequences, and it is suitable for different types of medical data. The main contributions are twofold. First, we propose a collaborative model to jointly formulate the tumor segmentation from two aspects: 1) region partition and 2) boundary presence. The two terms are complementary but simultaneously competing: the former extracts the tumor based on its appearance/texture information, while the latter searches for the palpable tumor boundary. Moreover, in order to adapt the data variations, we allow the model to be discriminatively trained based on both the seed pixels traced by the Lucas-Kanade algorithm and the scribbles placed by the user. Second, we present an effective inference algorithm that iterates to: 1) solve tumor segmentation using the augmented Lagrangian method and 2) propagate the segmentation across the image sequence by searching for distinctive matches between images. We keep the collaborative model updated during the inference in order to well capture the tumor variations over time. We have verified our system for segmenting liver tumors from a number of clinical data, and have achieved very promising results. The software developed with this paper can be found at http://vision.sysu.edu.cn/projects/med interactive-seg/. PMID- 26540724 TI - Data Randomization and Cluster-Based Partitioning for Botnet Intrusion Detection. AB - Botnets, which consist of remotely controlled compromised machines called bots, provide a distributed platform for several threats against cyber world entities and enterprises. Intrusion detection system (IDS) provides an efficient countermeasure against botnets. It continually monitors and analyzes network traffic for potential vulnerabilities and possible existence of active attacks. A payload-inspection-based IDS (PI-IDS) identifies active intrusion attempts by inspecting transmission control protocol and user datagram protocol packet's payload and comparing it with previously seen attacks signatures. However, the PI IDS abilities to detect intrusions might be incapacitated by packet encryption. Traffic-based IDS (T-IDS) alleviates the shortcomings of PI-IDS, as it does not inspect packet payload; however, it analyzes packet header to identify intrusions. As the network's traffic grows rapidly, not only the detection-rate is critical, but also the efficiency and the scalability of IDS become more significant. In this paper, we propose a state-of-the-art T-IDS built on a novel randomized data partitioned learning model (RDPLM), relying on a compact network feature set and feature selection techniques, simplified subspacing and a multiple randomized meta-learning technique. The proposed model has achieved 99.984% accuracy and 21.38 s training time on a well-known benchmark botnet dataset. Experiment results demonstrate that the proposed methodology outperforms other well-known machine-learning models used in the same detection task, namely, sequential minimal optimization, deep neural network, C4.5, reduced error pruning tree, and randomTree. PMID- 26540725 TI - Creating Discriminative Models for Time Series Classification and Clustering by HMM Ensembles. AB - Classification of temporal data sequences is a fundamental branch of machine learning with a broad range of real world applications. Since the dimensionality of temporal data is significantly larger than static data, and its modeling and interpreting is more complicated, performing classification and clustering on temporal data is more complex as well. Hidden Markov models (HMMs) are well-known statistical models for modeling and analysis of sequence data. Besides, ensemble methods, which employ multiple models to obtain the target model, revealed good performances in the conducted experiments. All these facts are a high level of motivation to employ HMM ensembles in the task of classification and clustering of time series data. So far, no effective classification and clustering method based on HMM ensembles has been proposed. Moreover, employing the limited existing HMM ensemble methods has trouble separating models of distinct classes as a vital task. In this paper, according to previous points a new framework based on HMM ensembles for classification and clustering is proposed. In addition to its strong theoretical background by employing the Renyi entropy for ensemble learning procedure, the main contribution of the proposed method is addressing HMM-based methods problem in separating models of distinct classes by considering the inverse emission matrix of the opposite class to build an opposite model. The proposed algorithms perform more effectively compared to other methods especially other HMM ensemble-based methods. Moreover, the proposed clustering framework, which derives benefits from both similarity-based and model-based methods, together with the Renyi-based ensemble method revealed its superiority in several measurements. PMID- 26540726 TI - The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3. AB - Three genes, CCM1, CCM2, and CCM3, interact genetically and biochemically and are mutated in cerebral cavernous malformations (CCM). A recently described member of this CCM family of proteins, CCM2-like (CCM2L), has high homology to CCM2. Here we show that its relative expression in different tissues differs from that of CCM2 and, unlike CCM2, the expression of CCM2L in endothelial cells is regulated by density, flow, and statins. In vitro, both CCM2L and CCM2 bind MEKK3 in a complex with CCM1. Both CCM2L and CCM2 interfere with MEKK3 activation and its ability to phosphorylate MEK5, a downstream target. The in vivo relevance of this regulation was investigated in zebrafish. A knockdown of ccm2l and ccm2 in zebrafish leads to a more severe "big heart" and circulation defects compared with loss of function of ccm2 alone, and also leads to substantial body axis abnormalities. Silencing of mekk3 rescues the big heart and body axis phenotype, suggesting cross-talk between the CCM proteins and MEKK3 in vivo. In endothelial cells, CCM2 deletion leads to activation of ERK5 and a transcriptional program that are downstream of MEKK3. These findings suggest that CCM2L and CCM2 cooperate to regulate the activity of MEKK3. PMID- 26540727 TI - Plant Raf-like kinase integrates abscisic acid and hyperosmotic stress signaling upstream of SNF1-related protein kinase2. AB - Plant response to drought and hyperosmosis is mediated by the phytohormone abscisic acid (ABA), a sesquiterpene compound widely distributed in various embryophyte groups. Exogenous ABA as well as hyperosmosis activates the sucrose nonfermenting 1 (SNF1)-related protein kinase2 (SnRK2), which plays a central role in cellular responses against drought and dehydration, although the details of the activation mechanism are not understood. Analysis of a mutant of the moss Physcomitrella patens with reduced ABA sensitivity and reduced hyperosmosis tolerance revealed that a protein kinase designated "ARK" (for "ABA and abiotic stress-responsive Raf-like kinase") plays an essential role in the activation of SnRK2. ARK encoded by a single gene in P. patens belongs to the family of group B3 Raf-like MAP kinase kinase kinases (B3-MAPKKKs) mediating ethylene, disease resistance, and salt and sugar responses in angiosperms. Our findings indicate that ARK, as a novel regulatory component integrating ABA and hyperosmosis signals, represents the ancestral B3-MAPKKKs, which multiplied, diversified, and came to have specific functions in angiosperms. PMID- 26540728 TI - Single-molecule visualization of RecQ helicase reveals DNA melting, nucleation, and assembly are required for processive DNA unwinding. AB - DNA helicases are motor proteins that unwind double-stranded DNA (dsDNA) to reveal single-stranded DNA (ssDNA) needed for many biological processes. The RecQ helicase is involved in repairing damage caused by DNA breaks and stalled replication forks via homologous recombination. Here, the helicase activity of RecQ was visualized on single molecules of DNA using a fluorescent sensor that directly detects ssDNA. By monitoring the formation and progression of individual unwinding forks, we observed that both the frequency of initiation and the rate of unwinding are highly dependent on RecQ concentration. We establish that unwinding forks can initiate internally by melting dsDNA and can proceed in both directions at up to 40-60 bp/s. The findings suggest that initiation requires a RecQ dimer, and that continued processive unwinding of several kilobases involves multiple monomers at the DNA unwinding fork. We propose a distinctive model wherein RecQ melts dsDNA internally to initiate unwinding and subsequently assembles at the fork into a distribution of multimeric species, each encompassing a broad distribution of rates, to unwind DNA. These studies define the species that promote resection of DNA, proofreading of homologous pairing, and migration of Holliday junctions, and they suggest that various functional forms of RecQ can be assembled that unwind at rates tailored to the diverse biological functions of RecQ helicase. PMID- 26540729 TI - Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events. AB - Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions. PMID- 26540730 TI - On artifacts in single-molecule force spectroscopy. AB - In typical force spectroscopy experiments, a small biomolecule is attached to a soft polymer linker that is pulled with a relatively large bead or cantilever. At constant force, the total extension stochastically changes between two (or more) values, indicating that the biomolecule undergoes transitions between two (or several) conformational states. In this paper, we consider the influence of the dynamics of the linker and mesoscopic pulling device on the force-dependent rate of the conformational transition extracted from the time dependence of the total extension, and the distribution of rupture forces in force-clamp and force-ramp experiments, respectively. For these different experiments, we derive analytic expressions for the observables that account for the mechanical response and dynamics of the pulling device and linker. Possible artifacts arise when the characteristic times of the pulling device and linker become comparable to, or slower than, the lifetimes of the metastable conformational states, and when the highly anharmonic regime of stretched linkers is probed at high forces. We also revisit the problem of relating force-clamp and force-ramp experiments, and identify a linker and loading rate-dependent correction to the rates extracted from the latter. The theory provides a framework for both the design and the quantitative analysis of force spectroscopy experiments by highlighting, and correcting for, factors that complicate their interpretation. PMID- 26540731 TI - Distinct functionality of neutrophils in multiple sclerosis and neuromyelitis optica. AB - BACKGROUND: In contrast to multiple sclerosis (MS), lesions in neuromyelitis optica (NMO) frequently contain neutrophils. However, the phenotypic profile of neutrophils in these two distinct pathologies remains unknown. OBJECTIVE: Our aim is to better understand the potential contribution of neutrophils to NMO and MS pathology. METHODS: We performed the first functional analysis of blood neutrophils in NMO and MS, including evaluation of neutrophil immune response (fMLP receptor, TLR2), chemotaxis and migration (CXCR1, CD62L, CD43), regulation of complement (CD46, CD55, CD59), respiratory burst, phagocytosis and degranulation. RESULTS: Compared with healthy controls (HC), neutrophils in NMO and MS show an activated phenotype characterized by an increased surface expression of TLR2 and fMLP receptor. However, contrary to MS neutrophils, NMO neutrophils show reduced adhesion and migratory capacity as well as decreased reduced production of reactive oxygen species (respiratory burst) and degranulation. CONCLUSION: Although NMO and MS neutrophils display an activated phenotype in comparison with HC, NMO neutrophils show a compromised functionality when compared with MS patients. These results suggest a distinct functional profile of neutrophils in MS and NMO. PMID- 26540732 TI - Baseline clinical status as a predictor of methylprednisolone response in multiple sclerosis relapses. AB - BACKGROUND: To date, there are no available factors to predict the outcome after multiple sclerosis relapse. AIM: To investigate factors that may be useful for predicting response to methylprednisolone treatment, following a relapse of multiple sclerosis (MS). METHODS: The study included 48 MS patients enrolled in a double-blind multicenter trial to receive intravenous versus oral high-dose methylprednisolone treatment. Associations were sought between the disability status prior to relapse and the relapse severity, determined by changes in the Expanded Disability Status Scale (EDSS) score, as well as the improvements after treatment. We also analyzed the relationships between the number of magnetic resonance imaging (MRI) gadolinium-enhancing lesions (Gd+) and improvement. RESULTS: A higher EDSS score before relapse was associated with more severe relapses (p = 0.04) and less marked improvement (odds ratio (OR) 1.8; 95% CI (1.2 2.2); p = 0.05) after methylprednisolone treatment. Relapse severity (p = 0.29) and the number of Gd+ lesions at relapse (p = 0.41) were not related with improvement. CONCLUSIONS: Clinical baseline status prior to MS relapse is a predictor of response to methylprednisolone treatment. PMID- 26540733 TI - Why does multiple sclerosis only affect human primates? AB - BACKGROUND: Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as insights might be gained into the elusive event(s) that trigger(s) MS. A well-established difference between the human primate (Homo sapiens) and non-human primates is that humans are unable to synthesize the sialic acid N-glycolylneuraminic acid (Neu5Gc). VIEWPOINT: We propose the concept that long-term ingestion by human primates of the foreign Neu5Gc, via red meat consumption, is an ignored environmental risk factor for MS. Conceptually, incorporation of dietary Neu5Gc into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit, creates targets for binding of de novo synthesized heterophilic anti-NeuGc antibodies. Binding of the antibodies can cause BBB leakage and destabilization of the axon-myelin coupling. The ensuing cytodegeneration and release of self-antigens could be a start of the characteristic pathological features of MS. PMID- 26540734 TI - Force-Velocity Relationship of Upper Body Muscles: Traditional Versus Ballistic Bench Press. AB - This study aimed to (1) evaluate the linearity of the force-velocity relationship, as well as the reliability of maximum force (F0), maximum velocity (V0), slope (a), and maximum power (P0); (2) compare these parameters between the traditional and ballistic bench press (BP); and (3) determine the correlation of F0 with the directly measured BP 1-repetition maximum (1RM). Thirty-two men randomly performed 2 sessions of traditional BP and 2 sessions of ballistic BP during 2 consecutive weeks. Both the maximum and mean values of force and velocity were recorded when loaded by 20-70% of 1RM. All force-velocity relationships were strongly linear (r > .99). While F0 and P0 were highly reliable (ICC: 0.91-0.96, CV: 3.8-5.1%), lower reliability was observed for V0 and a (ICC: 0.49-0.81, CV: 6.6-11.8%). Trivial differences between exercises were found for F0 (ES: < 0.2), however the a was higher for the traditional BP (ES: 0.68-0.94), and V0 (ES: 1.04-1.48) and P0 (ES: 0.65-0.72) for the ballistic BP. The F0 strongly correlated with BP 1RM (r: 0.915-0.938). The force-velocity relationship is useful to assess the upper body maximal capabilities to generate force, velocity, and power. PMID- 26540735 TI - To What Extent Can the Use of a Mobility Assistance Dog Reduce Upper Limb Efforts When Manual Wheelchair Users Ascend a Ramp? AB - Biomechanical evidence is needed to determine to what extent the use of a mobility assistance dog (AD(Mob)) may minimize mechanical loads and muscular demands at the upper limbs among manual wheelchair users. This study quantified and compared upper limb efforts when propelling up a ramp with and without an AD(Mob) among manual wheelchair users. Ten manual wheelchair users with a spinal cord injury who own an AD(Mob) ascended a ramp with and without their AD(Mob). The movements of the wheelchair and upper limbs were captured and the forces applied at the pushrims were recorded to compute shoulder mechanical loading. Muscular demand of the pectoralis major, anterior deltoid, biceps, and the triceps was normalized against the maximum electromyographic values. The traction provided by the AD(Mob) significantly reduced the total force applied at the pushrim and its tangential component while the mechanical effectiveness remained similar. The traction provided by the AD(Mob) also resulted in a significant reduction in shoulder flexion, internal rotation, and adduction moments. The muscular demands of the anterior deltoid, pectoralis major, biceps, and triceps were significantly reduced by the traction provided by the AD(Mob). The use of AD(Mob) represents a promising mobility assistive technology alternative to minimize upper limb mechanical loads and muscular demands and optimize performance during wheelchair ramp ascent. PMID- 26540736 TI - Biomechanical Testing of Distal Radius Fracture Treatments: Boundary Conditions Significantly Affect the Outcome of In Vitro Experiments. AB - The variety of experimental setups used during in vitro testing of distal radius fracture treatments impairs interstudy comparison and might lead to contradictory results. Setups particularly differ with respect to their boundary conditions, but the influence on the experimental outcome is unknown. The aim of this biomechanical study was to investigate the effects of 2 common boundary conditions on the biomechanical properties of an extra-articular distal radius fracture treated using volar plate osteosynthesis. Uniaxial compression tests were performed on 10 synthetic radii that were randomized into a proximally constrained group (ProxConst) or proximally movable group (ProxMove). The load was applied distally through a ball joint to enable distal fragment rotation. A significantly larger (ProxConst vs ProxMove) stiffness (671.6 +/- 118.9 N.mm(-1) vs 259.6 +/- 49.4 N.mm(-1)), elastic limit (186.2 +/- 24.4 N vs 75.4 +/- 20.2 N), and failure load (504.9 +/- 142.5 N vs 200.7 +/- 49.0 N) were found for the ProxConst group. The residual tilt did not differ significantly between the 2 groups. We concluded that the boundary conditions have a profound impact on the experimental outcome and should be considered more carefully in both study design and interstudy comparison. PMID- 26540737 TI - The Effects of Pilates Training on Balance Control and Self-Reported Health Status in Community-Dwelling Older Adults: A Randomized Controlled Trial. AB - OBJECTIVES: To evaluate the effect of a group-based Pilates training program on balance control and health status in healthy older adults. DESIGN: A single blind, randomized, controlled trial. SETTING: General community. PARTICIPANTS: A total of 88 community-dwelling older adults (age 71.15 +/- 4.30 years), without evidence of functional balance impairment, were recruited and allocated at random to a Pilates intervention group (n = 44) or a control group (n = 44). INTERVENTION: The Pilates intervention group received 36 training sessions over three months (3 sessions a week), while the control group did not receive any intervention. OUTCOME MEASURES: Standing upright postural stability, performance based measures of balance, and self-reported health status was assessed in both groups at baseline and at the end of the intervention period. RESULTS: Compared with the control group, the Pilates intervention did not improve postural stability, baseline functional measures of balance, or health status. CONCLUSIONS: The results suggest that because Pilates training is not task specific, it does not improve balance control or balance function in independent older adults. PMID- 26540738 TI - Poor Muscle Strength and Low Physical Activity Are the Most Prevalent Frailty Components in Community-Dwelling Older Adults. AB - OBJECTIVE: To determine the prevalence of five physical frailty phenotype components and to assess the relationship between them and other clinical factors. METHOD: A population-based cross-sectional study was performed. Subjects 75 years and older were randomly selected from primary care databases (with sampling stratified by gender). Physical frailty phenotypes were assessed using Fried's criteria. Sociodemographic data, comorbidities, nutritional status, and functional capacity were assessed. RESULTS: 126 subjects were recruited (47% women). Prevalence rates were poor muscle strength: 50%; low physical activity: 29%; slow gait: 28%; exhaustion: 27%; and weight loss: 5%. Prefrailty and frailty prevalence rates were 35.7% and 29.4%, respectively. Poor muscle strength and low physical activity showed a close relationship and concordance (kappa = 0.92). Most frailty components were associated with outdoor activity, hours walked daily, and certain comorbidities. CONCLUSIONS: Poor muscle strength was the most prevalent frailty component and was closely associated with physical activity, suggesting that training programs may revert or prevent the frailty process. PMID- 26540739 TI - [Neck pain]. PMID- 26540741 TI - The Science and the Future of the Research Track at ONS Congress. PMID- 26540742 TI - Performance of transgenic TgTau-P301L mice in a 5-choice serial reaction time task (5-CSRTT) as a model of Alzheimer's disease. AB - Alzheimer's disease is increasing to epidemic levels with an estimated 36 million people affected worldwide (Wimo 2010). The aetiology of the disease is not known, which is hindering the progression of the treatment. This study is a longitudinal investigation into the performance of TgTauP301L mice as an animal model of Alzheimer's disease on the computer automated touchscreen 5-choice serial reaction time task (5-CSRTT). TgTauP301L mice have a single tau mutation in the P301L gene and develop the tau pathology that represents the observed tauopathy in patients with Alzheimer's disease. The aim of the investigation is to observe if tau pathology in the TgTauP301L mice causes a cognitive impairment in attention and executive function and at what stage this can be identified by the 5-CSRTT task. This will establish if the animals can be used as a therapeutic model for pre-clinical drug trials and help to identify an early indicator and intervention point in patients with Alzheimer's disease. The animals have previously been studied at 5-months and no differences between performances of the TgTauP301L mice and wild type mice were found (unpublished data). This study measured the performance of the animals at 7-months which is when the tauopathy begins to develop in TgTauP301L mice (Murakami 2005). The results of this study showed that there was no deficit in the performance of the TgTauP301L compared to the wild type mice and there had been no change in the animals' performance compared to at 5-months. The animals will be retested at 12-months once the pathology has extensively spread to see if the tauopathy causes a deficit in performance. PMID- 26540740 TI - Marine Compounds and Cancer: Where Do We Stand? PMID- 26540743 TI - Authors' reply. PMID- 26540744 TI - Authors' reply. PMID- 26540745 TI - Connecting care. PMID- 26540746 TI - Preventing hospital readmissions. How to be part of the solution. PMID- 26540747 TI - HIPAA BREACH. Secure data & prevent fines--here's how. PMID- 26540748 TI - OFFICE OF CIVIL RIGHTS: HIPAA AUDITS. PMID- 26540749 TI - Strengthen your staff: Six strategies to inspire accountability and effort. PMID- 26540751 TI - Financing practice improvements the right way. PMID- 26540750 TI - Three ways to avoid employee disputes. PMID- 26540752 TI - CAN THIS ENCOUNTER BE BILLED INCIDENT-TO? PMID- 26540753 TI - Hiring an NP or PA for your medical practice. PMID- 26540754 TI - Clinical Economics. Rheumatoid Arthritis. PMID- 26540755 TI - FOUR HEALTHCARE CONSEQUENCES OF KING V. BURWELL DECISION. PMID- 26540756 TI - Message from the Editors. PMID- 26540757 TI - Hans Helge, MD, PhD (1935-2015). PMID- 26540758 TI - Lawson Wilkins, MD, 1894-1963: A Founding Father of Pediatric Endocrinology. PMID- 26540759 TI - Bone Age Estimation for Whom by Whom? By Which Method? AB - Bone (skeletal) age determination is the simplest and most used index for the assessment of developmental and physiological age in healthy children and those with growth disorders. At present the test is done by manual or automated reading of the hand and wrist X-rays, necessitating two visits by the child: to the pediatrician and radiology departments. A newly developed simple quantitative ultrasound technique (QUST) using several hand and wrist bones, which can be performed in the pediatrician's office could combine the child's growth and biological age evaluation in one visit. PMID- 26540760 TI - Chromosomal Microarray Analysis (CMA) a Clinical Diagnostic Tool in the Prenatal and Postnatal Settings. AB - Chromosomal microarray analysis (CMA) is a technology used for the detection of clinically-significant microdeietions or duplications, with a high sensitivity for submicroscopic aberrations. It is able to detect changes as small as 5-10Kb in size - a resolution up to 1000 times higher than that of conventional karyotyping. CMA is used for uncovering copy number variants (CNVs) thought to play an important role in the pathogenesis of a variety of disorders, primarily neurodevelopmental disorders and congenital anomalies. CMA may be applied in the prenatal or postnatal setting, with unique benefits and limitations in each setting. The growing use of CMA makes it essential for practicing physicians to understand the principles of this technology and be aware of its powers and limitations. PMID- 26540761 TI - Association of Turner Syndrome and Growth Hormone Deficiency: A Review. AB - Turner syndrome (TS) is an important cause of short stature in girls. Patients with TS most often do not have growth hormone deficiency (GHD). Testing GH secretion is not indicated despite the presence of short stature. In the last 20 years only three cases were reported with this association in Pubmed. We describe a case of an 11 year old girl with short stature and karyotype confirmed TS: 45,X(16)46,X,i(X)(ql0)(13). Because her growth velocity was low (-3 SD), we evaluated the GH response with stimulating tests and the results were under the normal range. These findings were compatible with GHD. It is important to check for GHD in patients with TS whenever the growth velocity is low for age and sex. PMID- 26540762 TI - Precocious Puberty Following Traumatic Brain Injury in Early Childhood: A Review of the Literature. AB - AIMS OF THE REVIEW: The intent of the current manuscript is to review the cases of central precocious puberty (CPP) in early childhood following traumatic brain injury (TBI). SEARCH OF THE LITERATURE: The MEDLINE database was accessed through PubMed in April 2015. Results were not restricted to the date and language of the articles. For the first search we utilized MeSH terms "precocious puberty" in conjunction with "traumatic brain injury" and with "endocrine consequences". Reference lists were reviewed and relevant papers were also consulted to find additional studies and data. In selected cases the corresponding author was contacted by email. RESULTS: In our systematic review, only a few case reports or small case series have highlighted a link between TBI and hypothalamic-pituitary hormone abnormalities. Fourteen reported children were females and 8 were males. The majority of patients reported had severe TBI, assessed by Glasgow Coma Scale or structural injury (skull fractures, intracranial hemorrhage or cerebral injury) reported on computerized tomography or magnetic resonance imaging scans. The pathogenic mechanism of precocious puberty has not yet been determined. An increased pressure on the hypothalamic-pituitary area with loss of normal childhood hypothalamic inhibition of pituitary gonadotropins could be one of the factors responsible for CPP after TBI. CONCLUSIONS: The current review highlights the importance of close clinical follow-up to evaluate the rate of linear growth and pubertal development after TBI. Although, precocious puberty appears to be rare after TBI, prevalence should ideally be assessed by longitudinal follow-up of a large population. Therefore, further multicenter and multidisciplinary studies are required to explore in detail the true incidence and the possible mechanisms of CPP after TBI. Because precocious puberty can be detected on clinical assessment during childhood, a pragmatic approach would be for family physicians to monitor growth and development in children after TBI. Inasmuch as precocity is mediated through the hypothalamic-pituitary pathways, use of LH-RH analogue therapy should be effective in arresting pubertal progression. PMID- 26540763 TI - Should Patients with Trichorhinophalangeal Syndrome be Tested for Growth Hormone Deficiency? AB - Type 1 Trichorhinophalangeal syndrome (TRPS) is characterized by typical facial and skeletal abnormalities. These patients frequently exhibit short stature; however, only one case with growth hormone (GH) deficiency can be found in the literature. Our patient is a 10-year-old girl with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity: c. 1198C>T (p. Gln400X) and c.2086C>T (p. Arg696X). She has an additional GH deficiency. The patient is short in stature, with a growth velocity of 1.5 cm per year (SDS - 4.07), a bone age of 4.5 years, and she shows no response to the GH stimulation tests. According to a previous report of an identical case, catch-up growth will occur after beginning GH treatment. We believe that GH stimulation tests should be performed on patients with TRPS1 exhibiting a growth velocity below the normal range expected for their age and sex. If the result is subnormal, then GH therapy should be attempted. PMID- 26540764 TI - Nephrolithiasis and Nephrocalcinosis in Children - Metabolic and Genetic Factors. AB - Diagnosis and management of pediatric nephrolithiasis/nephrocalcinosis is a very complex and challenging task for every pediatrician. It is based on correct. disease history taking, which may guide to the mode of inheritance (dominant, recessive, x-linked). Ethnicity and consanguinity should also be investigated since they predispose to high prevalence of certain disorders. One should always begin with cheap and available screening tests. Herein we will review clinical, biochemical, metabolic and genetic characteristics of the inherited diseases which lead to nephrolithiasis/nephrocalcinosis, such as: idiopathic hypercalciuria, renal hypophosphatemia, renal tubular acidosis, idiopathic infantile hypercalcemia, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypocitraturia, cystinuria, primary hyperoxaluria and renal hypouricemia. Modern genetic techniques such as next generation sequencing enable nowadays diagnosis of rare disease using only a blood sample, trough massive parallel resequencing of many genes. This is very helpful for anuric patients or on dialysis where blood and urine biochemistry are not informative. Genetic testing also replaces invasive liver biopsy or unpleasant acidification tests and enables prenatal or early postnatal diagnosis. PMID- 26540765 TI - Response to "Propranolol Induced Hypoglycemia" by Amir Horev, MD, Alon Haim, MD, Alex Zvulunov, MD. PMID- 26540766 TI - Reply of the authors. PMID- 26540767 TI - 2015 Annual Meeting of the Pediatric Endocrine Society San Diego, CA (April 25 27, 2015) Selected Highlights. PMID- 26540768 TI - Key mission for military EHR contract: Lead the way to interoperability. PMID- 26540769 TI - Advocates split with health plans, states over Medicaid managed-care rules. PMID- 26540770 TI - Providers back bill alerting Medicare patients about observation stays. PMID- 26540771 TI - Insurers, PBMs continue to fight for bigger, better drug price discounts. PMID- 26540772 TI - Capella sale to REIT shows hospitals seek to monetize real estate. PMID- 26540773 TI - Behavioral health behind bars and beyond. PMID- 26540774 TI - 'SWIVEL CHAIR' INTEROPERABILITY. PMID- 26540776 TI - On Medicare's 50th birthday, Blues plans remain key to the programs success. PMID- 26540775 TI - The benefits of rate regulation. PMID- 26540777 TI - Giving newborns distinct name cuts errors. PMID- 26540778 TI - Meet the sheriff who runs one of America's largest psych facilities. PMID- 26540779 TI - Largest home-health companies. Ranked by most-recent total net revenue based on federal filings. PMID- 26540780 TI - CORPORATE WELLNESS PROGRAMS MAKE US UNWELL . PMID- 26540781 TI - The last lesson. PMID- 26540782 TI - FIGHTING BACK. PART 2. The Quest for Independence. Stake your claim to medical practice freedom. PMID- 26540783 TI - PRIME YOUR FEE SCHEDULE: FINDING HIDDEN REVENUE. PMID- 26540784 TI - PHYSICIAN RIGHTS IN THE OPEN PAYMENTS PROGRAM. PMID- 26540785 TI - Is meaningful use worth it? PMID- 26540786 TI - The new role physicians can't afford to ignore. PMID- 26540787 TI - Taking on risk: Understanding the new world of payments. PMID- 26540788 TI - LAST MINUTE ICD-10 CONVERSION TIPS. PMID- 26540789 TI - 5 STRATEGIES TO MAXIMIZE YOUR EHR. PMID- 26540790 TI - THE OPI0ID ABUSE EPIDEMIC. PROTECT YOURSELF FROM LIABILITY. PMID- 26540791 TI - THE POWER OF NURSES WORKING TOGETHER. PMID- 26540793 TI - The Change. PMID- 26540792 TI - HOUSE OF DELEGATES LAUNCHES A BRIGHT FUTURE FOR TNA. PMID- 26540794 TI - Foreword. Medical Philately--Introduction. PMID- 26540795 TI - Lord Dhanvantari--Physician of Gods and God of Ayurvedic Medicine (Vedic period). PMID- 26540796 TI - Hippocrates--Father of Medicine. PMID- 26540797 TI - Dioscorides (CA 54-68 AD). PMID- 26540798 TI - Aretaeus (130-200 CE). PMID- 26540799 TI - Claudius Galen (130-201 A.D.). PMID- 26540800 TI - Chorea-St. Vitus, Sydenham or Pandas? PMID- 26540801 TI - Rhazes (835-925 A.D). PMID- 26540802 TI - Avecenna (980-1037 A.D). PMID- 26540803 TI - Maimonides (1135-1204). PMID- 26540804 TI - Ibn-al-Nafis (1210-1288 AD) Originator of Pulmonary Circulation. PMID- 26540805 TI - Leonardo Da Vinci (1452-1519). PMID- 26540806 TI - Paracelsus (1493-1541). PMID- 26540807 TI - Garcia Da Orta (1502-1568). PMID- 26540808 TI - Michael Servetus--Discoverer of Pulmonary Circulation and a Heretic. PMID- 26540809 TI - Ambroise Pare (1510-1590). PMID- 26540810 TI - Andreas Vesalius (1514-1564). PMID- 26540811 TI - William Harvey. PMID- 26540812 TI - Nicolaas Tulp (1593-1674). PMID- 26540813 TI - Marcello Malpighi (1628-1694). PMID- 26540814 TI - Anton Van Leeuwenhoek (1632-1723). PMID- 26540815 TI - Niels Stensen (1638-1686). PMID- 26540816 TI - Hermann Boerhaave (1668-1738). PMID- 26540817 TI - James Lind (1716-1794) & Captain Cook (1728-1779). PMID- 26540818 TI - Munchhausen Syndrome, Karl Frederic Von Munchhausen (1720 - 1797). PMID- 26540819 TI - Joseph Leopold Auenbrugger--Founder of Percussion Technique. PMID- 26540820 TI - Antoine Lavoisier--Father of Modern Chemistry. PMID- 26540821 TI - Lazzaro Spallanzani (1729-1799). PMID- 26540822 TI - Joseph Priestly--Discoverer of Oxygen. PMID- 26540823 TI - Anaesthesia and Critical Care--Oxygen Discovery. PMID- 26540824 TI - Edward Jenner--Father of Immunology. PMID- 26540825 TI - Dominique J Larrey (1766-1842). PMID- 26540826 TI - Jean Corvisart (1755-1821). PMID- 26540827 TI - RT Laennec (1781 - 1826). PMID- 26540829 TI - Christian Doppler (1803-1853). PMID- 26540828 TI - Johannes Purkinje (1787-1869). PMID- 26540830 TI - Carl Rokitansky, A Premier Pathologist. PMID- 26540831 TI - Josef Dietl (1804 - 1878)--Medical Reformer and "His Crisis". PMID- 26540832 TI - Joseph Skoda (1805-1881). PMID- 26540833 TI - Alfred de Musset's Sign. PMID- 26540834 TI - James Young Simpson & Painless Labour. PMID- 26540835 TI - Claude Bernard (1813-1878). PMID- 26540836 TI - Gerhard Armauer Hansen (1814-1912). PMID- 26540837 TI - Discovery of Anaesthesia- Intriguing Story. PMID- 26540838 TI - Ferdinand Von Hebra--Founder of Classical Dermatology. PMID- 26540839 TI - Brown-Sequard & His Syndrome. PMID- 26540840 TI - Pettenkofer--Father of Experimental Hygiene. PMID- 26540841 TI - Ignaz Semmelweis--Hand washing Pioneer. PMID- 26540842 TI - Donders--Father of Clinical Refraction. PMID- 26540843 TI - Caventou, Pelletier &--History Of Quinine. PMID- 26540844 TI - Rudolf Virchow (1821-1902). PMID- 26540845 TI - H.L. Helmholtz (1821-1894). PMID- 26540846 TI - John Gregor Mendel (1822-1884). PMID- 26540847 TI - Louis Pasteur (1822 - 1895). PMID- 26540848 TI - Theodor Bilharz--(1825-1862). PMID- 26540849 TI - J.M. Charcot (1825 - 1893). PMID- 26540850 TI - Lord Lister (1827-1912). PMID- 26540851 TI - Alfred Nobel (1833-1896). PMID- 26540852 TI - Camillo Golgi and Ramon Y Cajal who Peeped into the Mysterious World of Nervous System. PMID- 26540853 TI - Paul Ehrlich (1854-1915). PMID- 26540854 TI - Dr. Victor Babes, Discoverer of Babesia. PMID- 26540855 TI - Christiaan Eijkman (1858-1930). PMID- 26540856 TI - Discovery of Colloids. PMID- 26540857 TI - Dr. Piraja Da Silva (1873-1961). PMID- 26540858 TI - Egaz Moniz. PMID- 26540859 TI - Robert Barany Father of Otoneurology and Vestibular Functions. PMID- 26540860 TI - Bidhan Chandra Roy & National Doctors Day. PMID- 26540861 TI - Sir Ram Nath Chopra (1882-1973). PMID- 26540862 TI - George Nicholas Papanicolaou, Father of Modern Cytopathology. PMID- 26540863 TI - Corticosteroids. PMID- 26540864 TI - Anaesthesia and Critical Care. PMID- 26540865 TI - Raman Effect in Medicine and its Future. PMID- 26540866 TI - Dr. Yellapragada Subbarow (1895-1948). PMID- 26540867 TI - Georg Von Bekesy--Visualisation of Hearing. PMID- 26540868 TI - Dr. Dwarkanath Kotnis. PMID- 26540869 TI - Virginia Apgar (1909-1974). PMID- 26540870 TI - Discovery of Immunoglobulins (Antibodies). PMID- 26540871 TI - Discovery of Mediators of Sepsis. PMID- 26540872 TI - Kidney Transplantation. PMID- 26540873 TI - Luc Montagnier--Discoverer of HIV Virus. PMID- 26540874 TI - Diabetes: From Ancient Egypt to the 18th Century. PMID- 26540875 TI - Diabetes : Modern Times. PMID- 26540876 TI - Diabetes : Modern Times. PMID- 26540877 TI - Diabetes : Modern Times. PMID- 26540878 TI - Thyroid: From Hellenistic Greece to Renaissance. PMID- 26540879 TI - Thyroid: From 16th to 20th Century. PMID- 26540880 TI - Genitalia and Infertility. PMID- 26540881 TI - Adrenal Gland. PMID- 26540882 TI - Genitalia and Infertility. PMID- 26540883 TI - Pituitary. PMID- 26540884 TI - Obesity. PMID- 26540885 TI - Application of Diagnostic Techniques to Endocrinology. PMID- 26540886 TI - Application of Diagnostic Techniques to Endocrinology. PMID- 26540887 TI - Endocrine International Congresses. PMID- 26540888 TI - Modern Plague--HIV Infection. PMID- 26540889 TI - [The conflict of the three "E's"]. PMID- 26540890 TI - [ARCSTERILE: A COST-EFFECTIVE LUXURY]. AB - OBJECTIVE: The aim of this study is to evaluate the safety, economic profitability, and cost-effectiveness of the controlled ambient surgical cabin ArcSterile. MATERIALS AND METHODS: Retrospective observational study comparing the profitability of surgical procedures using the ArcSterile* with those using the operating room throughout a 12-month period by analysing the following variables: total number of treated patients, delay in surgical assistance delay and the cost per procedure. RESULTS: Throughout a 12-month period, a total number of 2011 surgical procedures were performed with the ArcSterile, and 1736 surgical procedures were performed in the conventional operating room. Minor ocular surgeries including chalazia, pterigium, intravitreal injections and others were considered, whereas cataract and vitrectomy surgeries were disregarded. The use of the ArcSterile* was associated with an increase of 14% in the number of surgeries. The cost per hour of the use of the ArcSterile* was 30.75 euro, whereas it was 142.78 euro for the coriventional operating room. CONCLUSIONS: The ArcSterile* may allow to treat more patients and to treat them earlier compared with the conventional operating room, optimizing the use of the latest for patients who need a more complex surgery. We estimated an economic impact of 134 121.39 euro savings during the 12-month period of analysis. The use of the ArcSterile* surgical cabin for outpatient ocularsurgery may represent an effective and efficient alternative to the operating room with many clinical and economic benefits. PMID- 26540891 TI - [MANAGEMENT OF HEALTHCARE WASTE IN THE HOSPITAL SETTING. UNDERSTANDING RISK MANAGEMENT]. AB - The sanitary waste represents a potential hazard for health workers. Given the high risk of infection in labor accidents, the correct management of sanitary waste minimizes this risk and improves labor and environment conditions. OBJECTIVE: To identify risk perception with health professionals in relation to the advanced sorting and management of healthcare waste (HW). METHODOLOGY: The current study is a descriptive, cross-sectional. The sample size was 177 health workers (nurse assistants, nurses, physicians, lab technicians) from three hospitals in Barcelona (Catalonia). Homemade questionnaire and questions with a free and spontaneous association and incomplete sentences were used to analyze labor variables, perception of risk and personal security through a Likert scale. RESULTS: Using a score from 1 (the lowest perception of risk) to 5 (the high perception of risk) to assess the risk perception, the average value for nurse assistants, nurses, physicians, and lab technicians was 3.71, 3.75, 3.83 and 4.03, respectively. Referring to items with free and spontaneous response association, 44.8% of workers consider HW as a biohazard, 29.6% consider it as waste material, 22.1% state that it must be managed properly and 3.5% described it as unknown residues. CONCLUSION: The results suggest that all health professionals generally have a perception of high risk. The lab technicians have a higher perception of the real risk of inadequate management of HW A 63.2% report that everyone has to make a proper management to preserve their occupational health; the 59% consider that the HW are a biological risk to the general population and only the 47.8% that are harmful to public health. Although it should be noted that only 44.8% think that HW are toxic and dangerous. PMID- 26540893 TI - [Four testimonies and a fiction]. PMID- 26540892 TI - [Nurses in war situations]. PMID- 26540894 TI - [PREVALENCE OF SNUFF IN PATIENTS TREATED IN HOSPITAL CONSULTATION DAY AND RHEUMATOLOGY NURSING]. AB - OBJECTIVES: To assess the prevalence of tobacco consumption in patients with inflammatory arthritis treated in our department and to raise awareness against tobacco in order to reduce the maximum number of active smokers. METHOD: A tobacco consumption survey was conducted to patients with inflammatory arthritis treated at the department of Rheumatology. Variables assessed: demographics, diagnosis, treatment, and current smoking. In smokers and former smokers patients: onset age of smoking, number of cigarettes per day, time exposure to tobacco and if they were active smokers before the diagnosis of their disease. All patients were also asked if received information about tobacco as a risk factor for inflammatory disease; and current to the active smokers if they wanted to stop. Awareness activities against tobacco were conducted. RESULTS: Patients were included 198. The most prevalent diagnosis was rheumatoid arthritis (58.1%). Most patients were treated with biological therapy. Fifty percent of patients were non-smokers, 31% former smokers and 19% active smokers. Ninety-two percent of smokers and 89% former smokers already smoked before diagnosis of the disease. Thirty-five percent of all patients had received information about the risks of tobacco. Eighty percent of current smokers wanted to stop smoking. CONCLUSIONS: Active smoking was reported in 19% of patients with inflammatory arthropathies visited in our Arthritis. Department patients were willing to receive tobacco education. These results indicate the need to provide advice against tobacco in a systematic and structured manner. PMID- 26540895 TI - [EMOTIONAL MANAGEMENT AND CRITICAL THINKING IN THE AID RELATIONSHIP OF THE HOLISTIC CARE OF PALLIATIVE PATIENTS]. AB - To care for palliative patients is essential that healthcare professionals develop emotional competencies. This means acquiring the habit of self reflection and be emphatic with other people, in order to be able to identify the personal emotions of patients, family and team. Reflection involves a continuing effort to reason about aspects of professional practice, especially on issues as complex as suffering and death. Both reflective reasoning and emotional management are vital in an Aid Relationship. For nursing healthcare professionals, to care the emotional aspects means becoming aware of their own and others feelings, and get to understand and accept to handle them properly. Nursing actions involves many qualities of social competence, such as empathy, understanding, communication skills, honesty, flexibility and adaptability to the individual needs of people cared. In the context of palliative care patients and their families all these aspects are fundamental and are part of the same philosophy. Emotional education still remains a challenge in our profession both in the initial and continuing training. PMID- 26540896 TI - [GENERIC DRUGS: IS BIOEQUIVALENCE SUFFICIENT TO ENSURE QUALITY, EFFICACY AND SAFETY?]. AB - This article is focusing on the current debate that prescription of generic drugs is producing among patients and healthcare professionals. Following European Medicine Agency (EMA) recommendations, a number of generic medicines have recently been withdrawn from the market in Spain. The authorization for these generic drugs was primarily based on clinical studies conducted at GVK Biosciences in Hyderabad, India. The EMA inspection of GVK revealed data manipulation of electrocardiograms during the development of some studies of generic medicines. These manipulations had taken place over a period of at least five years. The article is also dealing with the consideration that bioavailability and bioequivalence studies receive as a cornerstone to approve generic drugs, and the discrepancies between the national regulatory agencies of medicines to implement guidelines of approval. Likewise, in the last few years, the rapid expansion of clinical trial activity regarding generic medicines and other drugs in emerging markets, is often leading to doubt on the integrity of the way trials were performed and on the reliability of data obtained from these studies. PMID- 26540897 TI - [AN EDUCATIONAL EXPERIENCE BASED ON CLICKERS]. AB - Active learning or self-learning increases the student's participation and commitment to his studies; these conditions are necessary to improve academic performance. An intervention has been designed based on the experience in the use of clickers in other universities, but without the actual technology. This work has been performed in the School of Nursing affiliated to the University of Malaga (UMA) on students enrolled in their second year of Degree in Adult Nursing Course I. Three sessions of multiple-choice questions were scheduled on the subject "distance learning" in which master classes were not taught. The answers were collected on paper templates. We wanted to determine the degree of relationship between the attendance of sessions and the results obtained by students in the final examination of the subject, as well as, the questions dedicated to assess the "distance learning" matter. The results support a significant statistical difference in the correct answers by students according to the number of sessions attended. These differences are highest among students who did not attend any session and those who attended the three planned sessions. PMID- 26540898 TI - [LOXOCELES BITE WOUND TREATMENT WITH SYNTHETIC POLYMER MATRIX]. AB - Loxocelism is a toxic condition produces by the venom inoculated by the bit of the recluse spider (genus Loxosceles). In can appear in two clinical forms: cutaneous loxocelism and viscerocutaneous Ioxocelim. The species Loxoceles rufescens, found in Spain, is responsible of cases of cutaneous loxocelism. Cutaneous loxocelism starts with an itch, later giving rise to intense pain, and it later takes either a more or less severe necrotic form or an edematous form. The latter, with a better prognosis, is the one we focus on here. The diagnosis is clinical. The systemic treatment consists in analgesics, antihistamines, corticosteroids, broad-spectrum antibiotics, and dapsone in severe cases. The local treatment is based on the cleaning and debridement of the wound, and in advanced treatments for complex wounds. It is not uncommon that such wounds require skin grafting. We present the case of an 18-year female bitten by a loxosceles on the dorsal area of the foot. She developed a deep tissue necrosis in the area. She presented systemic complications such as leucocitosis, fever, local infection and cellulitis. Systemic treatment and hospitalization were required, as well as advanced therapeutic care. Finally, cutaneous integrity was restored after 84 days. PMID- 26540899 TI - [Celebration of the World Day of Endometriosis]. PMID- 26540900 TI - [XV Conference on Ethics "Ethics Issues in Pediatrics"]. PMID- 26540901 TI - [First edition of nursing award 2014 on applications of a synthetic matrix of polymers powder formulated for wound healing]. PMID- 26540902 TI - [Nursing advocates the prevention of pressure ulcers]. PMID- 26540903 TI - [University postgraduate education in nursing]. PMID- 26540905 TI - [DRAINAGE OF POSTOPERATIVE SEROMA IN BREAST SURGERY WITH SEROMASET]. AB - Breast cancer is the most common malignancy in women. The surgical approach is one of the cornerstones in the treatment of this disease. One of the complications of surgery is postoperative seroma. Despite not being a serious complication, for women it is, and involves discomfort, more hospital visits and sometimes delay of adjuvants treatments. PMID- 26540904 TI - [THE IMPORTANCE OF PROPER ADHERENCE TO ANTI-TUBERCULOSIS TREATMENT]. AB - INTRODUCTION: Tuberculosis (TB) remains a major cause of morbidity and mortality in many countries. This involves a serious public health problem. Adherence to TB treatment is a cornerstone for the control of this disease. DEVELOPMENT: Globally, there are major differences between countries as to the prevalence, incidence and mortality tuberculosis. Spain has a incidence rate higher than that of other countries in their socio-economic background. Treatment is prolonged, with significant side effects. Adherence to treatment is essential to be effective, prevent drug resistance and disease control. Children are more vulnerable to developing the disease than the rest of the population. Several direct and indirect methods measure the adherence to treatment, but none is ideal. Some socio-demographic risk factors that influence on adherence are described (immigration...). In addition, there are another more specific child factors to have been add. CONCLUSIONS: The literature reviewed highlights the importance of proper monitoring of patients to increase adherence to TB treatment. The role of the nurse and their interventions are very important. PMID- 26540906 TI - [SUPPORT TO FAMILIES OF CRITICALLY ILL PATIENTS]. AB - INTRODUCTION: The hospitalization of the sick person in the family creates anxiety, stress, etc... The families in this situation have no tools to face reality and ignore their needs. OBJECTIVE: To identify the relationship between family needs and nursing interventions. METHODS: We conducted a literature review in the databases Pub-Med, CINAHL, Cuidatge, Cuiden and ScienceDirect. After including items that meet the selection criteria were selected 18 items RESULTS AND DISCUSSION: In selected items were analyzed the necessities generated by the hospitalization of a family member in the ICU, performances, interventions and proposals for improvement that are proposed to meet the needs and constraints and reluctance that occur in practice. CONCLUSIONS: Although the literature identifies the needs of the family, the problems encountered and solutions proposed, the nurses do not integrate these needs into their operations. PMID- 26540907 TI - [EVALUATION OF THE EFFICIENCY OF CLEANING THE AIR BETWEEN TWO METHODS OF MAKING IN PATIENTS WITH AEROSOL CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. AB - INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a condition which requires, among others, the administration of bronchodilators and anti inflammatory drugs to control the disease. They help to keep the airways clear and prevent the buildup of fluid and mucus. Inhalation is the most widely used form of administrating the medication because of its local and rapid action which normally is done by aerosol therapy. The objective of this study is to evaluate the effectiveness of two aerosol methods in clearing the airways of COPD patients, admitted with an exacerbation due to their disease. It also aims to evaluate its effects on the length of stay, oxygen saturation, dyspnea, autonomy and complications. METHODS: Randomized clinical trial. Traditional method (control group) and positive expiratory vibrating device (intervention group): two ways to deliver aerosol were compared. The following outcome variables were considered: length of stay, days of fever, oxygen saturation, need for NIV or VM, the basic activities of daily living index autonomy (Barthel), dyspnea (Borg scale) and peak-flow. RESULTS: 39 patients were included. Regarding hospital stay, patients in the intervention group spend an average of one day less in hospital. Also in this group there were fewer readmissions. No statistically significant differences were found in the remaining variables. CONCLUSIONS: The inhalation treatment with a vibrating device with positive exhalation, appears to reduce the length of stay and prevent readmissions. It is important to continue research on non-pharmacological interventions as to achieve the prevention of relapses. PMID- 26540908 TI - [NURSING PROFESSIONALS: EXISTENCE OR NON-GENDER BIAS AND ITS IMPACT ON THE HEALTH OF WOMEN]. AB - The aim of this article is known through literature review the existence or absence of gender bias in the exercise of the nursing profession in two specific problems such as cardiovascular disease (CVD) and panic attacks. We want to know how these biases might be impacting clinical diagnosis and health care received by men and women. A search was performed in Medline, Psicodoc, Psycinfo and Cuiden under keywords: "gender bias", "gender differences", "nursing", "healthcare", acardiovascular disease), "anxiety", selected from a total of25 items are allowed to offer a global view on possibles gender bias in the performance of the health professions in the two pathology understudy PMID- 26540909 TI - [PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT]. AB - OBJECTVE: To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. METHODOLOGY: Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. RESULTS: The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. DISCUSSION: Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm PMID- 26540910 TI - [The study of siRNA interference after laryngeal cancer Hep-2 cells to cisplatin sensitivity of beta-catenin gene expression]. AB - OBJECTIVE: To investigate the changes of laryngeal cancer Hep-2 cells to cisplatin chemosensitivity after the interference of siRNA of beta-catenin gene expression. METHOD: Using a small interference RNA (siRNA) technology interfere beta-catenin gene of Hep-2 cells . The mRNA and protein levels of beta-catenin in the Hep-2 cells of different groups were detected by qPCR and Western blot. It was divided into siRNA-beta-catenin-Hep-2 siRNA group, beta-catenin-Neg negative control group and blank control group. Cell proliferation inhibition rate of different concentrations of cisplatin on three groups was detected by MTT assay. Calculate the 50% inhibitory effective concentration IC50 value. Check the change of three groups of cells' apoptosis rate by flow cytometry after the same concentrations of cisplatin stimulation. RESULT: beta-catenin-siRNA interference fragment can specifically reduce the expression levels of beta-catenin mRNA and protein. qPCR illustrated the expression of mRNA in beta-catenin-siR-NA-Hep-2 interference group decreased 70% (P < 0.05) compared with the control group, Western blot results showed that the beta-catenin protein expression of interference group (0. 545 +/- 0.111) decreased significantly compared with blank control group (1.507 +/- 0.139) and negative control group (1.429 +/- 0.089), P < 0.05. The IC50 calculation software showed that IC50 of cisplatin on beta-catenin siRNA IC50 interference group is (5.81 +/- 0.46)MUg/ml, the blank control group is (10.10 +/- 1.01) MUg/ml, the difference between the two groups has statistical signifi- cance (P < 0.01). Cell apoptosis rate of beta-catenin-siRNA interference group was (26.15 +/- 0.60)%, significantly higher than the control group (14.16 +/- 0.05)%, P < 0.05. CONCLUSION: To interfere the expression of beta-catenin can effectively enhance the sensitivity of laryngeal cancer cells to chemotherapeutic drugs cisplatin. It provides a theoretical support for the reduction of laryngeal cancer chemotherapy drug cisplatin dosage. PMID- 26540911 TI - [The expression of Nrf2 and Keap1 in laryngeal carcinoma and its clinical indication]. AB - OBJECTIVE: To investigate the role of Keap1-Nrf2-ARE pathway in laryngeal carcinoma occurrence and development. METHOD: Thirty-five laryngeal carcinoma samples and para-carcinoma tissues were taken from the patients who accepted operation treatment in our hospital from Feb 2012 to Sep 2013. The expression levels of Nrf2 and Keap1 were detected in 35 cases of laryngeal carcinoma with SP immunohistochemical methods. The data were analyzed by the SPSS 13.0 statistical software. RESULT: The expression of Nrf2 in the 35 cases of laryngeal carcinoma was 77.14%, which in the para-carcinoma tissues was 8.57%, the difference between these two groups was statistically significant (P < 0.01). The expression of Keap1 in the 35 cases of laryngeal carcinoma was 71.43%, which in the para carcinoma tissues was 31.43%, the difference between these two groups was statistically significant (P < 0.01). The expression of Nrf2 in I -II stage was 65.00% and in III-IV stage was 93.33%, the difference was significant (P < 0.05). The expression of Keap1 in I-II stage was 55.00% and in III-IV stage was 93.33%, the difference was significant (P < 0.05). Of the 35 cases, the positive expression rate of Nrf2 and Keap1 in laryngeal carcinoma with lymphnode metastasis were both 100.00%, compared with those without lymph nodes metastasis 68.00% and 60.00%, the difference was significant (P < 0.05). The expression of Nrf2 and Keap1 had no relationship with tumor differentiation, smoking and patient age (P > 0.05). CONCLUSION: Keap1-Nrf2-ARE pathway may play an important role in progression of laryngeal squamous cell carcinoma. PMID- 26540912 TI - [The expression of PKM2 and HIF-1alpha in laryngeal squamous cell carcinoma and its clinical indication]. AB - OBJECTIVE: The purpose of this study was to investigate the expression of PKM2 and HIF-1alpha in laryngeal squamous cell carcinoma and to analyze their correlation in laryngeal squamous cell carcinoma. METHOD: Total 37 laryngeal carcinoma samples and para-carcinoma tissues were taken from the patients who accepted operation treatment in the Second Hospital of HeBei Medical University from 06/2013 to 06/2014. The protein expression levels of PKM2 and HIF-1alpha were detected with SP immunohistochemical methods. The data were analyzed by the SPSS 13.0 statistical software. RESULT: The positive expression of PKM2 in laryngeal carcinoma tissues and adjacent tissues were 62.16% and 13.15%. The difference was statistically significant (P < 0.01). The positive expression of HIF-1alpha in laryngeal carcinoma tissues and adjacent tissues were 64.86% and 21.62%. The difference was statistically significant (P < 0.01). The positive expression of PKM2 and HIF-1alpha in well differentiated laryngeal squamous cell carcinoma were both 47.83%, while in medium and poorly differentiated laryngeal squamous cell carcinoma were 85.71% and 92.86% respectively. The difference was statistically significant (P < 0.05). The positive expression of PKM2 and HIF 1alpha in patients with lymph metastasis were 90.00% and 100.00% respectively, 51.85% in those without lymph metastasis, the difference was statistically significant (P < 0.05). The rate of HIF-1alpha positive expression in I-II stage was 53.85%, 90.91% in III-IV stage. The difference between the two groups was statistically significant (P < 0.05). The expression of PKM2 and HIF-1alpha had no relationship with the age and smoking (P > 0.05). The expression of PKM2 was positively related with HIF-1alpha in laryngeal squamous cell carcinoma (P < 0.01). CONCLUSION: The expression of PKM2 and HIF-1alpha are related with the proliferation, invasion and metastasis of laryngeal squamous cell carcinoma. It provides a certain theoretical basis for laryngeal cancer diagnosis and screening to measure the expression of PKM2 and HIF-1alpha as biological indicators. PMID- 26540913 TI - [The expression of Endophilin II and VEGF-C in human laryngeal cancer and connection with clinical treatment]. AB - OBJECTIVE: To study the expression of Endophilin II and VEGF-C in human Laryngeal cancer and its relationship with the clinical treatment effect. METHOD: The expression and distribution of Endophilin II and VEGF-C protein were checked in 47 patients with laryngeal carcinoma in our hospital in 2006-09-2009-10 and 23 samples of normal tissues around the cancer by immunohistochemical staining SP method. After an appropriate surgical treatment, patients accepted a 5-year followup to evaluate their recurrence situation and 5-year survival rate. RESULT: Immunohistochemistry showed that Endophilin II protein was strongly positive expressed in normal tissues around the cancer (positive rate 82.61%). And the expression level was dependent on the lymph metastasis, T stage and lymph invasion (P < 0.05). Patients with positive Endophilin II expression had a higher survival rate and better recurrence situation. Expression of VEGF-C was significantly higher in laryngeal carcinoma than in normal tissue around the cancer (positive rate 51.06% and 13.04%). the expression level was dependent on the lymph metastasis and lymph invasion (P < 0.05), and negatively correlated with recurrence and 5-year survival rate. CONCLUSION: Endophilin II and VEGF-C may involve in laryngeal cancer, and the expression of Endophilin II and VEGF-C has a positive correlation with pathological features and lymph metastasis, and both are related with recurrence and 5-year survival rate. So these two proteins are likely to be a potential target for diagnosis and treatment of laryngeal cancer. PMID- 26540914 TI - [Relationship of local recurrence with the expression of Survivin and MMP-2 in laryngeal carcinoma and its surgical margins]. AB - OBJECTIVE: To explore the relationship of the local recurrence with the expression of protein Survivin and MMP-2 in the primary lesions and the surgical margins of laryngeal carcinoma. METHOD: The primary lesions and the surgical margins of laryngeal carcinoma of 48 patients were made into serial sections. Immunochemical methods was used to detect the expression of protein Survivin and MMP-2 in the primary lesion and the surgical margins of laryngeal carcinoma of 48 patients. RESULT: The positive expression for Survivin and MMP-2 in the primary lesion was 70.83% (34/48) and 66.67% (32/48) respectively, and the positive expression of Survivin and MMP-2 in the surgical margins of laryngeal carcinoma was 47.92% (23/48) and 37.50% (18/48), which in the primary lesion was significantly higher than those of the surgical margins of laryngeal carcinoma (P < 0.05). The recurrence rates of primary lesion positive for Survivin (34 cases) and MMP-2 (32 cases) were 26.47% (9/34) and 25.00% (8/32), which were higher than negative for them 7.14%(1/14) and 12.50% (2/16) (P > 0.05). The recurrence rates of those with Survivin (23 cases) and MMP-2 (18 cases) positive surgical margins were 34.78% (8/23) and 38.89% (7/18) respectively, which were significantly higher than those with negative ones 8.00% (2/25) and 10.00% (3/30) (P < 0.05). Logistic analysis showed that the expression of Survivin and MMP-2 protein in the surgical margins of laryngeal carcinoma was positively associated with the recurrence rates. CONCLUSION: Laryngeal carcinoma patients with Survivin-positive or MMP-2-positive margin would have a higher recurrence rate. Survivin and MMP-2 protein can be used as biomarkers for local recurrence of laryngeal carcinoma after operation. PMID- 26540915 TI - [The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing]. AB - OBJECTIVE: To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing. METHOD: We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism. RESULT: Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism. CONCLUSION: The probability of hereditary hearing loss is 7.09% in newborn with GJB2 heterozygous mutation in Beijing. It is noteworthy that c. 109G>A, c. 368C>A occupy a high proportion. PMID- 26540916 TI - [The development of vocabulary capability at 2-year follow-up in the prelingual deaf children with cochlear implants]. AB - OBJECTIVE: To investigate the development of early vocabulary capability in the prelingual deaf children after cochlear implantation (CI) , and to study the feasibility of current Chinese assessment procedures about language development for hearing-impaired children. METHOD: A total of 56 cases with severe-to profound prelingual deaf children were participated in this study. The vocabulary development of CI children were evaluated by trained audiologists using the vocabulary assessment tools: Chinese communicative development inventory (CCDI) and mandarin expressive and receptive vocabulary test (MERVT). The questionnaire assessed by parents or guardians answered the questionnaire; vocabulary tests were evaluated by children accompanied with audiologists. Patients were assessed before operation and in 2 years after switch-on. RESULT: With the rehabilitation, early post-operative vocabulary development gradually improved. The vocabulary increased with an increase in the duration of CI use, and the receptive vocabulary developed earlier than the expressive ones. CONCLUSION: After 2 years of CI use, the child partly developed the vocabulary capability. Children's vocabulary test, CCDI and MERVT test, is an important index to evaluate the development of children's language ability after cochlear implantation. Vocabulary test, together with auditory and speech perception assessment procedures, constitute a more complete auditory-speech-language evaluation system for Chinese children after cochlear implants. PMID- 26540917 TI - [The research of rehabilitation effect of cochlear implantation for deaf children with gene mutation]. AB - OBJECTIVE: To assess the evaluation on auditory rehabilitation effect for 42 deaf children with GJB2 gene mutation after cochlear implantation to provide a reference for the cochlear implant effect evaluation of such patients. METHOD: To conduct the detection on common genetic deafness gene mutation hotspots of hearing impaired children with cochlear implantation. To conduct auditory rehabilitation effect evaluation on 42 cases of patients with GJB2 genetic deafness after 3 months, 6 months and 12 months of the operation respectively. The single factor repeated measure ANOVA was applied to analyze whether there were significant difference among the results of initial consonant of a Chinese syllable recognition at 3 different stages after the operation, the results of vowel of a Chinese syllable recognition at 3 different stages after the operation, and the results of two-syllable recognition at 3 different stages after the operation. RESULT: 235delC is the high-incidence mutational site in 42 cases of patients with GJB2 genetic deafness, the total detection rate is up to 90.48%. There were significant differences in the initial consonant of a Chinese syllable recognition rate, the vowel of a Chinese syllable recognition rate, the two-syllable recognition rate as well as the vowel of a Chinese syllable recognition rate after 3 months, 6 months and 12 months of the operation (P < 0.01). CONCLUSION: Cochlear implantation is a safe and effective measure for auditory reconstruction, it can help patients with GJB2 hereditary severe sensorineural deafness to improve auditory speech recognition. PMID- 26540918 TI - [Cervical vestibular evoked myogenic potential elicited by different types air conducted sounds among normal young Chinese people]. AB - OBJECTIVE: To observe waveform difference among cervical vestibular evoked myogenic potentials (cVEMP) elicited with different types of air conducted sound in normal young Chinese subjects. METHOD: Twenty adult volunteers (40 ears) were recruited as research subjects including 10 males and 10 females aged between 19 and 30.500 Hz Tone Burst, 1000 Hz Tone Burst and Click were employed as stimulus for conventional air conducted sound-cVEMP (ACS-cVEMP) examinations in bilateral ears of each subject. The response rate, threshold, P1 latency, N1 latency, P1-N1 latency interval, amplitude and inter-aural asymmetry were recorded and compared among groups. RESULT: The response rate was 97.5% in 500Hz Tone Burst (39/40), 87.5% in 1 000Hz Tone Burst (35/40)and 67.5% in Click (27/40), There were no statistically significant difference between 500Hz Tone Burst and 1000Hz Tone Burst (P > 0.05) but there were statistically significant difference between click and the other groups (P < 0.05). We collected the waveform parameters (the threshold, P1 latency, N1 latency, P1-N1 latency interval, amplitude) which had statistically significant difference between 500 Hz Tone Burst and the other groups (P < 0.05). The inter-aural asymmetrys had no statistically significant differents among groups. CONCLUSION: The response rate and parameter could be affected by different types of air conducted sound in normal young Chinese subjects. 500 Hz Tone Burst was the best stimulus of type what we have known. PMID- 26540919 TI - [Activation of mTOR signaling pathway in cancer stem cells of nasopharyngeal carcinoma and inhibitive effect of rapamycin against the cancer stem cells]. AB - OBJECTIVE: To study the mTOR expression of cancer stem cells(CSCs) in nasopharyngeal carcinoma and preliminarily explore the mechanism of inhibiting its proliferation with rapamycin. METHOD: Nasopharyngeal carcinoma spherical cells were gathered by using serum-free suspension culture method, CCK8 assay was used to detect cell proliferation, Western blot assay was used to detect the expression of CD44, OCT4, SOX2 and mTOR signaling. The spherical cells and CNE2 were treated with rapamycin in concentrations of 0, 0.1, 1.0, 10.0, 100.0, 1000.0 nmol/L, CCK8 assay was used to detect cell inhibition ratio, Western blot assay was used to detect the expression of mTOR signaling of nasopharyngeal carcinoma spherical cells. RESULT: Compared with CNE2, the spherical cells exhibited a high proliferation rate in RPMI 1640 medium supplemented with fetal bovine serum, and overexpressed in OCT4, SOX2 (P < 0.05), but not that of CD44 (P > 0.05). Although the expression levels of mTOR, P70S6, 4EBP1 were not significantly different between the two kinds of cells (P > 0.05) the proteins of phosphorylation activation form of them (P-mTOR, P-P70S6, P-4EBP1) were highly expressed in spherical cells (P < 0.05). The spherical cells and CNE2 were treated with rapamycin in different concentrations, the concentrations for 50% of maximal effect of spherical cells and CNE2 were 2.59 nmol/L and 78.12 nmol/L respectively, rapamycin inhibited the spherical cells more strongly compared with CNEZ. The expression levels of P-mTOR, P-70S6, P-4EBP1 in spherical cells were gradually decreased with increasing of the concentrations of rapamycin, but the difference of the expression levels of mTOR, P70S6, 4EBP1 were not significant. CONCLUSION: The proteins of mTOR signaling pathway of CSCs in nasopharyngeal carcinoma are overexpressed, and rapamycin can effectively inhibit cell proliferation of CSCs in nasopharyngeal carcinoma by blocking mTOR signaling pathway. PMID- 26540920 TI - [Expressions of Maspin and Ki67 in extranodal nasal type NK/T-cell lymphoma and the significance]. AB - OBJECTIVE: To analyze the expression of Maspin and Ki67 in EN-NK/TCL and the significance. METHOD: The expressions of Maspin and Ki67 were detected by immunohistochemistry in 34 cases of EN-NK/TCL and 11 cases of chronic sinusitis. RESULT: Maspin was low expressed in EN-NK/TCL, Ki67 was highly expressed in EN NK/TCL. Negative correlation was found between the expression of Maspin and Ki67 in EN-NK/TCL. CONCLUSION: The combined examination of Maspin and Ki67 has important significance in the diagnosis in EN-NK/ TCL. PMID- 26540921 TI - [A clinical study of 27 cases of cervical metastatic carcinoma of unknown primary site]. AB - OBJECTIVE: To analyze the clinical feature of cervical metastatic carcinoma of unknown primary site (CCUP) for guiding clinical diagnosis and treatment. METHOD: Twenty-seven cases of CCUP during May 2007 to September 2013 in department were analyzed retrospectively. Kaplan-Meier method and Log-rank test were used for survival analysis, multivariate analysis using the Cox regression model. RESULT: There is no significant influence among gender, age and the mass position on the median survival time. Median survival time of patients with different pathological types was statistically significant (P < 0.05). Treatment affected the median surial significantly (P < 0.05) and also was the independent prognostic factors (P < 0.05). CONCLUSION: The early establishment of pathological type and primary focal position can improve the prognosis. Taking treatment according to pathological types can increase the patient's survival rate. Combined treatment can prolong the patient's survival time. PMID- 26540922 TI - [The surgical options of cervical tuberculous lymphadenitis]. AB - OBJECTIVE: To analyze the clinical features & variation features of cervical tuberculous lymphadenitis and to discuss its effective surgical treatment. METHOD: Retrospective analysis of 27 cases of cervical tuberculous lymphadenitis patients admitted to the hospital from January 2008 to December 2013. The cervical tuberculous lymphadenitis is classified based on the enhanced CT scanning conducted before operation and the preoperative evaluation of clinical characters of patients. The lymphaden ncisional biopsy was conducted on the type I patients with cervical tuberculous lymphadenitis. The lesion resection was performed on the type II and mixed type I + II patients. The regional cervical lymph node dissection was carried on the type III, the type IV and other mixed type patients. The negative pressure drainage ball was placed after operation, and the cavity was flushed with 5% povidone iodine solution. The antituberculosis therapy was performed after wound healing. RESULT: The analysis of the clinical features for 27 patients: the incidence rate on the left side, right side, both sides and middle-line is 63.0%, 25.9%, 7.4% and 3.7% respectively. The majority of patients whose lesion involving more than one region account for 62.1%; the patients whose lesion involving one region account for 37.9%. The most common is level V involved lesion (69.0%), then level IV (62.1%), level III (51.7%), level II (34.5%), level I (10.3%) and level VI (3.4%) in order. The analysis of the CT imageology features for 27 patients: the simple type is the majority (65.5%), and the most common is type III (24.1%), then the type I (17.2%), type II (13.8%) and type IV (10.3%) in order. The mixed type is minority (34.5%), but the two mixed is often (31.0%). The three mixed is only located on one side (3.4%). The recurrence never happened on the patients with resection and standard antituberculosis therapy. CONCLUSION: For the cervical tuberculous lymphadenitis, the suitable surgical treatments shall be selected according to the lesion characteristics & location and CT imaging manifestations presurgical evaluation. The effective way to treat cervical tuberculous lymphadenitis is to conduct negative pressure drainage after operation, to flush the cavity with 5% povidone iodine solution and to perform antituberculosis therapy. PMID- 26540923 TI - [The effect of TFF3 on the proliferation and migration of papillary thyroid carcinoma K1 cell]. AB - OBJECTIVE: To explore the effect on proliferation and invasion of human papillary thyroid carcinoma K1 cells by application of small hairpin RNA (shRNA) silencing TFF3 gene expression. METHOD: Using liposome transfection method, TFF3-shRNA targeting of TFF3 gene will be transient transfected to papillary thyroid carcinama K1 cells, inducing the corresponding gene silencing. The experiment set up blank control group (Con group), negative control group (ConNC group) and interference group (TFF3-shRNA group). The TFF3 protein and mRNA expression were evaluated by RT-PCR, Real time-PCR, immunocytochemistry and Western blot in K1 cells after TFF3-shRNA transfected. CCK-8 method and Scratch test were used to detect the change of proliferation ability and invasion ability respectively. RESULT: (1) The recombinant plasmid Ca # HSH018037-4-HIVmU6 carrying TFF3-shRNA transfected K1 cells successfully. (2) RT-PCR and Real time-PCR detected the expression of TFF3 mRNA, which was 0.38 +/- 0.11 times as many as the blank control group (P < 0.01) after TFF3 gene silenced. But the negative control group was 1.082 times of blank control group (P > 0.05). (3) Western blot show that after TFF3 gene silence induced TFF3 protein expression levels have decreased 59.5% (P < 0.01), The difference was statistically significant compared with the blank control group. (4) Cell scratch detects K1 cell invasion ability. The invasion ability of K1 cells in interference group (TFF3-shRNA group) reduced. The scratch width significantly decreased 57.1% than blank control group (P < 0.01). (5) CCK-8 kit detect cell proliferation ability. K1 cells grow significantly slower in the interference group (TFF3-shRNA group) than the blank control group through the analysis of the growth curve (P < 0.01). In the interference group (TFF3-shRNA group) proliferation inhibition rate of K1 cells at 6 h, 12 h, 24 h and 36 h, 48 h are 16.6%, 26.6%, 33.6%, 33.8%, 35.0% respectively. Compared with negative control group, proliferation ability of K1 cell decreased significantly. CONCLUSION: Silenced TFF3 gene can cause the degradation of mRNA, reduce the protein translation , and inhibit the invasion and proliferation ability of K1 cell. PMID- 26540924 TI - [Clinical application of cone-beam CT online correcting technology in volume modulated radiation therapy for nasopharyngeal carcinoma]. AB - OBJECTIVE: To investigate the clinical application value of cone-beam CT (CBCT) online correcting technology in volume modulated radiation therapy (VMRT) for nasopharyngeal carcinoma (NPC). METHOD: Fifty NPC patients applying head neck and shoulder thermoplastic body membrane fixing device were eligible for treatment VMRT, these patients would accept a couple of CBCT scanning by on board imager (OBI) in a fixed time each week after initial setup and after online correcting during the first three week for radiotherapy, CBCT images and DRR images constructed by CT simulation were carried out registration,which could calculate the setup errors of initial setup and after online correcting. RESULT: Fifty patients were accepted 150 scanning after initial setup and 150 scanning after online correcting respectively, the errors after initial setup were (-1.24 +/- 1.25)mm in X direction, (1.19 +/- 1.85)mm in Y direction, (1.49 +/- 1.70) mm in Z direction. The setup errors after online correcting were (-0.13 +/- 0.29)mm in X direction, (0.10 +/- 0.47)mm in Y direction, (0.17 +/- 0.36)mm in Z direction. The setup errors after online correcting were significantly lower than the errors after initial setup in X direction (P < 0.05), Y direction (P < 0.05), Z direction(P < 0.05). The M(PTV) value after online correcting were 0.46 mm, 0.53 mm and 0.59 mm in X, Y and Z directions respectively. CONCLUSION: The use of CBCT online correcting technology can significantly reduce the setup errors of VMRT for NPC and improve the treatment effect. PMID- 26540925 TI - [Analysis on allergen of clinical allergic rhinitis patients in north-west mountain area of Hubei Province]. AB - OBJECTIVE: To investigate the main inhaled allergens and the difference of that between city and rural suburbs in patients with allergic rhinitis in the mountain region of the northwest Hubei province and to provide epidemiological basis for prevention and treatment in the region. METHOD: Eight hundred and thirty-five cases who were diagnosed as allergic rhinitis with standardized allergens in Taihe Hospital of Hubei University of Medicine from Sep 2009 and Dec 2011 were studied. The data of allergens and the distribution of the patients were recorded and analyzed. chi2-test were used to analyze the data. RESULT: The top 7 of inhaled allergens were house dust mites (89.6%), dust mites (86.0%), tropical mites (56.9%), croton bug (18.8%), felon herb (8.1%), the cat hair (8.1%) and fine chain alternata bacteria (9.5%), Two main kinds of allergen in three different area are with no obvious difference (P > 0.05). CONCLUSION: In northwest Hubei Province, the highest rate of inhaled allergens was dust mites, which are approximate in different age groups and different regions, especially in the city. PMID- 26540926 TI - [Study on the correlation between the severity of chronic rhinosinusitis and bronchial asthma and pulmonary function]. AB - OBJECTIVE: To explore the correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the pulmonary function. METHOD: Sixty-four cases of patients with rhinitis-nasosinusitis and 53 cases of patients with chronic sinusitis from June 2012 to September 2013 were randomly selected, and the patients were divided into group of rhinitis-nasosinusitis with nasal polyps and group of chronic sinusitis according to disease species, and analyzed the correlation between the severity of the deseases and the changes of the pulmonary function respectively for the patients of two groups by using Spearman method. RESULT: The incidence of asthma for patients with different levels of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant difference (P > 0.05); the incidence of asthma for patients with different lesion range of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant different (P < 0.05). The conditions of the patients with different levels of sinusitis and nasal polyps were directly related to the reduction of pulmonary function (r = 2.431, P < 0.05); The conditions of the patients with different lesion range of sinusitis were directly related to the reduction of pulmonary function (r = 2.641, P < 0.05). CONCLUSION: There was some correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the condition of pulmonary function of patients. PMID- 26540927 TI - [Application of philosophy on comprehensive analysis of adenoid hypertrophy space occupying effect in meticulous adenoidectomy]. AB - OBJECTIVE: To achieve targeted and meticulous surgery of adenoid hypertrophy, a comprehensive analysis of adenoid hypertrophy space occupying effect and morphological evaluation were conducted and the clinical results were retrospectively analyzed. METHOD: One hundred and sixty-three children with adenoid hypertrophy were treated in our department from May 2013 to May 2014. All children received three examinations preoperatively, including: Nasopharyngo fiberoscopy, Audiometry and Tympanometry. Based on the results, space occupying effect of adenoid hypertrophy was divided into three types: vertical hypertrophy type, horizontal hypertrophy type and vertical & horizontal hypertrophy type. We assumed the causal relationship with vertical hypertrophy type to snoring (nasal blockage) and horizontal hypertrophy type to secretory otitis media respectively. All children received transoral endoscopic adenoidectomy with radiofrequency ablation. RESULT: The postoperative followup of these children for 6 to 12 months showed that the vertical hypertrophy type and horizontal hypertrophy type children all recovered from the syndromes of snoring (nasal blockage) and secretory otitis media respectively. The nasopharyngo-fiberoscopy showed that the nasopharyngeal space was smooth and the bilateral choanas opened well. No recurrence was found. CONCLUSION: The philosophy of comprehensive analysis on adenoid hypertrophy space occupying effect could help the surgeons understand adenoid hypertrophy better and can guide the adenoidectomy more meticulously. PMID- 26540928 TI - [Radiation injury of interstitial implantation 125I seeds on normal trachea tissue of rabbits]. AB - OBJECTIVE: To study the radition injury of tracheal mucous membrane tissue after interstitial implanted radioactive 125I in normal rabbit,improve the safety of clinical application. METHOD: Sixty New Zealand rabbits, weighing 2.15-2.30 kg, were randomly divided into 1 w, 1 m, 2 m, 4 m and the control group, the control group was further divided into four subgroups. The 0.8mCi 125I seeds were implanted into the tissue by the first tracheal ring in the treatment groups and nonradioactive seeds were implanted in the control group. Taking the tracheal mucous membrane tissue for pathological examination by HE staining to observe the mucosal injury and VEGF, Pan-Cadherin immunohistochemical staining to observe the expression in differernt time. RESULT: Immunohistochemical staining: VEGF and Pan Cadherin have statistically significant differences in the expression on different time, the expression is dynamic. CONCLUSION: The expression of VEGF and Pan-Cadherin reflect the radioactive 125I seed has little influence on normal trachea tissue and the damage can be repaired by the regeneration of the basal cell. PMID- 26540929 TI - [Effect of sildenafil on morphology to noise-induced hearing loss in guinea pigs]. AB - OBJECTIVE: To study the effects of sildenafil on morphology to noise-induced hearing loss in guinea pigs. METHOD: Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, 12 in each group. a week after white noise exposure of 110 dB, sildenafil (10 mg/kg x d) and NS (4 ml/kg x d) were injected into guinea pigs of the sildenafil treatment group and noise exposure group respectively for four continuous weeks. ABR thresholds were measured respectively prior to the experiment, 1 week post noise, 1, 2 and 4 weeks post-drugs, the changes of cochlea hair cells were also observed with a scan electron microscope (SEM) and light microscope. RESULT: The ABR threshold shifts in the sildenafil treatment group were significantly fewer than that in the noise exposure group. SEM showed that hear hair of the inner and outer hair cells in noise exposure group displayed mess, fusion and imperfections. In the sildenafil treatment group, the hair cells displayed slight pathological changes, there wasn't significant differents comparied with normal group. The number of OHCs were relatively stable in the normal group, while the obvious OHC loss was observed in other groups. There was significant difference among the three groups, however, the OHC loss in the sildenafil treatment group was not significantly different to that in the noise exposure (P > 0.05). CONCLUSION: Sildenafil can significantly protect against noise-induced hearing loss. PMID- 26540930 TI - [Alveolar soft part sarcoma of the larynx: a case report]. AB - Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcomas, this sarcoma occurs rarely in the larynx. Herein, we describe an unusual case of ASPS occurring in the larynx. The patient was a 46-year-old woman who presented with a more than 2-year history of right pyriform fossa mass and progressive hoarseness for three months. The endoscopic examination of the larynx revealed a mass in the right pyriform fossa with smooth surface and well-defined margin. Computed tomography demonstrated a heterogeneous tumor in the right pyriform fossa, and involving the paralaryngeal space, measuring approximately 2.1 cm x 1.7 cm x 2.6 cm, which was resected via lateral neck approach. Histopathology and immunohistochemistry revealed an ASPS. To ours knowledge, this is the first reported case of ASPS arising in pyriform fossa. PMID- 26540931 TI - [Oncocytic carcinoma of the parotid gland: a case report]. AB - Approximately 3% of all head and neck neoplasms originate in the parotid gland and less than 1% are oncocytic. We present the rare case of a 63-year-old woman with oncocytic carcinoma of the parotid gland with facial nerve invasion and discuss the characteristics of this rare entity. Based on the results of medical history, physical examination, computed tomography and postoperative histopathological diagnosis, oncocytic carcinoma of the parotid gland was diagnosed. Treatment involved complete parotid gland removal and right neck dissection. Adjuvant radiotherapy and chemotherapy were followed by operation. As of 9 months following surgery, no recurrence has been identified, but long-term results are undefined. PMID- 26540932 TI - [Cartilaginous tumors of the cricoid: a case report]. AB - Review a case of cricoid cartilaginous tumour in our hospital in December 2013 retrospectively, which received laryngofissure surgery and was followed up for 1 year. The case is still alive without recurrence. The incidence of laryngeal cartilaginous tumour is low, most are cases of cricoid cartilaginous tumour. Try to preserve laryngeal function in surgery as much as possible. PMID- 26540933 TI - [Diagnosis of HIV infection in otolaryngology: a case report]. AB - In the article we described a case of 61-year-old male with pharyngeal paraesthesia for 3 months. Physical examination: lean physique; vast uneven white membrane above hard palate, soft palate and pharynx mucous membrane, not easy to wipe and extend to the throat. The neck without cervical lymph node enlargement. Blood routine test: WBC 4.92 x 10(9)/L, N 64.3%, L 18.7%, EO 7.1%. RBC 4.08 x 10(12)/L, PLT 181 x 10(9)/L. No significant abnormal in the other blood biochemical indexes, tumor marker and immune indexes; blood bacteria culture: negative; blood culture: negative; sputum culture (3 times): all negative; anti HIV screening test: positive, serum HIV testing: positive(the test done by Shanghai Pudong new area's centers for disease control and detection). The incidence of HIV/AIDS is still low at present, so the diagnosis of HIV/AIDS can be ignored easily by the otolaryngology doctor. If the patient with oral cavity and pharyngeal ulcer delayed healing, the doctor should be alert to,HIV/AIDS infection. We should check serum HIV antibody to eliminate or confirm HIV/AIDS earlier. PMID- 26540934 TI - [The research progress in genetic susceptibility of noise-induced hearing loss]. AB - Hazards of noise-induced hearing loss (NIHL) to crowd who are long-term exposured and work in the noisy environment is increasingly prominent. But just part of the individuals who are exposed to the same noisy environment have hearing loss, and the severity of hearing loss are different, which indicates genetic predisposition might be associated with NIHL. In recent years, many experts and scholars at home and abroad have done a lot of research in this field, this article summarizes all available studies. PMID- 26540935 TI - [The role of the cerebellum in auditory process and tinnitus]. AB - Cerebellum connects with each part of the auditory pathway directly or indirectly, forming the anatomical basis for a cerebellar role in auditory process. Functional imaging studies and clinical observations provide more abundant support for this view. Tinnitus is one of the most common clinical manifestations when the auditory system is impaired and remains unsolved. Basic science researches in neurotransmitter chemistry and molecular biochemistry, together with functional imaging studies, indicate that cerebellum might contribute to the pathophysiology of tinnitus. In this review we summarize the current understanding of cerebellar role in auditory process and tinnitus. PMID- 26540936 TI - What Does Consistent Participation in 401(k) Plans Generate? Changes in 401(k) Account Balances, 2007-2013. PMID- 26540937 TI - The Impact of the Affordable Care Act on Large Employers: A Retrospective. AB - The Patient Protection and Affordable Care Act (ACA) has created a new environment for employer health benefit plan management that is influencing costs, benefit design, delivery, administration, financing and compliance as well as the positioning of health care within the benefits portfolio and the broader total rewards strategy. This article will examine the key pragmatic effects of health reform for larger employers to date, quantifying its direct costs and discussing the new dimensions of management that reform has introduced. The discussion will focus on nongrandfathered self-funded plans and will address only major influences. It is not intended to be all-encompassing and is, of necessity, general in nature. Each employer will have somewhat differing experiences and results but should find the discussion to be helpful both in understanding what has evolved as well as what is to come. PMID- 26540938 TI - Total Transformation: How ACA Is Driving Changes in the Provider Landscape. AB - Motivated by Affordable Care Act provisions designed to put the brakes on rapidly increasing health care costs, employers are adopting numerous strategies for creating greater efficiency in how they purchase health care. The strategies are centered on holding providers more accountable for improving patient outcomes and reducing unnecessary expenses. In conjunction with the federal agency for health care, Centers for Medicare and Medicaid Services (CMS), they will drastically transform the provider landscape. This article discusses those strategies, along with their potential impact on providers. PMID- 26540939 TI - Looking Under the Hood--Top Five Open Issues for the Cadillac Tax. AB - The Affordable Care Act's "Cadillac tax" on high-cost group health care plans begins in 2018, yet its expected impact on employers remains an open question. Clarifying regulations, guidance and potential statutory changes between now and then will determine whether employers find the tax to be even more of an administrative burden than a financial one. This article discusses the top five open issues about the application of the tax and its administrative requirements, encouraging employers to use caution in making strategic decisions in advance of clarifying regulations and potential statutory changes. PMID- 26540940 TI - The Benefit Aftereffects of ACA--Accelerating Toward a New Health Economy. AB - While the Affordable Care Act (ACA) focused largely on improving access to health care coverage for the uninsured, its broader and longer-term influence may have been its impact on accelerating key trends and strategies that major employers and other stakeholders have been targeting for years. This article looks at some of these trends, where we were pre-ACA and how ACA (through benefit mandates, shared responsibility penalties, Cadillac plan tax, health information technology, accountable care organizations, etc.) has helped to accelerate and refocus efforts. In addition, the public exchange paradigm has given rise to a private exchange movement that is helping further accelerate the transformation of the New Health Economy. PMID- 26540941 TI - Workforce Health--The Transition From Cost to Outcomes to Business Performance. AB - Although employers can shift the cost/risk of health care to external claims payers through insurance, they can never shift the broader impacts of health related well-being, lost time and performance outside of their organizational boundaries. This article traces the evolution of employer strategies to manage health, addressing what research tells us about the broader impacts of health and well-being on outcomes and establishing a broader framework for connecting health to business performance. The challenge that employers now face is to integrate a much broader set of factors to meet the goals of improved workforce health, well being and business performance. Regardless of how employers decide to provide health benefits, these broader issues are a business imperative for every employer in the 21st century. PMID- 26540942 TI - ACA and the Triple Aim: Musings of a Health Care Actuary. AB - In 2008, the Institute for Healthcare Improvement (IHI) promulgated the Triple Aim, which advocates simultaneous improvements in patient experiences, improved population health and lower cost per capita. In 2010, the Patient Protection and Affordable Care Act (ACA) promised quality, affordable health care for all Americans. It's fair to assume that the framers of ACA were aware of the Triple Aim, and it is likely that much of ACA was heavily influenced by IHI's positions. So it is reasonable, from time to time, to assess ACA's impact on health care against the Triple Aim principles. PMID- 26540943 TI - Dust Off the Historical Approach to Total Compensation. AB - Employers have been afforded new opportunities with the enactment of the Affordable Care Act (ACA). ACA creates a unique opportunity for employers to take a fresh, strategically based total compensation approach to planning. The concept of a total compensation framework is not new; however, a new way to achieve this approach is now possible. Employers need to create their own level playing field, and a total compensation approach is the optimal solution. This article discusses how employers that consider a framework driven toward total compensation accomplish many key objectives. PMID- 26540944 TI - Employer Reactions to the Affordable Care Act. AB - Although the implementation of parts of the Affordable Care Act (ACA) was delayed until 2015, many firms had already made changes to their health insurance plans and their business practices. This article reports results from a survey administered to western Michigan firms in October 2013 requesting information on any changes they made in response to ACA. The authors found that although 89% of employers planned to offer health insurance in 2014, that number dropped to 66% in 2015. The main ways organizations were controlling health costs were by changing prescription coverage, passing on the costs to employees through higher copays and premiums and offering more high-deductible health plans with health savings accounts. Employers also were altering business practices by decreasing future hiring and decreasing the hours of part-time workers. The authors find that many of these changes were due to the uncertainty firms were facing during the ACA implementation process. PMID- 26540945 TI - Long-Term Disability Plan Administration. Melech v. Life Insurance Company of North America, 739 F.3d 663, 57 EBC 1800 (11th Cir. 2014). PMID- 26540946 TI - Benefits Claim Statute of Limitations. Riley v. Metropolitan Life Insurance Company, 744 F.3d 241, 57 EBC 2153 (1st Cir. 2014). PMID- 26540947 TI - Discretion to Deny Benefits. Prezioso v. The Prudential Insurance Company of America, 2014 WL 1356862 (8th Cir. 2014). PMID- 26540948 TI - Statute of Limitations in LTD Termination Appeal. Gordon v. Deloitte & Touche, LLP Group Long-Term Disability Plan, 2014 WL 1394962 (9th Cir. 2014). PMID- 26540949 TI - Review of Disability Claim. Hoffman v. Screen Actors Guild--Producers Pension Plan,_Fed. Appx._, 2014 WL 1664400 (9th Cir. 2014). PMID- 26540950 TI - ICD-10 is upon us! PMID- 26540951 TI - The quest for HIT's holy grail. PMID- 26540952 TI - Countdown to D-Day. PMID- 26540953 TI - Strategies for successful ICD-10 implementation. AB - The transition to ICD-10 is the largest mandate in U.S. healthcare history. Full ICD-10 implementation will require diligent, comprehensive actions. The three pillars to ICD-10 success are the same with any enormous organizational change: governance, education, and documentation. Many organizations have called for additional delays before full implementation, while other organizations across the United States have already made significant strides to prepare for the change. But is another delay of ICD-10 the solution? Many believe not, because any further delays can hinder forward momentum. Organizations that fell behind before the delay haven't taken the extra time to get up to speed, and therefore additional time to prepare isn't likely to motivate them any more than the first delay did. ICD-10 readiness is a journey, but unless the fundamentals are in place, moving toward an Oct. 1 launch is an uphill journey on a very steep slope. But with a solid strategy in place, healthcare organizations can complete the transition, even if they're a little late at the start. PMID- 26540954 TI - Tips for going beyond ICD-10 readiness. PMID- 26540955 TI - Are you financially ready for ICD-10? Five questions to consider. PMID- 26540956 TI - 'Just say no' to paper scripts. PMID- 26540957 TI - Tackling downtime in rural regions. PMID- 26540958 TI - Closing the ICD-10 gap. PMID- 26540959 TI - The Employer-Led Health Care Revolution. AB - To tame its soaring health care costs, intel tried many popular approaches: "consumer-driven health care" offerings such as high-deductible/low-premium plans, on-site clinics and employee wellness programs. But by 2009 intel realized that those programs alone would not enable the company to solve the problem, because they didn't affect its root cause: the steadily rising cost of the care employees and their families were receiving. Intel projected that its health care expenditures would hit a whopping $1 billion by 2012. So the company decided to try a novel approach. As a large purchaser of health services and with expertise in quality improvement and supplier management, intel was uniquely positioned to drive transformation in its local health care market. The company decided that it would manage the quality and cost of its health care suppliers with the same rigor it applied to its equipment suppliers by monitoring quality and cost. It spearheaded a collaborative effort in Portland, Oregon, that included two health systems, a plan administrator, and a major government employer. So far the Portland collaborative has reduced treatment costs for certain medical conditions by 24% to 49%, improved patient satisfaction, and eliminated over 10,000 hours worth of waste in the two health systems' business processes. PMID- 26540960 TI - Accountable Care Organizations: The Missing Link to Engagement in Health and Health Care? AB - Accountable care organizations (ACOs) aim to transform health care delivery and provider payment in a way that improves patient access, engagement and quality of care. If successful, ACOs may help the U.S. health care system finally evolve from a "diagnose, treat and reimburse mostly acute, episodic health care" approach to one that encourages and compensates health care providers that work with their patients throughout a full continuum of care to prevent and manage chronic conditions. What are the implications for ACOs from a workforce health perspective? ACOs were built on a framework for delivering evidence-based health care interventions to engage patients in managing and improving their health. But to what extent do ACOs or employers actually follow such a framework and how can these interventions be integrated with workplace health improvement and wellness efforts? The authors explore the mechanisms for impacting workforce health and provide a checklist to assist employers with evaluating ACOs and assessing feasibility of potential ACO integration with workplace health improvement programs. PMID- 26540961 TI - No Recovery of Profits on Unpaid Benefits. Rochow v. Life Ins. Co. of N. Am., 780 F.3d 364 (6th Cir. 2015). PMID- 26540962 TI - Contraception Coverage. University of Notre Dame v. Burwell,__F.3d_2015 WL 2374764 (7th Cir. May 19, 2015. PMID- 26540963 TI - Limits on Disability Benefits Associated With Mental Disorder. Dutkewych v. Standard Ins. Co., 781 F.3d 623 (1st Cir. Mar. 30, 2015). PMID- 26540965 TI - Official Plan Documents Rule. Prichard v. Metro. Life Ins. Co., 783 F.3d 1166 (9th Cir 2015). PMID- 26540964 TI - Disability Claim Provisions. Clark v. Janssen Pharm., Inc., 2015 WL 1567097,_Fed. Appx._(1st Cir. Apr. 8, 2015) unpublished). PMID- 26540966 TI - Chiropractors' Class Action Certification. Demaria v. Horizon Healthcare Services, No. 11-7298 (D.N.J. June 1, 2015). PMID- 26540967 TI - [BIPADDLED SPLIT PECTORALIS MAJOR MYOCUTANEOUS FLAPS FOR IMMEDIATE RECONSTRUCTION OF ORAL MUCOSAL DEFECTS AND NECK DEFECTS AFTER RESECTION OF RECURRENT ORAL CANCER]. AB - OBJECTIVE: To investigate the feasibility of the bipaddled split pectoralis major myocutaneous flap for immediate reconstruction of oral mucosal defects and neck defects after resection of recurrent oral cancer. METHODS: Six patients with oral mucosal defects combined with neck defects after recurrent oral cancer resection were treated with bipaddled split pectoralis major myocutaneous flap between September 2013 and September 2014. There were 5 males and 1 female with an average age of 54.7 years (range, 45-62 years), including 4 cases of recurrent tongue cancer, 1 case of recurrent mandibular gingival cancer, and 1 case of mouth floor carcinoma. All patients underwent local recurrence at 8 to 14 months after first operation, with no distant metastasis. The defects of the intraoral mucosa was 4.0 cm x 2.5 cm to 6.5 cm x 3.5 cm and the defect of the neck skin was 5.5 cm x 3.5 cm to 7.5 cm x 5.0 cm. The pectoralis major myocutaneous flaps (14.0 cm x 3.5 cm to 17.0 cm x 5.5 cm) were incised at the level of the 3rd to the 4th rib, and then split down along the muscle fiber till about 2 cm away from the thoracoacromial vessels, forming 2 independent skin paddles with 1-2 branch vessels to the pedicles of the distal ones. The distal skin paddles were used for oral reconstruction while the proximal paddles for repair of neck defects. The chest donor sites were sutured directly. RESULTS: Cervical haematoma and infection happened in 1 patient respectively after operation, and were cured after symptomatic treatment. All 6 split pectoralis major myocutaneous flaps with 12 skin paddles completely survived. All patients were followed up 6 to 18 months (mean, 11 months). One patient died of pulmonary metastasis at 8 months after operation and the other 5 survived without relapse or metastasis during follow up. The intraoral paddles showed good shape with satisfactory speech function and swallowing recovery. The paddles also healed perfectly on the neck with flat outlooks, and all patients obtained full appearance and free movement of the neck. No fistula formed on the submandibular region and neck. CONCLUSION: The bipaddled split pectoralis major myocutaneous flap can complete simultaneous immediate reconstruction of oral mucosal defect and neck defect. It is very useful in the treatment of recurrent oral cancer. PMID- 26540968 TI - [DORSALIS PEDIS FLAP SERIES-PARALLEL BIG TOE NAIL COMPOSITE TISSUE FLAP TO REPAIR HAND SKIN OF DEGLOVING INJURY WITH THUMB DEFECT]. AB - OBJECTIVE: To investigate the effectiveness of dorsalis pedis flap series parallel big toe nail composite tissue flap in the repairment of hand skin of degloving injury with tumb defect. METHODS: Between March 2009 and June 2013, 8 cases of hand degloving injury with thumb defect caused by machine twisting were treated. There were 7 males and 1 female with the mean age of 36 years (range, 26 48 years). Injury located at the left hand in 3 cases and at the right hand in 5 cases. The time from injury to hospitalization was 1.5-4.0 hours (mean, 2.5 hours). The defect area was 8 cm x 6 cm to 15 cm x 1 cm. The thumb defect was rated as degree I in 5 cases and as degree II in 3 cases. The contralateral dorsal skin flap (9 cm x 7 cm to 10 cm x 8 cm) combined with ipsilateral big toe nail composite tissue flap (2.5 cm x 1.8 cm to 3.0 cm x 2.0 cm) was used, including 3 parallel anastomosis flaps and 5 series anastomosis flaps. The donor site of the dorsal flap was repaired with thick skin grafts, the stumps wound was covered with tongue flap at the shank side of big toe. RESULTS: Vascular crisis occurred in 1 big toe nail composite tissue flap, margin necrosis occurred in 2 dorsalis pedis flap; the other flaps survived, and primary healing of wound was obtained. The grafted skin at dorsal donor site all survived, skin of hallux toe stump had no necrosis. Eight cases were followed up 4-20 months (mean, 15.5 months). All flaps had soft texture and satisfactory appearance; the cutaneous sensory recovery time was 4-7 months (mean, 5 months). At 4 months after operation, the two-point discrimination of the thumb pulp was 8-10 mm (mean, 9 mm), and the two-point discrimination of dorsal skin flap was 7-9 mm (mean, 8.5 mm). According to Society of Hand Surgery standard for the evaluation of upper part of the function, the results were excellent in 4 cases, good in 3 cases, and fair in 1 case. The donor foot had normal function. CONCLUSION: Dorsalis pedis flap series-parallel big toe nail composite tissue flap is an ideal way to repair hand skin defect, and reconstructs the thumb, which has many advantages, including simple surgical procedure, no limitation to recipient site, soft texture, satisfactory appearance and function of reconstructing thumb, and small donor foot loss. PMID- 26540969 TI - [ANTEROLATERAL THIGH FLAP PEDICLED WITH MEDIAL SURAL VESSELS AS RECIPIENT VESSELS IN RECONSTRUCTION OF LEG SKIN AND SOFT TISSUE DEFECTS]. AB - OBJECTIVE: To discuss the effectiveness of free anterolateral thigh flap pedicled with medial sural vessels for treatment of leg skin and soft tissue defects. METHODS: Between July 2008 and January 2014, 32 cases of serious skin and soft tissue defects in the leg were repaired by using free anterolateral thigh flap pedicled with medial sural artery and vein. Of them, there were 22 males and 10 females, aged 23 to 50 years (mean, 36.5 years). Defects were caused by traffic accidents injury in 9 cases, crash injury of heavy object in 15 cases, and machine twist injury in 8 cases. The left side was involved in 10 cases and the right side in 22 cases. The mean interval of injury and admission was 2.5 hours (range, 1-4 hours). The location was the upper, middle, and lower one third of the anterior tibia in 15 cases, 10 cases, and 7 cases respectively. The area of defect ranged from 10 cm x 5 cm to 23 cm x 9 cm. After debridement and vaccum sealing drainage treatment, the anterolateral thigh flap ranging from 12 cm x 7 cm to 25 cm x 11 cm pedicled with the medial sural vessels was used to repair the wound. The donor site was sutured directly or repaired with the skingrafts. RESULTS: All flaps and skingrafts survived after operation, and primary healing of wound was obtained. After 6-23 months (mean, 14.5 months) follow-up, all flaps were characterized by soft texture, good color, and satisfactory appearance. The sensation of the flaps were recovered to S(2-)S(3+) according to the Britain's Medical Research Council criteria at 6 months after operation. No obvious scar contracture was observed at donor site. CONCLUSION: The medial sural artery has the advantages of constant anatomical position, large diameter, rich blood flow, and a long artery pedicle, so the medial sural vessels is an ideal choice as recipient vessels for the reconstruction of leg skin and soft tissue defect. PMID- 26540970 TI - [APPLICATION OF DIGITAL TECHNOLOGY IN ANTEROLATERAL THIGH FLAP FOR REPAIRING WOUNDS OF HAND AND FOOT]. AB - OBJECTIVE: To investigate the effectiveness of digital technology in repairing wounds of the hand and foot with anterolateral thigh flap. METHODS: Between September 2013 and September 2014, 16 cases of wounds of the hand and foot were treated with the anterolateral thigh flap. There were 10 males and 6 females, with an average age of 31 years (range, 20-52 years). The causes included traffic accident injury in 8 cases, crushing injury by machine in 6 cases, burning injury in 1 case, and animal biting injury in 1 case. The locations of soft tissue defect were the dorsum of the foot in 5 cases, the ankle in 4 cases, the planta pedis in 1 case, and the hand and forearm in 6 cases. The time was 2 hours to 45 days from injury to hospitalization (mean, 14.3 days). All defects were associated with exposure of bone and tendon. The size of wound was from 9.0 cmx4.0 cm to 29.0 cmx8.5 cm. CT angiography (CTA) was performed before operation, and the appropriate perforator as well as the donor site was selected. Then the Mimics l5.0 software was used to reconstruct the data of CTA so as to locate the main perforators, design the three-dimensional models of the anterolateral thigh flap, and simulate operation. The flap was obtained according to preoperative plan during operation. The size of flaps varied from 11 cm x 5 cm to 31 cm x 10 cm. The donor sites were sutured directly in 14 cases and were repaired by free skin graft in 2 cases. RESULTS: The lateral femoral circumflex artery identified by Mimics l5.0 software before operation, as well as the starting position of its descending branch, the blood vessel diameter at start site, vascular distribution, the maximum cutting length of the vascular pedicle were consistent with the actual observation during operation. All flaps were harvested and were used to repair defect smoothly. Vascular crisis occurred in 1 flap after operation, and the other flaps survived successfully. The wounds and the incisions obtained healing by first intention, and grafted skin survived completely. All cases were followed up 6-17 months (mean, 9 months). Fifteen flaps had good shape; but a second- stage operation was performed to make the flap thinner in 1 case. At last follow-up, the results were excellent in 3 cases, good in 2 cases, and fair in 1 case according to total active motion (TAM) in 6 cases of hand and forearm injury; the results were excellent in 5 cases, good in 3 cases, and fair in 2 cases according to American Orthopaedic Foot and Ankle Society (AOFAS) in 10 cases of foot injury. The total excellent and good rate was 81.25%. CONCLUSION: The preoperative individualization design of the flap can be realized through CTA digital technology and Mimics 15.0 software; it can reduce the operation risk. PMID- 26540971 TI - [EFFECTS OF INTERMITTENT IRRIGATION OF INSULIN SOLUTION COMBINED WITH CONTINUOUS DRAINAGE OF VACUUM SEALING DRAINAGE IN CHRONIC DIABETIC LOWER LIMB ULCERS]. AB - OBJECTIVE: To investigate the effects of intermittent irrigation of insulin solution combined with continuous drainage of vacuum sealing drainage (VSD) in chronic diabetic lower limb ulcers. METHODS: Between January 2012 and December 2014, 45 patients with diabetic lower limb ulcer were treated with VSD (group A, n=15), with VSD combining irrigation of normal saline (group B, n=15), and with VSD combining irrigation of insulin solution (group C, n=15) after debridement. There was no significant difference in gender, age, course of ulcers, area and depth of wound, glycosylated hemoglobin, and Wagner grade among 3 groups (P>0.05), and the data were comparable. The levels of fasting blood glucose, 2 hour postprandial blood glucose, and random blood glucose were determined everyday during treatment. The contents of insulin growth factor 1 (IGF-1), tumor growth factor a (TNF-alpha), and nitric oxide (NO) in necrotic tissue after drainage were determined. The coverage rate and thickness of granulation tissue and clearance rate of bacteria in wound were calculated, the granulation tissue in the center of the wound was harvested for pathological observation with HE staining after 6 days of treatment. The second stage operation was performed according to the condition of wounds, and the time to the second stage operation and the method of the second stage operation were recorded and the survival rate of grafted skin or flap was calculated. RESULTS: The pathological staining showed that there were a few new microvessels and fibroblasts in group A after treatment; more new microvessels and fibroblasts were observed in group B; and many new microvessels and fibroblasts were found in group C. There was no significant difference in levels of fasting blood glucose, 2-hour postprandial blood glucose, and random blood glucose among 3 groups during treatment (P > 0.05). The coverage rate and thickness of granulation tissue and clearance rate of bacteria in group C were significantly higher than those in groups A and B after treatment (P < 0.05). The contents of IGF-1 and NO were significantly increased and TNF-alpha was significantly decreased in group C when compared with those in group A (P < 0.05). Compared with group B, IGF-1 and NO contents were significantly increased at 3-6 days and at 2-6 days respectively, and TNF-alpha content was significantly decreased at 3-6 days in group C (P < 0.05). The method of the second stage operation showed no significant difference among 3 groups (chi2 = 2.920, P = 0.230), but the time to the second stage operation in group C was significantly shorter than that in groups A and B (P < 0.05), and the survival rate of grafted skin or flap in group C was significantly higher than that in groups A and B (P < 0.05). CONCLUSION: The treatment of diabetic lower limb ulcers with intermittent irrigation of insulin solution combined with continuous drainage of VSD can reduce inflammatory reaction effectively, promote development of granulation tissue, improve recovery function of tissue, increase the rate and speed of wound healing obviously, but it has no effect on blood glucose levels. PMID- 26540972 TI - [EFFECTIVENESS ANALYSIS OF OLD EXTENSOR TENDON INJURY IN ZONE II]. AB - OBJECTIVE: To discuss the effectiveness of operative treatments for different kinds of old injury of extensor tendon in zone II so as to choose the best surgical approach based on the classification of injury. METHODS: Between May 2006 and May 2014, 68 cases of old injury of extensor tendon in zone II were treated. Among them, there were 50 males and 18 females with an average age of 36 years (range, 18-52 years). The causes included contusion injury in 50 cases, avulsion injury in 11 cases, and burn injury in 7 cases. The left side was involved in 21 cases and the right side in 47 cases. The injured finger involved the index finger in 18 cases, the middle finger in 21 cases, the ring finger in 24 cases, and the little finger in 5 cases. The disease duration was 1.5 months to 1 year (mean, 6.75 months). The central slip of extensor was repaired directly in 32 patients who had normal passive motion. Side cross stitch (8 cases) or Littler-Eaton (10 cases) method was used in 18 patients who can not extend actively and passively. Tendon graft was performed in 11 patients with tendon defect. Joint release was given in 7 patients with contracture after burn injury. RESULTS: Primary healing of incision was obtained in all cases. Sixty-eight cases were followed up 3-12 months (mean, 6.9 months). Three cases had tendon adhesion in varying degrees and suffered from pain, which was treated conservatively by functional exercise. Recurrence was observed in 2 cases, and extensor tendon was repaired again. According to total active motion (TAM) function assessment, the results were excellent in 52 cases, good in 11 cases, fair in 3 cases, and poor in 2 cases with an excellent and good rate of 92.6%. CONCLUSION: Adaptive operation method for old injury of extensor tendon in zone II should be selected based on the type of injury. The results will be satisfactory if correct method is chosen. PMID- 26540973 TI - [CLINICAL RESEARCH AND DISCUSSION OF MODIFIED CRANIOPLASTY]. AB - OBJECTIVE: To study and design a modified cranioplasty, and to explore the effectiveness so as to reduce the incidence rate of operative complications. METHODS: A total of 68 patients with craniocerebral trauma or hypertensive cerebral hemorrhage between August 2012 and March 2014 were selected and randomly divided into 2 groups. The standard decompress craniectomy and under-temporal cranioplasty were performed in 32 cases (group A), and several small bone chips were placed under-tempus during decompress craniectomy and then the shape of temporal muscle was designed and the temporal muscle was reconstructed at the attachment sites during cranioplasty in 36 cases (group B). No significant difference was found in gender, age, side of operation, cause of injury, time between injury and decompress craniectomy, and time between postoperation and cranioplasty between 2 groups (P > 0.05). Then the postoperative complications were compared between the 2 groups. RESULTS: Primary healing of incision was obtained in all patients. The patients were followed up 12 months on average (range, 6-16 months) in 2 groups. The follow complications occurred in group A: 4 cases of asymmetric appearance (12.50%), 12 cases of temporal muscle atrophy (37.50%), 6 cases of temporal pain and masticatory atonia (18.75%), 2 cases of epilepsy (6.25%), 9 cases of leakage of cerebrospinal fluid (28.13%), 1 case of cerebral contusion and laceration (3.13%), and 1 case of cerebral hemorrhage (3.13%); temporal muscle atrophy was observed in 2 cases (5.56%) and the rate of complication was significantly lower than that in group A (P < 0.05). The symmetrical appearance of the skull and good function were achieved in the other patients having no complication. CONCLUSION: New technique of setting bone chip markers during decompress craniectomy and reconstructing temporal muscle during cranioplasty can reduce the incidence of complications and thus it is an effective surgical procedure. PMID- 26540974 TI - [OPEN ARTHROLYSIS COMBINED WITH INTERNAL FIXATOR REMOVAL FOR POST-TRAUMATIC ELBOW STIFFNESS]. AB - OBJECTIVE: To explore the effectiveness and safety of open arthrolysis combined with internal fixator removal for post-traumatic elbow stiffness. METHODS: A retrospective analysis was made on the data of 80 cases treated by open arthrolysis for elbow stiffness between January 2010 and December 2011. The patients were divided into 2 groups: no internal fixation group (group A, n = 39) and internal fixation group (group B, n = 41) according to whether they underwent internal fixator removal at the same time. No significant difference was found in age, gender, affected side, injury time, elbow rigidity grade, and severity of heterotopic ossification (HO) between 2 groups (P > 0.05) except for original injury type (P < 0.05). The effectiveness was evaluated by the occurrence of complications including ulnar nerve symptoms, HO recurrence and re-fracture, the elbow range of motion (ROM) and the Mayo elbow performance score (MEPS). RESULTS: The mean follow-up duration was 15.7 months (range, 12-18 months) in group A and 16.1 months (range, 12-20 months) in group B. Ulnar nerve symptoms in 5 cases (12.8%) and HO reccurrence in 1 case (2.6%) occurred in group A, while ulnar nerve symptoms in 4 cases (9.8%), HO recurrence 1 case (2.4%), and refracture in 1 case (2.4%) occurred in group B. The incidence of each complication showed no significant difference between 2 groups (P > 0.05). Both the ROM and the MEPS at last follow-up increased significantly when compared with preoperative ones in 2 groups (P < 0.05). Besides, MEPS of group A was significantly higher than that of group B (t = 2.36, P = 0.02), but no significant difference was found in the ROM between 2 groups at last follow-up (t = 0.40, P = 0.69). Based on MEPS, the results were excellent in 16 cases, good in 16 cases, fair in 6 cases, and poor in 1 case in group A with an excellent and good rate of 82.1%; the results were excellent in 10 cases, good in 25 cases, fair in 4 cases, and poor in 2 cases in group B with an excellent and good rate of 85.4%. There was no significant difference in excellent and good rate between 2 groups (chi2 = 0.16, P = 0.69). CONCLUSION: Open elbow arthrolysis combined with internal fixator removal for post-traumatic elbow stiffness is safe and effective. However, measures for prevention of re-fracture should always be taken into consideration. PMID- 26540975 TI - [EFFECTIVENESS OF Bernese OSTEOTOMY FOR TREATMENT OF DEVELOPMENTAL DYSPLASIA OF THE HIP IN ADULTS]. AB - OBJECTIVE: To investigate the effectiveness of Bernese osteotomy for the treatment of developmental dysplasia of the hip (DDH) in adults. METHODS: Between August 2012 and April 2014, 16 patients with DDH were treated with Bernese osteotomy by S-P approach, and the clinical data were retrospectively analyzed. There were 4 males and 12 females with an average age of 27.8 years (range, 18-35 years). The left side was involved in 6 cases and the right side in 10 cases. The visual analogue scale (VAS) score was 4.8 +/- 0.5, and the Harris hip score was 81.2 +/- 5.4. The lateral center edge (CE) angle (the angle between the vertical center of the femoral head and the lateral edge of the acetabulum) was (6.5 +/- 8.7); the horizontal tilt angle was (25.6 +/- 5.9); and the femoral head extrusion index was 36.5% +/- 6.5%. According to the Tonnis osteoarthritis classification, 12 hips were rated as Grade 0, 3 hips as Grade I, and 1 hip as Grade II. RESULTS: The operation time was 90-135 minutes; the intraoperative blood loss was 400-800 mL; 10 cases accepted blood transfusion and the amount of blood transfusion was 200-600 mL; the postoperative drainage volume was 100- 300 mL; and the hospitalization time was 7-12 days. All the cases achieved primary healing of incision with no early complications. Two cases had numb in the lateral femoral cutaneous nerve innervating area. All patients were followed up 12-26 months (mean, 20 months). The X-ray examination showed osseous healing at osteotomy site, and the healing time was 12-16 weeks (mean, 13.5 weeks). No acetabulum fracture, heterotopic ossification, osteonecrosis, and internal fixation loosening occurred during follow-up. No progression of osteoarthritis or acetabular cystic change was observed. At last follow-up, the lateral CE angle was (27.7 +/- 6.8); the horizontal tilt angle was (16.2 +/- 4.8) degrees ; the femoral head extrusion index was 19.7% +/- 5.3%; VAS score was 0.8 +/- 0.3; the Harris hip score was 96.8 +/- 6.7; and all showed significant differences when compared with preoperative ones (P < 0.05). CONCLUSION: For DDH adults, Bernese osteotomy can effectively increase the acetabulum tolerance, improve the joint function, and slow progress in osteoarthritis, and the short-term effectiveness is satisfactory. PMID- 26540976 TI - [VASCULAR ANATOMICAL STUDY ON TIBIAL OSTEOTOMY LENGTHENING]. AB - OBJECTIVE: To provide the anatomical basis for the selection of osteotomy site in leg lengthening or tibial slip. METHODS: Between August 2010 and July 2014, 10 adult fresh amputated leg specimens were collected. The pressure perfusion of red latex was performed by the popliteal artery. The anterior tibial artery and its main branches were separated and exposed, and the periosteal branch of anterior tibial artery was adequately exposed; the posterior tibial artery and its main branches were exposed; the peroneal artery was separated and exposed. The tibial and peroneal artery and its branches were observed and measured. When measuring the proximal end, the medial tibial plateau bone margin, the most prominent part of the tibial tuberosity, and the fibular head edge were used as a reference; when measuring the distal end, distal medial condyle of tibia malleolus tip, tibial lateral malleolus lateral tip, and distal tibial articular surface were used as a reference; the vertical distance between tibia proximal and distal main arteries and bone end reference was measured to determine the optimal osteotomy position of upper and lower tibia. The osteotomy index was calculated which was used to represent the relative position of osteotomy site in the whole tibia. RESULTS: The proximal tibial osteotomy site located at (78.2 +/- 19.5) mm from medial tibial plateau margin, (41.8 +/- 16.0) mm from the tibial tuberosity pole, and (66.7 +/- 16.4) mm from the fibular head edge. The distal tibial osteotomy site located at (70.8 +/- 12.1) mm above the inferior margin of tibial medial malleolus, (83.3 +/- 13.0) mm above the inferior margin of lateral malleolus tip, and (59.1 +/- 11.7) mm from distal tibial articular surface. The proximal tibial osteotomy index was 18.45-23.35 (mean, 20.46); the distal tibial osteotomy index was 14.36-23.05 (mean, 18.81). CONCLUSION: The metaphyseal-diaphyseal connection shold be selected in the proximal and distal tibia osteotomy, the lower one third of the tibia is not suitable for ostetomy. PMID- 26540977 TI - [EFFECTIVENESS COMPARISON BETWEEN ANTERIOR CERVICAL ZERO- PROFILE INTERBODY FUSION DEVICE AND ANTERIOR CERVICAL PLATE CAGE BENEZECH]. AB - OBJECTIVE: To compare the effectiveness between anterior cervical Zero-profile interbody fusion device (Zero-P) and anterior cervical plate device (plate cage benezech, PCB) for cervical disease. METHODS: Between February 2011 and January 2013, 98 patients with cervical spondylosis who accorded with the inclusion criteria were treated with Zero-P in 49 cases (group A) and with PCB in 49 cases (group B). There was no significant difference in gender, age, disease type, disease duration, and disease segments between 2 groups (P>0.05). The Cobb angle, short-form 36 health survey scale (SF-36 scale), Japanese Orthopedic Association (JOA) score, postoperative dysphagia cases, neck disability index (NDI), and visual analogue scale (VAS) score were compared between 2 groups. RESULTS: The operation time and intraoperative blood loss of group A were significantly less than those of group B (t = 4.089, P = 0.000; t = 3.587, P = 0.001). The patients were followed up 3-36 months (mean, 18.5 months). No loosening or breaking of internal fixation and bone absorption or collapse occurred in the other patients except 2 patients who suffered from screw loosening at 3 months after operation. Within 6 months after operation, dysphagia occurred in 8 cases (16.33%) of group A and in 13 cases (26.53%) of group B, showing significant difference (chi2 = 10.616, P = 0.001). At last follow-up, JOA score, VAS score, NDI, SF-36 scale, and Cobb angle were significantly improved when compared with preoperative ones in 2 groups (P<0.05); the other indexes of group A were significantly better than those of group B (P < 0.05) except SF-36 scale and Cobb angle (P>0.05). The excellent and good rate of JOA score was 81.63% in group A and 71.43% in group B, showing significant difference (chi2 = 4.346, P = 0.037). CONCLUSION: Zero-P and PCB can get good results in treatment of cervical disease, but the Zero-P is better than PCB in reducing postoperative dysphagia because less wounds and strong stability. PMID- 26540978 TI - [APPLICATION OF HIGH VISCOSITY BONE CEMENT IN UNILATERAL PUNCTURE PERCUTANEOUS VERTEBROPLASTY FOR TREATMENT OF FRESH VERTEBRAL FRACTURE]. AB - OBJECTIVE: To discuss the effectiveness of high viscosity bone cement in unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic fresh vertebral fracture and operation skills of the bone cement leakage prevention. METHODS: Between November 2005 and October 2013, 82 elderly patients with fresh thoracolumbar vertebral fracture were first treated with hyperextension postural reduction and then with high viscosity bone cement in unilateral pedicle puncture PVP. Of 82 cases, 25 were male and 57 were female with an average age of 72.3 years (range, 61-90 years). The causes included falling injury in 28 cases, sprain injury in 11 cases, car shock injury in 4 cases, fracture by cough or sneeze in 6 cases, and no obvious reason in 33 cases. The time from injury to operation was 3-15 days (mean, 7.6 days). Single segment was involved in 74 cases, and double segments in 8 cases. The operation time, fluoroscopy time, intraoperative blood loss, and hospitalization time were recorded, bone cement leakage was observed; pain visual analogue scale (VAS) was used to evaluate pain relief effect; X-ray films were taken for measurement of the Cobb angle and anterior vertebral body height compression ratio to evaluate the correction effect. RESULTS: The average operation time was 16 minutes; the average fluoroscopy time was 48 seconds; the average hospitalization time was 3 days. All cases were followed up from 6 to 18 months (mean, 6.8 months). Leakage of bone cement occurred in 6 cases (7.3%), including 3 cases of paravertebral soft tissue leakage, 1 case of intervertebral disc leakage, and 2 cases of venous leakage. There was no nerve damage or paralysis. At last follow-up, VAS score was significantly decreased to 1.3 +/- 0.9 from preoperative 8.8 +/- 1.2 (t = 73.891, P = 0.000); Cobb angle was significantly reduced to (25.06 +/- 6.18) degrees from preoperative (34.79 +/- 7.18) degrees (t = 18.878, P = 0.000); and the anterior vertebral body height compression ratio was significantly increased to 67.8% +/- 5.7% from preoperative 41.3% +/- 9.8% (t = 36.880, P =0.000). CONCLUSION: Application of high viscosity bone cement in unilateral puncture PVP can shorten operation time, reduce bone cement leakage rate, and achieve satisfactory effectiveness. PMID- 26540979 TI - [LONG-TERM EFFECTS ON LOWER LIMB FUNCTION AFTER S1 NERVE ROOT TRANSECTION AS DYNAMIC SOURCE]. AB - OBJECTIVE: To evaluate the long-term effects on the lower limb function after S nerve root transection as dynamic source. METHODS: Between January 2007 and December 2011, 47 patients with atonic bladder dysfunction underwent S1 nerve root transposition to reconstrut the bladder function. There were 43 males and 4 females, with an average age of 40.7 years (range, 22-66 years). The locations were L1 in 33 cases, L2 in 5 cases, L3 in 2 cases, T12, L, in 3 cases, L1, L2 in 1 case, L1, L3in 1 case, L1, L4 in 1 case, and L2, L3 in 1 case. The anastomosis of the S2 or S3 nerve root to S1 nerve root was performed from 4 to 24 months (mean, 8 months) after spinal cord injury. The strength of ande plantar flexion was grade 4 in 5 cases and grade 5 in 42 cases before operation. RESULTS: The strength of ande plantar flexion had no obvious decrease (grade 4 or 5) in 31 cases, reduced 0.5 grade in 16 cases at 2 days after operation. All the patients were followed up 3-8 years (mean, 5.1 years). At 2 weeks after operation, the nerve electrophysiological examination showed neurogenic damage at operated side in most patients, including reduced amplitude tibial nerve in 19 cases, for common peroneal nerve in 13 cases, and for tibial nerve and common peroneal nerve in 9 cases. Except the velocity of common peroneal nerve (t = -1.881, P = 0.093), the other electric physiological indexes showed significant differences between at pre- and post-operation (P < 0.05). The muscle strength basically recovered to preoperative level (grade 4 or 5) during follow-up, and there was no impairment of lower limb function. CONCLUSION: S1 transection has no significant effects on lower limb function, so S1 nerve can be used as dynamic nerve for nerve function reconstruction. PMID- 26540980 TI - [STUDY ON RELATIONSHIP BETWEEN DIFFUSION TENSOR IMAGING AND VISUAL EVOKED POTENTIAL IN VISUAL PATHWAY OF NEUROMYELITIS OPTICA]. AB - OBJECTIVE: To study the relationship between brain white matter fiber occult lesions and P100 wave latency of visual evoked potential (VEP) in neuromyelitis optica (NMO) patients by diffusion tensor imaging (DTI). METHODS: Twenty patients with NMO who were treated between July 2008 and April 2009 were selected as the trial group. According to the VEP test, the latency of P100 wave was prolonged, the NMO patients were divided into VEP abnormal group (trial group 1) and VEP normal group (trial group 2). Twenty healthy adult volunteers served as the control group. The DTI examination in brain was done to measure the fractional anisotropy (FA) value of optic nerve (FAn), optic tract (FAt), and optic radiation (FAr); and the mean diffusivity (MD) value of optic nerve (MDn), optic tract (MDt), and optic radiation (MDr). The FA, MD, and P100 wave latency were compared between groups, and the correlation between MD, FA, and P100 wave latency of NMO were analyzed. RESULTS: In the 20 NMO patients, 13 patients with VEP had prolonged bilateral P100 wave latency prolongation or no wave (trial group 1), and 7 patients had normal bilateral P100 wave latency (trial group 2). Compared with the trial group 2 and the control group, the FA values were significantly decreased, and the MD values were significantly increased in the trial group 1 (P < 0.05). There was no significant difference in the FA and MD values between the trial group 2 and the control group (P > 0.05). All FA (FAn, FAt, and FAr) values of each part of NMO patients were negatively correlated with the latency of P100 wave (P < 0.05), all MD (MDn, MDt, and MDr) values were positively correlated with the latency of P100 wave (P < 0.05). CONCLUSION: DTI could show small pathylogical changes in the white matter fibers of visual pathway, and there is a correlation between DTI and VEP in NMO, suggesting that a more comprehensive assessment to the condition and prognosis can be made through the VEP in the clinical indicators. PMID- 26540981 TI - [HYPOXIA INDUCIBLE FACTOR lalpha/2alpha GENES EXPRESSION IN CHONDROGENIC DIFFERENTIATION OF HUMAN BONE MARROW MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To observe the genes expression of hypoxia inducible factor lalpha (HIF-1alpha) and HIF- 2alpha by inducing chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) so as to provide a fundamental basis for HIF involving in the mechanism of chondrogenesis. METHODS: High density pellet of hBMSCs was obtained by centrifugation and cultured with H-DMEM medium containing 2% fetal bovine serum (control group) and with chondrogenic medium (chondrogenic induction group) under hypoxia (2% O2) for 3 weeks. Immunohistochemistry staining was utilized to identify extracellular proteoglycan and collagen type II at 3 weeks after culture. Western blot was applied for measuring HIF-1alpha and HIF-2alpha protein levels at 1 week after culture. Real time quantitative PCR was performed to detect the genes expressions of HIF 1alpha, HIF-2alpha, Sox-9, collagen type II, collagen type X, and Aggrecan at 1, 2, and 3 weeks after culture. RESULTS: Toluidine blue staining showed sparse nucleus in the control group, and dense nucleus in the chondrogenic induction group; extracellular matrix staining was deeper in the chondrogenic induction group than the control group. Immunohistochemical staining for collagen type II was positive in cytoplasm; when compared with the chondrogenic induction group, the control group showed sparse and light-coloured nucleus. At 1 week after culture, the protein expression levels of HIF-1alpha and HIF-2alpha in the chondrogenic induction group were significantly lower than those in the control group (t = 8.345, P = 0.001; t = 7.683, P = 0.002). When compared with control group, the HIF-1alpha mRNA expression was significantly down-regulated at 1 week and significantly up-regulated at 2 weeks in chondrogenic induction group (P < 0.05), but no significant difference was found at 3 weeks between the 2 groups (P > 0.05). And the mRNA expression of HIF-2alpha was significantly down-regulated and mRNA expression of Sox-9 was significantly up-regulated after chondrogenic differentiation when compared with the control group (P < 0.01). The mRNA expressions of collagen type II and collagen type X were significantly up regulated at 2 and 3 weeks after chondrogenic differentiation when compared with the control group (P < 0.05). And the mRNA expression of Aggrecan was significantly up-regulated at each time point after chondrogenic differentiation (P < 0.05). CONCLUSION: HIF-1alpha may involve the hBMSCs chondrogenic differentiation under hypoxia, while HIF-2alpha expression is depressed throughout the period and may have negative effect on differentiation. PMID- 26540982 TI - [ISOLATION AND IDENTIFICATION OF CARTILAGE PROGENITOR CELLS AND INFLUENCE OF INTERLEUKIN 1beta ON ITS CHONDROGENESIS]. AB - OBJECTIVE: To isolate and identify the cartilage progenitor cells (CPCs) from normal cartilage, and to explore the influence of interleukin 1beta (IL-1beta) in different concentrations on its chondrogenesis. METHODS: CPCs were isolated from normal cartilage of adult New Zealand white rabbit with the fibronectin adhesion assay; the cell phenotype was identified; and the cloning and differentiation of CPCs were observed. CPCs were incubated with H-DMEM in group A, with chondrogenic induced medium in group B, with chondrogenic induced medium+0.1 ng/mL IL-1beta in group C and chondrogenic induced medium+1.0 ng/mL IL-1beta in group D for 3 weeks. The histology, biochemistry, and real-time fluorescence quantitative PCR were performed to observe the effect of IL-1beta on the chondrgenic differentiation. RESULTS: The CPCs from normal cartilage expressed positively stem cell phenotype, which have similar ability of cloning and differentiation to stem cells. The cell pellets in groups C and D were significantly smaller than those in group B, and cell showed hypertrophic morphology change. There were more expressions of collagen type II and collagen type X in group B than in group A, in group B than in groups C and D, and in group C than group D with Safranin O staining. The biochemistry results showed that collagen type II content, glycosaminoglycan (GAG) content, and the ratio of GAG/DNA were significantly lower in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05); but the DNA content was significantly higher in groups C and D than in group B (P < 0.05), and no significant difference between groups C and D (P > 0.05). The real-time fluorescence quantitative PCR results showed that the relative mRNA expressions of collagen type II, collagen type X, and Sox-9 were significantly lower in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05), but the relative mRNA expressions of Runx-2 and matrix metalloproteinase 13 were significantly higher in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05). CONCLUSION: There are CPCs having the character of stem cells in normal cartilage, and they have the capability of cloning and potential differentiation. IL-1beta can inhibit the chondrogenesis of CPCs, and possibly promote the osteogenic differentiation. PMID- 26540983 TI - [BIOLOGICAL FEATURES AND IDENTIFICATION OF ENDOTHELIAL PROGENITOR CELLS FROM PERIPHERAL BLOOD]. AB - OBJECTIVE: To compare the biological features of early and late endothelial progenitor cells (EPCs) by isolating and culturing early and late EPCs from the human peripheral blood so as to find some unique properties of EPCs and to propose a suitable strategy for EPCs identification. METHODS: Mononuclear cells were isolated from the human peripheral blood using density gradient centrifugation. Then, the cells were inoculated in human fibronectin-coated culture flasks and cultured in endothelial cell basal medium 2. After 4-7 days and 2-3 weeks culture, early and late EPCs were obtained respectively. The morphology, proliferation potential, surface markers, cytokine secretion, angiogenic ability, and nitric oxide (NO) release were compared between 2 types of EPCs. Meanwhile, the human aortic endothelial cells (HAECs) were used as positive control. RESULTS: The morphology of early and late EPCs was different: early EPCs formed a cell cluster with a spindle shape after 4-7 days of culture, and late EPCs showed a cobblestone appearance. Late EPCs were characterized by high proliferation potential and were able to form capillary tubes on Matrigel, but early EPCs did not have this feature. Both types EPCs could ingest acetylated low density lipoprotein and combine with ulex europaeus I. Flow cytometry analysis showed that early EPCs did not express CD34 and CD133, but expressed the CD14 and CD45 of the hematopoietic stem cell markers; however, late EPCs expressed CD31 and CD34 of the endothelial cell markers, but did not express CD14, CD45, and CD133. By RT-PCR analysis, the expressions of vascular endothelial growth receptor 2 and vascular endothelial cadherin in early EPCs were significantly lower than those in the late EPCs and HAECs (P < 0.05), but no significant difference was found in the expression of von Willebrand factor and endothelial nitric oxide synthase (eNOS) between 2 type EPCs (P > 0.05). The concentrations of vascular endothelial growth factor, granulocyte colony stimulating factor, and interleukin 8 were significantly higher in the supernatant of early EPCs than late EPCs (P < 0.05). Western blot assay indicated eNOS expressed in both types EPCs, while the expression of eNOS in late EPCs was significantly higher than early EPCs at 5 weeks (P < 0.05). Both cell types could produce similar amount of NO (P > 0.05). CONCLUSION: The expression of eNOS and the production of NO could be used as common biological features to identify EPCs, and the strategy of a combination of multiple methods for EPCs identification is more feasible. PMID- 26540984 TI - [DIFFERENTIATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS INTO HEPATOCYTES INDUCED BY RAT FIBROTIC LIVER TISSUE EXTRACTS]. AB - OBJECTIVE: To investigate the differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes induced by rat fibrotic liver tissue extracts. METHODS: Liver fibrosis was induced in the Sprague Dawley rats (weighting, 180-220 g) by repeated intraperitoneal injections of 3% thioacetamide saline at a dose of 200 mg/kg twice a week for 4 weeks; fibrotic liver tissues were used to prepare liver homogenate supernatants. The HUCMSCs at passage 3 were cultured in DMEM/F12 with 10% fetal bovine serum (FBS) (control group) and in DMEM/F12 with 10% FBS and 50 g/L liver homogenate supernatants (experimental group) for 7 days. The morphological changes of the cells were recorded; the protein levels of cytokeratin 18 (CK18), alpha fetoprotein (AFP), and CYP3A4 were measured using Western blot. The glycogen storing ability of the cells was detected by periodic acid-schiff (PAS) staining. Furthermore, the synthesis of albumin (ALB) and blood urea nitrogen (BUN) was measured. RESULTS: In experimental group, after 1 day of induction, the stem cells of fusiform shape began to lose sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with round and irregular shape at 7 days. Positive expressions of AFP, CK18, and CYP3A4 were observed in the experimental group, but negative expression in the control group. The concentrations of BUN and ALB were (0.43 +/- 0.07) mmol/L and (8.08 +/- 0.41) ug/mL in the control group and were (2.52 +/- 0.20) mmol/L and (41.48 +/- 4.11) ug/mL in the experimental group, showing significant differences (t=24.160, P = 0.000; t = 19.810, P = 0.000). PAS staining results showed navy blue nucleus and lavender cytoplasm in the control group, but dark purple cell body and visible nucleus in the experimental group. CONCLUSION: HUCMSCs could differentiate into hepatocyte-like cells induced by rat fibrotic liver tissue extracts, which have hepatocyte biomarkers (AFP, CK18, and CYP3A4) and hepatocyte-specific functions of glycogen storage, urea production and ALB secretion, so they could partially replace the function of hepatocytes, that may be one of the therapeutic mechanisms of stem cell transplantation. PMID- 26540985 TI - [ISOLATION OF RAT PATELLAR TENDON STEM CELLS AND EFFECT OF MECHANICAL STRETCHING ON Sox-9 EXPRESSION]. AB - OBJECTIVE: To isolate the tendon stem cells (TSCs) from rat patellar tendon and to investigate the effect of mechanical stretching on the expression of Sox-9. METHODS: TSCs were isolated from Sprague Dawley rat (12 weeks old) patellar tendon by collagenase digestion and low density culture. The cell colony morphology and number were observed by crystal violet staining; the cell morphology was observed by inverted phase contrast microscope, and the immunophenotypes of mesenchymal stem cells (MSCs) were determined by flow cytometry. The TSCs at passage 3 was given the mechanical stretching at 4%, 0.17 Hz for 4 hours and 24 hours in the experimental group, and cells without stretching was used as control. The Sox-9 gene and protein expressions were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: Primary cells showed clonal growth and star shape; after subculture, cells at passage 1 showed fibroblast-like shape. The cells formed cell colonies after 7 days; the expressions were positive for CD29, CD44, and CD90 and negative for CD45. The result of real-time fluorescence quantitative PCR showed that Sox-9 gene was down-regulated at 4 hours after mechanical stretching compared with control (P < 0.05), and up-regulated at 24 hours after mechanical stretching when compared with control group (P < 0.05). The result of Western blot showed that Sox-9 protein expression was lower at 4 hours after stretching, but higher at 24 hours after mechanical stretching than that in control group (P < 0.05). CONCLUSION: The rat patellar TSCs can be isolated successfully, and mechanical stretching inhibits the Sox-9 expression, but the inhibited effect might stimulate the Sox-9 expression after the mechanical stretching effect disappears. PMID- 26540986 TI - [EFFECT OF BONE MARROW MESENCHYMAL STEM CELLS ON GASTRIC ULCER REPAIRING]. AB - OBJECTIVE: To explore the ettect and mechanisms of bone marrow mesenchymal stem cells (BMSCs) on healing quality of acetic acid-induced gastric ulcer. METHODS: Forty-eight clean grade male Wistar rats were used to establish the model of gastric ulcer with acetic acid and were randomly divided into 3 groups after 3 days of modeling, 16 rats each group. After the abdominal cavity was open and stomach was pulled out, no treatment was given in group A, 150 uL phosphate buffered saline (PBS) and 150 uL BMSCs at passage 4+PBS (1 x 10(8) cells/100 uL) were injected into the gastric wall surrounding the ulcer at 5 different points in groups B and C respectively. After 10 days, the ulcer area was measured, the mucosal thickness and the number of dilated glands were tested in the regenerative mucosa by histological method. And the expression of vascular endothelial growth factor (VEGF) was detected at ulcerative margin by immunohistochemical method. RESULTS: The ulcer area in group C was significantly smaller than that of groups A and B (P < 0.01), but no significant difference was found between groups A and B (P > 0.05). HE staining showed that group C had thicker regenerative gastric mucosa, less dilated glands, and more regular mucosal structure than groups A and B, showing significant differences in regenerative gastric mucosa thickness and dilated glands number (P < 0.01), but no significant difference between groups A and B (P > 0.05). Immunohistochemical staining showed that the positive expression of VEGF in the ulcer margin mucosa of group C was significantly higher than that of groups A and B. The integral absorbance (IA) value of VEGF expression in group C was significantly higher than that in groups A and B (P < 0.01), but no significant difference between groups A and B (P > 0.05). CONCLUSION: BMSCs can accelerate ulcer healing by the secretion of VEGF, and improve the quality of ulcer healing. PMID- 26540987 TI - [A FOLLOW-UP STUDY ON AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS TRANSPLANTATION FOR CRITICAL LOWER ARTERIOSCLEROSIS OBLITERANS IN DIABETIC PATIENTS]. AB - OBJECTIVE: To assess the long-term effectiveness and safety of autologous bone marrow mononuclear cells (BM-MNC) transplantation in the treatment of critical diabetic lower arteriosclerosis obliterans (ASO). METHODS: Between January 2007 and January 2010, 61 patients with critical diabetic lower ASO were treated with standard medical therapies in 29 cases (control group) or with standard medical therapies and autologous BM-MNC transplantation in 32 cases (treatment group). There was no significant difference in gender, age, disease duration, Fontatine stage, glucose (GLU), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein-cholesterol (LDL-C), hemoglobin Alc (HbA1c), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between 2 groups (P > 0.05). The endpoints were overall survival (OS) and amputation-free survival (AFS). The risk indexes for ASO were observed and compared between 2 groups before and after treatments. RESULTS: The patients were followed up 2-36 months, and no malignant tumor occurred. The OS rate, OS time, AFS rate, and AFS time were 82.76% (24/29), (32.31 +/- 9.08) months, 37.50% (9/24), and (21.28 +/- 13.35) months in the control group and were 78.13% (25/32), (32.47 +/- 6.96) months, 68.00% (17/25), and (28.38 +/- 9.48) months in the treatment group; all indexes showed no significant differences (P > 0.05). OS rate, OS time, AFS rate, and AFS time showed no significant differences between 2 groups at the other time (P > 0.05) except AFS time at 1 year, which was significantly short in the control group than the treatment group (t = 2.806, P = 0.007). At the endpoint of follow-up, the indexes of GLU, TG, CHOL, LDL-C, HbAlc, SBP, and DBP showed no significant differences between before and after treatments and between 2 groups (P > 0.05) in 49 survival patients (24 in control group and 25 in treatment group). CONCLUSION: Autologous BM-MNC transplantation is safe and effective in the treatment of critical diabetic lower ASO, which can significantly improve AFS rate and prolong AFS time with no risks. PMID- 26540988 TI - [DEVELOPMENT PROGRESS OF MESENCHYMAL STEM CELLS SENESCENCE]. AB - OBJECTIVE: TO summarize the researcn situation or mesenchymal stem cells (MSCs) senescence, including the characteristics and mechanisms of senescence. METHODS: The original articles in recent years about MSCs senescence were extensively reviewed, and comprehensively analyzed. RESULTS: The senescence of MSCs which manifests as morphological senescence, reduced proliferation and differentiation potential, altered immunoregulation are found during the cultivation in experiment, which profoundly affects clinical application of MSCs. The research about the mechanisms of MSCs senescence includes telomere and telomerase, and stress-mediated injury etc, involving regulation of telomerase, and regulation of signal pathways of p53/p21, P13K/Akt, and Wnt/beta-catenin etc. CONCLUSION: The further study of senescence mechanisms will help to accelerate the clinical application of MSCs in the future. PMID- 26540989 TI - [RESEARCH DEVELOPMENT OF REVERSE TOTAL SHOULDER ARTHROPLASTY]. AB - OBJECTIVE: To investigate the development and clinical application of the reverse total shoulder arthroplasty. METHODS: The relative publications on reverse total shoulder arthroplasties were extensively reviewed and analyzed. RESULTS: Reverse total shoulder arthroplasty has extensive indications, especially for pseudoparalysis caused by irrepairable rotator cuff tears with forward or upper shift of the humeral head and intact function of deltoid. The clinical research results indicate that the short-term results are satisfactory, but there are some special complications, such as scapular nothching, instability and limities of internal and external rotation. While performing this kind of operation, the selection of the approach, the determination of the prosthetic rotation center should be considered well, and the bone graft should be paid attention to when the bony defect of the glenoid and proximal humerus exists. CONCLUSION: The using time of the reverse total shoulder arthroplasty is short, so the long-term results should be observed. The development of computer assisted technique is hopeful to be improve the results of the reverse total shoulder arthroplasty. PMID- 26540990 TI - [RESEARCH PROGRESS OF STRATEGIES TO AUGMENT TENDON-TO-BONE HEALING]. AB - OBJECTIVE: To summarize the application status and progress of the strategies to augment tendon-to-bone healing. METHODS: The present researches focused on augmentation of tendon-to-bone healing were extensively reviewed. RESULTS: The present strategies to augment healing of tendon-to-bone by enhancing the location environment, and increasing the cell numbers and relative growth factor. The mainly strategies include using calcium phosphate materials, biocompatible scaffolds and glue, growth factors, cell matrix, platelet-rich plasma, and periosteum. Although periosteum have been used in clinical and got some possitive effects, the others still not be used in clinical and needs further studies. CONCLUSION: There are many strategies to enhance the ability of tendon-to-bone healing, which got some positive results, but results of studies were varied. Thus, further fundamental research and clinical studies are required to achieve the best effects. PMID- 26540991 TI - [Arterial hypertension in the era of environmental concern and the internet]. PMID- 26540992 TI - [Screening and management of hypertension in elderly]. AB - The prevalence of hypertension in elderly is extremely high. Because of the burden of ageing of population, this condition considered as the most important risk factor for mortality is supposed to increase. There are some specific pitfalls in the diagnosis and management of hypertension in elderly. The definition of hypertension is the same in all age groups, however the phenotype is different in the elderly: white coat effect, non-dipping pattern, orthostatic hypotension, dysautonomia and pseudohypertension. The hallmark of hypertension in the elderly is pure systolic hypertension and an increased variability of blood pressure. The diagnosis is often difficult to establish. The elderly can be overtreated with undesirable effects of falls or hypoperfusion, particularly when there is frailty, or polymedication. PMID- 26540993 TI - [Should hypertensive patients adapt their antihypertensive drugs during high altitude exposure?]. AB - High altitude exposure during leisure time is becoming more and more frequent. Due to the high prevalence of hypertension in the general population, high altitude exposure in hypertensive patients may not be uncommon. The increase in blood pressure with altitude has been confirmed by ambulatory blood pressure measurement in normotensive as well as in hypertensive patients. Compared to a placebo, most hypertensive drugs keep their blood pressure lowering effect up to a certain altitude. It is recommended that hypertensive patients measure their blood pressure during high altitude, exposure and plan a possible adaptation of treatment with their physician before their sojourn. PMID- 26540994 TI - [Shift work and night work: what effect on blood pressure?]. AB - Shift work has become more and more common for the last thirty years. By definition, shift work disturbs the circadian rhythm and the internal clock. Even if the pathophysiological mechanisms are not well understood, a greater cardiovascular risk has been attributed to shift work. Cross-sectional and cohort studies have identified an association between shift work and an elevated blood pressure. Shift workers also present a higher incidence of hypertension and progression than day workers. Unfortunately, the heterogeneity of the studies, the multiple confounding factors, as well as the complexity to achieve a suitable comparison group make it impossible to draw firm clinical evidence. Nevertheless, this population needs a medical follow-up focused on the cardiovascular risks and blood pressure. PMID- 26540995 TI - [Atypical presentation of preeclampsia]. AB - Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia. PMID- 26540996 TI - [Innovative instruction for assisting patients with arterial hypertension]. AB - The MOOC In The Heart of Hypertension is an innovative online training for students and health providers. Its aim is to strengthen skills for professionals caring people suffering from hypertension. A MOOC is a free online training aiming unlimited participation. It widely promotes a high quality education. Medical and paramedical training recently seized upon this powerful tool, for initial and continuing training. Indeed, MOOC responds to several pedagogic challenges, particularly through educational strategies focused on the learner's skills: mastery of pedagogy, retrieval practice and peer grading. This MOOC about hypertension aims at responding to the needs of caregivers to enhance their therapeutic support skills. PMID- 26540997 TI - [Proton pump inhibitors (PPI): may be not as harmless as believed]. AB - Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is increasing. Their efficiency has been proven and the short term tolerance is good with few reversible side effects. However concerns about possible long term side effects continue to arise. This article reviews proven and potential side effects associated with PPI especially on the long term use. PMID- 26540998 TI - [The obverse and reverse of how to assist the terminally ill?]. PMID- 26540999 TI - [Baclofen: when does one know the scientific truth about its effectiveness in alcoholic disease?]. PMID- 26541000 TI - [The patient of bed No. 3]. PMID- 26541002 TI - [Lung cancer screening in smokers: paradoxical effects on motivation to quit smoking?]. PMID- 26541001 TI - [Oliver Sacks (1933-2015). An English physician who was able to explain neurology to the entire world]. PMID- 26541003 TI - [Association between alcohol consumption and risk of different types of breast cancer]. PMID- 26541004 TI - ["Five colors to eat better": a nice French example of a bad "good idea"]. PMID- 26541005 TI - [Sleep . . . that stranger]. PMID- 26541006 TI - Position Statement. Deceased Organ and Tissue Donation. PMID- 26541007 TI - Atrial electrogram interpretation improves after an innovative education program. AB - BACKGROUND: To avoid adverse patient outcomes from inappropriate treatment, it is recommended that an atrial electrogram (AEG) be recorded whenever atrial arrhythmias develop in patients after cardiac surgery. However, AEGs are not commonly performed because nurses lack knowledge about differentiating atrial rhythms on AEGs. OBJECTIVE: To investigate whether completing a novel online evidence-based education program on interpreting AEGs would improve critical care nurses' AEG interpretation. METHODS: Specialized critical care nurses were taught about obtaining and interpreting atrial rhythms on AEGs using a 42-minute online mini-movie. AEG interpretation was assessed pre and two and eight weeks post intervention. RESULTS: AEG interpretation increased two weeks post intervention and was retained at eight weeks. Some participants used this newly acquired knowledge to interpret arrhythmias that were not taught during the education program. CONCLUSION: Accurate interpretation of AEGs is an easy skill for specialized critical care nurses to learn via an online education program. PMID- 26541009 TI - [Lyne Cloutier]. PMID- 26541010 TI - [A network under the sign of change]. PMID- 26541008 TI - A social construction of the development of ICU nursing in Canada, 1960 to 2002. AB - BACKGROUND: The early 1960s marked the opening of intensive care units (ICUs) in several hospitals across Canada. From the beginning, registered nurses constituted the largest body of health care providers in the ICU environment and they were the central provider of hands-on care to patients and families. From a historical perspective, however, a limited body of knowledge exists specific to the development of ICU nursing in Canada. PURPOSE: In this study we explored the development of ICU nursing in Canada from 1960 to 2002 using a social history approach that emphasized the creation of an historical account from the perspective of the everyday experiences of ICU nurses. METHOD: A social history approach was used. Primary sources included oral history interviews, documents and records, published professional literature between 1960 and 2002, as well as photographs. The study received ethics approval from the research ethics boards at the University of Ottawa (for conducting oral history interviews), as well as Queen's University (for access to archives at the Kingston General Hospital). RESULTS: The findings of this study provide a perspective on how ICU nurses learned and created new knowledge, as well as the establishment of an ICU nursing identity at both the individual and national levels. PMID- 26541011 TI - [Myths and realities about the holding of immunization records]. PMID- 26541012 TI - [Monteregie: Assessing the risk of suicide]. PMID- 26541014 TI - [Alcohol abuse by seniors]. PMID- 26541013 TI - [Difficult personalities and relational troubles?]. PMID- 26541015 TI - [Care of spinal cord injures in acute phase: online training modules]. PMID- 26541016 TI - [Address of the Secretary General: the international nursing network of French language]. PMID- 26541018 TI - [Belgium: patient empowerment]. PMID- 26541017 TI - [Prevention: the nursing role]. PMID- 26541019 TI - [Symposium on the quality of care and patient safety]. PMID- 26541020 TI - [Measuring quality: standardize to understand one another]. PMID- 26541021 TI - [Africa: security after Ebola]. PMID- 26541022 TI - [Quality of nursing program: the urgency to act]. PMID- 26541023 TI - [Quality of care and patient safety: A challenge]. PMID- 26541024 TI - [Forum on the emergence of tomorrow's leaders]. PMID- 26541025 TI - [Bariatric surgeries. The stages and the benefits]. PMID- 26541026 TI - [Total Arthroplasty of the knee part 1. Anesthetic approaches]. PMID- 26541027 TI - [The PROMOVAC study]. PMID- 26541028 TI - [Toxoplasma gondii infection in an imported case of falciparumn malaria]. PMID- 26541029 TI - [Construction of Eukaryotic Expression Vector Containing ROP18-ROP12 of Toxoplasma gondii RH Strain]. AB - OBJECTIVE: To construct a recombinant eukaryotic expression plasmid containing ROP18-ROP12 (encoding rhoptry protein 18 and 12) complex gene of Toxoplasma gondii, and examine its expression in eukaryotic cells. METHODS: Recombinant plasmids pVAX1-ROP18 and pVAX1-ROP12 were digested by restriction enzymes BamH I and Xba I . ROP12 gene was cloned into pVAX1-ROP18 to construct the eukaryotic expression plasmid pVAX1-ROP18- ROP12. After colony PCR, enzyme digestion and sequencing, the correct recombinant plasmid pVAX1-ROP18-ROP12 was transfected into HeLa cells. Along with it were groups of empty plasmid, pVAX1-ROP18 and pVAX1-ROP12. Total RNA was extracted from HeLa cells and reverse-transcribed to cDNA. RT-PCR was performed to evaluate mRNA expression of the housekeeping gene beta-actin and ROP18-ROP12 complex gene. Immunofluorescence assay and Western blotting were performed to determine the protein levels of ROP18-ROP12 fusion protein. RESULTS: Colony PCR in recombinant plasmid pVAX1-ROP18-ROP12 showed a specific band at about 2 373 bp, consistent with expectation. The extracted recombinant plasmids were confirmed by Hind III, BamH I and Xba I digestion. Sequencing results showed that the sequence of pVAX1-ROP18-ROP12 was 100% identical to that of T. gondii RH strain ROP18 gene (Accession No. AM075204.1) and 99% identical to that of T. gondii RH strain ROP12 gene (Accession No. DQ096559.1). Further, RT-PCR showed amplification products at 613 bp for beta actin in all the groups, while only the pVAX1-ROP18-ROP12 transfection group showed amplification products for the ROP18-ROP12 complex at 2,373 bp. In addition, the indirect immunofluorescence assay showed yellow-green fluorescence in HeLa cells transfected with pVAX1-ROP18-ROP12, but not in control cells. Western blotting showed that the ROP18-ROP12 fusion protein was expressed in HeLa cells transfected with recombinant plasmid pVAX1-ROP18-ROP12. CONCLUSIONS: The recombinant eukaryotic plasmid pVAX1-ROP18-ROP-2 is constructed and can be expressed in eukaryotic system. PMID- 26541030 TI - [Gallbladder Stone Types in Patients with Cholelithiasis and Clonorchis sinensis Infection in the Endemic Area of Clonorchiasis]. AB - OBJECTIVE: To investigate the relationship between Clonorchis sinensis infection and the gallbladder stone type in patients with cholelithiasis in the endemic area of clonorchiasis. METHODS: Gallbladder stones were collected from 598 patients with cholelithiasis through minimally invasive gallbladder-preserving cholelithotomy in the Sixth People's Hospital of Nansha District from May 2009 to October 2012. The stone samples were analyzed for composition by Fourier transform infrared spectroscopy to identify their types. The Clonorchis sinensis eggs were detected in the stones by microscopic examination, and the detection rates of eggs were calculated for different stone types. Then the clinical characteristics and biochemical indicators were compared among patients with different types of stones, as well as between Clonorchis sinensis egg-positive and -negative patients with the calcium-carbonate type of stones. Some calcium carbonate stones positive for Clonorchis sinensis eggs were randomly selected for further scanning electron microscopy (SEM) examination. RESULTS: Of the stones from 598 patients, 234 (39.1%) were cholesterol type, 133 (22.2%) bile pigment type, 112(18.7%) calcium-carbonate type, 86 (14.4%) mixed types and 33(5.5%) were others. The detection rate of Clonorchis sinensis eggs in these types was 6% (15/234), 44% (59/133), 60% (67/112), 36% (31/ 86) and 30% (10/33), respectively, being highest in calcium-carbonate stones while lowest in cholesterol stones. The Co2-combining power of the plasma was higher in patients with calcium-carbonate and mixed stones than in those with cholesterol stones (P < 0.05), and the CO2 combining power of the bile and biliary pH were both higher in patients with calcium-carbonate types than in those with other types (P < 0.05). In addition, in patients with calcium-carbonate stones, the CO2-combining powers of the plasma and the bile, as well as biliary pH were all higher in the egg-positives than in the egg-negatives. Further, both light microscopy and SEM revealed adherence of the Clonorchis sinensis eggs to calcium-carbonate crystals. CONCLUSION: The infection rate of Clonorchis sinensis is higher in patients with calcium carbonate gallbladder stones than in those with other types of stones. PMID- 26541031 TI - [Prokaryotic Expression and Immunoreactivity Analysis of alpha-8 Giardin in Giardia lamblia]. AB - OBJECTIVE: To clone and express alpha8-giardin gene of Giardia lamblia, and analyze its immunoreactivity. METHODS: The open reading frame (ORF) of alpha8 giardin gene was amplified by PCR. The PCR product was cloned into prokaryotic expression vector pET-30a (+) with restriction enzymes EcoR I and Xho I . The recombinant vector pET30a (+)-alpha8-giardin was transformed into E. coli BL21 (DE3), and the positive clones were then selected. The constructed pET30 a (+) alpha8-giardin was induced with IPTG for expression, and purified through Ni affinity chromatography. The recombinant protein was examined by SDS-PAGE and Western blotting. RESULTS: The length of alpha8-giardin gene was 930 bp. PCR and restriction enzyme digestion analysis confirmed the construction of recombinant plasmid pET30a (+)-alpha8-giardin. SDS-PAGE and Western blotting analysis showed that the recombinant protein rGiardin (about M, 36,000) was expressed in E. coli as inclusion body protein, and reacted positively with anti-His tag antibody and rabbit anti-G. lamblia serum. CONCLUSION: The recombinant plasmid pET30a (+) alpha8-giardin is constructed, and the purified rGiardin protein shows immunoreactivity. PMID- 26541032 TI - [Establishment of Duplex PCR for Identifying Metagonimus yokogawai and Haplorchis taichui]. AB - OBJECTIVE: To develop a duplex PCR method for identifying Metagonimus yokogawai and Haplorchis taichui. METHODS: ITS1 sequences of M. yokogawai and H. taichui, as well as those of their homologous species were obtained from GenBank, and two sets of specific primer pairs for M. yokogawai and H. taichui were designed accordingly using Primer Premier 5.0 software. PCR reaction system and conditions were optimized. The established duplex PCR method was applied in a pool of M. yokogawai, H. taichui, and 17 related species to examine its specificity. Sensitivity was evaluated through serial dilutions of plasmids containing their specific sequences. Finally, the duplex PCR was applied to identify M. yokogawai and H. taichui among trematodes collected from the viscera of 47 cats and 40 dogs to test its practicality. RESULTS: The duplex PCR method amplified target sequences of M. yokogawai and H. taichui, generating 648 bp and 279 bp products, respectively. No cross reaction was found with the following 17 related species: Haplorchis pumilio, Clonorchis sinensis, Pharyngostomum cordatum, the metacercaria of Metorchis sp. and Exorchis sp., Echinochasmus liliputanus, Echinochasmus perfoliatus, Echinostoma friedi, Hypoderaeum conoideum, Holostephanus sp., Diplodiscus sp., Anisakis sp., Metorchis orientais, Paragonimus westermani, Watsonius watsoni, Notocotylus sp. and Hysterothylacium sp, indicating a high specificity of this method. The detection limits for DNAs of M. yokogawai and H. taichui were 1.49 x 10(-1) pg and 1.14 x 10(-1) pg, suggesting a good sensitivity for this method. Further, the duplex PCR successfully identified M. yokogawai and H. taichui from cat and dog viscera, with no cross amplification of other trematodes. CONCLUSION: The duplex PCR is effective in identifying Metagonimus yokogawai and Haplorchis taichui. PMID- 26541033 TI - [Observation on the Histologic Structure of Multiceps multiceps in Artificially Infected Dogs]. AB - OBJECTIVE: To observe the microstructure and ultrastructure of Multiceps multiceps from the artificially infected dogs. METHEDS: Two male dogs were infected with the coenurus of M. multiceps from naturally-infected sheep (about 80-100 per dog). The adult worms of M. multiceps were recovered from the intestine, and fixed by the conventional method. The scolex, neck, immature proglottid, mature proglottid, and gravid proglottid were prepared for paraffin section and ultrathin sections with HE staining and uranyl acetate staining, and observed under light microscope and electron transmission microscope, respectively. RESULTS: Under light microscope, each proglottid consisted of cortical layer and parenchymal layer. The cortical layer was composed of microvilli, syncytium, and substrate layer. The parenchymal layer mainly consisted of muscle tissue, excretory system, and reproductive system. The microvilli layer of scolex was thinner than that of neck and mature proglottid, and the longest microvilli were mainly distributed in the binding site between the proglottids. The scolex was extremely muscular. The nervous system and excretory system were repeated in each proglottid. Mature proglottid had both male and female reproductive systems. Gravid proglottid had uterus and egg, and atrophic male reproductive organs. CONCLUSION: The special microstructure of Multiceps multiceps are that most microvilli in the cortex is cylindrical; the microvilli length in the binding sites between mature proglottids is longer than that of other parts. PMID- 26541034 TI - [Effect of Crude Antigens from Ascaris lumbricoides on the Apoptosis and Secretion of IL-6 and TGF-beta of Human Lung Adenocarcinoma Cells]. AB - OBJECTIVE: To investigate the effect of crude antigens of Ascaris lumbricoides on the secretion of IL-6 and TGF-beta of human lung adenocarcinoma cells (A549 cells), and the apoptosis of A549 cells. METHODS: Crude antigens of A. lumbricoides were prepared. A549 cells were co-cultured with 25, 125, and 500 ug/ml crude antigens of A. lumbricoides for 1, 18, and 24 h, named as low concentration group, medium concentration group, and high concentration group, respectively. Meanwhile, A549 cells were co-cultured with culture medium (negative control) and 12.5 ug/ml adriamycin (positive control). The apoptosis rate was detected by using Annexin V-FITC apoptosis detection kit. The cell changes were determined by flow cytometry. The levels of mRNA expression of IL-6 and TGF-beta were detected by ELISA and real time PCR, respectively. RESULTS: The apoptosis rate of A549 cells induced by crude antigens for 1, 18, and 24 h was significantly higher than that of negative control (P < 0.01). The apoptosis rate in medium concentration group (treated for 18 h) was highest [(47.10 +/- 3.68)%]. After co-culture with 125 ug/ml crude antigens for 18 h, the proportion of G0/G1 phase cells increased and that of S phase cells decreased, and there was a significant difference between medium concentration group and negative control group. At the same time, the level of IL-6 increased with the increasing concentration of crude antigens. However, no significant difference was found in the level of TGF-beta among the groups. In the medium concentration group, mRNA expression levels of IL-6 (5.95 +/- 0.31) and TGF-beta (3.43 +/- 0.35) of A549 cells reached peak on the 18th hour, and were significantly higher than that of the control (P < 0.01). CONCLUSION: The cell cycle of A549 cells is blocked in G0/G1 phase induced by crude antigens of A. lumbricoides. And the apoptosis may be related to the changes in the level of TGF-beta and IL-6. PMID- 26541035 TI - [Quality Analysis of Laboratory Malaria Diagnosis in Yunnan Province during 2012 2014]. AB - OBJECTIVE: To assess the quality of microscopy-based malaria diagnosis in Yunnan Province from August 2012 to October 2014, and analyze the relevant factors. METHODS: Blood samples were collected from patients diagnosed as malaria by microscopy in county-level laboratories of Yunnan Province. The blood smears and blood filter paper samples were prepared and submitted to the provincial malaria diagnosis reference laboratory for further confirmation by both microscopy and the genetic approach. Coincidence rates for species identification between county and provincial laboratories were analyzed using the SPSS 21.0 software. RESULTS: From August 2012 to October 2014, 1 400 malaria cases were diagnosed with microscopy in 72 counties of Yunnan Province. Among them, the cases of falciparum malaria, vivax malaria, and unclassified malaria accounted for 18.4% (252/1,400), 79.3% (1,105/1,400) and 3.1% (43/1,400), respectively. The percentage of unclassified malaria cases reached a peak in 2012 (3.5%, 9/257). The coincidence rate for species identification with microscopy between county-level and provincial-level laboratories was 70.1% (845/1,216) in 2012, being the lowest during 2012-2014, and the coincidence rate for diagnosis of positive infection was 77.6% (943/1,216). Similarly, the coincidence rates for species identification and for positive infection between county-level laboratories using microscopy and the provincial-level laboratory using the genetic approach were 81.3% (150/185) and 85.0% (157/185) respectively in 2012, being also the lowest during 2012-2014. In the provincial laboratory, the inconsistency rate for species identification between microscopy and the genetic approach was 8.7% (97/1 120), predominately the infection-negative results by microscopy versus falciparum malaria, vivax malaria or mixed infection revealed by the genetic approach (57.7%, 56/97). The sampling coverage rate in counties was the lowest in November 2012 (46.9%, 82/175). The blood smear preparation scored 69.8, 70.4 and 78.8 (P < 0.05) in 2012, 2013 and 2014, respectively. CONCLUSION: The quality of laboratory malaria diagnosis has been significantly improved in most counties of Yunnan Province since 2013. PMID- 26541036 TI - [Assessment of Antimalarial Activity of Choline Derivatives against Plasmodium falciparum Growth in vitro by SYBR Green I Method]. AB - OBJECTIVE: To investigate the antimalarial activity of four choline derivatives against Plasmodium falciparum 3D7 strain growth in vitro. METHODS: Four choline derivatives MD [N-dodecyl-N-(2-hydroxyethyl)-N,N- dimethyl ammonium bromide], ED [N-dodecyl-N-(2-hydroxyethyl)-N,N-diethyl ammonium bromide], MT [N-tetradecyl-N- (2-hydroxyethyl)-N,N-dimethyl ammonium bromide], and ET [N-tetradecyl-N-(2 hydroxyethyl)-N,N-diethyl ammonium bromide] were dissolved separately in DMSO at serial concentrations (1-10(5) umol/L). The solutions were diluted by 1,000-fold with RPMI 1640 medium. 20 ul drug-containing medium and 80 ul P. falciparum infected erythrocyte suspension (2% final hematocrit and 0.3%-0.5% parasitemia) were added to each well of microtiter plates. Drug effect on the in vitro growth of P. falciparum was measured by SYBR Green I method. The half maximal inhibitory concentration (IC50) was calculated from dose-response curves. Artemisinine served as positive control. RESULTS: Artemisinine, MD, ED, MT, and ET showed different degrees of dose-dependent inhibition on P. falciparum growth. When the MD concentration was above 10 nmol/L, the inhibition rate increased significantly. Both ED and ET showed significant inhibitory effects at high concentrations, with inhibition rate of > 95% when their doses were > 10(4) nmol/L. The IC50 values of MD, ED, MT, and ET were 1 620, 33.9, 116, and 68.9 nmol/L, respectively, all significantly higher than that of artemisinine (5.7 nmol/L) (P < 0.05). CONCLUSION: The four choline derivatives show certain antimalarial activity, which is lower than that of artemisinine. Among the four derivatives, ED has the strongest antimalarial activity against P. falciparum 3D7 strain. PMID- 26541037 TI - [Single-tube Single-run Multiplex PCR Detects Mixed Samples with Four Species of Plasmodium]. AB - OBJECTIVE: To establish a single-tube single-run multiplex PCR technique that can detect single or mixed samples with four species of Plasmodium. METHODS: Folding primers were designed based on the fast nested PCR. The reaction component concentrations were optimized and the primers were selected based on the annealing temperature. The established single-tube single-run folding-primer multiplex PCR (FP-PCR) was tested for its sensitivity and specificity to detect single-species and mixed samples with P. vivax, P. falciparum, P. ovale (including P. ovale wallikeri) and/or P. malariae. RESULTS: In all the seven experimental repeats, FP-PCR successfully detected single-species infection for all the four species, with the detection limit reaching or close to 1 parasite/ul blood. For mixed infections with 2-4 species at different densities with the highest being 100 times of the lowest, FP-PCR identified all the species in each combination in 57 out of 84 tests. Further, in 10 dried blood samples on filter paper from healthy subjects, no FP-PCR amplification was found, except weak formation of dimers. CONCLUSION: FP-PCR is a simple and sensitive method for detecting both single-species and mixed infections with human Plasmodium, and can be applied for malaria diagnosis, screening and monitoring. PMID- 26541038 TI - [Epidemiological Analysis of Malaria in Wenzhou City during 2007-2014]. AB - A total of 258 malaria cases with 2 deaths were reported during 2007-2014, including 148 vivax malaria cases, 106 falciparum malaria cases, and 4 ovale malaria cases. During 2007-2009, 86.0% (135/157) were vivax malaria cases with 3 indigenous cases. In 2010-2014, the proportion of falciparum malaria is increasing year by year, and all were imported cases. 98.8% were imported from Africa and other provinces in China. Most cases occurred among patients aged 20 49 years, and the male-to-female ratio was 3.16:1. Most patients were workers and commercial service personnel. The malaria epidemic situation is relatively stable in Wenzhou. Malaria control and elimination interventions should emphasize the monitoring and education of transient population to control the imported cases, and explore multi-sector coordination for malaria prevention and control. PMID- 26541039 TI - [A Retrospective Analysis on the Prevalence of Visceral Leishmaniasis in Gansu Province during 2005-2014]. AB - OBJECTIVE: To review the prevalence of visceral leishmaniasis in Gansu Province during 2005-2014. METHODS: The data of visceral leishmaniasis cases in Gansu Province during 2005-2014 were collected and descriptive statistical analysis was performed. RESULTS: During 2005-2014, 1,260 cases of visceral leishmaniasis were reported in Gansu Province. The incidence showed a trend of annual increase from 2005 (90 cases, 7.14%) onwards, peaked in 2011 (168 cases, 13.33%), and decreased afterwards. In 2014, 85 cases (6.75%) were reported. Most of the cases were from the Longnan region and some areas in Gannan Tibetan Autonomous Prefecture. Specifically, the case number was highest in Wudu District of the Longnan region (506/1,260, 40.16%), followed by Wenxian County (302/1,260, 23.97%) and Zhouqu County (202/1,260, 16.03%). In total, the cases had a male-to-female ratio of 1.46:1, and concentrated in age group of 0-5 years (665/1,260, 52.78%), showing a trend of decrease with age increase. In addition, visceral leishmaniasis occured throughout the year, with a higher cumulative incidence from March to June [10.48% (132/1,260), 13.33% (168/1,260), 12.86% (162/1,260) and 11.67% (147/1,260), respectively]. CONCLUSION: From 2005 to 2014, the Longnan region and some areas of Gannan Prefecture are the major endemic areas of visceral leishmaniasis, with more cases in children under 5 and higher incidence from March to June. PMID- 26541040 TI - [The Application of Gold-immunochromatographic Test Strip Reader in Serum Antibody Detection in Echinococcosis]. AB - One hundred and fifty-nine serum samples from hydatid disease patients and 80 serum samples from patients with other liver diseases were detected by gold immunochromatographic assay, and read by naked eyes and the gold immunochromatographic test strip reader. The sensitivity, specificity, and accuracy of eye-based method was 92.4% (147/159), 85.0% (68/80), and 89.9% (215/239), which was lower than that of the reader detection (95.6%, 93.7%, 95.0%, respectively). While, its false negative rate (7.5%, 12/159) and false positive rate (15.0%, 12/80) was higher than that of the reader detection (4.4% and 6.3%, respectively). PMID- 26541041 TI - [Research Advances on Toxoplasma gondii Proteomics]. AB - The proteomic techniques have been widely used in Toxoplasma gondii research since the past decade, providing proteomic data that facilitate understanding of T. gondii activities. Currently, the global proteomic studies of T. gondii are mainly confined to the tachyzoite and the oocyst stages. The subproteomic research involves some important antigens, such as the soluble tachyzoite antigen, glycoproteins, and immunoproteins, etc. The differential proteomics of T. gondii is mainly focused on identifying differentially-expressed proteins in different T. gondii strains. This review summarizes the current status of proteomic research on T. gondii, with specific focuses on global proteomic, subproteomic, and differential proteomic findings. In addition, this review gives an overview on web-based resources that provide proteomic data and support for studies on T. gondii, and finally discusses future prospects of T. gondii proteomics applications. PMID- 26541042 TI - [Implementation Situation and Application Evaluation of "Standards for Control and Elimination of Malaria"]. AB - The application evaluation of "Standards for Control and Elimination of Malaria" was carried out in 11 epidemic provinces/autonomous regions by questionnaires, field investigation and special interviews from January to May, 2014. Two hundred and forty questionnaires were completed by the personnel from the health administrations and the institutions of disease control and prevention. The questionnaire response rate was 84% (240/285). Totally 90% participants had known and used this standards. In detail, managers from the health administration departments had a percent of 100.0% (26/26), while professionals in the institutions of disease control and prevention had a percent of 88.8% (190/214). In malaria-endemic provinces/autonomous regions/municipalities, 18 training classes of malaria control and prevention were held from January 2012 to December 2013. This standards was one of the main contents. One hundred and fifty-two pieces of suggestion and recommendation were obtained, with 84.2% (128/152) relating to personnel and supporting conditions, and 15.8% (24/152) on technical issues. PMID- 26541043 TI - [Research Advance on Toxoplasma gondii Rhoptry Protein 2 Family as Candidate Vaccine Molecules]. AB - Toxoplasma gondii rhoptry protein 2 family (ROP2 family), secreted by the rhoptry, plays an important role in T. gondii invasion of host cells and its virulence. The ROP2 family members include ROP2, ROP4, ROP5, ROP8, ROP13, ROP16, ROP17, and ROP18. Recent studies have found that these members are potential vaccine candidates against toxoplasmosis, and can induce the protective immunity of the host. This paper reviews the research advance on the ROP2 family members as DNA or protein vaccines against toxoplasmosis. PMID- 26541044 TI - [A child case of cerebral sparganosis]. PMID- 26541045 TI - [The Immunomodulatory Role of C-type Lectin Receptors in Parasitic Infection]. AB - C-type lectins are a group of Ca(2+)-dependent glycan-binding proteins. The C type lectin receptors (CLRs) recognize carbohydrate ligands in a Ca(2+)-dependent manner. Recent research has demonstrated that CLRs could recognize glycoproteins and activate downstream immune responses. This review summarizes the roles of several CLRs in parasitic infection. PMID- 26541046 TI - [Excystation Time and Location of Metacercariae of Clonorchis sinensis in Mice]. AB - Metacercariae of Clonorchis sinensis (20 per mouse) were given orally to Kunming mice. The mice were sacrificed at 0.5, 1, 2, 4, 8, 16, 32, and 64 h after infection. The results showed that the excystation of the metacercariae occurred in the stomach and small intestine, mainly in the duodenum. Excystation occurred mainly at 2, 4, 8, and 16 h post-infection. Juveniles were found in hepatic duct on 0.5 h post-infection. The number of juveniles increased with the extension of infection time, which kept unchanged in hepatic duct from 32 h after infection. PMID- 26541047 TI - [Screening of Molluscacidal Microorganisms against Oncomelania hupensis and Their Effect]. AB - Fifteen soil samples were collected from Oncomelania hupensis culture pond in Miluo Schistosomiasis Control and Prevention Base, Hunan Province. Four strains of bacteria were identified to have molluscacidal effects, numbered as B8, B27, B36 and B59. Compared with the fermentation broth groups and bacteria suspension groups, the fermentation supernatant groups of the four strains showed the strongest molluscacidal effect. The fermentation supernatant of B59 strain showed the best molluscacidal effect, with snail mortalit of 73.3% and 96.7% at 48 h and 72 h of treatment, respectively. SDS-PAGE revealed no proteins in fermentation supernatant, fermentation broth and bacteria suspension of B59 strain. Molecular phylogenetic analysis based on ITS sequence showed that the ITS sequence of strain B59 (accession No. KP146144) was 100% homologous to that of the same fragment of Bacillus cereus (accession No. CP001746). PMID- 26541048 TI - [Killing Effect of Carpesium abrotanoides on Taenia asiatica Cysticercus]. AB - The cysticerci of Taenia asiatica were cultured in vitro with different concentrations of water decoction of Carpesium abrotanoides (20, 40, and 60 mg/ml). The killing effect of C. abrotanoides on T. asiatica and the morphological change of cysticerci were observed under microscope 24 hours post culture. The water decoction of C. abrotanoides showed significant killing effect on the cysticerci. The mortality of the parasites(95.0%, 57/60) was highest in 60 mg/ml group. The dead body of cysticercus shows shrunken with the enlarged scolex, and sucker tissue degenerated. PMID- 26541049 TI - [Seroepidemiological Survey on Echinococcosis among Children in Ningxia Hui Autonomous Region in 2012]. AB - According to the population structure, a stratified cluster sampling was carried out in 22 counties/ cities/disticts of Ningxia Hui Autonomous Region from June to August 2012. Serum anti-echinococcus IgG was detected by ELISA. Among 22995 sampled children from 91 primary schools, the sero-positive rate was 2.9%. The rate in males and females was 2.8%(333/11 840) and 3.0%(337/11 155), respectively (chi2 = 0.88, P > 0.05). Higher serum positive rate occurred in Yuanzhou District (10.6%, 169/1602), Yanchi County (9.1%, 74/810), and Zhongning County (7.1%, 96/1350) (chi2 = 1826.51, P < 0.05). The rate in rural schools (3.1%, 371/11 963) was higher than that of urban ones (2.7%, 368/13,834) (chi2 = 4.30, P < 0.05), and higher in Hui nationality (3.3%, 302/9,127) than that of Han nationality (2.7%, 368/13,834) (chi2 = 8.17, P < 0.05). The highest positive rate was found in the group of 7 to 9 years (3.2%, 180/5 662) and of 12 years (3.3%, 254/7,694) (chi2 = 4.11, P < 0.05). PMID- 26541050 TI - [A case of Blastocystis hominis (subtype 3) infection confirmed by PCR and in vitro culture]. PMID- 26541051 TI - Differences in the Judged Direction of Gaze From Heads Imaged in 3-D versus 2-D. AB - Observers viewed a model imaged on an LCD monitor in 3-D or 2-D as she gazed at points along a horizontally oriented meter stick from a distance of 80 cm. Her head was either straight or turned 20 degrees to the side, and for each head orientation, her gaze was straight, 10 degrees, or 20 degrees to the side, with her eyes individually open, both open, or both closed. For images in which both eyes were closed, the observers pointed along the same meter stick to where they judged her head to be pointed. When one or both eyes were open they judged where she appeared to be gazing. Gaze from the 2-D images agreed with previous studies. A comparison of the results from the 2-D versus 3-D images showed that the judgments were virtually identical for gaze from the straight versus turned head in all combinations of straight versus averted gaze, eyes individually open versus both open. The judgments were also virtually identical for head point. This suggests that 2-D studies that have used procedures similar to those described in this study may be applied to real world 3-D gaze perception. PMID- 26541052 TI - Simultaneous Sketching Aids the Haptic Identification of Raised Line Drawings. AB - Haptically identifying raised line drawings is difficult. We investigated whether a major component of this difficulty lies in acquiring, integrating, and maintaining shape information from touch. Wijntjes, van Lienen, Verstijnen, and Kappers reported that drawings which participants had failed to identify by touch alone could often subsequently be named if they were sketched. Thus, people sometimes needed to externalize haptically acquired information by making a sketch in order to be able to use it. We extended Wijntjes et al.'s task and found that sketching while touching improved drawing identification even more than sketching after touching, but only if people could see their sketches. Our results suggest that the slow, serial nature of information acquisition seriously hampers the haptic identification of raised line drawings relative to visually identifying line drawings. Simultaneous sketching may aid identification by reducing the burden on working memory and by helping to guide haptic exploration. This conclusion is consistent with the finding reported by Lawson and Bracken that 3-D objects are much easier to identify haptically than raised line drawings since, unlike for vision, simultaneously extracting global shape information is much easier haptically for 3-D stimuli than for line drawings. PMID- 26541053 TI - Effect of Eye Height on Estimated Slopes of Hills. AB - Several studies have shown that slopes of hills are greatly overestimated. We have recently demonstrated that the overestimates increase logarithmically as the end point of the domain to be estimated is increased. A theoretical analysis showed that a critical parameter is the angle between the observer's line of sight and the slope of the hill, when the observer fixates the far point of the required domain. The theory predicts that increasing the observers' eye height will increase this angle, thus reducing the overestimates. Here, we test that theory by having observers stand on a box to increase their eye height. Slope estimates for various ranges again followed a logarithmic function, with lower estimates at nearer distances compared with other observers standing directly on the surface of the hill. At larger distances, slope estimates with and without increased eye height converged. PMID- 26541054 TI - Direction of Auditory Pitch-Change Influences Visual Search for Slope From Graphs. AB - Linear trend (slope) is important information conveyed by graphs. We investigated how sounds influenced slope detection in a visual search paradigm. Four bar graphs or scatter plots were presented on each trial. Participants looked for a positive-slope or a negative-slope target (in blocked trials), and responded to targets in a go or no-go fashion. For example, in a positive-slope-target block, the target graph displayed a positive slope while other graphs displayed negative slopes (a go trial), or all graphs displayed negative slopes (a no-go trial). When an ascending or descending sound was presented concurrently, ascending sounds slowed detection of negative-slope targets whereas descending sounds slowed detection of positive-slope targets. The sounds had no effect when they immediately preceded the visual search displays, suggesting that the results were due to crossmodal interaction rather than priming. The sounds also had no effect when targets were words describing slopes, such as "positive," "negative," "increasing," or "decreasing," suggesting that the results were unlikely due to semantic-level interactions. Manipulations of spatiotemporal similarity between sounds and graphs had little effect. These results suggest that ascending and descending sounds influence visual search for slope based on a general association between the direction of auditory pitch-change and visual linear trend. PMID- 26541055 TI - Frogs Jump Forward: Semantic Knowledge Influences the Perception of Element Motion in the Ternus Display. AB - The Ternus effect is a robust illusion of motion that produces element motion at short interstimulus intervals (ISIs; < 50 ms) and group motion at longer ISIs (> 50 ms). Previous research has shown that the nature of the stimuli (e.g., similarity, grouping), not just ISI, can influence the likelihood of perceiving element or group motion. We examined if semantic knowledge can also influence what type of illusory motion is perceived. In Experiment I, we used a modified Ternus display with pictures of frogs in a jump-ready pose facing forwards or backwards to the direction of illusory motion. Participants perceived more element motion with the forward-facing frogs and more group motion with the backward-facing frogs. Experiment 2 tested whether this effect would still occur with line drawings of frogs, or if a more life-like image was necessary. Experiment 3 tested whether this effect was due to visual asymmetries inherent in the jumping pose. Experiment 4 tested whether frogs in a "non-jumping," sedentary pose would replicate the original effect. These experiments elucidate the role of semantic knowledge in the Ternus effect. Prior knowledge of the movement of certain animate objects, in this case, frogs can also bias the perception of element or group motion. PMID- 26541056 TI - Stereo-Curvature Aftereffect Is Due to More Than Shape Curvature Adaptation. AB - For stereo-curvature aftereffect (sCAE), there is no agreement on whether adaptation occurs at the disparity-specified stage, the percept-specified stage, or both. Additionally, it remains uncertain whether retinal-position-dependent sCAE can be induced by possible adaptation to disparity-specified sources. Our study aimed to investigate the dependency and processing levels of adaptation underlying sCAE using dynamic spherical adaptation stimuli with static fixation. Experiment I examined the dependency by dynamically altering the location or size of adaptation stimuli. Experiment 2 investigated the adaptation levels via three sub-experiments: Experiment 2.1 examined how eccentricity influenced adaptation strength using static adaptation stimuli with different eccentricities, Experiment 2.2 tested a hypothesis about adaptation to a percept-specified primitive shape index (PSI) using dynamic size change of adaptation stimuli, and Experiment 2.3 tested another hypothesis on adapting disparity-specified average disparity information (ADI) using dynamic PSI change of adaptation stimuli. The results showed retinal-position-dependent and scale-independent sCAE. In addition to a possible eccentricity effect, the retinal-position dependence can result from ADI adaptation while the scale independence can be attributed to PSI adaptation. Therefore, sCAE is caused by adaptation at both the disparity specified and percept-specified stages. Additionally, sCAE endows two coexisting adaptation processes with one dependent on retinal position and one independent of retinal position. PMID- 26541057 TI - Self-Identification With Another's Body Alters Self-Other Face Distinction. AB - When looking into a mirror healthy humans usually clearly perceive their own face. Such an unambiguous face self-perception indicates that an individual has a discrete facial self- representation and thereby the involvement of a self-other face distinction mechanism. We have stroked the trunk of healthy individuals while they watched the trunk of a virtual human that was facing them being synchronously stroked. Subjects sensed self-identification with the virtual body, which was accompanied by a decrease of their self-other face distinction. This suggests that face self-perception involves the self-other face distinction and that this mechanism is underlying the formation of a discrete representation of one's face. Moreover, the self-identification with another's body that we find suggests that the perception of one's full body affects the self-other face distinction. Hence, changes in self-other face distinction can indicate alterations of body self-perception, and thereby serve to elucidate the relationship of face and body self-perception. PMID- 26541058 TI - The Moon as a Tiny Bright Disc: Insights From Observations in the Planetarium. AB - Despite a relatively constant visual angle, the size of the moon appears very variable, mostly depending on elevation and context factors--the so-called moon illusion. As our perceptual experience of the size of the moon is clearly limited to the perceptual sphere of the sky, however, we do not know whether the typical perception of the moon at its zenith reflects a veridical interpretation of its visual angle of only 0.5 degrees. When testing the moon illusion in a large-scale planetarium, we observed two important things: (a) variation in perceptual size was no longer apparent, and (b) the moon looked very much smaller than in any viewing condition in the real sky--even when comparing it at its zenith. A closer inspection of the control console of the planetarium revealed that classic-analog as well as updated-digital planetariums use projections of the moon with strongly increased sizes to compensate for the loss of a natural view of the moon in the artificial dome of the sky. PMID- 26541059 TI - One-Pot Synthesis of N-(alpha-Peroxy)Indole/Carbazole via Chemoselective Three Component Condensation Reaction in Open Atmosphere. AB - A facile one-pot synthesis of N-(alpha-peroxy)indole and N-(alpha peroxy)carbazole has been developed using metal-free, organo-acid-catalyzed three component condensation reactions of indole/carbazole, aldehyde, and peroxide. Based on the reaction discovered, a new synthetic proposal for Fumitremorgin A and Verruculogen is introduced. Such a protocol could be easily handled and scaled up in an open atmosphere with a wide substrate scope, enabling the construction of a new molecule library. PMID- 26541060 TI - Prenatal vitamin D supplementation and infant vitamin D status in Bangladesh. AB - OBJECTIVE: To determine the effect of prenatal maternal vitamin D supplementation on infant vitamin D status in a tropical region where vitamin D supplementation is not routine. DESIGN: A prospective observational follow-up of a randomized trial. SETTING: Maternal-child health facility in Dhaka, Bangladesh (23 degrees N). SUBJECTS: Infants born to pregnant women (n 160) randomized to receive 875 ug (35 000 IU) cholecalciferol (vitamin D3) per week (VD) or placebo (PL) during the third trimester were followed from birth until 6 months of age (n 115). Infant serum 25-hydroxyvitamin D concentration (25(OH)D) was measured at <1, 2, 4 and 6 months of age. RESULTS: Mean infant 25(OH)D was higher in the VD v. PL group at <1 month of age (mean (sd): 80 (20) nmol/l v. 22 (18) nmol/l; P<0.001), but the difference was attenuated by 2 months (52 (19) nmol/l v. 40 (23) nmol/l; P=0.05). Groups were similar at 4 months (P=0.40) and 6 months (n 72; P=0.26). In the PL group, mean infant 25(OH)D increased to 78 (95 % CI 67, 88) nmol/l by 6 months of age (n 34). 25(OH)D was higher with infant formula-feeding and higher in summer v. winter. CONCLUSIONS: Prenatal third-trimester vitamin D supplementation (875 ug (35 000 IU)/week) significantly ameliorated infant vitamin D status during the neonatal period when the risk of vitamin D deficiency is greatest. Further research is warranted to determine factors that contribute to the rise in 25(OH)D during the first 6 months of life among breast-fed infants in this setting. PMID- 26541061 TI - The differentially methylated region of MEG8 is hypermethylated in patients with Temple syndrome. AB - AIM: To investigate the DNA-methylation levels in the newly described MEG8 differentially methylated region (DMR) in the imprinted cluster in 14q32 in patients with Temple syndrome. PATIENTS & METHODS: We included three patients with Temple syndrome which were studied by Infinium HumanMethylation450 BeadChips, locus-specific bisulfite-pyrosequencing, methylation-specific-MLPA and microsatellite analyses. The tag-CpG of the MEG8-DMR was investigated using the Infinium HumanMethylation450 BeadChip. RESULTS: In all three patients, the identical pattern of DNA-hypermethylation of the MEG8-DMR was observed along with DNA-hypomethylation of the IG-DMR and MEG3-DMR. CONCLUSION: Based on the observed MEG8-DMR DNA-hypermethylation and previously published data, we conclude that DNA methylation of the MEG3- and MEG8-DMR is functionally dependent on the DNA methylation pattern of the IG-DMR. The observed combination of epimutations is predicted to be associated with bi-allelic MEG3 and MEG8 expression in individuals with Temple syndrome. PMID- 26541062 TI - Real-time monitoring of fungal inhibition and morphological changes. AB - Mold growth constitutes a problem in many food and clinical environments and there is therefore focus on studying antifungal activity. Methods for determining growth inhibition by measuring colony growth or biomass are, however, time-taking and rapid methods for evaluation of antifungal effects are needed. Propionic acid and diacetyl are antifungal compounds produced by a range of dairy-associated bacteria. Their activity against Penicillium spp. was monitored real-time using an optical detection system with tilted focus plane to assess growth and morphological changes of Penicillium spp. by image recording inside a 96 well microplate. Images were used for generation of growth curves by using a segmentation and extraction of surface areas (SESA) algorithm and for quantifying morphology changes. Using image analysis growth could be detected within 15 h compared with more than 30 h when using standard optical density measurements. Induced morphological changes of fungi could furthermore be visualized and quantified using morphological descriptors such as circularity, branch points, perimeter and area of spores and growing hyphae. Propionic acid inhibited two out of two Penicillium spp. while morphological changes were strain dependent at the concentrations tested. Diacetyl inhibited six out of six Penicillium spp. strains and increased spore size and number of germination sites in two out of six of the strains prior to germination. PMID- 26541063 TI - Overexpression of quinone reductase from Salix matsudana Koidz enhances salt tolerance in transgenic Arabidopsis thaliana. AB - Quinone reductase (QR) is an oxidative-related gene and few studies have focused on its roles concerning salt stress tolerance in plants. In this study, we cloned and analyzed the QR gene from Salix matsudana, a willow with tolerance of moderate salinity. The 612-bp cDNA corresponding to SmQR encodes 203 amino acids. Expression of SmQR in Escherichia coli cells enhanced their tolerance under salt stress. In addition, transgenic Arabidopsis thaliana lines overexpressing SmQR exhibited higher salt tolerance as compared with WT, with higher QR activity and antioxidant enzyme activity as well as higher chlorophyll content, lower methane dicarboxylic aldehyde (MDA) content and electric conductivity under salt stress. Nitro blue tetrazolium (NBT) and 3,3'-diaminobenzidine (DAB) staining also indicated that the transgenic plants accumulated less reactive oxygen species compared to WT when exposed to salt stress. Overall, our results suggested that SmQR plays a significant role in salt tolerance and that this gene may be useful for biotechnological development of plants with improved tolerance of salinity. PMID- 26541064 TI - Increasing prevalence of thalassemia in America: Implications for primary care. AB - Thalassemia, once a rarity in the United States, is increasingly encountered in clinical practice due to shifts in immigration. Early carrier screening in at risk populations can help clinicians implement genetic counseling and prevent new cases. Chronic transfusions are the mainstay of therapy for patients with severe thalassemia (beta thalassemia major), and are used intermittently in individuals with milder forms of thalassemia (Hb H/H Constant Spring disease and beta thalassemia intermedia). Iron overload is a major source of morbidity and mortality in individuals with transfusion and non-transfusion-dependent thalassemia, necessitating iron chelation therapy. Iron overload contributes to increased risk of cirrhosis, heart failure, and endocrinopathies, while ineffective erythropoiesis and hemolysis contribute to multiple complications, including splenomegaly, extramedullary hematopoiesis, pulmonary hypertension, and thrombosis. An understanding of the importance of carrier screening, complications, monitoring, and management strategies, coupled with collaboration with a hematologist with thalassemia expertise, is essential to reduce the morbidity and mortality in patients with thalassemia. PMID- 26541065 TI - [Ectoparasitic diseases: A good example of the concept "one world one health"]. PMID- 26541066 TI - Direct Measurement of Water States in Cryopreserved Cells Reveals Tolerance toward Ice Crystallization. AB - Complex living systems such as mammalian cells can be arrested in a solid phase by ultrarapid cooling. This allows for precise observation of cellular structures as well as cryopreservation of cells. The state of water, the main constituent of biological samples, is crucial for the success of cryogenic applications. Water exhibits many different solid states. If it is cooled extremely rapidly, liquid water turns into amorphous ice, also called vitreous water, a glassy and amorphous solid. For cryo-preservation, the vitrification of cells is believed to be mandatory for cell survival after freezing. Intracellular ice crystallization is assumed to be lethal, but experimental data on the state of water during cryopreservation are lacking. To better understand the water conditions in cells subjected to freezing protocols, we chose to directly analyze their subcellular water states by cryo-electron microscopy and tomography, cryoelectron diffraction, and x-ray diffraction both in the cryofixed state and after warming to different temperatures. By correlating the survival rates of cells with their respective water states during cryopreservation, we found that survival is less dependent on ice-crystal formation than expected. Using high-resolution cryo imaging, we were able to directly show that cells tolerate crystallization of extra- and intracellular water. However, if warming is too slow, many small ice crystals will recrystallize into fewer but bigger crystals, which is lethal. The applied cryoprotective agents determine which crystal size is tolerable. This suggests that cryoprotectants can act by inhibiting crystallization or recrystallization, but they also increase the tolerance toward ice-crystal growth. PMID- 26541067 TI - Retrospective cohort study evaluating the incidence of diabetic foot infections among hospitalized adults with diabetes in the United States from 1996-2010. AB - BACKGROUND: The prevalence of diabetes has increased over the last 2 decades; however, the national incidence of diabetic foot infections (DFIs) in the United States is unknown. We sought to determine national trends in DFIs among hospitalized adults in the United States over 15 years. METHODS: This was a retrospective cohort study of the U.S. National Hospital Discharge Survey from 1996-2010. Adult patients with a principal diagnosis of foot infection and a secondary diagnosis of diabetes were identified using ICD-9-CM codes. Incidence was defined as DFI discharges per 100 diabetes discharges. Independent risk factors for DFI among diabetics were identified using multivariable logistic regression. RESULTS: These data represent 1,059,552 DFI discharges over the study period. The incidence of DFI decreased from 1996 (2.3 DFIs/100 diabetes discharges) to 2010 (1.1 DFI/100 diabetes discharges). The proportion of patients experiencing lower-extremity amputation declined from 33.2% in 1996 to 17.1% in 2010. Peripheral vascular disease (odds ratio [OR], 2.89; 95% confidence interval [CI], 2.87-2.91), peripheral neuropathy (OR, 2.62; 95% CI, 2.60-2.64), and male sex (OR, 1.67; 95% CI, 1.66-1.68) were the leading risk factors for DFI. CONCLUSION: The incidence of DFI among hospitalized adults in the United States declined by more than half from 1996-2010. PMID- 26541068 TI - Multidisciplinary performance improvement team for reducing health care associated Clostridium difficile infection. AB - Clostridium difficile is the most frequent cause of health care-associated diarrhea and is a significant cause of morbidity and mortality. It is also associated with a considerable financial burden. A concerted multidisciplinary approach is required for prevention. PMID- 26541069 TI - Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling. AB - In this study, we investigated potentially probiotic Bacillus licheniformis strains isolated from traditional Korean food sources for ability to enhance longevity using the nematode Caenorhabditis elegans as a simple in vivo animal model. We first investigated whether B. licheniformis strains were capable of modulating the lifespan of C. elegans. Among the tested strains, preconditioning with four B. licheniformis strains significantly enhanced the longevity of C. elegans. Unexpectedly, plate counting and transmission electron microscopy (TEM) results indicated that B. licheniformis strains were not more highly attached to the C. elegans intestine compared with Escherichia coli OP50 or Lactobacillus rhamnosus GG controls. In addition, qRT-PCR and an aging assay with mutant worms showed that the conditioning of B. licheniformis strain 141 directly influenced genes associated with serotonin signaling in nematodes, including tph-1 (tryptophan hydroxylase), bas-1 (serotonin- and dopamine-synthetic aromatic amino acid decarboxylase), mod-1 (serotonin-gated chloride channel), ser-1, and ser-7 (serotonin receptors) during C. elegans aging. Our findings suggest that B. licheniformis strain 141, which is isolated from traditional Korean foods, is a probiotic generally recognized as safe (GRAS) strain that enhances the lifespan of C. elegans via host serotonin signaling. PMID- 26541070 TI - Adjunct High Frequency Transcutaneous Electric Stimulation (TENS) for Postoperative Pain Management during Weaning from Epidural Analgesia Following Colon Surgery: Results from a Controlled Pilot Study. AB - The potential benefit of nonpharmacological adjunctive therapy is not well studied following major abdominal surgery. The aim of the present study was to investigate transcutaneous electrical nerve stimulation (TENS) as a complementary nonpharmacological analgesia intervention during weaning from epidural analgesia (EDA) after open lower abdominal surgery. Patients were randomized to TENS and sham TENS during weaning from EDA. The effects on pain at rest, following short walk, and after deep breath were assessed by visual analog scale (VAS) grading. Number of patients assessed was lower than calculated because of change in clinical routine. Pain scores overall were low. A trend of lower pain scores was observed in the active TENS group of patients; a statistical significance between the groups was found for the pain lying prone in bed (p < .05). This controlled pilot study indicates benefits of TENS use in postoperative pain management during weaning from EDA after open colon surgery. Further studies are warranted in order to verify the potential beneficial effects from TENS during weaning from EDA after open, lower abdominal surgery. PMID- 26541071 TI - Computation of the effective mechanical response of biological networks accounting for large configuration changes. AB - The asymptotic homogenization technique is involved to derive the effective elastic response of biological membranes viewed as repetitive beam networks. Thereby, a systematic methodology is established, allowing the prediction of the overall mechanical properties of biological membranes in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the equivalent continuum. Biomembranes networks are classified based on nodal connectivity, so that we analyze in this work 3, 4 and 6-connectivity networks, which are representative of most biological networks. The individual filaments of the network are described as undulated beams prone to entropic elasticity, with tensile moduli determined from their persistence length. The effective micropolar continuum evaluated as a continuum substitute of the biological network has a kinematics reflecting the discrete network deformation modes, involving a nodal displacement and a microrotation. The statics involves the classical Cauchy stress and internal moments encapsulated into couple stresses, which develop internal work in duality to microcurvatures reflecting local network undulations. The relative ratio of the characteristic bending length of the effective micropolar continuum to the unit cell size determines the relevant choice of the equivalent medium. In most cases, the Cauchy continuum is sufficient to model biomembranes. The peptidoglycan network may exhibit a re-entrant hexagonal configuration due to thermal or pressure fluctuations, for which micropolar effects become important. The homogenized responses are in good agreement with FE simulations performed over the whole network. The predictive nature of the employed homogenization technique allows the identification of a strain energy density of a hyperelastic model, for the purpose of performing structural calculations of the shape evolutions of biomembranes. PMID- 26541072 TI - Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer. AB - OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC. PMID- 26541073 TI - Molecular Breeding for Improved Second Generation Bioenergy Crops. AB - There is increasing urgency to develop and deploy sustainable sources of energy to reduce our global dependency on finite, high-carbon fossil fuels. Lignocellulosic feedstocks, used in power and liquid fuel generation, are valuable sources of non-food plant biomass. They are cultivated with minimal inputs on marginal or degraded lands to prevent competition with arable agriculture and offer significant potential for sustainable intensification (the improvement of yield without the necessity for additional inputs) through advanced molecular breeding. This article explores progress made in next generation sequencing, advanced genotyping, association genetics, and genetic modification in second generation bioenergy production. Using poplar as an exemplar where most progress has been made, a suite of target traits is also identified giving insight into possible routes for crop improvement and deployment in the immediate future. PMID- 26541074 TI - Are there specific translational challenges in regenerative medicine? Lessons from other fields. AB - There is concern that translation 'from bench to bedside' within regenerative medicine (RM) will fail to materialize, or will be dismally slow, due to various challenges arising from the highly novel and disruptive nature of RM. In this article, we provide a summary of these challenges, and we critically engage with the notion that such challenges are specific to RM. It is important, we argue, not to overstate the exceptional nature of RM, as valuable lessons can be learned from elsewhere in medicine. Using several examples of technology adoption, we suggest that emerging RM products and procedures will have to work hard to find or create an adoption space if translation into the clinic is to be successful. PMID- 26541075 TI - Impact of postprandial glucose control on diabetes-related complications: How is the evidence evolving? AB - Conflicting findings in the literature and lack of long-term definitive outcome studies have led to difficulty in drawing conclusions about the role of postprandial hyperglycemia in diabetes and its complications. Recent scientific publications support the role of postprandial glucose (PPG) as a key contributor to overall glucose control and a predictor of microvascular and macrovascular events. However, the need remains for definitive evidence to support the precise relationship between PPG excursions and the development and progression of cardiovascular complications of diabetes. Drawing firm conclusions on the relationship between PPG and microvascular and macrovascular complications is challenged by the absence of antidiabetic agents that can specifically exert their action on PPG alone, without a basal glucose-lowering effect. Areas under investigation include interventions that more closely approximate 'normal' physiological postprandial responses, as well as technologies that advance the mode of insulin delivery or optimize methods to sense glycemic levels and variation. In conclusion, the precise role of postprandial hyperglycemia in relation to development of diabetic complications is unclarified and is one of the remaining unanswered questions in diabetes. Nevertheless, current evidence supports PPG control as an important strategy to consider in the comprehensive management plan of individuals with diabetes. PMID- 26541076 TI - The EMPA-REG study: What has it told us? A diabetologist's perspective. PMID- 26541077 TI - Do Patients Treated for Colorectal Cancer Benefit from General Practitioner Support? A Video Vignette Study. AB - BACKGROUND: Patients who have been treated for colorectal cancer in Australia can consult their general practitioner (GP) for advice about symptoms or side effects at any time following their treatment. However, there is no evidence that such patients are consistently advised by GPs, and patients experience substantial unmet need for reassurance and advice. OBJECTIVE: To explore the patient management options selected by GPs to treat a set of patients describing their symptoms following treatment for colorectal cancer. METHODS: This was an Internet based survey. Participants (GPs) viewed 6 video vignettes of actors representing patients who had been treated for colorectal cancer. The actor-patients presented problems that resulted from their treatment. Participants indicated their diagnosis and stated if they would prescribe, refer, or order tests, based on that diagnosis. These responses were then rated against the management decisions for those vignettes as recommended by a team of colorectal cancer experts. RESULTS: In total, 52 GPs consented to take part in the study, and 40 (77%) completed the study. Most GPs made a diagnosis of colorectal cancer treatment side effects/symptoms of recurrence that was consistent with the experts' opinions. However, correct diagnosis was dependent on the type of case viewed. Compared with radiation proctitis, GPs were more likely to recognize peripheral neuropathy (odds ratio, OR, 4.43, 95% CI 1.41-13.96, P=.011) and erectile dysfunction (OR 9.70, 95% CI 2.48-38.03, P=.001), but less likely to identify chemotherapy-induced fatigue (OR 0.19, 95% CI 0.08-0.44). GPs who had more hours of direct patient care (OR 0.38, 95% CI 0.17-0.84, P=.02), were experienced (OR 9.78, 95% CI 1.18-8.84, P=.02), and consulted more patients per week (OR 2.48, 95% CI 1.16-5.30, P=.02) suggested a management plan that was consistent with the expert opinion. CONCLUSIONS: In this pilot study, years of experience and direct patient contact hours had a significant and positive impact on the management of patients. This study also showed promising results indicating that management of the common side effects of colorectal cancer treatment can be delegated to general practice. Such an intervention could support the application of shared models of care. However, a larger study, including the management of side effects in real patients, needs to be conducted before this can be safely recommended. PMID- 26541078 TI - Biophysical and biological characterisation of collagen/resilin-like protein composite fibres. AB - Collagen type I, in various physical forms, is widely used in tissue engineering and regenerative medicine. To control the mechanical properties and biodegradability of collagen-based devices, exogenous cross-links are introduced into the 3D supramolecular structure. However, potent cross-linking methods are associated with cytotoxicity, whilst mild cross-linking methods are associated with suboptimal mechanical resilience. Herein, we assessed the influence of resilin, a super-elastic and highly stretchable protein found within structures in arthropods where energy storage and long-range elasticity are needed, on the biophysical and biological properties of mildly cross-linked extruded collagen fibres. The addition of resilin-like protein in the 4-arm poly(ethylene glycol) ether tetrasuccinimidyl glutarate cross-linked collagen fibres resulted in a significant increase of stress and strain at break values and a significant decrease of modulus values. The addition of resilin-like protein did not compromise cell metabolic activity and DNA concentration. All groups are supported parallel to the longitudinal fibre axis cell orientation. Herein we provide evidence that the addition of resilin-like protein in mildly cross-linked collagen fibres improves their biomechanical properties, without jeopardising their biological properties. PMID- 26541080 TI - Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma. AB - PURPOSE: Margin status can often be difficult to assess intraoperatively, particularly during partial nephrectomy given the time constraints related to renal hilar clamping. We hypothesized that a targeted molecular imaging approach could be used during surgery to identify tumor margins and confirm disease clearance. MATERIALS AND METHODS: EC17, a novel tracer targeting FRalpha, was used in murine models of renal cell carcinoma to identify positive margins after surgery. Positive margins were detected due to elevated tumor-to-background ratios of the tumor compared to surrounding normal tissues. We performed a pilot study in 4 patients using EC17 preoperatively with intraoperative imaging during the operation. RESULTS: FRalpha was highly expressed in 65% of clear cell renal cell carcinomas harvested from the operating room. In the murine model intraoperative imaging of renal cell carcinoma revealed a mean +/- SD tumor-to background ratio of 8.2 +/- 1.1 in the RCC10, 11.2 +/- 1.1 in the 786-0 and 4.3 +/- 1.1 in the UMRC2 cell line. Compared to visual inspection intraoperative imaging of the surgical resection bed identified residual disease in 24% more animals. In the human pilot study targeted molecular imaging identified 2 of 4 renal cell carcinomas and had no false-positive results. In these 2 cases the tumor-to-background ratio was 3.7 and 4.6, respectively. In each case we confirmed disease clearance and tumor fluorescence did not correlate with nodule size or tumor grade. CONCLUSIONS: To our knowledge this is the first demonstration in humans of identifying renal cell carcinoma during surgery using a targeted molecular contrast agent. This approach may lead to a superior method of identifying malignancy and tumor borders in the intraoperative setting. PMID- 26541082 TI - Feature diagnosticity and task context shape activity in human scene-selective cortex. AB - Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer. PMID- 26541083 TI - Bipolar Carrier Transfer Channels in Epitaxial Graphene/SiC Core-Shell Heterojunction for Efficient Photocatalytic Hydrogen Evolution. AB - Bipolar carrier transfer channels exist in the in situ epitaxial-graphene-wrapped 6H-SiC core-shell heterojunction due to the self-doping of graphene. Due to the special interface structure and high graphene quality, this material exhibits significant photocatalytic enhancement. Its hydrogen evolution efficiency is greater than that of the Pt/SiC composite. This micrometer-sized metal-free photocatalyst exhibits an activity comparable to that of metal-based nanophotocatalysts. PMID- 26541084 TI - The emerging epitranscriptomics of long noncoding RNAs. AB - The pervasive transcription of genomes into long noncoding RNAs has been amply demonstrated in recent years and garnered much attention. Similarly, emerging 'epitranscriptomics' research has shown that chemically modified nucleosides, thought to be largely the domain of tRNAs and other infrastructural RNAs, are far more widespread and can exert unexpected influence on RNA utilization. Both areas are characterized by the often-ephemeral nature of the subject matter in that few individual examples have been fully assessed for their molecular or cellular function, and effects might often be subtle and cumulative. Here we review available information at the intersection of these two exciting areas of biology, by focusing on four RNA modifications that have been mapped transcriptome-wide: 5 methylcytidine, N6-methyladenosine, pseudouridine as well as adenosine to inosine (A-to-I) editing, and their incidence and function in long noncoding RNAs. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26541086 TI - Comparison of subfoveal choroidal thickness in healthy pregnancy and pre eclampsia. AB - PURPOSE: Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women.Patients and methodsThis was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. RESULTS: The mean CT of normal subjects, healthy pregnant women and patients with pre eclampsia were 264.95+/-21.03, 274.23+/-29.30 and 389.79+/-25.13 MUm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05+/-22.96 MUm to 335.17+/-9.97 MUm 1 week after delivery in patients with pre-eclampsia. CONCLUSIONS: Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women. PMID- 26541085 TI - Light pollution: the possible consequences of excessive illumination on retina. AB - Light is the visible part of the electromagnetic radiation within a range of 380 780 nm; (400-700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution. PMID- 26541087 TI - Light and the evolution of vision. AB - It might seem a little ridiculous to cover the period over which vision evolved, perhaps 1.5 billion years, in only 3000 words. Yet, if we examine the photoreceptor molecules of the most basic eukaryote protists and even before that, in those of prokaryote bacteria and cyanobacteria, we see how similar they are to those of mammalian rod and cone photoreceptor opsins and the photoreceptive molecules of light sensitive ganglion cells. This shows us much with regard the development of vision once these proteins existed, but there is much more to discover about the evolution of even more primitive vision systems. PMID- 26541088 TI - Light damage to the retina: an historical approach. AB - A brief review of retinal light damage is presented. Thermal damage requires a local rise in temperature of at least 10 degrees C, causing an instant denaturation of proteins. The primary absorber is melanin. Photochemical damage occurs at body temperature and involves cellular damage by reactive forms of oxygen. The photosensitizers are photoproducts of the visual pigments. First indications that non-thermal damage might exist, in particular in the case of eclipse blindness, was presented by Vos in 1962. Attribution thereof to photochemical action was presented in 1966 by Noell et al who also measured the first action spectrum, in rat. It turned out to be identical to the absorption spectrum of rhodopsin. However, in 1976 and 1982 Ham et al found a quite different spectrum in monkeys, peaking at short wavelengths. The latter spectrum, but not the former, was confirmed since in numerous publications with animal models including rat. In ophthalmological practice a 'sunburn' was at first the only complaint caused by light damage. To avoid this, patients with dilated pupils should always be advised to wear sunglasses. Since the invention of the laser accidents have been reported, the most recent development is youth playfully pointing a strong laser pen in their eyes with marked consequences. The operation microscope and endoilluminators should always be used as brief as possible to avoid photochemical damage. Arguments for implant lenses that block not only the UV but also part of the visible spectrum seem too weak to justify extra costs. PMID- 26541089 TI - The influence of hydrogeological disturbance and mining on coal seam microbial communities. AB - The microbial communities present in two underground coal mines in the Bowen Basin, Queensland, Australia, were investigated to deduce the effect of pumping and mining on subsurface methanogens and methanotrophs. The micro-organisms in pumped water from the actively mined areas, as well as, pre- and post-mining formation waters were analyzed using 16S rRNA gene amplicon sequencing. The methane stable isotope composition of Bowen Basin coal seam indicates that methanogenesis has occurred in the geological past. More recently at the mine site, changing groundwater flow dynamics and the introduction of oxygen in the subsurface has increased microbial biomass and diversity. Consistent with microbial communities found in other coal seam environments, pumped coal mine waters from the subsurface were dominated by bacteria belonging to the genera Pseudomonas and the family Rhodocyclaceae. These environments and bacterial communities supported a methanogen population, including Methanobacteriaceae, Methanococcaceae and Methanosaeta. However, one of the most ubiquitous micro organisms in anoxic coal mine waters belonged to the family 'Candidatus Methanoperedenaceae'. As the Archaeal family 'Candidatus Methanoperedenaceae' has not been extensively defined, the one studied species in the family is capable of anaerobic methane oxidation coupled to nitrate reduction. This introduces the possibility that a methane cycle between archaeal methanogenesis and methanotrophy may exist in the anoxic waters of the coal seam after hydrogeological disturbance. PMID- 26541090 TI - Fine-tuning of synaptic upscaling at excitatory synapses by endocannabinoid signaling is mediated via the CB1 receptor. AB - The endocannabinoid 2-arachidonoylglycerol (2-AG) functions as a retrograde signaling molecule mediating synaptic transmission and plasticity at both inhibitory and excitatory synapses. However, little is known about whether 2-AG signaling is involved in homeostatic regulation of miniature synaptic events at excitatory synapses in response to activity deprivation. Here, we report that chronic blockade of firing by tetrodotoxin (TTX) for two days resulted in increases both in the frequency and amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in cultured mouse hippocampal neurons. However, treatment with 2-AG alone or JZL184, a potent and selective inhibitor for monoacylglycerol lipase (MAGL) that hydrolyzes 2-AG, induced a CB1 receptor dependent reduction of the frequency of mEPSCs, but not the amplitude. The TTX increased frequency was blunted by 2-AG or JZL184 and this effect was eliminated by pharmacological or genetic inhibition of CB1 receptors. In addition, TTX still increased frequency and amplitude of mEPSCs in the presence of CB1 receptor inhibition. Our results suggest that while endocannabinoids are not required for induction of synaptic scaling at excitatory glutamate synapses after chronic activity deprivation, 2-AG signaling may play a role in fine-tuning of synaptic strengths via presynaptically-expressed CB1 receptors. PMID- 26541091 TI - Determinants of long-term quality of life in patients with differentiated thyroid carcinoma - a population-based cohort study in Sweden. AB - BACKGROUND: Although differentiated thyroid cancer (DTC) has an excellent prognosis and a low incidence of recurrence, lifelong follow-up and medication might be needed. The aim of this study was to clarify how living with a cancer diagnosis for many years affects health-related quality of life (HRQoL) in DTC patients in Sweden. MATERIAL AND METHODS: From the national all-encompassing population-based Swedish Cancer Registry, 353 patients diagnosed with DTC between 1995 and 1998 were identified and invited to answer the HRQoL questionnaire SF-36 and a study-specific questionnaire, 14-17 years after their diagnosis. Data were compared with a reference population as well between subgroups of patients. RESULTS: Of the patients with DTC, 279 (79%) answered the questionnaires. In all, only 19 (7%) reported a recurrence, however, as many as 134 (48%) stated that they still had concerns about having a recurrence. The HRQoL in those with a recurrence was significantly lower than those without concerns of a recurrence in five of eight domains (p < 0.001-0.049). Similarly, patients with concerns of a recurrence reported poorer HRQoL than those without concerns, with significantly lower values in five domains (p < 0.001-0.008). Those few who stated that their disease had given them a negative view on life reported poor HRQoL in all eight domains (p < 0.001-0.030). CONCLUSIONS: Even if DTC comes with an excellent prognosis, almost half of the patients, fully 15 years after diagnosis, worried about a recurrence which negatively impacted their HRQoL. Awareness among healthcare practitioners might improve information, supportive care and, in the end, the patient's HRQoL. PMID- 26541092 TI - Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Baseline and Peri-Operative Care Data Elements. AB - Chronic subdural hematoma (CSDH) is an increasingly common subtype of head injury, especially in the elderly population. The optimization of treatment strategies has been hampered by the collection of heterogeneous outcome measures and data elements, precluding cross-study comparisons. This study aimed to quantify the heterogeneity of data elements in the pre-operative, operative, and post-operative phases of care, and build the basis for the development of a set of common data elements (CDEs) for CSDH. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO register of systematic reviews (CRD42014007266). All full-text English studies with more than 10 patients (prospective) or more than 100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. Only 40 studies (39.2%) reported the main presenting symptom/feature and 24 (23.5%) reported additional symptoms/features. Admitting neurological/functional status was classified by the Glasgow Coma Scale (25 studies; 24.5%), the Markwalder Score (26 studies; 25.5%) and the modified Rankin Scale (three studies; 2.9%). Fifty-four studies (52.9%) made some mention of patient comorbidities and 58 studies (56.9%) reported the proportion or excluded patients on anticoagulant medication. Eighteen studies (17.6%) reported baseline coagulation status. Sixty-four studies (62.7%) stratified or assessed severity based on radiological findings, although the methods used varied widely. There was variable reporting of surgical technique and post-operative care; 32 studies (31.4%) made no mention of whether the operations were performed under general or local anesthetic. This study, a part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project, confirms and quantifies the heterogeneity of data elements collected and reported in CSDH studies to date. It establishes the basis for the consensus-based development of a set of common data elements, facilitating robust cross-study comparisons and resulting improvements in patient outcomes. PMID- 26541093 TI - Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women. AB - BACKGROUND: We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. METHODS: 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. RESULTS: At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. CONCLUSION: Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. PMID- 26541095 TI - Reversible single-crystal-to-single-crystal transformation from a mononuclear complex to a fourfold interpenetrated MOF with selective adsorption of CO2. AB - The reversible crystal transformation between the mononuclear complex [Cu(tzbc)2(H2O)4] (1) and the 4-fold interpenetrated diamondoid MOF [Cu(tzbc)2] (2) was chemically implemented and structurally interpreted. Interestingly, despite 4-fold interpenetration, desolvated with 1D channels and rich N-groups shows exclusive CO2 adsorption of up to 12.5 wt% at room temperature and low pressure, indicating potential application in the separation of industrial and automobile exhaust. PMID- 26541094 TI - Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions. AB - Myocardial perfusion and coronary vascular resistance are regulated by signaling metabolites released from the local myocardium that act either directly on the VSMC or indirectly via stimulation of the endothelium. A prominent mechanism of vasodilation is EDH of the arteriolar smooth muscle, with EETs and H(2)O(2) playing important roles in EDH in the coronary microcirculation. In some cases, EETs and H(2)O(2) are released as transferable hyperpolarizing factors (EDHFs) that act directly on the VSMCs. By contrast, EETs and H(2)O(2) can also promote endothelial KCa activity secondary to the amplification of extracellular Ca(2+) influx and Ca(2+) mobilization from intracellular stores, respectively. The resulting endothelial hyperpolarization may subsequently conduct to the media via myoendothelial gap junctions or potentially lead to the release of a chemically distinct factor(s). Furthermore, in human isolated coronary arterioles dilator signaling involving EETs and H(2)O(2) may be integrated, being either complimentary or inhibitory depending on the stimulus. With an emphasis on the human coronary microcirculation, this review addresses the diverse and integrated mechanisms by which EETs and H(2)O(2) regulate vessel tone and also examines the hypothesis that myoendothelial microdomain signaling facilitates EDH activity in the human heart. PMID- 26541097 TI - High genetic variability in endophytic fungi from the genus Diaporthe isolated from common bean (Phaseolus vulgaris L.) in Brazil. AB - AIMS: The goals of the present study were to identify, to analyse the phylogenetic relations and to evaluate the genetic variability in Diaporthe endophytic isolates from common bean. METHODS AND RESULTS: Diaporthe sp., D. infecunda and D. phaseolorum strains were identified using multilocus phylogeny (rDNA ITS region; EF1-alpha, beta-tubulin, and calmodulin genes). IRAP (Inter Retrotransposon Amplified Polymorphism) and REMAP (Retrotransposon-Microsatellite Amplified Polymorphism) molecular markers reveal the existence of high genetic variability, especially among D. infecunda isolates. CONCLUSIONS: It was concluded that the multilocus phylogenetic approach was more effective than individual analysis of ITS sequences, in identifying the isolates to species level, and that IRAP and REMAP markers can be used for studying the genetic variability in the genus Diaporthe particularly at the intraspecific level. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined use of molecular tools such as multilocus phylogenetic approach and molecular markers, as performed in this study, is the best way to distinguish endophytic strains of Diaporthe isolated from common bean (Phaseolus vulgaris L.). PMID- 26541096 TI - The effect of short-chain fatty acids on human monocyte-derived dendritic cells. AB - The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS) induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID- 26541098 TI - A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer. AB - CONTEXT: Ovarian cancer is common and has significant morbidity and mortality, partly because it is often diagnosed at a late stage. This study sought to determine the accuracy of individual symptoms and combinations of symptoms for the diagnosis of ovarian cancer. EVIDENCE ACQUISITION: MEDLINE was searched, identifying 2,492 abstracts, reviewing 71 articles in full, and ultimately identifying 17 studies published between 2001 and 2014 that met the inclusion criteria. Data were abstracted by two researchers, and quality was assessed using the QUADAS-2 criteria adapted to the study question. Bivariate random effects meta-analysis was used where possible, and heterogeneity and threshold effects were explored using receiver operating characteristic curves. Data were analyzed in 2015. EVIDENCE SYNTHESIS: Most studies were at high risk of bias, primarily because of case-control design or differential verification bias. The highest positive likelihood ratios (LRs+) were found for presence of abdominal mass (LR+, 30.0); abdominal distension or increased girth (LR+, 16.0); abdominal or pelvic pain (LR+, 10.4); abdominal or pelvic bloating (LR+, 9.3); loss of appetite (LR+, 9.2); and a family history of ovarian cancer (LR+, 7.5). No symptoms were helpful at ruling out ovarian cancer when absent. The Ovarian Cancer Symptom Index was validated in five studies and (after excluding one outlier with different inclusion criteria) was 63% sensitive and 95% specific (LR+, 12.6; LR-, 0.39). Two other symptom scores had not been validated prospectively. CONCLUSIONS: Several individual signs and symptoms significantly increase the likelihood of ovarian cancer when present. More work is needed to validate decision rules and develop new decision support tools integrating risk factors, symptoms, and possibly biomarkers to identify women at increased ovarian cancer risk. PMID- 26541099 TI - Multi-College Bystander Intervention Evaluation for Violence Prevention. AB - INTRODUCTION: The 2013 Campus Sexual Violence Elimination Act requires U.S. colleges to provide bystander-based training to reduce sexual violence, but little is known about the efficacy of such programs for preventing violent behavior. This study provides the first multiyear evaluation of a bystander intervention's campus-level impact on reducing interpersonal violence victimization and perpetration behavior on college campuses. METHODS: First-year students attending three similarly sized public university campuses were randomly selected and invited to complete online surveys in the spring terms of 2010-2013. On one campus, the Green Dot bystander intervention was implemented in 2008 (Intervention, n=2,979) and two comparison campuses had no bystander programming at baseline (Comparison, n=4,132). Data analyses conducted in 2014-2015 compared violence rates by condition over the four survey periods. Multivariable logistic regression was used to estimate violence risk on Intervention relative to Comparison campuses, adjusting for demographic factors and time (2010-2013). RESULTS: Interpersonal violence victimization rates (measured in the past academic year) were 17% lower among students attending the Intervention (46.4%) relative to Comparison (55.7%) campuses (adjusted rate ratio=0.83; 95% CI=0.79, 0.88); a similar pattern held for interpersonal violence perpetration (25.5% in Intervention; 32.2% in Comparison; adjusted rate ratio=0.79; 95% CI=0.71, 0.86). Violence rates were lower on Intervention versus Comparison campuses for unwanted sexual victimization, sexual harassment, stalking, and psychological dating violence victimization and perpetration (p<0.01). CONCLUSIONS: Green Dot may be an efficacious intervention to reduce violence at the community level and meet Campus Sexual Violence Elimination Act bystander training requirements. PMID- 26541101 TI - Determination of hexavalent chromium in traditional Chinese medicines by high performance liquid chromatography with inductively coupled plasma mass spectrometry. AB - An analytical method that combined high-performance liquid chromatography with inductively coupled plasma mass spectrometry has been developed for the determination of hexavalent chromium in traditional Chinese medicines. Hexavalent chromium was extracted using the alkaline solution. The parameters such as the concentration of alkaline and the extraction temperature have been optimized to minimize the interconversion between trivalent chromium and hexavalent chromium. The extracted hexavalent chromium was separated on a weak anion exchange column in isocratic mode, followed by inductively coupled plasma mass spectrometry determination. To obtain a better chromatographic resolution and sensitivity, 75 mM NH4 NO3 at pH 7 was selected as the mobile phase. The linearity of the proposed method was investigated in the range of 0.2-5.0 MUg L(-1) (r(2) = 0.9999) for hexavalent chromium. The limits of detection and quantitation are 0.1 and 0.3 MUg L(-1) , respectively. The developed method was successfully applied to the determination of hexavalent chromium in Chloriti lapis and Lumbricus with satisfactory recoveries of 95.8-112.8%. PMID- 26541102 TI - Intramolecular C?H Activation and Metallacycle Aromaticity in the Photochemistry of [FeFe]-Hydrogenase Model Compounds in Low-Temperature Frozen Matrices. AB - The [FeFe]-hydrogenase model complexes [(MU-pdt){Fe(CO)3 }2 ], [(MU-edt){Fe(CO)3 }2 ], and [(MU-mdt){Fe(CO)3 }2 ], where pdt=1,3-propanedithiolate, edt=1,2 ethanedithiolate, and mdt=methanedithiolate, undergo wavelength dependent photodecarbonylation in hydrocarbon matrices at 85 K resulting in multiple decarbonylation isomers. As previously reported in time-resolved solution photolysis experiments, the major photoproduct is attributed to a basal carbonyl loss species. Apical carbonyl-loss isomers are also generated and may undergo secondary photolysis, resulting in beta-hydride activation of the alkyldithiolate bridge, as well as formation of bridging carbonyl isomers. For [(MU-bdt){Fe(CO)3 }2 ], (bdt=1,2-benzenedithiolate), apical photodecarbonylation results in generation of a 10 pi-electron aromatic FeS2 C6 H4 metallacycle that coordinates the remaining iron through an eta(5) mode. PMID- 26541100 TI - Modeling and measurement of vesicle pools at the cone ribbon synapse: Changes in release probability are solely responsible for voltage-dependent changes in release. AB - Postsynaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca(2+) entry alter postsynaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial postsynaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca(2+) spread by lowering Ca(2+) buffering or applying BayK8644 did not increase PSCs evoked with strong test steps, showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability. PMID- 26541103 TI - Big-bubble deep anterior lamellar keratoplasty using central vs peripheral air injection: a clinical trial. AB - PURPOSE: To compare 2 sites of air injection to achieve Descemet membrane (DM) detachment in big-bubble deep anterior lamellar keratoplasty (DALK). METHODS: In this prospective, randomized study, 48 eyes of 48 keratoconus-affected patients who underwent DALK by cornea fellows were enrolled. Each patient was randomly assigned into one of 2 groups. After trephination to approximately 80% of the corneal thickness, a 27-G needle was inserted into the stroma from the trephination site. The needle was moved radially inside the trephination site and advanced to the central or paracentral cornea in group 1. In group 2, the needle was inserted into the deep stroma from the trephination site and advanced into the peripheral cornea to approximately 1.5 mm anterior to the limbus. Air was gently injected into the deep stroma until a big bubble was formed. The rates of DM separation and complications were compared between the 2 groups. RESULTS: Big bubble formation was successful in 79.2% of the eyes in the study group. A bare DM was achieved by central injection in 68.0% of group 1 and by peripheral injection in 69.6% of group 2 (p = 0.68). This rate was increased to 80.0% and 78.3% in groups 1 and 2, respectively, after the injection site was shifted when injections failed. The study groups were comparable in terms of complications including DM perforation and bubble bursting. CONCLUSIONS: Both injection sites were equivalent in their rates of big-bubble formation and complications. Less experienced surgeons are advised to initially inject air outside the trephination. PMID- 26541104 TI - Anterior corneal surface irregularity after Descemet-stripping endothelial keratoplasty for bullous keratopathy. AB - PURPOSE: To evaluate irregularity of the anterior cornea before and after Descemet stripping endothelial keratoplasty (DSEK) for bullous keratopathy and its effect on visual acuity. METHODS: Corneal data were acquired using a topographic unit before and up to 12 months after DSEK. Anterior corneal elevation data were decomposed into a set of Zernike polynomials up to the 8th order within a 6.0-mm diameter region. Total higher-order aberrations (HOAs) and root mean square from the 3rd to 8th order were calculated. The effects of anterior surface irregularity on visual acuity were evaluated. RESULTS: This clinical study comprised 20 consecutive eyes of 20 patients with bullous keratopathy. The mean corrected distance visual acuity (CDVA) was 1.00 +/- 0.12 logMAR (SD) preoperatively and 0.24 +/- 0.16 logMAR 12 months postoperatively. Before DSEK, corneas with bullous keratopathy had higher total HOAs compared with those in controls (p<0.05). There were no significant differences in anterior surface HOAs between preoperatively and 12 months (p>0.05). CONCLUSIONS: Postoperative CDVA correlated with irregularity of the corneal anterior surface. Corneal anterior HOAs are higher in patients with bullous keratopathy than in controls, and remain higher through 12 months after DSEK. In addition to corneal transparency, regularity of the corneal anterior surface is an important factor in visual acuity after DSEK. PMID- 26541105 TI - The status of glaucoma diagnostics and care in Europe in 2015: a European survey. AB - PURPOSE: To evaluate the current status of glaucoma diagnostics and care in Europe. METHODS: A questionnaire addressing glaucoma patient organizations, resident education, access to an ophthalmologist, use and reimbursement of techniques/instruments for glaucoma diagnostics and follow-up, prescription rules, and glaucoma drug reimbursement was sent to all national representatives of the European Glaucoma Society (EGS) in 2015. The country-specific responses were analyzed and summarized. RESULTS: Completed questionnaires were returned for 24 countries. In 2015, a glaucoma patient organization is functioning in 57% of the respondent countries. Waiting time for an ophthalmology resident position varies between <=6 months and >2 years. The duration of ophthalmology resident training varies between 3 and 7 years. Nonemergency access to an ophthalmologist is available directly in 45.8% and via the general practitioner in 25% of the countries. Disc photography/imaging is always done during glaucoma diagnostics in 9.5% and for follow-up in 55.5% of the respondent countries. Initial therapy of glaucoma is medical in 100% (monotherapy in 91.3%) of the respondent countries. Clinical and visual field examination but not disc photography/imaging is reimbursed in 47.5% of the countries, while in another 47.5% all examinations are reimbursed. Dispensing of the prescribed original eyedrops by the pharmacists is mandatory in 43.5% of the countries, while the aut idem rule applies in 52.2%, and the aut simile rule in 4.3%. CONCLUSIONS: Diagnostics, treatment, and follow up of glaucoma remains diverse in Europe. The differences are due to financial/reimbursement differences. When reimbursement allows, the EGS Guidelines are followed. PMID- 26541106 TI - Retinal vessel diameter changes in different severities of diabetic retinopathy by SD-OCT. AB - PURPOSE: To evaluate retinal vessel diameters in relation to different severity grades of diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Patients with varying degrees of nonproliferative DR (NPDR) underwent circular OCT scans centered on the optic nerve head using a SD-OCT. These cases were retrospectively reviewed. The presence and severity of DR was assessed using Early Treatment Diabetic Retinopathy Study protocols. The 5 largest retinal arterioles and venules were labeled and measured on OCT scans for each patient according to previously published methods. Vertical vessel inner contour diameter, vertical vessel outer contour diameter, and reflectance shadowing width were among the documented parameters. RESULTS: Of 59 eyes from 45 patients examined, 30 (50.2%) and 29 (49.8%) had mild and severe NPDR, respectively. Eyes with severe NPDR had narrower mean arteriolar vertical vessel inner diameter (87.9 +/- 10.8 MUm), vertical vessel outer diameter (119.1 +/- 9.7 MUm), and vessel shadow width (78.8 +/- 10.9 MUm) than eyes with mild NPDR (89.8 +/- 12.1 MUm, 120.9 +/- 12.9 MUm, 81.3 +/- 15.3 MUm). However, the differences were not statistically significant (p = 0.53, 0.55, 0.47). No correlation was shown between the severity of NPDR and arteriolar parameters (p = 0.31, 0.59, 0.75). Wider venular diameters were associated with increasing severity of NPDR (p<0.001, <0.001, 0.007, respectively). The association remained after multivariate adjustment for age, sex, eye, and cataract surgery (p = 0.04, 0.01, 0.007, respectively). CONCLUSIONS: Wider retinal venule diameter was significantly associated with the severity of NPDR by SD-OCT-assisted measurement. Prospective studies would be needed to evaluate whether change in retinal venule could be used as a clinical indicator of DR progression. PMID- 26541107 TI - Late opacification of a hydrophilic acrylic intraocular lens in Europe. AB - PURPOSE: To describe the clinical and microscopic findings in 2 different patients of 2 cases of late opacification of the hydrophilic acrylic intraocular lens (IOL) Ioflex. METHODS: Two eyes of 2 patients (73 and 74 years old) had an uneventful phacoemulsification surgery with implantation of the Ioflex IOL (power +21.5 D). At 5 years after surgery, a dense IOL opacification was detected in both cases with significant visual degradation. The IOLs were explanted and analyzed by microscopy. RESULTS: In both cases, a satisfactory visual recovery was achieved (corrected distance visual acuity of 6/9 and 6/12). Microscopic examination of the explanted IOLs revealed multiple small granules on the surface/subsurface of the lens. Although histochemical or surface analyses were not performed, the aspect appears consistent with a process of calcification of this lens design. Other findings included few surface contaminants, such as fibers, crystals that may correspond to dry viscoelastic and/or salt solutions, as well as pigments and dust-like deposits. CONCLUSIONS: Opacification of the posterior chamber hydrophilic acrylic IOL Ioflex probably related to calcification can appear several years after its implantation and requires IOL exchange due to the significant visual loss induced. More studies are required to understand the causes of this complication. PMID- 26541108 TI - Comparison of astigmatism correction using either peripheral corneal relaxing incisions or toric intraocular lenses. AB - PURPOSE: To compare the efficacy and short-term stability of toric intraocular lenses (tIOL) and peripheral cornea relaxing incisions (PCRI) during phacoemulsification. METHODS: Patients with preexisting corneal astigmatism had cataract surgery either with tIOL (AcrySof Toric) (39 eyes of 35 patients) or standard intraocular lens (AcrySof) + PCRIs (38 eyes of 33 patients). Patients were retrospectively evaluated for manifest refraction, corneal topography, and uncorrected and corrected visual acuities preoperatively and at postoperative 1 and 6 months. The Alpins vectorial method was used to analyze the target induced astigmatism (TIA) and surgically induced astigmatism (SIA), magnitude of error (the difference between the magnitude of SIA and TIA) (ME), and correction index. RESULTS: Mean preoperative corneal astigmatism was 2.21 +/- 1.32 D in the tIOL group and 2.24 +/- 0.96 D in the PCRI group; the difference was not significant. The decrease in astigmatism was significant in both groups at last follow-up (64% tIOL group, 32% PCRI group, p<0.01, Wilcoxon signed rank test). The mean remaining refractive astigmatism was significantly higher in the PCRI group than in the tIOL group at 1-month (1.42 +/- 1.22, 0.89 +/- 0.68, respectively) and 6 month follow-ups (1.75 +/- 1.37 D, 0.92 +/- 0.72, respectively) (p<0.01). The mean ME was significantly lower (-0.35 versus -0.88) with a higher correction index (0.96 versus 0.56) in the tIOL group at 6 months postoperatively. CONCLUSIONS: Both tIOL implantation and using PCRI were effective methods to reduce preoperative astigmatism at the time of the cataract surgery. However, tIOLs provided better remaining astigmatism with a more stable refraction than PCRI. PMID- 26541109 TI - Influence of hyperopia and amblyopia on choroidal thickness in children. AB - PURPOSE: To compare subfoveal choroidal thicknesses (ChTs) of anisometropic hyperopic amblyopic, hyperopic nonamblyopic, and emmetropic control eyes and to investigate the associations between ChT and ambylopia, spherical equivalent (SE), and axial length in the pediatric population. METHODS: Forty-six hyperopic nonamblyopic (hyperopic group), 33 anisometropic hyperopic amblyopic (amblyopic group), and 42 emmetropic (emmetropic group) eyes were enrolled in this cross sectional comparative study. Enhanced depth imaging spectral-domain optical coherence tomography was used for quantitative analysis of subfoveal ChT. ChT was quantified manually as the distance between the hyperreflective line corresponding to the retinal pigment epithelium and the chorioscleral interface at the subfoveal area. RESULTS: The mean age was 10.6 +/- 3.3 years (range 5-17) in the hyperopic group, 10.7 +/- 3.3 years (range 5-17) in the amblyopic group, and 11.2 +/- 3.3 years (range 5-17 years) in the emmetropic group (p = 0.627). The hyperopic and amblyopic groups had significantly thicker choroid compared to the emmetropic group (p1 = 0.005 and p2 = 0.006, respectively). However, there was no significant difference between the hyperopic and amblyopic groups concerning subfoveal ChT (p = 0.857). In addition, covariance analysis showed that although SE was independently associated with subfoveal ChT (p = 0.014), amblyopia had no significant independent effect on subfoveal ChT (p = 0.671). Further, subfoveal ChT had weak correlations with the axial length (r = -0.297, p = 0.001) and SE (r = 0.274, p = 0.002). CONCLUSIONS: Hyperopia was associated with subfoveal ChT, whereas amblyopia had no independent significant effect on subfoveal ChT in our study population. PMID- 26541111 TI - Long-term anatomical and functional results in patients undergoing observation for idiopathic nontractional epiretinal membrane. AB - PURPOSE: To evaluate the anatomical and functional course without surgical intervention in patients with nontractional epiretinal membrane (ERM) using spectral-domain optical coherence tomography (SD-OCT) in a long-term follow-up of 38.2 +/- 30.6 months. METHODS: Participants were 58 patients with nontractional ERM, which was defined as a tear or rip of the ERM in at least one line of OCT scan. All patients were observed without any surgical intervention. All patients underwent ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement, funduscopy, and SD-OCT. Routine follow-up visits were performed every 6 months or earlier at the discretion of the investigator. RESULTS: There was no statistically significant difference in BCVA or central foveal thickness (CFT) at all time points of the follow-up. About 84.4% of patients presented improvement or stabilization in BCVA at the end of the follow up, while 53.4% of patients had a decrease in CFT. All patients had intact ellipsoid zone and none of them needed surgical intervention at the end of the follow-up of 38.2 +/- 30.6 months. CONCLUSIONS: In patients with nontractional ERM, BCVA and CFT may remain stable in a long-term follow-up. Therefore, if ellipsoid zone is intact and there is a tear or rip of ERM in at least one OCT scan, patients can be monitored and surgery may be deferred because of high percentage of structural and functional stability. PMID- 26541110 TI - Rotational stability and patient satisfaction after implantation of a new toric IOL. AB - PURPOSE: To evaluate rotational stability, astigmatism correction, visual outcomes, and patient satisfaction after implantation of the toric intraocular lens (IOL) Torica-aA following cataract extraction over a 6-month follow-up period. METHODS: This prospective observational study enrolled 40 eyes of 26 patients presenting with preexisting corneal astigmatism of 1.00 to 2.60 D. The rotational stability of the IOL was evaluated using retroillumination photographs taken within 24 hours after surgery and 1 week and 6 months postoperatively. Other main study outcomes were assessed 6 months postoperatively and included uncorrected and distance-corrected visual acuities, astigmatism correction, and patient satisfaction. RESULTS: Six months postoperatively, mean absolute IOL rotation was 1.99 +/- 1.88 degrees (range 0.10-7.40 degrees ) and secondary repositioning was not required. The IOL rotation was <3 degrees in 85% of eyes, <=5 degrees in 94% of eyes, and <8 degrees in 100% of eyes. Mean residual refractive cylinder was -0.57 +/- 0.34 D. The magnitude of the J0 vector was significantly decreased postoperatively (p<0.0001). The mean J45 vector was close to zero preoperatively and postoperatively (p = 0.27). Mean monocular uncorrected distance visual acuity (UDVA) was 0.09 +/- 0.12 logMAR and 97% of eyes achieved UDVA of 20/40 or better including 66% of eyes having 20/25 or better. The good UDVA resulted in high levels of spectacle independence and patient satisfaction. CONCLUSIONS: Implantation of the Torica-aA IOL was safe and effective in reducing low to moderate preexisting corneal astigmatism and provided good rotational stability and refractive outcomes, which led to a high degree of patient satisfaction. PMID- 26541112 TI - Bilateral optic disc edema as a presentation of an obstructing spinal plasmacytoma. AB - PURPOSE: To report a rare case of bilateral optic disc edema as presentation of an obstructing spinal plasmacytoma. METHODS: Case report. RESULTS: A 41-year-old healthy man presented with distortion of his peripheral vision for 9 months. He denied headaches or neurologic symptoms. Examination showed bilateral optic disc swelling, radial disc hemorrhages, and absent spontaneous venous pulsations. Brain magnetic resonance imaging (MRI) and magnetic resonance venography were unrevealing. Lumbar puncture showed a normal opening pressure of 19 cm cerebrospinal fluid (CSF). CSF protein was significantly elevated at 3.22 g/L (0.10-0.45 g/L). Spinal MRI with contrast revealed a tumor in the T9 vertebral body extending through the disc spaces into T8 and T10, compressing the spinal cord. Computed tomography-guided biopsy confirmed a spinal plasmacytoma. He received radiotherapy to the spine T7-T11 to reduce spinal cord compression followed by a 6-month course of chemotherapy with dexamethasone, cyclophosphamide, and thalidomide. Disc swelling improved on starting radiotherapy with complete resolution 8 months posttreatment. MRI spine showed reduction of tumor. CONCLUSIONS: This case highlights the importance of spinal imaging in patients with normal cranial scans and raised CSF protein levels who lack the typical idiopathic intracranial hypertension phenotype. PMID- 26541113 TI - Predicting cataract surgery time based on preoperative risk assessment. AB - PURPOSE: Operating room (OR) time is an expensive resource that should be optimized to reduce costs. Individualpreoperative risk parameters (PORS) assessment may aid in predicting cataract surgery time. METHODS: Dedicated software was developed and known risk factors for cataract surgery were integrated into it.Preoperative risk parameters were assigned to each patient in the preoperative meeting and the risk score wascalculated. A total of 153 patients were divided according to a standard classification into low-risk group (PORS<=2) and high-risk group (PORS >5). Duration of surgery for each group was compared by Student t test and linearregression analysis was used to calculate the relation between change in OR time and change in risk score. RESULTS: Patients in the high PORS group had longer surgery times when compared with patients in the low PORSgroup (37.6 vs 19.6, p<0.001). Risk scores positively correlated with surgery time (r = 0.30, p<0.001). Predictionequations for the OR time demonstrated for 2 surgeons that every increase in 1 risk point added 2.2 or 3.3 minutesto the OR time. Outliers (more than 1 standard deviation [SD] from each surgeon's surgery mean time) hadmore than twice the risk score of cases within 1 SD from the mean. CONCLUSIONS: The PORS system may be a useful tool for predicting OR time based on individual patient risk andmay improve OR scheduling. PMID- 26541114 TI - Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization. AB - PURPOSE: Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. METHODS: We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. RESULTS: The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. CONCLUSIONS: Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections. PMID- 26541115 TI - Estimation of depression prevalence in patients with Stargardt disease using PHQ 9 and Zung scores. AB - PURPOSE: To evaluate the psychological impact and depression prevalence in patients with Stargardt disease. METHODS: We conducted a case-control study including 39 patients with Stargardt disease and 32 age- and sex-matched healthy controls. All participants underwent a complete ophthalmologic examination and completed the Patient Health Questionnaire-9 (PHQ-9) and the Zung Depression Inventory questionnaire. Results were analyzed using IBM SPSS 22.0 software. RESULTS: The patient group consisted of 19 men and 20 women with mean age of 36.9 +/- 5.4 years and control group of 19 men and 13 women with mean age of 42.5 +/- 10.1 years. The mean values of PHQ-9 and Zung scores for patients and healthy individuals were 10.9 +/- 4.9, 46.7 +/- 11.1, 6.7 +/- 5.4, and 41.1 +/- 8.5, respectively. There were statistically significant differences between the 2 groups in PHQ-9 scores (independent samples t test: p = 0.001), but not in Zung scores (Mann-Whitney test: p = 0.053). The PHQ-9 and Zung scores appeared to be moderately but significantly correlated (Pearson coefficient 0.44, p<0.0001). In addition, PHQ-9 score seems to be raised along with age, whereas both scores are low when best-corrected visual acuity is high. CONCLUSIONS: Patients with Stargardt disease exhibited more depressive symptoms compared to healthy individuals according mainly to PHQ-9 scores. Moderate depression was significantly correlated visual function decline. PMID- 26541116 TI - Preparing non-volatile resistive switching memories by tuning the content of Au@air@TiO2-h yolk-shell microspheres in a poly(3-hexylthiophene) layer. AB - Crystalline hybrid microspheres, encapsulating a Au nanocore in the hollow cavity of a hairy semiconductor TiO2 shell (Au@air@TiO2-h microspheres) were prepared using template-assisted synthesis methods. The as-prepared microspheres are dispersed into a poly(3-hexylthiophene) (P3HT) matrix and used as a memory active layer. The electrical rewritable memory effects of Al/[Au@air@TiO2-h + P3HT]/ITO sandwich devices can be effectively and exactly controlled by tuning the microsphere content in the electroactive layer. To clarify the switching mechanism, different components in the device, such as P3HT and the microspheres, have been investigated. And it was determined that the switching mechanism can be attributed to the formation and rupture of oxygen vacancy filaments. These results suggest that the Au@air@TiO2-h microspheres are potentially capable of high density data storage. In addition, this finding could provide important guidelines for the reproducibility of nanocomposite-based memory devices and is helpful to demonstrate the switching mechanism of these devices. PMID- 26541117 TI - X-ray absorption, phase and dark-field tomography through a beam tracking approach. AB - We present a development of the beam-tracking approach that allows its implementation in computed tomography. One absorbing mask placed before the sample and a high resolution detector are used to track variations in the beam intensity distribution caused by the sample. Absorption, refraction, and dark field are retrieved through a multi-Gaussian interpolation of the beam. Standard filtered back projection is used to reconstruct three dimensional maps of the real and imaginary part of the refractive index, and of the dark-field signal. While the method is here demonstrated using synchrotron radiation, its low coherence requirements suggest a possible implementation with laboratory sources. PMID- 26541118 TI - Consideration of Out-of-Office Blood Pressure Monitoring in Hypertension Management. PMID- 26541119 TI - A differential protein solubility approach for the depletion of highly abundant proteins in plasma using ammonium sulfate. AB - Depletion of highly abundant proteins is an approved step in blood plasma analysis by mass spectrometry (MS). In this study, we explored a precipitation and differential protein solubility approach as a fractionation strategy for abundant protein removal from plasma. Total proteins from plasma were precipitated with 90% saturated ammonium sulfate, followed by differential solubilization in 55% and 35% saturated ammonium sulfate solutions. Using a four hour liquid chromatography (LC) gradient and an LTQ-Orbitrap XL mass spectrometer, a total of 167 and 224 proteins were identified from the 55% and 35% ammonium sulfate fractions, whereas 235 proteins were found in the remaining protein fractions with at least two unique peptides. SDS-PAGE and exclusive total spectrum counts from LC-MS/MS analyses clearly showed that majority of the abundant plasma proteins were solubilized in 55% and 35% ammonium sulfate solutions, indicating that the remaining protein fraction is of potential interest for identification of less abundant plasma proteins. Serum albumin, serotransferrin, alpha-1-antitrypsin and transthyretin were the abundant proteins that were highly enriched in 55% ammonium sulfate fractions. Immunoglobulins, complement system proteins, and apolipoproteins were among other abundant plasma proteins that were enriched in 35% ammonium sulfate fractions. In the remaining protein fractions a total of 40 unique proteins were identified of which, 32 proteins were identified with at least 10 exclusive spectrum counts. According to PeptideAtlas, 9 of these 32 proteins were estimated to be present at low MUg ml( 1) (0.12-1.9 MUg ml(-1)) concentrations in the plasma, and 17 at low ng ml(-1) (0.1-55 ng ml(-1)) range. PMID- 26541120 TI - Primary renal neuroblastoma with metastasis and matrix metalloproteinase-14 expression. AB - We herein report the rare case of a 4-year-5-month-old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase-9 and -14 (MMP-9 and MMP-14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP-9 expression was not observed, but MMP-14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP-14 staining in other cases, expression of MMP-14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP-14 expression in the primary tumor might metastasize and form MMP-14-rich lesions. PMID- 26541121 TI - Electrocardiographic and Electrophysiological Characteristics of Atrial Tachycardia With Early Activation Close to the His-Bundle. AB - INTRODUCTION: Radiofrequency (RF) ablation of atrial tachycardia (AT) with earliest activation at the His-bundle may be associated with the risk of AV block, and detection of this AT origin using the electrocardiogram (ECG) would be helpful in planning ablation. Aim of this study was to characterize the P-wave morphology and intracardiac electrograms at the successful ablation site for this group of ATs. METHODS: All consecutive patients undergoing ablation for AT with earliest activation at the His-bundle were included. Twelve-lead ECG and intracardiac electrograms were analyzed. RESULTS: A total of 33 patients underwent successful ablation. The P-wave and the PR interval during AT (cycle length 460 +/- 88, range 360-670 milliseconds) were significantly shorter compared to sinus rhythm 87 +/- 18 vs. 117 +/- 23 and 131 +/- 37 vs. 170 +/- 47 milliseconds, respectively, P < 0.01. In 28 patients (85%), the P-wave was biphasic (-/+) or triphasic (+/-/+) in the precordial leads, especially V4 -V6 , and in 25 patients (76%) it was biphasic (-/+) or triphasic (+/-/+) in the inferior leads. RF was delivered at the following locations: noncoronary aortic cusp (NCC) in 24 patients, antero-septal left atrium in 4, supero-septal right atrium in 3, left coronary cusp in 1, and between the right coronary cusp and the NCC in 1. Atrial bipolar electrograms at the successful ablation site preceded the P-wave by 38 +/- 11 (range 10-60) milliseconds, and AT termination was obtained after a mean RF energy time of 10 +/- 8 (range 2-31) seconds. CONCLUSION: A characteristic narrow and biphasic (-/+) or triphasic (+/-/+) P wave in the inferior and precordial leads reliably identifies the group of AT arising from the para-Hisian region. PMID- 26541122 TI - Evidence Levels: Applied to Select Fall and Fall Injury Prevention Practices. AB - PROBLEM: Rehabilitation nurses know the impact of injury on function, independence, and quality of life, complicated by age-related changes associated with decreased strength, endurance, reserve, frailty, and social and financial resources. Multidisciplinary teams are essential to provide expert, age specific health care delivery to this vulnerable population across settings of care. PURPOSE: The purpose of this article is to apply level of evidence rating scales to identify the best practice interventions to prevent falls on rehabilitation units. KEY FINDINGS AND CLINICAL RELEVANCE: The evidence supports the importance of determining specific risk factors and initiating multifactorial fall risk factors tailored to the individual. Yet, little evidence exists for single interventions, universal fall prevention strategies, and population-specific fall prevention strategies. A review of the literature confirms the effectiveness of many fall prevention practices and interventions remains insufficient. Of particular concern are rehabilitation units in hospitals that have higher fall rates compared to other acute units. PMID- 26541123 TI - Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection. AB - Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4.7 (sd 1.6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31.8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value=0.01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1.83; 95 % CI 1.12, 2.99; P trend=0.02), but not in men (AHR 0.96; 95 % CI 0.76, 1.22; P trend=0.73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4.04; 95 % CI 1.42, 11.5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality. PMID- 26541124 TI - Calculating New Parameters. PMID- 26541125 TI - Right Time, Right Place: Probing the Functions of Organelle Positioning. AB - The proper spatial arrangement of organelles underlies many cellular processes including signaling, polarization, and growth. Despite the importance of local positioning, the precise connection between subcellular localization and organelle function is often not fully understood. To address this, recent studies have developed and employed different strategies to directly manipulate organelle distributions, such as the use of (light-sensitive) heterodimerization to control the interaction between selected organelles and specific motor proteins, adaptor molecules, or anchoring factors. We review here the importance of subcellular localization as well as tools to control local organelle positioning. Because these approaches allow spatiotemporal control of organelle distribution, they will be invaluable tools to unravel local functioning and the mechanisms that control positioning. PMID- 26541126 TI - Changing Platitudes to Attitudes: Making the Imaging 3.0 Culture Stick. PMID- 26541127 TI - Speaking of Language Revisited. PMID- 26541128 TI - Archive or Discard Computer-Aided Detection Markings: Two Schools of Thought. PMID- 26541129 TI - Authors' Reply. PMID- 26541131 TI - Can We Score 100 in the Merit-Based Incentive Payment System? PMID- 26541130 TI - ACR Appropriateness Criteria Acute Trauma to the Knee. AB - More than 500,000 visits to the emergency room occur annually in the United States, for acute knee trauma. Many of these are twisting injuries in young patients who can walk and bear weight, and emergent radiographs are not required. Several clinical decision rules have been devised that can considerably reduce the number of radiographs ordered without missing a clinically significant fracture. Although a fracture is seen on only 5% of emergency department knee radiographs, 86% of knee fractures result from blunt trauma. In patients with a fall or twisting injury who have focal tenderness, effusion, or inability to bear weight, radiographs should be the first imaging study obtained. If the radiograph shows no fracture, MRI is best for evaluating for a suspected meniscus or ligament tear, or the injuries from a reduced patellar dislocation. Patients with a knee dislocation should undergo radiographs and an MRI, as well as an angiographic study such as a fluoroscopic, CT, or MR angiogram. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures, by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 26541132 TI - Implementing an Electronic Event-Reporting System in a Radiation Oncology Department: The Effect on Safety Culture and Near-Miss Prevention. AB - PURPOSE: We implemented an electronic event-reporting system to investigate its effect on quality improvement in our department. METHODS: We developed an event reporting program that launched in October 2012; data analysis was performed in January 2014. Events were logged by the radiation oncology staff and reviewed by our quality and safety committee on a biweekly basis. To measure the efficacy of the new program, and change in safety culture, a Likert-scale survey was administered before, and three months after, implementation of the event reporting system. RESULTS: A total of 194 events were logged into the new system during a 15-month period (approximately 13 events per month), compared with 93 events in an 18-month period (approximately five events per month) before the program was launched. The average number of events reported by radiation therapists increased from 0.9 per month to 8.6 per month. The survey results showed a shift toward stronger agreement by staff members, in postimplementation versus preimplementation responses, when they were asked if they knew how to report an event in the department (P = .042), and if the current event-reporting system would reduce the incidence of future events (P = .032). Results showed a trend toward stronger agreement by staff members when they were asked if they felt more comfortable reporting events that they had observed (P = .093). Multiple safety action plans were implemented as a result of analysis of these events. CONCLUSIONS: An electronic event-reporting system streamlines quality and safety in a radiation oncology department by increasing reported events and promoting a safety culture. A program that is widely accessible, easy to use, and can analyze data meaningfully will be the most successful. PMID- 26541133 TI - Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes. AB - OBJECTIVE: ZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries. METHODS: We screened HLA-A2 restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice and in vivo CTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2 restricted T1D patients. RESULTS: We demonstrated that ZnT8(107-116)(115), ZnT8(110-118), and ZnT8(177-186) were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8(107-116)(115), ZnT8(115-123), ZnT8(153-161), ZnT8(177-186) and ZnT8(291-300) represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients. CONCLUSIONS: The differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention. PMID- 26541136 TI - Corrigendum: Communication activity in a social network: relation between long term correlations and inter-event clustering. PMID- 26541134 TI - Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity. AB - BACKGROUND: Young infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds. METHODS: Two cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1-6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children. RESULTS: Antibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1 19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association. CONCLUSION: The antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens. PMID- 26541135 TI - Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy. AB - Pulmonary tuberculosis (TB) remains one of the leading causes of infectious disease death despite widespread usage of the BCG vaccine. A number of new TB vaccines have moved into clinical evaluation to replace or boost the BCG vaccine including ID93+GLA-SE, an adjuvanted subunit vaccine. The vast majority of new TB vaccines in trials are delivered parenterally even though intranasal delivery can augment lung-resident immunity and protective efficacy in small animal models. Parenteral immunization with the adjuvanted subunit vaccine ID93+GLA-SE elicits robust TH1 immunity and protection against aerosolized Mycobacterium tuberculosis in mice and guinea pigs. Here we describe the immunogenicity and efficacy of this vaccine when delivered intranasally. Intranasal delivery switches the CD4 T cell response from a TH1 to a TH17 dominated tissue-resident response with increased frequencies of ID93-specific cells in both the lung tissue and at the lung surface. Surprisingly these changes do not affect the protective efficacy of ID93+GLA-SE. Unlike intramuscular immunization, ID93+GLA does not require the squalene-based oil-in-water emulsion SE to elicit protective CD4 T cells when delivered intranasally. Finally we demonstrate that TNF and the IL-17 receptor are dispensable for the efficacy of the intranasal vaccine suggesting an alternative mechanism of protection. PMID- 26541137 TI - Unsettled teamwork: communication and learning in the operating theatres of an urban hospital. AB - AIM: To explore the unsettling effects of increased mobility of nurses, surgeons and other healthcare professionals on communication and learning in the operating theatre. BACKGROUND: Increasingly, healthcare professionals step in and out of newly formed transient teams and work with colleagues they have not met before, unsettling previously relatively stable team work based on shared, local knowledge accumulated over significant periods of close collaboration. DESIGN: An ethnographic case study was conducted of the operating theatre department of a major teaching hospital in London. METHOD: Video recordings were made of 20 operations, involving different teams. The recordings were systematically reviewed and coded. Instances where difficulties arose in the communication between scrub nurse and surgeons were identified and subjected to detailed, interactional analysis. FINDINGS: Instrument requests frequently prompted clarification from the scrub nurse (e.g. 'Sorry, what did you want?'). Such requests were either followed by a relatively elaborate clarification, designed to maximize learning opportunities, or a by a relatively minimal clarification, designed to achieve the immediate task at hand. CONCLUSIONS: Significant variation exists in the degree of support given to scrub nurses requesting clarification. Some surgeons experience such requests as disruptions, while others treat them as opportunities to build shared knowledge. PMID- 26541138 TI - Effect of baclofen on gastric acid pocket in subjects with gastroesophageal reflux disease symptoms. AB - Postprandial gastroesophageal reflux (PGER) in the distal esophagus (DE) is associated with a gastric juice 'acid pocket' (AP). Baclofen reduces AP extension into the DE in healthy volunteers, in part through increased lower esophageal sphincter (LES) pressure. We aimed to verify whether baclofen also affects postprandial AP location and extent in gastroesophageal reflux disease (GERD) patients. Thirteen treatment-naive heartburn-prevalent GERD patients underwent two AP studies, after pretreatment with baclofen 40 mg or placebo 30 minutes preprandially. We performed pH-probe stepwise pull-throughs (PT) (1 cm/min, LES 10 to +5 cm) before and every 30 minutes from 30 minutes before up to 150 minutes after a test meal. After the meal, both after placebo and baclofen, gastric pH significantly dropped at 30, 60, 90 minutes postprandially (P: nadir pHs of 3.9 +/- 0.6, 2.3 +/- 0.6, 2.1 +/- 0.4; B: nadir pHs of 2.5 +/- 0.4, 2.8 +/- 0.4, 2.5 +/- 0.3; all P < 0.05). After placebo, LES pressure decreased at 60, 90 and 120 minutes postprandially (32.7 +/- 6.1 vs. 24.5 +/- 3.1, 27.3 +/- 5.9, 27.3 +/- 6.0 mmHg; analysis of variance [ANOVA], P = 0.037), but this was prevented by baclofen (25.4 +/- 3.4 vs. 29.4 +/- 2, 32.2 +/- 1.4, 35.5 +/- 1.7 mmHg, ANOVA, P = not significant (NS)). Baclofen did not significantly decrease the postprandial AP extent above the LES but prevented the postprandial increase in transient lower esophageal sphincter relaxations (TLESRs) (preprandial vs. postprandial, placebo: 1.1 +/- 0.3 vs. 3.7 +/- 0.7, P < 0.05; baclofen: 1.4 +/- 0.4 vs. 2 +/- 0.5, P = NS). In GERD patients, baclofen significantly increases postprandial LES pressure, prevents the increase TLESRs but, unlike in healthy volunteers, does not affect AP extension into the DE. PMID- 26541139 TI - Erratum to: Communities of practice for supporting health systems change: a missed opportunity. PMID- 26541140 TI - Freiburg Neuropathology Case Conference. A Mass Lesion of the Fourth Ventricle. PMID- 26541141 TI - Prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression from non-small cell lung cancer. AB - BACKGROUND: The aim of this study was to develop a scoring system for prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed nine preoperative characteristics for survival in a series of 64 patients with NSCLC who were operated with posterior decompression and spine stabilization for MSCC. Characteristics significantly associated with survival on multivariate analysis were included in the scoring system. The scoring point for each significant characteristic was derived from the hazard ratios on Cox proportional hazards model. The total score for each patient was obtained by adding the scoring points of all significant characteristics. RESULTS: Eastern Cooperative Oncology Group (ECOG) performance status, number of involved vertebrae, visceral metastases, and time developing motor deficits had significant impact on survival on multivariate analysis and were included in the scoring system. According to the prognostic scores, which ranged from 4 to 10 points, three prognostic groups were designed: 4-5 points (n = 22), 6-7 points (n = 23), and 8-10 points (n = 19). The corresponding 6-month survival rates were 95, 47 and 11%, respectively (P < 0.0001). In addition, the functional outcome was worse in the group of patients with 8-10 points compared with other two prognostic groups. CONCLUSIONS: The new scoring system will enable physicians to identify patient with MSCC from NSCLC who may be a candidate for decompression and spine stabilization, more radical surgery, or supportive care alone. Patients with scores of 4-5, who have the most favorable survival prognosis and functional outcome, can be treated with more radical surgery in order to realize better local control of disease and prevent the occurrence of local disease. Patients with scores of 6-7 points should be surgical candidates, because survival prognosis and functional outcome are acceptable after surgery, while patients with scores of 8-10 points, who have the shortest survival time and poorest functional outcome after surgery, appear to be best treated with radiotherapy or best supportive care. PMID- 26541142 TI - Archetype relational mapping - a practical openEHR persistence solution. AB - BACKGROUND: One of the primary obstacles to the widespread adoption of openEHR methodology is the lack of practical persistence solutions for future-proof electronic health record (EHR) systems as described by the openEHR specifications. This paper presents an archetype relational mapping (ARM) persistence solution for the archetype-based EHR systems to support healthcare delivery in the clinical environment. METHODS: First, the data requirements of the EHR systems are analysed and organized into archetype-friendly concepts. The Clinical Knowledge Manager (CKM) is queried for matching archetypes; when necessary, new archetypes are developed to reflect concepts that are not encompassed by existing archetypes. Next, a template is designed for each archetype to apply constraints related to the local EHR context. Finally, a set of rules is designed to map the archetypes to data tables and provide data persistence based on the relational database. RESULTS: A comparison study was conducted to investigate the differences among the conventional database of an EHR system from a tertiary Class A hospital in China, the generated ARM database, and the Node + Path database. Five data-retrieving tests were designed based on clinical workflow to retrieve exams and laboratory tests. Additionally, two patient-searching tests were designed to identify patients who satisfy certain criteria. The ARM database achieved better performance than the conventional database in three of the five data-retrieving tests, but was less efficient in the remaining two tests. The time difference of query executions conducted by the ARM database and the conventional database is less than 130 %. The ARM database was approximately 6-50 times more efficient than the conventional database in the patient-searching tests, while the Node + Path database requires far more time than the other two databases to execute both the data-retrieving and the patient searching tests. CONCLUSIONS: The ARM approach is capable of generating relational databases using archetypes and templates for archetype-based EHR systems, thus successfully adapting to changes in data requirements. ARM performance is similar to that of conventionally-designed EHR systems, and can be applied in a practical clinical environment. System components such as ARM can greatly facilitate the adoption of openEHR architecture within EHR systems. PMID- 26541143 TI - Metabolomic, enzymatic, and histochemical analyzes of cassava roots during postharvest physiological deterioration. AB - BACKGROUND: Under postharvest physiological deterioration cassava root tubers alter the expression of biosynthetic pathways of certain primary and secondary metabolites, as well as the activity of some scavenging enzymes. Therefore, in this study we hypothesized that cassava cultivars differ as to their physiological responses to deterioration and their biochemical profiles can be an indicative of the tolerance or susceptibility to deterioration. RESULTS: The results corroborate the working hypothesis, revealing that high Levels of phenolic acids, scopoletin, carotenoids, proteins, and augmented activities of guaiacol peroxidase and hydrogen peroxide in non-stored cassava roots can be used as potential biomarkers of cassava deterioration. CONCLUSIONS: Cassava physiological deterioration depends on cultivar and many compounds are up and downregulated during storage time. Secondary metabolites, enzymes, scopoletin, scavenging reactive oxygen species, and acidic polysaccharides are activated as responses to the physiological stress induced in root tubers. PMID- 26541144 TI - Effect of physical activity on sex hormones in women: a systematic review and meta-analysis of randomized controlled trials. AB - INTRODUCTION: Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women. METHODS: Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted. RESULTS: Data suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to -0.03; P = 0.01; I (2) = 0 %) and free estradiol (SMD -0.20; 95 % CI -0.31 to -0.09; P = 0.0005; I (2) = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone-sulfate and adiposity markers, while a significant increase of SHBG was observed. CONCLUSIONS: Although the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women. PMID- 26541145 TI - Surgical treatment of chronic pulmonary aspergillosis using preventive latissimus dorsi muscle flaps. AB - BACKGROUND: Surgery for chronic pulmonary aspergillosis is often technically risky. The choice of immediate thoracoplasty or muscle flap plombage to prevent postoperative space problems remains controversial. This study focused on the use of muscle flaps to prevent postoperative complications. METHODS: During an 8-year period (2004 to 2012), all patients surgically treated for chronic pulmonary aspergillosis were enrolled in this retrospective study. Concomitant intrathoracic transposition of the latissimus dorsi muscle flap has been performed since 2011. The clinical records of these patients were reviewed retrospectively. RESULTS: From 2004 to 2012, 16 patients were treated for chronic pulmonary aspergillosis. Fifteen patients received lobectomies and one had a partial resection. A preventive latissimus dorsi muscle flap was used in 6 patients (37 %). No postoperative deaths occurred. Prolonged air leaks appeared in 2 patients without muscle flaps, resulting in empyema in both. None of the patients with preventive muscle flaps suffered prolonged air leaks and subsequent empyema. In the outpatient clinic, late onset air leaks developed in 2 patients, one of whom had a lobectomy with muscle flap while the other had a lobectomy without muscle flap. Residual pleural space persisted in these two patients and Aspergillus infection later recurred. CONCLUSIONS: Concomitant latissimus dorsi muscle flaps may be effective for the prevention of prolonged air leaks and subsequent empyema. Late onset air leaks are problematic. PMID- 26541146 TI - Comparative assessment of the antirestenotic efficacy of two paclitaxel drug eluting balloons with different coatings in the treatment of in-stent restenosis. AB - BACKGROUND/OBJECTIVES: Preclinical investigations have suggested that coating technology is crucial for the efficacy of drug-eluting balloons (DEB). Aim of this study is to compare the antirestenotic efficacy of two paclitaxel DEB with different coatings in the treatment of in-stent restenosis (ISR) by means of a morphological and functional assessment. METHODS: In a single center, prospective, non-randomized study, the shellac-paclitaxel coated DIOR, and the urea-paclitaxel coated IN.PACT Falcon were compared in the setting of ISR. Quantitative angiography, fractional flow reserve (FFR), and optical coherence tomography (OCT) were performed at baseline, postprocedure and 6-month follow-up. Main endpoints were QCA, FFR and OCT-based parameters of restenosis. RESULTS: Forty-five patients were included, 20 (44 %) received treatment with the DIOR and 25 (56 %) with the IN.PACT Falcon. Angiographic and device success were 100 and 90 % for the DIOR, and 100 and 92 % for the IN.PACT Falcon, respectively. After 6 months, in-segment late lumen loss (-0.03 +/- 0.43 vs. 0.36 +/- 0.48 mm, p = 0.014) and diameter stenosis (30.7 +/- 16.2 vs. 41.3 +/- 22.6 %, p = 0.083) were lower for the IN.PACT Falcon. FFR distal of the stent was significantly higher in the IN.PACT Falcon group (0.92 +/- 0.07 vs. 0.84 +/- 0.13, p = 0.029) and in stent FFR gradient was lower (0.05 +/- 0.05 vs. 0.13 +/- 0.12, p = 0.002). Between postprocedure and follow-up, a 16 % decrease in neointimal volume was observed for the IN.PACT Falcon, while a 30 % increase was observed for the DIOR (p = 0.006). CONCLUSIONS: The IN.PACT Falcon DEB showed higher antirestenotic efficacy than the DIOR in the treatment of ISR, demonstrating that DEB with an excipient-based coating is not equally effective. PMID- 26541148 TI - Distribution, sources, and risks of polycyclic aromatic hydrocarbons in the surface sediments from 28 lakes in the middle and lower reaches of the Yangtze River region, China. AB - As the largest polycyclic aromatic hydrocarbons (PAHs) emission country, China is suffering from severe PAHs pollution. Twenty-eight lakes in the middle and lower reaches of the Yangtze River region (MLYR), where numerous lakes are located in and play very important roles in the development of the local economy and society, were selected to investigate the levels and sources of the PAHs in this region and the related influence factors. Concentrations of the 16 PAHs (?PAHs) in the sediments ranged from 221.0 to 2418.8 ng g(-1) (dry weight). The mean ?PAHs was higher in the lower reaches than in the middle reaches. ?PAHs in the sediments was positively correlated with the local gross domestic product (GDP), which implies that GDP was the key factor to affect the PAHs level in the sediments of study area. According to the composition of 16 PAHs, the 28 lakes were grouped into 3 clusters. Major PAHs sources for the three types of lakes were significantly different, which were biomass combustion, coal combustion, and vehicle/coal source, respectively. The total toxic benzo(a)pyrene equivalent (TEQ(carc)) of the carcinogenic PAHs in the sediments varied from 12.9 to 472.9 ng TEQ(carc) g(-1). Benzo(a)pyrene (BaP) and dibenzo(a,h)anthracene (DaA) were the two main contributors to total TEQ(carc). PMID- 26541149 TI - A stable isotope approach and its application for identifying nitrate source and transformation process in water. AB - Nitrate contamination of water is a worldwide environmental problem. Recent studies have demonstrated that the nitrogen (N) and oxygen (O) isotopes of nitrate (NO3(-)) can be used to trace nitrogen dynamics including identifying nitrate sources and nitrogen transformation processes. This paper analyzes the current state of identifying nitrate sources and nitrogen transformation processes using N and O isotopes of nitrate. With regard to nitrate sources, delta(15)N-NO3(-) and delta(18)O-NO3(-) values typically vary between sources, allowing the sources to be isotopically fingerprinted. delta(15)N-NO3(-) is often effective at tracing NO(-)3 sources from areas with different land use. delta(18)O-NO3(-) is more useful to identify NO3(-) from atmospheric sources. Isotopic data can be combined with statistical mixing models to quantify the relative contributions of NO3(-) from multiple delineated sources. With regard to N transformation processes, N and O isotopes of nitrate can be used to decipher the degree of nitrogen transformation by such processes as nitrification, assimilation, and denitrification. In some cases, however, isotopic fractionation may alter the isotopic fingerprint associated with the delineated NO3(-) source(s). This problem may be addressed by combining the N and O isotopic data with other types of, including the concentration of selected conservative elements, e.g., chloride (Cl(-)), boron isotope (delta(11)B), and sulfur isotope (delta(35)S) data. Future studies should focus on improving stable isotope mixing models and furthering our understanding of isotopic fractionation by conducting laboratory and field experiments in different environments. PMID- 26541150 TI - On the design of a DEA-based device to pot entially assist lower leg disorders: an analytical and FEM investigation accounting for nonlinearities of the leg and device deformations. AB - BACKGROUND: One of the recommended treatments for disorders associated with the lower extremity venous insufficiency is the application of external mechanical compression. Compression stockings and elastic bandages are widely used for the purpose of compression therapy and are usually designed to exert a specified value or range of compression on the leg. However, the leg deforms under external compression, which can lead to undesirable variations in the amount of compression applied by the compression bandages. In this paper, the use of an active compression bandage (ACB), whose compression can be regulated through an electrical signal, is investigated. The ACB is based on the use of dielectric elastomer actuators. This paper specifically investigates, via both analytical and non-linear numerical simulations, the potential pressure the ACB can apply when the compliancy of the human leg is taken into account. The work underpins the need to account for the compressibility of the leg when designing compression garments for lower extremity venous insufficiency. METHODS: A mathematical model is used to simulate the volumetric change of a calf when compressed. Suitable parameters for this calf model are selected from the literature where the calf, from ankle to knee, is divided into six different regions. An analytical electromechanical model of the ACB, which considers its compliancy as a function of its pre-stretch and electricity applied, is used to predict the ACB's behavior. Based on these calf and ACB analytical models, a simulation is performed to investigate the interaction between the ACB and the human calf with and without an electrical stimulus applied to the ACB. This simulation is validated by non-linear analysis performed using a software based on the finite element method (FEM). In all simulations, the ACB's elastomer is stretched to a value in the range between 140 and 220 % of its initial length. RESULTS: Using data from the literature, the human calf model, which is examined in this work, has different compliancy in its different regions. For example, when a 28.5 mmHg (3.8 kPa) of external compression is applied to the entire calf, the ankle shows a 3.7 % of volume change whereas the knee region undergoes a 2.7 % of volume change. The paper presents the actual pressure in the different regions of the calf for different values of the ACB's stretch ratio when it is either electrically activated or not activated, and when compliancy of the leg is either considered or not considered. For example, results of the performed simulation show that about 10 % variation in compression in the ankle region is expected when the ACB initially applies 6 kPa and the compressibility of the calf is first considered and then not considered. Such a variation reduces to 5 % when the initial pressure applied by the ACB reduced by half. CONCLUSIONS: Comparison with non-linear FEM simulations show that the analytical models used in this work can closely estimate interaction between an active compression bandage and a human calf. In addition, compliancy of the leg should not be neglected when either designing a compression band or predicting the compressive force it can exert. The methodology proposed in this work can be extended to other types of elastic compression bandages and garments for biomedical applications. PMID- 26541151 TI - Comparative evaluation of sealing ability and microstructure of MTA and Biodentine after exposure to different environments. AB - OBJECTIVES: The aim of this study was to evaluate the sealing ability and morphological microstructure of Biodentine in comparison to ProRoot mineral trioxide aggregate (MTA) after storage in an acidic environment. MATERIALS AND METHODS: Biodentine and ProRoot MTA were prepared and packed into the canal lumen of dentin disks. Twenty specimens of each material were further randomly divided into two groups according to the storage media: group A: materials with saline as storage medium; group B: materials with citric acid buffered at pH 5.4 as storage medium. The sealing ability was evaluated at 1, 3, 6, and 24 h and 1 or 3 months, using a fluid transport model for quantitative analysis of endodontic microleakage. The morphological microstructures of the materials were also evaluated using scanning electron microscopy. RESULTS: During the first 24 h, MTA showed greater fluid transport values than Biodentine in both environments. At the 3-month measurement, when the materials were stored in saline, MTA showed greater ability to prevent fluid movement than Biodentine (p < 0.0001). However, when the materials were stored in an acidic environment, no statistical significant difference was found after 3 months. After storage in saline, both materials showed an uneven crystalline surface with similar hexagonal crystals. The microstructure of Biodentine changed after exposure to citric acid, showing a relatively smooth surface with more spheroidal crystals. CONCLUSIONS: The exposure to an acidic environment, within the limits of this study, seems to result in morphological changes of Biodentine in a different manner than MTA. MTA shows good ability to prevent fluid movement over time, in both environments. The ability of Biodentine to prevent fluid movement over time was enhanced in the acidic environment. CLINICAL RELEVANCE: The findings of the present study could imply that both materials are indicated for use in an acidic environment. PMID- 26541152 TI - Management Options and Outcomes for Neonatal Hypoplastic Left Heart Syndrome in the Early Twenty-First Century. AB - Without surgical treatment, neonatal hypoplastic left heart syndrome (HLHS) mortality in the first year of life exceeds 90 % and, in spite of improved surgical outcomes, many families still opt for non-surgical management. The purpose of this study was to investigate trends in neonatal HLHS management and to identify characteristics of patients who did not undergo surgical palliation. Neonates with HLHS were identified from a serial cross-sectional analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 2000 to 2012. The primary analysis compared children undergoing surgical palliation to those discharged alive without surgery using a binary logistic regression model. Multivariate logistic regression was conducted to determine factors associated with treatment choice. A total of 1750 patients underwent analysis. Overall hospital mortality decreased from 35.3 % in 2000 to 22.9 % in 2012. The percentage of patients undergoing comfort care discharge without surgery also decreased from 21.2 to 14.8 %. After controlling for demographics and comorbidities, older patients at presentation were less likely to undergo surgery (OR 0.93, 0.91-0.96), and patients in 2012 were more likely to undergo surgery compared to those in prior years (OR 1.5, 1.1-2.1). Discharge without surgical intervention is decreasing with a 30 % reduction between 2000 and 2012. Given the improvement in surgical outcomes, further dialogue about ethical justification of non-operative comfort or palliative care is warranted. In the meantime, clinicians should present families with surgical outcome data and recommend intervention, while supporting their option to refuse. PMID- 26541153 TI - Intra-procedural Bronchoscopy to Prevent Bronchial Compression During Pulmonary Artery Stent Angioplasty. AB - Stenosis of the pulmonary arteries frequently occurs during staged palliation of hypoplastic left heart syndrome and variants, often necessitating stent angioplasty. A complication of stent angioplasty is compression of the ipsilateral mainstem bronchus. Following such a case, we re-evaluated our approach to PA stent angioplasty in these patients. The incident case is described. A retrospective observational study of children and adults with superior (SCPC) and/or total cavopulmonary connection (TCPC) undergoing left pulmonary artery (LPA) stent angioplasty between January 1, 2005 and January 5, 2014 and subsequent chest CT was performed to assess the incidence of bronchial compression. The current strategy of employing bronchoscopy to assess bronchial compression during angioplasty is described with short-term results. Sixty-five children and adults underwent LPA stent angioplasty. Other than the incident case, none had symptomatic bronchial compression. Of the total study population, 12 % had subsequent CT, of which one subject had moderate bronchial compression. To date, seven subjects have undergone angioplasty of LPA stenosis and bronchoscopy. In one case, stent angioplasty was not performed because of baseline bronchial compression, exacerbated during angioplasty. In the rest of cases, mild-moderate compression was seen during angioplasty. Following stent angioplasty, the resultant compression was not worse than that seen on test angioplasty. Bronchial compression is a rare complication of stent angioplasty of the pulmonary arteries in children and adults with SCPC/TCPC. Angioplasty of the region of interest with procedural bronchoscopy can help to identify patients at risk of this complication. PMID- 26541154 TI - Plant-mediated biosynthesis of nanoparticles as an emerging tool against mosquitoes of medical and veterinary importance: a review. AB - Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. Mosquito young instars are usually targeted with organophosphates, insect growth regulators and microbial control agents. Indoors residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have strong negative effects on human health and the environment. Newer and safer tools have been recently implemented to enhance control of mosquitoes. In this review, I focus on characterization, effectiveness, and non-target effects of mosquitocidal nanoparticles synthesized using botanical products (mosquitocidal nanoparticles, MNP). The majority of plant-fabricated MNP are silver ones. The synthesis of MNP is usually confirmed by UV-visualization spectroscopy, followed by scanning electron microscopy or transmission electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction studies. Interestingly, plant-synthesized metal nanoparticles have been reported as effective ovicides, larvicides, pupicides, adulticides, and oviposition deterrents against different mosquito species of medical and veterinary importance. Few parts per million of different MNP are highly toxic against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti, and the filariasis mosquito Culex quiquefasciatus. However, despite the growing number of evidences about the effectiveness of MNP, moderate efforts have been carried out to shed light on their possible non-target effects against mosquito's natural enemies and other aquatic organisms. In the final section, particular attention was dedicated to this issue. A number of hot areas that need further research and cooperation among parasitologists and entomologists are highlighted. PMID- 26541156 TI - Non-genomic regulation and disruption of spermatozoal in vitro hyperactivation by oviductal hormones. AB - During capacitation, motility of mammalian spermatozoon is changed from a state of "activation" to "hyperactivation." Recently, it has been suggested that some hormones present in the oviduct are involved in the regulation of this hyperactivation in vitro. Progesterone, melatonin, and serotonin enhance hyperactivation through specific membrane receptors, and 17beta-estradiol suppresses this enhancement by progesterone and melatonin via a membrane estrogen receptor. Moreover, gamma-aminobutyric acid suppresses progesterone-enhanced hyperactivation through the gamma-aminobutyric acid receptor. These hormones dose dependently affect hyperactivation. Although the complete signaling pathway is not clear, progesterone activates phospholipase C and protein kinases and enhances tyrosine phosphorylation. Moreover, tyrosine phosphorylation is suppressed by 17beta-estradiol. This regulation of spermatozoal hyperactivation by steroids is also disrupted by diethylstilbestrol. The in vitro experiments reviewed here suggest that mammalian spermatozoa are able to respond to effects of oviductal hormones. We therefore assume that the enhancement of spermatozoal hyperactivation is also regulated by oviductal hormones in vivo. PMID- 26541155 TI - Open-loop static and dynamic characteristics of the arterial baroreflex system in rabbits and rats. AB - The arterial baroreflex system is the most important negative feedback system for stabilizing arterial pressure (AP). This system serves as a key link between the autonomic nervous system and the cardiovascular system, and is thus essential for understanding the pathophysiology of cardiovascular diseases and accompanying autonomic abnormalities. This article focuses on an open-loop systems analysis using a baroreceptor isolation preparation to identify the characteristics of two principal subsystems of the arterial baroreflex system, namely, the neural arc from pressure input to efferent sympathetic nerve activity (SNA) and the peripheral arc from SNA to AP. Studies on the static and dynamic characteristics of the two arcs under normal physiological conditions and also under various interventions including diseased conditions are to be reviewed. Quantitative understanding of the arterial baroreflex function under diseased conditions would help develop new treatment strategies such as electrical activation of the carotid sinus baroreflex for drug-resistant hypertension. PMID- 26541157 TI - The PI3K/Akt, p38MAPK, and JAK2/STAT3 signaling pathways mediate the protection of SO2 against acute lung injury induced by limb ischemia/reperfusion in rats. AB - Sulfur dioxide (SO2) is naturally synthesized by glutamate-oxaloacetate transaminase (GOT) from L-cysteine in mammalian cells. We found that SO2 may have a protective effect on acute lung injury (ALI) induced by limb ischemia/reperfusion (I/R) in rats. The PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways are crucial in cell signaling transduction. The present study aims to verify the role of SO2 on limb I/R-induced ALI, and investigate whether PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways were involved, as well as the relationship among the three pathways; we used specific inhibitors (LY294002, SB03580, and Stattic) to block them, respectively. The experimental methods of Western, ELISA, TUNEL, etc., were used to test the results. In the I/R group, the parameters of lung injury (MDA, MPO, TUNEL, cytokines) increased significantly, but the administration of Na2SO3/NaHSO3 attenuated the damage in the lung. The Western results showed that the rat's lung exist expression of P-STAT3, P-AKT, and P-p38 proteins. After I/R, P-STAT3, P-Akt, and P-p38 proteins expression all increased. After using Na2SO3/NaHSO3, P-Akt, and P-p38 proteins expression increased, but P STAT3 protein expression decreased. We also found a strange phenomenon; compared to the I/R + SO2 group, the administration of stattic, P-p38 protein expression showed no change, but P-Akt protein expression increased (p < 0.05). In conclusion, SO2 has a protective effect on rats with limb I/R-induced ALI. The JAK2/STAT3, PI3K/Akt, and p38MAPK pathways are likely all involved in the process, and the JAK2/STAT3 pathway may have an impact on the P13K/Akt pathway. PMID- 26541159 TI - Molecular Approach Coupled with Biochemical Attributes to Elucidate the Presence of DYMV in Leaf Samples of Lablab purpureus. L Genotypes. AB - A laboratory study was delineated to ascertain the impact and the extent of Dolichos yellow mosaic virus (DYMV) on biochemical constituents and various enzyme levels in the leaves of hyacinth bean. DYMV-infected leaves of all the genotypes used in the study revealed significant and consistent changes in activities of CAT, APX, PPO, DHAR, and MDHAR paralleled with a compelling hike in proline levels. Unlike that in non-infected leaves of the genotypes VRSEM-301 and VRSEM-749, VRSEM-894 and VRSEM-855, the enzyme level did not alter much which extended equally with increased phenolics, suggesting a well-coordinated generation of free radicals thereby suppressing oxidative stress in the latter. The genotypes were also evaluated at molecular level for elucidating the presence of the virus by using five sets of primer pairs. Two primers viz., DAC1 and DAC2 witnessed the presence of the virus in both non-infected and infected leaves. The difference in the appearance and/or disappearance of bands according to non infected to infect reverberates the variation between genotypes in defense against infection. PMID- 26541158 TI - Sleep as a biological problem: an overview of frontiers in sleep research. AB - Sleep is a physiological process not only for the rest of the body but also for several brain functions such as mood, memory, and consciousness. Nevertheless, the nature and functions of sleep remain largely unknown due to its extremely complicated nature and lack of optimized technology for the experiments. Here we review the recent progress in the biology of the mammalian sleep, which covers a wide range of research areas: the basic knowledge about sleep, the physiology of cerebral cortex in sleeping animals, the detailed morphological features of thalamocortical networks, the mechanisms underlying fluctuating activity of autonomic nervous systems during rapid eye movement sleep, the cutting-edge technology of tissue clearing for visualization of the whole brain, the ketogenesis-mediated homeostatic regulation of sleep, and the forward genetic approach for identification of novel genes involved in sleep. We hope this multifaceted review will be helpful for researchers who are interested in the biology of sleep. PMID- 26541160 TI - Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a Diverse Therapeutic Target: A Computational Perspective. AB - Adenosine monophosphate-activated protein kinase (AMPK) is viewed as a privileged therapeutic target for several diseases such as cancer, diabetes, inflammation, obesity, etc. In addition, AMPK has entered the limelight of current drug discovery with its evolution as a key metabolic regulator. AMPK also plays a key role in the maintenance of cellular energy homeostasis. Structurally, AMPK is a heterotrimeric protein, which consists of three protein subunits (alpha, beta, and gamma). The crystal structure of AMPK was solved, and several computational studies including homology modeling, molecular docking, molecular dynamics, and QSAR have been reported in order to explore the structure and function of this diverse therapeutic target. In this review, we present a comprehensive up-to-date overview on the computational and molecular modeling approaches that have been carried out on AMPK in order to understand its structure, function, dynamics, and its drug binding landscape. Information provided in this review would be of great interest to a wide pool of researchers involved in the design of new molecules against various diseases where AMPK plays a predominant role. PMID- 26541161 TI - Effect of Drought Stress on Total Phenolic, Lipid Peroxidation, and Antioxidant Activity of Achillea Species. AB - The changes in total phenolic content (TPC), total flavonoid content (TFC), proline, malondialdehyde (MDA), H2O2, and antioxidant activity were assessed based on three model systems in three Achillea species (Achillea millefolium, A. nobilis, and A. filipendulina) growing under four irrigation regimes, including 100% FC (field capacity as normal irrigation) 75% FC (low stress), 50% FC (moderate stress), and 25% FC (severe stress) conditions. The highest TPC (47.13 mg tannic acid/g DW) and TFC (20.86 mg quercetin/g W) were obtained in A. filipendulina under moderate and severe stress conditions. In 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay, the highest and the lowest antioxidant activity was obtained for A. millefolium (70.28%) and A. filipendulina (53.21%), respectively, while in the FTC model system A. nobilis revealed the highest antioxidant activity (1.934) in severe drought condition. In the linoleic model system, the highest antioxidant activity was observed under low drought stress condition in A. nobilis. MDA and H2O2 content were increased due to both low (75% FC) and moderate (50% FC) drought stress, but they were decreased under severe stress condition (25% FC). Furthermore, A. millefolium revealed the lowest H2O2 (4.96 nm/g FW) and MDA content (176.32 MUmol/g). Investigation of the relationship among different metabolites showed a strong positive correlation with TPC and TFC. Finally, the moderate drought stress treatment (50% FC) was introduced as the optimum condition to obtain appreciable TPC and TFC,, while the highest antioxidant activity was obtained in severe stress condition (25%FC). PMID- 26541162 TI - Selection of Nucleic Acid Aptamers Specific for Mycobacterium tuberculosis. AB - Tuberculosis (TB) remains to be a major global health problem, with about 9 million new cases and 1.4 million deaths in 2011. For the control of tuberculosis as well as other infectious diseases, WHO recommended "ASSURED" (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to the end user) diagnostic tools that can easily be maintained and used in developing countries. Aptamers are promising tools for developing point of-care diagnostic assays for TB. In this study, ssDNA aptamers that recognize Mycobacterium tuberculosis H37Ra were selected by systematic evolution of ligands by exponential enrichment (SELEX). For this purpose, two different selection protocols, ultrafiltration and centrifugation, were applied. A total of 21 TB specific aptamers were selected. These aptamers exhibited "G-rich" regions on the 3' terminus of the aptamers, including a motif of "TGGGG," "GTGG," or "CTGG." Binding capability of selected aptamers were investigated by quantitative PCR and Mtb36 DNA aptamer was found the most specific aptamer to M. tuberculosis H37Ra. The dissociation constant (K d) of Mtb36 aptamer was calculated as 5.09 +/- 1.43 nM in 95% confidence interval. Relative binding ratio of Mtb36 aptamer to M. tuberculosis H37Ra over Mycobacterium bovis and Escherichia coli was also determined about 4 times and 70 times more, respectively. Mtb36 aptamer is highly selective for M. tuberculosis, and it can be used in an aptamer-based biosensor for the detection of M. tuberculosis. PMID- 26541163 TI - Potential Application of Biohydrogen Production Liquid Waste as Phosphate Solubilizing Agent-A Study Using Soybean Plants. AB - With CO2 free emission and a gravimetric energy density higher than gasoline, diesel, biodiesel, and bioethanol, biohydrogen is a promising green renewable energy carrier. During fermentative hydrogen production, 60-70 % of the feedstock is converted to different by-products, dominated by organic acids. In the present investigation, a simple approach for value addition of hydrogen production liquid waste (HPLW) containing these compounds has been demonstrated. In soil, organic acids produced by phosphate solubilizing bacteria chelate the cations of insoluble inorganic phosphates (e.g., Ca3 (PO4)2) and make the phosphorus available to the plants. Organic acid-rich HPLW, therefore, has been evaluated as soil phosphate solubilizer. Application of HPLW as soil phosphate solubilizer was found to improve the phosphorus uptake of soybean plants by 2.18- to 2.74-folds. Additionally, 33-100 % increase in seed germination rate was also observed. Therefore, HPLW has the potential to be an alternative for phosphate solubilizing biofertilizers available in the market. Moreover, the strategy can be useful for phytoremediation of phosphorus-rich soil. PMID- 26541164 TI - An Applicator Delivery System for Fixed-Combination Calcipotriene Plus Betamethasone Dipropionate Topical Suspension (Gel): Innovating Psoriasis Vulgaris Treatment Through Patient Collaboration. AB - : Treatment non-adherence is a complex problem encountered in all therapy areas, particularly in chronic diseases such as psoriasis vulgaris. To address adherence issues, focus is turning towards developing interventions tailored to individual patient needs. Topical therapies remain the mainstay of psoriasis treatment; however, these are associated with additional challenges where preparations may be perceived as messy, inconvenient and time-consuming. Once-daily fixed combination calcipotriene 0.005% (Cal) and betamethasone dipropionate 0.064% (BD) topical suspension is a convenient and effective first-line topical psoriasis therapy. To improve the patient experience with this treatment, we undertook a program-in collaboration with patients and healthcare professionals-to develop a topical treatment delivery system that further caters to the unmet needs of psoriasis patients. The finalized Applicator comprises: an easy to operate pump action lever providing consistently accurate dose delivery (0.05 g of Cal/BD topical suspension/pump); a single-tip nozzle allowing for targeted, precise application to body and scalp psoriasis plaques; two spreading surfaces designed to disperse treatment evenly across both large and small affected skin areas; and a protective cover. Patients listed the following as key Applicator attributes: ease of use, 'less messy' treatment, precise application, consistent accurate dosing, 'no touch' treatment, reduction of wasted treatment and extended length of reach for awkward areas. Although these attributes were well received by most patients and healthcare professionals, some patients did not perceive them all as improvements over their current treatment; this highlights the need to tailor treatment for each individual patient's requirements. For patients who prefer using the Applicator, it has the potential to provide greater control over their daily psoriasis management by providing a simple, convenient treatment option, with minimal impact on their lives. The Applicator may represent a more acceptable treatment delivery system for some patients with psoriasis vulgaris and may, therefore, promote long-term treatment adherence. FUNDING: LEO Pharma. PMID- 26541165 TI - Expression, Crystallization and Preliminary X-ray Diffraction Analyses of Med ORF10 in the Biosynthetic Pathway of an Antitumor Antibiotic Medermycin. AB - Medermycin, as a prominent member of benzoisochromanequinones, possesses strong antitumor activity and is biosynthesized under the control of a 29-ORF-containing biosynthetic gene cluster. Most of ORFs in this gene cluster have not been characterized, including a small protein encoding gene med-ORF10, proposed to play a regulatory role in biosynthesis of medermycin in an unknown mode. In this study, we reported the expression, protein preparation, crystallization and preliminary X-ray diffraction analyses of Med-ORF10 of the wild type Streptomyces strain. Firstly, we cloned and overexpressed med-ORF10 in Escherichia coli and purified the protein with 98% purity and 3 mg/L yield. Then, we crystallized the protein at concentration of 20 mg/mL in condition 22% PEG 3350, 0.2 M magnesium formate and collected the data at 1.78 A resolution. Finally, we detected the expression of Med-ORF10 in Streptomyces by western blotting. In conclusion, this study confirmed the expression of Med-ORF10 protein in the wild-type strain of Streptomyces AM-7161 and collected the X-ray diffraction data of Med-ORF10 crystal at 1.78 A resolution. These studies provide evidences for the functional Med-ORF10 protein in Streptomyces strains and facilitate our further investigation. PMID- 26541166 TI - Mand Training: An Examination of Response-Class Structure in Three Children With Autism and Severe Language Delays. AB - Our primary purpose in this study was to examine the structure of a response class when new members are acquired through mand training. To do this, we replaced existing mands (e.g., reaching) in three children with autism with two new functionally equivalent mands. Next, we examined their responding under immediate- and delayed-reinforcement conditions. Then, we assessed generalization to novel social partners. We employed a reversal design to examine the effectiveness of mand training and to assess responding under both immediate- and delayed-reinforcement conditions. Our results suggest that all children acquired the new mands and that two of the children emitted these responses as replacements when the social partner did not provide access to the reinforcer contingent on the child's first mand. Generalization data indicate that all three children emitted the new mands and two of the children alternated between the new mands with novel social partners. We discuss the clinical implications and the conceptual significance of teaching multiple replacement mands to children with autism and severe language delays. PMID- 26541168 TI - Contemporary survival of adults with congenital heart disease. AB - BACKGROUND: Survival data that are applicable to the current population of adults with congenital heart disease (CHD) are not available. OBJECTIVES: Using an alternative survival analysis with age as the primary time scale, we assessed the contemporary survival of adult patients with CHD. METHODS: Survival was assessed using prospective data of the national registry of adult patients with CHD of the Netherlands. Survival was stratified by severity and lesion, and compared with a standardised general population. RESULTS: Mean age at inclusion was 37 years, and 49% of the study population was male. During a cumulative prospective follow-up of 90, 270 patient-years in 14, 327 patients, 535 deaths occurred. Median survival was 53.4 (95% CI 49.9 to 60.7), 75.4 (95% CI 72.9 to 79.1) and 84.1 (95% CI 81.9 to 87.0) years for patients with severe, moderate and mild lesions, respectively. Survival of most patients with mild lesions did not differ from the general population, while, as expected, survival of patients with severe and moderate lesions was substantially lower (<0.001). CONCLUSIONS: The present study gives insight in the contemporary survival of adults with CHD. This may aid patient counselling, timing of interventions and future research. PMID- 26541169 TI - The modern epidemiology of heart valve disease. PMID- 26541170 TI - The cost-effectiveness of telestroke in the Pacific Northwest region of the USA. AB - INTRODUCTION: Using real-world data from the Providence Oregon Telestroke Network, we examined the cost-effectiveness of telestroke from both the spoke and hub perspectives by level of financial responsibility for these costs and by patient stroke severity. METHODS: We constructed a decision analytic model using patient-level clinical and financial data from before and after telestroke implementation. Effectiveness was measured as quality-adjusted life years (QALYs) and was combined with cost per patient outcomes to calculate incremental cost effectiveness ratios (ICERs). Outcomes were generated (a) overall; (b) by stroke severity, via the National Institute of Health Stroke Scale (NIHSS) at time of arrival, defined as low (<5), medium (5-14) and high (>15); and (c) by percentage of implementation costs paid by spokes (0%, 50%, 100%). RESULTS: Data for 864 patients, 98 pre- and 766 post-implementation, were used to parameterize our model. From the spoke perspective, telestroke had ICERs of US$1322/QALY, US$25,991/QALY and US$50,687/QALY when responsible for 0%, 50%, and 100% of these costs, respectively. Overall, the ICER ranged from US$22,363/QALY to US$71,703/QALY from the hub perspective. CONCLUSIONS: Our results support previous models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective for the spokes if spokes paid for more than half of implementation costs. PMID- 26541171 TI - The effect of telemedicine on cognitive decline in patients with dementia. AB - Introduction Telemedicine has the advantage of providing medical resources in rural areas, but few studies have been conducted to investigate its efficacy in dementia care, compared to face-to-face care. This study evaluated the effectiveness of telemedicine in relation to cognitive changes in patients with dementia. Methods We evaluated cognitive changes over time, according to care modality, in 188 patients with dementia who were registered at our university based dementia clinic. We followed 98 patients using telemedicine services and 90 patients who attended the dementia clinic in person. Patients in the telemedicine group also visited a public health center located in a rural area about 50 km from the dementia clinic. Results Changes in the mean annualized Mini-Mental State Examination (MMSE) score were not significantly different between the telemedicine group and the face-to-face dementia clinic group ( p = 0.291), with changes of 0.60 and 1.03 points, respectively. However, cognitive decline was significantly lower in the telemedicine group for the less severe initial cognitive performance subgroup than more severe cognitive performance subgroup ( p = 0.049), with changes of 0.62 and 1.59 points, respectively. Higher initial Clinical Dementia Rating (CDR) scores, MMSE scores, and age were found to be independent predictive factors of subsequent cognitive changes, as indicated by mean annualized MMSE scores. Discussion These findings suggest that telemedicine may be a useful alternative to face-to-face clinical visits for management of dementia in patients who are located in rural areas. PMID- 26541173 TI - Gene Acquisitions from Bacteria at the Origins of Major Archaeal Clades Are Vastly Overestimated. AB - In a recent article, Nelson-Sathi et al. (NS) report that the origins of major archaeal lineages (MAL) correspond to massive group-specific gene acquisitions via HGT from bacteria (Nelson-Sathi et al. 2015. Origins of major archaeal clades correspond to gene acquisitions from bacteria. Nature 517(7532):77-80.). If correct, this would have fundamental implications for the process of diversification in microbes. However, a reexamination of these data and results shows that the methodology used by NS systematically inflates the number of genes acquired at the root of each MAL, and incorrectly assumes bacterial origins for these genes. A reanalysis of their data with appropriate phylogenetic models accounting for the dynamics of gene gain and loss between lineages supports the continuous acquisition of genes over long periods in the evolution of Archaea. PMID- 26541172 TI - DNA Editing of LTR Retrotransposons Reveals the Impact of APOBECs on Vertebrate Genomes. AB - Long terminal repeat retrotransposons (LTR) are widespread in vertebrates and their dynamism facilitates genome evolution. However, these endogenous retroviruses (ERVs) must be restricted to maintain genomic stability. The APOBECs, a protein family that can edit C-to-U in DNA, do so by interfering with reverse transcription and hypermutating retrotransposon DNA. In some cases, a retrotransposon may integrate into the genome despite being hypermutated. Such an event introduces a unique sequence into the genome, increasing retrotransposon diversity and the probability of developing new function at the locus of insertion. The prevalence of this phenomenon and its effects on vertebrate genomes are still unclear. In this study, we screened ERV sequences in the genomes of 123 diverse species and identified hundreds of thousands of edited sites in multiple vertebrate lineages, including placental mammals, marsupials, and birds. Numerous edited ERVs carry high mutation loads, some with greater than 350 edited sites, profoundly damaging their open-reading frames. For many of the species studied, this is the first evidence that APOBECs are active players in their innate immune system. Unexpectedly, some birds and especially zebra finch and medium ground-finch (one of Darwin's finches) are exceptionally enriched in DNA editing. We demonstrate that edited retrotransposons may be preferentially retained in active genomic regions, as reflected from their enrichment in genes, exons, promoters, and transcription start sites, thereby raising the probability of their exaptation for novel function. In conclusion, DNA editing of retrotransposons by APOBECs has a substantial role in vertebrate innate immunity and may boost genome evolution. PMID- 26541174 TI - Injectable nanoamorphous calcium phosphate based in situ gel systems for the treatment of periapical lesions. AB - Nonsurgical local treatment of a periapical lesion arising from trauma or bacterial infection is a promising innovative approach. The present study investigated the feasibility of developing injectable amorphous calcium phosphate nanoparticles (ACP NPs) and ACP NPs loaded with an anti-inflammatory drug; ibuprofen (IBU-ACP NPs) in the form of thermoreversible in situ gels to treat periapical lesions with the stimulation of bone formation. NPs were produced by a spray-drying technique. Different formulations of Poloxamer 407 were incorporated with/without the produced NPs to form injectable gels. A drug release study was carried out. A 3 month in vivo test on a dog model also was assessed. Results showed successful incorporation of the drug into the NPs of CP during spray drying. The particles had mean diameters varying from 100 to 200 nm with a narrow distribution. A drug release study demonstrated controlled IBU release from IBU ACP NPs at a pH of 7.4 over 24 h. The gelation temperature of the injectable in situ gels based on Poloxamer 407 was measured to be 30 degrees C. After 3 months of implantation in dogs, the results clearly demonstrated that the inclusion of ACP NPs loaded with IBU showed high degrees of periapical bone healing and cementum layer deposition around the apical root tip. PMID- 26541175 TI - A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children. AB - There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 MUg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance. PMID- 26541176 TI - A comparison of Wharton's jelly and cord blood as a source of mesenchymal stem cells for diabetes cell therapy. AB - AIM: In this study, we investigated the differences between mesenchymal stem cells (MSCs), isolated from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) as sources of diabetes mellitus cell therapy. METHODS: After isolation, both cell types were induced to differentiate into insulin producing cells, then the differentiated cells were assessed genetically and functionally. UCB-MSCs and WJ-MSCs were transplanted in the tail veins of streptozotocin-induced diabetic rats. Blood glucose levels were monitored post-transplantation. RESULTS & CONCLUSION: Wharton's jelly was more homogeneous, can better differentiate into insulin producing cells in vitro and better control hyperglycemia in diabetic rats in vivo, as compared with UCB. These results indicate that WJ-MSCs represent a potential source of cells in the field of diabetes mellitus cell therapy. PMID- 26541177 TI - Simvastatin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy. AB - Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post TBI using the oral route of administration and, as such, it will not be further pursued by OBTT. PMID- 26541178 TI - Elevated risk of early reoperation in total hip replacement during the stage of unit closure: A population-based registry study of total hip and knee replacements in Finland, 1998-2011. AB - BACKGROUND AND PURPOSE: The effects of launch or closure of an entire arthroplasty unit on the first or last patients treated in these units have not been studied. Using a 3-year follow-up, we investigated whether patients who were treated at the launch or closure stage of an arthroplasty unit of a hospital would have a higher risk of reoperation than patients treated in-between at the same units. PATIENTS AND METHODS: From the Finnish Arthroplasty Register, we identified all the units that had performed total joint arthroplasty and the units that were launched or closed in Finland between 1998 and 2011. The risks of reoperation within 3 years for the 41,748 total hip and knee replacements performed due to osteoarthritis in these units were modeled with Cox proportional hazards regression, separately for hip and knee and for the launch and the closure stage. RESULTS: The unadjusted and adjusted hazard ratios (HRs) for total hip and knee replacements performed in the initial stage of activity of the units that were launched were similar to the reoperation risks in patients who were operated in these units after the early stage of activity. The unadjusted and risk-adjusted HRs for early reoperation after total hip replacement (THR) were increased at the closure stage (adjusted HR = 1.8, 95% CI: 1.2-2.8). The reoperation risk at the closure stage after total knee replacement (TKR) was not increased. INTERPRETATION: The results indicate that closure of units performing total hip replacements poses an increased risk of reoperation. Closures need to be managed carefully to prevent the quality from deteriorating when performing the final arthroplasties. PMID- 26541179 TI - High-throughput long noncoding RNA profiling for diagnostic and prognostic markers in cancer: opportunities and challenges. PMID- 26541180 TI - Different type 2 diabetes risk assessments predict dissimilar numbers at 'high risk': a retrospective analysis of diabetes risk-assessment tools. AB - BACKGROUND: Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under reported, however, whether a different risk tool alters the predicted risk of an individual. AIM: This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. DESIGN AND SETTING: Cross sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. METHOD: Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes((r)), Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. RESULTS: Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at 'high risk' followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). CONCLUSION: The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes. PMID- 26541181 TI - Weekend opening in primary care: analysis of the General Practice Patient Survey. AB - BACKGROUND: Seven-day opening in primary care is a key policy for the UK government. However, it is unclear if weekend opening will meet patients' needs or lead to additional demand. AIM: To identify patient groups most likely to use weekend opening in primary care. DESIGN AND SETTING: The General Practice Patient Survey 2014, which sampled from all general practices in England, was used. METHOD: Logistic regression was used to measure the associations between perceived benefit from seeing or speaking to someone at the weekend and age, sex, deprivation, health conditions, functioning, work status, rurality, and quality of life. RESULTS: Out of 881 183 participants who responded to the questionnaire, 712 776 (80.9%) did not report any problems with opening times. Of the 168 407 responders (19.1%) who reported inconvenient opening times, 73.9% stated that Saturday opening, and 35.8% Sunday opening, would make it easier for them to see or speak to someone. Only 2.2% of responders reported that Sunday, but not Saturday, opening would make it easier for them. Younger people, those who work full time, and those who could not get time off work were more likely to report that weekend opening would help. People with Alzheimer's disease, learning difficulties, or problems with walking, washing, or dressing were less likely to report that weekend opening would help. CONCLUSION: Most people do not think they need weekend opening, but it may benefit certain patient groups, such as younger people in full-time work. Sunday opening, in addition to Saturday, is unlikely to improve access. PMID- 26541182 TI - Variations in GP-patient communication by ethnicity, age, and gender: evidence from a national primary care patient survey. AB - BACKGROUND: Doctor-patient communication is a key driver of overall satisfaction with primary care. Patients from minority ethnic backgrounds consistently report more negative experiences of doctor-patient communication. However, it is currently unknown whether these ethnic differences are concentrated in one gender or in particular age groups. AIM: To determine how reported GP-patient communication varies between patients from different ethnic groups, stratified by age and gender. DESIGN AND SETTING: Analysis of data from the English GP Patient Survey from 2012-2013 and 2013-2014, including 1,599,801 responders. METHOD: A composite score was created for doctor-patient communication from five survey items concerned with interpersonal aspects of care. Mixed-effect linear regression models were used to estimate age- and gender-specific differences between white British patients and patients of the same age and gender from each other ethnic group. RESULTS: There was strong evidence (P<0.001 for age by gender by ethnicity three-way interaction term) that the effect of ethnicity on reported GP-patient communication varied by both age and gender. The difference in scores between white British and other responders on doctor-patient communication items was largest for older, female Pakistani and Bangladeshi responders, and for younger responders who described their ethnicity as 'Any other white'. CONCLUSION: The identification of groups with particularly marked differences in experience of GP-patient communication--older, female, Asian patients and younger 'Any other white' patients--underlines the need for a renewed focus on quality of care for these groups. PMID- 26541185 TI - VERIFICATION OF INDICATED SKIN ENTRANCE AIR KERMA FOR CARDIAC X-RAY-GUIDED INTERVENTION USING GAFCHROMIC FILM. AB - The aim of this work was to verify the indicated maximum entrance surface air kerma (ESAK) using a GE Innova IGS 520 imaging system during cardiac interventional procedures. Gafchromic XR RV3 films were used for the patient measurements to monitor the maximum ESAK. The films were scanned and calibrated to measure maximum ESAK. Thermoluminescent dosemeters were used to measure the backscatter factor from an anthropomorphic thorax phantom. The measured backscatter factor, 1.53, was in good agreement with Monte Carlo simulations but higher than the one used by the imaging system, 1.20. The median of the ratio between indicated maximum ESAK and measured maximum ESAK was 0.68. In this work, the indicated maximum ESAK by the imaging system's dose map model underestimates the measured maximum ESAK by 32 %. The threshold ESAK for follow-up procedures for patient with skin dose in excess of 2 Gy will be reduced to 1.4 Gy. PMID- 26541183 TI - Association of GPs' risk attitudes, level of empathy, and burnout status with PSA testing in primary care. AB - BACKGROUND: Rates of prostate specific antigen (PSA) test ordering vary among GPs. AIM: To examine whether GPs' risk attitude, level of empathy, and burnout status are associated with PSA testing. DESIGN AND SETTING: Register and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis. METHOD: PSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs' risk attitudes, empathy, and burnout status from a 2012 survey. RESULTS: Patients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test. CONCLUSION: Various aspects of GPs' risk-taking attitudes were associated with patients' probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing. PMID- 26541184 TI - A 5-year survival analysis of 160 Biomet Magnum M2 metal-on-metal total hip prostheses. AB - BACKGROUND: Large-head metal-on-metal (MoM) total hip arthroplasties (THA) are associated with high failure rates and possible pseudotumour formation. This study reports the first results of 160 Biomet Magnum M2 large-head MoM total hip articulations. PATIENTS AND METHODS: From 2006 to 2010 the Reinier de Graaf Hospital implanted 160 large-head Magnum M2 MoM THAs (Biomet Inc. Warsaw, Indiana, USA) in 150 patients. These patients were recalled after a warning from the Dutch Orthopaedic Association. Patients were offered a clinical and radiographic assessment of the hip prosthesis, serum control on cobalt and chromium ions, and an ultrasound of the hip. If indicated, additional MARS-MRI or CT scan was performed. Descriptive statistical analysis, correlations, t-tests, non-parametric tests and implant survival were calculated. RESULTS: The mean follow-up was 6.1 years (4.8-8.4). A cumulative survival rate of 93.1% (95% CI: 88.3-98%) was found after 5 years. Reasons for revision were loosening, pain, infection and pseudotumour formation. The prevalence of pseudotumour formation around the prostheses was 8.75%. CONCLUSIONS: This study reports the first results of 160 MoM THAs implanted in our clinic from 2006-2010. In total, 13 (8.1%) of the THAs were eligible for revision after the recall. In most patients the reason for revision was pseudotumour formation. A total of 14 (8.75%) pseudotumours were diagnosed at the first recall. These results show that a comprehensive follow-up strategy is essential for MoM THAs to promptly identify and manage early complications. PMID- 26541186 TI - DEVELOPMENT OF SIMULATED WORKPLACE FIELDS AT KRISS FOR PERFORMANCE TEST OF NEUTRON PERSONAL DOSEMETERS. AB - Simulated workplace neutron fields have been developed at the Korea Research Institute of Standards and Science (KRISS). An (241)Am-Be neutron source and a cylindrical moderator composed of stainless steel and heavy water were installed in a 10-cm-thick concrete block with dimensions of 150 * 120 * 120 cm(3) The neutron energy spectrum at a distance of 66.5 cm was measured using a Bonner sphere spectrometer and was found to agree with the spectrum obtained from the Monte Carlo N-Particle Extended simulation to within 5 %. The neutron fluence-to personal dose equivalent conversion coefficients were (20.8-43.6) pSv.cm(2) and were thus in good agreement with those of reactor fields. The results showed that the KRISS-simulated workplace neutron fields can be used for performance tests and the calibration service of neutron personal dosemeters. PMID- 26541187 TI - EXPOSURE OF THE SWISS POPULATION BY RADIODIAGNOSTICS: 2013 REVIEW. AB - In 2013, a nationwide investigation was conducted in Switzerland to establish the population's exposure from medical X rays. A hybrid approach was used combining the Raddose database accessible on-line by the participating practices and the Swiss medical tariffication system for hospitals. This study revealed that the average annual number of examinations is 1.2 per inhabitant, and the associated annual effective dose is 1.4 mSv. It also showed that computed tomography is the most irradiating modality and that it delivers 70 % of the total dose. The annual effective dose per inhabitant registered a 17 % increase in 5 y and is comparable with what was recently reported in neighbouring countries. PMID- 26541188 TI - SECONDARY NEUTRON DOSES IN A PROTON THERAPY CENTRE. AB - The formation of secondary high-energy neutrons in proton therapy can be a concern for radiation protection of staff. In this joint intercomparative study (CERN, SCK*CEN and IBA/IRISIB/ULB), secondary neutron doses were assessed with different detectors in several positions in the Proton Therapy Centre, Essen (Germany). The ambient dose equivalent H(*)(10) was assessed with Berthold LB 6411, WENDI-2, tissue-equivalent proportional counter (TEPC) and Bonner spheres (BS). The personal dose equivalent Hp(10) was measured with two types of active detectors and with bubble detectors. Using spectral and basic angular information, the reference Hp(10) was estimated. Results concerning staff exposure show H(*)(10) doses between 0.5 and 1 nSv/monitoring unit in a technical room. The LB 6411 showed an underestimation of H(*)(10), while WENDI-2 and TEPC showed good agreement with the BS data. A large overestimation for Hp(10) was observed for the active personal dosemeters, while the bubble detectors showed only a slight overestimation. PMID- 26541189 TI - EURADOS-IDEAS GUIDELINES (VERSION 2) FOR THE ESTIMATION OF COMMITTED DOSES FROM INCORPORATION MONITORING DATA. AB - Dose assessment after intakes of radionuclides requires application of biokinetic and dosimetric models and assumptions about factors influencing the final result. In 2006, a document giving guidance for such assessment was published, commonly referred to as the IDEAS Guidelines. Following its publication, a working group within the European networks CONRAD and EURADOS was established to improve and update the IDEAS Guidelines. This work resulted in Version 2 of the IDEAS Guidelines, which was published in 2013 in the form of a EURADOS report. The general structure of the original document was maintained; however, new procedures were included, e.g. the direct dose assessment method for (3)H or special procedure for wound cases applying the NCRP wound model. In addition, information was updated and expanded, e.g. data on dietary excretion of U, Th, Ra and Po for urine and faeces or typical and achievable values for detection limits for different bioassay measurement techniques. PMID- 26541190 TI - Spontaneous closure of traumatic tympanic membrane perforations: observational study. PMID- 26541191 TI - Discovery of serum proteomic biomarkers for prediction of response to moxibustion treatment in rats with collagen-induced arthritis: an exploratory analysis. AB - OBJECTIVE: To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. RESULTS: Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. CONCLUSIONS: Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets. PMID- 26541192 TI - Correction. PMID- 26541193 TI - Correction. PMID- 26541194 TI - The modernisation of acupuncture. PMID- 26541195 TI - The Cooperative Health Research in South Tyrol (CHRIS) study: rationale, objectives, and preliminary results. AB - The Cooperative Health Research In South Tyrol (CHRIS) study is a population based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment. PMID- 26541196 TI - Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to investigate the risk of common cancers in Chinese patients with T2DM. METHODS: A population-based retrospective cohort study including 36,379 T2DM patients was conducted in Minhang District of Shanghai, China, during 2004 to 2010. All T2DM patients were enrolled from the standardized management system based on local electronic information system. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. Standardized incidence ratios (SIR) and 95% confidence interval (CI) were used to estimate the risk of cancers among T2DM patients. RESULTS: Overall crude incidence rate (CIR) of cancers was 955.21 per 105 person-years in men and 829.57 per 105 person-years in women. Increased risk of cancer was found in both gender, with an SIR being 1.28 (95% CI = 1.17-1.38) in men and 1.44 (95% CI =1.32-1.55) in women. Increased risk of colon (SIR = 1.97; 95% CI = 1.49 to 2.46), rectum (1.72; 1.23 to 2.21), prostate (2.87; 2.19 to 3.56), and bladder cancers (1.98, 1.28 to 2.68) were observed in men and elevated risk of colon (1.67; 1.25 to 2.08), breast (1.66; 1.38 to 1.95), and corpus uteri cancers (2.87; 2.03 to 3.71) were observed in women. CONCLUSIONS: Our results indicate that Chinese patients with T2DM may have an increased risk of some cancers, and the increase may vary by sub-sites of cancers. PMID- 26541197 TI - Evaluation of leishmanicidal activity and cytotoxicity of Ricinus communis and Azadirachta indica extracts from western Kenya: in vitro and in vivo assays. AB - BACKGROUND: Despite advances to targeted leishmanicidal chemotherapy, defies around severe toxicity, recent emergence of resistant variants and absence of rational vaccine still persist. This necessitates search and/or progressive validation of accessible medicinal remedies including plant based. The study examined both in vivo and in vitro response of L. major infection to combined therapy of Ricinus communis and Azadirachta indica extracts in BALB/c mice as the mouse model. A comparative study design was applied. RESULTS: BALB/c mice, treated with combination therapy resulted in significantly (p < 0.05) larger reduction of lesion than those treated with monotherapies. The spleno-somatic index was found to be significantly low with combination therapy than monotherapies. Antiparasitic effect of A. indica and R. communis on amastigote with a 50 % inhibitory concentration (IC50) was of 11.5 and 16.5 ug mL(-1) respectively while combination therapy gave 9.0 ug ml(-1) compared to the standard drugs, Pentostam and amphotericin B which had an IC50 of 6.5 and 4.5 ug ml(-1) respectively. Optimal efficacy of A. indica and R. communis was 72 and 59.5 % respectively, combination therapy gave 88 %, while Pentostam and amphotericin B had 98 and 92 % respectively against amastigotes. Against promastigotes A. indica and R. Communis gave an IC50 of 10.1, 25.5 ug mL(-1) respectively, while combination, 12.2 ug mL(-1) against 4.1 and 5.0 ug ml(-1) for Pentostam and amphotericin B respectively. The optimal efficacy of the compounds against promastigotes was 78.0, 61.5 and 91.2 % (A. indica, R. communis and A. indica + R. communis respectively) against 96.5 and 98 % for Pentostam and amphotericin B respectively. The concentrations at optimal efficacy were significantly different (p < 0.05) among the test compounds. An evaluation of the IC50 values of the combination therapies clearly reveals synergistic effects. CONCLUSION: Combination therapy of A. indica and R. communis had best antileishmanial activity than the monotherapies. The active ingredients of both R. communis and A. indica need to be fractionated, and studied further for activity against Leishmania parasites. PMID- 26541198 TI - Pseudoaneurysm of graft-graft anastomosis of a hand-sewn branched graft: a case report. AB - BACKGROUND: Pseudoaneurysm of graft-graft anastomosis is an extremely rare but potentially fatal complication after thoracic aorta replacement with a prosthetic graft. We report a case of pseudoaneurysm at the graft-graft anastomosis of a hand-sewn branched graft. CASE PRESENTATION: A 65-year-old man underwent total arch replacement with a hand-sewn branched graft for Stanford type A acute aortic dissection 22 years ago. During follow-up, serial CT scans showed a pseudoaneurysm on the branched graft which warranted reintervention. Surgical repair involved direct suture of multiple bleeding points which were found at the sites of the hand-sewn branches anastomosis. The postoperative course was uneventful, and no signs of bleeding were observed by CT after the reoperation. CONCLUSIONS: Long-term follow-up is essential to detect late complications at the site of hand-sewn anastomosis. PMID- 26541199 TI - Disparities in hypertension among black Caribbean populations: a scoping review by the U.S. Caribbean Alliance for Health Disparities Research Group (USCAHDR). AB - BACKGROUND: Despite the large body of research on racial/ethnic disparities in health, there are limited data on health disparities in Caribbean-origin populations. This scoping review aimed to analyze and synthesize published and unpublished literature on the disparities in hypertension and its complications among Afro-Caribbean populations. METHODS: A comprehensive protocol, including a thorough search strategy, was developed and used to identify potentially relevant studies. Identified studies were then screened for eligibility using pre specified inclusion/exclusion criteria. An extraction form was developed to chart data and collate study characteristics including methods and main findings. Charted information was tagged by disparity indicators and thematic analysis performed. Disparity indicators evaluated include ethnicity, sex, socioeconomic status, disability, sexual orientation and geographic location. Gaps in the literature were identified and extrapolated into a gap map. RESULTS: A total of 455 hypertension related records, published between 1972 and 2012, were identified and screened. Twenty-one studies met inclusion criteria for detailed analysis. The majority of studies were conducted in the United Kingdom and utilized a cross-sectional study design. Overall, studies reported a higher prevalence of hypertension among Caribbean blacks compared to West African blacks and Caucasians. Hypertension and its related complications were highest in persons with low socioeconomic status. Gap analysis showed limited research data reporting hypertension incidence by sex and socioeconomic status. No literature was found on disability status or sexual orientation as it relates to hypertension. Prevalence and morbidity were the most frequently reported outcomes. CONCLUSION: The literature on hypertension health disparities in Caribbean origin populations is limited. Future research should address these knowledge gaps and develop approaches to reduce them. PMID- 26541201 TI - Narrowing the gap: from semiconductor to semimetal in the homologous series of rare-earth zinc arsenides RE(2-y)Zn4As4.n(REAs) and Mn-substituted derivatives RE(2-y)Mn(x)Zn(4-x)As4.n(REAs) (RE = La-Nd, Sm, Gd). AB - A homologous series of ternary rare-earth zinc arsenides, prepared by reactions of the elements at 750 degrees C, has been identified with the formula RE(2 y)Zn4As4.n(REAs) (n = 2, 3, 4) for various RE members. They adopt trigonal structures: RE(4-y)Zn4As6 (RE = La-Nd), space group R3m1, Z = 3; RE(5-y)Zn4As7 (RE = Pr, Nd, Sm, Gd), space group P3m1, Z = 1; RE(6-y)Zn4As8 (RE = La-Nd, Sm, Gd), space group R3m1, Z = 3. The Zn atoms can be partially substituted by Mn atoms, resulting in quaternary derivatives RE(2-y)Mn(x)Zn(4-x)As4.n(REAs). Single crystal structures were determined for nine ternary and quaternary arsenides RE(2 y)M4As4.n(REAs) (M = Mn, Zn) as representative examples of these series. The structures are built by stacking close-packed nets of As atoms, sometimes in very long sequences, with RE atoms occupying octahedral sites and M atoms occupying tetrahedral sites, resulting in an intergrowth of [REAs] and [M2As2] slabs. The recurring feature of all members of the homologous series is a sandwich of [M2As2]-[REAs]-[M2As2] slabs, while rocksalt-type blocks of [REAs] increase in thickness between these sandwiches with higher n. Similar to the previously known related homologous series REM(2-x)As2.n(REAs) which is deficient in M, this new series RE(2-y)M4As4.n(REAs) exhibits deficiencies in RE to reduce the electron excess that would be present in the fully stoichiometric formulas. Enthalpic and entropic factors are considered to account for the differences in site deficiencies in these two homologous series. Band structure calculations indicate that the semiconducting behaviour of the parent n = 0 member (with CaAl2Si2-type structure) gradually evolves, through a narrowing of the gap between valence and conduction bands, to semimetallic behaviour as the number of [REAs] blocks increases, to the limit of n = infinity for rocksalt-type REAs. PMID- 26541202 TI - Facile multi-dimensional profiling of chemical gradients at the millimetre scale. AB - A vast number of conventional physicochemical methods are suitable for the analysis of homogeneous samples. However, in various cases, the samples exhibit intrinsic heterogeneity. Tomography allows one to record approximate distributions of chemical species in the three-dimensional space. Here we develop a simple optical tomography system which enables performing scans of non homogeneous samples at different wavelengths. It takes advantage of inexpensive open-source electronics and simple algorithms. The analysed samples are illuminated by a miniature LCD/LED screen which emits light at three wavelengths (598, 547 and 455 nm, corresponding to the R, G, and B channels, respectively). On presentation of every wavelength, the sample vial is rotated by ~180 degrees , and videoed at 30 frames per s. The RGB values of pixels in the obtained digital snapshots are subsequently collated, and processed to produce sinograms. Following the inverse Radon transform, approximate quasi-three-dimensional images are reconstructed for each wavelength. Sample components with distinct visible light absorption spectra (myoglobin, methylene blue) can be resolved. The system was used to follow dynamic changes in non-homogeneous samples in real time, to visualize binary mixtures, to reconstruct reaction-diffusion fronts formed during the reduction of 2,6-dichlorophenolindophenol by ascorbic acid, and to visualize the distribution of fungal mycelium grown in a semi-solid medium. PMID- 26541200 TI - Complete haplotype phasing of the MHC and KIR loci with targeted HaploSeq. AB - BACKGROUND: The MHC and KIR loci are clinically relevant regions of the genome. Typing the sequence of these loci has a wide range of applications including organ transplantation, drug discovery, pharmacogenomics and furthering fundamental research in immune genetics. Rapid advances in biochemical and next generation sequencing (NGS) technologies have enabled several strategies for precise genotyping and phasing of candidate HLA alleles. Nonetheless, as typing of candidate HLA alleles alone reveals limited aspects of the genetics of MHC region, it is insufficient for the comprehensive utility of the aforementioned applications. For this reason, we believe phasing the entire MHC and KIR locus onto a single locus-spanning haplotype can be a critical improvement for better understanding transplantation biology. RESULTS: Generating long-range (>1 Mb) phase information is traditionally very challenging. As proximity-ligation based methods of DNA sequencing preserves chromosome-span phase information, we have utilized this principle to demonstrate its utility towards generating full-length phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants (coding and non-coding) within these two loci that collectively span 4-megabases. CONCLUSIONS: By haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease. PMID- 26541203 TI - Graphene-based room-temperature implementation of a modified Deutsch-Jozsa quantum algorithm. AB - We present an implementation of a one-qubit and two-qubit modified Deutsch-Jozsa quantum algorithm based on graphene ballistic devices working at room temperature. The modified Deutsch-Jozsa algorithm decides whether a function, equivalent to the effect of an energy potential distribution on the wave function of ballistic charge carriers, is constant or not, without measuring the output wave function. The function need not be Boolean. Simulations confirm that the algorithm works properly, opening the way toward quantum computing at room temperature based on the same clean-room technologies as those used for fabrication of very-large-scale integrated circuits. PMID- 26541204 TI - Out of body, out of space: Impaired reference frame processing in eating disorders. AB - A distorted body representation is a core symptom in eating disorders (EDs), though its mechanism is unclear. Allocentric lock theory, emphasising the role of reference frame processing in body image, suggests that ED patients may be (b)locked to an (allocentric) representation of their own body stored in long term memory (e.g., my body is fat) that is not updated (modified) by the (real time egocentric) perception-driven experience of the physical body. Employing a well-validated virtual reality-based procedure, relative to healthy controls, ED patients showed deficits in the ability to refer to and update a long-term stored (allocentric) representation with (egocentric) perceptual-driven inputs. PMID- 26541205 TI - Healing disturbance with suture bridge configuration repair in rabbit rotator cuff tear. AB - BACKGROUND: Medial row failure has been reported in the suture bridge technique of rotator cuff repair. This study compared the healing response of suture bridge configuration repair (SBCR) and parallel type transosseous repair (PTR). METHODS: Acute rotator cuff repair was performed in 32 rabbits. Both shoulders were repaired using PTR or SBCR. In PTR, simple PTR was performed through 2 parallel transosseous tunnels created using a microdrill. In SBCR, 2 additional crisscross transosseous tunnels were added to mimic arthroscopic SBCR. At 1, 2, and 5 weeks postoperatively, comparative biomechanical testing was performed in 8 rabbits, and histologic analysis, including immunohistochemical staining for CD31, was performed in 4 rabbits. RESULTS: Failure loads at 1 week (38.12 +/- 20.43 N vs 52.00 +/- 27.23 N; P = .284) and 5 weeks (97.93 +/- 48.35 N vs 119.60 +/- 60.81 N; P = .218) were not statistically different between the SBCR and PTR groups, respectively, but were significantly lower in the SBCR group than in the PTR group (23.56 +/- 13.56 N vs. 44.25 +/- 12.53 N; P = .009), respectively, at 2 weeks. Markedly greater fibrinoid deposition was observed in the SBCR group than in the PTR group at 2 weeks. For vascularization, there was a tendency that more vessels could be observed in PTR than in SBCR at 2 weeks (15.9 vs 5.6, P = .068). CONCLUSIONS: In a rabbit acute rotator cuff repair model, SBCR exhibited inferior mechanical strength, and fewer blood vessels were observed at the healing site at 2 weeks postoperatively. Medial row tendon failure was more common in SBCR. Surgeons should consider the clinical effect of SBCR when performing rotator cuff repair. PMID- 26541206 TI - Evaluation of the coracoid and coracoacromial arch geometry on Thiel-embalmed cadavers using the three-dimensional MicroScribe digitizer. AB - BACKGROUND: Understanding the geometry of the coracoid and coracoacromial arch will improve surgical intervention in shoulder surgery. METHODS: Thirty pairs of scapulae from 20 female and 10 male deceased donors, average age of 82 years (range, 62-101 years), were scanned and measurements taken using the 3 dimensional (3D) MicroScribe digitizer (Immersion Corp, San Jose CA, USA) and Rhino software (McNeel North America, Seattle, WA, USA). RESULTS: The following mean angles were determined: coracoid slope, 44 degrees +/- 11 degrees ; coracoid deviation, 35 degrees +/- 6 degrees ; coracoid root to glenoid, 115 degrees +/- 14 degrees ; coracoid head to glenoid, 110 degrees +/- 11 degrees ; scapular spine angle, 35 degrees +/- 6 degrees ; and coracoacromial angle, 63 degrees +/- 9 degrees . The following mean distances were also determined: coracoid height, 10 +/- 3 mm; coracoacromial distance, 42 +/- 7 mm; coracoacromial arch height, 20 +/- 5 mm; and coracoid (anterior, 29 +/- 6 mm; middle, 20 +/- 4 mm; posterior tip, 18 +/- 6 mm) to the glenoid fossa. The coracoid root-to-glenoid angle was significantly correlated with the coracoacromial angle. In addition, coracoid slope was significantly correlated with coracoid root-to-glenoid angle and also with coracoid deviation. Left shoulders had a significantly higher coracoid-to-glenoid angle (P < .029) than right shoulders. Women had a significantly higher coracoid root-to-glenoid angle than men (P < .042), and men had a significantly higher coracoid deviation (P < .011), anterior (P < .006) and posterior coracoid-to-glenoid distances (P < .03), and coracoacromial arch height (P < .07) than women. CONCLUSIONS: This is the first time that the 3D MicroScribe digitizer has been used to evaluate the geometry of the coracoacromial arch and coracoid process. PMID- 26541207 TI - Cardiotoxicity in rabbits after long-term nandrolone decanoate administration. AB - Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period. PMID- 26541208 TI - Metabolic profile of mephedrone: Identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites. AB - Metabolic profile of mephedrone (4-methylmethcathinone, 4-MMC), a frequently abused recreational drug, was determined in rats in vivo. The urine of rats dosed with a subcutaneous bolus dose of 20mg 4-MMC/kg was analysed by LC/MS. Ten phase I and five phase II metabolites were identified by comparison of their retention times and MS(2) spectra with those of authentic reference standards and/or with the MS(2) spectra of previously identified metabolites. The main metabolic pathway was N-demethylation leading to normephedrone (4-methylcathinone, 4-MC) which was further conjugated with succinic, glutaric and adipic acid. Other phase I metabolic pathways included oxidation of the 4-methyl group, carbonyl reduction leading to dihydro-metabolites and omega-oxidation at the position 3'. Five of the metabolites detected, namely, 4-carboxynormephedrone (4-carboxycathinone, 4 CC), 4-carboxydihydronormephedrone (4-carboxynorephedrine, 4-CNE), hydroxytolyldihydro-normephedrone (4-hydroxymethylnorephedrine, 4-OH-MNE) and conjugates of 4-MC with glutaric and adipic acid, have not been reported as yet. The last two conjugates represent a novel, hitherto unexploited, type of phase II metabolites in mammals together with an analogous succinic acid conjugate of 4-MC identified by Pozo et al. (2015). These conjugates might be potentially of great importance in the metabolism of other psychoactive amines. PMID- 26541210 TI - [Dental management in patients with cirrhosis]. AB - The present article makes a brief review about dental management of the patients with cirrhosis. It focus on problems related with infections, haemorrhagic events and treatment with drugs of common use in odontology. PMID- 26541209 TI - Dental demineralization, radiation caries and oral microbiota in patients with head and neck cancer. PMID- 26541211 TI - High prevalence of Trypanosoma vegrandis in bats from Western Australia. AB - The present study describes the first report of Trypanosoma vegrandis in bats using morphology and sequence analysis of the 18S rRNA gene. The PCR prevalence of T. vegrandis in bats was 81.8% (18/22). The high prevalence of T. vegrandis in the present study suggests that bats may play an important role in the epidemiology of T. vegrandis in Australia. T. vegrandis appears to be geographically dispersed, has a wide distribution in Australia and low levels of host specificity. PMID- 26541212 TI - Biodegradable DNA-enabled poly(ethylene glycol) hydrogels prepared by copper-free click chemistry. AB - Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne functionalized multi-arm poly(ethylene glycol) with azide-functionalized single stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA cross-linked hydrogels upon exposure to the model endonucleases Benzonase((r)) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems. PMID- 26541213 TI - Cholangitis due to afferent loop obstruction after cephalic duodenopancreatectomy. PMID- 26541214 TI - The L-type voltage-dependent calcium channel long-term potentiation is higher in the dorsal compared with the ventral associational/commissural CA3 hippocampal synapses. AB - The diversification between dorsal (DH) and ventral (VH) hippocampus includes the different ability to support NMDA receptor-dependent long-term synaptic potentiation (LTP). In this study, we assessed the ability of associational/commissural connections in the CA3 hippocampal field to show NMDA receptor-independent LTP. We found that high-frequency stimulation under blockade of NMDA receptors induced greater LTP in DH (40.7+/-8.5%) than in VH (17.1+/ 4.6%). The blocker of L-type voltage-dependent calcium channels (VDCC) nifedipine prevented the induction of LTP. We hypothesize that the different ability for VDCC-LTP between DH and VH might have important implications in the memory related information processing performed by the circuits of the two hippocampal segments. PMID- 26541215 TI - Assessment of femur geometrical parameters using EOSTM imaging technology in patients with atypical femur fractures; preliminary results. AB - Atypical femur fractures (AFF) arise in the subtrochanteric and diaphyseal regions. Because of this unique distribution, we hypothesized that patients with AFF demonstrate specific geometrical variations of their lower limb whereby baseline tensile forces applied to the lateral cortex are higher and might favor the appearance of these rare stress fractures, when exposed to bisphosphonates. Using the low irradiation 2D-3D X-ray scanner EOSTM imaging technology we aimed to characterize and compare femur geometric parameters between women who sustained bisphosphonate-associated AFF and those who had experienced similar duration of exposure to bisphosphonates but did not sustain fractures. Conditional logistic regression models were constructed to estimate the association between selected geometric parameters and the occurrence of AFF. We identified 16 Caucasian women with AFF and recruited 16 ethnicity-, sex-, age-, height- and cumulative bisphosphonate exposure-matched controls from local osteoporosis clinics. Compared to controls, those with AFF had more lateral femur bowing (-3.2 degrees SD [3.4] versus -0.8 degrees SD [1.9] p=0.02). In regression analysis, lateral femur bowing was associated with the risk of AFF (aOR 1.54; 95% CI 1.04-2.28, p=0.03). Women who sustained a subtrochanteric AFF demonstrated a lesser femoral neck shaft angle (varus geometry) than those with a fracture at a diaphyseal site (121.9 [3.6] degrees versus 127.6 [7.2] degrees , p=0.07), whereas femur bowing was more prominent in those with a diaphyseal fracture compared to those with a subtrochanteric fracture (-4.3 [3.2] degrees versus -0.9 [2.7] degrees , p=0.07). Our analyses support that subjects with AFF exhibit femoral geometry parameters that result in higher tensile mechanical load on the lateral femur. This may play a critical role in the pathogenesis of AFF and requires further evaluation in a larger size population. PMID- 26541216 TI - Layer-by-Layer Assembled C/S Cathode with Trace Binder for Li-S Battery Application. AB - The C/S cathode with only 0.5 wt % binder, composed with Nafion and PVP, was assembled layer-by-layer for lithium-sulfur battery (Li-S) application. It achieved excellent binding strength and battery performance compared to the cathode with 10 wt % PVDF, which is promising to further increase the practical energy density of Li-S batteries. PMID- 26541217 TI - Mini-fluid challenge can predict arterial pressure response to volume expansion in spontaneously breathing patients under spinal anaesthesia. AB - INTRODUCTION: The objective of this study was to test whether stroke volume (SV) variations in response to a fixed mini-fluid challenge (DeltaSV100) measured by impedance cardiography (ICG) could predict an increase in arterial pressure with volume expansion in spontaneously breathing patients under spinal anaesthesia. METHODS: Thirty-four patients, monitored by ICG who required intravenous fluid to expand their circulating volume during surgery under spinal anaesthesia, were studied. Haemodynamic variables and bioimpedance indices (blood pressure, SV, cardiac output [CO]) were measured before and after fluid challenge with 100mL of crystalloid, and before/after volume expansion. Responders were defined by >=15% increase in systolic arterial pressure (SAP) after infusion of 500 mL of crystalloid solution. RESULTS: SAP increased by >=15% in 20 (59%) of the 34 patients. SAP, SV, and CO increased and HR decreased only in responders. SV variations in response to mini-fluid challenge and volume expansion differed between patients who showed arterial responsiveness and those in whom SAP did not increase with volume expansion (11.6% [9.1-19.3] versus 2.5% [1.3-7], P<0.001, and 22.4% [11.7-36.6] versus 0.9 [0-5.5], P<0.001, respectively). DeltaSV100 predicted an increase of arterial pressure with an area under the receiver operating characteristic (AUC) curve of 0.89 (CI95%: 0.73-0.97, P<0.001). The cut off was 5%. Baseline SAP and HR were not predictive of arterial responsiveness (P>0.05). CONCLUSION: A DeltaSV100 over 5% accurately predicted arterial pressure response to volume expansion during surgery. PMID- 26541218 TI - Ketamine for pain management in France, an observational survey. AB - CONTEXT: Before updating the French guidelines on postoperative pain treatment in 2015, the Pain Committee of the French Society of Anaesthesiology and Intensive Care (SFAR) conducted a survey on the medical use of ketamine in France. METHODS: An online questionnaire was nationally distributed to members of SFAR, the French Pain Society (SFETD) and the French Society of Emergency Medicine (SFMU). The questionnaire included questions on demographic data, the type of patients for whom ketamine was prescribed, the doses used, the side effects and safety measures associated with the administration of ketamine. RESULTS: A total of 1388 questionnaires were analysed. Ninety-two percent of the responders declared that they used ketamine. Ketamine was widely used as anti-hyperalgesic medication but the modalities of administration and the doses varied greatly and were not in accordance with the guidelines. Despite the lack of evidence and guidelines, ketamine has also been used to treat acute and chronic pain. Doses, duration and localization of the patients during administration have varied greatly. Psychedelic effects and hallucinations are the most feared side effects. In terms of monitoring during ketamine infusion, 15% of physicians declared that no monitoring was necessary while 59%, 55%, 59% and 77% monitored heart rate, SpO2, blood pressure and level of consciousness, respectively. CONCLUSION: Anaesthesiologists have integrated the benefit of ketamine in preventing hyperalgesia but there is no consensus on doses and duration. For other indications (acute and chronic pain treatment), toxicity and the absence of significant benefit call for guidelines from scientific societies. PMID- 26541219 TI - Fluid resuscitation in Ebola Virus Disease: A comparison of peripheral and central venous accesses. AB - INTRODUCTION: Ebola Virus Disease (EVD) causes severe diarrhoea and vomiting, leading to dehydration and electrolyte abnormalities. Treatment remains supportive and often requires intravenous (IV) access. IV catheters are difficult to insert and maintain in this context. Our primary objective was to compare peripheral venous catheters (PVCs) and central venous catheters (CVCs) for volume resuscitation in patients with EVD. MATERIAL AND METHODS: We performed a prospective observational study between January and March 2015 at the Conakry Healthcare Workers Ebola Treatment Unit (ETU). The primary judgement criterion was the ratio of the daily infused volume of fluids to the prescribed volume (DIV/PV). RESULTS: Fourteen patients were admitted. Twenty-eight PVCs and 8 CVCs were inserted. CVCs had a longer survival time (96 +/- 34 hours versus 33.5 +/- 21 hours, P<0.001). The mean DIV/PV was higher for the CVCs (0.95+/-0.08 versus 0.7 +/- 0.27, P<0.001), as well as the number of days with full administration of prescribed IV fluids (71.2% versus 34.1%, P=0.002). DISCUSSION: Inserting CVCs is a safe and reliable way of obtaining IV access in ETUs, provided adequately trained personnel are available. CVCs optimize fluid infusion compared to PVCs. Further studies comparing fluid management strategies in EVD are necessary. PMID- 26541220 TI - Contemporary Surgical Indications and Referral Trends in Revision Total Hip Arthroplasty: A 10-Year Review. AB - BACKGROUND: Revision total hip arthroplasty (THA) represents nearly 15% of all hip arthroplasty procedures in the United States and is projected to increase. The purpose of our study was to summarize the contemporary indications for revision THA surgery at a tertiary referral medical center. We also sought to identify the indications for early and late revision surgery and define the prevalence of outside institution referral for revision THA. METHODS: Using our institution's arthroplasty registry, we identified a retrospective cohort of 870 consecutive patients who underwent revision THA at our hospital from 2004 to 2014. Records were reviewed to collect data on patient's primary and revision THA procedures, and the interval between primary THA and revision surgery was determined. RESULTS: Aseptic loosening (31.3%), osteolysis (21.8%), and instability (21.4%) were the overall most common indications for revision THA and the most common indications for revision surgery within 5 years of primary THA. Aseptic loosening and osteolysis were the most common indications for revision greater than 5 years from primary THA. Only 16.4% of revised hips had their index arthroplasty performed at our hospital, whereas 83.6% were referred to our institution. CONCLUSIONS: Aseptic loosening, osteolysis, and instability remain the most common contemporary indications for revision THA in an era of alternative bearings and modular components. Most of our revisions were referred from outside institutions, which highlights the transfer of a large portion of the revision THA burden to tertiary referral centers, a pattern that could be exacerbated under future bundled payment models. PMID- 26541221 TI - Reply. PMID- 26541222 TI - Reply. PMID- 26541223 TI - Perils of the new labor management guidelines: Should we stop asking "when" to act on delayed progression and start asking "why" the cervical dilatation is slower than the expected labor curve? PMID- 26541224 TI - From molecules in space to molecules in breath. AB - The evolution of the selected ion flow tube, SIFT, used to study ion-molecule reactions of interstellar significance, to the selected ion flow tube mass spectrometry, SIFT-MS, analytical technique is described briefly. Focus is placed on the application of SIFT-MS to breath analysis and its potential for the detection of volatile biomarkers of disease including respiratory pathogens. Typical concentrations of particular volatile breath biomarkers are given and their associations with specific diseases are indicated. A special case is the identification and quantification of gaseous hydrogen cyanide that is elevated in the exhaled breath of patients with cystic fibrosis and is now taken as a biomarker of Pseudomonas aeruginosa infection of the airways. PMID- 26541225 TI - MicroRNA-340 Mediates Metabolic Shift in Oral Squamous Cell Carcinoma by Targeting Glucose Transporter-1. AB - PURPOSE: MicroRNA-340 (miR-340) is deregulated in many human cancers in correlation with tumor progression. Recent studies have found that microRNAs play key roles in energy metabolism. This study explored the contributions of miR-340 to the metabolic shift in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: MiR-340 expression was measured by real-time polymerase chain reaction. MiR-340 mimics, miR-340 inhibitor, and scramble small interfering RNA were transfected into SAS human tongue SCC cells to observe their effects on cell proliferation, colony formation, lactate secretion, and glucose uptake rate. Moreover, the relation between the level of miR-340 and glucose transporter-1 (Glut1) was investigated. RESULTS: The expression of miR-340 was decreased and thus induced a metabolic switch in oral cancer cells. The decrease in miR-340 increased Glut1 expression, leading to an increase in lactate secretion and glucose uptake rate. The altered metabolism induced by miR-340 resulted in the rapid proliferation of oral cancer cells. CONCLUSION: The findings suggest that miR-340 might act as a molecular switch that contributes to the regulation of glycolysis in OSCC by regulating Glut1 expression. PMID- 26541226 TI - A Case of a Methicillin-Resistant Staphylococcus Aureus Retropharyngeal Abscess With Mediastinal Extension in an 11-Month-Old Girl. AB - We present the case of an 11-month-old girl with Mycoplasma pneumoniae-associated pneumonia who was subsequently diagnosed with a methicillin-resistant Staphylococcus aureus retropharyngeal abscess with mediastinal extension. PMID- 26541227 TI - Predictability of Prevention of Hypoxia by Nasal High-flow System in Dental Procedures. PMID- 26541228 TI - The HIV-1 Entry Process: A Stoichiometric View. AB - HIV-1 infection starts with fusion of the viral and the host cell membranes, a process mediated by the HIV-1 envelope glycoprotein trimer. The number of trimers required to complete membrane fusion, referred to as HIV-1 entry stoichiometry, remains under debate. A precise definition of HIV-1 entry stoichiometry is important as it reflects the efficacy of the viral entry process and steers the infectivity of HIV-1 virion populations. Initial estimates suggested a unanimous entry stoichiometry across HIV-1 strains while recent findings showed that HIV-1 strains can differ in entry stoichiometry. Here, we review current analyses of HIV-1 entry stoichiometry and point out future research directions to further define the interplay between entry stoichiometry, virus entry fitness, transmission, and susceptibility to antibody neutralization. PMID- 26541229 TI - Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis. AB - AIMS: Scutellaria discolor Colebr. has been extensively used in traditional medicine against several diseases. The purpose of this study was to investigate the anticancer potential of S. discolor and to isolate the bioactive principle responsible for the anticancer activity. METHODS: Cytotoxicity experiments were performed on cancer and normal cells using MTT assay. The mechanism of cell death was evaluated using real time PCR array, fluorescence microscopy, flow cytometry and Western blotting. MTT assay guided isolation (partition and column chromatography) was performed to identify the antiproliferative principle. Quantification of the active principle was done using HPLC. KEY FINDINGS: Acetone extract of S. discolor (SDE) inhibited the growth and survival of cancer cells to varying degree, but the inhibition was found to be maximum in cervical cancer cell lines. There was no significant toxicity induced to normal cells. The cell death was mediated through apoptosis. There was increased mitochondrial membrane depolarization, expression of Bax, caspase-9, caspase-3 and cleaved-PARP indicating that SDE-induced caspase dependent apoptosis in HeLa cells. Moreover, SDE caused cell cycle arrest in G2 phase in HeLa cells. Cytotoxicity guided fractionation of SDE led to the isolation of chrysin as the active principle responsible for the antiproliferative activity for cervical cancer cells. Interestingly, chrysin was the major phytochemical constituent present in S. discolor. SIGNIFICANCE: S. discolor is an important anticancer plant and a new source of chrysin. PMID- 26541230 TI - Risk factors for intraoperative calcar fracture in cementless total hip arthroplasty. AB - BACKGROUND AND PURPOSE: Intraoperative periprosthetic femoral fracture is a known complication of cementless total hip arthroplasty (THA). We determined the incidence of--and risk factors for--intraoperative calcar fracture, and assessed its influence on the risk of revision. PATIENTS AND METHODS: This retrospective analysis included 3,207 cementless THAs (in 2,913 patients). 118 intraoperative calcar fractures were observed in these hips (3.7%). A control group of 118 patients/hips without calcar fractures was randomly selected. The mean follow-up was 4.2 (1.8-8.0) years. Demographic data, surgical data, type of implant, and proximal femur morphology were evaluated to determine risk factors for intraoperative calcar fracture. RESULTS: The revision rates in the calcar fracture group and the control group were 10% (95% CI: 5.9-17) and 3.4% (CI: 1.3 8.4), respectively. The revision rate directly related to intraoperative calcar fracture was 7.6%. The Hardinge approach and lower age were risk factors for calcar fracture. In the fracture group, 55 of 118 patients (47%) had at least one risk factor, while only 23 of118 patients in the control group (20%) had a risk factor (p = 0.001). Radiological analysis showed that in the calcar fracture group, there were more deviated femoral anatomies and proximal femur bone cortices were thinner. INTERPRETATION: Intraoperative calcar fracture increased the risk of revision. The Hardinge approach and lower age were risk factors for intraoperative calcar fracture. To avoid intraoperative fractures, special attention should be paid when cementless stems are used with deviant-shaped proximal femurs and with thin cortices. PMID- 26541231 TI - Effects of sound amplification in self-perception of tinnitus and hearing loss in the elderly. AB - OBJECTIVE: To determine the effect of the use of hearing aids in self-perception of tinnitus and hearing loss in the elderly. METHODS: A total of 24 elderly patients between 60 and 70 years of age with moderate-grade sensorineural hearing loss were evaluated and divided into two groups according to the presence or absence of tinnitus. All volunteers were fitted with binaural micro-channel hearing aids of the same brand and model and submitted to tests, scales, and questionnaires relevant to this topic. The evaluations were performed before and after one and three months of effective use of these hearing aids. RESULTS: Acoustic stimulation through the effective use of hearing aids caused a reduction in the perception of tinnitus sound intensity (especially in evaluations with the prosthesis on) and in nuisance associated with this symptom and with hearing loss. In addition, all participants were satisfied with the use of hearing aids. CONCLUSION: The continuous use of hearing aids is beneficial for the treatment of tinnitus and hearing loss, bringing satisfaction to users. PMID- 26541232 TI - Effectiveness of sound therapy in patients with tinnitus resistant to previous treatments: importance of adjustments. AB - INTRODUCTION: The difficulty in choosing the appropriate therapy for chronic tinnitus relates to the variable impact on the quality of life of affected patients and, thus, requires individualization of treatment. OBJECTIVE: To evaluate the effectiveness of using sound generators with individual adjustments to relieve tinnitus in patients unresponsive to previous treatments. METHODS: A prospective study of 10 patients with chronic tinnitus who were unresponsive to previous drug treatments, five males and five females, with ages ranging from 41 to 78 years. Bilateral sound generators (Reach 62 or Mind 9 models) were used daily for at least 6h during 18 months. The patients were evaluated at the beginning, after 1 month and at each 3 months until 18 months through acuphenometry, minimum masking level, the Tinnitus Handicap Inventory, visual analog scale, and the Hospital Anxiety and Depression Scale. The sound generators were adjusted at each visit. RESULTS: There was a reduction of Tinnitus Handicap Inventory in nine patients using a protocol with a customized approach, independent of psychoacoustic characteristics of tinnitus. The best response to treatment occurred in those with whistle-type tinnitus. A correlation among the adjustments and tinnitus loudness and minimum masking level was found. Only one patient, who had indication of depression by Hospital Anxiety and Depression Scale, did not respond to sound therapy. CONCLUSION: There was improvement in quality of life (Tinnitus Handicap Inventory), with good response to sound therapy using customized settings in patients who did not respond to previous treatments for tinnitus. PMID- 26541233 TI - Bilateral oropharyngeal hairy polyps: a rare cause of dyspnea in newborns. PMID- 26541234 TI - First branchial cleft fistula: a difficult challenge. PMID- 26541236 TI - Ultrathin SnSe2 Flakes Grown by Chemical Vapor Deposition for High-Performance Photodetectors. AB - High-quality ultrathin single-crystalline SnSe2 flakes are synthesized under atmospheric-pressure chemical vapor deposition for the first time. A high performance photodetector based on the individual SnSe2 flake demonstrates a high photoresponsivity of 1.1 * 10(3) A W(-1), a high EQE of 2.61 * 10(5)%, and superb detectivity of 1.01 * 10(10) Jones, combined with fast rise and decay times of 14.5 and 8.1 ms, respectively. PMID- 26541235 TI - Nasal reconstruction in Binder syndrome. PMID- 26541237 TI - A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice. AB - BACKGROUND: Trimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral MU- and kappa-opioid receptors has been evaluated as a treatment in a limited number of patients undergoing sedation-free full colonoscopy. The efficiency of such treatment was comparable to sedation-based colonoscopies to relieve from pain and discomfort. METHODS: A new and improved trimebutine salt capable of releasing in vivo hydrogen sulphide (H2S), a gaseous mediator known to reduce nociception, has been developed. This drug salt (GIC 1001) is composed of trimebutine bearing a H2S-releasing counterion (3 thiocarbamoylbenzoate, 3TCB), the latter having the ability to release H2S. GIC 1001 has been tested here in a mouse model of colorectal distension. RESULTS: In mice, while orally given trimebutine (the maleate salt, non-H2 S-releaser) only slightly reduced the nociceptive response to increasing pressures of colorectal distension, oral administration of GIC-1001 (the H2S-releaser) was able to significantly reduce nociceptive response to all noxious stimuli, in a dose dependent manner. This effect of GIC-1001 was significantly better than the effects of its parent compound trimebutine administered at equimolar doses. CONCLUSIONS: Taken together, these results demonstrated increased antinociceptive properties for GIC-1001 compared to trimebutine, suggesting that this compound would be a better option to relieve from visceral pain and discomfort induced by lumenal distension. PMID- 26541238 TI - Utility of combining morphological characters, nuclear and mitochondrial genes: An attempt to resolve the conflicts of species identification for ciliated protists. AB - Ciliates comprise a highly diverse protozoan lineage inhabiting all biotopes and playing crucial roles in regulating microbial food webs. Nevertheless, subtle morphological differences and tiny sizes hinder proper species identification for many ciliates. Here, we use the species-rich taxon Frontonia and employ both nuclear and mitochondrial loci. We attempt to assess the level of genetic diversity and evaluate the potential of each marker in delineating species of Frontonia. Morphological features and ecological characteristics are also integrated into genetic results, in an attempt to resolve conflicts of species identification based on morphological and molecular methods. Our studies reveal: (1) the mitochondrial cox1 gene, nuclear ITS1 and ITS2 as well as the hypervariable D2 region of LSU rDNA are promising candidates for species delineation; (2) the cox1 gene provides the best resolution for analyses below the species level; (3) the V2 and V4 hypervariable regions of SSU rDNA, and D1 of LSU rDNA as well as the 5.8S rDNA gene do not show distinct barcoding gap due to overlap between intra- and inter-specific genetic divergences; (4) morphological character-based analysis shows promise for delimitation of Frontonia species; and (5) all gene markers and character-based analyses demonstrate that the genus Frontonia consists of three groups and monophyly of the genus Frontonia is questionable. PMID- 26541239 TI - Historical biogeography of Reticulitermes termites (Isoptera: Rhinotermitidae) inferred from analyses of mitochondrial and nuclear loci. AB - Termites of the genus Reticulitermes are ecologically and economically important wood-feeding social insects that are widespread in the Holarctic region. Despite their importance, no study has yet attempted to reconstruct a global time-scaled phylogeny of Reticulitermes termites. In this study, we sequenced mitochondrial (2096bp) and nuclear (829bp) loci from 61 Reticulitermes specimens, collected across the genus' entire range, and one specimen of Coptotermes formosanus, which served as an outgroup. Bayesian and Maximum likelihood analyses conducted on the mitochondrial and nuclear sequences support the existence of four main lineages that span four global geographical regions: North America (NA lineage), western Europe (WE lineage), a region including eastern Europe and western Asia (EA+WA lineage), and eastern Asia (EA lineage). The mitochondrial data allowed us to clarify the phylogenetic relationships among these lineages. They were also used to infer a chronogram that was time scaled based on age estimates for termite fossils (including the oldest Reticulitermes fossils, which date back to the late Eocene-early Oligocene). Our results support the hypothesis that the extant Reticulitermes lineage first differentiated in North America. The first divergence event in the ancestral lineage of Reticulitermes occurred in the early Miocene and separated the Nearctic lineages (i.e., the NA lineages) from the Palearctic lineages (i.e., WE, EE+WA, and EA lineages). Our analyses revealed that the main lineages of Reticulitermes diversified because of vicariance and migration events, which were probably induced by major paleogeographic and paleoclimatic changes that occurred during the Cenozoic era. This is the first global and comprehensive phylogenetic study of Reticulitermes termites, and it provides a crucial foundation for studying the evolution of phenotypic and life history traits in Reticulitermes. For instance, the phylogeny we obtained suggested that 'asexual queen succession', a unique reproductive system, independently evolved at least three times during the diversification of the genus. PMID- 26541240 TI - Molecular phylogeny of the Neotropical fish genus Tetragonopterus (Teleostei: Characiformes: Characidae). AB - Tetragonopterinae encompasses characid species of the genus Tetragonopterus, which are widely distributed throughout east of the Andes in South America. While taxonomy has recently clarified the species diversity and molecular evidence strongly supports the monophyly of Tetragonopterus, no interspecific relationship studies are currently available. Here we used a large molecular dataset composed of two mitochondrial and three nuclear loci containing an extensive taxon sampling within the family Characidae and included eleven species of Tetragonopterus to generate the first time-calibrated phylogeny for Tetragonopterinae. Our results support monophyly of the subfamily represented solely by Tetragonopterus and corroborate previous molecular hypothesis of close relationship with Exodon plus Roeboexodon and the subfamily Characinae. Internally, we found Moenkhausia georgiae as sister species to all remaining species followed by T. rarus, being both species endemic to the Guiana Shield drainages. Species-level relationships are first hypothesized and putative morphological apomorphies are discussed as support to monophyletic clades. Our time-calibrated phylogeny suggested an origin of the genus during the Late Oligocene-Early Miocene. We hypothesized that the Andean geological activity followed by transformations in the Amazonian hydrographic scenario during the Miocene may have promoted most of the lineage diversification within the Tetragonopterus. PMID- 26541241 TI - Sleep-stage sequencing of sleep-onset REM periods in MSLT predicts treatment response in patients with narcolepsy. AB - Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 +/- 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2. PMID- 26541242 TI - Targeting melanoma: unusual epigenetics reveals the dynamic rewiring of metastatic cells. PMID- 26541243 TI - Control strategies against Campylobacter at the poultry production level: biosecurity measures, feed additives and vaccination. AB - Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union, and ranks second in the United States only behind salmonellosis. In Europe, there are about nine million cases of campylobacteriosis every year, making the disease a major public health issue. Human cases are mainly caused by the zoonotic pathogen Campylobacter jejuni. The main source of contamination is handling or consumption of poultry meat. Poultry constitutes the main reservoir of Campylobacter, substantial quantities of which are found in the intestines following rapid, intense colonization. Reducing Campylobacter levels in the poultry chain would decrease the incidence of human campylobacteriosis. As primary production is a crucial step in Campylobacter poultry contamination, controlling the infection at this level could impact the following links along the food chain (slaughter, retail and consumption). This review describes the control strategies implemented during the past few decades in primary poultry production, including the most recent studies. In fact, the implementation of biosecurity and hygiene measures is described, as well as the immune strategy with passive immunization and vaccination trials and the nutritional strategy with the administration of organic and fatty acids, essential oil and plant-derived compound, probiotics, bacteriocins and bacteriophages. PMID- 26541244 TI - Systematic review of psychological and social outcomes of adolescents undergoing bariatric surgery, and predictors of success. AB - The psychological and social outcomes of bariatric surgery in adolescents, together with psychological and social predictors of success, were systematically reviewed. PubMed, EMBASE, ISI Web of Science and PsychInfo were searched on July 2014. Existing data were sparse; 15 were suitable for qualitative review and six for meta-analysis (four quality of life [QOL], two depression). One study was a randomized controlled trial. A total of 139 subjects underwent Roux-en-Y gastric bypass, 202 underwent adjustable gastric band and 64 underwent sleeve gastrectomy. Overall QOL improved after bariatric surgery, regardless of surgical type with peak improvement at 6-12 months. Meta-analysis of four studies showed changed in overall QOL at latest follow-up of 2.80 standard deviation (SD) (95% confidence interval [CI] 1.23-4.37). Depression improved across all studies, regardless of procedure (effect size -0.47 SD [95% CI -0.76, -0.18] at 4-6 months). Two cohorts reported changes in both overall QOL and depression following a quadratic trajectory, with overall improvement over 2 years and deterioration in the second post-operative year. There were limited data on other psychological and social outcomes. There were insufficient data on psychosocial predictors of outcome to form evidence-based recommendations for patient selection for bariatric surgery at this time. PMID- 26541245 TI - The role of residence time in diagnostic models of global carbon storage capacity: model decomposition based on a traceable scheme. AB - As a key factor that determines carbon storage capacity, residence time (tauE) is not well constrained in terrestrial biosphere models. This factor is recognized as an important source of model uncertainty. In this study, to understand how tauE influences terrestrial carbon storage prediction in diagnostic models, we introduced a model decomposition scheme in the Boreal Ecosystem Productivity Simulator (BEPS) and then compared it with a prognostic model. The result showed that tauE ranged from 32.7 to 158.2 years. The baseline residence time (tau'E) was stable for each biome, ranging from 12 to 53.7 years for forest biomes and 4.2 to 5.3 years for non-forest biomes. The spatiotemporal variations in tauE were mainly determined by the environmental scalar (xi). By comparing models, we found that the BEPS uses a more detailed pool construction but rougher parameterization for carbon allocation and decomposition. With respect to xi comparison, the global difference in the temperature scalar (xit) averaged 0.045, whereas the moisture scalar (xiw) had a much larger variation, with an average of 0.312. We propose that further evaluations and improvements in tau'E and xiw predictions are essential to reduce the uncertainties in predicting carbon storage by the BEPS and similar diagnostic models. PMID- 26541246 TI - Tick-borne encephalitis in a child with previous history of completed primary vaccination. AB - We report the case of a 13-year-old girl who presented with fever, headache, nausea and pain behind the right ear. Cerebrospinal fluid (CSF; leukocytes 227/MUL), electroencephalogram and cerebral magnetic resonance imaging were indicative of meningoencephalitis. Despite intensive therapy the general condition worsened and the patient was admitted to the intensive care unit. Serological analysis of CSF and serum indicated acute tick-borne encephalitis virus (TBEV) infection (IgG and IgM positive). TBEV infection has been reported after incomplete and complete vaccination. TBEV vaccination breakthrough in childhood has been shown to cause severe disease. It has been suggested that immunized patients develop more severe disease due to altered immune response, but the exact mechanism is unknown. In the presence of typical symptoms and a history of vaccination, possible vaccination breakthrough or missing booster vaccination should be considered. PMID- 26541247 TI - Discrepancies between in-home interviews and electronic medical records on regularly used drugs among home care clients. AB - PURPOSE: To compare discrepancies between in-home interviews and electronic medical records (EMRs) on regularly used prescription drugs among older home care clients. METHODS: The participants were home care clients aged 75 years or older living in three Finnish municipalities. In-home interview data on regular prescription drug use from 276 home care clients were compared with EMRs. Agreement between the in-home interview data and EMRs was assessed using Cohen's kappa. RESULTS: A majority (83%, n = 229) of the home care clients had discrepancies between in-home interview data and EMRs, and 40% had discrepancies that could clinically compromise their treatment. Living with a spouse or other family member, use of private health care services, diagnosed asthma/COPD or excessive polypharmacy was associated with having discrepancies. Discrepancies were more common among clients with better functioning and ability to self-manage drug use. Agreement between in-home interview data and EMRs was very good or good for other drug groups, but moderate for opioids, paracetamol, benzodiazepines and benzodiazepine-related drugs and lubricant eye drops, and poor for selective beta 2-adrenoceptor agonists. The most common clinically important discrepancies were psychotropics, opioids and agents acting on the renin-angiotensin system and beta blocking agents. CONCLUSIONS: Eight out of ten home care clients had discrepancies between in-home interview data and EMRs. Of these discrepancies, 40% were clinically important. PMID- 26541248 TI - Leukemia Inhibitory Factor Haplodeficiency Desynchronizes Glial Reactivity and Exacerbates Damage and Functional Deficits after a Concussive Brain Injury. AB - Reactions of both astrocytes and microglia to central nervous system injury can be beneficial or detrimental to recovery. To gain insights into the functional importance of gliosis, we developed a new model of adolescent closed-head injury (CHI) and interrogated the behavioral, physiological, and cellular outcomes after a concussive CHI in leukemia inhibitory factor (LIF) haplodeficient mice. These mice were chosen because LIF is important for astrocyte and microglial activation. Behaviorally, the LIF haplodeficient animals were equally impaired 4 h after the injury, but in the subsequent 2 weeks, the LIF haplodeficient mice acquired more severe motor and sensory deficits, compared with wild type mice. The prolonged accumulation of neurological impairment was accompanied by desynchronization of the gliotic response, increased cell death, axonal degeneration, diminished callosal compound action potential, and hypomyelination. Our results clearly show that LIF is an essential injury-induced cytokine that is required to prevent the propagation of secondary neurodegeneration. PMID- 26541249 TI - Vaccine Hesitancy. AB - Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. PMID- 26541250 TI - 35-Year-Old Man With Thrombocytopenia and Generalized Lymphadenopathy. PMID- 26541251 TI - Hodgkin Lymphoma: Diagnosis and Treatment. AB - Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents. PMID- 26541252 TI - In reply--Association of Social Support Source and Size of Social Support Network With All-Cause Mortality in a National Prospective Cohort. PMID- 26541253 TI - Association of Social Support Source and Size of Social Support Network With All Cause Mortality in a National Prospective Cohort. PMID- 26541254 TI - Risk of Disseminated Varicella Zoster in Immunosuppressed Patients Receiving Zoster Vaccination. PMID- 26541255 TI - In reply--Risk of Disseminated Varicella Zoster in Immunosuppressed Patients Receiving Zoster Vaccination. PMID- 26541256 TI - New Oral Anticoagulants in Elderly Adults With Chronic Kidney Disease. PMID- 26541257 TI - In reply--New Oral Anticoagulants in Elderly Adults With Chronic Kidney Disease. PMID- 26541258 TI - Extramedullary Hematopoiesis in beta-Thalassemia. PMID- 26541259 TI - 39-Year-Old Woman With Headache and Fever. PMID- 26541262 TI - Robust method for the analysis of phytochelatins in rice by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry based on polymeric column materials. AB - A sensitive and robust high-performance liquid chromatography coupled with electrospray tandem mass spectrometry method for the identification and quantification of glutathione and phytochelatins from rice was developed. Homogenized samples were extracted with water containing 100 mM dithiothreitol, and solid-phase extraction using polymer anion exchange resin was employed for sample purification. Chromatography was performed on a polymeric column with acetonitrile and water containing 0.1% formic acid as the mobile phase at the flow rate of 300 MUL/min. The limit of quantitation was 6-100 nM. This assay showed excellent linearity for both glutathione and phytochelatins over physiological normal ranges, with correlation coefficients (r) > 0.9976. Recoveries for four biothiols were within the range of 76-118%, within relative standard deviations less than 15%. The intraday precision (n = 7) was 2.1-13.3%, and the interday precision over 15 days was 4.3-15.2%. The optimized method was applied to analyze tissue samples from rice grown using nutrient solutions with three different cadmium concentrations (0, 50, and 100 MUM). With increasing cadmium concentrations, the content of phytochelatin 2 and phytochelatin 3 in rice roots increased, in contrast to most phytochelatins, and the content of glutathione in rice stems and roots decreased significantly. PMID- 26541261 TI - Breathing air to save energy--new insights into the ecophysiological role of high affinity [NiFe]-hydrogenase in Streptomyces avermitilis. AB - The Streptomyces avermitilis genome encodes a putative high-affinity [NiFe] hydrogenase conferring the ability to oxidize tropospheric H2 in mature spores. Here, we used a combination of transcriptomic and mutagenesis approaches to shed light on the potential ecophysiological role of the enzyme. First, S. avermitilis was either exposed to low or hydrogenase-saturating levels of H2 to investigate the impact of H2 on spore transcriptome. In total, 1293 genes were differentially expressed, with 1127 and 166 showing lower and higher expression under elevated H2 concentration, respectively. High H2 exposure lowered the expression of the Sec protein secretion pathway and ATP-binding cassette-transporters, with increased expression of genes encoding proteins directing carbon metabolism toward sugar anabolism and lower expression of NADH dehydrogenase in the respiratory chain. Overall, the expression of relA responsible for the synthesis of the pleiotropic alarmone ppGpp decreased upon elevated H2 exposure, which likely explained the reduced expression of antibiotic synthesis and stress response genes. Finally, deletion of hhySL genes resulted in a loss of H2 uptake activity and a dramatic loss of viability in spores. We propose that H2 is restricted to support the seed bank of Streptomyces under a unique survival mixotrophic energy mode and discuss important ecological implications of this finding. PMID- 26541263 TI - Serum dipeptidyl peptidase-4 is associated with multiple vertebral fractures in type 2 diabetes mellitus. AB - OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture although they have slightly higher bone mineral density (BMD). There is no evidence that dipeptidyl peptidase-4 (DPP-4) is involved in the bone fragility of the patients. The aim of this study was to investigate the association between serum DPP-4 levels and vertebral fractures (VFs) in men with T2DM. DESIGN: We conducted a cross-sectional study and investigated the relationships between serum DPP-4 levels vs BMD at lumbar spine, femoral neck and radius, bone turnover markers and presence of VFs in 204 Japanese male patients. RESULTS: Multiple regression analyses adjusted for confounders such as age, duration of diabetes, body mass index, serum creatinine, HbA1c, serum albumin, log(alanine transaminase), and log(C-reactive protein) showed that serum DPP-4 was positively associated with bone formation markers (bone-specific alkaline phosphatase and osteocalcin) as well as a bone resorption marker [tartrate-resistant acid phosphatase 5b (TRACP-5b)] (beta = 0.25, P < 0.01; beta = 0.17, P < 0.05; and beta = 0.30, P < 0.01, respectively), but not BMD at each site. Multivariate logistic regression analyses adjusted for the confounders described above revealed that serum DPP-4 levels were associated with the presence of multiple VFs (odds ratio 1.61, 95% confidential interval 1.05-2.49 per SD increase, P < 0.05). This association was still significant after additional adjustment for any sites of BMD or bone turnover markers except for TRACP-5b. CONCLUSIONS: We firstly showed that high level of serum DPP-4 is associated with prevalent multiple VFs independently of BMD and bone formation in men with T2DM. PMID- 26541264 TI - Age- and Sex-Related Differences in Efficacy With an Angiotensin II Receptor Blocker and a Calcium Channel Blocker in Asian Hypertensive Patients. AB - Overseas guidelines to manage hypertension recommend selecting different drugs depending on age, but no studies have investigated the relationship between drug selection and age- and sex-related differences, although such information may help to reduce the risk of cardiovascular mortality. The Azilsartan Circadian and Sleep Pressure--the First Study (ACS1) trial was a multicentered, randomized, open-label, two-parallel group study comparing the effects of an angiotensin II receptor blocker (azilsartan) and a calcium channel blocker (amlodipine). The present study is a post hoc analysis of ACS1 to investigate age- and sex-related differences in the antihypertensive effects between azilsartan and amlodipine. Azilsartan significantly reduced diastolic blood pressure in male patients younger than 60 years compared with amlodipine, but amlodipine significantly reduced systolic blood pressure in female patients 60 years and older compared with azilsartan. A randomized controlled trial to evaluate cardiovascular outcomes will demonstrate whether a diastolic blood pressure-lowering effect with azilsartan is significantly effective in male patients younger than 60 years. PMID- 26541265 TI - Protection of soil carbon within macro-aggregates depends on intra-aggregate pore characteristics. AB - Soil contains almost twice as much carbon (C) as the atmosphere and 5-15% of soil C is stored in a form of particulate organic matter (POM). Particulate organic matter C is regarded as one of the most labile components of the soil C, such that can be easily lost under right environmental settings. Conceptually, micro environmental conditions are understood to be responsible for protection of soil C. However, quantitative knowledge of the specific mechanisms driving micro environmental effects is still lacking. Here we combined CO2 respiration measurements of intact soil samples with X-ray computed micro-tomography imaging and investigated how micro-environmental conditions, represented by soil pores, influence decomposition of POM. We found that atmosphere-connected soil pores influenced soil C's, and especially POM's, decomposition. In presence of such pores losses in POM were 3-15 times higher than in their absence. Moreover, we demonstrated the presence of a feed-forward relationship between soil C decomposition and pore connections that enhance it. Since soil hydrology and soil pores are likely to be affected by future climate changes, our findings indicate that not-accounting for the influence of soil pores can add another sizable source of uncertainty to estimates of future soil C losses. PMID- 26541266 TI - A comparative genomics and reductive dehalogenase gene transcription study of two chloroethene-respiring bacteria, Dehalococcoides mccartyi strains MB and 11a. AB - Genomes of two trichloroethene (TCE)-respiring Dehalococcoides (Dhc) mccartyi, strains MB and 11a, were sequenced to identify reductive dehalogenases (RDase) responsible for oraganohalide respiration. Transcription analyses were conducted to verify the roles of RDase subunit A genes (rdhA) in chloroethene respiration. Some interesting features of the strain MB draft genome include a large genome size, two CRISPR-cas type I systems, and 38 rdhA genes. Strain 11a has a stream lined genome with 11 rdhA genes, of which nine are distinct. Quantitative real time PCR transcription analysis of RDase gene transcripts showed that a single RDase gene, designated mbrA, was up-regulated upon exposure to TCE and no other RDase genes were considerably expressed in strain MB. A single RDase gene, designated vcrA, was up-regulated upon exposure to TCE and expressed at a steady level until all chloroethenes were completely dechlorinated to ethene at 147 h in strain 11a. Overall, this study reports the genomes of two distinct Dhc strains; both contain numerous uncharacterized RDase genes, but in each strain only one such gene was expressed highly during organohalide respiration. PMID- 26541267 TI - Metal-Free Intermolecular Azide-Alkyne Cycloaddition Promoted by Glycerol. AB - Metal-free intermolecular Huisgen cycloadditions using nonactivated internal alkynes have been successfully performed in neat glycerol, both under thermal and microwave dielectric heating. In sharp contrast, no reaction occurs in other protic solvents, such as water, ethanol, or diols. DFT calculations have shown that the BnN3/glycerol adduct promotes a more important stabilization of the corresponding LUMO than that produced in the analogous BnN3/alcohol adducts, favoring the reactivity with the alkyne in the first case. The presence of copper salts in the medium did not change the reaction pathway (Cu(I) acts as spectator), except for disubstituted silylalkynes, for which desilylation takes place in contrast to the metal-free system. PMID- 26541268 TI - Mycobacterium tuberculosis Inhibits RAB7 Recruitment to Selectively Modulate Autophagy Flux in Macrophages. AB - Here we report a novel regulatory mechanism for autophagy-mediated degradation of Mycobacterium tuberculosis (Mtb) and specific strategy exploited by the virulent Mtb to evade it. We show while both avirulent (H37Ra) and virulent (H37Rv) mycobacteria could readily localize to autophagosomes, their maturation into autolysosomes (flux) was significantly inhibited by the latter strain. The inhibition of autophagy flux by the virulent strain was highly selective, as it did not perturb the basal autophagy flux in the macrophages. Selective inhibition of flux of Mtb-containing autophagosomes required virulence regulators PhoP and ESAT-6. We show that the maturation of Mtb-containing autophagosomes into autolysosomes required recruitment of the late endosome marker RAB7, forming the intermediate compartment amphisomes. Virulent Mtb selectively evaded their targeting to the amphisomes. Thus we report a crosstalk between autophagy and phagosome maturation pathway and highlight the adaptability of Mtb, manifested by selective regulation of autophagy flux. PMID- 26541269 TI - Variations in physiological and biochemical traits of oak seedlings grown under drought and ozone stress. AB - Despite the huge biodiversity characterizing the Mediterranean environment, environmental constraints, such as high sunlight and high temperatures alongside with dry periods, make plant survival hard. In addition, high irradiance leads to increasing ozone (O3 ) concentrations in ambient air. In this era of global warming, it is necessary to understand the mechanisms that allow native species to tolerate these environmental constraints and how such mechanisms interact. Three Mediterranean oak species (Quercus ilex, Quercus pubescens and Quercus cerris) with different features (drought tolerant, evergreen or deciduous species) were selected to assess their biometrical, physiological and biochemical responses under drought and/or O3 stress (80-100 nl l(-1) of O3 for 5 h day(-1) for 77 consecutive days). Leaf visible injury appeared only under drought stress (alone or combined with O3 ) in all three species. Drought * O3 induced strong reductions in leaf dry weight in Q. pubescens and Q. cerris (-70 and -75%, respectively). Alterations in physiological (i.e. decrease in maximum carboxylation rate) and biochemical parameters (i.e. increase in proline content and build-up of malondialdehyde by-products) occurred in all the three species, although drought represented the major determinant. Quercus ilex and Q. pubescens, which co-occur in dry environments, were more tolerant to drought and drought * O3 . Quercus ilex was the species in which oxidative stress occurred only when drought was applied with O3 . High plasticity at a biochemical level (i.e. proline content) and evergreen habitus are likely on the basis of the higher tolerance of Q. ilex. PMID- 26541270 TI - Analysis of acutely exacerbated chronic tinnitus by the Tinnitus Handicap Inventory. AB - OBJECTIVE: To examine factors potentially contributing to acutely exacerbated chronic tinnitus initiation using the Tinnitus Handicap Inventory. METHODS: Sixty acutely exacerbated chronic tinnitus out-patients were divided into two groups depending on whether hearing loss was aggravated or stable during tinnitus exacerbation. Total Tinnitus Handicap Inventory scores and scores for the three subscales (assessing functional limitations, emotional attitudes and catastrophic thoughts) were analysed. RESULTS: Total Tinnitus Handicap Inventory scores did not differ between groups. In patients with acutely exacerbated chronic tinnitus and aggravated hearing loss, functional subscale scores were significantly higher after acutely exacerbated chronic tinnitus than at baseline, but catastrophic and emotional subscale scores did not change. In patients with acutely exacerbated chronic tinnitus and stable hearing loss, emotional subscale scores were significantly higher after acutely exacerbated chronic tinnitus than at baseline, but catastrophic and functional subscale scores did not change. CONCLUSION: Elevated Tinnitus Handicap Inventory functional subscale scores might indicate further hearing loss, whereas elevated emotional subscale scores might be associated with negative life or work events. PMID- 26541271 TI - Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case-control study assessing long-term quality of life. AB - Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in achalasia patients using a population-based case-control method, and to assess HRQL between treatment interventions. Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115) using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores for SF-12 (Mental Component Summary score [MCS 12] and Physical Component Summary score [PCS-12]) and ASQ were compared between cases and controls, or between intervention groups, using an independent t-test. Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were treated with a Heller's myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4-11.5). Comparing achalasia patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However, both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL between patients treated with Heller's myotomy, pneumatic dilatation or both treatment modalities. In summary, despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one treatment over another. PMID- 26541273 TI - Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients. AB - Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus >=70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications. PMID- 26541274 TI - p16 staining has limited value in predicting the outcome of histological low grade squamous intraepithelial lesions of the cervix. AB - In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n=507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of high-grade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (P<0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2 3.1; P=0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re evaluation (HR: 1.6; 95% CI: 0.9-2.6; P=0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1. PMID- 26541272 TI - Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. AB - MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis. In this study, we determined MYC rearrangement status (n=344) and Myc expression (n=535) in a well characterized DLBCL cohort, individually assessed the clinical and pathobiological features of patients with MYC rearrangement and Myc protein overexpression, and analyzed the prognosis and gene expression profiling signatures associated with these MYC abnormalities in germinal center B-cell-like and activated B-cell-like DLBCL. Our results showed that the prognostic importance of MYC rearrangement vs Myc overexpression is significantly different in germinal center B-cell-like vs activated B-cell-like DLBCL. In germinal center B-cell-like DLBCL, MYC-rearranged germinal center B-cell-like DLBCL patients with Myc overexpression significantly contributed to the clinical, biological, and prognostic characteristics of the overall Myc-overexpressing germinal center B cell-like DLBCL group. In contrast, in activated B-cell-like DLBCL, the occurrence, clinical and biological features, and prognosis of Myc overexpression were independent of MYC rearrangement. High Myc levels and Myc-independent mechanisms, either tumor cell intrinsic or related to tumor microenvironment, conferred significantly worse survival to MYC-rearranged germinal center B-cell like DLBCL patients, even among Myc(high)Bcl-2(high) DLBCL patients. This study provides new insight into the tumor biology and prognostic effects associated with MYC dysregulation and suggest that detection of both MYC translocations and evaluation of Myc and Bcl-2 expression is necessary to predict the prognosis of DLBCL patients. PMID- 26541275 TI - Sedation protocols to reduce duration of mechanical ventilation in the ICU: a Cochrane Systematic Review. AB - AIMS: Assess the effects of protocol-directed sedation management on the duration of mechanical ventilation and other relevant patient outcomes in mechanically ventilated intensive care unit patients. BACKGROUND: Sedation is a core component of critical care. Sub-optimal sedation management incorporates both under- and over-sedation and has been linked to poorer patient outcomes. DESIGN: Cochrane systematic review of randomized controlled trials. DATA SOURCES: Cochrane Central Register of Controlled trials, MEDLINE, EMBASE, CINAHL, Database of Abstracts of Reviews of Effects, LILACS, Current Controlled Trials and US National Institutes of Health Clinical Research Studies (1990-November 2013) and reference lists of articles were used. REVIEW METHODS: Randomized controlled trials conducted in intensive care units comparing management with and without protocol-directed sedation were included. Two authors screened titles, abstracts and full-text reports. Potential risk of bias was assessed. Clinical, methodological and statistical heterogeneity were examined and the random-effects model used for meta-analysis where appropriate. Mean difference for duration of mechanical ventilation and risk ratio for mortality, with 95% confidence intervals, were calculated. RESULTS: Two eligible studies with 633 participants comparing protocol-directed sedation delivered by nurses vs. usual care were identified. There was no evidence of differences in duration of mechanical ventilation or hospital mortality. There was statistically significant heterogeneity between studies for duration of mechanical ventilation. CONCLUSIONS: There is insufficient evidence to evaluate the effectiveness of protocol-directed sedation as results from the two randomized controlled trials were conflicting. PMID- 26541276 TI - TNF-alpha suppression and osteoprotegerin overexpression inhibits wear debris induced inflammation and osteoclastogenesis in vitro. AB - PURPOSE: Periprosthetic osteolysis, involving RANK/RANKL/osteoprotegerin (OPG) and TNF-alpha/NFkappaB signaling, contributes to bone resorption and inflammation. We constructed lentivirus vectors to inhibit TNF-alpha and enhance OPG expression and assessed their impacts on wear debris-induced inflammation and osteoclastogenesis in an osteoclast/osteoblast coculture system. METHODS: We transduced mouse osteoblastic MC3T3-E1 cells with Lenti-negative control (Lenti NC), Lenti-OPG or Lenti-siTNFalpha-OPG, and murine macrophage/monocyte RAW264.7 cells with Lenti-NC, Lenti-TNF-alpha siRNA or Lenti-siTNFalpha-OPG. Then, TNF alpha and OPG protein levels were evaluated by enzyme-linked immunosorbent assay. We cocultured transduced MC3T3-E1 and RAW264.7 cells in transwell chambers in the presence of 0.1 mg/mL Ti particles to investigate the capacity of TNF-alpha inhibition to reduce wear debris-induced inflammation. We also assessed mRNA levels TNF-alpha, IL-1beta, IL-6 and OPG by RT-PCR as well as osteoclastogenesis by tartrate-resistant acid phosphatase. RESULTS: Lenti-siTNFalpha-OPG ameliorated Ti-particle-induced expression of TNF-alpha, IL-1beta, IL-6 in MC3T3-E1/RAW264.7 cocultures, while enhancing mRNA and protein levels of OPG, and reducing the fraction of tartrate-resistant acid phosphatase (TRAP)+ cells. CONCLUSIONS: Lenti siTNFalpha-OPG can inhibit the wear debris-induced inflammatory responses and osteoclastogenesis in vitro, and may represent a promising therapeutic candidate for the treatment or prevention of wear particle-induced osteolysis. PMID- 26541277 TI - The synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells. AB - PURPOSE: In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues. METHODS: Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor. RESULTS: Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed. CONCLUSIONS: Differentiation of ASCs was shown by a modest increase in gene expression profiles. In general, BSCs expressed higher levels of chondrogenic gene expression than ASCs after 3 weeks. A greater effect on Col II and SOX9 mRNA expression was observed when combined loadings were applied. Results may be applied in determining the proper loading sequence for obtaining functional target cells in cartilage engineering applications. PMID- 26541278 TI - Low incidence of gastrointestinal bleeding and pump thrombosis in patients receiving the INCOR LVAD system in the long-term follow-up. AB - BACKGROUND: Left ventricular assist device (LVAD) implantation improves survival and quality of life in patients with advanced heart failure (HF). Despite these advantages, LVADs are not free from risks. Among all adverse events (AE), pump thrombosis and bleeding, especially of the gastrointestinal (GI) tract, have been reported to occur with increasing frequency in some CF-LVADs. The INCOR LVAD system is a third-generation, continuous flow, axial pump with active magnetic levitation, avoiding the potential downsides of mechanical bearings. METHODS: The aim of this retrospective study was to review the Italian clinical experience with the INCOR LVAD and to determine the prevalence of GI bleeding and pump thrombosis. All patients implanted between January 2006 and May 2012 were considered eligible. RESULTS: The total population consisted of 42 patients. LVAD indication was BTT in 36 (86%) and DT in 6 (14%) patients; 31 patients (74%) were INTERMACS class 1 or 2. Mean support time was 525 +/- 570 days. The 1-year and 2 year survival rates were 74% and 60%, respectively. The most frequent AE was driveline infection (0.33 events PPY) followed by stroke with consequence (0.17 events PPY), sepsis (0.07 events PPY), and right HF (0.05 events PPY). No episodes of pump thrombosis or GI bleeding were observed. CONCLUSIONS: In this cohort of high-risk, advanced HF patients, the INCOR LVAD provided effective support with improved survival. Moreover, the absence of GI bleeding and pump thrombosis demonstrates a favorable characteristic of this device. Further prospective studies are needed to confirm these data. PMID- 26541279 TI - Effect of pulmonary conduit oversizing on hemodynamics in children. AB - PURPOSE: Implanting the largest valved conduit possible - oversizing - to reconstruct an absent connection from the right ventricle to the pulmonary artery in certain types of congenital heart defects has been suggested as a compensating measure for somatic outgrowth of the patient. However, one effect that has not been investigated yet is the hemodynamic consequence. For this purpose, virtual implantation and flow simulations were conducted in this study. METHODS: To isolate the effects of conduit oversizing on the hemodynamics observed after conduit implantation and outgrowth, calculated wall shear stresses (WSS) of image based computational fluid dynamic (CFD) simulations were used as indicators. Three different sizes of valved conduits (20 mm, 22 mm, and 24 mm), including the largest possible conduit size, virtually implanted in a child-sized healthy pulmonary artery and the corresponding adult-sized model were investigated. RESULTS: The child and adult models show a decrease of the mean WSS (approx. 26%) in the whole domain with an increase of the conduit size. When looking at the mean WSS at the anastomosis, for the child model the WSS is significantly increased (approx. 40%) when oversizing (Z-score +3.21). In contrast, the stresses are decreased for the adult model (34%) when using the largest conduit (Z-score +0.25). CONCLUSIONS: Based on the results of this study, it must be considered that choosing a prosthesis size that will lead to high WSS and an associated intimal reaction, possibly leading to stenosis, can defeat the benefit of having a nominally larger orifice area directly after implantation. PMID- 26541280 TI - Improved effect of continuous renal replacement therapy in metabolic status and body composition of early phase of acute pancreatitis. AB - OBJECTIVE: To observe the metabolic changes in the early phase of acute pancreatitis (AP) patients induced by continuous renal replacement therapy (CRRT), and to investigate the correlation between the metabolic changes and outcomes of the AP patients. METHODS: We performed a retrospective analysis in the surgical intensive care unit (ICU) of a tertiary teaching hospital. A total of 169 patients diagnosed as AP were divided into 2 groups: CRRT group (n = 71) and non-CRRT group (n = 98), based on whether they received CRRT for more than 24 hours within 7 days from onset of AP. Measured energy expenditure was measured by indirect calorimetry and predicted energy expenditure was determined by specific equations on admission and day 7 (or the closest day to day 7), respectively. Meanwhile, the body composition was measured by multiple-frequency bioelectrical impedance analyzer. Blood test, body weight and vital signs were analyzed daily for both groups. RESULTS: In this study, we found a significant improvement in the hypermetabolism and fluid distribution of the CRRT group compared with the non-CRRT group. Complications, hospital and ICU length of stays were reduced in CRRT patients. CONCLUSIONS: CRRT is an effective treatment for AP patients. Patients with overhydration and hypermetabolism may get improved outcomes from CRRT. PMID- 26541281 TI - Steroid treatment resolves acute respiratory failure in patient transferred for ECMO. AB - INTRODUCTION: Space-consuming mediastinal tumors can create respiratory failure. METHODS: We are reporting on a case of mediastinal lymphoma, which created respiratory failure in our patient. IV steroid therapy was used in our patient, who presented with end-stage respiratory failure. RESULTS: Conservative management of our patient was possible without the application of ECMO. CONCLUSIONS: In the right patient population, IV steroid treatment can avoid further deterioration of end-stage respiratory failure. PMID- 26541282 TI - In vitro evaluation of a novel pulsatile right heart assist device - the PERKAT system. AB - PURPOSE: Acute right ventricular failure is a life-threatening condition with poor prognosis. It occurs as a result of right ventricular infarction, postcardiac transplantation, or postimplantation of a left ventricular assist device. Temporary mechanical right ventricular support could be a reasonable treatment option. Therefore, we developed a novel percutaneously implantable device. METHODS: The PERKAT device consists of a self-expandable chamber covered with multiple inflow valves carrying foils. A flexible outlet tube with a pigtail tip is attached to the distal end. PERKAT is designed for percutaneous implantation through the femoral vein (18 French sheath). The chamber is expanded in the inferior vena cava while the outlet tube bypasses the right heart and the pigtail tip is lying in the pulmonary trunk. An IABP balloon is inserted into the chamber and connected to an IABP console. Balloon deflation generates blood flow from the vena cava into the chamber through the foil valves. During inflation blood is pumped through the tube into the pulmonary arteries. RESULTS: In vitro experiments were performed using 30 mL and 40 mL IABP balloons. IABP inflation/deflation times were set to 80, 90, 100, and 110 per min with an afterload of 22 mmHg and 44 mmHg. PERKAT generated flow rates between 1.6 to 3.1 l/min, depending on balloon size, pump cycle, and afterload. CONCLUSIONS: The novel percutaneously implantable right ventricular assist device offers emergency support of up to 3 l/min. Based on the successful in vitro evaluation, we recommend the system as a promising approach for treatment of patients in need of RV support. PMID- 26541283 TI - Thermanaeromonas burensis sp. nov., a thermophilic anaerobe isolated from a subterranean clay environment. AB - A strictly anaerobic, thermophilic and halotolerant strain, designated IA106T, was isolated from the seepage water collected in a metal biocorrosion test at a depth of 490 m, in a 130-160 m thick, subterranean Callovo-Oxfordian clay formation (158-152 million years old) in northern France. This geological formation has been selected as the potential host rock for the French high-level nuclear waste repository. Cells of strain IA106T stained Gram-positive and were non-motile, spore-forming, straight rods (0.5 * 2-6 MUm). The five major fatty acids were C16 : 0 (15.9 %), C18 : 0 (15.4 %), iso-C17 : 1 I and/or anteiso-C17 : 1 B(14.8 %), iso-C17 : 0 (14.7 %) and iso-C15 : 0 (13.0 %). Growth was observed at temperatures ranging from 55 to 70 degrees C and at pH 5.5-9. The salinity range for growth was 0-20 g NaCl 1- 1. Yeast extract was required for growth. Strain IA106T was able to grow on lactate and various sugars in the presence of thiosulfate as electron acceptor. Sulfate, sulfite, elemental sulfur, fumarate, nitrate and nitrite were not reduced. The DNA G+C content was 60.2 mol%. 16S rRNA gene sequence analysis indicated that strain IA106T belonged to the family Thermoanaerobacteraceae, class Clostridia, phylum Firmicutes, and was most closely related to Thermanaeromonas toyohensis DSM 14490T (95.16 % 16S rRNA gene sequence similarity). On the basis of 16S rRNA gene sequence comparisons and physiological characteristics, strain IA106T represents a novel species of the genus Thermanaeromonas, for which the name Thermanaeromonas burensis sp. nov. is proposed. The type strain is IA106T ( = DSM 26576T = JCM 18718T). PMID- 26541284 TI - Synthesis, structure and enhanced photoluminescence properties of two robust, water stable calcium and magnesium coordination networks. AB - Two new 3D coordination networks Ca(cca).H2O (1) and Mg(cca).2H2O (2) (H2cca = 4 carboxycinnamic acid) are synthesized by solvothermal reactions and characterized by single crystal and powder X-ray diffraction, thermogravimetric analysis, optical diffuse reflection, photoluminescence spectroscopy, and internal quantum yield measurements. Crystal structure analysis reveals that compound 1 is built from edge-sharing chains of seven-coordinated calcium polyhedra, which are connected by the cca ligand to form a 2D layered structure. Compound 2 contains isolated magnesium polyhedra layers. These layers are linked by cca ligands to complete the 3D connectivity. Both compounds 1 and 2 have high thermal stability and remain intact in aqueous solutions of a broad range of pH values ranging from 3 to 11. Both compounds also show significantly enhanced luminescence with respect to the free ligand, giving rise to an increase in quantum yield by as much as 4-fold. PMID- 26541285 TI - Cotton rat immune responses to virus-like particles containing the pre-fusion form of respiratory syncytial virus fusion protein. AB - BACKGROUND: Virus-like particles (VLPs) based on Newcastle disease virus (NDV) core proteins, M and NP, and containing two chimera proteins, F/F and H/G, composed of the respiratory syncytial virus (RSV) fusion protein (F) and glycoprotein (G) ectodomains fused to the transmembrane and cytoplasmic domains of the NDV F and HN proteins, respectively, stimulate durable, protective anti RSV neutralizing antibodies in mice. Furthermore, immunization of mice with a VLP containing a F/F chimera protein with modifications previously reported to stabilize the pre-fusion form of the RSV F protein resulted in significantly improved neutralizing antibody titers over VLPs containing the wild type F protein. The goal of this study was to determine if VLPs containing the pre fusion form of the RSV F protein stimulated protective immune responses in cotton rats, a more RSV permissive animal model than mice. METHODS: Cotton rats were immunized intramuscularly with VLPs containing stabilized pre-fusion F/F chimera protein as well as the H/G chimera protein. The anti-RSV F and RSV G antibody responses were determined by ELISA. Neutralizing antibody titers in sera of immunized animals were determined in plaque reduction assays. Protection of the animals from RSV challenge was assessed. The safety of the VLP vaccine was determined by monitoring lung pathology upon RSV challenge of immunized animals. RESULTS: The Pre-F/F VLP induced neutralizing titers that were well above minimum levels previously proposed to be required for a successful vaccine and titers significantly higher than those stimulated by RSV infection. In addition, Pre-F/F VLP immunization stimulated higher IgG titers to the soluble pre-fusion F protein than RSV infection. Cotton rats immunized with Pre-F/F VLPs were protected from RSV challenge, and, importantly, the VLP immunization did not result in enhanced respiratory disease upon RSV challenge. CONCLUSIONS: VLPs containing the pre fusion RSV F protein have characteristics required for a safe, effective RSV vaccine. PMID- 26541286 TI - High-frequency, precise modification of the tomato genome. AB - BACKGROUND: The use of homologous recombination to precisely modify plant genomes has been challenging, due to the lack of efficient methods for delivering DNA repair templates to plant cells. Even with the advent of sequence-specific nucleases, which stimulate homologous recombination at predefined genomic sites by creating targeted DNA double-strand breaks, there are only a handful of studies that report precise editing of endogenous genes in crop plants. More efficient methods are needed to modify plant genomes through homologous recombination, ideally without randomly integrating foreign DNA. RESULTS: Here, we use geminivirus replicons to create heritable modifications to the tomato genome at frequencies tenfold higher than traditional methods of DNA delivery (i.e., Agrobacterium). A strong promoter was inserted upstream of a gene controlling anthocyanin biosynthesis, resulting in overexpression and ectopic accumulation of pigments in tomato tissues. More than two-thirds of the insertions were precise, and had no unanticipated sequence modifications. Both TALENs and CRISPR/Cas9 achieved gene targeting at similar efficiencies. Further, the targeted modification was transmitted to progeny in a Mendelian fashion. Even though donor molecules were replicated in the vectors, no evidence was found of persistent extra-chromosomal replicons or off-target integration of T-DNA or replicon sequences. CONCLUSIONS: High-frequency, precise modification of the tomato genome was achieved using geminivirus replicons, suggesting that these vectors can overcome the efficiency barrier that has made gene targeting in plants challenging. This work provides a foundation for efficient genome editing of crop genomes without the random integration of foreign DNA. PMID- 26541287 TI - Prevalence of intestinal parasites among patients of a Ghanaian psychiatry hospital. AB - BACKGROUND: Neglected tropical diseases are of major concern to sub-Saharan African countries. Though efforts to monitor the prevalence and control are in place, these are mostly restricted to groups within the population. This study was performed to determine the prevalence among patients of a Ghanaian psychiatric hospital and find out whether there is a reason for active monitoring in this population. METHODS: A cross-sectional study was performed to determine the prevalence of intestinal parasites among patients of a Ghanaian psychiatric hospital. Stool samples were collected and analyzed in addition to data. RESULTS: Of the 111 patients studied, asymptomatic carriage of parasites was 13.5 % and was higher in males (18.8 %) than in females (4.8 %). Carriage of parasites decreased with age but increase with duration of admission. CONCLUSION: This is the first report of parasitic pathogens among patients of a psychiatric institution in Ghana. The data shows that there are risks of transmission of infectious diseases via the oral route hence, the need for regular monitoring and intervention is emphasized. PMID- 26541288 TI - An institutional ethnography of chronic pain management in family medicine (COPE) study protocol. AB - BACKGROUND: Patients with chronic conditions and multiple comorbidities represent a growing challenge for health care globally. Improved coordination of care is considered essential for providing more effective and cost-efficient care for these patients with complex needs. Osteoarthritis is one of the most common and debilitating chronic conditions, is the most frequent cause of chronic pain yet osteoarthritis care is often poorly-coordinated. Primary care is usually the first contact for patients requiring relief from chronic pain. Our previous work suggests discordance between the policy goals of improving patient care and the experience of osteoarthritis patients. We plan to investigate the empirical context of the primary care setting by focusing on primary physicians' conceptualizations and performance of their work in treating complex patients with chronic pain. This will allow for an exploration of how primary health care is - or could be - integrated with other services that play an important role in health care delivery. METHODS: Our study is an Institutional Ethnography of pain management in family medicine, to be carried out in three phases over 3 years from 2014/15 to 2018. Over the first year we will undertake approximately 80 key informant interviews with primary care physicians, other health care providers, policymakers and clinical experts. In the second year we will focus on mobilizing our networks from year one to assist in the collection of key texts which shape the current context of care. These texts will be analyzed by the research team. In the final year of the study we will focus on synthesizing our findings in order to map the social relations informing care. As is standard and optimal in qualitative research, analysis will be concurrent with data collection. DISCUSSION: Our study will allow us to identify how the work of coordinating care across multiple settings is accomplished, in practice as well as discursively and textually. Ultimately, we will identify links between everyday experience of care for patients with chronic pain, and broader discourses related to health care system inefficiencies, integration and patient-centred care. An expected outcome of this study will be the development of new, or augmentation of existing, models of care, that are based in the local realities of primary care practice. PMID- 26541289 TI - Early and mid-term outcome in terms of functional and hemodynamic performance of the st. Jude regent 19-mm aortic mechanical prosthesis versus 19-mm carpentier edwards aortic biological prosthesis. AB - BACKGROUND: The aim of the present study is to compare the early and mid-term clinical and hemodynamic results of the aortic valve replacement (AVR) with a St Jude Medical Regent 19-mm prosthesis (SJMR-19) versus Carpentied-Edwars bovine pericardial 19-mm valve (CE-19). METHODS: Between January 2002 and January 2012, 265 patients (Group I) and 58 patients (Group II) with underwent AVR with a SJMR 19 and CE-19 respectively. There were no significant differences between groups regarding the demographic and preoperative echocardiographic data. Thirty-six patients in Group I and 4 in Group II required annulus enlargement in association or not with septal myectomy. The mean follow-up was 34 +/- 18.5 months (range 5 60 months). RESULTS: There were 14 (5.3 %) hospital deaths in Group I versus 4 (6.8 %) in Group II (p = 0.86). The multivariate logistic regression analysis identified the LVEF <= 35 % (p = 0.001), combined operation (p = 0.0005), CPB (p = 0.033), age (p = 0.011), annulus enlargement (p = 0.0009), reoperation (p = 0.039) and chronic renal failure (p = 0.011) as strong predictors for early postoperative death. Within 1 year after surgery peak pulmonary artery pressure, interventricular septal and left ventricular posterior wall thickness decreased significantly in both groups. The M-TPG was 15.7 +/- 6.5 mmHg in Group I versus 17 +/- 7 mmHg in Group II (p = 0.19). The multivariate regression analysis revealed the annulus enlargement (p = 0.018), small EOAi (p = 0.00004), postoperative LVMi (p = 0.0001) and BSA (p = 0.019) as strong predictors for higher M-TPG. The postoperative LVMi was 119 +/- 22.5 gm/m(2) in Group I and 122 +/- 22 gm/m(2) in Group II (p = 0.37), significantly lower than the respective preoperative values 162.5 +/- 34 gm/m(2) (Group I) and 168 +/- 30 gm/m(2) (Group II). The actuarial survival and cumulative free-reoperation actuarial survival at 5 years follow-up were 96.7 and 94.5 % respectively in Group I and 97 and 91 % in Group II.. There were non significant differences between groups regarding the actuarial survival and cumulative free-reoperation survival. The Cox model identified the older age (p = 0.022), LVEF <= 35 % (p = 0.009), reoperation (p = 0.018), combined surgery (p = 0.00075) and annulus enlargement (p = 0.033) as strong predictors for poor actuarial free-reoperation survival. CONCLUSIONS: Both the SJMR-19 and CE-19 offers excellent postoperative clinical and hemodynamic outcome in patients with small aortic annulus. The LV hypertrophy and transvalvular gradients are reduced significantly indenpendently of the employed SJMR-19 or CE-19 prosthesis. Our data support recent suggestions that small valve size does not influence intermediate free-reoperation survival. The CE-19 is an excellent alternative to SJMR-19 in old patients. PMID- 26541290 TI - A prospective study on histone gamma-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome. AB - BACKGROUND: The prognostic value of histone gamma-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone gamma-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. METHODS: Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of gamma-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references. RESULTS: The gamma-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients. CONCLUSIONS: The study shows higher expression of gamma-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome. PMID- 26541291 TI - Comprehensive transcriptional landscape of aging mouse liver. AB - BACKGROUND: Mammalian aging is a highly complex process, a full mechanistic understanding of which is still lacking. One way to help understand the molecular changes underlying aging is through a comprehensive analysis of the transcriptome, the primary determinant of age-related phenotypic diversity. Previous studies have relied on microarray analysis to examine gene expression profiles in different tissues of aging organisms. However, studies have shown microarray-based transcriptional profiling is less accurate and not fully capable of capturing certain intricacies of the global transcriptome. METHODS: Here, using directional whole transcriptome RNA-sequencing of aged mouse liver we have identified a comprehensive high-resolution profile of differentially expressed liver transcripts comprised of canonical protein-coding transcripts, transcript isoforms, and non-coding RNA transcripts, including pseudogenes, long non-coding RNAs and small RNA species. RESULTS: Results show extensive age-related changes in every component of the mouse liver transcriptome and a pronounced increase in inter-individual variation. Functional annotation of the protein-coding mRNAs and isoforms indicated broad alterations in immune response, cell activation, metabolic processes, and RNA modification. Interestingly, multiple lncRNAs (Meg3, Rian, Mirg) from the Dlk-Dio3 microRNA locus were found up-regulated in aging liver, classifying this locus as a putative regulatory hotspot locus in aging liver. Moreover, integration of the altered non-coding RNAs and protein-coding transcripts into interaction networks of age-related change revealed inflammation, cellular proliferation, and metabolism as the dominant aging phenotypes in mouse liver. CONCLUSIONS: Our analyses provide the first comprehensive dissection of the transcriptional landscape in aging mouse liver. PMID- 26541293 TI - Improved maximum entropy method for the analysis of fluorescence spectroscopy data: evaluating zero-time shift and assessing its effect on the determination of fluorescence lifetimes. AB - A new algorithm based on the Maximum Entropy Method (MEM) is proposed for recovering both the lifetime distribution and the zero-time shift from time resolved fluorescence decay intensities. The developed algorithm allows the analysis of complex time decays through an iterative scheme based on entropy maximization and the Brent method to determine the minimum of the reduced chi squared value as a function of the zero-time shift. The accuracy of this algorithm has been assessed through comparisons with simulated fluorescence decays both of multi-exponential and broad lifetime distributions for different values of the zero-time shift. The method is capable of recovering the zero-time shift with an accuracy greater than 0.2% over a time range of 2000 ps. The center and the width of the lifetime distributions are retrieved with relative discrepancies that are lower than 0.1% and 1% for the multi-exponential and continuous lifetime distributions, respectively. The MEM algorithm is experimentally validated by applying the method to fluorescence measurements of the time decays of the flavin adenine dinucleotide (FAD). PMID- 26541292 TI - Inequalities in medicine use in Central Eastern Europe: an empirical investigation of socioeconomic determinants in eight countries. AB - BACKGROUND: Equitable access to essential medicines is a major challenge for policy-makers world-wide, including Central and Eastern European countries. Member States of the European Union situated in Central and Eastern Europe have publicly funded pharmaceutical reimbursement systems that should promote accessibility and affordability of, at least essential medicines. However, there is no knowledge whether socioeconomic inequalities exist in these countries. Against this backdrop, this study analyses whether socioeconomic determinants influence the use of prescribed and non-prescribed medicines in eight Central and Eastern European countries (Bulgaria, Czech Republic, Hungary, Latvia, Poland, Romania, Slovenia, Slovakia). Further, the study discusses observed (in)equalities in medicine use in the context of the pharmaceutical policy framework and the implementation in these countries. METHODS: The study is based on cross-sectional data from the first wave of the European Health Interview Survey (2007-2009). Multivariate logistic regression analyses were carried out to determine the association between socioeconomic status (measured by employment status, education, income; controlled for age, gender, health status) and medicine use (prescribed and non-prescribed medicines). This was supplemented by a pharmaceutical policy analysis based on indicators in four policy dimensions (sustainable funding, affordability, availability and accessibility, and rational selection and use of medicines). RESULTS: Overall, the analysis showed a gradient favouring individuals from higher socioeconomic groups in the consumption of non prescribed medicines in the eight surveyed countries, and for prescribed medicines in three countries (Latvia, Poland, Romania). The pharmaceutical systems in the eight countries were, to varying degrees, characterized by a lack of (public) funding, thus resulting in high and growing shares of private financing (including co-payments for prescribed medicines), inefficiencies in the selection of medicines into reimbursement and limitations in medicines availability. CONCLUSION: Pharmaceutical policies aiming at reducing inequalities in medicine use require not only a consideration of the role of co-payments and other private expenditure but also adequate investment in medicines and transparent and clear processes regarding the inclusion of medicines into reimbursement. PMID- 26541294 TI - Localized-surface-plasmon-enhanced multifunction silicon nanomembrane Schottky diodes based on Au nanoparticles. AB - Au nanoparticle (NP)-modified Si nanomembrane (Si NM) Schottky barrier diodes (SBDs) were fabricated by using a transfer-printing method to create pedestals using only one photomask on a flexible substrate. The transfer using the pedestals afforded a yield of >95% with no significant cracks. The plasmonic Au NPs can facilitate the improvement of the incident optical absorption. The Au NP modified Si NM SBD exhibited enhanced photoresponse characteristics with an external quantum efficiency (eta(EQE)) of 34%, a photosensitivity (P) of 27 at a voltage bias of -5 V, a light intensity of 1.2 W cm(-2), and a responsivity (R(ph)) of 0.21 A W(-1). Additionally, the mechanical bending characteristics of the device were observed while a compressive strain up to 0.62% was applied to the diode. The results suggest that the Au NP-modified Si NM SBD has great potential for use in multifunction devices as a strain sensor and photosensor. PMID- 26541295 TI - Migrated esophageal foreign body presents as acute onset dysphagia years later: A case report. AB - Ingested esophageal foreign bodies are commonly seen in the pediatric population. Rarely do they perforate and migrate through neck fascial planes asymptomatically. We present a case of an otherwise healthy 11 year old with sudden onset dysphagia that based on MRI and CT findings was most consistent with an esophageal duplication cyst. However upon surgical exploration, a circular disk like foreign body was identified adjacent to the esophagus. Given the patient's age and no reports of purposeful ingestion, it is most likely the patient had ingested this disk foreign body in early childhood, leaving her asymptomatic for 8 years prior to presentation. PMID- 26541296 TI - Nasal fractures in children and adolescents: Mechanisms of injury and efficacy of closed reduction. AB - OBJECTIVES: To determine the most common mechanisms of traumatic nasal deformity referred to pediatric otolaryngology. To examine the efficacy of closed reduction of nasal fractures in children and adolescents based on the parents' and surgeons' ratings of post-reduction nasal symmetry. METHODS: Case series and chart review within an urban, tertiary pediatric otolaryngology practice. RESULTS: 100 cases of traumatic nasal deformity met inclusion criteria over a 3 year study period. The mean age at presentation was 13 years (4 weeks-18 years); 55% were male and 70% were over the age of 12 years. The most common mechanism of injury was sports-related trauma (28%), followed by accidental trauma (21%), interpersonal violence (10%), motor vehicle collision (6%) and alcohol-related (2%). Of these 100 cases, 22% underwent closed reduction within a 14-day period following injury. All patients achieved symmetry in the operating room immediately following reduction. 21 of 22 post-reduction patients were assessed for nasal symmetry at the postoperative visit (7-10 days following surgery). The operating surgeon was satisfied with nasal symmetry in 43% of cases and the parent(s) satisfied in 81% of cases. Both parent and surgeon were satisfied with post-reduction symmetry 33% of the time. CONCLUSION: The most common sources of traumatic nasal deformity in children and adolescents vary by age. In cases meriting operative intervention, parents appear to be satisfied with early postoperative results following closed reduction in approximately 80% of cases, however a result in which both parent and surgeon agree with successful re establishment of symmetry occurs in only one-third of cases. PMID- 26541297 TI - Amperometric monitoring of quercetin permeation through skin membranes. AB - Transdermal delivery of quercetin (QR, 3,3',4',5,7-pentahydroxyflavone), a natural flavonoid with a considerable antioxidant capacity, is important for medical treatment of, e.g., skin disorders. QR permeability through skin is low, which, at the same time, makes the monitoring of percutaneous QR penetration difficult. The objective of this study was to assess an electrochemical method for monitoring QR penetration through skin membranes. An electrode was covered with the membrane, exposed to QR solution, and electrode current was measured. The registered current was due to electro-oxidation of QR penetrating the membrane. Exploiting strict current-QR flux relationships diffusion coefficient, D, of QR in skin and dialysis membranes was calculated. The D values were strongly dependent on the theoretical model and parameters assumed in the processing of the amperometric data. The highest values of D were in the range of 1.6-6.1*10(-7)cm(2)/s. This was reached only for skin membranes pretreated with buffer-ethanol mixture for more than 24h. QR solutions containing penetration enhancers, ethanol and l-menthol, definitely increased D values. The results demonstrate that electrochemical setup gives a possibility to assess penetration characteristics as well as enables monitoring of penetration dynamics, which is more difficult by traditional methods using Franz cells. PMID- 26541298 TI - Will the use of double barrier result in sustained release of vancomycin? Optimization of parameters for preparation of a new antibacterial alginate-based modern dressing. AB - The aim of this research was to prepare and characterize an alginate-based wound dressing containing vancomycin immobilized at the silica surface. The silica samples functionalized with amine, diol and carboxylic acid groups were loaded with 7.8, 5.7 and 7.1wt.% of the antibiotic respectively. The immobilized drug was encapsulated in alginate or gelatin/alginate gels and the average concentration of vancomycin was about 10mg per g of the dried gel. The effect of functional organic groups at the silica surface on the release rate of the drug was investigated. Only the drug immobilized at Si-amine in alginate matrix was found to demonstrate slower release from the proposed wound dressing. The in vitro release profiles for other silica carriers did not show significant differences in relation to the free loaded drug. The presence of gelatin had a favourable impact on the slowing down of the drug release from the dressing with a double barrier. All the gels studied with vancomycin immobilized at the silica surface demonstrated antimicrobial activity against various bacteria. A reduction of the drug dose to a half had no effect on changing microbiological activity of gels. PMID- 26541299 TI - Goblet cell targeting nanoparticle containing drug-loaded micelle cores for oral delivery of insulin. AB - Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin loaded dodecylamine-graft-gamma-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitro evaluation, Caco 2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%. PMID- 26541300 TI - Green fabricated reduced graphene oxide: evaluation of its application as nano carrier for pH-sensitive drug delivery. AB - A green and mild approach for the preparation of reduced graphene oxide (rGO) was proposed by using riboflavin-5'-phosphate sodium salt dihydrate as a reducing reagent and stabilizer without any other reagent. The fabricated nano-rGO was systematically evaluated for its application as nano-carrier for pH-sensitive drug delivery. The hemolytic toxicity test indicated the as-prepared nano-rGO had negligible hemolytic activity, which demonstrating its safety in drug delivery system. Doxorubicin hydrochloride (DOX) as a model drug was successfully attached onto the surface of nano-rGO via strong pi-pi stacking interaction. Compared with common carriers, the obtained DOX-loaded nano-rGO nanohybrid exhibited characteristics of high drug loading content, good stability, pH-sensitive and sustainable release of drugs. Cytotoxicity assay results suggested such nanohybrid exhibited effective cytotoxicity to MCF-7 and A549 cells by nonspecific endocytosis mechanism. Therefore, the present green fabricated rGO could be a good candidate as an ideal nano-carrier for drug delivery and controlled release. PMID- 26541302 TI - Influence of in line monitored fluid bed granulation process parameters on the stability of Ethinylestradiol. AB - Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability. PMID- 26541301 TI - Printing medicines as orodispersible dosage forms: Effect of substrate on the printed micro-structure. AB - We present our recent advancements in developing a viable manufacturing process for printed medicine. Our approach involves using a non-contact printing system that incorporates both piezoelectric- and solenoid valve-based inkjet printing technologies, to deliver both active and inactive pharmaceutical materials onto medical-graded orodispersible films. By using two complimentary inkjet technologies, we were able to dispense an extensive range of fluids, from aqueous drug solutions to viscous polymer coating materials. Essentially, we demonstrate printing of a wide range of formulations for patient-ready, orodispersible drug dosage forms, without the risk of drug degradation by ink heating and of substrate damages (by contact printing). In addition, our printing process has been optimized to ensure that the drug doses can be loaded onto the orally dissolvable films without introducing defects, such as holes or tears, while retaining a smooth surface texture that promotes patient adherence and allows for uniform post-coatings. Results show that our platform technology can address key issues in manufacturing orodispersible drug dosage forms and bring us closer to delivering personalized and precision medicine to targeted patient populations. PMID- 26541303 TI - Antibody fragment-armed mesoporous silica nanoparticles for the targeted delivery of bevacizumab in ovarian cancer cells. AB - In order to enhance the therapeutic efficacy and intracellular concentration of bevacizumab (BVC), we have designed a novel tumor endothelial marker 1 (TEM1)/endosialin (Ab-/scFv)-conjugated mesoporous silica nanoparticles (MSN) to target ovarian cancer cell. The Ab-/scFv-conjugated MSN were prepared by the conjugation of amine functional group of antibody of the carboxyl group of MSN. The resultant MSN was nanosized, spherical shaped, and exhibited a controlled release phenomenon in pH 7.4 conditions. Furthermore, BMSN/Ab was found to increase the cellular uptake and intracellular distribution of BVC in OVCAR-5 cancer cells. The Ab- conjugated MSN exhibited a superior anticancer effect with profound apoptosis in cancer cells in a time- and concentration dependent manner. Consistently, BMSN/Ab effectively inhibited the colony formation in transwell plate. Finally, BMSN/Ab showed a notable increase in the proportion of cells in G2/M phase of cell cycle indicating promising anticancer efficacy profile. Overall, Ab-/scFv-conjugated MSN might provide an effective strategy for the therapeutic management of ovarian cancers. PMID- 26541304 TI - Ex-vivoand in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base. AB - The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichia coli and Staphylococcus aureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system. PMID- 26541305 TI - New polymorphs of 9-nitro-camptothecin prepared using a supercritical anti solvent process. AB - Recrystallization and micronization of 9-nitro-camptothecin (9-NC) has been investigated using the supercritical anti-solvent (SAS) technology in this study. Five operating factors, i.e., the type of organic solvent, the concentration of 9 NC in the solution, the flow rate of 9-NC solution, the precipitation pressure and the temperature, were optimized using a selected OA16 (4(5)) orthogonal array design and a series of characterizations were performed for all samples. The results showed that the processed 9-NC particles exhibited smaller particle size and narrower particle size distribution as compared with 9-NC raw material (Form I), and the optimum micronization conditions for preparing 9-NC with minimum particle size were determined by variance analysis, where the solvent plays the most important role in the formation and transformation of polymorphs. Three new polymorphic forms (Form II, III and IV) of 9-NC, which present different physicochemical properties, were generated after the SAS process. The predicted structures of the 9-NC crystals, which were consistent with the experiments, were performed from their experimental XRD data by the direct space approach using the Reflex module of Materials Studio. Meanwhile, the optimal sample (Form III) was proved to have higher cytotoxicity against the cancer cells, which suggested the therapeutic efficacy of 9-NC is polymorph-dependent. PMID- 26541306 TI - Clinical Neurophysiology in an era of change. PMID- 26541307 TI - EEG alpha power during maintenance of information in working memory in adults with ADHD and its plasticity due to working memory training: A randomized controlled trial. AB - OBJECTIVE: The present study examined whether neural indices of working memory maintenance differ between young adults with ADHD and their healthy peers (Study 1), and whether this neural index would change after working memory training (Study 2). METHODS: Study 1 involved 136 college students with ADHD and 41 healthy peers (aged 18-35 years) and measured their posterior alpha activity during a visual delayed-match-to-sample task using electroencephalography (EEG). Study 2 involved 99 of the participants with ADHD who were randomized into a standard-length or shortened-length Cogmed working memory training program or a waitlist control group. RESULTS: The ADHD group tended to be less accurate than the peers. Similarly, the ADHD group exhibited lower posterior alpha power at a trend level compared to their healthy peers. There were no training effects on participants' performance and only marginal increases in posterior alpha power in training groups compared to the waitlist group. CONCLUSIONS: Considering that the training effects were small and there was no load and dose effect, we conclude that the current study provides no convincing evidence for specific effects of Cogmed. SIGNIFICANCE: These findings provide unique insights into neuroplasticity, or lack thereof, with near-transfer tasks in individuals with ADHD. PMID- 26541308 TI - Functional connectivity assessed by resting state EEG correlates with cognitive decline of Alzheimer's disease - An eLORETA study. AB - OBJECTIVE: To explore neurophysiological biomarkers of Alzheimer's disease (AD), we investigated electroencephalography (EEG) of AD patients, and assessed lagged phase synchronization, a measure of brain functional connectivity. METHODS: Twenty-eight probable AD patients and 30 healthy controls (HC) were enrolled. Forty seconds of artifact-free EEG data were selected and compared between patients with AD and HC. Current source density (CSD) and lagged phase synchronization were analyzed by using eLORETA. RESULTS: Patients with AD showed significantly decreased lagged phase synchronization between most cortical regions in delta band relative to controls. There also was a decrease in lagged phase synchronization between the right dorsolateral prefrontal cortex (DLPFC) and the right posterior-inferior parietal lobule (pIPL) in theta band. In addition, some connections in delta band were found to be associated with cognitive function, measured by MMSE. This involved specifically interhemispheric temporal connections as well as left inferior parietal connectivity with the left hippocampus, lateral frontal regions, and the anterior cingulate cortex (aCC). Right temporal connections in delta band were related to global function, as estimated by CDR. No differences were found in CSD analysis between patients and HC. CONCLUSIONS: Functional connectivity disruptions between certain brain regions, as measured with lagged phase synchronization, may potentially represent a neurophysiological biomarker of AD. SIGNIFICANCE: Our study indicated that AD and healthy elderly could have the different patterns of lagged phase synchronization. PMID- 26541309 TI - Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma. AB - BACKGROUND: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci. RESULTS: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013). CONCLUSIONS: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer. PMID- 26541310 TI - [Effects of cognitive state on balance disturbances and gait disorders in institutionalised elderly]. AB - BACKGROUND: Ageing has been linked to a high prevalence of cognitive impairment, which, in turn, has been related to balance disturbances and gait disorders. The aim of this study was to identify whether there are differences between subjects with and without cognitive impairment regarding the quality of gait and balance. MATERIAL AND METHODS: An observational study was conducted on institutionalised people older than 65 years (n=82). Gait and balance was evaluated after the assessment of cognitive impairment using the Mini-Mental State Examination (MMSE). Single and dual tests were used including, the 6-minute walking, stride length, and gait speed. Timed Up and Go tests were also used to evaluate balance. RESULTS: The participants were divided into three groups: 28 subjects in the group without cognitive impairment (MMSE>=27), 29 subjects with mild (2770%) are absorbed by albumin, which transports them to the liver for disposal. When the amount of PHB in the diet exceed the capacity of albumin to safely remove them from the circulation, the excess PHB remain in the lipid core of LDL particles that become constituents of lipoprotein Lp(a), and contribute to the formation of arterial deposits. In summary, the presence of PHB - water insoluble, dense, viscous, adhesive polymers - in the lipid cores of the LDL moieties of Lp(a) particles supports the hypothesis that PHB are atherogenic components of Lp(a). PMID- 26541315 TI - Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence. AB - The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). PMID- 26541316 TI - New broadly reactive neutralizing antibodies against hepatitis B virus surface antigen. AB - Hepatitis B virus (HBV) surface antigen (HBsAg) is considered to be the most important target for the diagnosis and immune prophylaxis of HBV infection. HBsAg specific monoclonal antibodies (MAbs) are extensively used for studying the complex structure of the HBsAg, mapping the neutralizing epitopes and development of HBV diagnostic tests. However, the efficiency of anti-HBV binding strongly depends on the epitope structure and MAb capability to recognize different HBV variants. In the current study, 9 MAbs against yeast-expressed HBsAg of ayw2 serotype were generated and 7 of them were shown to recognize a linear epitope comprising amino acid (aa) residues 119-GPCRTCT-125 within the main antigenic "a" determinant of HBsAg. One MAb of the highest affinity (clone HB1) was selected for detailed cross-reactivity studies, generation of recombinant single-chain antibody (scFv) and molecular modelling of antibody-epitope interaction. The importance of each aa residue within the identified MAb epitope was determined by alanine substitution study that revealed aa residues C(121), T(123), C(124) and T(125) as essential for binding. These aa residues are highly conserved among HBV variants. In contrast, alanine substitution of G119, P120 and R122 had no or minor influence on the reactivity with the MAb. Certain aa residues at position 122 (either R or K) define different HBV serotypes (either d or y), therefore, the affinity of the MAb HB1 for the epitope with R122K substitution was determined to evaluate its diagnostic potential. The MAb recognized both epitope variants with high affinity. Sequence alignment of the MAb epitope within different HBV strains demonstrated that the shortest peptide recognized by the MAb 121-CR(K)TCT-125 is identical among different human HBV genotypes (HBV A-F, H) and monkey HBV species (HBVCP, HBVGO, HBVGB, WMHBV). In line with these data, the MAb HB1 was cross-reactive in Western blot with a large panel of antigens derived from different HBV genotypes. Recombinant scFv consisting of immunoglobulin VH and VL regions joined by a 20 aa-long linker was generated by cloning the respective cDNA sequences from hybridoma HB1. The recombinant scFv generated in Escherichia coli recognized the same epitope as the parental MAb HB1. Cloning of HB1 VH and VL regions allowed determination of their primary structure and subsequent computer modeling of antibody-epitope interaction. The generated molecular models of HB1 variable region with its target peptides were in accordance with experimental data showing the importance of certain aa residues in antibody binding. In conclusion, the current study describes new HBsAg-specific antibodies with HBV-neutralizing potency and a broad cross reactivity against different HBV strains. The generated MAb HB1 will be of great value in diagnostic and research settings, while the recombinant HB1-derived scFv represents a promising "building block" for producing anti-HBV tools with a potential biopharmaceutical application. PMID- 26541317 TI - Potential of phage cocktails in the inactivation of Enterobacter cloacae--An in vitro study in a buffer solution and in urine samples. AB - The objective of this study was to compare the dynamics of three previously isolated phages for Enterobacter cloacae in order to evaluate their ability to treat urinary tract infections (UTI). The phages genomes, survival, host range, were characterized, and the host-phage dynamics was determined in culture medium and urine samples. The presence of prophages in bacteria, host recovery and development of resistance to phage after treatment was also evaluated. The growth of the E. cloacae was inhibited by the three phages, resulting in a decrease of ~3 log. The use of cocktails with two or three phages was significantly more effective (decrease of ~4 log). In urine, the inactivation was still effective (~2 log). Both phages were considered safe to inactivate the bacteria (no integrase and toxin codifying genes). Some bacteria remained viable in the presence of the phages, but their colonies were smaller than those of the non treated control and were visible only after 5 days of incubation (visible after 24h in the control). A high bacterial inactivation efficiency with phage cocktails combined with the safety of the phages and their long periods of survival, even in urine samples, paves the way for depth studies, especially in vivo studies, to control urinary tract infection and to overcome the development of resistances by the nosocomial bacterium E. cloacae. PMID- 26541318 TI - Structural Mapping of Functional Ge Layers Grown on Graded SiGe Buffers for sub 10 nm CMOS Applications Using Advanced X-ray Nanodiffraction. AB - We report a detailed advanced materials characterization study on 40 nm thick strained germanium (Ge) layers integrated on 300 mm Si(001) wafers via strain relaxed silicon-germanium (SiGe) buffer layers. Fast-scanning X-ray microscopy is used to directly image structural inhomogeneities, lattice tilt, thickness, and strain of a functional Ge layer down to the sub-micrometer scale with a real space step size of 750 MUm. The structural study shows that the metastable Ge layer, pseudomorphically grown on Si(0.3)Ge(0.7), exhibits an average compressive biaxial strain of -1.27%. By applying a scan area of 100 * 100 MUm(2), we observe microfluctuations of strain, lattice tilt, and thickness of ca. +/-0.03%, +/-0.05 degrees , and +/-0.8 nm, respectively. This study confirms the high materials homogeneity of the compressively strained Ge layer realized by the step-graded SiGe buffer approach on 300 mm Si wafers. This presents thus a promising materials science approach for advanced sub-10 nm complementary metal oxide semiconductor applications based on strain-engineered Ge transistors to outperform current Si channel technologies. PMID- 26541319 TI - Relative contributions of L-FABP, SCP-2/SCP-x, or both to hepatic biliary phenotype of female mice. AB - Both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed to function in hepatobiliary bile acid metabolism/accumulation. To begin to address this issue, the impact of ablating L-FABP (LKO) or SCP-2/SCP-x (DKO) individually or both together (TKO) was examined in female mice. Biliary bile acid levels were decreased in LKO, DKO, and TKO mice; however, hepatic bile acid concentration was decreased in LKO mice only. In contrast, biliary phospholipid level was decreased only in TKO mice, while biliary cholesterol levels were unaltered regardless of phenotype. The loss of either or both genes increased hepatic expression of the major bile acid synthetic enzymes (CYP7A1 and/or CYP27A1). Loss of L-FABP and/or SCP-2/SCP-x genes significantly altered the molecular composition of biliary bile acids, but not the proportion of conjugated/unconjugated bile acids or overall bile acid hydrophobicity index. These data suggested that L-FABP was more important in hepatic retention of bile acids, while SCP-2/SCP-x more broadly affected biliary bile acid and phospholipid levels. PMID- 26541320 TI - Metastatic Colorectal Cancer: A Systematic Review of the Value of Current Therapies. AB - To evaluate, from a US payer perspective, the cost-effectiveness of treatment strategies for metastatic colorectal cancer (mCRC), we performed a systematic review of published cost-effectiveness analyses. We identified 14 papers that fulfilled our search criteria and revealed varying levels of value among current treatment strategies. Older agents such as 5-fluorouracil, irinotecan, and oxaliplatin provide high-value treatments. More modern agents targeting the EGFR or VEGF pathways, such as bevacizumab, cetuximab, and panitumumab, do not appear to be cost-effective treatments at their current costs. The analytical methods used within the papers varied widely, and this variation likely plays a significant role in the heterogeneity in incremental cost-effectiveness ratios. The cost-effectiveness of current treatment strategies for mCRC is highly variable. Drugs recently approved by the US Food and Drug Administration for mCRC are not cost-effective, and this is primarily driven by high drug costs. PMID- 26541321 TI - Safety and Efficacy of Radioembolization in Elderly (>= 70 Years) and Younger Patients With Unresectable Liver-Dominant Colorectal Cancer. AB - BACKGROUND: The effects of advancing age on clinical outcomes after radioembolization (RE) in patients with unresectable liver-dominant metastatic colorectal cancer (mCRC) are largely unknown. PATIENTS AND METHODS: This study was a retrospective analysis of 160 elderly (>= 70 years) and 446 younger (< 70 years) consecutive patients from 11 US centers who received RE using ytrrium-90 ((90)Y) resin microspheres ((90)Y radioembolization [(90)Y-RE]) between July 2002 and December 2011. A further analysis was conducted in 98 very elderly patients (>= 75 years). Statistical analyses of safety, tolerability, and overall survival were conducted. RESULTS: Mean ages (+/- standard deviation) in the younger (< 70 years), elderly (>= 70 years), and very elderly (>= 75 years) cohorts were 55.9 +/- 9.4 years, 77.2 +/- 4.8 years, and 80.2 +/- 3.8 years, respectively. Overall survival was similar between elderly and younger patients: 9.3 months (95% confidence interval [CI], 8.0-12.1) and 9.7 months (95% CI, 9.0-11.4) (P = .335). There were no differences between cohorts for any grade adverse events (P = .433) or grade 3+ events (P = .482). Analysis of patients >= 75 years and < 75 years confirmed similar overall survival (median, 9.3 months vs. 9.6 months, respectively; P = .987) and grade 3+ events (P = .398) or any adverse event (P = .158) within 90 days of RE. CONCLUSION: For patients with unresectable liver dominant mCRC who meet eligibility criteria for RE, (90)Y-RE microspheres appear to be effective and well-tolerated, regardless of age. Criteria for selecting patients for RE should not include age for exclusion from this potentially beneficial intervention. PMID- 26541322 TI - Hybrid lateral mass screw sublaminar wire construct: A salvage technique for posterior cervical fixation in pediatric spine surgery. AB - We present a novel salvage technique for pediatric subaxial cervical spine fusion in which lateral mass screw fixation was not possible due to anatomic constraints. The case presentation details a 4-year-old patient with C5-C6 flexion/distraction injury with bilateral jumped facets. Posterior cervical fixation was attempted; however, lateral mass fracture occurred during placement of screws. Using a wire-screw construct, an attempt was made to provide stable fixation. The patient was followed post-operatively for assessment of outcomes. After the patient had progressive kyphosis following initial closed reduction and external orthosis, internal reduction with fusion/fixation was performed. Lateral mass fracture occurred during placement of lateral mass screws. After placement of a sub-laminar wire-lateral mass screw construct, intra-operative evaluation determined stability. Post-operatively, the procedure resulted in stable fixation with evidence of bony fusion on follow-up. Pediatric subaxial cervical spine instrumentation provides rigid fixation however is technically difficult due to anatomic and instrumentation related constraints. In the presented patient, the wire-screw construct resulted in stable fixation and bony fusion on follow-up. A modified sublaminar wire-lateral mass screw construct is an example of a salvage technique that provides immediate stability in the event of instrumentation related lateral mass fracture. PMID- 26541323 TI - Asymptomatic progressive multifocal leukoencephalopathy during natalizumab therapy with treatment. AB - We report a case of asymptomatic progressive multifocal leukoencephalopathy (PML) detected on regular MRI screening in a 40-year-old patient with subsequent benign course with 12 months follow-up. The patient had a history of aggressive inflammatory multiple sclerosis, prior mitoxantrone therapy, Stratify John Cunningham Virus test positivity (Quest Diagnostics, Madison, NJ, USA), and 5 years of natalizumab monotherapy. The initial MRI detection of PML was both atypical and subtle. Early diagnosis and intervention, and pre-emptive treatment for immune reconstitution inflammatory syndrome with high dose steroids, as well as empirical mirtazapine and mefloquine, were associated with a benign PML disease course and outcome. PMID- 26541324 TI - Spontaneous acute subdural hematoma: A rare presentation of a dural intracranial fistula. AB - Dural arteriovenous fistulas are acquired lesions between the meningeal arteries and their associated draining veins. They may have highly variable clinical presentations and evolution, from severe neurological deficit to no or trivial symptoms. Intracranial hemorrhage occurs in less than 24% of all dural fistulas, and the bleeding is usually subarachnoid, more infrequently intracerebral, and rarely in the subdural space. Here, we present a rare case of a patient who presented with a subdural spontaneous hemorrhage. After investigation by cerebral angiography, the diagnosis of a dural arteriovenous fistula was made. The patient underwent uneventful endovascular treatment. As there are with only a few reports in the literature of such a presentation, we present this patient and perform a brief review of the literature. PMID- 26541325 TI - Reproducibility between messenger RNA real-time polymerase chain reaction and messenger RNA in situ hybridization in oropharyngeal squamous cell carcinoma patients--reply. PMID- 26541326 TI - Prognostic significance of PD-L1 and PD-L2 in breast cancer. AB - PD-L1 and PD-L2 constitute an important antitumor immune response. In breast cancer, their prognostic value is still to be defined. In this study, we investigate the correlation between PD-L1 and PD-L2 protein expressions with clinical and pathologic features and disease-free survival and overall survival. To assess PD-L1 and PD-L2 expressions, we conducted immunohistochemistry studies using a breast cancer tissue microarray encompassing a total of 192 breast cancer cases, stages I, II, and III, with detailed clinical and outcome data. PD-L1 expression was present in 56.6% (107/189), and PD-L2 expression was identified in 50.8% (97/191) of breast cancer cases. Younger age at diagnosis, lymph node positivity, negative estrogen receptor, and recurrence at distant sites were all associated with both PD-L1 and PD-L2 expressions. The presence of larger tumors was associated only with PD-L1 expression. In our study, PD-L1 expression was significantly associated with better overall survival (P = .04) in breast cancer patients. Despite its association with poor clinical and pathologic features, PD L1 expression emerges as a positive prognostic biomarker in breast cancer. This survival result might be due to the presence of a strong antitumor immune response leading to PD-L1 expression. PMID- 26541327 TI - Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts. AB - BACKGROUND: Acute liver failure (ALF) in infancy and childhood is a life threatening emergency and in about 50% the etiology remains unknown. Recently biallelic mutations in NBAS were identified as a new molecular cause of ALF with onset in infancy, leading to recurrent acute liver failure (RALF). METHODS: The phenotype and medical history of 14 individuals with NBAS deficiency was studied in detail and functional studies were performed on patients' fibroblasts. RESULTS: The phenotypic spectrum of NBAS deficiency ranges from isolated RALF to a multisystemic disease with short stature, skeletal dysplasia, immunological abnormalities, optic atrophy, and normal motor and cognitive development resembling SOPH syndrome. Liver crises are triggered by febrile infections; they become less frequent with age but are not restricted to childhood. Complete recovery is typical, but ALF crises can be fatal. Antipyretic therapy and induction of anabolism including glucose and parenteral lipids effectively ameliorates the course of liver crises. Patients' fibroblasts showed an increased sensitivity to high temperature at protein and functional level and a disturbed tethering of vesicles, pointing at a defect of intracellular transport between the endoplasmic reticulum and Golgi. CONCLUSIONS: Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes. PMID- 26541328 TI - Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota. AB - PURPOSE: To investigate the effect of virgin olive oil phenolic compounds (PC) alone or in combination with thyme PC on blood lipid profile from hypercholesterolemic humans, and whether the changes generated are related with changes in gut microbiota populations and activities. METHODS: A randomized, controlled, double-blind, crossover human trial (n = 12) was carried out. Participants ingested 25 mL/day for 3 weeks, preceded by 2-week washout periods, three raw virgin olive oils differing in the concentration and origin of PC: (1) a virgin olive oil (OO) naturally containing 80 mg PC/kg, (VOO), (2) a PC enriched virgin olive oil containing 500 mg PC/kg, from OO (FVOO), and (3) a PC enriched virgin olive oil containing a mixture of 500 mg PC/kg from OO and thyme, 1:1 (FVOOT). Blood lipid values and faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites were analysed. RESULTS: FVOOT decreased seric ox LDL concentrations compared with pre-FVOOT, and increased numbers of bifidobacteria and the levels of the phenolic metabolite protocatechuic acid compared to VOO (P < 0.05). FVOO did not lead to changes in blood lipid profile nor quantitative changes in the microbial populations analysed, but increased the coprostanone compared to FVOOT (P < 0.05), and the levels of the faecal hydroxytyrosol and dihydroxyphenylacetic acids, compared with pre-intervention values and to VOO, respectively (P < 0.05). CONCLUSION: The ingestion of a PC enriched virgin olive oil, containing a mixture of olive oil and thyme PC for 3 weeks, decreases blood ox-LDL in hypercholesterolemic humans. This cardio protective effect could be mediated by the increases in populations of bifidobacteria together with increases in PC microbial metabolites with antioxidant activities. PMID- 26541330 TI - Differential modulation of the discriminative stimulus effects of methamphetamine and cocaine by alprazolam and oxazepam in male and female rats. AB - Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effects of methamphetamine and cocaine in both male and female rats. Rats were trained to discriminate methamphetamine (1.0 mg/kg, ip) or cocaine (10 mg/kg, ip) from saline using a two-lever operant, food reinforced, drug discrimination design. Pretreatment with oxazepam (5, 10 and 20 mg/kg, ip) significantly attenuated methamphetamine discrimination in both male and female rats. In contrast, however, the high dose of alprazolam (4 mg/kg, ip) actually augmented the subjective effects of lower doses of methamphetamine (0.125 and 0.25 mg/kg, ip). Oxazepam produced similar effects on the subjective effects of cocaine as with methamphetamine, significantly reducing cocaine discrimination in both male and female rats. However, neither the high nor low dose of alprazolam (2 and 4 mg/kg, ip) produced any apparent effect on cocaine discrimination. Finally, while similar results were observed in both male and female rats across these experiments, methamphetamine and cocaine discrimination were more sensitive to oxazepam in female subjects. The results of these experiments suggest that alprazolam and oxazepam can differentially affect the subjective effects of methamphetamine and cocaine. These results also demonstrate that alprazolam can differentially affect the discriminative stimulus effects of methamphetamine and cocaine. PMID- 26541329 TI - Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex. AB - Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown. Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea. In the present study, we assessed whether inhibiting the primary endocannabinoid hydrolytic enzymes in the VIC reduces acute lithium chloride (LiCl)-induced conditioned gaping, a rat model of nausea. We also quantified endocannabinoid levels during an episode of nausea, and assessed VIC neuronal activation using the marker, c-Fos. Local inhibition of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of 2-arachidonylglycerol (2-AG), reduced acute nausea through a CB1 receptor mechanism, whereas inhibition of fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of anandamide (AEA), was without effect. Levels of 2 AG were also selectively elevated in the VIC during an episode of nausea. Inhibition of MAGL robustly increased 2-AG in the VIC, while FAAH inhibition had no effect on AEA. Finally, we demonstrated that inhibition of MAGL reduced VIC Fos immunoreactivity in response to LiCl treatment. Taken together, these findings provide compelling evidence that acute nausea selectively increases 2-AG in the VIC, and suggests that 2-AG signaling within the VIC regulates nausea by reducing neuronal activity in this forebrain region. PMID- 26541331 TI - Effect of high pH on growth of Synechocystis sp. PCC 6803 cultures and their contamination by golden algae (Poterioochromonas sp.). AB - Culturing cyanobacteria in a highly alkaline environment is a possible strategy for controlling contamination by other organisms. Synechocystis PCC 6803 cells were grown in continuous cultures to assess their growth performance at different pH values. Light conversion efficiency linearly decreased with the increase in pH and ranged between 12.5 % (PAR) at pH 7.5 (optimal) and decreased to 8.9 % at pH 11.0. Photosynthetic activity, assessed by measuring both chlorophyll fluorescence and photosynthesis rate, was not much affected going from pH 7.5 to 11.0, while productivity, growth yield, and biomass yield on light energy declined by 32, 28, and 26 % respectively at pH 11.0. Biochemical composition of the biomass did not change much within pH 7 and 10, while when grown at pH 11.0, carbohydrate content increased by 33 % while lipid content decreased by about the same amount. Protein content remained almost constant (average 65.8 % of dry weight). Cultures maintained at pH above 11.0 could grow free of contaminants (protozoa and other competing microalgae belonging to the species of Poterioochromonas). PMID- 26541332 TI - FudC, a protein primarily responsible for furfural detoxification in Corynebacterium glutamicum. AB - Lignocellulosic hydrolysates contain compounds that inhibit microbial growth and fermentation, thereby decreasing the productivity of biofuel and biochemical production. In particular, the heterocyclic aldehyde furfural is one of the most toxic compounds found in these hydrolysates. We previously demonstrated that Corynebacterium glutamicum converts furfural into the less toxic compounds furfuryl alcohol and 2-furoic acid. To date, however, the genes involved in these oxidation and reduction reactions have not been identified in the C. glutamicum genome. Here, we show that Cgl0331 (designated FudC) is mainly responsible for the reduction of furfural into furfuryl alcohol in C. glutamicum. Deletion of the gene encoding FudC markedly diminished the in vivo reduction of furfural to furfuryl alcohol. Purified His-tagged FudC protein from Escherichia coli was also shown to convert furfural into furfuryl alcohol in an in vitro reaction utilizing NADPH, but not NADH, as a cofactor. Kinetic measurements demonstrated that FudC has a high affinity for furfural but has a narrow substrate range for other aldehydes compared to the protein responsible for furfural reduction in E. coli. PMID- 26541333 TI - Continuous fungal treatment of non-sterile veterinary hospital effluent: pharmaceuticals removal and microbial community assessment. AB - Source point treatment of effluents with a high load of pharmaceutical active compounds (PhACs), such as hospital wastewater, is a matter of discussion among the scientific community. Fungal treatments have been reported to be successful in degrading this type of pollutants and, therefore, the white-rot fungus Trametes versicolor was applied for the removal of PhACs from veterinary hospital wastewater. Sixty-six percent removal was achieved in a non-sterile batch bioreactor inoculated with T. versicolor pellets. On the other hand, the study of microbial communities by means of DGGE and phylogenetic analyses led us to identify some microbial interactions and helped us moving to a continuous process. PhAC removal efficiency achieved in the fungal treatment operated in non sterile continuous mode was 44 % after adjusting the C/N ratio with respect to the previously calculated one for sterile treatments. Fungal and bacterial communities in the continuous bioreactors were monitored as well. PMID- 26541335 TI - Characterization and application of a common epitope recognized by a broad spectrum C4 monoclonal antibody against capsid proteins of plant potyviruses. AB - A broad-spectrum monoclonal antibody (C4 MAb) against the capsid proteins (CPs) of plant potyviruses has been generated in previous studies. To clarify which epitope is recognized by this MAb, epitope mapping was performed via phage display library screening and amino acid substitution analysis. Subsequently, a 12-residue epitope in the core region of potyvirus CPs was identified and termed the C4 epitope (WxMMDGxxQxxY/F). This epitope contains tryptophan and tyrosine residues that are crucial for reacting with C4 MAb. The CP of Odontoglossum ringspot tobamovirus (ORSV) separately fused with the C4 epitope of Konjak mosaic potyvirus (KoMV), Zantedeschia mild mosaic potyvirus (ZaMMV), or Dasheen mosaic potyvirus (DsMV) was expressed in a bacterial system and purified. The results of indirect ELISA and Western blotting demonstrated that the C4 epitope of KoMV (Ko) fused to ORSV CP showed the strongest binding affinity to C4 MAb among the three viral epitope tags examined. The binding affinity between Ko tag (WTMMDGEEQIEY) and C4 MAb was determined. To examine the applicability of the Ko tag in planta, GFP and ORSV CP were transiently expressed in Nicotiana benthamiana, and both Ko tagged proteins were specifically detected using C4 MAb. The Ko tag did not affect the silencing suppressor function of Tomato bushy stunt tombusvirus P19 in N. benthamiana. Furthermore, Ko-tagged EGFP could be successfully expressed, specifically detected and subsequently immunoprecipitated using C4 MAb in a mammalian cell system. Thus, the present study identified a common C4 epitope of potyviruses recognized by the broad-spectrum C4 and PTY 1 MAbs, and the results indicated that the newly designed Ko tag is suitable for application in bacterial, plant, and mammalian cell systems. PMID- 26541334 TI - Biotechnological aspects of ZnO nanoparticles: overview on synthesis and its applications. AB - The physicochemical methods of the synthesis of zinc nanoparticles (ZnO NPs) and some detailed studies on ZnO toxicity mechanism and biokinetics have been reported. However, some of these physical and chemical methods of synthesis are expensive and can also have toxic substances absorbed onto them. Hence, eco friendly synthesis of nanoparticles due to their easier process, cheaper availability, and high stability is dominating new research. In particular, ZnO NPs which are now being synthesized through major biological systems involved in this are bacteria, fungi, and plant extracts; this has increased studies in various applications in the biological field. In this review, we have elaborated on various natural source-mediated syntheses of ZnO NPs and their role in various biological activities like antimicrobial, anticandidal, larvicidal, cytotoxic, and photocatalytic activities. Apart from these applications, ZnO NPs are also reported to help to prevent dust formation, for several years, on oil paintings. PMID- 26541336 TI - Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children. AB - PURPOSE: Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. PATIENTS AND METHODS: Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9 196.6 months). RESULTS: Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. CONCLUSION: Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations. PMID- 26541337 TI - Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans. AB - Myopathies are heterogeneous disorders characterized clinically by weakness and hypotonia, usually in the absence of gross dystrophic changes. Mitochondrial dysfunction is a frequent cause of myopathy. We report a simplex case born to consanguineous parents who presented with muscle weakness, lactic acidosis, and muscle changes suggestive of mitochondrial dysfunction. Combined autozygome and exome analysis revealed a missense variant in the SLC25A42 gene, which encodes an inner mitochondrial membrane protein that imports coenzyme A into the mitochondrial matrix. Zebrafish slc25a42 knockdown morphants display severe muscle disorganization and weakness. Importantly, these features are rescued by normal human SLC25A42 RNA, but not by RNA harboring the patient's variant. Our data support a potentially causal link between SLC25A42 mutation and mitochondrial myopathy in humans. PMID- 26541339 TI - Kayser-Fleischer rings or bile pigment rings? PMID- 26541338 TI - Divine Interventions: Faith-Based Approaches to Health Promotion Programs for Latinos. AB - Few interventions have used faith-based approaches in health promotion programs among US Latinos, a notably religious population. This article explores the perceptions of church leaders, promotoras, and program participants on the Catholic religious context and content of a community-based intervention addressing physical activity, nutrition, and stress management for Chicago Latinas aged 50+. Nineteen in-depth interviews were conducted. Viewed as trustworthy, natural, and authentic, the church setting nurtured community bonds. Moreover, the program's religious content encouraged Latinas to feel motivated, connected, and engaged with the program in meaningful ways. Overall, faith-based health promotion programs offer a promising approach for Latino-centered interventions. PMID- 26541340 TI - Short sleep duration of overweight and obese patients with erosive esophagitis and gastritis. PMID- 26541341 TI - Differences in intestinal metaplasia in Barrett's esophagus patients in an ethnically diverse south London population. AB - Barrett's esophagus (BE) is the replacement of any portion of the normal distal squamous epithelial mucosa by metaplastic columnar epithelium and is the only known precursor for esophageal adenocarcinoma. We undertook a study to identify ethnic differences for the presence of intestinal metaplasia (IM) in BE in patients in an ethnically diverse south London population. Retrospective analysis was done using the endoscopy database of St George's Hospital NHS Trust, which serves a large ethnically diverse London population. Gastroscopy records between 2009 and 2012 were retrieved, and patients with an endoscopic diagnosis of BE were identified. Patients of Indian subcontinent Asian origin (ISCA) were further identified. The presence of IM was retrieved from hospital pathology databases and was the primary outcome measured. Multivariate logistic regression analysis was performed to determine the odds of having IM by ethnic origin. ISCAs were 70% less likely to have IM compared to non-ISCAs (OR 0.32, 95% CI: 0.16-0.61, p = 0.001). This is the first study to identify differences in histological findings in ISCAs with BE living in the UK. Our findings may be useful for the future risk stratification of BE patients. Identification of environmental factors responsible for this difference would be of great therapeutic value. PMID- 26541342 TI - Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection? AB - Despite 30 years of its discovery, the ideal therapeutic regimen against Helicobacter pylori is still evasive. Clarithromycin-based standard triple therapy which has been considered the first line empirical therapy has been failing in many parts of the world, due to rising resistance against Clarithromycin, forcing the use of alternate regimens. In this context, we studied the local antibiotic resistance patterns against H. pylori and its impact on standard triple therapy in our region. All patients undergoing diagnostic upper endoscopy during the study period and detected to be positive for rapid urease test (RUT) underwent cultures of gastric mucosal specimens and had their antibiotic resistance patterns mapped out. Standard triple therapy was administered to those tested positive for H. pylori by RUT and eradication rates checked by urea breath test 4 weeks after the completion of treatment. Eradication rates with Clarithromycin-based standard triple therapy were suboptimal with a success of only (71.28%). H. pylori culture and antibiotic susceptibility studies showed high resistance to Clarithromycin (21.2%), Metronidazole (78.1%), and Levofloxacin (15%). However, the resistance to Amoxicillin (2.9%), Tetracycline (0%), and Rifabutin (4.5%) were low. Standard triple therapy is failing in our region due to high Clarithromycin resistance. We need to abandon empirical and blind triple therapy without post-treatment testing and devise alternate effective treatment strategies against H. pylori based on the local resistance patterns observed. PMID- 26541343 TI - Involvement of membrane skeletal molecules in the Schmidt-Lanterman incisure in Schwann cells. AB - Membrane skeletal networks form a two-dimensional lattice structure beneath erythrocyte membranes. 4.1R-MPP (membrane palmitoylated protein) 1-glycophorin C is one of the basic molecular complexes of the membrane skeleton. An analogous molecular complex, 4.1G-MPP6-cell adhesion molecule 4 (CADM4), is incorporated into the Schmidt-Lanterman incisure (SLI), a truncated cone shape in the myelin internode that is a specific feature of myelinated nerve fibers formed in Schwann cells in the peripheral nervous system. In this review, the dynamic structure of peripheral nerve fibers under stretching conditions is demonstrated using in vivo cryotechnique. The structures of nerve fibers had a beaded appearance, and the heights of SLI circular-truncated cones increased at the narrow sites of nerve fibers under the stretched condition. The height of SLI-truncated cones was lower in 4.1G-deficient nerve fibers than in wild-type nerve fibers. 4.1G was essential for the molecular targeting of MPP6 and CADM4 in SLI. The signal transduction protein, Src, was also involved in the 4.1G-MPP6-CADM4 molecular complex. The phosphorylation of Src was altered by the deletion of 4.1G. Thus, we herein demonstrate a membrane skeletal molecular complex in SLI that has potential roles in the regulation of adhesion and signal transduction as well as in structural stability in Schwann cells. PMID- 26541344 TI - A J-shaped relationship between caloric intake and survival in critically ill patients. AB - BACKGROUND: There is much controversy around the optimal caloric intake in intensive care unit (ICU) patients, based on the diverging results of prospective studies. Therefore, we assessed the presence of an association between caloric intake and outcome in a large cohort included in the Glucontrol study. METHODS: Patients (n = 1004) were divided into four quartiles (q1-q4) according to the daily caloric intake (n = 251/quartile). ICU, hospital and 28-day mortality and the length of stay (LOS) in ICU and in the hospital were compared between each quartile, before and after adjustment in case of differences in baseline characteristics. RESULTS: Caloric intake averaged 0.5 +/- 0.6 (q1), 3.0 +/- 0.7 (q2), 13.4 +/- 5.1 (q3) and 32.4 +/- 8.5 (q4) kcal/kg/day (p < 0.001 between quartiles). Comparisons among quartiles revealed that ICU, hospital and 28-day mortality were lower in q2 than in the other quartiles. ICU and hospital LOS were lower in q1 and q2. After adjustment for age, type of admission and severity scores, hospital mortality was lower in q2 than in the other quartiles, and LOS was lower in q1and q2 than in q3-q4. CONCLUSIONS: In this large and heterogeneous cohort of ICU short stayers, a J-shaped relationship between the amount of calories provided and outcome was found. These hypothesis generating findings are consistent with the concept of improved clinical outcome by early energy restriction. Trial registration#: ClinicalTrials.gov# NCT00107601, EUDRA-CT Number: 200400391440. PMID- 26541345 TI - Will next-generation agents deliver on the promise of epigenetic hypomethylation therapy? PMID- 26541346 TI - Alzheimer's disease in the 100 years since Alzheimer's death. PMID- 26541347 TI - The EU-project United4Health: User-centred design of an information system for a Norwegian telemedicine service. AB - INTRODUCTION: Organizational changes of health care services in Norway brought to light a need for new clinical pathways. This study presents the design and evaluation of an information system for a new telemedicine service for chronic obstructive pulmonary disease patients after hospital discharge. METHODS: A user centred design approach was employed composed of a workshop with end-users, two user tests and a field trial. For data collection, qualitative methods such as observations, semi-structured interviews and a questionnaire were used. RESULTS: User workshop's outcome informed the implementation of the system initial prototype, evaluated by end-users in a usability laboratory. Several usability and functionality issues were identified and solved, such as the interface between the initial colour scheme and the triage colours. Iterative refinements were made and a second user evaluation showed that the main issues were solved. The responses to a questionnaire presented a high score of user satisfaction. In the final phase, a field trial showed satisfactory use of the system. DISCUSSION: This study showed how the target end-users groups were actively involved in identifying the needs, suggestions and preferences. These aspects were addressed in the development of an information system through a user-centred design process. The process efficiently enabled users to give feedback about design and functionality. Continuous refinement of the system was the key to full development and suitability for the telemedicine service. This research was a result of the international cooperation between partners within the project United4Health, a part of the Seventh Framework Programme for Research of the European Union. PMID- 26541348 TI - Utility of Cardiac Troponin to Predict Drug Overdose Mortality. AB - Drug overdose is now the leading cause of injury-related mortality in the USA, but the prognostic utility of cardiac biomarkers is unknown. We investigated whether serum cardiac troponin I (cTnI) was associated with overdose mortality. This prospective observational cohort studied adults with suspected acute drug overdose at two university hospital emergency departments (ED) over 3 years. The endpoint was in-hospital mortality, which was used to determine test characteristics of initial/peak cTnI. There were 437 overdoses analyzed, of whom there were 20 (4.6 %) deaths. Mean initial cTnI was significantly associated with mortality (1.2 vs. 0.06 ng/mL, p < 0.001), and the ROC curve revealed excellent cTnI prediction of mortality (AUC 0.87, CI 0.76-0.98). Test characteristics for initial cTnI (90 % specificity, 99 % negative predictive value) were better than peak cTnI (88.2 % specificity, 99.2 % negative predictive value), and initial cTnI was normal in only one death out of the entire cohort (1/437, CI 0.1-1.4 %). Initial cTnI results were highly associated with drug overdose mortality. Future research should focus on high-risk overdose features to optimize strategies for utilization of cTnI as part of the routine ED evaluation for acute drug overdose. PMID- 26541349 TI - Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor Construct. AB - Renovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 MUg/kg), a matching concentration of unconjugated VEGF (18.65 MUg/kg), ELP alone (100 MUg/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function. PMID- 26541350 TI - Effect of Short-Term Steroid Therapy on Early Recurrence During the Blanking Period After Catheter Ablation of Atrial Fibrillation. AB - BACKGROUND: Early recurrence (ER) of atrial tachyarrhythmias during the first 3 months (blanking period) after atrial fibrillation ablation can be highly symptomatic, often requiring emergency treatment. Short-term steroid therapy may suppress ER during the blanking period. METHODS AND RESULTS: We prospectively enrolled 138 patients who were randomly assigned to 2 groups (steroid group and control group). An intravenous bolus of 0.5 mg/kg of methylprednisolone for 2 days followed by 12 mg daily of oral methylprednisolone for 4 days was given to the steroid group patients. The primary end point was ER during the blanking period (3 months post ablation). During the blanking period, 51 of the 138 (37.0%) patients experienced ER after atrial fibrillation ablation. The steroid group had a lower rate of ER than the control group (15/64 [23.4%] versus 36/74 [48.6%], P=0.003). There was no difference between the 2 groups about late recurrence during a 24-month follow-up (log-rank test, P=0.918). In a multivariate analysis, short-term steroid therapy was independently associated with a lower rate of ER during the blanking period (adjusted OR, 0.45; 95% confidence interval, 0.25-0.83; P=0.01). CONCLUSIONS: Periprocedural short-term moderate intensity steroid therapy reduces ER (~3 months) after catheter ablation of atrial fibrillation. It is not effective in preventing late (3~24 m) atrial fibrillation recurrence. CLINICAL TRIAL REGISTRATION: URL: www.who.int/ictrp; Unique identifier: KCT0000107. PMID- 26541351 TI - Omega-3 Fatty Acids and Cholesterol Have a Main Role in Antidepression Diet of Iranian Traditional Medicine. AB - Depression is one of the major health problems of our world. Recent studies have revealed the relationship between diet and depression. In Iranian traditional medicine, there is a therapeutic diet that is recommended in melancholic diseases like depression. One of the main components of this diet is meat. Meats are divided into 2 groups: recommended and abstinent. The aim of this study was to clarify the logic of this diet through comparing nutritional elements of the 2 groups with each other. For this purpose, prominent books on Iranian traditional medicine were searched for abstinent and recommended meats traditionally prescribed for depressed patients. The results of each group were compared with the other by using Mann-Whitney Test (SPSS version 16). The results showed that recommended meats contain higher amounts of polyunsaturated fatty acids ( P = .01) especially omega-3 ( P = .03). Both groups contain high amounts of cholesterol. Iranian traditional medicine recommends consumption of meats that contains cholesterol with omega-3 fatty acids in depression. PMID- 26541352 TI - Co-occurrence of eosinophilic esophagitis and potential/probable celiac disease in an adult cohort: a possible association with implications for clinical practice. AB - We describe an adult cohort with eosinophilic esophagitis (EoE) and evidence of celiac disease (CD), propose a change in diagnostic practice to better characterize these conditions, and hypothesize new directions for research. Pediatric studies postulate association between gluten sensitivity and EoE. However, few publications describe the prevalence, detection, or therapeutic and pathophysiologic implications of such association in adults. Retrospective chart review was done on patients diagnosed with EoE from 2009 to 2010 at University of Utah Hospitals and Clinics. Data included sex, age, presentation, duodenal pathology, tissue transglutaminase immunoglobulin A antibody (TTG) positivity, human leukocyte antigen (HLA) type (when indicated), and gross and microscopic Esophagogastroduodenoscopy (EGD) findings. Duodenal biopsy, TTG results, and HLA type were correlated. Endoscopy was repeated after gluten-free diet. Forty-four of 75 patients were followed in EoE specialty clinic with duodenal biopsy and TTG testing per protocol. Six EoE patients had potential or probable CD. No sex or age differences were noted between those with findings of CD and EoE and those with EoE alone. Six patients with findings of CD and EoE followed gluten-free diet. Five underwent repeat endoscopy. Three had resolution of esophageal eosinophilia. Potential or probable CD was commonly found in adults with EoE. Diagnosis of CD may be challenging due to nonspecific symptoms and insufficient duodenal biopsy and serologic testing. Furthermore, gluten-free diet resolved EoE findings in some patients, suggesting possible shared pathophysiology in some cases of EoE and CD. TTG testing and adequate duodenal biopsy may further direct clinical care for EoE patients, and studies are needed to elucidate mechanisms linking EoE and CD. PMID- 26541354 TI - Design, Synthesis, and Biological Evaluation of Quercetagetin Analogues as JNK1 Inhibitors. AB - The recent discovery of c-Jun NH2-terminal kinase JNK1 suppression by natural quercetagetin (1) is a promising lead for the development of novel anticancer agents. Using both X-ray structure and docking analyses we predicted that 5' hydroxy- (2) and 5'-hydroxymethyl-quercetagetin (3) would inhibit JNK1 more actively than the parent compound 1. Notably, our drug design was based on the active enzyme-ligand complex as opposed to the enzyme's relatively open apo structure. In this paper we test our theoretical predictions, aided by docking model experiments, and report the first synthesis and biological evaluation of quercetagetin analogues 2 and 3. As calculated, both compounds strongly suppress JNK1 activity. The IC50 values were determined to be 3.4 MUM and 12.2 MUM, respectively, which shows that 2 surpasses the potency of the parent compound 1 (IC50 =4.6 MUM). Compound 2 was also shown to suppress matrix metalloproteinase-1 expression with high specificity after UV irradiation. PMID- 26541355 TI - Designing the Molybdopterin Core through Regioselective Coupling of Building Blocks. AB - Molybdopterin is an essential cofactor for all forms of life. The cofactor is composed of a pterin moiety appended to a dithiolene-functionalized pyran ring, and through the dithiolene moiety it binds metal ions. Different synthetic strategies for dithiolene-functionalized pyran precursors that have been designed and synthesized are discussed. These precursors also harbor 1,2-diketone or osone functionality that has been condensed with 1,2-diaminobenzene or other heterocycles resulting in several quinoxaline or pterin derivatives. Use of additives improves the regioselectivity of the complexes. The molecules have been characterized by (1)H and (13)C NMR and IR spectroscopies, as well as by mass spectrometry. In addition, several compounds have been crystallographically characterized. The geometries of the synthesized molecules are more planar than the geometry of the cofactor found in proteins. PMID- 26541358 TI - Synthetic Tet-inducible artificial microRNAs targeting beta-catenin or HIF-1alpha inhibit malignant phenotypes of bladder cancer cells T24 and 5637. AB - Ribonucleic acid interference (RNAi) based on microRNA (miRNA) may provide efficient and safe therapeutic opportunities. However, natural microRNAs can not easily be regulated and usually cause few phenotypic changes. Using the engineering principles of synthetic biology, we provided a novel and standard platform for the generation of tetracycline (Tet)-inducible vectors that express artificial microRNAs in a dosage-dependent manner. The vector generates a Pol II promoter-mediated artificial microRNA which was flanked by ribozyme sequences. In order to prove the utility of this platform, we chose beta-catenin and HIF-1alpha as the functional targets and used the bladder cancer cell lines 5637 and T24 as the test models. We found that the Tet-inducible artificial microRNAs can effectively silence the target genes and their downstream genes, and induce anti cancer effects in the two bladder cancer cell lines. These devices can inhibit proliferation, induce apoptosis, and suppress migration of the bladder cancer cell lines 5637 and T24. The Tet-inducible synthetic artificial microRNAs may represent a kind of novel therapeutic strategies for treating human bladder cancer. PMID- 26541359 TI - Neck fracture of the Exeter stem in 3 patients: A cause for concern? PMID- 26541361 TI - How Consistent are Publicly Reported Cytotoxicity Data? Large-Scale Statistical Analysis of the Concordance of Public Independent Cytotoxicity Measurements. AB - While increased attention is being paid to the impact of data quality in cell line sensitivity and toxicology modeling, to date, no systematic study has evaluated the comparability of independent cytotoxicity measurements on a large scale. Here, we estimate the experimental uncertainty of public cytotoxicity data from ChEMBL version 19. We applied stringent filtering criteria to assemble a curated data set comprised of pIC50 data for compound-cell line systems measured in independent laboratories. The estimated experimental uncertainty calculated was a mean unsigned error (MUE) value of 0.61-0.76, a median unsigned error (MedUE) value of 0.51-0.58, and a standard deviation of 0.76-1.00 pIC50 units. The experimental uncertainty (sigmaE) estimated from all pairs of cytotoxicity measurements with a DeltapIC50 value lower than 2.5 was found to be 0.59-0.77 pIC50 units, and thus 21-60% and 21-26% higher than that of pKi and pIC50 data for ligand-protein data (sigmaE =0.47-0.48 pKi units and sigmaE =0.57-0.61 pIC50 units, respectively). The estimated sigmaE value from the pairs of pIC50 values measured with metabolic assays was 0.98, whereas the sigmaE value was found to be 0.69 when using the 1388 pIC50 pairs measured using exactly the same experimental setup. The maximum achievable Pearson correlation coefficient (RPearsonmax.2) of in silico models trained on cytotoxicity data from different laboratories was estimated to be 0.51-0.85, which is considerably different from the value of 1 corresponding to perfect predictions, hinting at the maximum performance one can expect also from computational cytotoxicity predictions. The lowest concordance between pairs of measurements was found for the drugs paclitaxel, methotrexate, zidovudine, and docetaxel, and for the cell lines HepG2, NCI-H460, L1210, and CCRF-CEM, hinting at particular sensitivity of those systems to experimental setups. The highest concordance was estimated for the compound-cell line system HL-60-etoposide (sigmaE =0.70), whereas the lowest for L1210-methotrexate (sigmaE =1.68). We found that annotation errors are responsible for the high discordance observed for some pairs of measurements, pointing out the importance of data curation when automatically extracting cytotoxicity data from public databases. Likewise, these results highlight the importance of estimating compound cytotoxicity with assays providing complementary biological information (i.e., metabolic, clonogenic and assays based on cell membrane integrity), especially when the mechanism of action of test compounds is unknown. From this analysis, guidelines can be created on the reliability of cytotoxicity data from public databases, which could ultimately prove valuable for modeling purposes, and to guide reporting of data in the literature. PMID- 26541360 TI - Aberrant regulation of synchronous network activity by the attention deficit/hyperactivity disorder-associated human dopamine D4 receptor variant D4.7 in the prefrontal cortex. AB - KEY POINTS: The hD4.7 variant has been linked to attention-deficit/hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. We found that activation of hD4.7 induced over-suppression of glutamatergic excitatory network bursts and under-suppression of GABAergic inhibitory network bursts in the prefrontal cortex (PFC) circuitry. Methylphenidate, a psychostimulant drug used to treat ADHD, normalized the effects of hD4.7 on synchronous network bursts in PFC pyramidal neurons. The findings of the present study suggest that the aberrant regulation of PFC synchronous network activity by hD4.7 may underlie its involvement in ADHD. A unique feature of the human D4 receptor (hD4 R) gene is the existence of a large number of polymorphisms in exon 3 coding for the third intracellular loop, which consists of a variable number of tandem repeats. The hD4 R variants with long repeats have been linked to attention deficit/hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. Emerging evidence suggests that selective attention is controlled by the rhythmic synchronization in the prefrontal cortex (PFC) and its connected networks. In the present study, we examined the role of hD4 R variants in regulating PFC synchronous network activity. D4 R knockout mice with viral infection of hD4.4 or hD4.7 in the medial PFC were used. Whole-cell patch-clamp recordings were performed to examine the effects of activating hD4.x on the spontaneous large scale correlated activity in PFC pyramidal neurons. We found that, compared to the normal four-repeat variant hD4.4, the ADHD-linked variant hD4.7 induces more suppression of glutamatergic excitatory network bursts and less suppression of GABAergic inhibitory network bursts in the PFC circuitry. Methylphenidate, a psychostimulant drug used to treat ADHD, normalized the effects of hD4.7 on synchronous network bursts in PFC pyramidal neurons. These results reveal the differential effects of hD4 R variants on the integrated excitability of PFC circuits. It is suggested that the aberrant regulation of PFC network activity by hD4.7 may underlie its involvement in ADHD. The methylphenidate-induced normalization of synaptic circuitry regulation may contribute to its effectiveness in ADHD treatment. PMID- 26541364 TI - Education in Professionalism: The Radiologist as Beauty Queen. PMID- 26541363 TI - Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. AB - Several distinct graft-versus-host disease (GVHD)-related syndromes have been defined by the National Institutes of Health Consensus Conference. We enrolled a prospective cohort of 911 hematopoietic cell transplantation (HCT) recipients at 13 centers between March 2011 and May 2014 to evaluate 4 GVHD syndromes: late acute GVHD (aGVHD), chronic GVHD (cGVHD), bronchiolitis obliterans syndrome, and cutaneous sclerosis. The median age at HCT was 53.7 years. The majority of patients received a peripheral blood stem cell transplant (81%) following nonmyeloablative or reduced-intensity conditioning (55%). Pediatric age group and use of bone marrow and umbilical cord blood grafts were underrepresented in our cohort (<=11%). The cumulative incidence of late aGVHD (late onset and recurrent) was 10% at a median of 5.5 months post-HCT, that of cGVHD was 47% at a median of 7.4 months, that of bronchiolitis obliterans was 3% at a median of 12.2 months, and that of cutaneous sclerosis was 8% at a median onset of 14.0 months. Late aGVHD and bronchiolitis obliterans had particularly high nonrelapse mortality of 23% and 32%, respectively, by 2 years after diagnosis. The probability of late aGVHD- and cGVHD-free, relapse-free survival was 38% at 1 year post-HCT and 26% at 2 years post-HCT. This multicenter prospective study confirms the high rate of late aGVHD and cGVHD syndromes and supports the need for continuous close monitoring and development of more effective GVHD treatment strategies to improve HCT success. PMID- 26541366 TI - MRP1 and its role in anticancer drug resistance. AB - The phenomenon of multidrug resistance (MDR) in cancer is associated with the overexpression of the ATP-binding cassette (ABC) transporter proteins, including multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein. MRP1 plays an active role in protecting cells by its ability to efflux a vast array of drugs to sub-lethal levels. There has been much effort in elucidating the mechanisms of action, structure and substrates and substrate binding sites of MRP1 in the last decade. In this review, we detail our current understanding of MRP1, its clinical relevance and highlight the current environment in the search for MRP1 inhibitors. We also look at the capacity for the rapid intercellular transfer of MRP1 phenotype from spontaneously shed membrane vesicles known as microparticles and discuss the clinical and therapeutic significance of this in the context of cancer MDR. PMID- 26541365 TI - The Effect of Cranioplasty on Cerebral Hemodynamics as Measured by Perfusion Computed Tomography and Doppler Ultrasonography. AB - Cranioplasties are performed to protect the brain and correct cosmetic defects, but there is growing evidence that this procedure may result in neurological improvement. We prospectively studied cranioplasties performed at our hospital over a 5-year period. The National Institute of Health Stroke Scale and Barthel index were recorded prior to and within 72 h after the cranioplasty. A perfusion computed tomography (PCT) and transcranial Doppler sonography (TCDS) were performed prior to and 72 h after the surgery. For the PCT, regions irrigated by the anterior cerebral artery, the middle cerebral artery (MCA), the posterior cerebral artery, and the basal ganglia were selected, as well as the mean values for the hemisphere. The sonography was performed in the sitting and the supine position for the MCA and internal carotid. The velocities, pulsatility index, resistance index, and Lindegaard ratio (LR) were obtained, as well as a variation value for the LR (DeltaLR = LR sitting - LR supine). Fifty-four patients were included in the study. Of these, 23 (42.6%) patients presented with objective improvement. The mean cerebral blood flow of the defective side (m-CBF-d) increased from 101.86 to 117.17 mL/100 g/min (p = 0.064), and the m-CBF of the healthy side (m-CBF-h) increased from 128.14 to 145.73 mL/100 g/min (p = 0.028). With regard to the TCDS, the DeltaLR was greater on the defective side prior the surgery in those patients who showed improvement (1.295 vs. -0.714; p = 0.002). Cranioplasty resulted in clinical improvement in 40% of the patients, with an increase in the post-surgical CBF. The larger variations in the LR when the patient is moved from the sitting to the supine position might predict the clinical improvement. PMID- 26541367 TI - Enantioselective Preparation, Conformational Analysis and Absolute Configuration of Highly Substituted Aziridines. AB - The first example of organocatalytic aziridination reaction of alpha-substituted alpha,beta-unsaturated ketones is presented. The reaction was found to be highly enantio- and diastereoselective, yielding N-tosylated aziridines. Low-temperature nuclear magnetic resonance (NMR) spectra allowed for the determination of the N inversion barrier, that was found to be quite lower with respect to unsubstituted aziridines. A thorough conformational analysis supported by low-temperature NMR data allowed for the determination of the absolute configuration of the main stereoisomer by means of time-dependent Density Functional Theory simulation of the electronic circular dichroism spectra. PMID- 26541368 TI - Biomimetic Synthesis and Studies Toward Enantioselective Synthesis of Flindersial Alkaloids. PMID- 26541369 TI - Exoenzymes and metabolites related to the nematicidal effect of rhizobacteria on Xiphinema index Thorne & Allen. AB - AIMS: To identify enzymes and metabolites in the rhizobacteria filtrates that have a nematicidal effect on Xiphinema index and perform molecular characterization of the strains evaluated. METHODS AND RESULTS: A series of four bacteria selected for their nematicidal potential were considered for in vitro, biochemical and molecular studies. The direct effect of the bacterial filtrates was evaluated in vitro on X. index juveniles and adults. Hydrogen sulphide and hydrogen cyanide liberation and protease, chitinase, collagenase and lipase activity were verified in the strains. Up to five housekeeping genes and one ITS 16S-23S rRNA were analysed. All bacterial filtrates presented 54-100% mortality when evaluated during up to 72 h of nematode exposure. Strains presented protease activity; two of them (strains FB833T and FR203A) showed reliable collagenase and chitinase activities, respectively, and three of them showed strong lipolytic activity (FB833T, FR203A and FS213P). Strain Bacillus megaterium FB133M had no lipase activity and presented the lowest nematicidal effect. Bacillus amyloliquefaciens FR203A had the largest lethal effect. CONCLUSION: The rhizobacteria strains evaluated in this study possess nematicidal compounds, which may offer an interesting alternative for X. index control. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of exoenzymes and metabolites associated with nematicidal effect of rhizobacteria on X. index, which can be a possible alternative for control of this plant-parasitic nematode. PMID- 26541370 TI - Evaluation of DNA extraction kits and phylogenetic diversity of the porcine gastrointestinal tract based on Illumina sequencing of two hypervariable regions. AB - A robust DNA extraction method is important to identify the majority of microorganisms present in environmental microbial communities and to enable a consistent comparison between different studies. Here, 15 manual and four automated commercial DNA extraction kits were evaluated for their efficiency to extract DNA from porcine feces and ileal digesta samples. DNA yield, integrity, and purity varied among the different methods. Terminal restriction fragment length polymorphism (T-RFLP) and Illumina amplicon sequencing were used to characterize the diversity and composition of the microbial communities. We also compared phylogenetic profiles of two regions of the 16S rRNA gene, one of the most used region (V1-2) and the V5-6 region. A high correlation between community structures obtained by analyzing both regions was observed at genus and family level for ileum digesta and feces. Based on our findings, we want to recommend the FastDNA(TM) SPIN Kit for Soil (MP Biomedical) as a suitable kit for the analyses of porcine gastrointestinal tract samples. PMID- 26541371 TI - Innovative Strategy on Hydrogen Evolution Reaction Utilizing Activated Liquid Water. AB - Splitting water for hydrogen production using light, or electrical energy, is the most developed 'green technique'. For increasing efficiency in hydrogen production, currently, the most exciting and thriving strategies are focused on efficient and inexpensive catalysts. Here, we report an innovative idea for efficient hydrogen evolution reaction (HER) utilizing plasmon-activated liquid water with reduced hydrogen-bonded structure by hot electron transfer. This strategy is effective for all HERs in acidic, basic and neutral systems, photocatalytic system with a g-C3N4 (graphite carbon nitride) electrode, as well as in an inert system with an ITO (indium tin oxide) electrode. Compared to deionized water, the efficiency of HER increases by 48% based on activated water ex situ on a Pt electrode. Increase in energy efficiency from activated water is 18% at a specific current yield of -20 mA in situ on a nanoscale-granulated Au electrode. Moreover, the onset potential of -0.023 V vs RHE was very close to the thermodynamic potential of the HER (0 V). The measured current density at the corresponding overpotential for HER in an acidic system was higher than any data previously reported in the literature. This approach establishes a new vista in clean green energy production. PMID- 26541372 TI - Assessment of YouTube videos as a source of information on medication use in pregnancy. AB - BACKGROUND: When making decisions about medication use in pregnancy, women consult many information sources, including the Internet. The aim of this study was to assess the content of publicly accessible YouTube videos that discuss medication use in pregnancy. METHODS: Using 2023 distinct combinations of search terms related to medications and pregnancy, we extracted metadata from YouTube videos using a YouTube video Application Programming Interface. Relevant videos were defined as those with a medication search term and a pregnancy-related search term in either the video title or description. We viewed relevant videos and abstracted content from each video into a database. We documented whether videos implied each medication to be "safe" or "unsafe" in pregnancy and compared that assessment with the medication's Teratogen Information System (TERIS) rating. RESULTS: After viewing 651 videos, 314 videos with information about medication use in pregnancy were available for the final analyses. The majority of videos were from law firms (67%), television segments (10%), or physicians (8%). Selective serotonin reuptake inhibitors (SSRIs) were the most common medication class named (225 videos, 72%), and 88% of videos about SSRIs indicated that they were unsafe for use in pregnancy. However, the TERIS ratings for medication products in this class range from "unlikely" to "minimal" teratogenic risk. CONCLUSION: For the majority of medications, current YouTube video content does not adequately reflect what is known about the safety of their use in pregnancy and should be interpreted cautiously. However, YouTube could serve as a platform for communicating evidence-based medication safety information. PMID- 26541373 TI - Self-affirmation activates brain systems associated with self-related processing and reward and is reinforced by future orientation. AB - Self-affirmation theory posits that people are motivated to maintain a positive self-view and that threats to perceived self-competence are met with resistance. When threatened, self-affirmations can restore self-competence by allowing individuals to reflect on sources of self-worth, such as core values. Many questions exist, however, about the underlying mechanisms associated with self affirmation. We examined the neural mechanisms of self-affirmation with a task developed for use in a functional magnetic resonance imaging environment. Results of a region of interest analysis demonstrated that participants who were affirmed (compared with unaffirmed participants) showed increased activity in key regions of the brain's self-processing (medial prefrontal cortex + posterior cingulate cortex) and valuation (ventral striatum + ventral medial prefrontal cortex) systems when reflecting on future-oriented core values (compared with everyday activities). Furthermore, this neural activity went on to predict changes in sedentary behavior consistent with successful affirmation in response to a separate physical activity intervention. These results highlight neural processes associated with successful self-affirmation, and further suggest that key pathways may be amplified in conjunction with prospection. PMID- 26541374 TI - Modeling sequence and quasi-uniform assumption in computational neurostimulation. AB - Computational neurostimulation aims to develop mathematical constructs that link the application of neuromodulation with changes in behavior and cognition. This process is critical but daunting for technical challenges and scientific unknowns. The overarching goal of this review is to address how this complex task can be made tractable. We describe a framework of sequential modeling steps to achieve this: (1) current flow models, (2) cell polarization models, (3) network and information processing models, and (4) models of the neuroscientific correlates of behavior. Each step is explained with a specific emphasis on the assumptions underpinning underlying sequential implementation. We explain the further implementation of the quasi-uniform assumption to overcome technical limitations and unknowns. We specifically focus on examples in electrical stimulation, such as transcranial direct current stimulation. Our approach and conclusions are broadly applied to immediate and ongoing efforts to deploy computational neurostimulation. PMID- 26541375 TI - Multilevel computational models for predicting the cellular effects of noninvasive brain stimulation. AB - Since 2000, there has been rapid acceleration in the use of tDCS in both clinical and cognitive neuroscience research, encouraged by the simplicity of the technique (two electrodes and a battery powered stimulator) and the perception that tDCS protocols can be simply designed by placing the anode over the cortex to "excite," and the cathode over cortex to "inhibit." A specific and predictive understanding of tDCS needs experimental data to be placed into a quantitative framework. Biologically constrained computational models provide a useful framework within which to interpret results from empirical studies and generate novel, testable hypotheses. Although not without caveats, computational models provide a tool for exploring cognitive and brain processes, are amenable to quantitative analysis, and can inspire novel empirical work that might be difficult to intuit simply by examining experimental results. We approach modeling the effects of tDCS on neurons from multiple levels: modeling the electric field distribution, modeling single-compartment effects, and finally with multicompartment neuron models. PMID- 26541376 TI - Experiments and models of cortical oscillations as a target for noninvasive brain stimulation. AB - Noninvasive brain stimulation is attracting substantial attention due to its potential for safe and effective modulation of brain network dynamics. Promising applications include cognitive enhancement and treatment of disorders of the central nervous system. Recently, targeting of cortical oscillations by brain stimulation with periodic electromagnetic waveforms has emerged as a particularly appealing approach for understanding the causal role of cortical oscillations in human cognition and behavior. Two main approaches exist: repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS); rTMS is more widely used as a research and clinical tool but only recently has it been suggested to selectively engage frequency-matched cortical oscillations. In contrast, tACS is an offspring of transcranial direct current stimulation and has been introduced with the specific aim of engaging cortical oscillations. One of the main lessons that the field of noninvasive brain stimulation has learned over the last few years is that without a mechanistic understanding of how stimulation engages neuronal circuits, little progress can be made toward the rational design of individualized, adaptive stimulation treatments. Computer simulations of cellular and network models from the field of computational neuroscience are a key tool to gain such a mechanistic understanding. However, the insights gained from such modeling strategies can only be fully leveraged when used in tight conjunction with experimental approaches in both human and animal model studies. Here, I provide an in-depth review of the pioneering experimental and computational studies that together provide the basis for understanding how periodic noninvasive brain stimulation targets cortical oscillations to enable the rational design of brain stimulation treatments for disorders associated with specific deficits in cortical oscillations. PMID- 26541377 TI - Understanding the nonlinear physiological and behavioral effects of tDCS through computational neurostimulation. AB - Despite the success of noninvasive brain stimulation (NIBS), the mechanism of action through which different stimulation techniques interact with information processing in targeted neural circuits largely remains unknown. Applying neurostimulation in silico to computational models with biophysical plausibility provides one route to interrogate the possible mechanisms through which stimulation interacts with neural circuits, and generate predictions about the resultant behavior. Here, we address the recent observation that the physiological and behavioral effects of transcranial direct current stimulation (tDCS) might be nonlinear with regard to stimulation intensity or duration. We simulate neurostimulation in an established, biophysically informed neural network attractor model that generates simple behavioral choices and thus allows for assessing the impact of stimulation on both neural dynamics and behavior. We demonstrate that nonlinear effects of stimulation intensity on the accuracy and decision time of the model can arise from a limit on the integration rate of the network, nonlinear effects of stimulation on neural firing rates before the onset of the stimulus, and the inhibitory effect of hyperpolarizing stimulation on pyramidal neurons. We thus present a detailed modeling treatment of nonlinear tDCS effects during a behavioral task, and provide detailed hypotheses about the neural causes that lead to observed nonlinear behavioral effects during stimulation. This framework can provide a blueprint for future work on the neural and behavioral consequences of NIBS in health and disease. PMID- 26541378 TI - Modeling TMS-induced I-waves in human motor cortex. AB - Despite many years of research, it is still unknown how exactly transcranial magnetic stimulation activates cortical circuits. A recent computational model by Rusu et al. (2014) has attempted to shed light on potential underlying mechanisms and has successfully explained key experimental findings on I-wave physiology. Here, we critically discuss this model, point out some of its shortcomings, and suggest a number of extensions that may be necessary for it to capture additional existing and emerging data on the physiology of I-waves. PMID- 26541379 TI - Deep brain stimulation for neurodegenerative disease: a computational blueprint using dynamic causal modeling. AB - Advances in deep brain stimulation (DBS) therapeutics for neurological and psychiatric disorders represent a new clinical avenue that may potentially augment or adjunct traditional pharmacological approaches to disease treatment. Using modern molecular biology and genomics, pharmacological development proceeds through an albeit lengthy and expensive pipeline from candidate compound to preclinical and clinical trials. Such a pathway, however, is lacking in the field of neurostimulation, with developments arising from a selection of early sources and motivated by diverse fields including surgery and neuroscience. In this chapter, I propose that biophysical models of connected brain networks optimized using empirical neuroimaging data from patients and healthy controls can provide a principled computational pipeline for testing and developing neurostimulation interventions. Dynamic causal modeling (DCM) provides such a computational framework, serving as a method to test effective connectivity between and within regions of an active brain network. Importantly, the methodology links brain dynamics with behavior by directly assessing experimental task effects under different behavioral or cognitive sets. Therefore, healthy brain dynamics in circuits of interest can be defined mathematically with stimulation interventions in pathological counterparts simulated with the goal of restoring normal functionality. In this chapter, I outline the dynamic characterization of brain circuits using DCM and propose a blueprint for testing in silico, the effects of stimulation in neurodegenerative disorders affecting cognition. In particular, the models can be simulated to test whether neuroimaging correlates of nondiseased brain dynamics can be reinstantiated in a pathological setting using DBS. Thus, the key advantage of this framework is that distributed effects of DBS on neural circuitry and network connectivity can be predicted in silico. The chapter also includes a review of how DCM has been used to characterize the effects of DBS in Parkinson's disease. PMID- 26541381 TI - Computational neurostimulation for Parkinson's disease. AB - Deep brain stimulation (DBS) has had a remarkable success in treating a range of neurological and psychiatric conditions. However, efficacy remains suboptimal and patients can often develop side effects. The underlying causes of both the beneficial and detrimental effects of DBS remain incompletely understood which is delaying improvements to current DBS therapies and limiting developments of future treatments. Advancing this mechanistic understanding will require the design of appropriate models that can formalize the interaction between DBS and the cortico-basal-ganglia network. Recent advances in biophysical modeling have provided important insights into the impact of stimulation at local (neuronal membranes, electrical fields), intermediate (neural networks), and higher (phase, synchronization) levels of description. These have made important contributions to explaining neurophysiological changes during DBS (e.g., spikes, local field potentials), but such models generally do not seek to make accurate predictions about the resultant consequences on behavior. We argue that further advance will rest on models that focus on the specific computations that are performed in cortico-basal-ganglia networks, and address how DBS alters these computations and how this in turn modifies behavior. For the emergent field of computational modeling as applied to Parkinson's disease, we propose that models at mesoscopic levels of description are likely to be most valuable, with a particular focus on the role of oscillations and their relationship to behavior. It is therefore hoped that computational neurostimulation will usher in a new era of rapid, rationally derived DBS advancements for neurological and psychiatric disorders. PMID- 26541380 TI - Model-based analysis and design of waveforms for efficient neural stimulation. AB - The design space for electrical stimulation of the nervous system is extremely large, and because the response to stimulation is highly nonlinear, the selection of stimulation parameters to achieve a desired response is a challenging problem. Computational models of the response of neurons to extracellular stimulation allow analysis of the effects of stimulation parameters on neural excitation and provide an approach to select or design optimal parameters of stimulation. Here, I review the use of computational models to understand the effects of stimulation waveform on the energy efficiency of neural excitation and to design novel stimulation waveforms to increase the efficiency of neural stimulation. PMID- 26541382 TI - Computational modeling of neurostimulation in brain diseases. AB - Neurostimulation as a therapeutic tool has been developed and used for a range of different diseases such as Parkinson's disease, epilepsy, and migraine. However, it is not known why the efficacy of the stimulation varies dramatically across patients or why some patients suffer from severe side effects. This is largely due to the lack of mechanistic understanding of neurostimulation. Hence, theoretical computational approaches to address this issue are in demand. This chapter provides a review of mechanistic computational modeling of brain stimulation. In particular, we will focus on brain diseases, where mechanistic models (e.g., neural population models or detailed neuronal models) have been used to bridge the gap between cellular-level processes of affected neural circuits and the symptomatic expression of disease dynamics. We show how such models have been, and can be, used to investigate the effects of neurostimulation in the diseased brain. We argue that these models are crucial for the mechanistic understanding of the effect of stimulation, allowing for a rational design of stimulation protocols. Based on mechanistic models, we argue that the development of closed-loop stimulation is essential in order to avoid inference with healthy ongoing brain activity. Furthermore, patient-specific data, such as neuroanatomic information and connectivity profiles obtainable from neuroimaging, can be readily incorporated to address the clinical issue of variability in efficacy between subjects. We conclude that mechanistic computational models can and should play a key role in the rational design of effective, fully integrated, patient-specific therapeutic brain stimulation. PMID- 26541383 TI - Understanding the biophysical effects of transcranial magnetic stimulation on brain tissue: the bridge between brain stimulation and cognition. AB - Transcranial magnetic stimulation (TMS) is rapidly being adopted in neuroscience, medicine, psychology, and biology, for basic research purposes, diagnosis, and therapy. However, a coherent picture of how TMS affects neuronal processing, and especially how this in turn influences behavior, is still largely unavailable despite several studies that investigated aspects of the underlying neurophysiological effects of TMS. Perhaps as a result from this "black box approach," TMS studies show a large interindividual variability in applied paradigms and TMS treatment outcome can be quite variable, hampering its general efficacy and introduction into the clinic. A better insight into the biophysical, neuronal, and cognitive mechanisms underlying TMS is crucial in order to apply it effectively in the clinic and to increase our understanding of brain-behavior relationship. Therefore, computational and experimental efforts have been started recently to understand and control the effect TMS has on neuronal functioning. Especially, how the brain shapes magnetic fields induced by a TMS coil, how currents are generated locally in the cortical surface, and how they interact with complex functional neuronal circuits within and between brain areas are crucial to understand the observed behavioral changes and potential therapeutic effects resulting from TMS. Here, we review the current knowledge about the biophysical underpinnings of single-pulse TMS and argue how to move forward to fully understand and exploit the powerful technique that TMS can be. PMID- 26541384 TI - Modeling the effects of noninvasive transcranial brain stimulation at the biophysical, network, and cognitive level. AB - Noninvasive transcranial brain stimulation (NTBS) is widely used to elucidate the contribution of different brain regions to various cognitive functions. Here we present three modeling approaches that are informed by functional or structural brain mapping or behavior profiling and discuss how these approaches advance the scientific potential of NTBS as an interventional tool in cognitive neuroscience. (i) Leveraging the anatomical information provided by structural imaging, the electric field distribution in the brain can be modeled and simulated. Biophysical modeling approaches generate testable predictions regarding the impact of interindividual variations in cortical anatomy on the injected electric fields or the influence of the orientation of current flow on the physiological stimulation effects. (ii) Functional brain mapping of the spatiotemporal neural dynamics during cognitive tasks can be used to construct causal network models. These models can identify spatiotemporal changes in effective connectivity during distinct cognitive states and allow for examining how effective connectivity is shaped by NTBS. (iii) Modeling the NTBS effects based on neuroimaging can be complemented by behavior-based cognitive models that exploit variations in task performance. For instance, NTBS-induced changes in response speed and accuracy can be explicitly modeled in a cognitive framework accounting for the speed accuracy trade-off. This enables to dissociate between behavioral NTBS effects that emerge in the context of rapid automatic responses or in the context of slow deliberate responses. We argue that these complementary modeling approaches facilitate the use of NTBS as a means of dissecting the causal architecture of cognitive systems of the human brain. PMID- 26541385 TI - Computational neurostimulation in basic and translational research. PMID- 26541387 TI - Global refugees and the long road: their hope and our role! PMID- 26541386 TI - Evolutionarily Conserved Sequence Features Regulate the Formation of the FG Network at the Center of the Nuclear Pore Complex. AB - The nuclear pore complex (NPC) is the portal for bidirectional transportation of cargos between the nucleus and the cytoplasm. While most of the structural elements of the NPC, i.e. nucleoporins (Nups), are well characterized, the exact transport mechanism is still under much debate. Many of the functional Nups are rich in phenylalanine-glycine (FG) repeats and are believed to play the key role in nucleocytoplasmic transport. We present a bioinformatics study conducted on more than a thousand FG Nups across 252 species. Our results reveal the regulatory role of polar residues and specific sequences of charged residues, named 'like charge regions' (LCRs), in the formation of the FG network at the center of the NPC. Positively charged LCRs prepare the environment for negatively charged cargo complexes and regulate the size of the FG network. The low number density of charged residues in these regions prevents FG domains from forming a relaxed coil structure. Our results highlight the significant role of polar interactions in FG network formation at the center of the NPC and demonstrate that the specific localization of LCRs, FG motifs, charged, and polar residues regulate the formation of the FG network at the center of the NPC. PMID- 26541388 TI - Gender differences in factors associated with prehospital delay among acute coronary syndrome patients in Pakistan. AB - PURPOSE: To identify gender differences in prehospital delay time (PDT) and its associated factors among acute coronary syndrome (ACS) patients. DESIGN: Descriptive cross-sectional comparative study. METHODS: This study was conducted among 249 ACS patients at two tertiary care hospitals of a large metropolitan city of Pakistan. Data were collected through the modified Response to Symptoms Questionnaire. RESULTS: The median PDT of women was found to be 7 hours, compared to 3.5 hours among men (p = .001). Results of the regression analysis indicated that most women delayed because of social factors, such as attendants' responses to their symptoms (p = .002), and because they were worried about expenses required for the treatment (p = .002); yet, most men delayed owing to individual factors, such as waiting for symptoms to subside (p< .001), and not recognizing the symptoms as being cardiac related (p< .001). Having anxiety and lack of knowledge about symptoms was associated with extended PDT among both genders. CONCLUSION: Women delayed longer than men in seeking treatment for their ACS symptoms. Different factors were associated with PDT in women and men. This study may provide important insights for designing interventional studies to reduce PDT in Pakistani ACS patients. PMID- 26541389 TI - President's message: ethical practice in transcultural nursing: how are we doing? PMID- 26541391 TI - Acquisition, Analysis, and Sharing of Data in 2015 and Beyond: A Survey of the Landscape: A Conference Report From the American Heart Association Data Summit 2015. AB - BACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. CONCLUSION: There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern-day healthcare system. PMID- 26541392 TI - Time-Course Analysis of Flow Mediated Dilation for the Evaluation of Endothelial Function After a High-Fat Meal in African Americans. AB - BACKGROUND: Flow-mediated dilation (FMD) is used to assess endothelial function through changes in vascular diameter after hyperemia. High-fat meal (HFM) has been shown to induce endothelial dysfunction; recent studies, however, reported conflicting results in obese African American women (AAW). Differences in the method used to analyze FMD may explain these discrepancies. METHODS AND RESULTS: In protocol 1, we assessed the time course of FMD and compared the repeatability of FMD using the individual maximum peak dilation (FMDpeak) and the dilation at 60 seconds (FMD60). Sixteen AAW (age, 42+/-10.4 years; body mass index [BMI], 39+/-5.8 kg/m(2)) were studied on 2 occasions, 4 weeks apart, under fasting conditions (study 1 and study 2). In protocol 2, we used the most repeatable measurement from protocol 1 to assess changes in endothelial function after an HFM in 17 AAW (agen 42+/-11.1 years; BMIn 38+/-5.6 kg/m(2)). We found that FMDpeak was the most repeatable measurement (N=16; study 1, 5.31+/-3.12% and study 2, 5.80+/-2.91%; r=0.94). After an HFM, the baseline brachial artery diameter significantly increased at 2 hours (0.10 mm; 95% confidence interval [CI], 0.01-0.18; P=0.03) and at 4 hours (0.17 mm; 95% CI, 0.09-0.25; P<0.001). At 2 hours, the FMDpeak decreased compared with pre-HFM (-1.76; 95% CI, -3.55-0.02; P<=0.05). CONCLUSIONS: The individual's maximum peak dilation after hyperemia is the most consistent measure to assess the effect of an HFM on endothelial function. Endothelial dysfunction occurred at 2 hours after an HFM in AAW. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ Unique identifiers: NCT01334554 and NCT02126735. PMID- 26541393 TI - Patterns of Anticoagulation Use and Cardioembolic Risk After Catheter Ablation for Atrial Fibrillation. AB - BACKGROUND: There is significant practice variation in oral anticoagulation (OAC) use following catheter ablation for atrial fibrillation. It is not clear whether the risk of cardioembolism increases after discontinuation of OAC following catheter ablation. METHODS AND RESULTS: We identified 6886 patients within a large national administrative claims database who underwent catheter ablation for atrial fibrillation between January 1, 2005, and September 30, 2014. We assessed the effect of time off of OAC by CHA2DS2-VASc score (after adjusting for other comorbidities) on risk of cardioembolism, using Cox proportional hazards models. There was an increase in the use of non-vitamin K OAC after ablation from 0% in 2005 to 69.8% in 2014. OAC discontinuation was high, with only 60.5% and 31.3% of patients remaining on OAC at 3 and 12 months, respectively. The rate of discontinuation was higher in low-risk patients (82% versus 62.5% at 12 months for CHA2DS2-VASc 0-1 versus >=2, respectively; P<0.001). Stroke occurred in 1.4% of patients with CHA2DS2-VASc >=2 and 0.3% of those with CHA2DS2-VASc 0 or 1 over the study follow-up. The risk of cardioembolism in the first 3 months after ablation was increased among those with any time off OAC (hazard ratio 8.06 [95% CI 1.53-42.3], P<0.05). The risk of cardioembolism beyond 3 months was increased with OAC discontinuation among high-risk patients (hazard ratio 2.48 [95% CI 1.11 5.52], P<0.05) but not low-risk patients. CONCLUSION: The overall risk of stroke in postablation patients is low; however, OAC discontinuation after ablation is common and is associated with increased risk of cardioembolism for all patients within the first 3 months and for high-risk patients in the long term. Continuing OAC for at least 3 months in all patients and indefinitely in high-risk patients appears to be the safest strategy. PMID- 26541395 TI - Assessment of voice related quality of life and its correlation with socioeconomic status after total laryngectomy. AB - BACKGROUND: After total laryngectomy for laryngeal cancer, the major determinants of QOL is the patient's voice related quality of life (V-RQOL). The primary aim of this study was to assess the V-RQOL and impact of socioeconomic status over it in Indian population by using two validated scales [voice handicap index (VHI) and V-RQOL questionnaires]. METHODS: Total 104 patients underwent total laryngectomy but 71 were eligible for study. Patients filled the VHI and V-RQOL questionnaires after completion of 1 year of usage of the TEP voice. The socioeconomic status of the patients was calculated according to various domains related to their life and were divided into lower and higher status. RESULTS: A total of 76.1% patients had VHI score between 0 to 30 (minimal voice handicap), 19.7% had score between 31 to 60 (moderate voice handicap) and only 4.2% patients had VHI score more than 61 (serious voice handicap). On V-RQOL scores, 16.9% patients had score between 10 to 15 (excellent), 40.8% patients, between 16 to 20 (very good), 22.5% patients, between 21 and 25 (good voice), 15.5% patients, between 26 and 30 (fair) and only 4.2% patients scored more than 30 with poor quality of voice. Patients with lower socioeconomic group had better V-RQOL than with high socioeconomic group. CONCLUSIONS: VHI and V-RQOL scores in our series were superior to other studies due to major population with lower socioeconomic status and better social support which exists in our society. PMID- 26541394 TI - Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia. AB - Induced pluripotent stem cell bear the potential to differentiate into any desired cell type and hold large promise for disease-in-a-dish cell-modeling approaches. With the latest advances in the field of reprogramming technology, the generation of patient-specific cells has become a standard technology. However, directed and homogenous differentiation of human pluripotent stem cells into desired specific cell types remains an experimental challenge. Here, we report the development of a novel hiPSCs-based protocol enabling the generation of expandable homogenous human neural stem cells (hNSCs) that can be maintained under self-renewing conditions over high passage numbers. Our newly generated hNSCs retained differentiation potential as evidenced by the reliable generation of mature astrocytes that display typical properties as glutamate up-take and expression of aquaporin-4. The hNSC-derived astrocytes showed high activity of pyruvate carboxylase as assessed by stable isotope assisted metabolic profiling. Moreover, using a cell transplantation approach, we showed that grafted hNSCs were not only able to survive but also to differentiate into astroglial in vivo. Engraftments of pluripotent stem cells derived from somatic cells carry an inherent tumor formation potential. Our results demonstrate that hNSCs with self renewing and differentiation potential may provide a safer alternative strategy, with promising applications especially for neurodegenerative disorders. PMID- 26541396 TI - Cut points for mild, moderate, and severe pain among cancer and non-cancer patients: a literature review. AB - Defining cut points (CPs) for varying levels of pain intensity is important for assessing changes in patient's functional status, and guiding the development and evaluation of treatment options. We aimed to summarize CPs identified in the literature for mild, moderate, and severe pain on the numeric rating scale (NRS), and recommend optimal CPs for cancer and non-cancer patients. We searched MEDLINE and EMBASE (inception to May 2015) for studies that used CPs to classify pain intensity on the NRS among patients with cancer or non-cancer conditions leading to acute or chronic pain. A CP was defined as the upper bound of a mild or moderate pain category. Of 1,556 identified articles, 27 were included for review. Among patients with cancer pain, mild-moderate pain CPs ranged from 1 to 4 (mean, 3.5+/-1.08), with CP4 being the most recommended CP (80%). For moderate severe pain, CPs ranged from 4 to 7 (mean, 6.2+/-0.92), and CP6 (50%) was the optimal CPs. Among patients with non-cancer pain, mild-moderate pain CPs ranged from 2 to 5 (mean, 3.62+/-0.78), and CP4 was the most frequently used CP (52.9%). For moderate-severe non-cancer pain, CPs ranged from 4 to 8 (mean, 6.5+/-0.99), and CP6 (41.2%) was the most frequently recommended CP. A wide range of CPs for mild, moderate, and severe pain categories were identified in the literature among both cancer and non-cancer patient populations. Further studies are needed to delineate more accurate and precise CPs for pain intensity. PMID- 26541397 TI - Methods of reducing pain during bone marrow biopsy: a narrative review. AB - Bone marrow examination plays a crucial role in the diagnosis and management of various hematological and systemic diseases. Even though the procedure has been carried out for decades, it remains an extremely painful and uncomfortable experience for a majority of patients. This paper reviews the different strategies used to provide analgesia and summarizes the advantages and drawbacks of one strategy over the other. A literature review was carried out addressing the different approaches to providing pain relief during bone marrow aspiration and biopsy. Several different methods, procedure modifications and protocols are employed at various centers but pain control and analgesia remain incomplete. Local infiltration with lidocaine or similar local analgesics is the standard at most centers. Although there is limited data, there are several studies in literature demonstrating the pain relieving effects of different methods and drugs when used with local anesthetics. Sedation, usually using benzodiazepines, reduces anticipatory anxiety, provides analgesia and also short term amnesia. Combinations of different agents not only yield potent effects but also reduce the required dose of each individual drug, minimizing adverse effects. Non pharmacological factors also play key roles. Providing patients with complete and comprehensible information is vital to ensure the least amount of discomfort during the biopsy. Distraction techniques, such as cognitive behavioral therapy, hypnosis and music therapy, may also play a role in minimizing pain. PMID- 26541398 TI - Utilization of palliative care consultation service by surgical services. AB - BACKGROUND: Palliative medicine was recognized as a unique medical specialty in 2006. Since that time, the number of hospital-based palliative care services has increased dramatically. It is unclear how palliative care consultation services (PCCS) are utilized by surgical services. The purpose of this study was to examine utilization of PCCS by surgical services compared to medical services at the University of New Mexico. METHODS: A database of palliative care consultations performed at University of New Mexico Hospital between 2009 and 2013 was queried to identify consultations requested by surgical vs. medical services. Demographic, clinical, and outcome variables were compared. RESULTS: A total of 521 consultations were analyzed: 441 (85%) consultations from medical and 80 (15%) consultations from surgical services. Surgical patients were older than medical patients and more likely to be in an intensive care unit (ICU) at the time of consultation. There was no difference between referring services in indication for palliative care consultation or time from hospital admission to consultation. Surgical patients were more likely to die in the hospital compared to medical patients. Among patients discharged from the hospital alive, there was no difference between the groups in discharge disposition. More patients in both groups had a change from full code to do-not-resuscitate (DNR) status following palliative care consultation. CONCLUSIONS: Referrals for palliative care consultations are much less common from surgical than medical services. Characteristics of surgical patients suggest that palliative care consultations are reserved for older patients, critically ill patients, and those more likely to be at end-of-life. Our findings suggest the possible need for increased palliative care consultations among less critically ill patients and/or those with an improved prospect of recovery. PMID- 26541399 TI - American College of Surgeons National Surgical Quality Improvement Program as a quality-measurement tool for advanced cancer patients. AB - BACKGROUND: Multiple studies have shown the significantly increased post operative morbidity and mortality of patients undergoing palliative operations. It has been proposed by some authors that the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database can be used reliably to develop risk-calculators or as an aid for clinical decision-making in advanced cancer patients. ACS-NSQIP is a population-based database that by design only captures outcomes data for the first 30-day following an operation. We considered the suitability of these data as a tool for decision-making in the advanced cancer patient. METHODS: Six-year retrospective review of a single institution's ACS-NSQIP database for cases identified as "Disseminated Cancer". Procedures performed with palliative intent were identified and analyzed. RESULTS: Of 7,763 patients within the ACS-NSQIP database, 138 (1.8%) were identified as having "Disseminated Cancer". Of the remaining 7,625 entries only 4,486 contained complete survival data for analysis. Thirty-day mortality within the "Disseminated Cancer" group was higher when compared to all other surgical patients (7.9% vs. 0.9%, P<0.001). Explicit chart review of these 138 patients revealed that 32 (23.2%) had undergone operations with palliative intent. Overall survival for palliative and non-palliative operations was significantly different (104 vs. 709 days, P<0.001). When comparing palliative to non-palliative procedures using ACS-NSQIP data, we were unable to detect a difference in 30-day mortality (9.4% vs. 7.5%, P=0.72). CONCLUSIONS: Calculations utilizing ACS-NSQIP data fail to demonstrate the increased mortality associated with palliative operations. Patients diagnosed with advanced cancer are not adequately represented within the database due to the limited number of cases collected. Also, more suitable outcomes measures for palliative operations such as pain relief, functional status, and quality of life, are not captured. Therefore, the sole use of thirty-day morbidity and mortality data contained in the ACS-NSQIP database is insufficient to make sound decisions for surgical palliation. PMID- 26541400 TI - Debate: single-fraction treatment should be standard in the retreatment of uncomplicated bone metastases. AB - There is controversy surrounding the optimal radiotherapy dose-fractionation for retreatment of painful bone metastases. Two commonly used regimens are 8 Gy in a single-fraction or 20 Gy in five or eight fractions. Randomized evidence, including the NCIC SC.20 randomized clinical trial, has failed to standardize clinical practice. Practitioners who use single-fraction regimens cite patient convenience, fewer acute adverse effects, and better cost-effectiveness. Practitioners who prefer multiple fractions raise questions about the interpretation of data that justifies single-fraction treatment, and the possibility that single-fraction treatment may provide inferior pain relief. Given this clinical controversy, should single-fraction irradiation be standard in retreatment of uncomplicated bone metastases? In this article, two teams debate both sides of the argument with commentary to summarize the relevant issues. The conclusion from the debate is that the "standard" treatment should be individualized to the patient with shared-decision making between the oncologist, patient and family members. In a cancer patient with poor performance status and short life expectancy, single-fraction repeat radiotherapy may be preferred; in a patient with a prolonged disease course, perhaps multiple fraction retreatments would be preferred. The choice between different fractionation schemes depends on an assessment of individual patient factors, tumour factors and unique patient circumstances. PMID- 26541401 TI - Re-irradiation for painful bone metastases: evidence-based approach. AB - The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions. PMID- 26541402 TI - Radiotherapy for neuropathic pain due to bone metastases. AB - Neuropathic bone pain (NBP) due to bone metastases is estimated to affect about 15-25% of cancer patients experiencing pain. Numerous randomized trials have shown that single or multiple fraction radiotherapy (RT) for painful bone metastases produces intention-to-treat overall response rates (RRs) of approximately 60%, but there are few data on RT for NBP, per se. One randomized trial, Trans Tasman Radiation Oncology Group (TROG) 96.05 showed similar outcomes for NBP, although a single 8 Gy fraction was not proven to be as effective as fractionated treatment (20 Gy in five fractions), with RRs of 53% and 61%, respectively. A recent small, single institution series reported a comparable overall RR for NBP using a variety of fractionation schedules. Although TROG 96.05 found no statistically significant difference in the rates of re-treatment, spinal cord compression, or pathological fracture at the index site by arm, one subsequent single institution retrospective review cautioned against using single fractions for spine (the skeletal site causing the vast majority of NBP), particularly in the presence of high "spinal instability" scores. In that study, single fractions were associated with more spinal adverse events (including symptomatic vertebral compression fracture and spinal cord compression) than fractionated schedules. Although re-irradiation of bone metastases is feasible and moderately effective, there are no outcome data specific to re-treatment of NBP. In summary, NBP may appropriately be treated with fractionated RT, although single fractions may also be reasonable for patients with poor performance status and/or limited expected survival, and in centers with prolonged waiting times for fractionated treatment, given that re-treatment is possible for either. In addition, multiple fractions may be preferable for vertebral metastases in the setting of high "spinal instability" risk. PMID- 26541403 TI - Brain metastases: advances over the decades. AB - BACKGROUND: The morbidity and mortality associated with metastatic disease to brain make this problem a formidable challenge faced by health care providers and caregivers. The aim of this review is to summarize management for patients with brain metastases with a particular focus on symptom management. METHODS: A systematic review of the literature was performed. Outcomes of interest included survival, brain control (local in field and whole brain). In particular, symptom control (quality of life, neurological function and neurocognition) was examined. RESULTS: Steroids provide relief of symptoms due to intra-cerebral edema. The steroid of choice is dexamethasone. Anti-seizure medications should not be given as prophylaxis but instead be given for treatment of seizures. Depending on patient, tumour and treatment factors, management for brain metastases range from optimal supportive care including the use of steroids, whole brain radiotherapy (WBRT), radiosurgery, surgery alone or in combination. Surgery or radiosurgery improves survival for selected patients with single brain metastasis as compared to WBRT alone. Ongoing research topics include focal postoperative cavity radiation, focal fractionated regimens, molecular targeted therapies, chemoprevention of brain metastases and neurocognitive protection (such as neuro protective drugs and radiation techniques such as hippocampal sparing). CONCLUSIONS: The management of brain metastases has evolved over the decades. Other than survival and brain control (local in-field and whole brain), the outcomes of quality of life and neurocognition are becoming increasingly important. PMID- 26541404 TI - An unusual case of metastatic male breast cancer to the nasopharynx-review of literature. AB - Metastatic breast carcinoma has been described to the various areas in the head and neck region. However, these metastases are rarely found in nasopharynx. Herein we are presenting the first case of male breast carcinoma with the longest survival secondary to distant metastases in right maxillary sinus and extending to the nasopharynx with extensive skeletal & lung metastases. Here we present a case of 65-year-old male with past medical history of right breast carcinoma, presented clinically with symptoms of recurrent sinusitis. Physical examination revealed a mass in the nasopharynx, which subsequently proved to be hormonal receptor positive high-grade adenocarcinoma secondary to metastasis of primary breast cancer on biopsy. The patient received three cycles of palliative chemotherapy based on Doxorubicin with Paclitaxel weekly. In spite of that, he developed pulmonary, liver and bone metastases. Later, treatment regimen was changed to Gemcitabine, Paclitaxel and injectable Zolendronate with calcium and vitamin D supplementation. Still he didn't show any improvement and later, he developed febrile neutropenia. Then, he refused further chemotherapy and died after 12 months of receiving the best hospice care. Breast cancer is one of the most common cancers in terms of incidence and mortality; breast cancer deserves extensive studies and research in different aspects. Breast cancer metastasizing to nasopharynx would be the last diagnosis that comes to mind for a male patient presenting with clinical features suggestive of recurrent sinusitis infection. As recurrent sinusitis is a very common ailment affecting human kind and is mostly due to benign causes. Metastasis, although rare, should be included in the differential diagnosis of nasopharyngeal lesion since it may clinically mimic a benign neoplasm or primary carcinoma. Based on our clinical experience and review of literature, although it is a very rare possibility in a patient with sinusitis, still we advise not to overlook any symptoms suggestive of the etiology of recurrent sinusitis. PMID- 26541405 TI - Pain and quality of life in palliative care. PMID- 26541407 TI - Daytime and nighttime wind differentially affects hydraulic properties and thigmomorphogenic response of poplar saplings. AB - This study tested how wind in daytime and nighttime affects hydraulic properties and thigmomorphogenic response of poplar saplings. It shows that wind in daytime interrupted water balance of poplar plants by aggravating cavitation in the stem xylem under high xylem tension in the daytime, reducing water potential in midday and hence reducing gas exchange, including stomatal conductance and CO2 assimilation. The wind blowing in daytime significantly reduced plant growth, including height, diameter, leaf size, leaf area, root and whole biomass, whereas wind blowing in nighttime only caused a reduction in radial and height growth at the early stage compared with the control but decreased height:diameter ratios. In summary, the interaction between wind loading and xylem tension exerted a negative impact on water balance, gas exchanges and growth of poplar plants, and wind in nighttime caused only a small thigmomorphogenic response. PMID- 26541406 TI - HALT & REVERSE: Hsf1 activators lower cardiomyocyt damage; towards a novel approach to REVERSE atrial fibrillation. AB - BACKGROUND: Atrial fibrillation is a progressive arrhythmia, the exact mechanism underlying the progressive nature of recurrent AF episodes is still unknown. Recently, it was found that key players of the protein quality control system of the cardiomyocyte, i.e. Heat Shock Proteins, protect against atrial fibrillation progression by attenuating atrial electrical and structural remodeling (electropathology). HALT & REVERSE aims to investigate the correlation between electropathology, as defined by endo- or epicardial mapping, Heat Shock Protein levels and development or recurrence of atrial fibrillation following pulmonary vein isolation, or electrical cardioversion or cardiothoracic surgery. STUDY DESIGN: This study is a prospective observational study. Three separate study groups are defined: (1) cardiothoracic surgery, (2) pulmonary vein isolation and (3) electrical cardioversion. An intra-operative high-resolution epicardial (group 1) or endocardial (group 2) mapping procedure of the atria is performed to study atrial electropathology. Blood samples for Heat Shock Protein determination are obtained at baseline and during the follow-up period at 3 months (group 2), 6 months (groups 1 and 2) and 1 year (group 1 and 2). Tissue samples of the right and left atrial appendages in patients in group 1 are analysed for Heat Shock Protein levels and for tissue characteristics. Early post procedural atrial fibrillation is detected by continuous rhythm monitoring, whereas late post procedural atrial fibrillation is documented by either electrocardiogram or 24-h Holter registration. CONCLUSION: HALT & REVERSE aims to identify the correlation between Heat Shock Protein levels and degree of electropathology. The study outcome will contribute to novel diagnostic tools for the early recognition of clinical atrial fibrillation. TRIAL REGISTRATIONS: Rotterdam Medical Ethical Committee MEC-2014-393, Dutch Trial Registration NTR4658. PMID- 26541408 TI - Cancer patients' participation in population-based health surveys: findings from the HUNT studies. AB - BACKGROUND: The magnitude of participation bias due to non-participation should be considered for cancer patients invited to population-based surveys. We studied participation rates among persons with and without cancer in a large population based study, the Nord-Trondelag Health Study (HUNT). METHODS: Citizens 20 years or above living in the Nord-Trondelag County of Norway have been invited three times to comprehensive health surveys. The invitation files with data on sex, invitation date and participation were linked to the Cancer Registry of Norway. In a first step unadjusted crude participation rates (participants/invited persons) were estimated for cancer patients (CaPts) and non-cancer persons (NonCaPers), followed by logistic regression analyses with adjustment for age and sex. To evaluate the "practical" significance of the estimated odds ratios in the cancer diagnosis group, relative risks were also estimated comparing the observed rates to the estimated rates under the counterfactual assumption of no earlier cancer diagnosis among CaPts. RESULTS: Overall 3 % of the participants in the three HUNT studies were CaPts and 59 % of them had been diagnosed with their first life-time cancer >5 years prior to each survey. In each of the three HUNT surveys crude participation rates were similar for CaPts and NonCaPers. Adjusted for sex and age, CaPts' likelihood to participate in HUNT1 (1984-86) and HUNT2 (1995-97), but not in HUNT3 (2006-2008), was statistically significantly reduced compared to NonCaPers, equaling a relative risk of 0.98 and 0.96, respectively. The lowest odds ratio emerged for CaPts diagnosed during the last 2 years preceding a HUNT invitation. Only one-third of CaPts participating in a survey also participated in the subsequent survey compared to approximately two-thirds of NonCaPers, and 11 % of CaPts participated in all three HUNT surveys compared to 37 % of NonCaPers. CONCLUSION: In the three HUNT surveys no or only minor participation bias exist as to CaPts' participation rates. In longitudinal studies selection bias as to long-term cancer survivorship should be taken into account, the percentage of repeatedly participating CaPts diminishing more strongly than among NonCaPers. PMID- 26541409 TI - Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. AB - BACKGROUND: Recently, thousands of circular RNAs (circRNAs) have been discovered in various tissues and cell types from human, mouse, fruit fly and nematodes. However, expression of circRNAs across mammalian brain development has never been examined. RESULTS: Here we profile the expression of circRNA in five brain tissues at up to six time-points during fetal porcine development, constituting the first report of circRNA in the brain development of a large animal. An unbiased analysis reveals a highly complex regulation pattern of thousands of circular RNAs, with a distinct spatio-temporal expression profile. The amount and complexity of circRNA expression was most pronounced in cortex at day 60 of gestation. At this time-point we find 4634 unique circRNAs expressed from 2195 genes out of a total of 13,854 expressed genes. Approximately 20 % of the porcine splice sites involved in circRNA production are functionally conserved between mouse and human. Furthermore, we observe that "hot-spot" genes produce multiple circRNA isoforms, which are often differentially expressed across porcine brain development. A global comparison of porcine circRNAs reveals that introns flanking circularized exons are longer than average and more frequently contain proximal complementary SINEs, which potentially can facilitate base pairing between the flanking introns. Finally, we report the first use of RNase R treatment in combination with in situ hybridization to show dynamic subcellular localization of circRNA during development. CONCLUSIONS: These data demonstrate that circRNAs are highly abundant and dynamically expressed in a spatio-temporal manner in porcine fetal brain, suggesting important functions during mammalian brain development. PMID- 26541410 TI - What are the reasons for clinical network success? A qualitative study. AB - BACKGROUND: Clinical networks have been established to improve patient outcomes and processes of care by implementing a range of innovations and undertaking projects based on the needs of local health services. Given the significant investment in clinical networks internationally, it is important to assess their effectiveness and sustainability. This qualitative study investigated the views of stakeholders on the factors they thought were influential in terms of overall network success. METHOD: Ten participants were interviewed using face-to-face, audio-recorded semi-structured interviews about critical factors for networks' successes over the study period 2006-2008. Respondents were purposively selected from two stakeholder groups: i) chairs of networks during the study period of 2006-2008 from high- moderate- and low-impact networks (as previously determined by an independent review panel) and ii) experts in the clinical field of the network who had a connection to the network but who were not network members. Participants were blind to the performance of the network they were interviewed about. Transcribed data were coded and analysed to generate themes relating to the study aims. RESULTS: Themes relating to influential factors critical to network success were: network model principles; leadership; formal organisational structures and processes; nature of network projects; external relationships; profile and credibility of the network. CONCLUSIONS: This study provides clinical networks with guidance on essential factors for maximising optimal network outcomes and that may assist networks to move from being a 'low-impact' to 'high impact' network. Important ingredients for successful clinical networks were visionary and strategic leadership with strong links to external stakeholders; and having formal infrastructure and processes to enable the development and management of work plans aligned with health priorities. PMID- 26541411 TI - Application of standards and models in body composition analysis. AB - The aim of this review is to extend present concepts of body composition and to integrate it into physiology. In vivo body composition analysis (BCA) has a sound theoretical and methodological basis. Present methods used for BCA are reliable and valid. Individual data on body components, organs and tissues are included into different models, e.g. a 2-, 3-, 4- or multi-component model. Today the so called 4-compartment model as well as whole body MRI (or computed tomography) scans are considered as gold standards of BCA. In practice the use of the appropriate method depends on the question of interest and the accuracy needed to address it. Body composition data are descriptive and used for normative analyses (e.g. generating normal values, centiles and cut offs). Advanced models of BCA go beyond description and normative approaches. The concept of functional body composition (FBC) takes into account the relationships between individual body components, organs and tissues and related metabolic and physical functions. FBC can be further extended to the model of healthy body composition (HBC) based on horizontal (i.e. structural) and vertical (e.g. metabolism and its neuroendocrine control) relationships between individual components as well as between component and body functions using mathematical modelling with a hierarchical multi-level multi-scale approach at the software level. HBC integrates into whole body systems of cardiovascular, respiratory, hepatic and renal functions. To conclude BCA is a prerequisite for detailed phenotyping of individuals providing a sound basis for in depth biomedical research and clinical decision making. PMID- 26541412 TI - Extra-pericardial tamponade following Wolf Mini-Maze procedure: a case report. AB - BACKGROUND: Extra-pericardial tamponade is a rare life threatening condition that has not previously been reported in association with Wolf Mini-Maze procedures. In this case, atypical presentation of cardiac tamponade caused by postoperative anticoagulation resulted in a second hospitalization, a second surgery, and delayed recovery time. The goal of this case report is to increase awareness about a life threatening complication that can occur following minimally invasive cardiac surgery. CASE PRESENTATION: A 60 year old male with long standing essential hypertension, who was recently treated for atrial fibrillation utilizing the Wolf Mini-Maze procedure, experienced a postoperative international normalized ratio increase from 3.6 to 5.3 over the course of six days. Fifteen days postoperatively, the patient experienced mild exercise intolerance, his condition rapidly progressed to a constellation of symptoms including severe exercise intolerance, dyspnea, hypotension, and near syncope. A diagnosis of cardiac tamponade was made, and the patient was re-admitted to the hospital. Attempts to reverse his warfarin anticoagulation with fresh frozen plasma and vitamin K were unsuccessful after 24 h. Video-assisted thoracotomy was performed to relieve the tamponade, and during surgery he was diagnosed with extra pericardial tamponade caused by an extensive hematoma. Complications due to anticoagulation therapy required this re-admission, additional surgery, and delayed recovery. The patient has since recovered completely with no long term morbidities and is asymptomatic three years following initial presentation. CONCLUSIONS: This case marks the first time extra-pericardial tamponade has been reported post cardiothoracic intervention in English literature. Many surgical procedures require postoperative anticoagulation; in the past, warfarin has been the standard of care due to its purported reversibility. This case provides an example of the challenge presented when anticoagulating with warfarin, and the reversal of this anticoagulation. PMID- 26541413 TI - Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Therapies Ciblees dans les Sarcomes). AB - BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population. PMID- 26541414 TI - Genome-wide identification and characterization of auxin response factor (ARF) family genes related to flower and fruit development in papaya (Carica papaya L.). AB - BACKGROUND: Auxin and auxin signaling are involved in a series of developmental processes in plants. Auxin Response Factors (ARFs) is reported to modulate the expression of target genes by binding to auxin response elements (AuxREs) and influence the transcriptional activation of down-stream target genes. However, how ARF genes function in flower development and fruit ripening of papaya (Carica papaya L.) is largely unknown. In this study, a comprehensive characterization and expression profiling analysis of 11 C. papaya ARF (CpARF) genes was performed using the newly updated papaya reference genome data. RESULTS: We analyzed CpARF expression patterns at different developmental stages. CpARF1, CpARF2, CpARF4, CpARF5, and CpARF10 showed the highest expression at the initial stage of flower development, but decreased during the following developmental stages. CpARF6 expression increased during the developmental process and reached its peak level at the final stage of flower development. The expression of CpARF1 increased significantly during the fruit ripening stages. Many AuxREs were included in the promoters of two ethylene signaling genes (CpETR1 and CpETR2) and three ethylene synthesis-related genes (CpACS1, CpACS2, and CpACO1), suggesting that CpARFs might be involved in fruit ripening via the regulation of ethylene signaling. CONCLUSIONS: Our study provided comprehensive information on ARF family in papaya, including gene structures, chromosome locations, phylogenetic relationships, and expression patterns. The involvement of CpARF gene expression changes in flower and fruit development allowed us to understand the role of ARF mediated auxin signaling in the maturation of reproductive organs in papaya. PMID- 26541415 TI - A hot-electron thermophotonic solar cell demonstrated by thermal up-conversion of sub-bandgap photons. AB - The direct conversion of solar energy to electricity can be broadly separated into two main categories: photovoltaics and thermal photovoltaics, where the former utilizes gradients in electrical potential and the latter thermal gradients. Conventional thermal photovoltaics has a high theoretical efficiency limit (84%) but in practice cannot be easily miniaturized and is limited by the engineering challenges of sustaining large (>1,000 K) temperature gradients. Here we show a hot-carrier-based thermophotonic solar cell, which combines the compact nature of photovoltaic devices with the potential to reach the high-efficiency regime of thermal photovoltaics. In the device, a thermal gradient of 500 K is established by hot electrons, under Stokes illumination, rather than by raising the temperature of the material itself. Under anti-Stokes (sub-bandgap) illumination we observe a thermal gradient of ~20 K, which is maintained by steady-state Auger heating of carriers and corresponds to a internal thermal up conversion efficiency of 30% between the collector and solar cell. PMID- 26541417 TI - Exploring the reactivity of manganese(III) complexes with diphenolate-diamino ligands in rac-lactide polymerization. AB - Manganese(III) complexes of tetradentate diphenolate-diamino (NNOO(2-)) ligands were prepared from aerobic reaction of MnCl2 with the respective ligands in basic methanolic solution. Methoxide complexes (NNOO)Mn(OMe)(MeOH)0-1 were obtained for three ligands, while others only provided the respective chloride complexes (NNOO)Mn(Cl)(MeOH). Complexes were analyzed by X-ray diffraction studies and octahedral complexes showed evidence of Jahn-Teller distortions. Magnetic moments determined in MeOD were indicative of high-spin Mn(III)-d(4) complexes (MUeff = 4.2-4.6MUB). Methoxide complexes were active in the coordination-insertion polymerization of rac-lactide (130 degrees C, 0.33-1.0 mol% catalyst loading) to yield atactic polylactic acid with moderate molecular weight control. Polymerization activity was reduced, but not suppressed by the presence of protic impurities. Chloride complexes showed less activity and only in the presence of external alcohol, indicative of an activated-monomer mechanism. PMID- 26541416 TI - Inequalities in mortality by socioeconomic factors and Roma ethnicity in the two biggest cities in Slovakia: a multilevel analysis. AB - BACKGROUND: The socioeconomic and ethnic composition of urban neighbourhoods may affect mortality, but evidence on Central European cities is lacking. The aim of this study was to assess the associations between socioeconomic and ethnic neighbourhood indicators and the mortality of individuals aged 20-64 years old in the two biggest cities of the Slovak Republic. METHODS: We obtained data on the characteristics of neighbourhoods and districts (educational level, unemployment, income and share of Roma) and on individual mortality of residents aged 20-64 years old, for the two largest cities in the Slovak Republic (Bratislava and Kosice) in the period 2003-2005. We performed multilevel Poisson regression analyses adjusted for age and gender on the individual (mortality), neighbourhood (education level and share of Roma in population) and district levels (unemployment and income). RESULTS: The proportions of Roma and of low-educated residents were associated with mortality at the neighbourhood level in both cities. Mutually adjusted, only the association with the proportion of Roma remained in the model (risk ratio 1.02; 95 % confidence interval 1.01-1.04). The area indicators - high education, income and unemployment - were not associated with mortality. CONCLUSION: The proportion of Roma is associated with early mortality in the two biggest cities in the Slovak Republic. PMID- 26541418 TI - Nursing performance under high workload: a diary study on the moderating role of selection, optimization and compensation strategies. AB - AIMS: The aim of this study was to investigate whether selective optimization with compensation constitutes an individualized action strategy for nurses wanting to maintain job performance under high workload. BACKGROUND: High workload is a major threat to healthcare quality and performance. Selective optimization with compensation is considered to enhance the efficient use of intra-individual resources and, therefore, is expected to act as a buffer against the negative effects of high workload. DESIGN: The study applied a diary design. Over five consecutive workday shifts, self-report data on workload was collected at three randomized occasions during each shift. Self-reported job performance was assessed in the evening. Self-reported selective optimization with compensation was assessed prior to the diary reporting. METHODS: Data were collected in 2010. Overall, 136 nurses from 10 German hospitals participated. Selective optimization with compensation was assessed with a nine-item scale that was specifically developed for nursing. The NASA-TLX scale indicating the pace of task accomplishment was used to measure workload. Job performance was assessed with one item each concerning performance quality and forgetting of intentions. RESULTS: There was a weaker negative association between workload and both indicators of job performance in nurses with a high level of selective optimization with compensation, compared with nurses with a low level. Considering the separate strategies, selection and compensation turned out to be effective. CONCLUSION: The use of selective optimization with compensation is conducive to nurses' job performance under high workload levels. This finding is in line with calls to empower nurses' individual decision-making. PMID- 26541419 TI - Conjugated bile acids in gallbladder bile and serum as potential biomarkers for cholesterol polyps and adenomatous polyps. AB - PURPOSE: To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). METHODS: Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. RESULTS: These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 ug/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (<=12 ug/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. CONCLUSIONS: The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs. PMID- 26541420 TI - Androgen receptor CAG repeat length and estrogen receptor status in postmenopausal breast cancer prognosis. AB - PURPOSE: The influence of the androgen receptor (AR) CAG repeat polymorphism on breast cancer is controversial. We investigated the combined effects of CAG repeat length and estrogen receptor (ER) status on prognosis in 355 postmenopausal women with primary breast cancer. METHODS: CAG repeat length was determined by the HUMARA test. Relapse-free survival (RFS) and overall survival (OS) according to the X-weighted CAG repeat biallelic mean (XWBM) were investigated by univariate and multivariate analysis. RESULTS: XWBM was not associated with RFS or OS, but a significant interaction between XWBM and ER status (p = 0.002) was found for OS. ER-negative patients with median XWBM <20 showed lower OS than ER-negative/XWBM >=20 patients (HR = 0.270; 95% Cl: 0.073 0.999). ER-negative/XWBM <20 patients also had significantly lower OS than ER positive women, irrespective of CAG repeat length (p<0.001). Accordingly, estimated OS was lowest in ER-negative patients with XWBM <20 (OS: 0.63, 95% CI: 0.41-0.79) and highest in ER-positive patients with XWBM <20 (OS: 0.95, 95% CI: 0.90-0.97). CONCLUSIONS: Our data suggest that short CAG repeat length is associated with increased risk of death in ER-negative disease but is related to better survival when ER is expressed. These findings are in agreement with the hypothesis that AR may stimulate or inhibit breast cancer growth depending on ER status, AR transactivation, and the endocrine-metabolic environment of breast tumors. Evaluation of CAG repeat length together with ER status could help improve the estimation of the risk of death, with possible implications for the optimization of standard breast cancer treatment and implementation of prevention strategies. PMID- 26541421 TI - Binaural beats increase interhemispheric alpha-band coherence between auditory cortices. AB - Binaural beats (BBs) are an auditory illusion occurring when two tones of slightly different frequency are presented separately to each ear. BBs have been suggested to alter physiological and cognitive processes through synchronization of the brain hemispheres. To test this, we recorded electroencephalograms (EEG) at rest and while participants listened to BBs or a monaural control condition during which both tones were presented to both ears. We calculated for each condition the interhemispheric coherence, which expressed the synchrony between neural oscillations of both hemispheres. Compared to monaural beats and resting state, BBs enhanced interhemispheric coherence between the auditory cortices. Beat frequencies in the alpha (10 Hz) and theta (4 Hz) frequency range both increased interhemispheric coherence selectively at alpha frequencies. In a second experiment, we evaluated whether this coherence increase has a behavioral aftereffect on binaural listening. No effects were observed in a dichotic digit task performed immediately after BBs presentation. Our results suggest that BBs enhance alpha-band oscillation synchrony between the auditory cortices during auditory stimulation. This effect seems to reflect binaural integration rather than entrainment. PMID- 26541422 TI - Trap-Assisted Transport and Non-Uniform Charge Distribution in Sulfur-Rich PbS Colloidal Quantum Dot-based Solar Cells with Selective Contacts. AB - This study reports evidence of dispersive transport in planar PbS colloidal quantum dot heterojunction-based devices as well as the effect of incorporating a MoO3 hole selective layer on the charge extraction behavior. Steady state and transient characterization techniques are employed to determine the complex recombination processes involved in such devices. The addition of a selective contact drastically improves the device efficiency up to 3.15% (especially due to increased photocurrent and decreased series resistance) and extends the overall charge lifetime by suppressing the main first-order recombination pathway observed in device without MoO3. The lifetime and mobility calculated for our sulfur-rich PbS-based devices are similar to previously reported values in lead rich quantum dots-based solar cells. Nevertheless, strong Shockley-Read-Hall mechanisms appear to keep restricting charge transport, as the equilibrium voltage takes more than 1 ms to be established. PMID- 26541423 TI - Three dimensional printing of an atrial septal defect: Is it multimodality imaging? PMID- 26541424 TI - Endotracheal Intubation in Neonates: A Prospective Study of Adverse Safety Events in 162 Infants. AB - OBJECTIVE: To determine the rate of adverse events associated with endotracheal intubation in newborns and modifiable factors contributing to these events. STUDY DESIGN: We conducted a prospective, observational study in a 100-bed, academic, level IV neonatal intensive care unit from September 2013 through June 2014. We collected data on intubations using standardized data collection instruments with validation by medical record review. Intubations in the delivery or operating rooms were excluded. The primary outcome was an intubation with any adverse event. Adverse events were defined and tracked prospectively as nonsevere or severe. We measured clinical variables including number of attempts to successful intubation and intubation urgency (elective, urgent, or emergent). We used logistic regression models to estimate the association of these variables with adverse events. RESULTS: During the study period, 304 intubations occurred in 178 infants. Data were available for 273 intubations (90%) in 162 patients. Adverse events occurred in 107 (39%) intubations with nonsevere and severe events in 96 (35%) and 24 (8.8%) intubations, respectively. Increasing number of intubation attempts (OR 2.1, 95% CI, 1.6-2.6) and emergent intubations (OR 4.7, 95% CI, 1.7 13) were predictors of adverse events. The primary cause of emergent intubations was unplanned extubation (62%). CONCLUSIONS: Adverse events are common in the neonatal intensive care unit, occurring in 4 of 10 intubations. The odds of an adverse event doubled with increasing number of attempts and quadrupled in the emergent setting. Quality improvement efforts to address these factors are needed to improve patient safety. PMID- 26541425 TI - Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents. AB - OBJECTIVE: To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN: We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS: Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS: Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities. PMID- 26541426 TI - Short Sleep Duration in the First Years of Life and Obesity/Overweight at Age 4 Years: A Birth Cohort Study. AB - OBJECTIVE: To investigate whether short sleep duration from the first year of life influenced weight at an early age. STUDY DESIGN: During 2004, children born in Pelotas, Brazil, were enrolled in a cohort study. Sleeping habits during the previous 2 weeks were assessed, and the children were weighed and measured at 1-, 2-, and 4-year follow-ups. Overweight and obesity at 4 years were defined according to World Health Organization z-scores for body mass index for age. Short sleep duration was defined as fewer than 10 hours of sleep per night at any follow-up. RESULTS: Out of the 4263 live births, 4231 were recruited. The prevalence of short sleep duration at any follow-up from 1-4 years of age was 10.1%. At 4 years of age, 201 children were obese (5.3%), and 302 (8%) were overweight. Among short sleepers, the prevalence ratio for overweight/obesity after adjusting for maternal and children's characteristics was 1.32 (1.03; 1.70). CONCLUSIONS: Children who slept for fewer than 10 hours per night at any follow-up from 1-4 years of age were more likely to be overweight or obese at 4 years of age, despite their sociodemographic and sleep characteristics. PMID- 26541427 TI - A Pilot Study Investigating Neuropsychological Consultation as an Intervention for Persistent Postconcussive Symptoms in a Pediatric Sample. AB - OBJECTIVE: To examine the efficacy of a one-time neuropsychological consultation as an intervention for youth with persistent postconcussive symptoms following mild traumatic brain injury. STUDY DESIGN: Using a prospective interrupted time series design, we enrolled 80 patients aged 8-17 years referred consecutively for clinical neuropsychological consultation. Patients needed to have sustained injury between 2 and 12 months prior to enrollment. Parent and child postconcussive symptom ratings were used as the primary outcome measures and were collected at 6 time points, 3 before the neuropsychological consultation and 3 after. Repeated measure ANOVA was used to estimate the magnitude of change in symptom ratings before and after the neuropsychological intervention. RESULTS: The decrease in symptoms for the week prior to consultation was nonsignificant by both child (P = .63) and parent (P = .19) report. In contrast, for both reporters, the decrease in symptoms at 1 week and 3 months postconsultation was significant (P < .0001). The difference in reported change was also significant when comparing the week before the intervention to the 3 months after (child: P < .0001; parent: P = .0009). CONCLUSIONS: Postconcussive symptoms decreased significantly following the neuropsychological consultation. The primary limitation of the study is that it lacked randomization and a control group. The results warrant further research into the benefits of neuropsychological consultation after mild traumatic brain injury and provide justification for clinical providers to consider referring to neuropsychologists in the face of persistent postconcussive symptoms. PMID- 26541428 TI - Fine-scale monitoring of shifts in microbial community composition after high organic loading in a pilot-scale membrane bioreactor. AB - In biological wastewater treatment, municipal wastewater sometimes undergoes unexpected changes in physicochemical parameters, such as organic carbon concentration. The aim of this study was to understand how microbial communities in activated sludge in a membrane bioreactor (MBR) adapt to high organic loading and maintain their degradation ability during reactor operation. A pilot-scale MBR was operated for 19 days. On day 8, the concentration of organic matter in the synthetic wastewater increased from 450 to 900 mg chemical oxygen demand (COD)/L. Even under conditions of high organic loading, COD removal rates were high, ranging from 85.3 to 91.4%. High-throughput sequencing of 16S rRNA genes revealed that microbial communities changed drastically with increased organic loading. After day 8, Aquabacterium- and Azospira-related operational taxonomic units (OTUs) belonging to the class beta-proteobacteria became dominant; this potentially enhanced the degradation of organic substances and decreased activated sludge microbial diversity. Due to the use of dissolved oxygen (DO) for degradation of organic substances, DO levels in the reactor decreased. This led to an increase in a subset of OTUs related to not only aerobic but also anaerobic bacteria, e.g., those in the class Clostridia. During this period, anaerobic microorganisms may have contributed to the degradation of organic substances to maintain MBR performance. On the other hand, high-throughput sequencing also made it possible to identify yet-to-be cultured or minor microorganisms affiliated with the candidate phylogenetic division SR1 and ammonia-oxidizing archaea in activated sludge. PMID- 26541429 TI - Non-prion-type transmission in A53T alpha-synuclein transgenic mice: a normal component of spinal homogenates from naive non-transgenic mice induces robust alpha-synuclein pathology. PMID- 26541430 TI - Biomolecule-assisted synthesis of In(OH)3 nanocubes and In2O3 nanoparticles: photocatalytic degradation of organic contaminants and CO oxidation. AB - The synthesis of nanostructured materials without any hazardous organic chemicals and expensive capping reagents is one of the challenges in nanotechnology. Here we report on the L-arginine (a biomolecule)-assisted synthesis of single crystalline cubic In(OH)3 nanocubes of a size in the range of 30-60 nm along the diagonal using hydrothermal methods. Upon calcining at 750 degrees C for 1 h in air, In(OH)3 nanocubes are transformed into In2O3 nanoparticles (NPs) with voids. The morphology transformation and formation of voids with the increase of the calcination temperature is studied in detail. The possible mechanism of the voids' formation is discussed on the basis of the Kirkendall effect. The photocatalytic properties of In(OH)3 nanocubes and In2O3 NPs are studied for the degradation of rhodamin B and alizarin red S. Furthermore, the CO oxidation activity of In(OH)3 nanocubes and In2O3 NPs is examined. The photocatalytic and CO oxidation activity are measured to be higher for In2O3 NPs than for In(OH)3 nanocubes. This is attributed to the lower energy gap and higher specific surface area of the former. The present green synthesis has potential for the synthesis of other inorganic nanomaterials. PMID- 26541431 TI - En face enhanced depth imaging optical coherence tomography of polypoidal choroidal vasculopathy. AB - PURPOSE: To analyse retinal and choroidal changes associated with polypoidal choroidal vasculopathy (PCV) using en face spectral-domain optical coherence tomography (SD-OCT). METHODS: In this retrospective and descriptive study, we collected imaging of patients affected with PCV examined using enhanced depth imaging (EDI) SD-OCT, fluorescein and indocyanine green angiography for a qualitative analysis. The three-dimensional reconstruction of 197 transverse sections with EDI SD-OCT at 30 MUm intervals provided a virtual macular brick through which 496 sections in the coronal plane resulted in a C-scan or en face OCT image. RESULTS: 30 eyes of 30 patients affected with PCV were studied. En face OCT revealed polyps as roundish structures visible deeper than pigment epithelium layer, attached to its posterior face, easily detected in all cases. Hyper-reflective dots were visible on en face OCT in all cases within the retinal layers, associated to a well-defined dark area suggesting serous exudation in 27 eyes. The abnormal choroidal network was identified in four eyes. At the Bruch membrane level, all polyps were associated with a localised back shadowing, and were no more visible at the choriocapillaris layer level. Large choroidal vessels were visible in all eyes, mainly at the polypoidal lesion periphery, not directly behind. CONCLUSIONS: En face OCT imaging using SD-OCT is an easy, reproducible, non-invasive and effective tool to visualise and to understand retinal and choroidal changes PCV. It provides complementary morphological information, describes new semiological entities and might substitute other exams in the future, without dye injection. PMID- 26541432 TI - Influence of involuntary eyelid spasms on corneal topographic and eyelid morphometric changes in patients with hemifacial spasm. AB - BACKGROUND/AIMS: In patients with hemifacial spasm (HFS), treatment relieves eyelid spasms on the affected side, thus changes in corneal topography and eyelid morphometry may be observed after treatment. We aimed to evaluate these parameters during a 4-month period in patients with HFS treated with botulinum toxin A (BTX-A). METHODS: This prospective study evaluated eyelid morphometric and corneal topographic changes in patients with HFS before onabotulinum toxin A application, and after 15 days and 2, 3 and 4 months. RESULTS: 24 patients were treated with BTX-A. On the normal side, the mean palpebral fissure height (PF), interpalpebral surface area (ISA), steep K and astigmatism values were 8.7+/-1.98 mm, 122.09+/-39.37 mm2, 44.99+/-1.45 D and 0.9+/-0.64 D, respectively, before treatment. A statistically significant difference was not observed in these parameters after treatment (p>0.05). On the affected side, the mean PF, ISA, steep K and astigmatism were 5.5+/-1.77 mm, 67.68+/-28.49 mm2, 46.91+/-3.57 D and 2.63+/-2.46 D, respectively, before treatment. We observed a statistically significant (p<0.05) increase in the mean PF and ISA on the affected side 15 days (8.36+/-1.91 mm and 115.92+/-34.44 mm2, respectively), 2 months (8.18+/-1.80 mm and 112.22+/-33.57 mm2, respectively) and 3 months (7.27+/-1.65 mm and 95.48+/ 27.80 mm2, respectively) after treatment. A statistically significant decrease in steep K and astigmatism was observed at 2 months (45.14+/-1.20 D and 1.01+/-0.58 D, respectively) and 3 months (45.64+/-1.77 D and 1.36+/-1.31 D, respectively) after treatment. CONCLUSIONS: The results suggest that treatment with BTX-A in patients with HFS leads to eyelid and corneal changes on the affected eye that are significant during the known period of action of the toxin. Thus, caution should be taken when performing ophthalmological examination in patients with HFS, since it may vary according to BTX-A period of action. PMID- 26541433 TI - Influence of epiretinal membrane on the measurement of peripapillary retinal nerve fibre layer thickness using spectral-domain coherence tomography. AB - BACKGROUND/AIMS: To investigate the effect of epiretinal membrane (ERM) on peripapillary retinal nerve fibre layer (RNFL) thickness measurements using spectral-domain optical coherence tomography (Spectralis; Heidelberg Engineering). METHODS: A total of 134 patients with idiopathic ERM and 63 healthy controls were included in this observational comparative study. We categorised ERMs into three severity grades, based on retinal appearance in macular scans. All eyes with ERM were classified into two groups; those involving the peripapillary scan area (ERM+pp, n=68 eyes) and not involving the peripapillary scan area (ERM-pp, n=66 eyes) using the macular disc scan. Peripapillary RNFL thickness was compared between related subgroups as (ERM+pp) or (ERM-pp) group. RESULTS: Temporal peripapillary RNFL thickness was significantly greater in the ERM+pp group (109.44+/-22.91 MUm), followed by the ERM-pp (82.60+/-11.77 MUm, p<0.001) and control (75.42+/-10.49 MUm, p<0.001) groups. Temporal peripapillary RNFL thickness significantly increased with ERM grade in the ERM+pp and ERM-pp groups (both p<0.001). The peripapillary RNFL thickness was overestimated (exceeded 99th percentile) in the temporal sector in 49 eyes (72.1%) in the ERM+pp group and in 5 eyes (7.6%) in the ERM-pp group. CONCLUSIONS: Temporal and global peripapillary RNFL thickness is significantly higher in eyes with ERM, especially when the ERM extends into the peripapillary area. However, some eyes with an ERM that does not involve the peripapillary scan area still show peripapillary RNFL thickening. Measured peripapillary RNFL thickness was significantly and positively correlated with ERM severity. PMID- 26541434 TI - MicroRNAs in retina during development of experimental autoimmune uveoretinitis in rats. AB - PURPOSE: To determine the changes in the expression profiles of microRNAs (miRNAs) in retinas during the development of experimental autoimmune uveoretinitis (EAU) in rats. METHODS: The levels of interleukin-1beta (IL-1beta) and monocyte chemoattractant protein-1 (MCP-1) were measured in aqueous humour samples and supernatants of homogenised posterior eye cups obtained from Lewis rats immunised with interphotoreceptor retinoid binding protein peptide (R14) and complete Freund's adjuvant. Microarray analysis was performed to determine the miRNA profiles in the retina of eyes with EAU on days 0 (baseline), 7, 14 and 21 after immunisation. RESULTS: The levels of IL-1beta and MCP-1 in the aqueous humour and the supernatants of posterior eye cups were significantly elevated in eyes with EAU, and the levels corresponded with the stage of the EAU. On day 14 after immunisation, the expressions of nine miRNAs (miRNA-223, 142-5p, 142-3p, 21, 146a, 146b, 1949, 1188-3p and 193) were significantly elevated, and the expressions of four miRNAs (miRNA-181a, 183*, 124* and 331) were downregulated relative to the baseline. Quantitative PCR analyses confirmed the elevation of miRNA-223 and miRNA-146 and the downregulation of miRNA-181a in retinas with EAU on day 14 after immunisation. In situ hybridisation confirmed increased expression of miR-223 and miR-146 in retinas with EAU. CONCLUSIONS: Several miRNAs were significantly increased or decreased in retinas during the course of EAU. The expression of miR-223 and miR-146a corresponded with the clinical score of the EAU and elevation of IL-1beta/MCP-1 in the eye with EAU. Further studies are required to clarify the role of miRNA in eyes with autoimmune uveoretinitis. PMID- 26541435 TI - Predicting vision gains with anti-VEGF therapy in neovascular age-related macular degeneration patients by using low-luminance vision. AB - BACKGROUND/AIMS: To evaluate baseline low-luminance visual acuity (LLVA) as a predictor of visual acuity improvement in patients with neovascular (wet) age related macular degeneration (wAMD) receiving antivascular endothelial growth factor A (anti-VEGF) therapy. METHODS: In the HARBOR trial, 1084 treatment-naive patients >=50 years of age with subfoveal wAMD received intravitreal ranibizumab 0.5 or 2.0 mg monthly or as needed. To measure LLVA, patients read a normally illuminated ETDRS (Early Treatment Diabetic Retinopathy Study) chart with a neutral density filter placed in front of the study eye. Patients were assigned into quartiles based on the magnitude of the difference between best-corrected visual acuity under optimal luminance (BCVA) and LLVA (BCVA-LLVA gap). The association between mean change in BCVA from baseline and BCVA-LLVA gap at baseline was analysed using a general linear model. RESULTS: A smaller baseline BCVA-LLVA gap predicted significantly higher BCVA gains over 24 months (p<0.0001 at each month; Pearson correlation), even after controlling for baseline BCVA or stratifying by treatment arm. Patients in the smallest baseline BCVA-LLVA gap quartile gained an average of +13.4 letters compared with +2.4 letters for patients in the widest baseline BCVA-LLVA gap quartile. At months 12 and 24, the smallest baseline BCVA-LLVA gap quartile had the highest proportion of >=15->=30 letter gain, and the widest baseline BCVA-LLVA gap quartile had the highest proportion of >=15-/>=30-letter loss (p<0.0001; Fisher's exact test). CONCLUSIONS: The baseline BCVA-LLVA gap is a significant predictor of visual acuity response to anti-VEGF treatment in patients with wAMD. TRIAL REGISTRATION NUMBER: NCT00891735; Post-results. PMID- 26541436 TI - Cycloplegic autorefraction versus subjective refraction: the Tehran Eye Study. AB - AIM: To compare cycloplegic autorefraction with non-cycloplegic subjective refraction across all age and refractive error groups. METHODS: In a cross sectional study with random stratified cluster sampling, 160 clusters were chosen from various districts proportionate to the population of each district in Tehran. Following retinoscopy and autorefraction with the 0.25 D bracketing (Topcon KR-8000, Topcon, Tokyo, Japan), all participants had a subjective refraction. Then all participants underwent cycloplegic autorefraction. RESULTS: The final analysis was performed on 3482 participants with a mean age of 31.7 years (range 5-92 years). Based on cycloplegic and subjective refraction, mean spherical equivalent (SE) was +0.31+/-1.80 and -0.32+/-1.61 D, respectively (p<0.001). The 95% limits of agreement (LoA) between these two types of refraction were from -0.40 to 1.70 D. The largest difference between these two types of refraction was seen in the age group of 5-10 years (1.11+/-0.60 D), and the smallest difference was in the age group of >70 years (0.34+/-0.45 D). The 95% LoA was -0.52 to 0.89 D in patients with myopia and -0.12 to 2.04 D in patients with hyperopia. We found that female gender (coefficients=0.048), older age (coefficients=-0.247), higher education (coefficients=-0.043) and cycloplegic SE (coefficients=-0.472) significantly correlated with lower intermethod differences. CONCLUSIONS: The cycloplegic refraction is more sensitive than the subjective one to measure refractive error at all age groups especially in children and young adults. The cyclorefraction technique is highly recommended to exactly measure the refractive error in momentous conditions such as refractive surgery, epidemiological researches and amblyopia therapy, especially in hypermetropic eyes and paediatric cases. PMID- 26541437 TI - Development of certified environmental management in hospital and outpatient haemodialysis units. AB - INTRODUCTION: The environmental impact of haemodialysis is very high. Institutional activity in this sense is important, even in the production of references. Voluntary environmental management systems (EMS), environmental management and auditing systems (EMAS) and the International Organization for Standardization standards (ISO 14001) are important tools for environmental protection, together with legislation, taxation and tax benefits. OBJECTIVES: To determine the degree of implementation of EMS in hospital units and outpatient haemodialysis in the Spanish National Health System to provide a group of reference centres in environmental management in this healthcare activity. METHODS: Development of a list by autonomous communities showing hospital and outpatient dialysis units using an EMAS and/or ISO 14001 in 2012-2013. The sources of information were the Spanish National Catalogue of Hospitals, Spanish Registry of Healthcare Certification and Accreditation, European and regional EMAS records, world ISO registrations, dialysis centre lists from scientific societies and patients, responses from accredited entities in Spain for environmental certification and the institutional website of each haemodialysis centre identified. RESULTS: Of the 210 hospitals with a dialysis unit, 53 (25%) have the ISO 14001 and 15 of these also have an EMAS). This constitutes 30% of all hospital dialysis chairs in Spain: 1,291 (of 4,298). Only 11 outpatient clinics are recorded, all with the ISO 14001. DISCUSSION: There is no official documentation of the implementation of EMS in dialysis units. Making this list provides an approach to the situation, with special reference to haemodialysis because of its significant environmental impact. PMID- 26541438 TI - Eculizumab for the treatment of an atypical hemolytic uremic syndrome with mutations in complement factor I and C3. PMID- 26541439 TI - TGR5 and Immunometabolism: Insights from Physiology and Pharmacology. AB - In the past decade substantial progress has been made in understanding how the insurgence of chronic low-grade inflammation influences the physiology of several metabolic diseases. Tissue-resident immune cells have been identified as central players in these processes, linking inflammation to metabolism. The bile acid responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and its activation mediates potent anti-inflammatory effects. Herein, we summarize recent advances in TGR5 research, focusing on the downstream effector pathways that are modulated by TGR5 activators, and on its therapeutic potential in inflammatory and metabolic diseases. PMID- 26541440 TI - Low-dose CT angiography of the abdominal aorta and reduced contrast medium volume: Assessment of image quality and radiation dose. AB - AIM: To determine the effect of using 80 kV tube voltage and a reduced amount of contrast medium on the image quality and radiation dose of computed tomography angiography (CTA) of the abdominal aorta. MATERIALS AND METHODS: Patients who were referred for a CTA examination of the abdominal aorta were included in this technical efficacy study. Thirty patients were divided randomly into two groups. Fifteen patients underwent a dual-energy CT (DECT) protocol (Group A). Fifteen patients were scanned with the use of an automated tube potential selection algorithm tool (Group B). In both protocols, a test bolus injection of 10 ml ioversol (350 mg iodine/ml) was used, followed by 20 ml of 1:1 saline-diluted contrast medium. Quantitative analysis comprised determination of the mean attenuation and contrast-to-noise ratio. Qualitative image analysis was performed independently by five radiologists. The estimated radiation dose in terms of CT dose index and effective dose was recorded and compared with a standard 120 kV protocol. RESULTS: In Group B, six patients underwent CTA at 80 kV, seven patients underwent CTA at 100 kV and two patients underwent CTA at 120 kV. The mean contrast-enhancement values of Group A (80 kV) and the 80 kV subgroup of Group B were 16.5% and 27.6% higher compared to the 100 kV subgroup of Group B, these differences were, however, not significant. There were no significant differences in mean image quality between groups. In patients undergoing CTA at 80 kV the effective dose decreased by up to 51.3% compared to a conventional 120 kV CTA protocol. CONCLUSIONS: The findings of this study support the hypothesis that 80 kV in CTA of the abdominal aorta can reliably be used with only 30 ml contrast medium in total and a 50% reduction in radiation dose. The overall image quality was diagnostically adequate; however, it appeared to be suboptimal in patients with a BMI above 28 kg/m(2). PMID- 26541441 TI - Glenohumeral Dysplasia Following Neonatal Brachial Plexus Palsy: Presentation and Predictive Features During Infancy. AB - PURPOSE: To evaluate the presence and degree of glenohumeral dysplasia (GHD) in infants undergoing surgical exploration for neonatal brachial plexus palsy (NBPP) and to identify potential predictive factors of early maladaptive shoulder morphology. METHODS: We included all consecutive patients with NBPP who underwent surgical exploration of their brachial plexus and who had a preoperative magnetic resonance imaging scan at our institution over a 3-year period. Demographic, therapy, and surgical data were collected. Imaging was reviewed for glenoid morphology, glenoid version, percent humeral head anterior to the scapula, and alpha angle. RESULTS: Of 116 infants who presented to our institution during this 3-year period, 19 (16%) underwent surgical exploration and were included in the study. Median age at the time of the scan was 16 weeks (interquartile range, 14 46 weeks). Fourteen of 19 (74%) had GHD of Waters class 2 or increased malformation. Babies who had more severe palsies underwent earlier surgery and had less severe GHD at the time of surgery than did those with less severe palsies who had surgery later. Less severe GHD was associated with more severe palsies, as indicated by Narakas classification and number of root avulsions. Active external rotation was almost universally absent whereas other shoulder movements were present to varying degrees. More severe GHD was associated with greater total shoulder active range of motion and greater pectoralis major muscle mass. CONCLUSIONS: Glenohumeral dysplasia occurs often and early in NBPP and may occur in the absence of restricted range of motion. Predictors include increasing age and factors related to muscular imbalance. As such, GHD likely affects the functional outcome that may be achieved with reinnervation, and early screening may improve outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV. PMID- 26541442 TI - Floral resource limitation severely reduces butterfly survival, condition and flight activity in simplified agricultural landscapes. AB - Agricultural intensification has a strong negative impact on farmland biodiversity (including flower-visiting insects), but understanding the mechanisms involved in this requires experimental work. We document the impact of nectar limitation on the performance of a flower-visiting insect, the meadow brown butterfly Maniola jurtina. We conducted two types of experiments: a field experiment in agricultural landscapes with grasslands of different management intensity and an experiment in outdoor flight cages in which the nectar supply was simulated. For the field experiment, we introduced an array of nectar resources in intensively managed, nectar-poor meadows and in extensively managed, flower-rich grasslands and counted flower visitors. Despite higher butterfly abundance in the extensive meadows, our introduced nectar sources were more frequently visited in intensive meadows, indicating the lack of floral resources. The 48-h confinement under nectar-poor conditions in the flight cages had a strong negative effect on body condition, flight activity and lifetime survival compared to butterflies under nectar-rich conditions. Female lifespan was reduced by 22% and male lifespan even by 43%. Agricultural landscapes that provide limited amounts of floral nectar, and no high-quality, preferred nectar sources relative to the needs of the flower-visiting species, may create ecological sinks. Regards an insect's performance, the simple presence of nectar is not necessarily functionally adequate. The effectiveness of agri-environmental schemes for flower-visiting insects (e.g. flower strips) could be improved based on ecological and evolutionary insights on the effects of specific nectar quantities and qualities. PMID- 26541444 TI - [Calcium and parathormone control after total thyroidectomy]. PMID- 26541443 TI - Understanding the influence of personality on dynamic social gesture processing: An fMRI study. AB - This fMRI study aimed at investigating how differences in personality traits affect the processing of dynamic and natural gestures containing social versus nonsocial intent. We predicted that while processing gestures with social intent extraversion would be associated with increased activity within the reticulothalamic-cortical arousal system (RTCS), while neuroticism would be associated with increased activity in emotion processing circuits. The obtained findings partly support our hypotheses. We found a positive correlation between bilateral thalamic activity and extraversion scores while participants viewed social (versus nonsocial) gestures. For neuroticism, the data revealed a more complex activation pattern. Activity in the bilateral frontal operculum and anterior insula, extending into bilateral putamen and right amygdala, was moderated as a function of actor-orientation (i.e., first versus third-person engagement) and face-visibility (actor faces visible versus blurred). Our findings point to the existence of factors other than emotional valence that can influence social gesture processing in particular, and social cognitive affective processing in general, as a function of personality. PMID- 26541445 TI - [Analysis of morbidity and mortality after gastrectomy in 238 patients]. PMID- 26541447 TI - [Complication management in minimally invasive surgery]. PMID- 26541448 TI - [Specific complications of minimally invasive surgery]. AB - Minimally invasive surgery (MIS) is fundamentally different from open surgery regarding positioning of the patient, access routes and instrumentation. Each of these aspects is associated with its own specific morbidity, such as positioning related complications, trocar-induced lesions, hypercapnia-associated phenomena and thermal damage. The growing experience of surgeons and technological progress have increased patient safety to a maximum and have resulted in an impressive spread of MIS in the various fields of surgery including the most common, such as cholecystectomy and hernia repair and special fields, such as bariatric, thoracic and oncological surgery. This narrative review summarizes the current knowledge on the inherent complications of MIS. PMID- 26541450 TI - [Not Available]. PMID- 26541449 TI - [Characteristics of postoperative peritonitis]. AB - Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity. PMID- 26541451 TI - [Vascular reconstruction in visceral transplantation surgery]. AB - Vascular reconstruction is obligatory in transplantation surgery. A differentiation is made between routine vascular reconstructions, which are required for all solid organ transplantations and special cases. Because of the shortage of organs it is often necessary to use organs with complex anatomical vascular prerequisites, which requires high vascular surgical expertise for individualized reconstruction. Non-routine reconstructions are often also necessary on the side of the recipient. This review article presents both the routine and exceptional types of reconstruction. PMID- 26541452 TI - Enthesitis of lumbar spinal ligaments in clinically suspected spondyloarthritis: value of gadolinium-enhanced MR images in comparison to STIR. AB - OBJECTIVE: To compare detection of spinal ligament enthesitis between gadolinium enhanced fat-saturated T1-weighted gadolinium-enhanced fat-saturated T1-weighted (T1+Gd) and STIR sequences in patients with suspected spondyloarthritis. MATERIALS AND METHODS: Sixty-eight patients (37 males, 42 +/- 14 years) with a sacroiliac-joint (SIJ) and lumbar spine MRI for suspected spondyloarthritis were prospectively included. Sagittal T1+Gd and STIR images of the lumbar spine were assessed by two readers for enthesitis of interspinous/supraspinous ligaments, and for capsulitis of facet-joints between T12-S1. Patients' MRI were grouped according to ASAS (Assessment of SpondyloArthritis international Society) criteria in positive (group A) or negative (group B) SIJs. Enthesitis/capsulitis were compared between groups. Interreader agreement was assessed. RESULTS: Enthesitis/capsulitis per patient was statistically significantly more frequent with T1+Gd compared to STIR (p <= 0.007), except for interspinous ligaments for reader 1 (p = 0.455). Interspinous enthesitis, supraspinous enthesitis, and capsulitis were present with T1+Gd(STIR) in 64.7 %(72.1 %), 60.3 %(17.7 %), and 61.8 %(29.4 %) for reader 1, and 51.5 %(41.2 %), 45.6 %(7.4 %), and 91.2 %(45.5 %) for reader 2. There were 76.5 %(52/68) patients in group A and 23.5 %(16/68) in group B. Total number of enthesitis/capsulitis on T1+Gd was statistically significantly higher in group A than B (4.96 vs. 2.94, p = 0.026; 8.12 vs. 5.25, p = 0.041 for reader 1 and 2, respectively). Interreader agreement showed mixed results for interspinous/supraspinous/capsulitis but was higher on T1+Gd (ICC = 0.838/0.783/0.367; p <= 0.001) compared to STIR (ICC = 0.652/0.298/0.224; p <= 0.032). CONCLUSION: In patients with suspected spondyloarthritis, enthesitis/capsulitis in the lumbar spine are common findings and more frequently/reliably detected with T1+Gd than STIR. In patients with positive SIJ MRI, the total number of enthesitis/capsulitis in T1+Gd was higher compared to patients with negative SIJ-MRI. PMID- 26541453 TI - Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. AB - Traditional schizophrenia pharmacotherapy remains a subjective trial and error process involving administration, titration and switching of drugs multiple times until an adequate response is achieved. Despite this time-consuming and costly process, not all patients show an adequate response to treatment. As a consequence, relapse is a common occurrence and early intervention is hampered. Here, we have attempted to identify candidate blood biomarkers associated with drug response in 121 initially antipsychotic-free recent-onset schizophrenia patients treated with widely-used antipsychotics, namely olanzapine (n=40), quetiapine (n=23), risperidone (n=30) and a mixture of these drugs (n=28). Patients were recruited and investigated as two separate cohorts to allow biomarker validation. Data analysis showed the most significant relationship between pre-treatment levels of heart-type fatty acid binding protein (H-FABP) and response to olanzapine (p=0.008, F=8.6, beta=70.4 in the discovery cohort and p=0.003, F=15.2, beta=24.4 in the validation cohort, adjusted for relevant confounding variables). In a functional follow-up analysis of this finding, we tested an independent cohort of 10 patients treated with olanzapine and found that baseline levels of plasma H-FABP and expression of the binding partner for H FABP, fatty acid translocase (CD36), on monocytes predicted the reduction of psychotic symptoms (p=0.040, F=6.0, beta=116.3 and p=0.012, F=11.9, beta=-0.0054, respectively). We also identified a set of serum molecules changed after treatment with antipsychotic medication, in particular olanzapine. These molecules are predominantly involved in cellular development and metabolism. Taken together, our findings suggest an association between biomarkers involved in fatty acid metabolism and response to olanzapine, while other proteins may serve as surrogate markers associated with drug efficacy and side effects. PMID- 26541454 TI - A human monoclonal IgE antibody that binds to MGL_1304, a major allergen in human sweat, without activation of mast cells and basophils. AB - MGL_1304, a major allergen in human sweat for patients with atopic dermatitis and/or cholinergic urticaria, is secreted from Malassezia globosa on human skin. The amounts of MGL_1304 and IgE against MGL_1304 are evaluated by the histamine release test using basophils or mast cells sensitized with serum containing IgE against MGL_1304, and enzyme linked sorbent assay (ELISA) using MGL_1304 and anti MGL_1304 antibodies. Here, we identified a human monoclonal IgE (ABS-IgE) that binds to the high affinity IgE receptor (FcepsilonRI) and MGL_1304 with high affinity (KD = 1.99 nM) but does not release histamine from basophils and mast cells. An ELISA using ABS-IgE as a standard IgE revealed that the amount of IgE against MGL_1304 (1000 U/ml) in the standard sera of patients with AD, employed in our previous report, is 32 ng/ml. A sandwich ELISA using ABS-IgE as a detection antibody showed approximately 10 times lower detection limit for MGL_1304 than ELISA in which MGL_1304 is directly bound to an ELISA plate. Moreover, ABS-IgE prevented histamine release from mast cells and basophils by neutralizing MGL_1304 not only in a free form in solution, but also on FcepsilonRI expressed on the cell surface without cell activation. ABS-IgE may be used both to quantify the amount of MGL_1304 and anti-MGL_1304 IgE, and possibly for the treatment of diseases caused/aggravated by type I allergy to MGL_1304. PMID- 26541455 TI - MiR-143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells. AB - Therapeutic applications of microRNAs (miRNAs) in chemotherapy were confirmed to be valuable, but there is rare to identify their specific roles and functions in shikonin treatment toward tumors. Here, for the first time, we reported that miR 143 played a critical role in the antitumor activity of shikonin in glioblastoma stem cells (GSCs). The results showed that the expression of miR-143 was downregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly enhanced the inhibitory effect of shikonin toward GSCs on cell viability. Besides, miR-143 overexpression caused a significant increase in the apoptotic fraction and made apoptosis occur earlier. Further investigation identified that BAG3, an apoptotic regulator, was a functional target of miR-143 in shikonin treated GSCs. The expression of BAG3 was upregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly reversed the high expression of BAG3 in shikonin treated GSCs. Moreover, it was confirmed that the enhanced cytotoxicity of shikonin by miR-143 overexpression was reversed by BAG3 overexpression both in vitro and in vivo, suggesting that the enhanced tumor suppressive effects by miR-143 overexpression was at least partly through the regulation of BAG3. Taken together, for the first time, our results demonstrate that miR-143 could enhance the antitumor activity of shikonin toward GSCs through reducing BAG3 expression, which may provide a novel therapeutic strategy for enhancing the treatment efficacy of shikonin toward GSCs. PMID- 26541456 TI - Involvement of periostin-sclerostin-Wnt/beta-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin. AB - Periostin has an essential role in mechanotransduction in bone. Naringin, a natural flavonoid, has been evidenced for its osteoprotective role in osteoporosis, while its mechanism is far from clear. Here we show that down regulation of periostin, and up-regulation of its downstream sclerostin and inactivation of Wnt/beta-catenin signaling were implicated in neurectomy-induced bone loss. Naringin could up-regulate periostin and prevent neurectomy-induced deterioration of BMD, trabecular microstructure and bone mechanical characteristics. In conclusion, naringin could prevent progress of disuse osteoporosis in rats, which may be mediated by increased periostin expression and subsequently inhibition of sclerostin and activation of Wnt/beta-catenin signaling pathways. PMID- 26541457 TI - Innovations in steelmaking technology and hidden phosphorus flows. AB - This article will outline the historical transition in the flow of phosphorus in steelmaking technology, and examine the current and future phosphorus flow in steel production and the peripheral steelmaking processes. History provides many instances of innovative changes in steelmaking processes driven by various issues associated with raw materials which emerged over time, such as supply, quality and cost issues. The major steel countries with a long history, including Sweden and Japan, have shown flexibility in their ability to adapt to the changes in the value of resources and geopolitical conditions over times, and have enacted survival resource utilization measures over many centuries, leading to improvements in their respective steelmaking processes. Considering these success stories, it stands to reason that the ideal state of steelmaking is one with a clear stance with regard to resource policy. PMID- 26541458 TI - Image-Guided Nontargeted Renal Biopsies Performed by Radiology-Trained Nurse Practitioners: A Safe Practice Model. PMID- 26541462 TI - Amyloid Fibres: Inert End-Stage Aggregates or Key Players in Disease? AB - The formation of amyloid fibres is a hallmark of amyloid disorders. Nevertheless, the lack of correlation between fibre load and disease as observed, for example, in Alzheimer's disease, means that fibres are considered secondary contributors to the onset of cellular dysfunction. Instead, soluble intermediates of amyloid assembly are often described as the agents of toxicity. Here, we discuss recent experimental discoveries which suggest that amyloid fibres should be considered as disease-relevant species that can mediate a range of pathological processes. These include disruption of biological membranes, secondary nucleation, amyloid aggregate transmission, and the disruption of protein homeostasis (proteostasis). Thus, a greater understanding of amyloid fibre biology could enhance prospects of developing therapeutic interventions against this devastating class of protein misfolding disorders. PMID- 26541461 TI - Redefining the BH3 Death Domain as a 'Short Linear Motif'. AB - B cell lymphoma-2 (BCL-2)-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3 containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence the BCL-2 family has expanded to include a nebulous group of nonhomologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs) and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions. PMID- 26541463 TI - Salinimicrobium soli sp. nov., isolated from soil of reclaimed land. AB - A Gram-stain-negative, facultatively anaerobic, non-gliding, rod-shaped bacterial strain, designated CAU 1287T, was isolated from a soil sample of reclaimed land and its taxonomic position was investigated using a polyphasic approach. Strain CAU 1287T grew optimally at 30 degrees C, at pH 5.5 and in the presence of up to 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1287T formed a distinct lineage within the genus Salinimicrobium and shared the highest 16S rRNA gene sequence similarity of 98.0 % with Salinimicrobium gaetbulicola KCTC 23579T. Similar to other species of the genus Salinimicrobium, menaquinone-6 (MK-6) was the only isoprenoid quinone and iso C15:0 and anteiso-C15:0 were the major cellular fatty acid detected in strain CAU 1287T. The polar lipid pattern of strain CAU 1287T consisted of phosphatidylethanolamine and various unidentified lipids including three aminolipids, one aminophospholipid, one phosphoglycolipid, one glycolipid, and three lipids. The DNA G+C content of CAU 1287T was 43.4 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain CAU 1287T represents a novel species of the genus Salinimicrobium, for which the name Salinimicrobium soli sp. nov. is proposed. The type strain is CAU 1287T ( = KCTC 32163T = CCUG 64794T). PMID- 26541464 TI - Formulation and optimization of idarubicin thermosensitive liposomes provides ultrafast triggered release at mild hyperthermia and improves tumor response. AB - Drug delivery through thermosensitive liposomes (TSL) in combination with hyperthermia (HT) has shown great potential. HT can be applied locally forcing TSL to release their content in the heated tumor resulting in high peak concentrations. To perform optimally the drug is ideally released fast (seconds) and taken up rapidly by tumor cells. The aim of this study was to develop a novel thermosensitive liposome formulation of the anthracycline idarubicin (IDA-TSL). The hydrophobicity of idarubicin may improve its release from liposomes and subsequently rapid cellular uptake when combined mild hyperthermia. Here, we investigated a series of parameters to optimize IDA-TSL formulation. The results show that the optimal formulation for IDA-TSL is DPPC/DSPC/DSPE-PEG (6/3.5/0.5 mol%), with ammonium EDTA of 6.5 pH as loading buffer and a size of ~85 nm. In vitro studies demonstrated minimal leakage of ~20% in FCS at 37 degrees C for 1h, while an ultrafast and complete triggered release of IDA was observed at 42 degrees C. On tumor cells IDA-TSL showed comparable cytotoxicity to free IDA at 42 degrees C, but low cytotoxicity at 37 degrees C. Intravital microscopy imaging demonstrated an efficient in vivo intravascular triggered drug release of IDA-TSL under mild hyperthermia, and a subsequent massive IDA uptake by tumor cells. In animal efficacy studies, IDA-TSL plus mild HT demonstrated prominent tumor growth inhibition and superior survival rate over free IDA with HT or a clinically used Doxil treatment. These results suggest beneficial potential of IDA-TSL combined with local mild HT. PMID- 26541465 TI - Teaching of Independent Exercises for Prehabilitation in Breast Cancer. AB - We attempted to determine the feasibility of studying prehabilitation exercises to improve shoulder pain and abduction range of motion (ROM) after breast cancer surgery. We evaluated methods of exercise teaching and assessed effect on postsurgical seroma formation. This was a feasibility study with two non-blinded groups of subjects randomized by timing of appointment. This single-site study was performed at an academic tertiary medical center. Sixty cancer patients were randomly assigned to either group 1, in-person teaching arm, n = 36, or group 2, video-only teaching arm, n = 24. Forty-five patients completed the study. Shoulder exercises were assigned to both groups 1 month prior to surgery during evaluation. Group 1 received in-person instruction on exercises, plus an information sheet with exercises and a link to an online video. Group 2 received only the information sheet with exercises and a link to the online video. The primary outcomes considered are as follows: exercise compliance, shoulder pain (via visual analog scale), shoulder abduction ROM (via goniometer), and presence or absence of seroma. Seventy-six percent of study patients chose to exercise. There was no difference in exercise compliance between in-person teaching versus video teaching (75 %, 24/32 vs. 77 %, 10/13, OR = 1.03). Sixty-six of patients (20/30) lost greater than 10 degrees shoulder abduction ROM at 1 month post surgery. Twenty-nine of patients (9/31) had worse shoulder pain than baseline at 1 month post surgery (24 %, 6/25 exercisers, and 50 %, 3/6 non-exercisers). Fifteen percent of patients (4/27) had worse shoulder pain than baseline at 3 months post surgery (8 %, 2/23 exercisers, and 100 %, 2/2 non-exercisers). Prehabilitation exercise program inferred no additional risk of seroma formation (Exercisers 21 %, 7/33 vs. non-exercisers 22 %, 2/9, OR = 0.94). Our subjects were able to perform three exercises independently in the preoperative period. A high-quality randomized controlled trial is necessary to assess the appropriate timing and efficacy of this intervention. PMID- 26541466 TI - Affinity reagents for studying histone modifications & guidelines for their quality control. AB - Histone post-translational modifications (PTMs) have pivotal functions in many chromatin processes, which makes their detection and characterization an imperative in chromatin biology. The established approaches for histone PTM characterization are generally based on affinity reagents specific for modified histone tails such as antibodies and, most recently, recombinant reading domains. Hence, the proper performance of these reagents is a critical precondition for the validity of the generated experimental data. In this review, we evaluate and update the quality criteria for assessment of the binding specificity of histone PTM affinity reagents. In addition, we discuss in detail the advantages and pitfalls of using antibodies and recombinant reading domains in chromatin biology research. Reading domains provide key advantages, such as consistent quality and recombinant production, but the future will tell if this emerging technology keeps its promises. PMID- 26541467 TI - Study on electronic structures and properties of neutral and charged arsenic sulfides [As n S3 ((-1,0,+1)), n =1-6] with the Gaussian-3 scheme. AB - The structures and energies of neutral and charged arsenic sulfides As n S3 (( 1,0,+1)) (n = 1-6) were studied systematically with the G3 method. The ground state structures of these species are reported. The ground-state structures of As n S3 with n >= 4 can be considered as resulting from the replacement of an As atom of the ground-state structure of neutral As n+1S2 by an S atom. In neutral As n S3, the character of sulfur bonding is edge-bridging. The ground-state structures of anion As n S3 (-) sometimes differ from their corresponding neutral structures. In such case, they exhibit a terminal sulfur atom. The ground-state structures of cationic As n S3 (+) are also sometimes different from the corresponding neutral ones. There, sulfur bonding can exhibit face-capping and arsenic can be four-fold coordinated. The potential energy surfaces of As4S3 (+) and As5S3 (+) are very flat and co-existence of various isomers of As4S3 (+) and As5S3 (+) is possible. Reliable adiabatic electron affinities (AEAs) and adiabatic ionization potentials (AIPs) of As n S3 are predicted. There are odd even alternations in both AEAs and AIPs as a function of size. In addition, the reliable vertical detachment energies (VDEs) and vertical ionization potentials (VIPs) are presented. The dissociation energies (DEs) of S (and/or its ion S(( /+))) from As n S3 species and their ions were calculated to examine relative stabilities. The hardnesses and HOMO-LUMO gaps of As n S3 (n = 1-6) were evaluated and used to discuss relative chemical reactivity. PMID- 26541468 TI - Pressure-induced phase transition in CrO2. AB - The ab initio constant pressure molecular dynamics technique and density functional theory with generalized gradient approximation (GGA) was used to study the pressure-induced phase transition of CrO2. The phase transition of the rutile (P42/mnm) to the orthorhombic CaCl2 (Pnnm) structure at 30 GPa was determined successfully in a constant pressure simulation. This phase transition was analyzed from total energy calculations and, from the enthalpy calculation, occurred at around 17 GPa. Structural properties such as bulk modules, lattice parameters and phase transition were compared with experimental results. The phase transition at 12 +/- 3 GPa was in good agreement with experimental results, as was the phase transition from the orthorhombic CaCl2 (Pnnm) to the monoclinic (P21/c) structure also found at 35 GPa. PMID- 26541469 TI - Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia with Ceftaroline Fosamil in a Patient with Inhalational Thermal Injury. AB - A 48-year-old female, who was found unresponsive and suffered inhalation injury secondary to a house fire, was transferred to our burn center for definitive treatment. Post tracheostomy, the patient became febrile and tachycardic. On hospital day (HD) 5, the patient expressed thick yellow secretions during suctioning and diffuse rhonchi was noted on physical exam. Blood cultures and a culture from the broncheo-alvelolar lavage grew Gram-positive cocci in clusters and the patient was started on empiric vancomycin. Despite aggressive vancomycin dosing (1750 mg intravenously every 6 h), the patient's status continued to deteriorate. The organism was identified as methicillin-resistant Staphylococcus aureus (MRSA) with a vancomycin minimum inhibitory concentration (MIC) of 2 mg/L. Based on the potential for drug-drug interactions with linezolid, the patient was started on ceftaroline fosamil (MIC = 0.5 mg/L) 600 mg intravenously every 8 h with a prolonged 2-h infusion to anticipate suboptimal concentrations secondary to thermal burn injury. Post change in antibiotic therapy, a rapid clinical improvement was observed with the patient becoming afebrile at 48 h after initiation of ceftaroline. The patient completed a total of 14 days of ceftaroline therapy and was subsequently weaned from the ventilator on HD 22 and decannulated 2 days later. To our knowledge, this is the first report of the use of ceftaroline for the treatment of MRSA pneumonia in a patient with thermal injury. PMID- 26541470 TI - Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-alpha2. AB - Interferon (IFN)-alpha2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-alpha2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-alpha2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN alpha2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represent one of the most used models for studying mechanisms involved in neurotoxicity or neuroprotection. To test our hypothesis we have characterized the metabolic signature of live SH-SY5Y, and their conditioned media, after 24 and 72 h of exposure to vehicle or IFN-alpha2 (100 ng/ml) by using High Resolution-Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) spectroscopy. Our results revealed that 1) the use of HR MAS NMR is ideally suitable for the characterization of the metabolic profile of live cells and their conditioned media without extraction procedures; and 2) a 72 h exposure to IFN-alpha2 increases the level of metabolites involved in maintaining energetic (including creatine and lactate) and osmotic (such as myo inositol, scyllo-inositol, taurine and glycerophosphorylcholine) balances in neuron-like cells and of metabolic waste products (namely lactate, ethanol and acetate), glycine and glutamine in their growth media. These results may contribute to gain more knowledge about the IFN-alpha2 induced effect on the brain and support the interpretation of magnetic resonance spectroscopy studies performed in humans. PMID- 26541471 TI - Survival outcomes of 220 consecutive patients with three-staged thoracoscopic esophagectomy. AB - Patients with thoracic esophageal cancer are often treated by minimally invasive esophagectomy. However, the long-term survival benefits of minimally invasive esophagectomy remain unclear. Two approaches are available for thoracoscopic surgery: one with the patient in the left lateral decubitus position (LLDP), and the other with the patient in the prone position (PP). We investigated the survival benefit of thoracoscopic esophagectomy according to the tumor stage and patient position during the thoracoscopic procedure. We reviewed the records of 220 consecutive patients with esophageal cancer treated from 1998 to 2012. In total, 146 and 74 patients were treated with thoracoscopic esophagectomy in the LLDP and PP, respectively. No patients were initially proposed to be candidates for esophagectomy by thoracotomy during the study period. Data collection was performed with a focus on survival and recurrent disease. Among all the 220 patients, the overall 5-year survival rates were 83.7%, 74.1%, 45.5%, 78.6%, 44.2%, 29.4% and 24.3% in the patients with pStage IA, IB, IIA, IIB, IIIA, IIIB and IIIC disease, respectively. Despite the greater number of dissected mediastinal lymph nodes in the PP procedure, there were no significant differences in the survival curves between the LLDP and PP procedures. The long term results of thoracoscopic esophagectomy are comparable and acceptable. The PP procedure was not confirmed to offer a superior survival benefit to the LLDP procedure in this retrospective study. PMID- 26541472 TI - Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy. AB - PURPOSE: Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. MATERIALS AND METHODS: Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). RESULTS: Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). CONCLUSION: Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca. PMID- 26541473 TI - Complete genome sequence of the siphovirus Roseophage RDJLPhi 2 infecting Roseobacter denitrificans OCh114. AB - RDJLPhi2, a lytic phage that infects the marine bacterium Roseobacter denitrificans OCh114, one of the model organisms of the Roseobacter clade, was isolated. Here we report the overall genome architecture of RDJLPhi2. Morphological and genome analysis revealed that RDJLPhi2 is a siphovirus with a 63.5 kb genome that contains 76 putative gene products. PMID- 26541474 TI - Functional characterization of the hGRalphaT556I causing Chrousos syndrome. AB - BACKGROUND: Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case of Chrousos syndrome has been reported in a patient with adrenal incidentaloma, who harboured a heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand-binding domain of the receptor. OBJECTIVE: To delineate the molecular mechanisms through which the mutant receptor hGRalphaT556I causes Chrousos syndrome. DESIGN AND RESULTS: Compared with the wild-type receptor, the mutant receptor hGRalphaT556I demonstrated 50% reduction in its ability to transactivate glucocorticoid-responsive genes and in the affinity for the ligand, 30% increase in the ability to transrepress the nuclear factor-kappaB-target genes and a 3,4-fold delay in the cytoplasmic-to-nuclear translocation. The mutant receptor hGRalphaT556I did not exert a dominant negative effect upon the hGRalpha-mediated transcriptional activity; it preserved its ability to bind to DNA and interacted with the glucocorticoid receptor-interacting protein 1 coactivator mostly through its activation function-1 domain. Structural biology studies revealed that the T556I mutation caused disruption of the hydrogen bond formed by the T556 with the =O group of P637 backbone, which resulted in a significant relocation of the P637-bearing loop. This conformational alteration affected the local 3D arrangement of the receptor and hence the electrostatic surface of the region. CONCLUSIONS: The hGRalphaT556I causes Chrousos syndrome by impairing multiple steps of the glucocorticoid signal transduction pathway. PMID- 26541475 TI - Single-Step Functionalization and Exfoliation of Graphene with Polymers under Mild Conditions. AB - The simultaneous polymer functionalization and exfoliation of graphene sheets by using mild bath sonication and heat treatment at low temperature is described. In particular, free-radical polymerization of three different vinyl monomers takes place in the presence of graphite flakes. The polymerization procedure leads to the exfoliation of graphene sheets and at the same time the growing polymer chains are attached onto the graphene lattice, which gives solubility and stability to the final graphene-based hybrid material. The polymer-functionalized graphene sheets possess fewer defects as compared with previously reported polymer-functionalized graphene. The success of the covalent functionalization and exfoliation of graphene was confirmed by using a variety of complementary spectroscopic, thermal, and microscopy techniques, including Raman, IR and UV/Vis spectroscopy, thermogravimetric analysis, and transmission electron microscopy. PMID- 26541476 TI - Childhood Sexual Abuse Moderates the Relationship Between Obesity and Mental Health in Low-Income Women. AB - We examined whether a history of self-reported childhood sexual abuse (CSA) moderates the relationship between obesity and mental health symptoms (depression, anxiety, and posttraumatic stress disorder) in an ethnically diverse sample of low-income women. A community sample of 186 women completed self-report measures and had their weight and height measured. Body mass index and CSA had an interactive effect on all mental health measures, such that obese women with a CSA history reported substantially higher levels of all symptoms. These results give greater specificity to the obesity-mental health link reported in previous studies and provide possible directions for targeted intervention. PMID- 26541477 TI - Mechanisms underlying the activity-dependent regulation of locomotor network performance by the Na+ pump. AB - Activity-dependent modification of neural network output usually results from changes in neurotransmitter release and/or membrane conductance. In Xenopus frog tadpoles, spinal locomotor network output is adapted by an ultraslow afterhyperpolarization (usAHP) mediated by an increase in Na(+) pump current. Here we systematically explore how the interval between two swimming episodes affects the second episode, which is shorter and slower than the first episode. We find the firing reliability of spinal rhythmic neurons to be lower in the second episode, except for excitatory descending interneurons (dINs). The sodium/proton antiporter, monensin, which potentiates Na(+) pump function, induced similar effects to short inter-swim intervals. A usAHP induced by supra threshold pulses reduced neuronal firing reliability during swimming. It also increased the threshold current for spiking and introduced a delay to the first spike in a train, without reducing subsequent firing frequency. This delay was abolished by ouabain or zero K(+) saline, which eliminate the usAHP. We present evidence for an A-type K(+) current in spinal CPG neurons which is inactivated by depolarization and de-inactivated by hyperpolarization, and accounts for the prolonged delay. We conclude that the usAHP attenuates neuronal responses to excitatory network inputs by both membrane hyperpolarization and enhanced de inactivation of an A-current. PMID- 26541478 TI - Surgical anatomy of oropharynx and supraglottic larynx for transoral robotic surgery. AB - Traditional external surgical approaches have been used for the surgical management of the oropharyngeal and laryngeal tumors. Trans-oral robotic surgery allows surgeon to operate oropharyngeal and supraglottic tumors through the mouth with preservation of functions. The surgeons must be knowledgeable about the anatomy of the oral cavity and oropharynx medial to lateral perspective. In this article, we will describe the relevant inside out surgical anatomy and its clinical implications for trans-oral robotic surgery. PMID- 26541479 TI - Epidural analgesia is superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction. AB - BACKGROUND AND PURPOSE: Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction. PATIENTS AND METHODS: Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period. RESULTS: The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p = 0.01; VAS-OBS: 5.2, p = 0.02) and the placebo group (r-FLACC: 5.2, p = 0.01; VAS-OBS: 6.5, p < 0.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p < 0.001). INTERPRETATION: Epidural analgesia is superior to local infiltration analgesia for early postoperative pain management in children with cerebral palsy who undergo unilateral hip reconstruction. PMID- 26541480 TI - Modular Assembly of Allosteric MEK Inhibitor Structural Elements Unravels Potency and Feedback-Modulation Handles. AB - Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide headgroup with inverse sulfonamides resulted in the identification of new MEK inhibitors with at least 10-fold higher cellular potency against K-Ras-mutated tumor cells. A selected inhibitor from this new series retained the favorable pharmacokinetic profile of its predecessor in rodent and non-rodent species and displayed significant in vivo efficacy at once-daily oral doses of 0.25-1 mg kg( 1) in a K-Ras-mutated xenograft model. The brain penetration potential of this analogue was significantly attenuated relative to PD325901. In a second series, the central fluorophenyl core was replaced by a pyridine moiety which gave rise to a similar boost in cellular potency. Most notably, analogues from this second series do not show MEK feedback phosphorylation in K-Ras-mutated A549 cells. Our results complement recent reports on the structural intricacies of MEK-Raf feedback interactions. PMID- 26541483 TI - The flagellum in bacterial pathogens: For motility and a whole lot more. AB - The bacterial flagellum is an amazingly complex molecular machine with a diversity of roles in pathogenesis including reaching the optimal host site, colonization or invasion, maintenance at the infection site, and post-infection dispersal. Multi-megadalton flagellar motors self-assemble across the cell wall to form a reversible rotary motor that spins a helical propeller - the flagellum itself - to drive the motility of diverse bacterial pathogens. The flagellar motor responds to the chemoreceptor system to redirect swimming toward beneficial environments, thus enabling flagellated pathogens to seek out their site of infection. At their target site, additional roles of surface swimming and mechanosensing are mediated by flagella to trigger pathogenesis. Yet while these motility-related functions have long been recognized as virulence factors in bacteria, many bacteria have capitalized upon flagellar structure and function by adapting it to roles in other stages of the infection process. Once at their target site, the flagellum can assist adherence to surfaces, differentiation into biofilms, secretion of effector molecules, further penetration through tissue structures, or in activating phagocytosis to gain entry into eukaryotic cells. Next, upon onset of infection, flagellar expression must be adapted to deal with the host's immune system defenses, either by reduced or altered expression or by flagellar structural modification. Finally, after a successful growth phase on or inside a host, dispersal to new infection sites is often flagellar motility mediated. Examining examples of all these processes from different bacterial pathogens, it quickly becomes clear that the flagellum is involved in bacterial pathogenesis for motility and a whole lot more. PMID- 26541484 TI - Hypoglycemia: the dangerous side of great control. PMID- 26541485 TI - REMOVED: Hypoglycemia. PMID- 26541482 TI - The central role of hypothalamic inflammation in the acute illness response and cachexia. AB - When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. PMID- 26541486 TI - Acute management and outcomes of patients with diabetes mellitus presenting to Canadian emergency departments with hypoglycemia. AB - OBJECTIVES: This retrospective chart audit examined the demographics, investigations, management and outcomes of adult patients with diabetes mellitus presenting to Canadian emergency departments (EDs). METHODS: All sites conducted a search of their electronic medical records using International Classification of Diseases, Tenth Revision, codes to identify ED visits for hypoglycemia between 2008 and 2010. Patient characteristics, demographics, ED management, ED resources and outcome are reported. RESULTS: A total of 1039 patients over the age of 17 years were included in the study; 347 (33.4%) were classified as type 1 diabetes and 692 (66.6%) were classified as type 2 diabetes. Type 2 diabetes patients were significantly older (73 vs. 49 years; p<0.0001) and had more chronic conditions recorded on their chart (all p<0.001). Most subjects arrived by ambulance, and triage scores revealed severe presentations in 39% of cases. Treatments for hypoglycemia were common (75.7%) during prehospital transport; 38.5% received intravenous glucose and 40.1% received glucagon. Hypoglycemia treatments in the ED included oral (76.8%), intravenous (29.6%) and continuous infusion (27.7%) of glucose. Diagnostic testing (81.9%) commonly included electrocardiograms (51.9%), chest radiography (37.5%) and head computed tomography scans (14.5%). Most patients (73.5%) were discharged; however, more subjects with type 2 diabetes required admission (30.3 vs. 8.8%). Discharge instructions were documented in only 55.5% of patients, and referral to diabetes services occurred in fewer than 20% of cases. Considerable variation existed in the management of hypoglycemia across EDs. CONCLUSIONS: Patients with diabetes presenting to an ED with hypoglycemia consume considerable healthcare resources, and practice variation exists. Emergency departments should develop protocols for the management of hypoglycemia, with attention to discharge planning to reduce recurrence. PMID- 26541487 TI - Dosing irregularities and self-treated hypoglycemia in type 2 diabetes: results from the Canadian Cohort of an International Survey of Patients and Healthcare Professionals. AB - OBJECTIVE: Despite their importance in achieving good glycemic control, few real world data on insulin dosing irregularities and hypoglycemia are available. The multinational, online Global Attitude of Patients and Physicians (GAPP2) survey was conducted to address this situation. METHODS: Insulin-treated patients with type 2 diabetes and healthcare professionals (HCPs) who treat such patients were surveyed in an online cross-sectional study. This article summarizes findings from a sample of the online population in a Canadian cohort of 156 patients and 202 HCPs. RESULTS: A total of 156 patients completed the questionnaires; 26% reported experiencing a dosing irregularity (missed, mistimed or reduced a basal insulin dose) in the previous 30 days. Up to 60% reported risk for hypoglycemia as the reason for intentional dosing irregularities. Of all patients, 80% reported experiencing a self-treated hypoglycemic event, and 33% recalled having at least 1 event in the previous month. HCPs recorded similar levels of patient reported dosing irregularities. Over 90% indicated they recommended patients to temporarily reduce their insulin doses to deal with hypoglycemia. CONCLUSIONS: A sizeable minority of patients experienced dosing irregularities and self-treated hypoglycemia in this Canadian cohort. The data suggest that HCPs who completed the survey are aware of this and of the need to provide education and support for patients who regularly miss, mistime or reduce insulin doses. Although the desire to prevent hypoglycemic events is understandable and important, HCPs need to ensure fear of hypoglycemia does not compromise optimal diabetes management. PMID- 26541489 TI - The hypoglycemic risk of glyburide (glibenclamide) compared with modified-release gliclazide. AB - OBJECTIVES: The risk for hypoglycemia when taking glyburide compared with modified-release gliclazide remains to be established in older adults in routine care. We investigated the risk of a hospital encounter with hypoglycemia following a new prescription for glyburide compared with modified-release gliclazide. METHODS: In 2 population-based matched retrospective cohort studies in Ontario, Canada, between 2002 and 2011, we examined older adults who were newly prescribed glyburide or gliclazide as monotherapy or in the presence of metformin. Our primary outcome was a hospital encounter with hypoglycemia assessed within 90 days. RESULTS: The baseline characteristics between matched groups were similar. Initiating glyburide vs. gliclazide as monotherapy was associated with a higher risk for a hospital encounter with hypoglycemia (69 patients of 4374 taking glyburide [1.58%] vs. 8 patients of 4374 taking gliclazide [0.18%], absolute risk increase 1.40% [95% CI 1.01% to 1.79%], number needed to harm 71 [55 to 99], odds ratio 8.63 [95% CI 4.15 to 17.93], p<0.0001). Similar findings were noted when glyburide vs. gliclazide was initiated in the presence of metformin (110 patients of 8038 taking glyburide [1.37%] vs. 19 patients of 8038 taking gliclazide [0.24%], absolute risk increase 1.13% [95% CI 0.86% to 1.40%], number needed to harm 77 [71 to 116], odds ratio 6.06 [95% CI 3.68 to 9.97], p<0.0001). CONCLUSIONS: Glyburide was associated with a higher risk for hypoglycemia than modified-release gliclazide. The results of our studies may help to convince healthcare professionals who use glyburide to consider modified-release gliclazide as a safer alternative. PMID- 26541488 TI - Prospective assessment of hypoglycemia symptoms in children and adults with type 1 diabetes. AB - PURPOSE: To compare the characteristics of symptoms of hypoglycemia in children and in adults with type 1 diabetes. METHODS: Adults with diabetes and parents of children with diabetes who were participants were asked to call a phone system to report episodes of hypoglycemia (presence of symptoms and a blood glucose <4.0 mmol/L). For each episode, blood glucose reading and a scoring of 28 symptoms on a 7-point scale (1 = not present, 7 = very intense) were collected. RESULTS: Sixty six children (49.2% males, mean age = 12.1+/-2.4 years, mean age at diagnosis = 7.5+/-2.9 years) and 53 adults (41.2% males, mean age 38.7+/-14.5 years, mean age at diagnosis = 17.5+/-12.9 years) with type 1 diabetes participated. The most common symptoms in adults were hunger, sweating, trembling and weakness. The most common symptoms in children were weakness, trembling and hunger. The 2 most discriminating variables between children and adults were sleepiness and tiredness, which were more common in children (p<0.01). In a comparative factor analysis, 3 factors emerged: factor 1, autonomic and neuroglycopenic; factor 2, behavioural; and factor 3, general malaise. Factors 2 and 3 were significantly more common or intense in children than in adults; MANOVA: F(1, 113) = 6.72, p<0.05 and F(1, 113) = 4.64, p<0.05, respectively. CONCLUSIONS: Symptoms relating to behaviour and general malaise are more common in children than in adults with type 1 diabetes. The results of this study may assist providers in educating caregivers of children and patients with diabetes how to better recognize episodes of hypoglycemia. PMID- 26541490 TI - Two New Species of Homalometron (Digenea: Apocreadiidae) from Nearctic Freshwater Fundulids, Elucidation of the Life Cycle of H. cupuloris, and Molecular Phylogenetic Analysis of Some Congeners. AB - Two species of digeneans belonging in Homalometron are described from Nearctic freshwater fundulid fishes: Homalometron robisoni n. sp. is described from the Blackstripe Topminnow, Fundulus notatus, from Oklahoma and Homalometron frocioneae n. sp. is described from the Banded Killifish, Fundulus diaphanus, from New York. Homalometron robisoni n. sp. differs from all congeners by having vitelline follicles that extend into the forebody, a feature that necessitates altering the generic diagnosis for the genus. Homalometron frocioneae n. sp. may be distinguished from North and Middle American congeners by the position of the intestinal bifurcation (relatively more posterior in the forebody than in other species) and tegumental spine coverage on the body (spines are absent from the posterior body extremity and on most of the dorsal surface). Comparison of ribosomal DNA (ITS 1 and 2 regions, 5.8S gene, and partial fragment of 28S gene) from the 2 new species and some congeners from the Western Hemisphere provided evidence for the validity of the 2 new species and affirmed a close relationship between H. robisoni n. sp. and Homalometron pallidum. Comparison of ribosomal DNA from newly collected Homalometron spp. and larval stages of an apocreadiid from brackish water hydrobiid snails (cercariae in rediae in Littoridinops palustris and metacercariae in L. palustris and Amnicola limosa ) from a tidal river in Mississippi revealed that larval stages represented Homalometron cupuloris. A phylogeny based on Bayesian inference analysis using partial 28S rDNA gene fragments from 14 species of Homalometron (all from the Western Hemisphere) and 1 megaperine and rooted by a second megaperine was conducted and produced a strongly supported phylogram that estimates the interrelationships among species. The estimated phylogeny suggests that ecological factors such as salinity and food web interactions between species of Homalometron, intermediate hosts, and fishes drive coevolutionary forces influencing speciation within Homalometron. PMID- 26541493 TI - School readiness of children with language impairment: predicting literacy skills from pre-literacy and social-behavioural dimensions. AB - BACKGROUND: School readiness generally captures the notion that children do best when they arrive at formal schooling with a certain threshold of skill that will help them thrive in the classroom's academic and social milieu. AIMS: To examine the dimensionality of the construct of school readiness among children with language impairment (LI), as well as the extent to which these dimensions relate to children's end-of-kindergarten literacy skills. METHODS & PROCEDURES: Participants were 136 preschool-aged children with LI. Children were assessed on measures of pre-literacy, social, and behavioural skills in preschool and reading and spelling in kindergarten. OUTCOMES & RESULTS: Confirmatory factor analyses indicated that school readiness for this sample of children with LI is best characterized as two dimensions: pre-literacy and socio-emotional. Of the two dimensions, pre-literacy readiness was predictive of children's future performance in reading and spelling. CONCLUSIONS & IMPLICATIONS: The results further our theoretical understanding of the dimensions of school readiness, as well as our knowledge of how these skills are related among children with LI. Identifying domain-specific readiness skills that are predictive of kindergarten success can help to identify means of early assessment and targets for speech language intervention. PMID- 26541492 TI - Reduced in vivo hepatic proteome replacement rates but not cell proliferation rates predict maximum lifespan extension in mice. AB - Combating the social and economic consequences of a growing elderly population will require the identification of interventions that slow the development of age related diseases. Preserved cellular homeostasis and delayed aging have been previously linked to reduced cell proliferation and protein synthesis rates. To determine whether changes in these processes may contribute to or predict delayed aging in mammals, we measured cell proliferation rates and the synthesis and replacement rates (RRs) of over a hundred hepatic proteins in vivo in three different mouse models of extended maximum lifespan (maxLS): Snell Dwarf, calorie restricted (CR), and rapamycin (Rapa)-treated mice. Cell proliferation rates were not consistently reduced across the models. In contrast, reduced hepatic protein RRs (longer half-lives) were observed in all three models compared to controls. Intriguingly, the degree of mean hepatic protein RR reduction was significantly correlated with the degree of maxLS extension across the models and across different Rapa doses. Absolute rates of hepatic protein synthesis were reduced in Snell Dwarf and CR, but not Rapa-treated mice. Hepatic chaperone levels were unchanged or reduced and glutathione S-transferase synthesis was preserved or increased in all three models, suggesting a reduced demand for protein renewal, possibly due to reduced levels of unfolded or damaged proteins. These data demonstrate that maxLS extension in mammals is associated with improved hepatic proteome homeostasis, as reflected by a reduced demand for protein renewal, and that reduced hepatic protein RRs hold promise as an early biomarker and potential target for interventions that delay aging in mammals. PMID- 26541494 TI - Real-Time Quaking-Induced Conversion Analysis for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Korea. AB - BACKGROUND AND PURPOSE: The level of 14-3-3 protein in the cerebrospinal fluid (CSF) is increased in Creutzfeldt-Jakob disease (CJD) patients, which has led to it being used as a clinical biomarker for the ante-mortem diagnosis of human prion diseases. However, the specificity of the 14-3-3 protein is less reliable for CJD diagnosis. Newly developed assays including real-time quaking-induced conversion (RT-QuIC) have made it possible to detect the PrPSc-like abnormal prion isoform with a high sensitivity in animal and human specimens that might contain a minute amount of PrP(Sc) due to in vitro prion replication. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant human PrP to detect PrP(Sc) in the CSF of 81 patients with sporadic CJD (sCJD) in Korea. RESULTS: RT-QuIC analysis of the CSF samples based on the expression levels of 14 3-3 and total tau proteins revealed positivity in 62 of 81 sCJD patients (sensitivity of 76.5%) but no positive results in the 100 non-CJD patients. CONCLUSIONS: The sensitivity of the RT-QuIC in this study was similar to that in some previous reports, and the specificity of RT-QuIC was higher than that of 14 3-3 in CSF, suggesting that RT-QuIC analysis can complement the weakness of the specificity of 14-3-3 for the diagnosis of sCJD. These results indicate that RT QuIC might be very useful for the rapid and specific diagnosis of sCJD and provide a practical novel method for the ante-mortem diagnosis of human prion diseases. PMID- 26541495 TI - Adherence to Guidelines for Antithrombotic Therapy in Patients with Atrial Fibrillation According to CHADS2 Score before and after Stroke: A Multicenter Observational Study from Korea. AB - BACKGROUND AND PURPOSE: A substantial proportion of patients with atrial fibrillation (AF) are not treated optimally; however, the inappropriateness of drug therapy has never been evaluated before or after a stroke event. We investigated the adherence to guidelines for therapy in AF patients hospitalized with acute ischemic stroke (AIS) before stroke onset and at discharge, with the aim of identifying the factors associated with inappropriate therapy. METHODS: AIS patients with AF hospitalized within 7 days of onset were identified from a prospective nine-center stroke registry database. Two cohorts were defined: patients diagnosed with AF prior to the stroke event (admission cohort) and patients diagnosed with AF at discharge from hospital (discharge cohort). Any of the following conditions were regarded as nonadherence to guidelines in this study: use of anticoagulant or nonuse of antithrombotics with CHADS2 score=0, nonuse of antithrombotics with CHADS2 score=1, or nonuse of anticoagulant with CHADS2 score >=2. RESULTS: Overall, 406 patients were enrolled in the admission cohort and 518 in the discharge cohort. The rates of nonadherence before a stroke event and at discharge were 77.8% and 33.3%, respectively. These rates varied widely for both cohorts, with interhospital differences being statistically significant. Multivariable analysis revealed that old age, stroke history, and congestive heart failure were associated with nonadherence before stroke. At discharge, males, coronary heart disease, inappropriate antithrombotic use before stroke, and functional disability at discharge were associated with nonadherence. CONCLUSIONS: This study shows that antithrombotic use in AIS patients with AF might be not optimal before and after stroke in Korea. PMID- 26541496 TI - Ataxia with Oculomotor Apraxia Type 1 without Oculomotor Apraxia: A Case Report. PMID- 26541497 TI - Malignant Posterior Reversible Encephalopathy Syndrome: A Case of Posterior Irreversible Encephalopathy Syndrome. PMID- 26541498 TI - Immunoglobulin G4-Related Hypertrophic Pachymeningitis Mimicking Chiari Malformation. PMID- 26541499 TI - Heteroepitaxial Cu2O thin film solar cell on metallic substrates. AB - Heteroepitaxial, single-crystal-like Cu2O films on inexpensive, flexible, metallic substrates can potentially be used as absorber layers for fabrication of low-cost, high-performance, non-toxic, earth-abundant solar cells. Here, we report epitaxial growth of Cu2O films on low cost, flexible, textured metallic substrates. Cu2O films were deposited on the metallic templates via pulsed laser deposition under various processing conditions to study the influence of processing parameters on the structural and electronic properties of the films. It is found that pure, epitaxial Cu2O phase without any trace of CuO phase is only formed in a limited deposition window of P(O2) - temperature. The (00l) single-oriented, highly textured, Cu2O films deposited under optimum P(O2) - temperature conditions exhibit excellent electronic properties with carrier mobility in the range of 40-60 cm(2) V(-1) s(-1) and carrier concentration over 10(16) cm(-3). The power conversion efficiency of 1.65% is demonstrated from a proof-of-concept Cu2O solar cell based on epitaxial Cu2O film prepared on the textured metal substrate. PMID- 26541500 TI - Association between seminal plasma zinc level and asthenozoospermia: a meta analysis study. AB - Zinc is proposed to have an important role in the morphology, viability and motility of spermatozoa. There are inconsistent reports on the association between seminal plasma zinc concentration and male infertility. For this purpose, papers reporting the level of seminal zinc among asthenozoospermic groups were selected and used for further analysis. This meta-analysis of previous published studies was performed to obtain more precise information on the association between seminal plasma zinc and asthenozoospermia. Relevant studies for inclusion were identified after preliminary investigation of research papers published on electronic databases up to February 2015. Eight reports and 475 subjects were finally included in the meta-analysis. In the overall analysis, a statistically significant reduction in seminal plasma zinc concentrations was observed in asthenozoospermic infertile men. Random-effects method was used to evaluate the summary effect size due to the presence of significant heterogeneity. The effect of zinc on asthenozoospermia was significant (Hedge's G effect size = -0.506, 95% confidence interval (95% CI): -0.998 to -0.014, P = 0.044). Taken together, despite of significant statistical heterogeneity between studies, our findings were indicative of significant association between zinc concentration and asthenozoospermia. In conclusion, the meta-analysis suggests that seminal plasma zinc concentration is negatively associated with male infertility. PMID- 26541501 TI - Outcome expectations and associated treatment outcomes in motivational enhancement therapy delivered in English and Spanish. AB - BACKGROUND AND OBJECTIVES: The relationship between patients' baseline expectations regarding treatment outcome and actual outcomes has not been widely studied within the field of substance use disorders. We hypothesized that outcome expectations would be unrelated to outcomes in a study investigating motivational enhancement therapy delivered in English (MET-E) consistent with our earlier work, and conducted exploratory analyses in a separate study that investigated the same treatment delivered in Spanish (MET-S). METHODS: These secondary analyses compared patient outcome expectations and substance use treatment outcomes in two large, multisite randomized controlled clinical trials that evaluated three sessions of MET-E or MET-S. The MET-E sample included 461 participants and the MET-S sample included 405 participants. Outcome expectations were measured by a single item regarding expectations about abstinence prior to initiating treatment. RESULTS: Outcome expectations were strongly associated with most substance use outcomes in the MET-S trial (but not in MET-E), even after controlling for severity of substance use at baseline. In MET-S, those who indicated that they were "unsure" that they would achieve abstinence during treatment submitted a greater percentage of drug-positive urine toxicology screens during the treatment period than those who were 'sure' they would achieve abstinence (F = 18.83, p < .001). DISCUSSION AND CONCLUSIONS: Patients' outcome expectations regarding the likelihood of abstinence may be an important predictor of drug use treatment outcomes among Spanish-speakers, but not necessarily for English-speakers. SCIENTIFIC SIGNIFICANCE: Individual differences and cultural factors may play a role in the association between outcome expectations and treatment outcomes. PMID- 26541502 TI - Novel mode of liquid-phase microextraction: A magnetic stirrer as the extractant phase holder. AB - In the present study, a novel configuration of liquid-phase microextraction was proposed, in which a magnetic stirrer with a groove was used as the extractant phase holder. It was termed as magnetic stirrer liquid-phase microextraction. In this way, the stability of the organic solvent was much improved under high stirring speed; the extraction efficiency was enhanced due to the enormously enlarged contact area between the organic solvent and aqueous phase. The extraction performance of the magnetic stirrer liquid-phase microextraction was studied using chlorobenzenes as the probe analytes. A wide linearity range (20 pg/mL to 200 ng/mL) with a satisfactory linearity coefficient (r(2) > 0.998) was obtained. Limits of detection ranged from 9.0 to 12.0 pg/mL. Good reproducibility was achieved with intra- and inter-day relative standard deviations <4.8%. The proposed magnetic stirrer liquid-phase microextraction was simple, environmentally friendly and efficient; compared to single-drop microextraction, it had obvious advantages in terms of reproducibility and extraction efficiency. It is a promising miniaturized liquid-phase technology for real applications. PMID- 26541505 TI - Increased costs reduce reciprocal helping behaviour of humans in a virtual evacuation experiment. AB - Altruistic behaviour is widespread and highly developed in humans and can also be found in some animal species. It has been suggested that altruistic tendencies can depend on costs, benefits and context. Here, we investigate the changes in the occurrence of helping behaviour in a computer-based experiment that simulates an evacuation from a building exploring the effect of varying the cost to help. Our findings illuminate a number of key mechanistic aspects of human decision making about whether to help or not. In a novel situation where it is difficult to assess the risks associated with higher costs, we reproduce the finding that increasing costs reduce helping and find that the reduction in the frequency of helping behaviour is gradual rather than a sudden transition for a threshold cost level. Interestingly, younger and male participants were more likely to help. We provide potential explanations for this result relating to the nature of our experiment. Finally, we find no evidence that participants in our experiment plan ahead over two consecutive, inter-dependent helping opportunities when conducting cost-benefit trade-offs in spontaneous decisions. We discuss potential applications of our findings to research into decision-making during evacuations. PMID- 26541506 TI - Ligand-Controlled Synthesis of [3]- and [4]Cyclo-9,9-dimethyl-2,7-fluorenes through Triangle- and Square-Shaped Platinum Intermediates. AB - The syntheses of [3]- and [4]cyclo-9,9-dimethyl-2,7-fluorenes ([3] and [4]CFRs), cyclic trimer, and tetramers of 9,9-dimethyl-2,7-fluorene (FR), respectively, were achieved by the platinum-mediated assembly of FR units and subsequent reductive elimination of platinum. A triangle-shaped tris-platinum complex and a square-shaped tetra-platinum complex were obtained by changing the platinum ligand. The structure of the triangle complex was unambiguously determined by X ray crystallographic analysis. Reductive elimination of each complex gave [3] and [4]CFRs. Two rotamers of [3]CFR were sufficiently stable at room temperature and were separated by chromatography. The physical properties of the CFRs were also investigated theoretically and experimentally. PMID- 26541507 TI - Interactions of Molecules with cis and trans Double Bonds: A Theoretical Study of cis- and trans-2-Butene. AB - Noncovalent interactions of cis- and trans-2-butene, as the smallest model systems of molecules with cis and trans double bonds, were studied to find potential differences in interactions of these molecules. The study was performed using quantum chemical methods including very accurate CCSD(T)/CBS method. We studied parallel and displaced parallel interactions in 2-butene dimers, in butane dimers, and between 2-butene and saturated butane. The results show the trend that interactions of 2-butene with butane are the strongest, followed by interactions in butane dimers, whereas the interaction in 2-butene dimers are the weakest. The strongest calculated interaction energy is between trans-2-butene and butane, with a CCSD(T)/CBS energy of -2.80 kcal mol(-1) . Interactions in cis 2-butene dimers are stronger than interactions in trans-2-butene dimers. Interestingly, some of the interactions involving 2-butene are as strong as interactions in a benzene dimer. These insights into interactions of cis- and trans-2-butene can improve understanding of the properties and processes that involve molecules with cis and trans double bonds, such as fatty acids and polymers. PMID- 26541508 TI - Reversible superconductor-insulator transition in LiTi2O4 induced by Li-ion electrochemical reaction. AB - Transition metal oxides display various electronic and magnetic phases such as high-temperature superconductivity. Controlling such exotic properties by applying an external field is one of the biggest continuous challenges in condensed matter physics. Here, we demonstrate clear superconductor-insulator transition of LiTi2O4 films induced by Li-ion electrochemical reaction. A compact electrochemical cell of pseudo-Li-ion battery structure is formed with a superconducting LiTi2O4 film as an anode. Li content in the film is controlled by applying a constant redox voltage. An insulating state is achieved by Li-ion intercalation to the superconducting film by applying reduction potential. In contrast, the superconducting state is reproduced by applying oxidation potential to the Li-ion intercalated film. Moreover, superconducting transition temperature is also recovered after a number of cycles of Li-ion electrochemical reactions. This complete reversible transition originates in difference in potentials required for deintercalation of initially contained and electrochemically intercalated Li(+) ions. PMID- 26541509 TI - Effect of calcium phosphate addition to fluoride containing dental varnishes on enamel demineralization. AB - BACKGROUND: The aim of this study was to evaluate the ability of calcium phosphate and fluoride containing varnishes to inhibit enamel demineralization. METHODS: Six varnishes were selected for analysis: (1) Enamel Pro containing amorphous calcium phosphate; (2) Clinpro White containing functionalized tricalcium phosphate (fTCP); (3) MI Varnish containing casein phosphopeptide stabilized amorphous calcium phosphate (CPP-ACP); (4) Duraphat (first no added calcium control); (5) Profluorid (second no added calcium control); and (6) placebo (no added calcium or fluoride control). Human enamel slabs (36) were each cut into half-slabs and covered with one of the six dental varnishes to create a window. The half-slabs were then individually immersed in a polyacrylate demineralization buffer pH 4.8 for four days at 37 degrees C with a change of solution each day. Mineral content was determined using transverse microradiography. RESULTS: All fluoride-containing varnishes significantly inhibited enamel demineralization when compared with the placebo varnish. However, out of the calcium phosphate and fluoride containing varnishes only MI Varnish, containing fluoride and CPP-ACP was superior to the fluoride-alone varnishes. MI Varnish also released the highest levels of calcium, phosphate and fluoride ions. CONCLUSIONS: MI Varnish containing fluoride and CPP-ACP was superior to the other varnishes in protecting against enamel demineralization. PMID- 26541510 TI - Divergent subcortical activity for distinct executive functions: stopping and shifting in obsessive compulsive disorder. AB - BACKGROUND: There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined. METHOD: We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression. RESULTS: Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation. CONCLUSIONS: OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression. PMID- 26541511 TI - Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma. AB - BACKGROUND: Ipilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma. PATIENTS AND METHODS: We undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months. RESULTS: 103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %, 14 % and 27 %, respectively. Median OS was 6.8 months (95 % CI 5.3-9.9) for cutaneous, 9.6 months (95 % CI 1.6-11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %, 17 % and 11 %, respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %), none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %), including 20 grade 3-4 events (19 %). No new and unexpected safety findings were noted. CONCLUSIONS: Ipilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines. TRIAL REGISTRATION: Clinical Trials.gov NCT01355120. PMID- 26541513 TI - Cytokinin response factors regulate PIN-FORMED auxin transporters. AB - Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development. PMID- 26541515 TI - A homozygous AHI1 gene mutation (p.Thr304AsnfsX6) in a consanguineous Moroccan family with Joubert syndrome: a case report. AB - INTRODUCTION: Joubert syndrome is a rare congenital disorder characterized by brain malformation, developmental delay with hypotonia, ocular motor apraxia, and breathing abnormalities. Joubert syndrome is a genetically highly heterogeneous ciliopathy disorder with 23 identified causative genes. The diagnosis is based on brain imaging showing the "molar tooth sign" with cerebellar vermis agenesis. We describe a consanguineous Moroccan family with three affected siblings (18-year old boy, 13-year-old girl, and 10-year-old boy) showing typical signs of Joubert syndrome, and attempt to identify the underlying genetic defect in this family. METHODS: We performed genome-wide homozygosity mapping using a high-resolution array followed by targeted Sanger sequencing to identify the causative gene. RESULTS: This approach found three homozygous regions, one including the AHI1 gene. Direct sequencing of the 26 coding exons of AHI1 revealed a homozygous mutation (p.Thr304AsnfsX6) located in exon 7 present in the three Joubert syndrome-affected Moroccan siblings. Of more interest, this truncating mutation was previously reported in patients with compound heterozygous Joubert syndrome originating from Spain (one patient) and from the Netherlands (two patients), suggesting a possible founder effect or mutational hotspot. CONCLUSIONS: Combined homozygosity mapping and targeted sequencing allowed the rapid detection of the disease-causing mutation in the AHI1 gene in this family affected with a highly genetically heterogeneous disorder. Carriers of the same truncating mutation (p.Thr304AsnfsX6), originating from Spain and the Netherlands, presented variable clinical characteristics, thereby corroborating the extreme heterogeneity of Joubert syndrome. PMID- 26541514 TI - A transient ischemic environment induces reversible compaction of chromatin. AB - BACKGROUND: Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones. RESULTS: Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin. CONCLUSIONS: These studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells. PMID- 26541517 TI - Novel B(Ar')2(Ar'') hetero-tri(aryl)boranes: a systematic study of Lewis acidity. AB - A series of homo- and hetero-tri(aryl)boranes incorporating pentafluorophenyl, 3,5-bis(trifluoromethyl)phenyl, and pentachlorophenyl groups, four of which are novel species, have been studied as the acidic component of frustrated Lewis pairs for the heterolytic cleavage of H2. Under mild conditions eight of these will cleave H2; the rate of cleavage depending on both the electrophilicity of the borane and the steric bulk around the boron atom. Electrochemical studies allow comparisons of the electrophilicity with spectroscopic measurements of Lewis acidity for different series of boranes. Discrepancies in the correlation between these two types of measurements, combined with structural characterisation of each borane, reveal that the twist of the aryl rings with respect to the boron-centred trigonal plane is significant from both a steric and electronic perspective, and is an important consideration in the design of tri(aryl)boranes as Lewis acids. PMID- 26541516 TI - Cost-effectiveness of dapagliflozin versus DPP-4 inhibitors as an add-on to Metformin in the Treatment of Type 2 Diabetes Mellitus from a UK Healthcare System Perspective. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic, progressive condition where the primary treatment goal is to maintain control of glycated haemoglobin (HbA1c). In order for healthcare decision makers to ensure patients receive the highest standard of care within the available budget, the clinical benefits of each treatment option must be balanced against the economic consequences. The aim of this study was to assess the cost-effectiveness of dapagliflozin, the first-in class sodium-glucose co-transporter 2 (SGLT2) inhibitor, compared with a dipeptidyl peptidase-4 inhibitor (DPP-4i), when added to metformin for the treatment of patients with T2DM inadequately controlled on metformin alone. METHODS: The previously published and validated Cardiff diabetes model was used as the basis for this economic evaluation, with treatment effect parameters sourced from a systematic review and network meta-analysis. Costs, derived from a UK healthcare system perspective, and quality-adjusted life years (QALYs), were used to present the final outcome as an incremental cost-effectiveness ratio (ICER) over a lifetime horizon. Univariate and probabilistic sensitivity analyses (PSA) were carried out to assess uncertainty in the model results. RESULTS: Compared with DPP-4i, dapagliflozin was associated with a mean incremental benefit of 0.032 QALYs (95% confidence interval [CI]: -0.022, 0.140) and with an incremental cost of L216 (95% CI: L-258, L795). This resulted in an ICER point estimate of L6,761 per QALY gained. Sensitivity analysis determined incremental costs to be insensitive to variation in most parameters, with only the treatment effect on weight having a notable impact on the incremental QALYs; however, there were no scenarios which raised the ICER above L15,000 per QALY. The PSA estimated that dapagliflozin had an 85% probability of being cost-effective at a willingness-to-pay threshold of L20,000 per QALY gained. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option from a UK healthcare system perspective for patients with T2DM who are inadequately controlled on metformin alone. PMID- 26541518 TI - A rare case report of giant epicardial lipoma compressing the right atrium with septal enhancement. AB - BACKGROUND: Cardiac Lipoma is a rare entity constituting approximately 10-19 % of primary tumors of the heart and pericardium. To our best knowledge, such a large cardiac lipoma with septal enhancement in our case has never been reported before. CASE PRESENTATION: Here we present a rare case of a 65-year-old symptomatic female with an unusual giant cardiac lipoma. Due to the enhancement of the tumor septa, it was first diagnosed as liposarcoma and thought to be unresectable. Debulking surgery was performed to release patient's symptoms. CONCLUSIONS: The patient ultimately underwent complete tumor resection with uneventful postoperative evolution. The postoperative pathological diagnosis is cardiac lipoma. PMID- 26541519 TI - Commuting mode and pulmonary function in Shanghai, China. AB - Exposure to air pollution can be particularly high during commuting and may depend on the mode of transportation. We investigated the impact of commuting mode on pulmonary function in Shanghai, China.The Shanghai Putuo Study is a cross sectional, population-based study. Our primary outcomes were forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) % predicted, and the secondary outcome was spirometric airflow obstruction. We tested the association between mode of transportation and these outcomes after adjusting for confounders.The study population consisted of 20 102 subjects. After adjusting for confounders, the change (95% CI) in FEV1 was -2.15% pred (-2.88- -1.42% pred) among pedestrians, -1.32% pred (-2.05- -0.59% pred) among those taking buses without air conditioning, -1.33% pred (-2.05- -0.61% pred) among those taking buses with air conditioning and -2.83% pred (-5.56- -0.10% pred) among those using underground railways, as compared to cyclists (the reference group). The effects of mode on FVC % predicted were in the same direction. Private car use had a significant protective effect on FVC % predicted and the risk of airflow obstruction (defined by Global Initiative for Chronic Obstructive Lung Disease but not by lower limit of normal criteria).Mode of transportation is associated with differences in lung function, which may reflect pollution levels in different transportation microenvironments. PMID- 26541520 TI - Novel concepts in airway inflammation and remodelling in asthma. AB - The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease modifying therapeutic strategies. PMID- 26541521 TI - Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity. AB - Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, alpha1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45+/-20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41+/-31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow. PMID- 26541522 TI - Amoxicillin for clinically unsuspected pneumonia in primary care: subgroup analysis. PMID- 26541523 TI - Occupational exposure to organic solvents: a risk factor for pulmonary veno occlusive disease. AB - Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension characterised by predominant remodelling of pulmonary venules. Bi-allelic mutations in the eukaryotic translation initiation factor 2alpha kinase 4 (EIF2AK4) gene were recently described as the major cause of heritable PVOD, but risk factors associated with PVOD remain poorly understood. Occupational exposures have been proposed as a potential risk factor for PVOD, but epidemiological studies are lacking.A case-control study was conducted in consecutive PVOD (cases, n=33) and pulmonary arterial hypertension patients (controls, n=65). Occupational exposure was evaluated via questionnaire interview with blinded assessments using an expert consensus approach and a job exposure matrix (JEM).Using the expert consensus approach, PVOD was significantly associated with occupational exposure to organic solvents (adjusted OR 12.8, 95% CI 2.7-60.8), with trichloroethylene being the main agent implicated (adjusted OR 8.2, 95% CI 1.4-49.4). JEM analysis independently confirmed the association between PVOD and trichloroethylene exposure. Absence of significant trichloroethylene exposure was associated with a younger age of disease (54.8+/ 21.4 years, p=0.037) and a high prevalence of harbouring bi-allelic EIF2AK4 mutations (41.7% versus 0%, p=0.015).Occupational exposure to organic solvents may represent a novel risk factor for PVOD. Genetic background and environmental exposure appear to influence the phenotypic expression of the disease. PMID- 26541524 TI - NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD. AB - Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage. PMID- 26541525 TI - Lung cancer survival in Norway, 1997-2011: from nihilism to optimism. AB - We examine changes in survival and patient-, tumour- and treatment-related factors among resected and nonresected lung cancer patients, and identify subgroups with the largest and smallest survival improvements.National population based data from the Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register were linked for lung cancer patients diagnosed during 1997-2011. The 1- and 5-year relative survival were estimated, and Cox proportional hazard regression, adjusted for selected patient characteristics, was used to assess prognostic factors for survival in lung cancer patients overall and stratified by resection status.We identified 34 157 patients with lung cancer. The proportion of histological diagnoses accompanied by molecular genetics testing increased from 0% to 26%, while those accompanied by immunohistochemistry increased from 8% to 26%. The 1-year relative survival among nonresected and resected patients increased from 21.7% to 34.2% and 75.4% to 91.5%, respectively. The improved survival remained significant after adjustment for age, sex, stage and histology. The largest improvements in survival occurred among resected and adenocarcinoma patients, while patients >=80 years experienced the smallest increase.Lung cancer survival has increased considerably in Norway. The explanation is probably multifactorial, including improved attitude towards diagnostic work-up and treatment, and more accurate diagnostic testing that allows for improved selection for resection and improved treatment options. PMID- 26541526 TI - Prenatal maternal psychological stress and childhood asthma and wheezing: a meta analysis. AB - The aim of this study was to systematically review and meta-analyse observational studies on prenatal maternal psychological stress and the subsequent development of asthma and wheezing in early childhood.All available published literature from 1960 until November 2013 was systematically searched through electronic databases (PubMed, Embase, PsycInfo and Web of Science). All observational studies assessing associations between any form of prenatal maternal psychological stress and respiratory morbidity in the child were included. Data extraction, quality assessment and meta-analyses were performed.The overall meta-analysis included 10 studies and showed that the prevalence of wheezing, asthma and other respiratory symptoms is higher in children of mothers who were exposed to or experienced some form of psychological stress during pregnancy than in mothers who did not (pooled OR 1.56 (95% CI 1.36-1.80)). Comparable results were observed in subgroup analyses of stress exposure, perceived stress, asthma and wheezing.This study demonstrates that prenatal maternal psychological stress is associated with respiratory morbidity, including asthma and wheezing in the child. Future studies examining the early origins of asthma and wheezing need to account for the impact of prenatal maternal stress. PMID- 26541528 TI - Detection of pepsin in sputum: a rapid and objective measure of airways reflux. PMID- 26541527 TI - Interleukin-15 is associated with disease severity in viral bronchiolitis. AB - Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis. PMID- 26541529 TI - Sequential multimodality bronchoscopic investigation of peripheral pulmonary lesions. AB - Multiple guidance modalities may be combined during bronchoscopic investigation of peripheral pulmonary lesions (PPLs). The relative contribution of each modality to diagnostic performance remains uncertain.Endobronchial ultrasound (EBUS) with virtual bronchoscopy (VB) was routinely performed, with electromagnetic navigation (EMN) utilised only where EBUS was unable to locate PPLs or where the probe was adjacent to the lesion and on-site cytologic examination was nondiagnostic.236 consecutive patients with 245 PPLs had lesion size 22.8+/-12.4 mm (mean+/-sd). PPLs were localised using EBUS+VB alone in 188 (77%) and was diagnostic in 134 of these (71.3%). EBUS localisation was predicted by PPL size (23.7+/-10.5 versus 19.7+/-9.8 mm, p=0.003), but not by bronchus sign, PPL-hilum distance or PPL-pleura distance. EMN in 57 patients achieved EBUS localisation in a further 17 patients (30.9%), improving overall visualisation yield to 85%. Nine of these 57 procedures achieved a definitive diagnosis (16%), improving overall diagnostic yield to 58.4%. Probe position and lesion type influenced overall diagnostic yield. Sensitivity for diagnosis of lung cancer was 70% (131/188; 95% CI 63-76%).Localisation rate and diagnostic sensitivity of radial probe EBUS+VB alone for diagnosis of PPLs is high. EBUS localisation rates and procedural yield are improved only modestly (by 8% and 4%, respectively) with addition of EMN. Sampling following EMN should include all available methods to maximise diagnostic yield. PMID- 26541530 TI - Hypertensive disorders of pregnancy, respiratory outcomes and atopy in childhood. AB - Few epidemiological studies have investigated the role of hypertensive disorders of pregnancy in the aetiology of childhood respiratory and atopic outcomes.In the Avon Longitudinal Study of Parents and Children we examined associations of maternal gestational hypertension, hypertension before pregnancy and pre eclampsia with wheezing at 18 months, wheezing and asthma at 7 years and lung function at 8-9 years, after controlling for potential confounders (n=5322-8734, depending on outcome).Gestational hypertension was not associated with any of the outcomes. There was weak evidence for a positive association between pre eclampsia and early wheezing (adjusted OR 1.31, 95% CI 0.94-1.82, compared to normotensive pregnancies) and for negative associations between pre-eclampsia and forced expiratory volume in 1 s (adjusted mean difference in sd score -0.14, 95% CI -0.33-0.06) and maximal mid-expiratory flow (-0.15, 95% CI -0.34-0.04). Hypertension before pregnancy was positively associated with wheezing (OR 1.63, 95% CI 1.16-2.31) and asthma (OR 1.34, 95% CI 1.00-1.79).Gestational hypertension is unlikely to be a risk factor for childhood respiratory disorders; hypertension before pregnancy may be a risk factor for childhood wheezing and asthma, but this finding needs replication. Larger studies are needed to confirm whether pre eclampsia is associated with impaired childhood lung function. PMID- 26541531 TI - Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure. AB - Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension. PMID- 26541532 TI - Sex-specific features of emphysema among current and former smokers with COPD. AB - Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25% emphysema).Compared with females, males had higher log %LAA: overall (1.97+/-1.4 versus 1.69+/-1.6, beta=0.32 (0.04), p=1.34*10(-14)), and among non-Hispanic white (p=8.37*10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p<0.001).This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction. PMID- 26541533 TI - Obstructive sleep apnoea in the general population: highly prevalent but minimal symptoms. AB - The aim was to assess the prevalence of obstructive sleep apnoea (OSA) as defined by an apnoea-hypopnea index (AHI) >=15 in the middle-aged general population, and the interrelationship between OSA, sleep-related symptoms, sleepiness and vigilance.A general population sample of 40-65-year-old Icelanders was invited to participate in a study protocol that included a type 3 sleep study, questionnaire and a psychomotor vigilance test (PVT).Among the 415 subjects included in the study, 56.9% had no OSA (AHI <5), 24.1% had mild OSA (AHI 5-14.9), 12.5% had moderate OSA (AHI 15-29.9), 2.9% had severe OSA (AHI >=30) and 3.6% were already diagnosed and receiving OSA treatment. However, no significant relationship was found between AHI and subjective sleepiness or clinical symptoms. A relationship with objective vigilance assessed by PVT was only found for those with AHI >=30. Subjects already on OSA treatment and those accepting OSA treatment after participating in the study were more symptomatic and sleepier than others with similar OSA severity, as assessed by the AHI.In a middle-aged general population, approximately one in five subjects had moderate-to-severe OSA, but the majority of them were neither symptomatic nor sleepy and did not have impaired vigilance. PMID- 26541534 TI - Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer. AB - The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8(+) TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3(+) TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8(+) islet (HR 0.48, p<0.001) and Foxp3(+) stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3(+) and CD8(+) stromal counts and high Foxp3(+) islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8(+) TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3(+) TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC. PMID- 26541535 TI - Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management. AB - This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes.h(-1), those with an AHI of 1-5 episodes.h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7). PMID- 26541536 TI - Tuberculosis elimination, patients' lives and rational use of new drugs: revisited. PMID- 26541537 TI - Bacteraemia in outpatients with community-acquired pneumonia. PMID- 26541538 TI - Clinical features of large cell neuroendocrine carcinoma: a population-based overview. AB - Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11 844), SqCC (n=19 633) and AdC (n=24 253) cases were selected from the Netherlands Cancer Registry (2003 2012). Patient characteristics, metastasis at diagnosis (2006 or later), overall survival (OS) including multivariate Cox models and first-line treatment were compared for stage I-II, III and IV disease.The number of LCNEC cases increased from 56 patients in 2003 to 143 in 2012, accounting for 0.9% of all lung cancers. Stage IV LCNEC patients (n=383) commonly had metastasis in the liver (47%), bone (32%) and brain (23%), resembling SCLC. Median OS (95% CI) of stage I-II, III and IV LCNEC patients was 32.4 (22.0-42.9), 12.6 (10.3-15.0) and 4.0 (3.5-4.6) months, respectively. Multivariate-adjusted OS of LCNEC patients resembled that of SCLC patients, and was poorer than those of SqCC and AdC patients. However, frequency of surgical resection and adjuvant chemotherapy resembled SqCC and AdC more than SCLC.Diagnosis of LCNEC has increased in recent years. The metastatic pattern of LCNEC resembles SCLC as does the OS. However, early-stage treatment strategies seem more comparable to those of SqCC and AdC. PMID- 26541539 TI - Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. AB - There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis.Using the Clinical Practice Research Datalink for participants registered between January 1, 2004 and December 31, 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time.The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2 per 100 000 person-years in 2004 to 35.2 per 100 000 person-years in 2013 and in men from 18.2 per 100 000 person years in 2004 to 26.9 per 100 000 person-years in 2013. The point prevalence in women increased from 350.5 per 100 000 in 2004 to 566.1 per 100 000 in 2013 and in men from 301.2 per 100 000 in 2004 to 485.5 per 100 000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11 862) with mortality rates in the general population from Office of National Statistics data showed that in women the age-adjusted mortality rate for the bronchiectasis population was 1437.7 per 100 000 and for the general population 635.9 per 100 000 (comparative mortality figure of 2.26). In men, the age adjusted mortality rate for the bronchiectasis population was 1914.6 per 100 000 and for the general population 895.2 per 100 000 (comparative mortality figure of 2.14).Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality. PMID- 26541540 TI - Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma. AB - Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed.We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome.Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and survival. SQCC patients with keratinisation, small cell nest size, high stromal content and extensive budding had shorter overall survival. A combined grading scheme composed of the two most reliable validated prognostic markers, i.e. budding and nest size, resulted in an age-, stage- and sex-independent prognosticator for overall survival with a hazard ratio of 1.6 for grade 2 tumours and a hazard ratio of 3.7 for grade 3 tumours when compared with grade 1 neoplasms (p<0.001).Morphological characteristics of SQCC have significant prognostic impact and could constitute the basis for a diagnostically relevant future SQCC grading scheme. PMID- 26541546 TI - A qualitative study examining the presence and consequences of moral framings in patients' and mental health workers' experiences of community treatment orders. AB - BACKGROUND: Mental health recovery involves acknowledging the importance of building the person's capacity for agency. This might be particularly important for patients on community treatment orders (CTOs - which involve enforced treatment for their mental illness), given limited international evidence for their effectiveness and underlying concerns about the use of coercion by workers and systems of care towards this population of people with mental illness. METHODS: This study sought to understand how the meaning of CTOs is constructed and experienced, from the perspective of patients on CTOs and workers directly administering CTOs. Qualitative interviews were conducted with South Australian community mental health patients (n = 8) and mental health workers (n = 10) in 2013-14. During thematic analysis of data, assisted by NVIVO software, the researchers were struck by the language used by both groups of participants and so undertook an examination of the moral framings apparent within the data. RESULTS: Moral framing was apparent in participants' constructions and evaluations of the CTO experience as positive, negative or justifiable. Most patient participants appeared to use moral framing to: try to understand why they were placed on a CTO; make sense of the experience of being on a CTO; and convey the lessons they have learnt. Worker participants appeared to use moral framing to justify the imposition of care. Empathy was part of this, as was patients' positive right to services and treatment, which they believed would only occur for these patients via a CTO. Workers positioned themselves as trying to put themselves in the patients' shoes as a way of acting virtuously towards them, softening the coercive stick approach. Four themes were identified: explicit moral framing; best interests of the patient; lessons learned by the patient; and, empathy. CONCLUSIONS: Experiences of CTOs are multi-layered, and depend critically upon empathy and reflection on the relationship between what is done and how it is done. This includes explicit examination of the moral framing present in everyday interactions between mental health workers and their patients in order to overcome the paradox of the moral grey zone between caring and controlling. It suggests a need for workers to receive ongoing empathy training. PMID- 26541547 TI - Construction of a high-density genetic map and mapping of a sex-linked locus for the brown alga Undaria pinnatifida (Phaeophyceae) based on large scale marker development by specific length amplified fragment (SLAF) sequencing. AB - BACKGROUND: Undaria pinnatifida is an important economic brown alga in East Asian countries. However, its genetic and genomic information is very scarce, which hinders further research in this species. A high-density genetic map is a basic tool for fundamental and applied research such as discovery of functional genes and mapping of quantitative trait loci (QTL). In this study the recently developed specific length amplified fragment sequencing (SLAF-seq) technology was employed to construct a high-density genetic linkage map and locate a sex determining locus for U. pinnatifida. RESULTS: A total of 28.06 Gb data including 140.31 M pair-end reads was obtained. After linkage analysis 4626 SLAF markers were mapped onto the genetic map. After adding the sex linked simple sequence repeat (SSR) marker [GenBank:AY738602.1], the final genetic map was 1816.28 cM long, consisting of 30 linkage groups with an average distance of 0.39 cM between adjacent markers. The length of LGs ranged from 20.12 to 106.95 cM. A major sex associated QTL was mapped to LG22 within a window starting at 29.01 cM and ending at 68.81 cM with a total of 68 SLAF markers. The SSR marker and five SLAF markers (Marker6556, 19020, 43089, 60771 and 26359) were identified as tightly sex-linked markers, as indicated by the absence of recombination between them and the sex phenotype. These markers were located at the position of 59.50 cM, which was supposed to be the sex determining region. CONCLUSIONS: A high-density genetic linkage map was constructed using SLAF-seq technique and F1 gametophyte population for the first time in the economically important brown alga U. pinnatifida. For the first time, a major sex associated QTL suggesting a sex determining region was mapped to a single LG. This map will facilitate the further fundamental and applied research such as QTL mapping and map-based gene clone in U. pinnatifida and provide a reference for studies in other kelp species. PMID- 26541548 TI - Readout-segmented echo-planar imaging in the evaluation of sinonasal lesions: A comprehensive comparison of image quality in single-shot echo-planar imaging. AB - PURPOSE: To investigate the role of readout-segmented echo-planar imaging using parallel imaging and a two-dimensional (2D) navigator (RESOLVE) in the evaluation of sinonasal lesions and to qualitatively and quantitatively compare the image qualities of single-shot echo-planar imaging (SS-EPI) and RESOLVE. MATERIALS AND METHODS: Both sinonasal SS-EPI and RESOLVE images were acquired from 32 patients on a 3-T MR scanner. Image quality, lesion conspicuity and the distortions of the SS-EPI and RESOLVE images were qualitatively evaluated by two radiologists. Distortion was also quantitatively evaluated by comparing the distances between the same anatomic points on TSE-T1WI, TSE-T2WI, SS-EPI and RESOLVE images. The apparent diffusion coefficient (ADC) values, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the two DWIs were compared. RESULTS: The comparisons of the qualitative scores indicated that RESOLVE significantly improved the image quality and lesion conspicuity and reduced the distortion of the sinonasal diseases. The orbit, skull base, temporal bone and upper neck were also better displayed on RESOLVE. Quantitative evaluations revealed that RESOLVE greatly reduced but did not completely remove the distortion. The ADC values of the sinonasal lesions on RESOLVE were lower than those on SS-EPI, whereas no differences were found in the brainstem. The SNR of RESOLVE was lower than that of SS-EPI. There were no differences in the CNRs of the two diffusion-weighted imaging (DWI) techniques. CONCLUSION: RESOLVE significantly improved the image quality for evaluations of sinonasal lesions by reducing the susceptibility artifacts, distortion and blurring compared with SS-EPI. RESOVLE offers more accurate ADC values of sinonasal lesions than SS-EPI. PMID- 26541549 TI - Spectrum adequacy of antibiotic regimens for secondary peritonitis: a retrospective analysis in intermediate and intensive care unit patients. AB - BACKGROUND: Secondary peritonitis requires surgical source control and adequate antimicrobial treatment. Antimicrobial regimens are usually selected according to local susceptibility data of individual pathogens against single agents, but this neglects both the polymicrobial nature of the infection and the use of combination therapy. We analysed the probability of common regimens to cover all relevant pathogens isolated in one patient ("spectrum adequacy rate", SAR) in a real-life data set. METHODS: Data from 242 patients with secondary peritonitis (88 community acquired, 154 postoperative cases) treated in our IMCU/ICU were obtained retrospectively. The relative frequency of pathogens, resistance rates and the SAR were analysed using the free software R. RESULTS: Enterococci were isolated in 47.1 % of all patients, followed by Escherichia coli (42.6 %), other enterobacteriaceae (33.1 %), anaerobes (29.8 %) and Candida spp. (28.9 %). Resistance patterns were consistent with general surveillance data from our hospital. The susceptibility rates and SAR were lower in postoperative than in community acquired cases. The following regimens yielded a SAR > 95 % when enterobacteriaceae only were considered: piperacillin/tazobactam + gentamicin, cefotaxim (only for community acquired cases), cefotaxim + gentamicin, meropenem, tigecycline + gentamicin or tigecycline + ciprofloxaxin. When enterococci were also considered, all betalactam based regimens required combination with vancomycin or linezolid for a SAR > 95 %, whereas TGC based regimens were not compromised. As for Candida spp., the SAR of fluconazole was 81.9-87.5 %. CONCLUSIONS: This study demonstrates a rational approach to assess the adequacy of antimicrobial regimens in secondary peritonitis, which may help to adjust local guidelines or to select candidate regimens for clinical studies. PMID- 26541550 TI - Illness perceptions and coping in physical health conditions: A meta-analysis. AB - OBJECTIVE: There is a considerable body of research linking elements of Leventhal's Common Sense Model (CSM) to emotional well-being/distress outcomes among people with physical illness. The present study aims to consolidate this literature and examine the evidence for the role of coping strategies within this literature. METHODS: A systematic review was conducted where the outcomes of interest were: depression, anxiety and quality of life. A total of 1050 articles were identified and 31 articles were considered eligible to be included in the review. RESULTS: Across a range of illnesses, perceptions of consequences of the illness and emotional representations were consistently the illness perceptions with the strongest relationship with the outcomes. Coping variables tend to be stronger predictors of outcomes than the illness perception variables. The evidence for the mediating effect of coping was inconsistent. CONCLUSIONS: Illness perceptions and coping have an important role to play in the explanation of distress outcomes across a range of physical health conditions. However, some clarity about the theoretical position of coping in relation to illness perceptions, and further longitudinal work is needed if we are to apply this information to the design of interventions for the improvement of psychological health among people with physical health conditions. PMID- 26541551 TI - Photo-excitation intensity dependent electron and hole injections from lead iodide perovskite to nanocrystalline TiO2 and spiro-OMeTAD. AB - Photo-excitation intensity dependent electron and hole injections from CH3NH3PbI3 perovskite to nanocrystalline TiO2 and spiro-OMeTAD are presented with the electron injection yield decrease from 95% to 10% and the hole injection yield decrease from 99% to 50% by increasing the excitation intensity from 10 nJ cm(-2) to 50 MUJ cm(-2). PMID- 26541552 TI - Mercury (Hg) exposure and its effects on Saudi breastfed infant's neurodevelopment. AB - This cross-sectional study analyzed mercury (Hg) levels in healthy Saudi mothers and their infants (age 3-12 months) and examined the influence of Hg on the infants' neurodevelopment using screening tools, such as the Denver Developmental Screening Test II (DDST-II) and Parents' Evaluation of Developmental Status (PEDS). A total of 944 mothers and their 944 infants were recruited from 57 Primary Health Care Centers (PHCCs) in Riyadh. The total Hg (THg) levels were measured in the mothers' and infants' urine (UTHg-M and UTHg-I) and hair (HTHg-M and HTHg-I) samples and in the breast milk and mothers' blood. Methylmercury (MeHg) levels were determined in hair samples from the mothers (MeHg-M) and infants (MeHg-I). Only 40.1% of the infants were breast-fed when enrolled, and 59.9% had stopped breastfeeding. Only 1.8% of the mothers and 0.3% of the infants had MeHg levels above the Environmental Proection Agency (EPA) reference dose (1 MUg/g), with low medians of 0.132 and 0.091 MUg/g dw, respectively, but the MeHg levels were significantly associated with infant DDST-II performance. The levels of corrected UTHg-M for creatinine (Cr), HTHg-M, HTHg-I, and HMeHg-M, however, displayed an association with infant PEDS performance. The medians and percentage of the tested population that exceeded the recommended limits for Hg in urine and hair set by the World Health Organization (5 MUg/g Cr) and EPA (1 MUg/g) were 0.695 MUg/g Cr and 3% UTHg, 0.118 MUg/g dw and 4.1% HTHg-M, 0.101 MUg/g dw and 2.8% HTHg-I, and 0.132 MUg/g dw and 1.8% HMeHg-M. Our study provides evidence of an association between some Hg measures and delays in infant neurodevelopment, despite their low levels and regardless of the infant's breastfeeding status. The results are of potential concern, because delayed psychomotor or mental performance in infants could be an indicator of later neurocognitive development in children, which may persist into adulthood, as shown in other studies. The absence of local standardization of the DDST-II and PEDS screening tools might raise some questions, although the DDST-II has been used in local institutions for a number of years. The development of effective standardized developmental screening tools is necessary to ensure that all children at risk of neurodevelopmental problems early in life are identified so that they can receive appropriate and timely intervention. PMID- 26541553 TI - Effective characterization of polymer residues on two-dimensional materials by Raman spectroscopy. AB - Large-area two-dimensional (2D) materials grown by chemical vapor deposition need to be transferred onto a target substrate for real applications. Poly(methyl methacrylate) as a supporting layer is widely used during the transfer process and removed after finishing it. However, it is a challenge to diminish the polymer layer completely. It is necessary to readily characterize the polymer residues on 2D materials to facilitate the removal process. Here, we report a method that characterizes the polymer residues on 2D materials by tracking the presence of G-band of amorphous carbons (a-Cs) in the Raman spectrum after forming carbonized a-Cs through thermal annealing. The (13)C-graphene is employed to separate the Raman signal G-band between (12)C-a-Cs and (13)C-graphene in the Raman spectrum. The residence of the polymer residues is clearly confirmed by the different Raman signals of two different isotopes ((12)C and (13)C) due to differences in mass. Our effective method recognizes that while the polymer residue is not easily removed on graphene, those on hexagonal boron nitride and molybdenum disulfide are almost diminished under optimum thermal annealing conditions. Our method will not only contribute to the development of a new transfer process, but also help to achieve a clean surface of 2D materials. PMID- 26541554 TI - [Attacks on health professionals]. PMID- 26541555 TI - [Attitudes to insomnia by Primary Care physicians of Majorca (Spain)]. AB - OBJECTIVES: To describe the current clinical management of insomnia by family physicians. DESIGN: Cross-sectional study. SETTING: Majorca Health Area, 2011 2012. PARTICIPANTS: Family physicians (FP). Paediatricians, resident physicians and emergency physicians were excluded. MEASUREMENTS: Using a self-administered questionnaire, the following variables were collected: social, demographic, professional, training in insomnia, prescription preferences, and its clinical management. RESULTS: A total of 322 of 435 physicians answered (74%), of whom 55% were female. The mean age was 48 years with a mean of 21 years in the profession. Most of them consider insomnia as a major health problem, and refer to asking patients about sleep habits and its impact on daily life. About one third have been trained in insomnia in the last 5 years. Very few (0.6%) refers patients to a psychiatrist, and 1.9% to a psychologist. The most prescribed drugs are benzodiazepines (33.4%) and Z drugs (25.7%), with 69.4% of them claiming to have checked the treatment after month of onset. Most refer to advice about sleep hygiene measures (85.1%), 15.1% prescribe herbal remedies, and 14.2% behavioural cognitive therapy (CBT). Seven out of ten physicians consider CBT as effective and applicable by both physicians and nurses. The older FPs prescribe benzodiazepines with less frequency, while female FPs prescribe more sleep hygiene measures and herbal remedies. CONCLUSIONS: Most FPs consider insomnia as a major health problem, in which they usually get involved. The most commonly used treatments are sleep hygiene advice, followed by benzodiazepines and Z drugs. The CBT is considered effective but not widely used. PMID- 26541556 TI - The cross-sectional and longitudinal relationships between white matter hyperintensities and dementia in patients with Parkinson's disease: A retrospective analysis of 132 patients in a single center. AB - OBJECTIVE: To clarify the cross-sectional and longitudinal relationships between white matter hyperintensities (WMH) and dementia in Parkinson's disease (PD) patients. METHODS: One hundred thirty-two PD patients were included. Using medical records, the patient data including Hoehn and Yahr stage, postural instability, neuropsychological tests and magnetic resonance imaging were analyzed. The degree of WMH was rated according to a modified Fazekas scale. The relationship between the variables and dementia was analyzed using the independent t-test, the chi-square test, logistic regression analysis and the Cox proportional hazard model. RESULTS: The mean age of the study patients (35 males and 97 females) was 71.6 years (range, 45-93 years). The baseline WMH was associated not only cross-sectionally with the contemporary prevalence of dementia but also longitudinally with subsequent occurrence of dementia in the univariate analysis. These relationships became attenuated and statistically insignificant in the multivariate analysis after adjusting for confounders. It was postural instability that consistently predicted dementia in both the cross sectional and the longitudinal data. CONCLUSIONS: Our study showed that baseline WMH was not independently associated with dementia, and instead postural instability revealed at first examination can be a more reliable predictor of dementia in PD patients. PMID- 26541557 TI - The Camberwell Assessment of Need for the Elderly questionnaire as a tool for the assessment of needs in elderly individuals living in long-term care institutions. AB - OBJECTIVES: The aim of the study was to evaluate the Camberwell Assessment of Need for the Elderly questionnaire (CANE) in assessing the needs of elderly individuals living in long-term care institutions (LTCI) in Poland. SETTING AND PARTICIPANTS: The needs of 173 residents were assessed. The inclusion criteria were age (at least 75 years of age) and the lack of severe cognitive impairment (Mini Mental Scale Examination score of at least 15 points). MEASUREMENTS: In all participants, met and unmet needs were assessed by themselves and by the nursing staff involved in care activities. RESULTS: The number of met needs assessed by the staff was higher than in the users' opinions (p<0.0001), whereas the number of unmet needs was lower (p<0.001). However, the average percentage of the agreement between the user and the staff was as high as 86.2%. The areas characterized by the lowest agreement were Company (65.3%), Memory (75.7%), Eyesight/hearing/communication (70.5%) and Psychological distress (70.5%). CONCLUSIONS: Despite a high percentage of agreement reached between the staff and user assessments of needs in our study, we were able to identify the areas of discrepancies between these two perceptions of needs. These can be treated as signals pointing to those aspects of care that should be addressed. PMID- 26541558 TI - Metacognition moderates the relationship of disturbances in attachment with severity of borderline personality disorder among persons in treatment of substance use disorders. AB - OBJECTIVES: Borderline personality disorder traits have been observed to be linked with both insecure attachment styles as well as deficits in mentalizing and metacognition. Less is known, however, about how attachment style does or does not interact with deficits in mentalizing and metacognition to create, sustain, or influence levels of borderline personality disorder traits. In this study, we examined the hypothesis that metacognitive mastery, which is the ability to use knowledge about mental states of self and others to cope with distress and solve social problems, moderates the relationship of anxious attachment style with the severity of borderline personality disorder traits. METHODS: Concurrent assessments were gathered of metacognitive mastery using the Metacognitive Assessment Scale Abbreviated, anxious attachment style using the Experiences of in Close Relationships Scale, and borderline personality disorder traits using the Structured Clinical Interview for DSM-IV Axis II Disorders. Participants were 59 adults in an early phase of recovery from substance use disorders in a residential setting. RESULTS: Multiple regression revealed that metacognitive mastery moderated the relationship of anxious attachment style with the number of borderline personality disorder traits. A median split of the anxious attachment and metacognitive mastery scores was performed yielding 4 groups. An analysis of covariance revealed that participants with higher levels of anxious attachment and poorer metacognitive mastery had more borderline personality disorder traits did than the other groups after controlling for levels of psychopathology. CONCLUSION: Insecure attachment may be associated with higher number of borderline personality disorder traits in the presence of deficits in metacognitive mastery. Patients with substance use and borderline personality disorder traits may benefit from treatment which addresses metacognitive mastery. PMID- 26541559 TI - Resilience in the Offspring of Depressed Mothers: Variation Across Risk, Domains, and Time. AB - Considerable research has demonstrated that maternal depression is a significant risk factor for emotional and behavioral problems in children and adolescents (Goodman and Gotlib in Psychol Rev 106:458-490, 1999). It is important to note, however, that most children of depressed parents do not develop problems. This review will examine studies of resilience as they relate to the degree to which positive adjustment occurs across different levels of risk (i.e., severity and chronicity of depression as well as in context of multiple risk factors), domains of adjustment, and time. Understanding the phenomenon of resilience to depression is of critical importance to prevention and intervention experts because it may provide insight into processes that can be enhanced and targeted in prevention approaches among high-risk populations. PMID- 26541560 TI - The Application of Intensive Longitudinal Methods to Investigate Change: Stimulating the Field of Applied Family Research. AB - The use of intensive longitudinal methods (ILM)-rapid in situ assessment at micro timescales-can be overlaid on RCTs and other study designs in applied family research. Particularly, when done as part of a multiple timescale design-in bursts over macro timescales-ILM can advance the study of the mechanisms and effects of family interventions and processes of family change. ILM confers measurement benefits in accurately assessing momentary and variable experiences and captures fine-grained dynamic pictures of time-ordered processes. Thus, ILM allows opportunities to investigate new research questions about intervention effects on within-subject (i.e., within-person, within-family) variability (i.e., dynamic constructs) and about the time-ordered change process that interventions induce in families and family members beginning with the first intervention session. This paper discusses the need and rationale for applying ILM to family intervention evaluation, new research questions that can be addressed with ILM, example research using ILM in the related fields of basic family research and the evaluation of individual-based interventions. Finally, the paper touches on practical challenges and considerations associated with ILM and points readers to resources for the application of ILM. PMID- 26541561 TI - [Shoulder dystocia: Guidelines for clinical practice--Short text]. AB - OBJECTIVES: To determine the available evidence to prevent and treat shoulder dystocia to attempt to decrease its related neonatal and maternal morbidity. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: Shoulder dystocia, defined as a vaginal delivery that requires additional obstetric maneuvers to deliver the fetus after the head has delivered and gentle traction has failed, complicates 0.5-1 % of vaginal deliveries. Risks of brachial plexus birth injury (LE3), clavicle and humeral fracture (LE3), perinatal asphyxia (LE2), hypoxic-ischemic encephalopathy (LE3) and perinatal mortality (LE2) are increased after shoulder dystocia. Its main risk factors are previous shoulder dystocia and macrosomia, but they are poorly predictive; 50 % to 70 % of shoulder dystocia cases occur in their absence, and the great majority of deliveries when they are present are not associated with shoulder dystocia. No study has proven that the correction of these risk factors (except gestational diabetes) would reduce the risk of shoulder dystocia (SD). Physical activity is recommended before and during pregnancy to reduce the occurrence of some risk factors for shoulder dystocia (grade C). In obese patients, physical activity should be coupled with dietary measures to reduce fetal macrosomia and weight gain during pregnancy (grade A). In case of gestational diabetes, diabetes care is recommended (diabetic diet, glucose monitoring, insulin if needed) (grade A) as it reduces the risk of macrosomia and shoulder dystocia (LE1). In order to avoid shoulder dystocia and its complications, only two measures are proposed. Induction of labor is recommended in case of impending macrosomia if the cervix is favourable and gestational age greater than 39 weeks of gestation (professional consensus). Cesarean delivery is recommended before labor in case of EFW greater than 4500g if associated with maternal diabetes (grade C), EFW greater than 5000g in the absence of maternal diabetes (grade C), history of shoulder dystocia associated with severe neonatal or maternal complications (Professional consensus), and finally during labor, in case of fetal macrosomia and failure to progress in the second stage, when the fetal head is above a +2 station (grade C). In case of shoulder dystocia, it is recommended not to pull excessively on the fetal head (grade C), do not perform uterine expression (grade C) and do not realize inverse rotation of the fetal head (professional consensus). McRoberts' maneuver, with or without a suprapubic pressure, is recommended in the first line (grade C). In case of failure, if the posterior shoulder is engaged, Wood's maneuver should be performed preferentially; if the posterior shoulder is not engaged, delivery of the posterior arm should be performed preferentially (professional consensus). It seems necessary to know at least two maneuvers to perform in case of shoulder dystocia unresolved by the maneuver of McRoberts (professional consensus). Pediatrician should be immediately informed in case of shoulder dystocia. The initial clinical examination should search complications such as brachial plexus birth injury or clavicle fracture (professional consensus). In absence of neonatal complication, monitoring of the neonate is not modified (professional consensus). The implementation of a practical training using simulation and concerning all caregivers of the delivery room is associated with a significant reduction in neonatal (LE3) but not maternal (LE3) injury. CONCLUSION: Shoulder dystocia remains a non-predictable obstetrics emergency. All physicians and midwives should know and perform obstetric maneuvers if needed quickly but without precipitation. A training program using simulation for the management of shoulder dystocia is encouraged for the initial and continuing formation of different actors in the delivery room (professional consensus). PMID- 26541562 TI - [Exploring a non-inflammatory clinical breast mass: Clinical practice guidelines]. AB - PURPOSE: The aim of the study was to assess the diagnostic value of physical examination, radiologic explorations and percutaneous procedures of the breast in the exploration of a non-inflammatory palpable mass, in order to propose guidelines. METHOD: A systematic literature review was conducted in the Medline and Cochrane library databases. International guidelines in French and English language were also consulted until April 30th 2015. RESULTS: Physical examination of a non-inflammatory palpable breast mass is not sufficient to eliminate a breast cancer (LE2). Mammography alone has a sensitivity between 70 and 95% for the diagnosis of breast cancer (LE3). Echography alone has a sensitivity of 98 to 100% for the diagnosis of breast cancer (LE2). The core needle biopsy has a better sensitivity and specificity than the fine-needle aspiration for breast cancer diagnosis (LE2). The association of mammography and 2D echography presents excellent sensitivity and negative predictive value (close to 100 %) to exclude a breast cancer (LE3). A double evaluation using mammography and echography is recommended in the exploration of a non-inflammatory palpable breast mass (grade B). PMID- 26541563 TI - [Inflammatory and infectious breast mastitis outside of pregnancy and lactation: Guidelines]. AB - OBJECTIVES: This work's objective was to define the various non-cancerous inflammatory and infectious mastitis, which may occur outside of pregnancy and lactation, and to identify recommendations for their care based on an exhaustive literature review. MATERIALS AND METHODS: A literature review was conducted by consulting Medline, Cochrane Library, Google scholar and international recommendations in French and English until 31st August 2014. RESULTS AND CONCLUSION: Infectious mastitis (periareolar abscess) is the most common form of non-puerperal abscesses and it is recommended that a suction/drainage needle for abscesses under 5 cm, involving antibiotic therapy (grade C). For abscesses over 5 cm, there is no evidence to recommend a first surgery or suction/drainage. Inflammatory mastitis can be primary or secondary to a systemic disease (diabetes, collagen...; LE4). In case of idiopathic granulomatous mastitis, a steroid therapy or surgery may be indicated, without one or the other of these methods can be recommended. In case of plasma cell mastitis or ductal ectasia, no treatment is recommended. PMID- 26541564 TI - [Breast imaging of mass, architectural distortion and asymmetry: Clinical practice guidelines]. AB - The development of the mammary imaging (mammography, ultrasound, MRI) enables the discovery of more and more lesions. The BI-RADS lexicon is the reference book for their descriptive analysis. Four elementary images must be individualized: masses and architectural distortion described in 3 imaging techniques, asymmetries and microcalcifications described in mammography. The aim of this work was to review three of these images: mass, architectural distortion and asymmetry, allowing the various actors involved in senology to propose an up-to-date diagnostic and interventional strategy, based on their positive predictive values (PPV) or negative predictive values of cancer and allowing the classification BI-RADS of the lesion. The masses are the most often encountered lesions as well in screening as in diagnosis. Their PPV is superior in diagnosis than in screening and it increases with the age. Their irregular forms, their spiculated outlines and their evolutionary character are the most relevant elements of suspicion. The architectural distortion is the rarest image and always classified suspect BI RADS 4, except in case of a known scar. The asymmetry is less common; its PPV is low and rises only in case of evolutionary asymmetry. PMID- 26541566 TI - [Guidelines for clinical practice: Post-partum--Introduction]. PMID- 26541565 TI - [Benign breast tumors: Recommendations of College National des Gynecologues Obstetriciens Francais (CNGOF)--Short text]. AB - Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C). PMID- 26541567 TI - [Breast pain: Recommendations]. AB - OBJECTIVES: To evaluate the diagnostic value of clinical examination and additional tests in the exploration of breast pain, to evaluate the strategy of their care and to provide recommendations. METHODS: A literature search in English and French carried out by consulting the databases PubMed, Cochrane Library and international recommendations. RESULTS: Clinical examination and interrogation, with the use of visual analog scale used to differentiate non cyclical breast pain from mastodynia (LE2). A calendar can be used to characterize the cyclical breast pain (LE3). Using a questionnaire can help to characterize the pain (LE3). In the absence of palpable abnormality, it is not recommended to modify systematic or individual screening modalities (LE2). MRI is not recommended in case of normal mammography and sonography. Explorations biopsy is guided by imaging. The therapeutic management includes reassurance after a normal clinical evaluation and/or normal radiological findings (LE2), and precise fitting of a brassiere. In case of failure of this first approach, NSAIDs gel can be proposed (LE1-2). PMID- 26541568 TI - Iron Metabolism and Vascular Remodeling: Novel Insights Provided by Transferrin-1 Receptor Depletion in Mice With Pulmonary Hypertension. PMID- 26541569 TI - Aortic Pulse Pressure Amplification Imputed From Simple Clinical Measures Adds to the Ability of Brachial Pressure to Predict Survival. AB - BACKGROUND: Although aortic-to-brachial pulse pressure amplification (PPamp) may offer prognostic information beyond brachial blood pressure (BP), this approach is limited in resource-limited settings. We aimed to derive an equation to impute central aortic PP (PPc) from simple clinical measures and assess whether imputed PPamp adds to the ability of brachial BP to predict mortality. METHODS: An imputation equation for PPc, incorporating brachial PP, age, mean arterial pressure, and pulse rate, was identified from multivariate modeling of the factors associated with radial applanation tonometry-derived (measured) PPc in 1,179 community participants and validated in a clinical sample of 351 patients. We applied the equation to ambulatory awake BP and pulse rate values in a separate group of 4,796 patients referred for ambulatory monitoring and evaluated the impact on all-cause mortality. RESULTS: Imputed PPc values closely approximated measured PPc (r (2) = 0.96, mean difference +/- (2 * SD) = 1.4+/ 6.2mm Hg). In adjusted Cox proportional models including adjustments for awake brachial PP during 47,111 person-years of follow-up, where 648 patients died, hazards ratio for all-cause mortality per SD of awake PPamp was 0.79 (95% confidence interval (CI): 0.68-0.93, P < 0.005). The hazards ratio for brachial PP with (1.49, CI = 1.36-1.64, P < 0.0001) or without (1.46, CI = 1.35-1.59, P < 0.0001) PPamp in the model was similar. Awake PPamp also predicted survival independent of awake brachial systolic BP (P < 0.0001). CONCLUSIONS: PPc imputed from simple clinical assessments closely approximates measured PPc. PPamp derived from imputed PPc adds to the ability of brachial BP to predict survival. In resource-limited settings, an imputation equation may be employed to approximate aortic BP and enhance risk prediction. PMID- 26541570 TI - Functional Status and Antihypertensive Therapy in Older Adults: A New Perspective on Old Data. AB - BACKGROUND: Functional status may be useful for identifying older adults who benefit from lower blood pressure. We examined whether functional status modifies the effect of antihypertensive treatment among older adults. METHODS: Post hoc analyses of the Systolic Hypertension in the Elderly Program (SHEP), a randomized trial of antihypertensive therapy vs. placebo (1985-1991) in 4,736 adults aged 60 years or older with isolated systolic hypertension. Outcomes were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, falls, and symptoms of hypotension. The effect modifier of interest was functional status, assessed by self-reported physical ability limitation (PAL). RESULTS: Among persons with no PAL, those receiving treatment had a lower rate of death, CV death, and MI compared with placebo (4.0, 2.9, and 4.2 per 1,000 person-years lower, respectively). In contrast, among persons with a PAL, those receiving treatment had a higher rate of death, CV death, and MI compared with placebo (8.6, 5.3, and 2.7 per 1,000 person-years higher, respectively). These patterns persisted in Cox models, although interaction terms did not reach statistical significance. Treatment remained protective for stroke regardless of functional status. The rate of falls associated with treatment differed by functional status; incidence-rate ratio = 0.81, 95% confidence interval (CI) = (0.66, 0.99), and 1.32, 95% CI = (0.87, 2.00) in participants without and with a PAL, respectively, in models adjusted for demographics and baseline blood pressure (P value for interaction, 0.04). CONCLUSIONS: Functional status may modify the effect of antihypertensive treatment on MI, mortality, and falls, but not stroke, in older adults. Functional status should be examined in other trial settings. PMID- 26541571 TI - An updated ciguatoxin extraction method and silica cleanup for use with HPLC MS/MS for the analysis of P-CTX-1, PCTX-2 and P-CTX-3. AB - Ciguatera fish poisoning is a debilitating human neuro-intoxication caused by consumption of tropical marine organisms, contaminated with bioaccumulated ciguatoxins (CTXs). The growing number of cases coupled with the high toxicity of CTXs makes their reliable detection and quantification of paramount importance. Three commonly occurring ciguatoxins, P-CTX-1, 2 and 3 from five different ciguatoxic Spanish mackerel (Scomberomorus commerson), were used to assess the effectiveness of different extraction techniques: homogenization (high powered blending vs. ultrasonication); C-18 column sizes (500 mg vs. 900 mg); and a novel HILIC SPE cleanup. Despite minor differences, blending and sonication proved equally effective. Larger 900 mg columns offered a greater extraction efficiency, increasing detected P-CTX-1 by 37% (P < 0.001). The newly adapted cleanup was highly effective at reducing co-eluting phospholipids thereby reducing matrix effects and increasing detectable CTXs by HPLC-MS/MS. Silica cleanup extraction efficiencies were also compared between the highly effective and validated ciguatoxin rapid extraction method (CREM) and current best practice extraction method employed by Queensland Health (QH). Overall, the QH protocol proved more effective, especially when paired with the newly adapted cleanup, as this increased the amount of extracted P-CTX-1 by 46% (P < 0.01), P-CTX-2 by 10% and P CTX-3 by 71% (P = 0.001). This study suggests the QH protocol utilizing a 900 mg C-18 column and newly adapted HILIC SPE cleanup was most effective at extracting P-CTX-1, -2, -3. Specifically P-CTX-1, the primary ciguatoxin congener of concern due to its extremely high potency and an ability to cause CFP at 0.1 MUg/kg following consumption of carnivorous fish flesh. Despite being more time intensive (an additional 85 min per batch of 12 samples), this will be especially effective for assessing lower toxin burdens, which may be near the limit of detection. PMID- 26541572 TI - A bright future for integrative venomics. PMID- 26541573 TI - First report of the toxigenic Nitzschia navis-varingica (Bacillariophyceae) isolated from Tebrau Straits, Johor, Malaysia. AB - Screening of the occurrence of potentially toxic diatoms was carried out at two sites of cage cultures in Tebrau Straits, Johor. Phytoplankton samples from Sungai Pendas and Teluk Sengat were collected using a 20 MUm mesh plankton net and salinity was recorded in-situ. Nitzschia and Pseudo-nitzschia cells were isolated and established into clonal cultures. All cultures were tested for domoic acid using HPLC-UV analysis and verified by LC-MS analysis. Three Nitzschia spp. and one Pseudo-nitzschia sp. were identified from these locations. Toxic and non-toxic strains of Nitzschia navis-varingica are found at the cage culture areas. Cellular toxin content in the toxic strain of N. navis-varingica is 1.8 pg cell(-1). This is a new record from Malaysia and this species was isolated from estuarine water with salinity 28 PSU. The discovery of toxic Nitzschia species in Tebrau Straits indicates the potential for domoic acid accumulation in seafood. PMID- 26541574 TI - Modulation of jellyfish nematocyst discharges and management of human skin stings in Nemopilema nomurai and Carybdea mora. AB - Even though jellyfish sting is common today, its first aid guideline has never been clear enough in a scientific point of view and the use of vinegar appears to be not accepted in common throughout the world. In the present study, to develop rational first aid guidelines for the stings of Nemopilema nomurai (scyphozoa) and Carybdea mora (cubozoa), the modulatory effects of various kinds of rinsing solutions have been assessed on nematocyst discharge and human skin tests. Among the solutions tested, vinegar (4% acetic acid) immediately caused significant nematocyst discharge in N. nomurai but not in C. mora. On the other hand, ethanol (70%) notably stimulated nematocyst discharge in C. mora and relatively less in N. nomurai. Moreover, isopropanol, a widely used solvent in pharmaceutical products, caused extensive nematocyst discharges in both N. nomurai and C. mora. Whereas, seawater did not elicit any nematocyst discharge in both jellyfish species. In human skin test, the rinsing with seawater also ameliorated the stinging-associated symptoms (pain and redness) in C. mora as well as N. nomurai. From this study, seawater appears not to induce any nematocyst discharge and can be safely used as a first aid rinsing solution for the jellyfish stings. PMID- 26541575 TI - Practitioner perspectives. PMID- 26541576 TI - News from the International Council on Women's Health Issues. PMID- 26541577 TI - Removal of a bent intramedullary nail in lower extremity: report of two cases and review of removal techniques. AB - Removal of a bent intramedullary nail (IMN) is a rare but challenging orthopedic problem. Several removal techniques have been described up to date; however, there is no extensive review and no algorithm to manage these cases in current literature. The purpose of this paper is to present two cases that presented with bent IMN and provide an algorithm for management of this rare complication. PMID- 26541578 TI - Design of a fluorescent ligand targeting the S-adenosylmethionine binding site of the histone methyltransferase MLL1. AB - The histone methyltransferase MLL1 has been linked to translocation-associated gene fusion in childhood leukemias and is an attractive drug target. High throughput biochemical analysis of MLL1 methyltransferase activity requires the production of at least a trimeric complex of MLL1, RbBP5 and WDR5 to elicit robust activity. Production of trimeric and higher order MLL1 complexes in the quantities and reproducibility required for high-throughput screening presents a significant impediment to MLL1 drug discovery efforts. We present here a small molecule fluorescent ligand (FL-NAH, 6) that is able to bind to the S adenosylmethionine (SAM) binding site of MLL1 in a manner independent of the associated complex members. We have used FL-NAH to develop a fluorescence polarization-based SAM displacement assay in a 384-well format targeting the MLL1 SET domain in the absence of associated complex members. FL-NAH competes with SAM and is displaced from the MLL1 SET domain by other SAM-binding site ligands with Kdisp values similar to the higher-order complexes, but is unaffected by the H3 peptide substrate. This assay enables screening for SAM-competitive MLL1 inhibitors without requiring the use of trimeric or higher order MLL1 complexes, significantly reducing screening time and cost. PMID- 26541579 TI - Validation of Duruoz Hand Index in patients with tetraplegia. AB - STUDY DESIGN: Cross-sectional, clinical measurement. PURPOSE: To investigate the validity of the Duruoz Hand Index (DHI) in the assessment of hand function in patients with tetraplegia. METHODS: A total of 40 patients with tetraplegia participated. Patients' upper extremities were assessed on the level of 'body function and structure' [The American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS) 2000 revised criteria, upper extremity motor score (UEMS), neurologic level of injury and visual analogue scale of hand function (VAS-HF)], 'activity' [DHI and Quadriplegia index of function-short form (QIF-SF)] and 'body function and structure, activity and participation' [Health Survey Short Form-36 (SF-36)] according to International Classification of Function. RESULTS: The DHI showed significant correlations with UEMS, AIS, QIF-SF, VAS-HF, physical functioning and physical compound summary scores of SF-36. CONCLUSIONS: The DHI was found a valid method in the assessment of hand functions in patients with tetraplegia. LEVEL OF EVIDENCE: Diagnostic III. PMID- 26541580 TI - Neural correlates of successful memory retrieval in aging: Do executive functioning and task difficulty matter? AB - The current experiment aimed to explore age differences in brain activity associated with successful memory retrieval in older adults with different levels of executive functioning, at different levels of task demand. Memory performance and fMRI activity during a recognition task were compared between a young group and two older groups characterized by a low (old-low group) vs. high (old-high group) level of executive functioning. Participants first encoded pictures, presented once (Hard condition) or twice (Easy condition), and then completed a recognition memory task. Old-low adults had poorer memory performance than the two other groups, which did not differ, in both levels of task demands. In the Easy condition, even though older adults demonstrated reduced activity compared to young adults in several regions, they also showed additional activations in the right superior frontal gyrus and right parietal lobule (positively correlated to memory accuracy) for the old-high group and in the right precuneus (negatively correlated to memory accuracy), right anterior cingulate gyrus and right supramarginal gyrus for the old-low group. In the Hard condition, some regions were also more activated in the young group than in the older groups. Vice versa, old-high participants demonstrated more activity than either the young or the old low group in the right frontal gyrus, associated with more accurate memory performance, and in the left frontal gyrus. In sum, the present study clearly showed that age differences in the neural correlates of retrieval success were modulated by task difficulty, as suggested by the CRUNCH model, but also by interindividual variability, in particular regarding executive functioning. PMID- 26541582 TI - Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway. AB - BACKGROUND: Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect. METHODS: Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3beta, p-GSK-3beta by Western bolting and mPTP opening. RESULTS: Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3beta. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it. CONCLUSIONS: Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3beta pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury. PMID- 26541581 TI - Auditory short-term memory in the primate auditory cortex. AB - Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active 'working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a 'match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory. PMID- 26541583 TI - Dexamethazone protects against Escherichia coli induced sickness behavior in rats. AB - Systemic bacterial infection results in systemic inflammatory response syndrome due to the release of lipopolysaccharide (LPS) in blood that can lead to multiple organ failure, shock, and potentially death. Other impact, LPS exposure produces robust increase in anxiety-like behavior, suppression of locomotor, exploratory activity, and reduced social behavior. The therapeutic use of glucocorticoids in septic shock remains one of the first-aid approaches for their anti-inflammatory properties. The aim of this study was to evaluate the possible protective effect of dexamethazone (DEX), the most commonly used corticosteroid, against Escherichia coli (E. coli) immunohistochemical changes and neurobehavioral dysfunction. To this end, male Sprague-Dawley rats were divided into four groups; (1) Control group (2) E. coli infected group, where animals received 0.2 ml of 24 h growth of E. coli suspension in nutrient broth containing approximately 1.8*10(8) cfu/ml i.p for once, 48 h before sacrificing (3) DEX (20 mg/kg, i.p, 3 days) treated group (4) DEX and E. coli treated group. The results revealed that DEX significantly protected animals against most E. coli-induced behavioral deficits, reduced signs of cognitive impairment. DEX also reduced the LPS-evoked rise in C-reactive protein (CRP), Interferon gamma (IFgamma), as well as, expression of Caspase-3. In conclusion, DEX provides neuroprotection against E. coli-associated neurobehavioral and immunological changes via its anti inflammatory and immunomodulatory effects. PMID- 26541584 TI - Growth and lipid content at low temperature of Arctic alga Chlamydomonas sp. KNM0029C. AB - Biodiesel produced from microalgae is a promising source of alternative energy. In winter, however, outdoor mass cultivation for biodiesel production is hampered by poor growth. Here, we report that Arctic Chlamydomonas sp. KNM0029C exhibits optimal growth at 4 degrees C and reaches densities up to 1.4 * 10(7) cells mL( 1). Lipid body formation in the alga was visualized through BODIPY 505/515 staining and fluorescence microscopy. The fatty acid methyl ester (FAME) production level of KNM0029C was 178.6 mg L(-1) culture and 2.3-fold higher than that of C. reinhardtii CC-125 at 4 degrees C. Analysis of the FAME content showed a predominance of polyunsaturated fatty acids such as C16:3, C18:2, C18:3, and C20:2. C18:3 fatty acids comprised the largest fraction (20.7%), and the content of polyunsaturated fatty acids (39.6%) was higher than that of saturated fatty acids (6.8%) at 4 degrees C. These results indicate that Chlamydomonas sp. KNM0029C, as a psychrophilic microalga, might represent a favorable source for biodiesel production in cold environments. PMID- 26541585 TI - Cost evaluation of cellulase enzyme for industrial-scale cellulosic ethanol production based on rigorous Aspen Plus modeling. AB - Cost reduction on cellulase enzyme usage has been the central effort in the commercialization of fuel ethanol production from lignocellulose biomass. Therefore, establishing an accurate evaluation method on cellulase enzyme cost is crucially important to support the health development of the future biorefinery industry. Currently, the cellulase cost evaluation methods were complicated and various controversial or even conflict results were presented. To give a reliable evaluation on this important topic, a rigorous analysis based on the Aspen Plus flowsheet simulation in the commercial scale ethanol plant was proposed in this study. The minimum ethanol selling price (MESP) was used as the indicator to show the impacts of varying enzyme supply modes, enzyme prices, process parameters, as well as enzyme loading on the enzyme cost. The results reveal that the enzyme cost drives the cellulosic ethanol price below the minimum profit point when the enzyme is purchased from the current industrial enzyme market. An innovative production of cellulase enzyme such as on-site enzyme production should be explored and tested in the industrial scale to yield an economically sound enzyme supply for the future cellulosic ethanol production. PMID- 26541586 TI - Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma. AB - Patients with metastatic, platinum-resistant urothelial carcinoma (PRUC) have no Food and Drug Administration-approved therapies. The response rates to second line chemotherapy have generally been < 20%, with a median overall survival of < 1 year. We report our experience with 6 heavily pretreated patients with advanced PRUC (ClinicalTrials.gov identifier NCT01631552) with the novel antibody-drug conjugate, sacituzumab govitecan (IMMU-132). This antibody-drug conjugate comprises the active metabolite of irinotecan, SN-38, conjugated to an anti-Trop 2 antibody. Trop-2 is widely expressed in <= 83% of urothelial carcinomas. Of the 6 patients, 3 had a clinically significant response (progression-free survival, 6.7 to 8.2 months; overall survival, 7.5+ to 11.4+ months). Sacituzumab govitecan was well tolerated. Because of these results, a phase II trial has been initiated. The present report highlights the promise of antibody-drug conjugates, such as sacituzumab govitecan, as a novel therapeutic strategy for the treatment of PRUC. PMID- 26541587 TI - Modification of cellular DNA by synthetic aziridinomitosenes. AB - Two synthetic aziridinomitosenes (AZMs), Me-AZM and H-AZM, structurally related to mitomycin C (MC) were evaluated for their anticancer activity against six cancer cell lines (HeLa, Jurkat, T47D, HepG2, HL-60, and HuT-78) and tested for their DNA-modifying abilities in Jurkat cells. Cytotoxicity assays showed that Me AZM is up to 72-fold and 520-fold more potent than MC and H-AZM, respectively. Me AZM also demonstrated increased DNA modification over MC and H-AZM in alkaline COMET and Hoechst fluorescence assays that measured crosslinks in cellular DNA. Me-AZM and H-AZM treatment of Jurkat cells was found to sponsor significant DNA protein crosslinks using a K-SDS assay. The results clearly indicate that the AZM C6/C7 substitution pattern plays an important role in drug activity and supports both DNA-DNA and DNA-protein adduct formation as mechanisms for inducing cytotoxic effects. PMID- 26541588 TI - Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells. AB - Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site. PMID- 26541589 TI - [The "obese" and "old" male patient in dermatological practice. When should hypogonadism be considered?]. AB - Hypogonadism refers to reduced endocrine function of the testicles and leads to testosterone deficiency. It is often observed in older and obese men. Symptoms with the highest predictive value are reduced sexual thoughts, decreased spontaneous erections, and erectile dysfunction. After excluding contraindications (e.g., desire for children), various forms of replacement therapy are available. Studies have shown that testosterone therapy is safe if regularly checked. PMID- 26541590 TI - Mopping up miRNA: An integrated HBV transcript disrupts liver homeostasis by sequestering miR-122. PMID- 26541591 TI - Movin' on Up: Socioeconomic Mobility and the Risk of Delivering a Small-for Gestational Age Infant. AB - OBJECTIVE: Poor fetal growth is associated with increased rates of adverse health outcomes in children and adults. The social determinants of poor fetal growth are not well understood. Using multiple socioeconomic indicators measured at the individual level, this study examined changes in maternal socioeconomic position (SEP) from childhood to adulthood (socioeconomic mobility) in relation to poor fetal growth in offspring. METHODS: Data were from the Pregnancy Outcomes and Community Health Study (September 1998-June 2004) that enrolled women in mid pregnancy from 52 clinics in five Michigan communities (2463 women: 1824 non Hispanic White, 639 non-Hispanic Black). Fetal growth was defined by birthweight for-gestational age percentiles; infants with birthweight-for-gestational age <10th percentile were referred to as small-for-gestational age (SGA). In logistic regression models, mothers whose SEP changed from childhood to adulthood were compared to two reference groups, the socioeconomic group they left and the group they joined. RESULTS: Approximately, 8.2 % of women (non-Hispanic White: 6.3 %, non-Hispanic Black: 13.9 %) delivered an SGA infant. Upward mobility was associated with decreased risk of delivering an SGA infant. Overall, the SGA adjusted-odds ratio was 0.34 [95 % confidence interval (CI) 0.17-0.69] for women who moved from lower to middle/upper versus static lower class, and 0.44 (CI 0.28 1.04) for women who moved from middle to upper versus static middle class. There were no significant differences in SGA risk when women were compared to the SEP group they joined. CONCLUSIONS: Our findings support a link between mother's socioeconomic mobility and SGA offspring. Policies that allow for the redistribution or reinvestment of resources may reduce disparities in rates of SGA births. PMID- 26541592 TI - Mother's Self-Efficacy Mediates the Relationship Between Household Food Insecurity and Maternal Infant Feeding Styles. AB - OBJECTIVES: This study was performed to examine the association between household food insecurity, self-efficacy and infant feeding styles in mothers with children under 2 years old in Varamin, Iran. METHODS: In this cross-sectional study, 423 mothers aged 17-40 years from different areas of Varamin were selected by a multistage sampling methods from October 2013 to February 2014. The questionnaires consisted of three valid instruments, including: Household Food Insecurity Access Scale, Comprehensive Feeding Practices Questionnaire and Mother's Self-Efficacy Questionnaire. Data were analyzed using Chi-square, t tests, ANOVA, Pearson correlations and multiple linear regressions. Structural equation modeling was also used. RESULTS: Mild and moderate-severe food insecurity was observed in 39.5 and 12.8 % of the households respectively. Mean score of mother's self-efficacy in food secure households was 32.5 +/- 3.7; while in mild food insecure and moderate-severe food insecure households were 31.9 +/- 3.1 and 28.4 +/- 4.0, respectively (P = 0.001). There was a significant negative correlation between household food insecurity and mother's self-efficacy (r = 0.297, P < 0.01). Significant correlation was seen between mother's self-efficacy and the maternal infant feeding styles. Household food insecurity and mother's self-efficacy had significant relationship with mother-infant feeding styles: control of home food access [beta (SE)] = [-0.015(0.004), P = 0.001]; restriction for weight control [beta = 0.038(0.013), P = 0.003]; restriction for health [beta = 0.019(0.008), P = 0.027] and encouragement [=0.018(0.006), P = 0.001]. The model had sufficient fitness with data of the research (CFI = 0.927, RMSEA = 0.076). CONCLUSIONS: Our findings suggest that performing interventions in order to enhance mother's self-efficacy in food insecure households can lead to improve positive maternal feeding behaviors. PMID- 26541593 TI - A Preliminary Study of New Parents, Sleep Disruption, and Driving: A Population at Risk? AB - BACKGROUND: Drowsy driving is estimated to be a causal factor in 2-16 % of vehicular crashes. Several populations are reported to be at high risk for drowsy driving accidents, including shift workers, teenage drivers, medical residents, and pilots. Although new parents are known to have significant sleep disruption, no study has investigated vehicular accidents or near miss accidents in this population. METHODS: A preliminary cross-sectional, anonymous survey of parents who had given birth within the previous 12 months. Participants were asked about their sleep, including validated measures of sleep disruption, their driving patterns, and information about near miss traffic accidents and actual crashes. RESULTS: Overall, 72 participants were enrolled. A large proportion of participants had poor sleep including approximately 30 % with daytime sleepiness, 60 % with poor daytime function and two-thirds with poor sleep quality. The mean sleep duration was only 6.4 h. Although most participants drove <100 miles per week, 22.2 % reported at least one near miss accident and 5.6 % reported a crash. Sleep problems were more common in those with near miss accidents and actual crashes than in those without. Of note, poor sleep quality was associated with a sixfold increase in near miss accidents even after accounting for other factors. CONCLUSION: Poor sleep is common in new parents and we provide preliminary evidence that sleep disruption in this population is associated with near miss motor vehicle accidents. Drowsy driving results in thousands of unnecessary serious injuries and fatalities each year; raising public awareness that new parents are a high-risk group is important. PMID- 26541594 TI - Comamonas phosphati sp. nov., isolated from a phosphate mine. AB - A Gram-stain-negative, facultatively anaerobic, non-pigmented, non-sporulating, rod-shaped bacterial strain (WYH 22-41T) was isolated from a phosphate mine in Yunnan Province, China. The cells were motile with a single polar flagellum. The 16S rRNA gene of strain WYH 22-41T was phylogenetically related to the corresponding gene of Comamonas terrae DSM 27221T (98.4 % 16S rRNA gene sequence similarity), Comamonas odontotermitis LMG 23579T (97.6 %) and Comamonas aquatica LMG 2370T (97.4 %). DNA-DNA hybridizations of strain WYH 22-41T with these three strains showed relatedness values of 33.2 %, 20.5 % and 27.7 %, respectively. The DNA G+C content of strain WYH 22-41T was 62.4 mol%. The predominant respiratory quinone was ubiquinone-8. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The major fatty acids of strain WYH 22-41T were C16 : 0, C17 : 0 cyclo, summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c). On the basis of phenotypic properties, phylogenetic characteristics, DNA-DNA hybridization, as well as whole-cell fatty acid composition, strain WYH 22-41T represents a novel species of the genus Comamonas, for which the name Comamonas phosphati sp. nov. is proposed. The type strain is WYH 22-41T ( = CGMCC 1.12294T = DSM 26017T). PMID- 26541595 TI - Airflow, transport and regional deposition of aerosol particles during chronic bronchitis of human central airways. AB - In the present study, the effects of airway blockage in chronic bronchitis disease on the flow patterns and transport/deposition of micro-particles in a human symmetric triple bifurcation lung airway model, i.e., Weibel's generations G3-G6 was investigated. A computational fluid and particle dynamics model was implemented, validated and applied in order to evaluate the airflow and particle transport/deposition in central airways. Three breathing patterns, i.e., resting, light activity and moderate exercise, were considered. Using Lagrangian approach for particle tracking and random particle injection, an unsteady particle tracking method was performed to simulate the transport and deposition of micron sized aerosol particles in human central airways. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting particles in sequentially bifurcating rigid airways, airflow patterns and particle transport/deposition in healthy and chronic bronchitis (CB) affected airways were evaluated and compared. Comparison of deposition efficiency (DE) of aerosols in healthy and occluded airways showed that at the same flow rates DE values are typically larger in occluded airways. While in healthy airways, particles deposit mainly around the carinal ridges and flow dividers--due to direct inertial impaction, in CB affected airways they deposit mainly on the tubular surfaces of blocked airways because of gravitational sedimentation. PMID- 26541596 TI - Association of genetic polymorphisms in PTEN and additional gene-gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population. AB - This study aims to investigate the association of five single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homologue (PTEN) gene and additional role of gene-gene interaction with esophageal squamous cell carcinoma (ESCC), based on a Chinese case-control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case-control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio (OR) and 95% confident interval (95%CI) were calculated. All genotypes were distributed according to Hardy-Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild-type homozygotes, and OR (95%CI) were 1.27 (1.09-2.08) and 1.45 (1.17-1.98), respectively. We also found a potential gene-gene interaction between rs2735343 and rs701848 (P = 0.0010), and a potential gene-gene interaction among all five SNP (P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37-3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene-gene interaction between rs2735343 and rs701848 and a potential gene-gene interaction among all five SNPs. PMID- 26541597 TI - Asian elephants acquire inaccessible food by blowing. AB - Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication. PMID- 26541598 TI - Anesthetic management of a pregnant patient with cerebral angioma scheduled for caesarean section. AB - Pregnancy can be rarely complicated with cerebral angioma. Such patients can pose a problem to the anesthesiologist and can present for caesarean section (CS). The main anesthetic challenge is prevention of rupture of angioma and subsequent bleed due to intraoperative surge of blood pressure. Both general anesthesia and regional anesthesia have been used in such patients. Spinal anesthesia has the advantage of safety, less hypertensive surge, and better analgesia as well as less blood loss. We hereby present successful anesthetic management of such a case presented for emergency CS done under spinal anesthesia. PMID- 26541599 TI - Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir((r)) Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies. AB - BACKGROUND AND OBJECTIVE: Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir(r) hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI. METHODS: Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 ug/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged >=12 years were randomly assigned to receive 90 or 180 MUg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2). RESULTS: Study 1: differences, with corresponding 90% confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 ug. Both study treatments were generally well tolerated. CONCLUSION: The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol. PMID- 26541600 TI - Fluid flow and particle transport in mechanically ventilated airways. Part II: particle transport. AB - The flow mechanisms that play a role on aerosol deposition were identified and presented in a companion paper (Timothy et al. in Med Biol Eng Comput. doi: 10.1007/s11517-015-1407-3 , 2015). In the current paper, the effects of invasive conventional mechanical ventilation waveforms and endotracheal tube (ETT) on the aerosol transport were investigated. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by jet caused by the ETT. The orientation of the ETT toward right bronchus resulted in a substantial deposition inside right lung compared to left lung. The deposition inside right lung was ~12-fold higher than left lung for all considered cases, except for the case of using pressure controlled sinusoidal waveform where a reduction of this ratio by ~50 % was found. The total deposition during pressure constant, volume ramp, and ascending ramp waveforms was similar and ~1.44 times higher than deposition fraction when using pressure sinusoidal waveform. Varying respiratory waveform demonstrated a significant role on the deposition enhancement factors and give evidence of drug aerosol concentrations in key deposition sites, which may be significant for drugs with negative side effects in high concentrations. These observations are thought to be important for ventilation treatment strategy. PMID- 26541601 TI - Numerical simulation of unsteady micropolar hemodynamics in a tapered catheterized artery with a combination of stenosis and aneurysm. AB - The unsteady flow characteristics of blood are analyzed through a catheterized stenotic artery with post-stenotic dilatation. A rigid tube with a pair of abnormal wall segments in close proximity to each other is employed to geometrically simulate the diseased artery. A micropolar fluid model is used to capture the rheological characteristics of the streaming blood in the annulus. The mild stenosis approximation is employed to derive the governing flow equation which is then solved using a robust finite difference method. Particular attention is paid to the effects of geometrical parameters of the arterial wall and rheological parameters of the blood on axial velocity, flow rate, resistance impedance and wall shear stress. The global behavior of blood is also analyzed through instantaneous pattern of streamlines. PMID- 26541602 TI - Effects of rs3846662 Variants on HMGCR mRNA and Protein Levels and on Markers of Alzheimer's Disease Pathology. AB - 3-Hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR) is a cholesterol regulating gene with statin relevance. rs3846662 being involved in regulation of HMGCR alternative splicing, we explored its impact on HMGCR messenger RNA (mRNA) and protein levels in the brain and the associations between those levels and levels of Alzheimer's disease pathological markers. We used brain samples derived from a cohort of 33 non-demented controls and 90 Alzheimer's disease autopsied confirmed cases. HMGCR mRNA levels were determined in the frontal cortex (n = 114) and cerebellum (n = 110) using Taqman-qPCR, and HMGCR protein levels were determined in the frontal cortex (n = 117) using a commercial enzyme immunoassay. While densities of neurofibrillary tangles and senile plaques were determined in the frontal cortex (n = 74), total tau, phosphorylated Tau, and beta-amyloid 1-42 levels were determined in the frontal cortex (n = 94) and cerebellum (n = 91) using commercial enzyme immunoassays. Despite an increase in full-length HMGCR mRNA ratio in the frontal cortex of women carrying the AA genotype, there were no associations between rs3846662 and HMGCR mRNA or protein levels. An increased Delta13 HMGCR mRNA ratio was associated with increased levels of HMGCR proteins and neurofibrillary tangles in the frontal cortex but with reduced beta-amyloid 1 42 levels in the cerebellum, suggesting a brain cell type- or a disease progression-dependent association. PMID- 26541603 TI - Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children. AB - INTRODUCTION: Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children. MATERIALS/METHODS: Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay. RESULTS: MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0.031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors. CONCLUSIONS: Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function. PMID- 26541604 TI - Obtainment and partial characterization of biodegradable gelatin films with tannic acid, bentonite and glycerol. AB - BACKGROUND: Research studies concerning the overall effect of the addition of plasticizers, cross-linking and strengthening agents in gelatin film-forming mixtures are very scarce. Also, there are no studies focused on the interactions among their individual components, or showing what sort of effects they might cause all together. A gelatin film obtained from a composite consisting of tannic acid, bentonite and glycerol was evaluated. Nine gelatin films were manufactured by the casting method, using these materials, following a 2(3) factorial design with five replicates on the central point. RESULTS: The interactions among gelatin, tannic acid and bentonite caused a decrease in hydrogen bonds, while the polar groups of the gelatin chains were less exposed to interactions with water molecules. There was an increase in temperature and enthalpy of gelatin denaturation, due to increasing tannic acid and bentonite concentration. Tactoids were found in the gelatin films, caused mainly by bentonite polydispersion. CONCLUSIONS: A synergistic effect among tannic acid, bentonite and glycerol, which overall improved the measured gelatin film properties, was found. The best film formulation was that with 40, 150 and 250 g kg(-1) gelatin of tannic acid, bentonite and glycerol respectively, displaying a tensile strength of 38 MPa, an elongation at break of 136%, water vapor permeability of 1.28 * 10(-12) g (Pa s m)(-1) and solubility of 23.4%. (c) 2015 Society of Chemical Industry. PMID- 26541605 TI - Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. AB - More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations. PMID- 26541606 TI - Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. AB - T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy. PMID- 26541607 TI - Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis. AB - The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules. PMID- 26541608 TI - Three-dimensional charge density wave order in YBa2Cu3O6.67 at high magnetic fields. AB - Charge density wave (CDW) correlations have been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from that measured with x-ray scattering at zero and low fields. We combined a pulsed magnet with an x-ray free-electron laser to characterize the CDW in YBa2Cu3O6.67 via x-ray scattering in fields of up to 28 tesla. While the zero-field CDW order, which develops at temperatures below ~150 kelvin, is essentially two dimensional, at lower temperature and beyond 15 tesla, another three-dimensionally ordered CDW emerges. The field induced CDW appears around the zero-field superconducting transition temperature; in contrast, the incommensurate in-plane ordering vector is field-independent. This implies that the two forms of CDW and high-temperature superconductivity are intimately linked. PMID- 26541609 TI - Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. AB - In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis. PMID- 26541612 TI - Induced illness in children. PMID- 26541611 TI - A General Time-Periodic Driving Approach to Realize Topological Phases in Cold Atomic Systems. AB - For time-reversal symmetric cold atomic insulating systems, it is found that the usual driving approach based on electromagnetic field used in solid state systems loses its power to drive them from trivial regimes to topological regimes if the driven systems still hold time-reversal symmetry (TRS). For such systems, we point out that simply varying the optical lattice potential periodically provides a general and effective way to drive them into topological regimes without breaking their symmetries. Based on this approach, we find that the time-reversal symmetric Kane-Mele model can be effectively driven from the trivial phase to topological phases named as Floquet Quantum Spin Hall insulator. Due to the existence of two gaps in the Floquet system, this novel state of matter can stably host one or two pair of gapless helical states on the same boundary, which suggests this state is not a simple analog of the Quantum Spin Hall insulator. This new driving approach to a system without TRS is also investigated. PMID- 26541613 TI - Pulkurlkpa: The joy of research in Aboriginal communities. PMID- 26541610 TI - Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. AB - Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade. PMID- 26541614 TI - Ben matters. PMID- 26541615 TI - The Keeper of the Label. PMID- 26541616 TI - An adolescent with recurrent cough and vomiting. PMID- 26541617 TI - Facial rash in an infant. PMID- 26541624 TI - Pocketing of food in cheeks during eating in an adolescent with CHARGE syndrome. PMID- 26541625 TI - Four-Component Relativistic DFT Calculations of (13)C Chemical Shifts of Halogenated Natural Substances. AB - We have calculated the (13)C NMR chemical shifts of a large ensemble of halogenated organic molecules (81 molecules for a total of 250 experimental (13)C NMR data at four different levels of theory), ranging from small rigid organic compounds, used to benchmark the performance of various levels of theory, to natural substances of marine origin with conformational degrees of freedom. Carbon atoms bonded to heavy halogen atoms, particularly bromine and iodine, are known to be rather challenging when it comes to the prediction of their chemical shifts by quantum methods, due to relativistic effects. In this paper, we have applied the state-of-the-art four-component relativistic density functional theory for the prediction of such NMR properties and compared the performance with two-component and nonrelativistic methods. Our results highlight the necessity to include relativistic corrections within a four-component description for the most accurate prediction of the NMR properties of halogenated organic substances. PMID- 26541627 TI - Handbook of Frontal Lobe Assessment. PMID- 26541628 TI - A Versatile Anisometric Metallic Supercrystal with Controllable Orientation on a Chip as a Stable and Reliable Label-Free Biosensor. AB - Based on anisometric noble-metal nanocrystals, a universal fabrication protocol for preparing 3D supercrystals with controlled orientation on a chip has been developed. A comparison of the surface-enhanced Raman scattering (SERS) behavior of 3D nanorod supercrystals aligned vertically and parallel to the chip indicates that the SERS-enhancing ability and reproducibility of the former is superior to the latter. The 3D nanorod supercrystals aligned vertically to the chip have been utilized as highly sensitive SERS substrates for the label-free discrimination of Gram-positive and -negative bacteria. Furthermore, to strengthen the stability of the supercrystal substrate for assays of bacteria in biosamples, a coating of the antibiotic vancomycin can dramatically increase adhesion of bacteria on a nanointerface and simultaneously improve the SERS response of bacteria to achieve a layer-by-layer assembled, stable, and reliable biosensor for bacteria. PMID- 26541631 TI - Bevacizumab for recurrent primary central nervous system lymphoma: a new treatment? PMID- 26541630 TI - Phase I study of 5-fluorouracil in children and young adults with recurrent ependymoma. AB - BACKGROUND: We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. METHODS: Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly for 4 weeks followed by a 2-week rest period, defining one cycle. Patients could continue on therapy for 16 cycles. The starting 5-FU dosage was 500 mg/m(2). Dose-limiting toxicity was determined after one cycle. Patients were initially enrolled according to a rolling-6 design; subsequent dose re-escalation phase was based on a 3 + 3 design. RESULTS: We treated patients at 400 (n = 6), 500 (n = 15), and 650 (n = 5) mg/m(2), with de-escalation due to toxicity. Twenty three of twenty-six patients enrolled were evaluable. Five patients experienced grade 4 neutropenia (n = 2: 650 mg/m(2); n = 3: 500 mg/m(2)). One patient experienced grade 3 diarrhea. At 500 mg/m(2), the median 5-FU maximal concentration, AUC0-infinity, and alpha half-life were 825 uM, 205 uM * h, and 9.9 min, respectively. Interim analysis revealed an association between hematologic toxicity and prior number of chemotherapeutic regimens (P = .03). The study was amended to re-escalate the dosage in a less heavily pretreated cohort of patients. CONCLUSIONS: These phase I clinical data provide initial pharmacokinetic parameters to describe i.v. bolus 5-FU disposition in children with recurrent ependymoma. Tumor exposures effective in preclinical testing can be achieved with tolerable bolus dosages in patients. Bolus 5-FU is well tolerated and possesses antitumor activity. PMID- 26541633 TI - Role of BGT-1 and BGT-2, two predicted GPI-anchored glycoside hydrolases/glycosyltransferases, in cell wall remodeling in Neurospora crassa. AB - Neurospora crassa BGT-1 (NCU06381) and BGT-2 (NCU09175) are two putative glycoside hydrolases (GHs) with additional predicted glycosyltransferase activity and binding sites for a glycosyl phosphatidyl inositol (GPI) anchor that would facilitate their attachment to the plasma membrane (PM). To discern their role in key morphogenetic events during vegetative development of N. crassa, BGT-1 and BGT-2 were labeled with the green fluorescent protein (GFP). The gfp was inserted immediately after the signal peptide sequence, within the bgt-1 encoding sequence, or directly before the GPI-binding site in the case of bgt-2. Both BGT 1-GFP and BGT-2-GFP were observed at the PM of the hyphal apical dome, excluding the foremost apical region and the Spitzenkorper (Spk), where chitin and beta-1,3 glucan synthases have been previously found. These and previous studies suggest a division of labor of the cell wall synthesizing machinery at the hyphal dome: at the very tip, glucans are synthesized by enzymes that accumulate at the Spk, before getting incorporated into the PM, whereas at the subtending zone below the apex, glucans are presumably hydrolyzed, producing amenable ends for further branching and crosslinking with other cell wall polymers. Additionally, BGT-1-GFP and BGT-2-GFP were observed at the leading edge of new developing septa, at unreleased interconidial junctions, at conidial poles, at germling and hyphal fusion sites, and at sites of branch emergence, all of them processes that seemingly involve cell wall remodeling. Even though single and double mutant strains for the corresponding genes did not show a drastic reduction of growth rate, bgt-2Delta and bgt-1Delta::bgt-2Delta strains exhibited an increased resistance to the cell wall stressors calcofluor white (CW) and congo red (CR) than the reference strain, which suggests they present significant architectural changes in their cell wall. Furthermore, the conidiation defects observed in the mutants indicate a significant role of BGT-1 and BGT-2 on the re-arrangement of glucans needed at the conidiophore cell wall to allow conidial separation. PMID- 26541634 TI - Prevalence and clinical characteristics of adrenal incidentalomas in potential kidney donors. AB - BACKGROUND: The prevalence of adrenal incidentalomas (AIs) in asymptomatic individuals is unknown. This study evaluated the prevalence of AIs in healthy kidney donors in whom pre-operative computed tomography (CT) is performed routinely. METHODS: All potential kidney donors evaluated at the Rabin Medical Center who had routine abdominal CT were identified and their medical records were retrospectively reviewed. Subjects who had normal CT scans were compared with those with a finding of an AI, evaluating demographic (age, body mass index, systolic and diastolic blood pressure) and laboratory variables (glucose, sodium, potassium, calcium, phosphorus, albumin and creatinine). In addition, prevalence of hypertension, rate of donation and surgical mortality were compared between the two groups. RESULTS: CT was performed in 673 potential kidney donors. Of these, 645 had a normal CT and 28 (4.2%) had evidence of an AI. Those with AIs had a similar prevalence of hypertension, kidney donation and surgical mortality as those with a normal CT. Those with AIs were older (50.93 +/- 11.1 versus 43.76 +/- 11.1 years) but other demographic variables were similar; laboratory variables were also similar except for slightly lower albumin and creatinine in those with AIs. CONCLUSIONS: The prevalence of AIs is high even in healthy asymptomatic individuals. PMID- 26541635 TI - The Essential Resilience Scale: Instrument Development and Prediction of Perceived Health and Behaviour. AB - Further advancement in stress and health research calls for better tools to assess resilience. In this study, we developed the Essential Resilience Scale (ERS) and investigated the association between ERS scores and several health and behaviour measures. We developed the ERS with an operationalized definition of resilience-an individual's capability to anticipate, be flexible with and bounce back from three types of traumatic and adverse events (physical, emotional and social). The 15-item ERS was assessed using survey data from a diverse sample (n = 238, aged 18-45 years, 76 rural-to-urban migrants, 85 rural residents, 77 urban residents) recruited in Wuhan, China. Results showed a high reliability of the ERS (alpha = 0.94). Confirmatory factor analysis demonstrated a satisfactory fit of the proposed second-order ERS measurement model (goodness-of-fit index = 0.94, comparative fit index = 0.98, root mean square error of approximation = 0.06, chi square/df = 1.75). Multivariate regression analysis indicated that ERS scores significantly predicted perceived health status, stress, anxiety, depression and cigarette smoking after controlling for important covariates. Findings of this study indicate high reliability and validity of the scale and its potential use in advancing stress and health research. Further studies are implied to provide additional support for the ERS and its relations with other health outcomes. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26541636 TI - Metallocene Catalytic Insertion Polymerization of 1-Silene to Polycarbosilanes. AB - Metallocene of zirconium were used as a catalyst for an insertion polymerization of 1-methylsilene directly into pre-ceramic precursor polyzirconocenecarbosilane (PZCS) during dechlorination of dichlorodimethylesilane by sodium, which exhibits high catalytic effectiveness with the maximum conversion ratio of polycarbosilane up to 91%. The average molecular weights of polymers synthesized are less than 1400, all with very narrow polymolecularities. The mechanism of catalytic polymerization was assumed to be similar to a coordination insertion polymerization of 1-olefins by metallocenes. The obtained PZCS show high ceramic yields with formation of composite ceramics of ZrC-SiC, which are novel polymeric precursors of ultra-high temperature ceramic (UHTC) fiber and composite. PMID- 26541637 TI - Quality assessment of gasoline using comprehensive two-dimensional gas chromatography combined with unfolded partial least squares: A reliable approach for the detection of gasoline adulteration. AB - Comprehensive two-dimensional gas chromatography and flame ionization detection combined with unfolded-partial least squares is proposed as a simple, fast and reliable method to assess the quality of gasoline and to detect its potential adulterants. The data for the calibration set are first baseline corrected using a two-dimensional asymmetric least squares algorithm. The number of significant partial least squares components to build the model is determined using the minimum value of root-mean square error of leave-one out cross validation, which was 4. In this regard, blends of gasoline with kerosene, white spirit and paint thinner as frequently used adulterants are used to make calibration samples. Appropriate statistical parameters of regression coefficient of 0.996-0.998, root mean square error of prediction of 0.005-0.010 and relative error of prediction of 1.54-3.82% for the calibration set show the reliability of the developed method. In addition, the developed method is externally validated with three samples in validation set (with a relative error of prediction below 10.0%). Finally, to test the applicability of the proposed strategy for the analysis of real samples, five real gasoline samples collected from gas stations are used for this purpose and the gasoline proportions were in range of 70-85%. Also, the relative standard deviations were below 8.5% for different samples in the prediction set. PMID- 26541639 TI - Prevalence and differential profile of patients with drug addiction problems who commit intimate partner violence. AB - BACKGROUND AND OBJECTIVES: The objectives of this study were, first, to explore the prevalence of aggressors with lifetime intimate partner violence (IPV) among patients in the Proyecto Hombre of Navarra (Spain) addiction treatment programme; and second, to know the specific and differential characteristics of patients presenting IPV as aggressors. METHODS: A sample of 162 patients (119 men and 43 women) was assessed. Data on socio-demographic and substance consumption characteristics, IPV variables, psychopathological symptoms, and personality variables were obtained. The profiles of patients in addiction treatment with and without a history of violence towards their partners were compared. RESULTS: The results showed that 33.6% of people in treatment for addiction had committed violence against their partners. This prevalence was significantly higher (chi(2) = 15.6, p < .001) in women (63.3%) than in men (24.2%). In the 98.4% of the cases the IPV was bidirectional. Patients with a history of IPV perpetration showed greater severity in substance consumption variables, psychopathological symptoms, and personality traits. Gender, the family scale on the European version of the Addiction Severity Index (EuropASI), and the aggressive-sadistic scale on the Millon Clinical Multiaxial Inventory (MCMI-III) were the main variables related to the presence of IPV as aggressors. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: There was a differential profile in patients with IPV perpetration, showing more psychopathological and personality symptoms. Moreover, in this study being a woman was one of the main predictors of committing IPV. PMID- 26541640 TI - Cardiac imaging in patients with chronic liver disease. AB - Cirrhotic cardiomyopathy (CCM) is characterized by an impaired contractile response to stress, diastolic dysfunction and the presence of electrophysiological abnormalities, and it may be diagnosed at rest in some patients or demasked by physiological or pharmacological stress. CCM seems to be involved in the development of hepatic nephropathy and is associated with an impaired survival. In the field of cardiac imaging, CCM is not yet a well characterized entity, hence various modalities of cardiac imaging have been applied. Stress testing with either physiologically or pharmacologically induced circulatory stress has been used to assess systolic dysfunction. Whereas echocardiography with tissue Doppler is by far the most preferred method to detect diastolic dysfunction with measurement of E/A- and E/E'-ratio. In addition, echocardiography may also possess the potential to evaluate systolic dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes in cirrhotic patients. PMID- 26541641 TI - Prospective control study using fibrin sealants and Harmonic(r) scalpel in Latissimus Dorsi flap transfer. AB - BACKGROUND: Latissimus dorsi flap (LD) is used in breast reconstruction procedures, although prolonged donor site drainage is a frequent complication. To decrease this problem, quilting sutures and/or fibrin sealants were proposed, with alternate results. The primary objective of this study was to assess the effectiveness of Tisseel(r) in association with the Harmonic Synergy(r) blade system to reduce this complication. MATERIALS AND METHODS: Between 2010-2012, 20 consecutive patients undergoing immediate unilateral breast reconstruction with LD were enrolled in the study (Group A) and matched with 20 patients in which LD was raised with electrocautery (Group B), and 20 patients in which LD was harvested with Harmonic(r) (Group C). After informed consent acquisition, Harmonic(r) was used in Group A for LD harvesting, but differed from other groups as fibrin glue was applied to the donor site prior to closure. In all groups donor site drainage measurements at 24 and 48 hours, total drain volume, days to drain removal, operation time, and complication rate were recorded. Pearson's Chi squared, ANOVA, and Bonferroni post-hoc tests were used to analyze the data. RESULTS: Data analysis did not show any statistical difference. Prolonged drains output >= 15 days occurred in one patient of Group A and C, and in three Group B patients. CONCLUSION: Although the combined use of Harmonic(r) and Tisseel(r) presents a low donor site fluid collection rate, the fibrin glue seems not to have further beneficial effects in reducing the post-operative serous drainage or to lead to an early drain removal when compared to Harmonic(r) only. PMID- 26541642 TI - Assessment of language impairment in bilingual children using semantic tasks: two languages classify better than one. AB - BACKGROUND: Significant progress has been made in the identification of language impairment in children are bilingual. Bilingual children's vocabulary knowledge may be distributed across languages. Thus, when testing bilingual children it is difficult to know how to weigh each language for diagnostic purposes. Even when conceptual scoring is used in vocabulary testing, bilingual children may score below that of their typical monolingual peers. AIMS: The primary aim was to evaluate the classification accuracy of two approaches (total semantics score and two-dimensional bilingual coordinate score) that combined lexical-semantic knowledge across two languages. We investigated the classification accuracy of the English and Spanish semantics subtest using the experimental version of the Bilingual English Spanish Assessment (BESA) with bilingual children with and without language impairment. METHODS: A total of 78 bilinguals with balanced exposure to English and Spanish (15 with language impairment, 63 with typical development) participated. Children were between 4;0 and 6;11 years old. Discriminant function analysis explored the extent to which these children were accurately classified when combining Spanish and English subtests. OUTCOMES & RESULTS: Discriminant analysis yielded above 85% correct classification for balanced bilingual children for both approaches. CONCLUSIONS & IMPLICATIONS: For the most accurate assessment and diagnostic decision-making for bilinguals, approaches that consider both languages together are recommended. PMID- 26541643 TI - Risk of gastric cancer, gastrointestinal cancers and other cancers: a comparison of treatment with pantoprazole and other proton pump inhibitors. AB - BACKGROUND: Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies. AIM: As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained exposures to pantoprazole, a long acting PPI, compared with other shorter acting PPIs. METHODS: We conducted a cohort study within the membership of the Kaiser Permanente Northern California healthcare system and compared rates of gastric and other cancers among pantoprazole users and users of other PPI medications. The Cox proportional hazards model was used to adjust for potential confounders such as sex, age, receipt of treatment for Helicobacter pylori, cumulative PPI dose, total years PPI treatment and year of index date. The study was developed in consultation with, and approved by, the FDA. RESULTS: A total of 61 684 persons with at least a 240-day supply of medication (34 178 pantoprazole and 27 686 other PPIs) were followed up for a total of 547 020 person-years (274 700 vs. 272 321 person years, respectively). The primary analyses demonstrated comparable risks between the pantoprazole and other PPI groups for gastric cancer [hazard ratio (HR) = 0.68, 95% CI 0.24-1.93); colorectal, liver, pancreatic, or small bowel cancers (HR = 0.95, 95% CI 0.65-1.40) or any cancer (HR = 1.06, 95% CI 0.93-1.21). CONCLUSIONS: We found no evidence that pantoprazole, a longer acting PPI, compared with shorter-acting agents, conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers for pantoprazole compared with other shorter-acting PPIs. PMID- 26541644 TI - Rapid identification of haloarchaea and methanoarchaea using the matrix assisted laser desorption/ionization time-of-flight mass spectrometry. AB - The aim of this study was to classify certain environmental haloarchaea and methanoarchaea using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to expand the archaeal mass spectral database. A total of 69 archaea were collected including type strains and samples isolated locally from different environments. For extraction of the haloarchaeal total cell peptides/proteins, a simple method of acetonitrile extraction was developed. Cluster analysis conducted with the MALDI-TOF MS data overcame the high divergence in intragenomic 16S rRNA sequences in haloarchaea and clearly distinguished Methanohalophilus mahii from M. portucalensis. Putative biomarkers that can distinguish several particular archaeal genera were also assigned. In conclusion, this study expands the mass spectral database of peptide/protein fingerprints from bacteria and fungi to the archaea domain and provides a rapid identification platform for environmental archaeal samples. PMID- 26541645 TI - Synthesis of Zn-In-S Quantum Dots with Tunable Composition and Optical Properties. AB - II-III-VI semiconductors are of interest due to their chemical stability and composition-tunable optical properties. Here, we report a methodology for the synthesis of monodisperse zinc-indium-sulfide (ZIS) alloy quantum dots (QDs, mean diameter from ~2 to 3.5 nm) with an In content substantially below that of the stoichiometric ZnIn2 S4 compound. The effects of indium incorporation on the size, lattice constant, and optical properties of ZIS QDs are elucidated. In contrast to previous reports, we employ sulfur dissolved in oleic acid as the sulfur donor rather than thioacetamide (TAA). The size of the ZIS QDs and their crystal lattice constant increased with increasing In incorporation, but they maintained the cubic sphalerite phase of ZnS, rather than the hexagonal phase typical of ZnIn2 S4 . The QDs' absorbance onset at UV wavelengths red-shifts with increasing In content and the accompanying increase in NC size. The ZIS NCs and related materials, whose synthesis is enabled by the approach presented here, provide new opportunities to apply II-III-VI semiconductors in solution-processed UV optoelectronics. PMID- 26541646 TI - Intimate partner violence perpetrated by young adult women against men in Ukraine: Examining individual, familial, and cultural factors. AB - We examined the role of financial strain, parent-to-parent violence, parent-to child violence, emotional distress, and alcohol use in intimate partner violence perpetrated by young adult women against men in Ukraine. The moderating role of acceptability of intimate partner violence and violence-related laws and regulations was also examined. Four hundred and six full-time female university students from four universities in Ukraine participated in the study. We found that emotional distress, parent-to-parent, and parent-to-child violence mediated the link between financial strain and intimate partner violence perpetrated by women on men. However, we found limited support for the moderating role of acceptability of intimate partner violence and violence-related laws and regulations in the relationship between individual and familial factors on intimate partner violence. The findings from this investigation suggest that there is a distinct need for supporting families and individuals in dealing with issues of intimate partner violence directed by women against men in Ukraine. Aggr. Behav. 42:380-393, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26541647 TI - Low-income fathers' speech to toddlers during book reading versus toy play. AB - Fathers' child-directed speech across two contexts was examined. Father-child dyads from sixty-nine low-income families were videotaped interacting during book reading and toy play when children were 2;0. Fathers used more diverse vocabulary and asked more questions during book reading while their mean length of utterance was longer during toy play. Variation in these specific characteristics of fathers' speech that differed across contexts was also positively associated with child vocabulary skill measured on the MacArthur-Bates Communicative Development Inventory. Results are discussed in terms of how different contexts elicit specific qualities of child-directed speech that may promote language use and development. PMID- 26541649 TI - Management of tacrolimus-associated food allergy after liver transplantation. AB - Increasingly, food allergy associated with tacrolimus after pediatric living donor liver transplantation (LT) has been reported. Tacrolimus prevents the activation of T cells by blocking calcineurin, thus producing an immunosuppressive effect, but tacrolimus induces an imbalance in T-helper type 1 (Th1) and Th2 cells in the food allergy process. This report describes a case of tacrolimus-associated food allergy after pediatric living-donor LT. The patient was a 7-year-old Japanese girl who had undergone living-donor LT at 12 months of age, and whom we first saw in the clinic at age 18 months. She received immunosuppressive therapy by tacrolimus after transplantation. Atopic dermatitis developed in post-transplant month 18. Stridor, facial edema, lip swelling, and skin erythema after consuming tempura udon containing wheat occurred in post transplant month 39, and she was subsequently diagnosed with anaphylactic shock. Eosinophilic leukocyte and serum immunoglobulin (Ig)E increased, and specific IgE was positive for some food allergens. Pharmacotherapy was therefore changed from tacrolimus to cyclosporine A, after which eosinophilic leukocyte and serum IgE decreased and atopic dermatitis improved. PMID- 26541648 TI - Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery. AB - The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs' mechanisms of action. A mutant of the artemisinin resistance candidate gene - "K13-propeller" gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways. PMID- 26541650 TI - Laboratory measurements of resistivity in warm dense plasmas relevant to the microphysics of brown dwarfs. AB - Since the observation of the first brown dwarf in 1995, numerous studies have led to a better understanding of the structures of these objects. Here we present a method for studying material resistivity in warm dense plasmas in the laboratory, which we relate to the microphysics of brown dwarfs through viscosity and electron collisions. Here we use X-ray polarimetry to determine the resistivity of a sulphur-doped plastic target heated to Brown Dwarf conditions by an ultra intense laser. The resistivity is determined by matching the plasma physics model to the atomic physics calculations of the measured large, positive, polarization. The inferred resistivity is larger than predicted using standard resistivity models, suggesting that these commonly used models will not adequately describe the resistivity of warm dense plasma related to the viscosity of brown dwarfs. PMID- 26541652 TI - Fluorometric sensing of ultralow As(III) concentrations using Ag doped hollow CdS/ZnS bi-layer nanoparticles. AB - Arsenic poisoning from drinking water has been an important global issue in recent years. Because of the high level toxicity of arsenic to human health, an easy, inexpensive, low level and highly selective detection technique is of great importance to take any early precautions. This study reports the synthesis of Ag doped hollow CdS/ZnS bi-layer (Ag-h-CdS/ZnS) nanoparticles for the easy fluorometric determination of As(iii) ions in the aqueous phase. The hollow bi layer structures were synthesized by a sacrificial core method using AgBr as the sacrificial core and the core was removed by dissolution in an ammonium hydroxide solution. The synthesized nanoparticles were characterized using different instrumental techniques. A good linear relationship was obtained between fluorescence quenching intensity and As(iii) concentration in the range of 0.75 22.5 MUg L(-1) at neutral pH with a limit of detection as low as 0.226 MUg L(-1). PMID- 26541651 TI - Targeting protein arginine methyltransferase 5 inhibits human hepatocellular carcinoma growth via the downregulation of beta-catenin. AB - BACKGROUND: Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in some tumors, but its role in hepatocellular carcinoma (HCC) is still unknown. METHODS: PRMT5 level in HCC specimens was determined by immunohistochemical staining and the association with clinicopathologic features was evaluated. PRMT5 was inhibited by AMI-1 (a small molecule inhibitor of PRMTs) or small interference RNA (siRNA). The proliferation of HCC cells was tested by Cell Counting Kit-8, cell migration was evaluated by Transwell assay and cell cycle and apoptosis were analyzed by flow cytometry. The effect of AMI-1 on HCC in vivo was examined by mouse xenograft model. RESULTS: PRMT5 expression was markedly upregulated in HCC tissues, and correlated inversely with overall patient survival. Knockdown of PRMT5 significantly reduced the proliferation of HCC cells, but did not affect the growth of normal liver cells. Furthermore, beta catenin was identified as a target of PRMT5. Silencing PRMT5 significantly down regulated the expression of beta-catenin and the downstream effector Cyclin D1 in HCC cells. AMI-1 strongly inhibited HCC growth in vivo, increased the ratio of Bax/Bcl-2, and led to apoptosis and loss of migratory activity in several HCC cells. Meanwhile, AMI-1 decreased the expression levels of symmetric dimethylation of H4 (H4R3me2s), a histone mark of PRMT5. CONCLUSIONS: PRMT5 plays an important role in HCC. PRMT5 may be a promising target for HCC therapy. PMID- 26541653 TI - PPIs: between overuse and underprescription when really necessary. AB - Hydrochloric acid gastric secretion plays, among its primary physiological foundations, a role as protective barrier against infection with external agents from the diet and also contributes to the digestion of ingested food. However, this secretion is a critical factor shared by a number of highly prevalent diseases involving the upper gastrointestinal tract. Paradigms of such conditions include gastroduodenal peptic ulcer and gastroesophageal reflux disease. PMID- 26541654 TI - Reasons for initiation of proton pump inhibitor therapy for hospitalised patients and its impact on outpatient prescription in primary care. AB - BACKGROUND: Proton-pump-inhibitors are often prescribed unnecessarily in hospitals, which in turn induces their prescriptions after discharge. OBJECTIVE: To evaluate patients starting treatment with proton-pump-inhibitors during hospitalisation and proportion of inappropriate prescriptions. Patient risk factors and whether initiation in hospital induced their continuation in ambulatory care were also analyzed. METHODS: An observational, cross-sectional study in a tertiary hospital (1350 beds) was carried out on the first Tuesday in February 2015. Pharmacists screened admitted patients treated with proton-pump inhibitors using an electronic prescription program (FarmaTools(r)-5.0). They also checked patients' home medications before admission by accessing a primary care program (Horus(r)). Authorized indications according to Spanish-Medicines Agency and those recommended in Spanish-Clinical-Practice-Guidelines were considered appropriate. Hospital-medical-records were checked to know whether proton-pump-inhibitors were prescribed at discharge. RESULTS: Three hundred seventy nine patients were analysed. Two hundred ninety four of them were prescribed proton-pump-inhibitors (77.6%). Treatment was initiated during admission for 143 patients (48.6%, 95% CI: 42.8-54.5). Of them, 91 (63.6%, 95% CI: 55.2-71.5) were inappropriate, mainly due to its inclusion unnecessarily in protocols associated with surgeries or diseases (56 cases of 91, 61.5%). Additional inappropriate indications were surgical stress ulcer prophylaxis for surgeries without bleeding risks (19.8%) and polypharmacy without drugs that increase the risk of bleeding (18.7%). Of 232 discharge reports assessed, in 153 (65.9%, 95% CI: 59.5-72), proton-pump-inhibitor continuation was recommended, of them, 51 (33.3%) were initiated at admission. CONCLUSION: In hospitalized patients there is a high prevalence of prescription of proton-pump-inhibitors unnecessarily. The superfluous use is often associated with the prescription of treatment protocols. Those treatments started in the hospital generally did not contribute to over-use existing primary care, most of them were removed at discharge. PMID- 26541655 TI - Role of colonic microbiota in colorectal carcinogenesis: a systematic review. AB - BACKGROUND AND AIM: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. METHODS: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. RESULTS: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. CONCLUSION: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer. PMID- 26541656 TI - Neomycin and bacitracin reduce the intestinal permeability in mice and increase the expression of some tight-junction proteins. AB - BACKGROUND: Tight-junction (TJ) proteins regulate paracellular permeability. Gut permeability can be modulated by commensal microbiota. Manipulation of the gut microbiota with antibiotics like bacitracin and neomycin turned out to be useful for the treatment of diarrhoea induced by Clostridium difficile or chemotherapy drugs. AIM: To evaluate the effects of the microbiota depletion evoked by the oral administration of neomycin and bacitracin on the intestinal permeability and expression of TJ proteins in mice. METHODS: Mice received neomycin and bacitracin orally for 7 days. Intestinal permeability was measured by the fluorescein isothiocyanate-dextran (FITC-dextran) method. The gene expression of TJ proteins in the intestine was determined by real time-PCR. RESULTS: FITC-dextran levels in serum were reduced by half in antibiotic-treated mice, indicating a reduction of intestinal permeability. Antibiotics increased the expression of zonula occludens 1 (ZO-1), junctional adhesion molecule A (JAM-A, and occludin in the ileum and ZO 1, claudin-3, and claudin-4 in the colon. CONCLUSION: The combination of neomycin and bacitracin reduce intestinal permeability and increase the gene expression of ZO-1, junctional adhesion molecule A (JAM-A), and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon. PMID- 26541657 TI - Small bowel obstruction due to laparoscopic barbed sutures: an unknown complication? AB - BACKGROUND: In recent years there has been an increasing uptake in the use of barbed sutures, particularly in minimally invasive and laparoscopic procedures where they may reduce operating time and improve surgical efficiency. However, little is known about the adverse events associated with these new materials and concerns have arisen regarding their safety in certain procedures. METHODS: We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database). We reveal up to 15 cases of small bowel obstruction (SBO) complicating laparoscopic pelvic surgery that have been reported to date adding two cases of SBO in our own practice following the use of barbed sutures in laparoscopic operations, both requiring surgical re-intervention in the early post-operative period. RESULTS: Fifteen similar cases of small bowel obstruction were identified, all of which occurred in patients undergoing surgery below the transverse colon . Surgical re-intervention was required in all cases although 60% of these were performed laparoscopically. CONCLUSIONS: These cases highlight that although barbed sutures provide an attractive means to allow easier and faster laparoscopic suturing, they should be used carefully in inframesocolic surgery and the suture end cut and buried to avoid inadvertent attachment to the small bowel or its mesentery. Barbed suture entanglement should be considered as an uncommon yet potentially serious differential cause for SBO presenting in the early period after laparoscopic surgery where a barbed suture has been used. PMID- 26541658 TI - Efficacy of metronidazole versus placebo in pain control after hemorrhoidectomy. Results of a controlled clinical trial. AB - INTRODUCTION: Hemorrhoidal disease occurs in 50% of people aged > 40 years and is the most common reason for anorectal surgery. Pain is the main complication. Multiple topical and systemic drugs have been investigated for pain control, but there is no ideal treatment. Metronidazole has been shown to decrease postoperative pain but is not used widely. OBJECTIVE: To evaluate the effect of oral metronidazole versus placebo and to assess postoperative pain following hemorrhoidectomy. MATERIAL AND METHODS: Controlled clinical trial in adult patients who underwent elective hemorrhoidectomy for grade III/IV hemorrhoids. Patients were assigned to receive metronidazole (500 mg q8 h orally; study group, SG) or placebo (control group, CG) for 7 days after surgery. Pain was assessed using a visual analog scale after surgery. Analgesic administration (time and use of analgesics) and resumption of daily life activities were also assessed. RESULTS: Forty-four patients were included, 22 in each group. Postoperative pain differed significantly between the SG and CG at 6 h (3.86 +/- 0.56, 6.64 +/- 1.49), 12 h (5.59 +/- 1.33, 8.82 +/- 0.79), 24 h (6.86 +/- 1.49, 9.73 +/- 0.45), day 4 (5.32 +/- 2.10, 9.50 +/- 0.59), day 7 (3.14 +/- 1.03, 7.36 +/- 1.39), and day 14 (2.14 +/- 0.46, 5.45 +/- 1.29). The first analgesia dose was required at 21.27 +/- 5.47 h in the CG and 7.09 +/- 2.36 h in the SG (p < 0.05), the time of analgesic use was 6.86 +/- 1.61 days in the CG and 13.09 +/- 2.48 days in the SG (p < 0.05), and resumption of daily activities occurred at 7.59 +/- 1.56 days in the CG and 14.73 +/- 3.76 days in the SG (p < 0.05). CONCLUSION: Oral administration of metronidazole is effective in pain management after hemorrhoidectomy. PMID- 26541659 TI - The intestinal barrier function and its involvement in digestive disease. AB - The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism. PMID- 26541660 TI - Ectopic pancreas in gallbladder. Clinical significance, diagnostic and therapeutic implications. AB - Ectopic or heterotopic pancreas is defined as the presence of pancreatic tissue in an anatomical place not related to the pancreas, being it most frequent locations the stomach and small bowel. Its finding in the gallbladder is exceptional. Since the first case was reported by Otschkin in 1916, about 30 cases have been described in literature. We report the case of a 43 years-old male patient who had an urgent laparoscopic cholecystectomy with the diagnosis of acute cholecystitis, which pathological study showed the existence of chronic cholecystitis with heterotopic pancreatic tissue in the gallbladder wall. PMID- 26541661 TI - Granulomatous appendicitis as an uncommon cause of abdominal pain. Description of a case. AB - Granulomatous appendicitis is an uncommon cause of acute abdomen. Its etiology can be infectious in nature, noninfectious or idiopathic. We present the case of a patient of whom we got to know about due to an urgent colonoscopy. At the cecum, the appendicular fold was thickened and the mucosa had erythema and nodularity. The diagnosis is made by pathology, as in the majority of cases in this entity. The surgical treatment is curative. PMID- 26541662 TI - Splenic rupture after colorectal cancer screening. AB - The number of colonoscopies performed in recent years is increasing dramatically, specially those related to colorectal cancer screening programmes. For this reason, there is a direct relationship with the number of exceptional complications such as splenic rupture. We describe a clinical case of a splenic rupture with hemodynamic instability. Consequently, an emergency splenectomy was performed 6 hours after the colonoscopy was finished. Health staff should be aware of its existence, as an early reaction will avoid more severe problems. PMID- 26541663 TI - Infarction of the greater omentum. Case report. AB - The case of a 65 year old woman presented symptoms of acute abdomen secondary to full torsion of the greater omentum is presented, diagnosed preoperatively by CT, thus avoiding emergency surgery due to good evolution with conservative attitude. This disease is a rare cause of abdominal pain, but we include it in the differential diagnosis of acute abdomen. Currently imaging techniques allow preoperative diagnosis to avoid emergency surgery, and maintain an expectant attitude to act on patient evolution. In our case, we chose conservative attitude and the patient is asymptomatic 7 months later. PMID- 26541664 TI - Unusual course of epiploic appendicitis. AB - Epiploic appendicitis is a benign and self-limited disease, due to inflammation of the epiploic appendices. The diagnosis is established by imaging techniques, avoiding treatments, interventions and unnecessary hospitalizations. Management is conservative. Complications are rare and chronicity is exceptional. PMID- 26541665 TI - Case report: Amyand's hernia, diagnosis to consider in a routine procedure. AB - Amyand hernia is a rare entity that is generally an unexpected intraoperative finding. The decision to perform prophylactic appendectomy, must take into account individual factors that may increase morbidity in a short, medium or long term future. PMID- 26541666 TI - Massive gastrointestinal pneumatosis in a patient with celiac disease and superior mesenteric artery syndrome. AB - Pneumatosis intestinalis (PI) is a radiological finding representing the presence of gas in the bowell, independently of the cause or location. We present the case of a 55-year-old man who was admitted presenting two-week history of intense vomiting. The patient was previously diagnosed with superior mesenteric artery syndrome and celiac disease. Plain x-ray and TC showed gastric and intestinal pneumatosis with important retropneumoperitoneum. Due to clinical stability the patient was managed conservatively, with a favorable outcome. PMID- 26541667 TI - Transplantation of human adipose stem cell-derived hepatocyte-like cells with restricted localization to liver using acellular amniotic membrane. AB - INTRODUCTION: Adult stem cell-derived hepatocytes transplantation holds considerable promise for future clinical individualized therapy of liver failure or dysfunction. However, the low engraftment of the available hepatocytes in the liver disease microenvironment has been a major obstacle. METHODS: Acellular human amniotic membrane was developed as a three-dimensional scaffold and combined with hepatocyte-like cells derived from human adipose stem cells to engineer a hepatic tissue graft that would allow hepatocyte engraftment in the liver effectively. RESULTS: The hepatic tissue grafts maintained hepatocyte specific gene expression and functionality in vitro. When transplanted into the surgical incision in livers for engraftment, the engineered hepatic grafts significantly decreased the degree of liver injury caused by a carbon tetrachloride treatment and generated cords that were similar to the ductal plates in the liver between the acellular human amniotic membrane and the liver of receipts at day 3 post-transplantation. The hepatic tissue grafts maintained the expression of human hepatocyte-specific markers albumin, hepatocyte nuclear factor 4alpha, and cytochrome P450 2B6 in the liver of receipts, and acquired human-specific drug metabolism ability at eight weeks post-transplantation. CONCLUSIONS: The acellular human amniotic membrane has the ability to maintain the functional phenotype of the hepatocyte-like cells derived from human adipose stem cells. Functional acellular human amniotic membrane-hepatocytes grafts integrated with the liver decreases the acute liver injury of mice. These engineered tissue constructs may support stem cell-based individualized therapy for liver disease and for bioartificial liver establishment. PMID- 26541668 TI - Point-of-care screening for syphilis and HIV in the borderlands: challenges in implementation in the Brazilian Amazon. AB - BACKGROUND: Point-of-care (POC) screening for HIV and syphilis using rapid testing was implemented in indigenous communities in the triple-border area of the Brazilian Amazon. We describe the context of the early introduction of POC screening, explore hindering and enabling factors for POC implementation, and recommend strategies for feasible, viable, and sustainable syphilis and HIV screening interventions. METHODS: This was a qualitative study based on grounded theory methodology. Data were collected using in-depth interviews, semi structured questionnaires, and field observations and were analysed using the framework approach. Qualitative information was complemented by quantitative data for descriptive purposes. RESULTS: An overall high score for vulnerability to acquiring HIV and syphilis was observed among the indigenous communities. Health professionals reported satisfactory rapid testing acceptance, although concerns were raised about the pain of the fingerprick. Counselling-related challenges included ensuring the accuracy of translations, collaborating with translators and communicating positive test results. Over 3 months, 86.7% of the syphilis positive individuals began treatment, and all of them notified their partners. Accessibility, measured as travel time via the local transportation network, was a barrier to health care access. A lack of gasoline for boats and other transportation was also a hindering factor at all levels of implementation. CONCLUSIONS: The recommendations address the preparation phase at the coordination level as well as at the training level. Tools such as strengths, weaknesses, opportunities, and threats (SWOT) analyses; checklists; context adapted protocols; and fact sheets are very simple methods to facilitate implementation. The findings of this study are important because they may inform the implementation of new health technologies in low-resource national disease control programmes in remote communities. PMID- 26541669 TI - Nutritional status of children in a malaria meso endemic area: cross sectional study on prevalence, intensity, predictors, influence on malaria parasitaemia and anaemia severity. AB - BACKGROUND: The contradictory results on the interaction between nutritional status and malaria warrants further investigation in various epidemiological settings, to assert the antagonistic or synergistic relationship. This study examines the prevalence, severity and predictors of malnutrition and its influence on malaria parasitaemia and anaemia severity in children in the Mount Cameroon area. METHODS: A cross-sectional study involving 454 children <= 14 years was carried out from February to May 2013 in Muea community. Anthropometric measures of malnutrition (z-scores < -2 standard deviations below mean) were obtained and spleen size assessed. The prevalence and density of malaria parasites were determined and haemoglobin concentration and white blood cell count obtained using an automated haematology analyzer. Univariate and multivariate analyses were used to evaluate influence of malnutrition on anaemia, malaria parasitaemia and predictors respectively. RESULTS: The overall prevalence of malnutrition was 22.8 %, with stunting being the most common form (17.1 %), followed by underweight (8.2 %) and wasting (5.5 %). Stunting was significantly higher (P < 0.01) in males (23.1 %) than in females (11.9 %). The prevalence of malnutrition was significantly highest (P = 0.03) in children <=5 years old (29.5 %) than their counterparts. Severe stunting, wasting and underweight were prevalent in 4.9 %, 1.6 % and 1.8 % of the children respectively. Clinical malaria parasitaemia was significantly higher (P = 0.01) in children who were stunted (16.9 %) and underweight (21.6 %) than their normal counterparts (7.5 %; 8.2 % respectively). The model demonstrated sex (P = 0.006) and age group 1.1-3 years (P = 0.03) as significant predictors of malnutrition. In children who were malaria parasite negative, the prevalence of anaemia as well as severities were significantly higher (P = 0.04 and P = 0.001 respectively) in those malnourished. CONCLUSIONS: The presence of stunting in the community significantly augmented the prevalence and clinical presentation of Plasmodium infection. Malnutrition enhanced the severity of anaemia in malaria parasite negative children hence, their health and growth potential needs to be improved upon. PMID- 26541670 TI - IL-10 regulate decidual Tregs apoptosis contributing to the abnormal pregnancy with Toxoplasma gondii infection. AB - This study aims to investigate whether IL-10 regulate decidual Treg cells apoptosis to reverse the abnormal pregnancy outcomes with Toxoplasma gondii (T. gondii) infection. Recombinant mouse IL-10 (rIL-10) treatment and IL-10 deficiency (IL-10(-/-)) abnormal pregnancy animal models with T. gondii infection were established. Apoptosis related molecules cleaved Caspase-3 and Caspase-8 in decidual Treg cells were examined using flow cytometry. The levels of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were up-regulated with T. gondii infection. Compared to infected group, the expressions of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were down-regulated in rIL-10-treated group, while up-regulated in infected IL-10(-/-) group. In addition, pregnant outcomes were improved in rIL-10-treated group, while worse in IL-10(-/-) group compared to infected group. These findings revealed that IL-10 reduced the decidual Treg cells apoptosis contributing to improving adverse pregnant outcomes following T. gondii infection. PMID- 26541671 TI - Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood. AB - Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-kappaB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-kappaB were activated only at 60 and 180 min post injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-kappaB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease pathogenesis. PMID- 26541672 TI - Bacterial interactions in pathogenic subgingival plaque. AB - Chronic periodontitis has a polymicrobial biofilm aetiology. Polymicrobial biofilms are complex, dynamic microbial communities formed by two or more bacterial species that are important for the persistence and proliferation of participating microbes in the environment. Interspecies adherence, which often involves bacterial surface-associated molecules, and communications are essential in the spatial and temporal development of a polymicrobial biofilm, which in turn is necessary for the overall fitness of a well-organized multispecies biofilm community. In the oral cavity, interactions between key oral bacterial species, including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, are essential for the progression of chronic periodontitis. In vivo, P. gingivalis and T. denticola are frequently found to co-exist in deep periodontal pockets and have been co-localized to the superficial layers of subgingival plaque as microcolony blooms adjacent to the pocket epithelium, suggesting possible interbacterial interactions that contribute towards disease. The motility and chemotactic ability of T. denticola, although not considered as classic virulence factors, are likely to be important in the synergistic biofilm formation with P. gingivalis. In vitro, P. gingivalis and T. denticola display a symbiotic relationship in nutrient utilization and growth promotion. Together these data suggest there is an intimate relationship between these two species that has evolved to enhance their survival and virulence. PMID- 26541673 TI - Multivariate assessment of event-related potentials with the t-CWT method. AB - BACKGROUND: Event-related brain potentials (ERPs) are usually assessed with univariate statistical tests although they are essentially multivariate objects. Brain-computer interface applications are a notable exception to this practice, because they are based on multivariate classification of single-trial ERPs. Multivariate ERP assessment can be facilitated by feature extraction methods. One such method is t-CWT, a mathematical-statistical algorithm based on the continuous wavelet transform (CWT) and Student's t-test. RESULTS: This article begins with a geometric primer on some basic concepts of multivariate statistics as applied to ERP assessment in general and to the t-CWT method in particular. Further, it presents for the first time a detailed, step-by-step, formal mathematical description of the t-CWT algorithm. A new multivariate outlier rejection procedure based on principal component analysis in the frequency domain is presented as an important pre-processing step. The MATLAB and GNU Octave implementation of t-CWT is also made publicly available for the first time as free and open source code. The method is demonstrated on some example ERP data obtained in a passive oddball paradigm. Finally, some conceptually novel applications of the multivariate approach in general and of the t-CWT method in particular are suggested and discussed. CONCLUSIONS: Hopefully, the publication of both the t-CWT source code and its underlying mathematical algorithm along with a didactic geometric introduction to some basic concepts of multivariate statistics would make t-CWT more accessible to both users and developers in the field of neuroscience research. PMID- 26541674 TI - Desmopressin in adult urological disease: clinical evidences. AB - Desmopressin is a synthetic analogue of arginine vasopressin, commercially available since 1974. Desmopressin is proven effective for the treatment primary nocturnal enuresis and polyuria. It has been considered by several investigators for the treatment of nocturia with positive results and is now an established treatment for this indication. In this review, we assessed the available clinical data on desmopressin in adult urological disease. PMID- 26541675 TI - Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression. AB - BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide, mainly due to late diagnosis, poor prognosis and tumor heterogeneity. Thus, the need for biomarkers that will aid classification, treatment and monitoring remains intense and challenging and depends on the better understanding of the tumor pathobiology and underlying mechanisms. The deregulation of gene expression is a hallmark of cancer and a critical parameter is the stability of mRNAs that may lead to increased oncogene and/or decreased tumor suppressor transcript and protein levels. The shortening of mRNA poly(A) tails determines mRNA stability, as it is usually the first step in mRNA degradation, and is catalyzed by deadenylases. Herein, we assess the clinical significance of deadenylases and we study their role on gene expression in squamous cell lung carcinoma (SCC). METHODS: Computational transcriptomic analysis from a publicly available microarray was performed in order to examine the expression of deadenylases in SCC patient samples. Subsequently we employed real-time PCR in clinical samples in order to validate the bioinformatics results regarding the gene expression of deadenylases. Selected deadenylases were silenced in NCI-H520 and Hep2 human cancer cell lines and the effect on gene expression was analyzed with cDNA microarrays. RESULTS: The in silico analysis revealed that the expression of several deadenylases is altered in SCC. Quantitative real-time PCR showed that four deadenylases, PARN, CNOT6, CNOT7 and NOC, are differentially expressed in our SCC clinical samples. PARN overexpression correlated with younger patient age and CNOT6 overexpression with non-metastatic tumors. Kaplan-Meier analysis suggests that increased levels of PARN and NOC correlate with significantly increased survival. Gene expression analysis upon PARN and NOC silencing in lung cancer cells revealed gene expression deregulation that was functionally enriched for gene ontologies related to cell adhesion, cell junction, muscle contraction and metabolism. CONCLUSIONS: Our results highlight the clinical significance of PARN and NOC on the survival in SCC diagnosed patients. We demonstrate that the enzymes are implicated in important phenotypes pertinent to cancer biology and provide information on their role in the regulation of gene expression in SCC. Overall, our results support an emerging role for deadenylases in SCC and contribute to the understanding of their role in cancer biology. PMID- 26541676 TI - Dextrocardia in Adults with Congenital Heart Disease. AB - BACKGROUND/OBJECTIVES: Dextrocardia is rare in the general population, and may be associated with significant additional cardiac malformations. We aimed to identify the prevalence and patterns of additional cardiac defects, as well as the associated long-term morbidity and mortality, in adult patients with dextrocardia, in a specialised Adult Congenital Heart Disease (ACHD) service. METHODS: A retrospective study of patients with dextrocardia managed by our tertiary ACHD service, since January 2000, was performed. Medical records were reviewed and the National Death Index was consulted to confirm survival status. RESULTS: Of 3698 adults in our ACHD Service, 19 (0.5%) had dextrocardia. Mean follow-up duration was 7+/-7.5 years. The mean age at last review was 36.8+/-10.5 years (range 20-63 years). Situs was solitus in 14 (74%) and inversus in five (26%). Eleven patients (58%) had functional single ventricles, of whom five had atrioventricular (AV)-ventriculoarterial (VA) discordance and two had VA discordance only. Four patients with two ventricles had AV-VA discordance. All patients had at least one additional cardiac malformation. Fourteen patients (74%) required surgical intervention. Eleven patients (58%) underwent a Fontan type operation. Five patients (26%) required ablation procedures for arrhythmia. One patient had infective endocarditis and two deaths occurred, both in patients who also had AV-VA discordance. CONCLUSION: Dextrocardia remains a rare finding in adults, even in a highly select group of patients with known congenital heart disease. Those with associated congenital heart abnormalities are likely to have complex lesions, which may require multiple surgical and medical interventions. Despite this, our series demonstrated that patients surviving to adulthood and then managed in an ACHD centre may have good medium-term survival. PMID- 26541677 TI - The elusive philosopher's stone in young blood. PMID- 26541678 TI - How an artery heals. PMID- 26541679 TI - Breaking down the COP9 Signalsome in the heart: how inactivating a protein ubiquitin ligase increases protein ubiquitylation and protects the heart. PMID- 26541680 TI - Walter J. Koch: two decades, one mission. PMID- 26541682 TI - Correction. PMID- 26541681 TI - Murine "model" monotheism: an iconoclast at the altar of mouse. PMID- 26541683 TI - Correction. PMID- 26541684 TI - Epidemiology and resource utilization in pediatric facial fractures. AB - BACKGROUND: Pediatric facial fractures, although uncommon, have a significant impact on public health and the US economy by the coexistence of other injuries and developmental deformities. Violence is one of the most frequent mechanisms leading to facial fracture. Teaching hospitals, while educating future medical professionals, have been linked to greater resource utilization in differing scenarios. This study was designed to compare the differences in patient characteristics and outcomes between teaching and non-teaching hospitals for violence-related pediatric facial fractures. METHODS: Using the 2000-2009 Kids' Inpatient Database, 3881 patients younger than 18 years were identified with facial fracture and external cause of injury code for assault, fight, or abuse. Patients admitted at teaching hospitals were compared to those admitted at non teaching hospitals in terms of demographics, injuries, and outcomes. RESULTS: Overall, 76.2% of patients had been treated at teaching hospitals. Compared to those treated at non-teaching hospitals, these patients were more likely to be younger, non-white, covered by Medicaid, from lower income zip codes, and have thoracic injuries; but mortality rate was not significantly different. After adjusting for potential confounders, teaching status of the hospital was not found as a predictor of either longer lengths of stay (LOS) or charges. CONCLUSIONS: There is an insignificant difference between LOS and charges at teaching and non-teaching hospitals after controlling for patient demographics. This suggests that the longer LOS observed at teaching hospitals is related to these institutions being more often involved in the care of underserved populations and patients with more severe injuries. PMID- 26541685 TI - Preoperative consent for patients with limited English proficiency. AB - BACKGROUND: Informed consent is important for limited English proficient (LEP) patients undergoing surgery, as many surgical procedures are complicated, making patient comprehension difficult even without language barriers. The study objectives were to (1) understand surgeons' preoperative consenting process with LEP patients, (2) examine how surgeons self assess their non-English language proficiency levels using a standardized scale, and (3) identify the relationship between self assessed non-English language proficiency and surgeons' self reported use of interpreters during preoperative informed consent. MATERIALS AND METHODS: A thirty-two item survey assessing surgeons' reported preoperative informed consent process, with questions related to demographics, level of medical training, non-English language skills and their clinical use, language learning experiences, and hypothetical scenarios with LEP patients. RESULTS: Surgeons who were not fluent in non-English languages reported they often used those limited skills to obtain informed consent from their LEP patients. Many surgeons reported relying on bilingual hospital staff members, family members, and/or minors to serve as ad-hoc interpreters when obtaining informed consent. If a professional interpreter was not available in a timely manner, surgeons more frequently reported using ad-hoc interpreters or their own nonfluent language skills. Surgeons reported deferring to patient and family preferences when deciding whether to use professional interpreters and applied different thresholds for different clinical scenarios when deciding whether to use professional interpreters. CONCLUSIONS: Surgeons reported relying on their own non-English language skills, bilingual staff, and family and friends of patients to obtain informed consent from LEP patients, suggesting that further understanding of barriers to professional interpreter use is needed. PMID- 26541686 TI - Smoking and wound complications after coronary artery bypass grafting. AB - BACKGROUND: The harmful effects of smoking on the postsurgical wound healing disturbances have been widely investigated across various surgical procedures. These effects after coronary artery bypass graft (CABG) surgery have been less explored. We aimed to investigate the association of smoking and the wound healing problems in post-CABG patients. MATERIALS AND METHODS: We compared the incidence of wound complications in 405 smokers and 405 nonsmokers who underwent an elective CABG surgery. The incidence of leg and sternal wound complications was evaluated during the first 7 d as well as at a 6-wk postoperative visit. RESULTS: One hundred fifty-six leg wound complications were noted in 132 patients (16.3%). The overall rate of leg wound healing disturbances was significantly higher in smokers than those in nonsmokers (odds ratio, 1.47; 95% confidence interval, 1.109-4.019; P = 0.010). The incidence rates of leg wound edge necrosis and dehiscence were significantly higher in smokers compared with those in nonsmokers (3.7% versus 0.7%, P = 0.004 and 6.6% versus 0.7%, P < 0.0001, respectively). We found no significant differences between the incidence of postoperative leg wound infection, hematoma, wound edema, and seroma in active smokers and those who never smoked. Thirty-seven postsurgical sternal wound complications (4.6%) were developed in 33 patients (4.1%). The overall rate of sternal wound healing disturbances was similar between smokers and nonsmokers. There was a trend between the sternal wound dehiscence and smoking (P = 0.03); however, the other sternal wound complications were not associated with smoking. CONCLUSIONS: Smoking may contribute to the disturbances of wound healing, especially wound dehiscence, in post-CABG patients. PMID- 26541687 TI - The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees: pragmatic randomised controlled clinical trial. AB - BACKGROUND: Little evidence exists on the treatment of traumatised refugees. AIMS: To estimate treatment effects of flexible cognitive-behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees. METHOD: Randomised controlled clinical trial with 2 * 2 factorial design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months. RESULTS: A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression. CONCLUSIONS: In a pragmatic clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to moderate effect of antidepressants and psychoeducation on depression in traumatised refugees. PMID- 26541688 TI - Visual cortical excitability in dementia with Lewy bodies. AB - Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1-3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations. PMID- 26541689 TI - CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder. AB - Several genome-wide association studies and case-control studies have associated the single nucleotide polymorphism (SNP) rs1006737, situated in CACNA1C encoding the alpha 1C subunit of the L-type voltage-gated calcium channel, with bipolar disorder and other psychiatric disorders. However, the causal pathway linking genetic variants in CACNA1C with increased risk for developing brain disorders remains unclear. Here, we explored the association between the rs1006737 SNP and cerebrospinal fluid (CSF) markers. We found a significant association between the risk allele in rs1006737 and a decreased CSF hyperphosphorylated tau/total tau ratio in patients with bipolar disorder, thus linking variation in the CACNA1C gene to a neurochemical marker of neuroaxonal plasticity in those with this disorder. PMID- 26541690 TI - Substance misuse in life and death in a 2-year cohort of suicides. AB - BACKGROUND: Although substance misuse is a key risk factor in suicide, relatively little is known about the relationship between lifetime misuse and misuse at the time of suicide. AIMS: To examine the relationship between substance misuse and subsequent suicide. METHOD: Linkage of coroners' reports to primary care records for 403 suicides occurring over 2 years. RESULTS: With alcohol misuse, 67% of the cohort had previously sought help for alcohol problems and 39% were intoxicated at the time of suicide. Regarding misuse of other substances, 54% of the cohort was tested. Almost one in four (38%) tested positive, defined as an excess of drugs over the prescribed therapeutic dosage and/or detection of illicit substances. Those tested were more likely to be young and have a history of drug misuse. CONCLUSIONS: A deeper understanding of the relationship between substance misuse and suicide could contribute to prevention initiatives. Furthermore, standardised toxicology screening processes would avoid diminishing the importance of psychosocial factors involved in suicide as a 'cause of death'. PMID- 26541691 TI - Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis. AB - We assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis. PMID- 26541693 TI - Premature mortality in autism spectrum disorder. AB - BACKGROUND: Mortality has been suggested to be increased in autism spectrum disorder (ASD). AIMS: To examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability. METHOD: Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27,122, diagnosed between 1987 and 2009) compared with gender-, age and county of residence-matched controls (n = 2,672,185). RESULTS: During the observed period, 24,358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38-2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause specific mortality were partly moderated by gender and general intellectual ability. CONCLUSIONS: Premature mortality was markedly increased in ASD owing to a multitude of medical conditions. PMID- 26541692 TI - Functional remediation in bipolar disorder: 1-year follow-up of neurocognitive and functional outcome. AB - BACKGROUND: Few randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder. AIMS: To examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline. METHOD: This was a multicentre, randomised, rater-masked clinical trial comparing three patient groups: functional remediation, psychoeducation and treatment as usual over 1-year follow-up. The primary outcome was change in psychosocial functioning measured by means of the Functioning Assessment Short Test (FAST). Group*time effects for overall psychosocial functioning were examined using repeated measures ANOVA (trial registration NCT01370668). RESULTS: There was a significant group*time interaction for overall psychosocial functioning, favouring patients in the functional remediation group (F = 3.071, d.f. = 2, P = 0.049). CONCLUSIONS: Improvement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation. PMID- 26541694 TI - Radiological findings of a symptomatic carotid pseudocclusion: "Guadiana river sign". PMID- 26541695 TI - Health-related quality of life in patients with spinocerebellar ataxia. AB - INTRODUCTION: The progressive deterioration of patients with spinocerebellar ataxia (SCA) has a major impact on their health-related quality of life (HRQOL). This study evaluates HRQOL in a sample of patients diagnosed with SCA and aims to estimate the predictive ability of a set of sociodemographic variables for the different dimensions of the General Health Questionnaire. METHODS: A total of 80 patients diagnosed with SCA were assessed using a sociodemographic questionnaire and the SF-36 General Health Questionnaire. The sociodemographic variables studied were sex, age, presence of a carer, employment status, and time elapsed from diagnosis of the disease. RESULTS: The 8 subscales of the SF-36 show positive and significant correlations to one another. Mean scores obtained on each SF-36 subscale differ between women and men, although this difference is significant only on the general health subscale, with men scoring higher than women. We found significant age differences on the vitality and social function subscales, with higher scores among younger patients (< 34 years). The variable 'presence of a carer' accounts for most of the total variance of the questionnaire. CONCLUSIONS: The SF-36 is a valid and useful instrument for evaluating HRQOL in patients diagnosed with SCA. Presence of a carer seems to be a determinant of self-perceived quality of life in these patients. PMID- 26541696 TI - Descriptive analysis of neurological in-hospital consultations in a tertiary hospital. AB - INTRODUCTION: In-hospital consultations (IHC) are essential in clinical practice in tertiary hospitals. The aim of this study is to analyse the impact of neurological IHCs. PATIENTS AND METHOD: One-year retrospective descriptive study of neurological IHCs conducted from May 2013 to April 2014 at our tertiary hospital. RESULTS: A total of 472 patients were included (mean age, 62.1 years; male patients, 56.8%) and 24.4% had previously been evaluated by a neurologist. Patients were hospitalised a median of 18 days and 19.7% had been referred by another hospital. The departments requesting the most in-hospital consultations were intensive care (20.1%), internal medicine (14.4%), and cardiology (9.1%). Reasons for requesting an IHC were stroke (26.9%), epilepsy (20.6%), and confusional states (7.6%). An on-call neurologist evaluated 41.9% of the patients. The purpose of the IHC was to provide a diagnosis in 56.3% and treatment in 28.2% of the cases; 69.5% of the patients required additional tests. Treatment was adjusted in 18.9% of patients and additional drugs were administered to 27.3%. While 62.1% of cases required no additional IHCs, 11% required further assessment, and 4.9% were transferred to the neurology department. Of the patient total, 16.9% died during hospitalisation (in 37.5%, the purpose of the consultation was to certify brain death); 45.6% were referred to the neurology department at discharge and 6.1% visited the emergency department due to neurological impairment within 6 months of discharge. CONCLUSIONS: IHCs facilitate diagnosis and management of patients with neurological diseases, which may help reduce the number of visits to the emergency department. On-call neurologists are essential in tertiary hospitals, and they are frequently asked to diagnose brain death. PMID- 26541697 TI - Hyperammonemic encephalopathy associated with multiple myeloma. PMID- 26541698 TI - Relaxin: A novel therapy for acute heart failure. PMID- 26541699 TI - Access to side-chain carbon information in deuterated solids under fast MAS through non-rotor-synchronized mixing. AB - We demonstrate the accessibility of aliphatic (13)C side chain chemical shift sets for solid-state NMR despite perdeuteration and fast MAS using isotropic, non rotor-synchronized (13)C-(13)C mixing. Combined with amide proton detection, we unambiguously and sensitively detect whole side chain to backbone correlations for two proteins using around 1 mg of sample. PMID- 26541700 TI - Overemphasis on Overdiagnosis. PMID- 26541701 TI - The "Unconference" in Radiological Society Meetings. PMID- 26541702 TI - Psychological stress-induced catecholamines accelerates cutaneous aging in mice. AB - Psychological stress may be an important extrinsic factor which influences aging process. However, neither study demonstrated the mechanism by which chronic stress participates in skin aging. Aim of this study was to investigate the effects of chronic psychological stress on mice skin. Mice were daily submitted to rotational stress, for 28 days, until euthanasia. After 28 days, mice were killed and normal skin was analyzed. Macroscopically, dorsum skin of chronically stressed mice presented more wrinkled when compared to that of nonstressed mice. In mice skin, chronic stress increased lipid peroxidation, carbonyl protein content, nitrotyrosine levels, neutrophil infiltration, neutrophil elastase, tissue inhibitor of metalloproteinase-1 and metalloproteinase-8 levels. Nevertheless, chronic stress reduced dermis thickness, collagen type I, fibrilin 1 and elastin protein levels in mice skin. In in vitro assays, murine skin fibroblasts were exposed to elevated epinephrine levels plus inhibitors of reactive oxygen species (ROS) and reactive nitrogen species (RNS), fibroblast activity was evaluated in a short time. In skin fibroblast culture, treatment with inhibitors of ROS and RNS synthesis abolished the increase in carbonyl protein content and lipid peroxide accumulation induced by epinephrine. In conclusion, chronic psychological stress may be an important extrinsic factor, which contributes to skin aging in mice. PMID- 26541703 TI - [Ectopic Kidney. A diagnostic case]. PMID- 26541704 TI - [Possibility of scoliosis screening and prevention in schools]. PMID- 26541705 TI - [Cutaneous mastocytosis: A case report]. AB - INTRODUCTION: Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. OBJECTIVE: To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. CLINICAL CASE: A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. CONCLUSIONS: Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment. PMID- 26541707 TI - Pathophysiology of acute heart failure: a world to know. AB - Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease. PMID- 26541706 TI - Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. AB - Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet generation, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 decades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug (i.e. the first wave of hemostasis). Activated platelets can also provide negatively charged phosphatidylserinerich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation (i.e. the second wave of hemostasis). Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen independent platelet aggregation and thrombosis, and the plasma fibronectin mediated "protein wave" of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflammation and atherosclerosis and the potential strategies to control atherothrombosis. PMID- 26541708 TI - Semaphorin 3a transfection into the left stellate ganglion reduces susceptibility to ventricular arrhythmias after myocardial infarction in rats. AB - AIMS: Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. METHODS AND RESULTS: Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. CONCLUSION: Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis. PMID- 26541709 TI - Radiofrequency ablation of the interventricular septum to treat outflow tract gradients in hypertrophic obstructive cardiomyopathy: a novel use of CARTOSound(r) technology to guide ablation. AB - AIMS: Septal reduction is needed for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow tract (LVOT) gradients and symptoms despite medication. Myectomy cannot be performed in all. Alcohol septal ablation cannot be performed in 5-15% due to technical difficulties. A method of delivering percutaneous tissue damage to the septum that is not reliant on coronary anatomy is desirable. To directly ablate the interventricular septum at the mitral valve (MV) systolic anterior motion (SAM)-septal contact point using radiofrequency (RF) energy guided by CARTOSound. METHODS AND RESULTS: Five patients underwent RF ablation (RFA); we describe follow-up at 6 months in four patients. Intracardiac echocardiography (ICE) images are merged with CARTO to create a shell of the cardiac chambers. The SAM-septal contact area is marked from ICE images and mapped on to the CARTO shell; this becomes the target for RF delivery. Conduction tissue is mapped and avoided where possible. Twenty-eight to 42 min of RF energy was delivered to the target area using retrograde aortic access and SmartTouch catheters. Resting LVOT gradient improved from 64.2 (+/ 50.6) to 12.3 (+/-2.5) mmHg. Valsalva/exercise-induced gradient reduced from 93.5 (+/-30.9) to 23.3 (+/-8.3) mmHg. Three patients improved New York Heart Association status from III to II, one patient improved from class III to I. Exercise time on bicycle ergometer increased from 612 to 730 s. Cardiac magnetic resonance shows late gadolinium enhancement up to 8 mm depth at LV target myocardium. One patient died following a significant retroperitoneal haemorrhage. CONCLUSION: Radiofrequency ablation using CARTOSound((r)) guidance is accurate and effective in treating LVOT gradients in HOCM in this preliminary group of patients. PMID- 26541710 TI - Clustering of worry appraisals among college students. AB - The present study investigated the potential clustering of worry appraisals within college social networks. Participants living in campus residence buildings responded to online surveys across the course of several months. Worry appraisals were measured 10 weeks into the fall semester and again approximately 6 months later. Analysis of sociometric data suggests that the majority of participants' social interactions occurred within their respective residence building floors, indicating that proximity strongly influenced the development of social network ties and sources of social influence. Further, significant clustering of worry appraisals occurred across time, and more importantly, within residence building floors. The present findings compliment previous work suggesting that several physical and psychological states appear to spread and cluster within social networks. Implications for the study of emotional appraisals and future research are discussed. PMID- 26541711 TI - Free-breathing 3D diffusion MRI for high-resolution hepatic metastasis characterization in small animals. AB - The goal of this study was to develop a 3D diffusion weighted sequence for free breathing liver imaging in small animals at high magnetic field. Hepatic metastases were detected and the apparent diffusion coefficients (ADC) were measured. A 3D SE-EPI sequence was developed by (i) inserting a water-selective excitation radiofrequency pulse to suppress adipose tissue signal and (ii) bipolar diffusion gradients to decrease the sensitivity to respiration motion. Mice with hepatic metastases were imaged at 7T by applying b values from 200 to 1100 s/mm(2). 3D images with high spatial resolution (182 * 156 * 125 um) were obtained in only 8 min 32 s. The modified DW-SE-EPI sequence allowed to obtain 3D abdominal images of healthy mice with fat SNR 2.5 times lower than without any fat suppression method and sharpness 2.8 times higher than on respiration triggered images. Due to the high spatial resolution, the core and the periphery of disseminated hepatic metastases were differentiated at high b-values only, demonstrating the presence of edema and proliferating cells (with ADC of 2.65 * 10(-3) and 1.55 * 10(-3) mm(2)/s, respectively). Furthermore, these metastases were accurately distinguished from proliferating ones within the same animal at high b-values (mean ADC of 0.38 * 10(-3) mm(2)/s). Metastases of less than 1.7 mm(3) diameter were detected. The new 3D SE-EPI sequence enabled to obtain diffusion information within liver metastases. In addition of intra-metastasis heterogeneity, differences in diffusion were measured between metastases within an animal. This sequence could be used to obtain diffusion information at high magnetic field. PMID- 26541712 TI - Supraglottoplasty as treatment of exercise induced laryngeal obstruction (EILO). AB - Breathing difficulties during exertion may be caused by exercise-induced laryngeal obstruction (EILO). The diagnosis depends on visualization of the larynx during exercise, i.e. by continuous laryngoscopic exercise (CLE) test. In case of severe supraglottic collapse and pronounced symptoms during strenuous exertion, surgical treatment (supraglottoplasty) has been suggested. The aims of this study were to evaluate outcome and patient satisfaction after supraglottoplasty for EILO and to compare our results with previously reported data. During the period December 2010 to October 2013, 17 patients diagnosed with moderate to severe supraglottic EILO were treated by supraglottoplasty with microlaryngoscopic laser technique at our institutions. The severity of patients symptoms (VAS score) and CLE scores was evaluated pre- and postoperatively. We found a decrease in patients symptoms from median 80 points VAS score preoperatively to 20 points postoperatively (p < 0.001) and a decrease in CLE sum score from median 4.0 points to 2.5 points (p < 0.05). Several previous studies have recommended surgery for selected patients with supraglottic involvement, but these have mainly been based on case reports or on very few patients. This study is the second larger-scale study that documents the positive effect of supraglottoplasty as treatment of EILO in terms of reduced respiratory symptoms and decreased laryngeal obstruction assessed by post-operative CLE test. We suggest that surgery is a well-tolerated and effective treatment option for selected EILO patients with moderate to severe supraglottic obstruction during exercise and a high level of physical activity. PMID- 26541713 TI - Erratum to: Stability, survival, and tolerability of a 4.5-mm-wide bone-anchored hearing implant: 6-month data from a randomized controlled clinical trial. PMID- 26541714 TI - Expansion sphincter pharyngoplasty for the treatment of OSA: a systemic review and meta-analysis. AB - This study seeks to determine the success rates of the expansion sphincter pharyngoplasty and its variants on the treatment of obstructive sleep apnea (OSA). Systematic review and meta-analysis. Two independent searches of MEDLINE, Google Scholar, Cochrane Library and Evidence Based Medicine Reviews to identify publications relevant to OSA and expansion pharyngoplasty. All relevant studies published before 31 March 2015 were included. Five studies were included in the systematic review and meta-analysis. The numbers of patients in each paper ranged from 10 to 85 (total = 155), and mean age ranged from 8 to 56 years. Substantial and consistent improvement in PSG outcomes were observed post-expansion pharyngoplasty patients, with or without multilevel surgery groups. The results showed that the expansion pharyngoplasty technique has significantly lower AHI than control group [Standardised mean difference -7.32, 95 %CI (-11.11, -3.52), p = 0.0002]; however, substantial heterogeneity between these studies were observed. The mean pre-operative AHI (in the five papers) improved from 40.0 +/- 12.6 to 8.3 +/- 5.2 post-operatively. The overall pro-rated pooled success rate for all the patients was 86.3 %. The expansion pharyngoplasty is effective in the management of patients with OSA. PMID- 26541715 TI - Computed tomography-based training model for otoplasty. AB - Otoplasty for the correction of protruding ears is characterized by various techniques and a common and popular cosmetic procedure. For the surgeon, whether beginner or advanced, it is essential to understand the principles and master techniques for standard auricular deformities before applying further sophisticated methods, because a lot of complications and failures are caused by wrong indication and incorrect surgical techniques. The different surgical steps are best learned from teaching models. Therefore, we developed two different silicone models of protruding ears with moderate auricular deformities: one with conchal hyperplasia for the training of conchal resection, and one without antihelix for creating an antihelical fold by suturing technique, based on computed tomography scans of patients. The silicone ear models were evaluated during four standardized surgery courses for residents in otorhinolaryngology by 91 participants using specially designed questionnaires. Nearly all participants rated the training on the auricular models as very helpful (n = 51) or good (n = 31); the scores for the different techniques and properties of the models ranged from 2.0 to 2.6 in a range from 1 (very good) to 4 (inadequate). The good results demonstrate the possibility for learning different surgical otoplasty techniques with this newly designed teaching tool. PMID- 26541716 TI - "Re. 'Early oral refeeding based on hunger in moderate and severe acute pancreatitis: A prospective controlled, randomized clinical trial.' Can we really do without enteral nutrition?" Author's response. PMID- 26541717 TI - Association of conjugated linoleic acid consumption and liver enzymes in human studies: A systematic review and meta-analysis of randomized controlled clinical trials. AB - OBJECTIVE: The aim of this study was to systematically review the association of conjugated linoleic acid (CLA) consumption in two forms of foods enriched or supplemented with CLA on serum liver enzymes in human studies. METHODS: We searched PubMed, Google Scholar, Cochrane Library, ScienceDirect, ProQuest, and Ovid up to January 2015. Studies that examined the effect of CLA supplementation or foods enriched with CLA on liver enzymes concentrations among healthy adults were included. The mean difference and SD of changes in serum liver enzymes between the intervention and control groups were used as effect size for the meta analysis. RESULTS: The analysis demonstrated that CLA supplementation led to slight and nonsignificant decreases in alkaline phosphatase (ALP) levels (mean difference [MD] -0.216; 95% confidence interval [CI], -0.60 to 0.17; P = 0.28). CLA intake can nonsignificantly increase alanine transaminase (ALT) levels (MD = 0.107 U/L; 95% CI, -0.29 to 0.244; P = 0.124) and can significantly increase aspartate aminotransferase (AST) levels (MD = 0.171 U/L; 95% CI, 0.034-0.307; P = 0.01). Subgroup analysis based on CLA source showed that CLA supplementation or foods enriched with CLA did not significantly alter ALT levels. Subgroup analysis showed that CLA supplementation led to significant increases in AST levels (MD = 0.224 U/L; 95% CI, 0.071-0.376; P = 0.004). However, foods enriched with CLA did not have any significant effects on AST levels. CONCLUSION: CLA supplementation was associated with a significantly increased circulating AST without any significant effect on ALP and ALT levels. Prospective studies are necessary to assess the clinical outcomes of the association between CLA and liver enzyme concentrations. PMID- 26541718 TI - Corrigendum to . PMID- 26541719 TI - Avermectin induced autophagy in pigeon spleen tissues. AB - The level of autophagy is considered as an indicator for monitoring the toxic impact of pesticide exposure. Avermectin (AVM), a widely used insecticide, has immunotoxic effects on the pigeon spleen. The aim of this study was to investigate the status of autophagy and the expression levels of microtubule associated protein1 light chain 3 (LC3), beclin-1, dynein, autophagy associated gene (Atg) 4B, Atg5, target of rapamycin complex 1 (TORC1) and target of rapamycin complex 2 (TORC2) in AVM-treated pigeon spleens. Eighty two-month-old pigeons were randomly divided into four groups: a control group, a low-dose group, a medium-dose group and a high-dose group, which were fed a basal diet spiked with 0, 20, 40 and 60 mg AVM/kg diet, respectively. Microscopic cellular morphology revealed a significant increase in autophagic structures in the AVM treated groups. The expression of LC3, beclin-1, dynein, Atg4B and Atg5 increased, while mRNA levels of TORC1 and TORC2 were decreased in the AVM-treated groups relative to the control groups at 30, 60 and 90 days in the pigeon spleen. These results indicated that AVM exposure could up-regulate the level of autophagy in a dose-time-dependent manner in the pigeon spleen. PMID- 26541721 TI - Current practices in biliary surgery: Do we practice what we teach? AB - INTRODUCTION: Since the widespread adoption of laparoscopic techniques in biliary surgery, the incidence of bile duct injures (BDI) has not significantly declined despite increased operative experience and recognition of the critical view of safety (CVS) method for anatomic identification. We hypothesized that operative approaches in clinical practice may vary from well-described technical recommendations. The objective of this study was to access how practicing surgeons commonly identify anatomy during laparoscopic cholecystectomy (LC). METHODS: We performed a cohort study assessing practices in biliary surgery among current practicing surgeons. Surgeons belonging to the Midwest Surgical Association and the Society of American Gastrointestinal and Endoscopic Surgeons were surveyed. Items surveyed include preferred methods for cystic duct identification, recognition of the CVS, and use of intraoperative imaging. RESULTS: In total, 374 of 849 surgeons responded. The CVS was not correctly identified by 75 % of surgeons descriptively and by 21 % of surgeons visually. 56 % of surgeons practiced the infundibular method for identification of the cystic duct; 27 % practiced the CVS method. Intraoperative cholangiography was used by 16 % and laparoscopic ultrasound by <1 %. CONCLUSION: A majority of surgeons preferably do not use the CVS method of identification during LC. A large percentage of practicing surgeons are unable to describe or visually identify the CVS. These results suggest an urgent need to reexamine the tenets of how LC is being taught and disseminated and present a clear target for improvement to reduce BDI. PMID- 26541720 TI - Impact of novel shift handle laparoscopic tool on wrist ergonomics and task performance. AB - BACKGROUND: Laparoscopic tool handles causing wrist flexion and extension more than 15 degrees from neutral are considered "at risk" for musculoskeletal strain. Therefore, this study measured the impact of laparoscopic tool handle angles on wrist postures and task performance. METHODS: Eight surgeons performed standard and modified Fundamentals of Laparoscopic Surgery (FLS) tasks with laparoscopic tools. Tool A had three adjustable handle angle configurations, i.e., in-line 0 degrees (A0), 30 degrees (A30), and pistol-grip 70 degrees (A70). Tool B was a fixed pistol-grip grasper. Participants performed FLS peg transfer, inverted peg transfer, and inverted circle cut with each tool and handle angle. Inverted tasks were adapted from standard FLS tasks to simulate advanced tasks observed during abdominal wall surgeries, e.g., ventral hernia. Motion tracking, video analysis, and modified NASA-TLX workload questionnaires were used to measure postures, performance (e.g., completion time and errors), and workload. RESULTS: Task performance did not differ between tools. For FLS peg transfer, self-reported physical workload was lower for B than for A70, and mean wrist postures showed significantly higher flexion for in-line than for pistol grip tools (B and A70). For inverted peg transfer, workload was higher for all configurations. However, less time was spent in at-risk wrist postures for in line (47 %) than for pistol-grip (93-94 %), and most participants preferred Tool A. For inverted circle cut, workload did not vary across configurations, mean wrist posture was 10 degrees closer to neutral for A0 than B, and median time in at-risk wrist postures was significantly less for A0 (43 %) than for B (87 %). CONCLUSION: The best ergonomic wrist positions for FLS (floor) tasks are provided by pistol-grip tools and for tasks on the abdominal wall (ventral surface) by in line handles. Adjustable handle angle laparoscopic tools can reduce ergonomic risks of musculoskeletal strain and allow versatility for tasks alternating between the floor and ceiling positions in a surgical trainer without impacting performance. PMID- 26541722 TI - Resident participation in laparoscopic Roux-en-Y gastric bypass: a comparison of outcomes from the ACS-NSQIP database. AB - BACKGROUND: As clinical outcome data are increasingly tied to hospital reimbursement, balancing quality care with training of surgical residents has become critical. We used the ACS-NSQIP database to determine impact of resident participation in laparoscopic gastric bypass on 30-day morbidity and mortality. METHODS: We queried the ACS-NSQIP database from 1/2005 to 12/2012 for laparoscopic gastric bypass, dividing cases between those with or without resident involvement. Univariate and multivariate analyses of intraoperative and postoperative outcomes were assessed. A sub-analysis was performed to address whether different resident training levels affected outcomes. RESULTS: A total of 43,477 laparoscopic gastric bypass cases were available for analysis; 22,189 had resident involvement (resident = R), and 21,288 did not (no resident = NR). Preoperative characteristics were similar between groups. On multivariate analysis, procedures with resident assistance had increased risk of the following complications: superficial site infection (R = 2.1 vs. 1.5 %, p < 0.001), renal failure (R = 0.4 vs. NR = 0.3 %, p = 0.002), urinary tract infection (R = 1.1 vs. 0.9 %, p = 0.027), and sepsis (R = 0.8 vs. NR = 0.6 %, p = 0.019). Increased operative time in the resident group (29 min, p < 0.0001) demonstrated direct linear association with resident trainee level. There was no statistical difference in the incidences of the following: pulmonary embolism, deep venous thrombosis, deep surgical site infection, organ space infection, pneumonia, unplanned intubation, mechanical ventilation >48 h, septic shock, cardiac arrest, return to the operating room, or mortality. CONCLUSION: Resident participation in laparoscopic gastric bypass was associated with statistically significant, but clinically insignificant increase in incidence of superficial site infection, renal failure, readmission rate, and length of stay. Therefore, although resident participation in laparoscopic gastric bypass is associated with significantly increased operative time, it does not lead to increased mortality and has no clinically significant effect on morbidity. PMID- 26541723 TI - Incisional and port-site hernias following robotic colorectal surgery. AB - BACKGROUND: The association between extraction site location, robotic trocar size, and the incidence of incisional hernias in robotic colorectal surgery remain unclear. Laparoscopic literature reports variable rates of incisional hernias versus open surgery, and variable rates of trocar site hernias. However, conclusions from these studies are confusing due to heterogeneity in closure techniques and may not be generalized to robotic cases. This study evaluates the effect of extraction site location on incisional hernia rates, as well as trocar hernia rates in robotic colorectal surgery. MATERIALS AND METHODS: A retrospective review of multiport and single incision robotic colorectal surgeries from a single institution was performed. Patients underwent subtotal, segmental, or proctocolectomies, and were compared based on the extraction site through either a muscle-splitting (MS) or midline (ML) incision. Hernias were identified by imaging and/or physical exam. Demographics and risk factors for hernias were assessed. Groups were compared using a multivariate logistic regression analysis. RESULTS: The study included 259 colorectal surgery patients comprising 146 with MS and 113 with ML extraction sites. Postoperative computed tomograms were performed on 155 patients (59.8 %) with a mean follow-up of 16.5 months. The overall incisional hernia rate was 5.8 %. A significantly higher hernia rate was found among the ML group compared to the MS group (12.4 vs. 0.68 %, p < 0.0001). Of the known risk factors assessed, only increased BMI was associated with incisional hernias (OR 1.18). No trocar site hernias were found. CONCLUSION: Midline extraction sites are associated with a significantly increased rate of incisional hernias compared to muscle-splitting extraction sites. There is little evidence to recommend fascia closure of 8-mm trocar sites. PMID- 26541724 TI - Randomized controlled trial comparing laparoscopic greater curvature plication versus laparoscopic sleeve gastrectomy. AB - BACKGROUND: Laparoscopic greater curvature plication (LGCP) is a new restrictive bariatric procedure, which has a similar restrictive mechanism like laparoscopic sleeve gastrectomy (LSG) without potential risk of leak. Aim of the study was to compare 2-year outcomes of LSG and LGCP. METHODS: Multicenter prospective randomized trial was started in 2010. A total of 54 patients with morbid obesity were allocated either to LGCP group (n = 25) or LSG group (n = 27). Main exclusion criteria were: ASA > III, age > 75 and BMI > 65 kg/m(2). There were 40 women and 12 men, and the mean age was 42.6 +/- 6.8 years (range 35-62). Data on the operation time, complications, hospital stay, body mass index loss, percentage of excess weight loss (%EWL), loss of appetite and improvement in comorbidities were collected during the follow-up examinations. RESULTS: All procedures were completed laparoscopically. The mean operative time was 92.0 +/- 15 min for LSG and 73 +/- 19 min for LGCP (p > 0.05). The mean hospital stay was 4.0 +/- 1.9 days in the LSG group and 3.8 +/- 1.7 days in LGCP group (p > 0.05). One year after surgery, the mean %EWL was 59.5 +/- 15.4 % in LSG group and 45.8 +/- 17 % in LGCP group (p > 0.05). After 2 years, mean %EWL was 78.9 +/- 20 % in the LSG group and 42.4 +/- 18 % in the LGCP group (p < 0.01). After 3 years, mean %EWL was 72.8 +/- 22 in the LSG group and only 20.5 +/- 23.9 in the LGCP group (p < 0.01). Loss of feeling of hunger after 2 years was 25 % in LGCP group and 76.9 % in the LSG group (p < 0.05). The comorbidities including diabetes, sleep apnea and hypertension were markedly improved in the both groups after surgery. CONCLUSION: The short-term outcomes demonstrated equal effectiveness of the both procedures, but 2-year follow-up showed that LGCP is worse than LSG as a restrictive procedure for weight loss. PMID- 26541725 TI - Multidisciplinary treatment of T1a adenocarcinoma in Barrett's esophagus: contemporary comparison of endoscopic and surgical treatment in physiologically fit patients. AB - BACKGROUND: Previous reports comparing endoscopic therapy (ET) and surgical therapy (ST) have predominantly assessed patients with high-grade dysplasia. The study aim was to compare ET to ST in physiologically fit patients with cT1a adenocarcinoma (EAC). METHODS: Review of two prospective databases yielded 100 patients presenting with clinical cT1a EAC between 2000 and 2013. Only physiologically fit patients who were candidates for either treatment were analyzed. RESULTS: Presenting patient characteristics were similar between ET (n = 36) and ST groups (n = 49). Surgical patients were less likely to be staged with EMR (43 vs 100 %) and were associated with mass lesions >1 cm at EGD (p = 0.01), multifocal EAC (p = 0.03), and positive margins for EAC on EMR (p < 0.05). On multivariate analysis, only multifocal HGD was an independent factor for surgery. Following esophagectomy, R0 resection rates for Barrett's esophagus and cancer were 100 %. Incidence of surgery decreased over the study period from 85 to 25 %. All ET patients had EMR, and 28 patients underwent additional ablative therapies for Barrett's esophagus. Following ET, eradication rates of EAC, dysplasia, and BE were 92, 81, and 53 %, respectively. Morbidity rates were comparable between groups (ST 51 % vs ET 39 %, p = 0.31). In-hospital mortality rate was zero in each group. Recurrence rates in ST and ET group were 2 and 11 % (p = 0.08). In the ET group, two patients with endoluminal cancer recurrence after complete eradication underwent esophagectomy. Age-adjusted overall survival was comparable. CONCLUSION: In high-volume esophageal centers, ST and ET provide equally safe and effective treatment for cT1a EAC in medically fit patients. While the results of this study provide a historical perspective and clearly demonstrate an evolution toward ET over time, the appropriate treatment modality is best selected in a multidisciplinary fashion with EMR providing the most accurate staging. In endoscopically treated patients, indefinite endoscopic follow-up required, however, standardized long-term follow-up protocols are needed. PMID- 26541726 TI - Sutureless onlay hernia repair: a review of 97 patients. AB - BACKGROUND: Repair of large ventral/incisional (V/I) hernias is a common problem. Outside of recurrence, other factors such as wound complications and mesh infection can create significant morbidity. Chevrel described the premuscular repair and later modified it by using glue over the midline closure. We previously described our onlay technique using fibrin glue alone in a small case series. The aim of this study is to review the largest case series of sutureless onlay V/I hernia repair whereby mesh is fixated with fibrin glue alone for complex ventral hernias, and how the technique has evolved. METHODS: All patients who underwent onlay V/I hernia repair over a 3-year period were reviewed. Patient demographics, operative details, complications, and follow-up were reviewed. RESULTS: In total, 97 patients were included. 54.6 % were female, with a mean age of 57.3 years. Mean BMI was 32.2. 23(23.7 %) patients had diabetes. 90 (92.8 %) of the operations were for incisional hernias, 3 (3.1 %) primary ventral hernias, 2 (2.1 %) flank hernias, and 2 (2 %) complex abdominal wall reconstruction. 88 (90.7 %) of the cases were performed on an elective basis. 77 (77.3 %) cases were classified as clean, 21 (21.6 %) clean-contaminated, and 1 (1.0 %) contaminated. The mean defect size was 150 cm(2). Mean follow-up was 386 days, and maximum was 3.1 years. There were 21 (21.6 %) seromas, 4 (4.1 %) wound infections, 7 (7.4 %) had skin necrosis, and 9 (9.3 %) required re-operation due to a complication. At 3 years, there have been no recurrences or mesh explants. CONCLUSIONS: The sutureless onlay V/I hernia repair with fibrin glue fixation has proven to be durable with a comparable complication profile to other techniques. The most common sequela, seroma, is easily managed in the outpatient setting. This sutureless technique is an effective option for onlay hernia repair that may provide several advantages over traditional suture techniques. PMID- 26541727 TI - Safety and efficacy of 1020 consecutive laparoscopic sleeve gastrectomies performed as a primary treatment modality for morbid obesity. A single-center experience from the metabolic and bariatric surgical accreditation quality and improvement program. AB - BACKGROUND: LSG is widely accepted as a definitive treatment for obesity. Due to lack of large series with long-term follow-up, disagreement remains regarding its safety and efficacy. We present a series of 1020 consecutive LSGs performed with long-term follow-up. METHODS: A retrospective review of a prospectively collected database was conducted on patients who underwent LSG from January 2005 to February 2014. Data included weight, height, BMI, ideal body weight, comorbid conditions, intraoperative complications, mean length of hospital stay (LOS), early (<30 days) readmission, early and late (>30 days) postoperative complications, and percentage of excess weight loss (%EWL). RESULTS: Of the 1020 patients, 66.6 % (n = 679) were female, with a mean age of 38.4 +/- 16.5 years. Mean BMI at the time of first visit was 43.4 +/- 5.8 kg/m(2). The most common comorbid conditions identified were diabetes mellitus (89.4 %), sleep apnea (86.4 %), hypertension (80.3 %), and hyperlipidemia (70 %). Over the entire follow-up period, 57 % of diabetic patients experienced significant improvement or remission. There was no mortality in this series. Early postoperative complications within 30 days of surgery included leak in 0.1 % (n = 1), stricture in 0.1 % (n = 1), emesis in 23 % (n = 234), dehydration in 19 % (n = 194), prolonged ileus in 18 % (183), and self-limited bleeding in 3 % (n = 30). Mean LOS was of 3.4 +/- 2.1 days, with a 3.8 % overall rate of early readmissions. Long-term morbidity was found in 3.9 % of patients (n = 40) and included stricture in 0.49 % (n = 5) and GERD in 6 % (n = 61). The overall 30-day mortality rate was 0 %. Mean %EWL at 3 months to 1, 3, 5, and 8 years was 72 +/- 16.8, 86 +/- 22.3, 63 +/- 19, 61 +/- 11, and 52 +/- 9.2, respectively. CONCLUSIONS: This study confirms that LSG is safe and has very low rates of early and long-term complications when compared to other well-established procedures. Additionally, LSG that appears results in significant improvement of obesity related comorbid conditions. PMID- 26541728 TI - A multicenter study of initial experience with single-incision robotic cholecystectomies (SIRC) demonstrating a high success rate in 465 cases. AB - BACKGROUND: Recently, the robotic single-site platform has been used to ameliorate the difficulties seen in single-incision laparoscopic surgery (SILC) while preserving the benefits of standard laparoscopic cholecystectomy. The purpose of this study is to describe the clinical outcomes of a large series of single-incision robotic cholecystectomy (SIRC). METHODS: Medical records of consecutive patients who underwent SIRC were retrospectively reviewed. All procedures were performed by six surgeons at five different North American centers involved in the study. All patients included in the study underwent a cholecystectomy attempted through single site at the umbilicus, using the da Vinci((r)) Surgical System (Intuitive Surgical Inc. Sunnyvale, CA). RESULTS: A total of 465 patients met study criteria. Median age was 48 years (range 18-89); 351 (75.5 %) were female and 304 (66.4 %) were overweight or obese. Except for gender, case characteristics differed significantly by surgeon/site. Previous abdominal surgery was reported for 226 (48.6 %) cases. SIRC was successfully completed in 455 (97.8 %) cases, and there were no conversions to open surgery. Median surgical time was 52 min with a decreasing trend after 55-85 cases. Male gender, obesity and diagnoses other than biliary dyskinesia were independent predictors of longer surgical times. The complication rate was 2.6 %. CONCLUSIONS: Our large, multicenter study demonstrates that robotic single-site cholecystectomy is safe and feasible in a wide range of patients. PMID- 26541729 TI - Quality-of-life scores in laparoscopic preperitoneal inguinal hernia repair. AB - BACKGROUND: Published support exists for using lightweight polypropylene mesh (PPM) to repair inguinal hernias with increased biocompatibility and decreased foreign body reaction and pain. However, quality of life (QOL) has not been assessed. We assess QOL in patients undergoing laparoscopic totally extraperitoneal hernia repair (TEP) with lightweight PPM. METHODS: We performed an IRB-approved study of patients undergoing TEP hernia repair. Demographic information and hernia characteristics were collected perioperatively. Baseline Short Form-36 (SF-36), Carolinas Comfort Scale (CCS), and visual analog scale (VAS) for pain were performed preoperatively, and then after 1, 26, and 52 weeks. RESULTS: Forty-eight patients undergoing TEP with mesh were selected. Average age was 43.2 years (SD = 13.2), and average BMI was 26.1 kg/m(2) (SD = 4.3). Procedures include bilateral hernia, right inguinal hernia, and left inguinal hernia repairs. Mean scores on the CCS((r)) and VAS were low during the immediate post-op period and 1 year. SF-36 mean scores for body pain, physical function, and role physical showed decreases at the postoperative survey and then subsequent increases. Pain-associated scores increased during the immediate post op period. CCS and SF-36 scores demonstrated improvement after 1 year. There was no significant difference in VAS. Bilateral repair patients reported more pain and reduced physical function versus unilateral repairs. Patients with larger mesh reported greater pain scores and reduced physical function scores. CONCLUSIONS: Laparoscopic inguinal hernia repair is associated with initial declines in QOL in the postoperative period. Improvements appear in the long term. General health does not appear to be impacted by laparoscopic TEP. Smaller mesh and unilateral repairs are associated with improved QOL following laparoscopic TEP with PPM. Multiple metrics for QOL are required to reflect patient recovery. PMID- 26541730 TI - Charges, outcomes, and complications: a comparison of magnetic sphincter augmentation versus laparoscopic Nissen fundoplication for the treatment of GERD. AB - BACKGROUND: Magnetic sphincter augmentation (MSA) is approved for uncomplicated GERD. Multiple studies have shown MSA to compare favorably to laparoscopic Nissen fundoplication (LNF) in terms of symptom control with results out to 5 years. The MSA device itself, however, is an added cost to an anti-reflux surgery, and direct cost comparison studies have not been done between MSA and LNF. The aim of the study was to compare charges, complications, and outcome of MSA versus LNF at 1 year. METHODS: This is a retrospective analysis of all patients who underwent MSA or LNF for the treatment of GERD between January 2010 and June 2013. Patient charges were collected for the surgical admission. We also collected data on 30 day complications and symptom control at 1 year assessed by GERD-HRQL score and PPI use. RESULTS: There were 119 patients included in the study, 52 MSA and 67 LNF. There was no significant difference between the mean charges for MSA and LNF ($48,491 vs. $50,111, p = 0.506). There were significant differences in OR time (66 min MSA vs. 82 min LNF, p < 0.01) and LOS (17 h MSA vs. 38 h LNF, p < 0.01). At 1-year follow-up, mean GERD-HRQL was 4.3 for MSA versus 5.1 for LNF (p = 0.47) and 85 % of MSA patients versus 92 % of LNF patients were free from PPIs (p = 0.37). MSA patients reported less gas bloat symptoms (23 vs. 53 %, p <= 0.01) and inability to belch (10 vs. 36 %, p <= 0.01) and vomit (4 vs. 19 %, p <= 0.01). CONCLUSION: The side effect profile of MSA is better than LNF as evidenced by less gas bloat and increase ability to belch and vomit. LNF and MSA are comparable in symptom control, safety, and overall hospital charges. The charge for the MSA device is offset by less charges in other categories as a result of the shorter operative time and LOS. PMID- 26541731 TI - Knotless choledochorraphy with barbed suture, safe and feasible. AB - PURPOSE: To describe the safety and feasibility of a running continuous unidirectional barbed suture (V-Loc, Covidien, Mansfield, MA) for primary common bile duct closure while performing laparoscopic common bile duct exploration (LCBDE). INTRODUCTION: LCBDE is nowadays the best approach for treating complex common bile duct lithiasis or cases where the endoscopic retrograde cholangiopancreatography has failed. It is clear that the primary closure of the common bile duct must be preferred over the T-tube drainage. The actual technical aspects offer room for improvement. We present our experience with barbed suture, for which recently, various fields of surgery have become interested in and which now has a series of studies that support it for several uses. METHODS: Between July 2012 and July 2014, 54 consecutive patients with bile duct stones underwent LCBDE by a single surgeon. Perioperative outcomes and 30-day complications were recorded. RESULTS: Upon the completion of the exploration, 50 patients had primary common bile duct closure using knotless unidirectional barbed 3-0 V-Loc 90 suture, and 4 patients were excluded. All of the sutures were performed without knot tying. The procedure in all patients was successfully performed with no intraoperative complications. There were no bile leaks in the 50 patients or other postoperative complications such as infection, need for reintervention or death. CONCLUSION: The use of unidirectional knotless barbed suture (V-Loc 90) is safe, feasible and effective on LCBDE for primary common bile duct closure. The biliary leak rate is acceptably low and comparable to the rate reported in the literature. This report is our initial experience that needs further clinical trials. PMID- 26541732 TI - Is there anything we can modify among factors associated with morbidity following elective laparoscopic sigmoidectomy for diverticulitis? AB - BACKGROUND: Laparoscopic sigmoidectomy for diverticulitis is widely accepted, using either endolinear staplers or traditional linear staplers under direct vision through the extraction site to transect the rectum. The aim of this study was to assess modifiable factors affecting perioperative morbidity after elective laparoscopic sigmoidectomy for diverticulitis. METHODS: Potential associations between perioperative morbidity and demographic, disease-related, and treatment related factors were assessed on all consecutive patients included in a prospectively collected database undergoing elective laparoscopic sigmoidectomy for diverticulitis between 1992 and 2013. Rectal transection with a linear stapler under direct vision through the extraction site was considered compatible with laparoscopic technique. RESULTS: There were two deaths out of 1059 patients (0.19 %). Conversion rate was 13.1 %, overall morbidity 28 %, and anastomotic leak 3.7 %. Independent factors associated with morbidity in an intent-to-treat analysis were ASA 3 (OR 1.53, p = 0.006), conversion (OR 1.71, p = 0.015), and rectal transection without endolinear stapling (traditional linear stapler: OR 1.75, p = 0.003; surgical knife: OR 2.09, p = 0.002). The same factors along with complicated diverticulitis (OR 1.56, p = 0.013) were independently associated with overall morbidity among laparoscopically completed cases. BMI >= 35 (OR 2.3, p = 0.017), complicated diverticulitis (OR 2.37, p = 0.002), and rectal transection with a traditional linear stapler (OR 2.19, p = 0.018) were independently associated with abdomino-pelvic infections, both in an intent-to treat analysis and among laparoscopically completed cases. The number of endolinear stapler firings was not associated with morbidity. CONCLUSIONS: Most factors associated with morbidity of laparoscopic sigmoidectomy for diverticulitis cannot be easily modified. With the limitation of a retrospective analysis, modifiable factors to minimize morbidity are laparoscopic completion and endolinear stapling. PMID- 26541733 TI - Is laparoscopic repair of incarcerated abdominal hernias safe? Analysis of short term outcomes. AB - BACKGROUND: There is a paucity of literature surrounding the safety and feasibility of laparoscopic repair for acutely incarcerated abdominal hernias. The objective of this study was to compare the 30-day morbidity and mortality between laparoscopic and open repairs of incarcerated abdominal hernias. METHODS: A retrospective cohort study was conducted using data from the National Surgery Quality Improvement Program from 2005 to 2012. The study population was selected using ICD-9 diagnostic codes describing abdominal hernias with obstruction, but without gangrene. Cases with documented bowel resection were excluded. Group classification was based on CPT coding. Study outcomes included the 30-day major complication, reoperation and mortality rates. Multivariable logistic regression models were used to adjust for confounding for all study outcomes. RESULTS: A total of 2688 and 15,562 patients were in the laparoscopic and open group, respectively. After adjustment for clinically relevant confounders, laparoscopic surgery was associated with a significantly lower 30-day infectious (OR 0.36, p < 0.001, 95 % CI 0.23-0.56) and serious complication rates (OR 0.66, p < 0.001, 95 % CI 0.55-0.80). However, there was no statistical difference with respect to the 30-day reoperation (OR 0.81, p = 0.28, 95 % CI 0.56-1.18) or mortality rates (OR 0.94, p = 0.80, 95 % CI 0.58-1.53). CONCLUSIONS: Patients with incarcerated abdominal hernias who underwent laparoscopic repair had a significantly lower 30 day morbidity compared to patients with open repair. Although the 30-day reoperation and mortality rates were also lower, there was no statistically significant difference. Laparoscopic surgery appears to be safe in the management of select incarcerated abdominal hernias. PMID- 26541734 TI - Prospective evaluation of a simplified narrowband imaging scoring system for a differential diagnosis of colorectal lesions. AB - BACKGROUND: Narrowband imaging (NBI) allows characterization of colorectal polyps during endoscopy; however, this is underutilized by most US physicians. The aim of this study was to assess diagnostic performance of an NBI scoring system, based on the NBI international colorectal endoscopic classification, and determine a threshold score yielding the highest negative predictive value (NPV) in the characterization of colorectal neoplasia. METHODS: During colonoscopy, colorectal lesions were scored using the NBI scoring system on a 0-3 scale for NBI findings. All lesions were biopsied or endoscopically removed for pathological examinations. RESULTS: Two hundred and three patients were enrolled, and a total of 156 colorectal lesions were detected in 67 patients. Diagnostic yields under white light mode showed limited diagnostic performance [accuracy 75.6 % (68.9-82.3), sensitivity 69.2 % (58.6-78.3), specificity 84.6 % (73.1 92.0), positive predictive value (PPV) 86.3 % (75.8-92.9), NPV 66.3 % (55.0 76.0)]. Of NBI threshold scores from 1 to 3 for the diagnosis of neoplastic lesion, the score of >=1 resulted in an accuracy of 88.5 % (83.5-93.5), sensitivity of 97.8 % (91.5-96.6), and specificity of 75.4 % (62.9-84.9), with PPV of 84.8 % (76.1-90.8) and NPV of 96.1 % (85.4-99.3). CONCLUSIONS: The threshold value of >=1 in this simplified NBI scoring system yielded the highest sensitivity and NPV for non-adenomatous colorectal polyps. This scoring system is simple to apply and is superior to white light endoscopy. PMID- 26541735 TI - Trends in colorectal cancer admissions and stage at presentation: impact of screening. AB - BACKGROUND: Colorectal cancer (CRC) incidence is rising among patients under age 50. As such, we set out to determine the proportion of CRC-related hospital admissions and distribution of colon cancer by stage in different age groups. METHODS: The NIS database for 2002-2012 was used to investigate trends of colorectal cancer resection by age, and the ACS NSQIP database for 2012-2013 was used to investigate contemporary stage at diagnosis for colon cancer in different age groups. RESULTS: A total of 1,198,421 patients were admitted to a hospital with a diagnosis of CRC and captured by the NIS database. Although the number of hospitalized CRC patients decreased from 2002 to 2012, the observed decrease was predominant in patients older than 65 years (P < 0.01) and in colon cancer compared to rectal cancer patients (P < 0.01). The proportion of patients younger than 65 years increased from 32.8 % in 2002 to 41.1 % in 2012, and the proportion of patients under age 50 increased from 9 to 12 %. In the NSQIP database, the age <50 group also had a significantly higher proportion of advanced disease (stage III/IV) compared to patients age 50 and older (62.3 vs. 47.5 %, P < 0.01). In 2012, it was observed that most patients with rectal cancer were younger than 65 years (55.8 %). CONCLUSION: There was a steady decrease in the number of hospitalized patients with colorectal cancer during the last decade, primarily attributable to a decrease in the older than 65 years age patients and colon cancer patients. The proportion of hospitalized patients age <50 is rising. In addition, patients younger than 50 years were more likely to have advanced disease compared to older patients. PMID- 26541736 TI - Comparison of the cost and outcomes following totally laparoscopic and laparoscopy-assisted distal gastrectomies for gastric cancer: a single institution comparison. AB - OBJECTIVE: This study aimed to compare the short-term surgical outcomes and cost benefits following totally laparoscopic distal gastrectomy (TLDG) and laparoscopy assisted distal gastrectomy (LADG) for the treatment of gastric cancer. METHODS: Between April 2007 and December 2013, a total of 100 patients with gastric cancer underwent laparoscopic distal gastrectomy. The patients were classified into two groups according to whether intracorporeal anastomosis or extracorporeal anastomosis had been performed. The comparison between the groups was based on clinicopathological characteristics and surgical and economic outcomes. RESULTS: There were 57 and 43 patients who underwent TLDG and LADG, respectively. The patients' demographics and tumor characteristics did not show any statistically significant differences with the exception for tumor location. In the LADG group, tumors were localized to relatively higher positions (p = 0.024) and received Roux-en-Y reconstruction more frequently (p < 0.001). There were no differences in the incidence of morbidity. Anastomotic leakage was not recorded in either group, although anastomotic stenosis occurred in one patient (1.8 %) after TLDG and in two patients (4.7 %) after LADG. Compared with the LADG group, the TLDG group was associated with significantly less operative blood loss (p < 0.001), a shorter time to oral intake (p = 0.012), and hospital stay (p = 0.018). The median operation costs were greater in the TLDG group than in the LADG group (Y982,000 in TLDG vs. Y879,830 in LADG; p < 0.001), whereas the median total hospital costs were similar between the two groups (Y1302,665 in LADG vs. Y1383,322 in TLDG: p = 0.119). CONCLUSION: This study suggests that TLDG is as technically feasible, safe, and effective as LADG for treating patients with gastric cancer. Furthermore, TLDG is associated with equivalent total hospital costs compared with LADG. The increased operation cost is offset by the decreased costs associated with longer periods of hospitalization. PMID- 26541737 TI - Laparoscopic sigmoid colectomy: Are all laparoscopic techniques created equal? AB - BACKGROUND: Laparoscopic colectomy has been associated with improved postoperative pain control, earlier return to work, and shorter hospital stays compared to open colectomy. However, there are varied technical approaches to laparoscopic resections. We therefore sought to determine whether the straight laparoscopic approach was associated with shorter length of stay compared to hand assisted and laparoscopic-assisted techniques for sigmoid colectomies. METHODS: A retrospective review of laparoscopic sigmoid colectomies performed by five colorectal surgeons from 2010 to 2014 was performed. Approaches were defined as: (1) straight laparoscopic if colon mobilization, inferior mesenteric artery transection and intra-corporeal anastomosis were performed laparoscopically, (2) hand assisted if a hand port was utilized to assist with mobilization and vessel transection, and (3) laparoscopic assisted if only the colon mobilization was performed intra-corporeally. Poisson regression was performed to determine the impact of surgical technique on LOS while controlling for differences in patient factors. RESULTS: A total of 191 patients were identified with 71 straight laparoscopic, 57 hand-assisted, and 63 laparoscopic-assisted cases. Substantial variability in choice of surgical technique was seen across surgeons. Patient populations were similar, with the exception of hand-assisted procedures being more often used in obese patients. Unadjusted average postoperative days to discharge were 3.6 days for straight laparoscopic and 4.1 and 4.0 days for hand assisted and laparoscopic-assisted approaches, respectively. While controlling for factors associated with longer hospital stay, the straight laparoscopic approach was associated with a 14 % shorter stay compared to laparoscopic assisted colectomy and a 15 % shorter stay compared to hand-assisted colectomy. The straight laparoscopic approach was also associated with earlier return of bowel function compared to other approaches. CONCLUSIONS: The straight laparoscopic approach to sigmoid colectomy is associated with substantially shorter postoperative stay and earlier return of bowel function when compared to hand-assisted and laparoscopic-assisted techniques. When technically feasible, the straight laparoscopic approach is preferred. PMID- 26541738 TI - Dexmedetomidine versus morphine infusion following laparoscopic bariatric surgery: effect on supplemental narcotic requirement during the first 24 h. AB - INTRODUCTION: The primary aim of this pilot study was to determine whether the dexmedetomidine infusion initiated immediately after laparoscopic bariatric surgery, offers an advantage over a morphine infusion with respect to rescue morphine and paracetamol requirements over the first 24 post-operative hours. METHODS: Sixty morbidly obese adult patients scheduled for laparoscopic bariatric surgery were randomly assigned to receive an infusion of either 0.3 mcg/kg/h dexmedetomidine (Group D) or 3 mg/h Morphine (Group M) for 24 h immediately post operatively. All patients received standardized general anesthesia and were evaluated and treated for pain in the intensive care unit by providers who were blinded to their treatment group. The primary outcome was the need for supplemental, "rescue" paracetamol (Dolargan. Hikma, Jordan) and morphine titrated to achieve visual analog scales (VAS) of <40 and <70, respectively. RESULTS: A total of 60 patients (77 % female, mean age 33.5 years +/- 9.5 and body mass index (BMI) 43.0 +/- 4.5) were randomized to Group M and 30 to Group D. There were no significant differences in mean rescue paracetamol and morphine requirements. Mean total morphine requirements in Group D were 6.1 +/- 3.1 mg, whereas 72.9 +/- 2.2 mg in Group M (p < 0.0001). CONCLUSIONS: An intravenous infusion of dexmedetomidine, initiated and continued for 24 h following laparoscopic bariatric surgery, can decrease the overall morphine requirements during this period. This pilot study demonstrated that the post-operative initiation of dexmedetomidine can be morphine sparing following laparoscopic bariatric surgery. PMID- 26541739 TI - Applicability of laparoscopic approach to the resection of large adrenal tumours: a retrospective cohort study on 200 patients. AB - BACKGROUND: Controversies exist in the best surgical approach (open vs. laparoscopy) to large adrenal tumours without peri-operative evidence of primary carcinoma, mainly due to possible capsular disruption of an unsuspected malignancy. In addition, intra-operative blood loss, conversion rate, operative time, and hospital stay may be increased with laparoscopy. THE AIMS OF OUR STUDY WERE: (1) to compare clinical outcomes of laparoscopic adrenalectomy for large versus small adrenal tumours and (2) to identify risk factors associated with increased operative time and hospital stay in laparoscopic adrenalectomy. METHODS: This is a multicentre retrospective cohort study in a large patient population (N = 200) who underwent laparoscopic adrenalectomy in 2004-2014 at three Italian academic hospitals. Patients were divided into two cohorts according to tumour size: "large" tumours were defined as >=5 cm (N = 50) and "small" tumours as <5 cm (N = 150). Further analysis adopting a >=8 cm (N = 15) cut-off size was performed. RESULTS: The study groups were comparable in age and gender distribution as well as their tumour characteristics. The operative time (p = 0.671), conversion rate (p = 0.488), intra- (p = 0.876) and post-operative (p = 0.639) complications, and hospital stay (p = 0.229) were similar between groups. With a cut-off size >=5 cm, the early study period (2004-2009), which included operators' learning curve, was associated with increased risk of longer operative time (HR 0.57; 95 % CI 0.40-0.82), while American Society of Anaesthesiology score >=3 was associated with prolonged hospital stay (HR 0.67; 95 % CI 0.47-0.97). Tumour size >=8 cm was associated with prolonged operative time (HR 0.47; 95 % CI 0.24-0.94). CONCLUSIONS: Surgeons skilled in advanced laparoscopy and adrenal surgery can perform laparoscopic adrenalectomy safely in patients with >=5-cm tumours with no increase in hospital stay, or conversion rate, although operative time may be increased for >=8-cm tumours. Surgeon' experience, size >=8 cm, and patient comorbidities have the largest impact on operative time and length of hospital stay in laparoscopic large adrenal tumour resection. PMID- 26541740 TI - Multi-institutional outcomes using magnetic sphincter augmentation versus Nissen fundoplication for chronic gastroesophageal reflux disease. AB - BACKGROUND: Magnetic sphincter augmentation (MSA) has emerged as an alternative surgical treatment of gastroesophageal reflux disease (GERD). The safety and efficacy of MSA has been previously demonstrated, although adequate comparison to Nissen fundoplication (NF) is lacking, and required to validate the role of MSA in GERD management. METHODS: A multi-institutional retrospective cohort study of patients with GERD undergoing either MSA or NF. Comparisons were made at 1 year for the overall group and for a propensity-matched group. RESULTS: A total of 415 patients (201 MSA and 214 NF) underwent surgery. The groups were similar in age, gender, and GERD-HRQL scores but significantly different in preoperative obesity (32 vs. 40 %), dysphagia (27 vs. 39 %), DeMeester scores (34 vs. 39), presence of microscopic Barrett's (18 vs. 31 %) and hiatal hernia (55 vs. 69 %). At a minimum of 1-year follow-up, 354 patients (169 MSA and 185 NF) had significant improvement in GERD-HRQL scores (pre to post: 21-3 and 19-4). MSA patients had greater ability to belch (96 vs. 69 %) and vomit (95 vs. 43 %) with less gas bloat (47 vs. 59 %). Propensity-matched cases showed similar GERD-HRQL scores and the differences in ability to belch or vomit, and gas bloat persisted in favor of MSA. Mild dysphagia was higher for MSA (44 vs. 32 %). Resumption of daily PPIs was higher for MSA (24 vs. 12, p = 0.02) with similar patient-reported satisfaction rates. CONCLUSIONS: MSA for uncomplicated GERD achieves similar improvements in quality of life and symptomatic relief, with fewer side effects, but lower PPI elimination rates when compared to propensity-matched NF cases. In appropriate candidates, MSA is a valid alternative surgical treatment for GERD management. PMID- 26541741 TI - A novel approach of optical biopsy using probe-based confocal laser endomicroscopy for peritoneal metastasis. AB - BACKGROUND: In digestive cancers, it is mandatory to diagnose peritoneal metastasis prior to selecting therapy. Therefore, exploratory laparoscopy has gained wider clinical acceptance. In laparoscopy, the peritoneal metastasis is pathologically confirmed by excisional biopsy; however, there remain technical difficulties in performing precise diagnosis and adequate biopsy on small peritoneal lesions without damaging organs. We have focused on "optical biopsy" using probe-based confocal laser endomicroscopy (pCLE). The aims of this study were (1) to optimize current CLE system for real-time observation of peritoneal metastases and (2) to assess its potential usefulness as diagnostic modality in preclinical settings. METHODS: To optimize condition and evaluate feasibility, we prepared peritoneal metastasis mice model with gastric cancer cell line (MKN-45). On Day 10 after seeding, the mice were laparotomized and performed pCLE observations with CellvizioLAB (LSU-F 400/488 nm, Mauna Kea Technologies, Paris, France). We evaluated two different CLE probes, three different dyes, and optimal interval time. The detected sites were excised and pathologically evaluated on its morphology. Next, the feasibility and safety were validated in porcine model for clinical usage. After injection of fluorescein, pCLE was applied for the observation of intra-abdominal organs. RESULT: A miniature probe-type pCLE system with 60 MUm focal depth (UltraMini O) and 1 % fluorescein dye was chosen for good visualization in mice model. The irregular microarchitecture images suspected to malignancy were obtained from the metastases. In the porcine model, observation of abdominal organs was feasible without any organ injury in the laparoscopic procedures. The dosage of 1 % fluorescein (3 ml/body) was appropriate in observing intra-abdominal organs, and each intra-abdominal organ was clearly observed with the same imaging quality we obtained in mice model. CONCLUSION: The pCLE was feasible and safe and potentially useful for the diagnosis of the peritoneal metastasis in in vivo animal models. PMID- 26541742 TI - Lateral approach liver hanging maneuver in laparoscopic anatomical liver resections. AB - BACKGROUND: The liver hanging maneuver is a novel technique that is widely used in open liver resection. The hanging technique has been rarely applied during laparoscopic liver resection because a blind dissection between the anterior surface of the inferior vena cava and the liver is required. Dissection between the right and middle hepatic vein is necessary in right hepatectomy, as is dissection between the middle and left hepatic vein in left hepatectomy. The aim of this study was to introduce the lateral approach liver hanging maneuver in laparoscopic anatomical liver resections. METHOD: For this technique, the upper end of the hanging tape was placed on the lateral side of the right or left hepatic vein and the lower end of the hanging tape between three Glisson's pedicles. The pathway of the tape was situated along the lateral side of the inferior vena cava in right-sided hepatectomy or the ligamentum venosum in left sided hepatectomy. RESULTS: From February 2013 to October 2014, this technique was performed in 35 patients. Of these patients, ten patients underwent a right hepatectomy, 5 patients underwent a right posterior sectionectomy, 12 patients underwent a left hepatectomy, and 8 patients underwent a left lateral sectionectomy. The median operative time was 240 min (range 90-390 min), and median blood loss was 350 ml (range 60-700 ml). Blood transfusion was required in six patients (17.1 %). In two patients (5.7 %), postoperative complications were observed due to intra-abdominal fluid collection and pneumonia, respectively. No postoperative mortality was encountered. CONCLUSION: The lateral approach liver hanging maneuver is a simple, safe, and reproducible approach as dissection of the anterior surface of the inferior vena cava and between the three major hepatic veins is not required. This technique may be useful in laparoscopic anatomical liver resections. PMID- 26541743 TI - Total laparoscopic resection for advanced gastric cancer is safe and feasible in the Western population. AB - BACKGROUND: There is debate surrounding the use of laparoscopic resection for advanced gastric cancer in the Western population. Here we aim to assess the feasibility and short-term outcomes of laparoscopic gastrectomy in consecutive patients in a Western population. METHODS: From 2012 to 2014, retrospective review of 28 patients with clinically staged advanced gastric cancer (>=T3 or >=N1) treated with laparoscopic resection. RESULTS: Sixty-one percentage of patients were male. Median age was 67 years (range 35-86). Median BMI was 26.5 (range 19.4-46.1). Resection types were proximal (n = 2), distal (n = 14), and total (n = 12). Twenty-six (93 %) patients underwent D2 lymphadenectomy. Four patients underwent conversion to open. Median blood loss was 125 mL (range 30 300). Median LOS was 7 days (range 4-16). Of postoperative complications, five were minor: arrhythmia (n = 1), surgical site infection (n = 3), in-hospital fall (n = 1); and four were major (intra-abdominal abscess, stricture, PE, and anastomotic bleed). T stages were Tx (n = 1), T2 (n = 3), T3 (n = 18), and T4 (n = 6). N stages were N0 (n = 4), N1 (n = 8), N2 (n = 1), and N3 (n = 15). Median tumor size was 5.8 cm (range 0-9.5). Median lymph node yield was 22 (range 6-53). All margins were negative. Median follow-up was 12.8 months (range 2-27). Six patients have died of progressive disease. CONCLUSION: Following total laparoscopic resection for advanced gastric cancer, oncologic endpoints, postoperative course, and early cancer-specific follow-up are excellent. The results demonstrated here support the routine use of these techniques in the Western patient population. PMID- 26541746 TI - Erratum. PMID- 26541747 TI - Regenerative potential of human adipose-derived stromal cells of various origins. AB - In regenerative concepts, the potential of adult stem cells holds great promise concerning an individualized therapeutic approach. These cells provide renewable progenitor cells to replace aged tissue, and play a significant role in tissue repair and regeneration. In this investigation, the characteristics of different types of adipose tissue are analysed systematically with special attention to their proliferation and differentiation potential concerning the angiogenic and osteogenic lineage. Tissue samples from subcutaneous, visceral, and omental fat were processed according to standard procedures. The cells were characterized and cultivated under suitable conditions for osteogenic and angiogenic cell culture. The development of the different cell cultures as well as their differentiation were analysed morphologically and immunohistochemically from cell passages P1 to P12. Harvesting and isolation of multipotent cells from all three tissue types could be performed reproducibly. The cultivation of these cells under osteogenic conditions led to a morphological and immunohistochemical differentiation; mineralization could be detected. The most stable results were observed for the cells of subcutaneous origin. An osteogenic differentiation from adipose-derived cells from all analysed fatty tissues can be achieved easily and reproducibly. In therapeutic concepts including angiogenic regeneration, adipose-derived cells from subcutaneous tissue provide the optimal cellular base. PMID- 26541748 TI - Analysis of the 50 most cited papers in craniofacial surgery. AB - The intent of this study is to discuss the most prominent literature in craniofacial surgery. To do so, using the ISI Web of Science, a ranking by average number of citations per year of the top 50 craniofacial surgery articles was compiled. All plastic surgery journals listed in the "Surgery" category in the ISI Web of Knowledge Journal Citation Reports 2013 Science Edition were considered. Journal of publication, country of origin, collaborating institutions, topic of interest, and level of evidence were analyzed. The total number of citations ranged from 47 to 1017. Average number of citations per year ranged from 46.2 to 8.6. The oldest article in the top 50 was published in 1988 and the most recent in 2009. The majority of the articles came from Plastic and Reconstructive Surgery with 28 of the 50. The majority of the articles, originated from the United States (56%). Reconstruction of acquired defects was the most commonly examined topic at 46.2%; followed by articles discussing reconstruction of congenital defects (23.1%). The most common level of evidence was level 3. This extensive examination of the craniofacial literature highlights the important part that craniofacial surgery takes in the field of plastic surgery. PMID- 26541749 TI - A modified nasoalveolar molding technique for correction of unilateral cleft nose deformity. AB - INTRODUCTION: Traditional Figueroa nasoalveolar molding (NAM) requires weekly or biweekly adjustments to remove acrylic from the palatal plate to narrow the alveolar gap. These frequent adjustments create a burden for patients living far from a hospital. To minimize this burden, we developed a modified NAM technique using simplified lip taping and a passive palatal plate. Herein we present our clinical experience and outcomes using the traditional and modified methods. MATERIAL AND METHODS: In this blinded, retrospective study of 66 patients with complete unilateral cleft lip and palate, 33 received the traditional NAM and 33 received the modified NAM. Pretreatment and posttreatment facial photographs and clinical charts were used to compare efficacy (nostril height ratio, nostril width ratio, columellar angle, nasal base angle), efficiency (molding frequency), incidence of complications (facial irritation, mucosal ulceration), and medical cost. RESULTS: Traditional and modified NAM did not differ in treatment efficacy for nostril height ratio (0.88 +/- 0.14 vs. 0.90 +/- 0.12), nostril width ratio (2.22 +/- 0.39 vs. 2.38 +/- 0.50), columellar angle (73.5 +/- 9.1 degrees vs. 71.3 +/- 11.8 degrees), nasal base angle (5.1 +/- 2.4 degrees vs. 5.9 +/- 2.7 degrees), or alveolar gap width (2.0 +/- 2.0 mm vs. 2.0 +/- 1.7 mm) (all p > 0.05). Traditional NAM was less efficient, i.e., required more adjustments (8.6 +/- 2.0 vs. 6.7 +/- 1.1), and cost more (22016.4 +/- 2012.7 New Taiwan dollars vs. 20137.6 +/- 1173.4 New Taiwan dollars) (both p < 0.001). CONCLUSIONS: Both NAM techniques similarly improved nasal deformities and reduced alveolar gaps, but the modified technique was more efficient and cost less in terms of insurance reimbursement and supplies (labial tapes). PMID- 26541750 TI - Protein cysteine S-nitrosylation inhibits vesicular uptake of neurotransmitters. AB - Previous studies have shown that nitric oxide can induce cysteine S-nitrosylation of total protein in synaptosomes, suggesting that nitric oxide may contribute to the regulation of synaptic protein function. Vesicular neurotransmitter transporters pack neurotransmitters into synaptic vesicles and play an important role in neurotransmission. In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is responsible for the uptake of monoamines, vesicular acetylcholine transporter (VAChT) is responsible for the uptake of acetylcholine, while vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) are responsible for the uptake of glutamate. The purpose of this study was to investigate the role of cysteine S-nitrosylation in the regulation of these vesicular neurotransmitter transporters. Using the biotin switch assay followed by avidin precipitation and immunoblotting we found that the nitric oxide donor nitrosoglutathione (GSNO) not only increased total cysteine S-nitrosylation, but also increased cysteine S-nitrosylation of VMAT2, VAChT, VGLUT1 and VGLUT2 in the mouse brain. Further, GSNO also decreased the vesicular uptake of [(3)H]dopamine, [(3)H]acetylcholine and [(3)H]glutamate. Our studies suggest that the cysteine S nitrosylation may play an important role in the regulation of vesicular neurotransmitter transport. PMID- 26541751 TI - Biobanking of fresh-frozen endoscopic biopsy specimens from esophageal adenocarcinoma. AB - The process of preparing endoscopic esophageal adenocarcinoma samples for next generation DNA/RNA sequencing is poorly described. Therefore, we assessed the feasibility and pitfalls of preparing esophageal adenocarcinoma endoscopic biopsies toward DNA/RNA samples suitable for next-generation sequencing. In this prospective study, four tumor biopsy samples were collected from consecutive esophageal cancer patients during esophagogastroduodenoscopy and fresh-frozen in liquid nitrogen. DNA and RNA were isolated from samples with a tumor percentage of at least 50%. For next-generation sequencing, double-stranded DNA (dsDNA) is required and high-quality RNA preferred. The quantity dsDNA and RNA quantity and quality were assessed with the Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA) and Agilent 2100 Bioanalyzer (Agilent, Santa Clara, CA, USA). Biopsy samples of 69 consecutive patients with esophageal adenocarcinoma were included. In five patients (7%), the tumor percentage was less than 50% in all four biopsies. Using a protocol allowing simultaneous DNA and RNA isolation, the median dsDNA yield was 2.4 MUg (range 0.1-12.0 MUg) and the median RNA yield was 0.5 MUg (range 0.01-2.05 MUg). The median RNA integrity number of samples that were fresh-frozen within 30 minutes after sampling was 6.7 (range 4.2-8.9) compared with 2.5 (1.8-4.5) for samples that were fresh-frozen after 2 hours. The results from this study show that obtaining dsDNA and RNA for next-generation sequencing from endoscopic esophageal adenocarcinoma samples is feasible. Tumor percentage and dsDNA/RNA yield and quality emphasize the need for sampling multiple biopsies and minimizing the delay before fresh-freezing. PMID- 26541745 TI - Hyaluronan as a therapeutic target in human diseases. AB - Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases. PMID- 26541752 TI - Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case-control studies. AB - OBJECTIVE: To quantify the relation between body mass index (BMI) and endometrial cancer risk, and to describe the shape of such a relation. DESIGN: Pooled analysis of three hospital-based case-control studies. SETTING: Italy and Switzerland. POPULATION: A total of 1449 women with endometrial cancer and 3811 controls. METHODS: Multivariate odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression models. The shape of the relation was determined using a class of flexible regression models. MAIN OUTCOME MEASURE: The relation of BMI with endometrial cancer. RESULTS: Compared with women with BMI 18.5 to <25 kg/m(2) , the odds ratio was 5.73 (95% CI 4.28-7.68) for women with a BMI >=35 kg/m(2) . The odds ratios were 1.10 (95% CI 1.09-1.12) and 1.63 (95% CI 1.52-1.75) respectively for an increment of BMI of 1 and 5 units. The relation was stronger in never-users of oral contraceptives (OR 3.35, 95% CI 2.78 4.03, for BMI >=30 versus <25 kg/m(2) ) than in users (OR 1.22, 95% CI 0.56 2.67), and in women with diabetes (OR 8.10, 95% CI 4.10-16.01, for BMI >=30 versus <25 kg/m(2) ) than in those without diabetes (OR 2.95, 95% CI 2.44-3.56). The relation was best fitted by a cubic model, although after the exclusion of the 5% upper and lower tails, it was best fitted by a linear model. CONCLUSIONS: The results of this study confirm a role of elevated BMI in the aetiology of endometrial cancer and suggest that the risk in obese women increases in a cubic nonlinear fashion. The relation was stronger in never-users of oral contraceptives and in women with diabetes. PMID- 26541753 TI - Celiac disease: role of intestinal compartments in the mucosal immune response. AB - Different approaches have been used to study the pattern of cytokines in celiac disease (CD). Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal compartments of CD patients, dissected by LCM, analyzing cytokine expression profile. Frozen section of jejunum was obtained from 15 untreated CD and 15 control. Surface epithelium and lamina propria compartment were isolated by LCM. RNA from each LCM sample was extracted and, after a retrotranscription step, messenger RNA levels for MxA, IL 15, TNF-alpha, IFN-gamma, IL-17alpha, IL-21, IL-10, and TGF-beta were determined by quantitative reverse transcriptase-PCR. Increased gene expression levels of MxA, IL-15, TNF-alpha, IL-10, and TGF-beta was observed in the surface epithelium of untreated CD with respect to control. Furthermore, all the cytokines investigated were upregulated in the lamina propria of untreated CD as compared to control. Within the untreated CD group the expression of IL-15 was higher, in the surface epithelium than in the lamina propria, whereas the expression levels of IL-17 and IL-21 were higher in the lamina propria than in the surface epithelium. Finally, high levels of IL-10 and TGF-beta were detected in both compartments of untreated CD biopsies. In CD, surface epithelium and lamina propria compartments, play a prominent role in determining innate and adaptive immunity, respectively. Conversely, surface epithelium and lamina propria produce high levels of anti-inflammatory cytokines, suggesting that both compartments are involved in the immunoregulatory response. PMID- 26541754 TI - Protective role of carbon dioxide (CO2) in generation of reactive oxygen species. AB - The results testify to the fact that CO2 is a powerful inhibitor of reactive oxygen species (ROS) generation by cells (blood phagocytes and alveolar macrophages of 96 people and cells of inner organs and tissue phagocytes (of liver, brain, myocardium, lungs, kidneys, stomach, and skeleton muscles), as well as by mitochondria of the liver of 186 white mice and human tissues. Generation of ROS was determined using various methods with CO2 directly acting on the cells and bioptates and indirectly on the organism as a whole. CO2 in the concentration of 5.1% (P = 37.5 mmHg), 8.2% (P = 60.0 mmHg), and 20% (P = 146.0 mmHg) in a mixture with air (total pressure = 730 mmHg) inhibits the basal ROS generation by phagocytes on the average by 3.52, 5.69, and 10.03 times, respectively (p < 0.05), and the stimulated by corpuscular particles: (a) zymosan by 3.24, 4.43, and 7.95 times; (b)SiO2: by 2.99, 3.24, and 5.76 times (p < 0.05). This is confirmed by the feet that CO2, along with inhibiting the O2 (-) generation by cells of the various organs, including the liver, as a rule, by 2.19-4.7 times, p < 0.01 or <0.001 induces simultaneously a decrease in the O2 (-) generation by mitochondria isolated from the liver (by 1.91-3.2 times, p < 0.001). The mechanism of CO2 influence is realized, in part, by inhibition of NADPH-oxidase activity. Taken into consideration proven role of CO2 in different pathophysiological conditions, (such as endoarteritis, bronchial asthma, and infectious diseases), present findings may be of clinical interest in terms of potential implementation of CO2 donors as adjuvant therapeutics in these diseases. PMID- 26541755 TI - GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells. AB - GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERalpha), but all the aspects of this regulatory mechanism are not fully explored. This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERalpha, FOXA1, and Cyclin D1. Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1-ERalpha association. Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. PMID- 26541756 TI - Mir-351-5p contributes to the establishment of a pro-inflammatory environment in the H9c2 cell line by repressing PTEN expression. AB - The activated renin-angiotensin-aldosterone system modulates several metabolic pathways that contribute to left ventricular hypertrophy and heart failure. In this metabolic system, angiotensin II modulates heart morphophysiological changes triggered by a series of inflammatory and pro-inflammatory responses; however, the fine tuning associated with the control of this biochemical pathway remains unknown. Here, we investigated elements involved in the post-transcriptional regulation of the pro-inflammatory environment in the H9c2 cardiac cell line, focusing on miRNA elements that modulate PTEN expression. A cellular model of investigation was established and the miR-315-5p was identified as a novel element targeting PTEN in this cardiac cell line, thereby controlling the protein level. This interconnected pathway contributes to the control of the pro inflammatory environment in Ang II-treated cells. PMID- 26541757 TI - Epidemiology of Hirschsprung's Disease in Taiwanese Children: A 13-year Nationwide Population-based Study. AB - BACKGROUND: Hirschsprung's disease (HD) is an important colon disease in children. The aim of this study is to describe the epidemiological features of HD in Taiwanese children. METHODS: We conducted a study from the Taiwan National Health Insurance Research Database and analyzed cases who received surgical intervention between 1998 and 2010 due to HD (International Classification of Diseases, 9(th) Revision, Clinical Modification 751.3) or megacolon (International Classification of Diseases, 9(th) Revision, Clinical Modification 564.7). The incidence, sex ratio, age at the surgical intervention, associated complication, and medical expenditures were analyzed. RESULTS: There were a total of 629 HD cases, including 458 boys and 171 girls, with an overall incidence of 2.2 per 10,000 live births. The male-to-female incidence ratio was 2.38. There was no secular trend of incidence across the years. Seventy-two percent of cases received surgical treatment before the age of 1 year. The younger cases had higher operation-related medical expenditures. Those patients with preoperative enterocolitis (EC) had a higher possibility of postoperative EC than those patients without preoperative EC (34.6% vs. 24.3%, p = 0.013). There were 169 (26.9%) HD cases with additional anomalies, the most common being gastrointestinal and circulatory system anomalies. Of these, 12 (1.9%) cases were Down syndrome. CONCLUSION: The incidence of HD in Taiwanese children, a majority Chinese population, was one per 4545 live births with a male predominance. Preoperative EC was a significant factor that was associated with postoperative EC. The percentage associated with Down syndrome was relatively low, probably due to a prenatal screening program. PMID- 26541759 TI - RETRACTED ARTICLE: The expression of mitochondrial complexes I and III correlates with prognosis or diagnosis in retinoblastoma: immunohistochemical and histopathological parameters. PMID- 26541758 TI - IL-22: a promising candidate to inhibit viral-induced liver disease progression and hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a growing concern all over the world. With the number of patients rising exponentially with each passing day, HCC is a problem that needs immediate attention. Currently, available treatment strategies focus on controlling the damage after the development of HCC. The options available from chemo- and radio-embolization to surgical resection and transplantation are not efficacious as required due to the complex nature of the disease. Liver regeneration and tissue healing are the subject of great interest today. Interleukin-22 (IL-22) is a cytokine with the ability to regenerate and therefore reverse the injuries caused by a wide range of agents. IL-22 acts via STAT molecule and controls the activity of a wide variety of cell survival and proliferation genes. Experimental data has given a positive insight into the role of IL-22 in inhibition of viral and alcohol-induced hepatocellular carcinoma. A further insight into the nature of IL-22 and the factors that can be manipulated in controlling the activity of IL-22 can help to counter the menace caused by the devastating effects of HCC. PMID- 26541760 TI - The increase of circulating PD-L1-expressing CD68(+) macrophage in ovarian cancer. AB - Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease. When expanding the data in peripheral blood, the proportion of PD-L1(+)CD68(+) cell among CD68(+) cells and the intensity of PD-L1 staining on CD68(+) cell in healthy group were similar to that observed in ovarian cyst group; instead, these two measures were significantly higher in ovarian cancer group, thereafter related to TNM stage. Interestingly, intracellular levels of IL-10, IL-6, TNF-alpha, and IFN-gamma in PD-L1(+)CD68(+) macrophage were higher than those in PD-L1(-)CD68(+) macrophage, especially IL-6 expression. Based on the PD-L1 receptor PD-1 expression on tumor infiltrating cytotoxic cells, our data supported that expression of PD-L1 on TAM promoted apoptosis of T cells via interaction with PD-1 on CD8(+)T cells. Taken together, these results suggested that PD-L1-expressing macrophage represents a novel suppressor cell population in ovarian cancer, which contributes immune escape of ovarian cancer. PMID- 26541761 TI - Ambulatory blood pressure monitoring in daily clinical practice - the Spanish ABPM Registry experience. AB - Many patients are hypertensive at the medical settings but show normal blood pressure out of the doctor's office, and are classified as white-coat hypertensives. On the other hand, many patients with controlled hypertension at the clinic show ambulatory blood pressure levels above the thresholds considered for an adequate blood pressure control, known as having masked hypertension. Using data from the Spanish Ambulatory Blood Pressure Monitoring Registry (Spanish ABPM Registry), a national program developed to promote the use of the ambulatory technique for hypertension management in daily practice, we have reviewed the main strengths of this approach, that is the ability to detect discrepancies of blood pressure status with respect to office blood pressure measurement, and to better assess accurate rates of hypertension control. White coat hypertension within patients with elevated office blood pressure, and masked hypertension within office-controlled patients affected one of three patients in each office status. On the other hand, rates of ambulatory blood pressure control (50%) doubled those of office blood pressure control (25%), still remaining half the patients uncontrolled. We think that a systematic use of ambulatory blood pressure monitoring, and strategies to improve blood pressure control constitute key priorities in hypertension management. PMID- 26541762 TI - Staged laryngeal reconstruction with a prefabricated flap for radiation recurrent glottic carcinoma. AB - OBJECTIVES/HYPOTHESIS: Although salvage total laryngectomy remains the definitive approach to recurrent/persistent glottic cancer following failed radiation therapy for favorable early-stage disease, it comes at the price of a permanent laryngostome and an impact on quality of life. We describe a three-stage method of laryngeal reconstruction for salvage partial laryngectomy to address the unique challenges of operating on radiation recurrent/persistent cancer. STUDY DESIGN: This was a single-surgeon retrospective case series of patients who underwent a three-stage laryngeal reconstruction for salvage partial laryngectomy. METHODS: We performed a comprehensive review of the clinical, pathologic, and radiologic files of all patients who underwent a three-stage laryngeal reconstruction for salvage partial laryngectomy. RESULTS: Seven male patients underwent a three-stage laryngeal reconstruction following open partial salvage laryngectomy. The average follow-up time since salvage surgery was 55 months. All patients were without evidence of recurrence and demonstrated satisfactory functional outcomes. CONCLUSION: Staged reconstruction provides a more controlled assessment of wound healing and valuable pathologic information regarding the specific disease virulence and adequacy of the margins. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1061-1070, 2016. PMID- 26541763 TI - Evogliptin: First Global Approval. AB - Evogliptin (Suganon) is an orally bioavailable, selective dipeptidyl peptidase-4 (DPP-4; CD26 antigen) inhibitor being developed by Dong-A ST for the treatment of type 2 diabetes mellitus. DPP-4 inhibitors control glucose levels by preventing the breakdown of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which stimulate insulin secretion in response to the increased levels of glucose in the period following meals. In October 2015, evogliptin received its first global approval in South Korea for blood glucose control in patients with type 2 diabetes mellitus. This article summarizes the milestones in the development of evogliptin leading to this first approval for type 2 diabetes mellitus. PMID- 26541764 TI - Albumin-Bound Paclitaxel: A Review in Non-Small Cell Lung Cancer. AB - Nanoparticle albumin-bound paclitaxel (Abraxane) [hereafter referred to as nab paclitaxel] is a taxane developed to avoid some of the toxicities associated with solvent-bound (sb) paclitaxel. Nab-paclitaxel, in combination with carboplatin, is indicated for the first-line treatment of non-small cell lung cancer (NSCLC) in patients who are not candidates for curative surgery and/or radiation therapy. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of nab-paclitaxel in this indication. Compared with sb-paclitaxel plus carboplatin, nab-paclitaxel plus carboplatin significantly improved the objective response rate (ORR), but did not prolong progression-free survival or overall survival (OS), in the overall population of patients with advanced NSCLC in a multinational phase III trial. The nab-paclitaxel regimen also provided benefit over the sb-paclitaxel regimen in certain patient subgroups, including patients with squamous cell histology (in terms of ORR) and patients who were elderly (in terms of OS). Nab-paclitaxel plus carboplatin had a manageable tolerability profile with some benefits over sb-paclitaxel plus carboplatin, including lower rates of grade >=3 neutropenia, peripheral neuropathy, arthralgia and myalgia, although was associated with more grade >=3 anaemia and thrombocytopenia. Given its efficacy and tolerability, intravenous nab-paclitaxel plus carboplatin is a valuable first-line treatment option for patients with advanced NSCLC. PMID- 26541765 TI - Sub-wavelength Laser Nanopatterning using Droplet Lenses. AB - When a drop of liquid falls onto a screen, e.g. a cell phone, the pixels lying underneath appear magnified. This lensing effect is a combination of the curvature and refractive index of the liquid droplet. Here, the spontaneous formation of such lenses is exploited to overcome the diffraction limit of a conventional laser direct-writing system. In particular, micro-droplets are first laser-printed at user-defined locations on a surface and they are later used as lenses to focus the same laser beam. Under conditions described herein, nanopatterns can be obtained with a reduction in spot size primarily limited by the refractive index of the liquid. This all-optics approach is demonstrated by writing arbitrary patterns with a feature size around 280 nm, about one fourth of the processing wavelength. PMID- 26541766 TI - Robotic gastrectomy for elderly gastric cancer patients: comparisons with robotic gastrectomy in younger patients and laparoscopic gastrectomy in the elderly. AB - BACKGROUND: Robotic surgery for gastric cancer has been adopted to overcome technical difficulties in performing laparoscopic gastrectomy. This study aimed to investigate the feasibility and safety of robotic gastrectomy in elderly gastric cancer patients. METHODS: Patients who underwent laparoscopic or robotic gastrectomy from 2003 to 2010 in a single high-volume center were included in this study. We retrospectively compared preoperative characteristics, perioperative factors, and oncological parameters among an elderly (>=70 years old) robotic gastrectomy group (n = 49), a younger (<70 years old) robotic gastrectomy group (n = 321), and an elderly laparoscopic gastrectomy group (n = 132). RESULTS: The elderly robotic group presented with more comorbidities than the younger robotic group. Except for number of retrieved lymph nodes (36.5 vs. 41.5; P = 0.007), short-term operative outcomes including complications and pathological parameters were comparable between the two robotic groups. The elderly robotic group showed comparable disease-specific survival to the younger robotic group although overall survival was worse. Compared to their laparoscopic counterparts, the elderly robotic group showed longer mean operation time (227 vs. 174 min). Nevertheless, the incidence and severity of postoperative complications was not different between the two elderly groups. Overall and disease-specific survival were also comparable between the elderly groups. In multivariate analysis, age and surgical approach were not risk factors for overall and major complications. CONCLUSIONS: The outcomes of robotic gastrectomy in the elderly did not differ from those in younger robotic gastrectomy patients and were comparable to those in elderly patients who underwent laparoscopic gastrectomy. Thus, robotic gastrectomy could be a safe and feasible approach in elderly patients. PMID- 26541767 TI - Portomesenteric vein thrombosis after gastric surgery. AB - BACKGROUND: Postoperative portomesenteric venous thrombosis (PMVT) is a rare but potentially serious complication of gastric surgery. This study analyzed the incidence, characteristics, risk factors, and outcomes of PMVT following gastric surgery. METHODS: Medical records of patients who underwent gastric surgery between January 2007 and December 2012 were reviewed retrospectively. The risk factors of PMVT were analyzed by a logistic regression analysis with control group matched 1:4 by age, sex, and cancer stage and by a Poisson regression analysis with unmatched control group. The resolution rate of PMVT in 12 months was compared between the treatment group and the nontreatment group. RESULTS: The total incidence of PMVT after gastric surgery was 0.67 % (31/4611). Most (54.84 %) PMVT cases were detected within 1 month postoperatively. No accompanying deep vein thrombosis (DVT) was noted. Multivariate comparison with 1:4 matched control showed that combined splenectomy, synchronous malignancy, and intra-abdominal complication were independent risk factors. Advanced stage, combined splenectomy, and synchronous malignancy were independent risk factors in Poisson regression analysis using unmatched controls. The resolution rate of PMVT was not different from patients treated with anticoagulation (n = 6) or antiplatelet therapy (n = 1) and were not significantly different with those of the untreated group [85.7 % (6/7) vs. 82.3 % (14/17), p = 0.935] during 1-year follow up. CONCLUSIONS: PMVT after gastric surgery was associated with advanced cancer stage, combined splenectomy, and synchronous malignancy, but it was not related to laparoscopy or DVT. Significant differences in the natural course of PMVT were not found between the treatment group and observation group. PMID- 26541768 TI - Improved survival in resected oesophageal and gastric adenocarcinomas over a decade: the Royal Marsden experience 2001-2010. AB - BACKGROUND: Oesophageal and gastric adenocarcinoma (OGA) treatment remains challenging. Improvements in early diagnosis, staging and management might have contributed to survival prolongation. To examine this hypothesis, we assessed outcomes of resected OGA patients in our institution over 10 years, comparing two time periods, 2001-2005 and 2006-2010. METHODS: Records from patients who had undergone surgery with radical intent and follow-up for OGA were retrospectively reviewed. Patients followed up at hospitals other than the Royal Marsden Hospital were excluded. Two different cohorts were identified: patients with oesophageal and type I or type II oesophagogastric junction (OGJ) tumours, and patients with gastric and type III OGJ tumours. RESULTS: We identified 360 patients: 147 from 2001-2005 and 213 from 2006-2010. The characteristics were comparable across the two time periods. Between 2001-2005 and 2006-2010, the percentage of R0 resections increased (from 67.1 to 81.1 % for proximal tumours and from 76.3 to 95.9 % for gastric and type III OGJ tumours). The mean number of lymph nodes retrieved increased over time. The 5-year overall survival rate increased significantly from 42.3 to 56.6 % for proximal tumours and from 38.8 to 55.3 % for gastric and type III OGJ tumours. Similarly, the disease-free survival rate significantly increased from 34.6 to 53.5 % for proximal tumours and from 35.9 to 51.1 % for gastric and type III OGJ tumours. CONCLUSION: This study comprehensively describes the improvement in survival outcomes in a major UK referral centre over a 10-year period, identifying potentially relevant factors such as increased number of R0 resections and higher lymph node yield. PMID- 26541769 TI - Inflammation-induced oxidative stress in breast cancer patients. AB - Inflammation induced by cytokines has been linked to increased production of reactive oxygen species and breast cancer development. The aim of this study was to evaluate the influence COX-2, IL-1beta, IL-8, and TNF-alpha gene expressions on DNA damage, and investigate a possible link between these factors with neoplastic process. The mRNA expression was measured by real-time PCR, and the DNA damage was analyzed by single-cell gel electrophoresis (comet assay). Our data indicated a significant increase on inflammatory gene expression in tumor tissues compared with normal tissue, and it was also associated with undifferentiated grade patients. Moreover, the results showed that the higher levels of DNA damage were observed among tumor tissue samples. Taken together, the findings presented in this study highlight the relevance of inflammation induced oxidative stress in breast carcinogenesis. PMID- 26541770 TI - High-throughput sexing of mouse blastocysts by real-time PCR using dissociation curves. PMID- 26541771 TI - Ln12 -Containing 60-Tungstogermanates: Synthesis, Structure, Luminescence, and Magnetic Studies. AB - A new class of hexameric Ln12 -containing 60-tungstogermanates, [Na(H2 O)6 ?Eu12 (OH)12 (H2 O)18 Ge2 (GeW10 O38 )6 ](39-) (Eu12 ), [Na(H2 O)6 ?Gd12 (OH)6 (H2 O)24 Ge(GeW10 O38 )6 ](37-) (Gd12 ), and [(H2 O)6 ?Dy12 (H2 O)24 (GeW10 O38 )6 ](36-) (Dy12 ), comprising six di-Ln-embedded {beta(4,11)-GeW10 } subunits was prepared by reaction of [alpha-GeW9 O34 ](10-) with Ln(III) ions in weakly acidic (pH 5) aqueous medium. Depending on the size of the Ln(III) ion, the assemblies feature selective capture of two (for Eu12 ), one (for Gd12 ), or zero (for Dy12 ) extra Ge(IV) ions. The selective encapsulation of a cationic sodium hexaaqua complex [Na(H2 O)6 ](+) was observed for Eu12 and Gd12 , whereas Dy12 incorporates a neutral, distorted-octahedral (H2 O)6 cluster. The three compounds were characterized by single-crystal XRD, ESI-MS, photoluminescence, and magnetic studies. Dy12 was shown to be a single-molecule magnet. PMID- 26541772 TI - Mutant neurogenin-3 in a Turkish boy with congenital malabsorptive diarrhea. AB - Congenital diarrheal disorders are caused by disruption in nutrient digestion, absorption, or transport, enterocyte development and functioning, or enteroendocrine functioning. Many additional rare forms of congenital diarrhea are expected to be linked to genes associated with appropriate intestinal fluid and electrolyte balance. Neurogenin-3 mutation, a very rare form of congenital diarrhea, disrupts enteroendocrine cell differentiation and is characterized by malabsorption and the absence of pancreatic islet cells. Diabetes mellitus is typically associated with malabsorptive diarrhea at early onset or at later presentation in neurogenin-3 mutation. Here, we describe the case of an infant with homozygous neurogenin-3 mutation who had severe malabsorptive diarrhea and episodes of hyperchloremic metabolic acidosis after birth. Remarkably, cholestyramine was effective at reducing stool volume and frequency and improved the consistency of the stools; diabetes was not present in this patient. PMID- 26541773 TI - Imaging Angiogenesis Using 99mTc-Macroaggregated Albumin Scintigraphy in Patients with Peripheral Artery Disease. AB - One problem of vascular angiogenesis therapy is the lack of reliable methods for evaluating blood flow in the microcirculation. We aimed to assess whether (99m)Tc macroaggregated albumin perfusion scintigraphy ((99m)Tc-MAA) predicts quantitated blood flow after therapeutic angiogenesis in patients with peripheral artery disease. METHODS: Forty-six patients with peripheral artery disease were treated with bone marrow mononuclear cell implantation (BMCI). Before and 4 wk after BMCI, blood flow was evaluated via transcutaneous oxygen tension (TcPO2), ankle brachial index, intravenous (99m)Tc-tetrofosmin perfusion scintigraphy ((99m)Tc TF), and intraaortic (99m)Tc-MAA. RESULTS: Four weeks after BMCI, TcPO2 improved significantly (20.4 +/- 14.4 to 36.0 +/- 20.0 mm Hg, P < 0.01), but ankle brachial index did not (0.65 +/- 0.30 to 0.76 +/- 0.24, P = 0.07). Improvement in (99m)Tc-TF count (0.60 +/- 0.23 to 0.77 +/- 0.29 count ratio/pixel, P < 0.01) and (99m)Tc-MAA count (5.21 +/- 3.56 to 10.33 +/- 7.18 count ratio/pixel, P = 0.02) was observed in the foot region but not the lower limb region, using both methods. When these data were normalized by subtracting the pixel count of the untreated side, the improvements in (99m)Tc-TF count (-0.04 +/- 0.26 to 0.08 +/- 0.32 count ratio/pixel, P = 0.04) and (99m)Tc-MAA count (1.49 +/- 3.64 to 5.59 +/ 4.84 count ratio/pixel, P = 0.03) in the foot remained significant. (99m)Tc-MAA indicated that the newly developed arteries were approximately 25 MUm in diameter. CONCLUSION: BMCI induced angiogenesis in the foot, which was detected using (99m)Tc-TF and (99m)Tc-MAA. (99m)Tc-MAA is a useful method to quantitate blood flow, estimate vascular size, and evaluate flow distribution after therapeutic angiogenesis. PMID- 26541774 TI - 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. AB - Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives. METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117. CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients. PMID- 26541775 TI - 18F-FDG PET/CT for the Diagnosis of Residual or Recurrent Nasopharyngeal Carcinoma After Radiotherapy: A Metaanalysis. AB - The aim of this work was to assess the overall value of (18)F-FDG PET/CT in the diagnosis of residual or recurrent nasopharyngeal carcinoma using a metaanalysis. METHODS: The literature published between January 1990 and September 2014 was searched in the PubMed, EMBASE, Cochrane Library, EBSCO, VIP, CNKI, and Wanfang databases to identify eligible studies on PET/CT of residual or recurrent lesions. The methodologic quality of the included studies was evaluated using the "quality assessment for studies of diagnostic accuracy" tool. Summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and receiver-operating characteristic curve were obtained using Meta-DiSc freeware. Subgroups were also analyzed. RESULTS: A total of 23 studies, involving 1,253 subjects, were included in the metaanalysis. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, with 95% confidence intervals in parentheses, for (18)F-FDG PET or PET/CT were 0.93 (0.91-0.95), 0.87 (0.84-0.89), 5.52 (3.96 7.71), 0.12 (0.09-0.15), and 55.31 (34.94-87.57), respectively. The area under the receiver-operating characteristic curve and Q* index estimate of PET/CT were 0.9473 and 0.8869, respectively. There was no significant difference between the area under the curve of PET and PET/CT (P > 0.05). CONCLUSION: Our study has confirmed that (18)F-FDG PET/CT has high sensitivity and specificity but significant heterogeneity in the diagnosis of residual or recurrent nasopharyngeal carcinoma. PMID- 26541776 TI - Partial-Volume Effect Correction Improves Quantitative Analysis of 18F Florbetaben beta-Amyloid PET Scans. AB - Neocortical atrophy reduces PET signal intensity, potentially affecting the diagnostic efficacy of beta-amyloid (Abeta) brain PET imaging. This study investigated whether partial-volume effect correction (PVEC), adjusting for this atrophy bias, improves the accuracy of (18)F-florbetaben Abeta PET. METHODS: We analyzed (18)F-florbetaben PET and MRI data obtained from 3 cohorts. The first was 10 patients with probable Alzheimer disease (AD) and 10 age-matched healthy controls (HCs), the second was 31 subjects who underwent in vivo imaging and postmortem histopathology for Abeta plaques, and the third was 5 subjects who underwent PET and MRI at baseline and 1 y later. The imaging data were coregistered and segmented. PVEC was performed using the voxel-based modified Muller-Gartner method (PVELab, SPM8). From the PET data, regional and composite SUV ratios (SUVRs) with and without PVEC were obtained. In the MRI data, mesial temporal lobe atrophy was determined by the Scheltens mesial temporal atrophy scale and gray matter volumes by voxel-based morphometry. RESULTS: In cohort 1, PVEC increased the effect on AD-versus-HC discrimination from a Cohen d value of 1.68 to 2.0 for composite SUVRs and from 0.04 to 1.04 for mesial temporal cortex SUVRs. The PVEC-related increase in mesial temporal cortex SUVR correlated with the Scheltens score (r = 0.84, P < 0.001), and that of composite SUVR correlated with the composite gray matter volume (r = -0.75, P < 0.001). In cohort 2, PVEC increased the correlation coefficient between mesial temporal cortex SUVR and histopathology score for Abeta plaque load from 0.28 (P = 0.09) to 0.37 (P = 0.03). In cohort 3, PVEC did not affect the composite SUVR dynamics over time for the Abeta-negative subject. This finding was in contrast to the 4 Abeta-positive subjects, in 2 of whom PVEC changed the composite SUVR dynamics. CONCLUSION: The influence of PVEC on (18)F-florbetaben PET data is associated with the degree of brain atrophy. Thus, PVEC increases the ability of (18)F-florbetaben PET to discriminate between AD patients and HCs, to detect Abeta plaques in the atrophic mesial temporal cortex, and potentially to evaluate changes in brain Abeta load over time. As such, the use of PVEC should be considered for quantitative (18)F florbetaben PET scans, especially in assessing patients with brain atrophy. PMID- 26541777 TI - Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology. AB - Acetylcholinesterase and butyrylcholinesterase accumulate with brain beta-amyloid (Abeta) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Abeta plaques within the brain, cholinesterase associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Abeta plaques has the potential to distinguish AD from cognitively normal older adults, with or without Abeta accumulation, during life. Current Abeta imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I PIP), is described. METHODS: Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Abeta imaging agent, 2-(4' dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Abeta and cholinesterase activity to visualize Abeta plaque load for comparison with radioligand uptake. RESULTS: Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Abeta plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Abeta plaques from both AD and cognitively normal individuals. CONCLUSION: Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I PIP, can detect cholinesterases associated with Abeta plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Abeta plaques. Imaging cholinesterase activity associated with Abeta plaques in the living brain may contribute to the definitive diagnosis of AD during life. PMID- 26541779 TI - New Insights: PET Imaging to Document Synergistic Therapy Effect of the "Old," Ancient Recipe and the "New," Modern Drug in Stroke. PMID- 26541778 TI - PET Imaging of VEGFR-2 Expression in Lung Cancer with 64Cu-Labeled Ramucirumab. AB - Lung cancer accounts for 17% of cancer-related deaths worldwide, and most patients present with locally advanced or metastatic disease. Novel PET imaging agents for assessing vascular endothelial growth factor receptor-2 (VEGFR-2) expression can be used for detecting VEGFR-2-positive malignancies and subsequent monitoring of therapeutic response to VEGFR-2-targeted therapies. Here, we report the synthesis and characterization of an antibody-based imaging agent for PET imaging of VEGFR-2 expression in vivo. METHODS: Ramucirumab (named RamAb), a fully humanized IgG1 monoclonal antibody, was conjugated to 2-S-(4 isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn NOTA) and labeled with (64)Cu. Flow cytometry analysis and microscopy studies were performed to compare the VEGFR-2 binding affinity of RamAb and NOTA-RamAb. PET imaging and biodistribution studies were performed in nude mice bearing HCC4006 and A549 xenograft tumors. Ex vivo histopathology was performed to elucidate the expression patterns of VEGFR-2 in different tissues and organs to validate in vivo results. RESULTS: Flow cytometry examination revealed the specific binding capacity of fluorescein isothiocyanate-RamAb to VEGFR-2, and no difference in VEGFR-2 binding affinity was seen between RamAb and NOTA-RamAb. After being labeled with (64)Cu, PET imaging revealed specific and prominent uptake of (64)Cu-NOTA-RamAb in VEGFR-2-positive HCC4006 tumors (9.4 +/- 0.5 percentage injected dose per gram at 48 h after injection; n = 4) and significantly lower uptake in VEGFR-2-negative A549 tumors (4.3 +/- 0.2 percentage injected dose per gram at 48 h after injection; n = 3). Blocking experiments revealed significantly lower uptake in HCC4006 tumors, along with histology analysis, further confirming the VEGFR-2 specificity of (64)Cu-NOTA RamAb. CONCLUSION: This study provides initial evidence that (64)Cu-NOTA-RamAb can function as a PET imaging agent for visualizing VEGFR-2 expression in vivo, which may also find potential applications in monitoring the treatment response of VEGFR-2-targeted cancer therapy. PMID- 26541782 TI - Face-Capped M(4) L4 Tetrahedral Metal-Organic Cage: Iodine Capture and Release, Ion Exchange, and Electrical Conductivity. AB - An M(4) L4 type metal-organic cage (MOC-19) has been synthesized from the one-pot reaction of tri(pyridinylmethylene)phenylbenzeneamine (TPBA) with hydrated Zn(ClO4 )2 under mild conditions and characterized by single-crystal X-Ray diffraction. Iodine capture studies show that the porous crystals of MOC-19 exhibit a versatile behavior to accumulate iodine species not only in vapor (for I2 ) but also in solution (for I2 and I3 (-) ), and anion-exchange experiments indicate the capacity to extract IO3 (-) anions from aqueous solution. Enrichment of iodine species from KI/I2 aqueous solution proceeds facilely, revealing a pseudo-second-order kinetics of I3 (-) adsorption. Furthermore, the electrical conductivity of MOC-19 single crystals could be significantly altered by I2 inclusion. PMID- 26541780 TI - New Approaches to Molecular Imaging of Multiple Myeloma. AB - Molecular imaging plays an important role in detection and staging of hematologic malignancies. Multiple myeloma (MM) is an age-related hematologic malignancy of clonal bone marrow plasma cells characterized by destructive bone lesions and is fatal in most patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Progressive biomedical imaging technologies such as low-dose CT, molecularly targeted PET, MRI, and the functional-anatomic hybrid versions (PET/CT and PET/MRI) provide incremental advancements in imaging MM. Imaging with PET and MRI using molecularly targeted probes is a promising precision medicine platform that might successfully address the clinical ambiguities of myeloma spectrum diseases. The intent of this focus article is to provide a concise review of the present status and promising developments on the horizon, such as the new molecular imaging biomarkers under investigation that can either complement or potentially supersede existing standards. PMID- 26541783 TI - Retrospective complication rate comparison between surgical techniques in paediatric cochlear implantation. AB - OBJECTIVE: To compare paediatric complication occurrence between the Mastoidectomy with Posterior Tympanotomy and the SupraMeatal Approach for cochlear implantation. DESIGN: Retrospective cohort study. SETTING: Children receiving a cochlear implant before 5 years of age between 1996 and 2014 in our tertiary center. PARTICIPANTS: A total of 144 patients receiving a cochlear implant (121 by Mastoidectomy with Posterior Tympanotomy and 23 by SupraMeatal Approach) operated on 165 ears (129 and 39 respectively). MAIN OUTCOME MEASURES: The severity (minor or major) using Cohen and Hoffman criteria and time of occurrence of complications (intraoperative, early postoperative or late postoperative) were identified. Intraoperative surgical challenges were correlated to complication occurrence. RESULTS: The mean age at implantation was 2.13 +/- 1.14 years old. Patients operated by the SupraMeatal Approach (1.27 +/- 0.69 years old) were significantly (P < .001) younger than those receiving a cochlear implant by Mastoidectomy with Posterior Tympanotomy Approach (2.40 +/- 1.12). Most complications were minor (Mastoidectomy with Posterior Tympanotomy Approach: 64.0%; SupraMeatal Approach: 73.1%) and occurred early postoperatively (Mastoidectomy with Posterior Tympanotomy Approach: 61.5%; SupraMeatal Approach: 76.9%). More overall complications occurred in SupraMeatal compared to Mastoidectomy with Posterior Tympanotomy Approach cases (61.5% versus 20.6%; P < .001). Younger SupraMeatal Approach cohort patients (6 - 12 and 18 - 24 months; P < .008 and P = .016) most often developed these complications. When looking at specific complications, more infectious complications occurred in patients receiving a cochlear implant through the SupraMeatal Approach (P < .05). Logistic regression showed that the surgical technique and not the age at implantation was responsible for the documented complications. No relationship between complications and intraoperative difficulties was identified. CONCLUSION: In our institution, cochlear implantation in young patients through the SupraMeatal Approach resulted in significantly more (infectious) complications than those operated through the Mastoidectomy with Posterior Tympanotomy Approach. Outcomes from our institution recommends using the Mastoidectomy with Posterior Tympanotomy Approach when opting for a cochlear implant surgical technique in young children who are more prone to develop infectious complications. PMID- 26541784 TI - Long-term effect of mass chemotherapy of Schistosoma mansoni on infection rate and diagnosis accuracy. AB - OBJECTIVES: To assess the performance of microscopic stool examination, which is used widely for the diagnosis and assessment of infection rates of Schistosoma mansoni in Egypt, for the evaluation of chemotherapy efficacy after a decade of regular mass treatment. METHODS: A total of 651 individuals from Lower Egypt (55 children and 596 adults) were examined for S. mansoni ova by microscopic stool examination (MSE) alone (n=166; 111 adults and 55 children), rectal biopsy (RB) alone (n=32 adults), or both MSE and RB (n=453 adults). RESULTS: Infection detection rates were significantly lower in the MSE alone group (9%; 15/166) compared to the RB alone group (40.6%; 13/32) and to the RB+MSE group (37.7%; 171/453). Out of all positive cases in the MSE+RB group, only 23/171 patients (13.5%) were positive by stool examination, of whom 21 were also positive by RB, in contrast to 169/171 patients (86.5%) positive by RB in the same group. It was noted that adding MSE to RB did not increase the prevalence compared to RB alone: 37.3% in the MSE+RB group vs. 40.6% in the RB only group. Using the summation of both MSE and RB tests as the gold standard, the sensitivity of MSE was significantly lower than that of RB: 13.5% vs. 98.8%. CONCLUSIONS: The implementation of mass treatment programmes has resulted in a new era of light infection, for which conventional parasitological methods for the diagnosis and monitoring of infection can miss many patients. PMID- 26541785 TI - Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction. AB - OBJECTIVES: This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size. BACKGROUND: Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia-reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1alpha is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3beta. METHODS: AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1 degrees Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1 degrees Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified. RESULTS: Compared with 1 degrees Reperfusion, 1 degrees Unloading reduced LV wall stress and increased myocardial levels of SDF-1alpha, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase 3beta in the infarct zone. 1 degrees Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1 degrees Reperfusion (73 +/- 13% vs. 42 +/- 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01). CONCLUSIONS: Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up regulates SDF-1alpha/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI. PMID- 26541786 TI - Limiting Infarct Size in ST-Segment Myocardial Infarction: The Holy Grail of Reperfusion Therapy. PMID- 26541787 TI - Prognostic Value of Estimated Plasma Volume in Heart Failure. AB - OBJECTIVES: The purpose of this study was to assess the prognostic value of the estimation of plasma volume or of its variation beyond clinical examination in a post-hoc analysis of EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). BACKGROUND: Assessing congestion after discharge is challenging but of paramount importance to optimize patient management and to prevent hospital readmissions. METHODS: The present analysis was performed in a subset of 4,957 patients with available data (within a full dataset of 6,632 patients). The study endpoint was cardiovascular death or hospitalization for heart failure (HF) between months 1 and 3 after post-acute myocardial infarction HF. Estimated plasma volume variation (DeltaePVS) between baseline and month 1 was estimated by the Strauss formula, which includes hemoglobin and hematocrit ratios. Other potential predictors, including congestion surrogates, hemodynamic and renal variables, and medical history variables, were tested. An instantaneous estimation of plasma volume at month 1 was defined and also tested. RESULTS: Multivariate analysis was performed with stepwise logistic regression. DeltaePVS was selected in the model (odds ratio: 1.01; p = 0.004). The corresponding prognostic gain measured by integrated discrimination improvement was significant (7.57%; p = 0.01). Nevertheless, instantaneous estimation of plasma volume at month 1 was found to be a better predictor than DeltaePVS. CONCLUSIONS: In HF complicating myocardial infarction, congestion as assessed by the Strauss formula and an instantaneous derived measurement of plasma volume provided a predictive value of early cardiovascular events beyond routine clinical assessment. Prospective trials to assess congestion management guided by this simple tool to monitor plasma volume are warranted. PMID- 26541788 TI - Tackling Early Heart Failure Deaths and Readmissions by Estimating Congestion. PMID- 26541789 TI - Bundle Up for Value-Based Heart Failure Care. PMID- 26541790 TI - Extending landscape of volatile metabolites as novel diagnostic biomarkers of inflammatory bowel disease - a review. AB - The diagnosis of inflammatory bowel disease (IBD) remains a challenging task despite significant increase in the understanding of the disease aetiology and pathogenesis. Recent decade has seen a massive interest in the non-invasive diagnostic biomarkers of IBD, consequently a number of studies have explored a variety of potential biomarkers to diagnose the disease and monitor the disease activity. Volatile metabolites are the chemicals, which emanate from biological fluids and can reflect the status of health and disease of an individual. Recent advances in the analytical techniques have enabled the detection and interpretation of the changes in volatile metabolites in breath, urine, faeces and blood of an individual in correlation with various gastrointestinal (GI) disorders including IBD. This can provide a simple, fast and reproducible diagnosis at the point of care. This review focuses on the current and future novel approaches for detecting and the monitoring gut inflammation in IBD by using volatile organic metabolites. PMID- 26541791 TI - New therapeutic strategies regarding endovascular treatment of glioblastoma, the role of the blood-brain barrier and new ways to bypass it. AB - The treatment protocols for glioblastoma multiforme (GBM) involve a combination of surgery, radiotherapy and adjuvant chemotherapy. Despite this multimodal approach, the prognosis of patients with GBM remains poor and there is an urgent need to develop novel strategies to improve quality of life and survival in this population. In an effort to improve outcomes, intra-arterial drug delivery has been used in many recent clinical trials; however, their results have been conflicting. The blood-brain barrier (BBB) is the major obstacle preventing adequate concentrations of chemotherapy agents being reached in tumor tissue, regardless of the method of delivering the drugs. Therapeutic failures have often been attributed to an inability of drugs to cross the BBB. However, during the last decade, a better understanding of BBB physiology along with the development of new technologies has led to innovative methods to circumvent this barrier. This paper focuses on strategies and techniques used to bypass the BBB already tested in clinical trials in humans and also those in their preclinical stage. We also discuss future therapeutic scenarios, including endovascular treatment combined with BBB disruption techniques, for patients with GBM. PMID- 26541792 TI - Molecularly imprinted polymeric stir bar: Preparation and application for the determination of naftopidil in plasma and urine samples. AB - In this study, molecularly imprinting technology and stir bar absorption technology were combined to develop a microextraction approach based on a molecularly imprinted polymeric stir bar. The molecularly imprinted polymer stir bar has a high performance, is specific, economical, and simple to prepare. The obtained naftopidil-imprinted polymer-coated bars could simultaneously agitate and adsorb naftopidil in the sample solution. The ratio of template/monomer/cross linker and conditions of template removal were optimized to prepare a stir bar with highly efficient adsorption. Fourier transform infrared spectroscopy, scanning electron microscopy, selectivity, and extraction capacity experiments showed that the molecularly imprinted polymer stir bar was prepared successfully. To utilize the molecularly imprinted polymer stir bar for the determination of naftopidil in complex body fluid matrices, the extraction time, stirring speed, eluent, and elution time were optimized. The limits of detection of naftopidil in plasma and urine sample were 7.5 and 4.0 ng/mL, respectively, and the recoveries were in the range of 90-112%. The within-run precision and between-run precision were acceptable (relative standard deviation <7%). These data demonstrated that the molecularly imprinted polymeric stir bar based microextraction with high performance liquid chromatography was a convenient, rapid, efficient, and specific method for the precise determination of trace naftopidil in clinical analysis. PMID- 26541793 TI - Simultaneous effective carbon and nitrogen removals and phosphorus recovery in an intermittently aerated membrane bioreactor integrated system. AB - Recovering nutrients, especially phosphate resource, from wastewater have attracted increasing interest recently. Herein, an intermittently aerated membrane bioreactor (MBR) with a mesh filter was developed for simultaneous chemical oxygen demand (COD), total nitrogen (TN) and phosphorous removal, followed by phosphorus recovery from the phosphorus-rich sludge. This integrated system showed enhanced performances in nitrification and denitrification and phosphorous removal without excess sludge discharged. The removal of COD, TN and total phosphorus (TP) in a modified MBR were averaged at 94.4 +/- 2.5%, 94.2 +/- 5.7% and 53.3 +/- 29.7%, respectively. The removed TP was stored in biomass, and 68.7% of the stored phosphorous in the sludge could be recovered as concentrated phosphate solution with a concentration of phosphate above 350 mg/L. The sludge after phosphorus release could be returned back to the MBR for phosphorus uptake, and 83.8% of its capacity could be recovered. PMID- 26541794 TI - Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice. AB - Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). It could also up-regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator activated receptor alpha (PPARalpha) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose-6-phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD-induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues. PMID- 26541795 TI - Localized atrophy of the thalamus and slowed cognitive processing speed in MS patients. AB - BACKGROUND: Deep gray matter (DGM) atrophy is common in multiple sclerosis (MS), but no studies have investigated surface-based structure changes over time with respect to healthy controls (HCs). Moreover, the relationship between cognition and the spatio-temporal evolution of DGM atrophy is poorly understood. OBJECTIVES: To explore DGM structural differences between MS and HCs over time in relation to neuropsychological (NP) outcomes. METHODS: The participants were 44 relapsing-remitting and 20 secondary progressive MS patients and 22 HCs. All were scanned using 3T magnetic resonance imaging (MRI) at baseline and 3-year follow up. NP examination emphasized consensus standard tests of processing speed and memory. We performed both volumetric and shape analysis of DGM structures and assessed their relationships with cognition. RESULTS: Compared to HCs, MS patients presented with significantly smaller DGM volumes. For the thalamus and caudate, differences in shape were mostly localized along the lateral ventricles. NP outcomes were related to both volume and shape of the DGM structures. Over 3 years, decreased cognitive processing speed was related to localized atrophy on the anterior and superior surface of the left thalamus. CONCLUSIONS: These findings highlight the role of atrophy in the anterior nucleus of the thalamus and its relation to cognitive decline in MS. PMID- 26541796 TI - Self-reported cue-induced physical symptoms of craving as an indicator of cocaine dependence. AB - BACKGROUND: The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians. OBJECTIVE: To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence. METHODS: A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0-5 scale. RESULTS: The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of >= 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R(2) increased from .149 to .326 (p < .001). DISCUSSION AND CONCLUSION: Recalling past experiences of cue-induced physical signs of cocaine craving is associated with a clinical diagnosis of lifetime cocaine dependence and could be a simple way to improve its detection in clinical settings. PMID- 26541797 TI - Professionalism in interventional cardiology and the new value-based payment system. PMID- 26541798 TI - Ageless benefits of transradial access for percutaneous coronary revascularization. PMID- 26541799 TI - Implantation of everolimus-eluting bioresorbable scaffolds in a diabetic all comers population--the future is now? PMID- 26541800 TI - Refining rather than redefining the BVS in "real world". PMID- 26541801 TI - When a stent gets shorty. PMID- 26541802 TI - Will invasive coronary imaging identify vulnerable plaque and predict future cardiac events? PMID- 26541803 TI - Closure of the patent foramen ovale, perhaps the best thing interventional cardiology has to offer. PMID- 26541804 TI - Emulsification at the Liquid/Liquid Interface: Effects of Potential, Electrolytes and Surfactants. AB - Emulsification of oils at liquid/liquid interfaces is of fundamental importance across a range of applications, including detergency. Adsorption and partitioning of the anionic surface active ions at the interface between two immiscible solutions is known to cause predictable chaos at the transfer potential region of the surfactant. In this work, the phenomenon that leads to the chaotic behaviour shown by sodium dodecylbenzene sulfonate (SDBS) at the water/1,2-dichloroethane interface is applied to commercial surfactants and aqueous/glyceryl trioleate interface. Electrochemical methods, electrocapillary curves, optical microscopy and conductivity measurements demonstrated that at 1.5 mm of SDBS, surfactants are adsorbed at the interface and assemble into micelles, leading to interfacial instability. As the concentration of the anionic surfactant was enhanced to 8 and 13.4 mm, the Marangoni effect and the interfacial emulsification became more prominent. The chaotic behaviour was found to be dependent on the surfactant concentration and the electrolytes present. PMID- 26541805 TI - V-Y and rectangular flap combination for syndactyly repair. AB - OBJECTIVE: For syndactyly repair, several delicate, well-planned flap combination techniques have been reported. This study presents technique details with functional and aesthetic results of a dorsal rectangular and volar V-Y advancement flap combination for web reconstruction and S incisions for finger separation in patients with syndactyly. METHOD: Ten patients with 16 syndactyly webs were treated. Patients were examined in terms of function and aesthetic. Evaluation criteria included the Vancouver Scar Scale, range of motion, degree of web creeping, parent's satisfaction rates, and finger abduction. During the initial period, vascular compromise of fingers, haematoma, infection, seroma, flap necrosis, or graft failures were not noted in any patients. No patients required revision surgery. During the later period, parent satisfaction scores were excellent or good, finger function was complete, and the Vancouver Scar Scale showed that two webs had hyperpigmented areas and two had supple pliability. CONCLUSION: This simple syndactyly release technique can provide a low rate of web creep, good scar quality, and optimal functional results. PMID- 26541806 TI - Music identification skills of children with specific language impairment. AB - BACKGROUND: To date very few studies have investigated the musical skills of children with specific language impairment (SLI). There is growing evidence that SLI affects areas other than language, and it is therefore reasonable to hypothesize that children with this disorder may have difficulties in perceiving musical stimuli appropriately. AIMS: To compare melody and song identification skills in a group of children with SLI and in a control group of children with typical language development (TD); and to study possible correlations between music identification skills and language abilities in the SLI group. METHODS & PROCEDURES: This is a prospective case control study. Two groups of children were enrolled: one meeting DSM-IV-TR((r)) diagnostic criteria for SLI and the other comprising an age-matched group of children with TD. All children received a melody and a song identification test, together with a test battery assessing receptive and productive language abilities. OUTCOMES & RESULTS: 30 children with SLI (mean age = 56 +/- 9 months) and 23 with TD (mean age = 60 +/- 10 months) were included. Melody and song identification scores among SLI children were significantly lower than those of TD children, and in both groups song identification scores were significantly higher than melody identification scores. Song identification skills bore a significant correlation to chronological age in both groups (TD: r = 0.529, p = 0.009; SLI: r = 0.506, p = 0.004). Whereas no other variables were found explaining the variability of melody or song identification scores in either group, the correlation between language comprehension and song identification in the SLI group approached significance (r = 0.166, p = 0.076). CONCLUSIONS & IMPLICATIONS: The poorer music perception skills of SLI children as compared with TD ones suggests that SLI may also affect music perception. Therefore, training programmes that simultaneously stimulate via language and music may prove useful in the rehabilitation of children affected by SLI. PMID- 26541807 TI - Hantavirus pulmonary syndrome and rodent reservoirs in the savanna-like biome of Brazil's southeastern region. AB - This paper describes the diversity of rodent fauna in an area endemic for hantavirus cardiopulmonary syndrome (HCPS) in Brazil, the population dynamics and the relationship of rodents with hantavirus in the Cerrado (savanna-like) biome. Additionally, an analysis is made of the partial S segment sequences of the hantaviruses obtained from serologically confirmed human HCPS cases and from rodent specimens. Rodents were collected during four campaigns. Human serum samples were collected from suspected cases of HCPS at hospitals in the state of Minas Gerais. The samples antibody-reactive by ELISA were processed by RT-PCR. The PCR product was amplified and sequenced. Hantavirus was detected only in Necromys lasiurus, the wild rodent species most prevalent in the Cerrado biome (min-max: 50-83.7%). All the six human serum samples were hantavirus seropositive and five showed amplified PCR products. The analysis of the nucleotide sequences showed the circulation of a single genotype, the Araraquara hantavirus. The environmental changes that have occurred in the Cerrado biome in recent decades have favoured N. lasiurus in interspecific competition of habitats, thus increasing the risk of contact between humans and rodent species infected with hantavirus. Our data corroborate the definition of N. lasiurus as the main hantavirus reservoir in the Cerrado biome. PMID- 26541808 TI - Impact of arrhythmia on diagnostic performance of adenosine stress CMR in patients with suspected or known coronary artery disease. AB - BACKGROUND: The diagnostic performance of adenosine stress cardiovascular magnetic resonance (CMR) in patients with arrhythmias presenting for work-up of suspected or known CAD is largely unknown, since most CMR studies currently available exclude arrhythmic patients from analysis fearing gating problems, or other artifacts will impair image quality. The primary aim of our study was to evaluate the diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for 1) work up of suspected coronary artery disease (CAD), or 2) work-up of ischemia in known CAD. METHODS: Patients with arrhythmia referred for work-up of suspected CAD or work-up of ischemia in known CAD undergoing adenosine stress CMR were included if they had coronary angiography within four weeks of CMR. RESULTS: One hundred fifty-nine patients were included (n = 64 atrial fibrillation, n = 87 frequent ventricular extrasystoles, n = 8 frequent supraventricular extrasystoles). Of these, n = 72 had suspected CAD, and n = 87 had known CAD. Diagnostic accuracy of the adenosine stress CMR for detection of significant CAD was 73 % for the entire population (sensitivity 72 %, specificity 76 %). Diagnostic accuracy was 75 % (sensitivity 80 %, specificity 74 %) in patients with suspected CAD, and 74 % (sensitivity 71 %, specificity 79 %) in the group with known CAD. For different types of arrhythmia, diagnostic accuracy of CMR was 70 % in the atrial fibrillation group, and 79 % in patients with ventricular extrasystoles. On a per coronary territory analysis, diagnostic accuracy of CMR was 77 % for stenosis of the left and 82 % for stenosis of the right coronary artery. CONCLUSION: The present data demonstrates good diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for work-up of suspected CAD, or work-up of ischemia in known CAD. This holds true for a per patient, as well as for a per coronary territory analysis. PMID- 26541809 TI - Global effects of agriculture on fluvial dissolved organic matter. AB - Agricultural land covers approximately 40% of Earth's land surface and affects hydromorphological, biogeochemical and ecological characteristics of fluvial networks. In the northern temperate region, agriculture also strongly affects the amount and molecular composition of dissolved organic matter (DOM), which constitutes the main vector of carbon transport from soils to fluvial networks and to the sea, and is involved in a large variety of biogeochemical processes. Here, we provide first evidence about the wider occurrence of agricultural impacts on the concentration and composition of fluvial DOM across climate zones of the northern and southern hemispheres. Both extensive and intensive farming altered fluvial DOM towards a more microbial and less plant-derived composition. Moreover, intensive farming significantly increased dissolved organic nitrogen (DON) concentrations. The DOM composition change and DON concentration increase differed among climate zones and could be related to the intensity of current and historical nitrogen fertilizer use. As a result of agriculture intensification, increased DON concentrations and a more microbial-like DOM composition likely will enhance the reactivity of catchment DOM emissions, thereby fuelling the biogeochemical processing in fluvial networks, and resulting in higher ecosystem productivity and CO2 outgassing. PMID- 26541810 TI - Targeting extra-oral bitter taste receptors modulates gastrointestinal motility with effects on satiation. AB - Bitter taste receptors (TAS2Rs) are present in extra-oral tissues, including gut endocrine cells. This study explored the presence and mechanism of action of TAS2R agonists on gut smooth muscle in vitro and investigated functional effects of intra-gastric administration of TAS2R agonists on gastric motility and satiation. TAS2Rs and taste signalling elements were expressed in smooth muscle tissue along the mouse gut and in human gastric smooth muscle cells (hGSMC). Bitter tastants induced concentration and region-dependent contractility changes in mouse intestinal muscle strips. Contractions induced by denatonium benzoate (DB) in gastric fundus were mediated via increases in intracellular Ca(2+) release and extracellular Ca(2+)-influx, partially masked by a hyperpolarizing K(+)-efflux. Intra-gastric administration of DB in mice induced a TAS2R-dependent delay in gastric emptying. In hGSMC, bitter compounds evoked Ca(2+)-rises and increased ERK-phosphorylation. Healthy volunteers showed an impaired fundic relaxation in response to nutrient infusion and a decreased nutrient volume tolerance and increased satiation during an oral nutrient challenge test after intra-gastric DB administration. These findings suggest a potential role for intestinal TAS2Rs as therapeutic targets to alter gastrointestinal motility and hence to interfere with hunger signalling. PMID- 26541811 TI - The effect of intrinsic crumpling on the mechanics of free-standing graphene. AB - Free-standing graphene is inherently crumpled in the out-of-plane direction due to dynamic flexural phonons and static wrinkling. We explore the consequences of this crumpling on the effective mechanical constants of graphene. We develop a sensitive experimental approach to probe stretching of graphene membranes under low applied stress at cryogenic to room temperatures. We find that the in-plane stiffness of graphene is 20-100 N m(-1) at room temperature, much smaller than 340 N m(-1) (the value expected for flat graphene). Moreover, while the in-plane stiffness only increases moderately when the devices are cooled down to 10 K, it approaches 300 N m(-1) when the aspect ratio of graphene membranes is increased. These results indicate that softening of graphene at temperatures <400 K is caused by static wrinkling, with only a small contribution due to flexural phonons. Together, these results explain the large variation in reported mechanical constants of graphene devices and pave the way towards controlling their mechanical properties. PMID- 26541813 TI - Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality. AB - OBJECTIVE: In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset. METHOD: Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined. RESULTS: During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >-0.38) and percent of positive specific memories recalled (r values >0.59). CONCLUSIONS: The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments targeting amygdala hypoactivity and blunted salience during positive autobiographical recall could exert antidepressant effects. PMID- 26541812 TI - Preventing anxiety problems in children with Cool Little Kids Online: study protocol for a randomised controlled trial. AB - BACKGROUND: Anxiety disorders are the most common type of mental health problem and begin early in life. Early intervention to prevent anxiety problems in young children who are at risk has the potential for long-term impact. The 'Cool Little Kids' parenting group program was previously established to prevent anxiety disorders in young children at risk because of inhibited temperament. This group program was efficacious in two randomised controlled trials and has recently been adapted into an online format. 'Cool Little Kids Online' was developed to widen and facilitate access to the group program's preventive content. A pilot evaluation of the online program demonstrated its perceived utility and acceptability among parents. This study aims to evaluate the efficacy of Cool Little Kids Online in a large randomised controlled trial. METHODS/DESIGN: Parents of young children who are 3-6 years old and who have an inhibited temperament will be recruited (n = 385) and randomly assigned to either immediate access to Cool Little Kids Online or delayed access after a waiting period of 24 weeks. The online program contains eight modules that help parents address key issues in the development of anxiety problems in inhibited children, including children's avoidant coping styles, overprotective parenting behaviours, and parents' own fears and worries. Intervention participants will be offered clinician support when requested. The primary outcome will be change in parent reported child anxiety symptoms. Secondary outcomes will be child internalising symptoms, child and family life interference due to anxiety, over involved/protective parenting, plus child anxiety diagnoses assessed by using a new online diagnostic tool. Assessments will take place at baseline and 12 and 24 weeks after baseline. DISCUSSION: This trial expands upon previous research on the Cool Little Kids parenting group program and will evaluate the efficacy of online delivery. Online delivery of the program could result in an easily accessible evidence-based resource to help families with young children at temperamental risk for anxiety disorders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 12615000217505 (registered 5 March 2015). PMID- 26541814 TI - An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression. AB - OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression. METHOD: This was an 8-week multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population. RESULTS: The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo; the least squares mean difference was 4.0 (95% CI=-6.3, -1.6; significant after adjustment for multiple comparisons). Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo ( 2.5, 95% CI=-4.9, -0.1; not significant when adjusted for multiple comparisons). The 0.75 mg/day dosage was similar to placebo. A similar pattern for significance was observed on the CGI-S (1.5 mg/day: least squares mean difference=-0.4, 95% CI=-0.6, -0.1; 3.0 mg/day: -0.3, 95% CI=-0.5, -0.0). The most common adverse events (>=10%) in cariprazine-treated patients were akathisia and insomnia; weight gain was slightly higher with cariprazine than with placebo. CONCLUSIONS: Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression. PMID- 26541815 TI - Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia. AB - OBJECTIVE: The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice. METHOD: U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality. RESULTS: Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44). CONCLUSIONS: In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects. PMID- 26541816 TI - MetAnnotate: function-specific taxonomic profiling and comparison of metagenomes. AB - BACKGROUND: Metagenomes provide access to the taxonomic composition and functional capabilities of microbial communities. Although metagenomic analysis methods exist for estimating overall community composition or metabolic potential, identifying specific taxa that encode specific functions or pathways of interest can be more challenging. Here we present MetAnnotate, which addresses the common question: "which organisms perform my function of interest within my metagenome(s) of interest?" MetAnnotate uses profile hidden Markov models to analyze shotgun metagenomes for genes and pathways of interest, classifies retrieved sequences either through a phylogenetic placement or best hit approach, and enables comparison of these profiles between metagenomes. RESULTS: Based on a simulated metagenome dataset, the tool achieves high taxonomic classification accuracy for a broad range of genes, including both markers of community abundance and specific biological pathways. Lastly, we demonstrate MetAnnotate by analyzing for cobalamin (vitamin B12) synthesis genes across hundreds of aquatic metagenomes in a fraction of the time required by the commonly used Basic Local Alignment Search Tool top hit approach. CONCLUSIONS: MetAnnotate is multi threaded and installable as a local web application or command-line tool on Linux systems. Metannotate is a useful framework for general and/or function-specific taxonomic profiling and comparison of metagenomes. PMID- 26541817 TI - Effects of in vitro endochondral priming and pre-vascularisation of human MSC cellular aggregates in vivo. AB - INTRODUCTION: During endochondral ossification, both the production of a cartilage template and the subsequent vascularisation of that template are essential precursors to bone tissue formation. Recent studies have found the application of both chondrogenic and vascular priming of mesenchymal stem cells (MSCs) enhanced the mineralisation potential of MSCs in vitro whilst also allowing for immature vessel formation. However, the in vivo viability, vascularisation and mineralisation potential of MSC aggregates that have been pre conditioned in vitro by a combination of chondrogenic and vascular priming, has yet to be established. In this study, we test the hypothesis that a tissue regeneration approach that incorporates both chondrogenic priming of MSCs, to first form a cartilage template, and subsequent pre-vascularisation of the cartilage constructs, by co-culture with human umbilical vein endothelial cells (HUVECs) in vitro, will improve vessel infiltration and thus mineral formation once implanted in vivo. METHODS: Human MSCs were chondrogenically primed for 21 days, after which they were co-cultured with MSCs and HUVECs and cultured in endothelial growth medium for another 21 days. These aggregates were then implanted subcutaneously in nude rats for 4 weeks. We used a combination of bioluminescent imaging, microcomputed tomography, histology (Masson's trichrome and Alizarin Red) and immunohistochemistry (CD31, CD146, and alpha-smooth actin) to assess the vascularisation and mineralisation potential of these MSC aggregates in vivo. RESULTS: Pre-vascularised cartilaginous aggregates were found to have mature endogenous vessels (indicated by alpha-smooth muscle actin walls and erythrocytes) after 4 weeks subcutaneous implantation, and also viable human MSCs (detected by bioluminescent imaging) 21 days after subcutaneous implantation. In contrast, aggregates that were not pre-vascularised had no vessels within the aggregate interior and human MSCs did not remain viable beyond 14 days. Interestingly, the pre-vascularised cartilaginous aggregates were also the only group to have mineralised nodules within the cellular aggregates, whereas mineralisation occurred in the alginate surrounding the aggregates for all other groups. CONCLUSIONS: Taken together these results indicate that a combined chondrogenic priming and pre-vascularisation approach for in vitro culture of MSC aggregates shows enhanced vessel formation and increased mineralisation within the cellular aggregate when implanted subcutaneously in vivo. PMID- 26541818 TI - The natural dual cyclooxygenase and 5-lipoxygenase inhibitor flavocoxid is protective in EAE through effects on Th1/Th17 differentiation and macrophage/microglia activation. AB - Prostaglandins and leukotrienes, bioactive mediators generated by cyclooxygenases (COX) and 5-lipoxygenase (5-LO) from arachidonic acid, play an essential role in neuroinflammation. High levels of LTB4 and PGE2 and increased expression of COX and 5-LO, as well as high expression of PGE2 receptors were reported in multiple sclerosis (MS) patients and in experimental autoimmune encephalomyelitis (EAE). Prostaglandins and leukotrienes have an interdependent and compensatory role in EAE, which led to the concept of therapy using dual COX/5-LO inhibitors. The plant derived flavocoxid, a dual COX/5-LO inhibitor with anti-inflammatory and antioxidant properties, manufactured as a prescription pharmaconutrient, was reported to be neuroprotective in models of transient ischemic stroke and brain injury. The present study is the first report on prophylactic and therapeutic effects of flavocoxid in EAE. The beneficial effects correlate with reduced expression of proinflammatory cytokines and of COX2 and 5-LO in spinal cords and spleens of EAE mice. The protective mechanisms include: 1. reduction in expression of MHCII/costimulatory molecules and production of proinflammatory cytokines; 2. promotion of the M2 phenotype including IL-10 expression and release by macrophages and microglia; 3. inhibition of Th1 and Th17 differentiation through direct effects on T cells. The direct inhibitory effect on Th1/Th17 differentiation, and promoting the development of M2 macrophages and microglia, represent novel mechanisms for the flavocoxid anti-inflammatory activity. As a dual COX/5-LO inhibitor with antioxidant properties, flavocoxid might be useful as a potential therapeutic medical food agent in MS patients. PMID- 26541819 TI - Microglia regulate hippocampal neurogenesis during chronic neurodegeneration. AB - Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population. The selective inhibition of microglial proliferation caused a reduction in neurogenesis and a restoration of normal neuronal differentiation, supporting a pro-neurogenic role for microglia. Using a gene screening strategy, we identified TGFbeta as a molecule controlling the microglial pro-neurogenic response in chronic neurodegeneration, supported by loss-of-function mechanistic experiments. By the selective targeting of microglial proliferation we have been able to uncover a pro-neurogenic role for microglia in chronic neurodegeneration, suggesting promising therapeutic targets to normalise the neurogenic niche during neurodegeneration. PMID- 26541820 TI - Updated prevalence rates of overweight and obesity in 11- to 17-year-old adolescents in Germany. Results from the telephone-based KiGGS Wave 1 after correction for bias in self-reports. AB - BACKGROUND: The nationwide "German Health Interview and Examination Survey for Children and Adolescents" (KiGGS), conducted in 2003-2006, showed an increase in the prevalence rates of overweight and obesity compared to the early 1990s, indicating the need for regularly monitoring. Recently, a follow-up-KiGGS Wave 1 (2009-2012)-was carried out as a telephone-based survey, providing self-reported height and weight. Since self-reports lead to a bias in prevalence rates of weight status, a correction is needed. The aim of the present study is to obtain updated prevalence rates for overweight and obesity for 11- to 17-year olds living in Germany after correction for bias in self-reports. METHODS: In KiGGS Wave 1, self-reported height and weight were collected from 4948 adolescents during a telephone interview. Participants were also asked about their body perception. From a subsample of KiGGS Wave 1 participants, measurements for height and weight were collected in a physical examination. In order to correct prevalence rates derived from self-reports, weight status categories based on self-reported and measured height and weight were used to estimate a correction formula according to an established procedure under consideration of body perception. The correction procedure was applied and corrected rates were estimated. RESULTS: The corrected prevalence of overweight, including obesity, derived from KiGGS Wave 1, showed that the rate has not further increased compared to the KiGGS baseline survey (18.9 % vs. 18.8 % based on the German reference). CONCLUSION: The rates of overweight still remain at a high level. The results of KiGGS Wave 1 emphasise the significance of this health issue and the need for prevention of overweight and obesity in children and adolescents. PMID- 26541822 TI - Impact of intrafractional respiratory-induced prostate mobility on PTV size. AB - PURPOSE: Daily image-guided radiation therapy significantly reduces setup errors, but it does not minimize intrafractional target mobility; respiratory-induced target motion is one of the reasons for this. Therefore, the main aim of this study was to evaluate the impact of respiratory-induced prostate motion on the clinical target volume (CTV) margins. METHODS: The analysis comprised 50 videos stored in digital format and recorded in a group of 50 patients during image guided radiation therapy for prostate cancer. Fluoroscopy time was 10 seconds. Respiratory motion of the prostate in the anterior-posterior and lateral direction was assessed on the basis of a fiducial marker (GoldAnchor) implanted into the prostate before the treatment planning procedure. RESULTS: The average values and standard deviations of respiratory-induced prostate motion in the superior-inferior and left-right (lateral) directions were 2.6 +/- 2.1 mm and 0.7 +/- 0.7 mm, respectively. The CTV margins calculated according to the van Herk formula based on respiratory prostate motion were 8 mm in the superior-inferior direction and 2 mm in the lateral direction. CONCLUSIONS: Respiratory-induced prostate mobility during radiotherapy is significant especially in the superior inferior direction, and can thus induce a geographical error. This confirms the need for determining CTV margins for this type of respiratory-induced mobility. PMID- 26541823 TI - The legacy of a pioneer. PMID- 26541821 TI - Region-specific dendritic simplification induced by Abeta, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes. AB - BACKGROUND: Dendritic simplification, a key feature of the neurodegenerative triad of Alzheimer's disease (AD) in addition to spine changes and neuron loss, occurs in a region-specific manner. However, it is unknown how changes in dendritic complexity are mediated and how they relate to spine changes and neuron loss. RESULTS: To investigate the mechanisms of dendritic simplification in an authentic CNS environment we employed an ex vivo model, based on targeted expression of enhanced green fluorescent protein (EGFP)-tagged constructs in organotypic hippocampal slices of mice. Algorithm-based 3D reconstruction of whole neuron morphology in different hippocampal regions was performed on slices from APPSDL-transgenic and control animals. We demonstrate that induction of dendritic simplification requires the combined action of amyloid beta (Abeta) and human tau. Simplification is restricted to principal neurons of the CA1 region, recapitulating the region specificity in AD patients, and occurs at sites of Schaffer collateral input. We report that gamma-secretase inhibition and treatment with the NMDA-receptor antagonist, CPP, counteract dendritic simplification. The microtubule-stabilizing drug epothilone D (EpoD) induces simplification in control cultures per se. Similar morphological changes were induced by a phosphoblocking tau construct, which also increases microtubule stability. In fact, low nanomolar concentrations of naturally secreted Abeta decreased phosphorylation at S262 in a cellular model, a site which is known to directly modulate tau-microtubule interactions. CONCLUSIONS: The data provide evidence that dendritic simplification is mechanistically distinct from other neurodegenerative events and involves microtubule stabilization by dendritic tau, which becomes dephosphorylated at certain sites. They imply that treatments leading to an overall decrease of tau phosphorylation might have a negative impact on neuronal connectivity. PMID- 26541824 TI - NtGNL1a ARF-GEF acts in endocytosis in tobacco cells. AB - BACKGROUND: Processes of anterograde and retrograde membrane trafficking play an important role in cellular homeostasis and dynamic rearrangements of the plasma membrane (PM) in all eukaryotes. These processes depend on the activity of adenosine ribosylation factors (ARFs), a family of GTP-binding proteins and their guanine exchange factors (GEFs). However, knowledge on the function and specificity of individual ARF-GEFs for individual steps of membrane trafficking pathways is still limited in plants. RESULTS: In this work, treatments with various trafficking inhibitors showed that the endocytosis of FM 4-64 is largely dynamin-dependent and relies on proteins containing endocytic tyrosine-based internalization motif and intact cytoskeleton. Interestingly, brefeldin A (BFA), reported previously as an inhibitor of anterograde membrane trafficking in plants, appeared to be the most potent inhibitor of endocytosis in tobacco. In concert with this finding, we demonstrate that the point mutation in the Sec7 domain of the GNOM-LIKE protein1a (NtGNL1a) confers intracellular trafficking pathway-specific BFA resistance. The internalization of FM 4-64 and trafficking of PIN-FORMED1 (PIN1) auxin efflux carrier in BY-2 tobacco cells were studied to reveal the function of the ARF-GEF NtGNL1a in these. CONCLUSIONS: Altogether, our observations uncovered the role of NtGNL1a in endocytosis, including endocytosis of PM proteins (as PIN1 auxin efflux carrier). Moreover these data emphasize the need of careful evaluation of mode of action of non-native inhibitors in various species. In addition, they demonstrate the potential of tobacco BY-2 cells for selective mapping of ARF-GEF-regulated endomembrane trafficking pathways. PMID- 26541826 TI - Preparing Patients and Partners for Recovery From the Side Effects of Prostate Cancer Surgery: A Group Approach. AB - OBJECTIVE: To evaluate the acceptance and knowledge attained in a preoperative psychoeducational group seminar for patients and partners. Education before radical prostatectomy (RP) helps patients set appropriate expectations for functional recovery. We hypothesized that the seminar would be acceptable and would facilitate learning. MATERIALS AND METHODS: Men scheduled for RP from March 1, 2012, to July 31, 2013, were eligible, and partners were invited. The 2.5-hour interactive seminar included multidisciplinary presentations about surgery related urinary and sexual outcomes, rehabilitation, and couples' work toward recovering sexual intimacy. A satisfaction and knowledge survey was administered immediately afterward. We analyzed demographic and satisfaction data with descriptive statistics and evaluated congruence of patients' and partners' knowledge responses using nonparametric statistics. RESULTS: Of 618 patients scheduled, 426 patients and 342 partners attended; 323 couples provided complete data. Over 90% of participants found the seminar informative and 74% found a group setting comfortable; 84% found travel to the seminar burdensome. Most patients and partners (84% and 90%, respectively) expected some urinary incontinence and understood rehabilitation strategies to regain bladder control; 84% of patients and 78% of partners expected postsurgery sexual activity to be different and 73% of patients and 65% of partners expected surgery to make erections worse. Couples were incongruent regarding frequency of incontinence, likelihood of erectile dysfunction, and sex being different after surgery: patients were more realistic. CONCLUSION: A preoperative psychoeducational group seminar on the recovery from RP side effects promotes realistic expectations and is acceptable to patients and partners. Incongruent couples may need further instruction after surgery. Web-based methodology could improve access and should be studied in future research. PMID- 26541827 TI - WITHDRAWN: Editorial Comment on "Abnormal Expression of Sg I is Closely Related to Seminal Vesiculitis". AB - The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.urology.2015.08.052. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26541825 TI - DDX3, a potential target for cancer treatment. AB - RNA helicases are a large family of proteins with a distinct motif, referred to as the DEAD/H (Asp-Glu-Ala-Asp/His). The exact functions of all the human DEAD/H box proteins are unknown. However, it has been consistently demonstrated that these proteins are associated with several aspects of energy-dependent RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. In addition, DEAD/H box proteins participate in nuclear-cytoplasmic transport and organellar gene expression.A member of this RNA helicase family, DDX3, has been identified in a variety of cellular biogenesis processes, including cell-cycle regulation, cellular differentiation, cell survival, and apoptosis. In cancer, DDX3 expression has been evaluated in patient samples of breast, lung, colon, oral, and liver cancer. Both tumor suppressor and oncogenic functions have been attributed to DDX3 and are discussed in this review. In general, there is concordance with in vitro evidence to support the hypothesis that DDX3 is associated with an aggressive phenotype in human malignancies. Interestingly, very few cancer types harbor mutations in DDX3, which result in altered protein function rather than a loss of function.Efficacy of drugs to curtail cancer growth is hindered by adaptive responses that promote drug resistance, eventually leading to treatment failure. One way to circumvent development of resistant disease is to develop novel drugs that target over-expressed proteins involved in this adaptive response. Moreover, if the target gene is developmentally regulated, there is less of a possibility to abruptly accumulate mutations leading to drug resistance. In this regard, DDX3 could be a druggable target for cancer treatment. We present an overview of DDX3 biology and the currently available DDX3 inhibitors for cancer treatment. PMID- 26541828 TI - Fast lithium-ionic conduction in a new complex hydride-sulphide crystalline phase. AB - A new crystalline phase derived from a 90LiBH4:10P2S5 mixture displays high lithium-ionic conductivity of log(sigma/S cm(-1)) = -3.0 at 300 K. It is stable up to 473 K and has both a wide potential window of 0-5 V and favorable mechanical properties for battery assembly. Its incorporation into a bulk-type all-solid-state TiS2/InLi battery enabled repeated battery operation at 300 K. PMID- 26541829 TI - Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a "Superior" Slow Pathway: A Distinct Supraventricular Tachyarrhythmia. AB - BACKGROUND: The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. METHODS AND RESULTS: We studied 6 women and 2 men (age, 74 +/- 7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378 +/- 119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. CONCLUSIONS: sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation. PMID- 26541830 TI - Minimal or maximal surgery for esophageal cancer? PMID- 26541831 TI - Outcome after aortic valve replacement in children: A systematic review and meta analysis. AB - OBJECTIVE: Despite an increasing interest in pediatric aortic valve repair, aortic valve replacement in children may be unavoidable. The evidence on outcome after pediatric aortic valve replacement is limited and usually reported in small case series. This systematic review and meta-analysis aims to provide an overview of reported outcome of pediatric patients after aortic valve replacement. METHODS: A systematic literature search for publications reporting outcome after pediatric aortic valve replacement published between January 1990 and May 2015 was conducted. Studies written in English with a study size of more than 30 patients were included. RESULTS: Thirty-four publications reporting on 42 cohorts were included in this review: 26 concerning the Ross procedure (n = 2409), 13 concerning mechanical prosthesis aortic valve replacement (n = 696), and 3 concerning homograft aortic valve replacement (n = 224). There were no studies on bioprostheses that met our inclusion criteria. The pooled mean patient age was 9.4 years, 12.8 years, and 8.9 years for Ross, mechanical prosthesis, and homograft recipients, respectively. Pooled mean follow-up was 6.6 years. The Ross procedure was associated with lower early (4.20%; 95% confidence interval [CI], 3.37-5.22 vs 7.34%; 95% CI, 5.21-10.34 vs 12.82%; 95% CI, 8.91-18.46) and late mortality (0.64%/y; 95% CI, 0.49-0.84 vs 1.23%/y; 95% CI, 0.85-1.79 vs 1.59%/y; 95% CI, 1.03-2.46) compared with mechanical prosthesis aortic valve replacement and homograft aortic valve replacement, respectively. No significantly different aortic valve reoperation rates were observed between the Ross procedure and mechanical prosthesis aortic valve replacement (1.60%/y; 95% CI, 1.27-2.02 vs 1.07%/y; 95% CI, 0.68-1.68, respectively), whereas homograft aortic valve replacement was associated with significantly higher aortic valve reoperation rates (5.44%/y; 95% CI, 4.24-6.98). The Ross procedure-associated right ventricular outflow tract reoperation rate was 1.91% per year (95% CI, 1.50 2.44). CONCLUSIONS: This systematic review illustrates that all currently available aortic valve substitutes are associated with suboptimal results in children, reflecting the urgent need for reliable and durable repair techniques and innovative replacement solutions for this challenging group of patients. PMID- 26541832 TI - Minimally invasive mitral repair: The cost is the same, but what is the price? PMID- 26541833 TI - A prospective study of a modified pin-in-plaster technique for treatment of fractures of the distal radius. AB - OBJECTIVES: There are various pin-in-plaster methods for treating fractures of the distal radius. The purpose of this study is to introduce a modified technique of 'pin in plaster'. METHODS: Fifty-four patients with fractures of the distal radius were followed for one year post-operatively. Patients were excluded if they had type B fractures according to AO classification, multiple injuries or pathological fractures, and were treated more than seven days after injury. Range of movement and functional results were evaluated at three and six months and one and two years post-operatively. Radiographic parameters including radial inclination, tilt, and height, were measured pre- and post-operatively. RESULTS: The average radial tilt was 10.6 degrees of volar flexion and radial height was 10.2 mm at the sixth month post-operatively. Three cases of pin tract infection were recorded, all of which were treated successfully with oral antibiotics. There were no cases of pin loosening. A total of 73 patients underwent surgery, and three cases of radial nerve irritation were recorded at the time of cast removal. All radial nerve palsies resolved at the six-month follow-up. There were no cases of median nerve compression or carpal tunnel syndrome, and no cases of tendon injury. CONCLUSION: Our modified technique is effective to restore anatomic congruity and maintain reduction in fractures of the distal radius. Cite this article: Bone Joint Res 2015;4:176-180. PMID- 26541834 TI - Components of chicken egg white extract smaller than 3 kDa in size promote 293T cell proliferation. AB - We previously found that chicken egg white extract could promote cell survival and proliferation. In the present study, we further separated this extract into its components to identify those primarily responsible for promoting cell proliferation. Components of differing molecular weight were separated from chicken egg white extract by ultrafiltration and 293T cell cultures were supplemented with various concentrations. The effects on cell proliferation were subsequently determined by a CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit (Promega). We demonstrate that components from chicken egg white smaller than 3 kDa in size are able to function as active ingredients promoting cellular proliferation. This discovery may identify a new and convenient additive for cell culture media to promote cell growth and proliferation. PMID- 26541835 TI - Endurance training in patients with schizophrenia and healthy controls: differences and similarities. AB - The aims were to examine the feasibility of and adaptations to endurance training in persons diagnosed with schizophrenia and to address the question whether the principles and beneficial effects of endurance training established in the healthy population apply also to patients with schizophrenia. In this controlled interventional study, 22 patients with schizophrenia and 22 healthy controls performed a standardized aerobic endurance training on bicycle ergometers over 12 weeks. Another group of 21 patients with schizophrenia played table soccer. Endurance capacity was measured with incremental cycle ergometry before and after the intervention and 3 months later. A specific set of outcome parameters was defined. The training stimuli can be assumed to be similar in both endurance groups. Endurance capacity improved significantly in the endurance groups, but not in the table soccer group. Patients and healthy controls showed comparable adaptations to endurance training, as assessed by physical working capacity and maximal achieved power. Differences were found in changes of performance at a lactate concentration of 3 mmol/l. Endurance training was feasible and effective in both groups. The principles and types of training that are usually applied to healthy controls need to be verified in patients with schizophrenia. Nevertheless, patients benefited from endurance training in terms of improvement of endurance capacity and reduction in the baseline deficit in comparison with healthy controls. Therefore, endurance training should be implemented in future therapy programs. These programs need to pay special attention to the differences between patients with schizophrenia and healthy controls. PMID- 26541836 TI - [Management of uveomeningitis in internal medicine: Proposal for a diagnostic work-up]. AB - Uveomeningitis relates to an inflammatory state extending from iris and ciliary bodies to the choroid behind the eye. Because of a close contact between eye and brain, and barrier disruption, the inflammation can spread into the central nervous system (CNS). We review the clinical manifestations of uveitis, which are known to provide helpful clues to the diagnosis and describe the infectious, inflammatory, and neoplastic conditions classically associated with the uveomeningitis. Inflammatory or auto-immune diseases are probably the most common clinically recognized causes of uveomeningitis associated with a significant pleiocytosis. These entities often cause inflammation of various tissues in the body, including ocular structures and the meninges (i.e., sarcoidosis, Behcet's disease, and Vogt-Koyanagi-Harada syndrome). The association of an infectious uveitis with an acute or a chronic meningo-encephalitis is unusual but occasionally the eye examination may suggest an infectious etiology or even a specific organism responsible for an uveomeningitis. One should consider the diagnosis of primary ocular-CNS lymphoma in patients of 40 years of age or older with bilateral uveitis, especially with prominent vitritis, showing poor response to corticosteroid therapy. Finally, an algorithm for the diagnostic approach of uveomeningitis is proposed. PMID- 26541837 TI - [MiRNA-381 inhibits the invasion of renal carcinoma and ?the underlying mechanisms]. AB - OBJECTIVE: To determine the inhibitory effect of miRNA-381 on renal carcinoma invasion and to explore the underlying mechanisms.? METHODS: After up-regulation of miRNA-381, the inhibitory effect of miR-381 on cell invasion was investigated. We screened the target genes of miRNA-381 in a database (starBase) through combination of five programs including targetscan, picTar, RNA22, PITA and miRanda. Then, the predicted targeting genes were verified by the dual luciferase reporter assay. We also examined the expression of miRNA-381 and its target genes in renal cancer cells and tissues.? RESULTS: Transfection and up-regulation of miRNA-381 resulted in a significant decrease in trans-membrane cell numbers and the ability of renal cell invasion. Bioinformatics analysis showed that CREB binding protein (CBP), beta-catenin and lymphoid enhancer binding factor-1 (LEF 1) were the potential targets of miRNA-381. In the luciferase reporter gene system, co-transfection of miRNA-381 with the 3'UTR of wild-type target gene led to a significant decrease in luciferase activity. The expression of miRNA-381 was decreased in various renal cancer cells, and it was particularly lower in highly metastatic cell lines (786-OHM). On the contrary, the expression levels of miRNA 381 target genes (CBP, beta-catenin and LEF-1) were significantly increased in cells and tissues.? CONCLUSION: MiRNA-381 can inhibit cell invasion in renal cancer by block the function of CBP, beta-catenin and LEF-1. PMID- 26541838 TI - [MicroRNA-33a regulates the invasion of cervical cancer cells via targeting Twist1]. AB - OBJECTIVE: To examine the expression of Twist1 in cervical cancer and to explore its biological function in the progression of cervical cancer.? METHODS: The expressions of Twist1 in 32 cervical cancers and matched normal tissues were examined by immunohistochemistry (IHC). Cell invasive ability and the expression of invasion-related genes were determined in RNAi-based Twist1-silencing HeLa cells. The relationship between Twist1 and microRNA-33a (miR-33a) in cervical cancer was studied by Pearson correlation analysis, and the roles of miR-33a in regulation of Twist1 and cell invasiveness were studied.? RESULTS: The positive expression rate of Twist1 was 75.0% (24/32) and 21.9% (7/32) in the cervical cancer and the matched normal tissues, respectively, with significant difference between them (P<0.05). Twist1 shRNA significantly decreased the invasiveness of HeLa cells (P<0.05). Compared with the matched normal tissues, the expression of miR-33a was increased in the cervical cancer tissues, which was negatively correlated with Twist1 (r=-0.661, P<0.05). Overexpression of miR-33a could significantly suppress Twist1 expression as well as cell invasiveness (P<0.05).? CONCLUSION: Twist1 is critical for the invasiveness of cervical cancer cells; miR 33a, as a tumor suppressor gene, functions as an upstream regulator of Twist1 and is involved in the invasiveness of cervical cancer cell. PMID- 26541839 TI - [Effect of nano-realgar on proliferation and apoptosis of human cervical carcinoma cells]. AB - OBJECTIVE: To investigate the effect of nano-realgar on proliferation and apoptosis of cervical cancer cells.? METHODS: Different cervical cancer cell lines (Caski/HPV16+, adeno carcinoma; Hela/HPV18+, squmous carcinoma; C33A/HPV-, adeno carcinoma) were incubated with nano-realgar at different concentrations (5, 10, 20, 40 mg/L) for different times (24, 48, 72, 96 h). The morphology was observed under phase contrast microscope. The cell viability and apoptosis were examined by MTT and flow cytometry, respectively.? RESULTS: The inhibitory effect of nano-realgar on the proliferation of cervical cancer cells was in a dose dependent manner, with a range of inhibitory rate from 9.02% to 49.06%. Taking the group (20 mg/L) for an example, the inhibitory rates for Caski, Hela and C33A were 39.15%, 36.17% and 30.56%, respectively. The results of flow cytometry showed that the nano-realgar induced apoptosis in a concentration-dependent manner, with a range of apoptosis rate from 19.29% to 99.54%. Also taking the group (20 mg/L) for an example, the apoptosis rates for Caski, Hela and C33A were (60.43 +/- 2.88)%, (41.95 +/- 3.01)% and (43.49 +/- 2.19)%, respectively. High concentration of nano-realgar (20 or 40 mg/L) could induce block of Hela and Caski at G2/M stage.? CONCLUSION: Nano-realgar can inhibit the proliferation of different cervical carcinoma cell lines and can induce the cell apoptosis. The inhibitory effect on cell proliferation is strongest for Caski, followed by Hela and C33A. It can also induce G2/M stage block on HPV positive cervical cancer cells at high enough concentration. PMID- 26541840 TI - [Diagnosis of primary tracheobronchial amyloidosis by multiplanar reconstruction of the computed tomography combined with bronchoscope]. AB - OBJECTIVE: To summarize the specific CT characteristics and the endoscopic findings of primary tracheobronchial amyloidosis (PTBA) for improvement of the diagnostic accuracy.? METHODS: The imaging features of 6 patients with PTBA were analyzed by multiplanar reconstructed CT and the fiberoptic bronchoscope, and the pathology were summarized retrospectively.? RESULTS: All PTBA patients received bronchoscopic examination and the definite diagnosis were confirmed by positive staining with Congo red. PTBA presented diffuse thickening of major airway and lumen stenosis in various degrees with scattered hemorrhage of the mucous membrane under CT and bronchoscope, which was more obvious in low part of trachea, main bronchus and lobar bronchus. The mucosa of trachea and bilateral main bronchi were irregular and bumpy with jutting nodes in 5 patients, which was called "wavy path" pattern. Widely nodular or stripy calcifications of airway were found in 4 patients, which was considered as specific imaging features in PTBA and was involved bilateral main bronchi largely. There were obstructive atelectasis in 2 patients, and calcifications of hilus of lung with longitudinal diaphragm lymph nodes in 3 patients, but they were not specific. Ignoring the extensive circumferential thickening of large airway, "wavy path sign" and rail like calcification was mainly responsible for misdiagnosis of PTBA as endobronchial tuberculosis or other diseases.? CONCLUSION: Attentions to the specific imaging features on multiplanar CT and the endoscopic findings are the fundamentals to avoid the misdiagnosis of PTBA. PMID- 26541841 TI - [Value of acute renal injury associated biomarkers for patients in intensive care unit]. AB - OBJECTIVE: To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU).? METHODS: From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM 1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve.? RESULTS: A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively.? CONCLUSION: uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage. PMID- 26541842 TI - [Clinical observation on the combined therapy of sitagliptin with insulin for patients with brittle diabetes]. AB - OBJECTIVE: To observe the clinical efficacy of sitagliptin plus insulin on patients with brittle diabetes and to determine the effect of the combined therapy on glucagon secretion.? METHODS: This randomized, double-blinded and placebo-controlled trial included 30 patients with brittle diabetes. Participants were randomly assigned (1:1) to receive the treatment of either sitagliptin plus insulin or placebo plus insulin for 12 weeks. The blood glucose, hemoglobin A1c, insulin dose, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose dependent insulinotropic polypeptide (GIP) and other parameters were determined.? RESULTS: After 12 weeks of treatment, blood glucose was controlled better by sitagliptin plus insulin (P<0.01). The patients had significantly lower glucose variability indices, lower daily insulin requirement and hemoglobin A1c in the group of sitagliptin plus insulin (P<0.01). After steamed bun test, past-meal GLP 1 levels at 30 min were higher (P<0.01) while GIP levels were lower (P<0.01), with glucagon suppression in the sitagliptin plus insulin group. No significant change was observed at any time point in placebo plus insulin group.? CONCLUSION: Sitagliptin significantly decreases blood glucose level and blood glucose fluctuation, which may contribute to the ability of sitagliptin in decreasing glucagon secretion. PMID- 26541843 TI - [System evaluation on Ginkgo Biloba extract in the treatment of acute cerebral infarction]. AB - OBJECTIVE: To evaluate the effect and safety of Ginkgo Biloba extract on the treatment of acute cerebral infarction.? METHODS: The Database of Wanfang, China National Knowledge Infrastructure (CNKI) and VIPU were screened for literatures regarding Ginkgo Biloba extract in the treatment of acute cerebral infarction, including the clinical randomized controlled trials. Meta-analysis based on the Revman 4.2 system was performed.? RESULTS: Compared with the control group, treatment with Ginkgo Biloba extract enhanced efficacy in the treatment of acute cerebral infarction (OR: 1.60-5.53), which displayed an improved neural function defect score [WMD -3.12 (95%CI: -3.96- -2.28)].? CONCLUSION: Ginkgo Biloba extract is beneficial to the improvement of neurological function in patients with acute cerebral infarction and it is safe for patients. PMID- 26541844 TI - [Effect of underground work on cardiovascular system ?in coal miners]. AB - OBJECTIVE: To study the effect of underground work on cardiovascular system health in coal miners.? METHODS: Male coal miners, who received electrocardiographic examinations between June, 2013 and August, 2014 in Hunan Prevention and Treatment Institute for Occupational Diseases to exclude pneumoconiosis, were enrolled for this study (n=3 134). Miners with 2 years or more underground work experience were selected as the exposed group (n=2 370), while miners without underground work experience were selected as the control group (n=764). The prevalence of electrocardiographic abnormalities and the influential factors were compared between the 2 groups.? RESULTS: The prevalences of electrocardiographic abnormalities, hypertension, heart rate abnormalities and cardiovascular system abnormalities in the exposed group vs the control group were 37.6% vs 25.4%, 20.5% vs 13.4%, 5.7% vs 6.0%, 49.8% vs 35.2%, respectively. The cardiovascular system abnormalities were correlated with the underground work (OR=3.128, 95% CI: 1.969-4.970), the underground work experience (OR=1.205, 95% CI: 1.070-1.358) and the type of works (mining worker OR=1.820, 95% CI: 1.527 2.169; auxiliary worker OR=1.937, 95% CI: 1.511-2.482; other worker OR=3.291, 95%CI: 2.120-5.109).? CONCLUSION: Underground work may increase the prevalence of cardiovascular system abnormalities for coal miners. The longer the coal miners work in underground, the higher the risk of the cardiovascular system abnormalities they are. PMID- 26541845 TI - [Relationship between dietary vitamin C and Type 2 diabetes]. AB - OBJECTIVE: To examine the correlation between dietary vitamin C intake and Type 2 diabetes.? METHODS: A total of 5 168 participants from Xiangya Hospital, Central South University were randomly selected. According to the vitamin C intake, the participants were divided into 5 groups: a Q1 group (n=1 033), a Q2 group (n=1 034), a Q3 group (n=1 034), a Q4 group (n=1 034) and a Q5 group (n=1 033). They were also divided into a Type 2 diabetes group (n=502) and a non-diabetes group (n=4 666). The height, weight, and blood pressure were measured, and vitamin C intake and other dairy consumption were evaluated using a food frequency questionnaire and fasting plasma glucose (FPG). The analysis of variance (ANOVA), Chi-square test, Mann-Whitney U test and logistic regression model were used to analyze the relationship between dietary vitamin C and Type 2 diabetes.? RESULTS: The univariate analysis showed that there were significant differences in the vitamin C consumption in energy intake, activity level, dietary fiber intake, nutritional supplementation status, drinking or not drinking, education level among the different vitamin C intake groups (all P<0.05). There were also significant differences in age, sex, body mass index (BMI), smoking status and vitamin C intake between the Type 2 diabetes group and the non-diabetes group (all P<0.05). After the adjustment for age, gender, hypertension, energy intake or smoking status, the multiple logistic regression model found that the multivariable adjusted OR was 0.610 (95% CI 0.428-0.870) for ?the highest level of vitamin C intake (>154.78 mg/d) in comparison with the lowest level (<= 63.26 mg/d). The results suggested that the vitamin C intake was inversely associated with the Type 2 diabetes (r=-0.029, P<0.05).? CONCLUSION: There is a significant negative correlation between the dietary vitamin C intake and the risk of Type 2 diabetes. PMID- 26541846 TI - [Depression in patients with facial acne vulgaris and ?the influential factors]. AB - OBJECTIVE: To understand the influential factors for depression in patients with facial acne vulgaris and to provide scientific evidence for a comprehensive and systematic treatment for acne vulgaris.? METHODS: A total of 287 outpatients with facial acne vulgaris, who visited the dermatology of the Third Xiangya Hospital, were surveyed by Beck Depression Inventory (BDI). The data was collected by Epidata software (version 3.1) and processed by SPSS software package (version 18.0). The influential factors for the depression of outpatients with facial acne vulgaris were analyzed by multinomial logistic regression.? RESULTS: A total of 181 patients with facial acne vulgaris showed various degrees of depression (BDI score>=5) and the rate was 63.1%. The symptoms for depression included sad and pessimistic attitude as well as the decreased attention to others (social withdrawal). The influential factors for mild, moderate or severe depression were gender, the degree and the course of acne. Female patients were more likely to suffer mild, moderate or severe depression (OR=3.62, 2.63, respectively); the risk of depression in acne patients was increased with the increase in degree of the severity (OR=2.31, 4.51, respectively); the patients with the acne course more than a year were more likely to show mild depression than those with a course less than a year (OR=4.30, 7.44, respectively). The patients with acne course more than 3 years were more likely to show moderate or severe depression compared to those with a course less than a year (OR=3.60).? CONCLUSION: Most of facial acne patients show a different degree of depression. The acne course is longer in female patients. The more severe the acne vulgaris is, the more suffering of the depression is. Psychological care should be considered to improve the treatment and quality of life. PMID- 26541847 TI - [Free radial forearm flap for reconstruction of head and neck soft tissue defects after tumor resection]. AB - OBJECTIVE: To explore the clinical effect of the free radial forearm flap on repairing tissue defects and reconstructing functions after tumor resection.? METHODS: From January, 2003 to December, 2011, 70 patients, including 43 squamous cell carcinomas of tongue, 12 buccal cancers, 5 carcinomas of the soft palate, 4 basal cell carcinomas of external nose, 3 lower lip cancers, 2 upper lip cancers, and 1 posterior wall of hypopharynx carcinoma, with the soft tissue defects in the head and neck underwent reconstructive operations with the free radial forearm flap after the malignant tumor resection. The area of defects ranged from 5 cm * 4 cm to 14 cm * 8 cm with the process of diseases from 4 to 30 months. The technique for grafting the free radial forearm flap and the appearance at sites of the donor and recipient, and the influence on the anatomy and function in both local sites were analyzed.? RESULTS: In the 70 patients, only 1 case of flap appeared necrosis due to venous reflux obstacle, and the remaining (98.4 %) survived. During the follow-up for 12-36 months, one case of hypopharyngeal carcinoma died from distant metastasis a year later, 2 cases of tongue cancer died of cardiovascular accident. Morphology and function for the sites at donor and recipient were satisfactory.? CONCLUSION: Free radical forearm flap is a good choice for the repair and functional reconstruction for tissue defects after tumor resection. PMID- 26541848 TI - [Effect of T4 endoscopic thoracic sympathicotomy on life quality in patients with primary palmar hyperhidrosis]. AB - OBJECTIVE: To assess the quality of life in patients with primary palmar hyperhidrosis before and after T4 endoscopic thoracic sympathicotomy (ETS) using the modified rating scales system for life quality.? METHODS: Between June, 2009 and May, 2014, forty-eight patients with primary palmar hyperhidrosis received ETS at the thoracic level T4. Patients completed self assessment of life quality by the modified rating scales system before and after the surgery. Follow-up data including effectiveness of operation, patient satisfaction and life quality were obtained at 1 and 6 months after the surgery.? RESULTS: ETS at the thoracic level T4 was performed successfully for all cases. No mortality or serious complications were observed. No one needed thoracotomy in the period of surgery. Mild or moderate compensatory sweating was appeared in 38 cases (79.1%) or 1 case (2.1%), respectively. None severe case was observed after T4 ETS. About 97.9% of the patients were very satisfied with the result of the operation and no patient regretted the surgical procedure. All patients answered the quality of life (QoL) questionnaire and showed the improvement of QoL after the procedure (F=763.67, P<0.001).? CONCLUSION: Primary palmar hyperhidrosis led to the reduction of life quality. ETS at T4 level could reduce sweating production and improve QoL in patients with primary palmar hyperhidrosis. PMID- 26541849 TI - [Imaging manifestations and pathologic basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors]. AB - OBJECTIVE: To investigate the imaging manifestations of CT, MRI and pathological basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors.? METHODS: CT or MRI images and pathological features for hepatic capsular retraction syndrome were retrospectively analyzed in 50 patients with benign and malignant liver tumors. Picture archive and communication system (PACS) was used to observe and compare the morphology, size, width, depth, edge of the capsular retraction and the status of liquid under the liver capsule. The structure, differentiation and proliferation of the tumor were analyzed under the microscope.? RESULTS: There were malignant liver tumors in 44 patients and benign tumor in 6 patients. The smooth or rough for the edge of capsular retraction was significant difference between the benign tumors and the malignant tumors with three differentiated grades (all P<0.05). There were significant difference in the width and depth for capsule retraction with different amount of fibrous tissues (all P<0.05). The width and depth of capsule retraction were positively correlated to the size of the tumors (r=0.557, 0.309 respectively, both P<0.05).? CONCLUSION: Benign and malignant hepatic tumors may appear capsule retraction syndrome, but there are morphological differences between them. The differences are closely related with the lesion size, differentiated degree of tumor and fibrous tissue proliferation. PMID- 26541850 TI - [Relationship between main pulmonary artery diameter and process of chronic pulmonary disease]. AB - OBJECTIVE: To explore the relationship between main pulmonary artery diameter and process of chronic pulmonary disease.? METHODS: We retrospectively reviewed 9 cases without pulmonary diseases (control group) and 100 cases with chronic pulmonary diseases, which were divided into 3 groups: the simple chronic pulmonary disease (A group, 37 cases), the compensatory period of chronic cor pulmonale (B group, 20 cases) and the decompensatory period of chronic cor pulmonale (C group, 43 cases). Main pulmonary artery diameter (MPAD) was measured by chest CT. The differences of MPAD among these 4 groups were analyzed.? RESULTS: There was a strong positive correlation between pulmonary artery diameter and process of chronic pulmonary disease. Mean MPAD in the group C was higher than that in the group B (P<0.05), and mean MPAD in the group B was higher than that in the group A (P<0.05). Mean MPAD in control group was the smallest one among all groups (P<0.05).? CONCLUSION: Main pulmonary artery diameter could reflect the process of chronic pulmonary disease. PMID- 26541851 TI - [Analysis and discussion on the facet of the spinal column, spiral CT lock multiplanar reconstruction and ?3D reconstruction]. AB - OBJECTIVE: To investigate the imaging appearances and diagnostic value of axial CT scanning, spiral CT multiplanar reconstruction (MPR) and three-dimensional (3D) reconstruction in vertebral facet joints locking.? METHODS: A total of 31 cases of vertebral facet joints locking, with injuries in different parts, were recruited to explore their CT features, and to evaluate their advantages in diagnosis against each other.? RESULTS: Among the CT images of 31 cases with "Hamburger" sign in axial view, there were 21 cases of cervical spine and 10 cases of thoracolumbar segment; in vertical plane of MPR, "top to top" form was formed below the inferior and the superior articular process, accompanied by I degrees spondylolisthesis and inferior articular process tip fracture; 5 cases were unilateral locked cervical spine; none case for thoracolumbar segment. The inferior articular process was crossed with the superior articular process below and moved forward, formed "back to back" form, accompanied by II degrees -III degrees spondylolisthesis. 9 or 6 cases were bilateral or unilateral locking cervical spine, 10 cases were thoracolumbar segment, accompanied by teardrop fracture in the vertebral body below cervical spine. In coronal plane of MPR, inferior articular process showed ingression in different extent, and relied on the superior articular process below or locked in the articular fossa (21 cases for cervical spine); inferior articular process displayed upward displacement or appeared with the superior articular process at the same time, which meant joint structure disappearing thoracolumbar segment (10 cases). In 3D reconstruction, 31 cases displayed clearly in the spatial form of vertebral facet joints locking and the degree of spondylolisthesis of vertebral body.? CONCLUSION: MPR and 3D image were more clear and intuitive in vertebral facet joints locking comparing to axial CT scan image. Spiral CT MPR and 3D reconstruction contributed to the diagnosis of vertebral facet joints locking and the reduction of misdiagnoses rates. PMID- 26541852 TI - [Analysis of satisfactions for services among outpatients and inpatients at the age of equal to or more than 15 years old in Hunan province]. AB - OBJECTIVE: To evaluate the satisfaction of service for outpatient within two weeks and for inpatient service within a year in Hunan Province in 2013 and to analyze the influential factors.? METHODS: Using the data from the First Health Service Survey of Hunan Province, we evaluated the satisfactions for service in outpatients and inpatients based on the listed satisfaction indicators of the Fifth National Health Service Survey questionnaire. Weighted logistic regression was used to examine the influential factors for patients' satisfactions. SURVEYFREQ and SURVEYLOGISTIC procedures in SAS9.2 were used to conduct statistical analysis.? RESULTS: The overall satisfaction proportion was 73.85% (95% CI: 68.67%-79.03%) and 66.31% (95% CI: 61.28%-71.34%) for outpatients and inpatients, respectively. After adjusting the location, gender, age and household income, high degree of satisfaction for outpatients was associated with good patience and trust in medical personnel as well as the low medical costs, with the adjusted odds ratios of 3.64, 5.38 and 3.34, respectively; high degree of satisfaction for inpatients was associated with a good attitude from medical personnel to patients' questions, high patients' trust in medical personnel and low medical costs, with the adjusted odds ratios of 2.56, 4.69 and 4.35, respectively.? CONCLUSION: Most of outpatients and inpatients were satisfied with medical services in 2013 in Hunan province. High degree of satisfaction is associated with good attitude from medical personnel to patients' questions, good patience and trust in medical personnel, and low medical costs. PMID- 26541853 TI - [Progress in studies on the relationship between ?Dicer and ovarian tumor]. AB - MiRNAs are short, noncoding RNAs that modulate gene expression at the posttranscriptional level and induce the degradation of the mRNA transcript or the inhibition of protein translation. Dicer is an endoribonuclease in the RNase III family that is essential for the production of miRNAs. The abnormal expression of Dicer is frequently found in the occurrence and development process of many kinds of tumors, which is closely related to the treatment and prognosis of tumor. PMID- 26541854 TI - [Portopulmonary hypertension with recurrent syncope: ?a case report and review of literature]. AB - A case of portopulmonary hypertension characterized by repeated syncope was retrospectively analyzed. Intrahepatic or extrahepatic factor-induced portal hypertension complicated with metabolic disorder of vasoactive substances, vascular pressure, inflammation, etc. may result in systolic and diastolic dysfunction of pulmonary arteries and systemic hyperdynamic circulation, the long term effect of which can induce vascular remodeling and consequently, pulmonary hypertension. The pathogenic process is rather insidious. Pulmonary hypertension is clinically characterized by the raised average pulmonary artery pressure, normal pulmonary capillary wedge pressure and high pulmonary vascular resistance. Currently available therapeutic approaches include drug therapy targeting on pulmonary hypertension and liver transplantation. PMID- 26541855 TI - Osteoporosis treatment may benefit breast cancer patients. PMID- 26541856 TI - [Survey of pain after ambulatory surgery: An internet-based instrument]. AB - BACKGROUND AND AIM: Pain after surgery continues to be undermanaged. Studies and initiatives aiming to improve the management of postoperative pain are growing; however, most studies focus on inpatients and pain on the first day after surgery. The management of postoperative pain after ambulatory surgery and for several days thereafter is not yet a major focus. One reason is the low return rate of the questionnaires in the ambulatory sector. This article reports the development and feasibility of a web-based electronic data collection system to examine pain and pain-related outcome on predefined postoperative days after ambulatory surgery. MATERIAL AND METHODS: In this prospective pilot study 127 patients scheduled for ambulatory surgery were asked to participate in a survey to evaluate aspects related to pain after ambulatory surgery. The data survey was divided in (1) a preoperative, intraoperative and postoperative part and (2) a postoperative internet-based electronic questionnaire which was sent via e-mail link to the patient on days 1, 3 and 7 after surgery. A software was developed using a PHP-based platform to send e-mails and retrieve the data after web-based entries via a local browser. Feasibility, internet-based hitches and compliance were assessed by an additional telephone call after day 7. RESULTS: A total of 100 patients (50 female) between 18 and 71 years (mean 39.1 +/- 12.7 years) were included in the pilot study. Return rates of the electronic questionnaires were 86% (days 3 and 7) and 91% (day 1 after surgery). All 3 electronic questionnaires were answered by 82% of patients. Aspects influencing the return rate of questionnaires were work status but not age, gender, education level and preoperative pain. Telephone interviews were performed with 81 patients and revealed high operability of the internet-based survey without any major problems. CONCLUSION: The user-friendly feasibility and operability of this internet-based electronic data survey system explain the high compliance and return rate of electronic questionnaires by patients at home after ambulatory surgery. This survey tool therefore provides unique opportunities to evaluate and improve postoperative pain management after ambulatory surgery. PMID- 26541857 TI - Estimating the hCGbetacf in urine during pregnancy. AB - OBJECTIVE: Elevated urine concentrations of hCG beta core fragment (hCGbetacf) are known to cause false negative qualitative point-of-care hCG test results, but limited information is available regarding urine hCGbetacf. In this study, we evaluate the relationship between serum and urine hCG concentrations and the frequency of elevated urine hCGbetacf concentrations. DESIGN AND METHODS: Paired serum and urine specimens were obtained from 60 women at various stages of pregnancy and hCG was measured using the Abbott Architect and Roche Cobas e602 assays. Urine specimens with the greatest difference in urine hCG concentrations between these two instruments were tested using a qualitative point-of-care device and hCGbetacf was quantified using LC-MS/MS. RESULTS: Urine hCG concentrations were lower than serum and the magnitude of the difference depended on whether the hCG assay detected hCGbetacf. Elevated hCGbetacf concentrations (>280,000pmol/L) were observed in 12% of specimens from an unselected patient population. There was a significant correlation (r=0.97; p<0.0001) between the difference (Roche hCG-Abbott hCG) and the hCGbetacf concentration as measured by LC-MS/MS (Roche-Abbott difference IU/L=(hCGbetacf (pmol/L)*0.131+656)). CONCLUSIONS: A correlation exists between serum and urine hCG concentrations but this correlation is variable. hCGbetacf concentrations can be estimated using two automated assay reagent platforms that differ in their recognition of hCGbetacf. PMID- 26541858 TI - Chronic kidney disease and 10-year risk of cardiovascular death. AB - BACKGROUND: In recent clinical guidelines, individuals with chronic kidney disease are considered to have a similar 10-year absolute risk of cardiovascular death as individuals with diabetes or established cardiovascular disease. There is limited evidence to support this claim. METHODS: We investigated the 10-year risk for cardiovascular death in individuals with moderate or severe chronic kidney disease (glomerular filtration rate of 30-60 or <30 mL/min/1.73 m(2), respectively) in a cohort of primary care health check-ups in Stockholm, Sweden (n = 295,191, 46% women, 4290 cardiovascular deaths during 10 years follow-up). We also assessed the risk associated with diabetes or cardiovascular disease. The inclusion criteria, exposure, study outcome and follow-up period adhered strictly to the definitions of the European Society of Cardiology guidelines. RESULTS: The absolute 10-year risk of cardiovascular death was 3.9% and 14.0% in individuals with moderate and severe chronic kidney disease, respectively, but was substantially lower in women and in younger individuals. The risk in individuals with prevalent diabetes and cardiovascular disease was approximately two and three times higher compared to the risk estimate for moderate chronic kidney disease (hazard ratio (HR) 4.1, 95% confidence interval (CI) 3.8-4.5 and HR 6.2, 95% CI 5.7-6.7 vs. HR 2.3 95% CI 2.0-2.6, respectively) while the risk for individuals with severe chronic kidney disease appeared more congruent to that of diabetes and cardiovascular disease (HR 5.5, 95% CI 3.3-8.9). CONCLUSIONS: Although moderate chronic kidney disease is an independent predictor for an increased 10-year risk of cardiovascular death, only those with severe chronic kidney disease had similar risk to those with diabetes or cardiovascular disease. PMID- 26541859 TI - Predictors of suboptimal breastfeeding: an opportunity for public health interventions. AB - BACKGROUND: Sub-optimum breastfeeding significantly contributes to the global burden of disease. Our aim was to identify risk factors associated with suboptimal breastfeeding in Southern Croatia. METHODS: Between February 2008 and August 2009, 773 mother-infant pairs were recruited from University Hospital of Split Maternity Unit. Mothers were interviewed at birth, 3, 6, 12 and 24 months. RESULTS: Ninety-nine percent of mothers initiated breastfeeding but only 2.2% of them exclusively breastfed whilst in hospital. At 24 months, 4.1% of mothers were breastfeeding. Exclusive and any breastfeeding at 3 months was negatively associated with maternal education of 12 years or less, smoking during pregnancy, intention to use a pacifier and in-hospital formula supplementation. In addition, exclusive breastfeeding at 3 months was negatively associated with primiparity, antenatal course non-attendance and not receiving assistance with breastfeeding from hospital staff. Antenatal course non-attendance and discussing infant feeding with a health professional during pregnancy lowered the odds for any breastfeeding at 6 months. At 12 and 24 months, a lower level of education, antenatal course non-attendance and not receiving advice in hospital on feeding frequency was significantly associated with lower odds of breastfeeding. Additionally, intention to use a pacifier was found to be a negative predictor of breastfeeding at 12 months. CONCLUSIONS: Important modifiable risk factors found to be significantly associated with suboptimal breastfeeding include smoking during pregnancy, intention to use a pacifier, in-hospital formula supplementation, not receiving advice from hospital staff on normal feeding patterns, not receiving assistance with breastfeeding in hospital and antenatal course non-attendance. PMID- 26541860 TI - Making decisions about colorectal cancer screening. A qualitative study among citizens with lower educational attainment. AB - BACKGROUND: Few decision aids (DAs) have been developed to support an informed choice to citizens with lower educational attainment about colorectal cancer screening. The aim of this study was to identify information needs and preferences for formats and content in a DA for this group of citizens. METHODS: Four focus groups were conducted among Danish men and women aged 50-74 years with lower educational attainment. A semi-structured interview guide was developed to explore participants' perceptions about colorectal cancer screening and wishes for a DA. The interviews were transcribed and analysed using an ethnographic approach. RESULTS: The participants appreciated information about the causes, symptoms, incidence and mortality of colorectal cancer compared with other common cancers. The majority preferred the information to be presented in a clear and simple way with numbers and figures kept to a minimum. Values clarification exercises were not found useful. Receiving a screening kit to collect a sample of faeces along with the invitation letter was seen by the participants as a clear request from the health authorities to get screened. However, the overall message in the DA was perceived as ambiguous by the participants as it both recommended screening and seemed to disclaim responsibility for it. CONCLUSION: The results are relevant to a discussion of the delicate balance between participants' call for a clear recommendation, and the purpose of a DA to present options in a neutral and balanced way. This discussion is relevant beyond the group of citizens with lower educational attainment. PMID- 26541861 TI - Ethyl pyruvate ameliorates experimental colitis in mice by inhibiting the HMGB1 Th17 and Th1/Tc1 responses. AB - Ethyl pyruvate (EP), a simple lipophilic pyruvate ester, has demonstrated protective effects against murine colitis through inhibition the release of inflammatory factor high-mobility group protein box 1 (HMGB1). HMGB1 has been implicated in several autoimmune diseases by inducing Thl and Thl7 cells activation. This study was designed to investigate whether EP amelioration of murine colitis is related to the blocking of the HMGB1-Th17/Thl pathway. We induced murine colitis by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Ethyl pyruvate was injected intraperitoneally once a day for 7days. One week after intrarectal challenge with TNBS, HMGB1, IL-17 and IFN gamma protein levels were remarkably increased following severe colon inflammation. Meanwhile, excessive infiltration of Th17 cells in colonic tissues, and an upregulated proportion of Th17 and Th1/Tc1 cells in the spleen and mesenteric lymph nodes (MLN) were found in the TNBS-treated group compared to the control group. Treatment with the HMGB1 inhibitor EP not only remarkably improved colon pathological damage, but also significantly reduced the number of Th17 cells in the local tissues of the colitis-induced mice. Furthermore, the percentage of Th1/Tc1 and Th17 cells in the spleen and MLN, as well as levels of serum IFN-gamma and IL-17A, were all markedly decreased in the EP-treated group. Moreover, in vitro, our results showed that EP in a dose dependent manner inhibited HMGB1 release induced by LPS from CT26 cells (murine colon adenocarcinoma cell line). These results suggest that HMGB1 contributes to the development of murine colitis by promoting the Th17 and Th1/Tc1 responses, and that EP can significantly inhibit HMGB1-Th17 and Thl/Tc1 pathway activation, which may provide better protection to mice with TNBS-induced colitis. PMID- 26541862 TI - Editor's Choice - Treatment of Aortic Prosthesis Infections by Graft Removal and In Situ Replacement with Autologous Femoral Veins and Fascial Strengthening. AB - INTRODUCTION: Aortic prosthetic graft infection (AGI) is a major challenge in vascular surgery. Eradicating the infection requires prosthetic material removal, debridement, and lower limb revascularization. For the past 15 years, we have used femoral veins for aorto-iliac reconstruction and tensor fascia lata to strengthen the upper anastomosis. OBJECTIVE: The purpose of this single institution retrospective study is to present results regarding in situ replacement of infected aortic grafts with autologous femoral veins (FVs). METHODS: From October 2000 to March 2013, patients treated for AGI with graft removal and autologous FV reconstruction at Helsinki University Hospital were included. Primary outcome measures were 30 day mortality, long-term treatment related mortality, and re-infection rate. Secondary outcome measures were long term all cause mortality and event free survival (graft rupture, re-intervention, major amputation). RESULTS: During a 13 year period 55 patients (42 male, 13 female) were operated on using a venous neo-aorto-iliac system for AGI. The mean follow up was 32 months (1-157 months). The 30 day mortality rate was 9% (5) and overall treatment related mortality 18% (10). All cause mortality during follow up was 22 (40%) and overall Kaplan-Meier survival was 90.7% at 30 days, 81.5% at 1 year, and 59.3% at 5 years. Graft rupture occurred in three (5%) cases, two of which were caused by graft re-infection (4%). Four patients required major amputation, one of them on arrival and three (5%) during the post-operative period. Nine (16%) patients needed interventions for the vein graft, and two graft limbs occluded during follow up. CONCLUSION: In situ reconstruction for aortic graft infection with autologous FV presents acceptable rates of morbidity and mortality, and remains the treatment of choice for AGI at Helsinki University Hospital. PMID- 26541863 TI - Utility of Intra-operative Cone Beam Computed Tomography in Endovascular Treatment of Aorto-iliac Occlusive Disease. AB - OBJECTIVE: Endovascular treatment of aorto-iliac occlusive disease (AIOD) is well established, but to maintain long-term patency, secondary interventions are common. Multiple stents and iliac artery tortuosity often make it difficult to evaluate stent compression intra-operatively and this might be a cause for later failure. Completion angiography (CA) and pressure gradient (PG) measurement are often used to assess the final intra-operative result. The purpose of this study was to evaluate the role of intra-operative cone beam computed tomography (CBCT) to optimize the primary operation results. METHOD: Fifty-three patients (28 females) were enrolled in a prospective study. All patients underwent endovascular aorto-iliac revascularization. Final intra-operative results were evaluated with additional CBCT, after CA and PG were found to be satisfactory. Imaging findings and imaging based adjunctive procedures were recorded. RESULTS: One hundred and sixty five stents were placed because of AIOD. Twenty patients underwent adjunctive procedures after the primary stenting. In 24.5% (13/53) cases, adjunctive procedures were indicated solely by the CBCT findings, as both standard CA and PG were normal. Twenty-six of the 53 patients had kissing stents placed at the aortic bifurcation. Of the kissing stent patients, 34.6% required adjunctive procedures and in two thirds these stent compressions were detected only by CBCT. CONCLUSION: The use of CBCT revealed a significant number of stent compressions that were not found with CA and PG. When performing endovascular procedures at the aortic bifurcation, CBCT is an excellent intra-operative evaluation method to assess the configuration of deployed stents. In this study, CBCT improved the technical results intra-operatively, which might influence the long-term patency positively. PMID- 26541864 TI - Prediction of Lateral Pelvic Lymph-Node Metastasis in Low Rectal Cancer by Magnetic Resonance Imaging. AB - OBJECTIVE: This study was designed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for lateral pelvic lymph-node metastasis. PATIENTS: Eighty-four patients with primary lower rectal cancer were examined by MRI and subsequently underwent radical surgery with lateral pelvic lymph-node dissection, without preoperative treatment. Lateral lymph-node metastases were assessed preoperatively by MRI, and the results were compared with the histopathological findings. The criterion for lateral lymph-node metastasis was any recognizable lymph node in the pelvic wall, regardless of diameter. RESULT: Lateral pelvic lymph-node metastasis was diagnosed on preoperative MRI in 16 patients (19.9 %). The overall patient-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI were 75, 69.1, 36.4, 92.2, and 70.2 %, respectively. When a cut-off value of 10 mm was used for diagnosis, the corresponding values were 43.8, 98.5, 87.5, 88.1, and 88.1 %, respectively. The mean diameter of metastatic nodes (14.7 mm) was significantly larger than that of negative nodes (5.7 mm; P < 0.01). CONCLUSION: MRI is an effective technique for predicting lateral pelvic node involvement and thus may facilitate preoperative decision-making in rectal cancer treatment. A cut-off value of 10 mm is useful for avoiding unnecessary lateral lymph-node dissection. PMID- 26541865 TI - Long-Term Surveillance of Treated Hyperparathyroidism for Multiple Endocrine Neoplasia Type 1: Recurrence or Hypoparathyroidism? AB - BACKGROUND: Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is surgically treated with either a subtotal parathyroidectomy removing 3 or 3,5 glands (SPX), less than 3 glands (LSPX), or a total parathyroidectomy with autotransplantation (TPX). Previous studies with shorter follow-up have shown that LSPX and SPX are associated with recurrent HPT, and TPX with hypocalcemia and substitution therapy. We examined the situation after long term follow-up (median 20,6 years). METHODS: Sixty-nine patients with MEN1 HPT underwent 110 operations, the first operation being 31 LSPX, 30 SPX, and 8 TPX. Thirty patients underwent reoperative surgery in median 120 months later, as completion to TPX (n = 12), completion of LSPX to SPX (n = 9), extirpation of single glands (n = 3) still resulting in LSPX, and resection of forearm grafts (n = 3). Nine patients underwent a second, and 2 a third reoperation. In 24 patients genetic testing confirmed MEN1, and in the remaining heredity and phenotype led to the diagnosis. RESULTS: TPX had higher risk for hypoparathyroidism necessitating substitution therapy, at latest follow-up 50%, compared to SPX (16% after 3-6 months; none at latest follow-up). Recurrent HPT was common after LSPX, leading to 24 reoperations in 17 patients. No need for substitution therapy after SPX indicated forthcoming recurrent disease. Not having hypocalcemia in the postoperative period and less radical surgery than TPX were significantly associated to risk for recurrence. Further, mutation in exon 3 in the MEN1 gene may eventually be linked to risk of recurrence. CONCLUSION: LSPX is highly associated with recurrence and TPX with continuous hypoparathyroidism, also after long-term follow-up. SPX should be the chosen method in the majority of patients with MEN1 HPT. PMID- 26541866 TI - Use of 3D Prototypes for Complex Surgical Oncologic Cases. AB - INTRODUCTION: Physical 3D models known by the industry as rapid prototyping involve the creation of a physical model from a 3D computer version. In recent years, there has been an increasing number of reports on the use of 3D models in medicine. Printing such 3D models with different materials integrating the many components of human anatomy is technically challenging. In this article, we report our technological developments along with our clinical implementation experience using high-fidelity 3D prototypes of tumors encasing major vessels in anatomically sensitive areas. METHODS: Three patients with tumors encasing major vessels that implied complex surgery were selected for surgical planning using 3D prototypes. 3D virtual models were obtained from routine CT and MRI images. The models, with all their anatomical relations, were created by an expert pediatric radiologist and a surgeon, image by image, along with a computerized-aided design engineer. RESULTS: Surgeons had the opportunity to practice on the model before the surgery. This allowed questions regarding surgical approach; feasibility and potential complications to be raised in advance of the actual procedure. All patients then successfully underwent surgery as planned. CONCLUSION: Having a tumor physically printed in its different main component parts with its anatomical relationships is technically feasible. Since a gross total resection is prognostic in a significant percentage of tumor types, refinements in planning may help achieve greater and safer resections therefore contributing to improve surgical management of complex tumors. In this early experience, 3D prototyping helped significantly in the many aspects of surgical oncology planning. PMID- 26541867 TI - Pathologic Assessment of Pancreatic Fibrosis in Predicting Pancreatic Fistula and Management of Prophylactic Drain Removal After Pancreaticoduodenectomy. PMID- 26541868 TI - The Characteristics of Bone Metastasis in Patients with Colorectal Cancer: A Long Term Report from a Single Institution. AB - BACKGROUND: Bone metastasis in patients with colorectal cancer (CRC) is very rare, and data are extremely lacking. We aimed to evaluate the characteristics of bone metastasis in patients with CRC. MATERIALS AND METHODS: We performed a chart review of 63 patients (1.1 %) with bone metastasis among 5479 patients who underwent surgery for CRC. RESULTS: Most patients were stage 3 (17.5 %) or 4 (73.0 %), and 32 patients (50.8 %) were diagnosed with bone metastasis at initial diagnoses of CRC. Thirty-one patients developed bone metastasis during the follow up period with median 10.1-month interval. PET-CT was most frequently used for the diagnosis of bone metastasis (71.4 %), and the spine was the most commonly involved site (77.8 %). Most patients had multiple bone metastases (73.0 %) and other metastases (87.3 %). Bone pain was the most common skeletal-related event (25.4 %), and patients were treated with radiation (25.4 %), surgery (14.3 %), or bisphosphonate (6.3 %). The median survival time was 17.8 months, and the 5-year survival rate was 5.7 %. In the multivariate analysis, the risk factors for survival included initial bone metastasis (hazard ratio [HR] 3.03; P < 0.001) and bone metastasis from colon cancer (HR 1.87; P = 0.04). CONCLUSION: Bone metastasis in patients with CRC is extremely rare and shows poor prognosis. PMID- 26541869 TI - Fatal Cases of Bloodstream Infection by Fusarium solani and Review of Published Literature. AB - Fusarium species are ubiquitously present in environment and are well known as human pathogens with high mortality rate in immunocompromised patients. We report here two cases where immunocompromised patients developed fatal bloodstream infections by this organism. Isolates were further identified by ITS1 region sequencing which confirmed them as Fusarium solani. Antifungal susceptibility testing was done following CLSI M38-A2 guidelines to amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and micafungin. Both patients had a fatal outcome and expired of septic shock. Therefore, identification up to species level is of utmost importance as that helps in directing the management of the patient thereby leading to a favourable outcome. PMID- 26541870 TI - A comprehensive study of sensorimotor cortex excitability in chronic cocaine users: Integrating TMS and functional MRI data. AB - BACKGROUND: Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS). METHODS: A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MRI data were acquired from a subset of 28 individuals who performed a block-design finger tapping task. RESULTS: TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhibition. Task-evoked BOLD signal in the motor cortex was significantly correlated with ICF in the cocaine users. There was no significant difference in brain-skull distance between groups. CONCLUSION: These data demonstrated that cocaine users have disrupted cortical facilitation (as measured with TMS), which is related to elevated BOLD signal. Cortical inhibition, however, is largely intact. Given the relationship between ICF and glutamatergic agents, this may be a potentially fruitful and treatable target in addiction. Finally, among controls the distance from the scalp to the cortex was correlated with the motor threshold which may be a useful parameter to integrate into therapeutic TMS protocols in the future. PMID- 26541871 TI - Reduction in sphingosine kinase 1 influences the susceptibility to dengue virus infection by altering antiviral responses. AB - Sphingosine kinase (SK) 1 is a host kinase that enhances some viral infections. Here we investigated the ability of SK1 to modulate dengue virus (DENV) infection in vitro. Overexpression of SK1 did not alter DENV infection; however, targeting SK1 through chemical inhibition resulted in reduced DENV RNA and infectious virus release. DENV infection of SK1-/ - murine embryonic fibroblasts (MEFs) resulted in inhibition of infection in an immortalized line (iMEF) but enhanced infection in primary MEFs (1 degrees MEFs). Global cellular gene expression profiles showed expected innate immune mRNA changes in DENV-infected WT but no induction of these responses in SK1-/- iMEFs. Reverse transciption PCR demonstrated a low-level induction of IFN-beta and poor induction of mRNA for the interferon-stimulated genes (ISGs) viperin, IFIT1 and CXCL10 in DENV-infected SK1-/- compared with WT iMEFs. Similarly, reduced induction of ISGs was observed in SK1-/- 1 degrees MEFs, even in the face of high-level DENV replication. In both iMEFs and 1 degrees MEFs, DENV infection induced production of IFN-beta protein. Additionally, higher basal levels of antiviral factors (IRF7, CXCL10 and OAS1) were observed in uninfected SK1-/- iMEFs but not 1 degrees MEFs. This suggests that, in this single iMEF line, lack of SK1 upregulates the basal levels of factors that may protect cells against DENV infection. More importantly, regardless of the levels of DENV replication, all cells that lacked SK1 produced IFN-beta but were refractory to induction of ISGs such as viperin, IFIT1 and CXCL10. Based on these findings, we propose new roles for SK1 in affecting innate responses that regulate susceptibility to DENV infection. PMID- 26541872 TI - An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities. AB - An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development. PMID- 26541873 TI - What do we really know about the impacts of one of the 100 worst invaders in Europe? A reality check. AB - Invasive species are one of the greatest threats to biodiversity worldwide, and to successfully manage their introductions is a major challenge for society. Knowledge on the impacts of an invasive species is essential for motivating decision makers and optimally allocating management resources. We use a prominent invasive fish species, the round goby (Neogobius melanostomus) to objectively quantify the state of scientific knowledge on its impacts. Focusing on how native fish species are affected by round goby invasions, we analyzed 113 peer-reviewed papers and found that impacts are highly ecosystem and time scale dependent. We discovered round goby impacts to be profound, but surprisingly complex. Even if identical native species were affected, the impacts remained less comparable across ecosystems than expected. Acknowledging the breadth but also limitations in scientific knowledge on round goby impacts would greatly improve scientists' ability to conduct further research and inform management measures. PMID- 26541874 TI - Improving invasive species management by integrating priorities and contributions of scientists and decision makers. AB - Managing invasive species is a major challenge for society. In the case of newly established invaders, rapid action is key for a successful management. Here, we develop, describe and recommend a three-step transdisciplinary process (the "butterfly model") to rapidly initiate action for invasion management. In the framing of a case study, we present results from the first of these steps: assessing priorities and contributions of both scientists and decision makers. Both scientists and decision makers prioritise research on prevention. The available scientific knowledge contributions, however, are publications on impacts rather than prevention of the invasive species. The contribution of scientific knowledge does thus not reflect scientists' perception of what is essentially needed. We argue that a more objective assessment and transparent communication of not only decision makers' but also scientists' priorities is an essential basis for a successful cooperation. Our three-step model can help achieve objectivity via transdisciplinary communication. PMID- 26541875 TI - ED breast cases and other breast emergencies. AB - Patients with pathologic processes of the breast commonly present in the Emergency Department (ED). Familiarity with the imaging and management of the most common entities is essential for the radiologist. Additionally, it is important to understand the limitations of ED imaging and management in the acute setting and to recognize when referrals to a specialty breast center are necessary. The goal of this article is to review the clinical presentations, pathophysiology, imaging, and management of emergency breast cases and common breast pathology seen in the ED. PMID- 26541876 TI - Electron transfer from the A1A and A1B sites to a tethered Pt nanoparticle requires the FeS clusters for suppression of the recombination channel. AB - In this work, a previously described model of electron withdrawal from the A1A/A1B sites of Photosystem I (PS I) was tested using a dihydrogen-producing PS I-NQ(CH2)15S-Pt nanoconstruct. According to this model, the rate of electron transfer from A1A/A1B to a tethered Pt nanoparticle is kinetically unfavorable relative to the rate of forward electron transfer to the FeS clusters. Dihydrogen is produced only when an external donor rapidly reduces P700(+), thereby suppressing the recombination channel and allowing the electron in the FeS clusters to proceed via uphill electron transfer through the A1A/A1B quinones to the Pt nanoparticle. We tested this model by sequentially removing the FeS clusters, FB, FA, and FX, and determining the concentration of cytochrome c6 (Cyt c6) at which the backreaction was outcompeted and dihydrogen production was observed. P700-FA cores were generated in a menB insertionally inactivated strain by removing FB with HgCl2; P700-FX cores were generated in a menB psaC insertionally inactivated strain that lacks FA and FB, and P700-A1 cores were generated in a menB rubA insertionally inactivated strain that lacks FX, FA and FB. Quinone incorporation was measured using transient electron paramagnetic resonance spectroscopy and time resolved optical spectroscopy. Cyt c6 was titrated into each of these PS I preparations and the kinetics of P700(+) reduction were measured. A similar experiment was carried out on PS I-NQ(CH2)15S Pt nanoconstructs assembled from these PS I preparations. This study showed that the concentration of Cyt c6 needed to produce dihydrogen was comparable to that needed to suppress the backreaction. We conclude that the FeS clusters serve to 'park' the electron and thereby extend the duration of the charge-separated state; however, in doing so, the redox advantage of removing the electron at A1A/A1B is lost. PMID- 26541877 TI - Robust Cluster Building Unit: Icosanuclear Heteropolyoxocopperate Templated by Carbonate. AB - The encapsulation of carbonate derived from atmospheric CO2 has resulted in an icosanuclear heteropolyoxocopperate, isolated as a metal-organic 1D chain, 2D sheet, or 3D framework, in which the Cu20 nanocluster represents the first eight capped alpha-Keggin polyoxometalate with the late-transition-metal Cu(II) as the polyatom, CO3(2-) as the heteroanion, and OH(-) and suc(2-) or glu(2-) (H2suc=succinic acid; H2glu=glutaric acid) as the terminal ligands, which suggests a conceptual similarity to classical polyoxometalates. Even in the presence of competitive SO4(2-) in the assembly system, the CO3(2-) anion is still captured as a template to direct the formation of the Cu20 nanocluster, which indicates the stronger templation ability of CO3(2-) compared with SO4(2-). When other aliphatic dicarboxylates, such as glutaric acid, were used as ligands, the CO3(2-)-templated Cu20 nanocluster was maintained and acted as a cluster building unit (CBU) to be linked by two glutarate bridges to generate a distinct 1D metal-organic chain. This report presents not only a rare example of a huge anion-templated transition-metal cluster, but also its use as a robust CBU to construct novel coordination architectures. Variable-temperature magnetic susceptibility studies revealed that an antiferromagnetic interaction exists within the Cu20 nanocluster. The correlation between the coordination structure and the electron paramagnetic resonance spectra recorded of both powder and single-crystal samples are discussed in detail. PMID- 26541878 TI - Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial. AB - BACKGROUND: Acute diarrhoea is a frequent health problem in both travellers and residents that has a social and economic impact. This study compared the efficacy and tolerability of two loperamide-simeticone formulations and a Saccharomyces boulardii capsule as symptomatic treatment. METHODS: This was a prospective, randomised, single (investigator)-blind, three-arm, parallel group, non inferiority clinical trial in adult subjects with acute diarrhoea at clinics in Mexico and India, with allocation to a loperamide-simeticone 2/125 mg caplet or chewable tablet (maximum eight in 48 h) or S. boulardii (250 mg twice daily for 5 days). OUTCOME MEASURES: The primary outcome measure was the number of unformed stools between 0 and 24 h following the initial dose of study medication (NUS 0 24). The secondary outcome measures were time to last unformed stool (TLUS), time to complete relief of diarrhoea (TCRD), time to complete relief of abdominal discomfort (TCRAD) and the subject's evaluation of treatment effectiveness. Follow-up endpoints at 7 days were feeling of complete wellness; stool passed since final study visit; and continued or recurrent diarrhoea. SUBJECTS: In this study, 415 subjects were randomised to either a loperamide-simeticone caplet (n = 139), loperamide-simeticone chewable tablet (n = 139) or S. boulardii capsule (n = 137) and were included in the intention-to-treat analysis. RESULTS: With regards to mean NUS 0-24, the loperamide-simeticone caplet was non-inferior to loperamide-simeticone tablets (3.4 vs. 3.3; one-sided 97.5 % confidence interval <=0.5), with both significantly lower than S. boulardii (4.3; p < 0.001). The loperamide-simeticone groups had a shorter median TLUS [14.9 and 14.0 vs. 28.5 h (loperamide-simeticone caplet and chewable tablet groups, respectively, vs. S. boulardii); p < 0.001], TCRD (26.0 and 26.0 vs. 45.8 h; p < 0.001) and TCRAD (12.2 and 12.0 vs. 23.9 h; p < 0.005) than S. boulardii. Treatment effectiveness for overall illness, diarrhoea and abdominal discomfort relief was greater (p < 0.001) in the loperamide-simeticone groups than with S. boulardii. At 7-day follow-up most subjects reported passing stool at least once since the final study visit (loperamide-simeticone caplet 94.1 %, loperamide-simeticone chewable tablet 94.8 %, S. boulardii 97.0 %), did not experience continued or recurrent diarrhoea [loperamide-simeticone caplet 3.7 % (p < 0.03 vs. S. boulardii), loperamide-simeticone chewable tablet 3.7 %, S. boulardii 5.7 %] and felt completely well [loperamide-simeticone caplet 96.3 % (p < 0.02 vs. S. boulardii), loperamide-simeticone chewable tablet 96.3 % (p < 0.02 vs. S. boulardii), S. boulardii 88.6 %]. All treatments were well-tolerated with few adverse events. CONCLUSIONS: The loperamide-simeticone caplet was non-inferior to the original loperamide-simeticone chewable tablet formulation; both formulations can be expected to demonstrate similar clinical efficacy in the relief of symptoms of acute diarrhoea. Both loperamide-simeticone formulations were superior to the S. boulardii capsule in the primary and secondary endpoints. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00807326. PMID- 26541879 TI - James P. Allison Receives the 2015 Lasker-Debakey Award in Clinical Medical Research. PMID- 26541880 TI - Reducing Toxicity of Immune Therapy Using Aptamer-Targeted Drug Delivery. AB - Modulating the function of immune receptors with antibodies is ushering in a new era in cancer immunotherapy. With the notable exception of PD-1 blockade used as monotherapy, immune modulation can be associated with significant toxicities that are expected to escalate with the development of increasingly potent immune therapies. A general way to reduce toxicity is to target immune potentiating drugs to the tumor or immune cells of the patient. This Crossroads article discusses a new class of nucleic acid-based immune-modulatory drugs that are targeted to the tumor or to the immune system by conjugation to oligonucleotide aptamer ligands. Cell-free chemically synthesized short oligonucleotide aptamers represent a novel and emerging platform technology for generating ligands with desired specificity that offer exceptional versatility and feasibility in terms of development, manufacture, and conjugation to an oligonucleotide cargo. In proof-of-concept studies, aptamer ligands were used to target immune-modulatory siRNAs or aptamers to induce neoantigens in the tumor cells, limit costimulation to the tumor lesion, or enhance the persistence of vaccine-induced immunity. Using increasingly relevant murine models, the aptamer-targeted immune-modulatory drugs engendered protective antitumor immunity that was superior to that of current "gold-standard" therapies in terms of efficacy and lack of toxicity or reduced toxicity. To overcome immune exhaustion aptamer-targeted siRNA conjugates could be used to downregulate intracellular mediators of exhaustion that integrate signals from multiple inhibitory receptors. Recent advances in aptamer development and second-generation aptamer-drug conjugates suggest that we have only scratched the surface. PMID- 26541881 TI - In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011-2014. AB - Oritavancin is a lipoglycopeptide that has been approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) caused by susceptible organisms. Oritavancin causes cell death by inhibiting cell wall synthesis as well as depolarising and permeabilising the cellular membrane of Gram-positive pathogens. The activities of oritavancin in comparison with vancomycin, daptomycin and linezolid were determined against a collection of over 11000 recent clinical Gram-positive isolates from patient infections (2011-2014), including skin and skin-structure infections. A total of 7253 Staphylococcus aureus, 839 coagulase-negative staphylococci (CoNS), 1464 enterococci and 1637 beta-haemolytic streptococci (betaHS) were collected from the USA and Europe. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, and susceptibility was determined using CLSI and US Food and Drug Administration (FDA) (for oritavancin) breakpoint criteria. Equivalent in vitro activity (MIC50/90, 0.015-0.03/0.06 MUg/mL) was observed for oritavancin against meticillin-resistant S. aureus (MRSA), meticillin-susceptible S. aureus (MSSA) and Enterococcus faecalis in both regions. Slightly higher oritavancin MICs were obtained against CoNS, Streptococcus agalactiae, Enterococcus faecium (MIC90, 0.12 MUg/mL) and against other betaHS (MIC90, 0.25 MUg/mL). Oritavancin demonstrated comparatively lower MICs than daptomycin and vancomycin when tested against multidrug-resistant S. aureus, vancomycin-resistant enterococci and erythromycin-resistant betaHS. Oritavancin exhibited potent in vitro activity against the most common pathogens associated with ABSSSIs in the USA and Europe. PMID- 26541882 TI - Effectiveness of the addition of the brain region to the FDG-PET/CT imaging area in patients with suspected or diagnosed lung cancer. AB - PURPOSE: We aimed to evaluate the effectiveness of the brain region imaging in FDG-PET/CT scanning of patients with suspected or diagnosed lung cancer. MATERIALS AND METHODS: We performed the study retrospectively on the medical charts of 427 patients. We divided the FDG-PET/CT field of view (FOV) into four major imaging regions: brain, head-neck, abdomen and pelvis. Metastatic findings on these regions were checked and determined the potential of these findings to affect the chemotherapy or radiotherapy protocol or surgical management. If metastatic findings had a potential to modify these parameters, we named this situation as "clinical contribution". Considering the number of bed positions of these regions, we calculated the clinical contribution of each region and named as "effective clinical contribution". Then, we calculated the metastatic findings, clinical contribution, and effective clinical contribution ratios. RESULTS: We found different brain metastasis ratios for lung cancer, solitary pulmonary mass (SPM), and solitary pulmonary nodule (SPN) groups (8.7, 2.8 and 0.9 %, respectively). In addition, the clinical contribution and effective clinical contribution ratios in the brain region for these three groups were 6.4, 2.8, 0.0 and 6.4, 2.8, 0.0 %, respectively. The highest metastatic findings (30.6 %) and clinical contribution (9.8 %) ratios were found in the abdomen region of the lung cancer group. However, the highest effective clinical contribution ratio (6.8 %) was found in the brain region within the same group. CONCLUSIONS: The addition of the brain region to the limited whole-body FOV in FDG-PET/CT scanning seems to be effective in the lung cancer and SPM groups, but not in the SPN group. PMID- 26541884 TI - NRF2 Mediates Neuroblastoma Proliferation and Resistance to Retinoic Acid Cytotoxicity in a Model of In Vitro Neuronal Differentiation. AB - Retinoic acid (RA) morphogenetic properties have been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells' proliferation rate and increased cells' sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated nuclear factor erythroid 2-like factor 2 (NRF2) activation by RA. None of these effects were obtained with Trolox(r) as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of the ERK 1/2 and PI3K/AKT pathways revealed to be equally required to promote NRF2 activation and necessary for RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments; thus, this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols. PMID- 26541883 TI - Role of Matrix Metalloproteinases in the Pathogenesis of Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Studies revealed that the pathogenesis of TBI involves upregulation of MMPs. MMPs form a large family of closely related zinc-dependent endopeptidases, which are primarily responsible for the dynamic remodulation of the extracellular matrix (ECM). Thus, they are involved in several normal physiological processes like growth, development, and wound healing. During pathophysiological conditions, MMPs proteolytically degrade various components of ECM and tight junction (TJ) proteins of BBB and cause BBB disruption. Impairment of BBB causes leakiness of the blood from circulation to brain parenchyma that leads to microhemorrhage and edema. Further, MMPs dysregulate various normal physiological processes like angiogenesis and neurogenesis, and also they participate in the inflammatory and apoptotic cascades by inducing or regulating the specific mediators and their receptors. In this review, we explore the roles of MMPs in various physiological/pathophysiological processes associated with neurological complications, with special emphasis on TBI. PMID- 26541885 TI - Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy. AB - Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24 h, while the other, non-supplemented, were used as a control. All cultures were processed immunocytochemically for detection of the synaptic marker synaptophysin. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the prehypoxic level. Additionally, synaptic vulnerability was selective: large- and small-sized neurons were more susceptible to synaptic damage than the medium sized ones. Ghrelin treatment significantly increased the synapse density, as compared with the non-treated controls or with the prehypoxic period. The effect was detected in all neuronal subtypes. In conclusion, exogenous ghrelin has a robust impact on the recovery of cortical synapses after hypoxia. It raises the possibility that ghrelin or its analogs may have a therapeutic potential for treatment of postanoxic encephalopathy. PMID- 26541887 TI - Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families. AB - Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies. PMID- 26541889 TI - Novel application of the Sonopet for endoscopic posterior split and cartilage graft laryngoplasty. PMID- 26541888 TI - The effect of encapsulated glutamine on gut peptide secretion in human volunteers. AB - CONTEXT: Weight loss and improved blood glucose control after bariatric surgery have been attributed in part to increased ileal nutrient delivery with enhanced release of glucagon-like peptide 1 (GLP-1). Non-surgical strategies to manage obesity are required. The aim of the current study was to assess whether encapsulated glutamine, targeted to the ileum, could increase GLP-1 secretion, improve glucose tolerance or reduce meal size. METHODS: A single-center, randomised, double blind, placebo-controlled, cross-over study was performed in 24 healthy volunteers and 8 patients with type 2 diabetes. Fasting participants received a single dose of encapsulated ileal-release glutamine (3.6 or 6.0 g) or placebo per visit with blood sampling at baseline and for 4h thereafter. Glucose tolerance and meal size were studied using a 75 g oral glucose tolerance test and ad libitum meal respectively. RESULTS: In healthy volunteers, ingestion of 6.0 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 10.6 pg/ml vs 6.9 pg/ml, p=0.004), increased insulin concentrations after 90 min (mean 70.9 vs 48.5, p=0.048), and increased meal size at 120 min (mean 542 g eaten vs 481 g, p=0.008). Ingestion of 6.0 g glutamine was not associated with significant differences in GLP-1, glucose or insulin concentrations after a glucose tolerance test in healthy or type 2 diabetic participants. CONCLUSIONS: Single oral dosing of encapsulated glutamine did not provoke consistent increases in GLP-1 and insulin secretion and was not associated with beneficial metabolic effects in healthy volunteers or patients with type 2 diabetes. PMID- 26541890 TI - Self-efficacy versus perceived enjoyment as predictors of physical activity behaviour. AB - OBJECTIVE: Self-efficacy and physical activity (PA) enjoyment are related to PA behaviour, but it is unclear which is more important and how they interrelate. The purpose of this study was to examine how these two constructs interrelate to influence PA behaviour. DESIGN: Participants were low-active adults (n = 448) participating in a RCT examining the effect of a PA promotion intervention. Participants completed physical activity, enjoyment and self-efficacy measures at baseline, six and 12 months. RESULTS: Self-efficacy and enjoyment at both baseline and six months predicted PA at 12 months. However, enjoyment was a stronger predictor than self-efficacy, in that self-efficacy no longer predicted PA behaviour when included alongside enjoyment. In follow-up mediation analyses, enjoyment at six months did not mediate the effect of baseline self-efficacy on 12-month PA; however, six-month self-efficacy mediated the effect of baseline enjoyment on 12-month PA. CONCLUSION: Our results indicate that interventions should perhaps initially focus on increasing enjoyment of physical activity. Greater PA enjoyment appears to influence individuals' self-reported ability to engage in regular PA (i.e. higher self-efficacy ratings). Additional research is needed to better understand the interrelationships between self-efficacy and enjoyment and how these constructs affect PA. PMID- 26541891 TI - Is psychiatry in need of a course correction? PMID- 26541892 TI - Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia. AB - Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required. PMID- 26541893 TI - Reference periods in retrospective behavioral self-report: A qualitative investigation. AB - BACKGROUND: Self-report questions in substance use research and clinical screening often ask individuals to reflect on behaviors, symptoms, or events over a specified time period. However, there are different ways of phrasing conceptually similar time frames (eg, past year vs. past 12 months). METHODS: We conducted focused, abbreviated cognitive interviews with a sample of community health center patients (N = 50) to learn how they perceived and interpreted questions with alternative phrasing of similar time frames (past year vs. past 12 months; past month vs. past 30 days; past week vs. past 7 days). RESULTS: Most participants perceived the alternative time frames as identical. However, 28% suggested that the "past year" and "past 12 months" phrasings would elicit different responses by evoking distinct time periods and/or calling for different levels of recall precision. Different start and end dates for "past year" and "past 12 months" were reported by 20% of the sample. There were fewer discrepancies for shorter time frames. CONCLUSIONS: Use of "past 12 months" rather than "past year" as a time frame in self-report questions could yield more precise responses for a substantial minority of adult respondents. SCIENTIFIC SIGNIFICANCE: Subtle differences in wording of conceptually similar time frames can affect the interpretation of self-report questions and the precision of responses. PMID- 26541886 TI - Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. AB - The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age. PMID- 26541894 TI - TGF-beta induces the differentiation of human CXCL13-producing CD4(+) T cells. AB - In the ectopic lymphoid-like structures present in chronic inflammatory conditions such as rheumatoid arthritis, a subset of human effector memory CD4(+) T cells that lacks features of follicular helper T (Tfh) cells produces CXCL13. Here, we report that TGF-beta induces the differentiation of human CXCL13 producing CD4(+) T cells from naive CD4(+) T cells. The TGF-beta-induced CXCL13 producing CD4(+) T cells do not express CXCR5, B-cell lymphoma 6 (BCL6), and other Tfh-cell markers. Furthermore, expression levels of CD25 (IL-2Ralpha) in CXCL13-producing CD4(+) T cells are significantly lower than those in FoxP3(+) in vitro induced Treg cells. Consistent with this, neutralization of IL-2 and knockdown of STAT5 clearly upregulate CXCL13 production by CD4(+) T cells, while downregulating the expression of FoxP3. Furthermore, overexpression of FoxP3 in naive CD4(+) T cells downregulates CXCL13 production, and knockdown of FoxP3 fails to inhibit the differentiation of CXCL13-producing CD4(+) T cells. As reported in rheumatoid arthritis, proinflammatory cytokines enhance secondary CXCL13 production from reactivated CXCL13-producing CD4(+) T cells. Our findings demonstrate that CXCL13-producing CD4(+) T cells lacking Tfh-cell features differentiate via TGF-beta signaling but not via FoxP3, and exert their function in IL-2-limited but TGF-beta-rich and proinflammatory cytokine-rich inflammatory conditions. PMID- 26541896 TI - Reactions to the meta-analyses of the Prototype Willingness Model. PMID- 26541895 TI - Targeted exome sequencing profiles genetic alterations in leiomyosarcoma. AB - Leiomyosarcoma (LMS) belongs to the class of genetically complex sarcomas and shows numerous, often non-recurrent chromosomal imbalances and aberrations. We investigated a group of LMS using NGS platform to identify recurrent genetic abnormalities and possible therapeutic targets. Targeted exome sequencing of 230 cancer-associated genes was performed on 35 primary soft tissue and visceral (extra-uterine) LMS. Sequence data were analyzed to identify single nucleotide variants, small insertions/deletions (indels), and copy number alterations. Key alterations were further investigated using FISH assay. The study group included patients with median age of 64 years and median tumor size of 7 cm. The primary sites included retroperitoneal/intra-abdominal, extremity, truncal, and visceral. Thirty-one tumors were high grade LMS, while four were low grade. Losses of chromosomal regions involving key tumor suppressor genes PTEN (10q), RB1 (13q), CDH1 (16q), and TP53 (17p) were the most frequent genetic events. Gains mainly involved chromosome regions 17p11.2 (MYOCD) and 15q25-26 (IGF1R). The most frequent mutations were identified in the TP53 gene in 13 of 35 (37%) cases. FISH analysis showed amplification of the myocardin (MYOCD) gene in 5 of 25 (20%) cases analyzed. None of the four low grade LMS showed losses or mutations of PTEN or TP53 genes. Genetic complexity is the hallmark of LMS with losses of important tumor suppressor genes being a common feature. MYOCD, a key gene associated with smooth muscle differentiation, is amplified in a subset of both retroperitoneal and extremity LMS. Further studies are necessary to investigate the significance of gains/amplifications in the development of these tumors. PMID- 26541897 TI - Complete bone regeneration in hemophilic pseudotumor of the mandible. AB - Hemophilic pseudotumor (HP) is rare, seen in 1-2% of patients with hemophilia, and is extremely uncommon in the mandible. A 6-year-old boy with moderate hemophilia A presented to our hospital with left mandibular swelling. Based on clinical and radiological findings, a tentative diagnosis of HP was made. After factor VIII administration, the lesion was curetted and HP was confirmed on histopathology. The patient was treated with twice-weekly factor VIII until the lesion had completely resolved and bone had regenerated at 1 year. The best treatment for HP is not established; however, appropriate initial treatment and postoperative prophylaxis are effective. PMID- 26541898 TI - Haemoglobin kenitra identified in a Portuguese man with type 2 diabetes and pheochromocytoma. PMID- 26541900 TI - Proteomics of endometrial cancer diagnosis, treatment, and prognosis. AB - This review discusses the current status of proteomics technology in endometrial cancer diagnosis, treatment and prognosis. The first part of this review focuses on recently identified biomarkers for endometrial cancer, their importance in clinical use as well as the proteomic methods used in their discovery. The second part highlights some of the emerging mass spectrometry based proteomic technologies that promise to contribute to a better understanding of endometrial cancer by comparing the abundance of hundreds or thousands of proteins simultaneously. PMID- 26541899 TI - Enhanced response inhibition in experienced fencers. AB - The inhibition of a prepotent response is an essential executive function which enables us to suppress inappropriate actions in a given context. Individuals with fencing expertise exhibit behavioral advantages on tasks with high demands on response inhibition. This study examines the electrophysiological basis for the superior response inhibition in experienced fencers. In the Go/Nogo task where frequent stimuli required a motor response while reaction had to be withheld to rare stimuli, the fencers, compared with the non-fencers, exhibited behavioral as well as electrophysiological advantages when suppressing prepotent responses. The superior response inhibition in the fencers was characterized by enhanced Nogo-N2 and reduced Nogo-P3. Single-trial analysis revealed that the amplitude difference of the Nogo-N2 between two groups was caused by lower single-trial latency variability in the fencers (may be due to low attentional fluctuation and/or stable neural processing speed) while the amplitude difference of the Nogo-P3 resulted from truly weaker neural activity in the fencers (may be because few cognitive sources are needed and few control efforts are made). The two inhibition-related components are distinct neurophysiological indexes that, on the one hand, provide effective guidance to titrate the level of executive function in fencers, and on the other hand, facilitate to monitor fencers' improvement in the training process. PMID- 26541901 TI - Recombinant Helicoverpa armigera nucleopolyhedrovirus with arthropod-specific neurotoxin gene RjAa17f from Rhopalurus junceus enhances the virulence against the host larvae. AB - A recombinant Helicoverpa armigera nucleopolyhedrovirus (HearNPV) expressing the insect-selective neurotoxin (RjAa17f) from Cuban scorpion Rhopalurus junceus was constructed by replacing the UDP-glucosyltransferase gene (egt) using lambda-red homologous recombination system. Another egt deleted control HearNPV was constructed in a similar way by inserting egfp gene into the egt locus. One-step viral growth curve and viral DNA replication curve analysis confirmed that the recombination did not affect the viral growth and DNA replication in host cells. There is no discernable difference in occlusion-body morphogenesis between RjAa17f-HearNPV, Egfp-HearNPV and HZ8-HearNPV, which was confirmed by transmission electron microscopy analysis. However, the insecticidal activity of RjAa17f-HearNPV is enhanced against the third instar H. armigera larvae according to the bioassay on virulence comparison. There is a dramatic reduction (56.9%) in median lethal dose (LD50 ) and also a reduction (13.4%) in median survival time (ST50 ) for the recombinant RjAa17f-HearNPV compared to the HZ8-HearNPV, but only a 27.5% reduction in LD50 and 10.1% reduction in ST50 value when Egfp-HearNPV is compared with HZ8-HearNPV. The daily diet consumption analysis showed that the RjAa17f-HearNPV was able to inhibit the infected larvae feeding compared with the egt minus HearNPV. These results demonstrated that this novel recombinant RjAa17f HearNPV could improve the insecticidal effect against its host insects and RjAa17f could be a considerable candidate for other recombinant baculovirus constructions. PMID- 26541902 TI - Proliferative events and apoptotic remodelling in retinal development of common toad (Bufo bufo). AB - Proliferation and apoptosis are fundamental processes in the development of the retina, and a proper balance of the two phenomena is crucial to correct development of the organ. Despite intense investigation in different vertebrates, only a few studies have analyzed the cell death and the cell division quantitatively in the same species during development. Here we studied the time course of apoptosis and proliferation in the retina of common toad, Bufo bufo, and discuss the findings in an evolutionary perspective. We found cells that were dividing first scattered throughout the retina, then, in later stages, proliferation was confined to the ciliary marginal zone. This pattern was confirmed by the expression of the proliferative marker PCNA. Both proliferation and apoptosis occurred in successive waves, and two apoptotic peaks were detected: one at premetamorphosis 1 and the second at prometamorphosis. PARP-1, a known molecular marker of apoptosis, was used to confirm the data obtained by counting pyknotic nuclei. In summary, proliferative and apoptotic waves display an inverse time-relationship through development, with apoptotic peaks coinciding with low proliferation phases. In a comparative perspective, amphibians follow a developmental pattern similar to other vertebrates, although with different timing. PMID- 26541903 TI - Using probe-microphone measurements to improve the match to target gain and frequency response slope, as a function of earmould style, frequency, and input level. AB - OBJECTIVE: Matching a prescription gain target at 60-65 dB SPL does not ensure audibility of lower input levels, nor does it mean the fitted frequency response slope is conducive to good sound quality. The aim of the present study was to evaluate the use of probe-microphone measurements to match target gain and slope, as a function of earmould style, frequency, and input level. DESIGN: The real-ear insertion gain was calculated for an input of 50, 65, and 80 dB SPL for the manufacturer's 'initial fit' (IF) settings and after adjustment to target in 49 and 51 open slim-tube and custom earmould fittings, respectively. STUDY SAMPLE: One hundred adults with median age 74 years (range 32-93). RESULTS: Some 18%-67% of the IF settings were within 10 dB of the target gain but this increased to >85% after adjustment. Some 47%-71% of the IF settings were within 10 dB of the target slope but, with the exception of 2-4 kHz, this increased to >88% after adjustment. CONCLUSIONS: The results indicate that IF settings are inadequate, at least for the model of hearing aid used in the present study; however, significant discrepancies remained, even after adjustment. PMID- 26541904 TI - Low-dose metronomic chemotherapy with cisplatin enhanced immunity in a murine model of ectopic cervical cancer. AB - Previous researchers have claimed that metronomic low-dose/dense chemotherapy can enhance the therapeutic effectiveness of cisplatin treatment in the control of cancer. Therefore, the aim of this study was to explore the effectiveness of metronomic drug delivery with regards to its effects on adaptive immunity in a murine model of ectopic cervical cancer. The effectiveness of long-term low dose/dense cisplatin treatment in HPV E7-expressing TC-1 cells was evaluated via morphological observations. Tumour mass and survival curves were used to determine the antitumour effect against E7-expressing tumours. After experimental mice had been treated with low-dose/dense cisplatin therapy, flow cytometry was used to measure the expression of MHC class I surface antigens on cultured TC-1 cells. Splenocytes expressing both interferon (IFN)-gamma and CD8 responsible for E7 antigens and the Treg population were also quantified using flow cytometry. The results indicate that in vivo treatment with metronomic cisplatin suppresses the growth of cultured TC-1 cells. An increase was also observed in the number of splenocytes expressing both IFN-gamma and CD8 responsible for E7 antigens and the Treg population. These results support previous reports that metronomic low dose/dense cisplatin chemotherapy is an effective treatment against ectopic cervical cancer with E7-expression. PMID- 26541905 TI - Factors Associated With Infarct-Related Artery Patency Before Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction (from the FAST-MI 2010 Registry). AB - Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Using the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST MI) 2010 registry, we investigated factors related to IRA patency (thrombolysis in myocardial infarction [TIMI] 2/3 flow) at the start of procedure in patients admitted for primary percutaneous coronary intervention. FAST-MI 2010 is a nationwide French registry including 4,169 patients with acute MI. Of 1,452 patients with STEMI with primary percutaneous coronary intervention, 466 (32%) had TIMI 2/3 flow of IRA before the procedure. Mean age (62 +/- 14 years in both groups), Global Registry of Acute Coronary Event score (141 +/- 31 vs 142 +/- 34), and time from onset to angiography (472 +/- 499 vs 451 +/- 479 minutes) did not differ according to IRA patency (TIMI 2/3 vs TIMI 0/1). Using multivariate logistic regression analysis, IRA patency was more frequently found in patients having called earlier (time from onset to electrocardiogram [ECG] <120 minutes; odds ratio [OR] 1.49; 95% confidence interval [CI] 1.17 to 1.89), or receiving rapid-onset of action (prasugrel or glycoprotein IIb-IIIa) antiplatelet therapy in the prehospital setting (OR 1.59, 95% CI 1.14 to 2.21). Increasing time from diagnostic ECG to angiography was also associated with IRA patency (>90 minutes; OR 1.37, 95% CI 1.08 to 1.75). In conclusion, preprocedural IRA patency is observed in one third of patients with STEMI, it is more frequently found in patients having received fast-acting antiplatelet therapy before angiography, and in patients having called early. Higher IRA patency with increasing time delays from qualifying ECG to angiography suggests an additional role of spontaneous or medication-mediated fibrinolysis. PMID- 26541906 TI - Effects of Swimming and Cycling Exercise Intervention on Vascular Function in Patients With Osteoarthritis. AB - Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease. PMID- 26541907 TI - Insurance and Prehospital Delay in Patients <=55 Years With Acute Myocardial Infarction. AB - This prospective study assessed whether gender differences in health insurance help explain gender differences in delay in seeking care for patients in the US, with acute myocardial infarction (AMI). We also assessed gender differences in such prehospital delay for AMI in Spain, a country with universal insurance. We used data from 2,951 US and 496 Spanish patients aged 18 to 55 years with AMI. US patients were grouped by insurance status: adequately insured, underinsured, or uninsured. For each country, we assessed the association between gender and prehospital delay (symptom onset to hospital arrival). For the US cohort, we modeled the relation between insurance groups and delay of >12 hours. US women were less likely than men to be uninsured but more likely to be underinsured, and a larger proportion of women than men experienced delays of >12 hours (38% vs 29%). We found no association between insurance status and delays of >12 hours in men or women. Only 17.3% of Spanish patients had delays of >12 hours, and there were no significant gender differences. In conclusion, women were more likely than men to delay, although it was not explained by differences in insurance status. The lack of gender differences in prehospital delays in Spain suggests that these differences may vary by health care system and culture. PMID- 26541908 TI - Trends in Coronary Angiography, Revascularization, and Outcomes of Cardiogenic Shock Complicating Non-ST-Elevation Myocardial Infarction. AB - Early revascularization is the mainstay of treatment for cardiogenic shock (CS) complicating acute myocardial infarction. However, data on the contemporary trends in management and outcomes of CS complicating non-ST-elevation myocardial infarction (NSTEMI) are limited. We used the 2006 to 2012 Nationwide Inpatient Sample databases to identify patients aged >= 18 years with NSTEMI with or without CS. Temporal trends and differences in coronary angiography, revascularization, and outcomes were analyzed. Of 2,191,772 patients with NSTEMI, 53,800 (2.5%) had a diagnosis of CS. From 2006 to 2012, coronary angiography rates increased from 53.6% to 60.4% in patients with NSTEMI with CS (ptrend <0.001). Among patients who underwent coronary angiography, revascularization rates were significantly higher in patients with CS versus without CS (72.5% vs 62.6%, p <0.001). Patients with NSTEMI with CS had significantly higher risk adjusted in-hospital mortality (odds ratio 10.09, 95% confidence interval 9.88 to 10.32) as compared to those without CS. In patients with CS, an invasive strategy was associated with lower risk-adjusted in-hospital mortality (odds ratio 0.43, 95% confidence interval 0.42 to 0.45). Risk-adjusted in-hospital mortality, length of stay, and total hospital costs decreased over the study period in patients with and without CS (ptrend <0.001). In conclusion, we observed an increasing trend in coronary angiography and decreasing trend in in-hospital mortality, length of stay, and total hospital costs in patients with NSTEMI with and without CS. Despite these positive trends, overall coronary angiography and revascularization rates remain less than optimal and in-hospital mortality unacceptably high in patients with NSTEMI and CS. PMID- 26541909 TI - Indications and immediate and long-term results of a novel pericardium covered stent graft: Consecutive 5 year single center experience. AB - BACKGROUND: The use of covered stent grafts during percutaneous coronary intervention (PCI) is a life saving solution to seal acute iatrogenic vessel rupture. However, the presence of an impenetrable mechanical barrier is also appealing during treatment of friable coronary plaques but the synthetic PTFE membrane that might trigger excessive neointimal proliferation has limited its elective-use. Pericardium tissue may offer an appealing "natural" alternative. Aim of our study is to report the consecutive 5-year single center experience with the use of pericardium-covered stents (PCS) (ITGI-Medical, Israel) in a variety of emergency and elective applications. METHODS: Nineteen consecutive patients undergoing implantation of PCS at the Royal Brompton in the last 5 years. Reasons for PCS implantation included treatment of degenerated vein grafts, large coronary aneurysms, and acute iatrogenic vessel rupture. RESULTS: Angiographic success, defined as the ability of the device to be deployed in the indexed lesion with no contrast extravasation with residual angiographic stenosis <30% and a final thrombolysis in myocardial infarction (TIMI)-3 flow was achieved in all cases. Procedural success, defined as the achievement of angiographic success without any major adverse cardiovascular event (MACE) was achieved in 94.7% of patients. In-stent restenosis (ISR) was observed in 26.3% and all patients underwent successful target vessel revascularization with DES (mean time to restenosis 9.0 +/- 4.0 months). At a mean follow-up of 32.5 +/- 23.3 months no acute or late stent thrombosis was observed. CONCLUSION: PCSs were effective in the treatment of friable embolization-prone coronary plaques, sealing of acute iatrogenic vessel rupture and exclusion of large aneurysms with no thrombosis but high target lesion revascularization. PMID- 26541910 TI - Daylight-mediated photodynamic therapy for actinic damage in Latin America: consensus recommendations. AB - Although conventional photodynamic therapy (c-PDT) using methyl aminolevulinate cream (MAL) is effective for the treatment of grade I-II facial and scalp actinic keratosis (AK), it is associated with treatment-related pain for some patients. Daylight-mediated PDT (DL-PDT) has shown similar efficacy to c-PDT, was nearly painless, and was well tolerated. Overall, DL-PDT effectively treats AK and offers a simpler and better tolerated treatment option than c-PDT. This consensus panel provided recommendations on the use of DL-PDT in Latin America (LATAM) for the treatment of actinic damage associated with few or multiple AKs. The panel was comprised of eight dermatologists from different LATAM countries who have experience using PDT for the treatment of actinic damage. The panel reviewed the relevant literature and provided personal expertise with regard to using DL-PDT for the treatment of photodamage with or without AK. The recommendations formulated by the expert panel provide evidence-based guidelines on all aspects of DL-PDT for the treatment of actinic damage associated with AK in different regions of LATAM. These recommendations provide guidance for dermatologists to ensure maintenance of efficacy and safety of DL-PDT when treating actinic damage, associated with few or multiple AKs in sun-exposed skin. PMID- 26541911 TI - CYP2A6 Effects on Subjective Reactions to Initial Smoking Attempt. AB - INTRODUCTION: In very novice smokers, CYP2A6 genotypes that reduce nicotine metabolism to an intermediate rate may increase smoking risk, relative to both normal and slow rates. The present study examined the hypothesis that intermediate metabolism variants are associated with greater pleasurable effects of the initial smoking attempt than either normal or slow metabolism variants. METHODS: Participants were novice smokers (N = 261, 65% female) of European descent. Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 Diplotype Predicted Rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Subjective reactions to the initial smoking attempt were assessed by the Pleasurable Smoking Experiences (PSE) scale, which was collected within 3 years of the initial smoking attempt. The effect of CDPR on PSE was tested using a generalized linear model in which CDPR was dummy coded and Intermediate CDPR was the reference condition. Gender was included in the model as a control for higher PSE scores by males. RESULTS: Lower PSE scores were associated with Normal CDPR, beta = -0.34, P = .008, and Slow CDPR, beta = 0.52, P = .001, relative to Intermediate CDPR. CONCLUSIONS: Intermediate CDPR enhanced pleasurable effects of the initial smoking attempt relative to other CYP2A6 variants. This finding is consistent with the hypothesis that the risk effect of Intermediate CDPR on early smoking is a function of optimal pleasurable effects. IMPLICATIONS: This study supports our recent hypothesis that CYP2A6 diplotypes that encode intermediate nicotine metabolism rate are associated with enhanced pleasurable events following the initial smoking attempt, compared with diplotypes that encode either normal or slow metabolism. This hypothesis was offered to account for our unexpected previous finding of enhanced smoking risk in very novice smokers associated with intermediate metabolism rate. Our new finding encourages further investigation of time-dependent relations between CYP2A6 effects and smoking motives, and it encourages laboratory study of the mechanisms underlying the initial smoking enhancement in novice smokers associated with intermediate metabolism. PMID- 26541912 TI - Oestradiol Regulates Neuropeptide Y Release and Gene Coupling with the GABAergic and Glutamatergic Synapses in the Adult Female Rat Dentate Gyrus. AB - Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity affecting both GABAergic and glutamatergic transmission. Previously, we found that oestradiol modifies the number of NPY immunoreactive neurones in the hippocampal dentate gyrus. In the present study, we investigated which oestrogen receptor type is responsible for these changes in the number of NPY-positive neurones. Furthermore, we determined the effects of oestrogen receptor activation on NPY release. Finally, we examined the contribution of oestrogen toward the remodelling of the GABAergic and glutamatergic gene networks in terms of coupling with Npy gene expression in ovariectomised rats. We found that activation of either oestrogen receptor type (ERalpha or ERbeta) increases the number of NPY immunopositive neurones and enhances NPY release in the dentate gyrus. We also found that, compared to oestrogen-lacking ovariectomised rats, oestrogen replacement increases the probability of synergistic/antagonistic coupling between the Npy and GABAergic synapse genes, whereas the glutamatergic synapse genes are less likely to be coupled with Npy under similar conditions. The data together suggest that oestrogens play a critical role in the regulation of NPY system activity and are also involved in the coupling/uncoupling of the Npy gene with the GABAergic and glutamatergic synapses in the female rat dentate gyrus. PMID- 26541913 TI - Professional values of Turkish nurses: A descriptive study. AB - BACKGROUND: Professional values improve the quality of nurses' professional lives, reduce emotional exhaustion and depersonalization, increase personal success, and help to make collaborations with the members of the healthcare team more frequent. OBJECTIVE: The purpose of this study was to describe the professional values of Turkish nurses and to explore the relationships between nurses' characteristics. METHODS: This was a descriptive study of a convenience sample consisting of 269 clinical nurses. A questionnaire was used to identify socio-demographic characteristics, and the Nurses' Professional Values Scale was applied. Ethical considerations: Permission to conduct the study was received from the hospital and the Institutional Review Boards of the Suleyman Demirel University ethic committee. RESULTS: The mean scale score of the participant nurses was 165.41 +/- 20.79. The results of this study revealed that human dignity was the most important professional value for nurses, and the importance attached to these values showed statistically significant differences by age, length of service, educational level, marital status, position at work, and receiving relevant in-service training. CONCLUSION: Nurses' Professional Values Scale scores showed that nurses give above average and attached importance to professional values. PMID- 26541914 TI - Evaluation of affinity interaction between small molecules and platelets by open tubular affinity capillary electrochromatography. AB - In this paper, an open tubular affinity capillary electrochromatography (OT-ACEC) was developed by physical adsorption of rabbit platelets on the inner surface of capillary. The interactions between small molecules include adenosine diphosphate (ADP) (positive control), protocatechuic acid (negative control) and seven natural products (salvianolic acid B, salvianic acid A sodium, hydroxysafflor yellow A, ferulic acid, chlorogenic acid, sinapic acid, caffeic acid) and platelets were evaluated by their retention factors and binding constants obtained based on peak-shift assay. Then, the activities of anti-platelet aggregation induced by thrombin (THR), ADP and arachidonic acid (AA) for those small molecules (except ADP) were evaluated by turbidimetric method. The results indicate that: (i) ADP, a platelet aggregation inducer, had strong interaction with platelet, while protocatechuic acid that had no inhibition on platelet aggregation behaved no specific interaction; (ii) there was a positive correlation between the anti-platelet aggregation activities of small molecules and their interactions with platelet, generally those compounds with higher binding constants with platelet exhibited higher activities. Therefore, the OT ACEC method developed in the present study can be a potential method to evaluate affinity interactions between small molecules and platelets, so as to predict the biological activities such as anti-platelet aggregation for the small molecules. PMID- 26541916 TI - LCZ696 (sacubitril/valsartan): can we predict who will benefit? PMID- 26541915 TI - Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF. AB - BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255). PMID- 26541917 TI - Predictors and impact of myocardial injury after transcatheter aortic valve replacement: a multicenter registry. AB - BACKGROUND: Cardiac biomarker release signifying myocardial injury post transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown. OBJECTIVES: This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR. METHODS: This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up. RESULTS: Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (p < 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (p < 0.001). CONCLUSIONS: Some degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK MB levels associated with greater acute and late mortality, imparting a negative impact on left ventricular function. PMID- 26541918 TI - Clinical relevance of myocardial injury after transcatheter aortic valve replacement. PMID- 26541920 TI - Angina in revascularization of ischemic cardiomyopathy: the whole quilt, or just a STICH? PMID- 26541919 TI - Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH. AB - BACKGROUND: Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina. OBJECTIVES: This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD. METHODS: We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction <=35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long term clinical outcomes. RESULTS: At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01). CONCLUSIONS: Angina does not predict all cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). PMID- 26541922 TI - Going beyond the hard endpoints: "quality of life" may be dependent on quality of available data. PMID- 26541921 TI - Impact of multivessel revascularization on health status outcomes in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease. AB - BACKGROUND: Up to 65% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (MVCAD). Long-term health status of STEMI patients after multivessel revascularization is unknown. OBJECTIVES: This study investigated the relationship between multivessel revascularization and health status outcomes (symptoms and quality of life [QoL]) in STEMI patients with MVCAD. METHODS: Using a U.S. myocardial infarction registry and the Seattle Angina Questionnaire (SAQ), we determined the health status of patients with STEMI and MVCAD at the time of STEMI and 1 year later. We assessed the association of multivessel revascularization during index hospitalization with 1 year health status using multivariable linear regression analysis, and also examined demographic, clinical, and angiographic factors associated with multivessel revascularization. RESULTS: Among 664 STEMI patients with MVCAD, 251 (38%) underwent multivessel revascularization. Most revascularizations were staged during the index hospitalization (64.1%), and 8.0% were staged after discharge, with 27.9% performed during primary percutaneous coronary intervention. Multivessel revascularization was associated with age and more diseased vessels. At 1 year, multivessel revascularization was independently associated with improved symptoms (4.5 points higher SAQ angina frequency score; 95% confidence interval [CI]: 1.0 to 7.9) and QoL (6.6 points higher SAQ QoL score; 95% CI: 2.7 to 10.6). One-year mortality was not different between those who did and did not undergo multivessel revascularization (3.6% vs. 3.4%; log rank test p = 0.88). CONCLUSIONS: Multivessel revascularization improved angina and QoL in STEMI patients with MVCAD. Patient-centered outcomes should be considered in future trials of multivessel revascularization. PMID- 26541923 TI - Carotid stiffness is associated with incident stroke: a systematic review and individual participant data meta-analysis. AB - BACKGROUND: Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent. OBJECTIVES: This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV. METHODS: This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual level data of all cohort studies with available data on carotid stiffness and cfPWV. RESULTS: Ten studies (n = 22,472) were included in the aggregate data meta analysis and 4 (n = 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]). CONCLUSIONS: Carotid stiffness is associated with incident stroke independently of CV factors and aortic stiffness. In addition, carotid stiffness improves stroke risk prediction beyond Framingham and aortic stiffness. PMID- 26541924 TI - Carotid stiffness and cerebrovascular disease: the physiology beyond the anatomy. PMID- 26541925 TI - The role of the clinical pharmacist in the care of patients with cardiovascular disease. AB - Team-based cardiovascular care, including the use of clinical pharmacists, can efficiently deliver high-quality care. This Joint Council Perspectives paper from the Cardiovascular Team and Prevention Councils of the American College of Cardiology provides background information on the clinical pharmacist's role, training, certification, and potential utilization in a variety of practice models. Selected systematic reviews and meta-analyses, highlighting the benefit of clinical pharmacy services, are summarized. Clinical pharmacists have a substantial effect in a wide variety of roles in inpatient and ambulatory settings, largely through optimization of drug use, avoidance of adverse drug events, and transitional care activities focusing on medication reconciliation and patient education. Expansion of clinical pharmacy services is often impeded by policy, legislation, and compensation barriers. Multidisciplinary organizations, including the American College of Cardiology, should support efforts to overcome these barriers, allowing pharmacists to deliver high-quality patient care to the full extent of their education and training. PMID- 26541926 TI - Cardiac risk of noncardiac surgery. AB - Major perioperative cardiac events are estimated to complicate between 1.4% and 3.9% of surgeries. Because most surgeries are elective, there is the opportunity to implement strategies to reduce this risk. Accurate identification of patients at risk for such events will allow patients to be better informed about the benefit-to-risk ratio of procedures, and guide allotment of limited clinical resources, utilization of preventive interventions, and areas of future research. This review focuses on important features of the initial pre-operative clinical risk assessment, indications for diagnostic testing to quantify cardiac risk, and the methods and indications for pre-emptive therapies. PMID- 26541927 TI - A moment of reflection on the past and future of the Association of Black Cardiologists: the history, legacy, and relevance of a socially conscious organization dedicated to cardiovascular health equity. PMID- 26541928 TI - Characterization of the first PCSK9 gain of function homozygote. PMID- 26541929 TI - Prediction of long-term survival after liver transplantation for familial transthyretin amyloidosis. PMID- 26541930 TI - Neglecting enterococci may lead to a misinterpretation of the consequences of last changes in endocarditis prophylaxis American Heart Association guidelines. PMID- 26541931 TI - Vasa vasorum: still an invisible factor? PMID- 26541932 TI - Reply: neglecting enterococci may lead to a misinterpretation of the consequences of last changes in endocarditis prophylaxis American Heart Association guidelines. PMID- 26541933 TI - Reply: vasa vasorum: still an invisible factor? PMID- 26541934 TI - Copper Sulfide Nanocrystal Level Structure and Electrochemical Functionality towards Sensing Applications. AB - The level structure of copper sulfide nanocrystals of different sizes was investigated by correlating scanning tunneling spectroscopy and cyclic voltammetry data in relation to sensing applications. Upon oxidation of Cu2 S nanocrystals in the low-chalcocite phase, correlated changes are detected by both methods. The cyclic voltammetry oxidation peak of Cu(1+) down shifts, while in gap states, adjacent to the valence-band edge, appeared in the tunneling spectra. These changes are attributed to Cu vacancy formation leading to a Cu depleted phase of the nanocrystals. The relevance of the oxidation to the use of copper sulfide nanocrystals in hydrogen peroxide sensing was also addressed, showing that upon oxidation the sensitivity vanishes. These findings bare significance to the use of copper sulfide nanocrystals in glucose sensing applications. PMID- 26541935 TI - Patient-based outcomes following surgical debridement and flap coverage of digital mucous cysts. AB - PURPOSE: The purpose of this prospective cohort study was to evaluate patient based outcomes and complications following excision of mucous cysts, joint debridement, and closure with one of three types of local flaps. METHODS: From 2000-2011, 35 consecutive patients with 37 digital mucous cysts were treated surgically. The surgical procedure included excision of the cyst together with the attenuated skin, joint debridement on the affected side including capsulectomy, and removal of osteophytes. Depending on the size and location of the cyst, the skin defect was covered by a transposition flap (31 cysts), an advancement flap (two cysts), or a rotation flap (four cysts). RESULTS: At an average follow-up time of 4 years, 4 months, there was no wound infection, flap necrosis, or joint stiffness. Preoperative nail ridging resolved in seven of nine fingers, and no nail deformities developed after surgery. One cyst, treated with a transposition flap, recurred 10 months after surgery. The average satisfaction score for the affected finger significantly improved from 4.3 to 6.8, and the average pain score decreased from 4.7 to 2.3. CONCLUSION: This treatment protocol provides reliable results. Patients were satisfied with the reduction of associated pain and the postoperative appearance of the treated finger, and postoperative complications were minimal. PMID- 26541936 TI - Rethinking the connection between working memory and language impairment. AB - BACKGROUND: Working memory deficits have been found for children with specific language impairment (SLI) on tasks imposing increasing short-term memory load with or without additional, consistent (and simple) processing load. AIMS: To examine the processing function of working memory in children with low language (LL) by employing tasks imposing increasing processing loads with constant storage demands individually adjusted based on each participant's short-term memory capacity. METHODS & PROCEDURES: School-age groups with LL (n = 17) and typical language with either average (n = 28) or above-average nonverbal intelligence (n = 15) completed complex working memory-span tasks varying processing load while keeping storage demands constant, varying storage demands while keeping processing load constant, simple storage-span tasks, and measures of language and nonverbal intelligence. Teachers completed questionnaires about cognition and learning. OUTCOMES & RESULTS: Significantly lower scores were found for the LL than either matched group on storage-based tasks, but no group differences were found on the tasks varying processing load. Teachers' ratings of oral expression and mathematics abilities discriminated those who did or did not complete the most challenging cognitive tasks. CONCLUSIONS & IMPLICATIONS: The results implicate a deficit in the phonological storage but not in the central executive component of working memory for children with LL. Teacher ratings may reveal personality traits related to perseverance of effort in cognitive research. PMID- 26541938 TI - Modelling considerations in the analysis of associations between antimicrobial use and resistance in beef feedlot cattle. AB - A number of sophisticated modelling approaches are available to investigate potential associations between antimicrobial use (AMU) and resistance (AMR) in animal health settings. All have their advantages and disadvantages, making it unclear as to which model is most appropriate. We used advanced regression modelling to investigate AMU-AMR associations in faecal non-type-specific Escherichia coli (NTSEC) isolates recovered from 275 pens of feedlot cattle. Ten modelling strategies were employed to investigate AMU associations with resistance to chloramphenicol, ampicillin, sulfisoxazole, tetracycline and streptomycin. Goodness-of-fit statistics did not show a consistent advantage for any one model type. Three AMU-AMR associations were significant in all models. Recent parenteral tetracycline use increased the odds of finding tetracycline resistant NTSEC [odds ratios (OR) 1.1-3.2]; recent parenteral sulfonamide use increased the odds of finding sulfisoxazole-resistant NTSEC (OR 1.4-2.5); and recent parenteral macrolide use decreased the odds of recovering ampicillin resistant NTSEC (OR 0.03-0.2). Other results varied markedly depending on the modelling approach, emphasizing the importance of exploring and reporting multiple modelling methods based on a balanced consideration of important factors such as study design, mathematical appropriateness, research question and target audience. PMID- 26541937 TI - Adjuvant use of antibiotics with corticosteroids in inflammatory bowel disease exacerbations requiring hospitalisation: a retrospective cohort study and meta analysis. AB - BACKGROUND: Patients hospitalised with an exacerbation of inflammatory bowel disease (IBD) often receive antibiotics in addition to intravenous steroids. However, their efficacy in this setting is unclear. AIM: To ascertain if the addition of antibiotics to intravenous steroids modifies short and long-term clinical outcomes. METHODS: Our study included IBD patients hospitalised between 2009 and 2014 who received intravenous (IV) steroids with or without adjuvant antibiotics. Outcomes of interest included length of stay (LOS), need for medical and surgical rescue therapy during the hospitalisation, and at 90 and 365 days. A meta-analysis of previously published randomised trials was additionally performed. RESULTS: A total of 354 patients were included [145 ulcerative colitis (UC); 209 Crohn's disease (CD)]. In CD, combination of IV steroids and antibiotics did not change need for in-hospital medical rescue therapy, surgery or hospitalisations at 1 year but was associated with greater LOS (6.1 vs. 4.6 days, P = 0.02). In UC, patients receiving antibiotics were less likely to require in-hospital medical rescue therapy [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.93] but experienced no statistically significant differences in LOS, in-hospital surgery, re-hospitalisations or surgery by 1 year. A meta-analysis of three relevant randomised trials demonstrated no difference in clinical improvement with antibiotics over placebo (OR: 1.08, 95% CI: 0.50-2.32). CONCLUSIONS: The addition of antibiotics to intravenous steroids for treatment of IBD exacerbations was associated with a reduced need for in hospital medical rescue therapy in ulcerative colitis without significant long term benefit, and did not affect short- or long-term outcomes in Crohn's disease. PMID- 26541939 TI - De novo protein conformational sampling using a probabilistic graphical model. AB - Efficient exploration of protein conformational space remains challenging especially for large proteins when assembling discretized structural fragments extracted from a protein structure data database. We propose a fragment-free probabilistic graphical model, FUSION, for conformational sampling in continuous space and assess its accuracy using 'blind' protein targets with a length up to 250 residues from the CASP11 structure prediction exercise. The method reduces sampling bottlenecks, exhibits strong convergence, and demonstrates better performance than the popular fragment assembly method, ROSETTA, on relatively larger proteins with a length of more than 150 residues in our benchmark set. FUSION is freely available through a web server at http://protein.rnet.missouri.edu/FUSION/. PMID- 26541942 TI - FDA urged to reduce REMS program burdens. PMID- 26541941 TI - A relay strategy for the mercury (II) chemodosimeter with ultra-sensitivity as test strips. AB - A relay strategy has been proposed to design a new Hg(2+) chemodosimeter (TPE-S), by coupling Hg(2+)-promoted deprotection reaction with ketone-enol isomerization, realizing the multistage amplifying effect. Changes in both of color and fluorescence could occur immediately, and TPE-S displayed high selectivity for Hg(2+), other metal ions (Ag(+), Fe(3+), Cu(2+), Pb(2+), Co(2+), Cr(3+), Al(3+), Cd(2+), Mg(2+), Mn(2+), Ba(2+), Fe(2+), Ca(2+), Ni(2+), Zn(2+), Li(+), K(+) and Na(+)) gave nearly no disturbance to the sensing process. When fabricated as test strips similar to pH-indicator papers, immediate color change from colorless to purple could be visually observed by naked-eyes without the aid of any additional equipment, with the detection limit as low as 1 * 10(-7) M (Hg(2+) in aqueous solution). Due to its easy synthesis, high selectivity and sensitivity, combined with the portable test strips, TPE-S could be developed as a convenient and cost effective tool for the detection of Hg(2+) in on-site inspections. PMID- 26541943 TI - Pharmacists find ways to make ADCs work in the ED. PMID- 26541940 TI - Late Na(+) current and protracted electrical recovery are critical determinants of the aging myopathy. AB - The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na(+) current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca(2+) cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca(2+) transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly. PMID- 26541944 TI - FIP hospital pharmacy section releases new version of Basel Statements. PMID- 26541945 TI - Interdisciplinary care team advocate Thomas J. Mattei dies at 70. PMID- 26541946 TI - Substitution of sodium acetate for sodium bicarbonate for urine alkalinization in high-dose methotrexate therapy. PMID- 26541947 TI - Development of a discharge pharmacy service. PMID- 26541948 TI - Tips for succeeding at pharmacy residency phone interviews. PMID- 26541949 TI - Empagliflozin: a sodium-glucose cotransporter 2 inhibitor for treatment of type 2 diabetes. AB - PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, dosage and administration, and drug-drug interactions of empagliflozin are reviewed. SUMMARY: Empagliflozin is a direct inhibitor of sodium-glucose cotransporter 2 (SGLT2), which acts to lower the renal threshold and increase urinary glucose excretion. SGLT2 is found in the proximal tubules of the kidneys and reabsorbs about 90% of the filtered glucose. Because the mechanism of action of empagliflozin is not insulin dependent or insulin sensitive, it may be used in patients at different stages of diabetes with nonfunctional or impaired pancreatic beta cells. Furthermore, empagliflozin can be used with other antidiabetic drugs due to its lack of any additive hypoglycemic effects. Long-term efficacy studies revealed significant reductions with empagliflozin in glycosylated hemoglobin (HbA1c) values at week 78 compared with placebo. Secondary endpoints in clinical trials showed improvements in lowering blood pressure and reductions in body weight. The risk:benefit ratio must be assessed for empagliflozin as the safety profile includes an increase in urinary and genital infections. CONCLUSION: Empagliflozin has shown efficacy in lowering HbA1c and blood glucose levels both as monotherapy and as an add-on to existing therapy. Despite the drug's promising outlook, empagliflozin also leads to common but serious adverse events not seen with other classes of antihyperglycemic agents. Considering the current data on its efficacy and its safety profile, empagliflozin can be used as a second- or third-line agent in treating diabetes. PMID- 26541950 TI - Acetylcysteine for treatment of autism spectrum disorder symptoms. AB - PURPOSE: Successful use of acetylcysteine to control irritability and aggressive behaviors in a hospitalized adolescent patient with autism spectrum disorder (ASD) is described. SUMMARY: A 17-year-old Hispanic male with ASD and intellectual disability was hospitalized for inpatient psychiatric treatment due to impulsive and violent behavior. Despite receiving various medications in the initial weeks of hospitalization, including intramuscular lorazepam and diphenhydramine injections (four days a week on average), the patient continued to exhibit aggressive and unpredictable behaviors. Treatment with 20% acetylcysteine oral solution was initiated at a dosage of 600 mg twice daily as an adjunct to quetiapine therapy. Over the next six weeks, reductions in the patient's aggressive behavior, tantrums, and irritability were noted. The use of as-needed medications to control aggression was decreased, and the dosage of quetiapine was lowered from 700 to 400 mg daily over the course of the hospitalization. Acetylcysteine was well tolerated, with no observed or reported adverse effects. Unlike clonidine or guanfacine (other medications used for ASD related behavioral symptoms), acetylcysteine is not sedating; moreover, it lacks the metabolic, extrapyramidal, and endocrine adverse effects of atypical antipsychotics. Published data from small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; these therapeutic benefits may be associated with acetylcysteine's glutamatergic, dopaminergic, antioxidant, and anti-inflammatory properties. CONCLUSION: Treatment with acetylcysteine improved ASD symptoms, including irritability and aggression, in a teenage patient. PMID- 26541951 TI - Effect of i.v. acetaminophen on total hip or knee replacement surgery: a case matched evaluation of a national patient database. AB - PURPOSE: The effects of i.v. acetaminophen on adverse events, hospital length of stay (LOS), and overall hospital costs for total hip or knee replacements were evaluated. METHODS: We conducted a matched-pairs analysis of adult inpatients who underwent elective total hip arthroplasty or total knee arthroplasty in hospitals participating in the Premier Healthcare Alliance from January 1, 2011, to November 30, 2012. Each case who received i.v. acetaminophen on the day of surgery was matched to a control who did not receive i.v. acetaminophen within the same hospital. Treatment groups were analyzed for differences in the rate of adverse effects, LOS, and hospital resource utilization. RESULTS: A total of 22,146 cases and controls were similar in terms of age, race, sex, marital status, insurance status, and preoperative comorbidities. Overall adverse events were significantly lower with i.v. acetaminophen (24.3%) than with controls (26.3%, p < 0.001), numerically less frequent in all subgroups, and significantly less frequent for renal, infectious, and miscellaneous adverse events (all p < 0.05). I.V. acetaminophen was also associated with a shorter LOS, with 1 out of 11 patients discharged one day earlier (p < 0.001) and lower average hospital costs: $16,381 for cases compared with $16,927 for controls (p < 0.001). Cost savings estimated by structural equation modeling of $547 per patient were due to $325 from direct effects and $222 from indirect effects, the latter mediated through adverse events and reduced LOS. CONCLUSION: In this retrospective cohort study of case-matched patients who underwent total hip or knee replacement surgery, multimodal analgesia with i.v. acetaminophen was associated with improved clinical outcomes in terms of fewer adverse events, shortened LOS, and reduced total hospital resources compared with patients who did not receive i.v. acetaminophen. PMID- 26541952 TI - Using institutional track programs and block scheduling to help students prepare for postgraduate residency training. AB - PURPOSE: The development and implementation of institutional track programs and block scheduling to help students prepare for postgraduate residency training are described. SUMMARY: Institutional track and block scheduling models were implemented into advanced pharmacy practice experience rotations to provide students with several of these experiences at the same practice site. Students at Purdue University College of Pharmacy (PUCOP) and Butler University College of Pharmacy and Health Sciences (BUCOPHS) can apply for an institutional track or block schedule. The application process for the institutional track and block scheduling programs provides students with an opportunity to refine written and oral skills that are necessary for residency applications and interviews, since the process mimics that of the ASHP Resident Matching Program. Students are frequently provided with mentors to assist in the residency or fellowship preparation, curriculum vitae or cover letter design, and career planning. Students at the site may also be paired with pharmacy residents enrolled in blocked rotations to serve as mentors. The top students are matched with a practice site and then assigned to five consecutive patient care rotations. Since 2011, a total of 71 students have participated in institutional tracks at PUCOP or block scheduling at BUCOPHS. Most institutional track students (83%) and block scheduling students (81%) were successful in matching to residency programs or hospital pharmacy positions after graduation. CONCLUSION: Block scheduling and institutional track programs were offered to students at two colleges of pharmacy interested in pursuing postgraduate residency training. Most institutional track students and block scheduling students successfully matched to residency programs or hospital pharmacy positions after graduation. PMID- 26541953 TI - Major publications in the critical care pharmacotherapy literature: January December 2014. AB - PURPOSE: Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials. PMID- 26541954 TI - Achieving blood pressure control among renal transplant recipients by integrating electronic health technology and clinical pharmacy services. AB - PURPOSE: The implementation and outcomes of a program combining electronic home blood pressure monitoring (HBPM) and pharmacist-provided medication therapy management (MTM) services in a renal transplantation clinic are described. SUMMARY: Patients enrolled in the program were provided with a computer-enabled blood pressure monitor. A dedicated renal transplantation pharmacist was integrated into the renal transplantation team under a collaborative care practice agreement. The collaborative care agreement allowed the pharmacist to authorize medication additions, deletions, and dosage changes. Comprehensive disease and blood pressure education was provided by a clinical pharmacist. In the pretransplantation setting, the pharmacist interviewed the renal transplant candidate and documents allergies, verified the patient's medication profile, and identified and assessed barriers to medication adherence. A total of 50 renal transplant recipients with at least one recorded home blood pressure reading and at least one year of follow-up were included in our analysis. A significant reduction in mean systolic and diastolic blood pressure values were observed at 30, 90, 180, and 360 days after enrollment in the program (p < 0.05). Pharmacist interventions were documented for 37 patients. Medication-related problems accounted for 46% of these interventions and included dosage modifications, regimen changes, and mitigation of barriers to medication access and adherence. CONCLUSION: Implementation of electronic HBPM and pharmacist-provided MTM services implemented in a renal transplant clinic was associated with sustained improvements in blood pressure control. Incorporation of a pharmacist in the renal transplant clinic resulted in the detection and resolution of medication related problems. PMID- 26541956 TI - Immunogenicity evaluation strategy for a second-generation therapeutic, PEG-IFN beta-1a. AB - AIMS: Neutralizing antibodies can diminish clinical efficacy of IFN-beta in multiple sclerosis patients. Therefore, monitoring immunogenicity was considered critical during clinical development of a second-generation, pegylated IFN-beta product, PEG-IFN-beta-1a. MATERIALS & METHODS: Assays previously used to evaluate immunogenicity of IFN-beta-1a were used to assess PEG-IFN-beta-1a immunogenicity, with modifications to apply current best bioanalytical practices. A separate testing paradigm was used to monitor antibodies to polyethylene glycol. RESULTS & CONCLUSION: Final assay cut points and relevant titer levels were established in study. Immunogenicity evaluation strategies for second-generation therapeutics should take into consideration current best bioanalytical practices while retaining consistency with legacy assays to facilitate data comparison and interpretation. This study illustrates challenges in assessing immunogenicity of second-generation therapeutics. PMID- 26541955 TI - In silico characterization and Molecular modeling of double-strand break repair protein MRE11 from Phoenix dactylifera v deglet nour. AB - BACKGROUND: DNA double-strand breaks (DSBs) are highly cytotoxic and mutagenic. MRE11 plays an essential role in repairing DNA by cleaving broken ends through its 3' to 5' exonuclease and single-stranded DNA endonuclease activities. METHODS: The present study aimed to in silico characterization and molecular modeling of MRE11 from Phoenix dactylifera L cv deglet nour (DnMRE11) by various bioinformatic approaches. To identify DnMRE11 cDNA, assembled contigs from our cDNA libraries were analysed using the Blast2GO2.8 program. RESULTS: The DnMRE11 protein length was 726 amino acids. The results of HUMMER show that DnMRE11 is formed by three domains: the N-terminal core domain containing the nuclease and capping domains, the C-terminal half containing the DNA binding and coiled coil region. The structure of DnMRE11 is predicted using the Swiss-Model server, which contains the nuclease and capping domains. The obtained model was verified with the structure validation programs such as ProSA and QMEAN servers for reliability. Ligand binding studies using COACH indicated the interaction of DnMRE11 protein with two Mn(2+) ions and dAMP. The ConSurf server predicted that residues of the active site and Nbs binding site have high conservation scores between plant species. CONCLUSIONS: A model structure of DnMRE11 was constructed and validated with various bioinformatics programs which suggested the predicted model to be satisfactory. Further validation studies were conducted by COACH analysis for active site ligand prediction, and revealed the presence of six ligands binding sites and two ligands (2 Mn(2+) and dAMP). PMID- 26541957 TI - Fast and sensitive HPLC method for the determination of neopterin, kynurenine and tryptophan in amniotic fluid, malignant effusions and wound exudates. AB - AIM: A new HPLC method for the determination of neopterin, kynurenine and tryptophan using a second-generation monolith stationary phase and high throughput sample preparation procedure based on microplates was developed and fully validated. MATERIALS & METHODS: As the stationary phase a monolithic C18 Chromolith high-resolution column with dimensions of 4.6 * 100 mm connected to a monolithic 4.6 * 10-mm security guard was used. Separation was achieved using 15 mM phosphate buffer (KH2PO4 +K2HPO4.3H2O at pH 3) and acetonitrile in gradient mode. RESULTS: Target analytes were determined in 5.5 minutes in amniotic fluid, effusions and wound exudates with a limit of quantification (LOQ) of 1.25 nM for neopterin, 2.5 uM for tryptophan and 0.25 uM for kynurenine. DISCUSSION: The method was applied to real clinical sample measurements, and it will be used to monitor neopterin, kynurenine and tryptophan levels in biological fluids to assess the patient response to therapy and clinical status. PMID- 26541958 TI - The Warden procedure can be successfully performed using minimally invasive cardiac surgery without aortic clamping. AB - Currently, minimally invasive cardiac surgery has found widespread use even in congenital heart surgery. The number of defects, which can be corrected through a small incision or totally endoscopic, is on the rise. Nowadays, surgeons can repair atrial septal defect, ventricular septal defect, patent ductus arteriosus and other congenital heart defects using minimally invasive techniques. In this paper, we report 21 cases of successful repair of supracardiac partial anomalous right upper and middle pulmonary venous connection, using the Warden procedure. It was performed in children through the right-sided midaxillary thoracotomy with direct cardiopulmonary bypass cannulation and induction of ventricular fibrillation. There were no operative or early postoperative deaths or complications. All patients were in sinus rhythm at discharge. According to echocardiography, there were no cases of early SVC or pulmonary veins narrowing. The Warden procedure can be performed safely and efficiently using the minimally invasive cardiac surgery. PMID- 26541959 TI - Iatrogenic aortic root and left main dissection during non-emergency coronary surgery: a solution applicable to heavily calcified coronary arteries?. AB - Dissection of the left main coronary artery during coronary artery bypass graft (CABG) surgery is a rare, potentially lethal complication, usually diagnosed at post-mortem. During the cross-clamp period of a 4-vessel coronary artery bypass graft procedure in a 74-year old hypertensive woman, retrograde dissection occurred in a diffusely diseased marginal artery when perfused with cardioplegic solution at a pressure of 140-150 mmHg through a vein graft. The dissection extended back to the left main artery, included the posterior proximal ascending aorta and then down the left anterior descending artery (LAD). Transoesophageal echocardiography (TOE) confirmed the left main dissection and showed anterior septal-lateral akinesis in a previously normally functioning left ventricle (LV). The circumferentially calcified proximal LAD was grafted with a saphenous vein by carving an oval area of calcium creating an elliptical opening in the artery wall. Normal LV function returned and, in the area of the left main dissection, there was only thickening with no colour flow. Eight months postoperatively cardiac catheterization showed normal LV function, patent vein grafts to the right coronary artery and proximal LAD, left internal mammary artery to distal LAD and an occluded sequential marginal vein graft. Twelve years postoperatively, the patient is well with Class I angina, on medication. There is no previous documentation of a diagnosed and successfully treated left main dissection during CABG surgery. Since this case using the technique of creating an oval opening in a circumferentially calcified coronary artery (with an otherwise satisfactory lumen), the author has been using this technique to bypass otherwise non bypassable arteries; this technique may be useful to help patients with severe calcific coronary artery disease. PMID- 26541960 TI - Intraoperative bronchial stump air leak control by Progel(r) application after pulmonary lobectomy. AB - Diffuse tracheobronchial calcification is a physiological condition associated with advanced age, especially in women. A calcified bronchus can be fractured during major lung resections (lobectomy, bilobectomy, and pneumonectomy), exposing patients to intraoperative air leakage and broncho-pleural fistula (BPF) occurrence. We retrospectively evaluated the use of Progel(r) application on the suture line of bronchial stump after pulmonary lobectomy analysing the intraoperative air leak and BPF occurrence. Between January 2014 and December 2014, Progel(r) was applied in 11 patients who presented intraoperative bronchial fractures after suture resection by mechanical staplers and air leak from bronchial stump, in order to treat air leakage. Patients were 7 men and 4 women, aged between 56 and 81 years (mean age 71.2 +/- 12.1 years). Surgical procedures included 6 upper lobectomies (4 right, 2 left), 1 bilobectomy and 4 lower lobectomies (3 right, 1 left). Mean hospital stay was 4.5 +/- 2.6 days (2-8 days). None of the patients had postoperative air leakage. No Progel(r) application-related complications occurred. No other major complications occurred. No mortality occurred. Progel(r) proved to be useful in treating intraoperative air leakage during major lung resections, particularly those occurring as a result of fracture of the bronchus from a mechanical stapler. PMID- 26541961 TI - The TEVAR App: a contemporary guide to thoracic endovascular aortic repair?. AB - There is a growing number of devices used for thoracic endovascular aortic repair (TEVAR). The designs of stent grafts and their delivery systems differ substantially. The success of TEVAR is based on the correct use of stent graft delivery systems, the identification and understanding of radiopaque markers, and the stent graft's accurate placement. In this brief communication, we introduce the TEVAR App-a novel guide for thoracic endovascular aortic repair. It is a tool that provides key information that is quick to access and easy to understand on the thoracic aortic stent grafts currently available. It includes instructions for use, animations demonstrating the stent grafts' deployment, troubleshooting information, size tables, the locations of radiopaque markers, stent graft and delivery system photos, chest X-rays, and information on magnetic resonance safety and compatibility. Furthermore, it contains the TEVAR Calculator, which assists one in planning stent graft size according to individual aortic dimensions and oversizing factors. The TEVAR App is cost-free, and its development has not been supported financially by any industry. It is a non profit project that aims to educate and help physicians performing TEVARs. PMID- 26541962 TI - Cardiac Amorphous Tumor on the Mitral Valve. PMID- 26541963 TI - Testing the effectiveness of a mentoring intervention to improve social participation of adolescents with visual impairments: study protocol for a randomized controlled trial. AB - BACKGROUND: Social participation is challenging for people with visual impairments. As a result, on average, social networks are smaller, romantic relationships formed later, educational achievements lower, and career prospects limited. Adolescents on their way towards achieving these goals may benefit from the knowledge and experience of adults who have overcome similar difficulties. Therefore, a mentoring intervention, called Mentor Support, will be set up and studied in which adolescents with visual impairments are matched with successfully social participating adults with and without visual impairments. The main objective of this study is to evaluate the effectiveness of Mentor Support. Secondary aims are to distinguish the importance of the disability-specific experience of mentors, predictors of success, and mediating factors. METHODS/DESIGN: The effect of Mentor Support will be tested in a randomized clinical trial, using pre-test one week before starting, post-test after 12 months, and follow-up after 18 months. Participants will be referred to one of the experimental groups or the control group, and this randomization will be stratified according to country region. Three groups are included in the trial: 40 participants will receive Mentor Support by mentors with a visual impairment in combination with care-as-usual, 40 participants will receive Mentor Support by mentors without visual impairments in combination with care-as-usual, and 40 participants will receive care-as-usual only. Mentor Support consists of 12 face to-face meetings of the mentee with a mentor with an overall time period of one year. On a weekly basis, dyads have contact via email, the Internet, or telephone. The primary outcome measure is improved social participation within three domains (work/school, leisure activities, and social relationships). Mediator variables are psychosocial functioning and self-determination. Predictors such as demographics and personality are also investigated in order to distinguish the pathways to successful social participation. Intention-to-treat and completer analyses will be conducted. DISCUSSION: The primary outcomes of this trial regard increased social participation. The study may yield insights to further improve effects of support programs to adolescents with visual impairments. TRIAL REGISTRATION: Netherlands Trial Register NTR4768 (registered 4 September 2014). PMID- 26541964 TI - The Impact of Geniculate Artery Collateral Circulation on Lower Limb Salvage Rates in Injured Patients. AB - BACKGROUND: This study aimed to determine the association between geniculate artery flow on admission computed tomography (CT) angiography and limb salvage outcomes in patients with lower extremity arterial injury. METHODS: All injured patients at a level I trauma center with CT angiogram (CTA) confirmed limited or no flow to the tibial vessels were included. Demographics, injury severity score (ISS), mechanism of injury, physiological parameters, the presence of geniculate artery collateral circulation (superior medial, superior lateral, medial, inferior medial, inferior lateral), and 30-day limb salvage outcome were recorded. Statistical analysis was completed using descriptive statistics and the chi-squared tests. RESULTS: From 2009 to 2012, a total of 84 patients with lower extremity arterial injury underwent diagnostic evaluation with CTA on admission that confirmed limited or no flow to the tibial vessels. A total of 10 patients (12%) underwent amputation. Primary amputation was performed in 3 (4%) patients, and secondary amputation was performed in 7 (8%) patients. There was no difference in age, gender, ISS, extremity abbreviated injury score, mechanism of injury, admission systolic blood pressure, heart rate, respiratory rate, transfusion volume, or type of vascular interventions between patients who had successful limb salvage and those who received an amputation. The number of patent geniculate arterial vessels was inversely associated with amputation with 3.3 patent geniculate arteries in the limb salvage group compared to 2.1 in the amputation group (P < 0.05). The 2 geniculate artery vessels that were significantly associated with limb salvage were the superior lateral geniculate and the inferior medial geniculate arteries (P < 0.05). CONCLUSIONS: Geniculate collateral circulation may have an important role in limb salvage after lower extremity vascular injury. The geniculate arteries that are associated with the highest rates of limb salvage appear to be the superior lateral geniculate and the inferior medical geniculate artery. PMID- 26541965 TI - Treatment of Abdominal Aortic Aneurysms in Cancer Patients. AB - BACKGROUND: The aim of this study was to analyze the outcomes of oncologic patients with associated aneurysm of the abdominal aorta (AAA), treated at a specialized cancer (Ca) hospital more than a 10-year period. METHODS: This was a retrospective study, and the data were obtained from our institution's prospective database. Between September 2003 and 2013, a total of 36 consecutive patients with AAA in association with Ca underwent surgical repair. Of these, 9 patients were excluded because the Ca treatment was performed at another service. Most of the patients were male (22) and the most frequent form of neoplasia was prostate Ca. Surgery for AAA repair was performed after the Ca treatment in 19 cases, before Ca treatment in 7 cases and concomitantly in 1 case. The intraoperative characteristics, treatment technique used, complications, patients' clinical evolution, and survival outcomes were analyzed. RESULTS: Endovascular aneurysm repair (EVAR) was used in 19 cases (70.4%) and conventional open repair (OR) in 8 cases (29.6%). Surgical treatment was uneventful in 19 cases, however, when present, postoperative complications occurred more frequently with EVAR (36.84% vs. 12.5%). There were no cases of death related to the aneurysm surgery. Most of the patients in both groups were alive at the end of the study. The probability of survival in our study was 65.8% at 3 years and 53% at 5 years, with no statistically significant difference between the EVAR and OR groups. The main cause of death was progression of the neoplastic disease. CONCLUSIONS: Patients who present Ca in association with AAA benefit from surgical treatment of both conditions, simultaneously or not. In these cases, it is important for the treatment to be individualized, and the disease of greater severity should be treated first. The endovascular and conventional open techniques were shown to be equivalent. PMID- 26541966 TI - Clinical Outcomes after Endovascular Treatment Failure in Patients with Femoropopliteal Occlusive Disease. AB - BACKGROUND: To analyze the clinical impact derived from endovascular treatment failure on patients with femoropopliteal occlusive disease (FPOD) regarding their preoperative clinical stage. METHODS: Retrospective review for primary endovascular procedures for FPOD from 2008 to 2013. Primary end point included clinical deterioration defined as acute limb ischemia (ALI) or clinical worsening by, at least, one Rutherford's classification category, related to procedure's failure (restenosis >70% or occlusion). RESULTS: Ninety procedures were analyzed in 85 patients, 87.8% operated due to critical limb ischemia. The lesion treated was classified as Trans-Atlantic Inter-Society Consensus (TASC)-A/B in 76.7%, with a mean length of 98.5 +/- 54 mm. Covered stent graft (SG) was used in 31.1% of the cases. Median follow-up was 14.5 months and treatment failure occurred in 33.3% of cases (n = 30, 9 restenosis and 21 occlusions). Clinical worsening was assessed in 40% of treatment failures and 6 of 21 (28.6%) presented as ALI. Twenty-two major adverse limb events (MALEs) were recorded and 8 major amputations. Regarding the type of stent, more occlusions were recorded on patients treated with SG compared with bare metal stent (39.3% vs. 16%; P = 0.02). However, no differences were found between groups regarding clinical worsening attributable to treatment failure (HR, 1.33; CI 95%, 0.5-3.5; P = 0.5). On multivariate analysis, TASC-C/D lesions (HR, 5.5; CI 95%, 2.3-13.3; P < 0.001) and female sex (HR, 4.9; CI 95%, 1.9-12.5; P = 0.001) behaved as significant predictors for failure and dual-antiplatelet therapy as a protective factor (HR, 0.3; CI 95%, 0.3-0.13; P = 0.03). No predictors were obtained regarding clinical worsening and occurrence of MALEs in our series. CONCLUSIONS: Patients with failure of endovascular procedures on FPOD appeared with clinical worsening in a no negligible number of cases in our sample regarding their preoperative clinical situation. Thus, we believe that endovascular treatment should be carefully deliberated. PMID- 26541967 TI - Gender Differences in Aortic Neck Morphology in Patients with Abdominal Aortic Aneurysms Undergoing Elective Endovascular Aneurysm Repair. AB - BACKGROUND: Previous studies have demonstrated that women tend to have adverse aortic neck morphology leading to exclusion of some women from undergoing endovascular aneurysm repair (EVAR). The objective of this study is to investigate differences in aortic neck morphology in men versus women, changes in the neck morphology and sac behavior after EVAR, and investigate how these features may influence outcomes. METHODS: We conducted a retrospective review of elective EVARs (2004-2013). We excluded patients who underwent elective EVAR with no postoperative imaging available and those patients with fenestrated repairs. Using TeraRecon and volumetric analysis, several features were investigated. These included percent thrombus, shape, length, angulation of the neck, and changes in neck and abdominal aortic aneurysm diameter. RESULTS: A total of 146 patients were found to meet inclusion criteria (115 men and 31 women) with similar baseline characteristics. Neck angulation was greater in women (23.9 degrees vs. 13.5 degrees ; P < 0.028). The percent thrombus in women was higher than men (35.4% vs. 31%; P < 0.02). Abdominal aneurysm's were smaller in women at 1 year (4.2 cm vs. 5.1 cm; P < 0.002), and secondary interventions were higher in men (11.3% vs. 0%; P < 0.05). Other features such as neck shape, changes in neck diameter, neck length, and percent oversizing of graft where not statistically different between genders. CONCLUSIONS: Gender differences in neck characteristics and changes in neck morphology do not appear to adversely affect EVAR outcomes. Longer follow-up is necessary to further assess whether these findings are clinically durable. PMID- 26541968 TI - Complication Rate after Carotid Endarterectomy Comparing Patch Angioplasty and Primary Closure. AB - BACKGROUND: Carotid endarterectomy (CEA) reduces the risk for stroke in patients with internal carotid artery stenosis. The optimal surgical technique remains subject of debate. Literature suggests patch angioplasty reduces complication risk. However, primary closure shortens cross-clamp times and eliminates graft specific complications. This study aimed to assess complication rate after CEA with selective patching. METHODS: A total of 213 consecutive CEAs over a 3-year period from January 5th, 2011 to December 19th, 2013 were retrospectively analyzed. Postoperative complications were evaluated within 1 month after surgery. RESULTS: Primary closure was used in 110 operations and patch angioplasty in 103 procedures. Primary closure was performed when the carotid artery had a diameter above 5 mm, when there was a high carotid bifurcation, and when the contralateral carotid artery was occluded. After primary closure, we found 4 (3.6%) complications: 2 (1.8%) bleeding and 2 (1.8%) cranial nerve damage. After patch angioplasty 5 (4.9%) complications occurred: 1 (1.0%) bleeding, 2 (1.9%) cranial nerve damage, 1 (1.0%) cerebrovascular event, and 1 (1.0%) cerebral hyperperfusion resulting in mortality. There was no higher complication risk after primary closure (P = 0.68). Clamp time was significantly longer when using patch angioplasty (P < 0.001). CONCLUSIONS: Primary closure appears to be an equivalent closure technique compared with patch angioplasty when used in selected patients. PMID- 26541969 TI - Clinical Features and Therapeutic Options for Isolated Visceral Artery Dissection. AB - BACKGROUND: The diagnosis of isolated visceral artery dissection (IVAD) has become more common with the increasing use of computed tomography angiography (CTA). We examined the presentation, treatment, and outcomes of patients with IVAD treated at our institution. METHODS: The records of 72 patients treated for IVAD between January 2010 and August 2014 were analyzed retrospectively. All were treated with antiplatelet or anticoagulant drugs after admission and were continued on oral aspirin for at least 1 year. Four asymptomatic and 52 symptomatic patients were managed conservatively with blood pressure control, bowel rest, fluid supplementation, and nutritional support. Two patients underwent open surgery because of hematochezia and 16 underwent endovascular bare metal stenting. RESULTS: Symptoms gradually resolved in those treated conservatively, and favorable arterial wall remodeling was observed in 16 patients. Twenty-one stents were implanted in 16 patients with superior mesenteric artery dissection; 3 patients required overlapping stents. During follow-up (range, 3-53 months), all patients were symptom-free, and there were no recurrences. Follow-up CTA of patients who underwent endovascular stenting demonstrated satisfactory stent and true lumen patency. CONCLUSIONS: IVAD is not uncommon. It occurs most frequently between the ages of 46 and 60 years and affects more men than women. A favorable outcome can be achieved in most of the patients with conservative management. Ischemic bowel necrosis is rare but requires open surgery. Endovascular bare-metal stenting is recommended when there is persistent abdominal pain, progression of the lesion, apparent stenosis of a true lumen compressed by a false lumen, or dilation of false lumen at a high risk of rupture. PMID- 26541970 TI - Open Mesenteric Interventions Are Equally Safe as Endovascular Interventions and Offer Better Midterm Patency for Chronic Mesenteric Ischemia. AB - BACKGROUND: Endovascular (EV) techniques are being advocated as the preferred method for mesenteric interventions because of their safety profile. However, midterm and long-term results are thought to be inferior to open interventions. We sought to compare our institutional experience with treatment of acute and chronic mesenteric ischemia (AMI and CMI, respectively) using EV and open techniques. METHODS: The medical records of open and EV mesenteric procedures performed at a single center were queried from 2002 to 2012. Demographic, perioperative, and follow-up data were extracted and analyzed. RESULTS: Thirty eight patients underwent EV mesenteric interventions, whereas 77 patients underwent open revascularization. The demographic and perioperative characteristics for patients were similar. Most EV procedures (89.2%) comprised stenting, whereas open procedures included 25 (32.1%) antegrade bypasses, 38 (48.7%) retrograde bypasses, 8 (10.3%) thromboembolectomies, and 7 (9%) transaortic endarterectomies. Postoperative complications, overall 30-day morbidity and mortality were not significantly different in the open and EV groups for AMI or CMI. Thirty-day mortality in AMI (n = 34) was 38.2% (EV: 45.5% vs. open: 34.8%; P = nonsignificant). There was no mortality in either group for CMI patients. Mean follow-up was much longer for the open procedures (34.9 vs. 12.7 months, P = 0.004). Primary and secondary patency rates were better for open revascularization for CMI patients. CONCLUSIONS: Open revascularizations are equally safe as EV interventions for AMI and CMI. Patency of open revascularization for CMI is better than EV procedures at midterm follow-up. PMID- 26541971 TI - Chronic Mesenteric Ischemia from Diaphragmatic Compression of the Celiac and Superior Mesenteric Arteries. AB - Median arcuate ligament syndrome (MALS) is caused by extrinsic compression of the celiac axis leading to postprandial epigastric abdominal pain, weight loss, and vomiting. The condition is most often identified in young women, and it is a controversial, unusual cause of chronic mesenteric ischemia. Rarely, the median arcuate ligament can compress the superior mesenteric artery (SMA) in addition to the celiac artery. We present a case of MALS in a young female patient with chronic abdominal pain resulting from external compression of not only the celiac artery but also the SMA. This patient was treated with release of the median arcuate ligament via an open retroperitoneal approach in addition to limited endarterectomy and patch angioplasty of the SMA. Preoperative and postoperative 3 dimensional computed tomographic angiographic images depict the lesions and their resolution after surgery. Few other cases of MALS caused by compression of both the celiac artery and SMA have ever been described in the literature. Although rare, it is important to keep the diagnosis of MALS in mind when encountering certain patients with chronic mesenteric ischemia of unclear etiology. Updated diagnostic work-up and treatment options for this condition are described. PMID- 26541972 TI - Statistical or biological significance? AB - Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield. PMID- 26541973 TI - Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. AB - Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells (ASCs) are a particularly attractive autologous cell source for various therapeutic purposes. ASCs retain a high proliferation capacity in vitro and have the ability to undergo extensive differentiation into multiple cell lineages. Moreover, ASCs secrete a wide range of growth factors that can stimulate tissue regeneration. Therefore, the clinical use of ASCs is feasible. However, the potential of ASCs differs depending on the donor's medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells. Therefore, to ensure the success of regenerative medicine, tissue engineering methods must be improved by the incorporation of factors that increase the proliferation and differentiation of stem/progenitor cells when autologous cells are used. Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, has recently been identified as a biological material that could be applied to tissue regeneration. Thus, co-transplantation of ASCs and PRP represents a promising novel approach for cell therapy in regenerative medicine. In this review, we describe the potential benefits of adding PRP to ASCs and preclinical and clinical studies of this approach in various medical fields. We also discuss the mechanisms of PRP action and future cell-based therapies using co-transplantation of ASCs and PRP. PMID- 26541974 TI - Enhanced Cross-Linking of Diazirine-Modified Sialylated Glycoproteins Enabled through Profiling of Sialidase Specificities. AB - Sialic-acid-mediated interactions play critical roles on the cell surface, providing an impetus for the development of methods to study this important monosaccharide. In particular, photo-cross-linking sialic acids incorporated onto cell surfaces have allowed covalent capture of transient interactions between sialic acids and sialic-acid-recognizing proteins via cross-linking. However, natural sialic acids also present on the cell surface compete with photo-cross linking sialic acids in binding events, limiting cross-linking yields. In order to improve the utility of one such photo-cross-linking sialic acid, SiaDAz, we examined a number of sialidases, enzymes that remove sialic acids from glycoconjugates, to find one that would cleave natural sialic acids but remain inactive toward SiaDAz. Using this sialidase, we improved SiaDAz-mediated cross linking of an antisialyl Lewis X antibody and of endoglin. This protocol can be applied generally to sialic-acid-mediated interactions and will facilitate identification of sialic acid binding partners. PMID- 26541975 TI - Relationships between self-reported ankle function and modulation of Hoffmann reflex in patients with chronic ankle instability. AB - OBJECTIVE: To examine relationships between self-reported ankle function and Hoffmann (H) reflex modulation during changes in body positions in patients with chronic ankle instability (CAI). DESIGN: Observational. SETTING: Laboratory. PARTICIPANTS: Thirty-one young adults with CAI (19 males, 12 females) participated. MAIN OUTCOME MEASURES: There were two subscales of Foot and Ankle Ability Measure (FAAM) to quantify self-reported ankle function during activities of daily living (ADL) and sports activities. Maximum H-reflexes (H-max) and motor waves (M-max) from soleus and fibularis longus were recorded while participants lied prone and stood in bipedal and unipedal stances. For each muscle, percent change scores in Hmax:Mmax ratios were calculated between each pair of positions: prone-to-bipedal, bipedal-to-unipedal, and prone-to-unipedal, and used as a measure of H-reflex modulation. Pearson correlation coefficients were calculated between FAAM and H-reflex modulation measures. RESULTS: There were significant correlations between: (1) FAAM-ADL and soleus prone-to-unipedal modulation (r = 0.384, p = 0.04), (2) FAAM-Sport and soleus prone-to-unipedal modulation (r = 0.505, p = 0.005), (3) FAAM-Sport and fibular bipedal-to-unipedal modulation (r = 0.377, p = 0.05), and (4) FAAM-Sport and fibular prone-to-unipedal modulation (r = 0.396, p = 0.04). CONCLUSIONS: CAI patients presented moderate, positive relationships between self-reported ankle function and H-reflex modulation during changes in body positions. PMID- 26541976 TI - Knowledge, attitudes and perceptions towards polio immunization among residents of two highly affected regions of Pakistan. AB - BACKGROUND: Despite the efforts of national and international organizations, polio has not been eradicated from Pakistan. The prevalence of polio in Pakistan is exceptional in global context. Quetta and Peshawar divisions are amongst the most affected regions hit by polio in Pakistan. This study was carried out to assess the knowledge, attitudes and perceptions towards polio immunization among residents of Quetta and Peshawar divisions in Pakistan. METHODS: A descriptive, cross-sectional study involving 768 participants was conducted from August to December, 2014 in Quetta and Peshawar divisions in Pakistan. Multistage sampling technique was used to draw a sample of residents from each division. A pre tested, self-administered questionnaire was used to collect the data from eligible participants. Descriptive and logistic regression analyses were used to express the results. RESULTS: A total of 38.8 % participants exhibited good knowledge about polio. Mean knowledge score of the participants was 7.35 +/- 2.54 (based on 15 knowledge questions). Older age (p < 0.001), low qualification (p < 0.05), rural locality (p < 0.05) and Quetta division (p < 0.001) were significantly associated with poor knowledge of polio. A large proportion of participants displayed negative attitudes towards polio immunization (84.8 %), with a mean score of 19.19 +/- 2.39 (based on 8 attitude statements). Lack of education (p < 0.001) and rural residence (p < 0.001) were significantly associated with the negative attitudes of participants towards polio immunization. False religious beliefs (39.06 %), lack of knowledge (33.7 %), fear of infertility by polio vaccines (32.16 %) and security issues (29.42 %) were reported by the participants as the main barriers towards polio immunization. CONCLUSION: The findings of this study showed poor knowledge and negative attitudes of participants towards polio immunizations. Religious beliefs and lack of knowledge about polio immunization were reported as the major barriers towards polio immunization. PMID- 26541978 TI - Health-related quality of life after robotic-assisted laparoscopic hysterectomy for women with endometrial cancer--A prospective cohort study. AB - OBJECTIVE: The aim of this prospective cohort study using patient-reported outcome measures (PROMs) was to detect short term changes in functioning, symptoms and health-related quality of life (HRQoL) after robotic-assisted laparoscopic hysterectomy (RALH) for endometrial cancer or atypical complex hyperplasia. METHODS/MATERIALS: A total of 139 women answered the EORTC C-30, EN 24 and EQ-5D-3L preoperatively (baseline) by face to face interview and again 1 week, 5 weeks and 4 months postoperatively by telephone interview. The women furthermore reported their level of activity compared to their habitual level in a diary during the first 5 weeks after surgery. RESULTS: We found a clinically relevant decrease in HRQoL after 1 week. At 5 weeks postoperatively, HRQoL was again at the preoperative level. Fatigue, pain, constipation, gastrointestinal symptoms, and appetite were all negatively affected 1 week postoperatively, but back to baseline level at 5 weeks. Ability to perform work or hobbies and change of taste were still affected at 5 weeks. CONCLUSIONS: HRQoL and postoperative symptoms were overall back to the preoperative level 5 weeks after RALH. These findings indicate fatigue, pain, constipation, gastrointestinal symptoms, appetite, ability to perform work and hobbies, change of taste and sexually related problems should be addressed in future research and in the pre- and postoperative care for women undergoing RALH. PMID- 26541979 TI - Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients. AB - OBJECTIVE: Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancer patients from a multi-ethnic cross-sectional cohort of Asian ovarian cancer patients from Malaysia. METHODS: From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancer patients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron-exon junctions and exonic sequences of BRCA1, BRCA2, PALB2 and TP53. RESULTS: BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancer patients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing. CONCLUSIONS: Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2. PMID- 26541980 TI - Risk-prediction model of severe postoperative complications after primary debulking surgery for advanced ovarian cancer. AB - OBJECTIVES: To refine models to predict surgical morbidity and 90-day mortality after primary debulking surgery (PDS) for advanced epithelial ovarian cancer (EOC). METHODS: Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/2/2003 and 12/30/2011 were included. Patient characteristics, intraoperative and postoperative outcomes, and vital status were abstracted. Complications were graded using the Accordion classification. Nomograms were generated based on multivariate modeling. RESULTS: 138 (22.3%) of the 620 patients who underwent PDS experienced a grade>=3 complication. Age (OR 1.21 per 10 years increase in age), BMI (OR 1.35 for BMI<25 kg/m2 versus reference, OR 2.83 for BMI>=40 kg/m2 versus reference), ASA score>=3 (OR 1.49), stage (OR 1.69 stage IV) and surgical complexity (OR 2.32 high complexity versus intermediate) were predictive of an accordion grade>=3 complication Within 90 days of surgery, 55 (8.9%) patients died. A multivariable model included age (OR 1.76 per 10 year increase in age), ASA score>=3 (OR 3.28), preoperative albumin<3.5 (OR 4.31), and BMI (OR 2.04 for BMI<25 kg/m2 versus reference, OR 3.64 for BMI>= 40 kg/m2 versus reference) was predictive of 90-day mortality. CONCLUSION: Using an independent cohort we report the importance of age, ASA score, preoperative albumin, FIGO stage, and surgical complexity, and BMI, to refine a prediction model for complications after PDS for advanced EOC. This information is useful in preoperative counseling and can be utilized to aid in patient-centered decision making and risk stratification. PMID- 26541977 TI - Genes and brain malformations associated with abnormal neuron positioning. AB - Neuronal positioning is a fundamental process during brain development. Abnormalities in this process cause several types of brain malformations and are linked to neurodevelopmental disorders such as autism, intellectual disability, epilepsy, and schizophrenia. Little is known about the pathogenesis of developmental brain malformations associated with abnormal neuron positioning, which has hindered research into potential treatments. However, recent advances in neurogenetics provide clues to the pathogenesis of aberrant neuronal positioning by identifying causative genes. This may help us form a foundation upon which therapeutic tools can be developed. In this review, we first provide a brief overview of neural development and migration, as they relate to defects in neuronal positioning. We then discuss recent progress in identifying genes and brain malformations associated with aberrant neuronal positioning during human brain development. PMID- 26541981 TI - Dual responsive polymeric nanoparticles prepared by direct functionalization of polylactic acid-based polymers via graft-from ring opening metathesis polymerization. AB - Polylactic acid (PLA) has found widespread use in plastics and in biomedical applications due to its biodegradability into natural benign products. However, PLA-based materials remain limited in usefulness due to difficulty of incorporating functional groups into the polymer backbone. In this paper, we report a strategy for PLA functionalization that establishes the preparation of highly derivatized materials in which ring opening metathesis polymerization (ROMP) is employed as a graft-from polymerization technique utilizing a norbornene-modified handle incorporated into the PLA backbone. As a demonstration of this new synthetic methodology, a PLA-derived nanoparticle bearing imidazole units protected with a photolabile group was prepared. The morphology of this material could be controllably altered in response to exposure of UV light or acidic pH as a stimulus. We anticipate that this graft-from approach to derivatization of PLA could find broad use in the development of modified, biodegradable PLA-based materials. PMID- 26541982 TI - A re-randomisation design for clinical trials. AB - BACKGROUND: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. METHODS: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used. RESULTS: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations. CONCLUSIONS: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations. PMID- 26541983 TI - Baseline monitoring of organic sunscreen compounds along South Carolina's coastal marine environment. AB - Organic ultraviolet filters (UV-F) are increasingly being used in personal care products to protect skin and other products from the damaging effects of UV radiation. In this study, marine water was collected monthly for approximately one year from six coastal South Carolina, USA sites and analyzed for the occurrence of seven organic chemicals used as UV filters (avobenzone, dioxybenzone, octocrylene, octinoxate, oxybenzone, padimate-o and sulisobenzone). The results were used to examine the relationship between beach use and the distribution of UV-F compounds along coastal South Carolina, USA. Five of the seven target analytes were detected in seawater along coastal South Carolina during this study. Dioxybenzone and sulisobenzone were not detected. The highest concentrations measured were >3700 ng octocrylene/L and ~2200 ng oxybenzone/L and beach use was greatest at this site; a local beach front park. Patterns in concentrations were assessed based on season and a measure of beach use. PMID- 26541984 TI - Carbon and nitrogen isotope ratios of juvenile winter flounder as indicators of inputs to estuarine systems. AB - Stable carbon and nitrogen isotope ratios were measured in young-of-the-year (YOY) winter flounder, Pseudopleuronectes americanus, collected from several Rhode Island, USA estuarine systems. These included three coastal lagoons, an estuarine river and Narragansett Bay. The delta(13)C trends observed along transects in several systems showed isotopically depleted terrestrial signals in the upper reaches of the estuaries. Significant differences (P<0.05) in delta(15)N were observed among all estuarine systems and these differences correlated (P<0.01) with human population densities in the watersheds. Although Narragansett Bay has a strong north-south gradient in nutrient concentrations this trend was not reflected in flounder delta(15)N. The northernmost station with the highest nutrient concentrations unexpectedly had significantly lower delta(15)N values. Depleted delta(15)N values at this nutrient-rich station may indicate that concentration-dependent fractionation needs to be considered when using nitrogen isotope ratios in biota to monitor anthropogenic nitrogen inputs in systems with high nitrogen loadings. PMID- 26541985 TI - Strategy for assessing impacts in ephemeral tropical seagrasses. AB - We investigated the phenology and spatial patterns in Halophila decipiens by assessing biomass, reproduction and seed density in ~400 grab samples collected across nine sites (8 to 14 m water depth) between June 2011 and December 2012. Phenology correlated with light climate which is governed by the summer monsoon (wet period). During the wet period, sedimentary seed banks prevailed, varying spatially at both broad and fine scales, presenting a source of propagules for re colonisation following the unfavourable growing conditions of the monsoon. Spatial patterns in H. decipiens biomass following monsoon conditions were highly variable within a landscape that largely comprised potential seagrass habitat. Management strategies for H. decipiens and similar transient species must recognise the high temporal and spatial variability of these populations and be underpinned by a framework that emphasises vulnerability assessments of different life stages instead of relying solely on thresholds for standing stock at fixed reference sites. PMID- 26541986 TI - Occurrence of diverse alkane hydroxylase alkB genes in indigenous oil-degrading bacteria of Baltic Sea surface water. AB - Formation of specific oil degrading bacterial communities in diesel fuel, crude oil, heptane and hexadecane supplemented microcosms of the Baltic Sea surface water samples was revealed. The 475 sequences from constructed alkane hydroxylase alkB gene clone libraries were grouped into 30 OPFs. The two largest groups were most similar to Pedobacter sp. (245 from 475) and Limnobacter sp. (112 from 475) alkB gene sequences. From 56 alkane-degrading bacterial strains 41 belonged to the Pseudomonas spp. and 8 to the Rhodococcus spp. having redundant alkB genes. Together 68 alkB gene sequences were identified. These genes grouped into 20 OPFs, half of them being specific only to the isolated strains. Altogether 543 diverse alkB genes were characterized in the brackish Baltic Sea water; some of them representing novel lineages having very low sequence identities with corresponding genes of the reference strains. PMID- 26541987 TI - Overdose prevention for prisoners in New York: a novel program and collaboration. AB - This is a brief report on the establishment of a new program in New York State prisons to prepare prisoners to avoid the increased risks of drug overdose death associated with the transition to the community by training them in overdose prevention and making available naloxone, a medication that quickly reverses the effects of an opioid overdose, to all prisoners as they re-enter the community. It is a milestone collaboration in the USA between public health, the correctional system, and a community-based harm reduction program in response to the growth of heroin and opioid analgesic use and related morbidity and mortality, working together to get naloxone into the hands of the people at high risk of overdosing and/or of witnessing an opioid overdose. PMID- 26541988 TI - Factors contributing to student nurses'/midwives' perceived competency in spiritual care. AB - BACKGROUND: The spiritual part of life is important to health, well-being and quality of life. Spiritual care is expected of nurses/midwives, but it is not clear how students can achieve competency in spiritual care at point of registration as required by regulatory bodies. AIM: To explore factors contributing to undergraduate nurses'/midwives' perceived competency in giving spiritual care. DESIGN: A pilot cross-sectional, multinational, correlational survey design. METHOD: Questionnaires were completed by 86% (n=531) of a convenience sample of 618 undergraduate nurses/midwives from six universities in four countries in 2010. Bivariate and multivariate analyses were performed. RESULTS: Differences between groups were small. Two factors were significantly related to perceived spiritual care competency: perception of spirituality/spiritual care and student's personal spirituality. Students reporting higher perceived competency viewed spirituality/spiritual care broadly, not just in religious terms. This association between perceived competency and perception of spirituality is a new finding not previously reported. Further results reinforce findings in the literature that own spirituality was a strong predictor of perceived ability to provide spiritual care, as students reporting higher perceived competency engaged in spiritual activities, were from secular universities and had previous healthcare experience. They were also religious, practised their faith/belief and scored highly on spiritual well-being and spiritual attitude/involvement. CONCLUSIONS: The challenge for nurse/midwifery educators is how they might enhance spiritual care competency in students who are not religious and how they might encourage students who hold a narrow view of spirituality/spiritual care to broaden their perspective to include the full range of spiritual concerns that patients/clients may encounter. Statistical models created predicted factors contributing to spiritual care competency to some extent but the picture is complex requiring further investigation involving a bigger and more diverse longitudinal sample. PMID- 26541989 TI - Budesonide Multi-matrix for the Treatment of Patients with Ulcerative Colitis. AB - Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder in which patients cycle between active disease and remission. Budesonide multi-matrix (MMX) is an oral second-generation corticosteroid designed to deliver active drug throughout the colon. In pharmacokinetic studies, the mean relative absorption of budesonide in the region between the ascending colon and the descending/sigmoid colon was 95.9 %. In 2 identically designed, phase 3 studies (CORE I and II), budesonide MMX 9 mg once daily was efficacious and well tolerated for induction of remission of mild to moderate UC. Clinical and endoscopic remission rates were 17.9 % (CORE I) and 17.4 % (CORE II) for budesonide MMX 9 mg compared with 7.4 and 4.5 %, respectively, with placebo (p < 0.05, budesonide MMX 9 mg vs. placebo in both studies), 12.1 % with mesalamine 2.4 g, and 12.6 % with budesonide controlled ileal release capsules 9 mg. A 12-month maintenance therapy study suggested that budesonide MMX 6 mg may prolong time to clinical relapse: Median time was >1 year with budesonide MMX 6 mg versus 181 days (p = 0.02) with placebo; however, further studies are needed. In the CORE studies, budesonide MMX exhibited a favorable safety profile; the majority of adverse events were mild or moderate in intensity, and serious adverse events were uncommon. Furthermore, rates of potential glucocorticoid-related adverse events were comparable across treatment groups. The long-term (12-month) safety of budesonide MMX appears to be comparable with placebo. Data support budesonide MMX in the management algorithm of UC. PMID- 26541990 TI - Self-Limited Sepsis Syndrome Following Fecal Microbiota Therapy for Refractory C. difficile Infection. PMID- 26541991 TI - Microwave Ablation for the Treatment of Hypersplenism: Short Waves, Low Cost, Big Results. PMID- 26541993 TI - Competency in ECG Interpretation Among Medical Students. AB - BACKGROUND: Electrocardiogram (ECG) is commonly used in diagnosis of heart diseases, including many life-threatening disorders. We aimed to assess skills in ECG interpretation among Polish medical students and to analyze the determinants of these skills. MATERIAL AND METHODS: Undergraduates from all Polish medical schools were asked to complete a web-based survey containing 18 ECG strips. Questions concerned primary ECG parameters (rate, rhythm, and axis), emergencies, and common ECG abnormalities. Analysis was restricted to students in their clinical years (4th-6th), and students in their preclinical years (1st-3rd) were used as controls. RESULTS: We enrolled 536 medical students (females: n=299; 55.8%), aged 19 to 31 (23+/-1.6) years from all Polish medical schools. Most (72%) were in their clinical years. The overall rate of good response was better in students in years 4th-5th than those in years 1st-3rd (66% vs. 56%; p<0.0001). Competency in ECG interpretation was higher in students who reported ECG self learning (69% vs. 62%; p<0.0001) but no difference was found between students who attended or did not attend regular ECG classes (66% vs. 66%; p=0.99). On multivariable analysis (p<0.0001), being in clinical years (OR: 2.45 [1.35-4.46] and self-learning (OR: 2.44 [1.46-4.08]) determined competency in ECG interpretation. CONCLUSIONS: Polish medical students in their clinical years have a good level of competency in interpreting the primary ECG parameters, but their ability to recognize ECG signs of emergencies and common heart abnormalities is low. ECG interpretation skills are determined by self-education but not by attendance at regular ECG classes. Our results indicate qualitative and quantitative deficiencies in teaching ECG interpretation at medical schools. PMID- 26541992 TI - Outcomes of Propofol Sedation During Emergency Endoscopy Performed for Upper Gastrointestinal Bleeding. AB - BACKGROUND: Although propofol-based sedation can be used during emergency endoscopy for upper gastrointestinal bleeding (UGIB), there is a potential risk of sedation-related adverse events, especially in patients with variceal bleeding. AIM: We compared adverse events related to propofol-based sedation during emergency endoscopy between patients with non-variceal and variceal bleeding. METHODS: Clinical records of patients who underwent emergency endoscopy for UGIB under sedation were reviewed. Adverse events, including shock, hypoxia, and paradoxical reaction, were compared between the non-variceal and variceal bleeding groups. RESULTS: Of 703 endoscopies, 539 and 164 were performed for non variceal and variceal bleeding, respectively. Shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding (12.2 vs. 3.5%, P < 0.001). All patients except one recovered from shock after normal saline hydration, and emergency endoscopy could be finished without interruption in most cases. The incidence of hypoxia and paradoxical reaction did not differ based on the source of bleeding (non-variceal bleeding vs. variceal bleeding: hypoxia, 3.5 vs. 1.8%, P = 0.275; paradoxical reaction interfering with the procedure, 4.1 vs. 5.5%, P = 0.442). CONCLUSIONS: Although shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding, most cases could be controlled without procedure interruption. Paradoxical reaction, rather than shock or hypoxia, was the most common cause of procedure interruption in patients with variceal bleeding, but the rate did not differ between patients with non-variceal and variceal bleeding. PMID- 26541994 TI - Relationship inference based on DNA mixtures. AB - Today, there exists a number of tools for solving kinship cases. But what happens when information comes from a mixture? DNA mixtures are in general rarely seen in kinship cases, but in a case presented to the Norwegian Institute of Public Health, sample DNA was obtained after a rape case that resulted in an unwanted pregnancy and abortion. The only available DNA from the fetus came in form of a mixture with the mother, and it was of interest to find the father of the fetus. The mother (the victim), however, refused to give her reference data and so commonly used methods for paternity testing were no longer applicable. As this case illustrates, kinship cases involving mixtures and missing reference profiles do occur and make the use of existing methods rather inconvenient. We here present statistical methods that may handle general relationship inference based on DNA mixtures. The basic idea is that likelihood calculations for mixtures can be decomposed into a series of kinship problems. This formulation of the problem facilitates the use of kinship software. We present the freely available R package relMix which extends on the R version of Familias. Complicating factors like mutations, silent alleles, and theta-correction are then easily handled for quite general family relationships, and are included in the statistical methods we develop in this paper. The methods and their implementations are exemplified on the data from the rape case. PMID- 26541995 TI - What controls the expression of the core-1 (Thomsen-Friedenreich) glycotope on tumor cells? AB - Malignant transformation is tightly connected with changes in the glycosylation of proteins and lipids, which in turn are contributing to the invasive and metastatic behavior of tumor cells. One example of such changes is demasking of the otherwise hidden core-1 structure, also known as Thomsen-Friedenreich antigen, which is a highly tumor-specific glycotope and potentially a cancer stem cell marker. This review summarizes what is known about the mechanism(s) of its expression on tumor cells. New data reveal a close connection between tumor metabolism and Golgi function. Based on these data, we suggest that the expression of this antigen is also a marker of aerobic glycolysis. PMID- 26541996 TI - Gangliosides in breast cancer: new perspectives. AB - Gangliosides are essential compounds of the plasma membrane involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly supported by the glycan moiety, and changes in the structure of gangliosides occur under pathological conditions including cancers. With progress in mass spectrometric analysis of gangliosides, the role of gangliosides in breast cancer progression was recently demonstrated. In this review, we summarize current knowledge on the biosynthesis of gangliosides and of the role of disialogangliosides in triple negative breast cancer progression and metastasis. New perspectives in breast cancer therapy targeting gangliosides are also discussed. PMID- 26541997 TI - Hypotheses of the origin of natural antibodies: a glycobiologist's opinion. AB - It is generally accepted that the generation of antibodies proceeds due to immunization of an organism by alien antigens, and the level and affinity of antibodies are directly correlated to the presence of immunogen. At the same time, vast experimental material has been obtained providing evidence of antibodies whose level remains unchanged and affinity is constant during a lifetime. In contrast to the first, adaptive immunoglobulins, the latter are named natural antibodies (nAbs). The nAbs are produced by B1 cells, whereas adaptive Abs are produced by B2. This review summarizes general data on nAbs and presents in more detail data on antigens of carbohydrate origin. Hypotheses on the origin of nAbs and their activation mechanisms are discussed. We present our thoughts on this matter supported by our experimental data on nAbs to glycans. PMID- 26541998 TI - Exploiting natural anti-carbohydrate antibodies for therapeutic purposes. AB - Natural anti-carbohydrate antibodies (NAbC) are antibodies that target glycans and are continuously produced without apparent external antigen stimulation. Clinically, NAbC are recognized by the adverse reactions to ABO mismatched blood transfusions or organ transplantation and the rejection of xenografts. These clinical effects do not reflect the biological functions of NAbC. However, they launch the possibility of using NAbC for boosting immunity in different clinical settings by means of: 1) expression of glycan antigens in elements that do not hold them to allow the binding and reactivity of existing NAbC; 2) removal of existing NAbC; 3) manipulation of the glycosylation pattern of NAbC. PMID- 26541999 TI - Specificity of human galectins on cell surfaces. AB - Galectins are beta-galactoside-binding proteins sharing homology in amino acid sequence of their carbohydrate-recognition domain. Their carbohydrate specificity outside cells has been studied previously. The main conclusion of these studies was that several levels of glycan ligand recognition exist for galectins: (i) disaccharide Galbeta1-4GlcNAc (LN, N-acetyllactosamine) binds stronger than beta galactopyranose; (ii) substitution at O-2 and O-3 of galactose residue as well as core fragments ("right" from GlcNAc) provides significant increase in affinity; (iii) similarly glycosylated proteins can differ significantly in affinity to galectins. Information about the natural cellular receptors of galectins is limited. Until recently, it was impossible to study specificity of cell-bound galectins. A model based on controlled incorporation of a single protein into glycocalyx of cells and subsequent interaction of loaded cells with synthetic glycoprobes measured by flow cytometry made this possible recently. In this review, data about glycan specificity of proto-, chimera-, and tandem-repeat type galectins on the cell surface are systematized, and comparative analysis of the results with data on specificity of galectins in artificial systems was performed. The following conclusions from these studies were made: (i) cellular galectins have practically no ability to bind disaccharide LNn, but display affinity to 3'-substituted oligolactosamines and oligomers LNn; (ii) tandem repeat type galectins recognize another disaccharide, namely Galbeta1-3GlcNAc (Le(c)); (iii) on the cell surface, tandem-repeat type galectins conserve the ability to display high affinity to blood group antigens of ABH system; (iv) in general, when galectins are immersed into glycocalyx, they are more selective regarding glycan interactions. Thus, we conclude that competitive interaction of galectins with cell microenvironment (endogenous cell glycans) is the main factor providing selectivity of galectins in vivo. PMID- 26542000 TI - Synthetic glycolipid-like constructs as tools for glycobiology research, diagnostics, and as potential therapeutics. AB - Function-spacer-lipid (FSL) constructs are amphiphilic molecules that are able to disperse in water and then self-assemble into cell membranes or onto solid surfaces. Modification of a biological or non-biological surface is very easy and achieved by simple contact of the surface with an appropriately buffered solution containing one or more FSLs. When the functional head group of the FSL is a glycan, glycan modified surfaces can be rapidly formed. Once cells, viruses, or solid surfaces are FSL modified with either simple or complex glycans, they can be used in vitro and/or in vivo to measure interactions with cells, viruses, antibodies, and lectins. FSLs have already been used in a variety of techniques including antibody specificity mapping, antibody/toxin neutralization, diagnostic assays, immune system manipulation, and animal modeling of transfusion reactions. FSLs offer the easiest and fastest method available to achieve a glycan-modified surface. PMID- 26542001 TI - What adaptive changes in hemagglutinin and neuraminidase are necessary for emergence of pandemic influenza virus from its avian precursor? AB - Wild ducks serve as the primary host for numerous and various influenza type A viruses. Occasionally, viruses from this reservoir can be transferred to other host species and cause outbreaks of influenza in fowl, swine, and horses, as well as result in novel human pandemics. Cellular tropism and range of susceptible host species are determined by interaction between virus and receptor molecules on cells. Here we discuss modern data regarding molecular features underlying interactions of influenza viruses with cellular receptors as well as a role for receptor specificity in interspecies transmission. By analyzing the earliest available pandemic influenza viruses (1918, 1957, 1968, 2009), we found that hemagglutinin reconfigured to recognize 2-6 sialic acid-containing receptors in the human upper airway tract together with altered enzymatic activity of neuraminidase necessary for maintaining functional balance with hemagglutinin are responsible for effective spread of influenza viruses in human populations. Resistance to low pH also contributes to this. Thus, a combination of such parameters makes it possible that influenza viruses give rise to novel pandemics. PMID- 26542002 TI - Plant oligosaccharides - outsiders among elicitors? AB - This review substantiates the need to study the plant oligoglycome. The available information on oligosaccharins - physiologically active fragments of plant cell wall polysaccharides - is summarized. The diversity of such compounds in chemical composition, origin, and proved biological activity is highlighted. At the same time, plant oligosaccharides can be considered as outsiders among elicitors of various natures in research intensity of recent decades. This review discusses the reasons for such attitude towards these regulators, which are largely connected with difficulties in isolation and identification. Together with that, approaches are suggested whose potentials can be used to study oligosaccharins. The topics of oligosaccharide metabolism in plants, including the ways of formation, transport, and inactivation are presented, together with data on biological activity and interaction with plant hormones. The current viewpoints on the mode of oligosaccharin action - perception, signal transduction, and possible "targets" - are considered. The potential uses of such compounds in medicine, food industry, agriculture, and biotechnology are discussed. PMID- 26542003 TI - O-antigen modifications providing antigenic diversity of Shigella flexneri and underlying genetic mechanisms. AB - O-Antigens (O-specific polysaccharides) of Shigella flexneri, a primary cause of shigellosis, are distinguished by a wide diversity of chemical modifications following the oligosaccharide O-unit assembly. The present review is devoted to structural, serological, and genetic aspects of these modifications, including O acetylation and phosphorylation with phosphoethanolamine that have been identified recently. The modifications confer the host with specific immunodeterminants (O-factors or O-antigen epitopes), which accounts for the antigenic diversity of S. flexneri considered as a virulence factor of the pathogen. Totally, 30 O-antigen variants have been recognized in these bacteria, the corresponding O-factors characterized using specific antibodies, and a significant extension of the serotyping scheme of S. flexneri on this basis is suggested. Multiple genes responsible for the O-antigen modifications and the resultant serotype conversions of S. flexneri have been identified. The genetic mechanisms of the O-antigen diversification by acquisition of mobile genetic elements, including prophages and plasmids, followed occasionally by gene mobilization and inactivation have been revealed. These findings further our understanding of the genetics and antigenicity of S. flexneri and assist control of shigellosis. PMID- 26542004 TI - Tissue-specific rhamnogalacturonan I forms the gel with hyperelastic properties. AB - Rhamnogalacturonans I are complex pectin polysaccharides extremely variable in structure and properties and widely represented in various sources. The complexity and diversity of the structure of rhamnogalacturonans I are the reasons for the limited information about the properties and supramolecular organization of these polysaccharides, including the relationship between these parameters and the functions of rhamnogalacturonans I in plant cells. In the present work, on the example of rhamnogalacturonan I from flax gelatinous fibers, the ability of this type of pectic polysaccharides to form at physiological concentrations hydrogels with hyperelastic properties was revealed for the first time. According to IR spectroscopy, water molecules are more tightly retained in the gelling rhamnogalacturonan I from flax fiber cell wall in comparison with the non-gelling rhamnogalacturonan I from primary cell wall of potato. With increase in strength of water binding by rhamnogalacturonan I, there is an increase in elastic modulus and decrease in Poisson's ratio of gel formed by this polysaccharide. The model of hyperelastic rhamnogalacturonan I capture by laterally interacting cellulose microfibrils, constructed using the finite element method, confirmed the suitability of rhamnogalacturonan I gel with the established properties for the function in the gelatinous cell wall, allowing consideration of this tissue- and stage-specific pectic polysaccharide as an important factor in creation of gelatinous fiber contractility. PMID- 26542005 TI - Influence of fucoidans and their derivatives on antitumor and phagocytic activity of human blood leucocytes. AB - The immunotropic activity of structurally different fucoidans and their derivatives towards isolated immune blood cells, effectors of innate immune system, was studied. The most potent effect was observed for high molecular weight fucoidan CF from the alga Chordaria flagelliformis, whose backbone is built of (1->3)-linked units of alpha-L-fucopyranose, and branches included residues of alpha-D-glucuronic acid and alpha-L-fucofuranose. This compound at the concentration of 0.05 mg/ml potentiated phagocytosis of Saccharomyces cerevisiae and Lactobacillus acidophilus by neutrophils, increasing relative quantity of phagocytes as well as their effectiveness. Along with this, 14% increase in the concentration of membrane-bound integrin CD11c molecules was observed. The systemic effect of CF at the dose of 0.01 mg/mouse i.p. led to potentiation of cytotoxic activity of spleen mononuclear leucocytes towards melanoma cells of line B16 by 1.9-fold and towards chronic myelogenous leukemia cells of line K-562 by 1.7-fold. These results indicate that fucoidan CF can stimulate anti-infective and antitumor activity of effectors of the innate immune system via CD11c integrins. PMID- 26542006 TI - High-throughput glycomics: optimization of sample preparation. AB - Glycosylation affects structure, folding, and function of numerous proteins. Aberrant glycosylation has been shown to be associated with different diseases. A wide range of analytical methods is available for glycan analysis of antibodies (mainly IgG), but analysis of plasma glycans is less established due to additional challenges encountered with higher complexity of the sample. Here we describe development and optimization of a high-throughput sample preparation method for hydrophilic interaction liquid chromatography and ultra-performance liquid chromatography analysis of plasma N-glycans. Clean-up of labeled glycans was found to be the largest source of variation, and we tested cellulose, silica gel, Bio-Gel, and hydrophilic GHP filter as stationary phases for solid-phase extraction. All stationary phases were shown to be suitable for purification of labeled glycans, but GHP filter plate in combination with cold 96% acetonitrile had the highest reproducibility and was easiest to work with. The method was further optimized with Plackett-Burman screening design and validated in terms of analysis of major step variation and between-day and between-person variation. The developed method is fast, cost-effective, and easy to perform, and it has very good reproducibility during long period of time, enabling the detection of biological variability of the plasma N-glycome. PMID- 26542007 TI - X-ray reflectivity and grazing incidence diffraction studies of interaction between human adhesion/growth-regulatory galectin-1 and DPPE-GM1 lipid monolayer at an air/water interface. AB - The specific interaction of ganglioside GM1 with the homodimeric (prototype) endogenous lectin galectin-1 triggers growth regulation in tumor and activated effector T cells. This proven biorelevance directed interest to studying association of the lectin to a model surface, i.e. a 1,2-dihexadecanoyl-sn glycero-3-phosphoethanolamine/ganglioside GM1 (80 : 20 mol%) monolayer, at a bioeffective concentration. Surface expansion by the lectin insertion was detected at a surface pressure of 20 mN/m. On combining the methods of grazing incidence X-ray diffraction and X-ray reflectivity, a transient decrease in lipid ordered phase of the monolayer was observed. The measured electron density distribution indicated that galectin-1 is oriented with its long axis in the surface plane, ideal for cis-crosslinking. The data reveal a conspicuous difference to the way the pentameric lectin part of the cholera toxin, another GM1-specific lectin, is bound to the monolayer. They also encourage further efforts to monitor effects of structurally different members of the galectin family such as the functionally antagonistic chimera-type galectin-3. PMID- 26542008 TI - En1 directs superior olivary complex neuron positioning, survival, and expression of FoxP1. AB - Little is known about the genetic pathways and transcription factors that control development and maturation of central auditory neurons. En1, a gene expressed by a subset of developing and mature superior olivary complex (SOC) cells, encodes a homeodomain transcription factor important for neuronal development in the midbrain, cerebellum, hindbrain and spinal cord. Using genetic fate-mapping techniques, we show that all En1-lineal cells in the SOC are neurons and that these neurons are glycinergic, cholinergic and GABAergic in neurotransmitter phenotype. En1 deletion does not interfere with specification or neural fate of these cells, but does cause aberrant positioning and subsequent death of all En1 lineal SOC neurons by early postnatal ages. En1-null cells also fail to express the transcription factor FoxP1, suggesting that FoxP1 lies downstream of En1. Our data define important roles for En1 in the development and maturation of a diverse group of brainstem auditory neurons. PMID- 26542009 TI - ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate. AB - The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment. PMID- 26542010 TI - Dynamin-mediated endocytosis is required for tube closure, cell intercalation, and biased apical expansion during epithelial tubulogenesis in the Drosophila ovary. AB - Most metazoans are able to grow beyond a few hundred cells and to support differentiated tissues because they elaborate multicellular, epithelial tubes that are indispensable for nutrient and gas exchange. To identify and characterize the cellular behaviors and molecular mechanisms required for the morphogenesis of epithelial tubes (i.e., tubulogenesis), we have turned to the D. melanogaster ovary. Here, epithelia surrounding the developing egg chambers first pattern, then form and extend a set of simple, paired, epithelial tubes, the dorsal appendage (DA) tubes, and they create these structures in the absence of cell division or cell death. This genetically tractable system lets us assess the relative contributions that coordinated changes in cell shape, adhesion, orientation, and migration make to basic epithelial tubulogenesis. We find that Dynamin, a conserved regulator of endocytosis and the cytoskeleton, serves a key role in DA tubulogenesis. We demonstrate that Dynamin is required for distinct aspects of DA tubulogenesis: DA-tube closure, DA-tube-cell intercalation, and biased apical-luminal cell expansion. We provide evidence that Dynamin promotes these processes by facilitating endocytosis of cell-cell and cell-matrix adhesion complexes, and we find that precise levels and sub-cellular distribution of E Cadherin and specific Integrin subunits impact DA tubulogenesis. Thus, our studies identify novel morphogenetic roles (i.e., tube closure and biased apical expansion), and expand upon established roles (i.e., cell intercalation and adhesion remodeling), for Dynamin in tubulogenesis. PMID- 26542011 TI - Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. AB - Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1(+) progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema. PMID- 26542013 TI - Adolescents with Special Needs: Clinical Challenges in Reproductive Health Care. AB - Adolescents with special needs have unique reproductive health care needs related to their physical and cognitive issues. This review discusses some of the most common concerns that are encountered in clinical practice, as the clinician will partner with the adolescent and her family to guide her through the pubertal transition and to help navigate the risks and rights of reproduction. Families often seek anticipatory guidance before menarche on menstrual hygiene, abuse risk and sexuality and can be reassured that most teens with special needs do very well with menstruation. The clinician needs to evaluate the teenager's reproductive knowledge as well her risk for abuse and coercion and her ability to consent to sexual activity, if she requests contraception. Menstrual management is mostly based on the impact of the menstrual cycles on the teenager's life and activities. The adolescents may have a decreased ability to tolerate menses or pain, or experience changes in seizure pattern or altered mood. Hormonal treatment is often used to assist with menstrual hygiene, cyclical mood changes or dysmenorrhea. The goal of treatment can be complete amenorrhea, alleviate pain or regulate and decrease menstrual flow. The unique risks and benefits of hormonal treatment for this special population are highlighted. PMID- 26542012 TI - Primary cilia are critical for Sonic hedgehog-mediated dopaminergic neurogenesis in the embryonic midbrain. AB - Midbrain dopaminergic (mDA) neurons modulate various motor and cognitive functions, and their dysfunction or degeneration has been implicated in several psychiatric diseases. Both Sonic Hedgehog (Shh) and Wnt signaling pathways have been shown to be essential for normal development of mDA neurons. Primary cilia are critical for the development of a number of structures in the brain by serving as a hub for essential developmental signaling cascades, but their role in the generation of mDA neurons has not been examined. We analyzed mutant mouse lines deficient in the intraflagellar transport protein IFT88, which is critical for primary cilia function. Conditional inactivation of Ift88 in the midbrain after E9.0 results in progressive loss of primary cilia, a decreased size of the mDA progenitor domain, and a reduction in mDA neurons. We identified Shh signaling as the primary cause of these defects, since conditional inactivation of the Shh signaling pathway after E9.0, through genetic ablation of Gli2 and Gli3 in the midbrain, results in a phenotype basically identical to the one seen in Ift88 conditional mutants. Moreover, the expansion of the mDA progenitor domain observed when Shh signaling is constitutively activated does not occur in absence of Ift88. In contrast, clusters of Shh-responding progenitors are maintained in the ventral midbrain of the hypomorphic Ift88 mouse mutant, cobblestone. Despite the residual Shh signaling, the integrity of the mDA progenitor domain is severely disturbed, and consequently very few mDA neurons are generated in cobblestone mutants. Our results identify for the first time a crucial role of primary cilia in the induction of mDA progenitors, define a narrow time window in which Shh-mediated signaling is dependent upon normal primary cilia function for this purpose, and suggest that later Wnt signaling dependent events act independently of primary cilia. PMID- 26542014 TI - Teaching Trainees to Deliver Adolescent Reproductive Health Services. AB - STUDY OBJECTIVE: Delivery of reproductive services to adolescents varies according to specialty and has been linked to differences in clinical training. Few studies have explored how different specialties' graduate medical education (GME) programs prepare providers to deliver adolescent reproductive services. We explored the perceptions of resident physicians regarding their training in delivering adolescent reproductive health services. DESIGN: Between November 2008 and February 2009, 9 focus groups were conducted with graduate medical trainees in 3 specialties that routinely care for adolescents. The semistructured discussions were audio-recorded, transcribed, and analyzed using an inductive approach to content analysis. SETTING: Large, urban academic medical center in Pittsburgh, Pennsylvania. PARTICIPANTS: Fifty-four resident trainees in pediatrics, family medicine, and obstetrics/gynecology. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Trainees' perspectives regarding the didactic teaching and clinical training in providing adolescent reproductive services. RESULTS: Five themes emerged, reflecting trainees' beliefs regarding the best practices in which GME programs can engage to ensure that trainees graduate with the belief that they are competent and will be comfortable delivering adolescent reproductive services. Trainees believed programs need to: (1) provide didactic lectures and diverse inpatient and outpatient clinical experiences; (2) have faculty preceptors skilled in providing and supervising adolescent reproductive services; (3) teach skills for engaging adolescents in clinical assessments and decision-making; (4) train providers to navigate confidentiality issues with adolescents and caregivers; and (5) provide infrastructure and resources for delivering adolescent reproductive services. CONCLUSION: The 3 specialties differed in how well each of the 5 best practices were reportedly addressed during GME training. Policy recommendations are provided. PMID- 26542015 TI - Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters. AB - BACKGROUND/PURPOSE: Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45 degrees C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients treated with reirradiation+hyperthermia (reRT+HT) in the AMC(n=301) and the BVI(n=113), from 1982 to 2005 were retrospectively analyzed for treatment response, locoregional control (LC) and prognostic factors for LC and toxicity. PATIENTS/METHODS: All patients received previous irradiation (median 50 Gy). reRT consisted of 8 * 4 Gy-2/week (AMC) or 12 * 3 Gy-4/week (BVI). Hyperthermia was added once (AMC)/twice (BVI) a week. RESULTS: Overall clinical response rate was 86%. The 3-year LC rate was 25%. The number of recurrence episodes, distant metastases (DM), tumor site, tumor size, time to recurrence and treatment year were significant for LC. Acute ? grade 3 toxicity occurred in 24% of patients. Actuarial late ? grade 3 toxicity was 23% at 3 years. In multivariable analysis reRT fraction dose was significantly related to late ? grade 3 toxicity. CONCLUSION: reRT+HT is an effective curative and palliative treatment option for patients with irresectable locoregional recurrent breast cancer in previously irradiated area. Early referral, treatment of chest wall recurrences ? 5 cm in the absence of distant metastases, provided the highest local control rates. The cumulative effects of past and present treatments should be accounted for by adjusting treatment protocol to minimize toxicity. PMID- 26542016 TI - Compilation of basal metabolic and blood perfusion rates in various multi compartment, whole-body thermoregulation models. AB - The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 +/- 2 W, and in the BCO, it was 8 % with a mean of 4.70 +/- 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: +/-7.8 % BMR and +/-5.9 % BBPR) and in the combined head (head, face, and neck +/-9.9 % BMR and +/-10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (+/-117 %), followed by the BBPR in the arms (+/-61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data. PMID- 26542017 TI - Effect of two sweating simulation methods on clothing evaporative resistance in a so-called isothermal condition. AB - The effect of sweating simulation methods on clothing evaporative resistance was investigated in a so-called isothermal condition (T manikin = T a = T r ). Two sweating simulation methods, namely, the pre-wetted fabric "skin" (PW) and the water supplied sweating (WS), were applied to determine clothing evaporative resistance on a "Newton" thermal manikin. Results indicated that the clothing evaporative resistance determined by the WS method was significantly lower than that measured by the PW method. In addition, the evaporative resistances measured by the two methods were correlated and exhibited a linear relationship. Validation experiments demonstrated that the empirical regression equation showed highly acceptable estimations. The study contributes to improving the accuracy of measurements of clothing evaporative resistance by means of a sweating manikin. PMID- 26542018 TI - Morphology of pedestrian roads and thermal responses during summer, in the urban area of Bucheon city, Korea. AB - The purpose of this study was to elucidate the effect of urban morphology representing sky view factor (SVF) on urban microclimate and on human thermal responses. The physical environments and the changes in body temperatures as well as psychological responses were investigated in summer in Bucheon, Korea. The dry bulb temperature ranged from 31.5 degrees C at SVF 0.082 site to 35.7 degrees C at SVF 0.922 site. Most of the environmental elements were statistically correlated to the SVF: the dry bulb temperature R (2) = 0.602, UVB R (2) = 0.556 and the illumination level R (2) = 0.609. The mean skin temperature increased up to 36.0 degrees C at the SVF 0.940 site and decreased to 33.9 degrees C at the SVF 0.082 site. The mean skin temperature was statistically correlated to the SVF (p = 0.005). However, the core body temperature was not correlated to SVF because of time delay effect to the previously exposed thermal environment. In the investigation of thermal acceptability, only 5 % of subjects were dissatisfied with the road that was covered with plentiful trees; in contrast, approximately 50 % of subjects were dissatisfied with the road with poor solar obstacles in the summer. The thermal stress was affected by the urban morphology, and the plentiful urban greening improved thermal comfort. PMID- 26542019 TI - P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2. AB - Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell-matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca(2+) signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions. PMID- 26542020 TI - The selective inhibition of protein phosphatase-1 results in mitotic catastrophe and impaired tumor growth. AB - The serine/threonine protein phosphatase-1 (PP1) complex is a key regulator of the cell cycle. However, the redundancy of PP1 isoforms and the lack of specific inhibitors have hampered studies on the global role of PP1 in cell cycle progression in vertebrates. Here, we show that the overexpression of nuclear inhibitor of PP1 (NIPP1; also known as PPP1R8) in HeLa cells culminated in a prometaphase arrest, associated with severe spindle-formation and chromosome congression defects. In addition, the spindle assembly checkpoint was activated and checkpoint silencing was hampered. Eventually, most cells either died by apoptosis or formed binucleated cells. The NIPP1-induced mitotic arrest could be explained by the inhibition of PP1 that was titrated away from other mitotic PP1 interactors. Consistent with this notion, the mitotic-arrest phenotype could be rescued by the overexpression of PP1 or the inhibition of the Aurora B kinase, which acts antagonistically to PP1. Finally, we demonstrate that the overexpression of NIPP1 also hampered colony formation and tumor growth in xenograft assays in a PP1-dependent manner. Our data show that the selective inhibition of PP1 can be used to induce cancer cell death through mitotic catastrophe. PMID- 26542021 TI - A direct interaction between fascin and microtubules contributes to adhesion dynamics and cell migration. AB - Fascin is an actin-binding and bundling protein that is highly upregulated in most epithelial cancers. Fascin promotes cell migration and adhesion dynamics in vitro and tumour cell metastasis in vivo. However, potential non-actin bundling roles for fascin remain unknown. Here, we show for the first time that fascin can directly interact with the microtubule cytoskeleton and that this does not depend upon fascin-actin bundling. Microtubule binding contributes to fascin-dependent control of focal adhesion dynamics and cell migration speed. We also show that fascin forms a complex with focal adhesion kinase (FAK, also known as PTK2) and Src, and that this signalling pathway lies downstream of fascin-microtubule association in the control of adhesion stability. These findings shed light on new non actin-dependent roles for fascin and might have implications for the design of therapies to target fascin in metastatic disease. PMID- 26542023 TI - Ras-activated Dsor1 promotes Wnt signaling in Drosophila development. AB - Wnt/Wingless (Wg) and Ras-MAPK signaling both play fundamental roles in growth and cell fate determination, and when dysregulated, can lead to tumorigenesis. Several conflicting modes of interaction between Ras-MAPK and Wnt signaling have been identified in specific cellular contexts, causing synergistic or antagonistic effects on target genes. We find novel evidence that the Drosophila homolog of the dual specificity kinases MEK1/2 (also known as MAP2K1/2), Downstream of Raf1 (Dsor1), is required for Wnt signaling. Knockdown of Dsor1 results in loss of Wg target gene expression, as well as reductions in stabilized Armadillo (Arm; Drosophila beta-catenin). We identify a close physical interaction between Dsor1 and Arm, and find that catalytically inactive Dsor1 causes a reduction in active Arm. These results suggest that Dsor1 normally counteracts the Axin-mediated destruction of Arm. We find that Ras-Dsor1 activity is independent of upstream activation by EGFR, and instead it appears to be activated by the insulin-like growth factor receptor to promote Wg signaling. Taken together, our results suggest that there is a new crosstalk pathway between insulin and Wg signaling that is mediated by Dsor1. PMID- 26542022 TI - CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and response to injury in the zebrafish heart. AB - Cyclin dependent kinase (Cdk)9 acts through the positive transcription elongation factor-b (P-TEFb) complex to activate and expand transcription through RNA polymerase II. It has also been shown to regulate cardiomyocyte hypertrophy, with recent evidence linking it to cardiomyocyte proliferation. We hypothesised that modification of CDK9 activity could both impair and enhance the cardiac response to injury by modifying cardiomyocyte proliferation. Cdk9 expression and activity were inhibited in the zebrafish (Danio rerio) embryo. We show that dephosphorylation of residue Ser2 on the C-terminal domain of RNA polymerase II is associated with impaired cardiac structure and function, and cardiomyocyte proliferation and also results in impaired functional recovery following cardiac laser injury. In contrast, de-repression of Cdk9 activity, through knockdown of La-related protein (Larp7) increases phosphorylation of Ser2 in RNA polymerase II and increases cardiomyocyte proliferation. Larp7 knockdown rescued the structural and functional phenotype associated with knockdown of Cdk9. The balance of Cdk9 and Larp7 plays a key role in cardiomyocyte proliferation and response to injury. Larp7 represents a potentially novel therapeutic target to promote cardiomyocyte proliferation and recovery from injury. PMID- 26542024 TI - Spatial and temporal translational control of germ cell mRNAs mediated by the eIF4E isoform IFE-1. AB - Regulated mRNA translation is vital for germ cells to produce new proteins in the spatial and temporal patterns that drive gamete development. Translational control involves the de-repression of stored mRNAs and their recruitment by eukaryotic initiation factors (eIFs) to ribosomes. C. elegans expresses five eIF4Es (IFE-1-IFE-5); several have been shown to selectively recruit unique pools of mRNA. Individual IFE knockouts yield unique phenotypes due to inefficient translation of certain mRNAs. Here, we identified mRNAs preferentially translated through the germline-specific eIF4E isoform IFE-1. Differential polysome microarray analysis identified 77 mRNAs recruited by IFE-1. Among the IFE-1 dependent mRNAs are several required for late germ cell differentiation and maturation. Polysome association of gld-1, vab-1, vpr-1, rab-7 and rnp-3 mRNAs relies on IFE-1. Live animal imaging showed IFE-1-dependent selectivity in spatial and temporal translation of germline mRNAs. Altered MAPK activation in oocytes suggests dual roles for IFE-1, both promoting and suppressing oocyte maturation at different stages. This single eIF4E isoform exerts positive, selective translational control during germ cell differentiation. PMID- 26542026 TI - One-pot synthesis of carbazoles via tandem C-C cross-coupling and reductive amination. AB - We have developed a highly efficient synthetic route to carbazoles that employs sequential C-C/C-N bond formation via Suzuki cross-coupling and Cadogan cyclization using commercially available or easily preparable starting materials. The developed method is compatible with electron neutral, rich or deficient substrates. The synthetic utility of this method was demonstrated by the concise syntheses of four natural products (glycozoline, glycozolicine, glycozolidine and clausenalene). PMID- 26542025 TI - Feasibility and clinical impact of sharing patient-reported symptom toxicities and performance status with clinical investigators during a phase 2 cancer treatment trial. AB - BACKGROUND: Clinicians can miss up to half of patients' symptomatic toxicities in cancer clinical trials and routine practice. Although patient-reported outcome questionnaires have been developed to capture this information, it is unclear whether clinicians will make use of patient-reported outcomes to inform their own toxicity documentation, or to prompt symptom management activities. METHODS: 44 lung cancer patients that participated in a phase 2 treatment trial self-reported 13 symptomatic toxicities derived from the National Cancer Institute's Common Terminology Criteria for Adverse Events and Karnofsky Performance Status via tablet computers in waiting areas immediately preceding scheduled visits. During visits, clinicians viewed patients' self-reported toxicity and performance status ratings on a computer interface and could agree or disagree/reassign grades ("shared" reporting). Agreement of clinicians with patient-reported grades was tabulated, and compared using weighted kappa statistics. Clinical actions in response to patient-reported severe (grade 3/4) toxicities were measured (e.g. treatment discontinuation, dose reduction, supportive medications). For comparison, 45 non-trial patients with lung cancer being treated in the same clinic by the same physicians were simultaneously enrolled in a parallel cohort study in which patients also self-reported toxicity grades but reports were not shared with clinicians ("non-shared" reporting). RESULTS: Toxicities and performance status were reported by patients and reviewed by clinicians at (780/782) 99.7% of study visits in the phase 2 trial which used "shared" reporting. Clinicians agreed with patients 93% of the time with kappas 0.82-0.92. Clinical actions were taken in response to 67% of severe patient-reported toxicities. In the "non-shared" reporting comparison group, clinicians agreed with patients 56% of the time with kappas 0.04-0.48 (significantly worse than shared reporting for all symptoms), and clinical actions were taken in response to 44% of severe patient-reported toxicities. CONCLUSION: Clinicians will frequently agree with patient-reported symptoms and performance status, and will use this information to guide documentation and symptom management. (ClinicalTrials.gov: NCT00807573). PMID- 26542027 TI - Intra-vesical Prostatic Protrusion (IPP) Can Be Reduced by Prostatic Artery Embolization. AB - BACKGROUND: Prostate artery embolization (PAE) is a new approach to improve lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia. PAE results in global reduction of prostate volume (PV). There are no data available on the efficacy of PAE in reducing intra-vesical prostatic protrusion (IPP), an anatomic feature that is clinically related with bladder outlet obstruction and LUTS. OBJECTIVE: To assess the results of PAE in patients with significant IPP due to median lobe hyperplasia and to compare the IPSS decrease and IPP change. MATERIAL AND METHODS: Prospective analysis of 18 consecutive patients with significant IPP (>5 mm) related to median lobe hyperplasia undergoing PAE using 30-500-MUm-calibrated trisacryl microspheres. We measured IPP on sagittal T2 weighted images before and 3 months after PAE. IPSS and clinical results were also evaluated at 3 months. RESULTS: PAE resulted in significant IPP reduction (1.57 cm +/- 0.55 before PAE and 1.30 cm +/- 0.46 after PAE, p = 0.0005) (Fig. 1) with no complication. IPSS, quality of life (QoL), total prostate-specific antigen (PSA) level, and PV showed significant reduction after PAE, and maximum urinary flow rate (Q max) showed significant increase after PAE. No significant change of International Index of Erectile Function (IIEF) for clinical evaluation after PAE. A significant correlation was found between the IPP change and the IPSS change (r = 0.636, p = 0.0045). CONCLUSION: Patients had significant IPP reduction as well as significant symptomatic improvement after PAE, and these improvements were positively correlated. PMID- 26542028 TI - Percutaneous Treatment of Intrahepatic Biliary Leak: A Modified Occlusion Balloon Technique. AB - PURPOSE: To report a novel modified occlusion balloon technique to treat biliary leaks. METHODS: A 22-year-old female patient underwent liver transplantation with biliary-enteric anastomosis. She developed thrombosis of the common hepatic artery and extensive ischemia in the left hepatic lobe. Resection of segments II and III was performed and a biliary-cutaneous leak originating at the resection plane was identified in the early postoperative period. Initial treatment with percutaneous transhepatic drainage was unsuccessful. Therefore, an angioplasty balloon was coaxially inserted within the biliary drain and positioned close to the leak. RESULTS: The fistula output abruptly decreased after the procedure and stopped on the 7th day. At the 3-week follow-up, cholangiography revealed complete resolution of the leakage. CONCLUSION: This novel modified occlusion balloon technique was effective and safe. However, greater experience and more cases are necessary to validate the technique. PMID- 26542029 TI - How to train glioma cells to die: molecular challenges in cell death. AB - The five-year survival rate for patients with malignant glioma is less than 10%. Despite aggressive chemo/radiotherapy these tumors have remained resistant to almost every interventional strategy evaluated in patients. Resistance to these agents is attributed to extrinsic mechanisms such as the tumor microenvironment, poor drug penetration, and tumoral heterogeneity. In addition, genetic and molecular examination of these tumors has revealed defective apoptotic regulation, enhanced pro-survival autophagy signaling, and a propensity for necrosis that aids in the adaptation to environmental stress and resistance to treatment. The combination of extrinsic and intrinsic hallmarks in glioma contributes to the multifaceted resistance to traditional anti-tumor agents. Here we describe the biology of the disease relevant to therapeutic resistance, with a specific focus on molecular deregulation of cell death pathways. Emerging studies investigating the targeting of these pathways including BH3 mimetics and autophagy inhibitors that are being evaluated in both the preclinical and clinical settings are discussed. This review highlights the pathways exploited by glioblastoma cells that drive their hallmark pro-survival predisposition and makes therapy development such a challenge. PMID- 26542030 TI - Outcome of treatment of recurrent glioblastoma multiforme in elderly and/or frail patients. AB - Optimal treatment of recurrent glioblastoma multiforme (rGBM) in elderly and/or frail patients remains virtually unexplored, the best supportive care (BSC) only is routinely administered due to the fatal prognosis. We evaluated the impact of different treatment methods on post-progression survival (PPS) and overall survival (OS) of such patients. Data from 98 elderly and/or frail rGBM patients, treated initially with 1-week or 3-week radiotherapy (RT) within the phase III IAEA study (2010-2013), were analyzed. KPS at relapse and salvage treatment methods were recorded. Kaplan-Meier method was used to estimate PPS and OS for different treatment modalities. Eighty-four patients experienced recurrence: 47 (56%) received BSC, 21 (25%)-chemotherapy (CHT), 8 (9.5%)-surgery, 3 (3.5%)-RT, for 5 (6%) the data was unavailable. Median OS from randomization for all 84 patients was 35 weeks: 55 versus 30 weeks for any treatment versus BSC, p < 0.0001. Median PPS was 15 weeks: 23 weeks with any treatment versus 9 weeks with BSC, p < 0.0001. For local treatment (surgery and/or RT) median PPS was 51 versus 21 weeks for CHT, p = 0.36. In patients with poor KPS (<=60) at relapse median PPS was 9 weeks with BSC versus 21 weeks with any treatment, p = 0.014. In poor KPS patients median PPS for local treatment was 14 weeks versus 21 weeks with CHT, p = 0.88. An active therapeutic approach may be beneficial for selected elderly and/or frail rGBM patients. Poor KPS patients may also benefit from active treatment, but there is no benefit of local treatment over CHT. PMID- 26542031 TI - Natural killer cell hyporesponsiveness and impaired development in a CD247 deficient patient. PMID- 26542032 TI - Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. PMID- 26542034 TI - Allergic disease is associated with childhood seizures: An analysis of the 1997 2013 National Health Interview Survey. PMID- 26542033 TI - Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency. AB - BACKGROUND: Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. OBJECTIVES: Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. METHODS: Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. RESULTS: The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid related orphan receptor (ROR) gammat, IFN-gamma, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORgammat and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN gamma(+)RORgammat(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. CONCLUSIONS: An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. PMID- 26542035 TI - The Bacillus anthracis Exosporium: What's the Big "Hairy" Deal? AB - In some Bacillus species, including Bacillus subtilis, the coat is the outermost layer of the spore. In others, such as the Bacillus cereus family, there is an additional layer that envelops the coat, called the exosporium. In the case of Bacillus anthracis, a series of fine hair-like projections, also referred to as a "hairy" nap, extends from the exosporium basal layer. The exact role of the exosporium in B. anthracis, or for any of the Bacillus species possessing this structure, remains unclear. However, it has been assumed that the exosporium would play some role in infection for B. anthracis, because it is the outermost structure of the spore and would make initial contact with host and immune cells during infection. Therefore, the exosporium has been a topic of great interest, and over the past decade much progress has been made to understand its composition, biosynthesis, and potential roles. Several key aspects of this spore structure, however, are still debated and remain undetermined. Although insights have been gained on the interaction of exosporium with the host during infection, the exact role and significance of this complex structure remain to be determined. Furthermore, because the exosporium is a highly antigenic structure, future strategies for the next-generation anthrax vaccine should pursue its inclusion as a component to provide protection against the spore itself during the initial stages of anthrax. PMID- 26542037 TI - Infectious Risks of Air Travel. AB - Infectious diseases are still among the leading causes of death worldwide due to their persistence, emergence, and reemergence. As the recent Ebola virus disease and MERS-CoV outbreaks demonstrate, the modern epidemics and large-scale infectious outbreaks emerge and spread quickly. Air transportation is a major vehicle for the rapid spread and dissemination of communicable diseases, and there have been a number of reported outbreaks of serious airborne diseases aboard commercial flights including tuberculosis, severe acute respiratory syndrome, influenza, smallpox, and measles, to name a few. In 2014 alone, over 3.3 billion passengers (a number equivalent to 42% of the world population) and 50 million metric tons of cargo traveled by air from 41,000 airports and 50,000 routes worldwide, and significant growth is anticipated, with passenger numbers expected to reach 5.9 billion by 2030. Given the increasing numbers of travelers, the risk of infectious disease transmission during air travel is a significant concern, and this chapter focuses on the current knowledge about transmission of infectious diseases in the context of both transmissions within the aircraft passenger cabin and commercial aircraft serving as vehicles of worldwide infection spread. PMID- 26542039 TI - Diseases Transmitted by Cats. AB - Humans and cats have shared a close relationship since ancient times. Millions of cats are kept as household pets, and 34% of households have cats. There are numerous diseases that may be transmitted from cats to humans. General modes of transmission, with some overlapping features, can occur through inhalation (e.g., bordetellosis); vector-borne spread (e.g., ehrlichiosis); fecal-oral route (e.g., campylobacteriosis); bite, scratch, or puncture (e.g., rabies); soil-borne spread (e.g., histoplasmosis); and direct contact (e.g., scabies). It is also likely that the domestic cat can potentially act as a reservoir for many other zoonoses that are not yet recognized. The microbiology of cat bite wound infections in humans is often polymicrobial with a broad mixture of aerobic (e.g., Pasteurella, Streptococcus, Staphylococcus) and anaerobic (e.g., Fusobacterium, Porphyromonas, Bacteroides) microorganisms. Bacteria recovered from infected cat bite wounds are most often reflective of the oral flora of the cat, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. PMID- 26542040 TI - Integrated Pathophysiology of Pyelonephritis. AB - Pyelonephritis represents a subset of urinary tract infections that occur from bacteria ascending from the lower to the upper reaches of the genitourinary system, such as the kidney. The renal system contains a range of hydrodynamically and immunologically challenging, interconnected microenvironments where the invading pathogen may populate during the course of the infection. The situation at the infection foci changes dynamically, vacillating between bacterial colonization and clearance, to which the outcome is a summation of all host pathogen elements in play. A selection of important determinants includes factors of microbial origin, effects of eukaryotic cell signaling, physiological facets of the infected organ, and signals from distal organs. Improved understanding of the multifactorial aspects of molecular pathogenesis of infection requires intravital, cross-disciplinary approaches with high spatio-temporal resolution. The advancement of such approaches promises to eventually provide a comprehensive understanding of the integrated pathophysiology of pyelonephritis. PMID- 26542041 TI - Reservoirs of Extraintestinal Pathogenic Escherichia coli. AB - Several potential reservoirs for the Escherichia coli strains that cause most human extraintestinal infections (extraintestinal pathogenic E. coli; ExPEC) have been identified, including the human intestinal tract and various non-human reservoirs, such as companion animals, food animals, retail meat products, sewage, and other environmental sources. Understanding ExPEC reservoirs, chains of transmission, transmission dynamics, and epidemiologic associations will assist greatly in finding ways to reduce the ExPEC-associated disease burden. The need to clarify the ecological behavior of ExPEC is all the more urgent because environmental reservoirs may contribute to acquisition of antimicrobial resistance determinants and selection for and amplification of resistant ExPEC. In this chapter, we review the evidence for different ExPEC reservoirs, with particular attention to food and food animals, and discuss the public health implications of these reservoirs for ExPEC dissemination and transmission. PMID- 26542036 TI - Proteus mirabilis and Urinary Tract Infections. AB - Proteus mirabilis is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls'-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers P. mirabilis with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. P. mirabilis uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering P. mirabilis pathogenesis. PMID- 26542042 TI - Urosepsis: Overview of the Diagnostic and Treatment Challenges. AB - Urosepsis is defined as sepsis caused by an infection in the urogenital tract. In approximately 30% of all septic patients the infectious focus is localized in the urogenital tract, mainly due to obstructions at various levels, such as ureteral stones. Urosepsis may also occur after operations in the urogenital tract. In urosepsis, complete bacteria and components of the bacterial cell wall from the urogenital tract trigger the host inflammatory event and act as exogenous pyrogens on eukaryotic target cells of patients. A burst of second messenger molecules leads to several different stages of the septic process, from hyperactivity to immunosuppression. As pyelonephritis is the most frequent cause for urosepsis, the kidney function is therefore most important in terms of cause and as a target organ for dysfunction in the course of the sepsis.Since effective antimicrobial therapy must be initiated early during sepsis, the empiric intravenous therapy should be initiated immediately after microbiological sampling. For the selection of appropriate antimicrobials, it is important to know risk factors for resistant organisms and whether the sepsis is primary or secondary and community or nosocomially acquired. In addition, the preceding antimicrobial therapies should be recorded as precisely as possible. Resistance surveillance should, in any case, be performed locally to adjust for the best suitable empiric treatment. Treatment challenges arise from the rapid increase of antibiotic resistance in Gram-negative bacteria, especially extended-spectrum beta-lactamase (ESBL)-producing bacteria. Treatment of urosepsis comprises four basic strategies I) supportive therapy (stabilizing and maintaining blood pressure), II) antimicrobial therapy, III) control or elimination of the complicating factor, and IV) specific sepsis therapy. PMID- 26542043 TI - Origin and Dissemination of Antimicrobial Resistance among Uropathogenic Escherichia coli. AB - Antimicrobial agents of various types have important bearing on the outcomes of microbial infections. These agents may be bacteriostatic or -cidal, exert their impact via various means, originate from a living organism or a laboratory, and appropriately be used in or on living tissue or not. Though the primary focus of this chapter is on resistance to the antimicrobial agents used to treat uropathogenic Escherichia coli (UPEC)-caused urinary tract infections (UTIs), some attention will be given to UPEC's resistance to silver-containing antiseptics, which may be incorporated into catheters to prevent foreign body associated UTIs. PMID- 26542044 TI - Infections Acquired in the Garden. AB - Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis. PMID- 26542045 TI - Sexually Transmitted Diseases and Travel: From Boudoir to Bordello. AB - Travel has historically been an important risk factor for acquisition of sexually transmitted infections (STIs). Travel is often associated with a sense of adventure, periods of loneliness, and exploration away from one's home environment-which often form a milieu in which sexual activity can occur with new partners. Survey data clearly demonstrate that out-of-country travel is associated with recruitment of new sex partners and increased STI risk. Pretravel counseling to prevent STI risk is variable, and there is little evidence that it modifies risk behavior. Some travel occurs specifically for sexual purposes, such as the sexual tourism junkets to Southeast Asian destinations which became popular during the 1980s or the more recent rise in the popularity of circuit parties for men who have sex with men. Some travel situations pose particularly high risks. For example, military deployments and assignments to work camps such as those for oil extraction occur in the context of large groups of individuals of reproductive age, often predominantly males, exposed to high levels of stress in unfamiliar environments. Additionally, over the past decade, the Internet has dramatically changed the ability to identify sexual partners while traveling. PMID- 26542046 TI - Asymptomatic Bacteriuria and Bacterial Interference. AB - Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from <1% in newborns to 10% to 20% of women age 80 years, but is uncommon in men until after age 50 years. Individuals with underlying genitourinary abnormalities, including indwelling devices, may also have a high frequency of asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term-care facilities, from 25% to 50% of women and 15% to 40% of men. Escherichia coli is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients. PMID- 26542047 TI - Infections Associated with Exotic Cuisine: The Dangers of Delicacies. AB - "Exotic" food dishes are an expression of regional culture, religion, and ethnicity worldwide. With the increase in international travel to remote areas of the world, globalization of the food supply, and changes in food habits, more people are consuming dishes once considered exotic. Such behavioral changes require awareness by consumers and clinicians about the risks of food-borne infections. This chapter addresses pathogens associated with consumption of raw or undercooked seafood including anisakidosis, Diphyllobothrium latum infection, flukes, and other infectious and toxin-mediated diseases. We discuss the geographic distribution of the pathogens, symptomatology, and basic principles of treatment. Food products derived from turtles, snakes, and other reptiles are reviewed, and we address the risk of gnathostomiasis, sparganosis, trichinellosis, and other pathogens. In discussing infections associated with undercooked beef, pork, and bush meat, we address dysentery, amebiasis, toxoplasmosis, Taenia infections, and risks of novel viral infections, among others. We also review infectious risks from poultry, dairy, and other food items, focusing on those organisms encountered less frequently by clinicians in developed countries. The wide range of infectious organisms related to exotic cuisine underscores the importance of educating the adventurous traveler and warrants continued vigilance on the part of the clinician. PMID- 26542038 TI - Structure, Function, and Assembly of Adhesive Organelles by Uropathogenic Bacteria. AB - Bacteria assemble a wide range of adhesive proteins, termed adhesins, to mediate binding to receptors and colonization of surfaces. For pathogenic bacteria, adhesins are critical for early stages of infection, allowing the bacteria to initiate contact with host cells, colonize different tissues, and establish a foothold within the host. The adhesins expressed by a pathogen are also critical for bacterial-bacterial interactions and the formation of bacterial communities, including biofilms. The ability to adhere to host tissues is particularly important for bacteria that colonize sites such as the urinary tract, where the flow of urine functions to maintain sterility by washing away non-adherent pathogens. Adhesins vary from monomeric proteins that are directly anchored to the bacterial surface to polymeric, hair-like fibers that extend out from the cell surface. These latter fibers are termed pili or fimbriae, and were among the first identified virulence factors of uropathogenic Escherichia coli. Studies since then have identified a range of both pilus and non-pilus adhesins that contribute to bacterial colonization of the urinary tract, and have revealed molecular details of the structures, assembly pathways, and functions of these adhesive organelles. In this review, we describe the different types of adhesins expressed by both Gram-negative and Gram-positive uropathogens, what is known about their structures, how they are assembled on the bacterial surface, and the functions of specific adhesins in the pathogenesis of urinary tract infections. PMID- 26542049 TI - Sports: The Infectious Hazards. AB - Although the medical complications of sports are usually traumatic in nature, infectious hazards also arise. While blood-borne pathogens such as HIV, hepatitis B, and hepatitis C, cause significant illness, the risk of acquiring these agents during sporting activities is minimal. Skin infections are more commonplace, arising from a variety of microbial agents including bacterial, fungal, and viral pathogens. Sports involving water contact can lead to enteric infections, eye infections, or disseminated infections such as leptospirosis. Mumps, measles, and influenza are vaccine-preventable diseases that have been transmitted during sporting events, both in players and in spectators. Prevention is the key to many of these infections. Players should be vaccinated and should not participate in sports if their infection can be spread by contact, airborne, or droplet transmission. PMID- 26542051 TI - Improved Transversal Relaxivity for Highly Crystalline Nanoparticles of Pure gamma-Fe2O3 Phase. AB - Pure and highly crystalline gamma-Fe2O3 nanocrystals (NCs) are obtained when hydrolysis and oxidation of a Fe(II) organometallic precursor are performed in successive steps. Their synthesis in pure alkylamine leads to NCs of about 6 nm. In aqueous solutions of poly(vinyl)pyrrolidone, such pristine NCs form aggregates of about 150 nm that exhibit a high transversal relaxivity (r2 =466 mM(-1) s(-1)) about four times higher than that of a commercial Feridex magnetic resonance imaging (MRI) contrast agent. Consequently, they provide a significant decrease in the NMR signal at very short echo time (8 ms), which is of paramount importance in clinical practice because of the reduced duration of MRI measurements. PMID- 26542048 TI - Post-Genomic Analysis of Members of the Family Vibrionaceae. AB - Similar to other genera and species of bacteria, whole genomic sequencing has revolutionized how we think about and address questions of basic Vibrio biology. In this review we examined 36 completely sequenced and annotated members of the Vibrionaceae family, encompassing 12 different species of the genera Vibrio, Aliivibrio, and Photobacterium. We reconstructed the phylogenetic relationships among representatives of this group of bacteria by using three housekeeping genes and 16S rRNA sequences. With an evolutionary framework in place, we describe the occurrence and distribution of primary and alternative sigma factors, global regulators present in all bacteria. Among Vibrio we show that the number and function of many of these sigma factors differs from species to species. We also describe the role of the Vibrio-specific regulator ToxRS in fitness and survival. Examination of the biochemical capabilities was and still is the foundation of classifying and identifying new Vibrio species. Using comparative genomics, we examine the distribution of carbon utilization patterns among Vibrio species as a possible marker for understanding bacteria-host interactions. Finally, we discuss the significant role that horizontal gene transfer, specifically, the distribution and structure of integrons, has played in Vibrio evolution. PMID- 26542052 TI - 40 yrs CPMAS & 25 yrs REDOR. PMID- 26542050 TI - Obesity Impairs the Action of the Neuroendocrine Ghrelin System. AB - Ghrelin is a metabolic hormone that promotes energy conservation by regulating appetite and energy expenditure. Although some studies suggest that antagonizing ghrelin function attenuates body weight gain and glucose intolerance on a high calorie diet, there is little information about the metabolic actions of ghrelin in the obese state. In this review, we discuss the novel concept of obesity induced central ghrelin resistance in neural circuits regulating behavior, and impaired ghrelin secretion from the stomach. Interestingly, weight loss restores ghrelin secretion and function, and we hypothesize that ghrelin resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity. PMID- 26542053 TI - [History of conservative spinal therapy]. AB - Hippocrates was the first to intensively describe and document the principles for the treatment of injuries and diseases of the spine. His principles for abrupt treatment of the "hunchback" were followed by physicians even up to the end of the nineteenth century. The non-operative treatment of scoliosis was improved in the beginning of the sixteenth century by the introduction of mechanical devices that started the development of corsets which are still in use in modern scoliosis treatment. Stretching beds were only in temporary use. With the beginning of the nineteenth century gymnastics and physiotherapy became more and more important. Manual therapy was exercised by physicians until the late Middle Ages. After a long period of time in which bonesetters and other laymen performed manual therapy it was professionalized at the end of the nineteenth century again by the introduction of osteopathy and chiropractic. In Germany the development and introduction of manual treatment started relatively late in the twentieth century, predominantly as manual medicine. PMID- 26542054 TI - Effect of 22 Novel Cytochrome P450 2D6 (CYP2D6) Variants Found in the Chinese Population on Hemangeol Metabolism In Vitro. AB - BACKGROUND AND OBJECTIVES: Hemangeol, approved for the treatment of proliferative infantile hemangiomas requiring systemic therapy, is metabolized by cytochrome P450 2D6 (CYP2D6), which is a highly polymorphic enzyme that metabolizes a large number of drugs. More than 100 CYP2D6 allelic variants have been reported so far, including 22 novel variants that discovered in our lab in the Chinese population. Our study aimed to probe the enzymatic activity of these variants toward hemangeol in vitro with recombinant microsomes that expressed in sf21 insect cells using a baculovirus-mediated expression system. METHODS: The wild-type CYP2D6.1 and other variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) were incubated with 1-200 MUM hemangeol for 50 min at 37 degrees C. Then the products were extracted, and signal detection was performed by high-performance liquid chromatography with fluorescence detector. RESULTS: All of the variants exhibited changed apparent Michaelis-Menten constant (Km) or maximum velocity of the reaction (V max) values compared with that of wild-type protein. The intrinsic clearances (V max /Km) were significantly decreased by 0.37 to 42.74 %. However, CYP2D6.92 and CYP2D6.96 showed no or minimal enzymatic activity as no concentration of 4'-hydroxypropranolol was detected. CONCLUSIONS: The comprehensive in vitro assessment of CYP2D6 variants provides significant insights into allele-specific activity towards hemangeol in vivo. PMID- 26542055 TI - Comparison of the predictive ability of albuminuria and dipstick proteinuria for mortality in the Japanese population: the Yamagata (Takahata) study. AB - BACKGROUND: Albuminuria and proteinuria are known risk factors for premature death. This study compared the ability of albuminuria and proteinuria to predict mortality in a community-based population. METHODS: We evaluated the urinary albumin creatinine ratio (ACR) and proteinuria by dipstick at a baseline survey and examined the association between the 7-year mortality and three categories (albuminuria [ACR >= 30 mg/g], trace proteinuria, and >=[1+] proteinuria) in 3446 Japanese subjects at a local health check. RESULTS: Albuminuria, >=trace proteinuria, and >=(1+) proteinuria were identified in 514 (14.9 %), 290 (8.4 %), and 151 (4.4 %) subjects, respectively. There were 138 deaths during the follow up period, including 41 cardiovascular deaths. A Kaplan-Meier analysis showed that all-cause mortality significantly increased along with the increase in ACR and proteinuria levels (log-rank P < 0.01). The mortality rate (deaths per 1000 person-year) was higher in subjects with albuminuria (12.8), >=trace proteinuria (12.6), and >=(1+) proteinuria (16.2) than in all subjects (6.9). A Cox proportional hazard model analysis showed that all three categories were significant predictors of all-cause mortality in the unadjusted model, although after adjustment for possible confounders, a significant association was observed only with albuminuria. Albuminuria, but not proteinuria, was a significant predictor of cardiovascular mortality in both the unadjusted and adjusted models. CONCLUSION: Albuminuria had a high prevalence and was strongly associated with mortality, as compared with proteinuria by dipstick, suggesting that albuminuria might be a superior predictor of poor prognosis in the Japanese population. PMID- 26542056 TI - Resident Memory T Cells as Surrogate Markers of the Efficacy of Cancer Vaccines. AB - Cancer vaccine boost via the cervicovaginal rather than the intramuscular route of immunization appears to be crucial to induce genital CD8(+) T cells and tumor regression. This clinical activity is correlated with the ability of the mucosal boost to elicit resident memory T cells in the genital tract. PMID- 26542057 TI - DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer. AB - PURPOSE: Prospective-retrospective assessment of the TOP1 gene copy number and TOP1 mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan. TOP1 copy number status was analyzed by fluorescence in situ hybridization (FISH) using a TOP1/CEN20 dual-probe combination. TOP1 mRNA data were available from previous analyses. RESULTS: TOP1 FISH and follow-up data were obtained from 534 patients. TOP1 gain was identified in 27% using a single probe enumeration strategy (>=4 TOP1 signals per cell) and in 31% when defined by a TOP1/CEN20 ratio >= 1.5. The effect of additional irinotecan was not dependent on TOP1 FISH status.TOP1 mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized by TOP1 mRNA expression >= third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment by TOP1 mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasing TOP1 mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to the TOP1 copy number, a trend was demonstrated for a predictive property of TOP1 mRNA expression. On the basis of TOP1 mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer. PMID- 26542058 TI - ERRalpha Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer. AB - PURPOSE: Estrogen-related receptor alpha (ERRalpha) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERRalpha in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients. EXPERIMENTAL DESIGN: Cox proportional hazards regression was used to evaluate the significance of associations between ERRalpha gene expression levels and patient DMFS in a previously published microarray dataset representing 2,000 breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976-1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERRalpha. The phenotypic effects associated with ERRalpha modulation were studied using immunoblotting analyses and wound-healing assay. RESULTS: We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERRalpha expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERRalpha gene and protein expression. Reduced ERRalpha expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies. CONCLUSIONS: Taken together, these data show that ERRalpha expression predicts response to tamoxifen treatment, and ERRalpha could be a biomarker of tamoxifen sensitivity and a prognostic factor in TNBC. PMID- 26542060 TI - The clinical benefits, ethics, and economics of stratified medicine and companion diagnostics. AB - The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified medicines in autoimmune, cardiovascular, neurodegenerative, respiratory, and other conditions. Of 53 oncology targets with a launched therapeutic, 44 have competing therapeutics. Only 12 of 141 Phase III candidates addressing new targets face no competition. CDx choices might alter competitive positions and reimbursement. Under current diagnostic incentives, payers see novel stratified medicines that improve public health and increase costs, but do not observe companion diagnostics for legacy treatments that would reduce costs. It would be in the interests of payers to rediscover their heritage of direct investment in diagnostic development. PMID- 26542059 TI - Protecting Newborns Against Pertussis: Treatment and Prevention Strategies. AB - Pertussis is a potentially severe respiratory disease, which affects all age groups from young infants to older adults and is responsible for an estimated 195,000 deaths occurred globally in 2008. Active research is ongoing to better understand the pathogenesis, immunology, and diagnosis of pertussis. For diagnosis, molecular assays (e.g., polymerase chain reaction) for detection of Bordetella pertussis have become more widely available and support improved outbreak detection. In children, pertussis vaccines have been incorporated into routine immunization schedules and deployed for pertussis outbreak control. Lower levels of vaccine coverage are now being observed in communities where vaccine hesitancy is rising. Additionally, recognition that newborn babies are at risk of pertussis in the USA and UK has led to recommendations to immunize pregnant women. Among adolescents and older adults in the USA, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular pertussis (Tdap) Vaccines are recommended, but substantial individual- and system-level barriers exist that will make achieving national Healthy People 2020 targets for immunization challenging. Current antimicrobial regimens for pertussis are focused on reducing the severity of disease, reducing rates of sequelae, and minimizing transmission of infection to susceptible individuals. Continued surveillance for pertussis will be important to identify opportunities for reducing young infants' exposure and reducing the impact of outbreaks among school-aged children. Laboratory-based surveillance for newly emerging strains of B. pertussis will be important to identify strains that may evade protection elicited by currently available vaccines. Efforts to develop new-generation pertussis vaccines should be considered now in anticipation of vaccine development programs, which may require ten or more years to deliver a licensed vaccine. PMID- 26542062 TI - Managing Cognitive Load to Uncover an Unusual Cause of Syncope: Exercises in Clinical Reasoning. PMID- 26542061 TI - Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma. AB - Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high-risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Endoscopic biopsies from 188 high-risk subjects were histologically classified according to the current WHO classification for BD using a numeric histology score ranging from 1 to 8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic, and immunohistochemical variables. Subjects with a higher frequency of sites that persist or progress to high-grade dysplasia (>=37.5% persist/progress, N = 35 versus <37.5% persist/progress, N = 114) show a significant association with development of incident invasive SCC (adjusted HR, 7.84; 95% confidence interval, 1.56-39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 U higher than in subjects without lung cancer. Current smoking, elevated Ki67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow-up histology scores. These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD. PMID- 26542063 TI - Capsule Commentary on Fortuna et al., Health Conditions and Functional Status in Adults with Autism: A Cross Sectional Evaluation. PMID- 26542064 TI - Detection of human papillomavirus in laryngeal squamous cell carcinoma: Systematic review and meta-analysis. AB - BACKGROUND: Recent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies. OBJECTIVE: To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC. METHODS: Literature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [CI]), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size. Potential publication bias was estimated using funnel plot symmetry. RESULTS: One hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non-polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both. CONCLUSIONS: Variability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression. LEVEL OF EVIDENCE: NA. PMID- 26542065 TI - Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies. AB - The aim of this meta-analysis was to clarify whether a longer interval between the end of neoadjuvant chemoradiotherapy (nCRT) and surgery is associated with better outcomes in esophageal cancer. nCRT followed by surgery is the most common approach for patients with resectable esophageal cancer. Operations are performed within 2-8 weeks after nCRT; however, the optimal interval between nCRT and surgery for esophageal cancer is unknown. We performed a systematic literature search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Clinical Trials database for studies published between January 2000 and December 2014. Eligible studies were prospective or retrospective studies of esophageal cancer that assessed the effects of intervals longer or shorter than 7 8 weeks between the end of nCRT and surgery. The primary end-points were the overall survival (OS) and pathologic complete response (pCR). Secondary end points were anastomotic leak, R0 resection, and postoperative mortality rate. A meta-analysis was performed to estimate odds ratios (ORs) using fixed-effect and random-effect models, with Review Manager 5.2. The five studies that met the eligibility requirements included 1,016 patients: 520 in the shorter interval group (<=7-8 weeks) and 496 in the longer interval group (>7-8 weeks). The results of our meta-analysis indicate that a longer interval between nCRT and surgery may be disadvantageous for 2-year OS (OR = 1.40, 95% confidence interval [CI]: 1.09-1.80, P = 0.010) and R0 resection rate (OR = 1.71, 95% CI: 1.14-2.22, P = 0.009). The pCR, anastomotic leak rate, and postoperative morbidity were similar in the two groups. A longer interval (more than the standard 7-8 weeks) from the end of preoperative nCRT to surgery did not increase the rate of pCR in esophageal cancer, and the different intervals had similar effects on anastomotic leak rate and postoperative mortality rates. However, the longer interval between nCRT and surgery may be disadvantageous for long-term OS. These results should be validated prospectively in a randomized trial. PMID- 26542066 TI - Investigation of activating and inhibitory killer cell immunoglobulin-like receptors and their putative ligands in type 1 diabetes (T1D). AB - Genetic and environmental factors play important roles in predisposing an individual to the development of type 1 diabetes (T1D). Several studies have investigated the role of killer cell immunoglobulin-like receptors (KIRs) and their HLA-class I ligands in susceptibility to T1D development, but only some of these studies have demonstrated an association. KIRs and their corresponding HLA class I ligands were investigated in Saudi patients with T1D compared with healthy controls. No significant differences in KIR gene distribution were observed between T1D patients and healthy controls. However, the homozygous C1/C1 ligand was considered a risk factor in predisposing individuals to T1D, whereas C2/C2 and HLA-Bw4 were considered protective factors against T1D. KIR2DL2/2DS2 C1C1 and KIR2DL3-C1C1 were significantly associated with T1D, and KIR2DS1-C2C2 and KIR2DL1-C2C2 were significantly less frequent in T1D patients. Stratification of KIR-HLA class I ligands in terms of the absence/presence of specific genotypes has different indications for susceptibility to T1D. PMID- 26542067 TI - Significant association of the KIR2DL3/HLA-C1 genotype with susceptibility to Crohn's disease. AB - We aimed to analyze the possible association of KIR/HLA-C genotypes with the susceptibility to Crohn's disease (CD) in a Spanish population. A total of 125 patients with CD and 339 healthy controls were selected for this study. KIR and HLA-C typing were developed by sequence-specific oligonucleotide probing. We found that the centromeric A/A genotype and HLA-C1 combination was significantly increased in CD patients (P<10(-3)). The KIR2DL3/2DL3 genotype was significantly increased in CD patients (P<0.0005). Moreover, we also observed a highly significant increase of KIR2DL3-HLA-C1 homozygosis in CD patients (P<0.0005). Our results confirm the relevance of the KIR2DL2/KIR2DL3 genes and their interaction with HLA-C to CD. We show that the contribution of the KIR genes to CD susceptibility extends beyond the association with individual KIRs, with an imbalance between activating and inhibitory KIR genes seeming to influence the susceptibility to CD. PMID- 26542068 TI - Daclatasvir-containing all-oral regimens for the treatment of hepatitis C virus infection. AB - The treatment of chronic hepatitis C is revolutionizing rapidly. The aim of this study is to review the efficacy and safety of daclatasvir (DCV)-containing all oral regimens in clinical studies for chronic hepatitis C treatment. Using PubMed and search terms of 'DCV,' 'hepatitis C virus (HCV) treatment,' and 'HCV NS5A inhibitors,' literature on the clinical development of DCV, as well as abstracts presented at the April 2015 annual meeting of the European Association for the Study of the Liver (EASL) and November 2014 annual meeting of the American Association for the Study of Liver Diseases were reviewed. The final search was undertaken on 14 July 2015. With its potent antiviral activity to all HCV genotypes (GT) demonstrated in preclinical, phases 1-3 studies, DCV has been acting as a very competent team player in clinical trials of all-oral regimens. It is generally safe and well tolerated with a low genetic barrier to resistance and low potential for drug-drug interaction. Administered with a non-structural protein 3 (NS3) protease inhibitor (asunaprevir, ASV) with or without a non nucleoside NS5B polymerase inhibitor (beclabuvir, BCV), or a nucleotide NS5B polymerase inhibitor (sofosbuvir, SOF), DCV is able to achieve greater than a 90 % HCV eradication rate in both treatment-naive and treatment-experienced patients with GT 1. A triple combination regimen with DCV/ASV/BCV results in 100% sustained virologic response (SVR) rates in HCV GT 4 treatment-naive subjects. DCV/SOF combination also had demonstrated up to 90-% SVR rates in GT 3-infected non-cirrhotic patients. The efficacy and safety of DCV-containing all-oral regimens highlight a new era of interferon-free therapy for chronic hepatitis C. PMID- 26542069 TI - Genetic causal beliefs about obesity, self-efficacy for weight control, and obesity-related behaviours in a middle-aged female cohort. AB - OBJECTIVE: Obesity is a heritable condition with well-established risk-reducing behaviours. Studies have shown that beliefs about the causes of obesity are associated with diet and exercise behaviour. Identifying mechanisms linking causal beliefs and behaviours is important for obesity prevention and control. DESIGN: Cross-sectional multi-level regression analyses of self-efficacy for weight control as a possible mediator of obesity attributions (diet, physical activity, genetic) and preventive behaviours in 487 non-Hispanic White women from South King County, Washington. MAIN OUTCOME MEASURES: Self-reported daily fruit and vegetable intake and weekly leisure-time physical activity. RESULTS: Diet causal beliefs were positively associated with fruit and vegetable intake, with self-efficacy for weight control partially accounting for this association. Self efficacy for weight control also indirectly linked physical activity attributions and physical activity behaviour. Relationships between genetic causal beliefs, self-efficacy for weight control, and obesity-related behaviours differed by obesity status. Self-efficacy for weight control contributed to negative associations between genetic causal attributions and obesity-related behaviours in non-obese, but not obese, women. CONCLUSION: Self-efficacy is an important construct to include in studies of genetic causal beliefs and behavioural self regulation. Theoretical and longitudinal work is needed to clarify the causal nature of these relationships and other mediating and moderating factors. PMID- 26542070 TI - Can cemented dual-mobility cups be used without a reinforcement device in cases of mild acetabular bone stock alteration in total hip arthroplasty? AB - INTRODUCTION: Cemented versions of dual-mobility cups (DMCs), helpful in cases of bone stock alteration, are usually used in association with a reinforcement device. To simplify the intervention in elderly subjects or those with a poor bone stock, the cups can be cemented directly into the bone, but the long-term result remains uncertain. We conducted a retrospective study in this population so as to: (1) assess whether cemented fixation of a DMC without a reinforcement device leads to a higher loosening rate, (2) confirm its efficacy in preventing dislocations in subjects at high risk of instability, and (3) measure the functional results. HYPOTHESIS: Cemented fixation of a DMC is reliable in cases of moderate alteration of bone stock. MATERIAL AND METHODS: Sixty-four patients (66 hips) undergoing implantation of a cemented DMC (SaturneTM) without a reinforcement device were included in this single-center retrospective study. Their mean age was 79.8 years (range, 40-95 years). The indications varied: hip osteoarthritis (30.3%), prosthesis revision (44.0%), and trauma (25.8%). The patients were evaluated radiologically and clinically at follow-up. The main evaluation criterion was the revision rate for aseptic loosening. Dislocations, the infection rate, and the Postel Merle d'Aubigne (PMA) score were noted. RESULTS: At the mean follow-up of 4.2 years, three (4.6%) patients had been lost to follow-up and 22 (33.3%) had died. There was one case of aseptic loosening (1.5%). Cup survival was 98% at 5 years (95%CI [94-100]). There were no dislocations. There was one revision for infection. The mean PMA score was 15.5 (range, 9-18). DISCUSSION: The frequency of acetabular loosening was comparable to the frequency in cemented DMCs with a reinforcement device. A cemented DMC without a reinforcement device is possible and is a simple and viable option when there is moderate bone stock alteration. LEVEL OF EVIDENCE: IV, retrospective cohort study. PMID- 26542072 TI - Fear of Unemployment and its Effect on the Mental Health of Spouses. AB - Unemployment has been shown to have adverse effects on different aspects of a person's life, and even the fear of losing a job affects individuals negatively. In addition, not only the individuals directly affected but also their spouses and other family members might be affected. Using data from the German Socio economic Panel, this study analyzes the relationship between individual job worries and spouse's mental well-being. The empirical results remain robust to different specifications and indicate that fear of job loss is negatively related to spouses' mental well-being and that this relationship seems to be stronger in single-income than in dual-income households. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542071 TI - Pachychoroid neovasculopathy and age-related macular degeneration. AB - Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 * 10(-5)) and showed a greater subfoveal choroidal thickness (p = 3.4 * 10(-14)). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 * 10(-3)). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies. PMID- 26542073 TI - A minimalistic microbial food web in an excavated deep subsurface clay rock. AB - Clay rocks are being considered for radioactive waste disposal, but relatively little is known about the impact of microbes on the long-term safety of geological repositories. Thus, a more complete understanding of microbial community structure and function in these environments would provide further detail for the evaluation of the safety of geological disposal of radioactive waste in clay rocks. It would also provide a unique glimpse into a poorly studied deep subsurface microbial ecosystem. Previous studies concluded that microorganisms were present in pristine Opalinus Clay, but inactive. In this work, we describe the microbial community and assess the metabolic activities taking place within borehole water. Metagenomic sequencing and genome-binning of a porewater sample containing suspended clay particles revealed a remarkably simple heterotrophic microbial community, fueled by sedimentary organic carbon, mainly composed of two organisms: a Pseudomonas sp. fermenting bacterium growing on organic macromolecules and releasing organic acids and H2, and a sulfate reducing Peptococcaceae able to oxidize organic molecules to CO(2). In Opalinus Clay, this microbial system likely thrives where pore space allows it. In a repository, this may occur where the clay rock has been locally damaged by excavation or in engineered backfills. PMID- 26542074 TI - Temporal dynamics of the metabolically active rumen bacteria colonizing fresh perennial ryegrass. AB - This study investigated successional colonization of fresh perennial ryegrass (PRG) by the rumen microbiota over time. Fresh PRG was incubated in sacco in the rumens of three Holstein * Friesian cows over a period of 8 h, with samples recovered at various times. The diversity of attached bacteria was assessed using 454 pyrosequencing of 16S rRNA (cDNA). Results showed that plant epiphytic communities either decreased to low relative abundances or disappeared following rumen incubation, and that temporal colonization of the PRG by the rumen bacteria was biphasic with primary (1 and 2 h) and secondary (4-8 h) events evident with the transition period being with 2-4 h. A decrease in sequence reads pertaining to Succinivibrio spp. and increases in Pseudobutyrivibrio, Roseburia and Ruminococcus spp. (the latter all order Clostridiales) were evident during secondary colonization. Irrespective of temporal changes, the continually high abundances of Butyrivibrio, Fibrobacter, Olsenella and Prevotella suggest that they play a major role in the degradation of the plant. It is clear that a temporal understanding of the functional roles of these microbiota within the rumen is now required to unravel the role of these bacteria in the ruminal degradation of fresh PRG. PMID- 26542076 TI - Evaluation of the bacterial microbiome of two flea species using different DNA isolation techniques provides insights into flea host ecology. AB - Fleas (Siphonaptera) are ubiquitous blood-sucking pests of animals worldwide and are vectors of zoonotic bacteria such as Rickettsia and Bartonella. We performed Ion Torrent PGM amplicon sequencing for the bacterial 16S rRNA gene to compare the microbiome of the ubiquitous cat flea (Ctenocephalides f. felis) and the host specific echidna stickfast flea (Echidnophaga a. ambulans) and evaluated potential bias produced during common genomic DNA-isolation methods. We demonstrated significant differences in the bacterial community diversity between the two flea species but not between protocols combining surface sterilisation with whole flea homogenisation or exoskeleton retention. Both flea species were dominated by obligate intracellular endosymbiont Wolbachia, and the echidna stickfast fleas possessed the endosymbiont Cardinium. Cat fleas that were not surface sterilised showed presence of Candidatus 'Rickettsia senegalensis' DNA, the first report of its presence in Australia. In the case of Rickettsia, we show that sequencing depth of 50 000 was required for comparable sensitivity with Rickettsia qPCR. Low-abundance bacterial genera are suggested to reflect host ecology. The deep-sequencing approach demonstrates feasibility of pathogen detection with simultaneous quantitative analysis and evaluation of the inter relationship of microbes within vectors. PMID- 26542075 TI - What is living on your dog's skin? Characterization of the canine cutaneous mycobiota and fungal dysbiosis in canine allergic dermatitis. AB - To characterize the skin-associated fungal microbiota (mycobiota) in dogs, and to evaluate the influence of body site, individual dog or health status on the distribution of fungi, next-generation sequencing was performed targeting the internal transcribed spacer region. A total of 10 dogs with no history of skin disease were sampled at 10 distinct body sites consisting of haired and mucosal skin, and 8 dogs with diagnosed skin allergies were sampled at six body sites commonly affected by allergic disease. Analysis of similarities revealed that body site was not an influencing factor on membership or structure of fungal communities in healthy skin; however, the mucosal sites were significantly reduced in fungal richness. The mycobiota from body sites in healthy dogs tended to be similar within a dog, which was visualized in principle coordinates analysis (PCoA) by clustering of all sites from one dog separate from other dogs. The mycobiota of allergic skin was significantly less rich than that of healthy skin, and all sites sampled clustered by health status in PCoA. Interestingly, the most abundant fungi present on canine skin, across all body sites and health statuses, were Alternaria and Cladosporium--two of the most common fungal allergens in human environmental allergies. PMID- 26542077 TI - An infant with MLH3 variants, FOXG1-duplication and multiple, benign cranial and spinal tumors: A clinical exome sequencing study. AB - A 4-month-old male infant presented with severe developmental delay, cerebellar, brainstem, and cutaneous hemangiomas, bilateral tumors (vestibular, hypoglossal, cervical, and lumbar spinal), and few cafe-au-lait macules. Cerebellar and lumbar tumor biopsies revealed venous telangiectasia and intraneural perineuroma, respectively. Sequencing NF1, NF2, and RASA1 (blood), and NF2 and SMARCB1 (lumbar biopsy) was negative for pathogenic mutations. Clinical exome sequencing (CES), requested for tumor syndrome diagnosis, revealed two heterozygous missense variants, c.359T>C;p.Phe120Ser and c.3344G>A;p.Arg1115Gln, in MLH3 (NM_001040108.1), a DNA mismatch repair (MMR) gene, Polyphen-predicted as probably damaging, and benign, respectively. Sanger sequencing confirmed both variants in the proband, and their absence in the mother; biological father unavailable. Both biopsied tissues were negative for microsatellite instability, and expressed MLH1, MSH2, PMS2, MSH6, and MLH3 immunohistochemically. Chromosomal microarray showed a 133 kb segment copy number duplication of 14q12 region encompassing FOXG1, possibly explaining the developmental delay, but not the tumors. The presence of MLH3 variants with multiple benign neural and vascular tumors was intriguing for their possible role in the pathogenesis of these neoplasms, which were suspicious for, but not diagnostic of, constitutional MMR deficiency. However, functional assays of non-neoplastic patient-derived cells showed intact base-base MMR function. Also, no previous FOXG1-aberrant patient was reported with tumors. We now report a 3-year-old FOXG1-duplicated patient with a yet undescribed tumor syndrome with clinical features of neurofibromatosis types I and II, where several validation studies could not ascertain the significance of CES findings; further studies may elucidate precise mechanisms and diagnosis for clinical management, including tumor surveillance. PMID- 26542078 TI - Exercise-related transient abdominal pain secondary to median arcuate ligament syndrome: a case report. AB - Exercise-related transient abdominal pain is a common entity in young athletes. An uncommon aetiology of this type of pain is median arcuate ligament syndrome. This article details an 18-year-old field hockey player who presented with a 1 year history of exercise-related transient abdominal pain. Despite a trial of preventative strategies, the patient's pain persisted, prompting surgical intervention. Following a laparoscopic median arcuate ligament release, the patient's symptoms resolved. Therefore, when exercise-related transient abdominal pain persists despite precautionary measures, median arcuate ligament syndrome should be considered. PMID- 26542079 TI - Toward a cure for HIV--Seeking effective therapeutic vaccine strategies. AB - This review article focuses on the rationale and evaluation of therapeutic vaccines against HIV. This strategy has been developed in order to restore or restimulate HIV-specific immunity in patients treated with antiretroviral therapies. Despite the lack of good candidate vaccines against HIV, two objectives have been targeted during the past 15 years. Therapeutic immunization was first proposed to help control virus relapses during treatment interruptions. More recently, the concept of therapeutic immunization has been boosted by efforts to reach HIV remission or cure, in combination to HIV reactivating agents, to help purge HIV reservoirs in a "shock and kill" strategy. This review analyses the rationales for these strategies and the results of the most widely therapeutic vaccines designed to generate T-cell immunity, i.e. recombinant viral vectors and dendritic cell-based strategies, while extremely few strategies targeted HIV-specific Abs. Only marginal control of HIV was obtained with cellular-based strategies, suggesting that approaches targeting or using broadly neutralizing Abs, should be of benefit for future efforts of therapeutic immunization against HIV in the quest toward a cure for HIV. PMID- 26542080 TI - The human rs1050286 polymorphism alters LOX-1 expression through modifying miR-24 binding. AB - The up-regulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX 1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX-1 overexpression is crucial. Predictive analysis showed a putative hsa-miR-24 binding site in the 3'UTR of OLR1, 'naturally' mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR-24 targets OLR1 3'UTR-G, but not 3'UTR-A (P < 0.0005). The functional relevance of miR-24 in regulating the expression of OLR1 was established by overexpressing miR-24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down-regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR-24 binding affinity to the 3'UTR of OLR1, causing a more efficient post transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk. PMID- 26542081 TI - Proximal segmentation of the dorsal mesogastrium reveals new anatomical implications for laparoscopic surgery. AB - Generally, the gold standard of radical surgery for gastrointestinal (GI) tumors is en bloc resection of primary lesions and their related tissues. For gastric cancer, the ideal surgical treatment should be D2 radical gastrectomy plus complete mesogastrium excision. Complete mesogastrium excision is rarely done or mentioned since little is known about the mesogastrium and its presence is still with controversy. Topographically, the "mesogastrium" refers to a peri-gastric structure composed of "fascia propria", enveloping lymph nodes, blood vessels and adipose tissues, which by connecting to the stomach, suspends from the posterior abdominal wall. In this study, by employing video laparoscopy, a number of proximal segments of dorsal mesogastrium were found being extensively scattered around the pancreas. The structure of the mesogastrium was further identified intraoperatively and then confirmed both grossly and histologically after the operation. Our results demonstrated the existence of mesogastrium (gastric mesentery) and its architecture. We suggest for the first time a "Table model" to describe the relationship between the stomach and gastric mesenteries enveloped by fascia propria, which might provide an improvement in the surgical methods for excision of gastric cancer. PMID- 26542083 TI - Satyrization and satyrization-resistance in competitive displacements of invasive mosquito species. AB - Competitive displacements or reductions of resident populations of insects, often effected by a related species, may be caused by a variety of mechanisms. Satyrization is a form of mating interference in which males of one species mate with females of another species, significantly decreasing their fitness and not generating hybrids. Satyrization has been established to be the probable cause of competitive displacements of resident mosquitoes by invasive species, especially of Aedes aegypti by Aedes albopictus, two important vectors of dengue and chikungunya viruses. Mathematical models predict that even low levels of asymmetric mating interference are capable of producing competitive displacements or reductions. Couplings of virgin Ae. aegypti females with Ae. albopictus males effectively sterilize these females through the monogamizing actions of male accessory gland products, but the converse interspecific mating does not impact the future reproduction of Ae. albopictus females. Populations of Ae. aegypti exposed to satyrization quickly evolve resistance to interspecific mating, which is believed to ameliorate reproductive interference from, and promote co existence with, Ae. albopictus. The evolution of satyrization resistance among Ae. aegypti in laboratory cages is accompanied by fitness costs, such as reduced fecundity and slower receptivity to conspecific males. Cage experiments and field observations indicate that Ae. albopictus males are capable of satyrizing females of other species of the Stegomyia subgenus, potentially leading to competitive displacements, and possible extinctions, especially of endemic species on islands. Examination of other examples of reproductive interference in insects reveals few parallels to the mechanism and outcomes of satyrization by Ae. albopictus. We conclude by posing the hypothesis that satyrization may favor the ecological success of Ae. albopictus, and suggest many lines for future research on this phenomenon. PMID- 26542082 TI - Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. AB - BACKGROUND AND OBJECTIVE: Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke. Here, we evaluated the ability of VNS paired with rehabilitative training to improve recovery of forelimb strength when initiated many weeks after a cortical and subcortical ischemic lesion in subjects with stable, chronic motor deficits. METHODS: Rats were trained to perform an automated, quantitative measure of voluntary forelimb strength. Once proficient, rats received injections of endothelin-1 to cause a unilateral cortical and subcortical ischemic lesion. Then, 6 weeks after the lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered 2 hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9). RESULTS: VNS paired with rehabilitative training significantly improved recovery of forelimb function compared with control groups. The Paired VNS group displayed an 86% recovery of strength, the Rehab group exhibited 47% recovery, and the Delayed VNS group exhibited 42% recovery. Improvement in forelimb function was sustained in the Paired VNS group after the cessation of stimulation, potentially indicating lasting benefits. No differences in intensity of rehabilitative training, lesion size, or MAP-2 expression were observed between groups. CONCLUSION: VNS paired with rehabilitative training confers significantly greater recovery of forelimb function after chronic ischemic stroke in rats. PMID- 26542084 TI - Quantification, 2DE analysis and identification of enriched glycosylated proteins from mouse muscles: Difficulties and alternatives. AB - One of the problems with 2DE is that proteins present in low amounts in a sample are usually not detected, since their signals are masked by the predominant proteins. The elimination of these abundant proteins is not a guaranteed solution to achieve the desired results. The main objective of this study was the comparison of common and simple methodologies employed for 2DE analysis followed by MS identification, focusing on a pre-purified sample using a wheat germ agglutinin (WGA) column. Adult male C57Black/Crj6 (C57BL/6) mice were chosen as the model animal in this study; the gastrocnemius muscles were collected and processed for the experiments. The initial fractionation with succinylated WGA was successful for the elimination of the most abundant proteins. Two quantification methods were employed for the purified samples, and bicinchoninic acid (BCA) was proven to be most reliable for the quantification of glycoproteins. The gel staining method, however, was found to be decisive for the detection of specific proteins, since their structures affect the interaction of the dye with the peptide backbone. The Coomassie Blue R-250 dye very weakly stained the gel with the WGA purified sample. When the same gel was stained with silver nitrate, however, MS could positively assign 12 new spots. The structure of the referred proteins was not found to be prone to interaction with Coomassie blue. PMID- 26542085 TI - Government Response to the Discovery of a Rabies Virus Reservoir Species on a Previously Designated Rabies-Free Island, Taiwan, 1999-2014. AB - Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores. PMID- 26542088 TI - Application of a fluorescent biosensor based-on magneto-gamma-Fe2 O3 -methyldopa nanoparticles for adsorption of human serum albumin. AB - Understanding and controlling the interaction between the polymer methyldopa (2 amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid) (PMDP)-gamma-Fe2 O3 nanoparticles and biological fluids is important if the potential of nanoparticles (NPs) in biomedicine is to be realized. Physicochemical studies on the interactions between proteins and NPs are influenced by the surface properties of the NPs. To identify the effects of the NP surface, interactions between human serum albumin (HSA) and PMDP-gamma-Fe2 O3 NPs were investigated. Here, the adsorption of HSA onto small (10-30 nm diameter) PMDP-gamma-Fe2 O3 NPs was quantitatively analyzed using spectroscopic methods. The fluorescence quenching data were checked for the inner-filter effect, the main confounding factor in the observed quenching. The binding constants, Ka , were calculated at different temperatures, using a nonlinear fit to the experimental data, and the thermodynamic parameters ?H, ?S and ?G were given. The obtained thermodynamic signature suggests that hydrophobic interactions at least are present. This result indicates that the structure of the protein turns from a structureless denatured state at pH 3 into an ordered biologically active native state on addition of PMDP-gamma-Fe2 O3 NPs. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542087 TI - Histopathologic patterns among achalasia subtypes. AB - BACKGROUND: Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns. METHODS: We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by two expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes. KEY RESULTS: Manometry studies were categorized as follows: type I (n = 20), type II (n = 20), type III (n = 3), and esophagogastric junction outflow obstruction (EGJOO) (n = 3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs 13/20, p = 0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p = 0.016). CD3(+) /CD8(+) cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO). CONCLUSIONS & INFERENCES: The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings - from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology - emphasizes that 'achalasia' represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction. PMID- 26542089 TI - Epigenetic-Imprinting Changes Caused by Neonatal Fasting Stress Protect From Future Fasting Stress. AB - Unfavourable nutritional conditions during the neonatal critical period can cause both acute metabolic disorders and severe metabolic syndromes in later life. These phenomena have been tightly related to the epigenetic modification controlling the balance between satiety and hunger in the hypothalamus. In the present study, we investigated epigenetic modification associated with both the fasting stress effects and the short-term resilience to fasting stress in the hypothalamic paraventricular nucleus (PVN) of chicks. Fasting for 24 h at 3 days of age (D) (i.e. D3) significantly increased global methylation at lysine 27 of histone 3 (H3K27) and its specific histone methyltransferase (HMT) expression level in the PVN. Because global methylation could not fully reveal the changes at specific genes, the regulation of the gene for brain-derived neurotrophic factor (Bdnf), which was recently also found to have an anorexigenic effect, was evaluated as a potential target. Chromatin immunoprecipitation assay analysis revealed that tri- (me3) and di-methylated (me2) H3K27 exhibited an instant (on D4 only) and latent increase (on both D11 and D41), respectively, at the putative promoter of Bdnf after 24 h of fasting on D3. This indicated that fasting could regulate energy-expenditure-related genes via modifying methylation at H3K27, which we suspected might be a protective mechanism for keeping the inner environment homeostatic. To test this hypothesis, a short-term repetitive fasting stress was applied to chickens, which were fasted for 24 h either on D10 only or on both D3 and D10. It was found that pre-existing fasting on D3 could induce a short-term fasting resilience, which rescued the reduction of Bdnf expression from future fasting on D10. We call this phenomenon the 'molecular memory', which was mainly conducted by HMTs and H3K27me2/me3 in the PVN. In conclusion, chicks respond to fasting with dynamic methylation at H3K27 in the PVN during the neonatal critical period. This allows the PVN to form a 'molecular memory', which keeps the individual inner environment homeostatic and resilient to future fasting over the short term. PMID- 26542090 TI - The outcome of management of "troublesome" vs "non-troublesome" phalangeal neck fractures in children less than 2 years of age. AB - BACKGROUND: Several authors have indicated that there are specific poor prognostic factors which may affect the outcome of management of phalangeal neck fractures. In the authors' centre, phalangeal neck fractures with any of these poor prognostic factors are labelled "troublesome". Any of the following five criteria will qualify the fracture to be regarded as "troublesome": concurrent vascular compromise of the fractured digit, open/partial amputation injuries, comminution of the fractured phalangeal head, concurrent epiphyseal or juxta epiphyseal fractures distal to the fractured phalangeal head, and all Type III fractures (as per Al-Qattan classification). METHODS: The effect of these poor prognostic factors has not been investigated in the youngest paediatric age group; the hands of whom are known to be most forgiving. The purpose of this study is to compare the outcome of management of seven "troublesome" vs nine "non troublesome" phalangeal neck fractures in children less than 2 years of age. Demographic data (age, sex, fracture site/type, and troublesome factors) were reviewed for the 16 cases. All patients were treated according to a specific protocol, and the outcome was documented using a modified Al-Qattan's outcome grading system. RESULTS: Of the nine children with non-troublesome fractures, eight obtained a satisfactory outcome and the ninth case had an unsatisfactory outcome. In contrast, all seven children with troublesome fractures had an unsatisfactory outcome and the difference was highly significant (p = 0.0007). CONCLUSION: The authors strongly advise discussing the outcome of troublesome fractures with the parents and also advise documenting this in the file (prior to management) for medico-legal reasons. PMID- 26542091 TI - Bayesian evidence synthesis to estimate HIV prevalence in men who have sex with men in Poland at the end of 2009. AB - HIV spread in men who have sex with men (MSM) is an increasing problem in Poland. Despite the existence of a surveillance system, there is no direct evidence to allow estimation of HIV prevalence and the proportion undiagnosed in MSM. We extracted data on HIV and the MSM population in Poland, including case-based surveillance data, diagnostic testing prevalence data and behavioural data relating to self-reported prior diagnosis, stratified by age (?35, >35 years) and region (Mazowieckie including the capital city of Warsaw; other regions). They were integrated into one model based on a Bayesian evidence synthesis approach. The posterior distributions for HIV prevalence and the undiagnosed fraction were estimated by Markov Chain Monte Carlo methods. To improve the model fit we repeated the analysis, introducing bias parameters to account for potential lack of representativeness in data. By placing additional constraints on bias parameters we obtained precisely identified estimates. This family of models indicates a high undiagnosed fraction [68.3%, 95% credibility interval (CrI) 53.9 76.1] and overall low prevalence (2.3%, 95% CrI 1.4-4.1) of HIV in MSM. Additional data are necessary in order to produce more robust epidemiological estimates. More effort is urgently needed to ensure timely diagnosis of HIV in Poland. PMID- 26542092 TI - Flow cytometry in hematological nonmalignant disorders. AB - Multiparameter flow cytometry (MFC) has become an integral part of the diagnosis and classification of hematological malignancies. However, several nonmalignant or premalignant disorders may benefit from this technology in hematology laboratories. This review provides information on the normal immunophenotypic characteristics of peripheral blood leukocyte subsets and their modifications in several clinical conditions. The usefulness of MFC and the specific markers that can be investigated in hyperlymphocytosis, infection, hypereosinophilia, paroxysmal nocturnal hemoglobinuria, and large granular lymphocyte disorders is described. Mention is also made of the developments of MFC for analyses of red blood cells or platelets. PMID- 26542093 TI - Microfluidic co-cultures with hydrogel-based ligand trap to study paracrine signals giving rise to cancer drug resistance. AB - Targeted cancer therapies are designed to deactivate signaling pathways used by cancer cells for survival. However, cancer cells are often able to adapt by activating alternative survival pathways, thereby acquiring drug resistance. An emerging theory is that autocrine or paracrine growth factor signaling in the cancer microenvironment represent an important mechanism of drug resistance. In the present study we wanted to examine whether paracrine interactions between groups of melanoma cells result in resistance to vemurafenib - an FDA approved drug targeting the BRAF mutation in metastatic melanoma. We used a vemurafenib resistant melanoma model which secretes fibroblast growth factor (FGF)-2 to test our hypothesis that this is a key paracrine mediator of resistance to vemurafenib. Sensitive cells treated with media conditioned by resistant cells did not protect from the effects of vemurafenib. To query paracrine interactions further we fabricated a microfluidic co-culture device with two parallel compartments, separated by a 100 MUm wide hydrogel barrier. The gel barrier prevented resorting/contact of cells while permitting paracrine cross-talk. In this microfluidic system, sensitive cells did become refractive to the effects of vemurafenib when cultured adjacent to resistant cells. Importantly, incorporation of FGF-2 capture probes into the gel barrier separating the two cell types prevented onset of resistance to vemurafenib. Microfluidic tools described here allow for more sensitive analysis of paracrine signals, may help better understand signaling in the cancer microenvironment and may enable development of more effective cancer therapies. PMID- 26542094 TI - Performance of South African children on the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS DP). AB - BACKGROUND: Substantial development in social communication skills occurs in the first two years of life. Growth should be evident in sharing emotion and eye gaze; rate of communication, communicating for a variety of functions; using gestures, sounds and words; understanding language, and using functional and pretend actions with objects in play. A delay in these early social communication skills may be the first sign of a developmental delay in young children in nearly all categories of disabilities-including specific language impairment, autism spectrum disorder, HIV/AIDS, lack of environmental stimulation or institutionalization, and global developmental delays-and early detection of these delays is critical for enrolment in appropriate early intervention services. AIMS: No standardized tests of early social communication skills exist for very young children in South Africa (SA). An existing evaluation tool that has the potential to be culturally fair for children from cultural backgrounds different to the standardization group is the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS DP). This study aimed to document the performance of a group of English-speaking SA children ranging in age from 12 to 24 months on the CSBS DP and to compare this performance with the original standardization sample. METHODS & PROCEDURES: Sixty-seven English-speaking SA children from a range of cultural and linguistic backgrounds were assessed on the CSBS DP Behaviour Sample. Group scores were compared with the original standardization sample using inferential statistics. OUTCOMES & RESULTS: The results provide preliminary support for the suitability and validity of the face to-face Behaviour Sample as a measure of early social communication skills in this sample of English-speaking SA children from a range of cultural groups between 12 and 24 months of age. CONCLUSIONS & IMPLICATIONS: While further research in the SA population is needed, these findings are a first step towards validating a culturally appropriate measure for early detection of social communication delays in a sample of SA toddlers. PMID- 26542095 TI - American College of Cardiology: Environmental Scanning Report Update 2015. PMID- 26542097 TI - Clinical efficacy of early loading versus conventional loading of dental implants. AB - The aim of this study was to determine the clinical differences between early and conventional loading protocols for dental implants. A comprehensive search of the Medline, Embase, and OVID databases for studies published through January 10, 2015 was conducted. Fourteen studies were included in our analysis. We found that early loading imposed a significantly higher risk of implant failure than did conventional loading (risk ratio = 2.09, 95% confidence interval [CI] [1.18, 3.69], P = 0.01), while no significant differences between the methods were found with regards to the marginal bone loss (weighted mean differences [WMD] = 0.11, 95% CI [-0.07, 0.28], P = 0.23), periotest value (WMD = 0.02, 95% CI [-0.83, 0.87], P = 0.96), or implant stability quotient (WMD = 0.79, 95% CI [-0.03, 1.62], P = 0.06). As for the health status of the peri-implant tissue, conventionally loaded implants demonstrated better performance than did early loaded implants. Subgroup analyses demonstrated that the sample size, time of publication, loading definition, implant position, extent, and restoration type influenced the results. Although early implant loading is convenient and comfortable for patients, this method still cannot achieve the same clinical outcomes as the conventional loading method. PMID- 26542098 TI - (Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level. AB - Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4'-trans tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi targeting drug for treating G-R patients. PMID- 26542099 TI - Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens. AB - Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3-year-old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia. PMID- 26542100 TI - Imaging mass spectrometry in drug discovery and development. PMID- 26542096 TI - Meta-analysis identifies seven susceptibility loci involved in the atopic march. AB - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 * 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 * 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema. PMID- 26542101 TI - Is Right Ventricular Remodeling in Pulmonary Hypertension Dependent on Etiology? An Echocardiographic Study. AB - AIMS: Survival in patients (pts) with pulmonary hypertension (PH) differs between subgroups at similar levels of pressure overload. We set to analyze right ventricular (RV) morphology and function in different types of PH using conventional and deformation imaging echocardiography. MATERIAL AND METHODS: Thirty-four pts with PH: 12 pts with idiopathic pulmonary arterial hypertension (IPAH, 42.2 +/- 13 years), 11 pts with chronic thromboembolic PH (CTEPH, 50.8 +/- 12 years), 11 pts with Eisenmenger syndrome [ES 41.2 +/- 15 years, 4 with atrial septal defect (ASD) and 7 with ventricular septal defect (VSD)], and 13 age matched healthy individuals (38.1 +/- 15 years) were evaluated. The following echocardiographic parameters were measured: echo-derived systolic pulmonary pressure (sPAPecho), RV end-diastolic diameter (RVEDD), RV wall thickness (RVWT), TAPSE, RV fractional area change (RVFAC), Tei index, peak systolic velocity of the tricuspid ring (S't), and speckle tracking-derived RV free wall strain. Furthermore, right heart catheterization (RHC) was performed in pts with PH and mean, and systolic pulmonary artery pressure (mPAPcath, sPAPcath), cardiac output (CO), cardiac index (COi), and pulmonary vascular resistance (PVR) were noted. RESULTS: The levels of mPAPcath and sPAPcath were similar between pts with PH (pANOVA = NS). Patients with ES had higher COi compared to other groups (2.94 +/- 0.79, 2.28 +/- 0.69, and 1.74 +/- 0.46 L/min/m(2) for pts with ES, IPAH, and CTEPH respectively, pANOVA = 0.004, P post hoc ES versus all other groups < 0.05). TAPSE, Tei index, and S't were similar between groups and impaired versus controls (pANOVA < 0.001, P post hoc between groups of patients = NS). Patients with ES had better RVFAC (41.1 +/- 9, 30.5 +/- 10.8, 23.2 +/- 9.8%) and RV free wall strain (-20.6 +/- 3.5, -16.3 +/- 7.5, -10.8 +/- 5%), as well as an increased thickness of the RV free wall compared to other groups of patients (9.2 +/- 1.5, 7.2 +/- 1 and 7.2 +/- 1.6 mm for pts with ES, IPAH and CTEPH, respectively) (pANOVA<0.001, P post hoc <0.05 ES versus all other groups). RVFAC and RV free wall strain significantly correlated with COi (r = 0.53, P = 0.006 and r = -0.77, P < 0.001, respectively). CONCLUSION: Patients with ES have a more hypertrophied RV free wall, better RV performance as assessed by RVFAC and RV free wall strain and increased COi compared to other types of PH. Furthermore, RV performance appears to be less dependent on the level of pressure overload. These findings could contribute to the better survival profile of patients with ES. PMID- 26542102 TI - A meta-analysis provides evidence that prenatal smoking exposure decreases age at menarche. AB - Since studies of association between prenatal tobacco exposure and age at menarche have reported inconsistent results so far, we conducted a meta-analysis to examine this association. In total 36 relevant articles (1995-2014) were identified, 17 of which satisfied the inclusion criteria and were used in the analysis. Nearly one month decrease (-0.092 [95%CI:-0.160, -0.024] year) in age at menarche was found in women who were exposed to tobacco in utero. The meta regression analysis showed that average year of birth in the cohorts might significantly influence association between maternal smoking and daughter's age at menarche. Based on results obtained from 5 studies where age at menarche was treated as a categorical variable, maternal smoking status during pregnancy increased a risk for daughters to have menarche earlier than at 11 years old by 15%. PMID- 26542103 TI - Prevalence and characteristics of intended adolescent pregnancy: an analysis of the Canadian maternity experiences survey. AB - BACKGROUND: There is limited research focusing on adolescent women who intended to become pregnant, as majority of research examines unintended adolescent pregnancies. The objective was to examine the prevalence and characteristics of Canadian adolescent women who intended to become pregnant. METHODS: The analysis was based on the national 2006 Maternity Experiences Survey consisting of women who had a singleton live birth. The sample was restricted to adolescent women between 15 to 19 years of age. The main outcome of this study was the adolescent woman's pregnancy intention. A variety of sociodemographic, maternal, and pregnancy related factors were examined using a multivariable logistic regression. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were reported for all variables. RESULTS: The sample size was 290, weighted to represent 2224 adolescent women. Based on the adjusted model, the odds of experiencing an intended pregnancy were increased if the adolescent woman was between 18-19 years old (OR 2.62, 95 % CI 1.05, 6.57), had a partner (OR 2.37, 95 % CI 1.12, 4.99), experienced no violence/abuse (OR 3.08, 95 % CI 1.38, 6.86), and consumed no alcohol before pregnancy (OR 3.17, 95 % CI 1.56, 6.45). Additionally, adolescent women who reported drug use prior to pregnancy were more likely to have an intended pregnancy (OR 0.39, 95 % CI 0.16, 0.95). CONCLUSION: The findings from this study can be used as the basis for future research to investigate the characteristics and needs represented by this group of adolescents and to aid in the development of effective policies and programs. PMID- 26542104 TI - Functional rehabilitation of upper limb apraxia in poststroke patients: study protocol for a randomized controlled trial. AB - BACKGROUND: Upper limb apraxia is a common disorder associated with stroke that can reduce patients' independence levels in activities of daily living and increase levels of disability. Traditional rehabilitation programs designed to promote the recovery of upper limb function have mainly focused on restorative or compensatory approaches. However, no previous studies have been completed that evaluate a combined intervention method approach, where patients concurrently receive cognitive training and learn compensatory strategies for enhancing daily living activities. METHODS/DESIGN: This study will use a two-arm, assessor blinded, parallel, randomized controlled trial design, involving 40 patients who present a left- or right-sided unilateral vascular lesion poststroke and a clinical diagnosis of upper limb apraxia. Participants will be randomized to either a combined functional rehabilitation or a traditional health education group. The experimental group will receive an 8-week combined functional program at home, including physical and occupational therapy focused on restorative and compensatory techniques for upper limb apraxia, 3 days per week in 30-min intervention periods. The control group will receive a conventional health education program once a month over 8 weeks, based on improving awareness of physical and functional limitations and facilitating the adaptation of patients to the home. Study outcomes will be assessed immediately postintervention and at the 2-month follow-up. The primary outcome measure will be basic activities of daily living skills as assessed with the Barthel Index. Secondary outcome measures will include the following: 1) the Lawton and Brody Instrumental Activities of Daily Living Scale, 2) the Observation and Scoring of ADL Activities, 3) the De Renzi Test for Ideational Apraxia, 4) the De Renzi Test for Ideomotor Apraxia, 5) Recognition of Gestures, 6) the Test of Upper Limb Apraxia (TULIA), and 7) the Quality of Life Scale For Stroke (ECVI-38). DISCUSSION: This trial is expected to clarify the effectiveness of a combined functional rehabilitation approach compared to a conservative intervention for improving upper limb movement and function in poststroke patients. TRIAL REGISTRATION: Clinical Trial Gov number NCT02199093 . The protocol registration was received 23 July 2014. Participant enrollment began on 1 May 2014. The trial is expected to be completed in March 2016. PMID- 26542105 TI - Study on the kinetics and influence of feline platelet aggregation and deaggregation. AB - BACKGROUND: Feline platelets are prone to clumping after blood collection, rendering the determination of accurate platelet counts difficult for clinical laboratories and resulting in a high incidence of pseudothrombocytopenia in feline haematology reports. No information is available about the kinetics of platelet aggregate formation in feline ethylenediaminetetraacetic acid blood and the course of platelet counts over a clinically relevant time period. The aim of the present study was to determine platelet counts in healthy cats over a time period of 24 h after blood collection at 9 time points; to assess potential effects of platelet aggregates, anaesthesia and bleeding conditions on feline platelets and white blood cell counts; and finally, to investigate if glucose concentration is associated with the presence of aggregates. From 30 clinically healthy cats, blood samples were analysed at 9 different time points using two different haematology instruments (using fluorescence and impedance-based flow cytometry) in the counting chamber and by blood smear evaluation. RESULTS: Fourteen of the 30 samples were thrombocytopenic at one to 8 time points after collection as analysed on a fluorescence flow cytometry haematology analyser. At the 24-h timepoint, all thrombocytopenic samples had returned to normal platelet counts. Seventeen of the 30 samples showed platelet aggregates in the counting chamber. Significant differences in platelet counts were associated with the presence and size of aggregates and time since bleeding. No statistically significant differences in counts were found with regard to the quality of blood collection or the use of anaesthesia. Platelet aggregation and, therefore, pseudothrombocytopenia occurred in 57 % of the investigated samples at different time points. CONCLUSION: For the first time, deaggregation of feline platelet aggregates could be demonstrated as a reversible effect of platelet aggregation. For clinical laboratories or veterinarians, it may be helpful to rerun feline samples with pseudothrombocytopenia to obtain a more reliable platelet count. The quality of blood collection seems not to be causative for platelet aggregation. Blood smear evaluation is absolutely indicated in cases when haematology instruments give PLT counts below the reference interval. PMID- 26542106 TI - Nursing students' conception of clinical skills training before and after their first clinical placement: A quantitative, evaluative study. AB - Education institution and practice field have a joint responsibility with regard to facilitating a learning environment for the nursing students that provides learning outcomes in accordance with the National Curriculum. Using simulated patient situations is about ensuring a safe learning environment where mistakes are not putting real patients' lives in danger. THE AIM OF THE STUDY: To compare nursing students' experiences with a skills training situation immediately after the training and after their ten weeks clinical placement in nursing homes. STUDY DESIGN: Quantitative, cross-sectional and evaluative. SAMPLE: Full- and part-time students in their first year of a Bachelor of Nursing degree. The students answered a questionnaire on two different occasions, immediately after skills training and after internship in a nursing home. FINDINGS: Being a "patient" and a "nurse" in simulation was experienced as useful to clinical practice. Students with previous experience had a significantly higher perception of mastering the procedure after the internship, while unexperienced fellow students did not report any significant increase with regard to a sense of coping during their clinical practice. The findings raise questions if there are aspects with the education institution or the practice field that should be improved to help facilitate a better learning process for students without any previous experience. PMID- 26542107 TI - Let-7b-mediated pro-survival of transplanted mesenchymal stem cells for cardiac regeneration. AB - Stem cell-based repair and regeneration for cardiac regeneration following myocardial injury remain unmet challenges largely due to low viability of cells transplanted in the recipient sites. Accumulating evidence has revealed that local existence of reactive oxygen species (ROS) causes transplanted cell death via both apoptosis and autophagy. Ham and colleagues have identified let-7b as one of the primary mediators for ROS-induced apoptosis and autophagy of mesenchymal stem cells (MSCs) through direct targeting of caspase-3. Importantly, intramyocardial injection of let-7b-modified MSCs significantly enhanced ventricular function and facilitated myocardial repair by protecting transplanted cells from apoptosis and autophagy in the rat cardiac ischemia-reperfusion model. These findings provide novel insights into the roles of microRNA underlying stem cell survival following in vivo delivery, and offer further evidence that microRNA-modified MSC transplantation might be an effective therapeutic approach for tissue repair and regeneration. PMID- 26542108 TI - Colorimetric Humidity and Solvent Recognition Based on a Cation-Exchange Clay Mineral Incorporating Nickel(II)-Chelate Complexes. AB - Solvatochromic nickel(II) complexes with diketonato and diamine ligands were incorporated into a saponite clay by ion exchange, and their colorimetric humidity- and solvent-recognition properties were investigated. These powders exhibit color change from red to blue-green depending on humidity, and the detection range can be controlled by modifying the metal complex. The humidity response takes advantage of the humidity-dependent water content in clay and the coordination of water molecules to the metal complex in equilibrium. The addition of organic solvents to the powders causes a color change to occur, varying from red to blue-green depending on the donor number of the solvent, thereby enabling solvent recognition. In the clay, the affinity of less sterically hindered complexes to water or solvent molecules is decreased compared with that in solution because the cationic complexes interact with the anionic layers in the clay. Incorporating diethylene glycol into the materials produced thermochromic powders. PMID- 26542109 TI - Boosting AthaMap Database Content with Data from Protein Binding Microarrays. AB - The AthaMap database generates a map of predicted transcription factor binding sites (TFBS) and small RNA target sites for the whole Arabidopsis thaliana genome. With the advent of protein binding microarrays (PBM), the number of known TFBS for A. thaliana transcription factors (TFs) has increased dramatically. Using 113 positional weight matrices (PWMs) generated from a single PBM study and representing a total number of 68 different TFs, the number of predicted TFBS in AthaMap was now increased by about 3.8 * 10(7) to 4.9 * 10(7). The number of TFs with PWM-predicted TFBS annotated in AthaMap has increased to 126, representing a total of 29 TF families and newly including ARF, AT-Hook, YABBY, LOB/AS2 and SRS. Furthermore, links from all Arabidopsis TFs and genes to the newly established Arabidopsis Information Portal (AIP) have been implemented. With this qualitative and quantitative update, the improved AthaMap increases its value as a resource for the analysis of A. thaliana gene expression regulation at www.athamap.de. PMID- 26542110 TI - High-Level Accumulation of Triacylglycerol and Starch in Photoautotrophically Grown Chlamydomonas debaryana NIES-2212. AB - Microalgae have the potential to produce triacylglycerol (TAG) and starch, which provide alternative sources of biofuel. A problem in using Chlamydomonas reinhardtii as a model for TAG production has been that this alga lacks phosphatidylcholine (PC), which is thought to be important for TAG synthesis in plants. We found that C. debaryana is one of the rare species of Chlamydomonas having PC. Here we show that this strain, grown under complete photoautotrophic conditions, accumulated TAG and starch up to 20 and 250 pg per cell, respectively, during the stationary phase without nutrient deprivation. Addition of nutrients in this state did not cause loss of TAG, which was found in dilution with fresh medium. The photosynthetically produced TAG contained a high level of monounsaturated fatty acids, which is a preferred property as a material for biodiesel. The oil bodies were present in the cytoplasm, either between the cytoplasmic membrane and the chloroplast or between the chloroplast and the nucleus, whereas the starch granules were present within the chloroplast. Oil bodies were also deposited as a broad layer in the peripheral space of the cytoplasm outside the chloroplast, and might be easily released from the cells by genetic, chemical or mechanical manipulation. These results suggest that C. debaryana is a promising seed organism for developing a good biofuel producer. PMID- 26542112 TI - How fluorescent labelling alters the solution behaviour of proteins. AB - A complete understanding of the role of molecular anisotropy in directing the self assembly of colloids and proteins remains a challenge for soft matter science and biophysics. For proteins in particular, the complexity of the surface at a molecular level poses a challenge for any theoretical and numerical description. A soft matter approach, based on patchy models, has been useful in describing protein phase behaviour. In this work we examine how chemical modification of the protein surface, by addition of a fluorophore, affects the physical properties of protein solutions. By using a carefully controlled experimental protein model (human gamma-D crystallin) and numerical simulations, we demonstrate that protein solution behaviour defined by anisotropic surface effects can be captured by a custom patchy particle model. In particular, the chemical modification is found to be equivalent to the addition of a large hydrophobic surface patch with a large attractive potential energy well, which produces a significant increase in the temperature at which liquid-liquid phase separation occurs, even for very low fractions of fluorescently labelled proteins. These results are therefore directly relevant to all applications based on the use of fluorescent labelling by chemical modification, which have become increasingly important in the understanding of biological processes and biophysical interactions. PMID- 26542111 TI - Root ABA Accumulation in Long-Term Water-Stressed Plants is Sustained by Hormone Transport from Aerial Organs. AB - The reduced pool of the ABA precursors, beta,beta-carotenoids, in roots does not account for the substantial increase in ABA content in response to water stress (WS) conditions, suggesting that ABA could be transported from other organs. Basipetal transport was interrupted by stem-girdling, and ABA levels were determined in roots after two cycles of WS induced by transplanting plants to dry perlite. Leaf applications of isotope-labeled ABA and reciprocal grafting of ABA deficient tomato mutants were used to confirm the involvement of aerial organs on root ABA accumulation. Disruption of basipetal transport reduced ABA accumulation in roots, and this decrease was more severe after two consecutive WS periods. This effect was linked to a sharp decrease in the beta,beta-carotenoid pool in roots in response to water deficit. Significant levels of isotope-labeled ABA were transported from leaves to roots, mainly in plants subjected to water dehydration. Furthermore, the use of different ABA-deficient tomato mutants in reciprocal grafting combinations with wild-type genotypes confirmed the involvement of aerial organs in the ABA accumulation in roots. In conclusion, accumulation of ABA in roots after long-term WS periods largely relies on the aerial organs, suggesting a reduced ability of the roots to synthesize ABA from carotenoids. Furthermore, plants are able to transport ABA basipetally to sustain high hormone levels in roots. PMID- 26542113 TI - Exonuclease-Catalyzed Target Recycling Amplification and Immobilization-free Electrochemical Aptasensor. AB - A simple, sensitive, and selective immobilization-free electrochemical aptasensor had been developed which combines the advantages of the discrimination of the aggregation of long and short DNA on a negatively charged indium tin oxide (ITO) electrode, high selectivity of the aptamer, and high efficiency of exonuclease catalyzed target recycling amplification. Ochratoxin A (OTA), a type of mycotoxin, has been chosen as the model target. Methylene blue (MB) labeled probe DNA had been hybridized with the OTA aptamer first, which cannot diffuse freely to the negative charged ITO electrode surface due to the repulsion of the negative charges, since the hybridized DNA contains large negative charges. In the presence of target (OTA), the aptamer prefers to form an OTA-aptamer complex in lieu of an aptamer-DNA duplex, which results in the dissociation of probe DNA from the probe DNA-aptamer complex. The released probe DNA could be digested into mononucleotides, including a MB-labeled electroactive mononucleotide (eT), due to the employment of the RecJf exonuclease, a single-stranded DNA specific exonuclease. Since the eT contains little negative charge, it can diffuse easily to the negative charged ITO electrode surface, which results in the enhanced electrochemical response detected. At the same time, the aptamer in the OTA aptamer complex can be digested by RecJf exonuclease also to liberate the target, which can participate in the next reaction cycling and realize the electrochemical signal amplification. Based on this strategy, an ultrasensitive homogeneous immobilization-free electrochemical aptasensor for OTA can be developed with a low detection limit (LOD) of 0.004 ng mL(-1) (S/N = 3). The proposed biosensor combines the advantages of the simplicity of immobilization free homogeneous ITO based electrochemical determination, high efficiency of exonuclease-catalyzed target recycling, and high selectivity of the aptamer. The fabricated biosensor has been applied to detect OTA in real samples with satisfactory results. The same strategy can be applied to develop biosensors for diverse targets. PMID- 26542114 TI - In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia. AB - BACKGROUND: Although progress in children, in adults, ALL still carries a dismal outcome. Here, we explored the in vitro and in vivo activity of PF-00477736 (Pfizer), a potent, selective ATP-competitive small-molecule inhibitor of checkpoint kinase 1 (Chk1) and with lower efficacy of checkpoint kinase 2 (Chk2). METHODS: The effectiveness of PF-00477736 as single agent in B-/T-ALL was evaluated in vitro and in vivo studies as a single agent. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B-/T-ALL cell lines. Finally, the action of PF-00477736 was assessed in vivo using leukemic mouse generated by a single administration of the tumorigenic agent N-ethyl-N-nitrosourea. RESULTS: Chk1 and Chk2 are overexpressed concomitant with the presence of genetic damage as suggested by the nuclear labeling for gamma-H2A.X (Ser139) in 68 % of ALL patients. In human B- and T-ALL cell lines, inhibition of Chk1/2 as a single treatment strategy efficiently triggered the Chk1-Cdc25-Cdc2 pathway resulting in a dose- and time-dependent cytotoxicity, induction of apoptosis, and increased DNA damage. Moreover, treatment with PF-00477736 showed efficacy ex vivo in primary leukemic blasts separated from 14 adult ALL patients and in vivo in mice transplanted with T-ALL, arguing in favor of its future clinical evaluation in leukemia. CONCLUSIONS: In vitro, ex vivo, and in vivo results support the inhibition of Chk1 as a new therapeutic strategy in acute lymphoblastic leukemia, and they provide a strong rationale for its future clinical investigation. PMID- 26542115 TI - Infection control knowledge, beliefs and behaviours amongst cystic fibrosis patients with epidemic Pseudomonas aeruginosa. AB - BACKGROUND: Epidemic P. aeruginosa (ePA) infections are common in cystic fibrosis (CF) and have been associated with accelerated clinical decline. Factors associated with ePA are unclear, and evidence based infection control interventions are lacking. METHODS: We prospectively collect all bacterial pathogens from adult CF patients. We performed PA strain typing on retrospectively collected enrollment samples and recent isolates to identify patients infected with ePA. All patients attending our clinic were approached to complete a survey on infection control knowledge, beliefs and exposures. We analyzed responses of those with ePA relative to the entire cohort without ePA as well as those infected with unique strains of P. aeruginosa to assess for risk factors for ePA and differences in infection control knowledge, beliefs or behaviours. RESULTS: Of 144 participants, 30 patients had ePA (two Liverpool epidemic strain, 28 Prairie epidemic strain), 83 % of which had established infection prior to transition to the adult clinic. Risk of concomitant infecting pathogens was no different between groups although, Staphylococcus aureus and non tuberculous mycobacteria were less common in those with ePA. Patients with ePA were more likely to have attended CF-camp and have a history of CF fundraising. Patients with ePA did not differ with respect to beliefs regarding pathogens or transmission risk, except they believed indirect contact posed little risk. Furthermore, patients with ePA were more likely to continue to associate with others with CF despite extensive counselling. Use of peer-peer online networking was minimal in both groups. CONCLUSION: Infections with ePA are closely linked to past exposures, now routinely discouraged. As socialization is the greatest risk factor for ePA, infection control strategies for ePA must focus on discouraging face-to-face interactions amongst CF patients. As peer support remains a desire amongst patients, investment in technologies and strategies that enable indirect communication and support are required. PMID- 26542116 TI - Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12. AB - BACKGROUND: High risk medications are commonly prescribed to older US patients. Currently, less is known about high risk medication prescribing in other Western Countries, including the UK. We measured trends and correlates of high risk medication prescribing in a subset of the older UK population (community/institutionalized) to inform harm minimization efforts. METHODS: Three cross-sectional samples from primary care electronic clinical records (UK Clinical Practice Research Datalink, CPRD) in fiscal years 2003/04, 2007/08 and 2011/12 were taken. This yielded a sample of 13,900 people aged 65 years or over from 504 UK general practices. High risk medications were defined by 2012 Beers Criteria adapted for the UK. Using descriptive statistical methods and regression modelling, prevalence of 'any' (drugs prescribed at least once per year) and 'long-term' (drugs prescribed all quarters of year) high risk medication prescribing and correlates were determined. RESULTS: While polypharmacy rates have risen sharply, high risk medication prevalence has remained stable across a decade. A third of older (65+) people are exposed to high risk medications, but only half of the total prevalence was long-term (any = 38.4 % [95 % CI: 36.3, 40.5]; long-term = 17.4 % [15.9, 19.9] in 2011/12). Long-term but not any high risk medication exposure was associated with older ages (85 years or over). Women and people with higher polypharmacy burden were at greater risk of exposure; lower socio-economic status was not associated. Ten drugs/drug classes accounted for most of high risk medication prescribing in 2011/12. CONCLUSIONS: High risk medication prescribing has not increased over time against a background of increasing polypharmacy in the UK. Half of patients receiving high risk medications do so for less than a year. Reducing or optimising the use of a limited number of drugs could dramatically reduce high risk medications in older people. Further research is needed to investigate why the oldest old and women are at greater risk. Interventions to reduce high risk medications may need to target shorter and long-term use separately. PMID- 26542117 TI - Pain, instability, and familial discord: a qualitative study into women who use drugs in Malaysia. AB - BACKGROUND: Out of 20,887 persons who use drugs that came into contact with the National Anti-Drugs Agency (NADA) officials in the year 2013, 3.2% were women. Because women who use drugs (WWUD) are often a hidden population, this may be an underestimate. International literature shows that women who use drugs face increased risk of HIV, intimate partner violence, and mental health issues. Similar literature in Malaysia is lacking, and thus, the objective of our study was exploratory in nature. METHODS: Thirty-eight women who use drugs were interviewed using a semi-structured topic guide in Kelantan, Penang, Johor, Kuala Lumpur, and Selangor. Locations were chosen purposively. Nineteen women were interviewed individually and the remaining 19 were in focus group discussions (FGDs). All interviews were transcribed verbatim, translated to English, and analyzed with NVivo. RESULTS: Median age of respondents was 35.5 years old, 89.5% ethnic Malays, majority having married below the age of 20, and were of low socioeconomic backgrounds. Youngest age of initiation into drug use was 9 years old. Most reported is inhalation of amphetamine-type substances. Seven reported ever injecting. Three themes emerged: (a) repeating patterns of fluid family structures and instability; (b) "pain" and "difficulty" as features of home life; and (c) seeking marriage as a source of stabilization and practices of power within those marriages. Respondents often came from very fluid family environments and married to find stability, only to be drawn into a similar cycle. None of the women who had been separated from their children either institutionally, by family members, or by third parties, had accessed legal recourse for the loss of their parental rights. CONCLUSION: Unstable familial relationships or environments contributed to earlier initiation of drug use which raised questions about support services for WWUD and children who use drugs. Respondents were drawn into unstable and/or abusive relationships, perpetuating social inequalities that marked their own familial environments during childhood. These findings support the need for additional services to support the unique needs of WWUD, including domestic violence services, financial and life skills, parental rights assistance, and empowerment programs. PMID- 26542118 TI - Acute loss of vision after an intravitreal injection ocriplasmin: a functional evolutionary study for 1-year follow-up. AB - INTRODUCTION: Ocriplasmin is a human plasmin fragment indicated for vitreomacular traction treatment. With its increasing use, several reported cases have suggested possible toxicity to the retina. CASE: We describe a case of a 55-year old woman with symptomatic vitreomacular traction and a macular hole in the right eye who showed an acute decrease in visual acuity after an intravitreal ocriplasmin injection. Spectral-domain optical coherence tomography showed an alteration in the ellipsoid layer. Significant retinal vessel constriction was observed by angiography. The visual acuity improved to 20/100, and the electroretinogram progressively improved after the 1-year follow-up and following pars plana vitrectomy. CONCLUSIONS: A decrease in visual acuity and an enlargement of the macular hole were observed while studying this patient. This study shows the recovery of adverse effects caused by intravitreal injection of ocriplasmin for 1-year follow-up. PMID- 26542119 TI - Performance of the Orsiro Hybrid drug-eluting stent in high-risk subgroups. AB - Newer-generation drug-eluting stents (DES) with enhanced biocompatibility that deliver antiproliferative drugs from a durable polymer have significantly improved safety and efficacy outcomes, compared with both early-generation DES and bare-metal stents, and they represent the current standard of care in all patient and lesion subsets. However, newer durable polymers have been associated with the occurrence of chronic inflammation, delayed vascular healing, incomplete endothelialisation, and neoatherosclerosis, which may result in persistent late adverse cardiovascular events, particularly in patients with high-risk baseline clinical features and angiographic complex coronary artery disease. Newer generation DES with biodegradable polymer and controlled drug release have been recently introduced to overcome long-term adverse outcomes observed with both early-generation and newer-generation permanent polymer-based DES, and they may be of incremental clinical value in subgroups of patients at higher risk of stent failure. The recent ultrathin-strut cobalt-chromium Orsiro Hybrid DES (BIOTRONIK AG, Bulach, Switzerland) eluting sirolimus from a biodegradable polymer was designed to improve arterial healing and clinical outcomes. The Orsiro Hybrid DES has demonstrated clinical performance comparable to the current state-of-the-art newer-generation thin-strut cobalt-chromium, permanent polymer-based everolimus eluting stent in a broad patient population. In subgroups of patients at highest risk of adverse ischemic events, such as patients with diabetes mellitus, small vessels, long lesions, complex coronary lesions, multivessel disease, chronic total occlusion, or ST-segment elevation myocardial infarction, the Orsiro Hybrid DES has shown low rates of adverse clinical outcomes, similar to rates observed in lower-risk patients, and extremely low rates of definite stent thrombosis. This article reviews current evidence on safety and efficacy of the recent ultrathin-strut biodegradable polymer Orsiro Hybrid DES in high-risk subgroups. PMID- 26542120 TI - A new principle for the standardization of long paragraphs for reading speed analysis. AB - PURPOSE: To investigate the reliability, validity, and statistical comparability of long paragraphs that were developed to be equivalent in construction and difficulty. METHODS: Seven long paragraphs were developed that were equal in syntax, morphology, and number and position of words (111), with the same number of syllables (179) and number of characters (660). For validity analyses, the paragraphs were compared with the mean reading speed of a set of seven sentence optotypes of the RADNER Reading Charts (mean of 7 * 14 = 98 words read). Reliability analyses were performed by calculating the Cronbach's alpha value and the corrected total item correlation. Sixty participants (aged 20-77 years) read the paragraphs and the sentences (distance 40 cm; font: Times New Roman 12 pt). Test items were presented randomly; reading length was measured with a stopwatch. RESULTS: Reliability analysis yielded a Cronbach's alpha value of 0.988. When the long paragraphs were compared in pairwise fashion, significant differences were found in 13 of the 21 pairs (p < 0.05). In two sequences of three paragraphs each and in eight pairs of paragraphs, the paragraphs did not differ significantly, and these paragraph combinations are therefore suitable for comparative research studies. The mean reading speed was 173.34 +/- 24.01 words per minute (wpm) for the long paragraphs and 198.26 +/- 28.60 wpm for the sentence optotypes. The maximum difference in reading speed was 5.55 % for the long paragraphs and 2.95 % for the short sentence optotypes. The correlation between long paragraphs and sentence optotypes was high (r = 0.9243). CONCLUSIONS: Despite good reliability and equivalence in construction and degree of difficulty, a statistically significant difference in reading speed can occur between long paragraphs. Since statistical significance should be dependent only on the persons tested, either standardizing long paragraphs for statistical equality of reading speed measurements or increasing the number of presented paragraphs is recommended for comparative investigations. PMID- 26542121 TI - Spectral-domain optical coherence tomography findings of tractional retinal elevation in patients with diabetic retinopathy. AB - PURPOSE: To evaluate the clinical and morphological characteristics as well as the surgical outcomes of tractional retinal elevation (TRE) in patients with proliferative diabetic retinopathy (PDR) by analyzing spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT images of 26 eyes (24 patients) who visited our clinic because of TRE and PDR from August 2011 to August 2014 were reviewed. According to the presence or absence of tractional retinal detachment (TRD), patients were classified into group 1 (without TRD) or group 2 (with TRD), and the clinical characteristics and surgical outcomes of the two groups were compared. Furthermore, we categorized the SD-OCT morphological components into sponge, cystoid, saw tooth, bridging columnar, and TRD and compared the characteristics among patients who had different components. RESULTS: Group 1 had 18 eyes and group 2 had eight eyes. No differences in age, best corrected visual acuity (BCVA), or spherical equivalent were observed between the two groups, but group 2 had longer axial length than that of group 1 (p = 0.02). A large variety of combined OCT findings was found in group 1 compared to that in group 2. TRD was the least combined form with the other morphological components. Although 92 % of eyes with the bridging columnar component had the cystoid component, TRD and tractional retinoschisis (TRS, bridging columnar morphology) were combined in only one eye. CONCLUSION: Diabetic TRE may progress to TRD or TRS, which are mutually exclusive. They may progress to TRD in eyes with a long axial length, and cystoid macular edema seems to develop into TRS. PMID- 26542122 TI - Impaired systemic vascular endothelial function in patients with non-arteritic anterior ischaemic optic neuropathy. AB - PURPOSE: The purpose of this study was to evaluate systemic endothelial function in elderly hypertension patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using a noninvasive physiological method: endothelium dependent, flow-mediated vasodilation (FMD). METHODS: Forty-two systemic hypertension patients with NAION (NAION group), 64 age- and sex-matched patients with systemic hypertension and no other ocular disease (hypertension group), and 100 age- and sex-matched healthy volunteers (normal group) were enrolled. FMD was evaluated using a high-resolution ultrasonography. Traditional cardiovascular risk factors and vascular parameters were measured. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in patients with NAION compared with the control groups (p < 0.001). The FMD decreased significantly in the NAION group (6.02 +/- 1.87 %) compared to in the hypertension group (7.86 +/- 2.94 %, p < 0.001) and the normal group (8.99 +/- 2.44 %, p < 0.001). By multivariable logistic regression analysis, FMD was significantly associated with NAION (OR, 1.79; 95%CI, 1.67-2.01). CONCLUSIONS: NAION may be associated with systemic vascular endothelial dysfunction. FMD might be useful in the treatment monitoring of NAION. PMID- 26542123 TI - Collective learning modeling based on the kinetic theory of active particles. AB - This paper proposes a systems approach to the theory of perception and learning in populations composed of many living entities. Starting from a phenomenological description of these processes, a mathematical structure is derived which is deemed to incorporate their complexity features. The modeling is based on a generalization of kinetic theory methods where interactions are described by theoretical tools of game theory. As an application, the proposed approach is used to model the learning processes that take place in a classroom. PMID- 26542124 TI - Crosstalk between exercise and galanin system alleviates insulin resistance. AB - Studies have demonstrated that aerobic exercise can enhance insulin sensitivity, however, the precise mechanism for this outcome is not entirely identified. Emerging evidences point out that exercise can upregulate galanin protein and mRNA expression, resulting in improvement of insulin sensitivity via an increase in translocation of glucose transporter 4 and subsequent glucose uptake in myocytes and adipocytes of healthy and type 2 diabetic rats, which may be blocked by galanin antagonist. In return, galanin can exert the exercise-protective roles to prevent excessive movement of skeletal muscle and to accelerate exercise trauma repair in exercise-relative tissues. Studies also implicated that combination of aerobic exercise and activation of galanin system may make more significant improvement in insulin sensitivity than that of either one did. These suggest that galanin system is essential for physical activity to alleviate insulin resistance, namely, the beneficial effect of physical activity on glucose uptake is at least partly mediated by galanin system. Besides, co-treatment with galanin and exercise is an effective therapeutic strategy for reducing insulin resistance. PMID- 26542125 TI - The upper respiratory tract is a natural reservoir of haemolytic Mannheimia species associated with ovine mastitis. AB - Lamb suckling has been suggested to be an important way of infecting a ewe's udder with different bacteria, including Mannheimia haemolytica. To test the potential role of lambs in transferring Mannheimia species to the ewe's udder, the restriction endonuclease cleavage patterns of isolates obtained from nasopharyngeal swabs were compared with those obtained from cases of mastitis. Sterile cotton swabs were used to collect nasopharyngeal samples from 50 ewes and 36 lambs from three flocks. M. haemolytica and Mannheimia glucosida as well as haemolytic Mannheimia ruminalis-like organisms were detected in the upper respiratory tract of lambs and ewes. Comparison of the restriction endonuclease cleavage patterns of the isolates suggested that the M. haemolytica isolates obtained from different milk samples from ewes with mastitis were more clonal than those obtained from the nasal swabs. However, some nasal isolates within both Mannheimia species had restriction endonuclease cleavage patterns identical to those obtained from milk samples from ewes with mastitis, indicating that lambs may have a role in transferring these organisms to the udder. More clonality was observed between the M. glucosida isolates than between M. haemolytica isolates. PMID- 26542126 TI - Effects of Thiazolidinediones on metabolism and cancer: Relative influence of PPARgamma and IGF-1 signaling. AB - Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists. TZDs are orally effective medicines for metabolic syndrome and type 2 diabetes. In addition to metabolic effects these molecules also possess anti-cancer effects. Data from diabetes clinical trials also support anti cancer effects of TZDs. The anti-cancer effects of TZDs neither correlate well with their ability to activate PPARgamma receptor, nor are affected by the presence of PPARgamma receptor antagonists. Accumulating evidence suggests that TZDs act as selective inhibitors of insulin-like growth factor-1 (IGF-1) receptor signaling, and IGF-1 signaling is known to be aberrantly regulated in various cancers. Structural analysis of TZDs suggest that the presence of 5-exo C-C single bond of the thiazolidine-2,4-dione ring is important for the metabolic effects but not for anti-cancer effects, as inclusion of C=C double bond at this position promotes antagonistic properties to the PPARgamma receptor without compromising its anti-proliferative effects. The objectives of this review includes summarization of the relative influence of TZDs on PPARgamma and IGF-1 signaling in mediating pharmacological effects, and to discuss the possibility of multiple pharmacophores, and thereby independent regulation of PPARgamma and IGF 1 signaling. PMID- 26542128 TI - [Not Available]. PMID- 26542127 TI - The Southwestern fringe of Europe as an important reservoir of caprine biodiversity. AB - BACKGROUND: Portugal and Spain, with six and 22 officially recognized caprine breeds, encompass 25 % of the European Union goat census. Many of these populations have suffered strong demographic declines because of competition with exotic breeds and the phasing-out of low income rural activities. In this study, we have investigated the consequences of these and other demographic processes on the genetic diversity, population structure and inbreeding levels of Iberian and Atlantic goats. METHODS: A sample of 975 individuals representing 25 officially recognized breeds from Portugal and Spain, two small populations not officially recognized (Formentera and Ajui goats) and two ecotypes of the Tinerfena and Blanca Celtiberica breeds were genotyped with a panel of 20 microsatellite markers. A wide array of population genetics methods was applied to make inferences about the genetic relationships and demography of these caprine populations. RESULTS: Genetic differentiation among Portuguese and Spanish breeds was weak but significant (FST = 0.07; P < 0.001), which is probably the consequence of their short splitting times and extensive gene flow due to transhumance. In contrast, Canarian goats were strongly differentiated because of prolonged geographic isolation. Most populations displayed considerable levels of diversity (mean He = 0.65). CONCLUSIONS: High diversity levels and weak population structures are distinctive features of Portuguese and Spanish breeds. In general, these local breeds have a reduced census, but are still important reservoirs of genetic diversity. These findings reinforce the need for the implementation of management and breeding programs based on genetic data in order to minimize inbreeding, maintain overall genetic and allelic diversities and breed identities, while at the same time taking into account the within-breed genetic structure. PMID- 26542129 TI - Length of abdominal aortic aneurysm and incidence of endoleaks type II after endovascular repair. AB - OBJECTIVE: To evaluate the predicting factors for the development of endoleak type II, its frequency and influencing factors after elective endovascular repair (EVAR) of infrarenal abdominal aortic aneurysms (AAA). METHODS: Data were prospectively collected in a unicenter observational study (tertiary center of [endo-] vascular surgery) and retrospectively evaluated in patients who had undergone elective EVAR of AAA. Vascular (lumbar arteries (LA) and inferior mesenteric artery, aneurysm) and general patient (habits, medication, basic diseases) as well as procedural characteristics, were analyzed for their association with the development of endoleak type II. Pre and postinterventional computed tomography (CT) scans were evaluated for aneurysm anatomy, in particular, postinterventional growth or shrinkage as well detection of an endoleak of each type. RESULTS: The study cohort included 82 patients (mean age, 72 (52-87) years; 77 men, 93.9%) throughout 36 months. The median follow-up period was 29.5 months (range, 1-57). Overall, 51 endoleaks type II (62.2%) were identified at any time during the postinterventional follow-up period. In the Cox regression, AAA length was the only significant predictor (P = 0.024; hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.01-1.14). Thirteen patients (15.8%) underwent at least one secondary intervention. Aneurysm growth was observed in four patients because of an endoleak type II (4.9%). No AAA rupture occurred in association with an isolated endoleak type II. CONCLUSION: The preoperative AAA length (correlating with the number of LA) can be considered a risk factor for postinterventional occurrence of endoleak type II prompting to greater attention and possible preemptive therapy. PMID- 26542130 TI - Thelazia callipaeda--first human case of thelaziosis in Croatia. AB - A case of the first ocular thelaziosis in a human male patient in Croatia is presented. Thelaziosis is a zoonosis caused by the nematodes of the genus Thelazia. In all, two types of the genus have been described as causes of infection in humans, Thelazia callipaeda and Thelazia californiensis. This zoonosis, called "oriental eye worm" is very rare in humans in European countries, with high incidence in Asian countries, especially in China, Thailand, and Japan. PMID- 26542131 TI - Case fatality rate related to nosocomial and ventilator-associated pneumonia in an ICU: a single-centre retrospective cohort study. AB - BACKGROUND: Nosocomial pneumonia (NP) and ventilator associated pneumonia (VAP) have been associated with financially significant economic burden and increased case fatality rate in adult intensive care units (ICUs). This study was designed to evaluate case fatality rate among patients with NP and VAP in a respiratory ICU. METHODS: In 2008-2013, VAP and NP in the ICUs were included in this retrospective single-centre cohort study. Data on demographics, co-morbidities, severity of illness, mechanical ventilation, empirical treatment, length of hospital stay and laboratory findings were recorded in each group, as were case fatality rate during ICU admission and after discharge including short-term (28 day) and long-term (a year) case fatality rate. RESULTS: A total of 108 patients with VAP (n = 64, median (IQR) age: 70 (61-75) years, 67.2% were men) or NP (n = 44, median (IQR) age: 68 (62-74) years, 68.2% were men) were found. Appropriate empirical antibiotic therapy was identified only in 45.2 and 42.9% of patients with VAP and NP, respectively. Overall case fatality rate in VAP and NP (81.3 vs 84.1), ICU case fatality rate (42.2 vs 45.5%), short-term case fatality rate (15.6 vs 27.3%) and long-term case fatality rate (23.4 vs 11.4%) were similar between VAP and NP groups along with occurrence 50% of case fatality rate cases in the first 2 months and 90% within the first year of discharge. Multivariate analysis showed that chronic obstructive pulmonary disease (COPD) (HR: 3.15, 95% CI: 1.06-9.38; p = 0.039) and presence of septic shock (HR: 3.83, 95% CI: 1.26 11.60; p = 0.018) were independently associated with lower survival. CONCLUSION: In conclusion, our findings in a retrospective cohort of respiratory ICU patients with VAP or NP revealed high ICU, short- and long-term case fatality rates within 1 year of diagnosis, regardless of the diagnosis of NP after 48 h of initial admission or after induction of ventilator support. COPD and presence of septic shock are associated with high fatality rate and our findings speculate that as increasing compliance with infection control programs and close monitoring especially in 2 months of discharge might reduce high-case fatality rate in patients with VAP and NP. PMID- 26542132 TI - Case report: spontaneous rupture of spleen in patient with Plasmodium ovale malaria. AB - Malaria may lead to spontaneous splenic rupture as a rare but potentially lethal complication. Most frequently, this has been reported in patients infected with Plasmodium falciparum and Plasmodium vivax, while other parasitic agents are less likely to be the cause.We report a 29-year-old British Caucasian, who after returning from a business trip in Democratic Republic Congo was diagnosed with tertian malaria caused by Plasmodium ovale.During his in-patient stay, the patient suffered a splenic rupture requiring immediate surgical intervention and splenectomy. Following this surgical intervention, there was an uneventful recovery, and the patient was discharged in a good general condition. PMID- 26542134 TI - Putative embryonic stem cells derived from porcine cloned blastocysts using induced pluripotent stem cells as donors. AB - The establishment of porcine embryonic stem cells (ESCs) would have great impact in biomedical studies and preclinical trials through their use in genetic engineering. However, authentic porcine ESCs have not been established until now. In this study, a total of seven putative ESC lines were derived from porcine embryos of various origins, including in vitro fertilization, parthenogenetic activation, and, in particular, induced pluripotent stem (iPS) nuclear transfer (NT) from a donor cell with induced pluripotent stem cells (iPSCs). To characterize these cell lines, several assays including an assessment of intensive alkaline phosphatase activity, karyotyping, embryoid body formation, expression analysis of the pluripotency-associated markers, and the three germ layerassociated markers were performed. Based on quantitative polymerase chain reaction, the expression levels of REX1 and FGFR2 in iPS-NT lines were higher than those of cells of other origins. Additionally, only iPS-NT lines showed multiple aberrant patterns of nuclear foci elucidated by immunofluorescence staining of H3K27me3 as a marker of the state of X chromosome inactivation and a less mature form of mitochondria like naive ESCs, by transmission electron microscopy. Together, these data suggested that established putative porcine ESC lines generally exhibited a primed pluripotent state, like human ESCs. However, iPS-NT lines have especially unique characteristics distinct from other origins because they have more epigenetic instability and naive-like mitochondrial morphology than other putative ESC lines. This is the first study to establish and characterize the iPSC-derived putative ESC lines and compare them with other lines derived from different origins in pigs. PMID- 26542133 TI - Monocytes and monocyte chemoattractant protein 1 (MCP-1) as early predictors of disease outcome in patients with cerebral ischemic stroke. AB - In this study to identify prognostic biomarkers for ischemic stroke (IS) outcome, we monitored monocyte number and monocyte chemoattractant protein (MCP-1) concentration in peripheral blood of 44 patients with IS during the week following IS. According to the severity of IS, patients were allocated to three groups: patients with transient ischemic attack (TIA), patients with National Institute of Health Stroke Scale (NIHSS) score <= 12, and patients with NIHSS > 12. In patients with NIHSS > 12 statistically significant increased number of monocytes was observed on day 7. MCP-1 plasma concentration initially increased, decreased at day 3 in patients with NIHSS > 12 and increased and restored on day 7. A negative correlation between the number of monocytes and MCP-1 concentration was observed on day 3 after IS. Higher day-7 MCP-1 level was associated with higher modified Rankin Scale (mRS) value (indicating worse outcome) at 90 days post-IS in patients with NIHSS > 12. Our findings suggest that number of monocytes and plasma MCP-1 level could be clinical prognostic biomarkers as early predictors of disease outcome in patients with IS. PMID- 26542135 TI - The tolerance of feline corpus and cauda spermatozoa to cryostress. AB - Epididymal sperm preservation can be used to avoid the total loss of genetic material in threatened species. Spermatozoa from the corpus, as from the cauda, are motile and can undergo capacitation. Thus, they can potentially be preserved for assisted reproductive technologies. However, cryopreservation of spermatozoa has a direct detrimental effect on sperm quality. The aim of this study was to compare the chromatin stability and the survival rate of spermatozoa from the corpus and cauda epididymis after cryopreservation. Epididymal spermatozoa were collected and cryopreserved from the corpus and cauda of 12 domestic cats. Sperm motility, progressive motility, membrane integrity, acrosome integrity, and DNA integrity were evaluated before and after freezing thawing. The average total number of spermatozoa collected from the corpus was lower (10.2 * 10(6) +/- 7.4) than that from the cauda epididymis (24.9 * 10(6) +/- 14.4; P = 0.005). The percentage of spermatozoa with intact DNA did not differ significantly whether it was collected from the corpus or cauda regions and did not decrease after freezing thawing in either region. However, motility of spermatozoa from both regions was affected by the freezing thawing process with a significant decline in motility after thaw compared with fresh spermatozoa. A significant difference in the percentage of motile sperm between the corpus and cauda was observed after the freezing thawing process (P < 0.001). Although sperm motility was lower in postthaw spermatozoa from the corpus epididymidis than from the cauda, the rate of the reduction did not differ between regions. This study indicates that the cryopreservation process does not have a negative effect on chromatin stability of feline epididymal spermatozoa. Spermatozoa from the corpus region have a similar freezability as spermatozoa from the cauda region. Therefore, preservation of spermatozoa from the corpus and the cauda epididymidis might be of value in preserving genetic material from endangered or valuable felids. PMID- 26542136 TI - Impact of spontaneous Neospora caninum infection on pregnancy loss and subsequent pregnancy in grazing lactating dairy cows. AB - The impact of spontaneous Neospora caninum infection on pregnancy loss and subsequent pregnancy in grazing lactating dairy cows was evaluated. Data from 1273 females (878 multiparous and 395 first-calving cows) from six preselected dairy herds were analyzed. Cows were classified as seropositive (SP) (prevalence, 24%; range, 11%-33%) or seronegative (SN) by indirect immunofluorescence detection of antibodies against N caninum. Seropositive cows (prevalence, 40.0%) presented higher (P < 0.001) incidence of abortion compared with SN cows (prevalence, 4.1%). Neospora caninum DNA was detected by real-time polymerase chain reaction in 44.4% of intact aborted fetuses from SP cows, whereas none was found in those aborted from SN cows. The average daily milk production adjusted to 305 days was lower (P < 0.001) in SP (22.5 +/- 0.3 L/day) than in SN cows (24.8 +/- 0.2 L/day). Furthermore, SP cows presented greater occurrence of retained placenta (17.1% vs. 6.0%; P < 0.001) and acute postpartum metritis (9.8% vs. 2.4%; P < 0.001). Despite similar pregnancy rates after first postpartum artificial insemination (27.6% vs. 31.8%; P = 0.40), cumulative pregnancy rates during 300 days in milk (94.7% vs. 98.5%; P = 0.005) were greater in SN cows. A reduced (P = 0.0001) Cox proportional hazard of pregnancy rate at 300 days in milk and a longer interval from parturition or abortion to conception (median, 111 vs. 101 days) were observed in SP compared with SN cows. Spontaneous N caninum infection is a significant contributing factor of pregnancy loss and occurrence of uterine disease (i.e., retained placenta and metritis), negatively affecting subsequent pregnancy in grazing lactating dairy cows. PMID- 26542137 TI - L-ergothioneine supplementation during culture improves quality of bovine in vitro-produced embryos. AB - The aim of this study was to evaluate whether supplementation of bovine culture medium with the natural antioxidant L-ergothioneine (LE), improves in vitro blastocyst development and quality, assessed as resistance to cryopreservation, total cells number, cellular differentiation, and apoptosis index. Abattoir derived oocytes were matured and fertilized in vitro according to standard procedure. Twenty hours after IVF, presumptive zygotes were cultured in synthetic oviduct fluid with 0, 0.05 mM, 0.1 mM, 0.5 mM, and 1 mM of LE (experiment 1) at 39 degrees C under humidified air with 5% CO2, 7% O2, and 88% N2. On the basis of the results of this dose-response trial, the range of concentrations to test was reduced in experiment 2, in which presumptive zygotes were cultured with 0, 0.05 mM, and 0.1 mM of LE. On Day 7, embryo yields were assessed, and the blastocysts (BL) were vitrified by Cryotop method in 16.5% ethylene glycol, 16.5% DMSO and 0.5 M sucrose. Finally, BL produced on Day 8 in the absence (control) and presence of 0.1 mM LE were used for transferase-mediated dUTP nick end labeling and differential staining to evaluate, respectively the apoptotic rate and the allocation of cells into inner cell mass (ICM) and trophectoderm lineages (experiment 3). Despite similar blastocyst yields, supplementation of culture medium with 0.1 mM LE improved the cryotolerance of in vitro-produced (IVP) embryos compared to the control group, as indicated by higher (P < 0.05) hatching rates recorded after 48-hour post-warming culture (48.5%, 50.0%, and 63.8%, respectively with 0, 0.05, and 0.1 mM LE). Interestingly, when embryos were cultured in the presence of 0.1 mM LE, the percentage of BL with the most physiological ICM:total cells ratio (20%-40%) increased (85.1 vs. 66.0%, P < 0.05), confirming a beneficial effect on embryo quality. Furthermore, 0.1 mM LE decreased (P < 0.01) both the average number (4.3 +/- 0.2 vs. 9.1 +/- 0.3) and the proportion (3.6 +/- 0.3 vs. 8.1 +/- 0.5) of apoptotic cells in BL compared to the control. In conclusion, the enrichment of bovine culture medium with 0.1 mM LE improves embryo quality, as indicated by the improved cryotolerance, the lower apoptotic rate, and the higher percentage of BL with the most physiological ICM:total cells ratio. PMID- 26542138 TI - Identification and profiling of microRNAs in the ovaries of polytocous and monotocous goats during estrus. AB - MicroRNAs (miRNAs) play critical roles in almost all ovarian biological processes, including folliculogenesis, ovulation, luteal development, and regression. The study identified known and novel miRNAs in the ovaries of polytocous and monotocous goats by combining Solexa sequencing with bioinformatics. In total, 862 known and 53 novel miRNAs were identified in the ovaries of polytocous and monotocous goats. A total of 771 miRNAs were co expressed in both libraries. One hundred twenty miRNAs in the ovaries of polytocous goats and 24 miRNAs in the ovaries of monotocous goats were specifically expressed. In addition, 445 miRNAs were differentially expressed in the ovaries of polytocous and monotocous goats, of which 348 were upregulated, and 97 were downregulated in the ovaries of polytocous goats compared with the ovaries of monotocous goats (P values < 0.05 and |log2 (fold change)|> 1). The expression levels of 12 randomly selected miRNAs were analyzed by stem-loop real time quantitative polymerase chain reaction, and the results demonstrated that the expression patterns were consistent with Solexa sequencing results. KEGG analysis showed that GnRH, transforming growth factor-beta, vascular endothelial growth factor, and mammalian target of rapamycin signaling pathways, oocyte meiosis and ovarian steroidogenesis participated in follicular development and ovulation. On the basis of miRNA-mRNA network analysis and luciferase reporter assays, the ggo-miR-4488-p3_1ss10CG, bta-miR-2892-p5_1ss8CG and hsa-miR-4532_L+1R 3 were closely related with prolific traits. The results will help to further understand the role of miRNAs in kidding rate regulation. PMID- 26542139 TI - Drag reduction effects facilitated by microridges inside the mouthparts of honeybee workers and drones. AB - The mouthpart of a honeybee is a natural well-designed micropump that uses a reciprocating glossa through a temporary tube comprising a pair of galeae and labial palpi for loading nectar. The shapes and sizes of mouthparts differ among castes of honeybees, but the diversities of the functional microstructures inside the mouthparts of honeybee workers and drones remain poorly understood. Through scanning electron microscopy, we found the dimensional difference of uniformly distributed microridges on the inner galeae walls of Apis mellifera ligustica workers and drones. Subsequently, we recorded the feeding process of live honeybees by using a specially designed high-speed camera system. Considering the microridges and kinematics of the glossa, we constructed a hydrodynamic model to calculate the friction coefficient of the mouthpart. In addition, we test the drag reduction through the dimensional variations of the microridges on the inner walls of mouthparts. Theoretical estimations of the friction coefficient with respect to dipping frequency show that inner microridges can reduce friction during the feeding process of honeybees. The effects of drag reduction regulated by specific microridges were then compared. The friction coefficients of the workers and drones were found to be 0.011+/-0.007 (mean+/-s.d.) and 0.045+/ 0.010, respectively. These results indicate that the mouthparts of workers are more capable of drag reduction compared with those of drones. The difference was analyzed by comparing the foraging behavior of the workers and drones. Workers are equipped with well-developed hypopharyngeal, and their dipping frequency is higher than that of drones. Our research establishes a critical link between microridge dimensions and drag reduction capability during the nectar feeding of honeybees. Our results reveal that microridges inside the mouthparts of honeybee workers and drones reflect the caste-related life cycles of honeybees. PMID- 26542140 TI - Erratum, Vol. 12, October 15 Release. AB - [This corrects the article DOI: 10.5888/pcd12.140583.]. In the article "Effectiveness of Fresh to You, a Discount Fresh Fruit and Vegetable Market in Low-Income Neighborhoods, on Children's Fruit and Vegetable Consumption, Rhode Island, 2010-2011," we inadvertently listed an author affiliation for Sara Gorham incorrectly. Ms. Gorham is affiliated with the Institute for Community Health Promotion, Brown University School of Public Health, Providence, Rhode Island. The changes were made to our website on October 16, 2015, and appear online at http://www.cdc.gov/pcd/issues/2015/14_0583.htm. We regret any inconvenience or confusion this error may have caused. PMID- 26542141 TI - Increasing Referrals to a YMCA-Based Diabetes Prevention Program: Effects of Electronic Referral System Modification and Provider Education in Federally Qualified Health Centers. AB - INTRODUCTION: The Diabetes Prevention Program has been translated to community settings with varying success. Although primary care referrals are used for identifying and enrolling eligible patients in the Diabetes Prevention Program, little is known about the effects of strategies to facilitate and sustain eligible patient referrals using electronic health record systems. METHODS: To facilitate and sustain patient referrals, a modification to the electronic health record system was made and combined with provider education in 6 federally qualified health centers in the Bronx, New York. Referral data from April 2012 through November 2014 were analyzed using segmented regression analysis. RESULTS: Patient referrals increased significantly after the modification of the electronic health record system and implementation of the provider education intervention. Before the electronic system modification, 0 to 2 patients were referred per month. During the following year (September 2013 through August 2014), which included the provider education intervention, referrals increased to 1 to 9 per month and continued to increase to 5 to 11 per month from September through November 2014. CONCLUSIONS: Modification of an electronic health record system coupled with a provider education intervention shows promise as a strategy to identify and refer eligible patients to community-based Diabetes Prevention Programs. Further refinement of the electronic system for facilitating referrals and follow-up of eligible patients should be explored. PMID- 26542142 TI - A Pharmacy Student-Facilitated Interprofessional Diabetes Clinic With the Penobscot Nation. AB - BACKGROUND: American Indians/Alaska Natives have a greater increased risk for diabetes than non-Hispanic whites. Lifestyle interventions are effective in preventing and treating diabetes, and an interprofessional approach is important in diabetes management. COMMUNITY CONTEXT: The Penobscot Nation has a health center with a wide range of services. Our goal with the Nation was to 1) establish an interprofessional, student-facilitated diabetes clinic in the health center; 2) assess the clinic's preliminary impact. METHODS: Relationship building and problem solving was instrumental in working toward the first goal. A survey was developed to assess satisfaction with the clinic. The clinical outcomes, mean and median values of HbA1c, were calculated at baseline (spring 2013) and were used to establish 2 groups of patients: those with controlled levels (<7%) and those with uncontrolled levels (>= 7%). HbA1c was reassessed in fall 2013. Changes in HbA1c were calculated and compared using the Wilcoxon signed-rank test. OUTCOMES: The student-facilitated, interprofessional diabetes clinic has operated for 2 years, and changes are under way. More than 90% of participants reported being well satisfied with the clinic in the first year. Among the group with uncontrolled HbA1c (n = 18), mean HbA1c values declined from 9.3% to 7.6% (P = .004). Among the group with controlled HbA1c (n = 30), 83% were controlled at follow-up. INTERPRETATION: The Penobscot diabetes clinic is evolving to meet the needs of community members, and pharmacy students have an interprofessional practice site well suited for experiential learning. PMID- 26542143 TI - The Dose-Response Relationship Between Tobacco Education Advertising and Calls to Quitlines in the United States, March-June, 2012. AB - INTRODUCTION: We estimated changes in call volume in the United States in response to increases in advertising doses of the Tips From Former Smokers (Tips) campaign, the first federal national tobacco education campaign, which aired for 12 weeks from March 19 to June 10, 2012. We also measured the effectiveness of ad taglines that promoted calls directly with a quitline number (1-800-QUIT-NOW) and indirectly with a cessation help website (Smokefree.gov). METHODS: Multivariate regressions estimated the weekly number of calls to 1-800-QUIT-NOW by area code as a function of weekly market-level gross rating points (GRPs) from CDC's Tips campaign in 2012. The number of quitline calls attributable solely to Tips was predicted. RESULTS: For quitline-tagged ads, an additional 100 television GRPs per week was associated with an increase of 89 calls per week in a typical area code in the United States (P < .001). The same unit increase in advertising GRPs for ads tagged with Smokefree.gov was associated with an increase of 29 calls per week in any given area code (P < .001). We estimated that the Tips campaign was responsible for more than 170,000 additional calls to 1-800-QUIT-NOW during the campaign and that it would have generated approximately 140,000 additional calls if all ads were tagged with 1-800-QUIT-NOW. CONCLUSION: For campaign planners, these results make it possible to estimate 1) the likely impact of tobacco prevention media buys and 2) the additional quitline capacity needed at the national level should future campaigns of similar scale use 1-800-QUIT-NOW taglines exclusively. PMID- 26542144 TI - Selected Diagnosed Chronic Conditions by Sexual Orientation: A National Study of US Adults, 2013. AB - INTRODUCTION: Research is needed on chronic health conditions among lesbian, gay, and bisexual populations. The objective of this study was to examine 10 diagnosed chronic conditions, and multiple (>=2) chronic conditions (MCC), by sexual orientation among US adults. METHODS: The 2013 National Health Interview Survey was used to generate age-adjusted prevalence rates and adjusted odds ratios of diagnosed chronic conditions and MCC for civilian, noninstitutionalized US adults who identified as gay/lesbian, straight, or bisexual, and separately for men and women. Chronic conditions were selected for this study on the basis of previous research. RESULTS: Hypertension and arthritis were the most prevalent conditions for all groups. Gay/lesbian adults had a 4.7 percentage-point higher prevalence of cancer than bisexual adults, and a 5.6 percentage-point higher prevalence of arthritis and a 2.9 percentage point higher prevalence of hepatitis than straight adults. The prevalence of chronic obstructive pulmonary disease was 8.1 percentage points higher among bisexual adults than among gay/lesbian adults and 7.0 percentage points higher than among straight adults. These differences remained in the multivariate analyses. Additional differences were found in the sex-stratified analyses. No significant differences were found in MCC by sexual orientation. CONCLUSION: After age adjustment and controlling for sociodemographic characteristics, only a few significant health disparities for diagnosed chronic conditions were found by sexual orientation, and none for MCC. However, for conditions where differences were found, magnitudes were relatively large. Further examination of these differences among gay/lesbian and bisexual adults could yield a better understanding of why these disparities exist. PMID- 26542145 TI - Mechanisms of fibroblast growth factor signaling in the ovarian follicle. AB - Fibroblast growth factors (FGFs) have been shown to alter growth and differentiation of reproductive tissues in a variety of species. Within the female reproductive tract, the effects of FGFs have been focused on the ovary, and the most studied one is FGF2, which stimulates granulosa cell proliferation and decreases differentiation (decreased steroidogenesis). Other FGFs have also been implicated in ovarian function, and this review summarizes the effects of members of two subfamilies on ovarian function; the FGF7 subfamily that also contains FGF10, and the FGF8 subfamily that also contains FGF18. There are data to suggest that FGF8 and FGF18 have distinct actions on granulosa cells, despite their apparent similar receptor binding properties. Studies of non-reproductive developmental biology also indicate that FGF8 is distinct from FGF18, and that FGF7 is also distinct from FGF10 despite similar receptor binding properties. In this review, the potential mechanisms of differential action of FGF7/FGF10 and FGF8/FGF18 during organogenesis will be reviewed and placed in the context of follicle development. A model is proposed in which FGF8 and FGF18 differentially activate receptors depending on the properties of the extracellular matrix in the follicle. PMID- 26542146 TI - Surviving Mass Extinctions through Biomineralized DNA. AB - Even in the worst of conditions, such as those which occurred during mass extinction events, life on Earth never totally stopped. Aggressive chemical and physical attacks able to sterilize or poison living organisms occurred repeatedly. Surprisingly, DNA was not degraded, denatured or modified to the point of losing the capability of transferring the genetic information to the next generations. After the events of mass extinction life was able to survive and thrive. DNA was passed on despite being an extremely fragile biomolecule. The potential implications of hydroxyapatite protection of DNA are discussed in this Concept article including how DNA acts as a template for hydroxyapatite (HAp) formation, how cell death can trigger biomineralization, and how DNA can be successfully released from HAp when the conditions are favorable for life. PMID- 26542147 TI - Hand-foot syndrome following decitabine. PMID- 26542148 TI - Paraneoplastic cerebellar degeneration as an early sign of classical Hodgkin lymphoma. PMID- 26542151 TI - [The place of pediatricians in newborn screening]. AB - Newborn screening was implemented in France 40 years ago, initiated by a small group of pediatricians and biologists. Pediatricians play a central role in this action, from the reflection on new prospects to the care of affected children. This article reviews all the steps in newborn screening where pediatricians play a role as well as recent and future changes. PMID- 26542149 TI - The Role of 3-O-Sulfogalactosylceramide, Sulfatide, in the Lateral Organization of Myelin Membrane. AB - Sulfatide (3-O-sulfogalactosylceramide, SM4s) was isolated by Thudichum from the human brain in 1884. Together with galactosylceramide, its direct metabolic precursor in the biosynthetic pathway, sulfatide is highly enriched in myelin in the central and peripheral nervous system, and it has been implicated in several aspects of the biology of myelin-forming cells. Studies obtained using galactolipid-deficient mice strongly support the notion that sulfatide plays critical roles in the correct structure and function of myelin membrane. A number of papers are suggesting that these roles are mediated by a specific function of sulfatide in the lateral organization of myelin membrane, thus affecting the sorting, lateral assembly, membrane dynamics and also the function of specific myelin proteins in different substructures of the myelin sheath. The consequences of altered sulfatide metabolism and sulfatide-mediated myelin organization with respect to myelin diseases are still poorly understood, but it's very likely that sulfatide might represent not only a critical player in the pathogenesis of several diseases, including multiple sclerosis and Alzheimer's disease, but also a potentially promising therapeutic target. PMID- 26542150 TI - Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability. AB - Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated. PMID- 26542152 TI - Development and evaluation of ultra-small nanostructured lipid carriers: novel topical delivery system for athlete's foot. AB - Athlete's foot is a fungal infection of the foot which causes dry, itchy, flaky condition of the skin caused by Trichophyton species. In this study, the potential of ultra-small nanostructured lipid carrier (usNLC)-based topical gel of miconazole nitrate for the treatment of athlete's foot was evaluated. Nanostructure lipid carriers (NLCs) prepared by melt emulsification and sonication technique were characterized for particle size, drug entrapment, zeta potential and drug release. The optimized usNLC revealed particle size 53.79 nm, entrapment efficiency 86.77%, zeta potential -12.9 mV and polydispersity index (PDI) of 0.27. The drug release studies of usNLC showed initial fast release followed by sustained release with 91.99% drug released in 24 h. Optimized usNLCs were incorporated into carbopol-934 gel and evaluated for pH (6.8), viscosity (36,400 mPa s) and texture analysis. Antifungal activity against Trichophyton mentagrophytes exhibited wider zone of inhibition, 6.6 +/- 1.5 mm for optimized usNLC3 gel viz-a-viz marketed gel formulation (3.7 +/- 1.2 mm). Hen's egg test chorioallantoic membrane (HET-CAM) irritation test confirmed optimized usNLC gel to be non-irritant to chorioallantoic membrane. Improved dermal delivery of miconazole by usNLC gel could be achieved for treatment of athlete's foot. PMID- 26542153 TI - Beneficial Effects of Improvement in Depression, Pain Catastrophizing, and Anxiety on Pain Outcomes: A 12-Month Longitudinal Analysis. AB - Depression, pain catastrophizing, and anxiety commonly co-occur with chronic pain. However, the degree to which improvement in these psychological comorbidities predicts subsequent pain outcomes and, in particular, the relative effects of these 3 psychological factors with respect to each other is only partially known. Longitudinal analysis of 250 primary care patients with chronic musculoskeletal pain enrolled in the Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial was examined, using data gathered at baseline, and at 3 and 12 months. Mixed effects model repeated measures analyses were used to determine if changes in depression, pain catastrophizing, and anxiety predicted a subsequent reduction in pain intensity or interference and pain-related disability. Defining a clinically significant change as twice the standard error of measurement for each predictor, we found that a 2-standard error of measurement improvement in depression, pain catastrophizing, and anxiety resulted in, respectively, an effect size decrease in pain intensity or interference of .45, .33, and .12; a 14%, 12%, and 6% reduction in the number of pain-specific disability days; and a 43%, 30%, and 28% decreased likelihood of high disability (defined as >=10 pain-specific disability days in the past 4 weeks). In summary, improvements in 3 common psychological comorbidities predicted better pain outcomes. PERSPECTIVE: Because depression, pain catastrophizing, and anxiety commonly accompany chronic pain and might adversely affect pain outcomes, treatment of these modifiable psychological factors is warranted to optimize the effectiveness of pain-specific therapies. PMID- 26542154 TI - [Concept of budget-based remuneration system for the fields of psychiatry and psychotherapy, psychosomatic medicine and psychotherapy, child and adolescent psychiatry and psychotherapy]. AB - A new remuneration system is currently being developed for the hospital care of people with mental disorders. Last year, because of sharp criticism the option phase of the planned Flat-rate Charges in Psychiatry and Psychosomatics (Pauschalierende Entgelte Psychiatrie und Psychosomatik, PEPP) was extended by 2 years. During this time the Federal Ministry of Health wants to look for alternatives and possible starting points for the further development of care. Now, 16 scientific professional associations and organisations have presented a joint concept for a sustainable solution: the budget-based remuneration system. The system is suitable for ensuring that people with mental disorders are treated according to their particular needs and for promoting the appropriate further development of regional care in all treatment settings. It corresponds with the objectives as formulated in Section 17d of the Hospital Finance Act (Krankenhausfinanzierungsgesetz, KHG) and translates the PEPP system, which is currently being developed and focusses on average prices, into a performance oriented, transparent budgetary system. The fundamental principle is the separation of the individual hospitals' budgeting on the basis of evidence-based, feature- and performance-related modules and billing in the form of advance payments from the agreed budget. PMID- 26542155 TI - [Should antipsychotics be used in prodromal stages of schizophrenia to prevent psychosis? Pro]. PMID- 26542156 TI - [Should antipsychotics be used in prodromal stages of schizophrenia to prevent psychosis? Con]. PMID- 26542157 TI - [Trauma-focused psychotherapy: Technique, area of application, and treatment outcome]. AB - Traumatic events may lead to trauma-related disorders such as the posttraumatic stress disorder (PTSD) and constraints in quality of life. Meanwhile, there are different trauma-focused psychotherapies that aim to prevent PTSD shortly after experiencing a traumatic event and interventions that aim to treat PTSD. In Germany, cognitive-behavioral and psychodynamic trauma-focused approaches are commonly applied. While cognitive-behavioral programs aim at early exposure with the traumatic event, psychodynamic approaches emphasize the need of a period of stabilization before undergoing exposure. With regard to empirical evidence, cognitive-behavioral programs were able to prove their efficacy most often and are recommended in national and international guidelines. The German S3 guideline PTSD is currently under revision. PMID- 26542160 TI - Direct medical costs attributable to type 2 diabetes mellitus: a population-based study in Catalonia, Spain. AB - We estimated healthcare costs associated with patients with type 2 diabetes compared with non-diabetic subjects in a population-based primary care database through a retrospective analysis of economic impact during 2011, including 126,811 patients with type 2 diabetes in Catalonia, Spain. Total annual costs included primary care visits, hospitalizations, referrals, diagnostic tests, self monitoring test strips, medication, and dialysis. For each patient, one control matched for age, gender and managing physician was randomly selected from a population database. The annual average cost per patient was ?3110.1 and ?1803.6 for diabetic and non-diabetic subjects, respectively (difference ?1306.6; i.e., 72.4 % increased cost). The costs of hospitalizations were ?1303.1 and ?801.6 (62.0 % increase), and medication costs were ?925.0 and ?489.2 (89.1 % increase) in diabetic and non-diabetic subjects, respectively. In type 2 diabetic patients, hospitalizations and medications had the greatest impact on the overall cost (41.9 and 29.7 %, respectively), generating approximately 70 % of the difference between diabetic and non-diabetic subjects. Patients with poor glycaemic control (glycated haemoglobin >7 %; >53 mmol/mol) had average costs of ?3296.5 versus ?2848.5 for patients with good control. In the absence of macrovascular complications, average costs were ?3008.1 for diabetic and ?1612.4 for non diabetic subjects, while its presence increased costs to ?4814.6 and ?3306.8, respectively. In conclusion, the estimated higher costs for type 2 diabetes patients compared with non-diabetic subjects are due mainly to hospitalizations and medications, and are higher among diabetic patients with poor glycaemic control and macrovascular complications. PMID- 26542161 TI - Effect of First Ray Insufficiency and Metatarsal Index on Metatarsalgia in Hallux Valgus. AB - BACKGROUND: Two concepts have been proposed to explain the etiology of metatarsalgia in hallux valgus patients: First, as the magnitude of hallux valgus increases, there is a mechanical overload of the lesser metatarsals. Second, increased relative lesser metatarsal length is a factor in the development of metatarsalgia. However, there is no current evidence that these structural factors lead to primary metatarsalgia. The purpose of the study was to evaluate the factors associated with metatarsalgia in hallux valgus patients. METHODS: A cross-sectional study of 121 consecutive adult patients with non-arthritic hallux valgus was carried out. Binary logistic regression was performed to identify the effect of the clinical and demographic factors on the occurrence of metatarsalgia. One hundred twenty-one patients (184 feet) with hallux valgus were analyzed. The median weight was 65 kg (interquartile range 58-72). RESULTS: Metatarsalgia was present in 84 (45.6%) feet. The binary logistic regression showed that lesser toe deformity (OR 2.6, 95% CI 0.2-0.5), gastrocnemius shortening (OR 5.8, 95% CI 2.8-12.3), metatarsal index (OR 0.3, 95% CI 0.2-0.5), and weight (OR 2.5, 95% CI 1.2-5.3) were significantly associated. CONCLUSION: Metatarsalgia occurs in almost half of hallux valgus patients. It has a multifactorial etiology. Our findings contradict the common theory that both the magnitude of hallux valgus deformity and an increased length of the lesser metatarsals, by themselves, lead to primary metatarsalgia. Metatarsalgia was associated with Achilles shortening, excessive weight, and associated lesser toe deformity. These factors should be addressed in order to treat this disorder adequately. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 26542162 TI - Effect of Obesity on Clinical and Radiographic Outcomes Following Reconstruction of Stage II Adult Acquired Flatfoot Deformity. AB - BACKGROUND: Obesity is a known risk factor for the development of adult acquired flatfoot deformity (AAFD), but obesity's effects on outcomes following AAFD reconstruction are unknown. We hypothesized that obesity would negatively impact outcomes following joint-preserving stage II AAFD reconstruction. METHODS: This retrospective study compared the outcomes of normal-weight (18.5 kg/m(2) <= BMI < 25 kg/m(2)), overweight (25 kg/m(2) <= BMI < 30 kg/m(2)), and obese (BMI >= 30 kg/m(2)) patients after AAFD reconstruction. Clinical outcome measures included the Foot and Ankle Outcome Score (FAOS), Short-Form 12 (SF-12), and Numeric Rating Scale of Pain (NRS Pain) administered preoperatively and at least 1 year postoperatively. Anteroposterior and lateral radiographs were taken preoperatively and at least 6 months postoperatively. Pre- to postoperative changes in outcome measures were assessed within BMI classes. Preoperative, postoperative, and pre- to postoperative changes in outcomes were compared among BMI classes. There were 41 normal-weight patients, 39 overweight patients, and 44 obese patients with a mean age of 56 years, FAOS follow-up of 2.9 years, and radiographic follow-up of 2.1 years. Demographics and reconstructive procedures were comparable among the 3 BMI classes. RESULTS: All outcomes significantly increased pre- to postoperatively in the 3 groups with the exception of the FAOS Symptoms subscale for normal-weight patients (P = .340) and SF-12 Mental Component score for all 3 BMI classes (P > .999). Preoperatively, obese patients had more symptoms than normal-weight patients, scoring 12 points lower on the FAOS Symptoms subscore (P = .008). Obese patients also scored 11 points lower preoperatively on the SF-12 Overall score (P = .028) and had 31% greater pain than normal-weight patients (P = .003). There were no differences among the 3 BMI classes in any postoperative outcomes assessed. CONCLUSION: Although obese patients had significantly worse symptoms, overall health, and NRS pain scores preoperatively, the short-term clinical and radiographic outcomes of stage II AAFD reconstruction were similar for normal-weight, overweight, and obese patients. We suggest that joint-preserving reconstruction remains a viable alternative to fusion of the triple joint complex for the treatment of overweight and obese stage II AAFD patients. LEVEL OF EVIDENCE: Level III, retrospective cohort study. PMID- 26542163 TI - Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis. AB - BACKGROUND AND OBJECTIVES: Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 46 patients with AAV diagnosed between January 1990 and December 2011 at the Nephrology Unit of Parma University Hospital; 30 of them had undergone renal biopsy. We analyzed serum levels of C3 (sC3) and C4 (sC4) and, for 19 patients who had frozen plasma, plasma Bb and C5b-9 levels. We also reviewed all kidney biopsy specimens, specifically searching for histologic signs of TMA, and performed immunofluorescence or immunohistochemistry for C3d, C4d, Bb and C5b-9. RESULTS: sC3 was below the lower limit of normal in 35% of the patients, whereas C4 was low in only 2%. Patients with low sC3 tended to be older (P=0.04) and to have lower eGFR at diagnosis (P=0.06). The median follow-up was 78 months (interquartile range, 18-135 months); 18 patients reached ESRD (10 of 14 and 8 of 26 in the low and normal sC3 groups, respectively). Death-censored renal survival was lower in the low sC3 group than in the normal sC3 group (log-rank test, P=0.01). Eight of the 30 patients who had undergone biopsy (27%) had histologic signs of TMA; these signs were more frequent in patients with low sC3 (5 of 10 versus 3 of 20; P=0.04). Notably, patients with histologic signs of TMA had a dramatically worse death-censored renal survival than patients without TMA (log rank test, P=0.01), with ESRD occurring in 8 of 8 patients with TMA versus 8 of 22 patients without TMA. CONCLUSIONS: Low sC3 levels and histologic signs of TMA are associated with a poor renal prognosis in patients with AAV. PMID- 26542164 TI - Sex Differences in Landing Biomechanics and Postural Stability During Adolescence: A Systematic Review with Meta-Analyses. AB - BACKGROUND: The adolescent 'growth spurt' results in rapid growth of the skeletal system. It has been theorised that absence of a concomitant increase in muscular adaptations in female athletes may predispose them to an increased risk of anterior cruciate ligament injuries. OBJECTIVES: To determine if sex differences exist in landing biomechanics and postural stability of adolescent athletes; with a further objective of determining if such differences are propagated during adolescence. DATA SOURCES: The following databases were searched: MEDLINE, EMBASE, CINAHL, PEDro, PubMed, SPORTDiscus and Web of Science. Research papers were identified by including search terms for neuromuscular control, lower limb and pubertal development. INCLUSION CRITERIA: Studies were required to be written in English; report on biomechanical analyses; include landing or postural control tasks; be cross-sectional or longitudinal; and include healthy adolescent/pubertal subjects. STUDY APPRAISAL AND SYNTHESIS METHODS: A modified version of the Strengthening the Reporting of Observational studies in Epidemiology checklist was used to rate methodological quality. Meta-analyses were performed when more than one study reported on an outcome measure. RESULTS: Sixteen articles were included. The overall methodological quality of evaluated studies was low (mean score = 5.75/10 points). Adolescent females exhibited increased knee valgus with increasing maturity. There was no consensus on sex differences in postural stability. CONCLUSIONS: With increasing maturation, females are characterized by increased knee valgus during landing tasks. To date, no research has longitudinally investigated postural stability development during adolescence in females, despite the importance of postural control training in injury prevention programmes. Therefore, further research on this topic is warranted. PMID- 26542165 TI - Intra-bolus pressure and esophagogastric gradient, assessed with high-resolution manometry, are associated with acid exposure and proximal migration of refluxate. AB - Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 +/- 1.6 mmHg) respect to NERD patients (8.9 +/- 2.8 mmHg) and HVs (9.2 +/- 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 +/- 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 +/- 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation. PMID- 26542166 TI - The survival of direct composite restorations in the management of severe tooth wear including attrition and erosion: A prospective 8-year study. AB - OBJECTIVES: Survival of directly placed composite to restore worn teeth has been reported in studies with small sample sizes, short observation periods and different materials. This study aimed to estimate survival for a hybrid composite placed by one clinician up to 8-years follow-up. METHODS: All patients were referred and recruited for a prospective observational cohort study. One composite was used: Spectrum((r)) (DentsplyDeTrey). Most restorations were placed on the maxillary anterior teeth using a Dahl approach. RESULTS: A total of 1010 direct composites were placed in 164 patients. Mean follow-up time was 33.8 months (s.d. 27.7). 71 of 1010 restorations failed during follow-up. The estimated failure rate in the first year was 5.4% (95% CI 3.7-7.0%). Time to failure was significantly greater in older subjects (p=0.005) and when a lack of posterior support was present (p=0.003). Bruxism and an increase in the occlusal vertical dimension were not associated with failure. The proportion of failures was greater in patients with a Class 3 or edge-to-edge incisal relationship than in Class 1 and Class 2 cases but this was not statistically significant. More failures occurred in the lower arch (9.6%) compared to the upper arch (6%) with the largest number of composites having been placed on the maxillary incisors (n=519). CONCLUSION: The worn dentition presents a restorative challenge but composite is an appropriate restorative material. CLINICAL SIGNIFICANCE: This study shows that posterior occlusal support is necessary to optimise survival. PMID- 26542167 TI - Fascia compared to one-piece composite cartilage-perichondrium grafting for tympanoplasty. AB - OBJECTIVE: To evaluate the effectiveness of type 1 tympanoplasty with one-piece composite cartilage-perichondrium (CCP) grafts compared to temporalis fascia (TF) grafts for tympanic membrane (TM) closure and hearing improvement in adult patients with a subtotal TM perforation and chronic otitis media (COM). DATA SOURCES: PubMed, Embase, Cochrane Library. REVIEW METHODS: A systematic search was conducted. Relevance and validity of selected articles were assessed. Studies that scored moderate or high on relevance were included, and relevant data for both outcomes were extracted. For the outcome of TM closure, absolute risk differences (RD), relative risks, and number needed to treat with their respective 95% confidence intervals were calculated when possible. RESULTS: We retrieved 3,783 unique studies. Ten studies satisfied the eligibility criteria. Four studies of moderate validity showed RD ranging from 0.08 to 0.13 in favor of the CCP graft compared to the TF graft for TM closure 1 year or more postoperatively, but this was not statistically significant. Five studies of moderate to high validity showed no clinically relevant difference in hearing improvement between both intervention groups at a minimum follow-up of 3 months. The relative air-bone gap closure ranged from 5.7 to 11.5 dB in the TF group and from 8.9 to 12.7 dB in the CCP group. CONCLUSIONS: There is no evidence of superiority of one-piece CCP grafting over TF grafting in type 1 tympanoplasty regarding complete closure of a subtotal perforated TM 1 year or more postoperatively or hearing improvement at a minimum of 3 months follow-up. Laryngoscope, 126:1662-1670, 2016. PMID- 26542168 TI - Inactivation of Bombyx mori macula-like virus under physical conditions. AB - The Bombyx mori macula-like virus (BmMLV) is a member of the genus Maculavirus, family Tymoviridae, and contains a positive-sense single-stranded RNA genome. Previously, we reported that almost all B. mori-derived cell lines have already been contaminated with BmMLV via an unknown infection route. Since B. mori derived cell lines are used for the baculovirus expression vector system, the invasion of BmMLV will cause a serious safety risk in the production of recombinant proteins. In this study, to determine the inactivation effectiveness of BmMLV, viruses were treated with various temperatures as well as gamma and ultraviolet (UV) light radiation. After these treatments, the virus solutions were inoculated into BmMLV-free BmVF cells. At 7 days postinoculation, the amount of virus in cells was evaluated by real-time reverse transcription PCR. Regarding heat treatment, conditions under 56 degrees C for 3 h were tolerated, whereas infectivity disappeared after treatment at 75 degrees C for 1 h. Regarding gamma radiation treatment, viruses were relatively stable at 1 kGy; however, their infectivity was entirely eliminated at a dose of 10 kGy. With 254 nm UV-C treatment, viruses were still active at less than 120 mJ/cm(2); however, their infectivity was completely lost at greater than 140 mJ/cm(2) UV-C radiation. These results provide quantitative evidence of the potential for BmMLV inactivation under a variety of physical conditions. PMID- 26542169 TI - The function and interrelationship between GDF5 and ERG-010 during chondrogenesis in vitro. AB - Joint formation begins with the establishment of an interzone within the cartilaginous anlagen of the future skeleton. Both GDF5 and ERG are proposed as regulators of chondrocyte differentiation during and post interzone formation. The aim of this study was to examine the relationship between Gdf5 and Erg expression and downstream effects on chondrocyte gene expression. Erg expression was identified in mouse knee joints at E13.5. Expression analyses were performed using micromass cultures of murine C3H10T1/2 mesenchymal cells undergoing induced chondrogenesis in the presence and absence of GDF5 and ERG. At E13.5, Erg expression was found to surround epiphyseal chondrocytes and span the interzone up to the intermediate zone. Erg splice forms were expressed in micromass cultures, and their expression profile was altered by the addition of recombinant GDF5 depending on the stage of differentiation. Overexpression of Erg-010 resulted in a downregulation of Col2a1 and Col10a1. Microarray analysis following Erg-010 overexpression identified two potential downstream targets, Ube2b and Osr2, which were also differentially regulated by GDF5. Erg regulation by GDF5 in induced mesenchymal cells in vitro is dependent on the stage of chondrogenesis, and its expression in vivo demarcates chondrocytes that are not destined to be consumed by endochondral ossification. Functionally, Erg expression causes downregulation of Col2a1 and Col10a1 expression and this effect is potentially mediated by Osr2 and/or Ube2b. Combined, these data suggest a possible pathway linking GDF5, ERG and downstream factors in the processes of chondrocyte differentiation during articular joint formation. PMID- 26542170 TI - Scaffold-free and scaffold-assisted 3D culture enhances differentiation of bone marrow stromal cells. AB - 3D cultures of stem cells can preserve differentiation potential or increase the efficiency of methods that induce differentiation. Mouse bone marrow-derived stromal cells (BMSCs) were cultured in 3D as scaffold-free spheroids or "mesoid bodies" (MBs) and as aggregates on poly(lactic) acid microspheres (MB/MS). 3D cultures demonstrated viable cells, interaction on multiple planes, altered cell morphology, and the formation of structures similar to epithelial cell bridges. Cell proliferation was limited in suspension cultures of MB and MB/MS; however, cells regained proliferative capacity when transferred to flat substrates of tissue culture plates (TCPs). Expanded as monolayer, cells retained expression of Sca-1 and CD44 stem cell markers. 3D cultures demonstrated enhanced potential for adipogenic and osteogenic differentiation showing higher triglyceride accumulation and robust mineralization in comparison with TCP cultures. Enhanced and efficient adipogenesis was also observed in 3D cultures generated in a rotating cell culture system. Preservation of multilineage potential of BMSC was demonstrated in 5-azacytidine treatment of 3D cultures and TCP by expression of cardiac markers GATA4 and ACTA1 although functioning cardiomyocytes were not derived. PMID- 26542172 TI - Development and Validation of an Expanded Version of the Three-Factor Levenson Self-Report Psychopathy Scale. AB - The Levenson Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995 ) is a brief self-report questionnaire frequently used in psychopathy research. Although the scale has many desirable properties such as brevity and being available in the public domain, there are also several psychometric concerns associated with it, including low internal consistency, problematic construct validity, and incomplete conceptual coverage of several components of psychopathy. In 2 studies, we provide evidence that additional items can augment the LSRP to address the aforementioned concerns. In the first study, using a large sample of students and members of the general Australian community (n = 729), we found that an expanded 36-item, 3-factor version of the LSRP was associated with improvements in internal consistency and construct coverage with little degradation in model fit. In the second study, using another Australian community sample (n = 300), we replicated the results of Study 1 and demonstrated improvements in construct validity for the expanded 36-item, 3-factor scale compared to the 19-item, 3-factor scale. Our results indicate that, although slightly longer, the expanded version of the 3-factor LSRP ameliorates many of the concerns associated with its original counterpart. PMID- 26542171 TI - Calmodulin kinase II inhibitor regulates calcium homeostasis changes caused by acute beta-adrenergic receptor agonist stimulation in mouse ventricular myocytes. AB - Ca(2+)/calmodulin-dependent kinase II (CaMKII) is an important regulatory molecule under chronic beta-adrenergic receptor agonist stimulation but cardiac diseases also occur when beta-adrenergic elevated acutely in the circulation, of which the most harmful is lethal arrhythmia. The purpose of this study was to explore the effects of acute isoproterenol (ISO) stimulation on intracellular calcium handling and evaluate whether CaMKII inhibitor may change the effects caused by isoproterenol. Mouse ventricular myocytes were acutely isolated by enzymatic method and divided into four groups: control group, ISO group, KN-93 group, ISO + KN-93 group. The whole-cell patch clamp was used to study the effect of ISO and KN-93 on L-type calcium current (IL-Ca) in isolated ventricular myocytes. The technology of laser scanning confocal microscopy was used to record cardiomyocyte calcium transients after ISO and KN-93 were used. ISO significantly increased current density of IL-Ca (p < 0.01) and decreased the half activation voltage (p < 0.01), half inactivation voltage (p < 0.01), and the recovery time constant (p < 0.01). In the presence of CaMKII inhibitor, KN-93 decreased the increased current density of IL-Ca (p < 0.05), increased the reduced half activation voltage caused by ISO (p < 0.01), and prolonged the shortened recovery time constant caused by ISO (p < 0.01). In addition, KN-93 alone can change the activation, inactivation, and recovery kinetics of L-type calcium channels. Moreover, ISO significantly increased the Ca(2+) transient amplitude during both stimulation frequencies (0.5 Hz: p < 0.01, 1 Hz: p < 0.01) and was easy to induce calcium disorders; in the presence of KN-93, these changes were weakened (0.5 Hz: p < 0.05, 1 Hz: p < 0.05). Therefore, changes of the calcium homeostasis in cardiomyocytes caused by ISO can be adjusted by KN-93, thus KN-93 plays a vital role in regulating calcium homeostasis changes caused by ISO. PMID- 26542174 TI - Pregnancy in Women With Structural Heart Disease: Experience in a Centre. PMID- 26542173 TI - ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6. AB - RNA binding proteins (RBPs)-mediated post-transcriptional control has been implicated in influencing various aspects of RNA metabolism and playing important roles in mammalian development and pathological diseases. However, the functions of specific RBPs and the molecular mechanisms through which they act in monocyte/macrophage differentiation remain to be determined. In this study, through bioinformatics analysis and experimental validation, we identify that ZFP36L1, a member of ZFP36 zinc finger protein family, exhibits significant decrease in acute myeloid leukemia (AML) patients compared with normal controls and remarkable time-course increase during monocyte/macrophage differentiation of PMA-induced THP-1 and HL-60 cells as well as induction culture of CD34(+) hematopoietic stem/progenitor cells (HSPCs). Lentivirus-mediated gain and loss of function assays demonstrate that ZFP36L1 acts as a positive regulator to participate in monocyte/macrophage differentiation. Mechanistic investigation further reveals that ZFP36L1 binds to the CDK6 mRNA 3'untranslated region bearing adenine-uridine rich elements and negatively regulates the expression of CDK6 which is subsequently demonstrated to impede the in vitro monocyte/macrophage differentiation of CD34(+) HSPCs. Collectively, our work unravels a ZFP36L1 mediated regulatory circuit through repressing CDK6 expression during monocyte/macrophage differentiation, which may also provide a therapeutic target for AML therapy. PMID- 26542175 TI - Conduction Abnormalities and Pacemaker Implantations After SAPIEN 3 Vs SAPIEN XT Prosthesis Aortic Valve Implantation. AB - INTRODUCTION AND OBJECTIVES: Transcatheter aortic valve implantation is increasingly used in patients with aortic stenosis. Post-procedural intraventricular conduction abnormalities and permanent pacemaker implantations remain a serious concern. Recently, the Edwards SAPIEN 3 prosthesis has replaced the SAPIEN XT. We sought to determine the incidences of new-onset intraventricular conduction abnormalities and permanent pacemaker implantations by comparing the 2 devices. METHODS: We analyzed the last consecutive 103 patients undergoing transcatheter aortic valve implantation with SAPIEN XT before SAPIEN 3 was used in the next 105 patients. To analyze permanent pacemaker implantations and new-onset intraventricular conduction abnormalities, patients with these conditions at baseline were excluded. Electrocardiograms were recorded at baseline, after the procedure, and before discharge. RESULTS: SAPIEN 3 was associated with higher device success (100% vs 92%; P=.005) and less paravalvular leakage (0% vs 7%; P<.001). The incidence of permanent pacemaker implantations was 12.6% (23 of 183) with no difference between the 2 groups (SAPIEN 3: 12.5% [12 of 96] vs SAPIEN XT: 12.6% [11 of 87]; P=.99). SAPIEN 3 was associated with a higher rate of new-onset intraventricular conduction abnormalities (49% vs 27%; P=.007) due to a higher rate of fascicular blocks (17% vs 5%; P=.021). There was no statistically significant difference in transient (29% [20 of 69] vs persistent 19% [12 of 64]; P=.168) left bundle branch blocks (28% [19 of 69] vs 17% [11 of 64]; P=.154) when SAPIEN 3 was compared with SAPIEN XT. CONCLUSIONS: We found a trend toward a higher rate of new-onset intraventricular conduction abnormalities with SAPIEN 3 compared with SAPIEN XT, although this did not result in a higher permanent pacemaker implantation rate. PMID- 26542176 TI - Endostatin exerts radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression. AB - BACKGROUND: To determine the effects of endostatin on vascular growth factor receptor 2 (VEGFR2) expression in non-small cell lung cancer (NSCLC) cells and the mechanisms underlying its radiosensitizing effect. METHODS: VEGFR2 mRNA levels were determined in different NSCLC cell lines using qRT-PCR. RT-PCR and Western blot assays were used to assess the expression of mRNA and proteins. The radiosensitivity of the cells was determined by colony-formation assays; and cell apoptosis and cell cycle distribution were determined by flow cytometry. RESULTS: VEGFR2 mRNA levels differed among the five NSCLC cell lines (P < 0.01), with the highest expression in Calu-1 cells and lowest in A549 cells. Endostatin significantly inhibited the growth of Calu-1 cells (P < 0.01) (IC20 = 296.5 MUg/ml), and the expression of VEGFR2 and HIF-1alpha (P < 0.05). Phosphorylation of protein kinase B (Akt), extracellular signal-regulated kinases 1/2 (ERK1/2), and p38 were significantly lower in endostatin-treated cells than control (P < 0.05). Endostatin enhanced the radiosensitivity of Calu-1 cells to SER = 1.38 and induced apoptosis (P < 0.01) and G2/M blockage (P < 0.01). However, endostatin had limited effects on A549 cells. Compared with Calu-1 cells, there was not significantly effects on cell radiosensitivity (SER = 1.09). CONCLUSIONS: Endostatin induces apoptosis and enhances radiosensitivity of the VEGFR2 high expressing cell line Calu-1, but it has a limited effect on the VEGFR2 low expressing cell line A549. PMID- 26542177 TI - GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status. AB - PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG. PMID- 26542178 TI - Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer. AB - INTRODUCTION: Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I. PATIENTS AND METHODS: ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by real-time quantitative RT-PCR in fresh frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLC patients. Later, significant association between gene expression levels, clinicopathological characteristics and patient's disease-free survival was assessed. RESULTS: We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease free survival in stage I NSCLC patients. CONCLUSION: Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLC patients. PMID- 26542180 TI - Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of regenerative medicine. PMID- 26542179 TI - The clinical phenotype of YWHAE-NUTM2B/E positive pediatric clear cell sarcoma of the kidney. AB - Clear cell sarcoma of the kidney (CCSK) although uncommon, is the second most frequent renal malignancy of childhood. Until now, the sole recurrent genetic aberration identified in CCSKs is t(10;17)(q22;p13), which gives rise to a fusion transcript of YWHAE and NUTM2B/E. So far, the clinical relevance of this fusion transcript is unknown. The aim of this descriptive study was to determine the clinical phenotype of t(10;17)(q22;p13) positive CCSKs. Snap-frozen tissues, formalin-fixed paraffin-embedded tissues or RNA previously extracted from CCSK samples throughout European, North-American and Japanese study groups were screened by RT-PCR for the YWHAE-NUTM2B/E transcript. Clinical characteristics, tumor characteristics, and outcome of patients with and without the fusion transcript were studied. The cohort comprised 51 previously published cases to which were added 139 internationally collected CCSK samples. RNA from 57 of these additionally collected cases was of sufficient quality to be successfully screened for the YWHAE-NUTM2B/E transcript. In total, seven of the 108 cases harbored the fusion transcript. Patients with tumors containing the fusion transcript were relatively young (median age 10 months), had associated low median tumor volumes and stage I disease was not observed in these patients. Two of seven patients relapsed and one of seven patients died of disease. Ranges of values were not overtly different between patients with and without the fusion transcript; however, the number of fusion transcript positive cases turned out to be too small to permit reliable statistical analysis. The current study did not identify an explicit clinical phenotype of CCSK cases harboring the YWHAE NUTM2B/E fusion transcript. PMID- 26542181 TI - Difference in vacuum-formed mouthguard thickness according to timing of vacuum application. AB - AIM: The purpose of this study was to examine the differences of the vacuum formed mouthguard thickness by the timing of vacuum application. MATERIALS AND METHODS: The material used in this study was a mouthguard sheet of 3.8-mm ethylene vinyl acetate. Three conditions of the timing of vacuum application were examined: the vacuum was applied immediately, 5 s after, and 10 s after the sheet holder was lowered over the vacuum-forming stand. We measured mouthguard thickness at the labial surface of the central incisor, buccal surface of the first molar, and occlusal surface of the first molar. Differences in thickness in different regions of mouthguards formed under different timing of vacuum application were analyzed by two-way analysis of variance and Bonferroni method. RESULTS: We found that mouthguard thickness differed in different regions of the central incisors and the first molars (P < 0.01). The mouthguard thickness at the labial surface of the central incisor and buccal surface of the first molar became thinner when the vacuum was applied immediately after the sheet holder was lowered over the forming stand. The thickness at the occlusal surface of the first molar did not vary with the timing of vacuum application. CONCLUSIONS: Our results suggest that the thicknesses of the labial surface of the central incisor and buccal surface of the first molar became larger when the vacuum was applied several seconds after the sheet holder was lowered over the forming stand. This finding is necessary knowledge when forming a mouthguard sheet. PMID- 26542182 TI - Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets. AB - Cross-presentation is the mechanism by which exogenous Ag is processed for recognition by CD8(+) T cells. Murine CD8alpha(+) DCs are specialized at cross presenting soluble and cellular Ag, but in humans this process is poorly characterized. In this study, we examined uptake and cross-presentation of soluble and cellular Ag by human blood CD141(+) DCs, the human equivalent of mouse CD8alpha(+) DCs, and compared them with human monocyte-derived DCs (MoDCs) and blood CD1c(+) DC subsets. MoDCs were superior in their capacity to internalize and cross-present soluble protein whereas CD141(+) DCs were more efficient at ingesting and cross-presenting cellular Ag. Whilst cross presentation by CD1c(+) DCs and CD141(+) DCs was dependent on the proteasome, and hence cytosolic translocation, cross-presentation by MoDCs was not. Inhibition of endosomal acidification enhanced cross-presentation by CD1c(+) DCs and MoDCs but not by CD141(+) DCs. These data demonstrate that CD1c(+) DCs, CD141(+) DCs, and MoDCs are capable of cross-presentation; however, they do so via different mechanisms. Moreover, they demonstrate that human CD141(+) DCs, like their murine CD8alpha(+) DC counterparts, are specialized at cross-presenting cellular Ag, most likely mediated by an enhanced capacity to ingest cellular Ag combined with subtle changes in lysosomal pH during Ag processing and use of the cytosolic pathway. PMID- 26542184 TI - Identifying medical wearables and sensor technologies that deliver data on clinical endpoints. PMID- 26542183 TI - Dense sampling reveals behavioral oscillations in rapid visual categorization. AB - Perceptual systems must create discrete objects and events out of a continuous flow of sensory information. Previous studies have demonstrated oscillatory effects in the behavioral outcome of low-level visual tasks, suggesting a cyclic nature of visual processing as the solution. To investigate whether these effects extend to more complex tasks, a stream of "neutral" photographic images (not containing targets) was rapidly presented (20 ms/image). Embedded were one or two presentations of a randomly selected target image (vehicles and animals). Subjects reported the perceived target category. On dual-presentation trials, the ISI varied systematically from 0 to 600 ms. At randomized timing before first target presentation, the screen was flashed with the intent of creating a phase reset in the visual system. Sorting trials by temporal distance between flash and first target presentation revealed strong oscillations in behavioral performance, peaking at 5 Hz. On dual-target trials, longer ISIs led to reduced performance, implying a temporal integration window for object category discrimination. The "animal" trials exhibited a significant oscillatory component around 5 Hz. Our results indicate that oscillatory effects are not mere fringe effects relevant only with simple stimuli, but are resultant from the core mechanisms of visual processing and may well extend into real-life scenarios. PMID- 26542186 TI - Covalent bonding of homochiral metal-organic framework in capillaries for stereoisomer separation by capillary electrochromatography. AB - In this work, a [Cu(mal)(bpy)]?H2O (mal, L-(-)-malic acid; bpy, 4,4'-bipyridyl) homochiral metal-organic frameworks (MOFs) was synthesized and used for modifying the inner walls of capillary columns by utilizing amido bonds to form covalent links between the MOFs particles and capillary inner wall. The synthesized [Cu(mal)(bpy)]?H2 O and MOFs-modified capillary column were characterized by X ray diffraction, thermogravimetric analysis, particle size distribution analysis, nitrogen absorption characterization, FTIR spectroscopy, SEM, and energy dispersive X-ray spectroscopy (EDX). The MOFs-modified capillary column was used for the stereoisomer separation of some drugs. The LODs and LOQs of six analytes were 0.1 and 0.25 MUg/mL, respectively. The linear range was 0.25-250 MUg/mL for ephedrine, 0.25-250 MUg/mL for pseudoephedrine, 0.25-180 MUg/mL for D penicillamine, 0.25-120 MUg/mL for L-penicillamine, 0.25-180 MUg/mL for D phenylalanine, and 0.25-160 MUg/mL for L-phenylalanine, all with R(2) > 0.999. Finally, the MOFs-modified capillary column was applied for the analysis of active ingredients in a real sample of the traditional Chinese medicine ephedra. PMID- 26542187 TI - High-volume surgeons vs high-volume hospitals: are best outcomes more due to who or where? AB - BACKGROUND: High-volume hospitals are purported to provide "best" outcomes. We undertook this study to evaluate the outcomes after pancreaticoduodenectomy when high-volume surgeons relocate to a low-volume hospital (ie, no pancreaticoduodenectomies in >5 years). METHODS: Outcomes after the last 50 pancreaticoduodenectomies undertaken at a high-volume hospital in 2012 (ie, before relocation) were compared with the outcomes after the first 50 pancreaticoduodenectomies undertaken at a low-volume hospital (ie, after relocation) in 2012 to 2013. RESULTS: Patients undergoing pancreaticoduodenectomies at a high-volume vs a low-volume hospital were not different by age or sex. Patients who underwent pancreaticoduodenectomy at the low-volume hospital had shorter operations with less blood loss, spent less time in the intensive care unit, and had shorter length of stay (P < .05 for each); 30 day mortality and 30-day readmission rates were not different. CONCLUSIONS: The salutary benefits of undertaking pancreaticoduodenectomy at a high-volume hospital are transferred to a low-volume hospital when high-volume surgeons relocate. The "best" results follow high-volume surgeons. PMID- 26542185 TI - Preventing environmental enteric dysfunction through improved water, sanitation and hygiene: an opportunity for stunting reduction in developing countries. AB - In 2011, one in every four (26%) children under 5 years of age worldwide was stunted. The realization that most stunting cannot be explained by poor diet or by diarrhoea, nor completely reversed by optimized diet and reduced diarrhoea has led to the hypothesis that a primary underlying cause of stunting is subclinical gut disease. Essentially, ingested microbes set in motion two overlapping and interacting pathways that result in linear growth impairment. Firstly, partial villous atrophy results in a reduced absorptive surface area and loss of digestive enzymes. This in turn results in maldigestion and malabsorption of much needed nutrients. Secondly, microbes and their products make the gut leaky, allowing luminal contents to translocate into systemic circulation. This creates a condition of chronic immune activation, which (i) diverts nutrient resources towards the metabolically expensive business of infection fighting rather than growth; (ii) suppresses the growth hormone-IGF axis and inhibits bone growth, leading to growth impairment; and (iii) causes further damage to the intestinal mucosa thereby exacerbating the problem. As such, the unhygienic environments in which infants and young children live and grow must contribute to, if not be the overriding cause of, this environmental enteric dysfunction. We suggest that a package of baby-WASH interventions (sanitation and water improvement, handwashing with soap, ensuring a clean play and infant feeding environment and food hygiene) that interrupt specific pathways through which feco-oral transmission occurs in the first two years of a child's life may be central to global stunting reduction efforts. PMID- 26542188 TI - Insulin dependence as an independent predictor of perioperative morbidity after ventral hernia repair: a National Surgical Quality Improvement Program analysis of 45,759 patients. AB - BACKGROUND: Although diabetes mellitus has been identified as a predictor of perioperative morbidity after ventral hernia repair (VHR), it is unclear whether insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) confer the same degree of risk. We examined the variable effect of IDDM and NIDDM on 30-day medical and surgical complications after VHR. METHODS: We performed a retrospective analysis of patients in the National Surgical Quality Improvement Program database from 2005 to 2012 undergoing VHR. After perioperative variable comparison, regression analysis was performed to determine whether IDDM and/or NIDDM independently predicted increased complications after proper risk adjustment. RESULTS: A total of 45,759 patients were identified to have undergone VHR. Of these, 38,026 patients (83.1%) were not diabetic, 5,252 (11.5%) were NIDDM patients, and 2,481 (5.4%) were IDDM patients. After controlling for other risk factors, we found that IDDM independently predicted increased rates of overall, surgical, and medical complications (odds ratio, 1.284, 1.251, 1.263, respectively) in open repair. IDDM independently predicted increased overall and medical complications (odds ratio, 1.997, 1.889, respectively) but not surgical complications in laparoscopic repair. NIDDM was not significantly associated with any complication type in either procedure type. CONCLUSIONS: Our present study suggests that much of the perioperative risk associated with diabetes is attributable to IDDM. The effect of IDDM on laparoscopic and open repair is subtly different. IDDM demonstrates increased overall and medical complications in laparoscopic repair and increased overall, medical, and surgical complications in open repair. Of note, IDDM does not independently predict increased risk for surgical complications in laparoscopic repair. PMID- 26542189 TI - Postoperative complications and patient satisfaction: does payer status have an impact? AB - BACKGROUND: Patient demographics and outcomes may influence patient satisfaction. We aim to investigate the relationship between postoperative complications and survey-based satisfaction in the context of payer status. METHODS: Institutional data were used to identify major complication occurrence and linked to patient satisfaction surveys. The impact of complication occurrence on satisfaction was investigated and stratified by payer status. RESULTS: In all, 1,597 encounters were identified with an 18% major complication rate. Satisfaction scores in specific domains were significantly more likely to be above the median for patients without complications (P < .01) and for payer status Medicaid/low income (P < .05). In sensitivity analyses, we found no significant interactions among payer status, complications, and satisfaction scores. CONCLUSIONS: Significant differences exist for individual satisfaction survey domains between patients with and without major postoperative complications and by payer status. Payer status was not found to have an impact on the intersection of major complications and patient satisfaction. PMID- 26542190 TI - High-Strength Composite Fibers from Cellulose-Lignin Blends Regenerated from Ionic Liquid Solution. AB - Composite fibres that contain cellulose and lignin were produced from ionic liquid solutions by dry-jet wet spinning. Eucalyptus dissolving pulp and organosolv/kraft lignin blends in different ratios were dissolved in the ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate to prepare a spinning dope from which composite fibres were spun successfully. The composite fibres had a high strength with slightly decreasing values for fibres with an increasing share of lignin, which is because of the reduction in crystallinity. The total orientation of composite fibres and SEM images show morphological changes caused by the presence of lignin. The hydrophobic contribution of lignin reduced the vapour adsorption in the fibre. Thermogravimetric analysis curves of the composite fibres reveal the positive effect of the lignin on the carbonisation yield. Finally, the composite fibre was found to be a potential raw material for textile manufacturing and as a precursor for carbon fibre production. PMID- 26542191 TI - Delayed absorbable synthetic plug (GORE(r) BIO-A(r)) for the treatment of fistula in-ano: a systematic review. AB - AIM: Recent advances in the treatment of fistula-in-ano have focused on surgical techniques that preserve sphincter integrity. Plugs that obliterate the lumen of the fistula track have been proposed as one such method, and may be derived from biological or delayed absorbable synthetic materials. Biological plugs have highly variable results and have not been widely adopted. The aim of this systematic review was to assess the effectiveness and safety of a delayed absorbable synthetic plug (GORE(r) BIO-A(r)) for treatment of anal fistula. METHOD: A systematic review of all literature in the English language relevant to the use of a plug to treat anal fistula and published between 1 January 2008 and 15 February 2015 was carried out by searching MEDLINE, EMBASE and the Cochrane Library of Systematic Reviews/Controlled Trials for relevant literature. Relevant articles were identified, quality assessed using the methodological index for nonrandomized studies criteria and data were extracted by two independent researchers (SKN and NNA). The identified articles were assessed with regard to fistula healing rate, duration of follow-up and complication rates related to the use of delayed absorbable synthetic fistula plugs. RESULTS: Twenty six potential articles were identified from the literature search. Using the predefined inclusion and exclusion criteria, six were included in the final analysis, data extraction and data synthesis. Of these included in the review only three were prospective in design. Complete data were available for 187 of the 221 patients who underwent this treatment. The age of the participants ranged from 19 to 82 years. The fistula healing rates were reported to be between 15.8% and 72.7% at a follow-up ranging between 2 and 19 months. Early or delayed plug extrusion occurred in 16 (8.5%) of the 187 patients. Deterioration in continence was reported in 11 (5.8%) of 187 patients. CONCLUSION: There are insufficient high quality data on the delayed absorbable synthetic (GORE(r) BIO-A(r)) fistula plug to draw meaningful conclusions regarding its effectiveness. It does, however, appear to be a simple and safe technique associated with low complication rates and a minor deterioration in continence in a few cases. PMID- 26542192 TI - On-farm habitat restoration counters biotic homogenization in intensively managed agriculture. AB - To slow the rate of global species loss, it is imperative to understand how to restore and maintain native biodiversity in agricultural landscapes. Currently, agriculture is associated with lower spatial heterogeneity and turnover in community composition (beta-diversity). While some techniques are known to enhance alpha-diversity, it is unclear whether habitat restoration can re establish beta-diversity. Using a long-term pollinator dataset, comprising ~9,800 specimens collected from the intensively managed agricultural landscape of the Central Valley of California, we show that on-farm habitat restoration in the form of native plant 'hedgerows', when replicated across a landscape, can boost beta-diversity by approximately 14% relative to unrestored field margins, to levels similar to some natural communities. Hedgerows restore beta-diversity by promoting the assembly of phenotypically diverse communities. Intensively managed agriculture imposes a strong ecological filter that negatively affects several important dimensions of community trait diversity, distribution, and uniqueness. However, by helping to restore phenotypically diverse pollinator communities, small-scale restorations such as hedgerows provide a valuable tool for conserving biodiversity and promoting ecosystem services. PMID- 26542193 TI - Characteristics of Resting Metabolic Rate in Critically Ill, Mechanically Ventilated Adults With Cystic Fibrosis. AB - BACKGROUND: Critically ill patients with cystic fibrosis may be especially sensitive to the negative consequences of overfeeding and underfeeding, yet there is almost no information available about the energy needs of these patients. The purpose of this study was to characterize the metabolic rate of critically ill adult patients with cystic fibrosis requiring mechanical ventilation. METHODS: This was an observational study in which the resting metabolic rate, oxygen consumption, and carbon dioxide production of adult patients with cystic fibrosis requiring critical care, sedation, and mechanical ventilation were measured with indirect calorimetry. This group was compared with a cohort of adult critical care patients without cystic fibrosis. RESULTS: Twelve patients with cystic fibrosis were identified and measured. These were compared with a control group of 25 critically ill patients. Both groups were underweight (body mass index, 17.4 +/- 4.0 kg/m2 in cystic fibrosis and 18.4 +/- 2.3 kg/m2 in control). Adjusting for differences in age, sex, height, and weight, there was no difference in resting metabolic rate between the cystic fibrosis and control groups (1702 +/- 193 vs 1642 +/- 194 kcal/d, P = .388). Measured resting metabolic rate matched predicted values 58% of the time in cystic fibrosis and 60% of the time in control. CONCLUSIONS: The resting metabolic rate of sedated adult patients with cystic fibrosis being assisted with mechanical ventilation is not different from that of adult critical care patients without cystic fibrosis. In both these underweight groups, accurate prediction of resting metabolic rate is difficult to obtain. PMID- 26542194 TI - CdTe/ZnS quantum dots as fluorescent probes for ammonium determination. AB - Novel CdTe/ZnS quantum dot (QD) probes based on the quenching effect were proposed for the simple, rapid, and specific determination of ammonium in aqueous solutions. The QDs were modified using 3-mercaptopropionic acid, and the fluorescence responses of the CdTe/ZnS QD probes to ammonium were detected through regularity quenching. The quenching levels of the CdTe/ZnS QDs and ammonium concentration showed a good linear relationship between 4.0 * 10(-6) and 5.0 * 10(-4) mol/L; the detection limit was 3.0 * 10(-7) mol/L. Ammonium contents in synthetic explosion soil samples were measured to determine the practical applications of the QD probes and a probable quenching mechanism was described. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542195 TI - Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers. AB - BACKGROUND: The fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B-eos) are markers of eosinophilic inflammation used in the diagnosis and management of asthma. The relationships between smoking cigarette and both FENO and B-eos are complex and raise questions about the association between these markers and asthma in smokers. OBJECTIVE: To determine the relationships between both FENO and B-eos on one hand and asthma and atopy on the other, according to smoking status. METHODS: FENO and B-eos were measured in, respectively, 1579 and 1496 of the 1607 middle-aged adults randomly selected from the general population in the cross-sectional ELISABET survey. Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy (allergic rhinitis or hayfever in the previous 12 months, or a previous positive prick test or allergen desensitization therapy). Non-allergic asthma was defined as asthma without atopy. RESULTS: The analysis included 812 (51.4%) never, 473 (30%) former and 294 (18.6%) current smokers. A total of 490 (32%) participants were atopic, 80 (5.1%) had allergic asthma, and 31 (2%) had non-allergic asthma. Only 16.2% (18/111) of asthmatics were treated with glucocorticoid inhalants, suggesting that among them a majority of participants had mild asthma. A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO (P = 0.003) and B-eos (P = 0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+ 63.4%, 95% CI = [39; 92]) and higher B-eos (+ 63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. Lastly, an analysis of receiver-operating characteristic curves showed that each of the two markers was able to discriminate moderately allergic asthma but only in non-smokers. CONCLUSIONS & CLINICAL RELEVANCE: FENO and B-eos were associated with the presence of mild allergic asthma only in non-smokers, not in current smokers. These findings raise questions about the clinical value of FENO and B-eos in smokers. PMID- 26542196 TI - Use of dorsal intercostal artery perforator flap in the repair of back defects. AB - BACKGROUND: The dorsal intercostal artery perforator (DICAP) flap is a well vascularised flap that is elevated above the dorsal branch of the vertebral segments of the posterior intercostal artery. The aim of this study was to repair back defects using DICAP flaps. MATERIALS AND METHODS: Eight patients who had undergone reconstruction with DICAP flaps for defects located on the back of the torso due to conditions of various aetiologies between 2011-2014 were included in this study. Patient age and gender, aetiology of the condition, dimensions of the defect and the flap, site of the defect, and postoperative complications were recorded. RESULTS: Three females and five males were included in this study. The age of the patients ranged between 19-71 years (mean = 53.6 years). The aetiology was skin tumour in five patients and pressure wound, gunshot injury, and plate screw exposition subsequent to spinal surgery in one patient each. The sites of the defects were successfully closed in all patients, and no flap loss was observed in any patient. CONCLUSIONS: DICAP flaps have some advantages compared to conventional muscle and muscle skin flaps, such as greater protection of muscle functions, less invasiveness, and lower donor site morbidity. This flap has a high mobilisation capacity due to its elevation above nine bilateral perforator arteries. Therefore, the DICAP flap is useful for the repair of median and paramedian back defects. Based on its advantages, it is suggested that the DICAP flap should be considered as a useful option for the repair of back defects. PMID- 26542197 TI - Effect of socioeconomic deprivation on uptake of measles, mumps and rubella vaccination in Liverpool, UK over 16 years: a longitudinal ecological study. AB - Suboptimal uptake of the measles, mumps and rubella (MMR) vaccine by certain socioeconomic groups may have contributed to recent large measles outbreaks in the UK. We investigated whether socioeconomic deprivation was associated with MMR vaccine uptake over 16 years. Using immunization data for 72,351 children born between 1995 and 2012 in Liverpool, UK, we examined trends in vaccination uptake. Generalized linear models were constructed to examine the relative effect of socioeconomic deprivation and year of birth on MMR uptake. Uptake of MMR1 by age 24 months ranged between 82.5% in 2003 [95% confidence interval (CI) 81.2-83.7] and 93.4% in 2012 (95% CI 92.7-94.2). Uptake of MMR2 by age 60 months ranged between 65.3% (95% CI 64.4-67.4) in 2006 and 90.3% (95% CI 89.4-91.2) in 2012. In analysis adjusted for year of birth and sex, children in the most deprived communities were at significantly greater risk of not receiving MMR1 [risk ratio (RR) 1.70, 95% CI 1.45-1.99] and MMR2 (RR 1.36, 95% CI 1.22-1.52). Higher unemployment and lower household income were significantly associated with low uptake. Contrary to concerns about lower MMR uptake in affluent families, over 16 years, children from the most socioeconomically deprived communities have consistently had the lowest MMR uptake. Targeted catch-up campaigns and strategies to improve routine immunization uptake in deprived areas are needed to minimize the risk of future measles outbreaks. PMID- 26542198 TI - A high-performance liquid chromatography method for the serotonin release assay is equivalent to the radioactive method. AB - INTRODUCTION: The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method. METHODS: We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs. RESULTS: Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration. CONCLUSION: The HPLC-SRA has robust performance characteristics, equivalent to the historic radioactive method, but avoids the complexities of working with radioactivity. PMID- 26542199 TI - Structure-based virtual screening and experimental validation of the discovery of inhibitors targeted towards the human coronavirus nucleocapsid protein. AB - Nucleocapsid protein (NP), an essential RNA-binding viral protein in human coronavirus (CoV)-infected cells, is required for the replication and transcription of viral RNA. Recent studies suggested that human CoV NP is a valid target for antiviral drug development. Based on this aspect, structure-based virtual screening targeting nucleocapsid protein (NP) was performed to identify good chemical starting points for medicinal chemistry. The present study utilized structure-based virtual screening against human CoV-OC43 using the Zinc database, which is performed through docking with varying precisions and computational intensities to identify eight potential compounds. The chosen potential leads were further validated experimentally using biophysical means. Surface plasmon resonance (SPR) analysis indicated that one among the potential leads, 6-chloro-7 (2-morpholin-4-yl-ethylamino) quinoxaline-5,8-dione (small-compound H3), exhibited a significant decrease of RNA-binding capacity of NP by more than 20%. The loss of binding activity was manifested as a 20% decrease in the minimum on rate accompanied with a 70% increase in the maximum off-rate. Fluorescence titration and X-ray crystallography studies indicated that H3 antagonizes the binding between HCoV-OC43 NP and RNA by interacting with the N-terminal domain of the NP. Our findings provide insight into the development of new therapeutics that disrupt the interaction between RNA and viral NP in the HCoV. The discovery of the new compound would be an impetus to design novel NP inhibitors against human CoV. PMID- 26542200 TI - Is Arthroscopy Techniques Podium Material? Is Arthroscopy Techniques Biased? PMID- 26542201 TI - Anterior Cruciate Ligament Preservation: Early Results of a Novel Arthroscopic Technique for Suture Anchor Primary Anterior Cruciate Ligament Repair. AB - PURPOSE: To propose a technique of arthroscopic suture anchor primary anterior cruciate ligament (ACL) preservation for patients with proximal avulsion ACL tears that maintain excellent tissue quality. METHODS: We performed a retrospective review and early follow-up of 11 consecutive cases of ACL preservation. Patients were included if they had a proximal avulsion tear and excellent tissue quality confirmed to be adequate for repair during arthroscopy. Patients were excluded if these criteria were not met or if patients had multiligamentous injury patterns or significant arthrosis. The ACL was reinforced with a No. 2 FiberWire (Arthrex, Naples, FL) and a No. 2 TigerWire (Arthrex) and was anchored to the femoral footprint by two 4.75-mm BioComposite SwiveLock suture anchors (Arthrex). The surgical procedures were performed at 3 different hospitals by a single surgeon. Anterior stability was determined with a KT-1000 arthrometer (MEDmetric, San Diego, CA). Clinical outcomes were measured using the Lysholm score, modified Cincinnati score, Tegner activity score, Single Assessment Numeric Evaluation, and subjective and objective International Knee Documentation Committee (IKDC) scores. RESULTS: Ten of eleven patients had good subjective and clinical outcomes after ACL preservation surgery at a minimum of 2 years' and mean of 3.5 years' follow-up. The mean Lysholm score was 93.2; the mean modified Cincinnati score was 91.5; the preoperative Tegner activity score was maintained postoperatively in 8 of 10 patients; the mean Single Assessment Numeric Evaluation score was 91.5; the mean subjective IKDC score was 86.4; and the objective IKDC score was A in 9 of 11 patients, B in 1 patient, and C in 1 patient. KT-1000 measurements were available in 8 of 11 patients, with 7 of 8 showing a side-to-side difference of less than 3 mm on maximum manual testing and 1 showing a 6-mm difference. CONCLUSIONS: Preservation of the native ACL using the described arthroscopic primary repair technique can achieve short-term clinical success in a carefully selected subset of patients with proximal avulsion-type tears and excellent tissue quality. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26542202 TI - Editorial Commentary: Anterior Cruciate Ligament Primary Repair, Revisited. AB - Anterior cruciate ligament (ACL) primary repair shows good results at 2-year follow-up for proximal tears with good tissue quality. History teaches us to remain cautious pending 5-year follow-up. PMID- 26542203 TI - Editorial Commentary: Platelet-Rich Plasma Improves Knee Pain and Function in Patients With Knee Osteoarthritis. AB - Systematic review of overlapping meta-analyses shows that platelet-rich plasma improves knee pain and function in patients with knee osteoarthritis. Ultimately, biologics hold promise for chondroprotection in addition to symptomatic relief. PMID- 26542204 TI - Editorial Commentary: Arthroscopic-Assisted Treatment of Ankle Fractures Could Have Benefits That Outweigh the Risks. AB - Review of ankle arthroscopy, as an adjunct during ankle fracture open reduction and internal fixation, suggests that the benefits may outweigh the risks, because cartilage injury and other soft-tissue pathology amenable to arthroscopic treatment are common in patients with fracture of the ankle. PMID- 26542205 TI - Editorial Commentary: Anterior Cruciate Ligament Primary Repair Is a Holy Grail. AB - Anterior cruciate ligament primary repair shows preclinical promise, but favorable clinical outcomes have yet to be reported over the long term. PMID- 26542206 TI - Editorial Commentary: The Medial Side of the Knee Is Amenable to Repair. AB - Systematic review of knee medial collateral ligament (MCL) and posteromedial corner (PMC) "repair" finds low failure rates. PMID- 26542207 TI - Editorial Commentary: Medial Collateral Ligament and Posteromedial Corner Reconstruction Techniques Vary and Indications Are Not Clear. AB - Medial collateral ligament (MCL) and posteromedial corner (PMC) reconstruction techniques vary. Anatomic reconstruction results in outcomes superior to nonanatomic reconstruction, but it remains unclear as to when reconstruction is indicated versus MCL and PMC primary repair. PMID- 26542208 TI - Editorial Commentary: Rotator Cuff Repair Imaging Shows Retear at 1 Year Follow up. AB - Based on robust numbers and strict methods to reduce selection bias, systematic review shows that single-row rotator cuff repair results in a higher rate of retear at 1 year than does double-row or transosseous equivalent techniques. It makes some sense to speculate that retear could diminish long-term clinical outcome. However, when combining all tear sizes, the statistical differences in single-row retear rates appear graphically less significant. PMID- 26542209 TI - Isolation of a Wickerhamomyces anomalus yeast strain from the sandfly Phlebotomus perniciosus, displaying the killer phenotype. AB - The yeast Wickerhamomyces anomalus has been studied for its wide biotechnological potential, mainly for applications in the food industry. Different strains of W. anomalus have been isolated from diverse habitats and recently from insects, including mosquitoes of medical importance. This paper reports the isolation and phylogenetic characterization of W. anomalus from laboratory-reared adults and larvae of Phlebotomus perniciosus (Diptera: Psychodidae), a main phlebotomine vector of human and canine leishmaniasis. Of 65 yeast strains isolated from P. perniciosus, 15 strains were identified as W. anomalus; one of these was tested for the killer phenotype and demonstrated inhibitory activity against four yeast sensitive strains, as reported for mosquito-isolated strains. The association between P. perniciosus and W. anomalus deserves further investigation in order to explore the possibility that this yeast may exert inhibitory/killing activity against Leishmania spp. PMID- 26542210 TI - Identification of DNA lesions using a third base pair for amplification and nanopore sequencing. AB - Damage to the genome is implicated in the progression of cancer and stress induced diseases. DNA lesions exist in low levels, and cannot be amplified by standard PCR because they are frequently strong blocks to polymerases. Here, we describe a method for PCR amplification of lesion-containing DNA in which the site and identity could be marked, copied and sequenced. Critical for this method is installation of either the dNaM or d5SICS nucleotides at the lesion site after processing via the base excision repair process. These marker nucleotides constitute an unnatural base pair, allowing large quantities of marked DNA to be made by PCR amplification. Sanger sequencing confirms the potential for this method to locate lesions by marking, amplifying and sequencing a lesion in the KRAS gene. Detection using the alpha-hemolysin nanopore is also developed to analyse the markers in individual DNA strands with the potential to identify multiple lesions per strand. PMID- 26542211 TI - Alcohol consumption and the risk of Barrett's esophagus: a comprehensive meta analysis. AB - Several studies have been proposed to investigate the association between alcohol consumption and risk of Barrett's esophagus (BE), but as of yet, no quantitative summary of the literature to clarify the relationship between them. In our study, twenty eligible cohort studies involving 42925 participants were identified. Combined relative risk (RR) ratios for the highest versus lowest alcohol consumption levels were calculated. The alcohol dose-response analysis was performed to investigate the association between the increment consumption of 10 g/d alcohol and the risk of developing BE. Subgroup analyses were used to examine heterogeneity across the studies. A combined RR of 0.98 (0.62-1.34) was found when comparing highest vs. lowest alcohol consumption levels for BE. An inverse association between alcohol and incidence of BE (RR 0.51; 95% CI: 0.055-0.96) was demonstrated in women. Moreover, Asian drinkers had a relative higher risk of BE (RR 1.34; 95% CI: 1.11-1.56) compared with Western drinkers. In conclusion, our results showed that overall alcohol consumption was not associated with increased BE incidence. The limited data available on alcohol consumption supports a tentative inversion of alcohol consumption with BE risk in women, while Asian drinkers tend to have a higher risk of BE. PMID- 26542212 TI - Lignosus rhinocerotis (Cooke) Ryvarden mimics the neuritogenic activity of nerve growth factor via MEK/ERK1/2 signaling pathway in PC-12 cells. AB - The traditional application of the sclerotium of Lignosus rhinocerotis (tiger's milk mushroom) by the indigenous folks as tonic and remedy to treat a variety of ailments has been documented in Malaysia. Indigenous communities claimed to have consumed the decoction to boost their alertness during hunting. Mental alertness is believed to be related to neuronal health and neuroactivity. In the present study, the cell viability and neuritogenic effects of L. rhinocerotis sclerotium hot aqueous and ethanolic extracts, and crude polysaccharides on rat pheochromocytoma (PC-12) cells were studied. Interestingly, the hot aqueous extract exhibited neuritogenic activity comparable to NGF in PC-12 cells. However, the extracts and crude polysaccharides stimulated neuritogenesis without stimulating the production of NGF in PC-12 cells. The involvements of the TrkA receptor and MEK/ERK1/2 pathway in hot aqueous extract-stimulated neuritogenesis were examined by Trk (K252a) and MEK/ERK1/2 (U0126 and PD98059) inhibitors. There was no significant difference in protein expression in NGF- and hot aqueous extract-treated cells for both total and phosphorylated p44/42 MAPK. The neuritogenic activity in PC-12 cells stimulated by hot aqueous and ethanolic extracts, and crude polysaccharides of L. rhinocerotis sclerotium mimicking NGF activity via the MEK/ERK1/2 signaling pathway is reported for the first time. PMID- 26542213 TI - Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications. AB - Altered nitric oxide (*NO) metabolism underlies cancer pathology, but mechanisms explaining many *NO-associated phenotypes remain unclear. We have found that cellular exposure to *NO changes histone posttranslational modifications (PTM) by directly inhibiting the catalytic activity of JmjC-domain containing histone demethylases. Herein, we describe how *NO exposure links modulation of histone PTMs to gene expression changes that promote oncogenesis. Through high-resolution mass spectrometry, we generated an extensive map of *NO-mediated histone PTM changes at 15 critical lysine residues on the core histones H3 and H4. Concomitant microarray analysis demonstrated that exposure to physiologic *NO resulted in the differential expression of over 6,500 genes in breast cancer cells. Measurements of the association of H3K9me2 and H3K9ac across genomic loci revealed that differential distribution of these particular PTMs correlated with changes in the level of expression of numerous oncogenes, consistent with epigenetic code. Our results establish that *NO functions as an epigenetic regulator of gene expression mediated by changes in histone PTMs. PMID- 26542214 TI - Connexin 43 Inhibition Sensitizes Chemoresistant Glioblastoma Cells to Temozolomide. AB - Resistance of glioblastoma (GBM) to the front-line chemotherapeutic agent temozolomide (TMZ) continues to challenge GBM treatment efforts. The repair of TMZ-induced DNA damage by O-6-methylguanine-DNA methyltransferase (MGMT) confers one mechanism of TMZ resistance. Paradoxically, MGMT-deficient GBM patients survive longer despite still developing resistance to TMZ. Recent studies indicate that the gap junction protein connexin 43 (Cx43) renders GBM cells resistant to TMZ through its carboxyl terminus (CT). In this study, we report insights into how Cx43 promotes TMZ resistance. Cx43 levels were inversely correlated with TMZ sensitivity of GBM cells, including GBM stem cells. Moreover, Cx43 levels inversely correlated with patient survival, including as observed in MGMT-deficient GBM patients. Addition of the C-terminal peptide mimetic alphaCT1, a selective inhibitor of Cx43 channels, sensitized human MGMT-deficient and TMZ resistant GBM cells to TMZ treatment. Moreover, combining alphaCT1 with TMZ blocked AKT/mTOR signaling, induced autophagy and apoptosis in TMZ-resistant GBM cells. Our findings suggest that Cx43 may offer a biomarker to predict the survival of patients with MGMT-independent TMZ resistance and that combining a Cx43 inhibitor with TMZ could enhance therapeutic responses in GBM, and perhaps other TMZ-resistant cancers. PMID- 26542216 TI - Parachute-Like Mitral Valve with Symptomatic Stenosis--Imaging with Transthoracic and Transesophageal Three-Dimensional Echocardiography and Treatment Implications. PMID- 26542215 TI - Naturally Occurring Isothiocyanates Exert Anticancer Effects by Inhibiting Deubiquitinating Enzymes. AB - The anticancer properties of cruciferous vegetables are well known and attributed to an abundance of isothiocyanates such as benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). While many potential targets of isothiocyanates have been proposed, a full understanding of the mechanisms underlying their anticancer activity has remained elusive. Here we report that BITC and PEITC effectively inhibit deubiquitinating enzymes (DUB), including the enzymes USP9x and UCH37, which are associated with tumorigenesis, at physiologically relevant concentrations and time scales. USP9x protects the antiapoptotic protein Mcl-1 from degradation, and cells dependent on Mcl-1 were especially sensitive to BITC and PEITC. These isothiocyanates increased Mcl-1 ubiquitination and either isothiocyanate treatment, or RNAi-mediated silencing of USP9x decreased Mcl-1 levels, consistent with the notion that USP9x is a primary target of isothiocyanate activity. These isothiocyanates also increased ubiquitination of the oncogenic fusion protein Bcr-Abl, resulting in degradation under low isothiocyanate concentrations and aggregation under high isothiocyanate concentrations. USP9x inhibition paralleled the decrease in Bcr-Abl levels induced by isothiocyanate treatment, and USP9x silencing was sufficient to decrease Bcr-Abl levels, further suggesting that Bcr-Abl is a USP9x substrate. Overall, our findings suggest that USP9x targeting is critical to the mechanism underpinning the well-established anticancer activity of isothiocyanate. We propose that the isothiocyanate-induced inhibition of DUBs may also explain how isothiocyanates affect inflammatory and DNA repair processes, thus offering a unifying theme in understanding the function and useful application of isothiocyanates to treat cancer as well as a variety of other pathologic conditions. PMID- 26542217 TI - Late age increase in soluble amyloid-beta levels in the APP23 mouse model despite steady-state levels of amyloid-beta-producing proteins. PMID- 26542218 TI - Intimate partner violence and termination of pregnancy: a cross-sectional study of married Bangladeshi women. AB - BACKGROUND: The prevalence of intimate partner violence (IPV) and its consequences on women's reproductive health and pregnancy outcomes have been well documented. Bangladesh is burdened with the high prevalence of IPV and induced abortion/menstrual regulation. Understanding their association may benefit strategies to reduce termination of pregnancy (TOP). Therefore, this study assesses the association between experience of IPV and TOP among married Bangladeshi women age 15-49 years. METHODS: This cross-sectional study is based on data from 10,146 married women of reproductive age from the Bangladesh Demographic Health Survey, 2007 (BDHS). A subset of interviews from currently married women, living with a husband and who had at least one pregnancy in the last 5 years (n = 1875) were extracted. RESULTS: Results of this study showed that among the respondents, 31.4 % experienced physical and/or sexual IPV: 13.4 % experienced only sexual violence and 25.8 % experienced only physical violence. 21.0 % respondents ever had a TOP and 5.8 % had a TOP in last 5 years. Physical IPV was significantly associated with both TOP ever (OR = 1.36; 95 % CI: 1.05 1.77) and TOP in last 5 years (OR = 1.72; 95 % CI: 1.11-2.06). CONCLUSIONS: Prevention of intimate partner violence which was associated with pregnancy termination may reduce the high incidence of termination of pregnancies in Bangladesh. PMID- 26542219 TI - Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population. AB - We investigate the role of killer immunoglobulin-like receptor (KIR) genes and human leukocyte antigen class-I (HLA) variants in susceptibility to tuberculosis in a South African population. In a sample set comprising 408 TB cases and 351 healthy controls, we show that the KIR3DS1 gene and KIR genotypes with five or more activating KIRs, and the presence of 3DS1, protect against developing active TB in the South African Coloured population. Several HLA class-I alleles were identified as susceptibility factors for TB disease. However, none of the KIR-HLA compound genotypes were found to be associated with TB. Our data suggests that the KIR genes may play an important role in TB disease. PMID- 26542220 TI - Translational misreading in Mycobacterium smegmatis increases in stationary phase. AB - The study of errors in gene translation has largely been confined to a small number of model organisms. We have examined all possible misreading errors at a defined codon in Mycobacterium smegmatis. Using a dual-luciferase gain of function reporter system that employs a mutated essential lysine in firefly luciferase, we accurately quantified mistranslation errors. Overall, accuracy of gene translation was comparable with Escherichia coli at <1/2000 errors/codon during exponential growth. Stationary phase was associated with a dramatic increase in misincorporation errors by Lys-tRNACUU(Lys) at a subset of three codons, each with a single base changed from the AAG lysine codon. The maximum error rate detected was 0.2% with codon AUG. Treatment with streptomycin increased misreading errors at several codons associated in particular with U.U, G.U and C.U codon.anti-codon mismatches, but oxidative stress did not change translational fidelity. Our study is the first comprehensive examination of misreading errors for a defined codon in mycobacteria. PMID- 26542221 TI - Whole genome sequence analysis of Mycobacterium suricattae. AB - Tuberculosis occurs in various mammalian hosts and is caused by a range of different lineages of the Mycobacterium tuberculosis complex (MTBC). A recently described member, Mycobacterium suricattae, causes tuberculosis in meerkats (Suricata suricatta) in Southern Africa and preliminary genetic analysis showed this organism to be closely related to an MTBC pathogen of rock hyraxes (Procavia capensis), the dassie bacillus. Here we make use of whole genome sequencing to describe the evolution of the genome of M. suricattae, including known and novel regions of difference, SNPs and IS6110 insertion sites. We used genome-wide phylogenetic analysis to show that M. suricattae clusters with the chimpanzee bacillus, previously isolated from a chimpanzee (Pan troglodytes) in West Africa. We propose an evolutionary scenario for the Mycobacterium africanum lineage 6 complex, showing the evolutionary relationship of M. africanum and chimpanzee bacillus, and the closely related members M. suricattae, dassie bacillus and Mycobacterium mungi. PMID- 26542223 TI - Modulation of pro- and anti-inflammatory cytokines in active and latent tuberculosis by coexistent Strongyloides stercoralis infection. AB - Helminth infections are known to induce modulation of both innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating systemic cytokine responses in active and latent tuberculosis (LTB) is not known. To define the systemic cytokine levels in helminth-TB coinfection, we measured the circulating plasma levels of Type 1, Type 2, Type 17, other pro-inflammatory and regulatory cytokines in individuals with active TB (ATB) with or without coexistent Strongyloides stercoralis (Ss) infection by multiplex ELISA. Similarly, we also measured the same cytokine levels in individuals with LTB with or without concomitant Ss infection in a cross-sectional study. Our data reveal that individuals with ATB or LTB and coexistent Ss infection have significantly lower levels of Type 1 (IFNgamma, TNFalpha and IL-2) and Type 17 (IL-17A and IL-17F) cytokines compared to those without Ss infection. In contrast, those with ATB and LTB with Ss infection have significantly higher levels of the regulatory cytokines (IL-10 and TGFbeta), and those with LTB and Ss infection also have significantly higher levels of Type 2 cytokines (IL-4, IL-5 and IL-13) as well. Finally, those with LTB (but not ATB) exhibit significantly lower levels of other pro-inflammatory cytokines (IFNalpha, IFNbeta, IL-6, IL-12 and GM-CSF). Our data therefore reveal a profound effect of Ss infection on the systemic cytokine responses in ATB and LTB and indicate that coincident helminth infections might influence pathogenesis of TB infection and disease. PMID- 26542222 TI - Whole genome sequencing identifies circulating Beijing-lineage Mycobacterium tuberculosis strains in Guatemala and an associated urban outbreak. AB - Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistance, but there have been only a few cases reported in Central America. Here we report the first whole genome sequencing of Central American Beijing-lineage strains of Mtb. We find that multiple Beijing-lineage strains, derived from independent founding events, are currently circulating in Guatemala, but overall still represent a relatively small proportion of disease burden. Finally, we identify a specific Beijing-lineage outbreak centered on a poor neighborhood in Guatemala City. PMID- 26542224 TI - An investigation on the population structure of mixed infections of Mycobacterium tuberculosis in Inner Mongolia, China. AB - OBJECTIVES: Mixed infections of Mycobacterium tuberculosis strains have attracted more attention due to their increasing frequencies worldwide, especially in the areas of high tuberculosis (TB) prevalence. In this study, we accessed the rates of mixed infections in a setting with high TB prevalence in Inner Mongolia Autonomous Region of China. METHODS: A total of 384 M. tuberculosis isolates from the local TB hospital were subjected to mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing method. The single clones of the strains with mixed infections were separated by subculturing them on the Lowenstein-Jensen medium. RESULTS: Of these 384 isolates, twelve strains (3.13%) were identified as mixed infections by MIRU-VNTR. Statistical analysis indicated that demographic characteristics and drug susceptibility profiles showed no statistically significant association with the mixed infections. We further subcultured the mixed infection strains and selected 30 clones from the subculture for each mixed infection. Genotyping data revealed that eight (8/12, 66.7%) strains with mixed infections had converted into single infection through subculture. The higher growth rate was associated with the increasing proportion of variant subpopulation through subculture. CONCLUSIONS: In conclusion, by using the MIRU-VNTR method, we demonstrate that the prevalence of mixed infections in Inner Mongolia is low. Additionally, our findings reveal that the subculture changes the population structures of mixed infections, and the subpopulation with higher growth rate show better fitness, which is associated with high proportion among the population structure after subculture. This study highlights that the use of clinical specimens, rather than subcultured isolates, is preferred to estimate the prevalence of mixed infections in the specific regions. PMID- 26542225 TI - CASTB (the comprehensive analysis server for the Mycobacterium tuberculosis complex): A publicly accessible web server for epidemiological analyses, drug resistance prediction and phylogenetic comparison of clinical isolates. PMID- 26542226 TI - An economic evaluation of expanding hookworm control strategies to target the whole community. AB - BACKGROUND: The WHO treatment guidelines for the soil-transmitted helminths (STH) focus on targeting children for the control of morbidity induced by heavy infections. However, unlike the other STHs, the majority of hookworm infections are harboured by adults. This untreated burden may have important implications for controlling both hookworm's morbidity and transmission. This is particularly significant in the context of the increased interest in investigating STH elimination strategies. METHODS: We used a deterministic STH transmission model and parameter estimates derived from field epidemiological studies to evaluate the impact of child-targeted (2-14 year olds) versus community-wide treatment against hookworm in terms of preventing morbidity and the timeframe for breaking transmission. Furthermore, we investigated how mass treatment may influence the long-term programmatic costs of preventive chemotherapy for hookworm. RESULTS: The model projected that a large proportion of the overall morbidity due to hookworm was unaffected by the current child-targeted strategy. Furthermore, driving worm burdens to levels low enough to potentially break transmission was only possible when using community-wide treatment. Due to these projected reductions in programme duration, it was possible for community-wide treatment to generate cost savings - even if it notably increases the annual distribution costs. CONCLUSIONS: Community-wide treatment is notably more cost-effective for controlling hookworm's morbidity and transmission than the current child-targeted strategies and could even be cost-saving in many settings in the longer term. These calculations suggest that it is not optimum to treat using the same treatment strategies as other STH. Hookworm morbidity and transmission control require community-wide treatment. PMID- 26542227 TI - Responsive Aqueous Foams Stabilized by Silica Nanoparticles Hydrophobized in Situ with a Conventional Surfactant. AB - In the recent past, switchable surfactants and switchable/stimulus-responsive surface-active particles have been of great interest. Both can be transformed between surface-active and surface-inactive states via several triggers, making them recoverable and reusable afterward. However, the synthesis of these materials is complicated. In this paper we report a facile protocol to obtain responsive surface-active nanoparticles and their use in preparing responsive particle-stabilized foams. Hydrophilic silica nanoparticles are initially hydrophobized in situ with a trace amount of a conventional cationic surfactant in water, rendering them surface-active such that they stabilize aqueous foams. The latter can then be destabilized by adding equal moles of an anionic surfactant, and restabilized by adding another trace amount of the cationic surfactant followed by shaking. The stabilization-destabilization of the foams can be cycled many times at room temperature. The trigger is the stronger electrostatic interaction between the oppositely charged surfactants than that between the cationic surfactant and the negatively charged particles. The added anionic surfactant tends to form ion pairs with the cationic surfactant, leading to desorption of the latter from particle surfaces and dehydrophobization of the particles. Upon addition of another trace amount of cationic surfactant, the particles are rehydrophobized in situ and can then stabilize foams again. This principle makes it possible to obtain responsive surface-active particles using commercially available inorganic nanoparticles and conventional surfactants. PMID- 26542229 TI - Engineering oxygen vacancies towards self-activated BaLuAl(x)Zn(4-x)O(7-(1-x)/2) photoluminescent materials: an experimental and theoretical analysis. AB - Novel self-activated yellow-emitting BaLuAlxZn4-xO7-(1-x)/2 photoluminescent materials were investigated by a combined experimental and theoretical analysis. The effects of Al/Zn composition modulation, calcination atmosphere and temperature on the crystal structure and photoluminescence properties have been studied via engineering oxygen vacancies. Accordingly, BaLuAl0.91Zn3.09O7 prepared in an air atmosphere was found to be the stable crystalline phase with optimal oxygen content and gave a broad yellow emission band with a maximum at 528 nm. The self-activated luminescence mechanism is ascribed to the O-vacancies based on the density functional theory (DFT) calculation. A theoretical model originating from the designed oxygen vacancies has been proposed in order to determine the influence of O-vacancies on the band structure and self-activated luminescence. Therefore, the appearance of a new local energy level in the band gap will cause the wide-band optical transitions in the studied BaLuAlxZn4-xO7-(1 x)/2 materials. PMID- 26542230 TI - Electrochemical Measurement of the beta-Galactosidase Reporter from Live Cells: A Comparison to the Miller Assay. AB - In order to match our ability to conceive of and construct cells with enhanced function, we must concomitantly develop facile, real-time methods for elucidating performance. With these, new designs can be tested in silico and steps in construction incrementally validated. Electrochemical monitoring offers the above advantages largely because signal transduction stems from direct electron transfer, allowing for potentially quicker and more integrated measurements. One of the most common genetic reporters, beta-galactosidase, can be measured both spectrophotometrically (Miller assay) and electrochemically. However, since the relationship between the two is not well understood, the electrochemical methods have not yet garnered the attention of biologists. With the aim of demonstrating the utility of an electrochemical measurement to the synthetic biology community, we created a genetic construct that interprets and reports (with beta galactosidase) on the concentration of the bacterial quorum sensing molecule autoinducer-2. In this work, we provide a correlation between electrochemical measurements and Miller Units. We show that the electrochemical assay works with both lysed and whole cells, allowing for the prediction of one from the other, and for continuous monitoring of cell response. We further present a conceptually simple and generalized mathematical model for cell-based beta-galactosidase reporter systems that could aid in building and predicting a variety of synthetic biology constructs. This first-ever in-depth comparison and analysis aims to facilitate the use of electrochemical real-time monitoring in the field of synthetic biology as well as to facilitate the creation of constructs that can more easily communicate information to electronic systems. PMID- 26542228 TI - A multi-omic analysis of human naive CD4+ T cells. AB - BACKGROUND: Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases. Nevertheless, a unified analysis of the genome, epigenome, transcriptome and proteome of a single human cell type to obtain a coherent view of the complex interplay between various biomolecules has not yet been undertaken. Here, we report the first multi-omic analysis of human primary naive CD4+ T cells isolated from a single individual. RESULTS: Integrating multi-omics datasets allowed us to investigate genome-wide methylation and its effect on mRNA/protein expression patterns, extent of RNA editing under normal physiological conditions and allele specific expression in naive CD4+ T cells. In addition, we carried out a multi-omic comparative analysis of naive with primary resting memory CD4+ T cells to identify molecular changes underlying T cell differentiation. This analysis provided mechanistic insights into how several molecules involved in T cell receptor signaling are regulated at the DNA, RNA and protein levels. Phosphoproteomics revealed downstream signaling events that regulate these two cellular states. Availability of multi-omics data from an identical genetic background also allowed us to employ novel proteogenomics approaches to identify individual-specific variants and putative novel protein coding regions in the human genome. CONCLUSIONS: We utilized multiple high-throughput technologies to derive a comprehensive profile of two primary human cell types, naive CD4+ T cells and memory CD4+ T cells, from a single donor. Through vertical as well as horizontal integration of whole genome sequencing, methylation arrays, RNA-Seq, miRNA-Seq, proteomics, and phosphoproteomics, we derived an integrated and comparative map of these two closely related immune cells and identified potential molecular effectors of immune cell differentiation following antigen encounter. PMID- 26542232 TI - Erratum. PMID- 26542231 TI - Favorable Bridging Therapy Based on DWI-FLAIR Mismatch in Patients with Unclear Onset Stroke. AB - BACKGROUND AND PURPOSE: Standard selection criteria for revascularization therapy usually exclude patients with unclear-onset stroke. Our aim was to evaluate the efficacy and safety of revascularization therapy in patients with unclear-onset stroke in the anterior circulation and to identify the predictive factors for favorable clinical outcome. MATERIALS AND METHODS: We retrospectively analyzed 41 consecutive patients presenting with acute stroke with unknown time of onset treated by intravenous thrombolysis and/or mechanical thrombectomy. Only patients without well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions on MR imaging were enrolled. Twenty-one patients were treated by intravenous thrombolysis; 19 received, simultaneously, intravenous thrombolysis and mechanical thrombectomy (as a bridging therapy); and 1 patient, endovascular therapy alone. Clinical outcome was evaluated at 90 days by using the mRS. Mortality and symptomatic intracranial hemorrhage were also reported. RESULTS: Median patient age was 72 years (range, 17-89 years). Mean initial NIHSS score was 14.5 +/- 5.7. Successful recanalization (TICI 2b-3) was assessed in 61% of patients presenting with an arterial occlusion, symptomatic intracranial hemorrhage occurred in 2 patients (4.9%), and 3 (7.3%) patients died. After 90 days, favorable outcome (mRS 0-2) was observed in 25 (61%) patients. Following multivariate analysis, initial NIHSS score (OR, 1.43; 95% CI, 1.13-1.82; P = .003) and bridging therapy (OR, 37.92; 95% CI, 2.43-591.35; P = .009) were independently associated with a favorable outcome at 3 months. CONCLUSIONS: The study demonstrates the safety and good clinical outcome of acute recanalization therapy in patients with acute stroke in the anterior circulation and an unknown time of onset and a DWI/FLAIR mismatch on imaging. Moreover, bridging therapy versus intravenous thrombolysis alone was independently associated with favorable outcome at 3 months. PMID- 26542233 TI - Mechanical Thrombectomy of Distal Occlusions in the Anterior Cerebral Artery: Recanalization Rates, Periprocedural Complications, and Clinical Outcome. AB - BACKGROUND AND PURPOSE: Patients with acute ischemic stroke in the anterior circulation are at risk for either primary or, following mechanical thrombectomy, secondary occlusion of the anterior cerebral artery. Because previous studies had only a limited informative value, we report our data concerning the frequency and location of distal anterior cerebral artery occlusions, recanalization rates, periprocedural complications, and clinical outcome. MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data of patients with acute ischemic stroke undergoing mechanical thrombectomy in the anterior circulation between June 2010 and April 2015. RESULTS: Of 368 patients included in this analysis, we identified 30 (8.1%) with either primary (n = 17, 4.6%) or secondary (n = 13, 3.5%) embolic occlusion of the distal anterior cerebral artery. The recanalization rate after placement of a stent retriever was 88%. Periprocedural complications were rare and included vasospasms (n = 3, 10%) and dissection (n = 1, 3.3%). However, 16 (53.5%) patients sustained an (at least partial) infarction of the anterior cerebral artery territory. Ninety days after the ictus, clinical outcome according to the modified Rankin Scale score was the following: 0-2, n = 11 (36.6%); 3-4, n = 9 (30%); 5-6, n = 10 (33.3%). CONCLUSIONS: Occlusions of the distal anterior cerebral artery affect approximately 8% of patients with acute ischemic stroke in the anterior circulation receiving mechanical thrombectomy. Despite a high recanalization rate and a low complication rate, subsequent (partial) infarction in the anterior cerebral artery territory occurs in approximately half of patients. Fortunately, clinical outcome appears not to be predominately unfavorable. PMID- 26542234 TI - Structural Brain Alterations in Community Dwelling Individuals with Chronic Joint Pain. AB - BACKGROUND AND PURPOSE: Central sensitization in chronic pain involves structural brain changes that influence vulnerability to pain. Identifying brain regions involved in pain processing and sensitization can provide more insight into chronic pain. This study examines structural brain changes in chronic pain and experimental pain in a large population-based study. MATERIALS AND METHODS: For 3892 participants in the Rotterdam study, global and regional MR imaging brain volumes were automatically segmented and quantified. Chronic joint pain was defined as pain for more than half of all days during the past 6 weeks. Heat pain thresholds were measured in a subset of 1538 individuals. The association between the presence of chronic joint pain and global and lobar brain volumes was studied. Subsequently, literature was reviewed and the association of chronic pain and heat pain thresholds with 11 brain regions associated with musculoskeletal pain in previous publications was studied. RESULTS: Total gray matter volume was smaller in women with chronic pain (beta = -0.066, P = .016). This effect was primarily driven by lower gray matter volume in the temporal lobe (beta = 0.086, P = .005), the frontal lobe (beta = -0.060, P = .039), and the hippocampus (beta = -0.099, P = .002). In addition, we observed that a lower heat pain threshold was associated with smaller volumes of the hippocampus (beta = 0.017, P = .048), the thalamus (beta = 0.018, P = .009), and the anterior cingulate cortex (beta = -0.016, P = .037). In men, no significant associations were observed. CONCLUSIONS: The primary identified brain areas, the temporal and frontal lobes and the hippocampus, indicated involvement of emotional processing. The volumetric differences found indicated a sex-specific neuroplasticity in chronic pain. These results emphasized sex-specific and multidisciplinary pain treatment. PMID- 26542236 TI - Associations between Cerebral Embolism and Carotid Intraplaque Hemorrhage during Protected Carotid Artery Stenting. AB - BACKGROUND AND PURPOSE: Carotid artery stent placement in patients with intraplaque hemorrhage remains controversial because of the incidence of cerebral embolism after the procedure. The purpose of this study is to determine if intraplaque hemorrhage is a significant risk factor for cerebral embolism during carotid artery stent placement. MATERIALS AND METHODS: This prospective study assessed 94 consecutive patients with severe carotid stenosis. These patients underwent preprocedural carotid MR imaging and postprocedural DWI after carotid artery stent placement. Intraplaque hemorrhage was defined as the presence of high signal intensity within the carotid plaque that was >200% of the signal from the adjacent muscle on MPRAGE. We then analyzed the incidence of postprocedural ipsilateral ischemic events on DWI and primary outcomes within 30 days of carotid artery stent placement. RESULTS: Forty-three patients (45.7%) had intraplaque hemorrhage on an MPRAGE image. There was no significant difference in the incidence of postprocedural ipsilateral ischemic events and primary outcomes between the intraplaque hemorrhage and non-intraplaque hemorrhage group. However, postprocedural ipsilateral ischemic events were more frequently observed in the symptomatic group (17/41 [41.5%]) than in the asymptomatic group (8/53 [15.1%]; P = .005). CONCLUSIONS: Intraplaque hemorrhage was not a significant risk factor for cerebral embolism during carotid artery stent placement in patients with severe carotid stenosis. Symptomatic patients should receive more careful treatment during carotid artery stent placement because of the higher risk of postprocedural ipsilateral ischemic events. PMID- 26542235 TI - MR Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus. AB - BACKGROUND AND PURPOSE: Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex matched cognitively healthy individuals. MATERIALS AND METHODS: MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20). CONCLUSIONS: This study demonstrates increased brain stiffness in patients with normal pressure hydrocephalus compared with age- and sex-matched healthy controls; these findings should motivate future studies investigating the use of MR elastography for this condition and the efficacy of shunt therapy. PMID- 26542238 TI - Radiation Doses in Patient Eye Lenses during Interventional Neuroradiology Procedures. AB - BACKGROUND AND PURPOSE: Eye lenses are among the most sensitive organs to x-ray radiation and may be considered at risk during neurointerventional radiology procedures. The threshold dose to produce eye lens opacities has been recently reduced to 500 mGy by the International Commission on Radiologic Protection. In this article, the authors investigated the radiation doses delivered to patients' eyes during interventional neuroradiology procedures at a university hospital. MATERIALS AND METHODS: Small optically stimulated luminescence dosimeters were located over patients' eyes during 5 diagnostic and 31 therapeutic procedures performed in a biplane x-ray system. Phantom measurements were also made to determine the level of radiation to the eye during imaging runs with conebeam CT. RESULTS: The left eye (located toward the lateral C-arm x-ray source) received a 4.5 times greater dose than the right one. The average dose during embolization in the left eye was 300 mGy, with a maximum of 2000 mGy in a single procedure. The patient who received this maximum eye dose needed 6 embolization procedures to treat his high-volume AVM. If one took into account those 6 embolizations, the eye dose could be 2-fold. Sixteen percent of the embolizations resulted in eye doses of >500 mGy. CONCLUSIONS: A relevant fraction of patients received eye doses exceeding the threshold of 500 mGy. A careful optimization of the procedures and follow-up of these patients to evaluate potential lens opacities should be considered. PMID- 26542237 TI - GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T. AB - BACKGROUND AND PURPOSE: Complex motor stereotypies are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies) as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiologic basis for these movements is unknown but is thought to involve cortical-striatal-thalamo-cortical pathways. To further clarify potential neurochemical alterations, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetylaspartate, and choline levels were measured in 4 frontostriatal regions by using (1)H MRS at 7T. MATERIALS AND METHODS: A total of 18 children with primary complex motor stereotypies and 24 typically developing controls, ages 5 10 years, completed MR spectroscopy at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex, and striatum were obtained, and metabolites were quantified with respect to Cr by using LCModel. RESULTS: The 7T scan was well tolerated by all the participants. Compared with the controls, children with complex motor stereotypies had lower levels of GABA in the anterior cingulate cortex (GABA/Cr, P = .049; GABA/Glu, P = .051) and striatum (GABA/Cr, P = .028; GABA/Glu, P = .0037) but not the dorsolateral prefrontal cortex or the premotor cortex. Glutamate, glutamine, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the complex motor stereotypies group, reduced GABA to Cr in the anterior cingulate cortex was significantly associated with greater severity of motor stereotypies (r = -0.59, P = .021). CONCLUSIONS: These results indicate possible GABAergic dysfunction within corticostriatal pathways in children with primary complex motor stereotypies. PMID- 26542239 TI - Phenolic constituents of the Bangladeshi medicinal plant Pothos scandens and their anti-estrogenic, hyaluronidase inhibition, and histamine release inhibitory activities. AB - Extracts from the stem and roots of the Bangladeshi medicinal plant Pothos scandens L. (Araceae) were isolated, and three hemiterpene glucoside aromatic esters, pothobanosides A (1), B (2), and C (3), and a phenylisobutanoid, pothobanol (4), along with 14 known compounds, were characterized. The isolates were tested for their estrogenic/anti-estrogenic activity using the estrogen responsive human breast cancer cell lines MCF-7 and T47D, and syringoyl derivatives (2, 3, and canthoside B) showed strong inhibitory activity against both cell lines. Their less oxygenated analogs (1, and markhamioside F) were almost inactive. The isolates were also evaluated for hyaluronidase and histamine release inhibitory activities, and pothobanoside A (1) showed significant hyaluronidase inhibitory activity among the isolated compounds, which was similar to that of the positive control rosmarinic acid. Because hyaluronidase produces an angiogenic response that has been implicated in tumor invasiveness and metastasis, 1 could be valuable as an anti-tumor compound with a different mechanism of action from related compounds (2, 3). Pothobanoside C (3) and pothobanol (4) were also found to inhibit histamine release to a similar degree to the positive control epigallocatechin 3-O-(3"-O-methyl)-gallate. The histamine release inhibitory potency of these isolates may support the traditional uses of this plant in folk medicine. PMID- 26542240 TI - Protocol for a systematic review of quantitative burn wound microbiology in the management of burns patients. AB - BACKGROUND: Sepsis from burn injuries can result from colonisation of burn wounds, especially in large surface area burns. Reducing bacterial infection will reduce morbidity and mortality, and mortality for severe burns can be as high as 15 %. There are various quantitative and semi-quantitative techniques to monitor bacterial load on wounds. In the UK, burn wounds are typically monitored for the presence or absence of bacteria through the collection and culture of swabs, but no absolute count is obtained. Quantitative burn wound culture provides a measure of bacterial count and is gaining increased popularity in some countries. It is however more resource intensive, and evidence for its utility appears to be inconsistent. This systematic review therefore aims to assess the evidence on the utility and reliability of different quantitative microbiology techniques in terms of diagnosing or predicting clinical outcomes. METHODS/DESIGN: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Bibliographic databases and ongoing trial registers will be searched and conference abstracts screened. Studies will be eligible if they are prospective studies or systematic reviews of burn patients (any age) for whom quantitative microbiology has been performed, whether it is compared to another method. Quality assessment will be based on quality assessment tools for diagnostic and prognostic studies and tailored to the review as necessary. Synthesis is likely to be primarily narrative, but meta analysis may be considered where clinical and methodological homogeneity exists. DISCUSSION: Given the increasing use of quantitative methods, this is a timely systematic review, which will attempt to clarify the evidence base. As far as the authors are aware, it will be the first to address this topic. TRIAL REGISTRATION: PROSPERO, CRD42015023903. PMID- 26542241 TI - Programmed death 1 blockade, an Achilles heel for MMR-deficient tumors? AB - Program death receptor-1 (PD-1) is upregulated in many tumors and in tumor microenvironment, and PD-1 blockade has led to remarkable immune-based anti-tumor responses in across many tumor types. Pembrolizumab, an anti-programmed death 1 checkpoint inhibitor, resulted in a high rate of immune response in 41 patients with previously treated mismatch repair (MMR)-deficient tumor including colorectal cancer but not in MMR-stable tumor with expectant toxicities. Both immune-based progression-free and overall survival are quite promising and correlate with high mutation loads in the tumor. MMR-deficient tumors made up not an insignificant proportion of GI and GU cancers and are found mostly in younger patients who had better prognosis than MMR-stable tumors. However, MMR-deficient tumors do not respond to cytotoxic chemotherapy as these agents may require intact DNA mismatch repair to be effective. MMR deficiency occurred as a result of mutations in defined DNA repair complex mutations or epigenetics modifications and gene upstream of DNA repair complex. PD-1 blockade represents our first successful shot at one of the Achilles heels of this MMR-deficient tumor Goliath. Only coordinated attack on all of its Achilles heels and healing mechanisms can this tumor Goliath be brought down to its knees. PMID- 26542242 TI - The role of mutations and overexpression of the fibroblast growth factor receptor 3 in bladder cancer. AB - Bladder cancer (BC) is the seventh most common cancer worldwide. Throughout the last decade, several studies demonstrated that the fibroblast growth factor (FGF) signalling is altered in a significant proportion of patients with BC. FGF receptor (FGFR) 3 may thus serve as a promising biomarker for BC. Mutations of this gene are prevalent in BC (e.g., found in 74% of non-invasive papillary tumours), suggesting that FGFR3 status is an important event in BC. The aim of this review was to overview the outcomes of different mutations in FGFR3 receptor in the context of BC. We first described FGFR3 receptor and continue with mutations of FGFR3 gene, including activating mutations and overexpression of this gene. Finally, we addressed the clinical relevance of mutated FGFR3 gene. PMID- 26542244 TI - Statin-centered treatment of dyslipidemia. New evidence-based paradigm, or only part of the evidence? PMID- 26542243 TI - The relation between insulin resistance and lung function: a cross sectional study. AB - BACKGROUND: Impaired lung function and insulin resistance have been associated and thereby have also been indicated to be powerful predictors of cardiovascular mortality. Therefore, the co-existence of insulin resistance and impaired lung function accompanied with cardiovascular risk factors should induce cardiovascular mortality even in patients without known respiratory disease in a cumulative pattern. It could be useful to determine the lung function of patients with insulin resistance in order to decrease cardiovascular mortality by means of taking measures that minimize the risk of decline in lung function. However, no prior studies have been done on association between insulin resistance and lung function in adults in Turkey. We aimed to determine if insulin resistance plays a detrimental role in lung function in outpatients admitted to internal medicine clinics in adults from Turkey. METHODS: A total of 171 outpatients (mean +/- SD) age: 43.1 +/- 11.9) years) admitted to internal medicine clinics were included in this single-center cross-sectional study, and were divided into patients with (n = 63, mean +/- SD) age: 43.2 +/- 12.5) years, 83.5 % female) or without (n = 108, mean +/- SD) age: 43.0 +/- 11.6) years, 93.5 % female) insulin resistance. All patients were non-smokers. Data on gender, age, anthropometrics, blood pressure, blood biochemistry, metabolic syndrome (MetS), and lung function tests were collected in each patient. Correlates of insulin resistance were determined via logistic regression analysis. RESULTS: Insulin resistance was present in 36.8 % of patients. Logistic regression analysis revealed an increase in the likelihood of having insulin resistance of 1.07 times with every 1-point increase in waist circumference, 1.01 times with every 1-point increase in triglycerides, 0.93 times with every 1-point decrease in HDL (high density lipoprotein) cholesterol, and 0.86 times with every 1-point decrease in percentage of FEV1/FVC pre (FEV1%pre: Forced expiratory volume in the first second of expiration for predicted values; FVC%pre.: Forced vital capacity for predicted values). CONCLUSIONS: Insulin resistance should also be considered amongst the contributing factors for decline in lung function. PMID- 26542245 TI - Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities. AB - BACKGROUND: In humans, Mammalian Target of Rapamycin (MTOR) encodes a 300 kDa serine/ threonine protein kinase that is ubiquitously expressed, particularly at high levels in brain. MTOR functions as an integrator of multiple cellular processes, and in so doing either directly or indirectly regulates the phosphorylation of at least 800 proteins. While somatic MTOR mutations have been recognized in tumors for many years, and more recently in hemimegalencephaly, germline MTOR mutations have rarely been described. CASE PRESENTATION: We report the successful application of family-trio Diagnostic Exome Sequencing (DES) to identify the underlying molecular etiology in two brothers with multiple neurological and developmental lesions, and for whom previous testing was non diagnostic. The affected brothers, who were 6 and 23 years of age at the time of DES, presented symptoms including but not limited to mild Autism Spectrum Disorder (ASD), megalencephaly, gross motor skill delay, cryptorchidism and bilateral iris coloboma. Importantly, we determined that each affected brother harbored the MTOR missense alteration p.E1799K (c.5395G>A). This exact variant has been previously identified in multiple independent human somatic cancer samples and has been shown to result in increased MTOR activation. Further, recent independent reports describe two unrelated families in whom p.E1799K co segregated with megalencephaly and intellectual disability (ID); in both cases, p.E1799K was shown to have originated due to germline mosaicism. In the case of the family reported herein, the absence of p.E1799K in genomic DNA extracted from the blood of either parent suggests that this alteration most likely arose due to gonadal mosaicism. Further, the p.E1799K variant exerts its effect by a gain-of function (GOF), autosomal dominant mechanism. CONCLUSION: Herein, we describe the use of DES to uncover an activating MTOR missense alteration of gonadal mosaic origin that is likely to be the causative mutation in two brothers who present multiple neurological and developmental abnormalities. Our report brings the total number of families who harbor MTOR p.E1799K in association with megalencephaly and ID to three. In each case, evidence suggests that p.E1799K arose in the affected individuals due to gonadal mosaicism. Thus, MTOR p.E1799K can now be classified as a pathogenic GOF mutation that causes megalencephaly and cognitive impairment in humans. PMID- 26542246 TI - Body mass index is associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men: a retrospective cohort study and meta-analysis. AB - BACKGROUND: The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men. METHODS: Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5 +/- 27.0 months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations. RESULTS: Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95 % confidence interval (CI) 1.023-1.322, P = 0.021) and pathological Gleason score (OR 1.220, 95 % CI 1.056-1.410, P = 0.007) in multivariate analysis. BCR was detected in 48 patients (22.7 %). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95 % CI 1.029-1.273, P = 0.013) and prostate-specific antigen (HR 1.659, 95 % CI 1.102-2.497, P = 0.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random effects approach, a 5 kg/m(2) increase in BMI was correlated with 28 % higher risk of BCR (HR 1.22, 95 % CI 0.86-1.72) without statistical significance. CONCLUSIONS: The present study suggested that higher BMI was an independent risk factor for a higher Gleason score, as well as an independent predictor of BCR after radical prostatectomy in Chinese patients. Meta-analysis of Asian studies also indicated that obese patients, although without statistical significance, might be more likely to suffer from BCR. PMID- 26542247 TI - Differential effects of lacosamide, phenytoin and topiramate on peripheral nerve excitability: An ex vivo electrophysiological study. AB - BACKGROUND: Antiepileptic drugs (AEDs) are mainly used to control cortical hyperexcitability. Some of them (e.g. phenytoin (PHT) and topiramate (TPM)) have also effects on the peripheral nervous system (PNS). Lacosamide (LCM) is a novel AED that stabilizes hyperexcitable neuronal membranes by selectively enhancing the slow inactivation of voltage-gated sodium channels (VGSCs). Although the mechanism of action of LCM is fairly well understood, there are no in vitro data available regarding any possible PNS effects of LCM. OBJECTIVE: To investigate, in vitro, the effects of LCM on peripheral nerve excitability in comparison with PHT and TPM, two AEDs that act, in part, by stabilizing the fast inactivation state of VGSCs. METHODS: Experiments were conducted on the isolated sciatic nerve of the adult rat using standard electrophysiological methods. The effects of LCM on the amplitude and latency of the evoked compound action potential (CAP) during a 48h period of drug exposure were recorded and compared with the effects of PHT and TPM. RESULTS: LCM produced inhibitory effects on CAP at concentrations significantly higher than the therapeutic levels (>25MUg/ml). At these concentrations (62.57-125.15MUg/ml), an acute and immediate increment of the latency and decrement of the amplitude of the CAP were observed. In contrast to LCM, PHT caused an acute decrement in the amplitude as well as an increment in the latency of the CAP even at subtherapeutic levels (5MUg/ml). With regard to TPM, the amplitude of the CAP was not affected at the supratherapeutic concentrations but at the therapeutic concentration of 33.94MUg/ml a reduced decrement of the CAP amplitude compared to the controls was observed. CONCLUSIONS: LCM, PHT and TPM exert differential effects on peripheral nerve excitability. PHT inhibited the sciatic nerve CAP even at subtherapeutic levels whereas LCM was safe within the therapeutic concentration range. TPM did not affect the CAP amplitude even at high supratherapeutic concentrations whereas in the therapeutic range a neuroprotective effect was observed. Possible underlying mechanisms and the clinical implications of these findings are discussed. PMID- 26542249 TI - First prospective clinical trial in adult HLH. PMID- 26542248 TI - The role of HO-1 in protection against lead-induced neurotoxicity. AB - Lead is a pervasive and persistent environmental pollutant that exerts deleterious effects on all living organisms and continues to threaten public health on a global scale. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis and protect cells from oxidative stress. This study was designed to explore the role of HO-1 in protection against lead neurotoxicity and the signaling pathways involved. Lead acetate (PbAc) exposure resulted in increased HO-1 expression in primary rat hippocampal neurons and SH-SY5Y cells. PbAc induced intracellular reactive oxygen species (ROS) also increased, and cell viability decreased in SH-SY5Y cells. We further demonstrated that HO-1 could be induced by PbAc through the P38, ERK1/2, and PI3K/AKT signaling pathways in a ROS dependent manner and through the JNK pathway in a ROS-independent manner. Further investigation revealed that HO-1 overexpression significantly restrained cell apoptosis and ROS production induced by PbAc in SH-SY5Y cells. Moreover, HO-1 knockdown aggravated PbAc-induced cell apoptosis and ROS production. Our results indicated that HO-1 was a novel protective factor that could efficiently inhibit PbAc-induced oxidative stress and cell death in the nervous system, thereby providing the potential therapeutic strategies for the prevention and treatment of lead-related diseases. PMID- 26542250 TI - Cell-specific PD-L1 expression in DLBCL. PMID- 26542251 TI - Ibrutinib in CLL: 2 sides of the same coin. PMID- 26542252 TI - Platelets promote pulmonary pull of polys. PMID- 26542253 TI - Inflammation is key to hemophilic arthropathy. PMID- 26542254 TI - Animal models of VT: to change or not to change? PMID- 26542255 TI - Gendercide and femineglect. AB - Gendercide and femineglect (the deliberate neglect of females vis-a-vis health, education, etc.) is rampant, especially in Asia. This paper reviews gendercide, the selective abortion of female foetuses based solely on gender, and femineglect, along with the inevitable and potentially catastrophic demographic consequences. PMID- 26542256 TI - Seasonal inconstancy of human sex ratio at birth. AB - A large body of literature describes relationships between the sex ratio at birth and modifying factors. The relationships that display seasonal fluctuations are hypothesized to reflect causal impact of periconceptional and later intrauterine effects. This short review summarizes the results of studies that investigated internal and external influences on the seasonal pattern of human sex ratio at birth. PMID- 26542257 TI - Elevated DMBT1 levels in neonatal gastrointestinal diseases. AB - Deleted in malignant brain tumor 1 (DMBT1) is involved in innate immunity and epithelial differentiation. Previous studies in adults indicated a strong intestinal expression of DMBT1 and an important role in inflammatory bowel diseases. Here, we analyzed the DMBT1 expression in the fetal gastrointestinal system depending on gestational age and in patients with necrotizing enterocolitis (NEC), volvulus, intestinal perforation (IP), or herniation, representing typical diseases of preterm and term infants. We used immunohistochemistry and RNA in situ hybridization to detect DMBT1 protein and mRNA in fetal tissues, supplemented by postmortem analysis of DMBT1 expression in died newborns and analysis of surgically removed tissues. DMBT1 expression is detectable in the early developmental stages of the gastrointestinal system. In NEC, volvulus, IP, or herniation, characterized by high systemic inflammatory responses, DMBT1 expression is strongly increased. High DMBT1 expression was also found in the bile ducts of older infants with sepsis or cholestasis. The study shows that DMBT1 expression is observed in the developing gastrointestinal system and up-regulated in infants with NEC, volvulus, IP, and herniation. DMBT1 may play a role in epithelial differentiation and local innate immunity during neonatal inflammatory bowel processes. PMID- 26542258 TI - Good people who try their best can have problems: recognition of human factors and how to minimise error. AB - Human error is as old as humanity itself and is an appreciable cause of mistakes by both organisations and people. Much of the work related to human factors in causing error has originated from aviation where mistakes can be catastrophic not only for those who contribute to the error, but for passengers as well. The role of human error in medical and surgical incidents, which are often multifactorial, is becoming better understood, and includes both organisational issues (by the employer) and potential human factors (at a personal level). Mistakes as a result of individual human factors and surgical teams should be better recognised and emphasised. Attitudes and acceptance of preoperative briefing has improved since the introduction of the World Health Organization (WHO) surgical checklist. However, this does not address limitations or other safety concerns that are related to performance, such as stress and fatigue, emotional state, hunger, awareness of what is going on situational awareness, and other factors that could potentially lead to error. Here we attempt to raise awareness of these human factors, and highlight how they can lead to error, and how they can be minimised in our day-to-day practice. Can hospitals move from being "high risk industries" to "high reliability organisations"? PMID- 26542259 TI - Extended role of Thudichum's nasal speculum for maxillomandibular segmental osteotomy: a new technique. PMID- 26542260 TI - Molecular typing of the actin gene of Trichomonas vaginalis isolates by PCR-RFLP in Iran. AB - Trichomonas vaginalis is a human urogenital pathogen that causes trichomoniasis, the most common nonviral, parasitic sexually transmitted infection in the world. At present, little is known regarding the degree of strain variability of T. vaginalis. A classification method for T. vaginalis strains would be a useful tool in the study of the epidemiology, drug resistance, pathogenesis and transmission of T. vaginalis. Eight different types of actin genes have been identified by PCR-RFLP in T. vaginalis; the purpose of this study is to determine the genotypes of this parasite in Karaj city, Iran. Forty-five clinical T. vaginalis isolates from vaginal secretions and urine sediment were collected from Karaj city from 2012 through 2014. DNA was extracted and the actin gene was amplified by nested-PCR; all samples were positive. To determine the genetic differences, sequencing on seven samples was conducted. Then, all PCR products were digested with HindII, MseI, and RsaI restriction enzymes. Of 45 isolates, 23 samples (51.1%) were of actin genotype G, 11 samples (24.4%) of genotype E, six samples (13.3%) of genotype H, three samples (6.6%) of genotype I, and two samples (4.4%) were mixed genotypes of G and E. Genetic diversity of T. vaginalis isolates is notable. The actin genotype G may be the dominant genotype in Karaj city, Iran. PMID- 26542261 TI - A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance. AB - The helminth parasite Fasciola hepatica causes fascioliasis in human and domestic ruminants. Economic losses due to this infection are estimated in U$S 2000-3000 million yearly. The most common method of control is the use of anthelmintic drugs. However, there is an increased concern about the growing appearance of F. hepatica resistance to Triclabendazole (TCBZ), an anthelmintic with activity over adult and young flukes. F. hepatica has eight Glutathione S-Transferase (GST) isozymes, which are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione. In the present work we identified and characterized the GST mu gene isolated from the TCBZ-susceptible and TCBZ-resistant F. hepatica strains. Total RNA was transcribed into cDNA by reverse transcription and a 657 bp amplicon corresponding to the GST mu gene was obtained. The comparative genetic analysis of the GST mu gene of the TCBZ susceptible strain (Cullompton) and TCBZ resistant strain (Sligo) showed three nucleotide changes and one amino acid change at position 143 in the GST mu isozyme of the TCBZ-resistant strain. These results have potential relevance as they contribute better understand the mechanisms that generate resistance to anthelmintics. PMID- 26542262 TI - Interarm differences in systolic blood pressure and the risk of dementia and subclinical brain injury. AB - INTRODUCTION: This study examined whether interarm differences in systolic blood pressure (IDSBP) >=10 mm Hg were associated with the risk of incident dementia and subclinical brain injury. METHODS: Between 1992 and 1998, 2063 participants of the Framingham Heart Study underwent assessment of IDSBP with results related to the 10-year risk of incident dementia including clinically characterized Alzheimer's disease. Secondary outcomes included markers of subclinical brain injury on magnetic resonance imaging. RESULTS: High IDSBP were associated with a greater risk of incident dementia (hazard ratio [HR] 1.92; 95% confidence interval [CI], 1.09-3.40) and Alzheimer's disease (HR, 2.32; 95% CI, 1.29-4.18), but only in those who carried an apolipoprotein E (APOE) epsilon4 allele. IDSBP also predicted lower total brain volumes and more prevalent silent brain infarcts in those who were APOE epsilon4 positive. DISCUSSION: High IDSBP were associated with an increased risk of dementia, including clinical Alzheimer's disease, and subclinical brain injury in those who were APOE epsilon4 positive. PMID- 26542263 TI - Heat stress acutely activates insulin-independent glucose transport and 5'-AMP activated protein kinase prior to an increase in HSP72 protein in rat skeletal muscle. AB - Heat stress (HS) stimulates heat shock protein (HSP) 72 mRNA expression, and the period after an increase in HSP72 protein is characterized by enhanced glucose metabolism in skeletal muscle. We have hypothesized that, prior to an increase in the level of HSP72 protein, HS activates glucose metabolism by acutely stimulating 5'-AMP-activated protein kinase (AMPK). Rat epitrochlearis muscle was isolated and incubated either with or without HS (42 degrees C) for 10 and 30 min. HS for 30 min led to an increase in the level of Hspa1a and Hspa1b mRNA but did not change the amount of HSP72 protein. However, HS for both 10 and 30 min led to a significant increase in the rate of 3-O-methyl-d-glucose (3MG) transport, and the stimulatory effect of 3MG transport was completely blocked by cytochalasin B. HS-stimulated 3MG transport was also inhibited by dorsomorphin but not by wortmannin. HS led to a decrease in the concentration of ATP, phosphocreatine, and glycogen, to an increase in the level of phosphorylation of AMPKalpha Thr(172), and to an increase in the activity of both AMPKalpha1 and AMPKalpha2. HS did not affect the phosphorylation status of insulin receptor signaling or Ca(2+)/calmodulin-dependent protein kinase II. These results suggest that HS acts as a rapid stimulator of insulin-independent glucose transport, at least in part by stimulating AMPK via decreased energy status. Although further research is warranted, heat treatment of skeletal muscle might be a promising method to promote glucose metabolism acutely. PMID- 26542264 TI - Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study. AB - Obesity is associated with differences in satiety, gastric emptying (GE), gastric volume, and psychological traits. Exenatide, a short-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is associated with variable weight loss. We compared the effects of exenatide, 5 MUg, and placebo SQ, twice daily for 30 days on GE of solids and liquids (scintigraphy), satiety (ad libitum buffet meal), satiation (nutrient drink test, maximum tolerated volume [MTV]), and weight loss in 20 participants with documented accelerated GE of solids (T1/2 < 90 min). Exenatide delayed GE of solids (T1/2 [Delta] 86 min relative to placebo, P < 0.001) and reduced calorie intake at buffet meal ([Delta] 129 kcal compared to placebo). Median weight loss was -0.95 kg (IQR -0.7 to -2.1) for exenatide and -0.55 kg (0.3 to -2.1) for placebo (P = 0.23); 80% of exenatide group had documented reduction in weight. In the exenatide treatment group, there was an inverse correlation between gastric emptying T1/2 and MTV (R = -0.548, P = 0.089). The univariate association of weight change with posttreatment MTV was borderline (Rs = 0.43, P = 0.06); in the multiple regression model, posttreatment MTV was associated with weight change (P = 0.047). The effect of the short-acting GLP-1 receptor agonist, exenatide, on GE is associated with the change in food intake, and the latter impacts weight loss in response to exenatide treatment. PMID- 26542266 TI - Editorial Comment. PMID- 26542267 TI - Editorial Comment. PMID- 26542268 TI - Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. AB - BACKGROUND: 5-Fluorouracil (5-FU) is a chemotherapy used in colorectal, head and neck (H&N) and other cancers. Dose adjustment is based on body surface area (BSA) but wide variations occur. Pharmacokinetic (PK) dosing is suggested to bring plasma levels into the therapeutic range to promote fewer side effects and better patient outcomes. We investigated the clinical effectiveness and cost effectiveness of the My5-FU assay for PK dose adjustment to 5-FU therapy. OBJECTIVES: To systematically review the evidence on the accuracy of the My5-FU assay compared with gold standard methods [high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS)]; the effectiveness of My5-FU PK dosing compared with BSA; the effectiveness of HPLC and/or LC-MS compared with BSA; the generalisability of published My5-FU and PK studies; costs of using My5-FU; to develop a cost-effectiveness model. DATA SOURCES: We searched MEDLINE, EMBASE, Science Citation Index and other databases between January and April 2014. METHODS: Two reviewers independently screened titles and abstracts with arbitration and consensus agreement. We undertook quality assessment. We reconstructed Kaplan-Meier plots for progression-free survival (PFS) and overall survival (OS) for comparison of BSA and PK dosing. We developed a Markov model to compare My5-FU with BSA dosing which modelled PFS, OS and adverse events, using a 2-week cycle over a 20 year time horizon with a 3.5% discount rate. Health impacts were evaluated from the patient perspective, while costs were evaluated from the NHS and Personal Social Services perspective. RESULTS: A total of 8341 records were identified through electronic searches and 35 and 54 studies were included in the clinical effectiveness and cost-effectiveness reviews respectively. There was a high apparent correlation between My5-FU, HPLC and LC MS/mass spectrometer but upper and lower limits of agreement were -18% to 30%. Median OS were estimated as 19.6 [95% confidence interval (CI) 17.0 to 21.0] months for PK versus 14.6 (95% CI 14.1 to 15.3) months for BSA for 5-FU+folinic acid (FA); and 27.4 (95% CI 23.2 to 38.8) months for PK versus 20.6 (95% CI 18.4 to 22.9) months for BSA for FOLFOX6 in metastatic colorectal cancer (mCRC). PK versus BSA studies were generalisable to the relevant populations. We developed cost-effectiveness models for mCRC and H&N cancer. The base case assumed a cost per My5-FU assay of L 61.03. For mCRC for 12 cycles of a oxaliplatin in combination with 5-fluorouracil and FA (FOLFOX) regimen, there was a quality adjusted life-year (QALY) gain of 0.599 with an incremental cost-effectiveness ratio of L 4148 per QALY. Probabilistic and scenario analyses gave similar results. The cost-effectiveness acceptability curve showed My5-FU to be 100% cost effective at a threshold of L 20,000 per QALY. For H&N cancer, again, given caveats about the poor evidence base, we also estimated that My5-FU is likely to be cost-effective at a threshold of L 20,000 per QALY. LIMITATIONS: Quality and quantity of evidence were very weak for PK versus BSA dosing for all cancers with no randomised controlled trials (RCTs) using current regimens. For H&N cancer, two studies of regimens no longer in use were identified. CONCLUSIONS: Using a linked evidence approach, My5-FU appears to be cost-effective at a willingness to pay of L 20,000 per QALY for both mCRC and H&N cancer. Considerable uncertainties remain about evidence quality and practical implementation. RCTs are needed of PK versus BSA dosing in relevant cancers. PMID- 26542269 TI - Entropy-Driven 1,2-Type Friedel-Crafts Reaction of Phenols with N-tert Butoxycarbonyl Aldimines. AB - Differential activation entropy (DeltaDeltaS(?)) is revisited as an important parameter that governs catalytic stereodiscrimination processes by investigating temperature effects on the basis of the Eyring theory. However, correlating the DeltaDeltaS(?) effect and the molecular structure of the asymmetric catalyst is still an underdeveloped area. Efforts to identify factors (including catalyst structure, reactants, and reaction conditions) that contribute to the attainment of large DeltaDeltaS(?) values for enantioselective 1,2-type Friedel-Crafts reactions of phenols with N-tert-butoxycarbonyl aldimines catalyzed by conformationally flexible guanidine bisthioureas are described. First, we uncover an interesting property of the DeltaDeltaS(?)-driven stereodiscrimination process: maximum enantioselectivity is obtained at around room temperature. Second, a plausible transition-state model accounting for the characteristic DeltaDeltaS(?) effect and the structural dynamics of the conformationally flexible organocatalyst in the stereodiscrimination process is discussed. PMID- 26542270 TI - Keep your mind off negative things: coping with long-term effects of acute myeloid leukemia (AML). AB - PURPOSE OF STUDY: Acute myeloid leukemia (AML) is characterized by sudden onset, intensive treatment, a poor prognosis, and significant relapse risk. Quality of life (QOL) and well-being among AML survivors have been extensively studied during the 6 months of active treatment. However, it is not clear what survivors experience after active treatment. The purpose of our study was to explore how AML survivors describe their longer-term physical and psychosocial well-being and how they cope with these challenges. METHODS: We conducted a prospective qualitative study and interviewed 19 adult participants (11 had completed treatment, 8 were receiving maintenance chemotherapy). Data were collected using semi-structured interviews that were audio-recorded and transcribed verbatim. The grounded theory approach was used for data analysis. RESULTS: A marked improvement in physical health was reported; however, psychosocial well-being was compromised by enduring emotional distress. A range of emotion- and problem focused coping strategies were reported. Keeping one's mind off negative things through engaging in formal work or informal activities and seeking control were the two most commonly used coping strategies. Seeking social support for reassurance was also common. Problem-focused strategies were frequently described by the ongoing treatment group to manage treatment side effects. CONCLUSION: Although physical symptoms improved after completion of treatment, psychosocial distress persisted over longer period of time. In addition, essential needs of AML survivors shifted across survivorship as psychological burden gradually displaced physical concerns. The integral role of coping mechanisms in the adaptation process suggests a need for effective and ongoing psychological interventions. PMID- 26542271 TI - Effects of a physical therapy program combined with manual lymphatic drainage on shoulder function, quality of life, lymphedema incidence, and pain in breast cancer patients with axillary web syndrome following axillary dissection. AB - PURPOSE: The aim of this study was to evaluate the effects of physical therapy (PT) combined with manual lymphatic drainage (MLD) on shoulder function, pain, lymphedema, visible cords, and quality of life (QOL) in breast cancer patients with axillary web syndrome (AWS). METHODS: In this prospective, randomized trial, 41 breast cancer patients with visible and palpable cords on the arm and axilla and a numeric rating scale (NRS) pain score of >3 were randomly assigned to PT (3 times/week for 4 weeks; n = 20) and PT combined with MLD (5 times/week for 4 weeks; PTMLD; n = 21) groups. MLD was performed by a physical therapist and the patients themselves during week 1 and weeks 2-4, respectively. Arm volume, shoulder function (muscular strength; active range of motion; and disabilities of the arm, shoulder, and hand [DASH]); QOL (European Organization for Research and Treatment of Cancer Core and Breast Cancer-Specific QOL questionnaires), and pain (NRS) were assessed at baseline and after 4 weeks of treatment. RESULTS: QOL including functional and symptom aspects, shoulder flexor strength, DASH, and NRS scores were significantly improved in both groups after the 4-week intervention (P < 0.05). NRS score and arm volume were significantly lower in the PTMLD group than in the PT group (P < 0.05). Lymphedema was observed in the PT (n = 6), but not PTMLD, group (P < 0.05). CONCLUSIONS: PT improves shoulder function, pain, and QOL in breast cancer patients with AWS and combined with MLD decreases arm lymphedema. PMID- 26542273 TI - Erratum to: Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study. PMID- 26542272 TI - Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial. AB - PURPOSE: Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors. Herein, we examine the effect of CBT-I, with and without A, on fatigue in cancer survivors. PATIENTS AND METHODS: This study was a four-arm factorial study with CBTI-I (yes/no) versus A (yes/no). It consisted of 96 cancer survivors (average age 56 years; 88 % female; 68 % breast cancer). Fatigue was assessed by the brief fatigue inventory (BFI) and the FACIT-Fatigue scale. The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A. RESULTS: Analyses adjusting for baseline differences showed that CBT-I improved fatigue as measured by two separate scales (BFI: P = 0.002, Std. error = 0.32, effect size (ES) = 0.46; FACIT-Fatigue: P < 0.001, Std. error = 1.74, ES = 0.64). Armodafinil alone did not show a statistically significant effect on fatigue levels (all Ps > 0.40) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue. CONCLUSIONS: CBT-I with and without armodafinil resulted in a clinically and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia. Armodafinil did not improve cancer-related fatigue (CRF) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and, if indicated, treated for insomnia as part of a comprehensive fatigue management program. PMID- 26542274 TI - Polypharmacy in the terminal stage of cancer. AB - PURPOSE: This study aims to determine the numbers of patients with advanced cancer receiving polypharmacy at the end of their lives and analyze differences in drug prescription at a general oncology ward and a dedicated palliative care ward. METHODS: A retrospective single-center cohort study at a university hospital with a large cancer center was conducted. The charts of 100 patients who had died because of advanced cancer were reviewed; data concerning sociodemographic variables and medications were collected at four predefined time points (9, 6, 3, 0 days before death). RESULTS: Nine days before death, polypharmacy was registered in 95 % of patients; they had prescriptions for 11 (9 13) different medications per day (median, IQR). Although this number dropped significantly, on the last day as many as 61 % of the patients were still taking more than 4 drugs (median 6.5, IQR 4-9). No significant difference was noted between the oncology ward and the palliative care ward. Polypharmacy was largely dependent on the patients' ECOG performance status as well as the type of ward, the number of days before death, and age. It was not influenced by gender, the duration of hospital stays, and the devices facilitating drug administration. The medications fulfilled the requirements of palliative care in the majority of patients; 90 % received treatment for pain and anxiety. Patients treated at the palliative ward received more opioids and psychoactive drugs while those at the oncology ward received more anti-cancer drugs and fluids. CONCLUSIONS: Polypharmacy still is a problem in the large majority of patients with terminal cancer. Further studies should be focused on the patients' quality of life, drug interactions, and adverse events. PMID- 26542275 TI - Impact of Geographic Region on Benefit of Approved Anticancer Drugs Evaluated in International Phase III Clinical Trials. AB - AIMS: International collaboration allows for enhanced accrual and more generalisable results of phase III randomised controlled trials (RCTs). The impact of geographic region on the outcomes of new anticancer agents is unclear. MATERIALS AND METHODS: International RCTs evaluating approved systemic therapy for advanced solid tumours that reported efficacy of new anticancer drugs based on geographic regions were eligible. Data for overall (OS) or progression-free survival (PFS) were pooled in a meta-analysis. The primary analysis was the comparison of developed versus developing countries. A meta-regression analysis explored the impact of differences in gross national income (GNI) per capita on the hazard ratio comparing developed and developing countries. Secondary analyses compared geographic regions irrespective of GNI. RESULTS: Of the 63 identified studies, 12 independent RCTs were eligible; five reported data for OS and nine for PFS. Improvements in overall survival were greater in developed as compared with developing countries (hazard ratio 0.82, 95% confidence interval 0.68-0.99, P = 0.04). This effect was seen only among studies of cytotoxic chemotherapy and not among those of targeted agents. No difference was seen for PFS (hazard ratio 0.93, 95% confidence interval 0.79-1.09, P = 0.36). Meta-regression showed a significant negative association between GNI per capita and overall survival, but a non-significant negative association with PFS (beta = -0.774, P = 0.05 and beta = -0.211, P = 0.29, respectively). No differences were observed in PFS between Asian and non-Asian countries or North America and Western Europe. CONCLUSION: Compared with patients from developing countries, those from developed countries derive greater improvement in overall survival from cytotoxic chemotherapy, but similar benefit from targeted drugs. PMID- 26542276 TI - Combatting the Myth of Neuropathology. PMID- 26542278 TI - Nanoencapsulated curcumin and praziquantel treatment reduces periductal fibrosis and attenuates bile canalicular abnormalities in Opisthorchis viverrini-infected hamsters. AB - This study investigated the effects of nanoencapsulated curcumin (NEC) and praziquantel (PZQ) treatment on the resolution of periductal fibrosis (PDF) and bile canalicular (BC) abnormalities in Opisthorchis viverrini infected hamsters. Chronic O. viverrini infection (OV) was initially treated with either PZQ (OP) and subsequently treated with NEC (OP+NEC), curcumin (OP+Cur) or unloaded carriers (OP+carrier) daily for one month. OP+NEC treatment reduced the PDF by suppression of fibrotic markers (hydroxyproline content, alpha-SMA, CTGF, fibronectin, collagen I and III), cytokines (TGF-beta and TNF-alpha) and TIMP-1, 2, 3 expression and upregulation of MMP-7, 13 genes. Higher activity of NEC in reducing fibrosis compared to curcumin was also demonstrated in in vitro studies. Moreover, OP+NEC also prevented BC abnormalities and upregulated several genes involved in bile acid metabolism. These results demonstrate that NEC and PZQ treatment reduces PDF and attenuates BC defect in experimental opisthorchiasis. From the Clinical Editor: Infection by Opisthorchis viverrini leads to liver fibrosis and affects population in SE Asia. Currently, praziquantel (PZQ) is the drug of choice but this drug has significant side effects. In this study, the authors combined curcumin (NEC) and praziquantel in a nanocarrier to test the anti-oxidative effect of curcumin in an animal model. The encouraging results may pave a way for better treatment in the future. PMID- 26542279 TI - Elevated preoperative plasma D-dimer level is a useful predictor of chemoresistance and poor disease outcome for serous ovarian cancer patients. AB - PURPOSE: To examine whether the elevated preoperative plasma D-dimer levels show correlation with chemoresistance and poor prognosis in serous ovarian cancer patients. METHODS: Preoperative plasma D-dimer levels were measured in 125 patients with primary serous ovarian cancer (SOC).The correlations of plasma D dimer levels with clinicopathological features, chemotherapeutic response, and survival outcome were further analyzed. Kaplan-Meier estimates were used to compute the survival functions and were compared using log-rank tests. Cox proportional-hazard regression analysis was used to evaluate the effects of D dimer on progression-free survival (PFS) and overall survival (OS), controlling for potential confounding factors. RESULTS: The median follow-up period was 49 (range 5-85) months. Elevated plasma D-dimer levels were positively associated with advanced FIGO stage (P = 0.010), residual tumor size (P = 0.017), the presence of malignant ascites (P = 0.028), increased serum CA125 level (P = 0.014), and neo-adjuvant chemotherapy (P = 0.008). The patients with elevated plasma D-dimer levels had significantly higher chemoresistance rates (56.41 %) compared to the normal plasma D-dimer levels (20.93 %). Additionally, it was found by the univariate analysis that elevated plasma D-dimer levels were closely related with a low 5-year PFS rate (28.21 vs 52.33 %, P = 0.002) and a poor 5 year OS (30.77 vs 63.95 %, P < 0.001). However, after adjustment for other factors, high plasma D-dimer levels were only closely correlated with a poor 5 year OS (HR 1.901, 95 % CI 1.021-3.540; P = 0.043). CONCLUSIONS: Elevated preoperative plasma D-dimer levels were associated with chemoresistance and poor disease outcome in serous ovarian cancer patients. Further validation of this easily available parameter as a promising prognostic biomarker for patients with SOC in prospective studies should be encouraged. PMID- 26542280 TI - Osilodrostat, a potent oral 11beta-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing's disease. AB - PURPOSE: In a 10-week proof-of-concept study (LINC 1), the potent oral 11beta hydroxylase inhibitor osilodrostat (LCI699) normalized urinary free cortisol (UFC) in 11/12 patients with Cushing's disease. The current 22-week study (LINC 2; NCT01331239) further evaluated osilodrostat in patients with Cushing's disease. METHODS: Phase II, open-label, prospective study of two patient cohorts. Follow-up cohort: 4/12 patients previously enrolled in LINC 1, offered re enrollment if baseline mean UFC was above ULN. Expansion cohort: 15 newly enrolled patients with baseline UFC > 1.5 * ULN. In the follow-up cohort, patients initiated osilodrostat twice daily at the penultimate efficacious/tolerable dose in LINC 1; dose was adjusted as needed. In the expansion cohort, osilodrostat was initiated at 4 mg/day (10 mg/day if baseline UFC > 3 * ULN), with dose escalated every 2 weeks to 10, 20, 40, and 60 mg/day until UFC <= ULN. Main efficacy endpoint was the proportion of responders (UFC <= ULN or >=50% decrease from baseline) at weeks 10 and 22. RESULTS: Overall response rate was 89.5% (n/N = 17/19) at 10 weeks and 78.9% (n/N = 15/19) at 22 weeks; at week 22, all responding patients had UFC <= ULN. The most common AEs observed during osilodrostat treatment were nausea, diarrhea, asthenia, and adrenal insufficiency (n = 6 for each). New or worsening hirsutism (n = 2) and/or acne (n = 3) were reported among four female patients, all of whom had increased testosterone levels. CONCLUSIONS: Osilodrostat treatment reduced UFC in all patients; 78.9% (n/N = 15/19) had normal UFC at week 22. Treatment with osilodrostat was generally well tolerated. PMID- 26542281 TI - Developmental Screening Among Children Born Preterm in a High-Risk Follow-Up Clinic. AB - OBJECTIVE: The psychometric properties of two formats of developmental screening tools that may be used in follow-up clinics providing primary care to children born preterm are presented. METHODS: 28 children born extremely preterm (<27 weeks) attending a high-risk clinic at the time of their 18-24 month visit were administered the Child Development Review, Brigance Early Head Start Screen II, and Bayley Scales of Infant and Toddler Development-Third Edition. RESULTS: Both screeners identified the majority of the sample as at-risk. The Brigance Screen II more accurately identified children at-risk compared with the Child Developmental Review (sensitivity: 1.00 and 0.44; specificity: 0.60 and 0.80; positive predictive value: 79% and 80%; negative predictive value: 100% and 44%, respectively). CONCLUSIONS: Screening assessments using direct skills assessment may be an efficient and effective method of identifying children with developmental delays, particularly high-frequency but lower severity difficulties, in high-risk follow-up care settings. PMID- 26542282 TI - Prevalence and predictors of anxiety and depression among esophageal cancer patients prior to surgery. AB - This study aims to establish the prevalence and predictors of anxiety and depression among esophageal cancer patients, post-diagnosis but prior to curatively intended surgery. This was a cross-sectional study using data from a hospital-based prospective cohort study, carried out at St Thomas' Hospital, London. Potential predictor variables were retrieved from medical charts and self report questionnaires. Anxiety and depression were measured prior to esophageal cancer surgery, using the Hospital Anxiety and Depression Scale. Prevalence of anxiety and depression was calculated using the established cutoff (scores >=8 on each subscale) indicating cases of 'possible-probable' anxiety or depression, and multivariable logistic regression analyses were performed to examine predictors of emotional distress. Among the 106 included patients, 36 (34%) scored above the cutoff (>=8) for anxiety and 24 (23%) for depression. Women were more likely to report anxiety than men (odds ratio 4.04, 95% confidence interval 1.45-11.16), and patients reporting limitations in their activity status had more than five times greater odds of reporting depression (odds ratio 6.07, 95% confidence interval 1.53-24.10). A substantial proportion of esophageal cancer patients report anxiety and/or depression prior to surgery, particularly women and those with limited activity status, which highlights a need for qualified emotional support. PMID- 26542283 TI - Haplotype divergence and multiple candidate genes at Rphq2, a partial resistance QTL of barley to Puccinia hordei. AB - KEY MESSAGE: Rphq2, a minor gene for partial resistance to Puccinia hordei , was physically mapped in a 188 kbp introgression with suppressed recombination between haplotypes of rphq2 and Rphq2 barley cultivars. ABSTRACT: Partial and non host resistances to rust fungi in barley (Hordeum vulgare) may be based on pathogen-associated molecular pattern (PAMP)-triggered immunity. Understanding partial resistance may help to understand non-host resistance, and vice versa. We constructed two non-gridded BAC libraries from cultivar Vada and line SusPtrit. Vada is immune to non-adapted Puccinia rust fungi, and partially resistant to P. hordei. SusPtrit is susceptible to several non-adapted rust fungi, and has been used for mapping QTLs for non-host and partial resistance. The BAC libraries help to identify genes determining the natural variation for partial and non-host resistances of barley to rust fungi. A major-effect QTL, Rphq2, for partial resistance to P. hordei was mapped in a complete Vada and an incomplete SusPtrit contig. The physical distance between the markers flanking Rphq2 was 195 Kbp in Vada and at least 226 Kbp in SusPtrit. This marker interval was predicted to contain 12 genes in either accession, of which only five genes were in common. The haplotypes represented by Vada and SusPtrit were found in 57 and 43%, respectively, of a 194 barley accessions panel. The lack of homology between the two haplotypes probably explains the suppression of recombination in the Rphq2 area and limit further genetic resolution in fine mapping. The possible candidate genes for Rphq2 encode peroxidases, kinases and a member of seven-in-absentia protein family. This result suggests that Rphq2 does not belong to the NB-LRR gene family and does not resemble any of the partial resistance genes cloned previously. PMID- 26542284 TI - Degradation of phenolic compounds by the lignocellulose deconstructing thermoacidophilic bacterium Alicyclobacillus Acidocaldarius. AB - Alicyclobacillus acidocaldarius, a thermoacidophilic bacterium, has a repertoire of thermo- and acid-stable enzymes that deconstruct lignocellulosic compounds. The work presented here describes the ability of A. acidocaldarius to reduce the concentration of the phenolic compounds: phenol, ferulic acid, rho-coumaric acid and sinapinic acid during growth conditions. The extent and rate of the removal of these compounds were significantly increased by the presence of micro-molar copper concentrations, suggesting activity by copper oxidases that have been identified in the genome of A. acidocaldarius. Substrate removal kinetics was first order for phenol, ferulic acid, rho-coumaric acid and sinapinic acid in the presence of 50 MUM copper sulfate. In addition, laccase enzyme assays of cellular protein fractions suggested significant activity on a lignin analog between the temperatures of 45 and 90 degrees C. This work shows the potential for A. acidocaldarius to degrade phenolic compounds, demonstrating potential relevance to biofuel production and other industrial processes. PMID- 26542285 TI - Adipocyte lipolysis and insulin resistance. AB - Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. PMID- 26542287 TI - Positional proteomics in the era of the human proteome project on the doorstep of precision medicine. AB - Proteolytic processing is a pervasive and irreversible post-translational modification that expands the protein universe by generating new proteoforms (protein isoforms). Unlike signal peptide or prodomain removal, protease generated proteoforms can rarely be predicted from gene sequences. Positional proteomic techniques that enrich for N- or C-terminal peptides from proteomes are indispensable for a comprehensive understanding of a protein's function in biological environments since protease cleavage frequently results in altered protein activity and localization. Proteases often process other proteases and protease inhibitors which perturbs proteolytic networks and potentiates the initial cleavage event to affect other molecular networks and cellular processes in physiological and pathological conditions. This review is aimed at researchers with a keen interest in state of the art systems level positional proteomic approaches that: (i) enable the study of complex protease-protease, protease inhibitor and protease-substrate crosstalk and networks; (ii) allow the identification of proteolytic signatures as candidate disease biomarkers; and (iii) are expected to fill the Human Proteome Project missing proteins gap. We predict that these methodologies will be an integral part of emerging precision medicine initiatives that aim to customize healthcare, converting reactive medicine into a personalized and proactive approach, improving clinical care and maximizing patient health and wellbeing, while decreasing health costs by eliminating ineffective therapies, trial-and-error prescribing, and adverse drug effects. Such initiatives require quantitative and functional proteome profiling and dynamic disease biomarkers in addition to current pharmacogenomics approaches. With proteases at the pathogenic center of many diseases, high throughput protein termini identification techniques such as TAILS (Terminal Amine Isotopic Labeling of Substrates) and COFRADIC (COmbined FRActional DIagonal Chromatography) will be fundamental for individual and comprehensive assessment of health and disease. PMID- 26542286 TI - Creatine biosynthesis and transport in health and disease. AB - Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as autosomal recessive (mutations affecting GATM [for glycine-amidinotransferase, mitochondrial]) and GAMT genes) or X-linked (SLC6A8 gene) traits. They have highlighted the role of creatine in brain functions altered in patients (global developmental delay, intellectual disability, behavioral disorders). Creatine modulates GABAergic and glutamatergic cerebral pathways, presynaptic CRTR (SLC6A8) ensuring re-uptake of synaptic creatine. Secondary creatine disorders, addressing other genes, have stressed the extraordinary imbrication of creatine metabolism with many other cellular pathways. This high dependence on multiple pathways supports creatine as a cellular sensor, to cell methylation and energy status. Creatine biosynthesis consumes 40% of methyl groups produced as S adenosylmethionine, and creatine uptake is controlled by AMP activated protein kinase, a ubiquitous sensor of energy depletion. Today, creatine is considered as a potential sensor of cell methylation and energy status, a neurotransmitter influencing key (GABAergic and glutamatergic) CNS neurotransmission, therapeutic agent with anaplerotic properties (towards creatine kinases [creatine-creatine phosphate cycle] and creatine neurotransmission), energetic and antioxidant compound (benefits in degenerative diseases through protection against energy depletion and oxidant species) with osmolyte behavior (retention of water by muscle). This review encompasses all these aspects by providing an illustrated metabolic account for brain and body creatine in health and disease, an algorithm to diagnose metabolic and gene bases of primary and secondary creatine deficiencies, and a metabolic exploration by (1)H-MRS assessment of cerebral creatine levels and response to therapeutic measures. PMID- 26542288 TI - Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via the PKC/ERK/c-Fos pathway in RAW264.7 macrophages. AB - BACKGROUND: Atherosclerosis is a major cause of coronary artery disease, which is characterized by cellular lipid accumulation. Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. Studies have shown that macrophage-derived LPL exhibits proatherogenic properties, and plays a major role in lipid accumulation in macrophages. Evidence suggests that oxidative stress can effectively enhance macrophage LPL production. Betulinic acid (BA) is a pentacyclic lupane triterpene with a potent antioxidant activity. In this study, we investigated whether BA affects the expression of macrophage LPL and how it regulates cellular lipid accumulation. METHODS AND RESULTS: We revealed that BA downregulated H2O2 simulated macrophage LPL protein, mRNA levels and its activity in both concentration- and time-dependent manners. Furthermore, BA decreased LPL-involved total cholesterol and triglyceride levels in macrophages. In addition, cellular lipid staining by Oil Red O showed that BA decreased cellular lipid droplet deposition. Next, we confirmed that pretreatment with BA decreased H2O2-induced production of intracellular reactive oxygen species in a concentration-dependent manner. Further studies demonstrated that BA inhibited H2O2-induced membrane translocation of PKC, phosphorylation of ERK1/2 and c-Fos. Finally, the induction of LPL production and activity by H2O2 was abolished by BA, inhibition of PKC or ERK or depletion c-Fos, respectively. CONCLUSIONS: BA, through its role of antioxidant activity, attenuated macrophage-derived LPL expression and activity induced by oxidative stress, and effectively reduced cellular lipid accumulation, likely through inhibition of the pathways involving PKC, ERK and c-Fos. These effects of BA may contribute to its mitigation of atherosclerosis and help develop BA as a therapeutic compound in treatment of atherosclerosis. PMID- 26542289 TI - Structural evolution of the 4/1 genes and proteins in non-vascular and lower vascular plants. AB - The 4/1 protein of unknown function is encoded by a single-copy gene in most higher plants. The 4/1 protein of Nicotiana tabacum (Nt-4/1 protein) has been shown to be alpha-helical and predominantly expressed in conductive tissues. Here, we report the analysis of 4/1 genes and the encoded proteins of lower land plants. Sequences of a number of 4/1 genes from liverworts, lycophytes, ferns and gymnosperms were determined and analyzed together with sequences available in databases. Most of the vascular plants were found to encode Magnoliophyta-like 4/1 proteins exhibiting previously described gene structure and protein properties. Identification of the 4/1-like proteins in hornworts, liverworts and charophyte algae (sister lineage to all land plants) but not in mosses suggests that 4/1 proteins are likely important for plant development but not required for a primary metabolic function of plant cell. PMID- 26542290 TI - Monaural or binaural sound deprivation in postlingual hearing loss: Cochlear implant in the worse ear. AB - OBJECTIVES/HYPOTHESIS: To determine whether speech recognition scores (SRS) differ between adults with long-term auditory deprivation in the implanted ear and adults who received cochlear implant (CI) in the nonsound-deprived ear, either for hearing aid-assisted or due to rapidly deteriorating hearing loss. STUDY DESIGN: Retrospective study. METHODS: Speech recognition scores at evaluations (3 and 14 months postimplantation) conducted with CI alone at 60-dB sound pressure level intensity were compared in 15 patients (4 with bilateral severe hearing loss; 11 with asymmetric hearing loss, 7 of which had contralateral hearing aid), all with long-term auditory deprivation (mean duration 16.9 years) (group A), and in 15 other patients with postlingual hearing loss (10 symmetric, 5 asymmetric with bimodal stimulation) (controls, group B). RESULTS: Comparison of mean percentage of correctly recognized words on speech audiometry at 3 and 14 months showed improvement within each group (P < 0.05). Between-group comparison showed no significant difference at 3 (P = 0.17) or 14 months (P = 0.46). Comparison of SRSs in group A (bimodal stimulation [n = 7] and binaural sound deprivation [n = 4]) versus group B showed no significant differences at 3 (bimodal stimulation P = 0.16; binaural sound deprivation P = 0.19) or 14 months (bimodal stimulation P = 0.14; binaural sound deprivation P = 0.82). CONCLUSIONS: Speech recognition scores in monaural and binaural sound deprived ears did not significantly differ from ears with unilateral cochlear implantation in nonsound-deprived ears when tested with CI alone. Improvement in the implanted worse ear indicates that it could be a potential candidate ear for cochlear implantation even when sound deprived. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1905-1910, 2016. PMID- 26542291 TI - miRNA-221 is elevated in cystic fibrosis airway epithelial cells and regulates expression of ATF6. AB - BACKGROUND: MicroRNA (miRNA) and messenger RNA (mRNA) expression differs in cystic fibrosis (CF) versus non-CF bronchial epithelium. Here, the role of miRNA in basal regulation of the transcription factor ATF6 was investigated in bronchial epithelial cells in vitro and in vivo. METHODS: Using in silico analysis, miRNAs predicted to target the 3'untranslated region (3'UTR) of the human ATF6 mRNA were identified. RESULTS: Three of these miRNAs, miR-145, miR-221 and miR-494, were upregulated in F508del-CFTR homozygous CFBE41o- versus non-CF 16HBE14o- bronchial epithelial cells and also in F508del-CFTR homozygous or heterozygous CF (n = 8) versus non-CF (n = 9) bronchial brushings. ATF6 was experimentally validated as a molecular target of these miRNAs through the use of a luciferase reporter vector containing the full-length 3'UTR of ATF6. Expression of ATF6 was observed to be decreased in CF both in vivo and in vitro. miR-221 was also predicted to regulate murine ATF6, and its expression was significantly increased in native airway tissues of 6-week-old betaENaC-overexpressing transgenic mice with CF-like lung disease versus wild-type littermates. CONCLUSIONS: These results implicate miR-145, miR-221 and miR-494 in the regulation of ATF6 in CF bronchial epithelium, with miR-221 demonstrating structural and functional conservation between humans and mice. The altered miRNA expression evident in CF bronchial epithelial cells can affect expression of transcriptional regulators such as ATF6. PMID- 26542292 TI - Bronchopulmonary dysplasia - an overview about pathophysiologic concepts. AB - Neonatal chronic lung disease in the preterm infant, i.e. bronchopulmonary dysplasia (BPD) is characterized by impaired pulmonary development with its effects persisting into adulthood. Triggered in the immature lung by infectious complications, oxygen toxicity and the impact of mechanical ventilation, a sustained inflammatory response, extensive remodeling of the extracellular matrix, increased apoptosis as well as altered growth factor signaling characterize the disease. The current review focuses on selected pathophysiologic processes and their interplay in disease development. Furthermore, the potential of both, acute and long-term changes to the pulmonary scaffold and the cellular interface in concert with dysregulated growth factor signaling to affect aging and repair processes in the adult lung is discussed. PMID- 26542293 TI - The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases. AB - Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases. PMID- 26542294 TI - Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia. AB - BACKGROUND: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia. METHODS: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers. RESULTS: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl d-aspartate (NMDA) receptor. CONCLUSIONS: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway. PMID- 26542295 TI - Characterization of maturation of neuronal voltage-gated sodium channels SCN1A and SCN8A in rat myocardium. AB - BACKGROUND: Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium. METHODS: The expression of neuronal sodium channels (SCN1A, SCN8A) and the cardiac isoform SCN5A in the developing rat myocardium was studied by rtPCR, Western blot, and immunohistochemistry at different stages of antenatal and postnatal development. RESULTS: Significant changes of sodium channel expression during development were detected. Whereas SCN5A RNA increased to maximum levels on day 21 after birth, the highest SCN1A RNA levels were detected on day 1 to 7 after birth. SCN8A RNA was maximally expressed during embryonic development. At the protein level, the amount of SCN5A protein increased along with the RNA level. SCN1A protein level decreased after birth in contrast to RNA expression. Western blot could not detect SCN8A protein in the myocardium at any stage of development. Immunohistochemistry however proved the presence of SCN8A protein in the developing rat myocardium. CONCLUSIONS: Heart- and brain-type sodium channels are differentially expressed during ontogenesis. The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life. Altered regulation of sodium channels might result in severe cardiac rhythm disturbances. PMID- 26542297 TI - Submicroscopic copy-number variations associated with 46,XY disorders of sex development. AB - BACKGROUND: Mutations in known causative genes and cytogenetically detectable chromosomal rearrangements account for a fraction of cases with 46,XY disorders of sex development (DSD). Recent advances in molecular cytogenetic technologies, including array-based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA), have enabled the identification of copy-number variations (CNVs) in individuals with apparently normal karyotypes. FINDINGS: This review paper summarizes the results of 15 recent studies, in which aCGH or MLPA were used to identify CNVs. Several submicroscopic CNVs have been detected in patients with 46,XY DSD. These CNVs included deletions involving known causative genes such as DMRT1 or NR5A1, duplications involving NR0B1, deletions involving putative cis-regulatory elements of SOX9, and various deletions and duplications of unknown pathogenicity. CONCLUSIONS: The results of recent studies highlight the significance of submicroscopic CNVs as the genetic basis of 46,XY DSD. Molecular cytogenetic analyses should be included in the diagnostic workup of patients with 46,XY DSD of unknown origin. Further studies using aCGH will serve to clarify novel causes of this condition. PMID- 26542298 TI - Ciliopathies - from rare inherited cystic kidney diseases to basic cellular function. AB - BACKGROUND: Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment. While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research. FINDINGS: Cilia are nowadays considered to be crucial cellular structures controlling diverse intracellular signaling cascades. Dysfunction of cilia leads to a pleiotropic group of diseases ranging from cystic kidney disease via neurologic disorders to metabolic phenotypes and cardiac malformations. According to the underlying cellular pathophysiology, these diverse disorders have been subsumed under the term "ciliopathies". CONCLUSIONS: The work on rare human ciliopathies has strongly deepened our genetic and cell biological understanding of multiple diseases and cellular events thus ultimately leading to clinical trials of novel therapeutic approaches. This review focuses on some of the important developments in ciliopathy research. PMID- 26542296 TI - Metabolic origins of childhood asthma. AB - Childhood obesity and incidence of asthma are increasing globally. The parallel increase of the two suggests that obesity and asthma may be related and that abnormalities in the lipid and/or glucose metabolism may contribute to the pathogenesis of asthma. The clinical presentation of obese asthma is distinct from other asthma phenotypes and depending on age of onset of symptoms. Asthma in obese people tends to be more severe, not typically associated with allergy, and less responsive to standard anti-inflammatory therapy, including corticosteroids. Obesity and obesity-related comorbidities may lead to asthma via a number of mechanisms including changes in lung mechanics, the nitric oxide metabolism, and by causing inflammation. Furthermore, evidence suggests that nutrition during pregnancy contributes to intrauterine immune and metabolic programming in the offspring, which may have major influences on predisposition to cardiovascular, metabolic, and allergic diseases, including asthma, later in life. This review will highlight some suggested mechanistic links between obesity and diabetes with asthma. PMID- 26542299 TI - Lessons learned from metabolomics in cystic fibrosis. AB - Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or pathomechanisms in cystic fibrosis (CF) have included blood, respiratory secretions, and exhaled breath to date. Metabolomics has shown distinction of CF vs. non-CF for matrices of blood, exhaled breath, and respiratory epithelial cultures, each showing different pathways. Severity of lung disease has been addressed by studies in bronchoalveolar lavage and exhaled breath condensate showing separation by metabolites that the authors of each study related to inflammation; e.g., ethanol, acetone, purines. Lipidomics has been applied to blood and sputum samples showing associations with lung function and Pseudomonas aeruginosa infection status. Finally, studies of bacteria grown in vitro showed differences of bacterial metabolites to be associated with clinical parameters. Metabolomics, in the sense of global metabolomic profiling, is a powerful technique that has allowed discovery of pathways that had not previously been implicated in CF. These may include purines, mitochondrial pathways, and different aspects of glucose metabolism besides the known differences in lipid metabolism in CF. However, targeted studies to validate such potential metabolites and pathways of interest are necessary. Studies evaluating metabolites of bacterial origin are in their early stages. Thus further well designed studies could be envisioned. PMID- 26542300 TI - Stent implantation into the tracheo-bronchial system in rabbits: histopathologic sequelae in bare metal vs. drug-eluting stents. AB - BACKGROUND: Stent implantation into the tracheo-bronchial system may be life saving in selected pediatric patients with otherwise intractable stenosis of the upper airways. Following implantation, significant tissue proliferation may occur, requiring re-interventions. We sought to evaluate the effect of immunosuppressive coating of the stents on the extent of tissue proliferation in an animal model. METHODS: Bare metal and sirolimus-coated stents (Bx Sonic and Cypher Select, Johnson & Johnson, Cordis) were implanted into non-stenotic lower airways of New Zealand white rabbits (weight 3.1 to 4.8 kg). Three stents with sirolimus coating and six bare metal stents could be analyzed by means of histology and immunohistochemistry 12 months after implantation. RESULTS: On a macroscopic evaluation, all stents were partially covered with a considerable amount of whitish tissue. Histologically, these proliferations contained fiber rich connective tissue and some fibromuscular cells without significant differences between both stent types. The superficial tissue layer was formed by typical respiratory epithelium and polygonal cells. Abundant lymphocyte infiltrations and moderate granulocyte infiltrations were found in both groups correspondingly, whereas foreign-body reaction was more pronounced around sirolimus-eluting stents. CONCLUSIONS: After stent implantation in the tracheo bronchial system of rabbits, we found tissue reactions comparable to those seen after stent implantation into the vascular system. There was no difference between coated and uncoated stents with regard to quality and quantity of tissue proliferation. We found, however, a significantly different inflammatory reaction with a more pronounced foreign-body reaction in sirolimus-coated stents. In our small series, drug-eluting stents did not exhibit any benefit over bare metal stents in an experimental setting. PMID- 26542301 TI - Resolving Uncertainty About the Intolerance of Uncertainty Scale-12: Application of Modern Psychometric Strategies. AB - In this study, we evaluated the factor structure, reliability estimates, item parameters, and differential correlates of the short form of the Intolerance of Uncertainty Scale (Carleton, Norton, & Asmundson, 2007 ) in samples of undergraduate women (n = 387) and men (n = 276) ranging in age from 18 to 49 years (M = 20.20, SD = 3.91). This instrument was designed to measure 2 facets of intolerance of uncertainty-prospective anxiety and inhibitory anxiety-although total scores on the measure are often used. A major objective of this study was to determine the degree to which derivation of total versus subscale scores is empirically permissible. Comparison of a bifactor model to a unidimensional model and a 2-factor correlated traits model indicated that the bifactor model exhibited superior fit to the sample data. This model provided evidence of a strong general intolerance of uncertainty factor that was more reliable and accounted for significantly more common variance than either subscale factor. Examination of the item response theory slope parameters revealed negligible bias in the measure's items across genders. Finally, a series of simultaneous regression analyses was conducted to examine differential correlates of the measure's total scale scores for men and women. PMID- 26542302 TI - Promotoras Can Facilitate Use of Recreational Community Resources: The Mi Corazon Mi Comunidad Cohort Study. AB - INTRODUCTION: Limited research has documented interventions aimed at promoting use of existing recreational community resources among underserved populations. This study (HEART [Health Education Awareness Research Team] Phase 2) reports findings of an intervention (Mi Corazon Mi Comunidad) where community health workers facilitated use of diet and exercise programming at local recreational facilities among Mexican American border residents. The aim was to evaluate overall attendance rates and to assess which factors predicted higher attendance. METHOD: The design was a cohort study. From 2009 to 2013, a total of 753 participants were recruited across 5 consecutive cohorts. The intervention consisted of organized physical activity and nutrition programming at parks and recreational facilities and a free YWCA membership. Attendance at all activities was objectively recorded. Regression analyses were used to evaluate whether demographic factors, health status, and health beliefs were associated with attendance. Results Participants included mostly females at high risk for cardiovascular disease (72.4% were overweight/obese and 64% were [pre ]hypertensive). A total of 83.6% of participants attended at least one session. On average, total attendance was 21.6 sessions (range: 19.1-25.2 sessions between the different cohorts), including 16.4 physical activity and 5.2 nutrition sessions. Females (p = .003) and older participants (p < .001) attended more sessions. Participants low in acculturation (vs. high) attended on average seven more sessions (p = .003). Greater self-efficacy (p < .001), perceived benefits (p = .038), and healthy intentions (p = .024) were associated with higher attendance. Conclusions The intervention was successful in promoting use of recreational facilities among border residents at high risk for cardiovascular disease. Findings were similar across five different cohorts. PMID- 26542303 TI - A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells. AB - Small molecule compounds promoting the neuronal differentiation of stem/progenitor cells are of pivotal importance to regenerative medicine. We carried out a high-content screen to systematically characterize known bioactive compounds, on their effects on the neuronal differentiation and the midbrain dopamine (mDA) neuron specification of neural progenitor cells (NPCs) derived from the ventral mesencephalon of human fetal brain. Among the promoting compounds three major pharmacological classes were identified including the statins, TGF-betaRI inhibitors, and GSK-3 inhibitors. The function of each class was also shown to be distinct, either to promote both the neuronal differentiation and mDA neuron specification, or selectively the latter, or promote the former but suppress the latter. We then carried out initial investigation on the possible mechanisms underlying, and demonstrated their applications on NPCs derived from human pluripotent stem cells (PSCs). Our study revealed the potential of several small molecule compounds for use in the directed differentiation of human NPCs. The screening result also provided insight into the signaling network regulating the differentiation of human NPCs. PMID- 26542304 TI - Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis. AB - OBJECTIVES: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC beta-lactamase. METHODS: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad spectrum beta-lactam/beta-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. REGISTRATION: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). RESULTS: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. CONCLUSIONS: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems. PMID- 26542305 TI - Infection by and dissemination of NDM-5-producing Escherichia coli in China. PMID- 26542306 TI - Inhibition of herpes simplex virus type 1 by the CDK6 inhibitor PD-0332991 (palbociclib) through the control of SAMHD1. AB - OBJECTIVES: Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) has been shown to restrict retroviruses and DNA viruses by decreasing the pool of intracellular deoxynucleotides. In turn, SAMHD1 is controlled by cyclin-dependent kinases (CDK) that regulate the cell cycle and cell proliferation. Here, we explore the effect of CDK6 inhibitors on the replication of herpes simplex virus type 1 (HSV-1) in primary monocyte-derived macrophages (MDM). METHODS: MDM were treated with palbociclib, a selective CDK4/6 inhibitor, and then infected with a GFP-expressing HSV-1. Intracellular deoxynucleotide triphosphate (dNTP) content was determined using a polymerase-based method. RESULTS: CDK6 inhibitor palbociclib blocked SAMHD1 phosphorylation, intracellular dNTP levels and HSV-1 replication in MDM at subtoxic concentrations. Treatment of MDM with palbociclib reduced CDK2 activation, measured as the phosphorylation of the T-loop at Thr160. The antiviral activity of palbociclib was lost when SAMHD1 was degraded by viral protein X. Similarly, palbociclib did not block HSV-1 replication in SAMHD1-negative Vero cells at subtoxic concentrations, providing further evidence for a role of SAMHD1 in mediating the antiviral effect. CONCLUSIONS: SAMHD1-mediated HSV-1 restriction is controlled by CDK and points to a preferential role for CDK6 and CDK2 as mediators of SAMHD1 activation. Similarly, the restricting activity of SAMHD1 against DNA viruses suggests that control of dNTP availability is the major determinant of its antiviral activity. This is the first study describing the anti-HSV-1 activity of palbociclib. PMID- 26542308 TI - Gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism for increased ERG expression in acute myeloid leukemia. AB - In acute myeloid leukemia (AML), acquired genomic gains and losses are common and lead to altered expression of genes located within or nearby the affected regions. Increased expression of the ETS-related transcription factor gene ERG has been described in myeloid malignancies with chromosomal rearrangements involving chromosome band 21q22, but also in cytogenetically normal AML, where it is associated with adverse prognosis. In this study, fluorescence in situ hybridization on interphase nuclei disclosed an amplification of the ERG gene (more than six copies) in 33 AML patients with structural rearrangements of 21q22. Array comparative genomic hybridization of these cases disclosed a minimal amplified region at the position 39.6-40.0 Mbp from pter that harbors ERG as the only gene. Analysis by quantitative real-time reverse transcription polymerase chain reaction revealed significantly higher ERG mRNA expression in these patients and in a group of 95 AML patients with complete or partial gain of chromosome 21 (three to six copies) compared with 351 AML patients without gain of chromosome 21. Quantification of ERG DNA copy numbers revealed a strong correlation with ERG mRNA expression. Furthermore, in patients with gain of chromosome 21, higher ERG expression was found to be associated with RUNX1 mutations. Our results suggest that acquired gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism contributing to increased ERG expression in AML. PMID- 26542309 TI - Protective effect of Ganshuang Granules () on liver cirrhosis by suppressing regulatory T cells in a mouse model. AB - OBJECTIVE: To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (, GSG) and to provide clinical therapeutic evidence of its effects. METHODS: A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl4 (40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling, GSG was intragastric administrated to the mice for 2 weeks, and the mice were divided into low-, medium- and high-dose groups at doses of 1, 2 and 4 g/(kg.day), respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin, smooth muscle actin (SMA) and Foxp3 in liver were detected by immunoflfluorescence. The regulatory T cell (Treg) frequency was determined through flflow cytometry analysis. Collagen-I, SMA, IL-6, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and transforming growth factor beta1 (TGF-beta1) expression levels were measured using quantitative polymerase chain reaction (qPCR). RESULTS: Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT, AST, HA levels were significantly ameliorated by GSG treatment (ALT: F=8.104, P=0.000; AST: F=7.078, P=0.002; and HA: F=7.621, P=0.001). The expression levels of collagen-I and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-I: F=3.938, P=0.011; SMA: F=4.115, P=0.009). Tregs, which were elevated in the fibrotic livers, were suppressed by GSG treatment (F=8.268, P=0.001). The expressions of IL-6, TNF-alpha and IL-1beta increased, and TGF-beta levels decreased in the cirrhotic livers after GSG treatment (IL-6: F=5.457, P=0.004; TNF-alpha: F=6.023, P=0.002; IL-1beta: F=6.658, P=0.001; and TGF-beta1: F=11.239, P=0.000). CONCLUSIONS: GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation, which may be mediated by hepatic stellate cells. PMID- 26542307 TI - Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity. AB - Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26542310 TI - Scaling human pluripotent stem cell expansion and differentiation: are cell factories becoming a reality? PMID- 26542311 TI - Management Issues in Intensive Care Units for Infants and Children with Heart Disease. AB - Admission of infants and children with cardiac disease to the neonatal (NICU) and pediatric ICU (PICU) is ever increasing in India (30-50 % of all admissions). The commonest indication for admission to the NICU or PICU is acute deterioration of cardiac disease. This includes: acute heart failure, hypercyanotic spells, arrhythmias, pericardial tamponade and sick cardiac neonates who need urgent intervention. Other increasingly frequent indications for ICU admission include heart failure with concomitant chest infection and impending respiratory failure and, severe cyanotic heart disease with various stroke syndromes. It is thus essential that a pediatrician be comfortable with the ICU management of such children and that low cost ICU modalities be utilized in order to reach out to as many children as feasible. It is heartening that there is renewed interest in inexpensive therapies like noninvasive ventilation and therapeutic hypothermia. PMID- 26542312 TI - Experimental evolution: Assortative mating and sexual selection, independent of local adaptation, lead to reproductive isolation in the nematode Caenorhabditis remanei. AB - Using experimental evolution, we investigated the contributions of ecological divergence, sexual selection, and genetic drift to the evolution of reproductive isolation in Caenorhabditis remanei. The nematodes were reared on two different environments for 100 generations. They were assayed for fitness on both environments after 30, 64, and 100 generations, and hybrid fitness were analyzed after 64 and 100 generations. Mating propensity within and between populations was also analyzed. The design allowed us to determine whether local adaptation was synchronous with pre- and postzygotic reproductive isolation. Prezygotic isolation evolved quickly but was unconnected with adaptation to the divergent environments. Instead, prezygotic isolation was driven by mate preferences favoring individuals from the same replicate population. A bottleneck treatment, meant to enhance the opportunity for genetic drift, had no effect on prezygotic isolation. Postzygotic isolation occurred in crosses where at least one population had a large fitness advantage in its "home" environment. Taken together, our results suggest that prezygotic isolation did not depend on drift or adaptation to divergent environments, but instead resulted from differences in sexual interactions within individual replicates. Furthermore, our results suggest that postzygotic isolation can occur between populations even when only one population has greater fitness in its home environment. PMID- 26542313 TI - Obesity and endometrial cancer: unanswered epidemiological questions. PMID- 26542314 TI - Dental trauma in showjumping - A trinational study between Switzerland, France and Germany. AB - AIM: Showjumping is one of the sporting activities with a high injury risk. Unpredictable behaviour of the horse, considerable speed and the height of the rider in the saddle make this sport to one of the most dangerous, with the highest risk of injury and the highest mortality rate per competitor. The aim of this study was to determine the frequency of dental trauma, the wearing of protective gear such as helmet, back protector and mouthguard as well as the knowledge of primary care after dental trauma. MATERIAL AND METHODS: Within the framework of this study, 608 female and male showjumpers from Switzerland, France and Germany were questioned in a personal interview consisting of 14 questions about general injuries, dental injuries and the usage of protective gear. The competitors were subdivided into different categories according to amateur or professional level, gender and age. RESULTS: Of the 608 competitors, 189 (31.1%) had witnessed an accident involving tooth injury and 91 (15.0%) had suffered one themselves. The prevalence of dental trauma rose with increasing age and more riding experience. A total of 436 (71.1%) of the competitors were familiar with mouthguards, of which only three owned one. The main reasons for not wearing a mouthguard were both doubtful necessity (22.5%) and a generally low acceptance among the riders (26.3%). Less than half of the competitors (44.4%) knew that an avulsed tooth can be replanted and only 4.1% had knowledge about the existence of a tooth rescue box. CONCLUSION: The results of this study show that in equestrian sports still little is known about dental trauma and protective measures. PMID- 26542315 TI - Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion. AB - Stem cells from human exfoliated deciduous teeth (SHEDs) can regenerate various tissues. We investigated the impact of SHED-conditioned medium (SHED-CM) on myocardial injury in a mouse model of ischemia-reperfusion (I/R). Wild-type (WT) mice were subjected to myocardial ischemia followed by reperfusion. SHED-CM was intravenously injected at 5 min after reperfusion. Administration of SHED-CM reduced myocardial infarct size as well as decreased apoptosis and inflammatory cytokine levels, such as TNF-alpha, IL-6, and IL-beta, in the myocardium following I/R. In cultured cardiac myocytes, SHED-CM significantly suppressed apoptosis under hypoxia/serum-deprivation and reduced LPS-induced expression of pro-inflammatory genes. Furthermore, anti-apoptotic action of SHED-CM was stronger than bone marrow-derived stem cell (BMSC)-CM or adipose-derived stem cell (ADSC)-CM in cardiac myocytes. SHED-CM contains a higher concentration of hepatocyte growth factor (HGF) than BMSC-CM and ADSC-CM, and neutralization of HGF attenuated the inhibitory actions of SHED-CM on apoptosis in cardiac myocytes. Finally, WT mice were intravenously treated with an HGF-depleted SHED CM, followed by myocardial I/R. HGF depletion significantly attenuated the inhibitory actions of SHED-CM on myocardial infarct size and apoptosis after I/R. SHED-CM protects the heart from acute ischemic injury because it suppresses inflammation and apoptosis. SHED-CM could be a useful treatment option for acute myocardial infarction. PMID- 26542316 TI - Metals in Urine and Diabetes in U.S. Adults. AB - Our objective was to evaluate the relationship of urine metals including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, and uranium with diabetes prevalence. Data were from a cross-sectional study of 9,447 participants of the 1999-2010 National Health and Nutrition Examination Survey, a representative sample of the U.S. civilian noninstitutionalized population. Metals were measured in a spot urine sample, and diabetes status was determined based on a previous diagnosis or an A1C >=6.5% (48 mmol/mol). After multivariable adjustment, the odds ratios of diabetes associated with the highest quartile of metal, compared with the lowest quartile, were 0.86 (95% CI 0.66-1.12) for barium (Ptrend = 0.13), 0.74 (0.51-1.09) for cadmium (Ptrend = 0.35), 1.21 (0.85-1.72) for cobalt (Ptrend = 0.59), 1.31 (0.90-1.91) for cesium (Ptrend = 0.29), 1.76 (1.24-2.50) for molybdenum (Ptrend = 0.01), 0.79 (0.56-1.13) for lead (Ptrend = 0.10), 1.72 (1.27-2.33) for antimony (Ptrend < 0.01), 0.76 (0.51-1.13) for thallium (Ptrend = 0.13), 2.18 (1.51-3.15) for tungsten (Ptrend < 0.01), and 1.46 (1.09-1.96) for uranium (Ptrend = 0.02). Higher quartiles of barium, molybdenum, and antimony were associated with greater HOMA of insulin resistance after adjustment. Molybdenum, antimony, tungsten, and uranium were positively associated with diabetes, even at the relatively low levels seen in the U.S. POPULATION: Prospective studies should further evaluate metals as risk factors for diabetes. PMID- 26542318 TI - An Improved Sparse Representation over Learned Dictionary Method for Seizure Detection. AB - Automatic seizure detection has played an important role in the monitoring, diagnosis and treatment of epilepsy. In this paper, a patient specific method is proposed for seizure detection in the long-term intracranial electroencephalogram (EEG) recordings. This seizure detection method is based on sparse representation with online dictionary learning and elastic net constraint. The online learned dictionary could sparsely represent the testing samples more accurately, and the elastic net constraint which combines the 11-norm and 12-norm not only makes the coefficients sparse but also avoids over-fitting problem. First, the EEG signals are preprocessed using wavelet filtering and differential filtering, and the kernel function is applied to make the samples closer to linearly separable. Then the dictionaries of seizure and nonseizure are respectively learned from original ictal and interictal training samples with online dictionary optimization algorithm to compose the training dictionary. After that, the test samples are sparsely coded over the learned dictionary and the residuals associated with ictal and interictal sub-dictionary are calculated, respectively. Eventually, the test samples are classified as two distinct categories, seizure or nonseizure, by comparing the reconstructed residuals. The average segment-based sensitivity of 95.45%, specificity of 99.08%, and event-based sensitivity of 94.44% with false detection rate of 0.23/h and average latency of -5.14 s have been achieved with our proposed method. PMID- 26542317 TI - Loss-of-Function Mutations in the Cell-Cycle Control Gene CDKN2A Impact on Glucose Homeostasis in Humans. AB - At the CDKN2A/B locus, three independent signals for type 2 diabetes risk are located in a noncoding region near CDKN2A. The disease-associated alleles have been implicated in reduced beta-cell function, but the underlying mechanism remains elusive. In mice, beta-cell-specific loss of Cdkn2a causes hyperplasia, while overexpression leads to diabetes, highlighting CDKN2A as a candidate effector transcript. Rare CDKN2A loss-of-function mutations are a cause of familial melanoma and offer the opportunity to determine the impact of CDKN2A haploinsufficiency on glucose homeostasis in humans. To test the hypothesis that such individuals have improved beta-cell function, we performed oral and intravenous glucose tolerance tests on mutation carriers and matched control subjects. Compared with control subjects, carriers displayed increased insulin secretion, impaired insulin sensitivity, and reduced hepatic insulin clearance. These results are consistent with a model whereby CDKN2A loss affects a range of different tissues, including pancreatic beta-cells and liver. To test for direct effects of CDKN2A-loss on beta-cell function, we performed knockdown in a human beta-cell line, EndoC-bH1. This revealed increased insulin secretion independent of proliferation. Overall, we demonstrated that CDKN2A is an important regulator of glucose homeostasis in humans, thus supporting its candidacy as an effector transcript for type 2 diabetes-associated alleles in the region. PMID- 26542319 TI - High-resolution pluronic-filled microchip CE-SSCP analysis system via channel width control. AB - Although the resolution of CE-SSCP has been significantly improved by using a poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO; Pluronic((r))) triblock copolymer as a separation medium, CE-SSCP on a microchip format is not widely applicable because their resolution is limited by short channel length. Therefore, a strategy to improve the resolution in channels of limited lengths is highly required for enabling microchip-based CE-SSCP. In this study, we developed a high-resolution CE-SSCP microchip system by controlling the width of the pluronic-filled channel. We tested four different channel widths of 180, 240, 300, and 400 MUm, and found that 300 MUm showed the highest resolution in the separation of two pathogen specific markers. Potential applications of our method in various genetic analyses were also shown by using SNP markers for spinal muscular atrophy. PMID- 26542320 TI - [Very late drug-eluting stent thrombosis by stent fracture]. AB - The superiority of drug-eluting stents in reducing the risk of in-stent restenosis compared to bare-metal stents is no longer challenged. Nevertheless, the drug-eluting stents may carry long-term risk of late and very late stent thrombosis. The promoting factors of this complication are usually divided into three chapters depending on the patient, the procedure and the stent. Indeed, the literature has reported several parameters related to the stent itself, such as its length, the malapposition, its diameter, but also more rarely the occurrence of stent fracture. We present the case of a patient admitted for myocardial infarction after a very late thrombosis of Cypher drug-eluting stent four years after its implantation and related to stent fracture. PMID- 26542321 TI - Silver(I)-Catalyzed Synthesis of beta-Oxopropylcarbamates from Propargylic Alcohols and CO2 Surrogate: A Gas-Free Process. AB - The utilization of carbon dioxide poses major challenges owing to its high thermodynamic stability and kinetic inertness. To circumvent these problems, a simple reaction system is reported comprising ammonium carbamates as carbon dioxide surrogates, propargylic alcohols, and a silver(I) catalyst, for the effective conversion of a wide range of alcohols and secondary amines into the corresponding beta-oxopropylcarbamates. A key feature of this strategy includes quantitative use of a carbon resource with high product yields under gas-free and mild reaction conditions. Notably, this catalytic protocol also works well for the carboxylative cyclization of propargylic amines and carbon dioxide surrogates to afford 2-oxazolidinones. PMID- 26542323 TI - Surgery is possible: now let's prove its superior efficacy! PMID- 26542322 TI - Scientific impact and beyond. PMID- 26542324 TI - How can we improve surgical outcomes? PMID- 26542325 TI - Frozen section during partial nephrectomy: an unreliable test that changes nothing? PMID- 26542326 TI - Are men who are biopsied without prior prostate magnetic resonance imaging getting substandard care? PMID- 26542327 TI - Cabazitaxel for the therapy of metastatic castration-resistant prostate cancer in the aftermath of the CHAARTED trial. PMID- 26542328 TI - Is the modified sliding technique the way forward in Peyronie's surgery? PMID- 26542329 TI - A simple and sensitive label-free fluorescence sensing of heparin based on Cdte quantum dots. AB - A rapid, simple and sensitive label-free fluorescence method was developed for the determination of trace amounts of an important drug, heparin. This new method was based on water-soluble glutathione-capped CdTe quantum dots (CdTe QDs) as the luminescent probe. CdTe QDs were prepared according to the published protocol and the sizes of these nanoparticles were verified through transmission electron microscopy (TEM), X-ray diffraction (XRD) and dynamic light scattering (DLS) with an average particle size of about 7 nm. The fluorescence intensity of glutathione capped CdTe QDs increased with increasing heparin concentration. These changes were followed as the analytical signal. Effective variables such as pH, QD concentration and incubation time were optimized. At the optimum conditions, with this optical method, heparin could be measured within the range 10.0-200.0 ng mL( 1) with a low limit of detection, 2.0 ng mL(-1) . The constructed fluorescence sensor was also applied successfully for the determination of heparin in human serum. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542331 TI - Geographical variations of risk factors associated with HCV infection in drug users in southwestern China. AB - Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30.0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62.0% of townships, and being married was negatively associated with HCV infection in 81.0% of townships. Senior high-school education or above was positively associated with HCV infection in 55.2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV. PMID- 26542330 TI - Effect of roflumilast on airway remodelling in a murine model of chronic asthma. AB - BACKGROUND: Airway remodelling is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Roflumilast is a selective phosphodiesterase-4 inhibitor that has an anti-inflammatory effect in chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to study the effect of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma. METHODS: BALB/c mice sensitized to ovalbumin (OVA) were chronically exposed to intranasal OVA administration twice a week for additional 3 months. Roflumilast was administered orally during the intranasal OVA challenge. A lung fibroblast cell line was used in the proliferation assay. RESULTS: Compared with control mice, mice chronically exposed to OVA developed eosinophilic airway inflammation, airway hyper-responsiveness (AHR), and exhibited features of airway remodelling. Administration of roflumilast significantly inhibited airway inflammation and AHR. Roflumilast also significantly decreased goblet cell hyperplasia and pulmonary fibrosis, which are parameters of airway remodelling. The levels of interleukin (IL)-4, IL-5, and IL-13 in the bronchoalveolar lavage (BAL) fluids were significantly lower in the roflumilast group. In vitro, roflumilast significantly inhibited stem cell factor (SCF)-induced cell proliferation of fibroblasts. The SCF concentration and mRNA expression in a murine model also significantly decreased with roflumilast treatment. CONCLUSIONS: These results suggest that the administration of roflumilast regulates airway inflammation, AHR, and airway remodelling in a model of chronic asthma. The beneficial effects from roflumilast may be related to the SCF/c-kit pathway. PMID- 26542333 TI - Correction: DMT1 iron uptake in the PNS: bridging the gap between injury and regeneration. PMID- 26542332 TI - Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin. AB - AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery Asberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD. PMID- 26542335 TI - Left ventricular outflow tract geometry and dynamics in aortic stenosis: implications for the echocardiographic assessment of aortic valve area. PMID- 26542334 TI - Post-radiation fibrosarcoma of the cerebrum associated with a prominent, lace like, perivascular, desmoplastic change. AB - An intra-axial tumor measuring about 4 cm was excised from the right temporal lobe of a 35-year-old woman, who had a past history of resection of craniopharyngioma and postoperative radiation 21 years earlier. The tumor involved both the cortex and white matter, but was not attached to the dura mater. It consisted of a dense, interlacing, fascicular proliferation of atypical fibroblastic cells and was associated with an extensive, lace-like, desmoplastic change mainly involving the perivascular region around the tumor and overlying the subarachnoid space. The histopathological features of the desmoplastic change resembled meningioangiomatosis, but no proliferation of meningothelial cells was noted. The patient has been free from recurrence for 12 months since the operation. The association of primary cerebral fibrosarcoma with an extensive, lace-like, perivascular, desmoplastic change has not been documented in the literature. The radiation administered 21 years previously may have played some pathogenetic role in the perivascular desmoplastic change, and a malignant transformation of fibroblasts within the perivascular collagenous tissue is considered the most likely origin of the fibrosarcoma. PMID- 26542336 TI - Cardio-oncology and echocardiography-partners in improving patient care. PMID- 26542338 TI - Words of gratitude for travel grants to the ASE Annual Scientific Sessions. PMID- 26542339 TI - Narcissism and Self-Insight: A Review and Meta-Analysis of Narcissists' Self Enhancement Tendencies. AB - The current article reviews the narcissism-self-enhancement literature using a multilevel meta-analytic technique. Specifically, we focus on self-insight self enhancement (i.e., whether narcissists perceive themselves more positively than they are perceived by others); thus, we only include studies that compare narcissists' self-reports to observer reports or objective measures. Results from 171 correlations reported in 36 empirical studies (N = 6,423) revealed that the narcissism-self-enhancement relationship corrected for unreliability in narcissism was .21 (95% confidence interval [CI] = [.17, .25]), and that narcissists tend to self-enhance their agentic characteristics more than their communal characteristics. The average corrected relationship between narcissism and self-enhancement for agentic characteristics was .29 (95% CI = [.25, .33]), whereas for communal characteristics it was .05 (95% CI = [-.01, .10]). In addition, we individually summarized narcissists' self-enhancement for 10 different constructs (i.e., the Big Five, task performance, intelligence, leadership, attractiveness, and likeability). PMID- 26542340 TI - A new validated HPLC method for the determination of sulforaphane: application to study pharmacokinetics of sulforaphane in rats. AB - A simple, accurate and reproducible high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of sulforaphane (SF) in rat plasma. The method involves a simple liquid-liquid extraction procedure to extract both SF and 7-hyrdoxycoumarin, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an isocratic mobile phase consisting of 10 mm KH2 PO4 (pH 4.5) and acetonitrile HPLC grade (40:60, v/v) run at a flow rate of 1 mL/min for 10 min. The UV detection wavelength was set at 202 nm. The method exhibited good linearity (R(2) > 0.999) over the assayed concentration range (0.05-2 MUg/mL) and demonstrated good intra- and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were <15%). This method was also successfully applied for studying the pharmacokinetics of SF in spontaneously hypertensive rats following single oral dietary doses of SF. The pharmacokinetics of SF show linear behavior at the dose range investigated in this study. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542341 TI - Corrigendum: A solid-solid phase transition in carbon dioxide at high pressures and intermediate temperatures. PMID- 26542342 TI - Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats. AB - Oxaliplatin, a widely used chemotherapeutic agent, induces peripheral neuropathy that manifests itself as two distinct phases: acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia. The latter is a serious dose limiting side effect that can often lead to withdrawal of treatment. We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan (GJG), a traditional Japanese herbal medicine, which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind randomized phase II study. In this study, neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks. The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later. Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks. Co-administration of GJG ameliorated both abnormal sensations as well as histological damage to the sciatic nerve. A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood. GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species, which is a possible mechanism of oxaliplatin-induced neurotoxicity. The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent. PMID- 26542344 TI - Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis. AB - Cognitive impairment has been well documented in HIV and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis indicated, however, that HIV mono-infected patients had a significantly higher global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of studies, heterogeneity of the samples, and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections. PMID- 26542343 TI - Effect of Regular Exercise on Inflammation Induced by Drug-resistant Staphylococcus aureus 3089 in ICR mice. AB - Obesity is often associated with irregular dietary habits and reduced physical activity. Regular exercise induces a metabolic response that includes increased expression of various cytokines, signaling proteins and hormones, and reduced adipocyte size. In this study, mice performed a swimming exercise for 10 min/day, 5 days/week for 3 weeks. We then investigated the effect of this exercise regimen on inflammation induced by infection with drug-resistant Staphylococcus aureus strain 3089 (DRSA). In humans, DRSA causes dermatitis and pneumonitis. Similarly, DRSA induced inflammatory pneumonitis in both no-exercise (No-EX) and swim trained (SW-EX) ICR mice. Regular exercise increased levels of the pro inflammatory cytokines TNF-alpha and IL-1beta and nitric oxide in both serum and whole lung tissue in SW-EX, as compared to No-EX control mice. Moreover, levels of the antimicrobial peptide cathelicidin were significantly increased in visceral adipose tissue and whole lung tissue in the SW-EX group, and this was accompanied by a reduction in the size of visceral adipocytes. In addition, levels of the inflammation marker peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) were not increased in the lung tissue of SW-EX mice. These findings suggest that in these model mice, regular exercise strengthens immune system responses, potentially preventing or mitigating infectious disease. PMID- 26542345 TI - The future of pharmaceutical manufacturing in the context of the scientific, social, technological and economic evolution. AB - Healthcare provision is one of the import elements of modern societies. Life sciences and technology has made substantial progress over the past century and is continuing to evolve exponentially in many different areas. The use of genotypic and phenotypic information in drug discovery and drug therapy, the increasing wealth around the world, growing patient involvement through information and communication technology and finally innovations in pharmaceutical manufacturing technology are transforming the provision of healthcare. The adoption of this new science and technology is going to happen due to the synergistic effects and visible benefits for the society and healthcare systems. The different aspects driving advanced pharmaceutical manufacturing are reviewed to identify future research direction to assure overall acceptance and adoption into healthcare practice. PMID- 26542346 TI - Quantitative surface topography assessment of directly compressed and roller compacted tablet cores using photometric stereo image analysis. AB - Surface topography, in the context of surface smoothness/roughness, was investigated by the use of an image analysis technique, MultiRayTM, related to photometric stereo, on different tablet batches manufactured either by direct compression or roller compaction. In the present study, oblique illumination of the tablet (darkfield) was considered and the area of cracks and pores in the surface was used as a measure of tablet surface topography; the higher a value, the rougher the surface. The investigations demonstrated a high precision of the proposed technique, which was able to rapidly (within milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately product optimization. PMID- 26542347 TI - Oral delivery of zoledronic acid by non-covalent conjugation with lysine deoxycholic acid: In vitro characterization and in vivo anti-osteoporotic efficacy in ovariectomized rats. AB - We assessed the possibility of changing the route of administration of zoledronic acid to an oral dosage form and its therapeutic efficacy in an estrogen-deficient osteoporosis rat model. To enhance oral bioavailability, we formed an ionic complex by electrostatic conjugation of zoledronic acid with lysine-linked deoxycholic acid (Lys-DOCA, an oral absorption enhancer). After forming the complex, the characteristic crystalline features of pure zoledronic acid disappeared completely in the powder X-ray diffractogram and differential scanning calorimetry thermogram, indicating that zoledronic acid existed in an amorphous form in the complex. In vitro permeabilities of zoledronic acid/Lys DOCA (1:1) (ZD1) and zoledronic acid/Lys-DOCA (1:2) (ZD2) complex across Caco-2 cell monolayers were 2.47- and 4.74-fold higher than that of zoledronic acid, respectively. Upon intra-jejunal administration to rats, the intestinal absorption of zoledronic acid was increased significantly and the resulting oral bioavailability of the ZD2 complex was determined to be 6.76+/-2.59% (0.548+/ 0.161% for zoledronic acid). Ovariectomized (OVX) rats showed 122% increased bone mineral density versus the OVX control at 12weeks after treatment with once weekly oral administration of ZD2 complex (16MUg/kg of zoledronic acid). Furthermore, rats treated with ZD2 complex orally showed significant improvement in the parameters of trabecular microarchitecture and bone strength: 149% higher bone volume fraction (BV/TV), 115% higher trabecular number (Tb.N), and 56% higher mean maximum load (Fmax) than in the OVX group. The trabecular microstructure and bone mechanical properties in the oral zoledronic acid group were not significantly changed compared with the OVX control. Thus, the oral ZD2 complex inhibited osteoporosis progression effectively by promoting osteogenesis and trabecular connectivity. The oral ZD2 complex would be expected to improve patient compliance by replacing the conventional injectable form and expand the indications, to include prophylaxis for osteoporosis and bone metastases. PMID- 26542348 TI - The multifaceted aspects of blood cell-derived microparticles: An intriguing aspect of my past subject of studies. PMID- 26542349 TI - Blood cell-derived microparticles and nanoparticles: Multifaceted topics for research. PMID- 26542350 TI - Platelet microparticles and cancer: An intimate cross-talk. AB - Blood cell-derived microparticles (MP), in general, and platelet MPs (PMPs), in particular, have emerged as important contributors, as well as markers, of the delicate balance between health and disease. They may, on one hand, have beneficial effects by supporting tissue repair and regeneration, as well as hemostasis, but may, on the other hand, be a pro-coagulant promoter leading to the thrombotic events seen in the context of cancer. PMPs can act as a direct tumor growth enhancer through the release of potent growth factors in the tumor micro-environment. Tumor engraftment can also be stimulated by the pro-angiogenic potentials of platelet growth factors released by PMPs. PMPs, by their pro inflammatory and immunomodulatory functions, can also exert an indirect role in the metastatic multistep process by helping malignant cells to escape from immunological surveillance. The possible detrimental effect of transfusions in cancer patients has been debated for several years and the role played by PMPs present in blood products is receiving specific attention, considering their propensity to trigger thrombosis and support tumors. The intimate PMP-tumors crosstalk may therefore result in pro-thrombotic states and a physiological state favorable to tumor growth, tethering and dissemination. Laboratory and experimental studies are needed to better unveil the contribution of PMPs as coagulation promoters, as well as potential markers and targets to treat cancer. PMID- 26542352 TI - Periodic Formation/Breakdown of Lamellar Aggregates with Anionic Cyanobiphenyl Surfactants. AB - This study reports unusual behavior of aqueous-phase lamellar aggregates with a new class of hybrid surfactant, CB-B2ES, having mesogenic units {6-[4-(4 cyanophenyl)phenyloxy]hexyl} and temperature-sensitive oxyethylated (butoxyethoxyethyl) tails. These tails are poorly miscible and likely to microsegregate if the surfactant molecules assemble. Lamellar aggregates appear at CB-B2ES concentrations higher than 5 wt % and were found to undergo repeat formation/breakdown periodically at 30 degrees C, with an average domain lifetime of ~10 s. To investigate effects of the temperature-sensitive oxyethylene units on the hydrophilic/lipophilic balance (HLB) of the CB-B2ES bilayers, a fluorescence probe 1-pyrene-carboxaldehide was solubilized in the mixtures to sense the micro-environmental polarities. Fluorimetric measurements suggested that the polarity of CB-B2ES bilayers is very similar to that of the non-ethoxylated CB-B2ES analogue at high temperatures (>=65 degrees C). However, for CB-B2ES, polarity increased with a decreasing temperature, in contrast with the small decrease in polarity observed for analogous non-ethoxylated bilayers. This is consistent with increased hydration of the oxyethylene units in CB-B2ES bilayers at low temperatures. The periodic formation/breakdown and cooling induced hydrophilicity of the CB-B2ES lamellar aggregates did not appear in the non-hybrid and/or non-ethoxylated surfactant systems. Therefore, the combination of two unsymmetrical tails, one containing oxyethylene units and the other containing cyanobiphenyl terminal tips, must play an important role promoting this unusual behavior. PMID- 26542353 TI - Molten salt medium synthesis of wormlike platinum silver nanotubes without any organic surfactant or solvent for methanol and formic acid oxidation. AB - In the current research, the PtxAgy (x/y = 86/14, 79/21, 52/48, 21/79, 11/89) nanoparticles (NPs) are synthesized in the KNO3-LiNO3 molten salts without using any organic surfactant or solvent. The SEM results suggest that when the content of Ag is higher than 48%, the wormlike PtxAgy nanotubes (NTs) can be synthesized. The diameter of the PtxAgyNTs shows a slow decrease with the increase of Ag content. The TEM and HRTEM results indicate that the growth of hollow PtxAgy NTs undergoes an oriented attachment process and a Kirkendall effect approach. The results of cyclic voltammetry (CV) measurement indicate that the Pt52Ag48 catalyst presents a remarkable enhancement for methanol electrooxidation, while the Pt86Ag14 catalyst prefers electrochemically oxidizing formic acid compared with that of the commercially available Pt black. PMID- 26542351 TI - Secondary structural analysis of the carboxyl-terminal domain from different connexin isoforms. AB - The connexin carboxyl-terminal (CxCT) domain plays a role in the trafficking, localization, and turnover of gap junction channels, as well as the level of gap junction intercellular communication via numerous post-translational modifications and protein-protein interactions. As a key player in the regulation of gap junctions, the CT presents itself as a target for manipulation intended to modify function. Specific to intrinsically disordered proteins, identifying residues whose secondary structure can be manipulated will be critical toward unlocking the therapeutic potential of the CxCT domain. To accomplish this goal, we used biophysical methods to characterize CxCT domains attached to their fourth transmembrane domain (TM4). Circular dichroism and nuclear magnetic resonance were complementary in demonstrating the connexin isoforms that form the greatest amount of alpha-helical structure in their CT domain (Cx45 > Cx43 > Cx32 > Cx50 > Cx37 ~ Cx40 ~ Cx26). Studies compared the influence of 2,2,2-trifluoroethanol, pH, phosphorylation, and mutations (Cx32, X-linked Charcot-Marie Tooth disease; Cx26, hearing loss) on the TM4-CxCT structure. While pH modestly influences the CT structure, a major structural change was associated with phosphomimetic substitutions. Since most connexin CT domains are phosphorylated throughout their life cycle, studies of phospho-TM4-CxCT isoforms will be critical toward understanding the role that structure plays in regulating gap junction function. PMID- 26542354 TI - Zahedan rhabdovirus, a novel virus detected in ticks from Iran. AB - BACKGROUND: Rhabdoviridae infect a wide range of vertebrates, invertebrates and plants. Their transmission can occur via various arthropod vectors. In recent years, a number of novel rhabdoviruses have been identified from various animal species, but so far only few tick-transmitted rhabdoviruses have been described. METHODS: We isolated a novel rhabdovirus, provisionally named Zahedan rhabdovirus (ZARV), from Hyalomma anatolicum anatolicum ticks collected in Iran. The full length genome was determined using 454 next-generation sequencing and the phylogenetic relationship to other rhabdoviruses was analyzed. Inoculation experiments in mammalian Vero cells and mice were conducted and a specific PCR assay was developed. RESULTS: The complete genome of ZARV has a size of 11,230 nucleotides (nt) with the typical genomic organization of Rhabdoviridae. Phylogenetic analysis confirms that ZARV is closely related to Moussa virus (MOUV) from West Africa and Long Island tick rhabdovirus (LITRV) from the U.S., all forming a new monophyletic clade, provisionally designated Zamolirhabdovirus, within the Dimarhabdovirus supergroup. The glycoprotein (G) contains 12 conserved cysteins which are specific for animal rhabdoviruses infecting fish and mammals. In addition, ZARV is able to infect mammalian Vero cells and is lethal for mice when inoculated intracerebrally or subcutaneously. The developed PCR assay can be used to specifically detect ZARV. CONCLUSION: The novel tick-transmitted rhabdovirus ZARV is closely related to MOUV and LITRV. All three viruses seem to form a new monophyletic clade. ZARV might be pathogenic for mammals, since it can infect Vero cells, is lethal for mice and its glycoprotein contains 12 conserved cysteins only found in animal rhabdoviruses. The mammalian host of ZARV remains to be identified. PMID- 26542355 TI - Dementia care in Ontario, Canada: evidence of more timely diagnosis among persons with dementia receiving care at home compared with residential facilities. AB - OBJECTIVE: Home care (HC) has been promoted as an efficient alternative to residential care (RC). However, little is known about the individuals who receive HC. This study compared the cognitive and functional statuses of persons with dementia receiving HC or RC at the time of diagnosis with dementia. It was hypothesized that persons with dementia receiving RC would have declined further, both cognitively and functionally. STUDY DESIGN: Population-based secondary data analysis. METHODS: Data from the Canadian Institute for Health Information's Continuing Care Reporting System and the Home Care Reporting System, 2009-2011, were used. Respective populations of 39,604 and 21,153 persons with dementia who received either RC or HC were included. Cognitive and functional statuses were measured using a cognitive performance scale (CPS) and an activities of daily living (ADL) scale, respectively. RESULTS: The mean CPS score was higher for the RC group (3.2 vs 2.5). The proportion of individuals diagnosed when impairment was moderate to very severe (CPS >= 4) was higher in the RC group (32.0% vs 13.3%). The mean ADL score was also higher for the RC group (3.5 vs 1.6). The proportion of individuals diagnosed when they required extensive assistance or were totally dependent (ADL >= 3) was markedly higher in the RC group (72.3% vs 27.3%). All findings were statistically significant (P < 0.0001). Multivariable analysis suggested that RC clients were nearly four times more likely than HC clients to be diagnosed at a later stage (odds ratio = 3.74, 95% confidence interval 3.54-3.95). CONCLUSIONS: Persons with dementia in RC facilities in Ontario are diagnosed when their cognitive and functional statuses have declined more than those of their HC counterparts. PMID- 26542356 TI - The language of the masses. PMID- 26542357 TI - Contribution of draft cattle to rural livelihoods in a district of southeastern Uganda endemic for bovine parasitic diseases: an economic evaluation. AB - BACKGROUND: A study was conducted in Tororo District in eastern Uganda to assess the socio-economic contribution of draft cattle to rural livelihoods. The aim of the study was to empirically quantify the economic value of draft cattle thus contributing to understanding the impact of endemic parasitic diseases of cattle on livestock productivity and subsequently household income, labor and food security. METHOD: A total of 205 draft cattle keeping households (n = 205) were randomly selected and structured household questionnaires were administered, focusing on work oxen use, productivity, inputs and outputs. The data obtained was analyzed using standard statistical methods and used to calculate the gross margin from the draft cattle enterprise. Secondary data were obtained from focus group discussions and key informant interviews and these were analyzed using Bayesian methods. RESULTS: The study showed that, apart from being labor saving, the use of animal traction is highly profitable with the gross margin per year from the use of draft cattle amounting to 245 United States dollars per work oxen owning household. The cash obtained from hiring out draft animals was equivalent to nearly a quarter of the average local household's monetary receipts. It also revealed that endemic bovine parasitic diseases such as trypanosomiasis and tick borne diseases reduced draft cattle output by 20.9 % and potential household income from the use of draft oxen by 32.2 %. CONCLUSION: The presence of endemic cattle diseases in rural Uganda is adversely affecting the productivity of draft cattle, which in turn affects household income, labor and ultimately food security. This study highlights the contribution of draft cattle to rural livelihoods, thus increasing the expected impact of cost-effective control strategies of endemic production limiting livestock diseases in Uganda. PMID- 26542358 TI - Nonlinear receding horizon guidance for spacecraft formation reconfiguration on libration point orbits using a symplectic numerical method. AB - This paper studies a nonlinear receding horizon control guidance strategy for spacecraft formation reconfiguration on libration orbits in the Sun-Earth system. For comparison, a linear quadratic soft terminal control strategy is also considered for the same reconfiguration missions. A novel symplectic iterative numerical algorithm is proposed to obtain the optimal solution for the nonlinear receding horizon control strategy at each update instant. With the aid of the quasilinearization method, a high-efficiency structure-preserving symplectic method is introduced in the iterations, and the optimal control problem is replaced successfully by a series of sparse symmetrical linear equations. Several typical spacecraft formation reconfiguration missions including resizing, rotating and slewing reconfigurations and their combinations are numerically simulated to show the effectiveness of the nonlinear receding horizon guidance strategy based on the proposed symplectic algorithm. Through these simulations, the nonlinear receding horizon control strategy is shown to have obvious advantages in convergence and parameter sensitivity compared with a linear quadratic soft terminal control strategy. Monte Carlo stochastic simulations are used to test the robustness of the nonlinear receding horizon control guidance in dealing with measurement and execution errors. PMID- 26542359 TI - Rolling element bearing defect detection using the generalized synchrosqueezing transform guided by time-frequency ridge enhancement. AB - Healthy rolling element bearings are vital guarantees for safe operation of the rotating machinery. Time-frequency (TF) signal analysis is an effective tool to detect bearing defects under time-varying shaft speed condition. However, it is a challenging work dealing with defective characteristic frequency and rotation frequency simultaneously without a tachometer. For this reason, a technique using the generalized synchrosqueezing transform (GST) guided by enhanced TF ridge extraction is suggested to detect the existence of the bearing defects. The low frequency band and the resonance band are first chopped from the Fourier spectrum of the bearing vibration measurements. The TF information of the lower band component and the resonance band envelope are represented using short-time Fourier transform, where the TF ridge are extracted by harmonic summation search and ridge candidate fusion operations. The inverse of the extracted TF ridge is subsequently used to guide the GST mapping the chirped TF representation to the constant one. The rectified TF pictures are then synchrosqueezed as sharper spectra where the rotation frequency and the defective characteristic frequency can be identified, respectively. Both simulated and experimental signals were used to evaluate the present technique. The results validate the effectiveness of the suggested technique for the bearing defect detection. PMID- 26542360 TI - Significantly improved solvent tolerance of Escherichia coli by global transcription machinery engineering. AB - BACKGROUND: Escherichia coli has emerged as a promising platform microorganism to produce biofuels and fine chemicals of industrial interests. Certain obstacles however remain to be overcome, among which organic-solvent tolerance is a crucial one. RESULTS: We used global transcription machinery engineering (gTME) to improve the organic-solvent tolerance (OST) of E. coli JM109. A mutant library of sigma(70) encoded by rpoD was screened under cyclohexane pressure. E. coli JM109 strain harboring sigma(70) mutant C9 was identified with capability of tolerating 69 % cyclohexane. The rpoD mutant contains three amino-acid substitutes and a stop-codon mutation, resulting a truncated sequence containing regions sigma(1.1) and sigma(1.2). Total protein difference produced by E. coli JM109 strain harboring C9 was examined with 2D-PAGE, and 204 high-abundant proteins showed over twofold variation under different solvent stress. CONCLUSIONS: Our results show that several genes (gapA, sdhB, pepB and dppA) play critical roles in enhanced solvent tolerance of E. coli, mainly involving in maintaining higher intracellular energy level under solvent stress. Global transcription machinery engineering is therefore a feasible and efficient approach for engineering strain with enhanced OST-phenotype. PMID- 26542361 TI - Different expression of VEGF and EGFL7 in human hepatocellular carcinoma. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is one of several angiogenic factors expressed in cirrhosis and during progression to malignancy, that seem to play a major role in hepatocellular carcinoma development. Lately, another angiogenic factor, epidermal growth factor-like domain multiple 7 (EGFL7), has attracted interest due to its possible relationship with hepatocellular carcinoma metastasis. AIMS: To evaluate expression of VEGF and EGFL7 in human hepatocellular carcinoma, compared to corresponding cirrhotic surrounding tissue. METHODS: Tumoural and cirrhotic tissue was harvested from 12 consecutive patients undergoing surgical resection. VEGF and EGFL7 were assessed by immunofluorescence and quantitative reverse transcriptase-polymerase chain reaction, compared with normal controls. RESULTS: Both angiogenic factors were over-expressed in cirrhotic livers compared to normal controls. VEGF and EGFL7 expressions did not differ according to disease aetiology, nodule size or other clinical variables. While VEGF expression was constant, regardless of tumour differentiation stage and unchanged compared to surrounding cirrhotic tissue, EGFL7 expression increased in less differentiated hepatocellular carcinoma. CONCLUSIONS: The preferential expression of EGFL7 in less differentiated hepatocellular carcinoma compared to VEGF, suggests a possible important role of this angiogenic factor in a later oncogenic and infiltrative/metastatic phase. PMID- 26542362 TI - Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer. AB - The genetic and epigenetic alterations occurring during the course of multistage colorectal carcinogenesis have been extensively studied in the last few decades. One of the most notable findings is that the great majority of colorectal cancers (>80%) have mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Loss of functional APC protein results in activation of canonical Wnt/beta catanin signaling and initiates intestinal carcinogenesis. Mutational inactivation of APC is the first genetic event, but colorectal cancer cells retain their dependency on constitutive Wnt signal activation even after accumulation of other genetic events. Accordingly, pharmacological blocking of Wnt signaling has been considered an attractive therapeutic approach for colorectal cancer. Several therapeutics targeting various molecular components of the Wnt signaling pathway, including porcupine, frizzled receptors and co receptor, tankyrases, and cAMP response element binding protein (CREB)-binding protein (CBP), have been developed, and some of those are currently being evaluated in early-phase clinical trials. Traf2- and Nck-interacting protein kinase (TNIK) has been identified as a regulatory component of the T-cell factor 4 and beta-catenin transcriptional complex independently by two research groups. TNIK regulates Wnt signaling in the most downstream part of the pathway, and its inhibition is expected to block the signal even in colorectal cancer cells with APC gene mutation. Here we discuss some of the TNIK inhibitors under preclinical development. PMID- 26542364 TI - Radiographic measurements of the hooves of normal ponies. AB - Knowledge of the normal radiographic anatomy of the equine foot and the relationship between the distal phalanx and the hoof capsule is imperative for objective assessment of hoof health. Little information is available for the hooves of ponies. The aim of this study was to establish a database of reference values for normal ponies and to investigate the relationship between the height at the withers and radiographic measurements of the hooves. Radiographic examinations were performed on 81 ponies, ranging from 81.5 to 148.0 cm height at the withers, immediately after foot trimming. Eighteen parameters were measured in the lateromedial view (front and hind feet) and 13 parameters were measured in the dorsopalmar view (front feet). Most linear measurements had a strong positive correlation with the height at the withers. The influence of height on angular measurements was weak. A linear regression model was adopted to enable calculation of reference values for a defined height at the withers. Left feet were longer in 72% of front feet and 67% of hind feet. The medial part of the hoof was more upright generally, but the medial hoof wall was shorter only in the right front feet. The front feet tended to be more upright than the hind feet. Compared to height at the withers, the hooves of ponies were relatively larger than the hooves of adult Warmblood horses investigated in a comparable study. The present study provides a database for farriers and veterinarians for hoof conformation, on the basis of which hoof preparation and an accurate diagnosis of lameness can be made. PMID- 26542363 TI - Clonidine for sedation in the critically ill: a systematic review and meta analysis (protocol). AB - BACKGROUND: Management and choice of sedation is important during critical illness in order to reduce patient suffering and to facilitate the delivery of care. Unfortunately, medications traditionally used for sedation in the intensive care unit (ICU) such as benzodiazepines and propofol are associated with significant unwanted effects. Clonidine is an alpha-2 selective adrenergic agonist that may have a role in optimizing current sedation practices in the pediatric and adult critically ill populations by potentially minimizing exposure to other sedative agents. METHODS/DESIGN: We will search MEDLINE, EMBASE, CINAHL, ACPJC, the Cochrane trial registry, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and clinicaltrials.gov for eligible observational studies and randomized controlled trials investigating the use of clonidine as an adjunctive or stand-alone sedative agent in patients requiring invasive mechanical ventilation. Our primary outcome is the duration of mechanical ventilation. Secondary outcomes include the following, listed by priority: duration of sedation infusions, dose of sedation used, level of sedation, incidence of withdrawal from other sedatives, delirium incidence, ICU and hospital length of stay, use and duration of non-invasive ventilation, and all-cause ICU and hospital mortality. We will also capture unwanted effects potentially associated with clonidine administration such as clinically significant hypotension or bradycardia, clonidine withdrawal, self-extubation, and the accidental removal of central intravenous lines and arterial lines. We will not apply any publication date, language, or journal restrictions. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria and then review full reports of all potentially relevant citations. A third reviewer will resolve disagreements if consensus cannot be achieved. We will use Review Manager (RevMan) to pool effect estimates from included studies across outcomes. We will present the results as relative risk (RR) with 95 % confidence intervals (CI) for dichotomous outcomes and as mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95 % CI. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: The aim of this systematic review is to summarize the evidence on the efficacy and safety of clonidine as a sedative agent in the critically ill population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019365. PMID- 26542365 TI - Risk factors for early post-operative neurological deterioration in dogs undergoing a cervical dorsal laminectomy or hemilaminectomy: 100 cases (2002 2014). AB - Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25 64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures. PMID- 26542366 TI - Isolation and characterization of a herpesvirus from feral pigeons in China. AB - A herpesvirus was isolated during a diagnostic investigation of severe cases of conjunctivitis in feral pigeons (Columba livia f. domestica). Isolates of the virus were recovered from throat swabs of the pigeons followed by inoculation of the swab samples in chicken embryo fibroblasts. Pigeons inoculated with the isolated virus had similar clinical signs to those observed in naturally infected birds. Transmission electron microscopy revealed viral structures with typical herpesvirus morphology. Polymerase chain reaction amplification, using herpesvirus-identifying primers resulted in an amplicon of the expected size for herpesvirus. Sequencing of these amplicons and database comparisons identified the herpesvirus UL30 homologue. Phylogenetic reconstructions suggested that the isolated herpesvirus belongs to the Mardivirus genus of Alphaherpesvirinae. Using the current herpesvirus nomenclature conventions, the authors propose that the herpesvirus be named Columbid herpesvirus-1 Heilongjiang. PMID- 26542367 TI - Development of a serological ELISA using a recombinant protein to identify pig herds infected with Brachyspira hyodysenteriae. AB - Brachyspira hyodysenteriae is an anaerobic spirochaete that can induce swine dysentery (SD), a severe mucohaemorrhagic colitis in grower and fattener pigs. The aim of this study was to develop a serological ELISA for use as a screening method to detect evidence of herd infection. Bioinformatic analysis of the complete genome sequence of strain WA1 was used to identify genes predicted to encode outer membrane proteins. Twenty candidate genes were expressed in an Escherichia coli mediated system, and purified as histidine-tagged recombinant proteins. Selection of optimal antigens under different conditions was conducted using Western blot and ELISA with a range of pig sera from infected and uninfected pigs. From this analysis, three recombinant proteins were selected as being most suitable for use as antigens. These antigens then were tested under optimized conditions in an indirect ELISA detecting IgG2 using 1551 sera from healthy pigs at slaughter, comprising 896 from 18 herds considered to be free from SD and 655 from 12 infected herds. Using a cut-off value for positivity of the mean plus five standard deviations of the mean for the negative sera, the best overall results were obtained with the ELISA using antigen H114, which was 100% specific and 91.7% sensitive at detecting the reported status of the herds. This new ELISA should be a useful adjunct for detecting and monitoring the status of herds with respect to the presence of B. hyodysenteriae, and should prove useful for understanding the dynamics of infection in herds where the spirochaete is present. PMID- 26542368 TI - Endocrine tumours in the guinea pig. AB - Functional endocrine tumours have long been thought to be rare in guinea pigs, although conditions such as hyperthyroidism and hyperadrenocorticism have been documented with increasing frequency so the prevalence of hormonal disorders may have been underestimated. Both the clinical signs and diagnosis of hyperthyroidism in guinea pigs appear to be very similar to those described in feline hyperthyroidism, and methimazole has been proven to be a practical therapy option. Hyperadrenocorticism has been confirmed in several guinea pigs with an adrenocorticotropic hormone stimulation test using saliva as a non-invasive sample matrix; trilostane has been successfully used to treat a guinea pig with hyperadrenocorticism. Insulinomas have only rarely been documented in guinea pigs and one animal was effectively treated with diazoxide. PMID- 26542369 TI - Ovarian stem cells are always accompanied by very small embryonic-like stem cells in adult mammalian ovary. AB - BACKGROUND: Existing dogma that a female is born with fixed number of eggs was challenged by the detection of stem cells in adult mammalian ovary. Data has accumulated in support of ovarian stem cells (OSCs) proliferation, maintenance in culture, formation of germ cell nests and differentiation into oocytes and primordial follicle assembly using different strategies. RESULTS: Flow cytometry analysis identified >8 MUm OSCs which are DDX1 positive and are considered equivalent to spermatogonial stem cells (SSCs) in testis. Analysis of both ovarian and testicular smears obtained after enzymatic digestion has led to the identification of an additional stem cell population termed very small embryonic like stem cells (VSELs). VSELs and OSCs/SSCs differ from each other in their size and OCT-4 expression. VSELs express pluripotent markers including nuclear OCT-4 whereas OSCs/SSCs express cytoplasmic OCT-4 suggesting a differentiated state. VSELs can be studied by flow cytometry as small sized cells which are LIN-/CD45 /Sca-1+. We have reported 0.02 +/- 0.008, 0.03 +/- 0.017 and 0.08 +/- 0.03 % of total cells as VSELs in normal, chemoablated and after FSH treatment to chemoablated mouse ovary. CONCLUSIONS: VSELs have remained poorly studied till now because of their very small size and rare occurrence. Spinning cells obtained after enzymatic digestion of ovarian tissue at a speed of 1000G (rather than 1200 rpm) throughout processing allows reliable detection of the VSELs by flow cytometry. VSELs exist in aged, chemoablated and non-functional ovary and providing a healthy niche to support their function offers an interesting strategy to manage infertility. PMID- 26542370 TI - Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress. AB - Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile formation. Mutations in human homologue MDR3 are associated with several liver diseases. Knockout of Mdr2 results in hepatic inflammation, liver fibrosis and hepatocellular carcinoma (HCC). Whereas the pathogenesis in Mdr2 (-/-) mice has been largely attributed to the toxicity of bile acids due to the absence of PC in the bile, the question of whether Mdr2 deficiency per se perturbs biological functions in the cell has been poorly addressed. As Mdr2 is expressed in many cell types, we used mouse embryonic fibroblasts (MEF) derived from Mdr2 (-/-) embryos to show that deficiency of Mdr2 increases reactive oxygen species accumulation, lipid peroxidation and DNA damage. We found that Mdr2 (-/-) MEFs undergo spontaneous transformation and that Mdr2 (-/-) mice are more susceptible to chemical carcinogen-induced intestinal tumorigenesis. Microarray analysis in Mdr2-/- MEFs and cap analysis of gene expression in Mdr2 (-/-) HCCs revealed extensively deregulated genes involved in oxidation reduction, fatty acid metabolism and lipid biosynthesis. Our findings imply a close link between Mdr2 ( /-) -associated tumorigenesis and perturbation of these biological processes and suggest potential extrahepatic functions of Mdr2/MDR3. PMID- 26542371 TI - Comparison of methods for the analysis of airway macrophage particulate load from induced sputum, a potential biomarker of air pollution exposure. AB - BACKGROUND: Air pollution is associated with a high burden or morbidity and mortality, but exposure cannot be quantified rapidly or cheaply. The particulate burden of macrophages from induced sputum may provide a biomarker. We compare the feasibility of two methods for digital quantification of airway macrophage particulate load. METHODS: Induced sputum samples were processed and analysed using ImageJ and Image SXM software packages. We compare each package by resources and time required. RESULTS: 13 adequate samples were obtained from 21 patients. Median particulate load was 0.38 MUm(2) (ImageJ) and 4.0 % of the total cellular area of macrophages (Image SXM), with no correlation between results obtained using the two methods (correlation coefficient = -0.42, p = 0.256). Image SXM took longer than ImageJ (median 26 vs 54 mins per participant, p = 0.008) and was less accurate based on visual assessment of the output images. ImageJ's method is subjective and requires well-trained staff. CONCLUSION: Induced sputum has limited application as a screening tool due to the resources required. Limitations of both methods compared here were found: the heterogeneity of induced sputum appearances makes automated image analysis challenging. Further work should refine methodologies and assess inter- and intra-observer reliability, if these methods are to be developed for investigating the relationship of particulate and inflammatory response in the macrophage. PMID- 26542372 TI - Lifetime expectancy and quality-adjusted life-year in Alzheimer's disease with and without cerebrovascular disease: effects of nursing home replacement and donepezil administration--a retrospective analysis in the Tajiri Project. AB - BACKGROUND: We previously demonstrated a positive correlation with nursing home (NH) replacement and donepezil (DNP) administration on lifetime expectancy after the onset of Alzheimer's disease (AD). However, the correlation with quality adjusted life-year (QALY) remains to be elucidated, along with the additional impact of concomitant cerebrovascular disease (CVD). Based upon our recently reported health state utility values, we retrospectively analyzed the correlation with NH replacement and/or DNP administration on QALY and life expectancy in 'pure' AD (without CVD) and AD with CVD patients. METHODS: All outpatients at the Tajiri Clinic from 1999-2012 with available medical records and death certificates were included. The entry criteria were a dementia diagnosis (DSM-IV) and diagnoses of pure AD or AD with CVD (NINCDS-ADRDA), medical treatment for more than 3 months, and follow up to less than 1 year before death. The main outcomes were lifetime expectancy (months between the onset of dementia and death) and QALY. RESULTS: We identified 390 subjects, of whom 275 had the diagnosis of dementia that met the entry criteria, including 67 pure AD, 33 AD with CVD, and 110 VaD patients. For the AD patients, 52 had taken DNP and 48 had not received the drug due to treatment prior to the introduction of DNP in 1999 in Japan. For the pure AD group, there were positive correlation between NH and DNP and QALY, as well as lifetime expectancy. As for the AD with CVD group, only a correlation between DNP and lifetime expectancy was noted, with no correlation with QALY. CONCLUSIONS: We found positive correlations between DNP administration and NH replacement and lifetime expectancy and QALY after the onset of AD. However, concomitant CVD negated such a positive correlation with QALY. The findings suggest that QALY in AD is affected by CVD; thus, indicating the importance of CVD prevention. PMID- 26542373 TI - Comparison of thoracolaparoscopic esophagectomy with cervical anastomosis with McKeown esophagectomy for middle esophageal cancer. AB - BACKGROUND: In China, the middle esophageal squamous cell cancer is the most common tumor type, and Mckeown esophagectomy (ME) is preferably adopted by thoracic surgeon. But, the surgical trauma of ME is great. Thoracolaparoscopic esophagectomy (TE) was developed to decrease the operative stress; however, the safety and efficacy were not defined. In this study, clinical outcomes were compared between patients who received ME and TE. METHODS: The data of 113 patients who suffered from middle-thoracic esophageal cancer during the same period were collected. Sixty-two patients received ME (ME group), and 51 patients received TE (TE group). Patients' demographics and short-term clinicopathologic outcomes were comparable between the two groups. Survival rate was estimated using the Kaplan-Meier method, and comparisons between groups were performed with log-rank test. RESULTS: Patients in TE group had lower body mass index (BMI). Preoperative tumor stage in TE group was much earlier. Both overall and thoracic operation time were longer in TE group. The blood loss during operation and postoperative day (POD) 1 was less in TE group, which contributed to the less blood transfusion. In TE group, postoperative incidence of pulmonary complications and atrial fibrillation (p = 0.035 and p = 0.033) was lower; the inflammatory response and incision pain were significantly alleviated; the ICU and in-hospital stay was shorter as well because of less surgical trauma. No statistically significant difference was found between two groups in terms of overall survival or disease-free survival. CONCLUSIONS: The efficacy and safety of TE were supported by the selected patients in this cohort study. Although it is lack of randomness in this research, some advantages of TE were gratifying such as lower postoperative complications and similar survival with ME. A multicenter prospective randomized study is now required. PMID- 26542374 TI - Assessment of efficacy and safety of EUS-guided biliary drainage: a systematic review. AB - BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has emerged as an alternative procedure after failed ERCP. However, limited data on the efficacy and safety of EUS-BD are available. Therefore, a systematic review was conducted to evaluate the efficacy and safety of EUS-BD and to evaluate transduodenal (TD) and transgastric (TG) approaches. METHODS: PubMed and EMBASE were searched to identify relevant studies published in the English language for inclusion in this systematic review and meta-analysis. Data from eligible studies were combined to calculate the cumulative technical success rate (TSR), functional success rate (FSR), and adverse-event rate of EUS-BD and the pooled odds ratio of TSR, FSR, and adverse-event rate of the TD approach when compared with the TG approach. RESULTS: Forty-two studies with 1192 patients were included in this study, and the cumulative TSR, FSR, and adverse-event rate were 94.71%, 91.66%, and 23.32%, respectively. The common adverse events associated with EUS-BD were bleeding (4.03%), bile leakage (4.03%), pneumoperitoneum (3.02%), stent migration (2.68%), cholangitis (2.43%), abdominal pain (1.51%), and peritonitis (1.26%). Ten studies were included in the meta-analysis for comparative evaluation of TD and TG approaches for EUS-BD. Compared with the TG approach, the pooled odds ratio of the TSR, FSR, and adverse-event rate of the TD approach were 1.36 (95% CI, .66 2.81; P > .05), .84 (95% CI, .50-1.42; P > .05), and .61 (95% CI, .36-1.03; P > .05), respectively, which indicated no significant difference in the TSR, FSR, and adverse-event rate between the 2 groups. CONCLUSIONS: Although it is associated with significant morbidity, EUS-BD is an effective alternative procedure for relieving biliary obstruction. There was no significant difference between the TD and TG approaches for EUS-BD. PMID- 26542375 TI - Extracorporeal shock wave lithotripsy is a safe and effective treatment for pancreatic stones coexisting with pancreatic pseudocysts. AB - BACKGROUND AND AIMS: We aimed to investigate outcomes of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for the removal of large pancreatic stones coexisting with pancreatic pseudocysts (PPCs) in chronic pancreatitis (CP). METHODS: This is a prospective study performed in CP patients with at least 1 stone (>=5 mm). Patients were divided into the PPC group (stones coexisting with PPCs) or the control group (stones alone). Patients were initially subjected to successive P-ESWL treatments, followed by ERCP. Primary outcomes were P-ESWL adverse events, and secondary outcomes were stone clearance, long-term pain relief, improved quality-of-life scores, and PPC regression. RESULTS: A total of 849 patients (59 in the PPC group and 790 in the control group) was subjected to P-ESWL between March 2011 and October 2013. Occurrences of P-ESWL adverse events were similar between the PPC group and the control group (11.86% vs 12.41%, P = .940). After the treatment of initial P-ESWL combined with ERCP, the complete, partial, and nonclearance of stones occurred in 67.24%, 20.69%, and 12.07%, respectively, of patients in PPC group, with no significant difference from the control group (complete, partial, and nonclearance: 83.17%, 10.40%, and 11.39%, respectively; P = .106). Fifty-five of 59 patients (93.22%) with PPCs were followed for a median period of 21.9 months (range, 12.0-45.1). PPCs disappeared in 56.36% (31/55) and 76.36% (42/55) of patients after 3 months and 1 year of follow-up visits, respectively. Moreover, complete and partial pain relief were achieved in 63.64% (35/55) and 25.45% (14/55) of patients, respectively. The scores for quality of life (P < .001), physical health (P < .001), and weight loss (P < .001) improved. CONCLUSIONS: In our multispecialty tertiary center, initial P-ESWL followed by ERCP was safe in patients with coexisting pancreatic stones and PPCs and effective for stone clearance, main pancreatic duct drainage, and pain relief. PMID- 26542376 TI - Tailoring percolating conductive networks of natural rubber composites for flexible strain sensors via a cellulose nanocrystal templated assembly. AB - Conductive polymer composites (CPCs) just above the percolation threshold exhibit a unique strain-reversible electric response upon application of tensile strain, which can be used to prepare strain sensors. However, it is difficult to balance the electric conductivity which is fundamental to a stable output signal and the strain sensing sensitivity due to the relatively dense conductive pathways of the traditional CPCs. Constructing a "brittle" but effective conductive network structure in CPCs is the essential foundation of a desirable sensing material. Here, we demonstrate for the first time that highly flexible, stretchable, sensitive, and reversible strain sensors can be fabricated by a facile latex assembly approach, in which nontoxic, sustainable and biodegradable cellulose nanocrystals played a key role in tailoring the percolating network of conductive natural rubber (NR)/carbon nanotube (CNT) composites. The resulting nanocomposites with a continuous 3D conductive structure exhibited a very low electrical conductivity percolation threshold (4-fold lower than that of the conventional NR/CNT composites), high resistivity and sensitivity (gauge factor ~ 43.5) and meanwhile good reproducibility of up to 100% strain. The proposed materials and principles in this study open up a novel practical approach to design high performance flexible sensors for a broad range of multifunctional applications. PMID- 26542377 TI - Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. AB - Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-beta, IRS-1, PI3K, Akt, Glut4 and PGC-1alpha that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here. PMID- 26542378 TI - A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. AB - We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non germinal center B-cell diffuse large B-cell lymphoma patients (35%) responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during therapy. One CLL patient experienced a grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT01659255. PMID- 26542379 TI - Associations of psychosocial working conditions and working time characteristics with somatic complaints in German resident physicians. AB - PURPOSE: Somatic complaints (SC) are highly prevalent in working populations and cause suffering and extensive health-care utilization. Adverse psychosocial working conditions as conceptualized in the Job Demand-Control-Support Model (JDC S) and adverse working time characteristics (WTC) are potential risk factors. This combination is particularly common in hospital physicians. This study examines associations of JDC-S and WTC with SC in resident physicians from Germany. METHODS: A cross-sectional study was conducted among 405 physicians at the end of residency training. SC were measured using the Giessen Subjective Complaints List (GBB-24) containing the sub-categories exhaustion, gastrointestinal, musculoskeletal, and cardiovascular complaints. Data on working conditions were collected by a self-report method for work analysis in hospitals (TAA-KH-S) and by questions on WTC (i.e., working hours). Multivariable stepwise regression analyses were applied. RESULTS: Workload showed the most pronounced relationship with all sub-categories of SC except gastrointestinal complaints. Job autonomy was not significantly related to any SC sub-category. Social support at work was inversely associated with all SC sub-categories except for cardiovascular complaints. Free weekends were associated with reduced SC except for exhaustion. Shift work was related to an increased SC total score and musculoskeletal complaints. Working hours showed no association with SC. CONCLUSION: In resident physicians, high workload and shift work are associated with increased SC, while social support at work and free weekends are associated with decreased SC. These insights may inform the development of preventive measures to improve the health of this professional group. Prospective studies are needed though to corroborate our findings. PMID- 26542380 TI - [Association between fat mass index and fat-free mass index values and cardiovascular risk in adolescents]. AB - OBJECTIVE: To describe the association between fat mass index and fat-free mass index values and factors associated with cardiovascular risk in adolescents in the city of Juiz de Fora, Minas Gerais. METHODS: Cross-sectional study with 403 adolescents aged 10-14 years, from public and private schools. Anthropometric, clinical, biochemical measurements were obtained, as well as self-reported time spent performing physical exercises, sedentary activities and sexual maturation stage. RESULTS: Regarding the nutritional status; 66.5% of the adolescents had normal weight; 19.9% were overweight and 10.2% were obese. For both genders, the fat mass index was higher in adolescents that had high serum triglycerides, body mass index and waist circumference. CONCLUSIONS: Adolescents that had anthropometric, clinical and biochemical characteristics considered to be of risk for the development of cardiovascular disease had higher values of fat mass index. Different methodologies for the assessment of body composition make health promotion and disease prevention more effective. PMID- 26542381 TI - Incorporating Long-acting Reversible Contraception Into Primary Care: A Training and Practice Innovation. PMID- 26542382 TI - Exploring Group Composition among Young, Urban Women of Color in Prenatal Care: Implications for Satisfaction, Engagement, and Group Attendance. AB - PURPOSE: Group models of prenatal care continue to grow in popularity. However, little is known about how group composition (similarity or diversity between members of groups) relates to care-related outcomes. The current investigation aimed to explore associations between prenatal care group composition with patient satisfaction, engagement, and group attendance among young, urban women of color. METHODS: Data were drawn from two studies conducted in New Haven and Atlanta (2001-2004; n = 557) and New York City (2008-2011; n = 375) designed to evaluate group prenatal care among young, urban women of color. Women aged 14 to 25 were assigned to group prenatal care and completed surveys during their second and third trimesters of pregnancy. Group attendance was recorded. Data were merged and analyzed guided by the Group Actor-Partner Interdependence Model using multilevel regression. Analyses explored composition in terms of age, race, ethnicity, and language. MAIN FINDINGS: Women in groups with others more diverse in age reported greater patient engagement and, in turn, attended more group sessions, b(se) = -0.01(0.01); p = .04. CONCLUSION: The composition of prenatal care groups seems to be associated with young women's engagement in care, ultimately relating to the number of group prenatal care sessions they attend. Creating groups diverse in age may be particularly beneficial for young, urban women of color, who have unique pregnancy needs and experiences. Future research is needed to test the generalizability of these exploratory findings. PMID- 26542383 TI - The Role of Parity in Gestational Weight Gain and Postpartum Weight Retention. AB - OBJECTIVES: Parity, excessive gestational weight gain (GWG), and postpartum weight retention (PPWR) have been identified as risk factors for maternal obesity. The aim of this study was to explore whether GWG and PPWR at 6 and 12 months after birth differed for primiparous and multiparous Australian women. METHODS: One hundred thirty-eight Australian women provided weight measures in early to mid pregnancy (M = 16.7 weeks, SD = 2.3), late pregnancy (M = 37.7 weeks, SD = 2.4), 6 months postpartum (M = 6.1 months, SD = 1.4), and 12 months postpartum (M = 12.6 months, SD = 0.7). Height, parity, and demographic information were also collected. Prepregnancy body mass index (BMI), total GWG, incidence of excessive GWG, as well as change in BMI and BMI category from prepregnancy to 6 and 12 months postpartum were computed. Differences between primiparous and multiparous women were compared using analysis of covariance (controlling for age, prepregnancy BMI, and GWG) and chi(2) test of independence. RESULTS: Seventy women (50.7%) were primiparous and 68 women (49.3%) were multiparous. Primiparous women were more likely to retain weight at 12 months postpartum than multiparous women (p = .021; Cohen's d = .24). This difference was not reflected when analyzing change in BMI categories from prepregnancy to the postpartum. CONCLUSIONS: Evidence for the role of parity in PPWR is inconclusive. Future research should consider the temporal development of PPWR in primiparous and multiparous women, leading to tailored care in the postpartum period to help women return to a healthy prepregnancy weight. PMID- 26542384 TI - The Role of Patient Activation in Contraceptive Use. AB - PURPOSE: Many unintended pregnancies occur due to to contraceptive misuse and nonuse, which is partly due to to lack of knowledge and low self-efficacy related to contraception. We conducted an exploratory, cross-sectional study among low income women to examine the relationship between knowledge, skills, and confidence in managing one's health, measured using the Patient Activation Measure (PAM) and factors that influence contraceptive use. METHODS: A survey and chart review were conducted among 18- to 45-year-old women from a community health center in Chicago, Illinois, to measure the relationship between activation, self-confidence in avoiding pregnancy, contraception use, and contraceptive counseling. Associations between PAM and outcomes were evaluated using the chi(2) test and adjusted logistic regression models. RESULTS: Among 112 participants (61% Latina, 15% Black, 14% White), we found no differences in PAM by age, race/ethnicity, or parity. Women with higher PAM were more likely to be confident they could avoid pregnancy compared with women with lower PAM (50% vs. 7%; p = .02). Higher PAM remained a significant predictor for self-confidence after risk adjustment (odds ratio, 3.13; 95% CI, 1.11-8.78; p = .031). Greater confidence in avoiding pregnancy was associated with using a moderately or highly effective contraceptive method (43% vs. 14%; p = .047). Women with lower PAM were less likely to receive contraceptive counseling in the prior month (0% vs. 57%; p < .01). CONCLUSIONS: Patient activation may be an important construct for understanding factors that influence women's contraceptive use, including self confidence in avoiding pregnancy until it is desired and receiving contraceptive services in primary care. PMID- 26542385 TI - Superior Electrochemical Properties of Nanofibers Composed of Hollow CoFe2 O4 Nanospheres Covered with Onion-Like Graphitic Carbon. AB - Nanofibers composed of hollow CoFe2 O4 nanospheres covered with onion-like carbon are prepared by applying nanoscale Kirkendall diffusion to the electrospinning process. Amorphous carbon nanofibers embedded with CoFe2 @onion-like carbon nanospheres are prepared by reduction of the electrospun nanofibers. Oxidation of the CoFe2 -C nanofibers at 300 degrees C under a normal atmosphere produces porous nanofibers composed of hollow CoFe2 O4 nanospheres covered with onion-like carbon. CoFe2 nanocrystals are transformed into the hollow CoFe2 O4 nanospheres during oxidation through a well-known nanoscale Kirkendall diffusion process. The discharge capacities of the carbon-free CoFe2 O4 nanofibers composed of hollow nanospheres and the nanofibers composed of hollow CoFe2 O4 nanospheres covered with onion-like carbon are 340 and 930 mA h g(-1) , respectively, for the 1000th cycle at a current density of 1 A g(-1) . The nanofibers composed of hollow CoFe2 O4 nanospheres covered with onion-like carbon exhibit an excellent rate performance even in the absence of conductive materials. PMID- 26542386 TI - Erratum to: MONALISA for stochastic simulations of Petri net models of biochemical systems. PMID- 26542387 TI - First results of automated RAPD-SWIFT method in dynamic pupillometry. AB - BACKGROUND: This paper presents preliminary observations on the use of a commercial pupillometric instrument (Albomed PupilX) for the detection and quantification of Relative Afferent Pupillary Defect (RAPD). In this pilot study, video-based pupillometry was used in conjunction with calibrated LED illumination to simulate the effects of the traditional swinging-flashlight test using neutral density filters. METHODS: The results presented in this study follow a method described by Wilhelm et al. (Tubingen SWIFT-test) in which the eyes are illuminated alternately and the response in pupil diameter measured by video pupillometry. Using the PupilX instrument, the LED intensity can be programmed in logarithmic steps starting from a maximum intensity of 1000 lux (lx), with each reduction of 50% in illumination intensity corresponding to a 0.3 log-units increase in filter density. RESULTS: The eyes were stimulated unilaterally with illumination intensities corresponding to a neutral density range of 0.0 to 0.9 log-units. In all normal subjects a symmetrical pupil reaction was seen, independent of which eye was stimulated. In contrast, in a subject with known RAPD, a clear asymmetry in the reaction to stimulation of the left and the right eyes was seen. CONCLUSIONS: These measurements were compared with typical results from the original Tubingen SWIFT study and good qualitative agreement was seen. Furthermore, the method can clearly differentiate between healthy subjects and those with a known RAPD, indicating that the PupilX, programmed with specific stimulus sequences and in conjunction with a suitable analysis software, has the potential for recognition and quantification of RAPD, and prompting the suggestion for further study involving a range of patients including both normal subjects and those with a known and quantified RAPD. PMID- 26542388 TI - Design of a multi-arm randomized clinical trial with no control arm. AB - BACKGROUND: Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. METHODS/DESIGN: For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. RESULTS: We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. CONCLUSION: Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. PMID- 26542389 TI - The intervention composed of aerobic training and non-exercise physical activity (I-CAN) study: Rationale, design and methods. AB - Recent data has suggested that prolonged sedentary behavior is independent risk factor for cardiovascular and all-cause mortality independent of adequate amounts of moderate to vigorous physical activity. However, few studies have prospectively evaluated if exercise training and increasing non-exercise physical activity leads to greater reduction in cardiometabolic risk compared to aerobic training alone. The purpose of the Intervention Composed of Aerobic Training and Non-Exercise Physical Activity (I-CAN) study is to determine whether a physical activity program composed of both aerobic training (consistent with public health recommendations) and increasing non-exercise physical activity (3000 steps above baseline levels) leads to enhanced improvements in waist circumference, oral glucose tolerance, systemic inflammation, body composition, and fitness compared to aerobic training alone in obese adults (N=45). Commercially available accelerometers (Fitbits) will be used to monitor physical activity levels and behavioral coaching will be used to develop strategies of how to increase non exercise physical activity levels. In this manuscript, we describe the design, rationale, and methodology associated with the I-CAN study. PMID- 26542390 TI - Long-term recurrence rates after the removal of spinal meningiomas in relation to Simpson grades. AB - PURPOSE: Simpson grade II removal (coagulation of the dural attachment after gross total removal) of spinal meningioma is considered an acceptable alternative, but increased recurrence after more than 10 years has been reported. More attention must be paid to the long-term surgical outcomes after Simpson grade II removal. METHODS: A retrospective review was performed for 20 patients (M:F = 5:15; age, 59 +/- 9 years) with Simpson grade II removal (mean follow-up period, 12.9 years; range 10.0-17.5). Magnetic resonance (MR) imaging was conducted in 17 patients at 88 +/- 52 months (range 12-157). During the same period, Simpson grade I removal (removal of the dural origin) was performed in 21 patients (follow-up, 89 +/- 87 months; range 9-316). Radiological recurrence was defined as a visible tumor on a follow-up MR image, and clinical tumor recurrence was defined as the recurrence of symptoms. RESULTS: At the final follow-up, neurological symptoms had improved in 16/20 patients and remained stable in 4/20. A recurrent tumor was detected in one patient due to increased back pain at 92 months postoperative, but the symptom was stable without surgery until the last follow-up (124 months). The radiological and clinical recurrence-free survival periods were 150 +/- 7 months (95 % CI 136-163) and 204 +/- 6 months (95 % CI 193 215), respectively. There was no recurrence after Simpson grade I removal, whereas neurological deterioration occurred in two patients after surgery. CONCLUSIONS: Simpson grade II removal may be an alternative option if the risk of complications with Simpson grade I removal is expected to be high. PMID- 26542391 TI - Aggressive bougie dilatation and intralesional steroids is effective in refractory benign esophageal strictures secondary to corrosive ingestion. AB - Endoscopic dilatation of corrosive esophageal strictures is effective, but some patients are refractory to it and require long-term repeated dilatations. The present study was carried out to analyze whether rigorous schedule of endoscopic bougie dilatation along with intralesional injection of triamcinolone in patients refractory to endoscopic dilatation alone could decrease the number and frequency of endoscopic dilatations. The inclusion criterion for this prospective study was patients with refractory corrosive esophageal stricture of any age group. Refractory benign esophageal stricture is defined as an anatomic fibrotic esophageal restriction with inability to achieve dilatation of >=14 mm or to maintain dilatation for 4 weeks once >=14 mm diameter is achieved. The patients were followed up prospectively for 1 year. Patients with refractory strictures were subjected to weekly bougie dilatation (Savary-Gilliard) of the strictures along with injections of intralesional triamcinolone (40 mg/mL, 1 mL diluted in 1 mL of saline, 0.5 mL injected per quadrant of stricture) for consecutive 5 weeks, referred to as rigorous schedule. Further dilatation was done on an 'on-demand' basis. Eleven patients were enrolled for the study. Dysphagia score improved from pre-intervention score of 3.54 +/- 0.52 to 0.45 +/- 0.52 post-intervention (P < 0.001). The maximum dilatation achieved pre-intervention was 9.90+1.04 mm Savary Gilliard and post-intervention significantly improved to 14.7 + 0.7 mm Savary Gilliard (P < 0.001). The periodic dilatation index defined as number of dilatations per month also significantly improved from pre-intervention score of 2.54 +/- 1.06 to post-intervention score of 0.19 + 0.13 (P < 0.001). No adverse effects were reported by the patients. Rigorous weekly schedule of bougie dilatation and intralesional triamcinolone in combination is safe and effective in achieving significant dilatation, reducing the frequency dilatations, maintaining dilatation and improving dysphagia till 1 year of follow-up. PMID- 26542394 TI - A study of waste liquid crystal display generation in mainland China. AB - The generation of liquid crystal display waste is becoming a serious social problem. Predicting liquid crystal display waste status is the foundation for establishing a recycling network; however, the difficulty in predicting liquid crystal display waste quantity lies in data mining. In order to determine the quantity and the distribution of liquid crystal display waste in China, the four top-selling liquid crystal display products (liquid crystal display TVs, desktop PCs, notebook PCs, and mobile phones) were selected as study objects. Then, the extended logistic model and market supply A method was used to predict the quantity of liquid crystal display waste products. Moreover, the distribution of liquid crystal display waste products in different regions was evaluated by examining the consumption levels of household equipment. The results revealed that the quantity of waste liquid crystal displays would increase rapidly in the next decade. In particular, the predicted quantity of waste liquid crystal displays would rise to approximately 4.262 * 10(9) pieces in 2020, and the total display area (i.e. the surface area of liquid crystal display panels) of waste liquid crystal displays would reach 5.539 * 10(7) m(2). The prediction on the display area of waste liquid crystal display TVs showed that it would account for 71.5% of the total display area by 2020. Meanwhile, the quantity of waste mobile phones would significantly grow, increasing 5.8 times from 2012 to 2020. In terms of distribution, Guangdong is the top waste liquid crystal display-generating province in China, followed by Jiangsu, Shandong, Henan, Zhejiang, and Sichuan. Considering its regional characteristics, Guangdong has been proposed to be the most important location of the recycling network. PMID- 26542393 TI - Endophytic Epichloe species and their grass hosts: from evolution to applications. AB - The closely linked fitness of the Epichloe symbiont and the host grass is presumed to align the coevolution of the species towards specialization and mutually beneficial cooperation. Ecological observations demonstrating that Epichloe-grass symbioses can modulate grassland ecosystems via both above- and belowground ecosystem processes support this. In many cases the detected ecological importance of Epichloe species is directly or indirectly linked to defensive mutualism attributable to alkaloids of fungal-origin. Now, modern genetic and molecular techniques enable the precise studies on evolutionary origin of endophytic Epichloe species, their coevolution with host grasses and identification the genetic variation that explains phenotypic diversity in ecologically relevant characteristics of Epichloe-grass associations. Here we briefly review the most recent findings in these areas of research using the present knowledge of the genetic variation that explains the biosynthetic pathways driving the diversity of alkaloids produced by the endophyte. These findings underscore the importance of genetic interplay between the fungus and the host in shaping their coevolution and ecological role in both natural grass ecosystems, and in the agricultural arena. PMID- 26542392 TI - Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies. AB - A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis induction of necrotic TB lesions in the lungs-and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials. PMID- 26542395 TI - PKCalpha regulates TMEM16A-mediated Cl- secretion in human biliary cells. AB - TMEM16A is a newly identified Ca(2+)-activated Cl(-) channel in biliary epithelial cells (BECs) that is important in biliary secretion. While extracellular ATP stimulates TMEM16A via binding P2 receptors and increasing intracellular Ca(2+) concentration ([Ca(2+)]i), the regulatory pathways have not been elucidated. Protein kinase C (PKC) contributes to ATP-mediated secretion in BECs, although its potential role in TMEM16A regulation is unknown. To determine whether PKCalpha regulates the TMEM16A-dependent membrane Cl(-) transport in BECs, studies were performed in human biliary Mz-cha-1 cells. Addition of extracellular ATP induced a rapid translocation of PKCalpha from the cytosol to the plasma membrane and activation of whole cell Ca(2+)-activated Cl(-) currents. Currents demonstrated outward rectification and reversal at 0 mV (properties consistent with TMEM16A) and were inhibited by either molecular (siRNA) or pharmacologic (PMA or Go6976) inhibition of PKCalpha. Intracellular dialysis with recombinant PKCalpha activated Cl(-) currents with biophysical properties identical to TMEM16A in control cells but not in cells after transfection with TMEM16A siRNA. In conclusion, our studies demonstrate that PKCalpha is coupled to ATP-stimulated TMEM16A activation in BECs. Targeting this ATP-Ca(2+)-PKCalpha signaling pathway may represent a therapeutic strategy to increase biliary secretion and promote bile formation. PMID- 26542396 TI - Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium. AB - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 ( ) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID- 26542398 TI - Novel tactics for neuroprotection in Parkinson's disease: Role of antibiotics, polyphenols and neuropeptides. AB - Parkinson's disease is a progressive neurodegenerative disorder characterized by the degeneration of midbrain nigral dopaminergic neurons. Although its etiology remains unknown, the pathological role of several factors has been highlighted, namely oxidative stress, neuroinflammation, protein misfolding, and mitochondrial dysfunction, in addition to genetic predispositions. The current therapy is mainly symptomatic with l-DOPA aiming to replace dopamine. Novel therapeutic approaches are being investigated with the intention of influencing pathways leading to neuronal death and dysfunction. The present review summarizes three novel approaches, the use of which is promising in pre-clinical studies. Polyphenols have been shown to possess neuroprotective properties on account of their well-established antioxidative and anti-inflammatory actions but also due to their influence on protein misfolding and mitochondrial homeostasis. Within the amazing ancillary effects of antibiotics, their neuroprotective properties against neurodegenerative and neuroinflammatory processes are of great interest for the development of effective therapies against Parkinson's disease. Experimental evidence supports the potential of antibiotics as neuroprotective agents, being useful not only to prevent the formation of toxic alpha-synuclein oligomers but also to ameliorate mitochondrial dysfunction and neuroinflammation. Neuropeptides offer another approach with their diverse effects in the nervous system. Among them, pituitary adenylate cyclase-activating polypeptide, a member of the secretin/glucagon superfamily, has several advantageous effects in models of neurodegeneration, namely anti-apoptotic, anti-inflammatory and antioxidant actions, the combination of which offers a potent protective effect in dopaminergic neurons. Owing to their pleiotropic modes of action, these novel therapeutic candidates have potential in tackling the multidimensional features of Parkinson's disease. PMID- 26542397 TI - Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP. AB - Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic beta-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway. PMID- 26542399 TI - Long-term outcomes of nasopharyngectomy using partial maxillectomy approach. AB - OBJECTIVES/HYPOTHESIS: To determine the long-term outcomes of a prospective cohort of 20 patients who had nasopharyngectomy using an open partial maxillectomy approach. METHOD: A prospective cohort study of the surgical outcomes of patients with recurrent T1 (rT1) and rT2 nasopharyngeal carcinoma recurrence. RESULTS: There were 14 male and six female patients. The mean age was 49 years. The mean duration of follow-up was 60.4 months. All of the surgical margins were free of malignancy. Ten patients (50%) developed recurrences. The 5 year local control rate, disease-free, disease-specific, and overall survivals were 70%, 48.9%, 70.2%, and 66.7%, respectively. There were no major intraoperative complications. The most common morbidity was pain. The median length of hospitalization was 4 days. CONCLUSION: Early local recurrence of nasopharyngeal carcinoma can be treated surgically using a partial maxillectomy approach. The long-term outcomes are similar to nasopharyngectomy performed using the more common approaches. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1103-1107, 2016. PMID- 26542401 TI - Age-related inhibitory deficit, or lack of familiarity benefit? Evidence from letter identification among visual distractors. AB - Age-related deficits in processing complex visual scenes are often attributed to age-related declines in the cognitive abilities required for such tasks. For example, poorer or slower performance of a complex task in the presence of distractor items is often attributed to an age-related deficit in the ability to inhibit the processing of irrelevant information. To investigate the relative contributions of sensory and cognitive factors in such tasks, younger and older participants were asked to identify a letter presented simultaneously with distractors that were either other letters, pieces of letters, or visual noise controls with identical spatial frequency content or contrast profile. In Experiment 1, older adults performed much worse than younger adults when the masking field consisted of other letters. Surprisingly-and contrary to the predictions of inhibitory deficit or visual "pop-out" phenomena-this effect emerged because younger adults performed much better with letter-containing maskers than with any other type of masker, whereas older adults did not. Experiment 2 revealed that age-related changes in the time required to process the visual display do not appear to account for this effect. In Experiment 3, however, we replicated older adults' task performance in a younger adult sample by filtering the experimental stimuli to match the image contrast typically experienced by an older adult. The results of Experiment 3 suggest that age related differences in task performance amidst distractors can emerge from age related declines in contrast sensitivity, which set older adults up to fail at tasks in which younger adults may typically be able to benefit from the familiarity of the target and surrounding objects. PMID- 26542400 TI - Effect of explicit dimensional instruction on speech category learning. AB - Learning nonnative speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is underweighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height, resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies and enhanced perceptual selectivity along the previously underweighted pitch direction dimension. PMID- 26542402 TI - Perception and the strongest sensory memory trace of multi-stable displays both form shortly after the stimulus onset. AB - We investigated the relation between perception and sensory memory of multi stable structure-from-motion displays. The latter is an implicit visual memory that reflects a recent history of perceptual dominance and influences only the initial perception of multi-stable displays. First, we established the earliest time point when the direction of an illusory rotation can be reversed after the display onset (29-114 ms). Because our display manipulation did not bias perception towards a specific direction of illusory rotation but only signaled the change in motion, this means that the perceptual dominance was established no later than 29-114 ms after the stimulus onset. Second, we used orientation selectivity of sensory memory to establish which display orientation produced the strongest memory trace and when this orientation was presented during the preceding prime interval (80-140 ms). Surprisingly, both estimates point towards the time interval immediately after the display onset, indicating that both perception and sensory memory form at approximately the same time. This suggests a tighter integration between perception and sensory memory than previously thought, warrants a reconsideration of its role in visual perception, and indicates that sensory memory could be a unique behavioral correlate of the earlier perceptual inference that can be studied post hoc. PMID- 26542403 TI - Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice. AB - Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)-inducible manner [Tat(+)], their Tat(-) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(-)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(-)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence. PMID- 26542404 TI - [Septic endoprosthesis exchange : Preoperative diagnosis and reimplantation]. AB - BACKGROUND: The treatment of prosthetic joint infection (PJI) is truly challenging. Patients with infected arthroplasty face physical and psychosocial problems. Furthermore, treatment costs represent a tremendous socioeconomic burden. AIM: This article presents an overview of the preoperative diagnosis of PJI and one- or two-stage endoprosthetic exchange options. METHOD: A selective literature search was performed focusing on diagnostics and innovative surgical treatment concepts in PJI. RESULTS: The identification of the underlying pathogen is still the main focus in the diagnosis of PJI. State-of-the-art therapy for PJI with mature biofilm consists of implant removal with one- or two-stage exchange arthroplasty. One-stage exchange offers lower morbidity and improved functional outcome, whereas a two-stage procedure is, according to current knowledge, more favourable in terms of infection control. The novel short-term two-stage exchange regimen combines the advantages of both possibilities. DISCUSSION: Prosthetic joint infection represents a significant challenge for the othopaedic surgeon. Novel treatment options can help to improve outcome and lower the costs to the health care system. PMID- 26542405 TI - [Antimicrobial prosthesis coatings]. AB - BACKGROUND: Antimicrobial coatings have a great potential in the treatment and prevention of periprosthetic joint infection. OBJECTIVE: To present established and novel concepts of antimicrobial coatings. METHODS: A literature review and discussion of published concepts in basic research, pre-clinical animal studies, and clinical practice were carried out. RESULTS: To date there has been a wide range of technical solutions (anti-adhesive surfaces, bioactive surfaces with antimicrobial effects, surfaces releasing antimicrobial substances, nanostructures, bioactive surfaces affecting biofilm development) demonstrating a high potential in pre-clinical studies. Only a few with the bactericidal activity of silver ions have been prepared for the market. Conclusive results with regard to biocompatibility and toxicity are lacking. DISCUSSION: Despite the great potential of antimicrobial coatings, no conclusive decisions can be made because of the limited data and the lack of evidence of their clinical efficacy on the basis of prospective controlled clinical studies. In addition to their unlimited biocompatibility, innovative concepts have to be feasible in everyday clinical routine. PMID- 26542406 TI - [Synovial biomarkers for differential diagnosis of painful arthroplasty]. AB - BACKGROUND: The diagnosis and treatment of periprosthetic joint infection (PJI) remain true clinical challenges. PJI diminishes therapeutic success, causes dissatisfaction for the patient and medical staff, and often requires extensive surgical revision(s). At the present time, an extensive multimodal algorithmic approach is used to avoid time- and cost-consuming diagnostic aberrations. However, especially in the case of the frequent and clinically most relevant "low grade" PJI, the current diagnostic "gold standard" has reached its limits. EVALUATION: Synovial biomarkers are thought to close this diagnostic gap, hopefully enabling the safe differentiation among aseptic, (chronic) septic, implant allergy-related and the arthrofibrotic genesis of symptomatic arthroplasty. Therefore, joint aspiration for obtaining synovial fluid is preferred over surgical synovial tissue biopsy because of the faster results, greater practicability, greater patient safety, and lower costs. In addition to the parameters synovial IL-6, CRP, and leukocyte esterase, novel biomarkers such as antimicrobial peptides and other proinflammatory cytokines are currently highlighted because of their very high to excellent diagnostic accuracy. CONCLUSION: Independent multicenter validation studies are required to show whether a set of different innovative synovial fluid biomarkers rather than a few single parameters is favorable for a safe "one-stop shop" differential diagnosis of PJI. PMID- 26542407 TI - [Orthopaedic implant-associated infections: Update of antimicrobial therapy]. AB - In infections related to prosthetic joints and internal fixation devices, microorganisms adhere as biofim on the surface of the implant. Biofilms are not only resistant to phagocytosis, but also to most antimicrobial agents. Therefore, spontaneous cure does never occur, and antibiotics have to be given for several months. According to traditional concepts, removal of all foreign material was considered as prerequisite for cure. Yet, during the last decades, it has been shown that staphylococcal biofilms can be eliminated by rifampin combination therapy, and Gram-negative biofilms by fluoroquinolones. However, reliable biofilm elimination is only possible, if the duration of infection does not exceed 3-4 weeks. Correct total duration of the antimicrobial therapy has never been tested in a controlled trial. Currently, treatment duration is 3 (hip prosthesis) and 6 (knee prosthesis) months in patients undergoing debridement with implant retention, one-stage exchange, and two-stage exchange with a short interval of 2-3 weeks. According to a recent observational trial, a treatment duration of 2 and 3 months, respectively, is equivalent to the longer duration in patients undergoing debridement and implant retention. The optimal surgical therapy should be chosen according to a rational algorithm. It is crucial choosing the optimal surgical intervention from the beginning, because the final functional success depends on the cure by the first attempt. PMID- 26542408 TI - The Development and Validation of the Comprehensive Intellectual Humility Scale. AB - A series of studies was conducted to create the 22-item Comprehensive Intellectual Humility Scale on the basis of theoretical descriptions of intellectual humility, expert reviews, pilot studies, and exploratory and confirmatory factor analyses. The scale measures 4 distinct but intercorrelated aspects of intellectual humility, including independence of intellect and ego, openness to revising one's viewpoint, respect for others' viewpoints, and lack of intellectual overconfidence. Internal consistency and test-retest analyses provided reliable scale and subscale scores within numerous independent samples. Validation data were obtained from multiple, independent samples, supporting appropriate levels of convergent, discriminant, and predictive validity. The analyses suggest that the scale has utility as a self-report measure for future research. PMID- 26542409 TI - [Recurrent microdislocation of pacemaker leads due to an aortic aneurysm of the aorta ascendens]. AB - We report about a 79 years old female patient which was admitted due to a symptomatic AV block 3rd degree. The coronary angiography excluded a coronary artery disease and the echocardiography revealed a normal left ventricular systolic function. Therefore a dual-chamber pacemaker was implanted. Following two micro-dislocations of the right ventricular lead, which required operative revisions, a computed tomography of the heart was performed. This detected an aneurysm of the ascending aorta (5 cm maximum diameter) with compression of the superior caval vein. This case shows that a possible cause of recurrent micro dislocations could be a pathological anatomy of the heart. PMID- 26542410 TI - Giant extragenital Bowen's disease. AB - Giant extragenital forms of Morbus Bowen are extremely rare. The already described cases in the word literature are most commonly with periungual localization, as well as located on the foot and neck area. The clinical manifestation is presented most commonly by non-specific erythematous to erythematous-squamous plaques or papules, which is confusing to the clinician. From the pathogenic point of view, it is important to be confirmed or rejected the presence of human papilloma viruses (HPVs) in each case of affected patient, as this information is mandatory in respect to the adequate selection of the subsequent regimen. If HPVs are detected, systemic antiviral therapy could be initiated to reduce the size of the lesions before subsequent surgical eradication. A postoperative prevention through vaccination could be also considered additionally. In cases of HPV-negative giant extragenital forms of Morbus Bowen (as in the described patient), the focus should be on local immunomodulation by substances such as imiquimod, which reduce the size of the lesions, thereby creating optimal opportunities for their future surgical eradication. Other possible options described in the literature include topical application of 5-fluorouracil, photodynamic therapy, cryotherapy, and laser therapy (carbon dioxide laser). The choice of the most appropriate regimen should have been an individual decision of the clinician, considering also the location and the extent of the lesion. PMID- 26542411 TI - Feasibility and acceptance of biofeedback-assisted mental training in an Austrian elementary school: a pilot study. AB - This pilot study aimed to investigate feasibility, acceptance, and effects of biofeedback-assisted mental training in a population of fifteen 10-year-old pupils in an Austrian elementary school. Participants were instructed in relaxation techniques by using biofeedback. Before intervention, after 6 weeks with active mental training and with regular instructions by the teacher, and after a further time period of 6 weeks without instructions, attention and concentration improved. The results indicate feasibility, good acceptance, and beneficial effects of biofeedback-assisted mental techniques in Austrian elementary school pupils. PMID- 26542412 TI - A method for estimating spikelet number per panicle: Integrating image analysis and a 5-point calibration model. AB - Spikelet number per panicle (SNPP) is one of the most important yield components used to estimate rice yields. The use of high-throughput quantitative image analysis methods for understanding the diversity of the panicle has increased rapidly. However, it is difficult to simultaneously extract panicle branch and spikelet/grain information from images at the same resolution due to the different scales of these traits. To use a lower resolution and meet the accuracy requirement, we proposed an interdisciplinary method that integrated image analysis and a 5-point calibration model to rapidly estimate SNPP. First, a linear relationship model between the total length of the primary branch (TLPB) and the SNPP was established based on the physiological characteristics of the panicle. Second, the TLPB and area (the primary branch region) traits were rapidly extracted by developing image analysis algorithm. Finally, a 5-point calibration method was adopted to improve the universality of the model. The number of panicle samples that the error of the SNPP estimates was less than 10% was greater than 90% by the proposed method. The estimation accuracy was consistent with the accuracy determined using manual measurements. The proposed method uses available concepts and techniques for automated estimations of rice yield information. PMID- 26542413 TI - Access to transportation for Chittenden County Vermont older adults. AB - BACKGROUND: Aging often leads to decreased independence and mobility, which can be detrimental to health and well-being. The growing population of older adults will create a greater need for reliable transportation. AIMS: Explore whether and how lack of transportation has compromised areas of daily lives in older adults. METHODS: 1221 surveys with 36 questions assessing transportation access, usage, and impact on activities were distributed to Chittenden County, Vermont older adults; 252 met criteria for analysis. RESULTS: Older adults reported overwhelming difficulty getting to activities considered important, with 69 % of participants delaying medical appointments due to transportation barriers. Although family and friends represent a primary method of transportation, older adults reported difficulty asking them for help. DISCUSSION: Lack of accessible transportation leads to missed healthcare appointments and social isolation, which may have detrimental effects on older adults' quality of life. CONCLUSION: Many older adults face significant transportation challenges that negatively affect their health and well-being. PMID- 26542414 TI - Gender differences in the association of hypertension with gamma glutamyltransferase and alanine aminotransferase levels in Chinese adults in Qingdao, China. AB - The aim of the study was to study the associations of hypertension with gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels. Data of 3575 men and 5504 women were analyzed. Multivariate logistic regression analysis was performed to estimate the odds ratio (OR) for hypertension with GGT and ALT. Compared with the lowest quartile, the multivariate adjusted ORs for hypertension were 0.97 (0.79, 1.19) in men and 0.88 (0.74, 1.04) in women for ALT and 2.29 (1.68, 3.14) and 1.52 (1.27, 1.83) for GGT in the highest quartile group. The ORs for hypertension in the low waist circumference category were 2.61 (1.56, 4.36) in men and 1.41 (0.94, 2.12) in women and in the high waist circumference category 4.01 (2.21, 7.29) and 2.26 (1.54, 3.32) for GGT. The elevated GGT, but not ALT, was associated with the presence of the hypertension in men and women. The association is stronger in obese men and women than in their lean counterparts. PMID- 26542415 TI - The path to prevention and treatment of resistant hypertension. PMID- 26542416 TI - CHFR hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome. AB - The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction. In addition, we analyzed possible association between CHFR hypermethylation and hematological characteristics, chromosome abnormalities, genetic mutations, and survival. Hypermethylation of the CHFR promoter was observed in 24% (85 of 358) AML patients, but not in healthy individuals. CHFR hypermethylation correlated significantly with SRSF2 and DNMT3A mutations. Patients with hypermethylation exhibited lower overall survival and shorter relapse-free survival than nonmethylated cases. In multivariate analysis, CHFR hypermethylation was an independent factor predicting poor overall survival but not relapse-free survival. In conclusion, hypermethylation of the CHFR promoter, frequent in AML, is associated with adverse outcome, and can thus be used for risk stratification. PMID- 26542417 TI - Stem cell therapies for traumatic brain injury. PMID- 26542418 TI - Food-alcohol competition: As young females eat more food, do they drink less alcohol? AB - Seminal health behaviour theories and behaviour modification techniques are applied to health behaviours individually. Limited empirical work investigates how change in one health behaviour may change another. This study proposes a food alcohol competition hypothesis, where individuals tend to consume one rewarding substance to the other's exclusion. In a large sample of adolescent girls assessed yearly from age 15 to 19, Latent Growth Modelling indicated that a tendency to consume processed or sweet high-fat foods 'competed' with a tendency to drink alcohol. In order to best improve overall health, it is important to consider interrelationships between food and alcohol consumption. PMID- 26542419 TI - Effects of antenatal exercise in overweight and obese pregnant women on maternal and perinatal outcomes: a randomised controlled trial. AB - OBJECTIVE: To assess whether antenatal exercise in overweight/obese women would improve maternal and perinatal outcomes. DESIGN: Two-arm parallel randomised controlled trial. SETTING: Home-based intervention in Auckland, New Zealand. POPULATION AND SAMPLE: Pregnant women with body mass index >=25 kg/m(2) . METHODS: Participants were randomised to a 16-week moderate-intensity stationary cycling programme from 20 weeks of gestation, or to a control group with no exercise intervention. MAIN OUTCOME MEASURES: Primary outcome was offspring birthweight. Perinatal and maternal outcomes were assessed, with the latter including weight gain, aerobic fitness, quality of life, pregnancy outcomes, and postnatal body composition. Exercise compliance was recorded with heart rate monitors. RESULTS: Seventy-five participants were randomised in the study (intervention 38, control 37). Offspring birthweight (adjusted mean difference 104 g; P = 0.35) and perinatal outcomes were similar between groups. Aerobic fitness improved in the intervention group compared with controls (48.0-second improvement in test time to target heart rate; P = 0.019). There was no difference in weight gain, quality of life, pregnancy outcomes or postnatal maternal body composition between groups. However, compliance with exercise protocol was poor, with an average of 33% of exercise sessions completed. Sensitivity analyses showed that greater compliance was associated with improved fitness (increased test time (P = 0.002), greater VO2 peak (P = 0.015), and lower resting heart rate (P = 0.014)), reduced postnatal adiposity (reduced fat mass (P = 0.007) and body mass index (P = 0.035)) and better physical quality of life (P = 0.034). CONCLUSIONS: Maternal non-weight-bearing moderate-intensity exercise in pregnancy improved fitness but did not affect birthweight or clinical outcomes. TWEETABLE ABSTRACT: Moderate-intensity exercise in overweight/obese pregnant women improved fitness but had no clinical effects. PMID- 26542420 TI - The Effectiveness of Functional Family Therapy in Reducing Adolescent Mental Health Risk and Family Adjustment Difficulties in an Irish Context. AB - To evaluate the effectiveness of Functional Family Therapy (FFT) 42 cases were randomized to FFT and 55 to a waiting-list control group. Minimization procedures controlled the effects of potentially confounding baseline variables. Cases were treated by a team of five therapists who implemented FFT with a moderate degree of fidelity. Rates of clinical recovery were significantly higher in the FFT group than in the control group. Compared to the comparison group, parents in the FFT group reported significantly greater improvement in adolescent problems on the Strengths and Difficulties Questionnaire (SDQ) and both parents and adolescents reported improvements in family adjustment on the Systemic Clinical Outcomes and Routine Evaluation (SCORE). In addition, 93% of youth and families in the treatment condition completed FFT. Improvements shown immediately after treatment were sustained at 3-month follow-up. Results provide a current demonstration of FFT's effectiveness for youth with behavior problems in community-based settings, expand our understanding of the range of positive outcomes of FFT to include mental health risk and family-defined problem severity and impact, and suggests that it is an effective intervention when implemented in an Irish context. PMID- 26542421 TI - The influence of number of line pairs in digital intra-oral radiography on the detection accuracy of horizontal root fractures. AB - AIM: Line pairs are the unit for measurement of resolution and are related to the spatial quality of the system. Thus, the objective of this study was to evaluate the influence of number of line pairs in digital intra-oral radiography on the detection accuracy of horizontal root fractures. MATERIALS AND METHODS: Sixty four extracted single-root human teeth were used. Thirty-two had horizontal root fractures created and were mounted in dry human mandibles. The teeth were radiographed with two digital receptors: the Digora Optime (14.3 lp mm-1) and the Digora Toto (26.3 lp mm-1). Images were viewed under standardized conditions by 3 calibrated examiners using the respective dedicated software (Digora for Windows 2.6((r)) and Scanora((r)) ). Digora Toto((r)) images were also evaluated through the Digora for Windows 2.6((r)) software. The results were statistically analyzed based on the area under the ROC curve for each examiner. RESULTS: Pairing Digora Toto((r)) with Scanora((r)) allowed for greater accuracy in horizontal root fractures diagnosis, while images acquired with that same system seem to lose accuracy when visualized with Digora for Windows 2.6((r)) . Pairing Digora Optime((r)) with Digora for Windows 2.6((r)) resulted in the lowest accuracy for horizontal root fractures diagnosis. CONCLUSIONS: The higher number of line pairs and the consequent higher image resolution provided by the Digora Toto((r)) system and its dedicated software seem to enhance the accuracy of horizontal root fractures diagnostic imaging. PMID- 26542423 TI - Liposarcomatous differentiation in malignant phyllodes tumours is unassociated with MDM2 or CDK4 amplification. AB - AIMS: Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification. METHODS AND RESULTS: We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4. CONCLUSIONS: This study examined molecular changes in the well-differentiated liposarcomatous components of MPT. Despite histological similarity to well-differentiated liposarcoma of soft tissues, liposarcomatous differentiation in MPT lacks the molecular phenotype characteristic of extramammary well-differentiated liposarcoma. PMID- 26542424 TI - Backbone and side-chain NMR assignments for the bromodomain of mouse BAZ1A (ACF1). AB - BAZ1A, a non-catalytic subunit of the chromatin remodeler complexes ACF and CHRAC, is thought to modulate the ATPase's activity of the complexes and participate in gene transcription, DNA damage checkpoint and double-strand break repair. Recently, the essential role of BAZ1A in mouse male fertility has also been reported. BAZ1A contains one C-terminal bromodomain, which specifically recognizes acetylation of lysine. Here, we report the backbone and side chain (1)H, (13)C and (15)N resonance assignment of the mouse BAZ1A-bromodomain, as a basis for further functional studies and structure determination. PMID- 26542422 TI - Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders. AB - Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among 'SS' homozygotes (p = 0.002) but not among 'L' allele carriers. A history of at least one trauma decreased the AAO only in 'SS' homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and 'SS' genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and 'LS' genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype. PMID- 26542426 TI - Letter from the guest editors: pitfalls in abdominal imaging: part 1. PMID- 26542425 TI - PredyCLU: a prediction system for chronic leg ulcers based on fuzzy logic; part I - exploring the venous side. AB - Chronic leg ulcers (CLUs) are a common occurrence in the western population and are associated with a negative impact on the quality of life of patients. They also cause a substantial burden on the health budget. The pathogenesis of leg ulceration is quite heterogeneous, and chronic venous ulceration (CVU) is the most common manifestation representing the main complication of chronic venous disease (CVD). Prevention strategies and early identification of the risk represent the best form of management. Fuzzy logic is a flexible mathematical system that has proved to be a powerful tool for decision-making systems and pattern classification systems in medicine. In this study, we have elaborated a computerised prediction system for chronic leg ulcers (PredyCLU) based on fuzzy logic, which was retrospectively applied on a multicentre population of 77 patients with CVD. This evaluation system produced reliable risk score patterns and served effectively as a stratification risk tool in patients with CVD who were at the risk of developing CVUs. PMID- 26542427 TI - Pitfalls in adrenal imaging. PMID- 26542428 TI - Pitfalls in imaging of female infertility. PMID- 26542429 TI - Pitfalls in imaging for advanced ovarian cancer. PMID- 26542431 TI - Mimics of hepatic neoplasms. PMID- 26542430 TI - Common technical and anatomical pitfalls in the evaluation of multiparametric prostate magnetic resonance imaging. PMID- 26542432 TI - Pitfalls in pancreatic imaging. PMID- 26542433 TI - Pitfalls in imaging after gastrointestinal surgery. PMID- 26542434 TI - AMP-Conjugated Quantum Dots: Low Immunotoxicity Both In Vitro and In Vivo. AB - Quantum dots (QDs) are engineered nanoparticles that possess special optical and electronic properties and have shown great promise for future biomedical applications. In this work, adenosine 5'-monophosphate (AMP), a small biocompatible molecular, was conjugated to organic QDs to produce hydrophilic AMP QDs. Using macrophage J774A.1 as the cell model, AMP-QDs exhibited both prior imaging property and low toxicity, and more importantly, triggered limited innate immune responses in macrophage, indicating low immunotoxicity in vitro. Using BALB/c mice as the animal model, AMP-QDs were found to be detained in immune organs but did not evoke robust inflammation responses or obvious histopathological abnormalities, which reveals low immunotoxicity in vivo. This work suggests that AMP is an excellent surface ligand with low immunotoxicity, and potentially used in surface modification for more extensive nanoparticles. PMID- 26542435 TI - Sample injection and electrophoretic separation on a simple laminated paper based analytical device. AB - We described a strategy to perform multistep operations on a simple laminated paper-based separation device by using electrokinetic flow to manipulate the fluids. A laminated crossed-channel paper-based separation device was fabricated by cutting a filter paper sheet followed by lamination. Multiple function units including sample loading, sample injection, and electrophoretic separation were integrated on a single paper based analytical device for the first time, by applying potential at different reservoirs for sample, sample waste, buffer, and buffer waste. As a proof-of-concept demonstration, mixed sample solution containing carmine and sunset yellow were loaded in the sampling channel, and then injected into separation channel followed by electrophoretic separation, by adjusting the potentials applied at the four terminals of sampling and separation channel. The effects of buffer pH, buffer concentration, channel width, and separation time on resolution of electrophoretic separation were studied. This strategy may be used to perform multistep operations such as reagent dilution, sample injection, mixing, reaction, and separation on a single microfluidic paper based analytical device, which is very attractive for building micro total analysis systems on microfluidic paper based analytical devices. PMID- 26542436 TI - Effect of Intercurrent Operation and Cerebral Oxygenation on Developmental Trajectory in Congenital Heart Disease. AB - BACKGROUND: Children with congenital heart disease are at increased risk of abnormal neurodevelopment (ND). Demographic and perioperative physiologic factors have both been associated with developmental outcome. The acute physiologic effect of a surgical procedure, anesthesia, and hospitalization may offset any potential advantage gained from anatomic correction and circulatory palliation. The specific risk/benefit balance on ND outcome of the insult of the operation, offset by the benefit of improved anatomy and physiology, has not been addressed. We therefore sought to identify interval procedural and physiologic factors assessed at outpatient ND evaluation visits that were associated with outcome. METHODS: The study included children with congenital heart disease at high risk for impaired ND performance with at least three ND assessments using the Bayley Scales of Infant Development-III during the first 3 years of life. The number of cardiac procedures, duration of hospitalization, feeding status, height, weight, and arterial, cerebral, and somatic oxygen saturations by near-infrared spectroscopy were recorded at each visit and used as predictors of language, motor, and cognitive composite scores and slopes (change over time) in general linear models. RESULTS: Data on 178 children derived from 632 visits (median, 4 visits/child) were analyzed, with ages at first and last assessment of 7.7 and 30.2 months. Fifty-one had 1 ventricle (1V), 88 had 2 ventricles, and 39 had genetic syndrome conditions. Motor performance increased with age in all diagnostic categories. Cognitive and language performance increased with age in 1V patients but exhibited no significant change in 2-ventricle and genetic syndrome groups. At the first visit, 1V patients performed less well than 2 ventricle patients in the motor domain, but the rate of improvement was higher for 1V patients; by 24 months, there were no differences, and both groups were normal in all domains. Performance in genetic syndrome patients was below normal in all domains at the first visit and did not improve. Higher arterial saturation and narrower arterial-cerebral and arterial-somatic near-infrared spectroscopy saturation differences were associated with better or improving motor performance. Incremental cardiopulmonary bypass time, cumulative hospital length of stay, and tube feedings were risk factors in all domains. Total and incremental times for deep hypothermic circulatory arrest, extracorporeal membrane oxygenation, total open and total surgical procedures, and birth weight were not risk factors. CONCLUSIONS: Patient physiologic status assessed by cerebral and somatic near-infrared spectroscopy is associated with ND performance. Incremental surgical procedures are not associated with ND performance when adjusted for cardiopulmonary bypass time and physiologic status. Treatment strategies that target improved physiologic status may also improve ND outcome. PMID- 26542437 TI - Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database. AB - BACKGROUND: The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) has been successfully linked to the Centers for Medicare and Medicaid (CMS) Medicare database, thereby facilitating comparative effectiveness research and providing information about long-term follow-up and cost. The present study uses this link to determine contemporary completeness, penetration, and representativeness of the STS ACSD. METHODS: Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft (CABG) surgery hospitalizations discharged between 2000 and 2012, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. RESULTS: Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% in 2000 to 90% in 2012. In 2012, 973 of 1,081 CMS CABG sites (90%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% in 2000 to 94% in 2012. In 2012, 71,634 of 76,072 CMS CABG hospitalizations (94%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2012. In 2012, 69,213 of 70,932 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. CONCLUSIONS: Linkage of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data facilitates studying long-term outcomes and costs of cardiothoracic surgery. PMID- 26542438 TI - Oncologic Outcomes of Segmentectomy Versus Lobectomy for Clinical T1a N0 M0 Non Small Cell Lung Cancer. AB - BACKGROUND: We retrospectively compared the oncologic outcome after segmentectomy versus lobectomy in patients with clinical (c-) T1a N0 M0 non-small cell lung cancer (NSCLC) detected as a part-solid ground-glass nodule or purely solid nodule on thin-section computed tomography. METHODS: From 1997 to 2010, 312 patients with c-T1a N0 M0 NSCLC were determined to require a surgical approach categorized as segmentectomy or lobectomy. Preoperatively available data were collected using logistic regression analysis, and propensity matching was performed. Factors affecting local-regional recurrence were assessed by Cox proportional hazards regression analysis and Kaplan-Meier estimates. RESULTS: The 5-year and 10-year overall survival rates for the 80 patients who underwent segmentectomy were 97.5% and 83.5%, respectively, compared with 87.75% and 75.0%, respectively, for the 232 patients who underwent lobectomy (p = 0.019). Local regional recurrence as the first relapse site was found in 3 the 80 segmentectomies (3.8%) of and in 15 of the 232 lobectomies (6.5%). The difference in local-regional recurrence-free survival in patients undergoing segmentectomy compared with lobectomy was not significant (p = 0.304). In 69 propensity score matched pairs, there was no significant difference in the overall survival (p = 0.442) or local-regional recurrence-free survival (p = 0.717) between the two groups. Multivariate analysis using the Cox proportional hazards regression model identified lymphatic invasion as the only independent factor predicting local regional recurrence (relative risk, 10.764; 95% confidence interval, 2.98 to 57.68). CONCLUSIONS: Our results suggest that the oncologic outcome of segmentectomy vs lobectomy is similar in this cohort of c-T1a N0 M0 NSCLC patients. These results will be validated by large-scale, prospective, randomized trials. PMID- 26542440 TI - Abstracts of the 24th Malaysian Urological Conference MUC 2015, 19 November 2015, Malaysia. PMID- 26542439 TI - Aggressive Aortic Arch and Carotid Replacement Strategy for Type A Aortic Dissection Improves Neurologic Outcomes. AB - BACKGROUND: International registries for acute type A aortic dissection (TAAD) demonstrate stagnant operative mortality rates in excess of 20% and stroke rates of 9% to 25%, with little global emphasis on stroke reduction or carotid involvement. Cerebral malperfusion with TAAD has been linked to poorer outcome. We hypothesize that concomitant carotid dissection or complex dissection flaps in the arch play a major role in stroke development and that aggressive reconstruction of the arch and carotid arteries can improve neurologic outcomes in TAAD. METHODS: A standardized protocol focused on expedient care, neurocerebral protection, and common carotid and total arch reconstruction was developed for 264 consecutive TAADs. Arch and complete carotid replacement was based on arch dissection anatomy, carotid involvement, or an intraarch tear. Neurocerebral monitoring with continuous electroencephalogram/somatosensory evoked potentials was used in all cases. RESULTS: The postoperative stroke and hospital mortality rates were 3.4% and 9.1%, and stroke rates by extent of arch replacement were 4%, 3%, and 0% for hemiarch, total arch, and total arch with complete carotid replacement, respectively. An intraoperative change in the electroencephalogram/somatosensory evoked potentials was strongly predictive of stroke and had a negative predictive value of 98.2%. CONCLUSIONS: An algorithmic approach to TAAD including (1) rapid transport-to-incision-to-cardiopulmonary bypass established centrally, (2) neurocerebral monitoring, (3) liberal use of total arch replacement for clearly defined indications (and hemiarch for all others), and (4) common carotid arterial replacement for concomitant carotid dissections significantly improves outcomes. PMID- 26542442 TI - Can they do it? Comparing the views of pharmacists and technicians to the introduction of an advanced technician role. AB - OBJECTIVES: This study aimed to investigate the opinions of pharmacists and technicians regarding the ability of New Zealand technicians to take on an advanced checking technician role. METHODS: A survey was developed to investigate the opinions regarding the introduction of this new role. The questions covered are: perceived ability to take on the role, training requirements and competence. Surveys were sent to pharmacists whose contact details are available for research purposes (n = 2095) and to all pharmacies in New Zealand (both community and hospital) for the attention of technicians (n = 858). The results were analysed using IBM SPSS and thematic analysis of comments was conducted. KEY FINDINGS: A total of 1221 surveys were returned (pharmacists = 736 and technicians = 485). The majority of the technicians (83%) believed that 'some' technicians could work in a CT role, compared with 73% of the pharmacists. Over two-thirds (69%) of the technicians felt comfortable checking a prescription at their current level of training compared with 53% of pharmacists. Both groups' comfort increased with further specific training for the technicians. CONCLUSIONS: The majority of both of these groups supported the change in roles. Pharmacists were less confident that technicians could take on this role now, but were more comfortable after extra training had been completed. The technicians, however, were confident they could take on this role now but would take on extra training if needed. PMID- 26542445 TI - Introduction to selected papers from GIW/InCoB 2015. PMID- 26542444 TI - Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis. AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12.2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1.9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3.0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted. PMID- 26542441 TI - Enhanced Photosynthesis and Growth in atquac1 Knockout Mutants Are Due to Altered Organic Acid Accumulation and an Increase in Both Stomatal and Mesophyll Conductance. AB - Stomata control the exchange of CO2 and water vapor in land plants. Thus, whereas a constant supply of CO2 is required to maintain adequate rates of photosynthesis, the accompanying water losses must be tightly regulated to prevent dehydration and undesired metabolic changes. Accordingly, the uptake or release of ions and metabolites from guard cells is necessary to achieve normal stomatal function. The AtQUAC1, an R-type anion channel responsible for the release of malate from guard cells, is essential for efficient stomatal closure. Here, we demonstrate that mutant plants lacking AtQUAC1 accumulated higher levels of malate and fumarate. These mutant plants not only display slower stomatal closure in response to increased CO2 concentration and dark but are also characterized by improved mesophyll conductance. These responses were accompanied by increases in both photosynthesis and respiration rates, without affecting the activity of photosynthetic and respiratory enzymes and the expression of other transporter genes in guard cells, which ultimately led to improved growth. Collectively, our results highlight that the transport of organic acids plays a key role in plant cell metabolism and demonstrate that AtQUAC1 reduce diffusive limitations to photosynthesis, which, at least partially, explain the observed increments in growth under well-watered conditions. PMID- 26542446 TI - EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles. AB - Determining the entire complement of enzymes and their enzymatic functions is a fundamental step for reconstructing the metabolic network of cells. High quality enzyme annotation helps in enhancing metabolic networks reconstructed from the genome, especially by reducing gaps and increasing the enzyme coverage. Currently, structure-based and network-based approaches can only cover a limited number of enzyme families, and the accuracy of homology-based approaches can be further improved. Bottom-up homology-based approach improves the coverage by rebuilding Hidden Markov Model (HMM) profiles for all known enzymes. However, its clustering procedure relies firmly on BLAST similarity score, ignoring protein domains/patterns, and is sensitive to changes in cut-off thresholds. Here, we use functional domain architecture to score the association between domain families and enzyme families (Domain-Enzyme Association Scoring, DEAS). The DEAS score is used to calculate the similarity between proteins, which is then used in clustering procedure, instead of using sequence similarity score. We improve the enzyme annotation protocol using a stringent classification procedure, and by choosing optimal threshold settings and checking for active sites. Our analysis shows that our stringent protocol EnzDP can cover up to 90% of enzyme families available in Swiss-Prot. It achieves a high accuracy of 94.5% based on five-fold cross-validation. EnzDP outperforms existing methods across several testing scenarios. Thus, EnzDP serves as a reliable automated tool for enzyme annotation and metabolic network reconstruction. Available at: www.comp.nus.edu.sg/~nguyennn/EnzDP . PMID- 26542447 TI - Electrostatics of DNA nucleotide-carbon nanotube hybrids evaluated from QM:MM simulations. AB - Biomolecule-functionalized carbon nanotubes (CNTs) have been studied vastly in recent years due to their potential applications for instance in cancer detection, purification and separation of CNTs, and nanoelectronics. Studying the electrostatic potential generated by a biomolecule-CNT hybrid is important in predicting its interactions with the surrounding environment such as charged particles and surfaces. In this paper, we performed atomistic simulations using a QM:MM approach to evaluate the electrostatic potential and charge transfer for a hybrid structure formed by a DNA nucleotide and a CNT in solution. Four types of DNA nucleotides and two CNTs with chiralities of (4,4) and (7,0) were considered. The types of nucleotides and CNTs were both found to play important roles in the electrostatic potential and charge transfer of the hybrid. At the same distance from the CNT axis, the electrostatic potential for the nucleotide-(4,4) CNT hybrids was found to be stronger compared with that for the nucleotide-(7,0) CNT hybrids. Higher electric charge was also shown to be transferred from the DNA nucleotides to the (7,0) CNT compared with the (4,4) CNT. These results correlate with the previous finding that the nucleotides bound more tightly to the (7,0) CNT compared with the (4,4) CNT. PMID- 26542448 TI - Sporadic MM2-thalamic + cortical Creutzfeldt-Jakob disease: Utility of diffusion tensor imaging in the detection of cortical involvement in vivo. AB - In sporadic Creutzfeldt-Jakob disease (sCJD), high signal intensity in fluid attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences in striatum and/or cortical regions of the brain are present in about 83% of cases, reflecting tissue damage, such as spongiform change and abnormal prion protein deposits. Novel diffusion sequences of MRI might improve the detection of CJD characteristic changes in the subset of patients in whom these alterations are absent or less evident. We report a neuropathologically confirmed case of the rare MM2 T + C subtype of sCJD, with mixed clinical and neuropathological features of MM2 thalamic and MM2 cortical subtypes, in whom the use of diffusion tensor imaging helped to identify cortical hyperintensities that could be easily overlooked with conventional DWI. PMID- 26542449 TI - Two-phase and three-phase liquid-phase microextraction of hydrochlorothiazide and triamterene in urine samples. AB - This paper reports the applicability of two-phase and three-phase hollow fiber based liquid-phase microextraction (HF-LPME) for the extraction of hydrochlorothiazide (HYD) and triamterene (TRM) from human urine. The HYD in two phase HF-LPME is extracted from 24 mL of the aqueous sample into an organic phase with microliter volume located inside the pores and lumen of a polypropylene hollow fiber as acceptor phase, but the TRM in three-phase HF-LPME is extracted from aqueous donor phase to organic phase and then back-extracted to the aqueous acceptor phase, which can be directly injected into HPLC for analysis. Under optimized conditions preconcentration factors of HYD and TRM were obtained as 128 and 239, respectively. The calibration curves were linear (R(2) >= 0.995) in the concentration range of 1.0-100 ug/L for HYD and 2.0-100 ug/L for TRM. The limits of detection for HYD and TRM were 0.5 ug/L. The intra-day and inter-day RSD based on four replicates were obtained as <=5.8 and <=9.3%, respectively. The methods were successfully applied for determining the concentration of the drugs in urine samples. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26542450 TI - Pharmacokinetics of single-dose oral ponazuril in weanling goats. AB - Ponazuril (toltrazuril sulfone) is a triazine antiprotozoal agent that targets apicomplexan organisms. Ponazuril may have clinical application in the treatment of clinical coccidiosis due to Eimeria species in goats, along with other protozoal infections. To evaluate the absorption, distribution and elimination characteristics of ponazuril in goats, a sensitive, validated high-pressure liquid chromatography and mass spectroscopy method for ponazuril in caprine plasma was developed. After a single oral dose of ponazuril at 10 mg/kg, plasma samples from seven weanling goats were collected and assayed. Plasma concentrations of ponazuril in the goats peaked at 36 +/- 13 h post drug administration at a concentration of 9 +/- 2 MUg/mL. Concentrations declined to an average of 4.2 +/- 0.8 MUg/mL after 168 h with an average elimination half life of 129 +/- 72 h post drug administration. This study shows that ponazuril is relatively well absorbed after a single oral dose in goats. Efficacy trials are underway to determine clinical efficacy of ponazuril in the treatment of clinical coccidiosis in goats at 10 mg/kg dosage. PMID- 26542454 TI - Forced degradation studies of biopharmaceuticals: Selection of stress conditions. AB - Stability studies under stress conditions or forced degradation studies play an important role in different phases of development and production of biopharmaceuticals and biological products. These studies are mostly applicable to selection of suitable candidates and formulation developments, comparability studies, elucidation of possible degradation pathways and identification of degradation products, as well as, development of stability indicating methods. Despite the integral part of these studies in biopharmaceutical industry, there is no well-established protocol for the selection of stress conditions, timing of stress testing and required extent of degradation. Therefore, due to the present gap in the stability studies guidelines, it is the responsibility of researchers working in academia and biopharmaceutical industry to set up forced degradation experiments that could fulfill all the expectations from the stability studies of biopharmaceuticals under stress conditions. Concerning the importance of the function of desired stress conditions in forced degradation studies, the present review aims to provide a practical summary of the applicable stress conditions in forced degradation studies of biopharmaceuticals according to the papers published in a time period of 1992-2015 giving detailed information about the experimental conditions utilized to induce required stresses. PMID- 26542452 TI - Nuclear PKM2 contributes to gefitinib resistance via upregulation of STAT3 activation in colorectal cancer. AB - Gefitinib (Iressa, ZD-1839), a small molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) pathway, is currently under investigation in clinical trials for the treatment of colorectal cancer (CRC). However, as known, some patients develop resistance to TKIs, and the mechanisms mediating intrinsic resistance to EGFR-TKIs in CRC have not been fully characterized. Resistance to EGFR inhibitors reportedly involves activation of signal transducer and activator of transcription 3 (STAT3) in glioma and lung cancer. Here, we demonstrated that the nuclear pyruvate kinase isoform M2 (PKM2) levels were positively correlated with gefitinib resistance in CRC cells. The overexpression of nuclear PKM2 in HT29 cells decreased the effect of gefitinib therapy, whereas PKM2 knockdown increased gefitinib efficacy. Furthermore, the activation of STAT3 by nuclear PKM2 was associated with gefitinib resistance. Inhibition of STAT3 by Stattic, a STAT3-specific inhibitor, or STAT3-specific siRNA sensitized resistant cells to gefitinib. These results suggest that nuclear PKM2 modulates the sensitivity of CRC cells to gefitinib and indicate that small molecule pharmacological disruption of nuclear PKM2 association with STAT3 is a potential avenue for overcoming EGFR-TKI resistance in CRC patients. PMID- 26542455 TI - Directed Self-Assembly of Block Copolymer Micelles onto Topographically Patterned Surface. AB - We report a facile method to control directed self-assembly (DSA) of spherical micelles of block copolymers (BCPs) by topographically patterned surface. A cylinder-forming polystyrene-block-poly(2-vinylpyridine) copolymer [Mn,PS = 175 kg/mol, Mn,P2VP = 70 kg/mol, and polydipersity index (PDI) = 1.08] was phase separated on a thin film of poly(vinyl alcohol) (PVA) by solvent annealing. By additional treatment with ethanol as a preferential solvent for P2VP block, the surface of BCP thin film was reconstructed to produce nanopores. Nanoporous structures in BCP thin films were transferred to the underlying hydrophilic PVA film by reactive ion etching (RIE). Then spherical BCP micelles were quickly self assembled within the nanopores in the PVA layer due to topographical contrast and surface energy difference during spin-coating. Consequently, the site-selective array of BCP micelles was utilized as templates to achieve heterogeneous organization of nanoparticles and organic fluorescent dyes over a large area. In addition, it was observed that those heterogeneous assemblies showed a remarkable decrease in fluorescence intensity of organic dyes. PMID- 26542456 TI - Multiple exaggerated weapon morphs: a novel form of male polymorphism in harvestmen. AB - Alternative reproductive tactics in animals are commonly associated with distinct male phenotypes resulting in polymorphism of sexually selected weapons such as horns and spines. Typically, morphs are divided between small (unarmed) and large (armed) males according to one or more developmental thresholds in association with body size. Here, we describe remarkable weapon trimorphism within a single species, where two exaggerated weapon morphs and a third morph with reduced weaponry are present. Male Pantopsalis cheliferoides harvestmen display exaggerated chelicerae (jaws) which are highly variable in length among individuals. Across the same body size spectrum, however, some males belong to a distinct second exaggerated morph which possesses short, broad chelicerae. Multiple weapon morphs in a single species is a previously unknown phenomenon and our findings have significant implications for understanding weapon diversity and maintenance of polymorphism. Specifically, this species will be a valuable model for testing how weapons diverge by being able to test directly for the circumstances under which a certain weapon type is favoured and how weapon shape relates to performance. PMID- 26542451 TI - Targeting voltage-gated calcium channels in neurological and psychiatric diseases. AB - Voltage-gated calcium channels are important regulators of brain, heart and muscle functions, and their dysfunction can give rise to pathophysiological conditions ranging from cardiovascular disorders to neurological and psychiatric conditions such as epilepsy, pain and autism. In the nervous system, calcium channel blockers have been used successfully to treat absence seizures, and are emerging as potential therapeutic avenues for pathologies such as pain, Parkinson disease, addiction and anxiety. This Review provides an overview of calcium channels as drug targets for nervous system disorders, and discusses potential challenges and opportunities for the development of new clinically effective calcium channel inhibitors. PMID- 26542457 TI - Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats. AB - Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1 34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia. PMID- 26542458 TI - Review of Environmental Assessment Case Studies Blending Elements of Risk Assessment and Life Cycle Assessment. AB - Risk assessment (RA) and life cycle assessment (LCA) are two analytical tools used to support decision making in environmental management. This study reviewed 30 environmental assessment case studies that claimed an integration, combination, hybridization, or complementary use of RA and LCA. The focus of the analysis was on how the respective case studies evaluated emissions of chemical pollutants and pathogens. The analysis revealed three clusters of similar case studies. Yet, there seemed to be little consensus as to what should be referred to as RA and LCA, and when to speak of combination, integration, hybridization, or complementary use of RA and LCA. This paper provides clear recommendations toward a more stringent and consistent use of terminology. Blending elements of RA and LCA offers multifaceted opportunities to adapt a given environmental assessment case study to a specific decision making context, but also requires awareness of several implications and potential pitfalls, of which six are discussed in this paper. To facilitate a better understanding and more transparent communication of the nature of a given case study, this paper proposes a "design space" (i.e., identification framework) for environmental assessment case studies blending elements of RA and LCA. Thinking in terms of a common design space, we postulate, can increase clarity and transparency when communicating the design and results of a given assessment together with its potential strengths and weaknesses. PMID- 26542460 TI - Percutaneous cholecystostomy to treat acute cholecystitis in patients with high risk for surgery. AB - OBJECTIVE: To evaluate the results of percutaneous cholecystostomy for urgent treatment of acute cholecystitis, with the aim of identifying factors that predict survival. To analyze the recurrence of cholecystitis after catheter withdrawal in patients considered unsuitable candidates for delayed surgery, with the aim of identifying factors that predict recurrence. MATERIAL AND METHODS: We reviewed 40 patients who underwent percutaneous cholecystostomy in a two-year period. We analyzed survival during hospitalization in relation with fever, abdominal pain, leukocytosis, and C-reactive protein before and after the procedure. We analyzed the recurrence of cholecystitis after catheter withdrawal in patients considered unsuitable candidates for delayed surgery, as well as the influence of obstruction seen on cholangiography, age, sex, and comorbidities on the recurrence rate. RESULTS: During the hospital stay, 4 (10%) patients died of septic shock. Cholecystostomy improved fever, leukocytosis, and abdominal pain within five days of the procedure, but these improvements did not have a statistically significant effect on survival and were not therefore considered useful prognostic factors. Among the 15 patients considered unsuitable candidates for delayed surgery, 6 (40%) had recurrences of cholecystitis during a mean follow-up period of 6.7 months after catheter withdrawal. We found no association between recurrence and any of the parameters analyzed. CONCLUSIONS: Outcomes in our series of patients with high risk for surgery who underwent cholecystostomy for urgent treatment of acute cholecystitis were similar to those reported in other series. Withdrawing the catheter in patients considered unsuitable candidates for delayed surgery is not recommended due to the high risk of recurrence of cholecystitis in comparison with other series. PMID- 26542461 TI - Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila. AB - Caspases are the executioners of apoptosis. Although much is known about their physiological roles and structures, detailed analyses of missense mutations of caspases are lacking. As mutations within caspases are identified in various human diseases, the study of caspase mutants will help to elucidate how caspases interact with other components of the apoptosis pathway and how they may contribute to disease. DrICE is the major effector caspase in Drosophila required for developmental and stress-induced cell death. Here, we report the isolation and characterization of six de novo drICE mutants, all of which carry point mutations affecting amino acids conserved among caspases in various species. These six mutants behave as recessive loss-of-function mutants in a homozygous condition. Surprisingly, however, two of the newly isolated drICE alleles are gain-of-function mutants in a heterozygous condition, although they are loss-of function mutants homozygously. Interestingly, they only behave as gain-of function mutants in the presence of an apoptotic signal. These two alleles carry missense mutations affecting conserved amino acids in close proximity to the catalytic cysteine residue. This is the first time that viable gain-of-function alleles of caspases are described in any intact organism and provides a significant exception to the expectation that mutations of conserved amino acids always abolish the pro-apoptotic activity of caspases. We discuss models about how these mutations cause the gain-of-function character of these alleles. PMID- 26542463 TI - Investigation of reference gene expression during human herpesvirus 6B infection indicates peptidylprolyl isomerase A as a stable reference gene and TATA box binding protein as a gene up-regulated by this virus. AB - When using relative gene expression for quantification of RNA it is crucial that the reference genes used for normalization do not change with the experimental condition. We aimed at investigating the expressional stability of commonly used reference genes during Human herpesvirus 6B (HHV-6B) infection. Expression of eight commonly used reference genes were investigated with quantitative PCR in a T-cell line infected with HHV-6B. The stability of genes was investigated using the 2(-DeltaDeltaCT) method and the algorithms BestKeeper, GeNorm and NormFinder. Our results indicate that peptidylprolyl isomerase A (PPIA) is the most stably expressed gene while TATA box binding protein (TBP) is the least stably expressed gene during HHV-6B infection. In a confirmatory experiment, TBP was demonstrated to be dose and time dependently upregulated by HHV-6B. The stability of PPIA is in line with other studies investigating different herpesvirus infections whereas the finding that HHV-6B significantly upregulates TBP is novel and most likely specific to HHV-6B. PMID- 26542462 TI - p38 MAPK mediates glial P2X7R-neuronal P2Y1R inhibitory control of P2X3R expression in dorsal root ganglion neurons. AB - BACKGROUND: We have previously shown that endogenously active purinergic P2X7 receptors (P2X7Rs) in satellite glial cells of dorsal root ganglia (DRGs) stimulate ATP release. The ATP activates P2Y1Rs located in the enwrapped neuronal somata, resulting in down-regulation of P2X3Rs. This P2X7R-P2Y1-P2X3R inhibitory control significantly reduces P2X3R-mediated nociceptive responses. The underlying mechanism by which the activation of P2Y1Rs inhibits the expression of P2X3Rs remains unexplored. RESULTS: Examining the effect of the activation of p38 mitogen-activated protein kinase on the expression of P2X3Rs in DRGs, we found that the p38 activator, anisomycin (Anis), reduced the expression of P2X3Rs. Blocking the activity of SGCs by the glial Krebs cycle inhibitor, fluorocitrate, did not change the effect of Anis. These results suggest that neuronal p38 plays a major role in the inhibition of P2X3R expression. Western blotting analyses showed that inhibiting P2Y1Rs by MRS2179 (MRS) or blocking P2X7Rs by either oxATP or A740003 reduced pp38 and increased P2X3R expression in DRGs. These results are further supported by the immunohistochemical study showing that P2X7R and P2Y1R antagonists reduce the percentage of pp38-positive neurons. These observations suggest that activation of P2X7Rs and P2Y1Rs promotes p38 activity to exert inhibitory control on P2X3R expression. Since activation of p38 by Anis in the presence of either A740003 or MRS could overcome the block of P2X7R-P2Y1R inhibitory control, p38 in DRG neurons is downstream of P2Y1Rs. In addition, inhibition of p38 by SB202190 was found to prevent the P2X7R and P2Y1R block of P2X3R expression and increase P2X3R-mediated nociceptive flinch behaviors. CONCLUSIONS: p38 in DRG neurons downstream of P2Y1R is necessary and sufficient for the P2X7R-P2Y1R inhibitory control of P2X3R expression. PMID- 26542464 TI - Should we still use motor vehicle intrusion as a sole triage criterion for the use of trauma center resources? AB - BACKGROUND: Motor vehicle intrusion (MVI) is one of the field triage criteria recommended by the American College of Surgeons Committee of Trauma (ACS-COT) and Centers for Disease Control and Prevention (CDC). However, the evidence supporting its validity is scarce. The purpose of this study was to evaluate the validity of this criterion and assess its impact on overtriage or undertriage. PATIENTS AND METHODS: This was a retrospective study based on the Los Angeles County Trauma and Emergency Medicine Information System (TEMIS) Trauma database. Included in the analysis were patients with MVI as the sole criterion for trauma center triage. Physiological characteristics, severity of injury, and outcomes of the MVI patients were compared between different age groups. Further, a logistic regression model was used to identify factors significantly associated with the need for trauma center resources. RESULTS: During the period 2002-2012, a total of 10,554 trauma patients involved in motor vehicle crashes had documentation of MVI. A subgroup of 3998 patients (37.9%) did not meet any other criteria that require immediate transportation to a designated trauma center. Only 0.7% of these patients had hypotension and 0.1% had deterioration of the Glasgow Coma Scale on admission to the emergency room. Overall, 18.8% of patients required trauma center resources defined as intubation in the emergency room, certain surgical procedures, in-hospital death, or intensive care unit admission. Age >=65 years, male gender, prehospital heart rate >100/min, and systolic blood pressure <110 mmHg were significantly associated with the need for trauma center resources. CONCLUSIONS: The MVI itself did not appear to be a strong indicator for the use of trauma center resources and is associated with excessive overtriage. However, age >65 years, systolic blood pressure <110 mmHg, and heart rate >100/min were significant predictors for the need of trauma center resources. The MVI criterion should be refined for better utilization of trauma center resources. PMID- 26542465 TI - Neonatal focal seizures and hypomagnesemia: A case report. AB - BACKGROUND: In seizures caused by electrolytes disorders, a prompt diagnosis allows an appropriate treatment and reduces the risk of neurological complications. Hypomagnesemia is a recognized cause of generalized seizures, while it has been anecdotally reported in focal forms. CASE PRESENTATION: We describe a newborn with recurrent focal seizures due to transient hypomagnesemia. CONCLUSION: Physicians should consider the possible occurrence of such disorder also in cases of focal seizures. PMID- 26542466 TI - TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability. AB - BACKGROUND: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49). RESULTS: We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events. CONCLUSION: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin. PMID- 26542467 TI - Measuring the positive psychological well-being of people with rheumatoid arthritis: a cross-sectional validation of the subjective vitality scale. AB - INTRODUCTION: People with rheumatoid arthritis (RA) frequently suffer from compromised physical and psychological health, however, little is known about positive indicators of health, due to a lack of validated outcome measures. This study aims to validate a clinically relevant outcome measure of positive psychological well-being for people with RA. The first study examined the reliability and factorial validity of the Subjective Vitality Scale (SVS), whilst study 2 tested the instruments convergent validity. METHODS: In study 1, National Rheumatoid Arthritis Society members (N = 333; M age = 59.82 years SD = 11.00) completed a postal questionnaire. For study 2, participants (N = 106; M age = 56 years, SD = 12 years) were those recruited to a randomized control trial comparing two physical activity interventions who completed a range of health related questionnaires. RESULTS: The SVS had a high level of internal consistency (alpha = .93, Rho = .92). Confirmatory factor analysis supported the uni dimensional factor structure of the questionnaire among RA patients [chi = 1327 (10), CFI = 1.0, SRMSR = .01 and RMSEA = .00 (.00 - .08)]. Support for the scales convergent validity was revealed by significant (p < .05) relationships, in expected directions, with health related quality of life (r = .59), physical function (r = .58), feelings of fatigue (r = -.70), anxiety (r = -.57) and depression (r = -.73). CONCLUSIONS: Results from two studies have provided support for the internal consistency, factorial structure and convergent validity of the Subjective Vitality Scale. Researchers and healthcare providers may employ this clinically relevant, freely available and brief assessment with the confidence that it is a valid and reliable measure of positive psychological well being for RA patients. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN04121489 . Registered 5 September 2012. PMID- 26542468 TI - Developmental assessment of VLBW infants at 18 months of age: A comparison study between KSPD and Bayley III. AB - AIM: To assess the developmental characteristics of very low-birth-weight (VLBW) infants using the Kyoto Scale of Psychological Development (KSPD) and to compare with those using the Bayley Scales, third edition (Bayley III). METHODS: KSPD and Bayley III were performed on 124 Japanese VLBW infants at 18months of corrected age at a 2-week interval by trained psychologists. The relationships between KSPD and Bayley III in corresponding pairs: Cognitive-Adaptive (C-A) developmental quotient (DQ) and cognitive composite (Cog) scores, Language-Social (L-S) DQ and language composite (Lang) scores, and Postural-Motor (P-M) DQ and motor composite (Mot) scores were analyzed. RESULTS: The means [SD] of C-A DQ, L-S DQ, P-M DQ, and overall DQ of KSPD were 94 [15], 90 [17], 89 [15], and 93 [14], respectively. The means [SD] of the Cog, Lang, and Mot scores of Bayley III were 96 [13], 84 [12], and 91 [12], respectively. The DQ of KSPD strongly correlated with the corresponding composite score of Bayley III; Spearman rank correlations between the Cog score and C-A DQ, the Lang score and L-S DQ, and the Mot score and P-M DQ were 0.65, 0.71 and 0.55, respectively. The selected cut-off of the Cog score of <85 accurately identified development delay, defined by KSPD, with sensitivity of 100% and specificity of 85%. CONCLUSION: Although absolute value of the Bayley III score may not represent the degree of impairment, the developmental characteristics on KSPD well correlated with those on Bayley III. The developmental outcomes of Japanese VLBW infants were verified by the two tests. PMID- 26542469 TI - Cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-D-aspartate receptor encephalitis: A case series. AB - BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. METHOD: We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5 years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. RESULTS: Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. CONCLUSION: Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population. PMID- 26542470 TI - Identifying rapidly parasiticidal anti-malarial drugs using a simple and reliable in vitro parasite viability fast assay. AB - BACKGROUND: The emergence of Plasmodium falciparum resistance to artemisinins threatens to undermine the effectiveness of artemisinin-based combination anti malarial therapy. Developing suitable drugs to replace artemisinins requires the identification of new compounds that display rapid parasite killing kinetics. However, no current methods fully meet the requirements to screen large compound libraries for candidates with such properties. This study describes the development and validation of an in vitro parasite viability fast assay for identifying rapidly parasiticidal anti-malarial drugs. METHODS: Parasite killing kinetics were determined by first culturing unlabelled erythrocytes with P. falciparum in the presence of anti-malarial drugs for 24 or 48 h. After removing the drug, samples were added to erythrocytes pre-labelled with intracellular dye to allow their subsequent identification. The ability of viable parasites to re establish infection in labelled erythrocytes could then be detected by two-colour flow cytometry after tagging of parasite DNA. Thus, double-stained erythrocytes (with the pre-labelled intracellular dye and the parasite DNA dye) result only after establishment of new infections by surviving parasites. The capacity of the test anti-malarial drugs to eliminate viable parasites within 24 or 48 h could, therefore, be determined. RESULTS: The parasite viability fast assay could be completed within 48 h following drug treatment and distinguished between rapidly parasiticidal anti-malarial drugs versus those acting more slowly. The assay was validated against ten standard anti-malarial agents with known properties and results correlated well with established methods. An abbreviated assay, suitable for adaption to medium-high throughput screening, was validated and applied against a set of 20 compounds retrieved from the publically available Medicines for Malaria Venture 'Malaria Box'. CONCLUSION: The quantification of new infections to determine parasite viability offers important advantages over existing methods, and is amenable to medium-high throughput screening. In particular, the parasite viability fast assay allows discrimination of rapidly parasiticidal anti-malarial candidates. PMID- 26542472 TI - How the cation 1-butyl-3-methylimidazolium impacts the interaction between the entrapped water and the reverse micelle interface created with an ionic liquid like surfactant. AB - The behavior of the interfacial water entrapped in reverse micelles (RMs) formed by the ionic liquid-like surfactant 1-butyl-3-methylimidazolium 1,4-bis-2 ethylhexylsulfosuccinate (bmim-AOT) dissolved in benzene (or chlorobenzene) was investigated using noninvasive techniques such as dynamic light scattering (DLS), static light scattering (SLS), FT-IR and (1)H NMR. The DLS and SLS results reveal the formation of discrete spherical and non-interacting water droplets stabilized by the bmim-AOT surfactant. Moreover, since the droplet size increases as the W0 (W0 = [water]/[surfactant]) value increases, water interacts with the RM interface. From FT-IR and (1)H NMR data, a weaker water-surfactant interaction in bmim-AOT RMs in comparison with the RMs created by sodium 1,4-bis-2 ethylhexylsulfosuccinate (Na-AOT) is detected. Consequently, there are less water molecules interacting with the interface in bmim-AOT RMs, and their hydrogen bond network is not completely disrupted as they are in Na-AOT RMs. The results show how the nature of the new cation impacts the interaction between the entrapped water and the RM interface, modifying the interfacial water structure in comparison with the results known for Na-AOT. PMID- 26542471 TI - Health evaluation and referral assistant: a randomized controlled trial to improve smoking cessation among emergency department patients. AB - BACKGROUND: Computer technologies hold promise for implementing tobacco screening, brief intervention, and referral to treatment (SBIRT). This study aims to evaluate a computerized tobacco SBIRT system called the Health Evaluation and Referral Assistant (HERA). METHODS: Smokers (n = 421) presenting to an emergency department were randomly assigned to the HERA or a minimal-treatment Control and were followed for 3 months. Analyses compared smoking cessation treatment provider contact, treatment initiation, treatment completion, and smoking behavior across condition using univariable comparisons, generalized estimating equations (GEE), and post hoc Chi square analyses. RESULTS: HERA participants were more likely to initiate contact with a treatment provider but did not differ on treatment initiation, quit attempts, or sustained abstinence. Subanalyses revealed HERA participants who accepted a faxed referral were more likely to initiate treatment but were not more likely to stop smoking. CONCLUSIONS: The HERA promoted initial contact with a smoking cessation provider and the faxed referral further promoted treatment initiation, but it did not lead to improved abstinence. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01153373. PMID- 26542474 TI - Low-dose CT statistical iterative reconstruction via modified MRF regularization. AB - It is desirable to reduce the excessive radiation exposure to patients in repeated medical CT applications. One of the most effective ways is to reduce the X-ray tube current (mAs) or tube voltage (kVp). However, it is difficult to achieve accurate reconstruction from the noisy measurements. Compared with the conventional filtered back-projection (FBP) algorithm leading to the excessive noise in the reconstructed images, the approaches using statistical iterative reconstruction (SIR) with low mAs show greater image quality. To eliminate the undesired artifacts and improve reconstruction quality, we proposed, in this work, an improved SIR algorithm for low-dose CT reconstruction, constrained by a modified Markov random field (MRF) regularization. Specifically, the edge preserving total generalized variation (TGV), which is a generalization of total variation (TV) and can measure image characteristics up to a certain degree of differentiation, was introduced to modify the MRF regularization. In addition, a modified alternating iterative algorithm was utilized to optimize the cost function. Experimental results demonstrated that images reconstructed by the proposed method could not only generate high accuracy and resolution properties, but also ensure a higher peak signal-to-noise ratio (PSNR) in comparison with those using existing methods. PMID- 26542473 TI - Glucose and insulin modulate sickness responses in male Siberian hamsters. AB - Mounting a sickness response is an energetically expensive task and requires precise balancing of energy allocation to ensure pathogen clearance while avoiding compromising energy reserves. Sickness intensity has previously been shown to be modulated by food restriction, body mass, and hormonal signals of energy. In the current study, we tested the hypothesis that sickness intensity is modulated by glucose availability and an endocrine signal of glucose availability, insulin. We utilized male Siberian hamsters (Phodopus sungorus) and predicted that pharmacological induction of glucoprivation with 2-deoxy-d-glucose (2-DG), a non-metabolizable glucose analog that disrupts glycolysis, would attenuate energetically expensive sickness symptoms. Alternatively, we predicted that treatment of animals with insulin would enhance energetically expensive sickness symptoms, as insulin would act as a signal of increased glucose availability. Upon experimental treatment with lipopolysaccharide (LPS), we found that glucose deprivation resulted in increased sickness-induced hypothermia as compared to control- and insulin-treated animals; however, it did not have any effects on sickness-induced anorexia or body mass loss. Insulin treatment resulted in an unexpectedly exaggerated sickness response in animals of lesser body masses; however, in animals of greater body masses, insulin actually attenuated sickness-induced body mass loss and had no effects on hypothermia or anorexia. The effects of insulin on sickness severity may be modulated by sensitivity to sickness-induced hypoglycemia. Collectively, these results demonstrate that both glucose availability and signals of glucose availability can modulate the intensity of energetically expensive sickness symptoms, but their effects differ among different sickness symptoms and are sensitive to energetic context. PMID- 26542475 TI - Argentine tango in Parkinson disease--a systematic review and meta-analysis. AB - BACKGROUND: Parkinson's Disease (PD) is a neurodegenerative disease with increasing motor and non-motor symptoms in advanced stages. In addition to conventional exercise therapy and drug treatment, Argentine Tango (AT) is discussed as an appropriate intervention for patients to improve physical functioning and health-related quality of life. This review aimed to summarize the current research results on the effectiveness of AT for individuals with PD. METHODS: The global literature search with the search terms "(Parkinson OR Parkinson's disease) AND tango" was conducted in PubMED, AMED, CAMbase, and Google Scholar for publications in English and German. There were no limitations on the study design, year of publication, stage of disease, considered outcome or the age of participants. RESULTS: Thirteen studies met the inclusion criteria. These included 9 randomized-controlled trials, one non-randomized trial, two case studies and one uncontrolled pre-post study. Our meta-analysis revealed significant overall effects in favor of tango for motor severity measured with the Unified Parkinson's Disease Rating Scale 3 (ES = -0.62, 95 % CI [-.1.04, 0.21]), balance as measured with the Mini-BESTest (ES = 0.96 [0.60, 1.31]) or Berg Balance Scale (ES = 0.45 [0.01, 0.90]), and gait with the Timed Up and Go Test (ES = -.46 [-0.72, -0.20]). However, gait as measured with a 6-Minute Walk Test did not demonstrate statistical significance (ES = 0.36 [-0.06, 0.77]). For freezing of gait, no significant effects were observed in favor of AT (ES = 0.16 [-.62, 0.31]). Further, our systematic review revealed a tendency for positive effects on fatigue, activity participation and Parkinson-associated quality of life. A limitation of the studies is the small number of participants in each study (maximum 75). Moreover, most studies are from the same research groups, and only a few are from other researchers. CONCLUSIONS: Future studies should enroll more individuals and should also focus on long-term effects. In addition, future research should address more closely the effects of AT on personal relationships, the individual social network as well as on aspects of quality of life. PMID- 26542476 TI - Influence of low ambient temperature on epitympanic temperature measurement: a prospective randomized clinical study. AB - BACKGROUND: Epitympanic temperature (Tty) measured with thermistor probes correlates with core body temperature (Tcore), but the reliability of measurements at low ambient temperature is unknown. The aim of this study was to determine if commercially-available thermistor-based Tty reflects Tcore in low ambient temperature and if Tty is influenced by insulation of the ear. METHODS: Thirty-one participants (two females) were exposed to room (23.2 +/- 0.4 degrees C) and low (-18.7 +/- 1.0 degrees C) ambient temperature for 10 min using a randomized cross-over design. Tty was measured using an epitympanic probe (M1024233, GE Healthcare Finland Oy) and oesophageal temperature (Tes) with an oesophageal probe (M1024229, GE Healthcare Finland Oy) inserted into the lower third of the oesophagus. Ten participants wore ear protectors (Arton 2200, Emil Lux GmbH & Co. KG, Wermelskirchen, Switzerland) to insulate the ear from ambient air. RESULTS: During exposure to room temperature, mean Tty increased from 33.4 +/- 1.5 to 34.2 +/- 0.8 degrees C without insulation of the ear and from 35.0 +/ 0.8 to 35.5 +/- 0.7 degrees C with insulation. During exposure to low ambient temperature, mean Tty decreased from 32.4 +/- 1.6 to 28.5 +/- 2.0 degrees C without insulation and from 35.6 +/- 0.6 to 35.2 +/- 0.9 degrees C with insulation. The difference between Tty and Tes at low ambient temperature was reduced by 82% (from 7.2 to 1.3 degrees C) with insulation of the ear. CONCLUSIONS: Epitympanic temperature measurements are influenced by ambient temperature and deviate from Tes at room and low ambient temperature. Insulating the ear with ear protectors markedly reduced the difference between Tty and Tes and improved the stability of measurements. The use of models to correct Tty may be possible, but results should be validated in larger studies. PMID- 26542477 TI - Paediatric palliative care: recommendations for treatment of symptoms in the Netherlands. AB - BACKGROUND: Children dying of a life threatening disease suffer a great deal at the end of life. Symptom control is often unsatisfactory, partly because many caregivers are simply not familiar with paediatric palliative care. To ensure that a child with a life-threatening condition receives high quality palliative care, clinical practice guidelines are needed. The aim of this study is to improve palliative care for children by making high quality care recommendations to recognize and relieve symptoms in paediatric palliative care. METHODS: An extensive search was performed for guidelines and systematic reviews on paediatric palliative care up to year 2011. An expert panel combined the evidence with consensus to form recommendations on the treatment of symptoms in paediatric palliative care. RESULTS: We appraised 21 guidelines and identified 693 potentially eligible articles of which four met our inclusion criteria. None gave recommendations on the treatment of symptoms in paediatric palliative care. Two textbooks and an adult palliative care website were eventually our main sources of evidence. CONCLUSION: Hardly any evidence is available for the treatment of symptoms in paediatric palliative care. By combining evidence for adult palliative care and the sparse evidence for paediatric palliative care with expert opinion we defined a unique set of high quality care recommendations to relieve symptoms and lessen the suffering of children in palliative care. These results are an important tool to educate caregivers on how to relieve symptoms in children in paediatric palliative care. PMID- 26542478 TI - Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a disease often manifests in mid to late pregnancy with symptoms including hyperglycemia, insulin resistance and fetal mal-development. The C57BL/KsJ-Lep (db/+) (db/+) mouse is a genetic GDM model that closely mimicked human GDM symptoms. Resveratrol (RV) is a naturally existing compound that has been reported to exhibit beneficial effects in treating type-2 diabetes. METHODS: In this study, we investigated the effect of RV on the pregnant db/+ GDM mouse model, and the underlying molecular mechanism. RESULTS: RV greatly improved glucose metabolism, insulin tolerance and reproductive outcome of the pregnant db/+ females. Moreover, we found that RV relieved GDM symptoms through enhancing AMPK activation, which in turn reduced production and activity of glucose-6-phosphatase in both pregnant db/+ females and their offspring. CONCLUSIONS: Our findings further supported the potential therapeutic effect of RV on not only diabetes, but also alleviating GDM. PMID- 26542479 TI - Giant ribbon-like platelets mimicking microfilaria in a JAK2-positive myeloproliferative neoplasm. PMID- 26542480 TI - Persistent clonal chromosomal abnormalities in a chronic myeloid leukemia patient. AB - Clonal cytogenetic abnormalities (CCA) in Philadelphia chromosome (Ph)-negative cells have been reported in a small population of adult chronic myelogenous leukemia (CML) patients during the clinical course, but CCA in pediatric CML patients are rarely reported. We herein report the case of an 8-year-old boy from the onset of CML. Although he had relapse after unrelated bone marrow transplantation when 9 years old, he has since been in complete molecular response on imatinib mesylate treatment. Surprisingly, various CCA have been observed in this patient, including several reciprocal chromosomal translocations in Ph-negative cells for >12 years. Although dysplasia in the bone marrow cells was identified, no overt transformation to myelodysplastic syndrome or acute myeloid leukemia has been observed. The cause of the CCA remains unknown in this patient, and careful observation is required. PMID- 26542481 TI - Osteogenesis imperfecta. AB - Osteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation. PMID- 26542482 TI - Overexpression of uncoupling protein-2 in cancer: metabolic and heat changes, inhibition and effects on drug resistance. AB - This paper deals with the role of uncoupling protein-2 (UCP2) in cancer. UCP2 is overexpressed in cancer. This overexpression results in uncoupling of mitochondrial oxidative phosphorylation and a shift in production of ATP from mitochondrial oxidative phosphorylation to cytosolic aerobic glycolysis. UCP2 overexpression results in the following changes. Mitochondrial membrane potential (Deltapsi(m)) is decreased and lactate accumulates. There is a diminished production of reactive oxygen species and apoptosis is inhibited post-exposure to chemotherapeutic agents. There is an increase in heat and entropy production and a departure from the stationary state of non-cancerous tissue. Uncoupling of oxidative phosphorylation may also be caused by protonophores and non-steroidal anti-inflammatory drugs. UCP2 requires activation by superoxide and lipid peroxidation derivatives. As vitamin E inhibits lipid peroxidation, it might be expected that vitamin E would act as a chemotherapeutic agent against cancer. A recent study has shown that vitamin E and another anti-oxidant accelerate cancer progression. UCP2 is inhibited by genipin, chromane compounds and short interfering RNAs (siRNA). Genipin, chromanes and siRNA are taken up by both cancer and non-cancerous cells. Targeting the uptake of these agents by cancer cells by the enhanced permeability and retention effect is considered. Inhibition of UCP2 enhances the action of several anti-cancer agents. PMID- 26542483 TI - Back muscle fatigue of younger and older adults with and without chronic low back pain using two protocols: A case-control study. AB - The purpose of this study was to compare back muscle fatigue of younger and older participants with and without chronic low back pain (CLBP). Twenty participants without and 20 with nonspecific CLBP participated in this study. Each group contained 10 younger (50% males; mean age: 31 +/- 6 yrs) and 10 older adults (50% males; age mean: 71 +/- 7 yrs). Two isometric fatigue protocols were presented randomly: (1) to maintain the unsupported trunk at the horizontal position while on a 45 degrees Roman chair for a minute, and (2) to maintain a 10% of body weight box close to the trunk in the upright position for a minute. Surface electromyography (EMG) signals from the back (multifidus and iliocostalis) and one hip (biceps femoris) muscles were recorded bilaterally, and the median frequency fatigue estimate from linear regression slopes of the EMG time-series was computed. There were no significant (P > 0.05) age effects, and group-by-age interaction in both isometric and functional fatigue tasks. However, the CLBP groups (both younger and old) displayed more back fatigue than people without CLBP in both fatigue protocols (P < 0.01; effect size varying of d = 0.17-0.32). This study was sensitive to discriminate that individuals with CLBP did present significantly more pronounced EMG back fatigue than people without CLBP, in both younger and older adults. These results have significant clinical implications for low back pain rehabilitation programs with regard to endurance assessment in both younger and older. PMID- 26542484 TI - Hip joint motion and gluteal muscle activation differences between healthy controls and those with varying degrees of hip osteoarthritis during walking. AB - PURPOSE: Compare gluteal muscle activation patterns and three-dimensional hip joint movements among those with severe hip osteoarthritis (OA), moderate OA and a healthy group during walking. SCOPE: 20 individuals with severe OA, 20 with moderate OA and 20 healthy individuals were recruited. Three-dimensional hip motion and surface electromyograms from gluteus maximus and medius were collected during treadmill walking at a self-selected speed. Angular displacement characteristics were calculated for three-dimensional hip motions. Principal component analysis extracted amplitude and temporal features from electromyographic waveforms. Analysis of Variance models and student t-tests using Bonferroni corrections determined between group differences in these gait features (alpha = 0.05). CONCLUSIONS: Sagittal plane hip range of motion was significantly reduced with increasing severity of OA (p < 0.05) where as frontal and transverse plane range of motion was reduced in the severe OA group only (p < 0.05). Activation patterns of gluteus medius and maximus did not differ between the healthy group and those with moderate hip OA (p > 0.05). Individuals with severe OA walking with more prolonged gluteus maximus activation and prolonged and less dynamic gluteus medius activation compared to the other two groups (p < 0.05). This study highlights the changing function of the hip joint during walking with increasing hip OA severity. PMID- 26542485 TI - Neuromuscular and physiological variables evolve independently when running immediately after cycling. AB - During the early period of running after cycling, EMG patterns of the leg are modified in only some highly trained triathletes. The majority of studies have analysed muscle EMG patterns at arbitrary, predetermined time points. The purpose of this study was to examine changes to EMG patterns of the lower limb at physiologically determined times during the cycle-run transition period to better investigate neuromuscular adaptations. Six highly trained triathletes completed a 10 m in isolated run (IR), 30 min of rest, then a 20 min cycling procedure, before a 10 min transition run (C-R). Surface EMG activity of eight lower limb muscles was recorded, normalised and quantified at four time points. Oxygen uptake and heart rate values were also collected. Across all muscles, mean (+/- SD) EMG patterns, demonstrated significant levels of reproducibility for each participant at all four time points (alpha < 0.05; r = 0.52-0.97). Mean EMG patterns during C-R correlated highly with the IR patterns (alpha < 0.05). These results show that EMG patterns during subsequent running are not significantly affected by prior cycling. However, variability of muscle recruitment activity does appear to increase during C-R transition when compared to IR. PMID- 26542486 TI - Bronchiectasis is increasing in the UK, study shows. PMID- 26542487 TI - Topochemical Transformations of CaX2 (X=C, Si, Ge) to Form Free-Standing Two Dimensional Materials. AB - Topochemical transformations of layered materials CaX2 (X=Si, Ge) are the method of choice for the high-yield synthesis of pristine, defect-free two-dimensional systems silicane and germanane, which have advanced electronic properties. Based on solid-state dispersion-corrected calculations, mechanisms for such transformations are elucidated that provide an in-depth understanding of phase transition in these layered materials. While formation of such layered materials is highly favorable for silicane and germanane, a barrier of 1.2 eV in the case of graphane precludes its synthesis from CaC2 topochemically. The energy penalty required for distorting linear acetylene into a trans-bent geometry accounts for this barrier. In contrast it is highly favorable in the heavier analogues, resulting in barrierless topochemical generation of silicane and germanane. Photochemical generation of the trans-bent structure of acetylene in its first excited state (S1 ) can directly generate graphane through a barrierless condensation. Unlike the buckled structure of silicene, the phase-h of CaSi2 with perfectly planar silicene layers exhibits the Dirac cones at the high symmetry points K and H. Interestingly, topochemical acidification of the cubic phase of calcium carbide is predicted to generate the previously elusive platonic hydrocarbon, tetrahedrane. PMID- 26542488 TI - Effect of salt intake on blood pressure in patients receiving antihypertensive therapy: Shimane CoHRE Study. AB - BACKGROUND: Salt intake is recognized as an important risk factor for hypertension in the general population. On the other hand, the availability of various classes of antihypertensive drugs means that it is generally not considered crucial to control the salt intake of hypertensive patients. In this study, we evaluated whether blood pressure (BP) was correlated with 24-hour salt intake in patients receiving antihypertensive therapy. METHODS: A total of 1496 consecutive participants undergoing health screening examinations were recruited. Subjects were divided into two groups according to their antihypertensive medications checked on prescriptions: 1005 subjects without antihypertensive therapy (untreated subjects) and 491 subjects with antihypertensive therapy (treated subjects). The 24-hour urinary sodium excretion (24h-uNa), a surrogate marker for daily salt intake, was estimated with the formula proposed by Tanaka et al. in 2002. RESULTS: Univariate analysis indicated that 24h-uNa was positively correlated with the systolic BP of both untreated and treated subjects. This was confirmed by multiple linear regression analysis after adjustment for confounding factors (untreated subjects: partial regression coefficient beta=1.45 +/- 0.26, p<0.001; treated subjects: beta=0.75 +/- 0.27, p=0.01). Salt intake was also correlated with the pulse pressure in both treated subjects (beta=0.55 +/- 0.24, p=0.02) and untreated subjects (beta=0.93 +/- 0.19, p<0.001). CONCLUSION: These results suggest the importance of reducing salt intake in hypertensive patients on pharmacotherapy, as well as in the general population. Further studies of hypertensive patients employing 24-h urine collection are warranted to confirm the present findings. PMID- 26542489 TI - Is the Mediterranean diet a feasible approach to preserving cognitive function and reducing risk of dementia for older adults in Western countries? New insights and future directions. AB - The rise in the ageing population has resulted in increased incident rates of cognitive impairment and dementia. The subsequent financial and societal burden placed on an already strained public health care system is of increasing concern. Evidence from recent studies has revealed modification of lifestyle and dietary behaviours is, at present, the best means of prevention. Some of the most important findings, in relation to the Mediterranean diet (MedDiet) and the contemporary Western diet, and potential molecular mechanisms underlying the effects of these two diets on age-related cognitive function, are discussed in this review. A major aim of this review was to discuss whether or not a MedDiet intervention would be a feasible preventative approach against cognitive decline for older adults living in Western countries. Critical appraisal of the literature does somewhat support this idea. Demonstrated evidence highlights the MedDiet as a potential strategy to reduce cognitive decline in older age, and suggests the Western diet may play a role in the aetiology of cognitive decline. However, strong intrinsic Western socio-cultural values, traditions and norms may impede on the feasibility of this notion. PMID- 26542490 TI - Coming to life: The study of out-of-hospital cardiac arrest. PMID- 26542491 TI - Effects of liraglutide on left ventricular function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - BACKGROUND: Several studies have shown that exenatide protects against ischemia reperfusion injury and improves cardiac function in patients with acute ST segment elevation myocardial infarction (STEMI). The effects of liraglutide, a glucagon-like peptide-1 analogue, on STEMI patients remain unclear. We planned to evaluate the effects of liraglutide on left ventricular function after primary percutaneous coronary intervention for STEMI. METHODS: A total of 92 patients were randomized 1:1 to receive either liraglutide or placebo for 7 days. Study treatment was commenced 30 minutes before intervention (1.8 mg) and maintained for 7 days after the procedure (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days). Eighty-five patients completed the trial. Transthoracic echocardiography was used to assess left ventricular function. RESULTS: At 3 months, the primary end point, a difference in change of left ventricular ejection fraction between the two groups was +4.1% (95% CI +1.1% to +6.9%) (P < .001). There was a tendency for a lower rate of no-reflow in liraglutide group that did not reach statistical significance (7% vs control group 15%, P = .20). Liraglutide could significantly improve stress hyperglycemia (P < .05). In addition, liraglutide elicited favorable changes in markers of inflammation and endothelial function. CONCLUSION: A short 7-day course of liraglutide in STEMI patients treated with primary percutaneous coronary intervention is associated with mild improvement in left ventricular ejection fraction at 3 months. PMID- 26542492 TI - Effectiveness of cardiac rehabilitation among older patients after acute myocardial infarction. AB - BACKGROUND: Guidelines recommend cardiac rehabilitation after acute myocardial infarction, yet little is known about the impact of cardiac rehabilitation on medication adherence and clinical outcomes among contemporary older adults. The optimal number of cardiac rehabilitation sessions is not clear. METHODS: We linked patients 65years or older enrolled in the Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry GWTG) from January 2007 to December 2010 to Medicare longitudinal claims data to obtain 1 year follow-up. RESULTS: A total of 11,862 patients participated in cardiac rehabilitation after acute myocardial infarction, attending a median number of 26 sessions. Patients attending >=26 sessions were more likely to be male, had lesser prevalence of comorbid conditions and prior revascularization, and were more likely to present with ST-segment elevation myocardial infarction, compared with patients attending 1 to 25 sessions. Among patients with Medicare Part D prescription coverage, increasing number of cardiac rehabilitation sessions was associated with improvement in adherence to secondary prevention medications such as P2Y12 inhibitors and beta-blockers. Each 5-session increase in participation was associated with lower mortality (adjusted hazard ratio [HR] 0.87, 95% CI 0.83-0.92) and lower overall risk of major adverse cardiac event (adjusted HR 0.69, 95% CI 0.65-0.73) and death/readmission (adjusted HR 0.79, 95% CI 0.76-0.83). CONCLUSIONS: In this older patient population, number of cardiac rehabilitation sessions attended was associated with improved medication adherence and lower downstream cardiovascular risk in a dose-response relationship. This provides support for the continued use of cardiac rehabilitation for older adults and encourages efforts to maximize attendance. PMID- 26542493 TI - Design and rationale for the Patient and Provider Assessment of Lipid Management (PALM) registry. AB - BACKGROUND: Despite improvements in diagnosis and treatment, the prevalence of hyperlipidemia among adults in the United States remains high. Data are limited on treatment patterns and patient perceptions of cardiovascular disease risk since the release of new lipid guidelines. OBJECTIVES: The objectives of the PALM registry are to assess contemporary patterns of lipid-lowering therapy use among adults receiving care in a nationally representative cohort of community clinics, determine consistency of treatment with varying lipid guidelines, identify factors affecting use of lipid-lowering therapy including patient-reported statin intolerance, and assess patient and provider knowledge of cardiovascular risk reduction goals. STUDY DESIGN: The PALM registry will enroll 7,500 patients likely to be considered for lipid-lowering therapy from 175 cardiology, primary care, and endocrinology practices across the United States. In this cross sectional, observational registry, a novel tablet-based platform will be used to collect patient-reported knowledge, attitudes, and beliefs regarding cardiovascular risk reduction and lipid management. Chart abstraction and core laboratory lipid levels will describe current lipid management. Provider surveys will assess perception of current lipid-lowering goals and barriers to optimal cardiovascular risk reduction. CONCLUSION: The PALM registry will allow for better understanding of current practice patterns, patient experiences, and patient and provider attitudes toward cholesterol management for cardiovascular disease risk reduction. These data can be used to better understand gaps in care and design targeted interventions to improve uptake of lipid-lowering therapies for cardiovascular risk reduction. PMID- 26542494 TI - Percutaneous left ventricular assist device for high-risk percutaneous coronary interventions: Real-world versus clinical trial experience. AB - BACKGROUND: High-risk percutaneous coronary intervention (PCI) supported by percutaneous left ventricular assist devices offers a treatment option for patients with severe symptoms, complex and extensive coronary artery disease, and multiple comorbidities. The extrapolation from clinical trial to real-world practice has inherent uncertainties. We compared the characteristics, procedures, and outcomes of high-risk PCI supported by a microaxial pump (Impella 2.5) in a multicenter registry versus the randomized PROTECT II trial (NCT00562016). METHODS: The USpella registry is an observational multicenter voluntary registry of Impella technology. A total of 637 patients treated between June 2007 and September 2013 were included. Of them, 339 patients would have met enrollment criteria for the PROTECT II trial. These were compared with 216 patients treated in the Impella arm of PROTECT II. RESULTS: Compared to the clinical trial, registry patients were older (70 +/- 11.5 vs 67.5 +/- 11.0 years); more likely to have chronic kidney disease (30% vs 22.7%), prior myocardial infarction (69.3% vs 56.5%), or prior bypass surgery (39.4% vs. 30.2%); and had similar prevalence of diabetes, peripheral vascular disease, and prior stroke. Registry patients had more extensive coronary artery disease (2.2 vs 1.8 diseased vessels) and had a similar Society of Thoracic Surgeons predicted risk of mortality. At hospital discharge, registry patients experienced a similar reduction in New York Heart Association class III to IV symptoms compared to trial patients. Registry patients had a trend toward lower in-hospital mortality (2.7% vs 4.6, P = .27). CONCLUSIONS: USpella provides a real-world and contemporary estimation of the type of procedures and outcomes of high-risk patients undergoing PCI supported by Impella 2.5. Despite the higher risk of registry patients, clinical outcomes appeared to be favorable and consistent compared with the randomized trial. PMID- 26542495 TI - Radial versus femoral access for elderly patients with acute coronary syndrome undergoing coronary angiography and intervention: insights from the RIVAL trial. AB - BACKGROUND: Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization. METHODS AND RESULTS: The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were >=75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients >=75 years of age (3.6% vs 6.6%; P = .03) and in patients <75 years of age (1.0% vs 3.2%; P < .001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients >=75 (12.5% vs 2.6%; P < .001) and <75 (6.7% vs 1.9%; P < .001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients >=75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3). CONCLUSIONS: Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access. PMID- 26542496 TI - Psychosocial characteristics and outcomes in patients with left ventricular assist device implanted as destination therapy. AB - BACKGROUND: Psychosocial factors impact survival in patients undergoing cardiac transplantation, but it is unclear whether they affect outcomes in patients undergoing left ventricular assist device (LVAD) implantation as destination therapy (DT). METHODS: Patients undergoing DT LVAD at the Mayo Clinic in Rochester, MN, from February 2007 to December 2013 were included. Psychosocial characteristics at the time of LVAD implantation were abstracted from the medical record. Andersen-Gill and Cox models were used to examine the association between psychosocial characteristics and all-cause readmission and death, respectively. Patients were censored at death or last follow-up through September 2014. RESULTS: Among 136 patients (mean age. 64 years; 17% female), most were married/living with a partner (82%), half (55%) had post-high school education, and a history of depression was common (32%). Although most patients were former tobacco users (60%) only a small proportion were current tobacco users (10%) and had a history of alcohol abuse (16%) or illegal drug use (7%). After a mean follow-up of 2.2 +/- 1.8 years, 78% of patients had been readmitted (range, 0-14 per person) and 49% had died. There were no statistically significant differences in the risk of death according to psychosocial characteristics. However, current tobacco users had lower risk of readmission (adjusted HR, 0.57; 95% CI, 0.38 0.88), while illegal drug use (HR, 1.55; 95% CI, 1.01-2.35) and depression (HR, 1.77; 95% CI, 1.40-2.22) were associated with higher readmission risk. CONCLUSIONS: Psychosocial characteristics are not significant predictors of death but are associated with readmission risk after DT LVAD. PMID- 26542497 TI - Type 1 and type 2 diabetes mellitus and risk of acute kidney injury after coronary artery bypass grafting. AB - BACKGROUND: Our objective was to investigate the association between type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and acute kidney injury (AKI) in patients who underwent coronary artery bypass grafting (CABG). METHODS: We included all patients (n = 36,106) from the SWEDEHEART register who underwent primary isolated CABG in Sweden from 2003 to 2013. Information on type of diabetes was retrieved from the Swedish National Diabetes Register. Acute kidney injury was defined as an absolute increase by 0.3 mg/dL (26 MUmol/L) or a relative increase by at least 50% in postoperative serum creatinine compared with preoperative levels. Odds ratios with 95% CIs for AKI in patients with T1DM and T2DM were compared with those patients without diabetes using logistic regression. RESULTS: In total, there were 457 patients (1.3%) with T1DM and 5124 (14%) with T2DM. Among patients with T1DM and T2DM, 145 (32%) and 1037 (20%), respectively, developed AKI, compared with 4017 (13%) in patients without diabetes. The adjusted odds ratio for AKI was 4.89 (95% CI 3.82-6.25) in patients with T1DM and 1.27 (95% CI 1.16-1.40) in patients with T2DM, in comparison with patients without diabetes. CONCLUSIONS: Both T1DM and T2DM were associated with an increased risk of AKI after CABG. The risk was markedly higher in patients with T1DM than in those with T2DM and was independent of preoperative renal function. PMID- 26542498 TI - Cluster randomized controlled trial of Delayed Educational Reminders for Long term Medication Adherence in ST-Elevation Myocardial Infarction (DERLA-STEMI). AB - BACKGROUND: Discontinuation of guideline-recommended cardiac medications post-ST elevation myocardial infarction (STEMI) is common and associated with increased mortality. DERLA-STEMI tested an intervention to improve long-term adherence to cardiac medications post-STEMI. METHODS AND RESULTS: Between September 2011 and December 2012, STEMI patients from one health region in Ontario, who underwent an angiogram during their admission and survived to discharge, were cluster randomized (by primary care provider) to intervention or control. The intervention was an automated system of personalized, educational-reminders sent to the patient and their family physician, urging long-term use of secondary prevention medications. Interventions were mailed at 1, 2, 5, 8, and 11 months after discharge. A total of 852 eligible participants were randomized to intervention (n = 424, 287 clusters) and control (n = 428, 295 clusters); 87% completed a 12-month follow-up. The primary outcome, defined as the proportion of participants taking (persistence) all 4-cardiovascular medication classes (acetylsalicylic acid, angiotensin blockers, statin, and beta-blocker) at 12 months, was 58.4% (intervention) and 58.9% (control; adjusted odds ratio 1.03, 95% CI 0.77-1.36). Medication adherence, as assessed by the Morisky Medication Adherence Score, was statistically significantly better in the intervention group as compared with control (65.3% vs 58.0%, adjusted odds ratio 1.35, 95% CI 1.01 1.81). CONCLUSION: The results suggest suboptimal use of 4 of 4 cardiac medication classes at 12 months. There was no significant difference compared with usual care in the persistence to guideline-recommended medications post STEMI when participants (and their family physicians) receive repeated postal reminders. PMID- 26542499 TI - Real-time physiologic biomarker for prediction of atrial fibrillation recurrence, stroke, and mortality after electrical cardioversion: A prospective observational study. AB - BACKGROUND: Left atrial appendage emptying flow velocity (LAAEV) depends largely on left atrioventricular compliance and may play a role in mediating the perpetuation of atrial fibrillation (AF) and AF-related outcomes. METHODS: We identified 3,251 consecutive patients with sustained AF undergoing first-time successful transesophageal echocardiography (TEE)-guided electrical cardioversion who were enrolled in a prospective registry between May 2000 and March 2012. Left atrial appendage emptying flow velocity was stratified into quartiles: <=20.2, 20.3-33.9, 34-49.9, and >=50 cm/s. Multivariate Cox regression models were used to identify independent predictors of AF recurrence, ischemic stroke, and all cause mortality. RESULTS: The mean (SD) age was 69 (12.6) years and 67% were men. Compared with the fourth quartile, patients in the first-third quartiles were significantly older, had higher CHA2DS2-VASc (congestive heart failure, hypertension, age >=75 years, diabetes mellitus, stroke/transient ischemic attack [TIA], vascular disease, age 65-74 years, sex category) scores, greater frequency of atrial spontaneous echo contrast, and AF of longer duration. Kaplan-Meier analysis showed a decreased probability of event-free survival with decreasing quartiles of LAAEV. Five-year cumulative event rates across first-fourth quartiles were 83%, 80%, 73%, and 73% (P < .001) for first AF recurrence; 7.5%, 7.0%, 4.1%, and 4.0%, for stroke (P = .01); and 31.3%, 26.1%, 24.1%, and 19.4%, for mortality (P < .001), respectively. Multivariate Cox regression analysis revealed an independent association of the first and second quartiles with AF recurrence (P < .001 and P < .001, respectively) and stroke (P = .03, and P = .04, respectively), and of the first quartile with mortality (P = .003). CONCLUSIONS: Patients with decreased LAAEV have an increased risk of AF recurrence, stroke, and mortality after successful electrical cardioversion. Real time measurement of LAAEV by TEE may be a useful physiologic biomarker for individualizing treatment decisions in patients with AF. PMID- 26542500 TI - Prediabetes and the association with unrecognized myocardial infarction in the multi-ethnic study of atherosclerosis. AB - BACKGROUND: With one-quarter of initial myocardial infarctions (MI) being unrecognized MI (UMI), recognition is critical to minimize further cardiovascular risk. Diabetes mellitus is an established risk factor for UMI. If impaired fasting glucose (IFG) also increased the risk for UMI, it would represent a significant public health challenge due to the rapid worldwide increase in IFG prevalence. We compared participants with IFG to those with normal fasting glucose (NFG) to determine if IFG was associated with UMIs. METHODS: We performed cross-sectional analyses from the MESA, a population-based cohort study. There were 6,814 participants recruited during July 2000 to September 2002 from the general community at 6 field sites. After excluding those with diabetes mellitus or missing variables, 5,885 participants were included. At baseline, there were 4,955 participants with NFG and 930 participants with IFG. The main outcome was an UMI defined by the presence of pathological Q waves or minor Q waves with ST-T abnormalities on initial 12-lead electrocardiogram. Logistic regression was used to generate crude ORs and adjust for covariates. RESULTS: There was a higher prevalence of UMI in those with IFG compared with those with NFG [3.5% (n = 72) vs 1.4% (n = 30)]. After adjustment for multiple risk factors, there was a higher odds of an UMI among those with IFG compared with those with NFG [OR: 1.60 (95% CI: 1.0-2.5); P = .048]. CONCLUSIONS: Impaired fasting glucose is associated with unrecognized myocardial infarctions in a multi-ethnic population free of baseline cardiovascular disease. PMID- 26542501 TI - A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial infarction: Rationale and design of the PRESERVATION I trial. AB - Postinfarction left ventricular (LV) remodeling can result in chronic heart failure and functional impairment. Although pharmacological strategies for established heart failure can be beneficial, preventing remodeling remains a challenge. Injectable bioabsorbable alginate or "bioabsorbable cardiac matrix" (BCM), composed of an aqueous mixture of sodium alginate and calcium gluconate, is a sterile colorless liquid that is a polysaccharide polymer produced from brown seaweed. When exposed to excess ionized calcium present in infarcted myocardium, BCM assembles to form a flexible gel, structurally resembling extracellular matrix, which provides temporary structural support to the infarct zone through and beyond the time needed for mature fibrotic tissue to develop. The PRESERVATION I trial is an early phase randomized, double-blind, placebo controlled trial comparing intracoronary application of 4 mL of BCM with saline control in patients who develop large infarctions after successful reperfusion of large ST-segment elevation myocardial infarction (MI). Subjects will be randomized 2:1 to either BCM or saline control and will have the study device deployed through an intracoronary microcatheter in the infarct-related artery 2 to 5 days after index ST-segment elevation MI treated with successful primary or rescue percutaneous coronary intervention. The primary effectiveness end point is the absolute change in LV diastolic volume index as measured by 3-dimensional echocardiography from baseline to 6 months after BCM deployment. Secondary effectiveness end points include clinical outcomes, patient-reported quality of life, additional echocardiographic measures, and functional status measures. In summary, the PRESERVATION I trial is a randomized double-blind trial evaluating the effectiveness and safety of the novel device BCM in preventing LV remodeling patients who have large MIs despite undergoing successful primary or rescue percutaneous coronary intervention. PMID- 26542502 TI - Incidence and impact of delirium on clinical and functional outcomes in older patients hospitalized for acute cardiac diseases. AB - BACKGROUND: Delirium is one of the most frequent complications of hospitalization in elderly patients. Its influence on prognosis in patients admitted for acute cardiac diseases is not well known. The objective of this study is to assess the incidence of delirium and its impact on clinical and functional outcomes in older patients hospitalized for acute cardiac diseases. METHODS: We prospectively analyzed 203 patients aged 75years or older admitted to a cardiology unit. Delirium was diagnosed with the Confusion Assessment Method. Logistic regression analysis was used to assess independent predictors of in-hospital delirium and to examine the independent risk of mortality, readmission, functional decline, and need for new help at discharge, at 1month and 12months associated with the development of delirium, after adjusting for age, comorbidity, and initial diagnosis. RESULTS: The incidence of delirium was 17.2%. Patients with delirium were older (83+/-5 vs 81+/-5years, P=.016) and showed a higher prevalence of major geriatric syndromes (82.9% vs 54.5%, P=.002). Aggressive ventilation modes, urinary catheters, prolonged fluid therapy, night treatments, longer immobilization, and physical restrain were associated with the incidence of delirium. Patients with delirium presented longer stays (8.9+/-6.2 vs 6.5+/ 4.0days, P=.016) and a greater adjusted risk of functional decline at discharge (odds ratio 2.94, 95% CI 1.10-7.86, P=.032) and of 12-month mortality (odds ratio 4.20, 95% CI 1.81-9.74, P=.001). CONCLUSION: Delirium is a common preventable complication in older patients with acute cardiac diseases. It is associated with poorer in-hospital functional and clinical outcomes, and increased postdischarge mortality. PMID- 26542503 TI - Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry based randomized clinical trial. AB - BACKGROUND: Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on line platforms for randomization, case record forms, and follow-up. DESIGN/METHODS: iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1:1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality. DISCUSSION: The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR. PMID- 26542504 TI - Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model: A Web-based program designed to evaluate the cost effectiveness of disease management programs in heart failure. AB - BACKGROUND: Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. METHODS: We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying Seattle Heart Failure Model scores. The model can be used to evaluate parallel-group and single cohort study designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. RESULTS: The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. CONCLUSION: The Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure. PMID- 26542506 TI - Both processes and readmissions matter for heart failure: How can we align them? PMID- 26542505 TI - Soluble receptor for advanced glycation end products and the risk for incident heart failure: The Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. METHODS: We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. RESULTS: In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) of heart failure were 1.0 (reference), 1.81 (0.94-3.49), 1.57 (0.80-3.08), and 3.37 (1.75-6.50), for fourth, third, second, and first quartiles, respectively (P for trend = .001). We did not observe significant interactions by diabetes status or by race or obesity status. CONCLUSIONS: Lower circulating levels of sRAGE are independently associated with the development of heart failure in a community-based population. Our results add to the growing evidence that sRAGE is a valuable predictor of cardiovascular disease. PMID- 26542507 TI - Reperfusion therapy for acute myocardial infarction: Concepts and controversies from inception to acceptance. AB - More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using fibrinolytic therapy, explored in 1958, because they no longer attributed myocardial infarction to coronary thrombosis. Emergent aortocoronary bypass surgery, pioneered in 1968, remained controversial because of the misconception that hemorrhage into reperfused myocardium would result in infarct extension. Attempts to limit infarct size by pharmacotherapy without reperfusion dominated research in the 1970s. Myocardial necrosis was assumed to progress slowly, in a lateral direction. At least 18 hours was believed to be available for myocardial salvage. Afterload reduction and improvement of the microcirculation, but not reperfusion, were thought to provide the benefit of streptokinase therapy. Finally, coronary vasospasm was hypothesized to be the central mechanism in the pathogenesis of AMI. These misconceptions unraveled in the late 1970s. Myocardial necrosis was shown to progress in a transmural direction, as a "wave front," beginning with the subendocardium. Reperfusion within 6 hours salvaged a subepicardial ischemic zone in experimental animals. Acute angiography provided in vivo evidence of the high incidence of total coronary occlusion in the first hours of AMI. In 1978, early reperfusion by transluminal recanalization was shown to be feasible. The pathogenetic role of coronary thrombosis was definitively established in 1979 by demonstrating that intracoronary streptokinase rapidly restored flow in occluded infarct-related arteries, in contrast to intracoronary nitroglycerine which rarely did. The modern reperfusion era had dawned. PMID- 26542508 TI - Ticagrelor or prasugrel versus clopidogrel in elderly patients with an acute coronary syndrome: Optimization of antiplatelet treatment in patients 70 years and older--rationale and design of the POPular AGE study. AB - RATIONALE: Dual antiplatelet therapy with acetylsalicylic acid in combination with a more potent P2Y12- inhibitor (ticagrelor or prasugrel) is recommended in patients with acute coronary syndrome without ST-segment elevation (NSTE-ACS) to prevent atherothrombotic complications. The evidence on which this recommendation is based shows that ticagrelor and prasugrel reduce atherothrombotic events at the expense of an increase in bleeding events when compared with clopidogrel. However, it remains unclear whether ticagrelor or prasugrel has a better net clinical benefit in elderly patients with NSTE-ACS when compared with clopidogrel. The POPular AGE trial is designed to address the optimal antiplatelet strategy in elderly NSTE-ACS patients. STUDY DESIGN: POPular AGE is a multicenter, open-label, randomized controlled trial that aims to include 1000 patients >=70years of age with NSTE-ACS. Patients are randomly assigned to receive either clopidogrel or a more potent P2Y12 inhibitor (ticagrelor or prasugrel). The first primary end point is any bleeding event requiring medical intervention. The second primary end point is the net clinical benefit, a composite of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, "PLATelet inhibition and patient Outcomes" major bleeding, or "PLATelet inhibition and patient Outcomes" minor bleeding. Patients will be followed for 1 year after randomization, and analyses will be performed on the basis of intention to treat. CONCLUSION: The POPular AGE is the first randomized controlled trial that will assess whether the treatment strategy with clopidogrel will result in fewer bleeding events without compromising the net clinical benefit in patients >=70years of age with NSTE-ACS when compared with a treatment strategy with ticagrelor or prasugrel. PMID- 26542509 TI - Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial. AB - BACKGROUND: Resistant hypertension (RH) is a growing health burden in this country affecting as many as 1 in 5 adults being treated for hypertension. Resistant hypertension is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure (BP) in this high-risk population are a national priority. METHODS: TRIUMPH is a single-site, prospective, randomized clinical trial to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie Dietary Approaches to Stop Hypertension eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (n = 150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic BP; secondary end points include ambulatory BP and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, BP, and CVD risk factors also will be measured at 1 year follow-up. CONCLUSIONS: The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on BP and CVD biomarkers in patients with RH after 4 months of treatment and will determine whether lifestyle changes can be maintained for a year. PMID- 26542510 TI - A cluster randomized trial of objective risk assessment versus standard care for acute coronary syndromes: Rationale and design of the Australian GRACE Risk score Intervention Study (AGRIS). AB - BACKGROUND: Assessing risk and weighing the potential benefits from evidence based therapies are essential in the clinical decision making process of optimizing care and outcomes for patients presenting with acute coronary syndromes (ACS). Such practices are advocated in international clinical guidelines of ACS care. While the GRACE risk score (GRS) is a guideline advocated, well-validated risk stratification tool, its utility in improving care and outcomes remains unproven, and its application has been limited in routine clinical practice. OBJECTIVE: This study will assess the effectiveness using the GRS tool and treatment recommendations during patient assessment on improving the application of guideline-recommended therapies in ACS care. DESIGN: This study employs a PROBE (prospective cluster [hospital-level] randomized open-label, blinded endpoint) design to evaluate objective measures of hospital performance, with clinical events adjudicated by a blinded event committee. This randomized study is nested within the established CONCORDANCE registry of ACS patients, with existing methods for data collection and monitoring of care and clinical outcomes. The hospital-level intervention is the integration of the GRS into routine ACS patient assessment process. The study will assess the use of early invasive management, prescription of guideline recommended pharmacology and referral to cardiac rehabilitation by hospital discharge; with the key composite clinical endpoint of cardiovascular death, new or recurrent myocardial infarction, in-hospital heart failure or cardiovascular readmission at 12 months. Health economic impacts of risk stratification implementation will also be evaluated. The study will recruit 3000 patients from 30 hospitals. SUMMARY: The AGRIS trial will establish the effect of routine objective risk stratification using the GRACE risk score on ACS care and clinical outcomes. PMID- 26542511 TI - A systematic review and meta-analysis on the association between quality of hospital care and readmission rates in patients with heart failure. AB - In recent years, readmission rates have been increasingly used as a measure of quality of hospital care for patients with heart failure. The aim of this systematic review is to assess the scientific evidence regarding the relation between hospital readmission rates and quality of hospital care for patients with heart failure. METHODS: We defined quality of hospital care for patients with heart failure by adhering to the performance measures developed by the American College of Cardiology (ACC)/American Heart Association (AHA). Relevant articles published in English and indexed in the bibliographic databases Embase, Medline OvidSP, Web of Science, Cochrane Central, and PubMed were reviewed. RESULTS: Of the 2,638 studies identified, 18 were included. They varied widely in their methodology, data sources used, and study populations. We found mixed but rather limited evidence that there is a relationship between the ACC/AHA process measures and the rate of readmission. Four of 10 studies showed a significant correlation of readmission rate with "angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use." Three of 9 studies showed a significant correlation between readmission rates and "evaluation of left ventricular systolic function." One of 7 studies showed a significant correlation with "smoking cessation counseling," and 2 of 8 showed a significant correlation with "providing discharge instructions." No evidence was found for a relationship between readmission rates and the performance measure "warfarin for atrial fibrillation." CONCLUSIONS: Readmission rates after heart failure are mostly not related to the evidence-based ACC/AHA in-hospital process indicators for heart failure. It is unclear whether in-hospital quality of care is the key determinate of the readmission rate or whether readmissions are likely influenced more by postdischarge care. Further research is needed to clarify whether the readmission rate is a reflection of hospital care or quality of care on a larger level, especially when it is used for a pay-for-performance scheme to measure quality of hospital care. PMID- 26542512 TI - Association of prior beta-blocker use and the outcomes of patients with out-of hospital cardiac arrest. AB - beta-Blocker therapy is one of the most commonly prescribed treatments for patients with cardiac conditions. In patients with out-of-hospital cardiac arrest (OHCA), however, recent data suggest that prior treatment with beta-blockers could be harmful by lowering the incidence of a shockable presenting rhythm. The main objective of our study was to determine the association between prior beta blocker use and mortality in OHCA patients. METHODS: An observational study was conducted using the Toronto Rescu Epistry database that captured consecutive OHCA patients from 2005 to 2010. Patients older than 65 years with nontraumatic cardiac arrest and attempted resuscitation were included. Patients prescribed beta-blockers within 90 days of the arrest were compared with those without such therapy. The primary outcome was all-cause mortality at 30 days. Potential confounders were accounted for by inverse probability of treatment weighting using the propensity score. RESULTS: The median age of 8,266 OHCA patients was 79 years, 41% were women, and 2,911 (35.2%) were prescribed a beta-blocker prior to cardiac arrest. Patients prescribed beta-blockers were more likely to have existing cardiac risk factors and cardiovascular conditions. In the propensity weighted cohort, there were no differences in the presenting rhythm, with 18.4% of patients in the beta-blocker group having a shockable rhythm vs 17.5% in the no beta-blocker group (standardized difference .023). In addition, 30-day mortality was not significantly different between patients prescribed beta blockers and no beta-blockers (95.6% vs 95.1%, P = .36). CONCLUSION: beta-Blocker use was not associated with lower rates of shockable rhythms or mortality among older patients with OHCA. PMID- 26542513 TI - Impact of prasugrel pretreatment and timing of coronary artery bypass grafting on clinical outcomes of patients with non-ST-segment elevation myocardial infarction: From the A Comparison of Prasugrel at PCI or Time of Diagnosis of Non ST-Elevation Myocardial Infarction (ACCOAST) study. AB - OBJECTIVES: We evaluated impact of timing of coronary artery bypass grafting (CABG) and prasugrel pretreatment in patients with non-ST-segment elevation myocardial infarction undergoing CABG in the ACCOAST study. METHODS: Of 4033 enrolled patients, 314 (7.8%) underwent isolated CABG through 30 days. Primary efficacy end point for this analysis was any cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor bailout through 30 days. RESULTS: More CABG versus percutaneous coronary intervention or medically managed patients were men, diabetic, or had peripheral arterial disease. Per randomization, 157 of 314 patients received a 30-mg prasugrel loading dose before CABG, and 157 of 314 received placebo. Patients were stratified by tertile of time from randomization to CABG: <2.98 days (n = 104), >=2.98 and <6.95 days (n = 106), and >=6.95 days (n = 104). Primary end point occurred in 12.5%, 4.7%, and 4.8%, respectively (<2.98 days vs other tertiles, hazard ratio [HR] = 2.80; P = .011). Similarly, the rate of all TIMI major bleeding was highest in the lowest tertile (26.0% vs 10.4% and 4.8%; P < .001), but no difference in all-cause death was observed through 30 days (3.9% vs 1.9% and 1.9%; P = .30). Time from randomization to CABG (HR = 0.84 for each day delay), left main disease (HR = 1.76), region of enrollment (Non-Eastern Europe vs Eastern Europe; HR = 3.83), but not prasugrel pretreatment and baseline troponin >=3* upper limit of normal, were independent predictors of combined 30 day end point of all-cause death/myocardial infarction/stroke/TIMI major bleeding. CONCLUSIONS: In ACCOAST, early (<2.98 days) surgical revascularization carried increased risk of bleeding and ischemic complications without affecting all-cause mortality through 30 days. Baseline troponin and prasugrel pretreatment did not impact ischemic clinical outcomes. PMID- 26542514 TI - Amiodarone and risk of death in contemporary patients with atrial fibrillation: Findings from The Retrospective Evaluation and Assessment of Therapies in AF study. AB - BACKGROUND: There are limited data on mortality outcomes associated with use of amiodarone in atrial fibrillation and flutter (AF). METHODS: We evaluated the association of amiodarone use with mortality in patients with newly diagnosed AF using complete data from the Department of Veterans Affairs national health care system. We included patients seen in an outpatient setting within 90 days of a new diagnosis for nonvalvular AF between Veterans Affairs fiscal years 2004 and 2008. Multivariate analysis and propensity-matched Cox proportional hazards regression were used to evaluate the association of amiodarone use to death. RESULTS: Of 122,465 patients (353,168 person-years of follow-up, age 72.1 +/- 10.3 years, 98.4% males), amiodarone was prescribed in 11,655 (9.5%). Cumulative, unadjusted mortality rates were higher for amiodarone recipients than for nonrecipients (87 vs 73 per 1,000 person-years, P < .001). However, in multivariate and propensity-matched survival analyses, there was no significant difference in mortality (multivariate hazard ratio 1.01, 95% CI 0.97-1.05, P = .51, and propensity-matched hazard ratio 1.02, 95% CI 0.97-1.07, P = .45). The hazard of death was not modified by age, sex, heart failure, kidney function, beta-blocker use, or warfarin use, but there was evidence of effect modification among patients diagnosed with AF as an inpatient versus outpatient. CONCLUSION: In a national health care system population of newly diagnosed AF, overall use of amiodarone as an early treatment strategy was not associated with mortality. PMID- 26542515 TI - Clinical application and potential effects of 2014 hypertension guidelines on incident cardiovascular events. AB - BACKGROUND: The applicability to real-world hypertensive patients and the potential effects on future cardiovascular events of the 2014 hypertension guidelines of the Eighth Joint National Committee (JNC-8) remain to be determined. METHODS: Using the Korean National Health and Nutrition Examination Survey of 2008 to 2012 (n = 30,697), we estimated the proportion of Korean adults eligible for hypertension therapy under the 2014 JNC-8 and previous JNC-7 guidelines and the changes affected by the 2014 guidelines. Using the validation cohort (n = 116,767) from the 2003 National Health Examination with 7 years of follow-up, we determined the clinical effects of recent recommendations changes on incident cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Compared with the JNC-7 guidelines, the 2014 guidelines would decrease the number of adults eligible for hypertension therapy from 10.1 million (28.2%) to 9.3 million (25.9%). In the validation cohort, compared with nonhypertensive adults, those eligible for hypertension therapy under the JNC-7 or JNC-8 guidelines had significantly higher risks of cardiovascular events (hazard ratio [HR], 5.05; 95% confidence interval [CI], 4.58-5.57, P < 0.001; and HR, 5.11; 95% CI, 4.63-5.64, P < 0.001, respectively). In addition, adults newly ineligible for treatment under the 2014 guidelines had an increased risk of cardiovascular events relative to nonhypertensive adults (HR, 4.36; 95% CI, 3.65-5.20; P < 0.001). CONCLUSIONS: The 2014 hypertension guidelines would modestly decrease the proportion of Korean adults eligible for hypertension therapy. Adults newly ineligible for hypertension therapy by the 2014 guidelines have a higher risk of cardiovascular events compared to nonhypertensive adults. Our observations should be confirmed or refuted through large, randomized clinical trials. PMID- 26542516 TI - The MitraClip and survival in patients with mitral regurgitation at high risk for surgery: A propensity-matched comparison. AB - BACKGROUND: We compared 30-day and 1-year survival among high-risk mitral regurgitation (MR) patients treated with the MitraClip (Abbott Vascular, Abbott Park, IL) with matched non-surgically treated patients from the Duke Echocardiography Laboratory Database (DELD). METHODS AND RESULTS: High-risk patients with 3+/4+ MR managed non-surgically between years 2000 and 2010 in the longitudinal DELD were matched to high-risk MitraClip patients. Patient matching was performed using the method of nearest available Mahalanobis distance metric within calipers defined by the propensity score. Kaplan-Meier estimates and stratified Cox proportional hazards models were used to compare survival at 30 days and 1 year. Among 953 high-risk DELD patients available for matching, 30-day and 1-year mortality were 6.5% and 26.2%. Close matches were obtained for 239 of the 351 MitraClip patients. The 30-day mortality in MitraClip patients was lower (4.2%) when compared with matched DELD patients (7.2%). The 1-year relative risk of mortality of the MitraClip compared with non-surgical treatment was 0.64 (95% CI 0.45-0.91; log-rank P = .013). These results in favor of the MitraClip remained significant upon further adjustment for baseline differences between groups (P = .043). CONCLUSIONS: This matched comparison of severe MR patients at high surgical risk supports the safety of the MitraClip relative to medical therapy at 30 days and a survival benefit at 1 year. PMID- 26542517 TI - Obesity is an important source of bias in the assessment of cardiorespiratory fitness. PMID- 26542518 TI - Experimental evidence of age-related adaptive changes in human acinar airways. AB - The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID- 26542519 TI - Human Achilles tendon glycation and function in diabetes. AB - Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. Skin collagen cross-linking lysylpyridinoline, hydroxylysylpyridinoline (136%, 80%, P < 0.01) and pentosidine concentrations (55%, P < 0.05) were markedly greater in DB. Furthermore, Achilles tendon material stiffness was higher in DB (54%, P < 0.01). Notably, DB also demonstrated higher forefoot/rearfoot peak-plantar-pressure ratio (33%, P < 0.01). Overall, Achilles tendon material stiffness and skin connective tissue cross-linking were greater in diabetic patients compared with controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g., skin and joint capsule) may influence foot gait. The difference in foot pressure distribution may contribute to the development of foot ulcers in diabetic patients. PMID- 26542520 TI - Skeletal myofiber VEGF is necessary for myogenic and contractile adaptations to functional overload of the plantaris in adult mice. AB - The ability to enhance muscle size and function is important for overall health. In this study, skeletal myofiber vascular endothelial growth factor (VEGF) was hypothesized to regulate hypertrophy, capillarity, and contractile function in response to functional overload (FO). Adult myofiber-specific VEGF gene-ablated mice (skmVEGF(-/-)) and wild-type (WT) littermates underwent plantaris FO or sham surgery (SHAM). Mass, morphology, in vivo function, IGF-1, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and Akt were measured at 7, 14, and 30 days. FO resulted in hypertrophy in both genotypes, but fiber sizes were 13% and 23% smaller after 14 and 30 days, respectively, and mass 15% less after 30 days in skmVEGF(-/-) than WT. FO increased isometric force after 30 days in WT and decreased in skmVEGF(-/-) after 7 and 14 days. FO also resulted in a reduction in specific force and this differed between genotypes at 14 days. Fatigue resistance improved only in 14-day WT mice. Capillary density was decreased by FO in both genotypes. However, capillary-to-fiber ratios were 19% and 15% lower in skmVEGF(-/-) than WT at the 14- and 30-day time points, respectively. IGF-1 was increased by FO at all time points and was 45% and 40% greater in skmVEGF(-/-) than WT after 7 and 14 days, respectively. bFGF, HGF, total Akt, and phospho-Akt, independent of VEGF expression, and VEGF levels in WT were increased after 7 days of FO. These findings suggest VEGF-dependent capillary maintenance supports muscle growth and function in overloaded muscle and is not rescued by compensatory IGF-1 expression. PMID- 26542521 TI - Myriocin prevents muscle ceramide accumulation but not muscle fiber atrophy during short-term mechanical unloading. AB - Bedridden patients in intensive care unit or after surgery intervention commonly develop skeletal muscle weakness. The latter is promoted by a variety of prolonged hospitalization-associated conditions. Muscle disuse is the most ubiquitous and contributes to rapid skeletal muscle atrophy and progressive functional strength reduction. Disuse causes a reduction in fatty acid oxidation, leading to its accumulation in skeletal muscle. We hypothesized that muscle fatty acid accumulation could stimulate ceramide synthesis and promote skeletal muscle weakness. Therefore, the present study was designed to determine the effects of sphingolipid metabolism on skeletal muscle atrophy induced by 7 days of disuse. For this purpose, male Wistar rats were treated with myriocin, an inhibitor of de novo synthesis of ceramides, and subjected to hindlimb unloading (HU) for 7 days. Soleus muscles were assayed for fiber diameter, ceramide levels, protein degradation, and apoptosis signaling. Serum and liver were removed to evaluate the potential hepatoxicity of myriocin treatment. We found that HU increases content of saturated C16:0 and C18:0 ceramides and decreases soleus muscle weight and fiber diameter. HU increased the level of polyubiquitinated proteins and induced apoptosis in skeletal muscle. Despite a prevention of C16:0 and C18:0 muscle accumulation, myriocin treatment did not prevent skeletal muscle atrophy and concomitant induction of apoptosis and proteolysis. Moreover, myriocin treatment increased serum transaminases and induced hepatocyte necrosis. These data highlight that inhibition of de novo synthesis of ceramides during immobilization is not an efficient strategy to prevent skeletal muscle atrophy and exerts adverse effects like hepatotoxicity. PMID- 26542522 TI - Measuring the human ventilatory and cerebral blood flow response to CO2: a technical consideration for the end-tidal-to-arterial gas gradient. AB - Our aim was to quantify the end-tidal-to-arterial gas gradients for O2 (PET-PaO2) and CO2 (Pa-PETCO2) during a CO2 reactivity test to determine their influence on the cerebrovascular (CVR) and ventilatory (HCVR) response in subjects with (PFO+, n = 8) and without (PFO-, n = 7) a patent foramen ovale (PFO). We hypothesized that 1) the Pa-PETCO2 would be greater in hypoxia compared with normoxia, 2) the Pa-PETCO2 would be similar, whereas the PET-PaO2 gradient would be greater in those with a PFO, 3) the HCVR and CVR would be underestimated when plotted against PETCO2 compared with PaCO2, and 4) previously derived prediction algorithms will accurately target PaCO2. PETCO2 was controlled by dynamic end tidal forcing in steady-state steps of -8, -4, 0, +4, and +8 mmHg from baseline in normoxia and hypoxia. Minute ventilation (VE), internal carotid artery blood flow (QICA), middle cerebral artery blood velocity (MCAv), and temperature corrected end-tidal and arterial blood gases were measured throughout experimentation. HCVR and CVR were calculated using linear regression analysis by indexing VE and relative changes in QICA, and MCAv against PETCO2, predicted PaCO2, and measured PaCO2. The Pa-PETCO2 was similar between hypoxia and normoxia and PFO+ and PFO-. The PET-PaO2 was greater in PFO+ by 2.1 mmHg during normoxia (P = 0.003). HCVR and CVR plotted against PETCO2 underestimated HCVR and CVR indexed against PaCO2 in normoxia and hypoxia. Our PaCO2 prediction equation modestly improved estimates of HCVR and CVR. In summary, care must be taken when indexing reactivity measures to PETCO2 compared with PaCO2. PMID- 26542523 TI - Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective. AB - The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. PMID- 26542524 TI - Clinical features and treatment of patients with esophageal cancer and a history of gastrectomy: a multicenter, questionnaire survey in Kyushu, Japan. AB - It is still controversial whether patients with a history of gastrectomy have high risk of esophageal carcinogenesis. On the other hand, the treatment strategy for esophageal cancer patients after gastrectomy is complicated. The association between histories of gastrectomy and esophageal carcinogenesis was retrospectively analyzed, and the treatment of esophageal cancer patients after gastrectomy was evaluated based on questionnaire data collected from multiple centers in Kyushu, Japan. The initial subject population comprised 205 esophageal cancer patients after gastrectomy. Among them, 108 patients underwent curative surgical treatment, and 70 patients underwent chemoradiation therapy (CRT). The time between gastrectomy and esophageal cancer development was longer in peptic ulcer patients (28.3 years) than in gastric cancer patients (9.6 years). There were no differences in the location of esophageal cancer according to the gastrectomy reconstruction method. There were no significant differences in the clinical background characteristics between patients with and without a history of gastrectomy. Among the 108 patients in the surgery group, the 5-year overall survival rates for stages I (n = 30), II (n = 18), and III (n = 60) were 68.2%, 62.9%, and 32.1%, respectively. In the CRT group, the 5-year overall survival rate of stage I (n = 29) was 82.6%, but there were no 5-year survivors in other stages. The 5-year overall survival rate of patients with CR (n = 33) or salvage surgery (n = 10) was 61.2% or 36%, respectively. For the treatment of gastrectomized esophageal cancer patients, surgery or CRT is recommended for stage I, and surgery with or without adjuvant therapy is the main central treatment in advanced stages, with surgery for stage II, neoadjuvant therapy + surgery for stage III, and CRT + salvage surgery for any stage, if the patient's condition permits. PMID- 26542525 TI - miRA: adaptable novel miRNA identification in plants using small RNA sequencing data. AB - BACKGROUND: MicroRNAs (miRNAs) are short regulatory RNAs derived from longer precursor RNAs. miRNA biogenesis has been studied in animals and plants, recently elucidating more complex aspects, such as non-conserved, species-specific, and heterogeneous miRNA precursor populations. Small RNA sequencing data can help in computationally identifying genomic loci of miRNA precursors. The challenge is to predict a valid miRNA precursor from inhomogeneous read coverage from a complex RNA library: while the mature miRNA typically produces many sequence reads, the remaining part of the precursor is covered very sparsely. As recent results suggest, alternative miRNA biogenesis pathways may lead to a more diverse miRNA precursor population than previously assumed. In plants, the latter manifests itself in e.g. complex secondary structures and expression from multiple loci within precursors. Current miRNA identification algorithms often depend on already existing gene annotation, and/or make use of specific miRNA precursor features such as precursor lengths, secondary structures etc. Consequently and in view of the emerging new understanding of a more complex miRNA biogenesis in plants, current tools may fail to characterise organism-specific and heterogeneous miRNA populations. RESULTS: miRA is a new tool to identify miRNA precursors in plants, allowing for heterogeneous and complex precursor populations. miRA requires small RNA sequencing data and a corresponding reference genome, and evaluates precursor secondary structures and precursor processing accuracy; key parameters can be adapted based on the specific organism under investigation. We show that miRA outperforms the currently best plant miRNA prediction tools both in sensitivity and specificity, for data involving Arabidopsis thaliana and the Volvocine algae Chlamydomonas reinhardtii; the latter organism has been shown to exhibit a heterogeneous and complex precursor population with little cross-species miRNA sequence conservation, and therefore constitutes an ideal model organism. Furthermore we identify novel miRNAs in the Chlamydomonas-related organism Volvox carteri. CONCLUSIONS: We propose miRA, a new plant miRNA identification tool that is well adapted to complex precursor populations. miRA is particularly suited for organisms with no existing miRNA annotation, or without a known related organism with well characterized miRNAs. Moreover, miRA has proven its ability to identify species-specific miRNAs. miRA is flexible in its parameter settings, and produces user-friendly output files in various formats (pdf, csv, genome-browser-suitable annotation files, etc.). It is freely available at https://github.com/mhuttner/miRA. PMID- 26542526 TI - Mismatch negativity (MMN) as biomarker predicting psychosis in clinically at-risk individuals. AB - The early detection of young people at-risk of developing a severe mental illness like schizophrenia offers the opportunity of introducing treatment earlier than currently possible. There is some evidence that early intervention improves prognosis and functional outcome, or even prevents the full clinical manifestation of the condition in some individuals. A key prerequisite to facilitate early intervention would be a biomarker that can reliably predict a transition to schizophrenia. A smaller event-related mismatch negativity (MMN) potential has emerged as one of the most robust psychophysiological finding in schizophrenia akin of a biomarker of the condition. More recent research further demonstrates that MMN, but also P3a amplitudes, are already reduced in the prodromal phase of illness. Several lines of pre-clinical and clinical research support this notion and are reviewed in this article together with current obstacles, which are still limiting the translation of MMN as a biomarker into clinical practice. PMID- 26542527 TI - Experienced stress produces inhibitory deficits in old adults' Flanker task performance: First evidence for lifetime stress effects beyond memory. AB - Studies regarding aged individuals' performance on the Flanker task differ with respect to reporting impaired or intact executive control. Past work has explained this discrepancy by hypothesising that elderly individuals use increased top-down control mechanisms advantageous to Flanker performance. This study investigated this mechanism, focussing on cumulative experienced stress as a factor that may impact on its execution, thereby leading to impaired performance. Thirty elderly and thirty young participants completed a version of the Flanker task paired with electroencephalographic recordings of the alpha frequency, whose increased synchronisation indexes inhibitory processes. Among high stress elderly individuals, findings revealed a general slowing of reaction times for congruent and incongruent stimuli, which correlated with alpha desynchronisation for both stimulus categories. Results found high performing (low stress) elderly revealed neither a behavioural nor electrophysiological difference compared to young participants. Therefore, rather than impacting on top-down compensatory mechanisms, findings indicate that stress may affect elderly participants' inhibitory control in attentional and sensorimotor domains. PMID- 26542528 TI - Application of endoscopic ultrasonography to intraventricular lesions. AB - BACKGROUND: Anatomical landmarks such as choroid plexus and foramen of Monro are very important to undergo intraventricular surgery safely and effectually. These landmarks would be unclear in cases with a huge cyst or repeat surgery. We report the usability and precautions to apply a bronchoscope with an ultrasonic convex probe to intraventricular surgery. METHODS: Two patients diagnosed with obstructive hydrocephalus, one with a large cyst and the other with recurrent craniopharyngioma in the third ventricle, were applied to the EBUS system. RESULTS: In both patients, the EBUS system was applied safely, and lesions beyond the wall of ventricles or the cyst were visible. Color Doppler ultrasonography detected choroid plexus and internal cerebral veins. Furthermore, we performed real-time ultrasound-guided cyst puncture safely on the case with a large cyst. The most important precaution is that the curved portion of the EBUS system is too long to be bent within cerebral ventricles. CONCLUSIONS: The new EBUS system with an ultrasonic convex probe is a novel and effectual device to perform intraventricular surgery. PMID- 26542529 TI - What is a clinically relevant difference in MDADI scores between groups of head and neck cancer patients? AB - OBJECTIVE/HYPOTHESIS: To describe clinically relevant between-group differences in MD Anderson Dysphagia Inventory (MDADI) scores among head and neck cancer (HNC) patients. STUDY DESIGN: Retrospective cross-sectional study was conducted in 1,136 HNC patients seen for modified barium swallow (MBS) studies. METHODS: The MDADI was administered by written questionnaire at the MBS appointment. MD Anderson Dysphagia Inventory global, composite, and subscale scores were calculated. Anchor-based methods were employed to determine clinically meaningful between-group differences by feeding tube status, aspiration status (per MBS study), and diet level. RESULTS: Mean MDADI scores for the 1,136 patients were: emotional 65.8 +/- 17.3, functional 68.1 +/- 19.6, physical 60.1 +/- 18.6, global 59.3 +/- 28.3, and composite 64.0 +/- 17.1. Three hundred seventy-eight patients (33%) were feeding tube-dependent; 395 (34.8%) were aspirators; 122 (11%) were nothing per oral (Performance Status Scale-Head and Neck [PSS-HN] diet = 0); and 249 (22%) ate unrestricted, regular diets (PSS-HN diet = 100). Statistically significant (P < 0.0001) between-group differences (feeding tube vs. no feeding tube, aspirator vs. nonaspirator, oral vs. nonoral diet, PSS-HN diet levels) were observed for all mean MDADI scores (global, composite, and subscales). A mean difference of 10 points in composite MDADI scores differentiated feeding tube dependent from nontube-dependent patients, aspirators from nonaspirators, and distinct PSS-HN diet levels. CONCLUSIONS: We identify that a 10-point between group difference in composite MDADI scores was associated with clinically meaningful between-group differences in swallowing function. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1108-1113, 2016. PMID- 26542530 TI - Aneurinibacillus humi sp. nov., Isolated from Soil Collected in Ukraine. AB - A novel bacterium, designated U33(T), was isolated from a soil sample collected in Mykhailyky, Poltavs'ka oblast, Ukraine. The bacterium was aerobic, Gram positive, spore-forming, and consists of motile rods. The taxonomic position of strain U33(T) was studied by a polyphasic approach, and the results clearly showed that the phenotypic and chemotaxonomic properties are consistent with those of the genus Aneurinibacillus. The phylogenic analysis with 16S rRNA gene sequence of strains U33(T) showed the highest sequence similarity to those of Aneurinibacillus aneuriniticus ATCC 12856(T) (96.7 %), Aneurinibacillus migulanus DSM 2895(T) (96.7 %), Aneurinibacillus danicus NCIMB 13288(T) (95.8 %), and lower sequence similarity with other members of the genus Aneurinibacillus. Growth was observed at 20-55 degrees C (optimum, 37 degrees C) at pH 5.0-9.0 (optimum, pH 7) and with 0-5 % (w/v) NaCl (optimum, 2 % NaCl). The predominant menaquinone was MK-7 and the cell wall peptidoglycan consist of meso-diaminopimelic acid. The major cellular fatty acids are iso-C15:0 (58.0 %) and anteiso-C15:0 (13.2 %). The DNA G+C content of the strain U33(T) was 45.8 %. The physiological and chemotaxonomic characteristics distinguish strain U33(T) from the validly published species of genus Aneurinibacillus, and therefore, we consider this strain to represent a novel species of the genus Aneurinibacillus. The name Aneurinibaciilus humi sp. nov. is proposed with strain U33(T) (= KEMC7305-119(T) = JCM19865(T)) as the type strain. PMID- 26542531 TI - The Detection of Hemin-Binding Proteins in Riemerella anatipestifer CH-1. AB - Riemerella anatipestifer (R. anatipestifer) is among the most prevalent duck pathogens, causing acute or chronic septicemia characterized by serositis. Riemerella anatipestifer can be grown on blood-enriched media, in vitro, which provides a hemin source essential for the sustainment of R. anatipestifer and activation of hemin-uptake systems. However, the genes associated with hemin uptake cannot be identified exclusively through genome sequence analysis. Here, we show that R. anatipestifer encodes outer-membrane hemin-binding proteins. Hemin-binding proteins were identified in the cytoplasm with apparent molecular mass of ~45/37/33/23/20/13 kDa, and outer membrane with apparent molecular mass of ~90/70/60/50/15 kDa by batch affinity chromatography and hemin-blotting assays. Our results indicate that these proteins are involved in hemin acquisition. Finally, hemin-binding assay further showed that R. anatipestifer can bind hemin and this capability is increased in iron limited medium, indicating the hemin-uptake system of R. anatipestifer was regulated by iron. PMID- 26542532 TI - A Meta-analysis of Bacterial Diversity in the Feces of Cattle. AB - In this study, we conducted a meta-analysis on 16S rRNA gene sequences of bovine fecal origin that are publicly available in the RDP database. A total of 13,663 sequences including 603 isolate sequences were identified in the RDP database (Release 11, Update 1), where 13,447 sequences were assigned to 10 phyla, 17 classes, 28 orders, 59 families, and 110 genera, while the remaining 216 sequences could not be assigned to a known phylum. Firmicutes and Bacteroidetes were the first and the second predominant phyla, respectively. About 41 % of the total sequences could not be assigned to a known genus. The total sequences were assigned to 1252 OTUs at 97 % sequence similarity. A small number of OTUs shared among datasets indicate that fecal bacterial communities of cattle are greatly affected by various factors, specifically diet. This study may guide future studies to further analyze fecal bacterial communities of cattle. PMID- 26542533 TI - Cumulative and bidirectional association of physical activity and sedentary behaviour with health-related quality of life in adolescents. AB - BACKGROUND: The directionality of the association of physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) remains unknown in adolescents. This study aimed to investigate the association of 2-year cumulative level of PA and SB with HRQoL and the reverse association. METHODS: We included 1445 adolescents in France from a 2-year longitudinal study with three follow-up times (PRALIMAP trial). At each follow-up, adolescents completed the International Physical Activity Questionnaire for PA and SB and the Duke Health Profile for HRQoL. Statistical analyses involved linear and logistic regressions adjusted for socio-demographic characteristics. RESULTS: The cumulative number of times an adolescent achieved the PA recommendations during the 2 years was associated with better physical, mental, social and general HRQoL (p for trend < 0.0001). In contrast, high SB predicted low HRQoL for most dimensions except social HRQoL (p = 0.12). Combining PA and SB, the effect of recommended PA on HRQoL was offset in part by high SB. In the reverse association, high HRQoL predicted high PA (overall, vigorous, moderate and recommended PA), but was not associated with SB. CONCLUSIONS: The association between PA and HRQoL was cumulative and bidirectional among adolescents, whereas low HRQoL seemed to be a consequence of high SB rather than a cause (cumulative but not bidirectional). Promoting recommended PA and low SB may help improve HRQoL among adolescents, with a possible virtuous cycle with regard to PA. PMID- 26542534 TI - Assessing and targeting key lifestyle cardiovascular risk factors at the workplace: Effect on hemoglobin A1c levels. AB - PURPOSE: Despite the key role played by lifestyle habits in the epidemic of type 2 diabetes (T2D), nutritional quality and physical activity are not systematically considered in clinical practice. The project was conducted to verify whether assessing/targeting lifestyle habits could reduce hemoglobin A1c (HbA1c) levels of employees. METHODS: The intervention consisted of a 3-month competition among teams of five employees to favor peer-based support in the adoption of healthier lifestyle habits (Eat better, Move more, and Quit smoking) (n = 900). A comprehensive cardiometabolic/cardiorespiratory health assessment was conducted before and after the contest (nutrition/physical activity questionnaires, blood pressure, anthropometric measurements, lipid profile, HbA1c, fitness). HbA1c levels were used to identify individuals with prediabetes (5.7%-6.4%) or T2D (>=6.5%). RESULTS: At baseline, 51% of the employees had increased HbA1c levels (>=5.7%). The HbA1c levels were associated with waist circumference, independently of body mass index. Subjects with prediabetes showed a higher waist circumference as well as a more deteriorated cardiometabolic profile compared to workers with normal HbA1c levels. After the intervention, employees with elevated HbA1c significantly reduced their HbA1c levels. CONCLUSION: Results suggest that assessing/targeting key lifestyle correlates of the cardiometabolic profile represents a relevant approach to target abdominal obesity and fitness with a significant impact on HbA1c levels. PMID- 26542535 TI - Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody. AB - Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently dominant JEV genotypes. This study opens new therapeutic options for Japanese encephalitis. PMID- 26542536 TI - Solitary fibrous tumor of the pleura: Can computed tomography features help predict malignancy? A series of 56 patients with histopathological correlates. AB - OBJECTIVE: To identify computed tomography (CT) predictors of malignancy, from a retrospective study of preoperative CT scans of patients with solitary fibrous tumors (SFT) of the pleura. PATIENTS AND METHODS: The CT scans of 56 patients with histopathologically confirmed SFT (33 women and 23 men; mean age, 60years) who underwent surgery between December 2004 and November 2012 were retrospectively analyzed by three radiologists working in consensus, blinded to the final histological diagnosis. RESULTS: SFT was asymptomatic and incidentally discovered in 22 patients (45.8%). Resection specimen analysis (R0 resection in all cases) revealed that 23 tumors (41%) were malignant. The CT features, which significantly differed between malignant and benign SFTs were tumor size (P=0.002) with a discriminative threshold value of 10cm, tumor heterogeneity before (P=0.02) and after (P=0.03) intravenous administration of iodinated contrast material, presence of intratumoral hydric attenuation areas (P=0.01), pleural effusion (P=0.01), measurable intratumoral vessels (P=0.02), hypervascularization with visible intratumoral vessels and/or marked enhancement (P=0.001). Presence of intratumoral calcifications (P=0.2) and maximum post contrast enhancement value (P=0.6) were not significantly different between the two groups. CONCLUSION: A size greater than or equal to 10cm, hypervascularization, attenuation heterogeneity and association with pleural effusion are individual variables that suggest malignant SFT on CT. PMID- 26542538 TI - Highlight report: mitochondrial depolarization by ethanol. PMID- 26542537 TI - Molecular Characterization of Acanthamoeba spp. Occurring in Water Bodies and Patients in Poland and Redefinition of Polish T16 Genotype. AB - Acanthamoeba genus is divided into 20 genotypes (T1-T20) on the basis of the gene encoding 18S rRNA sequence. Using of at least 2 kbp gene fragments is strongly recommended to identify new genotypes and 5% difference is commonly used as a criterion of new genotypes, however, this value is questionable. In this paper, Polish Acanthamoeba strains described earlier on the basis of ~850 bp Ami fragment of 18S rRNA gene as T4, T11 and a new T16 genotype, have been analyzed using near-complete sequence of the gene. This analysis was needed because the Ami fragment does not reveal full variability within 18S rRNA gene. Phylogenetic analysis based on Ami fragment is biased by artifacts in the construction of the tree, so the fragment should not be used for identification of new putative Acanthamoeba genotypes. The analysis confirmed that the Polish sequences represent T4 and T11 genotypes and that the strains described earlier as T16 genotype are in fact a new subgroup of the T20 genotype and that this genotype should be divided into two subgroups: T20a (two strains described by [J. Eukaryot. Microbiol. 62 (2015) 69]) and T20b (11 Polish strains described in this study). The T20b subgroup was isolated from both clinical samples and water bodies used by people as bathing places and there is a risk of infection for humans during contact with water. PMID- 26542539 TI - Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases. AB - Methyleugenol is a substituted alkenylbenzene found in several herbs and spices. It is classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed the biological mechanism of the genotoxic properties of methyleugenol and its oxidative metabolites. Methyleugenol and the oxidative metabolites significantly enhanced the DNA damage in human colon carcinoma cells (HT29). Methyleugenol did not affect the protein status of gammaH2AX, a biomarker of DNA double-strand breaks, whereas its metabolites methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol significantly increased the cellular phosphorylated H2AX level. Both of these metabolites also showed a significant induction of micronuclei in HT29 cells. Furthermore, we investigated whether topoisomerase interaction contribute to the observed effect on DNA integrity. Methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol inhibited the activity of recombinant topoisomerase I. In HT29 cells, neither methyleugenol nor the metabolites affected the level of topoisomerase protein bound to DNA, excluding a topoisomerase poisoning mode of action. In addition, 3' oxomethylisoeugenol potently diminished the level of camptothecin-stabilized topoisomerase I/DNA intermediates and camptothecin-induced DNA strand breaks. In conclusion, it could be suggested that 3'-oxomethylisoeugenol may also interact with classical or food-borne topoisomerase I poisons, diminishing their poisoning effectiveness. PMID- 26542541 TI - Cover stories: From plot to finish: Visualizing martian atmospheric data from MAVEN in CINEMA 4D with Python. PMID- 26542540 TI - Integrated analysis identified genes associated with a favorable prognosis in oligodendrogliomas. AB - Oligodendrogliomas (ODs) are the second most common malignant brain tumor and exhibit characteristic co-deletion of chromosomal arms 1p and 19q (co-deletion 1p/19q), which is associated with down-regulation of tumor suppressors. However, co-deletion 1p/19q indicates a favorable prognosis that cannot be explained by the down-regulation of tumor suppressors. In the present study, we determined that co-deletion 1p/19q was associated with reduced Ki-67 protein level based on analysis of 354 ODs. To identify genes associated with reduced Ki-67 and a favorable prognosis of codeletion 1p/19q, we analyzed 96 ODs with RNA-sequencing and 136 ODs and 4 normal brain tissue samples with RNA microarrays. We thus identified seven genes within chromosomal arms 1p/19q with significantly reduced expression in samples with co-deletion of 1p/19q compared to samples with intact 1p/19q. A significant positive correlation was observed between these candidate genes and Ki-67 expression based on analysis of mRNA expression in 305 gliomas and 5 normal brain tissue samples. Survival analysis confirmed the prognostic value of these candidate genes. This finding suggests that these genes within chromosomal arms 1p/19q are associated with low Ki-67 and a favorable prognosis in ODs with co-deletion 1p/19q and provides novel therapeutic targets. PMID- 26542542 TI - Eradicating polio. PMID- 26542544 TI - GEOCHEMISTRY. How buried water makes diamonds and oil. PMID- 26542545 TI - MICROBIOME. Microbes aid cancer drugs. PMID- 26542546 TI - BEHIND THE NUMBERS. Data check: How a $30 billion hike becomes $3 billion. PMID- 26542547 TI - SCIENCE IN SOCIETY. Pacific Rim mathematicians coaxed from their ivory towers. PMID- 26542548 TI - SCIENCE POLICY. India orders premier labs to pay their own way. PMID- 26542549 TI - DEVELOPMENTAL BIOLOGY. Using evolution to better identify cell types. PMID- 26542550 TI - ONCOLOGY. Vitamin C could target some common cancers. PMID- 26542551 TI - Eggs unlimited. PMID- 26542552 TI - PUBLIC HEALTH. Dengue vaccines at a crossroad. PMID- 26542553 TI - METABOLISM. A pancreatic clock times insulin release. PMID- 26542554 TI - CHEMISTRY. Love at second sight for CO2 and H2 in organic synthesis. PMID- 26542555 TI - PHYSICS. Frustrating a quantum magnet. PMID- 26542556 TI - RESEARCH ETHICS. Evidence gaps and ethical review of multicenter studies. PMID- 26542557 TI - EPIGENETICS. The epigenome--a family affair. PMID- 26542558 TI - NUCLEAR FUELS. How to isolate americium. PMID- 26542559 TI - DRUG DISCOVERY. A new dawn for cataracts. PMID- 26542560 TI - Lift NIH restrictions on chimera research. PMID- 26542561 TI - Making sense of the troubles at NEON. PMID- 26542563 TI - MAVEN GOES TO MARS. MAVEN Explores the Martian Upper Atmosphere. Introduction. PMID- 26542564 TI - Electrochemical oxidation of 243Am(III) in nitric acid by a terpyridyl derivatized electrode. AB - Selective oxidation of trivalent americium (Am) could facilitate its separation from lanthanides in nuclear waste streams. Here, we report the application of a high-surface-area, tin-doped indium oxide electrode surface-derivatized with a terpyridine ligand to the oxidation of Am(III) to Am(V) and Am(VI) in nitric acid. Potentials as low as 1.8 volts (V) versus the saturated calomel electrode were applied, 0.7 V lower than the 2.6 V potential for one-electron oxidation of Am(III) to Am(IV) in 1 molar acid. This simple electrochemical procedure provides a method to access the higher oxidation states of Am in noncomplexing media for the study of the associated coordination chemistry and, more important, for more efficient separation protocols. PMID- 26542565 TI - Evidence for a gapped spin-liquid ground state in a kagome Heisenberg antiferromagnet. AB - The kagome Heisenberg antiferromagnet is a leading candidate in the search for a spin system with a quantum spin-liquid ground state. The nature of its ground state remains a matter of active debate. We conducted oxygen-17 single-crystal nuclear magnetic resonance (NMR) measurements of the spin-1/2 kagome lattice in herbertsmithite [ZnCu3(OH)6Cl2], which is known to exhibit a spinon continuum in the spin excitation spectrum. We demonstrated that the intrinsic local spin susceptibility chi(kagome), deduced from the oxygen-17 NMR frequency shift, asymptotes to zero below temperatures of 0.03J, where J ~ 200 kelvin is the copper-copper superexchange interaction. Combined with the magnetic field dependence of chi(kagome) that we observed at low temperatures, these results imply that the kagome Heisenberg antiferromagnet has a spin-liquid ground state with a finite gap. PMID- 26542566 TI - Creation of a low-entropy quantum gas of polar molecules in an optical lattice. AB - Ultracold polar molecules, with their long-range electric dipolar interactions, offer a unique platform for studying correlated quantum many-body phenomena. However, realizing a highly degenerate quantum gas of molecules with a low entropy per particle is challenging. We report the synthesis of a low-entropy quantum gas of potassium-rubidium molecules (KRb) in a three-dimensional optical lattice. We simultaneously load into the optical lattice a Mott insulator of bosonic Rb atoms and a single-band insulator of fermionic K atoms. Then, using magnetoassociation and optical state transfer, we efficiently produce ground state molecules in the lattice at those sites that contain one Rb and one K atom. The achieved filling fraction of 25% should enable future studies of transport and entanglement propagation in a many-body system with long-range dipolar interactions. PMID- 26542567 TI - The ecology of the microbiome: Networks, competition, and stability. AB - The human gut harbors a large and complex community of beneficial microbes that remain stable over long periods. This stability is considered critical for good health but is poorly understood. Here we develop a body of ecological theory to help us understand microbiome stability. Although cooperating networks of microbes can be efficient, we find that they are often unstable. Counterintuitively, this finding indicates that hosts can benefit from microbial competition when this competition dampens cooperative networks and increases stability. More generally, stability is promoted by limiting positive feedbacks and weakening ecological interactions. We have analyzed host mechanisms for maintaining stability-including immune suppression, spatial structuring, and feeding of community members-and support our key predictions with recent data. PMID- 26542568 TI - Corticomotoneuronal cells are "functionally tuned". AB - Corticomotoneuronal (CM) cells in the primary motor cortex (M1) have monosynaptic connections with motoneurons. They are one of the few sources of descending commands that directly influence motor output. We examined the contribution of CM cells to the generation of activity in their target muscles. The preferred direction of many CM cells differed from that of their target muscles. Some CM cells were selectively active when a muscle was used as an agonist. Others were selectively active when the same muscle was used as a synergist, fixator, or antagonist. These observations suggest that the different functional uses of a muscle are generated by separate populations of CM cells. We propose that muscle function is one of the dimensions represented in the output of M1. PMID- 26542569 TI - Plant pathogenic anaerobic bacteria use aromatic polyketides to access aerobic territory. AB - Around 25% of vegetable food is lost worldwide because of infectious plant diseases, including microbe-induced decay of harvested crops. In wet seasons and under humid storage conditions, potato tubers are readily infected and decomposed by anaerobic bacteria (Clostridium puniceum). We found that these anaerobic plant pathogens harbor a gene locus (type II polyketide synthase) to produce unusual polyketide metabolites (clostrubins) with dual functions. The clostrubins, which act as antibiotics against other microbial plant pathogens, enable the anaerobic bacteria to survive an oxygen-rich plant environment. PMID- 26542570 TI - Pharmacological chaperone for alpha-crystallin partially restores transparency in cataract models. AB - Cataracts reduce vision in 50% of individuals over 70 years of age and are a common form of blindness worldwide. Cataracts are caused when damage to the major lens crystallin proteins causes their misfolding and aggregation into insoluble amyloids. Using a thermal stability assay, we identified a class of molecules that bind alpha-crystallins (cryAA and cryAB) and reversed their aggregation in vitro. The most promising compound improved lens transparency in the R49C cryAA and R120G cryAB mouse models of hereditary cataract. It also partially restored protein solubility in the lenses of aged mice in vivo and in human lenses ex vivo. These findings suggest an approach to treating cataracts by stabilizing alpha-crystallins. PMID- 26542571 TI - Crystal structure of the anion exchanger domain of human erythrocyte band 3. AB - Anion exchanger 1 (AE1), also known as band 3 or SLC4A1, plays a key role in the removal of carbon dioxide from tissues by facilitating the exchange of chloride and bicarbonate across the plasma membrane of erythrocytes. An isoform of AE1 is also present in the kidney. Specific mutations in human AE1 cause several types of hereditary hemolytic anemias and/or distal renal tubular acidosis. Here we report the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. The structure is locked in an outward-facing open conformation by an inhibitor. Comparing this structure with a substrate-bound structure of the uracil transporter UraA in an inward-facing conformation allowed us to identify the anion-binding position in the AE1(CTD), and to propose a possible transport mechanism that could explain why selected mutations lead to disease. PMID- 26542572 TI - The Papaver rhoeas S determinants confer self-incompatibility to Arabidopsis thaliana in planta. AB - Self-incompatibility (SI) is a major genetically controlled system used to prevent inbreeding in higher plants. S determinants regulate allele-specific rejection of "self" pollen by the pistil. SI is an important model system for cell-to-cell recognition and signaling and could be potentially useful for first generation (F1) hybrid breeding. To date, the transfer of S determinants has used the complementation of orthologs to "restore" SI in close relatives. We expressed the Papaver rhoeas S determinants PrsS and PrpS in Arabidopsis thaliana. This enabled pistils to reject pollen expressing cognate PrpS. Moreover, plants coexpressing cognate PrpS and PrsS exhibit robust SI. This demonstrates that PrsS and PrpS are sufficient for a functional synthetic S locus in vivo. This transfer of novel S determinants into a highly divergent species (>140 million years apart) with no orthologs suggests their potential utility in crop production. PMID- 26542573 TI - A cucurbit androecy gene reveals how unisexual flowers develop and dioecy emerges. AB - Understanding the evolution of sex determination in plants requires identifying the mechanisms underlying the transition from monoecious plants, where male and female flowers coexist, to unisexual individuals found in dioecious species. We show that in melon and cucumber, the androecy gene controls female flower development and encodes a limiting enzyme of ethylene biosynthesis, ACS11. ACS11 is expressed in phloem cells connected to flowers programmed to become female, and ACS11 loss-of-function mutants lead to male plants (androecy). CmACS11 represses the expression of the male promoting gene CmWIP1 to control the development and the coexistence of male and female flowers in monoecious species. Because monoecy can lead to dioecy, we show how a combination of alleles of CmACS11 and CmWIP1 can create artificial dioecy. PMID- 26542575 TI - Improving student advising. PMID- 26542574 TI - The Symbiodinium kawagutii genome illuminates dinoflagellate gene expression and coral symbiosis. AB - Dinoflagellates are important components of marine ecosystems and essential coral symbionts, yet little is known about their genomes. We report here on the analysis of a high-quality assembly from the 1180-megabase genome of Symbiodinium kawagutii. We annotated protein-coding genes and identified Symbiodinium-specific gene families. No whole-genome duplication was observed, but instead we found active (retro)transposition and gene family expansion, especially in processes important for successful symbiosis with corals. We also documented genes potentially governing sexual reproduction and cyst formation, novel promoter elements, and a microRNA system potentially regulating gene expression in both symbiont and coral. We found biochemical complementarity between genomes of S. kawagutii and the anthozoan Acropora, indicative of host-symbiont coevolution, providing a resource for studying the molecular basis and evolution of coral symbiosis. PMID- 26542577 TI - Discovery of diffuse aurora on Mars. AB - Planetary auroras reveal the complex interplay between an atmosphere and the surrounding plasma environment. We report the discovery of low-altitude, diffuse auroras spanning much of Mars' northern hemisphere, coincident with a solar energetic particle outburst. The Imaging Ultraviolet Spectrograph, a remote sensing instrument on the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft, detected auroral emission in virtually all nightside observations for ~5 days, spanning nearly all geographic longitudes. Emission extended down to ~60 kilometer (km) altitude (1 microbar), deeper than confirmed at any other planet. Solar energetic particles were observed up to 200 kilo--electron volts; these particles are capable of penetrating down to the 60 km altitude. Given minimal magnetic fields over most of the planet, Mars is likely to exhibit auroras more globally than Earth. PMID- 26542578 TI - Dust observations at orbital altitudes surrounding Mars. AB - Dust is common close to the martian surface, but no known process can lift appreciable concentrations of particles to altitudes above ~150 kilometers. We present observations of dust at altitudes ranging from 150 to above 1000 kilometers by the Langmuir Probe and Wave instrument on the Mars Atmosphere and Volatile Evolution spacecraft. Based on its distribution, we interpret this dust to be interplanetary in origin. A comparison with laboratory measurements indicates that the dust grain size ranges from 1 to 12 micrometers, assuming a typical grain velocity of ~18 kilometers per second. These direct observations of dust entering the martian atmosphere improve our understanding of the sources, sinks, and transport of interplanetary dust throughout the inner solar system and the associated impacts on Mars's atmosphere. PMID- 26542576 TI - MAVEN observations of the response of Mars to an interplanetary coronal mass ejection. AB - Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere. PMID- 26542581 TI - Microbiomes in light of traits: A phylogenetic perspective. AB - A focus on the phenotypic characteristics of microorganisms-their traits-offers a path for interpreting the growing amount of microbiome data. We review key aspects of microbial traits, as well as approaches used to assay their phylogenetic distribution. Recent studies reveal that microbial traits are differentially conserved across the tree of life and appear to be conserved in a hierarchical fashion, possibly linked to their biochemical complexity. These results suggest a predictive framework whereby the genetic (or taxonomic) resolution of microbiome variation among samples provides information about the traits under selection. The organizational parallels seen among human and free living microbiomes seem to support this idea. Developments in this framework may offer predictions not only for how microbial composition responds to changing environmental conditions, but also for how these changes may alter the health or functioning in human, engineered, and environmental systems. PMID- 26542579 TI - Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability. AB - The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability. PMID- 26542582 TI - Controversy in myocardial regeneration. PMID- 26542580 TI - Pancreatic beta cell enhancers regulate rhythmic transcription of genes controlling insulin secretion. AB - The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior and metabolism with the solar cycle. Genetic or environmental perturbation of circadian cycles contributes to metabolic disorders including type 2 diabetes. To study the impact of the cell autonomous clock on pancreatic beta cell function, we examined pancreatic islets from mice with either intact or disrupted BMAL1 expression both throughout life and limited to adulthood. We found pronounced oscillation of insulin secretion that was synchronized with the expression of genes encoding secretory machinery and signaling factors that regulate insulin release. CLOCK/BMAL1 colocalized with the pancreatic transcription factor PDX1 within active enhancers distinct from those controlling rhythmic metabolic gene networks in liver. We also found that beta cell clock ablation in adult mice caused severe glucose intolerance. Thus, cell type-specific enhancers underlie the circadian control of peripheral metabolism throughout life and may help to explain its dysregulation in diabetes. PMID- 26542583 TI - Vale Professor Elizabeth Waters. PMID- 26542584 TI - Laparoscopy is Safe and Accurate to Evaluate Peritoneal Surface Metastasis Prior to Cytoreductive Surgery. AB - BACKGROUND: Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC. METHODS: This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected. RESULTS: A total of 145 laparoscopies were performed on 141 patients, 72 (51.1 %) of whom were female, with a median age of 53 years (range 20-79). The primary site was appendiceal in 67 (47.5 %) patients, colorectal in 43 (30.5 %), mesothelioma in 17 (12.1 %), unknown in 9 (6.4 %), small bowel in 3 (2.1 %), gastric in 1, and ovarian in 1 (0.7 % each). Overall, 115 (81.6 %) patients had prior abdominal surgery, 111 (76.6 %) had evidence of disease on imaging, and 117 (80.7 %) underwent prior chemotherapy, with a median of 5.9 weeks between the last treatment and laparoscopy (0.9-498.9 weeks). Four (2.8 %) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2 %) postoperative complications [four (2.8 %) Clavien grade (CG) I, three (2.8 %) CG II, one (0.7 %) CG III (return to operating room) and one (0.7 %) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8 %). CONCLUSION: Diagnostic laparoscopy is a safe, feasible, and accurate staging tool in patients with suspected peritoneal metastases being considered for CRS. PMID- 26542586 TI - Total Laparoscopic Central Pancreatectomy with Pancreaticogastrostomy for High Risk Cystic Neoplasm. AB - BACKGROUND: Organ-sparing pancreatic resection is important in prophylactic surgery for cystic neoplasms. There is controversy regarding the optimal surgical approach for pancreatic lesions in the neck or proximal body of the pancreas. Central compared with distal pancreatectomy is technically more challenging, but preserves more functional pancreatic tissue. Because of the prophylactic nature of the surgery and long survival of patients with benign and borderline malignant lesions, surgeons need to stratify greater importance to surgical morbidity and sparing pancreatic parenchyma. PATIENT: The patient is a 59-year-old active woman with a symptomatic cystic neoplasm of the pancreas exhibiting high-risk imaging features. The cyst of 2.2 * 1.8 cm in the body of the pancreas was impinging on the portal venous confluence. TECHNIQUE: The patient was positioned in the French Position, the lesser sac was opened, and the pancreatic body exposed. A retropancreatic tunnel was created with staple division of the neck. The body was mobilized off the portal vein and splenic vessels transected. A retrogastric pancreaticogastrostomy was sewn through an anterior gastrotomy. The stent was delivered past the pylorus to decrease pancreatic enzymatic activation. Pathology demonstrated a mixed predominantly branch duct IPMN with multifocal high grade dysplasia and PanIN3. CONCLUSIONS: Laparoscopic ultrasound helps in defining cyst borders, and minimal blood loss optimizes visualization during the dissection. A minimally invasive pancreaticogastrostomy created through an anterior gastrotomy is technically feasible and safe. This approach can minimize the morbidity of prophylactic pancreatic surgery for patients with cystic neoplasms. Nevertheless, it should not compromise safety, oncologic completeness, or an organ-sparing approach. PMID- 26542585 TI - Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020). AB - BACKGROUND: Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB. METHODS: Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations. RESULTS: A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3%; 95% confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1%; 95% CI 0.01-7) by central pathology review. CONCLUSIONS: In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3% by local pathology and 1% by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings. PMID- 26542587 TI - Double Purse-String Telescoped Pancreaticogastro stomy using an Atraumatic Self retaining Ring Retractor in a Subtotal Stomach-Preserving Pancreaticoduodenectomy. AB - BACKGROUND: Pancreatoenteric anastomotic failure is the main cause of pancreatic fistula after pancreaticoduodenectomy (PD). Double purse-string telescoped pancreaticogastrostomy, reported by Addeo et al., is an easy and safe procedure.1 The aim of this article was to introduce our technique of pancreaticogastrostomy using an atraumatic self-retaining ring retractor (Alexis Wound Retractor) in a patient undergoing subtotal stomach-preserving PD (SSPPD). PATIENT AND METHODS: An 82-year-old woman presented with pancreatic cancer located in the uncinate process of pancreas. She underwent SSPPD with resection of the superior mesenteric vein (SMV) and double purse-string telescoped pancreaticogastrostomy using an Alexis wound retractor. RESULTS: The pancreas was transected on the portal vein and the remnant pancreas was separated from the splenic vein and artery. After extirpation of specimens and reconstruction of the SMV, two seromuscular purse-string sutures were placed on the posterior wall of the upper stomach. The anterior wall of the upper stomach was incised and opened using an Alexis wound retractor. The remnant pancreas was inserted into the gastric cavity through the posterior wall of the stomach and sutured circumferentially with running stitches to fix on the gastric muco-muscular layer. After closure of the anterior wall of the stomach, purse-string sutures were tightened and pancreaticogastrostomy was completed. The patient's postoperative course was uneventful and a computed tomography imaging study revealed no fluid collection around the pancreaticogastrostomy. This patient was discharged on the 14th postoperative day. CONCLUSIONS: Use of an Alexis wound retractor makes it easier to perform a double purse-string telescoped pancreaticogastrostomy by a self expanding property to allow a wide operative view. PMID- 26542588 TI - Limited Parathyroidectomy in Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism: A Setup for Failure. AB - BACKGROUND: Recently, some surgeons have suggested that minimally invasive parathyroidectomy guided by preoperative localizing studies of patients with multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) provides an acceptable outcome while minimizing the risk of hypoparathyroidism. This study aimed to evaluate the outcome for MEN1 patients who underwent limited parathyroidectomy compared with subtotal parathyroidectomy. METHODS: The authors performed a retrospective analysis of 99 patients with MEN1 associated pHPT who underwent at least one parathyroid operation at their institution. Preoperative imaging studies, intraoperative findings, and clinical outcomes for patients were compared. RESULTS: A total of 99 patients underwent 146 operations. Persistent pHPT was significantly higher in patients whose initial operations involved removal of 1 or 2 glands (69 %) or 2.5 to 3 glands (20 %) compared with those who had 3.5 or more glands removed (6 %) (P < 0.01). Persistent pHPT occurred in 5 % of all operations that cumulatively removed 3.5 or more parathyroid glands compared with 40 % of operations that removed 3 or fewer glands (P < 0.01). The single largest parathyroid gland was correctly identified preoperatively in 69 % (22/32) of the patients. However, preoperative localizing studies missed enlarged contralateral parathyroid glands in 86 % (19/22) of these patients. Preoperative localizing studies missed the largest contralateral parathyroid gland in 16 % (5/32) of the patients. CONCLUSIONS: Limited parathyroidectomy in MEN1 is associated with a high failure rate and should not be performed. Preoperative identification of a single enlarged parathyroid gland in MEN1 is not reliable enough to justify unilateral neck exploration because additional enlarged contralateral parathyroid glands are frequently missed. PMID- 26542589 TI - Tumor Characteristics and Survival Outcome of Endometrial Cancer Arising in Adenomyosis: An Exploratory Analysis. AB - BACKGROUND: Endometrial cancer arising in adenomyosis (EC-AIA) is a rare entity of endometrial cancer, and its clinical significance has not been well studied. This study aimed to examine the tumor characteristics and survival outcomes of EC AIA. METHODS: An exploratory analysis was performed to compare EC-AIA and historical control cases. For this study, EC-AIA cases were identified via a systematic literature search using PubMed/MEDLINE with entry keywords "endometrial cancer OR uterine cancer" AND "adenomyosis" (n = 46). The control group comprised consecutive non-EC-AIA cases from four institutions that had hysterectomy-based surgical staging (n = 1294). Patient demographics, pathology results, and survival outcomes were evaluated between the two groups. RESULTS: The EC-AIA group was significantly older than the control group (58.9 vs. 55.3 years; P = 0.032). In terms of tumor characteristics, 56.5% of the EC-AIA cases showed tumor within the myometrium without endometrial extension, and the EC-AIA group was significantly more likely to have tumors with more than 50% myometrial invasion (51.6 vs. 26.6%; P = 0.002) and serous/clear cell histology (22.2 vs. 8.2%, P = 0.002) while less likely to express estrogen receptor (14.3 vs. 84.6%; P < 0.001). Grade and stage distributions were similar (P > 0.05). In the univariate analysis, the EC-AIA group had a significantly poorer disease-free survival than the control group (5-year rate: 71.4 vs. 80.6%; P = 0.014). In the multivariate analysis, with control for age, ethnicity, histology, grade, and stage, EA-CIC remained an independent prognostic factor for decreased disease free survival (adjusted hazard ratio, 3.07; 95% confidence interval 1.55-6.08; P = 0.001). CONCLUSIONS: The study suggested that endometrial cancer arising in adenomyosis may be an aggressive variant of endometrial cancer. PMID- 26542590 TI - Minimally Invasive Pancreaticoduodenectomy Does Not Improve Use or Time to Initiation of Adjuvant Chemotherapy for Patients With Pancreatic Adenocarcinoma. AB - BACKGROUND: The modifiable variable best proven to improve survival after resection of pancreatic adenocarcinoma is the addition of adjuvant chemotherapy. A theoretical advantage of minimally invasive pancreaticoduodenectomy (MI-PD) is the potential for greater use and earlier initiation of adjuvant therapy, but this benefit remains unproven. METHODS: The 2010-2012 National Cancer Data Base (NCDB) was queried for patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. Subjects were classified as MI-PD versus open pancreaticoduodenectomy (O-PD). Baseline variables were compared between groups. The independent effect of surgical approach on the use and timing of adjuvant chemotherapy was estimated using multivariable regression analyses. RESULTS: For this study, 7967 subjects were identified: 1191 MI-PD (14.9%) and 6776 O-PD (85.1%) patients. Patients who underwent MI-PD were more likely to have been treated at academic hospitals. Otherwise, the groups had no baseline differences. In both the MI-PD and O-PD groups, approximately 50% of the patients received adjuvant chemotherapy, initiated at a median of 54 versus 55 days postoperatively (p = 0.08). After multivariable adjustment, surgical approach was not independently associated with use (odds ratio 1.00; p = 0.99) or time to initiation of adjuvant chemotherapy (-2.3 days; p = 0.07). Younger age, insured status, lower comorbidity score, higher tumor stage, and the presence of lymph node metastases were independently associated with the use of adjuvant chemotherapy. CONCLUSIONS: At a national level, MI-PD does not result in greater use or earlier initiation of adjuvant chemotherapy. As surgeons and institutions continue to gain experience with this complex procedure, it will be important to revisit this benchmark as a justification for its increasing use for patients with pancreatic cancer. PMID- 26542591 TI - Avoiding Diverting Ileostomy in Patients Requiring Complete Pelvic Peritonectomy. AB - BACKGROUND: In performing cytoreductive surgery with hyperthermic perioperative chemotherapy, a rectosigmoid colon resection is frequently required. To reduce the incidence of anastomotic leakage at the colorectal anastomoses, a diverting ileostomy has been recommended in these patients. METHODS: Stripping of mesorectal fat from the rectum up to the peritoneal reflection allows transection of the rectum at the junction of the upper and middle rectum. A suture pulls in the lateral aspects of the rectal staple line so that this staple line is included within the barrel of the stapler. After the circular-stapled anastomoses is complete, a second layer of silk sutures is used to invert the staple line. RESULTS: In 31 stapled colorectal anastomoses, three rectal transections were so low that a layer of sutures was not possible. In the 29 two-layer colorectal anastomoses, no anastomotic leakages were observed. The incidence of diverting ileostomy was reduced from 50 to 7 %. CONCLUSIONS: These results suggest that preservation of a 10-15 cm length of rectum allows a second layer of sutures to be placed over the stapled colorectal anastomoses. This is a safe alternative to a diverting ileostomy in selected patients. PMID- 26542592 TI - Which Surgical Attitude to Choose in the Context of Non-Resectability of Ovarian Carcinomatosis: Beyond Gross Residual Disease Considerations. AB - BACKGROUND: In ovarian cancer, the increased rate of radical surgery comprising upper abdominal procedures has participated to improve overall survival (OS) in advanced stages by increasing the rate of complete cytoreductions. However, in the context of non-resectability, it is unclear whether radical surgery should be considered when it would lead to microscopic but visible disease (<=1 cm). We aimed to compare the survival outcomes among patients with incomplete cytoreduction according to the extent of surgery. METHODS: Overall, 148 patients presenting with advanced stage ovarian carcinomas were included in this retrospective study, regardless of treatment schedule. These patients were stratified according to the extent of surgery (standard or radical). Complete cytoreduction at the time of debulking surgery could not be carried out in all cases. RESULTS: Among our study population (n = 148), 96 patients underwent standard procedures (SPs) and 52 underwent radical surgeries (RP). Patients in the SP group had a lower Peritoneal Index Cancer (PCI) at baseline (12.6 vs. 14.9; p = 0.049). After PCI normalization, we observed similar OS in the SP and RP groups (39.7 vs. 43.1 months; p = 0.737), while patients in the SP group had a higher rate of residual disease >10 mm (p < 10(-3)). Patients in the RP group had an increased rate of relapse (p = 0.005) but no difference in disease-free survival compared with the SP group (22.2 for SP vs. 16.3 months; p = 0.333). Residual disease status did not impact survival outcomes. CONCLUSIONS: In the context of non-resectable, advanced stage ovarian cancer, standard surgery seems as beneficial as radical surgery regarding survival outcomes and should be considered to reduce surgery-associated morbidity. PMID- 26542593 TI - Noncurative Resection for Gastric Cancer Patients: Who Could Benefit? : Determining Prognostic Factors for Patient Selection. AB - BACKGROUND: Resections have long been recommended for patients with incurable gastric cancer. However, high morbidity rates and more efficient chemotherapy regimens have demanded more accurate patient selection. The aim of this study was to analyze the results of gastric cancer patients treated with noncurative resection in a single cancer center. METHODS: Medical charts of patients treated with a noncurative resection between January 1988 and December 2012 were analyzed. Individuals who had M1 disease were included, along with those with no metastasis but who had an R2 resection. Morbidity, mortality, and survival prognostic factors were analyzed. RESULTS: In the period, 192 patients were resected, 159 with previously diagnosed metastatic disease and the other 33 having resection with macroscopic residual disease (R2). A distal gastrectomy was performed in 117 patients and a total resection in 75, with a more limited lymph node dissection in 70 % of cases. A multivisceral resection was deemed necessary in 42 individuals (21.9 %). Overall morbidity was 26.6 % and 60-day mortality was 6.8 %. Splenectomy was the only independent prognostic factor for higher morbidity. Median survival was 10 months, and younger age, distal resection, and chemotherapy were independent prognostic factors for survival. A prognostic score obtained from these factors identified a 20-month median survival in patients with these favorable characteristics. CONCLUSION: Noncurative surgery may be considered in selected gastric cancer patients as long as it has low morbidity and allows the realization of chemotherapy. PMID- 26542594 TI - Association Between Preoperative Chemotherapy and Postoperative Complications in Patients Undergoing Surgery for Ovarian Cancer. AB - BACKGROUND: This study sought to determine the association between preoperative chemotherapy and postoperative morbidity and mortality in ovarian cancer patients. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was used to identify women who underwent surgery for ovarian cancer between 2005 and 2012. The women were divided into two groups based on whether they had received chemotherapy within 30 days before surgery or not. Preoperative variables, intraoperative measures, and postoperative morbidity and mortality were compared using chi(2) and Student's t test. Multivariable analyses using logistic regression modeling were used to correct for potential confounding variables. RESULTS: Of 1807 patients, 1612 (89.2%) underwent primary surgery, and 195 (10.8%) received preoperative chemotherapy. The chemotherapy group had a lower preoperative platelet count (317,640 vs 249,740 plt/MUL; P < 0.001), hematocrit (36.9 vs 33.1%; P < 0.001), and white blood cell (WBC) count (7970 vs 6060 WBC/MUL; P < 0.001). Postoperatively, the chemotherapy group had a higher rate of organ/space infection (2.2 vs 4.6%; P = 0.04; odds ratio [OR], 2.12; 95% confidence interval [CI], 1.01-4.47) and a higher blood transfusion rate (17.1 vs 32.3%; P < 0.001; OR, 2.31; 95% CI, 1.67-3.20). A subanalysis of only those with disseminated cancer showed myelosuppression and an increased blood transfusion rate in the chemotherapy group. In multivariable analyses, preoperative chemotherapy, hematocrit, and ascites were independent predictors of postoperative blood transfusion in the entire cohort, whereas preoperative chemotherapy was the only independent predictor of postoperative blood transfusion in the disseminated cancer group. CONCLUSIONS: Preoperative chemotherapy for the treatment of ovarian cancer is associated with myelosuppression and an increased risk of postoperative blood transfusion. PMID- 26542595 TI - Lund-Mackay System for Computed Tomography Evaluation of Paranasal Sinuses in Patients with Granulomatosis and Polyangiitis. AB - Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 +/- 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 +/- 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients. PMID- 26542596 TI - Oxidative Stress and Nitric Oxide in Sedentary Older Adults with Intellectual and Developmental Disabilities. AB - Individuals with moderate-to-profound intellectual and developmental disabilities (IDD) are characterized by significant cognitive deficits, abnormal muscle tone, poor posture and balance, and inactive lifestyle. Increased oxidative stress (OS) has been implicated in a variety of chronic diseases, inflammatory conditions, aging, and even following intense physical exercise. Nitric oxide (NO) is a highly reactive mediator that has been shown to play different roles in a variety of different biological process and in aging. The aim of the study was to investigate the serum levels of global OS and NO metabolites (NOx) in sedentary and non-sedentary older adults with IDD. Global OS was measured by CR 3000 instrument, FORM system, and NOx were measured by determination of serum nitrite levels. OS and NOx levels were significantly higher in sedentary IDD comparing non-sedentary controls. The increased of OS and NOx levels suggest their possible involvement in the phenomenon of 'accelerated aging' in IDD. Our findings can provide another aspect indicating both OS and NOx as possible biochemical markers and their potential application in minimizing their negative influence through future therapeutic strategies. PMID- 26542597 TI - Exacerbations of Chronic Obstructive Pulmonary Disease and Quality of Life of Patients. AB - Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the most important factors which influence the course of disease and quality of life in COPD patients. The aim of the study was to assess the exacerbation frequency in COPD patients in relation to COPD severity and to evaluate the impact of the number of exacerbations on quality of life. The study included 445 COPD patients in all four progressive stages of the disease according to GOLD classification. The patients recorded exacerbations in diaries. Spirometry, St. George's Respiratory Questionnaire, and dyspnea score were assessed at baseline and after 12 and 24 months from enrollment. After 24 months, 261 diaries were returned. The mean number of exacerbations per year in the sequential GOLD 1-4 stages of COPD was as follows: 1.3 +/- 2.1, 1.4 +/- 2.0, 1.7 +/- 1.8, and 3.4 +/- 4.5. A statistical difference in the exacerbation frequency was noted for GOLD 4 and the remaining groups. A significant negative correlation was found between the number of exacerbations and functional status for GOLD 2 and 3 stages. We conclude that the number of exacerbations is the highest in the most severe stage of the disease. The quality of life of patients with moderate and severe COPD correlates negatively with the number of exacerbations. PMID- 26542598 TI - Psychosocial Context of Differences Between Asthmatic and Diabetic Patients in Adaptation to Disease. AB - A significant rise in the incidence of asthma and diabetes makes the psychosocial underpinnings of these diseases an increasingly important issue. This article examines differences in psychosocial functioning between healthy people and patients suffering from asthma and diabetes, as separate disease entities. Psychological factors seem to play a significant role particularly in the process of recovery and adaptation to the disease. Our assumption was that a time perspective, a sense of belonging, and a hope may be related to the functioning of people with chronic asthma and diabetes. The study involved a total of 90 people assigned to three groups: healthy individuals, asthmatic patients, and diabetic patients. The findings demonstrate that patients suffering from asthma have a different attitude toward the future and a sense of fatalism in the present. Yet there are no significant differences between asthma patients and healthy individuals in the sense of belonging and hope. Diabetic patients perceive the present as more fatalistic than asthmatic patients and healthy individuals, and they are less oriented at setting and achieving future goals. The finding that the type and course of the disease are associated with specific psychosocial adaptation may have functional and therapeutic implications, and thus should get psycho-clinical attention. PMID- 26542599 TI - Breathing in Parkinsonism in the Rat. AB - Parkinsonism is underlain by dopamine (DA) deficiency in the mid-brain, a neurotransmitter innately involved with respiratory regulation. However, the state of respiration in parkinsonism is an unsettled issue. In this study we seek to determine ventilation and its responses to hypoxia in a reserpine--alpha methyl-tyrosine model of parkinsonism in the rat. We also attempted to differentiate between the role of discrete brain and carotid body DA stores in the modulation of the hypoxic ventilatory response (HVR). To this end we used domperidone, a peripheral D2 receptor antagonist, and levodopa, a central D2 receptor agonist. The HVRs to acute 12% and 8% hypoxia were studied in a whole body plethysmograph in the same rats before and after the induction of parkinsonic symptoms in conscious rats. We found that resting ventilation and the HVR were distinctly reduced in parkinsonism. The reduction was particularly evident in the peak hypoxic hyperpneic augmentation. Domperidone, which enhanced ventilation in the control healthy condition, failed to reverse the reduced parkinsonic HVR. In contrast, levodopa, which did not appreciably affected ventilation in the healthy condition, caused the parkinsonic HVR to return to and above the baseline healthy level. The findings demonstrate the predominance of a lack of the central DA stimulatory element and minimize the role of carotid body DA in the ventilatory impediment of parkinsonism. In conclusion, the study provides the pathophysiological savvy concerning the respiratory insufficiency of parkinsonism, a sequela which carries a risk of chronically impaired blood oxygenation, which may drive the disease worsening. PMID- 26542600 TI - Thyroid Hormone Levels and TSH Activity in Patients with Obstructive Sleep Apnea Syndrome. AB - Obstructive sleep apnea syndrome (OSAS) is characterized by complete cessation of inspiratory flow (apnea) or upper airway airflow limitation (hypopnea) with increased respiratory muscle activity, which is repeatedly observed during sleep. Hypothyroidism has been described as a rare cause of OSAS, but it is considered to be the main cause of breathing disorders during sleep in patients in whom an improvement of OSAS is observed after thyroid hormone replacement therapy. Nevertheless, euthyreosis due to thyroxine replacement in patients with OSAS often does not improve the breathing disorder and treatment with continuous positive airway pressure is usually applied. The aim of this study was to assess thyroid function in patients with OSAS. We studied 813 patients in whom severe OSAS was diagnosed; the mean apnea-hypopnea index was 44.0. Most of the patients were obese (mean BMI 33.1 +/- 6.6 kg/m2) and had excessive daytime sleepiness (ESS 12.8 +/- 6.6). With the thyroid stimulating hormone (TSH) concentration as the major criterion, hypothyroidism was diagnosed in 38 (4.7%) and hyperthyroidism was diagnosed in 31 (3.8%) patients. Analysis of basic anthropometric data, selected polysomnography results, and TSH, fT3, and fT4 values did not reveal any significant correlations. In conclusion, the incidence of thyroid function disorders seems to be no different in OSAS than that in the general population. We did not find correlations between TSH activity and the severity of breathing disorders during sleep. PMID- 26542601 TI - The Influence of Shockwave Therapy on Orthodontic Tooth Movement Induced in the Rat. AB - Shockwave therapy is used in medicine due to its ability to stimulate healing processes. The application of orthodontic force evokes an inflammatory reaction resulting in tooth movement. Shockwave therapy might have an effect on both inflammatory and periodonal ligament cytokine profiles. Our aim was to evaluate the fluctuations of different inflammatory cytokines after orthodontic force induction with and without shockwave therapy. An orthodontic appliance was applied between the rats' molars and incisors. In conjunction with the commencement of orthodontic force, the rats were treated with a single episode of 1000 shock waves and the gingival crevicular fluid was collected for 3 days. The expression and concentration of different cytokines was evaluated by a commercial 4-multiplex fluorescent bead-based immunoassay. The level of all cytokines displayed a similar trend in both shockwave-treated and untreated groups; the concentration peaked on the first day and declined thereafter. In all cases, however, the cytokine levels were smaller in the shockwave-treated than in untreated animals; a significant difference was found for sRANKL and borderline difference for IL-6 on Day 1. We conclude that shockwave therapy during the induction of orthodontic tooth movement influences the expression of inflammatory cytokines. PMID- 26542602 TI - The Role of Human Herpesvirus 8 in Diabetes Mellitus Type 2: State of the Art and a Medical Hypothesis. AB - Diabetes is a common chronic disease due to an altered glucose metabolism, caused by the quantitative and/or qualitative dysfunction of the insulin hormone. Two types of diabetes are recognized: juvenile diabetes, or type 1, which has an autoimmune origin, and adult diabetes, or type 2 (DMT2), which covers 90-95 % of all diabetic patients.The causes of DMT2 are not yet clear: heredity, life style, nutrition, and environment are considered the main risk factors. Several viral infections, namely cytomegalovirus, coxsackie and other enteroviruses, rubella and hepatitis C virus, have been claimed to be associated with some forms of diabetes. The direct role of viruses as a cause or as a risk of type 1 diabetes has been amply described in several recent reviews. Therefore, this review focuses attention on the role of a human herpes pathogenic virus in the onset of DMT2. By carrying out an analysis of recent literature, we describe the findings reported on an extremely deceitful virus, such as Human Herpes virus 8, and present a medical hypothesis on a possible relationship between this virus and DMT2. PMID- 26542603 TI - Antioxidant Hydroxytyrosol-Based Polyacrylate with Antimicrobial and Antiadhesive Activity Versus Staphylococcus Epidermidis. AB - The accumulation of reactive oxygen species (ROS) in microbial biofilms has been recently recognized to play a role in promoting antibiotic resistance in biofilm growing bacteria. ROS are also over-produced when a medical device is implanted and they can promote device susceptibility to infection or aseptic loosening. High levels of ROS seem also to be responsible for the establishment of chronic wounds.In this study, a novel antioxidant polyacrylate was synthesized and investigated in terms of antimicrobial and antibiofilm activity. The polymer possesses in side-chain hydroxytyrosol (HTy), that is a polyphenolic compound extracted from olive oil wastewaters.The obtained 60 nm in size polymer nanoparticles showed good scavenging and antibacterial activity versus a strain of Staphylococcus epidermidis. Microbial adherence assays evidenced that the hydroxytyrosol-containing polymer was able to significantly reduce bacterial adhesion compared to the control. These findings open novel perspective for a successful use of this antioxidant polymer for the prevention or treatment of biofilm-based infections as those related to medical devices or chronic wounds. PMID- 26542604 TI - Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes and Alcoholic Ketosis Are Associated with the Serum Uric Acid Level in Japanese Alcoholic Men. AB - AIMS: To identify determinants of hyperuricemia in alcoholics. METHODS: The serum uric acid (UA) levels of 1759 Japanese alcoholic men (>=40 years) were measured on their first visit or within 3 days after admission; ADH1B and ALDH2 genotyping on blood DNA samples were performed. Dipstick urinalyses for ketonuria and serum UA measurements were simultaneously performed for 621 men on their first visit. RESULTS: Serum UA levels of >416 MUmol/l (7.0 mg/dl) and >=535 MUmol/l (9.0 mg/dl) were observed in 30.4 and 7.8% of the subjects, respectively. Ketonuria was positive in 35.9% of the subjects, and a multivariate analysis revealed that the ketosis level was positively associated with the UA level. The presence of the ADH1B*2 allele and the ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) among subjects with a high UA level of >416 MUmol/l (vs. <=416 MUmol/l; 2.04 [1.58-2.65] and 1.48 [1.09-2.01], respectively) and those with a high UA level of >=535 MUmol/l (vs. <=416 MUmol/l; 2.29 [1.42-3.71] and 3.03 [1.51-6.08], respectively). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs (2.86 [1.61-5.10] and 6.21 [1.49-25.88] for a UA level of >416 MUmol/l and >=535 MUmol/l, respectively), compared with the ADH1B*1/*1 plus ALDH2*1/*2 combination. The presence of diabetes and the consumption of Japanese sake rather than beer were negatively associated with the UA levels. CONCLUSIONS: The faster metabolism of ethanol and acetaldehyde by the ADH1B*2 allele and ALDH2*1/*1 genotype and higher ketosis levels were associated with higher UA levels in alcoholics, while diabetes and the consumption of sake were negative determinants. PMID- 26542605 TI - The Particular Story of Italians' Relation with Alcohol: Trends in Individuals' Consumption by Age and Beverage Type. AB - AIMS: In Italy, sales data show a dramatic fall in alcohol consumption between 1970 and 2010. The aim of our study is to provide updated information on trends, prevalence and determinants of alcohol drinking in Italy, using individual-level data. METHODS: Seven nationally representative cross-sectional surveys were conducted in Italy between 2006 and 2014, on a total sample of 21,416 participants aged >=15 years, with available information on weekly consumption of wine, beer and spirits. RESULTS: Per capita alcohol consumption decreased by 23% between 2006 and 2014 (from 5.6 to 4.4 drinks/week), due to the fall in wine drinking. Overall, the prevalence of alcohol drinkers was 61.6%. Individuals predominantly drinking wine were 35.3%, beer 11.1% and spirits 6.4%. A direct trend of drinking with age was observed for total alcohol (multivariate odds ratio, OR = 1.75 for >=65 vs. 15-24 years) and predominant wine drinking (OR = 8.05), while an inverse trend was observed for beer (OR = 0.17) and spirit drinkers (OR = 0.33). Women (OR = 0.24), obese individuals (OR = 0.67) and those from southern Italy (OR = 0.63) were less frequently, while those with high education (OR = 1.97), ex- (OR = 1.46) and current smokers (OR = 2.17) were more frequently alcohol drinkers. CONCLUSION: On the basis of individual-level data we confirm and further update to 2014 the decreasing trend in alcohol consumption in Italy over the last few decades, mainly due to the fall in wine consumption. This may be due to anti-alcohol policies, programs and campaigns adopted and developed over the last decade. It also reflects socio-cultural changes in drinking, particularly in younger generations. PMID- 26542606 TI - Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6 hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells. AB - There is increasing evidence that free radicals induced oxidative stress is a major causative agent in the pathogenesis of neurodegenerative diseases, particularly Parkinson's disease. Quercetin glycosides, namely rutin and isoquercitrin, are flavonoid polyphenol compounds found ubiquitously in fruits and vegetables and have been known to possess antioxidant effects. This study was designed to compare the neuroprotective effects of quercetin glycosides rutin and isoquercitrin in 6-OHDA-induced rat pheochromocytoma (PC-12) cells. The results showed that both rutin and isoquercitrin significantly increased antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and glutathione level that were attenuated by 6-OHDA in PC-12 cells. There was no significant difference in the activation of glutathione and glutathione peroxidase enzymes between rutin and isoquercitrin. These two glycosides were equally effective in suppressing lipid peroxidation in 6-OHDA-induced PC-12 cells as both compounds suppressed the malondialdehyde generation and prevented cell damage. In conclusion, quercetin glycosides rutin and isoquercetrin are having a significant neuroprotective effect against 6-OHDA toxicity in PC-12 cells. PMID- 26542607 TI - Thromboprophylaxis after caesarean: when even the 'experts' disagree. PMID- 26542608 TI - Predictors of depressive symptoms in older Japanese primiparas at 1 month post partum: A risk-stratified analysis. AB - AIM: Older maternal age has become more common in Japan. Studies suggest that older maternal age and primiparity are associated with post-partum depression. The present study aimed to identify predictors of post-partum depression in older Japanese primiparas at 1 month post-partum. METHODS: Participants were 479 primiparas aged 35 years and over, drawn from a prospective cohort study. Data were collected using self-report questionnaires. Depression was measured with the Japanese version of the Edinburgh Postnatal Depression Scale. Stepwise logistic regression analysis was conducted on binary outcome variables of depression at 1 month post-partum, along with a stratified analysis based on the risk status of depression. RESULTS: Five predictors were identified: (i) the depression score during hospital stay; (ii) financial burden; (iii) dissatisfaction with appraisal support; (iv) physical burden in daily life; and (v) concerns about infant caretaking. Stratified analysis identified dissatisfaction with instrumental support in the low-risk group, and the Child-care Value Scale score as unique predictors in the high-risk group. CONCLUSION: These results highlight the importance of early assessment of depressive symptoms and the provision of continuous care. PMID- 26542609 TI - Immunohistochemical characterization of appendiceal mucinous neoplasms and the value of special AT-rich sequence-binding protein 2 in their distinction from primary ovarian mucinous tumours. AB - AIMS: The distinction between primary ovarian mucinous tumours and appendiceal mucinous neoplasms metastatic to the ovary can be challenging, given the overlap of morphological features and immunohistochemical expression of traditional markers. Special AT-rich sequence-binding protein 2 (SATB2) has recently been described as a sensitive and specific marker of colorectal epithelium. This study was to determine its expression in appendiceal mucinous tumours and its role in their distinction from ovarian neoplasms. METHODS AND RESULTS: Immunohistochemistry was performed in tissue microarrays from 32 primary appendiceal mucinous tumours (25 low-grade appendiceal mucinous neoplasms and seven adenocarcinomas) and 40 ovarian mucinous neoplasms (20 borderline tumours and 20 adenocarcinomas). Stains were interpreted as positive or negative by scoring intensity and distribution. SATB2 was positive in 93.8% of appendiceal tumours and in only one ovarian tumour; SATB2 was 97.5% specific for appendiceal origin. CK20, CDX2 and MUC2 were strongly and diffusely positive in appendiceal tumours; ovarian tumours were also positive, but with a patchy distribution and mild intensity. CK7 was expressed in 97.5% of ovarian tumours and in 31.2% of appendiceal tumours. PAX8 was positive in 70% of ovarian tumours, and negative in all appendiceal lesions. CONCLUSIONS: SATB2 is frequently expressed in appendiceal mucinous neoplasms. In the context of a mucinous neoplasm involving the ovary, any SATB2 positivity should raise the possibility of appendiceal origin. Expression of CK20, CDX2 and MUC2 supports appendiceal origin only when diffuse and strong. These and other markers, such as CK7 and PAX8, are recommended in the work-up of ovarian mucinous tumours with any clinical or pathological features suggestive of secondary origin. PMID- 26542610 TI - Foreword. PMID- 26542611 TI - Pump Thrombosis: A Limitation of Contemporary Left Ventricular Assist Devices. AB - For the majority of patients with heart failure (HF) the management is non surgical, but for the most advanced subgroup of patients with heart failure and reduced ejection fraction, mechanical circulatory support (MCS) is becoming a more viable treatment option. Heart transplantation is the 'gold standard' for advanced HF therapy, but is limited by donor organ availability. In contrast, MCS utilization has risen exponentially over the past decade. Pump thrombosis is a rare but increasingly recognized cause of morbidity and mortality in this population. In this review, we define the problem of pump thrombosis, discuss diagnostic testing and approaches to the prevention and management of this potentially devastating complication of durable MCS. PMID- 26542612 TI - Pregnancy diabetes: A comparison of diagnostic protocols based on point-of-care, routine and optimized laboratory conditions. AB - In vitro glycolysis poses a problem during diabetes screening, especially in remote laboratories. Point-of-care analysis (POC) may provide an alternative. We compared POC, routine and STAT analysis and a feasible protocol during glucose tolerance test (GTT) for pregnancy diabetes (GDM) screening. In the routine protocol, heparin tubes were used and turn-around-time (TAT) was unsupervised. In the STAT protocol, tubes were processed immediately. The feasible protocol comprised of citrated tubes with a TAT of 1 hour. Outcome was defined as glucose concentration and clinical diagnosis. Glucose measured by POC was higher compared to routine analysis at t = 0 (0.25 mM) and t = 120 (1.17 mM) resulting in 17% more GDM diagnoses. Compared to STAT analysis, POC glucose was also higher, although less pronounced (0.06 and 0.9 mM at t = 0 and t = 120 minutes, respectively) and misclassification was only 2%. Glucose levels and clinical diagnosis were similar using the feasible protocol and STAT analysis (0.03 mM and -0.07 mM at t = 0 and t = 120, 100% identical diagnoses). POC is an viable alternative for STAT glucose analysis in GDM screening (sensitivity: 100%, specificity: 98%). A feasible protocol (citrated phlebotomy tubes with a TAT of 60 minutes) resulted in 100% identical outcome and provides the best alternative. PMID- 26542613 TI - Pattern Recognition in Pharmacodynamic Data Analysis. AB - Pattern recognition is a key element in pharmacodynamic analyses as a first step to identify drug action and selection of a pharmacodynamic model. The essence of this process is going from data to insight through exploratory data analysis. There are few formal strategies that scientists typically use when the experiment has been done and data collected. This report attempts to ameliorate this deficit by identifying the properties of a pharmacodynamic model via dissection of the pattern revealed in response-time data. Pattern recognition in pharmacodynamic analyses contrasts with pharmacokinetic analyses with respect to time course. Thus, the time course of drug in plasma usually differs markedly from the time course of the biomarker response, as a consequence of a myriad of interactions (transport to biophase, binding to target, activation of target and downstream mediators, physiological response, cascade and amplification of biosignals, homeostatic feedback) between the events of exposure to test compound and the occurrence of the biomarker response. Homing in on this important-but less often addressed-element, 20 datasets of varying complexity were analyzed, and from this, we summarize a set of points to consider, specifically addressing baseline behavior, number of phases in the response-time course, time delays between concentration- and response-time courses, peak shifts in response with increasing doses, saturation, and other potential nonlinearities. These strategies will hopefully give a better understanding of the complete pharmacodynamic response time profile. PMID- 26542614 TI - Impulsivity in body-focused repetitive behavior disorders: Disparate clinical associations between three distinct measures. AB - OBJECTIVE: Research on trichotillomania (TTM) and excoriation (skin-picking) disorder (SPD) has suggested that impulsivity may be an important cognitive underpinning of the behavior, but many studies have produced mixed results. This analysis assessed impulsivity in TTM and SPD using three measures: the Barratt Impulsiveness Scale (BIS), the Eysenck Impulsiveness Questionnaire (EIQ), and the Stop-Signal Task (SST). METHODS: Two hundred and eighty three subjects with TTM or SPD completed measurement of impulsivity as a part of participation in several research studies. Subjects scoring one standard deviation above or below measure means were included in the analysis for that scale (SST: N = 45; EIQ: N = 32; BIS: N = 34). High and low impulsive groups were compared within measures on demographic, clinical, and behavioral variables. RESULTS: Results differed by group, with domains of the BIS showing associations with clinical severity, quality of life, and anxiety, and the SST showing several differences, but not clinical severity. The EIQ domains showed no significant differences. No groups differed demographically. CONCLUSIONS: These results suggest that the EIQ, BIS, and SST assess distinct characteristics. Notably, only the attentional domain from the BIS predicted higher severity scores. Future research needs to clarify the ideal utility for these scales as they relate to TTM and SPD. Key points The BIS, EIQ, and SST domains are associated with distinct clinical differences between high and low impulsivity groups. Only the subjects in the high attentional impulsivity domain of the BIS showed significantly elevated symptom severity. The high and low impulsivity groups within the EIQ domains did not show any significant differences. These disparate associations may indicate the need for better subtyping of impulsivity, as different measures of specific domains appear to show associations with distinct features. PMID- 26542615 TI - Further exploring the absorption and enterocyte metabolism of quercetin forms in the Caco-2 model using nano-LC-TOF-MS. AB - When using the Caco-2 intestinal model, the low uptake, intracellular presence at low levels as well as generation of trace metabolites may limit the analysis of flavonoids. To overcome these limitations, we performed a simple but sensitive methodology based on nano-LC-TOF-MS, using an on-line trapping step. The analytical method was validated for quercetin, quercetin 3-O-glucoside, and quercetin 3-O-glucuronide and the reliability for characterization using lock mass calibration was also assessed along the linear range. Afterwards, the in vitro absorption, metabolism, and cellular occurrence were explored with the proposed methodology. The apparent permeability coefficient in the absorptive direction and the cellular accumulation were higher for quercetin aglycone, with a value of 2.61 * 10(-6) cm/s and relative amounts of 0.73 and 1.17% in the cytosolic and solid particle fraction at the end of the assay, respectively. Alternatively, the net efflux ratio was lower for quercetin than for their derivatives. Moreover, depending on the structure of the parent compound, metabolites were generated by glucuronidation, sulfation, and methylation. PMID- 26542616 TI - Participatory action research in corrections: The HITEC 2 program. AB - BACKGROUND: HITEC 2 (Health Improvement through Employee Control 2) is the follow up to HITEC, a participatory action research (PAR) program that integrates health and work conditions interventions designed by the workforce. HITEC 2 compares intervention programs between two correctional sites, one using a pure workforce level design team and the other using a more structured and time delineated labor management kaizen effectiveness team. METHODS: HITEC 2 utilizes a seven step participatory Intervention Design and Analysis Scorecard (IDEAS) for planning interventions. Consistent with PAR, process and intervention efficacy measures are developed and administered through workforce representation. RESULTS: Participation levels, robustness of participatory structures and sophistication of interventions have increased at each measured interval. Health comparisons between 2008 and 2013 showed increased hypertension, static weight maintenance, and increased 'readiness to change'. CONCLUSIONS: The PAR approaches are robust and sustained. Their long-term effectiveness in this population is not yet clear. PMID- 26542617 TI - Dependent personality, separation anxiety disorder and other anxiety disorders in OCD. AB - BACKGROUND: The purpose of this study was to investigate whether dependent personality and/or general personality dimensions might explain the strong relationships between separation anxiety disorder (Sep-AD) and three other anxiety disorders (agoraphobia, panic disorder and social anxiety disorder) in individuals with obsessive compulsive disorder (OCD). METHODS: Using data from 509 adult participants collected during the OCD Collaborative Genetic Study, we used logistic regression models to evaluate the relationships between Sep-AD, dependent personality score, general personality dimensions and three additional anxiety disorders. RESULTS: The dependent personality score was strongly associated with Sep-AD and the other anxiety disorders in models adjusted for age at interview, age at onset of OC symptoms and worst ever OCD severity score. Several general personality dimensions, especially neuroticism, extraversion and conscientiousness, were also related to Sep-AD and the other anxiety disorders. Sep-AD was not independently related to these anxiety disorders, in multivariate models including general personality and dependent personality disorder scores. CONCLUSIONS: The results suggest that Sep-AD in childhood and these other anxiety disorders in adulthood are consequences of dependent personality disorder (for agoraphobia and panic disorder) or introversion (for social phobia). It is unknown whether these results would be similar in a non-OCD sample. PMID- 26542618 TI - Right frontal pole cortical thickness and executive functioning in children with traumatic brain injury: the impact on social problems. AB - Cognitive and social outcomes may be negatively affected in children with a history of traumatic brain injury (TBI). We hypothesized that executive function would mediate the association between right frontal pole cortical thickness and problematic social behaviors. Child participants with a history of TBI were recruited from inpatient admissions for long-term follow-up (n = 23; average age = 12.8, average time post-injury =3.2 years). Three measures of executive function, the Trail Making Test, verbal fluency test, and the Conners' Continuous Performance Test-Second edition (CPT-II), were administered to each participant while caregivers completed the Childhood Behavior Checklist (CBCL). All participants underwent brain magnetic resonance imaging following cognitive testing. Regression analysis demonstrated right frontal pole cortical thickness significantly predicted social problems. Measures of executive functioning also significantly predicted social problems; however, the mediation model testing whether executive function mediated the relationship between cortical thickness and social problems was not statistically significant. Right frontal pole cortical thickness and omission errors on the CPT-II predicted Social Problems on the CBCL. Results did not indicate that the association between cortical thickness and social problems was mediated by executive function. PMID- 26542619 TI - White matter integrity in polydrug users in relation to attachment and personality: a controlled diffusion tensor imaging study. AB - The relationship between substance use disorders (SUD) and brain deficits has been studied extensively. However, there is still a lack of research focusing on the structural neural connectivity in long-term polydrug use disorder (PUD). Since a deficiency in white matter integrity has been reported as being related to various parameters of increased psychopathology, it might be considered an aggravating factor in the treatment of SUD. In this study we compared two groups of PUD inpatients (abstinent: n = 18, in maintenance treatment: n = 15) to healthy controls (n = 16) with respect to neural connectivity in white matter, and their relation to behavioral parameters of personality factors/organization and attachment styles. Diffusion Tensor Imaging was used to investigate white matter structure. Compared with healthy controls, the PUD patients showed reduced fractional anisotropy (FA) and increased radial diffusivity (RD) mainly in the superior fasciculus longitudinalis and the superior corona radiata. These findings suggest diminished neural connectivity as a result of myelin pathology in PUD patients. In line with our assumptions, we observed FA in the biggest cluster as negatively correlated with anxious attachment (r = 0.36, p < 0.05), personality dysfunctioning (r = -0.41; p < 0.01) as well positively correlated with personality factors Openness (r = 0.34; p < 0.05) and Agreeableness (r = 0.28; p < 0.05). Correspondingly these findings were inversely mirrored by RD. Further research employing enhanced samples and addressing longitudinally neuronal plastic effects of SUD treatment in relation to changes in personality and attachment is recommended. PMID- 26542620 TI - Neurophysiological correlates of persistent psycho-affective alterations in athletes with a history of concussion. AB - Understanding the neuropathological underpinnings of sport-related concussion are critical for diagnosis, prognosis, and remediation. Although electro encephalographic (EEG) methods have proven invaluable for understanding psycho affective pathologies in various clinical conditions, they have not been used to understand the psycho-affective outcomes of concussive injuries. Accordingly, we evaluated the relation of electroencephalographic (EEG) power in collegiate athletes to psycho-affective measures. We predicted that athletes with a history of concussion would exhibit alterations in frontal EEG asymmetries indicative of increased depression, anxiety and more general mood disturbance. During this cross-sectional study, resting EEG and measures of mood and affect, including the Beck Depression Inventory-II (BDI-II) and Profile of Mood States (POMS) were collected in 81 young-adult male athletes (52 concussion history; 29 controls). All athletes with a history of concussion (9+ months from injury) reported to be symptom free, and all participants were actively taking part in their sport at the time of testing. Compared to control athletes, the athletes with a history of concussion exhibited alterations in frontal-alpha and frontal-beta asymmetry (p's < .05). Correlational analyses revealed that alterations in frontal-alpha asymmetry were related to self-reported depression and anxiety, and alterations in beta-asymmetry were related to self-reported anger/aggression, but these relations were only significant for athletes with a history of concussion. The current study suggests that athletes with a history of concussion who made a complete return to play and reported to be asymptomatic on a commonly used symptom checklist may still exhibit neural activity associated with increased levels of depression, anxiety and anger/hostility. The current results reinforce the clinical necessity for long-term evaluations of athletes irrespective of apparent symptom resolution, and suggest that EEG may serve as a sensitive tool to identify and track concussion-related alterations in psycho-affective health before they manifest as clinical disorders. PMID- 26542621 TI - Aged care nurse practitioners working in general practice. PMID- 26542622 TI - Melioidosis in New Caledonia: a dominant strain in a transmission hotspot. AB - Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases and B. pseudomallei isolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group of B. pseudomallei that is phylogenetically related to Australian strains. PMID- 26542624 TI - Atrial myocytes demonstrate the diversity of cardiac calcium signalling. PMID- 26542625 TI - Degrading vision with too much Ca(2+). PMID- 26542626 TI - Piece treaties connect ENaC subunits. PMID- 26542627 TI - TRPM3 joins the ranks of PI(4,5)P2 sensitive ion channels. PMID- 26542629 TI - Corrigendum. PMID- 26542628 TI - Anticonvulsant mechanisms of piperine, a piperidine alkaloid. AB - Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na(+) and Ca(2+) channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na(+) channels. Together, our data suggest Na(+) channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine. PMID- 26542630 TI - Synthesis of magnetic cobalt ferrite nanoparticles with controlled morphology, monodispersity and composition: the influence of solvent, surfactant, reductant and synthetic conditions. AB - In our present work, magnetic cobalt ferrite (CoFe2O4) nanoparticles have been successfully synthesised by thermal decomposition of Fe(III) and Co(II) acetylacetonate compounds in organic solvents in the presence of oleic acid (OA)/ oleylamine (OLA) as surfactants and 1,2-hexadecanediol (HDD) or octadecanol (OCD ol) as an accelerating agent. As a result, CoFe2O4 nanoparticles of different shapes were tightly controlled in size (range of 4-30 nm) and monodispersity (standard deviation only at ca. 5%). Experimental parameters, such as reaction time, temperature, surfactant concentration, solvent, precursor ratio, and accelerating agent, in particular, the role of HDD, OCD-ol, and OA/OLA have been intensively investigated in detail to discover the best conditions for the synthesis of the above magnetic nanoparticles. The obtained nanoparticles have been successfully applied for producing oriented carbon nanotubes (CNTs), and they have potential to be used in biomedical applications. PMID- 26542631 TI - Increased expressions of ADAMTS-13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice. AB - Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS-13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS-13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl-xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post-infection. Results of the study revealed that the levels of ADAMTS-13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl-xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post-infection ADAMTS-13 increased significantly and this may play an important role in the regulation and protection of the blood-brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii-mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS-13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of T. gondii-infected mice. PMID- 26542632 TI - Simple HPLC-UV for the quantification of a new leishmanicidal candidate (E)-1 4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine (LASSBio 1736) in rat plasma for pharmacokinetics assessment. AB - In this study, a sensitive HPLC-UV assay was developed and validated for the determination of LASSBio-1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid-liquid extraction using acetonitrile was employed to extract LASSBio-1736 and IS from 100 MUL of plasma previously basified with NaOH 0.1 M. Chromatographic separation was carried on Waters Spherisorb((r)) S5 ODS2 C18 column (150 * 4.6 mm, 5 MUm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pH 4), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1 mL/min. Both LASSBio-1736 and IS were eluted at 4.2 and 5 min, respectively, with a total run time of 8 min only. The lower limit of quantification was 0.2 MUg/mL and linearity between 0.2 and 4 MUg/mL was obtained, with an R(2) > 0.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio-1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26542633 TI - Comparative plasma pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in neonatal calves. AB - The objective of this study was to compare the plasma pharmacokinetic profile of ceftiofur crystalline-free acid (CCFA) and ceftiofur sodium in neonatal calves between 4 and 6 days of age. In one group (n = 7), a single dose of CCFA was administered subcutaneously (SQ) at the base of the ear at a dose of 6.6 mg/kg of body weight. In a second group (n = 7), a single dose of ceftiofur sodium was administered SQ in the neck at a dose of 2.2 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) in plasma were determined by HPLC. Median time to maximum DCA concentration was 12 h (range 12-48 h) for CCFA and 1 h (range 1-2 h) for ceftiofur sodium. Median maximum plasma DCA concentration was significantly higher for calves given ceftiofur sodium (5.62 MUg/mL; range 4.10 6.91 MUg/mL) than for calves given CCFA (3.23 MUg/mL; range 2.15-4.13 MUg/mL). AUC0-infinity and Vd/F were significantly greater for calves given CCFA than for calves given ceftiofur sodium. The median terminal half-life of DCA in plasma was significantly longer for calves given CCFA (60.6 h; range 43.5-83.4 h) than for calves given ceftiofur sodium (18.1 h; range 16.7-39.7 h). Cl/F was not significantly different between groups. The duration of time median plasma DCA concentrations remained above 2.0 MUg/mL was significantly longer in calves that received CCFA (84.6 h; range 48-103 h) as compared to calves that received ceftiofur sodium (21.7 h; range 12.6-33.6 h). Based on the results of this study, CCFA administered SQ at a dose of 6.6 mg/kg in neonatal calves provided plasma concentrations above the therapeutic target of 2 MUg/mL for at least 3 days following a single dose. It is important to note that the use of ceftiofur containing products is restricted by the FDA and the use of CCFA in veal calves is strictly prohibited. PMID- 26542634 TI - Tumour immunology: Reducing silence to improve therapy. PMID- 26542635 TI - Immunotherapy: Remote control CARs. PMID- 26542637 TI - An in vitro attenuated strain of Histomonas meleagridis provides cross-protective immunity in turkeys against heterologous virulent isolates. AB - In the current study, cross-protective immunity induced by a well-defined clonal strain of Histomonas meleagridis, attenuated by prolonged in vitro cultivation against different clonal heterologous isolates of the same parasite was investigated. For this purpose, 86 turkey poults were assigned to groups consisting of 9-10 birds. Birds of four groups were vaccinated on their 1st day of life followed by re-vaccination on their 14th day of life when the remaining turkeys were left untreated. The challenge was performed using four strains of H. meleagridis that were isolated from chickens or turkeys from different outbreaks of histomonosis in Europe and three of them showed diversities in their genome. Hence, every strain used for the challenge was applied to a group of vaccinated and a group of non-vaccinated birds while birds of the negative control group were sham inoculated. Non-vaccinated birds suffered from severe histomonosis due to the challenge with fatalities reaching from 5 to 10 turkeys per group. Vaccinated birds did not contract clinical signs of the disease following challenge and the increase in weight was unaffected compared to birds of the negative control group. A significant difference in lesion scores was recorded between vaccinated and non-vaccinated groups, with very few instances of liver involvement in the former groups. Livers of vaccinated birds that were without recordable macroscopic lesions were also found negative by immunohistochemical investigation. According to the data obtained, the present study demonstrates, for the first time, the cross-protective capability of a tentative vaccine strain of H. meleagridis attenuated in vitro against heterologous virulent isolates of different origin. PMID- 26542636 TI - Combination of acamprosate and baclofen as a promising therapeutic approach for Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopaminergic nigrostriatal neurons but which involves the loss of additional neurotransmitter pathways. Mono- or polytherapeutic interventions in PD patients have declining efficacy long-term and no influence on disease progression. The systematic analysis of available genetic and functional data as well as the substantial overlap between Alzheimer's disease (AD) and PD features led us to repurpose and explore the effectiveness of a combination therapy (ABC) with two drugs - acamprosate and baclofen - that was already effective in AD animal models, for the treatment of PD. We showed in vitro that ABC strongly and synergistically protected neuronal cells from oxidative stress in the oxygen and glucose deprivation model, as well as dopaminergic neurons from cell death in the 6-hydroxydopamine (6-OHDA) rat model. Furthermore, we showed that ABC normalised altered motor symptoms in vivo in 6-OHDA-treated rats, acting by protecting dopaminergic cell bodies and their striatal terminals. Interestingly, ABC also restored a normal behaviour pattern in lesioned rats suggesting a symptomatic effect, and did not negatively interact with L-dopa. Our results demonstrate the potential value of combining repurposed drugs as a promising new strategy to treat this debilitating disease. PMID- 26542638 TI - Pharmacological research and precision cancer medicine: A call for manuscripts. PMID- 26542639 TI - Values, inter-attitudinal structure, and attitude change: value accessibility can increase a related attitude's resistance to change. AB - Accessibility is one of the most basic structural properties of an attitude and an important factor to consider in attitude strength. Despite its importance, relatively little work has examined the role of attitude accessibility in an inter-attitudinal context, particularly as it relates to the strength of related attitudes in the network. The present research examines accessibility as a property of one attitude (toward an abstract goal or end-state, that is, a value) that might influence the strength of a different but related attitude (toward a social policy conceptually related to the value). In Study 1, a highly accessible evaluative component of a value increased resistance to change of attitudes and behavioral intentions toward a social policy related to that value. Similarly, a manipulation of value accessibility (Studies 2 and 3) led to increased resistance of attitudes and behavioral intentions toward a social policy related to that value. Implications for the role of accessibility in inter-attitudinal strength are discussed. PMID- 26542640 TI - Ultrafast Laser Studies of Two-Photon Excited Fluorescence Intermittency in Single CdSe/ZnS Quantum Dots. AB - Two-photon fluorescence microscopy of single quantum dots conditions has been reported by several groups, with contrasting observations regarding the kinetics and dynamics of fluorescence intermittency or "blinking". Here, we investigate the power dependence, kinetics, and statistics of two photon-excited fluorescence intermittency from single CdSe/ZnS quantum dots in a solid PMMA film as a function of sub-bandgap laser intensity at 800 nm. Fluorescence intermittency is observed at all excitation powers and a quadratic (n = 1.97(3)) dependence of the shot noise-limited fluorescence intensity on the incident laser power is verified, confirming essentially zero background contribution from one-photon excitation processes. Such analyses permit two photon absorption cross sections for single quantum dots to be extracted quantitatively from the data, which reveal good agreement with those obtained from previous two-photon FCS measurements. Strictly inverse power law-distributed off-state dwell times are observed for all excitation powers, with a mean power law exponent ?m(off)? = 1.65(4) in excellent agreement with the behavior observed under one-photon excitation conditions. Finally, a superquadratic (n = 2.3(2)) rather than quartic (n = 4) power dependence is observed for the on-state blinking dwell times, which we kinetically analyze and interpret in terms of a novel 2 + 1 "hot" exciton ionization/blinking mechanism due to partially saturated 1-photon sub-bandgap excitation out of the two-photon single exciton state. The kinetic results are consistent with quantum dot photoionization quantum yields from "hot" exciton states (4(1) * 10(-6)) comparable with experimental estimates (10(-6)-10(-5)) of Auger ionization efficiencies out of the biexcitonic state. PMID- 26542641 TI - Two-State or Non-Two-State? An Excess Spectroscopy-based Approach to Differentiate the Existing Forms of Molecules in Liquids Mixtures. AB - Characterization/identification of the clusters/associates in liquids has long been a challenging topic. In this paper, we report a method to identify molecules with two different existing forms in a binary liquid solution. In this so-called two-state situation, the excess infrared spectra of a vibration mode of the respective molecule will show identical band shape if the other component is transparent in the region. More conveniently, the positions of the positive peak, negative peak, and zero-value will be seen to be fixed with varying compositions of the binary system. In the case of non-two-state mixtures, for example the mere solvation of solute by solvent, those positions will be variable. The conclusions are supported/demonstrated by computational simulation and experiments on two binary systems, D2O-H2O and C6F5I-cyclo-C6H12. PMID- 26542642 TI - Fracture Risk Is Decreased in Women With Polycystic Ovary Syndrome: A Register Based and Population-Based Cohort Study. AB - Hyperandrogenism, obesity, and hyperinsulinemia may protect against osteoporosis, whereas amenorrhea, increased cortisol, and low growth hormone may be associated with higher fracture risk in polycystic ovary syndrome (PCOS). The objective of this study was to investigate fracture risk in PCOS. In the PCOS Denmark study, women with PCOS and/or hirsutism were identified in the Danish National Patient Register (1995-2012). Each patient was assigned three age-matched controls on the index date of PCOS diagnosis. Individuals with a previous endocrine diagnosis were excluded. Within PCOS Denmark, we embedded a well-characterized subcohort of patients, PCOS OUH, diagnosed with PCOS at Odense University Hospital (n = 1217). We identified incident fractures by International Classification of Diseases, 10th Revision (ICD-10) codes and used conditional Cox regression analyses to compare fracture risk. In the PCOS Denmark study, there were 19,199 women with PCOS and 57,483 controls were included, mean age 30.6 years (range, 12-60 years). Fracture rates were decreased in PCOS Denmark (10.3/1000 patient years) versus controls (13.6/1000 patient years). The adjusted ORs were 0.76 (95% CI, 0.71 to 0.80) for all fractures, 0.82 (95% CI, 0.74 to 0.92) for major osteoporotic fractures, and 0.57 (95% CI, 0.47 to 0.70) for fractures of head and face. The risk reduction was more pronounced below the age of 30 years at diagnosis. Women with PCOS had significant more hospital contacts due to strains and sprains. In the PCOS OUH subcohort, the risk reduction of fractures did not differ between PCOS women with elevated versus normal testosterone levels and the risk reduction was nominally smaller in overweight versus normal weight PCOS women. Women with PCOS had reduced risk of fractures, in particular of the appendicular skeleton. The risk reduction was greater in women with younger age at diagnosis suggesting that the skeletal effects of PCOS may be greater in women who have not yet reached peak bone mass. Reduced participation in sports activities was probably not the reason for the reduced risk of fractures. PMID- 26542643 TI - Commentary on "Tracking of radiation exposure in pediatric stone patients: The time is now". PMID- 26542644 TI - Shouldn't the laparoscopic operation for inguinal hernia repair in children be some steps closer to the open procedure? PMID- 26542645 TI - Cyanide Single-Molecule Magnets Exhibiting Solvent Dependent Reversible "On" and "Off" Exchange Bias Behavior. AB - The syntheses, structures, and magnetic properties of four new complex salts, (PPN){[Mn(III)(salphen)(MeOH)]2[M(III)(CN)6]}.7MeOH (Mn2M.7MeOH) (M = Fe, Ru, Os and Co; PPN(+) = bis(triphenylphosphoranylidene)ammonium cation; H2salphen = N,N' bis(salicylidene)-1,2-diaminobenzene), and a mixed metal Co/Os analogue (PPN){[Mn(III)(salphen)(MeOH)]2[Co(III)0.92Os(III)0.08(CN)6]}.7MeOH were undertaken. It was found that all compounds exhibit switchable single-molecule magnet (SMM) and exchange-bias behavior depending on the interstitial methanol content. The pristine (PPN){[Mn(salphen)(MeOH)]2[Os(CN)6]}.7MeOH (Mn2Os.7MeOH) behaves as an SMM with an effective barrier for the magnetization reversal, (Ueff/kB), of 17.1 K. Upon desolvation, Mn2Os exhibits an increase of Ueff/kB to 42.0 K and an opening of the hysteresis loop observable at 1.8 K. Mn2Os.7MeOH shows also exchange-bias behavior with magnetic hysteresis loops exhibiting a shift in the quantum tunneling to 0.25 T from zero-field. The Fe(III) and Ru(III) analogues were prepared as reference compounds for assessing the effect of the 5d versus 4d and 3d metal ions on the SMM properties. These compounds are also SMMs and exhibit similar effects but with lower energy barriers. These findings underscore the importance of introducing heavy transition elements into SMMs to improve their slow relaxation of the magnetization properties. The (PPN){[Mn(III)(salphen)(MeOH)]2[Co(III)(CN)6]}.7MeOH (Mn2Co.7MeOH) analogue with a diamagnetic Co(III) central atom and the mixed Co/Os (PPN){[Mn(III)(salphen)(MeOH)]2[Co(III)0.92Os(III)0.08(CN)6]}.7MeOH (Mn2Co/Os.7MeOH) "magnetically diluted" system with a 9:1 Co/Os metal ratio were prepared in order to further probe the nature of the energy barrier increase upon desolvation of Mn2Os. In addition, inelastic neutron scattering and frequency domain Fourier-transform THz electron paramagnetic resonance spectra obtained on Mn2Os.7MeOH and Mn2Os in combination with the magnetic data revealed the presence of anisotropic exchange interactions between Mn(III) and Os(III) ions. PMID- 26542647 TI - Inhibition of dengue virus production and cytokine/chemokine expression by ribavirin and compound A. AB - Dengue virus (DENV) infection is a worldwide public health problem with an increasing magnitude. The severity of disease in the patients with DENV infection correlates with high viral load and massive cytokine production - the condition referred to as "cytokine storm". Thus, concurrent inhibition of DENV and cytokine production should be more effective for treatment of DENV infection. In this study, we investigated the effects of the antiviral agent - ribavirin (RV), and the anti-inflammatory compound - compound A (CpdA), individually or in combination, on DENV production and cytokine/chemokine transcription in human lung epithelial carcinoma (A549) cells infected with DENV. Initially, the cells infected with DENV serotype 2 (DENV2) was studied. The results showed that treatment of DENV-infected cells with RV could significantly reduce both DENV production and cytokine (IL-6 and TNF-alpha) and chemokine (IP-10 and RANTES) transcription while treatment of DENV-infected cells with CpdA could significantly reduce cytokine (IL-6 and TNF-alpha) and chemokine (RANTES) transcription. Combined RV and CpdA treatment of the infected cells showed greater reduction of DENV production and cytokine/chemokine transcription. Similar results of this combined treatment were observed for infection with any one of the four DENV (DENV1, 2, 3, and 4) serotypes. These results indicate that combination of the antiviral agent and the anti-inflammatory compound offers a greater efficiency in reduction of DENV and cytokine/chemokine production, providing a new therapeutic approach for DENV infection. PMID- 26542648 TI - Cationic amphiphilic drugs enhance entry of lentiviral particles pseudotyped with rabies virus glycoprotein into non-neuronal cells. AB - Amiodarone and other cationic amphiphilic drugs (CADs) inhibit cell entry by diverse human pathogenic viruses including Filoviruses, Dengue virus and Japanese encephalitis virus. They are thus considered potential broad spectrum antiviral agents. Here we report the unexpected finding that amiodarone and other CADs markedly enhance rabies virus (RABV) glycoprotein- (GP-) mediated cell entry of pseudotyped lentiviruses into non-neuronal cells but not in neuronal cells. Increased cell entry can also be elicited when CADs are added several hours after pseudoviral attachment. Perturbing endosomal processing with phosphoinosite-3 kinase inhibitors wortmannin and LY294002 mimics the effects of CADs on RABV GP mediated cell entry. Thus, CADs may enhance RABV GP-mediated cell entry of pseudotyped lentiviruses by promoting a late step of the pseudoviral cell entry process, possibly release from an endosomal compartment into the cytosol. In contrast to the pseudotyped lentiviruses, infection by fully infectious RABV was not enhanced by CADs, indicating, that the observed stimulation of RABV GP mediated lentivirus entry also depended on the used lentivirus vector backbone. In conclusion, we show that while CADs inhibit cell entry of diverse viruses they can also have a paradoxical enhancing effect on the ability of a viral glycoprotein to mediate cell entry depending on the cellular and viral context. Although, we show CAD-mediated enhancement of entry only for pseudoviruses, but not fully infectious RABV, the potential to unexpectedly enhance viral entry should be taken into account when considering use of CADs as antiviral agents. PMID- 26542649 TI - Clinical characteristics in adult patients with Salmonella bacteremia and analysis of ciprofloxacin-nonsusceptible isolates. AB - BACKGROUND/PURPOSE: The purpose of this study is to describe clinical characteristics of Salmonella bacteremia in adult patients and analyze ciprofloxacin-nonsusceptible isolates. METHODS: A total of 101 Salmonella blood isolates from adult patients were collected from January 2011 to December 2013 in MacKay Memorial Hospital. Eight ciprofloxacin-nonsusceptible Salmonella blood isolates were screened for carbapenemase and other beta lactamase genes. Isolates were examined by PCR for the quinolone resistance-determining region (QRDR) of all subunits for DNA gyrase (gyrA and gyrB) genes and topoisomerase IV (parC and parE) genes. RESULTS: There were 22 (21.78%) S. enterica serovar B, 5 (4.95%) S. enterica serovar C1, 7 (6.93%) S. enterica serovar C2, 65 (64.36%) S. enterica serovar D, and 2 (1.98%) S. enterica serovar Typhi (S. typhi) isolates. beta lactamase gene screening and sequencing yielded only one blaCMY-2-positive isolate. In multivariate risk factor analysis, renal insufficiency [odds ratio (OR) 3.774; p = 0.020] and heart disease (OR 2.922; p = 0.027) were more common among elderly patients (>=65 years). Independent risk factors for ciprofloxacin nonsusceptible strains included S. enterica serovar C2 (OR 28.430; p = 0.032), renal insufficiency (OR 13.927; p = 0.032), and immunosuppression agent usage (OR 60.082; p = 0.006). 87.50% (7/8) of isolates had gyrA mutation, 62.50% (5/8) had parC mutation, and none had gyrB and parE mutations. Isolates with both Ser83Phe/Asp87Asn gyrA and Thr57Ser/Ser80Ile parC mutation genes were highly ciprofloxacin-resistant (minimum inhibitory concentration >=4 mg/L). CONCLUSIONS: Elderly patients with renal insufficiency and heart disease were at risk for Salmonella bacteremia. Those for ciprofloxacin-nonsusceptible strains included S. enterica serovar C2, renal insufficiency, and immunosuppression agent usage. The 8 ciprofloxacin-nonsusceptible isolates carried gyrA and parC mutations, which cause resistance that poses a major concern. PMID- 26542650 TI - Effects of corticosteroid and neuraminidase inhibitors on survival in patients with respiratory distress induced by influenza virus. AB - BACKGROUND/PURPOSE: Neuraminidase inhibitors (NAIs) including oseltamivir and peramivir are used for influenza treatment. A systemic corticosteroid is usually administrated for acute respiratory distress syndrome. The aim of this study was to investigate the effect of a systemic corticosteroid and its interaction with NAIs in patients with influenza infection and respiratory distress. METHODS: A retrospective survey of hospitalized patients infected with influenza from January 2012 to May 2014 was conducted in a medical center in Taiwan. RESULTS: Eighty-six patients were hospitalized during the study period. Forty-eight patients had respiratory distress and 39 of them (81.3%, 39/48) were supported by a mechanical ventilator. All patients with respiratory distress received oseltamivir; 60.4% (29/48) and 31.3% (15/48) of them received a corticosteroid and salvage intravenous peramivir, respectively. All-cause mortality was 29.1% (14/48), 20% (3/15), and 31% (9/29) in patients with respiratory distress, patients who received salvage peramivir, and patients who received a systemic corticosteroid, respectively. Salvage peramivir seemed to improve prognosis in patients with H1pdm09 or type B virus infection and respiratory distress (p = 0.05). Early initiating corticosteroid had a worse prognosis than initiation after 72 hours of NAI treatment (p = 0.024). In particular, a systemic corticosteroid seemed to lead to a shorter survival time in patients with chronic lung disease (p = 0.05). CONCLUSION: Salvage peramivir provided a better prognosis than monotherapy with oseltamivir in patients who were infected with H1pdm09 or type B virus and who developed respiratory distress. A systemic corticosteroid should be administered after initiating NAI therapy, especially in patients with chronic lung disease. PMID- 26542651 TI - A comparison of the management of venous leg ulceration by specialist and generalist community nurses: A judgement analysis. AB - BACKGROUND: Venous leg ulcer management in the UK varies significantly. Judgements made by nurses contribute to this variability and it is often assumed that specialist nurses make better judgements than non-specialist nurses. This paper compares the judgements of community tissue viability specialist nurses and community generalist nurses; specifically, the ways they use clinical information and their levels of accuracy. OBJECTIVES: To compare specialist and non specialist UK community nurses' clinical information use when managing venous leg ulceration and their levels of accuracy when making diagnoses and judging the need for treatment. DESIGN: Judgement analysis. SETTING: UK community and primary care nursing services. PARTICIPANTS: 18 community generalist nurses working in district (home) nursing teams and general practitioner services and 18 community tissue viability specialist nurses. METHODS: Data were collected in 2011 and 2012. 18 community generalist nurses and 18 community tissue viability specialist nurses made diagnostic and treatment judgements on 110 clinical scenarios and indicated their confidence in each of their judgements. Scenarios were generated from real patient cases and presented online using text and photographs. An expert panel made judgements, and reached consensus on the same scenarios. These judgements were used as a standard against which to compare the participants. Logistic regression models and correlational statistics were used to generate various indices of judgement "performance": accuracy, consistency, confidence calibration and information use. Differences between groups of nurses with different levels of characteristics linked to expertise were explored using analysis of variance. RESULTS: Specialist nurses had similar cue usage to the generalist nurses but were more accurate when making diagnostic and treatment judgements. CONCLUSION: It is not obvious why the tissue viability specialist nurses were more accurate. One possible reason might be the greater opportunities for 'deliberate practice' afforded to specialists. However, restricting aspects of practice only to specialist nurses is likely to hinder the judgement performance of generalists. PMID- 26542652 TI - A systematic review of the effectiveness and roles of advanced practice nursing in older people. AB - OBJECTIVES: To identify, assess and summarize available scientific evidence about the effect of interventions deployed by advanced practice nurses when providing care to older people in different care settings, and to describe the roles and components of the interventions developed by these professionals. BACKGROUND: In older people, evidence of advanced practice roles remains dispersed along different contexts, approaches and settings; there is little synthesis of evidence, and it is not easy to visualize the different practice models, their components, and their impact. DESIGN: Systematic review. DATA SOURCES: Sixteen electronic databases were consulted (1990-2014). The research also included screening of original studies in reviews and reports from Centers of Health Services Research and Health Technology Agencies. REVIEW METHODS: Studies were assessed by two reviewers with the Cochrane risk of bias tool. They were classified depending on the type of follow-up (long and short-term care) and the scope of the service (advanced practice nurses interventions focused on multimorbid patients, or focused on a specific disease). RESULTS: Fifteen studies were included. In long-term settings, integrative, multi-component and continuous advanced practice nursing care, reduced readmissions, and increased patients' and caregivers' satisfaction. Advanced practice nurses were integrated within multidisciplinary teams and the main interventions deployed were patient education, multidimensional assessments and coordination of multiple providers. CONCLUSION: Positive results have been found in older people in long-term care settings, although it is difficult to discern the specific effect attributable to them because they are inserted in multidisciplinary teams. Further investigations are needed to evaluate the cost-effectiveness of the two modalities detected and to compare internationally the interventions developed by advanced practice nurses. PMID- 26542653 TI - [Gender perspective in socio-health care needs]. AB - Social conditions are the first environment that modulate external factors which impact on health. In turn gender is a decisive factor in these social determinants of health. This paper analyzes gender bias in the health system as a relevant part in social determinants. We can distinguish three types of bias: cognitive, social, and institutional. In the institutional biases, we analyze the risks of gender and costs originated from the coordination between the health system and the system of social protection. Finally, we suggest a series of measures to minimize these biases and risks. PMID- 26542654 TI - Physical fatigue increases neural activation during eyes-closed state: a magnetoencephalography study. AB - BACKGROUND: Fatigue, defined as difficulty initiating or sustaining voluntary activities, can be classified as physical or mental. In this study, we use magnetoencephalography (MEG) to quantify the effect of physical fatigue on neural activity under the condition of simulated physical load. METHODS: Thirteen healthy right-handed male volunteers participated in this study. The experiment consisted of one fatigue-inducing physical task session performed between two MEG sessions. During the 10-min physical task session, participants performed maximum effort handgrips with the left hand lasting 1 s every 4 s; during MEG sessions, 3 min recordings were made during the eyes-closed state. MEG data were analyzed using narrow-band adaptive spatial filtering methods. RESULTS: Alpha-frequency band (8-13 Hz) power in the left postcentral gyrus, precentral gyrus, and middle frontal gyrus (Brodmann's areas 1, 2, 3, 4, 6, and 46) were decreased after performing the physical fatigue-inducing task. CONCLUSIONS: These results show that performing the physical fatigue-inducing task caused activation of the left sensorimotor and prefrontal areas, manifested as decreased alpha-frequency band power in these brain areas. Our results increase understanding of the neural mechanisms of physical fatigue. PMID- 26542655 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542656 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 1: Classification of Sports: Dynamic, Static, and Impact: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542657 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542658 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 6: Hypertension: A Scientific Statement from the American Heart Association and the American College of Cardiology. PMID- 26542659 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542660 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 4: Congenital Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542661 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 11: Drugs and Performance-Enhancing Substances: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542662 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 10: The Cardiac Channelopathies: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542663 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 15: Legal Aspects of Medical Eligibility and Disqualification Recommendations: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542664 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542665 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 12: Emergency Action Plans, Resuscitation, Cardiopulmonary Resuscitation, and Automated External Defibrillators: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542666 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 8: Coronary Artery Disease: A Scientific Statement from the American Heart Association and American College of Cardiology. PMID- 26542667 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 5: Valvular Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542668 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 14: Sickle Cell Trait: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542669 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 13: Commotio Cordis: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542670 TI - Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 9: Arrhythmias and Conduction Defects: A Scientific Statement From the American Heart Association and American College of Cardiology. PMID- 26542671 TI - Effect of antiresorptive and anabolic bone therapy on development of osteoarthritis in a posttraumatic rat model of OA. AB - INTRODUCTION: Osteoarthritis (OA) is a leading cause of disability, but despite the high unmet clinical need and extensive research seeking dependable therapeutic interventions, no proven disease-modifying treatment for OA is currently available. Due to the close interaction and interplay between the articular cartilage and the subchondral bone plate, it has been hypothesized that antiresorptive drugs can also reduce cartilage degradation, inhibit excessive turnover of the subchondral bone plate, prevent osteophyte formation, and/or that bone anabolic drugs might also stimulate cartilage synthesis by chondrocytes and preserve cartilage integrity. The benefit of intensive zoledronate (Zol) and parathyroid hormone (PTH) therapy for bone and cartilage metabolism was evaluated in a rat model of OA. METHODS: Medial meniscectomy (MM) was used to induce OA in male Lewis rats. Therapy with Zol and human PTH was initiated immediately after surgery. A dynamic weight-bearing (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs. At the end of the 10-week study, the rats were euthanized and the cartilage pathology was evaluated by contrast (Hexabrix)-enhanced MUCT imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization. RESULTS: The results of this study highlight the complex changes in bone metabolism in different bone compartments influenced by local factors, including inflammation, pain and mechanical loads. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by contrast-enhanced MUCT and histology. The study results showed the negative impact of MM surgery on the weight-bearing capacity of the operated limb, which was not corrected by treatment. Although both Zol and PTH improved subchondral bone mass and Zol reduced serum CTX-II level, both treatments failed to prevent or correct cartilage deterioration, osteophyte formation and mechanical incapacity. CONCLUSIONS: The various methods utilized in this study showed that aggressive treatment with Zol and PTH did not have the capacity to prevent or correct the deterioration of the hyaline cartilage, thickening of the subchondral bone plate, osteophyte formation or the mechanical incapacity of the osteoarthritic knee. PMID- 26542672 TI - Malaria, anaemia and under-nutrition: three frequently co-existing conditions among preschool children in rural Rwanda. AB - BACKGROUND: Malaria, anaemia and under-nutrition are three highly prevalent and frequently co-existing diseases that cause significant morbidity and mortality particularly among children aged less than 5 years. Currently, there is paucity of conclusive studies on the burden of and associations between malaria, anaemia and under-nutrition in Rwanda and comparable sub-Saharan and thus, this study measured the prevalence of malaria parasitaemia, anaemia and under-nutrition among preschool age children in a rural Rwandan setting and evaluated for interactions between and risk determinants for these three conditions. METHODS: A cross-sectional household (HH) survey involving children aged 6-59 months was conducted. Data on malaria parasitaemia, haemoglobin densities, anthropometry, demographics, socioeconomic status (SES) and malaria prevention knowledge and practices were collected. RESULTS: The prevalences of malaria parasitaemia and anaemia were 5.9 and 7.0 %, respectively, whilst the prevalence of stunting was 41.3 %. Malaria parasitaemia risk differed by age groups with odds ratio (OR) = 2.53; P = 0.04 for age group 24-35 months, OR = 3.5; P = 0.037 for age group 36 47 months, and OR = 3.03; P = 0.014 for age group 48-60 months, whilst a reduced risk was found among children living in high SES HHs (OR = 0.37; P = 0.029). Risk of anaemia was high among children aged >=12 months, those with malaria parasitaemia (OR = 3.86; P <= 0.0001) and children living in HHs of lower SES. Overall, under-nutrition was not associated with malaria parasitaemia. Underweight was higher among males (OR = 1.444; P = 0.019) and children with anaemia (OR = 1.98; P = 0.004). CONCLUSIONS: In this study group, four in 10 and one in 10 children were found stunted and underweight, respectively, in an area of low malaria transmission. Under-nutrition was not associated with malaria risk. While the high prevalence of stunting requires urgent response, reductions in malaria parasitaemia and anaemia rates may require, in addition to scaled-up use of insecticide-treated bed nets and indoor residual insecticide spraying, improvements in HH SES and better housing to reduce risk of malaria. PMID- 26542673 TI - The association between physical activity and sexual dysfunction in patients with diabetes mellitus of European and South Asian origin: The Oxford Sexual Dysfunction Study. AB - BACKGROUND: The present study aims to evaluate the relationship between physical activity and sexual dysfunction amongst an ethnic South Asian population living in the United Kingdom and compare the association with that of the native Caucasian population. METHODS: Twenty-five general practitioner clinics from eight primary care trusts in the United Kingdom collaborated in the Oxford Sexual Dysfunction Study. In each practice, a sample of diabetic and non-diabetic patients of European/Europid and South Asian origin were invited for the study. Erectile dysfunction (ED) was assessed using a five-item version of the International Index of Erectile Function. Premature ejaculation (PE) was diagnosed using the premature ejaculation diagnostic tool. Libido was assessed by asking participants to grade their desire for sexual activity. Physical activity during the past week was assessed using the short version of the International Physical Activity Questionnaire (IPAQ). A binary logistic regression analysis was performed in all adults, Europids and South Asians with 'presence of ED' as the dichotomous dependent variable (0 = ED absent; 1 = ED present) and age, diabetes status, physical activity, ethnicity, current smoking and use of antihypertensive medications as the independent variables. RESULTS: Sample size was 510, and mean age was 56.9 +/- 9.7 years. There were 63.9 % (n = 326) Europid males in the study population. The prevalence of ED was 64.5 % and it was significantly higher in men with diabetes than in those without diabetes (84.4 vs. 49.0 %, p < 0.001). The overall prevalence of PE was 28.8 %, (with diabetes 32.6 %, without diabetes 25.8 %; p = 0.109). Reduced libido was reported by 26.9 % of study participants (with diabetes 32.8 %, without diabetes 22.0 %; p < 0.01). The median (IQR) total physical activity of the study population was 2373 (3612) MET-min/week. In the IPAQ categorical score, 36.8 % (n = 184/434) males were 'highly active', and 17.8 % (n = 89/434) were 'inactive'. In all adults, age (OR: 1.06), South Asian ethnicity (OR: 1.40), physical inactivity (OR: 1.62) and presence of diabetes (OR: 3.90) all were associated with significantly increased risk of developing ED. A similar result was observed in Europids but not in South Asians. CONCLUSIONS: Erectile dysfunction was associated with physical inactivity, mainly in Europid males, irrespective of diabetes status. This association was not observed in South Asian males with or without diabetes. PMID- 26542674 TI - Interpreting digit ratio (2D:4D)-behavior correlations: 2D:4D sex difference, stability, and behavioral correlates and their replicability in young children. AB - The popularity of using the ratio of the second to the fourth digit (2D:4D) to study influences of early androgen exposure on human behavior relies, in part, on a report that the ratio is sex-dimorphic and stable from age 2 years (Manning etal., 1998). However, subsequent research has rarely replicated this finding. Moreover, although 2D:4D has been correlated with many behaviors, these correlations are often inconsistent. Young children's 2D:4D-behavior correlations may be more consistent than those of older individuals, because young children have experienced fewer postnatal influences. To evaluate the usefulness of 2D:4D as a biomarker of prenatal androgen exposure in studies of 2D:4D-behavior correlations, we assessed its sex difference, temporal stability, and behavioral correlates over a 6- to 8-month period in 126, 2- to 3-year-old children, providing a rare same-sample replicability test. We found a moderate sex difference on both hands and high temporal stability. However, between-sex overlap and within-sex variability were also large. Only 3 of 24 correlations with sex-typed behaviors-scores on the Preschool Activities Inventory (PSAI), preference for a boy-typical toy, preference for a girl-typical toy, were significant and in the predicted direction, all of which involved the PSAI, partially confirming findings from another study. Correlation coefficients were larger for behaviors that showed larger sex differences. But, as in older samples, the overall pattern showed inconsistency across time, sex, and hand. Therefore, although sex-dimorphic and stable, 2D:4D-behavior correlations are no more consistent for young children than for older samples. Theoretical and methodological implications are discussed. PMID- 26542675 TI - Correction: Probing viscoelastic response of soft material surfaces at the nanoscale. PMID- 26542676 TI - What should we do to optimise outcome in twin pregnancy complicated with placenta percreta? A case report. AB - BACKGROUND: Patients with morbidly adherent placenta (MAP) are under risk of massive bleeding. It readily necessitates very complicated surgery and massive blood transfusion, and even leads to mortality. Cesarean hysterectomy (CH) is the procedure that is acknowledged worldwide, since it helps to minimize complications. CASE PRESENTATION: A patient with dichorionic twin pregnancy underwent to cesarean section (CS) due to preliminary diagnosis of placenta percreta at her 35(th) week of pregnancy. Both of the placentas were left in situ. The patient admitted with signs of infection. Emergency total abdominal hysterectomy was performed 7 weeks after CS. In the course of hysterectomy, 3 units of erythrocyte suspension and 2 units of fresh frozen plasma were transferred, whereas none was required during CS. CONCLUSION: Abandoning placenta in situ seems to be a logical alternative to the CH in patients with placenta percreta in order to minimize complications related to massive blood transfusion and surgical technique. However, it appears to increase maternal morbidity due to maternal infection in twin pregnancy. PMID- 26542677 TI - Refractive errors and refractive development in premature infants. AB - PURPOSE: To examine refractive errors and refractive development in premature infants. METHODS: Premature infants in the retinopathy of prematurity (ROP) screening program were recruited and examined longitudinally between 28 and 58 weeks postmenstrual age. For performing cycloplegic retinoscopy, 1% tropicamide was administered, two drops with a 10-minute interval, in order to paralyze accommodation and to achieve cycloplegia. Birth weight, gestational age, gender and acute ROP disease were recorded. The relationship between spherical equivalent, astigmatism and postmenstrual age was evaluated. RESULTS: A total of 798 readings were obtained from 258 infants (131 females, 127 males) between 28 and 58 weeks postmenstrual age. The median number of examinations was 3 (minimum 1, maximum 7). In the comparisons of birth weight, gestational age, spherical equivalent and astigmatism between genders, there were no statistically significant differences (P>0.05). Gestational age (regression analysis, r(2)=0.30, P<0.01) and birth weight (regression analysis, r(2)=0.22, P<0.01) had a significant effect on refractive error development. Preterm babies with lower birth weight and those born more prematurely had lower spherical equivalent. The spherical equivalent of the eyes correlated significantly with the postmenstrual age of the infants (r=0.512, P<0.01). CONCLUSIONS: Infants with low gestational age and low birth weight also had low spherical equivalent. Moreover, spherical equivalent correlated with increasing postmenstrual age. However, astigmatism did not correlate with postmenstrual age and did not associate with gestational age or birth weight. PMID- 26542678 TI - [Role of surgery in the management of pigmented iris tumors: Case report]. PMID- 26542679 TI - [Assessment of postoperative pain after corneal collagen cross-linking by iontophoresis vs the rapid epithelium-off technique in progressive keratoconus patients]. AB - INTRODUCTION: Cross-linking (CXL) increases corneal biomechanical strength in progressive keratoconus. Since riboflavin cannot penetrate intact corneal epithelium, removal of epithelium is necessary for the classic CXL procedure (epi off), but can cause severe postoperative pain. To avoid this problem, a method preserving the epithelium (epi-on) is used. In this study, we aimed to evaluate and compare postoperative pain after epi-off CXL and epi-on CXL. MATERIALS AND METHODS: We present a retrospective study assessing the level of pain postoperatively in 38 patients between the age of 12 and 53 years who underwent CXL procedures at the University Hospital of Clermont-Ferrand from July 2013 to May 2014. Epi-off consisted of manual corneal de-epithelialization and riboflavin instillation for 20minutes, followed by UVA exposure for 9minutes. The epi-on technique used an applicator on the eye, filled with riboflavin, and a generator delivered a continuous low-level current for 5minutes. The duration of light exposure was similar in both groups. Postoperative medications were the same for both techniques. Assessment of pain and analgesic intake were reported by the patient on paper questionnaires. Pain was evaluated from preoperatively up until the end of the month. Statistical analyses were performed in bilateral formulation to an alpha type I and error risk of 5%. RESULTS: Twenty-three epi off patients and 15 epi-on patients. Twenty-nine men and 9 women (76.3%/23.7%). Mean age: 28 years. Reference base time was the return from the operating room. In the epi-off group, pain increased significantly until the morning of D2 and did not return to its intraoperative level until noon D2, 1.8+/-2.0 vs 2.5+/-2.5 (P=0.12). Pain remained stable until the morning of D4. From noon D4 until D30, it was significantly less than intraoperatively 1.8+/-2.0 vs 0.7+/-1.4 (P=0.01). In the epi-on group, pain was significantly higher than intraoperatively until noon of D1 2.5+/-2.2 vs 3.8+/-2.5 (P=0.01). From the evening of D1, it returned to its intraoperative level until the evening of D2 2.5+/-2.2 vs 2+/-1.7 (P=0.34). From the morning of D3 it was significantly less than intraoperatively 2.5+/-2.2 vs 0.8+/-0.9 (P=0.001). Considering all measurement times, there was no significant difference between the two groups (P=0.75), except from evening of D2 until evening of D3 in favor of iontophoresis: 1.9+/-2.3 vs 1.0+/-1.3 (P=0.038). DISCUSSION: Epi-on seems less painful in the short term (up to noon of D1 for epi on vs morning of D2 for epi-off) and with a shorter duration than epi-off. This can be explained by the absence of corneal de-epithelialization. However, the reduction in pain is not significant at all postoperative times, and a risk of epithelial abrasion during placement and removal of the corneal applicator may exist. CONCLUSION: Iontophoresis maintains the corneal epithelium, decreases pain and improves patient comfort. A new study involving more patients and strict monitoring of medication intake would strengthen the validity of these results. PMID- 26542680 TI - Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules. AB - Microtubules (MTs) are hollow cytoskeletal filaments assembled from alphabeta tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer's. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; PhiTau = 1/10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to PB ~ 10,000-20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (PB ~ 1,000-2,000 Pa) over the same range. Remarkably, the abrupt increase in PB observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < PhiTau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT-MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment. PMID- 26542681 TI - Screening for tumor suppressors: Loss of ephrin receptor A2 cooperates with oncogenic KRas in promoting lung adenocarcinoma. AB - Lung adenocarcinoma, a major form of non-small cell lung cancer, is the leading cause of cancer deaths. The Cancer Genome Atlas analysis of lung adenocarcinoma has identified a large number of previously unknown copy number alterations and mutations, requiring experimental validation before use in therapeutics. Here, we describe an shRNA-mediated high-throughput approach to test a set of genes for their ability to function as tumor suppressors in the background of mutant KRas and WT Tp53. We identified several candidate genes from tumors originated from lentiviral delivery of shRNAs along with Cre recombinase into lungs of Loxp-stop Loxp-KRas mice. Ephrin receptorA2 (EphA2) is among the top candidate genes and was reconfirmed by two distinct shRNAs. By generating knockdown, inducible knockdown and knockout cell lines for loss of EphA2, we showed that negating its expression activates a transcriptional program for cell proliferation. Loss of EPHA2 releases feedback inhibition of KRAS, resulting in activation of ERK1/2 MAP kinase signaling, leading to enhanced cell proliferation. Intriguingly, loss of EPHA2 induces activation of GLI1 transcription factor and hedgehog signaling that further contributes to cell proliferation. Small molecules targeting MEK1/2 and Smoothened hamper proliferation in EphA2-deficient cells. Additionally, in EphA2 WT cells, activation of EPHA2 by its ligand, EFNA1, affects KRAS-RAF interaction, leading to inhibition of the RAS-RAF-MEK-ERK pathway and cell proliferation. Together, our studies have identified that (i) EphA2 acts as a KRas cooperative tumor suppressor by in vivo screen and (ii) reactivation of the EphA2 signal may serve as a potential therapeutic for KRas-induced human lung cancers. PMID- 26542682 TI - The ever-emerging complexity of alpha-toxin's interaction with host cells. PMID- 26542683 TI - Atmospheric Ar and Ne returned from mantle depths to the Earth's surface by forearc recycling. AB - In subduction zones, sediments, hydrothermally altered lithosphere, fluids, and atmospheric gases are transported into the mantle, where ultrahigh-pressure (UHP) metamorphism takes place. However, the extent to which atmospheric noble gases are trapped in minerals crystallized during UHP metamorphism is unknown. We measured Ar and Ne trapped in phengite and omphacite from the youngest known UHP terrane on Earth to determine the composition of Ar and Ne returned from mantle depths to the surface by forearc recycling. An (40)Ar/(39)Ar age [7.93 +/- 0.10 My (1sigma)] for phengite is interpreted as the timing of crystallization at mantle depths and indicates that (40)Ar/(39)Ar phengite ages reliably record the timing of UHP metamorphism. Both phengite and omphacite yielded atmospheric (38)Ar/(36)Ar and (20)Ne/(22)Ne. Our study provides the first documentation, to our knowledge, of entrapment of atmospheric Ar and Ne in phengite and omphacite. Results indicate that a subduction barrier for atmospheric-derived noble gases does not exist at mantle depths associated with UHP metamorphism. We show that the crystallization age together with the isotopic composition of nonradiogenic noble gases trapped in minerals formed during subsolidus crystallization at mantle depths can be used to unambiguously assess forearc recycling of atmospheric noble gases. The flux of atmospheric noble gas entering the deep Earth through subduction and returning to the surface cannot be fully realized until the abundances of atmospheric noble gases trapped in exhumed UHP rocks are known. PMID- 26542684 TI - Short-term outcome and differences between rural and urban trauma patients treated by mobile intensive care units in Northern Finland: a retrospective analysis. AB - BACKGROUND: Emergency medical services are an important part of trauma care, but data comparing urban and rural areas is needed. We compared 30-day mortality and length of intensive care unit (ICU) stay for trauma patients injured in rural and urban municipalities and collected basic data on trauma care in Northern Finland. METHODS: We examined data from all trauma patients treated by the Finnish Helicopter Emergency Medical Services in 2012 and 2013. Only patients surviving to hospital were included in the analysis but all pre-hospital deaths were recorded. All data was retrieved from the national Helicopter Emergency Medical Services database, medical records, and the Finnish Causes of Death Registry. Patients were defined as urban or rural depending on the type of municipality where the injury occurred. RESULTS: A total of 472 patients were included. Age and Injury Severity Score did not differ between rural and urban patients. The pre-hospital time intervals and distances to trauma centers were longer for rural patients and a larger proportion of urban patients had intentional injuries (23.5% vs. 9.3%, P <0.001). The 30-day mortality for severely injured patients (Injury Severity Score >15) was 23.9% in urban and 13.3% in rural municipalities. In the multivariate regression analysis the odds ratio (OR) for 30-day mortality was 2.8 (95% confidence interval 1.0 to 7.9, P = 0.05) in urban municipalities. There was no difference in the length of ICU stay or scores. Twenty patients died on scene or during transportation and 56 missions were aborted because of pre hospital death. CONCLUSIONS: The severely injured urban trauma patients had a trend toward higher 30-day mortality compared with patients injured in rural areas but the length of ICU stay was similar. However, more pre-hospital deaths occurred in rural municipalities. The time before mobile ICU arrival appears to be critical for trauma patients' survival, especially in rural areas. PMID- 26542685 TI - Determinants of favourable opinions about euthanasia in a sample of French physicians. AB - BACKGROUND: The question whether euthanasia should be legalised has led to substantial public debate in France. The objective of this study in a sample of French physicians was to establish the potential determinants of a favourable opinion about euthanasia in general and when faced with a specific situation as embodied in the Humbert affair. METHODS: The study was a cross-sectional survey investigating two different samples of medical doctors: (1) those specialised in palliative care and affiliated to the French Society for Patient Accompaniment and Palliative Care; (2) medical interns (medical doctors in training course) in a French medical university (Marseille). A questionnaire was sent (email) to each voluntary participant including sociodemographics, professional status, mention of believing in God, and opinion about euthanasia (the question was designed to assess the general opinion about euthanasia and the opinion about a specific case, the Vincent Humbert' case (a man who was rendered quadriplegic, blind, and mute after an accident and has requested euthanasia). RESULTS: A total of 413 physicians participated in the research (participation rate: 48.5%). Less than half of the population were favourable to euthanasia in general and almost two thirds of the population were favourable to Vincent Humbert's request for euthanasia. Based on the multivariate analysis, individuals believing in God and being a medical intern were significant independent factors linked to having a favourable opinion about euthanasia in general and about the Vincent Humbert's request. DISCUSSION: There is still no study in France on the development of opinion about euthanasia and its impact. The issue goes beyond the strictly professional sphere and involves broader socio-political stakes. These stakes do not necessarily take into account medical practices and experiences or the desires of end-of-life patients. The professional upheaval that the future French legal framework will doubtlessly trigger will require further research. CONCLUSION: The professional upheaval that the future French legal framework will doubtlessly trigger will require further research. PMID- 26542686 TI - Late follicular progesterone to estradiol ratio is not influenced by protocols or gonadotropins used. AB - OBJECTIVE: Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate. STUDY DESIGN AND METHODS: A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level. MAIN RESULTS: One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7 +/- 923.2 vs. 1342.9 +/- 1223; P = 0.003 and 0.48 +/- 0.31 vs. 0.83 +/- 0.87; P = 0.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC = 0.632, p = 0.02 and 95 % CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45. CONCLUSION: Endometrial receptivity is determined by the complex interactions of E2 and P. PMID- 26542687 TI - Unusual presentation of a retained foreign body in a child. AB - A 4-year-old boy, not known to have any medical illness, presented to several medical facilities reporting right upper quadrant and right flank pain, intermittent fever and chills for 3 months. A CT of the abdomen showed that a swallowed 'bobby pin' had pierced through the right kidney. This finding explained the boy's symptoms. The pin was removed by laparotomy without any subsequent complication. The patient had an uneventful postoperative recovery. PMID- 26542688 TI - Financial Dependence of Young Adults with Childhood ADHD. AB - This study used data from the Pittsburgh ADHD Longitudinal Study (PALS) to evaluate financial outcomes of young adults (YA) with ADHD relative to comparisons. Participants for this study included 309 individuals who had been diagnosed with ADHD (DSM-III-R or DSM-IV) in childhood and 208 comparison YA without childhood ADHD diagnoses (total N = 517) who were followed through age 25. Participants were predominately male (88 %) and Caucasian (84 %). Diagnostic interviews were conducted in childhood. Young adults and their parents reported on financial outcomes and a number of predictor variables. Young adults with ADHD experienced greater financial dependence on family members (p < 0.05) and the welfare system (p < 0.01) and had lower earnings (p < 0.05) than comparisons. ADHD diagnostic status, education attainment, and delinquency were significant predictors of financial outcomes. A projection of lifetime earnings indicated that ADHD group participants could expect to earn $543,000-$616,000 less over their lifetimes than comparisons. Due to the propensity of individuals with ADHD to underreport problems, the data are likely to be underestimates. These findings support the need for interventions to improve labor market outcomes as well as the development of interventions that target the management of personal finances for individuals with ADHD in young adulthood. PMID- 26542690 TI - Risperidone, quetiapine and chlorpromazine may have induced priapism in an adolescent. AB - Priapism is the prolonged, painful erection of penile tissue not accompanied by sexual arousal. Priapism has been established as a rare adverse drug reaction to drugs such as antipsychotics, psychostimulants, antidepressants, and mood stabilizers. Immediate intervention is needed to prevent destructive and irreversible complications, such as erectile dysfunction, disfigurement, inability of the penis to stay erect, and related social/emotional problems. Antipsychotic-induced priapism may result from the alpha receptor occupancy property of those drugs. We report the case of a 13-year-old suffering from attention deficit-hyperactivity disorder plus conduct disorder with priapism related to antipsychotics. Episodes occurred with risperidone plus methylphenidate, quetiapine plus methylphenidate, and chlorpromazine alone. PMID- 26542691 TI - Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Status of collateral circulation is a strong predictor of outcome after acute ischemic stroke. Our aim was to compare the predictive value of strategies for collateral blood flow assessment with dynamic computed tomographic angiography (CTA) and conventional single-phase CT angiography. METHODS: Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT, single-phase CTA and whole brain CT perfusion/dynamic CTA within 9 hours after stroke onset. We defined poor outcome as a score on the modified Rankin Scale score of >=3. The association between collateral score and clinical outcome at 3 months was analyzed with Poisson regression. The prognostic value of collateral scoring with dynamic CTA and single-phase CTA in addition to age, stroke severity, and noncontrast CT was assessed with logistic regression and summarized with the area under the curve. RESULTS: Seventy patients were included, with a mean age of 68 years. We observed an increased risk of poor outcome in patients with poor collaterals on single-phase CTA (risk ratio, 1.8; 95% confidence interval, 1.0-3.1) and on dynamic CTA (risk ratio, 2.0; 95% confidence interval, 1.5-2.7). The prediction of poor clinical outcome by means of collateral adjustment was better with dynamic CTA (area under the curve, 0.84; likelihood ratio test P<0.01) than by single-phase CTA (area under the curve, 0.80; likelihood ratio test P=0.33). CONCLUSIONS: Collateral assessment with dynamic CTA better predicts clinical outcome at 3 months than single-phase conventional CTA. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl/trialreg. Unique identifier: NTR1804. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113. PMID- 26542689 TI - Sporadic multiple parathyroid gland disease--a consensus report of the European Society of Endocrine Surgeons (ESES). AB - BACKGROUND: Sporadic multiglandular disease (MGD) has been reported in literature in 8-33 % of patients with primary hyperparathyroidism (pHPT). This paper aimed to review controversies in the pathogenesis and management of sporadic MGD. METHODS: A literature search and review was made to evaluate the level of evidence concerning diagnosis and management of sporadic MGD according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled 'Hyperparathyroidism due to multiple gland disease: An evidence-based perspective'. RESULTS: Literature reports no prospective randomised studies; thus, a relatively low level of evidence was achieved. Appropriate surgical therapy of sporadic MGD should consist of a bilateral approach in most patients. Unilateral neck exploration guided by preoperative imaging should be reserved for selected patients, performed by an experienced endocrine surgeon and monitored by intraoperative parathormone assay (levels of evidence III-V, grade C recommendation). There is conflicting or equally weighted levels IV-V evidence supporting that cure rates can be similar or worse for sporadic MGD than for single adenomas (no recommendation). Best outcomes can be expected if surgery is performed by an experienced parathyroid surgeon working in a high-volume centre (grade C recommendation). Levels IV-V evidence supports that recurrent/persistence pHPT occurs more frequently in patients with double adenomas hence in situations where a double adenoma has been identified, the surgeon should have a high index of suspicion during surgery and postoperatively for the possibility of a four-gland disease (grade C recommendation). CONCLUSIONS: Identifying preoperatively patients at risk for MGD remains challenging, intraoperative decisions are important for achieving acceptable cure rates and long-term follow-up is mandatory in such patients. PMID- 26542692 TI - Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip. AB - BACKGROUND AND PURPOSE: Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. METHODS: We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. RESULTS: In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of individual data, interleukin-27 subunit alpha, growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001). CONCLUSIONS: Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke. PMID- 26542694 TI - Letter by Galyfos et al Regarding Article, "Periprocedural Myocardial Infarction After Carotid Endarterectomy and Stenting: Systematic Review and Meta-Analysis". PMID- 26542693 TI - Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury. AB - BACKGROUND AND PURPOSE: The extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood. METHODS: We performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke. RESULTS: We identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17*10(-7); rs31924033, P=5.61*10(-6); rs32249495, P=2.08*10(-7); and rs3677406, P=9.56*10(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia. CONCLUSIONS: Genetic variations of ANGPT1 and ZBTB7C are associated with increased infarct size in both mice and humans. ZBTB7C may modulate the ischemic response via neuronal apoptosis and dynamic collateralization and, in addition to ANGPT1, may serve as potential novel targets for treatments of cerebral ischemia. PMID- 26542696 TI - Response to Letter Regarding Article, "Periprocedural Myocardial Infarction After Aarotid Endarterectomy and Stenting: Systematic Review and Meta-Analysis". PMID- 26542695 TI - Examining Differences in Patterns of Sensory and Motor Recovery After Stroke With Robotics. AB - BACKGROUND AND PURPOSE: Developing a better understanding of the trajectory and timing of stroke recovery is critical for developing patient-centered rehabilitation approaches. Here, we quantified proprioceptive and motor deficits using robotic technology during the first 6 months post stroke to characterize timing and patterns in recovery. We also make comparisons of robotic assessments to traditional clinical measures. METHODS: One hundred sixteen subjects with unilateral stroke were studied at 4 time points: 1, 6, 12, and 26 weeks post stroke. Subjects performed robotic assessments of proprioceptive (position sense and kinesthesia) and motor function (unilateral reaching task and bimanual object hit task), as well as several clinical measures (Functional Independence Measure, Purdue Pegboard, and Chedoke-McMaster Stroke Assessment). RESULTS: One week post stroke, many subjects displayed proprioceptive (48% position sense and 68% kinesthesia) and motor impairments (80% unilateral reaching and 85% bilateral movement). Interindividual recovery on robotic measures was highly variable. However, we characterized recovery as early (normal by 6 weeks post stroke), late (normal by 26 weeks post stroke), or incomplete (impaired at 26 weeks post stroke). Proprioceptive and motor recovery often followed different timelines. Across all time points, robotic measures were correlated with clinical measures. CONCLUSIONS: These results highlight the need for more sensitive, targeted identification of sensory and motor deficits to optimize rehabilitation after stroke. Furthermore, the trajectory of recovery for some individuals with mild to moderate stroke may be much longer than previously considered. PMID- 26542697 TI - Phone and Video-Based Modalities of Central Blinded Adjudication of Modified Rankin Scores in an Endovascular Stroke Trial. AB - BACKGROUND AND PURPOSE: The standard outcome measure in stroke research is modified Rankin scale (mRS) evaluated by local blinded investigators. We aimed to assess feasibility and reliability of 2 central adjudication methods of mRS in the setting of a randomized endovascular stroke trial. METHODS: This is a secondary analysis derived from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) trial cohort. Primary outcome was distribution of mRS at 90 days. Local evaluation was done by certified investigators masked to treatment assignment using structured face-to-face interviews. In addition, central assessment was performed by 2 independent raters via structured phone interview (n=120) and via video recordings of the face-to-face interviews with local investigators (n=106). Interrater agreement was evaluated using kappa and discordance statistics. Sensitivity analyses for the primary end point using different adjudication approaches were performed. Correlation between mRS obtained with each modality and 24-hour follow-up infarct volumes was studied. RESULTS: Using local evaluation as the reference, higher agreement rates were noted with central video than with central phone evaluations (kw 0.92 [0.88-0.96] versus 0.77 [0.72-0.83]). Discrepancies in mRS scoring between local and central raters (phone- and video-based) were similar in both treatment allocation arms. Sensitivity analyses showed benefit of endovascular treatment irrespective of adjudication method, but higher odds ratios were observed with local evaluations. Final infarct volume was similarly correlated with mRS across all 3 evaluation modalities. CONCLUSIONS: Central adjudication of mRS is feasible, reducing interrater variability and avoiding potential problems related to lack of blinding. Our findings may have implications in the planning of future randomized acute stroke trials, especially in those including nonpharmacological interventions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379. PMID- 26542699 TI - Retraction Note: TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics. PMID- 26542700 TI - GP numbers are not shrinking but demand is swallowing the extra workforce, MPs told. PMID- 26542701 TI - [Report of the working group on uropathology of the German Society of Pathology 2015]. PMID- 26542698 TI - Value of Computed Tomographic Perfusion-Based Patient Selection for Intra Arterial Acute Ischemic Stroke Treatment. AB - BACKGROUND AND PURPOSE: The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. METHODS: We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core <70 mL; penumbra core >1.2; penumbra core >10 mL). RESULTS: The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71-0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66-0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92-1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. CONCLUSIONS: CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy. PMID- 26542702 TI - A derived transformation of emotional functions using self-reports, implicit association tests, and frontal alpha asymmetries. AB - Research on the derived transformation of stimulus functions (ToF) typically employs single dependent measures for assessing the stimulus functions after derived relations have been established. For the first time, we examined ToF using three dependent measures both prior to and after relational training and testing. Specifically, we employed self-reports, implicit association tests, and frontal alpha asymmetry as pre versus post measures for assessing ToF. First, we trained two abstract shapes as contextual cues for happier-than and unhappier than relations, respectively. Next, four conditional discriminations (A+/B-, B+/C , C+/D-, and D+/E-) were trained in the presence of the happier-than cue only, where A, B, C, D, and E were blurred faces. This was followed by tests for contextually controlled transitive inference (TI) in the presence of both the happier-than and unhappier-than cues. For the participants who demonstrated TI, performance across all three measures following relational training and testing indicated that the "happiness" functions of the A/B stimuli were greater than those of the D/E stimuli. This constitutes the first known demonstration of emotional ToF along explicit, implicit, and neurophysiological measures concurrently. PMID- 26542703 TI - Operant avoidance learning in crayfish, Orconectes rusticus: Computational ethology and the development of an automated learning paradigm. AB - Research in crustaceans offers a valuable perspective for studying the neural implementation of conserved behavioral phenomena, including motivation, escape, aggression, and drug-sensitive reward. The present work adds to this literature by demonstrating that crayfish successfully learn to respond to spatially contingent cues. An integrated video-tracking system automatically delivered a mild electric shock when a test animal entered or remained on a substrate paired with punishment. Following a few instances of shock delivery, crayfish quickly learned to avoid these areas. Comparable changes in substrate preference were not exhibited by yoked controls, but locomotion differed significantly from both pre conditioning levels and from those of their masters receiving shock in a contingent fashion. The results of this work provide valuable insights into the principles governing avoidance learning in an invertebrate system and provide a behavioral template for exploring the neural changes during associative learning. Serving as a case study, this project introduces a new computer framework for the automated control of learning paradigms. Based on routines contained within the JavaGrinders library (free download at iEthology.com), it integrates real-time video tracking with robotic interfaces, and provides a suitable framework for implementing automated learning paradigms. PMID- 26542705 TI - Effect of bromocriptine alginate nanocomposite (BANC) on a transgenic Drosophila model of Parkinson's disease. AB - The effect of bromocriptine, a dopamine agonist, administered in the form of bromocriptine alginate nanocomposite (BANC) was studied on Parkinson's disease (PD) model flies. The synthesized BANC was subject to characterization and, at a final concentration of 0.5, 1.0 and 1.5 uM, was mixed in diet. The PD flies were allowed to feed on it for 24 days. A significant dose-dependent delay in the loss of climbing activity and activity pattern was observed in PD flies exposed to 0.5, 1.0 and 1.5 uM BANC. The PD flies exposed to BANC also showed a significant reduction in lipid peroxidation and glutathione-S-transferase activity, and an increase in glutathione content. However, no gross morphological changes were observed in the brains of PD flies compared with controls. The results suggest that BANC is effective in reducing the PD symptoms in these transgenic flies. PMID- 26542706 TI - The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells. AB - Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. PMID- 26542708 TI - A Patient-Based Nomogram for Predicting Overall Survival after Radiofrequency Ablation for Hepatocellular Carcinoma. AB - PURPOSE: To develop a prognostic nomogram based on specific patient and tumor factors capable of estimating individual survival outcomes after radiofrequency (RF) ablation as a primary therapy for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 893 patients who were initially treated with curative RF ablation for HCC; patients were temporally divided into derivation (n = 607) and validation (n = 286) cohorts. A multivariate Cox proportional hazards model for overall survival was developed and validated. The discriminatory accuracy of the model was compared with the preexisting Cancer of the Liver Italian Program (CLIP) system and the Tokyo score previously proposed for percutaneous therapy for HCC by analyzing receiver operating characteristic (ROC) curves. RESULTS: A nomogram was generated for 3-year survival, incorporating largest tumor diameter and number of tumors, serum albumin and creatinine, platelet count, prothrombin time, and serum alpha-fetoprotein on a logarithmic scale. It had good calibration and discrimination abilities with a C index of 0.74. The validation results also showed that the nomogram performed well in terms of goodness-of-fit and discrimination (C-index, 0.72). Analysis of ROC curves in the validation cohort indicated that the model had better predictive power than CLIP and Tokyo scores (C-indexes, 0.54 and 0.66, respectively). CONCLUSIONS: This prognostic tool quantifying per-patient expected survival after RF ablation can be used in daily clinical decision making with regard to patients with HCC deemed suitable for radical ablation and is probably more reliable than existing guidelines. PMID- 26542709 TI - Improved electroporation procedure for genetic transformation of Dekkera/Brettanomyces bruxellensis. AB - Yeast Dekkera/Brettanomyces bruxellensis is one of the most common contaminants in wine industry, but also one of the most promising candidates for large-scale bioethanol production. Brettanomyces bruxellensis not only produces and tolerates high ethanol concentrations, but can also ferment cellobiose and adapt to lignocellulose hydrolasate. Furthermore, genome sequences of several B. bruxellensis strains are available, and efforts have been made to develop tools for genetic transformation of this yeast. Previously, we reported a successful transformation using lithium acetate/PEG method and electroporation, however, with very low transformation efficiency (10-20 transformants MUg(-1)). Here we describe an optimization of electroporation procedure which resulted in a significant increase of transformation efficiency (2.8 * 10(3) transformants MUg( 1)). Several key transformation parameters were optimized including cell growth phase, density of cells in the transformation sample and electroporation settings. We determined that treating the cells with both lithium acetate (100 mM) and dithiothreitol (35 mM) synergistically improves transformation efficiency. Using the described procedure around 500 transformants can be obtained per transformation sample with 180 ng of non-homologous linear transforming fragment. Additionally, several transformants were obtained with less than 1 ng of DNA demonstrating that this procedure is adequate even when very limited amount of DNA is available. PMID- 26542704 TI - Non-muscle myosin II in disease: mechanisms and therapeutic opportunities. AB - The actin motor protein non-muscle myosin II (NMII) acts as a master regulator of cell morphology, with a role in several essential cellular processes, including cell migration and post-synaptic dendritic spine plasticity in neurons. NMII also generates forces that alter biochemical signaling, by driving changes in interactions between actin-associated proteins that can ultimately regulate gene transcription. In addition to its roles in normal cellular physiology, NMII has recently emerged as a critical regulator of diverse, genetically complex diseases, including neuronal disorders, cancers and vascular disease. In the context of these disorders, NMII regulatory pathways can be directly mutated or indirectly altered by disease-causing mutations. NMII regulatory pathway genes are also increasingly found in disease-associated copy-number variants, particularly in neuronal disorders such as autism and schizophrenia. Furthermore, manipulation of NMII-mediated contractility regulates stem cell pluripotency and differentiation, thus highlighting the key role of NMII-based pharmaceuticals in the clinical success of stem cell therapies. In this Review, we discuss the emerging role of NMII activity and its regulation by kinases and microRNAs in the pathogenesis and prognosis of a diverse range of diseases, including neuronal disorders, cancer and vascular disease. We also address promising clinical applications and limitations of NMII-based inhibitors in the treatment of these diseases and the development of stem-cell-based therapies. PMID- 26542710 TI - Identification and characterization of Csh3 as an SH3 protein that interacts with fission yeast Cap1. AB - Schizosaccharomyces pombe Cap1 has been identified as the (adenylyl) cyclase associated protein. Cap1 was able to bind Cap1 itself and actin. Cap1 localized at the growing tip, and this localization was dependent on the Cap1 P2 region. In a two-hybrid screening using cap1 as bait, we isolated csh3, which encodes a protein of 296 amino acids with an SH3 domain and a proline/glutamine-rich region. The binding of Csh3 and Cap1 was confirmed by in vivo pull down assays. Cooperative functions of Csh3 and Cap1 were observed. Deletion of both csh3 and cap1 resulted in heightened sensitivity to CaCl2, while disruption of either gene alone did not have any effect in this regard. In addition, over-expression of csh3 or cap1 alone did not affect cell growth, while over-expression of both genes resulted in growth retardation. Finally, while Csh3-GFP localized to the cytoplasm in wild-type cells, its localization was altered in cap1Delta cells, suggesting that the interaction between Csh3 and Cap1 controls the cellular localization of Csh3. These results demonstrate that Cap1 in Schizo. pombe is a multifunctional protein that functions through interaction with Cap1 itself and other proteins including adenylyl cyclase, actin and Csh3. PMID- 26542711 TI - Single-Cell Western Blotting. AB - Little headway has been made in single cell protein analysis, aside from tools that rely solely on antibody-probe based detection (i.e., flow cytometry, immunocytochemistry), which are limited by low specificity and multiplexing capabilities. To address these protein analysis gaps, we have introduced a single cell western blot (scWestern). The protein assay is capable of highly specific analysis by coupling antibody-based detection with a polyacrylamide gel electrophoresis (PAGE) protein separation. Cells are settled via gravity into polyacrylamide (PA) microwells, chemically lysed in the wells, and then subjected to PAGE through the walls of the microwells and into the surrounding PA gel. Over a thousand single-cell separations are performed simultaneously, and multiple protein targets of interest are investigated. After PAGE separation, photo immobilization of all proteins to the gel allows for antibody probing and lends to the archival quality of the scWestern assay where new proteins targets can be investigated months after the initial separations are performed. PMID- 26542712 TI - A Microfluidic Device for Immunoassay-Based Protein Analysis of Single E. coli Bacteria. AB - We present a method suitable for quantitative analysis of intracellular proteins, metabolites and secondary messengers of single bacterial cells. The method integrates the concept of immunoassays on a microfluidic device that facilitates single cell trapping and isolating in a small volume of a few tens of picoliters. Combination of the benefits of microfluidic systems for single cell analysis with the high analytical selectivity and sensitivity of immunoassays enables the detection of even low abundant intracellular analytes which occur only at a few hundred copies per bacterium. PMID- 26542707 TI - The role of prolactin in andrology: what is new? AB - Prolactin (PRL) has been long deemed as a hormone involved only in female reproduction. However, PRL is a surprising hormone and, since its identification in the 1970s, its attributed functions have greatly increased. However, its specific role in male health is still widely unknown. Recently, low PRL has been associated with reduced ejaculate and seminal vesicle volume in infertile subjects. In addition, in men consulting for sexual dysfunction, hypoprolactinemia has been associated with erectile dysfunction and premature ejaculation, findings further confirmed in the general European population and infertile men. Several metabolic derangements, recapitulating metabolic syndrome, have also been associated with low PRL both in men with sexual dysfunction and from the general European population. In men with sexual dysfunction, followed-up for more than 4 years, low PRL was identified as an independent predictor of the incidence of major adverse cardiovascular events. Finally, an association with anxiety or depressive symptoms has been found in men with sexual dysfunction and from the general European population. While a direct role for impaired PRL function in the pathogenesis of these reproductive, sexual, metabolic and psychological disorders is conceivable, the possibility that low PRL is a mirror of an increased dopaminergic or a decreased serotonergic tone cannot be ruled out. Hyperactivity of the dopaminergic system can explain only a few of the aforementioned findings, whereas a hypo-serotonergic tone fits well with the clinical features associated with low PRL, and there is significant evidence supporting the hypothesis that PRL could be a mirror of serotonin in the brain. PMID- 26542713 TI - Enzyme-Linked ImmunoSpot (ELISpot) for Single-Cell Analysis. AB - The ELISpot, a heterogeneous immunoassay, is widely used for detection of low abundant analytes. It is a reliable and robust assay to monitor responses of the immune system at the single-cell level by capturing secreted molecules of interest with specific, membrane-bound antibodies. Those molecules are then made visible by a cascade of ELISA-related development steps. The final results are distinct spots on the membrane as an imprint of the cell secreting the captured molecules, not only allowing their quantification but also providing insight on the kinetics and strength of secretion. This chapter describes the optimized protocol steps of the ELISpot technique, important improvements and tools available for the community, and the current expansion of the technique into polyfunctional cell analysis. PMID- 26542714 TI - Photocleavable DNA Barcoding Antibodies for Multiplexed Protein Analysis in Single Cells. AB - We describe a DNA-barcoded antibody sensing technique for single cell protein analysis in which the barcodes are photocleaved and digitally detected without amplification steps (Ullal et al., Sci Transl Med 6:219, 2014). After photocleaving the unique ~70 mer DNA barcodes we use a fluorescent hybridization technology for detection, similar to what is commonly done for nucleic acid readouts. This protocol offers a simple method for multiplexed protein detection using 100+ antibodies and can be performed on clinical samples as well as single cells. PMID- 26542715 TI - Genome-Wide Analysis of Protein and mRNA Copy Numbers in Single Escherichia coli Cells with Single-Molecule Sensitivity. AB - Single-cell proteomic and transcriptomic analysis is an emerging approach for providing quantitative and comprehensive characterization of gene functions in individual cells. This analysis, however, is often hampered by insufficient sensitivity for detecting low copy gene expression products such as transcription factors and regulators. Here I describe a method for the quantitative genome-wide analysis of single-cell protein and mRNA copy numbers with single molecule sensitivity for the model organism Escherichia coli. PMID- 26542716 TI - Microfluidic Flow Cytometry for Single-Cell Protein Analysis. AB - Flow-cytometric (FC) detection of proteins in single cells is a rapid, quantitative method for single-cell protein analysis. Recent advancements in microfluidic technologies have leveraged miniaturization and automation to adapt flow cytometry for analyzing single cell protein profiles both for cell surface and intracellular proteins. Here, we describe the method for microfluidic FC, along with instructions to build a microfluidic platform capable of automated cell culture, cell surface receptor immunostaining, intracellular phosphoprotein and intracellular cytokine immunostaining, and analysis using micro-flow cytometry. As a demonstration of our platform and protocol, we detail the profiling of TLR4 receptor activation, ERK1/2 phosphorylation, and TNFalpha production in LPS stimulated macrophages using the microfluidic platform. PMID- 26542717 TI - Microfluidic Image Cytometry for Single-Cell Phenotyping of Human Pluripotent Stem Cells. AB - A microfluidic human pluripotent stem cell (hPSC) array has been developed for robust and reproducible hPSC culture methods to assess chemically defined serum- and feeder-free culture conditions. This microfluidic platform, combined with image cytometry, enables the systematic analysis of multiple simultaneously detected marker expression in individual cells, for screening of various chemically defined media across hPSC lines, and the study of phenotypic responses. PMID- 26542718 TI - Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry. AB - Single cell mass cytometry is revolutionizing our ability to quantitatively characterize cellular biomarkers and signaling networks. Mass cytometry experiments routinely measure 25-35 features of each cell in primary human tissue samples. The relative ease with which a novice user can generate a large amount of high quality data and the novelty of the approach have created a need for example protocols, analysis strategies, and datasets. In this chapter, we present detailed protocols for two mass cytometry experiments designed as training tools. The first protocol describes detection of 26 features on the surface of human peripheral blood mononuclear cells. In the second protocol, a mass cytometry signaling network profile measures 25 node states comprised of five key signaling effectors (AKT, ERK1/2, STAT1, STAT5, and p38) quantified under five conditions (Basal, FLT3L, SCF, IL-3, and IFNgamma). This chapter compares manual and unsupervised data analysis approaches, including bivariate plots, heatmaps, histogram overlays, SPADE, and viSNE. Data files in this chapter have been shared online using Cytobank ( http://www.cytobank.org/irishlab/ ). PMID- 26542719 TI - Multiplexed Peptide-MHC Tetramer Staining with Mass Cytometry. AB - Mass cytometry is flow cytometry based on single cell mass spectrometry with decreased crosstalk between channels and an ability to probe >40 parameters per cell, making it well suited for multiplexed assays. Peptide major histocompatibility (MHC) tetramer staining allows direct detection of antigen specific cells and is also amenable to multiplexing/combinatorial approaches. Here we describe methods for multiplexed pMHC-tetramer staining using mass cytometry. PMID- 26542720 TI - Imaging and Mapping of Tissue Constituents at the Single-Cell Level Using MALDI MSI and Quantitative Laser Scanning Cytometry. AB - For nearly a century, histopathology involved the laborious morphological analyses of tissues stained with broad-spectrum dyes (i.e., eosin to label proteins). With the advent of antibody-labeling, immunostaining (fluorescein and rhodamine for fluorescent labeling) and immunohistochemistry (DAB and hematoxylin), it became possible to identify specific immunological targets in cells and tissue preparations. Technical advances, including the development of monoclonal antibody technology, led to an ever-increasing palate of dyes, both fluorescent and chromatic. This provides an incredibly rich menu of molecular entities that can be visualized and quantified in cells-giving rise to the new discipline of Molecular Pathology. We describe the evolution of two analytical techniques, cytometry and mass spectrometry, which complement histopathological visual analysis by providing automated, cellular-resolution constituent maps. For the first time, laser scanning cytometry (LSC) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) are combined for the analysis of tissue sections. The utility of the marriage of these techniques is demonstrated by analyzing mouse brains with neuron-specific, genetically encoded, fluorescent proteins. We present a workflow that: (1) can be used with or without expensive matrix deposition methods, (2) uses LSC images to reveal the diverse landscape of neural tissue as well as the matrix, and (3) uses a tissue fixation method compatible with a DNA stain. The proposed workflow can be adapted for a variety of sample preparation and matrix deposition methods. PMID- 26542721 TI - SPLIFF: A Single-Cell Method to Map Protein-Protein Interactions in Time and Space. AB - Protein interactions occur at certain times and at specific cellular places. The past years have seen a massive accumulation of binary protein-protein interaction data. The rapid increase of this context-free information necessitates robust methods to monitor protein interactions with temporal and spatial resolution in single cells. We have developed a simple split-ubiquitin-based method (SPLIFF) that uses the ratio of two fluorescent reporters as a signal for protein-protein interactions. One protein of the pair of interest is attached to the linear fusion of mCherry, the C-terminal half of ubiquitin, and GFP (mCherry-Cub-GFP). The other potential binding partner is expressed as a C-terminal fusion to the N terminal half of ubiquitin (Nub). Upon co-expression the interaction between the two proteins of interest induces the reassociation of Nub and Cub to the native like ubiquitin. GFP is subsequently cleaved from the C-terminus of Cub and degraded whereas the red-fluorescent mCherry stays attached to the Cub-fusion protein. We first implemented this method in the model yeast Saccharomyces cerevisiae. One fusion protein is expressed in cells of the a-mating type and the complementary fusion protein in cells of the alpha-mating type. Upon mixing, both cell types fuse and the Nub- and Cub-fusion proteins are free to interact. The red and green fluorescence is monitored by two-channel fluorescence time-lapse microcopy. The moment of cell fusion defines the start of the analysis. The calculated ratio of green to red fluorescence allows mapping the spatiotemporal interaction profiles of the investigated proteins in single cells. PMID- 26542722 TI - Microfluidic Proximity Ligation Assay for Profiling Signaling Networks with Single-Cell Resolution. AB - The proximity ligation assay (PLA) is a technique that can be used to characterize proteins, protein-protein interactions, and protein modifications at the single-cell level. Image-based in situ detection of proteins using PLA is a quantitative method with a high degree of sensitivity and specificity. The miniaturization and parallelization of the PLA onto a microfluidic chip and concurrent use of an automated cell-culture system increase the throughput of this technology. Here, we describe the performance of PLA on a microfluidic chip. We provide protocols for on-chip cell culture, time-shifted cell stimulation and fixation, PLA implementation, and computational image analysis in order to achieve single-cell resolution. As a proof of concept, we studied the phosphorylation of Akt in response to stimulation with platelet-derived growth factor. PMID- 26542723 TI - Dynamics and Interactions of Individual Proteins in the Membrane of Single, Living Cells. AB - Total internal reflection fluorescence (TIRF) microscopy is a powerful technique for interrogating protein dynamics in the membranes of living single cells. Receptor-ligand interactions are of particular interest for improving our understanding of cell signaling networks in a variety of applications. Here, we describe methods for fluorescently labeling individual receptors and their ligands, conducting single-molecule TIRF microscopy of receptors and ligands in single, living cells, and importantly, performing image analysis on the resulting time sequence of images to extract quantitative dynamics. While we use Toll-like receptor 4 and its ligand lipopolysaccharide as a specific example, the methods are general and readily extendable to other receptor-ligand systems of importance in cellular biology. PMID- 26542724 TI - Microfluidics-Enabled Enzyme Activity Measurement in Single Cells. AB - Cellular heterogeneity has presented a significant challenge in the studies of biology. While most of our understanding is based on the analysis of ensemble average, individual cells may process information and respond to perturbations very differently. Presented here is a highly sensitive platform capable of measuring enzymatic activity at the single-cell level. The strategy innovatively combines a rolling circle-enhanced enzyme activity detection (REEAD) assay with droplet microfluidics. The single-molecule sensitivity of REEAD allows highly sensitive detection of enzymatic activities, i.e. at the single catalytic event level, whereas the microfluidics enables isolation of single cells. Further, confined reactions in picoliter-sized droplets significantly improve enzyme extraction from human cells or microorganisms and result in faster reaction kinetics. Taken together, the described protocol is expected to open up new possibilities in the single-cell research, particularly for the elucidation of heterogeneity in a population of cells. PMID- 26542725 TI - Microfluidic Chemical Cytometry for Enzyme Assays of Single Cells. AB - Cellular heterogeneity occurs, and should be probed, at multiple levels of cellular structure and physiology from the genome to enzyme activity. In particular, single-cell measures of protein levels are complemented by single cell measurements of the activity of these proteins. Microfluidic assays of enzyme activity at the single-cell level combine moderate to high throughput with low dead volumes and the potential for automation. Herein, we describe the steps required to fabricate and operate a microfluidic device for chemical cytometry of fluorescent or fluorogenic reporters of enzyme activity in individual cells. PMID- 26542726 TI - Quantitative Detection of Nucleocytoplasmic Transport of Native Proteins in Single Cells. AB - The detection of protein translocation (i.e., the movement of intracellular proteins among various subcellular compartments) conventionally relies on imaging and subcellular-fractionation-based techniques that do not generate information on a large cell population with single-cell resolution. Although special flow cytometric tools such as imaging flow cytometry may generate single-cell data on processes such as nucleocytoplasmic transport, such equipment is expensive (thus has limited accessibility) and has low throughput for examining cells due to the reliance on high-speed imaging. Here we describe a protocol for detecting translocation of native proteins using a common flow cytometer which detects fluorescence intensity without imaging. We conduct chemical release of cytosolic proteins and fluorescence immunostaining of a targeted protein. The detected fluorescence intensity is quantitatively correlated to the cytosolic/nuclear localization of the protein at the single cell level. Our technique provides a simple route for studying nucleocytoplasmic transport with single-cell resolution using common flow cytometers. PMID- 26542727 TI - The CAT (COPD Assessment Test) questionnaire as a predictor of the evolution of severe COPD exacerbations. AB - INTRODUCTION: Since exacerbations of chronic obstructive pulmonary disease (COPD) cause both a great impact on the progression of the disease and generate high health expenditures, there is a need to develop tools to evaluate their prognosis. METHOD: Multicenter, observational, prospective study that evaluated the prognostic utility of the COPD Assessment Test (CAT) in severe exacerbations of COPD. Anthropometric and clinical variables were analyzed: smoking, history of exacerbations during the previous year, drug treatment, degree of baseline dyspnea, comorbidities; laboratory variables at admission (complete blood count, arterial blood gas and biochemistry) and CAT scores in the first 24 h of admission, on the third day, at discharge and at 3 months. RESULTS: We evaluated 106 patients (91 males) with a mean age of 71.1 (SD 9.8 years), mean FEV1 45.2% (14.7%) and average CAT score at admission of 24.7 points (7.1). At three months after discharge, treatment failure was observed in 39 (36.8%) patients: 14 (13.2%) presented an exacerbation without the need for hospital admission, 22 were readmitted (20.8%) and 3 (2.8%) died during follow-up. The three factors associated with increased risk of failure were a reduction less than 4 units in the CAT at discharge compared to admission, lower hemoglobin levels and treatment with domiciliary oxygen. CONCLUSIONS: A change of <=4 points in the CAT score at discharge compared to that obtained at admission due to a severe exacerbation of COPD, helps to predict therapeutic failure such as a new exacerbation, readmission or death in the subsequent three months. PMID- 26542728 TI - Undersized angioplasty and stenting of symptomatic intracranial tight stenosis with Enterprise: Evaluation of clinical and vascular outcome. AB - BACKGROUND: Severe intracranial arterial stenosis results in more than 10% incidence of stroke and transient ischemic attack. Using undersized angioplasty with off-label closed-cell Enterprise stent may be a feasible alternative option for treating patients with intracranial atherosclerotic disease who fail dual antiplatelet medical therapy. The results of the authors' study are presented in this paper. MATERIALS AND METHODS: Between January 2013 and July 2014, 24 symptomatic patients with a total of 30 intracranial arterial stenotic lesions refractory to medical therapy, who underwent undersized angioplasty and Enterprise stenting, were retrospectively reviewed in the authors' institution. The results evaluated include technical success rate, clinical outcome measured as modified Rankin Scale at presentation and follow-up, peri-procedural morbidity within 30 days and 1 year, and follow-up vessel patency. RESULTS: Stent deployment was successfully achieved in all stenotic lesions (30/30). Mean pre stent and post-stent diameter residual stenosis was 81% and 18%, respectively. The peri-procedural complication rate during 30 days after stenting was 10% per lesion (3/30), including intracranial hemorrhage, in-stent thrombosis and ischemic stroke. No further thromboembolic event or complication occurred in any patient more than 30 days after stenting. Modified Rankin scale <= 2 was observed in 64% and 83% of patients at initial presentation and follow-up (mean 15.8 months), respectively. Imaging follow-up was available in 17 of 24 patients (70.8%) and 20 of 30 treated lesions (66.6%) with a mean follow-up period of 15.4 months. Only one asymptomatic in-stent restenosis occurred in 20 available lesions (5.0%). CONCLUSION: This preliminary study suggests that using undersized angioplasty and Enterprise stenting may effectively treat high-degree symptomatic intracranial arterial stenosis with favorable clinical and angiographic outcome. PMID- 26542730 TI - Late Diagnosis of HIV Infection in Metropolitan Areas of the United States and Puerto Rico. AB - The majority of persons infected with HIV live in large metropolitan areas and many such areas have implemented intensified HIV testing programs. A national indicator of HIV testing outcomes is late diagnosis of HIV infection (stage 3, AIDS). Based on National HIV Surveillance System data, 23.3 % of persons with HIV diagnosed in 2012 had a late diagnosis in large MSAs, 26.3 % in smaller MSAs, and 29.6 % in non-metropolitan areas. In the 105 large MSAs, the percentage diagnosed late ranged from 13.2 to 47.4 %. During 2003-2012, the percentage diagnosed late decreased in large MSAs (32.2-23.3 %), with significant decreases in 41 of 105 MSAs overall and among men who have sex with men. Sustained testing efforts may help to continue the decreasing trend in late-stage HIV diagnosis and provide opportunities for early care and treatment and potential reduction in HIV transmission. PMID- 26542729 TI - Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer's disease patients. AB - RATIONALE: The G-protein-coupled relaxin family receptors RXFP1 and RXFP3 are widely expressed in the cortex and are involved in stress responses and memory and emotional processing. However, the identification of these receptors in human cortex and their status in Alzheimer's disease (AD), which is characterized by both cognitive impairments and neuropsychiatric behaviours, have not been reported. OBJECTIVES: In this study, we characterized RXFP receptors for immunoblotting and measured RXFP1 and RXFP3 immunoreactivities in the postmortem neocortex of AD patients longitudinally assessed for depressive symptoms. METHODS: RXFP1 and RXFP3 antibodies were characterized by immunoblotting with lysates from transfected HEK cells and preadsorption with RXFP3 peptides. Also, postmortem neocortical tissues from behaviourally assessed AD and age-matched controls were processed for immunoblotting with RXFP1 and RXFP3 antibodies. RESULTS: Compared to controls, putative RXFP1 immunoreactivity was reduced in parietal cortex of non-depressed AD patients but unchanged in depressed patients. Furthermore, putative RXFP3 immunoreactivity was increased only in depressed AD patients. RXFP1 levels in the parietal cortex also correlated with severity of depression symptoms. In contrast, RXFP1 and RXFP3 levels did not correlate with dementia severity or beta-amyloid burden. CONCLUSION: Alterations of RXFP1 and RXFP3 may be neurochemical markers of depression in AD, and relaxin family receptors warrant further preclinical investigations as possible therapeutic targets for neuropsychiatric symptoms in dementia. PMID- 26542731 TI - Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease. AB - Transcranial direct current stimulation (tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex. This simple and safe neurostimulation technique for modulating motor functions in Parkinson's disease could extend treatment option for patients with movement disorders. We assessed whether tDCS applied daily over the cerebellum (cerebellar tDCS) and motor cortex (M1-tDCS) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Nine patients (aged 60-85 years; four women; Hoehn & Yahr scale score 2-3) diagnosed as having idiopathic PD were recruited. To evaluate how tDCS (cerebellar tDCS or M1-tDCS) affects motor and cognitive function in PD, we delivered bilateral anodal (2 mA, 20 min, five consecutive days) and sham tDCS, in random order, in three separate experimental sessions held at least 1 month apart. In each session, as outcome variables, patients underwent the Unified Parkinson's Disease Rating Scale (UPDRS III and IV) and cognitive testing before treatment (baseline), when treatment ended on day 5 (T1), 1 week later (T2), and then 4 weeks later (T3), at the same time each day. After patients received anodal cerebellar tDCS and M1-tDCS for five days, the UPDRS IV (dyskinesias section) improved (p < 0.001). Conversely, sham tDCS, cerebellar tDCS, and M1-tDCS left the other variables studied unchanged (p > 0.05). Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients' levodopa-induced dyskinesias. PMID- 26542732 TI - Sunitinib modulates the radiosensitivity of esophageal squamous cell carcinoma cells in vitro. AB - This study aims to explore the radiosensitivity of sunitinib on esophageal cancer cell lines. For in vitro studies, human esophageal squamous cell carcinoma (ESCC) cell lines were treated with sunitinib 24 hours before irradiation. ESCC cell lines were treated with sunitinib with or without radiation. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis and cell cycle analysis were detected by flow cytometry. Deoxyribonucleic acid (DNA) double-strand breaks were performed by immunocytofluorescence analysis. Western blot analysis was used to determine the effect of sunitinib on radiation induced signal transduction. Sunitinib potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.13-1.72. Furthermore, sunitinib increased radiation induced DNA double-strand breaks, promoted the apoptosis of ESCC cells and induced the G2/M arrest. Radiosensitization was accompanied with enhanced apoptosis and regulated by the intrinsic pathway of apoptosis. Sunitinib sensitized ESCC cells to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in esophageal cancer. PMID- 26542733 TI - Differentially expressed small RNAs in Arabidopsis galls formed by Meloidogyne javanica: a functional role for miR390 and its TAS3-derived tasiRNAs. AB - Root-knot nematodes (RKNs) induce inside the vascular cylinder the giant cells (GCs) embedded in the galls. The distinctive gene repression in early-developing GCs could be facilitated by small RNAs (sRNA) such as miRNAs, and/or epigenetic mechanisms mediated by 24nt-sRNAs, rasiRNAs and 21-22nt-sRNAs. Therefore, the sRNA-population together with the role of the miR390/TAS3/ARFs module were studied during early gall/GC formation. Three sRNA libraries from 3-d-post inoculation (dpi) galls induced by Meloidogyne javanica in Arabidopsis and three from uninfected root segments were sequenced following Illumina-Solexa technology. pMIR390a::GUS and pTAS3::GUS lines were assayed for nematode dependent promoter activation. A sensor line indicative of TAS3-derived tasiRNAs binding to the ARF3 sequence (pARF3:ARF3-GUS) together with a tasiRNA-resistant ARF3 line (pARF3:ARF3m-GUS) were used for functional analysis. The sRNA population showed significant differences between galls and controls, with high validation rate and correspondence with their target expression: 21-nt sRNAs corresponding mainly to miRNAs were downregulated, whilst 24-nt-sRNAs from the rasiRNA family were mostly upregulated in galls. The promoters of MIR390a and TAS3, active in galls, and the pARF3:ARF3-GUS line, indicated a role of TAS3 derived-tasiRNAs in galls. The regulatory module miR390/TAS3 is necessary for proper gall formation possibly through auxin-responsive factors, and the abundance of 24-nt sRNAs (mostly rasiRNAs) constitutes a gall hallmark. PMID- 26542735 TI - Hierarchical MoS2 @Carbon Microspheres as Advanced Anodes for Li-Ion Batteries. AB - Hierarchical hybridized nanocomposites with rationally constructed compositions and structures have been considered key for achieving superior Li-ion battery performance owing to their enhanced properties, such as fast lithium ion diffusion, good collection and transport of electrons, and a buffer zone for relieving the large volume variations during cycling processes. Hierarchical MoS2 @carbon microspheres (HMCM) have been synthesized in a facile hydrothermal treatment. The structure analyses reveal that ultrathin MoS2 nanoflakes (ca. 2-5 nm) are vertically supported on the surface of carbon nanospheres. The reversible capacity of the HMCM nanocomposite is maintained at 650 mA h g(-1) after 300 cycles at 1 A g(-1) . Furthermore, the capacity can reach 477 mA h g(-1) even at a high current density of 4 A g(-1) . The outstanding electrochemical performance of HMCM is attributed to the synergetic effect between the carbon spheres and the ultrathin MoS2 nanoflakes. Additionally, the carbon matrix can supply conductive networks and prevent the aggregation of layered MoS2 during the charge/discharge process; and ultrathin MoS2 nanoflakes with enlarged surface areas, which can guarantee the flow of the electrolyte, provide more active sites and reduce the diffusion energy barrier of Li(+) ions. PMID- 26542734 TI - Function of Slit/Robo signaling in breast cancer. AB - Slit and Robo are considered tumor suppressors because they are frequently inactivated in various tumor tissue. These genes are closely correlated with CpG hypermethylation in their promoters. The Slit/Robo signaling pathway is reportedly involved in breast cancer development and metastasis. Overexpression of Slit/ Robo induces its tumor suppressive effects possibly by inactivating the beta-catenin/LEF/TCF and PI3K/Akt signaling pathways or by altering beta catenin/E-cadherin-mediated cell-cell adhesion in breast cancer cells. Furthermore, loss of Slit proteins or their Robo receptors upregulates the CXCL12/CXCR4 signaling axis in human breast carcinoma. In addition, this pathway regulates the distant migration of breast cancer cells not only by mediating the phosphorylation of the downstream molecules of CXCL12/CXCR4 and srGAPs, such as PI3K/ Src, RAFTK/ Pyk2, and CDC42, but also by regulating the activities of MAP kinases. This review includes recent studies on the functions of Slit/Robo signaling in breast cancer and its molecular mechanisms. PMID- 26542736 TI - Guanine nucleotide induced conformational change of Cdc42 revealed by hydrogen/deuterium exchange mass spectrometry. AB - Cdc42 regulates pathways related to cell division. Dysregulation of Cdc42 can lead to cancer, cardiovascular diseases and neurodegenerative diseases. GTP induced activation mechanism plays an important role in the activity and biological functions of Cdc42. P-loop, Switch I and Switch II are critical regions modulating the enzymatic activity of Cdc42. We applied amide hydrogen/deuterium exchange coupled with liquid chromatography mass spectrometry (HDXMS) to investigate the dynamic changes of apo-Cdc42 after GDP, GTP and GMP PCP binding. The natural substrate GTP induced significant decreases of deuteration in P-loop and Switch II, moderate changes of deuteration in Switch I and significant changes of deuteration in the alpha7 helix, a region far away from the active site. GTP binding induced similar effects on H/D exchange to its non-hydrolysable analog, GMP-PCP. HDXMS results indicate that GTP binding blocked the solvent accessibility in the active site leading to the decrease of H/D exchange rate surrounding the active site, and further triggered a conformational change resulting in the drastic decrease of H/D exchange rate at the remote alpha7 helix. Comparing the deuteration levels in three activation states of apo Cdc42, Cdc42-GDP and Cdc42-GMP-PCP, the apo-Cdc42 has the most flexible structure, which can be stabilized by guanine nucleotide binding. The rates of H/D exchange of Cdc42-GDP are between the GMP-PCP-bound and the apo form, but more closely to the GMP-PCP-bound form. Our results show that the activation of Cdc42 is a process of conformational changes involved with P-loop, Switch II and alpha7 helix for structural stabilization. PMID- 26542737 TI - Recycling organs - growing tailor-made replacement kidneys. PMID- 26542738 TI - Cryptochrome-dependent circadian periods in the arcuate nucleus. AB - The circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for controlling behavioral activity rhythms, such as a free running rhythm in constant darkness. Rodents have several circadian oscillators in other brain regions including the arcuate nucleus (ARC). In specific conditions such as food anticipatory activity rhythms in the context of timed restricted feeding, an alternative circadian pace-making system has been assumed by means of circadian oscillators like the SCN. Despite extensive lesion studies, the anatomic locations of extra-SCN circadian pacemakers responsible for regulating behavioral rhythms have not been found. In the present study, we investigated circadian rhythms in the SCN and extra-SCN region of the arcuate nucleus (ARC) by analyzing PER2::LUCIFERASE expression in specific regions from wild-type C57BL/6, Cry1(-/-), and Cry2(-/-) mice. Compared to wild-type animals, we observed period shortening in both the SCN and ARC of Cry1(-/-) mice and period lengthening in Cry2(-/-) mice. Interestingly, the periods in the ARC of both genotypes were identical to those in the SCN. Moreover, the amplitudes of PER2::LUC rhythms in the ARC of all animals were decreased compared to those in the SCN. These data suggest that the ARC is a candidate circadian pacemaker outside the SCN. PMID- 26542739 TI - An overview of pregnancy and fertility issues in breast cancer patients. AB - Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview. PMID- 26542740 TI - Toward illness phase-specific pharmacotherapy for schizophrenia. PMID- 26542741 TI - Spines, synapses, and schizophrenia. PMID- 26542742 TI - Understanding symbol coding in schizophrenia. PMID- 26542743 TI - Human epidermal growth factor receptor 2 testing in invasive breast cancer: should histological grade, type and oestrogen receptor status influence the decision to repeat testing? AB - AIMS: The recent American Society of Clinical Oncology/College of American Pathologists guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer recommend repeat testing based on tumour grade, tumour type, and hormone receptor status. The aim of this study was to test the value of these criteria. METHODS AND RESULTS: HER2 status was concordant in the core biopsies and excision specimens in 392 of 400 invasive carcinomas. The major reasons for discordance were amplification around the cut-off for positivity and tumour heterogeneity. Of 116 grade 3 carcinomas that were HER2-negative in the core biopsy, four were HER2-positive in the excision specimen. Three of these four either showed borderline negative amplification in the core biopsy or were heterogeneous. None of the 55 grade 1 carcinomas were HER2-positive. Review of repeat testing of HER2 in routine practice suggested that it may also be of value for multifocal tumours and if recommended by the person assessing the in-situ hybridization. CONCLUSIONS: Mandatory repeat HER2 testing of grade 3 HER2 negative carcinomas is not appropriate. This is particularly true if repeat testing is performed after borderline negative amplification in the core biopsy or in HER2-negative heterogeneous carcinomas. PMID- 26542744 TI - PI(4)P homeostasis: Who controls the controllers? AB - During recent decades, PI(4)P (phosphoinositol-4-phosphate) has been described as a key regulator of a wide range of cellular functions such as organelle biogenesis, lipid metabolism and distribution, membrane trafficking, ion channels, pumps, and transporter activities. In this review we will focus on the multiple mechanisms that regulate PI(4)P homeostasis ranging from those responsible for the spatial distribution of the PI4 kinases and PI(4)P phosphatase to those controlling their enzymatic activity or the delivery/presentation of the substrate, i.e. PI or PI(4)P, to the PI4Ks or PI(4)P phosphatase, respectively. We will also highlight the open questions in the field mainly dealing with the existence and mode of action of PI(4)P sensors that monitor its amount and can act as a rheostat tuning PI(4)P levels in different compartments and adapting them to the different needs of the cell. PMID- 26542745 TI - Targeted, noninvasive blockade of cortical neuronal activity. AB - Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies. PMID- 26542746 TI - Relationship between marijuana and other illicit drug use and depression/suicidal thoughts among late middle-aged and older adults. AB - BACKGROUND: Despite growing numbers of older-adult illicit drug users, research on this topic is rare. This study examined the relationship between marijuana and/or other illicit drug use and major depressive episode (MDE) and serious suicidal thoughts among those aged 50+ years in the USA. METHODS: The public use files of the 2008 to 2012 US National Survey on Drug Use and Health (NSDUH) provided data on 29,634 individuals aged 50+ years. Logistic regression analysis was used to test hypothesized associations between past-year marijuana and/or other illicit drug use and MDE and serious suicidal thoughts. RESULTS: Nearly 6% of the 50+ years age group reported past-year marijuana and/or other illicit drug use. Compared to non-users of any illicit drug, the odds of past-year MDE among those who used marijuana only, other illicit drugs only, and marijuana and other illicit drugs were 1.54 (95% CI = 1.17-2.03), 2.75 (95% CI = 1.75-4.33), and 2.12 (95% CI = 1.45-3.09), respectively. Those who used marijuana and other drugs also had higher odds (2.44, 95% CI = 1.58-3.77) of suicidal thoughts than non-users of any illicit drug. However, among users of any illicit drug, no difference was found among users of marijuana only, marijuana and other illicit drugs, and other illicit drugs only. Among marijuana users, marijuana use frequency was a significant correlate of suicidal thoughts only among those with MDE. CONCLUSIONS: Health and mental health (MH) service providers should pay close attention to the potential reciprocal effects of marijuana and other illicit drug use and MDE and suicidal thoughts among late middle-aged and older adults. PMID- 26542747 TI - On the Extraction of Charge Carrier Mobility in High-Mobility Organic Transistors. AB - Transistor parameter extraction by the conventional transconductance method can lead to a mobility overestimate. Organic transistors undergoing major contact resistance experience a significant drop in mobility upon mild annealing. Before annealing, strong field-dependent contact resistance yields nonlinear transfer curves with locally high transconductances, resulting in a mobility overestimate. After annealing, a contact resistance below 200 Omega cm is achieved, which is stable over a wide V(G) range. PMID- 26542748 TI - Energetic constraint of non-monotonic mass change during offspring growth: a general hypothesis and application of a new tool. AB - Post-natal growth is an important life-history trait and can be a sensitive indicator of ecological stress. For over 50 years, monotonic (never-decreasing) growth has been viewed as the predominant trajectory of post-natal mass change in most animal species, notably among birds. However, prevailing analytical approaches and energetic constraints may limit detection of non-monotonic (or multiphasic), determinate growth patterns, such as mass recession in birds (weight loss prior to fledging, preceded by overshooting adult mass), which is currently believed to be restricted to few taxa. Energetic surplus and shortfall are widespread conditions that can directly influence the degree of mass overshooting and recession. Thus, we hypothesize that in many species, prevailing energetic constraints force mass change away from a fundamental non-monotonic trajectory to instead follow a monotonic curve. We observed highly non-monotonic, mass change trajectories (overshooting adult mass by up to almost 20%) among common tern Sterna hirundo chicks, a well-studied species long-established as growing monotonically. We quantified the prevalence and magnitude of non monotonic mass change prior to fledging for 313 common tern chicks that successfully fledged from two discrete populations in multiple years. We used a new approach for analysing non-monotonic curves to examine differences in mass change trajectories between populations under contrasting abiotic (freshwater vs. saltwater) and biotic stresses (low rates of food provisioning). Some degree of mass recession occurred in 73% of all study chicks. Overshooting adult mass followed by extensive mass recession was most prevalent at our freshwater colony, being detected among 34-38% of chicks annually. Non-monotonic trajectories were less marked in populations experiencing ecological stress and among lower quality individuals. Chicks that were provisioned at higher rates were more likely to both overshoot adult mass and experience subsequent mass recession. Our results in common terns provide strong support for the hypothesis that non-monotonic trajectories are the fundamental pattern of mass change but are constrained to be monotonic under energetic shortfall. This justifies future tests of the generality of this hypothesis across a broad range of taxa. We also demonstrate a recent analytical tool that prevents routine fitting of monotonic curves without prior investigation of non-monotonic trends. PMID- 26542750 TI - Performance study of magnesium-sulfur battery using a graphene based sulfur composite cathode electrode and a non-nucleophilic Mg electrolyte. AB - Here we report for the first time the development of a Mg rechargeable battery using a graphene-sulfur nanocomposite as the cathode, a Mg-carbon composite as the anode and a non-nucleophilic Mg based complex in tetraglyme solvent as the electrolyte. The graphene-sulfur nanocomposites are prepared through a new pathway by the combination of thermal and chemical precipitation methods. The Mg/S cell delivers a higher reversible capacity (448 mA h g(-1)), a longer cyclability (236 mA h g(-1) at the end of the 50(th) cycle) and a better rate capability than previously described cells. The dissolution of Mg polysulfides to the anode side was studied by X-ray photoelectron spectroscopy. The use of a graphene-sulfur composite cathode electrode, with the properties of a high surface area, a porous morphology, a very good electronic conductivity and the presence of oxygen functional groups, along with a non-nucleophilic Mg electrolyte gives an improved battery performance. PMID- 26542749 TI - Stat3 is a candidate epigenetic biomarker of perinatal Bisphenol A exposure associated with murine hepatic tumors with implications for human health. AB - Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that has been implicated as a potential carcinogen and epigenotoxicant. We have previously reported dose-dependent incidence of hepatic tumors in 10-month-old isogenic mice perinatally exposed to BPA. Here, we evaluated DNA methylation at 3 candidate genes (Esr1, Il-6st, and Stat3) in liver tissue of BPA-exposed mice euthanized at 2 time points: post-natal day 22 (PND22; n = 147) or 10-months of age (n = 78, including n = 18 with hepatic tumors). Additionally, DNA methylation profiles were analyzed at human homologs of murine candidate genes in human fetal liver samples (n = 50) with known liver tissue BPA levels. Candidate genes were chosen based on reported expression changes in both rodent and human hepatocellular carcinoma (HCC). Regions for bisulfite sequencing were chosen by mining whole genome next generation sequencing methylation datasets of both mice and human liver samples with known perinatal BPA exposures. One of 3 candidate genes, Stat3, displayed dose-dependent DNA methylation changes in both 10-month mice with liver tumors as compared to those without liver tumors and 3-week sibling mice from the same exposure study, implicating Stat3 as a potential epigenetic biomarker of both early life BPA exposure and adult disease in mice. DNA methylation profiles within STAT3 varied with liver tissue BPA level in human fetal liver samples as well, suggesting STAT3 may be a translationally relevant candidate biomarker. These data implicate Stat3 as a potential early life biomarker of adult murine liver tumor risk following early BPA exposure with early evidence of relevance to human health. PMID- 26542751 TI - Functional polymorphisms in the gene encoding macrophage migration inhibitory factor (MIF) are associated with active pulmonary tuberculosis. AB - OBJECTIVE: The role of the cytokine, macrophage migration inhibition factor (MIF) was assessed in tuberculosis. This case-control study investigated whether commonly occurring functional MIF polymorphisms are associated with active tuberculosis as well as with serum levels of MIF, IFN-gamma and TNF-alpha. METHODS: Two MIF promoter polymorphisms, a functional -794 CATT5-8 microsatellite repeat (rs5844572) and a -173G/C single-nucleotide polymorphism (rs755622), were analysed by PCR and PCR-RFLP, respectively, in 47 patients and 50 healthy subjects. The mRNA level of MIF was performed by real-time PCR (RT-PCR), and MIF, IFN-gamma and TNF-alpha serum levels were determined by ELISA. RESULTS: A significant increase of MIF mRNA expression and MIF protein level were found in patients compared to healthy controls. Meanwhile, the increase of IFN-gamma and TNF-alpha serum levels were confirmed. According to the profile of genetic model, a significant association was found of genotypes carrying the -794 CATT 7 or 8 and -173 C risk alleles with susceptibility to active tuberculosis and with a significant increase of MIF, IFN-gamma and TNF-alpha. CONCLUSIONS: These data suggested a distinct genetic and immunopathogenic basis for tuberculosis at the MIF locus. Serum MIF, IFN-gamma and TNF-alpha profiles distinguish tuberculosis from the more inflammatory phenotype and may play a role in pathogenesis and as biomarkers of active tuberculosis. PMID- 26542752 TI - Nurse occupational burnout and patient-rated quality of care: The boundary conditions of emotional intelligence and demographic profiles. AB - AIM: Most previous studies on the relationship between occupational burnout and the quality of care among nurses have used self-reported data on the quality of care from nurses, thus rendering evaluating the relationship between burnout and the quality of care difficult. Hospitals increasingly hire contract nurses and high turnover rates remain a concern. Little is known about whether nurses' emotional intelligence and demographic factors such as contract status, tenure, and marital status affect the quality of care when burnout occurs. This study investigated the relationship between burnout and patient-rated quality of care and investigated the moderating role of emotional intelligence and demographic variables. METHODS: Hierarchical moderated regression was used to analyze 98 sets of paired data obtained from nurses and their patients at a teaching hospital in northern Taiwan. RESULTS: The results suggest that occupational burnout has a less unfavorable effect on the quality of care from permanent, married, and senior nurses. CONCLUSION: Nursing management should pay particular attention to retaining permanent, married, and senior nurses. To ensure a sustainable nursing workforce in the future, newly graduated registered nurses should have access to permanent positions and opportunities for long-term professional development. In addition, married nurses should be provided with flexible work-family arrangements to ensure their satisfaction in the nursing profession. PMID- 26542753 TI - A quantitative approach to analysing cortisol response in the horse. AB - The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 MUg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57 MUg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 MUg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test. PMID- 26542754 TI - Microbial immigration across the Mediterranean via airborne dust. AB - Dust particles lifting and discharge from Africa to Europe is a recurring phenomenon linked to air circulation conditions. The possibility that microorganisms are conveyed across distances entails important consequences in terms of biosafety and pathogens spread. Using culture independent DNA-based analyses via next generation sequencing of the 16 S genes from the airborne metagenome, the atmospheric microbial community was characterized and the hypothesis was tested that shifts in species diversity could be recorded in relation to dust discharge. As sampling ground the island of Sardinia was chosen, being an ideal cornerstone within the Mediterranean and a crossroad of wind circulation amidst Europe and Africa. Samples were collected in two opposite coastal sites and in two different weather conditions comparing dust-conveying winds from Africa with a control situation with winds from Europe. A major conserved core microbiome was evidenced but increases in species richness and presence of specific taxa were nevertheless observed in relation to each wind regime. Taxa which can feature strains with clinical implications were also detected. The approach is reported as a recommended model monitoring procedure for early warning alerts in frameworks of biosafety against natural spread of clinical microbiota across countries as well as to prevent bacteriological warfare. PMID- 26542755 TI - Beyond passivity: Dependency as a risk factor for intimate partner violence. AB - Interpersonal dependency in male perpetrators of intimate partner violence (IPV) is an understudied phenomenon but one that has noteworthy clinical implications. The present investigation used meta-analytic techniques to quantify the dependency-IPV link in all extant studies examining this relationship (n of studies = 17). Studies were gathered via an extensive literature search using relevant dependency/IPV search terms in the PsychInfo, Medline and Google Scholar databases. Results revealed a small but statistically significant relationship between dependency and perpetration of IPV in men (r = 0.150, Combined Z = 4.25, p < 0.0001), with the magnitude of the dependency-IPV link becoming stronger (r = 0.365, Combined Z = 6.00, p < 0.0001) when studies using measures of dependent personality disorder symptoms were omitted. Other moderators of the dependency IPV effect size included IPV measure, type of sample and perpetrator age. These findings illuminate the underlying dynamics and interpersonal processes involved in some instances of IPV and may aid in understanding how to identify and treat male perpetrators of domestic violence. PMID- 26542756 TI - Predictive or not predictive: understanding the mixed messages from the patient's DNA sequence. AB - AIMS AND OBJECTIVES: The aim of this discussion paper is to enable nurses to understand how deoxyribonucleic acid analysis can be predictive for some diseases and not predictive for others. This will facilitate nurses to interpret genomic test results and explain them to patients. BACKGROUND: Advances in technology mean that genetic testing is now commonly performed by sequencing the majority of an individual's genome or exome. This results in a huge amount of data, some of which can be used to predict or diagnose disease. DESIGN: This is a discussion paper. METHODS: This paper emerged from multiple discussions between the three authors over many months, culminating in a writing workshop to prepare this text. RESULTS: The results of DNA analysis can be used to diagnose or predict rare diseases that are caused by a mutation in a single gene. However, while there are a number of genetic factors that contribute to common diseases, the ability to predict whether an individual will develop that condition is limited by the overall heritability of the condition. Environmental factors (such as lifestyle) are likely to be more useful in predicting common disease than genomic testing. Genomic tests may be of use to inform management of diseases in specific situations. CONCLUSIONS: Genomic testing will be of use in diagnosing disorders due to single gene mutations, but the use of genomic testing to predict the chance of a patient being affected in the future by a common disease is unlikely to be a realistic option within a health service setting. RELEVANCE TO CLINICAL PRACTICE: Nurses will increasingly be involved in the use of genomic tests in mainstream patient care. However, they need to understand and be able to explain to patients the practical applications of and limitations of such tests. PMID- 26542757 TI - Epigenetic inactivation of TRAIL decoy receptors at 8p12-21.3 commonly deleted region confers sensitivity to Apo2L/trail-Cisplatin combination therapy in cervical cancer. AB - Multiple chromosomal regions are affected by deletions in cervical cancer (CC) genomes, but their consequence and target gene involvement remains unknown. Our single nucleotide polymorphism (SNP) array identified 8p copy number losses localized to an 8.4 Mb minimal deleted region (MDR) in 36% of CC. The 8p MDR was associated with tumor size, treatment outcome, and with multiple HPV infections. Genetic, epigenetic, and expression analyses of candidate genes at MDR identified promoter hypermethylation and/or inactivation of decoy receptors TNFRSF10C and TNFRSF10D in the majority of CC patients. TNFRSF10C methylation was also detected in precancerous lesions suggesting that this change is an early event in cervical tumorigenesis. We further demonstrate here that CC cell lines exhibiting downregulated expression of TNFRSF10C and/or TNFRSF10D effectively respond to TRAIL-induced apoptosis and this affect was synergistic in combination with DNA damaging chemotherapeutic drugs. We show that the CC cell lines harboring epigenetic inactivation of TRAIL decoy receptors effectively activate downstream caspases suggesting a critical role of inactivation of these genes in efficient execution of extrinsic apoptotic pathway and therapy response. Therefore, these findings shed new light on the role of genetic/epigenetic defects in TRAIL decoy receptor genes in the pathogenesis of CC and provide an opportunity to explore strategies to test decoy receptor gene inactivation as a biomarker of response to Apo2L/TRAIL-combination therapy. PMID- 26542758 TI - Flexible estimation of survival curves conditional on non-linear and time dependent predictor effects. AB - Prognostic studies often estimate survival curves for patients with different covariate vectors, but the validity of their results depends largely on the accuracy of the estimated covariate effects. To avoid conventional proportional hazards and linearity assumptions, flexible extensions of Cox's proportional hazards model incorporate non-linear (NL) and/or time-dependent (TD) covariate effects. However, their impact on survival curves estimation is unclear. Our primary goal is to develop and validate a flexible method for estimating individual patients' survival curves, conditional on multiple predictors with possibly NL and/or TD effects. We first obtain maximum partial likelihood estimates of NL and TD effects and use backward elimination to select statistically significant effects into a final multivariable model. We then plug the selected NL and TD estimates in the full likelihood function and estimate the baseline hazard function and the resulting survival curves, conditional on individual covariate vectors. The TD and NL functions and the log hazard are modeled with unpenalized regression B-splines. In simulations, our flexible survival curve estimates were unbiased and had much lower mean square errors than the conventional estimates. In real-life analyses of mortality after a septic shock, our model improved significantly the deviance (likelihood ratio test = 84.8, df = 20, p < 0.0001) and changed substantially the predicted survival for several subjects. PMID- 26542759 TI - Patterns of Somatic Diagnoses in Older People with Intellectual Disability: A Swedish Eleven Year Case-Control Study of Inpatient Data. AB - BACKGROUND: Knowledge about diagnoses patterns in older people with intellectual disabilities is limited. METHODS: The case group (n = 7936) comprised people with intellectual disabilities aged 55 years and older. The control group (n = 7936) was age matched and sex matched. Somatic inpatient diagnoses (2002-2012) were collected retrospectively. RESULTS: Several diagnoses were in several years significantly more common in the case group, particularly infections [odds ratio (OR) 1.78-4.08]; nervous system (OR 2.06-31.75); respiratory (OR 1.78-4.08) and genitourinary diseases (1.59-11.50); injuries, unspecified symptoms (OR 1.56 4.27); and external causes of morbidity (OR 1.53-4.08). The oldest in the case group had significantly less occurrence of tumours (OR 0.26-0.51), cardiovascular (OR 0.42-0.72), and musculoskeletal diseases (OR 0.32-0.53) than controls. CONCLUSIONS: Older people with intellectual disabilities have higher numbers of some diagnoses, but lower numbers of others. Further research on the reasons for the unique pattern of diagnoses in this group is required. PMID- 26542761 TI - Cost Analysis of Flexible Ureteroscope Repairs: Evaluation of 655 Procedures in a Community-Based Practice. AB - INTRODUCTION: The frequency of flexible ureteroscopy has increased with the introduction of improved instrumentation. Ureteroscopes allow increased endoscopic access to the ureter and kidney. However, maintenance and repair of scopes may increase the total procedure expense. METHODS: In 3 years (8/2011 7/2014), 655 flexible ureteroscopies were performed at a single-specialty, urology, ambulatory surgery center. Procedures were performed by 26 board certified urologists using four Olympus URF P5 flexible ureteroscopes. The instruments were handled by a single team and sterilized through the STERIS System E1. Repairs were performed by the manufacturer on an as needed basis. Patient records were reviewed to determine the preoperative diagnosis, operative time, location and size of the stone, and use of laser or ureteral sheath. The occurrence, nature of flexible ureteroscope damage, and cost of repairs were evaluated. RESULTS: Of the ureteroscopies performed, 78% was for the treatment of calculi (50.1% in the kidney). Mean stone size was 8.5 +/- 0.2 mm, with larger stones (11 mm) located in the kidney. The flexible ureteroscope was advanced over a guidewire (88% of cases); a laser fiber was introduced in 70%, and a ureteral sheath was used in 13.4%. Mean procedure time was 40 minutes. The most common reasons for ureteroscope repair were cloudy lens (16 repairs) and broken optic fibers (9 repairs). There were 31 repairs during the study period (average 21 cases per repair). Flexible ureteroscopes were out of service for an average of 11 days per repair (range 3-20). The total cost of repairs was $233,150 or ~$7521 per repair. The average repair cost per flexible ureteroscopy performed was $355. CONCLUSIONS: Expenses associated with instrument repair can significantly impact a procedure's net revenue, thus efforts should be made to minimize instrument breakage. The expense of repairing a flexible ureteroscope per procedure can be significant and needs to be considered when pricing this procedure. PMID- 26542760 TI - Apelin regulates FoxO3 translocation to mediate cardioprotective responses to myocardial injury and obesity. AB - The increasing incidence of obesity accentuates the importance of identifying mechanisms and optimal therapeutic strategies for patients with heart failure (HF) in relation to obesity status. Here, we investigated the association between plasma level of apelin, an adipocyte-derived factor, and clinicopathological features of obese and non-obese patients with HF. We further explored potential regulatory mechanisms of cardiac cell fate responses in conditions combining myocardial injury and obesity. In a prospective, cross-sectional study involving patients with HF we show that obese patients (BMI >= 30 kg/m(2)) have higher left ventricular ejection fraction (LVEF) and greater levels of plasma apelin (p < 0.005) than non-obese patients (< 30 kg/m(2)), independently of ischemic etiology. In a mouse model combining ischemia-reperfusion (I/R) injury and high fat diet (HFD)-induced obesity, we identify apelin as a novel regulator of FoxO3 trafficking in cardiomyocytes. Confocal microscopy analysis of cardiac cells revealed that apelin prevents nuclear translocation of FoxO3 in response to oxygen deprivation through a PI3K pathway. These findings uncover apelin as a novel regulator of FoxO3 nucleocytoplasmic trafficking in cardiac cells in response to stress and provide insight into its potential clinical relevance in obese patients with HF. PMID- 26542762 TI - In vitro selection of RNA aptamers against CA125 tumor marker in ovarian cancer and its study by optical biosensing. AB - Early identification of neoplastic diseases is essential to achieve timely therapeutic interventions and significantly reduce the mortality of patients. A well-known biomarker is the Cancer Antigen 125 (CA125) or 16 mucin (MUC 16), a glycoprotein of the human family of mucins, already used for the diagnostic and prognostic evaluation of ovarian cancer. Therefore, the detection of CA125 to now remains a promising tool in the early diagnosis of this tumor. In this paper, we describe the development of RNA aptamers that bind with high affinity the tumor antigen CA125. We performed eight cycles of selection against CA125 purified protein. The selected aptamers were cloned and sequenced and the binding properties of the most promising sequences were studied by Real Time PCR and Surface Plasmon Resonance (SPR) to evaluate their ability in targeting CA125 protein with perspective applications in aptamer-based bioassays. PMID- 26542763 TI - Visual detection of Flavivirus RNA in living cells. AB - Flaviviruses include a wide range of important human pathogens delivered by insects or ticks. These viruses have a positive-stranded RNA genome that is replicated in the cytoplasm of the infected cell. The viral RNA genome is the template for transcription by the virally encoded RNA polymerase and for translation of the viral proteins. Furthermore, the double-stranded RNA intermediates of viral replication are believed to trigger the innate immune response through interaction with cytoplasmic cellular sensors. Therefore, understanding the subcellular distribution and dynamics of Flavivirus RNAs is of paramount importance to understand the interaction of the virus with its cellular host, which could be of insect, tick or mammalian, including human, origin. Recent advances on the visualization of Flavivirus RNA in living cells together with the development of methods to measure the dynamic properties of viral RNA are reviewed and discussed in this essay. In particular the application of bleaching techniques such as fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) are analysed in the context of tick-borne encephalitis virus replication. Conclusions driven by this approached are discussed in the wider context Flavivirus infection. PMID- 26542765 TI - Endoscopic sphincterotomy and cholecystectomy in acute biliary pancreatitis. AB - BACKGROUND: This review discusses current insights with regard to biliary tract management during and after acute biliary pancreatitis. METHODS: A MEDLINE and EMBASE search was done and studies were selected based on methodological quality and publication date. The recommendations of recent guidelines are incorporated in this review. In absence of consensus in the literature, expert opinion is expressed. RESULTS: There is no role for early endoscopic retrograde cholangiopancreatography (ERCP) in patients with (predicted) mild biliary pancreatitis to improve outcome. In case of persisting choledocholithiasis, ERCP with stone extraction is scheduled electively when the acute event has subsided. Whether early ERCP with sphincterotomy is beneficial in patients with predicted severe pancreatitis remains subject to debate. Regardless of disease severity, in case of concomitant cholangitis urgent endoscopic sphincterotomy (ES) is recommended. As a definitive treatment to reduce the risk of recurrent biliary events in the long term, ES is inferior to cholecystectomy and should be reserved for patients considered unfit for surgery. After severe biliary pancreatitis, cholecystectomy should be postponed until all signs of inflammation have subsided. In patients with mild pancreatitis, cholecystectomy during the primary admission reduces the risk of recurrent biliary complications. CONCLUSION: Recent research has provided valuable data to guide biliary tract management in the setting of acute biliary pancreatitis with great value and benefit for patients and clinicians. Some important clinical dilemmas remain, but it is anticipated that on-going clinical trials will deliver some important insights and additional guidance soon. PMID- 26542764 TI - A high risk of osteosarcoma in individuals who are homozygous for the p.D104N in endostatin. AB - The D104N polymorphism (p.D104N) in endostatin has been previously identified in many types of cancer, and this polymorphism is believed to be a phenotypic modulator in some tumors. However, it is unknown whether endostatin p.D104N affects the risk and progression of osteosarcoma (OS). Here, we analyzed the p.D104N endostatin variant in 236 patients with OS and 418 healthy individuals. Similar frequencies of wild type and heterozygous p.104DN endostatin were observed in controls and OS patients. Interestingly, the frequency of the homozygous p.D104N (p.104NN) genotype was higher in OS patients group compared to control group, suggesting that individuals with p.104NN endostatin have a significantly increased risk for OS. In addition, OS patients with p.104NN endostatin had a shorter survival time and a higher rate of metastasis than OS patients with wild type endostatin. Animal experiments revealed that overexpression of p.104NN endostatin did not significantly inhibit OS lung metastasis. Interestingly, administration of endostatin dramatically inhibited OS lung metastasis in the p.104NN endostatin xenograft model. Together, these results suggest that p.104NN of endostatin is associated with the risk of OS and demonstrates predictive significance for clinical outcome in OS patients. In addition, endostatin therapy may be necessary for OS patients harboring p.104NN endostatin. PMID- 26542766 TI - Ce-Zr-La/Al2O3 prepared in a continuous stirred-tank reactor: a highly thermostable support for an efficient Rh-based three-way catalyst. AB - Two Ce-Zr-La/Al2O3 composite oxides, CZLA-C and CZLA-B, were synthesized using a co-precipitation method in a continuous stirred-tank reactor (CSTR) and a batch reactor (BR), respectively. Two Rh-based three-way catalysts (TWCs), Rh/CZLA-C and Rh/CZLA-B were obtained by a wet-impregnation method using the two composites as the supports. The physicochemical properties of the samples before and after thermal treatment at 1000 degrees C were characterized by N2 adsorption desorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), H2-temperature programmed reduction (H2-TPR) and CO chemisorption. The results indicated that CZLA-C shows higher thermal stability than CZLA-B due to a sparsely-agglomerated morphology. Compared with Rh/CZLA-B, Rh/CZLA-C displayed better reducibility and higher thermal stability and exhibited significantly higher activity in the catalytic removal of the simulated gasoline vehicle exhaust emission (NO, CO and C3H8). Our work can provide a facile and economical synthesis route to advanced support materials and catalysts for exhaust emission control. PMID- 26542768 TI - Discussion. PMID- 26542769 TI - Analysis of Nitrosamines in Cooked Bacon by QuEChERS Sample Preparation and Gas Chromatography-Tandem Mass Spectrometry with Backflushing. AB - Nitrites are added as a preservative to a variety of cured meats, including bacon, to kill bacteria, extend shelf life, and improve quality. During cooking, nitrites in the meat can be converted to carcinogenic nitrosamines (NAs), the formation of which is mitigated by the addition of antioxidants. In the past, the U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) monitored NAs in pan-fried bacon, but FSIS terminated monitoring of NAs in the 1990s due to the very low levels found. FSIS recently chose to conduct a risk assessment of NAs in cooked bacon to determine if current levels warrant routine monitoring of NAs again. To meet FSIS needs, we developed, validated, and implemented a new method of sample preparation and analysis to test cooked bacon for five NAs of most concern, which consist of N-nitroso-dimethylamine, diethylamine, -dibutylamine, -piperidine, and -pyrrolidine. Sample preparation was based on the QuEChERS (quick, easy, cheap, effective, rugged, and safe) approach and analysis by gas chromatography-tandem mass spectrometry. Ruggedness was improved markedly in the analysis of the complex fatty extracts by backflushing the guard column, injection liner, and half of the analytical column after every injection. Validation results were acceptable with recoveries of 70 120% and <20% RSDs for the five NAs, with a reporting limit of 0.1 ng/g. NA concentrations in 48 samples were all <15 ng/g, with most <1 ng/g and many <0.1 ng/g. Also, microwave cooking of bacon gave slightly lower concentrations overall compared to pan-frying. PMID- 26542767 TI - Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. AB - BACKGROUND: Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion. METHODS: Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers. RESULTS: WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients beta-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively. CONCLUSION: KU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo. PMID- 26542770 TI - Mutational and phenotypical spectrum of phenylalanine hydroxylase deficiency in Denmark. AB - We describe the genotypes of the complete cohort, from 1967 to 2014, of phenylketonuria (PKU) patients in Denmark, in total 376 patients. A total of 752 independent alleles were investigated. Mutations were identified on 744 PKU alleles (98.9%). In total, 82 different mutations were present in the cohort. The most frequent mutation c.1315+1G>A (IVS12+1G>A) was found on 25.80% of the 744 alleles. Other very frequent mutations were c.1222C>T (p.R408W) (16.93%) and c.1241A>G (p.Y414C) (11.15%). Among the identified mutations, five mutations; c.532G>A (p.E178K), c.730C>T (p.P244S), c.925G>A (p.A309T), c.1228T>A (p.F410I), and c.1199+4A>G (IVS11+4A>G) have not been reported previously. The metabolic phenotypes of PKU are classified into four categories; 'classical PKU', 'moderate PKU', 'mild PKU' and 'mild hyperphenylalaninemia'. In this study, we assigned the phenotypic outcome of three of the five novel mutations and furthermore six not previously classified mutations to one of the four PKU categories. PMID- 26542771 TI - [Vaginal reflux: What is not known cannot be diagnosed]. PMID- 26542772 TI - [Facial haemangioma as a diagnostic key of PHACES]. PMID- 26542773 TI - [Assessment of foetal nutrition status at birth using the CANS score]. AB - INTRODUCTION: Foetal malnutrition (FM) is the result of a loss or failure of intrauterine acquisition of the correct amount of fat and muscle mass, with short and long term implications. As the diagnosis of FM is essentially clinical, the aim of this study is to detect the incidence of FM using the Clinical Assessment of Nutritional Status (CANS) score, and compare the results with the classic anthropometric parameters. PATIENTS AND METHODS: Retrospective population of term infants was studied between 2003 and 2014 (n=14,477). They were classified into adequate weight (AGA), small weight (SGA) and large weight (LGA) for gestational age newborns. The CANS score was performed on all infants enrolled in the study, and the ponderal index (PI) was calculated, considering an FM cut off value of a CANS score <25 and PI <2.2g/cm(3). RESULTS: Using the CANS score, 7.6% (n 1,101) of the population showed FM, 50.3% (n=538) of SGA, 76.2% (n=193) subgroup =2.2g/cm(3) (n=14.356), and the CANS score was >24 in 49% with PI <2.2g/cm(3) (n=109) CONCLUSIONS: It is worthwhile identifying all newborns with FM due to the risks they may have in the short and long term. CANS score assessment allows a better identification of nutritional status of infants than only using the curves of weight for gestational age. PMID- 26542774 TI - Serum concentrations of kynurenines in adult patients with attention-deficit hyperactivity disorder (ADHD): a case-control study. AB - BACKGROUND: The essential amino acid tryptophan is catabolised mainly through the kynurenine pathway. Altered circulating levels of kynurenines have been reported in chronic inflammatory conditions and in several neuropsychiatric disorders, including depression and schizophrenia. Candidate gene studies suggest that genes related to the kynurenine catabolism may be associated with attention-deficit hyperactivity disorder (ADHD). Additionally, ADHD patients often report comorbid depression or anxiety. In this study we investigated serum levels of kynurenines in Norwegian adult ADHD patients and adult controls. METHODS: We compared serum levels of tryptophan and the seven tryptophan metabolites kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3 hydroxyanthranilic acid and quinolinic acid in 133 adult patients with ADHD and 131 adult controls (18-40 years). Riboflavin (vitamin B2), total vitamin B6 and the nicotine metabolite cotinine were also measured. Serum samples were analysed using mass spectrometry. Patients and controls reported comorbid disorders and past (childhood) and current ADHD symptoms using the Wender Utah Rating Scale (WURS) and the Adult ADHD Self-report Scale (ASRS). Logistic regression was used to calculate odds ratios for having an ADHD diagnosis for different serum levels of each metabolite. In addition, we used Spearman's correlation analysis to investigate the correlation between serum levels of tryptophan and kynurenines and ADHD symptom scores. RESULTS: Lower serum concentrations of tryptophan [odds ratio 0.61 (95 % confidence interval 0.45-0.83)], kynurenic acid [0.73 (0.53 0.99)], xanthurenic acid [0.65 (0.48-0.89)] and 3-hydroxyanthranilic acid [0.63 (0.46-0.85)], and higher levels of cotinine [7.17 (4.37-12.58)], were significantly associated with ADHD. After adjusting for tryptophan levels, only 3 hydroxyanthranilic acid and cotinine remained significant. Lower levels of tryptophan and kynurenine were also found to be correlated with higher total ASRS score and higher total WURS score, when adjusting for smoking and age. CONCLUSIONS: Our results suggest that there may be differences in serum levels of tryptophan and kynurenines between adult ADHD patients and adult controls. Although our findings do not suggest a chronic immune activation in ADHD, the underlying mechanisms and possible clinical implications of the differences should be further explored. PMID- 26542775 TI - Enantioselective Rh(I)-Catalyzed Addition of Arylboronic Acids to Cyclic Ketimines. AB - A method for the enantioselective synthesis of chiral alpha-tertiary amines via Rh-catalyzed 1,2-addition of arylboronic acids to cyclic ketimines is described. The products are efficiently accessed in good yields and excellent enantioselectivities using a commercially available chiral ligand. The reaction scope includes vinyl, aryl, and heteroarylboronic acids with yields ranging from 40% to 99% and enantiomeric excesses from 88% to 99%. Conversion of an addition product into an alpha,alpha-diaryl-substituted amino acid is also demonstrated. PMID- 26542776 TI - Excessive reactive oxygen species are therapeutic targets for intervertebral disc degeneration. AB - INTRODUCTION: Oxidative stress has been reported to be involved in numerous human diseases, including musculoskeletal disorders such as osteoarthritis. However, the interaction between intervertebral disc (IVD) degeneration and oxidative stress is not well understood. The purpose of the present study was to elucidate the contribution of oxidative stress to IVD degeneration and the efficacy of antioxidant treatment for degenerative discs. METHODS: The expression level of an oxidative stress marker, nitrotyrosine, was assessed by immunohistochemistry and Western blotting. For evaluating intracellular reactive oxygen species (ROS) levels and oxidative stress in rat annulus fibrosus (AF) cells, flow cytometry and luciferase assay with an OKD48 construct were performed. The grade of IVD degeneration was assessed by magnetic resonance imaging and histological analysis. RESULTS: A high frequency of nitrotyrosine-positive cells was observed in rat and human degenerative discs. mRNA expression of catabolic factors such as tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), and cyclooxygenase-2 (COX-2) was significantly induced by treatment with H2O2 or buthionine sulfoximine, whereas that of aggrecan, an important chondrogenic proteoglycan, was reduced in a dose-dependent manner. Treatment with mitogen activated protein kinase (MAPK) inhibitors blocked the inductive effect of excessive ROS on COX-2 mRNA expression. Western blotting confirmed the phosphorylation of MAPKs in H2O2 and BSO-treated AF cells. Conversely, we showed that TNF-alpha induced oxidative stress with increased intracellular ROS levels in AF cells. Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated the catabolic effect of excessive ROS and TNF-alpha in vitro. Finally, we showed that oral administration of NAC prevented IVD degeneration in rat degenerative model. CONCLUSIONS: A positive feedback loop was formed between excessive ROS and TNF alpha in AF cells. Thus, oxidative stress contributes to the progression of IVD degeneration and NAC can be a therapeutic option for IVD degeneration. PMID- 26542777 TI - Population-based prevalence of malaria among pregnant women in Enugu State, Nigeria: the Healthy Beginning Initiative. AB - BACKGROUND: Malaria adversely affects pregnant women and their fetuses or neonates. Estimates of the malaria burden in pregnant women based on health facilities often do not present a true picture of the problem due to the low proportion of women delivering at these facilities in malaria-endemic regions. METHODS: Data for this study were obtained from the Healthy Beginning Initiative using community-based sampling. Self-identified pregnant women between the ages of 17-45 years were recruited from churches in Enugu State, Nigeria. Malaria parasitaemia was classified as high and low based on the malaria plus system. RESULTS: Of the 2069 pregnant women for whom malaria parasitaemia levels were recorded, over 99 % tested positive for malaria parasitaemia, 62 % showed low parasitaemia and 38 % high parasitaemia. After controlling for confounding variables, odds for high parasitaemia were lower among those who had more people in the household (for every one person increase in a household, OR = 0.94, 95 % CI 0.89-0.99). CONCLUSION: Results of this study are consistent with hospital based estimates of malaria during pregnancy in southeastern Nigeria. Based on the high prevalence of malaria parasitaemia in this sample, education on best practices to prevent malaria during pregnancy, and resources in support of these practices are urgently needed. PMID- 26542778 TI - HDAC3 role in medication consumption in medication overuse headache patients: a pilot study. AB - BACKGROUND: Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. HDAC3 is inhibited by sodium valproate, a drug with proven efficacy in MOH. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse. RESULTS: In this association study, we sequenced all exons, intron/exon junctions, and 3' 5'UTR regions of HDAC3 in 23 MOH patients to investigate its role in medication overuse. Associations between genotypes with continuous and dichotomous clinical characteristics were tested by multivariate analysis and Fisher's exact test, respectively. Sequencing of HDAC3 revealed six single-nucleotide polymorphisms. The G allele of rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which medications were used (p = 0.006 and p = 0.007, respectively), but neither with headache frequency or intensity. None of the single-nucleotide polymorphisms (SNPs) was associated with clinical characteristics or response to sodium valproate. CONCLUSIONS: HDAC3 could be implicated in excessive medication consumption in MOH patients. Our preliminary findings provide support for the need of further investigation on larger independent samples to confirm and extend the role of HDAC3 in medication overuse headache. PMID- 26542779 TI - Outcome of vulvar reconstruction in patients with advanced and recurrent vulvar malignancies. AB - BACKGROUND: The use of flaps in vulvar cancer-related reconstruction has been increasing, but few studies have evaluated the outcome and quality of life of patients after this surgery. The purpose of this study was to evaluate the outcomes of vulvar reconstruction using musculocutaneous/skin flaps in patients with advanced and recurrent vulvar malignancies. METHODS: Patients with vulvar malignancies who underwent vulvar reconstruction using different types of flaps were retrospectively reviewed. Patient outcomes were evaluated with a focus on quality of life and prognosis. RESULTS: Thirty-six patients were enrolled, 58.33% of them used anterolateral thigh flap (ALT), 16.67% of them used pudendal thigh flap (PTF), 11.11% of them used deep omferior epigastric perforator (DIEP) and gracilis myocutaneous flap were used in 2.78% of the patients, the other 11.11% patients used two types of flaps. Eleven patients (30.56%) developed complications, including 5 patients (13.89%) with partial necrosis, 5 (13.89%) with minimal wound dehiscence and 1 (2.78%) with flap cellulitis. All patients who developed partial necrosis (13.89%) underwent reoperation. The mean verbal rating scale score was 1.44 before reconstruction and 0.17 after surgery (P < 0.0001). The mean performance status was 1.67 before surgery and improved to 0.31 after surgery (P < 0.0001). The median overall follow-up time after vulvar reconstruction was 9 months. Twenty-one patients (58.3%) developed recurrence at a median interval of 5 months after vulvar reconstruction. After a median follow up time of 14 months, 41.7 % of the patients were living and disease-free. The 5 year survival of the 36 patients was 53.8%. CONCLUSION: Soft tissue reconstruction in patients undergoing resection of advanced/recurrent vulvar malignances is associated with a low rate of postoperative complications, decreased pain, and improved functional status. Although the recurrence rate in this patient population is high, a reasonable proportion of patients who undergo resection for advanced/recurrent vulvar cancer and reconstructive surgery appear to benefit. PMID- 26542780 TI - Pediatric heart transplant for unresectable primary cardiac tumor. AB - Surgery for primary cardiac tumors in children includes complete resection, partial resection, and cardiac transplantation. A pediatric heart transplant in this setting is associated with significantly higher mortality and poorer long term outcome, and it is reserved for unresectable tumors. We recently performed an emergency pediatric heart transplant in a 7-year-old boy with an unresectable cardiac fibroma in the left ventricle. PMID- 26542781 TI - Prediction of lung tumor palpability using high-resolution computed tomography. AB - BACKGROUND: Palpation is the most important means of locating lung tumors and resecting them with sufficient margins. This study aimed to predict the palpability of pulmonary lesions using high-resolution computed tomography. METHODS: Eighty-six pulmonary lesions were palpated in fresh resected lung specimens from July 2013 to March 2014. The following parameters were compared between 10 impalpable and 76 palpable lesions: maximum tumor size in pulmonary and bone window level settings, consolidation tumor size in pulmonary window level setting, and pleural-tumor distance. In 54 adenocarcinomas, the lepidic component and fibrosis foci rates were compared between the two groups. RESULTS: Tumor size in bone window level setting and the consolidation tumor size were significantly smaller in the impalpable group (both p < 0.001), and an operational cutoff of 5 mm was identified by receiver-operating characteristic analysis (sensitivity/specificity was 90.0%/94.7% and 90.0%/86.9%, respectively). Pulmonary lesions were impalpable with 87.5% probability when the tumor size in bone window level setting was <= 5 mm and the pleural-tumor distance was >= 5 mm, and with 85.7% probability when the consolidation tumor size was <= 5 mm and the pleural-tumor distance was >= 5 mm. Lepidic component and fibrosis foci rates of impalpable/palpable lesions were 96.0%/52.8% and 4.0%/24.7%, respectively (both p < 0.001). CONCLUSIONS: Tumor size in bone window level setting or a consolidation tumor size <= 5 mm and pleural-tumor distance >= 5 mm are simple criteria that are potentially useful indicators for preoperative marking to locate small-sized lepidic-predominant adenocarcinomas with few fibrotic foci. PMID- 26542782 TI - Cardiac perforation caused by cement after percutaneous balloon kyphoplasty. AB - Percutaneous balloon kyphoplasty is a relatively simple, convenient, and minimally invasive procedure in which polymethylmethacrylate bone cement is used to manage back pain and spinal instability associated with osteoporotic compression fractures and other osteolytic spinal lesions. However, cement leakage into the venous system is a serious complication following percutaneous balloon kyphoplasty. A 74-year-old woman presented with cardiac perforation and pulmonary embolism caused by cement leakage into her venous system. She subsequently underwent surgery to effectively remove a needle-shaped cement piece from the right ventricular wall, without cardiopulmonary bypass and cardiac arrest. PMID- 26542783 TI - Staged repair of hemitruncus without prosthetic material. AB - Right pulmonary artery banding was performed in a patient with right hemitruncus at 17 days of age, due to severe hypertension in both pulmonary arteries and severely reduced right ventricular contraction. Following the procedure, the pulmonary hypertension and right ventricular contraction gradually improved with pulmonary vasodilator administration, and total correction was achieved two months later. A cardiac catheter examination at the 1-year follow-up showed normal pressure in both pulmonary arteries and good right ventricular contraction. PMID- 26542784 TI - Pseudoaneurysm fistulized into pulmonary artery 13 years after aortic surgery. AB - Pseudoaneurysm formation some years after aortic root or ascending aorta surgery, complicated by fistula formation through a branch of the pulmonary artery, is a rare condition described only in case reports. We describe a case of this rare complication in a 58-year-old man, which occurred 13 years after aortic surgery and was characterized by a huge pseudoaneurysm of 70 mm that fistulized into the right pulmonary artery, causing a life-threatening situation. PMID- 26542785 TI - Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients. AB - Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials. PMID- 26542786 TI - Examination of the torque required to passively palmar abduct the thumb CMC joint in a pediatric population with hemiplegia and stroke. AB - Many activities of daily living involve precision grasping and bimanual manipulation, such as putting toothpaste on a toothbrush or feeding oneself. However, children afflicted by stroke, cerebral palsy, or traumatic brain injury may have lost or never had the ability to actively and accurately control the thumb. To translate insights from adult rehabilitation robotics to innovative therapies for hand rehabilitation in pediatric care, specifically for thumb deformities, an understanding of the torque needed to abduct the thumb to assist grasping tasks is required. Participants (n=16, 10 female, 13.2+/-3.1 years) had an upper extremity evaluation and measures were made of their passive range of motion, anthropometrics, and torques to abduct the thumb for both their affected and non-affected sides. Torque measures were made using a custom wrist orthosis that was adjusted for each participant. The torque to achieve maximum abduction was 1.47+/-0.61inlb for the non-affected side and 1.51+/-0.68inlb for the affected side, with a maximum recorded value of 4.87inlb. The overall maximum applied torque was observed during adduction and was 5.10inlb. We saw variation in the applied torque, which could have been due to the applied torques by the Occupational Therapist or the participant actively assisting or resisting the motion rather than remaining passive. We expect similar muscle and participant variation to exist with an assistive device. Thus, the data presented here can be used to inform the specifications for the development of an assistive thumb orthosis for children with "thumb-in-palm" deformity. PMID- 26542787 TI - The influence of bone density and anisotropy in finite element models of distal radius fracture osteosynthesis: Evaluations and comparison to experiments. AB - Continuum-level finite element (FE) models can be used to analyze and improve osteosynthesis procedures for distal radius fractures (DRF) from a biomechanical point of view. However, previous models oversimplified the bone material and lacked thorough experimental validation. The goal of this study was to assess the influence of local bone density and anisotropy in FE models of DRF osteosynthesis for predictions of axial stiffness, implant plate stresses, and screw loads. Experiments and FE analysis were conducted in 25 fresh frozen cadaveric radii with DRFs treated by volar locking plate osteosynthesis. Specimen specific geometries were captured using clinical quantitative CT (QCT) scans of the prepared samples. Local bone material properties were computed based on high resolution CT (HR-pQCT) scans of the intact radii. The axial stiffness and individual screw loads were evaluated in FE models, with (1) orthotropic inhomogeneous (OrthoInhom), (2) isotropic inhomogeneous (IsoInhom), and (3) isotropic homogeneous (IsoHom) bone material and compared to the experimental axial stiffness and screw-plate interface failures. FE simulated and experimental axial stiffness correlated significantly (p<0.0001) for all three model types. The coefficient of determination was similar for OrthoInhom (R(2)=0.807) and IsoInhom (R(2)=0.816) models but considerably lower for IsoHom models (R(2)=0.500). The peak screw loads were in qualitative agreement with experimental screw-plate interface failure. Individual loads and implant plate stresses of IsoHom models differed significantly (p<0.05) from OrthoInhom and IsoInhom models. In conclusion, including local bone density in FE models of DRF osteosynthesis is essential whereas local bone anisotropy hardly effects the models' predictive abilities. PMID- 26542788 TI - The effect of mechanical strains in soft tissues of the shoulder during load carriage. AB - Soldiers and recreational backpackers are often required to carry heavy loads during military operations or hiking. Shoulder strain appears to be one of the limiting factors of load carriage due to skin and underlying soft tissue deformations, trapped nerves, or obstruction of blood vessels. The present study was aimed to determine relationships between backpack weights and the state of loads in the shoulder's inner tissues, with a special focus on the deformations in the brachial plexus. Open-MRI scans were used for developing and then verifying a three-dimensional, non-linear, large deformation, finite element model of the shoulder. Loads were applied at the strap-shoulder contact surfaces of the model by pulling the strap towards the shoulder until the desired load was reached. Increasing the strap tensile forces up to a load that represents 35kg backpack resulted in gradual increase in strains within the underlying soft tissues: the maximal tensile strain in the brachial plexus for a 25kg backpack was 12%, and while carrying 35kg, the maximal tensile strain increased to 16%. The lateral aspect of the brachial plexus was found to be more vulnerable to deformation-inflicted effects than the medial aspect. This is due to the anatomy of the clavicle that poorly shields the plexus from compressive loads applied during load carriage, while the neural tissue in the medial aspect of the shoulder is better protected by the clavicle. The newly developed model can serve as a tool to estimate soft tissue deformations in the brachial plexus for heavy backpack loads, up to 35kg. This method will allow further development of new strap structures and materials for alleviating the strains applied on the shoulder soft tissues. PMID- 26542789 TI - [The patents game. Generic and biosimilar drugs]. AB - The protection provided by patents on medicines has a limited duration. The expiry of patents expiration allows copies of the drugs to be released, competing with original. At first, they were identical to the original, known as generic drugs, but in recent years, due to the marketing of biological therapies and the expiry of many of their patents, biosimilar drugs have also emerged. These are not exact copies of the original, but, like generic drugs, biosimilar drugs have to demonstrate equivalence to the reference drugs in quality, safety and efficacy. Nevertheless, despite their importance and contribution to sustainability of health system, doctors are sometimes unaware of differences between them, and their impact in terms of clinical and economic effects. An attempt is made to review and clarify certain aspects often unknown by physicians, despite their involvement in their use. PMID- 26542790 TI - [Verification of compliance with specifications of analytical quality]. PMID- 26542791 TI - [Patient identification errors and biological samples in the analytical process: Is it possible to improve patient safety?]. AB - BACKGROUND: Patient identification errors and biological samples are one of the problems with the highest risk factor in causing an adverse event in the patient. OBJECTIVE: To detect and analyse the causes of patient identification errors in analytical requests (PIEAR) from emergency departments, and to develop improvement strategies. MATERIAL AND METHODS: A process and protocol was designed, to be followed by all professionals involved in the requesting and performing of laboratory tests. Evaluation and monitoring indicators of PIEAR were determined, before and after the implementation of these improvement measures (years 2010-2014). RESULTS: A total of 316 PIEAR were detected in a total of 483,254 emergency service requests during the study period, representing a mean of 6.80/10,000 requests. Patient identification failure was the most frequent in all the 6-monthly periods assessed, with a significant difference (P<.0001). CONCLUSIONS: The improvement strategies applied showed to be effective in detecting PIEAR, as well as the prevention of such errors. However, we must continue working with this strategy, promoting a culture of safety for all the professionals involved, and trying to achieve the goal that 100% of the analytical and samples are properly identified. PMID- 26542792 TI - Optimizing citrate dose for regional anticoagulation in continuous renal replacement therapy: measuring citrate concentrations instead of ionized calcium? PMID- 26542793 TI - ST depression in lead aVL differentiates inferior ST-elevation myocardial infarction from pericarditis. AB - BACKGROUND: ST-segment elevation (STE) due to inferior STE myocardial infarction (STEMI) may be misdiagnosed as pericarditis. Conversely, this less life threatening etiology of ST elevation may be confused for inferior STEMI. We sought to determine if the presence of any ST-segment depression in lead aVL would differentiate inferior STEMI from pericarditis. METHODS: Retrospective study of 3 populations. Cohort 1 included patients coded as inferior STEMI, cohort 2 included patients with a discharge diagnosis of pericarditis who presented with chest pain and at least 0.5 mm of ST elevation in at least 1 inferior lead. We analyzed the presenting electrocardiogram in both populations, with careful assessment of leads II, III, aVF, and aVL. In addition, we retrospectively studied a third cohort of patients with subtle inferior STEMI (<1 mm STE with occluded artery on catheterization) and assessed the sensitivity of ST depression in lead aVL for this group. RESULTS: Of 154 inferior STEMI patients, 154 had some amount of ST depression in lead aVL (100%; confidence interval, 98%-100%). Of the 49 electrocardiograms in the pericarditis group, all 49 had some inferior STE but none had any ST-segment depression in lead aVL (specificity, 100%; confidence interval, 91%-100%). In the third cohort, there were 272 inferior MIs with coronary occlusion, of which 54 were "subtle." Of these, 49 had some ST depression in lead aVL. CONCLUSION: When there is inferior ST-segment elevation, the presence of any ST depression in lead aVL is highly sensitive for coronary occlusion in inferior myocardial infarction and very specific for differentiating inferior myocardial infarction from pericarditis. PMID- 26542794 TI - Cardiovascular disease outcomes in tertiary care centers in Japan. PMID- 26542795 TI - Appropriateness of epinephrine use in ED patients with anaphylaxis. AB - BACKGROUND: Studies have demonstrated low rates of emergency department (ED) epinephrine administration for anaphylaxis patients, suggestive of ED undertreatment of anaphylaxis. Our study assessed the appropriateness of ED epinephrine administration in anaphylaxis management. METHODS: A prospective observational study was conducted involving ED patients presenting with possible allergic reactions. Patients and ED providers completed questionnaires regarding the suspected trigger, signs and symptoms, and prehospital treatment. Two board certified allergists-immunologists independently reviewed the questionnaires, as well as electronic health records, to determine whether the cases represented anaphylaxis and whether ED epinephrine administration was appropriate. RESULTS: Among 174 patients enrolled in the study, 61 (35%) were confirmed to have anaphylaxis. Overall, 47 anaphylaxis patients (77%) received epinephrine either before ED arrival or in the ED. In the latter situation, 24 anaphylaxis patients (39%) received epinephrine and 37 (61%) did not. Of the patients who received ED epinephrine, the allergists-immunologists determined that its administration was appropriate in all cases (95% confidence interval [CI], 83%-100%). Among the 37 patients who did not receive ED epinephrine, the allergists-immunologists determined that nonadministration of epinephrine was appropriate in 36 patients (97%; 95% CI, 84%-100%). The allergists-immunologists determined that overall, ED management was appropriate for 60 (98%) of 61 patients with anaphylaxis (95% CI, 90%-100%). CONCLUSIONS: Although more than 60% of anaphylaxis patients did not receive epinephrine in the ED, the allergists-immunologists deemed ED management appropriate in 98% of total cases. Previous retrospective studies may underestimate the appropriateness of ED anaphylaxis management, particularly when prehospital epinephrine administration is not reported. PMID- 26542796 TI - Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). AB - Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1alpha), specific ECM molecules up regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically. PMID- 26542797 TI - The role of Interleukin Receptor Associated Kinase (IRAK)-M in regulation of myofibroblast phenotype in vitro, and in an experimental model of non-reperfused myocardial infarction. AB - In the infarcted myocardium, necrotic cardiomyocytes activate innate immune pathways, stimulating pro-inflammatory signaling cascades. Although inflammation plays an important role in clearance of the infarct from dead cells and matrix debris, repair of the infarcted heart requires timely activation of signals that negatively regulate the innate immune response, limiting inflammatory injury. We have previously demonstrated that Interleukin receptor-associated kinase (IRAK) M, a member of the IRAK family that suppresses toll-like receptor/interleukin-1 signaling, is upregulated in the infarcted heart in both macrophages and fibroblasts, and restrains pro-inflammatory activation attenuating adverse remodeling. Although IRAK-M is known to suppress inflammatory activation of macrophages, its role in fibroblasts remains unknown. Our current investigation examines the effects of IRAK-M on fibroblast phenotype and function. In vitro, IRAK-M null cardiac fibroblasts have impaired capacity to contract free-floating collagen pads. IRAK-M loss reduces transforming growth factor (TGF)-beta-mediated alpha-smooth muscle actin (alpha-SMA) expression. IRAK-M deficient cardiac fibroblasts exhibit a modest reduction in TGF-beta-stimulated Smad activation and increased expression of the alpha-SMA repressor, Y-box binding protein (YB)-1. In a model of non-reperfused myocardial infarction, IRAK-M absence does not affect collagen content and myofibroblast density in the infarcted and remodeling myocardium, but increases YB-1 levels and is associated with attenuated alpha-SMA expression in isolated infarct myofibroblasts. Our findings suggest that, in addition to its role in restraining inflammation following reperfused infarction, IRAK-M may also contribute to myofibroblast conversion. PMID- 26542798 TI - Palliative enteral feeding for patients with malignant esophageal obstruction: a retrospective study. AB - BACKGROUND: Malignant esophageal obstruction leads to dysphagia, deterioration in quality of life, and malnutrition. Traditional bedside nasogastric (NG) tube placement is very difficult under these circumstances. However, endoscopically assisted NG tube placement under fluoroscopic guidance could be an alternative option for establishing palliative enteral nutrition. This study aimed to compare the clinical outcomes of enteral tube feeding and esophageal stenting for patients with malignant esophageal obstruction and a short life expectancy. METHODS: Thirty-one patients were divided into 3 groups according to their treatment modality: NG tube (n = 12), esophageal stent group (n = 10), and supportive care with nil per os (NPO) (n = 9). Enteral nutrition, clinical outcomes, length of hospital stay, and median survival were evaluated. RESULTS: There were no significant baseline differences among the groups, except in age. The tube and stent groups had significantly higher enteral calorie intake (p = 0.01), higher serum albumin (p < 0.01), shorter hospital stay (p = 0.01), and longer median survival (p < 0.01) than the NPO group. The incidence of dislodgement in the tube group was significantly higher than in the stent group (58% vs. 20%, respectively; p = 0.01). However, stenting costs more than NG tube placement. CONCLUSIONS: Palliative enteral feeding by NG tube is safe, inexpensive, and has a low complication rate. Endoscopically assisted NG tube placement under fluoroscopic guidance could be a feasible palliative option for malignant esophageal obstruction for patients who have a short life expectancy. PMID- 26542799 TI - Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis. AB - The potassium channel Kv1.3 plays roles in immunity, neuronal development and sensory discrimination. Regulation of Kv1.3 by kinase signaling has been studied. In this context, EGF binds to specific receptors (EGFR) and triggers tyrosine kinase-dependent signaling, which down-regulates Kv1.3 currents. We show that Kv1.3 undergoes EGF-dependent endocytosis. This EGF-mediated mechanism is relevant because is involved in adult neural stem cell fate determination. We demonstrated that changes in Kv1.3 subcellular distribution upon EGFR activation were due to Kv1.3 clathrin-dependent endocytosis, which targets the Kv1.3 channels to the lysosomal degradative pathway. Interestingly, our results further revealed that relevant tyrosines and other interacting motifs, such as PDZ and SH3 domains, were not involved in the EGF-dependent Kv1.3 internalization. However, a new, and yet undescribed mechanism, of ERK1/2-mediated threonine phosphorylation is crucial for the EGF-mediated Kv1.3 endocytosis. Our results demonstrate that EGF triggers the down-regulation of Kv1.3 activity and its expression at the cell surface, which is important for the development and migration of adult neural progenitors. PMID- 26542800 TI - Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota. AB - Despite significant progress in understanding the homeostatic regulation of energy balance, successful therapeutic options for curbing obesity remain elusive. One potential target for the treatment of obesity is via manipulation of the gut-brain axis, a complex bidirectional communication system that is crucial in maintaining energy homeostasis. Indeed, ingested nutrients induce secretion of gut peptides that act either via paracrine signaling through vagal and non-vagal neuronal relays, or in an endocrine fashion via entry into circulation, to ultimately signal to the central nervous system where appropriate responses are generated. We review here the current hypotheses of nutrient sensing mechanisms of enteroendocrine cells, including the release of gut peptides, mainly cholecystokinin, glucagon-like peptide-1, and peptide YY, and subsequent gut-to brain signaling pathways promoting a reduction of food intake and an increase in energy expenditure. Furthermore, this review highlights recent research suggesting this energy regulating gut-brain axis can be influenced by gut microbiota, potentially contributing to the development of obesity. PMID- 26542801 TI - Epigenesis and plasticity of mouse trophoblast stem cells. AB - The critical role of the placenta in supporting a healthy pregnancy is mostly ensured by the extraembryonic trophoblast lineage that acts as the interface between the maternal and the foetal compartments. The diverse trophoblast cell subtypes that form the placenta originate from a single layer of stem cells that emerge from the embryo when the earliest cell fate decisions are occurring. Recent studies show that these trophoblast stem cells exhibit extensive plasticity as they are capable of differentiating down multiple pathways and are easily converted into embryonic stem cells in vitro. In this review, we discuss current knowledge of the mechanisms and control of the epigenesis of mouse trophoblast stem cells through a comparison with the corresponding mechanisms in pluripotent embryonic stem cells. To illustrate some of the more striking manifestations of the epigenetic plasticity of mouse trophoblast stem cells, we discuss them within the context of two paradigms of epigenetic regulation of gene expression: the imprinted gene expression of specific loci and the process of X chromosome inactivation. PMID- 26542803 TI - MicroRNA-7 Compromises p53 Protein-dependent Apoptosis by Controlling the Expression of the Chromatin Remodeling Factor SMARCD1. AB - We previously demonstrated that the epidermal growth factor receptor (EGFR) up regulated miR-7 to promote tumor growth during lung cancer oncogenesis. Several lines of evidence have suggested that alterations in chromatin remodeling components contribute to cancer initiation and progression. In this study, we identified SMARCD1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 1) as a novel target gene of miR-7. miR-7 expression reduced SMARCD1 protein expression in lung cancer cell lines. We used luciferase reporters carrying wild type or mutated 3'UTR of SMARCD1 and found that miR-7 blocked SMARCD1 expression by binding to two seed regions in the 3'UTR of SMARCD1 and down-regulated SMARCD1 mRNA expression. Additionally, upon chemotherapy drug treatment, miR-7 down-regulated p53-dependent apoptosis-related gene BAX (BCL2-associated X protein) and p21 expression by interfering with the interaction between SMARCD1 and p53, thereby reducing caspase3 cleavage and the downstream apoptosis cascades. We found that although SMARCD1 sensitized lung cancer cells to chemotherapy drug-induced apoptosis, miR-7 enhanced the drug resistance potential of lung cancer cells against chemotherapy drugs. SMARCD1 was down-regulated in patients with non-small cell lung cancer and lung adenocarcinoma cell lines, and SMARCD1 and miR-7 expression levels were negatively correlated in clinical samples. Our investigation into the involvement of the EGFR-regulated microRNA pathway in the SWI/SNF chromatin remodeling complex suggests that EGFR-mediated miR-7 suppresses the coupling of the chromatin remodeling factor SMARCD1 with p53, resulting in increased chemo resistance of lung cancer cells. PMID- 26542804 TI - The Voltage-dependent Anion Channel 1 Mediates Amyloid beta Toxicity and Represents a Potential Target for Alzheimer Disease Therapy. AB - The voltage-dependent anion channel 1 (VDAC1), found in the mitochondrial outer membrane, forms the main interface between mitochondrial and cellular metabolisms, mediates the passage of a variety of molecules across the mitochondrial outer membrane, and is central to mitochondria-mediated apoptosis. VDAC1 is overexpressed in post-mortem brains of Alzheimer disease (AD) patients. The development and progress of AD are associated with mitochondrial dysfunction resulting from the cytotoxic effects of accumulated amyloid beta (Abeta). In this study we demonstrate the involvement of VDAC1 and a VDAC1 N-terminal peptide (VDAC1-N-Ter) in Abeta cell penetration and cell death induction. Abeta directly interacted with VDAC1 and VDAC1-N-Ter, as monitored by VDAC1 channel conductance, surface plasmon resonance, and microscale thermophoresis. Preincubated Abeta interacted with bilayer-reconstituted VDAC1 and increased its conductance ~ 2 fold. Incubation of cells with Abeta resulted in mitochondria-mediated apoptotic cell death. However, the presence of non-cell-penetrating VDAC1-N-Ter peptide prevented Abeta cellular entry and Abeta-induced mitochondria-mediated apoptosis. Likewise, silencing VDAC1 expression by specific siRNA prevented Abeta entry into the cytosol as well as Abeta-induced toxicity. Finally, the mode of Abeta mediated action involves detachment of mitochondria-bound hexokinase, induction of VDAC1 oligomerization, and cytochrome c release, a sequence of events leading to apoptosis. As such, we suggest that Abeta-mediated toxicity involves mitochondrial and plasma membrane VDAC1, leading to mitochondrial dysfunction and apoptosis induction. The VDAC1-N-Ter peptide targeting Abeta cytotoxicity is thus a potential new therapeutic strategy for AD treatment. PMID- 26542805 TI - Analysis of Perforin Assembly by Quartz Crystal Microbalance Reveals a Role for Cholesterol and Calcium-independent Membrane Binding. AB - Perforin is an essential component in the cytotoxic lymphocyte-mediated cell death pathway. The traditional view holds that perforin monomers assemble into pores in the target cell membrane via a calcium-dependent process and facilitate translocation of cytotoxic proteases into the cytoplasm to induce apoptosis. Although many studies have examined the structure and role of perforin, the mechanics of pore assembly and granzyme delivery remain unclear. Here we have employed quartz crystal microbalance with dissipation monitoring (QCM-D) to investigate binding and assembly of perforin on lipid membranes, and show that perforin monomers bind to the membrane in a cooperative manner. We also found that cholesterol influences perforin binding and activity on intact cells and model membranes. Finally, contrary to current thinking, perforin efficiently binds membranes in the absence of calcium. When calcium is added to perforin already on the membrane, the QCM-D response changes significantly, indicating that perforin becomes membranolytic only after calcium binding. PMID- 26542806 TI - E3 Ubiquitin Ligase Fbw7 Negatively Regulates Osteoblast Differentiation by Targeting Runx2 for Degradation. AB - Runx2, a master regulator of osteoblast differentiation, is tightly regulated at both transcriptional and post-translational levels. Post-translational modifications such as phosphorylation and ubiquitination have differential effects on Runx2 functions. Here, we show that the reduced expression and functions of Runx2 upon its phosphorylation by GSK3beta are mediated by its ubiquitin-mediated degradation through E3 ubiquitin ligase Fbw7alpha. Fbw7alpha through its WD domain interacts with Runx2 both in a heterologous (HEK293T cells) system as well as in osteoblasts. GSK3beta was also present in the same complex as determined by co-immunoprecipitation. Furthermore, overexpression of either Fbw7alpha or GSK3beta was sufficient to down-regulate endogenous Runx2 expression and function; however, both failed to inhibit endogenous Runx2 when either of them was depleted in osteoblasts. Fbw7alpha-mediated inhibition of Runx2 expression also led to reduced Runx2 transactivation and osteoblast differentiation. In contrast, inhibition of Fbw7alpha restored Runx2 levels and promoted osteoblast differentiation. We also observed reciprocal expression levels of Runx2 and Fbw7alpha in models of bone loss such as lactating (physiological bone loss condition) and ovariectomized (induction of surgical menopause) animals that show reduced Runx2 and enhanced Fbw7alpha, whereas this was reversed in the estrogen-treated ovariectomized animals. In addition, methylprednisolone (a synthetic glucocorticoid) treatment to neonatal rats showed a temporal decrease in Runx2 with a reciprocal increase in Fbw7 in their calvarium. Taken together, these data demonstrate that Fbw7alpha negatively regulates osteogenesis by targeting Runx2 for ubiquitin-mediated degradation in a GSK3beta-dependent manner and thus provides a plausible explanation for GSK3beta mediated bone loss as described before. PMID- 26542802 TI - Neuronal correlates of depression. AB - Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present, the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations show that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesises findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the aetiology of depression. PMID- 26542807 TI - In Silico Prediction of Human Sulfotransferase 1E1 Activity Guided by Pharmacophores from Molecular Dynamics Simulations. AB - Acting during phase II metabolism, sulfotransferases (SULTs) serve detoxification by transforming a broad spectrum of compounds from pharmaceutical, nutritional, or environmental sources into more easily excretable metabolites. However, SULT activity has also been shown to promote formation of reactive metabolites that may have genotoxic effects. SULT subtype 1E1 (SULT1E1) was identified as a key player in estrogen homeostasis, which is involved in many physiological processes and the pathogenesis of breast and endometrial cancer. The development of an in silico prediction model for SULT1E1 ligands would therefore support the development of metabolically inert drugs and help to assess health risks related to hormonal imbalances. Here, we report on a novel approach to develop a model that enables prediction of substrates and inhibitors of SULT1E1. Molecular dynamics simulations were performed to investigate enzyme flexibility and sample protein conformations. Pharmacophores were developed that served as a cornerstone of the model, and machine learning techniques were applied for prediction refinement. The prediction model was used to screen the DrugBank (a database of experimental and approved drugs): 28% of the predicted hits were reported in literature as ligands of SULT1E1. From the remaining hits, a selection of nine molecules was subjected to biochemical assay validation and experimental results were in accordance with the in silico prediction of SULT1E1 inhibitors and substrates, thus affirming our prediction hypotheses. PMID- 26542808 TI - Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex. AB - The heterotetrameric (epsilon-beta4-MU4-sigma4) complex adaptor protein 4 (AP-4) is a component of a non-clathrin coat involved in protein sorting at the trans Golgi network (TGN). Considerable interest in this complex has arisen from the recent discovery that mutations in each of its four subunits are the cause of a congenital intellectual disability and movement disorder in humans. Despite its physiological importance, the structure and function of this coat remain poorly understood. To investigate the assembly of the AP-4 coat, we dissected the determinants of interaction of AP-4 with its only known accessory protein, the ENTH/VHS-domain-containing protein tepsin. Using a variety of protein interaction assays, we found that tepsin comprises two phylogenetically conserved peptide motifs, [GS]LFXG[ML]X[LV] and S[AV]F[SA]FLN, within its C-terminal unstructured region, which interact with the C-terminal ear (or appendage) domains of the beta4 and epsilon subunits of AP-4, respectively. Structure-based mutational analyses mapped the binding site for the [GS]LFXG[ML]X[LV] motif to a conserved, hydrophobic surface on the beta4-ear platform fold. Both peptide-ear interactions are required for efficient association of tepsin with AP-4, and for recruitment of tepsin to the TGN. The bivalency of the interactions increases the avidity of tepsin for AP-4 and may enable cross-linking of multiple AP-4 heterotetramers, thus contributing to the assembly of the AP-4 coat. In addition to revealing critical aspects of this coat, our findings extend the paradigm of peptide-ear interactions, previously established for clathrin-AP-1/AP-2 coats, to a non clathrin coat. PMID- 26542810 TI - Effect of dietary lactulose supplementation on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. AB - A 35 d trial was conducted to evaluate the effects of dietary lactulose on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. A total of 816 1-day-old male Ross broilers (40.2 +/- 0.4 g) were allotted to 4 dietary treatments using 12 cages with 17 chicks per cage. Treatments were: 1) CON, basal diet; 2) L05, CON + 0.05% lactulose; 3) L10, CON + 0.10% lactulose; and 4) L15, CON + 0.15% lactulose. Higher (P < 0.05) body weight gain (BWG) and lower (P < 0.05) feed conversion ratio (FCR) were observed in broilers fed the L15 diet compared with those fed the CON diet during d 22 to 35. During d 0 to 35, BWG was higher (P < 0.05) and FCR was lower (P < 0.05) in broilers fed lactulose diets than those fed the CON diet. Additionally, broilers fed L15 diets had the highest BWG (P < 0.05) and lowest FCR (P < 0.05). The apparent total tract digestibility (ATTD) of DM and nitrogen (N) was increased (P < 0.05) in broilers fed the L15 diet compared with those fed the CON diet. Drip loss was decreased (P < 0.05) in L10 and L15 treatments compared with CON treatment on d 1, d 3, and d 5. On d 3, lowest (P < 0.05) drip loss was observed in the L15 treatment. Excreta E. coli counts in the L15 treatment were decreased (P < 0.05) on d 14, but Lactobacillus counts in the L15 treatment were increased (P < 0.05) on d 14 and d 35 compared with the CON diet. A linear effect (P < 0.05) was observed on BWG (d 22 to 35), FCR (d 0 to 35), the ATTD of DM and N, drip loss, E. coli (d 14), and Lactobacillus (d 14 and d 35) counts. In conclusion, dietary supplementation of 0.15% lactulose can improve growth performance and nutrient digestibility; as well as increase the proliferation of Lactobacillus and decrease E. coli counts in excreta. PMID- 26542809 TI - Effects of adrenomedullin on the expression of inflammatory cytokines and chemokines in oviducts from women with tubal ectopic pregnancy: an in-vitro experimental study. AB - BACKGROUND: The occurrence of tubal ectopic pregnancy (tEP) is related to the inflammation of the oviduct. Recently, Adrenomedullin (ADM) was found highly expression in human oviduct. The current study is to investigate whether ADM have a modulatory action on inflammatory cytokines and chemokines in oviductal tissue from women with tubal ectopic pregnancy (tEP). METHODS: Oviductal isthmus samples were collected from women with tEP undergoing salpingectomy, and women undergoing hysterectomy for benign gynaecological conditions. The mRNA and protein levels of inflammatory cytokines/chemokines were assayed by PCR (n = 6 for tEP, n = 5 for controls) and protein microarray methods (n = 5 for both tEP and controls) respectively. RESULTS: Some of the inflammatory cytokines/chemokines were upregulated by ADM in oviducts from tEP patients at both mRNA and protein levels. Incubation of oviduct from tEP patients with ADM for 24 h down-regulated some of these cytokines/chemokines. CONCLUSION: Our results suggest an additional mechanism whereby ADM insufficiency may increase the susceptibility to tEP through diminished anti-inflammatory activity. The actual impact of the relationship between ADM and inflammatory process on tubal implantation needs further exploration. PMID- 26542811 TI - Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive like behaviors in rats. AB - Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic pituitary-adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30 min of treadmill running at different speeds (high speed, 25 m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects. PMID- 26542812 TI - Changes in spatial cognition and brain activity after a single dose of testosterone in healthy women. AB - Studies have consistently shown that males perform better than females on several spatial tasks. Animal and human literature suggests that sex hormones have an important role in both establishing and maintaining this difference. The aim of the present study was to examine the effects of exogenous testosterone on spatial cognition and brain activity in healthy women. A cross-sectional, double-blind, randomized, placebo-controlled study was performed in 42 healthy young women who either received one dose of 0.5mg sublingual testosterone or placebo. They then learned a virtual environment and performed navigation tasks during functional magnetic resonance imaging (fMRI). Subsequently, their knowledge of the virtual environment, self-reported navigation strategy, and mental rotation abilities were measured. The testosterone group had improved representations of the directions within the environment and performed significantly better on the mental rotation task compared to the placebo group, but navigation success and navigation strategy were similar in the two groups. Nevertheless, the testosterone group had significantly increased activity within the medial temporal lobe during successful navigation compared to the placebo group, and a positive correlation between testosterone load and medial temporal lobe activity was found. Fetal testosterone levels, measured as second-to-fourth digit length ratio, interacted significantly with parahippocampal activity and tended towards giving higher mental rotation task scores. These results demonstrated that testosterone had a limited effect pertaining specifically to spatial cognition involving 3D-visualization in healthy women, while complex behaviors such as navigation, relying more on learned strategies, were not altered despite increased neuronal activity in relevant brain regions. PMID- 26542813 TI - Greater neurobehavioral deficits occur in adult mice after repeated, as compared to single, mild traumatic brain injury (mTBI). AB - Mild traumatic brain injury (mTBI) accounts for the majority of all brain injuries and affected individuals typically experience some extent of cognitive and/or neuropsychiatric deficits. Given that repeated mTBIs often result in worsened prognosis, the cumulative effect of repeated mTBIs is an area of clinical concern and on-going pre-clinical research. Animal models are critical in elucidating the underlying mechanisms of single and repeated mTBI-associated deficits, but the neurobehavioral sequelae produced by these models have not been well characterized. Thus, we sought to evaluate the behavioral changes incurred after single and repeated mTBIs in mice utilizing a modified impact-acceleration model. Mice in the mTBI group received 1 impact while the repeated mTBI group received 3 impacts with an inter-injury interval of 24h. Classic behavior evaluations included the Morris water maze (MWM) to assess learning and memory, elevated plus maze (EPM) for anxiety, and forced swim test (FST) for depression/helplessness. Additionally, species-typical behaviors were evaluated with the marble-burying and nestlet shredding tests to determine motivation and apathy. Non-invasive vibration platforms were used to examine sleep patterns post mTBI. We found that the repeated mTBI mice demonstrated deficits in MWM testing and poorer performance on species-typical behaviors. While neither single nor repeated mTBI affected behavior in the EPM or FST, sleep disturbances were observed after both single and repeated mTBI. Here, we conclude that behavioral alterations shown after repeated mTBI resemble several of the deficits or disturbances reported by patients, thus demonstrating the relevance of this murine model to study repeated mTBIs. PMID- 26542814 TI - Concurrent antagonism of NMDA and AMPA receptors in the ventral tegmental area reduces the expression of conditioned approach learning in rats. AB - Conditioned stimuli (CSs) come to function as CSs by acquiring the capacity to activate the same mesocorticolimbic dopamine (DA) neurons activated by primary rewards, producing conditioned activation of these neurons and their associated motivational states. This model stipulates that CSs activate mesocorticolimbic DA systems through the activation of glutamate receptors on DA neurons in the ventral tegmental area (VTA). We tested the hypothesis that glutamate receptor stimulation in the VTA is necessary for the expression of conditioned approach. Rats were tested in a conditioned approach protocol that consisted of 7 consecutive conditioning sessions (light presentations and food were paired), one session with no light or food and one test session with only light stimulus (CS only) presentations. The number of head entries during the CS and pre-CS (baseline) periods was used to calculate difference scores. Bilateral VTA microinjections of glutamate receptor antagonists were made prior to the CS-only session. Kynurenic acid (ionotropic glutamate receptor antagonist; 1.125-4.5 MUg/0.5 MUl) significantly reduced difference scores compared to vehicle (0 MUg), whereas MCPG (metabotropic glutamate receptor antagonist; 1.875-7.5 MUg), AP-5 (NMDA antagonist; 0.03125-2.0 MUg), and NBQX (AMPA antagonist; 0.5-4.0 MUg) had no effects. When AP-5 and NBQX were administered simultaneously at doses of 0.25/4.0 and 2.0/4.0 MUg, respectively, the combination significantly reduced the difference scores compared to 0/0 MUg, indicating a reduction in the expression of conditioned approach. These findings indicate that expression of conditioned approach learning requires NMDA or AMPA receptor stimulation in the VTA. PMID- 26542815 TI - A retrospective, multicenter analysis of the predictive value of mitotic rate for sentinel lymph node (SLN) positivity in thin melanomas. AB - BACKGROUND: There is a paucity of studies to substantiate whether the presence of a single mitosis justifies sentinel lymph node (SLN) biopsy (SLNB) in thin melanomas. OBJECTIVE: We sought to determine if mitotic rate is associated with SLNB outcome when taking into account other prognostic factors. METHODS: All cases of melanoma that underwent SLNB in the province of Alberta, Canada, between 2007 and 2013 were reviewed through a provincial tumor database. RESULTS: A total of 1072 patients fulfilled inclusion criteria. When analyzing all melanomas regardless of thickness, mitotic rate was a good predictor of SLN status. When stratified by Breslow thickness, only intermediate melanomas (1.01-2.0 mm) demonstrated a significant relationship between mitotic rate and positive SLN status (P = .010). For melanomas 1 mm or smaller, mitotic rate was not associated with SLN status. A statistically significant interaction was identified between Breslow thickness and mitotic rate such that for decreasing Breslow depth, the effect of mitotic rate on SLNB status diminished (P = .028). LIMITATIONS: The study was retrospective in nature. There is underlying variability in mitotic rate reporting methods over time, and between different dermatopathologists. CONCLUSIONS: Mitotic rate does not have unequivocal utility in predicting SLNB status in thin melanomas. There is a significant interaction between mitotic rate and Breslow depth, such that the predictive value of mitotic rate on SLN positivity may be dependent on Breslow thickness. PMID- 26542816 TI - Using the Autism-Spectrum Quotient to Measure Autistic Traits in Anorexia Nervosa: A Systematic Review and Meta-Analysis. AB - Interest in the link between Autism Spectrum Disorder (ASD) and Anorexia Nervosa (AN) has led to estimates of the prevalence of autistic traits in AN. This systematic review and meta-analysis assessed the use of the Autism-Spectrum Quotient (AQ) or abbreviated version (AQ-10) to examine whether patients with AN have elevated levels of autistic traits. Seven studies were identified and subsequent meta-analysis indicated that those with AN appear to have significant difficulties of a manner characteristic of ASD, relative to controls. Whilst this analysis supports previous indications of higher prevalence of ASD in AN, the aetiology of these traits remains unclear. Studies using more robust clinical measures of ASD within AN are needed to confirm what self-report measures appear to show. PMID- 26542818 TI - Giant accessory breast: a rare occurrence reported, with a review of the literature. AB - Polymastia, or the presence of supranumerary breasts, occurs in 2-6% of the female population, the spectrum of the disorder ranging between a small mole and a fully functional ectopic breast. They are often asymptomatic but require treatment when symptomatic or if they harbour malignancy. We present a case of a 41-year-old woman with an accessory breast in the left inframammary fold, which increased in size over the decade following her first pregnancy, to reach a size almost three times that of her right breast. Preoperative fine-needle aspiration and ultrasound was suggestive of accessory breast tissue, distinct from the left breast. Intraoperatively, a 14*10*8 cm accessory breast was found in the inframammary fold, distinct from the left breast and having an accessory nipple areola complex as well. A simple mastectomy was performed with trimming and rotation of the inframammary flap. The patient was happy with the cosmetic outcome. This article also reviews the literature and covers classification of polymastia, diagnostic complexities and challenges associated with surgery. PMID- 26542819 TI - NtRING1, putative RING-finger E3 ligase protein, is a positive regulator of the early stages of elicitin-induced HR in tobacco. AB - KEY MESSAGE: NtRING1 is a RING-finger protein with a putative E3 ligase activity. NtRING1 regulates HR establishment against different pathogens. Loss-/gain-of function of NtRING1 altered early stages of HR phenotype establishment. Plant defence responses against pathogens often involve the restriction of pathogens by inducing a hypersensitive response (HR). cDNA clones DD11-39, DD38-11 and DD34-26 were previously obtained from a differential screen aimed at characterising tobacco genes with an elicitin-induced HR-specific pattern of expression. Our precedent observations suggested that DD11-39, DD38-11 and DD34-26 might play roles in the HR establishment. Only for DD11-39 a full-length cDNA sequence was obtained and the corresponding protein encoded for a type-HC RING-finger/putative E3 ligase protein which we termed NtRING1. The expression of NtRING1 was upregulated upon HR induction by elicitin, Ralstonia solanacearum, or tobacco mosaic virus (TMV) in tobacco. Silencing of NtRING1 remarkably delayed the establishment of elicitin-induced HR in tobacco as well as the expression of different early induction genes in tissues undergoing HR. Accordingly, transient overexpression of NtRING1 accelerated the HR launching upon elicitin treatment. Taking together, our data suggests that NtRING1 plays a functional role in the early establishment of HR. PMID- 26542820 TI - Evaluating the Siebens Model in Geriatric-Stroke Inpatient Rehabilitation to Reduce Institutionalization and Acute-Care Readmissions. AB - BACKGROUND: The objective of the study is to evaluate the use of Siebens Domain Management Model (SDMM) in geriatric-stroke patients during inpatient rehabilitation (IR) to increase functional independence, and to reduce institutionalization and acute-care readmissions, which are quality indicators under the U.S. Affordable Care Act. METHODS: In 2010 (preintervention), 66 stroke patients aged more than 75 years were admitted to an IR facility, on average, 8.8 days postacute care. In 2012 (postintervention), 58 patients aged more than 75 years were admitted to the same IR facility, on average, 5.0 days postacute care. SDMM intervention involved weekly adjustments of clinical care focused on potential barriers to discharge home. Functional Independence Measure (FIM) efficiency, length of stay (LOS), and disposition rates to community or home, acute care, and long-term care were compared pre- and postintervention within facility, and facility data were compared to national case-mix-group-adjusted data from the Uniform Data System for Medical Rehabilitation for both years (2010/2012). RESULTS: Pre- and postintervention demographics and prestroke living support/setting were similar, but preintervention had on average 4 more days LOS in IR and 3.8 more days to IR onset. There were significantly more discharges to community in postintervention (79.3%) compared to preintervention (56.9%) (chi square = 6.02, P < .013). The preintervention group did not significantly differ from 2010 national data whereas the postintervention/2012 group significantly differed from 2012 national data for higher FIM efficiency (t = -3.1, P < .002) and more discharges to community (chi-square = 19.7; P < .0001). From 2010 to 2012, there were 3.8 times more discharges to community (chi-square = 8535; P < .0001) and 6 times fewer acute-care dispositions postintervention than nationally (chi-square = 58.7; P < .0001). PMID- 26542821 TI - Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants--Case Series and Systematic Review of Reported Cases. AB - BACKGROUND: Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature. METHODS: We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding. RESULTS: Between October 2010 and October 2014, 6 patients received IV tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method: .8 21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 +/- 7.8 [4-28.3] hours. CONCLUSIONS: Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy. PMID- 26542822 TI - Distance to Thrombus in Acute Middle Cerebral Artery Occlusion Predicts Target Mismatch and Ischemic Penumbra. AB - BACKGROUND AND PURPOSE: In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics. METHODS: Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated. RESULTS: Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR] = .89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69. CONCLUSIONS: DT correlates inversely with Tmax perfusion deficits and mismatch volumes and acts as an independent predictor of target mismatch. PMID- 26542823 TI - Development and Assessment of a Computer Algorithm for Stroke Vascular Localization Using Components of the National Institutes of Health Stroke Scale. AB - BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) was not intended to be used to determine the stroke's vascular distribution. The aim of this study was to develop, assess the reliability, and validate a computer algorithm based on the NIHSS for this purpose. METHODS: Two cohorts of patients with ischemic stroke having similar distributions of Oxfordshire localizations (total anterior, partial anterior, lacunar, and posterior circulation) based on neuroimaging were identified. The first cohort (n = 40) was used to develop a computer algorithm for vascular localization using a modified version of the NIHSS (NIHSS-Localization [NIHSS-Loc]) that included the laterality of selected deficits; the second (n = 20) was used to assess the reliability of algorithm based localizations compared to those of 2 vascular neurologists. The validity of the algorithm-based localizations was assessed in comparison to neuroimaging. Agreement was assessed using the unweighted kappa (kappa) statistic. RESULTS: Agreement between the 2 raters using the standard NIHSS was slight to moderate (kappa = .36, 95% confidence interval [CI] .10-.61). Inter-rater agreement significantly improved to the substantial to almost perfect range using the NIHSS Loc (kappa = .88, 95% CI .73-1.00). Agreement was perfect when the 2 raters entered the data into the NIHSS-Loc computer algorithm (kappa = 1.00, 95% CI 1.00 1.00). Agreement between the algorithm localization and neuroimaging results was fair to moderate (kappa = .59, 95% CI .35-.84) and not significantly different from the localizations of either rater using the NIHSS-Loc. CONCLUSION: A computerized, modified version of the standard NIHSS can be used to reliably and validly assign the vascular distribution of an acute ischemic stroke. PMID- 26542824 TI - Predicting Paroxysmal Atrial Fibrillation in Cerebrovascular Ischemia Using Tissue Doppler Imaging and Speckle Tracking Echocardiography. AB - BACKGROUND: Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit. AIM: The objective of the study is to investigate whether advanced echocardiography improves the diagnostic approach for PAF in CI. METHODS: The study included 286 CI patients with an echocardiogram in sinus rhythm. Patients were divided by PAF occurrence (PAF: n = 86, non-PAF: n = 200). PAF was defined as 1 or more reported episodes of atrial fibrillation. Echocardiograms consisted of conventional measures, tissue Doppler imaging (TDI), and speckle tracking. TDI was performed to acquire myocardial peak velocities during systole/ventricular contraction (global s'), early diastole/ventricular filling (global e'), and late diastole/atrial contraction (global a'). Speckle tracking was performed for myocardial strain analysis, thereby retrieving global longitudinal strain and global strain rate (s, e, a) values. RESULTS: Patients with PAF exhibited significantly impaired atrial contractile measures: global a' (-7.0 cm/second versus -5.7 cm/second, P < .001) and global strain rate a (.97 second(-1) versus .81 second(-1), P < .001). Both were univariable markers of PAF, and along with age remained the only independent significant determinants of PAF after multivariable logistic regression. Area under the curve (AUC) for age, global a', and global strain rate a significantly exceeded AUC for age alone (.79 versus .76, P = .032). Cutoff values with the highest sensitivity and specificity for these 3 parameters improved the diagnostic accuracy (sensitivity = 97%, specificity = 32%, negative predictive value = 95%, and positive predictive value = 38%). CONCLUSIONS: Atrial contractile measures by advanced echocardiography are significant determinants of PAF in CI. However, there is no discriminatory power to make them clinically useful at the current moment. PMID- 26542825 TI - Herpes Simplex Virus Type 2 Encephalitis as a Cause of Ischemic Stroke: Case Report and Systematic Review of the Literature. AB - BACKGROUND AND AIM: Our objective is to describe a patient who developed an ischemic stroke as a complication of herpes simplex virus type 2 (HSV-2) encephalitis and to review the literature. PATIENTS AND METHODS: A 45-year-old immune-competent Caucasian man presented with a 24-hour history of confusion and fever, and following clinical and laboratory examination was diagnosed with HSV-2 encephalitis. However, the brain magnetic resonance imaging also showed an acute ischemic infarct in the left frontal lobe corresponding to vascular territories of middle cerebral artery branches. Further screening failed to identify any other cause of the stroke. A systematic literature search was conducted in February 2015 using the PubMed database. RESULTS: Six more cases of herpes simplex virus (HSV) central nervous system (CNS) infection that developed a definite ischemic stroke as a complication of the infection were identified. CONCLUSIONS: Ischemic stroke, although infrequent, can complicate the evolution of herpes simplex meningitis or encephalitis. Clinicians should include HSV CNS infection as a possible cause of ischemic stroke, especially in young patients with ischemic stroke of unknown etiology. PMID- 26542826 TI - Adding ultrasound to mammography could increase breast cancer detection in Asian women. PMID- 26542827 TI - Altering sensorimotor feedback disrupts visual discrimination of facial expressions. AB - Looking at another person's facial expression of emotion can trigger the same neural processes involved in producing the expression, and such responses play a functional role in emotion recognition. Disrupting individuals' facial action, for example, interferes with verbal emotion recognition tasks. We tested the hypothesis that facial responses also play a functional role in the perceptual processing of emotional expressions. We altered the facial action of participants with a gel facemask while they performed a task that involved distinguishing target expressions from highly similar distractors. Relative to control participants, participants in the facemask condition demonstrated inferior perceptual discrimination of facial expressions, but not of nonface stimuli. The findings suggest that somatosensory/motor processes involving the face contribute to the visual perceptual-and not just conceptual-processing of facial expressions. More broadly, our study contributes to growing evidence for the fundamentally interactive nature of the perceptual inputs from different sensory modalities. PMID- 26542828 TI - The influence of high temperature on the possibility of DNA typing in various human tissues. AB - INTRODUCTION: The identification of unknown victims of high temperatures (fire, terrorist attack, and other disasters) is one of the most difficult tasks faced by forensic geneticists. The main aim of this study was to in-vestigate the availability of DNA isolated from various human tissue samples exposed to high temperatures of 100-1000 degrees C for 5 and 10 minutes. MATERIAL AND METHODS: Samples of varying thickness of thigh muscle, liver, heart, adipose tissue, bone, teeth, hair and nails of 52 fresh cadavers and 59 healthy teeth of 29 volunteers were used. The study was performed using the following commercially available STR (Short Tandem Repeats) and miniSTR kits: AmpFlSTR(r)SGM Plus(r) and AmpFlSTR(r)MiniFilerTM. Hyper variable region I (HVI) of human mitochondrial DNA (mtDNA) was sequenced with BigDye Terminator Cycle Sequencing Kit 1.1. The PEP (Primer-Extension Preamplification) method was used for the whole human genome amplification. RESULTS: It was possible to obtain complete DNA profiles (AmpFlSTR(r)SGM Plus(r), AmpFlSTR(r)MiniFilerTM Applied Biosystems, USA and mtDNA HVI region) for tissue samples of heart, liver and thigh muscle, exposed up to 900 degrees C for 5 min. However, under the applied conditions, limited usefulness of hair, nails and teeth for identification purposes was shown. CONCLUSIONS: DNA stability in tissues subjected to incineration depends on many factors, like tissue type and its thickness, temperature and time of exposure. In the cases of human remains exposed to high temperatures, samples of soft tissues of the highest weight (thickness) provide the best chance of successful identification through the genetic analysis. In some cases of negative results, even if using mtDNA typing, application of the whole genome amplification (WGA) technique could provide the expected results for highly degraded DNA templates. PMID- 26542829 TI - Simultaneous detection of Cymbidium mosaic virus and Odontoglossum ringspot virus in orchids using multiplex RT-PCR. AB - A system for simultaneous detection of two orchid-infecting viruses was developed and applied to several orchid species. The detection system involved multiplex reverse transcription-polymerase chain reaction (RT-PCR) and could simultaneously identify Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) from the orchid species studied. Multiplex RT-PCR was conducted using two virus specific primer pairs and an internal control pair of primers to amplify the CymMV and ORSV coat protein regions, and orchid 18S rDNA, respectively. For optimization of multiplex RT-PCR conditions, serial dilutions of total RNA and cDNA were performed and the detection limit of the system was evaluated. The optimized multiplex detection system for CymMV and ORSV was applied to various orchid species, including several cultivars of Doritaenopsis, Cymbidium, Dendrobium, and Phalaenopsis to test the efficacy of this method. Our results indicate that the multiplex RT-PCR detection system will be a rapid, simple, and precise diagnosis tool in a range of orchid species. PMID- 26542830 TI - Recycling supercapacitors based on shredding and mild thermal treatment. AB - Supercapacitors are widely used in electric and hybrid vehicles, wind farm and low-power equipment due to their high specific power density and huge number of charge-discharge cycles. Waste supercapacitors should be recycled according to EU directive 2002/96/EC on waste electric and electronic equipment. This paper describes a recycling approach for end-of-life supercapacitors based on shredding and mild thermal treatment. At first, supercapacitors are shredded using a Retsch cutting mill. The shredded mixture is then undergone thermal treatment at 200 degrees C to recycle the organic solvent contained in the activated carbon electrodes. After the thermal treatment, the mixture is roughly separated using a fluidized bed method to remove the aluminium foil particles and paper particles from the activated carbon particles, which is subsequently put into water for a wet shredding into fine particles that can be re-used. The recycled activated carbon has a BET surface area of up to 1200m(2)/g and the recycled acetonitrile has a high purity. PMID- 26542831 TI - Brave new format. PMID- 26542832 TI - Reliability and utility of the Acute Care Index of Function in intensive care patients: An observational study. AB - OBJECTIVES: To establish the inter-rater reliability of the Acute Care Index of Function (ACIF) in intensive care unit (ICU) patients and determine whether ACIF scores have predictive utility beyond ICU discharge. BACKGROUND: Accurate and reliable measures of physical function are required to describe the recovery trajectory of ICU survivors. The clinimetric properties of the ACIF are yet to be established in ICU patients. METHODS: Prospective observational study in a single tertiary ICU. ACIF scores were recorded independently by 2 physiotherapists across a convenience sample of 100 physiotherapy assessments, and at ICU discharge. RESULTS: Inter-rater reliability of total ACIF scores was very strong (ICC = 0.94). ACIF <0.40 at ICU discharge predicted hospital discharge to a destination other than home (area under ROC = 0.79, 95% CI 0.64-0.89) (sensitivity 0.78). CONCLUSION: The ACIF has excellent inter-rater reliability in ICU patients and scores at ICU discharge predict the likelihood of discharge home. TRIAL REGISTRATION: ACTRN12614001008617 (September 18 2014). PMID- 26542833 TI - Determination of D-serine in human serum by LC-MS/MS using a triazole-bonded column after pre-column derivatization with (S)-4-(3-isothiocyanatopyrrolidin-1 yl)-7- (N, N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole. AB - An LC-MS/MS-based method for determining D-serine (Ser), an endogenous co-agonist of the N-methyl-D-aspartate receptor, in human serum, was developed and validated using a triazole-bonded silica-packed column after pre-column fluorescence derivatization with a chiral labeling reagent, (S)-4-(3-isothiocyanatopyrrolidin 1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole. Enantiomeric separation of the D- and L-Ser derivatives occurred in the triazole-bonded column (R s: 1.85) with CH3CN/100 mM HCO2NH4 in H2O (95.5:4.5) as the mobile phase with isocratic elution. The ln(capacity factor of D-Ser) in the van't Hoff plot gradually decreased with the inverse of temperature, suggesting enhanced hydrophilic interactions with the triazole-bonded stationary phase with increasing column temperature, owing to decrease in the partition coefficient to the mobile phase. Multiple reaction monitoring (m/z 457.10 > 409.00) by triple quadrupole mass spectrometry was used for quantifying D-Ser in human serum. The presence of D-Ser in the serum was confirmed by treatment with commercial D-amino acid oxidase. A linear calibration curve was constructed in the D-Ser concentration range of 0.5-5.0 MUM (r (2) = 0.999, n = 3) using D-homoserine as the internal standard. The precision and recovery values were adequate for quantification. The detection limit for D-Ser was 1.1 fmol/injection (signal-to noise ratio = 3), owing to the high CH3CN content in the mobile phase. The proposed LC-MS/MS method showed few fluctuations in the retention times of D- and L-Ser, and R s was stable until the 40th injection of serum without column washing, and thus can be useful for D-Ser determination in human serum in clinical research. PMID- 26542834 TI - Assessing similarity analysis of chromatographic fingerprints of Cyclopia subternata extracts as potential screening tool for in vitro glucose utilisation. AB - Similarity analysis of the phenolic fingerprints of a large number of aqueous extracts of Cyclopia subternata, obtained by high-performance liquid chromatography (HPLC), was evaluated as a potential tool to screen extracts for relative bioactivity. The assessment was based on the (dis)similarity of their fingerprints to that of a reference active extract of C. subternata, proven to enhance glucose uptake in vitro and in vivo. In vitro testing of extracts, selected as being most similar (n = 5; r >= 0.962) and most dissimilar (n = 5; r <= 0.688) to the reference active extract, showed that no clear pattern in terms of relative glucose uptake efficacy in C2C12 myocytes emerged, irrespective of the dose. Some of the most dissimilar extracts had higher glucose-lowering activity than the reference active extract. Principal component analysis revealed the major compounds responsible for the most variation within the chromatographic fingerprints, as mangiferin, isomangiferin, iriflophenone-3-C-beta-D-glucoside-4 O-beta-D-glucoside, iriflophenone-3-C-beta-D-glucoside, scolymoside, and phloretin-3',5'-di-C-beta-D-glucoside. Quantitative analysis of the selected extracts showed that the most dissimilar extracts contained the highest mangiferin and isomangiferin levels, whilst the most similar extracts had the highest scolymoside content. These compounds demonstrated similar glucose uptake efficacy in C2C12 myocytes. It can be concluded that (dis)similarity of chromatographic fingerprints of extracts of unknown activity to that of a proven bioactive extract does not necessarily translate to lower or higher bioactivity. PMID- 26542835 TI - Selective extraction and determination of fluoroquinolones in bovine milk samples with montmorillonite magnetic molecularly imprinted polymers and capillary electrophoresis. AB - A sensitive and selective method for separating fluoroquinolones (FQs) from bovine milk samples was successfully developed using montmorillonite magnetic molecularly imprinted polymers (MMMIPs) as adsorbents. MMMIPs were prepared using montmorillonite as carrier, fleroxacin (FLE) as template molecule, and Fe3O4 magnetite as magnetic component. MMMIPs possessed high adsorption capacity of 46.3 mg g(-1) for FLE. A rapid and convenient magnetic solid-phase extraction procedure coupled with capillary electrophoresis was established with MMMIPs as adsorbents for simultaneous and selective extraction of four FQs in bovine milk samples. Limits of detection ranged between 12.9 and 18.8 MUg L(-1), and the RSDs were between 1.8% and 8.6%. The proposed method was successfully applied to spike bovine milk samples with recoveries of 92.7%-108.6%. PMID- 26542836 TI - Effects of olanzapine on LPS-induced inflammation in rat primary glia cells. AB - Olanzapine (OLZ) is an atypical antipsychotic drug that also has mood-stabilizing effects. The mechanism of action of OLZ is not fully understood. Accumulating data suggest that inflammation plays a role in the pathophysiology of mental disorders and that psychotropic drugs exhibit some anti-inflammatory properties. This study was undertaken to examine the effects of OLZ on LPS-induced inflammation in rat primary glia cells. Glia cells were extracted from newborn rat brains. OLZ (1 or 50 uM) was added to culture medium at 6 or 72 h before addition of LPS for another 18 h, and levels of IL-10, prostaglandin (PG) E2, NO and TNF-alpha, and expression of cyclo-oxygensase (COX)-2 and inducible NO synthase (iNOS) were determined. Treatment with 50 uM OLZ (but not 1 uM) significantly decreased LPS-induced secretion of IL-10, PGE2 and TNF-alpha. In contrast, 50 uM OLZ significantly increased NO levels. OLZ did not alter the expression of COX-2 or iNOS in LPS-treated cells. These results suggest that OLZ differently affects the secretion of inflammatory mediators. Most of the significant effects of OLZ were obtained when 50 uM was used, which is a high and probably therapeutically irrelevant concentration. Therefore, under the conditions used in the present study OLZ seemed to lack a potent anti inflammatory effect. PMID- 26542837 TI - Diverse functions and reactions of class III peroxidases. AB - Higher plants contain plant-specific peroxidases (class III peroxidase; Prxs) that exist as large multigene families. Reverse genetic studies to characterize the function of each Prx have revealed that Prxs are involved in lignification, cell elongation, stress defense and seed germination. However, the underlying mechanisms associated with plant phenotypes following genetic engineering of Prx genes are not fully understood. This is because Prxs can function as catalytic enzymes that oxidize phenolic compounds while consuming hydrogen peroxide and/or as generators of reactive oxygen species. Moreover, biochemical efforts to characterize Prxs responsible for lignin polymerization have revealed specialized activities of Prxs. In conclusion, not only spatiotemporal regulation of gene expression and protein distribution, but also differentiated oxidation properties of each Prx define the function of this class of peroxidases. PMID- 26542838 TI - Novel methylene blue staining technique for localizing small esophageal leiomyomas during thoracoscopic enucleation. AB - The treatment of choice for leiomyoma, the most common benign esophageal tumor, is thoracoscopic enucleation. One of the most difficult aspects of thoracoscopic enucleation is the precise localization of small tumors (<=1.5 cm) and tumors without external protrusion. No simple, feasible solutions to this problem are available. We developed a novel methylene blue staining technique to localize small esophageal leiomyomas and evaluated the feasibility of our technique. Between January 2013 and July 2014, eight patients with small esophageal leiomyomas (<=1.5 cm) underwent thoracoscopic enucleation in Tongji Hospital. Preoperative endoscopic ultrasonography was performed in all patients. The leiomyomas were located in the middle (n = 5) and lower (n = 3) thirds of the esophagus. We preoperatively injected 0.5-1.0 mL methylene blue in the submucosa adjacent to the tumors under standard gastroscope guidance. The entire staining process took about 10 minutes. Staining was successful in all patients. The unstained tumor was exposed after the blue-stained mediastinal pleura, and overlying muscle were incised longitudinally. All procedures were successfully completed without conversion to open surgery. No abnormalities were detected in the esophageal mucosa. The median operating time was 60 minutes (range, 40-90 minutes). Postoperative histopathology confirmed leiomyoma in all patients. The median postoperative hospital stay was 6 days (range, 5-7 days). No major complications, such as esophageal leakage or esophageal diverticulum, occurred. Endoscopic methylene blue staining is safe and feasible for localizing small esophageal leiomyomas during thoracoscopic enucleation. This method will enable precise and easy enucleation. PMID- 26542839 TI - Actinomadura algeriensis sp. nov., an actinobacterium isolated from Saharan soil. AB - During the course of a screening programme for new taxa of actinobacteria, a strain designated ACD1(T), was isolated from a Saharan soil in the Hoggar region (Algeria). The taxonomic position of this strain was determined using a polyphasic taxonomic approach. The strain was observed to form extensively branched, non-fragmenting substrate mycelium, and aerial mycelium with straight to flexuous, hooked and irregular spirals (1-2 turns) forming short chains of spores. The diamino acid present in the cell wall is meso-diaminopimelic acid. Galactose, glucose, madurose, mannose and ribose occur in whole-cell hydrolysates. The diagnostic phospholipids detected were diphosphatidylglycerol and phosphatidylinositol. The major menaquinones were identified as MK-9 (H4) and MK-9 (H2). The major fatty acids were found to be C16:0, C18:1 cis9, iso-C16:0 and 10-methyl C18:0. Phylogenetic analysis based on the 16S rRNA gene showed that the strain belongs to the genus Actinomadura, and is closely related to Actinomadura sediminis DSM 45500(T) (98.5 % similarity) and Actinomadura cremea subsp. cremea DSM 43676(T) (98.3 % similarity). However, DNA-DNA hybridization revealed only 48.0 % relatedness with A. sediminis DSM 45500(T) and 33.2 % relatedness with A. cremea subsp. cremea DSM 43676(T). The combined phenotypic and genotypic data showed that the strain represents a novel species of the genus Actinomadura, for which the name Actinomadura algeriensis sp. nov. is proposed, with the type strain ACD1(T) (= DSM 46744(T) = CECT 8841(T)). PMID- 26542840 TI - PacBio Sequencing and Its Applications. AB - Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing (SGS) technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation (SV) in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with diseases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Additionally, PacBio's sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone. PMID- 26542841 TI - Development of a biomaterial associated with mesenchymal stem cells and keratinocytes for use as a skin substitute. AB - AIM: The present study has aimed to produce a cutaneous substitute, bringing together stem cells (mesenchymal stem cells) and keratinocytes, and an electrospun biomaterial. MATERIALS & METHODS: Three groups of scaffolds were studied: group 1, poly-dl-lactic acid (PDLLA); group 2, hydrolyzed PDLLA (PDLLA/NaOH) and group 3, PDLLA/Lam - a PDLLA/NaOH scaffold linked to laminin protein. They were characterized by physicochemical and biological parameters. RESULTS: As a result, the scaffolds presented well-formed and randomly distributed fibers. Group 3 showed the greatest hydrophilic characteristics. Group 1 showed a greater degradation rate after 14 days. Groups 2 and 3 presented molecular weight of about 40-50 Da. In general, group 3 showed the best results concerning cell adhesion and viability. CONCLUSION: This study associated two revolutionary fields, stem cells and nanotechnology, for use in regenerative medicine. PMID- 26542842 TI - Selection on pollen and pistil traits during pollen competition is affected by both sexual conflict and mixed mating in a self-compatible herb. AB - PREMISE OF THE STUDY: Although much attention has focused on the diversity of plant mating systems, only a few studies have considered the joint effects of mating system and sexual conflict in plant evolution. In mixed-mating Collinsia heterophylla, a sexual conflict over timing of stigma receptivity is proposed: pollen with a capacity to induce early onset of stigma receptivity secures paternity for early-arriving pollen (at the expense of reduced maternal seed set), whereas late onset of stigma receptivity mitigates the negative effects of early-arriving pollen. Here we investigated whether selection on pollen and pistil traits involved in sexual conflict is affected by the presence of both outcross- and self-pollen (mixed mating) during pollen competition. METHODS: We conducted two-donor crosses at different floral developmental stages to explore male fitness (siring ability) and female fitness (seed set) in relation to male and female identity, pollen and pistil traits, and type of competitor pollen (outcross vs. self). KEY RESULTS: Late-fertilizing pollen rather than rapidly growing pollen tubes was most successful in terms of siring success, especially in competition with self-pollen after pollination at early floral stages. Late stigma receptivity increased seed set after early-stage pollinations, in agreement with selection against antagonistic pollen. CONCLUSIONS: Selection on pollen and pistil traits in C. heterophylla is affected by both sexual conflict and mixed mating, suggesting the importance of jointly considering these factors in plant evolution. PMID- 26542843 TI - Shifts in diversification rates linked to biogeographic movement into new areas: An example of a recent radiation in the Andes. AB - PREMISE OF THE STUDY: Clade-specific bursts in diversification are often associated with the evolution of key innovations. However, in groups with no obvious morphological innovations, observed upticks in diversification rates have also been attributed to the colonization of a new geographic environment. In this study, we explore the systematics, diversification dynamics, and historical biogeography of the plant clade Rhinantheae in the Orobanchaceae, with a special focus on the Andean clade of the genus Bartsia. METHODS: We sampled taxa from across Rhinantheae, including a representative sample of Andean Bartsia species. Using standard phylogenetic methods, we reconstructed evolutionary relationships, inferred divergence times among the clades of Rhinantheae, elucidated their biogeographic history, and investigated diversification dynamics. KEY RESULTS: We confirmed that the South American Bartsia species form a highly supported monophyletic group. The median crown age of Rhinantheae was determined to be ca. 30 Myr, and Europe played an important role in the biogeographic history of the lineages. South America was first reconstructed in the biogeographic analyses around 9 Myr ago, and with a median age of 2.59 Myr, this clade shows a significant uptick in diversification. CONCLUSIONS: Increased net diversification of the South American clade corresponds to biogeographic movement into the New World. This movement happened at a time when the Andes were reaching the necessary elevation to host an alpine environment. Although a specific route could not be identified with certainty, we provide plausible hypotheses to how the group colonized the New World. PMID- 26542844 TI - Potential impacts of tolerance to herbivory on population dynamics of a monocarpic herb. AB - PREMISE OF THE STUDY: Mammalian herbivores, particularly white-tailed deer, can have a major impact on plant abundance and distribution. However, plants can tolerate herbivory by increasing seed production or seed quality. We used the monocarpic perennial Prenanthes roanensis to examine tolerance to mammalian herbivory through seed quality and modeled the effects of tolerance on population growth rate. METHODS: We examined seed quality (proportion of viable seeds, seed mass, germination, and seedling size) on damaged and undamaged plants to determine the extent to which plants tolerate herbivory. We then varied seed quality parameters over a range of values in population models to compare population growth rates under "no-tolerance" conditions (herbivory, but no tolerance) to those under "tolerance" conditions. KEY RESULTS: In most populations, plants damaged by herbivores had a greater proportion of viable seeds per plant or a greater probability of seed germination. Incorporating observed tolerance into population models did not significantly increase population growth rate. However, at low germination rates, increased germination of seeds from damaged plants has the potential to significantly increase population growth rate. CONCLUSIONS: Damaged plants can compensate for loss of reproductive heads by increasing seed viability and germination rates in the remaining seeds. This study is one of the first to demonstrate that tolerance through seed quality has the potential to affect population growth rate. Our results suggest that incorporating tolerance into population models may help elucidate mechanisms by which plant populations persist despite herbivory. PMID- 26542845 TI - Exploring the fossil history of pleurocarpous mosses: Tricostaceae fam. nov. from the Cretaceous of Vancouver Island, Canada. AB - PREMISE OF THE STUDY: Mosses, very diverse in modern ecosystems, are currently underrepresented in the fossil record. For the pre-Cenozoic, fossil mosses are known almost exclusively from compression fossils, while anatomical preservation, which is much more taxonomically informative, is rare. The Lower Cretaceous of Vancouver Island (British Columbia, Canada) hosts a diverse anatomically preserved flora at Apple Bay. While the vascular plant component of the Apple Bay flora has received much attention, the numerous bryophytes identified at the locality have yet to be characterized. METHODS: Fossil moss gametophytes in more than 20 carbonate concretions collected from the Apple Bay locality on Vancouver Island were studied in serial sections prepared using the cellulose acetate peel technique. KEY RESULTS: We describe Tricosta plicata gen. et sp. nov., a pleurocarpous moss with much-branched gametophytes, tricostate plicate leaves, rhizoid-bearing bases, and delicate gametangia (antheridia and archegonia) borne on specialized branches. A new family of hypnanaean mosses, Tricostaceae fam. nov., is recognized based on the novel combination of characters of T. plicata. CONCLUSIONS: Tricosta plicata reveals pleurocarpous moss diversity unaccounted for in extant floras. This new moss adds the first bryophyte component to an already diverse assemblage of vascular plants described from the Early Cretaceous at Apple Bay and, as the oldest representative of the Hypnanae, provides a hard minimum age for the group (136 Ma). PMID- 26542846 TI - Resolving cryptic species of Bossiella (Corallinales, Rhodophyta) using contemporary and historical DNA. AB - PREMISE OF THE STUDY: Phenotypic plasticity and convergent evolution have long complicated traditional morphological taxonomy. Fortunately, DNA sequences provide an additional basis for comparison, independent of morphology. Most importantly, by obtaining DNA sequences from historical type specimens, we are now able to unequivocally match species names to genetic groups, often with surprising results. METHODS: We used an integrative taxonomic approach to identify and describe Northeast Pacific pinnately branched species in the red algal coralline genus Bossiella, for which traditional taxonomy recognized only one species, the generitype, Bossiella plumosa. We analyzed DNA sequences from historical type specimens and modern topotype specimens to assign species names and to identify genetic groups that were different and that required new names. Our molecular taxonomic assessment was followed by a detailed morphometric analysis of each species. KEY RESULTS: Our study of B. plumosa revealed seven pinnately branched Bossiella species. Three species, B. frondescens, B. frondifera, and B. plumosa, were assigned names based on sequences from type specimens. The remaining four species, B. hakaiensis, B. manzae, B. reptans, and B. montereyensis, were described as new to science. In most cases, there was significant overlap of morphological characteristics among species. CONCLUSIONS: This study underscores the pitfalls of relying upon morpho-anatomy alone to distinguish species and highlights our likely underestimation of species worldwide. Our integrative taxonomic approach can serve as a model for resolving the taxonomy of other plant and algal genera. PMID- 26542847 TI - Multiple glacial refugia lead to genetic structuring and the potential for reproductive isolation in a herbaceous plant. AB - PREMISE OF THE STUDY: Glacial cycles have influenced the genetic structure of many species. In addition to facilitating genetic divergence, isolation in multiple glacial refugia may have contributed to the development of genetic incompatibility and reproductive isolation. We examined the phylogeography of Campanulastrum americanum, a monocarpic herbaceous plant that exhibits strong intraspecific reproductive isolation, to determine whether the current genetic structure reflects a history of multiple glacial refugia. METHODS: Chloroplast loci and nuclear RAD sequencing were used to characterize the range-wide phylogeography of C. americanum, in order to determine locations of potential glacial refugia and recolonization routes. Potential locations of refugia during the Last Glacial Maximum were also identified using ecological niche modeling. KEY RESULTS: Together, the chloroplast and nuclear phylogenies found support for three geographically structured, genetically divergent lineages, among which gene flow appears to be restricted. The distribution of these lineages indicates that C. americanum survived the Last Glacial Maximum in at least three refugia located in the Appalachians and on the Atlantic and Gulf coasts. The ecological niche model also supported the existence of multiple refugia. CONCLUSIONS: The isolation of populations of C. americanum in multiple refugia has led to a degree of phylogeographic structure greater than that found in most previously studied plants in eastern North America, which may be attributable to its short generation time. Reproductively isolated populations of C. americanum belong to divergent lineages, which suggests that survival in multiple glacial refugia contributed to the development of reproductive isolation in this species. PMID- 26542848 TI - Postzygotic barriers isolate sympatric species of Cyrtandra (Gesneriaceae) in Hawaiian montane forest understories. AB - PREMISE OF THE STUDY: Recent reviews of reproductive isolation (RI) in plants propose that boundaries between closely related species are maintained predominantly through prezygotic mechanisms. However, few experimental studies have explored how boundaries are maintained in long-lived species. Hawaiian Cyrtandra presents an intriguing challenge to our understanding of RI, as it comprises 60 shrub or small tree species that are almost exclusively restricted to wet forests, where sympatry of multiple species is common. METHODS: We assessed the relative strengths of pre- and postzygotic barriers among four species of Cyrtandra occurring at the extremes of the main Hawaiian Island's natural island-age gradient, Kaua'i (4.7 Myr) and Hawai'i Island (0.6 Myr), to contrast the strengths and stages of reproductive isolation among species at different stages of divergence. KEY RESULTS: A combination of F1 seed germination, F1 seedling survival, and F1 seedling growth isolated (61-91%) three of the species from sympatric relatives. In contrast, the fourth species was isolated (59%) from its sympatric relative through phenological differences alone. Significant postzygotic barriers in between-island crosses were also observed in one species. CONCLUSIONS: Results suggest that boundaries between sympatric Cyrtandra species in Hawaii are maintained predominantly through postzygotic barriers. Observations from between-island crosses indicate that postzygotic barriers can arise in allopatry, which may be important in the initial divergence of populations. Future studies of RI in Cyrtandra should include a broader range of species to determine if postzygotic isolating barriers are foremost in the maintenance of species boundaries in this large genus. PMID- 26542849 TI - Tumor antigens in human cancer control. AB - The body of evidence that is supporting the role of T cells in human tumor control is substantial and it is now beyond doubt that T cells can be crucial in the clinical response to cancer immunotherapies such as adoptive T cell therapy and checkpoint blockade. This has been proven in particular for melanoma and non small cell lung cancer. Strikingly, while clinical experience with these therapies is extensive, what these T cells detect on the tumors remains largely unknown. An extensive effort has been put into the characterization of tumor antigens and based on the recent successes of immunotherapies Cancer/Germline, mutated and viral antigens appear rather promising targets for tumor control. Furthermore, it is becoming evident that the most potent antigen in tumor control is highly dependent on the type of malignancy and may also vary even within malignancies. PMID- 26542850 TI - Association between low-grade albuminuria and hearing impairment in a non diabetic Korean population: The Korea National Health and Nutrition Examination Survey (2011-2013). AB - INTRODUCTION: The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. MATERIALS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study if they were younger than 19 years old, or had urine albumin/creatinine ratio (UACR) >= 30 mg/g or diabetes mellitus. There were 10,608 participants included in this study. The participants were divided into three groups according to their UACR tertiles. RESULTS: There were 1560; 1561; and 1552 male and 1982; 1975; and 1978, female participants in the low, middle, and high tertile groups, respectively. The results indicated the association between low-grade albuminuria and the numbers of metabolic syndrome (MetS) components or Framingham risk score, and the presence of MetS or the proportions of participants at high cardiovascular risk. Univariate and multivariate linear regression analyses demonstrated an association between the UACR and average hearing threshold (AHT) that was observed in both sexes. Multivariate analyses showed that mean AHTs in the low, middle, and high tertile groups were, respectively, 16.127 dB, 17.139 dB, and 18.604 dB for men, and 14.842 dB, 15.100 dB, and 16.353 dB, respectively, for women. Low-frequency, mid-frequency, and high-frequency hearing thresholds according to UACR tertiles showed similar trends. In both sexes, multivariate logistic regression analyses revealed that participants in the low and middle tertile groups had a decreased risk for hearing loss compared to participants in the high tertile group. CONCLUSION: Low grade albuminuria was associated with hearing impairment in the non-diabetic participants of this study. PMID- 26542851 TI - Erratum to: An Endoscopic Strategy Combining Mega Stents and Over-The-Scope Clips for the Management of Post-Bariatric Surgery Leaks and Fistulas (with video). PMID- 26542852 TI - Current concepts and innovations in trauma care: The German perspective. PMID- 26542854 TI - Bacterial contamination of open fractures - pathogens, antibiotic resistances and therapeutic regimes in four hospitals of the trauma network Cologne, Germany. AB - INTRODUCTION: The bacterial contamination of soft tissues and bone in open fractures leads to an infection rate of up to 50%. Pathogens and their resistance against therapeutic agents change with time and vary in different regions. In this work, our aims were to characterize the bacterial spectrum present in open fractures, analyze the bacterial resistance to antibiotic agents and question the EAST guideline recommendations for antibiotic prophylaxis after open fractures in a German Trauma Network. MATERIALS AND METHODS: We conducted a retrospective cohort study and included all patients with open fractures from 1(st) of January 2011 until the 31(st) of December 2014 in four hospitals of the trauma network cologne. Soft tissue damage was classified according to the Gustilo Anderson classification. RESULTS: We included 123 patients. Forty-five injuries (37%) were classified I degrees , 45 (37%) as II degrees and 33 (27%) as III degrees . Lower leg (34%) was the most commonly injured location. An antibiotic prophylaxis was administered to 109 patients (89%). In 107 of them (98%) a cephalosporin or cephalosporin combination was given. In 35 of the patients (28%), microbiological samples were taken of the fracture site. Wound cultures were positive in 21 patients (60%). Fifty percent of the bacterial detections occurred in III degrees fractures. Coagulase negative Staphylococci (COST) were the most frequent pathogens. In II degrees open fractures one gram-negative strain was isolated. Fewest resistances were seen against quinolones and co-trimoxazole. DISCUSSION: The recommended EAST guideline prophylaxis would have covered all but one bacterium (97% of positive cultures). One Escherichia coli was found in a II degrees open fracture and would have been missed. One of the isolated Staphylococci epidermidis and an Enterococcus faecium were resistant against gentamycin and first- and second-generation-cephalosporin's which were used as prophylaxis frequently. However, a regional adaption of the EAST guidelines seems not justified due to the rather low number of cases in our study. CONCLUSION: The EAST guideline seems to be adequate in a high percentage of cases (97%) in the setting of the trauma network cologne. Further research should be guided at identification of initial open fracture pathogens to improve the efficiency of antibiotic prophylaxis. PMID- 26542853 TI - Isolated pediatric radial head and neck fractures. A rare injury. Analysis and follow up of 19 patients. AB - PURPOSE: Isolated pediatric radial head and neck fractures are rare. In recent literature, their incidence is estimated to be around 1% of all fractures. High rates of complications are reported. Beside non-operative treatment, head fractures are treated with k-wires, mini-screws or polypins, whereas neck fractures are treated more and more with elastic stable intramedullary nailing (ESIN). Purpose of the study was to evaluate the operative management, complications and clinical outcomes of these injuries. METHODS: Retrospective analysis between 2002 and 2014. 19 children with isolated radial head and neck fractures were treated in our institution. Age averaged 11 years (range 6-16). Operative treatment with elastic stable intramedullary nailing (ESIN) was performed in 13 patients, in one patient with an additional k-wire; two screw, two k-wire and one polypin fixation was performed in the others. One child was treated non-operatively. RESULTS: Follow up averaged 19 months (2-89). Initial complications occurred in nine children such as fracture dislocation (1), nonunion (1), malunion (1), elbow ankylosis (1), infection (1), crossunion (2), intraarticular screw penetration (1) and radial nerve irritation (1). ESIN lead a complication rate of 36%, mini-screw fixation and k-wire fixation showed a complication rate of 100%. All children (100%) with an open reduction maneuver and 36% children with closed or percutaneous reduction developed a complication. Secondary surgeries included ESIN removal and k-wire fixation (1), open arthrolysis (1), debridement (1), removal of crossunion (1), radial head removal plus arthrolysis (3) and screw removal (1). Subsequently 74% (14) children showed a free or <20 degrees limited range of motion on final follow up. Implant removal was performed after an average of 8 weeks (5-12). Three patients were transferred to our surgical department after a complication following initial treatment. Excluding these, an overall complication rate of 37.5% was noted. CONCLUSIONS: Radial head injuries in children are rare. In this population, neck fractures occur more frequently. If conservative treatment is not possible, ESIN seems to be a simple and protective procedure for neck fractures; polypins or screws can be used for complicated radial head fractures. Complications occur frequently after open reduction. If closed reduction and internal fixation is possible, range of motion can be completely restored. PMID- 26542855 TI - Size matters: The influence of the posterior fragment on patient outcomes in trimalleolar ankle fractures. AB - INTRODUCTION: Ankle fractures are increasing in incidence. The more complicated the lesion is, the higher the risk of developing posttraumatic arthrosis. Severe posttraumatic arthrosis results in a reduced quality of life. Therefore, the treatment of a trimalleolar fractures is crucial. However, the treatment guidelines for posterior malleolar fractures (PMF) are still based on recommendations from 1940. Only a few retrospective studies have been conducted, which analysed patient outcomes based on lateral X-rays of the ankle. The purpose of this retrospective analysis was to survey patient outcomes in relation to the size of the PMF on the basis of CT-scans. METHODS: We retrospectively examined 42 patients with trimalleolar fractures with an average follow-up of 2.5 years. Twenty-four patients (57%) received a CT scan of the ankle joint. The radiologic images were analysed for the size of the PMF and the involvement of the joint surface using lateral X-rays and available CT images. We examined all 42 patients clinically and radiologically, and estimated the grade of arthrosis of the ankle in accordance with the Bargon Score and assigned AOFAS Scores for each patient. We divided our patients into different groups according to the size of their PMF and evaluated patient outcomes in accordance with the compiled data first on the basis of X-ray data and then on the basis of CT data. RESULTS: Comparing the measurement results by two different radiologic methods revealed that CT results in a more precise determination of PMF size in contrast to lateral X-rays, by which measurements were generally overrated. The statistical evaluation of our data demonstrated that patients with an osteosynthesis of the PMF and a PMF size of >25% showed signs of posttraumatic arthrosis but had better outcomes in accordance to the AOFAS score. All results were not significant. CONCLUSION: An exact evaluation of CT images of posterior malleolar fractures in patients with trimalleolar ankle fractures is crucial for the decision to perform an osteosynthesis of the PMF and, therefore, an analysis of patient outcomes. The results of previous studies should be evaluated cautiously due to missing CT data. To date, this is the largest retrospective patient series of patient outcomes based on CT data. PMID- 26542856 TI - The cement-augmented transiliacal internal fixator (caTIFI): an innovative surgical technique for stabilization of fragility fractures of the pelvis. AB - INTRODUCTION: Analyzing the different age groups in a population who suffered a pelvic ring fracture it becomes obvious that there are important differences between the pelvic ring lesions of an elderly patient compared to a young adult concerning trauma mechanism, fracture pattern and therapeutic options. In the elderly patient it is very important to achieve maximum of stability if surgery is necessary in order to avoid early failure of the ostheosynthesis under mobilization with full weight bearing. PATIENTS AND METHODS: 15 patients (14 female) with fragility fractures of the pelvis that required surgical stabilization were eligible to participate in this study from December 2012 to December 2014. Such details were documented and analysed as patient demographics, mechanism of injury, fracture classification, operative treatment and postoperative radiological parameters of achieved bone-implant interface. RESULTS: The average age of the patients was 79.9 years (SD 9.0 years). According to Rommens five patients had a fragility fracture of the pelvis Type II-c, one a Type III-c, six a Type IV-b and three a Type IV-c. Four patients were treated by a cement augmented transiliac internal fixation (caTIFI). Seven patients received a cement augmented iliolumbar fixation. In all these patients the Schanz screws applied to the ilium were placed in an oblique dorsoventral direction into the supraacetabular bone canal (mean length of screws 100 +/- 20mm, max. 135 mm, min. 70 mm). Even though in four patients the iliosacral joint was hit tangential and one cortex perforation without any cement leakage appeared no revision surgery was necessary. Overall the clinical findings including mobilisation with full weight bearing showed a sufficient mechanically stability in all patients. CONCLUSION: The focus of this study was to describe the modified surgical technique of the caTIFI with placing the Schanz screws from the posterior superior iliac spine to the anterior inferior iliac spine into the supraacetabular bone canal. Usage of cannulated and perforated Schanz screws gives the opportunity to control the correct position of the screws before implanting them. Another advantage is that additional stability can be obtained by cement augmentation. We believe that the new technique of the caTIFI provides a greater intraoperative versatility and a greater mechanical stability for fragility fractures of the pelvis. PMID- 26542857 TI - Reconstruction of septic diaphyseal bone defects with the induced membrane technique. AB - Septic segmental bone voids of the diaphysis are difficult to manage. The induced membrane technique by Masquelet has been successfully used to reconstruct segmental defects more than 20 cm. Our article describes a series of 13 cases with extensive posttraumatic bone loss of the metatarsal, tibial, femoral and radial bones after septic injuries followed by multiple surgical interventions. Antibiotic-impregnated polymethyl methacrylate (PMMA) cement spacers were implanted after successful eradication of bacterial infections of soft tissue and bones. After a mean of 9.8 weeks, body-induced membranes were established and the cements spacers removed. To fill up the bone void, cancellous bone autografts were implanted into the membranes. The follow-up examination after 24 months revealed bony union in all cases and favorable functional results. The induced membrane technique has shown to be effective in treating bone defects of upper and lower extremity bone defects. PMID- 26542858 TI - PMMA-augmented SI screw: a biomechanical analysis of stiffness and pull-out force in a matched paired human cadaveric model. AB - INTRODUCTION: Current literature data and clinical experience show that the number of pelvic fractures continuously rises due to the increasing elderly population. In the elderly with suspected osteoporosis additional implant augmentation with bone cement seems to be an option to avoid secondary displacement. There are no reported biomechanical data in the literature comparing the fixation strength (and anchorage) of standard and augmented SI screws so far. The purpose of this study was to assess the biomechanical performance of cement-augmented versus non-augmented SI screws in a human cadaveric pelvis model. MATERIAL AND METHODS: Six human cadaveric pelvises preserved with the method of Thiel were used in this study. Each pelvis was split to a pair of 2 hemi-pelvises, assigned to 2 different groups for instrumentation with one non-augmented or one contralateral cement-augmented SI screw, placed in the body of S1 in a randomized fashion. The osteosynthesis followed a standard procedure with 3D controlled percutaneous iliosacral screw positioning. A biomechanical setup for a quasistatic pullout test of each SI screw was used. Construct stiffness and maximum pullout force were calculated from the load displacement curve of the machine data. Statistical evaluation was performed at a level of significance p = .05 for all statistical tests. RESULTS: Stiffness and pullout force in the augmented group (501.6 N/mm +/- 123.7, 1336.8 N +/- 221.1) were significantly higher than in the non-augmented one (289.7 N/mm +/- 97.1, 597.7 N +/- 115.5), p = .04 and p = .014, respectively. BMD influenced significantly the pullout force in all study groups. CONCLUSION: Cement augmentation significantly increased the fixation strength in iliosacral screw osteosynthesis of the sacrum in a biomechanical human cadaveric model. PMID- 26542859 TI - One year orthopaedic trauma experience using an advanced interdisciplinary hybrid operating room. AB - Hybrid operating rooms have been used successfully in several surgical specialties, but no data have been published for orthopaedic trauma. We present our one-year orthopaedic trauma experience using a hybrid operating room, which incorporates 3D fluoroscopic imaging as well as navigation capabilities. Data were compiled for a series of 92 cases performed in an advanced hybrid operating room at the level one trauma center in Ulm, Germany. All patients who had surgery performed using this operating room during the first year were included. Setup time and surgical complications using hybrid operating room were recorded and analysed. The hybrid operating room resulted in no higher rate of complication than expected from the same cases in a conventional operating room. The hybrid room did however allow the surgeon to confidently place implants for orthopaedic trauma cases, and was most advantageous for spine and pelvis cases, both minimally invasive and conventional. Further, appropriate reduction and implant position was confirmed with 3D imaging prior to leaving the operating room and obviated the need for postoperative CT scan. Based on our one-year experience, the hybrid operating room is a useful and safe tool for orthopaedic trauma surgery. PMID- 26542860 TI - Decrease of morbidity in road traffic accidents in a high income country - an analysis of 24,405 accidents in a 21 year period. AB - BACKGROUND: The WHO initiated the "Decade of Action for Road Safety" because the fatality on road traffic accidents could become the fifth leading cause of death in 2030. On the contrary, fatalities continue to decrease in high income countries. The aim of the study was to find evidence for changes in injury severity of passenger car occupants after road traffic accidents in Germany over time, and to find contributing factors. METHODS: Data from the German In Depth Accident Study (GIDAS), representative for Germany, was used. A total of 24.405 accidents, reported from 1991 until 2011. 44.503 adult passenger car occupants were examined. A multivariable logistic regression model was developed to find reasons for observed trends over time. RESULTS: The relative decrease in mortality was 68.8% from 1991 until 2011. Between 2006 and 2011, the percentage of severely injured traffic victims was less than half, both in terms of the whole body and individual body regions. For injuries with an Abbreviated Injury Scale (AIS) >= 2, the percentage of persons with lower leg injuries declined by 72.5%, followed by the percentage of persons with pelvic injuries (61.5%), upper extremity injuries (57.7%), head injuries (54.3%), thorax injuries (50.0%), and abdomen injuries (40.0%). The multivariable regression model found 13 independent variables associated with injury prevention (e.g. seat belt use: OR 0.41, CI 95% 0.32-0.49; airbag: OR 0.86, CI 95% 0.75-0.99). The implementation of protective factors increased over time while accident constellations with a high probability for severe injury decreased over time. CONCLUSION: The decrease of severe injuries after road traffic accidents can be only attributed to a comprehensive approach including the enforcement of road safety policies and innovations in car engineering and emergency medicine. Traffic related measures and alcohol level control, and seat belt usage enforcement next to other technical advances are considered especially important. PMID- 26542861 TI - The standardized creation of a lumbar spine vertebral compression fracture in a sheep osteoporosis model induced by ovariectomy, corticosteroid therapy and calcium/phosphorus/vitamin D-deficient diet. AB - INTRODUCTION: Vertebral compression fractures (VCFs) are one of the most common injuries in the aging population presenting with an annual incidence of 1.4 million new cases in Europe. Current treatment strategies focus on cement associated solutions (kyphoplasty/vertebroplasty techniques). Specific cement associated problems as leakage, embolism and the adjacent fracture disease are reported adding to open questions like general fracture healing properties of the osteoporotic spine. In order to analyze those queries animal models are of great interest; however, both technical difficulties in the induction of experimental osteoporosis in animal as well as the lack of a standardized fracture model impede current and future in vivo studies. This study introduces a standardized animal model of an osteoporotic VCF type A3.1 that may enable further in-depth analysis of the afore mentioned topics. MATERIAL AND METHODS: Twenty-four 5-year old female Merino sheep (mean body weight: 67 kg; range 57-79) were ovariectomized (OP1) and underwent 5.5 months of weekly corticosteroid injections (dexamethasone and dexamethasone-sodium-phosphate), adding to a calcium/phosphorus/vitamin D-deficient diet. Osteoporosis induction was documented by pQCT and micro-CT BMD (bone mineral density) as well as 3D histomorphometric analysis postoperatively of the sheep distal radius and spine. Non osteoporotic sheep served as controls. Induction of a VCF of the second lumbar vertebra was performed via a mini-lumbotomy surgical approach with a standardized manual compression mode (OP2). RESULTS: PQCT analysis revealed osteoporosis of the distal radius with significantly reduced BMD values (0.19 g/cm(3), range 0.13-0.22 vs. 0.27 g/cm(3), range 0.23-0.32). Micro-CT documented significant lowering of BMD values for the second lumbar vertebrae (0.11 g/cm(3), range 0.10-0.12) in comparison to the control group (0.14 g/cm(3), range 0.12 0.17). An incomplete burst fracture type A3.1 was achieved in all cases and resulted in a significant decrease in body angle and vertebral height (KA 4.9 degrees , range: 2-12; SI 4.5%, range: 2-12). With OP1, one minor complication (lesion of small bowel) occurred, while no complications occurred with OP2. CONCLUSIONS: A suitable spinal fracture model for creation of VCFs in osteoporotic sheep was developed. The technique may promote the development of improved surgical solutions for VCF treatment in the experimental and clinical setting. PMID- 26542863 TI - Semi-rigid screws provide an auxiliary option to plate working length to control interfragmentary movement in locking plate fixation at the distal femur. AB - BACKGROUND: Extent and orientation of interfragmentary movement (IFM) are crucially affecting course and quality of fracture healing. The effect of different configurations for implant fixation on successful fracture healing remain unclear. We hypothesize that screw type and configuration of locking plate fixation profoundly influences stiffness and IFM for a given load in a distal femur fracture model. METHODS: Simple analytical models are presented to elucidate the influence of fixation configuration on construct stiffness. Models were refined with a consistent single-patient-data-set to create finite-element femur models. Locking plate fixation of a distal femoral 10mm-osteotomy (comminution model) was fitted with rigid locking screws (rLS) or semi-rigid locking screws (sLS). Systematic variations of screw placements in the proximal fragment were tested. IFM was quantitatively assessed and compared for different screw placements and screw types. RESULTS: Different screw allocations significantly affect IFM in a locking plate construct. LS placement of the first screw proximal to the fracture (plate working length, PWL) has a significant effect on axial IFM (p < 0.001). Replacing rLS with sLS caused an increase (p < 0.001) of IFM under the plate (cis-cortex) between +8.4% and +28.1% for the tested configurations but remained constant medially (<1.1%, trans-cortex). Resultant shear movements markedly increased at fracture level (p < 0.001) to the extent that plate working length increased. The ratio of shear/axial IFM was found to enhance for longer PWL. sLS versus rLS lead to significantly smaller ratios of shear/axial IFM at the cis-cortex for PWL of >= 62 mm (p <= 0.003). CONCLUSION: Mechanical frame conditions can be significantly influenced by type and placement of the screws in locking plate osteosynthesis of the distal femur. By varying plate working length stiffness and IFM are modulated. Moderate axial and concomitantly low shear IFM could not be achieved through changes in screw placement alone. In the present transverse osteotomy model, ratio of shear/axial IFM with simultaneous moderate axial IFM is optimized by the use of appropriate plate working length of about 42-62 mm. Fixation with sLS demonstrated significantly more axial IFM underneath the plate and may further contribute to compensation of asymmetric straining. PMID- 26542862 TI - Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation. AB - INTRODUCTION: Since the first description of autologous chondrocyte implantation (ACI) in 1994 different methods and improvements were established for this regenerative treatment option of large chondral defects. This study analyzes safety and short-term clinical results from characterized ACI using a collagen based biphasic scaffold and evaluates prognostic factors. METHODS: 433 patients with a mean age of 33.4 years and localized grade III to IV cartilage defects (ICRS classification) in the knee or ankle were included. Mean defect size was 5.9 cm(2). Prior seeding of the scaffold, expanded chondrocytes were characterized by RT-PCR on 6 different marker genes (type I and II collagen, aggrecan, interleukin-1 beta (IL-1beta), vascular endothelial growth factor receptor 1 (FLT-1) and bone sialoprotein-2 (BSP-2)). Clinical outcome was evaluated using a questionnaire for defect history, basic demographics, time elapsed from surgery, 10-point outcome assessments of pain, function and swelling. Moreover, adverse events (AEs) or subsequent treatments were recorded and analysed. RESULTS: Patients improved significantly over baseline (p < 0.0001) in pain, function and swelling. Subjects with later than 12 months follow-up reported nominally greater mean changes. Graft failure incidence was 6% for patients with greater than one year follow-up. Graft-related complications were significantly higher for patellar (p < 0.0001) and degenerative defects (p = 0.005). Elevated expression of FLT-1 (p = 0.02) or IL-1 beta mRNA (p = 0.03) was associated with graft-related AEs. A borderline association was found for low collagen type II expression (p = 0.08). CONCLUSION: Early graft-related AEs after ACI with a biphasic collagen scaffold are related to defect type, location and marker gene expression. The levels of significance observed for gene expression with respect to graft-related AEs were subordinate to those identified in the analysis of lesion history and location. PMID- 26542864 TI - The role of angio-embolization in the acute treatment concept of severe pelvic ring injuries. AB - BACKGROUND: In recent years a wide variety of strategies to treat the haemodynamically unstable patient with pelvic ring fractures have been proposed. This study evaluates our institutional management of patients with severe pelvic fractures and analyses their outcomes. METHODS: Retrospective review of all severely injured trauma patients with pelvic ring injuries admitted to a level I trauma centre from 2007 to 2012. Patient records were documented prospectively in a trauma database and evaluation was performed by SPSS. RESULTS: During the study period, a total of 173 patients with pelvic ring fractures were admitted and formed the basis of this study. Overall, 46% of the patients had suffered a type A fracture, 25% a type B fracture and the remaining 29% a type C pelvic ring fracture. Surgical treatment was required in 21% of the patients (pelvic C-clamp, n = 6; supra-acetabular external fixator, n = 32; pelvic packing, n = 12; definitive plate osteosynthesis of the pubis symphysis, n = 6). Angio embolization was performed in 16 patients (9%); in 8 patients it was the only specific treatment for the pelvic injury on day 0 and in 8 patients it was performed immediately post-operatively. The overall mortality rate was 12.7% (n = 22), with the type C pelvic fractures having the highest mortality (30.0%). Four patients died immediately after admission in the shock room. CONCLUSIONS: Angiographic embolization as a first-line treatment was only performed in haemodynamically stable patients or in patients responding to fluid resuscitation with the finding of an arterial blush in the CT scan. In haemodynamically unstable patients, pre-peritoneal pelvic packing in combination with mechanical pelvic stabilization was immediately carried out, followed by angio-embolization post-operatively if signs of persistent bleeding remained present. PMID- 26542865 TI - Treatment of atrophic tibia non-unions according to 'diamond concept': Results of one- and two-step treatment. AB - BACKGROUND: The successful treatment of atrophic tibia non-unions and tibia non unions with large bone defects or infections is a major challenge in orthopedic and trauma surgery. This article evaluates the use of the 'diamond concept' using a one-step or two-step procedure according to 'Masquelet technique' in the treatment of atrophic tibia non-unions. METHODS: Between February 2010 and March 2014, 102 patients with atrophic non-unions were treated according to the 'diamond concept' in our center. Ninety-nine were available for follow-up. Forty nine received a one-step treatment (Group 1, G1) and 50 patients received a two step treatment according to the 'Masquelet technique' (Group 2, G2). Clinical and radiological parameters were measured preoperatively as well as 4, 6, and 12 weeks and 6 and 12 months postoperatively. In order to evaluate the subjective health of patients, we used the SF-12 questionnaire. Data analysis was performed one year after treatment. RESULTS: The rate of consolidation in G1 was 84% and 80% in G2. The time to heal in G2 was 8.6 +/- 2.9 months, which is significantly longer than in G1 being 6.9 +/- 3.1 months. In comparison patients in G1/G2 had an average of 3.2/6.7 previous major surgeries. In G1, 4 of 8 patients who did not heal successfully showed positive intraoperative cultures. In G2, 26 patients (52%) initially presented with positive cultures. The results of the SF-12 questionnaire improved in both groups during the postoperative follow-up, but showed no significant differences between groups. In 29 patients a gentamycin coated nail was used for reosteosynthesis. These patients showed by trend a lower rate of complications at a higher rate of consolidation. CONCLUSIONS: Our study showed that the 'diamond concept' is a suitable method for safely and effectively treating non-unions with large defects or infections. The use of an antibiotic coated nail provides a therapeutic benefit. For large bone defects of infected non-unions the two-step procedure after Masquelet is an efficient way to eradicate the infection and treat the bone defect successfully. PMID- 26542866 TI - Analysis of 213 currently used rehabilitation protocols in foot and ankle fractures. AB - INTRODUCTION: Fractures of the ankle, hind- and midfoot are amongst the five most common fractures. Besides initial operative or non-operative treatment, rehabilitation of the patients plays a crucial role for fracture union and long term functional outcome. Limited evidence is available with regard to what a rehabilitation regimen should include and what guidelines should be in place for the initial clinical course of these patients. This study therefore investigated the current rehabilitation concepts after fractures of the ankle, hind- and midfoot. METHODS: Written rehabilitation protocols provided by orthopedic and trauma surgery institutions in terms of recommendations for weight bearing, range of motion (ROM), physiotherapy and choice of orthosis were screened and analysed. All protocols for lateral ankle fractures type AO 44A1, AO 44B1 and AO 44C1, for calcaneal fractures and fractures of the metatarsal as well as other not specific were included. Descriptive analysis was carried out and statistical analysis applied where appropriate. RESULTS: 209 rehabilitation protocols for ankle fractures type AO 44B1 and AO 44C1, 98 for AO 44A1, 193 for metatarsal fractures, 142 for calcaneal fractures, 107 for 5(th) metatarsal base fractures and 70 for 5(th) metatarsal Jones fractures were evaluated. The mean time recommended for orthosis treatment was 6.04 (SD 0.04) weeks. While the majority of protocols showed a trend towards increased weight bearing and increased ROM over time, the best consensus was noted for weight bearing recommendations. CONCLUSION: Our study shows that there exists a huge variability in rehabilitation of fractures of the ankle-, hind- and midfoot. This may be contributed to a lack of consensus (e.g. missing publication of guidelines), individualized patient care (e.g. in fragility fractures) or lack of specialization. This study might serve as basis for prospective randomized controlled trials in order to optimize rehabilitation for these common fractures. PMID- 26542867 TI - Timing of surgery for open reduction and internal fixation of displaced proximal humeral fractures. AB - BACKGROUND: Open reduction and internal fixation is one established method for treatment of displaced fractures of the proximal humerus. However, the timing of surgery and its effect on complications have not yet been investigated in the literature. Hence, aim of this study was to analyze the occurrence of complication following locked plating of proximal humeral fractures when surgery was delayed in comparison to early intervention. METHODS: Between February 2002 and November 2010, 497 patients with displaced proximal humeral fractures were treated by open reduction and locked plating. 329 patients were available for follow-up with a minimum of 12 months after surgery. Outcome analysis included radiographic evidence of loss of fixation (> 10 degrees of secondary displacement), screw-cutout and avascular head necrosis. Outcomes were analyzed with regards to age, gender and fracture pattern and were compared between time intervals in which the primary surgery had been conducted; early intervention (< 48 h), timely scheduled for surgery (3-5 days) and delayed intervention (>5 days). RESULTS: Of 329 patients (68.4% women; median age at time of surgery: 69.9 years, 95% Confidence Interval (CI) 68.2, 71.2) the median time between fracture incident and surgical intervention was 3.2 days (95%CI: 3.1, 3.3). Surgery was performed in a 2-part fracture at a median of 3.3 days (95%CI: 3.2, 3.4) after trauma, in a 3-part fracture after 3.3 days (95%CI: 3.1, 3.4), in a 4-part fracture 2.9 days (95%CI: 2.8, 3.0), in head split type fracture 2.2 days (95%CI: 2.0, 2.4) and in dislocation type fracture 0.8 days after trauma (95%CI: 0.7, 0.9, p = 0.40). Loss of fixation was observed in 12.8% (n = 42 patients), of which in 4.9% (n = 16) screw cutout was evident and in 6.8% of cases (n = 20) avascular head necrosis was diagnosed. Patients in which complication was observed were treated at median 2.5 days after trauma (95% CI, 1.8, 3.2), in comparison, patients without evidence of complications were treated at a median of 3.2 days (95% CI, 2.8-3.8, p = 0.35). The odds ratio regarding occurrence of complications for patients treated <48 hours was 0,924, for patients in which surgery was performed 3-5 days after the incident the odds ratio was 0,836 and in patients treated > 5 days the odds ratio was 1,637. CONCLUSIONS: Loss of fixation following open reduction and internal fixation of proximal humeral fractures was not more frequently observed when surgery was performed 3-5 days after the incident in comparison to early intervention (< 48 h). However, a delay of intervention > 5 days is related to significant increase of complications. Thus, if open reduction and internal fixation is indicated, reconstruction of the proximal humerus should be performed within 5 days of the fracture event. In head split and dislocated fracture types anatomic reconstruction completed within 48 h from the incident may be beneficial with regards to risk of avascular necrosis. PMID- 26542868 TI - Reduction and retention of thoracolumbar fractures by minimally invasive stabilisation versus open posterior instrumentation. AB - PURPOSE: The purpose of this study was in thoracolumbar fractures to assess the effectiveness of minimal invasive stabilisation compared to the open technique with regards to the change in kyphosis angle, the loss of reduction and length of hospital stay. METHODS: The retrospective study consisted of 104 patients who received minimally invasive stabilisation or open stabilisation. Patients were between 15 and 86 years of age, had a thoracolumbar fracture and no neurological deficits. Kyphotic angle (Cobb angle) and loss of reduction was compared after minimal invasive and open stabilisation. The Cobb angle was evaluated directly post operatively, at 6 weeks, 3 months, 6 months and 12 months after surgery. RESULTS: Evaluated patients who received the minimally invasive technique had a shorter surgical intervention time and a shorter hospital stay compared to patients who received the open technique. Kyphosis angle and loss of reduction showed no significant difference compared to open technique. There was also no significant difference between minimally invasive poly-axial and mono-axial stabilisation. CONCLUSION: In this study we provide evidence that MIS instrumentation in selected thoracolumbar fractures can effectively be used without significant differences in loss of reduction compared to open stabilisation. MIS can also sufficiently retain reduction as compared to traditional open techniques. The main advantages are reduced operation time and shorter hospital stay. PMID- 26542869 TI - A novel electromagnetic navigation tool for acetabular surgery. AB - BACKGROUND: Acetabular fracture surgery is demanding and screw placement along narrow bony corridors remains challenging. It necessitates x-ray radiation for fluoroscopically assisted screw insertion. The purpose of this cadaver study was to evaluate the feasibility, accuracy and operation time of a novel electromagnetic navigation system for screw insertion along predefined acetabular corridors. METHODS: A controlled laboratory study with a total of 24 electromagnetically navigated screw insertions was performed on 8 cadaveric acetabula. 3 peri-acetabular bony corridors (QSS, Quadrilateral Surface Screw; IAS, Infra-Acetabular Screw; PCS, Posterior Column Screw) were defined and screws were placed in a defined order without fluoroscopy. Operation time was documented. Postoperative CT scans were performed to analyse accuracy of screw placement. RESULTS: Mean cadaver age was 70.4 +/- 11.7. Successful screw placement was accomplished in 22 out of 24 (91.7%) cases. The overall mean time for all 3 acetabular screws was 576.6 +/- 75.9s. All 3 complications occurred during the placement of the IAS due to an impassable narrow bony corridor. QSS mean length was 50 +/- 5mm, IAS mean length was 85 +/- 10mm and PCS mean length was 120 +/- 5mm. CONCLUSION: In this cadaver study the novel electromagnetic navigation system was feasible to allow accurate screw placement without fluoroscopy in defined narrow peri-acetabular bony corridors. PMID- 26542870 TI - Spinal fracture reduction with a minimal-invasive transpedicular Schanz Screw system: clinical and radiological one-year follow-up. AB - INTRODUCTION: Surgical management of thoracolumbar trauma involves correction of posttraumatic deformity and placement of transpedicular instrumentation. The aim of this prospective cohort study was to generate first results reflecting the clinical and radiological outcome of patients treated with percutaneous dorsal instrumentation for fractures of the thoracic and lumbar spine with the use of a transpedicular new Schanz Screw system (USS Fracture MIS, DePuy Synthes). METHODS: A total of 26 patients with fractures of the thoracic and lumbar spine were operatively treated with bi-segmental dorsal instrumentation between January and December 2012. Radiological data acquisition was performed pre- and postoperatively, after six weeks, three, six, and twelve months. The radiological parameter of interest was the bi-segmental kyphotic end plate angle (Cobb angle). The Chronic Disability Index (CDI), the Oswestry Disability Index (ODI), and the Spine Tango Core Outcome Measurement Index (COMI) were applied to investigate the clinical outcome. RESULTS: The clinical follow-up was completed by 22 patients (84.6%), and the radiological follow-up by 21 (80.8%) patients. Our patient population had a mean age of 47.4 +/- 4.1 years. Twelve patients received dorsal instrumentation, and 14 patients were treated with an additional ventral reconstruction. Intraoperative reduction was 11.5 +/- 1.5 degrees among all patients (p < 0.01). A considerable amount of the operative correction was lost after six weeks with a loss of reduction of 4.6 +/- 1.4 degrees (p < 0.01). At one year follow-up, the measured loss of reduction was significant in comparison to the postoperative state, 6.9 +/- 1.3 degrees among all patients, 8.7 +/- 2.1 degrees after dorsal and 4.9 +/- 1.1 degrees after dorsoventral stabilisation (all p < 0.01). Moreover, all patients had minimal to moderate disability with a CDI of 1.8 +/- 0.4 (0 - 7), and an ODI of 15.6 +/- 3.6 (0 - 60). CONCLUSION: The new transpedicular Schanz screw system can deliver a correction and stabilization of thoracic and lumbar spine fractures. Patients report minimal to moderate disability as a result of their severe injury one year after trauma. We advocate the use of the transpedicular Schanz screw system to correct posttraumatic kyphotic deformity, with secondary anterior fusion in our treatment strategy of thoracolumbar incomplete burst fractures in patients without a neurologic deficit. PMID- 26542871 TI - A novel locking screw hip stem to achieve immediate stability in total hip arthroplasty: A biomechanical study. AB - INTRODUCTION: As total hip arthroplasty is now applicable for younger, healthier, and more active patients, bone preservation becomes even more essential, and proximal fixation, resulting in less stress shielding, draws special attention with focus on new strategies and implant designs. Recently, a new type of non cemented fixation of the femoral component, featured with the locking screw hip (LSH) stem, was developed by Scyon Orthopaedics AG (Au-Waedenswil, Switzerland). The idea to rigidly fix the femoral component of a prosthesis for total hip replacement in this fashion evolved from the very good results achieved with the internal point-contact fixator PC-Fix. The purpose of this study was to investigate the unique characteristics of the LSH-stem and to assess its biomechanical performance in comparison to a conventional cemented prosthesis (Mueller straight stem). MATERIAL AND METHODS: Six paired human cadaveric femora were preserved with the method of Thiel, split in two study groups, implanted with either cemented Mueller straight stem or LSH-stem prostheses and biomechanically tested under progressively increasing axial loading until catastrophic failure. Bone mineral density (BMD) of all femora was evaluated in the femoral head prior to implantation. Axial construct stiffness, failure load and cycles to failure were calculated from the machine data and statistically evaluated at a level of significance p = 0.05. RESULTS: No statistically significant difference between the LSH-stem and the Mueller straight stem was found in terms of axial construct stiffness (2031.5 N/mm +/- 483.1 N/mm and 2403.6 N/mm +/- 705.2 N/mm, p = 0.115), failure load (4958.8 N +/- 1094.1 N and 5907.2 N +/- 1562.8 N, p = 0.138) and cycles to failure (7917.7 +/- 2188.1 and 9814.3 +/- 3125.6, p = 0.138). BMD showed no significant difference between the two study groups, p = 0.616. CONCLUSION: The LSH-stem seems to be stable enough to carry loads experienced during the rehabilitation period of a patient after THR. Its stability, which is similar to that of the Mueller straight stem, may justify the clinical application of the LSH-stem under thorough investigation. PMID- 26542873 TI - Development of a scoring system based on conventional parameters to assess polytrauma patients: PolyTrauma Grading Score (PTGS). AB - BACKGROUND: The impact of conventional laboratory data to identify polytrauma patients at risk of complications is established. However, it has not been assessed in terms of prognostic accuracy for systemic complications (ARDS, organ failure). We therefore assessed the most predictive parameters for systemic complications and developed a scoring system for early grading of polytrauma patients. METHODS: A population based trauma registry was used. INCLUSION CRITERIA: age >16 years, Abbreviated Injury Score (AIS) of the abdomen or chest >= 3 points and treatment in an intensive care unit, or Injury Severity Score (ISS) >= 16 points. The primary endpoint was hospital mortality. Patients were graded according their risk of death: low risk of death (5-14% mortality), intermediate risk patients (15-39% mortality) and high risk (>40%). Routine clinical and laboratory parameters on admission were assessed to determine their specific relevance to describe the risk profile of the patient. Based on these data, a scoring system for the description of the clinical status was developed. Statistical analysis included uniand multivariate analysis. RESULTS: 11.436 patients were included, the mean ISS was 22.7 +/- 11.2 points, 73% were male, and 95.6% had blunt injuries. The most sensitive parameters were found to be the following ones: systolic blood pressure, INR, thrombocytes, base deficit, NISS, packed red blood cells administered. The multivariate analysis revealed the following threshold levels: BP 76-90 mmHg: r = 0.249, OR 1.283: Base deficit 8-10 r = 0.474, OR 1.606; INR 1.4-2 r = 0.160, OR 1.174; NISS 35-39 r = 0.9, OR 2.46; pBRC 3-14: r = 0.671, OR 1.957. The following ranges of score values were found to be associated with different patient status: <6 points: stable patients; 6-11 points: borderline condition; >11 points: unstable patients. When using this score, 80.6% were stable, 14.6% in a borderline condition and 4.8% unstable. CONCLUSION: We developed a scoring system to discriminate polytrauma patients on admission that are at risk of systemic complications. Systolic blood pressure, INR, thrombocytes, base deficit, NISS, packed red blood cells administered are able to provide a prognosis of patients at risk of posttraumatic complications. Further prospective studies should be performed to verify this new scoring system. PMID- 26542872 TI - Femoral offset following trochanteric femoral fractures: a prospective observational study. AB - BACKGROUND: Reconstruction of the femoral offset reportedly improves outcome following total hip arthroplasty, but little is known of its influence following hip fractures. We aimed to establish the effect of the femoral offset on the medium-term functional outcome in elderly patients who had sustained trochanteric fractures requiring proximal femoral nailing. PATIENTS AND METHODS: We measured the rotation corrected femoral offset (FORC) and relative femoral offset (FORL) on plain anteroposterior radiographs of the hip in 188 patients (58 male, 130 female) with a trochanteric fracture who underwent proximal femoral nailing at our institution. The primary outcome measure was the Harris hip score (HSS) 6 and 12 months postoperatively; the Barthel index was assessed as a secondary outcome. RESULTS: The mean FORC after surgery was 58 mm (+/-11 mm), while the mean FORL was 1.21 (+/-0.22). At final follow up, we found significant inverse relationships (Spearman's rank correlation coefficient, rho) between FORC and FORL and the functional outcome assessed by the HSS (FORC: rho = -0.207, p = 0.036; FORL: rho = -0.247, p = 0.012), and FORL and the Barthel index (FORC: rho = -147, p = 0.129; FORL: rho = -0.192, p = 0.046). A consistent trend was observed after adjustment for confounding variables. CONCLUSIONS: Our results underline the biomechanical importance of the femoral offset for medium-term outcomes in elderly patients with trochanteric fractures. In contrast with the published findings on total hip arthroplasty, we found an inverse correlation between functional outcome and the extent of the reconstructed femoral offset. LEVEL OF EVIDENCE: Level I - Prognostic study. PMID- 26542874 TI - Treatment of distal intraarticular tibial fractures: A biomechanical evaluation of intramedullary nailing vs. angle-stable plate osteosynthesis. AB - In factures of the distal tibia with simple articular extension, the optimal surgical treatment remains debatable. In clinical practice, minimally invasive plate osteosynthesis and intramedullary nailing are both routinely performed. Comparative biomechanical studies of different types of osteosynthesis of intraarticular distal tibial fractures are missing due to the lack of an established model. The goal of this study was first to establish a biomechanical model and second to investigate, which are the biomechanical advantages of angle stable plate osteosynthesis and intramedullary nailing of distal intraarticular tibial fractures. Seven 4(th) generation biomechanical composite tibiae featuring an AO 43-C2 type fracture were implanted with either osteosynthesis technique. After primary lag screw fixation, 4-hole Medial Distal Tibial Plate (MDTP) with triple proximal and quadruple distal screws or intramedullary nailing with double proximal and triple 4.0mm distal interlocking were implanted. The stiffness of the implant-bone constructs and interfragmentary movement were measured under non destructive axial compression (350 and 600 N) and torsion (1.5 and 3Nm). Destructive axial compression testing was conducted with a maximal load of up to 1,200 N. No overall superior biomechanical results can be proclaimed for either implant type. Intramedullary nailing displays statistically superior results for axial loading in comparison to the MDTP. Torsional loading resulted in non statistically significant differences for the two-implant types with higher stability in the MDTP group. From a biomechanical view, the load sharing intramedullary nail might be more forgiving and allow for earlier weight bearing in patients with limited compliance. PMID- 26542875 TI - Inhaled budesonide in bronchopulmonary dysplasia. PMID- 26542876 TI - AstraZeneca halts two lung cancer drug trials. PMID- 26542877 TI - Respiratory transition in the newborn: a three-phase process. AB - We propose that the respiratory transition at birth passes through three distinct, but overlapping phases, which reflect different physiological states of the lung. Accordingly, respiratory support given to infants should be optimised to suit the underlying physiological state of the lung as it passes through each phase. During the first phase, the airways are liquid-filled and so no pulmonary gas exchange can occur. Respiratory support should, therefore, be focused on clearing the gas exchange regions of liquid. In the absence of gas exchange, little or no CO2will accumulate within the airways and, therefore, interrupting inflation pressures to allow the lung to deflate and exhale CO2is unnecessary. This is the primary rationale for administering a sustained inflation at birth. During the second phase, the gas exchange regions are mostly cleared of liquid, allowing pulmonary gas exchange to commence. However, the liquid cleared from the airways resides within the tissue during this phase, which increases perialveolar interstitial tissue pressures and the risk of liquid re-entry back into the airways. As a result, respiratory support should be optimised to minimise alveolar re-flooding during expiration, which can be achieved by applying an end expiratory pressure. The third and final phase occurs when the liquid is eventually cleared from lung tissue. Although gas exchange may be restricted by lung immaturity, injury and inflammation during this phase, considerations of how fetal lung liquid can adversely affect lung function are no longer relevant. PMID- 26542878 TI - End of life decisions for newborns: an ethical and compassionate process? PMID- 26542879 TI - Pharmacogenomics of preterm birth prevention and treatment. AB - Pharmacogenomics and personalised medicine incorporate genetic factors, historical data, and environmental exposures to predict individual variation in response to medications. The study of pharmacology and pharmacogenomics is challenging in obstetrics, and our knowledge in this area lags behind other disciplines of medicine. Some preliminary data, however, suggest that some of the interindividual variation seen in response to medications given for the prevention (progesterone) and the treatment (nifedipine, terbutaline, and others) of preterm labour may be caused by pharmacogenomic effects. A comprehensive approach, integrating clinical data, environmental factors, including concomitant medications and genotype, to optimise the prevention and treatment strategies for preterm birth, is urgently needed. TWEETABLE ABSTRACT: Some of the variation to meds for prematurity prevention/treatment may arise from pharmacogenomic effects. PMID- 26542880 TI - The mediating role of cardiovascular risk factors in the relationship between symptoms of apathy and incident cardiovascular disease in community-dwelling older individuals. AB - BACKGROUND: In old age, both apathy and depression have been associated with an increased cardiovascular disease (CVD) risk. This study evaluated the mediating role of cardiovascular risk factors in the relationship of apathy and mood symptoms with incident CVD. METHODS: Prospective cohort study of 1,790 community dwelling older individuals (70-78 years) without a history of CVD or stroke. At baseline, apathy and mood symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), of which three items represent apathy symptoms. The mediational risk factors included were diabetes mellitus (DM), body mass index (BMI), current smoking, physical inactivity, systolic blood pressure, and total cholesterol. Incident CVD was evaluated after two years of follow-up. Data were analyzed using structural equation modeling (SEM). RESULTS: Incident CVD occurred in 59 (3.3%) participants. Apathy symptoms had a significant estimated total effect on incident CVD, with increases of 2.2% for each unit increase in apathy score. Of this total effect, 22.7% was due to the mediational effects of physical inactivity (13.6%), current smoking (4.5%), and DM (4.5%). The remaining 77.3% was due to direct effects reflecting other mediational dynamics. No significant (in)direct effects of mood symptoms on incident CVD were found. CONCLUSIONS: Physical inactivity, smoking, and DM account for nearly one-fourth of the variation reflecting the link between apathy symptoms and incident CVD. This illustrates the relevance of unfavorable health behaviors and assessment of DM in older individuals with apathy. The majority of the effect of apathy symptoms on incident CVD is caused by other, yet unknown, factors. PMID- 26542882 TI - Extreme Sensitivity of Room-Temperature Photoelectric Effect for Terahertz Detection. AB - Extreme sensitivity of room-temperature photoelectric effect for terahertz (THz) detection is demonstrated by generating extra carriers in an electromagnetic induced well located at the semiconductor, using a wrapped metal-semiconductor metal configuration. The excellent performance achieved with THz detectors shows great potential to open avenues for THz detection. PMID- 26542881 TI - Highly efficient radiosensitization of human glioblastoma and lung cancer cells by a G-quadruplex DNA binding compound. AB - Telomeres are nucleoprotein structures at the end of chromosomes which stabilize and protect them from nucleotidic degradation and end-to-end fusions. The G-rich telomeric single-stranded DNA overhang can adopt a four-stranded G-quadruplex DNA structure (G4). Stabilization of the G4 structure by binding of small molecule ligands enhances radiosensitivity of tumor cells, and this combined treatment represents a novel anticancer approach. We studied the effect of the platinum derived G4-ligand, Pt-ctpy, in association with radiation on human glioblastoma (SF763 and SF767) and non-small cell lung cancer (A549 and H1299) cells in vitro and in vivo. Treatments with submicromolar concentrations of Pt-ctpy inhibited tumor proliferation in vitro with cell cycle alterations and induction of apoptosis. Non-toxic concentrations of the ligand were then combined with ionizing radiation. Pt-ctpy radiosensitized all cell lines with dose-enhancement factors between 1.32 and 1.77. The combined treatment led to increased DNA breaks. Furthermore, a significant radiosensitizing effect of Pt-ctpy in mice xenografted with glioblastoma SF763 cells was shown by delayed tumor growth and improved survival. Pt-ctpy can act in synergy with radiation for efficient killing of cancer cells at concentrations at which it has no obvious toxicity per se, opening perspectives for future therapeutic applications. PMID- 26542883 TI - Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells. AB - Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. PMID- 26542884 TI - Exciton and Trion Dynamics in Bilayer MoS2. AB - The control of exciton and triondynamics in bilayer MoS2 is demonstrated, via the comodulations by both temperature and electric field. The calculations here show that the band structure of bilayer MoS2 changes from indirect at room temperature toward direct nature as temperature decreases, which enables the electrical tunability of the K-K direct PL transition in bilayer MoS2 at low temperature. PMID- 26542885 TI - Metals and neurodegeneration. PMID- 26542886 TI - Vascular Endothelial Growth Factor A Regulates the Secretion of Different Angiogenic Factors in Lung Cancer Cells. AB - Vascular endothelial growth factor A (VEGFA) is one of the main mediators of angiogenesis in non-small cell lung cancer (NSCLC). Recently, it has been described an autocrine feed-forward loop in NSCLC cells in which tumor-derived VEGFA promoted the secretion of VEGFA itself, amplifying the proangiogenic signal. In order to investigate the role of VEGFA in lung cancer progression, we assessed the effects of recombinant VEGFA on proliferation, migration, and secretion of other angiogenic factors in A549, H1975, and HCC827 NSCLC cell lines. We found that VEGFA did not affect NSCLC cell proliferation and migration. On the other hand, we demonstrated that VEGFA not only produced a strong and persistent increase of VEGFA itself but also significantly induced the secretion of a variety of angiogenic factors, including follistatin (FST), hepatocyte growth factor (HGF), angiopoietin-2 (ANGPT2), granulocyte-colony stimulating factor (G-CSF), interleukin (IL)-8, leptin (LEP), platelet/endothelial cell adhesion molecule 1 (PECAM-1), and platelet-derived growth factor bb (PDGF-BB). PI3K/AKT, RAS/ERK, and STAT3 signalling pathways were found to mediate the effects of VEGFA in NSCLC cell lines. We also observed that VEGFA regulation mainly occurred at post-transcriptional level and that NSCLC cells expressed different isoforms of VEGFA. Collectively, our data suggested that VEGFA contributes to lung cancer progression by inducing a network of angiogenic factors, which might offer potential for therapeutic intervention. PMID- 26542887 TI - Intravenous Administration of Simvastatin Improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats. AB - Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. The beneficial effects of oral simvastatin have been reported in pre-clinical models of traumatic brain injury (TBI). The current study was designed to evaluate the potential beneficial effects of simvastatin in a model of severe penetrating TBI using an intravenous (IV) route of administration. Rats were subjected to unilateral frontal penetrating ballistic-like brain injury (PBBI), and simvastatin was delivered intravenously at 30 min and 6 h post-injury and continued once daily for either 4 or 10 days post-PBBI. Motor function was assessed on the rotarod and cognitive performance was evaluated using the Morris water maze (MWM) task. Serum levels of inflammatory cytokines and the astrocytic biomarker, glial fibrillary acidic protein (GFAP), were quantified at 1 h, 4 h, and 24 h post-injury. Histopathological damage was assessed at the terminal end-point. Rotarod testing revealed significant motor deficits in all injury groups but no significant simvastatin-induced therapeutic benefits. All PBBI-injured animals showed cognitive impairment on the MWM test; however, 10-day simvastatin treatment mitigated these effects. Animals showed significantly improved latency to platform and retention scores, whereas the 4-day treatment regimen failed to produce any significant improvements. Biomarker and cytokine analysis showed that IV simvastatin significantly reduced GFAP, interleukin (IL)-1alpha, and IL-17 serum levels by 4.0-, 2.6-, and 7.0-fold, respectively, at 4 h post-injury. Collectively, our results demonstrate that IV simvastatin provides significant protection against injury-induced cognitive dysfunction and reduces TBI-specific biomarker levels. Further research is warranted to identify the optimal dose and therapeutic window for IV delivery of simvastatin in models of severe TBI. PMID- 26542888 TI - Quantitative sensory testing of dentinal sensitivity in healthy humans. AB - OBJECTIVE: The study was to provide information on quantitative sensory testing (QST) of normal teeth to establish a sensory profile and investigate the possible gender and regional differences. MATERIALS AND METHODS: A modified QST protocol was applied on both left and right upper-jaw incisors and pre-molar sof 14 healthy men and 14 age-matched healthy women (18-25 years). Mechanical stimulus sensitivity (MSS), cold detection threshold (CDT), cold pain threshold (CPT), warm detection threshold (WDT), heat pain threshold (HPT), electrical detection threshold (EDT) and electrical pain threshold (EPT) were determined from the four teeth (labial side of incisor and buccal side of the first premolar). The QST parameters were analysed by ANOVA. RESULTS: The applied mechanical or thermal stimuli did not evoke any pain sensation. A normal tooth did not seem to be able to distinguish between the warm or cold stimuli applied. No significant differences were found between genders (p > 0.099) or teeth (p > 0.053) regarding mechanical and thermal stimuli. The EDT and EPT were significantly higher in the pre-molar compared with incisor (p < 0.002) without gender differences (p > 0.573). CONCLUSION: The established methods and results provided important information on diagnosis and treatment evaluation of dentinal hypersensitivity. PMID- 26542890 TI - Intriguing Electrostatic Potential of CO: Negative Bond-ends and Positive Bond cylindrical-surface. AB - The strong electronegativity of O dictates that the ground state of singlet CO has positively charged C and negatively charged O, in agreement with ab initio charge analysis, but in disagreement with the dipole direction. Though this unusual phenomenon has been fairly studied, the study of electrostatic potential (EP) for noncovalent interactions of CO is essential for better understanding. Here we illustrate that both C and O atom-ends show negative EP (where the C end gives more negative EP), favoring positively charged species, whereas the cylindrical surface of the CO bond shows positive EP, favoring negatively charged ones. This is demonstrated from the interactions of CO with Na(+), Cl(-), H2O, CO and benzene. It can be explained by the quadrupole driven electrostatic nature of CO (like N2) with very weak dipole moment. The EP is properly described by the tripole model taking into account the electrostatic multipole moments, which has a large negative charge at a certain distance protruded from C, a large positive charge on C, and a small negative charge on O. We also discuss the EP of the first excited triplet CO. PMID- 26542889 TI - Comparison of health-related quality of life between patients with stage 3 and 4 chronic kidney disease and patients undergoing continuous ambulatory peritoneal dialysis. AB - AIM: This study compared health-related quality of life in patients with early to mid-stage chronic kidney disease. METHODS: This study utilized a comparative descriptive design. Patients receiving continuous ambulatory peritoneal dialysis were recruited from a hospital in Korea. Information from patients with stage 3 and 4 chronic kidney disease was obtained from Korean national survey data. A total of 75 pairs were matched using the propensity score method. Health-related quality of life was compared using the European Quality of Life-5 Dimensions questionnaire. RESULTS: Only 4% of patients with stage 3 or 4 chronic kidney disease are aware of their disease. These patients have decreased mobility and ability to perform their usual activities (chi(2) = 10.77, P = 0.001; chi(2) = 7.22, P = 0.007, respectively). However, they have lower levels of anxiety and depression than patients undergoing continuous ambulatory peritoneal dialysis (chi(2) = 13.37, P < 0.001). The European Quality of Life-5 Dimensions utility scores do not differ between the two patient groups. CONCLUSION: The results of this study suggest that more effective management programs are needed to improve health-related quality of life in patients at all stages of chronic kidney disease. Educational intervention in asymptomatic patients is important to increase awareness and early detection of chronic kidney disease. PMID- 26542891 TI - Challenges in carrier-mediated intracellular delivery: moving beyond endosomal barriers. AB - The deployment of molecular to microscale carriers for intracellular delivery has tremendous potential for biology and medicine, especially for in vivo therapies. The field remains limited, however, by a poor understanding of how carriers gain access to the cell interior. In this review, we provide an overview of the different types of carriers, their speculated modes of entry, putative pathways of vesicular transport, and sites of endosomal escape. We compare this alongside pertinent examples from the cell biology of how viruses, bacteria, and their effectors enter cells and escape endosomal confinement. We anticipate insights into the mechanisms of cellular entry and endosomal escape will benefit future research efforts on effective carrier-mediated intracellular delivery. WIREs Nanomed Nanobiotechnol 2016, 8:465-478. doi: 10.1002/wnan.1377 For further resources related to this article, please visit the WIREs website. PMID- 26542892 TI - Nuclear receptor ecdysone-induced protein 75 is required for larval-pupal metamorphosis in the Colorado potato beetle Leptinotarsa decemlineata (Say). AB - 20-hydroxyecdysone (20E) and juvenile hormone (JH) are key regulators of insect development. In this study, three Leptinotarsa decemlineata Ecdysone-induced protein 75 (LdE75) cDNAs (LdE75A, B and C) were cloned from L. decemlineata. The three LdE75 isoforms were highly expressed just before or right after each moult. Within the fourth larval instar, they showed a small rise and a big peak 40 and 80 h after ecdysis. The expression peaks of the three LdE75s coincided with the peaks of circulating 20E levels. In vitro midgut culture and in vivo bioassay revealed that 20E and an ecdysteroid agonist halofenozide (Hal) enhanced LdE75 expression in the day 1 final larval instars. Conversely, a decrease in 20E by feeding a double-stranded RNA (dsRNA) against an ecdysteroidogenesis gene, Shade (LdSHD), repressed the expression of LdE75. Moreover, Hal upregulated the expression of the three LdE75s in LdSHD-silenced larvae. Thus, 20E pulses activate the transcription of LdE75s. Furthermore, ingesting dsE75-1 and dsE75-2 from a common fragment of the three isoforms successfully knocked down these LdE75s, and caused developmental arrest. Finally, knocking down LdE75s significantly repressed the transcription of three ecdysteroidogenesis genes, lowered the 20E titre and affected the expression of two 20E-response genes. Silencing LdE75s also induced the expression of a JH biosynthesis gene, increased JH titre and activated the transcription of a JH early-inducible gene. Thus, Ld E75s are required for larval-pupal metamorphosis and act mainly by modulating 20E and JH titres and mediating their signalling pathways. PMID- 26542894 TI - What would make a dietary intake adequate in individuals with spinal cord injury. PMID- 26542893 TI - ETV6-LPXN fusion transcript generated by t(11;12)(q12.1;p13) in a patient with relapsing acute myeloid leukemia with NUP98-HOXA9. AB - ETV6, which encodes an ETS family transcription factor, is frequently rearranged in human leukemias. We show here that a patient with acute myeloid leukemia with t(7;11)(p15;p15) gained, at the time of relapse, t(11;12)(q12.1;p13) with a split ETV6 FISH signal. Using 3'-RACE PCR analysis, we found that ETV6 was fused to LPXN at 11q12.1, which encodes leupaxin. ETV6-LPXN, an in-frame fusion between exon 4 of ETV6 and exon 2 of LPXN, did not transform the interleukin-3-dependent 32D myeloid cell line to cytokine independence; however, an enhanced proliferative response was observed when these cells were treated with G-CSF without inhibition of granulocytic differentiation. The 32D and human leukemia cell lines each transduced with ETV6-LPXN showed enhanced migration towards the chemokine CXCL12. We show here for the first time that LPXN is a fusion partner of ETV6 and present evidence indicating that ETV6-LPXN plays a crucial role in leukemia progression through enhancing the response to G-CSF and CXCL12. PMID- 26542895 TI - Monitoring Agitated Behavior After acquired Brain Injury: Onset, Duration, Intensity, and Nursing Shift Variation. AB - PURPOSE: To describe the onset, duration, intensity, and nursing shift variation of agitated behavior in patients with acquired brain injury (ABI) at a rehabilitation hospital. DESIGN: Prospective descriptive study. METHODS: A total of 11 patients with agitated behavior were included. Agitated behavior was registered with the Agitated Behavior Scale (ABS). The nurse or therapist allocated the individual patient assessed ABS during each shift. Intensity of agitated behavior was tested using exact test. A within-subject shift effect was analyzed with repeated-measure ANOVA. FINDINGS: The onset of agitated behavior was at a median of 14 (1-28) days from admission. Seven patients remained agitated beyond 3 weeks from onset. Severe intensity of agitation was observed in 86 of 453 nursing shifts. Differences in agitated behavior between day, evening, and night shifts were found, F(2.20) = 7.90, p = .008, with tendencies of increased agitated behavior in day and evening shifts compared to night shifts. CONCLUSION: Agitated behavior had a late onset, was severe, and long-lasting in the present sample of patients. CLINICAL RELEVANCE: The study increases awareness on the potential challenge of agitated behavior in patients with ABI. PMID- 26542896 TI - Automated Outreach for Cardiovascular-Related Medication Refill Reminders. AB - The objective of this study was to evaluate the effectiveness of an automated telephone system reminding patients with hypertension and/or cardiovascular disease to obtain overdue medication refills. The authors compared the intervention with usual care among patients with an overdue prescription for a statin or lisinopril-hydrochlorothiazide (lisinopril-HCTZ). The primary outcome was refill rate at 2 weeks. Secondary outcomes included time to refill and change in low-density lipoprotein cholesterol and blood pressure. Significantly more patients who received a reminder call refilled their prescription compared with the usual-care group (statin cohort: 30.3% vs 24.9% [P<.0001]; lisinopril-HCTZ cohort: 30.7% vs 24.2% [P<.0001]). The median time to refill was shorter in patients receiving the reminder call (statin cohort: 29 vs 36 days [P<.0001]; lisinopril-HCTZ cohort: 24 vs 31 days [P<.0001]). There were no statistically significant differences in mean low-density lipoprotein cholesterol and blood pressure. These findings suggest the need for interventions that have a longer term impact. PMID- 26542897 TI - Strengthening behavior of carbon/metal nanocomposites. AB - Nanocomposites reinforced with nano-scale reinforcements exhibit excellent mechanical properties with low volume fraction of the reinforcement. For instance, only an addition of 0.7 vol.% few-layer graphene (FLG) into the pure titanium shows strength of ~1.5 GPa, obviously much superior to that of the monolithic titanium. The strengthening efficiency of composites is determined by several factors such as reinforcement geometrical/spatial characteristics and interfacial features between the matrix and the reinforcement. For the metal matrix nanocomposites (MMNCs), since the nano-scale reinforcement has significantly high specific surface area, interfacial feature is more important and has to be clearly evaluated in understanding property of MMNCs. Although many researchers suggested the theoretical work using continuum mechanics in order to estimate the mechanical properties of the metallic composites, a clear determination has yet not to be proven by systematic experimental works. Here, we provide a new model to predict strength and stiffness of MMNCs based on quantitative analysis of efficiency parameters in which interface feature is strongly emphasized. To validate the model, we select multi-walled carbon nanotube (MWCNT) and FLG for reinforcement, and titanium (Ti) and aluminum (Al) for the matrix to modify bonding strength and specific surface area in the MMNCs. PMID- 26542898 TI - Compassion is a constant. AB - Compassion is a powerful word that describes an intense feeling of commiseration and a desire to help those struck by misfortune. Most people know intuitively how and when to offer compassion to relieve another person's suffering. In health care, compassion is a constant; it cannot be rationed because emergency nurses have limited time or resources to manage increasing demands. PMID- 26542899 TI - Patients in Northern Ireland can see waiting times online. AB - Waiting time details for emergency departments in Northern Ireland can now be accessed online. PMID- 26542900 TI - Call for better advice on concussion in sports. AB - Failure to manage the risk of concussion properly could lead to fewer people playing sport, according to Scotland's chief medical officer, writing in the British Journal of Sports Medicine. PMID- 26542901 TI - Without more nurses, NHS 111 staff could be 'overwhelmed'. AB - Urgent action is needed to tackle the nurse staffing shortages at the NHS 24-hour non-emergency helpline and stop the service being 'overwhelmed' this winter, according to the RCN. PMID- 26542904 TI - Rise in emergency admissions linked with mental health. AB - People with mental health problems are five times more likely to be admitted to hospital in an emergency than the rest of the population, a survey has revealed. PMID- 26542905 TI - Professionals offer their opinions about the forthcoming nursing and midwifery strategy. AB - Over the next few weeks, chief nursing officer for England Jane Cummings and her team will draw up the first draft of a new nursing and midwifery strategy. The draft strategy is set to be presented to around 500 senior nurses attending the chief nurse's annual two-day summit in Birmingham, to be held next month and entitled Leading Change and Creating Value. PMID- 26542906 TI - Extra funds set to relieve pressure on staff this winter. AB - The NHS could not be better prepared for winter. At least that was the message when the Department of Health, NHS England and Public Health England launched their Stay Well This Winter campaign. PMID- 26542907 TI - Epilepsy passports issued to convey crucial information in emergencies. AB - A new epilepsy passport has been created for about 60,000 children in the UK who have the the condition. PMID- 26542908 TI - Stroke patients set to receive new treatment. AB - A new technique to remove blood clots from arteries could soon be integrated into everyday practice to treat patients with ischaemic stroke. PMID- 26542914 TI - Board's eye view - Role of the scribe. AB - Good and clear documentation of events in an emergency situation is paramount; as the adage goes, 'if it is not written in the notes it never happened'. The role of the scribe in these situations is a complex one and that individual is invaluable to the team. PMID- 26542915 TI - How to be a 'newbie'. AB - Nursing careers spent solely in one area or department have become a thing of the past. Nurses are constantly moving abroad, to different specialties or up the ranks. In each case they will become new team members, or 'newbies'. PMID- 26542916 TI - Preparing for disaster. AB - Natural disasters and armed conflicts affect the health of hundreds of millions of people around the world, not only directly through violence and trauma, but also through damage to social and economic infrastructures. Disaster preparedness, however, can help ensure that health systems and communities are better prepared to cope with emergencies. PMID- 26542922 TI - Role of partnership in a 24/7 stroke research project. AB - The Royal Stoke has become the first hospital in the country to provide round-the clock research cover for hyperacute stroke and trauma trials involving patients presenting for emergency care services. The biggest challenge has been the small window of opportunity to recruit patients to a stroke trial before results are lost to the speed and impact of the condition. Good working relationships between research nurses and emergency care teams have proved pivotal in creating the fully funded 24/7 cover. PMID- 26542923 TI - Reversal sign: a red-flag in emergency departments. AB - The reversal sign is an ominous finding seen on computed tomographic images of the brain as an inversion of the normal attenuation relationship between grey and white matter. This article describes the pathophysiology of the reversal sign, which indicates irreversible neural tissue damage, and includes a brief case study of a child who drowned and later developed this sign. The child died two hours after presenting to the emergency department. Emergency healthcare professionals should be aware of this sign, which is significant in terms of diagnosis, management and prognosis. Knowledge of the reversal sign will also help emergency nurses support relatives who are about to be notified about the possible long-term neurological deficits in, or death of, their loved one. PMID- 26542924 TI - Researching participant recruitment times. AB - Conducting research in emergency departments is relatively new, and there are a number of ethical and practical challenges to recruiting patients in these settings. In 2008, the Emergency Medicine Research Group Edinburgh (EMERGE) was set up at the Royal Infirmary of Edinburgh emergency department to support researchers and encourage the growth of research in emergency medicine. As part of a review of their working methods, the group's clinical nurse researchers undertook a small study to identify participant recruitment times. The results showed a significant difference between perceived and actual recruitment times, which has implications for planning staff numbers and budgets. This article describes the evaluation process and methods of data collection, and discusses the results. PMID- 26542925 TI - Assessing and managing spider and scorpion envenomation. AB - Envenomation by spiders or scorpions is a public health problem in many parts of the world and is not isolated to the tropics and subtropics. Spiders and scorpions can be unintentionally transported globally, and keeping them as pets is becoming more popular, so envenomation can occur anywhere. Emergency nurses should be prepared to assess and treat patients who present with a bite or sting. This article gives an overview of the signs, symptoms and treatment of envenomation by species of arachnids that are clinically significant to humans. PMID- 26542926 TI - Structure of a Kunitz-type potato cathepsin D inhibitor. AB - Potato cathepsin D inhibitor (PDI) is a glycoprotein of 188 amino acids which can inhibit both the aspartic protease cathepsin D and the serine protease trypsin. Here we report the first X-ray structure of PDI at a resolution of 2.1 A showing that PDI adopts a beta-trefoil fold, which is typical of the Kunitz-family protease inhibitors, with the inhibitory loops protruding from the core. Possible reactive-site loops including one involving a unique disulphide and another involving a protruding 310 helix are identified and docking studies indicate the mode of action of this unusual bi-functional inhibitor. PMID- 26542927 TI - Culture and religious beliefs in relation to reproductive health. AB - An increasing number of contemporary research publications acknowledge the influence of religion and culture on sexual and reproductive behavior and health care utilization. It is currently hypothesized that religious influences can partly explain disparities in sexual and reproductive health outcomes. In this paper, we will pay particular attention to Muslims in sexual and reproductive health care. This review reveals that knowledge about devout Muslims' own experience of sexual and reproductive health-care matters is limited, thus providing weak evidence for modeling of efficient practical guidelines for sexual and reproductive health care directed at Muslim patients. Successful outcomes in sexual and reproductive health of Muslims require both researchers and practitioners to acknowledge religious heterogeneity and variability, and individuals' possibilities to negotiate Islamic edicts. Failure to do so could lead to inadequate health-care provision and, in the worst case, to suboptimal encounters between migrants with Muslim background and the health-care providers in the receiving country. PMID- 26542928 TI - Malignancies in pregnancy. AB - Malignancy complicating pregnancy is fortunately rare, affecting one in 1000 to one in 1500 pregnancies. Optimal treatment involves balancing the benefit of treatment for the mother while minimizing harm to the fetus. This balance is dependent on the extent of the disease, the recommended course of treatment, and the gestational age at which treatment is considered. Both surgery and chemotherapy are generally safe in pregnancy, whereas radiation therapy is relatively contraindicated. Iatrogenic prematurity is the most common pregnancy complication, as infants are often delivered for maternal benefit. In general, however, survival does not differ from the nonpregnant population. These patients require a multidisciplinary approach for management with providers having experience in caring for these complex patients. The aim of this review was to provide an overview for obstetricians of the diagnosis and management of malignancy in pregnancy. PMID- 26542929 TI - Stem cells from amniotic fluid--Potential for regenerative medicine. AB - Regenerative medicine has recently been established as an emerging field focussing on repair, replacement or regeneration of cells, tissues and whole organs. The significant recent advances in the field have intensified the search for novel sources of stem cells with potential for therapy. Recently, researchers have identified the amniotic fluid as an untapped source of stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. Stem cells from the amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, which make them an ideal candidate for tissue engineering applications. In addition, their ability to engraft in injured organs and modulate immune and repair responses of host tissues suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases affecting major tissues/organs. This review summarises the evidence on amniotic fluid cells over the past 15 years and explores the potential therapeutic applications of amniotic fluid stem cells and amniotic fluid mesenchymal stem cells. PMID- 26542930 TI - Uterine myomata: Organ-preserving surgery. AB - Most women with uterine myoma are asymptomatic and do not require any treatment. However, myoma can also lead to menorrhagia, pressure symptoms, abdominal pain, and infertility. Management of symptomatic women with myoma depends on several factors, including age, desire for fertility, and myoma characteristics. Uterine myoma that distorts the uterine cavity, either submucous myoma or intramural myoma, with a submucous component reduces fertility, and is associated with increased uterine bleeding. The treatment of choice is hysteroscopic myomectomy or abdominal myomectomy, preferably by laparoscopy. Robotic assistance in laparoscopic myomectomy leads to outcomes similar to conventional laparoscopic myomectomy. However, it is expensive. Newer techniques include either laparoscopic or transcervical radiofrequency thermal ablation. PMID- 26542931 TI - Pulmonary Artery Reconstruction with Donor Aortic Homograft During Cardiac Transplantation in the Failed Fontan Circulation. AB - The advanced surgical management of patients with single ventricle physiology, in particular the hypoplastic left heart syndrome, has resulted in an increased number of patients with a Fontan circulation. In a proportion of these patients, the Fontan circulation will ultimately fail and cardiac transplantation may be required. Their course may be complicated by the hemodynamic consequences of the failing Fontan, multiple previous operations, and the frequent need for complex reconstruction at transplantation. We describe a patient with a failed modified Fontan circulation requiring concomitant pulmonary artery reconstruction and cardiac transplantation and review potential reconstruction techniques. PMID- 26542932 TI - SDS-assisted solvothermal synthesis of rose-like BiOBr partially enclosed by {111} facets and enhanced visible-light photocatalytic activity. AB - Rose-like BiOBr nanostructures with exposed {111} facets were firstly synthesized with the assistance of an anionic surfactant, sodium dodecyl sulfate (SDS), via a facile solvothermal route. The 2D nanosheets, which self-assembled to form the 3D structures, were achieved with the thickness decreasing from average 120 nm to 20 nm. Specially, the nanosheets were partially enclosed by {111} facets due to the effect of SDS. The as-prepared BiOBr with {111} facets exhibited excellent electrochemical behavior and photocatalytic activity under both visible light (lambda>= 420 nm) and monochromatic light (lambda = 420 nm) irradiation. PMID- 26542933 TI - PCNA and apoptosis during post-spawning ovarian remodeling in the teleost Oreochromis niloticus. AB - The balance between cell proliferation and apoptosis is crucial for tissue development and homeostasis. The present study investigated the contribution of proliferating cell nuclear antigen (PCNA) and apoptosis during ovarian remodeling after spawning in the Nile tilapia Oreochromis niloticus. Breeding females were kept in controlled conditions and ovary samples were collected weekly for TUNEL assay, immunohistochemistry for PCNA and caspase-3 and morphometric analysis. During the follicular growth, PCNA labeled mainly the nuclei of oocytes and follicular cells in a high proportion of follicles especially in primary growth, while a low occurrence of apoptosis in follicular and theca cells was detected. At 0-3 days post-spawning, post-ovulatory follicles showed no proliferative activity, however the follicular cells exhibited high rates of apoptosis. At 7-10 days, PCNA labeled the thecal cells in a low proportion of post-ovulatory follicles, which showed follicular cells with lower rates of apoptosis. PCNA labeled mainly the theca in the advanced and late stages of atretic follicles, while the follicular cells exhibited a significant increase of apoptosis along follicular atresia. We concluded that PCNA and apoptosis work cooperatively to ensuring the success of follicle development and maintaining of tissue homeostasis during follicular growth. PCNA and apoptosis are also essential mechanisms in the follicular regression during post-spawning ovarian recovery in the Nile tilapia. PMID- 26542935 TI - No evidence of 1918 influenza pandemic origin in Chinese laborers/soldiers in France. AB - Laborers and soldiers from China and Southeast Asia recruited during the First World War by Britain and France have been suggested as the origin of the 1918 influenza pandemic in Western Europe. This study aimed to review the available data to better understand the sources and origins of the 1918 influenza pandemic, and clarify whether, in fact, there was an Asian connection to its onset. We reviewed official mortality lists from the Commonwealth War Graves Commission and the French Ministry of Defence for all-cause (Britain) and pneumonia/influenza (France) mortality, respectively. The results indicated that influenza mortality (estimated 1/1000) in Chinese and Southeast Asian laborers and soldiers lagged other co-located military units by several weeks. This finding does not support a Southeast Asian importation of lethal influenza to Europe in 1918. PMID- 26542936 TI - A multi-faceted knowledge translation approach to support persons with stroke and cognitive impairment: evaluation protocol. AB - BACKGROUND: Patients with cognitive impairments following a stroke are often denied access to inpatient rehabilitation. The few patients with cognitive impairment admitted to rehabilitation generally receive services based on outdated impairment-reduction models, rather than recommended function-based approaches. Both reduced access to rehabilitation and the knowledge-to-practice gap stem from a reported lack of skills and knowledge regarding cognitive rehabilitation on the part of inpatient rehabilitation team members. To address these issues, a multi-faceted knowledge translation (KT) initiative will be implemented and evaluated. It will be targeted specifically at the inter professional application of the cognitive orientation to daily occupational performance (CO-OP). CO-OP training combined with KT support is called CO-OP KT. The long-term objective of CO-OP KT is to optimize functional outcomes for individuals with stroke and cognitive impairments. Three research questions are posed: 1. Is the implementation of CO-OP KT associated with a change in the proportion of patients with cognitive impairment following a stroke accepted to inpatient rehabilitation? 2. Is the implementation of CO-OP KT associated with a change in rehabilitation clinicians' practice, knowledge, and self-efficacy related to implementing the CO-OP approach, immediately following and 1 year later? 3. Is CO-OP KT associated with changes in activity, participation, and self-efficacy to perform daily activities in patients with cognitive impairment following stroke at discharge from inpatient rehabilitation and at 1-, 3-, and 6 month follow-ups? METHODS/DESIGN: Three interrelated studies will be conducted. Study 1 will be a quasi-experimental, interrupted time series design measuring monthly summaries of stroke unit level data. Study 2, which relates to changes in health care professional practice and self-efficacy, will be a single group pre post evaluation design incorporating chart audits and a self-report survey. Study 3 will assess patient functional outcomes using a non-randomized design with historical controls. Assessments will occur during admission and discharge from rehabilitation and at 1, 3, and 6 months following discharge from rehabilitation. DISCUSSION: This project will advance knowledge about the degree to which the implementation of a supported KT initiative can sustainably change health system, knowledge, and patient outcomes. PMID- 26542937 TI - The physiological correlates of children's emotions in contexts of moral transgression. AB - Heightened attention to sociomoral conflicts and arousal at the prospect of committing moral transgressions are thought to increase the likelihood of negatively valenced moral emotions (NVMEs; e.g., guilt) in children. Here, we tested this biphasic model of moral emotions with a psychophysiological framework. For a series of vignettes depicting moral transgressions, 5- and 8 year-olds (N=138) were asked to anticipate their emotions as hypothetical victimizers. Their responses were coded for the presence and intensity of NVMEs. In addition, their heart rate (HR) was calculated for three intervals of interest: a baseline period, the presentation of vignettes, and the anticipation of emotions following vignettes. We used multilevel modeling to examine how change in children's HR across these intervals related to the intensity of their NVMEs. Those who experienced greater HR deceleration from baseline to vignettes and greater acceleration from vignettes to anticipated emotions reported more intense NVMEs. We discuss the potential attention- and arousal-related processes behind children's physiological reactivity and anticipated emotions in contexts of moral transgression. PMID- 26542934 TI - Timing by rhythms: Daily clocks and developmental rulers. AB - Biological rhythms are widespread, allowing organisms to temporally organize their behavior and metabolism in advantageous ways. Such proper timing of molecular and cellular events is critical to their development and health. This is best understood in the case of the circadian clock that orchestrates the daily sleep/wake cycle of organisms. Temporal rhythms can also be used for spatial organization, if information from an oscillating system can be recorded within the tissue in a manner that leaves a permanent periodic pattern. One example of this is the "segmentation clock" used by the vertebrate embryo to rhythmically and sequentially subdivide its elongating body axis. The segmentation clock moves with the elongation of the embryo, such that its period sets the segment length as the tissue grows outward. Although the study of this system is still relatively young compared to the circadian clock, outlines of molecular, cellular, and tissue-level regulatory mechanisms of timing have emerged. The question remains, however, is it truly a clock? Here we seek to introduce the segmentation clock to a wider audience of chronobiologists, focusing on the role and control of timing in the system. We compare and contrast the segmentation clock with the circadian clock, and propose that the segmentation clock is actually an oscillatory ruler, with a primary function to measure embryonic space. PMID- 26542938 TI - Biological motion perception links diverse facets of theory of mind during middle childhood. AB - Two cornerstones of social development--social perception and theory of mind- undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12 years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind. PMID- 26542939 TI - [Beckwith-Wiedemann syndrome: What do you search in prenatal diagnosis? About 14 cases]. AB - OBJECTIVES: Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth syndrome and has an incidence of 1/13,700. The majority of the cases are diagnosed after birth. Patients with BWS have an increased risk of neonatal hypoglycemia and embryonal tumors development in childhood. We wanted to identify the ultrasound signs that must alert physicians to prepare best perinatal management strategies. METHODS: We conducted a retrospective study of a population of 14 cases of BWS diagnosed in perinatal period; four of them were detected prenatally by ultrasound. The anomalies signs described in prenatal were analyzed and compared with the clinical features of the postnatal period. RESULTS: The major features reported were represented by macrosomia for 71.4% with an increase of abdominal circumference, and macroglossia for 78.6%. The minor features were various with 64% of visceromegaly (nephromegaly and/or hepatomegaly), 50% of hydramnios and for 80% of male children a genital anomaly (crytorchidism and/or hypospadias). CONCLUSION: This study identified some prenatal ultrasound signs that should alert the clinician to the possibility of BWS. A genetic conseling, after confirmation by molecular diagnosis, could be proposed in a near future in prenatal, and could improve postnatal management strategies for these affected children at high postnatal risk. PMID- 26542940 TI - Semaphorin 4A as novel regulator and promising therapeutic target in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease manifesting in joint destruction. The recognized hallmark of RA pathogenesis is the involvement of immune cells which produce many mediators potentiating an inflammatory environment. RA synovial fibroblasts (RASFs) contribute significantly to disease progression by initiating and regulating many pathways of joint destruction. Detailed molecular insights into RASF biology may lead to identification of important therapeutic targets. The discovery of common molecular targets for joint resident and inflammatory cells may help to develop the most effective therapeutic strategy. One such pathway includes semaphorin 4A as reported in a recent article in Arthritis Research & Therapy. PMID- 26542941 TI - Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma. AB - The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 +/- 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 +/- 5.2%) and somatotroph cells (94.7 +/- 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 +/- 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease. PMID- 26542943 TI - A simulation study of sperm motility hydrodynamics near fish eggs and spheres. AB - For teleost fish fertilisation, sperm must proceed through a small opening on the egg surface, referred to as the micropyle. In this paper, we have used boundary element simulations to explore whether the hydrodynamic attraction between sperm and a fish egg can be a sperm guidance cue. Hydrodynamical egg-sperm interactions alone do not increase the chances of an egg encounter, nor do they induce surface swimming for virtual turbot fish sperm across smooth spheres with a diameter of 1mm, which is representative of a turbot fish egg. When a repulsive surface force between the virtual turbot sperm and the egg is introduced, as motivated by surface charge and van-der-Waals interactions for instance, we find that extended surface swimming of the virtual sperm across a model turbot egg occurs, but ultimately the sperm escapes from the egg. This is due to the small exit angle of the scattering associated with the initial sperm-egg interaction at the egg surface, leading to a weak drift away from the egg, in combination with a weak hydrodynamical attraction between both gametes, though the latter is not sufficient to prevent eventual escape. The resulting transience is not observed experimentally but is a detailed quantitative difference between theory and observation in that stable surface swimming is predicted for eggs with radii larger than about 1.8mm. Regardless, the extended sperm swimming trajectory across the egg constitutes a two-dimensional search for the micropyle and thus the egg is consistently predicted to provide a guidance cue for sperm once they are sufficiently close. In addition, the observation that the virtual turbot sperm swims stably next to a flat plane given repulsive surface interactions, but does not swim stably adjacent to a turbot-sized egg, which is extremely large by sperm-lengthscales, also highlights that the stability of sperm swimming near a boundary is very sensitive to geometry. PMID- 26542942 TI - High-level Plasmodium falciparum sulfadoxine-pyrimethamine resistance with the concomitant occurrence of septuple haplotype in Tanzania. AB - BACKGROUND: Tanzania abandoned sulfadoxine-pyrimethamine (SP) as the first-line treatment for uncomplicated malaria in 2006 due to high levels Plasmodium falciparum resistance. However, SP is still being used for intermittent preventive treatment during pregnancy (IPTp-SP). This study aimed to assess the pattern of P. falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations and associated haplotypes in areas with different malaria transmission intensities in mainland Tanzania, 6 years after withdrawal of SP as a first-line treatment regimen for uncomplicated malaria. METHODS: A total of 264 samples were collected during cross-sectional surveys in three districts of Muheza, Muleba and Nachingwea in Tanga, Kagera and Lindi regions, respectively. Parasite genomic DNA was extracted from P. falciparum positive samples. The Pfdhfr, Pfdhps single nucleotide polymorphisms (SNPs) were amplified using nested polymerase chain reaction and detected by sequence specific oligonucleotide probe-enzyme linked immunosorbent assay (SSOP-ELISA). RESULTS: The prevalence of the mutant Pfdhfr-Pfdhps haplotypes was heterogenous and transmission dependent. The triple Pfdhfr mutant haplotypes (CIRNI) were predominant in all sites with significantly higher frequencies at Muheza (93.3 %) compared to Muleba (75.0 %) and Nachingwea districts (70.6 %), (p < 0.001). Overall, the prevalence of the wild-type Pfdhps (SAKAA) haplotype was lowest at Muheza (1.3 %), (p = 0.002). Double Pfdhps haplotype SGEAA was significantly high at Muheza (27.2 %) and Muleba (20.8 %) while none (0 %) was detected at Nachingwea (p < 0.001). The prevalence of triple Pfdhps SGEGA haplotype was significantly higher at Muheza compared to Muleba and Nachingwea (p < 0.001). In contrast, Nachingwea and Muleba had significantly higher prevalence of another triple Pfdhps AGEAA haplotype (chi(2) = 39.9, p < 0.001). Conversely, Pfdhfr Pfdhps as quintuple and sextuple haplotypes were predominant including the emergence of a septuple mutant haplotype CIRNI-AGEGA (n = 11) observed at Muheza and Muleba. CONCLUSION: These results ascertain the high prevalence and saturation of Pfdhfr and Pfdhps haplotypes conferring SP resistance in areas with changing malaria epidemiology; and this could undermine the use of IPTp-SP in improving pregnancy outcomes. In these settings where high level SP resistance is documented, additional control efforts are needed and evaluation of an alternative drug for IPTp is an urgent priority. PMID- 26542944 TI - Resilience, reactivity and variability: A mathematical comparison of ecological stability measures. AB - In theoretical studies, the most commonly used measure of ecological stability is resilience: ecosystems asymptotic rate of return to equilibrium after a pulse perturbation -or shock. A complementary notion of growing popularity is reactivity: the strongest initial response to shocks. On the other hand, empirical stability is often quantified as the inverse of temporal variability, directly estimated on data, and reflecting ecosystems response to persistent and erratic environmental disturbances. It is unclear whether and how this empirical measure is related to resilience and reactivity. Here, we establish a connection by introducing two variability-based stability measures belonging to the theoretical realm of resilience and reactivity. We call them intrinsic, stochastic and deterministic invariability; respectively defined as the inverse of the strongest stationary response to white-noise and to single-frequency perturbations. We prove that they predict ecosystems worst response to broad classes of disturbances, including realistic models of environmental fluctuations. We show that they are intermediate measures between resilience and reactivity and that, although defined with respect to persistent perturbations, they can be related to the whole transient regime following a shock, making them more integrative notions than reactivity and resilience. We argue that invariability measures constitute a stepping stone, and discuss the challenges ahead to further unify theoretical and empirical approaches to stability. PMID- 26542945 TI - EIF2A-dependent translational arrest protects leukemia cells from the energetic stress induced by NAMPT inhibition. AB - BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD(+) biosynthesis from nicotinamide, is one of the major factors regulating cancer cells metabolism and is considered a promising target for treating cancer. The prototypical NAMPT inhibitor FK866 effectively lowers NAD(+) levels in cancer cells, reducing the activity of NAD(+)-dependent enzymes, lowering intracellular ATP, and promoting cell death. RESULTS: We show that FK866 induces a translational arrest in leukemia cells through inhibition of MTOR/4EBP1 signaling and of the initiation factors EIF4E and EIF2A. Specifically, treatment with FK866 is shown to induce 5'AMP-activated protein kinase (AMPK) activation, which, together with EIF2A phosphorylation, is responsible for the inhibition of protein synthesis. Notably, such an effect was also observed in patients' derived primary leukemia cells including T-cell Acute Lymphoblastic Leukemia. Jurkat cells in which AMPK or LKB1 expression was silenced or in which a non phosphorylatable EIF2A mutant was ectopically expressed showed enhanced sensitivity to the NAMPT inhibitor, confirming a key role for the LKB1-AMPK-EIF2A axis in cell fate determination in response to energetic stress via NAD(+) depletion. CONCLUSIONS: We identified EIF2A phosphorylation as a novel early molecular event occurring in response to NAMPT inhibition and mediating protein synthesis arrest. In addition, our data suggest that tumors exhibiting an impaired LBK1- AMPK- EIF2A response may be especially susceptible to NAMPT inhibitors and thus become an elective indication for this type of agents. PMID- 26542946 TI - Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer. AB - BACKGROUND: Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown. OBJECTIVE: Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA. DESIGN, SETTINGS, AND PARTICIPANTS: We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared. RESULTS AND LIMITATIONS: The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied. CONCLUSIONS: HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression. PATIENT SUMMARY: In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA. PMID- 26542947 TI - Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens. AB - BACKGROUND: Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason <= 6, 3 + 4, 4 + 3, 8, and 9 10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer. OBJECTIVE: To assess the clinical relevance of the fractions of Gleason patterns. DESIGN, SETTING, AND PARTICIPANTS: Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. RESULTS AND LIMITATIONS: Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. CONCLUSIONS: Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. PATIENT SUMMARY: Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories <= 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making. PMID- 26542949 TI - Carbapenemase-producing Enterobacteriaceae: use of a dynamic registry of cases and contacts for outbreak management. AB - BACKGROUND: The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health problem. Control and prevention of CPE infections hinge on isolation precautions for carriers and active screening and follow-up of contacts. AIM: To implement an open registry of cases and contacts for acute outbreak management, long-term data collection and epidemiological investigation. METHODS: All cases, defined as patients (infected or colonized) with a CPE-positive culture during their hospitalization, and contacts (e.g. patients cared for by the same healthcare team as a case) were registered in an ongoing database. Hospital stays were cross-referenced for every new entry and epidemiological links (e.g. shared contacts) investigated. All cases and contacts not cleared by complete screening were registered on an active list. FINDINGS: Between October 2012 and November 2014, we registered 30 cases and 1268 contacts, among which 24 were linked to two or three separate cases. Only 6.5% of contacts fulfilled complete screening with three rectal swabs, and 1145 contacts are still registered on the active surveillance list. Two outbreaks (12 and nine cases) occurred nine months apart. Cross-referencing of hospital stays using the registry revealed epidemiological links between seemingly unrelated cases of CPE-positive patients and suggested an environmental source of transmission, which was demonstrated thereafter. CONCLUSION: We implemented a simple and multi-purpose tool to manage CPE episodes and investigate epidemiological links. Efforts are necessary to improve screening of contact patients who may be occult sources of transmission. A regional registry could be helpful. PMID- 26542948 TI - Genetic differences between two Leishmania major-like strains revealed by suppression subtractive hybridization. AB - Leishmania major, the causative agent of zoonotic leishmaniasis, is restricted to Old World countries. Molecular and biochemical techniques have been used to identify some L. major-like isolated in South America including Brazil. Here, two L. major-like strains, one virulent (BH49) and one non-virulent (BH121), were subjected to suppression subtractive hybridization (SSH) technique in order to identify differentially expressed genes. SSH technique identified nine cDNA fragments exhibiting high homology to previously sequenced L. major genes. Five cDNAs (four specific for BH49 and one for BH121) were confirmed by RT-PCR. Among those differentially expressed subtracted genes, some were involved in physiological processes including metabolism, translation and destination of proteins, production of energy, virulence factors and unknown functions. Western blot analysis confirmed a higher expression level of beta-1,3-galactosyl residues in L. major-like lipophosphoglycan (LPG). This molecular analysis opens the possibility for identification of potential virulence factors not only in different strains, but also in others species of Leishmania. PMID- 26542950 TI - Organization of infection control in European hospitals. AB - BACKGROUND: The Prevention of Hospital Infections by Intervention and Training (PROHIBIT) survey was initiated to investigate the status of healthcare associated infection (HCAI) prevention across Europe. AIM: This paper presents the methodology of the quantitative PROHIBIT survey and outlines the findings on infection control (IC) structure and organization including management's support at the hospital level. METHODS: Hospitals in 34 countries were invited to participate between September 2011 and March 2012. Respondents included IC personnel and hospital management. FINDINGS: Data from 309 hospitals in 24 countries were analysed. Hospitals had a median (interquartile range) of four IC nurses (2-6) and one IC doctor (0-2) per 1000 beds. Almost all hospitals (96%) had defined IC objectives, which mainly addressed hand hygiene (87%), healthcare associated infection reduction (84%), and antibiotic stewardship (66%). Senior management provided leadership walk rounds in about half of hospitals, most often in Eastern and Northern Europe, 65% and 64%, respectively. In the majority of hospitals (71%), sanctions were not employed for repeated violations of IC practices. Use of sanctions varied significantly by region (P < 0.001), but not by countries' healthcare expenditure. CONCLUSION: There is great variance in IC staffing and policies across Europe. Some areas of practice, such as hand hygiene, seem to receive considerably more attention than others that are equally important, such as antibiotic stewardship. Programmes in IC suffer from deficiencies in human resources and local policies, ubiquitous factors that negatively impact on IC effectiveness. Strengthening of IC policies in European hospitals should be a public health priority. PMID- 26542951 TI - Outcome of surgery in patients with solitary fibrous tumors of the pleura. AB - BACKGROUND: Solitary fibrous tumor of the pleura is rare, and the origin is submesothelial tissue. These tumors are seen in lung infrequently, and most are benign. We report our experience in the diagnosis and treatment of patients with solitary fibrous tumors of the pleura. METHODS: We studied 13 patients (6 men and 7 women, aged 26 to 76 years) with a diagnosis of benign solitary fibrous tumor of the pleura who were operated on from 2001 to 2014. One had a recurrent tumor after 10 years, and the others had primary tumors. Our approach was complete resection in all cases. RESULTS: After surgical excision, the most essential characteristic on histopathology was a neoplastic lesion composed of spindle shaped tumor cells with hyperchromatic nuclei and eosinophilic bands of collagen. On immunohistochemical analysis, the cells were positive for desmin and negative for actin, synaptophysin, chromogranin, and CD117. CONCLUSIONS: The essential step in the treatment of a patient with a diagnosis of benign solitary fibrous tumor of the pleura is complete resection. These patients should be followed up for a long time because of the possibility of late recurrence. Due to the rarity of these tumors, there has been no systematic assessment of the role of adjuvant therapy for benign solitary fibrous tumor of the pleura. PMID- 26542952 TI - Qualitative real-time analysis by nurses of sublingual microcirculation in intensive care unit: the MICRONURSE study. AB - INTRODUCTION: We aimed to determine i) the feasibility of nurses taking bedside measurements of microcirculatory parameters in real time in intensive care patients; and ii) whether such measurements would be comparable to those obtained by the classical delayed semi quantitative analysis made by a physician. METHODS: This prospective observational study was conducted in a university hospital and was approved by our local Institutional Review Board (IRB 00006477). After ICU admission and study inclusion, a set of measurements of macrocirculatory and microcirculatory parameters was taken by the nurse in charge of the patient every 4 h within the first 12 h after admission and before and after every hemodynamic therapeutic intervention. Seventy-four sublingual microvascular measurements were performed with incident dark field illumination (IDF) microscopy in 20 mechanically ventilated patients hospitalized in the ICU. RESULTS: There were no significant differences between the microvascular flow index (MFI) taken in real time by the nurses and the delayed evaluation by the physician. In fact, the nurses' real-time measurement of MFI demonstrated good agreement with the physician's delayed measurement. The mean difference between the two MFIs was 0.15, SD = 0.28. The nurses' real-time MFI assessment showed 97 % sensitivity (95 % CI: 84-99 %) and 95 % specificity (95 % CI: 84-99 %) at detecting a MFI <2.5 obtained by a physician upon delayed semiquantitative measurement. Concerning the density, 81 % of the paramedical qualitative density measurements corresponded with the automatized total vessel density (TVD) measurements. The nurses' real time TVD assessment showed 77 % sensitivity (95 % CI: 46-95 %) and 100 % specificity (95 % CI: 89-100 %) at detecting a TVD <8 mm/mm(2). CONCLUSION: A real-time qualitative bedside evaluation of MFI by nurses showed good agreement with the conventional delayed analysis by physicians. The bedside evaluations of MFI and TVD were highly sensitive and specific for detecting impaired microvascular flow and low capillary density. These results suggest that this real-time technique could become part of ICU nurse routine surveillance and be implemented in algorithms for hemodynamic resuscitation in future clinical trials and regular practice. These results are an essential step to demonstrate whether these real-time measurements have a clinical impact in the management of ICU patients. PMID- 26542953 TI - The costs of offering HPV-testing on self-taken samples to non-attendees of cervical screening in Finland. AB - BACKGROUND: Offering self-sampling to non-attendees of cervical screening increases screening attendance. METHODS: We used observations from two Finnish studies on the use of self-sampling among the non-attendees to estimate in a hypothetical screening population of 100,000 women the possible costs per extra screened woman and costs per extra detected and treated CIN2+ with three intervention strategies; 1) a primary invitation and a reminder letter, 2) a primary invitation and a mailed self-sampling kit and 3) two invitation letters and a self-sampling kit. The program costs were derived from actual performance and costs in the original studies and a national estimate on management costs of HPV related diseases. RESULTS: The price per extra participant and price per detected and treated CIN2+ lesion was lower with a reminder letter than by self sampling as a first reminder. When self-sampling was used as a second reminder with a low sampler price and a triage Pap-smear as a follow-up test for HPV positive women instead of direct colposcopy referral, the eradication of a CIN2+ lesion by self-sampling was not more expensive than in routine screening, and the addition of two reminders to the invitation protocol did not increase the price of an treated CIN2+ lesion in the entire screened population. CONCLUSIONS: As a first reminder, a reminder letter is most likely a better choice. As second reminder, the higher costs of self-sampling might be compensated by the higher prevalence of CIN2+ in the originally non-attending population. PMID- 26542954 TI - Trends in prevalence of overweight and obesity: are Portuguese adolescents still increasing weight? AB - OBJECTIVE: To report the prevalence and trends of the BMI of Portuguese adolescents in 2002, 2006 and 2010. METHODS: 4138 boys and 4472 girls self reported weight, height, physical activity, perception of health and life satisfaction. RESULTS: For adolescents aged 11-13 years, the prevalence of overweight/obesity decreased from 23.5 % in 2002 to 20.7 % in 2010, using IOTF cutoff points, and decreased from 32.4 to 28.4 % between 2002 and 2010 using WHO cutoff points. For adolescents aged 15-17 years, the prevalence increased from 13.9 to 16.8 % between 2002 and 2010 using IOTF cutoff, and increased from 14.8 % in 2002 to 18.2 % in 2010 when using WHO cutoff points. Although the prevalence decreased among younger adolescents and increased among older ones, the differences were not significant. Physical activity in the last 7 days (p < 0.05), better life satisfaction (p < 0.05) and perception of health (p < 0.001) predicted lower body mass index z score. CONCLUSIONS: Overall, there have been no significant changes in overweight and obesity prevalence in Portuguese adolescents from 2002 to 2010. However, the prevalence remains high and therefore it is important to continue surveillance. PMID- 26542955 TI - Changes in stroke mortality trends and premature mortality due to stroke in Serbia, 1992-2013. AB - OBJECTIVES: To determine mortality trends and premature mortality due to stroke in Serbia in 1992-2013 period. METHODS: We obtained mortality database from the Statistical Office of Serbia. RESULTS: From 1992 to 2005, age-standardized mortality rates (ASRs) per 100,000 for all stroke increased, with annual percentage change (APC) of 1.01 % in men and 1.05 % in women. From 2005 to 2013, ASRs decreased, with APC of -4.93 % in men, and -5.63 % in women. In men, years of life lost (YLLs) for all stroke deaths were 21,710 in 1992; 22,193 in 2003 and 17,464 in 2013, with average years of life lost (AYLLs) of 3.46, 2.89 and 3.00, respectively. In women, YLLs were 33,508 in 1992; 35,130 in 2003 and 21,676 in 2013, with AYLLs of 4.65; 3.57 and 2.97. CONCLUSIONS: From 1992 to 2013, ASRs and YLLs for all stroke showed two segment trends in Serbia, with increase in the first, and decrease in the second period. Due to the shorter AYLLs and longer life tables, in 2013 stroke deaths occurred at >4 years older age in both sexes than in 1992. PMID- 26542957 TI - Capture of Tribolium castaneum and Tribolium confusum (Coleoptera: Tenebrionidae) in Floor Traps: The Effect of Previous Captures. AB - The impact of prior captures on the trapping performance of floor traps was evaluated for the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), and the confused flour beetle, Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae), in laboratory conditions. The effect of trap seeding, adding adults of the same or different species, was evaluated in order to determine possible effects of prior captures in the trap on each species' behavioral responses. The presence of seeded beetles of the same species resulted in an increase in beetle captures for both T. castaneum and T. confusum, but when traps were seeded with the opposite species, there was no increase in beetle captures for either species, and for T. castaneum overall captures in both seeded and unseeded traps was reduced. Overall, T. castaneum tended to have greater captures than T. confusum regardless of the treatment. When the two species were released together, this negated the increased response to seeded traps observed in the single-species treatments. These findings suggest the potential that the presence of beetles in a trap may be influencing the response of beetles in a nearby trap and that T. castaneum and T. confusum when they occur together may influence each other's response to traps. PMID- 26542956 TI - Fertility biomarkers to estimate metabolic risks in women with polycystic ovary syndrome. AB - PURPOSE: We sought to evaluate the relationship between the polycystic ovary syndrome (PCOS)-defining characteristics and the risk of developing metabolic complications in women presenting with complaints of infertility and/or menstrual irregularities and subsequently diagnosed with PCOS. METHODS: This was a cross sectional study. Women presenting with complaints of infertility and/or irregular menses and diagnosed with PCOS by the Rotterdam criteria, underwent endocrine, metabolic, and ultrasound assessment in the early follicular phase. Reproductive and metabolic parameters were included in regression analysis models with the PCOS-defining characteristics; ROC curves were calculated for the significant predictors. RESULTS: Three hundred and seventy-four women with PCOS were included in our study. Oligo-anovulation, menstrual irregularities, and hirsutism were not predictive of any of the variables. Ovarian volume, follicle count, and biochemical hyperandrogenism were predictors for hormonal, metabolic, and endometrial complications. The relationships were independent of age and body mass index. ROC curves identified lower cut-off values of the PCOS-defining characteristics to predict patients' risks of hyperinsulinemia, dyslipidemia, and glucose intolerance. CONCLUSIONS: Adverse metabolic effects of PCOS are already present in women at the time they present complaining of infertility and/or irregular menses. Hyperandrogenism and ultrasound can assist in predicting the patients' concomitant metabolic abnormalities and can aid physicians in tailoring counseling for effective preventive strategies. PMID- 26542958 TI - OsNF-YC2 and OsNF-YC4 proteins inhibit flowering under long-day conditions in rice. AB - MAIN CONCLUSION: OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response through the modulation of three flowering-time genes ( Ehd1, Hd3a , and RFT1 ) in rice. Plant NUCLEAR FACTOR Y (NF-Y) transcription factors control numerous developmental processes by forming heterotrimeric complexes, but little is known about their roles in flowering in rice. In this study, it is shown that some subunits of OsNF-YB and OsNF-YC interact with each other, and among them, OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response of rice. Protein interaction studies showed that the physical interactions occurred between the three OsNF-YC proteins (OsNF-YC2, OsNF-YC4 and OsNF-YC6) and three OsNF-YB proteins (OsNF-YB8, OsNF-YB10 and OsNF-YB11). Repression and overexpression of the OsNF-YC2 and OsNF-YC4 genes revealed that they act as inhibitors of flowering only under long-day (LD) conditions. Overexpression of OsNF-YC6, however, promoted flowering only under LD conditions, suggesting it could function as a flowering promoter. These phenotypes correlated with the changes in the expression of three rice flowering-time genes [Early heading date 1 (Ehd1), Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1)]. The diurnal and tissue-specific expression patterns of the subsets of OsNF-YB and OsNF-YC genes were similar to those of CCT domain encoding genes such as OsCO3, Heading date 1 (Hd1) and Ghd7. We propose that OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response by interacting directly with OsNF-YB8, OsNF-YB10 or OsNF-YB11 proteins in rice. PMID- 26542960 TI - Severe iron deficiency anaemia associated with heavy lice infestation in a young woman. AB - Lice feed on human blood, and heavy and chronic lice infestation can lead to chronic blood loss with resultant iron deficiency anaemia. Although no definite relationship between lice infestation and iron deficiency anaemia has been described, the concurrent presence of these two conditions has been reported in children and adults, as well as in cattle. We present a case of a young woman with severe iron deficiency anaemia that could not be explained by the known causes of iron deficiency anaemia. However, the patient was found to have heavy and chronic head lice infestation. PMID- 26542959 TI - Conditional knockout of Foxc2 gene in kidney: efficient generation of conditional alleles of single-exon gene by double-selection system. AB - Foxc2 is a single-exon gene and a key regulator in development of multiple organs, including kidney. To avoid embryonic lethality of conventional Foxc2 knockout mice, we conditionally deleted Foxc2 in kidneys. Conditional targeting of a single-exon gene involves the large floxed gene segment spanning from promoter region to coding region to avoid functional disruption of the gene by the insertion of a loxP site. Therefore, in ES cell clones surviving a conventional single-selection, e.g., neomycin-resistant gene (neo) alone, homologous recombination between the long floxed segment and target genome results in a high incidence of having only one loxP site adjacent to the selection marker. To avoid this limitation, we employed a double-selection system. We generated a Foxc2 targeting construct in which a floxed segment contained 4.6 kb mouse genome and two different selection marker genes, zeocin resistant gene and neo, that were placed adjacent to each loxP site. After double selection by zeocin and neomycin, 72 surviving clones were screened that yielded three correctly targeted clones. After floxed Foxc2 mice were generated by tetraploid complementation, we removed the two selection marker genes by a simultaneous-single microinjection of expression vectors for Dre and Flp recombinases into in vitro-fertilized eggs. To delete Foxc2 in mouse kidneys, floxed Foxc2 mice were mated with Pax2-Cre mice. Newborn Pax2-Cre; Foxc2(loxP/loxP) mice showed kidney hypoplasia and glomerular cysts. These results indicate the feasibility of generating floxed Foxc2 mice by double selection system and simultaneous removal of selection markers with a single microinjection. PMID- 26542961 TI - Porcine liver vascular bed in Biodur E20 corrosion casts. AB - BACKGROUND: Pigs are frequently used as animal models in experimental medicine. To identify processes of vascular development or regression, vascular elements must be recognised and quantified in a three-dimensional (3D) arrangement. Vascular corrosion casts enable the creation of 3D replicas of vascular trees. The aim of our study was to identify suitable casting media and optimise the protocol for porcine liver vascular corrosion casting. MATERIALS AND METHODS: Mercox II(r) (Ladd Research, Williston, Vermont, USA) and Biodur E20(r) Plus (Biodur Products, Heidelberg, Germany) were tested in 4 porcine livers. The resins (volume approximately 700 mL) were injected via the portal vein. Corrosion casts were examined by macro-computed tomography, micro-computed tomography and scanning electron microscopy. RESULTS: For hepatectomies, the operating protocol was optimised to avoid gas or blood clot embolisation. We present a protocol for porcine liver vascular bed casting based on corrosion specimens prepared using Biodur E20(r) epoxy resin. CONCLUSIONS: Only Biodur E20(r)Plus appeared to be suitable for high-volume vascular corrosion casting due to its optimal permeability, sufficient processing time and minimum fragility. Biodur E20(r) Plus is slightly elastic, radio-opaque and alcohol-resistant. These properties make this acrylic resin suitable for not only vascular research but also teaching purposes. PMID- 26542962 TI - Clinical anatomy and clinical significance of the cervical intervertebral foramen: a review. AB - The aim of this paper is to summarise the knowledge about the anatomy of the cervical intervertebral foramen as a whole. Such reviews are rare in the literature. The intervertebral or neural foramen is the opening between the spinal canal and the extraspinal region. It is located between the vertebral pedicles at all spinal levels. A number of structures pass through the foramen: nerves, vessels and ligaments. We describe the bony borders and dimensions of the foramen, the adjacent ligaments, the arteries and veins passing through or neighbouring it, and the neural components. Many procedures are performed in the area of the cervical intervertebral foramen. Knowledge of the anatomy of the foramen is essential in order to operate to the area and to minimize iatrogenic injuries. PMID- 26542963 TI - Cone beam computed tomography investigation of the antral artery anastomosis in a population of Central Italy. AB - BACKGROUND: The arterial vascular supply of maxillary sinus has to be considered in all the surgical procedures where it is involved. In particular, the intraosseous anastomosis between the posterior superior alveolar artery and the infraorbital artery branches in the bony canal can be tricky to a not well aware clinician. The aim of this study is to investigate the arterial blood supply of the maxillary sinus to give clinicians the basis for a better understanding of vascular complications that can derive from surgical procedures at this level. MATERIALS AND METHODS: One hundred cone beam computed tomography were analysed by the Imaging software for three-dimensional images, i-Dixel 2.0. The parameters considered have been the presence (i), the calibre (ii), the dorso-ventral length (iii) and the cranio-caudal distance (iv). The data have been processed with means, standard deviations and verified by T-Student test. RESULTS: The statistical outputs showed that the 38% of samples presented the intraosseous anastomosis. Those anastomosis resulted long in dorso-ventral way both on left (12.55 +/- 4.3 mm) and right side (12.4 +/- 4.3 mm). The mean cranio- -caudal distance resulted 15.71 +/- 5.08 mm on the left and 14.73 +/- 4.74 mm on right side. The calibre measurements resulted quite big as well: 1.68 +/- 0.3 mm on the left and 1.54 +/- 0.38 mm on the right. The differences between the right and left sides were found not statistically significant. CONCLUSIONS: This in vivo investigation shows how a knowledge of the maxillary sinus vascularisation is essential during the programming surgical phase in order to prevent blood complications during the operations involving this region. (. PMID- 26542964 TI - Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes. AB - A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25MUM against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU 145 cell line and Gram negative bacterial strains. PMID- 26542965 TI - Divinyl BODIPY derivative: Synthesis, photophysical properties, crystal structure, photostability and bioimaging. AB - 4,4-Difluoro-3,5-bis(3,3-dimethyl-1-butenyl)-8-anthryl-4-bora-3a,4a-diaza-s indacene (1), a symmetric fluorescent difluoroboron dipyrromethene dye, was produced in Knoevenagel reaction involving 4,4-difluoro-3,5-bis(methyl)-8-anthryl 4-bora-3a,4a-diaza-s-indacene (2) and pivaldehyde. Its crystal structure was determined by single crystal X-ray diffraction analysis, and the photophysical properties were investigated. The BODIPY 1 exhibits significant bathochromic shifts in both absorption and fluorescence spectrum compared with the BODIPY 2. In addition, the BODIPY 1 exhibited small energy gaps (2.11eV). The extensive pi conjugation is responsible for their red-shifted emission. Cell imaging experiments demonstrated its potential application as a biological fluorescent probe due to its excellent imaging contrast. PMID- 26542966 TI - Novel orally active inhibitors of beta-1,3-glucan synthesis derived from enfumafungin. AB - The clinical success of the echinocandins, which can only be administered parentally, has validated beta-1,3-glucan synthase (GS) as an antifungal target. Semi-synthetic modification of enfumafungin, a triterpene glycoside natural product, was performed with the aim of producing a new class of orally active GS inhibitors. Replacement of the C2 acetoxy moiety with various heterocycles did not improve GS or antifungal potency. However, replacement of the C3 glycoside with an aminoether moiety dramatically improved oral pharmacokinetic (PK) properties while maintaining GS and antifungal potency. Installing an aminotetrazole at C2 in conjunction with an N-alkylated aminoether at C3 produced derivatives with significantly improved GS and antifungal potency that exhibited robust oral efficacy in a murine model of disseminated candidiasis. PMID- 26542968 TI - Role of computed tomography angiography and perfusion tomography in diagnosing brain death: A systematic review. AB - BACKGROUND: Several complications make the diagnosis of brain death (BD) medically challenging and a complimentary method is needed for confirmation. In this context, computed tomography angiography (CTA) and computed tomography perfusion (CTP) could represent valuable alternatives; however, the reliability of CTA and CTP for confirming brain circulatory arrest remains unclear. METHODS: A systematic review was performed to identify relevant studies regarding the use of CTA and CTP as ancillary tests for BD confirmation. RESULTS: Three hundred twenty-two patients were eligible for the meta-analysis, which exhibited 87.5% sensitivity. CTA image evaluation protocol exhibited variations between medical institutions regarding which intracranial vessels should be considered to determine positive or negative test results. CONCLUSIONS: For patients who were previously diagnosed with BD according to clinical criteria, CTA demonstrated high sensitivity to provide radiologic confirmation. The current evidence that supports the use of CTA in BD diagnosis is comparable to other methods applied worldwide. PMID- 26542967 TI - Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X. AB - Influenza viruses isolated from ducks are rarely able to infect chickens; it is therefore postulated that these viruses need to adapt in some way to be able to be transmitted to chickens in nature. Previous studies revealed that sialyl Lewis X (3'SLeX), which is fucosylated alpha2,3 sialoside, was predominantly detected on the epithelial cells of the chicken trachea, whereas this glycan structure is not found in the duck intestinal tract. To clarify the mechanisms of the interspecies transmission of influenza viruses between ducks and chickens, we compared the receptor specificity of low-pathogenic avian influenza viruses isolated from these two species. Glycan-binding analysis of the recombinant hemagglutinin (HA) of a chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2), revealed a binding preference to alpha1,3 fucosylated sialosides. On the other hand, the HA of a duck influenza virus, A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG), particularly bound to non-fucosylated alpha2,3 sialosides such as 3' sialyllactosamine (3'SLacNAc). Computational analysis along with binding analysis of the mutant HAs revealed that this glycan-binding specificity of the HA was determined by amino acid residues at positions 222 and 227. Inconsistent with the glycan-binding specificity of the recombinant HA protein, virions of Dk/MNG bound to both 3'SLacNAc and 3'SLeX. Glycan-binding analysis in the presence of a neuraminidase (NA) inhibitor revealed that the NA conferred binding to 3'SLeX to virions of Dk/MNG. The present results reveal the molecular basis of the interaction between fucosylated alpha2,3 sialosides and influenza viruses. PMID- 26542969 TI - Spanish norms for affective and lexico-semantic variables for 1,400 words. AB - Studies of semantic variables (e.g., concreteness) and affective variables (i.e., valence and arousal) have traditionally tended to run in different directions. However, in recent years there has been growing interest in studying the relationship, as well as the potential overlaps, between the two. This article describes a database that provides subjective ratings for 1,400 Spanish words for valence, arousal, concreteness, imageability, context availability, and familiarity. Data were collected online through a process involving 826 university students. The results showed a high interrater reliability for all of the variables examined, as well as high correlations between our affective and semantic values and norms currently available in other Spanish databases. Regarding the affective variables, the typical quadratic correlation between valence and arousal ratings was obtained. Likewise, significant correlations were found between the lexico-semantic variables. Importantly, we obtained moderate negative correlations between emotionality and both concreteness and imageability. This is in line with the claim that abstract words have more affective associations than concrete ones (Kousta, Vigliocco, Vinson, Andrews, & Del Campo, 2011). The present Spanish database is suitable for experimental research into the effects of both affective properties and lexico-semantic variables on word processing and memory. PMID- 26542970 TI - A dyadic stimulus set of audiovisual affective displays for the study of multisensory, emotional, social interactions. AB - We describe the creation of the first multisensory stimulus set that consists of dyadic, emotional, point-light interactions combined with voice dialogues. Our set includes 238 unique clips, which present happy, angry and neutral emotional interactions at low, medium and high levels of emotional intensity between nine different actor dyads. The set was evaluated in a between-design experiment, and was found to be suitable for a broad potential application in the cognitive and neuroscientific study of biological motion and voice, perception of social interactions and multisensory integration. We also detail in this paper a number of supplementary materials, comprising AVI movie files for each interaction, along with text files specifying the three dimensional coordinates of each point light in each frame of the movie, as well as unprocessed AIFF audio files for each dialogue captured. The full set of stimuli is available to download from: http://motioninsocial.com/stimuli_set/ . PMID- 26542971 TI - Tap Arduino: An Arduino microcontroller for low-latency auditory feedback in sensorimotor synchronization experiments. AB - Timing abilities are often measured by having participants tap their finger along with a metronome and presenting tap-triggered auditory feedback. These experiments predominantly use electronic percussion pads combined with software (e.g., FTAP or Max/MSP) that records responses and delivers auditory feedback. However, these setups involve unknown latencies between tap onset and auditory feedback and can sometimes miss responses or record multiple, superfluous responses for a single tap. These issues may distort measurements of tapping performance or affect the performance of the individual. We present an alternative setup using an Arduino microcontroller that addresses these issues and delivers low-latency auditory feedback. We validated our setup by having participants (N = 6) tap on a force-sensitive resistor pad connected to the Arduino and on an electronic percussion pad with various levels of force and tempi. The Arduino delivered auditory feedback through a pulse-width modulation (PWM) pin connected to a headphone jack or a wave shield component. The Arduino's PWM (M = 0.6 ms, SD = 0.3) and wave shield (M = 2.6 ms, SD = 0.3) demonstrated significantly lower auditory feedback latencies than the percussion pad (M = 9.1 ms, SD = 2.0), FTAP (M = 14.6 ms, SD = 2.8), and Max/MSP (M = 15.8 ms, SD = 3.4). The PWM and wave shield latencies were also significantly less variable than those from FTAP and Max/MSP. The Arduino missed significantly fewer taps, and recorded fewer superfluous responses, than the percussion pad. The Arduino captured all responses, whereas at lower tapping forces, the percussion pad missed more taps. Regardless of tapping force, the Arduino outperformed the percussion pad. Overall, the Arduino is a high-precision, low-latency, portable, and affordable tool for auditory experiments. PMID- 26542972 TI - Reaction time effects in lab- versus Web-based research: Experimental evidence. AB - Although Web-based research is now commonplace, it continues to spur skepticism from reviewers and editors, especially whenever reaction times are of primary interest. Such persistent preconceptions are based on arguments referring to increased variation, the limits of certain software and technologies, and a noteworthy lack of comparisons (between Web and lab) in fully randomized experiments. To provide a critical test, participants were randomly assigned to complete a lexical decision task either (a) in the lab using standard experimental software (E-Prime), (b) in the lab using a browser-based version (written in HTML and JavaScript), or (c) via the Web using the same browser-based version. The classical word frequency effect was typical in size and corresponded to a very large effect in all three conditions. There was no indication that the Web- or browser-based data collection was in any way inferior. In fact, if anything, a larger effect was obtained in the browser-based conditions than in the condition relying on standard experimental software. No differences between Web and lab (within the browser-based conditions) could be observed, thus disconfirming any substantial influence of increased technical or situational variation. In summary, the present experiment contradicts the still common preconception that reaction time effects of only a few hundred milliseconds cannot be detected in Web experiments. PMID- 26542973 TI - Promises and pitfalls of Web-based experimentation in the advance of replicable psychological science: A reply to Plant (2015). AB - In a recent letter, Plant (2015) reminded us that proper calibration of our laboratory experiments is important for the progress of psychological science. Therefore, carefully controlled laboratory studies are argued to be preferred over Web-based experimentation, in which timing is usually more imprecise. Here we argue that there are many situations in which the timing of Web-based experimentation is acceptable and that online experimentation provides a very useful and promising complementary toolbox to available lab-based approaches. We discuss examples in which stimulus calibration or calibration against response criteria is necessary and situations in which this is not critical. We also discuss how online labor markets, such as Amazon's Mechanical Turk, allow researchers to acquire data in more diverse populations and to test theories along more psychological dimensions. Recent methodological advances that have produced more accurate browser-based stimulus presentation are also discussed. In our view, online experimentation is one of the most promising avenues to advance replicable psychological science in the near future. PMID- 26542974 TI - Quantifying online visuomotor feedback utilization in the frequency domain. AB - The utilization of sensory information during activities of daily living is ubiquitous both prior to and during movements (i.e., related to planning and online control, respectively). Because of the overlapping nature of online corrective processes, the quantification of feedback utilization has proven difficult. In the present study, we primarily sought to evaluate the utility of a novel analysis in the frequency domain for identifying visuomotor feedback utilization (i.e., online control). A second goal was to compare the sensitivity of the frequency analysis to that of currently utilized measures of online control. Participants completed reaching movements to targets located 27, 30, and 33 cm from a start position. During these reaches, vision of the environment was either provided or withheld. Performance was assessed across contemporary measures of online control. For the novel frequency analysis presented in this study, the acceleration profiles of reaching movements were detrended with a 5th order polynomial fit, and the proportional power spectra were computed from the residuals of these fits. The results indicated that the use of visual feedback during reaching movements increased the contribution of the 4.68-Hz frequency to the residuals of the acceleration profiles. Comparisons across all measures of online control showed that the most sensitive measure was the squared Fisher transform of the correlation between the positions at 75 % and 100 % of the movement time. However, because such correlational measures can be contaminated by offline control processes, the frequency-domain analysis proposed herein represents a viable and promising alternative to detect changes in online feedback utilization. PMID- 26542975 TI - Hierarchical Bayesian estimation and hypothesis testing for delay discounting tasks. AB - A state-of-the-art data analysis procedure is presented to conduct hierarchical Bayesian inference and hypothesis testing on delay discounting data. The delay discounting task is a key experimental paradigm used across a wide range of disciplines from economics, cognitive science, and neuroscience, all of which seek to understand how humans or animals trade off the immediacy verses the magnitude of a reward. Bayesian estimation allows rich inferences to be drawn, along with measures of confidence, based upon limited and noisy behavioural data. Hierarchical modelling allows more precise inferences to be made, thus using sometimes expensive or difficult to obtain data in the most efficient way. The proposed probabilistic generative model describes how participants compare the present subjective value of reward choices on a trial-to-trial basis, estimates participant- and group-level parameters. We infer discount rate as a function of reward size, allowing the magnitude effect to be measured. Demonstrations are provided to show how this analysis approach can aid hypothesis testing. The analysis is demonstrated on data from the popular 27-item monetary choice questionnaire (Kirby, Psychonomic Bulletin & Review, 16(3), 457-462 2009), but will accept data from a range of protocols, including adaptive procedures. The software is made freely available to researchers. PMID- 26542976 TI - Former drug firm president is charged with masterminding kickback scheme for physicians. PMID- 26542978 TI - Differential regulation by AMP and ADP of AMPK complexes containing different gamma subunit isoforms. AB - The gamma subunits of heterotrimeric AMPK complexes contain the binding sites for the regulatory adenine nucleotides AMP, ADP and ATP. We addressed whether complexes containing different gamma isoforms display different responses to adenine nucleotides by generating cells stably expressing FLAG-tagged versions of the gamma1, gamma2 or gamma3 isoform. When assayed at a physiological ATP concentration (5 mM), gamma1- and gamma2-containing complexes were allosterically activated almost 10-fold by AMP, with EC50 values one to two orders of magnitude lower than the ATP concentration. By contrast, gamma3 complexes were barely activated by AMP under these conditions, although we did observe some activation at lower ATP concentrations. Despite this, all three complexes were activated, due to increased Thr(172) phosphorylation, when cells were incubated with mitochondrial inhibitors that increase cellular AMP. With gamma1 complexes, activation and Thr(172) phosphorylation induced by the upstream kinase LKB1 [liver kinase B1; but not calmodulin-dependent kinase kinase (CaMKKbeta)] in cell free assays was markedly promoted by AMP and, to a smaller extent and less potently, by ADP. However, effects of AMP or ADP on activation and phosphorylation of the gamma2 and gamma3 complexes were small or insignificant. Binding of AMP or ADP protected all three gamma subunit complexes against inactivation by Thr(172) dephosphorylation; with gamma2 complexes, ADP had similar potency to AMP, but with gamma1 and gamma3 complexes, ADP was less potent than AMP. Thus, AMPK complexes containing different gamma subunit isoforms respond differently to changes in AMP, ADP or ATP. These differences may tune the responses of the isoforms to fit their differing physiological roles. PMID- 26542979 TI - miR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors. AB - Irreversible respiratory obstruction resulting from progressive airway damage, inflammation and fibrosis is a feature of several chronic respiratory diseases, including cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The cytokine transforming growth factor beta (TGF-beta) has a pivotal role in promoting lung fibrosis and is implicated in respiratory disease severity. In the present study, we show that a previously uncharacterized miRNA, miR-1343, reduces the expression of both TGF-beta receptor 1 and 2 by directly targeting their 3'-UTRs. After TGF-beta exposure, elevated intracellular miR-1343 significantly decreases levels of activated TGF-beta effector molecules, pSMAD2 (phosphorylated SMAD2) and pSMAD3 (phosphorylated SMAD3), when compared with a non-targeting control miRNA. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR 1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. miR-1343 may have direct therapeutic applications in fibrotic lung disease. PMID- 26542981 TI - Esophageal submucosal gland duct adenoma: a clinicopathological and immunohistochemical study with a review of the literature. AB - Esophageal submucosal gland duct adenoma (ESGDA) is a rare tumor. The clinicopathological features of the ESGDA and its precursor lesion have not been comprehensively evaluated. In this study, we aimed at delineating the clinicopathological features of the ESGDA and cyst formation of the esophageal submucosal gland duct (ESGD), as well as their correlations and clinical implications. We identified three cases of ESGDA and 16 cases of cyst formation of the ESGD among 786 endoscopic mucosal resection specimens over a 7-year period. The median patient age was 58 years with a male predominance. These lesions were small submucosal bulges locating at the lower esophagus with a size no more than 1 cm. The main microscopic changes of these lesions included content retention, multilayered epithelium or papillary folds of the ESGD and inflammatory cell infiltration, acidophilic degeneration, hyperplasia or atrophy of the acini. The included cases generally showed moderate to severe microscopic esophagitis. The ESGDA was mainly consisted by multiple glandular cysts covered by two layers of cells. Immunohistochemical results showed that the luminal duct lining cells and basal cells were positive for CK7 and p63, respectively. Both of the two layer cells were positive for HMWCK and negative for CK20, p53, CDX2, MUC5AC, MUC6, MUC2 and MUC1. The proliferation index was very low (1%). The diagnostic criteria of the ESGDA were proposed and, the differential diagnosis was discussed. Cyst formation of the ESGD is considered to be the precursor lesion of the ESGDA, because they have overlapping clinicopathological features with progressive relationship. In addition, the ESGDA have close connection with advance of the GERD and, probably, an increased risk of carcinoma. PMID- 26542980 TI - Giant peroxisomes in a moss (Physcomitrella patens) peroxisomal biogenesis factor 11 mutant. AB - Peroxisomal biogenesis factor 11 (PEX11) proteins are found in yeasts, mammals and plants, and play a role in peroxisome morphology and regulation of peroxisome division. The moss Physcomitrella patens has six PEX11 isoforms which fall into two subfamilies, similar to those found in monocots and dicots. We carried out targeted gene disruption of the Phypa_PEX11-1 gene and compared the morphological and cellular phenotypes of the wild-type and mutant strains. The mutant grew more slowly and the development of gametophores was retarded. Mutant chloronemal filaments contained large cellular structures which excluded all other cellular organelles. Expression of fluorescent reporter proteins revealed that the mutant strain had greatly enlarged peroxisomes up to 10 MUm in diameter. Expression of a vacuolar membrane marker confirmed that the enlarged structures were not vacuoles, or peroxisomes sequestered within vacuoles as a result of pexophagy. Phypa_PEX11 targeted to peroxisome membranes could rescue the knock out phenotype and interacted with Fission1 on the peroxisome membrane. Moss PEX11 functions in peroxisome division similar to PEX11 in other organisms but the mutant phenotype is more extreme and environmentally determined, making P. patens a powerful system in which to address mechanisms of peroxisome proliferation and division. PMID- 26542982 TI - Azaphilic versus Carbophilic Coupling at C=N Bonds: Key Steps in Titanium Assisted Multicomponent Reactions. AB - Consecutive C- and N-arylation of N-heterocyclic nitriles is mediated by titanium(IV) alkoxides. The carbo- and azaphilic arylation step may be separated by choosing the order in which the two equivalents of aryl transfer reagent are added. In the course of this transformation, the ancillary N-heterocycle acts as both a directing anchor group and electron reservoir. In the selectivity determining step, the selectivity is governed by a choice between (direct) C- and Ti-arylation; the latter opens up a reaction pathway that allows further migration to the nitrogen atom. The isolation of metal-containing aggregates from the reaction mixture and computational studies gave insights into the reaction mechanism. Subsequently, a multicomponent one-pot protocol was devised to rapidly access complex quaternary carbon centers. PMID- 26542977 TI - Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems. AB - Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. PMID- 26542983 TI - Pattern-Reversal Visual Evoked Potential Parameters and Migraine in the Teenage Population. AB - Although migraine represents one of the most common form of primary headache in the teenage population, most neurophysiologic studies are only on the adulthood. We investigated 38 teenage patients with migraine with aura, 17 male and 21 female, with a mean age of 16.2 years, comparing them with gender- and age matched patients with migraine without aura and healthy subjects. Also, characteristics of aura were correlated with pattern-reversal visual evoked potential parameters. There was a significant difference in left and right eye N2 wave latencies between migraine with aura and migraine without aura patients or healthy controls. In migraine with aura and migraine without aura, 26.3% of patients had abnormal wave latency. Reported tunnel vision during the aura was correlated with lower N1P1 and/or P1N2 wave amplitudes. Also, higher amplitude in patients with migraine with aura correlated with younger age and earlier disease onset, whereas longer aura duration correlated with prolonged wave latency. Findings suggest that migraine subtypes may be differentiated on the basis of N2 wave latency prolongation. PMID- 26542984 TI - Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration Resistant Prostate Cancer. AB - LESSONS LEARNED: Temsirolimus maintenance therapy after docetaxel induction chemotherapyis safe in patients with castration-resistant prostate cancer, although biochemical or tumor responses are rare;does not diminish quality of life; anddelays radiological and/or symptomatic progression by approximately 6 months. BACKGROUND: No standard therapy is available for men with castration resistant prostate cancer (CRPC) who have responded to docetaxel and do not yet have disease progression. Hence, we designed a single-arm phase II trial to explore whether the mTOR inhibitor temsirolimus can maintain the response to docetaxel without compromising quality of life. METHODS: After successful docetaxel induction (75 mg/m(2) every 3 weeks; 6-10 cycles), 21 CRPC patients underwent temsirolimus maintenance treatment (25 mg weekly; 4 weeks per cycle). The primary endpoint was the time to treatment failure (TTTF) (i.e., radiological and/or symptomatic progression). The secondary endpoints included the tumor response rate (RECIST 1.0), safety (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0), quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]), pain (Present Pain Intensity [PPI] scale), prostate-specific antigen (PSA) parameters, including time to PSA progression (TTPP) according to Prostate Cancer Clinical Trials Working Group criteria, and serial enumeration of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs). RESULTS: Patients received a median of 7 cycles of temsirolimus (range, 1-28), resulting in a median TTTF of 24.3 weeks (95% confidence interval [CI], 16.1-33.0), 1 partial tumor response (4.8%), 1 PSA response (4.8%), and a median TTPP of 12.2 weeks (95% CI, 7.8-23.9). Grade 3-4 adverse events were infrequent, and FACT-P and PPI scores remained stable during treatment. CECs did not predict clinical benefit, and CEPs were not consistently detectable. CONCLUSION: Temsirolimus maintenance therapy after successful docetaxel induction is feasible, does not adversely affect quality of life, and, in this exploratory single-arm phase II study, resulted in a median TTTF of 24.3 weeks. PMID- 26542985 TI - Button hole hernioplasty: A new technique for treatment of umblical hernia in cirrhotic patients. A prospective follow up study. AB - BACKGROUND: Surgical treatment of umbilical hernia in cirrhotic patients is still an interesting topic in many studies to achieve the best method of treatment. These patients are liable to many surgical and medical risks. AIMS: to evaluate the surgical outcome as well as the postoperative course of Button hole hernioplasty as a simple, safe, and effective new technique for hernia repair in cirrhotic patients. METHODS: Forty cirrhotic patients with uncomplicated umbilical hernia were included in this study through collaboration between Departments of General Surgery and Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, during one year period. Patients were categorized according to the severity of liver cirrhosis into three groups (A, B, and C). Patients were subjected to an elective hernioplasty after adjustment of the disturbed medical and biochemical factors. RESULTS: There was a significant difference in operative time, hospital stay, and prothrombine (time and concentration) among the three groups (p < 0.05). The three parameters were longest in group C when compared to the other two groups. No severe complications were recorded except in only one case. Also, no recurrence, no morbidities or deaths were recorded after 6 months follow-up. CONCLUSIONS: Button hole hernioplasty is a new simple surgical technique for treatment of umbilical hernia in cirrhotic patients with no significant complications. PMID- 26542986 TI - Seizure outcome following primary motor cortex-sparing resective surgery for perirolandic focal cortical dysplasia. AB - OBJECTIVES: We present a case series of patients who underwent perirolandic resection for medically refractory focal epilepsy due to focal cortical dysplasia (FCD). Our aim was to specifically evaluate the outcome of a surgical strategy intended for seizure freedom while preserving primary motor cortex function. MATERIALS AND METHODS: Thirteen patients undergoing perirolandic resection for pharmacoresistant focal epilepsy between 2010 and 2015 who demonstrated histological evidence of FCD were selected from a prospectively maintained database. Presurgical evaluation included video EEG telemetry and 3T MRI brain for all patients. Eight patients underwent interictal FDG PET scan. Intracranial EEG monitoring was done for 8 patients - six by conventional subdural grid and depth electrodes and two by Stereo EEG. Additional techniques included extraoperative cortical stimulation mapping, intraoperative electrocorticography (ECoG), intraoperative motor cortex mapping and awake surgery in various combinations. In all cases (lesional and nonlesional), resection was intentionally limited for anatomic preservation of the primary motor cortex. RESULTS: Amongst the thirteen patients with age ranging 14-44 years (mean 26.8 +/ 9.2) 62% of them had daily seizures. MRI abnormalities were identified in 8 patients (62%), PET showed concordant findings in 7 patients (88%). When utilized, the mean duration of intracranial EEG recordings was 8.0 +/- 7.2 days (range 2-23 days). All patients underwent a primary motor cortex-sparing resection of the suspected epileptogenic cortex. The mean postoperative follow up period was 23 months (range 7.5-62 months). Twelve out of 13 (92%) were seizure free (Engel 1) outcome at the last follow-up assessment; one patient had Engel 2a outcome at 28 months. Six patients (46%) had immediate new focal neurological deficits, however all six patients had recovered completely within three months. CONCLUSION: The surgical strategy of a primary motor cortex-sparing resective surgery for perirolandic FCD is associated with an excellent early seizure freedom rate and no permanent neurological deficits. Since the ultimate goal of resective epilepsy surgery is seizure freedom with simultaneous functional preservation, similar long term outcome studies should ultimately guide the resection strategy. PMID- 26542987 TI - Surgical treatment of dorsal perilunate fracture-dislocations and prognostic factors. AB - INTRODUCTION: Perilunate injuries are rare entities which can be difficult to diagnose. Most common type is dorsal perilunate fracture dislocation (97%). The purpose of treatment is anatomic reduction and stable fixation. We aimed to present the radiologic and functional results of surgically treated dorsal perilunate fracture-dislocations and discuss the factors influencing the prognosis. METHODS: Between 2007 and 2013, 17 patients were operated for perilunate fracture-dislocations. The mechanism of injuries, soft tissue traumas, etiologic factors and stages according to Herzberg classification were determined. The MAYO wrist score was used for functional evaluation. Scapholunate distance and scapholunate angle were measured and, degenerative changes were investigated by comparing with contralateral side on plain x-ray images in terms of radiologic evaluation. RESULTS: Mean follow-up was 37,8 (range, 16-84) months. The average age at surgery was 35.1 (range, 18-51) years. Fifteen patients were male and two were female. Functional results were excellent in four (23.5%), good in two (11.8%), satisfactory in five (29.4%) and poor in six (35.3%) patients. Degenerative changes were determined in radiocarpal and mid-carpal joints of 14 wrists (82.4%). Scapholunate dissociation more than 2 mm was detected in three wrists. In four wrists osteochondral fragments were determined on the head of the capitate. Stage 2 lesions, delayed presentations, open fractures, scapholunate dissociations more than 2 mm had worse functional results. CONCLUSION: Despite anatomic reduction, ligamentous and chondral injuries that occured at the time of trauma may cause persistant wrist pain in patients who suffer perilunate fracture dislocation. Mechanism of injury, presence of soft tissue defects and the time between injury and treatment can affect clinical and radiologic results. PMID- 26542988 TI - Patient selection for laparoscopic excision of adrenal metastases: A multicenter cohort study. AB - INTRODUCTION: The use of laparoscopy for the excision of adrenal metastasis remains controversial. We aimed to report oncological and perioperative outcomes of laparoscopic excision of adrenal metastases and to seek for predictive factors of unfavorable oncological outcomes. METHODS: A retrospective chart review was conducted and all consecutive patients who underwent laparoscopic adrenalectomy (LA) in the setting of metastatic cancer in two academic urology departments from November 2006 through January 2014 were included. Primary tumors were categorized as pulmonary, renal or "other primary" tumors to allow statistical comparison. Unfavorable surgical outcomes were defined as the occurrence of either postoperative complications and/or positive surgical margins. RESULTS: Forty three patients who underwent a total of 45 LA were included for analysis. There were 8 complications (17.8%). Positive surgical margins were found in 12 specimens (26.7%). After a median follow-up of 37 months, estimated overall survival rates were 89.5% and 51.5% at 1 year and 5 years, respectively. In multivariable analysis the only predictor of unfavorable surgical outcomes was a tumor size >5 cm (OR = 20.5; p = 0.001). In multivariate analysis the pulmonary (OR = 0.3; p = 0.008) or "other" (OR = 0.1; p = 0.0006) origin of the primary tumor was the only prognostic factor of shorter cancer specific survival. CONCLUSION: Laparoscopic resection of adrenal metastasis can be safely performed in most patients but is associated with an increased risk of positive surgical margins and postoperative complications in larger tumors (>5 cm). Adrenalectomy provides better oncological outcomes in metastases from renal cell carcinoma compared to other primary tumors. PMID- 26542989 TI - Role of imaging in cardiac amyloidosis: An ongoing challenge. PMID- 26542990 TI - A useful and easy to develop combined stress test for myocardial perfusion imaging: Regadenoson and isometric exercise, preliminary results. AB - BACKGROUND: Regadenoson, a selective A2a receptor agonist, is a vasodilator increasingly used in myocardial perfusion imaging. Adjunction of isometric exercise is a simple method that could improve side effect profile while providing better image quality. METHODS: Patients undergoing SPECT MPI were prospectively enrolled in handgrip-Regadenoson (HG-Reg test, N = 20) and Regadenoson (Reg) stress test (N = 40). Investigator blinded to stress test analyzed clinical data and images. RESULTS: Heart rate (HR) increase was statistically higher in the HG-Reg group (27 vs 22 bpm, P = .019). Decrease in SBP was less frequent in the HG-Reg group than in the Reg group (55% vs 85.5%, P = .005), there were less drops >10 mmHg (45% vs 77.7%, P = .012). During stress testing, fewer subjects reported at least one side effect in the HG-Reg compared to Reg group (70% vs 92.5%, P = .021). Images were more often classified as good in the HG-Reg group (75% vs 52.5% in the Reg group, P = .25). CONCLUSIONS: Adjunction of handgrip exercise to Regadenoson administration is a well-tolerated and easy method, without loss of time. Furthermore, image quality seems to be better. PMID- 26542991 TI - Review of cardiovascular imaging in the journal of nuclear cardiology in 2015. Part 1 of 2: Plaque imaging, positron emission tomography, computed tomography, and magnetic resonance. AB - In 2015, many original articles pertaining to cardiovascular imaging with impressive quality were published in the Journal of Nuclear Cardiology. In a set of 2 articles, we provide an overview of these contributions to facilitate for the interested reader a quick review of the advancements that occurred in the field over this year. In this first article, we focus on arterial plaque imaging, cardiac positron emission tomography, computed tomography, and magnetic resonance imaging. PMID- 26542992 TI - Debate: Molecular cardiac imaging is ready for the prime time con between wishful thinking and reality. PMID- 26542993 TI - Molecular cardiovascular imaging is ready for prime time: almost there. PMID- 26542994 TI - Pessimistic prophets. PMID- 26542995 TI - Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light? AB - Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light. PMID- 26542996 TI - Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats. AB - The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin. Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18 h after ibotenate injection. We determined lesion size at 5 days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR. Dextran extravasation was seen 2h after the insult, suggesting a rapid BBB breakdown that was resolved by 4h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin. Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects. PMID- 26542997 TI - The role of intramolecular self-destruction of reactive metabolic intermediates in determining toxicity. AB - When reactive centers are formed in chemical conversions, intermolecular reactions tend to dominate over intramolecular alternatives whenever both alternatives are possible. Hence, when reactive metabolites are formed from xenobiotics, intramolecular quenching by moieties adjacent to a toxicophore may play an important role in reducing toxicity related to reactive intermediates. The phenomenon is likely to be particularly noticeable for toxicophores that are readily associated with a type of toxicity that is rarely caused by other structural motives. In two demonstrative investigations, it is concluded that nitrobenzenes for which the expected nitrosyl metabolite is likely to react with adjacent groups are less toxic than what is rationally expected, and that among aryl amine drugs allowing for the immediate quenching of the corresponding N-aryl hydroxylamine metabolite, the typical erythrocyte toxicity often seen with aryl amines is absent. The deliberate introduction of effective quenching groups nearby a toxicophoric moiety may present a potential strategy for reducing toxicity in the design of drugs and other man-made xenobiotics. PMID- 26542998 TI - Calcified nodules on fingers in primary hyperoxaluria type 2. PMID- 26542999 TI - When should we change our clinical practice based on the results of a clinical study? Diagnostic accuracy studies I: the study design. PMID- 26543000 TI - Lesser saphenous vein thrombosis diagnosed by point-of-care ultrasound in a patient presenting with pulmonary embolism. PMID- 26543001 TI - Ultrasound-guided drainage of peritonsillar abscess: shoot with your hockey stick. PMID- 26543002 TI - Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry. AB - The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume ( 16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp(+/-) and cbp(+/+) littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders. PMID- 26543003 TI - Complementing Graphenes: 1D Interplanar Charge Transport in Polymeric Graphitic Carbon Nitrides. AB - Charge transport in polymeric graphitic carbon nitrides is shown to proceed via diffusive hopping of electron and hole polarons with reasonably high mobilities >10(-5) cm(2) V(-1) s(-1). The power-law behavior of the ultrafast luminescence decay exhibits that the predominant transport direction is perpendicular to the graphitic polymer sheets, thus complementing 2D materials like graphene. PMID- 26543005 TI - Role of Laser Doppler for the Evaluation of Pedal Microcirculatory Function in Diabetic Neuropathy Patients. AB - OBJECTIVE: We evaluated whether LD can detect alterations in skin microcirculatory flow in type II diabetic neuropathy patients and determined which parameters were most predictive. METHODS: A prospective analysis was performed for three groups with presumed varying degrees of microvascular dysfunction: diabetics with neuropathy (DMN, n = 20), diabetics without microangiopathic complications (DM, n = 20), and healthy controls (n = 16). LD was performed under strictly controlled protocols with provocation, consisting of vasoconstrictive (valsalva, postural) and vasodilative tests (PORH, LTH). RESULTS: There was an overall decrease in LD values in response to both vasoconstrictive and vasodilative provocations in DMN patients compared to DM and control groups. Statistically significant parameters were as follows: valsalva, PORH and LTH between DMN and control; valsalva only between DMN and DM; and PORH and LTH between DM and control. ROC curve analysis showed that Valsalva was the most accurate parameter in DMN patients. CONCLUSIONS: LD could consistently detect differences in microcirculatory flow between the three study groups consisting of gradually more severe microvascular dysfunction. The Valsalva parameter was the most accurate in detecting established microvascular dysfunction, whereas PORH and LTH may have a possible role for detection of early microvascular impairment. PMID- 26543004 TI - Intrinsic Visual-Motor Synchrony Correlates With Social Deficits in Autism. AB - BACKGROUND: Imitation, which is impaired in children with autism spectrum disorder (ASD) and critically depends on the integration of visual input with motor output, likely impacts both motor and social skill acquisition in children with ASD; however, it is unclear what brain mechanisms contribute to this impairment. Children with ASD also exhibit what appears to be an ASD-specific bias against using visual feedback during motor learning. Does the temporal congruity of intrinsic activity, or functional connectivity, between motor and visual brain regions contribute to ASD-associated deficits in imitation, motor, and social skills? METHODS: We acquired resting-state functional magnetic resonance imaging scans from 100 8- to 12-year-old children (50 ASD). Group independent component analysis was used to estimate functional connectivity between visual and motor systems. Brain-behavior relationships were assessed by regressing functional connectivity measures with social deficit severity, imitation, and gesture performance scores. RESULTS: We observed increased intrinsic asynchrony between visual and motor systems in children with ASD and replicated this finding in an independent sample from the Autism Brain Imaging Data Exchange. Moreover, children with more out-of-sync intrinsic visual-motor activity displayed more severe autistic traits, while children with greater intrinsic visual-motor synchrony were better imitators. CONCLUSIONS: Our twice replicated findings confirm that visual-motor functional connectivity is disrupted in ASD. Furthermore, the observed temporal incongruity between visual and motor systems, which may reflect diminished integration of visual consequences with motor output, was predictive of the severity of social deficits and may contribute to impaired social-communicative skill development in children with ASD. PMID- 26543006 TI - Clinical Update on Nursing Home Medicine: 2015. AB - This is the ninth yearly update on clinical care in the nursing home. Topics covered this year are disease management in frail elders, heart failure, pneumonia, mild cognitive impairment, meaningful activities in the nursing home, atrial fibrillation, and anticoagulation. PMID- 26543007 TI - The Effect of an Online Cognitive Training Package in Healthy Older Adults: An Online Randomized Controlled Trial. AB - INTRODUCTION: Cognitive training (CT) offers a potential approach for dementia prevention and maintenance of cognitive function in older adults. Online delivery provides a cost-effective means of implementing CT compared with in-person interventions, with the potential of providing an effective public health intervention for risk reduction. METHODS: A double-blind 6-month online randomized controlled trial in adults older than 50 randomized to General CT, Reasoning CT, or control. The primary outcome was instrumental activities of daily living (IADL) in adults older than 60. Secondary outcomes were reasoning, verbal short-term memory, spatial working memory, verbal learning (VL), and digit vigilance in adults older than 50. Secondary analyses were performed with a group defined as showing age-associated impairment in reasoning according to baseline scores in this domain. RESULTS: A total of 2912 adults older than 60 (6742 > 50) participated. General and reasoning packages conferred benefit to IADL (P = .008, P = .011), reasoning (P < 0.0001, P < .0001), and VL (P = .007, P = .008) at 6 months. Benefit in reasoning was evident from 6 weeks. Other benefits developed over 6 months. Analysis of participants with age-associated impairment also showed the same pattern of benefit. A clear dose-response effect was seen. CONCLUSIONS: Online CT confers significant benefit to cognition and function in older adults, with benefit favoring the Reasoning package. Scale of benefit is comparable with in-person training, indicating its potential as a public health intervention. Impact on the group with age-associated impairment indicates a particular sensitivity to this at-risk group, which merits further investigation. PMID- 26543010 TI - Effectiveness of patient navigator interventions on uptake of colorectal cancer screening in primary care settings. AB - AIM: Colorectal cancer is the fourth most common type of cancer in the world and every year it is responsible for 610,000 deaths worldwide. The aim of this review was to examine the effectiveness of patient navigator interventions towards enhancing uptake of colorectal cancer screening in primary care settings. METHODS: Electronic databases such as PubMed, CINHAL, Google Scholar and SCOPUS were searched to retrieve articles reporting on primary studies applying any patient navigator intervention to promote uptake of colorectal cancer screening in eligible patients. The search yielded 292 articles and 15 met the inclusion criteria. RESULTS: All 15 studies were conducted in urban settings located in the USA. The findings of the review show that patient navigator interventions can increase colorectal cancer screening rates in diverse primary care settings. Patient navigator interventions were most effective in patients who belong to minority groups and enhanced uptake of colorectal cancer screening with rates ranging 11-91%. CONCLUSION: There is a need for further studies to examine the effectiveness of patient navigator interventions in rural populations and other countries. Such studies will help us to clearly characterize the effectiveness of patient navigator interventions. PMID- 26543008 TI - The Case for Stage-Specific Frailty Interventions Spanning Community Aging to Cognitive Impairment. AB - OBJECTIVES: To explore factors associated with frailty across the continuum of healthy aging to cognitive impairment (mild cognitive impairment [MCI], mild and moderate Alzheimer disease [AD]). DESIGN: Cross-sectional study. SETTING: Senior activity centers and the outpatient memory clinic of a tertiary hospital. PARTICIPANTS: Community-dwelling and functionally independent adults aged 50 years and older and older adults attending the memory clinic with MCI, and mild and moderate AD diagnoses. METHODS: We recruited 299 participants comprising 200 cognitively healthy individuals, 16 with MCI, 68 with mild AD, and 15 with moderate AD. We collected measures of comorbidities, cognitive and functional performance, physical activity level, and anthropometric and nutritional status. Frailty was defined using Buchmann criteria, and sarcopenic obesity (SO) was defined using the Asian Working Group for Sarcopenia criteria and the revised National Cholesterol and Education Panel-obesity definition of waist circumference. Multiple logistic regression was performed to identify factors associated with frailty as a whole group and separately based on cognitive subgroups. RESULTS: There were 16.7% of patients who met frailty criteria. Frailty prevalence was lowest in the well elderly (3.5%) and subsequently followed a U-shaped prevalence from MCI to mild and moderate AD, respectively. Specific univariate differences were noted in age, hypertension, ischemic heart disease, depressive symptoms, social differences, and functional scores. Multivariable logistic regression showed age, cognitive status, and SO to be significantly associated with frailty status. Subgroup analysis showed only SO to be significant (odds ratio [OR] 15.55, 95% confidence interval [CI] 1.63-148.42) in well elderly and only cognition to be associated with frailty (OR 0.89, 95% CI 0.80-0.99) among the cognitively impaired. CONCLUSION: Our findings lend initial support to the case for stage-specific interventions for physical frailty with the focus on SO in healthy community-dwelling older persons and cognitive-based measures in older adults with cognitive impairment. The accurate clinical phenotyping would then set the stage for future potential investigative therapies along these specific lines, rather than an undifferentiated approach. PMID- 26543011 TI - Micro-metric electronic patterning of a topological band structure using a photon beam. AB - In an ideal 3D topological insulator (TI), the bulk is insulating and the surface conducting due to the existence of metallic states that are localized on the surface; these are the topological surface states. Quaternary Bi-based compounds of Bi(2-x)Sb(x)Te(3-y)Se(y) with finely-tuned bulk stoichiometries are good candidates for realizing ideal 3D TI behavior due to their bulk insulating character. However, despite its insulating bulk in transport experiments, the surface region of Bi(2-x)Sb(x)Te(3-y)Se(y) crystals cleaved in ultrahigh vacuum also exhibits occupied states originating from the bulk conduction band. This is due to adsorbate-induced downward band-bending, a phenomenon known from other Bi based 3D TIs. Here we show, using angle-resolved photoemission, how an EUV light beam of moderate flux can be used to exclude these topologically trivial states from the Fermi level of Bi1.46Sb0.54Te1.7Se1.3 single crystals, thereby re establishing the purely topological character of the low lying electronic states of the system. We furthermore prove that this process is highly local in nature in this bulk-insulating TI, and are thus able to imprint structures in the spatial energy landscape at the surface. We illustrate this by 'writing' micron sized letters in the Dirac point energy of the system. PMID- 26543012 TI - Cytoskeletal signaling in TGFbeta-induced epithelial-mesenchymal transition. AB - Epithelial-mesenchymal transition (EMT) is a physiological process that plays an important role in embryonic development and wound healing and is appropriated during pathological conditions including fibrosis and cancer metastasis. EMT can be initiated by a variety of factors, including transforming growth factor (TGF) beta, and is characterized by loss of epithelial features including cell-cell contacts and apicobasal polarity and acquisition of a motile, mesenchymal phenotype. A key feature of EMT is reorganization of the cytoskeleton and recent studies have elucidated regulation mechanisms governing this process. This review describes changes in gene expression patterns of cytoskeletal associated proteins during TGFbeta-induced EMT. It further reports TGFbeta-induced intracellular signaling cascades that regulate cytoskeletal reorganization during EMT. Finally, it highlights how changes in cytoskeletal architecture during EMT can regulate gene expression, thus further promoting EMT progression. PMID- 26543013 TI - Nocturnal indicators of increased cardiovascular risk in depressed adolescent girls. AB - Depression is an independent risk factor for cardiovascular disease in adults, and recent literature suggests preclinical signs of cardiovascular risk are also present in depressed adolescents. No study has examined the effect of clinical depression on cardiovascular factors during sleep. This study examined the relationship between clinical depression and nocturnal indicators of cardiovascular risk in depressed adolescent girls from the general community (13 18 years old; 11 clinically depressed, eight healthy control). Continuous beat-to beat finger arterial blood pressure and heart rate were monitored via Portapres and electrocardiogram, respectively. Cardiovascular data were averaged over each hour for the first 6 h of sleep, as well as in 2-min epochs of stable sleep that were then averaged within sleep stages. Data were also averaged across 2-min epochs of pre-sleep wakefulness and the first 5 min of continuous non-rapid eye movement sleep to investigate the blood pressure dipping response over the sleep onset period. Compared with controls, depressed adolescents displayed a similar but significantly elevated blood pressure profile across sleep. Depressed adolescents had significantly higher systolic and diastolic blood pressure and mean arterial pressures across the entire night (P < 0.01), as well as during all sleep stages (P < 0.001). Depressed adolescents also had higher blood pressure across the sleep-onset period, but the groups did not differ in the rate of decline across the period. Higher blood pressure during sleep in depressed adolescent females suggests that depression has a significant association with cardiovascular functioning during sleep in adolescent females, which may increase risk for future cardiovascular pathology. PMID- 26543014 TI - Corrigendum: Plasticity of Listeriolysin O Pores and its Regulation by pH and Unique Histidine. PMID- 26543016 TI - Removing the Active-Site Flap in Lipase A from Candida antarctica Produces a Functional Enzyme without Interfacial Activation. AB - A mobile region is proposed to be a flap that covers the active site of Candida antarctica lipase A. Removal of the mobile region retains the functional properties of the enzyme. Interestingly interfacial activation, required for the wild-type enzyme, was not observed for the truncated variant, although stability, activity, and stereoselectivity were very similar for the wild-type and variant enzymes. The variant followed classical Michaelis-Menten kinetics, unlike the wild type. Both gave the same relative specificity in the transacylation of a primary and a secondary alcohol in organic solvent. Furthermore, both showed the same enantioselectivity in transacylation of alcohols and the hydrolysis of alcohol esters, as well as in the hydrolysis of esters chiral at the acid part. PMID- 26543015 TI - Spousal Caregivers of Coronary Artery Bypass Surgery Patients: Differences between Caregivers with Low vs. High Caregiving Demands. AB - PURPOSE: Compared to non-caregivers, caregivers have higher rates of depressive symptoms, caregiver strain, less mutuality, and health care visits. However, few investigators have examined family caregivers after coronary artery bypass (CAB) surgery. The purpose of this study was to examine differences in caregiving difficulties, mutuality (i.e., open communication; avoiding sad thoughts), and depressive symptoms based on low vs. high caregiving demands among spousal caregivers. DESIGN: A descriptive, comparative design was used to examine 33 spousal caregivers of CAB surgery patients (16 in low and 17 in high caregiving demand groups). METHODS: Measures included: Caregiving Burden Scale, Mutuality and Interpersonal Sensitivity Scale, and Patient Health Questionnaire-9. Groups were compared using Mann-Whitney U statistics. FINDINGS: It was found that caregivers with high caregiving demands reported more caregiving difficulties and more open communication about the surgery compared to caregivers with low demands. CONCLUSION: Caregivers with greater caregiving demands may need additional support to assist them with the caregiving situation. CLINICAL RELEVANCE: Priority should be given to family caregivers, who take care of patients in cardiac rehabilitation, with higher caregiving demand. PMID- 26543017 TI - Arterial Stiffness, Central Pulsatile Hemodynamic Load, and Orthostatic Hypotension. AB - The association between central pulsatile hemodynamic load, arterial stiffness, and orthostatic hypotension (OH) is unclear. The authors recruited 1099 participants from the community. Questionnaire, physical examination, and laboratory tests were performed. To assess the correlation between central pulsatile hemodynamic load, arterial stiffness, and OH, multiple logistic regression analysis was performed, and the discriminatory power was assessed by the area under the receiver operating curve. The prevalence of OH in this population was 5.6%. After adjusting for potential confounders, brachial-ankle pulse wave velocity (BaPWV) was significantly and positively correlated with OH in both the hypertension and nonhypertension groups (all P<.05), while central systolic blood pressure (CSBP) was only significantly associated with OH in the hypertension subgroup. In addition, BaPWV seemed to have a better discriminatory power than CSBP in both subgroups. BaPWV appears to be a better indicator of OH than CSBP in routine clinical practice. PMID- 26543019 TI - Long-Term Post-CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions. AB - BACKGROUND/AIM: Clinical risk models are commonly used to predict short-term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long-term mortality. The added value of long-term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long-term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. METHODS: Long-term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c-index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. RESULTS: Mortality rates were 3%, 9%, and 17% at one-, three-, and five years, respectively (median follow-up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long-term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. CONCLUSIONS: Long-term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long-term mortality risk can be accurately assessed and subgroups of higher-risk patients can be identified for enhanced follow-up care. More research appears warranted to refine long-term CABG clinical risk models. PMID- 26543018 TI - The effect of vitamin D supplementation on insulin and glucose metabolism in overweight and obese individuals: systematic review with meta-analysis. AB - The aim of this systematic review was to assess the effect of vitamin D supplementation on glucose and insulin metabolism in overweight and obese subjects. The search process was based on the selection of publications listed in the databases: PubMed, Scopus, Web of Knowledge, Embase and the Cochrane library that met the inclusion criteria. Twelve randomized controlled trials were included. The analysed population consisted of 1181 individuals with BMIs > 23 kg/m2. Changes in the concentration of 25(OH)D, fasting glucose, insulin and the HOMA-IR index were assessed. In the meta-regression analysis, a restricted maximum likelihood method was applied. To combine individual study results, a meta-analysis was performed. Vitamin D supplementation did not have an effect on glucose concentrations, insulin level and HOMA-IR values when the supplemented dose, time of supplementation and baseline of 25(OH)D concentration were taken under consideration in subgroup-analysis. This meta-analysis provides evidence that vitamin D supplementation has no significant effect on glucose and insulin metabolism in overweight and obese individuals. PMID- 26543020 TI - Biomineralization and biocompatibility studies of bone conductive scaffolds containing poly(3,4-ethylenedioxythiophene):poly(4-styrene sulfonate) (PEDOT:PSS). AB - Considering the well-known phenomenon of enhancing bone healing by applying electromagnetic stimulation, manufacturing conductive bone scaffolds is on demand to facilitate the delivery of electromagnetic stimulation to the injured region, which in turn significantly expedites the healing procedure in tissue engineering methods. For this purpose, hybrid conductive scaffolds composed of poly(3,4 ethylenedioxythiophene), poly(4-styrene sulfonate) ( PEDOT: PSS), gelatin (Gel), and bioactive glass (BaG) were produced employing freeze drying technique. Concentration of PEDOT: PSS were optimized to design the most appropriate conductive scaffold in terms of biocompatibility and cell proliferation. More specifically, scaffolds with four different compositions of 0, 0.1, 0.3 and 0.6% (w/w) PEDOT: PSS in the mixture of 10% (w/v) Gel and 30% (w/v) BaG were synthesized. Immersing the scaffolds in simulated body fluid (SBF), we evaluated the bioactivity of samples, and the biomineralization were studied in details using scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction analysis and Fourier transform infrared spectroscopy. By performing cytocompatibility analyses for 21 days using adult human mesenchymal stem cells, we concluded that the scaffolds with 0.3% (w/w) PEDOT: PSS and conductivity of 170 MUS/m has the optimized composition and further increasing the PEDOT: PSS content has inverse effect on cell proliferation. Based on our finding, addition of this optimized amount of PEDOT: PSS to our composition can increase the cell viability more than 4 times compared to a nonconductive composition. PMID- 26543021 TI - Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells. AB - The aim of this study was the preparation of novel polyester nanoparticles based on folic acid (FA)-functionalized poly(ethylene glycol)-poly(propylene succinate) (PEG-PPSu) copolymer and loaded with the new anticancer drug ixabepilone (IXA). These nanoparticles may serve as a more selective (targeted) treatment of breast cancer tumors overexpressing the folate receptor. The synthesized materials were characterized by (1)H-NMR, FTIR, XRD and DSC. The nanoparticles were prepared by a double emulsification and solvent evaporation method and characterized with regard to their morphology by scanning electron microscopy, drug loading with HPLC-UV and size by dynamic light scattering. An average size of 195 nm and satisfactory drug loading efficiency (3.5%) were observed. XRD data indicated that IXA was incorporated into nanoparticles in amorphous form. The nanoparticles exhibited sustained drug release properties in vitro. Based on in vitro cytotoxicity studies, the blank FA-PEG-PPSu nanoparticles were found to be non toxic to the cells. Fluorescent nanoparticles were prepared by conjugating Rhodanine B to PEG-PPSu, and live cell, fluorescence, confocal microscopy was applied in order to demonstrate the ability of FA-PEG-PPSu nanoparticles to enter into human breast cancer cells expressing the folate receptor. PMID- 26543022 TI - Macrophage-mediated osteogenesis activation in co-culture with osteoblast on calcium silicate cement. AB - The use of calcium silicate (CS) cement holds great promise for bone substitute biomaterials. However, the effects of CS on osteoblast and macrophage cells are not fully understood. This study examines cell proliferation and differentiation of mono- or co-cultured MC3T3-E1 and Raw 264.7 cells on CS cement. Very few studies to date have looked at the effects of osteoblast and macrophages on biomaterial-regulated osteogenesis. In this study the proliferation and differentiation of MC3T3-E1, Raw 264.7 and co-cultured MC3T3-E1/Raw 264.7 on CS cements have been analyzed using a PrestoBlue kit and ELISA. In addition, the effect of macrophages on CS-coordinated osteogenesis of MC3T3-E1 has been investigated. Results show that MC3T3-E1, Raw 264.7 and co-cultured MC3T3-E1/Raw 264.7 adhere to and proliferate well on the CS cement. In a co-culture, the CS cements inhibit receptor activator of nuclear factor kappa B ligand expression of both genes and proteins in Raw 264.7 cells when compared to those grown in mono cultured system. Ca deposition of MC3T3-E1 in the co-culture is higher than that of cells in a mono-culture. Bone morphogenetic protein 2 (BMP2) is also significantly up-regulated by the CS cement stimulation, indicating that macrophages may participate in the CS stimulated osteogenesis. Interestingly, when macrophage are cultured with BMP2 receptor-blocking MC3T3-E1 on the CS cements, the osteogenesis differentiation of the cells is significantly inhibited, indicating the important role of macrophages in biomaterial-induced osteogenesis via BMP2 receptors. It is assumed that it is an increase in the secretion of the BMP2 from the Raw 264.7 cell that is primarily involved in the promotion of the osteogenesis of the MC3T3-E1. These results provide valuable insights into both the mechanism of CS-stimulated osteogenesis, and strategies to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute biomaterials. PMID- 26543023 TI - Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks. AB - Inhibiting responses is a challenge, where the outcome (partly) depends on the situational context. In everyday situations, response inhibition performance might be altered when irrelevant input is presented simultaneously with the information relevant for response inhibition. More specifically, irrelevant concurrent information may either brace or interfere with response-relevant information, depending on whether these inputs are redundant or conflicting. The aim of this study is to investigate neurophysiological mechanisms and the network underlying such modulations using EEG beamforming as method. The results show that in comparison to a baseline condition without concurrent information, response inhibition performance can be aggravated or facilitated by manipulating the extent of conflict via concurrent input. This depends on whether the requirement for cognitive control is high, as in conflicting trials, or whether it is low, as in redundant trials. In line with this, the total theta frequency power decreases in a right hemispheric orbitofrontal response inhibition network including the SFG, MFG, and SMA, when concurrent redundant information facilitates response inhibition processes. Vice versa, theta activity in a left hemispheric response inhibition network (i.e., SFG, MFG, and IFG) increases, when conflicting concurrent information compromises response inhibition processes. We conclude that concurrent information bi-directionally shifts response inhibition performance and modulates the network architecture underlying theta oscillations which are signaling different levels of the need for cognitive control. PMID- 26543024 TI - Upregulation of S1P1 and Rac1 receptors in the pulmonary vasculature of nitrofen induced congenital diaphragmatic hernia. AB - PURPOSE: Sphingolipids play a crucial role in pulmonary development. The sphingosine kinase 1 (SphK1) modulates the synthesis of sphingolipid sphingosine 1-phosphate (S1P). S1P regulates cell proliferation and angiogenesis via different receptors, S1P1, S1P2 and S1P3, which all influence the expression of Ras-related C3 botulinum toxin substrate 1 (Rac1). We designed this study to test the hypothesis that the S1P/Rac1 pathway is altered in the nitrofen-induced CDH model. METHODS: Pregnant rats received nitrofen or vehicle on D9. On D21, fetuses were killed and divided into nitrofen and control group (n = 12). QRT-PCR, western blotting and confocal-immunofluorescence microscopy were performed to reveal pulmonary gene and protein expression levels of SphK1, S1P1, S1P2, S1P3 and Rac1. RESULTS: Pulmonary gene expression of S1P1 and Rac1 was significantly increased in the CDH group compared to controls, whereas S1P2 and S1P3 expression was decreased. These results were confirmed by western blotting and confocal microscopy. SphK1 expression was not found to be altered. CONCLUSION: The increased expression of S1P1 and Rac1 in the pulmonary vasculature of nitrofen induced CDH lungs suggests that S1P1 and Rac1 are important mediators of PH in this model. PMID- 26543025 TI - Accidental overdose in the deep shade of night: a warning on the assumed safety of 'natural substances'. AB - There is an increasing use of herbal remedies and medicines, with a commonly held belief that natural substances are safe. We present the case of a 50-year-old woman who was a trained herbalist and had purchased an 'Atropa belladonna (deadly nightshade) preparation'. Attempting to combat her insomnia, late one evening she deliberately ingested a small portion of this, approximately 50 mL. Unintentionally, this was equivalent to a very large (15 mg) dose of atropine and she presented in an acute anticholinergic syndrome (confused, tachycardic and hypertensive) to our accident and emergency department. She received supportive management in our intensive treatment unit including mechanical ventilation. Fortunately, there were no long-term sequelae from this episode. However, this dramatic clinical presentation does highlight the potential dangers posed by herbal remedies. Furthermore, this case provides clinicians with an important insight into potentially dangerous products available legally within the UK. To help clinicians' understanding of this our discussion explains the manufacture and 'dosing' of the A. belladonna preparation. PMID- 26543026 TI - A novel splicing mutation in the albumin gene (c.270+1G>T) causes analbuminaemia in a German infant. AB - Congenital analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital analbuminaemia. PMID- 26543028 TI - Quantifying and correcting for tail vein extravasation in small animal PET scans in cancer research: is there an impact on therapy assessment? AB - BACKGROUND: Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment. METHODS: In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification. RESULTS: Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (rho c = 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and 1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05). CONCLUSIONS: Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur. PMID- 26543027 TI - Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice. AB - The beta-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the beta-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the beta-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine's reinforcing efficacy at 100-fold lower doses than CTX. PMID- 26543030 TI - Germany considers legalising cannabis for medical use. PMID- 26543029 TI - Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation. AB - PURPOSE: The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques. PROCEDURES: The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations. RESULTS: The complete process led, in 50 min, to pure Ga-68 products in a 12-38 % yield and with appreciable specific radioactivity (SRA, 85-168 GBq/MUmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood-brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography. CONCLUSION: Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers. PMID- 26543032 TI - Tibial Bone Strength is Enhanced in the Jump Leg of Collegiate-Level Jumping Athletes: A Within-Subject Controlled Cross-Sectional Study. AB - An efficient method of studying skeletal adaptation to mechanical loading is to assess side-to-side differences (i.e., asymmetry) within individuals who unilaterally exercise one side of the body. Within-subject controlled study designs have been used to explore skeletal mechanoadaptation at upper extremity sites; however, there is no established model in the lower extremities. The current study assessed tibial diaphysis and distal tibia asymmetry in collegiate level jumping athletes (N = 12). To account for normal crossed asymmetry, data in jumping athletes were compared to asymmetry in a cohort of athletic controls not routinely exposed to elevated unilateral lower extremity loading (N = 11). Jumpers exhibited side-to-side differences between their jump and lead legs at both the tibial diaphysis and distal tibia, with differences at the former site persisting following comparison to dominant-to-nondominant leg differences in controls. In particular, jump-to-lead leg differences for cortical area and thickness at the tibial diaphysis in jumpers were 3.6% (95% CI 0.5-6.8%) and 3.5% (95% CI 0.4-6.6%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Similarly, jump-to-lead leg differences in jumpers for tibial diaphysis maximum second moment of area and polar moment of inertia were 7.2% (95% CI 1.2-13.2%) and 5.7% (95% CI 1.7-9.8%) greater than dominant-to nondominant differences in controls, respectively (all p < 0.05). Assessment of region-specific differences of the tibial diaphysis in jumpers indicated that the jump leg had greater pericortical radii on the medial and posterior sides and greater radial cortical thickness posteromedially when compared to the lead leg. These data suggest that athletes who perform repetitive and forceful unilateral jumping may be a useful and efficient within-subject controlled model for studying lower extremity skeletal mechanoadaptation. PMID- 26543033 TI - Systemic Treatment with Strontium Ranelate Does Not Influence the Healing of Femoral Mid-shaft Defects in Rats. AB - Strontium ranelate (SrR) has both bone anabolic and anti-resorption properties and has therefore the potential to increase the healing of bone defects. The aim of the present study was to investigate the effect of systemic treatment with SrR during the healing of cortical bone defects in rats. In addition, the vertebral bodies were examined in order to elucidate the effect of short-term treatment with SrR on intact trabecular bone. Sixty 16-week-old female Wistar rats were randomized into four groups. A cylindrical defect was drilled through the anterior cortex of the mid-femoral diaphysis in both hind limbs. Two of the groups were treated with SrR (900 mg/kg b.w.) mixed into the food and two groups served as controls. The animals were euthanized after either 3 or 8 weeks of treatment. Healing of the defects was analyzed with uCT, mechanical testing, and stereology. Treatment with SrR resulted in increased thickness of the defects after 3 weeks of treatment, whereas no effect on bone volume fraction (BV/TV), mechanical properties (maximum strength and maximum stiffness), periosteal callus volume, or osteoclast-covered bone surfaces (Oc.S/BS) after either 3 or 8 weeks of treatment was found. Furthermore, SrR increased the bone material density (rho) of the vertebral bodies, and tended to increase BV/TV after 8 weeks of treatment (p = 0.087). The mechanical properties of the vertebral bodies were not influenced by SrR treatment. In conclusion, 3 weeks of treatment with SrR increased the thickness of the healing mid-femoral cortical bone defects in rats, but did not influence BV/TV, mechanical properties, periosteal callus volume, or Oc.S/BS after either 3 or 8 weeks. Furthermore, SrR had no effect on the microstructure and mechanical properties of the vertebral bodies. PMID- 26543034 TI - Conservative management of midcarpal instability. AB - Midcarpal instability is a complex condition that can present in various forms, from mild pain to debilitating subluxation. Once diagnosed, treatment guidelines for hand therapy are limited by the scarcity of high-level evidence. Evidence does exist for use of proprioceptive awareness and neuromuscular rehabilitation for instability of the knee, shoulder and ankle joint, but studies of similar programmes for the wrist joint have not been published. The purpose of this review is to examine the evidence supporting current concepts in the non operative management of midcarpal instability, and to provide recommendations for the management of this condition with hand therapy. PMID- 26543031 TI - Review: can diet influence the selective advantage of mitochondrial DNA haplotypes? AB - This review explores the potential for changes in dietary macronutrients to differentially influence mitochondrial bioenergetics and thereby the frequency of mtDNA haplotypes in natural populations. Such dietary modification may be seasonal or result from biogeographic or demographic shifts. Mechanistically, mtDNA haplotypes may influence the activity of the electron transport system (ETS), retrograde signalling to the nuclear genome and affect epigenetic modifications. Thus, differential provisioning by macronutrients may lead to selection through changes in the levels of ATP production, modulation of metabolites (including AMP, reactive oxygen species (ROS) and the NAD(+)/NADH ratio) and potentially complex epigenetic effects. The exquisite complexity of dietary influence on haplotype frequency is further illustrated by the fact that macronutrients may differentially influence the selective advantage of specific mutations in different life-history stages. In Drosophila, complex I mutations may affect larval growth because dietary nutrients are fed through this complex in immaturity. In contrast, the majority of electrons are provided to complex III in adult flies. We conclude the review with a case study that considers specific interactions between diet and complex I of the ETS. Complex I is the first enzyme of the mitochondrial ETS and co-ordinates in the oxidation of NADH and transfer of electrons to ubiquinone. Although the supposition that mtDNA variants may be selected upon by dietary macronutrients could be intuitively consistent to some and counter intuitive to others, it must face a multitude of scientific hurdles before it can be recognized. PMID- 26543035 TI - Characterization of a novel Acinetobacter baumannii xanthine dehydrogenase expressed in Escherichia coli. AB - OBJECTIVE: To characterize a novel xanthine dehydrogenase (XDH) from Acinetobacter baumannii by recombinant expression in Escherichia coli and to assess its potential for industrial applications. RESULTS: The XDH gene cluster was cloned from A. baumannii CICC 10254, expressed heterologously in E. coli and purified to homogeneity. The purified recombinant XDH consisted of two subunits with the respective molecular weights of 87 kDa and 56 kDa according to SDS-PAGE. XDH catalysis was optimum at pH 8.5 and 40-45 degrees C, was stable under alkaline conditions (pH 7-11) and the half-inactivation temperature was 60 degrees C. The K m, turnover number and catalytic efficiency for xanthine were 25 MUM, 69 s(-1) and 2.7 MUM(-1) s(-1), respectively, which is an improvement over XDHs characterized previously. A. baumannii XDH is less than 50 % identical to previously identified XDH orthologs from other species, and is the first from the Acinetobacter genus to be characterized. CONCLUSION: The novel A. baumannii enzyme was found to be among the most active, thermostable and alkaline-tolerant XDH enzymes reported to date and has potential for use in industrial applications. PMID- 26543037 TI - Enhancement of cellulose degradation in freshwater sediments by a sediment microbial fuel cell. AB - OBJECTIVE: To demonstrate that an enhanced sediment microbial fuel cell (SMFC) system can accelerate the degradation of cellulose in fresh water sediments as the accumulation of cellulose in lake sediments may aggravate the lake marsh, increase organic matter content and result in rapid deterioration of water quality and damage the ecosystem. RESULTS: After 330 days the highest cellulose removal efficiency (72.7 +/- 2.1 %) was achieved in the presence of a SMFC with a carbon nanotube decorated cathode, followed by a SMFC without the cathode decoration (64.4 +/- 2.8 %). The lowest cellulose removal efficiency (47.9 +/- 2.1 %) was in the absence of SMFC. The sediment characterization analysis confirmed that the carbon nanotube decorated cathode enhances the electron transfer rate in the SMFC and improves the dissolved organic matter oxidation rate. CONCLUSION: This study offers a relatively simple and promising new method for cellulose degradation in sediment. PMID- 26543036 TI - Catalase improves saccharification of lignocellulose by reducing lytic polysaccharide monooxygenase-associated enzyme inactivation. AB - OBJECTIVES: Efficient enzymatic saccharification of plant cell wall material is key to industrial processing of agricultural and forestry waste such as straw and wood chips into fuels and chemicals. RESULTS: Saccharification assays were performed on steam-pretreated wheat straw under ambient and O2-deprived environments and in the absence and presence of a lytic polysaccharide monooxygenase (LPMO) and catalase. A kinetic model was used to calculate catalytic rate and first-order inactivation rate constants of the cellulases from reaction progress curves. The addition of a LPMO significantly (P < 0.01, Student's T test) enhanced the rate of glucose release from 2.8 to 6.9 h(-1) under ambient O2 conditions. However, this also significantly (P < 0.01, Student's T test) increased the rate of inactivation of the enzyme mixture, thereby reducing the performance half-life from 65 to 35 h. Decreasing O2 levels or, strikingly, the addition of catalase significantly reduced (P < 0.01, Student's T test) enzyme inactivation and, as a consequence, higher efficiency of the cellulolytic enzyme cocktail was achieved. CONCLUSION: Oxidative inactivation of commercial cellulase mixtures is a significant factor influencing the overall saccharification efficiency and the addition of catalase can be used to protect these mixtures from inactivation. PMID- 26543038 TI - Relationship between morphological characteristics of hyoid bone and mandible in Japanese cadavers using three-dimensional computed tomography. AB - The aim of this study is to obtain a quantitative anatomical description of the hyoid bone and mandible using three-dimensional computed tomography. Hyoid bones were obtained from a total of 101 cadavers varying in age from 67 to 102 years. The percentage of symmetrical U-type and asymmetrical-type hyoid bones was low compared with symmetrical V type (14.9, 15.8, and 69.3 %, respectively), and no significant sex difference was observed. We found bilateral nonfusion in cadavers of advanced age at a rate of 22.7 % and bilateral complete fusion at a rate of 51.5 %. There were significant differences in metric variables (length and width) between males and females, but no significant differences in width among the different fusion types. There was no significant interaction effect of sex and degree of fusion. Strong significant associations were observed between size (length and width) of the hyoid bone and mandible in the nonfusion group, while the complete fusion group revealed a moderate correlation. We also investigated the hypothesis that the junction between the hyoid body and greater horn plays an important role in the movement of bones that have not yet ossified. However, no statistical difference was observed in the width between the two greater horns. The degree of fusion of the greater horn with the hyoid body may also affect relations of interdependencies between the hyoid bone and mandible, an important component to consider when assessing risk factors in the development of masticatory and swallowing function. PMID- 26543040 TI - Elected Officials Travel in Parallel Universes Regarding the Affordable Care Act. AB - This authoritative appraisal of the much debated U.S. Patient Protection and Affordable Care Act, often referred to as Obamacare, describes the controversy, support, and opposition from federal and state governments during the first 5.5 years since the law was passed. Its history, the impact on individual and community health status, the limitations of health reform, its accomplishments and deficiencies, and the impact of societal determinants on program implementation are presented in a refreshing, candid, objective, and knowledgeable manner. PMID- 26543039 TI - Dietary ALA from Spinach Enhances Liver n-3 Fatty Acid Content to Greater Extent than Linseed Oil in Mice Fed Equivalent Amounts of ALA. AB - Although several works have reported absorption rate differences of n-3 polyunsaturated fatty acids (PUFA) bound to different lipid forms, such as ethyl ester, triacylglycerol (TAG), and phospholipids, no studies have investigated the effect of n-3 PUFA from glycolipids (GL). The present study compared the fatty acid contents of tissue and serum lipids from normal C57BL/6J mice fed two types of alpha-linolenic acid (ALA)-rich lipids, spinach lipid (SPL), and linseed oil (LO). ALA was primarily present as the GL form in SPL, while it existed as TAG in LO. Supplementation of both lipids increased ALA and its n-3 metabolites, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid, and decreased n-6 PUFA, linoleic acid and arachidonic acid, in the livers, small intestines, and sera of the treated mice compared with those of the control group. When the comparison between the SPL and LO diets containing the same amount of ALA was conducted, the EPA and DPA levels in the liver lipids from mice fed the SPL diet were significantly higher than those fed the LO diet. Additionally, the total contents of n-3 PUFA of lipids from the livers, small intestines, and sera of the SPL group were higher than those of the LO group. PMID- 26543041 TI - Brain Activity and Network Interactions Linked to Valence-Related Differences in the Impact of Emotional Distraction. AB - Previous investigations showed that the impact of negative distraction on cognitive processing is linked to increased activation in a ventral affective system (VAS) and simultaneous deactivation in a dorsal executive system (DES). However, less is known about the influences of positive valence and different arousal levels on these effects. FMRI data were recorded while participants performed a working memory (WM) task, with positive and negative pictures presented as distracters during the delay between the memoranda and probes. First, positive distraction had reduced impact on WM performance, compared with negative distraction. Second, fMRI results identified valence-specific effects in DES regions and overlapping arousal and valence effects in VAS regions, suggesting increased impact of negative distraction and enhanced engagement of coping mechanisms for positive distraction. Third, a valence-related rostro caudal dissociation was identified in medial frontal regions associated with the default-mode network (DMN). Finally, these DMN regions showed increased functional connectivity with DES regions for negative compared with positive distraction. Overall, these findings suggest that, while both positive and negative distraction engage partly similar arousal-dependent mechanisms, their differential impact on WM performance is linked to dissociations in the engagement of, and coupling between, regions associated with emotion processing and higher lever cognitive control. PMID- 26543042 TI - Paediatrician found guilty of manslaughter after boy's death from septic shock. PMID- 26543043 TI - Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. AB - Western societies are aging due to an increasing life span, decreased birth rates, and improving social and health conditions. On the other hand, the prevalence of cardiovascular (CV) and cerebrovascular (CBV) diseases rises with age. Thus, in view of the ongoing aging pandemic, it is appropriate to better understand the molecular pathways of aging as well as age-associated CV and CBV diseases. Oxidative stress contributes to aging of organs and the whole body by an accumulation of reactive oxygen species promoting oxidative damage. Indeed, increased oxidative stress produced in the mitochondria and cytosol of heart and brain is a common denominator to almost all CV and CBV diseases. The mitochondrial adaptor protein p66(Shc) and the family of deacetylase enzymes, the sirtuins, regulate the aging process, determine lifespan of many species and are involved in CV diseases. GDF11, a member of TGFbeta superfamily with homology to myostatin also retards the aging process via yet unknown mechanisms. Recent evidence points towards a promising role of this novel 'rejuvenation' factor in reducing age-related heart disease. Finally, telomere length is also involved in aging and the development of age-related CV dysfunction. This review focuses on the latest scientific advances in understanding age-related changes of the CV and CBV system, as well as delineating potential novel therapeutic targets derived from aging research for CV and CBV diseases. PMID- 26543044 TI - Endovascular grafts for abdominal aortic aneurysm. AB - During the last two decades, endovascular technology has revolutionized the management of patients with abdominal aortic aneurysm (AAA). Today, endovascular aortic repair (EVAR) is the treatment of choice for the majority of patients with an AAA. Randomized controlled trials provide robust evidence for the indication of AAA repair and the rationale for the use of EVAR in selected patients. However, despite that, practice varies and several areas need further elucidation. Important future challenges and areas of research include the role of medical therapy in AAA, whether the indication for repair should be any different in women and in the elderly, and long-term follow-up of patients undergoing complex EVAR with adjuncts, both for elective treatment and for ruptured AAA. Continuous rapid technical and clinical development is to be expected. In this paper, we review the current practice and evidence of stenting in AAA. PMID- 26543045 TI - Left ventricular assist devices: current controversies and future directions. AB - Advanced heart failure is a growing epidemic that leads to significant suffering and economic losses. The development of left ventricular assist devices (LVADs) has led to improved quality of life and long-term survival for patients diagnosed with this devastating condition. This review briefly summarizes the short history and clinical outcomes of LVADs and focuses on the current controversies and issues facing LVAD therapy. Finally, the future directions for the role of LVADs in the treatment of end-stage heart failure are discussed. PMID- 26543046 TI - Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure. AB - Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure. PMID- 26543047 TI - Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. AB - Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients. PMID- 26543048 TI - Coronary evaginations and peri-scaffold aneurysms following implantation of bioresorbable scaffolds: incidence, outcome, and optical coherence tomography analysis of possible mechanisms. AB - BACKGROUND: Peri-stent coronary evaginations may disturb flow and have been proposed as possible risk factor for late stent thrombosis. We describe incidence, predictors, and possible mechanisms of coronary evaginations 12 months after implantation of bioresorbable vascular scaffolds (BVS). METHODS AND RESULTS: One hundred and two BVS implanted in 90 patients (age 63 +/- 13 years, 71 males, 14 diabetics) were analysed with angiography and optical coherence tomography (OCT) 12 months after implantation. Evaginations were identified as any hollow in the luminal vessel contour between well-apposed struts and were classified as major when extending >=3 mm with a depth >=10% of the BVS diameter. Fifty-five (54%) of the BVS (50(56%) of the patients) had at least one evagination (6.1 +/- 6.2 evaginations per BVS), with a mean volume of 1.9 +/- 1.9 mm(3). Major evaginations were only found in one patient, and in-BVS aneurysms in three patients (4BVS). The presence of evaginations was strongly associated with that of malapposition (P = 0.003) and strut fractures (P = 0.01). No association could be shown between the presence and volume of the evaginations and any clinical variable or the presence of uncovered struts (P > 0.5). Peri-strut low intensity areas (PSLIA) were present in 29 (53%) of the BVS with evaginations and 12 (26%) of those without (P = 0.0049); their presence was independently associated with the presence, the number (P < 0.003) and volume of the evaginations (P = 0.004) and with that of strut fracture. CONCLUSIONS: Optical coherence tomography-detected evaginations are relatively common after BVS implantation, but, as for modern drug-eluting metallic stents, major evaginations are very rare. Optical coherence tomography evidence of immature neointima and strut fractures were associated with more severe development of evaginations. PMID- 26543050 TI - Mike Richards: "sometimes people can trade too much on reputation". PMID- 26543049 TI - Modelling maternal obesity: the effects of a chronic high-fat, high-cholesterol diet on uterine expression of contractile-associated proteins and ex vivo contractile activity during labour in the rat. AB - Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present study investigated the effects of an adiposity-inducing high-fat, high-cholesterol (HFHC) diet on uterine contractile-associated protein (CAP) expression and ex vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n=20) or HFHC (n=20) diet 6 weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX 43) and it's phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P<=0.001), plasma cholesterol (P<=0.001) and triacylglycerol (P=0.039) concentrations. Stage of labour effected uterine expression of CAV-1 (P<0.02), pCX43 and COX-2 (both P<0.03). CAV-1 and pCX43 decreased but COX-2 increased with parturition. Significant diet- and labour-stage interactions were evident for CX-43 and pCX43 (P<0.03 and P<0.004 respectively). CX-43 decreased with TL in HFHC animals but was unaltered in CON. pCX-43 fell with labour in CON but remained high in HFHC. OXTR expression was significantly higher in HFHC compared with CON animals (P<0.03). Progesterone was higher in HFHC rats at term (P<0.014) but fell significantly with labour to similar concentrations as CON. Contractility studies identified synchronous contractions of stable amplitude in lean animals, but unstable asynchronous contractions with obesity. Uterine dose response to oxytocin was blunted during labour in HFHC rats with a log EC50 of -8.84 compared with -10.25 M in CON for integral activity (P<0.05). In conclusion, our adiposity model exhibits adverse effects on contractile activity during labour that can be investigated further to unravel the mechanisms causing uterine dystocia in obese women. PMID- 26543052 TI - Radiologic evaluation of portal steal phenomenon in recipients of liver transplantation. AB - It is important to maintain adequate portal flow and to prevent the detrimental effect of portosystemic shunt in recipients following liver transplantation. The purpose of this article is to present a comprehensive review of portosystemic shunts and to illustrate such phenomenon demonstrated on radiologic studies such as Doppler ultrasound, computed tomography, and portogram. It is important for radiologists to be aware of such phenomenon not only in preoperative evaluation of the recipients but also in postoperative screening to detect recurrence of the phenomenon. PMID- 26543051 TI - Diffusion-weighted magnetic resonance imaging in the differentiation of endometriomas from hemorrhagic cysts in the ovary. AB - BACKGROUND: The classic magnetic resonance imaging (MRI) feature of endometriomas is the shading sign, which is characterized by T2-shortening in ovarian cystic lesions that are hyperintense on T1-weighted images. The shading sign is infrequently observed in hemorrhagic ovarian cysts. PURPOSE: To investigate the value of MRI with diffusion-weighted imaging (DWI) for distinguishing endometriomas from hemorrhagic cysts in the ovary. MATERIAL AND METHODS: This retrospective study included 91 patients with 98 ovarian endometriomas and 21 hemorrhagic ovarian cysts that were confirmed pathologically, who had undergone MRI with DWI. Two radiologists compared MRI features, including size, bilaterality, multilocularity, the shading sign, the ovarian lesion/muscle signal intensity ratio at T2-weighted images, and T2 dark spots, between endometriomas and hemorrhagic cysts. We also compared the mean ADC value between endometriomas and hemorrhagic cysts, and determined the optimal cutoff ADC value for differentiating endometriomas from hemorrhagic cysts. RESULTS: The size and mean ADC values were significantly different between endometriomas and hemorrhagic cysts. The mean ADC values of endometriomas and hemorrhagic cysts were 1.06 +/- 0.38 * 10 (-3) mm(2)/s and 0.73 +/- 0.29 * 10(-3) mm(2)/s, respectively (P < 0.002). The optimal cutoff ADC value for differentiating endometriomas from hemorrhagic cysts was 0.849 * 10(-3) mm(2)/s (sensitivity, 77.6%; specificity, 76.2%). CONCLUSION: The addition of DWI could help in differentiating endometriomas from hemorrhagic cysts in the ovary, when conventional MRI is challenging. PMID- 26543053 TI - Radiologic evaluation of lumps in the male breast. AB - BACKGROUND: Gynecomastia has a typical appearance on mammography, and occurs frequently in men. However, imaging is often performed on men with breast lumps to exclude breast cancer, which only comprises 1% of male breast masses. PURPOSE: To assess whether ultrasound and fine needle aspiration cytology (FNAC) are necessary investigations when mammograms show classical gynecomastia. MATERIAL AND METHODS: We have retrospectively collected data on male patients referred for mammography during the period 2011-2013 (a total of 539 patients). All radiological images were re-read, and descriptions of ultrasound images were reviewed. Clinical information supplied with the original referrals was assessed, along with pathology and cytology reports. RESULTS: Among the 539 male patients who underwent mammography, 483 were also examined with ultrasound, and 335 were further evaluated with FNAC. Mammograms showed gynecomastia in 350 patients, and among these subjects ultrasound was performed in 340 (97%), FNAC in 261 (75%), and core biopsies in four (1%) patients. The diagnosis gynecomastia was unchanged in all patients who underwent FNAC or biopsy. Malignant tumors were found in eight patients, six of which were invasive ductal carcinomas. CONCLUSION: In patients with a classical appearance of gynecomastia on mammography, supplemental ultrasound, FNAC, or biopsy is superfluous and contributes to unnecessary costs. PMID- 26543055 TI - Honesty is needed on Scottish health service funding, says BMA. PMID- 26543054 TI - Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. AB - OBJECTIVE: Hereditary hypophosphatemias (HH) are rare monogenic conditions characterized by decreased renal tubular phosphate reabsorption. The aim of this study was to explore the prevalence, genotypes, phenotypic spectrum, treatment response, and complications of treatment in the Norwegian population of children with HH. DESIGN: Retrospective national cohort study. METHODS: Sanger sequencing and multiplex ligand-dependent probe amplification analysis of PHEX and Sanger sequencing of FGF23, DMP1, ENPP1KL, and FAM20C were performed to assess genotype in patients with HH with or without rickets in all pediatric hospital departments across Norway. Patients with hypercalcuria were screened for SLC34A3 mutations. In one family, exome sequencing was performed. Information from the patients' medical records was collected for the evaluation of phenotype. RESULTS: Twety eight patients with HH (18 females and ten males) from 19 different families were identified. X-linked dominant hypophosphatemic rickets (XLHR) was confirmed in 21 children from 13 families. The total number of inhabitants in Norway aged 18 or below by 1st January 2010 was 1,109,156, giving an XLHR prevalence of ~1 in 60,000 Norwegian children. FAM20C mutations were found in two brothers and SLC34A3 mutations in one patient. In XLHR, growth was compromised in spite of treatment with oral phosphate and active vitamin D compounds, with males tending to be more affected than females. Nephrocalcinosis tended to be slightly more common in patients starting treatment before 1 year of age, and was associated with higher average treatment doses of phosphate. However, none of these differences reached statistical significance. CONCLUSIONS: We present the first national cohort of HH in children. The prevalence of XLHR seems to be lower in Norwegian children than reported earlier. PMID- 26543056 TI - A body-sized phantom for evaluation of diffusion-weighted MRI data using conventional, readout-segmented, and zoomed echo-planar sequences. AB - BACKGROUND: Abdominal diffusion-weighted imaging (DWI) has been rapidly increasing during the last few years. For the evaluation of new DWI techniques, the development of suitable phantoms and quality assurance methods is important. PURPOSE: To construct a body-diameter phantom for abdominal DWI and study the impact of different acquisition options on image quality. MATERIAL AND METHODS: A phantom with a diameter of 31 cm and a volume of 26 L was constructed, containing four samples representing a clinically relevant range of apparent diffusion coefficient (ADC) values. Measurements were carried out on 1.5T and 3.0T MRI systems using conventional echo-planar imaging (EPI), readout-segmented EPI, and zoomed EPI (3.0T) sequences. The effects of parallel imaging, coil intensity normalization, and patient-specific B1 shim (3.0T) were also examined. ADC values and signal-to-noise ratios of the samples were measured, and the level of artifacts was visually evaluated. RESULTS: The agreement of ADC values between different acquisition options was generally good, but higher values (by 0.07 * 10(-3) mm(2)/s on the average) with readout-segmented EPI as well as ADC variations of approximately 0.1 * 10(-3) mm(2)/s in slice direction were observed. The image artifacts were reduced by using patient-specific B1 shim, readout-segmented EPI, or zoomed EPI. CONCLUSION: The body-sized phantom demonstrated well the expected image artifacts in DWI with large field of view. The use of patient-specific B1 shim, readout-segmented EPI, or zoomed EPI improved image quality of DWI in this study. PMID- 26543058 TI - Hunt's 11% pay rise offer to junior doctors fails to avert ballot on action. PMID- 26543057 TI - Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy. AB - Intra-arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first in-human, exploratory, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor-derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2-month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor-derived dystrophin in 1. Intra-arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy. PMID- 26543059 TI - Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women. AB - To assess whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with all-cause and disease-specific mortality in middle-aged women. METHODS: Four subgroups from the prospective community-based Chingford Cohort Study were identified based on presence/absence of pain and ROA at baseline: (Pain-/ROA-; Pain+/ROA-; Pain-/ROA+; Pain+/ROA+). Pain was defined as side-specific pain in the preceding month, while side-specific ROA was defined as Kellgren-Lawrence grade >=2. All-cause, cardiovascular disease (CVD) and cancer related mortality over the 23-year follow-up was based on information collected by the Office for National Statistics. Associations between subgroups and all cause/cause-specific mortality were assessed using Cox regression, adjusting for age, body mass index, typical cardiovascular risk factors, occupation, past physical activity, existing CVD disease, glucose levels and medication use. RESULTS: 821 and 808 women were included for knee and hand analyses, respectively. Compared with the knee Pain-/ROA- group, the Pain+/ROA- group had an increased risk of CVD-specific mortality (HR 2.93 (95% CI 1.47 to 5.85)), while the knee Pain+/ROA+ group had an increased HR of 1.97 (95% CI 1.23 to 3.17) for all-cause and 3.57 (95% CI 1.53 to 8.34) for CVD-specific mortality. We found no association between hand OA and mortality. CONCLUSION: We found a significantly increased risk of all-cause and CVD-specific mortality in women experiencing knee pain with or without ROA but not ROA alone. No relationship was found between hand OA and mortality risk. This suggests that knee pain, more than structural changes of OA is the main driver of excess mortality in patients with OA. PMID- 26543060 TI - Functional Limitations and Gender Differences: Neighborhood Effects. AB - Rates of functional limitations are consistently higher for women than for men, but it is not clear why. While some studies have examined individual risk factors, others have turned to broader social characteristics. We examined the effects of both individual and neighborhood characteristics associated with the functional limitations of older men and women. Multilevel structural equation models were developed using data from a random digit dial sample of 5,688 adults aged 50 to 74 years living in New Jersey. We found that greater numbers of fast food restaurants, storefronts, and supermarkets was associated with more functional limitations of women, while greater numbers of fast-food restaurants was the only neighborhood characteristic associated with more functional limitations of men. Functional limitations of women, but not men, are affected by multiple neighborhood characteristics. This research reveals that specific neighborhood contextual characteristics, not just poverty, are associated with the health of community-dwelling adults. PMID- 26543061 TI - Treatment of large overjet in Angle Class II: division 1 malocclusion with Andresen activators versus prefabricated functional appliances-a multicenter, randomized, controlled trial. AB - OBJECTIVES: The purpose of this study was to compare the clinical effectiveness in reducing large overjet between a prefabricated functional appliance (PFA) and a slightly modified Andresen activator (AA). SETTING AND SAMPLE POPULATION: Public Dental Service, Gothenburg, Sweden. PARTICIPANTS, STUDY DESIGN, AND METHODS: A multicentre, prospective randomized clinical trial was conducted with patients from 12 general dental practices. One hundred and five patients with an Angle Class II, division 1 malocclusion and an overjet of >=6mm were eligible for the study. Eight patients were excluded due to various reasons and the sample consisted thus of 97 subjects (44 girls, 53 boys) with a mean age of 10.3 years. The study was designed as intention to treat and the patients were randomly allocated by lottery to treatment with either a PFA or an AA. The PFA and AA group consisted of 57 subjects (28 girls, 29 boys) and 40 subjects (16 girls, 24 boys), respectively. Overjet, overbite, lip seal, and sagittal molar relationship were recorded before, at the end of treatment and 1-year post-treatment. Blinding was not performed. The endpoint of treatment was set to overjet <=3mm and after this a 6 months retention period followed. RESULTS: No significant difference was found in overjet, overbite, sagittal relation, and lip seal between the two groups for the total observation period. The treatment of 40 (70 per cent) patients with PFA and 21 (53 per cent) with AA were considered unsuccessful mainly due to poor compliance. LIMITATIONS: No cephalometric records were taken as only patient-centred clinical outcome were used as an indicator for treatment success. The criteria of reduction of overjet to as low as 3mm could have affected the success rate. CONCLUSION: No difference in effectiveness could be shown between PFAs and AAs in correcting overjet, overbite, sagittal molar relation, and lip seal. The success rate in treatment with both appliances is, however, low. REGISTRATION: This trial was registered in "FoU i Sverige" (http://www.fou.nu/is/sverige), registration number: 97131. PROTOCOL: The protocol was not published before trial commencement. PMID- 26543062 TI - "What is Palliative Care?" AB - BACKGROUND AND AIM: Americans rely on the Internet for health information, and people are likely to turn to online resources to learn about palliative care as well. The purpose of this study was to analyze online palliative care information pages to evaluate the breadth of their content. We also compared how frequently basic facts about palliative care appeared on the Web pages to expert rankings of the importance of those facts to understanding palliative care. DESIGN: Twenty six pages were identified. Two researchers independently coded each page for content. Palliative care professionals (n = 20) rated the importance of content domains for comparison with content frequency in the Web pages. RESULTS: We identified 22 recurring broad concepts about palliative care. Each information page included, on average, 9.2 of these broad concepts (standard deviation [SD] = 3.36, range = 5-15). Similarly, each broad concept was present in an average of 45% of the Web pages (SD = 30.4%, range = 8%-96%). Significant discrepancies emerged between expert ratings of the importance of the broad concepts and the frequency of their appearance in the Web pages ( rtau = .25, P > .05). CONCLUSION AND IMPLICATIONS: This study demonstrates that palliative care information pages available online vary considerably in their content coverage. Furthermore, information that palliative care professionals rate as important for consumers to know is not always included in Web pages. We developed guidelines for information pages for the purpose of educating consumers in a consistent way about palliative care. PMID- 26543063 TI - A Survey of Hospice and Palliative Care Physicians Regarding Palliative Sedation Practices. AB - CONTEXT: Patients nearing the end of life may experience symptoms that are refractory to standard therapeutic options. Physicians may consider palliative sedation to relieve intolerable suffering. There is limited clinical literature regarding preferred medications for palliative sedation. OBJECTIVES: To determine the preferred medications physicians use when implementing palliative sedation. METHODS: An Internet-based, cross-sectional survey of hospice and palliative care physicians in the United States. RESULTS: A link to the survey was e-mailed to 3130 physician members of the American Academy of Hospice and Palliative Medicine, of which 381 physicians completed the survey. Physicians were not required to answer all questions. Nearly all (n = 335, 99%) respondents indicated that palliative sedation may be used (acceptable by 73% [n = 248] for refractory symptoms and acceptable by 26% [n = 87] only for imminently dying patients). Seventy-nine percent (n = 252) believed that opioids should not be used to induce palliative sedation but should be continued to provide pain control. Midazolam was the most commonly selected first-line choice for palliative sedation (n = 155, 42%). The most commonly reported second-line agents for the induction of palliative sedation were lorazepam, midazolam (for those who did not select midazolam as first-line agent), and phenobarbital with a reported preference of 20% (n = 49), 19% (n = 46), and 17% (n = 40), respectively. CONCLUSION: Of the physicians surveyed, 99% (n = 335) felt that palliative sedation is a reasonable treatment modality. Midazolam was considered a drug of choice for inducing and maintaining sedation, and opioids were continued for pain control. PMID- 26543064 TI - The importance of family. PMID- 26543065 TI - Call for papers: service delivery models for people with intellectual disabilities in developing countries. PMID- 26543066 TI - Making comparative performance information more comprehensible: an experimental evaluation of the impact of formats on consumer understanding. AB - STUDY OBJECTIVES: We aimed to investigate how different presentation formats influence comprehension and use of comparative performance information (CPI) among consumers. METHODS: An experimental between-subjects and within-subjects design with manipulations of CPI presentation formats. We enrolled both consumers with lower socioeconomic status (SES)/cognitive skills and consumers with higher SES/cognitive skills, recruited through an online access panel. Respondents received fictitious CPI and completed questions about interpretation and information use. Between subjects, we tested (1) displaying an overall performance score (yes/no); (2) displaying a small number of quality indicators (5 vs 9); and (3) displaying different types of evaluative symbols (star ratings, coloured dots and word icons vs numbers and bar graphs). Within subjects, we tested the effect of a reduced number of healthcare providers (5 vs 20). Data were analysed using descriptive analysis, analyses of variance and paired-sampled t tests. RESULTS: A total of 902 (43%) respondents participated. Displaying an overall performance score and the use of coloured dots and word icons particularly enhanced consumer understanding. Importantly, respondents provided with coloured dots most often correctly selected the top three healthcare providers (84.3%), compared with word icons (76.6% correct), star ratings (70.6% correct), numbers (62.0%) and bars (54.2%) when viewing performance scores of 20 providers. Furthermore, a reduced number of healthcare providers appeared to support consumers, for example, when provided with 20 providers, 69.5% correctly selected the top three, compared with 80.2% with five providers. DISCUSSION: Particular presentation formats enhanced consumer understanding of CPI, most importantly the use of overall performance scores, word icons and coloured dots, and a reduced number of providers displayed. Public report efforts should use these formats to maximise impact on consumers. PMID- 26543067 TI - Procedural instruction in invasive bedside procedures: a systematic review and meta-analysis of effective teaching approaches. AB - IMPORTANCE: Optimal approaches to teaching bedside procedures are unknown. OBJECTIVE: To identify effective instructional approaches in procedural training. DATA SOURCES: We searched PubMed, EMBASE, Web of Science and Cochrane Library through December 2014. STUDY SELECTION: We included research articles that addressed procedural training among physicians or physician trainees for 12 bedside procedures. Two independent reviewers screened 9312 citations and identified 344 articles for full-text review. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data from full-text articles. MAIN OUTCOMES AND MEASURES: We included measurements as classified by translational science outcomes T1 (testing settings), T2 (patient care practices) and T3 (patient/public health outcomes). Due to incomplete reporting, we post hoc classified study outcomes as 'negative' or 'positive' based on statistical significance. We performed meta-analyses of outcomes on the subset of studies sharing similar outcomes. RESULTS: We found 161 eligible studies (44 randomised controlled trials (RCTs), 34 non-RCTs and 83 uncontrolled trials). Simulation was the most frequently published educational mode (78%). Our post hoc classification showed that studies involving simulation, competency-based approaches and RCTs had higher frequencies of T2/T3 outcomes. Meta-analyses showed that simulation (risk ratio (RR) 1.54 vs 0.55 for studies with vs without simulation, p=0.013) and competency-based approaches (RR 3.17 vs 0.89, p<0.001) were effective forms of training. CONCLUSIONS AND RELEVANCE: This systematic review of bedside procedural skills demonstrates that the current literature is heterogeneous and of varying quality and rigour. Evidence is strongest for the use of simulation and competency-based paradigms in teaching procedures, and these approaches should be the mainstay of programmes that train physicians to perform procedures. Further research should clarify differences among instructional methods (eg, forms of hands-on training) rather than among educational modes (eg, lecture vs simulation). PMID- 26543068 TI - Identifying patient safety problems associated with information technology in general practice: an analysis of incident reports. AB - OBJECTIVE: To identify the categories of problems with information technology (IT), which affect patient safety in general practice. DESIGN: General practitioners (GPs) reported incidents online or by telephone between May 2012 and November 2013. Incidents were reviewed against an existing classification for problems associated with IT and the clinical process impacted. PARTICIPANTS AND SETTING: 87 GPs across Australia. MAIN OUTCOME MEASURE: Types of problems, consequences and clinical processes. RESULTS: GPs reported 90 incidents involving IT which had an observable impact on the delivery of care, including actual patient harm as well as near miss events. Practice systems and medications were the most affected clinical processes. Problems with IT disrupted clinical workflow, wasted time and caused frustration. Issues with user interfaces, routine updates to software packages and drug databases, and the migration of records from one package to another generated clinical errors that were unique to IT; some could affect many patients at once. Human factors issues gave rise to some errors that have always existed with paper records but are more likely to occur and cause harm with IT. Such errors were linked to slips in concentration, multitasking, distractions and interruptions. Problems with patient identification and hybrid records generated errors that were in principle no different to paper records. CONCLUSIONS: Problems associated with IT include perennial risks with paper records, but additional disruptions in workflow and hazards for patients unique to IT, occasionally affecting multiple patients. Surveillance for such hazards may have general utility, but particularly in the context of migrating historical records to new systems and software updates to existing systems. PMID- 26543069 TI - The Evolution of an Inpatient Palliative Care Consultation Service in an Urban Teaching Hospital. AB - BACKGROUND: Research on inpatient palliative medicine reports quality-of-life outcomes and selected "hard" outcomes including pain scores, survival, and readmissions. OBJECTIVE: This case study reports the evolution of an inpatient palliative consultation (IPC) team to show how IPC induces culture change in a hospital that previously had no palliative care. DESIGN: Retrospective chart review. SETTING: A Catholic university-affiliated, inner-city hospital. POPULATION: A total of 1700 consecutive adult inpatients from May 2009 to October 2013. MEASURES: Consultation records enumerated demographics, code status, powers of attorney, referring physician, reason for consultation, and discharge destination. Deidentified data were uploaded to a spreadsheet. Simple descriptive statistics were calculated. RESULTS: Requests originated from internal medicine (24%), geriatrics (21%), neurology (including stroke and neurosurgery, 14.3%), medical intensive care unit (MICU, 12.2%), and hematology-oncology (10.3%). The MICU consults increased 17.6% over time. The numbers of consults nearly doubled after trainees began rounding with the service. Hospice discharges increased by 9.2%. Palliative management of in-hospital expirations increased 2- to 3-fold. The most common consultation requests were for pain and nonpain symptoms, establishing goals of care for patients experiencing clinical decline and convening family meetings in cases of divided judgment. CONCLUSION: We describe the evolution of palliative care in a safety-net hospital. Medicine services which are largely resident run adopted early. Specialty services that are attending driven adopted later. We believe house staff and nurses were the initial change agents. The number of consultations increased when house staff and students began rotating on the service suggesting unmet demand due to the limited supply of providers. PMID- 26543070 TI - Question 1: What is the best strategy to promote water consumption in children? PMID- 26543071 TI - Usage of unpublished paediatric data. AB - The European Paediatric Regulation (EC No 1901/2006) has three main objectives: increasing the number of appropriate medicines for children, increasing information on these medicines and stimulating high-quality ethical research with children. To contribute to the information, pharmaceutical companies were required under article 45 of the Regulation to submit existing paediatric studies to regulatory authorities for review and update of the product information. Nearly, 19 000 study reports have been identified for a thousand active substances. The data are being assessed by member states' competent authorities in collaboration with European Medicines Agency (EMA). After 7 years, 262 active substances have been assessed, all of the 62 centrally approved and nearly 200 nationally approved medicines. The review so far has led to 16 new paediatric indications, of importance in addressing previously unmet needs, in particular, in younger age groups. The information is being made publicly available in an EMA database accessible directly or through the public face of the European Clinical Trials Register. This will increase awareness of existing data that are useful to researchers and other healthcare professionals, and contribute to avoiding unnecessary duplication of paediatric trials. PMID- 26543072 TI - Case report: bullous Henoch-Schonlein purpura. PMID- 26543074 TI - Prognosis for Women With Multivessel Coronary Artery Disease. PMID- 26543073 TI - Watson-Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation. AB - RNA transcripts that include expanded CCUG repeats are associated with myotonic dystrophy type 2. Crystal structures of two CCUG-containing oligomers show that the RNA strands associate into slipped duplexes that contain noncanonical C-U pairs that have apparently undergone tautomeric transition or protonation resulting in an unusual Watson-Crick-like pairing. The overhanging ends of the duplexes interact forming U-U pairs, which also show tautomerism. Duplexes consisting of CCUG repeats are thermodynamically less stable than the trinucleotide repeats involved in the TRED genetic disorders, but introducing LNA residues increases their stability and raises the melting temperature of the studied oligomers by ~10 degrees C, allowing detailed crystallographic studies. Quantum mechanical calculations were performed to test the possibility of the tautomeric transitions or protonation within the noncanonical pairs. The results indicate that tautomeric or ionic shifts of nucleobases can manifest themselves in biological systems, supplementing the canonical "rules of engagement." PMID- 26543075 TI - Elongated Uvula Causing Chronic Cough: Role of the Modified Uvulopalatoplasty Procedure. AB - OBJECTIVE: A subset of patients previously diagnosed with idiopathic chronic cough were found to have an elongated uvula contacting the laryngeal surface of the epiglottis and inducing a cough reflex. These patients were successfully treated with an in-office modified uvulopalatoplasty procedure (mUPP) at our institution. We aim to further categorize this subset of patients and describe the mUPP that can potentially offer this group of patients cure for their chronic cough. STUDY DESIGN: Institutional Review Board-approved retrospective chart review. METHODS: Patient demographics, medical history, associated symptoms, prior treatment remedies, and response to mUPP were recorded and analyzed for 30 patients who underwent an in-office mUPP. RESULTS: The majority of patients were middle-aged, nonsmoking females with symptoms of globus sensation and a gag reflex when lying supine. 96.7% of patients reported complete resolution or noticeable improvement of their cough following mUPP. There were no complications from this in-office procedure in our study. CONCLUSIONS: The authors' main goals are to make other physicians aware of this under-recognized subset of patients with chronic cough who have an identifiable and treatable cause for their symptoms and to provide the steps of a simple and effective surgical solution to chronic cough in this group of patients. PMID- 26543076 TI - Identification of Novel Biomarker and Therapeutic Target Candidates for Diagnosis and Treatment of Follicular Adenoma. AB - Follicular adenoma is a type of benign and encapsulated nodule in the thyroid gland, but some adenomas have the potential to progress to follicular carcinoma. Therefore, it is important to monitor the state and progress of follicular adenoma in the clinic and discover drug development targets for the treatment of follicular adenoma to prevent its worsening to follicular carcinoma. Currently, the study of biomarkers and therapeutic targets lacks applications of up-to-date technologies, including proteomics and bioinformatics. To discover novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to directly compare follicular adenoma with normal thyroid tissue samples. The proteomics analysis revealed 114 protein biomarker candidates out of 1,780 identified and quantified proteins. A comprehensive approach to prioritize the biomarker candidates by category and rank revealed CD63, DDB1, TYMP, VDAC2, and DCXR as the top five biomarker candidates. Upstream regulator analysis using the Ingenuity Pathway Analysis (IPA) software discovered four therapeutic target candidates for follicular adenoma, including TGFB1, MYC, ANGPT2, and NFE2L2. This study provided biomarker and therapeutic target candidates for a follow-up study, which will facilitate monitoring and treatment of follicular adenoma. PMID- 26543077 TI - A Novel Approach to Evaluating Cancer Driver Gene Mutation Densities: Cytoskeleton-related Gene Candidates. AB - BACKGROUND: Oncoprotein genes are over-represented in statically defined, low mutation-frequency fractions of cancer genome atlas (TCGA) datasets, consistent with a higher driver mutation density. MATERIALS AND METHODS: We developed a "continuously variable fraction" (CVF) approach to defining high and low mutation frequency groups. RESULTS AND CONCLUSION: Using the CVF approach, an oncoprotein set was shown to be associated with a TCGA, low mutation-frequency group in nine distinct cancer types, versus six, for statically defined sets; and a tumor suppressor set was over-represented in the low mutation-frequency group in seven cancer types, notably including BRCA. The CVF approach identified single-mutation driver candidates, such as BRAF V600E in the thyroid cancer dataset. The CVF approach allowed investigation of cytoskeletal protein-related coding regions (CPCRs), leading to the conclusion that mutation of CPCRs occurs at a statistically significant, higher density in low mutation-frequency groups. Supporting online material for this article can be found at www.universityseminarassociates.com/Supporting_online_material_for_scholarly_pubs php. PMID- 26543078 TI - Ensuring Sample Quality for Biomarker Discovery Studies - Use of ICT Tools to Trace Biosample Life-cycle. AB - The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials. PMID- 26543079 TI - Oligo-based High-resolution aCGH Analysis Enhances Routine Cytogenetic Diagnostics in Haematological Malignancies. AB - BACKGROUND: The purpose of the present study was to evaluate the detection rate of genomic aberrations in haematological malignancies using oligobased array-CGH (oaCGH) analysis in combination with karyotyping and fluorescence in situ hybridization (FISH) analyses, and its feasibility in a clinical pragmatic approach. MATERIALS AND METHODS: The 4x180K Cancer Cytochip array was applied in 96 patients with various haematological malignancies in a prospective setting and in 41 acute myeloid leukemia (AML) patients retrospectively. RESULTS: Combined use of oaCGH analysis and karyotyping improved the overall detection rate in comparison to karyotyping-alone and vice versa. In cases with normal karyotypes oaCGH analysis detected genomic aberrations in 66% (39/60) of cases. In the group of simple karyotypes oaCGH analysis extended karyotypic findings in 39% (12/31) while oaCGH analysis extended the karyotypic findings in 89% (39/44) of cases with complex karyotypes. In 7% (5/75) of cases oaCGH analysis failed in detecting the observed abnormalities by karyotyping. CONCLUSION: oaCGH analysis is a valuable asset in routine cytogenetics of haematological malignancies. PMID- 26543080 TI - MTA1 Is Up-regulated in Colorectal Cancer and Is Inversely Correlated with Lymphatic Metastasis. AB - BACKGROUND: Metastasis-associated protein 1 (MTA1) plays an important role in tumourigenesis and progression of certain cancer types. In the current study, we analyzed the relationship between MTA1 expression and disease progression of colorectal cancer (CRC). MATERIALS AND METHODS: CRC tissues (n=93) and adjacent normal colorectal tissues (n=70) were analyzed by quantitative real-time polymerase chain reaction. MTA1 knockdown was established in RKO and HT115 cells using MTA1 siRNA. RESULTS: The expression of MTA1 was significantly increased in CRC tissues compared to paired normal colorectal tissues, but decreased expression of MTA1 was correlated with poor prognosis (higher lymph node involvement stage, TNM stage, local invasion and recurrence) that was associated with increased expression of VEGFC and -D and the receptor VEGFR3. CONCLUSION: MTA1 is up-regulated in CRC. MTA1 expression is inversely associated with lymphatic metastases and the expression of VEGFC, VEGFD and VEGFR3. PMID- 26543081 TI - Doxorubicin Affects Expression of Proteins of Neuronal Pathways in MCF-7 Breast Cancer Cells. AB - In the present article, we report on the semi-quantitative proteome analysis and related changes in protein expression of the MCF-7 breast cancer cell line following treatment with doxorubicin, using the precursor acquisition independent from ion count (PAcIFIC) mass spectrometry method. PAcIFIC represents a cost effective and easy-to-use proteomics approach, enabling for deep proteome sequencing with minimal sample handling. The acquired proteomic data sets were searched for regulated Reactome pathways and Gene Ontology annotation terms using a new algorithm (SetRank). Using this approach, we identified pathways with significant changes (<=0.05), such as chromatin organization, DNA binding, embryo development, condensed chromosome, sequence-specific DNA binding, response to oxidative stress and response to toxin, as well as others. These sets of pathways are already well-described as being susceptible to chemotherapeutic drugs. Additionally, we found pathways related to neuron development, such as central nervous system neuron differentiation, neuron projection membrane and SNAP receptor activity. These later pathways might indicate biological mechanisms on the molecular level causing the known side-effect of doxorubicin chemotherapy, characterized as cognitive impairment, also called 'chemo brain'. Mass spectrometry data are available via ProteomeXchange with identifier PXD002998. PMID- 26543082 TI - Contribution of DNA Double-strand Break Repair Gene XRCC3 Genotypes to Triple negative Breast Cancer Risk. AB - AIM: The DNA-repair gene X-ray repair cross-complementing group 3 (XRCC3) is important in DNA double-strand break repair and plays a critical part in initiation of carcinogenesis. Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype with no existing gene-targeting drugs and little knowledge on its genetic etiology. This study aimed to investigate the contribution of the XRCC3 genotype to individual TNBC susceptibility. MATERIALS AND METHODS: A total of 2,464 Taiwan citizens consisting of 1,232 breast cancer cases and 1,232 controls were enrolled in this case-control study, and genotyping of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539 and rs28903081 were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We also conducted risk-stratified sub-group analyses to determine the association between the genotype and age- and hormone related characteristics of breast cancer sub-groups. RESULTS: There was no significant difference between breast cancer and control groups in the distributions of the genotypic or allelic frequencies as for the XRCC3 rs1799794 (p=0.5195 and 0.9545), rs45603942 (p=0.3478 and 0.1449), rs861530 (p=0.4567 and 0.5081), rs3212057 (p=1.0000 and 1.0000), rs1799796 (p=0.8487 and 0.7315) and rs28903081 (p=1.0000 and 1.0000), respectively. However, the XRCC3 rs861539 TT genotype was more prevalent in patients with breast cancer [odds ratio (OR)=2.99, 95% confidence interval (CI)=1.62-5.55; p=0.0002], and especially among those who were younger than 55 years (OR=2.61, 95% CI=1.82-3.73; p=0.0001), with first menarche earlier than 12.2 years (OR=2.47, 95% CI=1.74-3.52; p=0.0001), with menopause at 49.0 years old or later (OR=2.53, 95% CI=1.76-3.62; p=0.0001), or with TNBC (OR=2.05, 95% CI=1.46-4.28; p=4.63*10(-4)). CONCLUSION: XRCC3 rs861539 TT is a potential predictive marker for TNBC in Taiwanese women and investigations in other populations are warranted for further universal application in cancer detection and prediction. PMID- 26543083 TI - Global Proteomic Profiling of Drosophila Ovary: A High-resolution, Unbiased, Accurate and Multifaceted Analysis. AB - BACKGROUND: Drosophila melanogaster ovary serves as an attractive model system for the investigation of the cell cycle, death, signaling, migration, differentiation, development and stemness. By employing the 3750/+ heterozygote fly strain that carries specific functions in the follicle cell compartment, and a reliable control in GAL4/UAS-based transgenic technology, we herein characterized the protein-expression profiling of D. melanogaster ovary by applying high-resolution proteomic tools and bioinformatics programs. MATERIALS AND METHODS: Whole-cell total protein extracts derived from 3750/+ fly ovaries were prepared under highly denaturing conditions and after tryptic digestion, their cognate peptides were processed to liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis in a high-resolution LTQ Orbitrap Elite instrument. Obtained protein data were analyzed through use of UniProt, DAVID, KEGG and PANTHER bioinformatics platforms. RESULTS: The 7,583 unique peptides identified show that fly ovary contains at least 2,103 single proteins, which are distributed to all egg chamber compartments, in cytoplasm, membrane and nucleus, compartmentalized into major cellular organelles, and categorized into critical macromolecular assemblies. Among the recognized specific functions, nucleic acid binding, hydrolase, oxidoreductase, transporter and vesicle-mediated trafficking activities were the most prevalent. Determinants implicated in cellular metabolism and gene expression are represented by ~41% and ~17% of the ovarian proteome, respectively. Surprisingly, several proteins were found engaged in aging, immune response and neurogenesis. All major signaling pathways were detected, while apoptotic and non-apoptotic cell death programs were also identified. Remarkably, proteins involved in tumor formation, neurodegenerative and inflammatory diseases were also recognized. The successful remodeling of the proteasome and nearly complete molecular reconstruction of the citrate cycle and fatty acid degradation pathways demonstrate the efficacy, accuracy and fidelity of our combined proteomics/bioinformatics approach. CONCLUSION: Global proteomic characterization of D. melanogaster ovary allows the discovery of novel regulators and pathways, and provides a systemic view of networks that govern ovarian pathophysiology and embryonic development in fly species as well in humans. PMID- 26543084 TI - Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer. AB - Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents. PMID- 26543085 TI - Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression. AB - BACKGROUND/AIM: Up-regulation of caveolin (CAV)-1 is associated with aggressive prostate cancer. Recently, it has been inferred that CAV2, a co-factor sub-type of CAV1, cross-talks with CAV1 and promotes tumor growth. We previously reported that plasma CAV1 levels are elevated in patients with castration-resistant prostate cancer (CRPC), but not in hormone-sensitive prostate cancer (non-CRPC), implying that CAV1 may be a therapeutic target for CRPC. However, a correlation of CAV1 and CAV2 expression in PC has not yet been reported. Herein, we analyzed associations between PC progression and plasma CAV1 and -2 in Japanese men, and expression of CAV1 and -2 in PC3 (CRPC) and LNCaP (non-CRPC) cell lines. MATERIALS AND METHODS: We investigated plasma samples from 36 patients with CRPC and 22 with non-CRPC. We used enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of CAV1 and -2, and examined correlations with clinicopathological characteristics such as Gleason grade and clinical T stage. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate CAV1 and CAV2 mRNA in PC cell lines. We also introduced CAV1 and CAV2-specific small interfering (siRNA) into PC3 cells to knock-down (KD) both molecules, and examined its influence on the expression of these genes between PC3 CAV1 and -2 KD cells and control cells. RESULTS: Plasma CAV1 and -2 levels in patients with CRPC were significantly higher than in those with non CRPC (CAV1, p=0.003; CAV2, p<0.001). Plasma levels of CAV1 and -2 were significantly correlated (p<0.001). However, we did not find any significant relationship between CAV1 or CAV2 expression and clinicopathological factors. ELISA and real-time qRT-PCR showed that both proteins and mRNAs in PC3 cells were significantly over-expressed compared to LNCaP cells (p<0.001). In PC3 CAV1 KD cells, expression of CAV2 was suppressed and confirmed the linkage of CAV2 KD and suppression of CAV1 expression. CONCLUSION: There was a significant correlation between plasma CAV-1 and -2 levels and progression of PC. CAV1 and -2 were highly expressed in the PC3 compared to the LNCaP cell line. Our findings support the potential of these molecules as therapeutic targets for CRPC. PMID- 26543086 TI - Cytotoxic Activities of Eosinophil Cationic Protein and Eosinophil-derived Neurotoxin: In Silico Analysis. AB - BACKGROUND: Eosinophil cationic protein (ECP) and eosinophil derived-neurotoxin (EDN) are homologous ribonuclease (RNAse) A family proteins. The objective of the present study was to in silico characterize ECP and EDN with respect to their cytotoxic activities. MATERIALS AND METHODS: Structural, physicochemical, and conserved domain characterizations were carried-out using open-source software, such as InterProScan, NetOGlyc, NetPhos and Discovery Studio 3.1. RESULTS: The proteins did not have atypical conserved domains. EDN had a greater number of glutamine amino acid residues, whereas ECP had a predominance of arginine. ECP had four possible N-glycosylation, three O-glycosylation and four phosphorylation sites. EDN had five putative N-glycosylation, three phosphorylation and no O glycosylation sites. CONCLUSION: The greater cationicity of ECP may be related to its higher cytotoxicity and to the fact that the varying post-translational modification profiles can generate functional differences from structural alteration. In vivo and in vitro studies need to be performed in order to confirm these predictions. PMID- 26543088 TI - Simultaneous Quantification of Syringic Acid and Kaempferol in Extracts of Bergenia Species Using Validated High-Performance Thin-Layer Chromatographic Densitometric Method. AB - A rapid, sensitive, selective and robust quantitative densitometric high performance thin-layer chromatographic method was developed and validated for separation and quantification of syringic acid (SYA) and kaempferol (KML) in the hydrolyzed extracts of Bergenia ciliata and Bergenia stracheyi. The separation was performed on silica gel 60F254 high-performance thin-layer chromatography plates using toluene : ethyl acetate : formic acid (5 : 4: 1, v/v/v) as the mobile phase. The quantification of SYA and KML was carried out using a densitometric reflection/absorption mode at 290 nm. A dense spot of SYA and KML appeared on the developed plate at a retention factor value of 0.61 +/- 0.02 and 0.70 +/- 0.01. A precise and accurate quantification was performed using linear regression analysis by plotting the peak area vs concentration 100-600 ng/band (correlation coefficient: r = 0.997, regression coefficient: R(2) = 0.996) for SYA and 100-600 ng/band (correlation coefficient: r = 0.995, regression coefficient: R(2) = 0.991) for KML. The developed method was validated in terms of accuracy, recovery and inter- and intraday study as per International Conference on Harmonisation guidelines. The limit of detection and limit of quantification of SYA and KML were determined, respectively, as 91.63, 142.26 and 277.67, 431.09 ng. The statistical data analysis showed that the method is reproducible and selective for the estimation of SYA and KML in extracts of B. ciliata and B. stracheyi. PMID- 26543089 TI - Use of microsatellite and SNP markers for biotype characterization in Hessian fly. AB - Exploration of the biotype structure of Hessian fly, Mayetiola destructor (Say) (Diptera: Cecidomyiidae), would improve our knowledge regarding variation in virulence phenotypes and difference in genetic background. Microsatellites (simple sequence repeats) and single-nucleotide polymorphisms (SNPs) are highly variable genetic markers that are widely used in population genetic studies. This study developed and tested a panel of 18 microsatellite and 22 SNP markers to investigate the genetic structure of nine Hessian fly biotypes: B, C, D, E, GP, L, O, vH9, and vH13. The simple sequence repeats were more polymorphic than the SNP markers, and their neighbor-joining trees differed in consequence. Microsatellites suggested a simple geographic association of related biotypes that did not progressively gain virulence with increasing genetic distance from a founder type. Use of the k-means clustering algorithm in the STRUCTURE program shows that the nine biotypes comprise six to eight populations that are related to geography or history within laboratory cultures. PMID- 26543090 TI - Phosphoinositide 3-kinase-delta regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress. AB - BACKGROUND: Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-delta and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-delta and its relationship with ER stress in fungus-induced allergic lung inflammation. METHODS: Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-delta regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis. RESULTS: Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K delta inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-delta inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K delta. CONCLUSIONS: These findings suggest that PI3K-delta regulates Af-induced steroid-resistant eosinophilic allergic lung inflammation through ER stress. PMID- 26543091 TI - Lymph node trafficking of regulatory T cells is prerequisite for immune suppression. AB - Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad inflammation. In addition, although blockage of CCR7 or CD62L had no effect on the immune suppressive function of the regulatory T cells per se, pretreatment of the regulatory T cells with either CCR7 or CD62L blocking antibodies prevented their recruitment into draining lymph nodes and concomitantly abrogated the immune suppressive effects of adoptively transferred regulatory T cells during footpad inflammation. Our data demonstrate the crucial role of lymph node localization in regulatory T cell-mediated immune suppression and suggest a probable hierarchy in the anatomic sites for optimal immune regulation. Elucidating the relationships between the transmigration characteristics of the regulatory T cells and their immune regulation function will provide insightful information for regulatory T cell-based cell therapy. PMID- 26543092 TI - Correction for Chen et al., Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection. PMID- 26543094 TI - Allergic Lung Inflammation Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice. AB - OBJECTIVE: Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. APPROACH AND RESULTS: Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions. ALI also increased plasma IgE, reduced plasma interleukin-5, and increased bronchioalveolar total inflammatory cell and eosinophil accumulation. Intraperitoneal administration of an anti-IgE antibody suppressed AAA lesion formation and reduced lesion inflammation, plasma IgE, and bronchioalveolar inflammation. Pre-establishment of ALI also increased AAA lesion size, lesion accumulation of macrophages and mast cells, media smooth muscle cell loss, and plasma IgE, reduced plasma interleukin-5, interleukin-13, and transforming growth factor-beta, and increased bronchioalveolar inflammation. Consequent production of ALI also doubled lesion size of pre-established AAA and increased lesion mast cell and T-cell accumulation, media smooth muscle cell loss, lesion cell proliferation and apoptosis, plasma IgE, and bronchioalveolar inflammation. In periaortic CaCl2 injury-induced AAA in mice, production of ALI also increased AAA formation, lesion inflammation, plasma IgE, and bronchioalveolar inflammatory cell accumulation. CONCLUSIONS: This study suggests a pathological link between airway allergic disease and AAA. Production of one disease aggravates the progression of the other. PMID- 26543095 TI - NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells. AB - OBJECTIVES: Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice. APPROACH AND RESULTS: Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta. CONCLUSIONS: These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis. PMID- 26543096 TI - Novel Pathways of Apolipoprotein A-I Metabolism in High-Density Lipoprotein of Different Sizes in Humans. AB - OBJECTIVE: A prevailing concept is that high-density lipoprotein (HDL) is secreted into the systemic circulation as a small mainly discoidal particle, which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. APPROACH AND RESULTS: We studied the metabolism of apolipoprotein A-I in 4 standard HDL sizes by endogenous isotopic labeling in 6 overweight adults with low HDLc and in 6 adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apolipoprotein A-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1 to 4 days and then was cleared. Enlargement of very small and medium to large and very large HDL and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower, whereas medium, large, and very large HDL were cleared faster in the low HDLc group. CONCLUSIONS: A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes across the common range of HDLc concentrations. PMID- 26543097 TI - Biomarkers: A Challenging Conundrum in Cardiovascular Disease. AB - The use of biomarkers has proven utility in cardiovascular medicine and holds great promise for future advances, but their application requires considerable rigor in thinking and methodology. Numerous confounding factors can cloud the clinical and investigative uses of biomarkers. Yet, the thoughtful and critical use of biomarkers can doubtless aid discovery of new pathogenic pathways, identify novel therapeutic targets, and provide a bridge between the laboratory and the clinic. Biomarkers can provide diagnostic and prognostic tools to the practitioner. The careful application of biomarkers can also help design and guide clinical trials required to establish the efficacy of novel interventions to improve patient outcomes. Point of care testing, technological advances, such as microfluidic and wearable devices, and the power of omics approaches all promise to elevate the potential contributions of biomarkers to discovery science, translation, clinical trials, and the practice of cardiovascular medicine. PMID- 26543098 TI - Genome-Edited Human Pluripotent Stem Cell-Derived Macrophages as a Model of Reverse Cholesterol Transport--Brief Report. AB - OBJECTIVE: To create isogenic human pluripotent stem cell-derived macrophages with and without ABCA1 expression as a model for reverse cholesterol transport. APPROACH AND RESULTS: The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) genome-editing system was used to introduce frameshift mutations into the coding sequence of ATP-binding cassette, subfamily A, member 1. Individual human pluripotent stem cell clones with deleterious mutations were identified, expanded, and differentiated into mature macrophages with a cytokine-based, feeder-free differentiation protocol. Wild type cells demonstrated effective cholesterol efflux to apoAI acceptor, whereas ABCA1(-/-) cells displayed significantly reduced efflux ability and increased expression of proinflammatory cytokines. CONCLUSIONS: Human pluripotent stem cell derived macrophages capable of reverse cholesterol transport can be rapidly generated and genetically edited with CRISPR/Cas9. Introduction of homozygous frameshift mutations results in loss of ABCA1 expression in differentiated macrophages and subsequent reduction of cholesterol efflux capability. This facile genome-editing approach and differentiation protocol pave the way for future studies of the molecular determinants of reverse cholesterol transport and other macrophage properties. PMID- 26543099 TI - Disruption of Physiological Balance Between Nitric Oxide and Endothelium Dependent Hyperpolarization Impairs Cardiovascular Homeostasis in Mice. AB - OBJECTIVE: Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel size-dependent manner; NO plays a dominant role in conduit arteries and EDH in resistance vessels. We have recently demonstrated that endothelial NO synthase (eNOS) is functionally suppressed in resistance vessels through caveolin-1 (Cav-1)-dependent mechanism, switching its function from NO to EDH/hydrogen peroxide generation in mice. Here, we examined the possible importance of the physiological balance between NO and EDH in cardiovascular homeostasis. APPROACH AND RESULTS: We used 2 genotypes of mice in which eNOS activity is genetically upregulated; Cav-1-knockout (Cav-1-KO) and endothelium specific eNOS transgenic (eNOS-Tg) mice. Isometric tension recordings and Langendorff experiments with isolated perfused hearts showed that NO-mediated relaxations were significantly enhanced, whereas EDH-mediated relaxations were markedly reduced in microcirculations. Importantly, impaired EDH-mediated relaxations of small mesenteric arteries from Cav-1-KO mice were completely rescued by crossing the mice with those with endothelium-specific overexpression of Cav-1. Furthermore, both genotypes showed altered cardiovascular phenotypes, including cardiac hypertrophy in Cav-1-KO mice and hypotension in eNOS-Tg mice. Finally, we examined cardiac responses to chronic pressure overload by transverse aortic constriction in vivo. When compared with wild-type mice, both Cav-1-KO and eNOS-Tg mice exhibited reduced survival after transverse aortic constriction associated with accelerated left ventricular systolic dysfunction, reduced coronary flow reserve, and enhanced myocardial hypoxia. CONCLUSIONS: These results indicate that excessive endothelium-derived NO with reduced EDH impairs cardiovascular homeostasis in mice in vivo. PMID- 26543100 TI - Association Between Cholesterol Efflux Capacity and Atherosclerotic Cardiovascular Disease in Patients With Familial Hypercholesterolemia. AB - OBJECTIVE: Patients with familial hypercholesterolemia (FH) are at high risk for premature atherosclerotic cardiovascular disease (ASCVD), especially because of long-term exposure to high low-density lipoprotein cholesterol levels. It has been reported that low-density lipoprotein-lowering therapy delays the onset of ASCVD. However, it still remains difficult to prevent it. Therefore, novel biomarkers and therapeutic targets are necessary to evaluate and prevent atherosclerosis in FH. The aim of this study was to investigate associations of cholesterol efflux capacity with the presence of ASCVD and clinical features in patients with heterozygous FH. APPROACH AND RESULTS: We measured cholesterol efflux capacity in 227 patients with heterozygous FH under pharmaceutical treatment. Seventy-six (33.5%) of them were known to have ASCVD. In a logistic regression analysis adjusted for risk factors, increased efflux capacity was associated with decreased risk of ASCVD even after the addition of high-density lipoprotein cholesterol level as a covariate (odds ratio per 1-SD increase, 0.95; 95% confidence interval, 0.90-0.99; P<0.05). Decreased cholesterol efflux capacity was associated with the presence of corneal arcus after adjusting for age and sex. In addition, inverse relationships between cholesterol efflux capacity and Achilles tendon thickness, as well as carotid intima-media thickness, were observed after adjustment for age, sex, and traditional cardiovascular risk factors. CONCLUSIONS: Cholesterol efflux capacity was independently and inversely associated with the presence of ASCVD in heterozygous FH. In view of residual risks after treatment with statins, cholesterol efflux capacity might be a novel biomarker and a therapeutic target for preventing atherosclerosis in patients with FH. PMID- 26543101 TI - Microsomal Prostaglandin E Synthase-1-Derived PGE2 Inhibits Vascular Smooth Muscle Cell Calcification. AB - OBJECTIVE: Chronic administration of selective cyclooxygenase-2 (COX-2) inhibitors leads to an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. Vascular smooth muscle cell (VSMC) calcification, a common complication of chronic kidney disease, is directly related to cardiovascular morbidity and mortality. Here, we tested whether specific COX-2 inhibition affects vascular calcification during chronic renal failure. APPROACH AND RESULTS: The COX-2-specific inhibitors NS398 and SC236 significantly increased high-phosphate (Pi)-induced VSMC calcification. Similarly, COX-2(-/-) VSMCs, COX-2(-/-) aortas rings treated with high Pi and adenine diet-induced COX-2(-/-) chronic renal failure mice displayed enhanced calcium deposition. Metabolomic analysis revealed the differential suppression of PGE2 production by COX-1- and COX-2-specific inhibitors in high-Pi-stimulated VSMCs, indicating the involvement of PGE2 during COX-2 inhibition-aggravated vascular calcification. Indeed, exogenous PGE2 reduced alkaline phosphatase activity, osteogenic transdifferentiation, apoptosis, and calcification of VSMCs. In accordance, downregulation of microsomal prostaglandin E synthase (mPGES)-1 in VSMCs, mPGES-1(-/-) aorta with high-Pi stimulation and mPGES-1(-/-) chronic renal failure mice resulted in enhanced vascular mineralization. Further applications of RNAi and specific antagonists for PGE2 receptors indicated EP4 may mediate PGE2-inhibited vascular calcification. CONCLUSIONS: Our data revealed the pivotal role of COX-2-mPGES-1-PGE2 axis in vascular calcification. The selective inhibition of COX-2 or mPGES-1 may increase the risk of calcification and subsequent adverse cardiovascular events during chronic renal failure. PMID- 26543102 TI - Monitoring Cellular Phosphorylation Signaling Pathways into Chromatin and Down to the Gene Level. AB - Protein phosphorylation, one of the most common and important modifications of acute and reversible regulation of protein function, plays a dominant role in almost all cellular processes. These signaling events regulate cellular responses, including proliferation, differentiation, metabolism, survival, and apoptosis. Several studies have been successfully used to identify phosphorylated proteins and dynamic changes in phosphorylation status after stimulation. Nevertheless, it is still rather difficult to elucidate precise complex phosphorylation signaling pathways. In particular, how signal transduction pathways directly communicate from the outer cell surface through cytoplasmic space and then directly into chromatin networks to change the transcriptional and epigenetic landscape remains poorly understood. Here, we describe the optimization and comparison of methods based on thiophosphorylation affinity enrichment, which can be utilized to monitor phosphorylation signaling into chromatin by isolation of phosphoprotein containing nucleosomes, a method we term phosphorylation-specific chromatin affinity purification (PS-ChAP). We utilized this PS-ChAP(1) approach in combination with quantitative proteomics to identify changes in the phosphorylation status of chromatin-bound proteins on nucleosomes following perturbation of transcriptional processes. We also demonstrate that this method can be employed to map phosphoprotein signaling into chromatin containing nucleosomes through identifying the genes those phosphorylated proteins are found on via thiophosphate PS-ChAP-qPCR. Thus, our results showed that PS-ChAP offers a new strategy for studying cellular signaling and chromatin biology, allowing us to directly and comprehensively investigate phosphorylation signaling into chromatin to investigate if these pathways are involved in altering gene expression. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD002436. PMID- 26543104 TI - Draft Genome Sequence of Bacillus Species from the Rhizosphere of the Desert Plant Rhazya stricta. AB - In order to better understand the ecology and diversity of microbes in the rhizosphere of desert plants, we undertook a survey of Bacillus species isolated from soil around Rhazya stricta plants from the area around Jeddah, in The Kingdom, Saudi Arabia. We have sequenced the genomes of 8 Bacillus isolates representing four different species. PMID- 26543103 TI - Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus. AB - Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAalpha1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAalpha1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID- 26543105 TI - First Complete Genome Sequence of Felis catus Gammaherpesvirus 1. AB - We sequenced the complete genome of Felis catus gammaherpesvirus 1 (FcaGHV1) from lymph node DNA of an infected cat. The genome includes a 121,556-nucleotide unique region with 87 predicted open reading frames (61 gammaherpesvirus conserved and 26 unique) flanked by multiple copies of a 966-nucleotide terminal repeat. PMID- 26543106 TI - Complete Genome Sequence of Bartonella ancashensis Strain 20.00, Isolated from the Blood of a Patient with Verruga Peruana. AB - Here we present the complete genome sequence of Bartonella ancashensis strain 20.00, isolated from the blood of a Peruvian patient with verruga peruana, known as Carrion's disease. Bartonella ancashensis is a Gram-negative bacillus, phylogenetically most similar to Bartonella bacilliformis, the causative agent of Oroya fever and verruga peruana. PMID- 26543107 TI - Genome Sequence of Complex HIV-1 Unique Recombinant Forms Sharing a Common Recombination Breakpoint Identified in Malaysia. AB - Three strains of HIV-1 unique recombinant forms (URFs) descended from subtypes B, B', and CRF01_AE were identified among people who inject drugs in Kuala Lumpur, Malaysia. These three URFs shared a common recombination breakpoint in the reverse transcriptase region, indicating frequent linkage within the drug injecting networks in Malaysia. PMID- 26543108 TI - Whole-Genome Sequences of Mycobacterium bovis Strain MbURU-001, Isolated from Fresh Bovine Infected Samples. AB - Bovine tuberculosis in cattle has a high incidence in Uruguay, where it is considered a disease of national importance. We present the genome sequence of Mycobacterium bovis strain MbURU-001, isolated from pectoral lymph nodes of a bovine host from a cattle farm. PMID- 26543109 TI - Complete Genome Sequences of Four Escherichia coli ST95 Isolates from Bloodstream Infections. AB - Finished genome sequences are presented for four Escherichia coli strains isolated from bloodstream infections at San Francisco General Hospital. These strains provide reference sequences for four major fimH-identified sublineages within the multilocus sequence type (MLST) ST95 group, and provide insights into pathogenicity and differential antimicrobial susceptibility within this group. PMID- 26543110 TI - Draft Genome Sequences of Two Propionibacterium acnes Strains Isolated from Progressive Macular Hypomelanosis Lesions of Human Skin. AB - Propionibacterium acnes is a Gram-positive bacterium that is prevalent on human skin. It has been associated with skin disorders such as acne vulgaris and progressive macular hypomelanosis (PMH). Here, we report draft genome sequences of two type III P. acnes strains, PMH5 and PMH7, isolated from PMH skin lesions. PMID- 26543111 TI - Genome Sequence of Type Strain Lysinibacillus macroides DSM 54T. AB - Lysinibacillus macroides DSM 54(T) is a Gram-positive, spore-forming bacterium. Here, we report the 4,866,035-bp genome sequence of Lysinibacillus macroides DSM 54(T), which will accelerate the application of degrading xylan and provide useful information for genomic taxonomy and phylogenomics of Bacillus-like bacteria. PMID- 26543112 TI - Complete Genome Sequence of Multidrug-Resistant Clinical Isolate Mycobacterium tuberculosis 187.0, Used To Study the Effect of Drug Susceptibility Reversion by the New Medicinal Drug FS-1. AB - Complete genome sequence of the multidrug-resistant clinical isolate Mycobacterium tuberculosis SCAID 187.0 containing several drug-resistance mutations is presented. This strain is used in experiments to study genomic and population changes leading to reversion of susceptibility to the 1st line anti tuberculosis (TB) drugs under the influence of a new medicinal drug FS-1. PMID- 26543113 TI - Draft Genome Sequence of Mycobacterium peregrinum Strain CSUR P2098. AB - Mycobacterium peregrinum is a nonpigmented rapid growing nontuberculosis species belonging to the Mycobacterium fortuitum group. The draft genome of M. peregrinum type I CSUR P2098 comprises 7,109,836 bp exhibiting a 66.23% G+C content, 6,894 protein-coding genes, and 100 predicted RNA genes. Its genome analysis suggests this species differs from Mycobacterium senegalense. PMID- 26543114 TI - Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain UCD-SED8 (Phylum Gammaproteobacteria). AB - Here, we present the draft genome sequence of Pseudoalteromonas tetraodonis UCD SED8, a marine bacterium normally associated with the production of tetrodotoxin in pufferfish. This strain was isolated from sediment samples surrounding Zostera marina roots collected from Bodega Marine, California. The assembly consists of 4,017,727 bp contained in 35 contigs. PMID- 26543115 TI - Complete Genome Sequence of Methanosphaerula palustris E1-9CT, a Hydrogenotrophic Methanogen Isolated from a Minerotrophic Fen Peatland. AB - Here, we report the complete genome sequence (2.92 Mb) of Methanosphaerula palustris E1-9C(T), a methanogen isolated from a minerotrophic fen. This is the first genome report of the Methanosphaerula genus, within the Methanoregulaceae family, in the Methanomicrobiales order. E1-9C(T) relatives are found in a wide range of ecological and geographical settings. PMID- 26543116 TI - Draft Genome Sequence of Cercospora arachidicola, Causal Agent of Early Leaf Spot in Peanuts. AB - Cercospora arachidicola, causal agent of early leaf spot, is an economically important peanut pathogen. Lack of genetic information about this fungus prevents understanding the role that potentially diverse genotypes may have in peanut breeding programs. Here, we report for the first time a draft genome sequence of C. arachidicola. PMID- 26543117 TI - Whole-Genome Sequence of "Candidatus Profftella armatura" from Diaphorina citri in Guangdong, China. AB - The genome of "Candidatus Profftella armatura" strain YCPA from Diaphorina citri in Guangdong, China, was sequenced. The strain has a chromosome of 457,565 bp, 24.3% G+C content, 364 predicted open reading frames (ORFs), and 38 RNAs, and a plasmid, pYCPA54, of 5,458 bp with 23.9% G+C content and 5 ORFs. PMID- 26543118 TI - Complete Genome Sequence of a Phenanthrene Degrader, Burkholderia sp. HB-1 (NBRC 110738). AB - The phenanthrene-degrading Burkholderia sp. HB-1 was isolated from a phenanthrene enrichment culture seeded with a pristine farm soil sample. We report the complete genome sequence of HB-1, which has been deposited to the stock culture (NBRC 110738) at Biological Resource Center, National Institute of Technology and Evaluation (NITE), Tokyo, Japan. The genome of strain HB-1 comprises two circular chromosomes of 4.1 Mb and 3.1 Mb. The finishing was facilitated by the computational tools GenoFinisher, AceFileViewer, and ShortReadManager. PMID- 26543119 TI - Complete Genome Sequence of the Human Gut Symbiont Roseburia hominis. AB - We report here the complete genome sequence of the human gut symbiont Roseburia hominis A2-183(T) (= DSM 16839(T) = NCIMB 14029(T)), isolated from human feces. The genome is represented by a 3,592,125-bp chromosome with 3,405 coding sequences. A number of potential functions contributing to host-microbe interaction are identified. PMID- 26543120 TI - Draft Genome Sequences for Five Strains of Trabulsiella odontotermitis, Isolated from Heterotermes sp. Termite Gut. AB - Trabulsiella odontotermitis represents a novel species in the genus Trabulsiella with no complete genome reported yet. Here, we describe the draft genome sequences of five isolates from termites present in the north of Mexico, which have an interesting pool of genes related to cellulose degradation with biotechnological application. PMID- 26543121 TI - Genome Sequence of Citrobacter sp. CtB7.12, Isolated from the Gut of the Desert Subterranean Termite Heterotermes aureus. AB - The draft genome of Citrobacter sp. CtB7.12, isolated from termite gut, is presented here. This organism has been reported as a cellulolytic bacterium, which is biotechnologically important because it can be used as a gene donor for the ethanol and biofuel industries. PMID- 26543122 TI - Complete Genome Sequence of the Campylobacter ureolyticus Clinical Isolate RIGS 9880. AB - The emerging pathogen Campylobacter ureolyticus has been isolated from human and animal genital infections, human periodontal disease, domestic and food animals, and from cases of human gastroenteritis. We report the whole-genome sequence of the human clinical isolate RIGS 9880, which is the first closed genome for C. ureolyticus. PMID- 26543123 TI - Draft Genome Sequence of Porphyromonas gingivalis Strain Ando Expressing a 53 Kilodalton-Type Fimbrilin Variant of Mfa1 Fimbriae. AB - Periodontopathic Porphyromonas gingivalis strain Ando abundantly expresses a 53 kDa-type Mfa1 fimbria. Here, we report the draft genome sequence of Ando, with a size of 2,229,994 bp, average G+C content of 48.4%, and 1,755 predicted protein coding sequences. PMID- 26543124 TI - Genome Sequence of a Potential Probiotic Strain, Lactobacillus fermentum HFB3, Isolated from a Human Gut. AB - A draft genome sequence of 2.04 Mb is reported for Lactobacillus fermentum HFB3, which is a lactic acid bacterium with probiotic properties. The gene-coding clusters also predicted the presence of genes responsible for probiotic characteristics. PMID- 26543125 TI - Draft Genome Sequences of Nine Streptococcus suis Strains Isolated in the United States. AB - Streptococcus suis is a swine pathogen responsible for economic losses to the pig industry worldwide. Additionally, it is a zoonotic agent that can cause severe infections in those in close contact with infected pigs and/or who consume uncooked or undercooked pork products. Here, we report nine draft genome sequences of S. suis. PMID- 26543126 TI - Whole-Genome Sequence of Leptospira interrogans Serovar Hardjo Subtype Hardjoprajitno Strain Norma, Isolated from Cattle in a Leptospirosis Outbreak in Brazil. AB - Leptospirosis is caused by pathogenic bacteria of the genus Leptospira spp. This neglected re-emergent disease has global distribution and relevance in veterinary production. Here, we report the whole-genome sequence and annotation of Leptospira interrogans serovar Hardjo subtype Hardjoprajitno strain Norma, isolated from cattle in a livestock leptospirosis outbreak in Brazil. PMID- 26543127 TI - Genome Sequence of Porphyromonas gingivalis Strain AJW4. AB - Porphyromonas gingivalis is associated with oral and systemic diseases. Strain specific P. gingivalis invasion phenotypes have been correlated with disease presentation in infected laboratory animals. Here, we present the genome sequence of AJW4, a minimally invasive strain, with a single contig of 2,372,492 bp and a G+C content of 48.27%. PMID- 26543128 TI - Genome Assembly of Chryseobacterium polytrichastri ERMR1:04, a Psychrotolerant Bacterium with Cold Active Proteases, Isolated from East Rathong Glacier in India. AB - We report here the genome assembly of a psychrotolerant bacterium, Chryseobacterium polytrichastri ERMR1:04, which secretes cold-active proteases. The bacterium was isolated from a pristine location, the East Rathong Glacier in the Sikkim Himalaya. The 5.53-Mb genome provides insight into the cold-active industrial enzyme and adaptation in the cold environment. PMID- 26543129 TI - Draft Genome Sequence of Caedibacter varicaedens, a Kappa Killer Endosymbiont Bacterium of the Ciliate Paramecium biaurelia. AB - Caedibacter varicaedens is a kappa killer endosymbiont bacterium of the ciliate Paramecium biaurelia. Here, we present the draft genome sequence of C. varicaedens. PMID- 26543130 TI - Complete Genome Sequences of Campylobacter jejuni Strains RM3196 (233.94) and RM3197 (308.95) Isolated from Patients with Guillain-Barre Syndrome. AB - Infections with Campylobacter jejuni subsp. jejuni are a leading cause of foodborne gastroenteritis and the most prevalent infection preceding Guillain Barre syndrome (GBS). This study describes the genomes of C. jejuni subsp. jejuni HS:41 strains RM3196 (233.94) and RM3197 (308.95) that were isolated from patients with GBS in Cape Town, South Africa. PMID- 26543131 TI - Draft Genome Sequence of Mycobacterium neworleansense Strain ATCC 49404T. AB - Mycobacterium neworleansense is a rapid growing nontuberculosis species belonging to the Mycobacterium fortuitum complex. The draft genome of M. neworleansense ATCC 49404(T) comprises 6,287,317 bp exhibiting a 66.85% G+C content, 5,997 protein-coding genes, and 89 predicted RNA genes. PMID- 26543132 TI - Draft Genome Sequence of "Candidatus Liberibacter asiaticus" from Diaphorina citri in Guangdong, China. AB - The draft genome sequence of "Candidatus Liberibacter asiaticus" strain YCPsy from an Asian citrus psyllid (Diaphorina citri) in Guangdong, China, is reported here. The YCPsy strain has a genome size of 1,233,647 bp, 36.5% G+C content, 1,171 open reading frames (ORFs), and 53 RNAs. PMID- 26543133 TI - Genome Sequence of Acinetobacter baumannii Strain 10441_14 Belonging to ST451, Isolated from India. AB - Acinetobacter baumannii resistance to carbapenems is of global concern. Here, we report the 3.9 Mb draft genome of a cerebrospinal fluid isolate of A. baumannii strain 10441_14 which is carbapenem resistant and belongs to ST451. This genome will further help in the understanding of the drug resistance mechanism, epidemiology, and pathology of this bacterium. PMID- 26543134 TI - Paying for sex-only for people with disabilities? AB - Thomsen (2015) argues that people with disabilities should be granted an exception to a general prohibition on paying for sex. In this response, we argue that Thomsen's call for an exception does not withstand careful scrutiny. The concerns that appear to motivate his argument point instead, we argue, to a case for legalization of prostitution, coupled with sensible health and safety regulations. PMID- 26543135 TI - Fortresses against infection: time for new defences? PMID- 26543138 TI - Swine Flu Looming at the Indo-Pak Border: Is Pakistan Ready to Tackle the Potential Threat? PMID- 26543139 TI - The Need to Develop a Statutory Regulatory Body for the Practice of Al-Hijama. PMID- 26543141 TI - Community health champions ignite enthusiasm for improving wellbeing in South East London [corrected]. PMID- 26543142 TI - Twists and turns in the war with infectious disease. PMID- 26543143 TI - Infectious disease prevention in the home and community: closing the circle. PMID- 26543144 TI - The journey of the germ: commentary on routes of infection and targeted hand hygiene. PMID- 26543145 TI - Partnering with broadcast and print media for risk communication: EVD control in Rivers State, Nigeria. PMID- 26543146 TI - Antibiotic resistance awareness: spreading the word, not the worry. PMID- 26543147 TI - Lessons learned from the Chikungunya outbreak in the Caribbean. PMID- 26543148 TI - Has India's TB programme undermined TB advocacy? PMID- 26543149 TI - Integrated disease surveillance in India - progress and pitfalls. PMID- 26543150 TI - Putting communities at the heart of public health. PMID- 26543151 TI - Compost and Legionella longbeachae: an emerging infection? AB - Human disease caused by Legionella species is dominated by Legionella pneumophila, the main causative agent in cases of Legionnaires' disease. However, other species are known to cause infection, for example, Legionella longbeachae causes an equivalent number of cases of disease as L. pneumophila in Australia and New Zealand. Infection with L. longbeachae is commonly associated with exposure to composts and potting soils, and cases of infection with this organism have been increasing in Europe over the past ten years. The increase in incidence may be linked to factors such as increased awareness of clinical presentation, or due to changing formulation of growing media, although it should be noted that the presence of Legionella species in growing media does not correlate with the number of cases currently seen. This is likely due to the variables associated with infection, for example, host factors such as smoking or underlying health conditions, or difference in growing media storage or climate, especially warm humid conditions, which may affect survival and growth of these organisms in the growing media environment. There are numerous unknowns in this area and collaboration between growing media manufacturers and researchers, as well as more awareness among diagnosing clinicians, laboratory staff and the general public is necessary to reduce risk. More research is needed before definitive conclusions can be drawn: L. pneumophila research currently dominates the field and it is likely that the overreliance on diagnostic techniques such as the urinary antigen test, which is specific for L. pneumophila Sg 1, is detrimental to the diagnosis of L. longbeachae infection. PMID- 26543153 TI - Light acclimation of photosynthesis in two closely related firs (Abies pinsapo Boiss. and Abies alba Mill.): the role of leaf anatomy and mesophyll conductance to CO2. AB - Leaves growing in the forest understory usually present a decreased mesophyll conductance (gm) and photosynthetic capacity. The role of leaf anatomy in determining the variability in gm among species is known, but there is a lack of information on how the acclimation of gm to shade conditions is driven by changes in leaf anatomy. Within this context, we demonstrated that Abies pinsapo Boiss. experienced profound modifications in needle anatomy to drastic changes in light availability that ultimately led to differential photosynthetic performance between trees grown in the open field and in the forest understory. In contrast to A. pinsapo, its congeneric Abies alba Mill. did not show differences either in needle anatomy or in photosynthetic parameters between trees grown in the open field and in the forest understory. The increased gm values found in trees of A. pinsapo grown in the open field can be explained by occurrence of stomata at both needle sides (amphistomatous needles), increased chloroplast surface area exposed to intercellular airspace, decreased cell wall thickness and, especially, decreased chloroplast thickness. To the best of our knowledge, the role of such drastic changes in ultrastructural needle anatomy in explaining the response of gm to the light environment has not been demonstrated in field conditions. PMID- 26543154 TI - Warming delays autumn declines in photosynthetic capacity in a boreal conifer, Norway spruce (Picea abies). AB - Climate change, via warmer springs and autumns, may lengthen the carbon uptake period of boreal tree species, increasing the potential for carbon sequestration in boreal forests, which could help slow climate change. However, if other seasonal cues such as photoperiod dictate when photosynthetic capacity declines, warmer autumn temperatures may have little effect on when carbon uptake capacity decreases in these species. We investigated whether autumn warming would delay photosynthetic decline in Norway spruce (Picea abies (L.) H. Karst.) by growing seedlings under declining weekly photoperiods and weekly temperatures either at ambient temperature or a warming treatment 4 degrees C above ambient. Photosynthetic capacity was relatively constant in both treatments when weekly temperatures were >8 degrees C, but declined rapidly at lower temperatures, leading to a delay in the autumn decline in photosynthetic capacity in the warming treatment. The decline in photosynthetic capacity was not related to changes in leaf nitrogen or chlorophyll concentrations, but was correlated with a decrease in the apparent fraction of leaf nitrogen invested in Rubisco, implicating a shift in nitrogen allocation away from the Calvin cycle at low autumn growing temperatures. Our data suggest that as the climate warms, the period of net carbon uptake will be extended in the autumn for boreal forests dominated by Norway spruce, which could increase total carbon uptake in these forests. PMID- 26543155 TI - 'Beckett on the Wards': medical humanities pedagogy and 'compassionate care'. PMID- 26543156 TI - Teenage perceptions of electronic cigarettes in Scottish tobacco-education school interventions: co-production and innovative engagement through a pop-up radio project. AB - AIMS: This article thematically analyses spontaneous responses of teenagers and explores their perceptions of electronic cigarettes (e-cigarettes) with a focus on smoking cessation from data collected for research exploring Scottish secondary school students' recall of key messages from tobacco-education interventions and any influence on perceptions and behaviours. METHODS: E cigarettes were not included in the research design as they did not feature in interventions. However, in discussions in all participating schools, e-cigarettes were raised by students unprompted by researchers. Seven of 19 publicly funded schools in the region opted to participate. Groups of 13- to 16-year-olds were purposely selected to include a range of aptitudes, non-smokers, smokers, males and females. A total of 182 pupils took part. Data were generated through three co-produced classroom radio tasks with pupils (radio quiz, sitcom, factual interviewing), delivered by a researcher and professional broadcast team. All pupils were briefly interviewed by a researcher. Activities were recorded and transcribed verbatim and the researcher discussed emerging findings with the broadcast team. Data were analysed using NVivo and transcripts making reference to e-cigarettes examined further using inductive thematic analysis. RESULTS: Key themes of their impressions of e-cigarettes were easy availability and price; advertising; the products being safer or healthier, addiction and nicotine; acceptability and experiences of use; and variety of flavours. CONCLUSIONS: This was a qualitative study in one region, and perception of e-cigarettes was not an a priori topic. However, it provides insights into youth perceptions of e cigarettes. How they discerned e-cigarettes reflects their marketing environment. The relative harmlessness of nicotine, affordability of e-cigarettes, coolness of vaping, absence of second-hand harms and availability of innovative products are all key marketing features. Conflicting messages on safety, efficacy, potential 'gateway' to smoking and nicotine may be contributing to teenagers' confusion. The allure of 'youthful cool' to vaping offers no public health gain, so children should be protected from misleading promotion. Consistent tobacco-education initiatives need to account for this popular trend. PMID- 26543157 TI - Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production. AB - Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Maranon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin. PMID- 26543158 TI - Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. AB - The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 A resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. PMID- 26543159 TI - Molecular basis for histone N-terminal methylation by NRMT1. AB - NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 A. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 A costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif. PMID- 26543160 TI - GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. AB - Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Their combined effects orchestrate cellular adaptation to amino acid levels, but how their activities are coordinated remains poorly understood. Here, we demonstrate an important link between GCN2 and mTORC1 signaling. Upon deprivation of various amino acids, activated GCN2 up-regulates ATF4 to induce expression of the stress response protein Sestrin2, which is required to sustain repression of mTORC1 by blocking its lysosomal localization. Moreover, Sestrin2 induction is necessary for cell survival during glutamine deprivation, indicating that Sestrin2 is a critical effector of GCN2 signaling that regulates amino acid homeostasis through mTORC1 suppression. PMID- 26543162 TI - Mifepristone is a Vasodilator Due to the Inhibition of Smooth Muscle Cells L-Type Ca2+ Channels. AB - Derived from the estrane progestins, mifepristone was the first synthetic steroid of this class employed as abortifacient in the first months of pregnancy. Mifepristone reduces high potassium-induced contraction and prevents calcium induced contraction. At the vascular level, mifepristone induces direct relaxation in rat and human arteries, and this effect seems to be endothelium- and NO independent, suggesting that the vascular smooth muscle is its target. Moreover, mifepristone's effect could involve the modulation of different calcium channels. The aim of the present study is to analyze the involvement of calcium channels in the relaxation induced by mifepristone on vascular smooth muscle cells (VSMCs). Planar cell surface area (PCSA) technique was used to analyze the effect of mifepristone on the VSMC contractility, and the whole cell configuration of patch-clamp technique to measure the activity of L-type Ca(2+) channels (LTCC) in A7r5 cells. Regarding the PCSA technique, mifepristone induced relaxation of the VSMC previously contracted by different agents. Also, a rapid inhibitory effect on basal and BAY K8644-stimulated calcium current was observed, which indicates that this drug has the ability to block LTCC. These results suggest that mifepristone induces relaxation on the VSMCs due to the inhibition of the calcium channels. PMID- 26543161 TI - Structural basis for substrate recognition by the human N-terminal methyltransferase 1. AB - alpha-N-terminal methylation represents a highly conserved and prevalent post translational modification, yet its biological function has remained largely speculative. The recent discovery of alpha-N-terminal methyltransferase 1 (NTMT1) and its physiological substrates propels the elucidation of a general role of alpha-N-terminal methylation in mediating DNA-binding ability of the modified proteins. The phenotypes, observed from both NTMT1 knockdown in breast cancer cell lines and knockout mouse models, suggest the potential involvement of alpha N-terminal methylation in DNA damage response and cancer development. In this study, we report the first crystal structures of human NTMT1 in complex with cofactor S-adenosyl-L-homocysteine (SAH) and six substrate peptides, respectively, and reveal that NTMT1 contains two characteristic structural elements (a beta hairpin and an N-terminal extension) that contribute to its substrate specificity. Our complex structures, coupled with mutagenesis, binding, and enzymatic studies, also present the key elements involved in locking the consensus substrate motif XPK (X indicates any residue type other than D/E) into the catalytic pocket for alpha-N-terminal methylation and explain why NTMT1 prefers an XPK sequence motif. We propose a catalytic mechanism for alpha-N terminal methylation. Overall, this study gives us the first glimpse of the molecular mechanism of alpha-N-terminal methylation and potentially contributes to the advent of therapeutic agents for human diseases associated with deregulated alpha-N-terminal methylation. PMID- 26543163 TI - Importance of Health and Social Care Research into Gender and Sexual Minority Populations in Nepal. AB - Despite progressive legislative developments and increased visibility of sexual and gender minority populations in the general population, mass media often report that this population face a wide range of discrimination and inequalities. LGBT (lesbian, gay, and bisexual, and transgender) populations have not been considered as priority research populations in Nepal. Research in other geographical settings has shown an increased risk of poor mental health, violence, and suicide and higher rates of smoking, as well as alcohol and drugs use among LGBT populations. They are also risk for lifestyle-related illness such as cancer, diabetes, and heart diseases. Currently, in Nepal, there is a lack of understanding of health and well-being, social exclusion, stigma, and discrimination as experienced by these populations. Good-quality public health research can help design and implement targeted interventions to the sexual and gender minority populations of Nepal. PMID- 26543165 TI - Is there a future for surgery as a profession? PMID- 26543164 TI - Factors Influencing Access to Sexual Health Care Among Behaviorally Bisexual Men in Vientiane, Laos: A Qualitative Exploration. AB - In Laos, men who have sex with men (MSM) are disproportionately affected by HIV, and bisexual behavior among men is common. We conducted a qualitative study to explore access and influences on sexual health care seeking among bisexual men in Vientiane. In 2013, behaviorally bisexual men were recruited from bars, clubs and dormitories for 5 focus group discussions and 11 in-depth interviews. Participants (aged 18-35 years) commonly reported high-risk sexual behaviors, yet most had never been tested for HIV, and none reported testing for sexually transmitted infections. Common barriers to testing were low perception of risk, expectation of symptoms, fear of HIV, shyness, perceived stigma, confidentiality concerns, and waiting times. Many men were unaware of available services. Most clinics cannot provide comprehensive HIV and sexually transmitted infection services. Strategies are needed to generate demand for testing, improve the capacity of sexual health care providers, and promote available services among behaviorally bisexual men in Vientiane. PMID- 26543166 TI - Role of Sonography in Surgical Decision Making for Iatrogenic Spinal Accessory Nerve Injuries: A Paradigm Shift. AB - The spinal accessory nerve (SAN) is susceptible to iatrogenic injury in the posterior cervical triangle. Early diagnosis and management of suspected SAN transection injuries are crucial in the restoration of shoulder stability and function. Although neurologic examination and electrodiagnostic testing can assess SAN function, they cannot assess nerve continuity. We report the use of sonography to prospectively evaluate the SAN in 6 patients with suspected iatrogenic SAN injury. Sonography directly visualized SAN transection in 4 cases, whereas sonographic findings were reported as "probable" transection in the fifth case and was nondiagnostic in the sixth case in the setting of extensive scarring. PMID- 26543167 TI - Importance of Pulse Repetition Frequency Adjustment for 3- and 4-Dimensional Power Doppler Quantification. AB - OBJECTIVES: To determine the influence of the pulse repetition frequency (PRF) and wall motion filter on the 3-dimensional (3D) power Doppler vascularization flow index (VFI) and volumetric pulsatility index (PI) obtained from spatiotemporal image correlation (STIC) data sets acquired from a common carotid artery of a healthy participant. METHODS: We acquired 11 STIC data sets, 1 for each PRF value ranging from 0.6 to 9.0 kHz. Vascularization-flow index and volumetric PI values were determined from the 440 static 3D data sets contained in these STIC data sets. Additionally, 3 sets of radio-frequency data were acquired for offline processing of different wall motion filter values for PRF values of 0.6, 3.3, and 10 kHz. RESULTS: We constructed VFI curves and observed 2 patterns: a flattened pattern with a low PRF and a triphasic pattern with a high PRF, correlating with the known pulsed wave Doppler profile of this vessel. Volumetric PI values were around 0 for low PRF settings and increased with increasing PRF. Analysis of the radiofrequency data showed that increasing wall motion filter values gradually filtered out the low-velocity power Doppler signals while retaining the higher-velocity ones, allowing the distinction of integrated power Doppler signal velocity throughout the cardiac cycle. CONCLUSIONS: We conclude that the PRF and wall motion filter dramatically influence 3D power Doppler indices and the volumetric PI, and the use of PRF values in which minimum VFI values are measured during the diastolic phase in the spectral Doppler wave may validate the use of the volumetric PI. PMID- 26543168 TI - Use of Lung Ultrasound to Assess the Efficacy of an Alveolar Recruitment Maneuver in Rabbits With Acute Respiratory Distress Syndrome. AB - OBJECTIVES: To investigate the application of lung ultrasound (US) in the evaluation and implementation of alveolar recruitment maneuvers in acute respiratory distress syndrome (ARDS). METHODS: Twelve rabbits with saline lavage induced lung injury were randomly divided into 2 groups: one with alveolar recruitment guided by lung US and the other with alveolar recruitment guided by maximal oxygenation. Recruitment maneuvers were applied according to a stepwise incremental positive end-expiratory pressure method in both groups. In the oxygenation group, a sum of the partial pressures of oxygen and carbon dioxide exceeding 400 mm Hg was used to define adequate recruitment. In the lung US group, a new protocol for reaeration in US-guided lung recruitment was used to guide treatment. Evaluation by lung US, respiratory mechanical parameters, the Smith pathologic score (Crit Care Med 1997; 25:1888-1897), and wet-to-dry ratio were compared between the groups. RESULTS: Opening pressure was significantly higher in the lung US group (mean +/- SD, 23.4 +/- 3.4 cm H2O) than the oxygenation group (18.7 +/- 2.1 cm H2O; P < .05). The reaeration score in the lung US group significantly increased during alveolar recruitment (6.5 +/- 1.6 points at baseline versus 13.8 +/- 3.0 points after completion; P < .05). Lung compliance, dead space shunts, the Smith pathologic score, and tissue wet-to-dry ratio, however, were not significantly different between the groups. CONCLUSIONS: Lung US is an effective means of evaluating and guiding alveolar recruitment in ARDS. Compared with the maximal oxygenation-guided method, the protocol for reaeration in US-guided lung recruitment achieved a higher opening pressure, resulted in greater improvements in lung aeration, and substantially reduced lung heterogeneity in ARDS. PMID- 26543169 TI - Using Acoustic Structure Quantification During B-Mode Sonography for Evaluation of Hashimoto Thyroiditis. AB - OBJECTIVES: This study aimed to evaluate the usefulness of Acoustic Structure Quantification (ASQ; Toshiba Medical Systems Corporation, Nasushiobara, Japan) values in the diagnosis of Hashimoto thyroiditis using B-mode sonography and to identify a cutoff ASQ level that differentiates Hashimoto thyroiditis from normal thyroid tissue. METHODS: A total of 186 thyroid lobes with Hashimoto thyroiditis and normal thyroid glands underwent sonography with ASQ imaging. The quantitative results were reported in an echo amplitude analysis (Cm(2)) histogram with average, mode, ratio, standard deviation, blue mode, and blue average values. Receiver operating characteristic curve analysis was performed to assess the diagnostic ability of the ASQ values in differentiating Hashimoto thyroiditis from normal thyroid tissue. Intraclass correlation coefficients of the ASQ values were obtained between 2 observers. RESULTS: Of the 186 thyroid lobes, 103 (55%) had Hashimoto thyroiditis, and 83 (45%) were normal. There was a significant difference between the ASQ values of Hashimoto thyroiditis glands and those of normal glands (P < .001). The ASQ values in patients with Hashimoto thyroiditis were significantly greater than those in patients with normal thyroid glands. The areas under the receiver operating characteristic curves for the ratio, blue average, average, blue mode, mode, and standard deviation were: 0.936, 0.902, 0.893, 0.855, 0.846, and 0.842, respectively. The ratio cutoff value of 0.27 offered the best diagnostic performance, with sensitivity of 87.38% and specificity of 95.18%. The intraclass correlation coefficients ranged from 0.86 to 0.94, which indicated substantial agreement between the observers. CONCLUSIONS: Acoustic Structure Quantification is a useful and promising sonographic method for diagnosing Hashimoto thyroiditis. Not only could it be a helpful tool for quantifying thyroid echogenicity, but it also would be useful for diagnosis of Hashimoto thyroiditis. PMID- 26543170 TI - Sonographic Differentiation Between Schwannomas and Neurofibromas in the Musculoskeletal System. AB - OBJECTIVES: The purpose of this study was to determine key features and define a strategy for differentiation between schwannomas and neurofibromas using sonography. METHODS: This retrospective study was approved by the Institutional Review Board at our hospital, and informed consent was waived. We reviewed sonograms of pathologically proven schwannomas and neurofibromas of the extremities and body wall. On grayscale images, tumors were evaluated on the basis of their size, maximum-to-minimum diameter ratio, shape, contour, margin, location, encapsulation, echogenicity, echo texture, cystic changes, presence of intratumoral calcifications, presence of a target sign, and presence of an entering or exiting nerve. If an entering or exiting nerve was identified, the nerve-tumor position and nerve-tumor transition were characterized. On color Doppler images, the presence and amount of vascularity were evaluated. Student t tests were used for analysis of continuous variables (size, maximum-to-minimum diameter ratio, and age); chi(2) and Fisher exact tests were used for analysis of categorical variables. RESULTS: A total of 146 pathologically proven tumors, including 115 schwannomas and 31 neurofibromas of the extremities and body wall, were included. The maximum diameter, maximum-to-minimum diameter ratio, contour, cystic portion, nerve-tumor position, nerve-tumor transition, and vascularity were significantly different in schwannomas versus neurofibromas (P < .05), and a lobulated contour, fusiform shape, and hypovascularity of neurofibromas could be helpful for differentiation when a prediction model is considered. The nerve tumor position, nerve-tumor transition, and maximum-to-minimum diameter ratio were also significantly different between groups (P < .05) and thus could be useful for differentiation of neurogenic tumors. CONCLUSIONS: Sonographic findings are helpful in differentiating between schwannomas and neurofibromas. PMID- 26543171 TI - TESS: an R package for efficiently simulating phylogenetic trees and performing Bayesian inference of lineage diversification rates. AB - Many fundamental questions in evolutionary biology entail estimating rates of lineage diversification (speciation-extinction) that are modeled using birth death branching processes. We leverage recent advances in branching-process theory to develop a flexible Bayesian framework for specifying diversification models-where rates are constant, vary continuously, or change episodically through time-and implement numerical methods to estimate parameters of these models from molecular phylogenies, even when species sampling is incomplete. We enable both statistical inference and efficient simulation under these models. We also provide robust methods for comparing the relative and absolute fit of competing branching-process models to a given tree, thereby providing rigorous tests of biological hypotheses regarding patterns and processes of lineage diversification. AVAILABILITY AND IMPLEMENTATION: The source code for TESS is freely available at http://cran.r-project.org/web/packages/TESS/ CONTACT: Sebastian.Hoehna@gmail.com. PMID- 26543172 TI - Fast Optimized Cluster Algorithm for Localizations (FOCAL): a spatial cluster analysis for super-resolved microscopy. AB - MOTIVATION: Single-molecule localization microscopy (SMLM) microscopy provides images of cellular structure at a resolution an order of magnitude below what can be achieved by conventional diffraction limited techniques. The concomitantly larger data sets generated by SMLM require increasingly efficient image analysis software. Density based clustering algorithms, with the most ubiquitous being DBSCAN, are commonly used to quantitatively assess sub-cellular assemblies. DBSCAN, however, is slow, scaling with the number of localizations like O(n log (n)) at best, and it's performance is highly dependent upon a subjectively selected choice of parameters. RESULTS: We have developed a grid-based clustering algorithm FOCAL, which explicitly accounts for several dominant artifacts arising in SMLM image reconstructions. FOCAL is fast and efficient, scaling like O(n), and only has one set parameter. We assess DBSCAN and FOCAL on experimental dSTORM data of clusters of eukaryotic RNAP II and PALM data of the bacterial protein H NS, then provide a detailed comparison via simulation. FOCAL performs comparable and often superior to DBSCAN while yielding a significantly faster analysis. Additionally, FOCAL provides a novel method for filtering out of focus clusters from complex SMLM images. AVAILABILITY AND IMPLEMENTATION: The data and code are available at: http://www.utm.utoronto.ca/milsteinlab/resources/Software/FOCAL/ CONTACT: josh.milstein@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26543173 TI - Exact quantification of cellular robustness in genome-scale metabolic networks. AB - MOTIVATION: Robustness, the ability of biological networks to uphold their functionality in spite of perturbations, is a key characteristic of all living systems. Although several theoretical approaches have been developed to formalize robustness, it still eludes an exact quantification. Here, we present a rigorous and quantitative approach for the structural robustness of metabolic networks by measuring their ability to tolerate random reaction (or gene) knockouts. RESULTS: In analogy to reliability theory, based on an explicit consideration of all possible knockout sets, we exactly quantify the probability of failure for a given network function (e.g. growth). This measure can be computed if the network's minimal cut sets (MSCs) are known. We show that even in genome-scale metabolic networks the probability of (network) failure can be reliably estimated from MSCs with lowest cardinalities. We demonstrate the applicability of our theory by analyzing the structural robustness of multiple Enterobacteriaceae and Blattibacteriaceae and show a dramatically low structural robustness for the latter. We find that structural robustness develops from the ability to proliferate in multiple growth environments consistent with experimentally found knowledge. CONCLUSION: The probability of (network) failure provides thus a reliable and easily computable measure of structural robustness and redundancy in (genome-scale) metabolic networks. AVAILABILITY AND IMPLEMENTATION: Source code is available under the GNU General Public License at https://github.com/mpgerstl/networkRobustnessToolbox CONTACT: juergen.zanghellini@boku.ac.at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26543174 TI - meRanTK: methylated RNA analysis ToolKit. AB - The significance and function of posttranscriptional cytosine methylation in poly(A)RNA attracts great interest but is still poorly understood. High throughput sequencing of RNA treated with bisulfite (RNA-BSseq) or subjected to enrichment techniques like Aza-IP or miCLIP enables transcriptome wide studies of this particular modification at single base pair resolution. However, to date, there are no specialized software tools available for the analysis of RNA-BSseq or Aza-IP data. Therefore, we developed meRanTK, the first publicly available tool kit which addresses the special demands of high-throughput RNA cytosine methylation data analysis. It provides fast and easy to use splice-aware bisulfite sequencing read mapping, comprehensive methylation calling and identification of differentially methylated cytosines by statistical analysis of single- and multi-replicate experiments. Application of meRanTK to RNA-BSseq or Aza-IP data produces accurate results in standard compliant formats. AVAILABILITY AND IMPLEMENTATION: meRanTK, source code and test data are released under the GNU GPLv3+ license and are available at http://icbi.at/software/meRanTK/ CONTACT: dietmar.rieder@i-med.ac.at. PMID- 26543175 TI - A hidden Markov random field-based Bayesian method for the detection of long range chromosomal interactions in Hi-C data. AB - MOTIVATION: Advances in chromosome conformation capture and next-generation sequencing technologies are enabling genome-wide investigation of dynamic chromatin interactions. For example, Hi-C experiments generate genome-wide contact frequencies between pairs of loci by sequencing DNA segments ligated from loci in close spatial proximity. One essential task in such studies is peak calling, that is, detecting non-random interactions between loci from the two dimensional contact frequency matrix. Successful fulfillment of this task has many important implications including identifying long-range interactions that assist interpreting a sizable fraction of the results from genome-wide association studies. The task - distinguishing biologically meaningful chromatin interactions from massive numbers of random interactions - poses great challenges both statistically and computationally. Model-based methods to address this challenge are still lacking. In particular, no statistical model exists that takes the underlying dependency structure into consideration. RESULTS: In this paper, we propose a hidden Markov random field (HMRF) based Bayesian method to rigorously model interaction probabilities in the two-dimensional space based on the contact frequency matrix. By borrowing information from neighboring loci pairs, our method demonstrates superior reproducibility and statistical power in both simulation studies and real data analysis. AVAILABILITY AND IMPLEMENTATION: The Source codes can be downloaded at: http://www.unc.edu/~yunmli/HMRFBayesHiC CONTACT: ming.hu@nyumc.org or yunli@med.unc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26543176 TI - Shape component analysis: structure-preserving dimension reduction on biological shape spaces. AB - MOTIVATION: Quantitative shape analysis is required by a wide range of biological studies across diverse scales, ranging from molecules to cells and organisms. In particular, high-throughput and systems-level studies of biological structures and functions have started to produce large volumes of complex high-dimensional shape data. Analysis and understanding of high-dimensional biological shape data require dimension-reduction techniques. RESULTS: We have developed a technique for non-linear dimension reduction of 2D and 3D biological shape representations on their Riemannian spaces. A key feature of this technique is that it preserves distances between different shapes in an embedded low-dimensional shape space. We demonstrate an application of this technique by combining it with non-linear mean shift clustering on the Riemannian spaces for unsupervised clustering of shapes of cellular organelles and proteins. AVAILABILITY AND IMPLEMENTATION: Source code and data for reproducing results of this article are freely available at https://github.com/ccdlcmu/shape_component_analysis_Matlab The implementation was made in MATLAB and supported on MS Windows, Linux and Mac OS. CONTACT: geyang@andrew.cmu.edu. PMID- 26543177 TI - Assessment of v-gel supraglottic airway device placement in cats performed by inexperienced veterinary students. AB - Endotracheal intubation has been associated with several complications in cats. The v-gel supraglottic airway device (SGAD) has been developed to adapt to the unique oropharynx of the cat and to overcome these complications. Thirty-three cats were randomly assigned to receive an endotracheal tube (ETT group) or a v gel SGAD (v-gel group) after induction of general anaesthesia. Third year veterinary students without previous clinical experience placed these devices under direct supervision of an anaesthesiologist. Amount of propofol, number of attempts, time required to secure the airway, leakage around the device, signs of upper airway discomfort and food consumption were compared between the two groups. The v-gel group required less propofol (P=0.03), less time (P<0.01) and fewer attempts (P<0.01) to secure the cats' airway. The incidence of leakage was lower for the v-gel group immediately after placement of the device (P<0.01) and 60 minutes after induction of general anaesthesia (P=0.04). Cats that received the v-gel SGAD presented a lower incidence of upper airway discomfort immediately after the device was removed (P=0.03) and recorded a higher food consumption score (P=0.03). The v-gel SGAD is a feasible way to secure the airway of healthy cats when performed by inexperienced personnel. PMID- 26543178 TI - Measuring Driving-Related Attitudes Among Older Adults: Psychometric Evidence for the Decisional Balance Scale Across Time and Gender. AB - PURPOSE OF THE STUDY: The Decisional Balance Scale (DBS) was developed to assess older adults' attitudes related to driving and includes both intrapersonal and interpersonal motivations for driving. This study examined the psychometric properties of the DBS ratings across 3 time points in a sample of 928 older drivers who participated in the Canadian Driving Research Initiative for Vehicular Safety in the Elderly (Candrive). DESIGN AND METHODS: Measurement invariance of the DBS was assessed longitudinally and across gender. RESULTS: Confirmatory factor analyses revealed that a two-factor model (positive and negative attitudes) for both driving beliefs related to the self and other provided a good fit to the data at each time point. Measurement invariance was supported across time and gender. Significant associations between the DBS factor scores and other driving measures (e.g., perceived driving ability and self regulatory driving practices) provided evidence of convergent validity. IMPLICATIONS: The DBS appears to be a robust instrument for measuring attitudes toward driving and is recommended for continued use in future research on driving behaviors with older adults. PMID- 26543179 TI - Delirium Screening: A Systematic Review of Delirium Screening Tools in Hospitalized Patients. AB - BACKGROUND: Delirium occurs commonly in hospitalized older patients but is poorly recognized. Although there are a plethora of validated delirium screening tools, it is unclear which tool best suits particular populations. PURPOSE: To evaluate validation studies of delirium screening tools in non-critically ill hospital inpatients and provide guidance on the choice of screening tool. METHODS: The MEDLINE, CINAHL, and PsychInfo databases were searched for studies comparing delirium bedside screening tools with either the Diagnostic and Statistical Manual or International Classification of Diseases defined diagnosis of delirium in hospital inpatients. Information was also drawn from conference proceedings and discussion with delirium researchers. RESULTS: Thirty-one studies describing 21 delirium screening tools were included in the systematic review. The majority of studies were conducted across a broad range of inpatient settings internationally in elderly inpatients, including patients with dementia but most excluded nonnative language speakers. IMPLICATIONS: The Confusion Assessment Method was the most widely used instrument to identify delirium, however, specific training is required to ensure optimum performance. The Delirium Rating Scale and its revised version performed best in the psychogeriatric population but requires an operator with psychiatric training. The Nurses' Delirium Screening Checklist appears best suited to the surgical and recovery room setting. The Single Question in Delirium shows promise in oncology patients. The Memorial Delirium Assessment Scale, while demonstrating good measures of validity in the surgical and palliative care setting, may be better used a measure of delirium severity. The 4As Test performed well when delirium was superimposed on dementia, but it requires further study. PMID- 26543185 TI - A Quarter Century of Glycobiology. PMID- 26543194 TI - Interdisciplinary innovations are key to effective use of quantitative biological information. PMID- 26543186 TI - Symbol Nomenclature for Graphical Representations of Glycans. PMID- 26543195 TI - Biosecurity in the age of Big Data: a conversation with the FBI. AB - New scientific frontiers and emerging technologies within the life sciences pose many global challenges to society. Big Data is a premier example, especially with respect to individual, national, and international security. Here a Special Agent of the Federal Bureau of Investigation discusses the security implications of Big Data and the need for security in the life sciences. PMID- 26543196 TI - Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles. AB - Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point "snapshot" of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes--cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)--as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. PMID- 26543197 TI - The role of functional data in interpreting the effects of genetic variation. AB - Progress in DNA-sequencing technologies has provided a catalogue of millions of DNA variants in the human population, but characterization of the functional effects of these variants has lagged far behind. For example, sequencing of tumor samples is driving an urgent need to classify whether or not mutations seen in cancers affect disease progression or treatment effectiveness or instead are benign. Furthermore, mutations can interact with genetic background and with environmental effects. A new approach, termed deep mutational scanning, has enabled the quantitative assessment of the effects of thousands of mutations in a protein. However, this type of experiment is carried out in model organisms, tissue culture, or in vitro; typically addresses only a single biochemical function of a protein; and is generally performed under a single condition. The current challenge lies in using these functional data to generate useful models for the phenotypic consequences of genetic variation in humans. PMID- 26543198 TI - Big Data in Caenorhabditis elegans: quo vadis? AB - A clear definition of what constitutes "Big Data" is difficult to identify, but we find it most useful to define Big Data as a data collection that is complete. By this criterion, researchers on Caenorhabditis elegans have a long history of collecting Big Data, since the organism was selected with the idea of obtaining a complete biological description and understanding of development. The complete wiring diagram of the nervous system, the complete cell lineage, and the complete genome sequence provide a framework to phrase and test hypotheses. Given this history, it might be surprising that the number of "complete" data sets for this organism is actually rather small--not because of lack of effort, but because most types of biological experiments are not currently amenable to complete large scale data collection. Many are also not inherently limited, so that it becomes difficult to even define completeness. At present, we only have partial data on mutated genes and their phenotypes, gene expression, and protein-protein interaction--important data for many biological questions. Big Data can point toward unexpected correlations, and these unexpected correlations can lead to novel investigations; however, Big Data cannot establish causation. As a result, there is much excitement about Big Data, but there is also a discussion on just what Big Data contributes to solving a biological problem. Because of its relative simplicity, C. elegans is an ideal test bed to explore this issue and at the same time determine what is necessary to build a multicellular organism from a single cell. PMID- 26543200 TI - Single-cell phenomics in budding yeast. AB - The demand for phenomics, a high-dimensional and high-throughput phenotyping method, has been increasing in many fields of biology. The budding yeast Saccharomyces cerevisiae, a unicellular model organism, provides an invaluable system for dissecting complex cellular processes using high-resolution phenotyping. Moreover, the addition of spatial and temporal attributes to subcellular structures based on microscopic images has rendered this cell phenotyping system more reliable and amenable to analysis. A well-designed experiment followed by appropriate multivariate analysis can yield a wealth of biological knowledge. Here we review recent advances in cell imaging and illustrate their broad applicability to eukaryotic cells by showing how these techniques have advanced our understanding of budding yeast. PMID- 26543199 TI - Forces, fluctuations, and self-organization in the nucleus. AB - We address several processes and domains in the nucleus wherein holding the perspective of physics either reveals a conundrum or is likely to enable progress. PMID- 26543201 TI - Reproducible quantitative proteotype data matrices for systems biology. AB - Historically, many mass spectrometry-based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by advances in mass spectrometry, the proteomics field has thus recently shifted focus toward the reproducible quantification of proteins across a large number of biological samples. This provides the foundation to move away from pure enumeration of identified proteins toward quantitative matrices of many proteins measured across multiple samples. It is argued here that data matrices consisting of highly reproducible, quantitative, and unbiased proteomic measurements across a high number of conditions, referred to here as quantitative proteotype maps, will become the fundamental currency in the field and provide the starting point for downstream biological analysis. Such proteotype data matrices, for example, are generated by the measurement of large patient cohorts, time series, or multiple experimental perturbations. They are expected to have a large effect on systems biology and personalized medicine approaches that investigate the dynamic behavior of biological systems across multiple perturbations, time points, and individuals. PMID- 26543202 TI - Quantitative nature of overexpression experiments. AB - Overexpression experiments are sometimes considered as qualitative experiments designed to identify novel proteins and study their function. However, in order to draw conclusions regarding protein overexpression through association analyses using large-scale biological data sets, we need to recognize the quantitative nature of overexpression experiments. Here I discuss the quantitative features of two different types of overexpression experiment: absolute and relative. I also introduce the four primary mechanisms involved in growth defects caused by protein overexpression: resource overload, stoichiometric imbalance, promiscuous interactions, and pathway modulation associated with the degree of overexpression. PMID- 26543204 TI - The Journal of Medicine and Philosophy would like to Thank the following Guest Reviewers for their help during this past year. PMID- 26543205 TI - Defra seeks views on proposals to modernise the RCVS Council. PMID- 26543206 TI - NOAH expresses concern about parliamentary antibiotics report. PMID- 26543207 TI - Surveillance centre closure plans 'to be put on hold'. PMID- 26543203 TI - Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome. AB - BACKGROUND: SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. METHODS: We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. RESULTS: We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. CONCLUSIONS: We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype. PMID- 26543208 TI - International contributions recognised. PMID- 26543209 TI - Bluetongue in France: a role for wildlife in the latest outbreaks? PMID- 26543210 TI - Equine vet reprimanded for prepurchase examination and certification errors. PMID- 26543211 TI - Award for contributions to equine surgery. PMID- 26543212 TI - Veterinary medicines update. AB - The following information has been produced for Veterinary Record by the Veterinary Medicines Directorate (VMD) to provide an update for veterinary surgeons on recent changes to marketing authorisations for veterinary medicines in the UK and on other relevant issues. PMID- 26543213 TI - US task force launches action plan to tackle AMR in production agriculture. PMID- 26543214 TI - The rise of the referral sector. AB - The private referral sector in the UK has grown rapidly over the past 20 years. Continuing Veterinary Record's series of articles discussing the state of different sectors of the veterinary profession, Dick White considers how the sector has evolved and how it might continue to develop. PMID- 26543215 TI - Role of vaccination in dairy herd health and productivity. PMID- 26543216 TI - Use of antibiotics in animals and people. PMID- 26543217 TI - Correction. PMID- 26543218 TI - Shorter sentences. PMID- 26543219 TI - Diagnosis and treatment of canine neuropathic pain. PMID- 26543226 TI - Getting to grips with science. PMID- 26543227 TI - Second-year student diary. PMID- 26543228 TI - Caveolin-1 regulates cancer cell metabolism via scavenging Nrf2 and suppressing MnSOD-driven glycolysis. AB - Aerobic glycolysis is an indispensable component of aggressive cancer cell metabolism. It also distinguishes cancer cells from most healthy cell types in the body. Particularly for this reason, targeting the metabolism to improve treatment outcomes has long been perceived as a potentially valuable strategy. In practice, however, our limited knowledge of why and how metabolic reprogramming occurs has prevented progress towards therapeutic interventions that exploit the metabolic peculiarities of tumors. We recently described that in breast cancer, MnSOD upregulation is both necessary and sufficient to activate glycolysis. Here, we focused on determining the molecular mechanisms of MnSOD upregulation. We found that Caveolin-1 (Cav-1) is a central component of this mechanism due to its suppressive effects of NF-E2-related factor 2 (Nrf2), a transcription factor upstream of MnSOD. In transformed MCF10A(Er/Src) cells, Cav-1 loss preceded the activation of Nrf2 and its induction of MnSOD expression. Consistently, with previous observations, MnSOD expression secondary to Nrf2 activation led to an increase in the glycolytic rate dependent on mtH2O2 production and the activation of AMPK. Moreover, rescue of Cav-1 expression in a breast cancer cell line (MCF7) suppressed Nrf2 and reduced MnSOD expression. Experimental data were reinforced by epidemiologic nested case-control studies showing that Cav-1 and MnSOD are inversely expressed in cases of invasive ductal carcinoma, with low Cav-1 and high MnSOD expression being associated with lower 5-year survival rates and molecular subtypes with poorest prognosis. PMID- 26543229 TI - Colon cancer cell invasion is promoted by protein kinase CK2 through increase of endothelin-converting enzyme-1c protein stability. AB - Endothelin-converting enzyme-1c (ECE-1c) is a membrane metalloprotease involved in endothelin-1 synthesis, which has been shown in vitro to have a role in breast, ovary and prostate cancer cell invasion. N-terminal end of ECE-1c displays three putative phosphorylation sites for the protein kinase CK2. We studied whether CK2 phosphorylates N-terminal end of ECE-1c as well as whether this has a role in migration and invasion of colon cancer cells. CK2 phosphorylated the N-terminal end of ECE-1c and this was precluded upon inhibition of CK2. Inhibition also led to diminished protein levels of both endogen ECE-1 or GFP-fused N-terminal end of ECE-1c in 293T embryonic and DLD-1 colon cancer cells, which highlighted the importance of this motif on UPS dependent ECE-1c degradation. Full-length ECE-1c mutants designed either to mimic or abrogate CK2-phosphorylation displayed increased or decreased migration/invasion of colon cancer cells, respectively. Moreover, ECE-1c overexpression or its silencing with a siRNA led to increased or diminished cell migration/invasion, respectively. Altogether, these data show that CK2-increased ECE-1c protein stability is related to augmented migration and invasion of colon cancer cells, shedding light on a novel mechanism by which CK2 may promote malignant progression of this disease. PMID- 26543230 TI - Isothiocyanatostilbenes as novel c-Met inhibitors. AB - The hepatocyte growth factor receptor (HGFR or c-Met) is a driver of multiple cancer subtypes. While there are several c-Met inhibitors in development, few have been approved for clinical use, warranting the need for continued research and development of c-Met targeting therapeutic modalities. The research presented here demonstrates a particular class of compounds known as isothiocyanatostilbenes can act as c-Met inhibitors in multiple cancer cell lines. Specifically, we found that 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (H2DIDS) had c-Met inhibitory effective doses in the low micromolar range while 4 acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4' dinitrostilbene-2, 2'-disulfonic acid (DNDS) exhibited IC50s 100 to 1000 fold higher. These compounds displayed much greater selectivity for inhibiting c-Met activation compared to similar receptor tyrosine kinases. In addition, DIDS and H2DIDS reduced hepatocyte growth factor (HGF)-induced, but not epidermal growth factor (EGF)-induced, cell scattering, wound healing, and 3-dimensional (3D) proliferation of tumor cell spheroids. In-cell and cell-free assays suggested that DIDS and H2DIDS can inhibit and reverse c-Met phosphorylation, similar to SU11274. Additional data demonstrated that DIDS is tolerable in vivo. These data provide preliminary support for future studies examining DIDS, H2DIDS, and derivatives as potential c-Met therapeutics. PMID- 26543232 TI - miR-150 inhibits terminal erythroid proliferation and differentiation. AB - MicroRNAs (miRNAs), a class of small non-coding linear RNAs, have been shown to play a crucial role in erythropoiesis. To evaluate the indispensable role of constant suppression of miR-150 during terminal erythropoiesis, we performed miR 150 gain- and loss-of-function experiments on hemin-induced K562 cells and EPO induced human CD34+ cells. We found that forced expression of miR-150 suppresses commitment of hemoglobinization and CD235a labeling in both cell types. Erythroid proliferation is also inhibited via inducing apoptosis and blocking the cell cycle when miR-150 is overexpressed. In contrast, miR-150 inhibition promotes terminal erythropoiesis. 4.1 R gene is a new target of miR-150 during terminal erythropoiesis, and its abundance ensures the mechanical stability and deformability of the membrane. However, knockdown of 4.1 R did not affect terminal erythropoiesis. Transcriptional profiling identified more molecules involved in terminal erythroid dysregulation derived from miR-150 overexpression. These results shed light on the role of miR-150 during human terminal erythropoiesis. This is the first report highlighting the relationship between miRNA and membrane protein and enhancing our understanding of how miRNA works in the hematopoietic system. PMID- 26543233 TI - A functional variant in miR-155 regulation region contributes to lung cancer risk and survival. AB - Emerging evidence suggested that upregulation of miR-155 could serve as a promising marker for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). In the present study, we genotyped rs767649 (A > T) located in miR-155 regulation region in 1341 cases and 1982 controls, and analyzed the associations of rs767649 with NSCLC risk and survival. Consequently, rs767649 exhibited the significant associations with the risk (adjusted OR = 1.12, 95% CI = 1.01-1.24, P = 0.031) and prognosis of NSCLC (adjusted HR = 1.17, 95% CI = 1.03-1.32, P = 0.014). Meanwhile, rs767649 specifically interacted with radio-chemotherapy (P(int) = 0.013), and patients with both the rs767649-TT genotype and radio chemotherapy had the highest hazard ratio (adjusted HR = 1.65, 95% CI = 1.26 2.16, P < 0.001). Furthermore, using functional assays and The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) dataset, we found that rs767649 variant allele could increase the transcriptional activity of miR-155, which in turn facilitated tumor growth and metastasis by inhibiting HBP1, TJP1, SMAD5 and PRKAR1A expression. Our findings suggested that rs767649 A > T might contribute to the increased risk and poor prognosis of NSCLC, highlighting the importance of rs767649 in the prevention and therapy of NSCLC. PMID- 26543234 TI - Correlation of clinical features and genetic profiles of stromal interaction molecule 1 (STIM1) in colorectal cancers. AB - STIM1 overexpression has been observed in a portion of colorectal cancer (CRC) patients and associated with cancer cell invasion and migration. To characterize the distinctive expression profiles associated with stromal interaction molecule 1 (STIM1) overexpression/low-expression between CRC subtypes, and further assess the divergence transcription regulation impact of STIM1 between colon (COADs) and rectum (READs) adenocarcinomas in order to depict the role of SOCE pathway in CRCs, we have conducted a comprehensive phenome-transcriptome-interactome analysis to clarify underlying molecular differences of COADs/READs contributed by STIM1. Results demonstrated that a number of novel STIM1-associated signatures have been identified in COADs but not READs. Specifically, the presence of STIM1 overexpression in COADs, which represented a disturbance of the SOCE pathway, was associated with cell migration and cell motility properties. We identified 11 prognostic mRNA/miRNA predictors associated with the overall survival of COAD patients, suggesting the correlation of STIM1-associated features to clinicopathological outcomes. These findings enhance our understanding on differences between CRC subtypes in panoramic view, and suggested STIM1 as a promising therapeutic biomarker in COADs. PMID- 26543235 TI - Leptomeningeal metastasis in breast cancer - a systematic review. AB - BACKGROUND: There is limited data on the impact of specific patient characteristics, tumor subtypes or treatment interventions on survival in breast cancer LM. METHODS: A systematic review was conducted to assess the impact of hormone receptor and HER-2 status on survival in breast cancer LM. A search for clinical studies published between 1/1/2007 and 7/1/2012 and all randomized controlled trials was performed. Survival data from all studies are reported by study design (prospective trials, retrospective cohort studies, case studies). RESULTS: A total of 36 studies with 851 LM breast cancer subjects were identified. The majority (87%) were treated with intrathecal chemotherapy. Pooled median overall survival ranged from 14.9-18.1 weeks depending on study type. Breast cancer LM survival (15 weeks) was longer than other solid tumor LM 8.3 weeks and lung cancer LM 8.7 weeks, but shorter than LM lymphoma (15.4 versus 24.2 weeks). The impact of hormone receptor and HER-2 status on survival could not be determined. CONCLUSIONS: A median overall survival of 15 weeks in prospective studies of breast cancer LM provides a historical comparison for future LM breast cancer trials. Other outcomes including the impact of molecular status on survival could not be determined based on available studies. PMID- 26543236 TI - Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population. AB - More than 30 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer's disease (AD) risk by genome-wide association studies (GWAS) in European. We aimed to confirm these SNPs in Chinese Han and investigate the utility of these genetic markers. We randomly divided 459 sporadic AD (SAD) patients and 751 cognitively normal controls into two sets (discovery and testing). Thirty-three SAD risk-associated SNPs were firstly tested in the discovery set. Significant SNPs were used to calculate genetic risk score (GRS) in the testing set. Predictive performance of GRS was evaluated using the area under the receiver operating characteristic curve (AUC). In the discovery set, 6 SNPs were confirmed (P = 7.87 x 10(-11)~0.048), including rs9349407 in CD2AP, rs11218343 in SORL1, rs17125944 in FERMT2, rs6859 in PVRL2, rs157580 and rs2075650 in TOMM40. The first three SNPs were associated with SAD risk independent of APOE genotypes. GRS based on these three SNPs were significantly associated with SAD risk in the independent testing set (P = 0.002). The AUC for discriminating cases from controls was 0.58 for GRS, 0.60 for APOE, and 0.64 for GRS and APOE. Our data demonstrated that GRS based on AD risk-associated SNPs may supplement APOE for better assessing individual risk for AD in Chinese. PMID- 26543237 TI - Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation. AB - Glucose fermentation through glycolysis even in the presence of oxygen (Warburg effect) is a common feature of cancer cells increasingly considered as an enticing target in clinical development. This study aimed to analyze the link between metabolism, energy stores and proliferation rates in cancer cells. We found that cell proliferation, evaluated by DNA synthesis quantification, is correlated to glycolytic efficiency in six cancer cell lines as well as in isogenic cancer cell lines. To further investigate the link between glycolysis and proliferation, a pharmacological inhibitor of the pentose phosphate pathway (PPP) was used. We demonstrated that reduction of PPP activity decreases cancer cells proliferation, with a profound effect in Warburg-phenotype cancer cells. The crucial role of the PPP in sustaining cancer cells proliferation was confirmed using siRNAs against glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the PPP. In addition, we found that dichloroacetate (DCA), a new clinically tested compound, induced a switch of glycolytic cancer cells to a more oxidative phenotype and decreased proliferation. By demonstrating that DCA decreased the activity of the PPP, we provide a new mechanism by which DCA controls cancer cells proliferation. PMID- 26543238 TI - Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin. AB - Galectins are small soluble lectins that bind alpha-galactosides via their carbohydrate recognition domain (CRD). Their ability to dimerize is critical for the crosslinking of glycoprotein receptors and subsequent cellular signaling. This is particularly important in their immunomodulatory role via the induction of T-cell apoptosis. Because galectins play a central role in many pathologies, including cancer, they represent valuable therapeutic targets. At present, most inhibitors have been directed towards the CRD, a challenging task in terms of specificity given the high structural homology of the CRD among galectins. Such inhibitors are not effective at targeting CRD-independent functions of galectins. Here, we report a new class of galectin inhibitors that specifically binds human galectin-7 (hGal-7), disrupts the formation of homodimers, and inhibits the pro apoptotic activity of hGal-7 on Jurkat T cells. In addition to representing a new means to achieve specificity when targeting galectins, such inhibitors provide a promising alternative to more conventional galectin inhibitors that target the CRD with soluble glycans or other small molecular weight allosteric inhibitors. PMID- 26543239 TI - Probing non polar interstellar molecules through their protonated form: Detection of protonated cyanogen (NCCNH+). AB - Cyanogen (NCCN) is the simplest member of the series of dicyanopolyynes. It has been hypothesized that this family of molecules can be important constituents of interstellar and circumstellar media, although the lack of a permanent electric dipole moment prevents its detection through radioastronomical techniques. Here we present the first solid evidence of the presence of cyanogen in interstellar clouds through the detection of its protonated form toward the cold dark clouds TMC-1 and L483. Protonated cyanogen (NCCNH+) has been identified through the J = 5 - 4 and J = 10 - 9 rotational transitions using the 40m radiotelescope of Yebes and the IRAM 30m telescope. We derive beam averaged column densities for NCCNH+ of (8.6 +/- 4.4) * 1010 cm-2 in TMC-1 and (3.9 +/- 1.8) * 1010 cm-2 in L483, which translate to fairly low fractional abundances relative to H2, in the range (1-10) * 10-12. The chemistry of protonated molecules in dark clouds is discussed, and it is found that, in general terms, the abundance ratio between the protonated and non protonated forms of a molecule increases with increasing proton affinity. Our chemical model predicts an abundance ratio NCCNH+/NCCN of ~ 10-4, which implies that the abundance of cyanogen in dark clouds could be as high as (1-10) * 10-8 relative to H2, i.e., comparable to that of other abundant nitriles such as HCN, HNC, and HC3N. PMID- 26543240 TI - ACCURATE SPECTROSCOPIC CHARACTERIZATION OF OXIRANE: A VALUABLE ROUTE TO ITS IDENTIFICATION IN TITAN'S ATMOSPHERE AND THE ASSIGNMENT OF UNIDENTIFIED INFRARED BANDS. AB - In an effort to provide an accurate spectroscopic characterization of oxirane, state-of-the-art computational methods and approaches have been employed to determine highly accurate fundamental vibrational frequencies and rotational parameters. Available experimental data were used to assess the reliability of our computations, and an accuracy on average of 10 cm-1 for fundamental transitions as well as overtones and combination bands has been pointed out. Moving to rotational spectroscopy, relative discrepancies of 0.1%, 2%-3%, and 3% 4% were observed for rotational, quartic, and sextic centrifugal-distortion constants, respectively. We are therefore confident that the highly accurate spectroscopic data provided herein can be useful for identification of oxirane in Titan's atmosphere and the assignment of unidentified infrared bands. Since oxirane was already observed in the interstellar medium and some astronomical objects are characterized by very high D/H ratios, we also considered the accurate determination of the spectroscopic parameters for the mono-deuterated species, oxirane-d1. For the latter, an empirical scaling procedure allowed us to improve our computed data and to provide predictions for rotational transitions with a relative accuracy of about 0.02% (i.e., an uncertainty of about 40 MHz for a transition lying at 200 GHz). PMID- 26543241 TI - ACCURATE SPECTROSCOPIC CHARACTERIZATION OF PROTONATED OXIRANE: A POTENTIAL PREBIOTIC SPECIES IN TITAN'S ATMOSPHERE. AB - An accurate spectroscopic characterization of protonated oxirane has been carried out by means of state-of-the-art computational methods and approaches. The calculated spectroscopic parameters from our recent computational investigation of oxirane together with the corresponding experimental data available were used to assess the accuracy of our predicted rotational and IR spectra of protonated oxirane. We found an accuracy of about 10 cm-1 for vibrational transitions (fundamentals as well as overtones and combination bands) and, in relative terms, of 0.1% for rotational transitions. We are therefore confident that the spectroscopic data provided herein are a valuable support for the detection of protonated oxirane not only in Titan's atmosphere but also in the interstellar medium. PMID- 26543242 TI - Arthropod Surveillance Programs: Basic Components, Strategies, and Analysis. AB - Effective entomological surveillance planning stresses a careful consideration of methodology, trapping technologies, and analysis techniques. Herein, the basic principles and technological components of arthropod surveillance plans are described, as promoted in the symposium "Advancements in arthropod monitoring technology, techniques, and analysis" presented at the 58th annual meeting of the Entomological Society of America in San Diego, CA. Interdisciplinary examples of arthropod monitoring for urban, medical, and veterinary applications are reviewed. Arthropod surveillance consists of the three components: 1) sampling method, 2) trap technology, and 3) analysis technique. A sampling method consists of selecting the best device or collection technique for a specific location and sampling at the proper spatial distribution, optimal duration, and frequency to achieve the surveillance objective. Optimized sampling methods are discussed for several mosquito species (Diptera: Culicidae) and ticks (Acari: Ixodidae). The advantages and limitations of novel terrestrial and aerial insect traps, artificial pheromones and kairomones are presented for the capture of red flour beetle (Coleoptera: Tenebrionidae), small hive beetle (Coleoptera: Nitidulidae), bed bugs (Hemiptera: Cimicidae), and Culicoides (Diptera: Ceratopogonidae) respectively. After sampling, extrapolating real world population numbers from trap capture data are possible with the appropriate analysis techniques. Examples of this extrapolation and action thresholds are given for termites (Isoptera: Rhinotermitidae) and red flour beetles. PMID- 26543243 TI - An Accurate Timing Alignment Method with Time-to-Digital Converter Linearity Calibration for High-Resolution TOF PET. AB - Accurate PET system timing alignment minimizes the coincidence time window and therefore reduces random events and improves image quality. It is also critical for time-of-flight (TOF) image reconstruction. Here, we use a thin annular cylinder (shell) phantom filled with a radioactive source and located axially and centrally in a PET camera for the timing alignment of a TOF PET system. This timing alignment method involves measuring the time differences between the selected coincidence detector pairs, calibrating the differential and integral nonlinearity of the time-to-digital converter (TDC) with the same raw data and deriving the intrinsic time biases for each detector using an iterative algorithm. The raw time bias for each detector is downloaded to the front-end electronics and the residual fine time bias can be applied during the TOF list mode reconstruction. Our results showed that a timing alignment accuracy of better than +/-25 ps can be achieved, and a preliminary timing resolution of 473 ps (full width at half maximum) was measured in our prototype TOF PET/CT system. PMID- 26543244 TI - Effect of Non-Alignment/Alignment of Attenuation Map Without/With Emission Motion Correction in Cardiac SPECT/CT. AB - PURPOSE: We investigate the differences without/with respiratory motion correction in apparent imaging agent localization induced in reconstructed emission images when the attenuation maps used for attenuation correction (from CT) are misaligned with the patient anatomy during emission imaging due to differences in respiratory state. METHODS: We investigated use of attenuation maps acquired at different states of a 2 cm amplitude respiratory cycle (at end expiration, at end-inspiration, the center map, the average transmission map, and a large breath-hold beyond range of respiration during emission imaging) to correct for attenuation in MLEM reconstruction for several anatomical variants of the NCAT phantom which included both with and without non-rigid motion between heart and sub-diaphragmatic regions (such as liver, kidneys etc). We tested these cases with and without emission motion correction and attenuation map alignment/non-alignment. RESULTS: For the NCAT default male anatomy the false count-reduction due to breathing was largely removed upon emission motion correction for the large majority of the cases. Exceptions (for the default male) were for the cases when using the large-breathhold end-inspiration map (TI_EXT), when we used the end-expiration (TE) map, and to a smaller extent, the end inspiration map (TI). However moving the attenuation maps rigidly to align the heart region, reduced the remaining count-reduction artifacts. For the female patient count-reduction remained post motion correction using rigid map-alignment due to the breast soft-tissue misalignment. Quantitatively, after the transmission (rigid) alignment correction, the polar-map 17-segment RMS error with respect to the reference (motion-less case) reduced by 46.5% on average for the extreme breathhold case. The reductions were 40.8% for end-expiration map and 31.9% for end-inspiration cases on the average, comparable to the semi-ideal case where each state uses its own attenuation map for correction. CONCLUSIONS: Two main conclusions are that even rigid emission motion correction to rigidly align the heart region to the attenuation map helps in average cases to reduce the count-reduction artifacts and secondly, within the limits of the study (ex. rigid correction) when there is lung tissue inferior to the heart as with the NCAT phantom employed in this study endexpiration maps (TE) might best be avoided as they may create more artifacts than the end-inspiration (TI) maps. PMID- 26543245 TI - A Simple Low-dose X-ray CT Simulation from High-dose Scan. AB - Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID- 26543246 TI - From the Editor: The Journey to Open Access. PMID- 26543247 TI - Temperature Management Guidelines. PMID- 26543248 TI - The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass. AB - To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation. PMID- 26543249 TI - A Single-Center Analysis of Methylprednisolone Use during Pediatric Cardiopulmonary Bypass. AB - Cardiac surgery with the use of cardiopulmonary bypass (CPB) is known to induce an inflammatory response in patients. This response may be even more pronounced in pediatric patients given their small body size compared to adults. Several interventions have been instituted in an effort to attenuate this response, including the use of corticosteroids in the pump prime. However, the clinical effectiveness and potential harmful effects of steroid use have been the source of recent debate. Therefore, our institution made the decision to evaluate the use of methylprednisolone in our CPB prime. This evaluation was performed as a formal quality improvement project at The Children's Hospital of Philadelphia. Methylprednisolone was eliminated from the CPB prime for 6 months. At the end of this time period, The Society of Thoracic Surgeons Congenital Heart Surgery Database was used to evaluate clinical outcomes of patients (n = 222). These outcomes were then compared to patients operated on during the 6 months prior to elimination of methylprednisolone (n = 303). No significant clinical benefit was identified in the group of patients who received methylprednisolone. When compared to the group who did not receive methylprednisolone, significantly more patients in the steroids group had a postoperative wound infection (p = .037) or respiratory failure requiring tracheostomy ( p = .035). No other differences in clinical outcomes were identified between the two groups. No significant differences in clinical outcomes were identified between neonates who received methylprednisolone (n = 55) and neonates who did not receive steroids (n = 58). Due to the lack of clinical benefit seen with its use, as well as its potential contribution to the incidence of wound infection, methylprednisolone continues to be excluded from the CPB prime at our institution. Methylprednisolone is still given intraoperatively at the request of the attending anesthesiologist and on bypass during orthotopic transplant procedures according to institutional protocol. PMID- 26543250 TI - Vacuum-Assisted Venous Drainage: A 2014 Safety Survey. AB - Despite the widespread use of vacuum-assisted venous drainage (VAVD) and case reports describing catastrophic incidents related to VAVD, there is a lack of data cataloging specific safety measures that individuals and institutions have incorporated into their VAVD practices for the prevention of these incidents. Therefore, the purpose of this study is to survey the perfusion community to gather data on VAVD practices, and to compare these current practices with literature recommendations and the American Society of ExtraCorporeal Technology (AmSECT) Standards and Guidelines. In September 2014, a survey was distributed via PerfList and PerfMail, and by direct e-mail to members of the New York State Society of Perfusionists, targeting certified clinical perfusionists in New York State. Survey topics pertaining to VAVD practice included 1) equipment, 2) pressure monitoring and alarms, 3) protocols, checklists, and documentation, and 4) VAVD-related incidents. Of ~200 certified clinical perfusionists who live and/or work in New York State (NYS), 88 responded (42%). Most respondents (90.1%) report they use VAVD. Of these, 87.3% report that they monitor VAVD pressure, with 51.6% having audible and visual alarms for both positive and excessive negative pressures. At the institutional level, 61.2% of respondents reported that there is a protocol in place at for their team limiting negative pressure in the reservoir, 28.4% document VAVD pressure in the pump record, and AmSECT's three recommended VAVD checklist items are met with 53.7%, 55.1%, and 33.8% compliance. In conclusion, the results of this study reveal that the use of VAVD has increased and has become nearly universal in 2014. There is high compliance to some of the literature recommendations and AmSECT Standards and Guidelines, however, there are still some gaps between current practices and these recommendations. Continued improvement, both at the individual and institutional levels, will help to improve patient safety by preventing untoward events from occurring while using VAVD. PMID- 26543251 TI - Perioperative Hemoglobin Trajectory in Adult Cardiac Surgical Patients. AB - Preoperative anemia and nadir hemoglobin (Hb) during cardiopulmonary bypass (CPB) have been identified as significant risk factors for blood transfusion during cardiac surgery. The aim of this study was to confirm the association between preoperative anemia, perioperative fluid management, and blood transfusion. In addition, the proportion of elective cardiac surgery patients presenting for surgery with anemia was identified to examine whether the opportunity exists for timely diagnosis and intervention. Data from referral until hospital discharge were comprehensively reviewed over a 12-month period for all nonemergency cardiac surgical patients operated on in our institution. Of the 342 patients identified, elective cases were referred a median of 35 days before preoperative clinic and operated on a median of 14 days subsequently. Subacute cases had a median of 3 days from referral to surgery. As per the World Health Organization (WHO) criteria for anemia, 24.2% of elective and 29.6% of subacute patients were anemic. Blood transfusion was administered to 46.2% of patients during their admission. Transfusion was more likely in patients who were female (odds ratio [OR]: 2.45, 95%confidence interval [CI]: 1.28-4.70), had a low body mass index (BMI) (OR: .89, 95% CI: .84-.94), preoperative anemia (OR: 5.15, 95% CI: 2.59 10.24), or renal impairment (OR: 5.44, 95% CI: 2.42-12.22). Hemodilution minimization strategies reduced the Hb fall during CPB, but not transfusion rates. This study identifies a high prevalence of preoperative anemia with sufficient time for elective referrals to undergo appropriate diagnosis and interventions. It also confirms that low red cell mass (anemia and low BMI) and renal impairment are predictors of perioperative blood transfusion. Perfusion strategies to reduce hemodilution are effective at minimizing the intraoperative fall in Hb concentration but did not influence transfusion rate. PMID- 26543252 TI - Should Air Bubble Detectors Be Used to Quantify Microbubble Activity during Cardiopulmonary Bypass? AB - Air bubble detectors (ABDs) are utilized during cardiopulmonary bypass (CPB) to protect against massive air embolism. Stockert (Munich, Germany) ABD quantify microbubbles >300 MUm; however, their reliability has not been reported. The aim of this study was to assess the reliability of the microbubble data from the ABD with the SIII and S5 heart-lung machines. Microbubble counts from the ABD with the SIII (SIII ABD) and S5 (S5 ABD) were measured simultaneously with the emboli detection and classification (EDAC) quantifier in 12 CPB procedures using two EDAC detectors and two ABDs in series in the arterial line. Reliability was assessed by the Spearman correlation co-efficient (r) between measurements for each detector type, and between each ABD and EDAC detector for counts >300 MUm. No correlation was found between the SIII ABD (r = .008, p = .793). A weak negative correlation was found with the S5 ABD (r = -.16, p < .001). A strong correlation was found between the EDAC detectors (SIII; r = .958, p < .001), (S5; r = .908, p < .001). With counts >300 MUm, the SIII ABDs showed a correlation of small-medium effect size between EDAC detectors and ABD1 (r = .286, p < .001 [EDAC1], r = .347, p < .001 [EDAC2]). There was no correlation found between ABD2 and either EDAC detector (r = .003, p = .925 (EDAC1), r = .003, p = .929 [EDAC2]). A correlation between EDAC and the S5 ABD, was not able to be determined due to the low bubble count detected by the EDAC >300 MUm. Both SIII ABD and S5 ABD were found to be unreliable for quantification of microbubble activity during CPB in comparison with the EDAC. These results highlight the importance of ensuring that data included in the CPB report is accurate and clinically relevant, and suggests that microbubble counts from devices such as the SIII ABD and S5 ABD should not be reported. PMID- 26543253 TI - A Novel Method to Detect an Oxygenator Defect Prior to Cardiopulmonary Bypass Initiation. AB - Cardiopulmonary bypass (CPB) is a common practice in our era. The medical technology used for cardiac surgery goes through rigorous testing to ensure its safety. Unfortunately, it is not fail proof. Oxygenator failures are a rare occurrence but may lead to catastrophic events. We present a case where the preparation for initiating CPB was complicated by an oxygenator defect. After thorough examination, the oxygenator was found leaking from the gas exhaust port suggesting a disruption in continuity of the fibers. This was found by the vigilance of the perfusionist and a creative method to quickly assess the integrity of the oxygenation device. We describe a simple technique to help diagnose an oxygenator leak. PMID- 26543254 TI - Classic Pages of the Journal of Extracorporeal Technology: Does Perfusion Have a Safety Culture? PMID- 26543256 TI - Double Jeopardy? The Interaction of Gender and Race on Earnings in the U.S. AB - There are sizeable earnings differentials by both gender and race in the U.S. labor market, with women earning less than men and most racial/ethnic minority groups earning less than whites. It has been proposed in the previous literature that the effects of gender and race on earnings are additive, so that minority women suffer the full disadvantage of each status. We test this proposition for a broad range of minority groups in the U.S. We find that women of all minority groups in the U.S. suffer a smaller gender penalty than white women. Exploring the potential role of racial variation in gender role specialization in producing such differentials, we find some empirical evidence suggesting that white families specialize more than families of most other races. PMID- 26543255 TI - Home Remedy Use Among African American and White Older Adults. AB - Home remedy use is an often overlooked component of health self-management, with a rich tradition, particularly among African Americans and others who have experienced limited access to medical care or discrimination by the health care system. Home remedies can potentially interfere with biomedical treatments. This study documented the use of home remedies among older rural adults, and compared use by ethnicity (African American and white) and gender. A purposeful sample of 62 community-dwelling adults ages 65+ from rural North Carolina was selected. Each completed an in-depth interview, which probed current use of home remedies, including food and non-food remedies, and the symptoms or conditions for use. Systematic, computer-assisted analysis was used to identify usage patterns. Five food and five non-food remedies were used by a large proportion of older adults. African American elders reported greater use than white elders; women reported more use for a greater number of symptoms than men. Non-food remedies included long-available, over-the-counter remedies (e.g., Epsom salts) for which "offlabel" uses were reported. Use focused on alleviating common digestive, respiratory, skin, and musculoskeletal symptoms. Some were used for chronic conditions in lieu of prescription medications. Home remedy use continues to be a common feature of the health self-management of older adults, particularly among African Americans, though at lower levels than previously reported. While some use is likely helpful or benign, other use has the potential to interfere with medical management of disease. Health care providers should be aware of the use of remedies by their patients. PMID- 26543257 TI - Synthesis of cholesteryl-alpha-D-lactoside via generation and trapping of a stable beta-lactosyl iodide. AB - The generation of beta-lactosyl iodide was carried out under non-in situ anomerization, metal free conditions by reacting commercially available beta-per O-acetylated lactose with trimethylsilyl iodide (TMSI). The beta-iodide was surprisingly stable as evidenced by NMR spectroscopy. Introduction of octanol or cholesterol under microwave conditions gave high yields of alpha-linked glycoconjugates. Careful analysis of the reaction products and mechanistic considerations suggest an acid catalyzed rearrangement that provides alpha-linked glycosylation products with a free C2-hydroxyl. Accessibility to these compounds may further advance glycolipidomic profiling of immune modulating bacterial derived-glycans. PMID- 26543258 TI - 3,4- and 3,5-Disubstituted 2-Pyridones Using an Intermolecular Cycloaddition / Cycloreversion Strategy: Toward the Synthesis of Aristopyridinone A. AB - The intermolecular cycloaddition of pyrazinone precursors with alkyne substrates was evaluated. The resulting regioisomeric [2.2.2]-diketopiperazine alkene cycloadducts were diverted into 2-pyridone products through cycloreversion of the [2.2.2]-bicyclic intermediates. New insights into the regioselectivity of pyrazinone azadiene Diels-Alder reactions as well as cycloreversion reactivity were revealed in this study. Synthetic sequences using this [4+2]/r[4+2] strategy were determined that can produce predominantly the 3,5-disubstituted 2-pyridone alkaloid structures; pyridones featuring the 3,4-substitution pattern are observed as the minor regioisomeric products. PMID- 26543259 TI - Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks. AB - Streptococcus mutans, a Gram positive facultative anaerobe, is one among the approximately seven hundred bacterial species to exist in human buccal cavity and cause dental caries. Quorum sensing (QS) is a cell-density dependent communication process that respond to the inter/intra-species signals and elicit responses to show behavioral changes in the bacteria to an aggressive forms. In accordance to this phenomenon, the S. mutans also harbors a Competing Stimulating Peptide (CSP)-mediated quorum sensing, ComCDE (Two-component regulatory system) to regulate several virulence-associated traits that includes the formation of the oral biofilm (dental plaque), genetic competence and acidogenicity. The QS mediated response of S. mutans adherence on tooth surface (dental plaque) imparts antibiotic resistance to the bacterium and further progresses to lead a chronic state, known as periodontitis. In recent years, the oral streptococci, S. mutans are not only recognized for its cariogenic potential but also well known to worsen the infective endocarditis due to its inherent ability to colonize and form biofilm on heart valves. The review significantly appreciate the increasing complexity of the CSP-mediated quorum-sensing pathway with a special emphasis to identify the plausible drug targets within the system for the development of anti quorum drugs to control biofilm formation and associated risks. PMID- 26543260 TI - Thermus parvatiensis RL(T) sp. nov., Isolated from a Hot Water Spring, Located Atop the Himalayan Ranges at Manikaran, India. AB - A Gram negative, yellow pigmented, rod shaped bacterium designated as RL(T) was isolated from a hot water spring (90-98 degrees C) located at Manikaran in Northern India. The isolate grows at 60-80 degrees C (optimum, 70 degrees C) and at pH 7.0-9.0 (optimum pH 7.2). Phylogenetic analysis of 16S rRNA gene sequences and levels of DNA-DNA relatedness together indicate that the new isolate represents a novel species of the genus Thermus with closest affinity to Thermus thermophilus HB8(T) (99.5 %) followed by Thermus arciformis (96.4 %). A comparative analysis of partial sequences of housekeeping genes (HKG) further revealed that strain RL(T) is a novel species belonging to the genus Thermus. The melting G+C content of strain RL(T) was calculated as 68.7 mol%. The DNA-DNA relatedness value of strain RL(T) with its nearest neighbours (>97 %) was found to be less than 70 % indicating that strain RL(T) represents a novel species of the genus Thermus. MK-8 was the predominant respiratory quinone. The presence of characteristic phospholipid and glycolipid further confirmed that strain RL(T) belongs to the genus Thermus. The predominant fatty acids of strain RL(T) were iso-C17:0 (23.67 %) and iso-C15:0 (24.50 %). The results obtained after DNA-DNA hybridization, biochemical and physiological tests clearly distinguished strain RL(T) from its closely related species. Thus, strain RL(T) represents a novel species of the genus Thermus for which the name Thermus parvatiensis is proposed (=DSM 21745(T)= MTCC 8932(T)). PMID- 26543261 TI - Genome Wide Search for Biomarkers to Diagnose Yersinia Infections. AB - Bacterial identification on the basis of the highly conserved 16S rRNA (rrs) gene is limited by its presence in multiple copies and a very high level of similarity among them. The need is to look for other genes with unique characteristics to be used as biomarkers. Fifty-one sequenced genomes belonging to 10 different Yersinia species were used for searching genes common to all the genomes. Out of 304 common genes, 34 genes of sizes varying from 0.11 to 4.42 kb, were selected and subjected to in silico digestion with 10 different Restriction endonucleases (RE) (4-6 base cutters). Yersinia species have 6-7 copies of rrs per genome, which are difficult to distinguish by multiple sequence alignments or their RE digestion patterns. However, certain unique combinations of other common gene sequences-carB, fadJ, gluM, gltX, ileS, malE, nusA, ribD, and rlmL and their RE digestion patterns can be used as markers for identifying 21 strains belonging to 10 Yersinia species: Y. aldovae, Y. enterocolitica, Y. frederiksenii, Y. intermedia, Y. kristensenii, Y. pestis, Y. pseudotuberculosis, Y. rohdei, Y. ruckeri, and Y. similis. This approach can be applied for rapid diagnostic applications. PMID- 26543262 TI - Genome Wide Analysis for Rapid Identification of Vibrio Species. AB - The highly conserved 16S rRNA (rrs) gene is generally used for bacterial identification. In organisms possessing multiple copies of rrs, high intra genomic heterogeneity does not allow easy distinction among different species. In order to identify Vibrio species, a wide range of genes have been employed. There is an urgent requirement of a consensus gene, which can be used as biomarker for rapid identification. Eight sequenced genomes of Vibrio species were screened for selecting genes which were common among all the genomes. Out of 108 common genes, 24 genes of sizes varying from 0.11 to 3.94 kb were subjected to in silico digestion with 10 type II restriction endonucleases (RE). A few unique genes dapF, fadA, hisD, ilvH, lpxC, recF, recR, rph and ruvB in combination with certain REs provided unique digestion patterns, which can be used as biomarkers. This protocol can be exploited for rapid diagnosis of Vibrio species. PMID- 26543263 TI - Identification of Recombination and Positively Selected Genes in Brucella. AB - Brucella is a facultative intracellular bacterium belongs to the class alpha proteobacteria. It causes zoonotic disease brucellosis to wide range of animals. Brucella species are highly conserved in nucleotide level. Here, we employed a comparative genomics approach to examine the role of homologous recombination and positive selection in the evolution of Brucella. For the analysis, we have selected 19 complete genomes from 8 species of Brucella. Among the 1599 core genome predicted, 24 genes were showing signals of recombination but no significant breakpoint was found. The analysis revealed that recombination events are less frequent and the impact of recombination occurred is negligible on the evolution of Brucella. This leads to the view that Brucella is clonally evolved. On other hand, 56 genes (3.5 % of core genome) were showing signals of positive selection. Results suggest that natural selection plays an important role in the evolution of Brucella. Some of the genes that are responsible for the pathogenesis of Brucella were found positively selected, presumably due to their role in avoidance of the host immune system. PMID- 26543264 TI - Phylogenetic Profiling and Diversity of Bacterial Communities in the Death Valley, an Extreme Habitat in the Atacama Desert. AB - The Atacama Desert, one of the driest deserts in the world, represents a unique extreme environmental ecosystem to explore the bacterial diversity as it is considered to be at the dry limit for life. A 16S rRNA gene (spanning the hyper variable V3 region) library was constructed from an alkaline sample of unvegetated soil at the hyperarid margin in the Atacama Desert. A total of 244 clone sequences were used for MOTHUR analysis, which revealed 20 unique phylotypes or operational taxonomic units (OTUs). V3 region amplicons of the 16S rRNA were suitable for distinguishing the bacterial community to the genus and specie level. We found that all OTUs were affiliated with taxa representative of the Firmicutes phylum. The extremely high abundance of Firmicutes indicated that most bacteria in the soil were spore-forming survivors. In this study we detected a narrower diversity as compared to other ecological studies performed in other areas of the Atacama Desert. The reported genera were Oceanobacillus (representing the 69.5 % of the clones sequenced), Bacillus, Thalassobacillus and Virgibacillus. The present work shows physical and chemical parameters have a prominent impact on the microbial community structure. It constitutes an example of the communities adapted to live in extreme conditions caused by dryness and metal concentrations . PMID- 26543265 TI - Molecular Detection of New Delhi Metallo-Beta-Lactamase-1 (NDM-1) Positive Bacteria from Environmental and Drinking Water Samples by Loop Mediated Isothermal Amplification of bla NDM-1. AB - New Delhi metallo-beta-lactamase-1 gene (bla NDM-1 ) codes for New Delhi metallo beta-lactamase-1 (NDM-1) enzyme that cleaves the amide bond of beta-lactam ring, and provides resistance against major classes of beta-lactam antibiotics. Dissemination of the plasmid borne bla NDM-1 through horizontal gene transfer is a potential threat to the society. In this study, a rapid non-culture method for detecting NDM-1 positive bacteria was developed by Loop Mediated Isothermal Amplification (LAMP) of bla NDM-1 . Sensitivity of this method was found to be one femtogram of plasmid DNA, which translates into 2.6-25.8 copies depending on the size of the plasmid DNA. This method was applied to detect NDM-1 positive bacteria in 81 water samples that were collected from environmental and drinking water sources. NDM-1 positive bacteria were detected in three drinking water samples by LAMP but not by PCR. These three samples were collected from the water sources that were treated with chlorine for decontamination before public distribution. NDM-1 positive bacteria were not detected in lake water samples or in the samples that were collected from the water sources that were purified by reverse osmosis before public distribution. Detection of NDM-1 positive bacteria using LAMP was found to be safe, sensitive and rapid for screening large number of samples from diverse sources. This method could be developed as on-field detection kit by using fluorescent dyes to visualize the amplified bla NDM-1 gene. PMID- 26543266 TI - A Greenhouse Assay on the Effect of Applied Urea Amount on the Rhizospheric Soil Bacterial Communities. AB - The rhizospheric bacteria play key role in plant nutrition and growth promotion. The effects of increased nitrogen inputs on plant rhizospheric soils also have impacted on whole soil microbial communities. In this study, we analyzed the effects of applied nitrogen (urea) on rhizospheric bacterial composition and diversity in a greenhouse assay using the high-throughput sequencing technique. To explore the environmental factors driving the abundance, diversity and composition of soil bacterial communities, the relationship between soil variables and the bacterial communities were also analyzed using the mantel test as well as the redundancy analysis. The results revealed significant bacterial diversity changes at different amounts of applied urea, especially between the control treatment and the N fertilized treatments. Mantel tests showed that the bacterial communities were significantly correlated with the soil nitrate nitrogen, available nitrogen, soil pH, ammonium nitrogen and total organic carbon. The present study deepened the understanding about the rhizospheric soil microbial communities under different amounts of applied urea in greenhouse conditions, and our work revealed the environmental factors affecting the abundance, diversity and composition of rhizospheric bacterial communities. PMID- 26543267 TI - Bioconversion of Raw Glycerol Generated from the Synthesis of Biodiesel by Different Oleaginous Yeasts: Lipid Content and Fatty Acid Profile of Biomass. AB - In this work, 12 different yeast strains were evaluated to gauge their ability to accumulate lipids using raw glycerol as the main carbon source. Lipomyces lipofer NRRL Y-1155 stood out above the other strains, achieving 9.48 g/l biomass, 57.64 % lipid content and 5.46 g/l lipid production. The fatty acid profile was similar to vegetable oils commonly used in the synthesis of biodiesel, with the predominance of polyunsaturated acids, especially linoleic acid, reaching 68.3 % for Rhodotorula glutinis NRRL YB-252. The occurrence of palmitic acid (39.3 % for Lipomyces starkeyi NRRL Y-11557) was also notable. Thus, yeast biomass with high lipid content can be a sustainable and renewable alternative as a raw material for the biodiesel industry. PMID- 26543268 TI - Probiotic Strains Influence on Infant Microbiota in the In Vitro Colonic Fermentation Model GIS1. AB - The main goal of our study was to evaluate the effect of the individual administration of five lyophilized lactic acid bacteria strains (Lactobacillus fermentum 428ST, Lactobacillus rhamnosus E4.2, Lactobacillus plantarum FCA3, Lactobacillus sp. 34.1, Weissella paramesenteroides FT1a) against the in vitro simulated microbiota of the human colon using the GIS1 system. The influence on the metabolic activity was also assessed by quantitative determination of proteins and polysaccharides at each segment of human colon. The obtained results indicated that the lactic acid bacteria L. rhamnosus E4.2 and W. paramesenteroides FTa1 had better efficiency in synthesising exopolysaccharides and also a better probiotic potential and therefore could be recommended for use in probiotics products or food industry. PMID- 26543269 TI - Microbial Variants from Iron Ore Slimes: Mineral Specificity and pH Tolerance. AB - This paper describes the isolation of the native bacterial strains from the iron ore mines slime pond and its extremophilic characteristics. The two microbial isolates designated as CNIOS-1 and CNIOS-2 were grown in selective silicate broth at pH 7.0 and the organisms were tested for their selective adhesion on silicate and alumina minerals. The silicate bacteria with their exopolymers are very potent to grow over aluminosilicates. It was established that CNIOS-1 grew preferentially in the presence of silicate mineral compared to CNIOS-2 which grew in the presence of alumina. The organisms were tested for growth at various pH and trials were carried to define their efficacy for eventual applications to remove gangue minerals of silica and alumina from the raw material. PMID- 26543270 TI - Strain Improvement of Streptomyces xanthochromogenes RIA 1098 for Enhanced Pravastatin Production at High Compactin Concentrations. AB - Pravastatin is one of the most popular cholesterol-lowering drugs. Its industrial production represents a two-stage process including the microbial production of compactin and its further biocatalytic conversion to pravastatin. To increase a conversion rate, a higher compactin content in fermentation medium should be used; however, high compactin concentrations inhibit microbial growth. Therefore, the improvement of the compactin resistance of a producer still remains a relevant problem. A multi-step random UV mutagenesis of a Streptomyces xanthochromogenes strain RIA 1098 and the further selection of high-yield compactin-resistant mutants have resulted in a highly productive compactin resistant strain S 33-1. After the fermentation medium improvement, the maximum bioconversion rate of this strain has reached 91 % at the daily compactin dose equal to 1 g/L and still remained high (83 %) even at the doubled dose (2 g/L). A 1-year study of the mutant strain stability has proved a stable inheritance of its characteristics that provides this strain to be very promising for the pravastatin-producing industry. PMID- 26543271 TI - Improvement in Oil Production by Increasing Malonyl-CoA and Glycerol-3-Phosphate Pools in Scenedesmus quadricauda. AB - In recent years, microalgae have attracted considerable interest as a biofuel resource owing to their rapid growth, tolerance to harsh conditions, and ability to accumulate a large amount of triacylglycerols (TAGs). However, the economic effectiveness of algal biofuel is still low. In this study, we attempted to increase oil production of the microalga Scenedesmus quadricauda by elevating intracellular malonyl-CoA and glycerol-3-phosphate (G3P) pools. To increase intracellular oil content, yeast-derived genes encoding acetyl-CoA carboxylase (ACC1), glycerol kinase (GPD1), and glycerol-3-phosphate dehydrogenase (GUT1) were overexpressed under the control of CaMV 35S and NOS promoters with SV40 large T antigen components. Fatty acid profiling, G3P content, and the number of cells with high oil content were analyzed by gas chromatography-mass spectrometry, G3P assay kit, and flow cytometry, respectively. Overexpression of ACC1 increased the total fatty acid content by 1.6-fold. Overexpression of GPD1 and GUT1 increased intracellular G3P content by 1.6- and 1.9-fold, respectively. Multi-gene expression of ACC1, GPD1, and GUT1 increased the number of cells with high oil content by 1.45-fold compared with that observed with the wild-type. This study is the first to report increased oil production by overexpression of the key genes (ACC1, GPD1, and GUT1) for TAG biosynthesis in microalgae. PMID- 26543272 TI - The Tussle Between Mycobacteria and Host: To Eat or Not To Eat. AB - Autophagy is a catabolic process of cellular homeostasis evolutionarily conserved in eukaryotes. To block infection of intracellular bacterial pathogens, metazoans deploy autophagy for pathogen clearance through phago-lysosome formation and specific bactericidal peptides. Although an array of research have publicized the host regulatory factors, the function of bacterial effectors are yet to be understood in detail. In this article, we focus on the autophagic response to one of the most successful intracellular bacteria Mycobacterium tuberculosis. PMID- 26543273 TI - A Method for Cell Culture and Maintenance of Ammonia-Oxidizing Archaea in Agar Stab. AB - Ammonia oxidizing archaea (AOA) are predominantly found and closely linked with geochemical cycling of nitrogen in non-extreme habitats. However, these strains have mainly been investigated using liquid cultures of enriched cells. Here, we provide an agar stab as a simple and reliable means of cultivating and maintaining AOA. PMID- 26543274 TI - The Incidence of Non-tuberculous Mycobacterium Lung Disease in Patients with Suspected Pulmonary Tuberculosis. AB - Non-tuberculous mycobacterium (NTM) lung disease is increasing in prevalence. We analyzed the frequency of NTM lung disease among patients who are suspected of tuberculosis. NTM was isolated from about one-fourth of the mycobacterium culture positive patients and about half of these had NTM lung disease. Therefore, NTM isolates should be routinely identified at the species level for adequate treatment. PMID- 26543275 TI - The Fine-Gray Model Under Interval Censored Competing Risks Data. AB - We consider semiparametric analysis of competing risks data subject to mixed case interval censoring. The Fine-Gray model (Fine & Gray, 1999) is used to model the cumulative incidence function and is coupled with sieve semiparametric maximum likelihood estimation based on univariate or multivariate likelihood. The univariate likelihood of cause-specific data enables separate estimation of cumulative incidence function for each competing risk, in contrast with the multivariate likelihood of full data which estimates cumulative incidence functions for multiple competing risks jointly. Under both likelihoods and certain regularity conditions, we show that the regression parameter estimator is asymptotically normal and semiparametrically efficient, although the spline-based sieve estimator of the baseline cumulative subdistribution hazard converges at a rate slower than root-n. The proposed method is evaluated by simulation studies regarding its finite sample performance and is illustrated by a competing risk analysis of data from an dementia cohort study. PMID- 26543277 TI - Radiological findings of pulmonary tuberculosis in indigenous patients in Dourados, MS, Brazil. AB - OBJECTIVE: To describe the radiological findings of pulmonary tuberculosis in indigenous patients from the city of Dourados, MS, Brazil, according to age and sex. MATERIALS AND METHODS: Chest radiographic images of 81 patients with pulmonary tuberculosis, acquired in the period from 2007 to 2010, were retrospectively analyzed by two radiologists in consensus for the presence or absence of changes. The findings in abnormal radiographs were classified according to the changes observed and they were correlated to age and sex. The data were submitted to statistical analysis. RESULTS: The individuals' ages ranged from 1 to 97 years (mean: 36 years). Heterogeneous consolidations, nodules, pleural involvement and cavities were the most frequent imaging findings. Most patients (55/81 or 67.9%) were male, and upper lung and right lung were the most affected regions. Fibrosis, heterogeneous consolidations and involvement of the left lung apex were significantly more frequent in males (p < 0.05). Presence of a single type of finding at radiography was most frequent in children (p < 0.05). CONCLUSION: Based on the hypothesis that indigenous patients represent a population without genetically determined resistance to tuberculosis, the present study may enhance the knowledge about how the pulmonary form of this disease manifests in susceptible individuals. PMID- 26543276 TI - Indexical properties influence time-varying amplitude and fundamental frequency contributions of vowels to sentence intelligibility. AB - The present study investigated how non-linguistic, indexical information about talker identity interacts with contributions to sentence intelligibility by the time-varying amplitude (temporal envelope) and fundamental frequency (F0). Young normal-hearing adults listened to sentences that preserved the original consonants but replaced the vowels with a single vowel production. This replacement vowel selectively preserved amplitude or F0 cues of the original vowel, but replaced cues to phonetic identity. Original vowel duration was always preserved. Three experiments investigated indexical contributions by replacing vowels with productions from the same or different talker, or by acoustically morphing the original vowel. These stimulus conditions investigated how vowel suprasegmental and indexical properties interact and contribute to intelligibility independently from phonetic information. Results demonstrated that indexical properties influence the relative contribution of suprasegmental properties to sentence intelligibility. F0 variations are particularly important in the presence of conflicting indexical information. Temporal envelope modulations significantly improve sentence intelligibility, but are enhanced when either indexical or F0 cues are available. These findings suggest that F0 and other indexical cues may facilitate perceptually grouping suprasegmental properties of vowels with the remainder of the sentence. Temporal envelope modulations of vowels may contribute to intelligibility once they are successfully integrated with the preserved signal. PMID- 26543279 TI - Sonographic diagnosis of carpal tunnel syndrome: a study in 200 hospital workers. AB - OBJECTIVE: To describe the prevalence of carpal tunnel syndrome in a sample of 200 healthy hospital workers, establishing the respective epidemiological associations. MATERIALS AND METHODS: Two hundred individuals were submitted to wrist ultrasonography to measure the median nerve area. They were questioned and examined for epidemiological data, body mass index, carpal tunnel syndrome signs and symptoms, and submitted to the Boston carpal tunnel questionnaire (BCTQ) to evaluate the carpal tunnel syndrome severity. A median nerve area >= 9 mm(2) was considered to be diagnostic of carpal tunnel syndrome. RESULTS: Carpal tunnel syndrome was diagnosed by ultrasonography in 34% of the sample. It was observed the association of carpal tunnel syndrome with age (p < 0.0001), paresthesia (p < 0.0001), Tinel's test (p < 0.0001), Phalen's test (p < 0.0001), BCTQ score (p < 0.0001), and years of formal education (p < 0.0001). Years of formal education was the only variable identified as an independent risk factor for carpal tunnel syndrome (95% CI = 1.03 to 1.24). CONCLUSION: The prevalence of carpal tunnel syndrome in a population of hospital workers was of 34%. The number of years of formal education was the only independent risk factor for carpal tunnel syndrome. PMID- 26543278 TI - Rotational assessment of distal femur and its relevance in total knee arthroplasty: analysis by magnetic resonance imaging. AB - OBJECTIVE: To define the distal femur rotation pattern in a Brazilian population, correlating such pattern with the one suggested by the arthroplasty instruments, and analyzing the variability of each anatomic parameter. MATERIALS AND METHODS: A series of 101 magnetic resonance imaging studies were evaluated in the period between April and June 2012. The epidemiological data collection was performed with the aid of the institution's computed imaging system, and the sample included 52 male and 49 female patients. The measurements were made in the axial plane, with subsequent correlation and triangulation with the other plans. The posterior condylar line was used as a reference for angle measurements. Subsequently, the anatomical and surgical transepicondylar axes and the anteroposterior trochlear line were specified. The angles between the reference line and the studied lines were calculated with the aid of the institution's software. RESULTS: The mean angle between the anatomical transepicondylar axis and the posterior condylar line was found to be 6.89 degrees , ranging from 0.25 degrees to 12 degrees . For the surgical transepicondylar axis, the mean value was 2.89 degrees , ranging from -2.23 degrees (internal rotation) to 7.86 degrees , and for the axis perpendicular to the anteroposterior trochlear line, the mean value was 4.77 degrees , ranging from -2.09 degrees to 12.2 degrees . CONCLUSION: The anatomical transepicondylar angle showed mean values corresponding to the measurement observed in the Caucasian population. The utilized instruments are appropriate, but no anatomical parameter proved to be steady enough to be used in isolation. PMID- 26543280 TI - Readjustment of abdominal computed tomography protocols in a university hospital: impact on radiation dose. AB - OBJECTIVE: To assess the reduction of estimated radiation dose in abdominal computed tomography following the implementation of new scan protocols on the basis of clinical suspicion and of adjusted images acquisition parameters. MATERIALS AND METHODS: Retrospective and prospective review of reports on radiation dose from abdominal CT scans performed three months before (group A - 551 studies) and three months after (group B - 788 studies) implementation of new scan protocols proposed as a function of clinical indications. Also, the images acquisition parameters were adjusted to reduce the radiation dose at each scan phase. The groups were compared for mean number of acquisition phases, mean CTDIvol per phase, mean DLP per phase, and mean DLP per scan. RESULTS: A significant reduction was observed for group B as regards all the analyzed aspects, as follows: 33.9%, 25.0%, 27.0% and 52.5%, respectively for number of acquisition phases, CTDIvol per phase, DLP per phase and DLP per scan (p < 0.001). CONCLUSION: The rational use of abdominal computed tomography scan phases based on the clinical suspicion in conjunction with the adjusted images acquisition parameters allows for a 50% reduction in the radiation dose from abdominal computed tomography scans. PMID- 26543281 TI - Solutions in radiology services management: a literature review. AB - OBJECTIVE: The present study was aimed at reviewing the literature to identify solutions for problems observed in radiology services. MATERIALS AND METHODS: Basic, qualitative, exploratory literature review at Scopus and SciELO databases, utilizing the Mendeley and Illustrator CC Adobe softwares. RESULTS: In the databases, 565 papers - 120 out of them, pdf free - were identified. Problems observed in the radiology sector are related to procedures scheduling, humanization, lack of training, poor knowledge and use of management techniques, and interaction with users. The design management provides the services with interesting solutions such as Benchmarking, CRM, Lean Approach, ServiceBlueprinting, continued education, among others. CONCLUSION: Literature review is an important tool to identify problems and respective solutions. However, considering the small number of studies approaching management of radiology services, this is a great field of research for the development of deeper studies. PMID- 26543282 TI - Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach. AB - OBJECTIVE: The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients' body mass index. MATERIALS AND METHODS: The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality. RESULTS: An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes. CONCLUSION: The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient. PMID- 26543283 TI - Inflammatory pseudotumor of the hip: a complication of arthroplasty to be recognized by the radiologist. AB - Soft tissue complications following hip arthroplasty may occur either in cases of total hip arthroplasty or in hip resurfacing, a technique that has become popular in cases involving young patients. Both orthopedic and radiological literatures are now calling attention to these symptomatic periprosthetic soft tissue masses called inflammatory pseudotumors or aseptic lymphocytic vasculites-associated lesions. Pseudotumors are associated with pain, instability, neuropathy, and premature loosening of prosthetic components, frequently requiring early and difficult reoperation. Magnetic resonance imaging plays a relevant role in the evaluation of soft tissue changes in the painful hip after arthroplasty, ranging from early periprosthetic fluid collections to necrosis and more extensive tissue damage. PMID- 26543284 TI - Ultrasound scan as a potential source of nosocomial and crossinfection: a literature review. AB - The authors review the main concepts regarding the importance of cleaning/disinfection of ultrasonography probes, aiming a better comprehension by practitioners and thus enabling strategies to establish a safe practice without compromising the quality of the examination and the operator productivity. In the context of biosafety, it is imperative to assume that contact with blood or body fluids represents a potential source of infection. Thus, in order to implement cleaning/disinfection practice, it is necessary to understand the principles of infection control, to consider the cost/benefit ratio of the measures to be implemented, and most importantly, to comprehend that such measures will not only benefit the health professional and the patient, but the society as a whole. PMID- 26543285 TI - Study of the skin anatomy with high-frequency (22 MHz) ultrasonography and histological correlation. AB - The present essay is aimed at getting the radiologist familiar with the basic histological skin structure, allowing for a better correlation with sonographic findings. A high-frequency (22 MHz) ultrasonography apparatus was utilized in the present study. The histological analysis was performed after the skin specimens fixation with formalin, inclusion in paraffin blocks and subsequent staining with hematoxylin-eosin. The authors present a literature review showing the relationship between sonographic and histological findings in normal cutaneous tissue, and discuss the technique for a better performance of the sonographic scan. High-frequency ultrasonography is an excellent tool for the diagnosis of different skin conditions. However, as this method is operator-dependent, it is crucial to understand the normal skin structure as well as the correlation between histological and sonographic findings. PMID- 26543286 TI - Spontaneous rupture of ovarian cystadenocarcinoma: pre- and post-rupture computed tomography evaluation. AB - Epithelial ovarian tumors are the most common malignant ovarian neoplasms and, in most cases, eventual rupture of such tumors is associated with a surgical procedure. The authors report the case of a 54-year-old woman who presented with spontaneous rupture of ovarian cystadenocarcinoma documented by computed tomography, both before and after the event. In such cases, a post-rupture staging tends to be less favorable, compromising the prognosis. PMID- 26543287 TI - Pulmonary artery sarcoma mimicking chronic pulmonary thromboembolism. PMID- 26543288 TI - Central nervous system involvement in sarcoidosis. PMID- 26543289 TI - Femoral artery injury during aneurysm coiling. PMID- 26543291 TI - Chordoid glioma of the third ventricle. PMID- 26543290 TI - Primary intercavernous lymphoma of the central nervous system. PMID- 26543292 TI - Enteroenteric intussusception in an adult caused by an ileal angiomyolipoma. PMID- 26543293 TI - Diagnosis of pulmonary alveolar microlithiasis. PMID- 26543294 TI - Pulmonary tuberculosis in Brazilian indians: a picture of this context depicted through radiography. PMID- 26543295 TI - Magnetic resonance imaging in the assessment of hip arthroplasty complications. PMID- 26543296 TI - A comparison of 2D and 3D digital image correlation for a membrane under inflation. AB - Three-dimensional (3D) digital image correlation (DIC) is becoming widely used to characterize the behavior of structures undergoing 3D deformations. However, the use of 3D-DIC can be challenging under certain conditions, such as high magnification, and therefore small depth of field, or a highly controlled environment with limited access for two-angled cameras. The purpose of this study is to compare 2D-DIC and 3D-DIC for the same inflation experiment and evaluate whether 2D-DIC can be used when conditions discourage the use of a stereo-vision system. A latex membrane was inflated vertically to 5.41 kPa (reference pressure), then to 7.87 kPa (deformed pressure). A two-camera stereo-vision system acquired top-down images of the membrane, while a single camera system simultaneously recorded images of the membrane in profile. 2D-DIC and 3D-DIC were used to calculate horizontal (in the membrane plane) and vertical (out of the membrane plane) displacements, and meridional strain. Under static conditions, the baseline uncertainty in horizontal displacement and strain were smaller for 3D-DIC than 2D-DIC. However, the opposite was observed for the vertical displacement, for which 2D-DIC had a smaller baseline uncertainty. The baseline absolute error in vertical displacement and strain were similar for both DIC methods, but it was larger for 2D-DIC than 3D-DIC for the horizontal displacement. Under inflation, the variability in the measurements were larger than under static conditions for both DIC methods. 2D-DIC showed a smaller variability in displacements than 3D-DIC, especially for the vertical displacement, but a similar strain uncertainty. The absolute difference in the average displacements and strain between 3D-DIC and 2D-DIC were in the range of the 3D-DIC variability. Those findings suggest that 2D-DIC might be used as an alternative to 3D-DIC to study the inflation response of materials under certain conditions. PMID- 26543297 TI - The effects of vibration-reducing gloves on finger vibration. AB - : Vibration-reducing (VR) gloves have been used to reduce the hand-transmitted vibration exposures from machines and powered hand tools but their effectiveness remains unclear, especially for finger protection. The objectives of this study are to determine whether VR gloves can attenuate the vibration transmitted to the fingers and to enhance the understanding of the mechanisms of how these gloves work. Seven adult male subjects participated in the experiment. The fixed factors evaluated include hand force (four levels), glove condition (gel-filled, air bladder, no gloves), and location of the finger vibration measurement. A 3-D laser vibrometer was used to measure the vibrations on the fingers with and without wearing a glove on a 3-D hand-arm vibration test system. This study finds that the effect of VR gloves on the finger vibration depends on not only the gloves but also their influence on the distribution of the finger contact stiffness and the grip effort. As a result, the gloves increase the vibration in the fingertip area but marginally reduce the vibration in the proximal area at some frequencies below 100 Hz. On average, the gloves reduce the vibration of the entire fingers by less than 3% at frequencies below 80 Hz but increase at frequencies from 80 to 400 Hz. At higher frequencies, the gel-filled glove is more effective at reducing the finger vibration than the air bladder-filled glove. The implications of these findings are discussed. RELEVANCE TO INDUSTRY: Prolonged, intensive exposure to hand-transmitted vibration can cause hand-arm vibration syndrome. Vibration-reducing gloves have been used as an alternative approach to reduce the vibration exposure. However, their effectiveness for reducing finger-transmitted vibrations remains unclear. This study enhanced the understanding of the glove effects on finger vibration and provided useful information on the effectiveness of typical VR gloves at reducing the vibration transmitted to the fingers. The new results and knowledge can be used to help select appropriate gloves for the operations of powered hand tools, to help perform risk assessment of the vibration exposure, and to help design better VR gloves. PMID- 26543298 TI - Higher-Order Mentalising and Executive Functioning. AB - Higher-order mentalising is the ability to represent the beliefs and desires of other people at multiple, iterated levels - a capacity that sets humans apart from other species. However, there has not yet been a systematic attempt to determine what cognitive processes underlie this ability. Here we present three correlational studies assessing the extent to which performance on higher-order mentalising tasks relates to emotion recognition, self-reported empathy and self inhibition. In Study 1a and 1b, examining emotion recognition and empathy, a relationship was identified between individual differences in the ability to mentalise and an emotion recognition task (the Reading the Mind in the Eyes task), but no correlation was found with the Empathy Quotient, a self-report scale of empathy. Study 2 investigated whether a relationship exists between individual mentalising abilities and four different forms of self-inhibition: motor inhibition, executive inhibition, automatic imitation and temporal discounting. Results demonstrate that only temporal discounting performance relates to mentalising ability; suggesting that cognitive skills relevant to representation of the minds of others' are not influenced by the ability to perform more basic inhibition. Higher-order mentalising appears to rely on the cognitive architecture that serves both low-level social cognition (emotion recognition), and complex forms of inhibition. PMID- 26543299 TI - CD73 Predicts Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer. AB - AIMS: CD73 is a membrane associated 5'-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course. METHODS: Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray. Associations between CD73 expression and retrospectively obtained clinicopathological data were evaluated by contingency analysis. Survival analysis was performed to investigate the predictive value of CD73 within the subgroup of pTa and pT1 tumors in regard to progression-free survival (PFS). RESULTS: High CD73 expression was found in 46 (26.4%) patients and was significantly associated with lower stage, lower grade, less adjacent carcinoma in situ and with lower Ki-67 proliferation index. High CD73 immunoreactivity in the subgroup of pTa and pT1 tumors (n = 158) was significantly associated with longer PFS (HR: 0.228; p = 0.047) in univariable Cox regression analysis. CONCLUSION: High CD73 immunoreactivity was associated with favorable clinicopathological features. Furthermore, it predicts better outcome in the subgroup of pTa and pT1 tumors and may thus serve as additional tool for the selection of patients with favorable prognosis. PMID- 26543301 TI - Energy Saving in Office Buildings: Are Feedback and Commitment-Making Useful Instruments to Trigger Change? AB - This study focuses on energy saving in an office environment. We developed and tested an intervention that contained both the administration of feedback as well as commitment-making: two techniques that are often described in the literature as successful, especially when combined. Using a sample of 146 employees, we tested the intervention's effectiveness for our sample in terms of behavior change. Our results show some effects, but these were irrespective of experimental category. We use this failed experiment to reflect upon critical aspects of the design and implementation of intervention, and provide ideas on how such interventions can be improved. PMID- 26543300 TI - Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk. AB - Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol related liver disease. However, GGT's predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF) levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep. GGT is an early predictive marker for atherosclerosis, heart failure, arterial stiffness and plaque, gestational diabetes, and various liver diseases, including viral hepatitis, other infectious diseases, and several life-threatening cancers. We review literature both from the medical sciences and from life insurance industries demonstrating that serum GGT is a superior marker for future disease risk, when compared against multiple other known mortality risk factors. PMID- 26543302 TI - Oil Extraction and Indigenous Livelihoods in the Northern Ecuadorian Amazon. AB - Globally, the extraction of minerals and fossil fuels is increasingly penetrating into isolated regions inhabited by indigenous peoples, potentially undermining their livelihoods and well-being. To provide new insight to this issue, we draw on a unique longitudinal dataset collected in the Ecuadorian Amazon over an 11 year period from 484 indigenous households with varying degrees of exposure to oil extraction. Fixed and random effects regression models of the consequences of oil activities for livelihood outcomes reveal mixed and multidimensional effects. These results challenge common assumptions about these processes and are only partly consistent with hypotheses drawn from the Dutch disease literature. PMID- 26543303 TI - In Vitro Evaluation of Achillea Millefolium on the Production and Stimulation of Human Skin Fibroblast Cells (HFS-PI-16). AB - AIM: In the present study, we aimed the effects of the hydroalcoholic extract of Achillea millefolium (HEAML) on human skin fibroblast cells (HSF-PI-16) proliferation, stimulation and growth properties. METHODS: Initially, using HSF PI-16 monolayer culture, we created one line scratch method as an in vitro wound closure and after 3 days monitored via an inverted microscopy. RESULTS: HEAML selectively inhibited proliferation of HSF-PI-16 cells at higher concentration (>20.0 mg/mL), and stimulated at lower concentrations (<20.0 mg/mL). Following, HSF-PI-16 media treatments up to 72 h, HEAML demonstrated significantly elevated proliferation rates (p<0.05) and stimulation in a scratch wound assay (p<0.04). Furthermore, the morphological analysis of HSF-PI-16 cells at culture media were detected the figures of round to spindle, non-adherent, immature and mature cells. CONCLUSION: These results clearly demonstrate the absence of any toxic effect of HEAML on human skin fibroblasts. To the best of our knowledge, this is the first report elucidating potential mechanisms of action of HEAML on fibroblasts proliferation, and stimulation, offering a greater insight and a better understanding of its effect in future studies. PMID- 26543304 TI - Quality and Safety of General Anesthesia with Propofol and Sevoflurane in Children Aged 1-14 Based on Laboratory Parameters. AB - INTRODUCTION: Knowledge of anatomic, physiological, biochemical and physical characteristics of children of all age groups, the existing illness and possible pathological response of the organism to the existing situation, require a pediatric anesthesiologist to participate in the preparation of a child for surgical treatment, to choose the best anesthesia technique and medications, and manipulative techniques to enable the scheduled surgical treatment with minimum anesthesia risks. The aim of this clinical study was to prove reliability and quality of propofol or sevoflurane general anesthesia in children in the age group of 1-14 years from the ASA I group and in the elective surgical treatments in duration of 60 minutes, based on preoperative and postoperative levels of laboratory findings (transaminases, blood sugar, urea and creatinine). MATERIALS AND METHODS: the study included 160 patients randomized in two groups based on different approaches: total intravenous anesthesia was used for the propofol group (n=80) (TIVA) and the inhalation technique was used for the sevoflurane group (n=80). RESULTS: statistical evaluation of the obtained results indicates stability of laboratory findings in the immediate postoperative course (after 24 hours) in respect to the preoperative period. Based on the Mann Whitney test (P), preoperative and postoperative blood sugar levels in the sevoflurane vs. propofol group were P=0.152 vs. 0.021; creatinine levels P=0.113 vs. 0.325; urea levels P= 0.016 vs. 0.900; AST levels P=0,031 vs. 0,268 and ALT levels P=0.021 vs. 0.058. Level of significance was P<0.5. CONCLUSION: Analysis of the examined laboratory parameters show that propofol and sevoflurane provide full security and quality of general anesthesia in children age group 1-14 years, from the ASA I group. All analyzed laboratory levels in the postoperative course remained in their referential values in both groups of participants. PMID- 26543305 TI - Analysis of Cystic Fibrosis in Federation of Bosnia and Herzegovina. AB - AIM: The aim of this study is to present the first total number of tested children in the Federation of Bosnia and Herzegovina and the number of children with positive sweat test. During the study we determined the number of ill children, the median age of children with cystic fibrosis, date of initial diagnosis, an average amount of chloride in the sweat. MATERIAL AND METHODS: The study was a retrospective, conducted at the Department of Pulmonology Pediatric Clinic of University Clinical Center of Sarajevo. RESULTS: In the period from March 2003 to December 2014, we have tested 625 children. 351 child were from Sarajevo Canton and 272 children from other cantons. Female children were more affected then male children, in the ratio of 1: 1,105. An average age of female children was 4.19+/-4.26 years, and the male 2.15+/-3.11 years. The median concentration of chloride in the sweat measured by sweat test was for male children 103.05+/-21.29 mmol/L, and for the female children 96.05+/-28.85 mmol/L. CONCLUSION: Most of children in Federation of Bosnia and Herzegovina have ?F508 gene mutation. In the post-war period we started to use a sweat test. Male children tend to live longer than female children with CF. PMID- 26543306 TI - Hypoglycemia in Non-diabetics During Development of Acute Coronary Ischemia. AB - INTRODUCTION: The occurrence of hyperglycemia in non-diabetics during development of acute coronary ischemia (ACI) indicates latent glucose metabolism disorder, or is a case of newly discovered diabetes mellitus (DM) as a result of stress. Acute coronary syndrome refers to a group of clinical syndromes caused by a sudden circulatory disorder in coronary arteries, resulting in the corresponding myocardial ischemia. It covers range from unstable angina and myocardial infarction (MI) without Q wave in the electrocardiogram finding (NSTEMI) up to myocardial infarction with Q wave in the electrocardiogram finding (STEMI). GOAL: To determine the incidence of hyperglycemia in non-diabetics immediately after the occurrence of acute coronary ischemia and assess its risk factors. RESULTS: The sample included 80 respondents. Men dominated with a total prevalence of 77.5%. The respondent was at mean age of 62.8+/-13.8 years. During the first measurement, immediately after hospital admission, 50% of respondents had increased blood glucose value and during the second measurement 62%. Hypertension as a risk factor has 54% and 56% smoking. The incidence of stress diabetes after ACI does not depend on the diagnosis of hypertension, chi(2)=0.050; p=0.823. The differences of mean values (median) BMI between examined persons with/without stress DM are not statistically significant p=0.402. Independent t-test showed that there was no statistically significant difference in the average values of HDL and LDL in patients with stress diabetes than in patients without diabetes stress after ACI p>0.05. For each year of age odds ratio for "stress diabetes" increases by 7% and 95% CI is 2% -12%. CONCLUSION: The incidence of stress diabetes ACI is not dependent on the working diagnosis (MI or angina pectoris). As risk factors we set hypertension and current smoking. There were no statistically significant associations between active smoking and hypertension as a risk factor in relation to occurrence of stress diabetes. PMID- 26543307 TI - The Antioxidative Effect of Chamomile, Anthocyanoside and their Combination on Bleomycin-induced Pulmonary Fibrosis in Rat. AB - INTRODUCTION: Bleomycin is a small peptide with 1500Daltun of molecular weight which has two junction areas in two molecule's opposite sides, one of them to relate to the DNA and the other to relate to the iron. Iron is a crucially important factor in free radical production and cytotoxic activity of bleomycin. MATERIAL AND METHODS: The study attempts to study, and compare, the effect of using Chamomile, Anthocyanoside and their combination, as anti-inflammatory agent to ameliorates, to prevent or control the development of fibrosis due to Bleomycin (BLM). to prepare pulmonary fibrosis model, male Wistar rats weighting 180-220g were assigned to specific groups Rats of each group received intratracheally 1U/100 g of BLM. 20 rats were divided to five comparable groups, as(1) BLM group, (2) saline group, (3) Chamomile group, (4) Anthocyanoside group, (5) combination of Anthocyanoside and Chamomile group. Antioxidative combinations were given as pretreatment and treatment after the rats received Bleomycine. RESULTS: After 3 week, Malondialdehyde (MDA)was measured for each rat's lung. After three weeks, MDA was reduced, compared to BLM group, to 44.27%, 37.80% and 46.07% in Anthocyanoside, Chamomiland combination group, respectively. It was concluded from the present study that administration of combination of Chamomile and Anthocyanoside lead to a significant reduction in Bleomycin-induced MDA. CONCLUSION: The mechanism of the effect of these combinations is possibly the result of phenolic combinations as antioxidant and oxy free radical scavenger and inhibitor of lipid peroxidation. PMID- 26543308 TI - Correlation of Inflammation and Lipoprotein (a) with Hypercoagulability in Hemodialysis Patients. AB - BACKGROUND: Inflammatory and procoagulant markers are potential mediators for the cardiovascular risk in hemodialysis patients. Lipoprotein (a) [Lp(a)], is another important risk factor with inflammatory and procoagulant effects. MATERIALS AND METHODS: In 78 hemodialysis patients and 40 controls, C-reactive protein (CRP), Interleukin-6 (IL-6), lipoprotein (a) [Lp (a)], fibrinogen, D-dimer, von Wilebrand factor (vWF) and serum albumin were determined. RESULTS: CRP, IL-6, Lp(a), fibrinogen, D-dimer and vWF, were significantly higher, and serum albumin was significantly lower in patients compared to controls (24.40 mg/L vs. 6.39 mg/L, p<0.001; 1.92 pg/ml vs. 0.35 pg/ml, 28.05 mg/dL vs.16.25 mg/dL, p<0.001; 3.44 g/L vs. 2.55 g/L, p<0.01; 1.81 ugFEU /ml vs. 0.50 ugFEU /ml, p<0.01; 152.9 % vs. 85.6 %, p<0.001; 32.1 g/L vs. 40.50 g/L, p<0.001). The patients were divided into two groups: 40 patients with CRP levels over than 10 mg/L and 38 with CRP levels in normal range. These parameters showed significant differences between patients with elevated CRP and patients with normal CRP levels. CRP and IL-6 correlated positively with Lp(a), (r = 0.62, p < 0.001; r=0.54, p<0.001), fibrinogen, (r = 0.63, p < 0.001; r = 0.49, p<0.01) D dimer (r = 0.72, p<0.001; r = 0.55, p<0.01), vWF (r = 0.76, p<0.01; r = 0.63, p<0.001) and negatively with serum albumin (r = -0.80, p<0.01; r = -0.60, p<0.001), in patients with elevated CRP, but not in patients with normal CRP levels and controls. CONCLUSION: According to the results hemodialysis patients with increased inflammatory markers, have the elevated Lp(a) and procoagulant markers and the greater risk for atherosclerotic cardiovascular disease. PMID- 26543309 TI - Diagnostic Significance of Reduced IgA in Children. AB - INTRODUCTION: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. At the University Clinical Center Tuzla, children with suspected deficient immune response due to reduced values of IgA, goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. MATERIAL AND METHODS: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. CONCLUSION: The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof. PMID- 26543310 TI - Is Admission Serum Sodium Concentration a Clinical Predictor for the Outcome of Therapy in Critically Ill Poisoned Patients? AB - BACKGROUND: Disorders of serum sodium concentration are some of the most electrolyte abnormalities in the intensive care unit (ICU) patients. These disorders adversely affect the function of vital organs and are associated with increased hospital mortality. PURPOSE: In the present study we aimed to evaluate the effects of serum sodium concentration abnormalities at the time of hospital admission on the clinical outcome of therapy in a cohort of critically ill poisoned patients. METHODS: In this cross-sectional study, 184 critically ill poisoned patients aged >18 years and in the first 8 hours of their poisoning, hospitalized in the ICU of a tertiary care university hospital (Isfahan, Iran) between 2010-2012, were evaluated at the admission time and 24 hours later for serum sodium concentration abnormalities and its relationship with age, gender, consciousness status, ingested drugs and clinical outcome of therapy. The clinical outcome was considered as recovery and mortality. Logistic Regression analysis was performed for predictive variables including serum sodium concentration abnormalities in patients' clinical outcome. FINDINGS: On admission, 152 patients (82.6%) were eunatremic, 21 patients (11.4%) were hyponatremic and 11 patients (6%) were hypernatremic. In the second day eunatremia, hyponatremia and hypernatremia was observed in 84.4%, 13% and 2.2% respectively. Age (OR=1.92; CI=1.18-3.12) and severity of toxicity (OR=1.32; CI=1.12-2.41) were predicting factors of mortality in ICU poisoning patients. CONCLUSIONS: Serum sodium concentration abnormalities are prevalent in critically ill poisoned patient but do not seem to have a predictive value for the clinical outcome of therapy. PMID- 26543311 TI - Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease. AB - INTRODUCTION: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2-), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). OBJECTIVE: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: We observed 160 patients with COPD treated in Clinic for Pulmonary Diseases and TB "Podhrastovi" Sarajevo during three years :from 2012 to 2014. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood PMNL was measured in a stable state of disease at the begging and at the end of investigation. RESULTS: The number of blood PMNL was significantly greater in patients with 3 or more exacerbations per one year (p <0.01). Patients with BHR had significantly greater number blood PMNL than patients without BHR (p< 0.05). Patients with 3 exacerbations per year had a statistically significant increase of number of PMNL between first and last examination (p<0.01). CONCLUSION: There is statistically significant correlation between the number of blood PMNL and the level of BHR in COPD, but future examination need to be done to determine real role and mode of action of PMNL for these processes. PMID- 26543312 TI - Cariogenic Potential of Inhaled Antiasthmatic Drugs. AB - INTRODUCTION: The organism of children with asthma is exposed to the effects of the disease but also the drugs for its treatment. Antiasthmatic drugs have different modes that promote the caries formation which varies according to their basic pharmacological composition. Namely, these drugs have a relatively low pH (5.5), can contain sweeteners such as lactose monohydrate in order to improve the drug taste or both. Frequent consumption of these inhalers in combination with reduced secretion of saliva increases the risk of caries. MATERIAL AND METHODS: The study sample consisted of 200 patients, age from 7-14 years, divided into two groups: control group (n1 = 100) consisted of healthy children and the experimental group consisted of children suffering from asthma (n2 = 100). In both groups of respondents are determined the DMFT index, plaque index value and hygienic-dietary habits using the questionnaire. The subjects in the control group had significantly higher DMFT index than subjects in the experimental group (p = 0.004). It is determined that there are no significant differences in the values of plaque index (p>0.05). CONCLUSION: The effect of different diseases or medications from their treatment, diet and fermentable carbohydrates in the etiology of dental caries cannot be observed outside the living conditions of subjects, their social epidemiologic status, age, habits, oral hygiene, fluoride use, etc. PMID- 26543313 TI - Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus. AB - OBJECTIVES: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. METHODS: This cross-sectional study included 96 patients (age 47-83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG >= 6,1 mmol/L, TG >= 1,7 mmol/L and blood pressure >= 130/85 mm Hg. RESULTS: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= 0,29, p<0,05) in T2DM-MS group of patients. CONCLUSION: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in increasing the risk of liver injury. PMID- 26543314 TI - Treatment of Infertility in Men with Post-traumatic Stress Disorder (PTSD) with the Method of Intrauterine Insemination. AB - OBJECTIVE: Our objective was to determine the effect of PTSD on changing the quality of sperm in veterans with PTSD, and the percentage of successful procedures intrauterine insemination (IUI) as a first-line treatment of male infertility patients with post-traumatic stress disorder (PTSD). PATIENTS AND METHODS: The study is designed as a prospective observational study. The study was started from February 2013 until May of 2014. Our study included a total of 51 patients who were treatment for infertility in private Hospital for gynecology, endocrinology and infertility, IVF Center in Peja, and those who were outpatients treated for chronic PTSD in the Polyclinic, Biolab-Zafi, in Klina the Republic of Kosovo. All subjects divide into two groups; The first, consisting of 21 respondents to the participants of the war in Kosovo, which was established diagnosis of PTSD. The second group of 30 who have not lived in Kosovo for the time War, and without signs of PTSD. RESULTS: Subjects with PTSD were somewhat older than the control group (p = 0.235) but it was not a significant difference (44.5 +/- 5.6 vs 43.8 +/- 2.3). When the question of type of infertility, secondary infertility is significantly higher in patients with PTSD (62% vs 20%) (Table 2). The total number of sperm and semen volume no significant differences between the two groups (p > 0.05). Sperm motility showed a significant reduction in cases of PTSD (p <0.0001), from observation semen parameters were found more abnormal forms of spermatozoa in the ejaculate cases with PTSD (p < 0.0001) (Table 2). The percentage of pregnancies IUI procedure was slightly higher in patients with PTSD than the control group without PTSD (19% vs. 16.6%). CONCLUSION: A combination of analytical oriented psychotherapy techniques and assisted reproductive techniques (ART) such as IUI procedures, increases the chances for healing infertility in patients with PTSD. PMID- 26543315 TI - Treatment of Bone Defects in War Wounds: Retrospective Study. AB - INTRODUCTION: Results of the treatment of open fractures primarily depend on the treatment of connected soft tissue injuries. OBJECTIVE: The aim was to present the experience and methods gained during the treatment of diaphyseal bone defects as a consequence of gunshot fracture soft war trauma. PATIENTS AND METHODS: The study consisted of 116 patients with the diaphyseal bone defect who were treated with the usage of primary and delayed autotransplantation of bones, transplants of the fibula and Ilizarov distraction osteogenesis. RESULTS: The results of compensation of bone defect less than 4 cm and conducted by an early cortico spongioplastics were as follows: good in 8 respondents (45%), satisfactory in 6 (34%) and poor in 4 respondents (21%). In cases of delayed cortico spongioplastics, the above mentioned results were: good in 36 (41%) respondents, satisfactory in 24 (34%) and poor in 16 (25%) respondents. The results of compensation of bone defect greater than 4 cm with the usage of fibular transplant were as follows: good in 3 (38%) respondents, satisfactory in 3 (38%) and poor in 2 (24%), and with the usage of using the Ilizarov method, the results were as follows: good in 8 (57%) respondents, satisfactory in 3 (21.5%) and poor in 3(21.5%) respondents. CONCLUSION: The results showed that, in cases of compensation of bone defects less than 4 cm, the advantage is given to the primary spongioplastics over the delayed one. In cases of compensation of bone defects greater than 4 cm, the advantage is given to the Ilizarov distraction osteogenesis when compared to the fibular transplant. PMID- 26543316 TI - Encrustation of the Ureteral Double J Stent in Patients with a Solitary Functional Kidney - a Case Report. AB - INTRODUCTION: The efficacy of ureteric stents in the management of various urological conditions causing the upper urinary tract obstruction has been extensively proven, and their contribution to urology remains enormous. The clinical use of ureteric stents is associated with several complications. "Stent syndrome," encrustation, migration and urothelial hyperplasia are the most common problems related to long-term ureteral stenting. CASE REPORT: This work presents an interesting case from our practice: a complete encrustation of a classical polyurethane double J stent two and a half months after its initial instillation, in a 70 year old man, with a solitary functioning kidney, as well as successful removal of it by using a simultaneous treatment of extracorporeal lithotripsy and ureteroscopy with a contact disintegration of encrustations and with percutaneous nephrostomy, as an auxiliary procedure for providing of additional urine derivation. CONCLUSION: These problems can be overcome by the introduction of new advanced ureteral stent designs and biomaterials. PMID- 26543317 TI - Patient with FMF and Triple MEFV Gene Mutations. AB - INTRODUCTION: Familial Mediterranean fever (FMF) is the most common auto inflammatory disease with monogenic (MEditerranean FeVer -MEFV- gene) inherited pattern. It mainly affects ethnic groups living along the eastern Mediterranean Sea: Turks, Sephardic Jews, Armenians, and Arabs [1]. Today FMF is not rare disease in other Mediterranean ethnicities, such as Greeks, Italians, and Iranians. CASE REPORT: Here we report a child with complex allele mutations E148Q/V726A/R761H, whilst, whose mother showed E148Q/V726A and his father had R761H/wt in analysis. The severity of the disease and genotype-phenotype correlation of patient showed no significant differences with his mother and other patients with the same two mutations, V726A/R761H, E148Q/V726A, and E148Q/R761H. CONCLUSION: This type of mutation is the first report of triple mutations in FMF patients with no specific phenotype correlation. PMID- 26543318 TI - Disorders of Accommodative Convergation and Accommodation (AC/A) Relations at Traumatic Brain Injury. PMID- 26543319 TI - Repetitive Behavior in Neurodevelopmental Disorders: Clinical and Translational Findings. AB - Repetitive behavior refers to a highly heterogeneous set of responses associated with a wide range of conditions, including normative development. Treatment studies for aberrant repetitive behavior are limited although one promising approach involves conceptualizing such behavior as a generalized inflexibility or lack of variability in responding. Relatively little is known about the neurobiological mechanisms that mediate the development and expression of repetitive behavior, information critical to the design of effective pharmacotherapies, early interventions, and prevention strategies. We will review clinical findings in repetitive behavior as well as findings from animal models highlighting environmental factors and the role of cortical-basal ganglia circuitry in mediating the development and expression of these behaviors. Findings from animal models have included identification of a specific neural pathway important in mediating repetitive behavior. Moreover, pharmacological studies that support the importance of this pathway have led to the identification of novel potential therapeutic targets. Expanding the evidence base for environmental enrichment-derived interventions and focusing on generalized variability in responding will aid in addressing the broader problem of rigidity or inflexibility. PMID- 26543320 TI - FOCUS for Early Childhood: A Virtual Home Visiting Program for Military Families with Young Children. PMID- 26543321 TI - Demonstration that a new flow sensor can operate in the clinical range for cerebrospinal fluid flow. AB - A flow sensor has been fabricated and tested that is capable of measuring the slow flow characteristic of the cerebrospinal fluid in the range from less than 4 mL/h to above 100 mL/h. This sensor is suitable for long-term implantation because it uses a wireless external spectrometer to measure passive subcutaneous components. The sensors are pressure-sensitive capacitors, in the range of 5 pF with an air gap at atmospheric pressure. Each capacitor is in series with an inductor to provide a resonant frequency that varies with flow rate. At constant flow, the system is steady with drift <0.3 mL/h over a month. At variable flow rate, V , the resonant frequency, f0, which is in the 200-400 MHz range, follows a second order polynomial with respect to V . For this sensor system the uncertainty in measuring f0 is 30 kHz which corresponds to a sensitivity in measuring flow of DeltaV = 0.6 mL/hr. Pressures up to 20 cm H2O relative to ambient pressure were also measured. An implantable twin capacitor system is proposed that can measure flow, which is fully compensated for all hydrostatic pressures. For twin capacitors, other sources of systematic variation within clinical range, such as temperature and ambient pressure, are smaller than our sensitivity and we delineate a calibration method that should maintain clinically useful accuracy over long times. PMID- 26543322 TI - Music Engineering as a Novel Strategy for Enhancing Music Enjoyment in the Cochlear Implant Recipient. AB - OBJECTIVE: Enjoyment of music remains an elusive goal following cochlear implantation. We test the hypothesis that reengineering music to reduce its complexity can enhance the listening experience for the cochlear implant (CI) listener. METHODS: Normal hearing (NH) adults (N = 16) and CI listeners (N = 9) evaluated a piece of country music on three enjoyment modalities: pleasantness, musicality, and naturalness. Participants listened to the original version along with 20 modified, less complex, versions created by including subsets of the musical instruments from the original song. NH participants listened to the segments both with and without CI simulation processing. RESULTS: Compared to the original song, modified versions containing only 1-3 instruments were less enjoyable to the NH listeners but more enjoyable to the CI listeners and the NH listeners with CI simulation. Excluding vocals and including rhythmic instruments improved enjoyment for NH listeners with CI simulation but made no difference for CI listeners. CONCLUSIONS: Reengineering a piece of music to reduce its complexity has the potential to enhance music enjoyment for the cochlear implantee. Thus, in addition to improvements in software and hardware, engineering music specifically for the CI listener may be an alternative means to enhance their listening experience. PMID- 26543324 TI - Music in the Brain: From Listening to Playing. PMID- 26543323 TI - Differences according to Sex in Sociosexuality and Infidelity after Traumatic Brain Injury. AB - OBJECTIVE: To explore differences according to sex in sociosexuality and infidelity in individuals with TBI and in healthy controls. PARTICIPANTS: Forty two individuals with mild, moderate, and severe TBI having completed a postacute TBI rehabilitation program, at least six months after injury, and 47 healthy controls. MAIN MEASURES: Sociosexual Orientation Inventory-Revised (SOI-R) and Attitudes toward Infidelity Scale. RESULTS: Overall, men score significantly higher than women in sociosexuality. However, there was a nonsignificant trend towards a reduction of sociosexuality levels in men with TBI. Infidelity levels were comparable in healthy controls and individuals with TBI. In individuals with TBI, less acceptance of infidelity was significantly associated with an unrestricted sociosexual orientation, but not in healthy controls. CONCLUSIONS: As documented in previous cross-cultural studies, men have higher levels of sociosexuality than women. However, men with TBI showed a tendency towards the reduction of sociosexuality. The possibility of a latent explanatory variable is suggested (e.g., post-TBI neuroendocrinological changes). TBI does not seem to have an impact on infidelity, but individuals with TBI who express less acceptance of infidelity also report a more promiscuous mating strategy regarding their behavior, attitudes, and desire. Theoretical implications are discussed in terms of evolutionary theories of human sexuality and neuropsychology. PMID- 26543325 TI - The Hen or the Egg: Inflammatory Aspects of Murine MPN Models. AB - It has been known for some time that solid tumors, especially gastrointestinal tumors, can arise on the basis of chronic inflammation. However, the role of inflammation in the genesis of hematological malignancies has not been extensively studied. Recent evidence clearly shows that changes in the bone marrow niche can suffice to induce myeloid diseases. Nonetheless, while it has been demonstrated that myeloproliferative neoplasms (MPN) are associated with a proinflammatory state, it is not clear whether inflammatory processes contribute to the induction or maintenance of MPN. More provocatively stated: which comes first, the hen or the egg, inflammation or MPN? In other words, can chronic inflammation itself trigger an MPN? In this review, we will describe the evidence supporting a role for inflammation in initiating and promoting MPN development. Furthermore, we will compare and contrast the data obtained in gastrointestinal tumors with observations in MPN patients and models, pointing out the opportunities provided by novel murine MPN models to address fundamental questions regarding the role of inflammatory stimuli in the molecular pathogenesis of MPN. PMID- 26543326 TI - The Effects of Paracoccidioides brasiliensis Infection on GM-CSF- and M-CSF Induced Mouse Bone Marrow-Derived Macrophage from Resistant and Susceptible Mice Strains. AB - Considering the importance of macrophages as the first line of defense against fungal infection and the different roles played by the two M1- and M2-like polarized macrophages, we decided to evaluate the effects of Paracoccidioides brasiliensis infection on GM-CSF- and M-CSF-induced bone marrow-derived macrophages (BMM) from the A/J and B10.A mouse strains, an established model of resistance/susceptibility to PCM, respectively. Upon differentiation, the generated GM- or M-BMMs were characterized by morphological analyses, gene expression profiles, and cytokines production. Our main results demonstrate that GM-BMMs derived from A/J and B.10 produced high levels of pro- and anti inflammatory cytokines that may contribute to generate an unbalanced early immune response. In accordance with the literature, the B10.A susceptible mice lineage has an innate tendency to polarize into M1-like phenotype, whereas the opposite phenotype occurs in A/J resistance mice. In this context, our data support that susceptibility and resistance are strongly correlated with M1 and M2 polarization, respectively. PMID- 26543327 TI - Symmetric Dimethylarginine Is Not Associated with Cumulative Inflammatory Load or Classical Cardiovascular Risk Factors in Rheumatoid Arthritis: A 6-Year Follow-Up Study. AB - Symmetric dimethylarginine (SDMA) indirectly inhibits nitric oxide (NO) synthesis and predicts cardiovascular and all-cause mortality in high-risk patients. The aim of our study was to investigate the associations of cumulative inflammatory burden (assessed by serial measurements of inflammatory markers) and classical cardiovascular (CV) disease risk factors with SDMA in RA patients. 201 RA patients (155 females, median age 67 (59-73)) were assessed at baseline (2006). Classical CV disease risk factors were recorded and systemic inflammation was determined by the measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) SDMA levels were measured by enzyme linked immunosorbent assay. Mean SDMA levels in RA population were 0.40 (0.40 0.53) MUmol/L. No significant association between SDMA and cumulative inflammatory load was established in the analysis. SDMA levels were not found to be significantly related to CV disease risk factors. We explored the potential relationship between SDMA and cumulative inflammatory burden in patients with RA and obtained negative results. SDMA did not relate to CV disease risk factors in our population and its clinical significance as a surrogate marker of endothelial dysfunction in patients with RA remains to be determined. PMID- 26543329 TI - Evaluating the attractiveness of a new light rail extension: Testing simple change and displacement change hypotheses. AB - Many communities in the United States have been adding new light rail to bus predominant public transit systems. However, there is disagreement as to whether opening light rail lines attracts new ridership or merely draws ridership from existing transit users. We study a new light rail line in Salt Lake City, Utah, USA, which is part of a complete street redevelopment. We utilize a pre-test post test control group quasi-experimental design to test two different measures of ridership change. The first measure is calculated from stops along the light rail route; the second assumes that nearby bus stops might be displaced by the rail and calculates ridership change with those stops included as baseline. Both the simple measure (transit use changes on the complete street light rail corridor) and the "displacement" measure (transit use changes in the one-quarter mile catchment areas around new light rail stops) showed significant (p < .01) and substantial (677%) increases in transit passengers compared to pre-light rail bus users. In particular, the displacement analysis discredits a common challenge that when a new light rail line opens, most passengers are simply former bus riders whose routes were canceled in favor of light rail. The study suggests that light rail services can attract additional ridership to public transit systems. In addition, although pre-post control-group designs require time and effort, this project underscores the benefits of such quasi-experimental designs in terms of the strength of the inferences that can be drawn about the impacts of new transit infrastructure and services. PMID- 26543328 TI - Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms. AB - The term myeloproliferative neoplasms (MPN) refers to a heterogeneous group of diseases including not only polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), but also chronic myeloid leukemia (CML), and systemic mastocytosis (SM). Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application. PMID- 26543330 TI - Circulating cancer stem cells: the importance to select. AB - It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients' outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, 'liquid biopsy', which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients' clinical outcome. As compared to non tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing these circulating cancer stem cells, but also highlights current technological limitations. PMID- 26543331 TI - Interaction between circulating cancer cells and platelets: clinical implication. AB - Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells (CTCs), detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis. PMID- 26543332 TI - Circulating tumor cells isolation: the "post-EpCAM era". AB - Circulating tumor cells (CTCs) represent a submicroscopic fraction detached from a primary tumor and in transit to a secondary site. The prognostic significance of CTCs in metastatic cancer patients was demonstrated for the first time more than ten years ago. To date, it seems clear enough that CTCs are highly heterogeneous and dynamically change their shape. Thus, the inadequacy of epithelial cell adhesion molecule (EpCAM) as universal marker for CTCs detection seems unquestionable and alternative methods able to recognize a broader spectrum of phenotypes are definitely needed. In this review the pleiotropic functions of EpCAM are discussed in detail and the role of the molecule in the biology of CTCs is critically dissected. PMID- 26543333 TI - Notes for developing a molecular test for the full characterization of circulating tumor cells. AB - The proved association between the circulating tumor cell (CTC) levels and the patients' survival parameters has been growing interest to investigate the molecular profile of these neoplastic cells among which hide out precursors capable of initiating a new distant metastatic lesion. The full characterization of the tumor cells in peripheral blood of cancer patients is expected to be of help for understanding and (prospectively) for counteracting the metastatic process. The major hitch that is hampering the successful gaining of this result is the lack of a consensus onto standard operating procedures (SOPs) for performing what we generally define as the "liquid biopsy". Here we review the more recent acquisitions in the analysis of CTCs and tumor related nucleic acids, looking to the main open questions that are hampering their definitive employ in the routine clinical practice. PMID- 26543334 TI - Circulating tumor cell isolation: the assets of filtration methods with polycarbonate track-etched filters. AB - Circulating tumor cells (CTCs) arise from primary or secondary tumors and enter the bloodstream by active or passive intravasation. Given the low number of CTCs, enrichment is necessary for detection. Filtration methods are based on selection of CTCs by size using a filter with 6.5 to 8 um pores. After coloration, collected CTCs are evaluated according to morphological criteria. Immunophenotyping and fluorescence in situ hybridization techniques may be used. Selected CTCs can also be cultivated in vitro to provide more material. Analysis of genomic mutations is difficult because it requires adapted techniques due to limited DNA materials. Filtration-selected CTCs have shown prognostic value in many studies but multicentric validating trials are mandatory to strengthen this assessment. Other clinical applications are promising such as follow-up, therapy response prediction and diagnosis. Microfluidic emerging systems could optimize filtration-selected CTCs by increasing selection accuracy. PMID- 26543335 TI - The promise of liquid biopsy in cancer: a clinical perspective. AB - The clinical utility of liquid biopsy in cancer treatment will increase as circulating tumor cells (CTCs) analysis move from the enumeration to the real time measurement of tumor characteristics. Intratumor heterogeneity is becoming increasingly recognized as a major drawback to the shift to personalized medicine. Spatial and temporal heterogeneity might be reflected by the serial assessment of CTCs. Indeed, the developing technologies for CTCs analysis now allow digital genomic and next-generation sequencing approaches, able to differentiate molecular subtypes of the disease and to monitor genetic variation over time. The liquid biopsy of cancer might offer a real-time assessment of tumor biology, providing the opportunity to serially evaluate patients most likely to benefit from targeted drugs based on a dynamic characterization of the disease at the molecular level. Although hurdles remain before liquid biopsy is seen in routine clinical practice, the information derived from CTCs may facilitate the real-time identification of actionable mutations in cancer leading the way toward personalized medicine. PMID- 26543336 TI - Impact of chronic exposure to bevacizumab on EpCAM-based detection of circulating tumor cells. AB - BACKGROUND: Circulating tumor cells (CTCs) are often undetected through the immunomagnetic epithelial cell adhesion molecule (EpCAM)-based CellSearch((r)) System in breast and colorectal cancer (CRC) patients treated with bevacizumab (BEV), where low CTC numbers have been reported even in patients with evidence of progression of disease. To date, the reasons for this discrepancy have not been clarified. This study was carried out to investigate the molecular and phenotypic changes in CRC cells after chronic exposure to BEV in vitro. METHODS: The human CRC cell line WiDr was exposed to a clinically relevant dose of BEV for 3 months in vitro. The expression of epithelial and mesenchymal markers and EpCAM isoforms was determined by western blotting and immunofluorescence. To evaluate the impact of EpCAM variant isoforms expression on CTC enumeration by CellSearch((r)), untreated and treated colon cancer cells were spiked into 7.5 mL of blood from a healthy donor and enumerated by CellSearch((r)). RESULTS: Chronic exposure of CRC cell line to BEV induced decreased expression of EpCAM 40 kDa isoform and increased expression EpCAM 42 kDa isoform, together with a decreased expression of cytokeratins (CK), while no evidence of epithelial to mesenchymal transition (EMT) in treated cells was observed. The recovery rate of cells through CellSearch((r)) was gradually reduced in course of treatment with BEV, being 84%, 70% and 40% at 1, 2 and 3 months, respectively. CONCLUSIONS: We hypothesize that BEV may prevent CellSearch((r)) from capturing CTCs through altering EpCAM isoforms. PMID- 26543337 TI - Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk: a meta-analysis of prospective studies. AB - BACKGROUND: The temporal relationship between hepatitis B virus (HBV) mutations and hepatocellular carcinoma (HCC) remains unclear. METHODS: We conducted a meta analysis including cohort and nested case-control studies to prospectively examine the HCC risk associated with common variants of HBV in the PreS, Enhancer II, basal core promoter (BCP) and precore regions. Pertinent studies were identified by searching PubMed, Web of Science and the Chinese Biological Medicine databases through to November 2014. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected. RESULTS: Twenty prospective studies were identified, which included 8 cohort and 12 nested case-control studies. There was an increased risk of HCC associated with any PreS mutations with a pooled relative risk (RR) of 3.82 [95% confidence interval (CI): 2.59-5.61]. The pooled-RR for PreS deletion was 3.98 (95% CI: 2.28-6.95), which was higher than that of PreS2 start codon mutation (pooled-RR=2.63, 95% CI: 1.30-5.34). C1653T in Enhancer II was significantly associated with HCC risk (pooled-RR=1.83; 95% CI: 1.21-2.76). For mutations in BCP, statistically significant pooled-RRs of HCC were obtained for T1753V (pooled-RR=2.09; 95% CI: 1.49-2.94) and A1762T/G1764A double mutations (pooled-RR=3.11; 95% CI: 2.08-4.64). No statistically significant association with HCC risk was observed for G1896A in the precore region (pooled-RR=0.77; 95% CI: 0.47-1.26). CONCLUSIONS: This study demonstrated that PreS mutations, C1653T, T1753V, and A1762T/G1764A, were associated with an increased risk of HCC. Clinical practices concerning the HCC risk prediction and diagnosis may wish to focus on patients with these mutations. PMID- 26543338 TI - Prognostic value of clinicopathological characteristics in patients with pancreatic cancer. AB - BACKGROUND: The purpose of this study was to analyze the effects of all clinical characteristics on the overall survival time, in order to provide a basis for determining the prognostic factor of patients with pancreatic cancer. METHODS: A total of 103 pancreatic cancer patients were admitted to the Department of Radiotherapy and Chemotherapy of the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between January 2002 and December 2012. There were 68 men and 35 women; the median age was 62 years. Diagnoses of pancreatic cancer in all patients were confirmed by histopathology, cytology, or clinical diagnosis. The Kaplan-Meier method was performed to calculate the overall survival rate. The log-rank method was used to examine the univariate analysis. The Cox regression model was performed for multivariate analysis. RESULTS: The median survival time was 293 days, the 1-, 2-, and 3-year survival rates were 27.18%, 5.83%, and 1.94%, respectively. Cox regression analysis revealed that age (P=0.015), Karnofsky performance status (PS) (P=0.002), surgical types (P<0.001), and platelet counts (P<0.001) were independent prognostic factors affecting the overall survival of patients with pancreatic cancer. CONCLUSIONS: Pancreatic cancer had a poor prognosis, the general physical condition, age, the availability of radical surgery, and platelet counts were factors influencing the overall survival of patients with pancreatic cancer. PMID- 26543339 TI - Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma. AB - BACKGROUND: The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients. METHODS: Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. RESULTS: Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS. CONCLUSIONS: CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients. PMID- 26543340 TI - A PTEN translational isoform has PTEN-like activity. AB - BACKGROUND: To identify PTEN isoform and explore its potential role in tumor suppression. METHODS: Western blotting, over-expression, shRNA mediated knocking down, and bioinformatic analysis were used to identify PTEN isoform and test its effect on PI3K-Akt signaling pathway. Cell proliferation, apoptosis, and migration assays were used to test PTEN isoform's biological activities. RESULTS: The PTEN isoform is about 15 kDa bigger than PTEN and its expression is dependent on PTEN status. Immunoprecipitation for PTEN isoform followed by screening with antibodies against ISG15, SUMO1/2/3, Ubiquitin, and Nedd8 showed the identified PTEN isoform is not a general proteinaceous post-translational modification. In addition, overexpression of PTEN cDNA in cells did not generate PTEN isoform whereas knocking-down of PTEN reduced the protein levels of both PTEN and PTEN isoform in a proportional manner. Analysis of PTEN DNA sequence disclosed an alternative translational starting code (CTG) upstream of canonical PTEN coding sequence. Expression of cloned PTEN isoform generated a protein with a size about 15 kDa bigger than PTEN and suppressed PI3K-Akt signaling pathway in cells. Overexpression of PTEN isoform also led to decrease in cell growth and enhanced serum starvation-and UV irradiation-induced apoptosis through activation of Caspase 3. Finally, expression of PTEN isoform inhibited cell migration in scratch assay. CONCLUSIONS: PTEN isoform has PTEN-like activity and might be a new tumor suppressor. PMID- 26543341 TI - New book Gastric Cancer first launched on the 10(th) CGCC. PMID- 26543342 TI - The final contest of 2015 Chinese Young Surgeon Contest-surgery for gastric cancer. PMID- 26543343 TI - Demographic and Parenting Correlates of Adolescent Sleep Functioning. AB - Despite the importance of parenting practices for adolescent adjustment, parenting correlates of adolescent sleep functioning remain understudied. This study delineated patterns of sleep functioning in a sample of ethnically diverse, low-income, adolescents and examined associations among three types of parenting practices (parental involvement, parent-child conflict, and parental control) and adolescent sleep functioning (difficulties initiating sleep and maintaining sleep, and sleep duration). Adolescents (N = 91, 11-19 years old) self-reported on sleep functioning and parenting practices. Results showed that in the preceding month, 60.5% of adolescents had difficulties initiating sleep and 73.6% had difficulties maintaining sleep. Most adolescents slept 8 or more hours per night, but 30.7% slept less than 8 hours. Latino adolescents slept longer and had fewer difficulties maintaining sleep than non-Latino. High school students had fewer difficulties maintaining sleep than their middle school counterparts; conversely, older adolescents experienced shorter sleep duration than younger ones. Adolescents whose parents had post-secondary education had shorter sleep duration than those whose parents had not graduated from high school. Parental control was correlated with fewer difficulties initiating sleep, whereas parent child conflict was correlated with more difficulties maintaining sleep. There were no parenting correlates of sleep duration. Latino adolescents had better sleep profiles than non-Latino ones. Regression analyses showed that parental control and parent-child conflict were associated with adolescent sleep functioning across ethnicities. Results suggest that parenting practices, as well as demographic characteristics, are associated with adolescent sleep functioning and should be taken into account in interventions aimed at improving sleep functioning among adolescents. PMID- 26543344 TI - The Use of Endobronchial Ultrasound in the Diagnosis of Subacute Pulmonary Histoplasmosis. AB - Objective. Endobronchial ultrasound (EBUS) utility in diagnosis in malignant and granulomatous mediastinal disease has been well demonstrated. We propose to examine the role of EBUS transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of subacute pulmonary histoplasmosis (SPH) with mediastinal lymphadenopathy in an area where histoplasmosis is endemic. Methods. A retrospective review was performed in a single academic institution between 2009 and 2012 of patients referred for EBUS-TBNA who had radiographic imaging and clinical symptomatology suspicious for SPH. Seven patients were reviewed. TBNA results showing granulomatous disease with areas of necrosis in the appropriate clinical setting were considered to be adequate for the diagnosis of SPH when alternative diagnosis was excluded. Patients underwent further clinical follow-up of 12 months to determine the final diagnosis. Results. All seven patients were felt to have SPH diagnosis reached by a combination of clinical presentation, EBUS-TBNA results, fungal serologies, and antigen testing. None of the patients needed further invasive procedures. Conclusions. EBUS-TBNA is a minimally invasive tool that can be used to support a diagnosis of SPH in patients with a high degree of clinical suspicion. EBUS-TBNA should be considered as an adjunctive diagnostic procedure for patients with SPH in an appropriate clinical setting. PMID- 26543345 TI - Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease. AB - Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue. PMID- 26543346 TI - Screening of Transcription Factors Involved in Fetal Hemoglobin Regulation Using Phylogenetic Footprinting. AB - Fetal hemoglobin (Hb F) is an important genetic modulator of the beta hemoglobinopathies. The regulation of Hb F levels is influenced by transcription factors. We used phylogenetic footprinting to screen transcription factors that have binding sites in HBG1 and HBG2 genes' noncoding regions in order to know the genetic determinants of the Hb F expression. Our analysis showed 354 conserved motifs in the noncoding regions of HBG1 gene and 231 motifs in the HBG2 gene between the analyzed species. Of these motifs, 13 showed relation to Hb F regulation: cell division cycle-5 (CDC5), myelo-blastosis viral oncogene homolog (c-MYB), transcription factor CP2 (TFCP2), GATA binding protein 1 (GATA-1), GATA binding protein 2 (GATA-2), nuclear factor erythroid 2 (NF-E2), nuclear transcription factor Y (NF-Y), runt-related transcription factor 1 (RUNX-1), T cell acute lymphocytic leukemia 1 (TAL-1), YY1 transcription factor (YY1), beta protein 1 (BP1), chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), and paired box 1 (PAX-1). The last three motifs were conserved only in the noncoding regions of the HBG1 gene. The understanding of genetic elements involved in the maintenance of high Hb F levels may provide new efficient therapeutic strategies in the beta-hemoglobinopathies treatment, promoting reduction in clinical complications of these genetic disorders. PMID- 26543347 TI - Clinical performance of KeraSoft((r)) IC in irregular corneas. AB - PURPOSE: This study evaluated the clinical performance of KeraSoft((r)) IC (KIC) soft contact lenses in subjects with irregular corneas. PATIENTS AND METHODS: This was a 12-month, prospective, open-label, observational study, which enrolled 43 subjects who were 18 years of age or older with irregular corneas. Subjects were fit according to the KIC Fitting Manual (kerasoftic.com). After achieving best fit according to the fitting manual, lenses were assessed for comfort, vision, centration, rotation, and movement. Subjects were instructed to wear their lenses between 8 and 16 hours each day. Assessments at the exit visit included logMAR visual acuity with high and low contrast, spherocylindrical overrefraction, slit-lamp findings, adverse events, and subjective outcomes. RESULTS: The average base curve was 8.17+/-0.32 mm (n=70 eyes), and the average diameter dispensed was 14.53+/-0.12 mm (n=70 eyes). From the baseline to 12 months, there was statistically significant improvement in logMAR visual acuity with high contrast (P=0.038), but no significant difference in low-contrast visual acuity was observed (P>0.05). Slit-lamp findings were <= grade 1 for the majority of subjects (89%). Two nonserious adverse events were reported for two of the 84 enrolled eyes (two subjects). At 12 months, subjects reported improvements from habitual baseline for comfort and vision, both upon insertion and just before removal of lenses. CONCLUSION: Clinical outcomes at 12 months showed good visual, safety, and subjective outcomes for subjects with corneal irregularities who wore KeraSoft((r)) IC soft contact lenses. PMID- 26543348 TI - Autologous platelet concentrate in surgery for macular detachment associated with congenital optic disc pit. AB - PURPOSE: To evaluate the anatomical and functional results obtained with pars plana vitrectomy (PPV) plus autologous platelet concentrate (APC) as a treatment for macular detachment associated with optic disc pit (ODP). METHODS: We performed a prospective interventional study of 19 eyes of 19 consecutive patients with posterior macular detachment due to ODP. All patients underwent PPV, posterior hyaloid peeling, fluid-air exchange, injection of 0.05 mL of APC over the ODP and 15% perfluoropropane (C3F8) endotamponade. Postoperative measures included face-up positioning for 2 hours and then avoidance of the face up position during the ensuing 10 days. All patients underwent complete ophthalmologic examination and optical coherence tomography preoperatively at 1 month, 3 months, 6 months, 9 months, and 12 months postoperatively and then annually. Outcome measures were best corrected visual acuity (BCVA) by logMAR, improvement of quality of vision, macular attachment, and resolution of intraretinal schisis-like separation. RESULTS: Preoperatively, the median BCVA was 0.70 (range: 0.30-1.70) and all patients showed improved visual acuity after surgery; BCVA was 0.22 (range: 0.07-0.52) at 12 months follow-up. All patients showed complete reabsorption of intraretinal fluid (median time: 3.5 months [range: 2-8 months]) and macular attachment at the end of follow-up (median: 60 months [range: 12-144 months]), with stable or improved visual acuity. No reoperations were needed and no major adverse events were recorded. CONCLUSION: For macular detachment associated with ODP, the combination of PPV, posterior hyaloid peeling, APC, and C3F8 tamponade is a highly effective alternative technique with stable anatomical and functional results. PMID- 26543349 TI - Evaluation of surface water characteristics of novel daily disposable contact lens materials, using refractive index shifts after wear. AB - PURPOSE: Contact lens wearers today spend much time using digital display devices. Contact lens manufacturers are challenged to develop products that account for longer periods of time where blink rate is reduced and tear-film evaporation rate is increased, affecting both visual acuity and comfort. Two manufacturers recently introduced novel daily disposable contact lenses with high surface water content. The objective of the present study was to compare surface water characteristics before and after initial wear of recently introduced nesofilcon A and delefilcon A high surface water lenses with those of etafilcon A lenses. PATIENTS AND METHODS: Twenty healthy subjects wore each of the three lens types studied in a randomly determined order for 15 minutes. After each wearing, lenses were removed and the surface refractive index (RI) of each lens was immediately measured. RESULTS: The mean RI of the unworn delefilcon A lens was 1.34, consistent with water content in excess of 80%. After 15 minutes of wear, the surface RI shifted to 1.43, consistent with its reported 33% bulk water content. In contrast, the mean surface RI of the nesofilcon A lens was 1.38, both initially and after 15 minutes of wear, and that of the etafilcon A lens was 1.41 initially and 1.42 after 15 minutes of wear. CONCLUSION: The surface of the delefilcon A lens behaves like a high water hydrogel upon insertion but quickly dehydrates to behave like its low-water silicone-hydrogel bulk material with respect to surface water content during wear, while both nesofilcon A and etafilcon A lenses maintain their water content during initial wear. The nesofilcon A lens appears unique among high water lenses in maintaining high surface and bulk water content during wear. This is important because changes in surface RI due to dehydration are reported to lead to visual aberration affecting user experience. PMID- 26543350 TI - Short-term effects of relaxation music on patients suffering from primary open angle glaucoma. AB - PURPOSE: To evaluate whether additive relaxation music (RM) has an adjuvant short term effect on physiological and psychological parameters in patients with primary open-angle glaucoma. METHODS: Prospective, randomized clinical trial. Patients in the therapy group (TG) received a 30-minute RM via headphones, whereas members of the control group (CG) did not. Best corrected visual acuity, intraocular pressure, visual field testing, short- and long-term mental states, and blood levels of different stress hormones were analyzed and compared. RESULTS: A total of 25 (61%)/16 (39%) patients were assigned to the TG/CG. Best corrected visual acuity, daily intraocular pressure, and short-term mental state (KAB) development were significantly better in the TG in comparison to controls. Visual field testing, long-term mental well-being (profile of mood states), and adrenalin, cortisol, and endothelin-I blood levels did not differ significantly between both groups. CONCLUSION: Additive RM applied on a daily basis can positively impact various physiological and psychological parameters in the short term. PMID- 26543351 TI - Overexpression of PI3K p110alpha contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts. AB - Gastric cancer is one of the most virulent malignant diseases and is the second leading cause of cancer mortality in the world. The receptor tyrosine kinase MET is constitutively activated in many gastric cancers and its expression is strictly required for survival of some gastric cancer cells. Targeting gastric cancers with amplified or abnormally activated MET may have therapeutic benefit based on nonclinical and emerging clinical findings. However, one of the major problems of therapies targeting tyrosine kinases is that many tumors are not responsive to treatment or eventually develop resistance to the drugs. This study aims to understand the mechanisms of MET resistance in gastric SNU-5 xenografts which developed resistance to PHA665752, a MET inhibitor, through long-period tyrosine kinase inhibitor exposure. In the current study, we found that PI3K p110alpha is overexpressed in PHA665752-resistant SNU-5 xenografts. These findings showed that high PI3K p110alpha expression contributes to tyrosine kinase inhibitor resistance. In addition, we reported the development of a carcinogen-induced gastric cancer model that recapitulates PI3K p110alpha expression in human disease, which will serve as a useful model to study PI3K p110alpha's biology and its effectiveness as a novel biomarker and a molecular target for gastric cancer. Ultimately, PI3K p110alpha represents a novel target for gastric cancer. PMID- 26543352 TI - Evaluation of the cardiovascular effects of varenicline in rats. AB - BACKGROUND: Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events. OBJECTIVE: To determine the cardiovascular toxicity induced by varenicline in rats. MATERIALS AND METHODS: We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 MUg/kg/day varenicline on days 1-3, 9 MUg/kg twice daily on days 4-7, and 18 MUg/kg twice daily on days 8-90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed. RESULTS: Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups. CONCLUSION: Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation. PMID- 26543353 TI - Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures. AB - Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical practice. Finally, pharmacological properties of BRV are summarized with a description of its pharmacokinetics, safety, and potential/known drug-drug interactions. PMID- 26543354 TI - Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency. AB - Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID- 26543355 TI - Antibacterial activity and therapeutic efficacy of Fl-P(R)P(R)P(L)-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection. AB - The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-P(R)P(R)P(L)-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-P(R)P(R)P(L)-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-P(R)P(R)P(L)-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-P(R)P(R)P(L)-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-P(R)P(R)P(L)-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1beta) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-P(R)P(R)P(L)-5 in the treatment of staphylococcal skin infections. PMID- 26543356 TI - A comparison between uni- and multidimensional frailty measures: prevalence, functional status, and relationships with disability. AB - BACKGROUND: Over the years, a plethora of frailty assessment tools has been developed. These instruments can be basically grouped into two types of conceptualizations - unidimensional, based on the physical-biological dimension - and multidimensional, based on the connections among the physical, psychological, and social domains. At present, studies on the comparison between uni- and multidimensional frailty measures are limited. OBJECTIVE: The aims of this paper were: 1) to compare the prevalence of frailty obtained using a uni- and a multidimensional measure; 2) to analyze differences in the functional status among individuals captured as frail or robust by the two measures; and 3) to investigate relations between the two frailty measures and disability. METHODS: Two hundred and sixty-seven community-dwelling older adults (73.4+/-6 years old, 59.9% of women) participated in this cross-sectional study. The Cardiovascular Health Study (CHS) index and the Tilburg Frailty Indicator (TFI) were used to measure frailty in a uni- and multidimensional way, respectively. The International Physical Activity Questionnaire, the Center of Epidemiologic Studies Depression scale, and the Loneliness Scale were administered to evaluate the functional status. Disability was assessed using the Groningen Activity Restriction Scale. Data were treated with descriptive statistics, one-way analysis of variance, correlations, and receiver operating characteristic analyses through the evaluation of the areas under the curve. RESULTS: Results showed that frailty prevalence rate is strictly dependent on the index used (CHS =12.7%; TFI =44.6%). Furthermore, frail individuals presented differences in terms of functional status in all the domains. Frailty measures were significantly correlated with each other (r=0.483), and with disability (CHS: r=0.423; TFI: r=0.475). Finally, the area under the curve of the TFI (0.833) for disability was higher with respect to the one of CHS (0.770). CONCLUSION: Data reported here confirm that different instruments capture different frail individuals. Clinicians and researchers have to consider the different abilities of the two measures to detect frail individuals. PMID- 26543357 TI - Additive effect of linseed oil supplementation on the lipid profiles of older adults. AB - BACKGROUND: Linseed oil has been investigated as a rich source of n-3 series polyunsaturated fatty acids, which mainly produce a non-atherogenic lipid profile. The objective of this study was to investigate the effect of linseed oil supplementation associated with nutritional guidelines on the lipid profiles of older adults, according to the intake of saturated fatty acids (SFA). METHODS: We conducted a double-blind, placebo-controlled clinical trial with 110 older adults randomized in two groups: placebo and linseed oil. The linseed oil group received supplementation with 3 g of linseed oil. Both groups received nutritional guidance and were supplemented for 90 days with monthly blood collection for biochemical analysis. The dietary intake of saturated fat was subdivided into low (<7% SFA/day of the total energy value) and high consumption groups (>7% SFA/day of the total energy value). RESULTS: Low SFA (<7% SFA/day of total energy value) consumption was associated with lower total cholesterol concentrations. However, we observed that the linseed oil group, including older adults who consumed >7% SFA/day, had a greater reduction in total cholesterol than the placebo group (P=0.020). The same was observed for low-density lipoprotein (LDL) cholesterol (P<0.050), suggesting an additive effect of linseed oil and diet. High-density lipoprotein (HDL) cholesterol concentrations were increased significantly in only the linseed group, suggesting that the nutritional intervention alone did not improve HDL cholesterol. CONCLUSION: The results suggest that the nutritional intervention was effective, but linseed oil showed notable effects by increasing the HDL cholesterol concentration. In addition, consumption of <7% SFA/day of the total energy value increased the effect of linseed oil, demonstrating the importance of reducing the consumption of saturated fat. PMID- 26543358 TI - Outcomes of a multimodal cognitive and physical rehabilitation program for persons with mild dementia and their caregivers: a goal-oriented approach. AB - BACKGROUND: Nonpharmacological interventions such as exercise and cognitive rehabilitation programs have shown promise in reducing the impact of dementia on the individual and the caregiver. In this study, we examine the effect of a multimodal cognitive and physical rehabilitation program for persons with mild dementia and their caregivers using conventional measures of cognition, behavior, quality of life (QoL), and caregiver burden together with goal attainment scaling (GAS), an individualized outcome measure. METHODS: Goals were set at baseline, and GAS score was calculated at the end of the program. Participants were also assessed with the Chinese Mini-Mental State Examination, functional and behavioral scales (Barthel Index), Instrumental Activities of Daily Living, Neuropsychiatric Inventory Questionnaire, QoL, and caregiver burden using EuroQol five dimension questionnaire and Zarit Burden Interview (ZBI). Differences in median scores postintervention were obtained. Further analysis of caregiver burden was undertaken utilizing the multidimensional classification of burden on the ZBI. RESULTS: Thirty-four (61.8%) patients were assessed to have met their goals (GAS score>=50). Mean (standard deviation) GAS score was 48.6 (6.5). Cognition goals were set in only 20.6%, followed by goals to improve engagement and socialization; reduce caregiver stress; and improve physical function, behavior, and mood. Median scores in the cognitive, functional, and QoL measures did not differ significantly pre- and postintervention. The intervention had a positive impact on role strain, a unique dimension of caregiver burden. CONCLUSION: This study provides evidence that a multimodal approach combining physical exercise and cognitive rehabilitation improves goal attainment and caregiver burden in individuals and caregivers of persons with mild dementia. PMID- 26543359 TI - Zabofloxacin versus moxifloxacin in patients with COPD exacerbation: a multicenter, double-blind, double-dummy, randomized, controlled, Phase III, non inferiority trial. AB - A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals. Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, -7.7%-8.6%). Intention-to treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, 0.2%; 95% confidence interval, -9.0%-8.8%), respectively. These results confirm that zabofloxacin is not inferior to moxifloxacin. The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22). Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group. Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97). The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12). Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. PMID- 26543360 TI - The stats are in: an update on statin use in COPD. AB - COPD is a chronic inflammatory disease of the lungs associated with an abnormal inflammatory response to noxious particles, the most prevalent of which is cigarette smoke. Studies have demonstrated that cigarette smoking is associated with activation of the bone marrow, and chronic smoking can lead to the inflammatory changes seen in COPD. Due to the inflammatory nature of the disease, medications affecting the inflammatory pathway may have clinical benefit and are being evaluated. One such class of medications, HMG-CoA reductase inhibitors, have been evaluated in the COPD population. Early studies have suggested that HMG CoA reductase inhibitors have a variety of benefits in COPD including improvements in inflammatory markers, exacerbation rates, and mortality rates. However, the majority of this data comes from retrospective cohort studies, suggesting the need for randomized controlled trials. Recently, two randomized controlled trials, STATCOPE and RODEO, evaluated the benefit of HMG-CoA reductase inhibitors in the COPD population and found no benefit in exacerbation rates and vascular or pulmonary function, respectively. These results are reflected in practice guidelines, which do not support the use of HMG-CoA reductase inhibitors for the purpose of reducing COPD exacerbations. PMID- 26543361 TI - Time trends in coronary revascularization procedures among people with COPD: analysis of the Spanish national hospital discharge data (2001-2011). AB - BACKGROUND: People with COPD suffering from coronary artery disease are frequently treated with revascularization procedures. We aim to compare trends in the use and outcomes of these procedures in COPD and non-COPD patients in Spain between 2001 and 2011. METHODS: We identified all patients who had undergone percutaneous coronary interventions (PCIs) and coronary artery bypass graft (CABG) surgeries, using national hospital discharge data. Discharges were grouped into: COPD and no COPD. RESULTS: From 2001 to 2011, 428,516 PCIs and 79,619 CABGs were performed. The sex and age-adjusted use of PCI increased by 21.27% per year from 2001 to 2004 and by 5.47% per year from 2004 to 2011 in patients with COPD. In-hospital mortality (IHM) among patients with COPD who underwent a PCI increased significantly from 2001 to 2011 (odds ratio 1.11; 95% confidence interval 1.03-1.20). Among patients with COPD who underwent a CABG, the sex and age-adjusted CABG incidence rate increased by 9.77% per year from 2001 to 2003, and then decreased by 3.15% through 2011. The probability of dying during hospitalization in patients who underwent a CABG did not change significantly in patients with and without COPD (odds ratio, 1.06; 95% confidence interval 0.96 1.17). CONCLUSION: The annual percent change in PCI procedures increased in COPD and non-COPD patients. We found a decrease in the use of CABG procedures in both groups. IHM was higher in patients with COPD who underwent a PCI than in those without COPD. However, COPD did not increase the probability of dying during hospitalization in patients who underwent a CABG. PMID- 26543362 TI - Forecasting COPD hospitalization in the clinic: optimizing the chronic respiratory questionnaire. AB - PURPOSE: Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care. There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care. The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use. Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD. Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization. PATIENTS AND METHODS: A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes. The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8+/-16.7, and modified Medical Research Council dyspnea scale score of 2+/-1.13. RESULTS: Our analysis validated the original CRQ-SAS domains. Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization. We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD. CONCLUSION: We identified three themes - fear of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms - as important patient-reported outcomes to predict hospitalizations, and propose a short and easy algorithm to forecast hospitalizations in patients with COPD. PMID- 26543363 TI - Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model. AB - The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1+/-3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy. PMID- 26543365 TI - Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes. AB - A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real time observation of cellular uptake, and in vivo tissue distribution study, co encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. PMID- 26543364 TI - Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model. AB - BACKGROUND: Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. OBJECTIVE: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. METHODS: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-alpha levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. RESULTS: Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175+/-17 nm and span of 1.6+/-0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-alpha (P=0.001) and IL-1alpha (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX. CONCLUSION: The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA. PMID- 26543366 TI - Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo. AB - The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM) by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution enhanced dispersion by supercritical fluids [SEDS]). The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS) was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w), flow rate of solution (mL/min), and pressure (MPa) as independent variables. Particle size, entrapment efficiency (EE), and drug loading (DL) were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, -62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC(0 t) of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes. PMID- 26543367 TI - Frequency of anemia in chronic psychiatry patients. AB - PURPOSE: Anemia could cause psychiatric symptoms such as cognitive function disorders and depression or could deteriorate an existing psychiatric condition when it is untreated. The objective of this study is to scrutinize the frequency of anemia in chronic psychiatric patients and the clinical and sociodemographic factors that could affect this frequency. METHODS: All inpatients in our clinic who satisfied the study criteria and received treatment between April 2014 and April 2015 were included in this cross-sectional study. Sociodemographic data for 378 patients included in the study and hemoglobin (Hb) and hematocrit values observed during their admission to the hospital were recorded in the forms. Male patients with an Hb level of <13 g/dL and nonpregnant female patients with an Hb level of <12 g/dL were considered as anemic. FINDINGS: Axis 1 diagnoses demonstrated that 172 patients had depressive disorder, 51 patients had bipolar disorder, 54 patients had psychotic disorder, 33 patients had conversion disorder, 19 patients had obsessive-compulsive disorder, 25 patients had generalized anxiety disorder, and 24 patients had other psychiatric conditions. It was also determined that 25.4% of the patients suffered from anemia. Thirty five percent of females and 10% of males were considered as anemic. The frequency of anemia was the highest among psychotic disorder patients (35%), followed by generalized anxiety disorder patients (32%), and obsessive-compulsive disorder patients (26%). Anemia was diagnosed in 22% of depressive disorder patients, 25% of bipolar disorder patients, and 24% of conversion disorder patients. RESULTS: The prevalence of anemia among chronic psychiatry patients is more frequent than the general population. Thus, the study concluded that it would be beneficial to consider the physical symptoms and to conduct the required examinations to determine anemia among this patient group. PMID- 26543368 TI - Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression. AB - BACKGROUND: Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The GranadSigmap study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andalusia (South Spain), being one of its main objectives to identify genetic and environmental risk factors for MDD and other major psychiatric disorders. In this study, we focused on the possible association of 91 candidate single nucleotide polymorphisms (SNPs) with MDD. METHODS: A total of 711 community-based individuals participated in the GranadSigmap study. All individuals were extensively assessed for clinical, psychological, sociodemographic, life style, and other environmental variables. A biological sample was also collected for subsequent genetic analyses in 91 candidate SNPs for MDD. DSM-IV diagnosis of MDD was used as the outcome variable. Logistic regression analysis assuming an additive genetic model was performed to test the association between MDD and the genetic data. The experiment-wide significance threshold adjusted with the SNP spectral decomposition method provided a maximum P-value (8*10(-3)) required to identify an association. Haplotype analyses were also performed. RESULTS: One SNP (rs623580) located in the tryptophan hydroxylase 1 gene (TPH1; chromosome 11), one intergenic variant (rs9526236) upstream of the 5-hydroxytryptamine receptor 2A gene (HTR2A; chromosome 13), and five polymorphisms (rs17689966, rs173365, rs7209436, rs110402, and rs242924) located in the corticotropin-releasing hormone receptor 1 gene (CRHR1; chromosome 17), all showed suggestive trends for association with MDD (P<0.05). Within CRHR1 gene, the TATGA haplotype combination was found to increase significantly the risk for MDD with an odds ratio =1.68 (95% CI: 1.16-2.42, P=0.006). CONCLUSION: Although limited, perhaps due to insufficient sample size power, our results seem to support the notion that the hypothalamic-pituitary-adrenal and serotonergic systems are likely to be involved in the genetic susceptibility for MDD. Future studies, including larger samples, should be addressed for further validation and replication of the present findings. PMID- 26543369 TI - Electroencephalography signatures of attention-deficit/hyperactivity disorder: clinical utility. AB - The techniques and the most important results on the use of electroencephalography (EEG) to extract different measures are reviewed in this work, which can be clinically useful to study subjects with attention deficit/hyperactivity disorder (ADHD). First, we discuss briefly and in simple terms the EEG analysis and processing techniques most used in the context of ADHD. We review techniques that both analyze individual EEG channels (univariate measures) and study the statistical interdependence between different EEG channels (multivariate measures), the so-called functional brain connectivity. Among the former ones, we review the classical indices of absolute and relative spectral power and estimations of the complexity of the channels, such as the approximate entropy and the Lempel-Ziv complexity. Among the latter ones, we focus on the magnitude square coherence and on different measures based on the concept of generalized synchronization and its estimation in the state space. Second, from a historical point of view, we present the most important results achieved with these techniques and their clinical utility (sensitivity, specificity, and accuracy) to diagnose ADHD. Finally, we propose future research lines based on these results. PMID- 26543370 TI - Decompressive craniectomy for severe traumatic brain injury patients with fixed dilated pupils. AB - OBJECTIVE: The outcome of decompressive craniectomy (DC) for severe traumatic brain injury (sTBI) patients with fixed dilated pupils (FDPs) is not clear. The objective of this study was to validate the outcome of DC in sTBI patients with FDPs. PATIENTS: We retrospectively collected data from 207 sTBI patients with FDPs during the time period of May 4, 2003-October 22, 2013: DC group (n=166) and conservative care (CC) group (n=41). MEASUREMENTS: Outcomes that were used as indicators in this study were mortality and favorable outcome. The analysis was based on the Glasgow Outcome Scale recorded at 6 months after trauma. RESULTS: A total of 49.28% patients died (39.76% [DC group] vs 87.80% [CC group]). The mean increased intracranial pressure values after admission before operation were 36.20+/-7.55 mmHg in the DC group and 35.59+/-8.18 mmHg in the CC group. After performing DC, the mean ICP value was 14.38+/-2.60 mmHg. Approximately, 34.34% sTBI patients with FDPs in the DC group gained favorable scores and none of the patients in the CC group gained favorable scores. CONCLUSION: We found that DC plays a therapeutic role in sTBI patients with FDPs, and it is particularly important to reduce intracranial pressure as soon as possible after trauma. For the patients undergoing DC, favorable outcome and low mortality could be achieved. PMID- 26543371 TI - Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations. AB - Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the "as-needed" use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. PMID- 26543372 TI - Assessing Nociception by fMRI of the Human Spinal Cord: A Systematic Review. AB - OBJECTIVE: To assess the use of fMRI of the spinal cord in measuring noxious stimulation. METHODS: The Scopus, Medline, EMBASE, and Web of Science databases were searched, along with the reference lists of included articles. Two independent reviewers screened abstracts, full-text articles, and extracted data. Original research was included if fMRI of the human spinal cord was used to measure responses to noxious stimulation. RESULTS: Of the 192 abstracts screened, 19 met the search criteria and were divided according to their focus: investigating pain responses (n = 6), methodology (n = 6), spinal cord injury (n = 2), or cognition-pain interactions (n = 5). All but one study appear to have observed activity in ipsilateral and dorsal gray matter regions in response to noxious stimuli, although contralateral or ventral activity was also widely observed. CONCLUSIONS: Although nociception can be investigated using spinal fMRI, establishing reliability, standardizing methodology, and reporting of results will greatly advance this field. PMID- 26543373 TI - MicroRNA-766 targeting regulation of SOX6 expression promoted cell proliferation of human colorectal cancer. AB - MicroRNAs (miRNAs) have emerged as important regulators of cancer-cell biological processes. Previous studies have shown that miR-766 plays an important role in a variety of biological processes in various human cancers. However, the underlying mechanism of miR-766 in colorectal cancer (CRC) cells remains unclear. In this study, we investigated miR-766's role in CRC cell proliferation. Polymerase chain reaction results showed that miR-766 expression was significantly upregulated in CRC tissues and cells. Ectopic expression of miR-766 promoted cell growth and anchorage-independent growth in CRC cells. Bioinformatic analysis predicted SOX6, a potential target of miR-766, acting as a tumor suppressor. Luciferase reporter assay results demonstrated that miR-766 directly bound to the 3'-untranslated region of SOX6. Overexpression of miR-766 suppressed SOX6 expression, resulting in the downregulation of p21 and upregulation of cyclin D1. In a further experiment, SOX6-silenced SW480 cells transfected with miR-766 promoted cell growth, suggesting that downregulation of SOX6 was required for miR-766-induced CRC cell proliferation. Taken together, these results suggested that miR-766 represents an onco-miRNA and participates in the development of CRC by modulating SOX6 expression. PMID- 26543374 TI - rs712 polymorphism within let-7 microRNA-binding site might be involved in the initiation and progression of colorectal cancer in Chinese population. AB - rs712 within 3'-untranslated region of KRAS can affect the specific binding between the mRNA and its targeted microRNAs, leading to the activation of KRAS oncogene. However, the possible association between the locus and susceptibility to colorectal cancer (CRC) remains unclear. We investigated genotypes of the locus in 586 cases and 476 controls to explore the possible association between them. Results of our case-control study showed that genotypes TT (6.5% vs 2.5%, P=0.002, adjusted odds ratio [OR] =2.810, 95% confidence interval [CI] =1.342 5.488) and GT/TT (36.5% vs 30.5%, P=0.038, adjusted OR =1.342, 95% CI =1.030 1.712) and allele T (21.5% vs 6.5%, P=0.004, adjusted OR =1.328, 95% CI =1.105 1.722) of rs712 were significantly associated with an increased risk of CRC, and the significant association was also observed in the recessive model (TT vs GG/GT, 6.5% vs 2.5%, P=0.003, adjusted OR =0.372, 95% CI =0.191-0.725). However, there was no association between genotype GT and risk of CRC (30.0% vs 28.0%, P=0.235, adjusted OR =1.210, 95% CI =0.903-1.548). Furthermore, genotype GT (P=0.003) and allele T (P=0.003) were significantly associated with poor differentiation, and genotypes GT and TT and allele T were significantly associated with tumor-node-metastases stage III (P=0.001 for GT vs GG, P<0.001 for TT vs GG, and P<0.001 for T vs G) and node metastasis (P<0.001 for GT vs GG, P=0.001 for TT vs GG, and P<0.001 for T vs G), respectively. These findings indicated that allele T and genotypes TT and GT/TT of rs712 might be susceptible factors for CRC, and mutated allele and genotypes of the locus might predict a poor clinical outcome in Chinese population. PMID- 26543375 TI - Combined olaparib and oxaliplatin inhibits tumor proliferation and induces G2/M arrest and gamma-H2AX foci formation in colorectal cancer. AB - BACKGROUND: Poly (ADP-ribose) polymerase 1 (PARP1) has an important role in homologous recombination repair. The purpose of this study was to investigate the effect of PARP1 inhibitor on oxaliplatin treatment for colorectal cancer (CRC). METHODS: A cell counting kit-8 assay was used to determine the sensitivity of CRC cells to olaparib and/or oxaliplatin. The gene and protein expressions of PARP1 and the gamma histone variant H2AX (gammaH2AX) were measured by real-time quantitative polymerase chain reaction and western blotting, respectively. The gammaH2AX foci formation assay was used to investigate the influence of treatments on cells. Flow cytometry was used to examine the changes in cell cycle distribution. Finally, we investigated the combination of olaparib and oxaliplatin in the CRC tumor model. RESULTS: Olaparib changed the expression of gammaH2AX and PARP1, and increased the sensitivity of CRC cells to oxaliplatin. The gammaH2AX foci assay showed that olaparib did not induce double-strand breaks (DSBs) alone, but it enhanced the induction of DSBs by oxaliplatin. The flow cytometry results showed that cells exposed to combination treatment had more G2/M-phase cells than control. Additionally, tumor xenograft studies suggested that combined treatment inhibited the growth of CRC. CONCLUSION: CRC cells are sensitized to combined treatment with olaparib and oxaliplatin, and this could be a promising strategy for clinical chemotherapy in CRC. PMID- 26543376 TI - Transarterial oily chemoembolization with lidamycin shows potent therapeutic efficacy in VX2 rabbit liver tumor. AB - Transarterial oily chemoembolization (TOCE) is one of the most effective approaches for the treatment of patients with hepatocellular carcinoma (HCC), who are not suitable for surgical therapy. Lidamycin (LDM), a potent antitumor antibiotic, demonstrates good antitumor efficacy in various tumor types, both in vitro and in vivo. In this study, the antitumor efficacy of LDM combined with TOCE against the rabbit VX2 tumor was assessed. A toxicity assay with 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) demonstrated that a combination of LDM with lipiodol did not impair the cytotoxicity of LDM against HepG2 cells in vitro. Using TOCE in rabbit VX2 tumor models, LDM showed a more powerful inhibitory effect against the tumor and lowered the expression levels of proliferating cell nuclear antigen (PCNA), cluster of differentiation 31 (CD31), and vascular endothelial growth factor (VEGF) compared to Adriamycin (ADM); moreover, this improvement was not accompanied by an increase of hepatotoxicity as shown by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. These results suggested that LDM combined with TOCE may be a feasible strategy in HCC therapy in the future. PMID- 26543377 TI - Concurrent chemoradiotherapy using paclitaxel plus cisplatin in the treatment of elderly patients with esophageal cancer. AB - OBJECTIVE: This study aimed at assessing the efficiency and safety of concurrent chemoradiotherapy (CCRT) using paclitaxel (PTX) plus cisplatin (CDDP) in elderly (age >=70 years) esophageal cancer patients. PATIENTS AND METHODS: Between July 2008 and June 2011, 82 esophageal cancer patients aged >=70 years were retrospectively analyzed. Chemotherapy consisted of CDDP for 3 days plus PTX given for 3 hours. The preplanned total dose of concurrent irradiation with 60 Gy/30 Fx was given at the 1st day of chemotherapy. RESULTS: The average age for the enrolled patients was 76.41 years (range: 70-87 years), and the clinical stages were stage I (two patients), stage II (23 patients), stage III (49 patients), and stage IV (eight patients). A total of 66 patients finished CCRT on schedule, including 55 (67.1%) patients in whom treatment regimen was not changed, and the clinical complete response was achieved in 29 patients. With a median follow-up time of 20.4 months, the median overall survival (OS) time and progression-free survival (PFS) time were 26.9 months and 18.2 months, respectively. The 2-year OS and PFS rates for stage I-II and III-IV were 76.0%, 64.0% and 38.6%, 21.2%, respectively. Grade >=3 leukopenia was observed in 25 patients, and the most common nonhematologic toxicity was esophagitis including five and two patients with grade 3 and 4, respectively. Multivariate analysis revealed that clinical stage was a strong factor for OS and PFS. CONCLUSION: CCRT using PTX plus CDDP for selected elderly esophageal cancer patients resulted in encouraging survival outcomes and tolerable toxicities. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report. PMID- 26543378 TI - Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells. AB - PURPOSE: Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands. METHODS: Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity. RESULTS: Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells. CONCLUSION: These data indicate that treatment with chNKG2D expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis. PMID- 26543379 TI - Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta analysis. AB - Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS) was then reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17-1.83, P=0.0001). The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16-0.86, P=0.02) and tumor size >5 cm (OR 0.48, 95% CI 0.26-0.88, P=0.02). In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. PMID- 26543380 TI - Serum dickkopf-1 as a biomarker in screening gastrointestinal cancers: a systematic review and meta-analysis. AB - OBJECTIVE: Despite advances in the early diagnosis of gastrointestinal (GI) cancers, these cancers are often being detected rather late in their course. Emerging published data on the accuracy of dickkopf-1 (DKK1) for diagnosing GI cancers are inconsistent. The purpose of this systematic review and meta-analysis was to evaluate the diagnostic value of DKK1 in the diagnosis of GI cancers. METHODS: A systematic literature search of PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and WANFANG databases was conducted to identify the related studies published before May 1, 2015, which investigated the diagnostic value of serum DKK1 for GI cancers. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2 checklist. The diagnostic performance was pooled and analyzed using a bivariate model. Publication bias was evaluated with the Deeks' funnel test. RESULTS: A total of 15 studies with 5,076 participants were finally identified for the meta-analysis. The pooled results of sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for DKK1 test were 0.72 (95% confidence interval [CI]: 0.70-0.74), 0.90 (95% CI: 0.89-0.91), 7.72 (95% CI: 4.90-12.14), 0.29 (95% CI: 0.22-0.39), and 28.95 (95% CI: 16.25-51.65) for diagnosis of GI cancers, respectively. The area under the summary receiver-operating characteristic curve was 0.8901. The SEN of DKK1 in diagnosis of gastric cancer and pancreatic cancer may be higher than hepatocellular carcinoma, and the SPE in pancreatic cancer subgroup was lower than hepatocellular carcinoma and gastric cancer subgroups. CONCLUSION: The currently available evidence suggests that serum DKK1 is a potential biomarker with high SEN and SPE for screening GI cancers. To better elucidate the usefulness of serum DKK1, further studies are needed. PMID- 26543381 TI - Management of pemphigus vulgaris: challenges and solutions. AB - The main objective in the treatment of pemphigus vulgaris is to control the disease, prevent relapses, and avoid adverse events associated with the prolonged use of steroids and immunosuppressive agents. Systemic corticosteroids remain the gold standard treatment for pemphigus vulgaris. Azathioprine and mycophenolate mofetil are the first line of steroid-sparing treatment. Rituximab is extremely effective in recalcitrant pemphigus, when other treatments fail to control the disease. The European Dermatology Forum recommends tapering prednisolone by 25% every 2 weeks after the consolidation phase, and a 5 mg reduction every 4 weeks when the dose is reduced to <20 mg. If the patient relapses, options include increasing steroids back to the previous dose, adding an immunosuppressant if using steroid monotherapy, or replacing a first-line immunosuppressant by another if already on combination therapy. PMID- 26543383 TI - Randomized comparative trial of cervical block protocols for pain management during hysteroscopic removal of polyps and myomas. AB - PURPOSE: To evaluate the efficacy of two cervical block protocols for pain management during hysteroscopic removal of intrauterine polyps and myomas using the MyoSure((r)) device. PATIENTS AND METHODS: This was a randomized, comparative treatment trial conducted by five private Obstetrics and Gynecology practices in the USA. Forty premenopausal women aged 18 years and older were randomized to receive either a combination para/intracervical block protocol of 37 cc local anesthetic administered at six injections sites in association with the application of topic 1% lidocaine gel, or an intracervical block protocol of 22 cc local anesthetic administered at three injections sites without topical anesthetic, for pain management during hysteroscopic removal of intrauterine polyps and/or a single type 0 or type 1 submucosal myoma <=3 cm. The main outcomes were a composite measure of procedure-related pain and pain during the postoperative recovery period, assessed by the Wong-Baker Faces Rating Scale (0= no pain to 10= maximum pain). The lesion characteristics, procedure time, and adverse events were summarized. RESULTS: A total of 17 polyps and eight myomas were removed in the para/intracervical block group, with diameters of 1.3+/-0.5 cm and 1.8+/-0.8 cm, respectively. In the intracervical block group, 25 polyps with a mean diameter of 1.2+/-0.7 cm and 7 myomas with a mean diameter of 1.9+/ 0.9 cm were removed. The mean tissue resection time was 1.2+/-2.0 minutes and 1.2+/-1.4 minutes for the para/intracervical and intracervical block groups, respectively. The mean composite procedure-related pain score was low for both cervical block protocols, 1.3+/-1.4 in the para/intracervical block group vs 2.1+/-1.5 in the intracervical block group. During the postoperative recovery period, the mean pain scores were 0.3+/-0.7 vs 1.2+/-1.7 for the para/intracervical and intracervical block groups, respectively. There were no serious adverse events. CONCLUSION: The MyoSure procedure for removal of polyps and myomas was well tolerated, with low pain scores reported for both the para/intracervical and intracervical block protocols. PMID- 26543382 TI - Exercise after breast cancer treatment: current perspectives. AB - Over the past 2 decades, great strides have been made in the field of exercise oncology research, particularly with breast cancer. This area of research is particularly important since there are >2.8 million breast cancer survivors who are in need of an intervention that can offset treatment-related side effects. Noticeable reductions in physical fitness (ie, cardiopulmonary fitness and muscular strength), negative changes in body composition (ie, increase in body mass, decrease in lean body mass, and increase in fat mass), increased fatigue, depression, or anxiety are some of the common side effects of cancer treatments that negatively impact overall quality of life and increase the risk for the development of comorbidities. Exercise plays a vital role in improving cardiopulmonary function, psychological events, muscular strength, and endurance in breast cancer survivors, and thus should be considered as a key factor of lifestyle intervention to reverse negative treatment-related side effects. The purpose of this review is to address current perspectives on the benefits of aerobic and resistance exercise after breast cancer treatments. This review is focused on the well-established benefits of exercise on physical and emotional well-being, bone health, lymphedema management, and the postulated benefits of exercise on risk reduction for recurrence of breast cancer. PMID- 26543384 TI - Sleep characteristics of individuals with chronic stroke: a pilot study. AB - Changes in sleep characteristics in individuals with chronic stroke are not well described, particularly compared with healthy individuals. Therefore, the aim of this pilot study was to explore the sleep characteristics in individuals with chronic stroke compared to age- and sex-matched controls. Sixteen individuals with chronic stroke and ten age- and sex-matched controls underwent two nights of polysomnographic recording. The sleep characteristics of interest included total sleep time, sleep efficiency, and percent time, as well as time in minutes spent in stages N1, N2, and N3 and stage R sleep. The individuals with chronic stroke spent less percent time in stage N3 compared with controls (P=0.048). No significant differences in the other sleep characteristics were found between the stroke and control groups. Individuals with chronic stroke present with altered stage N3 sleep compared with healthy controls. These alterations in stage N3 sleep might be a sign of neuronal dysfunction and may impact recovery following stroke. A larger scale study is needed to confirm these findings. PMID- 26543385 TI - Biomarkers of Angiogenesis in Colorectal Cancer. AB - Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for 10% of all new cancer diagnoses. Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Given the widespread use of antiangiogenic agents in CRC, there has been considerable interest in the development of methods to identify novel markers that can predict outcome in the treatment of this disease with angiogenesis inhibitors. Multiple biomarkers are in various phases of development and include tissue, serum, and imaging biomarkers. The complexity of the angiogenesis pathway and the overlap between the various angiogenic factors present a significant challenge to biomarker discovery. In our review, we discuss the angiogenesis pathway and the most promising evolving concepts in biomarker discovery, as well as highlight the landmark studies that identify subgroups of patients with CRC who may preferentially benefit from angiogenesis inhibitors. PMID- 26543388 TI - Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4. AB - Maturity onset diabetes of the young (MODY) is a rare form of diabetes mellitus typically seen in young adults that results from pancreatic beta-cell dysfunction. MODY4 is a rare subtype caused by a PDX1 mutation. In this case, we present a nonobese 26-year-old male with polyuria and polydipsia. Lab work showed a blood glucose of 511 mg/dL, no ketones or antibodies (insulin, islet cell, and glutamic acid decarboxylase [GAD]), C-peptide of 1.6 ng/mL, and A1c 9.3%. Genetic analysis revealed a novel nonsense mutation in the PDX1 gene, consistent with MODY type 4. Given this patient's particular genetic mutation affecting the incretin pathway, sitagliptin was substituted for glyburide, which led to significant improvement in glycemic control. Our case report identifies a unique mutation in a rare form of MODY and outlines management of ensuing diabetes through targeting its inherent genetic mutation. PMID- 26543386 TI - Development of hypertension in overweight adolescents: a review. AB - The upward trend in adolescent hypertension is widely attributed to the adolescent obesity epidemic. Secular trends in adolescent prehypertension and hypertension have risen in congruence with increasing trends in the prevalence of overweight and obesity. The correlation between body mass index and blood pressure in adolescence is moderate to strong in most studies and strongest in those classified as overweight or obese. The mechanisms relating to the development of hypertension in overweight adolescents are unclear; however, a number of nonmodifiable and modifiable factors have been implicated. Importantly, certain clinical and biochemical markers in overweight adolescents are indicative of high risk for hypertension, including family history of hypertension and hyperinsulinemia. These characteristics may prove useful in stratifying overweight adolescents as high or low risk of comorbid hypertension. The treatment of overweight and obesity related hypertension in this population focuses on two key modalities: lifestyle change and pharmacotherapy. These approaches focus almost exclusively on weight reduction; however, a number of emerging strategies target hypertension more specifically. Among adolescents with overt hypertension there are also several factors that indicate higher risk of concurrent subclinical disease, persistent adult hypertension, and adult cardiovascular disease. This group may benefit substantially from more aggressive pharmacological treatments. Limitations in the literature relate to the paucity of studies reporting specific effects for the adolescent age group of overweight and obese individuals. Nonetheless, intervention for adiposity-related hypertension in adolescence may partially mitigate some of the cardiovascular risk in adulthood. PMID- 26543387 TI - Organizing Pneumonia in Rheumatoid Arthritis Patients: A Case-Based Review. AB - We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients. PMID- 26543390 TI - Epidemiological Survey of Severe Fever with Thrombocytopenia Syndrome Virus in Ticks in Nagasaki, Japan. AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease endemic in East Asia. Transmitted to other organisms by infected ticks, the SFTS virus (SFTSV) and is endemic to Nagasaki in western Japan. However, epidemiological information regarding SFTSV in Nagasaki ticks has not been available to date. In this study, we began by examining the sensitivities of SFTSV gene detection by real-time RT-PCR and virus isolation in cultured cells and mice. These methods could detect SFTSV in the samples containing more than 4 * 10(0) ffu. Next, we attempted to isolate SFTSV and to detect viral gene in 2,222 nymph and adult ticks collected from May to August 2013 among seven regions of Nagasaki. However, neither virus isolation nor viral gene detection were confirmed in the tick pools. SFTSV positivity rates are considered to be very low in ticks, and viral loads are also very limited. Further investigations increasing the number of ticks and including larval samples as well as improved detection methods, may be required to find SFTSV-positive ticks in this region. PMID- 26543389 TI - Emerging drugs of abuse: current perspectives on synthetic cannabinoids. AB - New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs). SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as "herbal smoking blends" or "herbal incense" under brand names like "Spice" or "K2". Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. PMID- 26543391 TI - Republication: Two Premature Neonates of Congenital Syphilis with Severe Clinical Manifestations. AB - Congenital syphilis (CS) is a public health burden in both developing and developed countries. We report two cases of CS in premature neonates with severe clinical manifestations; Patient 1 (gestational age 31 weeks, birth weight 1423 g) had disseminated idiopathic coagulation (DIC) while Patient 2 (gestational age 34 weeks and 6 days, birth weight 2299 g) had refractory syphilitic meningitis. Their mothers were single and had neither received antenatal care nor undergone syphilis screening. Both neonates were delivered via an emergency cesarean section and had birth asphyxia and transient tachypnea of newborn. Physical examination revealed massive hepatosplenomegaly. Laboratory testing of maternal and neonatal blood showed increased rapid plasma reagin (RPR) titer and positive Treponema pallidum hemagglutination assay. Diagnosis of CS was further supported by a positive IgM fluorescent treponemal antibody absorption test and large amounts of T. pallidum spirochetes detected in the placenta. Each neonate was initially treated with ampicillin and cefotaxime for early bacterial sepsis/meningitis that coexisted with CS. Patient 1 received fresh frozen plasma and antithrombin III to treat DIC. Patient 2 experienced a relapse of CS during initial antibiotic treatment, necessitating parenteral penicillin G. Treatment was effective in both neonates, as shown by reductions in RPR. Monitoring of growth and neurological development through to age 4 showed no evidence of apparent delay or complications. Without adequate antenatal care and maternal screening tests for infection, CS is difficult for non-specialists to diagnose at birth, because the clinical manifestations are similar to those of neonatal sepsis and meningitis. Ampicillin was insufficient for treating CS and penicillin G was necessary. PMID- 26543392 TI - Comparative Study of Paired Serum and Cerebrospinal Fluid Samples from Neurocysticercosis Patients for the Detection of Specific Antibody to Taenia solium Immunodiagnostic Antigen. AB - Neurocysticercosis (NCC) is an important disease of the central nervous system caused by infection with Taenia solium metacestodes. In addition to the clinical findings and the imaging analysis, the results of immunological tests are informative for the diagnosis of NCC. To compare the usefulness of serum and cerebrospinal fluid (CSF) samples for antibody detection, paired serum and CSF samples from patients with NCC and other neurological diseases were examined by an enzyme-linked immunosorbent assay with low-molecular-weight antigens purified from T. solium cyst fluid in a blinded fashion. The sensitivity of both serum and CSF samples was 25.0% in inactive NCC cases (n = 4) and 90.9% in active NCC cases (n = 33), and the specificity of serum and CSF was 100% and 95.8%, respectively. When the serum and CSF samples were combined, the sensitivity in active NCC cases became 100%. There was no difference in test performance between serum and CSF samples. Based on these results, we recommend the detection of specific antibodies in serum for the diagnosis of active NCC because of the ease of collection. When the antibody test is negative, however, CSF should be used to confirm NCC and to rule out other medical disorders of the central nervous system. Antibody detection test using only serum or CSF has a limited diagnostic value and cannot be recommended for the diagnosis of suspected inactive NCC cases. PMID- 26543393 TI - An Early Detection of Decline in Rotavirus Cases during the 2013/2014 Season in Japan as Revealed by Time-series Analysis of National Surveillance Data. AB - Rotavirus is a leading cause of severe acute gastroenteritis in children worldwide, and globally licensed vaccines are available. To expedite the introduction of rotavirus vaccines in the national immunisation programme, a simple, ecological method to monitor changes in the burden of rotavirus disease may be of great help. Here, we report an application of a time-series analysis on a publicly-available dataset in Japan on the weekly number of laboratory confirmed rotavirus-positive samples over the last 5 year period between the 36th week of 2009 and the 35th week of 2014 during which rotavirus vaccines became marketed in Japan and presumed to reach an uptake rate of at least 39% as a national average. Compared with the expected number of rotavirus detection based on the preceding four rotavirus seasons, the number of rotavirus detection during the 2013-2014 season was 42.9% (95% CI: 38.6, 47.8). This suggests that the use of rotavirus vaccine had a positive impact on reducing the burden of rotavirus diarrhoea in Japan. This method, because of its simplicity and little cost, should be applicable to early detection of the impact of rotavirus vaccine even in resource-poor countries where the World Health Organization funded and implemented the sentinel surveillance programmes of laboratory-confirmed rotavirus cases. PMID- 26543394 TI - Bacteriological Profile and Antibiotic Susceptibility Pattern of Neonatal Sepsis at a Teaching Hospital in Bayelsa State, Nigeria. AB - BACKGROUND: Sepsis is one of the most common causes of neonatal hospital admissions and is estimated to cause 26% of all neonatal deaths worldwide. While waiting for results of blood culture, it is necessary to initiate an empirical choice of antibiotics based on the epidemiology of causative agents and antibiotic sensitivity pattern in a locality. OBJECTIVE: To determine the major causative organisms of neonatal sepsis at the Niger Delta University Teaching Hospital (NDUTH), as well as their antibiotic sensitivity patterns, with the aim of formulating treatment protocols for neonates. METHODS: Within a 27-month period (1st of October 2011 to the 31st of December 2013), results of blood culture for all neonates screened for sepsis at the Special Care Baby Unit of the hospital were retrospectively studied. RESULTS: Two hundred and thirty-three (49.6%) of the 450 neonates admitted were screened for sepsis. Ninety-seven (43.5%) of them were blood culture positive, with 52 (53.6%) of the isolated organisms being Gram positive and 45 (46.4%) Gram negative. The most frequently isolated organism was Staphylococcus aureus (51.5%) followed by Escherichia coli (16.5%) and Klebsiella pneumoniae (14.4%). All isolated organisms demonstrated the highest sensitivity to the quinolones. CONCLUSION: Neonatal sepsis is a significant cause of morbidity among neonates admitted at the NDUTH. There is a need for regular periodic surveillance of the causative organisms of neonatal sepsis as well as their antibiotic susceptibility pattern to inform the empirical choice of antibiotic prescription while awaiting blood culture results. PMID- 26543395 TI - Management of Severe Gastrointestinal Tuberculosis with Injectable Antituberculous Drugs. AB - Abdominal tuberculosis (TB) is generally responsive to medical treatment, and early diagnosis and management can prevent unnecessary surgical intervention. However, intravenous therapy is needed for severe forms of tuberculosis with extensive gastrointestinal involvement. The authors report an immunocompetent patient with gastrointestinal TB who was successfully managed with a combination of surgical intervention and anti-TB medications, and discuss the importance of injectable anti-TB medications in the management of severe gastrointestinal TB. The present case report provides a model for assessment and intervention in severe forms of gastrointestinal TB. PMID- 26543396 TI - The Use of Ozone in High Frequency Device to Treat Hand Ulcers in Leprosy: a Case Study. AB - Leprosy leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Autonomic dysfunctions may result in dryness and cracking of the skin. In this study, we present the use of ozone provided by a high-frequency device to treat hand ulcers (wounds) in an 80-year-old man who was diagnosed as multibacillary in 2007. In the first visit, the patient was evaluated and received verbal and written instructions about self care. Treatment consisted of five sessions, once per week. The ozone provided by a high-frequency device seemed to be useful in the treatment of ulcers, thus, contributing to the healing process. Research that investigates the use of high frequencies in the treatment of ulcers associated or not with other interventions (self-care strategies, protective clothing, adapted tools and footwear adaptation) is strongly recommended. PMID- 26543397 TI - On the concept of sloped motion for free-floating wave energy converters. AB - A free-floating wave energy converter (WEC) concept whose power take-off (PTO) system reacts against water inertia is investigated herein. The main focus is the impact of inclining the PTO direction on the system performance. The study is based on a numerical model whose formulation is first derived in detail. Hydrodynamics coefficients are obtained using the linear boundary element method package WAMIT. Verification of the model is provided prior to its use for a PTO parametric study and a multi-objective optimization based on a multi-linear regression method. It is found that inclining the direction of the PTO at around 50 degrees to the vertical is highly beneficial for the WEC performance in that it provides a high capture width ratio over a broad region of the wave period range. PMID- 26543398 TI - Antiplane wave scattering from a cylindrical cavity in pre-stressed nonlinear elastic media. AB - The effect of a longitudinal stretch and a pressure-induced inhomogeneous radial deformation on the scattering of antiplane elastic waves from a cylindrical cavity is determined. Three popular nonlinear strain energy functions are considered: the neo-Hookean, the Mooney-Rivlin and a two-term Arruda-Boyce model. A new method is developed to analyse and solve the governing wave equations. It exploits their properties to determine an asymptotic solution in the far-field, which is then used to derive a boundary condition to numerically evaluate the equations local to the cavity. This method could be applied to any linear ordinary differential equation whose inhomogeneous coefficients tend to a constant as its independent variable tends to infinity. The effect of the pre stress is evaluated by considering the scattering cross section. A longitudinal stretch is found to decrease the scattered power emanating from the cavity, whereas a compression increases it. The effect of the pressure difference depends on the strain energy function employed. For a Mooney-Rivlin material, a cavity inflation increases the scattered power and a deflation decreases it; for a neo Hookean material, the scattering cross section is unaffected by the radial deformation; and for a two-term Arruda-Boyce material, both inflation and deflation are found to decrease the scattered power. PMID- 26543399 TI - Fluorescence-tagged metallothionein with CdTe quantum dots analyzed by the chip CE technique. AB - ABSTRACT: Quantum dots (QDs) are fluorescence nanoparticles (NPs) with unique optic properties which allow their use as probes in chemical, biological, immunological, and molecular imaging. QDs linked with target ligands such as peptides or small molecules can be used as tumor biomarkers. These particles are a promising tool for selective, fast, and sensitive tagging and imaging in medicine. In this study, an attempt was made to use QDs as a marker for human metallothionein (MT) isoforms 1 and 2. Four kinds of CdTe QDs of different sizes bioconjugated with MT were analyzed using the chip-CE technique. Based on the results, it can be concluded that MT is willing to interact with QDs, and the chip-CE technique enables the observation of their complexes. It was also observed that changes ranging roughly 6-7 kDa, a value corresponding to the MT monomer, depend on the hydrodynamic diameters of QDs; also, the MT sample without cadmium interacted stronger with QDs than MT saturated with cadmium. Results show that MT is willing to interact with smaller QDs (blue CdTe) rather than larger ones QDs (red CdTe). To our knowledge, chip-CE has not previously been applied in the study of CdTe QDs interaction with MT. GRAPHICAL ABSTRACT: PMID- 26543400 TI - Supersymmetric dark matter after LHC run 1. AB - Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, [Formula: see text], assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau [Formula: see text], stop [Formula: see text] or chargino [Formula: see text], resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a larger Higgsino component of the LSP in the focus point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the [Formula: see text] coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for [Formula: see text] events and long-lived charged particles, whereas their H / A funnel, focus-point and [Formula: see text] coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. We find that the dominant DM mechanism in our pMSSM10 analysis is [Formula: see text] coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches. PMID- 26543405 TI - Biotechnological Uses of Archaeal Proteins. PMID- 26543404 TI - Lepton flavour violating top decays at the LHC. AB - We consider lepton-flavour violating decays of the top quark, mediated by 4 fermion operators. We compile constraints on a complete set of SU(3) [Formula: see text] U(1)-invariant operators, arising from their loop contributions to rare decays and from HERA's single-top search. The bounds on e-[Formula: see text] flavour change are more restrictive than on [Formula: see text]-[Formula: see text]; nonetheless the top could decay to a jet [Formula: see text] with a branching ratio of order [Formula: see text]. We estimate that the currently available LHC data (20 fb[Formula: see text] at 8 TeV) could be sensitive to [Formula: see text]+ jet) [Formula: see text], and we extrapolate that 100 fb[Formula: see text] at 13 TeV could reach a sensitivity of [Formula: see text]. PMID- 26543403 TI - Renormalization scheme dependence of the two-loop QCD corrections to the neutral Higgs-boson masses in the MSSM. AB - Reaching a theoretical accuracy in the prediction of the lightest MSSM Higgs boson mass, [Formula: see text], at the level of the current experimental precision requires the inclusion of momentum-dependent contributions at the two loop level. Recently two groups presented the two-loop QCD momentum-dependent corrections to [Formula: see text] (Borowka et al., Eur Phys J C 74(8):2994, 2014; Degrassi et al., Eur Phys J C 75(2):61, 2015), using a hybrid on-shell [Formula: see text] scheme, with apparently different results. We show that the differences can be traced back to a different renormalization of the top-quark mass, and that the claim in Ref. Degrassi et al. (Eur Phys J C 75(2):61, 2015) of an inconsistency in Ref. Borowka et al. (Eur Phys J C 74(8):2994, 2014) is incorrect. We furthermore compare consistently the results for [Formula: see text] obtained with the top-quark mass renormalized on-shell and [Formula: see text]. The latter calculation has been added to the FeynHiggs package and can be used to estimate missing higher-order corrections beyond the two-loop level. PMID- 26543402 TI - The pMSSM10 after LHC run 1. AB - We present a frequentist analysis of the parameter space of the pMSSM10, in which the following ten soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale [Formula: see text]: the gaugino masses [Formula: see text], the first-and second-generation squark masses [Formula: see text], the third-generation squark mass [Formula: see text], a common slepton mass [Formula: see text] and a common trilinear mixing parameter A, as well as the Higgs mixing parameter [Formula: see text], the pseudoscalar Higgs mass [Formula: see text] and [Formula: see text], the ratio of the two Higgs vacuum expectation values. We use the MultiNest sampling algorithm with [Formula: see text]1.2 [Formula: see text] points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly interacting sparticle masses of ATLAS and CMS searches for jets, leptons [Formula: see text][Formula: see text] signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for electroweakly interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements of [Formula: see text] by LHCb and CMS, other B-physics observables, electroweak precision observables, the cold dark matter density and the XENON100 and LUX searches for spin-independent dark matter scattering, assuming that the cold dark matter is mainly provided by the lightest neutralino [Formula: see text]. We show that the pMSSM10 is able to provide a supersymmetric interpretation of [Formula: see text], unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum [Formula: see text] with 18 degrees of freedom (d.o.f.) in the pMSSM10, corresponding to a [Formula: see text] probability of 30.8 %, to be compared with [Formula: see text] in the CMSSM (NUHM1) (NUHM2). We display the one-dimensional likelihood functions for sparticle masses, and we show that they may be significantly lighter in the pMSSM10 than in the other models, e.g., the gluino may be as light as [Formula: see text]1250 [Formula: see text] at the 68 % CL, and squarks, stops, electroweak gauginos and sleptons may be much lighter than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, [Formula: see text] colliders and direct detection experiments. PMID- 26543407 TI - Institutions and national development in Latin America: a comparative study. AB - We review the theoretical and empirical literatures on the role of institutions on national development as a prelude to present a more rigorous and measurable definition of the concept and a methodology to study this relationship at the national and subnational levels. The existing research literature features conflicting definitions of the concept of "institutions" and empirical tests based mostly on reputational indices, with countries as units of analysis. The present study's methodology is based on a set of five strategic organizations studied comparatively in five Latin American countries. These include key federal agencies, public administrative organizations, and stock exchanges. Systematic analysis of results show a pattern of differences between economically-oriented institutions and those entrusted with providing basic services to the general population. Consistent differences in institutional quality also emerge across countries, despite similar levels of economic development. Using the algebraic methods developed by Ragin, we test six hypotheses about factors determining the developmental character of particular institutions. Implications of results for theory and for methodological practices of future studies in this field are discussed. PMID- 26543406 TI - Production and Application of a Soluble Hydrogenase from Pyrococcus furiosus. AB - Hydrogen gas is a potential renewable alternative energy carrier that could be used in the future to help supplement humanity's growing energy needs. Unfortunately, current industrial methods for hydrogen production are expensive or environmentally unfriendly. In recent years research has focused on biological mechanisms for hydrogen production and specifically on hydrogenases, the enzyme responsible for catalyzing the reduction of protons to generate hydrogen. In particular, a better understanding of this enzyme might allow us to generate hydrogen that does not use expensive metals, such as platinum, as catalysts. The soluble hydrogenase I (SHI) from the hyperthermophile Pyrococcus furiosus, a member of the euryarchaeota, has been studied extensively and used in various biotechnological applications. This review summarizes the strategies used in engineering and characterizing three different forms of SHI and the properties of the recombinant enzymes. SHI has also been used in in vitro systems for hydrogen production and NADPH generation and these systems are also discussed. PMID- 26543408 TI - E-selectin and vascular cell adhesion molecule-1 as biomarkers of 3-month outcome in cerebrovascular diseases. AB - BACKGROUND: Inflammation is known to worsen cerebral damage at the acute phase of stroke. In this setting, cell adhesion molecules (CAMs) play a crucial role mediating migration of immune cells into the infarcted area. However, their value in long-term outcome prediction for patients with cerebrovascular diseases (CVD) is less described. METHODS: Levels of four CAMs (E-selectin, P-selectin glycoprotein ligand-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1)) and six other known biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT proBNP), troponin I, vasopressin-neurophysin 2-copeptin, and S100 calcium-binding protein B) were measured in a population of patients presenting CVD. Blood collections for analysis were performed within different time windows after stroke onset: 0-6 h, 6-36 h, 2-3 days, 5-7 days, and 2-3 weeks. Independent associations with poor outcome at 3 months (modified Rankin Scale score > 2) were sought using univariate and multivariate analysis after adjustments for age and National Institute of Health Stroke Scale score. Predictive ability of each biomarker has also been assessed with ROC analysis. RESULTS: One hundred patients were prospectively included whom 75 presented with ischemic strokes, nine with hemorrhagic strokes and 16 with transient ischemic attacks. During the first 6 h after stroke onset, E-selectin was found to be an independent predictor of 3 month outcome (odds ratio (OR) =24; 95 % confidence interval (95 % CI), 2-354; p = 0.022) (area under the curve (AUC) =78 %), as was VCAM-1 during the third week after onset (OR = 8; 95 % CI, 2-37; p = 0.01) (AUC = 73 %). Associations remained after the exclusion of patients with hemorrhagic strokes and transient ischemic attacks. Independent associations with outcome were also found for CRP (OR = 5; 95 % CI, 1-22; p = 0.023) and IL-6 (OR = 5; 95 % CI, 1-17; p = 0.021) at 2-3 days and for NT-proBNP at 6-36 h (OR = 20; 95 % CI, 1-337; p = 0.04). CONCLUSIONS: E selectin and VCAM-1 were independent predictors of outcome in a population of patients with CVD. The predictive capability of other biomarkers known to be indicators for prognosis also emerged, confirming the study's robustness. CAMs levels could be considered as objective biological criteria for prognosis in CVD. PMID- 26543409 TI - Patient's Satisfaction with Health Care: a Questionnaire Study of Different Aspects of Care. AB - AIM: To determine the influence of sociodemographic factors on patients' satisfaction with health care system. METHODS: In a cross-sectional study, 1,995 patients from 12 municipalities of Zenica-Doboj Canton were interviewed after a visit to the practice. Individual interviews were conducted and the questionnaire was made on the basis of EUROPEP (European Task Force on Patient Evaluations of General Practice Care) standardized questionnaire. RESULTS: Out of the total number patients, 47.1% were females, 47.9% were from urban population and median of age was 42.0 years (IQR = 30.0 to 53.0 years). The rural population was more likely to buy drugs for medical treatment (p < 0.001) and parenteral injections in primary care practice (p < 0.001). Patients with lower level of education were more likely: to be ordered for physical examination (p = 0.001), to buy drugs for medical treatment (p = 0.001), to buy parenteral injections in primary care practice (p < 0.001); to pay unofficially to someone from medical staff (p < 0.001); to feel that they could be better treated (p = 0.032) and they had longer waiting for health service in primary care practice (p < 0.001). Older population had better assessment of secondary (p = 0.040) and tertiary health care practices (p = 0.034); needed more time is needed to reach health facilities (p = 0.016), longer waiting for health service in primary care practice (p < 0.001); more likely to have health problems in the past 12 months but they did not request medical treatment (p = 0.008); more likely to be ordered for physical examination (p < 0.001); more likely to buy drugs for medical treatment (p = 0.004); more likely to buy parenteral injections in primary care practice (p < 0.001). CONCLUSION: The following variables: gender, age, overall perception of health status and financial status appear to be predictors of patients' satisfaction. PMID- 26543410 TI - General Satisfaction Among Healthcare Workers: Differences Between Employees in Medical and Mental Health Sector. AB - BACKGROUND: General satisfaction is a personal experience and sources of satisfaction or dissatisfaction vary between professional groups. General satisfaction is usually related with work settings, work performance and mental health status. AIM: The purpose of this research study was to investigate the level of general satisfaction of health care workers and to examine whether there were any differences among employees of medical and mental health sector. METHODS: The sample consisted of employees from the medical and mental health sector, who were all randomly selected. A two-part questionnaire was used to collect data. The first section involved demographic information and the second part was a General Satisfaction Questionnaire (GSQ). The statistical analysis of data was performed using the software package 19.0 for Windows. Descriptive statistics were initially generated for sample characteristics. All data exhibited normal distributions and thus the parametric t-test was used to compare mean scores between the two health sectors. P values < 0.05 were defined as reflecting the acceptable level of statistical significance. RESULTS: 457 healthcare workers completed the questionnaire. The mean age of the sample was 41.8 +/- 7.9 years. The Cronbach alpha coefficient for GSQ was 0.79. The total mean score of general satisfaction for the employees in medical sector was 4.5 (5=very satisfied) and for the employees in mental health sector is 4.8. T-test showed that these results are statistical different (t=4.55, p<0.01) and therefore the two groups of healthcare workers feel different general satisfaction. CONCLUSIONS: Mental health employees appear to experience higher levels of general satisfaction and mainly they experience higher satisfaction from family roles, life and sexual life, emotional state and relations with patients. PMID- 26543412 TI - Predictive Role of Preventive Measures in Preventing the Progression of Diabetic Foot. AB - INTRODUCTION: Diabetes mellitus (DM) is one of the most common endocrine disease of modern life. Diabetic foot (DF) is the term for a foot of a patient suffering from DM with the potential risk of a number of pathological sequels, including infection, ulceration and/or destruction of deep tissue. GOAL: To determine the importance of preventive measures to prevent the development of diabetic foot. RESULTS: The gender structure of respondents categorized by the complication of DF (yes/no) was uniform. The average age was 60.15+/-12.2 years. Respondents without DF, 63% had 2 visits to the doctor a month, while in the group of those with DF, 39% of them had 3 visits to a doctor and 33% four or more times. Wearing comfortable shoes and foot hygiene in relation to the development of the DF are interdependent: c(2)=4,409; c(2) = 12.47 (p <0.0005). Also, recurrent foot injury, and slow healing of sores in comparison to the development of the DF are mutually dependent; c(2)=13,195; c(2)=14 (p <0.0005). CONCLUSION: We found that there is a significant statistical relationship between preventive measures and development of the DF. PMID- 26543411 TI - Impact of Educational Intervention on Patients Behavior with Smear-positive Pulmonary Tuberculosis: A Study Using the Health Belief Model. AB - INTRODUCTION: Tuberculosis is a single-agent infectious disease, which is the major cause of death around the world. Approximately one third of the world's population is infected with tuberculosis (TB) bacilli and at risk of developing active TB. The purpose of this study was determined the impact of education based on health belief model in promoting behavior of smear-positive pulmonary TB among patients in Chabahar city, Iran. MATERIAL AND METHODS: Of the 80 smear-positive pulmonary TB who referred to health centers in Chabahar voluntarily participated in this interventional study. The data collected using questionnaire based on health belief model. The data were analyzed by using paired t-test, independent t test, pearson correlation and chi-square test with SPSS 16. RESULTS: The cognitive skills were increased significantly from 6.10 to 6.88 after intervention. All behavioral skills were increased significantly from 2.08 to 2.88 after implementing the intervention. Perceived severity was increased from11.08to12.19 significantly. Percepted benefits were enhanced significantly from 11.48 to 12.23. Mean percepted barrier was decreased significantly from 17.52 to 16.68. CONCLUSION: Findings demonstrated that implementing educational intervention programs can increase the level of knowledge and behavior of patients regarding smear- positive pulmonary TB initiatives. PMID- 26543413 TI - Antiasthmatic Inhaled Medications as Favoring Factors for Increased Concentration of Streptococcus Mutans. AB - INTRODUCTION: The negative impact of inhaled antiasthmatic drugs (IAD) on oral health is reflected primarily in the increased incidence of caries in asthmatic children compared to healthy children. It is believed that one of the causes of the increased incidence of caries in asthmatic children is from bronchodilator effect in reduced secretion of saliva. Decreased salivation favors bacterial colonization and studies have shown that the concentration of Streptococcus mutans, a bacterium that has the primary role in the development of caries, is higher in asthmatic than in healthy children. MATERIAL AND METHODS: The study sample consisted of 200 patients, age from 7-14 years, divided into two groups: control group (n1 = 100) consisted of healthy children and the experimental group consisted of children suffering from asthma (n2 = 100). In both groups of respondents are identified the DMFT values, the concentration of Streptococcus mutans, the amount of stimulated saliva and plaque index value. RESULTS: It was found that there are significant differences in the values of plaque index, salivary index and streptococcus mutans between the control and experimental groups (p> 0.05 for each of the examined variables). Those in the control group had significantly higher DMFT index than subjects in the experimental group (p = 0.004). CONCLUSION: IAD does not cause reduced saliva production and thus do not represent a factor favoring increased concentration of Streptococcus mutans. PMID- 26543414 TI - Impact of the Tamsulosin in Alpha Adrenergic Receptor of Airways at Patients with Increased Bronchial Reactibility. AB - OBJECTIVE: In this work, effect of tamsulosin as antagonist of alpha1A and alpha1B adrenergic receptor and effect of agonists of beta2 adrenergic receptor salbutamol in patients with increased bronchial reactibility was studied. METHODS: Parameters of the lung function are determined with Body plethysmography six (6) hours after administration of tamsulosin. Raw and ITGV were registered and specific resistance (SRaw) was calculated as well. Tamsulosin was administered in per os manner as a preparation in the shape of the capsules with a brand name of "Prolosin", produced by Niche Generics Limited, Hitchin, Herts. RESULTS: After six (6) hours of administration of tamsulosin, results gained indicate that blockage of alpha1A and alpha1B-adrenergic receptor (0.8 mg per os) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in comparison to the check-up that has inhaled salbutamol agonist of adrenergic beta2 receptor (2 inh. x 0.2 mg), (p < 0.05). Blood pressure suffered no significant decrease following administration of the 0.8 mg dose of tamsulosin. CONCLUSION: This suggests that even after six hours of administration of tamsulosin, and determining of lung function parameters, the activity of alpha1A and alpha1B-adrenergic receptor in the smooth bronchial musculature has not changed in patients with increased bronchial reactibility. PMID- 26543415 TI - Grand Multiparity: Risk Factors and Outcome in a Tertiary Hospital: a Comparative Study. AB - AIM: The aim of the current study was to determine the prevalence of grand multiparity and the associated risks factors. METHODS: Four hundred thirty grandmutliparas (parity 5 or more) were compared with multiparous population (parity 2-4) with regard to maternal age, gestational age, mode of delivery, fetal and maternal outcomes and inter-current medical and obstetrical problems. RESULTS: There were significant association between grand multiparity and adverse pregnancy outcomes such as cesarean delivery (OR=2.699, CI=2.072-3.515, p<0.001), fetal macrosomia (OR=1.675; 95% CI=1.004- 2.796, p=.048), Diabetes mellitus (OR=1.634, 95%CI=1.076-2.481, p=0 .021), and pregnancy induced hypertension (OR=1.838, 95% CI=1.054-3.204, p= .032). No significant associations were seen in placenta abruption, placenta previa, preterm labor, postpartum hemorrhage and the frequency of admission to neonatal intensive care unit. No prenatal or maternal mortality was reported in this study. CONCLUSION: Grand multiparty remains a major obstetrics problem. It is associated with many medical and obstetrical complications. In communities where large family is desirable it is important to address the value of family planning and conduction of meticulous antenatal care. PMID- 26543416 TI - Doctors' Preferences for Controlled Ovarian Stimulation Protocols in Intrauterine Insemination. AB - INTRODUCTION: Intrauterine insemination (IUI) is an important treatment for infertility. IUI combined with controlled ovarian stimulation (COS) is widely used because of the higher pregnancy rates compared to IUI cycles without COS. MATERIAL AND METHODS: We retrospectively analyzed a single center data from 458 patients underwent the first IUI cycle and had only 1 mature follicle from May 2009 to January 20144. 48 cycles were performed with Clomiphene citrate/Letrozole (CC/LE), 244 cycles with gonadotropins (Gn), 71 cycles with CC/LE+Gn, and 95 cycles in NC group. RESULTS: Results showed that doctors preferred Gn protocol (53.3%) (p<0.05). Older patients were more likely to be allocated to CC/LE or NC group. 98.95% patients in NC group had regular menstruation cycle, with only 49.3% in CC/LE+Gn group (p<0.05). Estradiol (E2) level was much higher in COS groups than in NC group (p<0.05, for one mature follicle patients), and no significant differences were found within the COS groups. Duration of reaching follicles maturation was the shortest in Gn group and the longest in NC group, and NC group has the smallest follicular diameter (p<0.05). CONCLUSION: No significances were found regarding the IUI outcomes. To sum up, doctors prefer COS for IUI. Patients' age, menstruation cycle, infertile etiology and ovary function were the main factors affecting doctors' selection of COS protocols. PMID- 26543417 TI - Effect of Age, Educational Status, Parity and BMI on Development of Urinary Incontinence - a Cross Sectional Study in Saudi Population. AB - BACKGROUND: The research article looks at the background of women with urinary incontinence and exposed to different demographic factors. Women who had urinary incontinence and women without urinary incontinence were compared with regards to their demographic features and risk of development of urinary problems. These risk factors can either cause short term or temporary urinary incontinence or they can cause long term or permanent urinary incontinence. This article explores the association of age, educational status, body mass index (BMI) and parity on the development of urinary incontinence. AIM OF STUDY: This study aimed at conducting an analysis into the risk factors that are related to urinary incontinence. RESULTS AND ANALYSIS: Z-tests were conducted for every demographic factor and the results are then discussed comprehensively citing various studies that have been conducted before. Analysis shows that age and BMI increase chances of urinary infection and consequently urinary incontinence. Women of lower educational levels record more cases of urinary incontinence due to lack of general information about the condition. Women with higher parity levels also record more cases of urinary infections and subsequently urinary incontinence. CONCLUSION: From the analysis above, it can be seen that these factors usually play great roles in the existence and absence of urinary incontinence especially in women in Saudi Arabia. Most important is that, its prevention is mostly by use of the risk factors mentioned here in the research. This will usually involve observing a given risk factor to a state that makes it unfavorable for urinary incontinence to occur. PMID- 26543418 TI - Assessment of Symptoms in Cancer Patients Undergoing Chemotherapy in Northern Greece. AB - INTRODUCTION: Cancer patients experience a variety of symptoms that can be physical or psychological. These symptoms may vary in terms of occurrence, severity and distress and can be the result of the illness or the treatment. PURPOSE: The purpose of this study is to investigate the frequency, severity and distress of symptoms that chemotherapy induces in cancer patients. MATERIAL METHOD: This study included 200 cancer patients undergoing chemotherapy in a major city of Northern Greece. Data was collected using the Memorial Symptom Assessment Scale and Questionnaire, with demographic and clinical characteristics. RESULTS: The vast majority of those included in the sample were male participants (n=127, 63.5%). Their mean age was 58.95 (SD=9.95, range 29 79). The most prevalent physical symptoms were numbness/tingling in the hands/feet (54%), followed by lack of energy (46%). Feeling nervous (52%) and having trouble sleeping (41%) were the two most common psychological symptoms. CONCLUSIONS: The results of this study demonstrate that cancer patients undergoing chemotherapy experience various symptoms in high prevalence, and that they are quite severe. Therefore nurses should take into account these findings and plan appropriate, suitable care plans and interventions in order to alleviate them and improve patients' quality of life. PMID- 26543419 TI - Association of Body Weight and Body Mass Index with Bone Mineral Density in Women and Men from Kosovo. AB - BACKGROUND AND OBJECTIVE: Body weight and body mass index (BMI) are considered potentially modifiable determinants of bone mass. Therefore, the aim of this study was to explore the association between body weight and body mass index (BMI) with total hip and lumbar spine bone mineral density (BMD). METHODS: This cross-sectional study included a population of 100 women and 32 men from Kosovo into three BMI groups. All the study subjects underwent dual-energy X-ray absorptiometry (DXA) measurements. RESULTS: Total hip BMD levels of obese menopausal and premenopausal women and men were significantly higher compared to overweight or normal weight subjects, while lumbar spine BMD levels of only menopausal women and men were higher among obese subjects. Age-adjusted linear regression analysis showed that BMI is a significant independent associate of lumbar spine and total hip BMD in menopausal women and men. CONCLUSION: Despite positive association between BMI and lumbar spine and total hip BMD in menopausal women, presence of more obese and osteoporotic subjects among menopausal women represent a population at risk for fractures because of poor balance and frequent falls; therefore, both obesity and osteoporosis prevention efforts should begin early on in life. PMID- 26543420 TI - A Cross-sectional Study on the Prevalence of Physical Activity Among Primary Health Care Physicians in Aljouf Region of Saudi Arabia. AB - BACKGROUND: Sedentary life style and consequent obesity prevail in both developed and developing nations; gender- and age-independently. Physical inactivity in a population in a life style transition-like Saudi Arabia-causes metabolic syndrome with its immediate and long-term complications. Healthcare workers are in a better position for role modeling and counseling of appropriate health behaviors. Personal physical activity and body built among physicians influences to some degree their exercise counseling. Realizing such principle necessitates gauging the extent of physical activity among physicians and assessing the likelihood of counseling the patients on physical activities. METHODS: A cross-sectional study enrolled primary health care physicians (PHCPs) from primary health care centers and general hospitals of two cities (Sakaka and Dumat Al-Jandal) of Aljouf region, Saudi Arabia. Both genders were included. English version of step-wise questionnaire of World Health Organization was used for data collection. RESULTS: The response rate was 64.2%. 65.2% of respondent PHCPs were doing moderate to vigorous physical exercise and 34.8% of them were physically inactive. Majority of physically inactive PHCPs had intention to increase their physical activity. Neither gender, nationality nor city-wise significant differences were recorded. However, physically active PHCPs significantly impart advice and role modeling on physical activity to their patients compared to physically inactive PHCPs (p<0.01). CONCLUSION: Most PHCPs in Sakaka and Dumat Al-Jandal cities were physically active and were able to impart the healthy behavior counseling to their patients. A strong intention prevailed to increase physical activity among physically inactive Primary Health care Physicians (PHCPs). PMID- 26543421 TI - The Opinion of Students and Faculty Members about the Effect of the Faculty Performance Evaluation. AB - BACKGROUND: One of the most common ways that in most countries and Iran in determining the status of teacher training is the evaluation by students. The most common method of evaluation is the survey questionnaire provided to the study subjects, comprised of questions about educational activities. The researchers plan to evaluate the opinion of students and faculty members about the effect of the faculty performance evaluation at Mazandaran University of Medical Sciences in 2014-15. METHODS: In this descriptive cross-sectional survey of attitudes of students and professors base their evaluation on the impact on their academic performance, have been studied. The populations were 3904 students and 149 faculty members of basic sciences Mazandaran University of Medical Sciences. Sample of 350 students and 107 students using Cochran formula faculty members through proportional stratified random sampling was performed. The data of the questionnaire with 28 questions on a Likert Spectrum, respectively. Statistical Analysis Data are descriptive and inferential statistics using Kruskal-Wallis and Mann-Whitney U test is done. RESULTS: Based on the results obtained from total of 350 students, 309 students and from total of 107 faculty members, 76 faculty of basic sciences, participated in this study. The most of the students, 80 (25.9%) of the Faculty of Allied Medical Sciences and most of the faculty of basic sciences, 33 (4.43) of the medicine science faculty. Comments Mazandaran University of Medical Sciences in comparison to the scope of the evaluation should test using Binominal test; we can conclude that in the field of regulatory, scientific, educational, and communications arena, there were no significant differences between the views of students. The greatest supporter of the education of 193 (62%) and most challengers of exam 147 (48%), respectively. Regarding the viewpoints of the faculty members at Mazandaran University of Medical Sciences towards the evaluation domains, using binomial test, it could be concluded that only on the regulation domain with the significance level of 0.000, significant different was observed. So that, 30(23%) and 50(53%) supported of the effect of evaluation on the effect of evaluation of situation. Evaluation to improve the regulatory status of teachers and 70% (53 patients), the effects are positive. Students and faculty evaluations to compare the Mann-Whitney U test was used. The results show, only within the rules, with a significance level of 0.01 considered statistically significant relationship between teachers and students there. CONCLUSION: considering the viewpoints of students and faculty members about the impact of teacher performance evaluation of the students, most of the students believed that the greatest impact assessment has been on the improve educational performance entitled as responsibility of the faculty member for education, interest in presenting lessons, using audio-visual tools, having lesson plans, faculty members participate interest and enthusiasm in presenting lessons the use of teaching aids, lesson plans, faculty members participation in seminars, creating interest in students to participate in class discussions and expressing the importance of learning lessons perspective of teachers, but the faculty members viewpoints indicate the impact of evaluation on the regular attendance and discipline, the greatest impact assessment in the area of regulatory and compliance with the timely and orderly and thus their activities. PMID- 26543422 TI - Patient's Perception and Expectations of the Quality of Outpatient Services of Imam Khomeini Hospital in Sari City. AB - BACKGROUND AND PURPOSE: Out-patient department is the gateway to almost all of the hospital services. Providing method of service in this place has an important role in the general impression of the patient of hospital sanitary and treatment services. This research was done with the purpose of studying the perception and expectations of out-patient service receivers of Imam Khomeini Hospital in Sari. MATERIALS AND METHODOLOGY: A cross-sectional study was conducted on those patients in the outpatient service department of Imam Khomeini Hospital who at least have the junior high school degree. 200 people were selected as sample size with Morgan's table. Respondents answered the questionnaire two times. Once they expressed their perception of the provided services and once for their expectations. Therefore, the following expectation scores are obtained. To prove the significance of demographic variables with perception and expectations, the T and Tukey's tests and also to compare different groups the variance analysis test are used. FINDINGS: The mean of age was 25.68+/- 9.086 (The youngest participant was 16 and the oldest 67 years old). It was observed from the results of the T test there is no significant difference between sex and residential place. It was clear that in perception part; there was a significant difference, at the level of 0.05 significance, in all groups except for responding and behavior, while, in expectation level, no significance in the age of the dimensions except for access. CONCLUSION: Results showed that the satisfaction status of patients in Imam Hospital clinic in Sari is good. Many of the existing shortages can be improved by presenting an accurate and organized program. The present study shows that some service dimensions of patients require being promoted, the most important of which include behavior, accessibility and affordability, physical and responsiveness dimensions. PMID- 26543423 TI - Clinical Presentation and the Outcome of Therapy in a Cohort of Patients with Methadone Toxicity in Iran. AB - BACKGROUND: Agonist maintenance therapy with methadone is amongst the preferred remedies for treating opioid dependence and is increasingly supported by the regional governments in this part of the world. In this study we have investigated the clinical manifestations and factors affecting the outcome of therapy in patients with methadone poisoning in a Middle-Eastern (Iranian) referral tertiary care University hospital. METHODS: In this prospective and descriptive-analytic study which was done in a tertiary care and referral University hospital in Iran (2012-2013) all of the admitted patients with a clear and reliable history of methadone poisoning (n=433) were included and demographic data, Clinical status on admission including Glasgow Coma Scale (GCS) score, time elapsed from ingestion to hospital admission, average dose of naloxone used, any history of psychiatric disorder, type of toxic exposure, co ingestion of other medication, hospitalization time and the outcome were recorded and statistically analyzed. RESULTS: The average length of hospital stay was 33 +/- 26 hours. 80.1% of patients had ingested methadone alone, and 90.3% survived. Complications were pulmonary edema (7%), aspiration pneumonia (1.4%), generalized tonic colonic seizure (0.9%), and renal failure (0.5%). GCS, systolic blood pressure and respiratory rate were lower in fatal cases and GCS had prognostic value for the outcome of therapy in methadone intoxicated patients. Patients with higher GCS on admission had better outcome [OR =0.47 (95% CI: 0.38-0.580); P value< 0.0001]. CONCLUSION: Admission time GCS score maybe considered as an important predictor for the outcome of therapy in methadone poisoning. PMID- 26543424 TI - Social Capital Role in Managing High Risk Behavior: a Narrative Review. AB - BACKGROUND: Social capital as a social context based concept is a new component in addition to the previous factors including the biologic-environmental, the genetic and the individual behavior factors that influence health and society. Social capital refers to the information that makes people believe being interesting & being paid attention to, & respected, valued, and belonging to a network of bilateral relations. Health issue is greatly affected by the existence of social capital. High risk behaviors refer to the ones enhancing the probability of negative and devastating physical, psychological and social consequences for an individual. Negative & overwhelming results mean keeping one's distance from social norms as a result rejection and labeling (social stigma) and finally, to distance oneself from the benefits of social life in the individuals with high risk behaviors. The present study reviews social capital in the groups having high risk behaviors. METHODS: The present study is a narrative review in which researchers conducted their computer search in public databases like Google Scholar, and more specifically in Pubmed, Magiran, SID, Springer, Science Direct, and ProQuest using the keywords: social capital, social support, risk behaviors, addicts, HIV, AIDS, and selected the articles related to the study subject from 2004 to 2014. Overall 96 articles have been searched. Researchers reviewed the summary of all articles searched, & ultimately, they applied the data from 20 full articles to compile this review paper. RESULTS: Article review results led to organizing the subjects into 6 general categories: Social capital and its role in health; Social capital in groups with high risk behaviors (Including: substance abusers, AIDS patients, the homeless and multi partner women); Social capital in different social groups; measurement tools for social capital and risk behaviors; the role of health in helping people with risky behaviors with the focus on improving social capital and social support. The findings of this study indicate that social capital was significantly lower in the substance abusers than the non-addicts. Also, social participation, social trust and networks of social relationships were significantly lower than non-drug abusers. Social capital has interactive effects on risky behaviors and delinquency. On the one hand, high levels of social capital can be involved in preventing delinquency. On the other hand, creating negative social capital in high risk groups is also considered as the damaging effects of the negative aspects of social capital in these groups. CONCLUSIONS: From this review extracted findings, it can be concluded that to design risky behaviors programs and preventive interventions, social capital and social support should be considered more than before. To accept an addict or HIV sufferer is effective in reducing their psychological reactions. So with effective social interaction and social support, these people can improve their risky lifestyles. As a result, these changes are associated with higher levels of satisfaction with their lives. Finally, it is recommended to design and implement counseling programs in order to educate health-promoting behaviors in high risk groups focusing on social capital and social support. PMID- 26543425 TI - Couples Communication Skills and Anxiety of Pregnancy: A Narrative Review. AB - BACKGROUND: physical problems during pregnancy including Anxiety disorders form a large share of health problems. On the other hand, healthy relationship and communication skills are vital to raise a family. For couples who enjoy communication skills, parenthood will be the best and most pleasant experiences in their lives. High levels of positive communication will lead to couples and their children's mental health and couples' good relationship can have a protective effect against stressors including anxiety of pregnancy. The current study reviewed the studies on the relationship between communication skills and the anxiety of pregnancy. METHODS: The current study is a review where the researcher browsed the available databases like Google Scholar, Pubmed, Magiran, SID, and Science Direct and using key words of Communication skills, marital satisfaction, and the anxiety of pregnancy, & the researcher has searched the articles of 2000-2014 & read 150 abstracts & 93 full papers and ultimately, chose 50 to write this study. RESULTS: By reviewing the findings literature in three general categories as Communication Skills as the Significant Component to Get Marital Satisfaction, Improving Marital Satisfaction as Pregnancy Anxiety Reducing Factor, and Communication Skills Quality as Component Influencing Pregnancy Anxiety. CONCLUSIONS: Having communication skills will lead to promotion of marital satisfaction and increased mental health in life. It is, therefore, recommended that communication skills be trained in routine programs for pre-marriage counseling, pre-pregnancy cares and pregnancy so that the mental health of community can be improved. PMID- 26543426 TI - Metabolic Syndrome and Nephrolithiasis Risk: Should the Medical Management of Nephrolithiasis Include the Treatment of Metabolic Syndrome? AB - This article reviews the relationship between metabolic syndrome (MetS) and nephrolithiasis, as well as the clinical implications for patients with this dual diagnosis. MetS, estimated to affect 25% of adults in the United States, is associated with a fivefold increase in the risk of developing diabetes, a doubling of the risk of acquiring cardiovascular disease, and an increase in overall mortality. Defined as a syndrome, MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. Urologic complications of MetS include a 30% higher risk of nephrolithiasis, with an increased percentage of uric acid nephrolithiasis in the setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary volume. Current American Urological Association and European Association of Urology guidelines suggest investigating the etiology of nephrolithiasis in affected individuals; however, there is no specific goal of treating MetS as part of the medical management. Weight loss and exercise, the main lifestyle treatments of MetS, counter abdominal obesity and insulin resistance and reduce the incidence of cardiovascular events and the development of diabetes. These recommendations may offer a beneficial adjunctive treatment option for nephrolithiasis complicated by MetS. Although definitive therapeutic recommendations must await further studies, it seems both reasonable and justifiable for the urologist, as part of a multidisciplinary team, to recommend these important lifestyle changes to patients with both conditions. These recommendations should accompany the currently accepted management of nephrolithiasis. PMID- 26543427 TI - Conservative Management of Urinary Incontinence in Women. AB - Urinary incontinence in women has a high prevalence and causes significant morbidity. Given that urinary incontinence is not generally a progressive disease, conservative therapies play an integral part in the management of these patients. We conducted a nonsystematic review of the literature to identify high quality studies that evaluated the different components of conservative management of stress urinary incontinence, including behavioral therapy, bladder training, pelvic floor muscle training, lifestyle changes, mechanical devices, vaginal cones, and electrical stimulation. Urinary incontinence can have a severe impact on our healthcare system and patients' quality of life. There are currently a wide variety of treatment options for these patients, ranging from conservative treatment to surgical treatment. Although further research is required in the area of conservative therapies, nonsurgical treatments are effective and are preferred by some patients. PMID- 26543428 TI - The Role of Minimally Invasive Surgical Techniques in the Management of Large gland Benign Prostatic Hypertrophy. AB - Lower urinary tract symptoms (LUTS) secondary to benign prostatic hypertrophy (BPH) are among the most common medical issues for aging men. Population-based studies suggest that 13.8% of men in their 40s and more than 40% of men over age 60 have BPH. When LUTS are refractory to medical therapy and bothersome enough to warrant surgical intervention, transurethral resection of the prostate and open simple prostatectomy have been the historical reference-standard procedures for decades. Both procedures are highly effective and offer durable improvements in urinary functional outcomes. However, they also have the potential for considerable perioperative complications and morbidity. In an effort to limit surgical morbidity, a variety of minimally invasive surgical techniques to treat BPH have been introduced. Herein we present a comprehensive, evidence-based review of the efficacy and safety profile of modern minimally invasive treatments for large-gland BPH. PMID- 26543429 TI - Current Status of Hemostatic Agents and Sealants in Urologic Surgical Practice. AB - There has been a recent and near exponential increase in the use of hemostatic agents and sealants to supplement the rapidly evolving methods in the surgical management of urologic patients. This article reviews the use of hemostatic agents and sealants in current urologic practice. PMID- 26543430 TI - Optimizing Stone-free Rates With Ureteroscopy. AB - Ureteroscopy is being increasingly utilized in the treatment and management of patients with renal and ureteral stones. Improving stone-free rates with ureteroscopy decreases the need for ancillary procedures and improves patient outcomes and satisfaction. This article reviews contemporary literature regarding the efficacy of a wide range of currently available techniques for improving stone-free rates with this procedure. PMID- 26543431 TI - The Obesity Epidemic and Its Impact on Urologic Care. AB - Although heart disease and cancer are the number one and two causes of death in the United States, respectively, obesity is gaining speed as a contributing cause to both of those conditions, along with diabetes, arthritis, dyslipidemia, coronary heart disease, gallbladder disease, and certain malignancies. Nearly one third of the adults in the United States is overweight with a body mass index (BMI) greater than 25 kg/m(2), and another third of the adult population is obese, with a BMI greater than 30 kg/m(2). This article reviews the root causes of obesity, the societal implications, and the implications of obesity on various urologic diseases. PMID- 26543432 TI - Impact of the US Preventive Services Task Force Grade D Recommendation: Assessment of Evaluations for Elevated Prostate-specific Antigen and Prostate Biopsies in a Large Urology Group Practice Following Statement Revision. AB - On October 7, 2011, the United States Preventive Services Task Force (USPSTF) released their evidence statement and grade D recommendation against prostate specific antigen (PSA)-based prostate cancer screening. Using a time series design, we assessed the effect of this recommendation upon evaluations for elevated PSA levels and prostate biopsies in our large urology group practice. We found that, despite a 24.1% increase in total visits, the 32 urologists in our practice completed 16.4% fewer evaluations for elevated PSA levels (317 fewer evaluations per month; P = .017) and 21.4% fewer prostate biopsies (42 fewer biopsies per month; P = .001) in the 2 years following the USPSTF grade D recommendation. PMID- 26543433 TI - From the President's Desk: LUPGA Announces Its First CEO, Celeste Kirschner. PMID- 26543434 TI - Best of the 2015 AUA Annual Meeting: Highlights From the 2015 American Urological Association Annual Meeting, May 15-19, 2015, New Orleans, LA. PMID- 26543435 TI - Retroperitoneal Ancient Schwannoma: A Case Report. AB - Schwannomas are extremely rare tumors that are composed of Schwann cells. Retroperitoneal localization comprises 0.7% to 2.6% of all schwannomas. Patients usually present with nonspecific symptoms. There are no pathognomonic features on radiologic evaluation. Preoperative biopsy is not recommended because of complication risks; however, surgery is necessary for diagnosis and treatment. Although most schwannomas are benign tumors, those that are associated with von Recklinghausen disease are malignant. Schwannomas exhibit regions of high and low cellularity, termed Antoni A and Antoni B areas, with a diffuse positivity of S100 protein on pathologic evaluation. If there are degenerative changes, such as cyst formation, hemorrhage, calcification, and hyalinization, these tumors are termed ancient schwannomas. We present a case of retroperitoneal ancient schwannoma. PMID- 26543436 TI - Treatment of Colonic Injury During Percutaneous Nephrolithotomy. AB - Colonic injury during percutaneous nephrolithotomy (PCNL) persists despite the advances in technical equipment and interventional radiology techniques. According to the Clavien-Dindo classification of surgical complications, colonic injury is regarded as a stage IVa complication. Currently, the rate of colonic injury ranges between 0.3% and 0.5%, with an unremarkable difference in incidence between supine and prone PCNL procedures. Colon injury is the most significant complication of PCNL. Colonic injury can result in more complicated open exploration of the abdomen, involving colostomy construction. The necessity of a second operation for the closure of the colostomy causes financial and emotional burden on the patients, patients' relatives, and surgeons. Currently, the majority of colonic injuries occurring during PCNL are retroperitoneal. The primary treatment option is a conservative approach. It must be kept in mind that the time of diagnosis is as important as the diagnosis itself in colonic injury. Surgeons performing PCNL are advised to be conservative when considering exploratory laparotomy and colostomy construction during treatment of colonic injury. We present the case of a 49-year-old woman who underwent left prone PCNL that resulted in retroperitoneal colonic injury, along with a review of the current literature. PMID- 26543437 TI - Development of a Model Protein Interaction Pair as a Benchmarking Tool for the Quantitative Analysis of 2-Site Protein-Protein Interactions. AB - A significant challenge in the molecular interaction field is to accurately determine the stoichiometry and stepwise binding affinity constants for macromolecules having >1 binding site. The mission of the Molecular Interactions Research Group (MIRG) of the Association of Biomolecular Resource Facilities (ABRF) is to show how biophysical technologies are used to quantitatively characterize molecular interactions, and to educate the ABRF members and scientific community on the utility and limitations of core technologies [such as biosensor, microcalorimetry, or analytic ultracentrifugation (AUC)]. In the present work, the MIRG has developed a robust model protein interaction pair consisting of a bivalent variant of the Bacillus amyloliquefaciens extracellular RNase barnase and a variant of its natural monovalent intracellular inhibitor protein barstar. It is demonstrated that this system can serve as a benchmarking tool for the quantitative analysis of 2-site protein-protein interactions. The protein interaction pair enables determination of precise binding constants for the barstar protein binding to 2 distinct sites on the bivalent barnase binding partner (termed binase), where the 2 binding sites were engineered to possess affinities that differed by 2 orders of magnitude. Multiple MIRG laboratories characterized the interaction using isothermal titration calorimetry (ITC), AUC, and surface plasmon resonance (SPR) methods to evaluate the feasibility of the system as a benchmarking model. Although general agreement was seen for the binding constants measured using solution-based ITC and AUC approaches, weaker affinity was seen for surface-based method SPR, with protein immobilization likely affecting affinity. An analysis of the results from multiple MIRG laboratories suggests that the bivalent barnase-barstar system is a suitable model for benchmarking new approaches for the quantitative characterization of complex biomolecular interactions. PMID- 26543439 TI - An Efficient Method for Electroporation of Small Interfering RNAs into ENCODE Project Tier 1 GM12878 and K562 Cell Lines. AB - The Encyclopedia of DNA Elements (ENCODE) Project aims to identify all functional sequence elements in the human genome sequence by use of high-throughput DNA/cDNA sequencing approaches. To aid the standardization, comparison, and integration of data sets produced from different technologies and platforms, the ENCODE Consortium selected several standard human cell lines to be used by the ENCODE Projects. The Tier 1 ENCODE cell lines include GM12878, K562, and H1 human embryonic stem cell lines. GM12878 is a lymphoblastoid cell line, transformed with the Epstein-Barr virus, that was selected by the International HapMap Project for whole genome and transcriptome sequencing by use of the Illumina platform. K562 is an immortalized myelogenous leukemia cell line. The GM12878 cell line is attractive for the ENCODE Projects, as it offers potential synergy with the International HapMap Project. Despite the vast amount of sequencing data available on the GM12878 cell line through the ENCODE Project, including transcriptome, chromatin immunoprecipitation-sequencing for histone marks, and transcription factors, no small interfering siRNA-mediated knockdown studies have been performed in the GM12878 cell line, as cationic lipid-mediated transfection methods are inefficient for lymphoid cell lines. Here, we present an efficient and reproducible method for transfection of a variety of siRNAs into the GM12878 and K562 cell lines, which subsequently results in targeted protein depletion. PMID- 26543438 TI - Simultaneous Extraction of Viral and Bacterial Nucleic Acids for Molecular Diagnostic Applications. AB - Molecular detection of microbial pathogens in clinical samples requires the application of efficient sample lysis protocols and subsequent extraction and isolation of their nucleic acids. Here, we describe a simple and time-efficient method for simultaneous extraction of genomic DNA from gram-positive and negative bacteria, as well as RNA from viral agents present in a sample. This method compared well with existing bacterial- and viral-specialized extraction protocols, worked reliably on clinical samples, and was not pathogen specific. This method may be used to extract DNA and RNA concurrently from viral and bacterial pathogens present in a sample and effectively detect coinfections in routine clinical diagnostics. PMID- 26543441 TI - Mixed Ligand Complexes of N-Methyl-N-phenyl Dithiocarbamate: Synthesis, Characterisation, Antifungal Activity, and Solvent Extraction Studies of the Ligand. AB - A series of mixed ligand dithiocarbamate complexes with a general formula [ML2(py)2], where M = Mn(II), Co(II), Ni(II), and Cu(II), py = pyridine, and L = N-methyl-N-phenyl dithiocarbamate have been prepared and characterised by elemental analysis, FTIR and Uv spectroscopy, magnetic moment, and thermogravimetric and conductance analysis. The infrared spectra showed that symmetrical bidentate coordination occurred with the dithiocarbamate moiety through the sulfur atoms, while neutral monodentate coordination occurred through the nitrogen atom for the pyridine molecule in the complexes. The electronic spectra, elemental analysis, and magnetic moment results proved that the complexes adopted octahedral geometry. The conductance measurement showed that the complexes are nonelectrolytes proving their nonionic nature. The compounds were screened for three human pathogenic fungi: Aspergillus flavus, Aspergillus niger, and Candida albicans. The cobalt complex showed the best antifungal activity among the test compounds. Liquid-liquid extractive abilities of the ligand towards copper and nickel ions in different solvent media were investigated. The ligand showed a strong binding affinity towards the metals ions with an extractive efficiency of about 99%. PMID- 26543440 TI - Combining the Fluctuating Charge Method, Non-Periodic Boundary Conditions and Meta-Dynamics: Aqua Ions as case studies. AB - We present the current status of development of our code for performing Molecular Dynamics (MD) simulations exploiting a polarizable force field based on the Fluctuating Charge (FQ) method and non-Periodic Boundary Conditions (NPBC). Continuing on the path set in a previous work, we increased the capabilities of the code by implementing a number of new features, including: a non-iterative algorithm for rigid trigonal molecule simulations; two additional temperature coupling schemes; a meta-dynamics based approach for effective free energy evaluations. Although these are well known algorithms, each present in one or more widely used MD packages, they have now been tested, for the first time, in the context of the FQ model coupled with NPBC. As case studies, we considered three aqueous ions of increasing charge, namely Na+, Ca2+ and La3+, at infinite dilution. In particular, by exploiting a computational approach recently proposed by our group and based on the metadynamics technique, we focused on the important role played by solvent polarization on ionic hydration structures, also investigating the free energy landscapes of ion coordination and the water exchange rates. Such an approach, previously tested with standard non-polarizable models, was applied here to evaluate the effects of explicit polarization on water exchange barriers between different solvent coordination structures. Moreover, we have analyzed and discussed in some detail non-linear electrostatic effects arising from solvent polarization while going from a mono- to a di- and trivalent ion. PMID- 26543442 TI - Optimizing pentacene thin-film transistor performance: Temperature and surface condition induced layer growth modification. AB - In this work we present in situ electrical and surface analytical, as well as ex situ atomic force microscopy (AFM) studies on temperature and surface condition induced pentacene layer growth modifications, leading to the selection of optimized deposition conditions and entailing performance improvements. We prepared p++-silicon/silicon dioxide bottom-gate, gold bottom-contact transistor samples and evaluated the pentacene layer growth for three different surface conditions (sputtered, sputtered + carbon and unsputtered + carbon) at sample temperatures during deposition of 200 K, 300 K and 350 K. The AFM investigations focused on the gold contacts, the silicon dioxide channel region and the highly critical transition area. Evaluations of coverage dependent saturation mobilities, threshold voltages and corresponding AFM analysis were able to confirm that the first 3-4 full monolayers contribute to the majority of charge transport within the channel region. At high temperatures and on sputtered surfaces uniform layer formation in the contact-channel transition area is limited by dewetting, leading to the formation of trenches and the partial development of double layer islands within the channel region instead of full wetting layers. By combining the advantages of an initial high temperature deposition (well-ordered islands in the channel) and a subsequent low temperature deposition (continuous film formation for low contact resistance) we were able to prepare very thin (8 ML) pentacene transistors of comparably high mobility. PMID- 26543443 TI - Production of hyperpolarized 13CO2 from [1-13C]pyruvate in perfused liver does reflect total anaplerosis but is not a reliable biomarker of glucose production. AB - In liver, 13CO2 can be generated from [1-13C] pyruvate via pyruvate dehydrogenase or anaplerotic entry of pyruvate into the TCA cycle followed by decarboxylation at phosphoenolpyruvate carboxykinase (PEPCK), the malic enzyme, isocitrate dehydrogenase, or alpha-ketoglutarate dehydrogenase. The purpose of this study was to determine the relative importance of these pathways in production of hyperpolarized (HP) 13CO2 after administration of hyper-polarized pyruvate in livers supplied with a fatty acid plus substrates for gluconeogenesis. Isolated mouse livers were perfused with a mixture of thermally-polarized 13C-enriched pyruvate, lactate and octanoate in various combinations prior to exposure to HP pyruvate. Under all perfusion conditions, HP malate, aspartate and fumarate were detected within ~ 3 s showing that HP [1-13C]pyruvate is rapidly converted to [1 13C]oxaloacetate which can subsequently produce HP 13CO2 via decarboxylation at PEPCK. Measurements using HP [2-13C]pyruvate allowed the exclusion of reactions related to TCA cycle turnover as sources of HP 13CO2. Direct measures of O2 consumption, ketone production, and glucose production by the intact liver combined with 13C isotopomer analyses of tissue extracts yielded a comprehensive profile of metabolic flux in perfused liver. Together, these data show that, even though the majority of HP 13CO2 derived from HP [1-13C]pyruvate in livers exposed to fatty acids reflects decarboxylation of [4-13C]oxaloacetate (PEPCK) or [4 13C]malate (malic enzyme), the intensity of the HP 13CO2 signal is not proportional to glucose production because the amount of pyruvate returned to the TCA cycle via PEPCK and pyruvate kinase is variable, depending upon available substrates. PMID- 26543444 TI - A Synergistic Combinatorial and Chiroptical Study of Peptide Catalysts for Asymmetric Baeyer-Villiger Oxidation. AB - We report an approach to the asymmetric Baeyer-Villiger oxidation utilizing bioinformatics-inspired combinatorial screening for catalyst discovery. Scaled-up validation of our on-bead efforts with a circular dichroism-based assay of alcohols derived from the products of solution-phase reactions established the absolute configuration of lactone products; this assay proved equivalent to HPLC in its ability to evaluate catalyst performance, but was far superior in its speed of analysis. Further solution-phase screening of a focused library suggested a mode of asymmetric induction that draws distinct parallels with the mechanism of Baeyer-Villiger monooxygenases. PMID- 26543445 TI - Comments on "combination of dexmedetomidine and remifentanil for labor analgesia: A double-blinded, randomized, controlled study". PMID- 26543446 TI - Hemodynamic response to endotracheal intubation using C-Trach assembly and direct laryngoscopy. AB - PURPOSE: Our objective was to study the pressor response to endotracheal intubation through laryngeal mask airway C-Trach and compare it to the hemodynamic response to intubation with direct laryngoscopy (DL). MATERIALS AND METHODS: After obtained approval from institutional ethical committee, 100 patients of American Society of Anesthesiologists physical Status I, aged 14-65 years, posted for elective surgery were enrolled in the trial. They were randomly divided into two groups of each 50 patients. Anesthesia technique was standardized and patients of Group I were intubated using DL, while patients of Group II were intubated with the help of C-Trach assembly. Hemodynamic parameters, systemic blood pressure (systolic and diastolic) and heart rate were recorded before and after induction of anesthesia and every minute up to 5 min after intubation. RESULTS: Patients of Group II recorded a minimal rise in peak systolic blood pressure (SBP) (1.8%) and diastolic blood pressure (10.6%). In comparison patients of Group I recorded a significant sustained rise in peak SBP (20.3%) and diastolic blood pressure (21.4%). However heart rate changes recorded in the two groups were of equal measure (peak rise of 22.9% in Group I vs. 22.4% in Group II). CONCLUSION: We conclude that intubation through C-Trach generates a lower pressor response to intubation in comparison to intubation using DL. PMID- 26543447 TI - Success rates and complications of awake caudal versus spinal block in preterm infants undergoing inguinal hernia repair: A prospective study. AB - BACKGROUND: Inguinal hernia is a common disease in preterm infants necessitating surgical repair. Despite the increased risk of postoperative apnea in preterm infants, the procedure was conventionally performed under general anesthesia. Recently, regional anesthesia approaches, including spinal and caudal blocks have been proposed as safe and efficient alternative anesthesia methods in this group of patients. The current study evaluates awake caudal and spinal blocks in preterm infants undergoing inguinal hernia repair. MATERIALS AND METHODS: In a randomized clinical trial, 66 neonates and infants (weight <5 kg) undergoing inguinal hernia repair were recruited in Tabriz Teaching Children Hospital during a 12-month period. They were randomly divided into two equal groups; receiving either caudal block by 1 ml/kg of 0.25% bupivacaine plus 20 MUg adrenaline (group C) or spinal block by 1 mg/kg of 0.5% bupivacaine plus 20 MUg adrenaline (group S). Vital signs and pain scores were documented during operation and thereafter up to 24 h after operation. RESULTS: Decrease in heart rate and systolic blood pressure was significantly higher in group C throughout the study period (P < 0.05). The mean recovery time was significantly higher in group S (27.3 +/- 5.5 min vs. 21.8 +/- 9.3 min; P = 0.03). Postoperative need for analgesia was significantly more frequent in group S (75.8% vs. 36.4%; P = 0.001). Failure in anesthesia was significantly higher in group S (24.4% vs. 6.1%; P = 0.04). CONCLUSION: More appropriate success rate, duration of recovery and postoperative need of analgesics could contribute to caudal block being a superior anesthesia technique compared to spinal anesthesia in awaked preterm infants undergoing inguinal hernia repair. PMID- 26543448 TI - Dexmedetomidine as an adjunct in postoperative analgesia following cardiac surgery: A randomized, double-blind study. AB - OBJECTIVES: The purpose of this study was to determine analgesic efficacy of dexmedetomidine used as a continuous infusion without loading dose in postcardiac surgery patients. SETTINGS AND DESIGN: A prospective, randomized, double-blind clinical study in a single tertiary care hospital on patients posted for elective cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: Sixty-four patients who underwent elective cardiac surgery under general anesthesia were shifted to intensive care unit (ICU) and randomly divided into two groups. Group A (n = 32) received a 12 h infusion of normal saline and group B (n = 32) received a 12 h infusion of dexmedetomidine 0.4 MUg/kg/h. Postoperative pain was managed with bolus intravenous fentanyl. Total fentanyl consumption, hemodynamic monitoring, Visual Analogue Scale (VAS) pain ratings, Ramsay Sedation Scale were charted every 6(th) hourly for 24 h postoperatively and followed-up till recovery from ICU. Student's t-test, Chi-square/Fisher's exact test has been used to find the significance of study parameters between the groups. RESULTS: Dexmedetomidine treated patients had significantly less VAS score at each level (P < 0.001). Total fentanyl consumption in dexmedetomidine group was 128.13 +/- 35.78 MUg versus 201.56 +/- 36.99 MUg in saline group (P < 0.001). A statistically significant but clinically unimportant sedation was noted at 6 and 12 h (P < 0.001, and P = 0.046 respectively). Incidence of delirium was less in dexmedetomidine group (P = 0.086+). Hemodynamic parameters were statistically insignificant. CONCLUSIONS: Dexmedetomidine infusion even without loading dose provides safe, effective adjunct analgesia, reduces narcotic consumption, and showed a reduced trend of delirium incidence without undesirable hemodynamic effects in the cardiac surgery patients. PMID- 26543449 TI - Stress response in shoulder surgery under interscalene block, randomized controlled study comparing ultrasound guidance to nerve stimulation. AB - BACKGROUND: Shoulder surgeries are known to cause moderate to severe pain. Many techniques have been used successfully to minimize that stress response including interscalene block. Ultrasound guided techniques are becoming widely spread and commonly used for regional anesthesia. The objective of the present randomized controlled study is to compare the ultrasound guidance with nerve stimulation for interscalene brachial plexus block (IBPB) regarding the effect on stress response. PATIENTS AND METHODS: 50 patients, American Society of Anesthesiologists physical status I, II, and III, undergoing shoulder surgery were enrolled in the current study. Group U patients (n = 25) received ultrasound guided IBPB and Group N patients (n = 25) received IBPB using nerve locator. IBPB was done under ultrasound guidance using the linear 13-6 MHz transducer of the SonoSite M-Turbo ultrasonic device. In both groups, venous blood samples to measure cortisol level and assess stress response as a primary outcome were collected. RESULTS: The current study demonstrated that the stress response, as indicated by the cortisol level in blood, showed no significant difference in the preoperative blood level between Group U and Group N, as well as blood level after block and before skin incision. However, it differed significantly between the two groups postoperatively. CONCLUSION: The current study concluded that the use of ultrasound guidance for IBPB in shoulder surgeries offered a significant suppression of the stress response intraoperatively and postoperatively as indicated by the low cortisol level with less complications and easier technique compared to nerve location. PMID- 26543450 TI - Effect of ondansetron on prevention of post-induction hypotension in elderly patients undergoing general anesthesia: A randomized, double-blind placebo controlled clinical trial. AB - BACKGROUND: Elderly patients are susceptible to post-induction hypotension. Volume loading and vasopressors for prevention of hypotension in elderly patients may increase perioperative cardiovascular risks. Ondansetron by blocking Bezold Jarisch reflex (BJR) through inhibition of serotonin receptors has been effective in the prevention of post-spinal hypotension, and bradycardia. Bradycardia frequently accompanies post-induction hypotension in elderly patients, which signifies a possible preventing role for ondansetron. No previous study has evaluated the prophylactic effects of ondansetron for the prevention of post induction hypotension. MATERIALS AND METHODS: In this randomized placebo controlled clinical trial, ondansetron 4 mg was given intravenously to 65 elderly patients, 20 min before induction of general anesthesia, and the rate of post induction hypotension defined as 25% or more reduction in mean arterial blood pressure, compared with a placebo groups. RESULTS: A total of 114 patients completed the study (58 in ondansetron and 56 in the placebo group). Proportions of post-induction hypotension were 9 (16%) and 25 (45%) in ondansetron and placebo groups, respectively, (P = 0.001). Forty-five patients (40%) developed bradycardia. Rates of bradycardia were not significantly different between two groups. CONCLUSIONS: The results of this study show the effectiveness of intravenous ondansetron for prevention of post-induction hypotension in elderly patients. The mechanism of this effect largely is unknown. Role of ondansetron for prevention of post-induction hypotension may not fully understandable by its interaction with BJR, as has been shown in post-spinal hypotension. PMID- 26543451 TI - Efficacy of the methoxyflurane as bridging analgesia during epidural placement in laboring parturient. AB - BACKGROUND: Establishing an epidural in an agitated laboring woman can be challenging. The ideal pain control technique in such a situation should be effective, fast acting, and short lived. We assessed the efficacy of inhalational methoxyflurane (PenthroxTM) analgesia as bridging analgesia for epidural placement. MATERIALS AND METHODS: Sixty-four laboring women who requested epidural analgesia with pain score of >=7 enrolled in an observational study, 56 of which completed the study. The parturients were instructed to use the device prior to the onset of uterine contraction pain and to stop at the peak of uterine contraction, repeatedly until epidural has been successfully placed. After each (methoxyflurane inhalation-uterine contraction) cycle, pain, Richmond Agitation Sedation Scale (RASS), nausea and vomiting were evaluated. Maternal and fetal hemodynamics and parturient satisfaction were recorded. RESULTS: The mean baseline pain score was 8.2 +/- 1.5 which was reduced to 6.2 +/- 2.0 after the first inhalation with a mean difference of 2.0 +/- 1.1 (95% confidence interval 1.7-2.3, P < 0.0001), and continued to decrease significantly over the study period (P < 0.0001). The RASS scores continuously improved after each cycle (P < 0.0001). Only 1 parturient from the cohort became lightly sedated (RASS = -1). Two parturients vomited, and no significant changes in maternal hemodynamics or fetal heart rate changes were identified during treatment. 67% of the parturients reported very good or excellent satisfaction with treatment. CONCLUSION: PenthroxTM provides rapid, robust, and satisfactory therapy to control pain and restlessness during epidural placement in laboring parturient. PMID- 26543453 TI - ED50 of sevoflurane for I-Gel removal in anesthetized children in cataract surgeries using subtenon block. AB - OBJECTIVE: The aim of this study was to determine the minimum concentration of sevoflurane required for I-Gel removal in 50% children undergoing elective cataract surgery. DESIGN: A prospective observational study. SETTING: A single tertiary care surgical center. MATERIALS AND METHODS: Our study enrolled 20 American Society of Anesthesiologists I and II children aged 2-10 years, undergoing elective cataract surgery. Anesthesia was induced with sevoflurane and oxygen/nitrous oxide mixture and a size 2 I-Gel was inserted. A subtenon block was administered in all children before surgical incision. Sevoflurane was used for maintenance of anesthesia. Predetermined end-tidal concentration of sevoflurane was maintained for 10 min at the end of surgery before I-Gel removal was attempted. End-tidal concentrations were increased/decreased using the Dixon up-down method (with 0.2% as a step size) in the next patient depending on the previous patient's response. Patient responses to I-Gel removal were classified as "movement" or no "movement". RESULTS: Minimum concentration of sevoflurane required for successful removal of a I-Gel in 50% (ED50) and 95% (ED95) of children was 0.44% (95% confidence interval [CI], 0.34-0.52%) and 0.77% (95% CI, 0.63-1.2%), respectively. CONCLUSION: A very low end-tidal concentration of sevoflurane (ED50 of 0.44% ED95 of 0.77%) is required for I-Gel removal in children in cataract surgery with the supplementation of subtenon block. PMID- 26543452 TI - Comparative study between paracetamol and two different doses of pregabalin on postoperative pain in laparoscopic cholecystectomy. AB - BACKGROUND: Postoperative pain is the primary reason for prolonged hospital stay after laparoscopic cholecystectomy. This study compared the effect of a single oral preoperative administration of paracetamol (1 g) with 2 different doses of pregabalin (150 or 300 mg) for attenuating postoperative pain and analgesic consumption. MATERIALS AND METHODS: Seventy-five patients, aged 18-60 years, American Society of Anesthesiologists' physical status I and II undergoing elective laparoscopic cholecystectomy were included in this randomized controlled study. Patients were divided into three groups, 25 each to receive either oral paracetamol 1 g (group I, control group) or pregabalin 150 (group II) or 300 mg (group III), 2 h before surgery. Postoperative pain was evaluated based on visual analog scale over a period of 6 h and 1(st) time for rescue analgesia. Postoperative sedation, hemodynamic changes, serum cortisol level, and side effects were also evaluated. RESULTS: There was a significant decrease in mean heart rate, mean systolic blood pressure, sedation score, pain score, and delayed the first request for analgesics postoperatively in group (II) and group (III) compared to group (I) 2 h postoperatively. There was no significant difference in group (III) compared to group (II) postoperatively. The incidence of postoperative side effects was more in group (III). CONCLUSION: The single oral preoperative dose administration of pregabalin had significant opioid-sparing effect in the first 6 h after surgery, whereas side effects were more common with administration of pregabalin 300 mg. PMID- 26543454 TI - The effects of dexmedetomidine on attenuation of hemodynamic changes and there effects as adjuvant in anesthesia during laparoscopic surgeries. AB - BACKGROUND: As an anesthetic adjuvant dexmedetomidine has been shown to provide good perioperative hemodynamic stability with minimum alveolar concentration sparing effect on inhalational anesthetic agents during laparoscopic surgeries performed under general anesthesia. AIM: The study was planned to investigate the effects of dexmedetomidine on attenuation of hemodynamic changes and requirements of intra-operative analgesic and inhalational anesthetic during laparoscopic surgeries and its postoperative side effects. MATERIALS AND METHODS: A total of 70 patients scheduled for elective laparoscopic surgeries were randomized to receive bolus infusion of dexmedetomidine (group D) or saline (group S) 1 mcg/kg/h, followed by continuous infusion of the same, at the rate of 0.5 mcg/kg/h. Anesthesia was maintained with nitrous oxide in oxygen, muscle relaxant and isoflurane. Supplementation with end-tidal isoflurane was considered when heart rate (HR) and mean arterial blood pressure (BP) exceeded 20% of the baseline value. Hemodynamics, end-tidal isoflurane concentration and adverse events were recorded. RESULTS: Intra-operative mean HR and mean BP in group D were lower than group S (P < 0.05) throughout the laparoscopy surgery. Requirement of intra-operative fentanyl, end-tidal isoflurane and postoperative tramadol were significantly more in group S compared to group D (P < 0.05) Statistically significant nausea and vomiting were noted in group S. Undue sedation and other adverse effects are comparable in both the groups. CONCLUSION: Dexmedetomidine as an adjuvant in general anesthesia for laparoscopic surgeries provided a stable hemodynamic profile in the perioperative period and effectively blunted pressor response to intubation and extubation, leading to minimal requirements for additional analgesics and potent inhalational agents. There were less adverse events. PMID- 26543455 TI - Midazolam as an adjuvant to intrathecal lignocaine: A prospective randomized control study. AB - CONTEXT: Unfortunately in the past decade, phenomenon of transient neurologic symptoms (TNS) cast doubts on the use of lignocaine for spinal anesthesia. Intrathecal midazolam has been proved to have its role in relieving neuropathic pain. We attempted to study the role of midazolam as an adjuvant to intrathecal lignocaine. AIMS: The primary objective of the study was to evaluate the effect of intrathecal midazolam as an adjuvant to spinal lignocaine in terms of quality and duration of spinal sensory blockade. The secondary objectives are to study the effect on hemodynamics and the incidence of TNS. SETTINGS AND DESIGN: A prospective randomized control double-blinded study in American Society of Anesthesiology I and II surgical population. MATERIALS AND METHODS: Hundred healthy adult patients scheduled for elective infraumbilical surgery were randomly assigned to group A patients received spinal anesthesia with 1.5 ml of 5% lignocaine heavy with 0.4 ml of 0.9% saline and group B (control group) received spinal anesthesia with 1.5 ml of 5% heavy lignocaine with 0.4 ml of preservative-free 0.5% midazolam. STATISTICAL ANALYSIS USED: Z test for study parameters and analysis of variance was used for hemodynamic parameters in the same group. P < 0.05 was considered statistically significant. RESULTS: Midazolam resulted in improved quality of sensory blockade in terms of early onset, increased duration of effective analgesia, and delayed two segment regression time and also decreases the incidence of TNS with intrathecal lignocaine. CONCLUSIONS: Midazolam is an effective adjuvant to intrathecal lignocaine. PMID- 26543456 TI - Articaine and mepivacaine buccal infiltration in securing mandibular first molar pulp anesthesia following mepivacaine inferior alveolar nerve block: A randomized, double-blind crossover study. AB - AIMS: A crossover double-blind, randomized study was designed to explore the efficacy of 2% mepivacaine with 1:100,000 adrenaline buccal infiltration and 4% articaine with 1:100,000 adrenaline buccal infiltration following 2% mepivacaine with 1:100,000 adrenaline inferior alveolar nerve block (IANB) for testing pulp anesthesia of mandibular first molar teeth in adult volunteers. MATERIALS AND METHODS: A total of 23 healthy adult volunteers received two regimens with at least 1-week apart; one with 4% articaine buccal infiltration and 2% mepivacaine IANB (articaine regimen) and another with 2% mepivacaine buccal infiltration supplemented to 2% mepivacaine IANB (mepivacaine regimen). Pulp testing of first molar tooth was electronically measured twice at baseline, then at intervals of 2 min for the first 10 min, then every 5 min until 45 min postinjection. Anesthetic success was considered when two consecutive maximal stimulation on pulp testing readings without sensation were obtained within 10 min and continuously sustained for 45 min postinjection. RESULTS: In total, the number of no sensations to maximum pulp testing for first molar teeth were significantly higher after articaine regimen than mepivacaine during 45 min postinjection (267 vs. 250 episodes, respectively, P < 0.001), however, both articaine and mepivacaine buccal infiltrations are equally effective in securing anesthetic success for first molar pulp anesthesia when supplemented to mepivacaine IANB injections (P > 0.05). Interestingly, volunteers in the articaine regimen provided faster onset and longer duration (means 2.78 min, 42.22 min, respectively) than mepivacaine regimen (means 4.26 min, 40.74 min, respectively) for first molar pulp anesthesia (P < 0.001). CONCLUSIONS: Supplementary mepivacaine and articaine buccal infiltrations produced similar successful first molar pulp anesthesia following mepivacaine IANB injections in volunteers. Articaine buccal infiltration produced faster onset and longer duration than mepivacaine buccal infiltration following mepivacaine IANB injections. PMID- 26543457 TI - Comparison of dexmedetomidine and clonidine as an adjuvant to ropivacaine for epidural anesthesia in lower abdominal and lower limb surgeries. AB - BACKGROUND: The quality and duration of analgesia is improved when a local anesthetic is combined with alpha 2 adrenergic agonist. Though, the effects of clonidine on local anesthetics have been extensively studied, there are limited studies demonstrating the effects of epidural dexmedetomidine on local anesthetics. The aim of our study is to compare the effect of clonidine and dexmedetomidine when used as an adjuvant to epidural ropivacaine in lower abdominal and lower limb surgeries. MATERIALS AND METHODS: Patients were randomized into two groups-group ropivacaine with clonidine (RC) received 15 ml of 0.75% ropivacaine with 1 MUg/kg clonidine and group ropivacaine with dexmedetomidine (RD) received 15 ml of 0.75% ropivacaine with 1 MUg/kg dexmedetomidine epidurally. Onset of sensory analgesia using cold swab, onset of motor blockade using Bromage scale, time to 2 dermatome regression of sensory level, time to first demand for analgesia, sedation using Ramsay sedation scale, intra operative hemodynamic parameters and complications were assessed. RESULTS: The onset (RD-8.53 +/- 1.81, RC-11.93 +/- 1.96) and duration of sensory blockade (RD-316 +/- 31.5, RC-281 +/- 37, sedation were found to be significantly better in the dexmedetomidine group. No significant difference was found in terms of onset of motor blockade and hemodynamic changes. CONCLUSION: Dexmedetomidine at doses of 1 MUg/kg is an effective adjuvant to ropivacaine for epidural anesthesia, which is comparable to clonidine. PMID- 26543458 TI - Endotracheal intubation without muscle relaxants in children using remifentanil and propofol: Comparative study. AB - INTRODUCTION: Endotracheal intubation is essential during general anesthesia and muscle relaxant drugs provide ideal conditions for this purpose. The objective of this study was to evaluate the intubating condition of remifentanil combined with propofol without muscle relaxant. MATERIALS AND METHODS: In this prospective randomized study, 60 children aged 3-12 years, American Society of Anesthesiologists physical status I and II were included. All the children were premedicated with 0.05 mg/kg midazolam and 1.5 mg/kg lidocaine 5 min before the induction of anesthesia with 3 mg/kg propofol. Then, they were allocated randomly to receive either 2 MUg/kg remifentanil (group R) or 1.5 mg/kg succinylcholine (group S). Tracheal intubation was attempted 90 s after the administration of propofol. The quality of intubation was assessed by using Copenhagen score based on jaw relaxation, ease of laryngoscopy, position of vocal cord, coughing and limb movement. Heart rate and blood pressure were recorded before and after induction, and 1, 3, 5 min after intubation. RESULTS: There was no significant difference in intubating condition between the two groups (P = 0.11). Intubation condition was excellent in 26 of 30 (86.7%) patients in the group R compared with 30 (100%) patients in the group S. We observed significant difference in heart rate and systolic blood pressure over time between two groups (P = 0.02, P = 0.03 respectively). After intubation, we had higher heart rate and systolic blood pressure with a significant difference in group S compared with group R (P = 0.006, P = 0.018). None of the children had a chest rigidity, laryngospasm, and hypoxia. CONCLUSIONS: In premedicated children, propofol-remifentanil combination provides adequate conditions for tracheal intubation that is comparable with succinylcholine. Hemodynamic response to laryngoscopy and tracheal intubation was controlled better in group R. PMID- 26543459 TI - Comparative study of preoperative use of oral gabapentin, intravenous dexamethasone and their combination in gynaecological procedure. AB - BACKGROUND: We studied the effects of oral gabapentin and intravenous (I.V.) dexamethasone given together or separately 1 h before the start of surgery on intraoperative hemodynamics Postoperative analgesia and postoperative nausea vomiting (PONV) in patients undergoing gynaecological procedure. MATERIALS AND METHODS: Patients were randomly divided into three groups: Group 1 (gabapentin, n = 46) received 400 mg gabapentin, Group 2 (dexamethasone, n = 46) received 8 mg dexamethasone and Group 3 (gabapentin plus dexamethasone, n = 46) received both 400 mg gabapentin and 8 mg dexamethasone I.V. 1 h before the start of surgery. Standard induction and maintenance of anesthesia were accomplished. Visual analog scale for pain was recorded for 12 h. Side effects were noted. RESULTS: Hemodynamics at various time interval (0, 5, 10, 15, 20, 25 and 30 min) of laryngeal mask airway insertion and PONV were found significantly lower in Group 3 than in Group 1 and Group 2 (P < 0.05). The average time to first postoperative analgesic requirement at (visual analogue score >3) was significantly longer in Group 3 (510.00 +/- 61.64 min) than in Group 1 (352.83 +/- 80.61 min) and in Group 2 (294.78 +/- 60.76 min), (P < 0.05). CONCLUSION: The present study concludes that the combination of oral Gabapentin and I.V. dexamethasone has significantly less hemodynamic changes, better postoperative analgesia and less incidence of PONV than individual administration of each drug. PMID- 26543460 TI - Evaluating the quality of intravenous regional anesthesia following adding dexamethasone to lidocaine. AB - OBJECTIVES: The quality of anesthesia in intravenous regional anesthesia (IVRA) has been evaluated in many studies so far. This study was designed to evaluate the effects of adding the dexamethasone to lidocaine on the quality of IVRA. MATERIALS AND METHODS: A double-blind clinical trial was set up involving 50 hand surgery candidates, 20 to 55 years old, and with American Society of Anesthesiologists class of I and II. Patients were randomly allocated into two groups of 25 cases and received either 3 mg/kg of lidocaine (control group) or 3 mg/kg of lidocaine plus 8 mg of dexamethasone (study group). The onset and recovery times from sensory and motor blocks, the starting time of tourniquet pain, the amount of narcotics needed during patients' recovery, and probable side effects were all compared between the two groups. RESULTS: No significant differences were detected concerning age, gender, length of surgery and the mean time of starting of tourniquet pain between the two groups. The mean times of both sensory (P = 0.002) and motor (P = 0.004) blocks onset were significantly shorter in the study group. The mean time of recovery from sensory block was significantly longer in the study group (P = 0.01). The average amount of narcotics needed during the recovery was significantly lower in the study group (P = 0.01). No side-effect was detected. CONCLUSION: We conclude that adding the dexamethasone to lidocaine can improve the quality of anesthesia in IVRA. PMID- 26543461 TI - Effect of preinduction low-dose ketamine bolus on intra operative and immediate postoperative analgesia requirement in day care surgery: A randomized controlled trial. AB - BACKGROUND: Availability of narcotics is an issue in developing countries, and low-dose ketamine offers an alternative to these drugs. OBJECTIVE: The objective of this study is to evaluate the effect of a preemptive dose of low-dose ketamine on intra operative and the immediate postoperative analgesic requirements. DESIGN: Randomized double-blind control trial. SETTINGS: This study has been performed in the operating rooms and postanesthesia care unit at Aga Khan University Hospital, Karachi, Pakistan. MATERIALS AND METHODS: Totally, 60 adult American Society of Anesthesiologists I and II patients undergoing day care surgery were randomly allocated into two groups, Group A (ketamine group) and Group B (saline group). INTERVENTION: All patients underwent general anesthesia. Propofol 2 mg/kg was used as an induction agent; laryngeal mask airway (size 3 for females and 4 for males) was inserted. Following induction patients in Group A received ketamine 0.3 mg/kg and Group B saline bolus in a blinded manner. All patients were administered injection fentanyl 1 MUg/kg as an analgesic and anesthesia was maintained with oxygen 40%, nitrous oxide 60% and isoflorane 1-2 minimum alveolar concentration. Patients breathed spontaneously on Lack circuit. Postoperatively rescue analgesia was provided with intravenous morphine 0.1 mg/kg when patient complained of pain. MAIN OUTCOME MEASURES: We observed analgesic effects of low-dose ketamine intra operatively and narcotic requirements in immediate postoperative period for day care surgeries. RESULTS: There was no significant difference in demographic data in between groups. Saline group required more rescue analgesia (morphine) postoperatively (P < 0.001). No significant psychotomimetic symptoms were noted in either group. CONCLUSION: Low dose ketamine 0.3 mg/kg provided adequate co-analgesia with fentanyl 1 MUg/kg and was effective in a reduction of morphine requirement in the postoperative phase with minimal adverse effects. PMID- 26543462 TI - The rapid response team in outpatient settings identifies patients who need immediate intensive care unit admission: A call for policy maker. AB - BACKGROUND: Caregivers in the ambulatory care setting with differing clinical background could encounter a patient at high risk of deterioration. In the absence of a dedicated acute care team, the response to an unanticipated medical emergencies in these settings is likely to have a poor outcome. OBJECTIVE: To describe our experience in implementing an intensivist-led rapid response team (RRT) in the outpatient settings that identified patients who needed immediate Intensive Care Unit (ICU) admission. The effect on in hospital arrests, mortality, and ICU outcome is not the scope of this study. MATERIALS AND METHODS: This retrospective descriptive study was performed from January 1, 2009 to December 31, 2011 in a tertiary hospital. Data from hospital records were used (none from patients' records). Consent was not needed. MEASUREMENTS: Direct ICU admissions from the outpatient areas. RESULTS: There were 90 patients cared for by RRT in the outpatient's settings, 76 adult, and 14 pediatric patients. A total of12 adult patients were transferred directly to ICU. Among the patient who were transferred to the emergency department, additional four patients required to be transferred to ICU (total 16 patients [17.7%], 15 adult, and one pediatric patient). Follow-up at 24 h in the ICU showed death of one adult oncology patient (6.25%), and discharge of two patients (12.5%). Nine patients (81%) were still sick to require longer ICU stay. CONCLUSION: Intensivist-led RRT in outpatient settings identifies patients who are critically ill and in need of immediate ICU admission. Thus, an intensivist-led RRT policy in the outpatient settings needs to be implemented hospital wide. PMID- 26543463 TI - Combination of dexmedetomidine and remifentanil for labor analgesia: A double blinded, randomized, controlled study. AB - BACKGROUND: Satisfactory analgesia is of great importance in the labor. The clinical efficacy and side effects of remifentanil in the management of labor pain had been evaluated. Dexmedetomidine (DMET) demonstrates an antinociceptive effect in visceral pain conditions. Aims of the study were to assess whether the combination of DMET with remifentanil would produce a synergistic effect that results in lower analgesic requirements. Furthermore, whether this combination would have less maternal and neonatal adverse effects. PATIENTS AND METHODS: Sixty American Society of Anesthesiologists physical status I-II pregnant women had been enrolled into this study. All were full term (37-40 weeks' gestation), singleton fetus with cephalic presentation in the first stage of spontaneous labor. They were divided into two groups group (I) Patient-controlled IV remifentanil analgesia (bolus dose 0.25 MUg/kg, lockout interval 2 min) increased by 0.25 MUg/kg to a maximum bolus dose 1 MUg/kg in addition to a loading dose of DMET 1 MUg/kg over 20 min, followed by infusion at 0.5 MUg/kg/h group (II) Patient-controlled IV remifentanil analgesia (PCA) (bolus dose 0.25 MUg/kg, lockout interval 2 min) increased by 0.25 MUg/kg to a maximum bolus dose 1 MUg/kg in addition to a the same volume of normal saline as a loading dose, followed by a continuous saline infusion. Visual analog scale score, maternal, and fetal complications and patients' satisfaction were recorded. RESULTS: Patients receiving a combination of PCA remifentanil and DMET had a lower pain score compared with remifentanil alone in the second stage of labor (P = 0.001). The Total consumption of remifentanil was reduced by 53.3% in group I. There was an increased incidence of maternal complications and a lower patient satisfaction score in group II. CONCLUSION: DMET has an opioid sparing effect; a combination of DMET and remifentanil produces a synergistic effect that results in lower analgesic requirements and less maternal and neonatal adverse events. PMID- 26543464 TI - Femoral nerve block for acute pain relief in fracture shaft femur in an emergency ward. AB - BACKGROUND: Analgesia in patients with fracture shaft femur is usually insufficient as physician usually relies on parental analgesia in such situations. Local anesthetic blockade of femoral nerve to provide analgesia in fracture shaft femur is an under-used technique. We conducted a study to evaluate the efficacy of femoral nerve block (FNB) with 0.5% ropivacaine for acute pain relief in patients with fracture shaft femur. MATERIALS AND METHODS: A total of 50 patients were studied as they present in an emergency ward. All patients received an FNB with 15 ml of 0.5% ropivacaine. The onset of block, duration of analgesia, patient's acceptance after 24 h together with the effect of block were assessed. RESULTS: The onset of analgesia occurred in 5.34 +/- 1.10 min after the block. Pain scores decreased significantly from 9.12 +/- 0.9, preblock visual analog scale (VAS) score to 1.84 +/- 1.25, VAS score at 10 min after the block (P < 0.001). The quality of analgesia did not change when patient underwent radiological examination (38.9 +/- 5.22 min after block) and traction application (69.4 +/- 8.98 min after block). The duration of analgesia observed was 227 +/- 63.99 min. Patient acceptance after 24 h of FNB was good in 86% patients. There were no side effects. CONCLUSIONS: It was concluded that in the emergency ward, rapid, effective, and long lasting analgesia can be achieved by safe and simple FNB in patients with fracture shaft femur. PMID- 26543465 TI - Perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted gastric sleeve resection. AB - PURPOSE: One of the major advantages for patients undergoing minimally invasive surgery as compared to an open surgical procedure is the improved recovery profile and decreased opioid requirements in the perioperative period. There are no definitive studies comparing the analgesic requirements in patients undergoing two different types of minimally invasive procedure. This study retrospectively compares the perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted, laparoscopic gastric sleeve resection. MATERIALS AND METHODS: With Institutional Review Board approval, the medication administration records of all severely obese patients who underwent gastric sleeve resection were retrospectively reviewed. Intra operative analgesic and adjuvant medications administered, postoperative analgesic requirements, and visual analog pain scores were compared between those undergoing a laparoscopic procedure versus a robotic-assisted procedure. RESULTS: This study cohort included a total of 28 patients who underwent gastric sleeve resection surgery with 14 patients in the laparoscopic group and 14 patients in the robotic-assisted group. Intra-operative adjuvant administration of both intravenous acetaminophen and ketorolac was similar in both groups. Patients in the robotic-assisted group required significantly less opioid during the intra operative period as compared to patients in the laparoscopic group (0.15 +/- 0.08 mg/kg vs. 0.19 +/- 0.06 mg/kg morphine, P = 0.024). Cumulative opioid requirements for the first 72 postoperative h were similar in both the groups (0.64 +/- 0.25 vs. 0.68 +/- 0.27 mg/kg morphine, P = NS). No difference was noted in the postoperative pain scores. CONCLUSION: Although intraoperative opioid administration was lower in the robotic-assisted group, the postoperative opioid requirements, and the postoperative pain scores were similar in both groups. PMID- 26543466 TI - A prospective study to evaluate and compare laryngeal mask airway ProSeal and i gel airway in the prone position. AB - BACKGROUND: Prone position is commonly used to provide surgical access to a variety of surgeries. In view of the advantages of induction of anesthesia in the prone position, we conducted a randomized study to evaluate and compare ProSeal laryngeal mask airway (LMA) and i-gel in the prone position. MATERIALS AND METHODS: Totally, 40 patients of either sex as per American Society of Anesthesiologists physical status I or II, between 16 and 60 years of age, scheduled to undergo surgery in prone position were included in the study. After the patients positioned themselves prone on the operating table, anesthesia was induced by the standard technique. LMA ProSeal was used as an airway conduit in group 1 while i-gel was used in group 2. At the end of surgery, the airway device was removed in the same position. RESULTS: Insertion of airway device was successful in first attempt in 16, and 17 cases in ProSeal laryngeal mask airway (PLMA) and i-gel groups, respectively. A second attempt was required to secure the airway in 4 and 3 patients in PLMA and i-gel groups, respectively. The mean insertion time was 21.8 +/- 2.70 s for group 1 and 13.1 +/- 2.24 s for group 2, the difference being statistically significant (P < 0.05). The mean seal pressure in group 1 was 36 +/- 6.22 cm H2 O and in group 2 was 25.4 +/- 3.21 cm H2 O. The difference was statistically significant (P < 0.05). 13 patients in group 1 had fiberoptic bronchoscopy (FOB) grade 1 while it was 6 for group 2. The remaining patients in both groups had FOB grade 2. CONCLUSION: Insertion of supraglottic airways and conduct of anesthesia with them is feasible in the prone position. The PLMA has a better seal while insertion is easier with i-gel. PMID- 26543469 TI - Anesthetic management of an elderly patient with kyphoscoliosis and dilated cardiomyopathy posted for abdominal hysterectomy and salpingo-oophorectomy. AB - A 76-year-old kyphoscoliotic female patient presented with severe pain and sudden acute abdominal distension for 1-week and was diagnosed to have right-sided massive twisted ovarian cyst. The patient was a known case of hypertension, dilated cardiomyopathy with low 20% cardiac ejection fraction. Though very few incidences of multiple co-morbid conditions existing together in a single elderly patient have been reported in the past, it is important to titrate the dosage, type of anesthetic agents and their routes of administration in high risk patients. PMID- 26543467 TI - Etomidate in pediatric anesthesiology: Where are we now? AB - Etomidate is an intravenous anesthetic agent released for clinical use in the United States in 1972. Its popularity in clinical practice is the result of its beneficial effects on intracerebral dynamics with limited effects on hemodynamic function. These properties have made it a safe and effective anesthetic induction agent in both adult and pediatric patients with altered myocardial performance, congenial heart disease, or hypovolemia. However, recent concern has been expressed regarding its effects on the endogenous production of corticosteroids and the impact of that effect on patient outcomes. The following manuscript reviews clinical reports regarding etomidate use in the pediatric population and discusses recent concerns regarding its effects on corticosteroid metabolism and the implications of such effects for clinical use. PMID- 26543468 TI - Conflicts in operating room: Focus on causes and resolution. AB - The operation theater (OT) environment is the most complex and volatile workplace where two coequal physicians share responsibility of one patient. Difference in information, opinion, values, experience and interests between a surgeon and anesthesiologist may arise while working in high-pressure environments like OT, which may trigger conflict. Quality of patient care depends on effective teamwork for which multidisciplinary communication is an essential part. Troubled relationships leads to conflicts and conflicts leads to stressful work environment which hinders the safe discharge of patient care. Unresolved conflicts can harm the relationship but when handled in a positive way it provides an opportunity for growth and ultimately strengthening the bond between two people. By learning the skills to resolve conflict, we can keep our professional relationship healthy and strong which is an important component of good patient care. PMID- 26543470 TI - Transient bladder and fecal incontinence following epidural blood patch. AB - Epidural blood patch (EBP) is the currently accepted treatment of choice for postdural puncture headache because of its high initial success rates and infrequent complications. Many authors recommended a small volume (10-20 mL) of blood to be delivered for an effective EBP. Here, we report an obstetric patient who developed a transient bladder and fecal incontinence after 19 mL of blood EBP at L1 -L2 level. Since the magnetic resonance image did not demonstrate any definitive spinal cord lesion, the exact mechanism remains unclear. We suggest that accumulation of blood performed at L1 to L2 level in a closed relationship with the sacral cord, may have trigger a significant pressure elevation of the epidural space at this level, resulting in a temporal spinal cord-related injury in the sacral cord. PMID- 26543471 TI - Stellate ganglion pulsed radiofrequency ablation for stretch induced complex regional pain syndrome type II. AB - Complex regional pain syndrome (CRPS) following injury or nerve damage, as its name signifies, is a challenging entity, and its successful management requires a multidisciplinary approach. It not only manifests as severe pain, but also gives rise to functional disability, lack of sleep, lack of enjoyment of life and poor quality of life. Various pain interventional techniques have been described in the literature for the management of CRPS ranging from sympathetic blocks to spinal cord stimulator. A 34-year-old liver transplant donor, who developed position-induced right upper limb neuropathic pain suggestive of CRPS type II was managed initially with medications and later with stellate ganglion block under fluoroscopic guidance at cervical C7 position. Following an initial significant improvement in pain and allodynia, which was transient, a pulsed radiofrequency ablation of stellate ganglion was performed successfully to provide prolonged and sustained pain relief, which persisted up to 14 months of follow-up. PMID- 26543472 TI - Spinal anesthesia using Taylor's approach helps avoid general anesthesia in short stature asthmatic patient. AB - The case history of a 35-year-old female patient with short stature is presented. She was posted for rectopexy in view of rectal prolapse. She was a known case of bronchial asthma. She had crowding of intervertebral spaces, which made administration of spinal anesthesia via the normal route very difficult. Taylor's approach for administration of the same was tried and proved successful, thus saving the patient from receiving general anesthesia in the presence of bronchial asthma, for a perineal surgery. The possible cause for the difficulty in administration of spinal anesthesia and the Taylor's approach are discussed, and reports of similar cases reviewed. PMID- 26543473 TI - "Amber in chamber" an enigmatous right atrial mass in a neonate. AB - The incidence of fungal infection is increasing worldwide. Although fungal infection is common in adults, few cases have been reported in the neonatal population. We report a case of the preterm neonate of 34 weeks who developed respiratory distress on 2(nd) day and was initiated on mechanical ventilation. Treatment was instituted for sepsis, but the patient continued to deteriorate. Two-dimensional echocardiography revealed a large right atrial mass, which eventually turned out to be fungal ball. Intense surgical and medical management led to a speedy recovery of the patient. We stress on the early use of echocardiography in atypical presentation of neonatal septicemia along with routine investigations to help in early recognition of source of infection. This can be of great value in initiating definitive management and improving survival rate in such patients. PMID- 26543474 TI - Low tracheal tumor and airway management: An anesthetic challenge. AB - We describe a case presenting with tracheal tumor wherein a Microlaryngeal tube was advanced into the trachea distal to the tumor for primary airway control followed by cannulation of both endobronchial lumen with 5.5 mm endotracheal tubes to provide independent lung ventilation post tracheal transection using Y- connector attached to anesthesia machine. The plan was formulated to provide maximal surgical access to the trachea while providing adequate ventilation at the same time. A 32 yrs non smoker male, complaining of cough, progressive dyspnea and hemoptysis was diagnosed to have a broad based mass in the trachea on computed tomography of chest. Bronchoscopy of the upper airway confirmed presence of the mass at a distance of 9 cms from the vocal cords, obstructing the tracheal lumen by three fourth of the diameter. The patient was scheduled to undergo the resection of the mass through anterolateral thoracotomy. We recommend the use of extralong, soft, small sized microlaryngeal surgery tube in tumors proximal to carina, for securing the airway before the transection of trachea and bilateral endobronchial intubation with small sized cuffed endotracheal tubes for maintenance of ventilation after the transection of trachea in patients with mass in the lower trachea. PMID- 26543475 TI - Anesthetic management for bronchoscopy and debulking of obstructing intratracheal tumor. AB - Primary tracheal tumors comprise a rare group of benign and malignant tumors. Bronchoscopy is required for diagnosis and staging of tracheal neoplasms as well as debulking of the tumor. The management of anesthesia for rigid bronchoscopy in a patient with tracheal neoplasm presents with many challenges to the anesthetist. We present anesthetic management of an 18-year-old female who presented with orthopnea. Computed tomography scan of the thorax revealed a polypoidal lesion in the trachea proximal to carina and consolidation in the right middle lobe. The patient was scheduled for rigid bronchoscopy and debulking of the tumor. Case was successfully managed by providing positive pressure ventilation and oxygenation during rigid bronchoscopy using manual ventilation through the side port of the rigid bronchoscope. The procedure was uneventful, and patient improved symptomatically in the immediate postoperative period. The successful management of this case demonstrates the airway management in a patient with tracheal tumor for rigid bronchoscopy. PMID- 26543476 TI - Cardiac arrest following tourniquet release: Needs attention! PMID- 26543477 TI - Perioperative management in a case of glucose-6-phosphate dehydrogenase deficiency undergoing orthopaedic surgery. PMID- 26543478 TI - Sonopathology: An onco-intensivist in active search of serendipity. PMID- 26543479 TI - Anesthetic consideration in a patient with giant bilateral lung bullae with severe respiratory compromise. PMID- 26543480 TI - Erratum: Anesthetic management of craniosynostosis repair in patient with Apert syndrome: Erratum. AB - [This corrects the article on p. 399 in vol. 8, PMID: 25191197.]. PMID- 26543481 TI - Stability-Indicating Assay for the Determination of Pentobarbital Sodium in Liquid Formulations. AB - A stability-indicating assay by reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of pentobarbital sodium in oral formulations: a drug used for infant sedation in computed tomography (CT) or magnetic resonance imaging (MRI) scan. The chromatographic separation was achieved on a reversed-phase C18 column, using isocratic elution and a detector set at 214 nm. The optimized mobile phase consisted of a 0.01 M potassium buffer pH 3 and methanol (40 : 60, v/v). The flow rate was 1.0 mL/min and the run time of analysis was 5 min. The linearity of the method was demonstrated in the range of 5 to 250 MUg/mL pentobarbital sodium solution (r (2) = 0.999). The limit of detection and limit of quantification were 2.10 and 3.97 MUg/mL, respectively. The intraday and interday precisions were less than 2.1%. Accuracy of the method ranged from 99.2 to 101.3%. Stability studies indicate that the drug is stable to sunlight and in aqueous solution. Accelerated pentobarbital sodium breakdown by strong alkaline, acidic, or oxidative stress produced noninterfering peaks. This method allows accurate and reliable determination of pentobarbital sodium for drug stability assay in pharmaceutical studies. PMID- 26543483 TI - Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event. AB - Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide's metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes. PMID- 26543482 TI - Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate: A Histomorphometric Study in Humans. AB - Purpose. To investigate the regenerative results obtained with the association of bone marrow aspirate concentrate using the Bone Marrow Aspirate Concentrate (BMAC) method to a xenogeneic bone graft (Bio-Oss) in sinus floor elevation. Materials and Methods. Using a randomized controlled study design in eight consecutive patients (age of 55.4 +/- 9.2 years), 16 sinus floor lift procedures were performed with Bio-Oss alone (control group, CG, n = 8) or combined with bone marrow aspirate concentrate obtained via the BMAC method (test group, TG, n = 8). Six months after the grafting procedures, bone biopsies were harvested during implant placement and were analyzed by histomorphometry. Results. Histomorphometric analysis revealed a significantly higher amount (p < 0.05) of vital mineralized tissue in TG when compared to the CG (55.15 +/- 20.91% and 27.30 +/- 5.55%, resp.). For nonvital mineralized tissue, TG presented a statistically higher level of Bio-Oss resorption (p < 0.05) when compared with the CG (6.32 +/- 12.03% and 22.79 +/- 9.60%, resp.). Both groups (TG and CG) showed no significantly different levels (p > 0.05) of nonmineralized tissue (38.53 +/- 13.08% and 49.90 +/- 7.64%, resp.). Conclusion. The use of bone marrow concentrate obtained by BMAC method increased bone formation in sinus lift procedures. PMID- 26543484 TI - Subdural Empyema Complicating Bacterial Meningitis: A Challenging Diagnosis in a Patient with Polysubstance Abuse. AB - Subdural empyema (SDE) and cerebrovascular accident (CVA) are uncommon life threatening complications of bacterial meningitis, which require urgent neurosurgical intervention to prevent adverse outcomes. Clinicians must be vigilant of the onset of focal neurologic deficits or seizure activity to establish the diagnosis of SDE. Streptococcus pneumoniae accounts for <1% of pyogenic brain abscesses. This case describes a presentation of community acquired pneumococcal pneumonia in which the diagnosis of SDE with vasculitis induced CVA was confounded by concomitant substance abuse and sedation. PMID- 26543485 TI - Timing of first antenatal care attendance and associated factors among pregnant women in Arba Minch Town and Arba Minch District, Gamo Gofa Zone, south Ethiopia. AB - OBJECTIVE: To assess the timing of first antenatal care attendance and associated factors among pregnant women in Arba Minch Town and Arba Minch District, south Ethiopia. METHOD: Facility based cross-sectional study employing both quantitative and qualitative methods was conducted from February to March, 2014, in Arba Minch Town and Arba Minch District. Data were collected from 409 pregnant women attending antenatal care clinics in nine public health facilities using systematic random sampling. Analysis was done using SPSS version 20. Descriptive statistics and binary and multiple logistic regression analysis were done. RESULTS: The mean (SD+/-) age of the respondents was 26 +/- 5.5 years. The mean gestational age at first antenatal care attendance was 5 +/- 1.5 months. This study indicated that pregnant women with low monthly income (AOR = 4.9, CI: 1.71, 14.08), women who did not receive advise on when to start ANC (AOR = 3, CI: 1.48, 6.24), women with household food insecurity (AOR = 4.66, CI: 1.007, 21.59) and women with unplanned pregnancy (AOR = 4.49, CI: 2.16, 9.35) had higher odds of late antenatal care attendance compared with their counterparts. CONCLUSIONS: The study showed that majority of the pregnant women attended late for first antenatal care. Hence, providing health education on the timing of antenatal care is important. PMID- 26543486 TI - Nonoperative Korean Medicine Combination Therapy for Lumbar Spinal Stenosis: A Retrospective Case-Series Study. AB - This is a retrospective case series exploring the therapeutic benefits and harm of nonoperative Korean medicine combination therapy for lumbar spinal stenosis (LSS). The medical records of a total of 33 LSS patients, who were treated as inpatients at Mokhuri Neck and Back Hospital, Republic of Korea, from November 2010 to January 2012, were reviewed first and telephone survey on these patients was conducted after one year. Body acupuncture, pharmacoacupuncture, Chuna, and oral administration of herbal medicines were offered to all patients. A Visual analogue scale (VAS) of pain and the walking duration without pain were used to assess the patients during the approximately 1-month treatment period. The average VAS score of pain and the walking duration improved significantly; the VAS score decreased from 9 (SD, 1.15) to 2.75 (2.22) (p < 0.01), and the walking duration increased from 5.5 (6.66) to 16.75 (13.00) minutes (p < 0.01). No adverse event was reported during the treatment. In addition, the decreased pain level and improved function continued for over one year. Although we did not find definitive evidence, the study results suggest that KM combination therapy may be beneficial for decreasing pain and improving function in LSS patients and may produce comparatively few adverse events. PMID- 26543487 TI - Neuropharmacological Potential of Gastrodia elata Blume and Its Components. AB - Research has been conducted in various fields in an attempt to develop new therapeutic agents for incurable neurodegenerative diseases. Gastrodia elata Blume (GE), a traditional herbal medicine, has been used in neurological disorders as an anticonvulsant, analgesic, and sedative medication. Several neurodegenerative models are characterized by oxidative stress and inflammation in the brain, which lead to cell death via multiple extracellular and intracellular signaling pathways. The blockade of certain signaling cascades may represent a compensatory therapy for injured brain tissue. Antioxidative and anti inflammatory compounds isolated from natural resources have been investigated, as have various synthetic chemicals. Specifically, GE rhizome extract and its components have been shown to protect neuronal cells and recover brain function in various preclinical brain injury models by inhibiting oxidative stress and inflammatory responses. The present review discusses the neuroprotective potential of GE and its components and the related mechanisms; we also provide possible preventive and therapeutic strategies for neurodegenerative disorders using herbal resources. PMID- 26543488 TI - A Systematic and Narrative Review of Acupuncture Point Application Therapies in the Treatment of Allergic Rhinitis and Asthma during Dog Days. AB - Acupuncture point application therapies, including San-Fu-Tie and San-Fu-Jiu, have been widely employed to treat diseases with attacks in winter during dog days in China. The therapies combine Chinese herbal medicine and acupuncture points with the nature. However, the previous studies were reported to be unsystematic and incomplete. To develop a more comprehensive understanding of the effects of acupuncture point application therapies on allergic rhinitis and asthma, a systematic review of the literature up to 2015 was conducted. After filtering, eighteen randomized controlled trials (RCTs) involving 1,785 subjects were included. This systematic and narrative review shows that acupuncture point application therapies have been extensively applied in the treatment of allergic rhinitis and asthma with advantages of favorable treatment effect, convenient operation, receiving patients' good acceptability and compliance, and few side effects. Meanwhile, the study elaborated the operating process of San-Fu-Tie and San-Fu-Jiu in detail. The review may provide a reference for clinical application in future. However, the efficacy, safety, and mechanisms of San-Fu-Tie and San-Fu Jiu in treating the above diseases need to be validated by more well-designed and fully powered RCTs in a larger population of patients. PMID- 26543489 TI - Effects of Tai Chi and Walking Exercises on Weight Loss, Metabolic Syndrome Parameters, and Bone Mineral Density: A Cluster Randomized Controlled Trial. AB - Tai Chi and walking are both moderate-intensity physical activity (PA) that can be easily practiced in daily life. The objective of the study was to determine the effects of these two PAs on weight loss, metabolic syndrome parameters, and bone mineral density (BMD) in Chinese adults. We randomized 374 middle-aged subjects (45.8 +/- 5.3 years) into 12-week training (45 minutes per day, 5 days per week) of Tai Chi (n = 124) or self-paced walking (n = 121) or control group (n = 129). On average, Tai Chi and walking groups lost 0.50 and 0.76 kg of body weight and 0.47 and 0.59 kg of fat mass after intervention, respectively. The between-group difference of waist circumference (WC) and fasting blood glucose (FBG) was -3.7 cm and -0.18 mmol/L for Tai Chi versus control and -4.1 cm and 0.22 mmol/L for walking versus control. No significant differences were observed regarding lean mass, blood pressure, triglycerides, total cholesterol, high density and low-density lipoprotein cholesterol, and BMD compared to control. Change in lean mass, not fat mass or total weight loss, was significantly correlated to the change in BMD. Our results suggest that both of these two PAs can produce moderate weight loss and significantly improve the WC and FBG in Hong Kong Chinese adults, with no additional effects on BMD. PMID- 26543492 TI - Optimal Placement of Irradiation Sources in the Planning of Radiotherapy: Mathematical Models and Methods of Solving. AB - This paper proposes and analyses a mathematical model for the problem of distribution of a finite number of irradiation sources during radiotherapy in continuous environments to maximize the minimal cumulative effects. A new algorithm based on nondifferentiable optimization techniques has been developed to solve this problem. PMID- 26543491 TI - Understanding restriction factors and intrinsic immunity: insights and lessons from the primate lentiviruses. AB - Primate lentiviruses include the HIVs, HIV-1 and HIV-2; the SIVs, which are endemic to more than 40 species of nonhuman primates in Africa; and SIVmac, an AIDS-causing pathogen that emerged in US macaque colonies in the 1970s. Because of the worldwide spread of HIV and AIDS, primate lentiviruses have been intensively investigated for more than 30 years. Research on these viruses has played a leading role in the discovery and characterization of intrinsic immunity, and in particular the identification of several antiviral effectors (also known as restriction factors) including APOBEC3G, TRIM5alpha, BST 2/tetherin and SAMHD1. Comparative studies of the primate lentiviruses and their hosts have proven critical for understanding both the evolutionary significance and biological relevance of intrinsic immunity, and the role intrinsic immunity plays in governing viral host range and interspecies transmission of viruses in nature. PMID- 26543494 TI - ROC-Boosting: A Feature Selection Method for Health Identification Using Tongue Image. AB - OBJECTIVE: To select significant Haar-like features extracted from tongue images for health identification. MATERIALS AND METHODS: 1,322 tongue cases were included in this study. Health information and tongue images of each case were collected. Cases were classified into the following groups: group containing 148 cases diagnosed as health; group containing 332 cases diagnosed as ill based on health information, even though tongue image is normal; and group containing 842 cases diagnosed as ill. Haar-like features were extracted from tongue images. Then, we proposed a new boosting method in the ROC space for selecting significant features from the features extracted from these images. RESULTS: A total of 27 features were obtained from groups A, B, and C. Seven features were selected from groups A and B, while 25 features were selected from groups A and C. CONCLUSIONS: The selected features in this study were mainly obtained from the root, top, and side areas of the tongue. This is consistent with the tongue partitions employed in traditional Chinese medicine. These results provide scientific evidence to TCM tongue diagnosis for health identification. PMID- 26543493 TI - Temporal Identification of Dysregulated Genes and Pathways in Clear Cell Renal Cell Carcinoma Based on Systematic Tracking of Disrupted Modules. AB - OBJECTIVE: The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. METHODS: Firstly, normal and ccRCC PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, we identified altered modules using maximum weight bipartite matching and ranked them in nonincreasing order. Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test. RESULTS: We obtained 136, 576, 693, and 531 disrupted modules of ccRCC stages I, II, III, and IV, respectively. Gene composition analyses of altered modules revealed that there were 56 common genes (such as MAPK1, CCNA2, and GSTM3) existing in the four stages. Besides pathway enrichment analysis identified 5 common pathways (glutathione metabolism, cell cycle, alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, and metabolism of xenobiotics by cytochrome P450) across stages I, II, III, and IV. CONCLUSIONS: We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC. PMID- 26543490 TI - Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases. AB - Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. The possibility of high throughoutput screening using proteomic techniques, particularly redox proteomics, provide more comprehensive overview of the interaction of proteins, as well as the interplay among processes involved in neuroprotection. Here by introducing the hormetic dose response concept, the mechanistic foundations and applications to the field of neuroprotection, we discuss the emerging role of heat shock protein as prominent member of vitagene network in neuroprotection and redox proteomics as a tool for investigating redox modulation of stress responsive vitagenes. Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process. PMID- 26543495 TI - Perspectives in Intraoperative Diagnostics of Human Gliomas. AB - Amongst large a variety of oncological diseases, malignant gliomas represent one of the most severe types of tumors. They are also the most common type of the brain tumors and account for over half of the astrocytic tumors. According to different sources, the average life expectancy of patients with various glioblastomas varies between 10 and 12 months and that of patients with anaplastic astrocytic tumors between 20 and 24 months. Therefore, studies of the physiology of transformed glial cells are critical for the development of treatment methods. Modern medical approaches offer complex procedures, including the microsurgical tumor removal, radiotherapy, and chemotherapy, supplemented with photodynamic therapy and immunotherapy. The most radical of them is surgical resection, which allows removing the largest part of the tumor, reduces the intracranial hypertension, and minimizes the degree of neurological deficit. However, complete removal of the tumor remains impossible. The main limitations are insufficient visualization of glioma boundaries, due to its infiltrative growth, and the necessity to preserve healthy tissue. This review is devoted to the description of advantages and disadvantages of modern intraoperative diagnostics of human gliomas and highlights potential perspectives for development of their treatment. PMID- 26543496 TI - Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network. AB - Apoptosis is the process of programmed cell death (PCD) that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature. PMID- 26543497 TI - Comparative Transcriptomes and EVO-DEVO Studies Depending on Next Generation Sequencing. AB - High throughput technology has prompted the progressive omics studies, including genomics and transcriptomics. We have reviewed the improvement of comparative omic studies, which are attributed to the high throughput measurement of next generation sequencing technology. Comparative genomics have been successfully applied to evolution analysis while comparative transcriptomics are adopted in comparison of expression profile from two subjects by differential expression or differential coexpression, which enables their application in evolutionary developmental biology (EVO-DEVO) studies. EVO-DEVO studies focus on the evolutionary pressure affecting the morphogenesis of development and previous works have been conducted to illustrate the most conserved stages during embryonic development. Old measurements of these studies are based on the morphological similarity from macro view and new technology enables the micro detection of similarity in molecular mechanism. Evolutionary model of embryo development, which includes the "funnel-like" model and the "hourglass" model, has been evaluated by combination of these new comparative transcriptomic methods with prior comparative genomic information. Although the technology has promoted the EVO-DEVO studies into a new era, technological and material limitation still exist and further investigations require more subtle study design and procedure. PMID- 26543498 TI - Risk factors for rod fracture after posterior correction of adult spinal deformity with osteotomy: a retrospective case-series. AB - BACKGROUND: Osteotomies including pedicle subtraction (PSO) and/or Smith-Peterson (SPO) are used to facilitate surgical correction of adult spinal deformity (ASD), but are associated with complications including instrumentation failure and rod fracture (RF). The purpose of this study was to determine incidence and risk factors for RF, including a clinically significant subset (CSRF), after osteotomy for ASD. METHODS: A retrospective review of clinical records was conducted on consecutive ASD patients treated with posterolateral instrumented fusion and osteotomy. Seventy-five patients (50 female; average age, 59) met strict inclusion/exclusion criteria and follow-up of >=1 year. Data was extracted pertaining to the following variables: patient demographics; details of surgical intervention; instrumentation; and postoperative outcomes. Patients were divided into two subgroups: 1) rod fracture (RF) and 2) non-RF. The RF subgroup was further divided into CSRF and non-CSRF. Odds ratios (OR) were calculated to evaluate the association between risk factors and RF. The chi (2)-test was used to define P-values for categorical variables, and T-test was applied for continuous variables, P-values <=0.05 were considered significant. RESULTS: Incidence rates of RF were: for entire population, 9.3 % (95 % Cl: 2.7 %; 15.9 %); for PSO, 16.2 % (95 % Cl: 4.3; 28.1); and for SPO, 2.6 % (95 % Cl: 0 %; 7.7 %); the OR of PSO versus SPO was 7.2 (95 % Cl: 0.8; 62.7, P = 0.1). CSRF incidence was 5.3 % (95 % CI: 0.2 %; 10.4 %). Significant risk of RF was revealed for following factors: fusion construct crossing both thoracolumbar and lumbosacral junctions (OR = 9.1, P = 0.05), sagittal rod contour >60 degrees (OR = 10.0, P = 0.04); the presence of dominos and/or parallel connectors at date of rod fracture (OR = 10.0, P = 0.01); and pseudarthrosis at >=1 year follow-up (OR = 28.9, P < 0.001). Statistically significant risk of CSRF was revealed for fusion to pelvis (P = 0.05) and pseudarthrosis at >=1 year follow-up (OR = 50.3, CI: 4.2; 598.8, P < 0.01). CONCLUSIONS: The risk of RF after posterolateral instrumented correction of ASD with osteotomy had statistically significant association with the following factors: pseudarthrosis at >=1 year follow-up; sagittal rod contour >60 degrees ; presence of dominos and/or parallel connectors at date of fracture; and fusion construct crossing both thoracolumbar and lumbosacral junctions. Statistically significant risk for the CSRF subset was fusion to the pelvis and pseudarthrosis at >=1 year follow-up. PMID- 26543499 TI - A comparison between survival from cancer before and after a physical traumatic injury: physical trauma before cancer is associated with decreased survival. AB - BACKGROUND: Prior traumatic experiences have been associated with poorer coping strategies, greater distress, and more posttraumatic stress disorder (PTSD) symptoms following a subsequent cancer diagnosis affecting their survival. However, the impact of prior physical traumatic injury on cancer survival has not been examined. METHODS: The present study matched patients from the same Level 1 Trauma center who appeared in both the trauma and cancer registries. A total of 498 patients met the criteria between 1998 and 2014 who have experienced both a diagnosis of cancer and a physical traumatic injury. The survival between the patients who had physical trauma before cancer (TBC) versus those that had physical trauma after the cancer diagnosis (TAC) were compared. RESULTS: The TBC group had a higher percentage of males (48 % vs 33 % p = 0.001) and motor vehicle collisions (18 % vs 7 %, p < 0.001), than the TAC group. TBC patients were also significantly younger than TAC patients at the time of the physical traumatic event (68.7 +/- 14.6 vs 76.2 +/- 12.0 years, p < 0.001), and longer length of time between the cancer diagnosis and physical traumatic injury (2.9 +/- 2.9 vs 1.7 +/- 2.6 years, p < 0.001). The overall probability of survival for the entire sample was 68 %. Percent survival for the TBC (n = 251) and TAC (n = 247) groups was 56 and 80 % respectively (p < 0.001). Results were consistent regardless of stage of cancer at diagnosis (hazard ratio (HR (Standard Error)). After adjusting for comorbidities Charlson comorbidity index (CCI) (HR = 1.2 (0.06), p = 0.009)), cancer stage (HR = 2.8 (0.12), p < 0.001)), lung cancer (HR = 1.7 (0.25), p < 0.001) and bladder cancer (HR = 3.5 (0.55), p = 0.02), experiencing a prior physical traumatic injury was associated with an increased HR for mortality of 4.6 (0.93), p < 0.001). CONCLUSIONS: A physical traumatic episode before cancer diagnosis (TBC) increased the risk of death 4.6 fold compared to the TAC group even after adjusting for CCI, stage of cancer at diagnosis, lung cancer, and bladder cancer. These findings suggest considering a history of physical traumatic injury in cancer patients as a possible risk factor for faster cancer progression and mortality. PMID- 26543500 TI - Correlates and Predictors of Psychological Distress among Afghan Refugees in San Diego County. AB - The psychological effects of war and resulting displacement continue to negatively impact Afghan refugees. The purpose of this study was to investigate factors that are associated with and predict psychological distress symptoms among Afghan refugees. We analyzed data from a diverse sample of 130 Afghan refugees recruited through non-random sampling in the San Diego area. Participants completed self-report questionnaires consisting of a culturally validated measure of psychological distress, the Afghan Symptom Checklist [ASCL] alongside standardized measures of acculturation, social support, and perceived stress. In bivariate analyses, older age, older age at migration, female gender, being widowed, having lower education, being unemployed, unable to comfortably pay monthly bills, lower acculturation and social support, and higher levels of perceived stress were associated with psychological distress. However, only few variables - female gender, being widowed, unable to comfortably pay monthly bills, and perceived stress - remained significant in multivariate analysis. The findings from this study contribute to understanding the social determinants of distress that affect Afghans in exile even after long-term resettlement in the US. These reported outcomes support the need for continued research with Afghans, alongside the implementation of culturally relevant psychosocial interventions that emphasize prevention of post-resettlement stressors immediately upon resettlement. PMID- 26543501 TI - Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid short- and branched-chain alkyl esters biodiesel. AB - BACKGROUND: Biodiesel is a mixture of fatty acid short-chain alkyl esters of different fatty acid carbon chain lengths. However, while fatty acid methyl or ethyl esters are useful biodiesel produced commercially, fatty acid esters with branched-chain alcohol moieties have superior fuel properties. Crucially, this includes improved cold flow characteristics, as one of the major problems associated with biodiesel use is poor low-temperature flow properties. Hence, microbial production as a renewable, nontoxic and scalable method to produce fatty acid esters with branched-chain alcohol moieties from biomass is critical. RESULTS: We engineered Saccharomyces cerevisiae to produce fatty acid short- and branched-chain alkyl esters, including ethyl, isobutyl, isoamyl and active amyl esters using endogenously synthesized fatty acids and alcohols. Two wax ester synthase genes (ws2 and Maqu_0168 from Marinobacter sp.) were cloned and expressed. Both enzymes were found to catalyze the formation of fatty acid esters, with different alcohol preferences. To boost the ability of S. cerevisiae to produce the aforementioned esters, negative regulators of the INO1 gene in phospholipid metabolism, Rpd3 and Opi1, were deleted to increase flux towards fatty acyl-CoAs. In addition, five isobutanol pathway enzymes (Ilv2, Ilv5, Ilv3, Aro10, and Adh7) targeted into the mitochondria were overexpressed to enhance production of alcohol precursors. By combining these engineering strategies with high-cell-density fermentation, over 230 mg/L fatty acid short- and branched chain alkyl esters were produced, which is the highest titer reported in yeast to date. CONCLUSIONS: In this work, we engineered the metabolism of S. cerevisiae to produce biodiesels in the form of fatty acid short- and branched-chain alkyl esters, including ethyl, isobutyl, isoamyl and active amyl esters. To our knowledge, this is the first report of the production of fatty acid isobutyl and active amyl esters in S. cerevisiae. Our findings will be useful for engineering S. cerevisiae strains toward high-level and sustainable biodiesel production. PMID- 26543502 TI - Influence of corn oil recovery on life-cycle greenhouse gas emissions of corn ethanol and corn oil biodiesel. AB - BACKGROUND: Corn oil recovery and conversion to biodiesel has been widely adopted at corn ethanol plants recently. The US EPA has projected 2.6 billion liters of biodiesel will be produced from corn oil in 2022. Corn oil biodiesel may qualify for federal renewable identification number (RIN) credits under the Renewable Fuel Standard, as well as for low greenhouse gas (GHG) emission intensity credits under California's Low Carbon Fuel Standard. Because multiple products [ethanol, biodiesel, and distiller's grain with solubles (DGS)] are produced from one feedstock (corn), however, a careful co-product treatment approach is required to accurately estimate GHG intensities of both ethanol and corn oil biodiesel and to avoid double counting of benefits associated with corn oil biodiesel production. RESULTS: This study develops four co-product treatment methods: (1) displacement, (2) marginal, (3) hybrid allocation, and (4) process-level energy allocation. Life-cycle GHG emissions for corn oil biodiesel were more sensitive to the choice of co-product allocation method because significantly less corn oil biodiesel is produced than corn ethanol at a dry mill. Corn ethanol life-cycle GHG emissions with the displacement, marginal, and hybrid allocation approaches are similar (61, 62, and 59 g CO2e/MJ, respectively). Although corn ethanol and DGS share upstream farming and conversion burdens in both the hybrid and process-level energy allocation methods, DGS bears a higher burden in the latter because it has lower energy content per selling price as compared to corn ethanol. As a result, with the process-level allocation approach, ethanol's life-cycle GHG emissions are lower at 46 g CO2e/MJ. Corn oil biodiesel life-cycle GHG emissions from the marginal, hybrid allocation, and process-level energy allocation methods were 14, 59, and 45 g CO2e/MJ, respectively. Sensitivity analyses were conducted to investigate the influence corn oil yield, soy biodiesel, and defatted DGS displacement credits, and energy consumption for corn oil production and corn oil biodiesel production. CONCLUSIONS: This study's results demonstrate that co product treatment methodology strongly influences corn oil biodiesel life-cycle GHG emissions and can affect how this fuel is treated under the Renewable Fuel and Low Carbon Fuel Standards. PMID- 26543503 TI - Erratum to: Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review. AB - [This corrects the article DOI: 10.1186/s13047-015-0114-5.]. PMID- 26543504 TI - Correlates of functional ankle instability in children and adolescents with Charcot-Marie-Tooth disease. AB - BACKGROUND: Functional ankle instability (FAI) is commonly reported by children and adolescents with Charcot-Marie-Tooth disease (CMT), however,, the specific variables associated with FAI remain unknown. An improved understanding of these variables may suggest interventions to improve ankle stability and possibly prevent the long-term complications associated with ankle instability in this population. The aim of this study was to therefore investigate the relationship between FAI and other functional, structural, anthropometric and demographic characteristics in a cross sectional sample of children and adolescents with CMT. METHODS: Thirty children and adolescents with CMT aged 7-18 years were recruited from the Peripheral Neuropathy Clinics of a large tertiary paediatric hospital. Measures of FAI were obtained using the Cumberland Ankle Instability Tool (CAIT). Demographic and anthropometric data was also collected. Other variables collected included foot structure (Foot Posture Index), ankle range of motion (weight bearing lunge) and functional parameters (balance, timed motor function and falls). Descriptive statistics were calculated to characterise the participants. Pearson's correlation coefficients were calculated to investigate the correlates of right and left FAI and demographic (age), anthropometric (height, weight, BMI), foot/ankle (foot structure and ankle flexibility) and functional parameters (balance task, timed motor function and falls frequency). Point biserial correlation was employed to correlate gender with right and left FAI. RESULTS: All but one study participant (n = 29) reported moderate to severe bilateral FAI with females reporting significantly greater ankle instability than males. FAI was significantly associated with cavus foot structure (r = .69, P < .001), female gender (r = -.47, P < .001) and impaired balance (r = .50, P < .001). CONCLUSIONS: This study confirms FAI is common in children and adolescents with CMT. An examination of the correlates of FAI suggests interventions, which target balance, and normalise foot structure should be explored to evaluate whether they might help to improve ankle stability in this population. PMID- 26543506 TI - Using virtual worlds for patient and public engagement. AB - Patient and public involvement is fundamental in healthcare and many methods attempt to facilitate this engagement. The present study investigated use of computer-generated environments known as 'virtual worlds' (VW) as an involvement method. The VW used in the present research was Second Life, which is 3 dimensional, publically accessible and internet-based. It is accessed using digital self-representations, or 'avatars', through which users navigate the virtual environment and communicate with one another. Participants were patients with long-term conditions, frequently involved in shaping health research and care. Some had mobility and communication difficulties, potentially making involvement through traditional face-to-face modes of engagement challenging. There were 2 stages to this study. Stage-1: Participants were introduced to VWs and Second Life. This was followed by a face-to-face focus group discussion (FGD) in order to gain their views on use of SL. Stage-2: An FGD attended by 8 people (4 patients, 3 researchers, 1 healthcare professional) was conducted in Second Life. Training and support on using Second Life had been provided for participants. The FGD took place successfully, although some technical and communication difficulties were experienced. Data was collected in the form of interviews and questionnaires from the patients about their experience of using the virtual world. Participants recognised the potential of VWs as a platform for patient engagement, especially for those who suffer from chronic conditions that impact severely upon their mobility and communication. Participant feedback indicated that potential barriers include technical problems with VW programs and potential user inexperience of using VWs, which may be counteracted by ensuring provision of continuous training and support. In conclusion, this study established the feasibility of using VWs for patient FGDs and indicates a potential of use of VWs for engagement in future, particularly for peer-led support and to engage people with particular long-term conditions. PMID- 26543508 TI - Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats. AB - BACKGROUND: Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. OBJECTIVE: To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. METHODS: Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. RESULTS: The treatment with Arctium lappa extract reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase in the acetaminophen group when compared with the control group. DNA fragments in the acetaminophen-injected group were also significantly increased (P < 0.05). The comet assay revealed increased detaching tail length and DNA concentration during the hepatic toxicity in the acetaminophen group. The malondialdehyde content was inhibited by Arctium lappa treatment (12.97+/-0.89 nmol/mg) when compared with the acetaminophen-treated-only group (12.97+/-0.89 nmol/mg). Histopathologic examination revealed that acetaminophen administration produced hepatic cell necrosis, infiltrate of lymphocytes, and vacuolation that were associated with the acetaminophen-treated animal group, but the degree of acetaminophen-induced hepatotoxicity was mediated by treatment with Arctium lappa extract. CONCLUSIONS: Arctium lappa can prevent most of the hepatic tissue damage caused by acetaminophen overdose in rats. PMID- 26543505 TI - Neuron-astrocyte interactions in neurodegenerative diseases: Role of neuroinflammation. AB - Selective neuron loss in discrete brain regions is a hallmark of various neurodegenerative disorders, although the mechanisms responsible for this regional vulnerability of neurons remain largely unknown. Earlier studies attributed neuron dysfunction and eventual loss during neurodegenerative diseases as exclusively cell autonomous. Although cell-intrinsic factors are one critical aspect in dictating neuron death, recent evidence also supports the involvement of other central nervous system cell types in propagating non-cell autonomous neuronal injury during neurodegenerative diseases. One such example is astrocytes, which support neuronal and synaptic function, but can also contribute to neuroinflammatory processes through robust chemokine secretion. Indeed, aberrations in astrocyte function have been shown to negatively impact neuronal integrity in several neurological diseases. The present review focuses on neuroinflammatory paradigms influenced by neuron-astrocyte cross-talk in the context of select neurodegenerative diseases. PMID- 26543509 TI - Pill Properties that Cause Dysphagia and Treatment Failure. AB - BACKGROUND: Pills (tablets and capsules) are widely used to administer prescription drugs or to take supplements such as vitamins. Unfortunately, little is known about how much effort it takes Americans to swallow these various pills. More specifically, it is not known to what extent hard-to-swallow pills might affect treatment outcomes (eg, interfering with adherence to prescribed medications or causing clinical complications). It is also unclear which properties (eg, size, shape, or surface texture) Americans prefer or reject for their pills. To learn more about these issues, we interviewed a small group of individuals. METHODS: We invited individuals in waiting rooms of our tertiary health care center to participate in structured interviews about their pill taking habits and any problems they have swallowing pills. We inquired which pill properties they believed caused swallowing problems. Participants scored capsules and pills of representative size, shape, and texture for swallowing effort and reported their personal preferences. RESULTS: Of 100 successive individuals, 99 participants completed the interview (65% women, mean age = 41 years, range = 23 77 years). Eighty-three percent took pills daily (mean 4 pills/d; 56% of those pills were prescribed by providers). Fifty-four percent of participants replied yes to the question, "Did you ever have to swallow a solid medication that was too difficult?" Four percent recounted serious complications: 1% pill esophagitis, 1% pill impaction, and 2% stopped treatments (antibiotic and prenatal supplement) because they could not swallow the prescribed pills. Half of all participants routinely resorted to special techniques (eg, plenty of liquids or repeated or forceful swallows). Sixty-one percent of those having difficulties cited specific pill properties: 27% blamed size (20% of problems were caused by pills that were too large whereas 7% complained about pills that were too small to sense); 12% faulted rough surface texture; others cited sharp edges, odd shapes, or bad taste/smell. Extra-large pills were widely loathed, with 4 out of 5 participants preferring to take 3 or more medium-sized pills instead of a single jumbo pill. CONCLUSIONS: Our survey results suggest that 4 out of 5 adult Americans take several pills daily, and do so without undue effort. It also suggests that half of today's Americans encounter pills that are hard to swallow. Up to 4% of our participants gave up on treatments because they could not swallow the prescribed pills. Up to 7% categorically rejected taking pills that are hard to swallow. Specific material properties are widely blamed for making pills hard to swallow; extra-large capsules and tablets are universally feared, whereas medium-sized pills with a smooth coating are widely preferred. Our findings suggest that health care providers could minimize treatment failures and complications by prescribing and dispensing pills that are easy to swallow. Industry and regulatory bodies may facilitate this by making swallowability an essential criterion in the design and licensing of oral medications. Such policies could lessen the burden of pill taking for Americans and improve the adherence with prescribed treatments. PMID- 26543507 TI - Histone acetylation: novel target for the treatment of acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL) has been generally considered a genetic disease (disorder) with an aggressive tumor entity of highly proliferative malignant lymphoid cells. However, in recent years, significant advances have been made in the elucidation of the ALL-associated processes. Thus, we understand that histone acetylation is involved in the permanent changes of gene expression controlling ALL developmental outcomes. In this article, we will focus on histone acetylation associated with ALL, their implications as biomarkers for prognostic, and their preclinical and clinical applications. PMID- 26543510 TI - Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population. AB - BACKGROUND: Insulin resistance heightens the risk for type 2 diabetes mellitus and cardiovascular disease. Amelioration of insulin resistance may reduce this risk. The thiazolidinedone class of insulin sensitizers improves insulin action in individuals with insulin-resistant diabetes and nondiabetic individuals. However, there are few reports on the time of onset of such effects independent of reversal of glucotoxicity. OBJECTIVE: The goal of our study was to test whether the thiazolidinedione pioglitazone has prominent early metabolic effects that can be detected in an obese, nondiabetic, insulin-resistant population. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group trial in men with nondiabetic insulin resistance using a hyperinsulinemic euglycemic clamp technique (at low and high doses of insulin at 10 and 40 mU/m(2)/min, respectively). The patients were given 30 mg daily oral pioglitazone or placebo for 28 days. Patients underwent a baseline clamp before initiation of treatment, and again at 14 and 28 days of treatment. RESULTS: Compared with placebo, under high-dose hyperinsulinemia, pioglitazone led to significant increases in glucose disposal rates (GDR) of 1.29 mg/kg/min (90% CI, 0.43-2.15; 39%; P=0.008) that were detectable at 2 weeks of treatment and persisted at 4 weeks of treatment. Under low-dose hyperinsulinemia, significant increases in GDR of 0.40 mg/kg/min (90% CI, 0.17-0.62; 95%; P=0.003) were observed at 4 weeks of treatment. These responses were accompanied by robust suppression of free fatty acids under hyperinsulinemic conditions, and by significant increases in circulating basal total adiponectin at 2 and 4 weeks of treatment. CONCLUSIONS: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712. PMID- 26543511 TI - Spontaneous Isolated Celiac Artery and Superior Mesenteric Artery Dissections: A Rare Case. AB - BACKGROUND: Arterial dissection is defined as the cleavage of the arterial wall by an intramural hematoma. Reports of dissection of the celiac and/or superior mesenteric artery are rare; as far as we know, only 24 cases of spontaneous isolated celiac trunk dissection, and 71 cases of spontaneous isolated superior mesenteric artery dissection have been reported. CASE REPORT: The case presents a 48-year-old male with a sudden-onset epigastric pain. A Computed Tomography Angiography of the thoracoabdominal aorta was applied and dissections of both the celiac artery and SMA were determined. A conservative therapeutic approach was preferred and the patient was discharged with anticoagulant and antihypertensive therapy. CONCLUSIONS: Although rare, spontaneous isolated celiac artery and superior mesenteric artery dissections must be kept in mind in the differential diagnosis of the epigastric pain in the emergency room. Contrast-enhanced Computed Tomography Angiography examination is the method of choice in the diagnosis. PMID- 26543512 TI - The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children. AB - BACKGROUND: In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. MATERIAL/METHODS: The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. RESULTS: Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the fragments, were 3 times more common in girls. Statistical analysis of the measurements of length and width of the callus demonstrated that the differences between results obtained in the ultrasound in comparison with X-rays were not statistically significant. Moreover, preliminary results showed a significantly higher degree of vascularization of the callus than of the healthy periosteum. CONCLUSIONS: Preliminary results indicate the high efficacy of ultrasound in the evaluation of callus formation after fractures of long bones in children and the possibility of its alternative use to X-ray examinations. PMID- 26543513 TI - An integrated microfluidic system for screening of phage-displayed peptides specific to colon cancer cells and colon cancer stem cells. AB - Affinity reagents recognizing biomarkers specifically are essential components of clinical diagnostics and target therapeutics. However, conventional methods for screening of these reagents often have drawbacks such as large reagent consumption, the labor-intensive or time-consuming procedures, and the involvement of bulky or expensive equipment. Alternatively, microfluidic platforms could potentially automate the screening process within a shorter period of time and reduce reagent and sample consumption dramatically. It has been demonstrated recently that a subpopulation of tumor cells known as cancer stem cells possess high drug resistance and proliferation potential and are regarded as the main cause of metastasis. Therefore, a peptide that recognizes cancer stem cells and differentiates them from other cancer cells will be extremely useful in early diagnosis and target therapy. This study utilized M13 phage display technology to identify peptides that bind, respectively, to colon cancer cells and colon cancer stem cells using an integrated microfluidic system. In addition to positive selection, a negative selection process was integrated on the chip to achieve the selection of peptides of high affinity and specificity. We successfully screened three peptides specific to colon cancer cells and colon cancer stem cells, namely, HOLC-1, HOLC-2, and COLC-1, respectively, and their specificity was measured by the capture rate between target, control, and other cell lines. The capture rates are 43.40 +/- 7.23%, 45.16 +/- 7.12%, and 49.79 +/- 5.34% for colon cancer cells and colon cancer stem cells, respectively, showing a higher specificity on target cells than on control and other cell lines. The developed technique may be promising for early diagnosis of cancer cells and target therapeutics. PMID- 26543514 TI - Contactless microfluidic pumping using microchannel-integrated carbon black composite membranes. AB - The ability to pump and manipulate fluid at the micron-scale is a basic requirement for microfluidic platforms. Many current manipulation methods, however, require expensive and bulky external supporting equipment, which are not typically compatible for portable applications. We have developed a contactless metal electro-osmotic micropump capable of pumping conductive buffers. The pump operates using two pairs of gallium metal electrodes, which are activated using an external voltage source and separated from a main flow channel by a thin micron-scale polydimethylsiloxane (PDMS) membrane. The thin contactless membrane allows for field penetration and electro-osmotic flow within the microchannel, but eliminates electrode damage and sample contamination commonly associated with traditional DC electro-osmotic pumps that utilize electrodes in direct contact with the working fluid. Our previous work has demonstrated the effectiveness of this method in pumping deionized water. However, due to the high resistivity of PDMS, this method proved difficult to apply towards manipulating conductive buffers. To overcome this limitation, we fabricated conductive carbon black (CB) powder directly into the contactless PDMS membranes. The increased electrical conductivity of the contactless PDMS membrane significantly increased micropump performance. Using a microfluidic T-channel device and an electro-osmotic flow model, we determined the influence that CB has on pump pressure for CB weight percents varying between 0 and 20. The results demonstrate that the CB increases pump pressure by two orders of magnitude and enables effective operations with conductive buffers. PMID- 26543515 TI - Geometrical optimization of microstripe arrays for microbead magnetophoresis. AB - Manipulation of magnetic beads plays an increasingly important role in molecular diagnostics. Magnetophoresis is a promising technique for selective transportation of magnetic beads in lab-on-a-chip systems. We investigate periodic arrays of exchange-biased permalloy microstripes fabricated using a single lithography step. Magnetic beads can be continuously moved across such arrays by combining the spatially periodic magnetic field from microstripes with a rotating external magnetic field. By measuring and modeling the magnetophoresis properties of thirteen different stripe designs, we study the effect of the stripe geometry on the magnetophoretic transport properties of the magnetic microbeads between the stripes. We show that a symmetric geometry with equal width of and spacing between the microstripes facilitates faster transportation and that the optimal period of the periodic stripe array is approximately three times the height of the bead center over the microstripes. PMID- 26543516 TI - Integrative Health and Healing as the New Health Care Paradigm for the Military. AB - Background: The field of integrative health and healing (IH2) is emerging out of the dark recesses of "voodoo" stereotypes and into the light as a new and much needed health care paradigm. It is a philosophy of health and healing that seeks to place patients as the preeminent players in health management, disease prevention, and injury recovery. There is an emphasis of patient responsibility, which includes a holistic approach that merges allopathic with complementary medicine. Objective: The aim of this article is to explore the historical origins of integrative medicine and investigate the future role of the IH2 paradigm. Methods: This article reviews current available data and information regarding complementary and alternative medicine utilized in civilian and military populations as the basis for a new paradigm for a system of care-a system that empowers patients. Conclusions: The current U.S. health care system is reactive and disease-based, with a focus on reductionism. This system is not serving us well. IH2 is a new model of cost-effective patient-centered health care. PMID- 26543517 TI - Overview of Integrative Medicine Practices and Policies in NATO Participant Countries. AB - Background: CAMbrella is a European research network for complementary and alternative medicine (CAM). Between January 2010 and December 2013 the CAMbrella consortium reviewed the status of CAM in Europe from the perspectives of: (1) terminology for description; (2) citizens' needs and expectations; (3) patients' usage patterns; (4) providers' practice patterns; and (5) regulatory and legal status in Europe. Together, this data was used to form a set of recommendations to the European Commission, the European Parliament, and national policy makers and civil society stakeholders. These recommendations can serve as a roadmap for European CAM research. Objective: This article aims to inform the reader about CAM prevalence, usage perspectives, and the future roadmap for CAM practices and research within the European Union. Method: This overview describes CAM status in the European Union, using the CAMbrella consortium projects as the source of information. Conclusions: The North Atlantic Treaty Organization is positioned as a potential foundation for inclusion of CAM modalities within the militaries as well for as collaborative research on safe and cost-effective practices. PMID- 26543518 TI - Integrative Medicine Experience in the U.S. Department of Defense. AB - Background: Over the past 15 years, the use of complementary and alternative medicine (CAM) services, currently described as integrative medicine (IM) when used together with conventional medicine , has continued to rise in the United States. The trends seen in the civilian population are mirrored within the U.S. Military. Objective: A survey was conducted to show the change in the prevalence of integrative medicine services, budgeting of those services, and ongoing research in IM within Department of Defense (DoD) medical treatment facilities (MTFs) from 2005 through 2009. Materials and Methods:Design: The Deputy Chief of Clinical Services or Service equivalent was contacted at fourteen selected DoD MTFs. Comprehensive structured telephone interviews were conducted using a formatted 20-item questionnaire. The questionnaire design was of a mixed model with open and closed formats as well as dichotomous yes/no questions. The questions covered the subject areas of available services, budgeting, and research. The initial survey was conducted in 2005 with a follow-up survey conducted in 2009. Setting: This survey involved DoD MTFs. Main Outcome Measures: The surveys were conducted to determine the prevalence of IM services within selected DoD facilities. Results: There was a steady increase in the number of IM services available in the DoD MTFs from 2005 through 2009. Acupuncture, biofeedback, nutritional counseling, and spiritual healing were the most prevalent IM services in 2009. Funding sources changed from central funding (Offices of the Surgeon General) to Congressional and local funding. Conclusions: It is essential that the DoD medical community provides safe and effective treatments by providing oversight of IM services, collaboration for research, credentialing of practitioners, and establishing educational programs. PMID- 26543519 TI - Modeling Multiple Responses via Bootstrapping Margins with an Application to Genetic Association Testing. AB - The need for analysis of multiple responses arises from many applications. In behavioral science, for example, comorbidity is a common phenomenon where multiple disorders occur in the same person. The advantage of jointly analyzing multiple correlated responses has been examined and documented. Due to the difficulties of modeling multiple responses, nonparametric tests such as generalized Kendall's Tau have been developed to assess the association between multiple responses and risk factors. These procedures have been applied to genomewide association studies of multiple complex traits. Unfortunately, those nonparametric tests only provide the significance of the association but not the magnitude. We propose a Gaussian copula model with discrete margins for modeling multivariate binary responses. This model separates marginal effects from between trait correlations. We use a bootstrapping margins approach to constructing Wald's statistic for the association test. Although our derivation is based on the fully parametric Gaussian copula framework for simplicity, the underlying assumptions to apply our method can be weakened. The bootstrapping margins approach only requires the correct specification of the model margins. Our simulation and real data analysis demonstrate that our proposed method not only increases power over some existing association tests, but also provides further insight into genetic association studies of multivariate traits. PMID- 26543521 TI - When Societal Norms and Social Identity Collide: the Race Talk Dilemma for Racial Minority Children. AB - Racial minorities face a unique "race talk" dilemma in contemporary American society: their racial background is often integral to their identity and how others perceive them, yet talk of race is taboo. This dilemma highlights the conflict between two fundamental social processes: social identity development and social norm adherence. To examine how, and with what costs, this dilemma is resolved, 9-12-year-old Latino, Asian, Black, and White children (n=108) completed a photo identification task in which acknowledging racial difference is beneficial to performance. Results indicate minority children are just as likely to avoid race as White children, and such avoidance exacted a cost to performance and nonverbal comfort. Results suggest that teachers are particularly important social referents for instilling norms regarding race. Norms that equate colorblindness with socially appropriate behavior appear more broadly influential than previously thought, stifling talk of race even among those for whom it may be most meaningful. PMID- 26543522 TI - Comparison of Methicillin Resistant Staphylococcus Aureus in Healthy Community Hospital Visitors [CA-MRSA] and Hospital Staff [HA-MRSA]. AB - BACKGROUND: The prevalence of community-associated methicillin-resistant Staphylococcus aureus [CA-MRSA] is unknown in Oman. METHODS: Nasal and cell phones swabs were collected from hospital visitors and health-care workers on sterile polyester swabs and directly inoculated onto a mannitol salt agar containing oxacillin, allowing growth of methicillin-resistant microorganisms. Antibiotic susceptibility tests were performed using Kirby Bauer's disc diffusion method on the isolates. Minimum inhibitory concentration (MIC) was determined for vancomycin and teicoplanin against the resistant isolates of MRSA by the Epsilometer [E] test. A brief survey questionnaire was requested be filled to ascertain the exposure to known risk factors for CA-MRSA carriage. RESULTS: Overall, nasal colonization with CA-MRSA was seen in 34 individuals (18%, 95% confidence interval [CI] =12.5%-23.5%), whereas, CA-MRSA was additionally isolated from the cell phone surface in 12 participants (6.3%, 95% CI =5.6% 6.98%). Nasal colonization prevalence with hospital-acquired [HA] MRSA was seen in 16 individuals (13.8%, 95% confidence interval [CI] =7.5%-20.06%), whereas, HA MRSA was additionally isolated from the cell phone surface in 3 participants (2.6%, 95% CI =1.7-4.54). Antibiotic sensitivity was 100% to linezolid and rifampicin in the CA-MRSA isolates. Antibiotic resistance to vancomycin and clindamycin varied between 9-11 % in the CA-MRSA isolates. Mean MIC for vancomycin amongst CA- and HA-MRSA were 6.3 and 9.3 MUg/ml, whereas for teicoplanin they were 13 and 14 MUg/ml respectively by the E-test. There was no statistically significant correlation between CA-MRSA nasal carriage and the risk factors (P>0.05, Chi-square test). CONCLUSIONS: The prevalence of CA-MRSA in the healthy community hospital visitors was 18 % (95% CI, 12.5% to 23.5%) as compared to 13.8% HA-MRSA in the hospital health-care staff. Despite a significant prevalence of CA-MRSA, these strains were mostly sensitive. RECOMMENDATION: The universal techniques of hand washing, personal hygiene and sanitation are thus warranted. PMID- 26543520 TI - The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-beta Production in Alzheimer's Disease. AB - An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer's disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Abeta) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Abeta overproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Abeta plaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors. PMID- 26543524 TI - Management of Meningitis Caused by Multi Drug-Resistant Acinetobacter Baumannii: Clinical, Microbiological and Pharmacokinetic Results in a Patient Treated with Colistin Methanesulfonate. AB - This paper reports on a 71- year-old Caucasian male who underwent neurosurgery for an oligodendroglioma, followed by a cranial-sinus fistula and cerebrospinal fluid rhinorrhea. The clinical course was complicated due to an extensively drug resistant Acinetobacter baumannii meningitis. The patient was treated with colistin methanesulfonate, intrathecal for 24 days and intravenous for 46 days. In addition, the patient received meropenem and teicoplanin to treat a urinary tract infection and a bacterial aspiration pneumonia. Cerebrospinal fluid trough colistin levels resulted above the MIC of A. baumannii. Colistin cerebrospinal fluid concentration did not increase over the treatment period. Meningitis was cured and A. baumannii eradicated. No side effects from the antimicrobial therapy were observed. In conclusion, this case highlights the issues in treating infections caused by resistant Gram negative bacteria and supports previous findings on the efficacy, pharmacokinetic and tolerability of intravenous and intrathecal colistin treatments. PMID- 26543523 TI - Demographical, Viro-Immunological, Clinical and Therapeutical Characteristics of HIV-Infected Patients in an "Epidemiologically Unexplored" Region of Italy (Calabria Region): the CalabrHIV Cohort. AB - BACKGROUND AND OBJECTIVES: HIV epidemics may differ among epidemiological contexts. We aimed at constructing an HIV clinical cohort whose main epidemiological, clinical and therapeutical characteristics are described (the CalabrHIV cohort, Calabria Region, Southern Italy). METHODS: The CalabrHIV Cohort includes all HIV patients on active follow-up in all infectious disease centers in the Calabria Region as at October 2014. All information was recorded in a common electronic database. Not-infectious co-morbidities (such as cardiovascular diseases, bone fractures, diabetes, renal failure and hypertension) were also studied. RESULTS: 548 patients (68% males; 59% aged <50 years) were included in the CalabrHIV cohort. Major risk factors were: sexual transmission (49%) and intravenous drug use (34%). 39% patients had HCV and/or HBV co-infection. Amongst 404 patients who had a complete clinical history, 34% were AIDS presenters and 49.3% had CD4 count <=350/mm(3) at HIV diagnosis. 83% patients on HAART had undetectable HIV-RNA. Hypertension was the most frequent co-morbidity (21.5%). Multimorbidity was more frequent in >50 years old patients than in <50 years old ones (30% vs. 6%; p<0.0001). Co-morbidity was more frequent in HCV and/or HBV co infected than in HIV mono-infected patients (46.6% vs. 31.7%: p=0.0006). CONCLUSION: This cohort presentation study sheds light, for the first time, on HIV patients' characteristics in the Calabria Region. We showed that HIV-infected patients with chronic hepatitis were affected by concomitant not-infectious co morbidities more than the HIV mono-infected individuals. New HCV treatments are therefore to be implemented in the co-infected population. PMID- 26543525 TI - Chronic Lymphocytic Leukaemia: Census of Patients Treated in Italian Haematology Units. AB - This study was conducted by contacting the population of the Italian haematology units and collecting from 68% of them data concerning the number of patients with chronic lymphocytic leukaemia visited over the previous 12 months, with the aim of obtaining an overview of the treatment of this disease and comparing the results with the prevalence estimates found in literature. The projection obtained (about 17,000 patients visited in the previous 12 months) is probably overestimated because of double-counting of patients who may have been treated at two different facilities during the year, although it is also underestimated since the internal medicine units were not involved. The balance of these two opposite factors is not known. It is important to bear in mind the approximation with which the count was performed in facilities for which no official data were available. Albeit with these limits, the results obtained are in line with some existing prevalence data and make it possible to determine the portion of patients at different Binet stages and in the various age ranges, identifying the corresponding therapeutic treatments. Use of the CIRS scale to classify patients as FIT and UNFIT was seen to be still somewhat limited. PMID- 26543528 TI - Role of Biomarkers as Predictors of Infection and Death in Neutropenic Febrile Patients after Hematopoietic Stem Cell Transplantation. AB - An ideal marker in the neutropenic population after HSCT is the one which positivetes at the onset of fever, or at most up to 24 hours after its onset, the patients at potential risk for infection due to bacterial and fungi and mortality. Several biomarkers have been used in HSCT patients in the last decade. However, it seems that C-RP and Il-6 are the most useful markers to early detected infection and risk for death. PMID- 26543527 TI - Efficacy and Safety of Cladribine: Subcutaneous versus Intravenous Administration in Hairy Cell Leukemia Patients. AB - Cladribine induces durable complete remission (CR) in approximately 85% of hairy cell leukemia (HCL) patients. In Egypt, cladribine is mainly used as IV continuous infusion at a dose of 0.1 mg/kg/day for 7 days and as SC bolus injection at a dose of 0.14 mg/kg/day for 5 days. We aimed to compare the outcome and toxicity between these two regimens. We retrospectively collected data from HCL patients treated at the National Cancer Institute and its affiliated center, Nasser Institute, Cairo, Egypt. Forty-nine patients were identified, 18 treated with the IV regimen (IV group) and 31 with the SC regimen (SC group). Forty-one patients were newly diagnosed. Patient characteristics were balanced across the two groups. The CR rates in the IV and the SC group were 94% and 97%, respectively. The main complications in the IV group and the SC were neutropenia G3-4 (67% vs. 87%), mucositis mainly G1-2 (67% vs 32%) and infections (mainly viral, 78% vs 34%). In the IV group, five patients died, three of progression and infection, one of unknown cause and one of late heart failure. In the SC group, one patient died of disease progression and one of second cancer. After 33.5 months, median follow-up, the 3-year event free survival was 60% and 96%, respectively (p=0.104). The 3-year overall survival was 81% and 100%, respectively (p=0.277). In conclusion, SC cladribine is an excellent alternative to the IV regimen for the treatment of HCL. PMID- 26543526 TI - Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases. AB - Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram-negative (G-) bacteria. The underlying disease is the most important factor in determining the frequency and severity of infections. So, splenectomy for malignant diseases has the major risk of infections. PMID- 26543529 TI - Serum Total Bilirubin, not Cholelithiasis, is Influenced by UGT1A1 Polymorphism, Alpha Thalassemia and beta(s) Haplotype: First Report on Comparison between Arab Indian and African beta(s) Genes. AB - BACKGROUND: We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian beta(S) haplotypes, but sharing the same microgeographical environment and comparable life style factors. METHODS: 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography were routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136), beta(s) haplotypes(n=136), alpha globin gene status (n=105) and UGT1A1 genotypes (n=133) were reviewed from the respective medical records. RESULTS: The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT)7 group as compared to UGT1A1(AT)6 group. Thus, not cholelithiasis but total serum bilirubin was influenced by UGT1A1 polymorphism in this SCA cohort. CONCLUSION: As observed in other population groups, the UGT1A1 (AT)7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with alpha thalassaemia, UGT1A1 polymorphism, or beta(s) haplotypes. PMID- 26543530 TI - Cardiovascular effects of the incretin-based therapy: the good, the bad, or the ugly? PMID- 26543532 TI - Safety, efficacy, and early clinical experience of insulin degludec in Japanese people with diabetes mellitus: A first-year report from Japan. AB - In Japan, insulin therapy is recommended for the treatment of type 2 diabetes mellitus either directly after diet, exercise and lifestyle improvements, or if the target for glycemic control is not achieved with other hypoglycemic agents. Insulin degludec is an ultra-long-acting insulin that was launched in Japan in 2013, having shown good efficacy and safety in its clinical development program. It has now been used in clinical practice for more than 1 year. During this time, clinicians and researchers have identified possible factors that could influence the decision as to which patients might be appropriate for insulin degludec treatment. In the present review, we describe how to initiate and manage insulin degludec therapy in routine clinical practice. We also discuss several important topics related to the use of insulin degludec, including patient selection, dosing, handling of bolus insulin, hypoglycemia and other potential safety considerations. PMID- 26543531 TI - New mechanisms of metformin action: Focusing on mitochondria and the gut. AB - The most well-known mechanism of metformin action, one of the most commonly prescribed antidiabetic drugs, is adenosine monophosphate-activated protein kinase activation; however, recent investigations have shown that adenosine monophosphate-activated protein kinase-independent pathways can explain some of metformin's beneficial metabolic effects as well as undesirable side-effects. Such novel pathways include induction of mitochondrial stress, inhibition of mitochondrial shuttles, alteration of intestinal microbiota, suppression of glucagon signaling, activation of autophagy, attenuation of inflammasome activation, induction of incretin receptors and reduction of terminal endoplasmic reticulum stress. Together, these studies have broadened our understanding of the mechanisms of antidiabetic agents as well as the pathogenic mechanism of diabetes itself. The results of such investigations might help to identify new target molecules and pathways for treatment of diabetes and metabolic syndrome, and could also have broad implications in diseases other than diabetes. Accordingly, new antidiabetic drugs with better efficacy and fewer adverse effects will likely result from these studies. PMID- 26543533 TI - Pharmacological interventions for painful diabetic neuropathy: Comparative analysis using network meta-analysis. PMID- 26543534 TI - Sarcopenia and diabetes: Hyperglycemia is a risk factor for age-associated muscle mass and functional reduction. PMID- 26543535 TI - Peptide modulators of alpha-glucosidase. AB - AIMS/INTRODUCTION: Acute glucose fluctuations during the postprandial period pose great risk for cardiovascular complications and thus represent an important therapeutic approach in type 2 diabetes. In the present study, screening of peptide libraries was used to select peptides with an affinity towards mammalian intestinal alpha-glucosidase as potential leads in antidiabetic agent development. MATERIALS AND METHODS: Three phage-displayed peptide libraries were used in independent selections with different elution strategies to isolate target-binding peptides. Selected peptides displayed on phage were tested to compete for an enzyme-binding site with known competitive inhibitors, acarbose and voglibose. The four best performing peptides were synthesized. Their binding to the mammalian alpha-glucosidase and their effect on enzyme activity were evaluated. RESULTS: Two linear and two cyclic heptapeptides with high affinity towards intestinal alpha-glucosidase were selected. Phage-displayed as well as synthetic peptides bind into or to the vicinity of the active site on the enzyme. Both cyclic peptides inhibited enzyme activity, whereas both linear peptides increased enzyme activity. CONCLUSIONS: Although natural substrates of glycosidase are polysaccharides, in the present study we successfully isolated novel peptide modulators of alpha-glucosidase. Modulatory activity of selected peptides could be further optimized through peptidomimetic design. They represent promising leads for development of efficient alpha-glucosidase inhibitors. PMID- 26543536 TI - Detection of CAPN10 copy number variation in Thai patients with type 2 diabetes by denaturing high performance liquid chromatography and real-time quantitative polymerase chain reaction. AB - AIMS/INTRODUCTION: A combination of multiple genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Copy number variations (CNVs) are associated with complex human diseases. However, CNVs can cause genotype deviation from the Hardy-Weinberg equilibrium (HWE). A genetic case-control association study in 216 Thai diabetic patients and 192 non-diabetic controls found that, after excluding genotyping errors, genotype distribution of calpain 10 (CAPN10) SNP44 (rs2975760) deviated from HWE. Here, we aimed to detect CNV within the CAPN10 SNP44 region. MATERIALS AND METHODS: CNV within the CAPN10 SNP44 region was detected using denaturing high-performance liquid chromatography, and the results confirmed by real-time quantitative polymerase chain reaction with SYBR Green I. RESULTS: Both methods successfully identified CNV in the CAPN10 SNP44 region, obtaining concordant results. Correction of genotype calling based on the status of identified CNVs showed that the CAPN10 SNP44 genotype is in good agreement with HWE (P > 0.05). However, no association between CNV genotypes and risk of type 2 diabetes was observed. CONCLUSIONS: Identified CNVs for CAPN10 SNP44 genotypes lead to deviation from HWE. Furthermore, both denaturing high-performance liquid chromatography and real-time quantitative polymerase chain reaction are useful for detecting CNVs. PMID- 26543537 TI - Lack of predictive power of plasma lipids or lipoproteins for gestational diabetes mellitus in Japanese women. AB - AIMS/INTRODUCTION: To determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20-28 weeks of gestation who underwent a glucose challenge test (GCT). MATERIALS AND METHODS: A total of 1,161 Japanese women at 20-28 weeks of gestation underwent a GCT. Participants with a positive test (GCT[+]) underwent a subsequent oral glucose tolerance test. Clinical and biochemical parameters were determined and quantification of apolipoproteins (Apo), including ApoB, ApoB48, ApoA-I and ApoC-III, was carried out. RESULTS: The prevalence of GCT(+; with a 130 mg/dL glucose cut-off) and GDM was 20% and 4%, respectively. There was a trend for increased triglycerides and ApoC-III in GDM(+) participants. However, the difference in plasma triglycerides, ApoC-III or ApoB48 did not reach statistical significance between GDM(+) and GDM( ) women. Values of 1-h glucose (P < 0.001) and fasting glucose (P = 0.002) were significant risk factors for GDM. CONCLUSIONS: Prediction of GDM using only the ApoC-III value is not easy, although triglycerides and ApoC-III were higher in the GDM(+) group. The present findings show no significant difference in plasma lipid levels between women diagnosed with GDM and those with normal glucose tolerance. PMID- 26543538 TI - Predictability of 1-h postload plasma glucose concentration: A 10-year retrospective cohort study. AB - AIMS/INTRODUCTION: Elevated 1-h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut-off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long-term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis. MATERIALS AND METHODS: A total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, were investigated. Follow-up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis. RESULTS: The areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut-off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG >=8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223-45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima-media thickness in the subjects with 1hPG >=8.85 mmol/L tended to be higher compared with those <8.85 mmol/L. CONCLUSIONS: 1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut-off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG >=8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis. PMID- 26543539 TI - Strength training and risk of type 2 diabetes in a Japanese working population: A cohort study. AB - AIMS/INTRODUCTION: Muscle strength training has been suggested to improve glucose metabolism; however, epidemiological evidence regarding strength training's effects on diabetes risk is scarce. We prospectively examined the association between strength training and the risk of type 2 diabetes in Japanese men and women. MATERIALS AND METHODS: The sample included health checkups on 26,630 Japanese male and female workers aged 30-64 years without diabetes at baseline. Weekly time spent on strength training was elicited using a self-reported questionnaire. Type 2 diabetes was diagnosed based on hemoglobin A1c, fasting glucose, random plasma glucose and self-report in an annual health checkup. Hazard ratio (HR) and its 95% confidence interval (CI) for incident diabetes was estimated using a Cox proportional hazards model. RESULTS: During a mean follow up of 5.2 years with 139,748 person-years, 1,770 individuals developed diabetes. Age- and sex-adjusted HR for diabetes was 0.58 (95% CI 0.42-0.79) in those who engaged in strength training compared with those who engaged in no strength training. After further adjusting for potential confounders, the corresponding HR was 0.66 (95% CI 0.48-0.90). Additional adjustment for body mass index did not materially change the result; the HR was 0.70 (95% CI 0.51-0.96). The association was more pronounced in individuals aged 50 years or older than those aged <50 years, although the difference in the association by age was not significant. CONCLUSIONS: These results suggest that engagement in strength training could help to reduce the risk of type 2 diabetes in a Japanese working population. PMID- 26543540 TI - Adherence to self-care behavior and glycemic effects using structured education. AB - AIMS/INTRODUCTION: The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation MapTM (CMTM) vs usual care in a university-based hospital primary care clinic. MATERIALS AND METHODS: This was a randomized, pragmatic clinical trial. Patients with type 2 diabetes were randomly assigned to structured education or usual care groups. The primary outcome was the difference in the mean change of glycated hemoglobin (HbA1c) from baseline to 12 months. Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes. RESULTS: A total of 245 patients were randomly assigned to two groups (CMTM group n = 121; usual care group, n = 116). The absolute reduction of HbA1c was significantly greater in the CMTM group at 3 and 6 months (Delta = -0.59% and Delta = -1.13%, P < 0.01), but the difference was no longer statistically significant at 9 and 12 months (Delta = -0.43% and Delta = 0.49%), based on an intention-to-treat analysis. A per-protocol analysis showed the significant change was maintained at 12 months (Delta = -0.67%). In the intervention group, greater percentages of patients achieved their American Association of Diabetes Educators Self-Care BehavioursTM framework (AADE7) behavioral goals at 3 months, in particular being active, problem-solving, reducing risk and health coping. CONCLUSIONS: In type 2 diabetic patients with suboptimally controlled glucose, there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CMTM education program compared with outcomes achieved in patients receiving usual care. PMID- 26543541 TI - Simple risk score to detect rural Asian Indian (Bangladeshi) adults at high risk for type 2 diabetes. AB - AIMS/INTRODUCTION: To develop and evaluate a simple, non-invasive, diabetes risk score for detecting individuals at high risk for type 2 diabetes in rural Bangladesh. MATERIALS AND METHODS: Data from 2,293 randomly selected individuals aged >=20 years from a cross-sectional study in a rural community of Bangladesh (2009 Chandra Rural Study) was used for model development. The validity of the model was assessed in another rural cross-sectional study (2009 Thakurgaon Rural Study). The logistic regression model used included age, sex, body mass index, waist-to-hip ratio and hypertension status to predict individuals who were at high risk for type 2 diabetes. RESULTS: On applying the developed model to both cohorts, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval 0.68-0.72) for the Chandra cohort and 0.71 (95% confidence interval 0.68-0.74) for the Thakurgaon cohort. The risk score of >9 was shown to have the optimal cut-point to detect diabetes. This score had a sensitivity of 62.4 and 75.7%, and specificity of 67.4 and 61.6% in the two cohorts, respectively. This risk score was shown to have improved sensitivity and specificity to detect type 2 diabetes cases compared with the Thai, Indian, Omani, UK, Dutch, Portuguese and Pakistani diabetes risk scores. CONCLUSIONS: This simple, non-invasive risk score can be used to detect individuals at high risk for type 2 diabetes in rural Bangladesh. Subjects with a score of 9 or above (out of 15) should undergo an oral glucose tolerance test for definitive diagnosis of diabetes. PMID- 26543542 TI - Carbohydrate intake is associated with time spent in the euglycemic range in patients with type 1 diabetes. AB - AIMS/INTRODUCTION: Greater glycemic variability and lack of predictability are important issues for patients with type 1 diabetes. Dietary factors are one of the contributors to this variability, but how closely diet is linked to glycemic fluctuation on a daily basis has not been investigated. We examined the association between carbohydrate intake and glycemic excursion in outpatients. MATERIALS AND METHODS: A total of 33 patients with type 1 diabetes were included in the analyses (age 44.5 +/- 14.7 years, diabetes duration 15.1 +/- 8.3 years, 64% female, 30% using insulin pump, glycated hemoglobin 8.1 +/- 1.3%). Time spent in euglycemia (70-180 mg/dL), hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) of consecutive 48-h periods of continuous glucose monitoring data were collected together with simultaneous records of dietary intake, insulin dose and physical activity. Correlation analyses and multiple regression analyses were used to evaluate the contribution of carbohydrate intake to time spent in the target glycemic range. RESULTS: In multiple regression analyses, carbohydrate intake (beta = 0.53, P = 0.001), basal insulin dose per kg per day (beta = -0.31, P = 0.034) and diabetes duration (beta = 0.30, P = 0.042) were independent predictors of time spent in euglycemia. Carbohydrate intake (beta = -0.51, P = 0.001) and insulin pump use (beta = -0.34, P = 0.024) were independent predictors of time spent in hyperglycemia. Insulin pump use (beta = 0.52, P < 0.001) and bolus insulin dose per kg per day (beta = 0.46, P = 0.001) were independent predictors of time spent in hypoglycemia. CONCLUSIONS: Carbohydrate intake is associated with time spent in euglycemia in patients with type 1 diabetes. PMID- 26543543 TI - The relationship between the frequency of self-monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections. AB - AIMS/INTRODUCTION: We investigated the relationship between the frequency of self monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software. MATERIALS AND METHODS: We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNETTM SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients' hemoglobin A1c (HbA1c) levels was analyzed using the chi(2) test and linear regression analysis was carried out to clarify their relationship. RESULTS: The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of >=3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72-28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62-2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = -0.24 * SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = -2.61 * SMBG frequency {times/day} + 70.5], [r = -0.384, P = 0.012]), but not in the MDI group. CONCLUSIONS: A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c >=8%) in type 1 diabetes mellitus patients on CSII. PMID- 26543544 TI - Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: A multinational, 24-week, randomized, clinical trial. AB - AIMS/INTRODUCTION: Asian patients represent a large portion of the global population with type 2 diabetes mellitus, but are underrepresented in trials of glucose-lowering therapies. The present randomized, phase III, placebo controlled, double-blind, 24-week study evaluated the dipeptidyl peptidase-4 inhibitor, linagliptin, as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus. MATERIALS AND METHODS: Patients who were treatment naive or had been treated with one oral antidiabetes drug were randomized to either linagliptin 5 mg daily or a placebo after washout. The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks. RESULTS: A total of 300 Asian (87% Chinese) patients with type 2 diabetes mellitus were randomized to linagliptin or placebo at a 2:1 ratio. After 24 weeks of treatment, adjusted mean (standard error) glycated hemoglobin decreased by a placebo-corrected -0.50 +/- 0.11 (P < 0.0001). In patients with baseline glycated hemoglobin >=8.5%, the placebo-corrected decrease in glycated hemoglobin was 0.91 +/- 0.20% (P < 0.0001). Adverse events occurred in 28.0 and 28.3% of linagliptin and placebo patients, respectively, but few were drug-related (3.0 and 2.0%, respectively). Hypoglycemia was reported by one linagliptin patient and no placebo patients. Treatment with linagliptin was weight neutral. CONCLUSIONS: In Asian patients with inadequately controlled type 2 diabetes mellitus, linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks. PMID- 26543545 TI - Effects of a sodium glucose co-transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring. AB - AIMS/INTRODUCTION: To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes. MATERIALS AND METHODS: We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3 hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls. RESULTS: Continuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 +/- 54 mg/dL to 141 +/- 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of beta-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 +/ 0.5 vs 0.5 +/- 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively. CONCLUSIONS: The ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss. PMID- 26543546 TI - Insulin combined with Chinese medicine improves glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus. AB - INTRODUCTION/AIMS: Insufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type 2 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen-Qi-Formula (SQF), a well-known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type 2 diabetes mellitus, and what mechanisms were possibly involved in the treatment. MATERIALS AND METHODS: A total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12-week treatment, the fasting blood glucose, postprandial blood glucose, beta-cell function, insulin resistance and blood lipids were measured. RESULTS: The 12 weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but beta-cell function and insulin resistance were obviously improved. Furthermore, 12 weeks of treatment with SQF and insulin improved the levels of glucagon-like peptide-1, oxidative stress, blood lipids, coagulation function and bodyweight. CONCLUSION: The results from our study showed that the combination therapy of SQF and insulin significantly improved the clinical outcome of type 2 diabetes mellitus compared with insulin monotherapy. The mechanism of improvement was possibly involved in the multiple pathways. PMID- 26543547 TI - Current status of glucose, blood pressure and lipid management in type 2 diabetes clinic attendees in Isfahan, Iran. AB - AIMS/INTRODUCTION: To estimate the prevalence of meeting American Diabetes Association clinical practice recommendations for hemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) among Iranian type 2 diabetes clinic attendees, and to identify the factors associated with therapeutic target achievement. MATERIALS AND METHODS: A total of 2,640 patients with type 2 diabetes (944 men and 1,696 women) from Isfahan Endocrine and Metabolism Research Center outpatient clinics, Iran, were examined. The main outcome measures were HbA1c, BP and LDLC, in accordance with the American Diabetes Association recommendations. The mean (standard deviation) age of participants was 49.6 years (9.3 years) with a mean (standard deviation) duration of diabetes of 5.0 years (4.9 years) at initial registration. RESULTS: The percentages of patients who had HbA1c <7%, BP <140/90 mmHg and LDLC <100 mg/dL was 37.4% (95% confidence interval [CI] 35.6-39.3), 35.3% (95% CI 33.5-37.3) and 48.9% (95% CI 47.0-50.8), respectively. The proportion of patients meeting all three goals was 7.7% (95% CI 6.7-8.8). Lower BP, cholesterol level and higher education at registration, and higher follow up but lower number of follow-up visits affected achievement of all three goals. CONCLUSIONS: The present study highlights that a substantial proportion of Iranian type 2 diabetes clinic attendees did not meet the American Diabetes Association clinical practice recommendations, and shows the difficult challenges physicians face when treating patients with type 2 diabetes. PMID- 26543548 TI - Type 1 diabetes patients have lower strength in femoral bone determined by quantitative computed tomography: A cross-sectional study. AB - AIMS/INTRODUCTION: Previous studies have reported osteoporosis measured by dual energy X-ray absorptiometry in younger patients with type 1 diabetes. Limitations of 2-D imaging, however, limit the precision of dual-energy X-ray absorptiometry for the measurement of bone mineral density and bone strength. MATERIALS AND METHODS: Three-dimensional quantitative computed tomography was used to calculate volumetric-bone mineral density (vBMD) and strength in femoral bone subfractions. A total of 17 male type 1 diabetes patients and 18 sex-matched healthy controls aged from 18 to 49 years were investigated in the present cross-sectional study. Patients with overt nephropathy were excluded. RESULTS: Type 1 diabetes patients had significantly lower cortical vBMD in the femoral neck, and significantly lower total vBMD, cortical thickness and cortical cross-sectional area (cortical CSA) in the intertrochanter. Bone strength estimated by the buckling ratio (an index of cortical instability) of the intertrochanter was significantly higher in type 1 diabetes patients. The following serum bone markers were comparable between the two groups: bone-specific alkaline phosphatase, N-terminal propeptide of type 1 procollagen, osteocalcin, pentosidine and homocysteine. Serum insulin like growth factor-1 values were significantly lower in the type 1 diabetes patients than in controls. Serum insulin-like growth factor-1values were positively correlated with serum bone formation markers, and the total vBMD of the femoral neck and lumbar spine in type 1 diabetes patients. CONCLUSIONS: The present study is the first investigation by quantitative computed tomography measurement to show cortical instability and lower vBMD in the intertrochanter of young and middle-aged type 1 diabetes patients. Low insulin-like growth factor-1 might be a causative factor for osteoporosis in type 1 diabetes. PMID- 26543549 TI - Efficacy of oral glucocorticoid and cyclosporine in a case of rituximab refractory type B insulin resistance syndrome. AB - We describe a case of type B insulin resistance syndrome associated with systemic lupus erythematosus (SLE) that was refractory to rituximab and successfully treated with a combination of oral glucocorticoids and cyclosporine. Prior to treatment, insulin resistance was severe, and application of a hyperinsulinemic euglycemic clamp was not possible despite the continuous intravenous infusion of insulin at a maximum rate of 9.0 mU/kg/min. The addition of cyclosporine to oral glucocorticoid therapy resulted in remission of insulin resistance. The combination of oral prednisolone and cyclosporine might be effective in treating type B insulin resistance syndrome, particularly in rituximab-resistant cases. However, nephrotoxicity is a particular concern for patients receiving long-term cyclosporine therapy. PMID- 26543550 TI - Bending of a vertical cannula without alarm during insulin pump therapy as a cause of unexpected hyperglycemia: A Japanese issue? PMID- 26543552 TI - Magnesium sulfate has sex-specific, dose-dependent vasodilator effects on preterm placental vessels. AB - BACKGROUND: Women at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child's risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain. METHODS: The aim of this study was to examine MgSO4 action on vascular tone in male and female human placental vessels from term and preterm deliveries. Vessels were obtained from placental biopsy following birth at term (37-41 weeks) or preterm gestation (<36 weeks of gestation). The vessels were mounted on a pressure myograph, pre-constricted with synthetic endoperoxide prostaglandin PGH2 (U46619) (0.1-100 MUmol/l), and percentage of relaxation was calculated following incubation with bradykinin. Experiments were carried out in the presence of MgSO4 (0.2 mmol/l), NPsi-nitro-L arginine methyl ester (L-NAME) (0.1 mmol/l), indomethacin (10 MUmol/l), Ca(2+) activated K(+) channel blocker TRAM-34 (1 MUM) and apamin (3 MUM) to assess mechanisms of vascular function. Vascular [calcium ions (Ca(2+))] was analysed using a colorimetric calcium assay. RESULTS: Vasodilation in vessels from preterm males was significantly blunted in the presence of MgSO4 when compared to preterm female and term male and female vessels. Overall, MgSO4 was observed to differentially modulate placental vascular tone and vascular calcium concentrations in a sex-specific manner. CONCLUSIONS: As MgSO4 regulates human placental blood flow via specific pathways, foetal sex-specific MgSO4 treatment regimes may be necessary. In an era of increasing awareness of individualised medicine, sex-specific effects may be of importance when developing strategies to optimise care in high-risk patients. PMID- 26543554 TI - 1-Octen-3-ol - the attractant that repels. AB - Since the discovery in the early 1980s that 1-octen-3-ol, isolated from oxen breath, attracts tsetse fly, there has been growing interest in exploring the use of this semiochemical as a possible generic lure for trapping host-seeking mosquitoes. Intriguingly, traps baited with 1-octen-3-ol captured significantly more females of the malaria mosquito, Anopheles gambiae, and the yellow fever mosquito, Aedes aegypti, than control traps, but failed to attract the southern house mosquito, Culex quinquefasciatus. Additionally, it has been demonstrated that this attractant is detected with enantioselective odorant receptors (ORs) expressed only in maxillary palps. On the basis of indoor behavioral assays it has even been suggested that 1-octen-3-ol might be a repellent to the southern house mosquito. Our approach was two-prong, i.e., to isolate 1-octen-3-ol sensitive ORs expressed in maxillary palps and antennae of southern house female mosquito, and test the hypothesis that this semiochemical is a repellent. An OR with high transcript levels in maxillary palps, CquiOR118b, showed remarkable selectivity towards ( R)-1-octen-3-ol, whereas an OR expressed in antennae, CquiOR114b, showed higher preference for ( S)-1-octen-3-ol than its antipode. Repellency by a surface landing and feeding assay showed that not only racemic, but enantiopure ( R)- and ( S)-1-octen-3-ol are repellents at 1% dose thus suggesting the occurrence of other ( S)-1-octen-3-ol-sensitive OR(s). Female mosquitoes with ablated maxillary palps were repelled by 1-octen-3-ol, which implies that in addition to OR(s) in the maxillary palps, antennal OR(s) are essential for repellency activity. PMID- 26543555 TI - Seeing and believing: recent advances in imaging cell-cell interactions. AB - Advances in cell and developmental biology have often been closely linked to advances in our ability to visualize structure and function at many length and time scales. In this review, we discuss how new imaging technologies and new reagents have provided novel insights into the biology of cadherin-based cell cell junctions. We focus on three developments: the application of super resolution optical technologies to characterize the nanoscale organization of cadherins at cell-cell contacts, new approaches to interrogate the mechanical forces that act upon junctions, and advances in electron microscopy which have the potential to transform our understanding of cell-cell junctions. PMID- 26543553 TI - The accuracy of diagnostic ultrasound imaging for musculoskeletal soft tissue pathology of the extremities: a comprehensive review of the literature. AB - Musculoskeletal diagnostic ultrasound imaging (MSK-DUSI) has been growing outside the traditional radiology speciality. Increased use of this technology has been reported in several healthcare settings, however an apparent gap in the knowledge of the accuracy of this diagnostic technology indicated a review was warranted. We undertook a structured review of the literature to assess the accuracy of MSK DUSI for the diagnosis of musculoskeletal soft tissue pathology of the extremities. An electronic search of the National Library of Medicine's PubMed database (1972 to mid-2014) was conducted. All relevant systematic reviews of diagnostic studies, all diagnostic studies published after the date of the latest systematic reviews and relevant diagnostic studies outside the scope the systematic reviews that directly compared the accuracy of MSK-DUSI (the index test) to an appropriate reference standard for the target condition were included. A fundamental appraisal of the methodological quality of studies was completed. The individual sensitivity, specificity and likelihood ratio data were extracted and entered into diagnostic accuracy tables. A total of 207 individual studies were included. The results show that MSK-DUSI has acceptable diagnostic accuracy for a wide spectrum of musculoskeletal conditions of the extremities. However, there is a lack of high quality prospective experimental studies in this area and as such clinicians should interpret the results with some caution due to the potential for overestimation of diagnostic accuracy. PMID- 26543557 TI - The effect of increased atmospheric temperature and CO2 concentration during crop growth on the chemical composition and in vitro rumen fermentation characteristics of wheat straw. AB - This experiment was conducted to investigate the effects of increased atmospheric temperature and CO2 concentration during crop growth on the chemical composition and in vitro rumen fermentation characteristics of wheat straw. The field experiment was carried out from November 2012 to June 2013 at Changshu (31 degrees 32'93"N, 120 degrees 41'88"E) agro-ecological experimental station. A total of three treatments were set. The concentration of CO2 was increased to 500 MUmol/mol in the first treatment (CO2 group). The temperature was increased by 2 degrees C in the second treatment (TEM group) and the concentration of CO2 and temperature were both increased in the third treatment (CO2 + TEM group). The mean temperature and concentration of CO2 in control group were 10.5 degrees C and 413 MUmol/mol. At harvesting, the wheat straws were collected and analyzed for chemical composition and in vitro digestibility. Results showed that dry matter was significantly increased in all three treatments. Ether extracts and neutral detergent fiber were significantly increased in TEM and CO2 + TEM groups. Crude protein was significantly decreased in CO2 + TEM group. In vitro digestibility analysis of wheat straw revealed that gas production was significantly decreased in CO2 and CO2 + TEM groups. Methane production was significantly decreased in TEM and CO2 + TEM groups. Ammonia nitrogen and microbial crude protein were significantly decreased in all three treatments. Total volatile fatty acids were significantly decreased in CO2 and CO2 + TEM groups. In conclusion, the chemical composition of the wheat straw was affected by temperature and CO2 and the in vitro digestibility of wheat straw was reduced, especially in the combined treatment of temperature and CO2. PMID- 26543556 TI - Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2. AB - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes account for 20-25 % of inherited breast cancers and about 10 % of all breast cancer cases. Detection of BRCA mutation carriers can lead to therapeutic interventions such as mastectomy, oophorectomy, hormonal prevention therapy, improved screening, and targeted therapies such as PARP-inhibition. We estimate that African Americans and Hispanics are 4-5 times less likely to receive BRCA screening, despite having similar mutation frequencies as non-Jewish Caucasians, who have higher breast cancer mortality. To begin addressing this health disparity, we initiated a nationwide trial of BRCA testing of Latin American women with breast cancer. Patients were recruited through community organizations, clinics, public events, and by mail and Internet. Subjects completed the consent process and questionnaire, and provided a saliva sample by mail or in person. DNA from 120 subjects was used to sequence the entirety of BRCA1 and BRCA2 coding regions and splice sites, and validate pathogenic mutations, with a total material cost of $85/subject. Subjects ranged in age from 23 to 81 years (mean age, 51 years), 6 % had bilateral disease, 57 % were ER/PR+, 23 % HER2+, and 17 % had triple-negative disease. RESULTS: A total of seven different predicted deleterious mutations were identified, one newly described and the rest rare. In addition, four variants of unknown effect were found. CONCLUSIONS: Application of this strategy on a larger scale could lead to improved cancer care of minority and underserved populations. PMID- 26543558 TI - A retrospective study of the impact of DSM-5 on the diagnosis of eating disorders in Victoria, Australia. AB - BACKGROUND: This study compares the DSM-IV and DSM-5 diagnostic criteria for eating disorders. DSM-IV resulted in a large number of patients being diagnosed with Eating Disorder Not Otherwise Specified (EDNOS). In DSM-5 the residual category is renamed Other Specified Feeding and Eating Disorders (OSFED) and Unspecified Eating Disorders (UFED) however the diagnostic criteria for the residual category in each of the diagnostic systems remains the same. This study aims to evaluate the changes in percentages of patients in a residual DSM-IV category compared to a residual DSM-5 category by retrospectively applying DSM-5 criteria to the clinical records of a patient population in a clinical setting. It also aims to compare the psychopathology between the EDNOS and OSFED/UFED groups. METHODS: 285 participants were recruited from a specialised eating disorder clinic in Australia over a 5-year period from 2009 until 2014. The clinical records of patients with diagnoses of anorexia nervosa (AN), bulimia nervosa (BN) and EDNOS were retrospectively assessed using the DSM-5 criteria. All patients who had attended the clinic and received an eating disorder diagnosis during this period were included in the study. No patients were diagnosed with binge eating disorder during the study period. This is surprising given the prevalence of binge eating disorder in the community. It is possible that individuals with binge eating disorder were not referred to the clinic following the initial referral and assessment due to the lack of binge eating specific interventions available. The referral process may also have been skewed towards AN, BN and EDNOS due to a perception by referring parties that binge eating disorder was a 'milder' condition that did not require specialist intervention. Information in the clinical records included structured clinical interviews, and self-rating scales of eating disorder and other psychiatric symptoms and a longitudinal narrative of patient performance and attitude during observed meals. RESULTS: We observed a 23.5% reduction in the diagnosis of OSFED/UFED with the implementation of DSM-5 compared to EDNOS with DSM-IV. The removal of Criterion D, amenorrhoea, was the leading cause for transition from EDNOS to AN. CONCLUSIONS: DSM-5 has reduced the reliance on EDNOS. However this study was unable to examine the reliability of the new diagnostic criteria or the impact of DSM-5 on binge eating disorder. PMID- 26543559 TI - A striking response of plasmablastic lymphoma of the oral cavity to bortezomib: a case report. AB - BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non Hodgkin diffuse large B-cell lymphoma originally with a predilection to the oral cavity of patients infected with HIV. However, PBL of extraoral sites possesses clinicopathological characteristics distinct from oral PBL. Recently, therapeutic approaches using a proteasome inhibitor bortezomib to PBL of extraoral sites have been reported. We present a PBL patient with a bulky tumor of the oral cavity, who dramatically responded to bortezomib. CASE PRESENTATION: The patient was a 58 year-old Japanese male, who presented with a rapidly progressive history of a swelling on his left cheek and restricted mouth opening. He did not have a history or evidence of immunosuppression including HIV infection. A computed tomography demonstrated a bulky tumor in the oral cavity without enlarged lymph nodes. The tumor showed the proliferation of large lymphoid cells with centroblastic morphology, which were positive for CD138, CD38, CD56 and MUM-1, and negative for CD20, CD79a, BCL-6 and HHV8. The Ki-67 proliferation index was almost 100 %. Neither osteolytic lesions nor M-protein was observed. One week after the initiation of bortezomib, a marked regression of the oral tumor was obtained. CONCLUSIONS: Thus, our case demonstrated the effectiveness of bortezomib on PBL of the oral cavity as well as the extraoral sites. PMID- 26543560 TI - 17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development. AB - Combined17alpha-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Hypertension and hypokalemia are essential presenting features. We report an Arab family with four affected XX siblings. The eldest presented with abdominal pain and was diagnosed with a retroperitoneal malignant mixed germ cell tumour. She was hypertensive and hypogonadal. One sibling presented with headache due to hypertension while the other two siblings were diagnosed with hypertension on a routine school check. A homozygous R96Q missense mutation in P450c17 was detected in the index case who had primary amenorrhea and lack of secondary sexual characters at 17 years. The middle two siblings were identical twins and had no secondary sexual characters at the age of 14. All siblings had hypokalemia, very low level of adrenal androgens, high ACTH and high levels of aldosterone substrates. Treatment was commenced with steroid replacement and puberty induction with estradiol. The index case had surgical tumor resection and chemotherapy. All siblings required antihypertensive treatment and the oldest remained on two antihypertensive medications 12 years after diagnosis. Her breast development remained poor despite adequate hormonal replacement. Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare condition but might be underdiagnosed. It should be considered in young patients presenting with hypertension, particularly if there is a family history of consanguinity and with more than one affected sibling. Antihypertensive medication might continue to be required despite adequate steroid replacement. Breast development may remain poor in mutations causing complete form of the disease. LEARNING POINTS: Endocrine hypertension due to rarer forms of CAH should be considered in children and adolescents, particularly if more than one sibling is affected and in the presence of consanguinity.17alpha-hydroxylase/17,20-lyase deficiency is a rare form of CAH but might be underdiagnosed.Blood pressure measurement should be carried out in all females presenting with hypogonadism.Anti-hypertensive medications might be required despite adequate steroid replacement.Initial presenting features might vary within affected members of the same family.Adverse breast development might be seen in the complete enzyme deficiency forms of the disease. PMID- 26543561 TI - Comparison of Binax NOW urine antigen test and pneumococcal DNA assay using qPCR before and after nasopharyngeal swabbing in healthy Malawian children. AB - Diagnosis of invasive pneumococcal disease is challenging. We compared Binax NOW pneumococcal urinary antigen test with blood pneumococcal PCR in healthy Malawian children with and without pneumococcal carriage, and we found a high false positive rate with Binax NOW. Blood pneumococcal PCR positivity was 66/88 (75%) compared to 5/27 (18%) when nasopharyngeal swabbing was performed first compared to after blood sampling for pneumococcal blood PCR. We speculate that nasopharyngeal swabbing may be causing a breach of mucosal integrity, leading to invasion into the bloodstream. These findings need to be confirmed with autolysin based PCR assays. PMID- 26543562 TI - Enterococcus hirae, an unusual pathogen in humans causing urinary tract infection in a patient with benign prostatic hyperplasia: first case report in Algeria. AB - Enterococcus hirae is a zoonotic pathogen rarely isolated from human infections. This case is the first description of E. hirae causing urinary tract infection in a diabetic man with benign prostatic hyperplasia from Algeria. The clinical isolate was identified by MALDI-TOF MS and displayed a multisensitivity antibiotic profile. PMID- 26543401 TI - Search for metastable heavy charged particles with large ionisation energy loss in pp collisions at [Formula: see text] TeV using the ATLAS experiment. AB - Many extensions of the Standard Model predict the existence of charged heavy long lived particles, such as R-hadrons or charginos. These particles, if produced at the Large Hadron Collider, should be moving non-relativistically and are therefore identifiable through the measurement of an anomalously large specific energy loss in the ATLAS pixel detector. Measuring heavy long-lived particles through their track parameters in the vicinity of the interaction vertex provides sensitivity to metastable particles with lifetimes from 0.6 ns to 30 ns. A search for such particles with the ATLAS detector at the Large Hadron Collider is presented, based on a data sample corresponding to an integrated luminosity of [Formula: see text] fb[Formula: see text] of pp collisions at [Formula: see text] TeV. No significant deviation from the Standard Model background expectation is observed, and lifetime-dependent upper limits on R-hadrons and chargino production are set. Gluino R-hadrons with 10 ns lifetime and masses up to 1185 GeV are excluded at 95 [Formula: see text] confidence level, and so are charginos with 15 ns lifetime and masses up to 482 GeV. PMID- 26543563 TI - Unusual staphylococcal toxic shock syndrome presenting as a scarlet-like fever. AB - Diagnosis of nonmenstrual staphylococcal toxic shock syndrome (TSS) is often challenging. A female medical colleague had a rare entity, a staphylococcal pharyngitis complicated by TSS. The diagnosis was confirmed by isolation of tst positive Staphylococcus aureus in throat culture and by identification of a specific Vbeta2 expansion pattern of her T lymphocytes. Recent improvements in microbiology can be of great help for the diagnosis of nonmenstrual TSS. PMID- 26543568 TI - Kin selection and polygyny: can relatedness lower the polygyny threshold? AB - Resource polygyny incurs costs of having to share breeding resources for female breeders. When breeding with a relative, however, such costs may be lessened by indirect fitness benefits through kin selection, while benefits from mutualistic behaviour, such as communal defence, may increase. If so, females should be less resistant to sharing a territory with a related female than with a non-related one. We investigated whether kin selection may lower the threshold of breeding polygynously, predicting a closer relatedness between polygynous females breeding on the same territory than between females breeding on different territories. Northern lapwings, Vanellus vanellus, are suitable for testing this hypothesis as they are commonly polygynous, both sexes take part in nest defence, and the efficiency of nest defence increases with the number of defenders. Using an index of relatedness derived from DNA fingerprinting, we found that female lapwings that shared polygynous dyads were on average twice as closely related as were random females. Furthermore, relatedness did not correlate with distance between breeders, indicating that our findings cannot be explained by natal philopatry alone. Our results suggest that the polygyny threshold in lapwings may be lowered by inclusive fitness advantages of kin selection. PMID- 26543565 TI - Long-term follow-up and suboptimal treatment rates of treatment-eligible chronic hepatitis B patients in diverse practice settings: a gap in linkage to care. AB - BACKGROUND AND AIMS: Despite available effective therapies, only a minority of patients with chronic hepatitis B (CHB) receive treatment. Our goal is to study treatment rates and time to treatment initiation in patients who meet treatment criteria on long-term follow-up. METHODS: We performed a retrospective cohort study of 608 consecutive treatment-eligible patients with CHB (by 2008 US Panel or 2009 American Association for the Study of Liver Disease (AASLD) criteria) at a US community gastroenterology clinic and a university liver clinic between 2007 and 2011. Patients were observed until they started treatment or last follow-up if untreated. RESULTS: Mean age was 44 and most were Asian (96%) with community patients being younger and having lower alanine aminotransferase (ALT) levels. A total of 62% started treatment, and 38% remained untreated after median follow-up of 17 months (IQR=1-40 months). Overall, treatment rate was significantly higher at university liver clinic than in the community (66.7% vs 59.9%, p=0.01). In multivariate analysis, older age (HR 1.02, p=0.002), male gender (HR 1.37, p=0.02), and baseline ALT >45 U/L for males and >29 U/L for females (HR 2.24, p<0.0001) were significant predictors of treatment initiation, but not practice setting. CONCLUSIONS: Approximately 40% of treatment-eligible patients still have not started treatment on longer follow-up. Treatment rates were higher at university clinics, but practice setting was not a predictor for treatment, but older age, male gender, and higher ALT levels were. Further studies are needed to determine the barriers for treatment initiation and to improve treatment rates in treatment-eligible patients. PMID- 26543569 TI - The development of a segment-based musculoskeletal model of the lower limb: introducing FreeBody. AB - Traditional approaches to the biomechanical analysis of movement are joint-based; that is the mechanics of the body are described in terms of the forces and moments acting at the joints, and that muscular forces are considered to create moments about the joints. We have recently shown that segment-based approaches, where the mechanics of the body are described by considering the effect of the muscle, ligament and joint contact forces on the segments themselves, can also prove insightful. We have also previously described a simultaneous, optimization based, musculoskeletal model of the lower limb. However, this prior model incorporates both joint- and segment-based assumptions. The purpose of this study was therefore to develop an entirely segment-based model of the lower limb and to compare its performance to our previous work. The segment-based model was used to estimate the muscle forces found during vertical jumping, which were in turn compared with the muscular activations that have been found in vertical jumping, by using a Geers' metric to quantify the magnitude and phase errors. The segment based model was shown to have a similar ability to estimate muscle forces as a model based upon our previous work. In the future, we will evaluate the ability of the segment-based model to be used to provide results with clinical relevance, and compare its performance to joint-based approaches. The segment-based model described in this article is publicly available as a GUI-based Matlab(r) application and in the original source code (at www.msksoftware.org.uk). PMID- 26543567 TI - The 20-item prosopagnosia index (PI20): a self-report instrument for identifying developmental prosopagnosia. AB - Self-report plays a key role in the identification of developmental prosopagnosia (DP), providing complementary evidence to computer-based tests of face recognition ability, aiding interpretation of scores. However, the lack of standardized self-report instruments has contributed to heterogeneous reporting standards for self-report evidence in DP research. The lack of standardization prevents comparison across samples and limits investigation of the relationship between objective tests of face processing and self-report measures. To address these issues, this paper introduces the PI20; a 20-item self-report measure for quantifying prosopagnosic traits. The new instrument successfully distinguishes suspected prosopagnosics from typically developed adults. Strong correlations were also observed between PI20 scores and performance on objective tests of familiar and unfamiliar face recognition ability, confirming that people have the necessary insight into their own face recognition ability required by a self report instrument. Importantly, PI20 scores did not correlate with recognition of non-face objects, indicating that the instrument measures face recognition, and not a general perceptual impairment. These results suggest that the PI20 can play a valuable role in identifying DP. A freely available self-report instrument will permit more effective description of self-report diagnostic evidence, thereby facilitating greater comparison of prosopagnosic samples, and more reliable classification. PMID- 26543566 TI - Impact behaviour of freeze-dried and fresh pomelo (Citrus maxima) peel: influence of the hydration state. AB - Pomelos (Citrus maxima) are known for their thick peel which-inter alia-serves as energy dissipator when fruits impact on the ground after being shed. It protects the fruit from splitting open and thus enables the contained seeds to stay germinable and to potentially be dispersed by animal vectors. The main part of the peel consists of a parenchymatous tissue that can be interpreted from a materials point of view as open pored foam whose struts are pressurized and filled with liquid. In order to investigate the influence of the water content on the energy dissipation capacity, drop weight tests were conducted with fresh and with freeze-dried peel samples. Based on the coefficient of restitution it was found that freeze-drying markedly reduces the relative energy dissipation capacity of the peel. Measuring the transmitted force during impact furthermore indicated a transition from a uniform collapse of the foam-like tissue to a progressive collapse due to water extraction. Representing the peel by a Maxwell model illustrates that freeze-drying not only drastically reduces the damping function of the dashpots but also stiffens the springs of the model. PMID- 26543570 TI - Photothermal raster image correlation spectroscopy of gold nanoparticles in solution and on live cells. AB - Raster image correlation spectroscopy (RICS) measures the diffusion of fluorescently labelled molecules from stacks of confocal microscopy images by analysing correlations within the image. RICS enables the observation of a greater and, thus, more representative area of a biological system as compared to other single molecule approaches. Photothermal microscopy of gold nanoparticles allows long-term imaging of the same labelled molecules without photobleaching. Here, we implement RICS analysis on a photothermal microscope. The imaging of single gold nanoparticles at pixel dwell times short enough for RICS (60 MUs) with a piezo-driven photothermal heterodyne microscope is demonstrated (photothermal raster image correlation spectroscopy, PhRICS). As a proof of principle, PhRICS is used to measure the diffusion coefficient of gold nanoparticles in glycerol : water solutions. The diffusion coefficients of the nanoparticles measured by PhRICS are consistent with their size, determined by transmission electron microscopy. PhRICS was then used to probe the diffusion speed of gold nanoparticle-labelled fibroblast growth factor 2 (FGF2) bound to heparan sulfate in the pericellular matrix of live fibroblast cells. The data are consistent with previous single nanoparticle tracking studies of the diffusion of FGF2 on these cells. Importantly, the data reveal faster FGF2 movement, previously inaccessible by photothermal tracking, and suggest that inhomogeneity in the distribution of bound FGF2 is dynamic. PMID- 26543571 TI - Silver spoon effects on plumage quality in a passerine bird. AB - A silver spoon effect means that individuals who develop under favourable circumstances enjoy a fitness or performance advantage later in life. While there is large empirical support for silver spoon effects acting on different life history traits in birds, such as survival and reproduction, the evidence for the carry-over effects of rearing conditions on the quality of future plumage generations is lacking. Here, we examined whether abilities of individuals to undergo extensive post-juvenile moult may depend on the quality of juvenile plumage developed during the nestling phase in a small passerine showing large individual variation in the extent of post-juvenile moult, the greenfinch (Carduelis chloris). We found that high structural quality and carotenoid chroma of juvenile feathers were positively linked to the extent of post-juvenile moult in this species, thus allowing young birds to attain more adult-like plumage. Silver spoon effects mediated by the juvenile plumage quality were also found to have other fitness-related consequences, as individuals with high-quality juvenile feathers were in better condition during their first winter. As far as we are aware, the results provide the first correlative evidence for a silver spoon effect acting on general plumage quality in birds. PMID- 26543564 TI - Translational research in kidney transplantation and the role of patient engagement. AB - BACKGROUND: Translational research is an evolving discipline that is intended to bridge the gaps between basic science research, clinical research, and implementation in clinical practice. It is a fluid, multidirectional process that requires strong interdisciplinary collaboration to produce research that is relevant to end-users. PURPOSE OF THIS REVIEW: This review summarizes current perspectives on translational research and outlines its relevance and importance to kidney transplantation research. SOURCES OF INFORMATION: Sources of information used for this review include published reports, articles, and research funding websites. FINDINGS: Tissue typing is used as an in-depth example of how translational research has been applied in the field of kidney transplant medicine, and how it has resulted in successful implementation of diagnostic and management options for sensitized individuals undergoing kidney transplantation. The value of actively involving kidney transplant stakeholders (patients, caregivers, and clinicians) in setting research priorities and determining relevant outcomes for future investigation is also discussed. LIMITATIONS: This is a narrative review of the literature which has been partly influenced by the perspectives and experiences of its authors. IMPLICATIONS: Translational and patient-oriented research practices should be incorporated into future research endeavours in the field of kidney transplantation in order to create beneficial change in clinical practice and improve patient outcomes. WHAT WAS KNOWN BEFORE: Translational research which engages patients in the investigative process can enhance the likelihood that medical discoveries will have a meaningful impact at the bedside. WHAT THIS ADDS: This article applies current perspectives on translational research and patient engagement to the field of kidney transplantation, illustrating how these approaches have led to significant advancements in the field. It provides further justification for deliberate, targeted efforts to cross-collaborate and incorporate the patient voice into kidney transplant research. PMID- 26543573 TI - Isothermal pumping analysis for high-altitude tethered balloons. AB - High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe. PMID- 26543572 TI - Spatial modelling of type II diabetes outcomes: a systematic review of approaches used. AB - With the rising incidence of type II diabetes mellitus (DM II) worldwide, methods to identify high-risk geographical areas have become increasingly important. In this comprehensive review following Cochrane Collaboration guidelines, we outline spatial methods, outcomes and covariates used in all spatial studies involving outcomes of DM II. A total of 1894 potentially relevant citations were identified. Studies were included if spatial methods were used to explore outcomes of DM II or type I and 2 diabetes combined. Descriptive tables were used to summarize information from included studies. Ten spatial studies conducted in the USA, UK and Europe met selection criteria. Three studies used Bayesian generalized linear mixed modelling (GLMM), three used classic generalized linear modelling, one used classic GLMM, two used geographic information systems mapping tools and one compared case:provider ratios across regions. Spatial studies have been effective in identifying high-risk areas and spatial factors associated with DM II outcomes in the USA, UK and Europe, and would be useful in other parts of the world for allocation of additional services to detect and manage DM II early. PMID- 26543574 TI - Position-dependent hearing in three species of bushcrickets (Tettigoniidae, Orthoptera). AB - A primary task of auditory systems is the localization of sound sources in space. Sound source localization in azimuth is usually based on temporal or intensity differences of sounds between the bilaterally arranged ears. In mammals, localization in elevation is possible by transfer functions at the ear, especially the pinnae. Although insects are able to locate sound sources, little attention is given to the mechanisms of acoustic orientation to elevated positions. Here we comparatively analyse the peripheral hearing thresholds of three species of bushcrickets in respect to sound source positions in space. The hearing thresholds across frequencies depend on the location of a sound source in the three-dimensional hearing space in front of the animal. Thresholds differ for different azimuthal positions and for different positions in elevation. This position-dependent frequency tuning is species specific. Largest differences in thresholds between positions are found in Ancylecha fenestrata. Correspondingly, A. fenestrata has a rather complex ear morphology including cuticular folds covering the anterior tympanal membrane. The position-dependent tuning might contribute to sound source localization in the habitats. Acoustic orientation might be a selective factor for the evolution of morphological structures at the bushcricket ear and, speculatively, even for frequency fractioning in the ear. PMID- 26543575 TI - Consistent individual differences in haemolymph density reflect risk propensity in a marine invertebrate. AB - While the literature on consistent individual differences in correlated suites of physiological and behavioural traits is steadily growing for vertebrates, invertebrates have received less attention. The few studies that do exist have measured temporary physiological states (or responses), rather than consistent individual physiological traits. Here, I explore the consistency of individual differences in physiology and behaviour of n=53 shore crabs (Carcinus maenas) by repeatedly measuring haemolymph density (HD) and the crabs' responses to a novel environment. In crustaceans, HD is directly proportional to protein concentrations, and thus indicative of physiological condition. HD was highly repeatable, and crabs showed consistent individual differences in their behavioural responses to a novel environment, thus indicating individual consistency in both physiology and behaviour. Furthermore, HD was significantly correlated with the crabs' risk propensity, i.e. individuals with higher HD spent more time near shelter. Overall, this provides the first evidence for consistency in an endogenous physiological trait in an invertebrate. The link between consistent physiology and behaviour, i.e. coping styles, analogous to those found in vertebrates, suggests metabolic and/or immunological correlates of personality which offer great potential for future studies. PMID- 26543576 TI - First indications that northern bottlenose whales are sensitive to behavioural disturbance from anthropogenic noise. AB - Although northern bottlenose whales were the most heavily hunted beaked whale, we have little information about this species in its remote habitat of the North Atlantic Ocean. Underwater anthropogenic noise and disruption of their natural habitat may be major threats, given the sensitivity of other beaked whales to such noise disturbance. We attached dataloggers to 13 northern bottlenose whales and compared their natural sounds and movements to those of one individual exposed to escalating levels of 1-2 kHz upsweep naval sonar signals. At a received sound pressure level (SPL) of 98 dB re 1 MUPa, the whale turned to approach the sound source, but at a received SPL of 107 dB re 1 MUPa, the whale began moving in an unusually straight course and then made a near 180 degrees turn away from the source, and performed the longest and deepest dive (94 min, 2339 m) recorded for this species. Animal movement parameters differed significantly from baseline for more than 7 h until the tag fell off 33-36 km away. No clicks were emitted during the response period, indicating cessation of normal echolocation-based foraging. A sharp decline in both acoustic and visual detections of conspecifics after exposure suggests other whales in the area responded similarly. Though more data are needed, our results indicate high sensitivity of this species to acoustic disturbance, with consequent risk from marine industrialization and naval activity. PMID- 26543577 TI - Experimental evidence for convergent evolution of maternal care heuristics in industrialized and small-scale populations. AB - Maternal care decision rules should evolve responsiveness to factors impinging on the fitness pay-offs of care. Because the caretaking environments common in industrialized and small-scale societies vary in predictable ways, we hypothesize that heuristics guiding maternal behaviour will also differ between these two types of populations. We used a factorial vignette experiment to elicit third party judgements about likely caretaking decisions of a hypothetical mother and her child when various fitness-relevant factors (maternal age and access to resources, and offspring age, sex and quality) were varied systematically in seven populations-three industrialized and four small-scale. Despite considerable variation in responses, we found that three of five main effects, and the two severity effects, exhibited statistically significant industrialized/ small-scale population differences. All differences could be explained as adaptive solutions to industrialized versus small-scale caretaking environments. Further, we found gradients in the relationship between the population-specific estimates and national-level socio-economic indicators, further implicating important aspects of the variation in industrialized and small-scale caretaking environments in shaping heuristics. Although there is mounting evidence for a genetic component to human maternal behaviour, there is no current evidence for interpopulation variation in candidate genes. We nonetheless suggest that heuristics guiding maternal behaviour in diverse societies emerge via convergent evolution in response to similar selective pressures. PMID- 26543578 TI - Computational model of collective nest selection by ants with heterogeneous acceptance thresholds. AB - Collective decision-making is a characteristic of societies ranging from ants to humans. The ant Temnothorax albipennis is known to use quorum sensing to collectively decide on a new home; emigration to a new nest site occurs when the number of ants favouring the new site becomes quorate. There are several possible mechanisms by which ant colonies can select the best nest site among alternatives based on a quorum mechanism. In this study, we use computational models to examine the implications of heterogeneous acceptance thresholds across individual ants in collective nest choice behaviour. We take a minimalist approach to develop a differential equation model and a corresponding non-spatial agent-based model. We show, consistent with existing empirical evidence, that heterogeneity in acceptance thresholds is a viable mechanism for efficient nest choice behaviour. In particular, we show that the proposed models show speed-accuracy trade-offs and speed-cohesion trade-offs when we vary the number of scouts or the quorum threshold. PMID- 26543579 TI - RNA-directed epigenetic silencing of Periostin inhibits cell motility. AB - The over-expression of Periostin, a member of the fasciclin family of proteins, has been reported in a number of cancers and, in particular, in metastatic tumours. These include breast, ovarian, lung, colon, head and neck, pancreatic, prostate, neuroblastoma and thyroid cancers. It is thought that Periostin plays a major role in the development of metastases owing to its apparent involvement in restructuring of the extracellular matrix to create a microenvironment favouring invasion and metastases, angiogenesis, independent proliferation, avoidance of apoptosis and the ability for cells to re-enter the cell cycle. As such we reasoned that targeted suppression of Periostin at the promoter and epigenetic level could result in the stable inhibition of cell motility. We find here that promoter-directed small antisense non-coding RNAs can induce transcriptional gene silencing of Periostin that results ultimately in a loss of cellular motility. The observations presented here suggest that cell motility and possibly metastasis can be controlled by transcriptional and epigenetic regulation of Periostin, offering a potentially new and novel manner to control the spread of cancerous cells. PMID- 26543580 TI - An efficient interpolation technique for jump proposals in reversible-jump Markov chain Monte Carlo calculations. AB - Selection among alternative theoretical models given an observed dataset is an important challenge in many areas of physics and astronomy. Reversible-jump Markov chain Monte Carlo (RJMCMC) is an extremely powerful technique for performing Bayesian model selection, but it suffers from a fundamental difficulty and it requires jumps between model parameter spaces, but cannot efficiently explore both parameter spaces at once. Thus, a naive jump between parameter spaces is unlikely to be accepted in the Markov chain Monte Carlo (MCMC) algorithm and convergence is correspondingly slow. Here, we demonstrate an interpolation technique that uses samples from single-model MCMCs to propose intermodel jumps from an approximation to the single-model posterior of the target parameter space. The interpolation technique, based on a kD-tree data structure, is adaptive and efficient in modest dimensionality. We show that our technique leads to improved convergence over naive jumps in an RJMCMC, and compare it to other proposals in the literature to improve the convergence of RJMCMCs. We also demonstrate the use of the same interpolation technique as a way to construct efficient 'global' proposal distributions for single-model MCMCs without prior knowledge of the structure of the posterior distribution, and discuss improvements that permit the method to be used in higher dimensional spaces efficiently. PMID- 26543581 TI - Incubator-independent cell-culture perfusion platform for continuous long-term microelectrode array electrophysiology and time-lapse imaging. AB - Most in vitro electrophysiology studies extract information and draw conclusions from representative, temporally limited snapshot experiments. This approach bears the risk of missing decisive moments that may make a difference in our understanding of physiological events. This feasibility study presents a simple benchtop cell-culture perfusion system adapted to commercial microelectrode arrays (MEAs), multichannel electrophysiology equipment and common inverted microscopy stages for simultaneous and uninterrupted extracellular electrophysiology and time-lapse imaging at ambient CO2 levels. The concept relies on a transparent, replica-casted polydimethylsiloxane perfusion cap, gravity- or syringe-pump-driven perfusion and preconditioning of pH-buffered serum-free cell-culture medium to ambient CO2 levels at physiological temperatures. The low-cost microfluidic in vitro enabling platform, which allows us to image cultures immediately after cell plating, is easy to reproduce and is adaptable to the geometries of different cell-culture containers. It permits the continuous and simultaneous multimodal long-term acquisition or manipulation of optical and electrophysiological parameter sets, thereby considerably widening the range of experimental possibilities. Two exemplary proof-of-concept long-term MEA studies on hippocampal networks illustrate system performance. Continuous extracellular recordings over a period of up to 70 days revealed details on both sudden and gradual neural activity changes in maturing cell ensembles with large intra-day fluctuations. Correlated time-lapse imaging unveiled rather static macroscopic network architectures with previously unreported local morphological oscillations on the timescale of minutes. PMID- 26543582 TI - A cryptic Allee effect: spatial contexts mask an existing fitness-density relationship. AB - Current theories predict that Allee effects should be widespread in nature, but there is little consistency in empirical findings. We hypothesized that this gap can arise from ignoring spatial contexts (i.e. spatial scale and heterogeneity) that potentially mask an existing fitness-density relationship: a 'cryptic' Allee effect. To test this hypothesis, we analysed how spatial contexts interacted with conspecific density to influence the fertilization rate of the freshwater mussel Margaritifera laevis. This sessile organism has a simple fertilization process whereby females filter sperm from the water column; this system enabled us to readily assess the interaction between conspecific density and spatial heterogeneity (e.g. flow conditions) at multiple spatial levels. Our findings were twofold. First, positive density-dependence in fertilization was undetectable at a population scale (approx. less than 50.5 m(2)), probably reflecting the exponential decay of sperm density with distance from the sperm source. Second, the Allee effect was confirmed at a local level (0.25 m(2)), but only when certain flow conditions were met (slow current velocity and shallow water depth). These results suggest that spatial contexts can mask existing Allee effects. PMID- 26543583 TI - Unnoticed in the tropics: phylogenomic resolution of the poorly known arachnid order Ricinulei (Arachnida). AB - Ricinulei are among the most obscure and cryptic arachnid orders, constituting a micro-diverse group with extreme endemism. The 76 extant species described to date are grouped in three genera: Ricinoides, from tropical Western and Central Africa, and the two Neotropical genera Cryptocellus and Pseudocellus. Until now, a single molecular phylogeny of Ricinulei has been published, recovering the African Ricinoides as the sister group of the American Pseudocellus and providing evidence for the diversification of the order pre-dating the fragmentation of Gondwana. Here, we present, to our knowledge, the first phylogenomic study of this neglected arachnid order based on data from five transcriptomes obtained from the five major mitochondrial lineages of Ricinulei. Our results, based on up to more than 2000 genes, strongly support a clade containing Pseudocellus and Cryptocellus, constituting the American group of Ricinulei, with the African Ricinoides nesting outside. Our dating of the diversification of the African and American clades using a 76 gene data matrix with 90% gene occupancy indicates that this arachnid lineage was distributed in the South American, North American and African plates of Gondwana and that its diversification is concordant with a biogeographic scenario (both for pattern and tempo) of Gondwanan vicariance. PMID- 26543584 TI - Unexpected monophyletic origin of Ephoron shigae unisexual reproduction strains and their rapid expansion across Japan. AB - The burrowing polymitarcyid mayfly Ephoron shigae is distributed across Japan, Korea, northeast China and far east Russia. Some populations are bisexual, and others are unisexual, i.e. geographically parthenogenetic throughout Japan. In general, parthenogenetic organisms are often found in harsh environments, such as at high latitudes and altitudes, in xeric as opposed to mesic conditions, in isolated habitats such as islands and island-like areas, and at the peripheral regions of the taxon's range. In E. shigae, however, the distributions of bisexual and unisexual populations overlap broadly in their respective geographical ranges. In the analysis of mitochondrial 16S rRNA and COI, we revealed that unisexual populations were of monophyletic origin and recently differentiated somewhere in western Japan. In the nuclear DNA EFI-alpha analysis, parthenogenetic strains had two genotypes, i.e. the heterozygous genotype of E1/E3 and the homozygous genotype of E1/E1 or E3/E3, while specimens of bisexual lineage had 20 genotypes. These results are consistent with an automixis mode of reproduction for the parthenogenetic strains, and also support the monophyletic origin of the parthenogenetic strains. Furthermore, there would be no gene flow between the specimens of the bisexual lineage and those of the parthenogenetic strain. PMID- 26543586 TI - Image analysis of weaverbird nests reveals signature weave textures. AB - In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests. PMID- 26543585 TI - Phenotype-limited distributions: short-billed birds move away during times that prey bury deeply. AB - In our seasonal world, animals face a variety of environmental conditions in the course of the year. To cope with such seasonality, animals may be phenotypically flexible, but some phenotypic traits are fixed. If fixed phenotypic traits are functionally linked to resource use, then animals should redistribute in response to seasonally changing resources, leading to a 'phenotype-limited' distribution. Here, we examine this possibility for a shorebird, the bar-tailed godwit (Limosa lapponica; a long-billed and sexually dimorphic shorebird), that has to reach buried prey with a probing bill of fixed length. The main prey of female bar tailed godwits is buried deeper in winter than in summer. Using sightings of individually marked females, we found that in winter only longer-billed individuals remained in the Dutch Wadden Sea, while the shorter-billed individuals moved away to an estuary with a more benign climate such as the Wash. Although longer-billed individuals have the widest range of options in winter and could therefore be selected for, counterselection may occur during the breeding season on the tundra, where surface-living prey may be captured more easily with shorter bills. Phenotype-limited distributions could be a widespread phenomenon and, when associated with assortative migration and mating, it may act as a precursor of phenotypic evolution. PMID- 26543587 TI - Rethinking competence in marine life cycles: ontogenetic changes in the settlement response of sand dollar larvae exposed to turbulence. AB - Complex life cycles have evolved independently numerous times in marine animals as well as in disparate algae. Such life histories typically involve a dispersive immature stage followed by settlement and metamorphosis to an adult stage on the sea floor. One commonality among animals exhibiting transitions of this type is that their larvae pass through a 'precompetent' period in which they do not respond to localized settlement cues, before entering a 'competent' period, during which cues can induce settlement. Despite the widespread existence of these two phases, relatively little is known about how larvae transition between them. Moreover, recent studies have blurred the distinction between the phases by demonstrating that fluid turbulence can spark precocious activation of competence. Here, we further investigate this phenomenon by exploring how larval interactions with turbulence change across ontogeny, focusing on offspring of the sand dollar Dendraster excentricus (Eschscholtz). Our data indicate that larvae exhibit increased responsiveness to turbulence as they get older. We also demonstrate a likely cost to precocious competence: the resulting juveniles are smaller. Based upon these findings, we outline a new, testable conception of competence that has the potential to reshape our understanding of larval dispersal and connectivity among marine populations. PMID- 26543588 TI - Tools to tipple: ethanol ingestion by wild chimpanzees using leaf-sponges. AB - African apes and humans share a genetic mutation that enables them to effectively metabolize ethanol. However, voluntary ethanol consumption in this evolutionary radiation is documented only in modern humans. Here, we report evidence of the long-term and recurrent ingestion of ethanol from the raffia palm (Raphia hookeri, Arecaceae) by wild chimpanzees (Pan troglodytes verus) at Bossou in Guinea, West Africa, from 1995 to 2012. Chimpanzees at Bossou ingest this alcoholic beverage, often in large quantities, despite an average presence of ethanol of 3.1% alcohol by volume (ABV) and up to 6.9% ABV. Local people tap raffia palms and the sap collects in plastic containers, and chimpanzees use elementary technology-a leafy tool-to obtain this fermenting sap. These data show that ethanol does not act as a deterrent to feeding in this community of wild apes, supporting the idea that the last common ancestor of living African apes and modern humans was not averse to ingesting foods containing ethanol. PMID- 26543589 TI - Eye-spots in Lepidoptera attract attention in humans. AB - Many prey species exhibit defensive traits to decrease their chances of predation. Conspicuous eye-spots, concentric rings of contrasting colours, are one type of defensive trait that some species exhibit to deter predators. We examined the function of eye-spots in Lepidoptera to determine whether they are effective at deterring predators because they resemble eyes ('eye mimicry hypothesis') or are highly salient ('conspicuous signal hypothesis'). We recorded the gaze behaviour of men and women as they viewed natural images of butterflies and moths as well as images in which the eye-spots of these insects were modified. The eye-spots were modified by removing them, scrambling their colours, or replacing them with elliptical or triangular shapes that had either dark or light centres. Participants were generally more likely to look at, spend more time looking at and be faster to first fixate the eye-spots of butterflies and moths that were natural compared with ones that were modified, including the elliptical eye-spots with dark centres that most resembled eyes as well as the scrambled eye-spots that had the same contrast as the natural eye-spots. Participants were most likely to look at eye-spots that were numerous, had a large surface area and were located close to the insects' heads. Participants' pupils were larger when viewing eye-spots compared with the rest of the insects' body, suggesting a greater arousal when viewing eye-spots. Our results provide some support for the conspicuous signal hypothesis (and minimal support for the eye mimicry hypothesis) and suggest that eye-spots may be effective at deterring predators because they are highly conspicuous signals that draw attention. PMID- 26543590 TI - Erratum: Atomic scale modelling of hexagonal structured metallic fission product alloys. AB - [This corrects the article DOI: 10.1098/rsos.140292.]. PMID- 26543591 TI - Himalayan dock (Rumex nepalensis): the flip side of obnoxious weed. AB - Himalayan dock (Rumex nepalensis) was evaluated for forage value and antinutrients under three, five and seven weeks cutting intervals in the temperate environment. Dry matter (DM) content was measured for each cutting interval. Forage quality parameters such as Crude Protein (CP), Acid Detergent fiber (ADF), Neutral Detergent Fiber (NDF), Calcium (Ca) and Phosphorus (P) were analyzed. Plants with seven weeks cutting interval gave higher DM yield. CP and P content were significantly higher for three weeks cutting intervals. Average CP contents were 31.38 %, 30.73 % and 27.32 % and average P content 0.58 %, 0.52 % and 0.51 % for three, five and seven weeks cutting intervals, respectively. Ca content did not differ significantly between cutting intervals. The average Ca content were 0.91 %, 0.90 % and 90 %, for three, five and seven weeks cutting intervals, respectively. Tannin and mimosine contents were not significantly different between cutting intervals. Average tannin contents were 1.32 %, 1.27 % and 1.26 % and mimosine 0.38 %, 0.30 % and 0.28 % for three, five and seven weeks cutting intervals, respectively. The study concluded that R. nepalensis could be a potential source of protein for livestock. The study also suggests seven weeks harvesting interval to provide plants with high dry matter yield, high forage quality and very low levels of anti-nutrients. PMID- 26543593 TI - Preface to focused issue on current challenges in transcatheter valve therapies. PMID- 26543592 TI - Effect of topographical control by a micro-molding process on the activity of human Mesenchymal Stem Cells on alumina ceramics. AB - BACKGROUND: Numerous studies have reported that microgrooves on metal and polymer materials can affect cell adhesion, proliferation, differentiation and guidance. However, our knowledge of the cell activity associated with microgrooves on ceramics, such as alumina, zirconia, hydroxyapatite and etc, is very incomplete, owing to difficulties in the engraving of microgrooves on the hard surface of the base material. In this study, microgrooves on alumina were fabricated by a casting process using a polydimethylsiloxane micro-mold. The cell responses of Human Mesenchymal Stem Cells on the alumina microgrooves were then evaluated. RESULTS: Microgrooves on an alumina surface by micro-mold casting can enhance the adhesion, differentiation of osteoblasts as well as gene expression related to osteoblast differentiation. The ALP activity and calcium concentration of the cells on alumina microgrooves were increased by more than twice compared to a non microgrooved alumina surface. Moreover, regarding the osteoblast differentiation of hMSCs, the expression of ALP, RUNX2, OSX, OC and OPN on the microgrooved alumina were all significantly increased by 1.5 ~ 2.5 fold compared with the non microgrooved alumina. CONCLUSION: Altering the topography on alumina by creating microgrooves using a micro-molding process has an important impact on the behavior of hMSCs, including the adhesion, differentiation of osteoblasts and osteoblast-specific gene expression. The significant increase in hMSC activity is explained by the increasing of material transportation in parallel direction and by the extending of spreading distance in perpendicular direction. PMID- 26543594 TI - Redo aortic valve surgery versus transcatheter valve-in-valve implantation for failing surgical bioprosthetic valves: consecutive patients in a single-center setting. AB - BACKGROUND: Due to a considerable rise in bioprosthetic as opposed to mechanical valve implantations, an increase of patients presenting with failing bioprosthetic surgical valves in need of a reoperation is to be expected. Redo surgery may pose a high-risk procedure. Transcatheter aortic valve-in-valve implantation is an innovative, less-invasive treatment alternative for these patients. However, a comprehensive evaluation of the outcome of consecutive patients after a valve-in-valve TAVI [transcatheter aortic valve-in-surgical aortic valve (TAV-in-SAV)] as compared to a standard reoperation [surgical aortic valve redo-operation (SAV-in-SAV)] has not yet been performed. The goal of this study was to compare postoperative outcomes after TAV-in-SAV and SAV-in-SAV in a single center setting. METHODS: All SAV-in-SAV and TAV-in-SAV patients from January 2001 to October 2014 were retrospectively reviewed. Patients with previous mechanical or transcatheter valves, active endocarditis and concomitant cardiac procedures were excluded. Patient characteristics, preoperative data, post-procedural complications, and 30-day mortality were collected from a designated database. Mean values +/- SD were calculated for all continuous variables. Counts and percentages were calculated for categorical variables. The Chi-square and Fisher exact tests were used to compare categorical variables. Continuous variables were compared using the t-test for independent samples. A 2 sided P value <0.05 was considered statistically significant. RESULTS: A total of 102 patients fulfilled the inclusion criteria, 50 patients (49%) underwent a transcatheter valve-in-valve procedure, while 52 patients (51%) underwent redo surgery. Patients in the TAV-in-SAV group were significantly older, had a higher mean logistic EuroSCORE and exhibited a lower mean left ventricular ejection fraction than patients in the SAV-in-SAV group (78.1+/-6.7 vs. 66.2+/-13.1, P<0.001; 27.4+/-18.7 vs. 14.4+/-10, P<0.001; and 49.8+/-13.1 vs. 56.7+/-15.8, P=0.019 respectively). Postoperative pacemaker implantation and chest tube output were higher in the SAV-in-SAV group compared to the TAV-in-SAV group [11 (21%) vs. 3 (6%), P=0.042 and 0.9+/-1.0 vs. 0.6+/-0.9, P=0.047, respectively]. There was no significant difference in myocardial infarction, stroke or dialysis postoperatively. Thirty-day mortality was not significantly different between the two groups [TAV-in-SAV2 (4%) vs. SAV-in-SAV0, P=0.238]. Kaplan-Meier (KM) 1-year survival was significantly lower in the TAV-in-SAV group than in the SAV-in-SAV group (83% vs. 96%, P<0.001). CONCLUSIONS: The present investigation shows that both groups, irrespective of different baseline comorbidities, show very good early clinical outcomes. While redo surgery is still the standard of care, a subgroup of patients may profit from the transcatheter valve-in-valve procedure. PMID- 26543595 TI - Challenges in valve-in-valve therapy. AB - At present, the majority of surgical heart valves (SHVs) implanted are bioprosthetic valves. Over time however, these are prone to structural deterioration, which may manifest as valvular stenosis, regurgitation or a combination of the two. Re-operation is the current standard of care for these patients but this itself carries a significant risk of mortality and morbidity. As a natural extension of transcatheter aortic valve implantation (TAVI), now an evidence based solution for severe aortic stenosis in high-risk patients, valve in-valve (VIV) therapy is evolving into an alternative option in selected patients with structural biological valvular deterioration in all four-valve positions. The first of these VIV procedures was performed in Germany in 2007, for failing aortic valve prosthesis and later, reported in other positions. As with any novel emerging therapy, there is a learning curve to the procedure and the operator must be aware of the potential challenges. In this review we describe some of these challenges with the aim of providing awareness as well as guidance on attaining a successful outcome. PMID- 26543596 TI - MitraClip-data analysis of contemporary literature. AB - Treatment of mitral regurgitation (MR) with the MitraClip (MC), a percutaneous, transseptal edge-to-edge reconstruction of the mitral valve, has become an interesting treatment option in most patients not eligible for surgery. Lately a variety of studies have been published analyzing the treatment of MR with the MC in degenerative as well as functional MR. The results for both entities of MR show negligible intraprocedural mortality, low periprocedural complications rates and a beneficiary outcome in terms of reduction in MR as well as an improvement in functional capacity and quality of life. Here we summarize the latest results focusing on safety and efficacy of MC treatment. PMID- 26543597 TI - Sedation or general anesthesia for transcatheter aortic valve implantation (TAVI). AB - Transfemoral transcatheter aortic valve implantation (TAVI) is nowadays a routine therapy for elderly patients with severe aortic stenosis (AS) and high perioperative risk. With growing experience, further development of the devices, and the expansion to "intermediate-risk" patients, there is increasing interest in performing this procedure under conscious sedation (TAVI-S) rather than the previously favoured approach of general anesthesia (TAVI-GA). The proposed benefits of TAVI-S include; reduced procedure time, shorter intensive care unit (ICU) length of stay, reduced need for intraprocedural vasopressor support, and the potential to perform the procedure without the direct presence of an anesthetist for cost-saving reasons. To date, no randomized trial data exists. We reviewed 13 non-randomized studies/registries reporting data from 6,718 patients undergoing TAVI (3,227 performed under sedation). Patient selection, study methods, and endpoints have differed considerably between published studies. Reported rates of in-hospital and longer-term mortality are similar for both groups. Up to 17% of patients undergoing TAVI-S require conversion to general anesthesia during the procedure, primarily due to vascular complications, and urgent intubation is frequently associated with hemodynamic instability. Procedure related factors, including hypotension, may compound preexisting age specific renal impairment and enhance the risk of acute kidney injury. Hypotonia of the hypopharyngeal muscles in elderly patients, intraprocedural hypercarbia, and certain anesthetic drugs, may increase the aspiration risk in sedated patients. General anesthesia and conscious sedation have both been used successfully to treat patients with severe AS undergoing TAVI with similar reported short and long-term mortality outcomes. The authors believe that the significant incidence of complications and unplanned conversion to general anesthesia during TAVI-S mandates the start-to-finish presence of an experienced cardiac anesthetist in order to optimize patient outcomes. Good quality randomized data is needed to determine the optimal anesthetic regimen for patients undergoing TAVI. PMID- 26543598 TI - Acute kidney injury after transcatheter aortic valve implantation. AB - Even though experience and techniques have constantly improved over the last years, peri- and postprocedural complications in high risk TAVI-collectives remain a major issue affecting outcome and survival. Acute kidney injury (AKI) is a frequent complication after transcatheter aortic valve implantation (TAVI) and effects outcome and survival. However, the definition of AKI in published studies dealing with the phenomenon of AKI after TAVI varies widely and lacks standardization. This Review aims to present an overview over the current literature concerning AKI after TAVI with regard to the definition of AKI, the impact of AKI on mortality and potential risk factors for renal impairment after TAVI. PMID- 26543599 TI - Current challenges in interventional mitral valve treatment. AB - Transcatheter mitral valve therapies have emerged as an alternative option in high surgical risk or inoperable patients with severe and symptomatic mitral regurgitation (MR). As multiple technologies and different approaches will become available in the field of mitral valve interventions, different challenges are emerging, both patient- (clinical challenges) and procedure-related (technical challenges). This review will briefly explore the current open challenges in the evolving fields of interventional mitral valve treatment. PMID- 26543600 TI - Preferential short cut or alternative route: the transaxillary access for transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation (TAVI) has gained widespread acceptance as a treatment option for patients at high risk for conventional aortic valve replacement. The most commonly used access site for TAVI is the common femoral artery. Yet, in a significant number of patients the transfemoral access is not suitable due to peripheral vascular disease of the lower extremity. In these cases the transaxillary approach can serve as an alternative implantation route. By considering the anatomical requirements and providing an adequate endovascular "safety-net" during the procedure the transaxillary TAVI approach results in excellent procedural and clinical outcome. However, whether the transaxillary access for TAVI is superior to other non-transfemoral approaches (e.g., transapical or direct aortic) needs to be studied in the future in a prospective randomized trial. PMID- 26543601 TI - Access and closure of the left ventricular apex: state of play. AB - Calcific aortic stenosis is the most frequent manifestation of valvular heart disease. The preferred treatment for patients of all age groups is surgical aortic valve replacement. Recently, transcatheter aortic valve implantation (TAVI) has become the standard of care for patients that are deemed to be at high risk for open heart surgery. The most common access route for TAVI is the retrograde transfemoral (TF) approach, followed by the antegrade transapical (TA) approach. Both access routes have distinct indications. While the TF route is least invasive and the access of choice at most centers, the apical route is used complementary in patients with poor femoral access. In addition, the TA approach holds various benefits such as a short distance from the operator to the annulus facilitating exact positioning of the valve and the possibility to accommodate larger sheaths. Furthermore, the TA approach not only provides direct access to the aortic valve but also the mitral valve allowing for a wide range of interventions. Various apical closure devices are currently being developed under the premise of increasing overall safety of the TA-TAVI approach by further standardizing the procedure, alleviating left ventricular access and minimizing the risk of complications, such as apical bleeding. The aim of this article is to give an overview of current devices for apical closure. The ideal apical closure device should be easy to put in place, leave a minimum of foreign material, provide complete hemostasis and have a minimal risk of displacement. So far the range of commercially available devices in Europe is very limited with only one CE-certified device on the market and one device that is expected to receive CE certification soon. Off-the-shelf closure devices could help flatten the initial operator learning curve and facilitate a safe apical access, ultimately leading to an entirely percutaneous TA-TAVI approach. PMID- 26543602 TI - Detection of rearrangement of anaplastic lymphoma kinase (ALK) and mutation of epidermal growth factor receptor (EGFR) in primary pulmonary lymphoepithelioma like carcinoma. AB - BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a distinct rare subtype of lung cancer. The prevalence of anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutation in primary pulmonary LELC had not been thoroughly investigated. METHODS: We investigated a cohort of 42 patients with primary pulmonary LELC and genotyped for ALK rearrangement and EGFR mutation. ALK rearrangement was detected by fluorescence in situ hybridization (FISH). EGFR mutational analysis of exons 18 through 21 was analyzed by TaqMan real-time polymerase chain reaction (PCR). RESULTS: Epstein-Barr virus-encoded RNAs (EBERs) showed positive signals in all 42 patients. By immunohistochemistry staining, all patients demonstrated positive expression of CK5/6 and P63, but almost all patients were negative for TTF-1 (34/34, 100%) or CK7 (34/35, 97.1%). None of the 42 patients had ALK rearrangement. Of 42 patients tested, only one patient (2.4%) harbored L858R mutation and gefitinib was applied to this case, however no objective response was observed and the progression free survival (PFS) time was only 1 month. CONCLUSIONS: Primary pulmonary LELC is a unique histological subtype of lung cancer. ALK rearrangement and EGFR mutation are lack and they may not be the oncogenic driver gene in pulmonary LELC. Future efforts should be made to explore other oncogenic driver gene to guide targeted therapy in this rare disease to determine the optimal treatment. PMID- 26543603 TI - miR-132 inhibits lung cancer cell migration and invasion by targeting SOX4. AB - BACKGROUND: Multiple MicroRNAs (miRNAs) have been identified in the development and progression of lung cancer. However, the expression and roles of miR-132 in non-small cell lung cancer (NSCLC) remain largely undefined. The aim of this study is to investigate the biological functions and its molecular mechanisms of miR-132 in human lung cancer cells. METHODS: miR-132 expression was measured in human lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The cells migration and invasion ability were measured by wound healing assay and transwell assay. The influence of miR-132 on tumor progression in vivo was monitored using NSCLC xenografts in nude mice. The target gene of miR-132 was determined by luciferase assay and western blot. RESULTS: The expression level of miR-132 was dramatically decreased in examined lung cancer cell lines. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro. Besides, miR-132 overexpression could also inhibit tumor growth in the nude mice. Further studies indicated that the sex determining region Y-box 4 (SOX4) is a target gene of miR-132. SOX4 re-introduction could reverse the anti-invasion role of miR-132. CONCLUSIONS: Our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-132 may serve as a potential target in the treatment of human lung cancer. PMID- 26543604 TI - miR-1290 is a potential prognostic biomarker in non-small cell lung cancer. AB - BACKGROUND: miR-1290 is a newly discovered microRNA (miRNA), and its role in non small cell lung cancer (NSCLC) remains unknown. This study aimed to evaluate the expression levels of miR-1290 in NSCLC tissues and serum, and explore its associations with clinicopathological characteristics and prognosis of NSCLC patients. METHODS: A total of 33 pairs of tissues and 73 serum samples were obtained from NSCLC patients and expression levels of miR-1290 were detected by specific TaqMan qRT-PCR. The relationship between miR-1290 expression levels in NSCLC tissues and serum and clinicopathological characteristics was estimated respectively. The correlation between serum miR-1290 expression levels and overall survival of NSCLC patients was performed by Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: We determined that miR-1290 expression levels were increased significantly in NSCLC tissues compared with non-tumor adjacent normal tissues, and higher miR-1290 expression levels were positively correlated with high tumor stage (P=0.004) and positive lymph node metastasis (P=0.013). Compared with benign lung disease and healthy controls, serum levels of NSCLC patients exhibited higher expression of miR-1290. Furthermore, the up regulation of serum miR-1290 more frequently occurred in NSCLC patients with high TNM stage, positive lymph node metastasis (P=0.022 and P=0.024, respectively). Kaplan-Meier analysis demonstrated that high serum miR-1290 expression levels predicted poor survival (P=0.022). Cox proportional hazards risk analysis indicated that miR-1290 was an independent prognostic factor for NSCLC. CONCLUSIONS: Our study suggests that miR-1290 is overexpressed in NSCLC, and serum miR-1290 may be used as a potential prognostic biomarker for NSCLC. PMID- 26543605 TI - Computed tomography guided microcoil localization for pulmonary small nodules and ground-glass opacity prior to thoracoscopic resection. AB - BACKGROUND: To evaluate the feasibility, safety and efficacy of computed tomography (CT)-guided microcoil localization for small pulmonary lesions prior to thoracoscopic resection. METHODS: We retrospectively reviewed the medical data of patients with pulmonary solid nodules and ground-glass opacity (GGO) who underwent CT-guided microcoil localization prior to thoracoscopic surgery. The microcoil was deployed with the proximal end of the microcoil coiling beyond the parietal pleura while the distal part anchoring in the lung parenchyma. After marking with microcoil, the pulmonary lesions were removed by thoracoscopic surgery. RESULTS: CT-guided microcoil placements were successful in all 98 lesions, including 14 solid nodules, 11 part-solid GGO, and 73 pure GGO. The mean distance from the lesions to the pleura surface was 11.1+/-6.6 mm. Eighty-four microcoils (85.7%) were successfully placed with the tails coiled beyond the parietal pleura. Seventeen patients (17.3%) had mild complications after the procedure of localization. Thirteen patients with asymptomatic pneumothorax, only one patient required further thoracentesis, four patients with pulmonary hematoma. Removal of the pulmonary lesions was successful in all patients. Sixty six lesions (67.3%) were localized through the proximal end of the microcoil beyond the visceral pleura by visual inspection, 29 lesions were localized by palpation of the microcoil or the nodule, and 3 lesions had dislocation of the microcoil, resulting in a success rate of 96.9% for intraoperative localization. CONCLUSIONS: CT-guided microcoil localization prior to thoracoscopic resection is a feasible, safe, and effective method for localization of pulmonary small nodules and GGO. PMID- 26543606 TI - Correlation between epidermal growth factor receptor mutations and nuclear expression of female hormone receptors in non-small cell lung cancer: a meta analysis. AB - BACKGROUND: Compared with male, female non-small cell lung cancer (NSCLC) patients have better response when treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), suggesting a potential association between female hormones and EGFR mutation. However, the results provided by previous studies were inconclusive and controversial. We sought to examine the link between the expression of nuclear female hormone receptors and EGFR mutations in NSCLC. METHODS: Electronic databases were used to search the relevant articles. The involved hormone receptors included estrogen receptor (ER) and progesterone receptor (PR). The primary endpoint was the occurrence of ER/PR expression and EGFR mutation in NSCLC patients. RESULTS: Five studies fulfilled the criteria and were included in our analysis. Patients with high ER-beta expression had higher positive EGFR mutation than low ER-beta patients (44.2% vs. 23.7%), and there was a significant difference between the two groups [odds radio (OR) 3.44, 95% confidence interval (CI): 2.40-4.93, Z=6.72, P<0.001]. However, there is no significant correlation between EGFR mutations and ER-alpha (when included ER-alpha3, OR 1.20, 95% CI: 0.62-2.33, Z=0.55, P=0.58; and when included ER-alpha4, OR 1.18, 95% CI: 0.62-2.25, Z=0.51, P=0.61) or PR (OR 1.29, 95% CI: 0.40-4.10, Z=0.43, P=0.67). No significant publication bias was observed. CONCLUSIONS: High nuclear expression of ER-beta, but not ER-alpha or PR is correlated with EGFR mutations in NSCLC. The underlying mechanism and potential translational relevance warrant further investigation. PMID- 26543607 TI - Surgical correction of 639 pectus excavatum cases via the Nuss procedure. AB - BACKGROUND: To review the clinical experience and short- to middle-term effects of the Nuss procedure for correction of pectus excavatum (PE). METHODS: From September 2006 to August 2014, 639 patients with PE were treated using the Nuss procedure. Of these, 546 were male and 93 were female. The mean age was 15.3+/ 5.8 years (2.5-49 years). Preoperative chest CT scans Haller index (HI) was 4.3+/ 1.7 (2.9-17.4), with 75 cases of mild PE (HI <3.2), 114 cases of moderate PE (HI 3.2-3.5), 393 cases of severe PE (HI 3.6-6.0), and 57 cases of extremely severe PE (HI >6.0). RESULTS: A total of 638 patients successfully completed the surgery, an 11-year-old male patient who died after the surgery had undergone ventricular septal defect closure surgery through a sternal incision 7 years ago. The mean operative time was 64.3+/-41.7 min (40-310 min). Excluding the patient who died, the average blood loss was 24.5+/-17.8 mL (10-160 mL). The average length of postoperative hospital stay was 5.2+/-2.9 days (4-36 days). A total of 484 cases (75.7%) required 1 steel bar insertion, 153 cases (24.0%) required 2 steel bars, and 2 cases (0.3%) required 3 bars. Postoperative evaluation of the surgery outcomes revealed the following: excellent in 504 cases, good in 105, fair in 28 and poor in 2, good quality rate was 95.3%. CONCLUSIONS: Correction of PE via the Nuss procedure is minimally invasive and simple to perform with good short and mid-term effects, while long-term efficacy remains to be determined. PMID- 26543608 TI - Incremental value of contrast enhanced computed tomography on diagnostic accuracy in evaluation of small pulmonary ground glass nodules. AB - BACKGROUND: To evaluate the information gain by the application of both non contrast and contrast enhanced computed tomography (CT) with extended mediastinal display window settings in the evaluation of pure ground glass nodules (pGGNs) and or mixed ground glass nodules (mGGNs) in the context of pre-invasive or early stage lung adenocarcinoma. METHODS: One hundred and fifty patients with ground glass nodules (GGNs) and mGGNs, with contrast enhanced CT scans within 2 weeks of thoracic surgery were included in the study. Quantitative evaluation of all nodules was performed in a conventional mediastinal window (CMW) and an extended mediastinal window (EMW) both on non-contrast images and contrast-enhanced images. RESULTS: Contrast-enhanced images with CMW demonstrated amplification of solid portion in 23 (43%), 41 (77%) with EMW out of 53 minimally invasive adenocarcinoma (MIA) nodules, and in 34 of 37 (91%) of invasive adenocarcinoma (IAC) nodules. Using the increase in size of solid portion of the nodule measured on the enhanced CT images with EMW, area under the receiver operating characteristic (ROC) curve of 0.872 and 0.899 was utilized for differentiating between the pre-invasive nodules and MIA and between MIA and IAC nodules, respectively. Statistically significant differences existed between the pre invasive and the MIA groups, and MIA and the IAC groups in smaller nodules (P<0.01). CONCLUSIONS: Comparative quantitative analysis of the pre and post contrast images can help differentiate between atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), MIAs, and IACs. Extension of the CT mediastinal window setting improves the evaluation of small GGNs, and can augment the diagnostic accuracy when evaluating small pGGNs and mGGNs. PMID- 26543609 TI - Clinical outcomes of surgery after induction treatment in patients with pathologically proven N2-positive stage III non-small cell lung cancer. AB - BACKGROUND: To assess the effect of preoperative neoadjuvant therapy on resectability, downstaging, and the prognosis in patients with stage IIIA-N2 non small cell lung cancer (NSCLC). METHODS: Eighty-four patients who underwent resections after induction therapy [76 with neoadjuvant chemotherapy (CTx) and 8 with induction chemoradiotherapy (CRTx)] for clinically evident [larger than 1 cm on computed tomography (CT)] and pathologically confirmed ipsilateral N2 positive NSCLC (stage IIIA) between January 2009 and July 2013 were reviewed retrospectively. RESULTS: Partial response (PR) was observed in 39 patients (46.4%). Standard lobectomy was performed in 63 cases (75.0%), and extensive resection was conducted in 21 cases (25.0%), including four pneumonectomies. Pathologic nodal downstaging (pN2 to pN0-1) was confirmed in 38 cases (45.2%). After induction therapy plus resection, 5-year progression-free survival (PFS) and overall survival (OS) in cases with radical resections were 37.9% and 34.2%, respectively. Patients who underwent lobectomy or pathologic nodal downstaging had better prognosis than those who had extensive resection or persistent N2 in PFS (P=0.036; P=0.025) and OS (P=0.023; P=0.024). On univariate analysis, lobectomy and pathological nodal downstaging were favourably predictive factors both in PFS and OS. Cox multivariate analyses identified only pathologic nodal downstaging to predict better PFS, and lobectomy to be significantly prognostic for OS. CONCLUSIONS: These data suggest that neoadjuvant therapy was feasible, and helpful for tumor and pathologic nodal downstaging with promising rates of survival in patients with stage IIIA-N2 NSCLC. After induction therapy, patients with potentially radical lobectomy were more likely to benefit from operation. Pathological nodal downstaging of pN2 to pN0-1, rather than clinical response was predictive of a favorable outcome, and was correlated with a better chance of survival. PMID- 26543610 TI - Analysis of pulmonary function test results in a health check-up population. AB - BACKGROUND: To explore the incidences of chronic obstructive pulmonary disease (COPD), obstructive ventilatory dysfunction, and obstructive small airway disease and their risk factors in a health check-up population, with an attempt to inform the early diagnosis and treatment of COPD. METHODS: Subjects who aged 20 years and older and received health check-up in the Health Management Center, Third Xiangya Hospital, Central South University from June 2013 to June 2015 were enrolled in this study. The results of detection and survey for COPD, obstructive ventilatory dysfunction, and obstructive small airway disease were analyzed. RESULTS: Among 6,811 subjects enrolled in this study, the detection rate of COPD, obstructive ventilator dysfunction, and obstructive small airway disease was 0.8%, 2.6%, and 4.0%, respectively, which showed a positive correlation with male gender, age, and smoking index. CONCLUSIONS: Health check-up is an important approach for screening COPD, obstructive ventilator dysfunction, and obstructive small airway disease. Smoking cessation and controlling of relevant risk factors are helpful to lower the incidences of these conditions. PMID- 26543611 TI - The BCL11A-XL expression predicts relapse in squamous cell carcinoma and large cell carcinoma. AB - BACKGROUND: The B cell leukemia 11A (BCL11A) gene was identified as a proto oncogene in hematopoietic cell malignancies and breast cancer. Alternative RNA splicing generates three main transcripts designated as Extra-long (XL; 5.9 kb/125 kD), Long (L; 3.8 kb/100 kD) and Short (S; 2.4 kb/35 kD). Our previous study results demonstrated that BCL11A expression levels were specifically upregulated in non-small cell lung cancer (NSCLC) tissues, especially in squamous cell carcinoma (SCC) and large cell carcinoma (LCC). METHODS: In this study, we detected the BCL11A protein isoforms with immunohistochemistry (IHC) method in NSCLC with in a cohort (n=40) of BCL11A overexpression NSCLC patients. All 40 cases were BCL11A overexpression including 27 SCCs, 8 LCCs and 5 adenocarcinomas (ACs). Relationship between BCL11A isoforms and the clinicopathological parameters were also analyzed. RESULTS: Compare to the BCL11A-L and S isoforms, the BCL11A-XL isoform was specifically expressed in SCC and LCC (P=0.006). There were 19 (19/40, 47.5%) cases positive for BCL11A-XL expression, SCC accounted for 63.2% (12/19) and LCC accounted for 36.8% (7/19). The survival analysis indicated that BCL11A-XL expression was an independent prognostic factor for disease-free survival (DFS) [hazards ratio (HR) 0.246; 95% confidence interval (CI), 0.065 0.939, P=0.040] but not for overall survival (OS) in patients with SCC and LCC. CONCLUSIONS: Our results demonstrated that the BCL11A-XL isoform might be a potential prognostic biomarker of SCC and LCC. PMID- 26543612 TI - Simultaneous thoracoscopic resection for coexisting pulmonary and thymic lesions. AB - BACKGROUND: The management of synchronous thymic and pulmonary lesions remains a challenge due to the lack of case series and surgical guidelines. This study aims to retrospectively review our preliminary experience and results of performing simultaneous thoracoscopic resection of coexisting diseases of the lung and thymus. METHODS: Simultaneous thoracoscopic resection was performed to remove coexisting thymic and pulmonary lesions in nine patients from August 2008 to November 2013. Patient demographics, preoperative assessment, surgical procedures and postoperative course of these patients were reviewed. RESULTS: There were four female and five male patients between 43 and 70 years old (median age, 64 years). Each patient had thymic neoplasm and solitary pulmonary lesion on chest computed tomography (CT) scan. Four patients underwent thoracoscopic lobectomy and thymectomy. One patient had thoracoscopic bronchovascular sleeve lobectomy combined with thymic cyst resection (TCR). The other four patients received pulmonary wedge resection and thymectomy (n=3)/TCR (n=1). The operation lasted from 35-480 min (median, 110 min). Intra-operative blood loss was 20-380 mL (median, 120 mL). Two patients developed post-operative pneumonia without mortality. All the patients were discharged home within 9 days after surgery. Two patients died from metastatic lung cancer 14 months after surgery. CONCLUSIONS: Simultaneous thoracoscopic resection of coexisting pulmonary and thymic lesions is safe and feasible in selected patients. PMID- 26543613 TI - Cost and effectiveness of image-guided radiotherapy for non-operated localized lung cancer: a population-based propensity score-matched analysis. AB - BACKGROUND: Image-guided radiotherapy (IGRT) is a novel technology to enhance RT delivery accuracy. However, the clinical effectiveness and cost-effectiveness are less clear. The aim of our study is to compare the cost and effectiveness of conventional fractionated RT for non-operated localized lung cancer delivered with vs. without IGRT via this population-based propensity score (PS) matched analysis. METHODS: We identified eligible patients diagnosed within 2007-2010 through a comprehensive population-based database containing cancer, death registries, and reimbursement data in Taiwan. The primary duration of interest (DOI) was 2 years within diagnosis. Effectiveness was measured as survival whereas direct medical cost was measured from the payers' perspective. In supplementary analysis (SA), we estimated the cost-effectiveness in consider of out-of-pocket (OOP) payment and 4 years as DOI. RESULTS: Our study population constituted 124 patients. Within 2 years, both the mean cost (2014 USD) and survival (life-year, LY) were higher for IGRT ($60,774 vs. $60,554; 1.43 vs. 1.37). The incremental cost-effectiveness ratio (ICER) when IGRT was compared to non-IGRT was 3,667 (USD/LY). The chance for IGRT to be cost-effective was around 68% & 70% at willingness-to-pay threshold 50,000 USD/LY and 150,000 USD/LY respectively. IGRT remained cost-effective in SA. CONCLUSIONS: We provide the first empirical evidence that when compared to non-IGRT, IGRT was potentially cost-effective. PMID- 26543614 TI - Prevalence survey of nosocomial infections in the Inner Mongolia Autonomous Region of China [2012-2014]. AB - BACKGROUND: To investigate the prevalence of nosocomial infections, the distribution of nosocomial infection sites, the use of antibiotic and the situation of detected nosocomial infection pathogens in the Inner Mongolia Autonomous Region of China from 2012 to 2014, to grasp the current conditions of regional nosocomial infections in timely, for the development of infection prevention and control measures to provide a basis for effective hospital. METHODS: A survey of the prevalence of nosocomial infections was conducted in target hospitals using the combination of a bedside survey and medical record review. RESULTS: In total, 101,907 inpatients were surveyed from 2012 to 2014. There were 1,997 cases of nosocomial infections, accounting for an average prevalence of 1.96%. The infection site was mainly the lower respiratory tract. Higher prevalence of nosocomial infections occurred in the comprehensive intensive care unit (ICU), Neurosurgery Department, and Hematology Department. The average rate of antibiotic use was 33.72%, and the average submission rate for bacterial cultures for patients who received therapeutic treatment with antibiotics was 28.26%. The most common pathogens associated with nosocomial infections were Gram-negative (G(-)) bacteria, and frequently detected bacterial pathogens included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. CONCLUSIONS: The survey of the prevalence of nosocomial infections helped to identify problems in the control process of nosocomial infections and to develop targeted measures for the prevention and control of these infections accordingly. PMID- 26543615 TI - Chronic Klebsiella pneumonia: a rare manifestation of Klebsiella pneumonia. AB - K. pneumoniae can present as two forms of community-acquired pneumonia, acute and chronic. Although acute pneumonia may turn into necrotizing pneumonia, which results in a prolonged clinical course, it often has a rapidly progressive clinical course. In contrast, chronic Klebsiella pneumonia runs a protracted indolent course that mimics other chronic pulmonary infections and malignancies. Herein, we present two cases of chronic Klebsiella pneumonia. The diagnosis was made by microorganism identification, as well as absence of other potential causes. Clinical and radiographic findings improved after a prolonged course of antibiotic therapy. PMID- 26543616 TI - A rare long-term survival of the life-threatening trio: silent myocardial infarction complicated by ventricular septal rupture, type 2 diabetes mellitus and chronic bronchitis. AB - Silent myocardial infarction followed by ventricular septal rupture (VSR) is a rare phenomenon. In the absence of a timely diagnosis and surgical correction, the short term mortality of such patients is greater than 90%. We present one such unique case of a patient with an asymptomatic myocardial infarction complicated by VSR, type 2 diabetes mellitus and chronic bronchitis. Unfortunately, this possibly life-threatening condition had been misdiagnosed for more than one month after initial medical contact. Lack of typical symptoms of chest pain and chronic bronchitis is primarily responsible for this long-time misdiagnosis. We want to emphasize the importance of systematic diagnostic work up, high vigilance for possibility of VSR complicating myocardial infarction in aged patients with diabetes and chronic bronchitis, which may mislead doctors' judgments and put patients at high risk. PMID- 26543617 TI - Minimally invasive is the future of left ventricular assist device implantation. AB - There have been many factors that have allowed for progressive improvement in outcomes and lower complication rates. These include the improvement in left ventricular assist device (LVAD) technologies, combined with better understanding of patient management, all these. Nowadays the numbers of LVAD implantations exceed the number of annual heart transplants worldwide. Minimally invasive procedures are shown to improve the surgical outcome in both LVAD insertion and replacement. These minimally invasive techniques can be grouped grossly into shifting from on-pump to off-pump implantation, alternative access for implantation other than sternotomy, and a combination of both, which should be the ultimate aim of minimally invasive LVAD implantation. Here we describe the alternative techniques and configurations of minimally invasive and sites of implantation. PMID- 26543618 TI - Convex probe endobronchial ultrasound: applications beyond conventional indications. AB - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is maturing and gaining acceptance by more and more clinicians for lymph node staging of lung cancer and diagnosis of mediastinal and hilar masses or lymph node enlargement by convex probe endobronchial ultrasound (CP-EBUS). The application of CP-EBUS, however, is not limited to conventional indications. Diagnostically, elastography is a new technology for the differentiation of benign and malignant lymph nodes before aspiration. CP-EBUS can also be used for pulmonary vascular diseases, such as pulmonary embolism (PE) and non-thrombotic endovascular lesions (NELs). Therapeutically, CP-EBUS can be used for cyst drainage and drug injections. CP-EBUS is not limited to observation and aspiration of mediastinal masses and lymph nodes, but is also suitable for exploration of other tissues external to the central airway, which necessitates unprecedented skills for the bronchoscopist. PMID- 26543619 TI - Clinical manifestations of sleep apnea. AB - Obstructive sleep apnea (OSA) may manifest in a number of ways from subtle intrusion into daily life to profound sleepiness, snoring, witnessed apneas and other classic symptoms. Although there is increasing evidence suggesting OSA can adversely affect health in a variety of ways, this disorder remains underdiagnosed. The most well-escribed health consequences of OSA relate to the cardiovascular system. Hypertension and arrhythmias have a strong association with OSA, and evidence suggests that treatment of OSA in patients with refractory hypertension and in patients planning cardioversion for atrial fibrillation may be of particularly importance. Significant associations between heart failure and OSA as well as complex sleep apnea have also been well-described. Cerebrovascular insult, impaired neurocognition, and poorly controlled mood disorder are also associated with in OSA. Therapy for OSA may ameliorate atherosclerotic progression and improve outcomes post-cerebrovascular accident (CVA). OSA should be considered in patients complaining of poor concentration at work, actual or near-miss motor vehicle accidents, and patients with severe sleepiness as a component of their co-morbid mood disorders. The metabolic impact of OSA has also been studied, particularly in relation to glucose homeostasis. Also of interest is the potential impact OSA has on lipid metabolism. The adverse effect untreated OSA has on glucose tolerance and lipid levels has led to the suggestion that OSA is yet another constituent of the metabolic syndrome. Some of these metabolic derangements may be related to the adverse effects untreated OSA has on hepatic health. The cardiovascular, neurocognitive, and metabolic manifestations of OSA can have a significant impact on patient health and quality of life. In many instances, evidence exists that therapy not only improves outcomes in general, but also modifies the severity of co-morbid disease. To mitigate the long-term sequela of this disease, providers should be aware of the subtle manifestations of OSA and order appropriate testing as necessary. PMID- 26543622 TI - Editorial comment on: "Major morbidity after video-assisted thoracic surgery lung resections: a comparison between the European Society of Thoracic Surgeons definition and the Thoracic Morbidity and Mortality system" by Sandri A, et al. PMID- 26543621 TI - Growth of pure ground-glass lung nodule detected at computed tomography. AB - The natural history of pure ground-glass nodules (GGNs) of the lung has been gradually revealed. Approximately 10-25% of pure GGNs increases in size or grow the solid component, while others remain unchanged for years. Further investigations including the relationship between the successive change on computed tomography (CT) and the molecular change may be necessary to determine the appropriate management strategy of pure GGNs. PMID- 26543620 TI - Ultrasound techniques in the evaluation of the mediastinum, part I: endoscopic ultrasound (EUS), endobronchial ultrasound (EBUS) and transcutaneous mediastinal ultrasound (TMUS), introduction into ultrasound techniques. AB - Ultrasound imaging has gained importance in pulmonary medicine over the last decades including conventional transcutaneous ultrasound (TUS), endoscopic ultrasound (EUS), and endobronchial ultrasound (EBUS). Mediastinal lymph node staging affects the management of patients with both operable and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography (EUS and EBUS) should be the initial tissue sampling test over surgical staging. Mediastinal nodes can be sampled from the airways [EBUS combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [EUS fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all mediastinal lymph nodes can be biopsied. Additionally endosonography has an excellent yield in assessing granulomas in patients suspected of sarcoidosis. The aim of this review, in two integrative parts, is to discuss the current role and future perspectives of all ultrasound techniques available for the evaluation of mediastinal lymphadenopathy and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part I is dealing with an introduction into ultrasound techniques, mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques and part II with the clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography. PMID- 26543623 TI - Wave mice: a new tool in the quest to characterize aortic valvular disease etiologies. PMID- 26543624 TI - Editorial on the article entitled "Surgical ablation of atrial fibrillation during mitral-valve surgery". PMID- 26543625 TI - Lung cancer screening using low dose CT: screening population and positive results definition. PMID- 26543626 TI - Where are we on (preventing) pneumothorax after (cone-beam) computed tomography guided lung biopsy? PMID- 26543627 TI - The enigmatic esophageal anastomosis. PMID- 26543628 TI - Etomidate: to use or not to use for endotracheal intubation in the critically ill? AB - Endotracheal intubation is frequently performed in the intensive care unit (ICU). It can be life-saving for many patients who present with acute respiratory distress. However, it is equally associated with complications that may lead to unwanted effects in this patient population. According to the literature, the rate of complications associated with endotracheal intubation is much higher in an environment such as the ICU as compared to other, more controlled environments (i.e., operating room). Thus, the conduct of performing such a procedure needs to be accomplished with the utmost care. To facilitate establishment of the breathing tube, sedation is routinely administered. Given the tenuous hemodynamic status of the critically ill, etomidate was frequently chosen to blunt further decreases in blood pressure and/or heart rate. Recently however, reports have demonstrated a possible association with the use of etomidate for endotracheal intubation and mortality in the critically ill. In addition, this association seems to be predominantly in patients diagnosed with sepsis. As a result, some have advocated against the use of this medication in septic patients. Due to the negative associations identified with etomidate and mortality, several investigators have evaluated potential alternatives to this solution (e.g., ketamine and ketamine-propofol admixture). These studies have shown promise. However, despite the evidence against using etomidate for endotracheal intubation, other studies have demonstrated no such association. This leaves the critical care clinician with uncertainty regarding the best sedative to administer in this patient population. The following editorial discusses current evidence regarding etomidate use for endotracheal intubation and mortality. In particular, we highlight a recent article with the largest population to date that found no association between etomidate and mortality in the critically ill and illustrate important findings that the reader should be aware of regarding this article. PMID- 26543629 TI - Is the rapid needle-out patient-rollover approach after CT-guided lung biopsy really effective for pneumothorax prevention? PMID- 26543630 TI - The multidrug-resistant tuberculosis threat: old problems and new solutions. PMID- 26543631 TI - Uniportal video assisted thoracic surgery: summary of experience, mini-review and perspectives. AB - The uniportal-video assisted thoracic surgery (VATS) technique comprises operations which can be performed with skin incisions ranging from 2 to 8 cm and the manifest result of the introduction of the uniportal lobectomy had made possible to increase rapidly the number of published papers on this subject. Many of the large ensuing literature report incomplete historical information on uniportal VATS, and doubts exist about the indication of uniportal VATS for some thoracic oncologic pathologies. Known limitations have been overcome. On the other hand, the modern thoracic surgical team includes one surgeon, one assistant and a scrub nurse, and it is clear that the new generation of thoracic surgeons need to use the "less" used hand. The new technology which permitted the introduction of the uniportal VATS could influence the future need of thoracic surgeons worldwide. PMID- 26543632 TI - Indicator or continuous variable? PMID- 26543633 TI - Professor Hyun Koo Kim: a great master of single port video-assisted thoracoscopic surgery. PMID- 26543634 TI - The world's first radical resection for lung cancer using glasses-free 3D thoracoscope was completed in Guangzhou. PMID- 26543635 TI - The highlights in the 23(rd) Annual Meeting of the Asian Society for Cardiovascular and the Thoracic Surgery. PMID- 26543636 TI - The 6(th) Zhongshan minimal invasive thoracic surgery and endoscope symposium was successfully held. PMID- 26543637 TI - Erratum to video-assisted thoracoscopic surgery right upper posterior segmentectomywith systemic mediastinal lymph node dissection. AB - [This corrects the article on p. 1819 in vol. 6, PMID: 25589980.]. PMID- 26543638 TI - Erratum to accidental invisible intrathoracic disseminated pT4-M1a: a distinct lung cancer with favorable prognosis. AB - [This corrects the article on p. 1205 in vol. 7.]. PMID- 26543639 TI - The Challenge of Parenting Girls in Neighborhoods of Different Perceived Quality. AB - It is well-known that disadvantaged neighborhoods, as officially identified through census data, harbor higher numbers of delinquent individuals than advantaged neighborhoods. What is much less known is whether parents' perception of the neighborhood problems predicts low parental engagement with their girls and, ultimately, how this is related to girls' delinquency, including violence. This paper elucidates these issues by examining data from the Pittsburgh Girls Study, including parent-report of neighborhood problems and level of parental engagement and official records and girl-reported delinquency at ages 15, 16, and 17. Results showed higher stability over time for neighborhood problems and parental engagement than girls' delinquency. Parents' perception of their neighborhood affected the extent to which parents engaged in their girls' lives, but low parental engagement did not predict girls being charged for offending at age 15, 16 or 17. These results were largely replicated for girls' self-reported delinquency with the exception that low parental engagement at age 16 was predictive of the frequency of girls' self-reported delinquency at age 17 as well. The results, because of their implications for screening and early interventions, are relevant to policy makers as well as practitioners. PMID- 26543640 TI - Correlation of Prehypertension with Left Ventricular Mass Assessed by Cardiac Magnetic Resonance Imaging. AB - Introduction. The purpose of this observational cross-sectional study was to assess left ventricular mass (LVM) in prehypertensive individuals in comparison to normotensives and to determine if central blood pressure (BP) correlates better with LVM index (LVMI) than brachial BP. Methods and Result. Brachial and central BP measurements were completed at first visit and at 4 weeks in 65 healthy volunteers who were at least 40 years old and not on medication. Subjects were divided into two groups of normotensives and prehypertensives based on JNC-7 criteria and LVM was obtained using cardiac magnetic resonance imaging. Prehypertensives had significantly higher LVMI compared to normotensives (P < 0.01). Brachial and central BP also both positively correlate with LVMI (r = 0.460, P < 0.01; r = 0.318, P = 0.012, resp.) in both groups and neither method was superior to the other. After multivariate regression analysis and adjusting for cardiovascular risk factors, prehypertension remained an independent determinant of LVM. Conclusion. Prehypertension is associated with cardiovascular target organ damage, and central BP was not superior to brachial BP or vice versa for association with LVMI. PMID- 26543641 TI - Comment on "Modulation of Metabolic Detoxification Pathways Using Foods and Food Derived Components: A Scientific Review with Clinical Application". PMID- 26543642 TI - Optimal Use of Plant Stanol Ester in the Management of Hypercholesterolemia. AB - Plant stanol ester is a natural compound which is used as a cholesterol-lowering ingredient in functional foods and food supplements. The safety and efficacy of plant stanol ester have been confirmed in more than 70 published clinical studies and the ingredient is a well-established and widely recommended dietary measure to reduce serum cholesterol. Daily intake of 2 g plant stanols as plant stanol ester lowers LDL-cholesterol by 10%, on average. In Europe, foods with added plant stanol ester have been on the market for 20 years, and today such products are also available in many Asian and American countries. Despite the well documented efficacy, the full potential in cholesterol reduction may not be reached if plant stanol ester is not used according to recommendations. This review therefore concentrates on the optimal use of plant stanol ester as part of dietary management of hypercholesterolemia. For optimal cholesterol lowering aiming at a lower risk of cardiovascular disease, plant stanol ester should be used daily, in sufficient amounts, with a meal and in combination with other recommended dietary changes. PMID- 26543643 TI - Nurses' and Nursing Students' Knowledge and Attitudes regarding Pediatric Pain. AB - Nursing staff spend more time with patients with pain than any other health staff member. For this reason, the nurse must possess the basic knowledge to identify the presence of pain in patients, to measure its intensity and make the steps necessary for treatment. Therefore, a prospective, descriptive, analytical, and cross-sectional study was conducted to investigate the knowledge and attitudes regarding pediatric pain in two different populations. The questionnaire, Pediatric Nurses Knowledge and Attitudes Survey Regarding Pain (PKNAS), was applied to 111 hospital pediatric nurses and 300 university nursing students. The final scores for pediatric nurses and nursing students were 40.1 +/- 7.9 and 40.3 +/- 7.5, respectively. None of the sociodemographic variables predicted the scores obtained by the participants (P > 0.05). There was a high correlation between the PKNAS scores of pediatric nurses and nursing students (r = 0.86, P < 0.001). It was observed that the degree of knowledge about pain and its treatment was very low in both groups. Due to this deficiency, pain in children remains inadequately managed, which leads to suffering in this population. It is necessary to increase the continued training in this subject in both areas. PMID- 26543644 TI - Clinical Use of Anti-Xa Monitoring in Malignancy-Associated Thrombosis. AB - Introduction. Low molecular weight heparin (LMWH) is preferred for malignancy associated venous thromboembolism (VTE). Many providers monitor LMWH with anti-Xa levels, despite little validation on correspondence with patient outcome. Methods. This is a retrospective, single institution study of anti-Xa measurement in malignancy-associated thrombosis. Cases were identified using the Electronic Data Warehouse, and inclusion was confirmed by two independent reviewers. Malignancy type, thrombotic history, measurement rationale and accuracy, clinical context, and management changes were evaluated. Results. 167 cases met inclusion criteria. There was no clear rationale for anti-Xa testing in 56%. Impaired renal function (10%), documented or suspected recurrent thrombosis despite anticoagulation (9%), and bleeding (6%) were the most common reasons for testing. Incorrect measurement occurred in 44%. Renal impairment was not a significant impetus for testing, as 70% had a GFR > 60. BMI > 30 was present in 40%, and 28% had a BMI < 25. Clinical impact was low, as only 11% of patients had management changes. Conclusions. Provider education in accuracy and rationale for anti-Xa testing is needed. Our study illustrates uncertainty of interpretation and clinical impact of routine anti-Xa testing, as management was affected in few patients. It is not yet clear in which clinical context providers should send anti-Xa levels. PMID- 26543645 TI - Intravenous Dexmedetomidine Provides Superior Patient Comfort and Tolerance Compared to Intravenous Midazolam in Patients Undergoing Flexible Bronchoscopy. AB - Dexmedetomidine, an alpha2 agonist, has demonstrated its effectiveness as a sedative during awake intubation, but its utility in fiberoptic bronchoscopy (FOB) is not clear. We evaluated the effects of midazolam and dexmedetomidine on patient's response to FOB. The patients received either midazolam, 0.02 mg/kg (group M, n=27), or dexmedetomidine, 1 ug/kg (group D, n=27). A composite score of five different parameters and a numerical rating scale (NRS) for pain intensity and distress were used to assess patient response during FOB. Patients rated the quality of sedation and level of discomfort 24 h after the procedure. Ease of bronchoscopy, rescue medication requirement, and haemodynamic variables were noted. Ideal or acceptable composite score was observed in 15 and 26 patients, respectively, in group M (14.48+/-3.65) and group D (9.41+/-3.13), p<0.001. NRS showed that 11 patients in group M had severe pain and discomfort as compared to one patient with severe pain and two with severe discomfort in group D during the procedure, p<0.001. Rescue midazolam requirement was significantly higher in group M (p=0.023). We conclude that during FOB, under topical airway anaesthesia, IV dexmedetomidine (1 ug/kg) provides superior patient comfort and tolerance as compared to IV midazolam (0.02 mg/kg). PMID- 26543646 TI - The Effects of Simvastatin on Proteinuria and Renal Function in Patients with Chronic Kidney Disease. AB - Current data suggests that statins might have beneficial effects on renal outcomes. Beneficial effects of statin treatment on renal progression in advanced chronic kidney disease (CKD) are obviously controversial. In a retrospective, controlled study, the authors have evaluated the effects of 53-week treatment with simvastatin, versus no treatment on proteinuria and renal function among 51 patients with CKD stages III-IV. By the end of the 53-week treatment, urine protein excretion decreased from 0.96 (IQR 0.54, 2.9) to 0.48 (IQR 0.18, 0.79) g/g creatinine (P < 0.001) in patients treated with simvastatin in addition to ACEI and ARBs, while no change was observed among the untreated patients. Moreover, a significantly greater decrease in urine protein excretion was observed in the simvastatin group as compared with the untreated group. The mean changes of serum creatinine and eGFR did not significantly differ in both groups. A significantly greater decrease in total cholesterol and LDL-cholesterol was found in the simvastatin group than in the untreated group. In summary, apart from lipid lowering among CKD patients, ingesting simvastatin was associated with a decrease in proteinuria. These statin effects may become important for supportive therapy in renal damage in the future. PMID- 26543647 TI - Exploring Innovative Solutions for Quality of Life and Care of Bed-Ridden Nursing Home Residents through Codesign Sessions. AB - Bed-ridden nursing home residents are in need of environments which are homelike and facilitate the provision of care. Design guidance for this group of older people is limited. This study concerned the exploration and generation of innovative environmental enrichment scenarios for bed-ridden residents. This exploration was conducted through a combination of participatory action research with user-centred design involving 56 professional stakeholders in interactive work sessions. This study identified numerous design solutions, both concepts and products that are available on the marketplace and that on a higher level relate to improvements in resident autonomy and the supply of technological items and architectural features. The methodology chosen can be used to explore the creative potential of stakeholders from the domain of healthcare in product innovation. PMID- 26543649 TI - Psychosocial Predictors for Cancer Prevention Behaviors in Workplace Using Protection Motivation Theory. AB - Backgrounds. The aim of this study was to describe the preventive behaviors of industrial workers and factors influencing occupational cancer prevention behaviors using protection motivation theory. Methods. A self-administered questionnaire was completed by 161 petrochemical workers in Iran in 2014 which consisted of three sections: background information, protection motivation theory measures, and occupational cancers preventive behaviors. Results. A statistically significant positive correlation was found between PM and self-efficacy, response efficacy, and the cancer preventive behaviors. Meanwhile, statistically significant negative correlations were found between PM, cost, and reward. Conclusions. Among available PMT constructs, only self-efficacy and cost were significant predictors of preventive behaviors. Protection motivation model based health promotion interventions with focus on self-efficacy and cost would be desirable in the case of occupational cancers prevention. PMID- 26543648 TI - Comparison of the Explantation Rate of Poly Implant Prothese, Allergan, and Perouse Silicone Breast Implants within the First Four Years after Reconstructive Surgery before the Poly Implant Prothese Alert by the French Regulatory Authority. AB - Background. In March 2010, ANSM (Agence Nationale de Securite du Medicament), the French Medical Regulatory Authority, withdrew Poly Implant Prothese (PIP) breast implants from the market due to the use of non-medical-grade silicone gel. The aim of this study was to compare the removal rate (and reasons thereof) of breast implants produced by different manufacturers before the ANSM alert. Materials and Methods. From October 2006 to January 2010, 652 women received 944 implants after breast cancer surgery at the Gustave Roussy Comprehensive Cancer Center, Paris (France). The complications and removal rates of the different implant brands used (PIP, Allergan, and Perouse) were evaluated and compared. Results. PIP implants represented 50.6% of the used implants, Allergan 33.4%, and Perouse 16%. The main reasons for implant removal were patient dissatisfaction due to aesthetic problems (43.2%), infection (22.2%), and capsular contracture (13.6%). Two years after implantation, 82% of Perouse implants, 79% of PIP, and 79% of Allergan were still in situ. There was no difference in removal rate among implant brands. Conclusion. Before the ANSM alert concerning the higher rupture rate of PIP breast implants, our implant removal rate did not predict PIP implant failure related to the use of nonapproved silicone gel. PMID- 26543650 TI - A Rare Case of Complete Stent Fracture, Coronary Arterial Transection, and Pseudoaneurysm Formation Induced by Repeated Stenting. AB - This report describes a rare asymptomatic case of complete stent fracture, coronary arterial transection, and pseudoaneurysm formation in response to repeated stenting. The proximal and distal ends of transected coronary artery were closed, and distal bypass was performed. Coronary arterial transection can occur in patients with repeated stenting as a long-term adverse event. PMID- 26543651 TI - Comment on "Takotsubo Cardiomyopathy: A New Perspective in Asthma". PMID- 26543652 TI - Acetabular Liner Dissociation following Total Hip Arthroplasty: A Rare but Serious Complication That May Be Easily Misinterpreted in the Emergency Department. AB - Acetabular liner dissociation is a rare complication of Total Hip Arthroplasty (THA) which requires urgent revision surgery. A case is presented in which the correct diagnosis was not appreciated on two separate Emergency Department attendances. The typical symptoms, signs, and radiological features are outlined and the importance of considering a rare complication following a commonly performed procedure is highlighted. PMID- 26543653 TI - Progressive Lower Extremity Weakness and Axonal Sensorimotor Polyneuropathy from a Mutation in KIF5A (c.611G>A;p.Arg204Gln). AB - Introduction. Hereditary Spastic Paraplegia (HSP) is a rare hereditary disorder that primarily involves progressive spasticity of the legs (hamstrings, quadriceps, and calves). Methods. A 27-year-old gentleman was a fast runner and able to play soccer until age 9 when he developed slowly progressive weakness. He was wheelchair-bound by age 25. He was evaluated by laboratory testing, imaging, electrodiagnostics, and molecular genetics. Results. Electrodiagnostic testing revealed an axonal sensorimotor polyneuropathy. Genetic testing for HSP in 2003 was negative; repeat testing in 2013 revealed a mutation in KIF5A (c.611G>A;p.Arg204Gln). Conclusions. A recent advance in neurogenetics has allowed for more genes and mutations to be identified; over 76 different genetic loci for HSP and 59 gene products are currently known. Even though our patient had a sensorimotor polyneuropathy on electrodiagnostic testing and a 2003 HSP genetic panel that was negative, a repeat HSP genetic panel was performed in 2013 due to the advancement in neurogenetics. This revealed a mutation in KIF5A. PMID- 26543654 TI - Rivaroxaban-Induced Nontraumatic Spinal Subdural Hematoma: An Uncommon Yet Life Threatening Complication. AB - In the last decade, the desire for safer oral anticoagulants (OACs) led to the emergence of newer drugs. Available clinical trials demonstrated a lower risk of OACs-associated life-threatening bleeding events, including intracranial hemorrhage, compared to warfarin. Nontraumatic spinal hematoma is an uncommon yet life-threatening neurosurgical emergency that can be associated with the use of these agents. Rivaroxaban, one of the newly approved OACs, is a direct factor Xa inhibitor. To the best of our knowledge, to date, only two published cases report the incidence of rivaroxaban-induced nontraumatic spinal subdural hematoma (SSDH). Our case is the third one described and the first one to involve the cervicothoracic spine. PMID- 26543655 TI - Peripapillary Intrachoroidal Cavitation in Myopia Evaluated with Multimodal Imaging Comprising "En-Face" Technique. AB - Objectives. To demonstrate the usefulness of "en-face" Spectral Domain Optical Coherence Tomography (SD-OCT) combined with Fluorescein Angiography (FA) in the investigation of peripapillary intrachoroidal cavitation. Materials and Methods. A 72-year-old man followed for primary open-angle glaucoma (POAG) for 4 years was referred for an asymptomatic "peripapillary lesion." A full ophthalmological examination and conventional imaging of the retina were done. FA, Indocyanine Green Angiography (ICG-A), and SD-OCT using the "en-face" technique were also performed. Results. Best-corrected visual acuity (BCVA) was 20/25 both eyes. Slit lamp examination revealed no abnormalities of anterior segment. Intraocular pressure (IOP) was normal. Fundus examination showed a triangular yellow-orange thickening at the inferior border of both optic nerves. FA showed early hypofluorescence of the lesion and progressive staining without any dye pooling. SD-OCT with "en-face" technique showed an intrachoroidal hyporeflective space resembling a cavitation below the retinal pigment epithelium (RPE). Conclusions. "En-face" SD-OCT and FA are valuable techniques for the diagnosis of peripapillary intrachoroidal cavitation associated with myopia. Pathophysiological insights regarding SD-OCT findings and angiography behavior are offered. PMID- 26543657 TI - Patellofemoral Joint Replacement and Nickel Allergy: An Unusual Presentation. AB - Metal allergy is an unusual complication of joint replacement that may cause aseptic loosening and necessitate joint revision surgery. We present the case of nickel allergy causing aseptic loosening following patellofemoral joint replacement (PFJR) in a 54-year-old male. Joint revision surgery to a nickel-free total knee replacement was performed with good results. Our literature review shows that there is no evidence to guide the management of metal allergy in PFJR. The evidence from studies of total knee replacement is limited to retrospective case series and case reports and gives contradictory recommendations. The optimal management strategy for metal allergy in PFJR is not clear. We recommend allergy testing in patients with history of metal allergy and use of an allergen-free implant in those with positive tests. As there is no gold standard test to establish metal allergy, the choice of test should be guided by availability and recommendation from the local unit of dermatology and allergy testing. We recommend investigation for metal allergy in patients with implant loosening where other causes have been excluded. PMID- 26543656 TI - Occipital Condyle Fracture with Accompanying Meningeal Spinal Cysts as a result of Cervical Spine Injury in 15-Year-Old Girl. AB - The occipital condyle fracture is rare injury of the craniocervical junction. Meningeal spinal cysts are rare tumors of the spinal cord. Depending on location, these lesions may be classified as extradural and subdural, but extradural spinal cysts are more common. We present the case of a 15-year-old girl who suffered from avulsion occipital condyle fracture treated with use of "halo-vest" system. We established that clinical effect after completed treatment is very good. Control MRI evaluation was performed 12 months after removal of "halo-vest" traction, and clinically silent extradural meningeal spinal cysts were detected at the ventral side of the spinal cord in the cervical segment of the spine. Due to clinically silent course of the disease, we decided to use the conservative treatment. The patient remains under control of our department. PMID- 26543658 TI - A Bizarre, Unexplained, and Progressive External Rotation of the Shoulder as a Presentation of a Metastatic Deposit in the Rotator Cuff. AB - We describe the first reported case of a tumour deposit within the rotator cuff presenting as a bizarre, progressive, and fixed external rotation deformity of the shoulder. It is also the first reported case to our knowledge of an oesophageal primary metastasising to the rotator cuff. PMID- 26543659 TI - Gastrojejunal Anastomosis Perforation after Gastric Bypass on a Patient with Underlying Pancreatic Cancer: A Case Report and Review of the Literature. AB - Introduction. We describe a case of gastrojejunal anastomosis perforation after gastric bypass on a patient with underlying pancreatic cancer. Case Description. A 54-year-old female with past surgical history of gastric bypass for morbid obesity and recent diagnosis of unresectable pancreatic cancer presents with abdominal pain, peritonitis, and sepsis. Computerized axial tomography scan shows large amount of intraperitoneal free air. The gastric remnant is markedly distended and a large pancreatic head mass is seen. Intraoperative findings were consistent with a perforated ulcer located at the gastrojejunal anastomosis and a distended gastric remnant caused by a pancreatic mass invading and obstructing the second portion of the duodenum. The gastrojejunal perforation was repaired using an omental patch. A gastrostomy for decompression of the remnant was also performed. The patient had a satisfactory postoperative period and was discharged on day 7. Discussion. Perforation of the gastrojejunal anastomosis after Roux-en Y gastric bypass is an unusual complication. There is no correlation between the perforation and the presence of pancreatic cancer. They represent two different conditions that coexisted. The presence of a gastrojejunal perforation made the surgeon aware of the advanced stage of the pancreatic cancer. PMID- 26543660 TI - Splenosis: A Rare Etiology for Bowel Obstruction-A Case Report and Review of the Literature. AB - Splenosis is a historically uncommon etiology for bowel obstruction. Autotransplanted splenic tissues following surgery or trauma of the spleen are known to occur in multiple locations of the abdominal cavity and pelvis. The small bowel mesentery is a blood vessel-rich environment for growth of splenic fragments. We present a case of a 36-year-old male patient who sustained a gunshot wound to his left abdomen requiring a splenectomy and bowel resection fifteen years prior to his presentation with small bowel obstruction requiring exploration, adhesiolysis, and resection of the mesenteric splenic deposit. Our aim in this report is to provide awareness of splenosis as an etiology for bowel obstruction, especially with increased incidence and survival following abdominal traumas requiring splenectomies. We also stress on the importance of history and physical examination to include splenosis on the list of differential diagnoses for bowel obstruction. PMID- 26543661 TI - The Localization and Characterization of Ischemic Scars in relation to the Infarct Related Coronary Artery Assessed by Cardiac Magnetic Resonance and a Novel Automatic Postprocessing Method. AB - Aims. The correspondence between the localization and morphology of ischemic scars and the infarct related artery (IRA) by use of cardiac magnetic resonance imaging and a novel automatic postprocessing method. Methods and Results. Thirty four patients with one-year-old single IRA myocardial infarction were examined. Endocardium, epicardium, and the point where right and left ventricles are coinciding were manually marked. All measurements were automatically assessed by the method. The following are results with manual assessments of scar properties in parenthesis: mean scar size (FWHM criterion): 7.8 +/- 5.5 as %LV (17.4 +/- 8.6%); mean endocardial extent of infarction: 44 +/- 26 degrees (124 +/- 47 degrees ); mean endocardial extent of infarction as %LV circumference: 9.7 +/- 7.0% (34.6 +/- 13.0%); and mean transmurality: 52 +/- 20% of LV wall thickness (77 +/- 23%). Scars located in segments 1, 2, 7, 8, 13, and 14 by use of the automatic method were 96-100% specific for LAD occlusion. The highest specificities of RCA and LCX occlusions were segment 4 with 93% and segment 6 with 64%, respectively. The scar localization assessed automatically or manually was without major differences. Conclusion. The automatic method is applicable and able to assess localization, size, transmurality, and endocardial extent of ischemic scars. PMID- 26543662 TI - Population-Based Seroprevalence of Malaria in Hormozgan Province, Southeastern Iran: A Low Transmission Area. AB - The seroepidemiological condition of malaria in three main districts of Hormozgan Province, a low transmission area in southeast of Iran, was investigated. Methods. Sera samples (803) were collected from healthy volunteers from the three main districts (Bandar Lengeh in the west, Bandar Abbas in the center, and Bandar Jask in the east) of Hormozgan Province. A questionnaire was used to record the sociodemographic features of the participants during sample collecting. An in house ELISA test, using crude antigens obtained from cell culture of Plasmodium falciparum, was adapted and used to detect anti-malaria antibodies in the sera. Results. The overall seroprevalence of malaria was 8.7% (70 out of 803 samples). A significant correlation was found between seropositivity and place of residence, where the highest rate of seropositivity was seen in Bandar Lengeh (west of the province). The highest seroprevalence of malaria (13.2%) was seen in the age group of 11-20 years and also in low educated individuals. Correlation between seropositivity and gender, age, and educational levels of the participants was statistically significant (P < 0.05). Conclusion. Findings of this study indicate that the rate of seropositivity to malaria in this area is not high and this might be linked to the success of malaria control programs during the last decades in the region. PMID- 26543663 TI - Assessment of Nonverbal and Verbal Apraxia in Patients with Parkinson's Disease. AB - Objective. To assess the presence of nonverbal and verbal apraxia in patients with Parkinson's disease (PD) and analyze the correlation between these conditions and patient age, education, duration of disease, and PD stage, as well as evaluate the correlation between the two types of apraxia and the frequency and types of verbal apraxic errors made by patients in the sample. Method. This was an observational prevalence study. The sample comprised 45 patients with PD seen at the Movement Disorders Clinic of the Clinical Hospital of Porto Alegre, Brazil. Patients were evaluated using the Speech Apraxia Assessment Protocol and PD stages were classified according to the Hoehn and Yahr scale. Results. The rate of nonverbal apraxia and verbal apraxia in the present sample was 24.4%. Verbal apraxia was significantly correlated with education (p <= 0.05). The most frequent types of verbal apraxic errors were omissions (70.8%). The analysis of manner and place of articulation showed that most errors occurred during the production of trill (57.7%) and dentoalveolar (92%) phonemes, consecutively. Conclusion. Patients with PD presented nonverbal and verbal apraxia and made several verbal apraxic errors. Verbal apraxia was correlated with education levels. PMID- 26543664 TI - The Effect of Telemedicine on Access to Acute Stroke Care in Texas: The Story of Age Inequalities. AB - Background. Ischemic stroke is a time sensitive disease with the effectiveness of treatment decreasing over time. Treatment is more likely to occur at Primary Stroke Centers (PSC); thus rapid access to acute stroke care through stand-alone PSCs or telemedicine (TM) is vital for all Americans. The objective of this study is to determine if disparities exist in access to PSCs or the extended access to acute stroke care provided by TM. Methods. Data from the US Census Bureau and the 2010 Neilson Claritas Demographic Estimation Program, American Hospital Association annual survey, and The Joint Commission list of PSCs and survey response data for all hospitals in the state of Texas were used. Results. Over 64% of block groups had 60-minute ground access to acute stroke care. The odds of a block group having 60-minute access to acute stroke care decreased with age, despite adjustment for sex, race, ethnicity, socioeconomic status, urbanization, and total population. Conclusion. Our survey of Texas hospitals found that as the median age of a block group increased, the odds of having access to acute stroke care decreased. PMID- 26543665 TI - New Sample Preparation Method for Quantification of Phenolic Compounds of Tea (Camellia sinensis L. Kuntze): A Polyphenol Rich Plant. AB - Chemical analysis of the Sri Lankan tea (Camellia sinensis, L.) germplasm would immensely contribute to the success of the tea breeding programme. However, the polyphenols, particularly catechins (flavan-3-ols), are readily prone to oxidation in the conventional method of sample preparation. Therefore, optimization of the present sample preparation methodology for the profiling of metabolites is much important. Two sample preparation methodologies were compared, fresh leaves (as in the conventional procedures) and freeze-dried leaves (a new procedure), for quantification of major metabolites by employing two cultivars, one is known to be high quality black tea and the other low quality black tea. The amounts of major metabolites such as catechins, caffeine, gallic acid, and theobromine, recorded in the new sampling procedure via freeze dried leaves, were significantly higher than those recorded in the conventional sample preparation procedure. Additionally new method required less amount of leaf sample for analysis of major metabolites and facilitates storage of samples until analysis. The freeze-dried method would be useful for high throughput analysis of large number of samples in shorter period without chemical deterioration starting from the point of harvest until usage. Hence, this method is more suitable for metabolite profiling of tea as well as other phenol rich plants. PMID- 26543667 TI - CD8+ cytotoxic T lymphocytes in human influenza virus infection. PMID- 26543666 TI - Novel applications of statins for bone regeneration. AB - The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID- 26543669 TI - Study of factors determining caregiver burden among primary caregivers of patients with intracranial tumors. AB - BACKGROUND: Caregivers of patients with intracranial tumors handle physical, cognitive, and behavioral impairments of patients. The purpose of this study was to assess the magnitude of burden experienced by primary caregivers of patients operated for intracranial tumors and evaluate factors influencing it. METHODS: Descriptive cross-sectional design was used to assess home-care burden experienced by primary caregivers of patients operated for intracranial tumors. Using purposive sampling, 70 patient-caregiver pairs were enrolled. Modified caregiver strain index (MCSI) was used to assess the caregiver burden. Mini mental status examination (MMSE), Katz index of independence in activities of daily living (ADL), and neuropsychiatric inventory questionnaire (NPI-Q) were used to assess the status of patients. RESULTS: Of 70 caregivers, 45 had mild, and 22 had moderate MCSI burden. A number of behavioral changes in NPI-Q had a significant correlation with MCSI burden (P < 0.001), whereas MMSE and Katz-ADL of patients did not show significant relation with caregiver burden. In NPI-Q, irritability, agitation, anxiety, depression, and sleep disturbances had a significant impact on MCSI. Among caregiver factors, unemployment, low per capita income, time spent, inability to meet household needs, quitting the job, and health problems had a significant impact on MCSI. In separate multivariate analyses, irritability component (P = 0.004) among behavioral changes of patients and caregivers' inability to meet household needs (P < 0.001) had a significant association with caregiver burden independent of other factors. CONCLUSIONS: Behavioral changes in patients (especially irritability) and financial constraints had a significant independent impact on the burden experienced by primary caregivers of patients operated for intracranial tumors. Identifying and managing, these are essential for reducing caregiver burden. PMID- 26543670 TI - A case of a brain stem abscess with a favorable outcome. AB - BACKGROUND: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. CASE DESCRIPTION: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed tomography showed a space occupying lesion in the brain stem. She became shortly after comatose, and we decided to perform an acute stereotactic aspiration of the abscess. Soon after surgery, her neurological condition improved dramatically. CONCLUSION: A brainstem abscess is a life-threatening condition with a potentially good outcome if treated adequately. PMID- 26543668 TI - Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs. AB - Transposable elements (TEs) are mobile genomic sequences of DNA capable of autonomous and non-autonomous duplication. TEs have been highly successful, and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional, these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TE derived endogenous viral particles can even be detected. A similar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells (ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs (lncRNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lncRNAs, and how these links influence each other to modulate aspects of ESCs, embryogenesis, and somatic cell reprogramming. PMID- 26543671 TI - Long-term clinical and radiological follow-up after laminectomy for cervical spondylotic myelopathy. AB - BACKGROUND: The role of laminectomy in the surgical treatment of cervical spondylotic myelopathy (CSM) is established even though postoperative cervical sagittal balance changes and a risk for long-term instability have been described. The aim of the present study is to investigate its clinical efficacy and the radiological outcome in the long-term. METHODS: The authors retrospectively reviewed consecutive cases of patients with CSM, who underwent cervical laminectomy between 1995 and 2010 at the Hospital Sao Joao (n = 106). Clinical files were consulted, and the patients reassessed in order to collect information on complaints, previous neurological deficits, surgery and its complications. Subjective and objective clinical evaluation (by three myelopathy scores) and imaging studies were undertaken in order to assess the long-term cervical sagittal curvature and presence of instability. RESULTS: After applying exclusion criteria, 57 patients were able to complete the follow-up. A favorable statistically significant difference was obtained when comparing clinical scores. Ninety-one percent of patients were satisfied with the outcome of the surgery. Only 1 patient developed kyphosis according to Ishihara index and none according to the method of Matsumoto. Four patients developed subclinical cervical instability. No clinical-imaging correlation was found. CONCLUSIONS: If patients are properly selected cervical laminectomy without additional instrumentation is effective in offering a clinical improvement to patients with CSM with a low incidence of clinically significant radiological deterioration. PMID- 26543672 TI - Civility in scientific publishing: The glyphosate paper. AB - In recent years, we have witnessed a decline in civility in the public arena when various socially sensitive issues are being presented. Those of us engaged in the publishing of scientific papers and in our comments on these papers, need to be cognizant of the social graces, courteous demeanor, and chivalry. Debates are essential to our learning and in being able to ferret out the essentials of various scientific issues that are of value. Because of the amount of time and effort connected with analyzing the complex problems and the years invested in such endeavors, we often resort to the behavior, that is, contentious and at times even quite insulting to our opponents during our defense. This is the part of human nature but as civilized human beings, we must strive to maintain the courtesy and a calm demeanor during such discussions and debates. I have yielded to such temptations myself but am striving to repent of my sins. The medical and scientific history should have taught us that in defending our ideas we learn and sometimes come to the realization that our paradigm or hypothesis is wrong, either in part or whole. Such debates allow us to fine tune our ideas and correct our errors in thinking, which are easily, consciously, or subconsciously sublimated by our enthusiasm. The glyphosate papers presented ideas that, while well supported by the scientific studies and logical conclusions, also contained some possible errors in its suppositions. Dr. Miguel Faria challenged some of these concepts and was met with some degree of derision by one of the authors. This editorial comment is in response to these issues. PMID- 26543673 TI - Lumbopelvic parameters and the extent of lumbar fusion. AB - BACKGROUND: Following lumbar fusion, sacroiliac (SI) joint pain has been regarded as a form of adjacent segment disease. Prior studies suggest increased stress to the SI joint and pelvis with lumbar fusion. Limited studies have evaluated the relationship between the extent of lumbar fusion and its potential influence on lumbopelvic parameters, which may provide the insights to persistent back pain. METHODS: Three hundred fifty-five patients underwent lumbar fusions at our institution between fall 2010 and winter 2012; 80 patients met criteria for the study. Inclusion criteria included appropriate imaging available (preoperative and postoperative lateral films), follow-up >1-year, fusion where the rostral extent was up to L1 and the caudal extent was at most S1. Exclusion criteria included prior lumbar fusion, history of SI joint syndrome, follow-up <1-year, fusion involving thoracic levels, and inadequate films (inability to visualize appropriate anatomy). The patients were divided into groups based on the extent of fusion. The patients were evaluated based on age, sex, diagnosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. The preoperative values were compared among the groups, the postoperative values were compared among the groups, and the pre- and post-operative values were compared within each group. RESULTS: There were no statistically significant differences between pre- and post-operative lumbopelvic parameters within each fusion group. CONCLUSION: The results imply that the extent of instrumentation, including the involvement of the sacrum, may not alter lumbopelvic parameters. This appears to argue against the idea that longer fusion constructs induce more stress on the pelvis and SI joint. PMID- 26543674 TI - Validating the Use of Google Trends to Enhance Pertussis Surveillance in California. AB - INTRODUCTION AND METHODS: Pertussis has recently re-emerged in the United States. Timely surveillance is vital to estimate the burden of this disease accurately and to guide public health response. However, the surveillance of pertussis is limited by delays in reporting, consolidation and dissemination of data to relevant stakeholders. We fit and assessed a real-time predictive Google model for pertussis in California using weekly incidence data from 2009-2014. RESULTS AND DISCUSSION: The linear model was moderately accurate (r = 0.88). Our findings cautiously offer a complementary, real-time signal to enhance pertussis surveillance in California and help to further define the limitations and potential of Google-based epidemic prediction in the rapidly evolving field of digital disease detection. PMID- 26543675 TI - Conformations of a Long Polymer in a Melt of Shorter Chains: Generalizations of the Flory Theorem. AB - Large-scale simulations of the swelling of a long N-mer in a melt of chemically identical P-mers are used to investigate a discrepancy between theory and experiments. Classical theory predicts an increase of probe chain size R ~ P-0.18 with decreasing degree of polymerization P of melt chains in the range of 1 < P < N1/2. However, both experiment and simulation data are more consistent with an apparently slower swelling R ~ P-0.1 over a wider range of melt degrees of polymerization. This anomaly is explained by taking into account the recently discovered long-range bond correlations in polymer melts and corrections to excluded volume. We generalize the Flory theorem and demonstrate that it is in excellent agreement with experiments and simulations. PMID- 26543676 TI - The Role of Chemokines in Mesenchymal Stem Cell Homing to Wounds. AB - Significance: Mesenchymal stem cells (MSCs) are being administered to cutaneous wounds with the goal of accelerating wound closure and promoting regeneration instead of scar formation. An ongoing challenge for cell-based therapies is achieving effective and optimal targeted delivery and engraftment at the site of injury. Contributing to this challenge is our incomplete understanding of endogenous MSC homing to sites of injury. Recent Advances: Chemokines and their receptors are now recognized as important mediators of stem cell homing. To date, the most studied chemokine-chemokine receptor axis in MSC homing to wounds is CXCL12-CXCR4 but recent work suggests that CCL27-CCR10 and CCL21-CCR7 may also be involved. Critical Issues: Strategies to enhance chemokine-mediated MSC homing to wounds are using a variety of approaches to amplify the chemokine signal at the wound site and/or overexpress specific chemokine receptors on the surface of the MSC. Future Directions: Harnessing chemokine signaling may enhance the therapeutic effects of stem cell therapy by increasing the number of both exogenous and endogenous stem cells recruited to the site of injury. Alternatively, chemokine-based therapies directly targeting endogenous stem cells may circumvent the need for the time-consuming and costly isolation and expansion of autologous stem cells prior to therapeutic administration. PMID- 26543677 TI - Chemokine Regulation of Neutrophil Infiltration of Skin Wounds. AB - Significance: Efficient recruitment of neutrophils to an injured skin lesion is an important innate immune response for wound repair. Defects in neutrophil recruitment lead to impaired wound healing. Recent Advances: Chemokines and chemokine receptors are known to regulate neutrophil recruitment. Recent research advances reveal more mechanistic details about the regulation of chemokines and chemokine receptors on neutrophil egress from bone marrow, transmigration into the wound site, spatial navigation toward the necrotic skin tissue, and apoptosis induced clearance by efferocytosis. Critical Issues: Skin injury triggers local and systemic alterations in the expression of multiple chemotactic molecules and the magnitude of chemokine receptor-mediated signaling. The responses of a number of CXC and CX3C chemokines and their receptors closely associate with the temporal and spatial recruitment of neutrophils to wound sites during the inflammatory phase and promote the clearance of necrotic neutrophils during the transition into the proliferative phase. Functional aberrancy in these chemokines and chemokine receptor systems is recognized as one of the important mechanisms underlying the pathology of impaired wound healing. Future Directions: Future research should aim to investigate the therapeutic modulation of neutrophil activity through the targeting of specific chemokines or chemokine receptors in the early inflammatory phase to improve clinical management of wound healing. PMID- 26543678 TI - Chemokine Regulation of Angiogenesis During Wound Healing. AB - Significance: Angiogenesis plays a critical role in wound healing. A defect in the formation of a neovasculature induces ulcer formation. One of the challenges faced by the clinician when devising strategies to promote healing of chronic wounds is the initiation of angiogenesis and the formation of a stable vasculature to support tissue regeneration. Understanding the molecular factors regulating angiogenesis during wound healing will lead to better therapies for healing chronic wounds. Recent Advances: Classically, chronic wounds are treated with debridement to remove inhibitory molecules to reestablish angiogenesis and normal wound healing. The addition of platelet-derived growth factor (PDGF, becaplermin) has shown some promise as an adjunctive therapy, but better therapies are still needed. Current treatment strategies include investigating the outcome of augmenting cytokines locally to reduce the inflammatory response and promote angiogenesis. Critical Issues: The failure of wounds to form a new vasculature results in the inability of the wound to fully heal, and thus may develop into a chronic ulcer if left untreated. Inhibition of neovascularization commonly results from an overactive inflammatory response that includes an excessive chemokine response. Therefore, understanding how the chemokine response regulates neoangiogenesis will enhance our ability to develop new treatment strategies to improve neovascularization and wound healing. Future Directions: The ability to regulate the chemokine environment in chronic wounds may enhance the development of the neovasculature to reduce invasive treatments and enhance wound healing. Either inhibiting chemokines that promote a chronic inflammatory response or increasing the levels of proangiogenic chemokines may enhance angiogenesis in chronic wounds. PMID- 26543679 TI - Chemokines as Therapeutic Targets to Improve Healing Efficiency of Chronic Wounds. AB - Significance: Impaired wound healing leading to chronic wounds is an important clinical problem that needs immediate attention to develop new effective therapies. Members of the chemokine family seem to be attractive and amenable to stimulate the healing process in chronic wounds. Targeting specific chemokines and/or their receptors has the potential to modify chronic inflammation to acute inflammation, which will hasten the healing process. Recent Advances: Over the years, expression levels of various chemokines and their receptors have been identified as key players in the inflammatory phase of wound healing. In addition, they contribute to regulating other phases of wound healing making them key targets for novel therapies. Understanding the signaling pathways of these chemokines will provide valuable clues for modulating their function to enhance the wound healing process. Critical Issues: Inflammation, an important first stage process in wound healing, is dysregulated in chronic wounds; emerging studies show that chemokines play a crucial role in regulating inflammation. The knowledge gained so far is still limited in understanding the enormous complexity of the chemokine network during inflammation not just in chronic wounds but also in acute (normal) wounds. A much better understanding of the individual chemokines will pave the way for better targets and therapies to improve the healing efficiency of chronic wounds. Future Directions: Effective understanding of the interaction of chemokines and their receptors during chronic wound healing would facilitate the design of novel therapeutic drugs. Development of chemokine based drugs targeting specific inflammatory cells will be invaluable in the treatment of chronic wounds, in which inflammation plays a major role. PMID- 26543680 TI - Chemokine Involvement in Fetal and Adult Wound Healing. AB - Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing. Recent Advances: The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds. Critical Issues: Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways. Future Directions: Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets. PMID- 26543681 TI - The Role of Chemokines in Fibrotic Wound Healing. AB - Significance: Main dermal forms of fibroproliferative disorders are hypertrophic scars (HTS) and keloids. They often occur after cutaneous wound healing after skin injury, or keloids even form spontaneously in the absence of any known injury. HTS and keloids are different in clinical performance, morphology, and histology, but they all lead to physical and psychological problems for survivors. Recent Advances: Although the mechanism of wound healing at cellular and tissue levels has been well described, the molecular pathways involved in wound healing, especially fibrotic healing, is incompletely understood. Critical Issues: Abnormal scars not only lead to increased health-care costs but also cause significant psychological problems for survivors. A plethora of therapeutic strategies have been used to prevent or attenuate excessive scar formation; however, most therapeutic approaches remain clinically unsatisfactory. Future Directions: Effective care depends on an improved understanding of the mechanisms that cause abnormal scars in patients. A thorough understanding of the roles of chemokines in cutaneous wound healing and abnormal scar formation will help provide more effective preventive and therapeutic strategies for dermal fibrosis as well as for other proliferative disorders. PMID- 26543684 TI - Fabrication of nanoporous membranes for tuning microbial interactions and biochemical reactions. AB - New strategies for combining conventional photo- and soft-lithographic techniques with high-resolution patterning and etching strategies are needed in order to produce multiscale fluidic platforms that address the full range of functional scales seen in complex biological and chemical systems. The smallest resolution required for an application often dictates the fabrication method used. Micromachining and micropowder blasting yield higher throughput, but lack the resolution needed to fully address biological and chemical systems at the cellular and molecular scales. In contrast, techniques such as electron beam lithography or nanoimprinting allow nanoscale resolution, but are traditionally considered costly and slow. Other techniques such as photolithography or soft lithography have characteristics between these extremes. Combining these techniques to fabricate multiscale or hybrid fluidics allows fundamental biological and chemical questions to be answered. In this study, a combination of photolithography and electron beam lithography are used to produce two multiscale fluidic devices that incorporate porous membranes into complex fluidic networks in order to control the flow of energy, information, and materials in chemical form. In the first device, materials and energy were used to support chemical reactions. A nanoporous membrane fabricated with e-beam lithography separates two parallel, serpentine channels. Photolithography was used to pattern microfluidic channels around the membrane. The pores were written at 150 nm and reduced in size with silicon dioxide deposition from plasma enhanced chemical vapor deposition and atomic layer deposition. Using this method, the molecular weight cutoff of the membrane can be adapted to the system of interest. In the second approach, photolithography was used to fabricate 200 nm thin pores. The pores confined microbes and allowed energy replenishment from a media perfusion channel. The same device can be used for study of intercellular communication via the secretion and uptake of signal molecules. Pore size was tested with 750 nm fluorescent polystyrene beads and fluorescein dye. The 200 nm polydimethylsiloxane pores were shown to be robust enough to hold 750 nm beads while under pressure, but allow fluorescein to diffuse across the barrier. Further testing showed that extended culture of bacteria within the chambers was possible. These two examples show how lithographically defined porous membranes can be adapted to two unique situations and used to tune the flow of chemical energy, materials, and information within a microfluidic network. PMID- 26543683 TI - BMP-2 and BMP-2/7 Heterodimers Conjugated to a Fibrin/Hyaluronic Acid Hydrogel in a Large Animal Model of Mild Intervertebral Disc Degeneration. AB - Intervertebral disc (IVD) degeneration is etiologically associated with low back pain and is currently only treated in severe cases with spinal fusion. Regenerative medicine attempts to restore degenerated tissue by means of cells, hydrogels, and/or growth factors and can therefore be used to slow, halt, or reverse the degeneration of the IVD in a minimally invasive manner. Previously, the growth factors bone morphogenetic proteins 2 and 7 (BMP-2, -7) were shown to enhance disc regeneration, in vitro and in vivo. Since BMPs have only a short in vivo half-life, and to prevent heterotopic ossification, we evaluated the use of a slow release system for BMP-2 homodimers and BMP-2/7 heterodimers for IVD regeneration. BMP growth factors were conjugated to a fibrin/hyaluronic acid (FB/HA) hydrogel and intradiscally injected in a goat model of mild IVD degeneration to study safety and efficacy. Mild degeneration was induced in five lumbar discs of seven adult Dutch milk goats, by injections with the enzyme chondroitinase ABC. After 12 weeks, discs were treated with either FB/HA-hydrogel only or supplemented with 1 or 5 MUg/mL of BMP-2 or BMP-2/7. BMPs were linked to the FB/HA hydrogels using a transglutaminase moiety, to be released through an incorporated plasmin cleavage site. After another 12 weeks, goats were sacrificed and discs were assessed using radiography, MRI T2* mapping, and biochemical and histological analyses. All animals maintained weight throughout the study and no heterotopic bone formation or other adverse effects were noted during follow-up. Radiographs showed significant disc height loss upon induction of mild degeneration. MRI T2* mapping showed strong and significant correlations with biochemistry and histology as shown before. Surprisingly, no differences could be demonstrated in any parameter between intervention groups. To our knowledge, this is the first large animal study evaluating BMPs conjugated to an FB/HA-hydrogel for the treatment of mild IVD degeneration. The conjugated BMP-2 and BMP-2/7 appeared safe, but no disc regeneration was observed. Possible explanations include too low dosages, short follow-up time, and/or insufficient release of the conjugated BMPs. These aspects should be addressed in future studies. PMID- 26543685 TI - Evaluation of MR Spectroscopy and Diffusion-Weighted MRI in Postmenopausal Bone Strength. AB - AIM: To prospectively investigate the role of MR spectroscopy (MRS) and diffusion weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women. MATERIALS AND METHODS: Fifty postmenopausal women, who underwent dual-energy x-ray absorptiometry of the spine, were divided into three bone density groups (normal, osteopenia, and osteoporosis) based on T-score. Both MRS and DWI of the L3 vertebral body were performed to calculate the marrow fat content and apparent diffusion coefficient (ADC). The results were compared between three groups and correlated with BMD. RESULTS: Vertebral marrow fat content was significantly increased in the osteoporotic group when compared with that of the osteopenic group and the normal bone density group. ADC values in the osteoporotic, osteopenic, and normal bone density groups were 338, 408 and 464, respectively, with statistically significant differences (P < 0.001). A statistically significant positive correlation between T-scores and ADC existed (r=0.694, p value <0.001). The vertebral marrow fat content was negatively correlated to the bone density (r=-0.455, p< 0.001) and to marrow ADC (r= -0.302, p < 0.05). CONCLUSION: The postmenopausal women with osteoporosis exhibited a corresponding increase in vertebral marrow fat content as the bone density decreased. Marrow fat content and ADC were related to the bone density. MRS and DWI are helpful in evaluating the bone marrow changes in postmenopausal women. PMID- 26543686 TI - Inflammatory Myofibroblastic Tumor of the Left Sphenoid and Cavernous Sinus Successfully Treated with Partial Resection and High Dose Radiotherapy: Case Report and Review of the Literature. AB - Inflammatory myofibroblastic tumors, also known as plasma cell granulomas or inflammatory pseudotumors, are uncommon lesions that are known to arise in many areas of the body. They are uncommonly found in the skull base region where effective treatment can be difficult. Steroids and radiation therapy with gross total excision when possible remain the treatments of choice. However, the dosing of radiation remains controversial and many patients develop relapse despite medical management. We present the case of a patient who had an inflammatory myofibroblastic tumor of the sphenoid bone and cavernous sinus. He underwent partial surgical resection and transient steroid therapy. This was followed by high-dose fractionated radiotherapy. The patient demonstrated significant resolution in symptomatology and evidence of disease-free progression on repeat imaging. PMID- 26543682 TI - Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring. AB - Significance: Cutaneous scarring is an almost inevitable end point of adult human wound healing. It is associated with significant morbidity, both physical and psychological. Pathological scarring, including hypertrophic and keloid scars, can be particularly debilitating. Manipulation of the chemokine system may lead to effective therapies for problematic lesions. Recent Advances: Rapid advancement in the understanding of chemokines and their receptors has led to exciting developments in the world of therapeutics. Modulation of their function has led to clinically effective treatments for conditions as diverse as human immunodeficiency virus and inflammatory bowel disease. Potential methods of targeting chemokines include monoclonal antibodies, small-molecule antagonists, interference with glycosaminoglycan binding and the use of synthetic truncated chemokines. Early work has shown promising results on scar development and appearance when the chemokine system is manipulated. Critical Issues: Chemokines are implicated in all stages of wound healing leading to the development of a cutaneous scar. An understanding of entirely regenerative wound healing in the developing fetus and how the expression of chemokines and their receptors change during the transition to the adult phenotype is central to addressing pathological scarring in adults. Future Directions: As our understanding of chemokine/receptor interactions and scar formation evolves it has become apparent that effective therapies will need to mirror the complexities in these diverse biological processes. It is likely that sophisticated treatments that sequentially influence multiple ligand/receptor interactions throughout all stages of wound healing will be required to deliver viable treatment options. PMID- 26543687 TI - Relationship Between Regional Atherosclerosis and Adjacent Spinal Cord Histology. AB - INTRODUCTION: Scant data are available regarding ischemic insult to the spinal cord and the responsible blood supply. Therefore, we aimed to investigate a correlation between atherosclerosis of adjacent vessels and spinal cord ischemia. MATERIALS AND METHODS: In 20 unembalmed adult cadavers, samples of the vertebral arteries and aorta were removed and the degree of atherosclerosis with subsequent luminal occlusion was histologically analyzed. Next, adjacent segments of the spinal cord were harvested and submitted for immunohistological analysis of both neural and glial elements and blood supply. RESULTS: We identified proximal atherosclerosis in the majority of cadavers but with varying degrees of luminal occlusion. The greatest degree of luminal occlusion was found in the descending abdominal aorta. No specimen was found to have atherosclerosis of the anterior or posterior spinal or radicular arteries. No spinal cord histology showed signs of ischemia, even in specimens with a significant large parent vessel (vertebral artery and aorta) occlusion due to atherosclerosis. Neuropathology of these adjacent cord segments revealed no signs of ischemia or demyelination. CONCLUSIONS: Spinal cord ischemia is often misdiagnosed and can cause significant neurological compromise. However, based on our study, the degree of atherosclerosis of the adjacent parent vessel supply does not appear to be a predictor of neuronal and glial tissue damage of the adjacent spinal cord. PMID- 26543688 TI - Wait Times Experienced by Lung Cancer Patients in the BC Southern Interior to Obtain Oncologic Care: Exploration of the Intervals from First Abnormal Imaging to Oncologic Treatment. AB - BACKGROUND: Lung cancer is associated with rapid disease progression, which can significantly progress over a duration of four to eight weeks. This study examines the time interval lung cancer patients from the interior of British Columbia (BC) experience while undergoing diagnostic evaluation, biopsy, staging, and preparation for treatment. METHODS: A chart review of lung cancer patients (n=231) referred to the BC Cancer Agency Centre for the Southern Interior between January 1, 2010 and December 31, 2011 was performed. Time zero was defined as the date of the first abnormal chest imaging. Time intervals, expressed as median averages, to specialist consult, biopsy, oncologic referral, initial oncology consultation, and commencement of oncologic treatment were obtained. RESULTS: The median time interval from first abnormal chest imaging to a specialist consultation was 18 days (interquartile range, IQR, 7-36). An additional nine days elapsed prior to biopsy in the form of bronchoscopy, CT-guided biopsy, or sputum cytology (median; IQR, 3-21); if lobectomy was required, 18 days elapsed (median; IQR, 9-28). Eight days were required for pathologic diagnosis and subsequent referral to the cancer centre (median; IQR, 3-16.5). Once referral was received, 10 days elapsed prior to consultation with either a medical or radiation oncologist (median, IQR 5-18). Finally, eight days was required for initiation of radiation and/or chemotherapy (median; IQR, 1-15). The median wait time from detection of lung cancer on imaging to oncologic treatment in the form of radiation and/or chemotherapy was 65.5 days (IQR, 41.5-104.3). INTERPRETATION: Patients in the BC Southern Interior experience considerable delays in accessing lung cancer care. During this time, the disease has the potential to significantly progress and it is possible that a subset of patients may lose their opportunity for curative intent treatment. PMID- 26543689 TI - Simulation to Assist in the Selection Process of New Airway Equipment in a Children's Hospital. AB - INTRODUCTION: To provide an informed choice of equipment purchase, we sought to use simulation to allow medical providers an opportunity to evaluate two potential laryngoscopes. METHODS: The study followed a prospective, blinded comparison design. Participants were blinded to the laryngoscope brands by using alphabetic labels on the handles ("A" and "B"). Participants included a convenience sample of healthcare providers who perform intubation. Participants were allowed to perform intubation with the two laryngoscope brands on neonatal, child, and adolescent/adult airway simulators. After practicing with each of the two different laryngoscopes, participants completed an evaluation indicating their preference for one laryngoscope versus the other for each patient age group. RESULTS: Thirty-four healthcare providers participated in the study, including attendings, fellows, nurse practitioners, and transport team members from Neonatology, Pediatric Intensive Care, Anesthesiology, Emergency Medicine, Cardiac Intensive Care, and Otolaryngology. Participants overwhelmingly preferred brand 'A' (89%) over brand 'B' (11%). DISCUSSION: Providers overwhelmingly chose one laryngoscope over the other. Data from this evaluation were used to determine which of the two laryngoscope brands was purchased. Based on our experience, we feel other hospitals should consider the use of simulation to allow providers to examine, compare, and rate medical equipment prior to making purchasing decisions. PMID- 26543690 TI - Is There Any Role of Inhalational Corticosteroids in the Prophylaxis of Post Traumatic Fat Embolism Syndrome? AB - Fat embolism syndrome (FES) is primarily a lung parenchymal disorder resulting from interstitial and alveolar inflammation triggered by the lipid metabolites in blood circulation. The 'low-dose' corticosteroid is supposed to have a prophylactic effect on the incidence of the FES and arterial hypoxemia by reducing this inflammatory response. It is expected that inhaled corticosteroids (ciclesonide aerosol) may prevent the development of hypoxemia or fat embolism syndrome in high-risk patients by reducing this inflammatory response. Metered dose inhaler (MDI) steroid preparations can reach the lung parenchyma with minimal systemic effect. Sixty cases of polytrauma patients presenting within eight hours of injury were randomly allocated into one of the two groups. In Group 1 (n1=30) ciclesonide, 640 mcg, was given with a metered dose inhaler and repeated once again after 24 hours, whereas Group 2 (n2=30) was taken as control and observed for 72 hours for any episode of hypoxia. The outcome was assessed using Schonfeld's criteria for the eventual outcome of subclinical or clinical FES. Out of 30 patients in each group, six patients developed subclinical FES, whereas three from ciclesonide prophylaxis group and eight from controls developed clinical FES. There is no statistical significance found between the eventual outcomes of subclinical or clinical FES between the ciclesonide prophylaxis and control group. Although there was a trend seen in the possible preventive efficacy of inhalational steroid in the present study, it did not reach the statistically significant level. The prophylactic role of inhalational steroid in post-traumatic subclinical and clinical FES is statistically insignificant in the present study. PMID- 26543691 TI - Attitude of Basic Science Medical Students Toward Interprofessional Collaboration. AB - PURPOSE: Interprofessional collaboration (IPC) and interprofessional education (IPE) are increasingly emphasized in the education of health professions. Xavier University School of Medicine, a Caribbean medical school admits students from the United States, Canada, and other countries to the undergraduate medical course. The present study was carried out to obtain information about the attitude toward IPC among basic science medical students and note differences, if any, among different subgroups. METHODS: The study was conducted among first to fifth semester students during July 2015 using the previously validated Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC). Gender, age, semester, and nationality were noted. Participants' agreement with a set of 20 statements was studied. Mean total scores, working relationship, and accountability scores were calculated and compared among different subgroups of respondents (p<0.05). RESULTS: Sixty-seven of the 71 students (94.4%) participated. Cronbach's alpha value of the questionnaire was 0.827, indicating good internal consistency. The mean total score was 104.48 (maximum score 140) while the working relationship and accountability scores were 63.51 (maximum score 84) and 40.97 (maximum score 56), respectively. Total scores were significantly higher among third-semester students and students of Canadian nationality. Working relationship and accountability scores were higher among first and third-semester students. CONCLUSION: The total working relationship and accountability scores were lower compared to those obtained in a previous study. Opportunities for IPE and IPC during the basic science years should be strengthened. Longitudinal studies in the institution may be helpful. Similar studies in other Caribbean medical schools are required. PMID- 26543692 TI - Spontaneous Thrombosis and Subsequent Recanalization of a Developmental Venous Anomaly. AB - Developmental venous anomalies (DVA) are among the most common congenital malformations of the cerebral angioarchitecture. Spontaneous thrombosis of this entity is rare, and our review of the literature found only 31 reported cases of symptomatic spontaneous thrombosis of developmental venous anomalies. Here, we report a unique case describing the spontaneous thrombosis of a DVA leading to venous infarction and subsequent recanalization. The patient was a previously healthy 21-year-old male who presented with an acute onset of partial seizures. Following negative hypercoagulability studies and along with CT (computed tomography) and MR (magnetic resonance) imaging, the patient was treated with anticoagulant therapy and demonstrated complete functional recovery. Knowledge from our literature review of similar cases combined with the experience gained from this patient's treatment leads us to suggest that spontaneous DVA thrombosis and venous infarction generally has a good outcome despite initially devastating neurologic deficits. Additionally, the rarity of spontaneous DVA thromboses lends itself to the need to identify possible predisposing risk factors, chief amongst these being hypercoagulopathies. PMID- 26543693 TI - Cognitive Impairment After Stroke. AB - BACKGROUND: Vascular dementia is extremely common and contributes to stroke associated morbidity and mortality. The study of vascular dementia may help to plan preventive interventions. AIMS: To study the frequency of cognitive impairment after stroke in a series of consecutive patients with acute stroke, along with factors which influence it. METHODS: Fifty adults with acute infarct or hemorrhage (as seen on computed tomography of the brain) were included in the study. The National Institute of Health Stroke Scale (NIHSS) and Barthel's Index scores were done. Cognitive testing was done by PGI Battery of Brain Dysfunction (PGI-BBD) and Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (SIQCODE). Statistical analysis was by Student's t-test, Chi-square test, Fisher's exact test, and Mann-Whitney U test. RESULTS: Mean age of patients was 61.82 years; males and ischemic strokes predominated. Dementia was seen in 30%, cognitive impairment no dementia (CIND) in 42%, and normal cognition in 28% patients. Factors associated with vascular cognitive impairment included old age, male sex, low education, hemorrhages, recurrent or severe stroke, silent infarcts, severe cortical atrophy, and left hemispheric or subcortical involvement. CONCLUSIONS: Up to 72% of patients have some form of cognitive impairment after a stroke. Secondary stroke prevention could reduce the incidence of vascular dementia. PMID- 26543694 TI - Transvaginal Mini-Laparoscopic Splenectomy. AB - We aimed to perform a more and more minimal invasive splenectomy by only through two 5 mm umbilical trocars and one vaginal trocar. A 43-year-old female (BMI 31 kg/m(2), ASA II) with immune thrombocytopenic purpura was planned for splenectomy. She had a history of a previous cesarean section for three times. Two 5 mm trocars were inserted separately through the umbilicus. We did not use any single port device or similar modifications. A 15 mm trocar was inserted through the posterior fornix of the vagina under umbilical laparoscopic vision. The 5 mm umbilical ports were used for camera and retraction of the spleen. The transvaginal port was used for dissection and division of the spleen by a 10-mm LigaSure Atlas vessel sealing system. No clips or staples were used. As the spleen became completely free in the abdomen, it was removed through the vagina in a bag without fragmentation. The operating time was 200 minutes and the blood loss was minimal (< 20 ml). No drain or abdominal fascia suturing was used but closing the posterior fornix of the vagina. Her postoperative course was uneventful and she was discharged on day two without complication. She did not require any analgesics postoperatively. Platelet values increased to 408.000 mm(3) in the follow-up. To the best of our knowledge, this report described the most minimal invasive splenectomy even. Additionally, it provided an unfragmented spleen extraction. The transvaginal approach seems to be a feasible way to perform natural orifice splenectomy. PMID- 26543695 TI - Association of Ego Defense Mechanisms with Academic Performance, Anxiety and Depression in Medical Students: A Mixed Methods Study. AB - BACKGROUND: Ego defense mechanisms are unconscious psychological processes that help an individual to prevent anxiety when exposed to a stressful situation. These mechanisms are important in psychiatric practice to assess an individual's personality dynamics, psychopathologies, and modes of coping with stressful situations, and hence, to design appropriate individualized treatment. Our study delineates the relationship of ego defense mechanisms with anxiety, depression, and academic performance of Pakistani medical students. METHODS: This cross sectional study was done at CMH Lahore Medical College and Fatima Memorial Hospital Medical and Dental College, both in Lahore, Pakistan, from December 1, 2014 to January 15, 2015. Convenience sampling was used and only students who agreed to take part in this study were included. The questionnaire consisted of three sections: 1) Demographics, documenting demographic data and academic scores on participants' most recent exams; 2) Hospital Anxiety and Depression Scale (HADS); and 3) Defense Style Questionnaire-40 (DSQ-40). The data were analyzed with SPSS v. 20. Mean scores and frequencies were calculated for demographic variables and ego defense mechanisms. Bivariate correlations, one-way ANOVA, and multiple linear regression were used to identify associations between academic scores, demographics, ego defense mechanisms, anxiety, and depression. RESULTS: A total of 409 medical students participated, of whom 286 (70%) were females and 123 (30%) were males. Mean percentage score on the most recent exams was 75.6% in medical students. Bivariate correlation revealed a direct association between mature and neurotic ego defense mechanisms and academic performance, and an indirect association between immature mechanisms and academic performance. One way ANOVA showed that moderate levels of anxiety (P < .05) and low levels of depression (P < .05) were associated with higher academic performance. CONCLUSION: There was a significant association between academic performance and ego defense mechanisms, anxiety, and depression levels in our sample of Pakistani medical students. PMID- 26543696 TI - Comparison of SpO2 values from different fingers of the hands. AB - Pulse oximetry is a frequently used tool in anesthesia practice. Gives valuable information about arterial oxygen content, tissue perfusion and heart beat rate. In this study we aimed to provide the comparison of peripheral capillary hemoglobin oxygen saturation (SpO2) values among every finger of the two hands. Thirty-seven healthy volunteers from operative room stuffs between the ages of 18 30 years were enrolled in the study. They were monitored after 5 min of rest. After their non invasive blood pressure, heart rate, fasting time and body temperature were measured, SpO2 values were obtained from every finger and each of two hands fingers with the same pulse oximetry. All the SpO2 values were obtained after at least 1 min of measurement period. A total of 370 SpO2 measurements from 37 volunteers were obtained. The highest average SpO2 value was measured from right middle finger (98.2 % +/- 1.2) and it was statistically significant when compared with right little finger and left middle finger. The second highest average SpO2 value was measured from right thumb and it was statistically significant only when compared with left middle finger (the finger with the lowest average SpO2 value) (p < 0.05). SpO2 measurement from the fingers of the both hands with the pulse oximetry, the right middle finger and right thumb have statistically significant higher value when compared with left middle finger in right-hand dominant volunteers. We assume that right middle finger and right thumb have the most accurate value that reflects the arterial oxygen saturation. PMID- 26543697 TI - Seasonal population density and winter survival strategies of endangered Kashmir gray langur (Semnopithecus ajax) in Dachigam National Park, Kashmir, India. AB - The population density of Kashmir gray langurs (Semnopithecus ajax) was studied in Dachigam National Park (DNP), Kashmir using distance sampling method. A total of 13 transects (1.5-2.5 km in length) were surveyed in the intensive study area (~90 km(2)) yielding 170 encounters in different seasons of the study period (2011-2013). Some aspects of behavior and feeding were also studied during the winter months (Dec-Feb) of 2012 and 2013 inside DNP. We used instantaneous scan sampling to collect behavioral data determining the time budget and diet of langurs in winter conditions. Results suggested that the density of Kashmir gray langurs varied marginally across seasons, with the highest density recorded during winter and lowest during summer season. Langurs spent most of their time in carrying out various social activities (34.32 %) and least in resting (18.41 %). Langurs fed upon 13 plant species (belonging to 12 families) and consumed a substantial proportion of bark (37.4 %) in their diet. We conclude that langur density is low in DNP as compared to other plain areas of the Indian subcontinent and langurs in DNP have balanced their time budget and diet so as to increase their chances of survival in the unfavorably cold and food scarce winter conditions. PMID- 26543698 TI - Malaysian and Singaporean students' affective characteristics and mathematics performance: evidence from PISA 2012. AB - This paper attempts to identify the extent to which the affective characteristics of Malaysian and Singaporean students' attainment compared to the OECD average in Programme for International Student Assessment (PISA) 2012, and examine the influence of students' affective characteristics, gender, and their socioeconomic status on mathematics performance at both student and school levels. Sample consisted of 5197 and 5546 15-year-old Malaysian and Singaporean students. Data were analysed using hierarchical linear modelling approach with HLM 7.0 software. Results showed that the Index of economic, social, and cultural status (ESCS), mathematics self-efficacy, and mathematics anxiety have significant effects on mathematics performance in Malaysia and Singapore at the student level. Proportion of boys at the school level has no significant effects on mathematics performance for both Malaysian and Singaporean students. ESCS mean at the school level has positive and significant effects on mathematics performance in Malaysia, but not in Singapore. Limitations, implications, and future studies were discussed. PMID- 26543699 TI - Photoelectrochemical properties of mesoporous NiO x deposited on technical FTO via nanopowder sintering in conventional and plasma atmospheres. AB - Nanoporous nickel oxide (NiO x ) has been deposited with two different procedures of sintering (CS and RDS). Both samples display solid state oxidation at about 3.1 V vs Li+/Li. Upon sensitization of CS/RDS NiO x with erythrosine b (ERY), nickel oxide oxidation occurs at the same potential. Impedance spectroscopy revealed a higher charge transfer resistance for ERY-sensitized RDS NiO x with respect to sensitized CS NiO x . This was due to the chemisorption of a larger amount of ERY on RDS with respect to CS NiO x . Upon illumination the photoinduced charge transfer between ERY layer and NiO x could be observed only with oxidized CS. Photoelectrochemical effects of sensitized RDS NiO x were evidenced upon oxide reduction. With the addition of iodine RDS NiOx electrodes could give the reduction iodine -> iodide in addition to the reduction of RDS NiO x . p-type dye sensitized solar cells were assembled with RDS NiO x photocathodes sensitized either by ERY or Fast Green. Resulting overall efficiencies ranged between 0.02 and 0.04 % upon irradiation with solar spectrum simulator (I in: 0.1 W cm(-2)). PMID- 26543700 TI - Idiopathic fourth ventricle outlet obstruction successfully treated by endoscopic third ventriculostomy: a case report. AB - INTRODUCTION: Fourth ventricle outlet obstruction (FVOO) is a rare cause of obstructive hydrocephalus. We describe a case of idiopathic FVOO that was successfully treated with endoscopic third ventriculostomy (ETV). CASE REPORT: A 3-year old boy without any remarkable medical history presented with a headache and vomiting. Computed tomography (CT) images, which had incidentally been taken 2 years previously due to a minor head injury, showed no abnormality. Magnetic resonance imaging on admission showed tetra-ventricular hydrocephalus associated with the dilatation of the fourth ventricle outlets, without any obstructive lesions. However, CT ventriculography, involving contrast medium injection through a ventricular catheter, suggested mechanical obstruction of the cerebrospinal fluid (CSF) at the fourth ventricle outlets. Thus, the patient was diagnosed with FVOO and ETV was performed; the hydrocephalus was subsequently resolved. Although hydrocephalus recurred 1 year postoperatively, re-ETV for the highly stenosed fenestration successfully resolved this condition. CONCLUSIONS: ETV should be considered for FVOO treatment, particularly in idiopathic cases without CSF malabsorption. PMID- 26543701 TI - Genetic polymorphism study at 15 autosomal locus in central Indian population. AB - The analysis of 15 autosomal STR locus (TH01, D3S1358, vWA, D21S11, TPOX, D7S820, D19S433, D5S818, D2S1338, D16S539, CSF1PO, D13S317, FGA, D18S51, D8S1179) was done in 582 healthy unrelated individuals (Male-366, Female-216) originating from the various geographical regions of Madhya Pradesh, India. All locus fall under Hardy-Weinberg equilibrium except TPOX. These STR loci were highly informative and discriminating with combined power of discrimination (CPD) >0.99999. Locus wise allele frequencies of the studied population were compared with the other published populations. Also the Clustering pattern and genetic distance of studied populations is compared and presented with various populations. The studied population showed the genetic proximity with geographically close populations of India and significant genetic variation with distant populations which is also evident by clustering pattern of the NJ tree and the PCA plot. PMID- 26543702 TI - Antibacterial activities of Fagara macrophylla, Canarium schweinfurthii, Myrianthus arboreus, Dischistocalyx grandifolius and Tragia benthamii against multi-drug resistant Gram-negative bacteria. AB - Bacterial infections caused by multidrug resistant phenotypes constitute a worldwide health concern. The present study was designed to evaluate the in vitro antibacterial activities of the methanol extracts of five medicinal plants: Fagara macrophylla, Canarium schweinfurthii, Myrianthus arboreus, Dischistocalyx grandifolius and Tragia benthamii against a panel of 28 multidrug resistant Gram negative bacterial strains. The liquid broth microdilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts. The best activity was recorded with Canarium schweinfurthii bark extract, MIC values ranging from 32 to 1024 ug/mL being recorded against 85.7 % tested bacteria. Broad spectra of antibacterial activities were also obtained with both bark and leaf extracts from Myrianthus arboreus (78.6 %) as well as the bark extract from Fagara macrophylla (75.0 %). The lowest MIC value of 32 ug/mL was obtained with Canarium schweinfurthii bark extract against Klebsiella pneumoniae KP63 strain. The results of this work provide baseline information for the use of the studied plants, and mostly Fagara macrophylla, Canarium schweinfurthii and Myrianthus arboreus in the treatment of bacterial infections including multidrug resistant phenotypes. PMID- 26543703 TI - Evaluation of non-genetic factors affecting calf growth, reproductive performance and milk yield of traditionally managed Sheko cattle in southwest Ethiopia. AB - The study was conducted to estimate calf growth, reproductive performance and milk yield of Ethiopia Sheko cattle and to assess non-genetic factors affecting their performance in their home tract as a step towards designing sustainable cattle conservation and improvement strategy. All the growth traits considered in the study were significantly affected by all non-genetic factors considered except for the fixed effects of Agro ecological zones (AEZs) and season of birth which were not significant for post weaning daily gain. Calving interval (CI) and days open (DO) were significantly influenced by AEZs, season and dam parity. Cows that calved in lowland had shorter CI and DO than cows which calved in midland. Cows that calved in short rainy season had Short CI and DO than those calved during dry season or long rainy season. Cows which calved for the first time had the longest CI and DO from the other parities whereas cows on their fifth parity had the shortest CI and DO. AEZ significantly affected lactation milk yield (LMY) and lactation length (LL), but not significant on daily milk yield (DMY) and 305 days yield (305DY). Season was significant on all milk traits considered except DMY. Parity effect was significant on LMY and 305DY, whereas DMY and LL were not affected. The non-genetic factors had significant effects for all of the reproductive; and many of the growth and milk performance traits considered and hence will need to be considered in cattle breed improvement program. PMID- 26543704 TI - Cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells. AB - The supraneural body was identified in the adult lamprey, and its secretions induced the death of a variety of tumor cells but had no effect on normal cells. The cell secretions from different lamprey tissues were separated, and these secretions killed human tumor cells to varying degrees. The cell secretions induced remarkable cell morphological alterations such as cell blebbing, and the plasma membrane was destroyed by the secretions. In addition, the secretions induced morphological alterations of the mitochondria, cytoskeletal structure, and endoplasmic reticulum, eventually leading to cell death. These observations suggest the presence of a novel protein in the lamprey and the possibility of new applications for the protein in the medical field. PMID- 26543705 TI - Safety and effectiveness of minimally invasive sacroiliac joint fusion in women with persistent post-partum posterior pelvic girdle pain: 12-month outcomes from a prospective, multi-center trial. AB - Postpartum posterior pelvic girdle pain (PPGP) affects nearly 20 % of women who experience back pain in the peripartum period. The sacroiliac joint is a source of this pain in 75 % of women with persistent PPGP. A subset of women will fail to obtain acceptable pain relief from the current array of non-surgical treatment options. The purpose of this study is to assess the safety and effectiveness of minimally invasive sacroiliac (SI) joint fusion in women with chronic SI joint dysfunction whose pain began in the peri-partum period whose symptoms were recalcitrant to non-surgical management. A sub-group analysis of subjects with sacroiliac joint disruption and/or degenerative sacroiliitis enrolled in a prospective, multi-center trial of SI joint fusion was performed. Subjects with PPGP were identified and compared with women without PPGP and with men. Of 172 enrolled subjects, 52 were male, 100 were females without PPGP and 20 females had PPGP. PPGP subjects were significantly younger (43.3 years, vs. 52.8 for females without PPGP and 50.5 for men, p = 0.002). There were no differences in any other demographic or baseline clinical measure. Women with PPGP experienced a significant improvement in pain (-51 mm on VAS), function (-20.6 pts on ODI) and quality of life (SF-36 PCS +10.4, MCS +7.2, EQ-5D +0.31) at 12 months after surgery. These improvements were characteristic of the overall study results; no difference was detected between sub-groups. The sacroiliac joint can be a source of pain in women with persistent PPGP and should be investigated as a pain generator. In this study, women with carefully diagnosed chronic SI joint pain from PPGP recalcitrant to conservative therapies experienced clinically beneficially improvements in pain, disability and quality of life after minimally invasive SI joint fusion using a series of triangular porous plasma spray coated implants. PMID- 26543706 TI - Discovery of novel 1,2,3-triazole derivatives as anticancer agents using QSAR and in silico structural modification. AB - Considerable attention has been given on the search for novel anticancer drugs with respect to the disease sequelae on human health and well-being. Triazole is considered to be an attractive scaffold possessing diverse biological activities. Structural modification on the privileged structures is noted as an effective strategy towards successful design and development of novel drugs. The quantitative structure-activity relationships (QSAR) is well-known as a powerful computational tool to facilitate the discovery of potential compounds. In this study, a series of thirty-two 1,2,3-triazole derivatives (1-32) together with their experimentally measured cytotoxic activities against four cancer cell lines i.e., HuCCA-1, HepG2, A549 and MOLT-3 were used for QSAR analysis. Four QSAR models were successfully constructed with acceptable predictive performance affording R CV ranging from 0.5958 to 0.8957 and RMSECV ranging from 0.2070 to 0.4526. An additional set of 64 structurally modified triazole compounds (1A-1R, 2A-2R, 7A-7R and 8A-8R) were constructed in silico and their predicted cytotoxic activities were obtained using the constructed QSAR models. The study suggested crucial moieties and certain properties essential for potent anticancer activity and highlighted a series of promising compounds (21, 28, 32, 1P, 8G, 8N and 8Q) for further development as novel triazole-based anticancer agents. PMID- 26543707 TI - Leg ulcer in a patient with Rothmund-Thomson syndrome. AB - BACKGROUND: Rothmund-Thomson syndrome is a rare genetic condition exhibiting some dermatological, craniofacial, ophthalmological, and central nervous system abnormalities. CASE DESCRIPTION: A 51-year-old male patient, diagnosed with Rothmund-Thomson syndrome, attended to our outpatient clinic with complaint of unhealing wound in lower part of his left leg. Over this period, he had received various local therapies such as creams, wound dressings and hyperbaric oxygen therapy but no progress could be achieved. The wound gradually enlarged. Negative pressure wound therapy was applied at -125 mmHg for 20 days. Wound was finally covered with split-thickness skin graft. DISCUSSION AND EVALUATION: There is only one case of Rothmund-Thomson syndrome with leg ulcer reported in the literature. However, complete closure has not been achieved with non-surgical therapies in this case. Therefore we performed negative pressure wound therapy followed by skin grafting. CONCLUSIONS: It is useful to treat therapy resistant wounds in Rothmund-Thomson syndrome by negative pressure, which can preserve residual vital tissue, and help clear away necrotizing tissue effectively and close the wound promptly. PMID- 26543708 TI - Long-term outcomes of colectomy surgery among patients with ulcerative colitis. AB - The objective of this study was to evaluate long-term health-related quality of life outcomes among patients who had a colectomy within the previous 10 years. A cross-sectional survey was administered to consecutive patients >=18 years of age with ulcerative colitis who had a colectomy within the last 10 years from centers in Canada, Australia, and the United Kingdom. Data were extracted from medical chart reviews to confirm selected self-reported patient characteristics. Of 351 survey respondents, 49 % were male and the median age was 40 years (interquartile range 30-52). Respondents were diagnosed with UC a median of 9.2 (5.7-15.1) years prior to the survey and first surgery occurred a median of 3.7 (2.1-5.8) years ago. Although most respondents (84 %) reported improved quality of life compared to the status before surgery, 81 % experienced problems in at least one of the following areas: depression, work productivity, restrictions in diet, body image, and sexual function. According to HADS scores, 30 and 17 % of survey respondents experienced anxiety and depression, respectively. Among moderate to severe UC patients pre-colectomy, 27 % of men and 28 % of women reported that their sexual life was worse now than before surgery. The mean EQ-5D utility index score overall was 0.79 (95 % confidence interval 0.77-0.81). Quality of life after colectomy for UC is generally good, but there are persistent quality of life issues that impact multiple domains, including psychological and sexual functioning. PMID- 26543709 TI - Formulation of a generalised switching CFAR with application to X-band maritime surveillance radar. AB - A generalisation of a switching based detector is examined, allowing the construction of such detectors for target detection in any clutter model of interest. Such detectors are important in radar signal processing because they are robust solutions to the management of interference. Although formulated in general terms, the theory is applied to the design of a switching constant false alarm rate detector for X-band maritime surveillance radar. It is shown that such a detector manages the problem of interference better than standard detection processes. PMID- 26543711 TI - A first digit theorem for powerful integer powers. AB - For any fixed power exponent, it is shown that the first digits of powerful integer powers follow a generalized Benford law (GBL) with size-dependent exponent that converges asymptotically to a GBL with the inverse double power exponent. In particular, asymptotically as the power goes to infinity these sequences obey Benford's law. Moreover, the existence of a one-parametric size dependent exponent function that converges to these GBL's is established, and an optimal value that minimizes its deviation to two minimum estimators of the size dependent exponent is determined. The latter is undertaken over the finite range of powerful integer powers less than [Formula: see text], where [Formula: see text] is a fixed power exponent. PMID- 26543712 TI - Correlation of the clinical parameters with sonographic findings of hemorrhagic cystitis in pediatric hematooncology patients. AB - To find a relationship between clinical and sonographic appearance of hemorrhagic cystitis (HC) in pediatric hematooncology patients. Clinical and sonographic findings of 31 children (M:F = 18:13; mean age, 12.7 years) with HC in pediatric hematooncology patients were reviewed. For each patient, the onset of HC after transplantation, use of bladder-toxic agent, presence of BK viruria, and duration of disease were reviewed. Sonographic findings including bladder wall thickness (BWT), the type of bladder wall thickening (nodular vs. diffuse), occurrence of hydronephrosis or pyelonephritis were reviewed. We analyzed sonographic appearance and clinical manifestations of HC. HC occurred within 4 months after HSCT/BMT. 27 patients (87.0 %) were positive for BK viruria and 24 patients (77.4 %) took bladder-toxic agents. On sonography, nodular type bladder wall thickening was more frequent (54.8 %), and BWT was thicker in this group (p = 0.003). There was a positive correlation between the BWT on initial sonography and duration of cystitis (r (2) = 0.340). Hydronephrosis developed in 25.8 % of patients with HC, and as HC persisted longer, hydronephrosis occurred more (p = 0.004). In patients with HC after HSCT/BMT, the BWT on initial sonography correlates well with the duration of cystitis. And, longer time of HC develops the risk of hydronephrosis. PMID- 26543710 TI - Non-O1, non-O139 Vibrio cholerae bacteraemia: case report and literature review. AB - Non-O1, non-O139 Vibrio cholerae (NOVC) are increasingly frequently observed ubiquitous microorganisms occasionally responsible for intestinal and extra intestinal infections. Most cases involve self-limiting gastroenteritis or ear and wound infections in immunocompetent patients. Bacteraemia, which have been described in patients with predisposing factors, are rare and poorly known, both on the clinical and therapeutic aspects. We describe a case of NOVC bacteraemia and a systematic literature review in PubMed conducted up to November 2014 using a combination of the following search terms: "Vibrio cholerae non-O1" and "bacter(a)emia". The case was a 70 year-old healthy male subject returning from Senegal and suffering from NOVC bacteraemia associated with liver abscesses. Disease evolution was favourable after 2 months' therapy (ceftriaxone then ciprofloxacin). Three hundred and fifty cases of NOVC bacteraemia have been identified in the literature. The majority of patients were male (77 %), with a median age of 56 years and presenting with predisposing conditions (96 %), such as cirrhosis (55 %) or malignant disease (20 %). Diarrhoea was inconstant (42 %). Mortality was 33 %. The source of infection, identified in only 25 % of cases, was seafood consumption (54 %) or contaminated water (30 %). Practitioners should be aware of these infections, in order to warn patients with predisposing conditions, on the risk of ingesting raw or undercooked seafood or bathing in potentially infected waters. PMID- 26543713 TI - Whole body vibration therapy: a novel potential treatment for type 2 diabetes mellitus. AB - There is a worsening epidemic of obesity and diabetes in the world. Life style interventions including dietary changes and increase in exercise can improve glucose metabolism and health in general. However, standard exercise programs are strenuous, time-consuming, and thus have low long-term compliance issues. We tested the feasibility of using high frequency, low amplitude whole body vibration (WBV) therapy to improve glucose metabolism in young type 2 diabetic (T2DM) mice. We also aimed to investigate the postulated anti-inflammatory and cytoprotective properties of WBV. Male db/db and db/m mice were exposed to high frequency, low-amplitude WBV. Outcome parameters comprised of body weight, hemoglobin A1c (HbA1c) level, as well as interleukin (IL)-17 (a marker of helper T cells), forkhead box P3 (Foxp3; a marker of regulatory T cells), and gammaH2AX (an index of DNA injury) expression. Furthermore, a 24 h metabolic cage study was carried out immediately after the WBV protocol and fluid intake, urine excretion and urine osmolality were determined. WBV did not affect body weight but improved HbA1c levels in db/db mice. Vibrated db/db mice demonstrated less fluid intake and urine excretion but better urinary concentrating ability than their non vibrated controls. Pro-inflammatory changes were significantly reduced, as indicated by reduced IL-17 but increased Foxp3 expression. WBV reduced gammaH2AX in db/db mice suggestive of cytoprotective effect. However, WBV was largely without significant effects on assessed parameters in db/m mice. Collectively, our findings suggest that daily, short duration WBV may improve glycemic control, polydipsia, polyuria, and urine osmolality in T2DM in association with reduced inflammation. Thus, WBV may be a viable adjunctive treatment strategy in T2DM. PMID- 26543714 TI - Correlation between patients' anatomical characteristics and interfractional internal prostate motion during intensity modulated radiation therapy for prostate cancer. AB - Intensity modulated radiation therapy (IMRT) is one of a standard treatment for localized prostate cancer. Although lower complication is expected for smaller target margin, determination of optimal margin is important. For bony-structure based registration, internal prostate motion is the main factor determining the margin from clinical target volume to planning target volume. The purpose of this study was to measure interfractional internal motion of the prostate and to identity the factors which enlarge or reduce the margin, with special focus on patients' anatomical characteristics. The 586 image sets of 16 patients acquired with megavoltage cone beam computed tomography were analyzed. For each patient, prostate shift in three directions was recorded for each fraction to calculate the required margin. Correlations between these values and patients' anatomical characteristics were evaluated. The posteriorly required margin correlated positively with rectal volume and rectal mean area (p = 0.015 and p = 0.008), while random error in lateral, craniocaudal and anteroposterior direction correlated negatively (p = 0.014, 0.04 and 0.0026, respectively) with body mass index (BMI). In addition to the previously identified factor of distended rectum, BMI was newly identified as another significant factor influencing interfractional internal prostate motion. PMID- 26543715 TI - The growth rate of "clinically significant" renal cancer. AB - Surveillance studies of enhancing renal masses report on a mean tumor growth rate of about 0.3 cm/year. In most of these studies however, only small tumors in elderly patients were followed. In the current report, we attempt to evaluate the growth rate of "clinically significant" renal carcinomas defined as tumors that were treated immediately upon diagnosis. 46 patients (mean age 64 years SD 11 years) were treated for renal carcinoma. All had a cross-sectional imaging studies performed 6-60 months prior to diagnosis of kidney cancer demonstrating no tumor. Tumor growth rate was calculated by dividing tumor's largest diameter by the time interval between the normal kidney imaging and diagnosis of renal cancer. Mean tumor diameter was 4.5 cm (SD 2.4 cm). Mean time period from the normal imaging to diagnosis of renal cancer was 33.6 months (SD 18 months). According to the proposed model, the average growth rate of "clinically significant" renal carcinomas was 2.13 cm/year (SD 1.45, range 0.2-6.5 cm/year). Tumor growth rate correlated inversely with patient's age (p = 0.007). Patient gender or Fuhrman's grade did not correlate however. The growth rate of "clinically significant" renal cancer appears to be higher than the rate reported in surveillance trials. Renal tumors tend to grow faster in young patients. As such, variable growth rate should be taken into account when considering active surveillance in young patients and when designing trials for evaluation of anti cancer agents. PMID- 26543716 TI - Spark plasma sintering of alumina nanopowders produced by electrical explosion of wires. AB - Alumina nanopowders produced by electrical explosion of wires were sintered using the spark plasma sintering technique. The results of XRD analysis show that the main phase in the compacted nanopowders is alpha-Al2O3. According to the SEM observations, the sintered alumina nanopowder consists of micron-sized faceted grains and nano-sized necked grains. The increase in sintering temperature resulted in a higher density of the sintered powders: from 78.44 to 98.21 % of theoretical density. PMID- 26543717 TI - Psychrophilic pseudomonas in antarctic freshwater lake at stornes peninsula, larsemann hills over east Antarctica. AB - The Larsemann Hills is an ice-free area of approximately 50 km(2), located halfway between the Vestfold Hills and the Amery Ice Shelf on the south-eastern coast of Prydz Bay, Princess Elizabeth Land, East Antarctica (69o30'S, 76o19'58"E). The ice-free area consists of two major peninsulas (Stornes and Broknes), four minor peninsulas, and approximately 130 islands. The Larsemann Hills area contains more than 150 lakes at different Islands and Peninsulas. Nine lake water samples were collected in a gamma sterilized bottles and were kept in an ice pack to prevent any changes in the microbial flora of the samples during the transportation. The water samples were transported to the lab in vertical position maintaining the temperature 1-4 degrees C with ice pack enveloped conditions. Samples were studied for Psychrophilic bacterial count, Pseudomonas spp., Staphylococcus aureus, Salmonella and Total MPN Coliform per 100 ml. Psychrophillic counts were found in the range of 12 cfu to 1.6 * 10(2) cfu in all the samples. MPN Coliform per 100 ml was found to be absent in all the samples. No growth and characteristics colonies observed when tested for Salmonella and S.aureus. Pseudomonas sp. was found in ST-2 lake water sample as characteristics colonies (Optimum Growth) were observed on selective media at 22 and 25 degrees C. Further several biochemical tests were also performed to confirm the presence of this Potential Psychrophilic Pseudomonas sp. for its further application in Science and Technology. PMID- 26543718 TI - Accurate mobile malware detection and classification in the cloud. AB - As the dominator of the Smartphone operating system market, consequently android has attracted the attention of s malware authors and researcher alike. The number of types of android malware is increasing rapidly regardless of the considerable number of proposed malware analysis systems. In this paper, by taking advantages of low false-positive rate of misuse detection and the ability of anomaly detection to detect zero-day malware, we propose a novel hybrid detection system based on a new open-source framework CuckooDroid, which enables the use of Cuckoo Sandbox's features to analyze Android malware through dynamic and static analysis. Our proposed system mainly consists of two parts: anomaly detection engine performing abnormal apps detection through dynamic analysis; signature detection engine performing known malware detection and classification with the combination of static and dynamic analysis. We evaluate our system using 5560 malware samples and 6000 benign samples. Experiments show that our anomaly detection engine with dynamic analysis is capable of detecting zero-day malware with a low false negative rate (1.16 %) and acceptable false positive rate (1.30 %); it is worth noting that our signature detection engine with hybrid analysis can accurately classify malware samples with an average positive rate 98.94 %. Considering the intensive computing resources required by the static and dynamic analysis, our proposed detection system should be deployed off-device, such as in the Cloud. The app store markets and the ordinary users can access our detection system for malware detection through cloud service. PMID- 26543719 TI - Vitamin D deficiency and fatigue: an unusual presentation. AB - Fatigue is a vague but common complaint that is poorly characterized by physicians as well as patients. While fatigue may result from a number of different etiologies, at the present time, a comprehensive approach to each patient with fatigue does not include routine measurement of serum vitamin D levels. A 61-year-old man was evaluated for excessive daytime fatigue. No features characteristic for depression, sleep apnea, or narcolepsy were present. A comprehensive work-up, including thyroid function tests and testosterone levels, did not reveal any abnormalities. However, serum 25-hydroxyvitamin D level was low, at 18.4 ng/mL. Vitamin D supplementation was initiated. At follow up in 3 and 12 months, the patient reported complete resolution of daytime fatigue, corresponding to an increase in his vitamin D levels. Possible mechanisms for clinical improvement include effects of vitamin D on components of inflammatory cascades, including tumor necrosis factor-alpha and prostaglandin D2, which result in decrease in central nervous system homeostatic sleep pressure. While more research is needed to determine if patients presenting with fatigue should be routinely screened for vitamin D deficiency, clinicians should consider obtaining vitamin D levels in patients with unexplained fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency. PMID- 26543720 TI - The challenge of durable brain control in patients with brain-only metastases from breast cancer. AB - The vast majority of patients with brain metastases from breast cancer have extracranial metastases, e.g., in the liver, lungs or bones, with serious impact on prognosis. Limited research has been performed on patients with brain-only disease. We analyzed patterns of treatment, brain control and survival in uni- and multivariate analyses. All 25 patients with brain-only disease were treated with radiotherapy (whole-brain radiotherapy (WBRT) with or without stereotactic radiotherapy/radiosurgery (SRS) or surgical resection) and most patients with systemic treatment later during the disease trajectory. Only a minority of patients remained free from brain progression at 1 year after their initial therapy, regardless of initial treatment approach (median brain progression-free survival 6.2 months). However, overall survival was significantly better after initial surgical resection/SRS as compared to upfront WBRT (median 24.1 and 5.2 months, respectively). For all patients combined, median survival was 11.7 months (2-year survival rate 28 %). Several prognostic factors for shorter survival were identified in multivariate regression analysis: lower KPS, triple-negative tumor, coordination deficit, older age, lack of upfront surgical resection or SRS, and lack of endocrine or HER2-directed therapy after brain metastases treatment. Although durable brain control and long-term survival beyond 5 years could be achieved in a subset of patients (largely after successful salvage), progression of brain metastases during the first year after diagnosis was common. Prognosis was influenced by patient-, disease- and treatment-related factors. PMID- 26543721 TI - Tautomerization, molecular structure, transition state structure, and vibrational spectra of 2-aminopyridines: a combined computational and experimental study. AB - BACKGROUND: 2-amino pyridine derivatives have attracted considerable interest because they are useful precursors for the synthesis of a variety of heterocyclic compounds possessing a medicinal value. In this work we aim to study both structural and electronic as well as high quality vibrational spectra for 2-amino 3-methylpyridine (2A3MP) and 2-amino-4-methylpyridine (2A4MP). RESULTS: Moller Plesset perturbation theory (MP2/6-31G(d) and MP2/6-31++G(d,p) methods were used to investigate the structure and vibrational analysis of (2A3MP) and (2A4MP). Tautomerization of 2A4MP was investigated by Density Functional Theory (DFT/B3LYP) method in the gas phase. For the first time, all tautomers including NH -> NH conversions as well as those usually omitted, NH -> CH and CH -> CH, were considered. The canonical structure (2A4MP1) is the most stable tautomer. It is 13.60 kcal/mole more stable than the next (2A4MP2). Transition state structures of pyramidal N inversion and proton transfer were computed at B3LYP/6 311++G(d,p). Barrier to transition state of hydrogen proton transfer is calculated as 44.81 kcal/mol. Transition state activation energy of pyramidal inversion at amino N is found to be 0.41 kcal/mol using the above method. Bond order and natural atomic charges were also calculated at the same level. The raman and FT-IR spectra of (2A3MP) and (2A4MP) were measured (4000-400 cm(-1)). The optimized molecular geometries, frequencies and vibrational bands intensity were calculated at ab initio (MP2) and DFT(B3LYP) levels of theory with 6-31G(d), 6-31++G(d,p) and 6-311++G(d,p) basis sets. The vibrational frequencies were compared with experimentally measured FT-IR and FT-Raman spectra. CONCLUSION: Reconsidering the vibrational analysis of (2A3MP) and (2A4MP) with more accurate FT-IR machine and highly accurate animation programs result in new improved vibrational assignments. Sophisticated quantum mechanics methods enable studying the transition state structure for different chemical systems. PMID- 26543722 TI - Rational diagnoses of diabetes: the comparison of 1,5-anhydroglucitol with other glycemic markers. AB - Diabetes mellitus (DM) is a frequently encountered disease with important morbidity and mortality. The aim of this study is to document the importance of 1,5-anhydroglucitol (1,5-AG) for the diagnosis of prediabetes and DM, as well as to compare the 1,5-AG with other glycemic markers in order to understand which one is the better diagnostic tool. Between April 2012 and December 2012, 128 participants enrolled in the study. Participants were split into five groups that are IFG, IGT, IFG+IGT, diabetic and control groups by their OGTT results. The diagnostic value of markers was compared by ROC (receiver operating characteristic) method. The mean serum 1,5-AG levels in the diabetic group (33.38 nmol/ml) were lower than, IFG (59.83 nmol/ml), IGT (54.44 nmol/ml), IFG+IGT (51.98 nmol/ml) and control groups (73.24 nmol/ml). When analyzed in the total study population serum 1,5-AG levels did not differ by gender significantly. When analyzed in the total study population, 1,5-AG correlates inversely with age significantly (p = 0.036). In subgroup analysis, in the control group, serum 1,5 AG level was also inversely correlated with age (p = 0.087). The best marker for the diagnosis of prediabetes and DM was fasting plasma glucose (FPG). 1,5-AG was not found to be effective for the diagnosis of DM. This study, contributes to our knowledge of the efficiency and cut-off values of 1,5-AG for the diagnosis of prediabetes and DM. In future, there is a need for larger studies with more standardized and commonly used measurement methods for 1,5-AG, in order to evaluate the efficiency of 1,5-AG for the diagnosis of prediabetes and DM. PMID- 26543723 TI - A boundary value approach for solving three-dimensional elliptic and hyperbolic partial differential equations. AB - In this article, the boundary value method is applied to solve three dimensional elliptic and hyperbolic partial differential equations. The partial derivatives with respect to two of the spatial variables (y, z) are discretized using finite difference approximations to obtain a large system of ordinary differential equations (ODEs) in the third spatial variable (x). Using interpolation and collocation techniques, a continuous scheme is developed and used to obtain discrete methods which are applied via the Block unification approach to obtain approximations to the resulting large system of ODEs. Several test problems are investigated to elucidate the solution process. PMID- 26543724 TI - Does analgesic overuse matter? Response to OnabotulinumtoxinA in patients with chronic migraine with or without medication overuse. AB - Chronic migraine affects 2 % of the population and has substantial impact on quality of life and considerable burden on healthcare resources. 50-80 % patients with chronic migraine have excessive consumption of analgesic medications. Withdrawal of analgesics is often advised before commencing preventive treatments. However, some headache experts recommend preventive treatments alongside analgesic withdrawal. 434 patients with chronic migraine attending the Hull Headache Clinic who received OnabotulinumtoxinA as preventive treatment were stratified to those with or without analgesic overuse. Data was collected through a dedicated headache diary and analysed for headache and migraine days reduction and for an increment in headache-free days in the month post treatment. The data shows no difference in the therapeutic outcome in patients with or without analgesic overuse with substantial reduction in headache and migraine days and an increment in headache-free days in both groups in a real-life clinical setting. OnabotulinumtoxinA is equally effective in patients with chronic migraine with or without analgesic overuse. PMID- 26543725 TI - Is agritourism eco-friendly? A comparison between agritourisms and other farms in Italy using farm accountancy data network dataset. AB - This paper presents the results of research regarding the environmental performances of Italian farms with agritourism compared with farms without agritourism. In Italy, agritourism is considered an agricultural activity and can only be performed by a farmer. Moreover, Italian national legislation forces the farmer to dedicate himself mainly to traditional farming, rather than to tourism activities. For this reason, environmental performances have been highlighted by analyzing only features and production systems of the farms. By utilizing the most frequent indicators used in studies regarding sustainability, the authors show how Italian agritourisms tend to develop more environmentally friendly agricultural methods, which have a positive impact on biodiversity, landscape and natural resources. The empirical analysis is based on the Italian FADN (Farm Accountancy Data Network) dataset. The European FADN was created to represent farms' technical and economic operation in the European Union and on which it drafts the agricultural and rural policies. The dichotomous structure of the dependent variable (presence or absence of agritourism at the farm) has a propensity for an assessment method based on Binary Response Model Regression. PMID- 26543726 TI - Dynamic graph cut based segmentation of mammogram. AB - This work presents the dynamic graph cut based Otsu's method to segment the masses in mammogram images. Major concern that threatens human life is cancer. Breast cancer is the most common type of disease among women in India and abroad. Breast cancer increases the mortality rate in India especially in women since it is considered to be the second largest form of disease which leads to death. Mammography is the best method for diagnosing early stage of cancer. The computer aided diagnosis lacks accuracy and it is time consuming. The main approach which makes the detection of cancerous masses accurate is segmentation process. This paper is a presentation of the dynamic graph cut based approach for effective segmentation of region of interest (ROI). The sensitivity, the specificity, the positive prediction value and the negative prediction value of the proposed algorithm are determined and compared with the existing algorithms. Both qualitative and quantitative methods are used to detect the accuracy of the proposed system. The sensitivity, the specificity, the positive prediction value and the negative prediction value of the proposed algorithm accounts to 98.88, 98.89, 93 and 97.5% which rates very high when compared to the existing algorithms. PMID- 26543727 TI - Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation. AB - BACKGROUND: Currently there is no reliable medical treatment for aortic regurgitation (AR). METHODS: Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks. Treatment-effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis. RESULTS: Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end-systolic diameter being significantly smaller (6.6 +/- 0.4 vs. 7.7 +/- 0.4 mm, respectively, p < 0.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23 +/- 0.08 vs. 2.16 +/- 0.05 mm, p < 0.01). Fractional shortening was improved by treatment (p < 0.05). Myocardial fibrosis was borderline decreased by treatment (p = 0.09). Akt was increased in treated compared to controls (p < 0.05). CONCLUSION: Sildenafil slightly inhibits LV remodeling and improves fractional shortening in rats with AR when treatment is initiated early. PMID- 26543728 TI - Differences between adolescents exhibiting moderate binging and non-binging eating behaviors. AB - Much research has been conducted to study the association between personality and eating disorders using clinical samples. However, less research has been done on personality variables in non-clinical cases of adolescents prone to binge eating. The purpose of this study is to compare a group of 53 adolescents without binge eating with a group of 28 adolescents with moderate binging behaviors and to investigate the relationship between personality traits and eating behaviors. All participants completed BES, STAY, EPQ-R, IVE and EDI-2. The results demonstrated that the group with moderate binging presented higher scores in state and trait anxiety, psychoticism, neuroticism, and impulsivity than the adolescents without binge eating. The second hypothesis of this research was to analyze the relationship between personality characteristics and eating behaviors. In the group of adolescents without binge eating both neuroticism and psychoticism correlated with ED symptomatology. Similarly extraversion, impulsivity and venturesomeness correlated with ED symptomatology. In the group of adolescents with moderate binge eating, there was an association of trait anxiety, extraversion, venturesomeness and empathy with ED symptomatology in university samples. The results of this study represent a new stimulus to thoroughly investigate those aspects of personality that may be predictive of ED symptomatology and to develop preventative strategies. It is our opinion that it is necessary to focus attention not only on clinical or non-clinical samples, but also on adolescents who could be considered at risk. PMID- 26543729 TI - Calcium supplementation improves clinical outcome in intensive care unit patients: a propensity score matched analysis of a large clinical database MIMIC II. AB - Observational studies have linked hypocalcemia with adverse clinical outcome in critically ill patients. However, calcium supplementation has never been formally investigated for its beneficial effect in critically ill patients. To investigate whether calcium supplementation can improve 28-day survival in adult critically ill patients. Secondary analysis of a large clinical database consisting over 30,000 critical ill patients was performed. Multivariable analysis was performed to examine the independent association of calcium supplementation and 28-day morality. Furthermore, propensity score matching technique was employed to investigate the role of calcium supplementation in improving survival. INTERVENTION: none. Primary outcome was the 28-day mortality. 90-day mortality was used as secondary outcome. A total of 32,551 adult patients, including 28,062 survivors and 4489 non-survivors (28-day mortality rate: 13.8 %) were included. Calcium supplementation was independently associated with improved 28-day mortality after adjusting for confounding variables (hazard ratio: 0.51; 95 % CI 0.47-0.56). Propensity score matching was performed and the after-matching cohort showed well balanced covariates. The results showed that calcium supplementation was associated with improved 28- and 90-day mortality (p < 0.05 for both Log-rank test). In adult critically ill patients, calcium supplementation during their ICU stay improved 28-day survival. This finding supports the use of calcium supplementation in critically ill patients. PMID- 26543730 TI - Enclosing the commons: reasons for the adoption and adaptation of enclosures in the arid and semi-arid rangelands of Chepareria, Kenya. AB - The adoption and adaptation of enclosures in the arid and semi-arid rangelands of sub-Saharan Africa is driven and sustained by a combination of factors. However, reviews indicate that these factors cannot be generalized, as they tend to be case specific. A study was therefore conducted to explore the history and reasons for enclosure establishment in Chepareria, a formerly degraded communal rangeland in north-western Kenya. While Vi-Agroforestry Organization accounting for 52.5 % was the main source of knowledge on enclosure establishment; it has now emerged that rangeland enclosures among the Pokot pastoral community existed prior to land management interventions by Vi- Agroforestry. Results indicated that there are three categories of enclosures which were established for boundary demarcation, provide grazing reserves, enable proper land management, facilitate crop cultivation in a pastoral setup and to curb land degradation. The role of self-trigger [accounting for most of the spontaneous enclosures (73.5 %)] indicates the continued establishment and expansion of areas under enclosure management as private land ownership accounting for 51.7 % of enclosure tenure continues to gain momentum in Chepareria. While rangeland enclosures in Chepareria were mainly established for boundary demarcation, to alleviate pasture scarcity and enable proper management of formerly degraded areas; they have facilitated land restoration and rehabilitation by increasing flexibility in land, fodder and livestock management amongst agro-pastoralists in Chepareria over the last three decades. To ensure that rehabilitated areas do not revert to their previously degraded state; technical interventions are needed to allow for a more intensive use of rangeland resources within enclosed areas. PMID- 26543731 TI - Stomach intestinal pylorus sparing surgery (SIPS) with laparoscopic fundoplication (LF): a new approach to gastroesophageal reflux disease (GERD) in the setting of morbid obesity. AB - The increase in the prevalence of obesity and gastroesophageal reflux disease (GERD) has paralleled one another. Laparoscopic fundoplication (LF) (Nissen or Toupet) is a minimally invasive form of anti-reflux surgery. The duodenal switch is a highly effective weight loss surgery with a proven record of long term weight loss success. However, fundoplication alone does not give satisfactory results when used for GERD in morbidly obese patients. Here we present a novel approach combining stomach intestinal pylorus sparing surgery (SIPS) with LF for morbidly obese patients with GERD. The data from patients who underwent the SIPS procedure along with LF in past year was retrospectively analyzed. The variables collected were age, sex, height, weight, intra-operative and post-operative complications, length of stay, operative time, and estimated blood loss. All revisions were excluded. Descriptive statistics such as mean and standard deviation were used to analyze the data. The total sample size of the study was 5 patients, with a mean age of 59.6 +/- 16.4 years, a mean weight of 292.1 +/- 73.6 lbs., and a mean body mass index (BMI) of 43.4 +/- 6.3. Weight loss patterns were the same as those without LF. All the 5 patients had resolution or improvement in their GERD symptoms within 6 months. SIPS with LF provides substantial and sustained weight loss and GERD resolution. Long term follow ups and further study on this novel surgical technique is recommended. PMID- 26543733 TI - 3D FEA of cemented glass fiber and cast posts with various dental cements in a maxillary central incisor. AB - This study aimed to analyse and compare the stability of two dental posts cemented with four different luting agents by examining their shear stress transfer through the FEM. Eight three-dimensional finite element models of a maxillary central incisor restored with glass fiber and Ni-Cr alloy cast dental posts. Each dental post was luted with zinc phosphate, Panavia resin, super bond C&B resin and glass ionomer materials. Finite element models were constructed and oblique loading of 100 N was applied. The distribution of shear stress was investigated at posts and cement/dentine interfaces using ABAQUS/CAE software. The peak shear stress for glass fiber post models minimized approximately three to four times of those for Ni-Cr alloy cast post models. There was negligible difference in peak of shear stress when various cements were compared, irrespective of post materials. The shear stress had same trend for all cement materials. This study found that the glass fiber dental post reduced the shear stress concentration at interfacial of post and cement/dentine compared to Ni-Cr alloy cast dental post. PMID- 26543732 TI - Stem cell transplantation therapy in Parkinson's disease. AB - Ineffective therapeutic treatments and inadequate repair ability in the central nervous system are disturbing problems for several neurological diseases. Fortunately, the development of clinically applicable populations of stem cells has provided an avenue to overcome the failure of endogenous repair systems and substitute new cells into the damaged brain. However, there are still several existing obstacles to translating into clinical application. Here we review the stem-cell based therapies for Parkinson's disease and discuss the potential advantages and drawbacks. We hope this review may provide suggestions for viable strategies to overcome the current technical and biological issues associated with the application of stem cells in Parkinson's disease. PMID- 26543735 TI - Ensifer-mediated transformation: an efficient non-Agrobacterium protocol for the genetic modification of rice. AB - While Agrobacterium-mediated transformation (AMT) remains the most widely used technique for gene transfer in plants, interest exists for the use of non Agrobacterium gene delivery systems due to freedom-to-operate issues that remain with AMT across several jurisdictions. In addition, the plant pathogenic mode of action of Agrobacterium tumefaciens significantly increases the costs to passage engineered cultivars through the regulatory process. Ensifer adhaerens (OV14) is a soil-related bacterium with the proven ability to genetically modify the model plant A. thaliana and the staple crop S. tuberosum (Wendt et al., Trans Res 21:567-578, 2012). While previous work was relevant for dicotyledonous species, in this study, the efficacy of Ensifer adhaerens (OV14)-mediated transformation (EMT) was determined on two japonica rice varieties, Curinga and Nipponbare, and the recalcitrant indica variety, IR64. The results indicated that E. adhaerens (OV14) exhibits infection efficiencies ranging between 50-70 %, 90-100 % and 90 95 % for Curinga, Nipponbare and IR64 respectively. Curinga and Nipponbare plants transformed with E. adhaerens (OV14) and A. tumefaciens (LBA4404 and EHA105) were regenerated achieving transformation efficiencies of 16 % and 26-32 % for Curinga and 7 and 4 % for Nipponbare respectively. Separately, the transformation of IR64 was only recorded via EMT (transformation efficiency ~1 %). Integration analyses conducted on 24 transgenic rice lines illustrated that T-DNA insertion occurred randomly throughout the rice genome for EMT (and AMT), with similar integration patterns in the rice genomic DNA observed for both bacterial species. PMID- 26543734 TI - Mechanism to control the cell lysis and the cell survival strategy in stationary phase under heat stress. AB - An array of stress signals triggering the bacterial cellular stress response is well known in Escherichia coli and other bacteria. Heat stress is usually sensed through the misfolded outer membrane porin (OMP) precursors in the periplasm, resulting in the activation of sigma(E) (encoded by rpoE), which binds to RNA polymerase to start the transcription of genes required for responding against the heat stress signal. At the elevated temperatures, sigma(E) also serves as the transcription factor for sigma(H) (the main heat shock sigma factor, encoded by rpoH), which is involved in the expression of several genes whose products deal with the cytoplasmic unfolded proteins. Besides, oxidative stress in form of the reactive oxygen species (ROS) that accumulate due to heat stress, has been found to give rise to viable but non-culturable (VBNC) cells at the early stationary phase, which is in turn lysed by the sigma(E)-dependent process. Such lysis of the defective cells may generate nutrients for the remaining population to survive with the capacity of formation of colony forming units (CFUs). sigma(H) is also known to regulate the transcription of the major heat shock proteins (HSPs) required for heat shock response (HSR) resulting in cellular survival. Present review concentrated on the cellular survival against heat stress employing the harmonized impact of sigma(E) and sigma(H) regulons and the HSPs as well as their inter connectivity towards the maintenance of cellular survival. PMID- 26543736 TI - Opsonic function of sialic acid specific lectin in freshwater crab Paratelphusa jacquemontii. AB - The sialic acid specific humoral lectin, Pjlec of the freshwater crab Paratelphusa jacquemontii was investigated for its opsonin function with rabbit erythrocyte as target cell for phagocytosis by the crab's hemocyte. The untreated or trypsin treated erythrocyte induced lectin response after challenge however failed when treated with neuraminidase evidently indicating glycan dependency for elicited immune response. Our observation of in vitro phagocytosis of the erythrocyte untreated or coated with serum, clarified serum appeared to be recognized and engulfed by hemocytes but when coated with isolated lectin Pjlec, the response was elicited. Moreover, with trypsin treated erythrocyte the response remained unchanged but neuraminidase or O-glycosidase treatment eliminated the response reaction. This suggested the sialic acid specific reaction of lectin with the erythrocyte and was essential for recognition to allow the lectin Pjlec to act as an opsonin. The flowcytometry observation affirmed the enhancement of phagocytosis by Pjlec coated hemocyte. The efficiency of in vitro hemolysis of Pjlec coated erythrocyte with hemocyte when compared to untreated erythrocyte with or without hemocyte also established the opsonic function of the lectin. The mechanism of phagocytosis and induction were dependent on specific recognition of the erythrocyte by the multivalent binding site of the lectin protein, and the elicitation of the immune response was a function of the sialoglycan surface. The pathway of the challenge suggested that after entry of nonself recognition by lectin was followed by induction and activation of phagocytosis by opsonic binding of the lectin. PMID- 26543738 TI - A rare complication following laparoscopic Roux & Y gastric bypass: intussusception-case report. AB - Obesity is a growing health problem in most parts of the world. Currently only proven long term effective treatment of obesity is bariatric surgery. Roux & Y gastric bypass together with sleeve gastrectomy are the most employed surgical techniques with acceptable metabolic and surgical complication rates. In this paper we would like to present an unexpected complication of Roux & Y gastric bypass: a retrograde intussusception located in the common limb 17 months after the surgery. As intussusception in adults usually originates from a leading point, there is no such an explanation following Roux & Y gastric bypass. PMID- 26543737 TI - No association between Helicobacter pylori infection and diabetes mellitus among a general Japanese population: a cross-sectional study. AB - Several case-control studies have reported that patients with diabetes mellitus (DM) had a higher prevalence of Helicobacter pylori infection than those without DM, but these findings remain equivocal. Additionally, there are few studies examining associations between East Asian CagA-positive H. pylori and DM. This cross-sectional study aimed to investigate whether H. pylori infection was a possible risk factor for DM in a general Japanese population. The study included 5165 subjects (1467 men, 3698 women) aged 35-69 years from the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. A urinary anti-H. pylori antibody was used to detect H. pylori infection. The medical history of physician-diagnosed DM was confirmed by self-administered questionnaire. The odds ratios (ORs) and their 95 % confidence intervals (CIs) for DM (current and former) were calculated using unconditional logistic regression analysis, adjusting for age, sex, educational status, alcohol use, smoking status, body mass index, energy intake, and physical activity. The prevalence of DM was 4.6 % (95 % CI 3.7-5.6 %) among 1878 participants with H. pylori infection and 3.2 % (2.6-3.8 %) among 3287 without the infection (p = 0.009). The crude, age adjusted, and multivariate-adjusted ORs for DM in those with the infection relative to those without were 1.47 (95 % CI 1.10-1.97), 1.02 (0.76-1.38), and 0.97 (0.71-1.32), respectively. We found a significantly higher DM prevalence among those with H. pylori infection than among those without. However, almost all the difference in prevalence could be explained by the older age of those infected. Our findings did not support an association between H. pylori infection and DM. PMID- 26543739 TI - Small-scale capture, transport and tank adaptation of live, medium-sized Scombrids using "Tuna Tubes". AB - The transport of live fish is a crucial step to establish fish culture in captivity, and is especially challenging for species that have not been commonly cultured before, therefore transport and handling methods need to be optimized and tailored. This study describes the use of tuna tubes for small-scale transport of medium-sized pelagic fish from the Scombridae family. Tuna tubes are an array of vertical tubes that hold the fish, while fresh seawater is pumped up the tubes and through the fish mouth and gills, providing oxygen and removing wastes. In this study, 19 fish were captured using rod and line and 42 % of the captured fish were transported alive in the custom-designed tuna tubes to an on shore holding tank: five mackerel tuna (Euthynnus affinis) and three leaping bonito (Cybiosarda elegans). Out of these, just three (15.8 % of total fish) acclimatized to the tank's condition. Based on these results, we discuss an improved design of the tuna tubes that has the potential to increase survival rates and enable a simple and low cost method of transporting of live pelagic fish. PMID- 26543740 TI - Can atlas spina bifida-occulta be a cause of cervicogenic headaches? AB - Cervicogenic headaches are a nosologic entity recently recognized. In our common practice, we have noticed a relative frequency of the atlas spina-bifida occulta during the brain CT scan realized for headaches without cranio-encephalic causes or any other anomaly of the upper cervical region. The aim of this study was to determine a possible connection between cervicogenic headaches (CEH) and atlas spina-bifida occulta. A 2 years prospective and descriptive study in 20 black patients having an atlas spina-bifida occulta diagnosed with a brain CT scan. The mean age of the patients was 43.17 +/- 18.35 years (extremes: 24 and 72 years). A light female predominance was noticed (sex-ratio = 1.5). The frequency of symptomatic spina-bifida was 1.72 % (17 cases). The mean age at onset was 31.84 years. The pain was sub-occipital in 14 cases, occipital in 8 cases, bilateral in 12 cases and unilateral in 5 cases. The mean duration of the attacks was 72 +/- 24 h and the pain intensity was moderate (16 cases); mean and range were 3.6 and 3-6. The frequency of attacks varied between 1 per 7 months (n = 2) and 2 per week (n = 1) in those with non-daily headache. One attack per 5-7 weeks was the most commonly occurring attack frequency. The pain was reproduced by the pressure of the occipital region or upper cervical in 15 cases. The mean number of criteria was five and there was a strong positive correlation between criteria and CEH (chi (2) = 45.57; V = 0.62). The associated signs were photophobia and nausea in one case each. Indomethacin, Ergotamine and/or Sumatriptan were without any antalgic effect in 16 cases. Pain ceased after an anesthetic blockade of C2 (16 cases). The results show that atlas spina-bifida occulta is not involved in CEH pure form genesis. On a small sample, the atlas spina-bifida seems to be a cause of CEH associated with headache and disorders of the neck. PMID- 26543741 TI - Acceptability of mental health stigma-reduction training and initial effects on awareness among military personnel. AB - The purpose of this paper is to report on the development of a mental health stigma reduction toolkit and training, and the acceptability and level of stigma awareness following the stigma-reduction training for military personnel. The overall aims of the training were to provide discussion tools highlighting the experiences of Marines seeking help for stress concerns, improve communication between leaders and their Marines around the issue of help seeking, and familiarize Marines with behavioral health treatment. Senior enlisted leaders and officers (N = 52) from a Marine Corps battalion participated in a pretest, 2-h stigma-reduction training and immediate posttest. Acceptability of the training was measured by querying participants about the usefulness and helpfulness of the training among other factors, and stigma awareness was measured with 10 items about mental health stigma. The stigma-reduction training and materials were well accepted by participants. In addition, there was a significant improvement in four of ten stigma-reduction awareness concepts measured before and immediately after the training, which included an increase in agreement that mental health treatments are usually effective in reducing stress reactions [t(51) = -3.35, p = 0.002], and an increase in disagreement that seeking counseling after a deployment will jeopardize future deployments [t(51) = -3.05, p = 0.004]. Level of agreement with several statements including those regarding perceptions of invincibility, and malingering, among others, did not change significantly after the training. The stigma-reduction training containing educational and contact strategies was highly acceptable to the leaders and may have promise for initially dispelling myths associated with seeking help for stress concerns among military service members; however, results indicate that there is clearly more work to be done in combatting stigma. PMID- 26543743 TI - Korobov polynomials of the third kind and of the fourth kind. AB - The first degenerate version of the Bernoulli polynomials of the second kind appeared in the paper by Korobov (Math Notes 2:77-19, 1996; Proceedings of the IV international conference modern problems of number theory and its applications, pp 40-49, 2001). In this paper, we study two degenerate versions of the Bernoulli polynomials of the second kind which will be called Korobov polynomials of third kind and of the fourth kind. Some properties, identities, recurrence relations and connections with other polynomials are investigated by using umbral calculus. PMID- 26543742 TI - Biologic-free remission by orthopaedic surgery in non-responder to infliximab for rheumatoid arthritis. AB - The aim of this study was to investigate remission and biologic-free remission after orthopaedic surgery and related clinical factors in non-responder to infliximab for rheumatoid arthritis (RA). We analyzed 74 patients who were treated with 3 mg/kg infliximab and methotrexate and underwent orthopaedic surgery after non-responder to infliximab with disease activity score (DAS) 28 (CRP) of >=3.2. The rates of remission and biologic-free remission at 52 weeks after orthopaedic surgery were investigated and the clinical factors related to remission and biologic-free remission were analyzed by logistic regression and receiver-operating characteristic analyses. The rates of total remission and biologic-free remission were 37/74 (50 %) and 9/74 (12.2 %), respectively. Regarding orthopaedic surgery, the rates of remission and biologic-free remission were 25/38 (65.8 %) and 7/38 (18.4 %) for synovectomy, 7/20 (35 %) and 0/20 (0 %) for arthroplasty, and 5/16 (31.3 %) and 2/16 12.5) for others including spine surgery and foot surgery. DAS28(CRP) at baseline was significantly related to both remission and biologic-free remission. Prednisolone was negatively associated with remission, and DAS28(CRP) was related to biologic-free remission by logistic regression analyses. DAS28(CRP) below 3.7 was cutoff point for acquiring biologic-free remission of non-responder to infliximab after orthopaedic surgery. Therefore orthopaedic surgery may be effective to obtain remission or biologic-free remission in RA patients treated with biologics. PMID- 26543744 TI - Superficial temporal artery-to-middle cerebral artery bypass surgery for middle cerebral artery stenosis in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. AB - Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare hereditary small vessel disease. Ischemic events are the main clinical manifestation of this condition. Here, we present a case in which superficial temporal artery-to-middle cerebral artery anastomosis was performed in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy who developed cerebral infarctions caused by severe middle cerebral artery stenosis. Cerebral blood flow and cerebrovascular reactivity were effectively improved using double anastomoses. To our knowledge, surgical revascularization for patients with this condition has not yet been described in the literature. Superficial temporal artery-to-middle cerebral artery anastomosis is effective for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy who show marked regional cerebral hypoperfusion. PMID- 26543745 TI - CXCL1 is elevated in the urine of bladder cancer patients. AB - Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Recently, several studies have linked CXCL1 expression to bladder cancer (BCa). In this study, we aimed to determine if increased levels of urinary CXCL1 were found in BCa patients. Voided urines from 86 subjects, cancer subjects (n = 43), non-cancer subjects (n = 43) were analyzed. The protein concentration of CXCL1 was assessed by enzyme-linked immunosorbent assay (ELISA). CXCL1 concentration level was normalized using urinary protein and urinary creatinine concentrations. We used the area under the curve of a receiver operating characteristic (AUROC) to investigate the performance of CXCL1 in detecting BCa. Mean urinary concentrations of CXCL1 were significantly higher in subjects with BCa compared to subjects without BCa (179.8 +/- 371.7 pg/mg of creatinine vs. 28.2 +/- 71.9 pg/mg, respectively p = 0.0009). Urinary CXCL1 possessed a sensitivity of 55.81 %, specificity of 83.72 %, positive predictive value of 77.42 %, negative predictive value of 65.46 %, and an overall accuracy of 69.77 % (AUROC: 0.7015, 95 % CI 0.5903-0.8126). These results indicate that CXCL1 is elevated in BCa when compared to non-cancer subjects, but lacks robustness as a standalone urinary biomarker. Additional studies into CXCL1 may shed more light on the role of CXCL1 in BCa tumorigenesis as well as ramifications of therapeutically targeting CXCL1. PMID- 26543748 TI - Youth development in India: does poverty matter? AB - This paper explores the differentials in youth development patterns determined by the economic condition of the household in India. The wealth index is used to glean youth development differentials in the different economic categories of the household. The findings suggest that youth from the bottom 20 per cent (poorest) of households are deprived in education, employment, labour force and are not working currently compared to youth from the middle and rich households. The states differ in youth development patterns (employment, appropriate education, skill development and awareness about health). There are more working youth among poor households than among rich households in India. Female youth are more disadvantaged compared to male youth and it is the same with the rural-urban distribution of youth. This paper concludes that the various economic categories/wealth index (poorest, poorer, middle, richer and richest) directly determine the pattern of youth development in India. PMID- 26543747 TI - Sales of macrolides, lincosamides, streptogramins, and amoxicillin/clavulanate in the in- and outpatient setting in 10 European countries, 2007-2010. AB - Monitoring the use of antibiotics is relevant due to the public health impact of microbial resistance, adverse effects, and costs. We present data on the consumption of macrolides, lincosamides, streptogramins and amoxicillin/clavulanate (AMC) between 2007 and 2010 in the in-and outpatient healthcare setting in 10 European countries provided by IMS Health. Antibiotics were classified according to the anatomical therapeutic chemical classification and consumption was expressed in defined daily doses/1000 inhabitants/day (DIDs). We analysed the number of prescriptions by diagnostic codes between 2008 and 2010, based on the International Classification of Diseases, 10th revision (ICD 10). These ICD-10 codes were grouped into four main categories: respiratory infections, genitourinary infections, other infections and other diagnoses. In 2010, the consumption of macrolides and lincosamides ranged from 0.45 DIDs (Sweden) to 5.46 DIDs (Italy), and from 0.04 DIDs (Denmark) to 1.00 DID (Germany), respectively. Streptogramins were available in France, Germany, Italy, Norway, Spain and United Kingdom with a consumption of <0.001 DID exclusively in the hospital setting. The consumption of AMC ranged from <0.001 DIDs (Norway) to 11.67 DIDs (Spain). During the study period, the consumption of macrolides decreased, the consumption of AMC increased in most of European countries, and lincosamides varied very slightly. Macrolides and AMC were mainly prescribed for respiratory infections in all countries but United Kingdom, where most of the prescriptions were assigned to diagnostic codes not clearly related with an infection. Lincosamides were prescribed for the respiratory infections and other infections groups. There was a wide inter-country variability in the percentage of the prescriptions assigned to each of the diagnostic categories. The inter country differences in the consumption of these antibiotics and their prescription by diagnostic categories point to an inappropriate use of antibiotics. PMID- 26543746 TI - Understanding drugs in breast cancer through drug sensitivity screening. AB - With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens. PMID- 26543749 TI - ELISA-based detection of gentamicin and vancomycin in protein-containing samples. AB - BACKGROUND: Orthopaedic implant infections are treated by surgical debridement, systematic antibiotic treatment or local antibiotic treatment with antibiotic loaded beads. Currently antibiotic concentrations in wound exudate, serum, urine or tissue samples are determined with HPLC or fluorescent spectrometric assays. Both methods are heavily influenced due to proteins in the samples. QUESTIONS/PURPOSES: Is ELISA capable to detect gentamicin and vancomycin in protein-containing samples like serum and wound exudate. METHODS: Two specific competitive ELISA-assays were set-up to detect either gentamicin or vancomycin in protein-rich samples. An antibiotic-BSA hapten was generated as a coatable antigen and commercially available antibodies were applied for downstream immunodetection. RESULTS: The developed ELISAs perform at a detection range of 2 500 ng/ml gentamycin and 20-5000 ng/ml vancomycin. Both ELISAs were capable of detecting these antibiotics in human serum and wound exudate without being compromised by the presence of proteins. We did not detect cross-reactivity for gentamicin in the vancomycin ELISA or vice versa. CONCLUSIONS: The antibiotic ELISAs detect gentamicin and vancomycin at low concentrations in protein-rich samples and they can be used as a high throughput and cost-effective alternative for chromatographic or fluorescent methods. CLINICAL RELEVANCE: These ELISAs can be used to detect very low gentamicin or vancomycin concentrations in clinical samples or assess novel orthopaedic antibiotic release systems in in vitro and in vivo studies. PMID- 26543750 TI - Mammography screening in less developed countries. AB - Less developed countries (LDCs) are struggling with an increasing burden of breast cancer. It is important to identify what interventions might be most effective and feasible in reducing overall breast cancer mortality in a resource constrained settings. Mammography screening (MS) utilized in developed countries cannot be equally applied to LDCs. We provide a summary of the status of existing and past MS program attempts in LDCs, and try to determine the prerequisites under which any developing country is ready to benefit from a MS program. We make the case for a "mixed" portfolio of tools to reduce breast cancer mortality with MS reserved only for those sub-populations that meet the criteria. We hope our review will provide a background for policy makers to apply rigorous criteria before attempting to implement costly MS program and before judiciously evaluating additional competed programs in their countries. PMID- 26543751 TI - 5p13.3p13.2 duplication associated with developmental delay, congenital malformations and chromosome instability manifested as low-level aneuploidy. AB - Recent developments in molecular cytogenetics allow the detection of genomic rearrangements at an unprecedented level leading to discoveries of previously unknown chromosomal imbalances (zygotic and post-zygotic/mosaic). These can be accompanied by a different kind of pathological genome variations, i.e. chromosome instability (CIN) manifested as structural chromosomal rearrangements and low-level mosaic aneuploidy. Fortunately, combining whole-genome and single cell molecular cytogenetic techniques with bioinformatics offers an opportunity to link genomic changes to specific molecular or cellular pathology. High resolution chromosomal SNP microarray analysis was performed to study the genome of a 15-month-aged boy presented with developmental delay, congenital malformations, feeding problems, deafness, epileptiform activity, and eye pathology. In addition, somatic chromosomal mutations (CIN) were analyzed by fluorescence in situ hybridization (FISH). Interstitial 5p13.3p13.2 duplication was revealed in the index patient. Moreover, CIN manifested almost exclusively as chromosome losses and gains (aneuploidy) was detected. Using bioinformatic analysis of SNP array data and FISH results, CIN association with the genomic imbalance resulted from the duplication was proposed. The duplication was demonstrated to encompass genes implicated in cell cycle, programmed cell death, chromosome segregation and genome stability maintenance pathways as shown by an interactomic analysis. Genotype-phenotype correlations were observed, as well. To the best our knowledge, identical duplications have not been reported in the available literature. Apart from genotype-phenotype correlations, it was possible to propose a link between the duplication and CIN (aneuploidy). This case study demonstrates that combining SNP array genomic analysis, bioinformatics and molecular cytogenetic evaluation of somatic genome variations is able to provide a view on cellular and molecular pathology in a personalized manner. Therefore, one can speculate that similar approaches targeting both interindividual and intercellular genomic variations could be useful for a better understanding of disease mechanisms and disease-related biological processes. PMID- 26543752 TI - Opportunities and challenges of indigenous biotic weather forecasting among the Borena herders of southern Ethiopia. AB - The practical utilization of available modern as well as traditional weather forecasting systems builds herders' resiliency capacity to climatic shocks. The precision and reliability of the forecasting system determines its creditability and acceptance by the users to be proactive in the decisions they make based on the forecasted information. It has been postulated that traditional weather forecasting systems are becoming less reliable due to repeated faulty forecasts. The study assesses the current status of the Borana traditional weather forecasting system and how traditional experts make weather forecasts based on biotic indicators such as intestinal readings, changes in plant and animal body languages. Questionnaire survey, field observations, focus group discussions and interviews with relevant key informants were employed to obtain data. Collected field data was compared with National Metrological Service Agency instrumental data for consistency. Results reveal that herders made short term weather forecasts using intestinal readings, and observed changes in plant and animal body languages. The study shows the extent how public confidence in the accuracy of indigenous weather forecasting skills has been gradually eroded overtime due to faulty forecasts. The precision and credibility of the traditional weather forecast steadily declined and led to repeated faulty predictions. Poor documentation, oral based knowledge transfer system, influence of religion and modern education, aging and extinction of traditional experts were identified as the major causes undermining the vitality of traditional climate forecast. Traditional weather foresting knowledge and skill could have some utility and also serve as a starting point to scientifically study the relationship between various signs and implied climatic events. This article recommends before traditional Borana weather forecasting system completely disappears, a remedial action should be carried out to rescue this long established wisdom, knowledge and skill and maximize the benefits from what works well. The forecast needs of herders could be rendered by a combination of modern and traditional weather forecasting services. Further research is required to explore possible area of complementarity between the modern and traditional forecasting systems for improved efficiency and effectiveness in predictability, dissemination and advice. PMID- 26543753 TI - Low carbon transportation in Thailand: CO2 mitigation strategy in 2050. AB - Nationally Appropriate Mitigation Actions (NAMAs) involve the collaboration on reduction of greenhouse gas (GHG) emissions in developing countries with suitable countermeasures relevant to the state of technological and economic conditions prevalent in the country. This study proposes appropriate GHG countermeasures in Thai transport NAMAs, which are based on the implementation of transport demand management, modal shift, fuel switching, and advanced technologies in the timeframe between 2005 and 2050. Furthermore, this study considers the impacts of CO2 mitigation through the proposed countermeasures on energy security and GHG emissions. Results of analyses on low carbon transportation are also useful to other developing countries. Finally, the concept of marginal abatement cost is employed to investigate cost-effective mitigation countermeasures. PMID- 26543754 TI - Modulatory effect of protocatechuic acid on cadmium induced nephrotoxicity and hepatoxicity in rats in vivo. AB - INTRODUCTION: This study sought to investigate the effect of protocatechuic acid (PCA); a phenolic compound readily available in most plant foods on cadmium induced nephrotoxicity and hepatoxicity in rats. CASE DESCRIPTION: Thirty six adult male rats weighing about 150-160 g were acclimatized for 2 weeks and subsequently divided into six groups: Group 1 rats received normal saline (control group), group 2 rats were administered 5 mg Cd/kg body weight in form of solution orally (induced group), groups 3 and 4 received cadmium solution and different doses of PCA (10 and 20 mg/kg body weight) respectively, while groups 5 and 6 were the normal rats administered different doses of PCA (10 and 20 mg/kg) respectively in an experiment that lasted for twenty one days. The animals were sacrificed, the blood was collected and the serum was subsequently prepared. Furthermore, the liver was excised, homogenized and centrifuged to obtain the tissue homogenate used for the analyses. The serum was used for the determination of the total protein, urea, creatinine and uric acid levels while the liver homogenate was used for the estimation of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). DISCUSSION AND EVALUATION: The result revealed that total protein level was reduced in cadmium induced toxicity rat group which was elevated upon treatment with PCA. Conversely, the elevated levels of urea, uric acid and creatinine in cadmium induced toxicity kidney rats were significantly (p < 0.05) reduced in PCA treated groups. Similarly, marked elevation in the ALT, AST and ALP activity were observed in cadmium induced toxicity rat group when compared with the control group. However, significant (p < 0.05) decrease in ALT, AST and ALP activity were noticed in groups administered different doses of PCA. CONCLUSIONS: The results from this study suggest that PCA may protect against cadmium-induced toxicity in the kidney and liver. PMID- 26543755 TI - Susceptibility variation to different entomopathogenic nematodes in Strategus aloeus L (Coleoptera: Scarabaeidae). AB - Strategus aloeus L (Coleoptera: Scarabaeidae), known as "Little bull" or oil palm "chiza" is a limiting pest in palm plantation in Cesar Colombia. Its management is based on pesticide use or old palm removal in renewal lots. Therefore, other alternatives are being sought out. Entomopathogenic nematodes isolated from the Colombian Andean region were evaluated. Under laboratory conditions S. aloeus third instar larvae exposure to 160 infective juveniles (IJs) per/cm(2) Steinernema sp3 JCL027, S. feltiae SCT125, S. websteri JCL006, S. colombiense SNI0198, Heterorhabditis bacteriophora HNI0100, H. bacteriophora HASA702, H. indica SL0708 (n = 20) was evaluated under a completely randomized design. The experiment was repeated three times on different dates. Significant differences were observed (F = 11.127, df = 7. 24, p = 0.0054), registering mortality between 3 and 14 days. Steinernema sp3 JCL027 was the strain producing the highest mortality rate (19.3 +/- 8 %), followed by H. bacteriophora HNI0100 (5.2 +/- 9 %). Thus, we evaluated Steinernema sp3 JCL0270 using a randomized design at 0, 160, 290, 420, 550, 680, 810 IJs/cm(2) (n = 12). The experiment was repeated three times on different dates. Significant differences were found among treatments (44 +/- 5 %, F = 14.676; df = 6. 21, p = 0.001), with 680 IJs/cm(2) producing the highest mortality followed by 810 IJs/cm(2) (22 +/- 5 %). In conclusion, this alternative must be further explored in search of pesticide use and cost reduction, in addition to young palm loss in a plantation. PMID- 26543756 TI - Disrupted normal ingestion during glucose intake modulates glucose kinetics in humans. AB - This study aims to reveal the importance of chemical senses in glucose kinetics and autonomic nervous activity by imposing interventions during glucose intake. The glucose-loading test was applied to seven healthy individuals. Three successive oral glucose-loadings induced a gradual downward shift in the blood glucose curves (BGC) together with increased salivary alpha-amylase activity (s AMY) and positively correlated with satisfaction scores. On the other hands, adding a pleasant flavor given during the third trial increased the BGC to the same level as that during the first loading with decreased s-AMY value. Direct intragastric delivery of glucose or clipping the nose induced a downward shift in both BGC and serum insulin response curves (IRC), resulting in a decrease of the area under the BGC, positively correlated with the area under the IRC and satisfaction scores, respectively. The present study suggests that disrupted normal ingestion during glucose intake modulates glucose kinetics along with increased s-AMY values, indicating enhanced sympathetic nervous activity and favorable chemical senses are important in maintaining glucose kinetics. PMID- 26543757 TI - Effect of oral glucocorticoid intake on autonomic cardiovascular control. AB - This study analyzed baroreflex sensitivity, heart rate and systolic blood pressure variabilities during an oral 1 week administration of prednisone. This study examined the hypothesis that prednisone might change both systolic blood pressure level and baroreflex sensitivity. Twelve physically active male subjects participated to a double-blind, randomized cross-over study consisting of two 1 week periods of treatment separated by a 4-week drug-free washout period: placebo (PLA) or prednisone (PRED). Trials were performed by each subject four times on the second (D2) and seventh (D7) day of each treatment period. ECG and blood pressure were continuously recorded to compute heart rate variability, systolic blood pressure variability and baroreflex sensitivity components with the smoothed pseudo Wigner Ville distribution and baroreflex analysis. Following D2 prednisone treatment, both HR (PLA: 60.8 +/- 10.5 vs. PRED: 65.8 +/- 9.1 beats min(-1), p = 0.008) and low frequency component of systolic blood pressure variability (D2: 3.09 +/- 0.19 vs. D7: 2.34 +/- 0.19, p < 0.041) increased whereas other components did not change. Over 7 days of treatment, LF-SBP amplitude increased (D2: 2.71 +/- 0.89 vs. D7: 3.87 +/- 0.6 mmHg, p = 0.037). A slight increase in both HR and LF-SBPV were observed suggesting a potential sympathetic cardiovascular stimulus. Although we found a significant effect of the 1-week prednisone treatment on heart rate and low frequency power of systolic blood pressure variability, we reported neither an increase in the systolic blood pressure level nor a decrease in the baroreflex sensitivity. Therefore, the fragility of our results cannot support a deleterious effect of 1-week administration of prednisone on the autonomic cardiovascular control which might be involved in cardiovascular diseases. PMID- 26543758 TI - Validation of the electronic Holistic Needs Assessment. AB - Macmillan Cancer Support UK have developed an electronic Holistic Needs Assessment (eHNA) to: (1) help people living with cancer express all their needs, (2) help those helping them better target support. eHNA consists of 48 items each ranked from zero (no problem) to 10. There has been no psychometric analysis of this tool and so its validity and reliability are untested. The aim of this study was to evaluate the psychometric properties of the eHNA by examining its construct validity. Objectives were to (a) test whether the eHNA measured holistic concerns and (b) analyse the factor structure of the eHNA. Objectives were achieved through a secondary analysis of 5421 responses to eHNA using concurrent application of Rasch analysis and principal component analysis. All the items bar one fit with the Rasch rating model and were equivalently important to people. Differential item functioning was evident according to whether people were described as curative or not. A 12-factor solution explained 46 % variance. Of this the emotional/spiritual factor explained the most variance accounting for 15 %. The eHNA was internally consistent and conceptually coherent with the construct of holistic needs assessment. Clinical focus is best directed to the individual items highlighted by the patient except where patients check too many problems for the clinician to accurately prioritise. In these cases only, the emotional/spiritual factor may help identify appropriate clinical action. Strengths and weaknesses of the analyses are discussed, particularly in relation to 'at risk' subsamples such as those classified as non-curative. PMID- 26543759 TI - Realities in cost-effectiveness analyses: a study of castration-resistant prostate cancer patients using a medical claims database. AB - Previous cost-effectiveness analyses (CEAs) of abiraterone for castration resistant prostate cancer (CRPC) patients have not shown favorable results for this new drug. These CEAs were generally conducted based on models used in clinical trials, where comparisons were made with patients given placebos. However, details on any other therapies provided to the comparison groups were not analyzed. These additional therapies should be considered when conducting CEAs to ensure better applications to clinical practice and policymaking. The objective of this study was to elucidate the actual therapies provided to CRPC patients using real-world claims data. We obtained anonymized computerized health care claims data of Japanese prostate cancer patients from the Japan Medical Data Center. This database comprises data from more than 2.5 million insured persons aged below 75 years from over 50 companies between January 2005 and June 2013. From among the prostate cancer patients, we identified CRPC patients as those who had been administered docetaxel, and further investigated their treatments and health care costs. Health care costs were estimated using a regression model accounting for variations in inpatient care, chemotherapies, death, and age. We identified 2138 prostate cancer patients, 36 of whom had been administered docetaxel. We excluded patients diagnosed with other cancers, resulting in a final sample of 18 cases. Of these, 66.7 % were administered other types of chemotherapy, which had not been considered in the control groups in most previous CEAs. We estimated mean health care costs for CRPC to be approximately US$952 per patient per month, and found that these costs were significantly affected by inpatient care and chemotherapy use. Actual therapies include a variety of treatments for CRPC patients, including various types of chemotherapy. Our study estimated health care costs based on real-world claims data. This study contributes to future CEAs by not only providing an estimate of health care costs for these patients, but also demonstrating that the actual therapies provided to comparison groups should be considered when conducting CEAs. PMID- 26543760 TI - Eribulin monotherapy improved survivals in patients with ER-positive HER2 negative metastatic breast cancer in the real world: a single institutional review. AB - Despite being routinely prescribed worldwide for several years, data regarding the safety, efficacy, and survival benefit of eribulin in clinical settings for the treatment of metastatic breast cancer (MBC) are limited. This retrospective observational study investigated the survival benefit of eribulin compared with conventional chemotherapy regimens in Japanese women with MBC. Women with estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) MBC, including unresectable locally advanced breast cancer, treated at a single institution were included in this study. The primary efficacy measure assessed overall survival (OS), and safety was evaluated as the number of grade 3 and 4 adverse events. Of the 293 patients analyzed, 66 received eribulin (eribulin arm) and 227 received conventional chemotherapeutic agents excluding eribulin (noneribulin arm). The median OS from MBC diagnosis in the eribulin arm was 72.1 months (95 % CI 13.3-168.3) compared with 43.3 months (95 % CI 9.1 202.0) in the noneribulin arm [hazard ratio (HR): 0.67, 95 % CI 0.47-0.96; P = 0.025]. No significant differences were noted in OS between eribulin used as a first-/second-line or third-/>third-line treatment for MBC. No patient discontinued eribulin therapy due to AEs. In the eribulin arm, grade 4 neutropenia and grade 3 febrile neutropenia were observed in 8 (12.1 %) and 4 (6.1 %) patients, respectively. Eribulin therapy has a survival benefit in Japanese women with ER+/HER2- MBC in routine clinical practice, with no unexpected grade 3/4 AEs. Interestingly, eribulin might be beneficial as any line therapy for ER+/HER2- MBC. PMID- 26543761 TI - Global methaemoglobinaemia research output (1940-2013): a bibliometric analysis. AB - Bibliometric studies, which involve the use of statistical methods, are increasingly being used for research assessment. A bibliometric analysis was conducted to evaluate the publication pattern of methaemoglobinaemia research output at the global level based on the Scopus database. We analysed selected documents with "methemoglobinemia", or "methaemoglobinaemia" as a part of the title and reported the following parameters: trends of publication output, country of publication, journal pattern, collaborative measures, citations pattern, and institute productivity. A total of 1770 articles were published worldwide. The time trend for the number of articles showed an increase after 2000. The highest number of articles related to methaemoglobinaemia was from the USA (24.8 %), followed distantly by the UK (4.5 %), India (3.7 %), and France (3.7 %). No data related to methaemoglobinaemia were published from 152 countries. The total number of citations at the date of data collection was 10,080, with an average of 5.7 citations per document. The USA and UK had the highest h-index of 31 and 14, respectively, and six countries had an h-index of 9 14. It is notable that Canada was ranked eighth in the number of publications but fourth in h-index and India was ranked third in the number of publications but eighth in h-index. Furthermore, Canada produced the most internationally collaborated papers out of the total number of publications for each country (16.1 %), followed by the UK (13.9 %). This bibliometric analysis provides data contributing to a better understanding of the methaemoglobinaemia research field. The number of publications on methaemoglobinaemia increased significantly after 2000. The USA was the most productive country as measured by total publications. The USA and UK achieved the highest h-index in the field of methaemoglobinaemia research, signifying a higher quality of research than other countries. PMID- 26543762 TI - Molecular characterization of nosocomial Clostridium difficile infection in pediatric ward in Iran. AB - Clostridium difficile is recognized as a major cause of nosocomial acquired antibiotic-associated diarrhea and pseudomembranous colitis. It is a significant financial burden on modern healthcare resources. This study aimed to assess the molecular characterization of C. difficile strains isolated from children under 5 years old suffered from nosocomial diarrhea. One hundred diarrheic and 130 non diarrheic fecal samples were collected from pediatrics less than 5 years old. Samples were cultured and C. difficile isolates were subjected to the PCR technique to study the distribution of ribotypes of C. difficile using P3 and P5 primers. Fifty-two out of 100 samples (52 %) were positive for C. difficile. The prevalence of bacterium in healthy children was 4.61 %. Total prevalence of C. difficile in diarrheic girls and boys were 48.9 and 54.7 %, respectively. Thirteen to twenty-four month age children had the highest prevalence of C. difficile. The most commonly detected ribotypes in the C. difficile isolates of Iranian pediatrics were RT027 (11.52 %), R1 (9.61 %) and R13 (7.68 %). The ribotypes of all of the six bacterial isolates of healthy children was not diagnosed. According to the presence of C. difficile and R27 ribotype, a continued genotype surveillance of this bacterium is necessary to monitor changes in the prevalence of certain strains and to identify the emergence of new strains that could affect future vaccine strategies. PMID- 26543763 TI - MicroBlaze implementation of GPS/INS integrated system on Virtex-6 FPGA. AB - The emphasis of this paper is on MicroBlaze implementation of GPS/INS integrated system on Virtex-6 field programmable gate array (FPGA). Issues related to accuracy of position, resource usage of FPGA in terms of slices, DSP48, block random access memory, computation time, latency and power consumption are presented. An improved design of a loosely coupled GPS/INS integrated system is described in this paper. The inertial navigation solution and Kalman filter computations are provided by the MicroBlaze on Virtex-6 FPGA. The real time processed navigation solutions are updated with a rate of 100 Hz. PMID- 26543764 TI - A model for solving the prescribed burn planning problem. AB - The increasing frequency of destructive wildfires, with a consequent loss of life and property, has led to fire and land management agencies initiating extensive fuel management programs. This involves long-term planning of fuel reduction activities such as prescribed burning or mechanical clearing. In this paper, we propose a mixed integer programming (MIP) model that determines when and where fuel reduction activities should take place. The model takes into account multiple vegetation types in the landscape, their tolerance to frequency of fire events, and keeps track of the age of each vegetation class in each treatment unit. The objective is to minimise fuel load over the planning horizon. The complexity of scheduling fuel reduction activities has led to the introduction of sophisticated mathematical optimisation methods. While these approaches can provide optimum solutions, they can be computationally expensive, particularly for fuel management planning which extends across the landscape and spans long term planning horizons. This raises the question of how much better do exact modelling approaches compare to simpler heuristic approaches in their solutions. To answer this question, the proposed model is run using an exact MIP (using commercial MIP solver) and two heuristic approaches that decompose the problem into multiple single-period sub problems. The Knapsack Problem (KP), which is the first heuristic approach, solves the single period problems, using an exact MIP approach. The second heuristic approach solves the single period sub problem using a greedy heuristic approach. The three methods are compared in term of model tractability, computational time and the objective values. The model was tested using randomised data from 711 treatment units in the Barwon-Otway district of Victoria, Australia. Solutions for the exact MIP could be obtained for up to a 15-year planning only using a standard implementation of CPLEX. Both heuristic approaches can solve significantly larger problems, involving 100-year or even longer planning horizons. Furthermore there are no substantial differences in the solutions produced by the three approaches. It is concluded that for practical purposes a heuristic method is to be preferred to the exact MIP approach. PMID- 26543765 TI - A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22. AB - This phase I/II neoadjuvant trial (ClinicalTrials.gov identifier NCT00066443) determined maximally-tolerated doses (MTD), dose-limiting toxicities, response-to therapy, and explored the role of novel response biomarkers. MA.22 accrued T3N0, any N2 or N3, and T4 breast cancer patients. Treatment was 6 cycles of 3-weekly (Schedule A; N = 47) or 8 cycles of 2-weekly (Schedule B; N = 46) epirubicin/docetaxel chemotherapy in sequential phase I/II studies, with growth factor support. In phase I of each schedule, MTDs were based on DLT. In phase II, clinical responses (CR/PR) and pathologic complete responses (pCR) were assessed. Tumor biopsy cores were obtained pre-, mid-, and post-treatment: 3 for pathologic assessment; 3 for microarray studies. DLT for Schedule A was febrile neutropenia at 105 mg/m(2) epirubicin and 75 mg/m(2) docetaxel; for schedule B, it was fatigue at 75 mg/m(2) for both agents. Phase II doses were 90 mg/m(2) epirubicin/75 mg/m(2) docetaxel for Schedule A and 60 mg/m(2) (both agents) for Schedule B. Schedule A CR/PR and pCR rates were 90 and 10 %, with large reductions in tumor RNA content and integrity following treatment; Schedule B results were 93 and 0 %, with smaller reductions in RNA quality. Pre-treatment expression of several genes was associated with clinical response, including those within a likely amplicon at 17q12 (ERBB2, TCAP, GSDMB, and PNMT). The combination regimens had acceptable toxicity, good clinical response, induction of changes in tumor RNA content and integrity. Pre-treatment expression of particular genes was associated with clinical responses, including several near 17q12, which with ERBB2, may better identify chemoresponsiveness. PMID- 26543766 TI - A case of co-existing paraganglioma and thymoma. AB - BACKGROUND: Head and neck paragangliomas are rare tumours and can arise as a part of inherited syndromes. Their association with thymic tumour is not well known. CASE DESCRIPTION: This report describes a female patient who presented with right sided neck paragangliomas. The histology of the tumour was consistent with paraganlioma. Few years later her MRI scan of the chest revealed presence of an anterior mediastinal mass that corresponded to the location of the thymus. Review of her previous scans showed that the mass was present all along and had gradually increased in size. Patient developed symptoms including fatigue, dyspnoea, migratory polyarthritis, Raynaud's phenomenon and erythema nodosum. She had sternotomy and excision of mediastinal mass. The histology was consistent with cortical thymoma (WHO type B2) and she had radiotherapy. After treatment her constitutional symptoms improved. Her paraganglioma susceptibility genes are negative. DISCUSSION AND EVALUATION: To our knowledge this is only the second case report in the literature of coexistence of carotid body tumour and thymoma. The first case reported was bilateral carotid body tumour, thyroid gland adenoma and thymoma. This case also highlights the importance of long term surveillance, multidisciplinary management and being aware of associated pathologies in patients with isolated paraganglioma. PMID- 26543767 TI - StatXFinder: a web-based self-directed tool that provides appropriate statistical test selection for biomedical researchers in their scientific studies. AB - The improper use of statistical methods is common in analyzing and interpreting research data in biological and medical sciences. The objective of this study was to develop a decision support tool encompassing the commonly used statistical tests in biomedical research by combining and updating the present decision trees for appropriate statistical test selection. First, the decision trees in textbooks, published articles, and online resources were scrutinized, and a more comprehensive unified one was devised via the integration of 10 distinct decision trees. The questions also in the decision steps were revised by simplifying and enriching of the questions with examples. Then, our decision tree was implemented into the web environment and the tool titled StatXFinder was developed. Finally, usability and satisfaction questionnaires were applied to the users of the tool, and StatXFinder was reorganized in line with the feedback obtained from these questionnaires. StatXFinder provides users with decision support in the selection of 85 distinct parametric and non-parametric statistical tests by directing 44 different yes-no questions. The accuracy rate of the statistical test recommendations obtained by 36 participants, with the cases applied, were 83.3 % for "difficult" tests, and 88.9 % for "easy" tests. The mean system usability score of the tool was found 87.43 +/- 10.01 (minimum: 70-maximum: 100). A statistically significant difference could not be seen between total system usability score and participants' attributes (p value >0.05). The User Satisfaction Questionnaire showed that 97.2 % of the participants appreciated the tool, and almost all of the participants (35 of 36) thought of recommending the tool to the others. In conclusion, StatXFinder, can be utilized as an instructional and guiding tool for biomedical researchers with limited statistics knowledge. StatXFinder is freely available at http://webb.deu.edu.tr/tb/statxfinder. PMID- 26543768 TI - Mixture models for analyzing product reliability data: a case study. AB - In the case of manufactured products, there are situations where some components of a product are produced over a period of time by collecting items from different vendors, using different raw materials, machines, and manpower. The physical characteristics and the reliabilities of such components may be different, but sometimes it is difficult to distinguish them clearly. In such situations, mixtures of distributions are often used in the analysis of reliability data for these components. Here a twofold Weibull-Weibull mixture model is applied to analyze product reliability data that consist of both failure and censored lifetimes. The Expectation-Maximization (EM) algorithm is used to find the maximum likelihood estimates of the model parameters. As a case study, it analyses an Aircraft component (Windshield) failure data and various characteristics of the mixture model, such as the reliability function, B10 life, mean time to failure, etc., are estimated to assess the reliability of the component. Simulation studies are performed to investigate the properties and uses of the proposed method. PMID- 26543769 TI - Promoter methylation of TRIM9 as a marker for detection of circulating tumor DNA in breast cancer patients. AB - The aim of the present study was to investigate the promoter methylation status of TRIM9 in breast cancer and to determine the presence of TRIM9-methylated circulating tumor DNA (ctDNA) in plasma. Bisulfite sequencing with a next generation sequencer showed TRIM9 promoter methylation in 92 % (11/12) of breast cancer cell lines (BCCs) and 68 % (13/19) of breast tumor tissues but not in any normal breast tissues (0/19). Methylation ratio of TRIM9 was significantly lower in basal type (9 %, n = 23) than luminal A (69 %, n = 29, P = 0.0003). Quantitative RT-PCR of BCCs disclosed an inverse correlation between TRIM9 mRNA expression and methylation ratio. TRIM9 methylated ctDNA in plasma was detected in 18 % (10/56) of metastatic breast cancer patients but not in any of 60 healthy controls. These results indicate that TRIM9 promoter hypermethylation, which suppresses TRIM9 mRNA expression, occurs in a significant proportion of breast tumors, and that TRIM9-methylated ctDNA thus may serve as a tumor marker for breast cancer. PMID- 26543770 TI - Opsoclonus-myoclonus syndrome after adenovirus infection. AB - Autoimmune and paraneoplastic movement disorders are rare in childhood. Diagnosis often relies on clinical manifestations and clinicians' recognition. A 22-month old girl at onset of opsoclonus-myoclonus syndrome (OMS) was followed for 8 years. Adenovirus (type C subtype 3) infection coincided with manifestation. Data on treatment, imaging and follow-up are provided. In the spinal fluid, elevated anti-rubella antibodies and oligoclonal bands were detected. An autoimmune process affecting mainly cerebellar neurons was revealed immunohistochemically. Moderately intense long-term immunosuppressive therapy resulted in a favorable clinical outcome. A video demonstrated severe OMS manifestations at onset, followed by nearly complete recovery after treatment. We describe the association of a parainfectious OMS and adenovirus infection; laboratory results indicate a non-specific humoral process affecting mainly cerebellar neurons. Our video documentation will aid to recognize this rare movement disorder and to initiate early treatment. PMID- 26543771 TI - CYP3A5 and ABCB1 genotype influence tacrolimus and sirolimus pharmacokinetics in renal transplant recipients. AB - CYP3A5 and ABCB1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements, but the conclusion in the current reports were inconformity. Sirolimus are also metabolized by CYP3A subfamily and are substrates of the P-gp. The aim was to determine whether these polymorphisms affect tacrolimus (TAC) and sirolimus (SRL) trough concentrations and dose requirements after renal transplantation. 153 renal transplant recipients were enrolled into this study, 112 were treated with TAC-based regimen, Another 43 recipients received SRL-based regimen. The recipients' mean follow-up time was 20 mo (range 15-27 mo). All renal transplant recipients were all in a stable stage. The trough concentration and daily dose of TAC and SRL were gained from each recipient. All recipients were genotyped for CYP3A5 (6986A>G), CYP3A4 intron 6 (CYP3A4*22), CYP3A4*18, ABCB1 exon 26 (3435C>T), exon 12 (1236C>T) and 2677G>T/A SNPs by HRM analysis (high-resolution melting curve analysis). The TAC and SRL concentration/dose ratio (C/D) in recipients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (P < 0.05). However, there was no significant correlation between adjusted TAC and SRL trough concentrations or dose requirements with CYP3A4 and ABCB1 SNPs genetic polymorphisms. In recipients with TAC-based or SRL-based therapy, the CYP3A5 genes (6986A>G) can influence the TAC and SRL pharmacokinetics in renal transplant recipients. PMID- 26543774 TI - A study of heat and mass transfer in a fractional MHD flow over an infinite oscillating plate. AB - Exact expressions of velocity, temperature and mass concentration have been calculated for free convective flow of fractional MHD viscous fluid over an oscillating plate. Expressions of velocity have been obtained both for sine and cosine oscillations of plate. Corresponding fractional differential equations have been solved by using Laplace transform and inverse Laplace transform. The expression of temperature and mass concentration have been presented in the form of Fox-H function and in the form of general Wright function, respectively and velocity is presented in the form of integral solutions using Generalized function. Some limiting cases of fluid and fractional parameters have been discussed to retrieve some solutions present in literature. The influence of thermal radiation, mass diffusion and fractional parameters on fluid flow has been analyzed through graphical illustrations. PMID- 26543773 TI - Characterization of Lactobacillus salivarius alanine racemase: short-chain carboxylate-activation and the role of A131. AB - Many strains of lactic acid bacteria produce high concentrations of d-amino acids. Among them, Lactobacillus salivarius UCC 118 produces d-alanine at a relative concentration much greater than 50 % of the total d, l-alanine (100d/d, l-alanine). We characterized the L. salivarius alanine racemase (ALR) likely responsible for this d-alanine production and found that the enzyme was activated by carboxylates, which is an unique characteristic among ALRs. In addition, alignment of the amino acid sequences of several ALRs revealed that A131 of L. salivarius ALR is likely involved in the activation. To confirm that finding, an L. salivarius ALR variant with an A131K (ALR(A131K)) substitution was prepared, and its properties were compared with those of ALR. The activity of ALR(A131K) was about three times greater than that of ALR. In addition, whereas L. salivarius ALR was strongly activated by low concentrations (e.g., 1 mM) of short chain carboxylates, and was inhibited at higher concentrations (e.g., 10 mM), ALR(A131K) was clearly inhibited at all carboxylate concentrations tested (1-40 mM). Acetate also increased the stability of ALR such that maximum activity was observed at 35 degrees C and pH 8.0 without acetate, but at 50 degrees C in the presence of 1 mM acetate. On the other hand, maximum ALR(A131K) activity was observed at 45 degrees C and around pH 9.0 with or without acetate. It thus appears that A131 mediates the activation and stabilization of L. salivarius ALR by short chain carboxylates. PMID- 26543772 TI - Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness. AB - BACKGROUND: The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone's interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects. FINDINGS: The old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses. CONCLUSION: Thus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role. PMID- 26543775 TI - Acute serum sodium concentration changes in pediatric patients undergoing cardiopulmonary bypass and the association with postoperative outcomes. AB - The objective of this study is to investigate the degree of serum sodium changes and its association with patient outcomes in pediatrics undergoing heart surgery with cardiopulmonary bypass (CPB). We reviewed the medical records of 275 pediatric patients who underwent heart surgery with CPB. Prior to CPB, hyponatremia (<=135 mmol/L) was observed in 21 of 275 patients. After initiation of CPB, serum sodium decreased significantly and severe hyponatermia (<=130 mmol/L) subsequently developed in 32 patients. At the end of CPB, however, hypernatremia (>=145 mmol/L) developed in 86 patients. The degree of acute serum sodium change during CPB was not associated with patient outcomes. However, the patients with preoperative hyponatremia and those with hypernatremia at the conclusion of CPB had longer hospital stays and higher postoperative complication rates. Lower serum sodium prior to CPB and higher serum sodium at the end of CPB, along with age and duration of the operation, were independently associated with worse in-hospital outcomes. Acute and transient hyponatremia occurred frequently after initiation of CPB, and then serum sodium immediately increased above preoperative levels at the end of CPB. Caution is required to avoid serum sodium overcorrection on the conclusion of CPB. PMID- 26543776 TI - Bacteriological safety of packaged drinking water sold in Nigeria: public health implications. AB - BACKGROUND: Over the past years, there has been increase in packaged water consumption in Nigeria. Although, there are several studies on microbial safety of sachet packaged drinking water, there is no information on prevailing pathogens. FINDINGS: A comprehensive literature search and meta-analysis of peer reviewed primary studies reported from 2005 for microbiological safety of packaged drinking water sold in Nigeria was conducted using "sachet water", "bottled water" and "packaged water" and Nigeria as search algorithms in public scientific literature databases. It was observed in this study that Escherichia spp., (65.5 %), Salmonella spp., (44.8 %), Bacillus spp., (44.1 %) and Staphylococcus spp. (37.9 %) were more prevailing in the samples. CONCLUSIONS: The high rate of contamination observed is of public health importance. There is need for use of molecular based methods to understand microbial ecology, epidemiology, virulence factors and survival of isolated water borne pathogens in packaged drinking water sold in Nigeria. PMID- 26543777 TI - Li4Ti5O12/graphene nanoribbons composite as anodes for lithium ion batteries. AB - In this paper, we report the synthesis of a Li4Ti5O12/Graphene Nanoribbons (LTO/GNRs) composite using a solid-coating method. Electron microscope images of the LTO/GNRs composite have shown that LTO particles were wrapped around graphene nanoribbons. The introduction of GNRs was observed to have significantly improved the rate performance of LTO/GNTs. The specific capacities determined of the obtained composite at rates of 0.2, 0.5, 1, 2, and 5 C are 206.5, 200.9, 188, 178.1 and 142.3 mAh.g(-1), respectively. This is significantly higher than those of pure LTO (169.1, 160, 150, 106 and 71.1 mAh.g(-1), respectively) especially at high rate (2 and 5 C). The LTO/GNRs also shows better cycling stability at high rates. Enhanced conductivity of LTO/GNRs contributed from the GNR frameworks accelerated the kinetics of lithium intercalation/deintercalation in LIBs that also leads to excellent rate capacity of LTO/GNRs. This is attributed to its lower charge-transfer resistance (Rct = 23.38 Omega) compared with LTO (108.05 Omega), and higher exchange current density (j = 1.1 * 10(-3) mA cm(-2))-about 20 times than those of the LTO (j = 2.38 * 10(-4) mA cm(-2)). PMID- 26543778 TI - A preliminary study on improving the recognition of esophageal speech using a hybrid system based on statistical voice conversion. AB - In this paper, we propose a hybrid system based on a modified statistical GMM voice conversion algorithm for improving the recognition of esophageal speech. This hybrid system aims to compensate for the distorted information present in the esophageal acoustic features by using a voice conversion method. The esophageal speech is converted into a "target" laryngeal speech using an iterative statistical estimation of a transformation function. We did not apply a speech synthesizer for reconstructing the converted speech signal, given that the converted Mel cepstral vectors are used directly as input of our speech recognition system. Furthermore the feature vectors are linearly transformed by the HLDA (heteroscedastic linear discriminant analysis) method to reduce their size in a smaller space having good discriminative properties. The experimental results demonstrate that our proposed system provides an improvement of the phone recognition accuracy with an absolute increase of 3.40 % when compared with the phone recognition accuracy obtained with neither HLDA nor voice conversion. PMID- 26543779 TI - Facial expression recognition and histograms of oriented gradients: a comprehensive study. AB - Automatic facial expression recognition (FER) is a topic of growing interest mainly due to the rapid spread of assistive technology applications, as human robot interaction, where a robust emotional awareness is a key point to best accomplish the assistive task. This paper proposes a comprehensive study on the application of histogram of oriented gradients (HOG) descriptor in the FER problem, highlighting as this powerful technique could be effectively exploited for this purpose. In particular, this paper highlights that a proper set of the HOG parameters can make this descriptor one of the most suitable to characterize facial expression peculiarities. A large experimental session, that can be divided into three different phases, was carried out exploiting a consolidated algorithmic pipeline. The first experimental phase was aimed at proving the suitability of the HOG descriptor to characterize facial expression traits and, to do this, a successful comparison with most commonly used FER frameworks was carried out. In the second experimental phase, different publicly available facial datasets were used to test the system on images acquired in different conditions (e.g. image resolution, lighting conditions, etc.). As a final phase, a test on continuous data streams was carried out on-line in order to validate the system in real-world operating conditions that simulated a real-time human machine interaction. PMID- 26543781 TI - The q-G method : A q-version of the Steepest Descent method for global optimization. AB - In this work, the q-Gradient (q-G) method, a q-version of the Steepest Descent method, is presented. The main idea behind the q-G method is the use of the negative of the q-gradient vector of the objective function as the search direction. The q-gradient vector, or simply the q-gradient, is a generalization of the classical gradient vector based on the concept of Jackson's derivative from the q-calculus. Its use provides the algorithm an effective mechanism for escaping from local minima. The q-G method reduces to the Steepest Descent method when the parameter q tends to 1. The algorithm has three free parameters and it is implemented so that the search process gradually shifts from global exploration in the beginning to local exploitation in the end. We evaluated the q G method on 34 test functions, and compared its performance with 34 optimization algorithms, including derivative-free algorithms and the Steepest Descent method. Our results show that the q-G method is competitive and has a great potential for solving multimodal optimization problems. PMID- 26543780 TI - Spatial and temporal variations in environmental variables in relation to phytoplankton composition and biomass in coral reef areas around Unguja, Zanzibar, Tanzania. AB - Phytoplankton can indirectly indicate health status of coral reefs due to their sensitivity to changes in water quality parameters. This study explored the spatial and temporal variability in water quality and nutrients in relation to phytoplankton community composition and chlorophyll a concentration at Bawe, Mnemba, Chumbe and Pongwe coral reef sites in Unguja Island. In situ measurements of dissolved oxygen, temperature, salinity and pH were done every month for 1 year. Surface water samples were collected for determination of phytoplankton composition, nutrients and chlorophyll a concentration. Dissolved oxygen, temperature, salinity and pH did not differ significantly among the four sites (p > 0.05) but showed significant temporal variations among months (p < 0.05). Bawe had significantly higher phosphate concentration (1.45 +/- 0.57 ug L(-1)) than Chumbe (0.74 +/- 0.53 ug L(-1)), Mnemba (0.42 +/- 0.30 ug L(-1)) and Pongwe (0.28 +/- 0.10 ug L(-1); p < 0.05). Similarly, Bawe had significantly higher nitrate concentration (0.81 +/- 0.43 ug L(-1)) than Mnemba (0.33 +/- 0.14 ug L(-1)) and Pongwe (0.24 +/- 0.13 ug L(-1); p < 0.05) but similar to Chumbe (0.90 +/- 0.35 ug L(-1); p > 0.05). However, values obtained at all the studied sites were less than 3 and 14 mg L(-1) for phosphate and nitrate, respectively, for eutrophic oceans. Phytoplankton species were dominated by Bacillariophyceae (70.83 %) and some species identified such as Ceratium sp., Dinophysis sp., Protoperidinium sp., Prorocentrum sp., Oscillatoria sp. and Dictyocha fibula are known to produce toxins that affect fish species. Bawe had significantly higher chlorophyll a concentration (0.47 +/- 0.07 mg L(-1)) than Mnemba (0.33 +/- 0.04 mg L(-1)) and Chumbe (0.33 +/- 0.04 mg L(-1); p < 0.05). Chlorophyll a concentration was spatially inversely related to distance from Unguja town (p < 0.05) while it was temporally significantly positively correlated with dissolved oxygen, nitrate and phosphate (p < 0.05). The study revealed that, the coral reef sites have low nutrient levels and are in good health. The existence of toxic phytoplankton species suggests careful consumption of fisheries resources at the four coral reef sites and frequent monitoring for Harmful Algal Blooms (HABs) is required. The higher nutrients and chlorophyll a concentrations at Bawe Island compared to other sites calls for mechanisms to limit the release of domestic sewage from households and hotels to safeguard the coral reefs. PMID- 26543782 TI - Solution of nonlinear higher-index Hessenberg DAEs by Adomian polynomials and differential transform method. AB - The solution of higher-index Hessenberg differential-algebraic equations (DAEs) is of great importance since this type of DAEs often arises in applications. Higher-index DAEs are known to be numerically and analytically difficult to solve. In this paper, we present a new analytical method for the solution of two classes of higher-index Hessenberg DAEs. The method is based on Adomian polynomials and the differential transform method (DTM). First, the DTM is applied to the DAE where the differential transforms of nonlinear terms are calculated using Adomian polynomials. Then, based on the index condition, the resulting recursion system is transformed into a nonsingular linear algebraic system. This system is then solved to obtain the coefficients of the power series solution. The main advantage of the proposed technique is that it does not require an index reduction nor a linearization. Two test problems are solved to demonstrate the effectiveness of the method. In addition, to extend the domain of convergence of the approximate series solution, we propose a post-treatment with Laplace-Pade resummation method. PMID- 26543783 TI - Levels of nicotine in Ethiopian tobacco leaves. AB - Tobacco is a valuable cash crop. It is the most widely grown non-food crop in the world. Tobacco use is widespread due to its addictive nature of its main constituent nicotine. Therefore, the knowledge of nicotine level in tobacco is important to tobacco industry and in the area of toxicology to control its harmful effect on health. There is no report in the literature on nicotine level of Ethiopian raw (unprocessed) tobacco leaves. Hence, the objective of this study is to determine the levels of nicotine in the Ethiopian tobacco leaves. Samples were collected based on their leaves positions, species and place of cultivation from different regions of Ethiopia. These were Virginia type tobacco from Shewa Robit and Billate, Burley and Oriental types of tobacco from Awassa and native tobacco used as pipe smoking (Gaya) from Wollayita. The level of nicotine in four different varieties of Ethiopian tobacco leaves was determined using high performance liquid chromatography. The level of nicotine in the four different varieties of Ethiopian tobacco were Virginia tobacco (3.26 %), the native tobacco 'Gaya' (1.10 %), Burley tobacco (0.650 %), and Oriental tobacco leaves (<=0.0500 %). It was found that the nicotine level of Ethiopian Virginia tobacco leaves increases from bottom to top leaf (stalk) positions of the tobacco plant. It was also found that the nicotine level of Ethiopian tobacco leaves varies in different species and the nicotine level of the same tobacco species differ in different area of cultivation. In general, the level of nicotine in Ethiopian tobacco is comparable with that in the rest of the world. PMID- 26543785 TI - Comparison of five different popular scoring systems to predict nonsentinel lymph node status in patients with metastatic sentinel lymph nodes: a tertiary care center experience. AB - Sentinel lymph node biopsy (SLNB) is the current standard of care for breast cancers with no clinically palpable axillary lymph nodes. Almost 50 % of sentinel lymph node positive patients have negative non-sentinel nodes and undergo non therapeutic axillary dissection. Five different scoring systems, reported in the literature, were compared for their predictive ability of non-SLN involvement in patients with SLN positive breast cancer. 242 patients who underwent breast surgery and SLNB were included in the study. Of these, 70 who were confirmed to have SLN metastasis and received complementary ALND and constituted the final study population. The nomograms (MSKCC, M.D. Anderson Cancer Center, Tenon model, Stanford and Turkish) were statistically compared for their prediction of non-SLN metastasis (95 % confidence interval). We have determined only two clinicopathologic (multifocality and size of the primary tumor) situations which have a statistically significant association between SLN metastasis with using a multivariate logistic regression analysis. Multifocality (P = 0.001) and size of the primary tumor (P = 0.001) were associated with a higher probability of-SLN metastasis. No predictive model was constructed that showed good area under the curve (AUC) discrimination in the validation series. Currently published predictive models lack accuracy when applied to a different population. Multi institutional heterogenic population studies are important to determine the exact combination of scoring systems and/or nomograms. PMID- 26543786 TI - Development and validation of a LC-MS/MS method for quantification of hetrombopag for pharmacokinetics study. AB - Hetrombopag as the derivative of ethylidene hydrazine carboxamide was recently developed into a novel patented non-peptide thrombopoietin mimetic and thrombopoietin receptor agonist to treat idiopathic thrombocytopenic purpura. To study the pharmacokinetics of hetrombopag, a highly sensitive, rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of hetrombopag in rat plasma. After protein precipitation extraction, the chromatography separation of analyte and internal standard named eltrombopag as an marketed analog of hetrombopag was performed on an Synergi Polar-RP column at the flow rate of 0.5 mL/min, and the determination was conducted on an API4000 triple quadrupole mass spectrometry in the multiple reaction monitoring mode using the respective [M+H](+) ions m/z 459.2 -> 200.9 for hetrombopag and m/z 443.2 -> 229.0 for IS. The lower limit of quantification was established to be 1 ng/mL, and the linear scope of standard curve was 1-1000 ng/mL. Both the precision (RSD%) and accuracy (RE%) were within the acceptable criterion of below 15 %. The validated method was successfully applied to quantify hetrombopag in the rat plasma and investigate the pharmacokinetics. PMID- 26543784 TI - Pacing in a self-paced world record attempt in 24-h road cycling. AB - BACKGROUND: Pacing strategy plays a major role in sport performance. However, there is a dearth of knowledge concerning pacing during ultra-endurance sport events. The present case study investigated the pacing of an ultra-cyclist in a self-paced attempt to break the world record in 24-h road cycling and, with all the caveats and the limitations affecting a case report, could be useful in generating hypotheses and further studies about pacing dynamics during prolonged sport performances. CASE DESCRIPTION: A well experienced ultra-cyclist completed laps of 11.731 km during 24 h and the support crew recorded for each lap time and power output in Watt. The trend in cycling speed and power output across laps was investigated using regression analyses. A mixed-effects regression model including lap, ambient air temperature, air pressure, air humidity and wind speed as fixed variables was used to investigate a relationship of environmental factors with cycling speed. DISCUSSION AND EVALUATION: The athlete achieved 896.173 km within the 24 h. He set a new world record by breaking the old record (Jure Robic, 2004, 834.77 km) by 61.403 km. He cycled at an average speed of 37.34 km/h with an average power output of 250.2 W. The decrease in cycling speed and power output across laps could be modelled linearly. Temperature and wind speed were related to cycling speed during the whole event. There was a significant interaction air temperature * relative humidity for the whole event. CONCLUSIONS: The athlete adopted a positive pacing (i.e. speed gradually declined throughout the event) and environmental factors (i.e. temperature and wind speed) influenced cycling speed during the event. PMID- 26543787 TI - Emergency management training in Korea: combining and balancing supply- and demand-centered paradigms. AB - This article aims to encourage NEMA (or newly named as MPSS) to combine its supply-centered paradigm with a newly proposed "demand-centered paradigm" in the Korean field of emergency management training (EMT). Based on qualitative content analysis, this paper defined the current field of EMT to be a supply-centered paradigm via three components: locations, courses, and participants. This paradigm focuses on EMT provision as supplied and dictated by the national government. On the other hand, a demand-centered model is about looking into stakeholders' actual needs for EMT. In this regard, alternatives with reference to the demand-centered paradigm via the same three components were discussed and considered. The key tenet is that having revealed that NEMA has unequivocally focused on the results side or effectiveness of EMT via a supply-centered paradigm, Korea should address and consider the same three components, this time by fusing and incorporating a fair process of EMT by enlisting active roles from the local community, academic scholars, and civilian training attendees in a demand-centered paradigm. PMID- 26543788 TI - Functional characterization of a yellow laccase from Leucoagaricus gongylophorus. AB - In this work we have identified, using mass spectrometry, two laccases produced by Leucoagaricus gongylophorus. One of them, Lac1Lg, was isolated, purified and characterized. Lac1Lg, a monomeric enzyme, was studied using ABTS and syringaldazine substrates. Lac1Lg presented kcat/Km almost threefold higher for syringaldazine than for ABTS, showing a higher catalytic efficiency of Lac1Lg for syringaldazine. The interference of several metal ions and substances in the laccase activity were evaluated. Lac1Lg did not absorb at 600 nm, which is a characteristic of so-called yellow laccases. Lac1Lg also was able to oxidize non phenolic substrate (anthracene) in the absence of an exogenous mediator, showing that the enzyme has potential to explore in biotechnological processes. Our Lac1Lg three-dimensional molecular model, constructed using homology modeling, showed that the Lac1Lg catalytic site is very closed to blue laccases. PMID- 26543790 TI - Contaminant release history identification in 2-D heterogeneous aquifers through a minimum relative entropy approach. AB - The minimum relative entropy (MRE) method has been applied in a wide variety of fields since it was first introduced. Woodbury and Ulrych (Water Resour Res 29(8): 2847-2860, 1993, Water Resour Res 32(9): 2671-2681, 1996) adopted and improved this method to solve linear inverse problems in aquifers. In this work, the MRE method was improved to detect the source release history in 2-D aquifer characterized by a non-uniform flow-field. The approach was tested on two cases: a 2-D homogeneous conductivity field and a heterogeneous one (the hydraulic conductivity presents three orders of magnitude in terms of variability). In the latter case the transfer function cannot be described with an analytical formulation, thus, the transfer functions were estimated by means of a numerical procedure. In order to analyze the method performance in different conditions, two datasets have been used: observations collected at the same time at 20 different monitoring points, and observations collected at 2 monitoring points at several times. The observed data have been processed with and without a random error and the Boxcar and Gaussian probability distribution functions were considered as a priori information. The agreement between the true and the estimated data has been evaluated through the calculation of the normalized Root Mean Square error. The approach was able to recover the release history even in the most difficult case. PMID- 26543789 TI - Exercise-based interventions for cancer survivors in India: a systematic review. AB - Existing literature suggests that cancer survivors present with high rates of morbidity due to various treatment and disease induced factors. Research globally has shown exercise to be beneficial in improving treatment outcomes and quality of life. India has a high prevalence of cancer and not much is known about exercise interventions for cancer survivors in India. This review was planned to review the state of exercise based interventions for cancer survivors in India. A comprehensive literature search was performed in PubMed, CINAHL, EMBASE, Scopus, Cochrane Library, PEDro, IndMed, and Shoda Ganga. The search results were screened and data extracted by two independent reviewers. All eligible studies were assessed for methodological quality rating using Downs and Black checklist. Data was extracted using a pilot tested pro forma to summarize information on site and stage of cancer, type of exercise intervention and outcome measures. The review identified 13 studies, published from 1991 to 2013, after screening 4060 articles. Exercise interventions fell into one of three categories: (1) yoga based, (2) physiotherapy-based and (3) speech therapy based interventions; and exclusively involved either breast or head and neck cancers. Studies were generally of low to moderate quality. A broad range of outcomes were found including symptoms, speech and swallowing, and quality of life and largely supported the benefits of exercise-based interventions. At present, research involving exercise-based rehabilitation interventions in India is limited in volume, quality and scope. With the growing burden of cancer in the country, there is an immediate need for research on exercise based interventions for cancer survivors within the sociocultural context of India. PMID- 26543791 TI - Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis. AB - The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 +/- 139 ng/mL for the stable phase of IPF, 645 +/- 247 ng/mL for early phase of acute exacerbation of IPF, 534 +/- 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 +/ 42 for chronic obstructive pulmonary disease, and 150 +/- 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM 1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers. PMID- 26543792 TI - Hydrolyzed fish proteins reduced activation of caspase-3 in H2O2 induced oxidative stressed liver cells isolated from Atlantic salmon (Salmo salar). AB - Hydrolyzed fish proteins (H-pro) contains high concentrations of free amino acids and low molecular peptides that potentially benefit health. The following study aimed to test whether the water soluble phase of H-pro could reduce apoptosis and inflammation in primary liver cells isolated from Atlantic salmon following H2O2 provoked oxidative stress. Cells were grown as monocultures or co-cultured with head kidney cells to assess possible cross talk in inflammation and metabolism during treatments. Cells were grown in media with or without H-pro for 2 days before being stressed with 200 uM H2O2 then harvested 24 h post exposure. Both treatments were compared to the respective treatments without H2O2 supplementation. Oxidative stressed cells had increased activation of caspase-3, but supplementation with H-pro in the media prior to the oxidative stress reduced caspase-3 activation. In conclusion, free amino acids and low molecular weight peptides from H-pro attenuated oxidative stress, and made cells able to withstand apoptosis after H2O2 provoked oxidative stress. PMID- 26543793 TI - Stress analysis of parallel oil and gas steel pipelines in inclined tunnels. AB - Geological conditions along long distance pipelines are complex. In consideration of differences in elevation and terrain obstacles, long distance pipelines are commonly laid through tunnels. Oil and gas pipelines are often laid side by side to reduce construction costs and minimize geological impact. The layout and construction of parallel oil and gas pipelines are more complex than those of single pipelines. In order to reduce safety hazards, it is necessary to carry out stress analysis of the oil and gas pipelines that run through tunnels. In this study, a stress analysis model of pipelines running through a tunnel was developed. On the basis of the finite element method, CAESAR II software was used to analyze the stress and displacement of a section of parallel oil and gas pipelines that run through tunnels and stress and displacement distribution laws were drawn from the analyses. A study of the factors influencing stress recommended that: (1) The buttress interval of the parallel oil and gas pipelines in a tunnel should be 12 m; (2) The angle of inclined pipelines should be no greater than 25 degrees ; (3) The stress of oil pipelines enhances more obviously than that of gas pipelines under earthquake action; (4) The average stress can be reduced by adopting "ladder" laying; and (5) Guide bend can be set at the tunnel entrance and exit in order to reduce the stress. PMID- 26543794 TI - What Happens When Children with Fetal Alcohol Spectrum Disorders Become Adults? AB - The range of structural abnormalities and functional deficits caused by prenatal alcohol exposure (PAE) are referred to as fetal alcohol spectrum disorders (FASDs). The disabilities associated with FASDs are said to be lifelong, but we know relatively little regarding outcomes beyond childhood and adolescence. Many of physical, brain, and neurobehavioral features that are present in children with FASDs will endure to adulthood. However, some features may diminish or change over time. Furthermore, secondary disabilities, such as school drop outs, trouble with the law, and substance/alcohol abuse problems are common in young adults with FASDs. The health consequences associated with PAE in the human adult are unknown, but animal models suggest that they may be more susceptible to chronic diseases such as hypertension, diabetes, immune dysfunction, and cancer. More research is needed to understand the lasting effects of PAE on adults and the developmental trajectories of FASDs. PMID- 26543795 TI - Executive Function in SLI: Recent Advances and Future Directions. AB - This paper provides a review of recent research on executive function abilities in children with specific language impairment (SLI). Across several studies, children with SLI are reported to perform worse than typically developing peers on measures of sustained attention, working memory, inhibition, and attention shifting. However, few studies have considered multiple executive function components simultaneously and even fewer have examined the underlying relationship between executive function deficits and impaired language acquisition. We argue that in order to fully understand the nature of executive function deficits in SLI, the field must move past simply identifying weaknesses to instead test models of executive function development and explore the nature of the relationship between executive function and language. Future research directions are recommended in order to achieve these goals. PMID- 26543796 TI - Neuroimaging in Tourette Syndrome: Research Highlights From 2014-2015. AB - Tourette Syndrome (ts) is a developmental neuropsychiatric disorder of the central nervous system defined by the presence of chronic tics. While investigations of the underlying brain mechanisms have provided valuable information, a complete understanding of the pathophysiology of ts remains elusive. Neuroimaging methods provide remarkable tools for examining the human brain, and have been used to study brain structure and function in ts. In this article, we review ts neuroimaging studies published in 2014-2015. We highlight a number of noteworthy studies due to their innovative methods and interesting findings. Yet, we note that many of the recent studies share common concerns, specifically susceptibility to motion artifacts and modest sample sizes. Thus, we encourage future work to carefully address potential methodological confounds and to study larger samples to increase the potential for replicable results. PMID- 26543797 TI - Behavior Therapy for Tic Disorders: An Evidenced-based Review and New Directions for Treatment Research. AB - Behavior therapy is an evidenced-based intervention with moderate-to-large treatment effects in reducing tic symptom severity among individuals with Persistent Tic Disorders (PTDs) and Tourette's Disorder (TD). This review describes the behavioral treatment model for tics, delineates components of evidence-based behavior therapy for tics, and reviews the empirical support among randomized controlled trials for individuals with PTDs or TD. Additionally, this review discusses several challenges confronting the behavioral management of tics, highlights emerging solutions for these challenges, and outlines new directions for treatment research. PMID- 26543798 TI - Dyslexia-Early Identification and Prevention: Highlights from the Jyvaskyla Longitudinal Study of Dyslexia. AB - Over two decades of Finnish research, monitoring children born with risk for dyslexia has been carried out in the Jyvaskyla Longitudinal Study of Dyslexia (JLD). Two hundred children, half at risk, have been assessed from birth to puberty on hundreds of measures. The aims were to identify measures of prediction of later reading difficulty and to instigate appropriate and earliest diagnosis and intervention. We can identify at-risk children from newborn electroencephalographic brain recordings (Guttorm et al., J Neural Transm 110:1059-1074, 2003). Predictors are also apparent from late-talking infants who have familial background of dyslexia (Lyytinen and Lyytinen, Appl Psycolinguistics 25:397-411, 2004). The earliest easy-to-use predictive measure to identify children who need help to avoid difficulties in learning to read is letter knowledge (Lyytinen et al., Merrill-Palmer Q 52:514-546, 2006). In response, a purpose-engineered computer game, GraphoGameTM, provides an effective intervention tool (Lyytinen et al., Scand J Psychol 50:668-675, 2009). In doubling as a research instrument, GraphoGame provides bespoke intervention/reading instruction for typical/atypically developing children. Used extensively throughout Finland, GraphoGame is now crossing the developed and developing world to assist children, irrespective of the cause (environmental or genetic) of their failing to learn to read (Ojanen et al., Front Psychol 6(671):1 13, 2015). PMID- 26543799 TI - Behavioral and Neuroimaging Research of Reading: a Case of Japanese. AB - Behavioral studies showed that AS, an English-Japanese bilingual, was a skilled reader in Japanese but was a phonological dyslexic in English. This behavioral dissociation was accounted for by the Hypothesis of Transparency and Granularity postulated by Wydell and Butterworth. However, a neuroimaging study using magnetoencephalography (MEG) revealed that AS has the same functional deficit in the left superior temporal gyrus (STG). This paper therefore offers an answer to this intriguing discrepancy between the behavioral dissociation and the neural unity in AS by reviewing existing behavioral and neuroimaging studies in alphabetic languages such as English, Finnish, French, and Italian, and nonalphabetic languages such as Japanese and Chinese. PMID- 26543800 TI - Update on Disease-Modifying/Preventive Therapies in Alzheimer's Disease. AB - Alzheimer's disease (AD) is increasingly becoming a major health problem throughout the US and Western Europe. As the remnants of the Baby Boom generation begin to reach their seniority at the turn of the twenty-first century, the disease has been unwillingly brought to the attention of the public eye. A disease that has traditionally been associated with an aging population has thus become a heated topic of discussion as modern research attempts to prevent and treat this major health burden and plague of the next decade. PMID- 26543801 TI - The Crossroads of Geriatric Cardiology and Cardio-Oncology. AB - Cancer and cardiovascular disease (CVD) are two major causes of mortality in older adults. With improved survival and outcomes from cancer and CVD, the role of the geriatrician is evolving. Geriatricians provide key skills to facilitate patient-centered and value-based care in the growing older population of cancer patients (and survivors). Cancer treatment in older adults is particularly injurious with respect to complications stemming from cancer therapy and as well as to CVD related to cancer therapy in the context of physiologic aging. To best meet their natural potential as caregiving leaders, geriatricians must hone skills and insights pertaining to oncologic and cardiovascular care, insights that can inform and enhance key management expertise. In this paper, we will review common chemotherapy and radiation-induced cardiovascular complications, screening recommendations, and advance the concept of a geriatric, cardiology, and oncology collaboration. We assert that geriatricians are well suited to a leadership role in the care of older cardio-oncology patients and in the education of primary care physicians and subspecialists on geriatric principles. PMID- 26543802 TI - Cost-Effectiveness of Radiofrequency Ablation for Supraventricular Tachycardia in Guatemala: Patient outcomes and economic analysis from a low-middle-income country. AB - BACKGROUND: Radiofrequency ablation (RFA) is an established but expensive treatment alternative for many forms supraventricular tachycardia (SVT). Currently no studies exist on the cost-effectiveness of RFA compared to medical treatment (MT) in adult Latin American population. METHODS: Between 2007 and 2012, we identified 103 adults who underwent RFA for SVT in the National Unit of Cardiovascular Surgery (UNICAR) in Guatemala. A decision tree was developed with all clinical outcome parameter estimates obtained from the Adult Electrophysiology Clinic. Costs were obtained from UNICAR's administration. A cost-effectiveness analysis was conducted which evaluated costs and quality adjusted life years (QALYs) to compare interventions in terms of their incremental cost-effectiveness ratios (ICERs). RESULTS: The first RFA had 83% success and cumulative 94% success was achieved with a second one. The cost of the RFA procedure itself was $5,411. RFA gains 1.46 QALYs and saves $ 7,993 compared to of MT for patients with SVT. This demonstrates that in Guatemala, RFA dominates MT in the management of SVT. Using assumptions based largely on the outcomes in UNICAR, we found that the RFA is highly cost-effective. This is a consistent finding, even after varying assumptions about efficacy, complication rates and quality of life. CONCLUSIONS: RFA dominates MT by improving quality of life and reducing expenditures when used to treat severely symptomatic patients with SVT in Guatemala. The robustness of these finding to variations in parameter assumptions, suggests these findings may hold in other similar settings. PMID- 26543803 TI - Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease. AB - Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re emerging human pathogens, in wildlife reservoirs. PMID- 26543804 TI - The African buffalo parasite Theileria. sp. (buffalo) can infect and immortalize cattle leukocytes and encodes divergent orthologues of Theileria parva antigen genes. AB - African Cape buffalo (Syncerus caffer) is the wildlife reservoir of multiple species within the apicomplexan protozoan genus Theileria, including Theileria parva which causes East coast fever in cattle. A parasite, which has not yet been formally named, known as Theileria sp. (buffalo) has been recognized as a potentially distinct species based on rDNA sequence, since 1993. We demonstrate using reverse line blot (RLB) and sequencing of 18S rDNA genes, that in an area where buffalo and cattle co-graze and there is a heavy tick challenge, T. sp. (buffalo) can frequently be isolated in culture from cattle leukocytes. We also show that T. sp. (buffalo), which is genetically very closely related to T. parva, according to 18s rDNA sequence, has a conserved orthologue of the polymorphic immunodominant molecule (PIM) that forms the basis of the diagnostic ELISA used for T. parva serological detection. Closely related orthologues of several CD8 T cell target antigen genes are also shared with T. parva. By contrast, orthologues of the T. parva p104 and the p67 sporozoite surface antigens could not be amplified by PCR from T. sp. (buffalo), using conserved primers designed from the corresponding T. parva sequences. Collectively the data re-emphasise doubts regarding the value of rDNA sequence data alone for defining apicomplexan species in the absence of additional data. 'Deep 454 pyrosequencing' of DNA from two Theileria sporozoite stabilates prepared from Rhipicephalus appendiculatus ticks fed on buffalo failed to detect T. sp. (buffalo). This strongly suggests that R. appendiculatus may not be a vector for T. sp. (buffalo). Collectively, the data provides further evidence that T. sp. (buffalo). is a distinct species from T. parva. PMID- 26543805 TI - Cryptosporidium rubeyi n. sp. (Apicomplexa: Cryptosporidiidae) in multiple Spermophilus ground squirrel species. AB - Previously we reported the unique Cryptosporidium sp. "c" genotype (e.g., Sbey03c, Sbey05c, Sbld05c, Sltl05c) from three species of Spermophilus ground squirrel (Spermophilus beecheyi, Spermophilus beldingi, Spermophilus lateralis) located throughout California, USA. This follow-up work characterizes the morphology and animal infectivity of this novel genotype as the final step in proposing it as a new species of Cryptosporidium. Analysis of sequences of 18S rRNA, actin, and HSP70 genes of additional Cryptosporidium isolates from recently sampled California ground squirrels (S. beecheyi) confirms the presence of the unique Sbey-c genotype in S. beecheyi. Phylogenetic and BLAST analysis indicates that the c-genotype in Spermophilus ground squirrels is distinct from Cryptosporidium species/genotypes from other host species currently available in GenBank. We propose to name this c-genotype found in Spermophilus ground squirrels as Cryptosporidium rubeyi n. sp. The mean size of C. rubeyi n. sp. oocysts is 4.67 (4.4-5.0) MUm * 4.34 (4.0-5.0) MUm, with a length/width index of 1.08 (n = 220). Oocysts of C. rubeyi n. sp. are not infectious to neonatal BALB/c mice and Holstein calves. GenBank accession numbers for C. rubeyi n. sp. are DQ295012, AY462233, and KM010224 for the 18S rRNA gene, KM010227 for the actin gene, and KM010229 for the HSP70 gene. PMID- 26543806 TI - Caryospora neofalconis and other enteroparasites in raptors from Mexico. AB - A coprological survey of enteroparasites in raptors (60 Falconiformes) from Central Mexico is reported. Three samples contained coccidian unsporulated oocysts, one contained Eimeria sp., one contained trematode eggs and one contained capillarid and trematode eggs and Eimeria sp. After sporulation at the laboratory, oocysts from a Falco peregrinus were identified as Caryospora neofalconis. The phylogenetic analysis of the C. neofalconis (GenBank accession number KT037081) showed a close relationship to the Australian strain RY 2014 isolate 16710 (GenBank accession number KJ634019) of Caryospora daceloe, with 99.2% similarity. As far as we are aware, this is the first report of C. neofalconis in raptors from Mexico and the Americas. PMID- 26543807 TI - Use of the mTOR inhibitor everolimus in a patient with multiple manifestations of tuberous sclerosis complex including epilepsy. AB - Tuberous sclerosis complex (TSC) is a genetic disease in which overactivation of mechanistic target of rapamycin (mTOR) signaling leads to the growth of benign hamartomas in multiple organs, including the brain, and is associated with a high rate of epilepsy and neurological deficits. The mTOR inhibitor everolimus has been used in the treatment of subependymal giant cell astrocytomas and renal angiomyolipomas in patients with TSC. This article describes the case of a 13 year-old girl with TSC-associated epilepsy with refractory generalized seizures who initiated treatment with everolimus and experienced subsequent improvement in several TSC manifestations, including a reduction in seizure frequency from clusters of two or three daily to one every 2 to 4 weeks after 1.5 years of treatment. PMID- 26543808 TI - Anticonvulsant-induced downbeat nystagmus in epilepsy. AB - We report data from two patients who developed reversible downbeat nystagmus (DBN) while using AEDs within the therapeutic range. All previous reported cases of epilepsy with drug-induced DBN related to toxic levels of AEDs were summarized, and DBN was found mostly occurring in those using a sodium channel blocking AED. We propose that in our cases, the DBN with therapeutic AED levels may be explained by additive effects of sodium channel blockers. Adverse drug effects should be considered as a cause of DBN in people with epilepsy treated with multiple AEDs. PMID- 26543809 TI - Reactivation of herpes simplex virus-1 following epilepsy surgery. AB - PURPOSE: The present study reports a case of encephalitis due to herpes simplex virus-1 (HSV-1), following surgical manipulation of the site of a primary infection. METHODS: Herpes simplex virus-1 infection was confirmed by CSF PCR and DNA sequencing. RESULTS: The patient was an 11-year-old girl who required temporal lobe surgery for epilepsy. She had meningoencephalitis due to HSV at the age of 20 months, and she was treated with acyclovir. Three years later, the patient developed uncontrolled seizures that became more frequent and changed in character at 11 years of age. On the 12th postoperative day, she developed fever and seizures, and she was diagnosed with HSV-1 by positive CSF PCR. She was treated with acyclovir (30 mg/kg/day for 21 days). In this report, we describe the patient and review the relevant literature. CONCLUSION: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever. PMID- 26543810 TI - Levetiracetam-induced rage and suicidality: Two case reports and review of literature. AB - BACKGROUND: Levetiracetam-induced rage is a rare neurobehavioral adverse effect of levetiracetam that is characterized by seething rage, uncontrollable anger, fits of fury, depression, violence, and suicidal tendencies. It occurs more in patients with prior mood or psychotic disturbances. No such case has been reported in Nigeria. METHOD: We report two cases of levetiracetam-induced rage. The first patient was a 29-year-old male with a 14-year history of intractable posttraumatic epilepsy. He was initially placed on sodium valproate and phenobarbitone and later had phenobarbitone replaced with levetiracetam. Within the first week of initiating levetiracetam, he became aggressive, bursted into fits of fury, and attacked his siblings. Levetiracetam was stopped, and the seething rage ceased only to reappear when it was reintroduced; hence, the complete withdrawal of levetiracetam. Naranjo probability score for adverse drug reaction was 8. RESULTS: The second patient was a 23-year-old lady who developed seething rage and made several attempts to kill herself with a knife following addition of levetiracetam to the clonazepam and carbamazepine that she was taking for treatment-resistant epilepsy. Withdrawal and reintroduction of levetiracetam by the relatives led to cessation and reemergence, respectively, of the rage and suicidal tendencies. Naranjo score was 8. Levetiracetam was discontinued. CONCLUSION: Neuropsychiatric evaluation for prior mood or psychiatric disorders in those initiating levetiracetam therapy is suggested alongside monitoring for early features of levetiracetam-induced rage by both caregivers and physicians. This will help stem the morbidity and potential mortality associated with this life-threatening adverse drug reaction. PMID- 26543811 TI - Burst suppression electroencephalogram with mushroom poisoning, Amanita pantherina. AB - We report on a patient with Amanita pantherina poisoning who showed a burst suppression pattern on electroencephalography during a comatose state. The patient recovered without sequelae a week after ingestion. Burst suppression pattern is defined as alternating bursts and periods of electrical silence, and it is associated with comatose states of various causes. The major toxins contained in A. pantherina are ibotenic acid, an excitatory amino acid at the glutamate receptors, and muscimol, an agonist of the gamma-aminobutyric acid receptors. Alteration of the synaptic transmission in the central nervous system by these toxins may lead to a burst suppression pattern. PMID- 26543812 TI - Topiramate-induced hyperammonemic encephalopathy in a patient with mental retardation: A case report and review of the literature. AB - Hyperammonemia is an uncommon side effect of topiramate (TPM) that has only been reported when it is used as an adjunct to valproate. We report a patient with mental retardation who developed reversible encephalopathy from TPM. Ammonia level was monitored during the course of TPM treatment. This patient had recurring, reversible elevations in serum ammonia levels that coincided with the administration of TPM. To our knowledge, symptomatic hyperammonemia has not been reported to occur with TPM monotherapy. PMID- 26543813 TI - Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9. AB - An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9 dependent metabolism seem to play some role in the age-related differences in the incidence of adverse events. We present the case of a premature patient with moderate hemorrhage in the subependymal region (grade II - intraventricular hemorrhage without ventricular dilatation), several myoclonic episodes in her right upper arm (series of jerks lasting milliseconds), and epileptiform abnormalities on the EEG (localized spike-and-wave in the left frontal region with preserved background activity who was treated with valproate. Serious side effects, consisting of bone marrow depression, hyperammonemia, and serum alkaline phosphatase elevation, were observed seventeen days after the beginning of valproate therapy. The toxic symptoms were likely the consequence of a reduced ability to metabolize valproate. The patient was demonstrated to carry two loss of-function mutations in CYP2C9 (CYP2C9*3/*3) resulting in exaggerated blood concentrations of valproate. The present case highlights the importance of assaying inborn errors in CYP2C9 gene in pediatric patients to avoid valproate evoked serious side effects. PMID- 26543814 TI - A subtle case of tuberous sclerosis complex. AB - Tuberous sclerosis complex (TSC) is known to cause severe intractable epilepsy and mental retardation; however, diagnosis can be delayed in milder cases. We report a 26-year-old right-handed female patient who started having convulsions at age 7 days. She had several focal seizures per year that were intractable to treatment with carbamazepine or phenytoin. Her two sisters had several episodes of suspected epileptic seizures but had no symptoms related to TSC. Seizure semiology of the patient comprised of visual hallucination, loss of consciousness, and convulsive movements predominantly on the right. Physical examination revealed several small scattered angiofibromas over the nose that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches, or periungual fibromas were not seen. Neurological examination showed mental retardation (MMSE: 23/30, WAIS-III: VIQ63, PIQ59, FIQ58) and decreased vibration sensation in both legs. Interictal EEG showed slow waves and epileptiform discharges broadly over the anterior quadrants bilaterally. Brain imaging showed multiple cortical tubers and malformation of cortical development but no subependymal nodules. Interictal IMP-SPECT showed hypoperfusion in the left frontal lobe. Cardiac rhabdomyoma was not noticed by cardiac echography. Truncal CT showed sclerosis of the bilateral lumbosacral joints. There was no abnormality in the lung, major arteries, liver, or kidneys. No hamartomas or retinal achromic patches were noticed by ophthalmologic evaluation. Administration of lamotrigine was effective for her seizures. This patient fulfilled two major features of diagnostic criteria for TSC and was diagnosed as definite TSC. Patients with mental retardation and epilepsy should be carefully evaluated for the possible diagnosis of TSC. PMID- 26543816 TI - Does pyridoxine control behavioral symptoms in adult patients treated with levetiracetam? Case series from UAE. AB - Behavioral symptoms are known side effects of levetiracetam. Previous case series in children and adolescents have demonstrated the potential effect of pyridoxine in ameliorating these symptoms. We retrospectively reviewed the charts of 51 patients treated with pyridoxine to control agitation and irritability following the introduction of levetiracetam. These symptoms were relieved in 34 patients (66.6%). Seventeen patients did not appear to benefit from this supplementation. This preliminary study suggests that pyridoxine might be an effective option across all ages for patients suffering from levetiracetam-induced behavioral side effects. PMID- 26543815 TI - A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness. AB - Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted. PMID- 26543817 TI - Surgical treatment of focal symptomatic refractory status epilepticus with and without invasive EEG. AB - PURPOSE: Neurosurgery appears to be a reasonable alternative in carefully selected patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). We discuss the optimal timing of the surgery and the use of previous stereoelectroencephalography (SEEG) invasive evaluation. METHODS: We identified 3 patients (two pediatric and one adult) who underwent epilepsy surgery because of RSE or SRSE from our epilepsy surgery database, one of them with previous SEEG. RESULTS: Status epilepticus resolved acutely in all of them with no mortality and no substantial morbidity. At follow-up (median: 2 years), 1 patient was seizure-free, and 2 had significant improvement. CONCLUSION: Surgery should be considered in all cases of RSE and SRSE early in the course of the evolution of the disease. PMID- 26543818 TI - Automated-immunosensor with centrifugal fluid valves for salivary cortisol measurement. AB - Point-of-care measurement of the stress hormone cortisol will greatly facilitate the timely diagnosis and management of stress-related disorders. We describe an automated salivary cortisol immunosensor, incorporating centrifugal fluid valves and a disposable disc-chip that allows for truncated reporting of cortisol levels (<15 min). The performance characteristics of the immunosensor are optimized through select blocking agents to prevent the non-specific adsorption of proteins; immunoglobulin G (IgG) polymer for the pad and milk protein for the reservoirs and the flow channels. Incorporated centrifugal fluid valves allow for rapid and repeat washings to remove impurities from the saliva samples. An optical reader and laptop computer automate the immunoassay processes and provide easily accessible digital readouts of salivary cortisol measurements. Linear regression analysis of the calibration curve for the cortisol immunosensor showed 0.92 of coefficient of multiple determination, R2, and 38.7% of coefficient of variation, CV, for a range of salivary cortisol concentrations between 0.4 and 11.3 ng/mL. The receiver operating characteristic (ROC) curve analysis of human saliva samples indicate potential utility for discriminating stress disorders and underscore potential application of the biosensor in stress disorders. The performance of our salivary cortisol immunosensor approaches laboratory based tests and allows noninvasive, quantitative, and automated analysis of human salivary cortisol levels with reporting times compatible with point-of-care applications. PMID- 26543820 TI - Mechanisms-based therapeutic strategies in type 2 diabetes. PMID- 26543819 TI - An accurate, precise method for general labeling of extracellular vesicles. AB - Extracellular, membrane vesicles (microvesicles, exosomes) are secreted by cells and may serve as mediators of intercellular communication. Methods for detecting them by flow cytometry have included the use of agents that fluorescently stain vesicle membrane, or fluorescent antibodies that target specific cell-of-origin antigens. However, these methods may falsely detect cell debris or require prior cell-of-origin knowledge. Here, we demonstrate the suitability of calcein AM for detection of intact extracellular vesicles (EVs) by flow cytometry.*Calcein AM is non-fluorescent until it passively enters EVs, after which it is activated and becomes fluorescent and EV-impermeant.*Permeabilized/lysed EVs label positive with antibodies and lipophilic membrane stain, whereas no labeling was observed with calcein. In contrast to methods that use antibodies or membrane stains, calcein AM allows for the differentiation between intact EVs and debris.*Calcein AM can be used for detection of intact EVs from numerous cell types. PMID- 26543821 TI - Mechanisms of ectopic calcification: implications for diabetic vasculopathy. AB - Vascular calcification (VC) is the deposition of calcium/phosphate in the vasculature, which portends a worse clinical outcome and predicts major adverse cardiovascular events. VC is an active process initiated and regulated via a variety of molecular signalling pathways. There are mainly two types of calcifications: the media VC and the intima VC. All major risk factors for cardiovascular disease (CVD) have been linked to the presence/development of VC. Besides the risk factors, a genetic component is also operative to determine arterial calcification. Several events take place before VC is established, including inflammation, trans-differentiation of vascular cells and homing of circulating pro-calcific cells. Diabetes is an important predisposing factor for VC. Compared with non-diabetic subjects, patients with diabetes show increased VC and higher expression of bone-related proteins in the medial layer of the vessels. In this review we will highlight the mechanisms underlying vascular calcification in diabetic patients. PMID- 26543822 TI - Understanding and treating hypertension in diabetic populations. AB - Hypertension and diabetes frequently occurs in the same individuals in clinical practice. Moreover, the presence of hypertension does increase the risk of new onset diabetes, as well as diabetes does promote development of hypertension. Whatever the case, the concomitant presence of these conditions confers a high risk of major cardiovascular complications and promotes the use integrated pharmacological interventions, aimed at achieving the recommended therapeutic targets. While the benefits of lowering abnormal fasting glucose levels in patients with hypertension and diabetes have been consistently demonstrated, the blood pressure (BP) targets to be achieved to get a benefit in patients with diabetes have been recently reconsidered. In the past, randomized clinical trials have, indeed, demonstrated that lowering BP levels to less than 140/90 mmHg was associated to a substantial reduction of the risk of developing macrovascular and microvascular complications in hypertensive patients with diabetes. In addition, epidemiological and clinical reports suggested that "the lower, the better" for BP in diabetes, so that levels of BP even lower than 130/80 mmHg have been recommended. Recent randomized clinical trials, however, designed to evaluate the potential benefits obtained with an intensive antihypertensive therapy, aimed at achieving a target systolic BP level below 120 mmHg as compared to those obtained with less stringent therapy, have challenged the previous recommendations from international guidelines. In fact, detailed analyses of these trials showed a paradoxically increased risk of coronary events, mostly myocardial infarction, in those patients who achieved the lowest BP levels, particularly in the high-risk subsets of hypertensive populations with diabetes. In the light of these considerations, the present article will briefly review the common pathophysiological mechanisms, the potential sites of therapeutic interactions and the currently recommended BP targets to be achieved under pharmacological treatment in hypertension and diabetes. PMID- 26543823 TI - Atrial fibrillation in patients with diabetes: molecular mechanisms and therapeutic perspectives. AB - Atrial fibrillation (AF) remains the most frequent sustained cardiac arrhythmia worldwide and its incidence increases with ageing, cardiovascular risk factors and comorbidities. Prevalence of diabetes mellitus (DM) is growing fast and is assuming pandemic proportions mostly due to overnutrition and sedentary habits. Experimental and clinical evidences suggest that DM and AF are strongly interconnected. The present review addresses in detail new molecular pathways implicated in the etiology of AF and their relevance for mechanism-based therapeutic strategies in this setting. Advances in risk stratification, drug therapy (i.e., novel anticoagulants) and catheter ablation are also described. PMID- 26543825 TI - Diabetic cardiomyopathy: is resistin a culprit? AB - Cardiovascular disease, including heart failure (HF), is the major cause of death in patients with diabetes. A contributing factor to the occurrence of HF in such patients is the development of diabetic cardiomyopathy. Recent evidence demonstrates that perturbations associated with adipokines secretion and signaling result in lusitropic and inotropic defects in diabetic cardiomyopathy. This perspective editorial will discuss the central role of resistin, a recently discovered adipokine, in the maladaptive cardiac phenotype seen in diabetic hearts. Given the pleiotropic effects of resistin, strategies targeting the control of resistin levels may constitute a potentially viable therapeutic utility in patients with diabetes and diabetes-induced cardiovascular diseases. PMID- 26543824 TI - Vascular repair strategies in type 2 diabetes: novel insights. AB - Impaired functions of vascular cells are responsible for the majority of complications in patients with type 2 diabetes (T2D). Recently a better understanding of mechanisms contributing to development of vascular dysfunction and the role of systemic inflammatory activation and functional alterations of several secretory organs, of which adipose tissue has more recently been investigated, has been achieved. Notably, the progression of vascular disease within the context of T2D appears to be driven by a multitude of incremental signaling shifts. Hence, successful therapies need to target several mechanisms in parallel, and over a long time period. This review will summarize the latest molecular strategies and translational developments of cardiovascular therapy in patients with T2D. PMID- 26543827 TI - Hyperglycemia: a bad signature on the vascular system. AB - Experimental work has clearly demonstrated that hyperglycemia is able to derail molecular pathways favouring oxidative stress, inflammation and endothelial dysfunction. Consistently, pooled analyses from prospective studies provide strong evidence that glycemic markers, namely glycated haemoglobin (HbA1c), predict cardiovascular risk, with an increase of about 18% in risk for each 1% absolute increase in HbA1c concentration, regardless of classical risk factors. Although the importance of hyperglycemic burden on cardiovascular phenotype, normalization of blood glucose levels in patients with long-standing hyperglycemia does not seem to reduce macrovascular complications. These data suggest that hyperglycemia may exert long-lasting detrimental effects on the cardiovascular system. This emerging phenomenon is defined metabolic or hyperglycemic memory to indicate a long-term persistence of hyperglycemic stress, even after blood glucose normalization. Here, we discuss clinical evidence and potential molecular mechanisms implicated in metabolic memory and, hence, diabetes-related cardiovascular complications. PMID- 26543826 TI - Boosting autophagy in the diabetic heart: a translational perspective. AB - Diabetes, obesity, and dyslipidemia are main risk factors that promote the development of cardiovascular diseases. These metabolic abnormalities are frequently found to be associated together in a highly morbid clinical condition called metabolic syndrome. Metabolic derangements promote endothelial dysfunction, atherosclerotic plaque formation and rupture, cardiac remodeling and dysfunction. This evidence strongly encourages the elucidation of the mechanisms through which obesity, diabetes, and metabolic syndrome induce cellular abnormalities and dysfunction in order to discover new therapeutic targets and strategies for their prevention and treatment. Numerous studies employing both dietary and genetic animal models of obesity and diabetes have demonstrated that autophagy, an intracellular system for protein degradation, is impaired in the heart under these conditions. This suggests that autophagy reactivation may represent a future potential therapeutic intervention to reduce cardiac maladaptive alterations in patients with metabolic derangements. In fact, autophagy is a critical mechanism to preserve cellular homeostasis and survival. In addition, the physiological activation of autophagy protects the heart during stress, such as acute ischemia, starvation, chronic myocardial infarction, pressure overload, and proteotoxic stress. All these aspects will be discussed in our review article together with the potential ways to reactivate autophagy in the context of obesity, metabolic syndrome, and diabetes. PMID- 26543829 TI - Professor Lawrence H. Cohn: minimally invasive cardiac surgery. PMID- 26543828 TI - Diabetes and cardiovascular disease: let's push forward with translational research. AB - Albeit advances in therapy have reduced morbidity and mortality in patients with diabetes, cardiovascular (CV) risk is far to be eradicated. This is partially due to the fact that breakthrough therapies have yet to be approved to counteract the atherosclerotic burden in this setting. Therefore, it is very important to understand the molecular mechanisms underpinning diabetes-related CV complications. Growing evidence is supporting the concept that translational research is perhaps the best approach to unveil novel insights into disease etiology and its link with CV phenotypes. The recent employment of high throughput "omics" (i.e., metabolomics, transcriptomics, proteomics) is a clinically relevant approach which may provide insightful interpretations of diabetes-related biological signals. The possibility to analyse thousands or more molecules simultaneously has given "omics" the ability to generate enormous quantities of data which may somehow offer a precious "window on the disease". In the present article, we critically discuss the importance of translational research in diabetes, including potential difficulties which may arise in the implementation and development of promising technologies from the laboratory to the marketplace. PMID- 26543830 TI - Clomiphene Effects on Idiopathic Premature Ejaculation. AB - BACKGROUND: Premature ejaculation (PE) is the inability to delay ejaculation, occurring sooner than they or their partner would like during sexual activities. PE is a challenging problem that can affect sexual enjoyment and may harm relationships of couples and affect their quality of life. In idiopathic PE, several helpful techniques and medicines are recommended, but none of them has yielded satisfactory results. OBJECTIVES: Our objective in this study was to evaluate the efficacy and safety of clomiphene as a selective estrogen receptor modulator on the treatment of idiopathic PE. PATIENTS AND METHODS: In a randomized clinical trial, 178 married men with idiopathic PE defined according to the Diagnostic and Statistical Manual of Mental Disorders Third Revised Version (DSM-III-R) who referred to urology clinics over a 10-month period in 2012 were randomized into two groups, namely the study (clomiphene) and control (placebo) groups. They completed self-administered questionnaires that included intravaginal ejaculatory latency time (IELT), erectile dysfunction indexes, quality of life (QOL), sociodemographic characteristics, lifestyle, and medical illness. After 6 months of intervention, all data were compared with the baseline data and between the groups. RESULTS: Within the 10-month study course, 126 patients (70.8%) completed this study. After intervention and comparison of the results between the two groups, IELT, sexual indexes, and QOL improved in the study group, but significant differences were observed only in the IELT and QOL findings. CONCLUSIONS: Clomiphene seems to be useful in the pharmacological treatment of PE compared to the placebo. PMID- 26543831 TI - Use of Silodosin to Visualize the Posterior Urethra in Pelvic Floor Urethral Distraction Defect Patients. AB - BACKGROUND: Retrograde urethrogram and voiding cystourethrogram are used to define length and location of urethral stricture prior to surgery. We used a single dose of silodosin prior to VCUG to relax the bladder neck and achieve visualization of posterior urethra. OBJECTIVES: To evaluate the efficacy of silodosin in visualization of posterior urethra during VCUG, and to compare the findings with a control group. PATIENTS AND METHODS: Patients were divided into two groups A and B containing 20 and 15 patients, respectively. Patients in group A were given a single dose of silodosin prior to radiological studies. RESULTS: In group A 19 out of 20 patients were able to achieve satisfactory bladder neck opening while in group B 10 out of 15 patients were able to achieve bladder neck opening. CONCLUSIONS: Silodosin use prior to VCUG confers a statistically significant increase in bladder neck opening and visualization of posterior urethra. PMID- 26543832 TI - Therapeutic Efficacy of Hydrochlorothiazide in Primary Monosymptomatic Nocturnal Enuresis in Boys With Idiopathic Hypercalciuria. AB - BACKGROUND: Idiopathic hypercalciuria (IHC) can be one of the causes of nocturnal enuresis (NE) and hydrochlorothiazide (HCT) ameliorates hypercalciuria. OBJECTIVES: The aim of this study was to assess the therapeutic efficacy of HCT in boys with primary monosymptomatic NE (PMNE). PATIENTS AND METHODS: This study was a randomized double-blind placebo-controlled clinical trial. A hundred boys with PMNE and IHC were randomly assigned into two groups of experimental (treated with HCT 1 mg/kg/day) and control and all patients were followed for 4 months for the number of wet-night episodes. RESULTS: The mean numbers of wet-night episodes in the first (intervention: 8.34 +/- 8.54, control: 9.1 +/- 9.3, P = 0.3), second (7.1 +/- 7.3, 7.9 +/- 8.1, P = 0.4), third (7.8 +/- 8, 7.9 +/- 8.1, P = 0.1) and fourth (4.9 +/- 5.1, 5.9 +/- 6, P = 0.3) months were not significantly different between the two groups. However, the decrease in the average wet-night episodes during the 4 months of treatment in the intervention group (P = 0.019) unlike the control group. Not more significant compared to control group (P = 0.191). All patients who were treated by HCT became normocalciuric. However, in 21 patients the dose was increased to 2 mg/kg/day. CONCLUSIONS: Single daily dose of HCT is a safe and effective therapeutic option in the treatment of PMNE in children with IHC. PMID- 26543833 TI - Iranian Nephrology and Urology Research Output in the Past Two Decades: A Bibliographic Analysis of Medline Database. AB - CONTEXT: We performed a bibliometric search to evaluate the number of papers published in the field of nephrology and urology by Iranian researchers in the past two decades. EVIDENCE ACQUISITION: We did an online search in abstract/title part of articles with 129 keywords such as kidney, renal, hemodialysis, transplant, nephrology, glomerulonephritis, ureteral, nephrolithiasis, and etc. Endnote software version 7 was used to search articles published in PubMed database from November 1993 to November 2013. Those articles in which Iran was the affiliation of at least one of the authors were selected. These articles in the field of nephrology and urology were analyzed regarding the name of originated institution, field of study, total number of publications, type of study, collaboration rate of Iranian nephrologist and urologists for every year, annual sharing of Iranian articles in five journals with highest impact factor (IF) and journal IF. RESULTS: The total number of publications in the field of nephrology and urology was 3,771 (average of 189 papers per year). Most of the Iranian nephrology and urology papers were from the capital city, Tehran (50.03%). There was an increasing trend in the number of publications over the years. Most papers were about transplantation (44.6%), nephrology (20.9%) and hemodialysis (16.4%). Of all, 53.7% were retrospective articles, whereas the proportion of clinical trials was relatively small (10.8%). CONCLUSIONS: Although Iranian publications in the field of nephrology and urology have had a considerable and significant increase in the recent years amongst the Middle Eastern countries, there is a wide distance to be a science exporter country. PMID- 26543834 TI - Comparison Between the Transobturator Tape Procedure and Anterior Colporrhaphy With the Kelly's Plication in the Treatment of Stress Urinary Incontinence: a Randomized Clinical Trial. AB - BACKGROUND: Stress urinary incontinence in women is a common problem that impairs the quality of life in patients. The extraordinary number of procedures to treat stress urinary incontinence reflects a lack of consensus on an appropriate intervention for this problem. OBJECTIVES: The current study aimed to compare the results of transobturator tape (TOT) procedure and anterior colporrhaphy with the Kelly's Plication to treat women with stress urinary incontinence. PATIENTS AND METHODS: This randomized clinical trial was conducted on 60 patients with stress urinary incontinence referred to Afzalipour Hospital in Kerman, Iran. The patients were randomly divided into two surgery groups and were subsequently assessed regarding the outcomes of the procedures, incontinence symptoms and complications during the follow-up period. RESULTS: The cure rates at follow-up period of one month, six months and one year after surgery were 86.7%, 80% and 80% in the TOT group versus 80%, 70% and 66.7% in the anterior colporrhaphy with the Kelly's Plication group, respectively. There were no significant differences between the two groups in the aforementioned follow-up periods (P = 0.68, P = 0.54 and P = 0.22, respectively). CONCLUSIONS: The current results showed no significant differences between the outcomes of the two procedures at short-term follow-up. However, the results might have changed in the long term. PMID- 26543835 TI - Occult Laryngeal Foreign Body Mimicking Normal Thyroid Cartilage. AB - INTRODUCTION: Foreign body aspiration is common especially in children. The absence of history of choking does not rule out the diagnosis. Diagnosis required high index of suspicion. CASE PRESENTATION: Undiagnosed foreign body aspiration mostly occurs in bronchial airway rather than larynx and can cause severe complications. In this article, we report a silent laryngeal foreign body aspiration to show that careful history taking and accurate evaluation of radiography are important factors for diagnosis. CONCLUSIONS: The single most significant factor leading to detect of tracheobronchial foreign body aspiration is a high index of suspicion; this case highlights the possibility of a foreign body in the airway in patients who presents with a recent onset of chronic respiratory complaints. PMID- 26543836 TI - A Triage Model for Chemical Warfare Casualties. AB - CONTEXT: The main objectives of triage are securing patient safety during the process of emergency diagnosis and treatment, and reduction of waiting time for medical services and transport. To date, there is no triage system for nerve agent victims. EVIDENCE ACQUISITION: This systematic review proposes a new triage system for patients exposed to nerve agents. Information regarding clinical signs and symptoms of intoxication with nerve agents, primary treatments, and classification of patients were extracted from the literature. All related articles were reviewed. Subsequently, specialists from different disciplines were invited to discuss and draft protocols. RESULTS: Finalized triage tables summarizing the classification methods and required protocols in the field were designed after several meetings. CONCLUSIONS: The proposed triage protocol encompasses aspects from most of the existing triage systems to create a single overarching guide for unifying the triage process. The proposed protocol can serve as a base for the designing future guidelines. PMID- 26543837 TI - Displaced Intra-Articular Fractures of the Distal Radius: Open Reduction With Internal Fixation Versus Bridging External Fixation. AB - BACKGROUND: Distal radius fracture is common in all ages. Mobility and wrist function is important. The choice of treatment should aim for optimal function with minimal complications. OBJECTIVES: In this study we compared two surgical approaches, open reduction and internal fixation (ORIF) and closed reduction with external fixation (CR + EF), for treatment of intra-articular distal radius fractures. PATIENTS AND METHODS: Ninety-four patients with distal radius fracture (type 3, 4 and 5 Fernandez classification) were treated with two surgical methods (ORIF and CR + EF); 55 were treated with CR + EF and 39 were treated with ORIF by different surgeons. All patients were assessed at the end of the first, third and sixth week; and then after the third, sixth and 12(th) month. At the end of the follow-up, all patients completed the Michigan hand outcome questionnaire (MHOQ). We compared radiological parameters of distal radius, range of motion (ROM) of the wrist, duration of rehabilitation, complication and patient satisfaction of the methods. RESULTS: In our study, radiological findings for the ORIF group were radial inclination (RI): 19.35, radial length (RL): 10.35, radial tilt (RT): 8.92, and ulnar variance (UV): 1.64, while for the CR + EF group these were RI: 15.13, RL: 8, RT: 4.78, and UV: 0.27. The ROM for ORIF were flexion/extension (F/E): 137, Radial/Ulnar deviation (R/U): 52, and Supination/Pronation (S/P): 141, while for the CR + EF group these were F/E: 117, R/U: 40 and S/P: 116. Michigan hand outcome score for ORIF was 75% and for Ext. fix was 60%. The rate of complication with the ORIF method was 58% and in Ext. fix this was 69%. The patients in CR + EF had more than the ORIF course of physiotherapy and rehabilitation. CONCLUSIONS: In comparison of ORIF and CR + EF, all results including functional score, clinical and radiologic criteria were in favor of the ORIF method while there were less complications with this method. We believe that ORIF is a better method for treatment of these types of fractures. PMID- 26543838 TI - Management of Neglected Traumatic Bilateral Cervical Facet Dislocations Without Neurological Deficit. AB - INTRODUCTION: Sub axial cervical spine dislocations are common and managing these cases by closed reduction is successful in the majority of cases. However, treatment of old and neglected cases is difficult and the results may vary in terms of neurological and functional outcomes. CASE PRESENTATION: We present two cases of traumatic bilateral cervical facet dislocation with no neurological deficit (ND) who referred four months after the injury. They were managed via single stage anterior discectomy, posterior facet reduction, instrumentation, and then anterior reconstruction with bone graft and cervical plate. The patients had no ND in the postoperative period and returned to work. DISCUSSION: Patients presenting with neck pain after a history of trauma should be evaluated thoroughly with radiographs and computed tomography. The management of old neglected facet dislocations is difficult, lengthy, and fraught with potential neurological complications; operative intervention can substantially improve the quality of life in these patients. PMID- 26543839 TI - A Study to Analyses Pattern and Treatment of Upper Cervical Spine Injuries Experience From Developing World. AB - BACKGROUND: The literature regarding the different patterns of upper cervical spine injuries, their appropriate management, and management development of such injuries is scarce in the world. OBJECTIVES: The current study aimed to present the experience regarding the high velocity trauma of upper cervical spine injuries. PATIENTS AND METHODS: Thirty patients (22 males, 8 females) with upper cervical spine injuries were treated and followed-up for an average of 24 months. The corresponding data were analyzed with respect to various types of injuries and different treatment modalities used to treat such patients keeping the basic healthcare facilities in view. RESULTS: The clinical as well as radiological outcomes of the treatment of such injuries were mostly achievable with minimum facilities in India, with only few complications. CONCLUSIONS: Managing such patients needs a proper transport facility, proper care during transport, appropriate evaluation in the hospital and prompt conservative or operative treatment. Treatment is usually safe and effective by well trained professionals with good clinical and radiological outcomes. PMID- 26543840 TI - Presentation of a Humeral Shaft Fracture Treated by Locked Intramedullary Nailing With Unlocked Technique. AB - INTRODUCTION: Although intramedullary nailing (IMN) is used in a reamed or unreamed fashion for treatment of long bone fractures, the locked nails may also be used in the unlocked form if so decided by the orthopedic surgeon. CASE PRESENTATION: We describe a 50-year-old man who had a shaft fracture of his right humerus. The fracture was treated with a reamed, locked IMN using unlocked technique. CONCLUSIONS: The functional outcome 22 months post injury showed that although primary treatment method uses locked IMN in humeral shaft fractures, unlocked IMN can be used in appropriate cases. Less injury risk to the axillary and radial nerve, short period of surgery, and less radiation can be considered as advantages of this technique. PMID- 26543841 TI - Perception From Barrier and Facilitator for Providing Early Rehabilitation Care for RTI Victims. AB - BACKGROUND: Road traffic injuries (RTIs) are a major public health problem and the most important cause of disability, morbidity and mortality worldwide. Early rehabilitation can play a significant role in minimizing complications, morbidity and mortality. OBJECTIVES: The aim of this study was to describe perceptions of barriers precluding provision of early rehabilitation care for RTI victims. PATIENTS AND METHODS: A qualitative content analysis was carried out on 15 nurses with at least one year experience caring for RTI victims. The nurses were selected from various wards (emergency, orthopedic, neurosurgery, and clinic) of Sina and Imam Khomeini Hospitals via targeted sampling. Data were collected through semi-structured interviews and targeted sampling until data saturation. Data were analyzed and assessed. RESULTS: After continuous analysis and comparison of data, major causes precluding nurses from early rehabilitation of RTI patients were retrieved. These barriers included: (a) lack of insight, (b) lack of comprehensive care (c) excessive costs; facilitating factors included (d) training for cooperation and (e) support for coping. CONCLUSIONS: The findings of this study show that the need for early rehabilitation in the hospital phase of care for RTI victims is needed. Knowledge about the barriers precluding nurses from early rehabiltiation of RTI patients and facilitators that can help health care workers and policy makers eliminate the barriers precluding early rehabilitation can help health care workers, especially nurses enable patients get over their disability and gain social and family support. PMID- 26543842 TI - Mechanism of Injury, Glasgow Coma Scale, Age, and Systolic Blood Pressure: A New Trauma Scoring System to Predict Mortality in Trauma Patients. AB - BACKGROUND: Trauma is the most common cause of death in people aged 1 - 44 years and the third leading cause of death regardless of age. Early diagnosis can expedite emergency care and thus patients can be transferred more quickly to a treatment center. OBJECTIVES: The purpose of this study was to evaluate the mechanism of injury, Glasgow coma scale, age, and arterial pressure (MGAP) scoring system in predicting mortality in trauma patients. PATIENTS AND METHODS: In this cross-sectional study, 5,484 victims over 12 years of age referred to a trauma referral hospital and were evaluated. The MGAP score was assessed based on type of injury, Glasgow coma scale (GCS), systolic blood pressure (BP) and patient's age. The area under the receiver operating characteristic (AUROC) curve was used as a measure of predictive performance. Data were analyzed using SPSS software version 16. RESULTS: Patients were divided into three groups : scores of less than 18, 18 - 22 and greater than 22; in which the mortality rates were 75.2%, 9.5% and 0.1%, respectively (P < 0.0001). The best cut-off point was 22 in our study, and the MGAP scoring system had 93.7% sensitivity and 91.3% specificity. CONCLUSIONS: The MGAP scoring system can be used as an appropriate scoring system to predict mortality in triage trauma patients. PMID- 26543843 TI - A Case of Slipped Capital Femoral Epiphysis in Association With Craniopharyngioma. AB - INTRODUCTION: Slipped capital femoral epiphysis is characterized by the slippage of the proximal femoral epiphysis on the metaphysis, which is sometimes associated with an underlying endocrine disorder. Panhypopituitarism due to craniopharyngioma has been reported several times. We report a case of craniopharyngioma recurrence leading to slipped capital femoral epiphysis. CASE PRESENTATION: A 28-year-old man diagnosed with recurrent craniopharyngioma presented with slipped capital femoral epiphysis. He was treated with gentle manipulation, capsulotomy, and placement of one screw as fixation per side. No complications showed up in a follow-up duration of 4 months. CONCLUSIONS: We underscored the importance of endocrinologic disorders in craniopharyngioma cases. Such disorders should be taken into consideration and be followed up. PMID- 26543845 TI - National Getaways for the Weary Trauma Surgeon; Part 4: The Silk Road Trip. PMID- 26543844 TI - Treatment of Humeral Shaft Fractures: Minimally Invasive Plate Osteosynthesis Versus Open Reduction and Internal Fixation. AB - BACKGROUND: The optimal technique for operative fixation of humeral shaft fractures remains controversial and warrants research. OBJECTIVES: The purpose of the current study was to compare the functional and clinical outcomes of conventional open reduction and internal fixation (ORIF) with minimally invasive plate osteosynthesis (MIPO) in patients with fractures in two-third distal humeral shaft. PATIENTS AND METHODS: In the current prospective case-control study, 65 patients with humeral shaft fractures were treated using ORIF (33 patients) or MIPO (32 patients). Time of surgery, time of union, incidence of varus deformity and complications were compared between the two groups. Also, the university of California-Los Angeles (UCLA) shoulder rating scale and Mayo Elbow performance score (MEPS) were used to compare the functional outcomes between the two groups. RESULTS: The median of union time was shorter in the MIPO group (4 months versus 5 months). The time of surgery and functional outcomes based on the UCLA and MEPS scores were the same. The incidence of varus deformity was more than 5 degrees and was higher and the incidence of nonunion, infection and iatrogenic radial nerve injury were lower in the MIPO group; however, the differences were not significant. CONCLUSIONS: Due to the shorter union time, to some extent less complication rate and comparable functional and clinical results, the authors recommend to use the MIPO technique in treating the mid distal humeral shaft fracture. PMID- 26543846 TI - Genome-Wide Identification of Genes Probably Relevant to the Uniqueness of Tea Plant (Camellia sinensis) and Its Cultivars. AB - Tea (Camellia sinensis) is a popular beverage all over the world and a number of studies have focused on the genetic uniqueness of tea and its cultivars. However, molecular mechanisms underlying these phenomena are largely undefined. In this report, based on expression data available from public databases, we performed a series of analyses to identify genes probably relevant to the uniqueness of C. sinensis and two of its cultivars (LJ43 and ZH2). Evolutionary analyses showed that the evolutionary rates of genes involved in the pathways were not significantly different among C. sinensis, C. oleifera, and C. azalea. Interestingly, a number of gene families, including genes involved in the pathways synthesizing iconic secondary metabolites of tea plant, were significantly upregulated, expressed in C. sinensis (LJ43) when compared to C. azalea, and this may partially explain its higher content of flavonoid, theanine, and caffeine. Further investigation showed that nonsynonymous mutations may partially contribute to the differences between the two cultivars of C. sinensis, such as the chlorina and higher contents of amino acids in ZH2. Genes identified as candidates are probably relevant to the uniqueness of C. sinensis and its cultivars should be good candidates for subsequent functional analyses and marker assisted breeding. PMID- 26543847 TI - Analysis of Polygala tenuifolia Transcriptome and Description of Secondary Metabolite Biosynthetic Pathways by Illumina Sequencing. AB - Radix polygalae, the dried roots of Polygala tenuifolia and P. sibirica, is one of the most well-known traditional Chinese medicinal plants. Radix polygalae contains various saponins, xanthones, and oligosaccharide esters and these compounds are responsible for several pharmacological properties. To provide basic breeding information, enhance molecular biological analysis, and determine secondary metabolite biosynthetic pathways of P. tenuifolia, we applied Illumina sequencing technology and de novo assembly. We also applied this technique to gain an overview of P. tenuifolia transcriptome from samples with different years. Using Illumina sequencing, approximately 67.2% of unique sequences were annotated by basic local alignment search tool similarity searches against public sequence databases. We classified the annotated unigenes by using Nr, Nt, GO, COG, and KEGG databases compared with NCBI. We also obtained many candidates CYP450s and UGTs by the analysis of genes in the secondary metabolite biosynthetic pathways, including putative terpenoid backbone and phenylpropanoid biosynthesis pathway. With this transcriptome sequencing, future genetic and genomics studies related to the molecular mechanisms associated with the chemical composition of P. tenuifolia may be improved. Genes involved in the enrichment of secondary metabolite biosynthesis-related pathways could enhance the potential applications of P. tenuifolia in pharmaceutical industries. PMID- 26543848 TI - Goal-Directed Resuscitation Aiming Cardiac Index Masks Residual Hypovolemia: An Animal Experiment. AB - The aim of this study was to compare stroke volume (SVI) to cardiac index (CI) guided resuscitation in a bleeding-resuscitation experiment. Twenty six pigs were randomized and bled in both groups till baseline SVI (T bsl) dropped by 50% (T 0), followed by resuscitation with crystalloid solution until initial SVI or CI was reached (T 4). Similar amount of blood was shed but animals received significantly less fluid in the CI-group as in the SVI-group: median = 900 (interquartile range: 850-1780) versus 1965 (1584-2165) mL, p = 0.02, respectively. In the SVI-group all variables returned to their baseline values, but in the CI-group animals remained underresuscitated as indicated by SVI, heart rate (HR) and stroke volume variation (SVV), and central venous oxygen saturation (ScvO2) at T 4 as compared to T bsl: SVI = 23.8 +/- 5.9 versus 31.4 +/- 4.7 mL, HR: 117 +/- 35 versus 89 +/- 11/min SVV: 17.4 +/- 7.6 versus 11.5 +/- 5.3%, and ScvO2: 64.1 +/- 11.6 versus 79.2 +/- 8.1%, p < 0.05, respectively. Our results indicate that CI-based goal-directed resuscitation may result in residual hypovolaemia, as bleeding caused stress induced tachycardia "normalizes" CI, without restoring adequate SVI. As the SVI-guided approach normalized most hemodynamic variables, we recommend using SVI instead of CI as the primary goal of resuscitation during acute bleeding. PMID- 26543849 TI - Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine. AB - This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 ug/kg/h). Hemodynamic parameters (arterial pressure, heart rate, cardiac output, stroke volume variability, left ventricular contractility, systemic vascular resistance, and central venous pressure), vasoactive drug parameters (dose and time of norepinephrine and hourly fluid intake), pulmonary function (partial oxygen pressure and vascular permeability), and cytokines (interleukin-6 and interleukin-10) were observed. Treatment resulted in significant changes at 4-6 h. HVHF was beneficial, as shown by the dose of vasoactive drugs, fluid intake volume, left ventricular contractility index, and partial oxygen pressure. Both CRRT and HVHF groups showed improved removal of inflammatory mediators compared with controls. In conclusion, EFR combined with HVHF improved septic shock in this swine model. The combination decreased shock progression, reduced the need for vasoactive drugs, and alleviated the damage to cardiopulmonary functions. PMID- 26543851 TI - Cancer Diagnostic and Predictive Biomarkers 2015. PMID- 26543850 TI - Physiological and Neural Adaptations to Eccentric Exercise: Mechanisms and Considerations for Training. AB - Eccentric exercise is characterized by initial unfavorable effects such as subcellular muscle damage, pain, reduced fiber excitability, and initial muscle weakness. However, stretch combined with overload, as in eccentric contractions, is an effective stimulus for inducing physiological and neural adaptations to training. Eccentric exercise-induced adaptations include muscle hypertrophy, increased cortical activity, and changes in motor unit behavior, all of which contribute to improved muscle function. In this brief review, neuromuscular adaptations to different forms of exercise are reviewed, the positive training effects of eccentric exercise are presented, and the implications for training are considered. PMID- 26543852 TI - Wheelchair Propulsion Biomechanics in Junior Basketball Players: A Method for the Evaluation of the Efficacy of a Specific Training Program. AB - As participation in wheelchair sports increases, the need of quantitative assessment of biomechanical performance indicators and of sports- and population specific training protocols has become central. The present study focuses on junior wheelchair basketball and aims at (i) proposing a method to identify biomechanical performance indicators of wheelchair propulsion using an instrumented in-field test and (ii) developing a training program specific for the considered population and assessing its efficacy using the proposed method. Twelve athletes (10 M, 2 F, age = 17.1 +/- 2.7 years, years of practice = 4.5 +/- 1.8) equipped with wheelchair- and wrist-mounted inertial sensors performed a 20 metre sprint test. Biomechanical parameters related to propulsion timing, progression force, and coordination were estimated from the measured accelerations and used in a regression model where the time to complete the test was set as dependent variable. Force- and coordination-related parameters accounted for 80% of the dependent variable variance. Based on these results, a training program was designed and administered for three months to six of the athletes (the others acting as control group). The biomechanical indicators proved to be effective in providing additional information about the wheelchair propulsion technique with respect to the final test outcome and demonstrated the efficacy of the developed program. PMID- 26543853 TI - Decreased Splenic CD4(+) T-Lymphocytes in Apolipoprotein M Gene Deficient Mice. AB - Spleen T-lymphocytes, especially CD4(+) T-cells, have been demonstrated to be involved in broad immunomodulation and host-defense activity in vivo. Apolipoprotein M gene (apoM) may have an important role in the regulation of immunoprocess and inflammation, which could be hypothesized to the apoM containing sphingosine-1-phosphate (S1P). In the present study we demonstrate that the splenic CD4(+) T-lymphocytes were obviously decreased in the apoM gene deficient (apoM(-/-)) mice compared to the wild type (apoM(+/+)). Moreover, these mice were treated with lipopolysaccharide (LPS) and it was found that even more pronounced decreasing CD4(+) T-lymphocytes occurred in the spleen compared to the apoM(+/+) mice. The similar phenomena were found in the ratio of CD4(+)/CD8(+) T lymphocytes. After administration of LPS, the hepatic mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1) were markedly increased; however, there were no statistical differences observed between apoM(+/+) mice and apoM(-/-) mice. The present study demonstrated that apoM might facilitate the maintenance of CD4(+) T-lymphocytes or could modify the T-lymphocytes subgroups in murine spleen, which may further explore the importance of apoM in the regulation of the host immunomodulation, although the detailed mechanism needs continuing investigation. PMID- 26543854 TI - OperomeDB: A Database of Condition-Specific Transcription Units in Prokaryotic Genomes. AB - Background. In prokaryotic organisms, a substantial fraction of adjacent genes are organized into operons-codirectionally organized genes in prokaryotic genomes with the presence of a common promoter and terminator. Although several available operon databases provide information with varying levels of reliability, very few resources provide experimentally supported results. Therefore, we believe that the biological community could benefit from having a new operon prediction database with operons predicted using next-generation RNA-seq datasets. Description. We present operomeDB, a database which provides an ensemble of all the predicted operons for bacterial genomes using available RNA-sequencing datasets across a wide range of experimental conditions. Although several studies have recently confirmed that prokaryotic operon structure is dynamic with significant alterations across environmental and experimental conditions, there are no comprehensive databases for studying such variations across prokaryotic transcriptomes. Currently our database contains nine bacterial organisms and 168 transcriptomes for which we predicted operons. User interface is simple and easy to use, in terms of visualization, downloading, and querying of data. In addition, because of its ability to load custom datasets, users can also compare their datasets with publicly available transcriptomic data of an organism. Conclusion. OperomeDB as a database should not only aid experimental groups working on transcriptome analysis of specific organisms but also enable studies related to computational and comparative operomics. PMID- 26543855 TI - Intraoperative Hemorrhage and Postoperative Sequelae after Intraoral Vertical Ramus Osteotomy to Treat Mandibular Prognathism. AB - Objective. To investigate the factors affecting intraoperative hemorrhage and postoperative sequelae after orthognathic surgery. Materials and Methods. Eighty patients with mandibular prognathism underwent surgical mandibular setback with intraoral vertical ramus osteotomy (IVRO). The correlation between the blood loss volume and postoperative VAS with the gender, age, and operating time was assessed using the t-test and Spearman rank correlation coefficient. The correlation between the magnitude of mandibular setback with the presence of TMJ clicking symptoms and lip sensation was also assessed. Results. The mean operating time and blood loss volume for men and women were 249.52 min and 229.39 min, and 104.03 mL and 86.12 mL, respectively. The mean VAS in men and women was 3.21 and 2.93, and 1.79 and 1.32 on the first and second postoperative days. There is no gender difference in the operating time, blood loss, VAS, TMJ symptoms, and lip numbness. The magnitude of mandibular setback was not correlated with immediate and long-term postoperative lip numbness. Conclusion. There are no gender differences in the intraoperative hemorrhage and postoperative sequelae (pain, lip numbness, and TMJ symptoms). In addition, neither symptom was significantly correlated with the amount of mandibular setback. PMID- 26543856 TI - Occurrence, Persistence, and Virulence Potential of Listeria ivanovii in Foods and Food Processing Environments in the Republic of Ireland. AB - The aim of this study was to assess the occurrence of L. ivanovii in foods and food processing environments in Ireland, to track persistence, and to characterize the disease causing potential of the isolated strains. A total of 2,006 samples (432 food samples and 1,574 environmental swabs) were collected between March 2013 and March 2014 from 48 food business operators (FBOs) belonging to different production sectors (dairy, fish, meat, and fresh-cut vegetable). Six of the forty-eight FBOs had samples positive for L. ivanovii on at least one sampling occasion. L. ivanovii was present in fifteen samples (fourteen environmental samples and one food sample). All but one of those positive samples derived from the dairy sector, where L. ivanovii prevalence was 1.7%. Six distinguishable pulsotypes were obtained by PFGE analysis, with one pulsotype being persistent in the environment of a dairy food business. Sequence analysis of the sigB gene showed that fourteen isolates belonged to L. ivanovii subsp. londoniensis, while only one isolate was L. ivanovii subsp. ivanovii. Cell invasion assays demonstrated that the majority of L. ivanovii strains were comparable to L. monocytogenes EGDe in their ability to invade CACO-2 epithelial cells whilst four isolates had significantly higher invasion efficiencies. PMID- 26543857 TI - Predicting Drug-Target Interactions via Within-Score and Between-Score. AB - Network inference and local classification models have been shown to be useful in predicting newly potential drug-target interactions (DTIs) for assisting in drug discovery or drug repositioning. The idea is to represent drugs, targets, and their interactions as a bipartite network or an adjacent matrix. However, existing methods have not yet addressed appropriately several issues, such as the powerless inference in the case of isolated subnetworks, the biased classifiers derived from insufficient positive samples, the need of training a number of local classifiers, and the unavailable relationship between known DTIs and unapproved drug-target pairs (DTPs). Designing more effective approaches to address those issues is always desirable. In this paper, after presenting better drug similarities and target similarities, we characterize each DTP as a feature vector of within-scores and between-scores so as to hold the following superiorities: (1) a uniform vector of all types of DTPs, (2) only one global classifier with less bias benefiting from adequate positive samples, and (3) more importantly, the visualized relationship between known DTIs and unapproved DTPs. The effectiveness of our approach is finally demonstrated via comparing with other popular methods under cross validation and predicting potential interactions for DTPs under the validation in existing databases. PMID- 26543858 TI - Contribution of Avian Salmonella enterica Isolates to Human Salmonellosis Cases in Constantine (Algeria). AB - An epidemiological investigation was carried out on one hundred Salmonella isolates from broiler farms, slaughterhouses, and human patients in the Constantine region of Algeria, in order to explore the contribution of avian strains to human salmonellosis cases in this region over the same period of time. The isolates were characterized by phenotypic as well as genotypic methods. A large variety of antimicrobial resistance profiles was found among human isolates, while only seven profiles were found among avian isolates. Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR), Insertion Sequence 200-PCR (IS200-PCR), and Pulsed Field Gel Electrophoresis (PFGE) resulted in the allocation of the isolates to 16, 20, and 34 different profiles, respectively. The 3 genotyping methods led to complementary results by underlining the clonality of some serovars with the diffusion and persistence of a single clone in the Constantine area as well as stressing the polymorphism present in isolates belonging to other serovars, indicating the diversity of potential reservoirs of nontyphoidal Salmonella. Altogether, our results seem to indicate that nontyphoidal avian Salmonella may play an important role in human salmonellosis in the Constantine region. PMID- 26543859 TI - Efficient and Specific Detection of Salmonella in Food Samples Using a stn-Based Loop-Mediated Isothermal Amplification Method. AB - The Salmonella enterotoxin (stn) gene exhibits high homology among S. enterica serovars and S. bongori. A set of 6 specific primers targeting the stn gene were designed for detection of Salmonella spp. using the loop-mediated isothermal amplification (LAMP) method. The primers amplified target sequences in all 102 strains of 87 serovars of Salmonella tested and no products were detected in 57 non-Salmonella strains. The detection limit in pure cultures was 5 fg DNA/reaction when amplified at 65 degrees C for 25 min. The LAMP assay could detect Salmonella in artificially contaminated food samples as low as 220 cells/g of food without a preenrichment step. However, the sensitivity was increased 100 fold (~2 cells/g) following 5 hr preenrichment at 35 degrees C. The LAMP technique, with a preenrichment step for 5 and 16 hr, was shown to give 100% specificity with food samples compared to the reference culture method in which 67 out of 90 food samples gave positive results. Different food matrixes did not interfere with LAMP detection which employed a simple boiling method for DNA template preparation. The results indicate that the LAMP method, targeting the stn gene, has great potential for detection of Salmonella in food samples with both high specificity and high sensitivity. PMID- 26543860 TI - Sequence-Based Prediction of RNA-Binding Proteins Using Random Forest with Minimum Redundancy Maximum Relevance Feature Selection. AB - The prediction of RNA-binding proteins is one of the most challenging problems in computation biology. Although some studies have investigated this problem, the accuracy of prediction is still not sufficient. In this study, a highly accurate method was developed to predict RNA-binding proteins from amino acid sequences using random forests with the minimum redundancy maximum relevance (mRMR) method, followed by incremental feature selection (IFS). We incorporated features of conjoint triad features and three novel features: binding propensity (BP), nonbinding propensity (NBP), and evolutionary information combined with physicochemical properties (EIPP). The results showed that these novel features have important roles in improving the performance of the predictor. Using the mRMR-IFS method, our predictor achieved the best performance (86.62% accuracy and 0.737 Matthews correlation coefficient). High prediction accuracy and successful prediction performance suggested that our method can be a useful approach to identify RNA-binding proteins from sequence information. PMID- 26543861 TI - Effects of Exercise Training on Autonomic Function in Chronic Heart Failure: Systematic Review. AB - Objectives. Cardiac autonomic imbalance accompanies the progression of chronic heart failure (CHF). It is unclear whether exercise training could modulate autonomic control in CHF. This study aimed to review systematically the effects of exercise training on heart rate recovery (HRR) and heart rate variability (HRV) in patients with CHF. Methods. Literatures were systematically searched in electronic databases and relevant references. Only published randomized controlled trials (RCTs) focusing on exercise training for CHF were eligible for inclusion. Outcome measurements included HRR and HRV parameters. Results. Eight RCTs were eligible for inclusion and provided data on 280 participants (186 men). The participants were 52-70 years of age with New York Heart Association functional class II-III of CHF. Each study examined either aerobic or resistance exercise. Two trials addressed outcome of HRR and six HRV among these studies. Two RCTs showed that moderate aerobic exercise could improve HRR at 2 minutes after exercise training in CHF. Five of six RCTs demonstrated positive effects of exercise training on HRV which revealed the increments in high frequency (HF) and decrements in LF (low frequency)/HF ratio after training. Conclusion. Participation in an exercise training program has positive effects on cardiac autonomic balance in patients with CHF. PMID- 26543862 TI - Effects of Light Intensity Activity on CVD Risk Factors: A Systematic Review of Intervention Studies. AB - The effects of light intensity physical activity (LIPA) on cardiovascular disease (CVD) risk factors remain to be established. This review summarizes the effects of LIPA on CVD risk factors and CVD-related markers in adults. A systematic search of four electronic databases (PubMed, Academic Search Complete, SPORTDiscus, and CINAHL) examining LIPA and CVD risk factors (body composition, blood pressure, glucose, insulin, glycosylated hemoglobin, and lipid profile) and CVD-related markers (maximal oxygen uptake, heart rate, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and tumor necrosis factor receptors 1 and 2) published between 1970 and 2015 was performed on 15 March 2015. A total of 33 intervention studies examining the effect of LIPA on CVD risk factors and markers were included in this review. Results indicated that LIPA did not improve CVD risk factors and CVD-related markers in healthy individuals. LIPA was found to improve systolic and diastolic blood pressure in physically inactive populations with a medical condition. Reviewed studies show little support for the role of LIPA to reduce CVD risk factors. Many of the included studies were of low to fair study quality and used low doses of LIPA. Further studies are needed to establish the value of LIPA in reducing CVD risk. PMID- 26543864 TI - Assessment of the Knowledge and Attitudes of Saudi Mothers towards Newborn Screening. AB - OBJECTIVE: To assess the attitude and knowledge of the Saudi mothers toward newborn screening (NBS) program. METHODS: A total of 425 Saudi women (only mothers who have at least one pregnancy) participated in the study from different regions in Saudi Arabia and completed the structured questionnaire which sought their views on the NBS services. RESULTS: A majority of the participating women (91.1%) supported the NBS program and felt it was very important and useful. However, knowledge of NBS was found to be very limited and only 34.6% knew that NBS was a test to detect genetic disorders. A lack of communication and counseling to NBS clients by health authorities offering screening is implied. CONCLUSION: In general, there is a positive attitude towards the NBS program among Saudi women. However, they have several concerns to improve the availability of medication and formulas, genetic counseling, medical interventions, communication, education materials, and awareness. PMID- 26543863 TI - Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions. AB - BACKGROUND: 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. OBJECTIVES: To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. METHODS: Twenty healthy recreational 2C-B users (12 women) self administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech), subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires), and cardiovascular effects (blood pressure and heart rate). Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. CONCLUSIONS: The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties. PMID- 26543865 TI - Anagrus breviphragma Soyka Short Distance Search Stimuli. AB - Anagrus breviphragma Soyka (Hymenoptera: Mymaridae) successfully parasitises eggs of Cicadella viridis (L.) (Homoptera: Cicadellidae), embedded in vegetal tissues, suggesting the idea of possible chemical and physical cues, revealing the eggs presence. In this research, three treatments were considered in order to establish which types of cue are involved: eggs extracted from leaf, used as a control, eggs extracted from leaf and cleaned in water and ethanol, used to evaluate the presence of chemicals soluble in polar solvents, and eggs extracted from leaf and covered with Parafilm (M), used to avoid physical stimuli due to the bump on the leaf surface. The results show that eggs covered with Parafilm present a higher number of parasitised eggs and a lower probing starting time with respect to eggs washed with polar solvents or eggs extracted and untreated, both when the treatments were singly tested or when offered in sequence, independently of the treatment position. These results suggest that the exploited stimuli are not physical due to the bump but chemicals that can spread in the Parafilm, circulating the signal on the whole surface, and that the stimuli that elicit probing and oviposition are not subjected to learning. PMID- 26543866 TI - The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. AB - HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option. PMID- 26543867 TI - Construction of Pancreatic Cancer Classifier Based on SVM Optimized by Improved FOA. AB - A novel method is proposed to establish the pancreatic cancer classifier. Firstly, the concept of quantum and fruit fly optimal algorithm (FOA) are introduced, respectively. Then FOA is improved by quantum coding and quantum operation, and a new smell concentration determination function is defined. Finally, the improved FOA is used to optimize the parameters of support vector machine (SVM) and the classifier is established by optimized SVM. In order to verify the effectiveness of the proposed method, SVM and other classification methods have been chosen as the comparing methods. The experimental results show that the proposed method can improve the classifier performance and cost less time. PMID- 26543868 TI - Protective Effect of Intravenous High Molecular Weight Polyethylene Glycol on Fatty Liver Preservation. AB - Ischemia reperfusion injury (IRI) leads to significant tissue damage in liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proved their effectiveness against IRI. The objective of our study was to investigate the potential protective effects of intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) in steatotic livers subjected to cold ischemia reperfusion. In this study, we used isolated perfused rat liver model to assess the effects of PEG 35 intravenous administration after prolonged cold ischemia (24 h, 4 degrees C) and after reperfusion (2 h, 37 degrees C). Liver injury was measured by transaminases levels and mitochondrial damage was determined by confocal microscopy assessing mitochondrial polarization (after cold storage) and by measuring glutamate dehydrogenase activity (after reperfusion). Also, cell signaling pathways involved in the physiopathology of IRI were assessed by western blot technique. Our results show that intravenous administration of PEG 35 at 10 mg/kg ameliorated liver injury and protected the mitochondria. Moreover, PEG 35 administration induced a significant phosphorylation of prosurvival protein kinase B (Akt) and activation of cytoprotective factors e-NOS and AMPK. In conclusion, intravenous PEG 35 efficiently protects steatotic livers exposed to cold IRI. PMID- 26543869 TI - Acute Cardioembolic and Thrombotic Middle Cerebral Artery Occlusions Have Different Morphological Susceptibility Signs on T2 (*) -Weighted Magnetic Resonance Images. AB - Presence of susceptibility sign on middle cerebral artery (MCA) in T2 (*) weighted magnetic resonance (MR) images has been reported to detect acute MCA thromboembolic occlusion. However, the pathophysiologic course of thrombotic MCA occlusion differs from embolic occlusion, which might induce different imaging characters. Our study found that the occurrence rate of the MCA susceptibility sign in cardioembolism (CE) patients was significantly higher than in large artery atherosclerosis (LAA) patients, and the diameter of the MCA susceptibility sign for CE was greater than for LAA. Moreover, the patients with hemorrhagic transformation had MCA susceptibility signs with a significant larger mean diameter than patients without hemorrhagic transformation. Therefore, we hypothesized that the morphology of susceptibility signs could be used to differentiate acute cardioembolic and thrombotic MCA occlusions, which helped to select appropriate treatment strategies for different patients. PMID- 26543870 TI - Population Diversity of Campylobacter jejuni in Poultry and Its Dynamic of Contamination in Chicken Meat. AB - This study aimed to analyse the diversity of the Campylobacter jejuni population in broilers and to evaluate the major source of contamination in poultry meat. Eight rearing cycles over one year provided samples from three different broiler farms processed at the same slaughterhouse. A total of 707 C. jejuni were isolated from cloacal swabs before slaughter and from the breast skin of carcasses after slaughter and after chilling. All suspected Campylobacter colonies were identified with PCR assays and C. jejuni was genotyped by sequence analysis of the flaA short variable region (SVR) and by pulsed-field gel electrophoresis (PFGE) using SmaI enzyme. Phenotypic antibiotic resistance profiles were also assayed using minimal inhibitory concentration (MIC). The flocks carried many major C. jejuni clones possibly carrying over the rearing cycles, but cross contamination between farms may happen. Many isolates were resistant to fluoroquinolones, raising an issue of high public concern. Specific Campylobacter populations could be harboured within each poultry farm, with the ability to contaminate chickens during each new cycle. Thus, although biosecurity measures are applied, with a persistent source of contamination, they cannot be efficient. The role of the environment needs further investigation to better address strategies to control Campylobacter. PMID- 26543872 TI - Improving Performance of Clinical Research: Development and Interest of Electronic Health Records. PMID- 26543871 TI - RNAseq by Total RNA Library Identifies Additional RNAs Compared to Poly(A) RNA Library. AB - The most popular RNA library used for RNA sequencing is the poly(A) captured RNA library. This library captures RNA based on the presence of poly(A) tails at the 3' end. Another type of RNA library for RNA sequencing is the total RNA library which differs from the poly(A) library by capture method and price. The total RNA library costs more and its capture of RNA is not dependent on the presence of poly(A) tails. In practice, only ribosomal RNAs and small RNAs are washed out in the total RNA library preparation. To evaluate the ability of detecting RNA for both RNA libraries we designed a study using RNA sequencing data of the same two breast cancer cell lines from both RNA libraries. We found that the RNA expression values captured by both RNA libraries were highly correlated. However, the number of RNAs captured was significantly higher for the total RNA library. Furthermore, we identify several subsets of protein coding RNAs that were not captured efficiently by the poly(A) library. One of the most noticeable is the histone-encode genes, which lack the poly(A) tail. PMID- 26543873 TI - Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies. AB - Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases. PMID- 26543874 TI - Antitumor Responses of Invariant Natural Killer T Cells. AB - Natural killer T (NKT) cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT) cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies. PMID- 26543875 TI - Chemokine Receptor Expression on Normal Blood CD56(+) NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population. AB - Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56(+low) CD16(+) and CD56(+high) CD16(-/+low) NK-cells. Conventional CD56(+low) and CD56(+high) NK cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56(+low) NK-cells are mainly CXCR1/CXCR2(+) and CXCR3/CCR5(-/+), whereas mostly CD56(+high) NK-cells are CXCR1/CXCR2(-) and CXCR3/CCR5(+). Both NK-cell subsets have variable CXCR4 expression and are CCR4( ) and CCR6(-). The CKR repertoire of the CD56(+low) NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56(+high) NK-cells mimics that of Th1(+) T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56(+int) NK-cells. These NK-cells are CXCR3/CCR5(+), they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57(-) and CD158a(-). In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56(+high) and CD56(+low) NK-cells populations. PMID- 26543877 TI - Psychometric Properties of the Modified Posttraumatic Stress Disorder Symptom Scale among Women with Posttraumatic Stress Disorder and Substance Use Disorders Receiving Outpatient Group Treatments. AB - OBJECTIVE: The use of psychometrically sound measures to assess and monitor PTSD treatment response over time is critical for better understanding the relationship between PTSD symptoms and Substance Use Disorder (SUD) symptoms throughout treatment. We examined the psychometric properties of the Modified Posttraumatic Stress Disorder (PTSD) Symptom Scale, Self-Report (MPSS-SR). METHODS: Three hundred fifty three women diagnosed with co-occurring PTSD (full or sub-threshold) and SUD who participated in a multisite treatment trial completed the MPSS-SR at pre-treatment, weekly during treatment, and posttreatment. Reliability and validity analyses were applied to the data. RESULTS: Internal consistency was excellent throughout the course of the trial demonstrating the MPSS-SR's high reliability. Strong correlations between MPSS-SR scores and the Brief Symptom Inventory and the Clinician Administered PTSD Scale (CAPS) severity scores demonstrated the MPSS-SR's convergent and concurrent validity. We conducted a classification analysis at posttreatment and compared the MPSS-SR at various cutoff scores with the CAPS diagnosis. A cutoff score of 29 on the MPSS-SR yielded a sensitivity rate of 89%, a specificity rate of 77%, and an overall classification rate of 80%, indicating the measure's robust ability to accurately identify individuals with PTSD in our sample at posttreatment. CONCLUSIONS: Findings support the use of the MPSS-SR as a reliable and valid tool to assess and monitor changes in PTSD symptoms over the course of treatment and as an alternative to structured clinical interviews to assess PTSD symptoms among populations with SUDs. PMID- 26543878 TI - The Intersecting Epidemics of Human Immunodeficiency Virus, Community-Associated Methicillin-Resistant Staphylococcus aureus, and Incarceration. AB - Community-associated methicillin-resistant Staphylococcus aureus (MRSA) has had a significant impact on human immunodeficiency virus (HIV)-infected and incarcerated individuals. We examined electronic medical surveillance data from 2006 to 2011 and observed that even in a population of currently or recently incarcerated individuals, HIV status was a significant risk factor for MRSA infections and Hispanic ethnicity was protective. PMID- 26543879 TI - Data for rapid ethanol production at elevated temperatures by engineered thermotolerant Kluyveromyces marxianus via the NADP(H)-preferring xylose reductase-xylitol dehydrogenase pathway. AB - A thermo-tolerant NADP(H)-preferring xylose pathway was constructed in Kluyveromyces marxianus for ethanol production with xylose at elevated temperatures (Zhang et al., 2015 [25]). Ethanol production yield and efficiency was enhanced by pathway engineering in the engineered strains. The constructed strain, YZJ088, has the ability to co-ferment glucose and xylose for ethanol and xylitol production, which is a critical step toward enabling economic biofuel production from lignocellulosic biomass. This study contains the fermentation results of strains using the metabolic pathway engineering procedure. The ethanol producing abilities of various yeast strains under various conditions were compared, and strain YZJ088 showed the highest production and fastest productivity at elevated temperatures. The YZJ088 xylose fermentation results indicate that it fermented well with xylose at either low or high inoculum size. When fermented with an initial cell concentration of OD600=15 at 37 degrees C, YZJ088 consumed 200 g/L xylose and produced 60.07 g/L ethanol; when the initial cell concentration was OD600=1 at 37 degrees C, YZJ088 consumed 98.96 g/L xylose and produced 33.55 g/L ethanol with a productivity of 0.47 g/L/h. When fermented with 100 g/L xylose at 42 degrees C, YZJ088 produced 30.99 g/L ethanol with a productivity of 0.65 g/L/h, which was higher than that produced at 37 degrees C. PMID- 26543880 TI - Transcriptome analysis and characterisation of gill-expressed carbonic anhydrase and other key osmoregulatory genes in freshwater crayfish Cherax quadricarinatus. AB - The pH and salinity balance mechanisms of crayfish are controlled by a set of transport-related genes. We identified a set of the genes from the gill transcriptome from a freshwater crayfish Cherax quadricarinatus using the Illumina NGS-sequencing technology. We identified and characterized carbonic anhydrase (CA) genes and some other key genes involved in systematic acid-base balance and osmotic/ionic regulation. We also examined expression patterns of some of these genes across different sublethal pH levels [1]. A total of 72,382,710 paired-end Illumina reads were assembled into 36,128 contigs with an average length of 800 bp. About 37% of the contigs received significant BLAST hits and 22% were assigned gene ontology terms. These data will assist in further physiological-genomic studies in crayfish. PMID- 26543876 TI - Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage. AB - Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulated ex vivo in order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile. PMID- 26543881 TI - Hydrophilic compounds in liquids of enzymatic hydrolyzed spruce and pine biomass. AB - Organic acids are used for starting compounds in material sciences and in biorefinery, food, fuel, pharmaceutical, and medical industry. Here, we provide the data from a biochemical approach made to investigate production of organic acids and isolation of metals from wood, which is the most abundant biomass. Spruce and bark, phloem, and heartwood from pine were fermented with either microbes of oyster mushroom (Pleurotus ostreatus), baker's yeast, or lactic acid bacteria to improve selective fermentation. Using capillary electrophoresis and liquid chromatography techniques, we identified 14 different organic acids and phenolic acids with good yields. With inductively coupled plasma atomic emission spectroscopy 11 metals were quantified and further detailed analysis/results from these data are available in Siren et al. (2015) [1]. PMID- 26543882 TI - Guided extracellular matrix formation from fibroblast cells cultured on bio inspired configurable multiscale substrata. AB - Engineering complex extracellular matrix (ECM) is an important challenge for cell and tissue engineering applications as well as for understanding fundamental cell biology. We developed the methodology for fabrication of precisely controllable multiscale hierarchical structures using capillary force lithography in combination with original wrinkling technique for the generation of well-defined native ECM-like platforms by culturing fibroblast cells on the multiscale substrata [1]. This paper provides information on detailed characteristics of polyethylene glycol-diacrylate multiscale substrata. In addition, a possible model for guided extracellular matrix formation from fibroblast cells cultured on bio-inspired configurable multiscale substrata is proposed. PMID- 26543883 TI - Mortality due to Japanese oak wilt disease and surrounding forest compositions. AB - Japanese oak wilt (Raffaelea quercivora) is a vector-borne disease transmitted by the flying ambrosia beetle, Platypus quercivorus, and causes mass mortality in the fagaceous species of Japan. The data described in this article are available in Mendeley Data, DOI: 10.17632/xwj98nb39r.1 [1] and include the mortality status of 1089 Quercus crispula and 846 Quercus serrata trees and surrounding forest conditions. The findings using this dataset were published in M. Oguro, S. Imahiro, S. Saito, T. Nakashizuka, Relative importance of multiple scale factors to oak tree mortality due to Japanese oak wilt disease, For. Ecol. Manag. (2015) doi:10.1016/j.foreco.2015.07.016 [2]. PMID- 26543884 TI - Air speed and velocity measurements in a room with a sidewall jet. AB - In mixing ventilation systems, diffusers are often located on side walls and supply quasi-free air jets above the occupied zone. The data presented in this paper shows a new CFD 3D benchmark with two well-defined characteristic zones in the room, i.e., the quasi-free jet zone and the occupied zone. Measurement methods adequate for air velocity and speed measurement were applied: laser Doppler anemometry for the axial velocity component in the jet and low velocity thermal anemometry for the air speed in the occupied zone. Measurements were performed in a physical scale model (1:5) of the room. The kinematic similarity criterion was fulfilled by the equality of the Reynolds numbers in the model and in the prototype. To identify boundary conditions, additional measurements were carried out in the inlet region (as close as possible to the supply opening). The CFD results validation and reporting methods applicable for the benchmark data are proposed in Hurnik et al. (2015) [1]. PMID- 26543885 TI - Gene regulation by long purine tracks in brain related diseases. AB - Purine repeats are randomly distributed in the human genome, however, they show potential role in the transcriptional deregulation of genes. Presence of long tracks of purine repeats in the genome can disturb its integrity and interfere with the cellular behavior by introducing mutations and/or triple stranded structure formation in DNA. Our data revealed interesting finding that a majority of genes carrying purine repeats, of length n>=200, were down regulated and found to be linked with several brain related diseases [1]. The unique feature of the purine repeats found in the present study clearly manifests their significant application in developing therapeutics for neurological diseases. PMID- 26543886 TI - Dataset for the quantitative proteomics analysis of the primary hepatocellular carcinoma with single and multiple lesions. AB - Hepatocellular Carcinoma (HCC) is one of the most common malignant tumor, which is causing the second leading cancer-related death worldwide. The tumor tissues and the adjacent noncancerous tissues obtained from HCC patients with single and multiple lesions were quantified using iTRAQ. A total of 5513 proteins (FDR of 1%) were identified which correspond to roughly 27% of the total liver proteome. And 107 and 330 proteins were dysregulated in HCC tissue with multiple lesions (MC group) and HCC tissue with a single lesion (SC group), compared with their noncancerous tissue (MN and SN group) respectively. Bioinformatics analysis (GO, KEGG and IPA) allowed these data to be organized into distinct categories. The data accompanying the manuscript on this approach (Xing et al., J. Proteomics (2015), http://dx.doi.org/10.1016/j.jprot.2015.08.007[1]) have been deposited to the iProX with identifier IPX00037601. PMID- 26543887 TI - Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome. AB - Synovial fluid is present in all joint cavities, and protects the articular cartilage surfaces in large by lubricating the joint, thus reducing friction. Several studies have described changes in the protein composition of synovial fluid in patients with joint disease. However, the protein concentration, content, and synovial fluid volume change dramatically during active joint diseases and inflammation, and the proteome composition of healthy synovial fluid is incompletely characterized. We performed a normative proteomics analysis of porcine synovial fluid, and report data from optimizing proteomic methods to investigate the proteome of healthy porcine synovial fluid (Bennike et al., 2014 [1]). We included an evaluation of different proteolytic sample preparation techniques, and an analysis of posttranslational modifications with a focus on glycosylation. We used pig (Sus Scrofa) as a model organism, as the porcine immune system is highly similar to human and the pig genome is sequenced. Furthermore, porcine model systems are commonly used large animal models to study several human diseases. In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935. PMID- 26543888 TI - ChIP-Seq analysis of the adult male mouse brain after developmental exposure to arsenic. AB - Exposure to the common environmental contaminant arsenic impacts the epigenetic landscape, including DNA methylation and histone modifications, of several cell types. Developmental arsenic exposure (DAE) increases acetylation and methylation of histone proteins and the protein expression of several chromatin-modifying enzymes in the dentate gyrus (DG) subregion of the adult male mouse brain [26]. To complement and support these data, ChIP-Seq analysis of DNA associated with trimethylation of histone 3 lysine 4 (H3K4me3) derived from the adult male DG after DAE was performed. DAE induced differential H3K4me3 enrichment on genes in pathways associated with cellular development and growth, cell death and survival, and neurological disorders, particularly as they relate to cancer, in the adult male brain. Comparison of H3K4me3 enrichment in controls revealed mechanisms that are potentially lacking in arsenic-exposed animals, including neurotransmission, neuronal growth and development, hormonal regulation, protein synthesis, and cellular homeostasis. New pathways impacted by arsenic include cytoskeleton organization, cell signaling, and potential disruption of immune function and warrant further investigation using this DAE paradigm in the mouse brain. PMID- 26543889 TI - Combining two-dimensional gel electrophoresis and metabolomic data in support of dry-season survival in the two main species of the malarial mosquito Anopheles gambiae. AB - In dry savannahs of West-Africa, the malarial mosquitoes of the Anopheles gambiae sensu stricto complex annually survive the harsh desiccating conditions of the dry season. However, the physiological and biochemical mechanisms underlying how these mosquitoes survive such desiccating conditions are still undefined, and controversial. In this context, we provide the first work examining both proteomic and metabolomic changes in the two molecular forms of A. gambiae s.s (M and S forms) experimentally exposed to the rainy and dry season conditions as they experience in the field. Protein abundances of the mosquitoes were measured using a two-dimensional fluorescence difference gel electrophoresis (2D DIGE) coupled with a matrix-assisted laser desorption/ionisation-time of flight (MALDI TOF) and tandem mass spectrometry (MS) for protein identification. These assays were conducted by Applied Biomics (http://www.appliedbiomics.com, Applied Biomics, Inc. Hayward, CA, USA), and the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD000294. The metabolomic analysis was conducted using both Acquity UPLC((r)) system (for amino acid identification), and a gas chromatography-mass spectrometry platform (for sugars identification). Metabolomic fingerprintings were assessed in the University of Rennes 1, UMR CNRS 6553 EcoBio (France). A detailed interpretation of the obtained data can be found in Hidalgo et al. (2014) [1] (Journal of Insect Physiology (2014)). PMID- 26543890 TI - Data supporting the activation of autophagy genes in the diabetic heart. AB - This data article contains full list of autophagy related genes that are altered in diabetic heart. This article also shows data from in vitro cultured cardiomyocytes that are exposed the high glucose treatment to simulate hyperglycemic state in vitro. The interpretation of these data and further extensive insights into the regulation of SG biogenesis by AMPK can be found in "Type-2 diabetes increases autophagy in the human heart through promotion of Beclin-1 mediated pathway" (Munasinghe et al., in press) [1]. PMID- 26543891 TI - RIME proteomics of estrogen and progesterone receptors in breast cancer. AB - Nuclear receptors play an important role in transcriptional regulation of diverse cellular processes and is also relevant in diseases such as cancer. In breast cancer, the nuclear receptors - estrogen receptor (ER) and progesterone receptor (PR) are classical markers of the disease and are used to classify breast cancer subtypes. Using a recently developed affinity purification MS technique (RIME) [1], we investigate the protein interactors of ER and PR in breast cancer cell lines upon stimulation by the ligands - estrogen and progesterone. The data is deposited at proteomeXchange (PXD002104) and is part of a publication [2] that explains the link between the two nuclear receptors and potential consequences of this in breast cancer. In this manuscript, we describe the methodology used and provide details on experimental procedures, analysis methods and analysis of raw data. The purpose of this article is to enable reproducibility of the data and provide technical recommendations on performing RIME in hormonal contexts. PMID- 26543892 TI - Mitochondrial and nuclear phylogenetic trees and divergence time estimations of Sulawesi endemic Adrianichthyidae. AB - This data article is related to the research article entitled "Origin and intra island diversification of Sulawesi endemic Adrianichthyidae" by Mokodongan and Yamahira [1]. In this data article, we present phylogenetic trees of Sulawesi adrianichthyids separately reconstructed using mitochondrial (cytochrome b: cyt b and NADH dehydrogenase subunit 2: ND2) and nuclear (tyrosinase) sequences. We also present Bayesian chronograms of Sulawesi adrianichthyids separately estimated using a substitution rate for cyt b and for ND2. PMID- 26543893 TI - A structural group-connectome in standard stereotactic (MNI) space. AB - A group connectome of 20 subjects has been normalized into standard stereotactic (MNI) space. Data has been processed using the Gibbs' Tracking approach (Reisert et al., 2011) [11] and normalized into standard space using DARTEL (Ashburner, 2007) [1]. All data has been acquired within the scope of the study A. Horn, D. Ostwald, M. Reisert, F. Blankenburg, The structural-functional connectome and the default mode network of the human brain, NeuroImage 102 (2013) 142-151. http://doi.org/10.1016/j.neuroimage.2013.09.069. The utility of this dataset can be described by the following points: In medical studies in which subject specific dMRI is not available, a standardized connectome may help to gain some canonical insight into white-matter connectivity. The dataset enables scientists who use different modalities (like EEG, MEG etc.) without access to MRI, to combine studies obtained using other methodology with insights from the brain's inner structural formation. The dataset could also extend possible claims made by meta-analyzes/literature-based studies. PMID- 26543895 TI - Convalescing Cluster Configuration Using a Superlative Framework. AB - Competent data mining methods are vital to discover knowledge from databases which are built as a result of enormous growth of data. Various techniques of data mining are applied to obtain knowledge from these databases. Data clustering is one such descriptive data mining technique which guides in partitioning data objects into disjoint segments. K-means algorithm is a versatile algorithm among the various approaches used in data clustering. The algorithm and its diverse adaptation methods suffer certain problems in their performance. To overcome these issues a superlative algorithm has been proposed in this paper to perform data clustering. The specific feature of the proposed algorithm is discretizing the dataset, thereby improving the accuracy of clustering, and also adopting the binary search initialization method to generate cluster centroids. The generated centroids are fed as input to K-means approach which iteratively segments the data objects into respective clusters. The clustered results are measured for accuracy and validity. Experiments conducted by testing the approach on datasets from the UC Irvine Machine Learning Repository evidently show that the accuracy and validity measure is higher than the other two approaches, namely, simple K means and Binary Search method. Thus, the proposed approach proves that discretization process will improve the efficacy of descriptive data mining tasks. PMID- 26543894 TI - Substance P mediates pro-inflammatory cytokine release form mesenteric adipocytes in Inflammatory Bowel Disease patients. AB - BACKGROUND & AIMS: Substance P (SP), neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes and SP binding activates proinflammatory signalling in these cells. We evaluated the expression levels of SP (Tac-1), NK 1R (Tacr-1), and NK-2R (Tacr-2) mRNA in preadipocytes isolated from patients with Inflammatory Bowel Disease (IBD) and examined their responsiveness to SP compared to control human mesenteric preadipocytes. The Aim of our study is to investigate the effects of the neuropeptide SP on cytokine expression in preadipocytes of IBD vs control patients and evaluate the potential effects of these cells on IBD pathophysiology via SP-NK-R interactions. METHODS: Mesenteric fat was collected from control, Ulcerative colitis (UC) and Crohn's disease (CD) patients (n=10-11 per group). Preadipocytes were isolated, expanded in culture and exposed to substance P. Colon biopsies were obtained from control and IBD patients. RESULTS: Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared to controls, while Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared to controls. Disease-dependent responses to SP were also observed between UC and CD preadipocytes. IL-17A mRNA expression and release increased after SP treatment in both CD and UC preadipocytes, while IL-17RA mRNA increased in colon biopsies from IBD patients. CONCLUSIONS: Preadipocyte SP-NK-1R interactions during IBD may participate in IBD pathophysiology. The ability of human preadipocytes to release IL-17A in response to SP together with increased IL-17A receptor in IBD colon opens the possibility of a fat-colonic mucosa inflammatory loop that may be active during IBD. PMID- 26543897 TI - Hybrid Scheduling Model for Independent Grid Tasks. AB - Grid computing facilitates the resource sharing through the administrative domains which are geographically distributed. Scheduling in a distributed heterogeneous environment is intrinsically very hard because of the heterogeneous nature of resource collection. Makespan and tardiness are two different measures of scheduling, and many of the previous researches concentrated much on reduction of makespan, which measures the machine utilization. In this paper, we propose a hybrid scheduling algorithm for scheduling independent grid tasks with the objective of reducing total weighted tardiness of grid tasks. Tardiness is to measure the due date performance, which has a direct impact on cost for executing the jobs. In this paper we propose BG_ATC algorithm which is a combination of best gap (BG) search and Apparent Tardiness Cost (ATC) indexing algorithm. Furthermore, we implemented these two algorithms in two different phases of the scheduling process. In addition to that, the comparison was made on results with various benchmark algorithms and the experimental results show that our algorithm outperforms the benchmark algorithms. PMID- 26543898 TI - Torque Analysis of a Triple Acid-Etched Titanium Implant Surface. AB - The present study aimed to evaluate the removal torque of titanium implants treated with triple acid etching. Twenty-one rats were used in this study. For all animals, the tibia was prepared with a 2 mm drill, and a titanium implant (2 * 4 mm) was inserted after treatment using the subtraction method of triple acid etching. The flaps were sutured. Seven animals were killed 14, 28, and 63 days after implant installation, and the load necessary for removing the implant from the bone was evaluated by using a torque meter. The torque values were as follows: 3.3 +/- 1.7 Ncm (14 days), 2.2 +/- 1.3 Ncm (28 days), and 6.7 +/- 1.4 Ncm (63 days). The torque value at the final healing period (63 days) was statistically significantly different from that at other time points tested (ANOVA, p = 0.0002). This preliminary study revealed that treatment with triple acid etching can create a promising and efficient surface for the process of osseointegration. PMID- 26543896 TI - Apical Extrusion of Debris Produced during Continuous Rotating and Reciprocating Motion. AB - This study aimed to analyse and compare apical extrusion of debris in canals instrumented with systems used in reciprocating and continuous motion. Sixty mandibular premolars were randomly divided into 3 groups (n = 20): the Reciproc (REC), WaveOne (WO), and HyFlex CM (HYF) groups. One Eppendorf tube per tooth was weighed in advance on an analytical balance. The root canals were instrumented according to the manufacturer's instructions, and standardised irrigation with 2.5% sodium hypochlorite was performed to a total volume of 9 mL. After instrumentation, the teeth were removed from the Eppendorf tubes and incubated at 37 degrees C for 15 days to evaporate the liquid. The tubes were weighed again, and the difference between the initial and final weight was calculated to determine the weight of the debris. The data were statistically analysed using the Shapiro-Wilk, Wilcoxon, and Mann-Whitney tests (alpha = 5%). All systems resulted in the apical extrusion of debris. Reciproc produced significantly more debris than WaveOne (p < 0.05), and both systems produced a greater apical extrusion of debris than HyFlex CM (p < 0.001). Cross section and motion influenced the results, despite tip standardization. PMID- 26543899 TI - Optimizing Negotiation Conflict in the Cloud Service Negotiation Framework Using Probabilistic Decision Making Model. AB - Optimization of negotiation conflict in the cloud service negotiation framework is identified as one of the major challenging issues. This negotiation conflict occurs during the bilateral negotiation process between the participants due to the misperception, aggressive behavior, and uncertain preferences and goals about their opponents. Existing research work focuses on the prerequest context of negotiation conflict optimization by grouping similar negotiation pairs using distance, binary, context-dependent, and fuzzy similarity approaches. For some extent, these approaches can maximize the success rate and minimize the communication overhead among the participants. To further optimize the success rate and communication overhead, the proposed research work introduces a novel probabilistic decision making model for optimizing the negotiation conflict in the long-term negotiation context. This decision model formulates the problem of managing different types of negotiation conflict that occurs during negotiation process as a multistage Markov decision problem. At each stage of negotiation process, the proposed decision model generates the heuristic decision based on the past negotiation state information without causing any break-off among the participants. In addition, this heuristic decision using the stochastic decision tree scenario can maximize the revenue among the participants available in the cloud service negotiation framework. PMID- 26543900 TI - Corrigendum to "Validity and Reliability of Farsi Version of Youth Sport Environment Questionnaire". AB - [This corrects the article DOI: 10.1155/2015/985283.]. PMID- 26543901 TI - A Web-Based Intervention for Users of Amphetamine-Type Stimulants: 3-Month Outcomes of a Randomized Controlled Trial. AB - BACKGROUND: Among illicit drugs, the prevalence of amphetamine-type stimulant (ATS) use is second only to cannabis. Currently, there are no approved pharmacotherapies for ATS problems, but some face-to-face psychotherapies are effective. Web-based interventions have proven to be effective for some substance use problems, but none has specifically targeted ATS users. OBJECTIVE: The objective of the study was to evaluate the effectiveness of a Web-based intervention for ATS problems on a free-to-access site compared with a waitlist control group. METHODS: We used a randomized controlled trial design. The primary outcome measure was self-reported ATS use in the past three months assessed using the Alcohol, Smoking, Substance Involvement Screening Test (ASSIST). Other measures included quality of life (EUROHIS score), psychological distress (K-10 score), days out of role, poly-drug use, general help-seeking intentions, actual help-seeking, and "readiness to change". The intervention consisted of three fully automated, self-guided modules based on cognitive behavioral therapy and motivation enhancement. The analysis was an intention-to-treat analysis using generalized estimating equation models, with a group by time interaction as the critical assessment. RESULTS: We randomized 160 people (intervention n=81, control n=79). At three months, 35/81 (43%) intervention and 45/79 (57%) control participants provided follow-up data. In the intervention group, 51/81 (63%) completed at least one module. The only significant group by time interaction was for days out of role. The pre/post change effect sizes showed small changes (range d=0.14 to 0.40) favoring the intervention group for poly-drug use, distress, actual help-seeking, and days out of role. In contrast, the control group was favored by reductions in ATS use, improvements in quality of life, and increases in help-seeking intentions (range d=0.09 to 0.16). CONCLUSIONS: This Web-based intervention for ATS use produced few significant changes in outcome measures. There were moderate, but nonsignificant reductions in poly-drug use, distress, days partially out of role, and increases in help-seeking. However, high levels of participant attrition, plus low levels of engagement with the modules, preclude firm conclusions being drawn on the efficacy of the intervention and emphasize the problems of engaging this group of clients in a fully automated program. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN 12611000947909; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261100094790 (Archived by WebCite at http://www.webcitation.org/6SHTxEnzP). PMID- 26543902 TI - Implementation and Outcomes of a Collaborative Multi-Center Network Aimed at Web Based Cognitive Training - COGWEB Network. AB - BACKGROUND: Cognitive care for the most prevalent neurologic and psychiatric conditions will only improve through the implementation of new sustainable approaches. Innovative cognitive training methodologies and collaborative professional networks are necessary evolutions in the mental health sector. OBJECTIVE: The objective of the study was to describe the implementation process and early outcomes of a nationwide multi-organizational network supported on a Web-based cognitive training system (COGWEB). METHODS: The setting for network implementation was the Portuguese mental health system and the hospital-, academic-, community-based institutions and professionals providing cognitive training. The network started in August 2012, with 16 centers, and was monitored until September 2013 (inclusions were open). After onsite training, all were allowed to use COGWEB in their clinical or research activities. For supervision and maintenance were implemented newsletters, questionnaires, visits and webinars. The following outcomes were prospectively measured: (1) number, (2) type, (3) time to start, and (4) activity state of centers; age, gender, level of education, and medical diagnosis of patients enrolled. RESULTS: The network included 68 professionals from 41 centers, (33/41) 80% clinical, (8/41) 19% nonclinical. A total of 298 patients received cognitive training; 45.3% (n=135) female, mean age 54.4 years (SD 18.7), mean educational level 9.8 years (SD 4.8). The number enrolled each month increased significantly (r=0.6; P=.031). At 12 months, 205 remained on treatment. The major causes of cognitive impairment were: (1) neurodegenerative (115/298, 38.6%), (2) structural brain lesions (63/298, 21.1%), (3) autoimmune (40/298, 13.4%), (4) schizophrenia (30/298, 10.1%), and (5) others (50/298, 16.8%). The comparison of the patient profiles, promoter versus all other clinical centers, showed significant increases in the diversity of causes and spectrums of ages and education. CONCLUSIONS: Over its first year, there was a major increase in the number of new centers and professionals, as well as of the clinical diversity of patients treated. The consolidation of such a national collaborative network represents an innovative step in mental health care evolution. Furthermore, it may contribute to translational processes in the field of cognitive training and reduce disease burden. PMID- 26543903 TI - Assessing the Evidence for e-Resources for Mental Health Self-Management: A Systematic Literature Review. AB - BACKGROUND: In a climate which recognizes mental health as a key health improvement target, but where mental health services are increasingly over stretched, self-management e-resources can play a potentially important role in helping to ensure people get the care and support they need. They have the potential to enable individuals to learn more about, and to exercise active involvement in, their care, and thus we see a growing interest in this area for both research and practice. However, for e-resources to become important adjuncts to clinical care, it is necessary to understand if and how they impact on patients and care outcomes. OBJECTIVE: The objective of this study was to review systematically the research evidence for theory-driven and evidence-based mental health self-management e-resources; and make recommendations about strengthening the future evidence base. METHODS: A comprehensive literature search in MEDLINE, EMBASE, AMED, PsycINFO, Scopus, and Cochrane Library was conducted. No limits to study design were applied. We did not restrict the types of Web-based technologies included, such as websites and mobile applications, so long as they met the study inclusion criteria. A narrative synthesis of data was performed to elaborate both the development and effectiveness of online resources. RESULTS: In total, 2969 abstracts were identified. Of those, 8 papers met the inclusion criteria. Only one randomized controlled trial was identified. The e-resources were aimed at self-management of bipolar disorder, depression, or general mental health problems. Some of the e-resources were intended to be used as prevention aids, whereas others were recovery orientated. CONCLUSIONS: Mental health self management e-resources have the potential to be widely effective, but our review shows it is early days in terms of development of the evidence base for them. To build robust evidence, clear guidelines are needed on the development and reporting of e-resources, so that both developers and researchers maximize the potential of a new, but rapidly evolving area. PMID- 26543905 TI - Patient Smartphone Ownership and Interest in Mobile Apps to Monitor Symptoms of Mental Health Conditions: A Survey in Four Geographically Distinct Psychiatric Clinics. AB - BACKGROUND: Despite growing interest in mobile mental health and utilization of smartphone technology to monitor psychiatric symptoms, there remains a lack of knowledge both regarding patient ownership of smartphones and their interest in using such to monitor their mental health. OBJECTIVE: To provide data on psychiatric outpatients' prevalence of smartphone ownership and interest in using their smartphones to run applications to monitor their mental health. METHODS: We surveyed 320 psychiatric outpatients from four clinics around the United States in order to capture a geographically and socioeconomically diverse patient population. These comprised a state clinic in Massachusetts (n=108), a county clinic in California (n=56), a hybrid public and private clinic in Louisiana (n=50), and a private/university clinic in Wisconsin (n=106). RESULTS: Smartphone ownership and interest in utilizing such to monitor mental health varied by both clinic type and age with overall ownership of 62.5% (200/320), which is slightly higher than the average United States' rate of ownership of 58% in January 2014. Overall patient interest in utilizing smartphones to monitor symptoms was 70.6% (226/320). CONCLUSIONS: These results suggest that psychiatric outpatients are interested in using their smartphones to monitor their mental health and own the smartphones capable of running mental healthcare related mobile applications. PMID- 26543904 TI - Randomized Comparison of Mobile and Web-Tools to Provide Dementia Risk Reduction Education: Use, Engagement and Participant Satisfaction. AB - BACKGROUND: Encouraging middle-aged adults to maintain their physical and cognitive health may have a significant impact on reducing the prevalence of dementia in the future. Mobile phone apps and interactive websites may be one effective way to target this age group. However, to date there has been little research investigating the user experience of dementia risk reduction tools delivered in this way. OBJECTIVE: The aim of this study was to explore participant engagement and evaluations of three different targeted smartphone and Web-based dementia risk reduction tools following a four-week intervention. METHODS: Participants completed a Web-based screening questionnaire to collect eligibility information. Eligible participants were asked to complete a Web-based baseline questionnaire and were then randomly assigned to use one of the three dementia risk reduction tools for a period of four weeks: (1) a mobile phone application; (2) an information-based website; and (3) an interactive website. User evaluations were obtained via a Web-based follow-up questionnaire after completion of the intervention. RESULTS: Of 415 eligible participants, 370 (89.16%) completed the baseline questionnaire and were assigned to an intervention group; 200 (54.05%) completed the post-intervention questionnaire. The average age of participants was 52 years, and 149 (75%) were female. Findings indicated that participants from all three intervention groups reported a generally positive impression of the tools across a range of domains. Participants using the information-based website reported higher ratings of their overall impression of the tool, F2,191=4.12, P=.02; how interesting the information was, F2,189=3.53, P=.03; how helpful the information was, F2,192=4.15, P=.02; and how much they learned, F2,188=3.86, P=.02. Group differences were significant between the mobile phone app and information-based website users, but not between the interactive website users and the other two groups. Additionally, participants using the information-based website reported significantly higher scores on their ratings of the ease of navigation, F2,190=4.20, P=.02, than those using the mobile phone app and the interactive website. There were no significant differences between groups on ratings of ease of understanding the information, F2,188=0.27, P=.76. Most participants from each of the three intervention groups indicated that they intended to keep using the dementia risk reduction eHealth tool. CONCLUSIONS: Overall, results indicated that while participants across all three intervention groups reported a generally positive experience with the targeted dementia risk reduction tools, participants using the information-based website provided a more favorable evaluation across a range of areas than participants using the mobile phone app. Further research is required to investigate whether targeted dementia risk reduction tools, in the form of interactive websites and mobile apps, can be improved to provide benefits above those gained by providing static information alone. PMID- 26543906 TI - Client Perceptions of the Mental Health Engagement Network: A Secondary Analysis of an Intervention Using Smartphones and Desktop Devices for Individuals Experiencing Mood or Psychotic Disorders in Canada. AB - BACKGROUND: The use of innovative technologies in mental health care has the potential to improve system efficiency, enhance quality of care, and increase patient engagement. The Mental Health Engagement Network (MHEN) project developed, delivered, and evaluated an interactive Web-based personal health record, the Lawson SMART Record (LSR), to assist mental health clients in managing their care and connecting with their care providers. This paper presents a secondary analysis of data collected in the MHEN project regarding clients' perceptions of technology and the use of these technologies in their care. OBJECTIVE: We aimed to answer six questions: (1) What is the level of comfort with technology within a sample of individuals experiencing mood or psychotic disorders? (2) How easy to use and helpful are the MHEN technologies from the perspective of individuals experiencing a mental illness? (3) Are there differences in how helpful or useful individuals find the smartphone compared to the LSR? (4) Are there specific functions of MHEN technologies (eg, reminders for medications or appointments) that are more valued than others? (5) What are the other ways that individuals are using MHEN technologies in their daily lives? (6) How likely are individuals to be able to retain and maintain their smartphone? METHODS: Mental health clients aged 18-80 (N=400) and diagnosed with a mood or psychotic disorder were provided with a smartphone (iPhone 4S) and participating care providers (n=52) were provided with a tablet (iPad) in order to access and engage with the LSR. A delayed implementation design with mixed methods was used. Survey and interview data were collected over the course of 18 months through semistructured interviews conducted by experienced research assistants every 6 months post-implementation of the intervention. Paired t tests were used to determine differences between 6 and 12-month data for perceptions of the MHEN technologies. A paired t test was used to examine whether differences existed between perceptions of the smartphone and the LSR at 12 months post implementation. RESULTS: Due to dropout or loss of contact, 394 out of 400 individuals completed the study. At the end of the study, 52 devices were lost or unusable. Prior to the intervention, participants reported being comfortable using technology. Perceptions of the MHEN technologies and their functions were generally positive. Positive perceptions of the smartphone increased over time (P=.002), while positive perceptions of the LSR decreased over time (P<.001). CONCLUSIONS: Quantitative and qualitative findings from this analysis demonstrated that these technologies positively impacted the lives of individuals experiencing severe mental illnesses and dispeled some of the myths regarding retention of technology among marginalized populations. This secondary analysis supported the acceptability of using mental health technologies within this population and provided considerations for future development. TRIAL REGISTRATION: ClinicalTrials.gov NCT01473550; http://clinicaltrials.gov/show/NCT01473550 (Archived by WebCite at http://www.webcitation.org/6SLNcoKb8). PMID- 26543907 TI - Mental Health Mobile Apps: From Infusion to Diffusion in the Mental Health Social System. AB - The roles of mental health educators and professionals in the diffusion of mental health mobile apps are addressed in this viewpoint article. Mental health mobile apps are emerging technologies that fit under the broad heading of mobile health (mHealth). mHealth, encompassed within electronic health (eHealth), reflects the use of mobile devices for the practice of public health. Well-designed mental health mobile apps that present content in interactive, engaging, and stimulating ways can promote cognitive learning, personal growth, and mental health enhancement. As key influencers in the mental health social system, counselor educators and professional associations may either help or hinder diffusion of beneficial mHealth technologies. As mental health mobile apps move towards ubiquity, research will continue to be conducted. The studies published thus far, combined with the potential of mental health mobile apps for learning and personal growth, offer enough evidence to compel mental health professionals to infuse these technologies into education and practice. Counselor educators and professional associations must use their influential leadership roles to train students and practitioners in how to research, evaluate, and integrate mental health mobile apps into practice. The objectives of this article are to (1) increase awareness of mHealth and mental health mobile apps, (2) demonstrate the potential for continued growth in mental health mobile apps based on technology use and acceptance theory, mHealth organizational initiatives, and evidence about how humans learn, (3) discuss evidence-based benefits of mental health mobile apps, (4) examine the current state of mHealth diffusion in the mental health profession, and (5) offer solutions for impelling innovation diffusion by infusing mental health mobile apps into education, training, and clinical settings. This discussion has implications for counselor educators, mental health practitioners, associations, continuing education providers, and app developers. PMID- 26543908 TI - A Virtual Mental Health Clinic for University Students: A Qualitative Study of End-User Service Needs and Priorities. AB - BACKGROUND: Help seeking for mental health problems among university students is low, and Internet-based interventions such as virtual clinics have the potential to provide private, streamlined, and high quality care to this vulnerable group. OBJECTIVE: The objective of this study was to conduct focus groups with university students to obtain input on potential functions and features of a university-specific virtual clinic for mental health. METHODS: Participants were 19 undergraduate students from an Australian university between 19 and 24 years of age. Focus group discussion was structured by questions that addressed the following topics: (1) the utility and acceptability of a virtual mental health clinic for students, and (2) potential features of a virtual mental health clinic. RESULTS: Participants viewed the concept of a virtual clinic for university students favorably, despite expressing concerns about privacy of personal information. Participants expressed a desire to connect with professionals through the virtual clinic, for the clinic to provide information tailored to issues faced by students, and for the clinic to enable peer-to-peer interaction. CONCLUSIONS: Overall, results of the study suggest the potential for virtual clinics to play a positive role in providing students with access to mental health support. PMID- 26543909 TI - Breaking Open the Black Box: Isolating the Most Potent Features of a Web and Mobile Phone-Based Intervention for Depression, Anxiety, and Stress. AB - BACKGROUND: Internet-delivered mental health (eMental Health) interventions produce treatment effects similar to those observed in face-to-face treatment. However, there is a large degree of variation in treatment effects observed from program to program, and eMental Health interventions remain somewhat of a black box in terms of the mechanisms by which they exert their therapeutic benefit. Trials of eMental Health interventions typically use large sample sizes and therefore provide an ideal context within which to systematically investigate the therapeutic benefit of specific program features. Furthermore, the growth and impact of mobile phone technology within eMental Health interventions provides an opportunity to examine associations between symptom improvement and the use of program features delivered across computer and mobile phone platforms. OBJECTIVE: The objective of this study was to identify the patterns of program usage associated with treatment outcome in a randomized controlled trial (RCT) of a fully automated, mobile phone- and Web-based self-help program, "myCompass", for individuals with mild-to-moderate symptoms of depression, anxiety, and/or stress. The core features of the program include interactive psychotherapy modules, a symptom tracking feature, short motivational messages, symptom tracking reminders, and a diary, with many of these features accessible via both computer and mobile phone. METHODS: Patterns of program usage were recorded for 231 participants with mild-to-moderate depression, anxiety, and/or stress, and who were randomly allocated to receive access to myCompass for seven weeks during the RCT. Depression, anxiety, stress, and functional impairment were examined at baseline and at eight weeks. RESULTS: Log data indicated that the most commonly used components were the short motivational messages (used by 68.4%, 158/231 of participants) and the symptom tracking feature (used by 61.5%, 142/231 of participants). Further, after controlling for baseline symptom severity, increased use of these alert features was associated with significant improvements in anxiety and functional impairment. Associations between use of symptom tracking reminders and improved treatment outcome remained significant after controlling for frequency of symptom tracking. Although correlations were not statistically significant, reminders received via SMS (ie, text message) were more strongly associated with symptom reduction than were reminders received via email. CONCLUSIONS: These findings indicate that alerts may be an especially potent component of eMental Health interventions, both via their association with enhanced program usage, as well as independently. Although there was evidence of a stronger association between symptom improvement and use of alerts via the mobile phone platform, the degree of overlap between use of email and SMS alerts may have precluded identification of alert delivery modalities that were most strongly associated with symptom reduction. Future research using random assignment to computer and mobile delivery is needed to fully determine the most ideal platform for delivery of this and other features of online interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12610000625077; http://www.anzctr.org.au/TrialSearch.aspx? (Archived by WebCite http://www.webcitation.org/6WPqHK0mQ). PMID- 26543910 TI - Feasibility and Perception of Using Text Messages as an Adjunct Therapy for Low Income, Minority Mothers With Postpartum Depression. AB - BACKGROUND: Postpartum depression (PPD) is the most common medical problem among new mothers that can have a negative impact on infant health. Traditional treatments are often difficult for low-income mothers to complete, particularly given the numerous barriers families face. OBJECTIVE: Among low-income, primarily racial, and ethnic minority mothers with postpartum depression, our aim was to evaluate (1) the feasibility of sending supportive text messages, and (2) the perception of receiving private, supportive text messages for postpartum depression. METHODS: Mothers found to be at risk for postpartum depression received supportive text messages four times weekly for 6 months in addition to receiving access to traditional counseling services based within an academic pediatric office. Feasibility was evaluated along with cellular and text messaging use, access, and perception of the message protocol. Perception of the message protocol was evaluated at study completion via a Likert scale questionnaire and open-ended qualitative survey. RESULTS: In total, 4158/4790 (86.81%) text messages were successfully delivered to 54 mothers over a 6-month period at a low cost (US $777.60). Among the 96 scripted messages, 37 unique messages (38.54%) allowed for a response. Of all sent messages that allowed for responses, 7.30% (118/1616) were responded to, and 66.1% of those responses requested a call back; 46% (25/54) of mothers responded at least once to a text message. Mothers felt that messages were easily received and read (25/28, 89%) and relevant to them personally (23/28, 82%). Most shared texts with others (21/28, 75%). CONCLUSIONS: Text messaging is feasible, well-accepted, and may serve as a simple, inexpensive adjunct therapy well-suited to cross socioeconomic boundaries and provide private support for at-risk mothers suffering from postpartum depression. PMID- 26543911 TI - Evaluation of an Online Campaign for Promoting Help-Seeking Attitudes for Depression Using a Facebook Advertisement: An Online Randomized Controlled Experiment. AB - BACKGROUND: A depression-awareness campaign delivered through the Internet has been recommended as a public health approach that would enhance mental health literacy and encourage help-seeking attitudes. However, the outcomes of such a campaign remain understudied. OBJECTIVE: The main aim of this study was to evaluate the effectiveness of an online depression awareness campaign, which was informed by the theory of planned behavior, to encourage help-seeking attitudes for depression and to enhance mental health literacy in Hong Kong. The second aim was to examine click-through behaviors by varying the affective facial expressions of people in the Facebook advertisements. METHODS: Potential participants were recruited through Facebook advertisements, using either a happy or sad face illustration. Volunteer participants registered for the study by clicking on the advertisement and were invited to leave their personal email addresses to receive educational content about depression. The participants were randomly assigned into two groups (campaign or control), and over a four consecutive week period, received either the campaign material or official information developed by the Hospital Authority in Hong Kong. Pretests and posttests were conducted before and after the campaign to measure the differences in help-seeking attitudes and mental health literacy among the campaign and control groups. RESULTS: Of the 199 participants that registered and completed the pretest, 116 (55 campaign and 62 control) completed the campaign and the posttest. At the posttest, we found no significant changes in help-seeking attitudes between the campaign and control groups, but the campaign group participants demonstrated a statistically significant improvement in mental health literacy (P=.031) and a higher willingness to access additional information (P<.001) than the control group. Moreover, the happy face Facebook advertisement attracted more click-throughs by users into the website than did the sad face advertisement (P=.03). CONCLUSIONS: The present study provides evidence that an online campaign can enhance people's mental health literacy. It also demonstrates the practicality and effectiveness of an online depression awareness campaign using a Facebook-based recruitment strategy and distribution of educational materials through emails. It is important for future studies to take advantage of the popularity of online social media and conduct evaluative research on mental health promotion campaigns. PMID- 26543912 TI - Clinical Practice Models for the Use of E-Mental Health Resources in Primary Health Care by Health Professionals and Peer Workers: A Conceptual Framework. AB - BACKGROUND: Research into e-mental health technologies has developed rapidly in the last 15 years. Applications such as Internet-delivered cognitive behavioral therapy interventions have accumulated considerable evidence of efficacy and some evidence of effectiveness. These programs have achieved similar outcomes to face to-face therapy, while requiring much less clinician time. There is now burgeoning interest in integrating e-mental health resources with the broader mental health delivery system, particularly in primary care. The Australian government has supported the development and deployment of e-mental health resources, including websites that provide information, peer-to-peer support, automated self-help, and guided interventions. An ambitious national project has been commissioned to promote key resources to clinicians, to provide training in their use, and to evaluate the impact of promotion and training upon clinical practice. Previous initiatives have trained clinicians to use a single e-mental health program or a suite of related programs. In contrast, the current initiative will support community-based service providers to access a diverse array of resources developed and provided by many different groups. OBJECTIVE: The objective of this paper was to develop a conceptual framework to support the use of e-mental health resources in routine primary health care. In particular, models of clinical practice are required to guide the use of the resources by diverse service providers and to inform professional training, promotional, and evaluation activities. METHODS: Information about service providers' use of e mental health resources was synthesized from a nonsystematic overview of published literature and the authors' experience of training primary care service providers. RESULTS: Five emerging clinical practice models are proposed: (1) promotion; (2) case management; (3) coaching; (4) symptom-focused treatment; and (5) comprehensive therapy. We also consider the service provider skills required for each model and the ways that e-mental health resources might be used by general practice doctors and nurses, pharmacists, psychologists, social workers, occupational therapists, counselors, and peer workers. CONCLUSIONS: The models proposed in the current paper provide a conceptual framework for policy-makers, researchers and clinicians interested in integrating e-mental health resources into primary care. Research is needed to establish the safety and effectiveness of the models in routine care and the best ways to support their implementation. PMID- 26543913 TI - mHealth in the Wild: Using Novel Data to Examine the Reach, Use, and Impact of PTSD Coach. AB - BACKGROUND: A majority of Americans (58%) now use smartphones, making it possible for mobile mental health apps to reach large numbers of those who are living with untreated, or under-treated, mental health symptoms. Although early trials suggest positive effects for mobile health (mHealth) interventions, little is known about the potential public health impact of mobile mental health apps. OBJECTIVE: The purpose of this study was to characterize reach, use, and impact of "PTSD Coach", a free, broadly disseminated mental health app for managing posttraumatic stress disorder (PTSD) symptoms. METHODS: Using a mixed-methods approach, aggregate mobile analytics data from 153,834 downloads of PTSD Coach were analyzed in conjunction with 156 user reviews. RESULTS: Over 60% of users engaged with PTSD Coach on multiple occasions (mean=6.3 sessions). User reviews reflected gratitude for the availability of the app and being able to use the app specifically during moments of need. PTSD Coach users reported relatively high levels of trauma symptoms (mean PTSD Checklist Score=57.2, SD=15.7). For users who chose to use a symptom management tool, distress declined significantly for both first-time users (mean=1.6 points, SD=2.6 on the 10-point distress thermometer) and return-visit users (mean=2.0, SD=2.3). Analysis of app session data identified common points of attrition, with only 80% of first-time users reaching the app's home screen and 37% accessing one of the app's primary content areas. CONCLUSIONS: These findings suggest that PTSD Coach has achieved substantial and sustained reach in the population, is being used as intended, and has been favorably received. PTSD Coach is a unique platform for the delivery of mobile mental health education and treatment, and continuing evaluation and improvement of the app could further strengthen its public health impact. PMID- 26543914 TI - Utilizing a Personal Smartphone Custom App to Assess the Patient Health Questionnaire-9 (PHQ-9) Depressive Symptoms in Patients With Major Depressive Disorder. AB - BACKGROUND: Accurate reporting of patient symptoms is critical for diagnosis and therapeutic monitoring in psychiatry. Smartphones offer an accessible, low-cost means to collect patient symptoms in real time and aid in care. OBJECTIVE: To investigate adherence among psychiatric outpatients diagnosed with major depressive disorder in utilizing their personal smartphones to run a custom app to monitor Patient Health Questionnaire-9 (PHQ-9) depression symptoms, as well as to examine the correlation of these scores to traditionally administered (paper and-pencil) PHQ-9 scores. METHODS: A total of 13 patients with major depressive disorder, referred by their clinicians, received standard outpatient treatment and, in addition, utilized their personal smartphones to run the study app to monitor their symptoms. Subjects downloaded and used the Mindful Moods app on their personal smartphone to complete up to three survey sessions per day, during which a randomized subset of PHQ-9 symptoms of major depressive disorder were assessed on a Likert scale. The study lasted 29 or 30 days without additional follow-up. Outcome measures included adherence, measured by the percentage of completed survey sessions, and estimates of daily PHQ-9 scores collected from the smartphone app, as well as from the traditionally administered PHQ-9. RESULTS: Overall adherence was 77.78% (903/1161) and varied with time of day. PHQ-9 estimates collected from the app strongly correlated (r=.84) with traditionally administered PHQ-9 scores, but app-collected scores were 3.02 (SD 2.25) points higher on average. More subjects reported suicidal ideation using the app than they did on the traditionally administered PHQ-9. CONCLUSIONS: Patients with major depressive disorder are able to utilize an app on their personal smartphones to self-assess their symptoms of major depressive disorder with high levels of adherence. These app-collected results correlate with the traditionally administered PHQ-9. Scores recorded from the app may potentially be more sensitive and better able to capture suicidality than the traditional PHQ-9. PMID- 26543915 TI - Privacy Issues in the Development of a Virtual Mental Health Clinic for University Students: A Qualitative Study. AB - BACKGROUND: There is a growing need to develop online services for university students with the capacity to complement existing services and efficiently address student mental health problems. Previous research examining the development and acceptability of online interventions has revealed that issues such as privacy critically impact user willingness to engage with these services. OBJECTIVE: To explore university student perspectives on privacy issues related to using an online mental health service within the context of the development of an online, university-based virtual mental health clinic. METHODS: There were two stages of data collection. The first stage consisted of four 1.5-hour focus groups conducted with university students (n=19; 10 female, 9 male, mean age = 21.6 years) to determine their ideas about the virtual clinic including privacy issues. The second stage comprised three 1-hour prototype testing sessions conducted with university students (n=6; 3 male, 3 female, mean age = 21.2 years) using participatory design methods to develop and refine a service model for the virtual clinic and determine student views on privacy within this context. RESULTS: The students raised a number of issues related to privacy in relation to the development of the university virtual clinic. Major topics included the types of personal information they would be willing to provide (minimal information and optional mental health data), concern about potential access to their personal data by the university, the perceived stigma associated with registering for the service, and privacy and anonymity concerns related to online forums contained within the virtual clinic. CONCLUSIONS: Students would be more comfortable providing personal information and engaging with the virtual clinic if they trust the privacy and security of the service. Implications of this study include building the clinic in a flexible way to accommodate user preferences. PMID- 26543916 TI - Integrating Health Behavior Theory and Design Elements in Serious Games. AB - BACKGROUND: Internet interventions for improving health and well-being have the potential to reach many people and fill gaps in service provision. Serious gaming interfaces provide opportunities to optimize user adherence and impact. Health interventions based in theory and evidence and tailored to psychological constructs have been found to be more effective to promote behavior change. Defining the design elements which engage users and help them to meet their goals can contribute to better informed serious games. OBJECTIVE: To elucidate design elements important in SPARX, a serious game for adolescents with depression, from a user-centered perspective. METHODS: We proposed a model based on an established theory of health behavior change and practical features of serious game design to organize ideas and rationale. We analyzed data from 5 studies comprising a total of 22 focus groups and 66 semistructured interviews conducted with youth and families in New Zealand and Australia who had viewed or used SPARX. User perceptions of the game were applied to this framework. RESULTS: A coherent framework was established using the three constructs of self-determination theory (SDT), autonomy, competence, and relatedness, to organize user perceptions and design elements within four areas important in design: computer game, accessibility, working alliance, and learning in immersion. User perceptions mapped well to the framework, which may assist developers in understanding the context of user needs. By mapping these elements against the constructs of SDT, we were able to propose a sound theoretical base for the model. CONCLUSIONS: This study's method allowed for the articulation of design elements in a serious game from a user-centered perspective within a coherent overarching framework. The framework can be used to deliberately incorporate serious game design elements that support a user's sense of autonomy, competence, and relatedness, key constructs which have been found to mediate motivation at all stages of the change process. The resulting model introduces promising avenues for future exploration. Involving users in program design remains an imperative if serious games are to be fit for purpose. PMID- 26543917 TI - Factor Structure of the Internet Addiction Test in Online Gamers and Poker Players. AB - BACKGROUND: The Internet Addiction Test (IAT) is the most widely used questionnaire to screen for problematic Internet use. Nevertheless, its factorial structure is still debated, which complicates comparisons among existing studies. Most previous studies were performed with students or community samples despite the probability of there being more problematic Internet use among users of specific applications, such as online gaming or gambling. OBJECTIVE: To assess the factorial structure of a modified version of the IAT that addresses specific applications, such as video games and online poker. METHODS: Two adult samples one sample of Internet gamers (n=920) and one sample of online poker players (n=214)-were recruited and completed an online version of the modified IAT. Both samples were split into two subsamples. Two principal component analyses (PCAs) followed by two confirmatory factor analyses (CFAs) were run separately. RESULTS: The results of principal component analysis indicated that a one-factor model fit the data well across both samples. In consideration of the weakness of some IAT items, a 17-item modified version of the IAT was proposed. CONCLUSIONS: This study assessed, for the first time, the factorial structure of a modified version of an Internet-administered IAT on a sample of Internet gamers and a sample of online poker players. The scale seems appropriate for the assessment of such online behaviors. Further studies on the modified 17-item IAT version are needed. PMID- 26543918 TI - Effectiveness of Computer-Assisted Therapy for Substance Dependence Using Breaking Free Online: Subgroup Analyses of a Heterogeneous Sample of Service Users. AB - BACKGROUND: Substance misuse services within the United Kingdom have traditionally been oriented to opiate and crack users, and attended predominantly by male service users. Groups who do not fit this demographic, such as women or those whose primary drug of choice is neither heroin nor crack, have tended to be underrepresented in services. In addition, there can be stigma associated with traditional opiate and crack-centric services. Therefore, the computerized treatment and recovery program, Breaking Free Online (BFO), was developed to enable service users to access confidential support for dependence on a wide range of substances. BFO is delivered as computer-assisted therapy (CAT), or, where appropriate, used as self-help. OBJECTIVE: The aim of this study was to report psychometric outcomes data from 393 service users accessing online support for substance misuse via BFO. METHODS: Following initial referral to substance misuse services, all participants were supported in setting up a BFO login by a practitioner or peer mentor, and, where required, assisted as they completed an online baseline assessment battery contained within the BFO program. Following a period of engagement with BFO, all participants completed the same battery of assessments, and changes in the scores on these assessments were examined. RESULTS: Significant improvements were found across the 393 service users in several areas of psychosocial functioning, including quality of life, severity of alcohol and drug dependence, depression, and anxiety (P=<.001 across all aspects of functioning). Additionally, significant improvements were found within specific subgroups of participants, including females (P=.001-<.001), males (P=.004-<.001), service users reporting alcohol dependence (P=.002-<.001), opiate and crack dependence (P=.014-<.001), and those seeking support for other substances that may be less well represented in the substance misuse sector (P=.001-<.001). CONCLUSIONS: Data from this study indicates that BFO is an effective clinical treatment for a wide range of individuals requiring support for substance misuse. Further work is currently underway to examine more closely the clinical effectiveness of the program. PMID- 26543919 TI - An Online, Moderated Peer-to-Peer Support Bulletin Board for Depression: User Perceived Advantages and Disadvantages. AB - BACKGROUND: Online, peer-to-peer support groups for depression are common on the World Wide Web and there is some evidence of their effectiveness. However, little is known about the mechanisms by which Internet support groups (ISGs) might work. OBJECTIVE: This study aimed to investigate consumer perceptions of the benefits and disadvantages of online peer-to-peer support by undertaking a content analysis of the spontaneous posts on BlueBoard, a well-established, moderated, online depression bulletin board. METHODS: The research set comprised all posts on the board (n=3645) for each of 3 months selected at 4 monthly intervals over 2011. The data were analyzed using content analysis and multiple coders. RESULTS: A total of 586 relevant posts were identified, 453 (77.3%) reporting advantages and 133 (22.7%) reporting disadvantages. Positive personal change (335/453, 74.0%) and valued social interactions and support (296/453, 65.3%) emerged as perceived advantages. Other identified benefits were valued opportunities to disclose/express feelings or views (29/453, 6.4%) and advantages of the BlueBoard environment (45/453, 9.9%). Disadvantages were negative personal change (50/133, 37.6%), perceived disadvantages of board rules/moderation (42/133, 31.6%), unhelpful social interactions/contact with other members (40/133, 30.1%), and technical obstacles to using the board (14/133, 10.5%). CONCLUSIONS: Consumers value the opportunity to participate in an online mutual support group for mental health concerns. Further research is required to better understand how and if these perceived advantages translate into positive outcomes for consumers, and whether the perceived disadvantages of such boards can be addressed without compromising the safety and positive outcomes of the board. PMID- 26543920 TI - Adjustment Disorders Are Uniquely Suited for eHealth Interventions: Concept and Case Study. AB - BACKGROUND: Adjustment disorders (also known as mental distress in response to a stressor) are among the most frequently diagnosed mental disorders in psychiatry and clinical psychology worldwide. They are also commonly diagnosed in clients engaging in deliberate self-harm and in those consulting general practitioners. However, their reputation in research-oriented mental health remains weak since they are largely underresearched. This may change when the International Statistical Classification of Diseases-11 (ICD-11) by the World Health Organization is introduced, including a new conceptualization of adjustment disorders as a stress-response disorder with positively defined core symptoms. OBJECTIVE: This paper provides an overview of evidence-based interventions for adjustment disorders. METHODS: We reviewed the new ICD-11 concept of adjustment disorder and discuss the the rationale and case study of an unguided self-help protocol for burglary victims with adjustment disorder, and its possible implementation as an eHealth intervention. RESULTS: Overall, the treatment with the self-help manual reduced symptoms of adjustment disorder, namely preoccupation and failure to adapt, as well as symptoms of depression, anxiety, and stress. CONCLUSIONS: E-mental health options are considered uniquely suited for offering early intervention after the experiences of stressful life events that potentially trigger adjustment disorders. PMID- 26543921 TI - Identifying Chinese Microblog Users With High Suicide Probability Using Internet Based Profile and Linguistic Features: Classification Model. AB - BACKGROUND: Traditional offline assessment of suicide probability is time consuming and difficult in convincing at-risk individuals to participate. Identifying individuals with high suicide probability through online social media has an advantage in its efficiency and potential to reach out to hidden individuals, yet little research has been focused on this specific field. OBJECTIVE: The objective of this study was to apply two classification models, Simple Logistic Regression (SLR) and Random Forest (RF), to examine the feasibility and effectiveness of identifying high suicide possibility microblog users in China through profile and linguistic features extracted from Internet based data. METHODS: There were nine hundred and nine Chinese microblog users that completed an Internet survey, and those scoring one SD above the mean of the total Suicide Probability Scale (SPS) score, as well as one SD above the mean in each of the four subscale scores in the participant sample were labeled as high risk individuals, respectively. Profile and linguistic features were fed into two machine learning algorithms (SLR and RF) to train the model that aims to identify high-risk individuals in general suicide probability and in its four dimensions. Models were trained and then tested by 5-fold cross validation; in which both training set and test set were generated under the stratified random sampling rule from the whole sample. There were three classic performance metrics (Precision, Recall, F1 measure) and a specifically defined metric "Screening Efficiency" that were adopted to evaluate model effectiveness. RESULTS: Classification performance was generally matched between SLR and RF. Given the best performance of the classification models, we were able to retrieve over 70% of the labeled high-risk individuals in overall suicide probability as well as in the four dimensions. Screening Efficiency of most models varied from 1/4 to 1/2. Precision of the models was generally below 30%. CONCLUSIONS: Individuals in China with high suicide probability are recognizable by profile and text-based information from microblogs. Although there is still much space to improve the performance of classification models in the future, this study may shed light on preliminary screening of risky individuals via machine learning algorithms, which can work side-by-side with expert scrutiny to increase efficiency in large-scale surveillance of suicide probability from online social media. PMID- 26543922 TI - Preferences of Young Adults With First-Episode Psychosis for Receiving Specialized Mental Health Services Using Technology: A Survey Study. AB - BACKGROUND: Despite the potential and interest of using technology for delivering specialized psychiatric services to young adults, surprisingly limited attention has been paid to systematically assess their perspectives in this regard. For example, limited knowledge exists on the extent to which young people receiving specialized services for a first-episode psychosis (FEP) are receptive to using new technologies as part of mental health care, and to which types of technology enabled mental health interventions they are amenable to. OBJECTIVE: The purpose of this study is to assess the interest of young adults with FEP in using technology to receive mental health information, services, and supports. METHODS: This study uses a cross-sectional, descriptive survey design. A convenience sample of 67 participants between the ages of 18 and 35 were recruited from two specialized early intervention programs for psychosis. Interviewer-administered surveys were conducted between December 2013 and October 2014. Descriptive statistics are reported. RESULTS: Among the 67 respondents who completed the survey, the majority (85%, 57/67) agreed or strongly agreed with YouTube as a platform for mental health-related services and supports. The top five technology enabled services that participants were amenable to were (1) information on medication (96%, 64/67); (2) information on education, career, and employment (93%, 62/67); (3) decision-making tools pertaining to treatment and recovery (93%, 62/67); (4) reminders for appointments via text messaging (93%, 62/67); and (5) information about mental health, psychosis, and recovery in general (91%, 61/67). The top self-reported barriers to seeking mental health information online were lack of knowledge on how to perform an Internet search (31%, 21/67) and the way information is presented online (27%, 18/67). Two thirds (67%; 45/67) reported being comfortable in online settings, and almost half (48%; 32/67) reported a preference for mixed formats when viewing mental health information online (eg, text, video, visual graphics). CONCLUSIONS: Young people diagnosed with FEP express interest in using the Internet, social media, and mobile technologies for receiving mental health-related services. Increasing the awareness of young people in relation to various forms of technology-enabled mental health care warrants further attention. A consideration for future research is to obtain more in-depth knowledge on young people's perspectives, which can help improve the design, development, and implementation of integrated technological health innovations within the delivery of specialized mental health care. PMID- 26543923 TI - Online Peer-to-Peer Support for Young People With Mental Health Problems: A Systematic Review. AB - BACKGROUND: Adolescence and early adulthood are critical periods for the development of mental disorders. Online peer-to-peer communication is popular among young people and may improve mental health by providing social support. Previous systematic reviews have targeted Internet support groups for adults with mental health problems, including depression. However, there have been no systematic reviews examining the effectiveness of online peer-to-peer support in improving the mental health of adolescents and young adults. OBJECTIVE: The aim of this review was to systematically identify available evidence for the effectiveness of online peer-to peer support for young people with mental health problems. METHODS: The PubMed, PsycInfo, and Cochrane databases were searched using keywords and Medical Subject Headings (MeSH) terms. Retrieved abstracts (n=3934) were double screened and coded. Studies were included if they (1) investigated an online peer-to-peer interaction, (2) the interaction discussed topics related to mental health, (3) the age range of the sample was between 12 to 25 years, and (4) the study evaluated the effectiveness of the peer-to-peer interaction. RESULTS: Six studies satisfied the inclusion criteria for the current review. The studies targeted a range of mental health problems including depression and anxiety (n=2), general psychological problems (n=1), eating disorders (n=1), and substance use (tobacco) (n=2). The majority of studies investigated Internet support groups (n=4), and the remaining studies focused on virtual reality chat sessions (n=2). In almost all studies (n=5), the peer support intervention was moderated by health professionals, researchers or consumers. Studies employed a range of study designs including randomized controlled trials (n=3), pre-post studies (n=2) and one randomized trial. Overall, two of the randomized controlled trials were associated with a significant positive outcome in comparison to the control group at post intervention. In the remaining four studies, peer-to-peer support was not found to be effective. CONCLUSIONS: This systematic review identified an overall lack of high-quality studies examining online peer-to-peer support for young people. Given that peer support is frequently used as an adjunct to Internet interventions for a variety of mental health conditions, there is an urgent need to determine the effectiveness of peer support alone as an active intervention. PMID- 26543924 TI - Word Recall: Cognitive Performance Within Internet Surveys. AB - BACKGROUND: The use of online surveys for data collection has increased exponentially, yet it is often unclear whether interview-based cognitive assessments (such as face-to-face or telephonic word recall tasks) can be adapted for use in application-based research settings. OBJECTIVE: The objective of the current study was to compare and characterize the results of online word recall tasks to those of the Health and Retirement Study (HRS) and determine the feasibility and reliability of incorporating word recall tasks into application based cognitive assessments. METHODS: The results of the online immediate and delayed word recall assessment, included within the Women's Health and Valuation (WHV) study, were compared to the results of the immediate and delayed recall tasks of Waves 5-11 (2000-2012) of the HRS. RESULTS: Performance on the WHV immediate and delayed tasks demonstrated strong concordance with performance on the HRS tasks (rhoc=.79, 95% CI 0.67-0.91), despite significant differences between study populations (P<.001) and study design. Sociodemographic characteristics and self-reported memory demonstrated similar relationships with performance on both the HRS and WHV tasks. CONCLUSIONS: The key finding of this study is that the HRS word recall tasks performed similarly when used as an online cognitive assessment in the WHV. Online administration of cognitive tests, which has the potential to significantly reduce participant and administrative burden, should be considered in future research studies and health assessments. PMID- 26543925 TI - How Patients Contribute to an Online Psychoeducation Forum for Bipolar Disorder: A Virtual Participant Observation Study. AB - BACKGROUND: In a recent exploratory randomized controlled trial, an online psychoeducation intervention for bipolar disorder has been found to be feasible and acceptable to patients and may positively impact on their self-management behaviors and quality of life. OBJECTIVE: The objective of the study was to investigate how these patients contribute to an online forum for bipolar disorder and the issues relevant for them. METHODS: Participants in the intervention arm of the Bipolar Interactive PsychoEDucation ("BIPED") trial were invited to contribute to the Beating Bipolar forum alongside receiving interactive online psychoeducation modules. Within this virtual participant observation study, forum posts were analyzed using thematic analysis, incorporating aspects of discourse analysis. RESULTS: The key themes which arose from the forum posts included: medication, employment, stigma, social support, coping strategies, insight and acceptance, the life chart, and negative experiences of health care. Participants frequently provided personal narratives relating to their history of bipolar disorder, life experiences, and backgrounds, which often contained emotive language and humor. They regularly sought and offered advice, and expressed encouragement and empathy. The forum would have benefitted from more users to offer a greater support network with more diverse views and experiences. CONCLUSIONS: Online forums are inexpensive to provide and may offer peer support and the opportunity for patients to share their experiences and explore issues related to their illness anonymously. Future research should focus on how to enhance patient engagement with online health care forums. TRIAL REGISTRATION: ISRCTN81375447; http://www.isrctn.com/ISRCTN81375447 (Archived by WebCite at http://www.webcitation.org/6YzWtHUqu). PMID- 26543926 TI - cStress: Towards a Gold Standard for Continuous Stress Assessment in the Mobile Environment. AB - Recent advances in mobile health have produced several new models for inferring stress from wearable sensors. But, the lack of a gold standard is a major hurdle in making clinical use of continuous stress measurements derived from wearable sensors. In this paper, we present a stress model (called cStress) that has been carefully developed with attention to every step of computational modeling including data collection, screening, cleaning, filtering, feature computation, normalization, and model training. More importantly, cStress was trained using data collected from a rigorous lab study with 21 participants and validated on two independently collected data sets - in a lab study on 26 participants and in a week-long field study with 20 participants. In testing, the model obtains a recall of 89% and a false positive rate of 5% on lab data. On field data, the model is able to predict each instantaneous self-report with an accuracy of 72%. PMID- 26543927 TI - puffMarker: A Multi-Sensor Approach for Pinpointing the Timing of First Lapse in Smoking Cessation. AB - Recent researches have demonstrated the feasibility of detecting smoking from wearable sensors, but their performance on real-life smoking lapse detection is unknown. In this paper, we propose a new model and evaluate its performance on 61 newly abstinent smokers for detecting a first lapse. We use two wearable sensors breathing pattern from respiration and arm movements from 6-axis inertial sensors worn on wrists. In 10-fold cross-validation on 40 hours of training data from 6 daily smokers, our model achieves a recall rate of 96.9%, for a false positive rate of 1.1%. When our model is applied to 3 days of post-quit data from 32 lapsers, it correctly pinpoints the timing of first lapse in 28 participants. Only 2 false episodes are detected on 20 abstinent days of these participants. When tested on 84 abstinent days from 28 abstainers, the false episode per day is limited to 1/6. PMID- 26543928 TI - Meeting report: BBRC Symposium on Trends in Biochemistry and Biophysics. PMID- 26543929 TI - Response. PMID- 26543931 TI - Regional Nodal Irradiation in Early-Stage Breast Cancer. PMID- 26543930 TI - [Not Available]. PMID- 26543933 TI - SA's happiness-and misery-index. PMID- 26543932 TI - Supervision: Clear direction. PMID- 26543934 TI - Cost awareness on the part of health professionals. PMID- 26543935 TI - Myasthenia gravis is a rare but treatable disease. PMID- 26543936 TI - 'Changing sides'-SAMA unionist now Limpopo's Health MEC. PMID- 26543937 TI - Pain management-the global sound of silence. PMID- 26543938 TI - Snipping away at the HIV pandemic, one foreskin at a time. PMID- 26543939 TI - Fits, faints and funny turns. PMID- 26543940 TI - An approach to the clinical assessment and management of syncope in adults. AB - Syncope, defined as a brief loss of consciousness due to an abrupt fall in cerebral perfusion, remains a frequent reason for medical presentation. The goals of the clinical assessment of a patient with syncope are twofold: (i) to identify the precise cause in order to implement a mechanism-specific and effective therapeutic strategy; and (ii) to quantify the risk to the patient, which depends on the underlying disease,rather than the mechanism of the syncope. Hence, a structured approach to the patient with syncope is required. History-taking remains the most important aspect of the clinical assessment. The classification of syncope is based on the underlying pathophysiological mechanism causing the event, and includes cardiac, orthostatic and reflex (neurally mediated) mechanisms. Reflex syncope can be categorised into vasovagal syncope (from emotional or orthostatic stress), situational syncope (due to specific situational stressors), carotid sinus syncope(from pressure on the carotid sinus, e.g. shaving or a tight collar), and atypical reflex syncope (episodes of syncope or reflex syncope that cannot be attributed to a specific trigger or syncope with an atypical presentation). Cardiovascular causes of syncope may be structural(mechanical) or electrical. Orthostatic hypotension is caused by an abnormal drop in systolic blood pressure upon standing, and is defined asa decrease of >20 mmHg in systolic blood pressure or a reflex tachycardia of >20 beats/minute within 3 minutes of standing. The main causes of orthostatic hypotension are autonomic nervous system failure and hypovolaemia. Patients with life-threatening causes of syncope should be managed urgently and appropriately. In patients with reflex or orthostatic syncope it is important to address any exacerbating medication and provide general measures to increase blood pressure, such as physical counter-pressure manoeuvres. Where heart disease is found to bet he cause of the syncope, a specialist opinion is warranted and where possible the problem should be corrected. It is important to remember that in any patient presenting with syncope the main objectives of management are to prolong survival, limit physical injuries and prevent recurrences. This can only be done if a patient is appropriately assessed at presentation, investigated as clinically indicated, and subsequently referred to a cardiologist for appropriate management. PMID- 26543941 TI - Reply: To PMID 25541666. PMID- 26543942 TI - Reply: To PMID 25541660. PMID- 26543943 TI - Reply: To PMID 25541654. PMID- 26543944 TI - Albrecht Von Graefe (1828-1870). PMID- 26543946 TI - Moritz Kaposi--Resurgent Dermatologist. PMID- 26543945 TI - Carlos Juan Finlay (1833-1915). PMID- 26543947 TI - Theodor Kocher and Thyroid. PMID- 26543948 TI - Dr. Robert Koch (1843-1910). PMID- 26543949 TI - Elie Metchnikoff (1845-1916). PMID- 26543950 TI - Wilhelm Konrad Roentgen (1845-1923). PMID- 26543951 TI - Alphonse Laveran (1845-1922). PMID- 26543952 TI - Ivan Pavlov (1849-1936). PMID- 26543953 TI - William Osler (1849-1919). PMID- 26543954 TI - William S Halstead Pioneer of Modern Surgery. PMID- 26543955 TI - William Gorgas & Panama Canal. PMID- 26543956 TI - Emil Adolf Von Behring (1854-1917). PMID- 26543957 TI - Sir David Bruce (1855-1931). PMID- 26543958 TI - Sir Ronald Ross (1857-1932). PMID- 26543959 TI - Oroya Fever and Daniel Carrion--A Fatal Quest. PMID- 26543960 TI - Oskar Minkowski & Pancreas. PMID- 26543961 TI - Sir Arthur Conan Doyle (1859 -1930). PMID- 26543962 TI - WM Haffkine (1860-1930). PMID- 26543963 TI - Enteric Fever, Eberth & Widal. PMID- 26543964 TI - Alzheimer's Disease. PMID- 26543965 TI - Charles Nicolle (1866-1936). PMID- 26543966 TI - Karl Landsteiner (1868-1943). PMID- 26543967 TI - Otto Loewi & Neurochemical Phenomena. PMID- 26543968 TI - Alexis Carrel (1873-1944). PMID- 26543969 TI - Sir Henry Dale, The Great Investigator. PMID- 26543970 TI - Albert Schweitzer (1875-1965). PMID- 26543971 TI - Ferdinand Sauerbruch: Pioneer Thoracic Surgeon. PMID- 26543972 TI - Hideyo Noguchi Syphilis, Oraya Fever and Leptospira. PMID- 26543973 TI - Jokichi Takamine-Forgotten Samurai Chemist. PMID- 26543974 TI - Sir Thomas Lewis (1881-1945). PMID- 26543975 TI - Sir Alexander Fleming (1881-1955). PMID- 26543976 TI - Kala-Azar (Leishmaniasis). PMID- 26543977 TI - Battista Grassi (1854-1925) & Malaria Controversy. PMID- 26543978 TI - Bernardo Houssay and Pituitary Gland. PMID- 26543979 TI - Selman Waksman and Streptomycin. PMID- 26543980 TI - Frederick Banting (1891-1941). PMID- 26543981 TI - James Black & Birth of Beta Blockers. PMID- 26543982 TI - Werner Forssmann--The Risk Taker. PMID- 26543983 TI - Daniel Bovet--Inventive Pharmacologist. PMID- 26543984 TI - Hans Selye (1907-1982). PMID- 26543985 TI - Heimlich Manoeuvre. PMID- 26543986 TI - Brazilian Viper and BP Control. PMID- 26543988 TI - Dengue An Escalating Problem. PMID- 26543987 TI - HIV/TB--An Unholy Alliance. PMID- 26543989 TI - Trypanosomiasis in India. PMID- 26543990 TI - Amazing Aspirin. PMID- 26543991 TI - Telemedicine. PMID- 26543992 TI - Electricity and The Heart--Philatelic Sequelae. PMID- 26543994 TI - Rabies--"Milwaukie Protocol". PMID- 26543993 TI - Diabetic Foot and Heberprot-P. PMID- 26543995 TI - [Adolescents and multiple sclerosis: pediatric care to adult care]. PMID- 26543996 TI - [Joint statement: working together]. PMID- 26543997 TI - [Health care system: the status quo is not an option]. PMID- 26543999 TI - [Laurentides/Lanaudiere: The Blue Bracelet]. PMID- 26543998 TI - [Campaign to act: "AVC VITE"]. PMID- 26544000 TI - [Modernize the management and governance: a challenge]. PMID- 26544001 TI - [The patient, his/her family and the community: for a doctor-patient partnership]. PMID- 26544002 TI - [Clinical leadership and management of chronic diseases: five projects]. PMID- 26544003 TI - [WeObservatory: in the service of women's health]. PMID- 26544005 TI - [Environmental health: a response]. PMID- 26544004 TI - [Africa: controlling HIV/AIDS, an objective to be achieved]. PMID- 26544006 TI - [The role of the community to act on the determinants of health]. PMID- 26544007 TI - [Benin healthy children. Louise Leduc saving Jean-Baptiste]. PMID- 26544008 TI - [Yoga: the heart's friend]. PMID- 26544009 TI - [Acute myocardial infarction? A one hour test]. PMID- 26544010 TI - [Frontotemporal dementia]. PMID- 26544011 TI - [Pregnancies in Quebec]. PMID- 26544012 TI - [Medications and esophageal injuries]. PMID- 26544013 TI - [High dose ibuprofen: risk of heart and vascular problems]. PMID- 26544014 TI - Doping-Induced Universal Conductance Fluctuations in GaN Nanowires. AB - The transport properties of Ge-doped single GaN nanowires are investigated, which exhibit a weak localization effect as well as universal conductance fluctuations at low temperatures. By analyzing these quantum interference effects, the electron phase coherence length was determined. Its temperature dependence indicates that in the case of highly doped nanowires electron-electron scattering is the dominant dephasing mechanism, while for the slightly doped nanowires dephasing originates from Nyquist-scattering. The change of the dominant scattering mechanism is attributed to a modification of the carrier confinement caused by the Ge-doping. The results demonstrate that the phase coherence length can be tuned by the donor concentration making Ge-doped GaN nanowires an ideal model system for studying the influence of impurities on quantum-interference effects in mesoscopic and nanoscale systems. PMID- 26544015 TI - Migration of Single Iridium Atoms and Tri-iridium Clusters on MgO Surfaces: Aberration-Corrected STEM Imaging and Ab Initio Calculations. AB - To address the challenge of fast, direct atomic-scale visualization of the migration of atoms and clusters on surfaces, we used aberration-corrected scanning transmission electron microscopy (STEM) with high scan speeds (as little as ~0.1 s per frame) to visualize the migration of (1) a heavy atom (Ir) on the surface of a support consisting of light atoms, MgO(100), and (2) an Ir3 cluster on MgO(110). Sequential Z-contrast images elucidate the surface transport mechanisms. Density functional theory (DFT) calculations provided estimates of the migration energy barriers and binding energies of the iridium species to the surfaces. The results show how the combination of fast-scan STEM and DFT calculations allow visualization and fundamental understanding of surface migration phenomena pertaining to supported catalysts and other materials. PMID- 26544016 TI - Systematic Reviews and Meta-Analyses - Literature-based Recommendations for Evaluating Strengths, Weaknesses, and Clinical Value. AB - Good quality systematic reviews (SRs) summarizing best available evidence can help inform clinical decisions, improv- ing patient and wound outcomes. Weak SRs can misinform readers, undermining care decisions and evidence-based practice. To examine the strengths and weaknesses of SRs and meta-analyses and the role of SRs in contemporary evidence-based wound care practice, and using the search terms systematic review, meta-analysis, and evidence-based practice, the authors searched Medline and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for important terminology and recommendations to help clinicians evaluate SRs with meta-analysis. Reputable websites, recent textbooks, and synthesized available literature also were reviewed to describe and summarize SR strengths and weaknesses. After developing a checklist for critically evaluating SR objectives, inclusion/exclusion criteria, study quality, data extraction and synthesis methods, meta-analysis homogeneity, accuracy of results, interpretation, and consistency between significant findings and abstract or conclusions, the checklist was applied to topical wound care SRs identified in Cochrane and MEDLINE searches. Best available evidence included in the SRs from 169 randomized controlled trials on 11,571 patients supporting topical intervention healing effects on burns, surgical sites, and diabetic, venous, or pressure ulcers was summarized and showed SRs and clinical trials can demonstrate different outcomes because the information/data are compiled differently. The results illustrate how evidence insufficient to support firm conclusions may still meet immediate needs to guide carefully considered clinical wound and patient care decisions while encouraging better future science. PMID- 26544017 TI - A Retrospective Quality Improvement Study Comparing Use Versus Nonuse of a Padded Heel Dressing to Offload Heel Ulcers of Different Etiologies. AB - Offloading heel ulcers is a challenging task because strategies deemed to be most optimal from a medical perspective may be unacceptable to patients. Observed adverse dressing events and problems with offloading devices led to a pilot study and subsequent change in practice at the authors' Foot and Leg Ulcer Clinic. Starting in 2004, patients requiring offloading received a nonremovable padded heel dressing (PHD) that was changed twice a week by the visiting nurse. A retrospective quality improvement review was conducted to compare outcomes, nursing visits, and nursing visit costs for 40 consecutive patients with heel ulcers treated at this clinic with a nonremovable PHD (n = 20) or without a PHD (n = 20) between January 20, 2001 and December 31, 2006. Patient demographic data, relevant comorbidities, wound depth, weeks of care, adverse events, and treatment-related narrative comments were abstracted from patient records. Relevant comorbidities were similar in both groups. The PHD group was younger (average age of 74.6 [range 35-91] years) compared to PHD nonuse group (average age 79.5 [range 25-95] years; P less than 0.04). The PHD group required fewer total weeks of care compared to the nonuse group (368 versus 527 weeks, respectively; P less than 0.001), and average duration of clinic treatment in the PHD group was 18.40 (range 5-51) weeks versus 40.54 (range 6-88) weeks in the nonuse group. The PHD group had fewer total nursing visits (736 versus 1,581, P less than 0.001); the average number of nursing visits for the PHD was 36.80 (range 10-102) compared to 121.61 (range 18-264) for the nonuse group. Nursing visit costs were lower for PHD users ($114,080 versus $245,055, P less than 0.001), and the cost-efficiency ratio was less than one third (1:3.3) of PHD nonuse for the average heel ulcer. All 20 patients in the PHD use group had wound closure compared with the PHD nonuse group, in which 13 out of 20 wounds closed, 3 amputations were performed, and 4 patients were lost to review (P less than 0.000). No adverse events were reported in the records of the PHD use group; the PHD nonuse group reported periwound maceration, skin stripping, pressure injury, and sensitivity. Patient and nurse feedback identified pain relief, improved mobility, easy technique, low cost, and reduced workload as benefits of PHD. The results of this quality improvement review warrant a prospective clinical study to examine the efficacy, effectiveness, and cost-effectiveness of PHD for the care of patients with heel ulcers. PMID- 26544018 TI - Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B. AB - Irciniastatin A (a.k.a. psymberin) and irciniastatin B are members of the pederin natural product family, which have potent antitumor activity and structural complexity. Herein, we describe a full account of our total synthesis of (+) irciniastatin A and (-)-irciniastatin B. Our synthesis features the highly regioselective Eu(OTf)3-catalyzed, DTBMP-assisted epoxide ring opening reaction with MeOH, which enabled a concise synthesis of the C1-C6 fragment, extensive use of AZADO (2-azaadamantane N-oxyl) and its related nitroxyl radical/oxoammonium salt-catalyzed alcohol oxidation throughout the synthesis, and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. In addition, for the synthesis of (-)-irciniastatin B, we achieved the C11-selective control of the oxidation stage via regioselective deprotection and AZADO-catalyzed alcohol oxidation. The synthetic irciniastatins showed high levels of cytotoxic activity against mammalian cells. Furthermore, chemical footprinting experiments using synthetic compounds revealed that the binding site of irciniastatins is the E-site of the ribosome. PMID- 26544019 TI - Facile Synthesis of Biocompatible Fluorescent Nanoparticles for Cellular Imaging and Targeted Detection of Cancer Cells. AB - In this work, we report the facile synthesis of functional core-shell structured nanoparticles with fluorescence enhancement, which show specific targeting of cancer cells. Biopolymer poly-l-lysine was used to coat the silver core with various shell thicknesses. Then, the nanoparticles were functionalized with folic acid as a targeting agent for folic acid receptor. The metal-enhanced fluorescence effect was observed when the fluorophore (5-(and-6) carboxyfluorescein-succinimidyl ester) was conjugated to the modified nanoparticle surface. Cellular imaging assay of the nanoparticles in folic acid receptor-positive cancer cells showed their excellent biocompatibility and selectivity. The as-prepared functional nanoparticles demonstrate the efficiency of the metal-enhanced fluorescence effect and provide an alternative approach for the cellular imaging and targeting of cancer cells. PMID- 26544020 TI - Enhanced Radiation Resistance of Methanosarcina soligelidi SMA-21, a New Methanogenic Archaeon Isolated from a Siberian Permafrost-Affected Soil in Direct Comparison to Methanosarcina barkeri. AB - Permafrost-affected soils are characterized by a high abundance and diversity of methanogenic communities, which are considered suitable model organisms for potential life on Mars. Methanogens from Siberian permafrost have been proven to be highly resistant against divers stress conditions such as subzero temperatures, desiccation, and simulated thermophysical martian conditions. Here, we studied the radiation resistance of the currently described new species Methanosarcina soligelidi SMA-21, which was isolated from a Siberian permafrost affected soil, in comparison to Methanosarcina barkeri, which is used as a reference organism from a nonpermafrost soil environment. Both strains were exposed to solar UV and ionizing radiation to assess their limits of survival. Methanosarcina soligelidi exhibit an increase in radiation resistance to UV (2.5- to 13.8-fold) and ionizing radiation (46.6-fold) compared to M. barkeri. The F10 (UVC) and D10 (X-rays) values of M. soligelidi are comparable to values for the well-known, highly radioresistant species Deinococcus radiodurans. In contrast, the radiation response of M. barkeri was highly sensitive to UV and ionizing radiation comparably to Escherichia coli and other radiosensitive microorganisms. This study showed that species of the same genus respond differently to UV and ionizing radiation, which might reflect the adaptation of Methanosarcina soligelidi SMA-21 to the harsh environmental conditions of the permafrost habitat. KEY WORDS: Methanogenic archaea-Environmental UV-Ionizing radiation Permafrost-Radiation resistance-Mars. PMID- 26544021 TI - Modeling the Current and Future Roles of Particulate Organic Nitrates in the Southeastern United States. AB - Organic nitrates are an important aerosol constituent in locations where biogenic hydrocarbon emissions mix with anthropogenic NOx sources. While regional and global chemical transport models may include a representation of organic aerosol from monoterpene reactions with nitrate radicals (the primary source of particle phase organic nitrates in the Southeast United States), secondary organic aerosol (SOA) models can underestimate yields. Furthermore, SOA parametrizations do not explicitly take into account organic nitrate compounds produced in the gas phase. In this work, we developed a coupled gas and aerosol system to describe the formation and subsequent aerosol-phase partitioning of organic nitrates from isoprene and monoterpenes with a focus on the Southeast United States. The concentrations of organic aerosol and gas-phase organic nitrates were improved when particulate organic nitrates were assumed to undergo rapid (tau = 3 h) pseudohydrolysis resulting in nitric acid and nonvolatile secondary organic aerosol. In addition, up to 60% of less oxidized-oxygenated organic aerosol (LO OOA) could be accounted for via organic nitrate mediated chemistry during the Southern Oxidants and Aerosol Study (SOAS). A 25% reduction in nitrogen oxide (NO + NO2) emissions was predicted to cause a 9% reduction in organic aerosol for June 2013 SOAS conditions at Centreville, Alabama. PMID- 26544022 TI - Controlling Central Carbon Metabolism for Improved Pathway Yields in Saccharomyces cerevisiae. AB - Engineering control of metabolic pathways is important to improving product titers and yields. Traditional methods such as overexpressing pathway enzymes and deleting competing ones are restricted by the interdependence of metabolic reactions and the finite nature of cellular resources. Here, we developed a metabolite valve that controls glycolytic flux through central carbon metabolism in Saccharomyces cerevisiae. In a Hexokinase 2 and Glucokinase 1 deleted strain (hxk2Deltaglk1Delta), glucose flux was diverted away from glycolysis and into a model pathway, gluconate, by controlling the transcription of Hexokinase 1 with the tetracycline transactivator protein (tTA). A maximum 10-fold decrease in hexokinase activity resulted in a 50-fold increase in gluconate yields, from 0.7% to 36% mol/mol of glucose. The reduction in glucose flux resulted in a significant decrease in ethanol byproduction that extended to semianaerobic conditions, as shown in the production of isobutanol. This proof-of-concept is one of the first demonstrations in S. cerevisiae of dynamic redirection of glucose from glycolysis and into a heterologous pathway. PMID- 26544023 TI - The complete nucleotide sequence of the mitochondrial genome of Drosophila formosana (Diptera: Drosophilidae). AB - Drosophila formosana (Diptera: Drosophilidae) belongs to the Drosophilidae group of Drosophila. The mitochondrial genome sequence of Drosophila formosana is determined in this study. Mitochondrion of D. formosana is a circular DNA molecule of the 16 100 nucleotide pairs (bp) that contains one encoding region including 37 genes and 1 non-coding A + T-rich region. The similarity and typicality have been showed by the structure and organization analysis. All genes are arranged in the circular DNA molecule. In addition to DN5 that use GTG start codon, all other protein-coding genes (PCGs) start with an ATN start codon. Ten protein-coding genes stop with the termination codon TAN, while other protein coding genes (PCGs) used incomplete termination codon TA- (cox2, nad5, nad1). The A + T-rich region with a length of 1088 bp is located between rrnS and trnI. The mitochondrial genome of D. formosana has been completely sequenced for the first time in this study. PMID- 26544024 TI - Modulating the Stability of 2-Pyridinyl Thermolabile Hydroxyl Protecting Groups via the "Chemical Switch" Approach. AB - A novel and effective method is presented for modulating the stability of 2 Pyridinyl Thermolabile Protecting Groups (2-Py TPGs) in the "chemical switch" approach. The main advantage of the discussed approach is the possibility of changing the nucleophilic character of pyridine nitrogen using different switchable factors, which results in an increase or decrease in the thermal deprotection rate. One of the factors is transformation of a nitro into an amine group via reduction with a low-valent titanium in mild conditions. The usefulness of our approach is corroborated using 3'-O-acetyl nucleosides as model compounds. Their stability in various solvents and temperatures before and after reduction is also examined. Pyridine N-oxide and pH are other factors responsible for the nucleophilicity and stability of 2-Pyridinyl Thermolabile Protecting Groups in thermal deprotection. Protonation of 4-amino 2-Pyridinyl Thermolabile Protecting Groups is demonstrated by (1)H-(15)N HMBC and HSQC NMR analysis. PMID- 26544025 TI - Risk factors for intra-operative haemorrhage and bleeding risk scoring system for caesarean scar pregnancy: a case-control study. AB - OBJECTIVES: To investigate risk factors associated with excessive intra-operative haemorrhage during evacuation operation, and to develop a bleeding risk scoring system in patients with caesarean scar pregnancy (CSP) to guide treatment. STUDY DESIGN: A case-control study was conducted. Excessive intra-operative haemorrhage was defined as active bleeding during dilation and suction evacuation (blood loss >=200ml). The bleeding group consisted of patients who experienced excessive intra-operative blood loss. Patients with less intra-operative blood loss were included in the control group. RESULTS: In total, 458 admissions from 2009 to 2014 were included in this study. Compared with the control group, the bleeding group had higher serum beta-human chorionic gonadotrophin (hCG), higher gestational age, larger CSP mass, richer peritrophoblastic perfusion and thinner myometrial layer before evacuation (all p<0.05). Risk factors with p<0.05 on multivariable logistic regression analysis included serum beta-hCG >20,000mIU/ml [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0-3.2], gestational age >8 weeks (OR 2.1, 95% CI 1.1-4.0), maximum diameter of gestational sac or CSP mass >=5cm (OR 7.4, 95% CI 3.4-16.1), myometrial thickness <=0.15cm (OR 3.6, 95% CI 1.9-6.9) and significant peritrophoblastic perfusion (OR 9.8, 95% CI 4.1-23.2). These risk factors formed the final bleeding risk scoring system by conversion of their OR values into corresponding points. A total of 10 points was identified as the optimal cut-off on the receiver operating characteristic curve. Thus, patients with scores >=10 points were identified as being at high risk of bleeding. The final bleeding risk scoring system had an area under the curve of 0.86, sensitivity of 86.8% and specificity of 73.2%. CONCLUSIONS: Gestational age, serum beta-hCG, size of gestational sac, thickness of myometrial layer and peritrophoblastic perfusion were found to be associated with excessive intra operative haemorrhage during suction evacuation of CSP. A bleeding risk scoring system was constructed to help guide the management of patients with CSP. Patients with total scores >=10 points were identified as being at high risk of bleeding, whereas patients with total scores <=5 points were identified as being at low risk of bleeding. PMID- 26544026 TI - Uterine rupture without previous caesarean delivery: a population-based cohort study. AB - OBJECTIVE: To determine incidence and patient characteristics of women with uterine rupture during singleton births at term without a previous caesarean delivery. STUDY DESIGN: Population based cohort study. Women with term singleton birth, no record of previous caesarean delivery and planned vaginal delivery (n=611,803) were identified in the Danish Medical Birth Registry (1997-2008). Medical records from women recorded with uterine rupture during labour were reviewed to ascertain events of complete uterine rupture. Relative Risk (RR) and adjusted Relative Risk Ratio (aRR) of complete uterine rupture with 95% confidence intervals (95% CI) were ascertained according to characteristics of the women and of the delivery. RESULTS: We identified 20 cases with complete uterine rupture. The incidence of complete uterine rupture among women without previous caesarean delivery was about 3.3/100,000 deliveries. Multiparity (RR 8.99 (95% CI 1.86-43.29)), induction of labour (RR 3.26 (95% CI 1.24-8.57)), epidural analgesia (RR 10.78 (95% CI 4.25-27.39)), and augmentation by oxytocin (RR 9.50 (95% CI 3.15-28.63)) were associated with uterine rupture. Induction of labour was not significantly related to uterine rupture when adjusted for parity, epidural analgesia and augmentation by oxytocin. CONCLUSION: Although uterine rupture is rare, its association with epidural analgesia and augmentation of labour with oxytocin in multipara should be considered. Thus, vigilance should be exercised when labour is obstructed and there is need for epidural analgesia and/or augmentation by oxytocin in multiparous women. Due to the rare occurrence of uterine rupture caution should be exerted when interpreting the findings of this study. PMID- 26544027 TI - From disorders of consciousness to early neurorehabilitation using assistive technologies in patients with severe brain damage. AB - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the latest challenges addressed by neurorehabilitation initiated very early after the brain damage, such as dealing with disorders of consciousness in terms of diagnosis, prognosis and rehabilitative treatment, or determining best timing for first rehabilitative intervention, best therapeutic approaches and best modalities. RECENT FINDINGS: Early management of patients with severe brain damage requires a multidisciplinary rehabilitative approach that encompasses clinical skills in various fields, standard therapies, and assistive technologies.Despite a high rate of misdiagnosis and poor outcome prediction in disorders of consciousness, the observation of subtle motor signs may be a promising way to reach accurate diagnosis and better outcome prediction. Neurosensory stimulation remains the current treatment to promote emergence from disorders of consciousness.Early timing of neurological rehabilitation is definitively efficient, but a safety period should be respected. Some standard therapies and assistive technologies have demonstrated explicit evidence in neurological recovery and high treatment dose is needed to emphasize the therapeutic effect, but several controversies persist in treatment evidence. SUMMARY: Current advancements have provided growing evidence for early neurorehabilitation, which should be definitively applied, but further studies are explicitly needed to diminish persistent controversies in the field. PMID- 26544028 TI - Bilingualism, dementia, cognitive and neural reserve. AB - PURPOSE OF REVIEW: We discuss the role of bilingualism as a source of cognitive reserve and we propose the putative neural mechanisms through which lifelong bilingualism leads to a neural reserve that delays the onset of dementia. RECENT FINDINGS: Recent findings highlight that the use of more than one language affects the human brain in terms of anatomo-structural changes. It is noteworthy that recent evidence from different places and cultures throughout the world points to a significant delay of dementia onset in bilingual/multilingual individuals. This delay has been reported not only for Alzheimer's dementia and its prodromal mild cognitive impairment phase, but also for other dementias such as vascular and fronto-temporal dementia, and was found to be independent of literacy, education and immigrant status. SUMMARY: Lifelong bilingualism represents a powerful cognitive reserve delaying the onset of dementia by approximately 4 years. As to the causal mechanism, because speaking more than one language heavily relies upon executive control and attention, brain systems handling these functions are more developed in bilinguals resulting in increases of gray and white matter densities that may help protect from dementia onset. These neurocognitive benefits are even more prominent when second language proficiency and exposure are kept high throughout life. PMID- 26544030 TI - Traumatic brain injury: recent advances in plasticity and regeneration. AB - PURPOSE OF REVIEW: There is an urgent need for effective therapies to restore neurologic function and decrease disability following traumatic brain injury (TBI). Here, emerging findings on the mechanisms of post-TBI neural repair and regeneration, as well as therapeutic implications, are selectively reviewed. RECENT FINDINGS: Recent discoveries include the characterization of the inhibitory signaling systems within the injury site, postinjury stem cell niche activation, the role of serotonin signaling in repair, and environment enrichment. A potentially transformative finding has been the identification of exosomes, nano-sized extracellular vesicles which have key roles in cell signaling, and might serve as novel biomarkers and as vehicles for targeted delivery of repair-inducing molecules. SUMMARY: In the experimental setting, post TBI repair can be promoted by modulation of inhibitory signaling, neurotrophic factor administration, and amplified serotonin signaling; additional strategies include mobilization of endogenous stem cell populations, exogenous cell-based therapies, and environmental enhancement. Feasibility, safety, and efficacy of these approaches need further investigation in humans. Studies are also needed to evaluate biomarkers based on molecular traces of neural repair and regeneration, which could transform prognostic and predictive modeling of post-TBI recovery trajectories. PMID- 26544031 TI - Editorial. PMID- 26544029 TI - Neural interfaces for somatosensory feedback: bringing life to a prosthesis. AB - PURPOSE OF REVIEW: When an individual loses a limb, he/she loses touch with the world and with the people around him/her. Somatosensation is critical to the feeling of connection and control of one's own body. Decades of attempts to replace lost somatosensation by sensory substitutions have been ineffective outside of the laboratory. This review discusses important recent results demonstrating chronic somatosensory restoration through direct peripheral nerve stimulation. RECENT FINDINGS: Stimulation of peripheral nerves results in somatosensory perception on the phantom limb. Sensations are localized to several independent and functionally relevant locations, such as the fingertips, thenar eminence, ulnar border and dorsal surface. Patterns in stimulation intensity change the perception experience by the user, opening new dimensions on neuromodulation. SUMMARY: Neural interfaces with sophisticated stimulation paradigms create a user's perception of his/her hand to touch and manipulate objects. The pattern of intensity and frequency of stimulation is critical to the quality and intensity of perceived sensation. Restoring feeling has allowed the individuals to, 'feel [my] hand for the first time since the accident,' and 'feel [my] wife touch my hand'. Individuals using a prosthetic hand with sensation can pull cherries and grapes from the stem, open water bottles and move objects without destroying these objects - all while audio and visually deprived. After regaining sensation, phantom pain is eliminated in individuals that had frequent, sometimes debilitating, pain following limb loss. With over 5 subject-years of experience, this work is leading the evolution of a new era in prostheses. Somatosensory prosthetics as a standard procedure to augment and restore somatosensation are now within our reach. PMID- 26544032 TI - Reducing Loss to Follow-Up with Tele-audiology Diagnostic Evaluations. AB - BACKGROUND: Infants who do not pass their newborn hearing screen require diagnostic follow-up visits but often face access barriers such as travel distance and shortage of pediatric audiologists. Telemedicine (tele-audiology) is a potential solution to provide diagnostic hearing evaluations for families of infants facing access barriers. We determined the feasibility and impact of a tele-audiology program that provided comprehensive diagnostic evaluations to a region with a high lost to follow-up rate among newborns who did not pass their newborn hearing screen. MATERIALS AND METHODS: We evaluated the tele-audiology program using parent and provider surveys to determine the perception of quality and satisfaction of care. We also compared the lost to follow-up rate of the tele audiology program with the loss to follow-up in the region before the implementation of the program. RESULTS: Twenty-two infants who did not pass their newborn hearing screen were referred to the tele-audiology program for diagnostic evaluation. Among these infants, 59.1% were diagnosed with some form of hearing loss. The mean quality score rated by both parents and providers on the telemedicine interaction was over 6.5 on a 7-point Likert scale. All parents rated the importance of tele-audiology as 7 (extremely important) for their family, whereas the provider rated the mean importance as 6.4 (95% confidence interval, 5.9, 6.9) on a 7-point Likert scale. Almost all parents actively participated or were engaged during history taking and counseling and were comfortable in discussing their child's hearing status remotely over telemedicine. All infants completed their diagnostic evaluation with no loss to follow-up compared with 22% loss to follow-up in the region before the implementation of the program. CONCLUSIONS: Tele-audiology is a feasible solution that reduces the loss to follow-up among infants who do not pass their newborn hearing screen and have access barriers to qualified audiologists for diagnostic evaluations. PMID- 26544033 TI - Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection. AB - The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARgamma and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design. PMID- 26544034 TI - Effect of Er,Cr:YSGG Laser at Different Output Powers on the Micromorphology and the Bond Property of Non-Carious Sclerotic Dentin to Resin Composites. AB - BACKGROUND: The objective of this study was to investigate the influence of Er,Cr:YSGG laser irradiated at different powers on the micromorphology and the bonding property of non-carious sclerotic dentin to resin composites. METHODS: Two hundred bovine incisors characterized by non-carious sclerotic dentin were selected, and the seventy-two teeth of which for surface morphological analysis were divided into nine groups according to various treatments (A: the control group, B: only treated with the adhesive Adper Easy One, C: diamond bur polishing followed by Adper Easy One, D-I: Er,Cr:YSGG laser irradiating at 1W, 2W, 3W, 4W, 5W, 6W output power, respectively, followed by Adper Easy One). The surface roughness values were measured by the non-contact three-dimensional morphology scanner, then the surface micromorphologies of surfaces in all groups were assessed by scanning electron microscopy (SEM); meanwhile, Image Pro-Plus 6.0 software was used to measure the relative percentage of open tubules on SEM images. The rest, one hundred twenty-eight teeth for bond strength test, were divided into eight groups according to the different treatments (A: only treated with the adhesive Adper Easy One, B: diamond bur polishing followed by the above adhesive, C-H: Er,Cr:YSGG laser irradiating at 1 W, 2 W, 3 W, 4 W, 5 W, 6 W output power, respectively, followed by the above adhesive), and each group was subsequently divided into two subgroups according to whether aging is performed (immediately tested and after thermocycling). Micro-shear bond strength test was used to evaluate the bond strength. RESULTS: The 4W laser group showed the highest roughness value (30.84+/-1.93MUm), which was statistically higher than the control group and the diamond bur groups (p<0.05). The mean percentages ((27.8+/-1.8)%, (28.0+/-2.2)%, (30.0+/-1.9)%) of open tubules area in the 4W, 5W, 6W group were higher than other groups (p<0.05). The 4W laser group showed the highest micro-shear bond strength not only in immediately tested (17.60+/-2.55 PMa) but after thermocycling (14.35+/-2.08MPa). CONCLUSION: The Er,Cr:YSGG laser at 4W power can effectively improve the bonding property between non-carious sclerotic dentin and resin composites by increasing the roughness and mean percentage area of open tubules. PMID- 26544035 TI - The Effect of Calcium Sodium Phosphosilicate on Dentin Hypersensitivity: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: To investigate the effect of calcium sodium phosphosilicate (CSPS) in treating dentin hypersensitivity (DH) and to compare this effect to that of a negative (placebo) control. MATERIALS AND METHODS: Several databases, including Medline, EMBASE, Web of Science, The Cochrane Library, and the Chinese Biomedical Literature Database, were searched to identify relevant articles published through January 2015; grey literature (i.e., academic literature that is not formally published) was also searched. Two authors performed data extraction independently and jointly using data collection forms. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative, or electrical stimuli, and the secondary outcome was the side effects of CSPS use. Each study was evaluated using the Cochrane Collaboration tool for assessing risk bias. Meta-analysis of studies with the same participant demographics, interventions, controls, assessment methods and follow-up periods was performed. The Grading of Recommendations Assessment Development and Evaluation System was used to assess the quality of the evidence and the risk of bias across studies. RESULTS: Meta-analysis demonstrated that toothpaste containing 5% CSPS was more effective than the negative control at relieving dentin sensitivity, with the level of evidence classified as "moderate". In addition, prophylaxis paste containing 15% calcium sodium phosphosilicate was favored over the negative control at reducing post-periodontal therapy hypersensitivity, with the level of evidence categorized as "low". Only two studies reported side effects of CSPS use. CONCLUSIONS: The majority of studies found that calcium sodium phosphosilicate was more effective than the negative control at alleviating DH. Because strong evidence is scarce, high-quality, well-designed clinical trials are required in the future before definitive recommendations can be made. PMID- 26544036 TI - The Paternal Landscape along the Bight of Benin - Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers. AB - Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY) has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample. Therefore, the uniquely and powerful geographical information carried by the Y chromosome makes it an important locus to test the representativeness of a certain sample even in the genomic era, especially in poorly investigated areas like Africa. PMID- 26544037 TI - A Tandem Oligonucleotide Approach for SNP-Selective RNA Degradation Using Modified Antisense Oligonucleotides. AB - Antisense oligonucleotides have been studied for many years as a tool for gene silencing. One of the most difficult cases of selective RNA silencing involves the alleles of single nucleotide polymorphisms, in which the allele sequence is differentiated by a single nucleotide. A new approach to improve the performance of allele selectivity for antisense oligonucleotides is proposed. It is based on the simultaneous application of two oligonucleotides. One is complementary to the mutated form of the targeted RNA and is able to activate RNase H to cleave the RNA. The other oligonucleotide, which is complementary to the wild type allele of the targeted RNA, is able to inhibit RNase H cleavage. Five types of SNPs, C/G, G/C, G/A, A/G, and C/U, were analyzed within the sequence context of genes associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, ALS (Amyotrophic Lateral Sclerosis), and Machado-Joseph disease. For most analyzed cases, the application of the tandem approach increased allele-selective RNA degradation 1.5-15 fold relative to the use of a single antisense oligonucleotide. The presented study proves that differentiation between single substitution is highly dependent on the nature of the SNP and surrounding nucleotides. These variables are crucial for determining the proper length of the inhibitor antisense oligonucleotide. In the tandem approach, the comparison of thermodynamic stability of the favorable duplexes WT RNA-inhibitor and Mut RNA-gapmer with the other possible duplexes allows for the evaluation of chances for the allele-selective degradation of RNA. A larger difference in thermodynamic stability between favorable duplexes and those that could possibly form, usually results in the better allele selectivity of RNA degradation. PMID- 26544038 TI - A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo. AB - Long-term potentiation (LTP) and long-term depression (LTD) are widely accepted to be synaptic mechanisms involved in learning and memory. It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals. Recent experiments in the dentate gyrus of freely moving rats revealed an unexpected pattern of LTP and LTD from high frequency perforant path stimulation. While 400 Hz theta-burst stimulation (400 TBS) and 400 Hz delta-burst stimulation (400-DBS) elicited substantial LTP of the tetanized medial path input and, concurrently, LTD of the non-tetanized lateral path input, 100 Hz theta-burst stimulation (100-TBS, a normally efficient LTP protocol for in vitro preparations) produced only weak LTP and concurrent LTD. Here we show in a biophysically realistic compartmental granule cell model that this pattern of results can be accounted for by a voltage-based spike-timing dependent plasticity (STDP) rule combined with a relatively fast Bienenstock Cooper-Munro (BCM)-like homeostatic metaplasticity rule, all on a background of ongoing spontaneous activity in the input fibers. Our results suggest that, at least for dentate granule cells, the interplay of STDP-BCM plasticity rules and ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighboring non-tetanized inputs, as generated by the ongoing constitutive activity at these synapses. PMID- 26544039 TI - Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions. AB - OBJECTIVE: We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. METHODS: Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. RESULTS: Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). CONCLUSIONS: We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results. PMID- 26544040 TI - Genetic Analysis of Norovirus GII.4 Variant Strains Detected in Outbreaks of Gastroenteritis in Yokohama, Japan, from the 2006-2007 to the 2013-2014 Seasons. AB - Noroviruses (NoVs) are the leading cause of acute gastroenteritis, both in sporadic cases and outbreaks. Since the 1990s, the emergence of several GII.4 variants has been reported worldwide. To investigate the epidemic status of NoV, 6,724 stool samples collected from outbreaks in Yokohama, Japan, from the 2006 2007 to 2013-2014 seasons were assessed for NoVs. We genotyped one specimen from each GII outbreak and conducted a sequence analysis of the VP1 gene for several GII.4 strains. Of the 947 NoV outbreaks during our study, GII was detected in 835, and GII.4 was the predominant genotype of GII. Five different GII.4 variants, Yerseke 2006a, Den Haag 2006b (2006b), Apeldoorn 2007, New Orleans 2009, and Sydney 2012, were detected. During this study period, the most prevalent variant of GII.4 was 2006b, and in each individual season, either 2006b or Sydney 2012 was the predominant variant. Out of the 16 detected 2006b strains, 12 had some amino acid substitutions in their blockade epitope, and these substitutions were concentrated in three residues. Two of the 2006b strains detected in the 2012-2013 season had a S368E substitution, which is consistent with the amino acid residues at same site of NSW0514 (Sydney 2012 prototype). Among the 16 detected strains of Sydney 2012, a phylogenetic analysis showed that all five strains detected in Yokohama during the 2011-2012 season clustered away from the other Sydney 2012 strains that were detected in the 2012-2013 and 2013 2014 seasons. These five strains and other Sydney 2012 strains in Yokohama had a few amino acid differences in the blockade epitopes compared with NSW0514. The amino acid substitutions observed in this study provide informative data about the evolution of a novel GII.4 variant. PMID- 26544041 TI - Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. AB - OBJECTIVE: Epilepsy and intellectual/developmental disabilities (ID/DD) have a high rate of co-occurrence. Here, we investigated gene mutations in Chinese children with unexplained epilepsy and ID/DD. METHODS: We used targeted next generation sequencing to detect mutations within 300 genes related to epilepsy and ID/DD in 253 Chinese children with unexplained epilepsy and ID/DD. A series of filtering criteria was used to find the possible pathogenic variations. Validation and parental origin analyses were performed by Sanger sequencing. We reviewed the phenotypes of patients with each mutated gene. RESULTS: We identified 32 novel and 16 reported mutations within 24 genes in 46 patients. The detection rate was 18% (46/253) in the whole group and 26% (17/65) in the early onset (before three months after birth) epilepsy group. To our knowledge, we are the first to report KCNAB1 is a disease-causing gene of epilepsy by identifying a novel de novo mutation (c.1062dupCA p.Leu355HisfsTer5) within this gene in one patient with early infantile epileptic encephalopathy (EIEE). Patients with an SCN1A mutation accounted for the largest proportion, 17% (8/46). A total of 38% (9/24) of the mutated genes re-occurred at least 2 times and 63% (15/24) occurred only one time. Ion channel genes are the most common (8/24) and genes related to synapse are the next most common to occur (5/24). SIGNIFICANCE: We have established genetic diagnosis for 46 patients of our cohort. Early-onset epilepsy had the highest detection rate. KCNAB1 mutation was first identified in EIEE patient. We expanded the phenotype and mutation spectrum of the genes we identified. The mutated genes in this cohort are mostly isolated. This suggests that epilepsy and ID/DD phenotypes occur as a consequence of brain dysfunction caused by a highly diverse population of mutated genes. Ion channel genes and genes related to synapse were more common mutated in this patient cohort. PMID- 26544043 TI - Enteral Nutrition: Whom, Why, When, What and Where to Feed? AB - Oral and enteral nutrition affects both the anatomical and physiological integrity of the gastrointestinal tract. It downregulates systemic immune response, reduces overall oxidative stress and limits systemic inflammatory responses. It reduces bacterial translocation, limits pathogenic bacteria in the intestines and enables the production of short-chain fatty acids in the colon. Therefore, it is the most physiologic way of providing nutritional support in all patients. The enteral formulas are available as polymeric, semi-elemental and elemental diets. The beneficial effects on the gastrointestinal tract and systemic organs of 'early' enteral nutrition depend on the timing, dose, location and different modalities of enteral delivery. Being familiar with the basic tenets of providing enteral nutrition - the 'Who, Why, When, Where and What' - will result in safe nutritional interventions and achieve a positive clinical outcome. PMID- 26544042 TI - Cross-Reactivity of Filariais ICT Cards in Areas of Contrasting Endemicity of Loa loa and Mansonella perstans in Cameroon: Implications for Shrinking of the Lymphatic Filariasis Map in the Central African Region. AB - BACKGROUND: Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1-39.0; p < 0.001). Similarly, a strong positive association (Spearman's rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results was found only in areas with an L. loa Mf prevalence above 15%. In contrast, there was no association between ICT positivity and M. perstans prevalence (Spearman's rho = - 0.200; p = 0.747) and Mf density (Odds ratio = 1.8; 95%CI: 0.8-4.2; p = 0.192). CONCLUSIONS/SIGNIFICANCE: This study has confirmed the strong association between the ICT positivity and L. loa intensity (Mf/ml of blood) at the individual level. Furthermore, the study has demonstrated that ICT positivity is strongly associated with high L. loa prevalence. These results suggest that the main confounding factor for positive ICT test card results are high levels of L. loa. The findings may indicate that W. bancrofti is much less prevalent in the Central African region where L. loa is highly endemic than previously assumed and accurate re-mapping of the region would be very useful for shrinking of the map of LF distribution. PMID- 26544044 TI - Circulating Stromal Cell-Derived Factor 1alpha Levels in Heart Failure: A Matter of Proper Sampling. AB - BACKGROUND: The chemokine Stromal cell-derived factor 1alpha (SDF1alpha, CXCL12) is currently under investigation as a biomarker for various cardiac diseases. The correct interpretation of SDF1alpha levels is complicated by the occurrence of truncated forms that possess an altered biological activity. METHODOLOGY: We studied the immunoreactivities of SDF1alpha forms and evaluated the effect of adding a DPP4 inhibitor in sampling tubes on measured SDF1alpha levels. Using optimized sampling, we measured DPP4 activity and SDF1alpha levels in patients with varying degrees of heart failure. RESULTS: The immunoreactivities of SDF1alpha and its degradation products were determined with three immunoassays. A one hour incubation of SDF1alpha with DPP4 at 37 degrees C resulted in 2/3 loss of immunoreactivity in each of the assays. Incubation with serum gave a similar result. Using appropriate sampling, SDF1alpha levels were found to be significantly higher in those heart failure patients with a severe loss of left ventricular function. DPP4 activity in serum was not altered in the heart failure population. However, the DPP4 activity was found to be significantly decreased in patients with high SDF1alpha levels. CONCLUSIONS: We propose that all samples for SDF1alpha analysis should be collected in the presence of at least a DPP4 inhibitor. In doing so, we found higher SDF1alpha levels in subgroups of patients with heart failure. Our work supports the need for further research on the clinical relevance of SDF1alpha levels in cardiac disease. PMID- 26544045 TI - What Do Experienced Water Managers Think of Water Resources of Our Nation and Its Management Infrastructure? AB - This article represents the second report by an ASCE Task Committee "Infrastructure Impacts of Landscape-driven Weather Change" under the ASCE Watershed Management Technical Committee and the ASCE Hydroclimate Technical Committee. Herein, the 'infrastructure impacts" are referred to as infrastructure sensitive changes in weather and climate patterns (extremes and non-extremes) that are modulated, among other factors, by changes in landscape, land use and land cover change. In this first report, the article argued for explicitly considering the well-established feedbacks triggered by infrastructure systems to the land-atmosphere system via landscape change. In this report by the ASCE Task Committee (TC), we present the results of this ASCE TC's survey of a cross section of experienced water managers using a set of carefully crafted questions. These questions covered water resources management, infrastructure resiliency and recommendations for inclusion in education and curriculum. We describe here the specifics of the survey and the results obtained in the form of statistical averages on the 'perception' of these managers. Finally, we discuss what these 'perception' averages may indicate to the ASCE TC and community as a whole for stewardship of the civil engineering profession. The survey and the responses gathered are not exhaustive nor do they represent the ASCE-endorsed viewpoint. However, the survey provides a critical first step to developing the framework of a research and education plan for ASCE. Given the Water Resources Reform and Development Act passed in 2014, we must now take into account the perceived concerns of the water management community. PMID- 26544046 TI - Correction: Acute Fluoxetine Treatment Induces Slow Rolling of Leukocytes on Endothelium in Mice. PMID- 26544047 TI - Preparation of an Antibacterial Poly(ionic liquid) Graft Copolymer of Hydroxyethyl Cellulose. AB - Poly(ionic liquid)s (P(IL)s) of different degrees of polymerization (10, 50, and 100) were prepared via RAFT polymerization using an alkyne-terminated xanthate as transfer agent, with a monomer conversion of up to ~80% and a DM of 1.5 for P(IL)100. Subsequently, P(IL) chains were coupled to (15)N-labeled azido functionalized hydroxyethyl cellulose (HEC), forming graft copolymers of HEC with different chain length and graft densities, which were characterized using ((13)C and (15)N) CP-MAS NMR and FT-IR spectroscopies. The antibacterial activities of HEC-g-P(IL)s were tested against Escherichia coli and Staphylococcus aureus and were comparable to ampicillin, a well-known antibiotic, demonstrating efficient activity of the graft copolymers against bacteria. Moreover, HEC-g-P(IL)s were slightly more effective against E. coli than S. aureus. A decrease in graft density of P(IL)10 on the HEC backbone decreased the activity of the graft copolymers against both bacteria. These findings suggest that HEC-g-P(IL) could find applications as an antiseptic compound, for example, in paint formulation. PMID- 26544048 TI - Rasch Analysis of the Adult Strabismus Quality of Life Questionnaire (AS-20) among Chinese Adult Patients with Strabismus. AB - BACKGROUND: The impact of strabismus on visual function, self-image, self-esteem, and social interactions decrease health-related quality of life (HRQoL).The purpose of this study was to evaluate and refine the adult strabismus quality of life questionnaire (AS-20) by using Rasch analysis among Chinese adult patients with strabismus. METHODS: We evaluated the fitness of the AS-20 with Rasch model in Chinese population by assessing unidimensionality, infit and outfit, person and item separation index and reliability, response ordering, targeting and differential item functioning (DIF). RESULTS: The overall AS-20 did not demonstrate unidimensional; however, it was achieved separately in the two Rasch revised subscales: the psychosocial subscale (11 items) and the function subscale (9 items). The features of good targeting, optimal item infit and outfit, and no notable local dependence were found for each of the subscales. The rating scale was appropriate for the psychosocial subscale but a reduction to four response categories was required for the function subscale. No significant DIF were revealed for any demographic and clinical factors (e.g., age, gender, and strabismus types). CONCLUSION: The AS-20 was demonstrated by Rasch analysis to be a rigorous instrument for measuring health-related quality of life in Chinese strabismus patents if some revisions were made regarding the subscale construct and response options. PMID- 26544049 TI - Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress. AB - Members of the family of calcium dependent protein kinases (CDPK's) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3. Among these was Myosin A (TgMyoA), the unconventional motor protein greatly responsible for driving the gliding motility of this parasite, and whose phosphorylation at serine 21 by an unknown kinase was previously shown to be important for motility and egress. Through a non-biased peptide array approach we determined that TgCDPK3 can specifically phosphorylate serines 21 and 743 of TgMyoA in vitro. Complementation of the TgmyoA null mutant, which exhibits a delay in egress, with TgMyoA in which either S21 or S743 is mutated to alanine failed to rescue the egress defect. Similarly, phosphomimetic mutations in the motor protein overcome the need for TgCDPK3. Moreover, extracellular Tgcdpk3 mutant parasites have motility defects that are complemented by expression of S21+S743 phosphomimetic of TgMyoA. Thus, our studies establish that phosphorylation of TgMyoA by TgCDPK3 is responsible for initiation of motility and parasite egress from the host-cell and provides mechanistic insight into how this unique kinase regulates the lytic cycle of Toxoplasma gondii. PMID- 26544050 TI - Effects of Increased Summer Precipitation and Nitrogen Addition on Root Decomposition in a Temperate Desert. AB - BACKGROUND: Climate change scenarios that include precipitation shifts and nitrogen (N) deposition are impacting carbon (C) budgets in arid ecosystems. Roots constitute an important part of the C cycle, but it is still unclear which factors control root mass loss and nutrient release in arid lands. METHODOLOGY/PRINCIPAL FINDINGS: Litterbags were used to investigate the decomposition rate and nutrient dynamics in root litter with water and N-addition treatments in the Gurbantunggut Desert in China. Water and N addition had no significant effect on root mass loss and the N and phosphorus content of litter residue. The loss of root litter and nutrient releases were strongly controlled by the initial lignin content and the lignin:N ratio, as evidenced by the negative correlations between decomposition rate and litter lignin content and the lignin:N ratio. Fine roots of Seriphidium santolinum (with higher initial lignin content) had a slower decomposition rate in comparison to coarse roots. CONCLUSION/SIGNIFICANCE: Results from this study indicate that small and temporary changes in rainfall and N deposition do not affect root decomposition patterns in the Gurbantunggut Desert. Root decomposition rates were significantly different between species, and also between fine and coarse roots, and were determined by carbon components, especially lignin content, suggesting that root litter quality may be the primary driver of belowground carbon turnover. PMID- 26544052 TI - [Generating evidence for a better patients care]. PMID- 26544051 TI - Discovery of Genome-Wide Microsatellite Markers in Scombridae: A Pilot Study on Albacore Tuna. AB - Recent developments in sequencing technologies and bioinformatics analysis provide a greater amount of DNA sequencing reads at a low cost. Microsatellites are the markers of choice for a variety of population genetic studies, and high quality markers can be discovered in non-model organisms, such as tuna, with these recent developments. Here, we use a high-throughput method to isolate microsatellite markers in albacore tuna, Thunnus alalunga, based on coupling multiplex enrichment and next-generation sequencing on 454 GS-FLX Titanium pyrosequencing. The crucial minimum number of polymorphic markers to infer evolutionary and ecological processes for this species has been described for the first time. We provide 1670 microsatellite design primer pairs, and technical and molecular genetics selection resulting in 43 polymorphic microsatellite markers. On this panel, we characterized 34 random and selectively neutral markers ("neutral") and 9 "non-neutral" markers. The variability of "neutral" markers was screened with 136 individuals of albacore tuna from southwest Indian Ocean (42), northwest Indian Ocean (31), South Africa (31), and southeast Atlantic Ocean (32). Power analysis demonstrated that the panel of genetic markers can be applied in diversity and population genetics studies. Global genetic diversity for albacore was high with a mean number of alleles at 16.94; observed heterozygosity 66% and expected heterozygosity 77%. The number of individuals was insufficient to provide accurate results on differentiation. Of the 9 "non neutral" markers, 3 were linked to a sequence of known function. The one is located to a sequence having an immunity function (ThuAla-Tcell-01) and the other to a sequence having energy allocation function (ThuAla-Hki-01). These two markers were genotyped on the 136 individuals and presented different diversity levels. ThuAla-Tcell-01 has a high number of alleles (20), heterozygosity (87 90%), and assignment index. ThuAla-Hki-01 has a lower number of alleles (9), low heterozygosity (24-27%), low assignment index and significant inbreeding. Finally, the 34 "neutral" and 3 "non-neutral" microsatellites markers were tested on four economically important Scombridae species-Thunnus albacares, Thunnus thynnus, Thunnus obesus, and Acanthocybium solandri. PMID- 26544053 TI - [Validity and reproducibility of a food frequency questionnaire to assess lipid and phytochemical intake]. AB - BACKGROUND: epidemiological studies have been related food intake with the incidence of non-transmissible chronic diseases. OBJECTIVE: the purpose of the present study was to analyze the validity and reproducibility of a food frequency questionnaire (FFQ) aimed at assessing lipid and phytochemical intake. MATERIAL AND METHODS: FFQ was administered to 45 people of both sexes, aged between 20 and 72 years old and resident in Cordoba, Argentina. The FFQ included 257 questions referring to foods, their consumption frequency and portion size. Regarding consumption of fruit and vegetables, the season was also taken into account. The questionnaire was applied at two different periods (FFQ1 and FFQ2) with a break of six months in between. As a reference, the 24-hour dietary recall was used (24HDR) three times. The mid intake of FFQ1-FFQ2, the 24HDR-FFQ2 median intake, median difference, Mean Absolute Deviation from the median differences (MAD), Wilcoxon signed rank sum test and Spearman rank order correlation coefficients were calculated to analyze the accuracy of the FFQ data. RESULTS: the correlation coefficients for FFQ1-FFQ2 varied from 0.52 for 20:5 n3 eicosapentanoic (EPA) fatty acid to 0.89 for 4:0 butyric fatty acid (p<0.05). For 24HDR-FFQ2, the values ranged from 0.19 for lycopene to 0.93 for EPA fatty acid (p<0.05). CONCLUSION: the analysis carried out showed an acceptable validity and reproducibility of the FFQ, thus enabling it to be used in research relating the intake of lipids and phytochemicals and the risk of non-transmissible diseases. PMID- 26544054 TI - [Body profile and physical and cognitive function by age in ambulatory elderly women from the city of Cordoba]. AB - Aging produces body changes such as redistribution of fat and loss of muscle mass and strength, predisposing to fragility, functional impairment and disability. OBJECTIVE: To analyze the relationship between body profile and physical and cognitive function by age in in ambulatory elderly women from the city of Cordoba. METHODS: 178 healthy older women (OW) >=60 years free living were evaluated attending centers of retirees and day homes in the city of Cordoba. We evaluated body profile from: skeletal muscle mass index (SMMI), relative body adiposity (RBA) -dual X-ray absorptiometry- and muscle strength (MS) -dynamometry . Categories: normal/(N) sarcopenia/(SP), obesity/(OB), sarcopenic obesity/(SO); Physical function: with/without physical limitation (PL); cognitive function: with/without cognitive impairment (CI). INSTRUMENTS: Lunar Prodigy Densitometer and Smedley dynamometer, Lawton and Brody and Minimental Examination of Folstein scales. RESULTS: SO prevailed and increased with age, contrary to OB. Most of the OW did not PL or CI. Only 2.25% had low SMMI and 48.3% dynapenia. 76.97% had elevated RBA. The SP - obese or not - had greater PL and CI. CI frequency doubled to PL (15.17% versus 6.74%). We found negative correlations and significant associations between age and MS (r= -0.279; p=0.0001), physical function (r= 0.164; p=0.0283) and cognitive function (r=-0.028; p=0.0002). CONCLUSIONS: In this group of healthy OW the dynapenia was responsible for the observed SP, not low SMMI. The OW with SP had more PL and CI, and increased with age. PMID- 26544055 TI - [A comparison of two systems for hydration of children with diabetic ketoacidosis. a randomized controlled trial]. AB - BACKGROUND: Treatment of diabetic ketoacidosis (DKA) requires hourly controls of blood glucose, which define changes in the intravenous glucose and insulin administration. Every change requires preparing a new solution, wasting time and allowing errors. The two bag system (same electrolytes composition, but one with and the other without glucose) allows immediate changes in glucose administration rate, just by changing the solutions drip. OBJECTIVE: To compare the time needed to reach stabilization of patients with DKA using two different hydration systems: the traditional one (1 glucose/electrolyte solution) vs. the alternative one (2 glucose/electrolyte solutions -"two bag system"-). METHODS: Randomized controlled trial, including children aged 1 to 18 years, hospitalized for DKA (glycemia >200 mg/dl, pH <7.3, bicarbonate <15 mmol/L, glycosuria and ketonuria). After initial emergency re-hydration, patients were randomized to one of the 2 hydration systems (traditional or alternative), using it until patient stabilization (glycemia <=250 mg/dl, pH >= 7.3, bicarbonate >= 15 mmol/L); the time required to reach stabilization was the outcome variable. RESULTS: After enrolling 12 of the 32 planned subjects (6 in each group) Data Monitoring Committee performed a scheduled interim analysis, finding that the time required to reach stabilization was significantly shorter using the alternative system (9.8+/-1.16 hs vs. 13.3+/-2.8 hs; p=0.018). Because of the magnitude of this finding, the Ethics Committee decided to terminate the study. PMID- 26544056 TI - [Placental weight percentiles and its relationship with fetal weight according to gestational age in an urban area of Buenos Aires]. AB - BACKGROUND: The placental weight (PW) and the rates of their relationship with birth weight (BW) (BW / PW, PW / BW) predict perinatal morbidity and mortality and future health outcomes. OBJECTIVES: Estimate percentiles of PW and indices by sex and gestational age (GA) corresponding to 867 live born from Sarda Maternity of Buenos Aires and compare with international references. METHODS: Stillbirth, multiple pregnancy, gestational age <22 and > 42 weeks and PW <100g and > 2500g were excluded. Maternal and fetal characteristics were: age, education, smoking, parity, diabetes, preeclampsia, chorioamnionitis, growth restriction, prematurity and congenital anomalies. Summary statistics and percentiles with the LMS method were calculated. The comparisons were performed using Student t-test, ANOVA and international references. RESULTS: Average maternal age 24 years , education 10.1 years, 24.5% primiparous, 12.6% smokers, 4.9% had diabetes, 8.7% preeclampsia, 7.9% chorioamnionitis and 13.0% fetal growth restriction; 55.3% of newborns were male, 51.6% preterm, 18.9% small for gestational age and 7.1% malformed. On average BW and GA were 2581g and 35.6 weeks, respectively. High positive correlation between GA with PW and BW/PW, and negative with PW/BW was observed (p <0.001); placental weight and indices were higher in males. Percentiles of PW, BW / PW and PW / BW are depicted. Differences with references ranged from 0.46% 13%, 4.91% -12.1% and 5.81% -14% for PW, BW / PW and PW / BW, respectively. CONCLUSIONS: Percentiles generated are applicable in research on the relationship of the placenta with perinatal outcomes and health throughout the life cycle. PMID- 26544057 TI - [Informed concent for emergency medicine research]. AB - Discussions of consent for research in Emergency Medicine and for procedures during medical emergencies must take into account the nature of both the specialty and the patients that present to emergency departments. With this knowledge, it becomes clear that, popular misconceptions to the contrary, Emergency Medicine research plays a vital role in care, and informed consent (or waiver for minimal-risk research) remains the standard for most emergency care research. Indeed, to publish research in peer-reviewed journals requires evidence of a research ethics committee's approval, which usually means obtaining informed consent but can also include (in the United States) a waiver or intense review and ongoing oversight. Such review and oversight, termed Retrospective/Deferred Consent, is a way of permitting research without prospective informed consent in the very limited circumstances of life- or limb-threatening diseases or injuries. Research Ethics Committees only approve Retrospective/Deferred Consent when no other option exists, when clinical equipoise exists, and when they can carefully monitor the study. Research performed in such time-sensitive clinical situations, once banned as unethical, has led to vital lifesaving alterations in medical practice affecting millions of patients. PMID- 26544058 TI - [Paraneoplastic dermatomyositis related to breast cancer: rare clinical association in two patients]. AB - Paraneoplastic dermatomyositis is an inflammatory disease of the connective tissue that is caused by inmmunologic events in the presence of malignant tumors. It is more likely to happen in middle aged women and is related to ovarian, pancreatic, stomach and colon cancer and non Hogdkin lymphoma. We present two cases of dermatomyositis, with amyopathic origin associated to breast cancer. The first case occurs as the neoplasia evolves and the second one as an initial manifestation that leads to the search and subsequent diagnosis of cancer. PMID- 26544059 TI - [Chronic Duodenitis and Celiac Disease: a path between the nonspecific and the early stages of Marsh]. AB - Given the advances in diagnosis for CD, some patients are detected with symptoms and signs of food intolerance, which have positive antibodies and autoantibodies for coeliac disease, whom present proximal bowel biopsies with chronic nonspecific duodenitis and are not associated with stages 0 and 1 Marsh. On the other hand, patients with bloating, abdominal pain, pondostatural delay, negative antibodies for CD, and chronic nonspecific duodenitis in whom removing cow's milk or gluten, the symptoms remit. There are also celiac patients with biopsies before diagnosis, with chronic nonspecific duodenitis. In this paper, we summarize three brothers with different degrees of chronic duodenitis, one with chronic nonspecific duodenitis, and two with histopathological sings of coeliac disease. It is an invitation to think that chronic nonspecific duodenitis in some patients may be an earlier manifestation of celiac disease. PMID- 26544060 TI - Correction: Drosophila americana Diapausing Females Show Features Typical of Young Flies. PMID- 26544061 TI - Design of Multifunctional Liposomal Nanocarriers for Folate Receptor-Specific Intracellular Drug Delivery. AB - As a novel carrier for folate receptor (FR)-targeted intracellular delivery, we designed two types of targetable liposomal systems using Pep-1 peptide (Pep1) and folic acid as a cell-penetrating peptide (CPP) and target molecule, respectively. Folate-linked Pep1 (Fol-Pep1) was synthesized by solid phase peptide synthesis (SPPS) and verified using (1)H NMR and far-ultraviolet (UV) circular dichroism (CD). The chimeric ligand (Fol-Pep1)-modified liposome (cF-P-L) was prepared by coupling Fol-Pep1 to maleimide-derivatized liposomes at various ratios. The dual ligand (folate and Pep1)-modified liposome (dF/P-L) was prepared by separately attaching both ligands to the liposomal surface via a short (PEG2000) or long (PEG3400) linker. The physical and conformational characteristics including vesicle size, zeta potential, and the number of conjugated ligands were determined. Intracellular uptake specificities of various fluorescent probe containing cF-P-L and dF/P-L systems were assessed using FR-positive HeLa and FR negative HaCaT cells. Cellular uptake behavior was visualized by confocal laser scanning microscopy (CLSM). Internalization was time-dependent. Fol-Pep1 and Pep 1 cytotoxicities were negligible up to 25 MUM in FR-positive and FR-negative cells. Empty cF-P-L and dF/P-L were nontoxic at the concentration used. The optimized dF3/P2(450/90) system carrying 450 PEG3400-linked folate and 90 PEG2000 linked Pep1 molecules could be a good candidate for FR-specific intracellular drug delivery. PMID- 26544062 TI - Procarbazine, lomustine and vincristine or temozolomide: which is the better regimen? AB - Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring 1p19q codeletion. However, with the emergence of temozolomide as an easier to administer and less toxic alternative regimen, PCV fell out of favor. Now, long-term results of two Phase III studies conceived in the 1990s, Radiation Therapy Oncology Group (RTOG) 9402 and European Organisation for Research and Treatment of Cancer (EORTC) 26951, resurrected debate about the potential role of PCV. No adequately powered prospective trial has compared chemotherapy alone with PCV versus temozolomide for newly diagnosed 1p19q codeleted AOs. Available data suggest responses may be both more frequent and more durable with PCV, and survival may be longer. Which regimen is 'better', therefore, depends on the importance of different metrics (i.e., toxicity, complexity, efficacy), and await definitive results from the important ongoing and recently redesigned CODEL international Phase III trial. PMID- 26544063 TI - Is there a heart rate paradox in acute heart failure? AB - BACKGROUND: Higher heart rate predicts higher mortality in chronic heart failure (HF). We studied the prognostic impact of admission heart rate in acute HF and analysed the importance of its change during hospitalization. METHODS: Acute HF patients were studied. Endpoint was all-cause death. Patients were followed-up for 12 months from hospital admission. Cox-regression analysis was used to study the association of heart rate (both as a continuous and as a categorical variable) with mortality. Analysis was stratified according to admission rhythm and to systolic dysfunction. Multivariate models were built. Patients surviving hospitalization were additionally cross-classified attending to admission and discharge heart rates - cut-offs: 100 and 80 beats per minute (bpm), respectively. RESULTS: We analysed 564 patients. Median age was 78 years and median admission heart rate 87 bpm. In a 12-month period 205 patients died, 23 in hospital. Mortality increased steadily with heart rate decrease. Patients with heart rate >= 100 bpm had a multivariate-adjusted HR of 12-month death of 0.57 (95%CI: 0.39-0.81), and the HR was 0.92 (0.85-0.98) per 10 bpm increase in heart rate. Association of heart rate with mortality was stronger in patients in sinus rhythm (SR) and in those with systolic dysfunction. Eighty-seven patients had admission heart rate >= 100 and discharge heart rate < 80 bpm. In them, death rate was 14.9%; in the remaining patients it was 37.7%. CONCLUSIONS: Higher admission heart rate predicted survival advantage in acute HF. Patients presenting with tachycardia and discharged with a controlled heart rate had better outcome than those admitted non-tachycardic or discharged with a non controlled heart rate. PMID- 26544064 TI - Mobilization of stem and progenitor cells in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. PMID- 26544065 TI - Acute ischemia stroke: A rare and severe complication of ovarian hyperstimulation syndrome. PMID- 26544066 TI - Identification and Characterization of the Cyclin-Dependent Kinases Gene Family in Silkworm, Bombyx mori. AB - Cyclin-dependent protein kinases (CDKs) play key roles at different checkpoint regulations of the eukaryotic cell cycle. However, only few studies of lepidoptera CDK family proteins have been reported so far. In this study, we performed the cDNA sequencing of 10 members of the CDK family in Bombyx mori. Gene structure analysis suggested that CDK12 and CDC2L1 owned two and three isoforms, respectively. Phylogenetic analysis showed that CDK genes in different species were highly conserved, implying that they evolved independently even before the split between vertebrates and invertebrates. We found that the expression levels of BmCDKs in 13 tissues of fifth-instar day 3 larvae were different: CDK1, CDK7, and CDK9 had a high level of expression, whereas CDK4 was low-level expressed and was detected only in the testes and fat body cells. Similar expression profiles of BmCDKs during embryo development were obtained. Among the variants of CDK12, CDK12 transcript variant A had the highest expression, and the expression of CDC2L1 transcript variant A was the highest among the variants of CDC2L1. It was shown from the RNAi experiments that the silencing of CDK1, CDK10, CDK12, and CDC2L1 could influence the cells from G0/G1 to S phase transition. PMID- 26544067 TI - UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development. AB - The Ufm1 conjugation system is an ubiquitin-like modification system that consists of Ufm1, Uba5 (E1), Ufc1 (E2), and less defined E3 ligase(s) and targets. The biological importance of this system is highlighted by its essential role in embryogenesis and erythroid development, but the underlying mechanism is poorly understood. UFBP1 (Ufm1 binding protein 1, also known as DDRGK1, Dashurin and C20orf116) is a putative Ufm1 target, yet its exact physiological function and impact of its ufmylation remain largely undefined. In this study, we report that UFBP1 is indispensable for embryonic development and hematopoiesis. While germ-line deletion of UFBP1 caused defective erythroid development and embryonic lethality, somatic ablation of UFBP1 impaired adult hematopoiesis, resulting in pancytopenia and animal death. At the cellular level, UFBP1 deficiency led to elevated ER (endoplasmic reticulum) stress and activation of unfolded protein response (UPR), and consequently cell death of hematopoietic stem/progenitor cells. In addition, loss of UFBP1 suppressed expression of erythroid transcription factors GATA-1 and KLF1 and blocked erythroid differentiation from CFU-Es (colony forming unit-erythroid) to proerythroblasts. Interestingly, depletion of Uba5, a Ufm1 E1 enzyme, also caused elevation of ER stress and under expression of erythroid transcription factors in erythroleukemia K562 cells. By contrast, knockdown of ASC1, a newly identified Ufm1 target that functions as a transcriptional co-activator of hormone receptors, led to down-regulation of erythroid transcription factors, but did not elevate basal ER stress. Furthermore, we found that ASC1 was associated with the promoters of GATA-1 and Klf1 in a UFBP1-dependent manner. Taken together, our findings suggest that UFBP1, along with ASC1 and other ufmylation components, play pleiotropic roles in regulation of hematopoietic cell survival and differentiation via modulating ER homeostasis and erythroid lineage-specific gene expression. Modulating the activity of this novel ubiquitin-like system may represent a novel approach to treat blood-related diseases such as anemia. PMID- 26544069 TI - Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension. AB - BACKGROUND/AIMS: To investigaterole of serotonin (5-HT) and serotonin transporter (5-HTT) in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH) and the effect of statins on regulating 5HT and 5-HTT. METHODS: A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day. After 16 weeks of cigarette smoke exposure, body weight and mean pulmonary arterial pressure (mPAP) were measured, bronchoalveolar lavage (BAL) was performed, and lung tissues and blood samples were collected to determine cardiopulmonary pathology, physiological indices, blood levelof 5-HT and expression of 5-HTT in the lung. RESULTS: In addition to alveolar structural damage (COPD-like injury), chronic cigarette smoke exposure lead to pulmonary artery remodeling and PAH as evidenced by significant elevation of mPAP, RVHI, WT%and WA%. Cigarette smoke exposure resulted in significant reduction in animal body weight, and simvastatin significantly prevented smoke-induced weight loss. The number of inflammatory cells in BALF was dramatically increased in smoke exposed rats, and simvastatin dampened the number of leukocytes, neutrophils, lymphocytes, and macrophages. In addition, circulating 5-HTand expression of 5 HTT in the lung were significantly increased in the smoked rats compared to control rats, and it was significantly reduced by simvastatin. Alteration of BALF inflammatory cells, 5-HT and 5-HTT was significantly correlated with changes of mPAP, RVHI, WT% and WA%. CONCLUSIONS: Cigarette smoke exposure could result in not only COPD, but also PAH, which may attribute to the alteration of blood 5-HT and lung tissue 5-HTT. Simvastatin could significantly inhibited 5-HT and 5-HTT expression, and by which mechanism, it may protect animals from development of PAH. PMID- 26544070 TI - Changes and Relationships of Climatic and Hydrological Droughts in the Jialing River Basin, China. AB - The comprehensive assessment of climatic and hydrological droughts in terms of their temporal and spatial evolutions is very important for water resources management and social development in the basin scale. To study the spatial and temporal changes of climatic and hydrological droughts and the relationships between them, the SPEI and SDI are adopted to assess the changes and the correlations of climatic and hydrological droughts by selecting the Jialing River basin, China as the research area. The SPEI and SDI at different time scales are assessed both at the entire Jialing River basin and at the regional levels of the three sub basins. The results show that the SPEI and SDI are very suitable for assessing the changes and relationships of climatic and hydrological droughts in large basins. Based on the assessment, for the Jialing River basin, climatic and hydrological droughts have the increasing tendency during recent several decades, and the increasing trend of climatic droughts is significant or extremely significant in the western and northern basin, while hydrological drought has a less significant increasing trend. Additionally, climatic and hydrological droughts tend to increase in the next few years. The results also show that on short time scales, climatic droughts have one or two months lag impact on hydrological droughts in the north-west area of the basin, and have one month lag impact in south-east area of the basin. The assessment of climatic and hydrological droughts based on the SPEI and SDI could be very useful for water resources management and climate change adaptation at large basin scale. PMID- 26544068 TI - Microstructural Analysis of Peripheral Lung Tissue through CPMG Inter-Echo Time R2 Dispersion. AB - Since changes in lung microstructure are important indicators for (early stage) lung pathology, there is a need for quantifiable information of diagnostically challenging cases in a clinical setting, e.g. to evaluate early emphysematous changes in peripheral lung tissue. Considering alveoli as spherical air-spaces surrounded by a thin film of lung tissue allows deriving an expression for Carr Purcell-Meiboom-Gill transverse relaxation rates R2 with a dependence on inter echo time, local air-tissue volume fraction, diffusion coefficient and alveolar diameter, within a weak field approximation. The model relaxation rate exhibits the same hyperbolic tangent dependency as seen in the Luz-Meiboom model and limiting cases agree with Brooks et al. and Jensen et al. In addition, the model is tested against experimental data for passively deflated rat lungs: the resulting mean alveolar radius of RA = 31.46 +/- 13.15 MUm is very close to the literature value (~34 MUm). Also, modeled radii obtained from relaxometer measurements of ageing hydrogel foam (that mimics peripheral lung tissue) are in good agreement with those obtained from MUCT images of the same foam (mean relative error: 0.06 +/- 0.01). The model's ability to determine the alveolar radius and/or air volume fraction will be useful in quantifying peripheral lung microstructure. PMID- 26544071 TI - Effects of 24 CYP2D6 Variants Found in the Chinese Population on the Metabolism of Risperidone. AB - AIMS: Cytochrome P450 (CYP450) 2D6 is an important member of the P450 enzyme superfamily and responsible for clearing 25% of clinically important drugs. The aim of this study was to assess the catalytic characteristics of 24 CYP2D6 allelic isoforms found in the Chinese population and their effects on the metabolism of risperidone in vitro. METHODS: Insect microsomes expressing wild type CYP2D6 and 24 CYP2D6 allelic variants were incubated with 20-1,000 MUmol/l risperidone for 40 min at 37 degrees C. After termination, risperidone and 9-OH risperidone, the metabolite of risperidone, were precipitated and used for signal collection by ultra-performance liquid-chromatography tandem mass spectrometry. RESULTS: Among 24 CYP2D6 variants tested, 2 variants (CYP2D6*92 and CYP2D6*96) were found to be with no detectable activity. Two variants (E215K and R440C) exhibited higher intrinsic clearance values than the wild-type protein, while the remaining 20 CYP2D6 allelic variants exhibited significantly decreased clearance values (2.01-87.56%) compared to CYP2D6*1. CONCLUSION: These findings suggest that more attention should be directed to subjects carrying these infrequent CYP2D6 alleles when administering risperidone in the clinic. This is the first report of all these novel alleles for risperidone metabolism, providing fundamental data for further clinical studies on CYP2D6 alleles. PMID- 26544072 TI - Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study. AB - CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections. PMID- 26544074 TI - Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation. AB - To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27+/-0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 +/- 0.37, and elimination rate constant was 0.12 +/- 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 +/- 0.72 to 2.90 +/- 0.97 times/day, p = 0.002 and from 32.54 +/- 8.43 to 42.24 +/- 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 +/- 0.69 to 2.37 +/- 0.86 times/day, p = 0.071 and from 33.91 +/- 11.85 to 31.61 +/- 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO. PMID- 26544073 TI - In Vitro Identification of Histatin 5 Salivary Complexes. AB - With recent progress in the analysis of the salivary proteome, the number of salivary proteins identified has increased dramatically. However, the physiological functions of many of the newly discovered proteins remain unclear. Closely related to the study of a protein's function is the identification of its interaction partners. Although in saliva some proteins may act primarily as single monomeric units, a significant percentage of all salivary proteins, if not the majority, appear to act in complexes with partners to execute their diverse functions. Coimmunoprecipitation (Co-IP) and pull-down assays were used to identify the heterotypic complexes between histatin 5, a potent natural antifungal protein, and other salivary proteins in saliva. Classical protein protein interaction methods in combination with high-throughput mass spectrometric techniques were carried out. Co-IP using protein G magnetic Sepharose TM beads suspension was able to capture salivary complexes formed between histatin 5 and its salivary protein partners. Pull-down assay was used to confirm histatin 5 protein partners. A total of 52 different proteins were identified to interact with histatin 5. The present study used proteomic approaches in conjunction with classical biochemical methods to investigate protein-protein interaction in human saliva. Our study demonstrated that when histatin 5 is complexed with salivary amylase, one of the 52 proteins identified as a histatin 5 partner, the antifungal activity of histatin 5 is reduced. We expected that our proteomic approach could serve as a basis for future studies on the mechanism and structural-characterization of those salivary protein interactions to understand their clinical significance. PMID- 26544075 TI - Evaluation of Multi-tRNA Synthetase Complex by Multiple Reaction Monitoring Mass Spectrometry Coupled with Size Exclusion Chromatography. AB - Eight aminoacyl-tRNA synthetases (M, K, Q, D, R, I, EP and LARS) and three auxiliary proteins (AIMP1, 2 and 3) are known to form a multi-tRNA synthetase complex (MSC) in mammalian cells. We combined size exclusion chromatography (SEC) with reversed-phase liquid chromatography multiple reaction monitoring mass spectrometry (RPLC-MRM-MS) to characterize MSC components and free ARS proteins in human embryonic kidney (HEK 293T) cells. Crude cell extract and affinity purified proteins were fractionated by SEC in non-denaturing state and ARSs were monitored in each fraction by MRM-MS. The eleven MSC components appeared mostly in earlier SEC fractions demonstrating their participation in complex formation. TARSL2 and AIMP2-DX2, despite their low abundance, were co-purified with KARS and detected in the SEC fractions, where MSC appeared. Moreover, other large complex forming ARS proteins, such as VARS and FARS, were detected in earlier fractions. The MRM-MS results were further confirmed by western blot analysis. Our study demonstrates usefulness of combined SEC-MRM analysis for the characterization of protein complexes and in understanding the behavior of minor isoforms or variant proteins. PMID- 26544077 TI - Novel Multidisciplinary Management of a Retropharyngeal Hematoma With Pulmonary Stenting. AB - Retropharyngeal hematomas (RHs) represents a rare airway obstruction that requires timely intervention to avoid a fatal outcome. Further complicating this malady, RHs of massive proportions can complicate the decision of management selection. After comprehensive literature search, there has been no mention of pulmonary stenting as an intervention for RH. The following case presentation will demonstrate the importance of multidisciplinary management of a 60-year-old presenting with a RH causing airway obstruction, with the use of a novel approach. Airway stenting is a novel, conservative approach for successfully managing patients presenting with massive RH. PMID- 26544076 TI - Cecropins from Plutella xylostella and Their Interaction with Metarhizium anisopliae. AB - Cecropins are the most potent induced peptides to resist invading microorganisms. In the present study, two full length cDNA encoding cecropin2 (Px-cec2) and cecropin3 (Px-cec3) were obtained from P. xylostella by integrated analysis of genome and transcriptome data. qRT-PCR analysis revealed the high levels of transcripts of Px-cecs (Px-cec1, Px-cec2 and Px-cec3) in epidermis, fat body and hemocytes after 24, 30 and 36 h induction of Metarhizium anisopliae, respectively. Silencing of Spatzle and Dorsal separately caused the low expression of cecropins in the fat body, epidermis and hemocytes, and made the P.xylostella larvae more susceptible to M. anisopliae. Antimicrobial assays demonstrated that the purified recombinant cecropins, i.e., Px-cec1, Px-cec2 and Px-cec3, exerted a broad spectrum of antimicrobial activity against fungi, as well as Gram-positive and Gram-negative bacteria. Especially, Px-cecs showed higher activity against M. anisopliae than another selected fungi isolates. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that cecropins exerted the vital morphological alterations to the spores of M. anisopliae. Based on our results, cecropins played an imperative role in resisting infection of M. anisopliae, which will provide the foundation of biological control of insect pests by using cecorpins as a target in the future. PMID- 26544078 TI - Self-Powered, High-Speed and Visible-Near Infrared Response of MoO(3-x)/n-Si Heterojunction Photodetector with Enhanced Performance by Interfacial Engineering. AB - Photodetectors with a wide spectrum response are important components for sensing, imaging, and other optoelectronic applications. A molybdenum oxide (MoO(3-x))/Si heterojunction has been applied as solar cells with great success, but its potential in photodetectors has not been explored yet. Herein, a self powered, high-speed heterojunction photodetector fabricated by coating an n-type Si hierarchical structure with an ultrathin hole-selective layer of molybdenum oxide (MoO(3-x)) is first investigated. Excellent and stable photoresponse performance is obtained by using a methyl group passivated interface. The heterojunction photodetector demonstrated high sensitivity to a wide spectrum from 300 to 1100 nm. The self-powered photodetector shows a high detectivity of (~6.29 * 10(12) cmHz(1/2) W(-1)) and fast response time (1.0 MUs). The excellent photodetecting performance is attributed to the enhanced interfacial barrier height and three-dimensional geometry of Si nanostructures, which is beneficial for efficient photocarrier collection and transportation. Finally, our devices show excellent long-term stability in air for 6 months with negligible performance degradation. The thermal evaporation method for large-scale fabrication of MoO(3-x)/n-Si photodetectors makes it suitable for self-powered, multispectral, and high-speed response photodetecting applications. PMID- 26544079 TI - Reduction of the number of fetuses for women with a multiple pregnancy. AB - BACKGROUND: When couples are faced with the dilemma of a higher-order multiple pregnancy there are three options. Termination of the entire pregnancy has generally not been acceptable to women, especially for those with a past history of infertility. Attempting to continue with all the fetuses is associated with inherent problems of preterm birth, survival and long-term morbidity. The other alternative relates to reduction in the number of fetuses by selective termination. The acceptability of these options for the couple will depend on their social background and underlying beliefs. This review focused on reduction in the number of fetuses. OBJECTIVES: To assess a policy of multifetal reduction with a policy of expectant management of women with a multiple pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015). SELECTION CRITERIA: Randomised controlled trials with reported data that compared outcomes in mothers and babies who were managed expectantly with outcomes in women who underwent selective fetal reduction of a multiple pregnancy. DATA COLLECTION AND ANALYSIS: We planned that two review authors would independently assess trials for inclusion and risk of bias, extract data and check them for accuracy. However, no randomised trials were identified. MAIN RESULTS: There were no randomised controlled trials identified. AUTHORS' CONCLUSIONS: We found no available data from randomised trials to inform the risks and benefits of pregnancy reduction procedures for women with a multiple pregnancy. While randomised controlled trials will provide the most reliable evidence about the risks and benefits of fetal reduction procedures, reduction in the number of fetuses by selective termination may not be acceptable to women, particularly couples with a past history of infertility. The acceptability of this option, and willingness to undergo randomisation will depend on the couple's social background and beliefs, and consequently, recruitment to such a trial may prove exceptionally difficult. PMID- 26544080 TI - Reevaluating the weekend effect on patients with hydrocephalus undergoing operative shunt intervention. AB - OBJECT Recently published data have suggested an increase in adverse outcomes in pediatric patients after insertion or revision of a ventricular CSF diversion shunt after a same-day weekend procedure. The authors undertook an evaluation of the impact of weekend admission and time to shunting on surgery-related quality outcomes in pediatric patients who underwent ventricular shunt insertion or revision. METHODS Pediatric patients with hydrocephalus who underwent ventriculoperitoneal, ventriculoatrial, or ventriculopleural shunt placement were selected from the 2000-2010 Nationwide Inpatient Sample and Kids' Inpatient Database. Multivariate regression analyses (adjusted for patient, hospital, case severity, and time to shunting) were used to determine the differences in inpatient mortality and routine discharge rates among patients admitted on a weekday versus those among patients admitted on a weekend. RESULTS There were 99,472 pediatric patients with shunted hydrocephalus, 16% of whom were admitted on a weekend. After adjustment for disease severity, time to procedure, and admission acuity, weekend admission was not associated with an increase in the inpatient mortality rate (p = 0.46) or a change in the percentage of routine discharges (p = 0.98) after ventricular shunt procedures. In addition, associations were unchanged after an evaluation of patients who underwent shunt revision surgery. High-volume centers were incidentally noted in multivariate analysis to have increased rates of routine discharge (OR 1.04 [95% CI 1.01 1.07]; p = 0.02). CONCLUSIONS Contrary to those of previous studies, the authors' data suggest that weekend admission is not associated with poorer outcomes for ventricular shunt insertion or revision. Increased rates of routine discharge were noted at high-volume centers. PMID- 26544081 TI - Pediatric skull base reconstruction: case report of a tunneled temporoparietal fascia flap. AB - The authors of this report present a pediatric case involving the use of a tunneled temporoparietal fascia flap to reconstruct a skull base defect for a multiply recurrent clival chordoma and cerebrospinal fluid leak, demonstrate the surgical technique through illustrations and intraoperative photos, and review the pertinent literature. A 9-year-old female patient underwent extensive clival chordoma resection via both the endoscopic and open approaches, which ultimately exhausted the bilateral nasoseptal flaps and other intranasal reconstructive options. Following proton beam radiation and initiation of chemotherapy, tumor recurrence was managed with further endoscopic resection, which was complicated by a recalcitrant cerebrospinal fluid leak. A tunneled temporoparietal fascia flap was used to provide vascular tissue to augment an endoscopic repair of the leak and reconstruction of the skull base. While the nasoseptal flap remains the workhorse for many pediatric and adult endoscopic skull base reconstructions, the tunneled temporoparietal fascia flap has a demonstrated efficacy in adults when the nasoseptal flap and other intranasal flaps are unavailable. This report documents a pediatric case, serving as a step toward establishing this technique in the pediatric population. PMID- 26544082 TI - Editorial: Predicting shunt failure in children. PMID- 26544083 TI - Predicting shunt failure in children: should the global shunt revision rate be a quality measure? AB - OBJECT: Ventricular shunts for pediatric hydrocephalus continue to be plagued with high failure rates. Reported risk factors for shunt failure are inconsistent and controversial. The raw or global shunt revision rate has been the foundation of several proposed quality metrics. The authors undertook this study to determine risk factors for shunt revision within their own patient population. METHODS: In this single-center retrospective cohort study, a database was created of all ventricular shunt operations performed at the authors' institution from January 1, 2010, through December 2013. For each index shunt surgery, demographic, clinical, and procedural variables were assembled. An "index surgery" was defined as implantation of a new shunt or the revision or augmentation of an existing shunt system. Bivariate analyses were first performed to evaluate individual effects of each independent variable on shunt failure at 90 days and at 180 days. A final multivariate model was chosen for each outcome by using a backward model selection approach. RESULTS: There were 466 patients in the study accounting for 739 unique ("index") operations, for an average of 1.59 procedures per patient. The median age for the cohort at the time of the first shunt surgery was 5 years (range 0-35.7 years), with 53.9% males. The 90- and 180 day shunt failure rates were 24.1% and 29.9%, respectively. The authors found no variable-demographic, clinical, or procedural-that predicted shunt failure within 90 or 180 days. CONCLUSIONS: In this study, none of the risk factors that were examined were statistically significant in determining shunt failure within 90 or 180 days. Given the negative findings and the fact that all other risk factors for shunt failure that have been proposed in the literature thus far are beyond the control of the surgeon (i.e., nonmodifiable), the use of an institution's or individual's global shunt revision rate remains questionable and needs further evaluation before being accepted as a quality metric. PMID- 26544084 TI - Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. AB - OBJECT Even with improved prenatal and neonatal care, intraventricular hemorrhage (IVH) occurs in approximately 25%-30% of preterm infants, with a subset of these patients developing hydrocephalus. This study was undertaken to describe current trends in hospitalization of preterm infants with posthemorrhagic hydrocephalus (PHH) using the Nationwide Inpatient Sample (NIS) and the Kids' Inpatient Database (KID). METHODS The KID and NIS were combined to generate data for the years 2000-2010. All neonatal discharges with ICD-9-CM codes for preterm birth with IVH alone or with IVH and hydrocephalus were included. RESULTS There were 147,823 preterm neonates with IVH, and 9% of this group developed hydrocephalus during the same admission. Of patients with Grade 3 and 4 IVH, 25% and 28%, respectively, developed hydrocephalus in comparison with 1% and 4% of patients with Grade 1 and 2 IVH, respectively. Thirty-eight percent of patients with PHH had permanent ventricular shunts inserted. Mortality rates were 4%, 10%, 18%, and 40%, respectively, for Grade 1, 2, 3, and 4 IVH during initial hospitalization. Length of stay has been trending upward for both groups of IVH (49 days in 2000, 56 days in 2010) and PHH (59 days in 2000, 70 days in 2010). The average hospital cost per patient (adjusted for inflation) has also increased, from $201,578 to $353,554 (for IVH) and $260,077 to $495,697 (for PHH) over 11 years. CONCLUSIONS The number of neonates admitted with IVH has increased despite a decrease in the number of preterm births. Rates of hydrocephalus and mortality correlated closely with IVH grade. The incidence of hydrocephalus in preterm infants with IVH remained stable between 8% and 10%. Over an 11-year period, there was a progressive increase in hospital cost and length of stay for preterm neonates with IVH and PHH that may be explained by a concurrent increase in the proportion of patients with congenital cardiac anomalies. PMID- 26544085 TI - WITHDRAWN: Intravesical Bacillus Calmette-Guerin versus mitomycin C for Ta and T I bladder cancer. PMID- 26544086 TI - Notice of Retraction: Ramipril Markedly Improves Walking Ability in Patients With Peripheral Arterial Disease. PMID- 26544087 TI - Two Types of Water at the Water-Surfactant Interface Revealed by Time-Resolved Vibrational Spectroscopy. AB - The surfactant sodium dodecyl sulfate (SDS) is widely used as a detergent for both domestic and industrial applications. It forms a self-assembled monolayer on the surface of water. We report a microscopic model for the interaction between the surfactant and water and between water molecules at the interface, revealed using static and time-resolved two-dimensional sum frequency generation spectroscopy. Two distinct subensembles of water in the presence of this negatively charged SDS surfactant have been identified: those close to the SDS headgroup having fairly isolated O-H groups, i.e., localized O-H stretch vibrations, and those whose O-H stretch vibrations are delocalized, i.e., shared between multiple O-H bonds. The two subensembles are coupled, with subpicosecond energy transfer occurring between them. This is markedly different from O-H bonds at the air-water interface, which are less heterogeneous, and indicates that the water molecules that interact with the surfactant headgroups have hydrogen bonding properties different from those of water molecules interacting with the other water molecules. PMID- 26544088 TI - Homology Model-Based Virtual Screening for the Identification of Human Helicase DDX3 Inhibitors. AB - Targeting cellular cofactors instead of viral enzymes represents a new strategy to combat infectious diseases, which should help to overcome the problem of viral resistance. Recently, it has been revealed that the cellular ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3) is an essential host factor for the replication of several viruses such as HIV, HCV, JEV, Dengue, and West Nile. Accordingly, a drug targeting DDX3 could theoretically inhibit all viruses that are dependent on this host factor. Herein, for the first time, a model of hDDX3 in its closed conformation, which binds the viral RNA was developed by using the homology module of Prime through the Maestro interface of Schrodinger. Next, a structure-based virtual screening protocol was applied to identify DDX3 small molecule inhibitors targeting the RNA binding pocket. As a result, an impressive hit rate of 40% was obtained with the identification of 10 active compounds out of the 25 tested small molecules. The best poses of the active ligands highlighted the crucial residues to be targeted for the inhibition of the helicase activity of DDX3. The obtained results confirm the reliability of the constructed DDX3/RNA model and the proposed computational strategy for investigating novel DDX3 inhibitors. PMID- 26544089 TI - Potentiation Effects of Half-Squats Performed in a Ballistic or Nonballistic Manner. AB - This study examined and compared the acute effects of ballistic and nonballistic concentric-only half-squats (COHSs) on squat jump performance. Fifteen resistance trained men performed a squat jump 2 minutes after a control protocol or 2 COHSs at 90% of their 1 repetition maximum (1RM) COHS performed in a ballistic or nonballistic manner. Jump height (JH), peak power (PP), and allometrically scaled peak power (PPa) were compared using three 3 * 2 repeated-measures analyses of variance. Statistically significant condition * time interaction effects existed for JH (p = 0.037), PP (p = 0.041), and PPa (p = 0.031). Post hoc analysis revealed that the ballistic condition produced statistically greater JH (p = 0.017 and p = 0.036), PP (p = 0.031 and p = 0.026), and PPa (p = 0.024 and p = 0.023) than the control and nonballistic conditions, respectively. Small effect sizes for JH, PP, and PPa existed during the ballistic condition (d = 0.28-0.44), whereas trivial effect sizes existed during the control (d = 0.0-0.18) and nonballistic (d = 0.0-0.17) conditions. Large statistically significant relationships existed between the JH potentiation response and the subject's relative back squat 1RM (r = 0.520; p = 0.047) and relative COHS 1RM (r = 0.569; p = 0.027) during the ballistic condition. In addition, large statistically significant relationship existed between JH potentiation response and the subject's relative back squat strength (r = 0.633; p = 0.011), whereas the moderate relationship with the subject's relative COHS strength trended toward significance (r = 0.483; p = 0.068). Ballistic COHS produced superior potentiation effects compared with COHS performed in a nonballistic manner. Relative strength may contribute to the elicited potentiation response after ballistic and nonballistic COHS. PMID- 26544090 TI - Postpartum Teenagers' Views on Providing Contraception in School-Based Health Clinics. AB - BACKGROUND: To determine characteristics of teen pregnancies in southeast Texas and the opinions of postpartum teenagers with regard to having contraceptive services available in high school clinics. METHODS: A cross-sectional study of postpartum teenagers interviewed during their hospital stay. RESULTS: Of 404 postpartum teenagers interviewed, 86% had unplanned pregnancies. Approximately 53% of respondents first had intercourse at less than 16 years of age. Of the 130 teenagers who had used contraception prior to pregnancy, 85% became pregnant because they were unable to visit the clinic to obtain a contraceptive refill or replacement. In multivariate modeling, factors associated with using contraceptives prior to pregnancy included black race (p < .001) and more than 1 previous pregnancy (p < .001). Variables associated with having an unplanned pregnancy included having discussed contraceptives at home or school (p = 0.049). Of the 404 postpartum teenagers surveyed, 223 (82%) were in favor of having contraceptive services offered in high school clinics. CONCLUSIONS: Contraceptive education is not sufficient to prevent teenage pregnancy. Increase in access is critical as teenagers with previous pregnancies were more likely to use contraception, likely due to their interaction with the medical community during the antecedent pregnancy. One possible solution is to bring contraceptive services to the teenagers, by offering them at school based health systems. A majority of teenagers surveyed in this study supported this proposal. PMID- 26544091 TI - Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review. AB - LEARNING OBJECTIVES: After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. ABSTRACT: Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating behaviors, mental and physical health, family interactions, and child growth patterns. PMID- 26544092 TI - Virginia Tech as a Sentinel Event: The Role of Psychiatry in Managing Emotionally Troubled Students on College and University Campuses. AB - This article reviews the role of psychiatry in colleges and universities, and argues that psychiatrists are significantly underutilized as consultants and educators in managing emotionally troubled students. Focusing on the 2007 Virginia Tech mass shooting case as a sentinel event, the article outlines mental health issues facing post-secondary institutions and legal issues related to psychiatric services, including the following: the increased need for psychiatric services on campus; communication challenges among campus groups involved in managing high-risk students; efforts to balance patient confidentiality with public safety; confusion over privacy laws; and the changing role of the campus psychiatrist. An important conclusion is that psychiatrists working in campus settings have distinctive, vital skill sets that enable them to go far beyond their traditional roles of psychiatric evaluation and treatment and to serve in critical leadership, educational, and consultative capacities to benefit both emotionally troubled students and the wider campus community. PMID- 26544093 TI - Consumer Information and Treatment Resources for Posttraumatic Stress Disorder: Within Reach but Not Grasp. AB - In the context of multiple treatment options for posttraumatic stress disorder (PTSD) and a large, growing need for consumer information regarding accessible and effective treatments, this article identifies and reviews available information and treatment resources. Multiple search strategies identified a suite of information sources, including meta-analyses and systematic reviews of PTSD treatments, the program evaluation and implementation literature, the economics literature, Internet sites, and other resources for veteran and civilian consumers. Resources were evaluated with regard to their target audiences, depth and breadth of treatment options covered, nature of the information provided, and accessibility to consumers. A large body of research covers the various treatments and sets of treatment guidelines for PTSD. Despite the extensive scientific information targeted at providers and researchers, the quality, accessibility, and usability of the published research varies widely. The Veterans Health Administration provides the most extensive information on various treatment options and where to obtain treatment within that system. Publicly available websites provide information on multiple treatment options, but information to help nonveterans navigate treatment choices is limited. Published reports of PTSD program-evaluation and implementation studies are sparse. Information on PTSD treatment options available to consumers can be overwhelming and confusing, which places an unnecessary burden on an already vulnerable group of patients and their families. Exacerbating the situation is the shortage of program-evaluation and implementation research. The dearth of centralized and accessible information related to nonveteran PTSD patient groups needs to be addressed. PMID- 26544094 TI - Analysis of cytotoxicity and genotoxicity on E. coli, human blood cells and Allium cepa suggests a greater toxic potential of hair dye. AB - Pharmaceuticals and personal care products (PPCPs) are among the most important emerging environmental contaminants in recent time. PPCPs include wide range of cosmetics, among which hair dyes, are immensely popular in modern society. However, impact of hair dye and its residual discharged to the environment in relation to human health and ecological imbalance have not been widely studied. Based on the result of initial survey among the group of populations of eastern India, three most popular and commonly used permanent hair dyes are selected. Working sample of dye is prepared as recommended on the instructions booklet of the hair dye. The effect of three dyes is studied on Escherichia coli, human red blood cells (RBC), white blood cells (WBC) and Allium cepa bulbs by growth inhibition, hemolysis, 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and A. cepa micronuclei assays respectively. The Lethal dose (LD) demonstrated significant differences among three dyes and the model systems. In vitro hemolytic assays performed on RBC, and MTT assays on WBC show the cytotoxic effects of hair dye. Significant growth inhibition of E. coli has also been noted. In addition, the root tips of A. cepa treated with the dye have shown major chromosomal abnormalities coupled with cell division retardation. Here low mitotic index confirm cell division retardation. Finally, results of in vitro studies of dye-DNA interactions demonstrate electrostatic interaction. Combing all these results it confirms that hair dyes are cytotoxic and may cause mutagenic effect on living cells irrespective of microbes, plant and animal system. PMID- 26544095 TI - Correlation of spleen metabolism assessed by 18F-FDG PET with serum interleukin-2 receptor levels and other biomarkers in patients with untreated sarcoidosis. AB - BACKGROUND: The objective of our study was to assess the possible relationship between splenic F-18-fluorodeoxyglucose (18F-FDG) uptake and other established biochemical markers of sarcoidosis activity. PATIENTS AND METHODS: Thirty treatment-naive sarcoidosis patients were prospectively enrolled in this study. They underwent biochemical laboratory tests, including serum interleukin-2 receptor (sIL-2R), serum C-reactive protein, serum angiotensin-I converting enzyme, and 24-h urine calcium levels, and a whole-body combined 18F-FDG PET/computed tomography (PET/CT) scan as a part of an ongoing study at our institute. These biomarkers were statistically compared in these patients. RESULTS: A statistically significant linear dependence was detected between sIL 2R and log-transformed spleen-average standard uptake value (SUV avg) (R2=0.488, P<0.0001) and log-transformed spleen-maximum standard uptake value (SUV max) (R2=0.490, P<0.0001). sIL-2R levels and splenic size correlated linearly (Pearson's r=0.373, P=0.042). Multivariate linear regression analysis revealed that this correlation remained significant after age and sex adjustment (beta=0.001, SE=0.001, P=0.024). No statistically significant associations were detected between (a) any two serum biomarkers or (b) between spleen-SUV measurements and any serum biomarker other than sIL-2R. CONCLUSION: Our analysis revealed an association between sIL-2R levels and spleen 18F-FDG uptake and size, whereas all other serum biomarkers were not significantly associated with each other or with PET 18F-FDG uptake. Our results suggest that splenic inflammation may be related to the systemic inflammatory response in sarcoidosis that may be associated with elevated sIL-2R levels. PMID- 26544096 TI - Is there a correlation between planar scintigraphy after 99mTc-MAA and 90Y administration? PMID- 26544097 TI - Efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography as a predictor of response in locally advanced non-small-cell carcinoma of the lung. AB - OBJECTIVE: The study assessed the role of (18)F-fluorodeoxyglucose ((18)F-FDG) Positron emission tomography (PET)/computed tomography (CT) in evaluating the prognostic value of metabolic response for progression-free survival (PFS) and overall survival (OS) in patients with locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients with locally advanced NSCLC were enrolled in this prospective study and randomly allocated to one of two treatment arms. Arm A (n=15) received two cycles of neoadjuvant chemotherapy [paclitaxel (200 mg/m(2)) and carboplatin (AUC5)] and external beam radiotherapy (60 Gy/30 fractions/6 weeks). Arm B (n=15) received the same neoadjuvant chemotherapy followed by external beam radiotherapy (48 Gy/20 fractions/4 weeks) with concomitant cisplatin 30 mg/m(2) weekly. Patients underwent (18)F-FDG PET/CT at baseline and after 6 weeks of completion of intended treatment. Pretreatment and post-treatment maximum standardized uptake values (SUVmax) were noted. Patients with a reduction of SUVmax more than 50% were considered to be metabolic responders and those with a reduction 50% or less as nonresponders. Median follow up was 18.98 months. RESULTS: Twenty-one patients completed the intended treatment. The median pretreatment and post-treatment SUVmax values were 14 and 6.4 for arm A and 15.3 and 3.5 for arm B, respectively. Significant decrease in SUVmax was observed in both arms. Metabolic response in arm A and arm B was 50 and 64%, respectively. The median PFS and OS of the responders were 22.31 and 24.73 months and those for nonresponders were 7.83 and 8.26 months, respectively. No significant difference in OS and PFS was observed between responders and nonresponders in the two arms. CONCLUSION: PET/CT distinguishes responders from nonresponders early after completion of chemoradiation in patients with locally advanced NSCLC, but did not provide any prognostic significance. PMID- 26544098 TI - Mild-to-moderate hyperglycemia will not decrease the sensitivity of 18F-FDG PET imaging in the detection of pedal osteomyelitis in diabetic patients. AB - PURPOSE: Pedal osteomyelitis is a worrisome complication of diabetic foot disease. Controlling serum glucose levels is difficult for many diabetic patients. High serum glucose levels could potentially affect the results of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging in the detection of osteomyelitis. The aim of this investigation was to determine whether high serum glucose levels diminish the diagnostic accuracy of 18F-FDG PET imaging in detecting pedal osteomyelitis in diabetic patients. MATERIALS AND METHODS: Forty eight consecutive diabetic patients with a suspicion of pedal osteomyelitis were included in this investigation. At the time of 18F-FDG administration, 21 patients had serum glucose levels less than 150 mg/dl (group A), and 27 had serum glucose levels greater than 150 mg/dl (group B). Results of PET imaging were compared with final diagnostic outcome based on histopathology and/or 12 months' clinical follow-up. RESULTS: Osteomyelitis was confirmed in 17 patients. 18F-FDG PET correctly detected osteomyelitis in 15 of 17 patients for a sensitivity of 88.3% (15/17). This technique successfully excluded osteomyelitis in 30 of 31 cases for a specificity of 96.8% (30/31) and an overall accuracy of 93.8% (45/48). The sensitivity of 18F-FDG PET imaging was 87.5% (7/8) in patients with serum glucose levels less than 150 mg/dl (group A) and 88.9% (8/9) in patients with serum glucose levels greater than 150 mg/dl (group B). These results do not significantly differ from the overall sensitivity of 88.3% (15/17). CONCLUSION: Mildly to moderately elevated serum glucose levels do not adversely affect the accuracy of 18F-FDG PET imaging in the detection of pedal osteomyelitis in diabetic patients. PMID- 26544099 TI - A Wearable All-Solid Photovoltaic Textile. AB - A solution is developed to power portable electronics in a wearable manner by fabricating an all-solid photovoltaic textile. In a similar way to plants absorbing solar energy for photosynthesis, humans can wear the as-fabricated photovoltaic textile to harness solar energy for powering small electronic devices. PMID- 26544100 TI - Increased mercury release from dental amalgam restorations after exposure to electromagnetic fields as a potential hazard for hypersensitive people and pregnant women. AB - Over the past decades, the use of common sources of electromagnetic fields such as Wi-Fi routers and mobile phones has been increased enormously all over the world. There is ongoing concern that exposure to electromagnetic fields can lead to adverse health effects. It has recently been shown that even low doses of mercury are capable of causing toxicity. Therefore, efforts are initiated to phase down or eliminate the use of mercury amalgam in dental restorations. Increased release of mercury from dental amalgam restorations after exposure to electromagnetic fields such as those generated by MRI and mobile phones has been reported by our team and other researchers. We have recently shown that some of the papers which reported no increased release of mercury after MRI, may have some methodological errors. Although it was previously believed that the amount of mercury released from dental amalgam cannot be hazardous, new findings indicate that mercury, even at low doses, may cause toxicity. Based on recent epidemiological findings, it can be claimed that the safety of mercury released from dental amalgam fillings is questionable. Therefore, as some individuals tend to be hypersensitive to the toxic effects of mercury, regulatory authorities should re-assess the safety of exposure to electromagnetic fields in individuals with amalgam restorations. On the other hand, we have reported that increased mercury release after exposure to electromagnetic fields may be risky for the pregnant women. It is worth mentioning that as a strong positive correlation between maternal and cord blood mercury levels has been found in some studies, our findings regarding the effect of exposure to electromagnetic fields on the release of mercury from dental amalgam fillings lead us to this conclusion that pregnant women with dental amalgam fillings should limit their exposure to electromagnetic fields to prevent toxic effects of mercury in their fetuses. Based on these findings, as infants and children are more vulnerable to mercury exposures, and as some individuals are routinely exposed to different sources of electromagnetic fields, we possibly need a paradigm shift in evaluating the health effects of amalgam fillings. PMID- 26544101 TI - Phosphene perception is due to the ultra-weak photon emission produced in various parts of the visual system: glutamate in the focus. AB - Phosphenes are experienced sensations of light, when there is no light causing them. The physiological processes underlying this phenomenon are still not well understood. Previously, we proposed a novel biopsychophysical approach concerning the cause of phosphenes based on the assumption that cellular endogenous ultra weak photon emission (UPE) is the biophysical cause leading to the sensation of phosphenes. Briefly summarized, the visual sensation of light (phosphenes) is likely to be due to the inherent perception of UPE of cells in the visual system. If the intensity of spontaneous or induced photon emission of cells in the visual system exceeds a distinct threshold, it is hypothesized that it can become a conscious light sensation. Discussing several new and previous experiments, we point out that the UPE theory of phosphenes should be really considered as a scientifically appropriate and provable mechanism to explain the physiological basis of phosphenes. In the present paper, we also present our idea that some experiments may support that the cortical phosphene lights are due to the glutamate-related excess UPE in the occipital cortex. PMID- 26544102 TI - Semi-purification procedures of prions from a prion-infected brain using sucrose has no influence on the nonenzymatic glycation of the disease-associated prion isoform. AB - Previous studies have shown that the Nepsilon-carboxymethyl group is linked to not only one or more N-terminal Lys residues but also to one or more Lys residues of the protease-resistant core region of the pathogenic prion isoform (PrPSc) in prion-infected brains. Using an anti-advanced glycation end product (AGE) antibody, we detected nonenzymatically glycated PrPSc (AGE-PrPSc) in prion infected brains following concentration by a series of ultracentrifugation steps with a sucrose cushion. In the present study, the levels of in vitro nonenzymatic glycation of PrPSc using sucrose were investigated to determine whether sucrose cushion can artificially and nonenzymatically induce in vitro glycation during ultracentrifugation. The first insoluble pellet fraction following the first ultracentrifugation (PU1st) collected from 263K scrapie-infected brains was incubated with sucrose, glucose or colloidal silica coated with polyvinylpyrrolidone (percoll). None of the compounds in vitro resulted in AGE PrPSc. Nonetheless, glucose and percoll produced AGEs in vitro from other proteins within PU1st of the infected brains. This reaction could lead to the AGE modified polymer(s) of nonenzymatic glycation-prone protein(s). This study showed that PrPSc is not nonenzymatically glycated in vitro with sucrose, glucose or percoll and that AGE-modified PrPSc can be isolated and enriched from prion infected brains. PMID- 26544103 TI - Oxidative damage and the pathogenesis of menopause related disturbances and diseases. AB - The postmenopausal phase of life is frequently associated in women with subjective symptoms (e.g. vasomotor) and real diseases (atherosclerosis with coronary ischemia, osteoporosis, Alzheimer-type neurodegeneration, urogenital dystrophy), which together determine the post-menopausal syndrome. Observations that oxidative damage by reactive oxygen/nitrogen species in experimental models can contribute to the pathogenesis of these disturbances stimulated research on the relationships between menopause, its endocrine deficiency, oxidative balance and the "wellness" in postmenopausal life. The connection among these events is probably due to the loss of protective actions exerted by estrogens during the fertile life. Most recent studies have revealed that estrogens exert an antioxidant action not by direct chemical neutralization of reactants as it was expected until recently but by modulating the expression of antioxidant enzymes that control levels of biological reducing agents. Also nutritional antioxidants apparently act by a similar mechanism. From this perspective it is conceivable that a cumulative control of body oxidant challenges and biological defenses could help in monitoring between "normal" and "pathological" menopause. However, as clinical studies failed to confirm this scenario in vivo, we have decided to review the existing literature to understand the causes of this discrepancy and whether this was due to methodologic reasons or to real failure of the basic hypothesis. PMID- 26544104 TI - Clinical relevance of sST2 in cardiac diseases. AB - ST2 has two main isoforms, ST2L and soluble isoform of ST2 (sST2), by alternative splicing. The interaction between interleukin (IL)-33 and the transmembrane isoform ST2L is up-regulated in response to myocardial stress and exerts cardio protective actions in the myocardium by reducing fibrosis, hypertrophy and enhancing survival. The circulating isoform sST2, by sequestering IL-33, abrogates these favorable actions and will be elevated as a maladaptive response to cardiac diseases. Indeed, circulating sST2 concentrations correlate with a worse phenotype of disease including adverse remodeling and fibrosis, cardiac dysfunction, impaired hemodynamics and higher risk of progression. In patients with acute and chronic heart failure, sST2 concentrations are strongly predictive of death, regardless of the cause and left ventricle (LV) ejection fraction, and contribute relevant information in addition to other prognosticators and biomarkers, as natriuretic peptides or troponins. sST2 also retains prognostic information in the setting of acute myocardial infarction (AMI) and predicts cardiovascular death and risk of heart failure (HF) development in these patients. sST2 could also be a promising tool to stratify the risk of sudden cardiac death (SCD) in patients with depressed LV ejection fraction. Therefore, sST2 represents a clinically relevant biomarker reflecting pathophysiological processes and contributing predictive information in the setting of several cardiovascular diseases, and especially in patients with HF. PMID- 26544105 TI - First trimester PAPP-A2, PAPP-A and hCGbeta in small-for-gestational-age pregnancies. AB - BACKGROUND: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a recently discovered protease that cleaves a subset of insulin-like growth factor binding proteins (IGFBP). The molecular function suggests its involvement in the IGF system that is vital for fetal growth and development. Our objectives were to establish first trimester median curves of PAPP-A2, PAPP-A and hCGbeta for singleton normal pregnancies and to investigate whether an altered level of one or more of the biomarkers is associated with small-for-gestational-age (SGA) neonates before and after stratification according to maternal hypertension and/or proteinuria. METHODS: This was a case-control study based on 985 pregnant women delivering normal-weighted neonates and 170 pregnant women delivering SGA neonates. PAPP-A2 was measured by ELISA. PAPP-A and hCGbeta were measured by an automatic analyzer. Median curves from 8+1 to 14+0 were established and all concentration values were converted to multiples of the median (MoM) values. RESULTS: Before stratification the SGA cases had unaffected PAPP-A2 MoM and hCGbeta MoM levels but lower PAPP-A MoM compared with normal controls. After stratification the SGA normotensive subgroup had lower PAPP-A2 MoM and PAPP-A MoM levels than the normal normotensive subgroup. Severe preeclamptic women delivering SGA neonates had higher PAPP-A2 MoM compared to the normotensive women delivering SGA neonates. CONCLUSIONS: Pregnant women delivering SGA neonates did not have altered levels of PAPP-A2 or hCGbeta but had lower PAPP-A level in the first trimester compared with pregnant women delivering normal-weighted neonates. Pregnancies complicated with severe preeclampsia and SGA may be associated with high PAPP-A2 level. PMID- 26544106 TI - Student Perceptions of Quality and Safety Competencies. AB - AIM/PURPOSE: The purpose of the study was to evaluate senior students' level of preparedness to perform and perceived importance of 22 QSEN-related skills over a three year project period. BACKGROUND: The national Quality and Safety Education in Nursing (QSEN) project promotes student learning in the provision of safe, quality health care. One Midwestern nursing program attempted to address health care challenges by purposefully utilizing the QSEN competencies for curricular changes. METHODS: This study collected data from students in their final semester of a baccalaureate program using the QSEN Student Evaluation Survey. RESULTS/FINDINGS: Students reported they were somewhat prepared to perform skills related to all six QSEN competencies. Students perceived all QSEN related skills as being as least somewhat important. CONCLUSIONS: As a result of this study, the nursing program identified areas to be developed for further growth and utilized findings to aid in curriculum revision. PMID- 26544107 TI - On the validity of within-nuclear-family genetic association analysis in samples of extended families. AB - Splitting extended families into their component nuclear families to apply a genetic association method designed for nuclear families is a widespread practice in familial genetic studies. Dependence among genotypes and phenotypes of nuclear families from the same extended family arises because of genetic linkage of the tested marker with a risk variant or because of familial specificity of genetic effects due to gene-environment interaction. This raises concerns about the validity of inference conducted under the assumption of independence of the nuclear families. We indeed prove theoretically that, in a conditional logistic regression analysis applicable to disease cases and their genotyped parents, the naive model-based estimator of the variance of the coefficient estimates underestimates the true variance. However, simulations with realistic effect sizes of risk variants and variation of this effect from family to family reveal that the underestimation is negligible. The simulations also show the greater efficiency of the model-based variance estimator compared to a robust empirical estimator. Our recommendation is therefore, to use the model-based estimator of variance for inference on effects of genetic variants. PMID- 26544108 TI - Three, two, one... TROPHO-BLAST OFF! AB - Trophoblast stem cells (TSCs) are derived from the early mouse embryo and can substantially contribute to placental development. Two studies by Kubaczka et al. (2015) and Benchetrit et al. (2015) in this issue of Cell Stem Cell now report reprogramming mouse fibroblasts into TSCs, surmounting the first lineage barrier established in development and providing new tools for researching placental specification and diseases. PMID- 26544109 TI - Imported Stem Cells Strike against Stroke. AB - Cells with neural stem cell (NSC)-like properties can be isolated from the cortex of adult brains following injury, but their origins and function are unclear. Now in Cell Stem Cell, Faiz et al. (2015) show that subventricular-zone-derived NSCs home to injured cortical area following stroke, where they generate reactive astrocytes. PMID- 26544110 TI - AMPK Keeps Tumor Cells from Starving to Death. AB - In this issue of Cell Stem Cell, Saito et al. (2015) examine how leukemia initiating cells react to metabolic stress imposed by different tissue environments. They find that inhibition of the metabolic stress sensor AMP activated protein kinase (AMPK) led to deranged glucose metabolism and redox homeostasis, resulting in reduced leukemic progression that was further attenuated by dietary restriction. PMID- 26544111 TI - The Hedgehog Hold on Homeostasis. AB - The adult lung is largely quiescent, with airway epithelia turning over slowly. Peng et al. (2015) describe a key role for the Hedgehog pathway in actively maintaining this quiescence, a surprising turn of events given the pathway's established mitogenic role, and they show that Hedgehog pathway attenuation is required for proliferative regeneration. PMID- 26544112 TI - Recent Court Ruling in Japan Exemplifies Another Layer of Regulation for Regenerative Therapy. PMID- 26544113 TI - Dynamic Pluripotent Stem Cell States and Their Applications. AB - Embryonic pluripotency can be recapitulated in vitro by a spectrum of pluripotent stem cell states stabilized with different culture conditions. Their distinct spatiotemporal characteristics provide an unprecedented tool for the study of early human development. The newly unveiled ability of some stem cell types for crossing xeno-barriers will facilitate the generation of interspecies chimeric embryos from distant species, including humans. When combined with efficient zygote genome editing technologies, xenogeneic human pluripotent stem cells may also open new frontiers for regenerative medicine applications, including the possibility of generating human organs in animals via interspecies chimeric complementation. PMID- 26544114 TI - Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission. AB - BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease free survival, and included five trials involving 1355 participants in the meta analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues. PMID- 26544115 TI - Patient-reported outcomes as assessment tools and predictors of long-term prognosis: a 7-year follow-up study of patients with rheumatoid arthritis. AB - OBJECTIVE: Whether the Boolean-based American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for rheumatoid arthritis (RA) including patient-reported outcome measures (PROMs) for remission are strict for use in daily clinical practice is controversial. This study aimed to clarify the differences in the remission status defined by the criteria, including and excluding PROMs, and to identify the baseline predictors of long-term prognosis using 7-year follow-up data. METHOD: A total of 103 RA outpatients completed the baseline and 7-year follow-up questionnaire surveys. Pain visual analogue scale (VAS) of <= 1/10 was used as a PROM criterion for remission. RESULTS: Only 10 patients achieved full-remission, whereas 18 met the partial-remission criteria excluding PROM at baseline. Although 70.0% of those who achieved full remission at baseline had full or partial remission status, 77.8% of those with partial remission were categorized as having no remission at 7 years. Significant baseline differences in the remission status at 7 years were observed with regard to disease duration, pain VAS, and physical function (Short Form 36 [SF-36]). Stepwise logistic regression analysis adjusted for age and sex identified disease duration and general health perception (SF-36) as independent predictors of full remission. CONCLUSION: Remission criteria including PROMs are stringent but important to achieve sustained remission. Early intensive treatment and efforts to improve patients' health perceptions may result in better prognosis for RA. PMID- 26544116 TI - A Rapid, Selective and Sensitive UPLC-MS/MS Method for Quantification of Nomilin in Rat Plasma and Its Application in a Pharmacokinetic Study. AB - Nomilin is a potential anticancer agent. In this study, a rapid, sensitive, and simple ultra-performance liquid chromatography with tandem mass spectrometry methodology was established and validated to quantify nomilin in rat plasma. Plasma samples were prepared through liquid-liquid extraction using ethyl acetate. Chromatographic separation was performed using an Acquity HSS T3 column. Acetonitrile and water containing 0.1% (v/v) formic acid were used as mobile phases at a flow rate of 0.3 mL/min. Nomilin and quercetin (internal standard) were detected and quantified via a triple quadrupole tandem mass spectrometer in the positive ion mode with multiple reaction monitoring. Tandem mass spectrometry detection was performed by monitoring the fragmentations of m/z 515.3 -> m/z 161.0 and m/z 303.2 -> m/z 153.1 of nomilin and quercetin, respectively. Good linearity (R(2) > 0.996) was observed in the concentration range of 1 ng/mL to 500 ng/mL with a lower limit of quantification of 1 ng/mL for nomilin. The average extraction recoveries of nomilin and quercetin were > 82.3% and 82.0%, respectively. Intra- and interday precisions were less than 15% and accuracy ranged from 85.0% to 90.1%. Indeed, the proposed method was successfully applied to analyze the pharmacokinetics of nomilin after 3 and 50 mg/kg nomilin were administered to rats via intravenous and oral routes, respectively. PMID- 26544117 TI - Antiproliferative Constituents of Geopropolis from the Bee Melipona scutellaris. AB - Fractionation of geopropolis from Melipona scutellaris, guided by antiproliferative activity against two colon cancer cell lines (COLO205 and KM12), led to the isolation of two new cinnamic acid esters, mammea-type coumarins 5,7-dihydroxy-6-(3-methyl-2-butenyl)-8-(4-cinnamoyl-3-methyl-1 oxobutyl)-4-propyl-coumarin (1) and 5,7-dihydroxy-6-(4-cinnamoyl-3-methyl-1 oxobutyl)-4-phenylcoumarin (2), along with five known coumarins, mammeigin (3), hydroxymammeigin (4), mammeisin (5), cinnamoyloxy-mammeisin (6), and mammein (7), and the prenylated benzophenone ent-nemorosone (8). Among the isolated compounds, 5 and 7 showed the highest cell growth inhibition against COLO205 (GI50 9.7 and 10.7 uM, respectively) and KM12 (GI50 12.0 and 10.9 uM, respectively). The presence of these compounds suggests that plants of Clusiaceae family, especially the genera Kielmeyera and Clusia, are likely to be major sources of geopropolis produced by M. scutellaris. PMID- 26544118 TI - Unsaponifiable Fraction of Unripe Fruits of Olea europaea: An Interesting Source of Anti-inflammatory Constituents. AB - The unsaponifiable fraction of olive oil from unripe fruits of Olea europaea at different stages of maturation (from 20 to 32 weeks after flowering) was analyzed by gas chromatography-mass spectrometry in order to select the time associated to the unsaponifiable fraction with the maximal yield in bioactive constituents. According to quantitative gas chromatography-mass spectrometry analysis, the unsaponifiable fraction (2.46% of the total oil) from olive fruits at the 22nd week was found to contain the maximal yield in anti-inflammatory constituents. Its composition was lanosterol (2.60 mg/g oil), stigmasterol (2.15), cycloartanol acetate (2.04), stigmastan-3,5-diene (2.01), obtusifoliol (1.93), cholesta-4,6 dien-3-one (1.42), alpha-amyrin (1.42), alpha-tocopherol (1.32), squalene (1.02), beta-amyrin (0.57), and beta-sitosterol (0.22). At later times, there was a decrease in the quantitative unsaponifiable fraction yield and a qualitative shift in the bioactive constituents. The 22nd week unsaponifiable fraction was subsequently incorporated into a topical preparation to be utilized for a small pilot clinical study in five patients affected by osteoarthrosis. According to clinical observation, the application of the ointment (three times daily for three weeks) attenuated hand and knee joint inflammatory features in all patients and was not associated to any adverse reactions. PMID- 26544119 TI - Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis. AB - Previous studies have demonstrated the presence of the sulfated form of 6 gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6 gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco 2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6 gingerol through sulfation both in vitro and in vivo. PMID- 26544120 TI - Protective Effects of Bacopa Monnieri on Hydrogen Peroxide and Staurosporine: Induced Damage of Human Neuroblastoma SH-SY5Y Cells. AB - Many herbs, and recently their biomass from in vitro cultures, are essential for the treatment of diseases. The aim of this study was to determine the optimal growth of Bacopa monnieri (water hyssop) in an in vitro culture and to examine if extracts of the B. monnieri biomass from the in vitro culture would affect hydrogen peroxide- and staurosporine-induced injury of the human neuroblastoma SH SY5Y cell line. It has been found that B. monnieri at concentrations of 25, 50, and 100 ug/mL inhibited both hydrogen peroxide-induced efflux of lactate dehydrogenase from damaged cells to culture medium and increased cell viability determined by an MTT assay. Moreover, B. monnieri at concentrations of 10, 25, and 50 ug/mL decreased staurosporine-induced activity of an executive apoptotic enzyme-caspase-3 and protected mitochondrial membrane potential. The obtained data indicate that the biomass from the in vitro culture of B. monnieri prevented SH-SY5Y cell damage related to oxidative stress and had the ability to inhibit the apoptotic process. Thus, this study supports the traditional use of B. monnieri as a neuroprotective therapy, and further in vivo studies on the effects of this preparation on morphology and function of nerve cells could lead to its wider application. PMID- 26544121 TI - An unusual business. PMID- 26544122 TI - Drug makers target ubiquitin proteasome pathway anew. PMID- 26544123 TI - FDA raps liquid biopsy firm. PMID- 26544124 TI - Amgen bulks out cardio package. PMID- 26544125 TI - UK funding agencies weigh in on human germline editing. PMID- 26544126 TI - MD Anderson catches immune-oncology wave. PMID- 26544127 TI - AbbVie buys last available priority voucher for $350 million. PMID- 26544128 TI - Hatteras rounds up $90 million to lead biotech rebound in North Carolina. PMID- 26544129 TI - First moss-made drug. PMID- 26544130 TI - Seek 1 million US citizens. PMID- 26544131 TI - Industrial biotechs turn greenhouse gas into feedstock opportunity. PMID- 26544133 TI - Sexed-up beer. PMID- 26544135 TI - Drug pipeline: 3Q15. PMID- 26544136 TI - 3Q15--biotech in the balance. PMID- 26544137 TI - Breathing easier with combinations. PMID- 26544138 TI - Top US universities, institutes for life sciences in 2014. PMID- 26544139 TI - Recasting Asilomar's lessons for human germline editing. PMID- 26544140 TI - Using GlycoDelete to produce proteins lacking plant-specific N-glycan modification in seeds. PMID- 26544141 TI - The ownership question of plant gene and genome intellectual properties. PMID- 26544143 TI - Putting induced pluripotent stem cells to the test. PMID- 26544144 TI - Big thinking for adjuvants. PMID- 26544145 TI - Biological synthesis unbounded? PMID- 26544146 TI - Scaling up phenotyping studies. PMID- 26544148 TI - Third-quarter biotech job picture. PMID- 26544150 TI - S-R compatibility effects on motor potentials associated with hand and foot movements. AB - Two four-choice reaction time (RT) experiments used the lateralized readiness potential (LRP) and the limb selection potential (LSP) to assess the effects of spatial S-R compatibility on motor processes. Individual stimuli were presented at one corner of a square centered at fixation, and each response was made with the left or right hand or foot. In Experiment 1, the correct response was determined by stimulus location, whereas in Experiment 2 it was determined by stimulus identity. Horizontal and vertical compatibility affected both RT and response accuracy, but the LRP and LSP results suggested that compatibility had little or no direct effect on the duration of motor processes. In addition, the results suggest that the relatively new LSP measure is a useful index of motor activation processes. Its insensitivity to horizontal stimulus artifacts makes it especially useful for studying the effects of horizontal spatial compatibility. PMID- 26544151 TI - Factors influencing uptake of familial long QT syndrome genetic testing. AB - Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 +/- 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed. PMID- 26544152 TI - Platelet-to-Lymphocyte Ratio May Predict the Severity of Calcific Aortic Stenosis. AB - BACKGROUND: Platelet-to-lymphocyte ratio (PLR) is an emerging inflammatory indicator which is closely associated with adverse cardiovascular events. Therefore, we aimed to investigate the relationship between PLR and the severity of calcific aortic stenosis (AS). MATERIAL AND METHODS: The study was designed as a retrospective study. A total of 86 consecutive patients with calcific AS were divided into two groups as mild-to-moderate AS and severe AS according to the transaortic mean pressure gradient. PLR levels were calculated from the complete blood count (CBC). RESULTS: Platelet to lymphocyte ratio was significantly higher in severe and mild-to-moderate AS groups when compared to the control subjects (151+/-31.2, p<0.001, 138+/-28.8 vs. 126+/-26.5, p=0.008, respectively). In the subgroup analysis of AS patients, PLR was found to be higher in the severe AS group compared to mild-to-moderate group (p<0.001). A significant correlation was found between PLR and transaortic mean pressure gradient in patients with AS (r=0.421, p<0.001). CONCLUSIONS: Our study results demonstrated that increased PLR correlates with the severity of calcific AS. PMID- 26544154 TI - Arsenic Demethylation by a C.As Lyase in Cyanobacterium Nostoc sp. PCC 7120. AB - Arsenic, a ubiquitous toxic substance, exists mainly as inorganic forms in the environment. It is perceived that organoarsenicals can be demethylated and degraded into inorganic arsenic by microorganisms. Few studies have focused on the mechanism of arsenic demethylation in bacteria. Here, we investigated arsenic demethylation in a typical freshwater cyanobacterium Nostoc sp. PCC 7120. This bacterium was able to demethylate monomethylarsenite [MAs(III)] rapidly to arsenite [As(III)] and also had the ability to demethylate monomethylarsenate [MAs(V)] to As(III). The NsarsI encoding a C.As lyase responsible for MAs(III) demethylation was cloned from Nostoc sp. PCC 7120 and heterologously expressed in an As-hypersensitive strain Escherichia coli AW3110 (DeltaarsRBC). Expression of NsarsI was shown to confer MAs(III) resistance through arsenic demethylation. The purified NsArsI was further identified and functionally characterized in vitro. NsArsI existed mainly as the trimeric state, and the kinetic data were well-fit to the Hill equation with K0.5 = 7.55 +/- 0.33 MUM for MAs(III), Vmax = 0.79 +/- 0.02 MUM min(-1), and h = 2.7. Both of the NsArsI truncated derivatives lacking the C-terminal 10 residues (ArsI10) or 23 residues (ArsI23) had a reduced ability of MAs(III) demethylation. These results provide new insights for understanding the important role of cyanobacteria in arsenic biogeochemical cycling in the environment. PMID- 26544153 TI - Efficient Reassignment of a Frequent Serine Codon in Wild-Type Escherichia coli. AB - Expansion of the genetic code through engineering the translation machinery has greatly increased the chemical repertoire of the proteome. This has been accomplished mainly by read-through of UAG or UGA stop codons by the noncanonical aminoacyl-tRNA of choice. While stop codon read-through involves competition with the translation release factors, sense codon reassignment entails competition with a large pool of endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at a number of different serine and leucine codons in wild-type Escherichia coli. Quantitative LC-MS/MS measurements of amino acid incorporation yields carried out in a selected reaction monitoring experiment revealed that the 3-I-Phe abundance at the Ser208AGU codon in superfolder GFP was 65 +/- 17%. This method also allowed quantification of other amino acids (serine, 33 +/- 17%; phenylalanine, 1 +/- 1%; threonine, 1 +/- 1%) that compete with 3-I-Phe at both the aminoacylation and decoding steps of translation for incorporation at the same codon position. Reassignments of different serine (AGU, AGC, UCG) and leucine (CUG) codons with the matching tRNA(Pyl) anticodon variants were met with varying success, and our findings provide a guideline for the choice of sense codons to be reassigned. Our results indicate that the 3-iodo-l-phenylalanyl-tRNA synthetase (IFRS)/tRNA(Pyl) pair can efficiently outcompete the cellular machinery to reassign select sense codons in wild-type E. coli. PMID- 26544156 TI - Vertically Integrated Multiple Nanowire Field Effect Transistor. AB - A vertically integrated multiple channel-based field-effect transistor (FET) with the highest number of nanowires reported ever is demonstrated on a bulk silicon substrate without use of wet etching. The driving current is increased by 5-fold due to the inherent vertically stacked five-level nanowires, thus showing good feasibility of three-dimensional integration-based high performance transistor. The developed fabrication process, which is simple and reproducible, is used to create multiple stiction-free and uniformly sized nanowires with the aid of the one-route all-dry etching process (ORADEP). Furthermore, the proposed FET is revamped to create nonvolatile memory with the adoption of a charge trapping layer for enhanced practicality. Thus, this research suggests an ultimate design for the end-of-the-roadmap devices to overcome the limits of scaling. PMID- 26544155 TI - Synthesis of (+/-)-Tetrabenazine by Visible Light Photoredox Catalysis. AB - (+/-)-Tetrabenazine was synthesized in six steps from commercially available compounds. The key cyclization substrate was assembled rapidly via Baylis-Hillman and aza-Michael reactions. Annulation of the final ring was achieved through visible light photocatalysis, wherein carbon-carbon bond formation was driven by the oxidation of a tertiary amine. Solvent played a critical role in the photoredox cyclization outcome, whereas methanol led to a mixed ketal, acetonitrile/water (10:1) gave direct cyclization to (+/-)-tetrabenazine and occurred more rapidly. PMID- 26544157 TI - Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity. AB - This rapid report focuses on the pharmacodynamic mechanism of the carboplatin/paclitaxel combination and correlates it with its cytotoxicity. Consistent with the synergistic to additive antitumor activity (the combination index ranging from 0.53 to 0.94), cells exposed to this combination had significantly increased carboplatin-DNA adduct formation when compared to that of carboplatin alone (450 +/- 30 versus 320 +/- 120 adducts per 10(8) nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 10(8) nucleotides per hour in carboplatin alone (p = 0.021). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic. PMID- 26544158 TI - pH-Triggered SrTiO3:Er Nanofibers with Optically Monitored and Controlled Drug Delivery Functionality. AB - The design of multifunctional localized drug delivery systems (LDDSs) has been endeavored in the past decades worldwide. The matrix material of LDDSs is known as a crucial factor for the success of its transformation from the laboratory to clinical practices. Herein, a biocompatible ceramic, strontium titanate (SrTiO3, STO), was utilized as the matrix. A variety of fine Er doped SrTiO3 (STO:Er) nanofibers were fabricated via electrospinning. After the surface functionalization with amino groups, the drug loading capacity of STO:Er nanofibers is dramatically increased. The nanofibers present a rather sustained drug releasing behavior in the media with pH of 7.4, and the release kinetics is significantly accelerated with the decreased pH value from 7.4 to 4.7. Furthermore, the intensity of the spectrum emitted from the STO:Er nanofibers corresponds well with the drug releasing progress under the excitation of near infrared spectrum (~980 nm). Fast drug release behavior (in an acid environment) induces a rapid intensity enhancing effect of photoluminescence emission and vice versa. The main mechanism is attributed to the quenching effect induced by the C Hx groups of IBU molecules with vibration frequencies from 2850 to 3000 cm(-1). Such new STO:Er nanofibers with pH-triggered and optically monitored drug delivery functionalities have therefore been considered as another new localized drug delivery platform for modern tumor diagnosis and therapy. PMID- 26544159 TI - The complete mitochondrial genome of Hemigrammus bleberi. AB - The complete mitochondrial genome of Hemigrammus bleberi was obtained by the traditional polymerase chain reaction (PCR)-based sequencing approach. The mitogenome of H. bleberi was determined as 17 021bp in length, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. Phylogenetic tree was constructed based on the complete mitogenomes of the species and closely related 21 teleost species to assess their phylogenetic relationship and evolution. PMID- 26544160 TI - Updated estimates of typical effective doses for common CT examinations in the UK following the 2011 national review. AB - OBJECTIVE: To investigate the impact of evolving International Commission on Radiological Protection (ICRP) recommendations concerning calculation of effective dose (E) and compare updated typical UK values for common CT examinations with previous data. METHODS: Monte Carlo simulations have provided normalized organ doses relating to 15 CT scanner models and 5 virtual reference adults. Series of representative E/dose-length product (DLP) coefficients were derived for common examinations on the separate bases of not only older stylized mathematical phantoms and voxel phantoms presently recommended by ICRP, but also the 1977, 1990 and 2007 formulations for E. Updated E/DLP coefficients were applied to typical values of DLP from the 2011 UK survey. RESULTS: Changes in ICRP recommendations that have arisen from improving evidence on stochastic risk, influence values of E by up to a factor two for CT examinations of the head and neck, although differences for the trunk typically amount to +/-10%. Adoption of the voxel rather than the mathematical phantoms used previously can lead to further changes in E by a few tens of percent. Updated typical values of E for UK CT examinations range from 2 to 20 mSv. Increases by 20-400% since 2003 arise not only from increases by 30-160% in typical values of DLP, but also increases by 30 90% in relation to E/DLP coefficients for examinations of the trunk. CONCLUSION: Values of E, including updated typical data for UK CT, should be compared with caution in relation to their purpose and underlying factors concerning their calculation. ADVANCES IN KNOWLEDGE: Updated E/DLP coefficients and typical values of E for UK CT, and an appreciation of factors influencing these data. PMID- 26544161 TI - FDG-PET/CT in abdominal post-transplant lymphoproliferative disease. AB - Post-transplant lymphoproliferative disease (PTLD) is a major cause of morbidity and mortality following both solid organ and haematopoietic stem cell transplantation. PTLD has a broad range of manifestations with extranodal involvement more common in the abdomen than nodal involvement. Fludeoxyglucose positron emission tomography/CT (FDG-PET/CT) is sensitive and specific to detect PTLD and can upstage or detect occult PTLD compared with conventional CT imaging. As functional imaging, FDG-PET/CT also has a role in monitoring treatment response. In this pictorial essay, we will discuss the role of FDG-PET/CT in the diagnosis and staging of abdominal PTLD and describe the advantages of functional imaging in assessing response to therapy. PMID- 26544162 TI - Predictors of Parental Mediation Regarding Children's Smartphone Use. AB - Children's addiction to smartphones has become a serious issue, and parental mediation could help prevent children's problematic use of smartphones. This research examined the factors that predict and explain parents' intention to mediate children's behavior over smartphone use. Based on a survey of 460 parents of elementary school students, we found that parental mediation was predicted by (a) parent's own addiction to smartphones, (b) perceived severity of smartphone addiction, and (c) personality traits such as neuroticism, openness, and agreeableness. To the best of our knowledge, this study is the first to examine the predictors of parental mediation regarding children's smartphone addiction, and the findings suggest some strategies to increase parental mediation. PMID- 26544163 TI - Clinical Telemedicine Utilization in Ontario over the Ontario Telemedicine Network. AB - INTRODUCTION: Northern Ontario is a region in Canada with approximately 775,000 people in communities scattered across 803,000 km(2). The Ontario Telemedicine Network (OTN) facilitates access to medical care in areas that are often underserved. We assessed how OTN utilization differed throughout the province. MATERIALS AND METHODS: We used OTN medical service utilization data collected through the Ontario Health Insurance Plan and provided by the Ministry of Health and Long Term Care. Using census subdivisions grouped by Northern and Southern Ontario as well as urban and rural areas, we calculated utilization rates per fiscal year and total from 2008/2009 to 2013/2014. We also used billing codes to calculate utilization by therapeutic area of care. RESULTS: There were 652,337 OTN patient visits in Ontario from 2008/2009 to 2013/2014. Median annual utilization rates per 1,000 people were higher in northern areas (rural, 52.0; urban, 32.1) than in southern areas (rural, 6.1; urban, 3.1). The majority of usage in Ontario was in mental health and addictions (61.8%). Utilization in other areas of care such as surgery, oncology, and internal medicine was highest in the rural north, whereas primary care use was highest in the urban south. CONCLUSIONS: Utilization was higher and therapeutic areas of care were more diverse in rural Northern Ontario than in other parts of the province. Utilization was also higher in urban Northern Ontario than in Southern Ontario. This suggests that telemedicine is being used to improve access to medical care services, especially in sparsely populated regions of the province. PMID- 26544164 TI - Study on the homology of the genomes of tetraploid Asiatic lilies (Lilium) using FISH. AB - Asiatic lily cultivars, bred by hybridization and (or) chromosome doubling of species of section Sinomartagon of Lilium, are diploid, triploid, or tetraploid, but the homology of the genomes among species of section Sinomartagon and Asiatic lilies remains unclear. In the present research, two tetraploid Asiatic cultivars were analyzed, using 45S rDNA as probe, for their FISH karyotypes and their chromosomal association, anaphase I, telophase II, and pollen viability were surveyed to assess the multivalent segregation. Chromosomal assortment of six progenies of the two tetraploid cultivars were also investigated. The results showed that the tetraploid cultivars had similar FISH karyotypes, they predominantly formed multivalents, and these were equally separated because their anaphase I, telophase II, and pollen viability were similar to those of diploid species. Apart from minor variations, FISH karyotypes of progenies were similar to each other and to their parents. Based on these results and considering the high crossability among species of section Sinomartagon and (or) Asiatic lilies, we concluded that species of section Sinomartagon and their resulting cultivars share a common genome; thus, polyploidy Asiatic lilies are autopolyploid. PMID- 26544165 TI - [Interaction between Amoxicillin Clavulanic Acid and Fluindione: Two Case Reports]. AB - Several drug classes, such as antibiotics, may interact with antivitamin K and increase anticoagulant effect. To date, interaction between fluindione and amoxicillin/clavulanic acid is neither described in the literature, nor specified in the summary of product characteristics. We report the cases of two patients who overdose fluindione after administration of amoxicillin/clavulanic acid. PMID- 26544167 TI - Ultrathin PtPdCu Nanowires Fused Porous Architecture with 3D Molecular Accessibility: An Active and Durable Platform for Methanol Oxidation. AB - It is desirable but challenging to develop active and durable low-Pt catalysts for next-generation fuel cells. Herein, a three-dimensional porous PtPdCu architecture with ultrathin nanowires was obtained through a simple, rapid and aqueous method. This PtPdCu catalyst showed the remarkable performance for methanol oxidation reaction with a 6.5 times enhancement in precious-metal-based mass activity, a 7.2 times enhancement in specific activity and a better durability in comparison with a standard Pt/C catalyst. According to the structure-activity analysis, these enhancements were due to the beneficial structural feature and the multicomponent synergy effect. PMID- 26544166 TI - Update on the treatment of hypothyroidism. AB - PURPOSE OF REVIEW: Differentiated thyroid cancer is a malignancy that is rapidly increasing in frequency. As thyroidectomy plays a central role in the treatment of thyroid cancer, it is incumbent on physicians treating this patient group to be well versed in the intricacies of treating hypothyroidism. RECENT FINDINGS: Treatment of hypothyroidism may be refined by careful attention to dose selection, monitoring of therapy and achievement of thyrotropin goals that are specific to the individual patient's overall clinical situation. These goals are common not only to patients with a sole diagnosis of hypothyroidism, as discussed in the recent American Thyroid Association Guidelines, but also to patients with hypothyroidism in the setting of thyroid cancer. Several recent studies have illuminated our understanding of the benefits and risks of thyrotropin suppression therapy in patients with differentiated thyroid cancer. Multiple studies of combination therapy with levothyroxine and liothyronine for treating hypothyroidism have not led to a clear conclusion about its benefits over levothyroxine monotherapy. Animal studies have advanced our understanding of the altered serum and tissue milieu that characterizes levothyroxine monotherapy. Crossing the bridge from this translational research into clinical research using sustained release triiodothyronine preparations may ultimately enhance the health of our patients. SUMMARY: Continued refinement of our understanding of thyroid status and our ability to flawlessly implement thyroid hormone replacement is an active area of research. PMID- 26544168 TI - Microscopic Posterior Transdural Resection of Cervical Retro-Odontoid Pseudotumors. AB - Retro-odontoid pseudotumors are noninflammatory masses formed posterior to the odontoid process. Because of their anatomy, the optimal surgical approach for resecting pseudotumors is controversial. Conventionally, 3 approaches are used: the anterior transoral approach, the lateral approach, and the posterior extradural approach; however, each approach has its limitations. The posterior extradural approach is the most common; however, it remains challenging due to severe epidural veins. Although regression of pseudotumors after fusion surgery has been reported, direct decompression and a pathologic diagnosis are ideal when the pseudotumor is large. We therefore developed a new microscopic surgical technique; transdural resection. After C1 laminectomy, the dorsal and ventral dura was incised while preserving the arachnoid. Removal of the pseudotumor was performed and both of the dura were repaired. The patient's clinical symptoms subsequently improved and the pathologic findings showed degenerative fibrocartilaginous tissue. In addition, no neurological deterioration, central spinal fluid leakage, or arachnoiditis was observed. Currently, the usefulness of the transdural approach has been reported for cervical and thoracic disk herniation. According to our results, the transdural approach is recommended for resection of retro-odontoid pseudotumors because it enables direct decompression of the spinal cord and a pathologic diagnosis. PMID- 26544169 TI - In Situ Observation of Active Oxygen Species in Fe-Containing Ni-Based Oxygen Evolution Catalysts: The Effect of pH on Electrochemical Activity. AB - Ni-based oxygen evolution catalysts (OECs) are cost-effective and very active materials that can be potentially used for efficient solar-to-fuel conversion process toward sustainable energy generation. We present a systematic spectroelectrochemical characterization of two Fe-containing Ni-based OECs, namely nickel borate (Ni(Fe)-B(i)) and nickel oxyhydroxide (Ni(Fe)OOH). Our Raman and X-ray absorption spectroscopy results show that both OECs are chemically similar, and that the borate anions do not play an apparent role in the catalytic process at pH 13. Furthermore, we show spectroscopic evidence for the generation of negatively charged sites in both OECs (NiOO(-)), which can be described as adsorbed "active oxygen". Our data conclusively links the OER activity of the Ni based OECs with the generation of those sites on the surface of the OECs. The OER activity of both OECs is strongly pH dependent, which can be attributed to a deprotonation process of the Ni-based OECs, leading to the formation of the negatively charged surface sites that act as OER precursors. This work emphasizes the relevance of the electrolyte effect to obtain catalytically active phases in Ni-based OECs, in addition to the key role of the Fe impurities. This effect should be carefully considered in the development of Ni-based compounds meant to catalyze the OER at moderate pHs. Complementarily, UV-vis spectroscopy measurements show strong darkening of those catalysts in the catalytically active state. This coloration effect is directly related to the oxidation of nickel and can be an important factor limiting the efficiency of solar-driven devices utilizing Ni-based OECs. PMID- 26544171 TI - Systematic Review and Meta-analyses Investigating Whether Risk Stratification Explains Lower Rates of Coronary Angiography Among Women With Non-ST-Segment Elevation Acute Coronary Syndrome. AB - BACKGROUND: Guidelines recommend that all non-ST-segment elevation acute coronary syndrome (NSTEACS) patients with high-risk features receive a coronary angiogram. We hypothesised that the widely reported gender disparity in the use of angiography might be the result of women more frequently being stratified into the lower-risk category. OBJECTIVES: The aim of the study was to review studies reporting risk stratification of NSTEACS patients by gender, compare risk profiles, and assess impact on use of coronary angiography. METHODS: PubMed, Scopus, and EMBASE databases were searched on June 17, 2014, using MeSH terms/subheadings and/or key words with no further limits. The search revealed 1230 articles, of which 25 met our objective. RESULTS: Among the 28 risk stratified populations described in the 25 articles, women were more likely to be stratified as high-risk in 13 studies; men were more likely to be stratified as high-risk in 3 studies. After meta-analyses, women had a 23% higher odds of being stratified as high-risk than did men (P = .001). Lower-risk patients were more likely to receive an angiogram in 15 study populations. CONCLUSIONS: Contrary to our hypothesis, this review showed that women with NSTEACS are more likely than men to be considered high-risk when stratified using a range of risk assessment methods. Lower rates of angiography in women form part of a broader treatment risk paradox, which may involve gender bias in the selection of patients for invasive therapy. PMID- 26544172 TI - Socioeconomic and Behavioral Characteristics Associated With Metabolic Syndrome Among Overweight/Obese School-age Children. AB - BACKGROUND: Obesity in children comprises a significant public health concern in Korea. As with increased prevalence of overweight and obesity among children, risk factors for metabolic syndrome (MetS) have also increased in this population. OBJECTIVE: The purpose was to examine behavioral and socioeconomic factors that were associated with biomarkers of MetS among overweight/obese school-age children. METHODS: A cross-sectional study was conducted, and a convenience sample of 75 overweight/obese school-age children participated. Socioeconomic and behavioral characteristics, anthropometric measurements, and physiologic examinations were studied. The data were analyzed using an analysis of covariance and logistic regression. RESULTS: Metabolic syndrome was diagnosed in 27.8% of our population. Severe stress was significantly associated with elevated systolic blood pressure (P < .05). Among the family characteristics, children's perception of family income (wealthy and very wealthy) and mother's education level (high school or less) were associated with diagnoses of MetS in children (P < .05). CONCLUSIONS: The results indicated that certain socioeconomic and behavioral characteristics were associated with risk factors of MetS, and therefore, interventions to modify these risk factors are needed to promote the healthy development of overweight/obese school-age children. PMID- 26544170 TI - Interventions Promoting Physical Activity in African American Women: An Integrative Review. AB - BACKGROUND: Physical inactivity significantly impacts mortality worldwide. Physical inactivity is a modifiable risk factor for obesity, diabetes, cardiovascular disease, and other chronic conditions. African American women in the United States have the highest rates of physical inactivity when compared with other gender/ethnic groups. A paucity of research promoting physical activity (PA) in African American women has been previously identified. The purpose of this review was to identify intervention strategies and outcomes in studies designed to promote PA in African American women. METHODS: Interventions that promoted PA in African American women published between 2000 and May 2015 were included. A comprehensive search of the literature was performed in Health Source: Nursing/Academic Edition, PsycINFO, CINAHL Complete, and MEDLINE Complete databases. Data were abstracted and synthesized to examine interventions, study designs, theoretical frameworks, and measures of PA. RESULTS: Mixed findings (both significant and nonsignificant) were identified. Interventions included faith-based, group-based, and individually focused programs. All studies (n = 32) included measures of PA; among the studies, self-report was the predominant method for obtaining information. Half of the 32 studies focused on PA, and the remaining studies focused on PA and nutrition. Most studies reported an increase in PA or adherence to PA. This review reveals promising strategies for promoting PA. CONCLUSIONS: Future studies should include long-term follow-up, larger sample sizes, and objective measures of PA. Additional research promoting PA in African American women is warranted, particularly in studies that focus on increasing PA in older African American women. PMID- 26544173 TI - Effects of a Structured Discharge Planning Program on Perceived Functional Status, Cardiac Self-efficacy, Patient Satisfaction, and Unexpected Hospital Revisits Among Filipino Cardiac Patients: A Randomized Controlled Study. AB - BACKGROUND: Cardiovascular diseases remain the leading cause of morbidity and mortality among Filipinos and are responsible for a very large number of hospital readmissions. Comprehensive discharge planning programs have demonstrated positive benefits among various populations of patients with cardiovascular disease, but the clinical and psychosocial effects of such intervention among Filipino patients with acute myocardial infarction (AMI) have not been studied. AIMS/OBJECTIVES: In this study we aimed to determine the effectiveness of a nurse led structured discharge planning program on perceived functional status, cardiac self-efficacy, patient satisfaction, and unexpected hospital revisits among Filipino patients with AMI. METHODS: A true experimental (randomized control) 2 group design with repeated measures and data collected before and after intervention and at 1-month follow-up was used in this study. Participants were assigned to either the control (n = 68) or the intervention group (n = 75). Intervention participants underwent a 3-day structured discharge planning program implemented by a cardiovascular nurse practitioner, which is comprised of a series of individualized lecture-discussion, provision of feedback, integrative problem solving, goal setting, and action planning. Control participants received standard routine care. Measures of functional status, cardiac self-efficacy, and patient satisfaction were measured at baseline; cardiac self-efficacy and patient satisfaction scores were measured prior to discharge, and perceived functional status and number of revisits were measured 1 month after discharge. RESULTS: Participants in the intervention group had significant improvement in functional status, cardiac self-efficacy, and patient satisfaction scores at baseline and at follow-up compared with the control participants. Furthermore, participants in the intervention group had significantly fewer hospital revisits compared with those who received only standard care. CONCLUSION: The results demonstrate that a nurse-led structured discharge planning program is an effective intervention in improving perceived functional health status, cardiac self-efficacy, and patient satisfaction, while reducing the number of unexpected hospital revisits, among Filipino patients with AMI. It is recommended that this intervention be incorporated in the optimal care of patients being discharged with an AMI. PMID- 26544174 TI - Micronutrient Deficiency Independently Predicts Adverse Health Outcomes in Patients With Heart Failure. AB - BACKGROUND: Despite growing evidence on the important role of micronutrients in prognosis of heart failure (HF), there has been limited research that micronutrient deficiency predicts health outcomes in patients with HF. PURPOSE: The aim of this study was to determine whether micronutrient deficiency independently predicts adverse health outcomes. METHODS: A total of 113 consecutive outpatients with HF completed a 3-day food diary to measure intake of 15 micronutrients. The Computer Aided Nutrition Analysis Program for Professionals was used to analyze the food diaries and determine dietary micronutrient deficiencies. Patients completed the Minnesota Living With HF Questionnaire to assess health-related quality of life (HRQoL) and were followed up for 1 year to determine cardiac-related hospitalization or cardiac death. Hierarchical multiple linear regressions and Cox proportional hazard regressions were used to determine whether micronutrient deficiencies predicted health outcomes. RESULTS: Fifty-eight patients (51%) had at least 3 micronutrient deficiencies (range, 0-14). Calcium, magnesium, and vitamin D were the most common micronutrient deficiencies. Micronutrient deficiency was independently associated with worse HRQoL (beta = .187, P = .025) in hierarchical multiple linear regression. Thirty-nine patients were hospitalized or died during 1-year follow-up because of cardiac problems. The number of micronutrient deficiencies independently predicted cardiac event-free survival (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28). CONCLUSIONS: These findings show that micronutrient deficiency independently predicted poor HRQoL and earlier cardiac event-free survival in patients with HF. Further research is needed to provide for specific dietary guidelines for better health outcomes in HF patients. PMID- 26544175 TI - A Systematic Review of mHealth-Based Heart Failure Interventions. AB - BACKGROUND: The popularity of mobile phones and similar mobile devices makes it an ideal medium for delivering interventions. This is especially true with heart failure (HF) interventions, in which mHealth-based HF interventions are rapidly replacing their telephone-based predecessors. PURPOSE: This systematic review examined the impact of mHealth-based HF management interventions on HF outcomes. The specific aims of the systematic review are to (1) describe current mHealth based HF interventions and (2) discuss the impact of these interventions on HF outcomes. METHODS: PubMed, CINAHL Plus, EMBASE, PsycINFO, and Scopus were systematically searched for randomized controlled trials or quasi-experimental studies that tested mHealth interventions in people with HF using the terms Heart Failure, Mobile Health, mHealth, Telemedicine, Text Messaging, Texting, Short Message Service, Mobile Applications, and Mobile Apps. CONCLUSIONS: Ten articles, representing 9 studies, were included in this review. The majority of the studies utilized mobile health technology as part of an HF monitoring system, which typically included a blood pressure-measuring device, weighing scale, and an electrocardiogram recorder. The impact of the mHealth interventions on all-cause mortality, cardiovascular mortality, HF-related hospitalizations, length of stay, New York Heart Association functional class, left ventricular ejection fraction, quality of life, and self-care were inconsistent at best. IMPLICATIONS: Further research is needed to conclusively determine the impact of mHealth interventions on HF outcomes. The limitations of the current studies (eg, inadequate sample size, quasi-experimental design, use of older mobile phone models, etc) should be taken into account when designing future studies. PMID- 26544176 TI - Exposure of Cleft Lip and Palate Patients to Toxic Elements Released during Orthodontic Treatment in the Study of Non-Invasive Matrices. AB - THE OBJECTIVE: The aim of the study was evaluation of metal ions (nickel and chromium) released from orthodontic appliances in cleft lip and palate patients and the usefulness of non-invasive matrices (saliva and hair). MATERIALS AND METHODS: The material studied consisted of 100 individuals, including 59 females and 41 males of 5 to 16 years of age, which were divided into 3 groups: experimental-patients with cleft lip and palate (36 individuals, the average treatment time 5.74 years); control group-patients without cleft lip and palate, during orthodontic treatment (32 individuals, the average treatment time 1.78 years) and the control group patients without cleft lip and palate, without any orthodontic appliances (32 individuals). Samples (saliva, hair) were collected and subjects underwent a survey by questionnaire. Multi-elemental analyses of the composition of non-invasive matrices was conducted in an accredited laboratory by inductively coupled plasma spectrometry technique ICP-OES. The results were reported as mean contents of particular elements (Cd, Cr, Cu, Fe, Mn, Mo, Ni, Si) in hair and in saliva. RESULTS: The concentration of Cr, Ni, Fe and Cu ions in saliva of cleft lip and palate patients were several times higher as compared with not treated orthodontically control groups and higher than in the group with orthodontic appliances. Among the assessed matrices, hair of cleft lip and palate patients seem to be not a meaningful biomarker. CONCLUSION: It was found that orthodontic appliances used in long-term treatment of cleft lip and palate patients do not release toxic levels of Cr and Ni ions. PMID- 26544177 TI - Determinants of Visceral Leishmaniasis: A Case-Control Study in Gedaref State, Sudan. AB - BACKGROUND: Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital's catchment area, Gedaref State, Sudan. METHODS: From September 2012 to July 2013, in an unmatched case control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. RESULTS: Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard's immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. DISCUSSION AND CONCLUSION: Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures. PMID- 26544178 TI - Mechanism of Focal Adhesion Kinase Mechanosensing. AB - Mechanosensing at focal adhesions regulates vital cellular processes. Here, we present results from molecular dynamics (MD) and mechano-biochemical network simulations that suggest a direct role of Focal Adhesion Kinase (FAK) as a mechano-sensor. Tensile forces, propagating from the membrane through the PIP2 binding site of the FERM domain and from the cytoskeleton-anchored FAT domain, activate FAK by unlocking its central phosphorylation site (Tyr576/577) from the autoinhibitory FERM domain. Varying loading rates, pulling directions, and membrane PIP2 concentrations corroborate the specific opening of the FERM-kinase domain interface, due to its remarkably lower mechanical stability compared to the individual alpha-helical domains and the PIP2-FERM link. Analyzing downstream signaling networks provides further evidence for an intrinsic mechano-signaling role of FAK in broadcasting force signals through Ras to the nucleus. This distinguishes FAK from hitherto identified focal adhesion mechano-responsive molecules, allowing a new interpretation of cell stretching experiments. PMID- 26544179 TI - Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High Permissive and Low-Permissive Cell Lines. AB - Chronic hepatitis C virus (HCV) infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT PCR. The differential expression of Glutathione S-transferase P (GSTP1), Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), carboxylesterase 1 (CES1), vimentin, Proteasome activator complex subunit1 (PSME1), and Cathepsin B (CTSB) were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication. PMID- 26544180 TI - Seasonal Variations of Complete Blood Count and Inflammatory Biomarkers in the US Population - Analysis of NHANES Data. AB - BACKGROUND: Recent studies reported seasonal differences in gene expression in white blood cells, adipose tissue, and inflammatory biomarkers of the immune system. There is no data on the seasonal variations of these biomarkers in the US general population of both children and adults. Then aim of this study is to explore the seasonal trends in complete blood count (CBC), and C-reactive protein (CRP) in a large non-institutionalized US population. METHODS: Seven cross sectional data collected in the National Health and Nutrition Examination Survey (NHANES) during 1999-2012 were aggregated; participants reporting recent use of prescribed steroids, chemotherapy, immunomodulators and antibiotics were excluded. Linear regression models were used to compare levels of CBC and CRP between winter-spring (November-April) and summer-fall (May-October), adjusting for demographics, personal behavioral factors, and chronic disease conditions. RESULTS: A total of 27,478 children and 36,644 adults (>=18 years) were included in the study. Levels of neutrophils, white blood cell count (WBC), and CRP were higher in winter-spring than summer-fall (p<=0.05). Red blood cell components were lower in winter-spring than in summer-fall, while the opposite was seen for platelets. CONCLUSIONS: This large population-based study found notable seasonal variations in blood cell composition and inflammatory biomarkers, with a more pro inflammatory immune system seen in winter-spring than summer-fall. The red blood cell patterns could have implications for the observed cardio-vascular seasonality. PMID- 26544182 TI - Canopy Interception for a Tallgrass Prairie under Juniper Encroachment. AB - Rainfall partitioning and redistribution by canopies are important ecohydrological processes underlying ecosystem dynamics. We quantified and contrasted spatial and temporal variations of rainfall redistribution for a juniper (Juniperus virginiana, redcedar) woodland and a tallgrass prairie in the south-central Great Plains, USA. Our results showed that redcedar trees had high canopy storage capacity (S) ranging from 2.14 mm for open stands to 3.44 mm for closed stands. The canopy funneling ratios (F) of redcedar trees varied substantially among stand type and tree size. The open stands and smaller trees usually had higher F values and were more efficient in partitioning rainfall into stemflow. Larger trees were more effective in partitioning rainfall into throughfall and no significant changes in the total interception ratios among canopy types and tree size were found. The S values were highly variable for tallgrass prairie, ranging from 0.27 mm at early growing season to 3.86 mm at senescence. As a result, the rainfall interception by tallgrass prairie was characterized by high temporal instability. On an annual basis, our results showed no significant difference in total rainfall loss to canopy interception between redcedar trees and tallgrass prairie. Increasing structural complexity associated with redcedar encroachment into tallgrass prairie changes the rainfall redistribution and partitioning pattern at both the temporal and spatial scales, but does not change the overall canopy interception ratios compared with unburned and ungrazed tallgrass prairie. Our findings support the idea of convergence in interception ratio for different canopy structures under the same precipitation regime. The temporal change in rainfall interception loss from redcedar encroachment is important to understand how juniper encroachment will interact with changing rainfall regime and potentially alter regional streamflow under climate change. PMID- 26544181 TI - Quantitative 'Omics Analyses of Medium Chain Length Polyhydroxyalkanaote Metabolism in Pseudomonas putida LS46 Cultured with Waste Glycerol and Waste Fatty Acids. AB - Transcriptomes and proteomes of Pseudomonas putida LS46 cultured with biodiesel derived waste glycerol or waste free fatty acids, as sole carbon sources, were compared under conditions that were either permissive or non-permissive for synthesis of medium chain length polyhydroxyalkanoates (mcl-PHA). The objectives of this study were to elucidate mechanisms that influence activation of biopolymer synthesis, intra-cellular accumulation, and monomer composition, and determine if these were physiologically specific to the carbon sources used for growth of P. putida LS46. Active mcl-PHA synthesis by P. putida LS46 was associated with high expression levels of key mcl-PHA biosynthesis genes and/or gene products including monomer-supplying proteins, PHA synthases, and granule associated proteins. 'Omics data suggested that expression of these genes were regulated by different genetic mechanisms in P. putida LS46 cells in different physiological states, when cultured on the two waste carbon sources. Optimal polymer production by P. putida LS46 was primarily limited by less efficient glycerol metabolism during mcl-PHA synthesis on waste glycerol. Mapping the 'Omics data to the mcl-PHA biosynthetic pathway revealed significant variations in gene expression, primarily involved in: 1) glycerol transportation; 2) enzymatic reactions that recycle reducing equivalents and produce key mcl-PHA biosynthesis pathway intermediates (e.g. NADH/NADPH, acetyl-CoA). Active synthesis of mcl-PHAs was observed during exponential phase in cultures with waste free fatty acids, and was associated with the fatty acid beta-oxidation pathway. A putative Thioesterase in the beta-oxidation pathway that may regulate the level of fatty acid beta-oxidation intermediates, and thus carbon flux to mcl PHA biosynthesis, was highly up-regulated. Finally, the data suggested that differences in expression of selected fatty acid metabolism and mcl-PHA monomer supplying enzymes may play a role in determining the monomer composition of mcl PHA polymers. Understanding the relationships between genome content, gene and gene product expression, and how these factors influence polymer synthesis, will aid in optimization of mcl-PHA production by P. putida LS46 using biodiesel waste streams. PMID- 26544183 TI - Optimizing Mycobacterial Culture in Smear-Negative, Human Immunodeficiency Virus Infected Tuberculosis Cases. AB - INTRODUCTION: Tuberculosis (TB) is a significant public health problem and the diagnosis in human immunodeficiency virus (HIV)-infected individuals is challenging. The use of mycobacterial culture remains an important complementary tool and optimizing it has important benefits. We sought to determine the effect of an increase in the number of specimens evaluated, addition of nutritional supplementation to the culture medium, sputum appearance and volume on diagnostic yield and time to detection of pulmonary TB among smear-negative, HIV-infected adults. METHODS: In this prospective study conducted at the Tshwane District Hospital and Academic TB Laboratory, Pretoria, South Africa we collected three sputum specimens an hour apart from presumptive TB cases at an antiretroviral treatment site. We analysed specimens from 236 patients. Specimen appearance and volume were recorded. All specimens were processed for culture using both standard and supplemented media. RESULTS: A single specimen identified 79% of PTB cases using standard media; the second and third specimens added 12.5% and 8.3% respectively. Media supplementation, sputum appearance and specimen volume had no effect on culture yield or contamination rates. The mean time to detection was reduced from 19.8 days in standard cultures to 11.8 days in nutrient supplemented cultures (p = 0.002). For every 1 ml increase in sputum volume, time to detection was decreased by a factor of 0.797 (p = 0.011). CONCLUSION: Use of an inexpensive culture supplement substantially reduced time to detection and could contribute to reducing treatment delay among HIV-infected cases. PMID- 26544185 TI - Movements, Home Range and Site Fidelity of Snapper (Chrysophrys auratus) within a Temperate Marine Protected Area. AB - Understanding the movement dynamics of marine fish provides valuable information that can assist with species management, particularly regarding protection within marine protected areas (MPAs). We performed an acoustic tagging study implemented within the Port Stephens-Great Lakes Marine Park on the mid-north coast of New South Wales, Australia, to assess the movement patterns, home range and diel activity of snapper (Chrysophrys auratus; Sparidae); a species of significant recreational and commercial fishing importance in Australia. The study focused on C. auratus movements around Cabbage Tree Island, which is predominantly a no-take sanctuary zone (no fishing), with an array of acoustic stations deployed around the island and adjacent reefs and islands. Thirty C. auratus were tagged with internal acoustic tags in November 2010 with their movements recorded until September 2014. Both adult and juvenile C. auratus were observed to display strong site fidelity to Cabbage Tree Island with a mean 12-month residency index of 0.83 (range = 0 low to 1 high). Only three fish were detected on acoustic receivers away from Cabbage Tree Island, with one fish moving a considerable distance of ~ 290 kms over a short time frame (46 days). The longest period of residency recorded at the island was for three fish occurring regularly at the site for a period of 1249 days. Chrysophrys auratus displayed strong diurnal behaviour and detection frequency was significantly higher during the day than at night; however, there was no significant difference in detection frequency between different hours. This study demonstrates that even small-scale protected areas can benefit C. auratus during multiple life-history stages as it maintains a small home range and displays strong site fidelity over a period of 3 years. PMID- 26544184 TI - Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells. AB - Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-kappaB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-kappaB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-kappaB-related signaling pathways and to the activation of anti-apoptotic proteins. PMID- 26544186 TI - Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events. AB - BACKGROUND: The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) estimates the burden of cardiovascular risk in renal transplant recipients (RTR). Our recent study of 95 RTR reported the 7-year median risk of cardiovascular events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the inflammatory response may play a role in the pathogenesis of cardiovascular disease (CVD), we extended this study to identify which ILs are associated with high cardiovascular risk in this population. METHODS: Twenty-two ILs were measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 normal controls. Stepwise analysis after multivariate determination of significant demographic and inflammatory variables was performed between the high and low-CVD risk groups (which were arbitrarily set at scores <10% and >=20%, respectively). Normalized data was presented as mean +/- SD and non-normalized data as median (minimum-maximum). Significance was measured at <0.05. RESULTS: 27.5% of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95 percentile of the normal control levels. In the non-parametric analysis IL 6, 9, 16, 17 and 33 were significantly higher in the high-risk group compared to the control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the only IL that remained significantly higher than the control and low-risk groups (p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile of control value in the low and high-risk groups were 15.6% and 52.0%, respectively (p<0.002). UVA of factors significant to high IL-33 levels included estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum phosphorus, microalbuminuria and age also remained significant in the multivariate analysis. CONCLUSION: Circulating IL-33 level is positively associated with high CRCRTR-MACE score. Diminished eGFR, age, diabetes, serum phosphorus and microalbuminurea demonstrate significant relationship with elevated IL-33 levels, supporting the possible pathognomonic role of IL-33 in the cardiovascular burden in RTR. PMID- 26544187 TI - p31comet-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2. AB - Mad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer. p31comet is a Mad2 interacting protein that serves as a spindle checkpoint silencer at mitosis. In this study, we showed that p31comet-induced apoptosis and senescence occur via counteraction of Mad2 activity. Upon retroviral transduction of p31comet, the majority of human cancer cell lines tested lost the ability to form colonies in a low-density seeding assay. Cancer cells with p31comet overexpression underwent distinct apoptosis and/or senescence, irrespective of p53 status, confirming the cytotoxicity of p31comet. Interestingly, both cytotoxic and Mad2 binding activities were eliminated upon deletion of the C-terminal 30 amino acids of p31comet. Point mutation or deletion of the region affecting Mad2 binding additionally abolished cytotoxic activity. Consistently, wild-type Mad2 interacting with p31comet, but not its non-binding mutant, inhibited cell death, indicating that the mechanism of p31comet-induced cell death involves Mad2 inactivation. Our results clearly suggest that the regions of p31comet affecting interactions with Mad2, including the C-terminus, are essential for induction of cell death. The finding that p31comet-induced cell death is mediated by interactions with Mad2 that lead to its inactivation is potentially applicable in anticancer therapy. PMID- 26544188 TI - Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice. AB - Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2-24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished gammaH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR treated females. While DXR significantly increased the "infertility index" (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse model, suggesting this clinically available drug may provide ovarian protection for cancer patients. PMID- 26544189 TI - Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting. AB - Familial recurrent hydatidiform mole (RHM) is a maternal-effect autosomal recessive disorder usually associated with mutations of the NLRP7 gene. It is characterized by HM with excessive trophoblastic proliferation, which mimics the appearance of androgenetic molar conceptuses despite their diploid biparental constitution. It has been proposed that the phenotypes of both types of mole are associated with aberrant genomic imprinting. However no systematic analyses for imprinting defects have been reported. Here, we present the genome-wide methylation profiles of both spontaneous androgenetic and biparental NLRP7 defective molar tissues. We observe total paternalization of all ubiquitous and placenta-specific differentially methylated regions (DMRs) in four androgenetic moles; namely gain of methylation at paternally methylated loci and absence of methylation at maternally methylated regions. The methylation defects observed in five RHM biopsies from NLRP7 defective patients are restricted to lack-of methylation at maternal DMRs. Surprisingly RHMs from two sisters with the same missense mutations, as well as consecutive RHMs from one affected female show subtle allelic methylation differences, suggesting inter-RHM variation. These epigenotypes are consistent with NLRP7 being a maternal-effect gene and involved in imprint acquisition in the oocyte. In addition, bioinformatic screening of the resulting methylation datasets identified over sixty loci with methylation profiles consistent with imprinting in the placenta, of which we confirm 22 as novel maternally methylated loci. These observations strongly suggest that the molar phenotypes are due to defective placenta-specific imprinting and over expression of paternally expressed transcripts, highlighting that maternal-effect mutations of NLRP7 are associated with the most severe form of multi-locus imprinting defects in humans. PMID- 26544190 TI - Phenotypic Buffering in a Monogenean: Canalization and Developmental Stability in Shape and Size of the Haptoral Anchors of Ligophorus cephali (Monogenea: Dactylogyridae). AB - Phenotypic variation results from the balance between sources of variation and counteracting regulatory mechanisms. Canalization and developmental stability are two such mechanisms, acting at two different levels of regulation. The issue of whether or not they act concurrently as a common developmental buffering capacity has been subject to debate. We used geometric morphometrics to quantify the mechanisms that guarantee phenotypic constancy in the haptoral anchors of Ligophorus cephali. Canalization and developmental stability were appraised by estimating inter- and intra-individual variation, respectively, in size and shape of dorsal and ventral anchors. The latter variation was estimated as fluctuating asymmetry (FA) between anchor pairs. The general-buffering-capacity hypothesis was tested by two different methods based on correlations and Principal Components Analyses of the different components of size and shape variation. Evidence for FA in the dorsal and ventral anchors in both shape and size was found. Our analyses supported the hypothesis of a general developmental buffering capacity. The evidence was more compelling for shape than for size and, particularly, for the ventral anchors than for the dorsal ones. These results are in line with previous studies of dactylogyrids suggesting that ventral anchors secure a firmer, more permanent attachment, whereas dorsal anchors are more mobile. Because fixation to the host is crucial for survival in ectoparasites, we suggest that homeostatic development of the ventral anchors has been promoted to ensure the morphological constancy required for efficient attachment. Geometric morphometrics can be readily applied to other host-monogenean models, affording not only to disentangle the effects of canalization and developmental stability, as shown herein, but to further partition the environmental and genetic components of the former. PMID- 26544191 TI - Variability of the Left Atrial Appendage in Human Hearts. AB - Atrial fibrillation increases the risk of thrombus formation. It is commonly responsible for cerebral stroke whereas less frequently for pulmonary embolism. The aim of the study was to describe the morphology of the left atrial appendage in the human heart with respect to sex, age and weight. Macroscopic examination was carried out on 100 left appendages taken from the hearts of the patients aged 18-77, both sexes. All hearts preserved in 4% water solution of formaldehyde carried neither marks of coronary artery disease nor congenital abnormalities. Three axes of appendage orientation were performed. After the appendage had been cut off, morphological examination was performed in long and perpendicular axes. Measurements of the appendages were taken from anatomical specimens and their silicone casts. We classified the left atrial appendage into 4 morphological groups according to the number of lobes. Most left atrial appendages in female population were composed of 2 lobes. In the male group typically 2 or 3-lobed appendages were observed. The mean left atrial appendage orifice ranged from 12.0 to 16.0 mm and the most significant difference in the orifices between males and females was observed in LAA type 2 (about 3.3 mm). A smaller orifice and narrower, tubular shape of the LAA lobes could explain a higher risk of thrombus formation during nonvalvular atrial fibrillation in women. Knowledge of anatomical variability of the LAA helps diagnose some undefined echoes in the appendage during transesophageal echocardiographic examination. PMID- 26544192 TI - Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes. AB - BACKGROUND: We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM). METHODS: In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am), as well as glycemic variability, glycemic stability and time-in-target (>=70 to <=140mg/dL). RESULTS: The 40 patients (26 on insulin pump) were aged 24+/-5 years and BMI 24.5+/-3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0+/-0.9% to 7.6+/-0.9%, p<0.0001), normalized AUCTOTAL CGM decreased from 153.7+/-25.4 to 149.0+/-30.2mg/dL?h at end-of-treatment (p = 0.31), and significantly increased post-treatment (164.1+/-29.5mg/dL?h, p = 0.02). The numerical decrease in normalized AUCNIGHT (152.0+/-36.6 to 141.9+/ 34.4mg/dL?h, p = 0.13) exceeded AUCDAY (154.5+/-24.5 to 152.6+/-30.4mg/dL?h, p = 0.65). Trends toward lower glycemic variability (83.1+/-18.9 to 75.6+/-28.6mg/dL, p = 0.06) and little change in glycemic stability (10.8+/-3.6 to 10.3+/ 4.5mg/dL/h, p = 0.51) were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3+/-19.3mg/dL, p = 0.04 and 11.8+/-3.7mg/dL/hr, p = 0.08). Time-in-target numerically increased (40.2+/-11.9 to 43.1+/-13.5%, p = 0.69) at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects. CONCLUSIONS: We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime. TRIAL REGISTRATION: Clinicaltrials.gov NCT01392560. PMID- 26544193 TI - Human Salivary Micro-RNA in Patients with Parotid Salivary Gland Neoplasms. AB - BACKGROUND: Currently, clinical examination, ultrasound scanning (with or without fine needle aspiration cytology), preoperative CT-scan and MRI are available for the differential diagnosis of parotid gland swelling. A preliminary non-invasive salivary diagnostic tool may be helpful in the clinical decision making process. Altered salivary micro-RNA (miRNA) expression levels have been observed in saliva from patients with various cancers. Therefore, we investigated miRNA expression levels in saliva samples from patients with a parotid gland neoplasm using Human miRNA cards in comparison to controls. RESULTS: In the discovery phase, eight miRNAs were identified having different expression levels in patients compared to controls. In the validation phase, the differences in miRNA expression levels between patients and controls were confirmed for seven out of eight discovered miRNAs (p < 0.001). A combination of two miRNAs yielded a receiver-operator characteristics curve with an AUC of 0.94 (95% CI: 0.87-1.00; sensitivity 91%; specificity 86%). Validation of discovered miRNAs in segregated collected parotid saliva revealed that expression of these miRNAs differ between whole saliva and parotid saliva. CONCLUSIONS: A two miRNA combination can predict the presence of a parotid gland neoplasm. Furthermore, this study suggested that the identified, patient-specific, salivary miRNAs were not derived from the parotid gland itself. PMID- 26544194 TI - Management of the Metabolic Syndrome and the Obese Patient with Metabolic Disturbances: South Asian Perspective. AB - There is an increased prevalence of obesity and the metabolic syndrome (MS) among South Asians. The phenotypes of obesity and body fat distribution are different in South Asians; they have high body fat, intra-abdominal and subcutaneous fat and fatty liver at a lower body mass index compared to white Caucasians; this has led to the frequent occurrence of morbidities related to a higher magnitude of adiposity [e.g. type 2 diabetes mellitus (T2DM), hypertension (HTN) and dyslipidemia]. The increasing prevalence of obesity and related diseases in the South Asian population requires aggressive lifestyle management including diet, physical activity and, sometimes, drugs. For therapeutic interventions, several drugs can be used either as mono- or combination therapy. Drugs like orlistat, which is used for the management of obesity, also reduce the risk of T2DM. Similarly, HMG CoA reductase inhibitors decrease low-density-lipoprotein cholesterol levels and reduce the risk of cardiovascular diseases. However, some drugs used for the treatment of HTN (e.g. beta-blockers) may increase the risk of hyperglycemia and therefore need to be used with caution. Finally, to prevent obesity, MS and T2DM among South Asians, it is particularly important to effectively implement and strengthen population-based primary prevention strategies. PMID- 26544195 TI - GalR Acts as a Transcriptional Activator of galKT in the Presence of Galactose in Streptococcus pneumoniae. AB - We explored the regulatory mechanism of Leloir pathway genes in Streptococcus pneumoniae D39. Here, we demonstrate that the expression of galKT is galactose dependent. By microarray analysis and quantitative RT-PCR, we further show the role of the transcriptional regulator GalR, present upstream of galKT, as a transcriptional activator of galKT in the presence of galactose. Moreover, we predict a 19-bp regulatory site (5'-GATAGTTTAGTAAAATTTT-3') for the transcriptional regulator GalR in the promoter region of galK, which is also highly conserved in other streptococci. Growth comparison of D39 DeltagalK with the D39 wild type grown in the presence of galactose shows that galK is required for the proper growth of S. pneumoniae on galactose. PMID- 26544196 TI - A Case of Wiedemann-Steiner Syndrome Associated with a 46,XY Disorder of Sexual Development and Gonadal Dysgenesis. AB - We report the case of a female patient suffering from a 46,XY disorder of sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence of these 2 conditions has not yet been reported. Using whole exome sequencing and comparative genome hybridization array, we identified a de novo MLL/KMT2A gene nonsense mutation which explains the WDSTS phenotype. In addition, we discovered novel genetic variants, which could explain the testicular dysgenesis observed in the patient, a maternally inherited 167-kb duplication of DAAM2 and MOCS1 genes and a de novo LRRC33/NRROS gene mutation. These genes, some of which are expressed during mouse gonadal development, could be considered as potentially new candidate genes for DSD. PMID- 26544198 TI - Human mesenchymal stem cells alter the gene profile of monocytes from patients with Type 2 diabetes and end-stage renal disease. AB - AIM: Macrophage infiltration contributes to the pathogenesis of Type 2 diabetes. Mesenchymal stem cells (MSCs) possess immunomodulatory properties, making them an ideal candidate for therapeutic intervention. This study investigated whether MSCs can modulate the phenotype of monocytes isolated from Type 2 diabetic patients with end-stage renal disease. MATERIALS & METHODS: Monocytes from control (n = 4) and Type 2 diabetic patients with end-stage renal disease (n = 5) were assessed using flow cytometry and microarray profiling, following 48 h of co culture with MSCs. RESULTS: Control subjects had a greater proportion of CD14(++)CD16(-) monocytes while diabetic patients had a higher proportion of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes. MSCs promoted the proliferation of monocytes isolated from diabetic patients, reduced HLA-DR expression in both groups and promoted the expression of anti-inflammatory genes. CONCLUSION: MSC derived factors alter the polarization of monocytes isolated from healthy and diabetic subjects toward an M2 phenotype. PMID- 26544197 TI - Differential Effects of C1qa Ablation on Glaucomatous Damage in Two Sexes in DBA/2NNia Mice. AB - PURPOSE: To determine the sex and age-related effects of C1qa ablation on retinal ganglion cell (RGC) and optic nerve (ON) axonal loss in a mouse model of glaucomatous neurodegeneration. METHODS: Congenic C1qa mice were generated in the DBA/2NNia background. Female and male knockout (-/-), heterozygous (+/-), and wild type (+/+) mice were aged up to 14 months and IOPs were recorded in a subset of animals. Retinas of mice from all three groups at 5-6, 9-10 and 11-13 months of age were flat-mounted after retrograde labeling with Fluorogold. Imaged retinas were scored (RGC score) semi-quantitatively on a 10 point scale by two independent observers. A subset of retinas and optic nerves were also used for measurement of total number of RGCs. Semi-thin sections of ON were imaged and graded (ON score) for the amount of axonal damage semi-quantitatively, by two masked observers. Analysis of covariance (ANCOVA) was used for statistical comparisons. Microglial cells in flat-mounted retinas of 5-6 month old C1qa -/- and C1qa +/+ mice were used for assessment of microglial activation utilizing morphological criteria. RESULTS: Female C1qa -/- mice had significantly higher IOP (p<0.000001, ANOVA) between 8 and 13 months of age compared to C1qa +/+ animals. No differences in IOPs between animals of the three genotypes were observed in males. At 5-6 months of age, there was no difference in RGC or ON scores between the three genotypes in animals of either sex. At 9-10 months of age, female mice didn't show significant differences in RGC or ON scores between the three genotypes. However, male C1qa -/- and C1qa +/- mice of the same age had better RGC and ON scores (p<0.003 and p<0.05, ANCOVA, for RGC and ON scores, respectively) compared with C1qa +/+ mice. At 11-13 months of age, female C1qa -/ mice had better RGC scores (p<0.006, ANCOVA) compared to C1qa +/+ and C1qa +/- animals. Accordingly, C1qa -/- mice had higher RGC counts (p<0.03, t-test) compared to C1qa +/+ animals. In male mice, there was a tendency for 12 month old C1qa -/- animals to have better RGC scores and higher RGC counts, but this didn't reach statistical significance. ON scores in 11-13 month old animals of either sex were not different between all three genotype. Microglial activation in male 5-6 month old C1qa -/- mice was decreased compared to C1qa +/+ animals; no such effect was seen in females. CONCLUSIONS: Absence of C1qa ameliorates RGC and ON loss in the DBA/2NNia strain, but this effect differs between the two sexes. C1q mediated RGC damage seems to be more potent than IOP-mediated RGC loss. In contrast, C1qa absence provides axonal protection early on, but this protection cannot overcome the effects of significant IOP elevation. PMID- 26544199 TI - Combining Computational and Social Effort for Collaborative Problem Solving. AB - Rather than replacing human labor, there is growing evidence that networked computers create opportunities for collaborations of people and algorithms to solve problems beyond either of them. In this study, we demonstrate the conditions under which such synergy can arise. We show that, for a design task, three elements are sufficient: humans apply intuitions to the problem, algorithms automatically determine and report back on the quality of designs, and humans observe and innovate on others' designs to focus creative and computational effort on good designs. This study suggests how such collaborations should be composed for other domains, as well as how social and computational dynamics mutually influence one another during collaborative problem solving. PMID- 26544201 TI - Correction: Whole Grain Intakes in the Diets Of Malaysian Children and Adolescents - Findings from the MyBreakfast Study. PMID- 26544200 TI - MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice. AB - NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs. PMID- 26544202 TI - Pharmacist-Led Medication Reviews to Identify and Collaboratively Resolve Drug Related Problems in Psychiatry - A Controlled, Clinical Trial. AB - AIM OF THE STUDY: This prospective, controlled trial aimed to assess the effect of pharmacist-led medication reviews on the medication safety of psychiatric inpatients by the resolution of Drug-Related Problems (DRP). Both the therapy appropriateness measured with the Medication Appropriateness Index (MAI) and the number of unsolved DRP per patient were chosen as primary outcome measures. METHODS: Depending on their time of admission, 269 psychiatric patients that were admitted to a psychiatric university hospital were allocated in control (09/2012 03/2013) or intervention group (05/2013-12/2013). In both groups, DRP were identified by comprehensive medication reviews by clinical pharmacists at admission, during the hospital stay, and at discharge. In the intervention group, recommendations for identified DRP were compiled by the pharmacists and discussed with the therapeutic team. In the control group, recommendations were not provided except for serious or life threatening DRP. As a primary outcome measure, the changes in therapy appropriateness from admission to discharge as well as from admission to three months after discharge (follow-up) assessed with the MAI were compared between both groups. The second primary outcome was the number of unsolved DRP per patient after completing the study protocol. The DRP type, the relevance and the potential of drugs to cause DRP were also evaluated. RESULTS: The intervention led to a reduced MAI score by 1.4 points per patient (95% confidence interval [CI]: 0.8-2.0) at discharge and 1.3 points (95% CI: 0.7 1.9) at follow-up compared with controls. The number of unsolved DRP in the intervention group was 1.8 (95% CI: 1.5-2.1) less than in control. CONCLUSION: The pharmaceutical medication reviews with interdisciplinary discussion of identified DRP appears to be a worthy strategy to improve medication safety in psychiatry as reflected by less unsolved DRP per patient and an enhanced appropriateness of therapy. The promising results of this trial likely warrant further research that evaluates direct clinical outcomes and health-related costs. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS), DRKS00006358. PMID- 26544204 TI - Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG. AB - Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTATM. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation. PMID- 26544203 TI - Cost Effectiveness of Daclatasvir/Asunaprevir Versus Peginterferon/Ribavirin and Protease Inhibitors for the Treatment of Hepatitis c Genotype 1b Naive Patients in Chile. AB - INTRODUCTION: Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources. METHODS: A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$ 16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$ 6,375/QALY at a price of US$ 38,710; and US$ 1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$ 38,710 was 91.6% while there is a 21.43% probability that DCV/ASV dominates PR if the total treatment price was US$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita. CONCLUSIONS: DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system. PMID- 26544205 TI - Fungal dissemination by housefly (Musca domestica L.) and contamination of food commodities in rural areas of South Africa. AB - Several insects that act as vectors, including houseflies (Musca domestica L.), are often considered to be an important source of fungal contamination in human foods. Houseflies are also involved in the transmission of bacterial pathogens that may pose a serious hazard to human health. Thus, the rural population of South Africa, as typified by that in the Gauteng Province investigated in this study, is at high risk from fungal exposure disseminated by houseflies and it is therefore important to assess the role of flies in contaminating various food commodities. Eighty four samples of houseflies (captured from households and pit toilets) were studied for their potential to carry fungal spores into food commodities. The fungi occurring in samples of raw maize (15) and porridge (19) were also assessed. Fungal isolates were identified based on morphological characteristics by conventional identification methods. Fifteen genera of fungi were isolated and identified, of which Aspergillus, Fusarium, Penicillium, Cladosporium, Moniliella and Mucor were the most prevalent in all three sample types analysed. The incidence rates of fungal contamination per total fungal count isolated in houseflies, maize and porridge were recorded with mean fungal load of 2*10(8) CFU/ml, 1*10(7)CFU/g and 2*10(7)CFU/g respectively. Additionally, A. flavus, A. parasiticus, F. verticillioides, F. proliferatum, P. verrucosum, P. aurantiogriseum and M. suaveolens were the most frequent fungal isolates in houseflies with incidence rate of 34%, 11%, 27%, 21%, 22%, 17% and 32% respectively. F. verticillioides, A. flavus, A. niger and P. oslonii were the most prevalent species contaminating porridge and maize with incidence rate of 23%, 32%, 16% and 28% in maize samples, while incidence rates of 59%, 15% and 29% were recorded in porridge samples with the exception of F. verticillioides. The prevalence of these genera of fungi may pose serious health risks. PMID- 26544206 TI - [Not Available]. PMID- 26544207 TI - [Not Available]. PMID- 26544208 TI - [Not Available]. PMID- 26544209 TI - [Not Available]. PMID- 26544210 TI - [Not Available]. PMID- 26544211 TI - [Not Available]. PMID- 26544212 TI - [Not Available]. PMID- 26544213 TI - [Not Available]. PMID- 26544214 TI - [Not Available]. PMID- 26544215 TI - [Not Available]. 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PMID- 26544243 TI - Durable improvements in urinary incontinence and positive treatment response in patients with idiopathic overactive bladder syndrome following long-term onabotulinumtoxinA treatment: Final results of 3.5-year study. AB - OBJECTIVES: Here we present the final results from an extension study assessing long-term onabotulinumtoxinA treatment (3.5 years) in patients with idiopathic overactive bladder. METHODS: Patients who completed either of 2 Phase III trials were eligible to enter a 3-year extension study in which they received multiple onabotulinumtoxinA (100 U) treatments. Data were analyzed for the overall population of patients who received 100 U in any treatment cycle (n=829) and within discrete subgroups of patients who received exactly 1 (n=105), 2 (n=118), 3 (n=117), 4 (n=83), 5 (n=46), or 6 (n=33) treatments of the 100 U dose throughout the study (n=502). RESULTS: Of the 829 patients enrolled, 51.7 % completed the study. Discontinuations due to AEs/lack of efficacy were low (5.1/5.7 %); other reasons were not treatment-related. Mean reductions from baseline in urinary incontinence (UI) episodes/day (week 12; co-primary endpoint) were consistent among discrete subgroups who received 1 (-3.1), 2 (-2.9, -3.2), 3 (-4.1 to -4.5), 4 (-3.4 to -3.8), 5 (-3.0 to -3.6), or 6 (-3.1 to -4.1) treatments. A consistently high proportion of patients reported improvement/great improvement on the Treatment Benefit Scale (week 12; co-primary endpoint) in the discrete subgroups across all treatments (70.0-93.5 %). Median time to request retreatment was <=6 months for 34.2 %, >6-<=12 months for 37.2 %, and >12 months for 28.5 % of patients. Most common AE was UTI, with no changes in safety profile over time. CONCLUSION: Long-term onabotulinumtoxinA treatment resulted in consistent reductions in UI and high proportions of patients reporting improvement after each treatment, with no new safety findings. 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The molecular interactions that regulate this chemistry are not fully elucidated, therefore we address this issue by investigating one part of the active site that may control this reaction. Here, the effects of the 2,4-heme substituents on the nitrite reductase (NiR) reaction, and on the structures and energies of the ferrous nitrite intermediates, are investigated using Mb as a model system. This is accomplished by studying Mbs with hemes that have different 2,4-R groups, namely diacetyldeuteroMb (-acetyl), protoMb (wild-type (wt) Mb, -vinyl), deuteroMb (-H), and mesoMb (-ethyl). While trends on the natural charge on Fe and O-atom of bound nitrite are observed among the series of Mbs, the Fe(II)-NPyr (Pyr=pyrrole) and Fe(II)-NHis93 (His=histidine) bond lengths do not significantly change. Kinetic analysis shows increasing NiR activity as follows: diacetyldeuteroMb60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56(bright) and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16+ NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance. PMID- 26544513 TI - Mutant HRAS as novel target for MEK and mTOR inhibitors. AB - HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an impact on viability. However, inhibition of mTOR or combined inhibition of MEK and mTOR reduced cell growth in a synergistic manner. Finally, Ba/F3 cells transformed with mutant HRAS isoforms Q61L, Q61R and G12V demonstrated equal sensitivity towards MEK and mTOR inhibition. Our results show that HRAS mutations in cancer activate the RAS and mTOR pathways which might serve as a therapeutic option for patients with HRAS mutant tumors. PMID- 26544514 TI - Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation. AB - Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologically confirmed glioma. The kurtosis and conventional diffusion metric values of the tumor were semi-automatically obtained. The relationships of these metrics with the glioma grade and Ki-67 expression were evaluated. The diagnostic efficiency of these metrics in grading was further compared. It was demonstrated that compared with the conventional diffusion metrics, the kurtosis metrics were more promising imaging markers in distinguishing high-grade from low-grade gliomas and distinguishing among grade II, III and IV gliomas; the kurtosis metrics also showed great potential in the prediction of Ki-67 expression. To our best knowledge, we are the first to reveal the ability of DKI to assess the cellular proliferation of gliomas, and to employ the semi-automatic method for the accurate measurement of gliomas. These results could have a significant impact on the diagnosis and subsequent therapy of glioma. PMID- 26544516 TI - The Impact of Resident Duty Hour and Supervision Changes: A Review. AB - In 2003 and again in 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted increasingly stringent requirements governing resident hours and supervision, with the goals of improving patient safety, resident well-being, and resident education. Although the changes initially stemmed from a catastrophic outcome in a patient treated with psychotropic medications and behavioral restraints, and have been in place over a decade, many psychiatrists are not familiar with these changes and with their potential effects and "side effects" on today's trainees and faculty. The authors review the history leading to these changes, summarize the revised requirements, and review representative literature regarding the impact of the changes. The existing studies of the impact of the new requirements on improving patient safety, resident well-being, and resident education are inconclusive, and most editorials, perspectives, and surveys of faculty and residents reflect a lack of enthusiasm for the changes. They go on to suggest the need for evidence-based outcome studies prior to the institution of further major changes in ACGME requirements. PMID- 26544515 TI - Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. AB - PURPOSE: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. METHODS: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. RESULTS: RT PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4 ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. CONCLUSIONS: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. PMID- 26544517 TI - The fate of MtBE during Fenton-like treatments through laboratory scale column tests. AB - In Situ Chemical Oxidation (ISCO) based on the Fenton's process is a proven technology for the treatment of groundwater contaminated by organic compounds. Nevertheless, the application of this treatment process to methyl tert-butyl ether (MtBE) is questioned, as there are concerns about its capacity to achieve complete mineralization. Many existing studies have focused on water contaminated by MtBE and are thus not representative of in situ treatments since they do not consider the presence of soil. In this work, the effectiveness of a Fenton-like process for MtBE treatment was proven in soil column tests performed at operating conditions (i.e., oxidant and contaminant concentration and flow rates) resembling those typically used for in situ applications. No MtBE by-products were detected in any of the tested conditions, thus suggesting that the tert butyl group of MtBE was completely degraded. A mass balance based on the CO2 produced was used as evidence that most of the MtBE removed was actually mineralized. Finally, the obtained results show that preconditioning of soil with a chelating agent (EDTA) significantly enhanced MtBE oxidation. PMID- 26544520 TI - [In Process Citation]. PMID- 26544518 TI - Ameliorative effects of thymoquinone against eye lens changes in streptozotocin diabetic rats. AB - The possible protective effect of thymoquinone against eye lens changes in diabetic rats was investigated. Following diabetes induction by a single injection of streptozotocin (45 mg/kg, i.p.), thymoquinone was administered in three different doses (20, 40, and 80 mg/kg/day, p.o.) for 12 weeks. Thymoquinone significantly and dose-dependently attenuated the hypoinsulinemia and hyperglycemia in diabetic rats. Also, thymoquinone (particularly 40 and 80 mg/kg) significantly decreased the elevations of malondialdehyde, nitric oxide, tumor necrosis factor-alpha, glycated proteins, aldose reductase activity, sorbitol level, and caspase-3 activity in the lens tissues of diabetic rats. In addition, thymoquinone (particularly 40 and 80 mg/kg) significantly ameliorated the diabetes-induced reductions of glutathione peroxidase, superoxide dismutase, and catalase activities, and total and soluble protein contents in the lens tissues. It was concluded that thymoquinone significantly protected the lens tissue against changes induced by diabetes in rats through its antioxidant, anti inflammatory, and antidiabetic effects. PMID- 26544522 TI - Automated interpretation of home blood pressure assessment (Hy-Result software) versus physician's assessment: a validation study. AB - OBJECTIVE: Hy-Result is the first software for self-interpretation of home blood pressure measurement results, taking into account both the recommended thresholds for normal values and patient characteristics. We compare the software-generated classification with the physician's evaluation. DESIGN METHOD: The primary assessment criterion was whether algorithm classification of the blood pressure (BP) status concurred with the physician's advice (blinded to the software's results) following a consultation (n=195 patients). Secondary assessment was the reliability of text messages. RESULTS: In the 58 untreated patients, the agreement between classification of the BP status generated by the software and the physician's classification was 87.9%. In the 137 treated patients, the agreement was 91.9%. The kappa-test applied for all the patients was 0.81 (95% confidence interval: 0.73-0.89). After correction of errors identified in the algorithm during the study, agreement increased to 95.4% [kappa=0.9 (95% confidence interval: 0.84-0.97)]. For 100% of the patients with comorbidities (n=46), specific text messages were generated, indicating that a physician might recommend a target BP lower than 135/85 mmHg. Specific text messages were also generated for 100% of the patients for whom global cardiovascular risks markedly exceeded norms. CONCLUSION: Classification by Hy-Result is at least as accurate as that of a specialist in current practice (http://www.hy-result.com). PMID- 26544523 TI - Validation of the Andon KD595 for clinical use and self-measurement according to the European Society of Hypertension International Protocol. AB - This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure monitor Andon KD595 for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were sequentially measured in 33 participants using the standard mercury sphygmomanometer and the Andon KD595 device. Ninety-nine pairs of comparisons were obtained from 33 participants for analysis. The KD595 device achieved the targets in part 1 of the validation study. The number of absolute differences between the device and the observers within a range of 5, 10, and 15 mmHg was 72/99, 93/99, and 96/99, respectively, for SBP and 72/99, 96/99, and 99/99, respectively, for DBP. The device also achieved the targets in part 2 of the validation study. A total of 28 and 25 participants had at least two of the three device-observer differences within 5 mmHg (required>=24) for SBP and DBP, respectively. The number of participants without device-observer difference within 5 mmHg was two for SBP and two for DBP (required<=3). The Andon upper arm blood pressure monitor KD595 has passed the International Protocol requirements and it can be recommended for clinical use and self-measurement in adults. PMID- 26544524 TI - Spontaneous blood pressure oscillations in mechanically ventilated patients with sepsis. AB - OBJECTIVE: In the present hypothesis-generating study, we investigated whether spontaneous blood pressure oscillations are suppressed to lower frequencies, and whether abolished oscillations are associated with an adverse outcome in mechanically ventilated patients with sepsis. METHODS: We retrospectively subjected invasive steady-state blood pressure recordings from 65 mechanically ventilated patients with sepsis to spectral analysis. Modified spectral bands were visually identified by plotting spectral power against frequency. RESULTS: Modified middle-frequency and low-frequency (MF' and LF') oscillations were absent in 9% and 22% of the patients, respectively. In patients in whom spontaneous blood pressure oscillations were preserved, the MF' oscillations occurred at 0.021 Hz (median, interquartile range 0.013-0.030), whereas the LF' oscillations occurred at 0.009 Hz (median, interquartile range 0.006-0.010). The absence of LF' oscillations was associated with a higher 30-day mortality [50 vs. 18%, hazard ratio, 3.6 (95% confidence interval: 1.4-9.8), P=0.01]. CONCLUSION: Spontaneous blood pressure oscillations in mechanically ventilated septic patients may be suppressed to lower frequencies than previously reported for spontaneously breathing, healthy humans. Patients in whom the resultant changes in blood pressure (MF' and LF' oscillations) are abolished may have a higher risk of an adverse outcome. This may reflect suppression of the pressor area in the brainstem with subsequent sympathetic dysfunction. PMID- 26544525 TI - Is renal denervation an effective treatment for hypertension? Comparison of recent meta-analysis and a multinational registry. AB - We compared the impact of renal denervation (RDN) on blood pressures using results available from a recent comprehensive meta-analysis and an international registry. The meta-analysis summarized recent trials in which RDN was compared with control groups that were treated only with antihypertensive medication; the registry only included patients treated with RDN. Both publications presented pretreatment pressures and changes 6 months postbaseline. Significant reductions in office systolic pressure and 24 h ambulatory systolic pressure were observed in both groups of the meta-analysis and the registry. However, the magnitude of blood pressure reduction with RDN and medical treatment was comparable in both the meta-analysis and registry. RDN has not been shown to be superior to medical management of hypertension in this combined experience of nearly 2000 hypertensive patients. PMID- 26544526 TI - Assessment of selective motor control in clinical Gillette's test using electromyography. AB - BACKGROUND: Selective motor control (SMC), the ability to isolate selected muscle activation during a functional task, is often impaired. Gillette's SMC scale is commonly used to classify the impairment level; however it may not be sensitive to muscle coactivation. AIM: To characterize differences in muscle activation levels and coactivation incidence in Gillette's SMC grade levels. DESIGN: Non randomized observational study. SETTING: Participants were recruited and examined in the motion analysis laboratory of a university hospital. POPULATION: Forty-two participants were enrolled: 23 patients with CP (13 females, 10 males; 15+/-5.59 years, range: 7-28 years; bilateral involvement; GMFCS levels I to III) and 19 able-bodied volunteers (14 females, 5 males; 22+/-1.54 years, range: 20-24 years). METHODS: Participants flexed each knee three times at self-paced velocity. Each limb was classified into one of three types using Gillette's SMC scale: Type 0 (CP limbs with no ability to isolate movement), Type 2 (CP limbs with complete isolation of movement) and Type C (Control limbs of able-bodied volunteers). Surface electromyography recorded muscle activation levels of hamstring, rectus femoris, hip adductor, gastrocnemius and tibialis anterior muscles. We applied the Friedman ANOVA chi2 Test to analyze muscle co-activation incidence and Kruskal-Wallis ANOVA and Median Tests to analyze muscle activation levels. We used the Wilcoxon Matched-Pairs Test to compare results between SMC Types. RESULTS: Comparing mean activation levels of the majority of muscles, we found: CP limbs (Type 0+2) > Control limbs (P<0.001); Type 0 > Type 2 (P<0.05); and Type 2 > Type C (P<0.01). The incidence of muscle co-activation was affected by CP (P=0.008) and differed by SMC type (P<0.001). CONCLUSIONS: Our quantitative study confirmed that SMC is worse in Gillette's Type 0 limbs than in Type 2 limbs. We also found that the SMC of Type 2 limbs of CP patients in CP patents is not equivalent to that of Type 2 limbs in able-bodied volunteers. CLINICAL REHABILITATION IMPACT: A better characterization of this clinical test will help gauge its usefulness in evaluating the effectiveness of rehabilitation treatments. PMID- 26544527 TI - Studies on Tris(2-aminobenzimidazole)-PNA Based Artificial Nucleases: A Comparison of Two Analytical Techniques. AB - A new peptide nucleic acid (PNA) construct carrying a tris(2-aminobenzimidazole) phosphodiester cleaver is presented. This non-metal-based artificial nuclease hydrolyzes RNA substrates that form a bulge upon binding to the PNA. Reaction rates depend on the bulge sequence. For conjugates of tris(2-aminobenzimidazole), substrate turnover is shown for the first time. Two methods of analysis for the kinetics are compared: IE-HPLC separation of oligonucleotide fragments and analysis of Cy5-labeled oligonucleotide fragments by denaturating PAGE on a DNA sequencer, respectively. The different methods give rates that are in the same range where, in general, the substrates for the sequencer method give slightly lower rates. PMID- 26544528 TI - Uranium(VI) Scavenging by Amorphous Iron Phosphate Encrusting Sphaerotilus natans Filaments. AB - U(VI) sorption to iron oxyhydroxides, precipitation of phosphate minerals, as well as biosorption on bacterial biomass are among the most reported processes able to scavenge U(VI) under oxidizing conditions. Although phosphates significantly influence bacterially mediated as well as iron oxyhydroxide mediated scavenging of uranium, the sorption or coprecipitation of U(VI) with poorly crystalline nanosized iron phosphates has been scarcely documented, especially in the presence of microorganisms. Here we show that dissolved U(VI) can be bound to amorphous iron phosphate during their deposition on Sphaerotilus natans filamentous bacteria. Uranium LIII-edge EXAFS analysis reveals that the adsorbed uranyl ions share an equatorial oxygen atom with a phosphate tetrahedron of the amorphous iron phosphate, with a characteristic U-P distance of 3.6 A. In addition, the uranyl ions are connected to FeO6 octahedra with U-Fe distances at ~3.4 A and at ~4.0 A. The shortest U-Fe distance corresponds to a bidentate edge sharing complex often reported for uranyl adsorption onto iron oxyhydroxides, whereas the longest U-Fe and U-P distances can be interpreted as a bidentate corner-sharing complex, in which two adjacent equatorial oxygen atoms are shared with the vertices of a FeO6 octahedron and of a phosphate tetrahedron. Furthermore, based on these sorption reactions, we demonstrate the ability of an attached S. natans biofilm to remove uranium from solution without any filtration step. PMID- 26544529 TI - Diastereoselective Total Synthesis of (-)-Galiellalactone. AB - An enantioselective total synthesis of (-)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the cis-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (-) galiellalactone via a combination of diastereoselective Hosomi-Sakurai crotylation and ring-closing metathesis (RCM). PMID- 26544530 TI - Complete mitochondrial genome of Stummer's Racerunner (Eremias stummeri) from Kazakhstan. AB - The whole mitochondrial genome was determined from a viviparous racerunner, Eremias stummeri, which was collected from southeast Kazakhstan. The mitogenome sequence was 19 602 bp in size, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a control region, which is similar to the typical mtDNA of vertebrates. Mitochondrial genomes analyses using maximum parsimony and Bayesian analyses yielded identical phylogenetic trees, indicating a close phylogenetic affinity of the sampled taxa in genus Eremias. Monophyly of both Eremias and its viviparous group is recovered. The complete mitogenome sequence of E. stummeri provides fundamental data for resolving phylogeneitc and genetic problems related to Eremias viviparity. PMID- 26544532 TI - The Power of the Virtual Ideal Self in Weight Control: Weight-Reduced Avatars Can Enhance the Tendency to Delay Gratification and Regulate Dietary Practices. AB - The tendency to discount larger future benefits in favor of smaller immediate gains (i.e., temporal discounting) is relevant to the issue of obesity. Successful weight loss requires individuals to sacrifice immediate culinary pleasures in favor of future health gains. Based on the notion that increasing the vividness of one's future self may mitigate temporal discounting and promote the ability to delay gratification, we examined whether viewing one's weight reduced self (i.e., the ideal self) in a virtual environment can decrease temporal discounting and lead to better regulation of dietary practices. Seventy six undergraduates who had reported an intention to lose weight were recruited to participate in a laboratory experiment and were randomly assigned to interact with either the weight-reduced self (experimental condition) or the present self (control condition) by looking into a dressing mirror in a virtual fitting room. A temporal-discounting task and a taste test were subsequently administered. Results showed that, compared with control participants, participants who viewed their weight-reduced avatars ate less ice cream in a taste test and were more likely to choose a sugar-free drink as a reward. The discounting rate mediated the association between the avatar manipulation and the amount of ice cream eaten in the subsequent taste test. Overall, our findings suggest that a computer generated image of one's weight-reduced self may assist in resisting impulses that promote immediate gratification over delayed benefits. This research provides a new approach for controlling impulsive behavior such as dietary regulation and weight control. PMID- 26544534 TI - Notice of Retraction: Ramipril Markedly Improves Walking Ability in Patients With Peripheral Arterial Disease [Summary for Patients]. PMID- 26544533 TI - Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity. AB - BACKGROUND: Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with cafe au lait spots and axillary freckling mimicking neurofibromatosis type 1. PROCEDURE: We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer. RESULTS: In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified. CONCLUSIONS: CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis. PMID- 26544535 TI - A Telerehabilitation Approach for Chronic Aphasia Following Stroke. AB - BACKGROUND: Intensive speech therapy improves language function in patients with chronic aphasia, although treatment in the acute phase is more effective than in the chronic phase. Unfortunately, most patients with stroke go untreated due to socioeconomic problems. This study was performed to develop and test a speech therapy-based telerehabilitation program (iAphasia), suitable for use on a mobile device platform, which would expand access to therapy to patients who frequently go untreated. SUBJECTS AND METHODS: We enrolled 8 patients with chronic poststroke aphasia to receive therapy via our iPad((r)) (Apple, Cupertino, CA) based telespeech therapy program, iAphasia. Participants received 4 weeks of telespeech therapy using iAphasia, which generates six domains with six levels of difficulty. We compared pre- and posttreatment scores on the Korean version of the Western Aphasia Battery (K-WAB) to evaluate effectiveness. Additionally, a 1 month follow-up assessment was performed. RESULTS: We investigated user satisfaction using a questionnaire to assess the feasibility of iAphasia. After the 4-week treatment, language function as measured by the K-WAB improved significantly. The improvement was persistent at the 1-month follow-up visit. The degree of improvement was strongly associated with usage time, regardless of participants' age and severity of aphasia. Overall, satisfaction with iAphasia was rated high. CONCLUSIONS: The results from this study suggest it to be an effective and feasible treatment method for chronic aphasia, although follow-up studies with more subjects and a control group are needed for a more thorough assessment. PMID- 26544537 TI - Quantifying Epithelial Early Common Progenitors from Long-Term Primary or Cell Line Sphere Culture. AB - Here, a protocol to quantify epithelial early common progenitor/stem cells grown as spheres in non-adherent culture conditions is described. This protocol is based on the combination of two functional tests: the sphere assay to maintain and enrich early progenitor/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated. Spheres are enzymatically and mechanically dissociated; the derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for further processing, as in the E-CFC assay. The principle of this assay is to quantify the number of epithelial colonies generated by cells present in the different sequential spheres. This assay has therefore been named the early common progenitor-derived colonies assay (ECP-DC). PMID- 26544536 TI - Long non-coding RNA urothelial cancer-associated 1 promotes bladder cancer cell migration and invasion by way of the hsa-miR-145-ZEB1/2-FSCN1 pathway. AB - Numerous studies suggest that several long non-coding RNAs (lncRNAs) play critical roles in bladder cancer development and progression. Long non-coding RNA urothelial cancer-associated 1 (lncRNA-UCA1) is highly expressed in bladder cancer tissues and cells, and it has been shown to play an important role in regulating aggressive phenotypes of bladder cancer cells. However, little is known about the molecular mechanism of lncRNA-UCA1-mediated bladder cancer cell migration and invasion. Here, we show that overexpression of lncRNA-UCA1 could induce EMT and increase the migratory and invasive abilities of bladder cancer cells. Mechanistically, lncRNA-UCA1 induced EMT of bladder cancer cells by upregulating the expression levels of zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), and regulated bladder cancer cell migration and invasion by tumor suppressive hsa-miR-145 and its target gene the actin-binding protein fascin homologue 1 (FSCN1). Furthermore, we also observed a positive correlation between lncRNA-UCA1 and ZEB1/2 expression, and a negative correlation between lncRNA-UCA1 and hsa-miR-145 expression in bladder cancer specimens. Importantly, we found that lncRNA-UCA1 repressed hsa-miR-145 expression to upregulate ZEB1/2, whereas the suppression of hsa-miR-145 could upregulate lncRNA-UCA1 expression in bladder cancer cells. Moreover, the binding site for hsa-miR-145 within exons 2 and 3 of lncRNA-UCA1 contributed to the reciprocal negative regulation of lncRNA UCA1 and hsa-miR-145. Taken together, our results identified that lncRNA-UCA1 enhances bladder cancer cell migration and invasion in part through the hsa-miR 145/ZEB1/2/FSCN1 pathway. Therefore, lncRNA-UCA1 might act as a promising therapeutic target for the invasion and metastasis of bladder cancer. PMID- 26544538 TI - The Derivation of Primary Human Epicardium-Derived Cells. AB - To develop therapeutic strategies for the regeneration of lost heart muscle after myocardial infarction (MI), a source of functional new muscle cells and associated coronary vessels must be identified. The epicardium is a source of several cardiovascular cell types during heart development and is widely regarded as a resident progenitor population, which becomes dormant during adulthood. In adult mice, MI induces epicardial reactivation characterized by an upregulation of fetal genes and subsequent epicardium derived cell (EPDC) proliferation, migration, and differentiation. Determining whether the epicardium can be therapeutically targeted following cardiovascular disease requires an in vitro system for the study of adult human EPDCs (hEPDCs). This protocol describes techniques to establish and maintain human epicardium explant cultures from patient-derived right atrial appendage biopsies and documents methods to probe the resultant outgrowth of hEPDCs. The model facilitates a high-throughput approach to either genetic or chemical phenotypic screening for drug-like modifiers of hEPDC activation and potential cell fate. PMID- 26544539 TI - Ethanol for preventing preterm birth in threatened preterm labor. AB - BACKGROUND: Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. OBJECTIVES: To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth < 48 hours after trial entry (one trial, 35 women; risk ratio (RR) 0.93, 95% confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR 1.06, 95% CI 0.31 to 3.58). Serious maternal adverse events and perinatal mortality were not reported by either of the two trials in this comparison. Maternal adverse events (overall) were not reported but one trial (42 women) reported that there were no maternal adverse events that required stopping or changing drug) in either group. One trial did report delay until delivery but this outcome was reported as a median with no mention of the standard deviation (median 19 days in ethanol group versus "less than 1" day in the glucose/water group). There were no differences in any secondary outcomes reported: preterm birth < 34 weeks or < 37 weeks; serious infant outcome; fetal alcohol syndrome/fetal alcohol spectrum disorder; or small-for-gestational age. Comparison 2: Ethanol versus other tocolytic (betamimetics) (nine trials, 1438 women) Compared to betamimetics (the only tocolytic used as a comparator in these studies), ethanol was associated with no clear difference in the rate of birth < 48 hours after trial entry (two trials, 130 women; average RR 1.12, 95% CI 0.53 to 2.37, Tau2 = 0.19, I2 = 59%), similar rates of perinatal mortality (six trials, 698 women; RR1.20, 95% CI 0.78 to 1.84), higher rates of neonatal mortality (eight trials, 1238 women; RR 1.43, 95% CI 1.02 to 2.02), higher rates of preterm birth < 34 weeks (two trials, 599 women; RR 1.56, 95% CI 1.11 to 2.19), higher rates of neonatal respiratory distress syndrome (three trials, 823 women; RR 1.76, 95% CI 1.33 to 2.33), and higher rates of low birthweight babies < 2500 g (five trials, 834 women; RR 1.30, 95% CI 1.09 to 1.54). These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics, which for all these comparisons were betamimetics. Serious maternal adverse events were not reported in any of the nine trial reports. However, ethanol had a trend towards a lower rate of maternal adverse events requiring stopping or changing the drug (three trials, 214 women; RR 0.25, 95% CI 0.06 to 0.97). There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events.Planned sensitivity analysis, excluding quasi-randomized trials did not substantially change the results of the primary outcome analyses with the exception of neonatal mortality which no longer showed a clear difference between the ethanol and other tocolytic groups (3 trials, 330 women; RR 1.49, 95% CI 0.82 to 2.72). AUTHORS' CONCLUSIONS: This review is based on evidence from twelve studies which were mostly low quality. There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo. There is some evidence that ethanol may be better tolerated than other tocolytics (in this case betamimetics), but this result is based on few studies and small sample size and therefore should be interpreted with caution. Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor.Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth in threatened preterm labour. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status. PMID- 26544540 TI - Adiponectin: is it a biomarker for assessing the disease severity in knee osteoarthritis patients? AB - AIM: The results of previous studies regarding the role of adiponectin in the pathogenesis of osteoarthritis (OA) are controversial. The aim of this study is to investigate the relation of plasma adiponectin levels with clinical and radiological disease severity in knee OA patients. METHOD: Sixty patients with knee OA and 25 healthy controls were included in the study. Patients were divided into two subgroups: lean (Group 1, n = 30) and obese (Group 2, n = 30). Healthy controls were accepted as Group 3 (n = 25). Pain intensity was measured with a visual analogue scale (VAS), functional disability with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Quality of Life (QoL) with Short Form-36 (SF-36). Also all patients were radiologically evaluated and graded according to Kellgren-Lawrence (KL) scale. Plasma concentrations of adiponectin levels were measured by enzyme-linked immune-sorbent assay (ELISA). RESULTS: Serum adiponectin levels were higher in OA patient subgroups than those in the control group but the difference did not reach a significant level after adjustments for age, gender and body mass index (P = 0.078). There was a positive correlation between adiponectin concentration and KL grading scores. Additionally, there was a positive correlation between adiponectin levels and clinical variables (VAS and WOMAC total scores) in patient subgroups (r = 0.326 P = 0.012, r = 0.583 P < 0.001, respectively). SF-36 scores were inversely associated with adiponectin levels. CONCLUSION: Plasma adiponectin concentrations were associated with both clinical and radiological disease severity in knee OA patients. Thus, adiponectin hormone might be a potential clinically useful biomarker while assessing disease severity in the future. PMID- 26544541 TI - Isolation, selection and evaluation of antagonistic yeasts and lactic acid bacteria against ochratoxigenic fungus Aspergillus westerdijkiae on coffee beans. AB - In this study, yeasts and lactic acid bacteria (LAB) were isolated from coffee fruits and identified via biochemical and molecular approaches. The isolates represented the Pichia, Debaryomyces, Candida, Clavispora, Yarrowia, Sporobolomyces, Klyveromyces, Torulaspora and Lactobacillus genera. Four isolates, namely Pichia fermentans LPBYB13, Sporobolomyces roseus LPBY7E, Candida sp. LPBY11B and Lactobacillus brevis LPBB03, were found to have the greatest antagonist activity against an ochratoxigenic strain of Aspergillus westerdijkiae on agar tests and were selected for further characterization. Applications of P. fermentans LPBYB13 in coffee cherries artificially contaminated with A. westerdijkiae showed efficacy in reducing ochratoxin A (OTA) content up to 88%. These results highlight that P. fermentans LPBYB13 fulfils the principle requirements of an efficient biological control of aflatoxigenic fungi in coffee beans and may be seen as a reliable candidate for further validation in field conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Studies based on microbial ecology and antagonistic interactions are important for the development of new strategies in controlling aflatoxin contamination of crops and are relevant to further biotechnological applications. This study shows that coffee fruit is a potential source for the isolation of microbial strains with antifungal ability. A new yeast strain, Pichia fermentans LPBYB13, showed efficacy in reducing growth and ochratoxin A production of Aspergillus westerdijkiae in coffee beans. Our results should encourage the use of this yeast strain on a large scale for biocontrol of aflatoxigenic fungi in coffee beans. PMID- 26544542 TI - Pharmacological interventions for unilateral spatial neglect after stroke. AB - BACKGROUND: Unilateral spatial neglect (USN) is characterized by the inability to report or respond to people or objects presented on the side contralateral to the lesioned side of the brain and has been associated with poor functional outcomes and long stays in hospitals and rehabilitation centers. Pharmacological interventions (medical interventions only, use of drugs to improve the health condition), such as dopamine and noradrenergic agonists or pro-cholinergic treatment, have been used in people affected by USN after stroke, and effects of these treatments could provide new insights for health professionals and policy makers. OBJECTIVES: To evaluate the effectiveness and safety of pharmacological interventions for USN after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (April 2015), MEDLINE (1946 to April 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2015), EMBASE (1980 to April 2015), PsycINFO (1806 to April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to April 2015). We also searched trials and research registers, screened reference lists, and contacted study authors and pharmaceutical companies (April 2015). SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) of pharmacological interventions for USN after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias in the included studies and extracted data. MAIN RESULTS: We included in the review two studies with a total of 30 randomly assigned participants. We rated the quality of the evidence as very low as the result of study limitations, small numbers of events, and small sample sizes, with imprecision in the confidence interval (CI). We were not able to perform meta-analysis because of heterogeneity related to the different interventions evaluated between included studies. Very low-quality evidence from one trial (20 participants) comparing effects of rivastigmine plus rehabilitation versus rehabilitation on overall USN at discharge showed the following: Barrage (mean difference (MD) 0.30, 95% confidence interval (CI) -0.18 to 0.78); Letter Cancellation (MD 10.60, 95% CI 2.07 to 19.13); Sentence Reading (MD 0.20, 95% CI -0.69 to 1.09), and the Wundt Jastrow Area Illusion Test (MD -4.40, 95% CI -8.28 to -0.52); no statistical significance was observed for the same outcomes at 30 days' follow-up. In another trial (10 participants), study authors showed statistically significant reduction in omissions in the three cancellation tasks under transdermal nicotine treatment (mean number of omissions 2.93 +/- 0.5) compared with both baseline (4.95 +/- 0.8) and placebo (5.14 +/- 0.9) (main effect of treatment condition: F (2.23) = 11.06; P value < 0.0001). One major adverse event occurred in the transdermal nicotine treatment group, and treatment was discontinued in the affected participant. None of the included trials reported data on several of the prespecified outcomes (falls, balance, depression or anxiety, poststroke fatigue, and quality of life). AUTHORS' CONCLUSIONS: The quality of the evidence from available RCTs was very low. The effectiveness and safety of pharmacological interventions for USN after stroke are therefore uncertain. Additional large RCTs are needed to evaluate these treatments. PMID- 26544543 TI - Chromogenic Assay for Lung Cancer-Related EGFR Exon 19 Hotspot Deletion Mutations. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) deletion mutations are associated with the development of nonsmall-cell lung cancer (NSCLC) and can serve as useful biomarkers. AIM: In the present study, a novel assay for the detection of EGFR hotspot mutations was designed to be highly sensitive and practically false-positive-free to harness the potential of detecting such mutations as biomarkers early in the diagnosis of NSCLC. The new assay draws from the polymerase chain reaction (PCR) for amplification, blue-white screening for initial allele discrimination, and Sanger sequencing for mutation confirmation. RESULTS: Mutant plasmids were mixed with wild-type DNA in ratios from 1:10 to 1:1000, followed by PCR amplification, blue-white screening, and sequencing. Mutants were successfully sequence confirmed for mixtures at ratios of 1:300 and 1:1000, highlighting the assay's high sensitivity and low risk of false-positives due to confirmation by Sanger sequencing. CONCLUSION: With high sensitivity and low false positives, the present assay is appealing as an aid in the early diagnosis of NSCLC through liquid biopsy. The highly customizable nature of the assay provides the possibility of applications in the early diagnosis of other cancer-related genes through nonsense-transformable mutations. PMID- 26544544 TI - Isolated bilateral transverse agenesis of the distal segments of the lower limbs at the level of the knee joint in a human fetus. AB - Congenital limb anomalies occur in Europe with a prevalence of 3.81/1,000 births and can have a major impact on patients and their families. The present study concerned a female fetus aborted at 23 weeks of gestation because she was affected by non-syndromic bilateral absence of the zeugopod (leg) and autopod (foot). Autopsy of the aborted fetus, X-ray imaging, MRI, and histochemical analysis showed that the distal extremity of both femurs was continued by a cartilage-like mass, without joint cavitation. Karyotype was normal. Moreover, no damaging variant was detected by exome sequencing. The limb characteristics of the fetus, which to our knowledge have not yet been reported in humans, suggest a developmental arrest similar to anomalies described in chicks following surgical experiments on the apical ectodermal ridge of the lower limbs. PMID- 26544545 TI - Membrane properties specialize mammalian inner hair cells for frequency or intensity encoding. AB - The auditory pathway faithfully encodes and relays auditory information to the brain with remarkable speed and precision. The inner hair cells (IHCs) are the primary sensory receptors adapted for rapid auditory signaling, but they are not thought to be intrinsically tuned to encode particular sound frequencies. Here I found that under experimental conditions mimicking those in vivo, mammalian IHCs are intrinsically specialized. Low-frequency gerbil IHCs (~0.3 kHz) have significantly more depolarized resting membrane potentials, faster kinetics, and shorter membrane time constants than high-frequency cells (~30 kHz). The faster kinetics of low-frequency IHCs allow them to follow the phasic component of sound (frequency-following), which is not required for high-frequency cells that are instead optimally configured to encode sustained, graded responses (intensity following). The intrinsic membrane filtering of IHCs ensures accurate encoding of the phasic or sustained components of the cell's in vivo receptor potential, crucial for sound localization and ultimately survival. PMID- 26544547 TI - Tuning Electrical Conductivity of Inorganic Minerals with Carbon Nanomaterials. AB - Conductive powders based on Barite or calcium carbonate with chemically converted graphene (CCG) were successfully synthesized by adsorption of graphene oxide (GO) or graphene oxide nanoribbons (GONRs) onto the mineral surfaces and subsequent chemical reduction with hydrazine. The efficient adsorption of GO or GONRs on the surface of Barite and calcium carbonate-based mineral particles results in graphene-wrapped hybrid materials that demonstrate a concentration dependent electrical conductivity that increases with the GO or GONR loading. PMID- 26544548 TI - Cyclo-P3 Complexes of Vanadium: Redox Properties and Origin of the 31P NMR Chemical Shift. AB - The synthesis and characterization of two high-valent vanadium-cyclo-P3 complexes, (nacnac)V(cyclo-P3)(Ntolyl2) (1) and (nacnac)V(cyclo-P3)(OAr) (2), and an inverted sandwich derivative, [(nacnac)V(Ntolyl2)]2(MU2-eta(3):eta(2)-cyclo P3) (3), are presented. These novel complexes are prepared by activating white phosphorus (P4) with three-coordinate vanadium(II) precursors. Structural metrics, redox behavior, and DFT electronic structure analysis indicate that a [cyclo-P3](3-) ligand is bound to a V(V) center in monomeric species 1 and 2. A salient feature of these new cyclo-P3 complexes is their significantly downfield shifted (by ~300 ppm) (31)P NMR resonances, which is highly unusual compared to related complexes such as (Ar[(i)Pr]N)3Mo(cyclo-P3) (4) and other cyclo-P3 complexes that display significantly upfield shifted resonances. This NMR spectroscopic signature was thus far thought to be a diagnostic property for the cyclo-P3 ligand related to its acute endocyclic angle. Using DFT calculations, we scrutinized and conceptualized the origin of the unusual chemical shifts seen in this new class of complexes. Our analysis provides an intuitive rational paradigm for understanding the experimental (31)P NMR spectroscopic signature by relating the nuclear magnetic shielding with the electronic structure of the molecule, especially with the characteristics of metal-cyclo-P3 bonding. PMID- 26544549 TI - A Spacecraft Electrical Characteristics Multi-Label Classification Method Based on Off-Line FCM Clustering and On-Line WPSVM. AB - This paper proposes a novel multi-label classification method for resolving the spacecraft electrical characteristics problems which involve many unlabeled test data processing, high-dimensional features, long computing time and identification of slow rate. Firstly, both the fuzzy c-means (FCM) offline clustering and the principal component feature extraction algorithms are applied for the feature selection process. Secondly, the approximate weighted proximal support vector machine (WPSVM) online classification algorithms is used to reduce the feature dimension and further improve the rate of recognition for electrical characteristics spacecraft. Finally, the data capture contribution method by using thresholds is proposed to guarantee the validity and consistency of the data selection. The experimental results indicate that the method proposed can obtain better data features of the spacecraft electrical characteristics, improve the accuracy of identification and shorten the computing time effectively. PMID- 26544546 TI - Crumbs is an essential regulator of cytoskeletal dynamics and cell-cell adhesion during dorsal closure in Drosophila. AB - The evolutionarily conserved Crumbs protein is required for epithelial polarity and morphogenesis. Here we identify a novel role of Crumbs as a negative regulator of actomyosin dynamics during dorsal closure in the Drosophila embryo. Embryos carrying a mutation in the FERM (protein 4.1/ezrin/radixin/moesin) domain binding motif of Crumbs die due to an overactive actomyosin network associated with disrupted adherens junctions. This phenotype is restricted to the amnioserosa and does not affect other embryonic epithelia. This function of Crumbs requires DMoesin, the Rho1-GTPase, class-I p21-activated kinases and the Arp2/3 complex. Data presented here point to a critical role of Crumbs in regulating actomyosin dynamics, cell junctions and morphogenesis. PMID- 26544550 TI - The Role of Child Health Days in the Attainment of Global Deworming Coverage Targets among Preschool-Age Children. AB - BACKGROUND: Global deworming programs aim to reach 75% of at-risk preschool-age children (pre-SAC) by 2020. The 2013 global pre-SAC deworming coverage initially published by the World Health Organization (WHO) was 23.9%, but this estimate inadequately captured deworming delivered through Child Health Day (CHD) platforms. OBJECTIVE: To update global and regional coverage estimates of pre-SAC deworming in 2013 by supplementing data from the WHO Preventive Chemotherapy and Transmission Control (PCT) databank with national CHD data. METHODS: UNICEF country offices (n = 82) were mailed a questionnaire in July 2014 to report on official national biannual CHD deworming coverage as part of the global vitamin A supplementation coverage reporting mechanism. Coverage data obtained were validated and considered for inclusion in the PCT databank in a collaboration between UNICEF and WHO. Descriptive statistical analyses were conducted to update the number of pre-SAC reached and the number of treatments delivered. RESULTS: Of the 47 countries that responded to the UNICEF pre-SAC deworming questionnaire, 73 data points from 39 countries were considered for inclusion into the WHO PCT databank. Of these, 21 new data points were from 12 countries were newly integrated into the WHO database. With this integration, deworming coverage among pre-SAC increased to 49.1%, representing an increase in the number of children reached and treatments administered from 63.7 million to 130.7 million and 94.7 million to 234.8 million, respectively. The updated databank comprised 98 mass deworming activities conducted in 55 countries, in which 80.4% of the global pre SAC population requiring deworming reside. In all, 57 countries requiring deworming were not yet represented in the database. CONCLUSIONS: With the inclusion of CHD data, global deworming programs are on track to achieving global pre-SAC coverage targets. However, further efforts are needed to improve pre-SAC coverage reporting as well as to sustain and expand deworming delivery through CHDs and other platforms. PMID- 26544552 TI - ATP-Mediated Compositional Change in Peripheral Myelin Membranes: A Comparative Raman Spectroscopy and Time-Of-Flight Secondary Ion Mass Spectrometry Study. AB - In the present paper we addressed a mechanism of the myelin reorganization initiated by extracellular ATP and adenosine in sciatic nerves of the frog Rana temporaria. In combination with Raman microspectroscopy, allowing noninvasive live-cell measurements, we employed time-of-flight secondary ion mass spectrometry (TOF-SIMS) to follow the underlying changes in chemical composition of myelin membranes triggered by the purinergic agents. The simultaneous increase in lipid ordering degree, decrease in membrane fluidity and the degree of fatty acid unsaturation were induced by both ATP and adenosine. Mass spectrometry measurements revealed that ATP administration also led to the marked elevation of membrane cholesterol and decrease of phosphotidylcholine amounts. Vesicular lipid transport pathways are considered as possible mechanisms of compositional and structural changes of myelin. PMID- 26544551 TI - A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Galpha and Gbetagamma. AB - G protein-gated K+ channels (GIRK; Kir3), activated by Gbetagamma subunits derived from Gi/o proteins, regulate heartbeat and neuronal excitability and plasticity. Both neurotransmitter-evoked (Ievoked) and neurotransmitter independent basal (Ibasal) GIRK activities are physiologically important, but mechanisms of Ibasal and its relation to Ievoked are unclear. We have previously shown for heterologously expressed neuronal GIRK1/2, and now show for native GIRK in hippocampal neurons, that Ibasal and Ievoked are interrelated: the extent of activation by neurotransmitter (activation index, Ra) is inversely related to Ibasal. To unveil the underlying mechanisms, we have developed a quantitative model of GIRK1/2 function. We characterized single-channel and macroscopic GIRK1/2 currents, and surface densities of GIRK1/2 and Gbetagamma expressed in Xenopus oocytes. Based on experimental results, we constructed a mathematical model of GIRK1/2 activity under steady-state conditions before and after activation by neurotransmitter. Our model accurately recapitulates Ibasal and Ievoked in Xenopus oocytes, HEK293 cells and hippocampal neurons; correctly predicts the dose-dependent activation of GIRK1/2 by coexpressed Gbetagamma and fully accounts for the inverse Ibasal-Ra correlation. Modeling indicates that, under all conditions and at different channel expression levels, between 3 and 4 Gbetagamma dimers are available for each GIRK1/2 channel. In contrast, available Galphai/o decreases from ~2 to less than one Galpha per channel as GIRK1/2's density increases. The persistent Gbetagamma/channel (but not Galpha/channel) ratio support a strong association of GIRK1/2 with Gbetagamma, consistent with recruitment to the cell surface of Gbetagamma, but not Galpha, by GIRK1/2. Our analysis suggests a maximal stoichiometry of 4 Gbetagamma but only 2 Galphai/o per one GIRK1/2 channel. The unique, unequal association of GIRK1/2 with G protein subunits, and the cooperative nature of GIRK gating by Gbetagamma, underlie the complex pattern of basal and agonist-evoked activities and allow GIRK1/2 to act as a sensitive bidirectional detector of both Gbetagamma and Galpha. PMID- 26544553 TI - The Effect of Axial Length on the Thickness of Intraretinal Layers of the Macula. AB - PURPOSE: The aim of this study was to evaluate the effect of axial length (AL) on the thickness of intraretinal layers in the macula using optical coherence tomography (OCT) image analysis. METHODS: Fifty three randomly selected eyes of 53 healthy subjects were recruited for this study. The median age of the participants was 29 years (range: 6 to 67 years). AL was measured for each eye using a Lenstar LS 900 device. OCT imaging of the macula was also performed by Stratus OCT. OCTRIMA software was used to process the raw OCT scans and to determine the weighted mean thickness of 6 intraretinal layers and the total retina. Partial correlation test was performed to assess the correlation between the AL and the thickness values. RESULTS: Total retinal thickness showed moderate negative correlation with AL (r = -0.378, p = 0.0007), while no correlation was observed between the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCC), retinal pigment epithelium (RPE) and AL. Moderate negative correlation was observed also between the thickness of the ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and AL which were more pronounced in the peripheral ring (r = -0.402, p = 0.004; r = -0.429, p = 0.002; r = -0.360, p = 0.01; r = -0.448, p = 0.001). CONCLUSIONS: Our results have shown that the thickness of the nuclear layers and the total retina is correlated with AL. The reason underlying this could be the lateral stretching capability of these layers; however, further research is warranted to prove this theory. Our results suggest that the effect of AL on retinal layers should be taken into account in future studies. PMID- 26544554 TI - Surveillance of Tuberculosis in Taipei: The Influence of Nontuberculous Mycobacteria. AB - BACKGROUND: Notification of tuberculosis (TB) but not nontuberculous mycobacteria (NTM) is mandatory in Taiwan. Partly due to the strict regulation on TB notification, several patients infected with NTM were notified as TB cases. Notification of patients infected with NTM as TB cases can trigger public health actions and impose additional burdens on the public health system. We conducted a study to assess the influence of NTM infection on surveillance of TB in Taipei. METHODOLOGY/PRINCIPAL FINDINGS: The study population included all individuals with a positive culture for Mycobacterium who were citizens of Taipei City and notified as TB cases in the calendar years 2007-2010. Of the 4216 notified culture-positive tuberculosis (TB) cases, 894 (21.2%) were infected with NTM. The average annual reported case rate of infection with NTM was 8.6 (95% confidence interval 7.7-9.4) per 100,000 people. The reported case rate of NTM increased with age in both males and females. The proportion of reported TB cases infected with NTM was significantly higher in females than in males (27.6% vs 17.8%, adjusted OR (adjOR) 1.93, 95% confidence interval (CI) 1.63-2.28); in smear positive than in smear-negative (23.1% vs 19.2%, adjOR 1.26, 95% CI 1.08-1.47); and in previously treated cases than in new cases (35.7% vs 19.1%, adjOR 2.30, 95% CI 1.88-2.82). The most frequent species was M. avium complex (32.4%), followed by M. chelonae complex (17.6%), M. fortuitum complex (17.0%) and M. kansasii (9.8%). Of the 890 notified NTM cases assessed, 703 (79.0%) were treated with anti-TB drugs, and 730 (82.0%) were de-notified. CONCLUSIONS/SIGNIFICANCE: The influence of NTM on surveillance of TB in Taipei was substantial. Health authorities should take action to ensure that nucleic acid amplification tests are performed in all smear-positive cases in a timely manner to reduce the misdiagnosis of patients infected with NTM as TB cases. PMID- 26544555 TI - Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift. AB - Heterotopic ossification (HO) is the growth of extra-skeletal bone which occurs following trauma, burns, and in patients with genetic bone morphogenetic protein (BMP) receptor mutations. The clinical and laboratory evaluation of HO is dependent on radiographic imaging to identify and characterize these lesions. Here we show that despite its inadequacies, plain film radiography and single modality microCT continue to serve as a primary method of HO imaging in nearly 30% of published in vivo literature. Furthermore, we demonstrate that detailed microCT analysis is superior to plain film and single modality microCT radiography specifically in the evaluation of HO formed through three representative models due to its ability to 1) define structural relationships between growing extra-skeletal bone and normal, anatomic bone, 2) provide accurate quantification and growth rate based on volume of the space-occupying lesion, thereby facilitating assessments of therapeutic intervention, 3) identify HO at earlier times allowing for evaluation of early intervention, and 4) characterization of metrics of bone physiology including porosity, tissue mineral density, and cortical and trabecular volume. Examination of our trauma model using microCT demonstrated two separate areas of HO based on anatomic location and relationship with surrounding, normal bone structures. Additionally, microCT allows HO growth rate to be evaluated to characterize HO progression. Taken together, these data demonstrate the need for a paradigm shift in the evaluation of HO towards microCT as a standard tool for imaging. PMID- 26544556 TI - Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow. AB - OBJECTIVES: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow. METHODS: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints. CONCLUSIONS: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings. PMID- 26544557 TI - Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover. AB - Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution, a mutant yeast strain was engineered to translate a codon ambiguously (mistranslation). It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. Genomic analysis demonstrated that adaptation was primarily mediated by large-scale chromosomal duplication and deletion events, suggesting that errors during protein synthesis promote the evolution of genome architecture. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome-mediated protein degradation and protein synthesis. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. However, there was a strong evolutionary trade-off between adaptation to mistranslation and survival upon starvation: the evolved lines showed fitness defects and impaired capacity to degrade mature ribosomes upon nutrient limitation. Moreover, as a response to an enhanced energy demand of accelerated protein turnover, the evolved lines exhibited increased glucose uptake by selective duplication of hexose transporter genes. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. Our work also indicates that translational fidelity and the ubiquitin-proteasome system are functionally linked to each other and may, therefore, co-evolve in nature. PMID- 26544558 TI - Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis. AB - BACKGROUND: Myelodysplastic syndromes (MDS) are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML). Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT) and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells. METHODS: SKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI) values. Western blot was used to analysis phosphorylation of Akt and nuclear NF kappaB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151. RESULTS: Simultaneous exposure to HHT and Bortezomib (10.4:1) resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05). Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05). HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01). The mechanisms of the synergy involved Akt and NF-kappaB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01). CONCLUSIONS: HHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-kappaB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR 3151 abundance is implicated in SKM-1 cell viability, cell proliferation and p53 protein expression. PMID- 26544559 TI - Visual Outcomes and Optical Quality After Femtosecond Laser Small Incision Lenticule Extraction: An 18-Month Prospective Study. AB - PURPOSE: To investigate the long-term visual outcomes and optical quality after femtosecond laser small incision lenticule extraction (SMILE) for moderate to high myopia correction. METHODS: Fifty-four patients (37 women, 17 men) who underwent SMILE were enrolled in this prospective clinical study. Patient ages ranged from 18 to 40 years, with a mean spherical equivalent of -6.50 +/- 1.64 diopters. Data including refractive parameters, retinal image quality, intraocular scattering, and aberrations were collected at 6 and 18 months after surgery. Patient satisfaction was also evaluated. RESULTS: At 18 months after surgery, both the mean safety index and the efficacy index were 1.23 +/- 0.23 (range: 0.80 to 1.50); there was no significant difference with indices measured at 6 months (P > .05). No patient lost two or more lines of corrected distance visual acuity. Total higher-order aberrations (HOAs) and coma significantly increased after SMILE (P < .05), whereas total spherical aberrations and trefoil changed only slightly. The mean modulation transfer function cutoff frequency was 36.66 +/- 8.54 cycles per degree (cpd) before surgery and 37.81 +/- 6.89 cpd at 18 months postoperatively; the mean objective scatter index was 0.62 +/- 0.33 before surgery and 0.71 +/- 0.38 at 18 months postoperatively. No significant difference was found between the three time points (P > .05). Mean patient satisfaction was 9.31 +/- 0.64 (with a maximum score of 10). CONCLUSIONS: SMILE showed good safety, efficacy, and stability in correcting moderate to high myopia, and patients were highly satisfied. HOAs increased after SMILE, mainly due to the increase of coma, whereas retinal image quality and intraocular scattering barely changed. PMID- 26544560 TI - Lenticule Quality After Continuous Curvilinear Lenticulerrhexis in SMILE Evaluated With Scanning Electron Microscopy. AB - PURPOSE: To evaluate the surface characteristics of lenticules extracted by continuous curvilinear lenticulerrhexis (CCL) in small incision lenticule extraction. METHODS: Twelve eyes treated with small incision lenticule extraction were included in the study and divided into two groups: the CCL and traditional groups. The extracted lenticules were examined with scanning electron microscopy. Both the anterior and the posterior surfaces of the lenticules were accessed. A scoring system was used to evaluate surface characteristics of the lenticules with a full mark of 16. RESULTS: All of the lenticules in the CCL group exhibited smoothness and regularity on both sides and received scores of 14 or 15. The average score of anterior surfaces was 14.83 +/- 0.41 for the CCL group and 14.00 +/- 2.45 for the traditional group. The average score for the posterior surfaces was 14.50 +/- 0.55 for the CCL group and 14.83 +/- 0.41 for the traditional group. CONCLUSIONS: The surfaces of lenticules extracted by the CCL technique in small incision lenticule extraction are of good quality. PMID- 26544531 TI - EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine Disrupting Chemicals. AB - The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions. PMID- 26544562 TI - Straylight Measurements in Two Different Apodized Diffractive Multifocal Intraocular Lenses. AB - PURPOSE: To evaluate differences in straylight between eyes implanted with a hydrophilic multifocal IOL (Seelens MF; Hanita Lenses, Hanita, Israel) and a hydrophobic multifocal IOL (SN6AD1; Alcon Laboratories, Inc., Fort Worth, TX). METHODS: In a prospective cohort study, routinely obtained straylight measurements (C-Quant; Oculus Optikgerate, Wetzlar, Germany) 3 months after standard phacoemulsification for either cataract or refractive lens procedures were compared. Patients were implanted with either the SeeLens MF IOL or the SN6AD1 IOL. Postoperative straylight values, visual acuity, and refractive outcomes were compared. RESULTS: The SeeLens MF IOL was implanted in 84 eyes and the SN6AD1 IOL in 79 eyes. The difference in straylight was 0.08 (P = .01), with the SeeLens MF IOL having less straylight. Postoperative CDVA was logMAR -0.03 +/ 0.06 in the SeeLens MF group, and logMAR -0.02 +/- 0.08 in the SN6AD1 group. Mean postoperative refraction was +0.01 +/- 0.43 and +0.06 +/- 0.35 D, respectively. CONCLUSIONS: The Seelens MF IOL showed a stray-light of log(s) 0.08 lower than the SN6AD1 IOL. In terms of spherical equivalent and visual acuity the lenses performed equally. More study will aid in understanding the causes and clinical impact of this difference. PMID- 26544561 TI - Detection of Keratoconus in Clinically and Algorithmically Topographically Normal Fellow Eyes Using Epithelial Thickness Analysis. AB - PURPOSE: To assess the effectiveness of a keratoconus-detection algorithm derived from Artemis very high-frequency (VHF) digital ultrasound (ArcScan Inc., Morrison, CO) epithelial thickness maps in the fellow eye from a series of patients with unilateral keratoconus. METHODS: The study included 10 patients with moderate to advanced keratoconus in one eye but a clinically and algorithmically topographically normal fellow eye. VHF digital ultrasound epithelial thickness data were acquired and a previously developed classification model was applied for identification of keratoconus to the clinically normal fellow eyes. Pentacam (Oculus Optikgerate, Wetzlar, Germany) Belin-Ambrosio Enhanced Ectasia Display "D" score (BAD-D) data (5 of 10 eyes), and Orbscan (Bausch & Lomb, Rochester, NY) SCORE data (9 of 10 eyes) were also evaluated. RESULTS: Five of the 10 fellow eyes were classified as keratoconic by the VHF digital ultrasound epithelium model. Five of 9 fellow eyes were classified as keratoconic by the SCORE model. For the 5 fellow eyes with Pentacam and VHF digital ultrasound data, one was classified as keratoconic by the VHF digital ultrasound model, one (different) eye by a combined VHF digital ultrasound and Pentacam model, and none by BAD-D alone. CONCLUSIONS: Under the assumption that keratoconus is a bilateral but asymmetric disease, half of the 'normal' fellow eyes could be found to have keratoconus using epithelial thickness maps. The Orbscan SCORE or the combination of topographic BAD-D criteria with epithelial maps did not perform better. PMID- 26544563 TI - Comparison of Forward Light Scatter Changes Between SMILE, Femtosecond Laser assisted LASIK, and Epipolis LASIK: Results of a 1-Year Prospective Study. AB - PURPOSE: To investigate the characteristics of forward light scatter changes after small incision lenticule extraction (SMILE) and to compare these changes with those after femtosecond laser-assisted LASIK (femto-LASIK) and epipolis LASIK (epi-LASIK). METHODS: A total of 303 eyes (SMILE group = 118 eyes, femto LASIK group = 90 eyes, epi-LASIK group = 95) of 157 patients were included in this study. Forward straylight was measured preoperatively and 1 month, 6 months, and 1 year postoperatively using a C-Quant straylight meter (Oculus Optikgerate, Wetzlar, Germany). RESULTS: A significant increase in straylight was found in the femto-LASIK group only at 1 month after the procedure (P = .002), whereas significant increases were found in the epi-LASIK group at 1 month, 6 months, and 1 year after the procedure (P < .001). There were no significant increases in the straylight values after SMILE (P = .310) compared with the preoperative values, although the straylight values were slightly increased at 1 month. Significant differences in the postoperative-preoperative straylight value (Deltalog[s]) changes were found between the SMILE, femto-LASIK, and epi-LASIK groups over the follow-up period (P < .001 for all). The correlations between the ablation depth/central corneal thickness ratios and the straylight values were statistically significant in the femto-LASIK and epi-LASIK groups, whereas no significant correlation between the lenticule thickness/central corneal thickness ratios and the stray-light values was found in the SMILE group. CONCLUSIONS: Forward straylight was slightly increased in the early stage after the femto LASIK procedure and was significantly increased throughout the follow-up period after epi-LASIK surgery. The SMILE procedure appeared to have a smaller effect on forward light scatter within the 1-year follow-up period. PMID- 26544564 TI - Comparison of Three Epithelial Removal Techniques in PRK: Mechanical, Alcohol assisted, and Transepithelial Laser. AB - PURPOSE: To compare the visual and refractive results obtained after photorefractive keratectomy (PRK) in patients who underwent one of three different epithelial removal techniques. METHODS: The authors reviewed the medical files of consecutive eyes with myopia and myopic astigmatism that were treated during a 10-year period by mechanical PRK, alcohol-assisted PRK, or transepithelial PRK (in the phototherapeutic keratectomy mode), and observed for more than 1 year. RESULTS: A total of 3,417 patients (3,417 eyes) were included in this study. At 3 and 6 months postoperatively, the outcome of alcohol-assisted PRK was superior both in efficacy (P < .01) and safety (P < .001) to those of both mechanical PRK and transepithelial PRK, which were similar. At more than 1 year postoperatively, the mean efficacy index was still high for alcohol-assisted PRK, but low for the transepithelial PRK, corresponding to a mean uncorrected visual acuity of more than one Snellen line lower than those of the other two techniques (P < .0001). All three techniques showed a regression toward myopia more than 1 year postoperatively, with significant undercorrection obtained in eyes treated with transepithelial PRK (P < .0001). CONCLUSIONS: Significant differences were detected in both the visual outcomes and the refractive results of the three epithelial removal techniques. The long-term outcomes were best for alcohol-assisted PRK. PMID- 26544565 TI - Novel Placido-derived Topography-guided Excimer Corneal Normalization With Cyclorotation Adjustment: Enhanced Athens Protocol for Keratoconus. AB - PURPOSE: To comparatively investigate the efficacy of the enhanced Athens Protocol procedure guided by novel Placido-derived topography with cyclorotation compensation (the cyclorotation adjusted group) to similar cases guided by Scheimpflug-derived tomography without cyclorotation compensation (the non cyclorotation adjusted group). METHODS: Two groups were evaluated: the cyclorotation adjusted group (n = 110 eyes) and the non-cyclorotation adjusted group (n = 110 eyes). Analysis was based on digital processing of Scheimpflug imaging derived curvature difference maps preoperatively and 3 months postoperatively. The vector (r, theta) corresponding to the steepest corneal point (cone) on the preoperative surgical planning map (rp, thetap) and on the curvature difference map (rd, thetad) were computed. The differences between the peak topographic angular data (Deltatheta = |thetap - thetad|) and weighted angular difference (WDeltatheta = Deltatheta * Deltar) were calculated. RESULTS: For the cyclorotation adjusted group, Deltatheta was 7.18 degrees +/- 7.53 degrees (range: 0 degrees to 34) and WDeltatheta was 3.43 +/- 4.76 mm (range: 0.00 to 21.41 mm). For the non-cyclorotation adjusted group, Deltatheta was 14.50 degrees +/- 12.65 degrees (range: 0 degrees to 49 degrees ) and WDeltatheta was 10.23 +/- 15.15 mm (range: 0.00 to 80.56 mm). The cyclorotation adjusted group appeared superior to the non-cyclorotation adjusted group, in both the smaller average angular difference between attempted to achieved irregular curvature normalization and in weighted angular difference, by a statistically significant margin (Deltatheta: P = .0058; WDeltatheta: P = .015). CONCLUSIONS: This study suggests that employment of the novel Placido-derived topographic data of highly irregular corneas, such as in keratoconus, treated with topography guided profile with cyclorotation compensation leads to markedly improved cornea normalization. PMID- 26544566 TI - Femtosecond Laser-assisted Endokeratophakia Using Allogeneic Corneal Lenticule in a Rabbit Model. AB - PURPOSE: To investigate the feasibility of allogeneic corneal lenticule implantation using the femtosecond laser as a method for cornea remodeling. METHODS: Small incision lenticule extraction was performed on the right eyes of 15 New Zealand white rabbits. Corneal intrastromal pockets were created with a femtosecond laser on the left eyes. Allogeneic corneal lenticule implantation was performed on the left eye immediately after the lenticule was extracted from the right eye. All animals had preoperative and postoperative slit-lamp photography, ultrasonic pachymetry, corneal endothelial cell count, anterior segment optical coherence tomography, in vivo confocal microscopy, and retinoscopy refraction during the observation period of 8 weeks. The rabbits were killed 8 weeks after surgery. Corneal wound healing response was analyzed by transmission electron microscopy, hematoxylin-eosin staining, TUNEL assay, and immunofluorescent staining. RESULTS: Mild corneal edema and decreased clarity were noted the first few days after implantation, improving to normal 8 weeks after surgery. The corneal thickness and retinoscopy refraction were stable during the observation period. Viable keratocytes could be detected within the lenticule lamellae by ultrastructural analysis 8 weeks after surgery. The anterior and posterior border of the lenticule showed acellular layers with highly irregular collagen arrangement on transmission electron microscope images. Proliferating Ki-67 positive cells were present only in the epithelium layer. CONCLUSION: Femtosecond laser-assisted endokeratophakia using allogeneic corneal lenticule may be feasible for reshaping cornea, providing a new possibility in refractive surgery and keratoconus treatment. PMID- 26544567 TI - Prenatal Exposure to Cadmium, Placental Permeability and Birth Outcomes in Coastal Populations of South Africa. AB - BACKGROUND: The impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa. METHODS: Cadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts. RESULTS: The average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 MUg/L (n = 641; 95% CI, 0.23-0.27). The cord blood Cd level was 0.27 MUg/L (n = 317; 95% CI, 0.26-0.29) and urine (creatinine corrected) Cd level was 0.27 MUg/L (n = 318; 95% CI, 0.24-0.29). The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (beta = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (beta = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts. DISCUSSION: Significant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd. PMID- 26544569 TI - Application of Penalized Regression Techniques in Modelling Insulin Sensitivity by Correlated Metabolic Parameters. AB - This paper aims to introduce penalized estimation techniques in clinical investigations of diabetes, as well as to assess their possible advantages and limitations. Data from a previous study was used to carry out the simulations to assess: a) which procedure results in the lowest prediction error of the final model in the setting of a large number of predictor variables with high multicollinearity (of importance if insulin sensitivity should be predicted) and b) which procedure achieves the most accurate estimate of regression coefficients in the setting of fewer predictors with small unidirectional effects and moderate correlation between explanatory variables (of importance if the specific relation between an independent variable and insulin sensitivity should be examined). Moreover a special focus is on the correct direction of estimated parameter effects, a non-negligible source of error and misinterpretation of study results. The simulations were performed for varying sample size to evaluate the performance of LASSO, Ridge as well as different algorithms for Elastic Net. These methods were also compared with automatic variable selection procedures (i.e. optimizing AIC or BIC).We were not able to identify one method achieving superior performance in all situations. However, the improved accuracy of estimated effects underlines the importance of using penalized regression techniques in our example (e.g. if a researcher aims to compare relations of several correlated parameters with insulin sensitivity). However, the decision which procedure should be used depends on the specific context of a study (accuracy versus complexity) and moreover should involve clinical prior knowledge. PMID- 26544568 TI - Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients. AB - Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC. PMID- 26544570 TI - Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. METHODS: We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. RESULTS: During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. CONCLUSION: We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted. PMID- 26544571 TI - DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation. AB - Proper development of the immune system is an intricate process dependent on many factors, including an intact DNA damage response. The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofactor, ATMIN (also known as ASCIZ) in T cells is much less clear, and whether ATMIN and NBS1 function in synergy in T cells is unknown. Here, we investigate the roles of ATMIN and NBS1, either alone or in combination, using murine models. We show loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCRalpha recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment. Intriguingly, the disease causing T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted in severe intestinal inflammation, colitis and premature death. Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1. PMID- 26544572 TI - Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures. AB - BACKGROUND: Papillomaviruses and polyomaviruses are small ds-DNA viruses infecting a wide-range of vertebrate hosts. Evidence supporting co-evolution of the virus with the host does not fully explain the evolutionary path of papillomaviruses and polyomaviruses. Studies analyzing CpG dinucleotide frequencies in virus genomes have provided interesting insights on virus evolution. CpG dinucleotide depletion has not been extensively studied among papillomaviruses and polyomaviruses. We sought to analyze the relative abundance of dinucleotides and the relative roles of evolutionary pressures in papillomaviruses and polyomaviruses. METHODS: We studied 127 full-length sequences from papillomaviruses and 56 full-length sequences from polyomaviruses. We analyzed the relative abundance of dinucleotides, effective codon number (ENC), differences in synonymous codon usage. We examined the association, if any, between the extent of CpG dinucleotide depletion and the evolutionary lineage of the infected host. We also investigated the contribution of mutational pressure and translational selection to the evolution of papillomaviruses and polyomaviruses. RESULTS: All papillomaviruses and polyomaviruses are CpG depleted. Interestingly, the evolutionary lineage of the infected host determines the extent of CpG depletion among papillomaviruses and polyomaviruses. CpG dinucleotide depletion was more pronounced among papillomaviruses and polyomaviruses infecting human and other mammals as compared to those infecting birds. Our findings demonstrate that CpG depletion among papillomaviruses is linked to mutational pressure; while CpG depletion among polyomaviruses is linked to translational selection. We also present evidence that suggests methylation of CpG dinucleotides may explain, at least in part, the depletion of CpG dinucleotides among papillomaviruses but not polyomaviruses. CONCLUSIONS: The extent of CpG depletion among papillomaviruses and polyomaviruses is linked to the evolutionary lineage of the infected host. Our results highlight the existence of divergent evolutionary pressures leading to CpG dinucleotide depletion among small ds-DNA viruses infecting vertebrate hosts. PMID- 26544573 TI - A ligand-entry surface of the nuclear receptor superfamily consists of the helix H3 of the ligand-binding domain. AB - We successfully simulated receptor-ligand complex holo-form formation using the human retinoid X receptor-alpha ligand-binding domain (LBD) and its natural ligand, 9-cis retinoic acid. The success of this simulation was strongly dependent on the findings for an initial structure between the apo-LBD and the ligand as well as the discovery of the driving forces underlying the ligand trapping and subsequent ligand-induction processes. Here, we would like to propose the "helix H3 three-point initial-binding hypothesis," which was instrumental in simulating the nuclear receptor (NR) superfamily. Using this hypothesis, we also succeeded in simulating holo-form formation of the human retinoic acid receptor-gamma LBD and its natural ligand, all-trans retinoic acid. It is hoped that this hypothesis will facilitate novel understanding of both the ligand-trapping mechanism and the simultaneous C-terminal folding process in NR LBDs, as well as provide a new approach to drug design using a structure-based perspective. PMID- 26544574 TI - Hit me with your best shot: dolutegravir - a space in the next WHO guidelines? PMID- 26544575 TI - No evidence of posttreatment control after early initiation of antiretroviral therapy. AB - As part of a retrospective analysis of 616 individuals followed from incident HIV infection for up to 18 years as part of the San Diego Primary Infection Cohort, we found 16 individuals who started antiretroviral therapy (ART) within the first 4 months of infection and subsequently interrupted ART after being virologically suppressed for a median of 1.75 years. No individual maintained sustained virologic control after interruption of ART, even when treatment was started during the earliest stages of HIV infection. Median time to HIV-RNA rebound after ART interruption was 0.9 months (range: 0.2-6.4 months). PMID- 26544578 TI - Cognitive functioning, wellbeing and brain correlates in HIV-1 infected patients on long-term combination antiretroviral therapy. AB - OBJECTIVE: The objective of the current study is to integrate results from extensive neuropsychological assessment, subjective wellbeing reports and structural neuroimaging findings in successfully treated HIV-infected patients in comparison with a HIV-negative control group. DESIGN: A cross-sectional study. METHODS: Neuropsychological functioning and self-reported wellbeing were assessed in a group of 102 virologically suppressed HIV-infected patients on combination antiretroviral therapy (cART) and 56 controls. Both groups underwent magnetic resonance (MR) examinations and grey matter, white matter and subcortical volumes were determined. Brain parenchymal fraction (BPF) was calculated as an estimated measure of global brain atrophy. RESULTS: HIV-infected patients showed worse information processing speed (P = 0.01) and motor function (P = 0.03) than controls. Also, higher levels of anxiety and depressive symptoms, somatic and cognitive complaints, sleep problems and health distress were found, as well as lower levels of general health perceptions, social functioning and energy (P < 0.05). No differences in wellbeing reports were found between patients on regimens containing either efavirenz or nevirapine and patients on cART without these drugs (P > 0.05). Patients had a smaller BPF (P = 0.04) and thalamus (P = 0.05) than controls. A lower BPF was related to worse motor function and information processing speed in the patients. A smaller thalamus volume was related to lower motor function in the patient group and lower speed of information processing in the controls. CONCLUSION: No profound deficits were found in the current study. The present results demonstrate that HIV has a minor impact on brain, cognition and wellbeing among HIV-infected patients who are otherwise healthy and maintained on a good control of cART. PMID- 26544576 TI - Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients. AB - OBJECTIVES: We studied the link between T-cell activation, differentiation and senescence phenotypes and non-AIDS-related comorbidities in HIV-suppressed patients. DESIGN: Patients included in the ANRS CO3 Aquitaine Cohort were consecutively enrolled in this cross-sectional study between October 2011 and May 2013 called Chronic Immune Activation and Senescence (CIADIS) study. METHODS: We summarized immune markers [CD4 and CD8 activation (DR), differentiation (naive and terminally differentiated memory T cells), and senescence (CD57CD28)] in a weighted immune score by principal component analysis called CIADIS. Previously described Veterans Aging Cohort Study (VACS) index and immune risk profile (IRP) scores were calculated. We used adjusted logistic regression to assess the association between the CIADIS score and the presence of at least three non-AIDS defining comorbidities. RESULTS: Of 876 patients with an undetectable viral load, 73.4% were men and median age was 50.5 years [interquartile range (IQR) 44.7-56.7 years]. Median CD4 T-cell count was 579/MUl (IQR 429-759 cells/MUl), and median duration of HIV viral suppression was 5.3 years (IQR 2.3-8.7). The weighted CIADIS score was associated with at least three comorbidities (odds ratio 1.3 for 1 SD more, 95% confidence interval 1.0, 1.6) independently of age, sex, AIDS stage, and the Veterans Aging Cohort Study score. The CIADIS and the immune risk profile scores were significantly associated with at least three comorbidities in adjusted models restricted to patients younger than 60 years. None of the tested scores were associated with at least three comorbidities in patients older than 60 years. CONCLUSIONS: The weighted CIADIS score based on activation, senescence, and differentiation markers might help physicians identifying patients at a higher risk for non-AIDS-related comorbidities. PMID- 26544579 TI - Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers. AB - OBJECTIVE: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans. DESIGN AND METHODS: Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600 mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200 mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4 h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation. RESULTS: Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1 ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells. CONCLUSIONS: An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission. PMID- 26544580 TI - Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AB - Maraviroc (MVC) is not approved for HIV-1-infected paediatric patients. This is the first assessment of the use of MVC-based salvage therapy in vertically HIV-1 infected paediatric patients in clinical settings. The results suggest that MVC based salvage therapy is useful in children and adolescents with extensive resistance profile leading to maintained virological suppression in up to 88% of the patients with CCR5-tropic virus. The likelihood of treatment success might increase when MVC is combined with other active drugs. PMID- 26544577 TI - Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery. AB - BACKGROUND: Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4 T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals with incomplete CD4 T cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks. DESIGN: A5256 was a single-arm trial in which individuals on suppressive ART with incomplete CD4 T cell recovery added maraviroc for 24 weeks. METHODS: We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-long terminal repeat (2-LTR) circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4 and CD8 T-cell immune activation (%CD38HLA-DR) and apoptosis (%caspase3/Bcl-2). RESULTS: No effect of maraviroc was found on the probability of detectable plasma viremia (>=1 copy/ml; n = 31, exact McNemar P = 1.0) or detectable 2-LTR circles (n = 28, P = 0.25) or on total HIV-1 DNA (n = 28, 90% confidence interval -0.1, +0.3 log10 copies/10 CD4 T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38HLA-DR CD4 T-cells (Spearman = -0.52, P = 0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38HLA DR CD4 T-cells during maraviroc intensification (Spearman = 0.44, P = 0.018). CONCLUSION: In individuals on suppressive ART with incomplete CD4 T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4 T-cell immune activation especially in individuals with low preintensification levels of HIV-1 DNA. PMID- 26544581 TI - Disclosure of pharmacokinetic drug results to understand nonadherence. AB - OBJECTIVES: In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. METHODS: We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (>=75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. RESULTS: We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. CONCLUSION: Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials. PMID- 26544582 TI - Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality. AB - OBJECTIVE: To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN: Prospective observational cohort study. METHODS: Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS: Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION: Self report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention. PMID- 26544583 TI - Obesity is associated with greater inflammation and monocyte activation among HIV infected adults receiving antiretroviral therapy. AB - OBJECTIVES: Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been associated with excess HIV-related cardiovascular disease and mortality. METHODS: We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers [soluble CD163 (sCD163), sCD14], and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels. RESULTS: Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4 cell count was 475 (308-697) cells/MUl, and 21% were obese (BMI >= 30 kg/m). In univariable models, obesity, smoking, and lower CD4 cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 [odds ratio (OR) 1.96; P = 0.02], highly sensitive C-reactive protein (OR 2.79; P < 0.001) and sCD163 (OR 1.94; P = 0.02), and elevated frequency of CD14CD16 (OR 1.77; P = 0.03) and CD14dimCD16 (OR 1.97; P = 0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation. CONCLUSION: Obesity was prevalent and independently associated with greater monocyte activation and systemic inflammation. Research is needed to determine how adipose tissue excess is functionally related to persistent immunologic abnormalities among HIV-infected persons with viral suppression. PMID- 26544584 TI - Tropism distribution among antiretroviral-naive HIV-2-infected patients. AB - The aim of this study was to describe HIV-2 R5/X4-tropism distribution in antiretroviral-naive HIV-2-infected patients. Population sequencing of the gp105 region was performed on peripheral blood mononuclear cells issued from 151 antiretroviral-naive patients. Tropism was successfully determined in 46 of 151 samples (30%) with six of 46 (13%) X4-tropic viruses. X4-tropism was associated with lower CD4 cell count (337 vs. 551/mm; P = 0.032) but not with plasma viral load. Thus, X4-tropism prevalence in HIV-2 antiretroviral-naive patients is similar to that observed in HIV-1. PMID- 26544585 TI - Clinical relevance of cross-reactivity between darunavir and trimethoprim sulfamethoxazole in HIV-infected patients. PMID- 26544586 TI - Incidence of darunavir hypersensitivity in different clinical cohorts. PMID- 26544587 TI - Disseminated mucormycosis-induced perforated intestine in a late presenting AIDS patient with steroid-dependent secondary hemophagocytic lymphohistiocytosis. PMID- 26544588 TI - Effective but expensive hepatitis C treatment for patients with HIV. PMID- 26544589 TI - Organ donations between HIV-positive individuals. PMID- 26544590 TI - Replicative fitness of transmitted HIV-1 drives disease progression. PMID- 26544591 TI - The best way to proceed when an HIV-discordant couple desires a child. PMID- 26544592 TI - Targeting Tuberculosis and HIV Infection-Specific Regulatory T Cells with MEK/ERK Signaling Pathway Inhibitors. AB - Human regulatory T cells (Tregs) are essential in maintaining immunological tolerance and suppress effector T cells. Tregs are commonly up-regulated in chronic infectious diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection and thereby hamper disease-specific immune responses and eradication of pathogens. The MEK/ERK signaling pathway is involved in regulation of the FoxP3 transcription factor, which directs a lineage-specific transcriptional program to define Tregs and control their suppressive function. Here, we aimed to target activation of disease-specific Tregs by inhibition of the MEK/ERK signaling pathway based on the hypothesis that this would improve anti-HIV and anti-TB immunity. Stimulation of T cells from untreated TB (n = 12) and HIV (n = 8) patients with disease-specific antigens in vitro in the presence of the MEK inhibitor (MEKI) trametinib (GSK1120212) resulted in significant down regulation of both FoxP3 levels (MFI) and fractions of resting (CD45RA+FoxP3+) and activated (CD45RA-FoxP3++) Tregs. MEKI also reduced the levels of specific T effector cells expressing the pro-inflammatory cytokines (IFN-gamma, TNF-alpha and IL-2) in both HIV and TB patients. In conclusion, MEKIs modulate disease antigen-specific Treg activation and may have potential application in new treatment strategies in chronic infectious diseases where reduction of Treg activity would be favorable. Whether MEKIs can be used in current HIV or TB therapy regimens needs to be further investigated. PMID- 26544593 TI - Reduced D2/D3 Receptor Binding of Extrastriatal and Striatal Regions in Temporal Lobe Epilepsy. AB - OBJECTIVE: Dopamine is an endogenous neuromodulator in cortical circuits and the basal ganglia. In animal models of temporal lobe epilepsy (TLE), seizure threshold is modulated to some extent by dopamine, with D1-receptors having a pro and D2-receptors an anticonvulsant effect. We aimed to extend our previously reported results on decreased D2/D3 receptor binding in the lateral epileptogenic temporal lobe and to correlate them with demographic and seizure variables to gain a more comprehensive understanding of the underlying involvement of the dopaminergic system in the epileptogenesis of TLE. METHODS: To quantify D2/D3 receptor binding, we studied 21 patients with TLE and hippocampal sclerosis (13 left- and eight right-sided) and 18 controls using PET with the high-affinity dopamine D2/D3-receptor ligand 18F-Fallypride to image striatal and extrastriatal binding. TLE was defined by interictal and ictal video-EEG, MRI and 18F Fluorodeoxyglucose PET. Voxel-based statistical and regions-of-interest analyses were performed. RESULTS: 18F-Fallypride binding potential was significantly reduced in the affected temporal lobe and bilateral putamen. A positive correlation between age at onset of epilepsy and [18F]FP BPnd (binding potential non-displaceable) in temporal regions on the epileptogenic side was found, as well as a negative correlation between epilepsy duration and [18F]FP BPnd in the temporal pole on the epileptogenic side and a positive correlation between the estimated number of lifetime GTCS and [18F]FP BPnd in the hippocampus on the epileptogenic side. SIGNIFICANCE: The areas of reduced D2/D3 receptor availability correspond to "the irritative zone" surrounding the epileptogenic area. Moreover, reduced D2/D3 receptor availability was detectable in the basal ganglia, which are suspected to be involved in a control circuit for epileptic seizures. The correlational analysis additionally suggests that increased epilepsy duration leads to increasing impairment of the dopaminergic system. PMID- 26544595 TI - A systematic review of clinical outcomes for patients diagnosed with skin cancer spinal metastases. AB - OBJECT Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype. METHODS The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool. RESULTS Sixty five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0% 88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0.2%-100.0%), and the rate of known spine metastasis recurrence despite treatment for all skin malignancies was 2.8% (n = 17/608, range 0.0%-33.3%). Age greater than 65 years, sacral spinal involvement, presence of a neurological deficit, and nonambulatory status were associated with decreased survival in patients diagnosed with a primary skin cancer spinal metastasis. All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSIONS Patients diagnosed with a primary skin cancer metastasis to the spine have poor overall survival with the exception of those with BCC. The median duration of survival for patients who received surgical intervention alone, medical management (chemotherapy and/or radiation) alone, or the combination of therapies was similar across interventions. Age, spinal region, and neurological status may be associated with poor survival following surgery. PMID- 26544596 TI - A novel surgical approach to the lumbar spine involving hemilateral split-off of the spinous process to preserve the multifidus muscle: technical note. AB - In the conventional posterior approach to the lumbar spine, the lamina is exposed by stripping the paravertebral muscles from the spinous process, and the resulting paravertebral muscle damage can produce muscle atrophy and decreased muscle strength. The author developed a novel surgical approach to the lumbar spine in which the attachment of the paravertebral muscles to the spinous process is preserved. In the novel approach, the spinous process is split on the midline without stripping the attached muscles, and a hemilateral half of the spinous process is then resected at the base, exposing only the ipsilateral lamina. Before closing, the resected half is sutured and reattached to the remaining half of the spinous process. Thirty-eight patients with lumbar spinal canal stenosis (LSCS) undergoing unilateral partial laminectomy and bilateral decompression using this novel approach were analyzed. Postoperative changes in the multifidus muscle were evaluated by T2 signal intensity on MR images. MRI performed 1 year after the operation revealed no significant difference in the T2 signal intensity of the multifidus muscle between the approach and nonapproach sides. This result indicated that postoperative changes of the multifidus muscle on the approach side were slight. The clinical outcomes of unilateral partial laminectomy and bilateral decompression using this approach for LSCS were satisfactory. The novel approach can be a useful alternative to the conventional posterior lumbar approach. PMID- 26544594 TI - Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle. AB - The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naive controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission. PMID- 26544597 TI - Paraplegia after contrast media application: a transient or devastating rare complication? Case report. AB - The authors report the case of a 76-year-old man with a spinal dural arteriovenous fistula. The patient suffered from sudden repeated reversible paraplegia after spinal digital subtraction angiography as well as CT angiography. Neurotoxicity of contrast media (CM) is the most probable cause for this repeated short-lasting paraplegia. Intolerance to toxicity of CM to the vulnerable spinal cord is rare, and probably depends on the individual patient. This phenomenon is transient and can occur after both intraarterial and intravenous CM application. PMID- 26544599 TI - Nutrition in Cancer. AB - In cancer patients, oral nutrition is the preferred route of feeding since it is a significant part of the patient's daily routine and contributes to the patient's autonomy. It represents a privileged time to spend with family and friends, avoiding the tendency for isolation in these patients. The acknowledgement that the prescribed diet is individualized, adapted and adequate to individual needs empowers the patient with a feeling of control, and thus it is also a highly effective approach of psychological modulation. All these factors may potentially contribute to improve the patient's quality of life and may modulate treatment morbidity. The referral to a nutrition professional responsible for the individualized dietary counseling should always be based on evidence-based decision-making plans. The implementation of individualized nutritional counseling should consider the common causes for a poor nutritional intake in elderly cancer patients. A proper approach through counseling requires professionals with specific experience in both nutrition and oncology. Oral nutritional supplements are a simple and practical way to meet nutritional requirements when normal food intake is compromised. Ideally, oral nutritional supplements should be in addition to and not instead of meals. Supplements should be administered at a time which does not interfere with the appetite of the patient. The administration after the meal theoretically potentiates the anabolic effect on protein metabolism. Supplements with high energy density (>1 kcal/ml) or enriched with omega-3 fatty acid are probably the most effective. PMID- 26544598 TI - FESetup: Automating Setup for Alchemical Free Energy Simulations. AB - FESetup is a new pipeline tool which can be used flexibly within larger workflows. The tool aims to support fast and easy setup of alchemical free energy simulations for molecular simulation packages such as AMBER, GROMACS, Sire, or NAMD. Post-processing methods like MM-PBSA and LIE can be set up as well. Ligands are automatically parametrized with AM1-BCC, and atom mappings for a single topology description are computed with a maximum common substructure search (MCSS) algorithm. An abstract molecular dynamics (MD) engine can be used for equilibration prior to free energy setup or standalone. Currently, all modern AMBER force fields are supported. Ease of use, robustness of the code, and automation where it is feasible are the main development goals. The project follows an open development model, and we welcome contributions. PMID- 26544600 TI - Usefulness of the Macruz Index for Predicting Successful Percutaneous Mitral Balloon Valvuloplasty in Patients with Mitral Stenosis. AB - OBJECTIVE: The aim of this study was to determine whether the Macruz index (P/P-R segment) could predict the severity of valvular involvement and the success of percutaneous mitral balloon valvuloplasty (PMBV) in patients with mitral stenosis (MS). SUBJECTS AND METHODS: Sixty-one patients with MS eligible for PMBV and 72 healthy subjects (61 females and 11 males) with sinus rhythm were enrolled into this study. PMBV was performed in all patients using a percutaneous transseptal antegrade approach and a multitrack balloon technique. The P/P-R segment ratio and echocardiographic variables were measured before and 48-72 h after the procedure. The optimal cutoff point for differences in the Macruz index to determine clinical success was evaluated by receiver operating characteristic analysis by calculating the area under the curve as giving the maximum sum of sensitivity and specificity for the significant test. RESULTS: In the patient group (mean age 42.9 +/- 11.1 years), the preprocedural Macruz index was significantly higher than in the control group (2.79 +/- 1.03 vs. 1.29 +/- 0.11; p < 0.001). In the successful-procedure group (n = 53), the mean postindex value was significantly lower (2.12 +/- 0.71 vs. 2.81 +/- 1.0, p = 0.020), and the decrease in the Macruz index was significantly higher than in the unsuccessful procedure group (p = 0.007). An index decrease of 0.105 was the best cutoff value to distinguish the successful-PMBV group from the unsuccessful- PMBV group (area under the curve = 0.888, 95% confidence interval 0.788-0.988, p < 0.001). CONCLUSION: The Macruz index was significantly higher in patients with MS compared to healthy subjects. A greater decrease in the Macruz index was associated with a successful PMBV. PMID- 26544601 TI - Who Tweets with Their Location? Understanding the Relationship between Demographic Characteristics and the Use of Geoservices and Geotagging on Twitter. AB - In this paper we take advantage of recent developments in identifying the demographic characteristics of Twitter users to explore the demographic differences between those who do and do not enable location services and those who do and do not geotag their tweets. We discuss the collation and processing of two datasets-one focusing on enabling geoservices and the other on tweet geotagging. We then investigate how opting in to either of these behaviours is associated with gender, age, class, the language in which tweets are written and the language in which users interact with the Twitter user interface. We find statistically significant differences for both behaviours for all demographic characteristics, although the magnitude of association differs substantially by factor. We conclude that there are significant demographic variations between those who opt in to geoservices and those who geotag their tweets. Not withstanding the limitations of the data, we suggest that Twitter users who publish geographical information are not representative of the wider Twitter population. PMID- 26544602 TI - Music-induced emotions can be predicted from a combination of brain activity and acoustic features. AB - It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,p<0.001. This regression fit suggests that over 20% of the variance of the participant's music induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). PMID- 26544603 TI - The influence of action possibility and end-state comfort on motor imagery of manual action sequences. AB - It has been proposed that the preparation of goal-direct actions involves internal movement simulation, or motor imagery. Evidence suggests that motor imagery is critically involved in the prediction of action consequences and contributes heavily to movement planning processes. The present study examined whether the sensitivity towards end-state comfort and the possibility/impossibility to perform an action sequence are considered during motor imagery. Participants performed a mental rotation task in which two images were simultaneously presented. The image on the left depicted the start posture of a right hand when grasping a bar, while the right image depicted the hand posture at the end of the action sequence. The right image displayed the bar in a vertical orientation with the hand in a comfortable (thumb-up) or in an uncomfortable (thumb-down) posture, while the bar in the left image was rotated in picture plane in steps of 45 degrees . Crucially, the two images formed either a physically possible or physically impossible to perform action sequence. Results revealed strikingly different response time patterns for the two action sequence conditions. In general, response times increased almost monotonically with increasing angular disparity for the possible to perform action sequences. However, slight deviations from this monotonicity were apparent when the sequences contained an uncomfortable as opposed to a comfortable final posture. In contrast, for the impossible sequences, response times did not follow a typical mental rotation function, but instead were uniformly very slow. These findings suggest that both biomechanical constraints (i.e., end-state comfort) and the awareness of the possibility/impossibility to perform an action sequence are considered during motor imagery. We conclude that motor representations contain information about the spatiotemporal movement organization and the possibility of performing an action, which are crucially involved in anticipation and planning of action sequences. PMID- 26544604 TI - Activity of Caudate Nucleus Neurons in a Visual Fixation Paradigm in Behaving Cats. AB - Beside its motor functions, the caudate nucleus (CN), the main input structure of the basal ganglia, is also sensitive to various sensory modalities. The goal of the present study was to investigate the effects of visual stimulation on the CN by using a behaving, head-restrained, eye movement-controlled feline model developed recently for this purpose. Extracellular multielectrode recordings were made from the CN of two cats in a visual fixation paradigm applying static and dynamic stimuli. The recorded neurons were classified in three groups according to their electrophysiological properties: phasically active (PAN), tonically active (TAN) and high-firing (HFN) neurons. The response characteristics were investigated according to this classification. The PAN and TAN neurons were sensitive primarily to static stimuli, while the HFN neurons responded primarily to changes in the visual environment i.e. to optic flow and the offset of the stimuli. The HFNs were the most sensitive to visual stimulation; their responses were stronger than those of the PANs and TANs. The majority of the recorded units were insensitive to the direction of the optic flow, regardless of group, but a small number of direction-sensitive neurons were also found. Our results demonstrate that both the static and the dynamic components of the visual information are represented in the CN. Furthermore, these results provide the first piece of evidence on optic flow processing in the CN, which, in more general terms, indicates the possible role of this structure in dynamic visual information processing. PMID- 26544605 TI - Correction: Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation. PMID- 26544606 TI - Brands and Inhibition: A Go/No-Go Task Reveals the Power of Brand Influence. AB - Whether selecting a candy in a shop or picking a digital camera online, there are usually many options from which consumers may choose. With such abundance, consumers must use a variety of cognitive, emotional, and heuristic means to filter out and inhibit some of their responses. Here we use brand logos within a Go/No-Go task to probe inhibitory control during the presentation of familiar and unfamiliar logos. The results showed no differences in response times or in commission errors (CE) between familiar and unfamiliar logos. However, participants demonstrated a generally more cautious attitude of responding to the familiar brands: they were significantly slower and less accurate at responding to these brands in the Go trials. These findings suggest that inhibitory control can be exercised quite effectively for familiar brands, but that when such inhibition fails, the potent appetitive nature of brands is revealed. PMID- 26544608 TI - Pure oats as part of the gluten-free diet in celiac disease: The need to revisit the issue. PMID- 26544607 TI - Insular Gray Matter Volume and Objective Quality of Life in Schizophrenia. AB - Improving quality of life has been recognized as an important outcome for schizophrenia treatment, although the fundamental determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and objective quality of life in schizophrenia patients. Thirty-three schizophrenia patients and 42 age-, sex-, and education-matched healthy participants underwent magnetic resonance imaging. The Quality of Life Scale was used to measure objective quality of life in schizophrenia patients. Voxel-based morphometry was performed to identify regional brain alterations that correlate with Quality of Life Scale score in the patient group. Schizophrenia patients showed gray matter reductions in the frontal, temporal, limbic, and subcortical regions. We then performed voxel-based multiple regression analysis in these regions to identify any correlations between regional gray matter volume and Quality of Life Scale scores. We found that among four subcategories of the scale, the Instrumental Role category score correlated with gray matter volume in the right anterior insula in schizophrenia patients. In addition, this correlation was shown to be mediated by negative symptoms. Our findings suggest that the neural basis of objective quality of life might differ topographically from that of subjective QOL in schizophrenia. PMID- 26544609 TI - Similar Squamous Cell Carcinoma Epithelium microRNA Expression in Never Smokers and Ever Smokers. AB - The incidence of oral tumors in patients who never used mutagenic agents such as tobacco is increasing. In an effort to better understand these tumors we studied microRNA (miRNA) expression in tumor epithelium of never tobacco users, tumor epithelium of ever tobacco users, and nonpathological control oral epithelium. A comparison of levels among 372 miRNAs in 12 never tobacco users with oral squamous cell carcinoma (OSCC) versus 10 healthy controls was made using the reverse transcription quantitative polymerase chain reaction. A similar analysis was done with 8 ever tobacco users with OSCC. These comparisons revealed miR-10b 5p, miR-196a-5p, and miR-31-5p as enriched in the tumor epithelium in OSCC of both never and ever tobacco users. Examination of The Cancer Genome Atlas (TCGA) project miRNA data on 305 OSCCs and 30 controls revealed 100% of those miRNAs enriched in never smoker OSCCs in this patient group were also enriched in ever smoker OSCCs. Nonsupervised clustering of TCGA OSCCs was suggestive of two or four subgroups of tumors based on miRNA levels with limited evidence for differences in tobacco exposure among the groups. Results from both patient groups together stress the importance of miR196a-5p in OSCC malignancy in both never and ever smokers, and emphasize the overall similarity of miRNA expression in OSCCs in these two risk groups. It implies that there may be great similarity in etiology of OSCC in never and ever smokers and that classifying OSCC based on tobacco exposure may not be helpful in the clinic. PMID- 26544610 TI - Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. AB - BACKGROUNDS: Several cross-sectional studies suggested a link between endometriosis and mood disorders. However, the temporal association between endometriosis and mood disorders (depression and anxiety disorders) is still unclear. METHODS: Using the Taiwan National Health Insurance Research Database, 10,439 women with endometriosis and 10,439 (1:1) age-/sex-matched controls between 1998 and 2009 were enrolled, and followed up to the end of 2011. Those who developed depression or anxiety disorders during the follow-up were identified. RESULTS: Women with endometriosis had an increased risk of developing major depression (hazard ratio [HR]: 1.56, 95% confidence interval [CI]:1.24 1.97), any depressive disorder (HR: 1.44, 95% CI: 1.25-1.65), and anxiety disorders (HR: 1.44, 95% CI: 1.22-1.70) in later life compared to those without endometriosis. Stratified by age group, women with endometriosis aged <40 years and those aged ?40 years were both prone to developing major depression (HR: 1.52, 95% CI: 1.15-1.99; HR: 1.69, 95% CI: 1.09-2.62), any depressive disorder (HR: 1.43, 95% CI: 1.21-1.69; HR: 1.45, 95% CI: 1.13-1.56), and anxiety disorders (HR: 1.39, 95% CI: 1.14-1.71; HR: 1.53, 95% CI: 1.15-2.04). LIMITATION: the incidence of depression and anxiety disorders may be underestimated since only those who sought medical consultation and help would be enrolled in our study. CONCLUSION: Endometriosis was associated with an elevated likelihood of developing depression and anxiety disorders. Further studies may be required to investigate the underlying pathophysiology between endometriosis and both depression and anxiety disorders. PMID- 26544611 TI - Cannabis use disorder is associated with greater illness severity in tobacco smoking patients with bipolar disorder. AB - OBJECTIVE: Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients. METHODS: A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses. RESULTS: In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant. LIMITATIONS: Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for. CONCLUSION: Studies have found associations between tobacco smoking and poorer outcomes in BD. In this study on tobacco smoking BD patients we report an association between CUD and illness severity, suggesting that CUD exacerbates the disease evolution independently of tobacco smoking. Specific treatment and prevention programs addressing CUD in BD patients are warranted. PMID- 26544612 TI - Childhood motor coordination and adult psychopathology in extremely low birth weight survivors. AB - OBJECTIVE: To determine if childhood motor coordination is associated with lifetime major depressive disorder (MDD), current generalized anxiety disorder (GAD), and attention-deficit/hyperactivity disorder (ADHD) in adulthood, and to examine if extremely low birth weight (ELBW; <1000 g) status moderates the strength of these associations. METHOD: Prospective study of a cohort of normal birth weight (NBW) controls and ELBW survivors. Participants completed the short form Bruininks-Oseretsky Test of Motor Proficiency (BOTMP-SF) at age 8. At age 29 36, participants completed the Mini International Neuropsychiatric Interview to diagnose the psychiatric disorders of interest. RESULTS: Birth weight status significantly influenced the strength and direction of associations between childhood motor coordination and adult psychiatric outcomes such that the odds of MDD (Pinteraction=.02) and GAD (Pinteraction=.01) increased with worsening motor scores in NBW adults but not ELBW survivors. Stratified analyses indicated that in NBW adults, for each one-point decrease in BOTMP-SF score, the odds of lifetime MDD increased by 10% (OR=1.10, 95% CI: 1.01-1.20). LIMITATIONS: Participant attrition reduced sample size and that may have limited our ability to detect statistically significant results for some of our analyses. CONCLUSION: Poorer motor coordination in early life has a negative long-term impact on the development of MDD and GAD of individuals born at NBW. The long-term mental health risks of childhood motor coordination problems are significant and highlight the importance of recognizing motor deficits in all children, so that associated psychological difficulties can be identified and treated at an early age. PMID- 26544613 TI - Low stability of diagnostic classifications of anxiety disorders over time: A six year follow-up of the NESDA study. AB - BACKGROUND: Stability of diagnosis was listed as an important predictive validator for maintaining separate diagnostic classifications in DSM-5. The aim of this study is to examine the longitudinal stability of anxiety disorder diagnoses, and the difference in stability between subjects with a chronic versus a non-chronic course. METHODS: Longitudinal data of 447 subjects with a current pure anxiety disorder diagnosis at baseline from the Netherlands Study of Depression and Anxiety were used. At baseline, 2-, 4-, and 6-year follow-up mental disorders were assessed and numbers (and percentages) of transitions from one anxiety disorder diagnosis to another were determined for each anxiety disorder diagnosis separately and for subjects with a chronic (i.e. one or more anxiety disorder at every follow-up assessment) and a non-chronic course. RESULTS: Transition percentages were high in all anxiety disorder diagnoses, ranging from 21.1% for social anxiety disorder to 46.3% for panic disorder with agoraphobia at six years of follow-up. Transition numbers were higher in the chronic than in the non-chronic course group (p=0.01). LIMITATIONS: Due to the 2 year sample frequency, the number of subjects with a chronic course may have been overestimated as intermittent recovery periods may have been missed. CONCLUSIONS: These data indicate that anxiety disorder diagnoses are not stable over time. The validity of the different anxiety disorder categories is not supported by these longitudinal patterns, which may be interpreted as support for a more pronounced dimensional approach to the classification of anxiety disorders. PMID- 26544614 TI - Occupational differences in suicide mortality among Japanese men of working age. AB - BACKGROUND: Although suicide rates among Japanese men of working-age have steadily increased over the past two decades, the distribution by occupation and industry is not uniform. Little is known regarding occupation and industry differences in relation to suicide risk. This study examined differences in suicide risk among Japanese men of working age (25-59 years) during 2010. METHODS: We analysed the Japanese government's 2010 national survey data regarding occupation and industry-specific death rates. Poisson regression models were formulated for each occupation and industry to estimate the relative risk of death by suicide. Potential interactions between age and occupation/industry were also examined. RESULTS: Suicide incidence was highest among workers in the fields of agriculture and mining. When compared with referent groups (sales for occupation and wholesale and retail for industry), the age-adjusted relative risk of suicide was highest for administrative and managerial workers (Incident Relative Risk [IRR]: 3.91, 95% Confidence Interval [95%CI]: 3.16-4.85), service industries (IRR: 3.63, 95%CI: 2.93-4.51) and agriculture (IRR: 3.53, 95%CI: 2.84 4.38) occupations, and for mining (IRR: 23.9, 95%CI: 19.4-29.4), fisheries (IRR: 6.26, 95%CI: 5.03-7.80), electricity and gas (IRR: 5.86, 95%CI: 4.71-7.30) and agricultural industries (IRR: 4.73, 95%CI: 3.78-5.91). LIMITATIONS: Bias resulting from misclassification of deceased individuals' occupation or industry was a potential limitation of this study. Furthermore, detailed information regarding occupation-related factors, such as employment status, had not been recorded in the initial survey. CONCLUSIONS: These findings help elucidate Japanese occupations and industries with a higher suicide risk, most likely due to economic changes or workplace factors relating to stress and depression. PMID- 26544616 TI - A haplotype in the 5'-upstream region of the NDUFV2 gene is associated with major depressive disorder in Han Chinese. AB - BACKGROUND: There is ample evidence supporting the idea that mitochondrial dysfunction and altered expression of complex I subunits play important roles in the pathophysiology of mental disorders. Early literature reports have implicated NDUFV2, a nuclear-encoded mitochondrial complex I subunit gene, in bipolar disorder and schizophrenia. There has been no genetic study to investigate whether there is an association between NDUFV2 and major depressive disorder (MDD). METHODS: This study recruited 744 patients with MDD and 767 well-matched healthy controls in a Chinese Han population, and genotyped 9 SNPs within NDUFV2. RESULTS: Initial analysis showed statistically significant differences for 2 SNPs (rs4798765 and rs12964485) in the genotypic distribution and for 1 SNP (rs4797356) in the allelic distribution between the case and control groups. Nevertheless, no significance was demonstrated following multiple testing corrections. Haplotype analysis showed that the T-C haplotype, consisting of rs12457810 and rs12964485, was significantly associated with MDD (P=0.005, corrected P=0.04 after a 10,000 permutation test). We performed an eQTL analysis and found that rs12964485 was significantly associated with NDUFV2 expression in the occipital cortex (P=0.036), albeit this significance did not survive after Bonferroni correction. LIMITATION: This is a preliminary investigation with a relatively modest sample size. CONCLUSION: Our findings provided preliminary evidence that a haplotype T-C consisting of rs12457810 and rs12964485 in the 5' upstream region of NDUFV2 may be a protective factor for the development of MDD in Han Chinese. PMID- 26544615 TI - Ongoing life stressors and suicidal ideation among HIV-infected adults with depression. AB - BACKGROUND: Suicidal ideation is the most proximal risk factor for suicide and can indicate extreme psychological distress; identification of its predictors is important for possible intervention. Depression and stressful or traumatic life events (STLEs), which are more common among HIV-infected individuals than the general population, may serve as triggers for suicidal thoughts. METHODS: A randomized controlled trial testing the effect of evidence-based decision support for depression treatment on antiretroviral adherence (the SLAM DUNC study) included monthly assessments of incident STLEs, and quarterly assessments of suicidal ideation (SI). We examined the association between STLEs and SI during up to one year of follow-up among 289 Southeastern US-based participants active in the study between 7/1/2011 and 4/1/2014, accounting for time-varying confounding by depressive severity with the use of marginal structural models. RESULTS: Participants were mostly male (70%) and black (62%), with a median age of 45 years, and experienced a mean of 2.36 total STLEs (range: 0-12) and 0.48 severe STLEs (range: 0-3) per month. Every additional STLE was associated with an increase in SI prevalence of 7% (prevalence ratio (PR) (95% confidence interval (CI)): 1.07 (1.00, 1.14)), and every additional severe STLE with an increase in SI prevalence of 19% (RR (95% CI): 1.19 (1.00, 1.42)). LIMITATIONS: There was a substantial amount of missing data and the exposures and outcomes were obtained via self-report; methods were tailored to address these potential limitations. CONCLUSIONS: STLEs were associated with increased SI prevalence, which is an important risk factor for suicide attempts and completions. PMID- 26544617 TI - A systematic review of the factor structure and reliability of the Spence Children's Anxiety Scale. AB - BACKGROUND: The Spence Children's Anxiety Scale (SCAS) is a widely used instrument for assessing symptoms of anxiety disorders among children and adolescents. Previous studies have demonstrated its good reliability for children and adolescents from different backgrounds. However, remarkable variability in the reliability of the SCAS across studies and inconsistent results regarding its factor structure has been found. METHODS: The present study aims to examine the SCAS factor structure by means of a systematic review with narrative synthesis, the mean reliability of the SCAS by means of a meta-analysis, and the influence of the moderators on the SCAS reliability. Databases employed to collect the studies included Scholar Google, PsycARTICLES, PsycINFO, Web of Science, and Scopus since 1997. RESULTS: Twenty-nine and 32 studies, which examined the factor structure and the internal consistency of the SCAS, respectively, were included. The SCAS was found to have strong internal consistency, influenced by different moderators. The systematic review demonstrated that the original six-factor model was supported by most studies. LIMITATIONS: Factorial invariance studies (across age, gender, country) and test-retest reliability of the SCAS were not examined in this study. CONCLUSIONS: It is concluded that the SCAS is a reliable instrument for cross-cultural use, and it is suggested that the original six factor model is appropriate for cross-cultural application. PMID- 26544618 TI - Psychological distress during pregnancy in Miyagi after the Great East Japan Earthquake: The Japan Environment and Children's Study. AB - OBJECTIVE: To examine psychological distress among pregnant women in Miyagi prefecture which was directly affected by the Great East Japan Earthquake and tsunami and compare other areas of Japan that were less damaged. METHODS: This study was conducted in conjunction with the Japan Environment and Children's Study (JECS). We examined 10,129 Japanese women using the primary fixed data of the JECS. The Kessler 6-item psychological distress scale (K6) was administered to 7473 eligible women including 998 in Miyagi unit center ('Miyagi UC') and 6475 in the other unit centers ('13UCs'). We compared the prevalence and the risk of distress (K6 >= 13) during pregnancy in 'Miyagi UC' and '13UCs'. RESULTS: More women in 'Miyagi UC' (4.9%) suffered psychological distress, compared with '13UCs' (3.1%) (p<0.001). A significantly higher prevalence of women in 'Miyagi UC' (55.5%) had experienced negative life events, whereas '13UCs' showed 42.7% (p<0.0001). In multivariable logistic analyses adjusted for baseline characteristics, there was a significant regional difference of psychological distress (adjusted odds ratio; aOR in Miyagi UC=1.488; 95%CI, 1.059-2.090). After further adjusting for negative life events, the association was diminished (aOR=1.338; 95%CI, 0.949-1.884). LIMITATIONS: The JECS had no data before the earthquake and the extent of damage was not investigated. Possible regional representativeness is also a limitation. CONCLUSION: After the Great East Japan Earthquake, the prevalence of pregnant women with psychological distress (K6 >= 13) were high in Miyagi prefecture. Especially in the coastal area directly affected by tsunami, it is high with or without negative life events experienced. PMID- 26544619 TI - The relationship between anxiety disorders and dimensional representations of DSM IV personality disorders: A co-twin control study. AB - BACKGROUND: There is substantial comorbidity between personality disorders (PDs) and anxiety disorders (ADs). Sharing of familial risk factors possibly explains the co-occurrence, but direct causal relationships between the disorders may also exist. METHODS: 2801 persons from 1391 twin pairs from the Norwegian Institute of Public Health Twin Panel were assessed for all DSM-IV PDs and ADs. Bivariate Poisson-regression analyses were performed to assess whether PDs predicted ADs at three different levels: All PDs combined, PDs combined within DSM-IV-clusters and each individual PD separately. Next, bivariate co-twin control analyses were executed within monozygotic (MZ) and dizygotic (DZ) twin pairs. A similar analytic strategy was employed in multivariate models including PDs as independent variables. RESULTS: PDs predicted ADs at all levels of analysis in bivariate regression models. Bivariate co-twin control analyses demonstrated an increased risk of ADs in all PDs combined, all PD-clusters and in schizotypal, paranoid, borderline, antisocial, avoidant and dependent PD. In the multivariate regression model, all PD-clusters and schizotypal, borderline, avoidant and obsessive-compulsive PD predicted ADs. Only borderline and avoidant PD predicted ADs in the multivariate co-twin control analysis. LIMITATIONS: Over-adjustment may explain the results from the multivariate analyses. The cross-sectional study design hampers causal inference. CONCLUSIONS: Comorbidity between ADs and PDs can be largely accounted for by shared familial risk factors. However, the results are also consistent with a direct causal relationship partly explaining the co occurrence. Our results indicate specific environmental factors for comorbidity of ADs and borderline and avoidant PDs that are not shared with other PDs. PMID- 26544620 TI - A comparative cross-cultural study of the prevalence of late life depression in low and middle income countries. AB - BACKGROUND: Current estimates of the prevalence of depression in later life mostly arise from studies carried out in Europe, North America and Asia. In this study we aimed to measure the prevalence of depression using a standardised method in a number of low and middle income countries (LMIC). METHODS: A one phase cross-sectional survey involving over 17,000 participants aged 65 years and over living in urban and rural catchment areas in 13 sites from 9 countries (Cuba, Dominican Republic, Puerto Rico, Mexico, Venezuela, Peru, China, India and Nigeria). Depression was assessed and compared using ICD-10 and EURO-D criteria. RESULTS: Depression prevalence varied across sites according to diagnostic criteria. The lowest prevalence was observed for ICD-10 depressive episode (0.3 to 13.8%). When using the EURO-D depression scale, the prevalence was higher and ranged from 1.0% to 38.6%. The crude prevalence was particularly high in the Dominican Republic and in rural India. ICD-10 depression was also associated with increased age and being female. LIMITATIONS: Generalisability of findings outside of catchment areas is difficult to assess. CONCLUSIONS: Late life depression is burdensome, and common in LMIC. However its prevalence varies from culture to culture; its diagnosis poses a significant challenge and requires proper recognition of its expression. PMID- 26544621 TI - Emergence of High-Level Daptomycin Resistance in Corynebacterium striatum in Two Patients with Left Ventricular Assist Device Infections. AB - INTRODUCTION: We describe the clinical and microbiologic courses of two patients with ventricular assist device infections secondary to Corynebacterium striatum treated with daptomycin. In both cases, the pathogen was initially susceptible to daptomycin (minimum inhibitory concentration [MIC] <0.125 mg/L) but became resistant (MIC >256 mg/L) during therapy. METHODS: The clonal nature of the isolates was determined by pulse-field gel electrophoresis (PFGE). Daptomycin binding was assessed by fluorescence microscopy using daptomycin-boron dipyrromethene (bodipy). Induction and stability of daptomycin resistance were assessed by culturing strains in the presence of low concentrations of daptomycin or passage of resistant strains on daptomycin-free medium and repeat MIC testing, respectively. RESULTS: PFGE revealed that resistant clinical isolates were genetically indistinguishable from their parent strains, but the two pairs were unrelated to each other. The resistant strains had 7.5-15 times lower binding of daptomycin-bodipy compared to the related susceptible strains (p <= 0.0002). High level daptomycin resistance (MIC >256 mg/L) was generated in vitro for both susceptible parent strains after overnight culture in the presence of daptomycin. One of the resistant strains maintained a high-level resistance phenotype up to 5 days of passage on daptomycin-free medium, whereas the other strain reverted back to a susceptible phenotype (MIC = 0.38 mg/L) after one passage on daptomycin-free medium, with a concomitant increase in daptomycin binding. CONCLUSIONS: High level daptomycin resistance in C. striatum was readily generated in vitro and during the course of therapy in these patients. This resistance appears to be mediated by reduced daptomycin binding. Providers should be cautious about using long-term daptomycin monotherapy for C. striatum infections. PMID- 26544622 TI - Comparing the clinical outcomes in stereotactic body radiotherapy for lung tumors between Ray-Tracing and Monte-Carlo algorithms. AB - PURPOSE: The purpose of this study was to compare the clinical outcomes between the groups using Ray-Tracing (RAT) and Monte-Carlo (MC) calculation algorithms for stereotactic body radiotherapy (SBRT) of lung tumors. MATERIALS AND METHODS: Thirty-five patients received SBRT with CyberKnife for 47 primary or metastatic lung tumors. RAT was used for 22 targets in 12 patients, and MC for 25 targets in 23 patients. Total dose of 48 to 60 Gy was prescribed in 3 to 5 fractions on median 80% isodose line. The response rate, local control rate, and toxicities were compared between RAT and MC groups. RESULTS: The response rate was lower in the RAT group (77.3%) compared to the MC group (100%) (p = 0.008). The response rates showed an association with the mean dose to the gross tumor volume, which the doses were re-calculated with MC algorithm in both groups. However, the local control rate and toxicities did not differ between the groups. CONCLUSIONS: The clinical outcome and toxicity of lung SBRT between the RAT and MC groups were similar except for the response rate when the same apparent doses were prescribed. The lower response rate in the RAT group, however, did not compromise the local control rates. As such, reducing the prescription dose for MC algorithm may be performed but done with caution. PMID- 26544623 TI - Cullin3 promotes breast cancer cells metastasis and epithelial-mesenchymal transition by targeting BRMS1 for degradation. AB - Metastasis is the leading cause of death in breast cancer (BC) patients. However, until now, the mechanisms of BC metastasis remain elusive. Cullin3 is a highly conserved Cullin family member present in the genomes of all eukaryotes, which has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in BC remain unclear. Here we show that Cullin3 is elevated in BC and its expression level is positively correlated with metastasis. Overexpression of Cullin3 in BC cells increased proliferation, epithelial mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing Cullin3 in aggressive and invasive BC cells inhibited these processes. Mechanistically, we found Cullin3 exerts its function through promoting BRMS1 protein degradation, which was associated with EMT, migration and invasion. BRMS1 overexpression blocked Cullin3-driven EMT, and metastasis. Our results, for the first time, portray a pivotal role of Cullin3 in stimulating metastatic behaviors of BC cells. Targeting Cullin3 may thus be a useful strategy to impede BC cell invasion and metastasis. PMID- 26544624 TI - Enhancement of NAD+-dependent SIRT1 deacetylase activity by methylselenocysteine resets the circadian clock in carcinogen-treated mammary epithelial cells. AB - We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD+/NADH ratio and reduced NAD+-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD+/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD+-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD+/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD+/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD+-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis. PMID- 26544625 TI - Oncogenic Ras suppresses ING4-TDG-Fas axis to promote apoptosis resistance. AB - Ras is aberrantly activated in many cancers and active DNA demethylation plays a fundamental role to establish DNA methylation pattern which is of importance to cancer development. However, it was unknown whether and how Ras regulate DNA demethylation during carcinogenesis. Here we found that Ras downregulated thymine DNA glycosylase (TDG), a DNA demethylation enzyme, by inhibiting the interaction of transcription activator ING4 with TDG promoter. TDG recruited histone lysine demethylase JMJD3 to the Fas promoter and activated its expression, thus restoring sensitivity to apoptosis. TDG suppressed in vivo tumorigenicity of xenograft pancreatic cancer. Thus, we speculate that reversing Ras-mediated ING4 inhibition to activate Fas expression is a potential therapeutic approach for Ras driven cancers. PMID- 26544627 TI - Confirmatory factor analysis of the Arabic version of the Lower Extremity Functional Scale. AB - The aim of this study was to examine the factorial structure of the Arabic version of the Lower Extremity Functional Scale (LEFS-Ar) using a confirmatory factor analysis. The study was designed as a cross-sectional study in which individuals with lower extremity musculoskeletal disorders were recruited. During the testing session, participants completed the LEFS-Ar in addition to general information form and anthropometric measurements. A hypothesized one-factor structure underlying the 20 items of the LEFS-Ar was examined using a confirmatory factor analysis. The fit of the observed data to the hypothesized factorial structure was examined using multiple fit statistics including chi2, Tucker-Lewis index (TLI), comparative-fit index (CFI), and the root mean square error of approximation (RMSEA). A total of 160 patients with lower extremity dysfunctions participated in this study. The fit statistics showed the following: chi2 goodness fit statistic=654.390 (d.f.=170, P<0.001), TLI=0.754, CFI=0.78, and RMSEA=0.134 (90% CI=0.123-0.145). These fit statistics indicate that the data do fit the one-factor structure proposed in this study. Examination of standardized residuals and modification indices pointed to areas of misfit within the model. The findings of the current study do not support the hypothesized one-factor structure of the LEFS-Ar and suggest that modifications are needed to the LEFS-Ar to yield a unidimensional measure of lower extremity function (i.e. activity limitation due to lower extremity dysfunction). PMID- 26544626 TI - Molecular characterization of metastatic exon 11 mutant gastrointestinal stromal tumors (GIST) beyond KIT/PDGFRalpha genotype evaluated by next generation sequencing (NGS). AB - About 85% of GISTs are associated with KIT and PDGFRalpha gene mutations, which predict response to tyrosine kinase inhibitors. Although the outcomes in patients affected by GIST have dramatically improved, tumor progression control still remains a challenge. The aim of this study is the genomic characterization of individual metastatic KIT-exon 11-mutant GIST to identify additional aberrations and simultaneous molecular events representing potential therapeutic targets.Seven patients with metastatic GIST were studied with whole transcriptome sequencing and copy number analysis. Somatic single nucleotide variations were called; however, no shared mutated genes were detected except KIT. Almost all patients showed loss of genomic regions containing tumor suppressor genes, sometimes coupled with single nucleotide mutation of the other allele. Additionally, six fusion transcripts were found and three patients showed amplifications involving known oncogenes.Evaluating the concordance between CN status and mRNA expression levels, we detected overexpression of CCND2 and EGFR and silencing of CDKN2A, CDKN2C, SMARCB1, PTEN and DMD. Altered expression of these genes could be responsible for aberrant activation of signaling pathways that support tumor growth. In this work, we assessed the effect of Hedgehog pathway inhibition in GIST882 cells, which causes decrement of cell viability associated with reduction of KIT expression.Additional genomic alterations not previously reported in GIST were found even if not shared by all samples. This contributes to a more detailed molecular understanding of this disease, useful for identification of new targets and novel therapeutics and representing a possible point of departure for a truly individualized clinical approach. PMID- 26544628 TI - Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes. AB - BACKGROUND/AIMS: Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process. METHODS: First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBPalpha after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/beta catenin pathway in TSCs. RESULTS: Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3beta (P-GSK 3 beta (ser9)), upregulated P-GSK-3beta (tyr216), and downregulated the pivotal signaling molecule beta-catenin. Furthermore, DKK1 knockdown attenuated Dex induced inhibition of the canonical WNT/beta-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3beta inhibitor) reduced Dex-induced inhibition of the classical WNT/beta-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes. CONCLUSION: In conclusion, by upregulating DKK1 expression, reducing the level of P-GSK-3beta (ser9), and increasing the level of P-GSK-3beta (tyr216), Dex causes the degradation of beta-catenin, the central molecule of the classical WNT pathway, thereby inducing rat TSCs to differentiate into adipocytes. PMID- 26544629 TI - Structure activity relationships of 4-hydroxy-2-pyridones: A novel class of antituberculosis agents. AB - Pyridone 1 was identified from a high-throughput cell-based phenotypic screen against Mycobacterium tuberculosis (Mtb) including multi-drug resistant tuberculosis (MDR-TB) as a novel anti-TB agent and subsequently optimized series using cell-based Mtb assay. Preliminary structure activity relationship on the isobutyl group with higher cycloalkyl groups at 6-position of pyridone ring has enabled us to significant improvement of potency against Mtb. The lead compound 30j, a dimethylcyclohexyl group on the 6-position of the pyridone, displayed desirable in vitro potency against both drug sensitive and multi-drug resistant TB clinical isolates. In addition, 30j displayed favorable oral pharmacokinetic properties and demonstrated in vivo efficacy in mouse model. These results emphasize the importance of 4-hydroxy-2-pyridones as a new chemotype and further optimization of properties to treat MDR-TB. PMID- 26544630 TI - Analogues of ethionamide, a drug used for multidrug-resistant tuberculosis, exhibit potent inhibition of tyrosinase. AB - Tyrosinase catalyzes two distinct sequential reactions in melanin biosynthesis: the hydroxylation of tyrosine to DOPA followed by the oxidation of DOPA to dopaquinone. The central roles of melanin in living species have motivated researchers to maintain constant efforts to discover new agents that modulate tyrosinase activity. In this study, we report on the inhibition of tyrosinase by ethionamide and its analogues. Ethionamide, 2-ethylpyridine-4-carbothioamide, is a second-line antituberculosis drug used for the treatment of multidrug-resistant tuberculosis. The chemical similarity of ethionamide to phenylthiourea, a well known tyrosinase inhibitor, led us to investigate its inhibitory effects on mushroom tyrosinase and the IC50 was calculated as 4 MUM. Five analogues of ethionamide, including another antituberculosis drug, prothionamide, were also inhibitory, with values for IC50 in the range of 3-43 MUM. Fluorescence quenching experiments supported a mechanism of direct binding. In contrast, isoniazid, a structural analogue and first-line antituberculosis drug, was a poor inhibitor of tyrosinase. We also tested the effects of ethionamide and its analogues on melanin content in B16F10 cells. At a concentration of 50 MUM, the molecules, pyridine-2-carbothioamide and thiobenzamide substantially decreased the melanin content by 44% and 37%, respectively. In addition to identifying other interactions, docking simulations showed that the carbothioamide groups of the molecules make essential contacts with the catalytic di-copper atoms. Our results suggest that carbothioamide can be a central moiety for the development of new and potent tyrosinase inhibitors. PMID- 26544631 TI - Bilirubin oxidase based enzymatic air-breathing cathode: Operation under pristine and contaminated conditions. AB - The performance of bilirubin oxidase (BOx) based air breathing cathode was constantly monitored over 45 days. The effect of electrolyte composition on the cathode oxygen reduction reaction (ORR) output was investigated. Particularly, deactivation of the electrocatalytic activity of the enzyme in phosphate buffer saline (PBS) solution and in activated sludge (AS) was evaluated. The greatest drop in current density was observed during the first 3 days of constant operation with a decrease of ~60 MUA cm(-2) day(-1). The rate of decrease slowed to ~10 MUA cm(-2) day(-1) (day 3 to 9) and then to ~1.5 MUA cm(-2)day(-1) thereafter (day 9 to 45). Despite the constant decrease in output, the BOx cathode generated residual current after 45 days operations with an open circuit potential (OCP) of 475 mV vs. Ag/AgCl. Enzyme deactivation was also studied in AS to simulate an environment close to the real waste operation with pollutants, solid particles and bacteria. The presence of low-molecular weight soluble contaminants was identified as the main reason for an immediate enzymatic deactivation within few hours of cathode operation. The presence of solid particles and bacteria does not affect the natural degradation of the enzyme. PMID- 26544632 TI - The enhancement of friction ridge detail on brass ammunition casings using cold patination fluid. AB - Brass ammunition is commonly found at firearms related crime scenes. For this reason, many studies have focused on evidence that can be obtained from brass ammunition such as DNA, gunshot residue and fingerprints. Latent fingerprints on ammunition can provide good forensic evidence, however; fingerprint development on ammunition casings has proven to be difficult. A method using cold patination fluid is described as a potential tool to enhance friction ridge detail on brass ammunition casings. Current latent fingerprint development methods for brass ammunition have either failed to provide the necessary quality of friction ridge detail or can be very time consuming and require expensive equipment. In this study, the enhancement of fingerprints on live ammunition has been achieved with a good level of detail whilst the development on spent casings has to an extent also been possible. Development with cold patination fluid has proven to be a quick, simple and cost-effective method for fingerprint development on brass ammunition that can be easily implemented for routine police work. PMID- 26544633 TI - Technical Note: "Mitochondrial and nuclear DNA approaches for reliable identification of Lucilia (Diptera, Calliphoridae) species of forensic interest from Southern Europe". AB - In forensic entomology, rapid and unambiguous identification of blowfly species is a critical prerequisite for accurately estimating the post-mortem interval (PMI). The conventional diagnosis of cadaveric entomofauna based on external characters is hampered by the morphological similarities between species, especially in immature stages. Genetic analysis has been shown to allow precise and reliable diagnosis and delimitation of insect species. Nevertheless, the taxonomy of some species remains unresolved. This study was focused on improving the effectiveness and accuracy of analysis based on the widely used cytochrome c oxidase subunit I barcode region (COI barcode, 658 bp), complemented by other mitochondrial and nuclear regions, such as cytochrome b (Cyt-b, 307 bp) and the second internal transcribed spacer (ITS2, 310-331 bp), for the identification of Southern European blowflies. We analyzed a total of 209 specimens, collected from 38 human corpses, belonging to three Calliphoridae genera and seven species: Chrysomya (Ch. albiceps), Calliphora (C. vicina and C. vomitoria), and Lucilia (L. sericata, L. ampullacea, L. caesar and L. illustris). These species are the most common PMI indicators in Portugal. The results revealed that unambiguous separation of species of the Lucilia genus requires different loci from the barcode region. Furthermore, we conclude that the ITS2 (310-331 bp) molecular marker is a promising diagnostic tool because its inter-specific discriminatory power enables unequivocal and consistent distinctions to be made, even between closely related species (L. caesar-L. illustris). This work also contributes new genetic data that may be of interest in performing species diagnosis for Southern European blowflies. Notably, to the best of our knowledge, we provide the first records of the Cyt-b (307 bp) locus for L. illustris and the ITS2 (310-331 bp) region for Iberian Peninsula Lucilia species. PMID- 26544634 TI - Benefit of Contrast-Enhanced Ultrasound (CEUS) in the Follow-Up Care of Patients with Colon Cancer: A Prospective Multicenter Study. AB - PURPOSE: According to the German guidelines on colorectal cancer, unenhanced ultrasound is recommended for follow-up. On the other hand, ultrasound and radiology societies specify the use of contrast-enhanced ultrasound for ruling out liver metastases. Studies focusing on the follow-up of cancer patients are lacking. The goal of this multicenter study initiated by the German Ultrasound Society (DEGUM) was to determine the potential benefit of contrast-enhanced ultrasound in the follow-up of patients with colon cancer. MATERIALS AND METHODS: Follow-up patients with colon cancer (UICC > IIa) were investigated. As scheduled according to the German guidelines, unenhanced ultrasound was performed followed by contrast-enhanced ultrasound. All liver lesions were recorded. In case of additional metastases detected on contrast-enhanced ultrasound, contrast-enhanced CT, MRI or biopsy was performed to confirm additional liver metastases. RESULTS: A total of 45 liver metastases were detected in 26/290 patients (= 9 %) using unenhanced ultrasound. A further 28 metastases were detected on contrast-enhanced ultrasound in these 26 patients. In 18 patients showing no liver metastases, 40 additional metastases were detected on unenhanced ultrasound. This means that 44 patients with a total of 113 liver metastases were detected on contrast-enhanced ultrasound (p = 0.0006). CONCLUSION: Contrast-enhanced ultrasound should be recommended in the follow-up of patients with colon cancer in addition to unenhanced ultrasound - the up-to-date standard. PMID- 26544635 TI - Noninvasive Testing in Emergency Department Patients with Low-Risk Chest Pain: Does the Evidence Support Current Guidelines? AB - Patients who present to the emergency department with chest pain but no evidence of ischemia on the electrocardiogram and negative cardiac markers are at very low risk. The newest American Heart Association/American College of Cardiology guidelines give noninvasive cardiac testing a IIa recommendation in this patient population. Here, we will review the existing literature that was cited in the American Heart Association/American College of Cardiology document, as well as several large, contemporary, comparative observational studies which were not included to address the following question: Do the benefits of noninvasive cardiac testing in this patient population outweigh the risks? PMID- 26544636 TI - Bottlebrush Block Polymers: Quantitative Theory and Experiments. AB - The self-assembly of bottlebrush block polymers into a lamellar phase was investigated using a combination of experiment and self-consistent field theory (SCFT). Nine diblock bottlebrush polymers were synthesized with atactic polypropylene side chains (block A) and polystyrene side chains (block B) attached to poly(norbornene) backbones of various contour lengths, L, and the resulting lamellar structures were analyzed using small-angle X-ray scattering. The scaling of the lamellar period, d0 ~ L(gamma), exhibited an increasing exponent from gamma ~ 0.3 at small L to gamma ~ 0.9 at large L. The small exponents occurred for starlike molecules where the size of the side chains is comparable to L, while the larger exponents occurred for the more brushlike molecules where the side chains extend radially outward from the backbone. The bottlebrushes were then modeled using flexible side chains of types A and B attached to a semiflexible backbone with an adjustable persistence length, xib. The resulting SCFT predictions for d0 showed remarkable quantitative agreement with the experimental data, where xib was similar to the radius of the bottlebrushes. The theory was then used to examine the joint-distribution functions for the position and orientation of different segments along the backbone. This revealed a bilayer arrangement of the bottlebrushes in the lamellar phase, with a high degree of backbone orientation at the A/B interfaces that almost completely vanished near the center of the domains. This finding clearly refutes the prevailing interpretation that the large scaling exponent gamma is a result of highly extended backbone conformations. PMID- 26544637 TI - Association of TNF-alpha gene variations with thoracic aortic dissection risk in a Chinese Han population. AB - BACKGROUND: Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-alpha were associated with TAD. METHODS: Frequency distributions of TNF-alpha promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and -238G/A) were determined by direct sequencing. TNF-alpha plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-alpha mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification. RESULTS: We found the TNF-alpha promoter -857C/T polymorphism is associated with disease progression susceptibility in TAD patients. The CC homozygote of TAD patients had a significantly higher risk of TAD than did T allele carriers (P< 0.05). Plasma TNF-alpha concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-alpha levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF alpha mRNA levels compared with cells carrying the T allele. CONCLUSIONS: The 857C/T polymorphism of TNF-alpha promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-alpha expression in TAD patients, and may be an independent predictive factor for TAD. PMID- 26544638 TI - Association of Arsenic and Phosphorus with Iron Nanoparticles between Streams and Aquifers: Implications for Arsenic Mobility. AB - The microbial oxidation of organic matter coupled to reductive iron oxide dissolution is widely recognized as the dominant mechanism driving elevated arsenic (As) concentrations in aquifers. This paper considers the potential of nanoparticles to increase the mobility of As in aquifers, thereby accounting for discrepancies between predicted and observed As transport reported elsewhere. Arsenic, phosphorus, and iron size distributions and natural organic matter association were examined along a flow path from surface water via the hyporheic zone to shallow groundwater. Our analysis demonstrates that the colloidal Fe concentration (>1 kDa) correlates with both colloidal P and colloidal As concentrations. Importantly, increases in the concentration of colloidal P (>1 kDa) were positively correlated with increases in the concentration of nominally dissolved As (<1 kDa), but no correlation was observed between colloidal As and nominally dissolved P. This suggests that P actively competes for adsorption sites on Fe nanoparticles, displacing adsorbed As, thus mirroring their interaction with Fe oxides in the aquifer matrix. Dynamic redox fronts at the interface between streams and aquifers may therefore provide globally widespread conditions for the generation of Fe nanoparticles, a mobile phase for As adsorption currently not a part of reactive transport models. PMID- 26544639 TI - L-Amino Acid Based Urea-Tertiary Amine-Catalyzed Chemoselective and Asymmetric Stereoablative Carboxylation of 3-Bromooxindoles with Malonic Acid Half Thioesters. AB - An L-amino acid based urea-tertiary amine-catalyzed enantioselective stereoablative carboxylation of 3-bromooxindoles with malonic acid half thioesters (MAHTs) and diverse commercially available carboxylic acids has been developed. A series of valuable 3-substituted 3-hydroxy-2-oxindoles were obtained in high enantioselectivities (up to 93% ee). This chemoselective reaction represents the first example of MAHTs as carboxylating agents. PMID- 26544641 TI - Role of Organic Coatings in Regulating N2O5 Reactive Uptake to Sea Spray Aerosol. AB - Previous laboratory measurements and field observations have suggested that the reactive uptake of N2O5 to sea spray aerosol particles is a complex function of particle chemical composition and phase, where surface active organics can suppress the reactive uptake by up to a factor of 60. To date, there are no direct studies of the reactive uptake of N2O5 to nascent sea spray aerosol that permit assessment of the role that organic molecules present in sea spray aerosol (SSA) may play in suppressing or enhancing N2O5 uptake kinetics. In this study, SSA was generated from ambient seawater and artificial seawater matrices using a Marine Aerosol Reference Tank (MART), capable of producing nascent SSA representative of ambient conditions. The reactive uptake coefficient of N2O5 (gamma(N2O5)) on nascent SSA was determined using an entrained aerosol flow reactor coupled to a chemical ionization mass spectrometer for measurement of surface area dependent heterogeneous loss rates. Population averaged measurements of gamma(N2O5) for SSA generated from salt water sequentially doped with representative organic molecular mimics, or from ambient seawater, do not deviate statistically from that observed for sodium chloride (gamma(N2O5)NaCl = 0.01 0.03) for relative humidity (RH) ranging between 50 and 65%. The results are consistent with measurements made under clean marine conditions at the Scripps Institution of Oceanography Pier and those conducted on nascent SSA generated in the marine aerosol reference tank. The results presented here suggest that organic films present on nascent SSA (at RH greater than 50%) likely do not significantly limit N2O5 reactive uptake. PMID- 26544640 TI - Quantitative Proteomic Approaches for Analysis of Protein S-Nitrosylation. AB - S-Nitrosylation is a redox-based post-translational modification of a protein in response to nitric oxide (NO) signaling, and it participates in a variety of processes in diverse biological systems. The significance of this type of protein modification in health and diseases is increasingly recognized. In the central nervous system, aberrant S-nitrosylation, due to excessive NO production, is known to cause protein misfolding, mitochondrial dysfunction, transcriptional dysregulation, and neuronal death. This leads to an altered physiological state and consequently contributes to pathogenesis of neurodegenerative disorders. To date, much effort has been made to understand the mechanisms underlying protein S nitrosylation, and several approaches have been developed to unveil S nitrosylated proteins from different organisms. Interest in determining the dynamic changes of protein S-nitrosylation under different physiological and pathophysiological conditions has underscored the need for the development of quantitative proteomic approaches. Currently, both gel-based and gel-free mass spectrometry-based quantitative methods are widely used, and they each have advantages and disadvantages but may also be used together to produce complementary data. This review evaluates current available quantitative proteomic techniques for the analysis of protein S-nitrosylation and highlights recent advances, with emphasis on applications in neurodegenerative diseases. An important goal is to provide a comprehensive guide of feasible quantitative proteomic methodologies for examining protein S-nitrosylation in research to yield insights into disease mechanisms, diagnostic biomarkers, and drug discovery. PMID- 26544642 TI - Generating Health Estimates by Zip Code: A Semiparametric Small Area Estimation Approach Using the California Health Interview Survey. AB - OBJECTIVES: We propose a method to meet challenges in generating health estimates for granular geographic areas in which the survey sample size is extremely small. METHODS: Our generalized linear mixed model predicts health outcomes using both individual-level and neighborhood-level predictors. The model's feature of nonparametric smoothing function on neighborhood-level variables better captures the association between neighborhood environment and the outcome. Using 2011 to 2012 data from the California Health Interview Survey, we demonstrate an empirical application of this method to estimate the fraction of residents without health insurance for Zip Code Tabulation Areas (ZCTAs). RESULTS: Our method generated stable estimates of uninsurance for 1519 of 1765 ZCTAs (86%) in California. For some areas with great socioeconomic diversity across adjacent neighborhoods, such as Los Angeles County, the modeled uninsured estimates revealed much heterogeneity among geographically adjacent ZCTAs. CONCLUSIONS: The proposed method can increase the value of health surveys by providing modeled estimates for health data at a granular geographic level. It can account for variations in health outcomes at the neighborhood level as a result of both socioeconomic characteristics and geographic locations. PMID- 26544648 TI - Columbia Public Health Core Curriculum: Short-Term Impact. AB - We evaluated a transformed core curriculum for the Columbia University, Mailman School of Public Health (New York, New York) master of public health (MPH) degree. The curriculum, launched in 2012, aims to teach public health as it is practiced: in interdisciplinary teams, drawing on expertise from multiple domains to address complex health challenges. We collected evaluation data starting when the first class of students entered the program and ending with their graduation in May 2014. Students reported being very satisfied with and challenged by the rigorous curriculum and felt prepared to integrate concepts across varied domains and disciplines to solve public health problems. This novel interdisciplinary program could serve as a prototype for other schools that wish to reinvigorate MPH training. PMID- 26544649 TI - Ligand-Mediated "Turn On," High Quantum Yield Near-Infrared Emission in Small Gold Nanoparticles. AB - Small gold nanoparticles (~1.4-2.2 nm core diameters) exist at an exciting interface between molecular and metallic electronic structures. These particles have the potential to elucidate fundamental physical principles driving nanoscale phenomena and to be useful in a wide range of applications. Here, we study the optoelectronic properties of aqueous, phosphine-terminated gold nanoparticles (core diameter = 1.7 +/- 0.4 nm) after ligand exchange with a variety of sulfur containing molecules. No emission is observed from these particles prior to ligand exchange, however the introduction of sulfur-containing ligands initiates photoluminescence. Further, small changes in sulfur substituents produce significant changes in nanoparticle photoluminescence features including quantum yield, which ranges from 0.13 to 3.65% depending on substituent. Interestingly, smaller ligands produce the most intense, highest energy, narrowest, and longest lived emissions. Radiative lifetime measurements for these gold nanoparticle conjugates range from 59 to 2590 MUs, indicating that even minor changes to the ligand substituent fundamentally alter the electronic properties of the luminophore itself. These results isolate the critical role of surface chemistry in the photoluminescence of small metal nanoparticles and largely rule out other mechanisms such as discrete (Au(I)-S-R)n impurities, differences in ligand densities, and/or core diameters. Taken together, these experiments provide important mechanistic insight into the relationship between gold nanoparticle near-infrared emission and pendant ligand architectures, as well as demonstrate the pivotal role of metal nanoparticle surface chemistry in tuning and optimizing emergent optoelectronic features from these nanostructures. PMID- 26544650 TI - Highly Flexible Full Lithium Batteries with Self-Knitted alpha-MnO2 Fabric Foam. AB - Flexible/bendable electronic equipment has attracted great interest recently, while the development is hindered by fabricating flexible/bendable power sources due to the lack of reliable materials that combine both electronically superior conductivity and mechanical flexibility. Here, a novel structure of manganese oxide, like fabric foam, was constructed, which was then cocooned with a carbon shell via chemical vapor deposition. Serving as a binder-free anode, the self knitted MnO2@Carbon Foam (MCF) exhibits high specific capacitance (850-950 mAh/g), excellent cycling stability (1000 cycles), and good rate capability (60 C, 1 C = 1 A/g). Moreover, a flexible full lithium battery was designed based on an MCF anode and a LiCoO2/Al cathode, and the outstanding performance (energy density of 2451 Wh/kg at a power density of 4085 W/kg) demonstrates its promising potential of the practical applications. PMID- 26544651 TI - Oral vs Transdermal Estrogen Therapy and Vascular Events: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Menopausal hormone therapy is widely used to alleviate climacteric symptoms but may increase the risk of venous and arterial vascular events. OBJECTIVE: The objective was to synthesize the evidence about the risk of vascular events in postmenopausal women who use oral estrogen therapy (ET) and transdermal ET. METHODS: We searched bibliographical databases through August 2013 for longitudinal comparative studies that enrolled postmenopausal women using either oral or transdermal ET and reported the outcomes of interest: venous thromboembolism (VTE), pulmonary embolism, deep venous thrombosis (DVT), myocardial infarction (MI), and stroke. Two reviewers independently selected and appraised studies. Outcomes were pooled using random effects meta-analysis and were reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 15 observational studies at moderate risk of bias with follow-up of 3 to 20.25 years. When compared to transdermal ET, oral ET was associated with increased risk of a first episode of VTE (RR, 1.63; 95% CI, 1.40-1.90; I(2) = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I(2) = 0 %), and possibly stroke (RR, 1.24; 95% CI, 1.03-1.48; a single case-controlled study), but not MI (RR, 1.17; 95% CI, 0.80-1.71; I(2) = 74%). CONCLUSION: Observational evidence warranting low confidence suggests that compared to transdermal ET, oral ET may be associated with increased risk of VTE and DVT, but not MI. PMID- 26544652 TI - Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: The objective was to assess the effect of menopausal hormonal therapy (MHT) on all-cause and cause-specific mortality. METHODS: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus) from inception until August 2013. We included randomized controlled trials (RCTs) of more than 6 months of duration comparing MHT with no treatment. Pairs of independent reviewers selected trials, assessed risk of bias and extracted data. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using the random-effects model. RESULTS: We included 43 RCTs at moderate risk of bias. Meta analysis showed no effect on mortality (RR 0.99 [95% CI, 0.94-1.05]), regardless of MHT type or history of preexisting heart disease. No association was found between MHT and cardiac death (RR 1.04 [95% CI 0.87-1.23]) or stroke (RR 1.49 [95% CI 0.95-2.31]). Estrogen plus progesterone use was associated with a likely increase in breast cancer mortality (RR 1.96 [95% CI 0.98-3.94]), whereas estrogen use was not. MHT use was not associated with mortality of other types of cancer. In 5 trials, MHT was likely started at a younger age: 2 RCTs with mean age less than 60 and 3 RCTs with MHT started less than 10 years after menopause. Meta-analysis of these 5 RCTs showed a reduction of mortality with MHT (RR 0.70 [95% CI 0.52-0.95]). CONCLUSION: The current evidence suggests that MHT does not affect the risk of death from all causes, cardiac death and death from stroke or cancer. These data may be used to support clinical and policy deliberations about the role of MHT in the care of symptomatic postmenopausal women. PMID- 26544655 TI - Letter to the Editor: DDT Exposure In Utero and Breast Cancer. PMID- 26544656 TI - Response to the Letter by Paumgartten F. PMID- 26544657 TI - Letter to the Editor: Comment on "Effect of Growth Hormone Treatment on Fractures and Quality of Life in Postmenopausal Osteoporosis: A 10-Year Follow-Up Study" by Kratz E., et al. PMID- 26544658 TI - Response to the Letter by Salvatori R. PMID- 26544659 TI - Letter to the Editor: The Underestimated Role of the Lipid-Bound Character of Vitamin D Binding Protein. PMID- 26544660 TI - Response to Letter by Speeckaert M., et al. PMID- 26544661 TI - Letter to the Editor: Progress of Diabetic Severity and Risk of Dementia by Chiu P.C., et al. PMID- 26544662 TI - Response to the Letter by Sacerdote A., et al. PMID- 26544663 TI - Letter to the Editor: Comment on "The Impact of Chronic Liraglutide Therapy on Glucagon Secretion in Type 2 Diabetes: Insight From the LIBRA Trial" by Kramer C.K., et al. PMID- 26544664 TI - Response to the Letter by Kalra S. et al. PMID- 26544665 TI - Letter to the Editor: Epidemiologic Association Between Antibiotic Use With the Risk of Developing Type 2 Diabetes Mellitus. PMID- 26544666 TI - Response to the Letter: "Epidemiologic Association Between Antibiotic Use With the Risk of Developing Type 2 Diabetes" by Lopez-Hernandez, D. PMID- 26544667 TI - Development of a Virtual Approach-Avoidance Task to Assess Alcohol Cravings. AB - The aim of the present study was to develop a new approach-avoidance task in a virtual environment that could be used to assess the response to virtual alcohol related situations by heavy social drinkers (HSDs) and light social drinkers (LSDs). Thirty-six male undergraduates (18 HSDs, 18 LSDs) responded to signals when they pulled or pushed a joystick after watching scenes of alcohol- or nonalcohol-related situations in a virtual environment. The HSD group spent more time on moving away from alcohol-related situations than nonalcohol-related situations. We found that the HSD group had difficulty in avoiding alcohol related situations in the virtual environment. The Virtual Approach-Avoidance Task might more accurately measure the levels of social drinkers' craving to drink as it provides realistic situations and allows individuals to be immersed in virtual environments. PMID- 26544668 TI - Emotional and Nonemotional Conflict Processing in Pediatric and Adult Anxiety Disorders. AB - OBJECTIVE: Perturbations in emotional conflict adaptation, an implicit regulatory process, have been observed in adult anxiety disorders. However, findings remain inconsistent and restricted to adults. The current study compares conflict adaptation in youth and adults, with and without anxiety disorders. We predicted conflict adaptation would be present in the healthy but not the anxious groups. METHODS: In a clinic setting, 111 participants (27 healthy youth, 22 anxious youth, 41 healthy adults, and 21 anxious adults) completed emotional and nonemotional conflict tasks. Groups did not differ (all p's >0.1) on intelligence quotient (IQ), gender, and socioeconomic status; age did not differ between healthy and anxious subjects in either age cohort. Separate four way mixed-design analyses of variance were conducted to test hypotheses regarding the influence of diagnosis, age group, and task type on accuracy (percent correct) and reaction time (RT) for conflict adaptation (incongruent trials preceded by incongruent vs. congruent trials) and conflict detection (incongruent vs. congruent trials). RESULTS: Measures of conflict adaptation did not interact with diagnosis or age. There was a significant main effect of conflict adaptation across the overall sample in the expected direction for accuracy, but not RT. The well-replicated conflict detection effect also did emerge across tasks, with slower RT and lower accuracy for incongruent than for congruent trials. These effects were greater for the emotional than for nonemotional tasks. Finally, there were age differences in accuracy-based conflict detection specific to the emotional task, for which the size of the effect was larger for youth than for adults. CONCLUSIONS: The current study of youth and adults did not replicate prior behavioral findings of failure to engage conflict adaptation in anxiety disorders. Therefore, more work is needed before widely adopting conflict adaptation paradigms as a standard neurocognitive marker for anxiety disorders. PMID- 26544669 TI - Loss of Mismatched HLA on the Leukemic Blasts of Patients With Relapsed Lymphoid Malignancies Following Bone Marrow Transplantation From Related Donors With HLA Class II Mismatches in the Graft Versus Host Direction. AB - Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors. PMID- 26544670 TI - Holographic analysis on deformation and restoration of malaria-infected red blood cells by antimalarial drug. AB - Malaria parasites induce morphological, biochemical, and mechanical changes in red blood cells (RBCs). Mechanical variations are closely related to the deformability of individual RBCs. The deformation of various RBCs, including healthy and malaria-infected RBCs (iRBCs), can be directly observed through quantitative phase imaging (QPI). The effects of chloroquine treatment on the mechanical property variation of iRBCs were investigated using time-resolved holographic QPI of single live cells on a millisecond time scale. The deformabilities of healthy RBCs, iRBCs, and drug-treated iRBCs were compared, and the effect of chloroquine on iRBC restoration was experimentally examined. The present results are beneficial to elucidate the dynamic characteristics of iRBCs and the effect of the antimalarial drug on iRBCs. PMID- 26544671 TI - Causes of non-malarial febrile illness in outpatients in Tanzania. AB - OBJECTIVE: In sub-Saharan Africa, the use of malaria rapid diagnostic tests (mRDT) has raised awareness of alternative fever causes in children but few studies have included adults. To address this gap, we conducted a study of mRDT negative fever aetiologies among children and adults in Tanzania. METHODS: A total of 1028 patients aged 3 months to 50 years with a febrile illness and negative mRDT were enrolled from a Tanzanian hospital outpatient department. All had a physical examination and cultures from blood, nasopharynx/throat and urine. Patients were followed on Days 7 and 14 and children meeting WHO criteria for pneumonia were followed on Day 2 with chest radiology. RESULTS: Respiratory symptoms were the most frequent presenting complaint, reported by 20.3% of adults and 64.0% (339/530) of children. Of 38 X-rayed children meeting WHO pneumonia criteria, 47.4% had a normal X-ray. Overall, only 1.3% of 1028 blood cultures were positive. Salmonella typhi was the most prevalent pathogen isolated (7/13, 53.8%) and S. typhi patients reported fever for a median of 7 days (range 2-14). Children with bacteraemia did not present with WHO symptoms requiring antibiotic treatment. Young children and adults had similar prevalences of positive urine cultures (24/428 and 29/498, respectively). CONCLUSION: Few outpatient fevers are caused by blood stream bacterial infection, and most adult bacteraemia would be identified by current clinical guidelines although paediatric bacteraemia may be more difficult to diagnose. While pneumonia may be overdiagnosed, urinary tract infection was relatively common. Our results emphasise the difficulty in identifying African children in need of antibiotics among the majority who do not. PMID- 26544672 TI - Exercise training to improve exercise capacity and quality of life in people with non-malignant dust-related respiratory diseases. AB - BACKGROUND: Non-malignant dust-related respiratory diseases, such as asbestosis and silicosis, are similar to other chronic respiratory diseases and may be characterised by breathlessness, reduced exercise capacity and reduced health related quality of life. Some non-malignant dust-related respiratory diseases are a global health issue and very few treatment options, including pharmacological, are available. Therefore, examining the role of exercise training is particularly important to determine whether exercise training is an effective treatment option in non-malignant dust-related respiratory diseases. OBJECTIVES: To assess the effects of exercise training for people with non-malignant dust-related respiratory diseases compared with control, placebo or another non-exercise intervention on exercise capacity, health-related quality of life and levels of physical activity. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, EMBASE, CINAHL, PEDro and AMED (all searched from inception until February 2015), national and international clinical trial registries, reference lists of relevant papers and we contacted experts in the field for identification of suitable studies. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that compared exercise training of at least four weeks duration with no exercise training, placebo or another non exercise intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed study eligibility and risk of bias, and extracted data. We employed the GRADE approach to assess the overall quality of evidence for each outcome and to interpret findings. We synthesized study results using a random-effects model based on the assessment of heterogeneity. We conducted subgroup analyses on participants with dust-related interstitial lung diseases (ILDs) and participants with asbestos related pleural disease (ARPD). MAIN RESULTS: Two RCTs including a combined total of 40 participants (35 from one study and five from a second study) met the inclusion criteria. Twenty-one participants were randomised to the exercise training group and 19 participants were randomised to the control group. The included studies evaluated the effects of exercise training compared to a control group of no exercise training in people with dust-related ILDs and ARPD. The exercise training programme in both studies was in an outpatient setting for an eight-week period. The risk of bias was low in both studies. There were no reported adverse events of exercise training. Following exercise training, six minute walk distance (6MWD) increased with a mean difference (MD) of 53.81 metres (m) (95% CI 34.36 to 73.26 m). Improvements were also seen in the domains of health-related quality of life: Chronic Respiratory Disease Questionnaire (CRQ) Dyspnoea domain (MD 2.58, 95% CI 0.72 to 4.44); CRQ Fatigue domain (MD 1.00, 95% CI 0.11 to 1.89); CRQ Emotional Function domain (MD 2.61, 95% CI 0.74 to 4.49); and CRQ Mastery domain (MD 1.51, 95% CI 0.29 to 2.72). Improvements in exercise capacity and health-related quality of life were also evident six months following the intervention period: 6MWD (MD 52.68 m, 95% CI 27.43 to 77.93 m); CRQ Dyspnoea domain (MD 3.03, 95% CI 1.41 to 4.66); CRQ Emotional Function domain (MD 5.57, 95% CI 2.34 to 8.81); and CRQ Mastery domain (MD 2.66, 95% CI 1.08 to 4.23). Exercise training did not result in improvements in the Modified Medical Research Council (MMRC) dyspnoea scale immediately following exercise training or six months following exercise training. The improvements following exercise training were similar in a subgroup of participants with dust-related ILDs and in a subgroup of participants with ARPD compared to the control group, with no statistically significant differences in treatment effects between the subgroups. AUTHORS' CONCLUSIONS: The evidence examining exercise training in people with non malignant dust-related respiratory diseases is of very low quality. This is due to imprecision in the results from the small number of trials and the small number of participants, the indirectness of evidence due to a paucity of information on disease severity and the data from one study being from a subgroup of participants, and inconsistency from high heterogeneity in some results. Therefore, although the review findings indicate that an exercise training programme is effective in improving exercise capacity and health-related quality of life in the short-term and at six months follow-up, we remain unsure of these findings due to the very low quality evidence. Larger, high quality trials are needed to determine the strength of these findings. PMID- 26544673 TI - Specification of anteroposterior axis by combinatorial signaling during Xenopus development. AB - The specification of anteroposterior (AP) axis is a fundamental and complex patterning process that sets up the embryonic polarity and shapes a multicellular organism. This process involves the integration of distinct signaling pathways to coordinate temporal-spatial gene expression and morphogenetic movements. In the frog Xenopus, extensive embryological and molecular studies have provided major advance in understanding the mechanism implicated in AP patterning. Following fertilization, cortical rotation leads to the transport of maternal determinants to the dorsal region and creates the primary dorsoventral (DV) asymmetry. The activation of maternal Wnt/beta-catenin signaling and a high Nodal signal induces the formation of the Nieuwkoop center in the dorsal-vegetal cells, which then triggers the formation of the Spemann organizer in the overlying dorsal marginal zone. It is now well established that the Spemann organizer plays a central role in building the vertebrate body axes because it provides patterning information for both DV and AP polarities. The antagonistic interactions between signals secreted in the Spemann organizer and the opposite ventral region pattern the mesoderm along the DV axis, and this DV information is translated into AP positional values during gastrulation. The formation of anterior neural tissue requires simultaneous inhibition of zygotic Wnt and bone morphogenetic protein (BMP) signals, while an endogenous gradient of Wnt, fibroblast growth factors (FGFs), retinoic acid (RA) signaling, and collinearly expressed Hox genes patterns the trunk and posterior regions. Collectively, DV asymmetry is mostly coupled to AP polarity, and cell-cell interactions mediated essentially by the same regulatory networks operate in DV and AP patterning. For further resources related to this article, please visit the WIREs website. PMID- 26544674 TI - Factors associated with dental caries in a group of American Indian children at age 36 months. AB - OBJECTIVES: Early childhood caries (ECC) is rampant among American Indian children, but there has been relatively little study of this problem. This article reports on risk factors for caries for a group of American Indian children at age 36 months as part of a longitudinal study. METHODS: Pregnant women from a Northern Plains Tribal community were recruited to participate in a longitudinal study of caries and caries risk factors. Standardized dental examinations were completed on children, and questionnaires were completed by mothers at baseline and when children were 4, 8, 12, 16, 22, 28, and 36 months of age. Examinations were surface-specific for dental caries, and the questionnaires collected data on demographic, dietary, and behavioral factors. Nonparametric bivariate tests and logistic regression models were used to identify risk factors for caries at 36 months, and negative binomial regression was used to identify factors related to caries severity (dmf counts). RESULTS: Among the 232 children, and caries prevalence for cavitated lesions was 80%, with an additional 15% having only noncavitated lesions. The mean dmfs was 9.6, and of the total dmfs, nearly 62% of affected surfaces were decayed, 31% were missing, and 7% were filled. Logistic regression identified higher added-sugar beverage consumption, younger maternal age at baseline, higher maternal DMFS at baseline, and greater number of people in the household as significant (P < 0.05) risk factors. Negative binomial regression found that only maternal DMFS was associated with child dmf counts. CONCLUSIONS: By the age of 36 months, dental caries is nearly universal in this population of American Indian children. Caries risk factors included sugared beverage consumption, greater household size, and maternal factors, but further analyses are needed to better understand caries in this population. PMID- 26544675 TI - Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane reviews. AB - BACKGROUND: Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. OBJECTIVES: To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain. METHODS: We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo. MAIN RESULTS: We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo. AUTHORS' CONCLUSIONS: There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview. PMID- 26544676 TI - Hemoglobin Variants in Northern Thailand: Prevalence, Heterogeneity and Molecular Characteristics. AB - BACKGROUND: There are limited data on hemoglobin (Hb) variants among peoples of northern Thailand. Hence, we determined the prevalence of Hb variants among a large cohort from this region. METHODS: A study was done on 23,914 subjects recruited from eight provinces during June 2012-January 2014. Hb was analyzed by high performance liquid chromatography (HPLC) and capillary electrophoresis, and corresponding mutations were identified by polymerase chain reaction. RESULTS: Among 23,914 subjects examined, 211 (0.88%) were found to carry 14 different Hb variants. Five alpha-globin chain variants were identified: Hb Q-Thailand (n = 40; 19.0%), Hb Hekinan (n = 8, 3.8%), Hb Siam (n = 2, 0.9%), Hb Beijing (n = 1, 0.5%), and Hb Kawachi (n = 1, 0.5%), not previously described in the Thai population. Seven beta-globin variants, including Hb Hope, Hb Tak, Hb S, Hb J Bangkok, Hb G-Makassar, Hb C, and Hb Korle-Bu, were found in 115 (54.5%), 30 (14.2%), 3 (1.4%), 3 (1.4%), 1 (0.5%), 1 (0.5%), and 1 (0.5%) subjects, respectively. The remaining five subjects (2.4%) were carriers of two different delta-globin chain variants. A different spectrum and frequencies of Hb variants were noted compared to other geographical areas. Haplotype analysis demonstrated multiple origins for Hbs Hope and Tak and confirmed a non-African origin of Hb C. Several genetic interactions between these variants with other hemoglobinopathies were encountered. Associated hematological phenotypes and novel Hb derivatives formed were presented. CONCLUSIONS: The prevalence and molecular heterogeneities of the Hb variants found in this large cohort of the northern Thai people's should prove useful in developing a screening program, and for the performance of additional population genetics studies of hemoglobinopathy in the region. PMID- 26544677 TI - Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with age of smoking initiation in male schizophrenia smokers. AB - Schizophrenia patients exhibit higher smoking rates than the general population. A growing body of evidence suggests that cigarette smoke impairs the antioxidant defense mechanisms, leading to oxidative damage. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalyzing the metabolism of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterized functional polymorphism, Ala-9Val of MnSOD, a number of studies have evaluated the association between Val-9Ala and schizophrenia or cancer. In this study, we hypothesized that the functional polymorphism of MnSOD Ala-9Val was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 666 chronic male schizophrenia patients (smoker/never-smoker = 507/159) and 660 male controls (smoker/never-smoker = 360/300) using a case-control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in MnSOD Ala-9Val genotype and allele distributions between the patients and healthy controls or between smokers and never-smokers in either patients or healthy controls alone. The smokers with the Ala allele started smoking significantly earlier (19.9 +/- 5.8 vs. 21.7 +/- 6.5 years, P = 0.005) only in patients. These results suggest that the MnSOD Ala-9Val polymorphism may not influence smoking status in a Chinese male schizophrenia population, but may influence the age at which smoking is started among schizophrenia smokers. PMID- 26544678 TI - Correction: Phase-amplitude coupling supports phase coding in human ECoG. PMID- 26544679 TI - The messy process of guiding proteins into membranes. PMID- 26544681 TI - Corneal Microstructural Changes in Nerve Fiber, Endothelial and Epithelial Density After Cataract Surgery in Patients With Diabetes Mellitus: Erratum. AB - In the article that appears in the February 2015 issue of Cornea, in the 6th paragraph of the Results, the P value of the difference in endothelial cell density (ECD) between the DM and non-DM groups should be 0.2 and not 0.02. The sentence should read as follows: There was no significant difference in preoperative ECD between the DM group (2254 +/- 426 cells/mm2) and non-DM group (2384 +/- 438 cells/mm2; P = 0.2). PMID- 26544680 TI - Protein aggregates are associated with replicative aging without compromising protein quality control. AB - Differentiation of cellular lineages is facilitated by asymmetric segregation of fate determinants between dividing cells. In budding yeast, various aging factors segregate to the aging (mother)-lineage, with poorly understood consequences. In this study, we show that yeast mother cells form a protein aggregate during early replicative aging that is maintained as a single, asymmetrically inherited deposit over the remaining lifespan. Surprisingly, deposit formation was not associated with stress or general decline in proteostasis. Rather, the deposit containing cells displayed enhanced degradation of cytosolic proteasome substrates and unimpaired clearance of stress-induced protein aggregates. Deposit formation was dependent on Hsp42, which collected non-random client proteins of the Hsp104/Hsp70-refolding machinery, including the prion Sup35. Importantly, loss of Hsp42 resulted in symmetric inheritance of its constituents and prolonged the lifespan of the mother cell. Together, these data suggest that protein aggregation is an early aging-associated differentiation event in yeast, having a two-faceted role in organismal fitness. PMID- 26544682 TI - Controlling Size, Morphology, and Surface Composition of AgAu Nanodendrites in 15 s for Improved Environmental Catalysis under Low Metal Loadings. AB - In this work, a simple but powerful method for controlling the size and surface morphology of AgAu nanodendrites is presented. Control of the number of Ag nanoparticle seeds is found to provide a fast and effective route by which to manipulate the size and morphology of nanoparticles produced via a combined galvanic replacement and reduction reaction. A lower number of Ag nanoparticle seeds leads to larger nanodendrites with the particles' outer diameter being tunable in the range of 45-148 nm. The size and surface morphology of the nanodendrites was found to directly affect their catalytic activity. Specifically, we report on the activity of these AgAu nanodendrites in catalyzing the gas-phase oxidation of benzene, toluene and o-xylene, which is an important reaction for the removal of these toxic compounds from fuels and for environmental remediation. All produced nanodendrite particles were found to be catalytically active, even at low temperatures and low metal loadings. Surprisingly, the largest nanodendrites provided the greatest percent conversion efficiencies. PMID- 26544683 TI - Expressions of miR-132, miR-134, and miR-485 in rat primary motor cortex during transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following brachial plexus avulsion injuries. AB - The transfer of a contralateral healthy seventh cervical spinal nerve root (cC7) to the recipient nerve in the injured side is considered a promising procedure for restoration of the physiological functions of an injured hand after brachial plexus root avulsion injury (BPAI). Growing evidence shows that transhemispheric cortical reorganization plays an important role in the functional recovery of the injured arm after cC7 nerve transfer surgery. However, the molecular mechanism underlying the transhemispheric cortical reorganization after cC7 transfer remains elusive. In the present study, we investigated the expression of miR-132, miR-134, and miR-485 in the rat primary motor cortex after cC7 transfer following BPAI by quantitative PCR. The results demonstrated the dynamic alteration in the expression of miR-132, miR-134, and miR-485 in the primary motor cortex of rats after cC7 transfer following BPAI. It indicates that microRNAs are involved in the dynamic transhemispheric functional reorganization after cC7 root transfer following BPAI. Together, this study is the first to provide evidence for the involvement of microRNAs during dynamic transhemispheric functional reorganization after cC7 transfer following BPAI. The results are useful for understanding the mechanism underlying transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following BPAI. PMID- 26544684 TI - Cardioprotective Effect of Phenytoin on Doxorubicin-induced Cardiac Toxicity in a Rat Model. AB - Doxorubicin (DOX) is an effective anticancer agent, but adverse cardiotoxic effects limit its use. Compounds reducing DOX cardiotoxicity could improve its therapeutic index. This study investigated the protective effects of phenytoin (Phen) for DOX-induced cardiomyopathy. Male Wistar rats were randomized into 5 groups to receive either saline, DOX (2 mg/kg per 48 hours, 6 doses, intraperitoneally) or DOX + Phen (5, 10, or 20 mg/kg/d, starting 4 days before DOX, intraperitoneally). The animals were assessed 24 hours after the last injection. Left ventricular (LV) function and hemodynamic parameters were assessed using transthoracic echocardiography, electrocardiography, and a Millar pressure catheter. Histopathological studies were performed, and the effect of Phen on the cytotoxicity of DOX was evaluated in vitro for the human breast adenocarcinoma cell line. DOX-impaired LV function significantly decreased the LV systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening, and contractility index. DOX caused structural changes in myocardial cells. Treatment with Phen decreased DOX-induced toxicity, significantly improved ventricular function, and ameliorated structural changes in the myocardium. Phen also did not interfere with the antitumor effect of DOX. The results confirm the cardioprotective effect of Phen against DOX-induced cardiomyopathy without removing antitumor effect of DOX. PMID- 26544685 TI - From Innovation to Diversification: A Simple Competitive Model. AB - Few attempts have been proposed in order to describe the statistical features and historical evolution of the export bipartite matrix countries/products. An important standpoint is the introduction of a products network, namely a hierarchical forest of products that models the formation and the evolution of commodities. In the present article, we propose a simple dynamical model where countries compete with each other to acquire the ability to produce and export new products. Countries will have two possibilities to expand their export: innovating, i.e. introducing new goods, namely new nodes in the product networks, or copying the productive process of others, i.e. occupying a node already present in the same network. In this way, the topology of the products network and the country-product matrix evolve simultaneously, driven by the countries push toward innovation. PMID- 26544687 TI - Levy Walks Suboptimal under Predation Risk. AB - A key challenge in movement ecology is to understand how animals move in nature. Previous studies have predicted that animals should perform a special class of random walks, called Levy walk, to obtain more targets. However, some empirical studies did not support this hypothesis, and the relationship between search strategy and ecological factors is still unclear. We focused on ecological factors, such as predation risk, and analyzed whether Levy walk may not be favored. It was remarkable that the ecological factors often altered an optimal search strategy from Levy walk to Brownian walk, depending on the speed of the predator's movement, density of predators, etc. This occurred because higher target encounter rates simultaneously led searchers to higher predation risks. Our findings indicate that animals may not perform Levy walks often, and we suggest that it is crucial to consider the ecological context for evaluating the search strategy performed by animals in the field. PMID- 26544686 TI - siRNA-Mediated Silencing of doublesex during Female Development of the Dengue Vector Mosquito Aedes aegypti. AB - The development of sex-specific traits, including the female-specific ability to bite humans and vector disease, is critical for vector mosquito reproduction and pathogen transmission. Doublesex (Dsx), a terminal transcription factor in the sex determination pathway, is known to regulate sex-specific gene expression during development of the dengue fever vector mosquito Aedes aegypti. Here, the effects of developmental siRNA-mediated dsx silencing were assessed in adult females. Targeting of dsx during A. aegypti development resulted in decreased female wing size, a correlate for body size, which is typically larger in females. siRNA-mediated targeting of dsx also resulted in decreased length of the adult female proboscis. Although dsx silencing did not impact female membrane blood feeding or mating behavior in the laboratory, decreased fecundity and fertility correlated with decreased ovary length, ovariole length, and ovariole number in dsx knockdown females. Dsx silencing also resulted in disruption of olfactory system development, as evidenced by reduced length of the female antenna and maxillary palp and the sensilla present on these structures, as well as disrupted odorant receptor expression. Female lifespan, a critical component of the ability of A. aegypti to transmit pathogens, was also significantly reduced in adult females following developmental targeting of dsx. The results of this investigation demonstrate that silencing of dsx during A. aegypti development disrupts multiple sex-specific morphological, physiological, and behavioral traits of adult females, a number of which are directly or indirectly linked to mosquito reproduction and pathogen transmission. Moreover, the olfactory phenotypes observed connect Dsx to development of the olfactory system, suggesting that A. aegypti will be an excellent system in which to further assess the developmental genetics of sex-specific chemosensation. PMID- 26544688 TI - Measuring Emotional Contagion in Social Media. AB - Social media are used as main discussion channels by millions of individuals every day. The content individuals produce in daily social-media-based micro communications, and the emotions therein expressed, may impact the emotional states of others. A recent experiment performed on Facebook hypothesized that emotions spread online, even in absence of non-verbal cues typical of in-person interactions, and that individuals are more likely to adopt positive or negative emotions if these are over-expressed in their social network. Experiments of this type, however, raise ethical concerns, as they require massive-scale content manipulation with unknown consequences for the individuals therein involved. Here, we study the dynamics of emotional contagion using a random sample of Twitter users, whose activity (and the stimuli they were exposed to) was observed during a week of September 2014. Rather than manipulating content, we devise a null model that discounts some confounding factors (including the effect of emotional contagion). We measure the emotional valence of content the users are exposed to before posting their own tweets. We determine that on average a negative post follows an over-exposure to 4.34% more negative content than baseline, while positive posts occur after an average over-exposure to 4.50% more positive contents. We highlight the presence of a linear relationship between the average emotional valence of the stimuli users are exposed to, and that of the responses they produce. We also identify two different classes of individuals: highly and scarcely susceptible to emotional contagion. Highly susceptible users are significantly less inclined to adopt negative emotions than the scarcely susceptible ones, but equally likely to adopt positive emotions. In general, the likelihood of adopting positive emotions is much greater than that of negative emotions. PMID- 26544689 TI - Developmental MYH3 Myopathy Associated with Expression of Mutant Protein and Reduced Expression Levels of Embryonic MyHC. AB - OBJECTIVE: An essential role for embryonic MyHC in foetal development has been found from its association with distal arthrogryposis syndromes, a heterogeneous group of disorders characterised by congenital contractions. The latter probably result from severe myopathy during foetal development. Lack of embryonic muscle biopsy material and suitable animal models has hindered study of the pathomechanisms linking mutations in MYH3 to prenatal myopathy. METHODS AND RESULTS: We determined the pathomechanisms of developmental myopathy caused by recurrent p.Thr178Ile MYH3 heterozygosity, using patient-derived skeletal muscle cells in culture as an experimental disease model to emulate early embryonic development. These cultured cells were processed for discrimination and quantitative analysis of mutant and wild-type MYH3 alleles and MyHC transcripts, real-time RT-qPCR, sequence analysis, immunofluorescence microscopy, immunoblot, and proteomic assessments. Involvement of the ubiquitin proteasome system was investigated in patients with p.Thr178Ile mutations in MYH3 and MYH2. We found equal overall expression of mutant and wild-type MyHC mRNAs and proteins. Compared to the controls, however, expression of embryonic MyHC transcripts and proteins was reduced whereas expression of myosin-specific E3 ubiquitin ligase (MuRF1) was increased. We also found delayed myofibrillogenesis and atrophic myotubes but structured sarcomeres. CONCLUSION: In conclusion, this study suggests that developmental p.Thr178Ile MYH3 myopathy is associated with a combined pathomechanism of insufficient dosage of functional embryonic MyHC and production of mutant protein. PMID- 26544690 TI - Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model. AB - Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT and Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting. PMID- 26544691 TI - Recursive Random Lasso (RRLasso) for Identifying Anti-Cancer Drug Targets. AB - Uncovering driver genes is crucial for understanding heterogeneity in cancer. L1 type regularization approaches have been widely used for uncovering cancer driver genes based on genome-scale data. Although the existing methods have been widely applied in the field of bioinformatics, they possess several drawbacks: subset size limitations, erroneous estimation results, multicollinearity, and heavy time consumption. We introduce a novel statistical strategy, called a Recursive Random Lasso (RRLasso), for high dimensional genomic data analysis and investigation of driver genes. For time-effective analysis, we consider a recursive bootstrap procedure in line with the random lasso. Furthermore, we introduce a parametric statistical test for driver gene selection based on bootstrap regression modeling results. The proposed RRLasso is not only rapid but performs well for high dimensional genomic data analysis. Monte Carlo simulations and analysis of the "Sanger Genomics of Drug Sensitivity in Cancer dataset from the Cancer Genome Project" show that the proposed RRLasso is an effective tool for high dimensional genomic data analysis. The proposed methods provide reliable and biologically relevant results for cancer driver gene selection. PMID- 26544692 TI - Butterfly Eyespots: Their Potential Influence on Aesthetic Preferences and Conservation Attitudes. AB - Research has shown that the mere presence of stimuli that resemble eyes is sufficient to attract attention, elicit aesthetic responses, and can even enhance prosocial behavior. However, it is less clear whether eye-like stimuli could also be used as a tool for nature conservation. Several animal species, including butterflies, develop eye-like markings that are known as eyespots. In the present research, we explored whether the mere display of eyespots on butterfly wings can enhance: (a) liking for a butterfly species, and (b) attitudes and behaviors towards conservation of a butterfly species. Four online experimental studies, involving 613 participants, demonstrated that eyespots significantly increased liking for a butterfly species. Furthermore, eyespots significantly increased positive attitudes towards conservation of a butterfly species (Studies 1, 2 and 4), whereas liking mediated the eyespot effect on conservation attitudes (Study 2). However, we also found some mixed evidence for an association between eyespots and actual conservation behavior (Studies 3 and 4). Overall, these findings suggest that eyespots may increase liking for an animal and sensitize humans to conservation. We discuss possible implications for biodiversity conservation and future research directions. PMID- 26544693 TI - Mechanical Coupling between Endoderm Invagination and Axis Extension in Drosophila. AB - How genetic programs generate cell-intrinsic forces to shape embryos is actively studied, but less so how tissue-scale physical forces impact morphogenesis. Here we address the role of the latter during axis extension, using Drosophila germband extension (GBE) as a model. We found previously that cells elongate in the anteroposterior (AP) axis in the extending germband, suggesting that an extrinsic tensile force contributed to body axis extension. Here we further characterized the AP cell elongation patterns during GBE, by tracking cells and quantifying their apical cell deformation over time. AP cell elongation forms a gradient culminating at the posterior of the embryo, consistent with an AP oriented tensile force propagating from there. To identify the morphogenetic movements that could be the source of this extrinsic force, we mapped gastrulation movements temporally using light sheet microscopy to image whole Drosophila embryos. We found that both mesoderm and endoderm invaginations are synchronous with the onset of GBE. The AP cell elongation gradient remains when mesoderm invagination is blocked but is abolished in the absence of endoderm invagination. This suggested that endoderm invagination is the source of the tensile force. We next looked for evidence of this force in a simplified system without polarized cell intercalation, in acellular embryos. Using Particle Image Velocimetry, we identify posteriorwards Myosin II flows towards the presumptive posterior endoderm, which still undergoes apical constriction in acellular embryos as in wildtype. We probed this posterior region using laser ablation and showed that tension is increased in the AP orientation, compared to dorsoventral orientation or to either orientations more anteriorly in the embryo. We propose that apical constriction leading to endoderm invagination is the source of the extrinsic force contributing to germband extension. This highlights the importance of physical interactions between tissues during morphogenesis. PMID- 26544694 TI - Learning Upright Standing on a Multiaxial Balance Board. AB - Upright stance on a balance board is a skill requiring complex rearrangement of the postural control. Despite the large use of these boards in training the standing posture, a comprehensive analysis of the learning process underlying the control of these devices is lacking. In this paper learning to maintain a stable stance on a multiaxial oscillating board was studied by analyzing performance changes over short and long periods. Healthy participants were asked to keep the board orientation as horizontal as possible for 20 sec, performing two sessions of 8 trials separated by 15-min pause. Memory consolidation was tested one week later. Amplitude and variability of the oscillations around horizontal plane and area and sway path of the board displacement decreased rapidly over the first session. The performance was stable during the second session, and retained after 1 week. A similar behavior was observed in the anterior-posterior and medial lateral directions for amplitude and variability parameters, with less stable balance in the anterior-posterior direction. Approximate entropy and mean power frequency, assessing temporal dynamics and frequency content of oscillations, changed only in the anterior-posterior direction during the retention test. Overall, the ability to stand on a balance board is rapidly acquired, and retained for long time. The asymmetric stability between anterior-posterior and medial-lateral directions replicates a structure observed in other standing stances, suggesting a possible transfer from previous postural experiences. Conversely, changes in the temporal dynamics and the frequency content could be associated with new postural strategies developed later during memory consolidation. PMID- 26544695 TI - p21WAF1 Is Required for Interleukin-16-Induced Migration and Invasion of Vascular Smooth Muscle Cells via the p38MAPK/Sp-1/MMP-9 Pathway. AB - Interleukin-16 (IL-16) is a lymphocyte chemoattractant factor well known for its role in immune responses, but its role in vascular disease is unknown. Here, we explored the novel physiological function of IL-16 in vascular smooth muscle cells (VSMCs). The expression of IL-16 and its receptor CD4 was observed in VSMCs. Treatment with IL-16 enhanced the migration and invasion by VSMCs without altering the proliferative potential. IL-16 induced MMP-9 expression via the binding activity of transcription factors NF-kappaB, AP-1, and Sp-1 motifs in VSMCs. Among the relevant signaling pathways examined, only p38MAPK phosphorylation was significantly stimulated in IL-16-treated VSMCs. Treatment with p38MAPK inhibitor SB203580 prevented the IL-16-induced migration and invasion of VSMCs. SB203580 treatment inhibited the MMP-9 expression and activation of Sp-1 binding in IL-16-treated VSMCs, and siRNA knockdown of CD4 expression blocked the induction of migration, invasion, p38MAPK phosphorylation, MMP-9 expression, and Sp-1 binding activation stimulated by IL-16. The IL-16 induced cell-cycle-inhibitor p21WAF1 expression in VSMCs, but had no effect on the expression levels of other cell-cycle negative regulators. Finally, blockage of p21WAF1 function with specific siRNA abolished the IL-16-induced elevation of migration, invasion, p38MAPK phosphorylation, MMP-9 expression, and Sp-1 binding activation in VSMCs. Taken together, p21WAF1 was required for the induction of p38MAPK-mediated MMP-9 expression via activation of the Sp-1 binding motif, which led to migration and invasion of VSMCs interacting with IL-16/CD4. These results could provide that IL-16 is a new target in the treatment of vascular diseases such as atherosclerosis and re-stenosis. PMID- 26544696 TI - Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus Associated Nephropathy after Renal Transplantation. AB - BACKGROUND: Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. METHODS: Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1-4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. RESULTS: After 32.1+/-26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25-34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. CONCLUSIONS: The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN. PMID- 26544697 TI - Twenty years of boosting antiretroviral agents: where are we today? PMID- 26544698 TI - Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts. AB - BACKGROUND: HIV elite controllers suppress HIV viremia without antiretroviral therapy (ART), yet previous studies demonstrated that elite controllers maintain an activated T-cell phenotype. Chronic immune activation has detrimental consequences and thus ART has been advocated for all elite controllers. However, elite controllers are not a clinically homogenous group. Since CD4% is among the best predictors of AIDS-related events, in the current study, we assessed whether this marker can be used to stratify elite controllers needing ART. METHODS: Sixteen elite controllers were divided into two groups based on CD4% (EC > 40% and EC <=40%), and T-cell subsets were analyzed for markers of memory/differentiation (CD45RA, CCR7, CD28), activation (CD38/HLA-DR), immunosenescence (CD57), costimulation (CD73, CD28) and exhaustion (PD-1, CD160, Tim-3). Monocyte subsets (CD14, CD16) were also analyzed and sCD14 levels were quantified using ELISA. RESULTS: In the EC group, expression of activation, exhaustion, and immunosensescence markers on T cells were significantly reduced compared with the EC group and similar to the seronegative controls. The EC group expressed higher levels of costimulatory molecules CD28 and CD73 and had lower levels of monocyte activation (HLA-DR expression) with a reduced frequency of inflammatory monocyte (CD14 CD16) subset. Furthermore, the EC group maintained a stable CD4% during a median follow-up of 6 years. CONCLUSION: Elite controllers with preserved CD4T cells (EC) have normal T-cell and monocyte phenotypes and therefore may have limited benefit from ART. CD4% can be an important marker for evaluating future studies aimed at determining the need for ART in this group of individuals. PMID- 26544699 TI - Effect of antiretroviral treatment on the risk of tuberculosis during South Africa's programme expansion. AB - OBJECTIVE: The objective of this study is to estimate the effectiveness of antiretroviral treatment (ART) in preventing tuberculosis (TB) in HIV-infected people during the first 6 years of ART programme expansion. DESIGN: A cohort study comparing TB risk without ART and after ART initiation. SETTING: Public sector HIV programme of the Free State province, South Africa. PARTICIPANTS: Seventy-four thousand and seventy-four HIV-infected people enrolled from 2004 until 2010, of whom 43 898 received ART and 30 176 did not. INTERVENTION: Combination ART. MAIN OUTCOME MEASURES: Time to first TB diagnosis, adjusted for CD4 cell count, weight, age, sex, previous TB, district and year, with ART, CD4 cell count and weight as time-varying covariates and with death as a competing risk. RESULTS: Three thousand eight hundred and fifty-eight first TB episodes occurred during 78 202 person-years at risk with ART and 5669 episodes occurred during 62 801 person-years without ART [incidence rates 4.9 and 9.0 per 100 person-years, crude incidence rate ratio 0.55 (95% confidence interval 0.52 0.57)]. The adjusted subhazard ratio (SHR) of time to first TB episode after starting ART, compared with follow-up without ART, was 0.67 (0.64-0.70). Within CD4 cell count subgroups (<50, 50-199, 100-199, 200-349 and >350 cells/MUl), the respective SHRs were 0.64 (0.57-0.71), 0.63 (0.57-0.70), 0.66 (0.61-0.72), 0.67 (0.62-0.72), 0.72 (0.63-0.83) and 0.97 (0.60-1.59). Adjusted SHRs for ART decreased with each year of enrolment, from 0.90 (0.77-1.04) in 2004 to 0.54 (0.43-0.67) in 2010. CONCLUSION: ART was effective in preventing TB in HIV infected patients with CD4 cell counts below 350 cells/MUl, but less so than previously estimated. Effectiveness increased each year. PMID- 26544700 TI - The risk of viral rebound in the year after delivery in women remaining on antiretroviral therapy. AB - OBJECTIVE: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART). METHODS: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50 copies/ml or less at delivery in 2006-2011, who started life-long cART during pregnancy (n = 321) or conceived on cART (n = 618), were matched by age, duration on cART and time period, with at least one control (non postpartum). The cumulative probability of viral rebound (HIV-RNA >200 copies/ml) was assessed by Kaplan-Meier analysis; adjusted hazard ratios (aHRs) for the 0-3 and 3-12 months postdelivery (cases)/pseudo-delivery (controls) were calculated in Cox proportional hazards models. RESULTS: In postpartum women who conceived on cART, 5.9% [95% confidence interval (95% CI) 4.0-7.7] experienced viral rebound by 3 months, and 2.2% (1.4-3.0%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during the first 3 months [aHR 2.63 (1.58-4.39)] but not during the 3-12 months postdelivery/pseudo-delivery. In postpartum women who started cART during pregnancy, 27% (22-32%) experienced viral rebound by 3 months, and 3.0% (1.6-4.4%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during both postdelivery/pseudo-delivery periods [<3 months: aHR 6.63 (3.58-12.29); 3-12 months: aHR 4.05 (2.03-8.09)]. CONCLUSION: In women on suppressive cART, the risk of viral rebound is increased following delivery, especially in the first 3 months, which may be related to reduced adherence, indicating the need for additional adherence support for postpartum women. PMID- 26544701 TI - Transient elastography for the detection of hepatic fibrosis in HIV-monoinfected adults with elevated aminotransferases on antiretroviral therapy. AB - OBJECTIVE: Vibration-controlled transient elastography (VCTE) is increasingly used to assess liver fibrosis in viral hepatitis and fatty liver disease populations. Because the accuracy of VCTE in HIV-monoinfected populations has not been established, we evaluated its performance in assessing liver fibrosis in a cohort of HIV-monoinfected adults undergoing liver biopsy as part of a recently published clinical trial. METHODS: HIV-infected adults with elevated aminotransferase levels for at least 6 months while receiving antiretroviral therapy, and without chronic viral hepatitis or other known causes of liver disease, were prospectively evaluated by VCTE, other noninvasive markers of fibrosis, and percutaneous liver biopsy as part of a cross-sectional study examining liver pathology. RESULTS: Sixty-six patients were evaluated by VCTE and liver biopsy. The cohort was in the majority male (92%), with a median age of 50 years (range 17-68). Biopsy identified bridging fibrosis in 14 (21%) and nonalcoholic steatohepatitis in 38 (58%) participants. VCTE was unsuccessful or unreliable in seven participants (11%). In the 59 participants with reliable results, median liver stiffness measurement (LSM) was 5.9 kPa (range 3.3-29.2 kPa); 25 participants (42%) had a LSM above 7.1 kPa, a value consistent with increased liver stiffness in other populations. VCTE had good sensitivity and specificity with an area under the receiver-operating characteristic curve (AUROC) of 93% for detection of moderate fibrosis (Ishak F >= 2; 95% confidence interval 86-99%). CONCLUSIONS: In HIV-monoinfected adults with biopsy-proven liver disease, LSM by VCTE was the best noninvasive predictor of fibrosis. Our findings support the continued use of VCTE for fibrosis screening in HIV monoinfected patients with elevated aminotransferases. PMID- 26544702 TI - Effects of abacavir administration on structural and functional markers of platelet activation. AB - BACKGROUND: Current abacavir exposure has been reported to be associated with cardiovascular disease. Changes in platelet reactivity could plausibly explain the clinically observed pattern of association. OBJECTIVE: To determine if platelet reactivity changed following abacavir exposure and whether this effect was reversible on cessation of the drug. METHODS: In an open-label, interventional study abacavir, 600 mg daily, was added to a suppressive antiretroviral regimen in 20 adult HIV-positive men. Platelet function, estimated by the phosphorylated vasodilator-stimulated phosphoprotein (P-VASP) assay and through measurement of the expression and shedding of platelet-specific receptors, was assessed at baseline, following 15 days of abacavir and at completion of a 28-day washout period. RESULTS: The VASP-index decreased significantly from 79.1% [interquartile range (IQR) 47.8-87.6] to 32.6% (IQR 11.5-51.0) following 15 days of abacavir administration (P = 0.010), and returned to baseline levels following the washout period (day 43 =76.3%; IQR 40.7-92.3). There was no change in resting (prostaglandin E1 alone) P-VASP but a slight increase in P-VASP within stimulated platelets (prostaglandin E1 and adenosine diphosphate). Integrin beta3 levels decreased significantly [208.5 ng/ml (IQR 177.0-231.1) to 177.5 ng/ml (IQR 151.7-205) P < 0.001] and there was a nonsignificant trend towards decreased soluble glycoprotein VI levels [baseline; 72.5 ng/ml (95% CI 58.3-81.5) vs. day 15; 45.0 ng/ml (95% CI 33.0-98.2) P = 0.79]. CONCLUSION: Abacavir led to reversible changes in platelet function and structure. The clinical implications of these changes are uncertain; they may represent negative feedback mechanisms in response to an abacavir-associated prothrombotic state. PMID- 26544703 TI - Incidence of benign prostate hypertrophy in Danish men with and without HIV infection. AB - BACKGROUND: Information on risk of benign prostate hypertrophy (BPH) in HIV infected men is sparse. We aimed to estimate the incidence of being diagnosed with BPH among HIV-infected men compared with an age and sex-matched comparison cohort from the background population. To exclude that family-associated risk factors influence risk of BPH diagnoses in families of HIV-infected individuals, we estimated risk of BPH in fathers of HIV-infected men and fathers of the comparison cohort. METHODS: In a nationwide, population-based, matched cohort study, we calculated incidence rates and used Poisson regression models to calculate incidence rate ratios (IRRs) of being diagnosed with BPH, defined as the earliest of date of the second redeemed prescription of a drug used to treat BPH, the first registration of a BPH diagnosis in the Danish National Hospital Registry (DNHR) or the first registration of a surgical procedure for BPH in DNHR. RESULTS: We identified 4633 HIV-infected men, 46 330 comparison cohort individuals, 1585 fathers of HIV-infected men and 20 449 fathers of the comparison cohort. Incidence rate of being diagnosed with BPH was 37.0 [95% confidence interval (95% CI) 31.5-43.1] per 10 000 person-years of follow-up among HIV-infected men and was not increased compared with the comparison cohort (IRR 1.04, 95% CI 0.88-1.22). Risk was not increased for fathers of HIV-infected men vs. fathers of the comparison cohort (IRR 0.99, 95% CI 0.87-1.12). Stratified analyses did not change the above results markedly. CONCLUSION: HIV-infected individuals do not have an increased risk of being diagnosed with BPH. PMID- 26544704 TI - Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4+ T-cell recovery once HIV-1 suppression is achieved? AB - OBJECTIVE: This article compares trends in CD4 T-cell recovery and proportions achieving optimal restoration (>=500 cells/MUl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. METHODS: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4 less than 200 cells/MUl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. RESULTS: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4 T-cell count at cART start (baseline), rapid progressors experienced faster CD4 T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1-18 [-0.05 (-0.06; -0.03)] and no significant differences in 18-60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4 T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. CONCLUSION: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4 T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4 T-cell counts at cART initiation. PMID- 26544705 TI - Likely effect of the 2014 Ebola epidemic on HIV care in Liberia. AB - OBJECTIVE: Liberia's health system has been severely struck by the 2014 Ebola epidemic. We aimed to assess the potential effect of this epidemic on the care of HIV patient in two clinics [John F. Kennedy (JFK) and Redemption Hospitals] in Monrovia, which stayed open throughout the epidemic. DESIGN AND METHODS: A preexisting electronic database of HIV patient's follow-up visits was used to estimate three weekly parameters from January 2012 to October 2014: number of visits, number of new patient, and proportion of patients with follow-up delay. We used segmented negative binomial regressions to assess trends before and after the week of the Ebola outbreak defined in June 2014 by WHO. RESULTS: The cumulative number of patients in care comprised 5948 patients with a total of 56 287 visits between January 2012 and October 2014. From June 2014, the number of visit per week, stable since 2012, abruptly decreased (59%) in Redemption (P < 0.001) and progressively decreased by 3% per week in JFK (P < 0.001). In both the clinics, the weekly proportion of patient with follow-up delay sharply increased after the point break from June 2014 (P value < 0.001). From June 2014, a significant decrease in new patients per week occurred in both the clinics: by 57% (P value < 0.001) in Redemption and by 4.6% per week (P value < 0.001) in JFK. CONCLUSION: The Ebola epidemic had a significant effect on HIV care in Monrovia. Given the particular impact on the rate of patients with follow-up delay, a long-term impact is feared. PMID- 26544706 TI - Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AB - OBJECTIVE: The objective of this study is to assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. METHODS: Using data from 5153 HIV-infected women followed prospectively for 1-3 years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHRs) and test interactions between each method and ART use. RESULTS: During follow-up, 9% of women ever used implants, 40% used injectables and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART [aHR 0.06, 95% confidence interval (95% CI) 0.01-0.45] and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed nonstatistically significant reduced effectiveness when concurrently using efavirenz. CONCLUSION: Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use. PMID- 26544707 TI - Lung cancer in patients living with HIV infection. PMID- 26544708 TI - Curing HIV/AIDS beyond hematopoietic stem cell transplant. PMID- 26544709 TI - Aggressive human papillomavirus (HPV)-11-related sinonasal inverted papilloma in an HIV-infected patient and the quadrivalent HPV vaccine: a case report. PMID- 26544710 TI - Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP PCR Assay. AB - Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility. PMID- 26544711 TI - Genotyping of Enterocytozoon bieneusi in Farmed Blue Foxes (Alopex lagopus) and Raccoon Dogs (Nyctereutes procyonoides) in China. AB - Enterocytozoon bieneusi is the most common species of microsporidia found both in humans and animals. Farmed animals, particularly closely associated to humans, may play an important role of zoonotic reservoir in transmitting this disease to humans. The fur industry is a major economic component in some parts of China. To understand the prevalence, genotype variety and zoonotic risk of E. bieneusi in farmed foxes and raccoon dogs, two species of fur animals, fecal specimens of 110 blue foxes and 49 raccoon dogs from Heilongjiang and Jilin provinces in China were examined by internal transcribed spacer (ITS)-based PCR. E. bieneusi was detected in 16.4% (18/110) blue foxes and 4.1% (2/49) raccoon dogs. Altogether, four genotypes of E. bieneusi were identified, including two known genotypes D (n = 13) and EbpC (n = 5), and two novel genotypes named as CHN-F1 (n = 1) in a fox and CHN-R1 (n = 1) in a raccoon dog. Phylogenetic analysis revealed that all the four genotypes were the members of zoonotic group 1. Genotypes D and EbpC were found in humans previously. The findings of zoonotic genotypes of E. bieneusi in the foxes and raccoon dogs suggest these animals infected with E. bieneusi may pose a threat to human health. PMID- 26544712 TI - Connecting Replication and Repair: YoaA, a Helicase-Related Protein, Promotes Azidothymidine Tolerance through Association with Chi, an Accessory Clamp Loader Protein. AB - Elongating DNA polymerases frequently encounter lesions or structures that impede progress and require repair before DNA replication can be completed. Therefore, directing repair factors to a blocked fork, without interfering with normal replication, is important for proper cell function, and it is a process that is not well understood. To study this process, we have employed the chain terminating nucleoside analog, 3' azidothymidine (AZT) and the E. coli genetic system, for which replication and repair factors have been well-defined. By using high-expression suppressor screens, we identified yoaA, encoding a putative helicase, and holC, encoding the Chi component of the replication clamp loader, as genes that promoted tolerance to AZT. YoaA is a putative Fe-S helicase in the XPD/RAD3 family for which orthologs can be found in most bacterial genomes; E. coli has a paralog to YoaA, DinG, which possesses 5' to 3' helicase activity and an Fe-S cluster essential to its activity. Mutants in yoaA are sensitive to AZT exposure; dinG mutations cause mild sensitivity to AZT and exacerbate the sensitivity of yoaA mutant strains. Suppression of AZT sensitivity by holC or yoaA was mutually codependent and we provide evidence here that YoaA and Chi physically interact. Interactions of Chi with single-strand DNA binding protein (SSB) and with Psi were required to aid AZT tolerance, as was the proofreading 3' exonuclease, DnaQ. Our studies suggest that repair is coupled to blocked replication through these interactions. We hypothesize that SSB, through Chi, recruits the YoaA helicase to replication gaps and that unwinding of the nascent strand promotes repair and AZT excision. This recruitment prevents the toxicity of helicase activity and aids the handoff of repair with replication factors, ensuring timely repair and resumption of replication. PMID- 26544713 TI - Killing of Mycolic Acid-Containing Bacteria Aborted Induction of Antibiotic Production by Streptomyces in Combined-Culture. AB - Co-culture of Streptomyces with mycolic acid-containing bacteria (MACB), which we termed "combined-culture," alters the secondary metabolism pattern in Streptomyces and has been a useful method for the discovery of bioactive natural products. In the course of our investigation to identify the inducing factor(s) of MACB, we previously observed that production of pigments in Streptomyces lividans was not induced by factors such as culture extracts or mycolic acids. Although dynamic changes occurred in culture conditions because of MACB, the activation of pigment production by S. lividans was observed in a limited area where both colonies were in direct contact. This suggested that direct attachment of cells is a requirement and that components on the MACB cell membrane may play an important role in the response by S. lividans. Here we examined whether this response was influenced by dead MACB that possess intact mycolic acids assembled on the outer cell membrane. Formaldehyde fixation and gamma-irradiation were used to prepare dead cells that retain their shape and mycolic acids of three MACB species: Tsukamurella pulmonis, Rhodococcus erythropolis, and Rhodococcus opacus. Culturing tests verified that S. lividans does not respond to the intact dead cells of three MACB. Observation of combined-culture by scanning electron microscopy (SEM) indicated that adhesion of live MACB to S. lividans mycelia were a significant interaction that resulted in formation of co-aggregation. In contrast, in the SEM analysis, dead cells were not observed to adhere. Therefore, direct attachment by live MACB cells is proposed as one of the possible factors that causes Streptomyces to alter its specialized metabolism in combined-culture. PMID- 26544714 TI - IRF4-Dependent and IRF4-Independent Pathways Contribute to DC Dysfunction in Lupus. AB - Interferon Regulatory Factors (IRFs) play fundamental roles in dendritic cell (DC) differentiation and function. In particular, IRFs are critical transducers of TLR signaling and dysregulation in this family of factors is associated with the development of autoimmune disorders such as Systemic Lupus Erythematosus (SLE). While several IRFs are expressed in DCs their relative contribution to the aberrant phenotypic and functional characteristics that DCs acquire in autoimmune disease has not been fully delineated. Mice deficient in both DEF6 and SWAP-70 (= Double-knock-out or DKO mice), two members of a unique family of molecules that restrain IRF4 function, spontaneously develop a lupus-like disease. Although autoimmunity in DKO mice is accompanied by dysregulated IRF4 activity in both T and B cells, SWAP-70 is also known to regulate multiple aspects of DC biology leading us to directly evaluate DC development and function in these mice. By monitoring Blimp1 expression and IL-10 competency in DKO mice we demonstrate that DCs in these mice exhibit dysregulated IL-10 production, which is accompanied by aberrant Blimp1 expression in the spleen but not in the peripheral lymph nodes. We furthermore show that DCs from these mice are hyper-responsive to multiple TLR ligands and that IRF4 plays a differential role in in these responses by being required for the TLR4-mediated but not the TLR9-mediated upregulation of IL-10 expression. Thus, DC dysfunction in lupus-prone mice relies on both IRF4 dependent and IRF4-independent pathways. PMID- 26544715 TI - Tripled Readout Slices in Multi Time-Point pCASL Using Multiband Look-Locker EPI. AB - Multi time-point pseudo-continuous arterial spin labelling (pCASL) with a Look Locker EPI readout can sample the signal curve of blood kinetics at multiple time points after the labelling pulse. However, due to signal relaxation of labelled blood, the number of readout slices is limited. The aim of this study is to employ a multiband excitation technique to triple the number of readout slices in multi time-point pCASL. The multiband technique, along with 2-fold in-plane parallel imaging, was incorporated into the Look-Locker EPI for the multi time point sampling of blood kinetic behaviour following the pCASL labelling scheme. The performance evaluation of the multiband and the single-band techniques were performed on four healthy subjects using a 32-channel head RF coil at 3T. Quantitative perfusion maps were analysed using a combination of labelling with and without flow suppression gradients. The perfusion maps provided by the multiband accelerated multi time-point pCASL were in good agreement with the conventional single-band technique. Multiband acceleration caused SNR loss but offered quantitative perfusion maps in 6.23 min with 18 slices compared with 6 slices within the same time period for the single-band method. As conclusion, the multiband technique can successfully triple the number of readout slices while achieving comparable perfusion data in the same measurement time as the conventional single-band readout. PMID- 26544716 TI - Harmonic Scalpel versus Electrocautery Dissection in Modified Radical Mastectomy for Breast Cancer: A Meta-Analysis. AB - BACKGROUND: Despite the common use of conventional electrocautery in modified radical mastectomy for breast cancer, the harmonic scalpel is recently emerging as a dominant surgical instrument for dissection and haemostasis, which is thought to reduce the morbidity, such as seroma and blood loss. But the results of published trials are inconsistent. So we made the meta-analysis to assess the intraoperative and postoperative endpoints among women undergoing modified radical mastectomy with harmonic scalpel or electrocautery. METHODS: A comprehensive literature search of case-control studies from PubMed, MEDLINE, EMBASE and Cochrane Library databases involving modified radical mastectomy with harmonic scalpel or electrocautery was performed. We carried out a meta-analysis of primary endpoints including postoperative drainage, seroma development, intraoperative blood loss and secondly endpoints including operative time and wound complications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the effect size for categorical outcomes and standardised mean differences (SMDs) for continuous outcomes. RESULTS: A total of 11 studies with 702 patients were included for this meta-analysis. There was significant difference in total postoperative drainage (SMD: -0.74 [95%CI: -1.31, -0.16]; P< 0.01), seroma development[OR: 0.49 (0.34, 0.70); P < 0.01], intraoperative blood loss(SMD: -1.14 [95%CI: -1.81,-0.47]; P < 0.01) and wound complications [OR: 0.38 (0.24, 0.59); P < 0.01] between harmonic scalpel dissection and standard electrocautery in modified radical mastectomy for breast cancer. No difference was found as for operative time between harmonic scalpel dissection and standard electrocautery (SMD: 0.04 [95%CI: -0.41, 0.50]; P = 0.85). CONCLUSION: Compared to standard electrocautery, harmonic scalpel dissection presents significant advantages in decreasing postoperative drainage, seroma development, intraoperative blood loss and wound complications in modified radical mastectomy for breast cancer, without increasing operative time. Harmonic scalpel can be recommended as a preferential surgical instrument in modified radical mastectomy. PMID- 26544717 TI - Nutritional Issues in the Short Bowel Syndrome - Total Parenteral Nutrition, Enteral Nutrition and the Role of Transplantation. AB - In this review, I focus on the extreme of the short bowel syndrome where the loss of intestine is so great that patients cannot survive without intravenous feeding. This condition is termed short bowel intestinal failure. The review outlines the principles behind diagnosis, assessing prognosis and management. The advent of intravenous feeding (parenteral nutrition) in the 1970s enabled patients with massive (>90%) bowel resection to survive for the first time and to be rehabilitated back into normal life. To achieve this, central venous catheters were inserted preferably into the superior vena cava and intravenous infusions were given overnight so that the catheter could be sealed by day in order to maximize ambulation and social integration. However, quality of life has suffered by the association of serious complications related to permanent catheterization mostly in the form of septicemias, thrombosis, metabolic intolerance and liver failure - from the unphysiological route of nutrient delivery. This has led to intense research into restoring gut function. In addition to dietary modifications and therapeutic suppression of motility, novel approaches have been aimed at enhancing the natural adaptation process, first with recombinant growth hormone and more recently with gut-specific glucagon-like peptide-2 analogues, e.g. teduglutide. These approaches have met with some success, reducing the intravenous caloric needs by approximately 500 kcal/day. In controlled clinical trials, teduglutide has been shown to permit >20% reductions in intravenous requirements in over 60% of patients after 6 months of treatment. Some patients have been weaned, but more have been able to drop infusion days. The only approach that predictably can get patients with massive intestinal loss completely off parenteral nutrition is small bowel transplantation, which, if successful (1-year survival for graft and host >90%) is accompanied by dramatic improvements in quality of life. PMID- 26544718 TI - Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue. RESULTS: The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 +/- 0.017, AT: 0.38 +/- 0.012, AMI: 0.375 +/- 0.018 and AMI + AT: 0.38 +/- 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0). CONCLUSION: In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats. PMID- 26544719 TI - Effect of a Wide Stance on Block Start Performance in Sprint Running. AB - This study aimed to clarify the effect of widened stance width at the set position during the block start phase in sprint running on kinematics and kinetics at the hip joint and block-induced power. Fourteen male sprinters volunteered to participate in this study. They performed three block-start trials with a normal stance width (25 +/- 1 cm, normal condition) and a widened stance width (45 +/- 2 cm, widened condition) at the set position. The block start movements were recorded at 250 Hz with high-speed cameras and the ground reaction forces at 1250 Hz with force plates. During the block phase in the widened condition, the hip abduction and external rotation angles in both legs were significantly larger and smaller, respectively, than those in the normal condition. The positive peak value of the hip power in the rear leg was significantly greater in the widened condition than that in the normal condition. However, no significant difference was seen in the normalized block-induced power between the widened and normal conditions. We conclude that a widened stance width at the set position affects the hip-joint kinematics and rear hip power generation during the block start phase, but no effect on the block-induced power when considering sprinting performance during the whole block start phase. PMID- 26544720 TI - Conformation-selective coordination-driven self-assembly of a ditopic donor with Pd(II) acceptors. AB - Coordination-driven self-assembly of 3-(5-(pyridin-3-yl)-1H-1,2,4-triazol-3 yl)pyridine (L) was investigated with 90 degrees cis-blocked Pd(II) acceptors and tetratopic Pd(NO3)2. Although the ligand is capable of binding in several different conformations (acting as a ditopic donor through the pyridyl nitrogens), the experimental results (including X-ray structures) showed that it adopts a particular conformation when it binds with 90 degrees cis-blocked Pd(II) acceptors (two available sites) to yield [2 + 2] self-assembled macrocycles. On the other hand, with Pd(NO3)2 (where four available sites are present) a different conformer of the same donor was selectively bound to form a molecular cubic cage. The experimental findings were corroborated well with the density functional theory (B3LYP) calculations. The tetratopic Pd(NO3)2 yielded a [6 + 12] self-assembled Pd6L12 molecular cube, which contains a potential void occupied by nitrate and perchlorate ions. Being a triazole based ligand, the free space inside the cage is enriched with several sp(2) hybridised nitrogen atoms with lone pairs of electrons to act as Lewis basic sites. Knoevenagel condensation reactions of several aromatic aldehydes with active methylene compounds were successfully performed in reasonably high yields in the presence of the cage. PMID- 26544722 TI - Correction: Predicting Falls in Parkinson Disease: What Is the Value of Instrumented Testing in OFF Medication State? PMID- 26544721 TI - Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly. AB - The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf), supporting SMYD1b as an assembly protein during sarcomere formation. PMID- 26544723 TI - High-Dynamic-Range CT Reconstruction Based on Varying Tube-Voltage Imaging. AB - For complicated structural components characterized by wide X-ray attenuation ranges, the conventional computed tomography (CT) imaging using a single tube voltage at each rotation angle cannot obtain all structural information. This limitation results in a shortage of CT information, because the effective thickness of the components along the direction of X-ray penetration exceeds the limitation of the dynamic range of the X-ray imaging system. To address this problem, high-dynamic-range CT (HDR-CT) reconstruction is proposed. For this new method, the tube's voltage is adjusted several times to match the corresponding effective thickness about the local information from an object. Then, HDR fusion and HDR-CT are applied to obtain the full reconstruction information. An accompanying experiment demonstrates that this new technology can extend the dynamic range of X-ray imaging systems and provide the complete internal structures of complicated structural components. PMID- 26544724 TI - Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production. AB - Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN '93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2 isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (p<0.0001), with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159) or nitrite excretion (p = 0.670). Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid. PMID- 26544726 TI - The Anti-Tumor Activity of Succinyl Macrolactin A Is Mediated through the beta Catenin Destruction Complex via the Suppression of Tankyrase and PI3K/Akt. AB - Accumulated gene mutations in cancer suggest that multi-targeted suppression of affected signaling networks is a promising strategy for cancer treatment. In the present study, we report that 7-O-succinyl macrolactin A (SMA) suppresses tumor growth by stabilizing the beta-catenin destruction complex, which was achieved through inhibition of regulatory components associated with the complex. SMA significantly reduced the activities of PI3K/Akt, which corresponded with a decrease in GSK3beta phosphorylation, an increase in beta-catenin phosphorylation, and a reduction in nuclear beta-catenin content in HT29 human colon cancer cells. At the same time, the activity of tankyrase, which inhibits the beta-catenin destruction complex by destabilizing the axin level, was suppressed by SMA. Despite the low potency of SMA against tankyrase activity (IC50 of 50.1 MUM and 15.5 MUM for tankyrase 1 and 2, respectively) compared to XAV939 (IC50 of 11 nM for tankyrase 1), a selective and potent tankyrase inhibitor, SMA had strong inhibitory effects on beta-catenin-dependent TCF/LEF1 transcriptional activity (IC50 of 39.8 nM), which were similar to that of XAV939 (IC50 of 28.1 nM). In addition to suppressing the colony forming ability of colon cancer cells in vitro, SMA significantly inhibited tumor growth in CT26 syngenic and HT29 xenograft mouse tumor models. Furthermore, treating mice with SMA in combination with 5-FU in a colon cancer xenograft model or with cisplatin in an A549 lung cancer xenograft model resulted in greater anti-tumor activity than did treatment with the drugs alone. In the xenograft tumor tissues, SMA dose dependently inhibited nuclear beta-catenin along with reductions in GSK3beta phosphorylation and increases in axin levels. These results suggest that SMA is a possible candidate as an effective anti-cancer agent alone or in combination with cytotoxic chemotherapeutic drugs, such as 5-FU and cisplatin, and that the mode of action for SMA involves stabilization of the beta-catenin destruction complex through inhibition of tankyrase and the PI3K/Akt signaling pathway. PMID- 26544727 TI - Trophic transfer of radioisotopes in Mediterranean sponges through bacteria consumption. AB - Numerous field studies highlighted the capacities of marine sponges to bioaccumulate trace elements and assessed their potential as biomonitors of the marine environment. Experimental works demonstrated that dissolved metals and radionuclides can be taken up directly by sponge tissues but, to the best of our knowledge, little is known on the contribution of the dietary pathway through the consumption of contaminated bacteria considered as one of the trophic source in sponge diet. Objectives of this work are to study trophic transfer of radiotracers (110m)Ag, (241)Am, (109)Cd, (57)Co, (134)Cs, (54)Mn and (65)Zn from the marine bacteria Pseudomonas stutzeri to the Mediterranean sponges Aplysina cavernicola and Ircinia oros. P. stutzeri efficiently bioaccumulated trace elements in our culture experimental conditions with CF comprised between 10(5) and 10(7) after 48 h of growth in radiolabeled medium. When fed with these radiolabelled bacteria, A. cavernicola took up around 60% of radiotracers accumulated in trophic source except (134)Cs for which only 8% has been transferred from bacteria to sponge. Contrasting to this, I. oros retained only 7% of (110m)Ag, (109)Cd and (65)Zn counted in bacteria, but retained 2-fold longer accumulated metals in its tissues. The sponge inter-specific differences of accumulation and depuration following a trophic exposure are discussed with respect to the structure and the clearance capacities of each species. PMID- 26544725 TI - Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents. AB - BACKGROUND: Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS: We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS: The mean (+/-SD) baseline age of the participants was 17+/-1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS: In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micronutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.). PMID- 26544728 TI - MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data. AB - Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features. PMID- 26544729 TI - Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt. AB - BACKGROUND AND PURPOSE: Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. The possible working mechanisms of these haloperidol derivatives were also explored. EXPERIMENTAL APPROACH: Novel calcium antagonists were synthesized by amination. Compounds were screened for their activity of vasodilation on isolated thoracic aortic ring of rats. Their cardiac side effects were explored. The patch-clamp, confocal laser microscopy and the computer-fitting molecular docking experiments were employed to investigate the possible working mechanisms of these calcium antagonists. RESULTS: The novel calcium antagonists, X1, X2 and X3 showed stronger vasodilation effect and less cardiac side effect than that of classical calcium antagonists. They blocked L type calcium channels with an potent effect order of X1 > X2 > X3. Consistently, X1, X2 and X3 interacted with different regions of Ca2+-CaM-CaV1.2 with an affinity order of X1 > X2 > X3. CONCLUSIONS: The new halopedidol derivatives X1, X2 and X3 are novel calcium antagonists with stronger vasodilation effect and less cardiac side effect. They could have wide clinical application. PMID- 26544730 TI - Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription. AB - Abundant evidence has demonstrated critical roles of KLF5 in regulating cell proliferation in various cancers, however, its additional roles in other aspects of cancer development remain to be further clarified. In this study, we found that KLF5 was essential for cancer cell-endothelial cell interaction in vitro and tumor angiogenesis in nude mice based on lentivirus-mediated KLF5 knockdown bladder cancer cell models. Moreover, KLF5 insufficiency abolished the ability of bladder cancer cells to induce neovascularization in rabbit cornea. Mechanistically, the pro-angiogenic factor VEGFA was identified as a direct downstream target of KLF5, which bound to GC-boxes and CACCC elements of VEGFA promoter and regulated its transcriptional activity. In addition, there was a positive correlation between KLF5 and VEGFA expression in human bladder cancer tissues by immunohistochemistry assay and statistical analysis from TCGA and GEO data. Furthermore, we found that two pivotal pathways in bladder cancer, RTKs/RAS/MAPK and PI3K/Akt, might convey their oncogenic signaling through KLF5 VEGFA axis. Taken together, our results indicate that KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription and suggest that KLF5 could be a novel therapeutic target for angiogenesis inhibition in bladder cancer. PMID- 26544731 TI - pERK/pAkt phenotyping in circulating tumor cells as a biomarker for sorafenib efficacy in patients with advanced hepatocellular carcinoma. AB - Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, therapeutic response to sorafenib was not equal among HCC patients. Here we present a novel system to provide quantitative information concerning sorafenib-related targets by simultaneous detection of phosphorylated ERK (pERK) and pAkt expressions in circulating tumor cells (CTCs) isolated from HCC patients. Our results showed that 90.0% of patients had a molecular classification of tissues concordant with that of CTCs. CTC counts showed a shaper decline in patients with pERK+/pAkt- CTCs after two weeks of sorafenib treatment (P < 0.01). Disease control rates were significantly different between patients with pERK+/pAkt- CTCs (11/15; 73.3%) and those without (13/44; 29.5%) (P < 0.05). Univariate and multivariate analysis indicated pERK+/pAkt- CTCs as an independent predictive factor of progression-free survival (PFS) (hazard ratio = 9.389; P < 0.01). PFS correlated with the proportion of pERK+/pAkt- CTCs (r = 0.968, P < 0.01), and was higher in patients with >= 40% pERK+/pAkt- CTCs compared to those with < 40% (8.4 vs. 1.3 mo; P < 0.05). In a validation set of twenty HCC patients, CTCs from patients with >= 40% pERK+/pAkt- CTCs had significantly higher inhibition rates of spheroid formation compared to those with < 40% (61.2 vs. 19.8%; P < 0.01). Our findings demonstrated that CTCs can be used in place of tumor tissue for characterization of pERK/pAkt expression. pERK+/pAkt- CTCs are most sensitive to sorafenib and an independent predictive factor of PFS in HCC patients treated with sorafenib. PMID- 26544733 TI - Potential Bone to Implant Contact Area of Short Versus Standard Implants: An In Vitro Micro-Computed Tomography Analysis. AB - AIM: To compare the available potential bone-implant contact (PBIC) area of standard and short dental implants by micro-computed tomography (MUCT) assessment. METHODS: Three short implants with different diameters (4.5 * 6 mm, 4.1 * 7 mm, and 4.1 * 6 mm) and 2 standard implants (3.5 * 10 mm and 3.3 * 9 mm) with diverse design and surface features were scanned with MUCT. Cross-sectional images were obtained. Image data were manually processed to find the plane that corresponds to the most coronal contact point between the crestal bone and implant. The available PBIC was calculated for each sample. Later on, the cross sectional slices were processed by a 3-dimensional (3D) software, and 3D images of each sample were used for descriptive analysis and display the microtopography and macrotopography. RESULTS: The wide-diameter short implant (4.5 * 6 mm) showed the higher PBIC (210.89 mm) value followed by the standard (178.07 mm and 185.37 mm) and short implants (130.70 mm and 110.70 mm). CONCLUSIONS: Wide-diameter short implants show a surface area comparable with standard implants. Micro-CT analysis is a promising technique to evaluate surface area in dental implants with different macrodesign, microdesign, and surface features. PMID- 26544732 TI - Transforming growth factor-beta1 polymorphisms and graft-versus-host disease risk: a meta-analysis. AB - Some studies have demonstrated that transforming growth factor (TGF)-beta polymorphisms may have an important role in the pathological process of graft versus-host disease (GVHD). However, the results are not consistent. Thus, we performed a meta-analysis. Online databases were searched to obtain relevant articles published up until May 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Donors (OR=0.56; 95%CI, 0.32-0.98; P=0.04) and recipients (OR=0.73; 95%CI, 0.63-0.85; P<0.0001) with TGF-beta1 rs1800469 polymorphism showed decreased GVHD risk, respectively. Donors with TGF-beta1 rs1800470 polymorphism were also observed to have lower GVHD risk (OR=0.65; 95%CI, 0.46-0.94; P=0.02). However, TGF-beta1 rs1800470 polymorphism in recipients was not associated with GVHD risk (OR=1.28; 95%CI, 0.81-2.01; P=0.29). No significant heterogeneity was found in the meta analysis. This meta-analysis suggests that donors or recipients with TGF-beta1 rs1800469 polymorphism and donors with TGF-beta1 rs1800470 polymorphism might be associated with reduced GVHD risk. PMID- 26544734 TI - Histomorphometric Analysis of Contaminated Autogenous Tooth Graft Materials After Various Sterilization. AB - PURPOSE: The purpose of this study was to evaluate histomorphometrically contaminated autogenous tooth graft materials, which were resterilized. MATERIALS AND METHODS: The intentional defects (diameter: 8 mm, depth: 4 mm) were formed around implant fixture on the iliac crest of 6 mongrel dogs. Autogenous tooth graft materials were made by extracted premolars. After the contamination of the tooth materials, graft procedure was performed; no contaminated group (control group), contaminated groups (nonsterilization group [group 1], ethylene oxide [EO] gas group [group 2], and autoclave group [group 3]). The bone-to-implant contact (BIC) and the new bone formation rate (NBFR) were evaluated after sacrifice. RESULTS: The BIC and NBFR of groups 1 and 3 were significantly lower than the control group after 4 weeks. The BIC and NBRF of group 3 were significantly lower than the control group after 8 weeks. However, the BIC and NBRF of group 2 was not significantly different comparing with the control group after 4 and 8 weeks. CONCLUSION: Sterilization using EO gas may be more favorable than high-pressure sterilization in cases the reuse of contaminated autogenous tooth graft materials. PMID- 26544735 TI - Numerical and experimental investigations for the evaluation of the wear coefficient of reverse total shoulder prostheses. AB - In the present study, numerical and experimental wear investigations on reverse total shoulder arthroplasties (RTSAs) were combined in order to estimate specific wear coefficients, currently not available in the literature. A wear model previously developed by the authors for metal-on-plastic hip implants was adapted to RTSAs and applied in a double direction: firstly, to evaluate specific wear coefficients for RTSAs from experimental results and secondly, to predict wear distribution. In both cases, the Archard wear law (AR) and the wear law of UHMWPE (PE) were considered, assuming four different k functions. The results indicated that both the wear laws predict higher wear coefficients for RTSA with respect to hip implants, particularly the AR law, with k values higher than twofold the hip ones. Such differences can significantly affect predictive wear model results for RTSA, when non-specific wear coefficients are used. Moreover, the wear maps simulated with the two laws are markedly different, although providing the same wear volume. A higher wear depth (+51%) is obtained with the AR law, located at the dome of the cup, while with the PE law the most worn region is close to the edge. Taking advantage of the linear trend of experimental volume losses, the wear coefficients obtained with the AR law should be valid despite having neglected the geometry update in the model. PMID- 26544736 TI - I'm only sleeping. PMID- 26544737 TI - Chronic inflammation: a new therapeutic target for post-traumatic stress disorder? PMID- 26544738 TI - Mental health in emergency response: lessons from Ebola. PMID- 26544739 TI - Reducing extramedical use and harms of pharmaceutical opioids: the potential role of abuse-deterrent formulations. PMID- 26544740 TI - The contemporary state of service-user-led research. PMID- 26544741 TI - Corrections. PMID- 26544742 TI - Registration and definitions of mental disorders in Swedish survivors of the 2004 southeast Asia tsunami--Authors' response. PMID- 26544743 TI - Registration and definitions of mental disorders in Swedish survivors of the 2004 southeast Asia tsunami. PMID- 26544745 TI - The National Psychosis Unit: curing the incurable. PMID- 26544746 TI - Simon Baron-Cohen: cultivating diversity. PMID- 26544748 TI - The charm's wound up. PMID- 26544747 TI - "A touch of eternity". PMID- 26544749 TI - Inflammatory markers in post-traumatic stress disorder: a systematic review, meta analysis, and meta-regression. AB - BACKGROUND: Studies investigating inflammatory markers in post-traumatic stress disorder (PTSD) have yielded mixed results. The aim of our study was to compare concentrations of inflammatory markers in patients with PTSD compared with healthy controls. METHODS: We did a meta-analysis and meta-regression of studies comparing inflammatory markers between patients with PTSD and healthy controls by searching PubMed, Embase, Scopus, Web of Science, and PsycINFO for articles published between Jan 1, 1960, and April 7, 2015. From eligible studies (ie, cross-sectional studies or baseline data from longitudinal studies of peripheral blood cytokine concentrations that compared adults with PTSD with healthy controls), we extracted outcomes of interest, such as mean and SD of peripheral blood cytokines, the time of day blood was collected, whether the study allowed patients with comorbid major depressive disorder in the PTSD group, whether patients were medication free, and severity of PTSD symptoms. We undertook meta analyses whenever values of inflammatory markers were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesise the effect size (assessed by standardised mean difference [SMD]) across studies. FINDINGS: 8057 abstracts were identified and 20 studies were included. Interleukin 6 (SMD 0.88; p=0.0003), interleukin 1beta (SMD 1.42; p=0.045), and interferon gamma (SMD 0.49; p=0.002) levels were higher in the PTSD group than in healthy controls. Subgroup meta-analysis of patients who were not given medication showed higher tumour necrosis factor alpha (TNFalpha; SMD 0.69, 95% CI 0.35-1.02; p<0.0001) in the PTSD group than the control group in addition to the aforementioned cytokines. TNFalpha (SMD 1.32, 0.13-2.50; p=0.003), interleukin 1beta (SMD 2.35, 0.01-4.68; p=0.048), and interleukin 6 (SMD 1.75, 0.97-2.53; p<0.0001) levels remained increased in the PTSD group in a subgroup meta-analysis of studies that excluded comorbid major depressive disorder. Illness duration was positively associated with interleukin 1beta levels (b=0.33, p<0.0001) and severity with interleukin 6 (b=0.02, p=0.042). A model composed of several variables-presence of comorbid major depressive disorder, use of psychotropic medications, assay used, and time of day blood was collected explained the large amount of heterogeneity between interleukin 1beta, interleukin 6, and C-reactive protein studies. Egger's linear regression test revealed a potential publication bias for interleukin 1beta. Additionally, for most inflammatory markers, study heterogeneity was reported to be high (I(2)>75%). INTERPRETATION: PTSD is associated with increased interleukin 6, interleukin 1beta, TNFalpha, and interferon gamma levels. This information might be useful for consideration of chronic low-grade inflammation as a potential target or biomarker in PTSD treatment. Use of psychotropic medication and presence of comorbid major depressive disorder were important moderators that might explain the inconsistency between results of previous studies. Our search strategy used a range of databases and we made exhaustive effort to acquire data by contacting the authors. Notably, high levels of between-study heterogeneity were recorded for most cytokine variables measured in our analysis. However, meta regression analysis could explain a large amount of this heterogeneity. FUNDING: None. PMID- 26544750 TI - Identifying the lost generation of adults with autism spectrum conditions. AB - Autism spectrum conditions comprise a set of early-onset neurodevelopmental syndromes with a prevalence of 1% across all ages. First diagnosis in adulthood has finally become recognised as an important clinical issue due to the increasing awareness of autism, broadening of diagnostic criteria, and the introduction of the spectrum concept. Thus, the idea of a lost generation of people who were previously excluded from a diagnosis of classic autism has arisen. Making a first diagnosis of autism spectrum conditions in adults can be challenging for practical reasons (eg, no person to provide a developmental history), developmental reasons (eg, the acquisition of learnt or camouflaging strategies), and clinical reasons (eg, high frequency of co-occurring disorders). The diagnostic process includes referral, screening, interviews with informants and patients, and functional assessments. In delineating differential diagnoses, true comorbidities, and overlapping behaviour with other psychiatric diagnoses, particular attention should be paid to anxiety, depression, obsessive-compulsive disorder, psychosis, personality disorders, and other neurodevelopmental disorders. Possible misdiagnosis, especially in women, should be explored. The creation of supportive, accepting, and autism-friendly social and physical environments is important and requires a coordinated effort across agencies and needs support from government policies. PMID- 26544751 TI - Effects of sleep deprivation on inhibitory biomarkers of schizophrenia: implications for drug development. AB - Development of drugs for the treatment of the clinical symptoms and cognitive deficits of schizophrenia is unsatisfactory, with many initially promising compounds not showing beneficial effects in clinical studies. Experimental model systems of schizophrenia combined with well-validated biomarkers are urgently needed to provide early indicators of effectiveness. Herein, we argue that experimentally controlled sleep deprivation represents a translational model system that can be studied in combination with neurocognitive biomarkers. Specifically, we review data on the psychotomimetic effects of sleep deprivation in healthy human beings and provide evidence of the psychosis-like deficits in translational inhibitory biomarkers-prepulse inhibition and antisaccades-that occur after sleep deprivation. These data support the use of the sleep deprivation model in combination with biomarkers with excellent psychometric properties and well-characterised neural mechanisms, such as prepulse inhibition and antisaccades, to substantially advance development of drugs with antipsychotic or pro-cognitive effects. PMID- 26544752 TI - A failure to communicate: psychiatry's split-care experience. PMID- 26544753 TI - UN CRPD: equal recognition before the law. PMID- 26544754 TI - Balance your humours. PMID- 26544755 TI - Prognostic Impact of Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy. AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is considered an indicator of systemic inflammation and may predict prognosis in colorectal cancer. In this study, we examined the prognostic impact of NLR in patients with locally advanced low rectal cancer treated with neoadjuvant chemoradiotherapy (NACRT) followed by surgery. METHODS: From 2004 to 2012, we analyzed 201 consecutive patients with locally advanced low rectal cancer below the peritoneal reflection who underwent NACRT and curative resection. Blood samples were obtained before NACRT. NLRs were dichotomized using a cut-off value of 3.0, which was chosen based on receiver operating characteristic analysis and previous studies, and we analyzed their relationship with clinical outcomes. RESULTS: Forty-four (21.9%) patients had a high NLR. Moreover, a high NLR was significantly associated with elevated carcinoembryonic antigen levels before NACRT (p = 0.0154). Multivariate analysis showed that a high NLR was independently associated with worse overall survival (hazard ratio (HR) 3.38, p = 0.012). In contrast, a high NLR was not significantly associated with relapse-free survival (HR 1.073, p = 0.8438). The post-recurrence survival between patients with high and low NLRs was significantly different (p = 0.0370). CONCLUSIONS: A high NLR (>=3.0) prior to NACRT was independently associated with poor prognosis in patients with locally advanced low rectal cancer treated with NACRT and radical resection. PMID- 26544756 TI - Recent Advances in Two-Dimensional Materials beyond Graphene. AB - The isolation of graphene in 2004 from graphite was a defining moment for the "birth" of a field: two-dimensional (2D) materials. In recent years, there has been a rapidly increasing number of papers focusing on non-graphene layered materials, including transition-metal dichalcogenides (TMDs), because of the new properties and applications that emerge upon 2D confinement. Here, we review significant recent advances and important new developments in 2D materials "beyond graphene". We provide insight into the theoretical modeling and understanding of the van der Waals (vdW) forces that hold together the 2D layers in bulk solids, as well as their excitonic properties and growth morphologies. Additionally, we highlight recent breakthroughs in TMD synthesis and characterization and discuss the newest families of 2D materials, including monoelement 2D materials (i.e., silicene, phosphorene, etc.) and transition metal carbide- and carbon nitride-based MXenes. We then discuss the doping and functionalization of 2D materials beyond graphene that enable device applications, followed by advances in electronic, optoelectronic, and magnetic devices and theory. Finally, we provide perspectives on the future of 2D materials beyond graphene. PMID- 26544757 TI - Histopathological alterations in the striatum caused by Karwinskia humboldtiana (Buckthorn) fruit in an experimental model of peripheral neuropathy. AB - The accidental ingestion of Karwinskia humboldtiana (Kh) fruit in humans and animals causes chronic or acute intoxication. Acute poisoning induces respiratory failure that progresses rapidly to death. Studies in animals intoxicated with Kh describe lesions in cerebral cortex, cerebellum, spinal cord, hippocampus and caudate nucleus. Kh intoxication in Wistar rats models the sub-lethal clinical phase observed in humans. Considering these reports, the present study analyzed the histopathological alterations within the striatum following experimental Kh intoxication. Twenty Wistar rats were divided into three groups (n =5) and were intoxicated with Kh fruit. A control group (n =5) was included. Animals were euthanized at several time points (48, 58 and 170 days post-intoxication). The brain was collected, divided and processed for conventional histology or electron microscopy. Sections were stained with hematoxylin and eosin, cresyl violet, Kluver-Barrera, and toluidine blue. Immunolabeling was performed for glial cells in the striatum, and the samples were analyzed with light microscopy. Morphometric and statistical analyses were performed. In control group, neurons, axon bundles and neuropil had a normal appearance. At 48 days, hyperchromic neurons with apparent decreased size were observed interspersed among the normal neurons. At 58 days, we observed an increased number of hyperchromic neurons and disorganization of the myelin sheath and neuropil. At 170 days, these alterations persisted in the paralysis group. In treated groups, we observed signs of gliosis and increased axonal diameters. This study is the first report that describes the histopathological alterations within the striatum caused by chronic intoxication with Kh fruit in the Wistar rat. PMID- 26544758 TI - Extracorporeal membrane oxygenation in avalanche victim with deep hypothermia and circulatory arrest. PMID- 26544759 TI - Effect of Separation Temperature on Structure Specific Glycan Migration in Capillary Electrophoresis. AB - Temperature dependent differential migration shifts were studied in capillary electrophoresis between linear (maltooligosaccharides) and branched (sialylated, neutral and core fucosylated biantennary IgG glycans) carbohydrates. Background electrolytes without as well as with low and high molecular weight additives (ethylene glycol, linear polyacrylamide and poly(ethylene oxide)) were investigated for this phenomena in the temperature range of 20-50 degrees C. Glucose unit (GU) value shifts were observed with increasing temperature for the all IgG glycans both in additive-free and additive-containing background electrolytes, emphasizing the importance of tight temperature control during glycosylation analysis by capillary electrophoresis. The activation energy concept was applied to understand the structure specific electrophoretic migration of the different sugar molecules. Activation energy values were derived from the slopes of the Arrhenius plots of logarithmic mobility vs reciprocal absolute temperature and compared for the linear and branched sugars as well as for the various background electrolyte additives. PMID- 26544760 TI - Bidirectional Transformation of a Metamorphic Protein between the Water-Soluble and Transmembrane Native States. AB - The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural reorganization generating cytolytic transmembrane nanopores conducive to cell death. So far, the reverse transformation from the native transmembrane conformation to the native water-soluble conformation has not been reported. We describe the use of detergents with different physicochemical properties to achieve the spontaneous conversion of transmembrane pores of FraC back into the initial water-soluble state. Thermodynamic and kinetic stability data suggest that specific detergents cause an asymmetric change in the energy landscape of the protein, allowing the bidirectional transformation of a membrane protein. PMID- 26544761 TI - Investigation of Praseodymium Fluorides: A Combined Matrix-Isolation and Quantum Chemical Study. AB - The chemistry of the lanthanides is mostly dominated by compounds in the oxidation state +III. Only few compounds of Ce, Pr, and Tb are known with the metal in the +IV oxidation state. Removal of the last f-electron on praseodymium +IV would lead to a closed-shell system with formal oxidation state V. In this work we investigated the stability of the PrF5 molecule by theory and matrix isolation techniques through the reaction of laser-ablated praseodymium atoms with fluorine in excess of neon, argon, krypton, or neat fluorine. Besides the known PrF3 molecule, unreported IR bands for PrF4 could be observed, and there is evidence for the formation of PrF and PrF2 but not for the formation of PrF5. PMID- 26544762 TI - Antidiabetic, Chemical, and Physical Properties of Organic Vanadates as Presumed Transition-State Inhibitors for Phosphatases. AB - Studies of antidiabetic vanadium compounds, specifically the organic vanadate esters, are reviewed with regard to their chemistry and biological properties. The compounds are described from the perspective of how the fundamental chemistry and properties of organic vanadate esters impact their effects as inhibitors for phosphatases based on the structural information obtained from vanadium phosphatase complexes. Vanadium compounds have been reported to have antidiabetic properties for more than a century. The structures and properties of organic vanadate complexes are reviewed, and the potency of such vanadium coordination complexes as antidiabetic agents is described. Because such compounds form spontaneously in aqueous environments, the reactions with most components in any assay or cellular environment has potential to be important and should be considered. Generally, the active form of vanadium remains elusive, although studies have been reported of a number of promising vanadium compounds. The description of the antidiabetic properties of vanadium compounds is described here in the context of recent characterization of vanadate-phosphatase protein structures by data mining. Organic vanadate ester compounds are generally four coordinate or five coordinate with the former being substrate analogues and the latter being transition-state analogue inhibitors. These studies demonstrated a framework for characterization of five-coordinate trigonal bipyramidal vanadium inhibitors by comparison with the reported vanadium-protein phosphatase complexes. The binding of the vanadium to the phosphatases is either as a five coordinate exploded transition-state analogue or as a high energy intermediate, respectively. Even if potency as an inhibitor requires trigonal bipyramidal geometry of the vanadium when bound to the protein, such geometry can be achieved upon binding from compounds with other geometries. Desirable properties of ligands are identified and analyzed. Ligand interactions, as reported in one peptidic substrate, are favorable so that complementarity between phosphatase and coordinating ligand to the vanadium can be established resulting in a dramatic enhancement of the inhibitory potency. These considerations point to a frameshift in ligand design for vanadium complexes as phosphatase inhibitors and are consistent with other small molecule having much lower affinities. Combined, these studies do suggest that if effective delivery of potentially active antidiabetic compound such a the organic vanadate peptidic substrate was possible the toxicity problems currently reported for the salts and some of the complexes may be alleviated and dramatic enhancement of antidiabetic vanadium compounds may result. PMID- 26544763 TI - Brain Region-Specific Dynamics of On-Tissue Protein Digestion Using MALDI Mass Spectrometry Imaging. AB - In mass spectrometry imaging (MSI), on-tissue proteolytic digestion is performed to access larger protein species and to assign protein identities through matching the detected peaks with those obtained by LC-MS/MS analyses of tissue extracts. The on-tissue proteolytic digestion also allows the analysis of proteins from formalin-fixed, paraffin-embedded tissues. For these reasons, on tissue digestion-based MSI is frequently used in clinical investigations, for example, to determine changes in protein content and distribution associated with a disease. In this work, we sought to investigate the completeness and uniformity of the digestion in on-tissue digestion MSI. On the basis of an extensive experiment investigating three groups with varying incubation times: (i) 1.5 h, (ii) 3 h, and (iii) 18 h, we have found that longer incubation times improve the repeatability of the analyses. Furthermore, we discovered morphology-associated differences in the completeness of the proteolysis for short incubation times. These results support the notion that a more complete proteolysis allows better quantitation. PMID- 26544764 TI - Can Highly Oxidized Organics Contribute to Atmospheric New Particle Formation? AB - Highly oxidized organic molecules may play a critical role in new-particle formation within Earth's atmosphere along with sulfuric acid, which has long been considered as a key compound in this process. Here we explore the interactions of these two partners, using quantum chemistry to find the formation free energies of heterodimers and trimers as well as the fastest evaporation rates of (2,2) tetramers. We find that the heterodimers are more strongly bound than pure sulfuric acid dimers. Their stability correlates well with the oxygen to carbon ratio of the organics, their volatility, and the number of hydrogen bonds formed. Most of the stable trimers contain one sulfuric acid and two organics (1,2), whereas many (2,2) tetramers evaporate quickly, probably due to the stability of (1,2) clusters. This finding agrees with recent experimental studies that show how new-particle formation involving oxidized organics and sulfuric acid may be rate-limited by activation of (1,2) trimers, confirming the importance of this process in the atmosphere. PMID- 26544766 TI - The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients. AB - Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as >=5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for >=6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% >=3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy. PMID- 26544765 TI - Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of "Shapeshifting" Properties. AB - The 2,4'- and 4,4'-linked variants of the cytotoxic agent secalonic acid A and their analogues have been synthesized. Kinetic resolution of an unprotected tetrahydroxanthone scaffold followed by copper-mediated biaryl coupling allowed for efficient access to these compounds. Evaluation of the "shapeshifting" properties of 2,2'-, 2,4'-, and 4,4'-linked variants of the secalonic acids A in a polar solvent in conjunction with assays of the compounds against select cancer cell lines was conducted to study possible correlations between linkage variation and cytotoxicity. PMID- 26544767 TI - Intraoperative mapping during repeat awake craniotomy reveals the functional plasticity of adult cortex. AB - OBJECT To avoid iatrogenic injury during the removal of intrinsic cerebral neoplasms such as gliomas, direct electrical stimulation (DES) is used to identify cortical and subcortical white matter pathways critical for language, motor, and sensory function. When a patient undergoes more than 1 brain tumor resection as in the case of tumor recurrence, the use of DES provides an unusual opportunity to examine brain plasticity in the setting of neurological disease. METHODS The authors examined 561 consecutive cases in which patients underwent DES mapping during surgery forglioma resection. "Positive" and "negative" sites discrete cortical regions where electrical stimulation did (positive) or did not (negative) produce transient sensory, motor, or language disturbance-were identified prior to tumor resection and documented by intraoperative photography for categorization into functional maps. In this group of 561 patients, 18 were identified who underwent repeat surgery in which 1 or more stimulation sites overlapped with those tested during the initial surgery. The authors compared intraoperative sensory, motor, or language mapping results between initial and repeat surgeries, and evaluated the clinical outcomes for these patients. RESULTS A total of 117 sites were tested for sensory (7 sites, 6.0%), motor (9 sites, 7.7%), or language (101 sites, 86.3%) function during both initial and repeat surgeries. The mean interval between surgical procedures was 4.1 years. During initial surgeries, 95 (81.2%) of 117 sites were found to be negative and 22 (18.8%) of 117 sites were found to be positive. During repeat surgeries, 103 (88.0%) of 117 sites were negative and 14 (12.0%) of 117 were positive. Of the 95 sites that were negative at the initial surgery, 94 (98.9%) were also negative at the repeat surgery, while 1 (1.1%) site was found to be positive. Of the 22 sites that were initially positive, 13 (59.1%) remained positive at repeat surgery, while 9 (40.9%) had become negative for function. Overall, 6 (33.3%) of 18 patients exhibited loss of function at 1 or more motor or language sites between surgeries. Loss of function at these sites was not associated with neurological impairment at the time of repeat surgery, suggesting that neurological function was preserved through neural circuit reorganization or activation of latent functional pathways. CONCLUSIONS The adult central nervous system reorganizes motor and language areas in patients with glioma. Ultimately, adult neural plasticity may help to preserve motor and language function in the presence of evolving structural lesions. The insight gained from this subset of patients has implications for our understanding of brain plasticity in clinical settings. PMID- 26544768 TI - The GNAQ in the haystack: intramedullary meningeal melanocytoma of intermediate grade at T9-10 in a 58-year-old woman. AB - Meningeal melanocytomas are rare tumors. They are derived from leptomeningeal melanocytes and predominantly occur along the spine and the posterior fossa. Here, the authors report a case of intramedullary melanocytoma of intermediate grade in a 58-year-old female patient who was initially misdiagnosed with malignant melanoma until mutational analyses of a panel of genes associated with melanotic tumors led to reclassification. PMID- 26544770 TI - Retraction: Anatomy of the subthalamic nucleus, with correlation of deep brain stimulation. PMID- 26544769 TI - Graph theory analysis of complex brain networks: new concepts in brain mapping applied to neurosurgery. AB - Neuroanatomy has entered a new era, culminating in the search for the connectome, otherwise known as the brain's wiring diagram. While this approach has led to landmark discoveries in neuroscience, potential neurosurgical applications and collaborations have been lagging. In this article, the authors describe the ideas and concepts behind the connectome and its analysis with graph theory. Following this they then describe how to form a connectome using resting state functional MRI data as an example. Next they highlight selected insights into healthy brain function that have been derived from connectome analysis and illustrate how studies into normal development, cognitive function, and the effects of synthetic lesioning can be relevant to neurosurgery. Finally, they provide a precis of early applications of the connectome and related techniques to traumatic brain injury, functional neurosurgery, and neurooncology. PMID- 26544771 TI - Microfluidics for rapid detection of isocitrate dehydrogenase 1 mutation for intraoperative application. AB - OBJECT Conventional methods for isocitrate dehydrogenase 1 (IDH1) detection, such as DNA sequencing and immunohistochemistry, are time- and labor-consuming and cannot be applied for intraoperative analysis. To develop a new approach for rapid analysis of IDH1 mutation from tiny tumor samples, this study used microfluidics as a method for IDH1 mutation detection. METHODS Forty-seven glioma tumor samples were used; IDH1 mutation status was investigated by immunohistochemistry and DNA sequencing. The microfluidic device was fabricated from polydimethylsiloxane following standard soft lithography. The immunoanalysis was conducted in the microfluidic chip. Fluorescence images of the on-chip microcolumn taken by the charge-coupled device camera were collected as the analytical results readout. Fluorescence signals were analyzed by NIS-Elements software to gather detailed information about the IDH1 concentration in the tissue samples. RESULTS DNA sequencing identified IDH1 R132H mutation in 33 of 47 tumor samples. The fluorescence signal for IDH1-mutant samples was 5.49 +/- 1.87 compared with 3.90 +/- 1.33 for wild type (p = 0.005). Thus, microfluidics was capable of distinguishing IDH1-mutant tumor samples from wild-type samples. When the cutoff value was 4.11, the sensitivity of microfluidics was 87.9% and the specificity was 64.3%. CONCLUSIONS This new approach was capable of analyzing IDH1 mutation status of tiny tissue samples within 30 minutes using intraoperative microsampling. This approach might also be applied for rapid pathological diagnosis of diffuse gliomas, thus guiding personalized resection. PMID- 26544772 TI - Comparison of 7.0- and 3.0-T MRI and MRA in ischemic-type moyamoya disease: preliminary experience. AB - OBJECT The authors compared the image quality and diagnostic sensitivity and specificity of 7.0-T and 3.0-T MRI and time-of-flight (TOF) MR angiography (MRA) in patients with moyamoya disease (MMD). METHODS MR images of 15 patients with ischemic-type MMD (8 males, 7 females; age 13-48 years) and 13 healthy controls (7 males, 6 females; age 19-28 years) who underwent both 7.0-T and 3.0-T MRI and MRA were studied retrospectively. The main intracranial arteries were assessed by using the modified Houkin's grading system (MRA score). Moyamoya vessels (MMVs) were evaluated by 2 grading systems: the MMV quality score and the MMV area score. Two diagnostic criteria for MMD were used: the T2 criteria, which used flow voids in the basal ganglion on T2-weighted images, and the TOF criteria, which used the high-intensity areas in the basal ganglion on source images from TOF MRA. All data were evaluated by 2 independent readers who were blinded to the strength field and presence or absence of MMD. Using conventional angiography as the gold standard, the sensitivity and specificity of 7.0-T and 3.0-T MRI/MRA in the diagnosis of MMD were calculated. The differences between 7.0-T and 3.0-T MRI and MRA were statistically compared. RESULTS No significant differences were observed between 7.0-T and 3.0-T MRA in MRA score (p = 0.317) or MRA grade (p = 0.317). There was a strong correlation between the Suzuki's stage and MRA grade in both 3.0-T (rs = 0.930; p < 0.001) and 7.0-T (rs = 0.966; p < 0.001) MRA. However, MMVs were visualized significantly better on 7.0-T than on 3.0-T MRA, suggested by both the MMV quality score (p = 0.001) and the MMV area score (p = 0.001). The correlation between the Suzuki's stage and the MMV area score was moderate in 3.0-T MRA (rs = 0.738; p = 0.002) and strong in 7.0-T MRA (rs = 0.908; p < 0.001). Moreover, 7.0-T MR images showed a greater capacity for detecting flow voids in the basal ganglion on both T2-weighted MR images (p < 0.001) and TOF source images (p < 0.001); 7.0-T MRA also revealed the subbranches of superficial temporal arteries much better. Receiver operating characteristic curve analysis showed that, according to the T2 criteria, 7.0-T MRI/MRA was more sensitive (sensitivity 1.000; specificity 0.933) than 3.0-T MRI/MRA (sensitivity 0.692; specificity 0.933) in diagnosing MMD; based on the TOF criteria, 7.0-T MRI/MRA was more sensitive (1.000 vs 0.733, respectively) and more specific (1.000 vs 0.923, respectively) than 3.0-T MRI/MRA. CONCLUSIONS Compared with 3.0 T MRI/MRA, 7.0-T MRI/MRA detected and delineated MMVs more clearly and provided higher diagnostic sensitivity and specificity, although it did not show significant improvement in depicting main intracranial arteries. The authors speculate that 7.0-T MRI/MRA is a promising technique in the diagnosis of MMD because it is noninvasive compared with conventional angiography and it is more sensitive than 3.0-T MRI/MRA. PMID- 26544773 TI - Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma. AB - OBJECT This study investigated the role and prognostic value of heat shock proteins (HSPs) in glioma. METHODS Data from 3 large databases of glioma samples (Chinese Glioma Genome Atlas, Repository for Molecular Brain Neoplasia Data, and GSE16011), which contained whole-genome messenger RNA microarray expression data and patients' clinical data, were analyzed. Immunohistochemical analysis was performed to validate protein expression in another set of 50 glioma specimens. RESULTS Of 28 HSPs, 11 were overexpressed in high-grade glioma (HGG) compared with low-grade glioma. A univariate Cox analysis revealed that HSPB11 has significant prognostic value for each glioma grade, which was validated by a Kaplan-Meier survival analysis. HSPB11 expression was associated with poor prognosis and was independently correlated with overall survival (OS) in HGG. This study further explored the combined role of HSPB11 and other molecular markers in HGG, such as isocitrate dehydrogenase 1 (IDH1) mutation and O(6) methylguanine-DNA methyltransferase (MGMT) promoter methylation status. HSPB11 expression was able to refine the prognostic value of IDH1 mutation in patients with HGG. However, when combined with MGMT promoter methylation status, among patients with a methylated MGMT promoter, those with lower levels of HSPB11 expression had longer OS and progression-free survival than patients with higher levels of HSPB11 expression or with an unmethylated MGMT promoter. Moreover, within the MGMT promoter methylation group, patients with low levels of HSPB11 expression were more sensitive to combined radiochemotherapy than those with high levels of HSPB11 expression, which may explain why some patients with HGG with a methylated MGMT promoter show tolerance to radiochemotherapy. CONCLUSIONS HSPB11 was identified as a novel prognostic marker in patients with HGG. Together with MGMT promoter methylation status, HSPB11 expression can predict outcome for patients with HGG and identify those who would most benefit from combined radiochemotherapy. PMID- 26544774 TI - The far-lateral approach: destruction of the condyle does not necessarily result in clinically evident craniovertebral junction instability. AB - OBJECT Far-lateral or extreme-lateral approaches to the skull base allow access to the lateral and anterior portion of the lower posterior fossa and foramen magnum. These approaches include a certain extent of resection of the condyle, which potentially results in craniocervical junction instability. However, it is debated what extent of condyle resection is safe and at what extent of condyle resection an occipitocervical fusion should be recommended. The authors reviewed cases of condyle resection/destruction with regard to necessity of occipitocervical fusion. METHODS The authors conducted a retrospective analysis of all patients in whom a far- or extreme-lateral approach including condyle resection of various extents was performed between January 2007 and December 2014. RESULTS Twenty-one consecutive patients who had undergone a unilateral far- or extreme-lateral approach including condyle resection were identified. There were 10 male and 11 female patients with a median age of 61 years (range 22-83 years). The extent of condyle resection was 25% or less in 15 cases, 50% in 1 case, and greater than 75% in 5 cases. None of the patients who underwent condyle resection of 50% or less was placed in a collar postoperatively or developed neck pain. Two of the patients with condyle resection of greater than 75% were placed in a semirigid collar for a period of 3 months postoperatively and remained free of pain after this period. At last follow-up none of the cases showed any clear sign of radiological or clinical instability. CONCLUSIONS The unilateral resection or destruction of the condyle does not necessarily result in craniocervical instability. No evident instability was encountered even in the 5 patients who underwent removal of more than 75% of the condyle. The far- or extreme-lateral approach may be safer than generally accepted with regard to craniocervical instability as generally considered and may not compel fusion in all cases with condylar resection of more than 75%. PMID- 26544775 TI - Preoperative chemotherapy and corticosteroids: independent predictors of cranial surgical-site infections. AB - OBJECT Preoperative corticosteroids and chemotherapy are frequently prescribed for patients undergoing cranial neurosurgery but may pose a risk of postoperative infection. Postoperative surgical-site infections (SSIs) have significant morbidity and mortality, dramatically increase the length and cost of hospitalization, and are a major cause of 30-day readmission. In patients undergoing cranial neurosurgery, there is a lack of data on the role of patient specific risk factors in the development of SSIs. The authors of this study sought to determine whether chemotherapy and prolonged steroid use before surgery increase the risk of an SSI at postoperative Day 30. METHODS Using the national prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for 2006-2012, the authors calculated the rates of superficial, deep-incisional, and organ-space SSIs at postoperative Day 30 for neurosurgery patients who had undergone chemotherapy or had significant steroid use within 30 days before undergoing cranial surgery. Trauma patients, patients younger than 18 years, and patients with a preoperative infection were excluded. Univariate analysis was performed for 25 variables considered risk factors for superficial and organ-space SSIs. To identify independent predictors of SSIs, the authors then conducted a multivariate analysis in which they controlled for duration of operation, wound class, white blood cell count, and other potential confounders that were significant on the univariate analysis. RESULTS A total of 8215 patients who had undergone cranial surgery were identified. There were 158 SSIs at 30 days (frequency 1.92%), of which 52 were superficial, 27 were deep-incisional, and 79 were organ-space infections. Preoperative chemotherapy was an independent predictor of organ-space SSIs in the multivariate model (OR 5.20, 95% CI 2.33-11.62, p < 0.0001), as was corticosteroid use (OR 1.86, 95% CI 1.03-3.37, p = 0.04), but neither was a predictor of superficial or deep-incisional SSIs. Other independent predictors of organ-space SSIs were longer duration of operation (OR 1.16), wound class of >= 2 (clean-contaminated and further contaminated) (OR 3.17), and morbid obesity (body mass index >= 40 kg/m(2)) (OR 3.05). Among superficial SSIs, wound class of 3 (contaminated) (OR 6.89), operative duration (OR 1.13), and infratentorial surgical approach (OR 2.20) were predictors. CONCLUSIONS Preoperative chemotherapy and corticosteroid use are independent predictors of organ-space SSIs, even when data are controlled for leukopenia. This indicates that the disease process in organ-space SSIs may differ from that in superficial SSIs. In effect, this study provides one of the largest analyses of risk factors for SSIs after cranial surgery. The results suggest that, in certain circumstances, modulation of preoperative chemotherapy or steroid regimens may reduce the risk of organ-space SSIs and should be considered in the preoperative care of this population. Future studies are needed to determine optimal timing and dosing of these medications. PMID- 26544776 TI - Age-related outcomes following intracranial aneurysm treatment with the Pipeline Embolization Device: a subgroup analysis of the IntrePED registry. AB - OBJECT The association between age and outcomes following aneurysm treatment with flow diverters such as the Pipeline Embolization Device (PED) have not been well established. Using the International Retrospective Study of the Pipeline Embolization Device (IntrePED) registry, the authors assessed the age-related clinical outcomes of patients undergoing aneurysm embolization with the PED. METHODS Patients with unruptured aneurysms in the IntrePED registry were divided into 4 age groups: <= 50, 51-60, 61-70, and > 70 years old. The rates of the following postoperative complications were compared between age groups using chi square tests: spontaneous rupture, intracranial hemorrhage (ICH), ischemic stroke, parent artery stenosis, cranial neuropathy, neurological morbidity, neurological mortality, combined neurological morbidity and mortality, and all cause mortality. The association between age and these complications was tested in a multivariate logistic regression analysis adjusted for sex, number of PEDs, and aneurysm size, location, and type. RESULTS Seven hundred eleven patients with 820 unruptured aneurysms were included in this study. Univariate analysis demonstrated no significant difference in ICH rates across age groups (lowest 1.0% for patients <= 50 years old and highest 5.0% for patients > 70 years old, p = 0.097). There was no difference in ischemic stroke rates (lowest 3.6% for patients <= 50 years old and highest 6.0% for patients 50-60 years old, p = 0.73). Age > 70 years old was associated with higher rates of neurological mortality; patients > 70 years old had neurological mortality rates of 7.4% compared with 3.3% for patients 61-70 years old, 2.7% for patients 51-60 years old, and 0.5% for patients <= 50 years old (p = 0.006). On multivariate logistic regression analysis, increasing age was associated with higher odds of combined neurological morbidity and mortality (odds ratio 1.02, 95% confidence interval 1.00-1.05; p = 0.03). CONCLUSIONS Increasing age is associated with higher neurological morbidity and mortality after Pipeline embolization of intracranial aneurysms. However, the overall complication rates of PED treatment in this group of highly selected elderly patients (> 70 years) were acceptably low, suggesting that age alone should not be considered an exclusion criterion when considering treatment of intracranial aneurysms with the PED. PMID- 26544777 TI - Intraarterial administration of norcantharidin attenuates ischemic stroke damage in rodents when given at the time of reperfusion: novel uses of endovascular capabilities. AB - OBJECT Matrix metalloprotease-9 (MMP-9) plays a critical role in infarct progression, blood-brain barrier (BBB) disruption, and vasogenic edema. While systemic administration of MMP-9 inhibitors has shown neuroprotective promise in ischemic stroke, there has been little effort to incorporate these drugs into endovascular modalities. By modifying the rodent middle cerebral artery occlusion (MCAO) model to allow local intraarterial delivery of drugs, one has the ability to mimic endovascular delivery of therapeutics. Using this model, the authors sought to maximize the protective potential of MMP-9 inhibition by intraarterial administration of an MMP-9 inhibitor, norcantharidin (NCTD). METHODS Spontaneously hypertensive rats were subjected to 90-minute MCAO followed immediately by local intraarterial administration of NCTD. The rats' neurobehavioral performances were scored according to the ladder rung walking test results and the Garcia neurological test for as long as 7 days after stroke. MRI was also conducted 24 hours after the stroke to assess infarct volume and BBB disruption. At the end of the experimental protocol, rat brains were used for active MMP-9 immunohistochemical analysis to assess the degree of MMP-9 inhibition. RESULTS NCTD-treated rats showed significantly better neurobehavioral scores for all days tested. MR images also depicted significantly decreased infarct volumes and BBB disruption 24 hours after stroke. Inhibition of MMP-9 expression in the ischemic region was depicted on immunohistochemical analysis, wherein treated rats showed decreased active MMP-9 staining compared with controls. CONCLUSIONS Intraarterial NCTD significantly improved outcome when administered at the time of reperfusion in a spontaneously hypertensive rat stroke model. This study suggests that supplementing endovascular revascularization with local neuroprotective drug therapy may be a viable therapeutic strategy. PMID- 26544778 TI - Calvarial slope affecting accuracy of Ghajar Guide technique for ventricular catheter placement. AB - OBJECT The Ghajar Guide technique is used to direct a ventricular catheter at a 90 degrees angle to the skull surface at Kocher's point. However, the human calvaria is not completely spherical. Lateral to the sagittal midline, the calvaria slopes downward with individual variation and thereby affects the accuracy of ventricular catheter placement. Accordingly, the authors investigated the accuracy of the orthogonal catheter trajectory using radiographic simulation and examined the effect of the calvarial slope on this accuracy. METHODS A catheter trajectory orthogonal to the skull surface at Kocher's point and the ideal catheter trajectory to the foramen of Monro were drawn bilaterally on coronal head images of 52 patients with hydrocephalus. The correction angle, the difference between the 2 catheter trajectories, was then measured. Meanwhile, the calvarial slope was measured around Kocher's point by using a coronal head image. The correlation between the correction angle and factors such as the calvarial slope and bicaudate index was then assessed using a Pearson correlation analysis. RESULTS The ventricular catheter trajectory orthogonal to the skull at Kocher's point in the patients with hydrocephalus led to a catheter trajectory into the ipsilateral (70.2%) or contralateral (29.8%) lateral ventricles. The correction angles ranged from -3.3 degrees to 16.4 degrees (mean +/- SD 5.7 degrees +/- 3.7 degrees ). In 87 (83.7%) head sides, lateral deviation from the orthogonal trajectory was required to approximate the ideal trajectory, and the correction angle ranged from 2.0 degrees to 16.4 degrees (mean 6.7 degrees +/- 2.9 degrees ). The calvarial slope in the 104 head sides ranged from 15.6 degrees to 32.5 degrees (mean 24.2 degrees +/- 3.1 degrees ). Pearson correlation analysis revealed a strong positive correlation (r = 0.733) between the calvarial slope and the correction angle. CONCLUSIONS The accuracy of ventricular catheter placement using the Ghajar Guide technique is affected primarily by the calvarial slope around Kocher's point. A radiographic analysis of a preoperative coronal head image can be used to estimate the accuracy of ventricular catheter placement and enable adjustment to approximate the ideal catheter trajectory. PMID- 26544779 TI - Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3. AB - OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents. PMID- 26544780 TI - Letter to the Editor: Vascularized rotational temporal bone flap. PMID- 26544781 TI - A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas. AB - OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4 point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence. PMID- 26544782 TI - Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? AB - OBJECT Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases. METHODS A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received. RESULTS The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06 5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18-0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT. CONCLUSIONS Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era. PMID- 26544783 TI - Does Sexting Improve Adult Sexual Relationships? PMID- 26544786 TI - Correction to: Cyberpsychol Behav Soc Netw 2015;18(2);59-71 DOI: 10.1089/cyber.2014.0343. AB - In the February 2015 issue of Cyberpsychology, Behavior, and Social Networking (vol. 18, no. 2, pp. 59-71), the article "Association Between Pornography Use and Sexual Risk Behaviors in Adult Consumers: A Systematic Review," by Emily L. Harkness et al., the second author's name was displayed as "Barbara M. Mullan;" however, the middle initial is incorrect. The authors wish to apologize for the error and Dr. Mullan would like to be cited without a middle initial simply as "B Mullan." PMID- 26544787 TI - 3-month triptorelin in premenopausal patients with hormone receptor-positive early breast cancer: a commentary and a retrospective experience. PMID- 26544788 TI - Protective effect of naringin on 3-nitropropionic acid-induced neurodegeneration through the modulation of matrix metalloproteinases and glial fibrillary acidic protein. AB - Naringin (4',5,7-trihydroxy-flavonone-7-rhamnoglucoside), a flavonone present in grapefruit, has recently been reported to protect against neurodegeration, induced with 3-nitropropionic acid (3-NP), through its antioxidant, anti inflammatory, and antiapoptotic properties. This study used a rat model of 3-NP induced neurodegeneration to investigate the neuroprotective effects of naringin exerted by modulating the expression of matrix metalloproteinases and glial fibrillary acidic protein. Neurodegeneration was induced with 3-NP (10 mg/kg body mass, by intraperitoneal injection) once a day for 2 weeks, and induced rats were treated with naringin (80 mg/kg body mass, by oral gavage, once a day for 2 weeks). Naringin ameliorated the motor abnormalities caused by 3-NP, and reduced blood-brain barrier dysfunction by decreasing the expression of matrix metalloproteinases 2 and 9, along with increasing the expression of the tissue inhibitors of metalloproteinases 1 and 2 in 3-NP-induced rats. Further, naringin reduced 3-NP-induced neuroinflammation by decreasing the expression of nuclear factor-kappa B and glial fibrillary acidic protein. Thus, naringin exerts protective effects against 3-NP-induced neurodegeneration by ameliorating the expressions of matrix metalloproteinases and glial fibrillary acidic protein. PMID- 26544789 TI - Hypofractionated Radiotherapy for Children With Diffuse Intrinsic Pontine Gliomas. AB - Children with diffuse intrinsic pontine gliomas have very poor outcomes, with nearly all children dying from disease. Standard therapy includes 6 weeks of radiation. There have been descriptions of using a shortened course of radiation. We describe our experience with a hypofractionated radiotherapy approach delivered over five treatments. In seven children, hypofractionated radiotherapy was well tolerated, but symptomatic radiation necrosis was seen in three of the children. Overall survival was slightly shorter than previously described in the literature. We are developing a prospective dose-finding protocol with the goal of tolerable short-course radiation treatment with outcomes comparable to conventional radiation. PMID- 26544790 TI - Automated Perimetry Under the Microscope: A Re-Examination of Fundamental Assumptions. PMID- 26544791 TI - Phenotypic Change and Induction of Cytokeratin Expression During In Vitro Culture of Corneal Stromal Cells. AB - PURPOSE: Cells of the corneal epithelium and stroma can be distinguished in vivo by different intermediate filaments, cytokeratins for corneal epithelial cells (CEC) and vimentin for keratocytes. Isolated and cultured keratocytes change phenotype, losing expression of keratocyte markers and gaining markers associated with mesenchymal stromal cells (MSC). This study investigates this change in phenotype in relation to intermediate filament expression in cultured corneal stromal cells (CSC) compared to CEC. METHODS: Expression of epithelial markers (CK3, CK12, CK19, pan cytokeratin, E-cadherin), keratocyte markers (CD34, vimentin), and MSC markers (CD73, CD90, and CD105) were compared in CEC and CSC by immunocytochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Expression was evaluated at different stages of CSC culture and compared to another stromal cell type, extracted from Wharton's jelly (WJ MSC). RESULTS: In vivo keratocytes did not express cytokeratins. However, cultured CSC expressed epithelial-associated CK3, CK12, and CK19, but not other cytokeratins. Expression of cytokeratins increased as CSC were passaged and decreased as CSC were induced to become quiescent. Comparatively, WJ-MSC expressed lower levels of CK3, CK12, and CK19, but also stained for pan cytokeratin and expressed KRT5. CONCLUSIONS: Cultured CSC undergo phenotypic change during culture, expressing specific cytokeratin filaments normally associated with CEC. Cytokeratin expression begins as cells are cultured on plastic and increases with passage. This discovery may influence the way in which differences are discerned between cultured CEC and CSC. Investigators need to be aware that the expression of cytokeratins does not necessarily represent epithelial contamination, and that CEC and CSC may be more related than previously recognized. PMID- 26544792 TI - Pathologic Changes of Cone Photoreceptors in Eyes With Occult Macular Dystrophy. AB - PURPOSE: Occult macular dystrophy (OMD) is an inherited retinal disease characterized by a progressive decrease of vision and appearance of normal fundus. To determine the pathologic features of OMD, we investigated the alternation of the photoreceptors using quantitative image analysis. METHODS: We studied 22 eyes of 11 OMD patients. Three of them had a mutation (R45W) in RP1L1. The relative intensities of the ellipsoid zone in the spectral-domain optical coherence tomography (SD-OCT) images and the density of the cone photoreceptors in the adaptive optics (AO) fundus images of the OMD patients were compared to those of normal controls. RESULTS: The relative intensities of the ellipsoid zone in the SD-OCT images of patients with OMD were significantly lower (P < 0.001) by an average of 16% compared to that of the normal controls. Normal cone mosaics were not observed in the AO images of the macula in the eyes with OMD. The mean +/- SD of cone density of the 9 OMD patients was 1970 +/- 884 cells/mm2 at 2 degrees , 1124 +/- 483 cells/mm2 at 3 degrees , and 1288 +/- 715 cells/mm2 at 4 degrees nasal to the fovea. The cone densities at 2 degrees , 3 degrees , and 4 degrees nasal to the fovea of OMD were significantly lower than those of the normal controls (P < 0.001). CONCLUSIONS: A sparse array of cone photoreceptors with significantly reduced density of the macula is one of the morphologic features of OMD. PMID- 26544793 TI - Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea. AB - PURPOSE: We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. METHODS: Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or IFN-gamma stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned media (CoM). Corneal endothelial viability was tested by nuclear counting, connexin 43, and propidium iodide staining. Chemokine and chemokine receptor expression in monocytes and MDMs was assessed in microarray transcriptomic data. The role of chemokine pathways in monocyte migration across microvascular endothelium was tested in vitro by chemokine depletion or chemokine receptor inhibitors. RESULTS: Inflammatory monocytes were significantly enriched in anterior chamber samples within 1 week of the onset of symptoms of corneal graft rejection. The MDM inflammatory CoM was cytopathic to transformed human corneal endothelia. This effect was also evident in endothelium of excised human cornea and increased in the presence of monocytes. Gene expression microarrays identified monocyte chemokine receptors and cognate chemokines in MDM inflammatory responses, which were also enriched in anterior chamber samples. Depletion of selected chemokines in MDM inflammatory CoM had no effect on monocyte transmigration across an endothelial blood-eye barrier, but selective chemokine receptor inhibition reduced monocyte recruitment significantly. CONCLUSIONS: We propose a role for inflammatory monocytes in endothelial cytotoxicity in corneal graft rejection. Therefore, targeting monocyte recruitment offers a putative novel strategy to reduce donor endothelial cell injury in survival of human corneal allografts. PMID- 26544794 TI - Automated Tear Film Surface Quality Breakup Time as a Novel Clinical Marker for Tear Hyperosmolarity in Dry Eye Disease. AB - PURPOSE: To assess the diagnostic performance of a novel, automated, noninvasive measure of tear film stability derived from Placido disc videokeratography, the tear film surface quality breakup time (TFSQ-BUT), as a clinical marker for diagnosing dry eye disease (DED) relative to a standard of tear hyperosmolarity. METHODS: This prospective, cross-sectional study involved 45 participants (28 DED, 17 controls). Symptoms (Ocular Surface Disease Index) and signs (tear osmolarity, TFSQ-BUT, tear breakup time measured with sodium fluorescein [NaFl BUT], ocular surface staining and Schirmer test with topical anesthesia) of DED were assessed. Three measures of TFSQ-BUT and NaFl-BUT were taken per eye; "first," "average," and "shortest" BUT were analyzed separately. Optimal diagnostic cutoff values were determined using the Youden Index. The repeatability and agreement of the TFSQ-BUT was compared with two clinicians who manually assessed noninvasive BUT (CNI-BUT). Repeatability of methods was assessed using the geometric coefficient of variation (gCoV, %). Agreement between methods was considered with Bland-Altman analysis. RESULTS: Eyes with DED had significantly shorter TFSQ-BUTs than controls (P < 0.05). There was a significant, moderate correlation between both shortest and average TFSQ-BUT and NaFl-BUT (r = 0.35, P = 0.02 and r = 0.38, P = 0.01, respectively). The receiver operator characteristic (ROC) curve for shortest TFSQ-BUT showed an area under the curve of 0.92 (P < 0.0001). Shortest TFSQ-BUT with a criterion of 12.1 seconds had a sensitivity of 82% and specificity of 94% for diagnosing DED against tear hyperosmolarity. Automated TFSQ-BUT showed less variability (gCoV = 9.4%, 95% confidence interval [CI]: 7.1%-14.0%) than CNI-BUT (gCoV = 27.0%, 95% CI: 19.62%-41.06%, P < 0.05). CONCLUSIONS: Automated TFSQ-BUT is a repeatable, noninvasive clinical marker with both high sensitivity and specificity for tear hyperosmolarity. PMID- 26544796 TI - Antidiabetic potential of a peptide isolated from an endophytic Aspergillus awamori. AB - AIM: To exploit the potential of endophytic fungi for pharmaceutically important antidiabetic alpha glycosidase inhibitors. METHODS AND RESULTS: Thirty six endophytic fungi were isolated from Acacia nilotica and screened for the production of alpha amylase and glucosidase inhibitors. Inhibitory activity against both alpha amylase (81%) and alpha glucosidase (80%) was exhibited in an isolate, identified to be Aspergillus awamori. Purification of the inhibitor was carried out on Sephadex LH-20 column and semi prep HPLC. The inhibitor was characterized to be proteinaceous in nature with an approximate molecular mass of 22 kDa. UHPLC amino acid analysis indicated the presence of amino acids serine, threonine, tyrosine and valine in the peptide. The purified inhibitor exhibited mixed type of inhibition against alpha amylase and alpha glucosidase with IC50 values of 3.75 and 5.625 MUg ml(-1) respectively. The inhibitor was stable over a wide range of pH and temperature. Optimization of process parameters to increase the yield of the inhibitor was undertaken using one factor at a time approach as well as RSM statistical analysis. The interaction of dextrose and proteose peptone for the test organism was significant with first order effect of pH. Increase of 13% was obtained in the inhibitory activity after optimization of process parameters. Mutagenicity testing by Ames test revealed nonmutagenic nature of the peptide. CONCLUSION: Endophytic A. awamori is capable of producing a peptide with alpha glycosidase inhibitory activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The inhibitor obtained in this study possesses dual (alpha glucosidase and alpha amylase) inhibitory activity, low IC50 values, is highly stable under extreme conditions of pH and temperature, and is nonmutagenic in nature. By virtue of its properties it can be commercially produced and exploited for better management of diabetes. PMID- 26544795 TI - Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins. AB - In the influenza virus field, antibody reagents from research animals have been instrumental in the characterization of antigenically distinct hemagglutinin and neuraminidase membrane molecules. These small animal reagents continue to support the selection of components for inclusion in human influenza virus vaccines. Other cocktail vaccines against variant pathogens (e.g., polio virus, pneumococcus) are similarly designed to represent variant antigens, as defined by antibody reactivity patterns. However, a vaccine cocktail comprising diverse viral membrane antigens defined in this way has not yet been advanced to a clinical efficacy study in the HIV-1 field. In this study, we describe the preparation of mouse antibodies specific for HIV-1 gp140 or gp120 envelope molecules. Our experiments generated renewable reagents able to discriminate HIV 1 envelopes from one another. Monoclonals yielded more precise discriminatory capacity against their respective immunogens than did a small panel of polyclonal human sera derived from recently HIV-1-infected patients. Perhaps these and other antibody reagents will ultimately support high-throughput cartography studies with which antigenically-distinct envelope immunogens may be formulated into a successful HIV-1 envelope cocktail vaccine. PMID- 26544797 TI - Early changes in extracellular matrix in Alzheimer's disease. AB - AIMS: Although changes in extracellular matrix (ECM) scaffold have been reported previously in Alzheimer's disease (AD) compared to normal ageing, it is not known how alterations in the numerous components of the perivascular ECM might occur at different stages of AD. This study therefore investigates potential changes in basement membrane-associated ECM molecules in relation to increasing Braak stages. METHODS: Thirty patients were divided into three groups (control subject, subclinical AD and AD patients). ECM levels of collagen IV, perlecan and fibronectin as well as human platelet endothelial cell adhesion molecule (hPECAM) were quantified by immunohistochemistry. Von Willebrand factor staining was measured to assess vessel density. Expression levels were correlated with the presence of amyloid plaques. RESULTS: Collagen IV, perlecan and fibronectin expression was increased in subclinical AD and AD patients when compared to controls, in frontal and temporal cortex, whilst no further increase was detected between subclinical AD and AD. These changes were not associated with an increase in vessel density, which was instead decreased in the temporal cortex of AD patients. In contrast, hPECAM levels remained unchanged. Finally, we found similar pattern in levels of amyloid deposition between the different Braak stages and showed that changes in ECM components correlated with amyloid deposition. CONCLUSION: Present data support the hypothesis that significant ECM changes occur during the early stages of AD. ECM changes affecting brain microvascular functions could therefore drive disease progression and provide potential new early investigational biomarkers in AD. PMID- 26544798 TI - Screening for nasopharyngeal cancer. AB - BACKGROUND: Nasopharyngeal cancer is endemic in a few well-defined populations. The prognosis for advanced nasopharyngeal cancer is poor, but early-stage disease is curable and a high survival rate can be achieved. Screening for early-stage disease could lead to improved outcomes. Epstein-Barr virus (EBV) serology and nasopharyngoscopy are most commonly used for screening. The efficacy and true benefit of screening remain uncertain due to potential selection, lead-time and length-time biases. OBJECTIVES: To determine the effectiveness of screening of asymptomatic individuals by EBV serology and/or nasopharyngoscopy in reducing the mortality of nasopharyngeal cancer compared to no screening. To assess the impact of screening for nasopharyngeal cancer on incidence, survival, adverse effects, cost-effectiveness and quality of life. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 6 July 2015. SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating screening for nasopharyngeal cancer versus no screening. Randomisation either by clusters or individuals was acceptable. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. Our primary outcome measure was nasopharyngeal cancer-specific mortality. Secondary outcomes were incidence of nasopharyngeal cancer by stage and histopathological classification at diagnosis, survival (two-year, three-year, five-year and 10-year), harms of screening (physical and psychosocial), quality of life (via validated tools such as the SF-36 and patient satisfaction), cost-effectiveness and all-cause mortality. MAIN RESULTS: We identified no trials that met the review inclusion criteria. We retrieved 31 full-text studies for further investigation following the search. However, none met the eligibility criteria for a RCT or CCT investigation on the efficacy of screening for nasopharyngeal cancer. AUTHORS' CONCLUSIONS: No data from RCTs or CCTs are available to allow us to determine the efficacy of screening for nasopharyngeal cancer, or the cost-effectiveness and cost-benefit of a screening strategy. High-quality studies with long-term follow up of mortality and cost-effectiveness are needed. PMID- 26544799 TI - On Receiving the Baton. PMID- 26544803 TI - Two-Variance-Component Model Improves Genetic Prediction in Family Datasets. AB - Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively with best linear unbiased prediction (BLUP) methods. Such methods were pioneered in plant and animal breeding literature and have since been applied to predict human traits, with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two-variance-component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated with genetic markers. In simulations using real genotypes from the Candidate-gene Association Resource (CARe) and Framingham Heart Study (FHS) family cohorts, we demonstrate that the two-variance-component model achieves gains in prediction r(2) over standard BLUP at current sample sizes, and we project, based on simulations, that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two-variance-component model significantly improves prediction r(2) in each case, with up to a 20% relative improvement. We also find that standard mixed-model association tests can produce inflated test statistics in datasets with related individuals, whereas the two-variance component model corrects for inflation. PMID- 26544804 TI - Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome. AB - The genomic duplication associated with Potocki-Lupski syndrome (PTLS) maps in close proximity to the duplication associated with Charcot-Marie-Tooth disease type 1A (CMT1A). PTLS is characterized by hypotonia, failure to thrive, reduced body weight, intellectual disability, and autistic features. CMT1A is a common autosomal dominant distal symmetric peripheral polyneuropathy. The key dosage sensitive genes RAI1 and PMP22 are respectively associated with PTLS and CMT1A. Recurrent duplications accounting for the majority of subjects with these conditions are mediated by nonallelic homologous recombination between distinct low-copy repeat (LCR) substrates. The LCRs flanking a contiguous genomic interval encompassing both RAI1 and PMP22 do not share extensive homology; thus, duplications encompassing both loci are rare and potentially generated by a different mutational mechanism. We characterized genomic rearrangements that simultaneously duplicate PMP22 and RAI1, including nine potential complex genomic rearrangements, in 23 subjects by high-resolution array comparative genomic hybridization and breakpoint junction sequencing. Insertions and microhomologies were found at the breakpoint junctions, suggesting potential replicative mechanisms for rearrangement formation. At the breakpoint junctions of these nonrecurrent rearrangements, enrichment of repetitive DNA sequences was observed, indicating that they might predispose to genomic instability and rearrangement. Clinical evaluation revealed blended PTLS and CMT1A phenotypes with a potential earlier onset of neuropathy. Moreover, additional clinical findings might be observed due to the extra duplicated material included in the rearrangements. Our genomic analysis suggests replicative mechanisms as a predominant mechanism underlying PMP22-RAI1 contiguous gene duplications and provides further evidence supporting the role of complex genomic architecture in genomic instability. PMID- 26544805 TI - Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models. AB - In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (delta(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of delta(2) were evident for 14 traits in twin models (average delta(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant delta(2) in the GREMLd analyses (triglycerides delta(2)SNP = 0.28 and waist circumference delta(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs). PMID- 26544807 TI - Can Large Database Studies Help Us Decrease Readmissions After Colorectal Surgery? PMID- 26544806 TI - Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering. AB - Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of function mutations in this gene. AP4E1 encodes the epsilon subunit of the heterotetrameric (epsilon-beta4-MU4-sigma4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the MU4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6 phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering. PMID- 26544808 TI - Outcomes of Open, Laparoscopic, and Robotic Abdominoperineal Resections in Patients With Rectal Cancer. AB - BACKGROUND: There are limited available data comparing open, laparoscopic, and robotic approaches for rectal cancer surgery. OBJECTIVE: We sought to investigate outcomes of different surgical approaches to abdominoperineal resection in patients with rectal cancer. DESIGN: The nationwide inpatient sample database was used to examine the clinical data of patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012 in the United States. Multivariate regression analysis was performed to compare outcomes of different surgical approaches. SETTINGS: A retrospective review according to the national inpatient sample database was designed. PATIENTS: We included patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012. MAIN OUTCOME MEASURES: Outcomes of different surgical approaches to abdominoperineal resection were investigated. RESULTS: We sampled 18,359 patients with rectal cancer who underwent elective abdominoperineal resections. Of these, 69.5% had open surgery, 25.8% had laparoscopic surgery, and 4.7% had robotic surgery. The rate of robotic procedures increased >4-fold, from 2.1% to 8.1%, from 2009 to 2012. The conversion rate in robotic surgery was significantly lower compared with laparoscopic surgery (5.7% vs 13.4%; p < 0.01). After risk adjustment, patients who underwent laparoscopic and robotic approaches had lower morbidity risks compared with those who underwent the open approach (adjusted OR = 0.77 (95% CI, 0.65-0.92), 0.57 (95% CI, 0.40-0.80); p < 0. 01). There were no significant differences in the morbidity rate of patients who underwent laparoscopic or robotic approaches (adjusted OR = 0.79 (95% CI, 0.55-1.14); p = 0.21). However, patients who underwent the robotic approach had significantly higher total hospital charges compared with those who underwent the laparoscopic approach (mean difference, $24,890; p < 0.01). LIMITATIONS: We could not adjust the results with some important factors, such as the tumor stage and BMI. CONCLUSIONS: The use of robotic and laparoscopic approaches to abdominoperineal resection have increased between 2009 and 2012. Both minimally invasive approaches decrease morbidity rates of patients undergoing abdominoperineal resection. The robotic approach has a significantly lower conversion rate compared with the laparoscopic approach. However, it had significantly higher total hospital charges compared with the laparoscopic approach. PMID- 26544809 TI - HIV Infection Is Associated With Poor Outcomes for Patients With Anal Cancer in the Highly Active Antiretroviral Therapy Era. AB - BACKGROUND: HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. OBJECTIVE: Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV negative patients with anal cancer. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at an outpatient oncology clinic at large academic center. PATIENTS: A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. MAIN OUTCOME MEASURES: Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. RESULTS: Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. LIMITATIONS: This study was limited by its retrospective design and small patient numbers. CONCLUSIONS: In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of this difference. PMID- 26544810 TI - Features Associated With Metastases Among Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Appendix: The Significance of Small Vessel Invasion in Addition to Size. AB - BACKGROUND: The risk of metastatic disease among carcinoid tumors of the appendix increases with tumor size. However, it is unclear if any features other than size are also associated with an increased risk of metastatic disease. OBJECTIVE: The aim of this study was to review the characteristics of appendiceal carcinoid tumors and determine if other histologic features besides size should guide surgical decision making. DESIGN: This study involved a retrospective case series. SETTINGS: This study was conducted at a single tertiary acute care hospital. PATIENTS: Patients diagnosed with an appendiceal carcinoid tumor between 2000 and 2014 were identified. Goblet cell carcinoids, adenocarcinomas with neuroendocrine features, and tumors from other primary locations were excluded. INTERVENTIONS: Simple appendectomy or segmental/total colectomy with lymphadenectomy was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were metastases, recurrence, and overall survival. RESULTS: Seventy-nine patients were included. The overall incidence of metastatic disease was 10%. Patients with metastatic disease were more likely to be male (75% vs 28%, p = 0.008), have small-vessel invasion (43% vs 5%, p = 0.001), and have larger tumors (median 2.0 cm vs 0.5 cm, p < 0.001). Among tumors <2 cm, the incidence of metastases among tumors with small-vessel invasion was 60% compared with 0% among those without small-vessel invasion (p < 0.001). Among tumors >=2 cm, the incidence of metastases was 50% irrespective of small-vessel invasion. If small vessel invasion was used as a second indication for performing a right hemicolectomy along with size >=2 cm, both the sensitivity and negative predictive value would have been 100% compared with 63% and 96% if size was used alone. Patients with metastatic disease had a higher incidence of recurrence (13% vs 0%, p = 0.003), but overall survival was 100% in both groups. LIMITATIONS: Small sample size, retrospective design, and limited long-term follow-up were the limitations of this study. CONCLUSIONS: Carcinoid tumors of the appendix <2 cm with small-vessel invasion have similar metastatic potential as tumors >=2 cm. Therefore, a recommendation for a right hemicolectomy should be considered for tumors <2 cm with small-vessel invasion. Additional prospective multicenter studies are warranted. PMID- 26544811 TI - Impact of Surgery on Relationship Quality in Patients With Ulcerative Colitis and Their Partners. AB - BACKGROUND: Although social support is important for quality of life in patients undergoing surgery for ulcerative colitis, the impact of surgery on patient relationships is not known. OBJECTIVE: We examined relationship parameters in patients with ulcerative colitis and their partners before and 6 months after surgery. DESIGN: This was a prospective cohort in which we performed an exploratory analysis. SETTINGS: Patients were enrolled from an academic medical center. PATIENTS: Surgical patients with ulcerative colitis and their partners were invited to participate. INTERVENTIONS: Patients underwent proctocolectomy in 1, 2, or 3 stages. MAIN OUTCOME MEASURES: We measured quality of life and sexual function in patients, as well as relationship quality, empathy, and sexual satisfaction in patients and partners before and 6 months after surgery using validated questionnaires. RESULTS: The study sample consisted of 74 participants, including 37 patients (25 men and 12 women) and their opposite-sex partners. Quality of life improved significantly in male and female patients after surgery. Sexual function scores also improved after surgery in male and female patients; however, the changes reached statistical significance in male patients only. Sexual satisfaction scores improved significantly after surgery in female patients and their partners. There was little change in relationship quality or empathy after surgery, with the exception of slightly improved relationship quality reported by male partners. In general, patients and partners reported levels of relationship quality and empathy similar to normative populations. LIMITATIONS: This study included a small, highly selected sample. CONCLUSIONS: Male and female patients with ulcerative colitis have high-quality relationships that are not negatively affected by surgical treatment. Changes in sexual function do not necessarily coincide with changes in sexual satisfaction in this patient population. Future studies should evaluate the effect of high-quality relationships on surgical outcomes. PMID- 26544812 TI - Clinical Outcomes of Surgery Versus Endoscopic Balloon Dilation for Stricturing Crohn's Disease. AB - BACKGROUND: Endoscopic balloon dilation and surgery are commonly practiced in stricturing Crohn's disease. Nonetheless, there are still scant data directly comparing these 2 strategies. OBJECTIVE: The aim of this study was to compare the short- and long-term outcomes of endoscopic balloon dilation versus surgical resection in symptomatic Crohn's strictures. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary center. PATIENTS: Seventy-nine patients were identified, 40 in the surgical group and 39 in the endoscopic balloon dilation group (mean age 42.8 +/- 13.9 versus 38.5 +/- 12.2 years). MAIN OUTCOME MEASURES: The outcomes of all patients referred for endoscopic balloon dilation were compared with patients referred to surgery because of stricturing disease between the years 2006 and 2013. The primary outcome was the need for reintervention (either endoscopic balloon dilation or surgery) for symptomatic Crohn's disease during follow-up. RESULTS: The proportion of patients who required any reintervention during follow-up was significantly lower in the surgical group versus the endoscopic balloon dilation group (OR = 5.62 (95% CI, 1.66-19.01); p = 0.005). The need for surgery/resurgery during follow-up was also significantly lower in the surgically treated group (OR = 3.53 (95% CI, 1.01-12.29); p = 0.047). Reintervention-free survival and surgery free survival were both significantly shorter in the endoscopically treated group in a Kaplan-Mayer analysis. The rate of major complications was similar in the endoscopically and surgically treated groups (7.6% versus 7.5%; p = 0.7). LIMITATIONS: The small cohort and the retrospective data collection were limitations of this study. CONCLUSIONS: In our cohort of patients with fibrostenotic Crohn's disease, a direct comparison showed reduced need for reinterventions with a similar rate of immediate major complications after surgery compared with endoscopic balloon dilation. PMID- 26544813 TI - Does Stool Leakage Increase in Aging Pouches? AB - BACKGROUND: Restorative proctocolectomy with IPAA is the standard surgical option for patients with ulcerative colitis. Although ileal pouches have been shown to have acceptable functional outcomes, some patients experience fecal incontinence. OBJECTIVE: The purpose of this study was to evaluate the incidence of fecal leakage and the way it may change over time in patients with an ileoanal pouch. DESIGN: This study used a retrospective design. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: Patients who received an IPAA for ulcerative colitis between 1983 and 2008 were accessed from a prospectively maintained database. We excluded patients with cancer, colonic dysplasia, and missing record of ileostomy closure and without long-term functional data. MAIN OUTCOME MEASURES: We defined fecal leakage as leakage of stool more than once per day. Univariate and multivariate analyses were performed to identify associations with and possible risk factors for fecal leakage. RESULTS: A total of 1228 patients were included in this study. There were 656 men, with a mean age of 38.7 years. The median follow-up time was 158 months. The fecal leakage rates at 5, 10, and >15 years were 24.6%, 25.7%, and 27.4% (p = 0.66). Patients with fecal leakage were significantly older at the time of surgery (p < 0.001), had longer disease duration before surgery (p = 0.04), underwent more 2-stage surgery (p = 0.04), included more women (p < 0.01), and showed lower preoperative maximum anal squeeze pressure (p = 0.008). On multivariate analysis, the only significant factor predisposing to fecal leakage was older age at the time of pouch surgery (OR = 1.07 (95% CI, 1.02-1.12); p = 0.005). LIMITATIONS: The study was limited by its retrospective and non-randomized nature. CONCLUSIONS: The occurrence of fecal leakage in patients with IPAA does not change with time. However, increased age at the time of surgery may increase the chances of patients with IPAA having fecal leakage. PMID- 26544814 TI - Readmission After Resections of the Colon and Rectum: Predictors of a Costly and Common Outcome. AB - BACKGROUND: Readmission rates are a measure of surgical quality and an object of clinical and regulatory scrutiny. Despite increasing efforts to improve quality and contain cost, 6% to 25% of patients are readmitted after colorectal surgery. OBJECTIVE: The aim of this study is to define the predictors and costs of readmission following colorectal surgery. DESIGN: This is a retrospective cohort study of patients undergoing elective and nonelective colectomy and/or proctectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007 to 2011. Readmission is defined as inpatient admission within 30 days of discharge. Univariate analyses were performed of sex, age, Elixhauser score, race, insurance type, procedure, indication, readmission diagnosis, cost, and length of stay. Multivariate analysis was performed by logistic regression. Sensitivity analysis of nonemergent admissions was conducted. SETTINGS: This study was conducted in Florida acute-care hospitals. PATIENTS: Patients undergoing colectomy and proctectomy from 2007 to 2011 were included. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The primary outcomes measured were readmission and the cost of readmission. RESULTS: A total of 93,913 patients underwent colectomy; 14.7% were readmitted within 30 days. From 2007 to 2011, readmission rates remained stable (14.6% 14.2%, trend p = 0.1585). After multivariate adjustment, patient factors associated with readmission included nonwhite race, age <65, and a diagnosis code other than neoplasm or diverticular disease (p < 0.0001). Patients with Medicare or Medicaid were more likely to be readmitted than those with private insurance (p < 0.0001). Patients with longer index admissions, those with stomas, and those undergoing all procedures other than sigmoid or transverse colectomy were more likely to be readmitted (p < 0.0001). High-volume hospitals had higher rates of readmission (p < 0.0001). The most common reason for readmission was infection (32.9%). Median cost of readmission care was $7030 (intraquartile range, $4220 $13,247). Fistulas caused the most costly readmissions ($15,174; intraquartile range, $6725-$26,660). LIMITATIONS: Administrative data and retrospective design were limitations of this study. CONCLUSIONS: Readmissions rates after colorectal surgery remain common and costly. Nonprivate insurance, IBD, and high hospital volume are significantly associated with readmission. PMID- 26544815 TI - Characteristics of Colonic Diverticulitis and Factors Associated With Complications: A Japanese Multicenter, Retrospective, Cross-Sectional Study. AB - BACKGROUND: Little is known about the epidemiology of diverticulitis in Japan. Additional information is needed about its clinical characteristics and the factors associated with complications of diverticulitis. OBJECTIVE: This study was designed to determine the clinical characteristics of diverticulitis and factors associated with its complications in Japanese patients. DESIGN: This was a retrospective, multicenter, large-scale, cross-sectional study. SETTINGS: All of the consecutive patients in 21 Japanese hospitals with a final diagnosis of acute colonic diverticulitis were included in this study. PATIENTS: A total of 1112 patients, including 658 men and 454 women, with a mean age of 54.8 years, who were diagnosed by CT and/or ultrasonography between January 2006 and May 2011, were included in this study. INTERVENTIONS: Data on medical history, investigations, treatments, and prognosis were collected using a standard form to create a dedicated database. MAIN OUTCOME MEASURES: Clarification of the clinical characteristics of Japanese patients with acute diverticulitis was the main outcome measured. RESULTS: Diverticulitis was detected mainly in men and women aged 40 to 60 years. Although diverticulitis more frequently affected the right colon (70.1%), diverticulitis of the left colon was significantly more frequent (61.0%) in elderly patients. Of the 1112 patients with diverticulitis, 179 (16.1%) developed complications, including abscess formation, perforation, stenosis, and/or fistula, some of which required surgical treatment, such as drainage or colonic resection. The duration of hospitalization (24.1 +/- 19.5 days) and mortality rate (2.8%) were significantly higher in patients with versus without complications. Factors associated with complications were fever (>38.5 degrees C), involvement of the left colon, higher age, and delayed diagnosis. LIMITATIONS: Limitations included the nonconsideration of diverticulitis treatment, the effect of dietary fiber, and the retrospective design of the study. CONCLUSIONS: Complications were more frequent in elderly men with left sided diverticulitis, although diverticulitis was more common in middle-aged people and on the right side of the colon. Factors associated with complications were fever, site of involvement, older age, and longer time until diagnosis. PMID- 26544816 TI - Dynamic Article: Permanent Sacral Nerve Stimulation Under Local Anesthesia: Feasibility, Best Practice, and Patient Satisfaction. AB - BACKGROUND: The increasing incidence of fecal incontinence and the use of sacral neuromodulation have an increasing impact on health care providers and health care costs. OBJECTIVE: The purpose of this study was to investigate the technical and clinical success rates, complications, and patient satisfaction of the implantation of permanent sacral nerve stimulation under local anesthesia. DESIGN: A cohort analysis of consecutive patients with sacral nerve stimulation for fecal incontinence over a period of 1 year was performed. SETTINGS: This study was conducted at a specialized pelvic floor unit in a tertiary care center. PATIENTS: Sixty-one patients were available for the assessment after 1-year follow-up. MAIN OUTCOME MEASURES: Technical success, procedural time, and complications were noted. Clinical outcome (including Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Gastrointestinal Quality of Life Index were collected prospectively before and after treatment. RESULTS: All procedures were successfully completed under local anesthesia, with a median total procedural time of 50 minutes (range, 26-72 minutes). All patients were discharged on the day of their procedure. Postoperative complications occurred in 3 patients (4.9%). At 3 months follow-up, the median Fecal Incontinence Severity Index score was reduced from 37 to 27 (p = 0.001). Both the Fecal Incontinence Quality of Life scale and the Gastrointestinal Quality of Life Index had improved from 63 to 82 (p < 0.001) and 72 to 90 (p = 0.012). At a mean follow-up of 13 months, both the Fecal Incontinence Quality of Life scale and the Gastrointestinal Quality of Life Index improved further to 90 (p < 0.001) and 94 (p < 0.001). All patients would recommend the procedure under local anesthesia to other patients. No patients experienced leg pain during follow-up. LIMITATIONS: This study involved a relatively small group of patients, and patient satisfaction was only recorded for the last 22 patients. No exact cost calculations were made. CONCLUSIONS: Permanent sacral nerve stimulation implantation under local anesthesia has high technical and clinical success rates. It is safe, well tolerated by patients, and has obvious logistical and financial benefits. PMID- 26544817 TI - Pudendal Neuropathy Alone Results in Urge Incontinence Rather Than in Complete Fecal Incontinence. AB - BACKGROUND: Conscious external anal sphincter contraction is mediated by the pudendal nerve. Pudendal neuropathy is, therefore, believed to result in fecal incontinence. Until urge sensation is experienced, fecal continence is maintained by unconscious external anal sphincter contraction, which is regulated by the anal-external sphincter continence reflex. The innervation of unconscious contraction is yet unknown. OBJECTIVE: We aimed to determine whether unconscious contraction is mediated by the pudendal nerve and whether age influences unconscious contraction. DESIGN: This was a retrospective comparative study. SETTINGS: The study was conducted in a tertiary care center. PATIENTS: Seventy adult patients experiencing defecation problems who underwent anorectal function tests were included in this study. MAIN OUTCOME MEASURES: Conscious and unconscious contractions were compared between patients with and without pudendal neuropathy. Conscious contraction was defined by maximum anal sphincter contractility, unconscious contraction by pressure in the anal canal at maximum tolerable or retainable sensation during the balloon retention test. RESULTS: Unconscious contraction did not differ significantly between patients with pudendal neuropathy and non-pudendal neuropathy patients, whereas conscious contraction was significantly lower in patients with pudendal neuropathy. Multiple linear regression analyses demonstrated that unconscious contraction, in contrast to conscious contraction, was not predicted significantly by age and anal electrosensitivity at 2 cm, which represents pudendal neuropathy. Patients with pudendal neuropathy were significantly older than patients with nonpudendal neuropathy. LIMITATIONS: The pudendal nerve motor latency and EMG tests were not performed. CONCLUSIONS: The pudendal nerve does not mediate unconscious external anal sphincter contraction. Pudendal neuropathy alone, therefore, results in urge incontinence rather than in complete fecal incontinence. Unconscious contraction appears not to be influenced by age. Therefore, most of the elderly patients experience urge incontinence rather than complete fecal incontinence. PMID- 26544818 TI - Fecal Incontinence: Community Prevalence and Associated Factors--A Systematic Review. AB - BACKGROUND: Fecal incontinence is a chronic and debilitating condition with significant health burden. Despite its clinical relevance, the prevalence of fecal incontinence remains inconsistently described. OBJECTIVE: This study aimed to systematically review the literature regarding the prevalence of and factors associated with fecal incontinence among community-dwelling adults. DATA SOURCES: A search of the PubMed, Embase, and Cochrane databases was performed. STUDY SELECTION: Studies that reported the prevalence of fecal incontinence and/or associated factors in a community-based (ie, unselected) adult population were included. Two independent assessors reviewed eligible articles. MAIN OUTCOME MEASURES: Relevant data were extracted from each study and presented in descriptive form. The main outcome measures included the prevalence of fecal incontinence (adjusted and/or unadjusted), stratified for age and sex if reported; factors associated (and not associated) with fecal incontinence; and study quality, assessed using predefined criteria. RESULTS: Of 3523 citations identified, 38 studies were included for review. The reported median prevalence of fecal incontinence was 7.7% (range, 2.0%-20.7%). Fecal incontinence equally affected both men (median, 8.1%; range, 2.3%-16.1%) and women (median, 8.9%; range, 2.0%-20.7%) and increased with age (15-34 years, 5.7%; >90 years, 15.9%). The study populations and diagnostic criteria used were heterogeneous, precluding any meaningful pooling of prevalence estimates. Study quality assessment revealed 6 high-quality studies, of which only 3 were performed in a representative sample. The median prevalence of fecal incontinence was higher in these studies at 11.2% (range, 8.3%-13.2%). The factors most commonly reported to be associated with fecal incontinence included increasing age, diarrhea, and urinary incontinence. LIMITATIONS: Heterogeneity of studies precluded meaningful pooling or meta-analysis of data. CONCLUSIONS: Fecal incontinence is a prevalent condition of equal sex distribution, affecting ~1 in 8 community adults, and has identifiable associated factors. The paucity of high-quality prevalence studies emphasizes the need for future population-based studies that use standardized diagnostic criteria for fecal incontinence. PMID- 26544819 TI - Martius Flap for Repair of Recurrent Rectovaginal Fistulas. PMID- 26544820 TI - Why the Conventional Parks Transanal Excision for Early Stage Rectal Cancer Should Be Abandoned. PMID- 26544821 TI - Should a Surgical Approach for an Antegrade Colonic Enema Procedure Be Abandoned in Favor of a CT-Guided Percutaneous Placement of an Indwelling Chait Cecostomy Catheter? PMID- 26544822 TI - The Authors Reply. PMID- 26544823 TI - Bio-Thiersch May Have No Benefit Compared With Absorbable Thiersch Suture When Combined With Perineal Proctectomy. PMID- 26544824 TI - The Author Replies. PMID- 26544825 TI - Ethics in Animal Research: Explicit Explanation Is Necessary. PMID- 26544826 TI - The Authors Reply. PMID- 26544827 TI - Have We Forgotten the Most Important Tenet of Oncologic Surgery? PMID- 26544828 TI - The Authors Reply. PMID- 26544829 TI - Silver Nitrate for Anal Fistulas: A Word of Caution. PMID- 26544830 TI - The Authors Reply. PMID- 26544834 TI - Pressure-Stimulated Synthesis and Luminescence Properties of Microcrystalline (Lu,Y)3Al5O12:Ce3+ Garnet Phosphors. AB - The Lu2.98Ce0.01Y0.01Al5O12 and Y2.99Ce0.01Al5O12 phosphors were synthesized by solid state reaction at temperature 1623 K and pressure 1.5 * 10(7) Pa in (95% N2 + 5% H2) atmosphere. Under the conditions, the compounds crystallize in the form of isolated euhedral partly faceted microcrystals ~19 MUm in size. The crystal structures of the Lu2.98Ce0.01Y0.01Al5O12 and Y2.99Ce0.01Al5O12 garnets have been obtained by Rietveld analysis. The photoluminescence (PL) and X-ray excited luminescence (XL) spectra obtained at room temperature indicate broad asymmetric bands with maxima near 519 and 540 nm for Y2.99Ce0.01Al5O12 and Lu2.98Ce0.01Y0.01Al5O12, respectively. The light source was fabricated using the powder Lu2.98Ce0.01Y0.01Al5O12 phosphor and commercial blue-emitting n-UV LED chips (lambda(ex) = 450 nm). It is found that the CIE chromaticity coordinates are (x = 0.388, y = 0.563) with the warm white light emission correlated color temperature (CCT) of 6400 K and good luminous efficiency of 110 lm/W. PMID- 26544835 TI - Violence against women in the Arab world. PMID- 26544836 TI - Violence against wives: a silent suffering in northern Saudi community. AB - BACKGROUND: Violence against women is a worldwide epidemic. It may take different forms depending on history, culture, background, and experiences, but it causes great suffering for women, their families, and the communities in which they live. Despite its high prevalence, no previous studies that have been conducted in Arar, northern area of Kingdom of Saudi Arabia (KSA), addressing this issue could be traced. OBJECTIVE: The aim of this study was to measure the prevalence and determinants of violence experienced by ever-married women attending primary health centers in Arar city, Northern Border, KSA. PARTICIPANTS AND METHODS: This study is a cross-sectional study conducted during the period from January to June 2014 in Arar city in the Northern Province of the KSA. Data were collected through an interviewer-administered questionnaire. A total of 208 wives (184 currently married, 16 divorced, and eight widowed) attending five randomly selected primary healthcare centers in Arar, KSA, were interviewed. Collected data provided information on both physical and emotional violence. RESULTS: The study revealed that the overall prevalence of domestic violence in the studied group was 80.7 and 100.0% for physical and psychological violence, respectively. On studying the reasons for physical violence, half (50%) of the participants reported no clear cause, 19.2% reported failure to adequately care for children (such as cleaning, feeding, and dressing), and 7.8% reported causes related to poor scholastic achievement and couple conflict about appropriate approaches of upbringing of children. Suspicion on wife's fidelity was the most common form of psychological violence (21%). The perpetrator was the husband in 76.9% of cases and the husband's family was the perpetrator in 3.8% of cases. Physical violence was significantly higher during the first 10 years of marriage compared with other durations. University-educated husbands showed significantly lower percentage of physical violence against women compared with those of other educational levels. CONCLUSION AND RECOMMENDATIONS: Violence against women was highly prevalent in Arar city. Inadequate care of children and poor scholastic achievement were the most common reasons of physical violence, whereas financial conflicts and suspicion of wife's fidelity were the most common reasons for psychological violence. We recommend awareness programs aiming at educating current and future couples, and proper training of healthcare providers for assisting cases experiencing violence against women. PMID- 26544837 TI - Sexual harassment against nursing staff in Tanta University Hospitals, Egypt. AB - BACKGROUND: Sexual harassment against nurses is a major workplace problem causing adverse psychological effects and may affect the occupational performance of the nurses. This study aimed to assess the magnitude of this problem, and its characteristics and consequences among the nursing staff in Tanta University Hospitals, Gharbeia Governorate, Egypt. PARTICIPANTS AND METHODS: A descriptive cross-sectional study was carried out on 430 nurses at Tanta University Hospitals using a semistructured, self-administered questionnaire to collect the data concerning the exposure and characteristics of harassment situations. A representative sample of the nurses was taken randomly from the emergency, medical and surgical departments. RESULTS: Overall, 70.2% of the studied nurses were ever exposed to sexual harassment at the workplace; 43.7% of the harassed nurses were working in both day and night shifts. Staring in a suggestive manner emerged as the most common form of harassment, followed by hearing sexual words and comments or jokes (70.9, 58.6 and 57.3%, respectively). The relatives of the patients were the most common perpetrators, followed by the hospital staff other than the doctors (61.9, 45.4%, respectively). During the harassment situation, astonishment and shock were the most frequent responses in 65.2% of the harassed nurses, while after its occurrence 38.4% ignored the situation. About 95% of the harassed nurses were left with psychological effects, mostly in the form of disappointment and depression (76.5 and 67.9%, respectively). CONCLUSION AND RECOMMENDATIONS: The prevalence of sexual harassment among nurses at the workplace was high with relation to certain occupational factors, and it led to marked psychological effects on the victims. Hence, protective legislations and measures should be taken by the hospital management for prevention of this problem in the future. PMID- 26544838 TI - Screening for antepartum anxiety and depression and their association with domestic violence among Egyptian pregnant women. AB - BACKGROUND: Greater attention has been paid recently to prenatal mental disorders and their association with exposure to domestic violence (DV) as both have serious reproductive consequences. OBJECTIVES: The aim of this study was to screen for anxiety and/or depression among pregnant women, as well as identify the frequency and association of exposure to DV. PARTICIPANTS AND METHODS: This cross-sectional study was conducted in 2013 and included a systematic random sample of 376 pregnant women attending the antenatal care outpatient clinic at the largest university hospital in Egypt. Participants were interviewed using a structured questionnaire including three components: sociodemographic characteristics of the participants, the Hospital Anxiety and Depression Scale questionnaire (HADS), and the Hurt, Insulted, Threaten, Scream (HITS) inventory for screening for DV. RESULTS: Women who expressed simultaneous anxiety and depressive manifestations accounted for 63%, whereas 11.4% and 10.4% of them expressed only anxiety and only depression, respectively. Exposure to DV was detected in 30.6% of all participants, of whom 25.2% were physically hit by their husbands often to most of the time. Simultaneous anxiety and depression was independently associated with lifetime exposure to DV (odds ratio=3.27, 95% confidence interval: 1.28-8.34, P=0.013), whereas having a university-graduated husband was a protective factor from DV (odds ratio=0.22, 95% confidence interval: 0.64-0.75, P=0.01). CONCLUSION AND RECOMMENDATIONS: Symptoms of anxiety and depression were highly reported among this sample of pregnant Egyptian women and were significantly associated with exposure to intimate partner violence. Screening of pregnant women for mental disorders associated with exposure to DV with provision of supportive mental health services, as well as interventions to reduce exposure to DV, should be considered for integration into antenatal care services. PMID- 26544839 TI - Knowledge, attitudes and practices of adolescents in Upper Egypt on gender-based violence, with a focus on early girls' marriage. AB - BACKGROUND: A large proportion of the female population all over the world, particularly in developing countries, experience some form of gender-based violence (GBV) during their life. Early marriage, a form of GBV, is particularly highly prevalent in rural Upper Egypt. OBJECTIVES: The aim of the current study was to assess the knowledge, attitudes and practices (KAP) of adolescents in Upper Egypt on domestic GBV, with a focus on early girls' marriage. PARTICIPANTS AND METHODS: The study was a cross-sectional descriptive household survey targeting 400 randomly selected adolescent boys and girls aged 11-16 years from five villages of Minya Governorate in Upper Egypt. RESULTS: The proportion of interviewed adolescents who could identify certain practices as forms of GBV was relatively low: the identified practices were mainly deprivation of work (9.0%), deprivation of inheritance (3.3%), arbitrary neglect and desertion (2.8%), and preventing from visiting relatives (0.5%). Abusive sexual behavior was not identified by any of the study participants as a form of domestic GBV. A total of 112 boys (56.0%) reported that they have been perpetrators in domestic GBV events at least once and 118 girls (59.0%) reported that they have been actual victims of domestic GBV. An overall 65.6% of study participants could correctly identify the legal age of marriage as 18 years, yet only 22.0% identified earlier ages of marriage as a form of domestic GBV. The vast majority of girls and boys reported that they would not agree to get married before the age of 18 years (91.0 and 87.0%, respectively). CONCLUSION AND RECOMMENDATIONS: Adolescents in Upper Egypt demonstrated a less than satisfactory knowledge about the forms of GBV. Although early girls' marriage was not universally recognized by adolescents as a form of domestic GBV, they demonstrated satisfactory knowledge about the legal age of marriage, as well as a tendency to abandon the practice. Establishing a community based awareness program for adolescents of both sexes about GBV with a focus on early girls' marriage is highly recommended. PMID- 26544840 TI - Critical thinking and attitude of physicians toward evidence-based medicine in Alexandria, Egypt. AB - BACKGROUND: Evidence-based practice is important for developing countries and is expected to thrive in a questioning culture. Experienced physicians differ in the making of clinical judgements, which are often not based on evidence. Although this topic is of paramount importance to the quality of care provided in the university hospitals in Alexandria, little research has been done about attitudes towards evidence-based medicine (EBM), and the extent of physicians' skills to access and interpret evidence. OBJECTIVE: This study aimed to investigate the relation between the attitude towards EBM and the indicators for questioning mind and critical appraisal skills among physicians in Alexandria, Egypt. PARTICIPANTS AND METHODS: In a cross-sectional study, physicians (N=549) were randomly selected from different clinical departments in three of the university hospitals in Alexandria, Egypt using the stratified proportionate random sampling technique. A self-administrated questionnaire modified from the questionnaire used by McColl and colleagues was used. RESULTS: A high percentage of physicians (83%) had positive attitude towards EBM. Feeling knowledge gap every day was reported by 34.2% of the physicians while 55.6% felt knowledge gap less frequently. The percentage of physicians who understood the meaning of different measures used to assess the importance of results and quality of evidence in meta analysis studies ranged from 10.8 to 24.2%. Higher frequency of feeling knowledge gap in clinical practice and the ability to correctly answer different questions reflecting critical reading skills were all significantly associated with positive attitude towards EBM (P<0.05). A significant association (P<0.05) was also found between the frequency of feeling knowledge gap and the ability to answer questions related to critical reading of literature. CONCLUSION AND RECOMMENDATIONS: This study has identified a significant relation between critical thinking skills and having a positive attitude towards EBM among physicians in the university hospitals in Alexandria. The study supported the hypothesis that strategies that encouraging critical thinking in medical education could improve the attitude of physicians towards EBM. Adopting teaching methods that encourage critical thinking in medical education as well as including the concepts and principals of critical appraisal of scientific research in the syllabus of both undergraduate and postgraduate medical students are recommended. PMID- 26544841 TI - Rotavirus G and P types in children with acute diarrhea in Cairo, Egypt, 2011 2012. AB - BACKGROUND: The WHO estimated the annual rotavirus-related mortality among children below 5 years old in Egypt in 2004 to be 30 deaths per 100 000, or out of an estimated 2616 deaths, 3.9% were because of rotavirus infection. The aim of this article was to study the epidemiology and circulating genotypes of rotaviruses in Cairo from 2011 to 2012. MATERIALS AND METHODS: A total of 197 stool samples were collected from 130 inpatient children at the Cairo University Children Hospital and 67 outpatient children at the Al-Saff Children Clinic. The collected stool samples were then screened for rotavirus using enzyme immunoassay, followed by a screening for G-type and P-type using RT-PCR, and confirmation by sequence analysis. RESULTS: Rotavirus was detected in 39.1% (77/197) of the children, with a higher rate in inpatients (43.9%, 57/130) than in outpatients (29.9%, 20/67). There was an increase of rotavirus infection in the winter season. The majority of rotavirus cases (85.7%) occurred during the first year of life. The predominant genotypes identified during this study were G3P[8] (37.7%) and G1P[8] (19.5%), but uncommon genotypes G1P[6] (3.9%), G9P[6] (1.3%), G8P[14] (1.3%), and G12P[6] (2.6%) were also detected. CONCLUSION AND RECOMMENDATIONS: The change in genotype distribution, compared with previous studies, along with the high burden of rotavirus-associated diarrhea among Egyptian children below 2 years old, emphasizes the importance of continuing strain surveillance and the need of developing and introducing rotavirus vaccine in Egypt. PMID- 26544842 TI - Hypertension in the adult Omani population: predictors for unawareness and uncontrolled hypertension. AB - BACKGROUND: Hypertension is a significant predictor for cardiovascular diseases and is the most important preventable or modifiable cause of morbidity and mortality from these diseases. Undiagnosed cases of hypertension and poor control are important factors in controlling hypertension worldwide, including Oman. AIM OF THE STUDY: The aim of this study was to identify the important risk factors and predictors of the state of unawareness of the presence of hypertension, as well as the risk factors for poor control of blood pressure, among hypertensive patients. MATERIALS AND METHODS: Data from Oman World Health Survey (OWHS), 2008, were used in this study. The OWHS adopted a multistage stratified cluster sampling to select study participants. An interview questionnaire was used to collect data related to risk factors. Other parameters included blood pressure, anthropometric and biochemical measurements. RESULTS: The prevalence of hypertension in Oman was estimated to be 41.5%. Of those who were hypertensive, three-quarters of them (75.7%) were unaware of being hypertensive and 65.5% of them had inadequately controlled hypertension. Male sex, higher wealth, and paying fewer visits to health facilities were found associated with high proportions of unawareness and high proportion of uncontrolled hypertension. CONCLUSION AND RECOMMENDATIONS: The study highlights high levels of unawareness of being hypertensive and high proportion of uncontrolled hypertension in Oman that need to be considered when developing health policies and strategies. Intersectorial collaborative and innovative strategies that focus on improving awareness, detection, and control of hypertension should be considered, especially with attention to young adults and men. PMID- 26544843 TI - Genotype-phenotype relationship among Egyptian children with Rett syndrome. AB - BACKGROUND: Rett syndrome (RTT) is an X-linked dominant neurodegenerative disorder with various MECP2 mutations. RTT is one of the most common causes of severe intellectual and complex disability in girls. Therefore, the aims of the study were as follows: to highlight the clinical manifestations of RTT; to present the genotype-phenotype relationship; and to assess the possible relation between severity score, clinical manifestations, and MECP2 gene mutations. PATIENTS AND METHODS: The present cross-sectional study included 15 girls with typical RTT, diagnosed according to the international criteria of RTT. All included patients were followed up at the pediatric neurology clinic, Cairo University Specialized Pediatric Hospital. They were subjected to screening of the entire coding region of the MECP2 gene (MECP2A and MECP2B) using denaturing high-performance liquid chromatography. The clinical severity was assessed among RTT cases using the International Scoring System. RESULTS: Stereotypic hand movements were present in all cases, acquired microcephaly was present in 73.3% of cases, autistic features in 66.7% of cases, recurrent seizures in 53.3% of cases, delayed language development in 46.6% of cases, deterioration of speech in 53.3% of cases, and growth retardation and peripheral vasomotor changes in 46.6% of cases. Positive mutations were detected in 10 cases (66.66%): heterozygous for p.R270X mutation (three cases), heterozygous for p.R255X mutation (three cases), and heterozygous for p.R168X nonsense mutation (four cases). Microcephaly, seizures, growth retardation, and autistic features were more frequent in patients with a mutated gene; it was also observed that walking ability was more frequent in patients without a mutation.; thus, genotype-phenotype relationship was confirmed. The relationship between severity score and MECP2 mutation was detected in three cases with severe RTT, but there was no relationship between the severity score and specific MECP2 mutation. There was a relationship between the severity score and the clinical manifestations of RTT. CONCLUSION: Mutations of MECP2 analysis were detected in 66.7% of RTT cases. There were relationships between the severity score, clinical manifestations, and MECP2 gene mutations. However, there was no relationship between the severity score and specific MECP2 gene mutation. PMID- 26544844 TI - Improved health markers among fasting diabetes patients during Ramadan--an educational role for pharmacists. PMID- 26544845 TI - Insect Biometrics: Optoacoustic Signal Processing and Its Applications to Remote Monitoring of McPhail Type Traps. AB - Monitoring traps are important components of integrated pest management applied against important fruit fly pests, including Bactrocera oleae (Gmelin) and Ceratitis capitata (Widemann), Diptera of the Tephritidae family, which effect a crop-loss/per year calculated in billions of euros worldwide. Pests can be controlled with ground pesticide sprays, the efficiency of which depends on knowing the time, location and extent of infestations as early as possible. Trap inspection is currently carried out manually, using the McPhail trap, and the mass spraying is decided based on a decision protocol. We introduce the term 'insect biometrics' in the context of entomology as a measure of a characteristic of the insect (in our case, the spectrum of its wingbeat) that allows us to identify its species and make devices to help face old enemies with modern means. We modify a McPhail type trap into becoming electronic by installing an array of photoreceptors coupled to an infrared emitter, guarding the entrance of the trap. The beating wings of insects flying in the trap intercept the light and the light fluctuation is turned to a recording. Custom-made electronics are developed that are placed as an external add-on kit, without altering the internal space of the trap. Counts from the trap are transmitted using a mobile communication network. This trap introduces a new automated remote-monitoring method different to audio and vision-based systems. We evaluate our trap in large number of insects in the laboratory by enclosing the electronic trap in insectary cages. Our experiments assess the potential of delivering reliable data that can be used to initialize reliably the spraying process at large scales but to also monitor the impact of the spraying process as it eliminates the time-lag between acquiring and delivering insect counts to a central agency. PMID- 26544846 TI - Anthocyanin Extracted from Black Soybean Seed Coats Prevents Autoimmune Arthritis by Suppressing the Development of Th17 Cells and Synthesis of Proinflammatory Cytokines by Such Cells, via Inhibition of NF-kappaB. AB - INTRODUCTION: Oxidative stress plays a role in the pathogenesis of rheumatoid arthritis (RA). Anthocyanin is a plant antioxidant. We investigated the therapeutic effects of anthocyanin extracted from black soybean seed coats (AEBS) in a murine model of collagen-induced arthritis (CIA) and human peripheral blood mononuclear cells (PBMCs) and explored possible mechanisms by which AEBS might exert anti-arthritic effects. MATERIAL AND METHODS: CIA was induced in DBA/1J mice. Cytokine levels were measured via enzyme-linked immunosorbent assays. Joints were assessed in terms of arthritis incidence, clinical arthritis scores, and histological features. The extent of oxidative stress in affected joints was determined by measuring the levels of nitrotyrosine and inducible nitric oxide synthase. NF-kappaB activity was assayed by measuring the ratio of phosphorylated IkappaB to total IkappaB via Western blotting. Th17 cells were stained with antibodies against CD4, IL-17, and STAT3. Osteoclast formation was assessed via TRAP staining and measurement of osteoclast-specific mRNA levels. RESULTS: In the CIA model, AEBS decreased the incidence of arthritis, histological inflammation, cartilage scores, and oxidative stress. AEBS reduced the levels of proinflammatory cytokines in affected joints of CIA mice and suppressed NF-kappaB signaling. AEBS decreased Th17 cell numbers in spleen of CIA mice. Additionally, AEBS repressed differentiation of Th17 cells and expression of Th17-associated genes in vitro, in both splenocytes of naive DBA/1J mice and human PBMCs. In vitro, the numbers of both human and mouse tartrate-resistant acid phosphatase+ (TRAP) multinucleated cells fell, in a dose-dependent manner, upon addition of AEBS. CONCLUSIONS: The anti-arthritic effects of AEBS were associated with decreases in Th17 cell numbers, and the levels of proinflammatory cytokines synthesized by such cells, mediated via suppression of NF-kappaB signaling. Additionally, AEBS suppressed osteoclastogenesis and reduced oxidative stress levels. PMID- 26544847 TI - Regulated CRISPR Modules Exploit a Dual Defense Strategy of Restriction and Abortive Infection in a Model of Prokaryote-Phage Coevolution. AB - CRISPRs offer adaptive immunity in prokaryotes by acquiring genomic fragments from infecting phage and subsequently exploiting them for phage restriction via an RNAi-like mechanism. Here, we develop and analyze a dynamical model of CRISPR mediated prokaryote-phage coevolution that incorporates classical CRISPR kinetics along with the recently discovered infection-induced activation and autoimmunity side effects. Our analyses reveal two striking characteristics of the CRISPR defense strategy: that both restriction and abortive infections operate during coevolution with phages, driving phages to much lower densities than possible with restriction alone, and that CRISPR maintenance is determined by a key dimensionless combination of parameters, which upper bounds the activation level of CRISPRs in uninfected populations. We contrast these qualitative observations with experimental data on CRISPR kinetics, which offer insight into the spacer deletion mechanism and the observed low CRISPR prevalence in clinical isolates. More generally, we exploit numerical simulations to delineate four regimes of CRISPR dynamics in terms of its host, kinetic, and regulatory parameters. PMID- 26544848 TI - Physical Fitness Percentiles of German Children Aged 9-12 Years: Findings from a Longitudinal Study. AB - BACKGROUND: Generating percentile values is helpful for the identification of children with specific fitness characteristics (i.e., low or high fitness level) to set appropriate fitness goals (i.e., fitness/health promotion and/or long-term youth athlete development). Thus, the aim of this longitudinal study was to assess physical fitness development in healthy children aged 9-12 years and to compute sex- and age-specific percentile values. METHODS: Two-hundred and forty children (88 girls, 152 boys) participated in this study and were tested for their physical fitness. Physical fitness was assessed using the 50-m sprint test (i.e., speed), the 1-kg ball push test, the triple hop test (i.e., upper- and lower- extremity muscular power), the stand-and-reach test (i.e., flexibility), the star run test (i.e., agility), and the 9-min run test (i.e., endurance). Age- and sex-specific percentile values (i.e., P10 to P90) were generated using the Lambda, Mu, and Sigma method. Adjusted (for change in body weight, height, and baseline performance) age- and sex-differences as well as the interactions thereof were expressed by calculating effect sizes (Cohen's d). RESULTS: Significant main effects of Age were detected for all physical fitness tests (d = 0.40-1.34), whereas significant main effects of Sex were found for upper extremity muscular power (d = 0.55), flexibility (d = 0.81), agility (d = 0.44), and endurance (d = 0.32) only. Further, significant Sex by Age interactions were observed for upper-extremity muscular power (d = 0.36), flexibility (d = 0.61), and agility (d = 0.27) in favor of girls. Both, linear and curvilinear shaped curves were found for percentile values across the fitness tests. Accelerated (curvilinear) improvements were observed for upper-extremity muscular power (boys: 10-11 yrs; girls: 9-11 yrs), agility (boys: 9-10 yrs; girls: 9-11 yrs), and endurance (boys: 9-10 yrs; girls: 9-10 yrs). Tabulated percentiles for the 9 min run test indicated that running distances between 1,407-1,507 m, 1,479-1,597 m, 1,423-1,654 m, and 1,433-1,666 m in 9- to 12-year-old boys and 1,262-1,362 m, 1,329-1,434 m, 1,392-1,501 m, and 1,415-1,526 m in 9- to 12-year-old girls correspond to a "medium" fitness level (i.e., P40 to P60) in this population. CONCLUSIONS: The observed differences in physical fitness development between boys and girls illustrate that age- and sex-specific maturational processes might have an impact on the fitness status of healthy children. Our statistical analyses revealed linear (e.g., lower-extremity muscular power) and curvilinear (e.g., agility) models of fitness improvement with age which is indicative of timed and capacity-specific fitness development pattern during childhood. Lastly, the provided age- and sex-specific percentile values can be used by coaches for talent identification and by teachers for rating/grading of children's motor performance. PMID- 26544850 TI - High-throughput platforms for metabolomics. AB - Mass spectrometry has become a choice method for broad-spectrum metabolite analysis in both fundamental and applied research. This can range from comprehensive analysis achieved through time-consuming chromatography to the rapid analysis of a few target metabolites without chromatography. In this review article, we highlight current high-throughput MS-based platforms and their potential application in metabolomics. Although current MS platforms can reach throughputs up to 0.5 seconds per sample, the metabolite coverage of these platforms are low compared to low-throughput, separation-based MS methods. High throughput comes at a cost, as it's a trade-off between sample throughput and metabolite coverage. As we will discuss, promising emerging technologies, including microfluidics and miniaturization of separation techniques, have the potential to achieve both rapid and more comprehensive metabolite analysis. PMID- 26544849 TI - The Pectin Methylesterase Gene Complement of Phytophthora sojae: Structural and Functional Analyses, and the Evolutionary Relationships with Its Oomycete Homologs. AB - Phytophthora sojae is an oomycete pathogen that causes the disease known as root and stem rot in soybean plants, frequently leading to massive economic damage. Additionally, P. sojae is increasingly being utilized as a model for phytopathogenic oomycete research. Despite the economic and scientific importance of P. sojae, the mechanism by which it penetrates the host roots is not yet fully understood. It has been found that oomycetes are not capable of penetrating the cell wall solely through mechanical force, suggesting that alternative factors facilitate breakdown of the host cell wall. Pectin methylesterases have been suggested to be important for Phytophthora pathogenicity, but no data exist on their role in the P. sojae infection process. We have scanned the newly revised version of the annotated P. sojae genome for the presence of putative pectin methylesterases genes and conducted a sequence analysis of all gene models found. We also searched for potential regulatory motifs in the promoter region of the proposed P. sojae models, and investigated the gene expression levels throughout the early course of infection on soybean plants. We found that P. sojae contains a large repertoire of pectin methylesterase-coding genes and that most of these genes display similar motifs in the promoter region, indicating the possibility of a shared regulatory mechanism. Phylogenetic analyses confirmed the evolutionary relatedness of the pectin methylesterase-coding genes within and across Phytophthora spp. In addition, the gene duplication events that led to the emergence of this gene family appear to have occurred prior to many speciation events in the genus Phytophthora. Our results also indicate that the highest levels of expression occurred in the first 24 hours post inoculation, with expression falling after this time. Our study provides evidence that pectin methylesterases may be important for the early action of the P. sojae infection process. PMID- 26544851 TI - Two Polyhydroxyalkanoate Synthases from Distinct Classes from the Aromatic Degrader Cupriavidus pinatubonensis JMP134 Exhibit the Same Substrate Preference. AB - Cupriavidus pinatubonensis JMP134 utilizes a variety of aromatic substrates as sole carbon sources, including meta-nitrophenol (MNP). Two polyhydroxyalkanoate (PHA) synthase genes, phaC1 and phaC2, were annotated and categorized as class I and class II PHA synthase genes, respectively. In this study, both His-tagged purified PhaC1 and PhaC2 were shown to exhibit typical class I PHA synthase substrate specificity to make short-chain-length (SCL) PHA from 3-hydroxybutyryl CoA and failed to make medium-chain-length (MCL) PHA from 3-hydroxyoctanoyl-CoA. The phaC1 or phaC2 deletion strain could also produce SCL PHA when grown in fructose or octanoate, but the double mutant of phaC1 and phaC2 lost this ability. The PhaC2 also exhibited substrate preference towards SCL substrates when expressed in Pseudomonas aeruginosa PAO1 phaC mutant strain. On the other hand, the transcriptional level of phaC1 was 70-fold higher than that of phaC2 in MNP-grown cells, but 240-fold lower in octanoate-grown cells. Further study demonstrated that only phaC1 was involved in PHA synthesis in MNP-grown cells. These findings suggested that phaC1 and phaC2 genes were differentially regulated under different growth conditions in this strain. Within the phaC2-containing gene cluster, a single copy of PHA synthase gene was present clustering with genes encoding enzymes in the biosynthesis of PHA precursors. This is markedly different from the genetic organization of all other previously reported class II PHA synthase gene clusters and this cluster likely comes from a distinct evolutionary path. PMID- 26544854 TI - Radial Extracorporeal Shock Wave Therapy Is Not More Effective Than Placebo in the Management of Lateral Epicondylitis: A Double-Blind, Randomized, Placebo Controlled Trial. AB - OBJECTIVES: The aim of this study was to investigate the effects of radial extracorporeal shock wave therapy (rESWT) on pain, function, and grip strength in the treatment of patients with lateral epicondylitis unresponsive to previous treatments. DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in outpatient clinics in a medical faculty hospital. Fifty-six patients with lateral epicondylitis were randomized to rESWT (n = 28) or sham rESWT (n = 28) groups. Both the patients and the outcome assessing investigator were blinded to group assignment. The rESWT was administered to the painful epicondyle at the elbow with a total of 2000 pulses of 10 Hz frequency at a 1.8 bar of air pressure at each session at three once weekly sessions. Sham rESWT was applied without the contact of the applicator at the same area. Study patients were assessed at baseline and at 1 and 3 mos after treatment using a visual analog scale for pain and Roles and Maudsley scale and Patient-Rated Tennis Elbow Evaluation for pain and function. Grip strength of the affected extremity was also measured using a hand dynamometer. RESULTS: Both rESWT and sham rESWT groups showed a significant improvement in all outcome measures at posttreatment follow-up points. Favorable absolute and percentage changes in assessments at 1- and 3-mo posttreatment did not show any significant difference between groups. CONCLUSIONS: The rESWT does not seem to be more effective either in reducing pain or improving function or grip strength in patients with lateral epicondylitis at least at 3 mos after treatment when compared with sham rESWT. PMID- 26544852 TI - Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach. AB - INTRODUCTION: Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression. METHOD: We performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20) and healthy control women (n = 20). RESULTS: Unbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p<0.05, fold change >3). Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS) samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131), early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014), filaggrin and MMRN2) and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10). Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin) identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively. CONCLUSIONS: Our results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers) identified, have potential for clinical use in the detection of BC. Validation with a larger independent cohort of patients is required in the following study. PMID- 26544853 TI - A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART. AB - TRIAL DESIGN: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. METHODS: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. RESULTS: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses. CONCLUSION: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571466. PMID- 26544855 TI - Injury of the Thalamocingulate Tract in the Papez Circuit in Patients with Mild Traumatic Brain Injury. AB - The thalamocingulate tract between the anterior thalamic nuclei and the cingulate gyrus is a part of the Papez circuit. Using diffusion tensor tractography, injury of the thalamocingulate tract was investigated in patients with mild traumatic brain injury. Two patients (patient 1: a 58-yr-old woman and patient 2: a 49-yr old man) with head trauma resulting from a car accident were enrolled. They were classified as mild traumatic brain injury and no specific lesion was observed on brain magnetic resonance imaging. These patients complained of memory impairment after head trauma. The entire Papez circuits, including thalamocingulate tract, fornix, mammillothalamic tract, and cingulum, were reconstructed in both hemispheres except for the left thalamocingulate tract: patient 1, it was thinner and discontinued compared with the right thalamocingulate tract; and patient 2, it was not reconstructed. The injury of the left thalamocingulate tract appeared to be related to the memory impairment in these patients. PMID- 26544856 TI - Using Functional Status in the Acute Hospital to Predict Discharge Destination for Stroke Patients. AB - OBJECTIVE: The aim of this study was to determine whether functional status, as measured by the AcuteFIM instrument, can be used to predict discharge destination of stroke patients from the acute hospital setting. DESIGN: A retrospective cohort study was carried out in an urban academic medical center. Data were collected on 481 new-onset stroke patients 18 yrs or older in an acute hospital between January 1 and September 30, 2013. Functional Independence Measure (FIM) instrument data were linked to a subset of 54 patients who received additional services at an inpatient rehabilitation facility. A receiver operator characteristic curve was constructed to validate the predictive ability of the AcuteFIM instrument and to determine the optimal cutoff score associated with discharge to a community setting. RESULTS: All AcuteFIM items in stroke patients at admission demonstrated strong interitem correlation coefficients (all above 0.6) and high internal consistency (Cronbach alpha = 0.94). The AcuteFIM total score was positively associated with discharge to the community from the acute hospital (odds ratio, 1.06; 95% confidence interval, 1.05-1.07). Receiver operator characteristic curve analysis generated a c statistic of 0.89 (95% confidence interval, 0.87-0.92), indicating that the AcuteFIM instrument is predictive of patient discharge to the community setting. CONCLUSION: This study suggests that the AcuteFIM instrument is a reliable tool that can be used to predict discharge destination from the acute hospital among stroke patients. PMID- 26544857 TI - Effect of Aerobic Exercise Interventions on Mobility among Stroke Patients: A Systematic Review. AB - OBJECTIVE: The purpose of this systematic review was to examine studies that examined the effectiveness of aerobic exercise interventions on mobility in long term stroke survivors. DESIGN: The authors searched electronic databases for randomized control trials between January 1995 and December 2014 investigating aerobic exercise interventions and mobility in stroke survivors after the subacute phase (>6 mos). Mobility was measured using objective functional fitness tests: 6-minute walk, 10-meter walk, and up-n-go. RESULTS: Nine randomized control trials that compared aerobic exercise with a control group among stroke survivors (mean age, 56.95-68 yrs) were identified. Aerobic interventions lasted between 2 and 6 mos and primarily involved walking. Using the Comprehensive Meta analysis software, it was found that two of the three mobility outcomes showed small to moderate effect sizes favoring the aerobic exercise group: 6-minute walk (g = 0.366, P < 0.001) and 10-meter walk (g = 0.411, P = 0.002), while the up-n go test was not significant (g = -0.150, P = 0.330). CONCLUSION: These findings demonstrate that stroke survivors may continue to benefit from aerobic exercise after the subacute phase. Future research needs to examine the precise dose and recommendation for aerobic exercise, test other exercise modalities, and use larger samples to thoroughly determine long-term exercise effects on mobility in this population. PMID- 26544858 TI - Noninvasive PCO2 Monitoring During Sleep for Patients with Neuromuscular Disease. PMID- 26544859 TI - Effects of Virtual Walking Treatment on Spinal Cord Injury-Related Neuropathic Pain: Pilot Results and Trends Related to Location of Pain and at-level Neuronal Hypersensitivity. AB - Previous studies have shown that virtual walking to treat spinal cord injury related neuropathic pain (SCI-NP) can be beneficial, although the type of SCI-NP that may benefit the most is unclear. This study's aims were to (1) determine the effect of location of SCI-NP on pain outcomes after virtual walking treatment and (2) examine the potential relationship between neuronal hyperexcitability, as measured by quantitative sensory testing, and pain reduction after virtual walking treatment. Participants were recruited from a larger ongoing trial examining the benefits of virtual walking in SCI-NP. Neuropathic pain was classified according to location of pain (at- or below-level). In addition, quantitative sensory testing was performed on a subset of individuals at a nonpainful area corresponding to the level of their injury before virtual walking treatment and was used to characterize treatment response. These pilot results suggest that when considered as a group, SCI-NP was responsive to treatment irrespective of the location of pain (F1, 44 = 4.82, P = 0.03), with a trend for the greatest reduction occurring in at-level SCI-NP (F1, 44 = 3.18, P = 0.08). These pilot results also potentially implicate cold, innocuous cool, and pressure hypersensitivity at the level of injury in attenuating the benefits of virtual walking to below-level pain, suggesting certain SCI-NP sensory profiles may be less responsive to virtual walking. PMID- 26544860 TI - Deciphering Transcriptional Dynamics In Vivo by Counting Nascent RNA Molecules. AB - Deciphering how the regulatory DNA sequence of a gene dictates its expression in response to intra and extracellular cues is one of the leading challenges in modern genomics. The development of novel single-cell sequencing and imaging techniques, as well as a better exploitation of currently available single molecule imaging techniques, provides an avenue to interrogate the process of transcription and its dynamics in cells by quantifying the number of RNA polymerases engaged in the transcription of a gene (or equivalently the number of nascent RNAs) at a given moment in time. In this paper, we propose that measurements of the cell-to-cell variability in the number of nascent RNAs provide a mostly unexplored method for deciphering mechanisms of transcription initiation in cells. We propose a simple kinetic model of transcription initiation and elongation from which we calculate nascent RNA copy-number fluctuations. To demonstrate the usefulness of this approach, we test our theory against published nascent RNA data for twelve constitutively expressed yeast genes. Rather than transcription being initiated through a single rate limiting step, as it had been previously proposed, our single-cell analysis reveals the presence of at least two rate limiting steps. Surprisingly, half of the genes analyzed have nearly identical rates of transcription initiation, suggesting a common mechanism. Our analytical framework can be used to extract quantitative information about dynamics of transcription from single-cell sequencing data, as well as from single-molecule imaging and electron micrographs of fixed cells, and provides the mathematical means to exploit the quantitative power of these technologies. PMID- 26544861 TI - Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats. AB - Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia. PMID- 26544862 TI - Fetal Sex Modulates Developmental Response to Maternal Malnutrition. AB - The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys) at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol) favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype. PMID- 26544863 TI - Experimental and Mathematical-Modeling Characterization of Trypanosoma cruzi Epimastigote Motility. AB - The present work is aimed at characterizing the motility of parasite T. cruzi in its epimastigote form. To that end, we recorded the trajectories of two strains of this parasite (a wild-type strain and a stable transfected strain, which contains an ectopic copy of LYT1 gene and whose motility is known to be affected). We further extracted parasite trajectories from the recorded videos, and statistically analysed the following trajectory-step features: step length, angular change of direction, longitudinal and transverse displacements with respect to the previous step, and mean square displacement. Based on the resulting observations, we developed a mathematical model to simulate parasite trajectories. The fact that the model predictions closely match most of the experimentally observed parasite-trajectory characteristics, allows us to conclude that the model is an accurate description of T. cruzi motility. PMID- 26544864 TI - Alignment of the Fibrin Network Within an Autologous Plasma Clot. AB - Autologous plasma clots with longitudinally aligned fibrin fibers could serve as a scaffold for longitudinal axonal regrowth in cases of traumatic peripheral nerve injuries. Three different techniques for assembling longitudinally oriented fibrin fibers during the fibrin polymerization process were investigated as follows: fiber alignment was induced by the application of either a magnetic field or-as a novel approach-electric field or by the induction of orientated flow. Fiber alignment was characterized by scanning electron microscopy analysis followed by image processing using fast Fourier transformation (FFT). Besides FFT output images, area xmin to xmax, as well as full width at half maximum (FWHM) of the FFT graph plot peaks, was calculated to determine the relative degree of fiber alignment. In addition, fluorescently labeled human fibrinogen and mesenchymal stem cells (MSCs) were used to visualize fibrin and cell orientation in aligned and nonaligned plasma clots. Varying degrees of fiber alignment were achieved by the three different methods, with the electric field application producing the highest degree of fiber alignment. The embedded MSCs showed a longitudinal orientation in the electric field-aligned plasma clots. The key feature of this study is the ability to produce autologous plasma clots with aligned fibrin fibers using physical techniques. This orientated internal structure of an autologous biomaterial is promising for distinct therapeutic applications, such as a guiding structure for cell migration and growth dynamics. PMID- 26544865 TI - Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China. AB - OBJECTIVE: The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. DESIGN: A retrospective cohort study. PARTICIPANTS: Seventy-nine patients with renal biopsy proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. RESULTS: In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn't reach statistical meanings (P = 0.104). CONCLUSION: Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID- 26544866 TI - Up-Regulation of S100A11 in Lung Adenocarcinoma - Its Potential Relationship with Cancer Progression. AB - We previously reported that patients with lung adenocarcinomas with KRAS gene mutations and strong proliferating activity had poorer outcomes, even in the early stage of the disease. The aim of the present study was to elucidate the potential molecular basis of these highly malignant lung tumors by focusing on S100 proteins (S100A2, S100A7, and S100A11), which are downstream targets of oncogenic KRAS and promoters of tumor progression. The immunohistochemical expression of S100 proteins was examined in 179 primary lung adenocarcinomas, and the potential relationships between their levels and clinicopathologic factors were analyzed. Among the three subtypes, S100A11 levels were significantly higher in adenocarcinomas with KRAS mutations and strong proliferating activity. They were also higher in adenocarcinomas with poorly differentiated tumors. Furthermore, higher levels of S100A11 were associated with shorter disease-free survival. These results suggest that the up-regulation of S100A11 plays a role in tumor progression, particularly in KRAS-mutated lung adenocarcinomas. PMID- 26544869 TI - One-pot synthesis of carbon dots-embedded molecularly imprinted polymer for specific recognition of sterigmatocystin in grains. AB - A novel sensitive fluorescent sensor for determination of sterigmatocystin (ST), which was based on carbon dots-embedded molecularly imprinted polymer (CDs@MIP), was prepared by an efficient one-pot reaction. First, highly blue luminescent CDs were synthesized via a one-step reaction. Then, through a non-hydrolytic sol-gel process, MIP was formed on the CDs surface in the presence of 1,8 dihydroxyanthraquinone as an alternative template molecule to obtain CDs@MIP. The CDs acted as antennas for signal amplification and optical readout, and the MIP coated on the CDs surface provided specific binding sites for ST. The performance of CDs@MIP was compared with that of CDs embedded in non-imprinted polymer (CDs@NIP). CDs@MIP exhibited high selectivity and sensitivity toward ST. Under optimized conditions, the relative fluorescence intensity of CDs@MIP decreased linearly with the concentration of ST from 0.05 to 2.0 mgL(-1) with a detection limit of 0.019 mgL(-1) (S/N=3) and the precision for five replicate detections of 0.10 mgL(-1) ST was 2.31%. The sensor was also used to determine the content of ST in grains with satisfactory results. PMID- 26544867 TI - Drosophila Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior. AB - Individuals with Cornelia de Lange Syndrome (CdLS) display diverse developmental deficits, including slow growth, multiple limb and organ abnormalities, and intellectual disabilities. Severely-affected individuals most often have dominant loss-of-function mutations in the Nipped-B-Like (NIPBL) gene, and milder cases often have missense or in-frame deletion mutations in genes encoding subunits of the cohesin complex. Cohesin mediates sister chromatid cohesion to facilitate accurate chromosome segregation, and NIPBL is required for cohesin to bind to chromosomes. Individuals with CdLS, however, do not display overt cohesion or segregation defects. Rather, studies in human cells and model organisms indicate that modest decreases in NIPBL and cohesin activity alter the transcription of many genes that regulate growth and development. Sister chromatid cohesion factors, including the Nipped-B ortholog of NIPBL, are also critical for gene expression and development in Drosophila melanogaster. Here we describe how a modest reduction in Nipped-B activity alters growth and neurological function in Drosophila. These studies reveal that Nipped-B heterozygous mutant Drosophila show reduced growth, learning, and memory, and altered circadian rhythms. Importantly, the growth deficits are not caused by changes in systemic growth controls, but reductions in cell number and size attributable in part to reduced expression of myc (diminutive) and other growth control genes. The learning, memory and circadian deficits are accompanied by morphological abnormalities in brain structure. These studies confirm that Drosophila Nipped-B mutants provide a useful model for understanding CdLS, and provide new insights into the origins of birth defects. PMID- 26544870 TI - Enzymatic-induced upconversion photoinduced electron transfer for sensing tyrosine in human serum. AB - This paper reports a novel nanosensor for tyrosine based on photoinduced electron transfer (PET) between NaYF4:Yb, Tm upconversion nanoparticles (UCNPs) and melanin-like polymers. Melanin-like films were obtained from catalytic oxidation of tyrosine by tyrosinase, and deposited on the surface of UCNPs, and then quenched the fluorescence of UCNPs. Under the optimized conditions, the fluorescence quenching of UCNPs showed a good linear response to tyrosine concentration in the range of 0.8-100 MUMU with a detection limit of 1.1 MUMU. Meanwhile, it showed good sensitivity, stability and has been successfully applied to the detection of tyrosine in human serum. PMID- 26544868 TI - Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis. AB - MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was confirmed in human prostate tumor samples as compared to adjacent benign glandular epithelium collected through laser capture microdissection from radical prostatectomies. In fact, alterations in hsa-miR 125b expression appeared to be an early event in tumorigenesis. Reverse phase microarray proteomic analysis revealed ErbB2/3 and downstream members of the PI3K/AKT and MAPK/ERK pathways as well as PTEN to be protein targets differentially expressed in the M12 tumor cell compared to its parental p69 cell. Relevant luciferase+3'-UTR expression studies confirmed a direct interaction between hsa-miR-125b and ErbB2 and between hsa-miR-22 and PTEN. Restoration of hsa-miR-125b or inhibition of hsa-miR-22 expression via an antagomiR resulted in an alteration of M12 tumor cell behavior in vitro. Thus, the dual action of hsa miR-125b as a tumor suppressor and hsa-miR-22 as an oncomiR contributed to prostate tumorigenesis by modulations in PI3K/AKT and MAPK/ERK signaling pathways, key pathways known to influence prostate cancer progression. PMID- 26544871 TI - Label-free amino acid detection based on nanocomposites of graphene oxide hybridized with gold nanoparticles. AB - Nanocomposites of graphene oxide and gold nanoparticles (GO/GNPs) were synthesized for label-free detections of amino acids. Interactions between the composites and amino acids were investigated by both naked-eye observation and optical absorption spectroscopy. The GO/GNPs composites displayed apparent color changes and absorption spectra changes in presences of amino acids including glutamate, aspartate, and cysteine. The interaction mechanisms of the composites and amino acids were discussed and explored with sulfhydryl groups and non-alpha carboxylic groups on the amino acids. Sensing properties of the composites were tested, while pure gold particles were used as the control. The results suggested that the GO/GNPs composites had better linearity and stability in dose-dependent responses to the amino acids than those of the particles, especially in detections for acidic amino acids. Therefore, the nanocomposites platform can provide a convenient and efficient approach for label-free optical detections of important molecules such as amino acids. PMID- 26544872 TI - Optimization of strand displacement amplification-sensitized G-quadruplex DNAzyme based sensing system and its application in activity detection of uracil-DNA glycosylase. AB - As an isothermal nucleic acid amplification technique, strand displacement amplification (SDA) reaction has been introduced in G-quadruplex DNAzyme-based sensing system to improve the sensing performance. To further provide useful information for the design of SDA-amplified G-quadruplex DNAzyme-based sensors, the effects of nicking site number in SDA template DNA were investigated. With the increase of the nicking site number from 1 to 2, enrichment of G-quadruplex DNAzyme by SDA is changed from a linear amplification to an exponential amplification, thus greatly increasing the amplification efficiency and subsequently improving the sensing performance of corresponding sensing system. The nicking site number cannot be further increased because more nicking sites might result in high background signals. However, we demonstrated that G quadruplex DNAzyme enrichment efficiency could be further improved by introducing a cross-triggered SDA strategy, in which two templates each has two nicking sites are used. To validate the proposed cross-triggered SDA strategy, we used it to develop a sensing platform for the detection of uracil-DNA glycosylase (UDG) activity. The sensor enables sensitive detection of UDG activity in the range of 1 * 10(-4)-1 U/mL with a detection limit of 1 * 10(-4)U/mL. PMID- 26544873 TI - An ultrasensitive human cardiac troponin T graphene screen-printed electrode based on electropolymerized-molecularly imprinted conducting polymer. AB - A nano-molecularly imprinted polymer (N-MIP) assembled on a screen-printed electrode for the cardiac troponin T (cTnT) was developed. The biomimetic surface was obtained by a co-polymer matrix assembled on the reduced graphene oxide (RGO) electrode surface. The cTnT active sites were engineered using pyrrole and carboxylated pyrrole that was one-step electropolymerized jointly with cTnT by cyclic voltammetry. The stepwise preparation of the biomimetic surface was characterized by cyclic and differential pulse voltammetries using the ferrocyanide/ferricyanide as redox probe. Structural and morphological characterization was also performed. The optimal relation of pyrrole and pyrrole 3-acid carboxylic to perform the cTnT biomimetic nanosurface was obtained at 1:5 ratio. The analytical performance of cTnT N-MIP performed by differential pulse voltammetry showed a linear range from 0.01 to 0.1 ngmL(-1) (r=0.995, p"0.01), with a very low limit of detection (0.006 ngmL(-1)). The synergic effect of conductive polymer and graphene forming 3D structures of reactive sites resulted in a N-MIP with excellent affinity to cTnT binding (KD=7.3 10(-13) molL(-1)). The N-MIP proposed is based on a simple method of antibody obtaining with a large potential for point-of-care testing applications. PMID- 26544874 TI - Cytochrome P450 Oxidoreductase Influences CYP2B6 Activity in Cyclophosphamide Bioactivation. AB - INTRODUCTION: Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies. MATERIALS AND METHODS: Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined. RESULTS: A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 MUL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression. CONCLUSIONS: This investigation shows for the first time that POR besides CYP2B6 can influence cyclophosphamide metabolism. Our results indicate that not only CYPs are important, but also POR expression and/or activity may influence cyclophosphamide bioactivation, affecting therapeutic efficacy and treatment related toxicity and hence on clinical outcome. Thus, both POR and CYP genotype and expression levels may have to be taken into account when personalizing treatment schedules to achieve optimal therapeutic drug plasma concentrations of cyclophosphamide. PMID- 26544876 TI - Modeling Coevolution between Language and Memory Capacity during Language Origin. AB - Memory is essential to many cognitive tasks including language. Apart from empirical studies of memory effects on language acquisition and use, there lack sufficient evolutionary explorations on whether a high level of memory capacity is prerequisite for language and whether language origin could influence memory capacity. In line with evolutionary theories that natural selection refined language-related cognitive abilities, we advocated a coevolution scenario between language and memory capacity, which incorporated the genetic transmission of individual memory capacity, cultural transmission of idiolects, and natural and cultural selections on individual reproduction and language teaching. To illustrate the coevolution dynamics, we adopted a multi-agent computational model simulating the emergence of lexical items and simple syntax through iterated communications. Simulations showed that: along with the origin of a communal language, an initially-low memory capacity for acquired linguistic knowledge was boosted; and such coherent increase in linguistic understandability and memory capacities reflected a language-memory coevolution; and such coevolution stopped till memory capacities became sufficient for language communications. Statistical analyses revealed that the coevolution was realized mainly by natural selection based on individual communicative success in cultural transmissions. This work elaborated the biology-culture parallelism of language evolution, demonstrated the driving force of culturally-constituted factors for natural selection of individual cognitive abilities, and suggested that the degree difference in language-related cognitive abilities between humans and nonhuman animals could result from a coevolution with language. PMID- 26544875 TI - Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis. AB - Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a "druggable" essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivalis was first expressed and purified in Escherichia coli then characterized for enzymatic inhibitor screening studies. Several inhibitors with similar structural scaffolds containing a sulfonamide core and aromatic substituents showed dose dependent inhibition. These compounds were further assayed showing reasonable whole-cell activity and the inhibition mechanism was determined. We conclude that the establishment of this target and screening strategy provides a model for the future development of new antimicrobials. PMID- 26544877 TI - Nutritional Therapy for Critically Ill Patients. AB - Nutrition therapy provided early in the critical care setting has been shown to improve outcome. Appropriate and early nutrition interventions can attenuate the hyperdynamic systemic response and depressed immune reaction to injury, serious illness and major surgery. Controversies limit the uniform application and potential benefits of nutrition, including failure to accurately predict who will 'need' nutritional intervention, lack of consensus on what the optimal enteral formulation is, overreliance on parenteral nutrition, failure to maximize the use of early enteral nutrition (EN), and how much and how best to feed the morbidly obese population. Despite challenges and inconsistencies in today's critical care setting, specialized nutrition has evolved from metabolic 'support' during critical illness to a primary therapeutic intervention designed, individualized and focused to achieve metabolic optimization and mitigation of stress-induced immune and hyperdynamic systemic responses. Nutrition should be considered early and commenced after initial resuscitation has taken place. This is most effectively accomplished with the use of protocols that aggressively promote early EN, and will result in lower mortality and a reduction in major complications. Though the complexity of the heterogeneous critically ill population will always be challenging, we are developing a better understanding of immunity, metabolic needs and catabolism associated with intensive care unit admissions. PMID- 26544878 TI - Basics in Clinical Medical Nutrition. AB - Nutrition is a basic requirement for life and plays an important role in health and in disease prevention, but malnutrition is a common event and a cause of increased morbidity and mortality, particularly in patients with disease-related malnutrition showing inflammation and a catabolic state. Malnutrition is often overlooked, and deterioration in the nutritional status following admission to hospital is common. It should be actively pursued by a ubiquitous system of nutrition screening, and full nutritional assessment is required for those found to be at risk. There are simple screening tools which can be used by all health care professionals. Assessment considers body composition, inflammatory status and other aspects of underlying diseases and their functional consequences; it is a more specialist process. It is important to determine the energy and protein needs of each individual patient. Appropriate nutritional intervention can often be offered by the oral route, using food with or without special supplements. When this is insufficient, enteral tube feeding will normally be sufficient, but there is an important subgroup of patients in whom enteral feeding is contraindicated or unsuccessful, and in these patients parenteral nutrition (either total or supplemental) is required. A number of immunonutrients and other special substrates have been shown to be helpful in specific circumstances, but their use is not without potential hazards, and therefore adherence to international guidelines is recommended. PMID- 26544879 TI - Linear Augmentation for Stabilizing Stationary Solutions: Potential Pitfalls and Their Application. AB - Linear augmentation has recently been shown to be effective in targeting desired stationary solutions, suppressing bistablity, in regulating the dynamics of drive response systems and in controlling the dynamics of hidden attractors. The simplicity of the procedure is the main highlight of this scheme but questions related to its general applicability still need to be addressed. Focusing on the issue of targeting stationary solutions, this work demonstrates instances where the scheme fails to stabilize the required solutions and leads to other complicated dynamical scenarios. Examples from conservative as well as dissipative systems are presented in this regard and important applications in dissipative predator-prey systems are discussed, which include preventative measures to avoid potentially catastrophic dynamical transitions in these systems. PMID- 26544880 TI - Depletion of CG-Specific Methylation in Mycoplasma hyorhinis Genomic DNA after Host Cell Invasion. AB - Adaptation to the environment requires pathogenic bacteria to alter their gene expression in order to increase long-term survival in the host. Here, we present the first experimental evidence that bacterial DNA methylation affects the intracellular survival of pathogenic Mycoplasma hyorhinis. Using bisulfite sequencing, we identified that the M. hyorhinis DNA methylation landscape was distinct in free-living M. hyorhinis relative to the internalized bacteria surviving in the infected human cells. We determined that genomic GATC sites were consistently highly methylated in the bacterial chromosome suggesting that the bacterial GATC-specific 5-methylcytosine DNA methyltransferase was fully functional both pre- and post-infection. In contrast, only the low CG methylation pattern was observed in the mycoplasma genome in the infective bacteria that invaded and then survived in the host cells. In turn, two distinct populations, with either high or low CG methylation, were detected in the M. hyorhinis cultures continually grown in the rich medium independently of host cells. We also identified that M. hyorhinis efficiently evaded endosomal degradation and uses exocytosis to exit infected human cells enabling re-infection of additional cells. The well-orchestrated changes in the chromosome methylation landscape play a major regulatory role in the mycoplasma life cycle. PMID- 26544882 TI - The Risks of Living Kidney Donation. PMID- 26544881 TI - Host and Symbiont Jointly Control Gut Microbiota during Complete Metamorphosis. AB - Holometabolous insects undergo a radical anatomical re-organisation during metamorphosis. This poses a developmental challenge: the host must replace the larval gut but at the same time retain symbiotic gut microbes and avoid infection by opportunistic pathogens. By manipulating host immunity and bacterial competitive ability, we study how the host Galleria mellonella and the symbiotic bacterium Enterococcus mundtii interact to manage the composition of the microbiota during metamorphosis. Disenabling one or both symbiotic partners alters the composition of the gut microbiota, which incurs fitness costs: adult hosts with a gut microbiota dominated by pathogens such as Serratia and Staphylococcus die early. Our results reveal an interaction that guarantees the safe passage of the symbiont through metamorphosis and benefits the resulting adult host. Host-symbiont "conspiracies" as described here are almost certainly widespread in holometobolous insects including many disease vectors. PMID- 26544883 TI - Global Profiling of Carbohydrate Active Enzymes in Human Gut Microbiome. AB - MOTIVATION: Carbohydrate Active enzyme (CAZyme) families, encoded by human gut microflora, play a crucial role in breakdown of complex dietary carbohydrates into components that can be absorbed by our intestinal epithelium. Since nutritional wellbeing of an individual is dependent on the nutrient harvesting capability of the gut microbiome, it is important to understand how CAZyme repertoire in the gut is influenced by factors like age, geography and food habits. RESULTS: This study reports a comprehensive in-silico analysis of CAZyme profiles in the gut microbiomes of 448 individuals belonging to different geographies, using similarity searches of the corresponding gut metagenomic contigs against the carbohydrate active enzymes database. The study identifies a core group of 89 CAZyme families that are present across 85% of the gut microbiomes. The study detects several geography/age-specific trends in gut CAZyme repertoires of the individuals. Notably, a group of CAZymes having a positive correlation with BMI has been identified. Further this group of BMI associated CAZymes is observed to be specifically abundant in the Firmicutes phyla. One of the major findings from this study is identification of three distinct groups of individuals, referred to as 'CAZotypes', having similar CAZyme profiles. Distinct taxonomic drivers for these CAZotypes as well as the probable dietary basis for such trends have also been elucidated. The results of this study provide a global view of CAZyme profiles across individuals of various geographies and age-groups. These results reiterate the need of a more precise understanding of the role of carbohydrate active enzymes in human nutrition. PMID- 26544884 TI - Priming Gestures with Sounds. AB - We report a series of experiments about a little-studied type of compatibility effect between a stimulus and a response: the priming of manual gestures via sounds associated with these gestures. The goal was to investigate the plasticity of the gesture-sound associations mediating this type of priming. Five experiments used a primed choice-reaction task. Participants were cued by a stimulus to perform response gestures that produced response sounds; those sounds were also used as primes before the response cues. We compared arbitrary associations between gestures and sounds (key lifts and pure tones) created during the experiment (i.e. no pre-existing knowledge) with ecological associations corresponding to the structure of the world (tapping gestures and sounds, scraping gestures and sounds) learned through the entire life of the participant (thus existing prior to the experiment). Two results were found. First, the priming effect exists for ecological as well as arbitrary associations between gestures and sounds. Second, the priming effect is greatly reduced for ecologically existing associations and is eliminated for arbitrary associations when the response gesture stops producing the associated sounds. These results provide evidence that auditory-motor priming is mainly created by rapid learning of the association between sounds and the gestures that produce them. Auditory motor priming is therefore mediated by short-term associations between gestures and sounds that can be readily reconfigured regardless of prior knowledge. PMID- 26544885 TI - Age-Related Relationships between Innate Immunity and Plasma Carotenoids in an Obligate Avian Scavenger. AB - Variation in immunity is influenced by allocation trade-offs that are expected to change between age-classes as a result of the different environmental and physiological conditions that individuals encounter over their lifetime. One such trade-off occurs with carotenoids, which must be acquired with food and are involved in a variety of physiological functions. Nonetheless, relationships between immunity and carotenoids in species where these micronutrients are scarce due to diet are poorly studied. Among birds, vultures show the lowest concentrations of plasma carotenoids due to a diet based on carrion. Here, we investigated variations in the relationships between innate immunity (hemagglutination by natural antibodies and hemolysis by complement proteins), pathogen infection and plasma carotenoids in nestling and adult griffon vultures (Gyps fulvus) in the wild. Nestlings showed lower hemolysis, higher total carotenoid concentration and higher pathogen infection than adults. Hemolysis was negatively related to carotenoid concentration only in nestlings. A differential carotenoid allocation to immunity due to the incomplete development of the immune system of nestlings compared with adults is suggested linked to, or regardless of, potential differences in parasite infection, which requires experimental testing. We also found that individuals with more severe pathogen infections showed lower hemagglutination than those with a lower intensity infection irrespective of their age and carotenoid level. These results are consistent with the idea that intraspecific relationships between innate immunity and carotenoids may change across ontogeny, even in species lacking carotenoid-based coloration. Thus, even low concentrations of plasma carotenoids due to a scavenger diet can be essential to the development and activation of the immune system in growing birds. PMID- 26544886 TI - Distribution of brominated flame retardants and dechloranes between sediments and benthic fish--A comparison of a freshwater and marine habitat. AB - A total of 53 halogenated flame retardants (HFRs) were analysed in sediments, European eels and dabs from both freshwater and marine sampling stations in the German Bight and the river Elbe. Classic HFRs, such as polybrominated diphenylethers (PBDEs), were the highest concentrated HFRs in eels as well as in most dabs (apart from 1,2,5,6-tetrabromocyclooctane (TBCO)). In sediments, on the other hand, alternate BFRs and especially dechloranes dominated the contamination pattern. Dabs were still found to be statistically representative for the contamination patterns and relative magnitude in sediments from their respective habitats. Contamination patterns in eels seemed to be more driven by the contamination situation in the food chain or historical contamination of their habitat. Unsuspectedly the alternate flame retardant TBCO was found in comparably high concentrations (up to 12 ng g(-1) ww) in dabs from two sampling stations as well as in sediments from these stations (up to 1.2 ng g(-1) dw). It could not be detected in any other analysed fish or sediment samples, indicating a localised contamination source in the area. This study provides information on HFR contamination patterns and behaviour in both marine and freshwater sediments and their potential role as contamination source for benthic fish. PMID- 26544887 TI - The 2014 water release into the arid Colorado River delta and associated water losses by evaporation. AB - For the first time in history, water was intentionally released for environmental purposes into the final, otherwise dry, 160-km stretch of the Colorado River basin, south of the Mexican border. Between March and May 2014 three pulses of water with a total volume of 132*10(6) m(3) were released to assess the restoration potential of endemic flora along its course and to reach its estuary. The latter had not received a sustained input of fresh water and nutrients from its main fluvial source for over 50 years because of numerous upstream dam constructions. During this pulse flow large amounts of water were lost and negligible amounts reached the ocean. While some of these water losses can be attributed to plant uptake and infiltration, we were able to quantify evaporation losses between 16.1 to 17.3% of the original water mass % within the first 80 km after the Morels Dam with water stable isotope data. Our results showed no evidence for freshwater reaching the upper Colorado River estuary and it is assumed that the pulse flow had only negligible influences on the coastal ecosystem. Future water releases that aim on ecological restoration need to become more frequent and should have larger volumes if more significant effects are to be established on the area. PMID- 26544888 TI - Seed banks as a source of vegetation regeneration to support the recovery of degraded rivers: A comparison of river reaches of varying condition. AB - Anthropogenic disturbance has contributed to widespread geomorphic adjustment and the degradation of many rivers. This research compares for river reaches of varying condition, the potential for seed banks to support geomorphic river recovery through vegetation regeneration. Seven river reaches in the lower Hunter catchment of south-eastern Australia were assessed as being in poor, moderate, or good condition, based on geomorphic and ecological indicators. Seed bank composition within the channel and floodplain (determined in a seedling emergence study) was compared to standing vegetation. Seed bank potential for supporting geomorphic recovery was assessed by measuring native species richness, and the abundance of different plant growth forms, with consideration of the roles played by different growth forms in geomorphic adjustment. The exotic seed bank was considered a limiting factor for achieving ecological restoration goals, and similarly analysed. Seed bank native species richness was comparable between the reaches, and regardless of condition, early successional and pioneer herbs, sedges, grasses and rushes dominated the seed bank. The capacity for these growth forms to colonise and stabilise non-cohesive sediments and initiate biogeomorphic succession, indicates high potential for the seed banks of even highly degraded reaches to contribute to geomorphic river recovery. However, exotic propagules increasingly dominated the seed banks of moderate and poor condition reaches and reflected increasing encroachment by terrestrial exotic vegetation associated with riparian degradation. As the degree of riparian degradation increases, the resources required to control the regeneration of exotic species will similarly increase, if seed bank-based regeneration is to contribute to both geomorphic and ecological restoration goals. PMID- 26544889 TI - A breakthrough biosorbent in removing heavy metals: Equilibrium, kinetic, thermodynamic and mechanism analyses in a lab-scale study. AB - A breakthrough biosorbent namely multi-metal binding biosorbent (MMBB) made from a combination of tea wastes, maple leaves and mandarin peels, was prepared to evaluate their biosorptive potential for removal of Cd(II), Cu(II), Pb(II) and Zn(II) from multi-metal aqueous solutions. FTIR and SEM were conducted, before and after biosorption, to explore the intensity and position of the available functional groups and changes in adsorbent surface morphology. Carboxylic, hydroxyl and amine groups were found to be the principal functional groups for the sorption of metals. MMBB exhibited best performance at pH 5.5 with maximum sorption capacities of 31.73, 41.06, 76.25 and 26.63 mg/g for Cd(II), Cu(II), Pb(II) and Zn(II), respectively. Pseudo-first and pseudo-second-order models represented the kinetic experimental data in different initial metal concentrations very well. Among two-parameter adsorption isotherm models, the Langmuir equation gave a better fit of the equilibrium data. For Cu(II) and Zn(II), the Khan isotherm describes better biosorption conditions while for Cd(II) and Pb(II), the Sips model was found to provide the best correlation of the biosorption equilibrium data. The calculated thermodynamic parameters indicated feasible, spontaneous and exothermic biosorption process. Overall, this novel MMBB can effectively be utilized as an adsorbent to remove heavy metal ions from aqueous solutions. PMID- 26544890 TI - Inadequacy of carbamazepine-spiked model wastewaters for testing photocatalysis efficiency. AB - The study was performed in order to clarify whether carbamazepine-spiked solutions used as model wastewaters are suitable for the assessment of carbamazepine removal from real secondary municipal effluents by photocatalytic oxidation in the presence and absence of activated carbon. Therefore, carbamazepine (10 mg L(-1)) was dissolved in deionized water or in secondary municipal effluent. Photocatalytic oxidation of these model wastewaters was carried out with TiO2 "P25" (100 mg L(-1)) and UV-A lamps in the absence and in the presence of 20 mg L(-1) powdered activated carbon (PAC). Carbamazepine was analyzed photometrically. In deionized water at pH 5.5, carbamazepine was nearly completely removed with a UV dose of 6.48 kJ L(-1). A similar efficiency of photocatalytic oxidation of carbamazepine added to secondary effluent was observed when the suspension pH was 2.7, while at pH 8 and 10.6, carbamazepine removal from spiked secondary effluent with the same UV dose was only 40 and 60%, respectively. Although PAC addition resulted in an initial adsorptive carbamazepine reduction of 20 to 35% from the model wastewaters, it did not lead to markedly enhanced carbamazepine removal in the subsequent photocatalysis phase. During photocatalytic oxidation of unspiked secondary effluent (initial carbamazepine concentration: 133 ng L(-1)) at pH 7.3 with and without PAC, carbamazepine concentrations were analyzed by HPLC/MS/MS. While PAC addition resulted in the adsorption of about 90% of the initial carbamazepine, photocatalysis did not lead to any carbamazepine removal at all. This indicates that the experiments with spiked model wastewaters - even in a secondary effluent matrix - are absolutely inadequate for predicting photocatalytic carbamazepine removal under real conditions. PMID- 26544891 TI - Pesticides in persimmons, jujubes and soil from China: Residue levels, risk assessment and relationship between fruits and soils. AB - Extreme and uncontrolled usage of pesticides produces a number of problems for vegetation and human health. In this study, the existence of organophosphates (OPs), organochlorines (OCs), pyrethroids (PYs) and fungicides (FUs) were investigated in persimmons/jujubes and their planted soils, which were collected from China. One OP (dimethoate), three OCs (DDT, quintozene and aldrin), six PYs (bifenthrin, fenpropathrin, cyhalothrin, cypermethrin, fenvalerate and deltamethrin) and two FUs (triadimefon and buprofezin) were found in 36.4% of persimmons and 70.8% of jujubes, with concentrations from 1.0 MUg/kg to 2945.0 MUg/kg. The most frequently detected pesticides in the two fruits were fenpropathrin in persimmons and cypermethrin in jujubes, with the detection frequencies of 30.0% and 22.7%, respectively. The residues of 4.5% (persimmon) and 25.0% (jujube) of samples were higher than the maximum residue limits (MRLs) of China. Compared with the fruits, more types of pesticides and higher residues were observed in their planted soils. The most frequently detected pesticides were HCH in persimmon soil and DDT in jujube soil, with the detection frequencies of 10.9% and 12.7%, respectively. For the tested samples, 39.1% of fruit samples and 63.0% of soil samples with multiple residues (containing more than two pesticides) were noted, even up to 8 residues in fruits and 14 residues in soils. Except for cyhalothrin, the other short-term risks for the tested pesticides in the fruits were below 10%, and the highest long-term risk was 14.13% for aldrin and dieldrin. There was no significant health risk for consumers via consumption of the two fruits. PMID- 26544892 TI - Efflorescent sulfates from Baia Sprie mining area (Romania)--Acid mine drainage and climatological approach. AB - The Baia Sprie epithermal system, a well-known deposit for its impressive mineralogical associations, shows the proper conditions for acid mine drainage and can be considered a general example for affected mining areas around the globe. Efflorescent samples from the abandoned open pit Minei Hill have been analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman and near-infrared (NIR) spectrometry. The identified phases represent mostly iron sulfates with different hydration degrees (szomolnokite, rozenite, melanterite, coquimbite, ferricopiapite), Zn and Al sulfates (gunningite, alunogen, halotrichite). The samples were heated at different temperatures in order to establish the phase transformations among the studied sulfates. The dehydration temperatures and intermediate phases upon decomposition were successfully identified for each of mineral phases. Gunningite was the single sulfate that showed no transformations during the heating experiment. All the other sulfates started to dehydrate within the 30-90 degrees C temperature range. The acid mine drainage is the main cause for sulfates formation, triggered by pyrite oxidation as the major source for the abundant iron sulfates. Based on the dehydration temperatures, the climatological interpretation indicated that melanterite formation and long-term presence is related to continental and temperate climates. Coquimbite and rozenite are attributed also to the dry arid/semi-arid areas, in addition to the above mentioned ones. The more stable sulfates, alunogen, halotrichite, szomolnokite, ferricopiapite and gunningite, can form and persists in all climate regimes, from dry continental to even tropical humid. PMID- 26544893 TI - Genetic and epigenetic characterization of hypodiploid acute lymphoblastic leukemia. AB - PURPOSE: To investigate the genetic and epigenetic landscape of hypodiploid (<45 chromosomes) acute lymphoblastic leukemia (ALL). METHODS: Single nucleotide polymorphism array, whole exome sequencing, RNA sequencing, and methylation array analyses were performed on eleven hypodiploid ALL cases. RESULTS: In line with previous studies, mutations in IKZF3 and FLT3 were detected in near-haploid (25 30 chromosomes) cases. Low hypodiploidy (31-39 chromosomes) was associated with somatic TP53 mutations. Notably, mutations of this gene were also found in 3/3 high hypodiploid (40-44 chromosomes) cases, suggesting that the mutational patterns are similar in low hypodiploid and high hypodiploid ALL. The high hypodiploid ALLs frequently displayed substantial cell-to-cell variability in chromosomal content, indicative of chromosomal instability; a rare phenomenon in ALL. Gene expression analysis showed that genes on heterodisomic chromosomes were more highly expressed in hypodiploid cases. Cases clustered according to hypodiploid subtype in the unsupervised methylation analyses, but there was no association between chromosomal copy number and methylation levels. A comparison between samples obtained at diagnosis and relapse showed that the relapse did not arise from the major diagnostic clone in 3/4 cases. CONCLUSIONS: Taken together, our data support the conclusion that near-haploid and low hypodiploid ALL are different with regard to mutational profiles and also suggest that ALL cases with high hypodiploidy may harbor chromosomal instability. PMID- 26544894 TI - Predictive significance of DNA damage and repair biomarkers in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: An exploratory analysis. AB - Response of cancer cells to chemotherapy-induced DNA damage is regulated by the ATM-Chk2 and ATR-Chk1 pathways. We investigated the association between phosphorylated H2AX (gamma-H2AX), a marker of DNA double-strand breaks that trigger the ATM-Chk2 cascade, and phosphorylated Chk1 (pChk1), with pathological complete response (pCR) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy. gamma-H2AX and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 patients. In fifty-three tumors hormone receptor status was negative in both the diagnostic biopsies and residual cancers, whereas in 13 cases there was a slight hormone receptor expression that changed after chemotherapy. Internal validation was carried out. In the entire cohort elevated levels of gamma-H2AX, but not pChk1, were associated with reduced pCR rate (p = 0.009). The association tested significant in both uni- and multivariate logistic regression models (OR 4.51, 95% CI: 1.39-14.66, p = 0.012, and OR 5.07, 95% CI: 1.28-20.09, p = 0.021, respectively). Internal validation supported the predictive value of the model. The predictive ability of gamma-H2AX was further confirmed in the multivariate model after exclusion of tumors that underwent changes in hormone receptor status during chemotherapy (OR 7.07, 95% CI: 1.39-36.02, p = 0.018). Finally, in residual diseases a significant decrease of gamma-H2AX levels was observed (p < 0.001). Overall, gamma-H2AX showed ability to predict pCR in TNBC and deserves larger, prospective studies. PMID- 26544895 TI - Mutant GDF15 presents a poor prognostic outcome for patients with oral squamous cell carcinoma. AB - PURPOSE: To investigate the mutation status of growth differentiation factor 15 (GDF15) in patients with oral squamous cell carcinoma (OSCC), as well as the prognostic value of missense GDF15 mutations. PATIENTS AND METHODS: Formalin fixed paraffin-embedded biopsy samples from 46 OSCC patients were involved in this study. GDF15 and TP53 mutations were sequenced using the Ion Torrent Personal Genome Machine, GDF15 protein expression was detected using immunohistochemistry. Torrent Suite Software v.3.6, Integrative Genomics Viewer; v.2.3, statistical software SPSS18.0 for Windows were used for analysis. All hypothesis-generating tests were two-sided at a significance level of 0.05. RESULTS: Twenty-nine GDF15 mutations were identified in 19 out of 46 patients (41.3%), including eighteen missense mutations, two nonsense mutations and nine synonymous mutations. The patients with missense GDF15 mutations had poorer prognostic outcomes than those with wild-type GDF15, including overall survival (P = 0.035), disease-free survival (P = 0.032), locoregional recurrence-free survival (P = 0.015), and distant metastasis-free survival (P = 0.070). Missense GDF15mutations was an independent increased risk factor of overall survival (HR = 5.993, 95% CI:1.856-19.346, P = 0.003), disease-free survival (HR = 3.764, 95% CI:1.295-10.945, P = 0.015), locoregional recurrence-free survival (HR = 4.555, 95% CI:1.494-13.889, P = 0.008), and distant metastasis-free survival (HR = 4.420, 95% CI:1.145-13.433, P = 0.009). CONCLUSIONS: Patients with missense GDF15 mutations have significantly poorer outcomes than those with wild-type GDF15, missense GDF15 mutations could be used as an independent increased risk factor of poor prognosis in OSCC patients. PMID- 26544896 TI - GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma. AB - While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N acetylgalactosaminyltransferase (GalNAc-T14), is highly inversely correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here, we showed that GalNAc-T14 expression was positively associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9, the expression of which was increased in a GalNAc-T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the beta-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of beta-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival and increased hazard risk, suggesting that targeting beta-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC. PMID- 26544898 TI - The impact of serotonin receptor 1A and 2A gene polymorphisms and interactions on suicide attempt and suicide risk in depressed patients with insufficient response to treatment--a European multicentre study. AB - So far, associations between serotonergic neurotransmission pathways and suicidality have been reported. The aim of our study was to investigate the role of genetic polymorphisms and gene-gene interactions of the 5-HTR1A and the 5 HTR2A gene on suicide risk and/or a personal history of suicide attempts. A total of 374 major depressive disorder patients, adequately treated with antidepressants for at least 4 weeks, were collected in the context of a European multicentre study on treatment-resistant depression. We assessed suicidality using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D <= 17 and remission as HAM-D <= 7 after 4 weeks of adequate antidepressant treatment. The 5 HTR1A rs6295 (C-1019G) single nucleotide polymorphism (SNP) and the 5-HTR2A rs7997012, rs6313, rs643627 and rs17288723 SNPs were selected for genotyping. Using logistic regression analyses, no association (P<0.05) could be found between any SNP and neither suicide risk nor personal history of suicide attempts. Interactions between 5HTR1A rs6295 and 5HTR2A rs6313 in suicide risk, and 5HTR1A rs6295 and 5HTR2A rs643627 in a personal history of suicide attempts have been reported (P=0.027 and 0.036, respectively); however, the results did not survive multiple testing correction. In conclusion, our study shows no association between 5HTR1A or 5HTR2A gene polymorphisms and both current suicide risk and personal history of suicide attempts. In addition, epistatic effects of 5HTR1A and 5HTR2A genes on suicidal behaviour were not significant, although sample size limitations do not allow definitive conclusions. PMID- 26544897 TI - 5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53. AB - Despite recent advances in targeted therapeutics, administration of 5 fluorouracil (5-FU) remains a common clinical strategy for post-surgical treatment of solid tumors. Although it has been proposed that RNA metabolism is disturbed by 5-FU treatment, the key cytotoxic response is believed to be enzymatic inhibition of thymidylate synthase resulting in nucleotide pool disproportions. An operating p53 tumor suppressor signaling network is in many cases essential for the efficiency of chemotherapy, and malfunctions within this system remain a clinical obstacle. Since the fate of chemotherapy-insensitive tumor cells is rarely described, we performed a comparative analysis of 5-FU toxicity in p53-deficient cells and conclude that p53 acts as a facilitator rather than a gatekeeper of cell death. Although p53 can act as a regulator of several cellular stress responses, no rerouting of cell death mode was observed in absence of the tumor suppressor. Thus, the final death outcome of 5-FU-treated p53-/- cells is demonstrated to be caspase-dependent, but due to a slow pace, accumulation of mitochondrial reactive oxygen species contributes to necrotic characteristics. The oligomerization status of the p53 target gene DR5 is determined as a significant limiting factor for the initiation of caspase activity in an intracellular TRAIL-dependent manner. Using several experimental approaches, we further conclude that RNA-rather than DNA-related stress follows by caspase activation irrespectively of p53 status. A distinct 5-FU-induced stress mechanism is thereby functionally connected to a successive and discrete cell death signaling pathway. Finally, we provide evidence that silencing of PARP 1 function may be an approach to specifically target p53-deficient cells in 5-FU combinatorial treatment strategies. Together, our results disclose details of impaired cell death signaling engaged as a consequence of 5-FU chemotherapy. Obtained data will contribute to the comprehension of factors restraining 5-FU efficiency, and by excluding DNA as the main stress target in some cell types they propose alternatives to currently used and suggested synergistic treatment regimens. PMID- 26544899 TI - Stimulant medication effects on growth and bone age in children with attention deficit/hyperactivity disorder: a prospective cohort study. AB - Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7-5.5, vs. 6.3 cm/year, 95% CI: 5.7-6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1-3.3, vs. 4.4 kg/year, 95% CI: 3.5-5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44-55, vs. 55 U/year, 95% CI: 47-63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61+/-3.56-4.22+/-3.09 kg, P<0.001) and leptin (3.88+/-2.87-2.57+/-1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex). PMID- 26544900 TI - CYP2C9 variants as a risk modifier of NSAID-related gastrointestinal bleeding: a case-control study. AB - OBJECTIVE: The aim of this study was to assess whether the CYP2C9*2 and/or *3 variants might modify the risk for NSAID-related upper gastrointestinal bleeding (UGIB) in NSAID users. PATIENTS AND METHODS: We conducted a multicenter, case control study in which cases were patients aged more than 18 years with a diagnosis of UGIB, and controls were matched (1 : 3) by sex, age, date of admission, and hospital. Exposure was defined as the mean number of defined daily doses (DDDs) of NSAIDs metabolized by CYP2C9 in the week preceding the index date. Three DDD categories were defined (0, <= 0.5, and > 0.5). Exposure was constructed taking both NSAID use and CYP2C9 polymorphisms into account. Patients of non-European origin were excluded from the analysis. RESULTS: A total of 577 cases and 1343 controls were finally included in the analysis: 103 cases and 89 controls consumed NSAIDs metabolized by CYP2C9, and 88 cases and 177 controls were CYP2C9*3 carriers. The adjusted odds ratios (aORs) of UGIB associated with the CYP2C9*2 and wild-type alleles proved to be similar [OR=8.79 (4.50-17.17) and 10.15 (2.92-35.35), respectively] and lower than those of the CYP2C9*3 allele [aOR=18.07 (6.34-51.53)] for consumers taking more than 0.5 DDDs of NSAIDs metabolized by CYP2C9. Grouping genotypes into carriers and noncarriers of the CYP2C9*3 variant resulted in aORs of 16.92 (4.96-57.59) for carriers and 9.72 (4.55-20.76) for noncarriers, where DDDs were greater than 0.5. CONCLUSION: The presence of the CYP2C9*3 variant increases the risk for UGIB associated with NSAID for DDDs greater than 0.5. The presence of the CYP2C9*2 allele shows no such effect. PMID- 26544901 TI - Human health benefits and burdens of a pharmaceutical treatment: Discussion of a conceptual integrated approach. AB - The effects of a pharmaceutical treatment have until now been evaluated by the field of Health Economics on the patient health benefits, expressed in Quality Adjusted Life Years (QALYs) versus the monetary costs. However, there is also a Human Health burden associated with this process, resulting from emissions that originate from the pharmaceutical production processes, Use Phase and End of Life (EoL) disposal of the medicine. This Human Health burden is evaluated by the research field of Life Cycle Assessment (LCA) and expressed in Disability Adjusted Life Years (DALYs), a metric similar to the QALY. The need for a new framework presents itself in which both the positive and negative health effects of a pharmaceutical treatment are integrated into a net Human Health effect. To do so, this article reviews the methodologies of both Health Economics and the area of protection Human Health of the LCA methodology and proposes a conceptual framework on which to base an integration of both health effects. Methodological issues such as the inclusion of future costs and benefits, discounting and age weighting are discussed. It is suggested to use the structure of an LCA as a backbone to cover all methodological challenges involved in the integration. The possibility of monetizing both Human Health benefits and burdens is explored. The suggested approach covers the main methodological aspects that should be considered in an integrated assessment of the health effects of a pharmaceutical treatment. PMID- 26544902 TI - Unusual appearance for urinary bladder obstruction detected with 99mTc-MDP bone scintigraphy. AB - Unanticipated but clinically significant nonosseous findings can be detected during routine bone scintigraphy. We present a case of an 83-year-old man who presented with a pathologic fracture of the right femur. Whole-body bone scintigraphy for osseous staging revealed intense radiotracer accumulation in the kidneys and ureters but no activity within the urinary bladder. The patient had not voided for 14 hours. A Foley catheter was inserted, and more than 2000 mL of urine was drained, most consistent with urinary bladder obstruction. Subsequent repeat images demonstrated marked reduction of the renal and ureteral activity with trace activity in the urinary bladder. PMID- 26544903 TI - Weak uptake of 123I-MIBG and 18F-FDOPA contrasting with high 18F-FDG uptake in stage I neuroblastoma. AB - Hypertension in a 6-year-old girl was the presenting sign of a stage I neuroblastoma. This tumor corresponded to a left adrenal gland mass. Hypertension resolved immediately after complete surgical resection of the tumor with an uneventful follow-up (24 months at the present time). Preoperative assessment by nuclear medicine techniques showed weak uptake of I-MIBG and F-FDOPA contrasting with high F-FDG uptake by the tumor. PMID- 26544904 TI - MRI and FDG PET/CT imaging manifestations of cardiac sarcoidosis. AB - A 52-year-old man had biopsy-proven sarcoidosis of mediastinal lymph nodes. Cardiac sarcoidosis was confirmed on cardiac MRI with typical imaging features as delayed gadolinium enhancement. Follow-up FDG PET/CT with a 3-day pretest diet modification showed suppression of overall myocardial uptake of FDG but with multifocal abnormal FDG uptake in the myocardium regions corresponding to the previous MRI findings. Additional noncardiac active sarcoidosis involving multiple organ and lymph nodes were also visualized on FDG PET/CT. PMID- 26544905 TI - Corrigendum to "magnetic resonance imaging in neonatal encephalopathy" [Early Hum. Dev. 81 (1) (2005 Jan) 13-25]. PMID- 26544906 TI - Cognitive and language performance in children is associated with maternal social anxiety disorder: A study of young mothers in southern Brazil. AB - BACKGROUND: It has been shown that maternal mental health is associated with poorer skills development in the offspring. However, the evidence evaluating the association between social anxiety disorder (SAD) and cognitive or language development, is scarce. AIM: To evaluate the association between maternal SAD and performance in cognitive and language tests in 30-month old children. STUDY DESIGN: This was a cohort study involving young women evaluated since pregnancy. SUBJECTS: We evaluated 520 mother-child dyads who received prenatal medical assistance through the National Public Health System in a southern Brazilian city, from October 2009 to March 2011. OUTCOME MEASURES: We used the Mini Neuropsychiatric Interview Plus (MINI Plus) to assess SAD among young mothers. Cognitive and language performance in their offspring was analyzed using the Bayley Scales of Infant and Toddler Development - 3rd Edition. RESULTS: We found an association between maternal SAD and performance in cognitive and language tests. Children of mothers with SAD had in average 4.5 less points in the Bayley scale, when compared to those with mothers without SAD: in the cognitive (beta= 4.53 [95% CI -7.8; -1.1] p=0.008) and language subscales (beta=-4.54 [95% CI 9.0; -0.5] p=0.047). CONCLUSIONS: Our findings suggest that children with mothers suffering from SAD have poorer cognitive abilities and language skills. PMID- 26544907 TI - The Microbiota and Transgenomic Networks: Potential Implications for Maternal Fetal Medicine. AB - The maternal microbiota has long been considered a potential cause for adverse perinatal outcomes. Gene expression regulators in prokaryotic and eukaryotic cells are influenced by changes in their microenvironments. We propose the novel idea that during in utero development, an adaptive and dynamic gene-regulatory cross talk might exist between the host genome and the maternal microbiota. Understanding these cross talks could increase the appreciation for the discovery of new diagnostics and therapeutics in maternal-fetal medicine. PMID- 26544908 TI - Video-assisted thoracic surgery (VATS) segmentectomy: state of the art. AB - The role of video-assisted thoracic surgery (VATS) in the treatment of lung cancer is well established. However a topic of current debate centers on the role of parenchymal-sparing operations, segmentectomy in particular, in the treatment of non-small cell lung cancer (NSCLC). Current reports in the literature draw dramatically different conclusions regarding the efficacy and safety of segmentectomy versus lobectomy for NSCLC. Two randomized controlled trials are currently underway to shed further light on this topic. Lobectomy remains the standard of care, with VATS approaches demonstrating improved morbidity. Experience in literature suggests segmentectomy is a viable approach for patients with limited cardiopulmonary reserve, or who would otherwise be unable to tolerate lobectomy. Thus, VATS segmentectomy is a vital skill in the armamentarium of today's thoracic surgeon. Minimally invasive approaches to segmentectomy are accomplished with a certain amount of finesse and a thorough understanding of the associated anatomy. A technical description of VATS segmentectomy is provided. PMID- 26544909 TI - Method for Sorting and Pairwise Selection of Nanobodies for the Development of Highly Sensitive Sandwich Immunoassays. AB - Single domain heavychain binders (nanobodies) obtained from camelid antibody libraries hold a great promise for immunoassay development. However, there is no simple method to select the most valuable nanobodies from the crowd of positive clones obtained after the initial screening. In this paper, we describe a novel nanobody-based platform that allows comparison of the reactivity of hundreds of clones with the labeled antigen, and identifies the best nanobody pairs for two site immunoassay development. The output clones are biotinylated in vivo in 96 well culture blocks and then used to saturate the biotin binding capacity of avidin coated wells. This standardizes the amount of captured antibody allowing their sorting by ranking their reactivity with the labeled antigen. Using human soluble epoxide hydrolase (sEH) as a model antigen, we were able to classify 96 clones in four families and confirm this classification by sequencing. This provided a criterion to select a restricted panel of five capturing antibodies and to test each of them against the rest of the 96 clones. The method constitutes a powerful tool for epitope binning, and in our case allowed development of a sandwich ELISA for sEH with a detection limit of 63 pg/mL and four log dynamic range, which performed with excellent recovery in different tissue extracts. This strategy provides a systematic way to test nanobody pairwise combinations and would have a broad utility for the development of highly sensitive sandwich immunoassays. PMID- 26544911 TI - Average and Local Crystal Structures of (Ga(1-x)Znx)(N(1-x)Ox) Solid Solution Nanoparticles. AB - We report a comprehensive study of the crystal structure of (Ga(1-x)Znx)(N(1 x)Ox) solid solution nanoparticles by means of neutron and synchrotron X-ray scattering. In our study, we used four different types of (Ga(1-x)Znx)(N(1-x)Ox) nanoparticles, with diameters of 10-27 nm and x = 0.075-0.51, which show energy band gaps from 2.21 to 2.61 eV. Rietveld analysis of the neutron diffraction data revealed that the average crystal structure is hexagonal wurtzite (space group P63mc) for the larger nanoparticles, while the crystal structure of smaller nanoparticles is disordered hexagonal. Pair-distribution-function analysis found that the intermediate crystal structure retains a "motif" of the average one; however, the local structure is more disordered. The implications of disorder on the reduced energy band gap are discussed. PMID- 26544910 TI - Detection of RNA-Protein Interactions in Living Cells with SHAPE. AB - SHAPE-MaP is unique among RNA structure probing strategies in that it both measures flexibility at single-nucleotide resolution and quantifies the uncertainties in these measurements. We report a straightforward analytical framework that incorporates these uncertainties to allow detection of RNA structural differences between any two states, and we use it here to detect RNA protein interactions in healthy mouse trophoblast stem cells. We validate this approach by analysis of three model cytoplasmic and nuclear ribonucleoprotein complexes, in 2 min in-cell probing experiments. In contrast, data produced by alternative in-cell SHAPE probing methods correlate poorly (r = 0.2) with those generated by SHAPE-MaP and do not yield accurate signals for RNA-protein interactions. We then examine RNA-protein and RNA-substrate interactions in the RNase MRP complex and, by comparing in-cell interaction sites with disease associated mutations, characterize these noncoding mutations in terms of molecular phenotype. Together, these results reveal that SHAPE-MaP can define true interaction sites and infer RNA functions under native cellular conditions with limited preexisting knowledge of the proteins or RNAs involved. PMID- 26544912 TI - Solvolysis, Electrochemistry, and Development of Synthetic Building Blocks from Sawdust. AB - Either aldehyde or cinnamyl ether products can be selectively extracted from raw sawdust by controlling the temperature and pressure of a solvolysis reaction. These materials have been used as platform chemicals for the synthesis of 15 different synthetic substrates. The conversion of the initial sawdust-derived materials into electron-rich aryl substrates often requires the use of oxidation and reduction chemistry, and the role electrochemistry can play as a sustainable method for these transformations has been defined. PMID- 26544913 TI - Absorption Spectrum of a Ru(II)-Aquo Complex in Vacuo: Resolving Individual Charge-Transfer Transitions. AB - Ruthenium(II) complexes are of great interest as homogeneous catalysts and as photosensitizers; however, their absorption spectra are typically very broad and offer only little insight into their electronic structure. We present the electronic spectrum of the aquo complex [(trpy)(bipy)Ru(II)-OH2](2+) measured by photodissociation spectroscopy of mass-selected ions in vacuo (bipy = 2,2' bipyridine and trpy = 2,2':6',2"-terpyridine). In the visible and near-UV, [(trpy)(bipy)Ru(II)-OH2](2+) has several electronic bands that are not resolved in absorption spectra of this complex in solution but are partially resolved in vacuo. The experimental results are compared with results from time-dependent density functional theory calculations. PMID- 26544914 TI - Atomic Resolution Observation of a Size-Dependent Change in the Ripening Modes of Mass-Selected Au Nanoclusters Involved in CO Oxidation. AB - Identifying the ripening modes of supported metal nanoparticles used in heterogeneous catalysis can provide important insights into the mechanisms that lead to sintering. We report the observation of a crossover from Smoluchowski to Ostwald ripening, under realistic reaction conditions, for monomodal populations of precisely defined gold particles in the nanometer size range, as a function of decreasing particle size. We study the effects of the CO oxidation reaction on the size distributions and atomic structures of mass-selected Au(561+/-13), Au(923+/-20) and Au(2057+/-45) clusters supported on amorphous carbon films. Under the same conditions, Au(561+/-13) and Au(923+/-20) clusters are found to exhibit Ostwald ripening, whereas Au(2057+/-45) ripens through cluster diffusion and coalescence only (Smoluchowski ripening). The Ostwald ripening is not activated by thermal annealing or heating in O2 alone. PMID- 26544917 TI - Effect of Boron-Doping on the Graphene Aerogel Used as Cathode for the Lithium Sulfur Battery. AB - A porous interconnected 3D boron-doped graphene aerogel (BGA) was prepared via a one-pot hydrothermal treatment. The BGA material was first loaded with sulfur to serve as cathode in lithium-sulfur batteries. Boron was positively polarized on the graphene framework, allowing for chemical adsorption of negative polysufide species. Compared with nitrogen-doped and undoped graphene aerogel, the BGA-S cathode could deliver a higher capacity of 994 mA h g(-1) at 0.2 C after 100 cycles, as well as an outstanding rate capability, which indicated the BGA was an ideal cathode material for lithium-sulfur batteries. PMID- 26544916 TI - GLI1 expression is an important prognostic factor that contributes to the poor prognosis of rhabdomyosarcoma. AB - The GLI1 and MDM2 genes are amplified or exhibit copy number gains in rhabdomyosarcoma (RMS). Here, we used immunohistochemistry to determine the relationships between GLI1 and MDM2 protein expression and several clinicopathological variables of RMS. GLI1 and MDM2-positivity rates were 61.36% and 13.64%, respectively. GLI1 expression correlated with presence of the PAX3 FOXO1 fusion gene (P=0.040) and lymph node metastasis (P=0.034), and a significant association was found between GLI1 expression and overall survival (OS) (P=0.008). However, there was no association between MDM2 expression and any of the clinicopathological parameters or OS. Thus, GLI1 may be a biomarker of poor prognosis in RMS patients, and could itself be a therapeutic target. This contrasts with the apparent lack of clinical importance of MDM2 in RMS pathology, at least in the cohorts we examined. PMID- 26544915 TI - The Role of Depression in Retention in Care for Persons Living with HIV. AB - Individuals infected with HIV experience high rates of depression when compared to their sero-negative counterparts. Although symptoms of depression have been consistently linked to poor medication adherence among persons living with HIV/AIDS, their relation to retention in care are less well-known. The purpose of this study was to examine whether clusters of depressive symptoms influence retention in care and if so, whether these clusters had different relations to retention in care. This is a secondary data analysis of a larger study that investigated the role of health literacy, cognitive impairment, and social determinants on retention in HIV care. Individuals with HIV were recruited from South Florida from August 2009 to May 2011. A total of 210 participants were included in the current analyses. A measure of visit constancy was calculated to represent the number of 4-month intervals with at least one kept visit. Individual items on the Center for Epidemiological Studies Depression Scale short form (CES-D10) and factor analysis of the CES-D10 were independent variables. Overall, there was a high prevalence of depressive symptoms in the study participants. Furthermore, factor analysis showed that certain clusters of depressive symptoms were significantly associated with visit constancy. Specifically, negative mood/somatic symptoms were associated with a greater odds of missing a visit in any of the observed 4-month time periods than positive mood factor. Those patients reporting somatic symptoms and negative mood may need additional intervention and support to be effectively retained in care and successfully follow through with appointments and care. PMID- 26544918 TI - Hemispheric Specialization within the Superior Anterior Temporal Cortex for Social and Nonsocial Concepts. AB - Studies of semantic dementia, imaging, and repetitive TMS have suggested that the bilateral anterior temporal lobes (ATLs) underpin a modality-invariant representational hub within the semantic system. Questions remain, however, regarding functional specialization across a variety of knowledge domains within the ATL region. We investigated direct evidence for the functional relevance of the superior ATL in processing social concepts. Using converging evidence from noninvasive brain stimulation and neuropsychology, we demonstrate graded differentiation of right and left superior anterior temporal areas in social cognition. Whereas the left superior ATL is necessary for processing both social and nonsocial abstract concepts, social conceptual processing predominates in the right superior ATL. This graded hemispheric specialization is mirrored in the patient results. Our data shed new light on the classic debate about hemispheric differences in semantic and social cognition. These results are considered in the context of models of semantic representation and the emerging data on connectivity for left and right ATL regions. PMID- 26544919 TI - Visual Cortical Representation of Whole Words and Hemifield-split Word Parts. AB - Reading requires the neural integration of visual word form information that is split between our retinal hemifields. We examined multiple visual cortical areas involved in this process by measuring fMRI responses while observers viewed words that changed or repeated in one or both hemifields. We were specifically interested in identifying brain areas that exhibit decreased fMRI responses as a result of repeated versus changing visual word form information in each visual hemifield. Our method yielded highly significant effects of word repetition in a previously reported visual word form area (VWFA) in occipitotemporal cortex, which represents hemifield-split words as whole units. We also identified a more posterior occipital word form area (OWFA), which represents word form information in the right and left hemifields independently and is thus both functionally and anatomically distinct from the VWFA. Both the VWFA and the OWFA were left lateralized in our study and strikingly symmetric in anatomical location relative to known face-selective visual cortical areas in the right hemisphere. Our findings are consistent with the observation that category-selective visual areas come in pairs and support the view that neural mechanisms in left visual cortex- especially those that evolved to support the visual processing of faces--are developmentally malleable and become incorporated into a left-lateralized visual word form network that supports rapid word recognition and reading. PMID- 26544920 TI - Phonological Processing in Primary Progressive Aphasia. AB - Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA. PMID- 26544921 TI - Alternate Ways to Quantify Antibodies. PMID- 26544922 TI - Retrospective analysis on safety and efficacy of everolimus in treatment of metastatic renal cancer patients receiving dialysis. AB - AIMS: This retrospective study aimed to investigate safety and efficacy of everolimus in patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring dialysis. PATIENTS & METHODS: From November 2009 to December 2012, 11 mRCC patients undergoing dialysis were treated with everolimus after failure of anti-VEGF therapy at six Italian institutions. Patient characteristics, safety and outcomes were collected. RESULTS: Progression-free survival and overall survival were determined using the Kaplan-Meier method. Median progression-free survival and overall survival were 9.01 and 15.7 months, respectively. No unexpected adverse events were reported. CONCLUSION: Everolimus appears to be safe in mRCC patients with renal impairment or end-stage renal disease requiring dialysis. Larger prospective studies are required to confirm these findings. PMID- 26544923 TI - LPS-RS attenuation of lipopolysaccharide-induced acute lung injury involves NF kappaB inhibition. AB - In this study, we studied the effect of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), an inhibitor of Toll-like receptor 4 (TLR4), in LPS-induced acute lung injury (ALI). Male Sprague-Dawley rats were treated with LPS-RS (0.1 mg/kg body mass, by intraperitoneal (i.p.) injection) 1 h before LPS injection (10 mg/kg, i.p.). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected 24 h later to determine total and differential cell count, total protein content, levels of lactate dehydrogenase (LDH), histopathological changes, markers of oxidative stress, and mRNA expression of the inhibitory protein nuclear factor kappaB-alpha (NFkappaBIA) and TLR4. Additionally, rings of pulmonary artery were isolated for measuring vascular reactivity. LPS-induced ALI was indicated by increases in total and differential cell count, total protein, and LDH in BALF, and increased lung levels of malondialdehyde (MDA), as well as decreased activity of reduced glutathione (GSH) and superoxide dismutase (SOD). Moreover, LPS increased pulmonary artery contraction in response to phenylephrine (PE). Additionally, LPS downregulated mRNA expression of NFkappaBIA and upregulated mRNA expression of TLR4. LPS caused a marked inflammation in the lung tissue, with tubercular granuloma and numerous neutrophils. Pretreatment with LPS RS protected against LPS-induced ALI by decreasing total and differential cell count, total protein, and LDH in BALF, and increased pulmonary GSH content and SOD activity without affecting MDA content. Additionally, it decreased the elevated PE-induced pulmonary artery contraction. LPS-RS upregulated mRNA expression of NFkappaBIA and downregulated mRNA expression of TLR4. Moreover, LPS RS prevented inflammation in lung tissues. In conclusion, pretreatment with LPS RS protects against LPS-induced ALI in rats through its anti-inflammatory effects, possibly by decreasing the mRNA expression of TLR4 and increasing that of NFkappaBIA. PMID- 26544924 TI - Human Myoblast and Mesenchymal Stem Cell Interactions Visualized by Videomicroscopy. AB - Muscle-derived progenitor cell (myoblast) therapy has promise for the treatment of denervated, weakened, and fibrotic muscle. The best methods for injecting myoblasts to promote fusion and retention have yet to be determined, however. Mesenchymal stem/stromal cells have also been reported to have beneficial effects in restoring damaged tissue, through increasing vascularization and reducing inflammation. The interactions between human primary skeletal myoblasts and bone marrow-derived mesenchymal stem/stromal cells were examined using time-lapse images put into video format. Of interest, there is a high degree of cell-to-cell interaction with microparticles transferring between both cell types, and formation of nanotubules to bridge cytoplasmic contents between the two types of cell. This model provides an in vitro platform for examining mechanisms for cell to-cell interaction preceding myoblast fusion. PMID- 26544925 TI - Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy. AB - BACKGROUND: Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. OBJECTIVES: To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. AUTHORS' CONCLUSIONS: The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results. PMID- 26544927 TI - Cardiomyocyte Cell-Cycle Activity during Preadolescence. PMID- 26544928 TI - Cardiomyocytes Replicate and their Numbers Increase in Young Hearts. PMID- 26544929 TI - Radical Sabbaticals. PMID- 26544930 TI - Peroxisomes Get Loud: A Redox Antidote to Hearing Loss. AB - Pejvakin (PJVK), a protein originally identified in Persian families with sensorineural hearing loss, regulates peroxisomal dynamics and the antioxidant defense triggered by noise exposure in hair cells and auditory neurons of the inner ear. These findings bring peroxisomes to the forefront of noise-induced hearing loss research. PMID- 26544931 TI - Histone Marks Direct Chromosome Segregation. AB - Germline stem cells divide asymmetrically, producing a self-renewing stem cell and a differentiating progenitor. Xie et al. now show that this depends on two asymmetric events that together partition a genome copy, carrying the old histones to the stem cell daughter and a copy with new, unmarked histones to the differentiating daughter. PMID- 26544932 TI - Aire Gets Company for Immune Tolerance. AB - A specialized subset of epithelial cells in the thymus "promiscuously" transcribes thousands of peripheral genes to ensure that developing T cells can test their antigen receptors for dangerous autoreactivity. New findings by Takaba et al. indicate that the transcription factor Fezf2 acts independently of Aire in thymic epithelial cells to generate "genetic noise" for immunological tolerance. PMID- 26544933 TI - Modifications on Translation Initiation. AB - Two studies by Meyer et al. and Wang et al. demonstrate a role for m(6)A modification of mRNA in stimulating translation initiation. These findings add to the growing number of diverse mechanisms for translation initiation in eukaryotes. PMID- 26544934 TI - Design and Analysis of Single-Cell Sequencing Experiments. AB - Recent advances in single-cell sequencing hold great potential for exploring biological systems with unprecedented resolution. Sequencing the genome of individual cells can reveal somatic mutations and allows the investigation of clonal dynamics. Single-cell transcriptome sequencing can elucidate the cell type composition of a sample. However, single-cell sequencing comes with major technical challenges and yields complex data output. In this Primer, we provide an overview of available methods and discuss experimental design and single-cell data analysis. We hope that these guidelines will enable a growing number of researchers to leverage the power of single-cell sequencing. PMID- 26544936 TI - The LC Domain of hnRNPA2 Adopts Similar Conformations in Hydrogel Polymers, Liquid-like Droplets, and Nuclei. AB - Many DNA and RNA regulatory proteins contain polypeptide domains that are unstructured when analyzed in cell lysates. These domains are typified by an over representation of a limited number of amino acids and have been termed prion like, intrinsically disordered or low-complexity (LC) domains. When incubated at high concentration, certain of these LC domains polymerize into labile, amyloid like fibers. Here, we report methods allowing the generation of a molecular footprint of the polymeric state of the LC domain of hnRNPA2. By deploying this footprinting technique to probe the structure of the native hnRNPA2 protein present in isolated nuclei, we offer evidence that its LC domain exists in a similar conformation as that described for recombinant polymers of the protein. These observations favor biologic utility to the polymerization of LC domains in the pathway of information transfer from gene to message to protein. PMID- 26544937 TI - 53BP1 and the LINC Complex Promote Microtubule-Dependent DSB Mobility and DNA Repair. AB - Increased mobility of chromatin surrounding double-strand breaks (DSBs) has been noted in yeast and mammalian cells but the underlying mechanism and its contribution to DSB repair remain unclear. Here, we use a telomere-based system to track DNA damage foci with high resolution in living cells. We find that the greater mobility of damaged chromatin requires 53BP1, SUN1/2 in the linker of the nucleoskeleton, and cytoskeleton (LINC) complex and dynamic microtubules. The data further demonstrate that the excursions promote non-homologous end joining of dysfunctional telomeres and implicated Nesprin-4 and kinesins in telomere fusion. 53BP1/LINC/microtubule-dependent mobility is also evident at irradiation induced DSBs and contributes to the mis-rejoining of drug-induced DSBs in BRCA1 deficient cells showing that DSB mobility can be detrimental in cells with numerous DSBs. In contrast, under physiological conditions where cells have only one or a few lesions, DSB mobility is proposed to prevent errors in DNA repair. PMID- 26544938 TI - Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes. AB - A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. PMID- 26544935 TI - Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. AB - Two decades of studies in multiple model organisms have established the Hippo pathway as a key regulator of organ size and tissue homeostasis. By inhibiting YAP and TAZ transcription co-activators, the Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status. Dysregulation of the Hippo pathway exerts a significant impact on cancer development. Further investigation of the functions and regulatory mechanisms of this pathway will help uncovering the mystery of organ size control and identify new targets for cancer treatment. PMID- 26544939 TI - Vesicle-Mediated Steroid Hormone Secretion in Drosophila melanogaster. AB - Steroid hormones are a large family of cholesterol derivatives regulating development and physiology in both the animal and plant kingdoms, but little is known concerning mechanisms of their secretion from steroidogenic tissues. Here, we present evidence that in Drosophila, endocrine release of the steroid hormone ecdysone is mediated through a regulated vesicular trafficking mechanism. Inhibition of calcium signaling in the steroidogenic prothoracic gland results in the accumulation of unreleased ecdysone, and the knockdown of calcium-mediated vesicle exocytosis components in the gland caused developmental defects due to deficiency of ecdysone. Accumulation of synaptotagmin-labeled vesicles in the gland is observed when calcium signaling is disrupted, and these vesicles contain an ABC transporter that functions as an ecdysone pump to fill vesicles. We propose that trafficking of steroid hormones out of endocrine cells is not always through a simple diffusion mechanism as presently thought, but instead can involve a regulated vesicle-mediated release process. PMID- 26544940 TI - Stable Chromosome Condensation Revealed by Chromosome Conformation Capture. AB - Chemical cross-linking and DNA sequencing have revealed regions of intra chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. PMID- 26544941 TI - Estrogen Receptor beta Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. AB - Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) beta levels, enhanced ERbeta activity was detected in endometriotic tissues, and the inhibition of enhanced ERbeta activity by an ERbeta-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERbeta function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERbeta interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-alpha-induced apoptosis. ERbeta also interacts with components of the cytoplasmic inflammasome to increase interleukin 1beta and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERbeta function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERbeta function. PMID- 26544942 TI - Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance. AB - Self-tolerance to immune reactions is established via promiscuous expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), leading to the elimination of T cells that respond to self-antigens. The transcriptional regulator Aire has been thought to be sufficient for the induction of TRAs, despite some indications that other factors may promote TRA expression in the thymus. Here, we show that the transcription factor Fezf2 directly regulates various TRA genes in mTECs independently of Aire. Mice lacking Fezf2 in mTECs displayed severe autoimmune symptoms, including the production of autoantibodies and inflammatory cell infiltration targeted to peripheral organs. These responses differed from those detected in Aire-deficient mice. Furthermore, Fezf2 expression and Aire expression are regulated by distinct signaling pathways and promote the expression of different classes of proteins. Thus, two independent factors, Fezf2 and Aire, permit the expression of TRAs in the thymus to ensure immune tolerance. PMID- 26544943 TI - Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology. AB - While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive. PMID- 26544945 TI - No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice. AB - The magnitude of cardiomyocyte generation in the adult heart has been heavily debated. A recent report suggests that during mouse preadolescence, cardiomyocyte proliferation leads to a 40% increase in the number of cardiomyocytes. Such an expansion would change our understanding of heart growth and have far-reaching implications for cardiac regeneration. Here, using design-based stereology, we found that cardiomyocyte proliferation accounted for 30% of postnatal DNA synthesis; however, we were unable to detect any changes in cardiomyocyte number after postnatal day 11. (15)N-thymidine and BrdU analyses provided no evidence for a proliferative peak in preadolescent mice. By contrast, cardiomyocyte multinucleation comprises 57% of postnatal DNA synthesis, followed by cardiomyocyte nuclear polyploidisation, contributing with 13% to DNA synthesis within the second and third postnatal weeks. We conclude that the majority of cardiomyocytes is set within the first postnatal week and that this event is followed by two waves of non-replicative DNA synthesis. This Matters Arising paper is in response to Naqvi et al. (2014), published in Cell. See also the associated Correspondence by Soonpaa et al. (2015), and the response by Naqvi et al. (2015), published in this issue. PMID- 26544946 TI - SnapShot: T Cell Exhaustion. PMID- 26544947 TI - Application of chromatography technology in the separation of active alkaloids from Hypecoum leptocarpum and their inhibitory effect on fatty acid synthase. AB - A method that involved the combination of pH-zone-refining counter-current chromatography and semipreparative reversed-phase liquid chromatography has been established for the preparative separation of alkaloids from Hypecoum leptocarpum. From 1.2 g of crude sample, 31 mg N-feruloyltyramine, 27 mg oxohydrastinine, 47 mg hydroprotopine, 25 mg leptopidine, and 18 mg hypecocarpine have been obtained. The structure of the new compound, hypecocarpine, is confirmed based on the analysis of spectroscopic data, including NMR, UV, and IR spectroscopy and positive electrospray ionization mass spectrometry. The known chemical structures were characterized on the basis of (1) H and (13) C NMR spectroscopy. The purities of the five alkaloids are all over 92.7% as determined by high-performance liquid chromatography. The alkaloids' cytotoxicity in breast cancer cells is assessed by using a Cell Counting Kit assay and their inhibitory effect on fatty acid synthase expression is assessed by a Western blot assay. These results suggest that leptopidine could suppress growth and induce cytotoxicity in breast cancer cells and that the cytotoxicity of leptopidine may be related to its inhibitory effect on fatty acid synthase expression. PMID- 26544948 TI - Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome. AB - Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions. PMID- 26544949 TI - Ernst Rudin's Unpublished 1922-1925 Study "Inheritance of Manic-Depressive Insanity": Genetic Research Findings Subordinated to Eugenic Ideology. AB - In the early 20th century, there were few therapeutic options for mental illness and asylum numbers were rising. This pessimistic outlook favoured the rise of the eugenics movement. Heredity was assumed to be the principal cause of mental illness. Politicians, scientists and clinicians in North America and Europe called for compulsory sterilisation of the mentally ill. Psychiatric genetic research aimed to prove a Mendelian mode of inheritance as a scientific justification for these measures. Ernst Rudin's seminal 1916 epidemiological study on inheritance of dementia praecox featured large, systematically ascertained samples and statistical analyses. Rudin's 1922-1925 study on the inheritance of "manic-depressive insanity" was completed in manuscript form, but never published. It failed to prove a pattern of Mendelian inheritance, counter to the tenets of eugenics of which Rudin was a prominent proponent. It appears he withheld the study from publication, unable to reconcile this contradiction, thus subordinating his carefully derived scientific findings to his ideological preoccupations. Instead, Rudin continued to promote prevention of assumed hereditary mental illnesses by prohibition of marriage or sterilisation and was influential in the introduction by the National Socialist regime of the 1933 "Law for the Prevention of Hereditarily Diseased Offspring" (Gesetz zur Verhutung erbkranken Nachwuchses). PMID- 26544950 TI - Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium. AB - BACKGROUND: Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS). METHODOLOGY/PRINCIPAL FINDINGS: We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota communities after infection. Whilst treatment with CMS appeared to have little impact on microbial community composition after infection, or the change undergone by communities in reaching that state, when Gram negative organisms (excluding Pseudomonadales) were considered together as a group there was a significant decrease in their relative proportion that was only observed in the sheep treated with CMS. With only one exception the reduction was seen in both direct and remote lung segments. This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment. CONCLUSIONS/SIGNIFICANCE: The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection. PMID- 26544951 TI - Laparoscopic fundoplication surgery versus medical management for gastro oesophageal reflux disease (GORD) in adults. AB - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common condition with 3% to 33% of people from different parts of the world suffering from GORD. There is considerable uncertainty about whether people with GORD should receive an operation or medical treatment for controlling the condition. OBJECTIVES: To assess the benefits and harms of laparoscopic fundoplication versus medical treatment for people with gastro-oesophageal reflux disease. SEARCH METHODS: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group (UGPD) Trials Register (June 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 6, 2015), Ovid MEDLINE (1966 to June 2015), and EMBASE (1980 to June 2015) to identify randomised controlled trials. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCT) comparing laparoscopic fundoplication with medical treatment in people with GORD irrespective of language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or standardised mean difference (SMD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available case analysis. MAIN RESULTS: Four studies met the inclusion criteria for the review, and provided information on one or more outcomes for the review. A total of 1160 participants in the four RCTs were either randomly assigned to laparoscopic fundoplication (589 participants) or medical treatment with proton pump inhibitors (571 participants). All the trials included participants who had had reflux symptoms for at least six months and had received long-term acid suppressive therapy. All the trials included only participants who could undergo surgery if randomised to the surgery arm. All of the trials were at high risk of bias. The overall quality of evidence was low or very low. None of the trials reported long-term health-related quality of life (HRQoL) or GORD-specific quality of life (QoL).The difference between laparoscopic fundoplication and medical treatment was imprecise for overall short-term HRQOL (SMD 0.14, 95% CI 0.02 to 0.30; participants = 605; studies = 3), medium-term HRQOL (SMD 0.03, 95% CI -0.19 to 0.24; participants = 323; studies = 2), medium-term GORD-specific QoL (SMD 0.28, 95% CI -0.27 to 0.84; participants = 994; studies = 3), proportion of people with adverse events (surgery: 7/43 (adjusted proportion = 14.0%); medical: 0/40 (0.0%); RR 13.98, 95% CI 0.82 to 237.07; participants = 83; studies = 1), long-term dysphagia (surgery: 27/118 (adjusted proportion = 22.9%); medical: 28/110 (25.5%); RR 0.90, 95% CI 0.57 to 1.42; participants = 228; studies = 1), and long-term reflux symptoms (surgery: 29/118 (adjusted proportion = 24.6%); medical: 41/115 (35.7%); RR 0.69, 95% CI 0.46 to 1.03; participants = 233; studies = 1).The short-term GORD-specific QoL was better in the laparoscopic fundoplication group than in the medical treatment group (SMD 0.58, 95% CI 0.46 to 0.70; participants = 1160; studies = 4).The proportion of people with serious adverse events (surgery: 60/331 (adjusted proportion = 18.1%); medical: 38/306 (12.4%); RR 1.46, 95% CI 1.01 to 2.11; participants = 637; studies = 2), short term dysphagia (surgery: 44/331 (adjusted proportion = 12.9%); medical: 11/306 (3.6%); RR 3.58, 95% CI 1.91 to 6.71; participants = 637; studies = 2), and medium-term dysphagia (surgery: 29/288 (adjusted proportion = 10.2%); medical: 5/266 (1.9%); RR 5.36, 95% CI 2.1 to 13.64; participants = 554; studies = 1) was higher in the laparoscopic fundoplication group than in the medical treatment group.The proportion of people with heartburn at short term (surgery: 29/288 (adjusted proportion = 10.0%); medical: 59/266 (22.2%); RR 0.45, 95% CI 0.30 to 0.69; participants = 554; studies = 1), medium term (surgery: 12/288 (adjusted proportion = 4.2%); medical: 59/266 (22.2%); RR 0.19, 95% CI 0.10 to 0.34; participants = 554; studies = 1), long term (surgery: 46/111 (adjusted proportion = 41.2%); medical: 78/106 (73.6%); RR 0.56, 95% CI 0.44 to 0.72); participants = 217; studies = 1) and those with reflux symptoms at short-term (surgery: 6/288 (adjusted proportion = 2.0%); medical: 53/266 (19.9%); RR 0.10, 95% CI 0.05 to 0.24; participants = 554; studies = 1) and medium term (surgery: 6/288 (adjusted proportion = 2.1%); medical: 37/266 (13.9%); RR 0.15, 95% CI 0.06 to 0.35; participants = 554; studies = 1) was less in the laparoscopic fundoplication group than in the medical treatment group. AUTHORS' CONCLUSIONS: There is considerable uncertainty in the balance of benefits versus harms of laparoscopic fundoplication compared to long-term medical treatment with proton pump inhibitors. Further RCTs of laparoscopic fundoplication versus medical management in patients with GORD should be conducted with outcome-assessor blinding and should include all participants in the analysis. Such trials should include long term patient-orientated outcomes such as treatment-related adverse events (including severity), quality of life, and also report on the social and economic impact of the adverse events and symptoms. PMID- 26544952 TI - Lack of Acute Hand Care in the Southwest United States. AB - OBJECTIVES: To describe the epidemiology of acute hand injuries and hand infections and to describe the factors associated with the transfer of these patients to a level 1 trauma center. In addition, we sought to understand management before transfer. DESIGN: Retrospective review of patients with hand trauma or hand infection transferred to our level 1 trauma center from May 2009 to August 2011. We also identified hospitals with emergency departments (EDs) in our region and surveyed ED providers in these hospitals with regard to acute hand care. SETTING: A level 1 trauma center in the United States. PATIENTS: Four hundred sixty consecutive transfers for acute hand care. RESULTS: The average patient age was 38. Most were male (84%), uninsured (51%), and from another county (59%). The average distance of transfer was 51 miles, and 80% were transferred by ground ambulance. The most common reasons for transfer were amputations (24%), infections (21%), lacerations (17%), and fractures/dislocations (16%). Of the 345 hospitals with an ED surveyed, 71% never had hand surgery coverage. CONCLUSIONS: Patients transferred for acute hand care were young and male, and traveled an average 51 miles to get to our center. More than half of these patients were treated and discharged from our ED. This indicates that a majority may have been managed in a clinic setting. Most EDs in our region do not have a hand surgeon available. Most emergency physicians surveyed had received little training in management of acute hand injuries and hand infections. Further research is needed to identify methods to remove barriers to provision of care for patients with hand trauma. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26544953 TI - Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects. AB - OBJECTIVES: To determine factors associated with developing nonunion or delayed healing after open fracture. DESIGN: Prospective cohort between 2001 and 2009. SETTING: Three level 1 Canadian trauma centers. PARTICIPANTS: Seven hundred thirty-six (791 fractures) subjects were enrolled. Six hundred eighty-nine (94%) subjects (739 fractures) provided adequate outcome data. INTERVENTION: Subjects were followed until fracture(s) healed; phone interviews and chart reviews were conducted 1 year after fracture. Patient, fracture, and injury information, and time to surgery and antibiotics were recorded during hospitalization. MAIN OUTCOME MEASUREMENTS: Nonunion defined as unplanned surgical intervention after definitive wound closure or incomplete radiographic healing at 1 year and delayed healing defined as 2 consecutive clinical assessments showing no radiographic progression or incomplete radiographic healing between 6 months and 1 year. RESULTS: There were 413 (52%) tibia/fibular, 285 (36%) upper extremity, and 93 (13%) femoral fractures. Nonunion developed in 124 (17%) and delayed healing in 63 (8%) fractures. The median time to surgery was not different for fractures that developed nonunion compared with those who did not (P = 0.36). Deep infection [Odd ratio (OR) 12.75; 95% confidence interval (CI) 6.07-26.8], grade 3A fractures (OR 2.49; 95% CI, 1.30-4.78), and smoking (OR 1.73; 95% CI, 1.09 2.76) were significantly associated with developing a nonunion. Delayed healing was also significantly associated with deep infection (OR 4.34; 95% CI, 1.22 15.48) and grade 3B/C fractures (OR 3.69; 95% CI, 1.44-9.44). Multivariate regression found no association between nonunion and time to surgery (P = 0.15) or antibiotics (P = 0.70). CONCLUSIONS: Deep infection and higher Gustilo grade fractures were associated with nonunion and delayed healing. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 26544944 TI - The Molecular Taxonomy of Primary Prostate Cancer. AB - There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects. PMID- 26544954 TI - Augmentation of Fracture Healing Using Soft Callus. AB - OBJECTIVES: This study sought to investigate the effect of soft callus removal and reapplication in a rat closed femur fracture model. We hypothesized that removing soft callus will impair fracture healing, whereas reapplication will facilitate healing. METHODS: A closed midshaft femur fracture was created in 78 rats and stabilized with an intramedullary wire. Seven days later, rats were equally divided and fractures surgically exposed. In the control group, no callus was removed, whereas in the callus removal group CR(-) group, the callus was removed and in the callus replaced group CR(+), callus was removed and replaced. Half of the rats were killed at 4 and 7 weeks. Fracture healing was graded with radiographs and callus volume measured with micro-CT. Mechanical torsion properties were measured, and histologic analysis was conducted. RESULTS: At both end points, evidence of delayed healing was found on radiographs and micro-CT in CR(-) rats (P = 0.0001), whereas CR(+) rats showed normal fracture healing compared with controls. The normalized callus volume was similar in all groups at both end points. At 7 weeks, the maximum stiffness in CR(-) rats was 68% less than control (P = 0.0001). Stiffness increased 55% in CR(+) rats from CR(-) rats (P = 0.0017). Histology supported our findings with complete endochondral ossification in CR(+) rats but wide areas of hyaline cartilage in CR(-) rats at 7 weeks. CONCLUSIONS: Removal of soft callus in a rat model delays fracture healing at early and late time points, whereas replacement mitigates these negative consequences. Replacing the soft callus should be considered in all osteosynthesis procedures. PMID- 26544957 TI - Intraoperative Mapping and Monitoring for Rootlets of the Lower Cranial Nerves Related to Vocal Cord Movement. AB - BACKGROUND: Damage to the motor division of the lower cranial nerves that run into the jugular foramen leads to hoarseness, dysphagia, and the risk of aspiration pneumonia; therefore, its functional preservation during surgical procedures is important. Intraoperative mapping and monitoring of the motor rootlets at the cerebellomedullary cistern using endotracheal tube electrodes is a safe and effective procedure to prevent its injury. OBJECTIVE: To study the location of the somatic and autonomic motor fibers of the lower cranial nerves related to vocal cord movement. METHODS: Twenty-four patients with pathologies at the cerebellopontine lesion were studied. General anesthesia was maintained with fentanyl and propofol. A monopolar stimulator was used at amplitudes of 0.05 to 0.1 mA. Both acoustic and visual signals were displayed as vocalis muscle electromyographic activity using endotracheal tube surface electrodes. RESULTS: The average number of rootlets was 7.4 (range, 5-10); 75% of patients had 7 or 8 rootlets. As many as 6 rootlets (2-4 in most cases) were responsive in each patient. In 23 of the 24 patients, the responding rootlets congregated on the caudal side. The maximum electromyographic response was predominantly in the most caudal or second most caudal rootlet in 79%. CONCLUSION: The majority of motor fibers of the lower cranial nerves run through the caudal part of the rootlets at the cerebellomedullary cistern, and the maximal electromyographic response was elicited at the most caudal or second most caudal rootlet. ABBREVIATION: EMG, electromyographic. PMID- 26544955 TI - The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline. AB - BACKGROUND: Substantial progress in high-throughput metagenomic sequencing methodologies has enabled the characterisation of bacteria from various origins (for example gut and skin). However, the recently-discovered bacterial microbiota present within animal internal tissues has remained unexplored due to technical difficulties associated with these challenging samples. RESULTS: We have optimized a specific 16S rDNA-targeted metagenomics sequencing (16S metabarcoding) pipeline based on the Illumina MiSeq technology for the analysis of bacterial DNA in human and animal tissues. This was successfully achieved in various mouse tissues despite the high abundance of eukaryotic DNA and PCR inhibitors in these samples. We extensively tested this pipeline on mock communities, negative controls, positive controls and tissues and demonstrated the presence of novel tissue specific bacterial DNA profiles in a variety of organs (including brain, muscle, adipose tissue, liver and heart). CONCLUSION: The high throughput and excellent reproducibility of the method ensured exhaustive and precise coverage of the 16S rDNA bacterial variants present in mouse tissues. This optimized 16S metagenomic sequencing pipeline will allow the scientific community to catalogue the bacterial DNA profiles of different tissues and will provide a database to analyse host/bacterial interactions in relation to homeostasis and disease. PMID- 26544958 TI - Expectant Mothers Maximizing Opportunities: Maternal Characteristics Moderate Multifactorial Prenatal Stress in the Prediction of Birth Weight in a Sample of Children Adopted at Birth. AB - BACKGROUND: Mothers' stress in pregnancy is considered an environmental risk factor in child development. Multiple stressors may combine to increase risk, and maternal personal characteristics may offset the effects of stress. This study aimed to test the effect of 1) multifactorial prenatal stress, integrating objective "stressors" and subjective "distress" and 2) the moderating effects of maternal characteristics (perceived social support, self-esteem and specific personality traits) on infant birthweight. METHOD: Hierarchical regression modeling was used to examine cross-sectional data on 403 birth mothers and their newborns from an adoption study. RESULTS: Distress during pregnancy showed a statistically significant association with birthweight (R2 = 0.032, F(2, 398) = 6.782, p = .001). The hierarchical regression model revealed an almost two-fold increase in variance of birthweight predicted by stressors as compared with distress measures (R2Delta = 0.049, F(4, 394) = 5.339, p < .001). Further, maternal characteristics moderated this association (R2Delta = 0.031, F(4, 389) = 3.413, p = .009). Specifically, the expected benefit to birthweight as a function of higher SES was observed only for mothers with lower levels of harm-avoidance and higher levels of perceived social support. Importantly, the results were not better explained by prematurity, pregnancy complications, exposure to drugs, alcohol or environmental toxins. CONCLUSIONS: The findings support multidimensional theoretical models of prenatal stress. Although both objective stressors and subjectively measured distress predict birthweight, they should be considered distinct and cumulative components of stress. This study further highlights that jointly considering risk factors and protective factors in pregnancy improves the ability to predict birthweight. PMID- 26544959 TI - Impact of Bacterial Vaginosis on Perineal Tears during Delivery: A Prospective Cohort Study. AB - OBJECTIVE: Long term effects of perineal tears pose a major worldwide health issue for women during delivery. Since bacterial vaginosis is related to major obstacles in obstetrics the aim of this study was to determine the relationship between bacterial vaginosis and the occurrence of perineal tears during vaginal delivery. METHODS: Between June 2013 and December 2013 pregnant women delivering after 37 weeks were recruited at one University hospital / tertiary care referral center in the course of this single-center, prospective cohort study. Bacterial vaginosis was assessed according to Nugent score method. Logistic-regression model was used to estimate odds ratios, adjusted for other risk factors to test the relationship between bacterial vaginosis and the occurrence of 1st to 4th degree perineal tears in women undergoing vaginal delivery. RESULTS: A total of 728 woman were included, 662 analyzed with a complete Nugent Score of the vaginal swab. The prevalence of 1st to 4th degree perineal tears was 35.8% (95% Confidence Interval (95%CI) = [32.2; 39.6]). The presence of BV was not significantly associated to the incidence of perineal tears neither in the univariate analysis (crude Odds Ratio = 1.43; 95%CI = [0.79; 2.60]; p = 0.235) nor in the multivariate analysis (adjusted Odds Ratio = 1.65; 95%CI = [0.81; 3.36]; p = 0.167). Instrumental delivery was the most important risk factor for perineal lacerations. CONCLUSIONS: There is no evidence that vaginosis is a risk factor for vaginal tears. TRIAL REGISTRATION: ClinicalTrials.gov N degrees NCT01822782. PMID- 26544960 TI - Lysine Methylation of the Valosin-Containing Protein (VCP) Is Dispensable for Development and Survival of Mice. AB - Valosin-containing protein (VCP) is a homohexameric ATPase involved in a multitude cellular processes and it was recently shown that VCP is trimethylated at lysine 315 by the VCP lysine methyltransferase (VCPKMT). Here, we generated and validated a constitutive knockout mouse by targeting exon 1-4 of the Vcpkmt gene. We show that Vcpkmt is ubiquitously expressed in all tissues examined and confirm the sub-cellular localization to the cytoplasm. We show by (I) mass spectrometric analysis, (II) VCPKMT-mediated in vitro methylation of VCP in cell extracts and (III) immunostaining with a methylation specific antibody, that in Vcpkmt-/- mice the methylation of lysine 315 in VCP is completely abolished. In contrast, VCP is almost exclusively trimethylated in wild-type mice. Furthermore, we investigated the specificity of VCPKMT with in vitro methylation assays using as source of substrate protein extracts from Vcpkmt-/- mouse organs or three human Vcpkmt-/- cell lines. The results show that VCPKMT is a highly specific enzyme, and suggest that VCP is its sole substrate. The Vcpkmt-/- mice were viable, fertile and had no obvious pathological phenotype. Their body weight, life span and acute endurance capacity were comparable to wild-type controls. Overall the results show that VCPKMT is an enzyme required for methylation of K315 of VCP in vivo, but VCPKMT is not essential for development or survival under unstressed conditions. PMID- 26544961 TI - Evaluation of Reliability and Validity of the Hendrich II Fall Risk Model in a Chinese Hospital Population. AB - To translate, validate and examine the reliability and validity of a Chinese version of the Hendrich II Fall risk Model (HFRM) in predicting falls in elderly inpatient. A sample of 989 Chinese elderly inpatients was recruited upon admission at the Peking Union Medical College Hospital. The inpatients were assessed for fall risk using the Chinese version of the HFRM at admission. The reliability of the Chinese version of the HFRM was determined using the internal consistency and test-rested methods. Validity was determined using construct validity and convergent validity. Receiver operating characteristic (ROC) curves were created to determine the sensitivity and specificity. The Chinese version of the HFRM showed excellent repeatability with an intra-class correlation coefficient (ICC) of 0.9950 (95% confidence interval (CI): 0.9923-0.9984). The inter-rater reliability was high with an ICC of 0.9950 (95%CI: 0.9923-0.9984). Cronbach's alpha coefficient was 0.366. Content validity was excellent, with a content validity ratio of 0.9333. The Chinese version of the HFRM had a sensitivity of 72% and a specificity of 69% when using a cut-off of 5 points on the scale. The area under the curve (AUC) was 0.815 (P<0.001). The Chinese version of the HFRM showed good reliability and validity in assessing the risk of fall in Chinese elderly inpatients. PMID- 26544962 TI - Most Undirected Random Graphs Are Amplifiers of Selection for Birth-Death Dynamics, but Suppressors of Selection for Death-Birth Dynamics. AB - We analyze evolutionary dynamics on graphs, where the nodes represent individuals of a population. The links of a node describe which other individuals can be displaced by the offspring of the individual on that node. Amplifiers of selection are graphs for which the fixation probability is increased for advantageous mutants and decreased for disadvantageous mutants. A few examples of such amplifiers have been developed, but so far it is unclear how many such structures exist and how to construct them. Here, we show that almost any undirected random graph is an amplifier of selection for Birth-death updating, where an individual is selected to reproduce with probability proportional to its fitness and one of its neighbors is replaced by that offspring at random. If we instead focus on death-Birth updating, in which a random individual is removed and its neighbors compete for the empty spot, then the same ensemble of graphs consists of almost only suppressors of selection for which the fixation probability is decreased for advantageous mutants and increased for disadvantageous mutants. Thus, the impact of population structure on evolutionary dynamics is a subtle issue that will depend on seemingly minor details of the underlying evolutionary process. PMID- 26544963 TI - Population Structure of Montastraea cavernosa on Shallow versus Mesophotic Reefs in Bermuda. AB - Mesophotic coral reef ecosystems remain largely unexplored with only limited information available on taxonomic composition, abundance and distribution. Yet, mesophotic reefs may serve as potential refugia for shallow-water species and thus understanding biodiversity, ecology and connectivity of deep reef communities is integral for resource management and conservation. The Caribbean coral, Montastraea cavernosa, is considered a depth generalist and is commonly found at mesophotic depths. We surveyed abundance and size-frequency of M. cavernosa populations at six shallow (10m) and six upper mesophotic (45m) sites in Bermuda and found population structure was depth dependent. The mean surface area of colonies at mesophotic sites was significantly smaller than at shallow sites, suggesting that growth rates and maximum colony surface area are limited on mesophotic reefs. Colony density was significantly higher at mesophotic sites, however, resulting in equal contributions to overall percent cover. Size frequency distributions between shallow and mesophotic sites were also significantly different with populations at mesophotic reefs skewed towards smaller individuals. Overall, the results of this study provide valuable baseline data on population structure, which indicate that the mesophotic reefs of Bermuda support an established population of M. cavernosa. PMID- 26544964 TI - Behavioral effects of beta-phenylethylamine and various monomethylated and monohalogenated analogs in mice are mediated by catecholaminergic mechanisms. AB - The effects of the administration [intraperitoneally, 15 and 75 mg/kg, except alpha-MePEA (amphetamine, AMPH) at 5 and 10 mg/kg] of beta-phenylethylamine (PEA), its methylated (o-Me-, p-Me-, alpha-Me-, beta-Me-, N-Me-, p-OMe-, N,N-di Me-, and 3,4-diOH-N-Me-), para-halogenated (Br-, Cl-, F-, and I-), and other derivatives for example, p-OHPEA (p-tyramine), on Swiss male albino mice caged behavior fall into 3 broad categories. (1) N,N-diMe-, 3,4-diOH-N-Me-, and o-MePEA tend to reduce the behavioral activity, (2) p-OH and p-IPEA were without noticeable effects, and (3) the remaining compounds increased locomotor activity, produced hyperexcitability and fighting, jumping and vocalization, and convulsion in a graded manner (listed in increasing order p-OMe-, beta-Me-, p-Cl-, p-Br-, p F-, p-Me-, and N-MePEA, PEA itself and alpha-MePEA). The latter compound (amphetamine) being the most potent among them; equieffective but with lower potency were p-MePEA, N-MePEA, and PEA itself. The effects of PEAs upon group cage behavior were increased by pretreatment with pargyline (1.5 hours; 15 mg/kg) and decreased after reserpine or haloperidol [4 hours and/or 24 hours (2.5 and/or 2.5 mg/kg) and 1 hour (1 mg/kg), respectively], reaching full suppression with the double-dose regimen of reserpine and single dose of haloperidol. As expected, none of these substances by themselves were noticeable changed group mice activity or stereotypic behavior. The effects of test amines and catecholamine modulating agents on stereotypy were assessed by rating the sequentially occurring behaviors: increased exploratory behavior with increased sniffing; occasional side-to-side head weaving; paw-licking and other grooming; gnawing, fighting and continuous side-to-side head weaving, and periodic episodes of "popcorn" behavior, during which all mice in the cage ran, jumped, and vocalized. In general, rank efficacy in eliciting stereotype aligned with rank efficacy in affecting group cage behavior. Our results show that a number of as yet little studied monomethylated and monohalogenated PEA analogs share a similar behavioral profile with PEA and AMPH. Behavioral changes observed appear to be, at least in part, mediated by catecholaminergic mechanism as they are modulated by drugs known to influence catecholamine activity. PEA analogs provide a large number of clinically useful drugs; whether further studies on these novel amines will lead to the rational design of newer, safer, and effective PEA-class drugs remains to be seen. PMID- 26544965 TI - Universal Host Materials for High-Efficiency Phosphorescent and Delayed Fluorescence OLEDs. AB - A series of bipolar hosts, namely, 5-(2-(9H-carbazol-9-yl)-phenyl)-1,3 dipyrazolbenzene (o-CzDPz), 5-(3-(9H-carbazol-9-yl)-phenyl)-1,3-dipyrazolbenzene (m-CzDPz), 5-(9-phenyl-9H-carbazol-3-yl)-1,3-dipyrazolbenzene (3-CzDPz), and 5 (3,5-di(9H-carbazol-9-yl)-phenyl)-1,3-dipyrazolbenzene (mCPDPz), are developed for phosphorescent and thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs). They are designed by selecting pyrazole as n-type unit and carbazole as p-type one. The triplet energy (E(T)), the frontier molecular orbital level, and charge transporting abilities, are adjusted by varying the molar ratio of pyrazole to carbazole and the linking mode between them. They have high E(T) values of 2.76-3.02 eV. Their electroluminescence performance is evaluated by fabricating both phosphorescent and TADF devices with blue or green emitters. The m-CzDPz hosted blue phosphorescent OLEDs achieves high efficiency of 48.3 cd A(-1) (26.8%), the 3-CzDPz hosted green phosphorescent device exhibits 91.2 cd A(-1) (29.0%). The blue and green TADF devices with 3 CzDPz host also reach high efficiencies of 26.2 cd A(-1) (15.8%) and 41.1 cd A( 1) (13.3%), respectively. The excellent performance of all these OLEDs verifies that these pyrazole-based bipolar compounds are capable of being universal host materials for OLED application. The influence of molar ratio of n-type unit to p type one and the molecular conformation of these hosts on their device performance is discussed and interpreted. PMID- 26544966 TI - Perspectives on Temperature Management. PMID- 26544968 TI - The Neutrophil-Platelet Score (NPS) Predicts Survival in Primary Operable Colorectal Cancer and a Variety of Common Cancers. AB - INTRODUCTION: Recent in-vitro studies have suggested that a critical checkpoint early in the inflammatory process involves the interaction between neutrophils and platelets. This confirms the importance of the innate immune system in the elaboration of the systemic inflammatory response. The aim of the present study was to examine whether a combination of the neutrophil and platelet counts were predictive of survival in patients with cancer. METHODS: Patients with histologically proven colorectal cancer who underwent potentially curative resection at a single centre between March 1999 and May 2013 (n = 796) and patients with cancer from the Glasgow Inflammation Outcome Study, who had a blood sample taken between January 2000 and December 2007 (n = 9649) were included in the analysis. RESULTS: In the colorectal cancer cohort, there were 173 cancer and 135 non-cancer deaths. In patients undergoing elective surgery, cancer-specific survival (CSS) at 5 years ranged from 97% in patients with TNM I disease and NPS = 0 to 57% in patients with TNM III disease and NPS = 2 (p = 0.019) and in patients undergoing elective surgery for node-negative colon cancer from 98% (TNM I, NPS = 0) to 65% (TNM II, NPS = 2) (p = 0.004). In those with a variety of common cancers there were 5218 cancer and 929 non-cancer deaths. On multivariate analysis, adjusting for age and sex and stratified by tumour site, incremental increase in the NPS was significantly associated with poorer CSS (p<0.001). CONCLUSION: The neutrophil-platelet score predicted survival in a variety of common cancers and highlights the importance of the innate immune system in patients with cancer. PMID- 26544967 TI - Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress. AB - BACKGROUND: Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. OBJECTIVES: To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children's memory and learning. METHODS: Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable adjusted linear regression including effect modification by stress and sex. RESULTS: Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had <=12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P3-way interaction = 0.04). CONCLUSION: The associations between prenatal exposure to black carbon and stress with children's memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups. PMID- 26544969 TI - Vibration-reorientation dynamics, structural changes and its interrelation with the phase transition in polycrystalline [Cr(OC(NH2)2)6](BF4)3. AB - Polycrystalline hexakis(urea-O)chromium(III) tetrafluoroborate possesses in the temperature range of 295-105 K one solid-solid phase transition at T(C) ~ 255 K. Analysis of the band shapes associated with the nu(as)(CN) and delta(as)(NH2) vibrational modes of the Fourier transform infrared absorption (FT-IR) spectra, registered in the temperature range of 295-10 K, indicated existence of fast (tau(R) ~ 10(-12) s) reorientational motion of the protons from NH2 groups belonging to OC(NH2)2 (urea) ligands, which does not suddenly change at T(C). Moreover, splitting of the IR bands associated with the nu(as)(NH), nu(s)(NH) and nu(as)(BF)F2/nu(s)(CN) modes at T(C) indicated that this phase transition is associated with a change of crystal structure. Similar analysis of the Raman scattering bands (FT-RS), associated with the delta(s)(FBF)E, nu(s)(BF)A and nu(as)(BF)F2/nu(s)(CN) vibrational modes, indicated fast reorientation of the BF4(-) ions, which does not suddenly change at T(C), and additionally confirmed structural character of this phase transition. Results obtained from vibrational spectroscopy measurements are compatible with that obtained by electron paramagnetic resonance spectroscopy (EPR) measurements in function of temperature, where rapid narrowing of the EPR line in the vicinity of the T(C) was observed. PMID- 26544971 TI - Correction: Defining the Roles of IFN-gamma and IL-17A in Inflammation and Protection against Helicobacter pylori Infection. PMID- 26544970 TI - Plasmid DNA Vaccine Co-Immunisation Modulates Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice. AB - BACKGROUND: An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM) delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN) and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice. RESULTS: Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNgamma responses were preserved in co immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity. SIGNIFICANCE: These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines. PMID- 26544972 TI - QTL Mapping of Sex Determination Loci Supports an Ancient Pathway in Ants and Honey Bees. AB - Sex determination mechanisms play a central role in life-history characteristics, affecting mating systems, sex ratios, inbreeding tolerance, etc. Downstream components of sex determination pathways are highly conserved, but upstream components evolve rapidly. Evolutionary dynamics of sex determination remain poorly understood, particularly because mechanisms appear so diverse. Here we investigate the origins and evolution of complementary sex determination (CSD) in ants and bees. The honey bee has a well-characterized CSD locus, containing tandemly arranged homologs of the transformer gene [complementary sex determiner (csd) and feminizer (fem)]. Such tandem paralogs appear frequently in aculeate hymenopteran genomes. However, only comparative genomic, but not functional, data support a broader role for csd/fem in sex determination, and whether species other than the honey bee use this pathway remains controversial. Here we used a backcross to test whether csd/fem acts as a CSD locus in an ant (Vollenhovia emeryi). After sequencing and assembling the genome, we computed a linkage map, and conducted a quantitative trait locus (QTL) analysis of diploid male production using 68 diploid males and 171 workers. We found two QTLs on separate linkage groups (CsdQTL1 and CsdQTL2) that jointly explained 98.0% of the phenotypic variance. CsdQTL1 included two tandem transformer homologs. These data support the prediction that the same CSD mechanism has indeed been conserved for over 100 million years. CsdQTL2 had no similarity to CsdQTL1 and included a 236 kb region with no obvious CSD gene candidates, making it impossible to conclusively characterize it using our data. The sequence of this locus was conserved in at least one other ant genome that diverged >75 million years ago. By applying QTL analysis to ants for the first time, we support the hypothesis that elements of hymenopteran CSD are ancient, but also show that more remains to be learned about the diversity of CSD mechanisms. PMID- 26544974 TI - A New Extension of the Binomial Error Model for Responses to Items of Varying Difficulty in Educational Testing and Attitude Surveys. AB - We put forward a new item response model which is an extension of the binomial error model first introduced by Keats and Lord. Like the binomial error model, the basic latent variable can be interpreted as a probability of responding in a certain way to an arbitrarily specified item. For a set of dichotomous items, this model gives predictions that are similar to other single parameter IRT models (such as the Rasch model) but has certain advantages in more complex cases. The first is that in specifying a flexible two-parameter Beta distribution for the latent variable, it is easy to formulate models for randomized experiments in which there is no reason to believe that either the latent variable or its distribution vary over randomly composed experimental groups. Second, the elementary response function is such that extensions to more complex cases (e.g., polychotomous responses, unfolding scales) are straightforward. Third, the probability metric of the latent trait allows tractable extensions to cover a wide variety of stochastic response processes. PMID- 26544973 TI - Lactobacillus acidophilus-Rutin Interplay Investigated by Proteomics. AB - Dietary polyphenols are bioactive molecules that beneficially affect human health, due to their anti-oxidant, anti-inflammatory, cardio-protective and chemopreventive properties. They are absorbed in a very low percentage in the small intestine and reach intact the colon, where they are metabolized by the gut microbiota. Although it is well documented a key role of microbial metabolism in the absorption of polyphenols and modulation of their biological activity, molecular mechanisms at the basis of the bacteria-polyphenols interplay are still poorly understood. In this context, differential proteomics was applied to reveal adaptive response mechanisms that enabled a potential probiotic Lactobacillus acidophilus strain to survive in the presence of the dietary polyphenol rutin. The response to rutin mainly modulated the expression level of proteins involved in general stress response mechanisms and, in particular, induced the activation of protein quality control systems, and affected carbohydrate and amino acid metabolism, protein synthesis and cell wall integrity. Moreover, rutin triggered the expression of proteins involved in oxidation-reduction processes.This study provides a first general view of the impact of dietary polyphenols on metabolic and biological processes of L. acidophilus. PMID- 26544975 TI - T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus. AB - BACKGROUND: T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE) has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification. METHODS: Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation. RESULTS: We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production. CONCLUSIONS: Unbiased transcriptome analysis of a peripheral blood component provides insight on autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction. PMID- 26544977 TI - Perioperative Nutritional Intervention: Where Are We? AB - As we look forward in 2015, attention to perioperative surgical nutrition continues to play a key role in optimizing outcomes and enhancing surgical recovery. Nutrition therapies for preoperative preparation include high protein intake combined with exercise, immune- and metabolic-modulating nutrients, carbohydrate loading, probiotic therapy and, occasionally, the need for specialized enteral or parenteral nutrition. Early enteral nutrition and probiotic therapy optimize gastrointestinal integrity and function in the postoperative setting. Some questions of who, when and how to optimally feed the surgical patient still exist. Despite these questions, the abundance of evidence supports a determined focus for nutrition optimization prior to major surgery. PMID- 26544976 TI - Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha Induced Inflammation in Human Umbilical Vein Endothelial Cells. AB - The AMP-activated protein kinase (AMPK) signaling system plays a key role in cellular stress by repressing the inflammatory responses induced by the nuclear factor-kappa B (NF-kappaB) system. Previous studies suggest that the anti inflammatory role of AMPK involves activation by adenine, but the mechanism that allows adenine to produce these effects has not yet been elucidated. In human umbilical vein endothelial cells (HUVECs), adenine was observed to induce the phosphorylation of AMPK in both a time- and dose-dependent manner as well as its downstream target acetyl Co-A carboxylase (ACC). Adenine also attenuated NF kappaB targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-alpha) treatment. The short hairpin RNA (shRNA) against AMPK alpha1 in HUVECs attenuated the adenine-induced inhibition of NF-kappaB activation in response to TNF-alpha, thereby suggesting that the anti-inflammatory role of adenine is mediated by AMPK. Following the knockdown of adenosyl phosphoribosyl transferase (APRT) in HUVECs, adenine supplementation failed to induce the phosphorylation of AMPK and ACC. Similarly, the expression of a shRNA against APRT nullified the anti inflammatory effects of adenine in HUVECs. These results suggested that the role of adenine as an AMPK activator is related to catabolism by APRT, which increases the cellular AMP levels to activate AMPK. PMID- 26544978 TI - Macronutrient Metabolism in Starvation and Stress. AB - In starvation and to a lesser extent in stress starvation, the loss of protein mass is spared as much as possible. This metabolic arrangement must have developed under the influence of evolutionary pressure in view of the importance of protein mass for function and longevity. Peripheral adipose tissue mass is only limiting when its mass is extremely small. Protein is the predominant precursor of glucose in (stress) starvation and glucose is an essential substrate for the synthesis and maintenance of cells and matrix and for the control of the redox state. To spare protein, glucose should be used efficiently only for those purposes that cannot be achieved by fat. It is suggested that this is achieved by limiting full glucose oxidation and increasing fatty acid and ketone body oxidation, which most likely can also largely cover energy needs of the central nervous system. In stress states, net negative nitrogen balance (catabolism) largely results from net losses of peripheral protein mass, predominantly muscles, whereas central organs (e.g. the liver), the immune system and wound healing are anabolic. A number of factors are responsible for a net negative nitrogen balance which may ultimately lead to death if stress persists. In stress, the amino acid mix derived from peripheral (predominantly muscle) tissues is modified in interplay with the liver and to a minor extent the kidney. This mix is different in nonstressed conditions, containing substantially increased amounts of the nonessential amino acids glutamine, alanine, glycine and (hydroxy)proline. Part of the amino acid skeletons released by muscles are substrates to produce glucose in the liver and kidney. Glucose and the amino acids produced especially serve as substrates for cell proliferation and matrix deposition. The catabolic processes in peripheral tissues cannot be countered completely by adequate nutritional support as long as stress persists. This metabolic arrangement dictates a nutritional mix containing liberal amounts of protein and carbohydrates and addition of lipids to cover energy requirements. PMID- 26544979 TI - Murid Gammaherpesvirus Latency-Associated Protein M2 Promotes the Formation of Conjugates between Transformed B Lymphoma Cells and T Helper Cells. AB - Establishment of persistent infection in memory B cells by murid herpesvirus-4 (MuHV-4) depends on the proliferation of latently infected germinal center B cells, for which T cell help is essential. Whether the virus is capable of modulating B-T helper cell interaction for its own benefit is still unknown. Here, we investigate if the MuHV-4 latency associated M2 protein, which assembles multiprotein complexes with B cell signaling proteins, plays a role. We observed that M2 led to the upregulation of adhesion and co-stimulatory molecules in transduced B cell lines. In an MHC-II restricted OVA peptide-specific system, M2 polarized to the B-T helper contact zone. Furthermore, it promoted B cell polarization, as demonstrated by the increased proximity of the B cell microtubule organizing center to the interface. Consistent with these data, M2 promoted the formation of B-T helper cell conjugates. In an in vitro competition assay, this translated into a competitive advantage, as T cells preferentially conjugated with M2-expressing B cells. However, expression of M2 alone in B cells was not sufficient to lead to T cell activation, as it only occurred in the presence of specific peptide. Taken together, these findings support that M2 promotes the formation of B-T helper cell conjugates. In an in vivo context this may confer a competitive advantage to the infected B cell in acquisition of T cell help and initiation of a germinal center reaction, hence host colonization. PMID- 26544980 TI - B-HIT - A Tool for Harvesting and Indexing Biodiversity Data. AB - With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups. PMID- 26544981 TI - An O-Methyltransferase Is Required for Infection of Tick Cells by Anaplasma phagocytophilum. AB - Anaplasma phagocytophilum, the causative agent of Human Granulocytic Anaplasmosis (HGA), is an obligately intracellular alpha-proteobacterium that is transmitted by Ixodes spp ticks. However, the pathogen is not transovarially transmitted between tick generations and therefore needs to survive in both a mammalian host and the arthropod vector to complete its life cycle. To adapt to different environments, pathogens rely on differential gene expression as well as the modification of proteins and other molecules. Random transposon mutagenesis of A. phagocytophilum resulted in an insertion within the coding region of an o methyltransferase (omt) family 3 gene. In wild-type bacteria, expression of omt was up-regulated during binding to tick cells (ISE6) at 2 hr post-inoculation, but nearly absent by 4 hr p.i. Gene disruption reduced bacterial binding to ISE6 cells, and the mutant bacteria that were able to enter the cells were arrested in their replication and development. Analyses of the proteomes of wild-type versus mutant bacteria during binding to ISE6 cells identified Major Surface Protein 4 (Msp4), but also hypothetical protein APH_0406, as the most differentially methylated. Importantly, two glutamic acid residues (the targets of the OMT) were methyl-modified in wild-type Msp4, whereas a single asparagine (not a target of the OMT) was methylated in APH_0406. In vitro methylation assays demonstrated that recombinant OMT specifically methylated Msp4. Towards a greater understanding of the overall structure and catalytic activity of the OMT, we solved the apo (PDB_ID:4OA8), the S-adenosine homocystein-bound (PDB_ID:4OA5), the SAH-Mn2+ bound (PDB_ID:4PCA), and SAM- Mn2+ bound (PDB_ID:4PCL) X-ray crystal structures of the enzyme. Here, we characterized a mutation in A. phagocytophilum that affected the ability of the bacteria to productively infect cells from its natural vector. Nevertheless, due to the lack of complementation, we cannot rule out secondary mutations. PMID- 26544983 TI - Temporal Genetic Variance and Propagule-Driven Genetic Structure Characterize Naturalized Rainbow Trout (Oncorhynchus mykiss) from a Patagonian Lake Impacted by Trout Farming. AB - Knowledge about the genetic underpinnings of invasions-a theme addressed by invasion genetics as a discipline-is still scarce amid well documented ecological impacts of non-native species on ecosystems of Patagonia in South America. One of the most invasive species in Patagonia's freshwater systems and elsewhere is rainbow trout (Oncorhynchus mykiss). This species was introduced to Chile during the early twentieth century for stocking and promoting recreational fishing; during the late twentieth century was reintroduced for farming purposes and is now naturalized. We used population- and individual-based inference from single nucleotide polymorphisms (SNPs) to illuminate three objectives related to the establishment and naturalization of Rainbow Trout in Lake Llanquihue. This lake has been intensively used for trout farming during the last three decades. Our results emanate from samples collected from five inlet streams over two seasons, winter and spring. First, we found that significant intra- population (temporal) genetic variance was greater than inter-population (spatial) genetic variance, downplaying the importance of spatial divergence during the process of naturalization. Allele frequency differences between cohorts, consistent with variation in fish length between spring and winter collections, might explain temporal genetic differences. Second, individual-based Bayesian clustering suggested that genetic structure within Lake Llanquihue was largely driven by putative farm propagules found at one single stream during spring, but not in winter. This suggests that farm broodstock might migrate upstream to breed during spring at that particular stream. It is unclear whether interbreeding has occurred between "pure" naturalized and farm trout in this and other streams. Third, estimates of the annual number of breeders (Nb) were below 73 in half of the collections, suggestive of genetically small and recently founded populations that might experience substantial genetic drift. Our results reinforce the notion that naturalized trout originated recently from a small yet genetically diverse source and that farm propagules might have played a significant role in the invasion of Rainbow Trout within a single lake with intensive trout farming. Our results also argue for proficient mitigation measures that include management of escapes and strategies to minimize unintentional releases from farm facilities. PMID- 26544984 TI - Identification of Esters as Novel Aggregation Pheromone Components Produced by the Male Powder-Post Beetle, Lyctus africanus Lesne (Coleoptera: Lyctinae). AB - Lyctus africanus is a cosmopolitan powder-post beetle that is considered one of the major pests threatening timber and timber products. Because infestations of this beetle are inconspicuous, damage is difficult to detect and identification is often delayed. We identified the chemical compounds involved in the aggregation behavior of L. africanus using preparations of crude hexanic extracts from male and female beetles (ME and FE, respectively). Both male and female beetles showed significant preferences for ME, which was found to contain three esters. FE was ignored by both the sexes. Further bioassay confirmed the role of esters in the aggregation behavior of L. africanus. Three esters were identified as 2-propyl dodecanoate, 3-pentyl dodecanoate, and 3-pentyl tetradecanoate. Further behavioral bioassays revealed 3-pentyl dodecanoate to play the main role in the aggregation behavior of female L. africanus beetles. However, significantly more beetles aggregated on a paper disk treated with a blend of the three esters than on a paper disk treated with a single ester. This is the first report on pheromone identification in L. africanus; in addition, the study for the first time presents 3-pentyl dodecanoate as an insect pheromone. PMID- 26544982 TI - Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate. AB - BACKGROUND: Evaluation of candidates to serve as living kidney donors relies on screening for individual risk factors for end-stage renal disease (ESRD). To support an empirical approach to donor selection, we developed a tool that simultaneously incorporates multiple health characteristics to estimate a person's probable long-term risk of ESRD if that person does not donate a kidney. METHODS: We used risk associations from a meta-analysis of seven general population cohorts, calibrated to the population-level incidence of ESRD and mortality in the United States, to project the estimated long-term incidence of ESRD among persons who do not donate a kidney, according to 10 demographic and health characteristics. We then compared 15-year projections with the observed risk among 52,998 living kidney donors in the United States. RESULTS: A total of 4,933,314 participants from seven cohorts were followed for a median of 4 to 16 years. For a 40-year-old person with health characteristics that were similar to those of age-matched kidney donors, the 15-year projections of the risk of ESRD in the absence of donation varied according to race and sex; the risk was 0.24% among black men, 0.15% among black women, 0.06% among white men, and 0.04% among white women. Risk projections were higher in the presence of a lower estimated glomerular filtration rate, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. In the model-based lifetime projections, the risk of ESRD was highest among persons in the youngest age group, particularly among young blacks. The 15-year observed risks after donation among kidney donors in the United States were 3.5 to 5.3 times as high as the projected risks in the absence of donation. CONCLUSIONS: Multiple demographic and health characteristics may be used together to estimate the projected long-term risk of ESRD among living kidney-donor candidates and to inform acceptance criteria for kidney donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.). PMID- 26544985 TI - Association of a Dietary Score with Incident Type 2 Diabetes: The Dietary-Based Diabetes-Risk Score (DDS). AB - BACKGROUND: Strong evidence supports that dietary modifications may decrease incident type 2 diabetes mellitus (T2DM). Numerous diabetes risk models/scores have been developed, but most do not rely specifically on dietary variables or do not fully capture the overall dietary pattern. We prospectively assessed the association of a dietary-based diabetes-risk score (DDS), which integrates optimal food patterns, with the risk of developing T2DM in the SUN ("Seguimiento Universidad de Navarra") longitudinal study. METHODS: We assessed 17,292 participants initially free of diabetes, followed-up for a mean of 9.2 years. A validated 136-item FFQ was administered at baseline. Taking into account previous literature, the DDS positively weighted vegetables, fruit, whole cereals, nuts, coffee, low-fat dairy, fiber, PUFA, and alcohol in moderate amounts; while it negatively weighted red meat, processed meats and sugar-sweetened beverages. Energy-adjusted quintiles of each item (with exception of moderate alcohol consumption that received either 0 or 5 points) were used to build the DDS (maximum: 60 points). Incident T2DM was confirmed through additional detailed questionnaires and review of medical records of participants. We used Cox proportional hazards models adjusted for socio-demographic and anthropometric parameters, health-related habits, and clinical variables to estimate hazard ratios (HR) of T2DM. RESULTS: We observed 143 T2DM confirmed cases during follow up. Better baseline conformity with the DDS was associated with lower incidence of T2DM (multivariable-adjusted HR for intermediate (25-39 points) vs. low (11 24) category 0.43 [95% confidence interval (CI) 0.21, 0.89]; and for high (40-60) vs. low category 0.32 [95% CI: 0.14, 0.69]; p for linear trend: 0.019). CONCLUSIONS: The DDS, a simple score exclusively based on dietary components, showed a strong inverse association with incident T2DM. This score may be applicable in clinical practice to improve dietary habits of subjects at high risk of T2DM and also as an educational tool for laypeople to help them in self assessing their future risk for developing diabetes. PMID- 26544986 TI - Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel. AB - Transient receptor potential melastatin-1 (TRPM1) is a calcium channel that is essential for the depolarization of photo-responsive retinal bipolar cells, but most of the physiological functions and cellular roles of this channel are still poorly understood. Most transient receptor potential (TRP) channels are typically regulated by intracellular proteins and other signaling molecules. Phosphatidylinositol-4,5 bisphosphate (PIP2), a minor phospholipid component of cell membranes, has previously been shown to directly bind TRP channels and to play a unique role in modulating receptor function. To characterize the binding of PIP2 as a potential regulator of TRPM1, we utilized biophysical methods and molecular modeling to study the interactions of PIP2 with an N-terminal fragment of TRPM1 (residues A451-N566). The basic N-terminal residue K464 of TRPM1 suggests that it is part of putative pleckstrin homology (PH) domain and is involved in the interactions with PIP2. This is the first report detailing the binding of PIP2 at the N-terminus of the TRPM1 receptor. PMID- 26544987 TI - Pharmacokinetics of Posaconazole Oral Suspension in Children Dosed According to Body Surface Area. AB - BACKGROUND: Antifungal prophylaxis remains challenging in immunocompromised children as no clear consensus has yet been reached about which drug to be used. Posaconazole has a broad spectrum of activity, a favorable safety profile and excellent prophylactic activity in adults. However, a lack of pharmacokinetic studies in pediatric patients hampers routine implementation. This study investigates the pharmacokinetics of a newly introduced posaconazole dosing regimen based on the body surface area in pediatric hematologic patients. METHODS: In this prospective pharmacokinetic study, 8 blood samples were taken during 1 dosing interval at steady state in children aged 13 years or younger with hematologic malignancy, who were treated prophylactically with posaconazole oral suspension at a dose of 120 mg/m 3 times daily. Posaconazole plasma concentrations were determined using high-performance liquid chromatography fluorescence detection. RESULTS: One hundred twelve samples were taken from 14 patients with a mean age of 6.7 +/- 2.8 years. A median posaconazole daily dose of 100.0 mg (77.3-100.0) 3 times daily (tid), corresponding to a median of 117.9 mg/m (112.2-120.4) tid, resulted in mean trough posaconazole plasma concentrations of 0.85 +/- 0.56 mg/L. Pharmacokinetic analysis revealed a clearance of 0.8 L/(h kg) (0.5-1.4). No invasive fungal infections or adverse events were encountered during treatment. CONCLUSIONS: Posaconazole is a promising antifungal agent to be used prophylactically in hematologic patients aged 13 years or younger. Administering posaconazole oral suspension in a dosage of 120 mg/m tid results in adequate posaconazole plasma exposure, without significant adverse events. PMID- 26544988 TI - Clinical Impact of beta-Lactamase-producing Enterobacteriaceae in Sputum of Cystic Fibrosis Patients. AB - This case series describes 18 cystic fibrosis (CF) patients of a 135-patient CF center cohort with extended spectrum beta-lactamase-producing Enterobacteriaceae, from 2003 to 2012. Four had chronic infection. Prevalence increased annually from 0 to 6.35%. Risk factors compared with the 2010 CF center cohort included continuous inhaled antibiotics (P = 0.014) and courses of intravenous antibiotics during the year before first isolation (P = 0.009). Hospitalization rates were 1.05/year and 0.47/year preinfection and postinfection, respectively (P = 0.02). Slope of forced expiratory volume at 1 second% predicted remained unchanged during 12 months. PMID- 26544989 TI - Complications of Varicella in Unvaccinated Children From Romania, 2002-2013: A Retrospective Study. AB - The epidemiologic and clinical pattern of varicella-related hospitalizations recorded during 2002-2013 in Romania showed the highest hospitalization rate in the 0-1 year age group. Younger age and diagnosis after 2007 were independent predictors of varicella-related complications, recorded in half of the hospitalized cases. PMID- 26544990 TI - Versatile Method for Producing 2D and 3D Conductive Biomaterial Composites Using Sequential Chemical and Electrochemical Polymerization. AB - Flexible and conductive biocompatible materials are attractive candidates for a wide range of biomedical applications including implantable electrodes, tissue engineering, and controlled drug delivery. Here, we demonstrate that chemical and electrochemical polymerization techniques can be combined to create highly versatile silk-conducting polymer (silk-CP) composites with enhanced conductivity and electrochemical stability. Interpenetrating silk-CP composites were first generated via in situ deposition of polypyrrole during chemical polymerization of pyrrole. These composites were sufficiently conductive to serve as working electrodes for electropolymerization, which allowed an additional layer of CP to be deposited on the surface. This sequential method was applied to both 2D films and 3D sponge-like silk scaffolds, producing conductive materials with biomimetic architectures. Overall, this two-step technique expanded the range of available polymers and dopants suitable for the synthesis of mechanically robust, biocompatible, and highly conductive silk-based materials. PMID- 26544991 TI - [In Process Citation]. PMID- 26544992 TI - [In Process Citation]. PMID- 26544993 TI - [In Process Citation]. PMID- 26544994 TI - [In Process Citation]. PMID- 26544995 TI - [In Process Citation]. PMID- 26544996 TI - [In Process Citation]. PMID- 26544997 TI - [Mexico keeps backing up with evidence its nutrition interventions]. PMID- 26544998 TI - Nutritional status of iron, vitamin B12, folate, retinol and anemia in children 1 to 11 years old: Results of the Ensanut 2012. AB - OBJECTIVE: To describe the frequency of anemia, iron, vitamin B12, folate, retinol and predictors of anemia among Mexican children from Ensanut 2012. MATERIALS AND METHODS: Hemoglobin, ferritin, CRP, vitamin B12, retinol and folate concentrations were measured in 2 678 children aged 1-4 y and 4 275 children aged 5-11 y. Adjusted logistic regression models were constructed to assess the risk for anemia and micronutrient deficiencies. RESULTS: In preschoolers and scholars, the overall prevalence of anemia was 20.4 and 9.7%, iron deficiency 14 and 9.3%, low vitamin B12 (LB12S) 1.9 and 2.6%; Folate 0.30 and 0%, and retinol depletion (VADp) 15.7 and 2.3%, respectively. ID and VADp were negatively associated with Hb (coefficient: -0.38 and -0.45, p<0.05); a higher log-CRP was associated with higher risk for anemia and VADp (OR=1.13 and OR=2.1, p<0.05, respectively). CONCLUSIONS: Iron deficiency, anemia and VADp are some of the main nutritional problems among Mexican infants. PMID- 26544999 TI - Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012. AB - OBJECTIVE: To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. MATERIALS AND METHODS: Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. RESULTS: The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). CONCLUSIONS: The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies. PMID- 26545000 TI - Anemia and iron deficiency in Mexican elderly population: Results from the Ensanut 2012. AB - OBJECTIVE: To describe de prevalence of iron deficiency (ID) and anemia in a sample of Mexican elderly population from the National Health and Nutrition Survey (Ensanut) 2012. MATERIALS AND METHODS: 1 920 subjects >=60 years of age were included. Hemoglobin, serum concentrations of ferritin and CRP were measured. The risk for ID and anemia adjusted for potential confounders was assessed in logistic regression models. RESULTS: The overall prevalence of anemia was 13.9%, 15.2% in males and 12.8% females. For ID, overall it was 4.2%, males 4.0% and females 4.3%. The greatest prevalence of ID was found in males and females over 80 years old (6.9 and 7.0%, respectively). ID was present in 1.5 of 10 Mexican elders with anemia. CONCLUSION: The prevalence of anemia was high in the elderly, however the prevalence of ID was low; there is a need to further investigate the causes of anemia in this age group. PMID- 26545001 TI - Assessing the physical activity environment in Mexican healthcare settings. AB - OBJECTIVE: To assess the informational, educational and instrumental environments among Mexican healthcare settings for their potential to promote physical activity (PA). MATERIALS AND METHODS: The Environmental Physical Activity Assessment Tool for Healthcare Settings (EPATHS) was developed to assess the PA environments of 40 clinics/hospitals representing the three Mexican healthcare systems in Guadalajara. The EPATHS assessed the presence and quality of PA enhancing features in the informational (e.g. signage), educational (e.g. pamphlets), and instrumental (e.g. stairs) environments of included clinics/hospitals. RESULTS: 28 (70%) clinics/hospitals had more than one floor with stairs; 60% of these had elevators. Nearly 90% of stairs were visible, accessible and clean compared to fewer than 30% of elevators. Outdoor spaces were observed in just over half (55%) of clinics/hospitals, and most (70%) were of good quality. Only 25% clinics/hospitals had educational PA materials. CONCLUSIONS: The PA instrumental environment of Mexican healthcare settings is encouraging. The informational and educational environments could improve. PMID- 26545002 TI - Risk factors for extended-spectrum beta-lactamases-producing Escherichia coli urinary tract infections in a tertiary hospital. AB - OBJECTIVE: To assess the risks factors for urinary tract infections (UTIs) caused by Extended-Spectrum Beta-Lactamases (ESBLs)-producing E. coli and the molecular characterization of ESBLs. MATERIALS AND METHODS: A case-control study was performed to identify risk factors in consecutively recruited patients with UTIs caused by ESBLs or non-ESBLs-producing E. coli in a tertiary hospital in Mexico. RESULTS: ESBLs-producing E. coli were isolated from 22/70 (31%) patients with E. coli UTIs over a three month period. All isolates were resistant to cephalosporins and quinolones but susceptible to carbapenems, amikacin and nitrofurantoin. Prior antibiotic treatment with more than two antibiotic families (OR=6.86; 95%CI 1.06-157.70; p=0.028), recurrent symptomatic UTIs (OR=5.60; 95%CI 1.88-17.87; p=0.001) and previous hospitalization (OR=5.06; 95%CI 1.64-17.69; p=0.002) were significant risk factors. Sixteen isolates harbored the beta lactamase (bla)CTX-M-15 gene and five the blaTEM-1 gene. CONCLUSIONS: One of every three patients presented UTIs with ESBLs-producing beta-lactams and fluoroquinolone resistant E. coli. Risk factors and resistance patterns must be taken into account for developing antibiotic use policies in these settings. PMID- 26545003 TI - [Evaluation of a reduced panel of leptospira strains for microagglutination]. AB - OBJECTIVE: To evaluate if the use of the 19 Leptospira strains panel suggested by the International Leptospirosis Society of World Health Organization for microagglutination allows confirmation of more cases that the 12 strains panel used in Argentina. MATERIALS AND METHODS: Cross-sectional observational study. We studied 441 serum samples corresponding to Argentinean patients with suspected leptospirosis derived during from July to December, 2009 and from January to October, 2013. RESULTS: The same number of positive samples was obtained using the MAT with the 19 or 12 strains. In six cases a serovar of the expanded collection was presumably infecting, but always coagglutinated with strains of the reduced panel. CONCLUSION: In Argentina, the diagnosis of leptospirosis by MAT could be made using the reduced 12 strains panel, obtaining the same result in case detection as using the 19 strains panel. Additional information provided by the use of all strains could be the presumably infecting serogroup. PMID- 26545004 TI - [The cost impact of a private insurer's own network upon outpatient care]. AB - OBJECTIVE: Econometric analysis that seeks to measure the cost impact of a private insurer's own network upon outpatient care for its policyholders, own network refers to vertical integrated providers. The purpose is to assess whether greater use of its own network reduces the costs that the insurer incurred, according to what specialized literature suggests. MATERIALS AND METHODS: Study based on a multiple linear regression on data from a private insurer. The dependent variable is per capita cost of outpatient services. The explanatory variables are adherence to the own network and a number of variables to specify better the model. RESULTS: With all other factors constant, in relation to covering the costs of outpatient care, it is noted that policyholders with high adhesion to their own network are less expensive than whose with low adhesion. CONCLUSIONS: The decision-making process about what services and what grade should be applied to each person by special conditions of the offer as the aggregation of human resources in own offices under formal rules has an impact on health care costs. Particular supply conditions cause variations in how resources are used. PMID- 26545005 TI - [Challenges of the right to health in the Colombian model]. AB - Health in Colombia is now a fundamental right that has to be provided and protected by the government. We evaluated the strengths and difficulties of the health system with respect to the statutory law enacted in February 2015, using methodologies for analysis of health systems proposed by the WHO and the World Bank. The challenges include the fragmentation and specialization of services, access barriers and incentives that are not aligned with the quality, weak governance, multiple actors with little coordination and information system that does not measure results. The government needs to find a necessary social agreement, a balance between the particular and the collective benefit. PMID- 26545006 TI - [Global health 2035: implications for Mexico (commentary)]. PMID- 26545008 TI - [Dr. Carlos J. Finlay (1833-1915): on the centenary of his decease]. PMID- 26545007 TI - [Global health 2035: a world converging within a generation]. AB - Prompted by the 20th anniversary of the 1993 World Development Report, a Lancet Commission revisited the case for investment in health and developed a new investment framework to achieve dramatic health gains by 2035. The Commission's report has four key messages, each accompanied by opportunities for action by national governments of low-income and middle-income countries and by the international community. First, there is an enormous economic payoff from investing in health. The impressive returns make a strong case for both increased domestic financing of health and for allocating a higher proportion of official development assistance to development of health. Second, modeling by the Commission found that a "grand convergence" in health is achievable by 2035-that is, a reduction in infectious, maternal, and child mortality down to universally low levels. Convergence would require aggressive scale up of existing and new health tools, and it could mostly be financed from the expected economic growth of low- and middle-income countries. The international community can best support convergence by funding the development and delivery of new health technologies and by curbing antibiotic resistance. Third, fiscal policies -such as taxation of tobacco and alcohol- are a powerful and underused lever that governments can use to curb non-communicable diseases and injuries while also raising revenue for health. International action on NCDs and injuries should focus on providing technical assistance on fiscal policies, regional cooperation on tobacco, and funding policy and implementation research on scaling-up of interventions to tackle these conditions. Fourth, progressive universalism, a pathway to universal health coverage (UHC) that includes the poor from the outset, is an efficient way to achieve health and financial risk protection. For national governments, progressive universalism would yield high health gains per dollar spent and poor people would gain the most in terms of health and financial protection. The international community can best support countries to implement progressive UHC by financing policy and implementation research, such as on the mechanics of designing and implementing evolution of the benefits package as the resource envelope for public finance grows. PMID- 26545011 TI - Differential effects of traffic sign stimuli upon speeding in school zones following a traffic light interruption. AB - Motorists whose journey has been interrupted by signalized traffic intersections in school zones resume their journey at a faster vehicle speed than motorists who have not been required to stop. Introducing a flashing "check speed" sign 70m after the traffic intersections counteracts this interruptive effect. The present study examined which aspects of a reminder sign are responsible for reducing the speeding behavior of interrupted motorists. When a sign that combines both written text and flashing lights was introduced, interrupted motorists did not speed, traveling on average 0.82km/h below the 40km/h speed limit when measured 100m from traffic intersections. Alternatively, when only the flashing lights were visible the interrupted motorists sped 3.36km/h over the 40km/h speed limit. Similar vehicular speeds were observed when only the written text was visible and when no sign was present (7.67 and 7.49km/h over the 40km/h speed limit, respectively). This indicates that static reminder signs add little value over the absence of a school zone reminder sign; the presence of both cues is necessary to fully offset the interruptive effect. This study also highlights the benefit of using exogenous visual cues in traffic signs to capture drivers' attention. These findings have practical implications for the design and use of traffic signs to increase compliance with posted speed limits. PMID- 26545012 TI - Apolipoprotein E-deficient rats develop atherosclerotic plaques in partially ligated carotid arteries. AB - BACKGROUND: The goal of this study was to establish an apolipoprotein E-deficient (ApoE(-/-)) rat model. METHODS: The ApoE(-/-) rat was created by TALEN-mediated gene targeting in the genetic background of Sprague Dawley rat. Six-to eight-week old male rats were used in the experiments (n = 10 in each group). RESULTS: After fed with high-cholesterol diet (HCD) for 12 weeks, the ApoE(-/-) rats displayed typical dyslipidemia. In contrast, HCD failed to induce hypercholesterolemia in wild-type rats. However, there was no obvious atherosclerotic lesion in oil red O stained en face aortas and the aortic root sections in both genetic types of rats. Interestingly, partial ligation caused the formation of plaques consist of lipid and macrophages in carotid arteries from ApoE(-/-) rats, but induced the neointimal hyperplasia in wild-type rats. Additionally, we found that HCD slightly increased the expression of adhesion molecules, while partial ligation dramatically upregulated these molecules. CONCLUSIONS: The ApoE(-/-) rat is a novel model for dyslipidemia and could also be used in the research of atherosclerosis. PMID- 26545013 TI - Atherosclerosis stabilization with PCSK-9 inhibition: An evolving concept for cardiovascular prevention. AB - Monoclonal antibodies (mAbs) to proprotein convertase subtilisin/kexin type 9 (PCSK-9) can further lower LDL-C by >=60% in statin-treated patients. Preliminary data suggest they may reduce cardiovascular (CVD) events. Ongoing PCSK-9 mAb cardiovascular outcomes trials could provide the opportunity to determine whether a "legacy effect" similar to that observed for statins will occur over the post trial observation period. We hypothesize these trials could demonstrate that (1) very aggressive LDL-C lowering with PCSK-9 mAbs added to background statin therapy will induce extensive atherosclerosis stabilization and regression in the large majority of treated patients, and (2) continued maintenance therapy with high intensity statin therapy (with or without ezetimibe) should then inhibit new plaque formation, with a long-term prevention of CVD events. The necessity of expensive lifetime treatment with PCSK-9 inhibitors could then be avoided in all but a small subset of patients who could benefit from longer treatment. PMID- 26545014 TI - Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1 deficient mice. AB - BACKGROUND AND AIM: We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. METHODS AND RESULTS: Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. CONCLUSION: Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. PMID- 26545015 TI - Infectious diseases are associated with carotid intima media thickness in adolescence. AB - OBJECTIVE: Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence. STUDY DESIGN: 288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex. RESULTS: Youth (mean age 14.8 yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported >=3 infectious diseases (p = 0.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p = 0.567). Sex-stratified analyses yielded significantly increased CIMT in boys with >=3 infectious diseases vs. none (0.046 mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011 mm, 95%CI -0.015; 0.036). CONCLUSION: The SAPALDIA Youth study complements current evidence on infectious origins of atherosclerosis in adults. The larger effects observed in boys may relate to a higher vulnerability of the vasculature and/or to infectious pathogens. Our data are suggestive of an early impact of childhood infectious diseases on vascular health. PMID- 26545016 TI - Synthesis and evaluation of Lys1(alpha,gamma-Folate)Lys3(177Lu-DOTA)-Bombesin(1 14) as a potential theranostic radiopharmaceutical for breast cancer. AB - The aim of this work was to synthesize Lys(1)(alpha,gamma-Folate)-Lys(3)((177)Lu DOTA)-Bombesin (1-14) ((177)Lu-Folate-BN), as well as to assess its potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (FR) and gastrin-releasing peptide receptors (GRPR). Radiation absorbed doses of (177)Lu-Folate-BN (74 MBq, i.v.) estimated in athymic mice with T47D induced breast tumors (positive to FR and GRPR), showed tumor doses of 23.9+/-2.1 Gy. T47D-tumors were clearly visible (Micro-SPECT/CT images). (177)Lu-Folate-BN demonstrated properties suitable as a theranostic radiopharmaceutical. PMID- 26545017 TI - Value of 18F-FDG PET/CT for Predicting the World Health Organization Malignant Grade of Thymic Epithelial Tumors: Focused in Volume-Dependent Parameters. AB - PURPOSE: We investigated whether preoperative parameters of 18F-FDG PET/CT were correlated with the World Health Organization (WHO) classification and/or Masaoka staging of thymic epithelial tumors. PATIENTS AND METHODS: We reviewed 61 patients retrospectively who were diagnosed with thymic epithelial tumors after surgical resection and PET/CT. A volume of interest was drawn on the primary lesion, using an SUV cutoff of 2.5, and metabolic indices such as SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. RESULTS: There were 24 male patients (38.7%), and the mean (SD) age was 50.23 (12.54) years. The mean (SD) tumor size was 6.11 (3.41) cm. There were 22 low risk thymomas (36.9%) (A, AB, B1), 32 high-risk thymomas (51.6%), and 7 thymic carcinomas (11.5%). The Masaoka stage was I in 15 (24.6%), II in 30 (49.2%), III in 11 (18.0%), and IV in 5 patients (8.2%). Mean (SD) SUVmax was 3.43 (1.01) in low-risk thymomas, 4.42 (1.70) in high-risk thymomas, and 8.23 (2.61) in thymic carcinoma; the differences were significant (P < 0.001). Mean (SD) MTV and TLG were 90.74 (114.56) and 229.36 (300.56) in low-risk thymomas, 80.82 (112.49) and 233.93 (340.91) in high-risk thymomas, and 90.63 (90.74) and 390.94 (437.62), respectively, in thymic carcinomas. MTV and TLG showed no correlation with the WHO classification. On receiver operating characteristic curve analysis, the cutoff value for discriminating thymomas and thymic carcinomas was 5.05. SUVmax and TLG were correlated with Masaoka stage. CONCLUSIONS: Although volume dependent parameters were not correlated with the WHO classification, a significant relationship was observed between SUVmax and WHO classification and Masaoka stage. PMID- 26545018 TI - Follow-up FDG PET/CT in Patients With Non-Hodgkin Lymphoma: Value to Clinical Assessment and Patient Management. AB - OBJECTIVE: The aim of this study was to evaluate the value of each follow-up PET/CT in the clinical assessment of recurrence as well as determining its impact on management in patients with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: All patients diagnosed with NHL who had at least 1 follow-up PET/CT study, 6 months after primary treatment completion, were included. There were 204 eligible NHL patients with 560 follow-up PET/CT scans. The change in management was recorded after each follow-up PET/CT scan in comparison to the management plan before the study. RESULTS: Among the 560 scans, 388 scans (69.3%) were done without clinical suspicion and 172 scans (30.7%) were done with prior clinical suspicion of recurrence. Follow-up scan results suggested disease in 12.4% of the scans performed without clinical suspicion and ruled out disease in 16.3% scans performed with prior clinical suspicion. The management of NHL patients was changed after 37.8% of follow-up scans with prior clinical suspicion of recurrence and after 8.3% of scans in patients without prior clinical suspicion of recurrence. The management of NHL patients was not changed after 50.6% scans with prior clinical suspicion of recurrence of which 23.3% had no treatment before and after the scan and 27.3% had the same treatment continued before and after the scan. CONCLUSIONS: Follow-up FDG PET/CT performed with prior clinical suspicion of recurrence added value to patients with NHL for clinical assessment in 16.3% of the scan times and influenced the management in 37.8% of scan times. The management change was only 8.3% in patients without prior clinical suspicion of recurrence, and hence, surveillance FDG PET/CT in NHL should be avoided. PMID- 26545019 TI - Quality and Safety in Health Care, Part VII: Lower Costs and Higher Quality. AB - The Institute of Medicine report entitled The Health Care Imperative: Lowering Costs and Improving Outcomes discussed numerous ways to decrease costs in the health care system without decreasing quality. The use of evidence-based medicine, eliminating wasteful spending such as needlessly high administrative costs, having more preventive services, having a better reimbursement system that emphasized quality, developing a less fragmented and more efficient medical delivery system, having more transparency for patients on the outcomes of different providers, having greater health care literacy for patients, and eliminating fraud were some of the recommendations. The total savings from eliminating unnecessary health care costs was estimated to be over 3 quarters of a trillion dollars each year. PMID- 26545020 TI - Focally Increased FDG Activity in the Liver Related to Hydropic Degeneration. AB - A 50-year-old man, who had diffuse large B-cell lymphoma in the neck and just finished 4 cycles of chemotherapy, presented to our department to evaluate the status of the disease. FDG PET/CT revealed a focally increased activity in the right lobe of the liver. However, pathological examination showed hepatocyte hydropic degeneration with associated inflammatory cells without evidence of malignancy. PMID- 26545021 TI - Enhanced CT and FDG PET/CT in Histiocytic Sarcoma of the Pericardium. AB - Histiocytic sarcoma is an extremely rare and aggressive malignant neoplasm of presumed hematopoietic origin. Lymph nodes are the most common sites of involvement. A variety of extranodal sites can be involved, particularly the gastrointestinal tract, soft tissue, skin, and spleen. Radiologic findings of histiocytic sarcoma have been rarely reported. We present a case with histiocytic sarcoma in pericardium, which is an unusual site. Enhanced chest CT showed remarkable enhancement of the tumor. On FDG PET/CT, the tumor showed intense FDG uptake. PMID- 26545022 TI - 18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab. AB - Pembrolizumab is an anti-programmed cell death receptor 1 (anti-PD-1) antibody, recently approved for the treatment of ipilimumab-refractory metastatic melanoma. We report on a 49-year-old patient with unresectable metastatic melanoma initially treated with 4 cycles of ipilimumab. Because of demonstration of progressive disease on PET/CT, the patient was enrolled into a clinical trial of pembrolizumab. After completion of 4 cycles of pembrolizumab, the follow-up PET/CT scans performed early after and 7 months after the end of treatment exhibited complete disease remission, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving anti-PD 1 therapy. PMID- 26545023 TI - Added Value of SPECT/CT in the Evaluation of Benign Bone Diseases of the Appendicular Skeleton. AB - Bone scintigraphy is a sensitive technique to detect altered bone mineralization but has limited specificity. The use of SPECT/CT has improved significantly the diagnostic accuracy of bone scintigraphy, in patients with cancer as well as in evaluation of benign bone disease. It provides precise localization and characterization of tracer-avid foci, shortens the diagnostic workup, and decreases patient anxiety. Through both the SPECT and the CT components, SPECT/CT has an incremental value in characterizing benign bone lesions, specifically in the appendicular skeleton, as illustrated by present case series. PMID- 26545024 TI - 18F-FDG PET in Liver Transplantation Setting of Hepatocellular Carcinoma: Predicting Histology? AB - PURPOSE: The aim of this study was to evaluate the prognostic value of F-FDG PET/CT by predicting histopathological findings in the pretransplant evaluation of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: F-FDG PET/CT findings of 34 patients with HCC who underwent liver transplantation were reviewed retrospectively. Visual and quantitative analysis (tumor standardized uptake values normalized to the background activity of the liver: SUVmax T/L) was done. PET tumor characteristics were compared with the histological analysis (differentiation and microvascular invasion). All patients were followed up (mean, 12 months). RESULTS: Ten patients showed tumoral uptake greater than background activity (PET+). Higher-grade tumor was more common in the F-FDG-avid tumor group (P < 0.05). PET+ also showed more microvascular invasion at explant pathology (P < 0.05). Only 1 patient PET+ developed HCC early recurrence (4 months) with an SUVmax T/L of 1.64. CONCLUSIONS: F-FDG uptake is predictive for microvascular invasion and tumor differentiation. This examination has a prognostic value regarding tumor recurrence after liver transplantation for HCC. PMID- 26545025 TI - 18F-FDG PET/CT Brain Imaging on a Patient With Paraneoplastic Opsoclonus Myoclonus Syndrome Arising out of a Mature Cystic Teratoma. AB - Opsoclonus-myoclonus syndrome (OMS) is an involuntary multidirectional eye movement accompanied by myoclonic jerks and a subtype of paraneoplastic neurological syndromes. Clinical features of OMS include opsoclonus with myoclonic jerks and cerebellar ataxia. Although there have been a few studies on brain FDG PET in paraneoplastic neurological syndrome associated with some kinds of malignancies such as lung and gastric cancer, brain FDG PET of patients with OMS caused by a mature cystic teratoma has not been reported. Here, we described a case of brain FDG PET/CT studies performed in a woman with OMS provoked from a mature cystic teratoma. PMID- 26545026 TI - Retrosternal Goiter Visualized on 99mTc Pertechnetate SPECT/CT, But Not on Planar Scintigraphy. AB - Retrosternal goiter is one of the common causes of anterior mediastinal masses. Scintigraphic diagnosis of retrosternal goiter plays an important role in avoiding invasive diagnostic procedures, and SPECT acquisition may enhance the diagnostic sensitivity of this technique as compared with planar scintigraphy. Here, I report a case of retrosternal goiter that was demonstrated on SPECT/CT obtained with Tc pertechnetate, but not on planar scintigraphy with the same tracer. PMID- 26545027 TI - Preliminary Comparison of PET/CT Studies Performed After Intravenous and Oral Administration of 18F-Fluoride. AB - A 78-year-old man with prostate cancer was referred for 18F-NaF PET/CT for assessing bone metastases. An 18F-NaF PET/CT study was performed after the intravenous administration of the radiopharmaceutical. Five days later, a second study was done after oral administration of the radiopharmaceutical as part of a research protocol. PMID- 26545028 TI - Detection of Leptomeningeal Involvement by 18F-FDG-PET/CT in a Patient With Non Hodgkin Lymphoma. AB - Leptomeningeal infiltration of the brain or spinal cord by neoplastic cells may occur as complication of solid or hematopoietic tumors such as non-Hodgkin lymphoma. Previously rare, this event is becoming increasingly common as newer therapies can prolong survival but may not achieve therapeutic concentration in the central nervous system. Although prognosis is poor, early diagnosis and aggressive treatment may lead to prolonged survival and/or improvement of quality of life. We report a case of a 69-year-old man with leptomeningeal infiltration by non-Hodgkin lymphoma revealed by F-FDG-PET/CT and confirmed by subsequent spinal MRI and cerebrospinal fluid cytology. PMID- 26545029 TI - Computational Exposure Science: An Emerging Discipline to Support 21st-Century Risk Assessment. AB - BACKGROUND: Computational exposure science represents a frontier of environmental science that is emerging and quickly evolving. OBJECTIVES: In this commentary, we define this burgeoning discipline, describe a framework for implementation, and review some key ongoing research elements that are advancing the science with respect to exposure to chemicals in consumer products. DISCUSSION: The fundamental elements of computational exposure science include the development of reliable, computationally efficient predictive exposure models; the identification, acquisition, and application of data to support and evaluate these models; and generation of improved methods for extrapolating across chemicals. We describe our efforts in each of these areas and provide examples that demonstrate both progress and potential. CONCLUSIONS: Computational exposure science, linked with comparable efforts in toxicology, is ushering in a new era of risk assessment that greatly expands our ability to evaluate chemical safety and sustainability and to protect public health. CITATION: Egeghy PP, Sheldon LS, Isaacs KK, Ozkaynak H, Goldsmith M-R, Wambaugh JF, Judson RS, Buckley TJ. 2016. Computational exposure science: an emerging discipline to support 21st-century risk assessment. Environ Health Perspect 124:697-702; http://dx.doi.org/10.1289/ehp.1509748. PMID- 26545030 TI - Visual Display Terminal use in Iranian bank tellers: Effects on job stress and insomnia. AB - BACKGROUND: Visual Display Terminals (VDTs) are equipments in many workplaces which their use may increase the risk of visual, musculoskeletal and mental problems including insomnia. OBJECTIVE: To determine the relationship between duration of daily VDT use and insomnia among the Iranian bank tellers. METHODS: We randomly selected 382 bank tellers working with VDT. Quality of sleep and stress information were collected by Athens Insomnia Scales (AIS) and Demand Control Model (DCM) model respectively. RESULTS: Out of 382 participants, 127 (33.2%) had sleep complaints and 255 (66.8%) had no sleep disorders. Moreover, the insomnia symptoms' score were significantly high in the participants having more than 6 hours of daily VDT use after adjusting for multiple confounding factors (P < 0.001). There was no significant relationship between stress and insomnia. CONCLUSIONS: It seems that the low levels of stress and job satisfaction reduce the impact of VDT on sleep quality in tellers who worked less than 6 hours per day. PMID- 26545031 TI - Engage/Trojan Neighbors: A community service partnership between an academic division and residential community. AB - This paper describes the case of an after-school program, focused on providing enrichment opportunities for neighborhood youth, jointly administered through an academic division and residential community within a large urban research university. The program, originally conceived as an activity-based after-school program for middle school youth, expanded in scope in response to both community and student needs. The resident faculty fellow in this community served as a liaison between the academic division and office of residential education, helping maintain continuity and facilitating effective student leadership of the program. In this case, we detail the origins and evolution of the program, including strategies used to resolve challenges that arose over several years of program implementation. PMID- 26545033 TI - From the Editor. PMID- 26545032 TI - Service intangibility and its implications for the work coordination of primary healthcare multi-professional teams in Brazil. AB - BACKGROUND: In certain service activities, the intangibility of what is being produced hinders the vision of an expected result or product. In multi professional teams, this difficulty becomes increasingly greater, as participants' perceptions are conditioned to their respective fields of knowledge and different professional experiences. This is a common situation in healthcare services. OBJECTIVE: To describe and explain the work coordination process applied by multi-professional teams in order to deal with the intangibility inherent in the healthcare services. METHODS: This study involved six multi professional teams from the public primary healthcare service in Brazil. Interviews and observations of team meetings were carried out, with focus on the critical elements of a coordination process: work plans and routines, roles and responsibilities, knowledge sharing, and a common reference history. RESULTS: There is coexistence of two distinct coordination processes being performed in the same work activity: operational coordination, associated with activities that somehow follow standard procedures; and diagnostic coordination, associated with diagnosis construction, alternatives analysis and decision making. CONCLUSIONS: The consequences of intangibility can be overcome by mechanisms that enable a common perspective among the participants involved in the productive process, and by the team members' familiarity with each other. PMID- 26545034 TI - Living with students: Lessons learned while pursuing tenure, administration, and raising a family. AB - An emerging promising practice in many universities has been the development of faculty-in-residence programs, in which university faculty members and their family moved into university student residences, sharing common living spaces with students. This case study is centered on two faculty-in-residence living in university residence halls. One was an assistant professor pursuing tenure while raising a young child, while the second was a tenured full professor and associate dean raising two teens. This case study offers the post-experience conclusions of these two faculty-in-residence individuals, noting the benefits and challenges each experienced while living -and working closely with these students outside of the university classroom, all while striving for an optimal balance in managing professional and familial obligations. PMID- 26545035 TI - Faculty-Mentor-in-Rez: The development of a new faculty-in-residence model. AB - Faculty-in-residence programs have long been touted as a successful way to provide for both intentional and casual out-of-the-classroom interactions between students and faculty. Despite research on the benefits to students and to faculty of such programs, academic commitments and lack of clarity around the role of live-in faculty has made recruiting of faculty a challenge. This case study provides an account of how McGill University, a publicly-funded, research intensive university in Montreal, Canada, undertook the development and implementation of a new faculty-in-residence model that honored the long history of faculty living in McGill's residences, provided structured opportunities for faculty-student engagement, and reflected McGill's unique residence culture. PMID- 26545036 TI - Urethral diverticulum in the female: a meta-analysis of modern series. AB - INTRODUCTION: Urethral diverticula are a complex problem for the female pelvic surgeon. Given the rarity of the condition most published series are small and single institutional. This is a review article and a meta-analysis including all case series of female urethral diverticulum from the year 2000 to 2015 including only those case series with a minimum of ten subjects. EVIDENCE ACQUISITION: Twenty-five articles were included and data was sufficient to perform a meta analysis on patient age, symptoms at presentation, physical exam findings, location of diverticulum, diverticular size, radiological findings, pathology, complications, and recurrence rates. EVIDENCE SYNTHESIS: Urethral diverticulum have variable symptom presentation and can mimic many other common conditions, but often present with a palpable urethral mass. Surgical diverticulectomy is the most commonly performed procedure, but does put the patient at risk for de novo stress incontinence and recurrent diverticula are not rare. Patients with pre existing stress incontinence can be safely offered concomitant autologous pubovaginal sling at the time of diverticulectomy. CONCLUSIONS: Pathology is benign 97% of the time but one must have a high degree of suspicion in the case of a firm mass or if MRI indicates a mass within the diverticula. Physicians need to have a high degree of suspicion particularly in those patients whose symptoms do not resolve with standard treatment and pelvic MRI is the investigation of choice. PMID- 26545037 TI - Ligand Replacement Approach to Raman-Responded Molecularly Imprinted Monolayer for Rapid Determination of Penicilloic Acid in Penicillin. AB - Penicilloic acid (PA) is a degraded byproduct of penicillin and often causes fatal allergies to humans, but its rapid detection in penicillin drugs remains a challenge due to its similarity to the mother structure of penicillin. Here, we reported a ligand-replaced molecularly imprinted monolayer strategy on a surface enhanced Raman scattering (SERS) substrate for the specific recognition and rapid detection of Raman-inactive PA in penicillin. The bis(phenylenediamine)-Cu(2+)-PA complex was first synthesized and stabilized onto the surface of silver nanoparticle film that was fabricated by a bromide ion-added silver mirror reaction. A molecularly imprinted monolayer was formed by the further modification of alkanethiol around the stabilized complex on the Ag film substrate, and the imprinted recognition site was then created by the replacement of the complex template with Raman-active probe molecule p-aminothiophenol. When PA rebound into the imprinted site in the alkanethiol monolayer, the SERS signal of p-aminothiophenol exhibited remarkable enhancement with a detection limit of 0.10 nM. The imprinted monolayer can efficiently exclude the interference of penicillin and thus provides a selective determination of 0.100/00 (w/w) PA in penicillin, which is about 1 order of magnitude lower than the prescribed residual amount of 1.00/00. The strategy reported here is simple, rapid and inexpensive compared to the traditional chromatography-based methods. PMID- 26545038 TI - New and Future Directions in Integrative Medicine Research Methods with a Focus on Aging Populations: A Review. AB - This review discusses existing and developing state-of-the-art noninvasive methods for quantifying the effects of integrative medicine (IM) in aging populations. The medical conditions of elderly patients are often more complex than those of younger adults, making the multifaceted approach of IM particularly suitable for aging populations. However, because IM interventions are multidimensional, it has been difficult to examine their effectiveness and mechanisms of action. Optimal assessment of IM intervention effects in the elderly should include a multifaceted approach, utilizing advanced analytic methods to integrate psychological, behavioral, physiological, and biomolecular measures of a patient's response to IM treatment. Research is presented describing methods for collecting and analyzing psychological data; wearable unobtrusive devices for monitoring heart rate variability, activity and other behavioral responses in real time; immunochemical methods for noninvasive molecular biomarker analysis, and considerations and analytical approaches for the integration of these measures. The combination of methods and devices presented in this review will provide new approaches for evaluating the effects of IM interventions in real-life ambulatory settings of older adults, and will extend the concept of mobile health to the domains of IM and healthy aging. PMID- 26545039 TI - Nonspherical Deltahedra in Low-Energy Dicarbalane Structures Testing the Wade Mingos Rules: The Regular Icosahedron Is Not Favored for the 12-Vertex Dicarbalane. AB - Theoretical studies on the dicarbalanes C2Al(n-2)Men (n = 7-14; Me = methyl) predict both carbon atoms to be located at degree 4 vertices of a central C2Al(n 2) deltahedron in the lowest energy structures. As a consequence, deltahedra having two degree 4 vertices, two degree 6 vertices, and eight degree 5 vertices rather than the regular icosahedron having exclusively degree 5 vertices are found for the 12-vertex dicarbalane C2Al10Me12. However, the lowest energy C2Al(n 2)Men (n = 7-11) structures are based on the same most spherical (closo) deltahedra as the corresponding deltahedral boranes. The lowest energy structures for the 13- and 14-vertex systems C2Al(n-2)Men (n = 13 and 14) are also deltahedra having exactly two degree 4 vertices for the carbon atoms. The six vertex C2Al4Me6 system is exceptional since bicapped tetrahedral and capped square pyramidal structures with degree 3 vertices for the carbon atoms are energetically preferred over the octahedral structure suggested by the Wade Mingos rules. PMID- 26545040 TI - Acid-Activatable Michael-Type Fluorescent Probes for Thiols and for Labeling Lysosomes in Live Cells. AB - A Michael addition is usually taken as a base-catalyzed reaction. Most fluorescent probes have been designed to detect thiols in slightly alkaline solutions (pH 7-9). The sensing reactions of almost all Michael-type fluorescent probes for thiols are faster in a high pH solution than in a low pH solution. In this work, we synthesized a series of 7-substituted 2-(quinolin-2 ylmethylene)malonic acids (QMAs, substituents: NEt2, OH, H, Cl, or NO2) and their ethyl esters (QMEs) as Michael-type fluorescent probes for thiols. The sensing reactions of QMAs and QMEs occur in distinct pH ranges, pH < 7 for QMAs and pH > 7 for QMEs. On the basis of experimental and theoretic studies, we have clarified the distinct pH effects on the sensing reactivity between QMAs and QMEs and demonstrated that two QMAs (NEt2, OH) are highly sensitive and selective fluorescent probes for thiols in acidic solutions (pH < 7) and promising dyes that can label lysosomes in live cells. PMID- 26545041 TI - Monohydroxylated Polybrominated Diphenyl Ethers (OH-PBDEs) and Dihydroxylated Polybrominated Biphenyls (Di-OH-PBBs): Novel Photoproducts of 2,6-Dibromophenol. AB - Hydroxylated polybromodiphenyl ethers (OH-PBDEs) are emerging aquatic pollutants, but their origins in the environment are not fully understood. There is evidence that OH-PBDEs are formed from bromophenols, but the underlying transformation processes remain unknown. Here, we investigate if the photoformation of OH-PBDEs from 2,6-dibromophenol in aqueous solution involves 2,6-bromophenoxyl radicals. After the UV irradiation of an aqueous 2,6-dibromophenol solution, HPLC-LTQ Orbitrap MS and GC-MS analysis revealed the formation of a OH-PBDE and a dihydroxylated polybrominated biphenyl (di-OH-PBB). Both dimeric photoproducts were tentatively identified as 4'-OH-BDE73 and 4,4'-di-OH-PBB80. In addition, three debromination products (4-OH-BDE34, 4'-OH-BDE27, and 4,4'-di-OH-PBBs) were observed. Electron paramagnetic resonance spectroscopy revealed the presence of a 2,6-dibromophenoxyl radical with a six-line spectrum (a(H) (2 meta) = 3.45 G, a(H) (1 para) = 1.04 G, g = 2.0046) during irradiation of a 2,6-dibromophenol solution in water. The 2,6-dibromophenoxyl radical had a relatively long half life (122 +/- 5 MUs) according to laser flash photolysis experiments. The para para C-C and O-para-C couplings of these 2,6-dibromophenoxyl radicals are consistent with the observed formation of both dimeric OH-PBDE and di-OH-PBB photoproducts. These findings show that bromophenoxyl radical-mediated phototransformation of bromophenols is a source of OH-PBDEs and di-OH-PBBs in aqueous environments that requires further attention. PMID- 26545042 TI - Effect of Water Content in N-Methylmorpholine N-Oxide/Cellulose Solutions on Thermodynamics, Structure, and Hydrogen Bonding. AB - Native crystalline cellulose is notoriously difficult to dissolve due to its dense hydrogen bond network between chains and weaker hydrophobic forces between cellulose sheets. N-Methylmorpholine N-oxide (NMMO), the solvent behind the Lyocell process, is one of the most successful commercial solvents for the nonderivatized dissolution of cellulose. In this process, water plays a very important role. Its presence at low concentrations allows NMMO to dissolve substantial amounts of cellulose, while at much higher concentrations it precipitates the crystalline fibers. Using all-atom molecular dynamics, we study the thermodynamic and structural properties of ternary solutions of cellulose, NMMO, and water. Using the two-phase thermodynamic method to calculate solvent entropy, we estimate the free energy of dissolution of cellulose as a function of the water concentration and find a transition of spontaneity that is in excellent agreement with experiment. In pure water, we find that cellulose dissolution is nonspontaneous, a result that is due entirely to strong decreases in water entropy. Although the combined effect of enthalpy on dissolution in water is negligible, we observe a net loss of hydrogen bonds, resulting in a change in hydrogen bond energy that opposes dissolution. At lower water concentrations, cellulose dissolution is spontaneous and largely driven by decreases in enthalpy, with solvent entropy playing only a very minor role. When searching for the root causes of this enthalpy decrease, a complex picture emerges in which not one but many different factors contribute to NMMO's good solvent behavior. The reduction in enthalpy is led by the formation of strong hydrogen bonds between cellulose and NMMO's N-oxide, intensified through van der Waals interactions between NMMO's nonpolar body and the nonpolar surfaces of cellulose and unhindered by water at low concentrations due to the formation of efficient hydrogen bonds between water and cellulose. PMID- 26545043 TI - A Circle Has No End: Role of Cyclic Topology and Accompanying Structural Reorganization on the Hole Distribution in Cyclic and Linear Poly-p-phenylene Molecular Wires. AB - pi-Conjugated organic oligomers/polymers hold great promise as long-range charge transfer materials for modern photovoltaic applications. However, a set of criteria for the rational design of functional materials is not yet available, in part because of a lack of understanding of charge distribution in extended pi conjugated systems of different topologies, and concomitant effects on redox and optical properties. Herein we demonstrate the role of cyclic versus linear topology in controlling the redox/optical properties and hole distribution in poly-p-phenylenes (PPs) with the aid of experiment, computation, and our recently developed multistate parabolic model (MPM). It is unequivocally shown that the hole distribution in both cyclic and linear poly-p-phenylene (n >= 7) cation radicals is limited to seven p-phenylene units, despite the very different topologies. However, the effect of topology is evidenced in the very different trends in oxidation potentials of cyclic versus linear PPs, which are shown to originate largely from the geometrical distortion of individual p-phenylene units in cyclic PPs. The presence of additional pairwise electronic coupling element in cyclic PPs, absent in linear PPs, plays a significant role only in smaller cyclic PP5 and PP6. This study provides a detailed conceptual description of cyclic and linear poly-p-phenylene cation radicals and demonstrates the versatility and predictive power of MPM, an important new tool for the design and synthesis of novel and efficient charge-transfer materials for molecular electronics and photovoltaic applications, an area of widespread interest. PMID- 26545044 TI - Periodontitis Awareness Amongst the General Public: A Critical Systematic Review to Identify Gaps of Knowledge. AB - BACKGROUND: Poor awareness of periodontal diseases and their consequences has been reported as the most frequent reason for periodontal treatment failure on a community basis. This study aims to identify the most relevant gaps of knowledge about periodontal diseases among the general public and to disclose whether these gaps are culturally consistent. METHODS: Systematic searches were conducted of the EMBASE, PubMed, and SciELO databases (1998 to November 2014). The search strategy was "periodontitis OR periodontal disease" and "knowledge OR awareness" as keywords and free text. Papers were included if they reported on community based, quantitative studies undertaken on adult individuals. RESULTS: A total of 2,330 references were identified (1,567 single papers), and six papers were finally selected. Raw data were grouped into nine dimensions of periodontal knowledge: 1) awareness; 2) etiology; 3) associated risks; 4) signs and symptoms; 5) risk factors; 6) treatment; 7) general knowledge; 8) prevention; and 9) attitudes. This classification recognized disease awareness (80%), etiology (75%), and periodontal-related risks (71.43%) as the most important knowledge deficits among the general public. These findings were confirmed by weighted data analysis. CONCLUSIONS: The number of available community-based investigations on periodontal knowledge is scarce and restricted to areas with a very high level of human development. Gaps of knowledge exist in every geographic area, with the most relevant issues of low awareness and poor knowledge about the etiology of periodontal diseases and their relation with systemic disorders. These results highlight the need for local, community-based investigations about periodontal knowledge and barriers hampering early diagnosis, as well as for adequate educational interventions focused on these issues. PMID- 26545045 TI - Interstitial lithium diffusion pathways in gamma-LiAlO2: a computational study. AB - Although the Li diffusion in single crystalline gamma-LiAlO2 was studied with temperature-dependent Li-7 NMR spectroscopy and conductivity measurements recently, the exact diffusion pathways are not yet clearly identified. Therefore, the present study aims at elucidating the diffusion pathways in gamma-LiAlO2 theoretically from first principles. Competing pathways for Li diffusion are investigated using the climbing-image nudged-elastic-band approach with periodic quantum-chemical density functional theory (DFT) method. Li can migrate between two regular LiO4 tetrahedral sites via Li point defect (VLi) and via a Li Frenkel defect (VLi + Lii). On the basis of calculated activation energies for Li diffusion pathways, it is concluded that Li conductivity is strongly dependent on the distribution of Li vacancies and interstitial Li in the lattice. For Frenkel defects where Lii is far away from the migrating Li atom, the calculated activation energies for jumps to nearest-neighbor vacant sites agree with experimental values. PMID- 26545046 TI - Comparative evaluation of mandibular canal visibility on cross-sectional cone beam CT images: a retrospective study. AB - OBJECTIVES: The purpose of this study was to determine the visibility of the mandibular canal (MC) in CBCT images and if the visibility of the MC is affected by gender, location and/or age. METHODS: CBCT images were evaluated for the visibility of the MC by a board-certified oral and maxillofacial radiologist, a board-certified periodontist and a periodontics resident. Representative slices were examined for the first premolar (PM(1)), second premolar (PM(2)), first molar (M(1)) and second molar (M(2)) sites by all examiners. The visibility of the MC was registered as either present or absent. RESULTS: 360 total CBCT cross sectional images were examined, with the MC identified in 204 sites (56%). Age had a significant effect on MC visibility, but it differed by location: for PM(1), age 47-56 had lower visibility than age 65+ (p = 0.0377). Gender also had a significant effect on canal visibility, where females had lower visibility than males overall (p = 0.0178) and had the most pronounced difference for PM(1) (p = 0.0054). Location had a significant effect on visibility, but it differed by age and by gender: for age 65+, M(2) had lower visibility than PM(1) (p = 0.0411) and PM(2) (p = 0.0180), while for females, PM(1) had lower visibility than M(1) (p = 0.0123) and M(2) (p = 0.0419). CONCLUSIONS: The MC was visualized only in just over half of the CBCT images. Age, gender and location had significant effects on the visibility. PMID- 26545047 TI - Salmonellosis Hospitalizations in the United States: Associated Chronic Conditions, Costs, and Hospital Outcomes, 2011, Trends 2000-2011. AB - Hospitalized salmonellosis patients with concurrent chronic conditions may be at increased risk for adverse outcomes, increasing the costs associated with hospitalization. Identifying important modifiable risk factors for this predominantly foodborne illness may assist hospitals, physicians, and public health authorities to improve management of these patients. The objectives of this study were to (1) quantify the burden of salmonellosis hospitalizations in the United States, (2) describe hospitalization characteristics among salmonellosis patients with concurrent chronic conditions, and (3) examine the relationships between salmonellosis and comorbidities by four hospital-related outcomes. A retrospective analysis of salmonellosis discharges was conducted using the Agency for Healthcare Research and Quality's Nationwide Inpatient Sample for 2011. A supplemental trend analysis was performed for the period 2000 2011. Hospitalization characteristics were examined using multivariable regression modeling, with a focus on four outcome measures: in-hospital death, total amount billed by hospitals for services, length of stay, and disease severity. In 2011, there were 11,032 total salmonellosis diagnoses; 7496 were listed as the primary diagnosis, with 86 deaths (case-fatality rate = 1.2%). Multivariable regression analyses revealed a greater number of chronic conditions (>=4) among salmonellosis patients was associated with higher mean total amount billed by hospitals for services, longer length of stay, and greater disease severity (p <= 0.05). From 2000 to 2011, hospital discharges for salmonellosis increased by 27.2%, and the mean total amount billed by hospitals increased nearly threefold: $9,777 (2000) to $29,690 (2011). Observed increases in hospitalizations indicate the burden of salmonellosis remains substantial in the United States. The positive association between increased number of chronic conditions and the four hospital-related outcomes affirms the need for continual healthcare and public health investments to prevent and control this disease in vulnerable groups. PMID- 26545051 TI - Family Medicine Student Interest. PMID- 26545049 TI - Microdeletion del(22)(q12.1) excluding the MN1 gene in a patient with craniofacial anomalies. AB - Several studies have recently reported that 22q12.1 deletions encompassing the MN1 gene are associated with craniofacial anomalies. These observations are consistent with the hypothesis that MN1 haploinsufficiency may be solely responsible for craniofacial anomalies and/or cleft palate. We report here the case of a 4-year-old boy presenting with global developmental delay and craniofacial anomalies including severe maxillary protrusion and retromicrognathia. Array-CGH detected a 2.4 Mb de novo deletion of chromosome 22q12.1 which did not encompass the MN1 gene thought to be the main pathological candidate in 22q12.1 deletions. This observation, combined with data from other patients from the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensemble Resources (DECIPHER), suggests that other gene(s) in the 22q12.1 region are likely involved in craniofacial anomalies and/or may contribute to the phenotypic variability observed in patients with MN1 deletion. PMID- 26545048 TI - Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. AB - Oligodendroglioma is the quintessential molecularly-defined brain tumor. The characteristic whole-arm loss of the long arm of chromosome 1 and the short arm of chromosome 19 (1p/19q-codeletion) within the genome of these tumors facilitated the reproducible molecular identification of this subcategory of gliomas. More recently, recurrent molecular genetic alterations have been identified to occur concurrently with 1p/19q-codeletion, and definitively identify these tumors, including mutations in IDH1/2, CIC, FUBP1, and the TERT promoter, as well as the absence of ATRX and TP53 alterations. These findings provide a foundation for the consistent diagnosis of this tumor type, upon which a generation of clinical investigators have assembled a strong evidence base for the effective treatment of this disease with radiation and chemotherapy. PMID- 26545052 TI - Medical Student Participation in Family Medicine Department Extracurricular Experiences and Choosing to Become a Family Physician. AB - BACKGROUND AND OBJECTIVES: Many factors influence a medical student's decision to choose a family medicine career. The impact of participation in extracurricular programs sponsored by family medicine departments is currently unclear. Medical student participation in four University of Washington Department of Family Medicine-sponsored programs (Community Health Advancement Program, Family Medicine Interest Group, Rural Underserved Opportunity Program, and the Underserved Pathway) could be associated with becoming a family physician. METHODS: Demographic data, results from a matriculation career interest survey, records indicating participation in the four extracurricular programs, and Match lists showing the specialty of each graduate were linked. Based on responses to the matriculation survey, graduates were categorized into four levels of initial family medicine interest. Chi-square tests compared both demographic data with initial family medicine interest levels and initial family medicine interest levels with program participation. For residency-matched graduates, odds ratios of matching to family medicine versus other specialties for specific family medicine programs and number of programs were calculated, controlling for demographic variables and initial family medicine interest levels. RESULTS: Older age, female graduates, a rural upbringing, and high level of initial family medicine interest were independently and significantly associated with choosing family medicine. Participation in the Family Medicine Interest Group (OR 2.45) and the Underserved Pathway (OR 4.37) and two or more family medicine programs (OR 2.01--2.22) was significantly associated with entering family medicine. CONCLUSIONS: Certain demographic factors and high initial interest in family medicine is associated with entering the specialty. Some, but not all, family medicine department-sponsored extracurricular programs were associated with choosing family medicine. PMID- 26545053 TI - Gold Humanism Honor Society Election and Academic Outcomes: A 10-Institution Study. AB - BACKGROUND AND OBJECTIVES: This study examines relationships among election to the Gold Humanism Honor Society (GHHS) and election to Alpha Omega Alpha (AOA), class rank, and residency selection to determine if GHHS members are more likely to select primary care residencies than students not elected to GHHS membership. METHODS: We evaluated five graduating classes (2006--2010) at 10 medical schools (n=5,481 students). Residency selections were grouped into primary care (family medicine, internal medicine, pediatrics, OB-GYN), surgery (including surgical specialties), or E-ROAD and other (including lifestyle practices-emergency medicine, radiology, ophthalmology, anesthesiology, and dermatology plus all other specialties, eg, neurology, pathology). RESULTS: A higher proportion of GHHS members were attracted to primary care compared to non-GHHS members (54.3% versus 44.5%). Additional comparisons between GHHS and non-GHHS members demonstrated that 33.1% of GHHS members matched into E-ROAD and other residencies, while 40.9% of non-GHHS went into one of these specialties. Fewer GHHS members chose general surgery or a surgical sub-specialty (12.6% versus 14.6%). More GHHS members were elected into AOA (30.3% versus 14.0%). Further, a far greater proportion of dual AOA/GHHS members elect family medicine residency versus AOA members not elected to GHHS. In addition, GHHS members had slightly higher mean scores on USMLE Step 1 and 2 CK (Clinical Knowledge) and mean class rank. CONCLUSIONS: This study demonstrates that students elected into the GHHS as an aggregate group tend to be academically higher achieving when compared to their non-GHHS peers and gravitate to a higher degree toward primary care and specifically to family medicine. PMID- 26545054 TI - A Survey of Family Medicine Department Chairs About Faculty With Disabilities: A CERA Study. AB - BACKGROUND AND OBJECTIVES: Despite 21 million US adults having a disability, little is known about the types of disabilities among faculty in family medicine departments, accommodations used, or work limitations. METHODS: We surveyed family medicine department chairs electronically about the number, types of disabilities encountered, accommodations and associated costs, and attitudes toward family medicine faculty with disabilities. This 10-item survey was part of the Council of Academic Family Medicine Educational Research Alliance omnibus survey. Data were summarized using descriptive statistics. RESULTS: The survey response rate was 59% (88/148). Types of disabilities were reported for approximately 50 faculty members by 31 department chairs; only seven knew about the disability at hiring. The most common impairments were mobility, hearing, and mental health problems. Accommodations included adjusting schedules, additional time to meet tasks, and assistive technology. No additional costs were reported for accommodations by about one-third of respondents while costs were over $5,000 for approximately one-quarter. Most chairs reported that faculty performance was similar to peers without disabilities (42.2%) or adequate but not at the level of peers (40%); only one reported inadequate job performance. Faculty members with disabilities appeared to be accepted by peers, patients, learners, and staff, and only two faculty left their program because of the disability. CONCLUSIONS: Most chairs did not report experience with faculty members with disabilities. The disabilities encountered and accommodations were not unusual, but costs were sometimes high. While about half of chairs reported adequate or superior job performance for their faculty with disabilities, a sizeable minority judged such faculty to have poorer performance than peers despite reporting wide acceptance of faculty with disabilities by patients and colleagues. This study raises concerns about potential underreporting by faculty with disabilities and poorer perceived job performance despite wide acceptance and provision of accommodations, sometimes at high cost. PMID- 26545055 TI - Preparing the Next Generation of Family Physicians to Improve Population Health: A CERA Study. AB - BACKGROUND AND OBJECTIVES: Family medicine leaders cite population health as a key tenet in the strategic plan outlining family medicine's role in improving America's health. Yet little is known about current practice in training family physicians in this area. This study describes the current practice and teaching of community medicine and population health in family medicine residency programs to support the broader goal of preparing the next generation of family physicians to deliver comprehensive primary care while improving population health. METHODS: Questions were added to the 2013 Council of Academic Family Medicine Educational Research Alliance (CERA) program directors (PD) survey detailing current teaching practices and identifying self-rated exemplary programs. Multivariate logistic regression models were built to predict program strength. RESULTS: A quarter of responding PDs (n=56) self-rate the strength of their community medicine curriculum; they are more likely to: have a faculty champion, have strong public health partnerships, teach community-oriented primary care well, and tend to serve densely populated regions (>500K). PDs ranked "knowledge and use of community resources" (n=142, 63%) and "teamwork" (n=127, 57%) as areas of community medicine taught best and research/evaluation (n=120, 54%) and population health (n=105, 47%) as areas not taught well. Resident/faculty time are cited as barriers to curricular success (n=144, 64% and n=134, 60%). CONCLUSIONS: Family medicine is well poised to take leadership in the teaching and practice of population health. Yet improvements are still needed and may be supported by dedicated time for faculty/residents, development of faculty champions, and targeted training in rural and suburban areas. PMID- 26545056 TI - Reminder Cards Improve Physician Documentation of Obesity But Not Obesity Counseling. AB - BACKGROUND AND OBJECTIVES: Physicians frequently fail to document obesity and obesity-related counseling. We sought to determine whether attaching a physical reminder card to patient encounter forms would increase electronic medical record (EMR) assessment of and documentation of obesity and dietary counseling. METHODS: Reminder cards for obesity documentation were attached to encounter forms for patient encounters over a 2-week intervention period. For visits in the intervention period, the EMR was retrospectively reviewed for BMI, assessment of "obesity" or "morbid obesity" as an active problem, free-text dietary counseling within physician notes, and assessment of "dietary counseling" as an active problem. These data were compared to those collected through a retrospective chart review during a 2-week pre-intervention period. We also compared physician self-report of documentation via reminder cards with EMR documentation. RESULTS: We found significant improvement in the primary endpoint of assessment of "obesity" or "morbid obesity" as an active problem (42.5% versus 28%) compared to the pre-intervention period. There was no significant difference in the primary endpoints of free-text dietary counseling or assessment of "dietary counseling" as an active problem between the groups. Physician self-reporting of assessment of "obesity" or "morbid obesity" as an active problem (77.7% versus 42.5%), free text dietary counseling on obesity (69.1% versus 35.4%) and assessment of "dietary counseling" as an active problem (54.3% versus 25.2%) were all significantly higher than those reflected in EMR documentation. CONCLUSIONS: This study demonstrates that physical reminder cards are a successful means of increasing obesity documentation rates among providers but do not necessarily increase rates of obesity-related counseling or documentation of counseling. Our study suggests that even with such interventions, physicians are likely under documenting obesity and counseling compared to self-reported rates. PMID- 26545057 TI - Incorporating Osteopathic Curriculum Into a Family Medicine Residency. AB - BACKGROUND AND OBJECTIVES: Literature review reveals that doctors of osteopathic medicine (DO) physicians desire to maintain their osteopathic identity and enhance their osteopathic skills during residency training. An effective osteopathic curriculum has enhanced the University of Missouri-Kansas City (UMKC) Family Medicine Residency Program's recruitment of strong osteopathic residency candidates. UMKC has been a dually accredited family medicine residency since 2006. The study sought to determine resident attitudes toward osteopathic identity and principles and the perceived effectiveness of our osteopathic curriculum. METHODS: An anonymous survey was sent to osteopathic residents and recent graduates still working within the Truman Medical Center (TMC) system. The survey questions assessed the perceived importance of osteopathic principles and the perceived effectiveness of the residency program's current osteopathic curriculum. RESULTS: The response rate of DO physicians representing seven colleges of osteopathic medicine (COM) was 29/30 (97%). Respondents agreed that the American Osteopathic Association (AOA) program is one of the strengths of our family medicine residency program. Respondents planned to utilize osteopathic manipulative therapy (OMT) in their own practice. Osteopathic principles stratified in order of importance were: OMT benefits our patients, maintaining hands-on OMT skills, and learning to integrate OMT into your office treatment regimen. CONCLUSIONS: Our residents value integrating OMT into their practices as a benefit to their patients, to maintain osteopathic skills, and to learn to integrate OMT into their office treatment regimen. They generally agreed that the AOA accredited program is one of the strengths of our residency program. They intend to utilize OMT when they are in practice. PMID- 26545058 TI - Health Policy and Advocacy for New Mexico Medical Students in the Family Medicine Clerkship. AB - BACKGROUND AND OBJECTIVES: Learners in medical education are often inadequately prepared to address the underlying social determinants of health and disease. The objective of this article is to describe the development, implementation, and evaluation of a Health Policy and Advocacy curriculum incorporated into our family medicine clerkship. METHODS: We developed a Health Policy and Advocacy course for medical students within our family medicine clerkship. We evaluated the curriculum using a survey of our own design administered to students before and after their clerkship year. We created a mean score for each subscale that measured (1) physician's role, (2) knowledge, and (3) confidence in ability and calculated differences between the pre-survey and the post-survey scores for four medical school classes. We also conducted a focus group to get student input on the new curriculum. RESULTS: Mean scores on the pre- and post-surveys were highest for the subscale regarding attitudes about a physician's role in health policy and advocacy and did not change over time. Scores for self-reported knowledge and confidence in abilities increased significantly from the beginning to the end of the clerkship year. Students were generally positive about the curriculum but had some concerns about finding time for advocacy in their future practices. CONCLUSIONS: Training in health care policy and advocacy can be successfully implemented into a medical school curriculum with positive outcomes in students' self-reported knowledge and confidence in their abilities. Work remains on providing advocacy role models for students. PMID- 26545059 TI - Service-Based Learning for Residents: A Success for Communities and Medical Education. AB - BACKGROUND AND OBJECTIVES: Community-based service-learning opportunities could support residents' acquisition of Accreditation Council for Graduate Medical Education (ACGME) competencies, but this concept has not been tested, and such programs are difficult to find. The objective of this work was to assess the value and the ACGME competency relevance of a service-learning program for residents that could be easily replicated nationally. METHODS: Forty-one family medicine residents from three training programs participated in the Stanford Youth Diabetes Coaches Program at six high schools in California and Georgia serving minority students of low socioeconomic status. Residents completed online surveys to provide qualitative feedback and assess the program's impact on their acquisition of residency program competencies and self-management support proficiencies, including prior use and planned use of action plans-a key self management support strategy. RESULTS: Ninety-five percent of residents indicated that the program was a valuable experience that contributed to acquisition of residency program competencies, including interpersonal and communication skills and communication with teens. Compared with baseline, significantly more residents reported intention to use action plans with patients following participation. Themes from qualitative feedback included: valuing the overall experience, increasing opportunities to practice teaching, enhancing their ability to communicate with adolescents, contributing to the health of the community, recognizing the potential of action plans, and increasing intent to use action plans. CONCLUSIONS: This pilot demonstrated that a brief service learning program can enhance standard residency curriculum by encouraging acquisition of ACGME competencies and promoting utilization of self-management support in clinical practice. PMID- 26545060 TI - Using Telemedicine Technology to Assess Physician Outpatient Teaching. AB - BACKGROUND AND OBJECTIVES: Video conferencing technology (telemedicine) can be applied to many settings within the medical community; we assessed the feasibility of its use in conducting observations of faculty at remote family medicine teaching sites. METHODS: We deployed seven telemedicine units to five family medicine residency sites and two observation stations within our division. Practice managers and physician faculty members received on-site training on the basic functionality of the technology, as well as "best practices" and minor troubleshooting techniques. Quick reference guides and other support documents were developed and provided for each site. During the remote faculty observation, two observers simultaneously viewed the resident being precepted, assessing the faculty member using a standardized tool. After the experience, all participants were asked to complete a survey on the usability of the technology. RESULTS: Nineteen observations were successfully conducted from November 2011 to December 2012. From a qualitative perspective, faculty accepted this as a viable means of faculty development. Minor technical hurdles were captured in the survey and improved upon as staff and faculty became more comfortable with the technology and as our technical capabilities allowed. Overall, the technology was rapidly accepted into the practices. CONCLUSIONS: Video teleconferencing represents a valuable tool that contributes to the development of faculty by making observation available to numerous sites, including remote areas that may have been previously challenging to reach due to logistics. Recent improvements in technology should make the process easier and allow more aspects of the encounters to be readily observed. PMID- 26545061 TI - Borderlands. PMID- 26545062 TI - A Team Reacts to a Patient's Death. PMID- 26545065 TI - To Be Well, or Not to Be Well, That Is the Question: What Will We Choose? PMID- 26545066 TI - Diversity of the Heart and Mind. PMID- 26545067 TI - Oropharyngeal oxygen and volatile anesthetic agent concentration during the use of laryngeal mask airway in children. AB - BACKGROUND: The laryngeal mask airway is increasingly used as an airway adjunct during general anesthesia. Although placement is generally simpler than an endotracheal tube, complete sealing of the airway may not occur, resulting in contamination of the oropharynx with anesthetic gases. Oropharyngeal oxygen enrichment may be one of the contributing factors predisposing to an airway fire during adenotonsillectomy. The current study prospectively assesses the oropharyngeal oxygen and volatile anesthetic agent concentration during laryngeal mask airway use in infants and children. METHODS: Following the induction of general anesthesia and placement of a laryngeal mask airway, the oropharyngeal gas sample was obtained by placing a 14-gauge catheter attached to the gas sampling tube into the oropharynx above the laryngeal mask airway. The oropharyngeal concentration of the oxygen and the anesthetic agent were recorded for five breaths during both spontaneous ventilation (SV) and positive pressure ventilation (PPV). RESULTS: The study included 238 patients. The oropharyngeal concentration of sevoflurane was >50% of the inspired sevoflurane concentration during SV in 10 of 238 (4.2%) patients and during PPV in 135 of 238 (56.7%) patients. Similarly, during SV and PPV, the oropharyngeal oxygen concentration was >21% in 30 of 238 (12.6%) patients and in 188 of 238 (79%) patients, respectively. Significantly, we also noticed that the oropharyngeal oxygen concentration exceeded 50% in 5 of 238 (2.1%) patients during SV and in 139 of 238 patients (58.4%) patients during PPV. CONCLUSIONS: With the use of a laryngeal mask airway and the administration of 100% oxygen, there was significant contamination of the oropharynx during both PPV and SV. The oropharyngeal concentration of oxygen was high enough to support combustion in a significant number of patients. The use of a laryngeal mask airway does not ensure sealing of the airway and may be one risk factor for an airway fire during adenotonsillectomy. PMID- 26545068 TI - Previsualizing a post-combustion world. PMID- 26545069 TI - Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. AB - BACKGROUND: Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Periodontal disease is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease. This review updates the previous version published in 2010. OBJECTIVES: The objective is to investigate the effect of periodontal therapy on glycaemic control in people with diabetes mellitus. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 31 December 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 31 December 2014), EMBASE via OVID (1980 to 31 December 2014), LILACS via BIREME (1982 to 31 December 2014), and CINAHL via EBSCO (1937 to 31 December 2014). ZETOC (1993 to 31 December 2014) and Web of Knowledge (1990 to 31 December 2014) were searched for conference proceedings. Additionally, two periodontology journals were handsearched for completeness, Annals of Periodontology (1996 to 2003) and Periodontology 2000 (1993 to 2003). We searched the US National Institutes of Health Trials Registry (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 DM (T1DM/T2DM) with a diagnosis of periodontitis. Interventions included periodontal treatments such as mechanical debridement, surgical treatment and antimicrobial therapy. Two broad comparisons were proposed:1. periodontal therapy versus no active intervention/usual care;2. periodontal therapy versus alternative periodontal therapy. DATA COLLECTION AND ANALYSIS: For this review update, at least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials and assessed included trials for risk of bias.Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c).Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing (BOP), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and probing pocket depth (PPD)), cost implications and diabetic complications. MAIN RESULTS: We included 35 studies (including seven from the previous version of the review), which included 2565 participants in total. All studies used a parallel RCT design, and 33 studies (94%) only targeted T2DM patients. There was variation between studies with regards to included age groups (ages 18 to 80), duration of follow-up (3 to 12 months), use of antidiabetic therapy, and included participants' baseline HbA1c levels (from 5.5% to 13.1%).We assessed 29 studies (83%) as being at high risk of bias, two studies (6%) as being at low risk of bias, and four studies (11%) as unclear. Thirty-four of the studies provided data suitable for analysis under one or both of the two comparisons.Comparison 1: low quality evidence from 14 studies (1499 participants) comparing periodontal therapy with no active intervention/usual care demonstrated that mean HbA1c was 0.29% lower (95% confidence interval (CI) 0.48% to 0.10% lower) 3 to 4 months post-treatment, and 0.02% lower after 6 months (five studies, 826 participants; 95% CI 0.20% lower to 0.16% higher).Comparison 2: 21 studies (920 participants) compared different periodontal therapies with each other. There was only very low quality evidence for the multiple head-to-head comparisons, the majority of which were unsuitable to be pooled, and provided no clear evidence of a benefit for one periodontal intervention over another. We were able to pool the specific comparison between scaling and root planing (SRP) plus antimicrobial versus SRP and there was no consistent evidence that the addition of antimicrobials to SRP was of any benefit to delivering SRP alone (mean HbA1c 0.00% lower: 12 studies, 450 participants; 95% CI 0.22% lower to 0.22% higher) at 3-4 months post-treatment, or after 6 months (mean HbA1c 0.04% lower: five studies, 206 patients; 95% CI 0.41% lower to 0.32% higher).Less than half of the studies measured adverse effects. The evidence was insufficient to conclude whether any of the treatments were associated with harm. No other patient-reported outcomes (e.g. quality of life) were measured by the included studies, and neither were cost implications or diabetic complications.Studies showed varying degrees of success with regards to achieving periodontal health, with some showing high levels of residual inflammation following treatment. Statistically significant improvements were shown for all periodontal indices (BOP, CAL, GI, PI and PPD) at 3-4 and 6 months in comparison 1; however, this was less clear for individual comparisons within the broad category of comparison 2. AUTHORS' CONCLUSIONS: There is low quality evidence that the treatment of periodontal disease by SRP does improve glycaemic control in people with diabetes, with a mean percentage reduction in HbA1c of 0.29% at 3-4 months; however, there is insufficient evidence to demonstrate that this is maintained after 4 months.There was no evidence to support that one periodontal therapy was more effective than another in improving glycaemic control in people with diabetes mellitus.In clinical practice, ongoing professional periodontal treatment will be required to maintain clinical improvements beyond 6 months. Further research is required to determine whether adjunctive drug therapies should be used with periodontal treatment. Future RCTs should evaluate this, provide longer follow-up periods, and consider the inclusion of a third 'no treatment' control arm.Larger, well conducted and clearly reported studies are needed in order to understand the potential of periodontal treatment to improve glycaemic control among people with diabetes mellitus. In addition, it will be important in future studies that the intervention is effective in reducing periodontal inflammation and maintaining it at lowered levels throughout the period of observation. PMID- 26545070 TI - Meniere's disease. AB - INTRODUCTION: Meniere's disease causes feelings of fullness or pressure in the ear, hearing loss, tinnitus, and recurrent bouts of vertigo, and mainly affects people aged 30-60 years. Meniere's disease is at first progressive but fluctuating, and episodes can occur in clusters. Vertigo usually resolves eventually, but the hearing deteriorates and the tinnitus and pressure may persist regardless of treatment. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of combination treatment (betahistine plus thiazide diuretic) to prevent attacks and delay disease progression of Meniere's disease? What are the effects of intratympanic interventions to prevent attacks and delay disease progression of Meniere's disease? What are the effects of non-drug interventions to prevent attacks and delay disease progression of Meniere's disease? What are the effects of dietary interventions to prevent attacks and delay disease progression of Meniere's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 200 studies. After deduplication and removal of conference abstracts, 151 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 100 studies and the further review of 51 full publications. Of the 51 full articles evaluated, five systematic reviews and four RCTs were added at this update. We performed a GRADE evaluation for eight PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for seven interventions based on information about the effectiveness and safety of betahistine plus thiazide diuretic, caffeine restriction, intratympanic corticosteroids, intratympanic gentamicin, psychological support, salt restriction, and vestibular rehabilitation. PMID- 26545071 TI - 2015: The Year of DNA Repair. PMID- 26545072 TI - Fragile Nucleosomes Influence Pol II Promoter Function. AB - In this issue of Molecular Cell, Kubik et al. (2015) describe how the RSC chromatin remodeling complex collaborates with two DNA sequence motifs and sequence-specific general regulatory factors to assemble fragile nucleosomes at highly transcribed yeast Pol II promoters, and they distinguish these from promoters bearing stable nucleosomes. PMID- 26545073 TI - Prevent and Cure: RPA Cooperates with Mre11-Sae2 in DNA Secondary Structure Repair. AB - DNA inversion duplications are genome rearrangements observed in cancer. In this issue, Deng et al. (2015) demonstrate that in S. cerevisiae RPA and Mre11-Sae2 cooperate to prevent the formation of inversion duplications initiated at short DNA secondary structures. PMID- 26545074 TI - Human Gene Promoters Are Intrinsically Bidirectional. PMID- 26545075 TI - Perspectives on Unidirectional versus Divergent Transcription. PMID- 26545076 TI - Single-Stranded DNA Cleavage by Divergent CRISPR-Cas9 Enzymes. AB - Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9-guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family. PMID- 26545077 TI - Nucleosome Stability Distinguishes Two Different Promoter Types at All Protein Coding Genes in Yeast. AB - Previous studies indicate that eukaryotic promoters display a stereotypical chromatin landscape characterized by a well-positioned +1 nucleosome near the transcription start site and an upstream -1 nucleosome that together demarcate a nucleosome-free (or -depleted) region. Here we present evidence that there are two distinct types of promoters distinguished by the resistance of the -1 nucleosome to micrococcal nuclease digestion. These different architectures are characterized by two sequence motifs that are broadly deployed at one set of promoters where a nuclease-sensitive ("fragile") nucleosome forms, but concentrated in a narrower, nucleosome-free region at all other promoters. The RSC nucleosome remodeler acts through the motifs to establish stable +1 and -1 nucleosome positions, while binding of a small set of general regulatory (pioneer) factors at fragile nucleosome promoters plays a key role in their destabilization. We propose that the fragile nucleosome promoter architecture is adapted for regulation of highly expressed, growth-related genes. PMID- 26545078 TI - Structure of the RNA Helicase MLE Reveals the Molecular Mechanisms for Uridine Specificity and RNA-ATP Coupling. AB - The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the Drosophila dosage compensation complex. We identified a stable MLE core comprising the DExH helicase module and two auxiliary domains: a dsRBD and an OB like fold. MLEcore is an unusual DExH helicase that can unwind blunt-ended RNA duplexes and has specificity for uridine nucleotides. We determined the 2.1 A resolution structure of MLEcore bound to a U10 RNA and ADP-AlF4. The OB-like and dsRBD folds bind the DExH module and contribute to form the entrance of the helicase channel. Four uridine nucleotides engage in base-specific interactions, rationalizing the conservation of uridine-rich sequences in critical roX substrates. roX2 binding is orchestrated by MLE's auxiliary domains, which is prerequisite for MLE localization to the male X chromosome. The structure visualizes a transition-state mimic of the reaction and suggests how eukaryotic DEAH/RHA helicases couple ATP hydrolysis to RNA translocation. PMID- 26545080 TI - Micro-invasive interventions for managing proximal dental decay in primary and permanent teeth. AB - BACKGROUND: Proximal dental lesions, limited to dentine, are traditionally treated by invasive (drill and fill) means. Non-invasive alternatives (e.g. fluoride varnish, flossing) might avoid substance loss but their effectiveness depends on patients' adherence. Recently, micro-invasive approaches for treating proximal caries lesions have been tried. These interventions install a barrier either on top (sealing) or within (infiltrating) the lesion. Different methods and materials are currently available for micro-invasive treatments, such as sealing via resin sealants, (polyurethane) patches/tapes, glass ionomer cements (GIC) or resin infiltration. OBJECTIVES: To evaluate the effects of micro invasive treatments for managing proximal caries lesions in primary and permanent dentition in children and adults. SEARCH METHODS: We searched the following databases to 31 December 2014: the Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via OVID, EMBASE via OVID, LILACs via BIREME Virtual Health Library, Web of Science Conference Proceedings, ZETOC Conference Proceedings, Proquest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and the World Health Organization (WHO) International Clinical Trials Registry Platform. We searched the metaRegister of Controlled Trials to 1 October 2014. There were no language or date restrictions in the searches of the electronic databases. SELECTION CRITERIA: We included randomised controlled trials of at least six months' duration that compared micro invasive treatments for managing non-cavitated proximal dental decay in primary teeth, permanent teeth or both, versus non-invasive measures, invasive means, no intervention or placebo. We also included studies that compared different types of micro-invasive treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, extracted data and assessed the risk of bias. We used standard methodological procedures expected by Cochrane to evaluate risk of bias and synthesise data. We conducted meta-analyses with the random effects model, using the Becker-Balagtas method to calculate the odds ratio (OR) for lesion progression. We assessed the quality of the evidence using GRADE methods. MAIN RESULTS: We included eight trials, which randomised 365 participants. The trials all used a split-mouth design, some with more than one pair of lesions treated within the same participant. Studies took place in university or dental public health clinics in Brazil, Colombia, Denmark, Germany, Thailand, Greenland and Chile. Six studies evaluated the effects of micro invasive treatments in the permanent dentition and two studies on the primary dentition, with caries risk ranging from low to high. Investigators measured caries risk in different studies either by caries experience alone or by using the Cariogram programme, which combines eight contributing factors, including caries experience, diet, saliva and other factors related to caries. The follow up period in the trials ranged from one to three years. All studies used lesion progression as the primary outcome, evaluating it by different methods of reading radiographs. Four studies received industry support to carry out the research, with one of them being carried out by inventors of the intervention.We judged seven studies to be at high overall risk of bias, primarily due to lack of blinding of participants and personnel. We evaluated intervention effects for all micro-invasive therapies and analysed subgroups according to the different treatment methods reported in the included studies.Our meta-analysis, which pooled the most sensitive set of data (in terms of measurement method) from studies presenting data in a format suitable for meta-analysis, showed that micro invasive treatment significantly reduced the odds of lesion progression compared with non-invasive treatment (e.g fluoride varnish) or oral hygiene advice (e.g to floss) (OR 0.24, 95% CI 0.14 to 0.41; 602 lesions; seven studies; I(2) = 32%). There was no evidence of subgroup differences (P = 0.36).The four studies that measured adverse events reported no adverse events after micro-invasive treatment. Most studies did not report on any further outcomes.We assessed the quality of evidence for micro-invasive treatments as moderate. It remains unclear which micro-invasive treatment is more advantageous, or if certain clinical conditions or patient characteristics are better suited for micro-invasive treatments than others. AUTHORS' CONCLUSIONS: The available evidence shows that micro-invasive treatment of proximal caries lesions arrests non-cavitated enamel and initial dentinal lesions (limited to outer third of dentine, based on radiograph) and is significantly more effective than non-invasive professional treatment (e.g. fluoride varnish) or advice (e.g. to floss). We can be moderately confident that further research is unlikely to substantially change the estimate of effect. Due to the small number of studies, it does remain unclear which micro invasive technique offers the greatest benefit, or whether the effects of micro invasive treatment confer greater or lesser benefit according to different clinical or patient considerations. PMID- 26545079 TI - Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification. AB - Foldback priming at DNA double-stranded breaks is one mechanism proposed to initiate palindromic gene amplification, a common feature of cancer cells. Here, we show that small (5-9 bp) inverted repeats drive the formation of large palindromic duplications, the major class of chromosomal rearrangements recovered from yeast cells lacking Sae2 or the Mre11 nuclease. RPA dysfunction increased the frequency of palindromic duplications in Sae2 or Mre11 nuclease-deficient cells by ~ 1,000-fold, consistent with intra-strand annealing to create a hairpin capped chromosome that is subsequently replicated to form a dicentric isochromosome. The palindromic duplications were frequently associated with duplication of a second chromosome region bounded by a repeated sequence and a telomere, suggesting the dicentric chromosome breaks and repairs by recombination between dispersed repeats to acquire a telomere. We propose secondary structures within single-stranded DNA are potent instigators of genome instability, and RPA and Mre11-Sae2 play important roles in preventing their formation and propagation, respectively. PMID- 26545081 TI - Model for end-stage liver disease score in the first 3 weeks after liver transplantation as a predictor for long-term outcome. AB - BACKGROUND: Early allograft dysfunction after liver transplantation (LTX) is not well defined. The aim of this study was to evaluate the value of early post transplant model for end-stage liver disease (MELD) scores for predicting long term outcome after transplantation. METHODS: In this single-center retrospective study, 362 consecutive patients after LTX were included. MELD scores at 7, 14, and 21 postoperative days (PODs) were calculated from primary lab values. Receiver operating characteristic (ROC) analyses were carried out to determine the critical cutoff MELD scores for patient and graft survival. RESULTS: One year after transplantation, the patient and graft survival rates were 85 and 69%, respectively. Although pretransplant MELD scores were similar, they were significantly different at POD7, POD14, and POD21 between patients who died and those who survived the first year after transplantation. As shown by ROC curves, for patient survival, the optimal time point is POD14 with a cutoff MELD of 17. At this time point, patients with a MELD below 17 showed a 1-year survival rate of 94.3% and patients with a MELD of 17 and higher showed a 1-year survival rate of only 75.4%. For graft survival, the optimal time point was day 7 and a cutoff MELD of 29 (92% at MELD<29; 56.4% at MELD>=29). A multivariate analysis of potential risk factors indicated a significant role of serum bilirubin and MELD score determined on POD14 for patient survival. CONCLUSION: In conclusion, early postoperative MELD scores predict outcome after LTX. The postoperative MELD score at POD14 is a good predictor for patient survival and at POD7 for the graft survival after LTX. PMID- 26545082 TI - Hyperuricemia and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis. AB - BACKGROUND: Previous studies have suggested a possible association between hyperuricemia and nonalcoholic fatty liver disease (NAFLD), but the risk of NAFLD in individuals with hyperuricemia had not been fully quantified. A systematic review and meta-analysis of relevant studies was carried out to estimate the influence of hyperuricemia on the risk of NAFLD. METHODS: PubMed, Embase, Web of Science, and Wanfang databases were searched for cohort or cross-sectional studies assessing the association between hyperuricemia and NAFLD. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using a random-effects model to estimate the impact of hyperuricemia on the risk of NAFLD. RESULTS: Thirteen studies from 12 articles were finally included in the meta-analysis. There were a total of 117,712 participants and 28,446 (24.2%) NAFLD cases. Individuals with hyperuricemia had an obviously increased risk of NAFLD compared with those without hyperuricemia (RR=1.79, 95% CI 1.55-2.07, P<0.001). Increased risk of NAFLD was obviously associated with hyperuricemia in both men (RR=1.26, 95% CI 1.15-1.37, P<0.001) and women (RR=2.01, 95% CI 1.58-2.56, P<0.001). Subgroup analyses further identified the robustness of the association between hyperuricemia and NAFLD. CONCLUSION: Hyperuricemia is associated with an increased risk of NAFLD in Asian populations. Further prospective cohort studies are needed to assess the impact of hyperuricemia on the risk of NAFLD in Western countries. PMID- 26545083 TI - Atlanta, revised Atlanta, and Determinant-based classification--application in a cohort of Portuguese patients with acute pancreatitis. AB - BACKGROUND: Acute pancreatitis (AP) represents a complex and potentially fatal disease with a highly variable clinical course. Three classification systems for assessing the severity in AP have been validated for clinical use. AIMS: The aim of the present study was to evaluate the performance of the Atlanta and Determinant-based classifications in predicting severe clinical outcomes in patients with AP. METHODS: In this retrospective study we reviewed the treatment and follow-up records of 525 patients with AP admitted to our unit between the years of 2003 and 2014. Outcomes included mortality, admission to the ICU, need for interventional procedures or nutritional support, and duration of hospital and ICU stay. RESULTS: The prevalence of organ failure and persistent organ failure in our cohort was 23.0 and 10.7%, respectively, and the mortality rate was 5.9%. Higher grades of severity were associated with worse outcomes in all classification systems. The revised Atlanta and Determinant-based classifications performed similarly in predicting outcomes, and both proved to be superior to the former classic Atlanta classification. CONCLUSION: Recent classifications proved to be more accurate in predicting important clinical outcomes in patients with AP. PMID- 26545084 TI - Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D. AB - INTRODUCTION: Viral hepatitis B (VHB) represents a major public health problem. Studies from HIV multidrug patients have associated the use of tenofovir disoproxil fumarate (TDF) with renal dysfunction and phosphate wasting. OBJECTIVE: The aim of this study was to examine the effect of year-long TDF monotherapy on renal function in VHB patients. PATIENTS AND METHODS: We evaluated adult patients diagnosed with VHB before treatment initiation (T0), and after 3 and 12 months (T3 and T12) of TDF initiation. Estimated glomerular filtration rate (eGFR) was estimated by serum cystatin C and creatinine. In addition, urinary electrolytes and tubular biomarkers (cystatin C, beta2-microglobulin and neutrophil gelatinase-associated lipocalin) were analyzed, as well as parathyroid hormone (PTH) and 25(OH)vitamin D levels. RESULTS: After 1 year, 32 patients completed the study, 22 (68.7%) men and 12 (37.5%) Whites, mean age 44.1+/-12.0 years. We found that serum electrolytes were similar at baseline and 3 or 12 months after initiation of TDF monotherapy. In addition, urinary fractional excretions of electrolytes as well as proteinuria, albuminuria, urinary beta2 microglobulin, and urinary cystatin C showed no significant differences across the treatment timeline. There were also no statistical differences in the eGFR. There was a statistically significant increase in the PTH (Friedman's test, P=0.012), but the 25(OH)vitamin D levels were in the normal range in the beginning and did not change at the follow-up. Moreover, there was no correlation between the initial levels of vitamin D and the corresponding increases in the PTH values. CONCLUSION: If used as monotherapy in hepatitis B patients for a 12 month period, TDF is not associated with changes in either eGFR or a panel of urinary biomarkers. Serum and urinary electrolytes also remained unchanged. Of note, a significant increase in the PTH was found, although not related to the 25(OH)vitamin D initial status. PMID- 26545085 TI - Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. AB - BACKGROUND: Isotretinoin is a treatment option for severe nodulocystic acne. However, its use has inconsistently been associated with the development of inflammatory bowel disease (IBD). This meta-analysis aims to elucidate the association between isotretinoin exposure and the risk for IBD. METHODS: A comprehensive search of PubMed/MEDLINE, CINAHL, the Cochrane database, and Google Scholar was performed (July 2015). All studies on the development of IBD in patients with or without prior exposure to isotretinoin, along with control participants, were included. Meta-analysis was carried out using the Mantel Haenszel random effect model to assess the risk for IBD in the context of prior isotretinoin exposure. RESULTS: In a pooled analysis of six research studies, there was no increased risk of developing IBD in patients exposed to isotretinoin compared with patients not exposed to isotretinoin [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.82, 1.42, P=0.59]. Furthermore, there was no increased risk of developing Crohn's disease (OR 0.98, 95% CI 0.62, 1.55, P=0.93, I(2)=62%) or ulcerative colitis (OR 1.14, 95% CI 0.79, 1.63, P=0.49, I(2)=44%) in patients exposed to isotretinoin compared with those not exposed to the medication. CONCLUSION: Isotretinoin exposure is not associated with an increased risk of developing both ulcerative colitis and Crohn's disease. PMID- 26545086 TI - The cost-effectiveness of daclatasvir-based regimens for the treatment of hepatitis C virus genotypes 1 and 4 in the UK. AB - OBJECTIVE: This study aimed to determine the cost-effectiveness of daclatasvir in combination with other medicinal products for the treatment of patients with hepatitis C virus genotypes 1 and 4 and advanced liver disease in the UK. METHODS: A published and validated Markov model designed to simulate the natural history of chronic hepatitis C was used to compare daclatasvir with relevant treatment options for patients with hepatitis C virus genotypes 1 and 4 and a METAVIR score of F3-F4. Patients were defined according to their treatment status; that is, naive, experienced or interferon ineligible/intolerant. Data inputs for the analysis were derived from published sources, UK-specific where possible. A lifetime horizon was used, with costs and benefits discounted at 3.5%. RESULTS: Daclatasvir-based regimens are estimated to be cost-effective versus no treatment and established standard-of-care regimens, including telaprevir in combination with pegylated interferon-alpha+ribavirin (PR), boceprevir in combination with PR and PR alone (incremental cost-effectiveness ratio range: L3715-L15,408). The cost-effectiveness of daclatasvir-based regimens versus emerging regimens (sofosbuvir or simeprevir based) is less consistent, but was dominant or cost-effective (incremental cost-effectiveness ratio range: L1394 L28,393) in all except two scenarios. CONCLUSION: Daclatasvir-based regimens are expected to be highly cost-effective for the majority patients with advanced disease versus relevant comparator regimens, including newer direct-acting antiviral regimens. PMID- 26545087 TI - Facial hypersensitivity and trigeminal pathology in mice with experimental autoimmune encephalomyelitis. AB - Trigeminal neuropathic pain is a well-recognized complication of the demyelinating disease multiple sclerosis (MS). However, the mechanisms underlying MS-related trigeminal neuropathic pain are poorly understood. This can be attributed, at least in part, to the lack of an animal model that exhibits trigeminal pathology similar to that described in MS. Experimental autoimmune encephalomyelitis (EAE) is an animal model that is commonly used to study the pathophysiology of MS. We show here that mice with EAE exhibit increased sensitivity to air puffs applied to the whisker pad. The increased sensitivity to air puff stimulation is accompanied by T cell infiltration and glial activation at several points along the trigeminal primary afferent pathway. We also observe demyelination of the intra- and extra-pontine aspects of the trigeminal sensory root and the spinal trigeminal tract. This is the first study to show orofacial sensory disturbances and trigeminal demyelination in EAE. Collectively, our data suggest that EAE may be a useful model for understanding MS-related trigeminal neuropathic pain conditions such as trigeminal neuralgia. PMID- 26545088 TI - The alpha5 subunit containing GABAA receptors contribute to chronic pain. AB - It has been recently proposed that alpha5-subunit containing GABAA receptors (alpha5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of alpha5-GABAA receptors in the loss of GABAergic inhibition and in formalin-induced, complete Freund's adjuvant (CFA)-induced and L5 and L6 spinal nerve ligation-induced long lasting hypersensitivity. Formalin or CFA injection and L5 and L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression of the Hofmann reflex. Peripheral and intrathecal pretreatment or post-treatment with the alpha5-GABAA receptor antagonist, L-655,708 (0.15-15 nmol), prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased alpha5 GABAA receptor mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. The alpha5-GABAA receptors were localized in the dorsal spinal cord and DRG colabeling with NeuN, CGRP, and IB4 which suggests their presence in peptidergic and nonpeptidergic neurons. These receptors were found mainly in small and medium sized neurons. Formalin injection enhanced alpha5-GABAA receptor fluorescence intensity in spinal cord and DRG at 3 and 6 days. Intrathecal administration of L-655,708 (15 nmol) prevented and reversed formalin-induced impairment of rate-dependent depression. These results suggest that alpha5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long lasting secondary allodynia and hyperalgesia. PMID- 26545089 TI - Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury in Mouse Model. AB - OBJECTIVE: To investigate the protective role of the sonic hedgehog (SHH) signaling associated with a lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model. METHODS: Male BALB/c mice were randomly divided into four groups: control, LPS, LPS-cyclopamine group and cyclopamine group. ALI was induced by LPS ip injection (5 mg/kg). The sonic hedgehog inhibitor cyclopamine (50 mg/kg) was given to the LPS-cyclopamine group at 30 min after LPS injection as well as normal mice as control. Lung injury was observed histologically in hematoxylin and eosin (HE) stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D). mRNA expression levels of TNF-alpha, SHH, Patched (PTC) and GLI1 in lung tissue were studied with real time quantitative PCR (RT-PCR), while the protein expression of SHH and GLI1 was determined by western blot analysis. RESULTS: Lung tissue injury score, thickness of alveolar septa, W/D, and TNF-alpha mRNA expression levels were significantly higher in the ALI mice than the normal mice (P<0.05). The mRNA expression levels of SHH, PTC, and GLI1 in the ALI mice were significantly higher at 12h and 24h after LPS injection, but not at the 6h time point. Protein production of SHH and GLI1 at 6h, 12h, and 24h in the lungs of ALI mice significantly increased, in a time-dependent manner, compared with that in normal mice. Cyclopamine alone has no effect on pathological changes in normal mice. Intervention with cyclopamine in ALI mice led to a reduction in mRNA levels of SHH, PTC, and GLI1 as well as SHH and GLI1 protein levels; meanwhile, the pathological injury scores of lung tissues, thickness of alveolar septa, W/D, and mRNA expression levels of TNF-alpha increased compared with mice receiving LPS only. CONCLUSION: The SHH signaling pathway was activated in response to LPS-induced ALI, and up-regulation of SHH expression could alleviate lung injury and be involved in the repair of injured lung tissue. PMID- 26545091 TI - Drug updates and approvals: 2015 in review. AB - This article highlights important prescribing information for some drugs that received FDA approval within the past year. These include: atazanavir and cobicistat (Evotaz(r)), ceftazidime and avibactam (Avycaz(r)), edoxaban (Savaysa(r)), ivabradine (Corlanor(r)), liraglutide (rDNA origin) injection (Saxenda(r)), perindopril arginine and amlodipine besylate (Prestalia(r)), and secukinumab (Cosentyx(r)) subcutaneous injection. PMID- 26545092 TI - Red eye emergencies in primary care. AB - Severe red eye conditions can be the result of intraocular inflammation, corneal insults or inflammation, and acute glaucoma. These pathologies require the knowledge and assessment tools of an ophthalmologist. This article will discuss red eye emergencies that the NP should promptly recognize and refer to ophthalmology. PMID- 26545090 TI - Adaptation to High Ethanol Reveals Complex Evolutionary Pathways. AB - Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID- 26545093 TI - Identification of HOXD4 Mutations in Spinal Extradural Arachnoid Cyst. AB - Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater and leads to neurological disturbances. We previously showed that familial SEDAC is caused by FOXC2 mutation; however, the causal gene of sporadic SEDAC has not been identified. To identify the causal gene of sporadic SEDAC, we performed whole exome sequencing for 12 subjects with sporadic SEDAC and identified heterozygous HOXD4 loss-of-function mutations in three subjects. HOXD4 haplo-insufficiency causes SEDAC and a transcriptional network containing HOXD4 and FOXC2 is involved in the development of the dura mater and the etiology of SEDAC. PMID- 26545094 TI - Endobronchial Ultrasound Changed the World of Lung Cancer Patients: A 11-Year Institutional Experience. AB - OBJECTIVES: The role of advanced bronchoscopic diagnostic techniques in the detection and staging of lung cancer has increased sharply in recent years. The development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions (PLLs). We investigated the impact of using EBUS as a diagnostic method for tissue acquisition in lung cancer patients. METHODS: In a single center observational retrospective study, 3712 subjects were diagnosed with lung cancer from 2003 to 2013 (EBUS was introduced in 2008). Thus, we divided the data into two periods: the conventional bronchoscopy period (2003 to 2007) and the EBUS period (2008 to 2013). RESULTS: A total of 3712 patients were included in the analysis. Comparing the conventional bronchoscopy period with the EBUS period data, there has been a significant reduction in the use of diagnostic modalities: CT-guided biopsy (P < 0.0001) and pleural effusion cytology (P < 0.0001). The proportion of subjects diagnosed using bronchoscopy significantly increased from 39.4% in the conventional period to 47.4% in the EBUS period (P < 0.0001). In the EBUS period, there has also been a significant increase in the proportion of patients proceeding directly to diagnostic surgery (P < 0.0001). Compared to bronchoscopy, the incidence of complications was higher in those who underwent CT guide biopsy. The incidence of iatrogenic pneumothorax significantly decreased in the EBUS period. CONCLUSIONS: Advanced bronchoscopic techniques are widely used in the diagnosis of lung cancer. At our institution, the increasing use of EBUS for providing lung cancer diagnosis has led to a significant reduction in other diagnostic modalities, namely CT-guided biopsy and pleural effusion cytology. These changes in practice also led to a reduction in the incidence of complications. PMID- 26545095 TI - Mental Health Help-Seeking Intentions and Preferences of Rural Chinese Adults. AB - PURPOSE: We aimed to investigate mental health help-seeking intentions and preferences of rural Chinese adults and determine predictors of the intentions. METHODS: A total of 2052 representative rural residents aged 18-60 completed a cross-sectional survey by face-to-face interviews. The survey included seven questions asking about respondents' help-seeking intentions and preferences, and a series of internationally validated instruments to assess self-perceived health status, depression, anxiety, alcohol abuse, mental health literacy, and attitudes towards mental illness. RESULTS: Nearly 80% of respondents were willing to seek psychological help if needed, and 72.4% preferred to get help from medical organizations, yet only 12% knew of any hospitals or clinics providing such help. A multivariate analysis of help-seeking intention revealed that being female, having lower education, higher social health, higher mental health knowledge, and physical causal attribution for depression were positive predictors of help seeking intention. CONCLUSION: A huge gap exists between the relatively higher intention for help-seeking and significantly lower knowledge of helpful resources. Predictors of help-seeking intention for mental problems in the current study are consistent with previous studies. Interventions to increase help-seeking for mental problems by Chinese rural adults may be best served by focusing on increasing public awareness of help sources, as well as improving residents' mental health literacy and social health, with special focus on males and those more educated. PMID- 26545096 TI - Elevated Vibration Perception Thresholds in CIDP Patients Indicate More Severe Neuropathy and Lower Treatment Response Rates. AB - INTRODUCTION: Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy. OBJECTIVES: Explore the utility of VPT examination in CIDP patients. METHODS: CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted. RESULTS: 70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p<0.0001), lower sensory and motor amplitudes and reduced conduction velocities on nerve conduction studies, and lower treatment response rates (54% vs. 93%, p = 0.01). CONCLUSION: VPT examination is a simple tool, which is a reliable and sensitive measure not only for diabetic neuropathy, but also for CIDP. Moreover, in CIDP, elevated VPT values are also associated with lower treatment response rates. PMID- 26545097 TI - A GPU Simulation Tool for Training and Optimisation in 2D Digital X-Ray Imaging. AB - Conventional radiology is performed by means of digital detectors, with various types of technology and different performance in terms of efficiency and image quality. Following the arrival of a new digital detector in a radiology department, all the staff involved should adapt the procedure parameters to the properties of the detector, in order to achieve an optimal result in terms of correct diagnostic information and minimum radiation risks for the patient. The aim of this study was to develop and validate a software capable of simulating a digital X-ray imaging system, using graphics processing unit computing. All radiological image components were implemented in this application: an X-ray tube with primary beam, a virtual patient, noise, scatter radiation, a grid and a digital detector. Three different digital detectors (two digital radiography and a computed radiography systems) were implemented. In order to validate the software, we carried out a quantitative comparison of geometrical and anthropomorphic phantom simulated images with those acquired. In terms of average pixel values, the maximum differences were below 15%, while the noise values were in agreement with a maximum difference of 20%. The relative trends of contrast to noise ratio versus beam energy and intensity were well simulated. Total calculation times were below 3 seconds for clinical images with pixel size of actual dimensions less than 0.2 mm. The application proved to be efficient and realistic. Short calculation times and the accuracy of the results obtained make this software a useful tool for training operators and dose optimisation studies. PMID- 26545098 TI - Time-Dependent Increase in Network Response to Stimulation. AB - In vitro neuronal cultures have become a popular method with which to probe network-level neuronal dynamics and phenomena in controlled laboratory settings. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Here we demonstrate the effects of a high frequency electrical stimulation signal in training cultured networks of cortical neurons. Networks receiving this training signal displayed a time-dependent increase in the response to a low frequency probing stimulation, particularly in the time window of 20-50 ms after stimulation. This increase was found to be statistically significant as compared to control networks that did not receive training. The timing of this increase suggests potentiation of synaptic mechanisms. To further investigate this possibility, we leveraged the powerful Cox statistical connectivity method as previously investigated by our group. This method was used to identify and track changes in network connectivity strength. PMID- 26545099 TI - Network Plasticity as Bayesian Inference. AB - General results from statistical learning theory suggest to understand not only brain computations, but also brain plasticity as probabilistic inference. But a model for that has been missing. We propose that inherently stochastic features of synaptic plasticity and spine motility enable cortical networks of neurons to carry out probabilistic inference by sampling from a posterior distribution of network configurations. This model provides a viable alternative to existing models that propose convergence of parameters to maximum likelihood values. It explains how priors on weight distributions and connection probabilities can be merged optimally with learned experience, how cortical networks can generalize learned information so well to novel experiences, and how they can compensate continuously for unforeseen disturbances of the network. The resulting new theory of network plasticity explains from a functional perspective a number of experimental data on stochastic aspects of synaptic plasticity that previously appeared to be quite puzzling. PMID- 26545100 TI - Dihydroagarofuranoid Sesquiterpenes as Acetylcholinesterase Inhibitors from Celastraceae Plants: Maytenus disticha and Euonymus japonicus. AB - Natural cholinesterase inhibitors have been found in many biological sources. Nine compounds with agarofuran (epoxyeudesmane) skeletons were isolated from seeds and aerial parts of Maytenus disticha and Euonymus japonicus. The identification and structural elucidation of compounds were based on spectroscopic data analyses. All compounds had inhibitory acetylcholinesterase (AChE) activity. These natural compounds, which possessed mixed or uncompetitive mechanisms of inhibitory activity against AChE, may be considered as models for the design and development of new naturally occurring drugs for management strategies for neurodegenerative diseases. This is the first report of these chemical structures for seeds of M. disticha. PMID- 26545101 TI - Prolonged Operative Time to Extubation Is Not a Useful Metric for Comparing the Performance of Individual Anesthesia Providers. AB - BACKGROUND: One anesthesiologist performance metric is the incidence of "prolonged" (15 min or longer after dressing complete) times to extubation. The authors used several methods to identify the performance outliers and assess whether targeting these outliers for reduction could improve operating room workflow. METHODS: Time to extubation data were retrieved for 27,757 anesthetics and 81 faculty anesthesiologists. Provider-specific incidences of prolonged extubation were assessed by using unadjusted frequentist statistics and a Bayesian model adjusted for prone positioning, American Society of Anesthesiologist's base units, and case duration. RESULTS: 20.31% of extubations were "prolonged," and 40% of anesthesiologists were identified as outliers using a frequentist approach, that is, incidence greater than upper 95% CI (20.71%). With an adjusted Bayesian model, only one anesthesiologist was deemed an outlier. If an average anesthesiologist performed all extubations, the incidence of prolonged extubations would change negligibly (to 20.67%). If the anesthesiologist with the highest incidence of prolonged extubations was replaced with an average anesthesiologist, the change was also negligible (20.01%). Variability among anesthesiologists in the incidence of prolonged extubations was significantly less than among other providers. CONCLUSIONS: Bayesian methodology with covariate adjustment is better suited to performance monitoring than an unadjusted, nonhierarchical frequentist approach because it is less likely to identify individuals spuriously as outliers. Targeting outliers in an effort to alter operating room activities is unlikely to have an operational impact (although monitoring may serve other purposes). If change is deemed necessary, it must be made by improving the average behavior of everyone and by focusing on anesthesia providers rather than on faculty. PMID- 26545102 TI - Therapeutic Hypothermia in Post-Cardiac Arrest and Myocardial Infarction. PMID- 26545103 TI - Tuning reactivity and selectivity in hydrogen atom transfer from aliphatic C-H bonds to alkoxyl radicals: role of structural and medium effects. AB - Hydrogen atom transfer (HAT) is a fundamental reaction that takes part in a wide variety of chemical and biological processes, with relevant examples that include the action of antioxidants, damage to biomolecules and polymers, and enzymatic and biomimetic reactions. Moreover, great attention is currently devoted to the selective functionalization of unactivated aliphatic C-H bonds, where HAT based procedures have been shown to play an important role. In this Account, we describe the results of our recent studies on the role of structural and medium effects on HAT from aliphatic C-H bonds to the cumyloxyl radical (CumO(*)). Quantitative information on the reactivity and selectivity patterns observed in these reactions has been obtained by time-resolved kinetic studies, providing a deeper understanding of the factors that govern HAT from carbon and leading to the definition of useful guidelines for the activation or deactivation of aliphatic C-H bonds toward HAT. In keeping with the electrophilic character of alkoxyl radicals, polar effects can play an important role in the reactions of CumO(*). Electron-rich C-H bonds are activated whereas those that are alpha to electron withdrawing groups are deactivated toward HAT, with these effects being able to override the thermodynamic preference for HAT from the weakest C-H bond. Stereoelectronic effects can also influence the reactivity of the C-H bonds of ethers, amines, and amides. HAT is most rapid when these bonds can be eclipsed with a lone pair on an adjacent heteroatom or with the pi-system of an amide functionality, thus allowing for optimal orbital overlap. In HAT from cyclohexane derivatives, tertiary axial C-H bond deactivation and tertiary equatorial C-H bond activation have been observed. These effects have been explained on the basis of an increase in torsional strain or a release in 1,3-diaxial strain in the HAT transition states, with kH(eq)/kH(ax) ratios that have been shown to exceed one order of magnitude. Medium effects on HAT from aliphatic C-H bonds to CumO(*) have been also investigated. With basic substrates, from large to very large decreases in kH have been measured with increasing solvent hydrogen bond donor (HBD) ability or after addition of protic acids or alkali and alkaline earth metal ions, with kinetic effects that exceed 2 orders of magnitude in the reactions of tertiary alkylamines and alkanamides. Solvent hydrogen bonding, protonation, and metal ion binding increase the electron deficiency and the strength of the C-H bonds of these substrates deactivating these bonds toward HAT, with the extent of this deactivation being modulated by varying the nature of the substrate, solvent, protic acid, and metal ion. These results indicate that through these interactions careful control over the HAT reactivity of basic substrates toward CumO(*) and other electrophilic radicals can be achieved, suggesting moreover that these effects can be exploited in an orthogonal fashion for selective C-H bond functionalization of substrates bearing different basic functionalities. PMID- 26545104 TI - Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres. AB - Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart. PMID- 26545105 TI - A model-based comparison of three theories of audiovisual temporal recalibration. AB - Observers change their audio-visual timing judgements after exposure to asynchronous audiovisual signals. The mechanism underlying this temporal recalibration is currently debated. Three broad explanations have been suggested. According to the first, the time it takes for sensory signals to propagate through the brain has changed. The second explanation suggests that decisional criteria used to interpret signal timing have changed, but not time perception itself. A final possibility is that a population of neurones collectively encode relative times, and that exposure to a repeated timing relationship alters the balance of responses in this population. Here, we simplified each of these explanations to its core features in order to produce three corresponding six parameter models, which generate contrasting patterns of predictions about how simultaneity judgements should vary across four adaptation conditions: No adaptation, synchronous adaptation, and auditory leading/lagging adaptation. We tested model predictions by fitting data from all four conditions simultaneously, in order to assess which model/explanation best described the complete pattern of results. The latency-shift and criterion-change models were better able to explain results for our sample as a whole. The population-code model did, however, account for improved performance following adaptation to a synchronous adapter, and best described the results of a subset of observers who reported least instances of synchrony. PMID- 26545106 TI - Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees. AB - The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees. PMID- 26545107 TI - The Unfolding MD Simulations of Cyclophilin: Analyzed by Surface Contact Networks and Their Associated Metrics. AB - Currently, considerable interest exists with regard to the dissociation of close packed aminoacids within proteins, in the course of unfolding, which could result in either wet or dry moltenglobules. The progressive disjuncture of residues constituting the hydrophobic core ofcyclophilin from L. donovani (LdCyp) has been studied during the thermal unfolding of the molecule, by molecular dynamics simulations. LdCyp has been represented as a surface contactnetwork (SCN) based on the surface complementarity (Sm) of interacting residues within themolecular interior. The application of Sm to side chain packing within proteins make it a very sensitive indicator of subtle perturbations in packing, in the thermal unfolding of the protein. Network based metrics have been defined to track the sequential changes in the disintegration ofthe SCN spanning the hydrophobic core of LdCyp and these metrics prove to be highly sensitive compared to traditional metrics in indicating the increased conformational (and dynamical) flexibility in the network. These metrics have been applied to suggest criteria distinguishing DMG, WMG and transition state ensembles and to identify key residues involved in crucial conformational/topological events during the unfolding process. PMID- 26545108 TI - Knock-Down of the 37kDa/67kDa Laminin Receptor LRP/LR Impedes Telomerase Activity. AB - Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. Both the 37kDa/67kDa laminin receptor (LRP/LR) and telomerase are overexpressed in cancer cells. LRP/LR enhances the invasiveness of cancer cells thereby promoting metastasis, supporting angiogenesis and hampering apoptosis. An essential component of telomerase, hTERT is overexpressed in 85-90% of most cancers. hTERT expression and increased telomerase activity are associated with tumor progression. As LRP/LR and hTERT both play a role in cancer progression, we investigated a possible correlation between LRP/LR and telomerase. LRP/LR and hTERT co-localized in the perinuclear compartment of tumorigenic breast cancer (MDA_MB231) cells and non-tumorigenic human embryonic kidney (HEK293) cells. FLAG(r) Co-immunoprecipitation assays confirmed an interaction between LRP/LR and hTERT. In addition, flow cytometry revealed that both cell lines displayed high cell surface and intracellular LRP/LR and hTERT levels. Knock-down of LRP/LR by RNAi technology significantly reduced telomerase activity. These results suggest for the first time a novel function of LRP/LR in contributing to telomerase activity. siRNAs targeting LRP/LR may act as a potential alternative therapeutic tool for cancer treatment by (i) blocking metastasis (ii) promoting angiogenesis (iii) inducing apoptosis and (iv) impeding telomerase activity. PMID- 26545109 TI - Correction: Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis. PMID- 26545111 TI - Clinical Significance of MiR-137 Expression in Patients with Gastric Cancer After Radical Gastrectomy. AB - The dysregulation of miR-137 plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of gastric cancer patients remains unknown. This study was designed to investigate the expression and prognostic significance of miR-137 in gastric cancer patients after radical gastrectomy. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression of miR-137 in human gastric cancer cell lines and tissues in patients with gastric adenocarcinoma. Results were assessed for association with clinical factors and overall survival by using Kaplan-Meier analysis. Prognostic values of miR-137 expression and clinical outcomes were evaluated by Cox regression analysis. The results exhibited that the expression level of miR-137 was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-137 was associated with tumor cell differentiation, N stage, and TNM stage. Decreased miR-137 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients. Further multivariate Cox regression analysis suggested that miR-137 expression was an independent prognostic indicator for gastric cancer except for TNM stage. Applying the prognostic value of miR-137 expression to TNM stage III group showed a better risk stratification for overall survival. In conclusion, the results reinforced the critical role for the down-regulated miR-137 expression in gastric cancer and suggested that miR-137 expression could be a prognostic indicator for this disease. In addition, these patients with TNM stage III gastric cancer and low miR-137 expression might need more aggressive postoperative treatment and closer follow-up. PMID- 26545112 TI - Climate-Driven Phenological Change: Developing Robust Spatiotemporal Modeling and Projection Capability. AB - Our possibility to appropriately detect, interpret and respond to climate-driven phenological changes depends on our ability to model and predict the changes. This ability may be hampered by non-linearity in climate-phenological relations, and by spatiotemporal variability and scale mismatches of climate and phenological data. A modeling methodology capable of handling such complexities can be a powerful tool for phenological change projection. Here we develop such a methodology using citizen scientists' observations of first flight dates for orange tip butterflies (Anthocharis cardamines) in three areas extending along a steep climate gradient. The developed methodology links point data of first flight observations to calculated cumulative degree-days until first flight based on gridded temperature data. Using this methodology we identify and quantify a first flight model that is consistent across different regions, data support scales and assumptions of subgrid variability and observation bias. Model application to observed warming over the past 60 years demonstrates the model usefulness for assessment of climate-driven first flight change. The cross regional consistency of the model implies predictive capability for future changes, and calls for further application and testing of analogous modeling approaches to other species, phenological variables and parts of the world. PMID- 26545110 TI - Genetic Interactions Implicating Postreplicative Repair in Okazaki Fragment Processing. AB - Ubiquitination of the replication clamp proliferating cell nuclear antigen (PCNA) at the conserved residue lysine (K)164 triggers postreplicative repair (PRR) to fill single-stranded gaps that result from stalled DNA polymerases. However, it has remained elusive as to whether cells engage PRR in response to replication defects that do not directly impair DNA synthesis. To experimentally address this question, we performed synthetic genetic array (SGA) analysis with a ubiquitination-deficient K164 to arginine (K164R) mutant of PCNA against a library of S. cerevisiae temperature-sensitive alleles. The SGA signature of the K164R allele showed a striking correlation with profiles of mutants deficient in various aspects of lagging strand replication, including rad27Delta and elg1Delta. Rad27 is the primary flap endonuclease that processes 5' flaps generated during lagging strand replication, whereas Elg1 has been implicated in unloading PCNA from chromatin. We observed chronic ubiquitination of PCNA at K164 in both rad27Delta and elg1Delta mutants. Notably, only rad27Delta cells exhibited a decline in cell viability upon elimination of PRR pathways, whereas elg1Delta mutants were not affected. We further provide evidence that K164 ubiquitination suppresses replication stress resulting from defective flap processing during Okazaki fragment maturation. Accordingly, ablation of PCNA ubiquitination increased S phase checkpoint activation, indicated by hyperphosphorylation of the Rad53 kinase. Furthermore, we demonstrate that alternative flap processing by overexpression of catalytically active exonuclease 1 eliminates PCNA ubiquitination. This suggests a model in which unprocessed flaps may directly participate in PRR signaling. Our findings demonstrate that PCNA ubiquitination at K164 in response to replication stress is not limited to DNA synthesis defects but extends to DNA processing during lagging strand replication. PMID- 26545113 TI - An Enzyme from Aristolochia indica Destabilizes Fibrin-beta Amyloid Co-Aggregate: Implication in Cerebrovascular Diseases. AB - Fibrinogen and beta-amyloid (Abeta) peptide independently form ordered aggregates but in combination, they form disordered structures which are resistant to fibrinolytic enzymes like plasmin and cause severity in cerebral amyloid angiopathy (CAA). A novel enzyme of 31.3 kDa has been isolated from the root of the medicinal plant Aristolochia indica that showed fibrinolytic as well as fibrin-Abeta co-aggregate destabilizing properties. This enzyme is functionally distinct from plasmin. Thrombolytic action of the enzyme was demonstrated in rat model. The potency of the plant enzyme in degrading fibrin and fibrin-plasma protein (Abeta, human serum albumin, lysozyme, transthyretin and fibronectin) co aggregates was demonstrated by atomic force microscopy, scanning electron microscopy and confocal microscopy that showed better potency of the plant enzyme as compared to plasmin. Moreover, the plant enzyme inhibited localization of the co-aggregate inside SH-SY5Y human neuroblastoma cells and also co-aggregate induced cytotoxicity. Plasmin was inefficient in this respect. In the background of limited options for fragmentation of these co-aggregates, the plant enzyme may appear as a potential proteolytic enzyme. PMID- 26545115 TI - Health Economics in Medical Nutrition: An Emerging Science. AB - RATIONAL: The objective of this paper is to describe the applications of health economic theory to medical nutrition. BACKGROUND: The published literature provides evidence that medical nutrition, e.g. oral nutritional supplements, is an effective treatment for patients with disease related malnutrition. Malnutrition is associated with mortality risk and complication rates, including infections. Malnutrition is not a new problem and with an ageing population it continues to become a major public health concern as increasing age is associated with an increased risk of malnutrition. FINDINGS: This overview shows that in the case RCTs are providing the clinical evidence, there is no methodological difference between a cost-effectiveness analysis for pharmaceutical or nutrition. However, in nutrition the evidence may not always come from RCT data, but will be more often based on observational data. Therefore the clinical evidence of nutrition in itself is not the issue, but the handling of clinical evidence from observational studies. As the link between the consumption of a food product and a resulting health status is often more difficult to establish than the effect of a drug treatment it requires the further development of adapted methodologies in order to correctly predict the impact of food-related health effects and health economic outcomes from a broader perspective. PMID- 26545114 TI - Renal Lipotoxicity-Associated Inflammation and Insulin Resistance Affects Actin Cytoskeleton Organization in Podocytes. AB - In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity. Recently, the evidence suggests that renal lipid accumulation leads to glomerular damage and, more specifically, produces dysfunction in podocytes, key cells that compose and maintain the glomerular filtration barrier. Our aim was to analyze the early mechanisms underlying the development of renal disease associated with the process of lipotoxicity in podocytes. Our results show that treatment of podocytes with palmitic acid produced intracellular accumulation of lipid droplets and abnormal glucose and lipid metabolism. This was accompanied by the development of inflammation, oxidative stress and endoplasmic reticulum stress and insulin resistance. We found specific rearrangements of the actin cytoskeleton and slit diaphragm proteins (Nephrin, P-Cadherin, Vimentin) associated with this insulin resistance in palmitic-treated podocytes. We conclude that lipotoxicity accelerates glomerular disease through lipid accumulation and inflammation. Moreover, saturated fatty acids specifically promote insulin resistance by disturbing the cytoarchitecture of podocytes. These data suggest that renal lipid metabolism and cytoskeleton rearrangements may serve as a target for specific therapies aimed at slowing the progression of podocyte failure during metabolic syndrome. PMID- 26545116 TI - A Faster Triphosphorylation Ribozyme. AB - In support of the RNA world hypothesis, previous studies identified trimetaphosphate (Tmp) as a plausible energy source for RNA world organisms. In one of these studies, catalytic RNAs (ribozymes) that catalyze the triphosphorylation of RNA 5'-hydroxyl groups using Tmp were obtained by in vitro selection. One ribozyme (TPR1) was analyzed in more detail. TPR1 catalyzes the triphosphorylation reaction to a rate of 0.013 min-1 under selection conditions (50 mM Tmp, 100 mM MgCl2, 22 degrees C). To identify a triphosphorylation ribozyme that catalyzes faster triphosphorylation, and possibly learn about its secondary structure TPR1 was subjected to a doped selection. The resulting ribozyme, TPR1e, contains seven mutations relative to TPR1, displays a previously unidentified duplex that constrains the ribozyme's structure, and reacts at a 24 fold faster rate than the parent ribozyme. Under optimal conditions (150 mM Tmp, 650 mM MgCl2, 40 degrees C), the triphosphorylation rate of TRP1e reaches 6.8 min 1. PMID- 26545117 TI - Noncaloric Benefits of Carbohydrates. AB - Noncaloric benefits of carbohydrates are due to the presence of dietary fibers, which are a heterogeneous group of natural food sources and form an important component of a healthy diet. They differ in physiochemical properties such as solubility, fermentability and viscosity. They have a wide range of physiological effects resulting in gastrointestinal and systemic benefits. These include appetite, satiety, bowel transit time and function, production of short-chain fatty acids and certain vitamins, and effects on gut microbiota, immunity and inflammation, as well as mineral absorption. They also help to control the glycemic status and serum lipid levels, resulting in reduced incidence rates of atherosclerosis, hypertension, stroke and cardiovascular diseases. PMID- 26545118 TI - Molecular Insights into the Transmembrane Domain of the Thyrotropin Receptor. AB - The thyrotropin receptor (TSHR) is a G protein-coupled receptor (GPCR) that is member of the leucine-rich repeat subfamily (LGR). In the absence of crystal structure, the success of rational design of ligands targeting the receptor internal cavity depends on the quality of the TSHR models built. In this subfamily, transmembrane helices (TM) 2 and 5 are characterized by the absence of proline compared to most receptors, raising the question of the structural conformation of these helices. To gain insight into the structural properties of these helices, we carried out bioinformatics and experimental studies. Evolutionary analysis of the LGR family revealed a deletion in TM5 but provided no information on TM2. Wild type residues at positions 2.58, 2.59 or 2.60 in TM2 and/or at position 5.50 in TM5 were substituted to proline. Depending on the position of the proline substitution, different effects were observed on membrane expression, glycosylation, constitutive cAMP activity and responses to thyrotropin. Only proline substitution at position 2.59 maintained complex glycosylation and high membrane expression, supporting occurrence of a bulged TM2. The TSHR transmembrane domain was modeled by homology with the orexin 2 receptor, using a protocol that forced the deletion of one residue in the TM5 bulge of the template. The stability of the model was assessed by molecular dynamics simulations. TM5 straightened during the equilibration phase and was stable for the remainder of the simulations. Our data support a structural model of the TSHR transmembrane domain with a bulged TM2 and a straight TM5 that is specific of glycoprotein hormone receptors. PMID- 26545119 TI - Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-beta Signaling. AB - KSHV is a DNA tumor virus that causes Kaposi's sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-beta signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-beta signaling pathway by down-regulating SMAD2. Moreover, TGF-beta activity and SMAD2 expression were fully restored when antagomirs (inhibitors) of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-beta signaling pathway. Manipulation of the TGF-beta pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS. PMID- 26545121 TI - Costs of Foraging Predispose Animals to Obesity-Related Mortality when Food Is Constantly Abundant. AB - Obesity is an important medical problem affecting humans and animals in the developed world, but the evolutionary origins of the behaviours that cause obesity are poorly understood. The potential role of occasional gluts of food in determining fat-storage strategies for avoiding mortality have been overlooked, even though animals experienced such conditions in the recent evolutionary past and may follow the same strategies in the modern environment. Humans, domestic, and captive animals in the developed world are exposed to a surplus of calorie rich food, conditions characterised as 'constant-glut'. Here, we use a mathematical model to demonstrate that obesity-related mortality from poor health in a constant-glut environment should equal the average mortality rate in the 'pre-modern' environment when predation risk was more closely linked with foraging. It should therefore not be surprising that animals exposed to abundant food often over-eat to the point of ill-health. Our work suggests that individuals tend to defend a given excessive level of reserves because this level was adaptive when gluts were short-lived. The model predicts that mortality rate in constant-glut conditions can increase as the assumed health cost of being overweight decreases, meaning that any adaptation that reduced such health costs would have counter-intuitively led to an increase in mortality in the modern environment. Taken together, these results imply that efforts to reduce the incidence of obesity that are focussed on altering individual behaviour are likely to be ineffective because modern, constant-glut conditions trigger previously adaptive behavioural responses. PMID- 26545120 TI - SOST Inhibits Prostate Cancer Invasion. AB - Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings. PMID- 26545122 TI - Social Support of Patients with Type 2 Diabetes in Marginalized Contexts in Mexico and Its Relation to Compliance with Treatment: A Sociocultural Approach. AB - OBJECTIVE: This study aimed to describe the ways social support works in the daily life of patients with type 2 diabetes living in conditions of social and economic marginality, in order to understand how that support relates to treatment compliance. METHODS: Sequential mixed methods research was used. The sample of patients was obtained from primary health care units and selected considering regional representativeness, and levels of morbidity and mortality for type 2 diabetes. RESULTS: Results point to the nuclear family as the main source of support. Regardless of the area of residence, four main dimensions of support were identified: economic support, help with treatment compliance, emotional support, and material aid. CONCLUSIONS: We conclude that the support network assists the patient in different ways and helps cope with the disease, but in conditions of social and economic marginality, does not guarantee the quality of attention nor enable the self-management of treatment. PMID- 26545123 TI - Early SIV Dissemination After Intrarectal SIVmac251 Challenge Was Associated With Proliferating Virus-Susceptible Cells in the Colorectum. AB - OBJECTIVE: Few studies have examined the eclipse time of simian immunodeficiency virus/HIV infection through the anal route. We aimed to measure the eclipse time after SIVmac251 intrarectal inoculation, and to investigate the factor(s) associated with early dissemination. DESIGN: Forty macaques were intrarectally challenged with SIVmac251 3 times at 2-week intervals. METHODS: Plasma viral RNA was monitored at 4, 7, 11, 14, 21, and 28 days after infection. Rectal/vaginal tissues were obtained and tissue viral loads (VLs) were measured at day 14 postinfection. RESULTS: Of 40 macaques 26 (65%) had first detectable viral RNAs in the plasma at day 7 after the challenge that led to productive infection. Strikingly, 6 animals (15%) had detectable viral RNA in the plasma as early as at day 4. The Ki67 viral target CD4 T cells in the colorectal tissues were significantly higher in the early or middle-transmitter groups than those in the late-transmitter group. The rectal VL did not correlate with plasma VL at 14-day postinoculation, but did positively correlate with plasma VLs at days 21 and 28 postinfection. CONCLUSIONS: The median eclipse time after intrarectal challenge was 7 days, with a few early transmitters at 4 days. More rapid viral dissemination was associated with a high frequency of colorectal Ki67CCR5CD4T cells, which fuel the local viral replication. Furthermore, local viral replication in the colorectal tissue during the early stage might affect the plasma VL in a delayed manner. Therefore, to reduce/limit these target cells at the portal of viral entry is essential. PMID- 26545124 TI - Blocking CXCL9 Decreases HIV-1 Replication and Enhances the Activity of Prophylactic Antiretrovirals in Human Cervical Tissues. AB - OBJECTIVES: The interferon-gamma-induced chemokine CXCL9 is expressed in a wide range of inflammatory conditions including those affecting the female genital tract. CXCL9 promotes immune cell recruitment, activation, and proliferation. The role of CXCL9 in modulating HIV-1 infection of cervicovaginal tissues, a main portal of viral entry, however, has not been established. We report a link between CXCL9 and HIV-1 replication in human cervical tissues and propose CXCL9 as a potential target to enhance the anti-HIV-1 activity of prophylactic antiretrovirals. DESIGN: Using ex vivo infection of human cervical tissues as a model of mucosal HIV-1 acquisition, we described the effect of CXCL9 neutralization on HIV-1 gene expression and mucosal CD4 T-cell activation. The anti-HIV-1 activity of tenofovir, the leading mucosal pre-exposure prophylactic microbicide, alone or in combination with CXCL9 neutralization was also studied. METHODS: HIV-1 replication was evaluated by p24 ELISA. HIV-1 DNA and RNA, and CD4, CCR5, and CD38 transcription were evaluated by quantitative real-time polymerase chain reaction. Frequency of activated cervical CD4 T cells was quantified using fluorescence-activated cell sorting. RESULTS: Antibody blocking of CXCL9 reduced HIV-1 replication by decreasing mucosal CD4 T-cell activation. CXCL9 neutralization in combination with suboptimal concentrations of tenofovir, possibly present in the cervicovaginal tissues of women using the drug inconsistently, demonstrated an earlier and greater decrease in HIV-1 replication compared with tissues treated with tenofovir alone. CONCLUSIONS: CXCL9 neutralization reduces HIV-1 replication and may be an effective target to enhance the efficacy of prophylactic antiretrovirals. PMID- 26545126 TI - ["Give me a pill": the meanings of AIDS in bareback practice in Mexico City and its implications for HIV prevention]. AB - OBJECTIVE: To analyze and understand the meanings that gay men in Mexico City associate to unprotected sex such as bareback practices. MATERIALS AND METHODS: Exploratory qualitative study that uses grounded theory analysis of semistructured interviews with gay men that practice bareback sex recruited through the internet. Also a documentary analysis was performed. RESULTS: Gay men engage in bareback sexual practices because they have access to antiretroviral therapy. Access to treatment changes the meanings around AIDS and the perceived risk of infection. The confidence on treatment and the dropback of the Mexican government on preventive strategies explain these perceptions. CONCLUSIONS: Urban and middle class gay men in Mexico City have changed their perception with respect to HIV infection. It is necessary to understand the meanings related to bareback sexual practices and the use of condoms as a preventive strategy. We have to retake the discussion on preventive strategies, damage mitigation, stigma, discrimination, early diagnosis and the impact of antiretroviral therapy. PMID- 26545125 TI - Correlates of perceived risk of HIV infection among persons who inject drugs in Tijuana, Baja California, Mexico. AB - OBJECTIVE: We identified correlates of perceived risk of HIV infection among persons who inject drugs (PWID) in Tijuana. MATERIALS AND METHODS: PWID >=18 years of age who injected drugs in the past month were recruited between 2006 2007 and completed risk assessment interviews and serologic testing for HIV, syphilis, and tuberculosis. Logistic regression was used to determine factors associated with high-perceived risk of HIV infection. RESULTS: Among 974 PWID, HIV prevalence was 4.4%; 45.0% of participants perceived themselves to be more likely to become HIV infected relative to other PWID in Tijuana. Participants who reported high-perceived risk of HIV infection participated in high-risk behaviors such as injecting with used syringes, transactional sex, and were less likely to have had an HIV test. CONCLUSIONS: Recognition of HIV infection risk was associated with high risk behaviors and markers of vulnerability. Findings support efforts to encourage HIV testing and access to health care for this vulnerable population. PMID- 26545127 TI - [AIDS-related early mortality in Mexico between 2008 and 2012]. AB - OBJECTIVE: To describe the distribution of AIDS-related mortality according to the time of occurrence since entry to the System for the Administration, Logistics and Surveillance of Antiretrovirals (SALVAR, in Spanish), among users of Ministry of Health facilities in Mexico. MATERIALS AND METHODS: Descriptive analysis of AIDS mortality and the related clinical and demographic profile of 41847 patients registered in SALVAR. RESULTS: 3195 patients (8.1%) died within the study period, 59% of these deaths occurred within six months after treatment initiation. Among those patients, 87.3% were diagnosed late, given their CD4 levels (CD4cel<200 cel/ml3). CONCLUSION: Our results underscore the need to strengthen programs aimed to increase opportune HIV diagnosis and linkage to care, as a key component of universal access policy to antiretroviral treatment in Mexico. PMID- 26545128 TI - [Delayed initiation of antiretroviral therapy in Mexico]. AB - OBJECTIVE: To estimate the prevalence of delayed- initiation (DI) of antiretroviral therapy (ART) for people with HIV attended at the Ministry of Health (SS, for its initials in Spanish) in Mexico, and to describe its behavior over time (2008-2013) and differences by gender and age. MATERIALS AND METHODS: Descriptive and sectional study of people entering ART in the period 2008-2013 in the SS. The prevalence of DI ART (CD4+ <200 cells/ml) was estimated and differences according to sex and age were analyzed. RESULTS: The DI ART prevalence was 49%, having decreased 10% in the period. In men was 4.8% and 24.5% in women (p<0.01). The 15 to 29 years group also showed a decrease. CONCLUSIONS: Despite the decrease in ART DI prevalence, it still remains high. It is necessary to generate comprehensive screening strategies with multisectoral participation. PMID- 26545129 TI - [Psychosocial factors associated with late HAART initiation in Mexican patients with HIV]. AB - OBJECTIVE: To explore the association between psychosocial factors and late highly active antiretroviral therapy (HAART) initiation in a sample of Mexican patients with HIV. MATERIALS AND METHODS: We conducted a cross-sectional study at the HIV Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ), and applied structured questionnaires to 150 patients who initiated HAART between January 2010 and August 2011. Late HAART initiation (LHI) was considered when patients started HAART with CD4 counts of <200+ cells/mm3. RESULTS: By multivariate analysis, the strongest psychosocial risk factor for LHI observed was self-stigma towards HIV/AIDS. In addition, being tested by medical prescription, not by own initiative, as well as having one or more previous medical contacts, were associated with greater risk for LH. CONCLUSIONS: Our findings suggest the need to develop psychosocial interventions to decrease negative self-image and stigmatizing attitudes and behaviors in risk groups for HIV in Mexico. PMID- 26545130 TI - [Correcting for misclassified HIV/aids deaths in Mexico: Retrospective analysis, 1983-2012]. AB - OBJECTIVE: To identify and reassign misclassified AIDS deaths in Mexico, reconstructing the time series of mortality from 1983 to 2012, by state, sex, age, and affiliation to social security. MATERIALS AND METHODS: 15.5 million deaths from 1979 to 2012 were analyzed. The HIV-AIDS mortality correction was done in three phases: a) those causes directly related to AIDS; b) by miscoded deaths, and c) AIDS deaths hidden in other underlying causes of death. Age standardized rates of mortality (SMR) were calculated by sex, affiliation to social security, and state. RESULTS: 107 981 AIDS deaths from 1983 to 2012 were accumulated, representing 11% of total deaths observed for the period. The SMR in men for all age groups begins to decline since 1996, while for women the decline started in 2008. A similar picture is observed for the population with / without social security. Heterogeneity is a feature for SMR by state. CONCLUSION: An easily replicable methodology for the correction of mortality from AIDS, which generates relevant information for decision making based on the evidence is presented. PMID- 26545131 TI - [The role of supply-side characteristics of services in AIDS mortality in Mexico]. AB - OBJECTIVE: To document the association between supply-side determinants and AIDS mortality in Mexico between 2008 and 2013. MATERIALS AND METHODS: We analyzed the SALVAR database (system for antiretroviral management, logistics and surveillance) as well as data collected through a nationally representative survey in health facilities. We used multivariate logit regression models to estimate the association between supply-side characteristics, namely management, training and experience of health care providers, and AIDS mortality, distinguishing early and non-early mortality and controlling for clinical indicators of the patients. RESULTS: Clinic status of the patients (initial CD4 and viral load) explain 44.4% of the variability of early mortality across clinics and 13.8% of the variability in non-early mortality. Supply-side characteristics increase explanatory power of the models by 16% in the case of early mortality, and 96% in the case of non-early mortality. CONCLUSIONS: Aspects of management and implementation of services contribute significantly to explain AIDS mortality in Mexico. Improving these aspects of the national program, can similarly improve its results. PMID- 26545132 TI - [In-hospital mortality in HIV-infected patients: 10 years after the implementation of universal access to HAART in Mexico]. AB - OBJECTIVE: To establish the characteristics and causes of death of HIV patients who die while hospitalized. MATERIALS AND METHODS: We included HIV+ patients who died during hospitalization, in three hospitals in Mexico City between 2010 and 2013. Sociodemographic and clinical data were collected as well as causes of death. We identified preventable deaths (defined as deaths that occurred in patients with less than six months of HAART, or without HAART, with less than 350 CD4 at diagnosis and/or opportunistic events as the cause of hospitalization). RESULTS: 128 deaths were analyzed. The median of CD4 count was 47 cells/mm3; 18% of the patients ignored their HIV status at the time of hospitalization, 51% had less than six months of HAART, 40.5% had never received HAART before. The main causes of death were AIDS defining events, with 65.6%. We identified 70 preventable deaths (57%). CONCLUSIONS: Despite universal access to HAART, HIV patients in Mexico are still dying of AIDS defining illnesses, an indicator of late diagnosis. It is urgent to implement HIV testing programs to allow earlier diagnosis and make HAART benefit accessible to all. PMID- 26545133 TI - Antiretroviral purchasing and prescription practices in Mexico: constraints, challenges and opportunities. AB - OBJECTIVE: This study examines the antiretroviral (ARV) market characteristics for drugs procured and prescribed to Mexico's Social Protection System in Health beneficiaries between 2008 and 2013, and compares them with international data. MATERIALS AND METHODS: Procurement information from the National Center for the Prevention and the Control of HIV/AIDS was analyzed to estimate volumes and prices of key ARV. Annual costs were compared with data from the World Health Organization's Global Price Reporting Mechanism for similar countries. Finally, regimens reported in the ARV Drug Management, Logistics and Surveillance System database were reviewed to identify prescription trends and model ARV expenditures until 2018. RESULTS: Results show that the first-line ARV market is concentrated among a small number of patented treatments, in which prescription is clinically adequate, but which prices are higher than those paid by similar countries. The current set of legal and structural options available to policy makers to bring prices down is extremely limited. CONCLUSIONS: Different negotiation policies were not successful to decrease ARV high prices in the public health market. The closed list approach had a good impact on prescription quality but was ineffective in reducing prices. The Coordinating Commission for Negotiating the Price of Medicines and other Health Supplies also failed to obtain adequate prices. To maximize purchase efficiency, policy makers should focus on finding long-term legal and political safeguards to counter the high prices imposed by pharmaceutical companies. PMID- 26545134 TI - [Inconsistent condom use among Mexican women living with HIV: a challenge for health services]. AB - OBJECTIVE: To describe condom use among Mexican women living with HIV and analyze factors that facilitate or impede its utilization. MATERIALS AND METHODS: Qualitative analysis of 55 interviews with women of reproductive age living with HIV. RESULTS: Inconsistent condom use and non-use at last sexual intercourse was common, and not clearly related to the male partners' HIV-status. Factors that influenced condom use included perceptions of health benefits, symbolic meaning assigned to the condom within the relationship, and the transformation or persistence of inequitable gender norms. CONCLUSIONS: Gender norms and male partners' attitudes strongly influence condom use among women living with HIV. To increase consistent condom use the health system must implement counseling and service delivery with a gender perspective and innovative actions to involve male partners. PMID- 26545135 TI - [Discrimination and homophobia associated to the human immunodeficiency virus epidemic]. AB - OBJECTIVE: To describe a political mapping on discrimination and homophobia associated to human immunodeficiency virus (HIV) in the context of public institutions in Mexico. MATERIALS AND METHODS: The political mapping was conducted in six Mexican states. Stakeholders who were involved in HIV actions from public and private sectors were included. Semistructured interviews were applied to explore homophobia and discrimination associated with HIV. Information was systematized using the Policy Maker software, which is a good support for analyzing health policies. RESULTS: Discriminatory and homophobic practices in the public domain occurred, damaging people's integrity via insults, derision and hate crimes. Most stakeholders expressed a supportive position to prevent discrimination and homophobia and some of them had great influence on policy making decisions. It was found that state policy frameworks are less specific in addressing these issues. CONCLUSIONS: Homophobia and discrimination associated to HIV are still considered problematic in Mexico. Homophobia is a very sensitive issue that requires further attention. Also, an actual execution of governmental authority requires greater enforcement of laws against discrimination and homophobia. PMID- 26545136 TI - [Editorial]. PMID- 26545137 TI - HIV prevalence, sociodemographic characteristics, and sexual behaviors among transwomen in Mexico City. AB - OBJECTIVE: To present results from HIV testing, knowledge of HIV status and socioeconomic factors associated with the probability of having a HIV positive result among transwomen (TW) in Mexico. MATERIALS AND METHODS: In 2012, we conducted an HIV seroprevalence survey to 585 TW in Mexico City in three strata: gathering places, the Condesa HIV Clinic and in four detention centers. We estimated the prevalence of HIV in each strata and applied a probit model to the overall sample to analyze factors associated with the probability of a HIV positive result. RESULTS: The prevalence of HIV was 19.8% in meeting places; 31.9% in detention centers and 64% among the participants of the clinic. Age, low education and number of sexual partners was positively associated with HIV. CONCLUSIONS: Results from the study provide relevant information to design HIV prevention interventions tailored to the needs of the TW population. PMID- 26545138 TI - Controlling shape and position of vascular formation in engineered tissues by arbitrary assembly of endothelial cells. AB - Cellular self-assembly based on cell-to-cell communication is a well-known tissue organizing process in living bodies. Hence, integrating cellular self-assembly processes into tissue engineering is a promising approach to fabricate well organized functional tissues. In this research, we investigated the capability of endothelial cells (ECs) to control shape and position of vascular formation using arbitral-assembling techniques in three-dimensional engineered tissues. To quantify the degree of migration of ECs in endothelial network formation, image correlation analysis was conducted. Positive correlation between the original positions of arbitrarily assembled ECs and the positions of formed endothelial networks indicated the potential for controlling shape and position of vascular formations in engineered tissues. To demonstrate the feasibility of controlling vascular formations, engineered tissues with vascular networks in triangle and circle patterns were made. The technique reported here employs cellular self assembly for tissue engineering and is expected to provide fundamental beneficial methods to supply various functional tissues for drug screening and regenerative medicine. PMID- 26545139 TI - Visual objects speak louder than words: motor planning and weight in tool use and object transport. AB - For theories of embodied cognition, reading a word activates sensorimotor representations in a similar manner to seeing the physical object the word represents. Thus, reading words representing objects of different sizes interfere with motor planning, inducing changes in grip aperture. An outstanding issue is whether word reading can also evoke sensorimotor information about the weight of objects. This issue was addressed in two experiments wherein participants have first to read the name of an object (Experiment 1)/observe the object (Experiment 2) and then to transport versus use bottles of water. The objects presented as primes were either lighter or heavier than the bottles to be grasped. Results indicated that the main parameters of motor planning recorded (initiation times and finger contact points) were not affected by the presentation of words as primes (Experiment 1). By contrast, the presentation of visual objects as primes induced significant changes in these parameters (Experiment 2). Participants changed their way of grasping the bottles, particularly in the use condition. Taken together, these results suggest that the activation of concepts does not automatically evoke sensorimotor representations about the weight of objects, but visual objects do. PMID- 26545140 TI - Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design. AB - Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. PMID- 26545142 TI - Ventilation/perfusion distributions revisited. AB - PURPOSE OF REVIEW: A major cause of hypoxemia in anesthesia is ventilation perfusion (VA/Q) mismatch. With more advanced surgery and an aging population, monitoring of VA/Q is of increasing importance. RECENT FINDINGS: The classic multiple inert gas elimination technique has been simplified with a new approach based on mass spectrometry. VA/Q distributions can also be measured, at the bedside, by varying inspired oxygen concentration. MRI, 3-dimensional single photon emission computed tomography, positron emission tomography, and electrical impedance tomography enable imaging of perfusion and ventilation, and in some of the techniques also the distribution of inflammation. One-lung ventilation with thoracoscopy and capnothorax require careful monitoring of VA/Q, made possible bedside by electrical impedance tomography. Carbon dioxide, but not air, for pneumoperitoneum enhances shift of perfusion to ventilated regions. Ventilatory support during cardiopulmonary resuscitation causes less VA/Q mismatch when inspired oxygen concentrations are lower. Mechanisms of redistribution of lung blood flow by inhaled nitric oxide include endothelin-mediated vasoconstriction in collapsed lung regions. SUMMARY: Methods are continuously developing to simplify measurement of VA/Q and also to relate VA/Q to inflammation. The recording of VA/Q has helped to explain important aspects of gas exchange in thoracic anesthesiology and in intensive care medicine. PMID- 26545141 TI - Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial. AB - OBJECTIVE: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. DESIGN: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. SETTING: Tertiary care children's hospital. PATIENTS: Children (0-18years) with ARDS undergoing mechanical ventilation. INTERVENTIONS: 35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. RESULTS: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1alpha, IFN-gamma and IL-10 levels. The glucocorticoid group had lower INF-alpha, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17alpha levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. CONCLUSION: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes. PMID- 26545143 TI - Systolic heart failure: diagnosis and therapy. AB - PURPOSE OF REVIEW: The present review highlights recent findings on perioperative systolic heart failure. It briefly summarizes the pathophysiology of heart failure and provides the reader with new insight in diagnosis and treatment of systolic heart failure. In addition, we review new therapeutic strategies with pharmacologic agents and mechanical assist devices to treat systolic heart failure. RECENT FINDINGS: Left ventricular systolic heart failure is a high-risk disease for patients undergoing cardiac and noncardiac surgery and poses a high burden on the anesthesiologist in charge. Perioperative echocardiography is well established for urgent diagnosis in the operating room and is superior to biomarker-based diagnosis. Although cardiovascular disease associated mortality decreases, systolic heart failure related mortality remains at a high of 50% after 5 years. As a consequence, left ventricular assist device implantation rates grow rapidly and include approximately 30-40% patients with desperate clinical situation and destination therapy. Extracorporeal life support for acute heart failure needs further investigation to document possible indications and side-effects. SUMMARY: Recent advances in the field of cardiovascular anesthesiology comprise advanced use of perioperative echocardiography, mechanical circulatory assist devices, and customized pharmacologic management. PMID- 26545145 TI - Lung transplantation: from the procedure to managing patients with lung transplantation. AB - PURPOSE OF REVIEW: The perioperative management of lung transplantation patients remains a challenge. The most important goal is the prevention or attenuation of primary graft failure due to ischemia and reperfusion, operative trauma, and activation of systemic inflammation; it significantly influences short-long and long-term outcome. This review focuses on different aspects regarding the management of these high-risk patients. RECENT FINDINGS: The Lung Allocation Score was implemented to estimate the survival benefit from a lung transplant. As scarcity of lung grafts persists new techniques such as the ex-vivo lung perfusion might allow for expanding the criteria and distribution range of donor organs. Thoracic anesthesia for lung transplantation faces the challenge to manage impaired oxygenation, refractory hypercapnia, and severe pulmonary hypertension in order to attenuate the risk of primary graft failure. Further, lung protective ventilator strategies to prevent postoperative acute lung injury might have an impact on outcome. This includes extracorporeal circulation therapy as rapid advances in this field open up new possibilities. Recent findings suggest that particular attention should be paid to neurocognitive outcome. SUMMARY: There is evidence that important key strategies improve outcome after lung transplantation. An update on the substantial challenges in anesthesia comprises ventilator strategy and the use of extracorporeal circulation to minimize inflammation associated with primary graft failure. PMID- 26545144 TI - Obstructive sleep apnea, pain, and opioids: is the riddle solved? AB - PURPOSE OF REVIEW: Perioperative opioid-based pain management of patients suffering from obstructive sleep apnea (OSA) may present challenges because of concerns over severe ventilatory compromise. The interaction between intermittent hypoxia, sleep fragmentation, pain, and opioid responses in OSA, is complex and warrants a special focus of perioperative outcomes research. RECENT FINDINGS: Life-threatening opioid-related respiratory events are rare. Epidemiologic evidence suggests that OSA together with other serious renal and heart disease, is among those conditions predisposing patients for opioid-induced ventilatory impairment (OIVI) in the postoperative period. Both intermittent hypoxia and sleep fragmentation, two distinct components of OSA, enhance pain. Intermittent hypoxia may also potentiate opioid analgesic effects. Activation of major inflammatory pathways may be responsible for the effects of sleep disruption and intermittent hypoxia on pain and opioid analgesia. Recent experimental evidence supports that these, seemingly contrasting, phenotypes of pain-increasing and opioid-enhancing effects of intermittent hypoxia, are not mutually exclusive. Although the effect of intermittent hypoxia on OIVI has not been elucidated, opioids worsen postoperative sleep-disordered breathing in OSA patients. A subset of these patients, characterized by decreased chemoreflex responsiveness and high arousal thresholds, might be at higher risk for OIVI. SUMMARY: OSA may complicate opioid-based perioperative management of pain by altering both pain processing and sensitivity to opioid effect. PMID- 26545146 TI - Preoxygenation and intraoperative ventilation strategies in obese patients: a comprehensive review. AB - PURPOSE OF REVIEW: Obesity along with its pathophysiological changes increases risk of intraoperative and perioperative respiratory complications. The aim of this review is to highlight recent updates in preoxygenation techniques and intraoperative ventilation strategies in obese patients to optimize gas exchange and pulmonary mechanics and reduce pulmonary complications. RECENT FINDINGS: There is no gold standard in preoxygenation or intraoperative ventilatory management protocol for obese patients. Preoxygenation in head up or sitting position has been shown to be superior to supine position. Apneic oxygenation and use of continuous positive airway pressure increases safe apnea duration. Recent evidence encourages the intraoperative use of low tidal volume to improve oxygenation and lung compliance without adverse effects. Contrary to nonobese patients, some studies have reported the beneficial effect of recruitment maneuvers and positive end-expiratory pressure in obese patients. No difference has been observed between volume controlled and pressure controlled ventilation. SUMMARY: The ideal ventilatory plan for obese patients is indeterminate. A multimodal preoxygenation and intraoperative ventilation plan is helpful in obese patients to reduce perioperative respiratory complications. More studies are needed to identify the role of low tidal volume, positive end-expiratory pressure, and recruitment maneuvers in obese patients undergoing general anesthesia. PMID- 26545147 TI - Anaesthesia for thymectomy in adult and juvenile myasthenic patients. AB - PURPOSE OF REVIEW: Myasthenia gravis, a chronic disease of the neuromuscular junction, is associated with an interaction with neuromuscular blocking agents (NMBAs). As thymectomy is often the method of choice for its treatment, anaesthetic management requires meticulous preoperative evaluation, careful monitoring, and adequate dose titration. The frequency of video-assisted thoracoscopic extended thymectomy (VATET) is also increasing, making the use of NMBA obligatory. The number of cases of the juvenile form has also increased over years; airway management in juvenile one-lung ventilation is another challenge. RECENT FINDINGS: Sugammadex appears to be a safe choice to avoid prolonged action of NMBA also in patients with myasthenia gravis, although this information has to be confirmed in further series. The number of VATETs is increasing so that the experience with sugammadex will also increase in time. In non-VATET operations, use of NMBA should and can be avoided as much as possible. New scoring systems are defined to predict a postoperative myasthenic crisis. For VATET in juvenile cases, blockers can be a good option for the airway management. SUMMARY: Anaesthetic management of thymectomy in myasthenia gravis requires experience concerning different approaches. Sugammadex should be considered as a possible further step toward postoperative safety. PMID- 26545149 TI - Effects of dexmedetomidine on emergence delirium in pediatric cardiac surgery. AB - BACKGROUND: The present study aimed to investigate the effects of dexmedetomidine on emergence delirium (ED) in pediatric patients undergoing cardiac surgery. METHODS: Fifty children of both sexes aged 1-6 years weighing 10-25 kilograms, with American Society of Anesthesiologists (ASA) physical status grade II, undergoing sevoflurane-based general anesthesia for elective cardiac surgery, were randomly assigned to two groups. The dexmedetomidine group (group D, N.=25) received 0.5 ug/kg of dexmedetomidine over 10 minutes, followed by an infusion at 0.5 ug/kg/h until the end of the surgery, whereas the saline group (group S, N.=25) received volume-matched normal saline immediately after the induction of anesthesia. Blood samples were taken preoperatively (T0), at different time points during surgery (T1-T5), and during the postoperative period (T6-T7) to determine serum melatonin, cortisol, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and blood glucose levels. In the cardiac intensive care unit (CICU), the incidence of ED was assessed with a 5-point scale, and the severity of ED was assessed with the Pediatric Anesthesia Emergence Delirium scale (PAED) every two hours for the first 24 hours after surgery. ED was considered when the 5-point scale score was >=4 for more than 5 minutes, or the PAED score was >=10. RESULTS: Based on comparable demographic profiles, the scores of the 5-point scale and PAED Scale were significantly lower in group D compared with group S (P=0.028 and P=0.009, respectively). In addition, the fluctuation in the level of melatonin was significantly less in group D. Serum cortisol, norepinephrine, IL-6, TNF-alpha and glucose levels were increased in the two groups, but these increases were significantly less in group D than in group S. The consumption of sevoflurane during anesthesia was significantly less in group D (P=0.0002). The postoperative consumption of fentanyl was less in group D (P=0.04), whereas the pain scores were not significantly different (P=0.502). Extubation time was significantly delayed in group D compared with group S (P=0.032), whereas CICU and hospital stay were comparable between the two groups. CONCLUSIONS: Continuous intraoperative infusions of dexmedetomidine in pediatric patients undergoing cardiac surgery reduce sevoflurane requirements and decrease the incidence of ED, which is associated with decreasing plasma melatonin levels and surgical stress. PMID- 26545148 TI - Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study. AB - BACKGROUND: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. OBJECTIVE: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). METHODS: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5 hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. RESULTS: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, SigmaDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of SigmaDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. CONCLUSIONS: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. CITATION: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760. PMID- 26545150 TI - Synthesis of Nitrogen-Doped Graphene Quantum Dots at Low Temperature for Electrochemical Sensing Trinitrotoluene. AB - Nitrogen-doped graphene quantum dots (N-GQDs) are synthesized at low temperature as a new catalyst allowing electrochemical detection of 2,4,6-trinitrotoluene (TNT). N-GQDs are made by an oxidative ultrasonication of graphene oxide (GO) forming nanometer-sized species, which are then chemically reduced and nitrogen doped by reacting with hydrazine. The as-synthesized N-GQDs have an average diameter of ~2.5 nm with an N/C atomic ratio of up to ~6.4%. To detect TNT, TNT is first accumulated on N-GQDs modified glassy carbon (N-GQDs/GC) electrode by holding the electrode at a 0 V versus Ag/AgCl for 150 s in an aqueous TNT solution. Next, the N-GQDs/GC electrode with accumulated TNT is transferred to a fresh PBS solution (0.1 M, pH 7.0, without TNT), where the TNT reduction current at -0.36 V versus Ag/AgCl in a linear scan voltammogram (LSV) shows a linear response to TNT concentration in the aqueous solution from 1 to 400 ppb, with a correlation coefficient of 0.999, a detection limit of 0.2 ppb at a signal/noise (S/N) of 3, and a detection sensitivity of 363 +/- 7 mA mM(-1) cm(-2). The detection limit of 0.2 ppb of TNT for this new method is much lower than 2 ppb set by the U.S. Environmental Protection Agency for drinking water. Therefore, N GQDs allow an electrochemical method for assaying TNT in drinking water to determine if levels of TNT are safe or not. PMID- 26545151 TI - Arrested Phase Separation of Elastin-like Polypeptide Solutions Yields Stiff, Thermoresponsive Gels. AB - The preparation of new responsive hydrogels is crucial for the development of soft materials for various applications, including additive manufacturing and biomedical implants. Here, we report the discovery of a new mechanism for forming physical hydrogels by the arrested phase separation of a subclass of responsively hydrophobic elastin-like polypeptides (ELPs). When moderately concentrated solutions of ELPs with the pentapeptide repeat (XPAVG)n (where X is either 20% or 60% valine with the remainder isoleucine) are warmed above their inverse transition temperature, phase separation becomes arrested, and hydrogels can be formed with shear moduli on the order of 0.1-1 MPa at 20 wt % in water. The longest stress relaxation times are well beyond 10(3) s. This result is surprising because ELPs are classically known for thermoresponsive coacervation that leads to macrophase separation, and solids are typically formed in the bulk or by supplemental cross-linking strategies. This new mechanism can form gels with remarkable mechanical behavior based on simple macromolecules that can be easily engineered. Small angle scattering experiments indicate that phase separation arrests to form a network of nanoscale domains, exhibiting rheological and structural features consistent with an arrested spinodal decomposition mechanism. Gel nanostructure can be modeled as a disordered bicontinuous network with interdomain, intradomain, and curvature length scales that can be controlled by sequence design and assembly conditions. These studies introduce a new class of reversible, responsive materials based on a classic artificial biopolymer that is a versatile platform to address critical challenges in industrial and medical applications. PMID- 26545152 TI - Vitamin D Deficiency and Increased Risk of Bladder Carcinoma: A Meta-Analysis. AB - BACKGROUND/AIMS: Vitamin D status in relation to bladder carcinoma risk was still inconsistent. This study was carried out to evaluate the relationship between vitamin D status and bladder carcinoma risk through a meta-analysis approach. METHODS: Pubmed, Web of Science, CNKI, and Embase were searched systemically to find eligible studies from the earliest available date to April 16, 2015. The search terms "vitamin D", "25-hydroxyvitamin D", "bladder cancer" or "bladder carcinoma" were used to retrieve relevant studies. The exposure of interest was intake of vitamin D or serum vitamin D levels, and the outcome of interest was bladder carcinoma incidence or mortality. The pooled risk ratio (RR) values and their 95%CIs were calculated through meta-analysis. RESULTS: Seven studies with a total of 62,141 participants met the inclusion criteria and were finally included into the meta-analysis. There was no heterogeneity among those included studies (I2 = 0%, P = 0.53). The pooled RR of bladder carcinoma for the lowest category versus the highest category of vitamin D was 1.34 (95% CI 1.17-1.53, P < 0.0001). Sensitivity analysis by omitting one study by turns showed all the pooled RRs were statistically significant. Meta-analysis of 5 studies reporting outcomes of serum vitamin D levels also showed that the low serum vitamin D level was associated with increased risk of bladder carcinoma (RR = 1.32, 95%CI 1.15-1.52, P = 0.0001). No obvious risk of publication bias was observed. CONCLUSION: Vitamin D deficiency is associated with increased risk of bladder carcinoma in present study. PMID- 26545153 TI - Ultra-Low Carbon Emissions from Coal-Fired Power Plants through Bio-Oil Co-Firing and Biochar Sequestration. AB - This study investigates a novel strategy of reducing carbon emissions from coal fired power plants through co-firing bio-oil and sequestering biochar in agricultural lands. The heavy end fraction of bio-oil recovered from corn stover fast pyrolysis is blended and co-fired with bituminous coal to form a bio-oil co firing fuel (BCF). Life-cycle greenhouse gas (GHG) emissions per kWh electricity produced vary from 1.02 to 0.26 kg CO2-eq among different cases, with BCF heavy end fractions ranging from 10% to 60%, which corresponds to a GHG emissions reduction of 2.9% to 74.9% compared with that from traditional bituminous coal power plants. We found a heavy end fraction between 34.8% and 37.3% is required to meet the Clean Power Plan's emission regulation for new coal-fired power plants. The minimum electricity selling prices are predicted to increase from 8.8 to 14.9 cents/kWh, with heavy end fractions ranging from 30% to 60%. A minimum carbon price of $67.4 +/- 13 per metric ton of CO2-eq was estimated to make BCF power commercially viable for the base case. These results suggest that BCF co firing is an attractive pathway for clean power generation in existing power plants with a potential for significant reductions in carbon emissions. PMID- 26545154 TI - Enantioselective Alkyne Addition to Aliphatic, Aromatic, and Vinyl Aldehydes Using Zn, (i)PrI, H8BINOL, and Ti(O(i)Pr)4. AB - A new catalytic system based on the readily available Zn, (i)PrI, H8BINOL, and Ti(O(i)Pr)4 has been developed which avoids the use of pyrophoric ZnEt2. It can effectively catalyze the reaction of various terminal alkynes with aromatic, aliphatic, and vinyl aldehydes to generate chiral propargylic alcohols at room temperature with up to 98% yield and 98% enantiomeric excess. This new system signifciantly expands the substrate scope of the previously reported system using Zn, EtI, BINOL, and Ti(O(i)Pr)4. PMID- 26545156 TI - Additivity of the Specific Effects of Additives on Protein Phase Behavior. AB - Protein phase behavior and protein-protein interactions can be tuned by additives. We experimentally determined the phase behavior of lysozyme solutions, namely, the cloud-point temperature (CPT), in the presence of two additives, sodium chloride (NaCl) and guanidine hydrochloride (GuHCl). Their concentrations are chosen to maintain the secondary structure, as verified by CD spectroscopy. Our data indicate that the salts affect the CPT through electrostatic screening and salt-specific contributions. At high salt concentrations, the CPT is a linear function of the additive concentration for the salts NaCl and GuHCl as well as for a nonionic additive, glycerol, and a solvent, dimethyl sulfoxide (DMSO). Their molar temperature increments, which rank their specific effects on the CPT (NaCl > 0 > DMSO > glycerol > GuHCl), are found to be essentially independent of the protein concentration. In particular, the specific effects of NaCl and GuHCl in mixtures are found to be additive, indicating the absence of synergies or suppressions between both salts. Thus, molar temperature increments represent a characteristic measure for the specific effects of additives on protein interactions, which is easily accessible in lab experiments and which will help to characterize the effects of additives on protein interactions and phase behavior. PMID- 26545155 TI - Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin-Biotin Interactions. AB - Cell-adhesive particles are of significant interest in biotechnology, the bioengineering of complex tissues, and biomedical research. Their applications range from platforms to increase the efficiency of anchorage-dependent cell culture to building blocks to loading cells in heterogeneous structures to clonal population growth monitoring to cell sorting. Although useful, currently available cell-adhesive particles can accommodate only homogeneous cell culture. Here, we report the design of anisotropic hydrogel microparticles with tunable cell-adhesive regions as first step toward micropatterned cell cultures on particles. We employed stop flow lithography (SFL), the coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin-biotin chemistry to adjust the localization of conjugated collagen and poly-L-lysine on the surface of microscale particles. Using the new particles, we demonstrate the attachment and formation of tight junctions between brain endothelial cells. We also demonstrate the geometric patterning of breast cancer cells on particles with heterogeneous collagen coatings. This new approach avoids the exposure of cells to potentially toxic photoinitiators and ultraviolet light and decouples in time the microparticle synthesis and the cell culture steps to take advantage of the most recent advances in cell patterning available for traditional culture substrates. PMID- 26545157 TI - Shape-Controlled Narrow-Gap SnTe Nanostructures: From Nanocubes to Nanorods and Nanowires. AB - The rational design and synthesis of narrow-gap colloidal semiconductor nanocrystals (NCs) is an important step toward the next generation of solution processable photovoltaics, photodetectors, and thermoelectric devices. SnTe NCs are particularly attractive as a Pb-free alternative to NCs of narrow-gap lead chalcogenides. Previous synthetic efforts on SnTe NCs have focused on spherical nanoparticles. Here we report new strategies for synthesis of SnTe NCs with shapes tunable from highly monodisperse nanocubes, to nanorods (NRs) with variable aspect ratios, and finally to long, straight nanowires (NWs). Reaction at high temperature quickly forms thermodynamically favored nanocubes, but low temperatures lead to elongated particles. Transmission electron microscopy studies of reaction products at various stages of the synthesis reveal that the growth and shape-focusing of monodisperse SnTe nanocubes likely involves interparticle ripening, while directional growth of NRs and NWs may be initiated by particle dimerization via oriented attachment. PMID- 26545158 TI - Advances in Artificial Life: Synthesis and Simulation of Living Systems: Editorial. PMID- 26545159 TI - Multi-crease Self-folding by Global Heating. AB - This study demonstrates a new approach to autonomous folding for the body of a 3D robot from a 2D sheet, using heat. We approach this challenge by folding a 0.27 mm sheetlike material into a structure. We utilize the thermal deformation of a contractive sheet sandwiched by rigid structural layers. During this baking process, the heat applied on the entire sheet induces contraction of the contracting layer and thus forms an instructed bend in the sheet. To attain the targeted folding angles, the V-fold spans method is used. The targeted angle thetaout can be kinematically encoded into crease geometry. The realization of this angle in the folded structure can be approximately controlled by a contraction angle thetain. The process is non-reversible, is reliable, and is relatively fast. Our method can be applied simultaneously to all the folds in multi-crease origami structures. We demonstrate the use of this method to create a lightweight mobile robot. PMID- 26545160 TI - The Search for Candidate Relevant Subsets of Variables in Complex Systems. AB - We describe a method to identify relevant subsets of variables, useful to understand the organization of a dynamical system. The variables belonging to a relevant subset should have a strong integration with the other variables of the same relevant subset, and a much weaker interaction with the other system variables. On this basis, extending previous work on neural networks, an information-theoretic measure, the dynamical cluster index, is introduced in order to identify good candidate relevant subsets. The method does not require any previous knowledge of the relationships among the system variables, but relies on observations of their values over time. We show its usefulness in several application domains, including: (i) random Boolean networks, where the whole network is made of different subnetworks with different topological relationships (independent or interacting subnetworks); (ii) leader-follower dynamics, subject to noise and fluctuations; (iii) catalytic reaction networks in a flow reactor; (iv) the MAPK signaling pathway in eukaryotes. The validity of the method has been tested in cases where the data are generated by a known dynamical model and the dynamical cluster index is applied in order to uncover significant aspects of its organization; however, it is important that it can also be applied to time series coming from field data without any reference to a model. Given that it is based on relative frequencies of sets of values, the method could be applied also to cases where the data are not ordered in time. Several indications to improve the scope and effectiveness of the dynamical cluster index to analyze the organization of complex systems are finally given. PMID- 26545161 TI - Indirectly Encoding Running and Jumping Sodarace Creatures for Artificial Life. AB - This article presents a lightweight platform for evolving two-dimensional artificial creatures. The aim of providing such a platform is to reduce the barrier to entry for researchers interested in evolving creatures for artificial life experiments. In effect the novel platform, which is inspired by the Sodarace construction set, makes it easy to set up creative scenarios that test the abilities of Sodarace-like creatures made of masses and springs. In this way it allows the researcher to focus on evolutionary algorithms and dynamics. The new indirectly encoded Sodarace (IESoR) system introduced in this article extends the original Sodarace by enabling the evolution of significantly more complex and regular creature morphologies. These morphologies are themselves encoded by compositional pattern-producing networks (CPPNs), an indirect encoding previously shown effective at encoding regularities and symmetries in structure. The capability of this lightweight system to facilitate research in artificial life is then demonstrated through both walking and jumping domains, in which IESoR discovers a wide breadth of strategies through novelty search with local competition. PMID- 26545162 TI - Experiments on and Numerical Modeling of the Capture and Concentration of Transcription-Translation Machinery inside Vesicles. AB - Synthetic or semi-synthetic minimal cells are those cell-like artificial compartments that are based on the encapsulation of molecules inside lipid vesicles (liposomes). Synthetic cells are currently used as primitive cell models and are very promising tools for future biotechnology. Despite the recent experimental advancements and sophistication reached in this field, the complete elucidation of many fundamental physical aspects still poses experimental and theoretical challenges. The interplay between solute capture and vesicle formation is one of the most intriguing ones. In a series of studies, we have reported that when vesicles spontaneously form in a dilute solution of proteins, ribosomes, or ribo-peptidic complexes, then, contrary to statistical predictions, it is possible to find a small fraction of liposomes (<1%) that contain a very large number of solutes, so that their local (intravesicular) concentrations largely exceed the expected value. More recently, we have demonstrated that this effect (spontaneous crowding) operates also on multimolecular mixtures, and can drive the synthesis of proteins inside vesicles, whereas the same reaction does not proceed at a measurable rate in the external bulk phase. Here we firstly introduce and discuss these already published observations. Then, we present a computational investigation of the encapsulation of transcription-translation (TX TL) machinery inside vesicles, based on a minimal protein synthesis model and on different solute partition functions. Results show that experimental data are compatible with an entrapment model that follows a power law rather than a Gaussian distribution. The results are discussed from the viewpoint of origin of life, highlighting open questions and possible future research directions. PMID- 26545163 TI - Lessons from Speciation Dynamics: How to Generate Selective Pressure Towards Diversity. AB - Recent approaches in evolutionary robotics (ER) propose to generate behavioral diversity in order to evolve desired behaviors more easily. These approaches require the definition of a behavioral distance, which often includes task specific features and hence a priori knowledge. Alternative methods, which do not explicitly force selective pressure towards diversity (SPTD) but still generate it, are known from the field of artificial life, such as in artificial ecologies (AEs). In this study, we investigate how SPTD is generated without task-specific behavioral features or other forms of a priori knowledge and detect how methods of generating SPTD can be transferred from the domain of AE to ER. A promising finding is that in both types of systems, in systems from ER that generate behavioral diversity and also in the investigated speciation model, selective pressure is generated towards unpopulated regions of search space. In a simple case study we investigate the practical implications of these findings and point to options for transferring the idea of self-organizing SPTD in AEs to the domain of ER. PMID- 26545164 TI - Cell-Division Behavior in a Heterogeneous Swarm Environment. AB - We present a system of virtual particles that interact using simple kinetic rules. It is known that heterogeneous mixtures of particles can produce particularly interesting behaviors. Here we present a two-species three dimensional swarm in which a behavior emerges that resembles cell division. We show that the dividing behavior exists across a narrow but finite band of parameters and for a wide range of population sizes. When executed in a two dimensional environment the swarm's characteristics and dynamism manifest differently. In further experiments we show that repeated divisions can occur if the system is extended by a biased equilibrium process to control the split of populations. We propose that this repeated division behavior provides a simple model for cell-division mechanisms and is of interest for the formation of morphological structure and to swarm robotics. PMID- 26545165 TI - Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015. SELECTION CRITERIA: Randomized and quasi randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function. PMID- 26545166 TI - Three-Dimensional Porous Aerogel Constructed by g-C3N4 and Graphene Oxide Nanosheets with Excellent Visible-Light Photocatalytic Performance. AB - It is curial to develop a high-efficient, low-cost visible-light responsive photocatalyst for the application in solar energy conversion and environment remediation. Here, a three-dimensional (3D) porous g-C3N4/graphene oxide aerogel (CNGA) has been prepared by the hydrothermal coassembly of two-dimensional g-C3N4 and graphene oxide (GO) nanosheets, in which g-C3N4 acts as an efficient photocatalyst, and GO supports the 3D framework and promotes the electron transfer simultaneously. In CNGA, the highly interconnected porous network renders numerous pathways for rapid mass transport, strong adsorption and multireflection of incident light; meanwhile, the large planar interface between g-C3N4 and GO nanosheets increases the active site and electron transfer rate. Consequently, the methyl orange removal ratio over the CNGA photocatalyst reaches up to 92% within 4 h, which is much higher than that of pure g-C3N4 (12%), 2D hybrid counterpart (30%) and most of representative g-C3N4-based photocatalysts. In addition, the dye is mostly decomposed into CO2 under natural sunlight irradiation, and the catalyst can also be easily recycled from solution. Significantly, when utilized for CO2 photoreduction, the optimized CNGA sample could reduce CO2 into CO with a high yield of 23 mmol g(-1) (within 6 h), exhibiting about 2.3-fold increment compared to pure g-C3N4. The photocatalyst exploited in this study may become an attractive material in many environmental and energy related applications. PMID- 26545168 TI - Surface Charge Transfer Doping of Monolayer Phosphorene via Molecular Adsorption. AB - Monolayer phosphorene has attracted much attention owing to its extraordinary electronic, optical, and structural properties. Rationally tuning the electrical transport characteristics of monolayer phosphorene is essential to its applications in electronic and optoelectronic devices. Herein, we study the electronic transport behaviors of monolayer phosphorene with surface charge transfer doping of electrophilic molecules, including 2,3,5,6-tetrafluoro-7,7,8,8 tetracyanoquinodimethane (F4TCNQ), NO2, and MoO3, using density functional theory combined with the nonequilibrium Green's function formalism. F4TCNQ shows optimal performance in enhancing the p-type conductance of monolayer phosphorene. Static electronic properties indicate that the enhancement is originated from the charge transfer between adsorbed molecule and phosphorene layer. Dynamic transport behaviors demonstrate that additional channels for hole transport in host monolayer phosphorene were generated upon the adsorption of molecule. Our work unveils the great potential of surface charge transfer doping in tuning the electronic properties of monolayer phosphorene and is of significance to its application in high-performance devices. PMID- 26545167 TI - The In Vitro Evaluation of Tigecycline and the In Vivo Evaluation of RPX-978 (0.5% Tigecycline) as an Ocular Antibiotic. AB - PURPOSE: The goals of the current study were to determine the in vitro antibacterial activity of tigecycline against multiple clinically relevant ocular pathogens and to evaluate the in vivo ocular tolerability and efficacy of 0.5% tigecycline in a methicillin-resistant Staphylococcus aureus (MRSA) keratitis model. METHODS: In vitro: Minimum inhibitory concentrations (MICs) were determined for 110 clinical conjunctivitis isolates, 26 keratitis isolates of Pseudomonas aeruginosa, and 10 endophthalmitis isolates each of MRSA, methicillin susceptible S. aureus (MSSA), MR, and MS coagulase-negative Staphylococcus. TOLERABILITY: Six uninfected rabbits were topically treated in both eyes with 0.5% tigecycline, vehicle, or saline every 15 min for 3 h. EFFICACY: Thirty-two rabbits were intrastromally injected with 700 Colony Forming Units (CFU) of MRSA in both eyes and were separated into 4 groups (n = 8): tigecycline 0.5%; vancomycin 5%; saline; and no treatment (euthanized before treatment for baseline CFU). Four hours after MRSA challenge, topical treatment of 1 drop every 15 min for 5 h was initiated. One hour after treatment, the corneas were harvested for CFU. The data were analyzed nonparametrically. RESULTS: In vitro: Tigecycline demonstrated lower MICs than the other tested antibiotics against gram-positive organisms, especially MRSA, while MICs against gram-negative pathogens, including fluoroquinolone-resistant P. aeruginosa, appeared to be in the treatable range with aggressive topical therapy. TOLERABILITY: 0.5% tigecycline was graded as minimally irritating. EFFICACY: 0.5% tigecycline and vancomycin produced similar reductions in CFU and were less than saline (P < 0.05). Tigecycline and vancomycin demonstrated 99.9% reductions compared with baseline CFU. CONCLUSIONS: Tigecycline is a potential candidate for a topical ocular antibiotic. PMID- 26545169 TI - Detection of Vaccinia Virus in Milk: Evidence of a Systemic and Persistent Infection in Experimentally Infected Cows. AB - Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV), which affects lactating cows and milkers. VACV DNA and infectious particles have been detected in milk of naturally infected cows. However, the period and pattern of VACV shedding in milk is unknown, as is whether the presence of VACV in milk is due to a localized or a systemic infection. To address those questions, eight lactating cows were inoculated with VACV in previously scarified teats. The experiment was divided in two phases. In Phase 1, milk samples were collected daily for 33 days, and in Phase 2, four animals from the first phase were immunosuppressed. In both phases, milk was collected with a sterile catheter on even days and by hand milking on odd days. All animals showed typical BV lesions in the inoculated teats. All milk samples were subjected to nested polymerase chain reaction (PCR) and real-time quantitative PCR to detect VACV DNA. PCR-positive samples were subjected to virus isolation. VACV DNA was intermittently detected in milk in both phases and infectious viral particles could be detected only in phase 2, on the 69th, 73rd, 74th, 77th, 79th, and 81st days postinfection. Despite the possibility of propagation of VACV through milk, it is known that milk continues to be drawn and marketed normally during outbreaks of the disease. The detection of both VACV DNA and infectious particles in milk samples draws attention to the potential public health risk associated with the consumption of milk from BV outbreaks. Detection of VACV in the milk from noninfected teats demonstrated that VACV shedding in milk might be related to a systemic infection. Moreover, it was shown that VACV DNA and viral infectious particles could be detected in milk even after healing of the lesions, demonstrating that VACV may cause a persistent infection in cattle. PMID- 26545170 TI - Bacillus cereus Adhesion to Simulated Intestinal Mucus Is Determined by Its Growth on Mucin, Rather Than Intestinal Environmental Parameters. AB - Adhesion of pathogenic bacteria to intestinal mucus, the protective layer of the gastrointestinal epithelium, is often considered a virulence factor. The ability of food-poisoning Bacillus cereus strains to attach to mucus and the factors affecting this interaction have not yet been investigated. Therefore, the role of adhesion in pathogenesis of B. cereus still remains unknown. In the present study, an in vitro assay based on mucin agar was used to simulate adhesion of B. cereus to mucus. Bacterial-associated factors (e.g., strain specificity and microbial competition) known to influence adhesion to different surfaces and a variety of environmental conditions (e.g., pH and oxygen) encountered in the gastrointestinal tract were investigated. The effect of these parameters on B. cereus NVH 0500/00 mucin adhesion was generally limited even in the presence of microbial competition. This suggests that B. cereus NVH 0500/00 is a versatile pathogen. Inoculation of 4 to 5 log colony-forming units (CFU) per milliliter. B. cereus NVH 0500/00 resulted in 5-6 log CFU/mL mucin-associated bacteria after a short incubation period. This indicates that this pathogenic strain could grow in the presence of mucin agar. This growth may potentially mask the effect of the studied conditions. Yet, extensive attachment of B. cereus to mucin is not necessarily a prerequisite for virulence, because other pathogenic strains do not adhere with the same efficiency to mucin. Nevertheless, adhesion may contribute to the disease by providing close contact to nutrient sources, such as mucin, which would not only result in bacterial proliferation, but also in disruption of the protective host mucus surface. PMID- 26545171 TI - Molecular diagnostics: techniques and recommendations for 1p/19q assessment. AB - Several morphology- and polymerase chain reaction (PCR)-based methods for chromosome 1p 19q deletion status assessment are available. Important prerequisites for all molecular techniques concern tissue quality and selection of regions of interest. The most common methods for diagnostic 1p 19q assessment are fluorescence in situ hybridization and PCR-based microsatellite analysis. While the latter requires the use of autologous blood samples, more advanced techniques such as array comparative genomic hybridization, multiplex ligation dependent probe amplification or real-time PCR are independent from autologous DNA samples. However, due to high technical demand and experience required their applicability as diagnostic tests remains to be shown. On the other hand, chromogenic in situ hybridization evolves as attractive alternative to FISH. Herein, the available test methods are reviewed and outlined, their advantages and drawbacks being discussed in detail. PMID- 26545172 TI - A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2. AB - Hypomorphic germline mutations in the PIGA (phosphatidylinositol glycan class A) gene recently were recognized as the cause of a clinically heterogeneous spectrum of X-linked disorders including (i) early onset epileptic encephalopathy with severe muscular hypotonia, dysmorphism, multiple congenital anomalies, and early death ("MCAHS2"), (ii) neurodegenerative encephalopathy with systemic iron overload (ferro-cerebro-cutaneous syndrome, "FCCS"), and (iii) intellectual disability and seizures without dysmorphism. Previous studies showed that the recurrent PIGA germline mutation c.1234C>T (p.Arg412*) leads to a clinical phenotype at the most severe end of the spectrum associated with early infantile lethality. We identified three additional individuals from two unrelated families with the same PIGA mutation. Major clinical findings include early onset intractable epileptic encephalopathy with a burst-suppression pattern on EEG, generalized muscular hypotonia, structural brain abnormalities, macrocephaly and increased birth weight, joint contractures, coarse facial features, widely spaced eyes, a short nose with anteverted nares, gingival overgrowth, a wide mouth, short limbs with short distal phalanges, and a small penis. Based on the phenotypic overlap with Simpson-Golabi-Behmel syndrome type 2 (SGBS2), we hypothesized that both disorders might have the same underlying cause. We were able to confirm the same c.1234C>T (p.Arg412*) mutation in the DNA sample from an affected fetus of the original family affected with SGBS2. We conclude that the recurrent PIGA germline mutation c.1234C>T leads to a recognizable clinical phenotype with a poor prognosis and is the cause of SGBS2. PMID- 26545173 TI - Respiratory variation in aortic blood flow peak velocity to predict fluid responsiveness in mechanically ventilated children: a systematic review and meta analysis. AB - BACKGROUND: Dynamic indices of preload have been shown to better predict fluid responsiveness than static variables in mechanically ventilated adults. In children, dynamic predictors of fluid responsiveness have not yet been extensively studied. AIM: To evaluate the diagnostic accuracy of respiratory variation in aortic blood flow peak velocity (DeltaVPeak) for the prediction of fluid responsiveness in mechanically ventilated children. METHOD: PubMed, Embase, and the Cochrane Database of Systematic Reviews were screened for studies relevant to the use of DeltaVPeak to predict fluid responsiveness in children receiving mechanical ventilation. Clinical trials published as full-text articles in indexed journals without language restriction were included. We calculated the pooled values of sensitivity, specificity, diagnostic odds ratio (DOR), and positive and negative likelihood ratio using a random-effects model. RESULTS: In total, six studies (163 participants) met the inclusion criteria. Data are reported as point estimate with 95% confidence interval. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR of DeltaVPeak to predict fluid responsiveness for the overall population were 92.0% (84.1-96.7), 85.5% (75.6-92.5), 4.89 (2.92-8.18), 0.13 (0.07-0.25), and 50.44 (17.70-143.74), respectively. The area under the summary receiver operating characteristic curve was 0.94. Cutoff values for DeltaVPeak to predict fluid responsiveness varied across studies, ranging from 7% to 20%. CONCLUSION: Our results confirm that the DeltaVPeak is an accurate predictor of fluid responsiveness in children under mechanical ventilation. However, the question of the optimal cutoff value of DeltaVPeak to predict fluid responsiveness remains uncertain, as there are important variations between original publications, and needs to be resolved in further studies. The potential impact of intraoperative cardiac output optimization using goal-directed fluid therapy based on DeltaVPeak on the perioperative outcome in the pediatric population should be subsequently evaluated. PMID- 26545174 TI - A randomized trial comparing multiband mucosectomy and cap-assisted endoscopic resection for endoscopic piecemeal resection of early squamous neoplasia of the esophagus. AB - BACKGROUND AND AIM: Piecemeal endoscopic resection for esophageal high grade intraepithelial neoplasia (HGIN) or early squamous cell carcinoma (ESCC) is usually performed by cap-assisted endoscopic resection. This requires submucosal lifting and multiple snares. Multiband mucosectomy (MBM) uses a modified variceal band ligator without submucosal lifting. In high-risk areas where ESCC is common and endoscopic expertise is limited, MBM may be a better technique. We aimed to compare MBM to the cap-assisted technique for piecemeal endoscopic resection of esophageal ESCCs. METHODS: Patients with mucosal HGIN/ESCC (2 - 6 cm, maximum two thirds of esophageal circumference) were included. Lesions, delineated by 1.25 % Lugol staining, were randomized to MBM or cap-assisted piecemeal resection. Endpoints were procedure time and costs, complete endoscopic resection, adverse events, and absence of HGIN/ESCC at 3-month and 12-month follow-up. RESULTS: Endoscopic resection was performed in 84 patients (59 men, mean age 60) using MBM (n = 42) or the endoscopic resection cap (n = 42). There were no differences in baseline characteristics. Endoscopic complete resection was achieved in all lesions. Procedure time was significantly shorter with MBM (11 vs. 22 minutes, P < 0.0001). One perforation, seen after using the endoscopic resection cap, was treated conservatively. Total costs of disposables were lower for MBM (?200 vs. ?251, P = 0.04). At 3-month and 12-month follow-ups none of the patients had HGIN/ESCC at the resection site. CONCLUSION: Piecemeal endoscopic resection of esophageal ESCC with MBM is faster and cheaper than with the endoscopic resection cap. Both techniques are highly effective and safe. MBM may have significant advantages over the endoscopic resection cap technique, especially in countries where ESCC is extremely common but limited endoscopic expertise and resources exist. (Netherlands trial register: NTR 3246.). PMID- 26545175 TI - Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with colorectal cancer outcome. AB - Single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with the risk and outcome in many cancers. We have identified risk associated D-loop SNPs for colorectal cancer previously, in the present study, we evaluate their prognostic value for postoperative survival of colorectal cancer (CRC). The minor haplotype of nucleotides 16290T and frequent haplotype of nucleotide 16298T in the hypervariable segment 1 (HV1) region of the D-loop were identified for their association with high survival rate of CRC. After adjusted with COX proportional hazard model, the nucleotide site of 16290 was identified as independent predictor for CRC (RR, 0.379; 95% CI, 0.171-0.839; p = 0.017). In conclusion, SNPs in the mtDNA D-Loop were found to be valuable markers for colorectal cancer outcome evaluation. PMID- 26545176 TI - Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery. AB - BACKGROUND: Raised intraocular pressure is a risk factor for glaucoma. One treatment option is glaucoma drainage surgery (trabeculectomy). Antimetabolites are used during surgery to reduce postoperative scarring during wound healing. Two agents in common use are mitomycin C (MMC) and 5-Fluorouracil (5-FU). OBJECTIVES: To assess the effects of MMC compared to 5-FU as an antimetabolite adjunct in trabeculectomy surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 October 2015. SELECTION CRITERIA: We included randomised controlled trials where wound healing had been modified with MMC compared to 5-FU. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and collected data. The primary outcome was failure of a functioning trabeculectomy one year after surgery. Secondary outcomes included mean intraocular pressure at one year. We considered three subgroups: high risk of trabeculectomy failure (people with previous glaucoma surgery, extracapsular cataract surgery, African origin and people with secondary glaucoma or congenital glaucoma); medium risk of trabeculectomy failure (people undergoing trabeculectomy with extracapsular cataract surgery) and low risk of trabeculectomy failure (people who have received no previous surgical eye intervention). MAIN RESULTS: We identified 11 trials that enrolled 687 eyes of 679 participants. The studies were conducted in the United States, Europe, Asia and Africa. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery.We considered one study to be at low risk of bias in all domains, six studies to be at high risk of bias in one or more domains, and the remaining four studies to be at an unclear risk of bias in all domains.The risk of failure of trabeculectomy at one year after surgery was less in those participants who received MMC compared to those who received 5-FU, however the confidence intervals were wide and are compatible with no effect (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.30 to 1.00; studies = 11; I(2) = 40%). There was no evidence for any difference between groups at high and low risk of failure (test for subgroup differences P = 0.69).On average, people treated with MMC had lower intraocular pressure at one year (mean difference (MD) -3.05 mmHg, 95% CI -4.60 to -1.50), but the studies were inconsistent (I(2) = 52%). The size of the effect was greater in the high-risk group (MD -4.18 mmHg, 95% CI -6.73 to -1.64) compared to the low-risk group (MD -1.72 mmHg, 95% CI -3.28 to -0.16), but again the test for interaction was not statistically significant (P = 0.11).Similar proportions of eyes treated with MMC lost 2 or more lines of visual acuity one year after surgery compared to 5-FU, but the confidence intervals were wide (RR 1.05, 95% CI 0.54 to 2.06).Adverse events occurred relatively rarely, and estimates of effect were generally imprecise. There was some evidence for less epitheliopathy in the MMC group (RR 0.23, 95% CI 0.11 to 0.47) and less hyphaema in the MMC group (RR 0.62, 95% CI 0.42 to 0.91).None of the studies reported quality of life.Overall, we graded the quality of the evidence as low largely because of risk of bias in the included studies and imprecision in the estimate of effect. AUTHORS' CONCLUSIONS: We found low-quality evidence that MMC may be more effective in achieving long-term lower intraocular pressure than 5-FU. Further comparative research on MMC and 5-FU is needed to enhance reliability and validity of the results shown in this review. Furthermore, the development of new agents that control postoperative scar tissue formation without side effects would be valuable and is justified by the results of this review. PMID- 26545184 TI - All For One, One For All. PMID- 26545185 TI - Documentation of Coalitions Can Improve the Process, But Will it Lead to Better Outcomes? PMID- 26545186 TI - Perspectives From the Assistant Secretary for Preparedness and Response. PMID- 26545187 TI - Gulf Coast Resilience Coalition: An Evolved Collaborative Built on Shared Disaster Experiences, Response, and Future Preparedness. AB - OBJECTIVE: For close to a decade, the Gulf Coast of the United States has been in almost constant disaster recovery mode, and a number of lessons have been learned concerning disaster recovery and behavioral health. The purpose of this report was to describe the natural development of a Gulf Coast Resilience Coalition (GCRC). METHODS: The GCRC methods began with state-specific recovery goals following Hurricane Katrina in 2005 and transitioned to a shared multistate and multidiscipline coalition. The coalition's effectiveness is demonstrated through continuation, procurement of funding to provide response services, and increased membership to ensure sustainability. RESULTS: The coalition has enhanced response, recovery, and resilience by providing strategic plans for dissemination of knowledge; post-disaster surveillance and services; effective relationships and communication with local, state, and regional partners; disaster response informed by past experience; a network of professionals and community residents; and the ability to improve access to and efficiency of future behavioral health coordination through an organized response. CONCLUSIONS: The GCRC can not only improve readiness and response, but work toward a shared vision of improved overall mental and behavioral health and thus resilience, with beneficial implications for the Gulf South and other communities as well. PMID- 26545188 TI - Physician Emergency Preparedness: A National Poll of Physicians. AB - OBJECTIVE: To provide a more comprehensive view than previously available of US physician preparedness for public health emergencies, this study examined physicians' assessments of their preparedness, training, participation in institutional activities, information practices, and experiences with patient education. Four kinds of public health emergencies were considered: natural disasters, major airborne infections, major foodborne illness outbreaks, and chemical, biological, radiological, nuclear, or explosives (CBRNE) incidents. METHODS: Between October 19, 2011, and January 11, 2012, researchers conducted a national poll among 1603 practicing physicians in a range of specialties in hospital and nonhospital settings. RESULTS: More than one-half of physicians felt prepared to handle a natural disaster, a major outbreak of an airborne infection, or a major foodborne illness outbreak, whereas one-third (34%) felt prepared to handle a CBRNE incident. About one-half of physicians (55%) had participated in training or a conference related to emergencies in the past 2 years. Sizable fractions of physicians were unaware of emergency response tools in their care setting. For example, nearly one-half in hospitals (44%) did not know whether their care setting had an emergency response plan, and less than one-quarter had participated in a drill using such a plan in the past 2 years. Less than one third (31%) of physicians had signed up to receive alerts in the case of future emergencies. One in 10 reported sharing emergency information with patients at least "sometimes." CONCLUSIONS: Significant gaps remain in physician preparedness for public health emergencies, as well as in related training and participation in institutional activities. New efforts, with a focus on possible collaborations between public health institutions and health system leaders combined with effective use of online resources, are needed to bring more physicians on board and to develop relevant and useful key tools. New approaches, including those that rely on different types of care providers, may be needed to enhance patient education regarding emergency preparedness. PMID- 26545189 TI - Medical Surge Capacity in Atlanta-Area Hospitals in Response to Tanker Truck Chemical Releases. AB - OBJECTIVE: We designed and conducted a regional full-scale exercise in 2007 to test the ability of Atlanta-area hospitals and community partners to respond to a terrorist attack involving the coordinated release of 2 dangerous chemicals (toluene diisocyanate and parathion) that were being transported through the area by tanker truck. METHODS: The exercise was designed to facilitate the activation of hospital emergency response plans and to test applicable triage, decontamination, and communications protocols. Plume modeling was conducted by using the Defense Threat Reduction Agency's (DTRA) Hazard Prediction and Assessment Capability (HPAC) V4 program. The scenario went through multiple iterations as exercise planners sought to reduce total injuries to a manageable, but stressful, level for Atlanta's health care infrastructure. RESULTS: Atlanta area hospitals rapidly performed multiple casualty triage and were able to take in a surge of victims from the simulated attack. However, health care facilities were reticent to push the perceived manageable numbers of victims, and scenarios were modified significantly to lower the magnitude of the simulated attack. Additional coordination with community response partners and incident command training is recommended. Security at health care facilities and decontamination of arriving victims are two areas that will require continued review. CONCLUSION: Atlanta-area hospitals participated in an innovative regional exercise that pushed facilities beyond traditional scopes of practice and brought together numerous health care community response partners. Using lessons learned from this exercise coupled with subsequent real-world events and training exercises, participants have significantly enhanced preparedness levels and increased the metropolitan region's medical surge capacity in the case of a multiple casualty disaster. PMID- 26545190 TI - Contributions of Health Care Coalitions to Preparedness and Resilience: Perspectives From Hospital Preparedness Program and Health Care Preparedness Coalitions. AB - OBJECTIVE: The purpose of this article was to describe how the Hospital Preparedness Program (HPP) and other health care coalitions conceptualize and measure progress or success and to identify strategies to improve coalition success and address known barriers to success. METHODS: We conducted a structured literature review and interviews with key leaders from 22 HPPs and other coalitions. Interview transcripts were analyzed by using constant comparative analysis. RESULTS: Five dimensions of coalition success were identified: strong member participation, diversity of members, positive changes in members' capacity to respond to or recover from disaster, sharing of resources among members, and being perceived as a trendsetter. Common barriers to success were also identified (eg, a lack of funding and staff). To address these barriers, coalitions suggested a range of mitigation strategies (eg, establishing formal memoranda of agreement). Both dimensions of and barriers to coalition success varied by coalition type. CONCLUSIONS: Currently, the term health care coalition is a one size-fits-all term. In reality, this umbrella term describes a variety of different configurations, member bodies, and capabilities. The analysis offered a typology to categorize health care coalitions by primary function during a disaster response. Developing a common typology that could be used to specify capabilities or functions of coalitions may be helpful to advancing their development. PMID- 26545191 TI - In Preparation or Response: Examining Health Care Coalitions Amid a Changing Economic and Political Landscape. AB - The Office of the Assistant Secretary for Preparedness and Response within the US Department of Health and Human Services leads the nation in preparing for, responding to, and recovering from the adverse health effects of public health emergencies, in part through formal collaborations between hospitals, health systems, community health centers, public health departments, and community organizations via health care coalitions (HCCs). HCCs endeavor to meet the medical surge demands inherent to disasters and to improve health outcomes before, during, and after public health emergencies. Nevertheless, significant changes in health economics and policy can impact the operations, capabilities, and scope of HCCs. Specifically, hospital consolidation and the Affordable Care Act (ACA) are altering the national health care landscape, as well as the emergency preparedness sector, and are challenging HCCs to adapt to large-scale, industry-wide transformations. This article examines HCCs in the context of the developments of hospital consolidation and the ACA in order to facilitate future discourse regarding the strategy and policy of HCCs amid a changing economic and political landscape. PMID- 26545192 TI - Identifying Indirect Benefits of Federal Health Care Emergency Preparedness Grant Funding to Coalitions: A Content Analysis. AB - OBJECTIVE: This study aimed to identify the indirect benefits of health care preparedness funding as perceived by current and former recipients of the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response's Hospital Preparedness Program. METHODS: This was a qualitative inductive content analysis of telephone interviews conducted with regional stakeholders from several health care coalitions to identify their perceptions of the indirect benefits of preparedness funding. RESULTS: Content analysis of interviewee responses resulted in 2 main categories of indirect benefits of federal health care preparedness funding: (1) dual-use technology and programs and (2) impact of relationships on day-to-day operations. Within the dual-use technology and programs category, 3 subcategories were identified: (1) information systems, (2) clinical technology, and (3) health care operations. Similarly, 3 subcategories relating to the indirect benefits in the impact of relationships on day-to-day operations category were identified: (1) cooperation, (2) information sharing, and (3) sense of community. CONCLUSION: This study identified indirect benefits of federal investment in hospital and health care preparedness in day-to-day operations. Major categories of these benefits included dual-use technology and programs and impact of relationships on day-to day operations. Coalition members placed a high value on these benefits, even though they were not direct outcomes of grant programs. Further research is needed to quantify the economic value of these indirect benefits to more accurately measure the total return on investment from federal grant funding. PMID- 26545193 TI - Transforming Health Care Coalitions From Hospitals to Whole of Community: Lessons Learned From Two Large Health Care Organizations. AB - A health care emergency preparedness coalition (coalition) is a group of health care organizations, public safety agencies, and public health partners that join forces for the common cause of making their communities safer, healthier, and more resilient. Coalitions have been characterized as being focused on hospital systems instead of the health care of the community as a whole. We discuss 2 examples of coalition partners that use a more inclusive approach to planning, response, and recovery. The first is a large health care system spread across 23 states, and the other is a public safety agency in northeast Pennsylvania that took the lead to address the preparedness and response toward a large influx of burn patients and grew to encompass all aspects of community health care. PMID- 26545194 TI - Optimizing Health Care Coalitions: Conceptual Frameworks and a Research Agenda. AB - The US health care system has maintained an objective of preparedness for natural or manmade catastrophic events as part of its larger charge to deliver health services for the American population. In 2002, support for hospital-based preparedness activities was bolstered by the creation of the National Bioterrorism Hospital Preparedness Program, now called the Hospital Preparedness Program, in the US Department of Health and Human Services. Since 2012, this program has promoted linking health care facilities into health care coalitions that build key preparedness and emergency response capabilities. Recognizing that well-functioning health care coalitions can have a positive impact on the health outcomes of the populations they serve, this article informs efforts to optimize health care coalition activity. We first review the landscape of health care coalitions in the United States. Then, using principles from supply chain management and high-reliability organization theory, we present 2 frameworks extending beyond the Office of the Assistant Secretary for Preparedness and Response's current guidance in a way that may help health care coalition leaders gain conceptual insight into how different enterprises achieve similar ends relevant to emergency response. We conclude with a proposed research agenda to advance understanding of how coalitions can contribute to the day-to-day functioning of health care systems and disaster preparedness. PMID- 26545195 TI - The Office of Health Affairs and Our Role in Health Security. PMID- 26545196 TI - The US Department of Veterans Affairs and Sustainable Health Care Coalitions. PMID- 26545197 TI - Preparedness 3.0: Addressing the Future. AB - The last 14 years has taught us that that we are facing a new reality; a reality in which public health emergencies are a common occurrence. Today, we live in a world with dangerous people without state sponsorship who are an enormous threat to our safety; one where emerging and reemerging infectious diseases are waiting to break out; a world where the benefits of globalization in trade, transportation, and social media brings threats to our communities faster and with a greater risk than ever before. Even climate change has entered into the preparedness equation, bringing with it the forces of nature in the form of extreme weather and its complications. PMID- 26545198 TI - MMRS Coalitions: Continuing Their Efforts. PMID- 26545199 TI - Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment. AB - BACKGROUND: Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. METHODS: The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 MUg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. RESULTS: Levels of neutrophil alpha-defensins (human neutrophil peptides 1-3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. CONCLUSION: Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D. PMID- 26545201 TI - Interventions for the treatment of keratocystic odontogenic tumours. AB - BACKGROUND: The keratocystic odontogenic tumours (KCOTs) account for between about 2% and 11% of all jaw cysts and can occur at any age. They are more common in males than females with a male:female ratio of approximately 2:1. Although they are benign, KCOTs are locally very aggressive and have a tendency to recur after treatment. Reported recurrence rates range from 3% to 60%. The traditional method for the treatment of most KCOTs is surgical enucleation. However, due to the lining of the cyst being delicate and the fact that they frequently recur, this method alone is not sufficient. Adjunctive surgical treatment has been proposed in addition to the surgical enucleation, such as removal of the peripheral bone (ostectomy) or resection of the cyst with surrounding bone (en bloc) resection. Other adjunctive treatments proposed are: cryotherapy (freezing) with liquid nitrogen and the use of the fixative Carnoy's solution placed in the cyst cavity after enucleation; both of which attempt to address residual tissue to prevent recurrence. OBJECTIVES: To assess the available evidence comparing the effectiveness of interventions for the treatment of KCOTs. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 17 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 2), MEDLINE via Ovid (1946 to 17 March 2015) and EMBASE via Ovid (1980 to 17 March 2015). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials comparing one modality of intervention with another with or without adjunctive treatment for the treatment of KCOTs. Adults, over the age of 18 with a validated diagnosis of solitary KCOTs arising in the jaw bones of the maxilla or mandible. Patients with known Gorlin syndrome were to be excluded. DATA COLLECTION AND ANALYSIS: Review authors screened trials for inclusion. Full papers were obtained for relevant and potentially relevant trials. If data had been extracted, it would have been synthesised using the fixed-effect model, if substantial clinical diversity were identified between studies we planned to use the random-effects model with studies grouped by action provided there were four or more studies included in the meta-analysis, and we would have explored the heterogeneity between the included studies. MAIN RESULTS: No randomised controlled trials that met the inclusion criteria were identified. AUTHORS' CONCLUSIONS: There are no published randomised controlled trials relevant to this review question, therefore no conclusions could be reached about the effectiveness or otherwise of the interventions considered in this review. There is a need for well designed and conducted randomised controlled trials to evaluate treatments for KCOTs. PMID- 26545200 TI - Dynamics of Transcription Factor Binding Site Evolution. AB - Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ~ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of "pre-sites" or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics. PMID- 26545202 TI - Endoscopic Versus Histological Disease Extent at Presentation of Paediatric Inflammatory Bowel Disease. AB - OBJECTIVES: The Paris classification (PC) of paediatric inflammatory bowel disease categorises disease extent and therefore affects treatment decisions. Histological (microscopic) disease extent is not incorporated, and endoscopic (macroscopic) findings may underrepresent disease extent when compared with histological findings; this study compares disease extent at presentation. METHODS: Data were obtained of patients <17 years of age diagnosed with inflammatory bowel disease from 2010 to 2013 at University Hospital Southampton. Data are presented as percentage of patients undergoing endoscopy. PC was performed alongside a modified PC by histological disease location. RESULTS: A total of 172 patients were identified (median age at diagnosis 13.5 years, 115 boys); Crohn disease (CD) 107, ulcerative colitis (UC) 50, inflammatory bowel disease unclassified (IBDU) 15; 159 had undergone upper gastrointestinal (GI) endoscopy, 163 had undergone lower GI endoscopy. Histological disease was more extensive at all points for CD, UC, and IBDU. CD--endoscopic ileal disease in 49% of patients compared with histological disease in 71.3%. Comparing PC--a 10% increase in L3 disease (ileocolonic), a 24% increase in L3 + L4a disease (ileocolonic plus upper GI), and a 27% increase in all of the upper GI involvement if histological disease extent was used. UC--the most common disease location was the rectum (endoscopic 91.5% vs histological 93.6%) and descending colon (endoscopic 89.4% vs histological 95.7%). Comparing PC--a 19% increase in E4 disease (pancolitis) if histological disease extent was used. CONCLUSIONS: These data confirm that histological disease extent is greater than endoscopic disease extent. This should be considered when the PC is used. Further study is needed to elucidate which classification would better predict disease outcome. PMID- 26545203 TI - Probiotic Administration in Infants With Gastroschisis: A Pilot Randomized Placebo-Controlled Trial. AB - OBJECTIVES: Infants with gastroschisis often require long periods of gastric suctioning and hospitalization. The impact of these interventions on the intestinal microbiota and attempts to alter the microbial community have not been studied. We sought to determine how the intestinal microbiota is influenced by the current treatment of gastroschisis and whether alteration of the intestinal microbiota with a probiotic microbe will influence length of hospitalization. METHODS: We performed a randomized, placebo-controlled pilot study of administration of probiotic Bifidobacterium longum subsp. infantis in 24 infants with gastroschisis. The primary outcome was changes in the fecal microbiota, and the secondary outcome was length of hospital stay. RESULTS: Administration of the probiotic or placebo was well tolerated, even during the period of gastric suctioning. The overall microbial communities were not significantly different between groups, although analysis of the final specimens by family demonstrated higher Bifidobacteriaceae, lower Clostridiaceae, and trends toward lower Enterobacteriaceae, Enterococcaceae, Staphylococcaceae, and Streptococcaceae in the probiotic group. Clinical outcomes, including length of hospital stay, did not differ between groups. CONCLUSIONS: In this pilot study, there was significant in infants with gastroschisis that was partially attenuated by the administration of B longum subsp. infantis. PMID- 26545204 TI - Use of Placebo in Pediatric Inflammatory Bowel Diseases: A Position Paper From ESPGHAN, ECCO, PIBDnet, and the Canadian Children IBD Network. AB - Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an "add-on" to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD. PMID- 26545205 TI - Short and Long-Term Soil Moisture Effects of Liana Removal in a Seasonally Moist Tropical Forest. AB - Lianas (woody vines) are particularly abundant in tropical forests, and their abundance is increasing in the neotropics. Lianas can compete intensely with trees for above- and belowground resources, including water. As tropical forests experience longer and more intense dry seasons, competition for water is likely to intensify. However, we lack an understanding of how liana abundance affects soil moisture and hence competition with trees for water in tropical forests. To address this critical knowledge gap, we conducted a large-scale liana removal experiment in a seasonal tropical moist forest in central Panama. We monitored shallow and deep soil moisture over the course of three years to assess the effects of lianas in eight 0.64 ha removal plots and eight control plots. Liana removal caused short-term effects in surface soils. Surface soils (10 cm depth) in removal plots dried more slowly during dry periods and accumulated water more slowly after rainfall events. These effects disappeared within four months of the removal treatment. In deeper soils (40 cm depth), liana removal resulted in a multi-year trend towards 5-25% higher soil moisture during the dry seasons with the largest significant effects occurring in the dry season of the third year following treatment. Liana removal did not affect surface soil temperature. Multiple and mutually occurring mechanisms may be responsible for the effects of liana removal on soil moisture, including competition with trees, and altered microclimate, and soil structure. These results indicate that lianas influence hydrologic processes, which may affect tree community dynamics and forest carbon cycling. PMID- 26545206 TI - Team dynamics, clinical work satisfaction, and patient care coordination between primary care providers: A mixed methods study. AB - BACKGROUND: Team-based care is essential for delivering high-quality, comprehensive, and coordinated care. Despite considerable research about the effects of team-based care on patient outcomes, few studies have examined how team dynamics relate to provider outcomes. PURPOSE: The aim of this study was to examine relationships among team dynamics, primary care provider (PCP) clinical work satisfaction, and patient care coordination between PCPs in 18 Harvard affiliated primary care practices participating in Harvard's Academic Innovations Collaborative. METHODOLOGY: First, we administered a cross-sectional survey to all 548 PCPs (267 attending clinicians, 281 resident physicians) working at participating practices; 65% responded. We assessed the relationship of team dynamics with PCPs' clinical work satisfaction and perception of patient care coordination between PCPs, respectively, and the potential mediating effect of patient care coordination on the relationship between team dynamics and work satisfaction. In addition, we embedded a qualitative evaluation within the quantitative evaluation to achieve a convergent mixed methods design to help us better understand our findings and illuminate relationships among key variables. FINDINGS: Better team dynamics were positively associated with clinical work satisfaction and quality of patient care coordination between PCPs. Coordination partially mediated the relationship between team dynamics and satisfaction for attending clinicians, suggesting that higher satisfaction depends, in part, on better teamwork, yielding more coordinated patient care. We found no mediating effects for resident physicians. Qualitative results suggest that sources of satisfaction from positive team dynamics for PCPs may be most relevant to attending clinicians. PRACTICE IMPLICATIONS: Improving primary care team dynamics could improve clinical work satisfaction among PCPs and patient care coordination between PCPs. In addition to improving outcomes that directly concern health care providers, efforts to improve aspects of team dynamics may also help resolve critical challenges in workforce planning in primary care. PMID- 26545207 TI - Work-related factors influencing home care nurse intent to remain employed. AB - BACKGROUND: Health care is shifting out of hospitals into community settings. In Ontario, Canada, home care organizations continue to experience challenges recruiting and retaining nurses. However, factors influencing home care nurse retention that can be modified remain largely unexplored. Several groups of factors have been identified as influencing home care nurse intent to remain employed including job characteristics, work structures, relationships and communication, work environment, responses to work, and conditions of employment. PURPOSE: The aim of this study was to test and refine a model that identifies which factors are related to home care nurse intentions to remain employed for the next 5 years with their current home care employer organization. METHODOLOGY/APPROACH: A cross-sectional survey design was implemented to test and refine a hypothesized model of home care nurse intent to remain employed. Logistic regression was used to determine which factors influence home care nurse intent to remain employed. FINDINGS: Home care nurse intent to remain employed for the next 5 years was associated with increasing age, higher nurse-evaluated quality of care, having greater variety of patients, experiencing greater meaningfulness of work, having greater income stability, having greater continuity of client care, experiencing more positive relationships with supervisors, experiencing higher work-life balance, and being more satisfied with salary and benefits. PRACTICE IMPLICATIONS: Home care organizations can promote home care nurse intent to remain employed by (a) ensuring nurses have adequate training and resources to provide quality client care, (b) improving employment conditions to increase income stability and satisfaction with pay and benefits, PMID- 26545208 TI - Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood Brain Barrier. AB - The impermeability of the adult blood-brain barrier (BBB) to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport. A high dose (500 microg/mouse) of clonidine, a strong alpha2 and weak alpha1 agonist, was able to act as monotherapy in the stimulation of P-GUS transport. Neither use of alpha1 plus alpha2 agonists nor the high dose clonidine disrupted the BBB to albumin. In situ brain perfusion and immunohistochemistry studies indicated that adrengerics act on transporters already at the luminal surface of brain endothelial cells. These results show that adrenergic stimulation, including monotherapy with clonidine, could be key for CNS enzyme replacement therapy. PMID- 26545209 TI - Phenotypic- and Genotypic-Resistance Detection for Adaptive Resistance Management in Tetranychus urticae Koch. AB - Rapid resistance detection is necessary for the adaptive management of acaricide resistant populations of Tetranychus urticae. Detection of phenotypic and genotypic resistance was conducted by employing residual contact vial bioassay (RCV) and quantitative sequencing (QS) methods, respectively. RCV was useful for detecting the acaricide resistance levels of T. urticae, particularly for on-site resistance detection; however, it was only applicable for rapid-acting acaricides (12 out of 19 tested acaricides). QS was effective for determining the frequencies of resistance alleles on a population basis, which corresponded to 12 nonsynonymous point mutations associated with target-site resistance to five types of acaricides [organophosphates (monocrotophos, pirimiphos-methyl, dimethoate and chlorpyrifos), pyrethroids (fenpropathrin and bifenthrin), abamectin, bifenazate and etoxazole]. Most field-collected mites exhibited high levels of multiple resistance, as determined by RCV and QS data, suggesting the seriousness of their current acaricide resistance status in rose cultivation areas in Korea. The correlation analyses revealed moderate to high levels of positive relationships between the resistance allele frequencies and the actual resistance levels in only five of the acaricides evaluated, which limits the general application of allele frequency as a direct indicator for estimating actual resistance levels. Nevertheless, the resistance allele frequency data alone allowed for the evaluation of the genetic resistance potential and background of test mite populations. The combined use of RCV and QS provides basic information on resistance levels, which is essential for choosing appropriate acaricides for the management of resistant T. urticae. PMID- 26545211 TI - What about you? PMID- 26545210 TI - Carotid Artery Longitudinal Displacement, Cardiovascular Disease and Risk Factors: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Associations between carotid artery longitudinal displacement, cardiovascular disease risk factors, and events were evaluated in a large, multi ethnic cohort. MATERIALS AND METHODS: A novel, reproducible protocol was developed for measuring right common carotid artery longitudinal displacement using ultrasound speckle-tracking. Total longitudinal displacement was measured in 389 randomly selected participants from the Multi-Ethnic Study of Atherosclerosis that were free of cardiovascular disease at baseline. Univariate analyses and Pearson Correlations were used to define relationships between longitudinal displacement with traditional cardiovascular risk factors and traditional measures of arterial stiffness. Hazard ratios of longitudinal displacement for cardiovascular disease and coronary heart disease events were compared using Cox proportional hazards models. RESULTS: Participants were a mean (standard deviation) 59.0 (8.7) years old, 48% female, 39% White, 26% Black, 22% Hispanic, and 14% Chinese. They had 19 (4.9%) cardiovascular disease and 14 (3.6%) coronary heart disease events over a mean 9.5 years of follow-up. Less longitudinal displacement was associated with Chinese (beta = -0.11, p = 0.02) compared to White race/ethnicity and greater longitudinal displacement was associated with higher carotid intima-media thickness (beta = 0.26, p = 0.004). Longitudinal displacement was not associated with other cardiovascular disease risk factors or markers of arterial stiffness. After adjustment for age and sex, and heart rate, Chinese race/ethnicity (beta = -0.10, p = 0.04) and carotid intima-media thickness (beta = 0.30 p = 0.003) were associated independently with longitudinal displacement. Longitudinal displacement predicted coronary heart disease (Hazard ratio [HR] 3.3, 95% Confidence intervals [CI] 0.96-11.14, p = 0.06) and cardiovascular disease (HR 2.1, 95% CI 0.6-7.3, p = 0.23) events. CONCLUSIONS: Less longitudinal displacement is associated with Chinese ethnicity and greater carotid artery longitudinal displacement is associated with thicker intima-media thickness. Longitudinal displacement may predict adverse coronary heart disease and cardiovascular disease events. PMID- 26545212 TI - Staff-led innovations reduce falls in high-acuity patients. PMID- 26545213 TI - Inverted Nipple With Nipple-Sparing Mastectomy. AB - BACKGROUND: The inverted nipple is a relatively common aesthetic problem seen by plastic surgeons. The etiologies of an inverted nipple include insufficiency of supporting tissues, hypoplasia of the lactiferous ducts, and retraction caused by fibrous bands at the base of the nipple. Many different surgical techniques have been described, either individually or in combination, but none represents a landmark strategy. In our present study, we report our experience of spontaneous improvement immediately after nipple-sparing mastectomy with simple buried interrupted sutures to maintain nipple base in inverted nipple patients. METHODS: We describe our 10 years' experience in using a simple approach to correct inverted nipples after nipple-sparing mastectomy with pedicled transverse rectus abdominis myocutaneous flap reconstruction. Between January 2001 and August 2010, we observed 23 inverted nipples after nipple-sparing mastectomy by using only a buried baseline suture to tighten the base of the nipple. The follow-up period ranged from 3 to 13 years. RESULTS: After nipple-sparing mastectomy with tightening of the base of the nipple, improvements were seen in 18 of the 23 patients. No complications associated with surgery occurred, such as infection, depigmentation, sensory disturbance, or nipple necrosis. CONCLUSIONS: The simple method of baseline suturing that only tightens the nipple base with nipple sparing mastectomy has been used in our center over a 10-year period in patients with breast cancer and an inverted nipple. The retractile duct or fibrous cord was completely cut with nipple-sparing mastectomy, and over 70% of inverted nipples in the patients were improved and maintained with only the tightening of the base of the nipple. Our results show that inverted nipple is caused by tight fibrous band or short duct rather than a lack of subareolar tissue. PMID- 26545214 TI - Bilateral Free Flap Breast Reconstruction After Unilateral Radiation: Comparing Intraoperative Vascular Complications and Postoperative Outcomes in Radiated Versus Nonradiated Breasts. AB - BACKGROUND: Radiation induces vessel damage and impairs tissue healing. To date, only 1 study has examined radiation's impact in autologous breast reconstruction on intraoperative vascular complications and postoperative outcomes. In this follow-up paper, we examine a larger cohort with an improved study design to better control for patient characteristics. METHODS: A database of 1780 patients who underwent autologous breast free flap reconstruction at the University of Pennsylvania's Health System between 2003 and 2014 was searched for patients who underwent bilateral breast reconstruction after unilateral radiation, returning 199 patients for review. These were then analyzed for intraoperative vascular complications as well as postoperative complications. McNemar tests were performed on all variables, comparing between radiated and nonradiated fields. RESULTS: Fields with prior radiation were significantly more likely to have any type of intraoperative vascular complication and need for arterial anastomotic revision compared to fields without prior radiation (14% versus 7%, P = 0.03 and 8% versus 3%, P = 0.04, respectively). Although there was a trend for more frequent arterial thrombosis in radiated compared to nonradiated fields, this was nonsignificant (7% versus 3%, P = 0.08). There was no significant difference in venous thrombosis or need for venous anastomotic revision. Radiated fields were significantly more likely to have postoperative wound infections compared to nonradiated fields (4% versus 0.5%, P = 0.04). There was no difference in other postoperative complications, including postoperative thrombosis, flap loss, mastectomy flap necrosis, fat necrosis, hematoma, seroma, or delayed wound healing. CONCLUSIONS: Intraoperative vascular complications and postoperative wound infections are significantly more likely to occur in autologous breast free flap reconstruction with previous radiation therapy. It is important to plan for and counsel patients that fields with previous radiation are at higher risk for these complications. PMID- 26545216 TI - Fibula Osteoseptocutaneous Flap: Advantages of Beginning the Harvesting From the Posterior Approach. AB - BACKGROUND: The osteoseptocutaneous fibula flap has been widely used for bone and soft tissue reconstruction from its first description in 1975. Nowadays, this flap has become the workhorse flap for head and neck reconstruction because of its suitability for mandible reconstruction. However, the reliability of the skin paddle is still controversial. We described a modified method for the harvesting of an osteoseptocutaneous flap to obtain a more reliable skin paddle while minimizing the donor site morbidity. METHODS: One hundred fifty-one consecutive patients were enrolled in the current study from January 2005 to December 2013. All of them underwent a free osteoseptocutaneous flaps for either head and neck (n = 135) or extremity (n = 16) reconstruction following the posterior approach harvest technique. Demographics data of all the patients were collected: age, sex, defect location, and etiology. The variables included for the statistical analysis were: size of the skin paddle, time of harvesting, reoperation, split skin paddle, and single or double barrel fashion for the inset. The outcomes measured were the flap success rate and the skin paddle survival. RESULTS: The flap success rate was 97.3%. The mean harvesting time was 45 minutes. The mean width and length of the skin paddle was 7.1 +/- 2.6 and 17.41 +/- 4.4 cm, respectively. The reexploration rate was 18.5%, and the salvage was achieved 85.7% of the cases. Partial skin paddle necrosis was found in 13.2% of the cases. The fact of having a reexploration in the postoperative period was the only variable significantly associated with the skin paddle necrosis (P = .001). CONCLUSIONS: According to our experience, the posterior approach for the harvest of the osteoseptocutaneous fibula flap is a safe technique and offers many advantages, such as a better visualization of the perforators, beneficial for chimeric flap elevation, preservation of the muscular fascia in the donor site, and an earlier diagnosis of any anatomical variation. Both the reliable and the versatility of the skin paddle can substantially improve with this approach. PMID- 26545215 TI - Professional Burnout Among Plastic Surgery Residents: Can it be Prevented? Outcomes of a National Survey: Reply. PMID- 26545217 TI - The Lumbar Artery Perforator Flap: 3-Dimensional Anatomical Study and Clinical Applications. AB - BACKGROUND: The lumbar region is a potential donor site for perforator-based rotational or free flaps or as a recipient site for free flaps to obtain coverage for deficits in the sacral region. Because of the lack of consensus regarding the microvascular anatomy of this potential flap site, a robust investigation of the anatomy of this region is required. METHODS: Three-dimensional reconstructions (n = 6) of the microvasculature of the lumbar region were generated using MIMICS software (Materialise, Belgium) for each of the four paired lumbar vessels. Diameter, course, and pedicle length were recorded for all lumbar artery (LA) perforators. Statistical analysis was performed using SigmaStat 4.0 and graphs were generated using GraphPad Prism 6 Software. RESULTS: Perforators arising from the first pair of LAs are reliably detected along the inferior margin of the 12th rib, extending inferiorly and laterally from the midline while perforators arising from the fourth pair of LA perforate the fascia along a horizontal plane connecting the posterior iliac crests. There are significantly more cutaneous perforators arising from the first (L1) and fourth (L4) pairs of LA than from the second (L2) and third (L3) (mean +/- SD: L1, 5.5 +/- 1.2; L2, 1.4 +/- 0.7; L3, 1.3 +/- 0.7; L4, 4.8 +/- 1.0; P < 0.05). The average perforator diameter arising from L1 is greater than those arising from L4 (diameter +/- SD: L1, 1.2 mm +/- 0.2 >L4, 0.8 mm +/- 0.2; P < 0.0001). L1 and L4 perforators have longer pedicle lengths than those arising from L2 and L3 (length +/- SD: L1, 98.2 mm +/- 57.8; L4, 106.1 mm +/- 23.3 >L2, 67.5 mm +/- 27.4; L3, 78.5 mm +/- 30.3; P < 0.05). CONCLUSIONS: Perforators arising from the first and fourth LAs arise in a predictable fashion, have adequate pedicle lengths, and are of suitable diameter to support a perforator flap. We present a case to support the potential use of this flap for microvascular breast reconstruction. PMID- 26545218 TI - Completing a Basic Science Research Year Before the Integrated Plastic Surgery Match. PMID- 26545219 TI - Perforator Propeller Flap for Oncologic Reconstruction of Soft Tissue Defects in Trunk and Extremities. AB - BACKGROUND: Defects after soft tissue sarcoma resection are usually managed by myocutaneous flaps or free flaps. However, harvesting muscle will cause functional morbidities, and some regions lack reliable recipient vessel. Our purpose is to use various perforator propeller flaps for oncologic reconstruction. METHODS: Between 2008 and 2014, 33 perforator propeller flaps were performed in 24 patients to reconstruct the defects after tumor resection in trunk and extremities. Fifteen patients underwent tumor resection previously. Thirteen patients underwent adjuvant radiotherapy or chemotherapy. Flaps based on perforators adjacent to the lesions were raised and rotated in propeller fashion to repair the defects. RESULTS: Twenty-seven flaps were based on perforators of known source vessels, and 6 were harvested in freestyle fashion. The defects were repaired with 2 flaps in 4 patients and 3 flaps in 2 patients. The mean skin paddle dimension was 8.36 cm in width and 20.42 cm in length. The mean degree of flap rotation was 158.79 degrees . Complications include partial necrosis of 6 flaps in 5 cases and venous congestion of 1 flap. In these 6 patients, 3 underwent adjuvant radiotherapy. The donor sites were primarily closed in 21 patients and skin grafted in 3 patients. No functional loss related to flap harvesting was recognized. CONCLUSIONS: The perforator propeller flaps can be used to manage the medium defects in extremities and large defects in torso after soft tissue sarcoma resection. They avoid the sacrifice of the underlying muscle and eliminate the concerns of the unavailability of recipient vessels. The perforator propeller flaps provide flexible options for versatile oncologic reconstruction in trunk and extremities. However, the impact of radiotherapy on the viability of the flaps for local reconstruction needs further investigation. PMID- 26545220 TI - Axillary Lymph Node Dissection Is a Risk Factor for Major Complications After Immediate Breast Reconstruction. AB - BACKGROUND: Complications after immediate breast reconstruction pose a significant challenge to the reconstructive surgeon. Known risk factors include smoking, obesity, age, and adjuvant oncologic therapies. Less is known about the association between axillary lymph node dissection (ALND) and the development of postoperative complications. METHODS: We conducted a retrospective study of all patients who underwent immediate breast reconstruction after mastectomy at our institution over a 10-year period. Our outcome was an occurrence of a major complication within 90 days postoperatively. For each patient, we recorded data on demographics, smoking status, pertinent medical history, reconstruction type, adjuvant chemotherapy and radiation, tumor pathology, and whether an ALND was performed. Odds ratios (OR) were calculated to estimate the risk of a complication if an ALND was performed. RESULTS: One hundred eighty-four women, with 270 surgically treated breasts, were identified as having mastectomy with immediate reconstruction between 2002 and 2012. Mean age was 49.4 years (range, 25-84 years). There were 71 mastectomies with ALND performed, with 22 complications, and 199 mastectomies without ALND, with 20 complications (31% complication rate vs 10%, respectively; OR, 3.84; P < 0.001). When adjusted for reconstruction type, smoking history, obesity, age, presence of invasive disease, chemotherapy, and radiation therapy, the OR for complications was 3.49 (P < 0.01). The most common complication was infection in both groups. CONCLUSIONS: Mastectomy with ALND is associated with a 3-fold increase in risk of major complications in women undergoing immediate breast reconstruction, even after adjustment for known risk factors and confounders. Further studies are warranted to elucidate how ALND leads to these complications and what measures can reduce their occurrence. PMID- 26545221 TI - Geographic Variation in Access to Plastic Surgeons. AB - INTRODUCTION: While recent studies project a national shortage of plastic surgeons, there may currently exist areas within the United States with few plastic surgeons. We conducted this study to describe the current geographic distribution of the plastic surgery workforce across the United States. METHODS: Using the 2013 to 2014 Area Health Resource File, we estimated the number of plastic surgeons at the health service area (HSA) level in 2010 and 2012. The density of plastic surgeons was calculated as a ratio per 100,000 population. The HSAs were grouped by plastic surgeon density, and population characteristics were compared across subgroups. Characteristics of HSAs with increases and decreases in plastic surgeon density were also compared. RESULTS: The final sample included 949 HSAs with a total population of 313,989,954 people. As of 2012, there were an estimated 7600 plastic surgeons, resulting in a national ratio of 2.42 plastic surgeons/100,000 population. However, over 25 million people lived in 468 HSAs (49.3%) without a plastic surgeon, whereas 106 million people lived in 82 HSAs (8.6%) with 3.0 or more/100,000 population. Plastic surgeons were more likely to be distributed in HSAs where a higher percentage of the population was younger than 65 years, female, and residing in urban areas. Between 2010 and 2012, 11 HSAs without a plastic surgeon increased density, whereas 15 HSAs lost all plastic surgeons. CONCLUSIONS: Plastic surgeons are asymmetrically distributed across the United States leaving over 25 million people without geographic access to the specialty. This distribution tends to adversely impact older and rural populations. PMID- 26545222 TI - Exposure to Varying Strain Magnitudes Influences the Conversion of Normal Skin Fibroblasts Into Hypertrophic Scar Cells. AB - Mechanical strain is a key contributor in the pathogenesis of hypertrophic scarring, whose optimal stretch magnitudes to initiate the differentiation of normal skin fibroblasts into aberrant fibroblasts phenotype remains largely unresolved. Influence of varying cyclic strain magnitudes on cultured human normal skin fibroblasts and its transformation into hypertrophic scar fibroblast like phenotype is investigated in this study. Cultured fibroblasts isolated from hypertrophic scar and normal skin tissue were subjected to cyclic mechanical stretching under individual 10%, 15%, and 20% strain magnitudes at a frequency of 0.1 Hz for 24 hours. Stretched normal skin fibroblasts demonstrated significantly increased rates of cell proliferation, and also apparently oriented away nearly perpendicular to the applied stretching direction. Interestingly, the applied 10% strains magnitude resulted in a markedly enhanced cell proliferative ability compared with that of 20% strain magnitude. Parameters involving the mechanotransduction signaling, such as integrin beta1 and P130Cas, were significantly improved at both mRNA and protein levels in the stretched normal skin fibroblasts, which was demonstrated in a negative magnitude-dependent manner. In addition, 10% strains magnitude triggered the highest expression levels of growth factor TGF-beta1 and collagen matrix in stretched normal skin fibroblasts. Collectively, these results indicate that the 10% stretching magnitude, of the 3 strain magnitudes studied, is most effective for triggering the optimal mechanotransduction effects and biological responses inside cultured skin fibroblasts. The demonstrable conversion of normal skin fibroblasts into hypertrophic scar fibroblasts was also observed when 10% stretching magnitude was applied to cultured fibroblasts in vitro. PMID- 26545224 TI - Direct Transversus Abdominis Plane Blocks With Exparel During Abdominoplasty. AB - BACKGROUND: Pain control following abdominoplasty is a major source of concern for the patient and surgeon alike. Pain pumps and opiate medications are currently the frontline therapies. With the following technique, Exparel (liposomal bupivacaine, 72-hour duration of action) has been used for transversus abdominis plane (TAP) blocks under direct visualization during abdominoplasty with the goal of improving pain control during the early and intermediate recovery period. MATERIALS AND METHODS: In this pilot study, 13 consecutive patients were treated with the direct, fascial-splitting technique to reach the TAP plane. Using a spinal needle, 20 mL of liposomal bupivacaine was injected deep to the internal oblique fascia bilaterally under direct vision. Primary and secondary endpoints of total opiate use and patient reported pain scores were assessed. RESULTS: All 13 patients met inclusion criteria as abdominoplasty patients with adequate follow-up data. The average visual analog scale pain score was 2.5 on postoperative day 1 and 1.7 on postoperative day 3. The average total opiate use (the number of 10 mg oxycodone tabs consumed) was 7.5 or 75 mg per patient. CONCLUSIONS: This pilot study demonstrates the safety and efficacy of liposomal bupivacaine TAP blocks under direct vision. Favorable pain control was demonstrated. This represents an exciting opportunity to decrease postoperative pain in the early and intermediate recovery period after abdominoplasty. PMID- 26545225 TI - Do Stem Cells Have an Effect When We Fat Graft? AB - Fat grafting has become a widely accepted modality of soft tissue restoration and has found applications in many areas of aesthetic and reconstructive plastic surgery. Numerous claims have been made regarding the regenerative effects of fat grafting on the recipient bed. The purpose of this paper is to survey the available literature to answer the question of whether fat grafting has a positive effect on the surrounding tissues. It has been convincingly demonstrated that fat grafts contain viable adipose-derived stem cells (ASCs). The fate of these cells is determined by the microenvironment of the recipient bed, but animal studies have shown that a large fraction of ASCs survive engraftment. Numerous clinical studies have demonstrated the positive effects of fat grafting on recipient tissues. Improvement in validated scar scores as well as scar stiffness measurements have been documented after fat grafting of burn scars. Fat grafting has also been convincingly demonstrated to improve the quality of irradiated tissues, as measured by validated clinical scales and staged histology. It is ultimately unclear whether ASCs are responsible for these effects, but the circumstantial evidence is weighty. Fat grafting is effective for volumizing and improving skin quality in the setting of radiation, burns, and other scars. The observed effects are likely due to ASCs, but the evidence does not support the routine use of ASC-enriched fat grafts. PMID- 26545226 TI - The Need for Core Outcome Reporting in Autologous Fat Grafting for Breast Reconstruction. AB - INTRODUCTION: There is growing interest in autologous fat grafting (AFG) for breast reconstruction. This systematic review examines the range of outcomes used across studies of AFG, their definitions and whether there is a need for a core outcome set to aid reporting. METHODS: Following the protocol of our systematic review, a search of 20 databases (1986 to March 2014) returned 35 studies which met the inclusion criteria. These were assessed independently by two authors. Disagreements were resolved by consensus. RESULTS: Of the 35 studies, 27 (77%) were case series, 5 (14.3%) were cohort studies, and 3 (8.6%) were case reports. A total of 51 different outcomes were reported. These studies each reported a median of five separate outcomes (range, 2-14), of which a median of 3 outcomes were defined (range, 0-14). A median of 2 outcomes per paper were prespecified in the study methods (range, 0-12) and a median of only 2 outcomes per paper (range, 0-12) were both defined and prespecified. The most commonly reported outcome in studies of AFG was that of "operative details," reported by 26 studies, and eight different outcome definitions were used. "Cancer recurrence" was reported by 20 studies, with the use of 10 different outcome definitions. Overall, there was a poor proportion of defined and prespecified outcomes that employed a wide range of different outcome definitions. In addition only 14/35 studies stated the number of patients lost to follow-up. CONCLUSIONS: There is a need for a core outcomes set for AFG to the breast to minimise outcome and reporting bias and aid evidence synthesis. Our future research will focus in this direction, titled VOGUE or Valid Outcomes for the Grafting of AUtologous Fat to the BrEast study. We invite all those interested to get in touch with the lead author. PMID- 26545227 TI - Effectiveness of a Novel Augmented Reality-Based Navigation System in Treatment of Orbital Hypertelorism. AB - BACKGROUND: Augmented reality (AR) technology can superimpose the virtual image generated by computer onto the real operating field to present an integral image to enhance surgical safety. The purpose of our study is to develop a novel AR based navigation system for craniofacial surgery. We focus on orbital hypertelorism correction, because the surgery requires high preciseness and is considered tough even for senior craniofacial surgeon. METHODS: Twelve patients with orbital hypertelorism were selected. The preoperative computed tomography data were imported into 3-dimensional platform for preoperational design. The position and orientation of virtual information and real world were adjusted by image registration process. The AR toolkits were used to realize the integral image. Afterward, computed tomography was also performed after operation for comparing the difference between preoperational plan and actual operational outcome. RESULTS: Our AR-based navigation system was successfully used in these patients, directly displaying 3-dimensional navigational information onto the surgical field. They all achieved a better appearance by the guidance of navigation image. The difference in interdacryon distance and the dacryon point of each side appear no significant (P > 0.05) between preoperational plan and actual surgical outcome. CONCLUSIONS: This study reports on an effective visualized approach for guiding orbital hypertelorism correction. Our AR-based navigation system may lay a foundation for craniofacial surgery navigation. The AR technology could be considered as a helpful tool for precise osteotomy in craniofacial surgery. PMID- 26545228 TI - Correcting the Alar Base Retraction in Crooked Nose by Dissection of Levator Alaque Nasi Muscle. AB - BACKGROUND: Nasal base retraction results from cephalic malposition of the alar base in the vertical plane causing disharmonies in the alar base. In literature, there are some excisional procedures to correct this deformity, but it may result to nostril distortion, stenosis, or upper lip elevation. Here, a new technique is reported for the correction of nasal base retraction in crooked nose by manipulating the levator labii alaeque nasi muscle. METHODS: Sixteen patients, 6 women and 10 men ranging in age from 21 to 42 years, who have alar retraction with crooked nose, were operated, with a follow-up period of 12 months. Preoperative and postoperative frontal, profile, base, and oblique base views in a standard manner were taken and analyzed with Image software. RESULTS: Comparison of preoperative and postoperative photographs demonstrated that nasal base retractions were corrected in all cases without distortion and recurrence. Nasal obstruction was reduced after surgery, and self-evaluation of nasal patency scores significantly increased in all patients (P < 0.001). Functional and aesthetic outcomes were satisfactory for surgeons and the patients. CONCLUSIONS: Careful analysis to identify the deformity and proper selection of the technique will ensure a pleasing outcome. The new techniques presented for the correction of nasal base retraction and prevention of the recurrence of the dorsal deviation will help rhinoplasty surgeons obtain pleasing outcomes. PMID- 26545229 TI - Modified Full Thickness Graded Blepharotomy for Upper Eyelid Retraction Associated With Thyroid Eye Disease in East Asians. AB - PURPOSE: To evaluate the functional and cosmetic outcomes of modified full thickness graded blepharotomy when used for East Asian patients with upper eyelid retraction of thyroid eye disease (TED). METHOD: Medical records of each patient who underwent modified full-thickness blepharotomy at Korea University Guro Hospitals from January 2009 to February 2014 to correct upper eyelid retraction resulting from TED were retrospectively reviewed. RESULTS: Modified full thickness graded blepharotomies were performed on 22 eyelids of 18 patients. The most common preoperative upper eyelid retraction-associated symptom was asymmetry of the upper eyelid (14 patients, 77.7%) followed by discomfort (10 patients, 55.5%), photophobia (5 patients, 27.7%), and epiphora (4 patients, 22.2%). Most preoperative symptoms improved after blepharotomy (Table 1). Preoperatively, upper eyelid retraction (MRD1; midpupil marginal reflex distance) ranged from 2.3 mm to 6.8 mm (mean, 5.23 +/- 0.89) in 22 lids; postoperatively, lid retraction significantly decreased to 3.26 +/- 1.23 mm (P = 0.03 by independent t test) (Table 2). Lid retraction was divided into 3 groups according to severity; a severe group (5 eyelids, 27.7%), a moderate group (14 eyelids, 63.6%), and a mild group (3 eyelids, 13.6%). The MRD1 improved regardless of severity (P = 0.03 in the severe group, P = 0.02 in the moderate group, and P = 0.04 in the mild group by independent t test). The MRD1 improvement did not differ significantly among groups (P = 0.08 by Pearson chi t test). At 6 months postoperatively, the midpupil marginal reflex distance was the perfect height in 13 of 22 lids (59.0%), with a mean reduction of 3 mm, whereas 7 of 22 eyelids (31.8%) were at acceptable height and 2 eyelids (9.0%) showed failure. Overall, 18 eyelids (90.9%) exhibited objectively satisfactory results (perfect or acceptable) at 6 months after surgery (Table 3). CONCLUSIONS: Modified graded full thickness eyelid blepharotomy is a reliable and safe method for upper eyelid lengthening for East Asian patients with upper eyelid retraction of TED that offers excellent functional and cosmetic results. PMID- 26545230 TI - John B. Stanbury (May 15, 1915-July 6, 2015). PMID- 26545232 TI - Comparative Study of Non-Enveloped Icosahedral Viruses Size. AB - Now, as before, transmission electron microscopy (TEM) is a widely used technique for the determination of virions size. In some studies, dynamic light scattering (DLS) has also been applied for this purpose. Data obtained by different authors and using different methods could vary significantly. The process of TEM sample preparation involves drying on the substrate, which can cause virions to undergo morphology changes. Therefore, other techniques should be used for measurements of virions size in liquid, (i.e. under conditions closer to native). DLS and nanoparticle tracking analysis (NTA) provide supplementary data about the virions hydrodynamic diameter and aggregation state in liquid. In contrast to DLS, NTA data have a higher resolution and also are less sensitive to minor admixtures. In the present work, the size of non-enveloped icosahedral viruses of different nature was analyzed by TEM, DLS and NTA: the viruses used were the encephalomyocarditis virus (animal virus), and cauliflower mosaic virus, brome mosaic virus and bean mild mosaic virus (plant viruses). The same, freshly purified, samples of each virus were used for analysis using the different techniques. The results were compared with earlier published data and description databases. DLS data about the hydrodynamic diameter of bean mild mosaic virus, and NTA data for all examined viruses, were obtained for the first time. For all virus samples, the values of size obtained by TEM were less than virions sizes determined by DLS and NTA. The contribution of the electrical double layer (EDL) in virions hydrodynamic diameter was evaluated. DLS and NTA data adjusted for EDL thickness were in better agreement with TEM results. PMID- 26545233 TI - Frequency-Dependent Modulation of Regional Synchrony in the Human Brain by Eyes Open and Eyes Closed Resting-States. AB - The eyes-open (EO) and eyes-closed (EC) states have differential effects on BOLD fMRI signal dynamics, affecting both the BOLD oscillation frequency of a single voxel and the regional homogeneity (ReHo) of several neighboring voxels. To explore how the two resting-states modulate the local synchrony through different frequency bands, we decomposed the time series of each voxel into several components that fell into distinct frequency bands. The ReHo in each of the bands was calculated and compared between the EO and EC conditions. The cross-voxel correlations between the mean frequency and the overall ReHo of each voxel's original BOLD series in different brain areas were also calculated and compared between the two states. Compared with the EC state, ReHo decreased with EO in a wide frequency band of 0.01-0.25 Hz in the bilateral thalamus, sensorimotor network, and superior temporal gyrus, while ReHo increased significantly in the band of 0-0.01 Hz in the primary visual cortex, and in a higher frequency band of 0.02-0.1 Hz in the higher order visual areas. The cross-voxel correlations between the frequency and overall ReHo were negative in all the brain areas but varied from region to region. These correlations were stronger with EO in the visual network and the default mode network. Our results suggested that different frequency bands of ReHo showed different sensitivity to the modulation of EO-EC states. The better spatial consistency between the frequency and overall ReHo maps indicated that the brain might adopt a stricter frequency-dependent configuration with EO than with EC. PMID- 26545235 TI - Diorganyl dichalcogenides as useful synthons for colloidal semiconductor nanocrystals. AB - The ability to synthesize colloidal semiconductor nanocrystals in a well controlled manner (i.e., with fine control over size, shape, size dispersion, and composition) has been mastered over the past 15 years. Much of this success stems from careful studies of precursor conversion and nanocrystal growth with respect to phosphine chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals. Despite the high level of success that has been achieved with phosphine chalcogenides, there has been a longstanding interest in exploring alternate chalcogenide precursors because of issues associated with phosphine chalcogenide cost, purity, toxicity, etc. This has resulted in a large body of literature on the use of sulfur and selenium dissolved in octadecene or amines, thio- and selenoureas, and silyl chalcogenides as alternate chalcogenide precursors for metal chalcogenide nanocrystal synthesis. In this Account, emerging work on the use of diorganyl dichalcogenides (R-E-E-R, where E = S, Se, or Te and R = alkyl, allyl, benzyl, or aryl) as alternate chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals is summarized. Among the benefits of these dichalcogenide synthons are the following: (i) they represent the first and only common precursor type that can function as chalcogen transfer reagents for each of the group VI elements (i.e., to make metal oxide, metal sulfide, metal selenide, and metal telluride nanocrystals); (ii) they possess relatively weak E-E bonds that can be readily cleaved under mild thermolytic or photolytic conditions; and (iii) the organic substituents can be tuned to affect the reactivity. These combined attributes have allowed dichalcogenide precursors to be employed for a wide range of metal chalcogenide nanocrystal syntheses, including those for In2S3, SnxGe1-xSe, SnTe, Cu2-xSySe1-y, ZnSe, CdS, CdSe, MoSe2, WSe2, BiSe, and CuFeS2. Interestingly, a number of metastable phases of compositionally complex semiconductors can be kinetically accessed through syntheses utilizing dichalcogenide precursors, likely as a result of their ability to convert at relatively low temperatures. These include the hexagonal wurtzite phases of CuInS2, CuInSe2, Cu2ZnSn(S1-xSex)4, and Cu2SnSe3 nanocrystals. The discovery of crystal phases on the nanoscale that do not exist in their bulk analogues is a developing area of nanocrystal chemistry, and dichalcogenides are proving to be a useful synthetic tool in this regard. The most recent application of dichalcogenide synthons for semiconductor nanocrystals is their use as precursors for surface ligands. While there is a rich history of using thiol ligands for semiconductor nanocrystals, the analogous selenol and tellurol ligands have not been studied, likely because of their oxidative instability. Dichalcogenides have proven useful in this regard, as they can be reduced in situ with diphenylphosphine to give the corresponding selenol or tellurol ligand that binds to the nanocrystal surface. This chemistry has been applied to the in situ synthesis and ligand binding of selenols to PbSe nanocrystals and both selenols and tellurols to CdSe nanocrystals. These initial studies have allowed the photophysics of these nanocrystal-ligand constructs to be investigated; in both cases, it appears that the selenol and tellurol ligands act as hole traps that quench the photoluminescence of the semiconductor nanocrystals. PMID- 26545234 TI - On the Adjacency Matrix of RyR2 Cluster Structures. AB - In the heart, electrical stimulation of cardiac myocytes increases the open probability of sarcolemmal voltage-sensitive Ca2+ channels and flux of Ca2+ into the cells. This increases Ca2+ binding to ligand-gated channels known as ryanodine receptors (RyR2). Their openings cause cell-wide release of Ca2+, which in turn causes muscle contraction and the generation of the mechanical force required to pump blood. In resting myocytes, RyR2s can also open spontaneously giving rise to spatially-confined Ca2+ release events known as "sparks." RyR2s are organized in a lattice to form clusters in the junctional sarcoplasmic reticulum membrane. Our recent work has shown that the spatial arrangement of RyR2s within clusters strongly influences the frequency of Ca2+ sparks. We showed that the probability of a Ca2+ spark occurring when a single RyR2 in the cluster opens spontaneously can be predicted from the precise spatial arrangements of the RyR2s. Thus, "function" follows from "structure." This probability is related to the maximum eigenvalue (lambda1) of the adjacency matrix of the RyR2 cluster lattice. In this work, we develop a theoretical framework for understanding this relationship. We present a stochastic contact network model of the Ca2+ spark initiation process. We show that lambda1 determines a stability threshold for the formation of Ca2+ sparks in terms of the RyR2 gating transition rates. We recapitulate these results by applying the model to realistic RyR2 cluster structures informed by super-resolution stimulated emission depletion (STED) microscopy. Eigendecomposition of the linearized mean-field contact network model reveals functional subdomains within RyR2 clusters with distinct sensitivities to Ca2+. This work provides novel perspectives on the cardiac Ca2+ release process and a general method for inferring the functional properties of transmembrane receptor clusters from their structure. PMID- 26545236 TI - Balanced bilinguals favor lexical processing in their opaque language and conversion system in their shallow language. AB - Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280 ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography. PMID- 26545237 TI - Mitochondrial Transcription Factor A (TFAM) Binds to RNA Containing 4-Way Junctions and Mitochondrial tRNA. AB - Mitochondrial DNA (mtDNA) is maintained within nucleoprotein complexes known as nucleoids. These structures are highly condensed by the DNA packaging protein, mitochondrial Transcription Factor A (TFAM). Nucleoids also include RNA, RNA:DNA hybrids, and are associated with proteins involved with RNA processing and mitochondrial ribosome biogenesis. Here we characterize the ability of TFAM to bind various RNA containing substrates in order to determine their role in TFAM distribution and function within the nucleoid. We find that TFAM binds to RNA containing 4-way junctions but does not bind appreciably to RNA hairpins, internal loops, or linear RNA:DNA hybrids. Therefore the RNA within nucleoids largely excludes TFAM, and its distribution is not grossly altered with removal of RNA. Within the cell, TFAM binds to mitochondrial tRNAs, consistent with our RNA 4-way junction data. Kinetic binding assays and RNase-insensitive TFAM distribution indicate that DNA remains the preferred substrate within the nucleoid. However, TFAM binds to tRNA with nanomolar affinity and these complexes are not rare. TFAM-immunoprecipitated tRNAs have processed ends, suggesting that binding is not specific to RNA precursors. The amount of each immunoprecipitated tRNA is not well correlated with tRNA celluar abundance, indicating unequal TFAM binding preferences. TFAM-mt-tRNA interaction suggests potentially new functions for this protein. PMID- 26545238 TI - Increased Difficulties in Managing Stairs in Visually Impaired Older Adults: A Community-Based Survey. AB - PURPOSE: Managing stairs is a challenging aspect of daily activities of living for older people. We assessed whether older adults with visual impairment (VI) have greater difficulties of managing stairs in daily lives. METHODS: The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years and older in rural China. Visual acuity (VA) was measured in both eyes using a retro-illuminated Snellen chart with tumbling-E optotypes. VI (including blindness) was defined as presenting VA of worse than 20/60 in either eye. Having any difficulties in managing stairs was self-reported based on a question drawn from the Barthel Index. Information on participants' socioeconomic status, lifestyle-related factors, diseases histories and medication intake was collected using a questionnaire. RESULTS: The Barthel Index, Activities of Daily Living questionnaire was completed by 4597 (99.7%) participants including 2218 men and 2379 women. The age of the participants ranged from 60 to 93 years with a mean of 67.6 +/- 6.3 years. In age and gender adjusted models, adults with VI had a higher likelihood of having difficulties in managing stairs (odds ratio [OR] = 2.7; 95% confidence interval [CI] 2.0, 3.7) compared with those without. The association of VI with the likelihood of having difficulties in managing stairs was stronger in older adults who lived alone (OR = 3.2; 95%CI 1.8, 4.5) compared with those who lived with other family members (OR = 2.0; 95%CI 1.3, 4.3). Compared with hypertension, diabetes, obesity and cognitive dysfunction, VI had the greatest impact on people's abilities of managing stairs. CONCLUSION: VI was associated with an increased likelihood of having difficulties in managing stairs, especially in those who lived alone. However, whether the finding could be extrapolated to other populations warrants further studies as different environmental exposures such as illumination and types of stairs may alter the association observed in this study. PMID- 26545239 TI - Competence and Quality in Real-Life Decision Making. AB - What distinguishes a competent decision maker and how should the issue of decision quality be approached in a real-life context? These questions were explored in three studies. In Study 1, using a web-based questionnaire and targeting a community sample, we investigated the relationships between objective and subjective indicators of real-life decision-making success. In Study 2 and 3, targeting two different samples of professionals, we explored if the prevalent cognitively oriented definition of decision-making competence could be beneficially expanded by adding aspects of competence in terms of social skills and time-approach. The predictive power for each of these three aspects of decision-making competence was explored for different indicators of real-life decision-making success. Overall, our results suggest that research on decision making competence would benefit by expanding the definition of competence, by including decision-related abilities in terms of social skills and time-approach. Finally, the results also indicate that individual differences in real-life decision-making success profitably can be approached and measured by different criteria. PMID- 26545241 TI - Correction: Identification of Candidate Coral Pathogens on White Band Disease Infected Staghorn Coral. PMID- 26545240 TI - Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women's Health Initiative. AB - Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women's Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1 3) or moderate/severe POP (grades 2-3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relation to POP (grade 0 vs 1-3; grade 0 vs 2-3) adjusting for age at diagnosis, body mass index, parity, and genetic ancestry. There were 1274 controls and 1427 cases of any POP and 317 cases of moderate/severe POP. Although none of the analyses reached genome-wide significance (p<5x10-8), we noted variants in several loci that met p<10-6. In race-specific analysis of grade 0 vs 2-3, intronic SNPs in the CPE gene (rs28573326, OR:2.14; 95% CI 1.62-2.83; p = 1.0x10-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96-4.48, p = 2.6x10-7) were associated with POP in HPs. Inverse variance fixed-effect meta analysis of the race-specific results showed suggestive signals for SNPs in the DPP6 gene (rs11243354, OR:1.36; p = 4.2x10-7) in the grade 0 vs 1-3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6x10-7) and SHC3 (rs2209875, OR:0.60; p = 9.3x10-7) in the grade 0 vs 2-3 analyses. While we did not identify genome-wide significant findings, we document several SNPs reaching suggestive statistical significance. Further interrogation of POP in larger minority samples is warranted. PMID- 26545242 TI - Population Dynamics of Owned, Free-Roaming Dogs: Implications for Rabies Control. AB - BACKGROUND: Rabies is a serious yet neglected public health threat in resource limited communities in Africa, where the virus is maintained in populations of owned, free-roaming domestic dogs. Rabies elimination can be achieved through the mass vaccination of dogs, but maintaining the critical threshold of vaccination coverage for herd immunity in these populations is hampered by their rapid turnover. Knowledge of the population dynamics of free-roaming dog populations can inform effective planning and implementation of mass dog vaccination campaigns to control rabies. METHODOLOGY/PRINCIPAL FINDINGS: We implemented a health and demographic surveillance system in dogs that monitored the entire owned dog population within a defined geographic area in a community in Mpumalanga Province, South Africa. We quantified demographic rates over a 24 month period, from 1st January 2012 through 1st January 2014, and assessed their implications for rabies control by simulating the decline in vaccination coverage over time. During this period, the population declined by 10%. Annual population growth rates were +18.6% in 2012 and -24.5% in 2013. Crude annual birth rates (per 1,000 dog-years of observation) were 451 in 2012 and 313 in 2013. Crude annual death rates were 406 in 2012 and 568 in 2013. Females suffered a significantly higher mortality rate in 2013 than males (mortality rate ratio [MRR] = 1.54, 95% CI = 1.28-1.85). In the age class 0-3 months, the mortality rate of dogs vaccinated against rabies was significantly lower than that of unvaccinated dogs (2012: MRR = 0.11, 95% CI = 0.05-0.21; 2013: MRR = 0.31, 95% CI = 0.11-0.69). The results of the simulation showed that achieving a 70% vaccination coverage during annual campaigns would maintain coverage above the critical threshold for at least 12 months. CONCLUSIONS AND SIGNIFICANCE: Our findings provide an evidence base for the World Health Organization's empirically derived target of 70% vaccination coverage during annual campaigns. Achieving this will be effective even in highly dynamic populations with extremely high growth rates and rapid turnover. This increases confidence in the feasibility of dog rabies elimination in Africa through mass vaccination. PMID- 26545244 TI - Cognitive Reflection and the Diligent Worker: An Experimental Study of Millennials. AB - Recent studies have shown that despite crucially needing the creative talent of millennials (people born after 1980) organizations have been reluctant to hire young workers because of their supposed lack of diligence. We propose to help resolve this dilemma by studying the determinants of task performance and shirking behaviors of millennials in a laboratory work environment. We find that cognitive ability is a good predictor of task performance in line with previous literature. In contrast with previous research, personality traits do not consistently predict either task performance or shirking behaviors. Shirking behaviors, as measured by the time participants spent browsing the internet for non-work purposes (Cyberloafing), were only explained by the performance on the Cognitive Reflection Test (CRT). This finding echoes recent research in cognitive psychology according to which conventional measures of cognitive ability only assess a narrow concept of rational thinking (the algorithmic mind) that fails to capture individuals' capacity to reflect and control their impulses. Our findings suggest that hiring diligent millennials relies on the use of novel cognitive measures such as CRT in lieu of standard personality and intelligence tests. PMID- 26545243 TI - Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus. AB - Cancer immunotherapy has been revolutionised by the use monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcgammaRs). The low-affinity FcgammaR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcgammaR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A 158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcgammaR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcgammaR genetics in predicting response to antibody therapeutics. PMID- 26545245 TI - Evaluation of Argos Telemetry Accuracy in the High-Arctic and Implications for the Estimation of Home-Range Size. AB - Animal tracking through Argos satellite telemetry has enormous potential to test hypotheses in animal behavior, evolutionary ecology, or conservation biology. Yet the applicability of this technique cannot be fully assessed because no clear picture exists as to the conditions influencing the accuracy of Argos locations. Latitude, type of environment, and transmitter movement are among the main candidate factors affecting accuracy. A posteriori data filtering can remove "bad" locations, but again testing is still needed to refine filters. First, we evaluate experimentally the accuracy of Argos locations in a polar terrestrial environment (Nunavut, Canada), with both static and mobile transmitters transported by humans and coupled to GPS transmitters. We report static errors among the lowest published. However, the 68th error percentiles of mobile transmitters were 1.7 to 3.8 times greater than those of static transmitters. Second, we test how different filtering methods influence the quality of Argos location datasets. Accuracy of location datasets was best improved when filtering in locations of the best classes (LC3 and 2), while the Douglas Argos filter and a homemade speed filter yielded similar performance while retaining more locations. All filters effectively reduced the 68th error percentiles. Finally, we assess how location error impacted, at six spatial scales, two common estimators of home-range size (a proxy of animal space use behavior synthetizing movements), the minimum convex polygon and the fixed kernel estimator. Location error led to a sometimes dramatic overestimation of home-range size, especially at very local scales. We conclude that Argos telemetry is appropriate to study medium-size terrestrial animals in polar environments, but recommend that location errors are always measured and evaluated against research hypotheses, and that data are always filtered before analysis. How movement speed of transmitters affects location error needs additional research. PMID- 26545246 TI - Delayed school start times and adolescent sleep: A systematic review of the experimental evidence. AB - Many schools have instituted later morning start times to improve sleep, academic, and other outcomes in response to the mismatch between youth circadian rhythms and early morning start times. However, there has been no systematic synthesis of the evidence on the effects of this practice. To examine the impact of delayed school start time on students' sleep, health, and academic outcomes, electronic databases were systematically searched and data were extracted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six studies satisfied selection criteria and used pre-post, no control (n = 3), randomized controlled trial (n = 2), and quasi-experimental (n = 1) designs. School start times were delayed 25-60 min, and correspondingly, total sleep time increased from 25 to 77 min per weeknight. Some studies revealed reduced daytime sleepiness, depression, caffeine use, tardiness to class, and trouble staying awake. Overall, the evidence supports recent non-experimental study findings and calls for policy that advocates for delayed school start time to improve sleep. This presents a potential long-term solution to chronic sleep restriction during adolescence. However, there is a need for rigorous randomized study designs and reporting of consistent outcomes, including objective sleep measures and consistent measures of health and academic performance. PMID- 26545247 TI - Modelling changes in sleep timing and duration across the lifespan: Changes in circadian rhythmicity or sleep homeostasis? AB - Sleep changes across the lifespan, with a delay in sleep timing and a reduction in slow wave sleep seen in adolescence, followed by further reductions in slow wave sleep but a gradual drift to earlier timing during healthy ageing. The mechanisms underlying changes in sleep timing are unclear: are they primarily related to changes in circadian processes, or to a reduction in the neural activity dependent build up of homeostatic sleep pressure during wake, or both? We review existing studies of age-related changes to sleep and explore how mathematical models can explain observed changes. Model simulations show that typical changes in sleep timing and duration, from adolesence to old age, can be understood in two ways: either as a consequence of a simultaneous reduction in the amplitude of the circadian wake-propensity rhythm and the neural activity dependent build-up of homeostatic sleep pressure during wake; or as a consequence of reduced homeostatic sleep pressure alone. A reduction in the homeostatic pressure also explains greater vulnerability of sleep to disruption and reduced daytime sleep-propensity in healthy ageing. This review highlights the important role of sleep homeostasis in sleep timing. It shows that the same phenotypic response may have multiple underlying causes, and identifies aspects of sleep to target to correct delayed sleep in adolescents and advanced sleep in later life. PMID- 26545249 TI - Hymen reconstruction as pragmatic empowerment? Results of a qualitative study from Tunisia. AB - Hymen reconstruction surgery (HR), while ethically controversial, is now available in many countries. Little clinical evidence and hardly any surgical standards support the intervention. Nearly as scarce is social science research exploring women's motivations for the intervention, and health care professionals' justifications for its provision. In order to better understand decision-making processes, we conducted semi-structured interviews in metropolitan Tunis, in 2009, with six women seeking the procedure, four friends who supported such women, four physicians who perform the operation, and one midwife. Health care professionals and patient companions expressed moral ambivalence about HR: although they could comprehend the individual situation of the women, they expressed concern that availability of the procedure might further entrench the patriarchal norms that compel the motivation for seeking HR in the first place. Some women seeking HR shared this concern, but felt it was not outweighed by their personal aims, which were to marry and become mothers, or to overcome past violent sexual experiences. The women felt HR to be uniquely helpful in achieving these aims; all made pragmatic decisions about their bodies in a social environment dominated by patriarchal norms. The link between HR and pervasive gender injustice, including the credible threat of serious social and physical harm to women perceived to have failed to uphold the norm of virginity before marriage, raises questions about health care professionals' responsibility while facing requests for HR. Meaningful regulatory guidance must acknowledge that these genuine harms are at stake; it must do so, however, without resorting to moral double standards. We recommend a reframing of HR as a temporary resource for some women making pragmatic choices in a context of structural gender injustice. We reconfirm the importance of factual sexual and reproductive education, most importantly to counter distorted beliefs that conflate an "intact hymen" with virginity. PMID- 26545248 TI - Caffeine-Induced Premature Chromosome Condensation Results in the Apoptosis-Like Programmed Cell Death in Root Meristems of Vicia faba. AB - We have demonstrated that the activation of apoptosis-like programmed cell death (AL-PCD) was a secondary result of caffeine (CF) induced premature chromosome condensation (PCC) in hydroxyurea-synchronized Vicia faba root meristem cells. Initiation of the apoptotic-like cell degradation pathway seemed to be the result of DNA damage generated by treatment with hydroxyurea (HU) [double-stranded breaks (DSBs) mostly] and co-treatment with HU/CF [single-stranded breaks (SSBs) mainly]. A single chromosome comet assay was successfully used to study different types of DNA damage (neutral variant-DSBs versus alkaline-DSBs or SSBs). The immunocytochemical detection of H2AXS139Ph and PARP-2 were used as markers for DSBs and SSBs, respectively. Acridine orange and ethidium bromide (AO/EB) were applied for quantitative immunofluorescence measurements of dead, dying and living cells. Apoptotic-type DNA fragmentation and positive TUNEL reaction finally proved that CF triggers AL-PCD in stressed V. faba root meristem cells. In addition, the results obtained under transmission electron microscopy (TEM) further revealed apoptotic-like features at the ultrastructural level of PCC-type cells: (i) extensive vacuolization; (ii) abnormal chromatin condensation, its marginalization and concomitant degradation; (iii) formation of autophagy-like vesicles (iv) protoplast shrinkage (v) fragmentation of cell nuclei and (vi) extensive degeneration of the cells. The results obtained have been discussed with respect to the vacuolar/autolytic type of plant-specific AL-PCD. PMID- 26545250 TI - Nutrition, Frailty, Cognitive Frailty and Prevention of Disabilities with Aging. AB - Older adults can be categorized into three subgroups to better design and develop personalized interventions: the disabled (those needing assistance in the accomplishment of basic activities of daily living), the 'frail' (those presenting limitations and impairments in the absence of disability) and the 'robust' (those without frailty or disability). However, despite evidence linking frailty with a poor outcome, frailty is not implemented clinically in most countries. Since many people are not identified as frail, their treatment is frequently inappropriate in health care settings. Assessing the frail and prefrail older adults can no longer be delayed, we should rather act preventively before the irreversible disabling cascade is in place. Clinical characteristics of frailty such as weakness, low energy, slow walking speed, low physical activity and weight loss underline the links between nutrition and frailty. Physical frailty is also associated with cognitive frailty. We need to better understand cognitive frailty, a syndrome which must be differentiated from Alzheimer's disease. At the Gerontopole frailty clinics, we have found that almost 40% of the patients referred to our center by their primary care physicians to evaluate frailty had significant weight loss in the past 3 months, 83.9% of patients presented slow gait speed, 53.8% a sedentary lifestyle and 57.7% poor muscle strength. Moreover, 43% had a Mini-Nutritional Assessment less than 23.5 and 9% less than 17, which reflects protein-energy undernutrition. More than 60% had some cognitive impairment associated with physical frailty. PMID- 26545251 TI - Melamine Induces Oxidative Stress in Mouse Ovary. AB - Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were analyzed, and the concentration of malondialdehyde (MDA) were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway. PMID- 26545252 TI - The Biological Value of Protein. AB - The biological value of a protein extends beyond its amino-acid composition and digestibility, and can be influenced by additional factors in a tissue-specific manner. In healthy individuals, the slow appearance of dietary amino acids in the portal vein and subsequently in the systemic circulation in response to bolus protein ingestion improves nitrogen retention and decreases urea production. This is promoted by slow absorption when only protein is ingested (e.g. casein). When a full meal is ingested, whey achieves slightly better nitrogen retention than soy or casein, which is very likely achieved by its high content of essential amino acids (especially leucine). Elderly people exhibit 'anabolic resistance' implying that more protein is required to reach maximal rates of muscle protein synthesis compared to young individuals. Protein utilization in inflammatory or traumatic conditions increases substantially in the splanchnic tissues containing most of the immune system, and in wounds and growing tissues. This happens especially in the elderly, which often suffer from chronic inflammatory activity due to disease, physical inactivity and/or the aging process itself. Consequently, the proportion of protein absorbed in the gut and utilized for muscle protein synthesis decreases in these situations. This compromises dietary protein-induced stimulation of muscle protein synthesis and ultimately results in increased requirements of protein (~1.2 g/kg body weight/day) to limit gradual muscle loss with age. To optimally preserve muscle mass, physical exercise is required. Exercise has both direct effects on muscle mass and health, and indirect effects by increasing the utilization of dietary protein (especially whey) to enhance rates of muscle protein synthesis. PMID- 26545253 TI - A Novel Canine Model of Acute Vertebral Artery Occlusion. AB - BACKGROUND: The extended time window and theoretic reduction in hemorrhage make mechanical strategies an attractive approach for the treatment of patients with ischemic stroke. However, a limited availability of suitable animal models of cerebrovascular thrombosis has hampered the study of novel endovascular interventions. The aim of the present study was to develop a new technique for site-specific placement of a thrombus in a canine model that would allow for the evaluation of mechanical thrombectomy and clot retrieval methods and the visualization of thrombus dislocation or fragmentation during angiographic manipulation. METHODS: Angiography and embolization with a preformed thrombus were performed in 12 canines. Under fluoroscopic guidance, an embolism protection device (EPD) was anchored to the middle segment of the left vertebral artery (VA) via the left femoral arterial sheath. A preformed radiopaque clot was injected through the guide catheter into the left VA, via the contralateral femoral artery, proximal to the EPD. After 15 min of occlusion, the EPD was removed and persistent occlusion of the VA was documented angiographically. RESULTS: Angiography performed during the observation period confirmed the persistence of VA occlusion in each case, and displacement of the radiopaque clots did not occur during the 3-hour observation period. The technique allowed selective embolization of targeted vessels without thrombus fragmentation. CONCLUSION: This study demonstrates, for the first time, a canine model of post-circulation embolism induced by autologous blood clot placement. This model can be rapidly formed and easily operated, and the site of thrombosis can be readily controlled. PMID- 26545254 TI - Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System. AB - Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR? G758 to RRSR?R758), which introduces a putative furin-like cleavage (?) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies. PMID- 26545255 TI - Macrophage Receptor with Collagenous Structure (MARCO) Is Processed by either Macropinocytosis or Endocytosis-Autophagy Pathway. AB - The Macrophage Receptor with COllagenous structure (MARCO) protein is a plasma membrane receptor for un-opsonized or environmental particles on phagocytic cells. Here, we show that MARCO was internalized either by ruffling of plasma membrane followed by macropinocytosis or by endocytosis followed by fusion with autophagosome in CHO-K1 cells stably transfected with GFP-MARCO. The macropinocytic process generated large vesicles when the plasma membrane subsided. The endocytosis/autophagosome (amphisome) generated small fluorescent puncta which were visible in the presence of glutamine, chloroquine, bafilomycin, ammonia, and other amines. The small puncta, but not the large vesicles, co localized with LC3B and lysosomes. The LC3-II/LC3-I ratio increased in the presence of glutamine, ammonia, and chloroquine in various cells. The small puncta trafficked between the peri-nuclear region and the distal ends of cells back and forth at rates of up to 2-3 MUm/sec; tubulin, but not actin, regulated the trafficking of the small puncta. Besides phagocytosis MARCO, an adhesive plasma membrane receptor, may play a role in incorporation of various extracellular materials into the cell via both macropinocytic and endocytic pathways. PMID- 26545256 TI - Diagnostic Value of T-Cell Interferon-gamma Release Assays on Cerebrospinal Fluid for Tuberculous Meningitis. AB - Diagnosis of tuberculous meningitis (TBM) remains a challenge. This study aimed to evaluate the performance of T-SPOT.TB test on cerebrospinal fluid mononuclear cells (CSFMCs) for suspected TBM patients. 43 consecutive patients with suspected TBM were enrolled in the study from June 2011 to September 2014. T-SPOT.TB was performed on both CSFMCs and peripheral blood mononuclear cells (PBMCs). The final diagnosis of TBM was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on CSFMCs and PBMCs were analyzed. Of the 43 patients, 12 (27.9%) were finally diagnosed with TBM, 28 (65.1%) with non-TBM, and 3 (7.0%) with indeterminate diagnoses. Of 40 cases with definite diagnoses, the sensitivity and specificity were 92.0% and 96.0% for T-SPOT.TB on CSFMCs, and 83.0% and 82.0% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on CSFMCs were 85.0% and 96.0%, respectively. The PPV and NPV were 67.0% and 92.0% for T-SPOT.TB on PBMCs. The difference of T SPOT.TB between CSFMCs and PBMCs was not significant so far as sensitivity, specificity, PPV, and NPV were concerned (P>0.05 for each). However, T-SPOT.TB on CSFMC and CSFMC: PBMC in TBM cases seemed higher than that in non-TBM cases. Our study further showed that T-SPOT.TB on CSFMCs might be a rapid and accurate diagnostic test for TBM. CSFMC: PBMC T-SPOT.TB ratio might be useful for the early diagnosis of TBM. PMID- 26545257 TI - Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies. AB - BACKGROUND: Numerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with "for and against" debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD. METHODS: Systematic review of register-based studies on long-term BZD use published in 1994-2014. RESULTS: Fourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as "long-term" varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13-36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31-64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found. CONCLUSIONS: Long-term BZD use is common and a clinical reality. Uniform definitions for "long term", which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use. PMID- 26545258 TI - The End of the One-Child Policy: Lasting Implications for China. PMID- 26545259 TI - Optic Disc - Fovea Angle: The Beijing Eye Study 2011. AB - PURPOSE: To determine the optic disc-fovea angle (defined as angle between the horizontal and the line between the optic disc center and the fovea) and to assess its relationships with ocular and systemic parameters. METHODS: The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals. A detailed ophthalmic examination was carried out. Using fundus photographs, we measured the disc-fovea angle. RESULTS: Readable fundus photographs were available for 6043 eyes of 3052 (88.0%) individuals with a mean age of 63.6+/-9.3 years (range: 50-91 years) and a mean axial length of 23.2+/ 1.0 mm (range: 18.96-28.87 mm). Mean disc-fovea angle was 7.76 +/- 3.63 degrees (median: 7.65 degrees ; range: -6.3 degrees to 28.9 degrees ). The mean inter eye difference was 4.01 +/- 2.94 degrees (median: 3.49 degrees ; range: 0.00 22.3 degrees ). In multivariate analysis, larger disc-fovea angle was associated (regression coefficient r2: 0.08) with older age (P = 0.009; standardized regression coefficient beta: 0.05), thinner RNFL in the nasal superior sector (P<0.001; beta: -0.17), superior sector (P<0.001; beta: -0.10) and temporal superior sector (P<0.001; beta: -0.11) and thicker RNFL in the inferior sector (P<001; beta: 0.13), nasal inferior sector (P<001; beta: 0.13) and nasal sector (P = 0.007; beta: 0.06), higher prevalence of retinal vein occlusion (P = 0.02; beta: 0.04), and with larger cylindrical refractive error (P = 0.04; beta: 0.04). CONCLUSIONS: The optic disc-fovea angle markedly influences the regional distribution of the RNFL thickness pattern. The disc-fovea angle may routinely be taken into account in the morphological glaucoma diagnosis and in the assessment of structure-function relationship in optic nerve diseases. Future studies may address potential associations between a larger disc-fovea angle and retinal vein occlusions and between the disc-fovea angle and the neuroretinal rim shape. PMID- 26545260 TI - Contributions of the surgeon Nikolai Korotkov (1874-1920) to the management of extremity vascular injury. AB - The Russian military surgeon Nikolai Korotkov is known worldwide, mainly among internists and cardiovascular specialists, as the discoverer of the auscultatory method of measuring arterial blood pressure in 1905. This article reveals him as one of the first military vascular surgeons to carefully investigate, analyze, and register cases of vascular injury during his voluntarily trips to the Russian Far East in 1900 to 1901 and the Russo-Japanese War of 1904 to 1905. Examining 44 patients with extremity arterial and arterial-venous pseudoaneurysms following war-related injury, he routinely performed a measure termed the "arterial pressure index" using "Korotkov sounds." This pioneering approach to assessing extremity perfusion was the precursor to the modern-day ankle-brachial and injured extremity indices, and it initiated the quantitative assessment of the compensatory ability of the vascular system to restore circulation following axial artery ligation. Because of high thrombosis rates following direct vessel repair during his day, he proposed use of pharmacologic substances such as digitalis and amyl nitrite to improve extremity perfusion. As evidence of his innovative nature, Korotkov even proposed the use of "oxygenated nutrient solutions" in the future to improve extremity circulation. More than 100 years after his work, as continuous wave Doppler ultrasound, contrast angiography, and computed tomography are ubiquitous as diagnostic tools, the practice of surgery would be well served to recall Korotkov's foundational work and the rule of thumb for any physician: examine the patient. PMID- 26545261 TI - Novel triazolyl-functionalized chitosan derivatives with different chain lengths of aliphatic alcohol substituent: Design, synthesis, and antifungal activity. AB - Chemical modification of chitosan is increasingly studied for its potential of providing new application for chitosan. Here, we modify chitosan at its primary hydroxyl via 'click chemistry', and a group of novel water soluble chitosan derivatives with substituted 1,2,3-triazolyl group were designed and synthesized. Aliphatic alcohols with different lengths were used as functional dendrons to improve the antifungal activity of chitosan derivatives. Meanwhile, their antifungal activity against two kinds of phytopathogens was estimated by hypha measurement in vitro. All the chitosan derivatives exhibited excellent activity against tested fungi. It is found that the antifungal activity of chitosan derivatives against the tested fungi increases with augment in the chain length of straight aliphatic alcohols. And the hydrophobic moiety (alkyl) at the periphery of the synthesized chitosan derivatives tends to affect their antifungal activity. PMID- 26545262 TI - Substrate-binding specificity of chitinase and chitosanase as revealed by active site architecture analysis. AB - Chitinases and chitosanases, referred to as chitinolytic enzymes, are two important categories of glycoside hydrolases (GH) that play a key role in degrading chitin and chitosan, two naturally abundant polysaccharides. Here, we investigate the active site architecture of the major chitosanase (GH8, GH46) and chitinase families (GH18, GH19). Both charged (Glu, His, Arg, Asp) and aromatic amino acids (Tyr, Trp, Phe) are observed with higher frequency within chitinolytic active sites as compared to elsewhere in the enzyme structure, indicating significant roles related to enzyme function. Hydrogen bonds between chitinolytic enzymes and the substrate C2 functional groups, i.e. amino groups and N-acetyl groups, drive substrate recognition, while non-specific CH-pi interactions between aromatic residues and substrate mainly contribute to tighter binding and enhanced processivity evident in GH8 and GH18 enzymes. For different families of chitinolytic enzymes, the number, type, and position of substrate atoms bound in the active site vary, resulting in different substrate-binding specificities. The data presented here explain the synergistic action of multiple enzyme families at a molecular level and provide a more reasonable method for functional annotation, which can be further applied toward the practical engineering of chitinases and chitosanases. PMID- 26545263 TI - Social stress in early adolescents' daily lives: Associations with affect and loneliness. AB - Adolescence is characterized by increased social stress due to changes in interpersonal relationships, but little is known about daily experiences of social stress. The aim of the present study was to examine daily life predictors of increases in social stress, how these increases affected adolescents' mood, and whether loneliness moderated these relations. The Experience Sampling Method was used to measure positive and negative affect and increases in social stress in 278 early adolescents from the Netherlands. Results showed that adolescents were most likely to experience increases in social stress when they were with classmates, during week days, and in the morning. Lonely adolescents showed higher increases in social stress and responded more negatively to increases in social stress, compared to non-lonely adolescents. PMID- 26545264 TI - Statistical issues in trials of preexposure prophylaxis. AB - PURPOSE OF REVIEW: We discuss selected statistical issues in the design and analysis of preexposure prophylaxis (PrEP) trials. The general principles may inform thinking for other interventions in HIV prevention. RECENT FINDINGS: To date, four different designs have been used to determine the effectiveness of PrEP: randomized, double-blind, placebo-controlled; randomized, open-label, immediate or delayed access; nonrandomized comparison of HIV incidence according to the level of drug detected; comparison of the observed HIV incidence to the expected rate using historical control data. Open-label trials of PrEP, which assess public health effectiveness, complement the placebo-controlled trials which established the biological efficacy of TDF/FTC. Future trials of PrEP will be highly challenging to design since a no PrEP group is difficult to justify and the natural control regimen, TDF/FTC, is highly efficacious. SUMMARY: Standard statistical paradigms for noninferiority trials should be reconsidered for evaluating alternative PrEP regimens. PMID- 26545265 TI - What does preexposure prophylaxis mean for treatment; what does treatment mean for preexposure prophylaxis? AB - PURPOSE OF REVIEW: Both preexposure prophylaxis (PrEP) and treatment as prevention (TaP) have shown promise in contributing to HIV prevention, in models, observational cohorts and in real-world intervention studies. They share similarities, in that they use the same drugs, toxicity markers and may be focused on the same key populations. How to implement PrEP is still the source of much debate; effective coverage with TaP, with recent data on the positive impact of treatment at high CD4 counts, is still an ongoing challenge. RECENT FINDINGS: Treatment has demonstrated individual benefit even at CD4 counts above 350 cells/MUl; PrEP has shown the effectiveness in real-world use. SUMMARY: This article discusses the intersection of the two interventions, some programmatic misconceptions and complexities, and argues that PrEP is a nuanced and useful adjunct to HIV programmes. PrEP can be rolled out in a way that complements treatment, possibly even within primary health clinics, and may be required for the many people in whom TaP currently fails. PrEP will need constant adaptation so as to maintain programmatic and cost-effectiveness, as the epidemiology of HIV changes with TaP rollout and expansion as CD4 restrictions are lifted. Finally, the article also argues that so-called ethical concerns around competing resources are relatively easily resolved. PMID- 26545266 TI - Constructing the cascade of HIV care: methods for measurement. AB - PURPOSE OF REVIEW: Although the concept of the HIV treatment cascade has reached nearly ubiquitous acceptance in international HIV policy and research, methods for estimating it vary drastically. These variations become increasingly important as the focus of the HIV response shifts from emergency response to long term outcomes and financial and organizational sustainability. We review the history of the cascade and the current literature and develop the first comprehensive typology of cascade scope and methods. RECENT FINDINGS: We define the cascade scope in terms of both breadth (range from first to final event) and depth (given breadth, number of cascade stages that analyzed). We distinguish cascade measurement according to four dimensions: denominator-denominator linkage (data used for cascade construction are linked at the individual level across stages); denominator-numerator linkage (data are linked at the individual level within each stage); single vs. multiple populations from which data sources are drawn; and longitudinal vs. cross-sectional design. SUMMARY: Everything else equal, we would prefer broader and deeper cascades, denominator-denominator linkage, denominator-numerator linkage, single population, and longitudinal data over their respective alternatives. Increased investments in population-based cohorts and data linkage are required to complement clinical cohorts for 'broad' longitudinal cascade analyses. PMID- 26545267 TI - Healing with love. PMID- 26545268 TI - The Academy for Sports Dentistry and the Academy of General Dentistry: a winning team. PMID- 26545269 TI - Additive occlusal equilibration. PMID- 26545270 TI - Do current sports nutrition guidelines conflict with good oral health? AB - For optimal athletic performance, an athlete requires good oral health to reduce the risk of oral pain, inflammation, and infection and thereby minimize the use of analgesics and antimicrobial agents. Increased intake, frequency, and dental contact time of carbohydrate-rich foods, sports nutrition products, and acidic carbohydrate-containing sports and energy drinks may contribute to risks of dental erosion, caries, and inflammatory periodontal conditions in the athlete, especially when he or she also exhibits dehydration and poor oral hygiene habits. Examining the athlete before he or she begins participating in a sport allows the dental care provider to determine the patient's existing oral health, hygiene, and susceptibility to risk factors for erosion, caries, and inflammatory periodontal disease. This oral profile, in conjunction with the individual athlete's dietary needs, can be used to establish a treatment and preventive program, including oral health education. Good oral hygiene practices and application of topical fluoride, especially via fluoridated toothpastes and topical fluoride varnishes, must be available to the athlete. Rinsing with water or a neutral beverage after exposure to carbohydrates or acidic sports nutrition products may reduce carbohydrate contact time and bring oral pH levels back to neutral more quickly, reducing the risk of caries and erosion. Finally, the dentist should encourage the athlete to consult with an experienced sports dietitian to ensure that principles of sports nutrition are being appropriately applied for the type, frequency, and duration of exercise in consideration of the individual's oral health needs. PMID- 26545271 TI - Traumatic injuries to athletes. AB - The timeliness of treatment after dental trauma is crucial to successful tooth preservation. This article focuses on the emergency treatment of common forms of dental trauma in athletes, both at the site of the injury and at the dental office. When dental injuries happen to young patients, saving the tooth is an absolute priority, because few long-term replacement solutions can be performed in a growing child. Preserving pulpal vitality of immature teeth is essential to allow continued root development. PMID- 26545272 TI - Effects of various mouthpieces on respiratory physiology during steady-state exercise in college-aged subjects. AB - Protective mouthpieces have been used in a variety of sports to decrease the risk of orofacial injury. There are limited data to suggest that mouthpiece use during exercise may also provide an ergogenic effect. The aim of the present study was to investigate the effects of 3 different mouthpiece designs-boil-and-bite (BB) mouthpiece, ethylene vinyl acetate (EVA) custom mandibular mouthpiece, and polypropylene (Poly) custom mandibular mouthpiece-on respiratory physiology parameters and compare them with results of a no-mouthpiece (NM) condition. Sixteen college-aged, recreationally fit subjects ran for 10 minutes in 4 separate trials; mouthpiece conditions were randomly assigned to each trial for all subjects. Respiratory and cardiorespiratory measures, including oxygen uptake, carbon dioxide exhalation, ventilation, heart rate, tidal volume, and respiratory rate (RR), were assessed throughout testing. A repeated-measures analysis of variance indicated that RR was significantly lower (P = 0.04) in the BB mouthpiece condition (27.92 breaths per minute [BPM]) than in the NM condition (30.63 BPM). In paired t tests between conditions, the RR demonstrated in the BB condition (27.92 BPM) was significantly lower (P = 0.04) than that of each other condition (NM, 30.63 BPM; EVA, 29.92 BPM; and Poly, 29.92 BPM). The outcomes of the present study demonstrate that the use of the BB mouthpiece decreased RR during exercise. The differences cited between conditions may be attributed to the design of the mouthpiece and its mandibular placement as well as the activity of the genioglossus muscle. However, future studies should assess these parameters to determine the plausibility of these theories. PMID- 26545273 TI - Mandatory mouthguard rules for high school athletes in the United States. AB - High school athletes seem particularly predisposed to dental injury, but athletic mouthguards have an excellent track record of success in reducing the severity and incidence of dental injuries in sports. Therefore, it has been suggested that mouthguards be made mandatory for high school athletes who participate in sports with risk of injury. The National Federation of State High School Associations currently recommends that mouthguards be mandated for high school football, lacrosse, ice hockey, and field hockey players as well as for wrestlers who are wearing orthodontic appliances. Different states have tried to mandate additional sports with varying degrees of success. This article summarizes the process that leads to rule changes for high school athletes at the national level and discusses the history of 4 states--Minnesota, Maine, New Hampshire, and Massachusetts--that have tried to mandate mouthguards for different sports. Common complaints that lead to the cessation of mouthguard rules, such as speech considerations, breathing ability, and cleanliness, are discussed. PMID- 26545274 TI - Effect of clenching with a mouthguard on head acceleration during heading of a soccer ball. AB - Concussions are acceleration-deceleration injuries that occur when biomechanical forces are transmitted to the cerebral tissues. By limiting acceleration of the head, enhanced cervical muscle activity derived from clenching with a mouthguard (MG) may reduce the incidence or severity of concussions following impact. The purpose of this study was to investigate the effect of voluntary clenching with a proper MG on acceleration of the head during "heading" of a soccer ball. Eleven male high school soccer players (mean age, 16.8 years) participated in the study. Each player was given a customized MG. An automated soccer machine was used to project the ball at the participants at a constant speed. The participants headed the ball under 3 different oral conditions: drill 1, heading freely performed without instruction and without the MG; drill 2, heading performed as the subject was instructed to clench the masseter muscles tightly while not wearing the MG; drill 3, heading performed as the subject was instructed to clench tightly while wearing the MG. Each participant repeated each drill 5 times. Linear acceleration of the head was measured with a 3-axis accelerometer. Activity of the masseter and sternocleidomastoid muscles was measured by wireless electromyography. Weak masseter and sternocleidomastoid muscle activity was observed during drill 1. After the soccer players had been instructed to clench their masseter muscles (drills 2 and 3), statistically significant decreases in head acceleration and increases in masseter and sternocleidomastoid muscle activity were observed (P < 0.05; paired t test). The effect was stronger when the players wore the MG. Dentists should encourage soccer players to habitually clench while wearing a proper mouthguard to strengthen cervical muscle resistance as a way to mitigate the damage caused by heading. PMID- 26545275 TI - Effects of mouthguards on vertical dimension, muscle activation, and athlete preference: a prospective cross-sectional study. AB - Mandibular repositioning and subsequent neuromuscular signaling are proposed mechanisms of action for commercial mouthguards marketed for performance enhancement. A prospective cross-sectional study of 24 healthy adult weightlifters with normal occlusal relationships was designed to determine whether 2 self-fit performance mouthguards; a custom-fabricated, bilaterally balanced, dual-laminated mouthguard; and no mouthguard (control) differed in their effects on vertical dimension, muscle activation, and user preference during a 75% maximum power clean lift. Each subject was tested for each of the mouthguard categories: Power Balance POWERUP, Under Armour ArmourBite, custom, and no mouthguard. Interocclusal distance was measured at baseline and with each mouthguard. Mean and peak activity of the anterior temporalis, masseter, sternocleidomastoid, and cervical paraspinal muscles was measured during sitting and during a 75% maximum power clean lift. A mouthguard preference questionnaire was completed. Analyses were conducted to determine whether interocclusal distance differed among mouthguard type and to examine the effect of mouthguard type on mean and peak muscle activation during the clean lift. Interocclusal distance was affected by mouthguard type (P = 0.01). Mean and peak activity of the anterior temporalis and masseter muscles and mean activity of the sternocleidomastoid muscle differed among mouthguards (P < 0.05). Mouthguard type did not influence muscle activation of the cervical paraspinal muscle group. Overall, the Power Balance mouthguard produced more muscle activity. Participants preferred custom mouthguards nearly 2:1 over self-fit performance mouthguards (P = 0.05). Participants perceived that they were stronger and were less encumbered when using a custom mouthguard during submaximum power clean lifts. PMID- 26545276 TI - Splinting rationale and contemporary treatment options for luxated and avulsed permanent teeth. AB - The continued growth in athletic participation among children and adults has increased the potential incidence of sports-related dental injuries. Regardless of preventive measures, damage and injury to the oral cavity can occur during participation in sports. Luxations, root fractures, bony fractures, and avulsions involving 1 or more teeth are a possibility. Many of these injuries require specific protocols for splinting of the traumatized tooth or teeth to allow the best possible outcomes. This article identifies luxation and avulsion injuries, explains the rationale for splinting, reviews guidelines for splint duration, and discusses contemporary material options available to stabilize affected permanent dentition. PMID- 26545277 TI - A survey of attitudes, behaviors, and needs of team dentists. AB - Elite athletes strive to attain superior levels of health and fitness; however, many have high levels of oral disease. Oral screenings detect disease and need for treatment and identify opportunities for preventive interventions. Many dentists volunteer their time with sports organizations, but their scope of practice and needs are unknown. The purposes of this study were to gather baseline data about attitudes, practice behaviors, and needs of team dentists and to assess dental services provided, including the type and frequency of oral screenings conducted on athletes and any associated barriers to those screenings. This descriptive study utilized an original online survey, comprising 37 supplied response questions, that was pilot tested for face and content validity. All dentist members of the Academy for Sports Dentistry were invited to participate (n = 491), and 150 responded, yielding a 31% response rate. The survey format allowed respondents to skip questions, and some respondents chose not to answer some questions. Quantitative data collected included level of athletes, league affiliation, scope of services provided, and types of oral screening performed. Dentists' attitudes regarding athletes' treatment and preventive needs, practice behaviors, and self-identified needs were assessed. Descriptive statistics were used to analyze the data. Results revealed that 116 of 146 respondents (80%) had a league affiliation. Among 112 dentists who reported providing services to athletes, the most frequently provided services were emergency treatment (96%), mouthguards (96%), restorative treatment (79%), oral hygiene instruction (63%), prophylaxis (61%), periodontal charting (61%), and dental charting (60%). Most team dentists (80%; n = 90/112) performed oral screenings for the athletes. Among 87 respondents who performed screenings and reported the type of screening they provided, 36 (41%) screened all athletes prior to the season and then provided individualized follow-up examinations as needed. The most commonly cited barrier to screenings was lack of awareness of the importance of oral health. Additional education for athletes, coaches, owners, schools, and leagues is needed to increase the value placed on oral health. PMID- 26545278 TI - Effect of prolonged air drying on the bond strength of adhesive systems to dentin. AB - This in vitro study evaluated the effect of air-drying time on degree of solvent evaporation (DE), dentin microtensile bond strength (uTBS), and degree of conversion (DC) of 5 adhesive systems: Adper Single Bond 2, XP Bond, Prime & Bond 2.1, OptiBond Solo, and Adper Easy One. For DE testing, 20 uL of each material was submitted to measurements in a digital balance after an air stream of 3, 5, 10, 20, 30, or 60 seconds; the weight loss was computed and converted to a percentage (DE). For uTBS testing, 50 sound human molars were divided into groups (n = 5). The 5 adhesive systems were applied either in accordance with manufacturers' instructions for solvent drying time (control) or with a prolonged drying time (20-30 seconds). After composite resin was built up on the hybridized surfaces, the teeth were stored for 24 hours and then sectioned to obtain beams that were loaded until fracture. For DC testing, specimens of each adhesive and air-drying condition (n = 3) were evaluated by means of attenuated total reflectance Fourier transform infrared spectroscopy. Data were submitted to 2-way analysis of variance, t test, and Spearman test for correlation analysis. Prolonged air drying resulted in significantly greater DE than did the time suggested by the manufacturers. The adhesives XP Bond and Adper Easy One showed significantly greater uTBS with prolonged air drying. The DC was not affected by air-drying time. No statistically significant correlation was found between DC and uTBS values. Depending on the material, bond strength can be improved by prolonged air-drying times. PMID- 26545279 TI - Effect of a new local anesthetic buffering device on pain reduction during nerve block injections. AB - The purpose of this double-blind, split-mouth, randomized human clinical study was to evaluate the effectiveness of a new sodium bicarbonate local anesthetic buffering device (Onset) in reducing pain associated with dental injections. Twenty patients were given bilateral inferior alveolar (IA) and long buccal (LB) nerve block injections and asked to quantify the pain experienced during injection on a visual analog scale (0, no pain; 10, worst possible pain). One side of the mouth received standard-of-care injections of 2% lidocaine with 1:100,000 epinephrine. On the opposite side, after the buffering device was used to mix the components within the anesthetic carpule, patients received injections of 2% lidocaine with 1:100,000 epinephrine buffered 9:1 with 8.4% sodium bicarbonate. The mean pain scores were 2.7 (SD, 1.3) for buffered and 2.7 (SD, 1.9) for unbuffered IA injections. The mean pain scores were 2.0 (SD, 1.4) for buffered and 2.7 (SD, 1.8) for unbuffered LB injections. The data were analyzed with a paired t test (alpha = 0.05), and no statistically significant difference was found between groups for IA (P = 0.94) or LB (P = 0.17) nerve block injections. In this study of patients receiving common dental nerve block injections, local anesthetic buffering technology did not significantly lessen pain compared to that experienced during a standard unbuffered injection. PMID- 26545280 TI - Space loss following premature loss of primary second molars. AB - This study was designed to evaluate the amount of space loss (SL) caused by premature loss of primary second molars, determine whether the eruption status of permanent first molars is an important factor in the amount of SL, and evaluate the effectiveness of space maintainers (SMs) in SL prevention. SL associated with 100 prematurely extracted primary second molars was evaluated in 87 healthy patients. Teeth were divided into groups based on the use of SMs (36 with SM and 64 without SM). Bitewing and periapical radiographs taken before extraction and 6, 12, 24, 36, and 48 months after extraction were used to determine the amount of SL. Not every patient attended every recall appointment, so the sample size varied at different evaluation times. The most significant amount of SL occurred in the first 12 months after extraction. In patients who did not use an SM, at 6 months there was a mean SL of 2.12 mm (SD, 1.65 mm) and at 12 months there was a mean of 4.02 mm (SD, 1.65), with significantly more SL in the first 6 months (P < 0.001). There was no statistically significant difference in the amount of SL found at 12 and 24 months (P > 0.05). When patients without an SM were grouped by the eruption status of the permanent first molar, there was significantly more SL in the groups with unerupted first molars than there was in the groups with erupted first molars at both 6 months (P < 0.001) and 12 months (P < 0.05). At both 6 and 12 months, the amount of SL in patients who had an SM (n = 13 and n = 14, respectively) was not significantly different from the amount of SL in those who did not have an SM (n = 33 and n = 23, respectively). SMs should be placed as soon as possible following tooth extraction to prevent undue SL. Placement of an SM a year or more after extraction has minimal benefit, since most SL takes place within the first year. SL does occur even when SMs are used. PMID- 26545281 TI - Narrow-implant-retained overdenture in an atrophic mandibular ridge: a case report with 6-year follow-up. AB - When atrophic jaws compromise oral rehabilitation with conventional implants, narrow-diameter implants can be used. This case report describes treatment of an edentulous 75-year-old diabetic woman with a severely resorbed mandibular ridge. Her mandibular dentition was restored with an overdenture supported by 3 narrow implants and 1 mini implant. Her maxillary dentition was restored with a conventional complete denture. A 6-year clinical and radiographic follow-up confirmed that the narrow implants had provided effective stability for the overdenture, providing improvements in phonetics and masticatory ability at a low cost. PMID- 26545282 TI - What every dentist needs to know about obesity and oral health. AB - Obesity has an adverse effect on the body as a whole and greatly increases an individual's risk for numerous diseases, including type 2 diabetes, coronary artery disease, stroke, and cancer. In addition, the link between diabetes and periodontitis has been well documented, and possible links between obesity and other oral health problems, such as caries, are being investigated. As more has been learned about the association between periodontal disease and other inflammatory diseases, including obesity, dentists have gained greater responsibility in the prevention and treatment of chronic diseases. Dentists should be aware of the early signs of obesity and its oral manifestations and equipped with the proper knowledge to educate their patients. This article reviews recent findings on obesity and its relationship to other diseases and in particular to oral health. PMID- 26545283 TI - Accuracy of dental torque wrenches. AB - The aim of this in vitro study was to compare the actual torque of 2 manual wrench systems to their stated (target) torque. New spring- (Nobel Biocare USA, LLC) and friction-style (Zimmer Dental, Inc.) manual dental torque wrenches, as well as spring torque wrenches that had undergone sterilization and clinical use, were tested. A calibrated torque gauge was used to compare actual torque to target torque values of 15 and 35 N/cm. Data were statistically analyzed via mixed-effects regression model with Bonferroni correction. At a target torque of 15 N/cm, the mean torque of new spring wrenches (13.97 N/cm; SE, 0.07 N/cm) was significantly different from that of used spring wrenches (14.94 N/cm; SE, 0.06 N/cm; P < 0.0001). However, the mean torques of new spring and new friction wrenches (14.10 N/cm; SE, 0.07 N/cm; P = 0.21) were not significantly different. For torque measurements calibrated at 35 N/cm, the mean torque of new spring wrenches (35.29 N/cm; SE, 0.10 N/cm) was significantly different (P < 0.0001) from the means of new friction wrenches (36.20 N/cm; SE, 0.08 N/cm) and used spring wrenches (36.45 N/cm; SE, 0.08 N/cm). Discrepancies in torque could impact the clinical success of screw-retained dental implants. It is recommended that torque wrenches be checked regularly to ensure that they are performing to target values. PMID- 26545284 TI - Toothpastes containing abrasive and chemical whitening agents: efficacy in reducing extrinsic dental staining. AB - This in vitro study evaluated the efficacy of toothpastes containing abrasive and chemical whitening agents in reducing the extrinsic discoloration of dental enamel. Sixty slabs of dentin from human teeth were sealed so that only the enamel surface was exposed. The enamel surfaces were photographed for initial color assessment. Staining was performed by immersing the dental slabs in 0.2% chlorhexidine solution for 2 minutes and then in black tea for 60 minutes. This process was repeated 15 times. Photographs were taken at the end of the staining process, and the slabs were divided into 5 groups (n = 12), 3 to be brushed with toothpastes containing chemical whitening agents (2 containing phosphate salts and 1 containing phosphate salts plus hydrogen peroxide) and 2 to represent control groups (ordinary/nonwhitening toothpaste and distilled water). The dental slabs were subjected to mechanical toothbrushing with toothpaste slurry or distilled water, according to each group's specifications. After brushing, more photographs were taken for color analysis. The results showed a significant reduction in luminosity after the staining process in addition to an increase in the colors red and yellow (P < 0.001). After brushing, there was a significant increase in luminosity and a reduction in both red and yellow (P < 0.001). However, there was no observed difference between the changes in color values in dental enamel slabs brushed with whitening toothpastes and the changes found in slabs brushed with ordinary toothpaste. The whitening toothpastes did not outperform an ordinary toothpaste in the removal of extrinsic staining. PMID- 26545285 TI - Digital panoramic radiography versus cone beam computed tomography in the delineation of maxillomandibular tumors. AB - This research aimed to compare the efficacy of digital panoramic radiography (DPR) with that of cone beam computed tomography (CBCT) for delineation of odontogenic and nonodontogenic tumors. From November 2009 through March 2011, 23 tumors in the maxillomandibular complex were diagnosed by histopathological examination. All DPRs and CBCTs were obtained and analyzed by a single previously calibrated radiologist, who considered the following radiographic aspects: clarity of the lesion edges, relation with dental elements, involvement of adjacent anatomical structures, cortical bone expansion and disruption, and, if present, type of involved anatomical structures and site of bone expansion and disruption. Of 23 patients, 15 (65.2%) were male and 8 (34.8%) were female. The tumor was classified as odontogenic in 73.9% of patients and nonodontogenic in 26.1% of patients. Analysis revealed that 56.5% of the tumors were located in the mandible, 34.8% in the maxilla, and 8.7% in both arches. For all analyzed variables, CBCTs offered more accurate details than did DPRs. Panoramic radiography should not be the examination of choice to visualize lesions in the maxillomandibular complex. PMID- 26545286 TI - Modelling extracellular limitations for mediated versus direct interspecies electron transfer. AB - Interspecies electron transfer (IET) is important for many anaerobic processes, but is critically dependent on mode of transfer. In particular, direct IET (DIET) has been recently proposed as a metabolically advantageous mode compared with mediated IET (MIET) via hydrogen or formate. We analyse relative feasibility of these IET modes by modelling external limitations using a reaction-diffusion electrochemical approach in a three-dimensional domain. For otherwise identical conditions, external electron transfer rates per cell pair (cp) are considerably higher for formate-MIET (317 * 10(3) e(-) cp(-1) s(-1)) compared with DIET (44.9 * 10(3) e(-) cp(-1) s(-1)) or hydrogen-MIET (5.24 * 10(3) e(-) cp(-1) s(-1)). MIET is limited by the mediator concentration gradient at which reactions are still thermodynamically feasible, whereas DIET is limited through redox cofactor (for example, cytochromes) activation losses. Model outcomes are sensitive to key parameters for external electron transfer including cofactor electron transfer rate constant and redox cofactor area, concentration or count per cell, but formate-MIET is generally more favourable for reasonable parameter ranges. Extending the analysis to multiple cells shows that the size of the network does not strongly influence relative or absolute favourability of IET modes. Similar electron transfer rates for formate-MIET and DIET can be achieved in our case with a slight (0.7 kJ mol(-1)) thermodynamic advantage for DIET. This indicates that close to thermodynamic feasibility, external limitations can be compensated for by improved metabolic efficiency when using direct electron transfer. PMID- 26545287 TI - Luteolin Inhibits Breast Cancer Development and Progression In Vitro and In Vivo by Suppressing Notch Signaling and Regulating MiRNAs. AB - BACKGROUND/AIMS: This study aims to investigate the effect of Luteolin on breast cancer in vitro and in vivo and the interaction between miRNAs and Notch signaling after Luteolin intervention, and illustrates the possible underlying mechanism and regulation loop. METHODS: Cell growth/survival assays and cell cycle analyses were performed to evaluate cell survival in vitro. Scratch tests, cell invasion assays and tube formation assays were carried out to analyze cell viability and identify the impact of Luteolin on angiogenesis. Critical components in the Notch pathway including proteins and mRNAs were detected by Western blotting analyses, ELISA assays and real-time reverse transcription polymerase chain reaction. Matrix metalloproteinases activity was evaluated by gelatin zymography analyses. MiRNAs were analyzed by miRNA expression assays. After MDA-MB-231 cells were separately transfected with Notch-1 siRNA/cDNA and miRNA mimics, the above assays were also carried out to examine potential tumor cell changes. Xenograft models were applied to evaluate the treatment potency of Luteolin in breast cancer. RESULTS: Luteolin significantly inhibited breast cancer cell survival, cell cycle, tube formation and the expression of Notch signaling-related proteins and mRNAs, and regulated miRNAs. After introducing Notch-1 siRNA and miRNA mimics, MDA-MB-231 cells presented with changes in miRNA levels, reduced Notch signaling-related proteins, and decreased tumor survival, invasion and angiogenesis. CONCLUSION: Luteolin inhibits Notch signaling by regulating miRNAs. However, the effect of miRNAs on the Notch pathway could be either Luteolin-dependent or Luteolin-independent. Furthermore, Notch-1 alteration may inversely change miRNAs levels. Our data demonstrates that Luteolin, miRNAs and the Notch pathway are critical in breast cancer development and prognosis. PMID- 26545288 TI - Effects of the Anger Coping Programme based on cognitive behavioural techniques on adolescents' anger, aggression and psychological symptoms. AB - This study aimed to determine the effects of an Anger Coping Programme based on cognitive behavioural techniques on adolescents' anger, aggression and psychological symptoms. In this randomized controlled experimental study, 385 ninth-year high school students in Turkey were administered the State-Trait Anger Expression Inventory, the Aggression Scale and the Brief Symptom Inventory in 2011-2012. Of the 385 students, 62 who met the inclusion criteria were randomly assigned to experimental and control groups by gender and the scores they obtained from the scales. The students in the experimental group met 1 day a week for 1.5 h, and the study lasted 10 weeks. The scales were administered three times: before the programme was started, immediately after the programme was completed and 6 weeks later. The Anger Coping Programme was effective at reducing students' anger and aggression levels, and a range of psychological symptoms except for somatization. PMID- 26545289 TI - Exonic deletions of AUTS2 in Chinese patients with developmental delay and intellectual disability. AB - Genomic rearrangements involving dosage change of genes have been implicated in a range of developmental disorders. Increasing evidences suggest copy number variations (CNVs) of autism susceptibility candidate gene 2 (AUTS2) are associated with a syndromic form of developmental delay and intellectual disability. However, the genetic and clinical profiles involving AUTS2 variations have not been fully characterized in Asian patients yet, and the outcome of treatments has not been reported. Here we report de novo exonic deletions of AUTS2 detected by chromosomal microarray analysis (CMA) in three Chinese children referred to the clinic for developmental delay, including two deletions involving only exon 6 (98.4 and 262 kb, respectively) and one deletion involving the C terminal of AUTS2 (2147 kb). The phenotypic presentations of these three patients were described and compared with previous cases in literature. In addition, we presented the outcome of hormonal treatment for short stature in one patient. PMID- 26545290 TI - Myths and Facts About the Effects of Ischemic Preconditioning on Performance. PMID- 26545292 TI - Stereolithography of SiOC Ceramic Microcomponents. AB - The first example of the fabrication of complex 3D polymer-derived-ceramic structures is presented with micrometer-scale features by a 3D additive manufacturing (AM) technology, starting with a photosensitive preceramic precursor. Dense and crack-free silicon-oxycarbide-based microparts with features down to 200 MUm are obtained after pyrolysis at 1000 degrees C in a nitrogen atmosphere. PMID- 26545291 TI - Specialised antenatal clinics for women with a multiple pregnancy for improving maternal and infant outcomes. AB - BACKGROUND: Regular antenatal care for women with a multiple pregnancy is accepted practice, and while most women have an increase in the number of antenatal visits, there is no consensus as to what constitutes optimal care. 'Specialised' antenatal clinics have been advocated as a way of improving outcomes for women and their infants. OBJECTIVES: To assess, using the best available evidence, the benefits and harms of 'specialised' antenatal clinics compared with 'standard' antenatal care for women with a multiple pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All published, unpublished, and ongoing randomised controlled trials with reported data that compared outcomes in mothers and babies with a multiple pregnancy who received antenatal care specifically designed for women with a multiple pregnancy (as defined by the trial authors) with outcomes in controls who received 'standard' antenatal care (as defined by the trial authors). DATA COLLECTION AND ANALYSIS: Two of the review authors independently assessed trials for inclusion and trial quality. Both review authors extracted data. Data were checked for accuracy. We graded the quality of the evidence using GRADEpro software. MAIN RESULTS: Findings were based on the results of a single study with some design limitations.Data were available from one study involving 162 women with a multiple pregnancy. For the only reported primary outcome, perinatal mortality, we are uncertain whether specialised antenatal clinics makes any difference compared to standard care (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.26 to 4.03; 324 infants, very low quality evidence). Women receiving specialised antenatal care were significantly more likely to birth by caesarean section (RR 1.38; 95% CI 1.06 to 1.81; 162 women, moderate quality evidence). Data were not reported in the study on the following primary outcomes: small-for-gestational age, very preterm birth or maternal death. There were no differences identified between specialised antenatal care and standard care for other secondary outcomes examined: postnatal depression (RR 0.48; 95% CI 0.19 to 1.20; 133 women, very low quality evidence), breastfeeding (RR 0.63; 95% CI 0.24 to 1.68; 123 women, very low quality evidence), stillbirth (RR 0.68; 0.12 to 4.04) or neonatal death (RR 2.05; 95% CI 0.19 to 22.39) (324 infants). AUTHORS' CONCLUSIONS: There is currently limited information available from randomised controlled trials to assess the role of 'specialised' antenatal clinics for women with a multiple pregnancy compared with 'standard' antenatal care in improving maternal and infant health outcomes. The value of 'specialised' multiple pregnancy clinics in improving health outcomes for women and their infants requires evaluation in appropriately powered and designed randomised controlled trials. PMID- 26545293 TI - Survey of rheumatologists on the use of the Philippine Guidelines on the Screening for Tuberculosis prior to use of Biologic Agents. AB - BACKGROUND: The use of biologic agents has become an important option in treating patients with rheumatoid arthritis. However, these drugs have been associated with an increased risk of tuberculosis (TB) reactivation. Local guidelines for TB screening prior to the use of biologic agents were developed to address this issue. AIM: This study is a survey describing the compliance of Filipino rheumatologists to these guidelines. METHOD: Eighty-seven rheumatologists in the Philippines were given the questionnaire and responses from 61 rheumatologists were included in the analysis. RESULTS: All respondents agree that patients should be screened prior to giving the biologic agents. Local guidelines recommend screening with tuberculin skin test (TST) and chest radiograph. However, cut-off values considered for a positive TST and timing of initiation of biologic agents after starting TB prophylaxis and treatment varied among respondents. In addition, screening of close household contacts were only performed by 41 (69.5%) respondents. There were 11 respondents who reported 16 patients developing TB during or after receiving biologic agents, despite adherence to the guidelines. CONCLUSION: This survey describes the compliance rate of Filipino rheumatologists in applying current local recommendations for TB screening prior to initiating biologic agents. The incidence of new TB cases despite the current guidelines emphasizes the importance of compliance and the need to revise the guidelines based on updated existing literature. PMID- 26545294 TI - Nitrous oxide-based techniques versus nitrous oxide-free techniques for general anaesthesia. AB - BACKGROUND: Nitrous oxide has been used for over 160 years for the induction and maintenance of general anaesthesia. It has been used as a sole agent but is most often employed as part of a technique using other anaesthetic gases, intravenous agents, or both. Its low tissue solubility (and therefore rapid kinetics), low cost, and low rate of cardiorespiratory complications have made nitrous oxide by far the most commonly used general anaesthetic. The accumulating evidence regarding adverse effects of nitrous oxide administration has led many anaesthetists to question its continued routine use in a variety of operating room settings. Adverse events may result from both the biological actions of nitrous oxide and the fact that to deliver an effective dose, nitrous oxide, which is a relatively weak anaesthetic agent, needs to be given in high concentrations that restrict oxygen delivery (for example, a common mixture is 30% oxygen with 70% nitrous oxide). As well as the risk of low blood oxygen levels, concerns have also been raised regarding the risk of compromising the immune system, impaired cognition, postoperative cardiovascular complications, bowel obstruction from distention, and possible respiratory compromise. OBJECTIVES: To determine if nitrous oxide-based anaesthesia results in similar outcomes to nitrous oxide-free anaesthesia in adults undergoing surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014 Issue 10); MEDLINE (1966 to 17 October 2014); EMBASE (1974 to 17 October 2014); and ISI Web of Science (1974 to 17 October 2014). We also searched the reference lists of relevant articles, conference proceedings, and ongoing trials up to 17 October 2014 on specific websites (http://clinicaltrials.gov/, http://controlled-trials.com/, and http://www.centerwatch.com). SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing general anaesthesia where nitrous oxide was part of the anaesthetic technique used for the induction or maintenance of general anaesthesia (or both) with any general anaesthesia using a volatile anaesthetic or propofol-based maintenance of anaesthesia but no nitrous oxide for adults undergoing surgery. Our primary outcome was inhospital case fatality rate. Secondary outcomes were complications and length of stay. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the outcome data. We used meta analysis for data synthesis. Heterogeneity was examined with the Chi2 test and by calculating the I2 statistic. We used a fixed-effect model if the measure of inconsistency was low for all comparisons (I2 statistic < 50%); otherwise we used a random-effects model for measures with high inconsistency. We undertook subgroup analyses to explore inconsistency and sensitivity analyses to evaluate whether the results were robust. We assessed the quality of evidence of the main outcomes using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: We included 35 trials (13,872 adult participants). Seven included studies were at low risk of bias. We identified eight studies as awaiting classification since we could not obtain the full texts, and had insufficient information to include or exclude them. We included data from 24 trials for quantitative synthesis. The results of meta-analyses showed that nitrous oxide-based techniques increased the incidence of pulmonary atelectasis (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18 to 2.10, P = 0.002), but had no effects on the inhospital case fatality rate, the incidence of pneumonia, myocardial infarction, stroke, severe nausea and vomiting, venous thromboembolism, wound infection, or the length of hospital stay. The sensitivity analyses suggested that the results of the meta-analyses were all robust except for the outcomes of pneumonia, and severe nausea and vomiting. Two trials reported length of intensive care unit (ICU) stay but the data were skewed so were not pooled. Both trials reported that nitrous oxide-based techniques had no effects on the length of ICU stay. We rated the quality of evidence for two outcomes (pulmonary atelectasis, myocardial infarction) as high, four outcomes (inhospital case fatality rate, stroke, venous thromboembolism, length of hospital stay) as moderate, and three (pneumonia, severe nausea and vomiting, wound infection rate) as low. AUTHORS' CONCLUSIONS: Given the evidence from this Cochrane review, the avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting. Since there are eight studies awaiting classification, selection bias may exist in our systematic review. PMID- 26545296 TI - Pioneering ambient mass spectrometry imaging in psychiatry: Potential for new insights into schizophrenia. PMID- 26545295 TI - A Kinetic Platform to Determine the Fate of Hydrogen Peroxide in Escherichia coli. AB - Hydrogen peroxide (H2O2) is used by phagocytic cells of the innate immune response to kill engulfed bacteria. H2O2 diffuses freely into bacteria, where it can wreak havoc on sensitive biomolecules if it is not rapidly detoxified. Accordingly, bacteria have evolved numerous systems to defend themselves against H2O2, and the importance of these systems to pathogenesis has been substantiated by the many bacteria that require them to establish or sustain infections. The kinetic competition for H2O2 within bacteria is complex, which suggests that quantitative models will improve interpretation and prediction of network behavior. To date, such models have been of limited scope, and this inspired us to construct a quantitative, systems-level model of H2O2 detoxification in Escherichia coli that includes detoxification enzymes, H2O2-dependent transcriptional regulation, enzyme degradation, the Fenton reaction and damage caused by *OH, oxidation of biomolecules by H2O2, and repair processes. After using an iterative computational and experimental procedure to train the model, we leveraged it to predict how H2O2 detoxification would change in response to an environmental perturbation that pathogens encounter within host phagosomes, carbon source deprivation, which leads to translational inhibition and limited availability of NADH. We found that the model accurately predicted that NADH depletion would delay clearance at low H2O2 concentrations and that detoxification at higher concentrations would resemble that of carbon-replete conditions. These results suggest that protein synthesis during bolus H2O2 stress does not affect clearance dynamics and that access to catabolites only matters at low H2O2 concentrations. We anticipate that this model will serve as a computational tool for the quantitative exploration and dissection of oxidative stress in bacteria, and that the model and methods used to develop it will provide important templates for the generation of comparable models for other bacterial species. PMID- 26545297 TI - Changes in cholinergic and glutamatergic markers in the striatum from a sub-set of subjects with schizophrenia. AB - BACKGROUND/OBJECTIVES: Having separated a sub-group of people with schizophrenia based on a marked loss of cortical [(3)H]pirenzepine binding (MRDS); we wished to determine if MRDS had lower levels of [(3)H]pirenzepine and other muscarinic receptor antagonist binding to the striatum and if this was due to loss of pre- or post-synaptic neurons or glia measured using surrogate markers (25 kilodalton synaptosomal-associated protein (SNAP 25), postsynaptic density protein 95 (PSD 95), glial fibrillary acidic protein (GFAP) 41/43) of cell number. METHODS: [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]4-DAMP binding to the striatum from 37 subjects with schizophrenia (19 MRDS) and 20 controls as well as SNAP 25, PSD 95 and GFAP 41/43 in crude particulate membrane were measured. RESULTS: [(3)H]pirenzepine and [(3)H]AF-DX 384 binding to the striatum were significantly lower in schizophrenia due to lower binding of both radioligands in the striatum from MRDS. Levels of PSD 95 were higher in schizophrenia, predominantly due to higher levels in MRDS. CONCLUSIONS: Our data suggest muscarinic M1 ([(3)H]pirenzepine) and M2 and/or M4 receptors ([(3)H]AF-DX 384) are lower in the striatum from MRDS which could mediate inappropriate adaption to internal and external cues which, in turn, would affect motivation, cognition and motor control. Increased levels of PSD 95 could indicate increased post-synaptic boutons or changes in NMDA receptor-mediated signalling in MRDS. PMID- 26545299 TI - The Community Assessment of Psychic Experiences measures nine clusters of psychosis-like experiences: A validation of the German version of the CAPE. AB - AIM: This study examined the factorial and criterion validity of the Community Assessment of Psychic Experiences (CAPE). We compared the validity of the original three-dimensional model and a recently proposed multidimensional model, in which positive symptoms are subdivided into the subfactors hallucinations, bizarre experiences, paranoia, grandiosity and magical thinking and negative symptoms are subdivided into social withdrawal, affective flattening and avolition. METHODS: Eleven community (n=934) and three patient samples (n=112) were combined and the proposed models were tested using confirmatory factor analysis. Criterion validity was calculated based on self-report measures for depression and paranoia as well as observer-based ratings for positive and negative symptoms. RESULTS: The multidimensional model showed better relative quality (AIC, BIC) than the original three-dimensional model of the CAPE, but both models showed acceptable absolute model-fit (RMSEA, SRMR). The criterion validity was good for the positive symptom scales and negative symptom subfactors social withdrawal and affective flattening. CONCLUSION: Factorial validity was found for the three-dimensional and multidimensional model for the CAPE. The multidimensional model, however, shows better comparative fit and promising results in regard to criterion validity. Thus, we recommend a hierarchical multidimensional structure of positive and negative symptoms for future use of the CAPE. PMID- 26545298 TI - Gender differences in the treatment of first-episode schizophrenia: Results from the European First Episode Schizophrenia Trial. AB - Gender differences in the response to antipsychotic treatment have been detected in the past, but not studied in great detail. The results of the European First Episode Schizophrenia Trial (EUFEST) were analyzed with a focus on gender differences in the response to randomized treatment of first-episode schizophrenia. A total of 498 patients (298 men and 200 women) were randomly assigned by a web-based online system to open-label treatment with haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone. Treatment response was evaluated using the positive and negative syndrome scale (PANSS). Data were collected at baseline and then prospectively for one year. Baseline characteristics (age and proportion of patients assigned to individual antipsychotics) were the same between the male and female patients with the exception of ziprasidone: significantly fewer men, proportionately, were prescribed ziprasidone. There was no significant difference between genders between the initial total PANSS and subscale scores. A significant interaction between time and gender was found, with more robust PPANSS and TPANSS score improvement in women during the course of treatment. Of all of the antipsychotics used, only olanzapine led to significantly greater improvement in the total PANSS score in women during the follow-up period. Gender differences should be given more attention in research and clinical practice. Their causes require clarification, and future strategies for dealing with them may be considered in early intervention programs and guidelines. PMID- 26545300 TI - Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance. AB - Dihydroxylated E,E,Z-docosatrienes are acyclic lipoxygenase metabolites of 22 carbon atom polyunsaturated fatty acids (PUFAs) containing a conjugated E,E,Z triene flanked by two secondary allylic alcohols. The two main metabolites, protectin D1 (PD1) and its regioisomer maresin 1 (MaR1), were shown to be actively involved in the resolution and more specifically the termination of the inflammation process. Studies directed at the synthesis of E,E,Z-docosatrienes have been undertaken to resolve stereochemical ambiguities, and provide standards for biological evaluation and reference samples for in-vivo detection and lipidomic analyses. In this review we provide a brief update of the literature on the biological significance of E,E,Z-docosatrienes and the role that synthetic organic chemists has played in the development of these lipids, providing an overview and comparison of the different strategies employed to access synthetic E,E,Z-docosatriene standards. PMID- 26545301 TI - Feeding response following central administration of mesotocin and arginine vasotocin receptor agonists in chicks (Gallus gallus). AB - Mesotocin (MT) and arginine-vasotocin (AVT) are posterior pituitary derived hormones in birds and are homologous to mammalian oxytocin (OT) and vasopressin (VP), respectively. We previously reported that intracerebroventricular (ICV) injection of both MT and AVT inhibit feeding and induce wing-flapping in chicks (Gallus gallus). Because both peptides cause similar effects suggests that they might act via common receptors. However, the specific receptors of MT and AVT which mediate their anorexigenic effect have not been clarified in chicks. Thus, the purpose of the present study was to identify the receptor subtypes involved in MT- and AVT-induced anorexia and behavioral patterns by using several agonists. ICV injection of vasopressin-1 receptor agonist (V1R) (homologous to chicken AVT receptor-2 and -4 [VT2R and VT4R, respectively]), significantly decreased food intake while agonists of vasopressin-2 receptor (V2R) and OT receptor (OTR) (homologues of chicken AVT receptor-1 and MT receptor respectively) had no effect. In addition, V1R agonist induced wing-flapping although this was not affected by V2R or OTR agonists. Since VT2R has not been found in the brain of chicks, the present study suggested that VT4R might be related to the anorexigenic effect and wing-flapping induced by MT and AVT in chicks. PMID- 26545302 TI - In Response to Management of a Pediatric Snake Envenomation After Presentation With a Tight Tourniquet by Bush and Kinlaw. PMID- 26545303 TI - Instability of hydrogenated TiO2. AB - Hydrogenated TiO2 (H-TiO2) is touted as a viable visible light photocatalyst. We report a systematic study on the thermal stability of H-implanted TiO2 using nuclear reaction analysis (NRA), Rutherford backscattering spectrometry, ultraviolet photoelectron spectroscopy, and X-ray photoelectron spectroscopy. Protons (40 keV) implanted at a ~2 atom % level within a ~120 nm wide profile of rutile TiO2(110) were situated ~300 nm below the surface. NRA revealed that this H-profile broadened toward the surface after annealing at 373 K, dissipated out of the crystal into vacuum at 473 K, and was absent within the beam sampling depth (~800 nm) at 523 K. Photoemission showed that the surface was reduced in concert with these changes. Similar anneals had no effect on pristine TiO2(110). The facile bulk diffusivity of H in rutile at low temperatures, as well as its interfacial activity toward reduction, significantly limits the utilization of H TiO2 as a photocatalyst. PMID- 26545304 TI - Mobile applications for diabetes management: efficacy issues and regulatory challenges. PMID- 26545305 TI - Medial Soft-Tissue Realignment Versus Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation: Systematic Review. AB - PURPOSE: To compare the clinical outcomes between medial soft-tissue surgery and medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation without any evident predisposing factors. METHODS: A literature search was performed on the established medical databases MEDLINE, EMBASE, and the Cochrane register. The inclusion criteria were as follows: English-language papers for recurrent patellar dislocation without any evident predisposing factors, clinical trial(s) with clear description of surgical technique, adult subjects, medial soft-tissue surgery or MPFL reconstruction without combined surgery, and a follow-up longer than 2 years. The methodological quality of all articles was assessed by 2 authors according to the Coleman methodology score. RESULTS: Thirteen studies (mean Coleman methodology score value, 74.1; standard deviation, 11.5) were included in the analysis. Five studies reported the outcomes of patients undergoing medial soft-tissue surgery, compared with 7 studies reporting MPFL reconstruction. Overall, 109 patients underwent medial soft-tissue surgery with a minimum 2-years follow-up, compared with 308 patients of MPFL reconstruction. There was one direct comparative study between medial soft-tissue surgery and MPFL reconstruction. Of the patients who received medial soft-tissue surgery, 0 to 9.7% experienced redislocation, compared with 0 to 10.7% of the MPFL reconstruction group. The ranges of differences in Kujala scores were 23.6 to 31.7 points in patients who underwent medial soft-tissue surgery and 23.11 to 38.8 points in patients who underwent MPFL reconstruction. The ranges of postoperative congruence angles were -14.4 degrees to 8.2 degrees for medial soft-tissue surgery and -7.7 degrees to -5.2 degrees for MPFL reconstruction. The ranges of postoperative lateral patellofemoral angles were 7.9 degrees to 9.4 degrees for medial soft-tissue surgery and 5 degrees to 5.3 degrees for MPFL reconstruction. CONCLUSIONS: All studies on medial soft-tissue surgery and MPFL reconstruction for recurrent patellar dislocation without predisposing factors showed satisfactory outcomes despite the use of numerous surgical techniques, graft types, and follow-up periods. LEVEL OF EVIDENCE: Level IV, Systematic Review. PMID- 26545306 TI - Long-Term Examination of Bone Mineral Density in the Calcanei After Anterior Cruciate Ligament Reconstruction in Adolescents and Matched Adult Controls. AB - PURPOSE: The aims were to evaluate the results 10 to 20 years after anterior cruciate ligament (ACL) reconstruction performed in adolescents in terms of bone mineral density (BMD) in the calcanei using the dual-energy x-ray absorptiometry (DXA) technique, activity level, and quality of life. METHODS: A case-control study of adolescents who underwent ACL reconstruction between 1992 and 2002 was performed. The inclusion criterion was a unilateral ACL injury. The exclusion criteria were bilateral ACL injury, contralateral ACL reconstruction, posterior cruciate ligament injury, and previous or present fractures of either lower extremity. The BMD was measured in both calcanei using the DXA technique and compared with a control group of adult ACL-reconstructed patients and with a DXA reference database. The age of the control group was similar to that of the patient group at the time of BMD assessment, performed 60 months after reconstruction. Activity was measured with the Tegner activity scale. The EQ-5D was used to evaluate quality of life. RESULTS: Thirty-two adolescents (11 boys and 21 girls), aged 12 to 16 years, with a symptomatic unilateral ACL rupture, underwent reconstruction at near skeletally mature age. Of these patients, 29 (91%) took part in the follow-up examination. The BMD values for the male patients were lower on the injured and non-injured sides (-15.2% [P = .02] and 11.8% [P = .05], respectively) compared with the control group. The values for the female patients were -0.8% (P = .84) and -2.2% (P = .69), respectively. Correspondingly, the BMD values for the male patients were lower on the injured and non-injured sides (-8.2% and -4.9%, respectively) compared with the male reference database. The BMD values for the female patients were higher on the injured and non-injured sides (4.1% and 4.3%, respectively) compared with the female reference database. In the control group, female patients had a significantly lower value for the Tegner activity scale preoperatively (median, 2.0; range, 0 to 5) than the female patients in the study group (median, 3.0; range, 2 to 8) (P = .006). In the study group, the Tegner activity scale at follow-up showed a significant correlation with the BMD on the injured side for male patients (rho = 0.67, P = .03) but not on the non-injured side (rho = 0.50, P = .14). In the control group, the Tegner activity scale at follow-up showed a significant correlation with the BMD on the non-injured side for female patients (rho = 0.61, P = .03) but not on the injured side (rho = 0.34, P = .25). The Tegner activity scale and EQ-5D showed no significant differences between the study groups. CONCLUSIONS: In the long-term, the BMD in the calcanei of patients who were adolescents at the time of ACL reconstruction differed from that of a control group and a reference database. This study indicates that boys with an ACL injury and subsequent ACL reconstruction run a subsequent risk of a significantly lower BMD in their calcanei as adults and, consequently, an increased future fracture risk. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 26545307 TI - Comparative Biomechanical Study on Contact Alterations After Lateral Meniscus Posterior Root Avulsion, Transosseous Reinsertion, and Total Meniscectomy. AB - PURPOSE: To compare the effects of lateral meniscus posterior root avulsion left in situ, its repair, and meniscectomy on contact pressure distribution in both tibiofemoral compartments at different flexion angles. METHODS: Eight cadaveric knees were tested under compressive 1000 N load for 4 lateral meniscus conditions (intact, posterior root avulsion, transosseous root repair, and total meniscectomy) at flexion angles 0 degrees , 30 degrees , 60 degrees , and 90 degrees . Contact area and pressure distribution were registered using K-scan pressure sensors inserted between menisci and tibial plateau. RESULTS: In the lateral compartment, root detachment decreased contact area (P = .017, 0 degrees and 30 degrees ; P = .012, 60 degrees and 90 degrees ) and increased mean (P = .012, all angles) and maximum (P = .025, 0 degrees and 30 degrees ; P = .017, 60 degrees ; P = .012, 90 degrees ) pressures relative to intact condition. Repair restored all measured parameters close to intact at 0 degrees , but effectiveness decreased with flexion angle, yielding no significant effect at 90 degrees . Meniscectomy produced higher decreases than root avulsion in contact area (P = .012, 0 degrees and 90 degrees ; P = .05, 30 degrees and 60 degrees ) and increases in mean (P = .017, 0 degrees and 30 degrees ; P = .018, 90 degrees ) and maximum pressure (P = .012, 0 degrees ; P = .036, 30 degrees ). In the medial compartment, lesion changed the contact area at high flexion angles only, while meniscectomy induced greater changes at all angles. CONCLUSIONS: Lateral meniscus posterior root avulsion generates significant alterations in contact area and pressures at lateral knee compartment for flexion angles between full extension and 90 degrees . Meniscectomy causes greater disorders than the avulsion left in situ. Transosseous repair with a single suture restores these alterations to conditions close to intact at 0 degrees and 30 degrees but not at 60 degrees and 90 degrees . CLINICAL RELEVANCE: Altered contact mechanics after lateral meniscus posterior root avulsion might have degenerative consequences. Transosseous repair with one suture should be revised to effectively restore contact mechanics at high flexion angles. PMID- 26545308 TI - Comorbidity and pathogenic links of chronic spontaneous urticaria and systemic lupus erythematosus--a systematic review. AB - Chronic spontaneous urticaria (CSU) is a common mast cell-driven disease characterized by the development of wheals (hives), angioedema (AE), or both for > 6 weeks. It is thought that autoimmunity is a common cause of CSU, which is often associated with autoimmune thyroiditis, whereas the link to other autoimmune disorders such as systemic lupus erythematosus (SLE) has not been carefully explored. Here, we systematically reviewed the existing literature for information on the prevalence of CSU in SLE (and vice versa) and we examined the possible clinical and pathogenetic relationship between CSU and SLE. The prevalence of CSU and CSU-like rash in SLE was investigated by 42 independent studies and comorbidity in adult patients reportedly ranged from 0% to 21.9% and 0.4% to 27.5%, respectively (urticarial vasculitis: 0-20%). In children with SLE, CSU was reported in 0-1.2% and CSU-like rash in 4.5-12% (urticarial vasculitis: 0 2.2%). In contrast, little information is available on the prevalence of SLE in patients with CSU, and more studies are needed to determine the rate of comorbidity. Recent insights on IgG- and IgE-mediated autoreactivity suggest similarities in the pathogenesis of CSU and SLE linking inflammation and autoimmunity with the activation of the complement and coagulation system. Future studies of patients with either or both conditions could help to better define common pathomechanisms in CSU and SLE and to develop novel targeted treatment options for patients with CSU and SLE. PMID- 26545309 TI - Optical diagnostics study of air flow and powder fluidisation in Nexthaler(r)- Part I: Studies with lactose placebo formulation. AB - Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler(r) is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into "transparent" Nexthaler(r) to allow application of high-speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (~20ms) after withdrawal of the dose protector followed by powder emission from the device within ~50ms thereafter. The bulk of the metered placebo dose was emitted within 100-200ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler(r) DPI will be very beneficial for carrier-drug de-aggregation. PMID- 26545310 TI - Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent. AB - Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37+/-0.5 degrees C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin(r) tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin(r) tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin(r). This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. PMID- 26545311 TI - Revision surgery for recurrent and persistent carpal tunnel syndrome: Clinical results and factors affecting outcomes. AB - Thirty-eight hands in 36 patients with recurrent or persistent carpal tunnel syndrome (CTS) were reviewed retrospectively after a mean of 51 months (range 12 86) to identify factors that may lead to poor outcomes after surgical management. Clinical assessment focused on pain and sensitivity recovery, measured with a VAS and Weber's two-point discrimination test, respectively. At the latest follow-up, we found 11 excellent, 15 good, nine fair and three poor results. The risk of fair or poor results was significantly higher in the presence of intraneural fibrosis, severe preoperative sensory deficit, neuroma of the palmar cutaneous branch of the median nerve, workers compensation claims and number of previous surgeries. This last factor also significantly increased the risk of intraneural fibrosis. Despite disappointing outcomes, identification of these factors may improve our prognostic ability for revision surgery in cases of recurrent CTS. PMID- 26545312 TI - A rare cause of ulnar nerve entrapment at the elbow area illustrated by six cases: The anconeus epitrochlearis muscle. AB - Ulnar nerve entrapment is the second most common compressive neuropathy after carpal tunnel syndrome. The accessory anconeus epitrochlearis muscle - present in 4% to 34% of the general population - is a known, but rare cause of ulnar nerve entrapment at the elbow. The aim of this article was to expand our knowledge about this condition based on six cases that we encountered at our hospital between 2011 and 2015. Every patient had a typical clinical presentation: hypoesthesia or sensory deficit in the fourth and fifth fingers; potential intrinsics atrophy of the fourth intermetacarpal space; loss of strength and difficulty with fifth finger abduction. Although it can be useful to have the patient undergo ultrasonography or MRI to aid in the diagnosis, only electromyography (EMG) was performed in our patients. EMG revealed clear compression in the ulnar groove, with conduction block and a large drop in nerve conduction velocity. Treatment typically consists of conservative treatment first (splint, analgesics). Surgical treatment should be considered when conservative treatment has failed or the patient presents severe neurological deficits. In all of our patients, the ulnar nerve was surgically released but not transposed. Five of the six patients had completely recovered after 0.5 to 4years follow-up. Ulnar nerve entrapment at the elbow by the anconeus epitrochlearis muscle is not common, but it must not be ignored. Only ultrasonography, MRI or, preferably, surgical exploration can establish the diagnosis. EMG findings such as reduced motor nerve conduction velocity in a short segment of the ulnar nerve provides evidence of anconeus epitrochlearis-induced neuropathy. PMID- 26545313 TI - Further thoughts on "metaphor blindness": Implications and future avenues of research. PMID- 26545314 TI - Diagnostic inexactitude - Reframing and relabelling Disruptive Mood Dysregulation Disorder for ICD-11 does not solve the problem. PMID- 26545315 TI - Emergency admissions for major haemorrhage associated with direct oral anticoagulants. AB - INTRODUCTION: To describe the population admitted in an emergency department of a teaching hospital for severe bleeding associated with direct oral anticoagulants (DOAC). METHOD: During a three-year period (2012-2014) patients older than 16 years were prospectively identified by haemorrhagic symptoms from computerised requests. At least one of the following criteria defined major haemorrhage: haemorrhagic shock, unstable haemodynamic, need for transfusion or haemostatic procedure, or a life threatening location. RESULTS: Fifty four patients, 23 receiving dabigatran, 30 rivaroxaban and one apixaban were included, 2 in 2012, 35 in 2013 and 17 in 2014. Median age was 84 years (range 63-99) with a sex ratio of 1.16. Haemorrhagic complications were gastrointestinal (n=27), intracranial (n=12) or miscellaneous (n=15). Indication of DOAC was stroke prevention in atrial fibrillation in 49 cases and deep vein thrombosis in 5 cases. Hospitalization was required for 45 patients (83%) with a mean length of stay of 8.5 days. Sixteen patients needed intensive care. Reversal therapy was prescribed in 11 patients. At 1 month, overall mortality was 24%, reaching 41.7% for intracranial haemorrhage. Among surviving patients, DOAC was stopped in 10 cases, continued in 17 patients and switched for other antithrombotic in 17 patients. CONCLUSION: Our study contributes to the post marketing surveillance of major haemorrhagic complications associated with DOAC. It takes part to the knowledge about the course of this severe event in emergencies. Careful awareness in risk benefit assessment, especially in elderly, is needed. PMID- 26545316 TI - Visual Outcomes after Proton Beam Irradiation for Choroidal Melanomas Involving the Fovea. AB - PURPOSE: To report visual outcomes in patients undergoing proton beam irradiation of tumors located within 1 disc diameter of the fovea. DESIGN: Retrospective review. PARTICIPANTS: Patients with choroidal melanoma involving the fovea treated with proton beam therapy between 1975 and 2009. METHODS: Three hundred fifty-one patients with choroidal melanomas located 1 disc diameter (DD) or less from the fovea and more than 1 DD away from the optic nerve were included in this study. In a subgroup of 203 of the patients with small and medium choroidal melanomas, the effect of a reduced dose of radiation, 50 Gy (relative biological effectiveness [RBE]) versus 70 Gy (RBE), on visual outcomes was analyzed. The Kaplan-Meier method and Cox regression analysis were performed to calculate cumulative rates of vision loss and to assess risk factors for vision loss, respectively. MAIN OUTCOME MEASURES: Visual acuity and radiation complications, which included radiation maculopathy, papillopathy, retinal detachment, and rubeosis, were assessed. RESULTS: Three hundred fifty-one patients were included in this study with a mean follow-up time of 68.7 months. More than one-third of patients (35.5%) retained 20/200 or better vision 5 years after proton beam irradiation. For those patients with a baseline visual acuity of 20/40 or better, 16.2% of patients retained this level of vision 5 years after proton beam irradiation. Tumor height less than 5 mm and baseline visual acuity 20/40 or better were associated significantly with a better visual outcome (P < 0.001). More than two-thirds (70.4%) of patients receiving 50 Gy (RBE) and nearly half (45.1%) of patients receiving 70 Gy (RBE) retained 20/200 or better vision 5 years after treatment, but this difference was not significant. Approximately 20% of patients with these smaller macular tumors retained 20/40 vision or better 5 years after irradiation. CONCLUSIONS: The results of this retrospective analysis demonstrate that despite receiving a full dose of radiation to the fovea, many patients with choroidal melanoma with foveal involvement maintain useful vision. A radiation dose reduction from 70 to 50 Gy (RBE) did not seem to increase the proportion of patients who retain usable vision. PMID- 26545317 TI - Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study). AB - PURPOSE: The Geographic Atrophy Progression (GAP) study was designed to assess the rate of geographic atrophy (GA) progression and to identify prognostic factors by measuring the enlargement of the atrophic lesions using fundus autofluorescence (FAF) and color fundus photography (CFP). DESIGN: Prospective, multicenter, noninterventional natural history study. PARTICIPANTS: A total of 603 participants were enrolled in the study; 413 of those had gradable lesion data from FAF or CFP, and 321 had gradable lesion data from both FAF and CFP. METHODS: Atrophic lesion areas were measured by FAF and CFP to assess lesion progression over time. Lesion size assessments and best-corrected visual acuity (BCVA) were conducted at screening/baseline (day 0) and at 3 follow-up visits: month 6, month 12, and month 18 (or early exit). MAIN OUTCOME MEASURES: The GA lesion progression rate in disease subgroups and mean change from baseline visual acuity. RESULTS: Mean (standard error) lesion size changes from baseline, determined by FAF and CFP, respectively, were 0.88 (0.1) and 0.78 (0.1) mm(2) at 6 months, 1.85 (0.1) and 1.57 (0.1) mm(2) at 12 months, and 3.14 (0.4) and 3.17 (0.5) mm(2) at 18 months. The mean change in lesion size from baseline to month 12 was significantly greater in participants who had eyes with multifocal atrophic spots compared with those with unifocal spots (P < 0.001) and those with extrafoveal lesions compared with those with foveal lesions (P = 0.001). The mean (standard deviation) decrease in visual acuity was 6.2 +/- 15.6 letters for patients with image data available. Atrophic lesions with a diffuse (mean 0.95 mm(2)) or banded (mean 1.01 mm(2)) FAF pattern grew more rapidly by month 6 compared with those with the "none" (mean, 0.13 mm(2)) and focal (mean, 0.36 mm(2)) FAF patterns. CONCLUSIONS: Although differences were observed in mean lesion size measurements using FAF imaging compared with CFP, the measurements were highly correlated with one another. Significant differences were found in lesion progression rates in participants stratified by hyperfluorescence pattern subtype. This large GA natural history study provides a strong foundation for future clinical trials. PMID- 26545318 TI - Boston Type 1 Keratoprosthesis versus Repeat Donor Keratoplasty for Corneal Graft Failure: A Systematic Review and Meta-analysis. AB - PURPOSE: To compare repeat penetrating keratoplasty (PK) with Boston type I keratoprosthesis (KPro) implantation for full-thickness donor corneal graft failure. DESIGN: Previous donor graft failure is a common indication for both PK and KPro implantation. Selection of the surgical procedure is entirely dependent on the surgeon because there are no studies available for guidance. Therefore, a systematic review was undertaken to examine vision, device retention, graft clarity, and postoperative glaucoma and infection outcomes after repeat PK versus KPro implantation. METHODS: Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States. Visual acuity at 2 years was the primary outcome measure. The proportion of clear grafts in the repeat PK group, device retention in the KPro group, and the development of postoperative glaucoma and infection were secondary outcome measures. RESULTS: The search strategy identified 17 128 articles in the PK analysis. After screening, 26 studies (21 case series and 5 cohort studies) were included in the review. Pooled analysis of the 26 unique studies demonstrated a 42% (95% confidence interval [CI], 30%-56%) likelihood of maintaining 20/200 or better at 2 years after repeat PK, compared with an 80% (95% CI, 68%-88%) probability with KPro implantation. The probability of maintaining a clear graft at 5 years was 47% (95% CI, 40%-54%) after repeat PK, whereas the probability of retention of the KPro at 5 years was 75% (95% CI, 64%-84%). The rate of progression of glaucoma at 3 years was 25% (95% CI, 10%-44%) after repeat PK and 30% in the KPro cohort. CONCLUSIONS: These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK. PMID- 26545319 TI - Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering: Loss of alpha-Crystallin Leads to Nuclear Cataract Development. AB - PURPOSE: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, alpha crystallin. DESIGN: Natural history and cohort study. PARTICIPANTS: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department. METHODS: All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound alpha-crystallin level in the nucleus, the alpha-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes. MAIN OUTCOME MEASURES: alpha-Crystallin Index (ACI) and AREDS nuclear cataract grade. RESULTS: Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost alpha-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery. CONCLUSIONS: This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound alpha-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device. PMID- 26545321 TI - Factors Associated with Patient Press Ganey Satisfaction Scores for Ophthalmology Patients. AB - PURPOSE: To determine which metrics from the Press Ganey patient satisfaction survey best correlate with "likelihood to recommend" among patients in an academic tertiary medical center practice setting. DESIGN: Cross-sectional study. PARTICIPANTS: Over a 3-month period, patients presenting to an academic practice who agreed to participate were enrolled in the study if they met the following entry criteria: (1) age >=18 years, (2) ability to read and speak English, and (3) followed in this practice between 4 months and 4 years. A total of 196 patients were recruited. METHODS: A 26-item abridged version of the Press Ganey survey typically distributed to patients via mail or e-mail after visiting the Stanford University Hospital was administered privately to each eligible patient of 2 different attending clinics at the conclusion of his or her visit. The 26 survey items were not modified for the purposes of the study and were administered such that participants could not be individually identified. The arithmetic mean score for the item "Likelihood of your recommending our practice to others" was calculated by assigning a value (0-100) to the Likert value associated with survey responses and correlated with the 25 other items using the differences in the mean scores. MAIN OUTCOME MEASURES: Response to survey items graded on a 1 to 5 standard Likert scale. RESULTS: The weighted mean patient survey score for the "likelihood to recommend" item for the junior faculty member was 95.9% and for the senior faculty member was 94.5%, respectively. For the remaining 25 items, "Amount of time the care provider spent with you" (Diff[1 2]=1.03; P < 0.0001) and "Ease of scheduling your appointment" (Diff[1-2]=0.99; P < 0.0001) best correlated with likelihood to recommend. In contrast, "Friendliness/courtesy of the care provider" (Diff[1-2]=0.29; P = 0.0045) correlated least with likelihood to recommend. Stratification based on provider did not affect the study results. CONCLUSIONS: The perception of time spent with the practitioner and ease of appointment scheduling are the 2 variables that best correlate with patients recommending their ophthalmologists to other prospective patients. PMID- 26545320 TI - Association between Antiplatelet or Anticoagulant Drugs and Retinal or Subretinal Hemorrhage in the Comparison of Age-Related Macular Degeneration Treatments Trials. AB - PURPOSE: To evaluate the association between use of antiplatelet or anticoagulant drugs and retinal or subretinal hemorrhage in participants with neovascular age related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT). DESIGN: Cohort study within CATT. PARTICIPANTS: Participants in CATT with untreated active neovascular AMD (n = 1185). METHODS: Participants were interviewed for use of antiplatelet or anticoagulant drugs. Trained readers evaluated photographs for the presence and size of retinal or subretinal hemorrhage at baseline and years 1 and 2. Associations between use of antiplatelet or anticoagulant drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using multivariate logistic regression models. MAIN OUTCOME MEASURES: Odds ratio for association with antiplatelet or anticoagulant use. RESULTS: Among 1165 participants with gradable photographs, 724 (62.1%) had retinal or subretinal hemorrhage at baseline; 84.4% of hemorrhages were 1 disc area (DA) or less, 8.1% were 1 to 2 DA, and 7.5% were more than 2 DA. At baseline, 608 participants (52.2%) used antiplatelet or anticoagulant drugs, including 514 participants (44.1%) using antiplatelets only, 77 (6.6%) using anticoagulants only, and 17 (1.5%) using both. Hemorrhage was present in 64.5% of antiplatelet or anticoagulant users and in 59.6% of nonusers (P = 0.09; adjusted odds ratio [OR], 1.18; 95% confidence interval, 0.91-1.51; P = 0.21). Neither presence nor size of baseline hemorrhage was associated with the type, dose, or duration of antiplatelet or anticoagulant use. Forty-four of 1078 participants (4.08%) had retinal or subretinal hemorrhage detected on 1- or 2 year photographs; these hemorrhages were not associated with antiplatelet or anticoagulant use at baseline (P = 0.28) or during follow-up (P = 0.64). Among participants with hypertension (n = 807), antiplatelet or anticoagulant use was associated with a higher rate of hemorrhage at baseline (66.8% vs. 56.4%; adjusted OR, 1.48; P = 0.01), but not size of retinal or subretinal hemorrhage (P = 0.41). CONCLUSIONS: Most retinal or subretinal hemorrhages in eyes enrolled in CATT were less than 1 DA. Among all CATT participants, antiplatelet or anticoagulant use was not associated significantly with hemorrhage, but it was associated significantly with hemorrhage in participants with hypertension. PMID- 26545322 TI - A PCR-based approach to assess genomic DNA contamination in RNA: Application to rat RNA samples. AB - Genomic DNA (gDNA) contamination of RNA samples can lead to inaccurate measurement of gene expression by reverse transcription quantitative real-time PCR (RT-qPCR). We describe an easily adoptable PCR-based method where gDNA contamination in RNA samples is assessed by comparing the amplification of intronic and exonic sequences from a housekeeping gene. Although this alternative assay was developed for rat RNA samples, it could be easily adapted to other species. As a proof of concept, we assessed the effects of detectable gDNA contamination levels on the expression of a few genes that illustrate the importance of RNA quality in acquiring reliable data. PMID- 26545323 TI - Rapid method for protein quantitation by Bradford assay after elimination of the interference of polysorbate 80. AB - Bradford assay is one of the most common methods for measuring protein concentrations. However, some pharmaceutical excipients, such as detergents, interfere with Bradford assay even at low concentrations. Protein precipitation can be used to overcome sample incompatibility with protein quantitation. But the rate of protein recovery caused by acetone precipitation is only about 70%. In this study, we found that sucrose not only could increase the rate of protein recovery after 1 h acetone precipitation, but also did not interfere with Bradford assay. So we developed a method for rapid protein quantitation in protein drugs even if they contained interfering substances. PMID- 26545324 TI - Fish IRF3 up-regulates the transcriptional level of IRF1, IRF2, IRF3 and IRF7 in CIK cells. AB - Interferon Regulatory Factors (IRFs) belong to a family of transcription factor involved in transcriptional regulation of type I IFN and IFN-stimulated genes (ISG) in cells. In the present study, an IRF3 full-length cDNA (termed CiIRF3, JX999055) and its promoter sequence were cloned by homology cloning strategy and genome walking from grass carp (Ctenopharyngodon idella). The full-length cDNA sequence of CiIRF3 is comprised of a 5'UTR (195 bp), a 3'UTR (269 bp) and a largest open reading frame (ORF) of 1377 bp encoding a polypeptide of 458 amino acids. CiIRF3 has a conservative DNA-binding domain (DBD) at N-terminal and a relatively conserved interferon regulatory factors association domain (IAD). Phylogenetic tree analysis indicated that CiIRF3 gathers together with other IRF 3 from higher vertebrates in the same branch. The promoter sequence of CiIRF3 (596 bp) consists of three IRF-E, a C/EBP beta, a NF-kappa B and a TATA-BOX. CiIRF3 was constitutively expressed at low level in different grass carp tissues but was rapidly up-regulated with Poly I:C stimulation. To study the molecular mechanism of CiIRF3 regulating the transcription of IRFs, CiIRF3 was expressed in Escherichia coli BL21 and purified by affinity chromatography with the Ni-NTA His Bind Resin. Gel mobility shift assays revealed the affinity of CiIRF3 protein with promoters of CiIRF1, CiIRF2, CiIRF3 and CiIRF7 respectively. Then, CIK cells were co-transfected with pcDNA3.1-CiIRF3, pGL3-promotor (pGL3-CiIRF1, pGL3 CiIRF2, pGL3-CiIRF3, pGL3-CiIRF7) and luciferase reporter vector respectively. The cotransfection experiment showed that CiIRF3 increased the promoter activity of CiIRF1, CiIRF2, CiIRF3 and CiIRF7. Furthermore, overexpression of CiIRF3 in CIK cells also up-regulated the expressions of CiIRF1, CiIRF2, CiIRF3 and CiIRF7. So, CiIRF3 can improve the transcriptional level of CiIRF1, CiIRF2, CiIRF3 and CiIRF7. PMID- 26545325 TI - Reconstructing exposures from biomarkers using exposure-pharmacokinetic modeling- A case study with carbaryl. AB - Sources of uncertainty involved in exposure reconstruction for short half-life chemicals were characterized using computational models that link external exposures to biomarkers. Using carbaryl as an example, an exposure model, the Cumulative and Aggregate Risk Evaluation System (CARES), was used to generate time-concentration profiles for 500 virtual individuals exposed to carbaryl. These exposure profiles were used as inputs into a physiologically based pharmacokinetic (PBPK) model to predict urinary biomarker concentrations. These matching dietary intake levels and biomarker concentrations were used to (1) compare three reverse dosimetry approaches based on their ability to predict the central tendency of the intake dose distribution; and (2) identify parameters necessary for a more accurate exposure reconstruction. This study illustrates the trade-offs between using non-iterative reverse dosimetry methods that are fast, less precise and iterative methods that are slow, more precise. This study also intimates the necessity of including urine flow rate and elapsed time between last dose and urine sampling as part of the biomarker sampling collection for better interpretation of urinary biomarker data of short biological half-life chemicals. Resolution of these critical data gaps can allow exposure reconstruction methods to better predict population-level intake doses from large biomonitoring studies. PMID- 26545326 TI - Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves. AB - This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. PMID- 26545327 TI - Development of an inhalation unit risk factor for isoprene. AB - A unit risk factor (URF) was developed for isoprene based on evaluation of three animal studies with adequate data to perform dose-response modeling (NTP, 1994, 1999; Placke et al., 1996). Ultimately, the URF of 6.2E-08 per ppb (2.2E-08 per MUg/m(3)) was based on the 95% lower confidence limit on the effective concentration corresponding to 10% extra risk for liver carcinoma in male B6C3F1 mice after incorporating appropriate adjustment factors for species differences in target tissue metabolite concentrations and inhalation dosimetry. The corresponding lifetime air concentration at the 1 in 100,000 no significant excess risk level is 160 ppb (450 MUg/m(3)). This concentration is almost 4400 times lower than the lowest exposure level associated with statistically increased liver carcinoma in B6C3F1 mice in the key study (700 ppm in Placke et al., 1996) and is above typical isoprene breath concentrations reported in the scientific literature. Continuous lifetime environmental exposure to the 1 in 100,000 excess risk level of 160 ppb would be expected to raise the human blood isoprene area under the curve (AUC) less than one-third of the standard deviation of the endogenous mean blood AUC. The mean for ambient air monitoring sites in Texas (2005-2014) is approximately 0.13 ppb. PMID- 26545328 TI - [Elaboration and critical evaluation of clinical guidelines]. AB - Clinical guidelines are documents to help professionals and patients select the best diagnostic or therapeutic option. Elaborating guidelines requires an efficient literature search and a critical evaluation of the articles found to select the most appropriate ones. After that, the recommendations are formulated and then must be externally evaluated before they can be disseminated. Even when the guidelines are very thorough and rigorous, it is important to know whether they fulfill all the methodological requisites before applying them. With this aim, various scales have been developed to critically appraise guidelines. Of these, the AGREE II instrument is currently the most widely used. This article explains the main steps in elaborating clinical guidelines and the main aspects that should be analyzed to know whether the guidelines are well written. PMID- 26545329 TI - Magnetic resonance imaging for planning intracavitary brachytherapy for the treatment of locally advanced cervical cancer. AB - Cervical cancer is the third most common gynecological cancer. Its treatment depends on tumor staging at the time of diagnosis, and a combination of chemotherapy and radiotherapy is the treatment of choice in locally advanced cervical cancers. The combined use of external beam radiotherapy and brachytherapy increases survival in these patients. Brachytherapy enables a larger dose of radiation to be delivered to the tumor with less toxicity for neighboring tissues with less toxicity for neighboring tissues compared to the use of external beam radiotherapy alone. For years, brachytherapy was planned exclusively using computed tomography (CT). The recent incorporation of magnetic resonance imaging (MRI) provides essential information about the tumor and neighboring structures making possible to better define the target volumes. Nevertheless, MRI has limitations, some of which can be compensated for by fusing CT and MRI. Fusing the images from the two techniques ensures optimal planning by combining the advantages of each technique. PMID- 26545330 TI - [Persistent tunica vasculosa lentis]. PMID- 26545331 TI - Posterior segment involvement in cat-scratch disease: A case series. AB - INTRODUCTION: Cat-scratch disease (CSD) is a systemic infectious disease. The most well-known posterior segment presentation is neuroretinitis with a macular star. In this study, we present a case series emphasising the heterogeneity of the disease and the various posterior segment manifestations. MATERIALS AND METHODS: A retrospective case series of consecutive patients presenting with posterior segment CSD, over a 5-year period (2010 to 2015), at two ophthalmological centres in Midi-Pyrenees. RESULTS: Twelve patients (17 eyes) were included, of whom 11 (92%) presented with rapidly decreasing visual acuity, with 6 of these (50%) extremely abrupt. CSD was bilateral in 5 (42% of all patients). Posterior manifestations were: 12 instances of optic nerve edema (100%), 8 of focal chorioretinitis (67%) and only 6 of the classic macular edema with macular star (25% at first examination, but 50% later). Other ophthalmological complications developed in three patients; one developed acute anterior ischemic optic neuropathy, one a retrohyaloid hemorrhage and one a branch retinal artery occlusion, all secondary to occlusive focal vasculitis adjacent to focal chorioretinitis. CONCLUSION: Classical neuroretinitis with macular star is not the only clinical presentation of CSD. Practitioners should screen for Bartonella henselae in all patients with papillitis or focal chorioretinitis. PMID- 26545332 TI - No publication bias in industry funded clinical trials of degenerative diseases of the spine. AB - Industry sponsorship of clinical research of degenerative diseases of the spine has been associated with excessive positive published results as compared to research carried out without industry funding. We sought the rates of publication of clinical trials of degenerative diseases of the spine based on funding source as a possible explanation for this phenomenon. We reviewed all clinical trials registered at clinicaltrials.gov relating to degenerative diseases of the spine as categorized under six medical subject heading terms (spinal stenosis, spondylolisthesis, spondylolysis, spondylosis, failed back surgery syndrome, intervertebral disc degeneration) and with statuses of completed or terminated. These collected studies were categorized as having, or not having, industry funding. Published results for these studies were then sought within the clinicaltrials.gov database itself, PubMed and Google Scholar. One hundred sixty one clinical trials met these criteria. One hundred nineteen of these trials had industry funding and 42 did not. Of those with industry funding, 45 (37.8%) had identifiable results. Of those without industry funding, 17 (40.5%) had identifiable results. There was no difference in the rates of publication of results from clinical trials of degenerative diseases of the spine no matter the funding source. PMID- 26545333 TI - In-Membrane Chemical Modification (IMCM) for Site-Specific Chromophore Labeling of GPCRs. AB - We present in-membrane chemical modification (IMCM) for obtaining selective chromophore labeling of intracellular surface cysteines in G-protein-coupled receptors (GPCRs) with minimal mutagenesis. This method takes advantage of the natural protection of most cysteines by the membrane environment. Practical use of IMCM is illustrated with the site-specific introduction of chromophores for NMR and fluorescence spectroscopy in the human kappa-opioid receptor (KOR) and the human A2A adenosine receptor (A2A AR). IMCM is applicable to a wide range of in vitro studies of GPCRs, including single-molecule spectroscopy, and is a promising platform for in-cell spectroscopy experiments. PMID- 26545334 TI - The brain in bone and fuel metabolism. AB - Obesity and osteoporosis have become major public health challenges worldwide. The brain is well established as a pivotal regulator of energy homeostasis, appetite and fuel metabolism. However, there is now clear evidence for regulation between the brain and bone. Similarly, evidence also indicates that the involvement of the brain in bone and adipose regulation is both related and interdependent. The hypothalamus, with its semi-permeable blood brain barrier, is one of the most powerful regulatory regions within the body, integrating and relaying signals not only from peripheral tissues but also from within the brain itself. Two main neuronal populations within the arcuate nucleus of the hypothalamus regulate energy homeostasis: The orexigenic, appetite-stimulating neurons that co-express neuropeptide Y and agouti-related peptide and the anorexigenic, appetite-suppressing neurons that co-express proopiomelanocortin and cocaine- and amphetamine related transcript. From within the arcuate, these four neuropeptides encompass some of the most powerful control of energy homeostasis in the entire body. Moreover, they also regulate skeletal homeostasis, identifying a co-ordination network linking the processes of bone and energy homeostasis. Excitingly, the number of central neuropeptides and neural factors known to regulate bone and energy homeostasis continues to grow, with cannabinoid receptors and semaphorins also involved in bone homeostasis. These neuronal pathways represent a growing area of research that is identifying novel regulatory axes between the brain and the bone, and links with other homeostatic networks; thereby revealing a far more complex, and interdependent bone biology than previously envisioned. This review examines the current understanding of the central regulation of bone and energy metabolism. PMID- 26545335 TI - Effects of spaceflight on the murine mandible: Possible factors mediating skeletal changes in non-weight bearing bones of the head. AB - Spaceflight-induced remodeling of the skull is characterized by greater bone volume, mineral density, and mineral content. To further investigate the effects of spaceflight on other non-weight bearing bones of the head, as well as to gain insight into potential factors mediating the remodeling of the skull, the purpose of the present study was to determine the effects of spaceflight on mandibular bone properties. Female C57BL/6 mice were flown 15d on the STS-131 Space Shuttle mission (n=8) and 13d on the STS-135 mission (n=5) or remained as ground controls (GC). Upon landing, mandibles were collected and analyzed via micro-computed tomography for tissue mineralization, bone volume (BV/TV), and distance from the cemento-enamel junction to the alveolar crest (CEJ-AC). Mandibular mineralization was not different between spaceflight (SF) and GC mice for either the STS-131 or STS-135 missions. Mandibular BV/TV (combined cortical and trabecular bone) was lower in mandibles from SF mice on the STS-131 mission (80.7+/-0.8%) relative to that of GC (n=8) animals (84.2+/-1.2%), whereas BV/TV from STS-135 mice was not different from GC animals (n=7). The CEJ-AC distance was shorter in mandibles from STS-131 mice (0.217+/-0.004mm) compared to GC animals (0.283+/-0.009mm), indicating an anabolic (or anti-catabolic) effect of spaceflight, while CEJ-AC distance was similar between STS-135 and GC mice. These findings demonstrate that mandibular bones undergo skeletal changes during spaceflight and are susceptible to the effects of weightlessness. However, adaptation of the mandible to spaceflight is dissimilar to that of the cranium, at least in terms of changes in BV/TV. PMID- 26545336 TI - The role of CD40 and CD40L in bone mineral density and in osteoporosis risk: A genetic and functional study. AB - Compelling data are revealing that the CD40/CD40L system is involved in bone metabolism. Furthermore, we have previously demonstrated that polymorphisms in both genes are associated with bone phenotypes. The aim of this study is to further characterize this association and to identify the causal functional mechanism. We conducted an association study of BMD with 15 SNPs in CD40/CD40L genes in a population of 779 women. In addition, we assessed the functionality of this association through the study of the allele-dependent expression of CD40 and CD40L in peripheral blood leukocytes (PBLs) and in human osteoblasts (OBs) obtained from bone explants by qPCR and by sequencing. When an allelic imbalance (AI) was detected, studies on allele-dependent in vitro transcription rate and on CpG methylation in the gene promoter were also performed. Our results confirm the genetic association between SNP rs116535 (T>C) of CD40L gene with LS-BMD. Regarding CD40 gene, two SNPs showed nominal P-values<0.05 for FN- and LS-BMD (Z scores), although the association was not significant after correcting for multiple testing. Homozygous TT women for SNP rs1883832 (C>T) of CD40 gene showed a trend to have lower levels of OPG (Q-value=0.059), especially when women of BMD quartile ends were selected (P<0.05). Regarding functionality, we detected an AI for rs1883832 with the C allele the most expressed in OBs and in PBLs. Since the rs116535 of CD40L gene did not show AI, it was not further analyzed. Finally, we described a differential methylation of CpGs in the CD40 promoter among women of high in comparison to low BMD. Our results suggest that the CD40/CD40L system plays a role in regulating BMD. Effectively, our data suggest that a decreased production of OPG could be the cause of the lower BMD observed in TT women for rs1883832 of the CD40 gene and that the degree of methylation of CpGs in the CD40 promoter could contribute to the acquisition of BMD. One possibility that deserves further study is whether the degree of methylation of the CD40 gene affects the level of CD40 expression and, consequently, the level of OPG. PMID- 26545337 TI - Gas-phase simulated moving bed: Propane/propylene separation on 13X zeolite. AB - In the last years several studies were carried out in order to separate gas mixtures by SMB technology; however, this technology has never been implemented on an industrial scale. In the present work, a gas phase SMB bench unit was built and tested for the separation of propane and propylene mixtures, using 13X zeolite extrudates as adsorbent and isobutane as desorbent. Three experiments were performed to separate propane/propylene by gas phase SMB in the bench scale unit with a 4-2-2 configuration, i.e., open loop circuit by suppressing section IV (desorbent regeneration followed by a recycle). Consequently, all the experiments were conducted using an external supply of pure isobutane as desorbent. Parameters such as switching time, extract and raffinate stream flow rates were changed to improve the efficiency of the process. Experimental results have shown that it is feasible to separate propylene from propane by gas phase SMB at a bench scale and that this process is a potential candidate to replace the conventional technologies for the propane/propylene separation. The performance parameters obtained are very promising for future development of this technology, since propylene was obtained in the extract stream with a purity of 99.93%, a recovery of 99.51%, and a productivity of [Formula: see text] . Propane was obtained in the raffinate stream with a purity of 98.10%, a recovery of 99.73% and a productivity of [Formula: see text] . The success of the above mentioned bench scale tests is a big step for the future implementation of this technology in a larger scale. PMID- 26545338 TI - Residues of neonicotinoids and their metabolites in honey and pollen from sunflower and maize seed dressing crops. AB - A study was carried out to evaluate the possible presence of thiamethoxam, clothianidin and imidacloprid, as well as the metabolic breakdown products of these three neonicotinoids in pollen and honey obtained from brood chamber combs of honeybee colonies located next to sunflower and maize crops from coated seeds. Samples were analyzed by liquid chromatography coupled to quadrupole-time-of flight mass spectrometry detector, in combination with accurate mass tools such as diagnostic ions by exact mass, chlorine mass filters, and MS/MS experiments. The presence of thiamethoxam and clothianidin was confirmed in some of the pollen samples analyzed. Moreover, different metabolites of neonicotinoids were tentatively detected in the pollen and honey samples collected. The results suggested that four metabolites were found in the honey samples, while for pollen samples eleven metabolites were identified; among these, five were considered for the first time as metabolic breakdown products in sunflower and maize plants. PMID- 26545339 TI - Role of vision loss, functional limitations and the supporting network in depression in a general population. AB - PURPOSE: Although the prevalence of depression in visually impaired older persons is high, the association between vision loss and depression seems to be influenced by factors other than visual impairment. In this study, the role of vision loss, functional limitations and social network characteristics in relation to depressive symptoms was investigated. METHODS: Cross-sectional data (N = 1237) from the Longitudinal Aging Study Amsterdam were used to investigate the prevalence of depression (Center of Epidemiological Studies-Depression scale) within subgroups with increasing vision loss. In linear regression models, functional limitations and social network characteristics were examined as possible mediators in the association between vision loss and depression. Having a partner was considered to be a potential moderator. RESULTS: Although a significant linear trend was found in the presence of depressive symptoms with 14% in normally sighted, 23% in mild and 37% in severe vision loss (chi(2)(1) = 14.9; p < 0.001), vision loss was not an independent determinant of depression. Mediators were functional limitations (p < 0.001) and social network size (p = 0.009). No interaction with partner status was found. CONCLUSION: In the presence of depression, a trend was found with increasing severity of vision loss, indicating the need for more attention in (mental) health care and low-vision rehabilitation. In the general older population, vision loss was not an independent determinant of depression but was mediated by functional limitations and social network size. Rather than receiving actual social support, the idea of having a social network to rely on when needed seemed to be associated with lower levels of depression. PMID- 26545340 TI - Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. AB - Brain iron homeostasis is increasingly recognized as a potential target for the development of drug therapies for aging-related disorders. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. Indeed, many proteins initially characterized in those diseases such as amyloid-beta protein, alpha-synuclein, and huntingtin have been linked to iron neurochemistry. Iron plays a crucial role in maintaining normal physiological functions in the brain through its participation in many cellular functions such as mitochondrial respiration, myelin synthesis, and neurotransmitter synthesis and metabolism. However, excess iron is a potent source of oxidative damage through radical formation and because of the lack of a body-wide export system, a tight regulation of its uptake, transport and storage is crucial in fulfilling cellular functions while keeping its level below the toxicity threshold. In this review, we discuss the current knowledge on iron homeostasis in the brain and explore how alterations in brain iron metabolism affect neuronal function with emphasis on iron dysregulation in Alzheimer's and Parkinson's diseases. Finally, we discuss recent findings implicating iron as a diagnostic and therapeutic target for Alzheimer's and Parkinson's diseases. Iron plays a fundamental role in maintaining the high metabolic and energetic requirements of the brain. However, iron has to be maintained in a delicate balance as both iron overload and iron deficiency are detrimental to the brain and can trigger neurodegeneration. Here, we discuss the current knowledge on brain iron homeostasis and its involvement in major aging related neurodegenerative diseases. This article is part of a special issue on Parkinson disease. PMID- 26545341 TI - A Type of Auxiliary for Native Chemical Peptide Ligation beyond Cysteine and Glycine Junctions. AB - Native chemical ligation enables the chemical synthesis of proteins. Previously, thiol-containing auxiliary groups have been used to extend the reaction scope beyond N-terminal cysteine residues. However, the N-benzyl-type auxiliaries used so far result in rather low reaction rates. Herein, a new N(alpha) -auxiliary is presented. Consideration of a radical fragmentation for cleavage led to the design of a new auxiliary group which is selectively removed under mildly basic conditions (pH 8.5) in the presence of TCEP and morpholine. Most importantly and in contrast to previously described auxiliaries, the 2-mercapto-2-phenethyl auxiliary is not limited to Gly-containing sites and ligations succeed at sterically demanding junctions. The auxiliary is introduced in high yield by on resin reductive amination with commercially available amino acid building blocks. The synthetic utility of the method is demonstrated by the synthesis of two antimicrobial proteins, DCD-1L and opistoporin-2. PMID- 26545343 TI - Immediate post-traumatic pulmonary embolism is not associated with right ventricular dysfunction. AB - BACKGROUND: Post-traumatic pulmonary embolic events are associated with significant morbidity. Computed tomographic (CT) measurements can be predictive of right ventricular (RV) dysfunction after pulmonary embolus. However, it remains unclear whether these physiologic effects or clinical outcomes differ between early (<48 hours) vs late (>=48 hours) post-traumatic pulmonary embolism (PE). METHODS: All patients with traumatic injury and CT evidence of PE between 2008 and 2013 were identified. The study population was divided into 2 groups based on the time of diagnosis of the PE. The primary outcome was PE-related mortality. RESULTS: Fifty patients were identified (14 early PE and 36 late PE). Patients sustaining a late PE had a higher PE-related mortality rate (16.7% vs 0%), larger RV diameters, RV/left ventricular diameter ratios, RV volumes, and RV/left ventricular volume ratios (all P < .05). CONCLUSIONS: Early post traumatic PE appears to be associated with fewer RV physiologic changes than late post-traumatic PE and may be representative of primary pulmonary thrombosis. It remains to be seen whether early CT findings of PE should be managed according to previously established guidelines for embolic disease. PMID- 26545342 TI - Disruption of Spinal Noradrenergic Activation Delays Recovery of Acute Incision Induced Hypersensitivity and Increases Spinal Glial Activation in the Rat. AB - Results of clinical studies suggest that descending inhibitory controls from the brainstem are important for speeding recovery from pain after surgery. We examined the effects of destroying spinally projecting noradrenergic neurons via intrathecally administered antibody to dopamine beta-hydroxylase conjugated to saporin (DbetaH-saporin) on recovery in an acute incisional pain model. Mechanical and thermal paw withdrawal thresholds and nonevoked spontaneous guarding scores were tested for several weeks postoperatively and analyzed using mixed effects growth curve modeling. DbetaH-saporin treatment resulted in a significant prolongation in the duration of mechanical and to a lesser degree thermal hypersensitivity in the ipsilateral paw of incised rats but did not increase the duration of spontaneous guarding. DbetaH-saporin treatment was also associated with increased microglial and astrocyte activation in the ipsilateral spinal cord 21 days after incision compared with immunoglobulin G-saporin treated controls. Chronic intrathecal administration of the alpha2 adrenergic receptor antagonist atipamezole (50-200 MUg/d) produced similar effects. These data suggest that spinally projecting noradrenergic pathways and spinal alpha2 adrenergic receptor activation are important for speeding recovery from hypersensitivity after surgical incision possibly by reducing spinal glial activation. Interventions that augment the noradrenergic system might be important to speed recovery from pain after surgery. PERSPECTIVE: Endogenous descending spinal noradrenergic activation promotes resolution of incision induced hypersensitivity and inhibits spinal microglial and astrocyte activation in part through alpha2 adrenergic receptors. PMID- 26545345 TI - Racial and age disparities persist in immediate breast reconstruction: an updated analysis of 48,564 patients from the 2005 to 2011 American College of Surgeons National Surgery Quality Improvement Program data sets. AB - BACKGROUND: Immediate breast reconstruction (IBR) rates continue to rise, yet recent patterns based on race, age, and patient comorbidities have not been adequately assessed. METHODS: Women undergoing mastectomy only or mastectomy with IBR from 2005 to 2011 were identified in the American College of Surgeons National Surgical Quality Improvement (NSQIP) data sets. A multivariate logistic regression was performed to determine factors independently associated with receipt of IBR. Thirty-day surgical complication rates after IBR were also assessed. RESULTS: Rates of IBR increased significantly over the study period from 26% of patients in 2005 to 40% in 2011. Non-Caucasian race, older age (>=45 years), obesity, and presence of comorbid conditions including diabetes mellitus, current smoking, and cardiovascular disease were all negatively associated with receipt of IBR. Surgical complication rates after IBR were not predicted by non Caucasian race, older age, or presence of diabetes mellitus. CONCLUSIONS: This current assessment of IBR using the American College of Surgeons-National Surgical Quality Improvement data sets demonstrates that non-Caucasian and older women (>=45 years) continue to receive IBR at lower rates despite the lack of association of added risk of surgical morbidity. PMID- 26545344 TI - Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost. AB - BACKGROUND: Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. METHODS: A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. RESULTS: From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. CONCLUSIONS: Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. PMID- 26545346 TI - Comparison of dental and alveolar arch forms between different ethnic groups. AB - OBJECTIVE: The aims of this study were to evaluate, by means of 3D software, any correlation between ethnic group and the shape and size of the dental arcade and its bony support, and to investigate the correspondence between the latter two variables within each ethnic group. The data gathered were also compared with the measurements of commercially available pre-formed archwires to determine which provide the best fit for each arch in each group. MATERIALS AND METHODS: The shape and size of the dental and alveolar arches of 29 subjects of African origin and 37 Caucasian subjects were compared in terms of linear inter-canine, inter premolar and inter-molar measurements, overall arch length, and the distance between each tooth and the reference occlusal plane. To determine which pre formed archwires are best suited to each of the two ethnic groups, the in-out of the brackets was considered, simulating their presence in the oral cavity. RESULTS: The upper and lower dental and alveolar arches were all wider and longer in African with respect to Caucasian subjects (P<0.05). In general, "Roth small" (index value 1.556) and "Ideal Form Medium" (index value 0.645) archwires were better suited to both upper and lower arcades in the latter group, while "Damon" (index value 1.447) and "Ideal Form Large" (index value 1.695) conformed better to the size and shape of both arcades in the former. CONCLUSIONS: There are very significant differences in arch form between the two ethnic groups considered, and the range of pre-formed archwires on the market does not provide for the anatomical variability of patients. PMID- 26545348 TI - Augmentation of the alveolar ridge compared with shorter implants in atrophic jaws: a meta-analysis based on randomised controlled trials. AB - Our aim was to compare two therapeutic options--augmentation of the alveolar ridge and shorter implants--in the treatment of atrophic jaws. To fulfill the preset inclusion criteria, we searched the electronic databases PubMed, EMBASE through OVID, and the Cochrane Central Register of Controlled Trials (CENTRAL). Two people were responsible for screening, extraction of data, and assessment of quality. The meta-analysis was made with the aid of Review Manager (RevMan) 5.1. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). The electronic database and manual search yielded 1426 studies. After screening the titles, abstract, and the full text, and cross-matched them with the inclusion criteria, only 6 studies were eligible. A total of 837 implants were investigated, which included 429 in the augmentation group and 408 in the shorter implants group. There were significantly more failed implants (p=0.006), complications (p=0.01), and marginal bone losses (p=0.0004) in the augmentation group than in the shorter implants group. According to the GRADE, the levels of evidence were moderate (failed implants), high (complication rate), and high (loss of alveolar bone). In atrophic jaws with enough residual bone, shorter implants without augmentation might be the first choice as they seem to be associated with fewer failed implants and complications, and less peri-implant bone loss. PMID- 26545350 TI - Counting the cost of child mortality in the World Health Organization African region. AB - BACKGROUND: Worldwide, a total of 6.282 million deaths occurred among children aged less than 5 years in 2013. About 47.4 % of those were borne by the 47 Member States of the World Health Organization (WHO) African Region. Sadly, even as we approach the end date for the 2015 Millennium Development Goals (MDGs), only eight African countries are on track to achieve the MDG 4 target 4A of reducing under-five mortality by two thirds between 1990 and 2015. The post-2015 Sustainable Development Goal (SDG) 3 target is "by 2030, end preventable deaths of new-borns and children under 5 years of age". There is urgent need for increased advocacy among governments, the private sector and development partners to provide the resources needed to build resilient national health systems to deliver an integrated package of people-centred interventions to end preventable child morbidity and mortality and other structures to address all the basic needs for a healthy population. The specific objective of this study was to estimate expected/future productivity losses from child deaths in the WHO African Region in 2013 for use in advocacy for increased investments in child health services and other basic services that address children's welfare. METHODS: A cost-of illness method was used to estimate future non-health GDP losses related to child deaths. Future non-health GDP losses were discounted at 3 %. The analysis was undertaken with the countries categorized under three income groups: Group 1 consisted of nine high and upper middle income countries, Group 2 of 13 lower middle income countries, and Group 3 of 25 low income countries. One-way sensitivity analysis at 5 % and 10 % discount rates assessed the impact of the expected non-health GDP loss. RESULTS: The discounted value of future non-health GDP loss due to the deaths of children under 5 years old in 2013 will be in the order of Int$ 150.3 billion. Approximately 27.3 % of the loss will be borne by Group 1 countries, 47.1 % by Group 2 and 25.7 % by Group 3. The average non health GDP lost per child death will be Int$ 174 310 for Group 1, Int$ 57 584 for Group 2 and Int$ 25 508 for Group 3. CONCLUSIONS: It is estimated that the African Region will incur a loss of approximately 6 % of its non-health GDP from the future years of life lost among the 2 976 000 child deaths that occurred in 2013. Therefore, countries and development partners should in solidarity sustainably provide the resources essential to build resilient national health systems and systems to address the determinants of health and meet the other basic needs such as for clothing, education, food, shelter, sanitation and clean water to end preventable child morbidity and mortality. PMID- 26545349 TI - Insm1 promotes neurogenic proliferation in delaminated otic progenitors. AB - INSM1 is a zinc-finger protein expressed throughout the developing nervous system in late neuronal progenitors and nascent neurons. In the embryonic cortex and olfactory epithelium, Insm1 may promote the transition of progenitors from apical, proliferative, and uncommitted to basal, terminally-dividing and neuron producing. In the otocyst, delaminating and delaminated progenitors express Insm1, whereas apically-dividing progenitors do not. This expression pattern is analogous to that in embryonic olfactory epithelium and cortex (basal/subventricular progenitors). Lineage analysis confirms that auditory and vestibular neurons originate from Insm1-expressing cells. In the absence of Insm1, otic ganglia are smaller, with 40% fewer neurons. Accounting for the decrease in neurons, delaminated progenitors undergo fewer mitoses, but there is no change in apoptosis. We conclude that in the embryonic inner ear, Insm1 promotes proliferation of delaminated neuronal progenitors and hence the production of neurons, a similar function to that in other embryonic neural epithelia. Unexpectedly, we also found that differentiating, but not mature, outer hair cells express Insm1, whereas inner hair cells do not. Insm1 is the earliest known gene expressed in outer versus inner hair cells, demonstrating that nascent outer hair cells initiate a unique differentiation program in the embryo, much earlier than previously believed. PMID- 26545353 TI - Characterization and functional analysis of Trichinella spiralis Nudix hydrolase. AB - Trichinella spiralis Nudix hydrolase (TsNd) was identified by screening a T7 phage display cDNA library from T. spiralis intestinal infective larvae (IIL), and vaccination of mice with recombinant TsNd protein (rTsNd) or TsNd DNA vaccine produced a partial protective immunity. The aim of this study was to identify the characteristics and biological functions of TsNd in the process of invasion and development of T. spiralis larvae. Transcription and expression of TsNd gene at all developmental stages of T. spiralis were observed by qPCR and immunofluorescent test (IFT). The rTsNd had the Nd enzymatic activity to dGTP, NAD, NADP and CoA. Its kinetic properties on the preferred substrate dGTP were calculated, and the Vmax, Km, and kcat/Km values at pH 8.0 were 3.19 MUM min(-1) MUg(-1), 370 MUM, and 144 s(-1) M(-1), respectively, in reaction matrix containing 5 mM Zn(2+) and 2 mM DTT. The rTsNd was active from 25 degrees C to 50 degrees C, with optimal activity at 37 degrees C. rTsNd was able to bind specifically to mouse intestinal epithelial cells (IECs) and promoted the larval invasion of IECs, whereas anti-rTsNd antibodies inhibited the larval invasion of IECs in a dose-dependent manner. Anti-rTsNd antibodies could kill T. spiralis infective larvae by an ADCC-mediated mechanism. Our results showed that the rTsNd protein was able to interact with host IECs, had the Nudix hydrolasing activity and the enzymatic activity appeared to be essential indispensable for the T. spiralis larval invasion, development and survival in host. PMID- 26545354 TI - Synthesis, characterization, DNA interactions, DNA cleavage, radical scavenging activity, antibacterial, anti-proliferative and docking studies of new transition metal complexes. AB - The compound N-(2-hydroxybenzylidene)-1-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8 naphthyridine-3-carbohydrazide (LH) and its Cu (II), Co (II) and Zn (II) complexes were synthesized and characterized. The absorption spectral titrations and competitive DNA binding studies depicted those complexes of title compound bind to CT-DNA through intercalation. Interestingly [Cu (II)-(L2)] showed relatively high binding constant value (6.61 x 10(5) M(-1)) compared to [Co (II) (L2)] (4.378* 10(5) M(-1)) and [Zn (II)-(L2)] (3.1x10(5) M(-1)). Ligand and its complexes were also examined for DNA nuclease activity against pBR-322 plasmid DNA, which showed that [Cu (II)-(L2)] had the best hydrolytic cleavage property displaying prominent double-strand DNA cleavage. In addition, antioxidant activities of the ligand and its metal complexes investigated through scavenging effects for DPPH radical in- vitro, indicated their potentiality as good antioxidants. The in vitro anti-bacterial study inferred the better anti bacterial activity of [Cu (II)-(L2)] and this was also correlated theoretically by employing docking studies wherein [Cu (II)-(L2)] displayed good Gold score and Chem score. Finally the in vitro anti- proliferative activity of studied compounds was tested against HeLa and MCF-7 cell lines. Interestingly [Cu (II) (L2)] displayed lower IC50 value and lower percentage of viability in both HeLa and MCF-7 cell lines. PMID- 26545355 TI - A Chromone-Derived Schiff-Base Ligand as Al(3+) "Turn on" Fluorescent Sensor: Synthesis and Spectroscopic Properties. AB - In this study, a novel chromone-derived Schiff-base ligand called 6-Hydroxy-3 formylchromone (2'-furan formyl) hydrazone (HCFH) has been designed and synthesized as a "turn on" fluorescent sensor for Al(3+). This sensor HCFH showed high selectivity and sensitivity towards Al(3+) over other metal ions investigated, and most metal ions had nearly no influences on the fluorescence response of HCFH to Al(3+). Additionally, the significant enhancement by about 171-fold in fluorescence emission intensity at 502 nm was observed in the presence of Al(3+) in ethanol, and it was due to the chelation-enhanced fluorescence (CHEF) effect upon complexation of HCFH with Al(3+) which inhibited the photoinduced electron transfer (PET) phenomenon from the Schiff-base nitrogen atom to chromone group. Moreover, this sensor formed a 1 : 1 complex with Al(3+) and the fluorescence response of HCFH to Al(3+) was nearly completed within 1 min. Thus, this sensor HCFH could be used to detect and recognize Al(3+) for real time detection. PMID- 26545356 TI - On the transmission dynamics of Buruli ulcer in Ghana: Insights through a mathematical model. AB - BACKGROUND: Mycobacterium ulcerans is know to cause the Buruli ulcer. The association between the ulcer and environmental exposure has been documented. However, the epidemiology of the ulcer is not well understood. A hypothesised transmission involves humans being bitten by the water bugs that prey on mollusks, snails and young fishes. METHODS: In this paper, a model for the transmission of Mycobacterium ulcerans to humans in the presence of a preventive strategy is proposed and analysed. The model equilibria are determined and conditions for the existence of the equilibria established. The model analysis is carried out in terms of the reproduction number [Formula: see text]. The disease free equilibrium is found to be locally asymptotically stable for [Formula: see text] The model is fitted to data from Ghana. RESULTS: The model is found to exhibit a backward bifurcation and the endemic equilibrium point is globally stable when [Formula: see text] Sensitivity analysis showed that the Buruli ulcer epidemic is highly influenced by the shedding and clearance rates of Mycobacterium ulcerans in the environment. The model is found to fit reasonably well to data from Ghana and projections on the future of the Buruli ulcer epidemic are also made. CONCLUSIONS: The model reasonably fitted data from Ghana. The fitting process showed data that appeared to have reached a steady state and projections showed that the epidemic levels will remain the same for the projected time. The implications of the results to policy and future management of the disease are discussed. PMID- 26545357 TI - Non-tuberculous mycobacteria (NTM) in Zambia: prevalence, clinical, radiological and microbiological characteristics. AB - BACKGROUND: Non-tuberculous mycobacteria (NTM) infection is an emerging health problem. We present here the Zambia-specific national level data of prevalence, symptomatic, radiological and microbiological characteristics of NTM, using results from a national Tuberculosis (TB) prevalence survey. METHODS: This was a cross-sectional study of the prevalence of NTM among adults aged 15 years and above, who were participants in a national TB prevalence survey. Participants who had either an abnormal chest x-ray or were symptomatic were considered presumptive TB cases and submitted sputum for smear and culture analysis. HIV testing was performed on an opt-out basis. Symptomatic NTM prevalence was estimated from individual level analysis. RESULTS: Of the 6,123 individuals with presumptive TB, 923 (15.1%) were found to have NTM, 13 (0.2%) were MTB/NTM co infected and 338 (5.5%) were contaminated (indeterminate). The prevalence of symptomatic NTM was found to be 1,477/100,000 [95% CI 1010-1943]. Smear positivity, history of cough or chest pain and HIV positivity were risk factors for NTM. CONCLUSION: This first study to estimate the national prevalence of NTM in Zambia indicates that the burden is high. The NTM occurrence in Zambia constitutes both a public health and ethical issue requiring action from health managers. PMID- 26545358 TI - Mycobacterium alsense sp. nov., a scotochromogenic slow grower isolated from clinical respiratory specimens. AB - The name 'Mycobacterium alsiense', although reported in 2007, has not been validly published. Polyphasic characterization of three available strains of this species led us to the conclusion that they represent a distinct species within the genus Mycobacterium. The proposed novel species grows slowly and presents pale yellow-pigmented colonies. Differentiation from other mycobacteria is not feasible on the basis of biochemical and cultural features alone while genetic analysis, extended to eight housekeeping genes and one spacer region, reveals its clear distinction from all other mycobacteria. Mycobacterium asiaticum is the most closely related species on the basis of 16S rRNA gene sequences (similarity 99.3 %); the average nucleotide identity between the genomes of the two species is 80.72 %, clearly below the suggested cut-off (95-96 %). The name Mycobacterium alsense sp. nov. is proposed here for the novel species and replaces the name 'M. alsiense', ex Richter et al. 2007, given at the time of isolation of the first strain. The type strain is TB 1906T ( = DSM 45230T = CCUG 56586T). PMID- 26545359 TI - Partitioning, duality, and linkage disequilibria in the Moran model with recombination. AB - The multilocus Moran model with recombination is considered, which describes the evolution of the genetic composition of a population under recombination and resampling. We investigate a marginal ancestral recombination process, where each site is sampled only in one individual and we do not make any scaling assumptions in the first place. Following the ancestry of these loci backward in time yields a partition-valued Markov process, which experiences splitting and coalescence. In the diffusion limit, this process turns into a marginalised version of the multilocus ancestral recombination graph. With the help of an inclusion-exclusion principle and so-called recombinators we show that the type distribution corresponding to a given partition may be represented in a systematic way by a sampling function. The same is true of correlation functions (known as linkage disequilibria in genetics) of all orders. We prove that the partitioning process (backward in time) is dual to the Moran population process (forward in time), where the sampling function plays the role of the duality function. This sheds new light on the work of Bobrowski et al. (J Math Biol 61:455-473, 2010). The result also leads to a closed system of ordinary differential equations for the expectations of the sampling functions, which can be translated into expected type distributions and expected linkage disequilibria. PMID- 26545360 TI - Prognostic significance of classified extramural tumor deposits and extracapsular lymph node invasion in T3-4 colorectal cancer: a retrospective single-center study. AB - BACKGROUND: Extramural tumor deposits (TDs) and extracapsular lymph node involvement (ECLNI) are considered to be poor prognostic factors in patients with T3-4, N0-2, M0 colorectal cancer (CRC). Although TDs are known to have multiple origins and pleomorphic features, the prognostic significances of the different type of TDs have not yet been established. METHODS: We performed a retrospective review of 385 consecutive patients with T3-4, N0-2, M0 CRC who received curative resection at our institution between 2006 and 2012. We classified the TDs into two groups: invasive-type TD (iTD), which is characterized by the presence of lymphatic invasion, vascular invasion, perineural invasion, or undefined cancer cell clusters and nodular-type TD (nTD), which is characterized by a smooth or irregular-shaped tumor nodule other than an iTD. ECLNI was defined as invasion of cancer cells into capsular collagen tissues or adipose tissues beyond the capsular collagen. Multivariate analyses were used to assess the prognostic significance of iTD, ND, and ECLNI for relapse-free survival (RFS), disease specific survival (DSS), and sites of recurrence. RESULTS: In patients without lymph node (LN) metastasis, the incidences of iTD and nTD were both in the range of 2-3 %. Conversely, in patients with LN metastasis, the incidences of iTD, nTD, and ECLNI were 31, 22, and 34 %, respectively. iTD, nTD, and ECLNI were all significant independent adverse factors for RFS in rectal cancer, and were all associated with pT, pN, and LN ratio. iTD was a significant independent adverse prognostic factor for DSS in rectal cancer, metastasis to the liver in colorectal cancer, and distant LN metastasis in colon cancer. ECLNI was a significant independent prognostic factor for RFS in colon cancer. CONCLUSIONS: Classifying TDs and assessing ECLNI may help establish significant prognostic factors for patients with T3-4, N0-2, M0 CRC. PMID- 26545361 TI - Living scaffolds: surgical repair using scaffolds seeded with human adipose derived stem cells. AB - BACKGROUND: Decellularized porcine small intestinal submucosa (SIS) is a biological scaffold used surgically for tissue repair. Here, we demonstrate a model of SIS as a scaffold for human adipose-derived stem cells (ASCs) in vitro and apply it in vivo in a rat ventral hernia repair model. STUDY DESIGN: ASCs adherence was examined by confocal microscopy and proliferation rate was measured by growth curves. Multipotency of ASCs seeded onto SIS was tested using adipogenic, chondrogenic, and osteogenic induction media. For in vivo testing, midline abdominal musculofascial and peritoneal defects were created in Sprague Dawley rats. Samples were evaluated for tensile strength, histopathology and immunohistochemistry. RESULTS: All test groups showed cell adherence and proliferation on SIS. Fibronectin-treated scaffolds retained more cells than those treated with vehicle alone (p < 0.05). Fresh stromal vascular fraction (SVF) pellets containing ASCs were injected onto the SIS scaffold and showed similar results to cultured ASCs. Maintenance of multipotency on SIS was confirmed by lineage-specific markers and dyes. Histopathology revealed neovascularization and cell influx to ASC-seeded SIS samples following animal implantation. ASC-seeded SIS appeared to offer a stronger repair than plain SIS, but these results were not statistically significant. Immunohistochemistry showed continued presence of cells of human origin in ASC-seeded repairs at 1 month postoperation. CONCLUSION: Pretreatment of the scaffold with fibronectin offers a method to increase cell adhesion and delivery. ASCs maintain their immunophenotype and ability to differentiate while on SIS. Seeding freshly isolated SVF onto the scaffold demonstrated that minimally manipulated cells may be useful for perioperative surgical applications within the OR suite. We have shown that this model for a "living mesh" can be successfully used in abdominal wall reconstruction. PMID- 26545362 TI - Effects of Resistance Training on Lower-Extremity Muscle Power in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Resistance training (RT) has been investigated as a potential intervention strategy for improving muscle function, but the effects on lower extremity muscle power in middle-aged and older adults have not been systematically reviewed. OBJECTIVE: The aim of this meta-analysis is to provide a quantitative estimate of the effect of RT on lower-extremity muscle power in middle-aged and older adults and to examine independent moderators of this relationship. METHODS: Randomized controlled trials that examined the effects of RT on either leg press (LP) or knee extension (KE) muscle power in adults aged >=50 years were included. Data were aggregated with meta-analytic techniques, and multi-level modeling was used to adjust for nesting effects. A total of 52 effects from 12 randomized controlled trials were analyzed with a random-effects model to estimate the effect of RT on lower-extremity muscle power. A multiple regression analysis was conducted to examine independent moderators of the mean effect. RESULTS: The adjusted aggregated results from all studies indicate that RT has a small-to-moderate effect on lower-extremity muscle power (Hedges' d = 0.34, 95% confidence interval [CI] 0.25-0.43), which translated to 54.90 watts (95 % CI 40.37-69.43). Meta-regression analyses indicated that high-velocity RT was superior to traditional RT (Delta = 0.62 vs. 0.20, respectively) for increasing lower-extremity muscle power. In addition, training volume significantly moderated the effect of RT on muscle power. CONCLUSION: The findings from this meta-analysis indicate that RT is an efficacious intervention strategy for improving LP and KE muscle power in adults aged >=50 years. Training mode and volume independently moderate the effect of RT on lower-extremity muscle power, and should be considered when prescribing RT exercise for middle-aged and older adults. PMID- 26545363 TI - The Influence of Head Impact Threshold for Reporting Data in Contact and Collision Sports: Systematic Review and Original Data Analysis. AB - BACKGROUND: Head impacts and resulting head accelerations cause concussive injuries. There is no standard for reporting head impact data in sports to enable comparison between studies. OBJECTIVE: The aim was to outline methods for reporting head impact acceleration data in sport and the effect of the acceleration thresholds on the number of impacts reported. METHODS: A systematic review of accelerometer systems utilised to report head impact data in sport was conducted. The effect of using different thresholds on a set of impact data from 38 amateur senior rugby players in New Zealand over a competition season was calculated. RESULTS: Of the 52 studies identified, 42% reported impacts using a >10-g threshold, where g is the acceleration of gravity. Studies reported descriptive statistics as mean +/- standard deviation, median, 25th to 75th interquartile range, and 95th percentile. Application of the varied impact thresholds to the New Zealand data set resulted in 20,687 impacts of >10 g, 11,459 (45% less) impacts of >15 g, and 4024 (81% less) impacts of >30 g. DISCUSSION: Linear and angular raw data were most frequently reported. Metrics combining raw data may be more useful; however, validity of the metrics has not been adequately addressed for sport. Differing data collection methods and descriptive statistics for reporting head impacts in sports limit inter-study comparisons. Consensus on data analysis methods for sports impact assessment is needed, including thresholds. Based on the available data, the 10-g threshold is the most commonly reported impact threshold and should be reported as the median with 25th and 75th interquartile ranges as the data are non-normally distributed. Validation studies are required to determine the best threshold and metrics for impact acceleration data collection in sport. CONCLUSION: Until in-field validation studies are completed, it is recommended that head impact data should be reported as median and interquartile ranges using the 10-g impact threshold. PMID- 26545364 TI - Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia. AB - BACKGROUND: Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown. FINDINGS: In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited. CONCLUSION: Our findings reveal that the lncRNA PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management. PMID- 26545365 TI - MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down regulation of GADD45alpha. AB - BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45alpha down regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45alpha expression in a xenograft model. Consistently, the knockdown of GADD45alpha expression partially neutralized the effects of miR-362 5p inhibition. Furthermore study suggested that GADD45alpha mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45alpha, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets. PMID- 26545366 TI - Tuscan black kale sprout extract bioactivated with myrosinase: a novel natural product for neuroprotection by inflammatory and oxidative response during cerebral ischemia/reperfusion injury in rat. AB - BACKGROUND: Cerebral ischemia and reperfusion (CIR) is a pathological condition characterized by a first blood supply restriction to brain followed by the consequent restoration of blood flow and simultaneous reoxygenation. The aim of this study was to evaluate the neuroprotective effects of Tuscan black kale sprout extract (TBK-SE) bioactivated with myrosinase enzyme, assessing its capability to preserve blood-brain barrier (BBB), in a rat model of CIR. METHODS: CIR was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. RESULTS: By immunohistochemical evaluation and western blot analysis of brain and cerebellum tissues, our data have clearly shown that administration of bioactive TBK-SE is able to restore alterations of tight junction components (claudin-5 immunolocalization). Also, bioactive TBK-SE reduces some inflammatory key-markers (p-selectin, GFAP, Iba-1, ERK1/2 and TNF-alpha), as well as the triggering of neuronal apoptotic death pathway (data about Bax/Bcl-2 balance, p53 and cleaved caspase 3) and the generation of radicalic species by oxidative stress (results focused on iNOS, nitrotyrosine and Nrf2). CONCLUSION: Taken together, our findings lead to believe that bioactive TBK-SE exerts pharmacological properties in protecting BBB integrity through a mechanism of action that involves a modulation of inflammatory and oxidative pathway as well into control of neuronal death. PMID- 26545367 TI - The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage. AB - BACKGROUND: Activated prothrombin complex concentrates factor eight inhibitor bypassing activity (FEIBA) has been recommended for reversing novel oral anticoagulants (NOAC) in the context of intracerebral hemorrhage (ICH), though few clinical studies report its use. METHODS: A prospective study of patients with spontaneous ICH was conducted from May 2013 to May 2015. Hospital complications including hemorrhage (gastrointestinal bleeding, anemia requiring transfusion, and surgical site bleeding) and thrombosis (pulmonary embolus, deep vein thrombosis, ischemic stroke, and myocardial infarction) were recorded. All ICH patients underwent baseline head CT and a follow-up stability scan in 6 h. NOAC taken within 48 h of presentation was reversed with FEIBA (50 u/kg) per protocol. Three-month outcomes were assessed using the modified rankin score (mRS). RESULTS: Of 127 ICH patients enrolled, 6 (5 %) had NOAC-related ICH including: oral factor XA inhibitor N = 5 (4 %; N = 4 rivaroxaban, N = 1 apixaban] and direct thrombin inhibitor N = 1 (0.8 %; dabigatran). The indication for NOAC was atrial fibrillation in all patients and the median CHADS2-VASC score was 4 (range 2-5). The median admission NIHSS was 2 (range 0-14) and the median ICH volume was 8 mL (range 1-20). Five patients (3 rivaroxaban, 1 apixaban, 1 dabigatran) presented within 48 h and received FEIBA within a median of 13 h (range 10-29 h) from their last NOAC dose and 8 h (range 4.5-20) from the time last known well. None of the patients had ICH expansion, hemorrhagic, or thrombotic complications. Three-month median mRS was 1 (range 0-6). CONCLUSION: In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications. PMID- 26545368 TI - Network analysis of microRNA and mRNA seasonal dynamics in a highly plastic sensorimotor neural circuit. AB - BACKGROUND: Adult neurogenesis and the incorporation of adult-born neurons into functional circuits requires precise spatiotemporal coordination across molecular networks regulating a wide array of processes, including cell proliferation, apoptosis, neurotrophin signaling, and electrical activity. MicroRNAs (miRs) - short, non-coding RNA sequences that alter gene expression by post transcriptional inhibition or degradation of mRNA sequences - may be involved in the global coordination of such diverse biological processes. To test the hypothesis that miRs related to adult neurogenesis and related cellular processes are functionally regulated in the nuclei of the avian song control circuit, we used microarray analyses to quantify changes in expression of miRs and predicted target mRNAs in the telencephalic nuclei HVC, the robust nucleus of arcopallium (RA), and the basal ganglia homologue Area X in breeding and nonbreeding Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelli). RESULTS: We identified 46 different miRs that were differentially expressed across seasons in the song nuclei. miR-132 and miR-210 showed the highest differential expression in HVC and Area X, respectively. Analyzing predicted mRNA targets of miR-132 identified 33 candidate target genes that regulate processes including cell cycle control, calcium signaling, and neuregulin signaling in HVC. Likewise, miR-210 was predicted to target 14 mRNAs differentially expressed across seasons that regulate serotonin, GABA, and dopamine receptor signaling and inflammation. CONCLUSIONS: Our results identify potential miR-mRNA regulatory networks related to adult neurogenesis and provide opportunities to discover novel genetic control of the diverse biological processes and factors related to the functional incorporation of new neurons to the adult brain. PMID- 26545370 TI - Combined effect of proton-pump inhibitors and other drugs with regard to lower gastrointestinal tract bleeding with special reference to low-dose aspirin. PMID- 26545369 TI - Targeting inflammation to influence mood following spinal cord injury: a randomized clinical trial. AB - BACKGROUND: The purpose of the present study was to examine the efficacy of targeting inflammation as a means of improving mood following spinal cord injury (SCI) and explore the potential mechanisms of action. METHODS: The study was a randomized, parallel-group, controlled, clinical trial (NCT02099890) whereby 20 participants with varying levels and severities of SCI were randomized (3:2) to either the treatment group, consisting of a 12-week anti-inflammatory diet, or control group. Outcome measures were assessed at baseline, 1 and 3 months, and consisted of CES-D scores of depression, markers of inflammation as assessed by various pro- and anti-inflammatory cytokines and several amino acids related to depression. RESULTS: A significant group * time interaction was found for CES-D (Center for Epidemiologic studies Depression Scale) score (p = 0.01), the TRP/LNAA (tryptophan/large neutral amino acid) ratio (p = 0.04), the composite score of pro-inflammatory cytokines (p = 0.04), IL-1beta (interleukin-1 beta) (p = 0.04), and IFN-gamma (interferon gamma) (p = 0.03). Pearson's r correlation showed significance between the ?IL-1beta and both the ?CES-D score (r = 0.740, p < 0.01) and the ?KYN/TRP (kynurenine/tryptophan) ratio (r = 0.536, p = 0.02). The ?KYN/TRP ratio was also significantly correlated with the ?CES-D score (r = 0.586, p = 0.01). Mediation analysis showed that the relationship between the ?KYN/TRP ratio and the ?CES-D score was mediated by the ?IL-1beta. Subgroup analysis showed that participants with high CES-D scores had significantly higher concentrations of IL-1beta, and all correlations were maintained or strengthened within this subgroup. CONCLUSIONS: Overall, the results demonstrated the effectiveness of targeting inflammation as a means of improving mood in SCI, with potential mechanisms relating to the reduction in IL-1beta and improvements in levels of neuroactive compounds related to the kynurenine pathway. Due to the limited sample size, results should be interpreted with caution; however, they are worthy of further examination due to the potential impact of inflammation on depression. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02099890 . PMID- 26545371 TI - Assessment of metal contamination in groundwater and soils in the Ahangaran mining district, west of Iran. AB - In this study, 28 groundwater and 13 soil samples from Ahangaran mining district in Hamedan Province, west of Iran were collected to evaluate the level of contamination. Average concentrations of As, Cu, Pb, Zn, Mn, Sb, and Ni in groundwater samples were 1.39, 3.73, 2.18, 9.37, 2.35, 4.44, and 5.50 MUg/L (wet season), and 11.64, 4.92, 4.32, 14.77, 5.43, 4.12, and 0.98 MUg/L (dry season), respectively. Results of groundwater samples analysis showed that the average of analyzed metals in the wet and dry seasons were below the permissible limits, except As in the dry season which displays concentrations that exceed US EPA water quality criteria recommended for drinking water. Also, the heavy metal pollution index (HPI) values in each sampling station were less than the critical index limit and were suitable for drinking. Factor analysis revealed that variables influential to groundwater quality in one season may not be as important in another season. Average concentrations of Ag, As, Cd, Cu, Pb, Sb, and Zn in soil samples were 2.61, 31.44, 0.51, 55.90, 1284.9, 21.26, and 156.04 mg kg(-1), respectively. The results of the geoaccumulation index (I geo) showed the following decreasing order: Pb > Zn > Cu > As > Sb > Cd > Ag. Potential ecological risk index (RI) suggests that the contamination in the investigated area is moderate to very high risk and the ranking of the contaminants in decreasing order is Ag > Sb > Pb > Cd > As > Cu > Zn. PMID- 26545372 TI - Assessment of the climate change impacts on fecal coliform contamination in a tidal estuarine system. AB - Climate change is one of the key factors affecting the future microbiological water quality in rivers and tidal estuaries. A coupled 3D hydrodynamic and fecal coliform transport model was developed and applied to the Danshuei River estuarine system for predicting the influences of climate change on microbiological water quality. The hydrodynamic and fecal coliform model was validated using observational salinity and fecal coliform distributions. According to the analyses of the statistical error, predictions of the salinity and the fecal coliform concentration from the model simulation quantitatively agreed with the observed data. The validated model was then applied to predict the fecal coliform contamination as a result of climate change, including the change of freshwater discharge and the sea level rise. We found that the reduction of freshwater discharge under climate change scenarios resulted in an increase in the fecal coliform concentration. The sea level rise would decrease fecal coliform distributions because both the water level and the water volume increased. A reduction in freshwater discharge has a negative impact on the fecal coliform concentration, whereas a rising sea level has a positive influence on the fecal coliform contamination. An appropriate strategy for the effective microbiological management in tidal estuaries is required to reveal the persistent trends of climate in the future. PMID- 26545373 TI - The occurrence and removal of selected fluoroquinolones in urban drinking water treatment plants. AB - Fluoroquinolones (FQs) are a widely prescribed group of antibiotics. They enter the aqueous environment, where they are frequently detected, and can lead to a threat to human health. Drinking water treatment plants (DWTPs) play a key role in removing FQs from potable water. This study investigated the occurrence and removal of four selected FQs (norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL)) in three urban DWTPs in China. The treatment efficacy for each system was simultaneously evaluated. Two of the examined DWTPs used conventional treatment processes. The third used conventional processes followed by additional treatment processes (ozonation-biologically activated carbon (ozonation-BAC) and membrane technology). The average concentrations of the four FQs in the source water and the finished water ranged from 51 to 248 ng/L and from <5 to 46 ng/L, respectively. Based on residual concentrations, the conventional treatment system had a low removal of FQs. In contrast, the addition of advanced treatment processes such as the ozonation-BAC and membranes, substantially improved the removal of FQs. The finding of this study has important implications: even though coagulation-sedimentation and chlorination treatment processes can remove most target FQs, the typical practice of advanced treatment processes is necessary for the further removal. PMID- 26545374 TI - Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment. AB - BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare cancer arising from mesothelial cells lining the peritoneal surface. Little is known about the tumor microenvironment in regulating MPM oncogenesis. The current study defined the chemokine/cytokine expression profile and inflammatory responses within the MPM microenvironment. METHODS: Levels of 10 cytokines (Fractalkine, IFNgamma, IL-6, IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta, TNFalpha, VEGF) in matched ascites and sera from 15 MPM patients were measured using Milliplex immunoassays. Sera from six normal control sera were included. Statistical analyses included the Wilcoxon signed-rank test, the Mann-Whitney U test, bivariate analysis, and the R (2) coefficient of correlation. RESULTS: The median levels of IL-6 (3190 vs 3.18 ng/ml; p < 0.001), IL-8 (118 vs 4.93 ng/ml; p < 0.001), IP-10 (3923 vs 384 ng/ml; p < 0.001), and MCP-1 (2886 vs 544 ng/ml; p = 0.005) were significantly higher in the MPM ascites than in the matched MPM serum. In the MPM serum samples, the levels of IL-8 (4.93 vs 1.52 ng/ml; p = 0.002), MIP-1beta (53.8 vs 22.3; p = 0.016), TNFalpha (9.97 vs 4.5 ng/ml; p = 0.013), and VEGF (277 vs 105.4 ng/ml; p = 0.036) were significantly higher than in the control sera. CONCLUSION: The chemokines/cytokines in the MPM tumor microenvironment are distinct from those associated with inflammatory responses to infection or injury (e.g., IL-1, IL-2, TNFalpha, IFNgamma). These local changes reflect active reciprocal communication between tumor and associated stroma, which the authors predict is integral to MPM oncogenesis. Future studies will test this hypothesis and identify potential serum biomarkers for MPM. PMID- 26545375 TI - Cytoreductive Surgery and HIPEC as a Treatment Option for Laparoscopic Resection of Uterine Leiomyosarcoma with Morcellation: Early Results. AB - BACKGROUND: A new and frequently utilized treatment option for symptomatic uterine leiomyoma is laparoscopic resection with morcellation so the specimen can be extracted through a small abdominal incision or through the vagina. Some of these tumors (approximately 0.2 %) have malignant foci of uterine leiomyosarcoma (ULMS) that is widely disseminated in the process of resection. These patients are in need of effective additional treatments. METHODS: Patients with ULMS were treated with a standardized cytoreductive surgery (CRS), hyperthermic perioperative chemotherapy (HIPEC), and early postoperative intraperitoneal chemotherapy (EPIC) specifically designed for sarcomatosis. Distribution of disease by Peritoneal Cancer Index was recorded by preoperative computed tomography or magnetic resonance imaging and at the time of CRS. Completeness of cytoreduction score was determined after completion of CRS. Morbidity and mortality, as well as interval to start systemic chemotherapy, were prospectively recorded. RESULTS: Six patients with disseminated ULMS after morcellation or slicing underwent CRS and HIPEC plus EPIC. All six patients had complete visible clearing of sarcoma prior to perioperative chemotherapy. Early intervention after morcellation was associated with a lesser extent of disease. No serious morbidity or mortality was observed in early referral patients, and patients eligible for systemic chemotherapy were treated with perioperative chemotherapy within 6 weeks of the CRS. CONCLUSIONS: The future use of laparoscopic resection of ULMS with morcellation is currently under debate. However, patients after laparoscopic resection and morcellation have CRS and HIPEC plus EPIC as a treatment option. Results regarding short-term benefit are suggested by these early data, especially with early referral. PMID- 26545376 TI - Change of Patient-Reported Aesthetic Outcome Over Time and Identification of Factors Characterizing Poor Aesthetic Outcome After Breast-Conserving Therapy: Long-Term Results of a Prospective Cohort Study. AB - BACKGROUND: We analyzed the change of aesthetic outcome (AO) over time and explored factors characterizing poor AO after breast-conserving surgery (BCS). METHODS: This prospective single-center cohort study included 849 patients preoperatively planned for BCS between September 2007 and December 2011. Long term follow-up was made once in 2013. AO was measured by the Aesthetic Status (AS) of the Breast Cancer Treatment Outcome Scale questionnaire. Clinical, surgical, and pathologic variables were evaluated to identify predictors of poor AO. We applied single factor variance analyses and univariable logistic regression analyses for outcome analysis. RESULTS: The long-term follow-up rate in 2013 was 73 % (621 nonrecurrent with final BCS). A poor or fair AO was reported in 30 (4.8 %) and 98 (15.8 %) of these 621 patients, respectively. Single factor variance analysis showed a negative impact of higher specimen weight on AO (p < 0.001). Univariable logistic regression analysis revealed the following risk factors for poor AO: radial breast incision [odds ratio (OR) 1.97], periareolar incision (OR 1.85), fishmouth-shaped incision with resection of the nipple-areola complex (OR 8.12), impaired wound healing (OR 3.14), and seroma (OR 2.16). No patient rating her AO as fair or poor shortly after BCS improved in the long-term follow-up. CONCLUSIONS: The incidence of poor AO is relatively rare but increases in the long-term follow-up. Patients experiencing poor AO after BCS are likely to remain unsatisfied with the outcome over time. Factors predicting unfavorable AO can assist preoperative planning with regards to the choice between simple breast conserving techniques or more complex oncoplastic procedures. PMID- 26545377 TI - Novel and recurrent AID mutations underlie prevalent autosomal recessive form of HIGM in consanguineous patients. AB - Immunoglobulin class switch recombination deficiencies (Ig-CSR-D) are characterized by normal or elevated serum IgM level and absence of IgG, IgA, and IgE. Most reported cases are due to X-linked CD40L deficiency. Activation-induced cytidine deaminase deficiency is the most frequent autosomal recessive form, whereas CD40 deficiency is more rare. Herein, we present the first North African study on hyper IgM (HIGM) syndrome including 16 Tunisian patients. Phenotypic and genetic studies allowed us to determine their molecular basis. Three CD40LG mutations have been identified including two novels (c.348_351dup and c.782_*2del) and one already reported mutation (g.6182G>A). No mutation has been found in another patient despite the lack of CD40L expression. Interestingly, three AICDA mutations have been identified in 11 patients. Two mutations were novel (c.91T>C and c.389A>C found in one and five patients respectively), and one previously reported splicing mutation (c.156+1T>G) was found in five patients. Only one CD40-deficient patient, bearing a novel mutation (c.109T>G), has been identified. Thus, unlike previous reports, AID deficiency is the most frequent underlying molecular basis (68%) of Ig-CSR-D in Tunisian patients. This finding and the presence of specific recurrent mutations are probably due to the critical role played by inbreeding in North African populations. PMID- 26545379 TI - Branemark's legacy. PMID- 26545378 TI - Functional outcomes after supracricoid laryngectomy: what do we not know and what do we need to know? AB - Supracricoid laryngectomies (SCLs) are conservative organ-sparing surgical techniques for the treatment of selected T2-T4 laryngeal carcinomas. Although these procedures allow preserving the larynx and its functions, in several countries SCLs are not adopted in oncological protocols. One of the possible reasons to account for this choice is the complexity of post-surgical in-hospital management and the variability in functional results. The aim of this review is to analyse the literature on functional results after SCLs as knowledge on functional results will help in focusing on what is needed in the future to reach more standardized post-surgical procedures and homogeneous outcomes. The analysis of the length of hospital stay, feeding-tube removal time and time to eventual tracheotomy decannulation showed a marked variability across authors and centres. Several factors may come into play, including health-system organizations in different countries. In most studies in-depth description of the criteria applied for discharge, tracheotomy tube removal and commencement of oral feeding were not reported. Moreover, the review on swallowing functional outcomes showed marked variability, as well as a lack of consensus on how to assess swallowing after SCLs. The analysis of voice functional outcomes also revealed a marked variability; surprisingly, the tools applied in the assessments were very often not adequate for substitution voice. Literature review showed that voice- and swallowing-related quality of life are often satisfactory but the variability among centres is still too large. Therefore, there is a need for clearer clinical recommendations on early post-surgical management, tracheal-cannula and feeding tube removal criteria, voice- and swallowing-assessment protocol, rehabilitation need and timing. PMID- 26545380 TI - Numerical simulation of humidification and heating during inspiration in nose models with three different located septal perforations. AB - Nasal septum perforations (SP) are characterized by nasal obstruction, bleeding and crusting. The disturbed heating and humidification of the inhaled air are important factors, which cause these symptoms due to a disturbed airflow. Numerical simulations offer a great potential to avoid these limitations and to provide valid data. The aim of the study was to simulate the humidification and heating of the inhaled air in digital nose models with three different SPs and without SP. Four realistic bilateral nose models based on a multi-slice CT scan were created. The SP were located anterior caudal, anterior cranial and posterior caudal. One model was without SP. A numerical simulation was performed. Boundary conditions were based on previous in vivo measurements. Heating and humidification of the inhaled air were displayed, analyzed in each model and compared to each other. Anterior caudal SPs cause a disturbed decrease of temperature and humidity of the inhaled air. The reduced temperature and humidity values can still be shown in the posterior nose. The anterior cranial and the posterior caudal perforation have only a minor influence on heating and humidification. A reduced humidification and heating of the air can be shown by numerical simulations due to SP depending on their localization. The anterior caudal SP representing a typical localization after previous surgery has the biggest influence on heating and humidification. The results explain the typical symptoms such as crusting by drying-out the nasal mucosa. The size and the localization of the SP are essential for the symptoms. PMID- 26545381 TI - Concomitant corticosteroid nasal spray plus antihistamine (oral or local spray) for the symptomatic management of allergic rhinitis. AB - The purpose of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the symptomatic management of corticosteroid nasal spray plus antihistamine (oral or local spray) with that of either therapy given alone, or placebo in patients with allergic rhinitis (AR). The PRISMA guidelines for meta-analysis reporting were followed. Total nasal symptom scores and individual nasal symptom scores were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences (WMD) between treatments. A total of ten studies fulfilled eligibility. Three trials studied the combination therapy of corticosteroid nasal spray and oral antihistamine. Pooled results of two trials failed to show significant difference on total nasal symptoms between combination therapy and intranasal corticosteroid alone (WMD = -0.20, 95 % CI -0.38 to -0.01, P = 0.04). The qualitative analysis showed that combination therapy has greater efficacy than oral antihistamines alone or placebo in improving symptoms. Seven trials investigated corticosteroid nasal spray plus antihistamine nasal spray. The cumulative meta-analysis of six RCTs revealed that combination therapy was superior to solo intranasal corticosteroid (WMD = -1.16, 95 % CI -1.49 to -0.83, P < 0.00001), solo intranasal antihistamine (WMD = -1.73, 95 % CI -2.08 to -1.38, P < 0.00001), and placebo (WMD = -2.81, 95 % CI -3.16 to -2.47, P < 0.00001) in improving total nasal symptom scores. Intranasal corticosteroid plus oral antihistamine have similar efficacy to intranasal corticosteroid alone, greater efficacy than oral antihistamines alone or placebo in reducing nasal symptoms for AR patients. Intranasal corticosteroid plus intranasal antihistamine are significantly superior to either therapy given alone, or placebo. PMID- 26545382 TI - Clinical and Molecular Diagnostic Evaluation of Systemic Mastocytosis in the South-Eastern Hungarian Population Between 2001-2013--A Single Centre Experience. AB - Systemic mastocytosis (SM) is a rare chronic myeloproliferative neoplasm with only limited epidemiologic data published so far. We aimed to analyze the clinical and molecular diagnostic features, and the prognosis and cumulative incidence of SM cases in a cohort of south-eastern Hungarian patients of 13 year follow up. In the period 2001-2013, 35 consecutive SM cases were diagnosed in our regional centre. Immunophenotype, KIT D816V mutation frequency and clinical characteristics, and the prognosis impact of clinical subtypes were tested and compared with published data. Indolent SM (ISM) was diagnosed in 14 patients, SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 15 patients and aggressive SM (ASM) in 6 patients. The KIT D816V mutation was found in 11/14 (78%) of the ISM cases, in 12/15 (80%) of the SM-AHNMD cases and in 5/6 (83%) of the ASM cases. The life expectancy of ISM patients was better, whereas the SM-AHNMD and ASM groups exhibited a reduced median survival. The cumulative incidence for 13 year of the SM was 0.27/10,000. We detected lower 13 year cumulative SM incidence than of published epidemiologic data due to in our analyses involved only those patients who had bone marrow biopsy and histopathologically confirmed SM. This clinical overview clearly showed that the clinical characteristics differ between ISM (UP, anaphylaxis and osteoporosis) and SM-AHNMD/ASM (cytopenia, eosinophilia and splenomegaly). PMID- 26545383 TI - L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells. AB - Non-Hodgkin Lymphoma (NHL) constitutes a very heterogeneous group of diseases with different aggressiveness. Diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) are two clinically aggressive lymphomas from the germinal center, very heterogeneous and with different genetic signatures. Several intracellular pathways are involved in lymphomagenesis, being BCR/PI3K/AKT/mTOR and RAS/RAF pathways the most frequently ones. In this context the therapeutic potential of a mTOR inhibitor--everolimus--and a RAS/RAF pathway inhibitor- L744,832--was evaluated in two NHL cell lines. Farage and Raji cells were cultured in the absence and presence of several concentrations of everolimus and L744,832 in monotherapy and in combination with each other, as well as in association with the conventional chemotherapy drug vincristine. Our results show that everolimus and L744,832 induce antiproliferative and cytotoxic effect in a time-, dose-, and cell line-dependent manner, inducing cell death mainly by apoptosis. A potentiation effect was observed when the drugs were used in combination. In conclusion, the results suggest that everolimus and L744,832, alone or in combination, could provide therapeutic benefits in these subtypes of NHL. PMID- 26545384 TI - Colorectal surgery in a rural setting. AB - Colorectal surgery is increasingly being concentrated in high-volume tertiary centers, whereas it has been demonstrated that it can be performed safely and effectively even in low-volume hospitals. We analyzed data of patients who underwent major colorectal surgery in 1 year in a "rural" hospital, located on a small island, where a dynamic colorectal multidisciplinary team (MDT) and an enhanced recovery programme have been implemented. Primary endpoints were rate of laparoscopic resections, morbidity, mortality and number of lymph nodes retrieved and examined. Secondary endpoints were rate of R0 resections and length of postoperative stay. Seventy-six patients had surgery for a severe colorectal condition. Fifty-five resections have been performed, 38 by laparoscopy (69.1 %). Conversion rate was 5 %. Morbidity for resections was 21.8 %. General leak rate was 1.8 %, no leaks in laparoscopic resections. There was no difference in morbidity between open and laparoscopic resections. Postoperative stay was significantly shorter in laparoscopic vs open operations and in elective vs emergency operations. Number of lymph nodes retrieved was higher in laparoscopic vs open resections, 85.4 % of patients had 12 or more lymph nodes examined. Overall rate of R0 resections was 80.5 %, higher in laparoscopic vs open resections. Major colorectal surgery can be performed safely and effectively also in low-volume hospitals in the presence of a trained high-volume surgeon, an effective MDT and an Enhanced Recovery Programme. PMID- 26545385 TI - Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA. AB - Toll-like receptor (TLR) 13 and TLR2 are the major sensors of Gram-positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA-derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A-treated Staphylococcus aureus activate human peripheral blood mononuclear cells (PBMCs) only via TLR2, implying single-stranded (ss) RNA as major stimulant. Here, we identify human TLR8 as functional TLR13 equivalent that promiscuously senses ssRNA. Accordingly, Sa19 and mitochondrial (mt) 16S rRNA sequence-derived oligoribonucleotides (ORNs) stimulate PBMCs in a MyD88-dependent manner. These ORNs, as well as S. aureus-, Escherichia coli-, and mt-RNA, also activate differentiated human monocytoid THP 1 cells, provided they express TLR8. Moreover, Unc93b1(-/-)- and Tlr8(-/-)-THP-1 cells are refractory, while endogenous and ectopically expressed TLR8 confers responsiveness in a UR/URR RNA ligand consensus motif-dependent manner. If TLR8 function is inhibited by suppression of lysosomal function, antibiotic treatment efficiently blocks bacteria-driven inflammatory responses in infected human whole blood cultures. Sepsis therapy might thus benefit from interfering with TLR8 function. PMID- 26545387 TI - Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion. PMID- 26545386 TI - Health-related quality of life after first-line anti-cancer treatments for advanced non-small cell lung cancer in clinical practice. AB - PURPOSE: This study attempted to compare changes in the Quality-of-Life (QoL) scores after three different first-line anti-cancer treatments for advanced non small cell lung cancer (NSCLC) in a real-world clinical setting. PATIENTS AND METHODS: From May 2011 to December 2013, we prospectively measured the QoL scores of patients with locally advanced or metastatic NSCLC using the World Health Organization Quality-of-Life-Brief (WHOQOL-BREF) questionnaire. Each QoL measurement was matched by age and sex with one healthy referent from the National Health Interview Survey. Dynamic changes in patients' QoL scores and major determinants were repeatedly assessed by construction of a mixed-effects model to adjust for possible confounders. RESULTS: A total of 336 patients with 577 QoL measurements related to first-line anti-cancer treatments were enrolled. Performance status was the most important predictor of QoL scores in all domains after controlling for potential confounders. With age- and sex-matched healthy subjects as the reference, patients treated with gemcitabine + platinum showed significantly lower scores in multiple physical and psychological domain items in the WHOQOL-BREF. However, pemetrexed + platinum and gefitinib/erlotinib affected patients' QoL scores in 'energy/fatigue' and 'daily activities' with smaller magnitudes, and the scores appeared to improve after 3-4 months of treatment. CONCLUSIONS: Patients receiving gemcitabine + platinum as first-line anti-cancer treatment for advanced NSCLC experienced relatively poor QoL scores throughout treatment course. Studies to develop a real-time computerized system automatically updating the mixed-effects model for QoL to facilitate participatory clinical decision making by physicians, patients, and their families merit further research. PMID- 26545388 TI - How to assess quality in primary care. PMID- 26545389 TI - The Role of Piezoelectric Instrumentation in Rhinoplasty Surgery. AB - BACKGROUND: In rhinoplasty surgery, management of the bony vault and lateral walls is most often performed with mechanical instruments: saws, chisels, osteotomes, and rasps. Over the years, these instruments have been refined to minimize damage to the surrounding soft tissues and to maximize precision. OBJECTIVES: This article will present the evolution of the authors' current operative technique based on 185 clinical cases performed over an 19-month period using piezoelectric instrumentation (PEI). METHODS: A two-part study of cadaver dissections and clinical cases was performed using PEI. Evolution of the authors' clinical technique and the operative sequence were recorded. RESULTS: Thirty cadaver dissections and 185 clinical cases were performed using PEI, including 82 primary and 103 secondary cases. An extended subperiosteal dissection was developed to visualize all aspects of the open rhinoplasty including the osteotomies. Ultrasonic rhinosculpture (URS) was utilized in 95 patients to shape the bony vault without osteotomies. To date, 11 revisions (6%) have been performed. There were no cases of bone asymmetry, irregularity, or excessive narrowing requiring a revision. CONCLUSIONS: Based on the authors' experience, adoption of PEI is justified and offers more precise analysis and surgical execution with superior results in altering the osseocartilaginous vault. With extensive exposure, surgeons can make an accurate diagnosis of bony deformity and safely contour the bones to achieve narrowing and symmetry of the bony dorsum. Stable osteotomies can be performed under direct vision with precise mobilization and control. As a result of PEI, the upper third of the rhinoplasty operation is no longer shrouded in mystery. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26545390 TI - Effect of a Hospital-wide High-Flow Nasal Cannula Protocol on Clinical Outcomes and Resource Utilization of Bronchiolitis Patients Admitted to the PICU. AB - OBJECTIVE: To assess the association of the introduction of a high-flow nasal cannula (HFNC) protocol with clinical outcomes and hospital charges of infants with bronchiolitis initially admitted to the PICU. METHODS: We conducted a retrospective, nonrandomized, preintervention-postintervention study of infants with bronchiolitis initially admitted to the PICU for HFNC. We compared patients admitted in the 24 months before and after protocol initiation for HFNC use on the general wards. The primary outcome assessed was length of hospital stay (LOS), and the secondary outcomes included total hospital charges, intubation, and 30-day readmission. We conducted bivariate analysis using chi2 test for categorical variables and Student's t test or Wilcoxon rank sum test for continuous variables. RESULTS: Two hundred and ninety patients were admitted to the PICU on HFNC; 120 patients were admitted before and 170 admitted after the introduction of HFNC use on the general wards. Comparing the 2 groups, the median LOS was significantly reduced (4 days vs 3 days; P < .001), as was the median total hospital charges ($12 257 vs $9337; P < .001). After starting HFNC use on the wards, 30% of patients initially admitted to the PICU were ultimately transferred to the wards while still on HFNC. There was no difference in intubation rate or 30-day readmission between the 2 groups. CONCLUSIONS: For bronchiolitis patients initially admitted to the PICU, initiating a guideline for HFNC use on the general pediatric wards is associated with reduced total hospital LOS and total hospital charges, with no difference in intubation rates or 30-day readmission. PMID- 26545391 TI - Justify Your Vice. PMID- 26545392 TI - Randomized comparison trial of gait training with and without compelled weight shift therapy in individuals with chronic stroke. AB - OBJECTIVE: To compare the effects of gait training combined with compelled weight shift therapy and gait training alone on velocity and gait symmetry in patients with chronic stroke. DESIGN: Single-blind randomized controlled trial. PARTICIPANTS: Patients ( N=28) with chronic stroke and stance asymmetry toward the non-paretic side. INTERVENTIONS: Six weeks of gait training combined with compelled weight-shift therapy via a shoe lift applied under the non-paretic leg (experimental group, n=14) or gait training alone (control group, n=14). MAIN MEASURES: Percentage of total body weight carried by the paretic limb, gait velocity and gait spatiotemporal symmetry ratios including step symmetry, stance symmetry, swing symmetry and overall temporal symmetry. RESULTS: When comparing the two groups, weight bearing on the affected side increased more significantly in experimental group than in control group (40.14+/-3.77, 38.28+/-4.06) after the end of treatment and also after a three-month follow-up (44.42+/-3.5, 38.5+/ 3.77) (P<0.05). Among the experimental and control groups, there were no significant differences of gait velocity (cm/s) after six weeks of treatment (49.82+/-16.82, 42.66+/-18.75) and also after a three-month follow-up (50.94+/ 16.27, 41.66+/-17.58) ( P>0.05). There were no significant differences of gait spatiotemporal symmetry ratios including step symmetry, stance symmetry, swing symmetry and overall temporal symmetry between the two groups after six weeks of treatment and also at three-month follow-up ( P>0.05). CONCLUSIONS: This study did not confirm that the effect of gait training combined with compelled body weight shift therapy was better than gait training alone on improving velocity and gait symmetry in patients with chronic stroke. PMID- 26545393 TI - Comment on: A critical analysis of the internal logic in the Life-Space Assessment (LSA) composite score and suggested solutions. PMID- 26545394 TI - "You Better Say Your Prayers and Get Ready": Guns Within the Context of Partner Abuse. AB - The present study used focus groups to collect qualitative data to better understand the complexity of how women with domestic violence experiences feel about gun violence and protections from gun violence within the context of partner violence. Participants consisted of 42 women who were recruited through domestic violence shelters and programs in a single U.S. state. Three main themes were examined in the focus group discussions: (a) guns used within the context of partner abuse, (b) victims using guns as protection from an abuser, and (c) mandated gun restrictions as protection in partner abuse. A total of nine subthemes were organized under the three general themes. Within the first main theme, participants discussed that although abuse occurs with and without guns, guns are uniquely dangerous. In the second main theme, participants expressed concern regarding the dangers of using a gun for self-defense as well as the individual right to own a gun for self-defense. In the third main theme, participants expressed their frustrations that victims are not taken seriously by the justice system and the difficulties of enforcing mandated gun restrictions. The findings have implications for developing protective strategies against gun violence for victims of partner violence. PMID- 26545395 TI - The Potential for Screening for Intimate Partner Violence in Community Pharmacies: An Exploratory Study of Female Consumers' Perspectives. AB - Intimate partner violence (IPV) is a substantial public health problem. The U.S. Preventive Services Task Force recently updated guidelines to recommend IPV screening for all women of childbearing age. Expansion of screening efforts to the community pharmacy setting could provide an opportunity to substantially impact the health of consumers. To date, no research has explored consumers' perspective on IPV screening in the community pharmacy environment. To address this gap, a descriptive survey research study was conducted to examine female consumers' attitudes and preferences for IPV screening in community pharmacies. Female pharmacy customers ( N = 60) completed an online survey assessing knowledge of and attitudes about community pharmacies as sources of health care advice, beliefs about IPV and IPV screening, and perspectives on IPV screening in the community pharmacy environment. Consumers who utilized pharmacies with more patient care services were more likely to report interest in IPV screening in the pharmacy environment. The majority of respondents thought IPV screening is an important thing to do (85.0%), and 33.3% agreed that it should happen in a pharmacy. A statistically significant relationship between the belief that the pharmacy is a good place for health education and preference for IPV screening in the community pharmacy environment was found, r(58) = .43, p < .001. Concern regarding the time required to conduct screenings and about the availability of appropriate space were identified as potential barriers to screening in the pharmacy environment. PMID- 26545396 TI - The Situational Context of Adolescent Homicide Victimization in Johannesburg, South Africa. AB - Although studies have described the incidence and epidemiology of adolescent homicide victimization in South Africa, little is known about the situational contexts in which they occur. This study aimed to describe the victim, offender, and event characteristics of adolescent homicide and to generate a typology based on the particular types of situational contexts associated with adolescent homicide in South Africa. Data on homicides among adolescents (15-19 years) that occurred in Johannesburg (South Africa) during the period 2001-2007 were obtained from the National Injury Mortality Surveillance System (NIMSS) and police case records. Of the 195 cases available for analysis, 81% of the victims were male. Most of the offenders were male (90%), comprising of strangers (42%) and friends/acquaintances (37%). Arguments (33%) were the most common precipitating circumstances, followed by revenge (11%), robbery (11%), and acts of vigilantism/retribution for a crime (8%). Through the use of cluster analysis, the study identified three categories of adolescent homicide: (a) male victims killed by strangers during a crime-related event, (b) male victims killed by a friend/acquaintance during an argument, and (c) female victims killed by male offenders. The results can serve to inform the development of tailored and focused strategies for the prevention of adolescent homicide. PMID- 26545397 TI - PRIDE Inspector Toolsuite: Moving Toward a Universal Visualization Tool for Proteomics Data Standard Formats and Quality Assessment of ProteomeXchange Datasets. AB - The original PRIDE Inspector tool was developed as an open source standalone tool to enable the visualization and validation of mass-spectrometry (MS)-based proteomics data before data submission or already publicly available in the Proteomics Identifications (PRIDE) database. The initial implementation of the tool focused on visualizing PRIDE data by supporting the PRIDE XML format and a direct access to private (password protected) and public experiments in PRIDE.The ProteomeXchange (PX) Consortium has been set up to enable a better integration of existing public proteomics repositories, maximizing its benefit to the scientific community through the implementation of standard submission and dissemination pipelines. Within the Consortium, PRIDE is focused on supporting submissions of tandem MS data. The increasing use and popularity of the new Proteomics Standards Initiative (PSI) data standards such as mzIdentML and mzTab, and the diversity of workflows supported by the PX resources, prompted us to design and implement a new suite of algorithms and libraries that would build upon the success of the original PRIDE Inspector and would enable users to visualize and validate PX "complete" submissions. The PRIDE Inspector Toolsuite supports the handling and visualization of different experimental output files, ranging from spectra (mzML, mzXML, and the most popular peak lists formats) and peptide and protein identification results (mzIdentML, PRIDE XML, mzTab) to quantification data (mzTab, PRIDE XML), using a modular and extensible set of open-source, cross platform libraries. We believe that the PRIDE Inspector Toolsuite represents a milestone in the visualization and quality assessment of proteomics data. It is freely available at http://github.com/PRIDE-Toolsuite/. PMID- 26545398 TI - Integration of Metabolomics and Transcriptomics Reveals Major Metabolic Pathways and Potential Biomarker Involved in Prostate Cancer. AB - Prostate cancer is a highly prevalent tumor affecting millions of men worldwide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/ml). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia. PMID- 26545399 TI - Novel N-terminal and Lysine Methyltransferases That Target Translation Elongation Factor 1A in Yeast and Human. AB - Eukaryotic elongation factor 1A (eEF1A) is an essential, highly methylated protein that facilitates translational elongation by delivering aminoacyl-tRNAs to ribosomes. Here, we report a new eukaryotic protein N-terminal methyltransferase, Saccharomyces cerevisiae YLR285W, which methylates eEF1A at a previously undescribed high-stoichiometry N-terminal site and the adjacent lysine. Deletion of YLR285W resulted in the loss of N-terminal and lysine methylation in vivo, whereas overexpression of YLR285W resulted in an increase of methylation at these sites. This was confirmed by in vitro methylation of eEF1A by recombinant YLR285W. Accordingly, we name YLR285W as elongation factor methyltransferase 7 (Efm7). This enzyme is a new type of eukaryotic N-terminal methyltransferase as, unlike the three other known eukaryotic N-terminal methyltransferases, its substrate does not have an N-terminal [A/P/S]-P-K motif. We show that the N-terminal methylation of eEF1A is also present in human; this conservation over a large evolutionary distance suggests it to be of functional importance. This study also reports that the trimethylation of Lys(79) in eEF1A is conserved from yeast to human. The methyltransferase responsible for Lys(79) methylation of human eEF1A is shown to be N6AMT2, previously documented as a putative N(6)-adenine-specific DNA methyltransferase. It is the direct ortholog of the recently described yeast Efm5, and we show that Efm5 and N6AMT2 can methylate eEF1A from either species in vitro. We therefore rename N6AMT2 as eEF1A KMT1. Including the present work, yeast eEF1A is now documented to be methylated by five different methyltransferases, making it one of the few eukaryotic proteins to be extensively methylated by independent enzymes. This implies more extensive regulation of eEF1A by this posttranslational modification than previously appreciated. PMID- 26545402 TI - Partnership Status and Socioeconomic Factors in Relation to Health Behavior Changes after a Diagnosis of Ductal Carcinoma In Situ. AB - BACKGROUND: Change in health behaviors can occur among women newly diagnosed with ductal carcinoma in situ (DCIS). We sought to understand whether partnership status and socioeconomic status (SES) affected behavioral changes in body weight, physical activity, alcohol consumption, and smoking. METHODS: The Wisconsin In Situ Cohort (WISC) study comprises 1,382 women diagnosed with DCIS with information on demographics, SES factors, and pre- and post-DCIS diagnosis health related behaviors. Logistic regression models were used to determine the association between partnership status, education, and income with change in behavior variables. RESULTS: Higher educational attainment was associated with lower likelihood of stopping physical activity [OR, 0.45; 95% confidence interval (CI), 0.32-0.63; college vs. high school degree], or starting to drink alcohol (OR, 0.34; 95% CI, 0.15-0.80). Results suggested that higher family income was associated with lower likelihood of gaining >5% body mass index (P = 0.07) or stopping physical activity (P = 0.09). Living with a partner was not strongly associated with behavior changes. CONCLUSION: Higher educational attainment and higher income, but not living with a partner, were associated with positive health behaviors after a DCIS diagnosis. IMPACT: The associations between higher educational attainment and, to a lesser extent, higher income with positive health behaviors underscore the importance of considering SES when identifying those at risk for negative behavioral change after DCIS diagnosis. PMID- 26545400 TI - Life Stage-specific Proteomes of Legionella pneumophila Reveal a Highly Differential Abundance of Virulence-associated Dot/Icm effectors. AB - Major differences in the transcriptional program underlying the phenotypic switch between exponential and post-exponential growth of Legionella pneumophila were formerly described characterizing important alterations in infection capacity. Additionally, a third state is known where the bacteria transform in a viable but nonculturable state under stress, such as starvation. We here describe phase related proteomic changes in exponential phase (E), postexponential phase (PE) bacteria, and unculturable microcosms (UNC) containing viable but nonculturable state cells, and identify phase-specific proteins. We present data on different bacterial subproteomes of E and PE, such as soluble whole cell proteins, outer membrane-associated proteins, and extracellular proteins. In total, 1368 different proteins were identified, 922 were quantified and 397 showed differential abundance in E/PE. The quantified subproteomes of soluble whole cell proteins, outer membrane-associated proteins, and extracellular proteins; 841, 55, and 77 proteins, respectively, were visualized in Voronoi treemaps. 95 proteins were quantified exclusively in E, such as cell division proteins MreC, FtsN, FtsA, and ZipA; 33 exclusively in PE, such as motility-related proteins of flagellum biogenesis FlgE, FlgK, and FliA; and 9 exclusively in unculturable microcosms soluble whole cell proteins, such as hypothetical, as well as transport/binding-, and metabolism-related proteins. A high frequency of differentially abundant or phase-exclusive proteins was observed among the 91 quantified effectors of the major virulence-associated protein secretion system Dot/Icm (> 60%). 24 were E-exclusive, such as LepA/B, YlfA, MavG, Lpg2271, and 13 were PE-exclusive, such as RalF, VipD, Lem10. The growth phase-related specific abundance of a subset of Dot/Icm virulence effectors was confirmed by means of Western blotting. We therefore conclude that many effectors are predominantly abundant at either E or PE which suggests their phase specific function. The distinct temporal or spatial presence of such proteins might have important implications for functional assignments in the future or for use as life-stage specific markers for pathogen analysis. PMID- 26545403 TI - A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry. AB - BACKGROUND: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, in several GWAS. Results outside this region have varied. METHODS: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. RESULTS: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 * 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 * 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 * 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 * 10(-8), P = 7.0 * 10(-7), and P = 8.4 * 10(-7), respectively; located in the CDKN2A/B gene region). CONCLUSIONS: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity. IMPACT: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. PMID- 26545401 TI - Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry. AB - Many species possess an endogenous circadian clock to synchronize internal physiology with an oscillating external environment. In plants, the circadian clock coordinates growth, metabolism and development over daily and seasonal time scales. Many proteins in the circadian network form oscillating complexes that temporally regulate myriad processes, including signal transduction, transcription, protein degradation and post-translational modification. In Arabidopsis thaliana, a tripartite complex composed of EARLY FLOWERING 4 (ELF4), EARLY FLOWERING 3 (ELF3), and LUX ARRHYTHMO (LUX), named the evening complex, modulates daily rhythms in gene expression and growth through transcriptional regulation. However, little is known about the physical interactions that connect the circadian system to other pathways. We used affinity purification and mass spectrometry (AP-MS) methods to identify proteins that associate with the evening complex in A. thaliana. New connections within the circadian network as well as to light signaling pathways were identified, including linkages between the evening complex, TIMING OF CAB EXPRESSION1 (TOC1), TIME FOR COFFEE (TIC), all phytochromes and TANDEM ZINC KNUCKLE/PLUS3 (TZP). Coupling genetic mutation with affinity purifications tested the roles of phytochrome B (phyB), EARLY FLOWERING 4, and EARLY FLOWERING 3 as nodes connecting the evening complex to clock and light signaling pathways. These experiments establish a hierarchical association between pathways and indicate direct and indirect interactions. Specifically, the results suggested that EARLY FLOWERING 3 and phytochrome B act as hubs connecting the clock and red light signaling pathways. Finally, we characterized a clade of associated nuclear kinases that regulate circadian rhythms, growth, and flowering in A. thaliana. Coupling mass spectrometry and genetics is a powerful method to rapidly and directly identify novel components and connections within and between complex signaling pathways. PMID- 26545404 TI - Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype. AB - BACKGROUND: Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis have received limited attention. METHODS: Study participants were 1,140 invasive breast cancer patients from phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer-specific and overall survival was assessed using Cox proportional hazards models. RESULTS: During follow-up (median = 13.5 years), 450 patients died, 61% due to breast cancer (n = 276). High parity (3+ births) and recent birth (<5 years before diagnosis) were positively associated with breast cancer-specific mortality, independent of age, race, and selected socioeconomic factors [parity, reference = nulliparous, adjusted HR = 1.76; 95% confidence interval (CI) = 1.13-2.73; birth recency, reference = 10+ years, adjusted HR = 1.29; 95% CI, 0.79-2.11]. The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. CONCLUSIONS: Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long term survivors. IMPACT: The biologic effects of parity and birth recency may extend from etiology to tumor promotion and progression. PMID- 26545405 TI - Body Mass Index at Diagnosis and Breast Cancer Survival Prognosis in Clinical Trial Populations from NRG Oncology/NSABP B-30, B-31, B-34, and B-38. AB - BACKGROUND: Body mass index (BMI) has been associated with breast cancer outcomes. However, few studies used clinical trial settings where treatments and outcomes are consistently evaluated and documented. There are also limited data assessing how patient/disease characteristics and treatment may alter the BMI breast cancer association. METHODS: We evaluated 15,538 breast cancer participants from four NSABP protocols. B-34 studied early-stage breast cancer patients (N = 3,311); B-30 and B-38 included node-positive breast cancer patients (N = 5,265 and 4,860); and B-31 studied node-positive and HER2-positive breast cancer patients (N = 2,102). We used Cox proportional hazards regression to calculate adjusted hazards ratios (HR) for risk of death and recurrence, and conducted separate analyses by estrogen receptor (ER) status and treatment group. RESULTS: In B-30, increased BMI was significantly related to survival. Compared with BMI < 25, HRs were 1.04 for BMI 25 to 29.9 and 1.18 for BMI >= 30 (P = 0.02). Separate analyses indicated the significant relationship was only in ER positive disease (P = 0.002) and the subgroup treated with doxorubicin/cyclophosphamide (P = 0.005). There were no significant trends across BMI for the other three trials. Similar results were found for recurrence. Increased BMI was significantly related to recurrence in B-30 (P = 0.03); and the significant relationship was only in ER-positive breast cancers (P = 0.001). Recurrence was also significant among ER-positive disease in B-38 (P = 0.03). CONCLUSIONS: In our investigation, we did not find a consistent relationship between BMI at diagnosis and breast cancer recurrence or death. IMPACT: This work demonstrates that the heterogeneity of breast cancer between different breast cancer populations and the different therapies used to treat them may modify any association that exists between BMI and breast cancer outcome. PMID- 26545408 TI - Synergistic Interaction within Bifunctional Ruthenium Nanoparticle/SILP Catalysts for the Selective Hydrodeoxygenation of Phenols. AB - Ruthenium nanoparticles immobilized on acid-functionalized supported ionic liquid phases (Ru NPs@SILPs) act as efficient bifunctional catalysts in the hydrodeoxygenation of phenolic substrates under batch and continuous flow conditions. A synergistic interaction between the metal sites and acid groups within the bifunctional catalyst leads to enhanced catalytic activities for the overall transformation as compared to the individual steps catalyzed by the separate catalytic functionalities. PMID- 26545407 TI - Longitudinal Change in Mammographic Density among ER-Positive Breast Cancer Patients Using Tamoxifen. AB - Tamoxifen-associated mammographic density (MD) reductions are linked to improved breast cancer survival. We evaluated MD at six time points to determine the timing of greatest reduction following tamoxifen initiation. We sampled 40 Kaiser Permanente Northwest estrogen receptor (ER)-positive breast cancer patients from a prior study of MD change, according to tamoxifen use duration and age at diagnosis: <4 years tamoxifen and <=50 years (N = 6) or >50 years (N = 10) old; >=4 years tamoxifen and <=50 years (N = 13) or >50 years (N = 11) old. A single reader evaluated percent MD in the contralateral breast on baseline (pre diagnosis) and five approximately yearly post-diagnostic (T1 to T5) mammograms. Mean MD change was calculated. Interactions with age (<=50 and >50 years), tamoxifen duration (<4 and >=4 years), and baseline MD (tertiles) were tested in linear regression models. Overall, the largest MD decline occurred by T1 (mean 4.5%) with little additional decline by T5. Declines differed by tertile of baseline MD (Pinteraction < 0.01). In the highest tertile, the largest reduction occurred by T1 (mean 14.9%), with an additional reduction of 3.6% by T5. Changes were smaller in the middle and lowest baseline MD tertiles, with cumulative reductions of 3.0% and 0.4% from baseline to T5, respectively. There were no differences by age (Pinteraction = 0.36) or tamoxifen duration (Pinteraction = 0.42). Among ER-positive patients treated with tamoxifen and surviving >=5 years, most of the MD reduction occurred within approximately 12 months of tamoxifen initiation, suggesting that MD measurement at a single time point following tamoxifen initiation can identify patients with substantial density declines. PMID- 26545406 TI - Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. AB - BACKGROUND: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines. The development of noninvasive and accurate BE detection assays could potentially identify many of these undiagnosed BE patients. METHODS: DNA methylation is a common epigenetic alteration in BE. Therefore, we conducted a genome-wide methylation screen to identify potential BE biomarkers. Samples from SQ (N = 12), stomach (N = 28), and BE (N = 29) were analyzed and methylation levels at over 485,000 CpG sites were compared. Pyrosequencing assays were used to validate the results and MethyLight assays were developed to detect the methylated alleles in endoscopic brushings. RESULTS: We discovered two genes, B3GAT2 and ZNF793, that are aberrantly methylated in BE. Clinical validation studies confirmed B3GAT2 and ZNF793 methylation levels were significantly higher in BE samples (median = 32.5% and 33.1%, respectively) than in control tissues (median = 2.29% and 2.52%, respectively; P < 0.0001 for both genes). Furthermore, gene-specific MethyLight assays could accurately detect BE (P < 0.0001 for both) in endoscopic brushing samples. CONCLUSION: B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples. IMPACT: These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE. PMID- 26545409 TI - A multi-method review of home-based chemotherapy. AB - This study summarises research- and practice-based evidence on home-based chemotherapy, and explores existing delivery models. A three-pronged investigation was conducted consisting of a literature review and synthesis of 54 papers, a review of seven home-based chemotherapy programmes spanning four countries, and two case studies within the Canadian province of Ontario. The results support the provision of home-based chemotherapy as a safe and patient centred alternative to hospital- and outpatient-based service. This paper consolidates information on home-based chemotherapy programmes including services and drugs offered, patient eligibility criteria, patient views and experiences, delivery structures and processes, and common challenges. Fourteen recommendations are also provided for improving the delivery of chemotherapy in patients' homes by prioritising patient-centredness, provider training and teamwork, safety and quality of care, and programme management. The results of this study can be used to inform the development of an evidence-informed model for the delivery of chemotherapy and related care, such as symptom management, in patients' homes. PMID- 26545410 TI - Pancreaticoduodenectomy with venous reconstruction using cold-stored vein allografts: long-term results of a single center experience. AB - BACKGROUND: The use of cadaveric vein allografts was first described by our group as a feasible option for venous reconstruction. The aim of this study was to report long-term results of this innovative technique. METHODS: Cold-stored veins harvested from donor cadavers were used as homologous grafts for venous reconstruction after vascular resection during pancreaticoduodenectomy. Surgical technique included patch closure or segmental interposition. Graft patency was assessed by computed tomography postoperatively and during follow-up. Postoperative morbidity and mortality were also analyzed. RESULTS: Eleven patients underwent venous resection and reconstruction by using fresh vein allografts for patch closure in four cases, conduit interposition in six cases and a Y-shaped graft interposition in one case. Median clamping time, operative time and estimated blood loss were 30 min, 6.6 h, and 337 ml, respectively. One patient, who had preoperative SMV thrombus, developed early portal vein thrombosis and died. Among the remaining 10 patients, there were no cases of graft thrombosis or stenosis during active follow-up (median 9, range 1-23, months). CONCLUSIONS: Our experience with cold-stored vein allografts suggests that this technique is a useful option for treating major vascular resections during pancreaticoduodenectomy with good results on follow-up. PMID- 26545411 TI - A bead-based assay in the work-up of suspected platelet alloimmunization. AB - BACKGROUND: Alloantibodies against human platelet antigens (HPAs) are of clinical significance in immune-mediated thrombocytopenia such as fetal/neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and platelet (PLT) transfusion refractoriness. The gold standard for the detection of these antibodies is the monoclonal antibody immobilization of PLT antigens (MAIPA) assay. Both requirement of typed donor PLT panels and technical expertise often restrict its use to reference laboratories. STUDY DESIGN AND METHODS: An easy-to use, bead-based assay (BBA) has been introduced recently. In this study, we compared MAIPA and BBA test results for 126 serum samples from women who gave birth to a child with FNAIT including rare HPA specificities (n = 111) and from patients with PLT transfusion refractoriness (n = 15). RESULTS: For sera with defined allospecificities, the number of BBA false-negatives was 12 of 126, or 9.5%, and the number of BBA false-positives (i.e., detection of additional specificities) was two of 126, or 1.6%. BBA had major problems in detecting antibodies against HPA-3a (3/15 undetected = 20% failure rate) and HPA-3b (5/6 undetected = 83.3% failure rate), but performed well in detecting typical FNAIT- or PLT transfusion refractoriness-associated antibodies including HPA-1a (35/35 = 100%), HPA-1b (15/15 = 100%), HPA-5b (22/24 = 91.6%), and glycoprotein IV (6/6 = 100%). CONCLUSION: BBA might be a useful and time-saving tool in the initial laboratory work-up of suspected PLT alloimmunization when an appropriate algorithm ensures follow-up investigation of BBA-negative sera. PMID- 26545412 TI - Asymmetric Bronsted Acid Catalyzed Synthesis of Triarylmethanes-Construction of Communesin and Spiroindoline Scaffolds. AB - Aza-ortho-quinone methides allow the straightforward asymmetric synthesis of natural-product-inspired indole scaffolds possessing a quaternary stereocenter. Our approach provides access to diverse communesin and spiroindoline derivatives with high enantioselectivity under mild reaction conditions. Predictable substitution patterns are found to be the key to our regiodivergent protocols. PMID- 26545414 TI - Short-lived climate pollutants: a focus for hot air. PMID- 26545413 TI - Diagnostic value of radiological imaging pre- and post-drainage of pleural effusions. AB - Patients with an unexplained pleural effusion often require urgent investigation. Clinical practice varies due to uncertainty as to whether an effusion should be drained completely before diagnostic imaging. We performed a retrospective study of patients undergoing medical thoracoscopy for an unexplained effusion. In 110 patients with paired (pre- and post-drainage) chest X-rays and 32 patients with paired computed tomography scans, post-drainage imaging did not provide additional information that would have influenced the clinical decision-making process. PMID- 26545415 TI - What next for the malaria RTS,S vaccine candidate? PMID- 26545416 TI - Canada's healthy future? PMID- 26545417 TI - Re-engaging the health community around peace. PMID- 26545418 TI - A Lancet Commission on obesity. PMID- 26545421 TI - Conflicts worsen global hunger crisis. PMID- 26545422 TI - The proper study of mankind. PMID- 26545427 TI - J Donald Millar. PMID- 26545428 TI - Alzheimergate: neither miscommunication nor sensationalism. PMID- 26545429 TI - Polio vaccination in Pakistan: by force or by volition? PMID- 26545430 TI - Faith-based organisations and health care: invest, don't proselytise. PMID- 26545431 TI - Could upright posture be harmful in the early stages of stroke? PMID- 26545432 TI - Could upright posture be harmful in the early stages of stroke? - Author's reply. PMID- 26545433 TI - RTS,S/AS01 malaria vaccine and child mortality. PMID- 26545434 TI - RTS,S/AS01 malaria vaccine and child mortality. PMID- 26545435 TI - Intracerebral haemorrhage, atrial fibrillation, and anticoagulation. PMID- 26545436 TI - Late-onset effects of radiation and chronic kidney disease. PMID- 26545437 TI - Intracerebral haemorrhage, atrial fibrillation, and anticoagulation - Authors' reply. PMID- 26545438 TI - Department of Error. PMID- 26545439 TI - Department of Error. PMID- 26545440 TI - The Nagasaki Atomic Bomb Survivors' Tumor Tissue Bank. PMID- 26545441 TI - An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis. AB - For patients with normal renal function, the recommended ceftaroline fosamil dose is a 600 mg 1-h intravenous (i.v.) infusion every 12 h (q12h). In patients with a creatinine clearance of <=30 mL/min, including those with end-stage renal disease (ESRD), the recommended dose is a 200 mg 1-h i.v. infusion q12h. This phase 1 study (NCT01664065) evaluated the pharmacokinetics, safety and tolerability of ceftaroline fosamil 200 mg 1-h i.v. infusion in patients with ESRD. Patients with ESRD (n=8) participated in two treatment periods (ceftaroline fosamil 200 mg administered pre- and post-haemodialysis) separated by >1 week. Healthy volunteers (n=7) received a single 600 mg dose of ceftaroline fosamil. Blood (pre and post-haemodialysis) and dialysate samples were obtained for pharmacokinetic analysis. In patients with ESRD, the geometric mean [coefficient of variation (%CV)] plasma ceftaroline area under the plasma concentration-time curve from zero to infinity (AUC0-infinity) following post-haemodialysis ceftaroline fosamil 200 mg infusion was 64.8 (38.9)MUg.h/mL, similar to that in volunteers following a 600 mg infusion [62.7 (9.4)MUg.h/mL]. Ceftaroline AUC0-infinity decreased by ca. 50% when infusion was initiated pre-haemodialysis. In the pre-haemodialysis treatment period, 80% of the ceftaroline fosamil dose was recovered in dialysate as ceftaroline (73%) and ceftaroline M-1 (7%). The frequency of adverse events was similar across patients with ESRD (pre- and post-haemodialysis) and volunteers (43%, 50% and 43% of subjects, respectively). Ceftaroline fosamil 200 mg 1-h i.v. infusion q12h, administered post-haemodialysis on dialysis days, is an appropriate dosage regimen for ESRD patients. PMID- 26545442 TI - Examining the feasibility and tolerability of a clinically informed multisite, repetitive transcranial magnetic stimulation protocol. AB - BACKGROUND: Multi-site repetitive transcranial magnetic stimulation (rTMS) has been applied experimentally in the treatment of obsessive compulsive disorder (OCD). NEW METHOD: This study was conducted to systematically evaluate the safety, tolerability and neurocognitive effects of rTMS applied to three cortical regions over a period of three months. NEW METHOD: Twenty healthy participants aged 22-33 years were randomly allocated to receive one session of active or sham stimulation of low and high frequency rTMS applied sequentially to the pre supplementary motor area, right-dorsolateral prefrontal cortex and left orbitofrontal cortex totalling 9 min. Tolerability and safety was evaluated using a standardised safety questionnaire. Neurocognitive functioning was examined using the Cambridge Neuropsychological Test Automated Battery and measures of verbal fluency from the Delis-Kaplan Executive Functioning TestTM at five time points over three months. RESULTS: The protocol was safe and tolerable. Frequencies of minor adverse effects were higher in active (17 endorsements) than sham (1 endorsement) conditions. No between group differences in neurocognitive functioning were identified over three months. COMPARISON WITH EXISTING METHOD: This study is the first to evaluate the feasibility of low and high frequency parameters applied sequentially in a single session to the three selected cortical regions whilst providing neurocognitive data. CONCLUSIONS: rTMS applied sequentially over three cortical regions was found to be safe and tolerable in healthy individuals with no major neurocognitive effects over three months. Such findings can be used to inform the development of rTMS protocols involving multi site stimulation for OCD. PMID- 26545443 TI - Vicarious social defeat stress: Bridging the gap between physical and emotional stress. AB - BACKGROUND: Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g., chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. NEW METHOD: By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. RESULTS: We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. COMPARISON WITH EXISTING METHOD(S): The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. CONCLUSIONS: The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice. PMID- 26545444 TI - A Review of the DASH Diet as an Optimal Dietary Plan for Symptomatic Heart Failure. AB - Despite tremendous focus, effort, drug and device development and resources dedicated to the care of patients at risk for and with heart failure (HF), the epidemic continues. The HF patient presents with a widely deranged physiology and typically at the same time is malnourished adding to the disease complexity and therapeutic challenges. Most nutritional approaches for patients with HF focus on dietary restrictions (of salt and water) and lack uniformity or clarity or focus on meeting nutritional needs, barriers and deficits of the patient with HF. Finally, it seems reasonable to anticipate that any dietary program recommendation should contribute in a positive way toward HF management goals and at its foundation positively contribute to the deranged physiology. In many ways the "Dietary Approaches to Stop Hypertension" (DASH) dietary program fulfills these needs and early evidence supports the notion that the DASH diet may be optimal for patients with HF. This brief review examines some of this evidence and provides recommendations for the HF community. PMID- 26545445 TI - Body Composition Indices and Single and Clustered Cardiovascular Disease Risk Factors in Adolescents: Providing Clinical-Based Cut-Points. AB - The aims of the present study in adolescents were 1) to examine how various body composition-screening tests relate to single and clustered cardiovascular disease (CVD) risk factors, 2) to examine how lean mass and body fatness (independently of each other) relate to clustered CVD risk factors, and 3) to calculate specific thresholds for body composition indices associated with an unhealthier clustered CVD risk. We measured 1089 European adolescents (46.7% boys, 12.5-17.49years) in 2006-2007. CVD risk factors included: systolic blood pressure, maximum oxygen uptake, homeostasis model assessment, C-reactive protein (n=748), total cholesterol/high density lipoprotein cholesterol and triglycerides. Body composition indices included: height, body mass index (BMI), lean mass, the sum of four skinfolds, central/peripheral skinfolds, waist circumference (WC), waist to-height ratio (WHtR) and waist-to-hip ratio (WHR). Most body composition indices are associated with single CVD risk factors. The sum of four skinfolds, WHtR, BMI, WC and lean mass are strong and positively associated with clustered CVD risk. Interestingly, lean mass is positively associated with clustered CVD risk independently of body fatness in girls. Moderate and highly accurate thresholds for the sum of four skinfolds, WHtR, BMI, WC and lean mass are associated with an unhealthier clustered CVD risk (all AUC>0.773). In conclusion, our results support an association between most of the assessed body composition indices and single and clustered CVD risk factors. In addition, lean mass (independent of body fatness) is positively associated with clustered CVD risk in girls, which is a novel finding that helps to understand why an index such as BMI is a good index of CVD risk but a bad index of adiposity. Moderate to highly accurate thresholds for body composition indices associated with a healthier clustered CVD risk were found. Further studies with a longitudinal design are needed to confirm these findings. PMID- 26545446 TI - Transdermal potential and anti-arthritic efficacy of ursolic acid from niosomal gel systems. AB - The aim of the present study was to optimize niosomes by experimental design for enhanced transdermal delivery of ursolic acid for the effective treatment of arthritis. The experimental design (3 factor 3 levels, Box-Behnken design) was used to study individual and combined effects of different formulation variables. The variables cholesterol (X1), span 60 (X2) and phospholipid (X3) were taken as independent factors and their effect was observed on size (Y1) entrapment efficiency (Y2), and transflux (Y3). The formulation composition with span 60 (85mg), cholesterol (12.3mg), and phospholipid (65mg) was found to fulfil requisites of optimized ursolic acid niosome formulation (URNF). URNF had shown vesicle size of 665.45nm, entrapment efficiency of 92.74% with transflux of 17.25MUg/cm(2)/h. The in vivo bioactivity showed that the prepared URNF-gel was able to provide good anti-arthritic activity due to enhanced permeation of UA through the skin and results were found to be comparable to standard gel (Omni gel). The radiographical image confirmed that, the developed URNF-gel was found to be effective to treat arthritis. Thus niosomal gel of ursolic acid would be a promising alternative to conventional therapy for safe and efficient treatment of arthritis and musculoskeletal disorders. PMID- 26545447 TI - The kindest cut: global need to increase vasectomy availability. PMID- 26545448 TI - Saving lives through improved use of ACTs. PMID- 26545449 TI - Optimum population-level use of artemisinin combination therapies: a modelling study. AB - BACKGROUND: Artemisinin combination therapies (ACTs) are used worldwide as first line treatment against confirmed or suspected Plasmodium falciparum malaria. Despite the success of ACTs at reducing the global burden of malaria, emerging resistance to artemisinin threatens these gains. Countering onset of resistance might need deliberate tactics aimed at slowing the reduction in ACT effectiveness. We assessed optimum use of ACTs at the population level, specifically focusing on a strategy of multiple first-line therapies (MFT), and comparing it with strategies of cycling or sequential use of single first-line ACTs. METHODS: With an individual-based microsimulation of regional malaria transmission, we looked at how to apply a therapy as widely as possible without accelerating reduction of efficacy by drug resistance. We compared simultaneous distribution of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine (ie, MFT) against strategies in which these ACTs would be cycled or used sequentially, either on a fixed schedule or when population-level efficacy reaches the WHO threshold of 10% treatment failure. The main assessment criterion was total number of treatment failures per 100 people per year. Additionally, we analysed the benefits of including a single non-ACT therapy in an MFT strategy, and did sensitivity analyses in which we varied transmission setting, treatment coverage, partner-drug half-life, fitness cost of drug resistance, and the relation between drug concentration and resistance evolution. FINDINGS: Use of MFT was predicted to reduce the long-term number of treatment failures compared with strategies in which a single first-line ACT is recommended. This result was robust to various epidemiological, pharmacological, and evolutionary features of malaria transmission. Inclusion of a single non-ACT therapy in an MFT strategy would have substantial benefits in reduction of pressure on artemisinin resistance evolution, delaying its emergence and slowing its spread. INTERPRETATION: Adjusting national antimalarial treatment guidelines to encourage simultaneous use of MFT is likely to extend the useful therapeutic life of available antimalarial drugs, resulting in long-term beneficial outcomes for patients. FUNDING: Wellcome Trust, UK Medical Research Council, Li Ka Shing Foundation. PMID- 26545450 TI - [Prescription of asthma action plans in the Aquitaine region of France]. AB - INTRODUCTION: Although guidelines recommend the prescription of written asthma action plans (WAAP), their use remains limited. METHODS: A prospective survey was performed from 2013 to 2014. We interviewed respiratory physicians, paediatric respiratory physicians and allergologists taking care of asthmatic patients and practicing in the Aquitaine region of France, using computerized questionnaires, regarding their everyday practice in the use of WAAP. RESULTS: A total of 59/143 (41%) clinicians, with a mean age of 47 years, participated in the study. A total of 41/59 (69.5%) were using a WAAP (12 different models with very inhomogeneous contents, mostly targeting symptoms only). WAAP prescribers were younger than non prescribers, were more often female, working mostly in the Gironde area, with mixed hospital and private-based activity, and were paediatric-respiratory physicians or respiratory physicians. The severity of asthma had little influence on WAAP prescriptions. CONCLUSION: In the Aquitaine region, prescription of WAAPs remains inadequate and shows large disparities. WAAP users are mostly younger female specialists. PMID- 26545451 TI - Reply. PMID- 26545452 TI - Editorial Comment. PMID- 26545453 TI - Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood. AB - PURPOSE: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. METHODS AND MATERIALS: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations through 2014 (median follow-up time: 48 months). RESULTS: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). CONCLUSIONS: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy. PMID- 26545454 TI - Developing an Evidence Review Cycle Model for Canadian Dietary Guidance. AB - Formulating dietary guidance involves navigating a large volume of substantive, conflicting evidence. Canada's guidance is determined after periodic evidence reviews. Health Canada identified the need for a more formal and systematic process to gather, assess, and analyze evidence. This led to the development of the Evidence Review Cycle model for Canada's dietary guidance. The Evidence Review Cycle consists of 5 steps that form a dynamic, iterative process to promote evidence-based, transparent, and proactive decision making. Resulting actions may include enhancing the implementation of guidance, revising guidance, or developing new guidance. Here, the development of this model is described, including considerations for implementation. PMID- 26545455 TI - Abnormal time course of low beta modulation in non-fluent preschool children: A magnetoencephalographic study of rhythm tracking. AB - Stuttering is a disorder of speech affecting millions of people around the world. Whilst the exact aetiology of stuttering remains unknown, it has been hypothesised that it is a disorder of the neural mechanisms that support speech timing. In this article, we used magnetoencephalography (MEG) to examine activity from auditory regions of the brain in stuttering and non-stuttering children aged 3-9years. For typically developing children, we found that MEG oscillations in the beta band responded to rhythmic sounds with a peak near the time of stimulus onset. In contrast, stuttering children showed an opposite phase of beta band envelope, with a trough of activity at stimulus onset. These results suggest that stuttering may result from abnormalities in predictive brain responses which are reflected in abnormal entrainment of the beta band envelope to rhythmic sounds. PMID- 26545456 TI - Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. AB - Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. PMID- 26545458 TI - Network pharmacology-based prediction of the active ingredients and potential targets of Mahuang Fuzi Xixin decoction for application to allergic rhinitis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Certain herbal formulae from Traditional Chinese Medicine (TCM) are effective for treating and preventing diseases in clinical practice. Mahuang fuzi Xixin Decoction (MFXD) is a TCM that is used to treat allergic rhinitis (AR); however, the active ingredients and potential targets of its action against AR remain unclear. Therefore, further investigation is required. METHODS: A network pharmacology approach comprising drug-likeness evaluation, oral bioavailability prediction, multiple drug target prediction, and network analysis has been used in this study. RESULTS: The comprehensive systematic approach was successfully to indentify 41 bioactive ingredients in MFXD, while 37 potential targets hit by these ingredients related to AR. Moreover, wherein four predicted ingredients possess anti-inflammatory effects were found by this technique. CONCLUSIONS: Our works successfully predict the active ingredients and potential targets of MFXD for application to allergic rhinitis and helps to illustrate mechanism of action on a systematic level. This study not only provides new insights into the chemical basis and pharmacology of MFXD but also demonstrates a feasible method for discovering potential drugs from herbal medicine. PMID- 26545457 TI - White matter and memory in healthy adults: Coupled changes over two years. AB - Numerous cross-sectional studies have used diffusion tensor imaging (DTI) to link age-related differences in white matter (WM) anisotropy and concomitant decrements in cognitive ability. Due to a dearth of longitudinal evidence, the relationship between changes in diffusion properties of WM and cognitive performance remains unclear. Here we examine the relationship between two-year changes in WM organization and cognitive performance in healthy adults (N=96, age range at baseline=18-79 years). We used latent change score models (LCSM) to evaluate changes in age-sensitive cognitive abilities - fluid intelligence and associative memory. WM changes were assessed by fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) in WM regions that are considered part of established memory networks and exhibited individual differences in change. In modeling change, we postulated reciprocal paths between baseline measures and change factors, within and between WM and cognition domains, and accounted for individual differences in baseline age. Although baseline cross sectional memory performance was positively associated with FA and negatively with RD, longitudinal effects told an altogether different story. Independent of age, longitudinal improvements in associative memory were significantly associated with linear reductions in FA and increases in RD. The present findings demonstrate the sensitivity of DTI-derived indices to changes in the brain and cognition and affirm the importance of longitudinal models for evaluating brain cognition relations. PMID- 26545460 TI - The diagnostic accuracy of CT-guided percutaneous core needle biopsy and fine needle aspiration in pulmonary lesions: a meta-analysis. AB - AIM: To determine and compare the diagnostic value of computed tomography (CT) guided percutaneous core needle biopsy (PCNB) and percutaneous fine-needle aspiration biopsy (PNAB) in pulmonary lesions. MATERIALS AND METHODS: PubMed, EMBASE, and the Web of Science were systematically searched for relevant studies that investigated the diagnostic accuracy of CT-guided PCNB and/or PNAB for pulmonary lesions up to December 2014. After study selection, data extraction, and quality assessment, the sensitivity (SEN), specificity (SPE), diagnostic odds rate (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and summary receiver operating characteristic (SROC) curves were calculated using the Meta-Disc 1.4 software. RESULTS: Nineteen publications, including 21 independent studies, met the inclusion criteria. Of them, 15 studies were included in the PCNB group and six studies in the PNAB group. The pooled SEN, SPE, DOR, PLR, NLR, and SROC were 0.95, 0.99, 54.72, 0.06, 821.90, and 0.98 in the PCNB group and 0.90, 0.99, 24.71, 0.14, 210.72, and 0.98 in the PNAB group, respectively. CONCLUSION: Based on current evidence, both PCNB and PNAB can be used as diagnostic methods to distinguish benign and malignant pulmonary lesions; the difference between PCNB and PNAB regarding diagnostic accuracy of benign or malignant pulmonary lesions is not obvious. PMID- 26545459 TI - Evaluation of kudzu root extract-induced hepatotoxicity. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Kudzu root, the root of Pueraria lobata (Willd.) Ohwi, has been used as food and medicine for centuries, but few studies indicate that kudzu root may cause liver damage. AIM OF STUDY: We studied the hepatotoxicity of kudzu root extract in mice, HepG2 cells and mice hepatocytes. MATERIALS AND METHODS: Mice were administrated with kudzu root extract (10mg/day) for 4 weeks, and then the biochemical analysis and histopathological changes were carried out. To explore the potential mechanism by which kudzu root extract induced hepatotoxicity, HepG2 cells and mice hepatocytes were co-cultured with kudzu root extract or puerarin, which is a kudzu root isoflavone, for 2h. RESULTS: The increase of serum ALT and AST and histopathological changes in treated mice revealed that kudzu root extract was hepatotoxic. The increase of LDH leakage for HepG2 cells and mice hepatocytes further confirmed hepatotoxicity of kudzu root extract. Kudzu root extract and puerarin significantly up-regulated Mt1 mRNA involved in the acute phase response and Bax which is crucial for apoptosis. Gclc, Nrf2 and Ho-1 mRNA expressions did not change in treatment group. CONCLUSIONS: Kudzu root extract may be hepatotoxic and caution may be required for its use. PMID- 26545461 TI - Use of computed tomography to assess volume change after endoscopic orbital decompression for Graves' ophthalmopathy. AB - BACKGROUND: Orbital decompression is frequently performed in the management of patients with sight-threatening and disfiguring Graves' ophthalmopathy. The quantitative measurements of the change in orbital volume after orbital decompression procedures are not definitively known. Furthermore, the quantitative effect of septal deviation on volume change has not been previously analyzed. OBJECTIVES: To provide quantitative measurement of orbital volume change after medial and inferior endoscopic decompression and describe a straightforward method of measuring this change using open-source technologies. A secondary objective was to assess the effect of septal deviation on orbital volume change. METHODS: A retrospective review was performed on all patients undergoing medial and inferior endoscopic orbital decompression for Graves' ophthalmopathy at a tertiary care academic medical center. Pre-operative and post operative orbital volumes were calculated from computed tomography (CT) data using a semi-automated segmenting technique and OsirixTM, an open-source DICOM reader. Data were collected for pre-operative and post-operative orbital volumes, degree of septal deviation, time to follow-up scan, and individual patient Hertel scores. RESULTS: Nine patients (12 orbits) were imaged before and after decompression. Mean pre-operative orbital volume was 26.99 cm(3) (SD=2.86 cm(3)). Mean post-operative volume was 33.07 cm(3) (SD=3.96 cm(3)). The mean change in volume was 6.08 cm(3) (SD=2.31 cm(3)). The mean change in Hertel score was 4.83 (SD=0.75). Regression analysis of change in volume versus follow-up time to imaging indicates that follow-up time to imaging has little effect on change in volume (R=-0.2), and overall mean maximal septal deviation toward the operative side was -0.5mm. Negative values were attributed to deviation away form the operative site. A significant correlation was demonstrated between change in orbital volume and septal deviation distance site (R=0.66), as well as between change in orbital volume and septal deviation angle (R=0.67). Greater volume changes were associated with greater degree of septal deviation away from the surgical site, whereas smaller volume changes were associated with greater degree of septal deviation toward the surgical site. CONCLUSION: A straightforward, semi automated segmenting technique for measuring change in volume following endoscopic orbital decompression is described. This method proved useful in determining that a mean increase of approximately 6 cm in volume was achieved in this group of patients undergoing medial and inferior orbital decompression. Septal deviation appears to have an effect on the surgical outcome and should be considered during operative planning. PMID- 26545462 TI - Predictive value of E-cadherin and Ep-CAM in cervical lymph node metastasis of supraglottic larynx carcinoma. AB - OBJECTIVE: To evaluate the value of E-cadherin and epithelial cell adhesion molecule (Ep-CAM) expression in laryngeal biopsy materials for predicting cervical lymph node metastasis in patients with supraglottic laryngeal carcinoma. METHODS: All patients participating in the study were selected from among the surgically treated patients at the department of Otolaryngology, Head and Neck Surgery, Erciyes University School of Medicine between 1991 and 2005. The study consisted of thirty patients who had pathologically metastatic lymph nodes (pN+ group) and 30 age-, sex-, T value- and differentiation matched patients without pathologically metastatic lymph nodes (pN0 group). Immunohistochemical studies were performed with E-cadherin and Ep-CAM antibodies on representative tumor sections collected from paraffin sections of laryngeal biopsy materials. The expression of E-cadherin and Ep-CAM was compared between the pN0 and pN+ groups. The association between immunostaining of E-cadherin and Ep-CAM was also evaluated. RESULTS: There was no significant difference between the two groups in terms of E-cadherin and Ep-CAM expression. There was also a very poor agreement between the expression of E-cadherin and Ep-CAM. CONCLUSION: Multi-institutional and multidisciplinary immunohistochemical studies conducted with standardized methodology and also with more patient participation may help to obtain more specific results. PMID- 26545463 TI - A pediatric case of mammary analogue secretory carcinoma within the parotid. AB - Mammary analogue secretory carcinoma (MASC) is a recently described entity in the differential diagnosis of salivary gland tumors. It is notable for a characteristic t(12;15)(p13;q25) translocation that results in a unique fusion protein, ETV6-NTRK3. While several studies have retrospectively identified this translocation in cases previously diagnosed as a different salivary malignancy, there have been relatively few cases where this translocation was identified on initial pathology results, and fewer still in a pediatric population. We present a case of a 15 year old female with a slowly enlarging, painless, left facial mass. MRI demonstrated a cystic mass extending into the deep lobe of the parotid, and she underwent parotidectomy. The tumor cells stained positive for S100 and CK19. ETV6 translocation was present, confirming the diagnosis. Mammary analogue secretory carcinoma is a recently described tumor of the salivary glands, which often masquerades as more common primary salivary gland tumors and cysts. More research is needed to characterize the typical behavior of this neoplasm and the optimal treatment regimen. With identification of its characteristic translocation, mammary analogue secretory carcinoma can be easily differentiated from its more prevalent counterparts, and should therefore remain within the differential of the pathologist and head and neck surgeon. PMID- 26545464 TI - Is routine pre-operative cardiac evaluation necessary in obese children undergoing adenotonsillectomy for OSA? AB - BACKGROUND: Adenotonsillectomy (T&A) is a common surgery performed for obstructive sleep apnea (OSA) in children. Obese children are at increased risk for OSA, but are also at increased risk for cardiovascular changes that might heighten their risk of undergoing a general anesthetic. There is currently no standard of care recommendation for cardiac workup prior to T&A. PURPOSE: To ascertain whether a preoperative cardiac workup is predictive of postoperative complications in obese children undergoing T&A for OSA. DESIGN: Retrospective cohort review. MATERIAL AND METHODS: 241 children with BMI >= 25 kg/m(2) underwent T&A for OSA. This cohort was divided into three groups - those who had no preoperative cardiac evaluation, those who had a preoperative cardiac evaluation but no significant findings and those who had a preoperative cardiac evaluation with at least one significant finding. Postoperative cardiac-related complications were compared between the three groups. RESULTS: There were significantly more postoperative complications in Group 3, the group with findings on preoperative cardiac evaluation. However, these were heavily weighted toward "hospital stay > 24 hours" without clear cardiac sequelae. Notably there were no incidents of pulmonary edema, re-intubation postoperatively or death. CONCLUSION: In obese children undergoing T&A at a tertiary care center, a preoperative cardiac workup was not shown to be beneficial in predicting postoperative complications. PMID- 26545465 TI - Trans-tympanic catheter insertion for treatment of patulous eustachian tube. AB - OBJECTIVES: To evaluate the safety and therapeutic efficacy of trans-tympanic catheter insertion (TCI) in patients with refractory patulous eustachian tube (PET). METHODS: TCI was attempted in thirty-six ears of twenty-nine patients with chronic PET refractory to conservative treatment. The catheter was inserted under local anesthesia in an operating room through the bony orifice of the eustachian tube (ET) to occlude the isthmus of the tube via a myringotomy site on the tympanic membrane. Patients were evaluated postoperatively by nasal endoscopy and by interview to document symptoms. Successful treatment was defined as complete relief or significant improvement plus satisfaction with treatment. Patients had no concurrent disease and did not undergo any additional surgical procedure. RESULTS: TCI was performed in all except one ear, in which it failed because of an abnormally narrow tympanic ET orifice. Follow-up durations ranged from 6 to 37 months, with an average of 19.3 months. Successful treatment of subjective autophony was achieved in twenty-nine (82.4%) of the thirty-five ears. Ventilation tube (VT) placement was performed in the two ears because of otitis media with effusion (OME) after TCI. In one ear, the inserted catheter was finally removed due to additional unilateral mastoiditis after VT extrusion. CONCLUSION: TCI seems to be a minimally invasive and was used successfully to treat PET. The procedure had a good overall success rate and complications were rare in the long-term. PMID- 26545466 TI - Case presentation and images of a lingual osseous choristoma in a pediatric patient. AB - Since its original description in 1913, fewer than 100 lingual osseous choristomas have been reported in the literature; thus, prevalence is unknown. We describe a case of an 11 year old male who was seen in consultation after an incidental left posterior tongue mass was discovered on exam. The patient's presentation of an asymptomatic, hard, pedunculate posterior tongue lesion is typical; however, if one is to believe the proposed congenital remnant theory in regards to the etiology of this benign tumor, it is curious that no mention was made of a lesion of the tongue on prior evaluations by his pediatrician or on the otolaryngologic examinations performed 3 and 6 years prior to the most recent presentation. Included with the case description are interesting radiographs, intra-operative photos, gross specimen photo and microscopic images. PMID- 26545467 TI - Survival of T4aN0 and T3N+ laryngeal cancer patients: a retrospective institutional study and systematic review. AB - OBJECTIVE: We aim to assess the correlation of tumor and nodal staging to survival in pT3N+ and T4aN0 laryngeal cancer with subgroup analysis within stage IVa (pT4N0 and pT3N2). STUDY DESIGN: Retrospective cohort study with systematic review of the literature. SETTING: Hotel Dieu de France University Hospital (tertiary referral center). SUBJECTS AND METHODS: Laryngeal cancer patients' registries were reviewed from 1998 to 2012 selecting pT3N+ and pT4aN0 patients treated by primary total layngectomy. Overall survivals were compared using Log rank and Kaplan-Meier analysis. A systematic review was performed by 2 reviewers including all the articles reporting the outcome of these categories of patients. Online databases, including PubMed and EMBASE, were used. Reference sections of identified studies were examined for additional articles. RESULTS: Thirteen T3N+ patients and 19 T4aN0 patients treated by primary total laryngectomy were included. Five-year overall survival for T3N+, T3N2 and T4aN0 was respectively 33%, 32.1% and 73.7%. Due to the small sample, the difference was not significant. The systematic review revealed three articles reporting overall survival outcome for the T4N0 group and 6 articles for the T3N+. At 5years, the survival ranged from 62.5% to 73% in T4N0 and from 32.2% to 77% in T3N+. CONCLUSION: In advanced stage laryngeal cancer, T4aN0 tends toward a better survival than T3N+ especially when compared to T3N2 although they are grouped in the same TNM stage IVa. PMID- 26545468 TI - Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma. AB - PURPOSE: The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. MATERIALS AND METHODS: After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. RESULTS: Ad-p14(ARF) combining with Ad antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. CONCLUSION: Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided. PMID- 26545470 TI - Delayed recurrence of sinonasal rhinosporidiosis. PMID- 26545469 TI - A rare location for sarcoma metastasis: The temporal bone. AB - Skeletal sarcoma metastasis is relatively rare; moreover, for this type of metastasis, the temporal bone is also a rare location. The temporal bone appears to be affected by metastatic tumors in discrete histopathologic patterns, with characteristic clinical presentations. In this study, we analyzed the records of 6 patients with skeletal sarcoma metastasis to the temporal bone, with an emphasis on histopathologic sections of human temporal bones. The most common site of sarcoma metastasis in the temporal bone was petrous apex in our series. Physicians should keep in mind that a sarcoma patient may manifest with ear findings due to temporal bone metastasis. PMID- 26545471 TI - What is the optimal diagnostic pathway in tuberculous lymphadenitis in the face of increasing resistance: Cytology or histology? AB - BACKGROUND: The London Borough of Newham has the highest rates of tuberculosis (TB) within Europe (116 per 100,000). There is a lack of guidance in lymph node (LN) TB on how to best obtain a positive culture, which is the gold standard in the face of increasing mycobacterial resistance. METHODS: An individual cohort study was carried out via a prospective local TB database capturing 90 cases of cervical LN TB over 34 months. We compared the diagnostic efficacy of fine needle aspiration (FNA) and excision biopsy of LN. RESULTS: FNA cytology revealed granulomata in 49%, acid-fast bacilli (AFB) in 8.6% and a positive culture in 40%. LN excision showed granulomata in 97.6%, AFB in 17.1% and a positive culture in 70.1%. There was an 18% resistance to first-line antimicrobials. CONCLUSIONS: We describe our experience and suggest an algorithm for the culture of TB organisms to avoid a lengthy diagnostic process. PMID- 26545472 TI - In vitro analysis of a novel controlled release system designed for intratympanic administration of N-acetylcysteine: a preliminary report. AB - The aim of this in-vitro experimental study was to design a novel drug delivery system that may permit controlled release of N-acetylcysteine (NAC) following intratympanic administration. The system was composed of two different solutions that attained a hydrogel form within seconds after getting into contact with each other. The authors performed swelling, pH and temperature tests and analysis of controlled release of NAC from this novel controlled release system. For the structure and porosity analysis of the hydrogel, an environmental scanning electron microscope (SEM) was used. The diameter of designed hydrogel showed an increase when pH was increased. In addition, in comparison to acidic values, the pore diameter of the hydrogel increased significantly especially in physiological level. The increase in the pore diameter was also directly proportional to the increase in temperature. Spectrophotometric analysis showed that the amount of NAC released into the medium was statistically significant (p=0.038, t=-2.18, 95% CI; DF: 27). SEM analysis of the samples revealed a smooth surface topography and numerous porous structures. The authors are of the opinion that the designed hydrogel may be used as an alternative method for intratympanic delivery of NAC for otoprotective purposes. The disadvantages of intratympanic injection of the drug in its liquid form, including leakage through eustachian tube, restraining the patient in an uncomfortable position, necessity for repetitive injections and dose dependent inflammation of the middle ear epithelium, may also be avoided. Further in vivo studies should be conducted to assess its tolerability and effectivity. PMID- 26545473 TI - Utility of basic fibroblast growth factor in the repair of blast-induced total or near-total tympanic membrane perforations: A pilot study. AB - OBJECTIVE: A pilot study was performed to investigate the utility of basic fibroblast growth factor (bFGF) in the repair of blast-induced total or near total tympanic membrane perforations (TMPs). STUDY DESIGN: Prospective clinical study. SETTING: Tertiary university hospital. SUBJECTS AND METHODS: Patients who fulfilled the inclusion criteria were treated with 0.10-0.15 mL of bFGF solution applied directly to total or near-total TMPs once daily until the perforations closed or for a maximum of 6 months. The treatment response was monitored via serial otoendoscopy, and audiometric outcomes were evaluated. RESULTS: Complete TMP closure was achieved in 16 of 17 patients with a blast-induced total or near total TMP. The mean closure time was 28.4 +/- 10.9 days. The improvement in hearing from pre- to post-treatment was statistically significant. There were no complications or adverse outcomes. CONCLUSIONS: The direct application of bFGF to blast-induced total or near-total TMPs is a promising, minimally invasive alternative to conventional tympanoplasty, with a comparable success rate. As reported in the literature, the closure rate was higher than achieved with spontaneous healing. There was no effect of the inverted edge on healing outcome. The use of bFGF in this setting has immediate therapeutic applications for military personnel with blast-induced TMPs who are stationed in isolated, remote environments. PMID- 26545474 TI - High rate of bilaterality in internal auditory canal metastases. AB - PURPOSE: Presentation of three cases of metastatic carcinoma to the internal auditory canal bilaterally, as well as a systematic review of the literature regarding the characteristics of these lesions. MATERIALS AND METHODS: Using a MEDLINE Ovid search (1946-2015), we identified and reviewed 102 cases of metastatic carcinoma to the internal auditory canal. Metrics recorded include: patient age, sex, tumor type, laterality, past oncologic history, co-occurring metastatic sites, clinical findings, radiographic findings, therapy received, and outcome. Cases of unilateral versus bilateral IAC were compared. RESULTS: Remarkably, 52.9% reported cases of internal auditory canal metastases have bilateral occurrence. The most common primary tumor sites for internal auditory canal metastases were lung (21.2%), skin (18.6%), and breast (16.7%), with lung and skin cancers having the highest rates of bilateral metastasis. Meningeal metastasis occurred at a much higher rate in bilateral cases (47.2%) versus unilateral cases (8.5%). Brain parenchymal metastasis also occurred at a higher rate in bilateral cases (38.2%) versus unilateral cases (19.2%). Outcomes for cases of internal auditory canal metastases are generally poor, with 56.3% of unilateral cases and 86.1% of bilateral cases reporting patient death within 5 years from diagnosis. CONCLUSIONS: In cases of internal auditory canal metastasis, clinicians should carefully assess for not only contralateral disease but also additional metastatic disease of the central nervous system. Rapid-onset hearing loss, tinnitus, vertigo, or facial palsy should raise suspicion for internal auditory canal metastasis, particularly in patients with a known oncologic history. PMID- 26545475 TI - Delayed facial palsy after tympanomastoid surgery: A report of 15 cases. AB - OBJECTIVE: To analyze potential etiology and outcomes of delayed facial palsy (DFP) after tympanomastoid surgery. METHODS: Fifteen cases of DFP out of 1582 cases after tympanomastoid surgery were reviewed, and the potential causes and outcomes were analyzed. RESULTS: 9 out of 15 patients (60%) had fallopian canal dehiscence and facial nerve exposure in contrast to 323 of 1567 patients (20.6%) without DFP, with significant difference (P<0.01). Chorda tympani was cut or overstretched in 4 cases. There were two cases with herpes labialis and IgM antibody against varicella-zoster virus. All patients fully recovered within two months. CONCLUSION: Fallopian canal dehiscence and facial nerve exposure was a risk factor of DFP after tympanomastoid surgery, and chorda tympani injury and viral reactivation may be triggering factors of DFP. The outcomes DFP after tympanomastoid surgery were excellent. PMID- 26545476 TI - Primary tuberculosis of thyroid. AB - Tuberculosis (TB) of the thyroid gland, either in its primary or secondary form, is an extremely rare occurrence. It is infrequent even in countries with high incidence and prevalence of pulmonary and extrapulmonary TB. We report here a case of primary tuberculosis of thyroid presenting to us with sudden onset thyroid swelling since 20 days. PMID- 26545477 TI - Tinnitus management with percutaneous osseointegrated auditory implants for unilateral sensorineural hearing loss. AB - OBJECTIVE: To determine the effects, if any, of percutaneous osseointegrated auditory implants (OAI) on tinnitus in patients with unilateral SNHL. STUDY DESIGN: Prospective cohort series. SETTING: Tertiary academic referral center, single surgeon. PATIENTS: Adult OAI recipients with unilateral severe to profound sensorineural hearing loss (SNHL) in the implanted ear. INTERVENTION: Percutaneous OAI. MAIN OUTCOME MEASURE(S): The Tinnitus Reaction Questionnaire (TRQ) and the Tinnitus Handicap Inventory (THI) were recorded pre-implantation, and at 6 and 12 months following device activation. RESULTS: Ten eligible patients were enrolled. The mean pre-operative TRQ and THI scores for all subjects were 32.80 +/- 23.41 and 37.00 +/- 22.75, respectively. Both scores decreased 6 months after device activation, with TRQ mean of 19.67 +/- 21.73 (p=0.0012) and THI mean of 27.11 +/- 23.41 (NS). After 12 months, the downward trend continued with TRQ mean of 17.30 +/- 20.67 (p=0.0008) and THI mean of 21.70 +/- 23.02 (p=0.0116). Subgroup analysis comparing patients with severe SNHL to those with profound SNHL demonstrated a decrease in TRQ and THI scores at 12 months for both groups, but it was only statistically significant for the severe SNHL group (n=7). CONCLUSIONS: OAI use in SSD is associated with a statistically significant decrease in tinnitus as measured by the TRQ and THI. The reasons for this are likely multifactorial, though possibly due to stimulation of residual cochlear function in the SSD ear. Further study of a larger cohort is ongoing. PMID- 26545478 TI - Provider and patient drivers of ototopical antibiotic prescription variability. AB - OBJECTIVE: To determine if providers prescribe more affordable topical antibacterial therapy for patients who are economically disadvantaged or come from economically disadvantaged communities. STUDY DESIGN: Prescription drug database review. SETTING: Large academic hospital network. SUBJECTS AND METHODS: Ototopical prescription records of 2416 adults and children presenting with acute and chronic otologic infections from 2009 to 2013 were reviewed. Prescription, patient, provider, and institution variables including diagnosis, prescription type, demographics, health insurance status, healthcare provider type and setting were analyzed. RESULTS: Otitis externa and acute otitis media were the most common diagnoses. Non-OHNS (Otolaryngology-Head and Neck Surgery) providers served 82% of all patients. OHNS providers prescribed proportionally less fluoroquinolone, and more brand-name antibiotics compared to non-OHNS providers. Adults were more likely to receive a non-fluoroquinolone antibiotic and a generic prescription versus pediatric patients. Patients who self-identified as 'white' ethnicity received proportionally more fluoroquinolone prescriptions than patients who identified as 'non-white,' but there was no difference in provider type. The proportion of fluoroquinolone prescriptions was significantly higher in patients from low-poverty counties, however poverty level was not associated with patients seeing a particular provider type. The majority of our patients had commercial insurance, followed by Medicaid. Medicare patients had the lowest proportion of fluoroquinolone antibiotic prescriptions, and were less likely to receive fluoroquinolone prescriptions versus commercial insurance. Non-insured patients received proportionally more generic versus brand prescriptions than insured patients. CONCLUSION: Our results indicate potential provider, patient demographic, and financial factors producing considerable variability in the prescribing patterns for topical antibiotics for common otologic infections. PMID- 26545479 TI - Removal of the split thickness skin graft from the skin paddle of the donor site: A single institution's experience. AB - PURPOSE: Radial forearm free flaps (RFFFs) and fibular osteocutaneous flaps (FOFs) are mainstays of head and neck reconstruction. Removal of the donor tissue often leaves a soft tissue defect requiring a split thickness skin graft (STSG) for coverage. The purpose of this study is to evaluate the potential to reduce the morbidity of removal of the STSG from a second site. MATERIALS AND METHODS: We report a series of 9 patients who had the STSG taken from the free flap donor skin paddle as an alternative to removal from the standard distant sight. RESULTS: 9/9 (100%) flaps were successfully transferred with no primary or secondary loss of the flap. 8/9 (89%) of STSGs were successfully harvested from the donor skin paddle. Postoperative complications included infection and partial STSG loss (2/9, 22%). CONCLUSIONS: This study demonstrates the feasibility and reduced morbidity associated with removal of the STSG from the donor flap skin paddle in addition to the placement of a de-epithelialized free flap in head and neck reconstruction patients. Given this research, which supports the previously published research on this topic, this technique could be considered in an effort to reduce morbidity in patients undergoing head and neck reconstruction using the RFFF and FOF. PMID- 26545480 TI - Correlation between the dizziness handicap inventory and balance performance during the acute phase of unilateral vestibulopathy. AB - PURPOSE: The dizziness handicap inventory (DHI) is widely used to evaluate self perceived handicap due to dizziness, and is known to correlate with vestibular function tests in chronic dizziness. However, whether DHI reflects subjective symptoms during the acute phase has not been studied. This study aims to investigate the correlations of subjective and objective measurements to highlight parameters that reflect the severity of dizziness during the first week of acute unilateral vestibulopathy. MATERIALS AND METHODS: Thirty-seven patients with acute unilateral vestibulopathy were examined. Patients' subjective perceptions of dizziness were measured using the DHI, Vertigo Visual Analog Scale (VVAS), Disability Scale (DS), and Activity-Specific Balance Scale (ABC). Additionally, the oculomotor tests, Romberg and sharpened Romberg tests, functional reach test, and dynamic visual acuity tests were performed. The correlation between the DHI and other tests was evaluated. RESULTS: DHI-total scores exhibited a moderately positive correlation with VVAS and DS, and a moderately negative correlation with ABC. However, DHI-total score did not correlate with results of the Romberg, sharpened Romberg, or functional reach tests. When compared among four groups divided according to DHI scores, VVAS and DS scores exhibited statistically significant differences, but no significant differences were detected for other test results. CONCLUSION: Our findings revealed that the DHI correlated significantly with self-perceived symptoms measured by VVAS and DS, but not ABC. There was no significant correlation with other balance function tests during the first week of acute vestibulopathy. The results suggest that DHI, VVAS and DS may be more useful to measure the severity of acute dizziness symptoms. PMID- 26545481 TI - Orbital compartment syndrome during endoscopic drainage of subperiosteal orbital abscess. AB - BACKGROUND: Orbital compartment syndrome is a rare ocular emergency requiring immediate intervention to prevent vision loss. It can arise due to a variety of causes including trauma, neoplasms and retrobulbar hemorrhage during endoscopic sinus surgery. Lateral canthotomy and inferior cantholysis is a well-known therapeutic procedure to rapidly relieve raised intraocular pressures. CASE REPORT: We report a case of a subperiosteal orbital abscess due to acute maxillary sinusitis that underwent endoscopic drainage. Intraoperatively, he developed raised intraocular pressure following irrigation of the maxillary sinus and manual pressure on the malar abscess, necessitating emergent lateral canthotomy and inferior cantholysis. CONCLUSION: To our knowledge, this is the first reported case of orbital compartment syndrome following sinonasal irrigation and malar pressure in the English literature. This case will serve as a reminder to the sinus surgeon of the potential danger of transmitted pressure from the paranasal sinus or malar soft tissue into the orbital compartment. PMID- 26545482 TI - Effect of mastoid drilling on the distortion product otoacoustic emissions in the non operated ear. AB - OBJECTIVE: To monitor the effect of mastoid drilling on the non-operated ear distortion product otoacoustic emissions. MATERIALS AND METHODS: Distortion product otoacoustic emissions (DPOAEs) were measured at frequencies of f 2=2, 3, 4 and 5 kHz, and a frequency ratio f 1 /f 2=1.22. DPOAEs were measured in 49 cases, pre and post-operatively who underwent mastoid drilling procedures, compared with each other and with 49 controls who underwent myringoplasty and myringotomy procedures. RESULTS: Amplitudes of DPOAEs decreased significantly in those who underwent mastoidectomies over all the measured frequencies in the immediate post-operative period but had recovered by the seventh post operative day. CONCLUSION: Drill induced noise can cause temporary decrease in the DPOAEs postoperatively and hence temporary hearing loss for a period of one week. PMID- 26545483 TI - A novel vasorelaxant lectin purified from seeds of Clathrotropis nitida: partial characterization and immobilization in chitosan beads. AB - A novel lectin from seeds of Clathrotropis nitida (CNA) was purified and characterized. CNA is a glycoprotein containing approximately 3.3% carbohydrates in its structure. CNA promoted intense agglutination of rabbit erythrocytes, which was inhibited by galactosides and porcine stomach mucin (PSM). The lectin maintained its hemagglutinating activity after incubation in a wide range of temperatures (30-60 degrees C) and pH (6.0-7.0), and its binding activity was dependent on divalent cations (Ca(+2) and Mg(+2)). SDS-PAGE showed an electrophoretic profile consisting of a single band of 28 kDa, as confirmed by electrospray ionization mass spectrometry, which indicated an average molecular mass of 27,406 +/- 2 Da and the possible presence of isoforms and glycoforms. In addition, CNA exhibited no toxicity to Artemia sp. nauplii and elicited reversible and dose-dependent vasorelaxation in precontracted aortic rings. CNA was successfully immobilized on chitosan beads and was able to capture PSM in solution. This study demonstrated that CNA is a lectin that has potential as a biotechnological tool in glycomics and glycoproteomics applications. PMID- 26545484 TI - Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. AB - The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDMTM)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug loaded implantable prototypes. PMID- 26545485 TI - Roller compaction scale-up using roll width as scale factor and laser-based determined ribbon porosity as critical material attribute. AB - Due to the complexity and difficulties associated with the mechanistic modeling of roller compaction process for scale-up, an innovative equipment approach is to keep roll diameter fixed between scales and instead vary the roll width. Assuming a fixed gap and roll force, this approach should create similar conditions for the nip regions of the two compactor scales, and thus result in a scale reproducible ribbon porosity. In the present work a non-destructive laser-based technique was used to measure the ribbon porosity at-line with high precision and high accuracy as confirmed by an initial comparison to a well-established volume displacement oil intrusion method. The ribbon porosity was found to be scale independent when comparing the average porosity of a group of ribbon samples (n=12) from small-scale (Mini-Pactor(r)) to large-scale (Macro-Pactor(r)). A higher standard deviation of ribbons fragment porosities from the large-scale roller compactor was attributed to minor variations in powder densification across the roll width. With the intention to reproduce ribbon porosity from one scale to the other, process settings of roll force and gap size applied to the Mini-Pactor(r) (and identified during formulation development) were therefore directly transferrable to subsequent commercial scale production on the Macro Pactor(r). This creates a better link between formulation development and tech transfer and decreases the number of batches needed to establish the parameter settings of the commercial process. PMID- 26545486 TI - Mechanism Matters: A Taxonomy of Cell Penetrating Peptides. AB - The permeability barrier imposed by cellular membranes limits the access of exogenous compounds to the interior of cells. Researchers and patients alike would benefit from efficient methods for intracellular delivery of a wide range of membrane-impermeant molecules, including biochemically active small molecules, imaging agents, peptides, peptide nucleic acids, proteins, RNA, DNA, and nanoparticles. There has been a sustained effort to exploit cell penetrating peptides (CPPs) for the delivery of such useful cargoes in vitro and in vivo because of their biocompatibility, ease of synthesis, and controllable physical chemistry. Here, we discuss the many mechanisms by which CPPs can function, and describe a taxonomy of mechanisms that could be help organize future efforts in the field. PMID- 26545488 TI - A comparative study of proliferative activity and tumor stage of pregnancy associated melanoma (PAM) and non-PAM in gestational age women. AB - BACKGROUND: The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. OBJECTIVE: We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). METHODS: In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. RESULTS: In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. LIMITATIONS: This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. CONCLUSIONS: In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies. PMID- 26545489 TI - Biomarker responses to estrogen and androgen exposure in the brook stickleback (Culaea inconstans): A new bioindicator species for endocrine disrupting compounds. AB - Small-bodied freshwater fish are commonly used in regulatory testing for endocrine disrupting compounds (EDCs) but most lack a sensitive and quantifiable androgen-specific biomarker. Brook stickleback (Culaea inconstans) are a North American freshwater fish whose males produce an androgen-regulated glycoprotein in the kidney called spiggin. Although spiggin induction in females has been used as an androgen-specific biomarker of exposure in other stickleback species it has not been characterized in brook stickleback. Therefore, our objective was to develop a bioassay using brook stickleback to measure estrogenic and androgenic responses and establish the sensitivity of traditional and novel biomarkers of exposure. We first developed and optimized a qPCR assay to measure spiggin and vitellogenin transcript levels in kidney and liver tissue, respectively. Basal levels were differentially expressed in mature wild-caught male and female brook stickleback. To determine their sensitivity to EDCs, fish were exposed to nominal concentrations of 1, 10 and 100ng/L of 17alpha-methyltestosterone (MT) or 17alpha ethinylestradiol (EE2) for 21days (sampled at 7 and 21days) under semi-static renewal conditions. MT and EE2 exposure induced spiggin and vitellogenin transcripts in female kidneys and male livers, respectively. Exposure to EE2 also increased hepatosomatic index in both sexes and decreased gonadosomatic index in females. Histopathological alterations were observed in the kidney of EE2-exposed fish and an increase in kidney epithelium cell height occurred in MT-exposed females. Given the sensitivity of these endpoints, the brook stickleback is a promising new freshwater fish model for EDC evaluation and a potential bioindicator for EDCs in North American freshwater environments. PMID- 26545490 TI - The activity of detoxifying enzymes in the infective juveniles of Heterorhabditis bacteriophora strains: Purification and characterization of two acetylcholinesterases. AB - The infectivity and detoxifying enzyme activities including glutathione-S transferase (GST), acetylcholinesterase (AChE) and carboxylesterase (CaE) are investigated in the infective juveniles (IJs) of six different strains of Heterorhabditis bacteriophora as a biocontrol agent against insect pests. The specific activities ranged from 10.8-29.8 and 50-220units/mg protein for GST and AChE, respectively; and from 24.7-129 and 22.6-77.3units/mg protein for CaE as estimated by P-nitrophenyl and alpha-naphthyl acetates, respectively. H. bacteriophora EM2 strain has the highest infectivity and the highest enzymatic activities as well. AChE is the predominant detoxifying enzyme that might imply its major role in the detoxification of insecticide(s). The isoenzyme pattern demonstrated two major slow-moving isoforms in all EPN strains examined. Purification of two AChE isoforms, AChEAII and AChEBI, from H. bacteriophora EM2 strain is performed by ammonium sulfate precipitation, gel filtration on Sephacryl S-200 and chromatography on DEAE-Sepharose. AChEAII and AChEBII have specific activities of 1207 and 1560unit/mg protein, native molecular weights of 180 and 68kDa, and are found in dimeric and monomeric forms, respectively. Both isoforms showed optimum activity at pH8.5 and 35 degrees C. AChEBI exhibited higher thermal stability and higher activation energy than AChEAII. The enzymatic activities of purified AChEs are completely inhibited by Hg(+2) and Ni(+2) and greatly enhanced by Mn(+2). The substrate specificity, the relative efficiency of substrates hydrolysis, substrate inhibition and inhibition by BW284C51, but not by iso-OMPA, clearly indicated that they are true AChEs; their properties are compared with those recorded for insects as target hosts for H. bacteriophora EM2. PMID- 26545491 TI - HPLC & NMR-based forced degradation studies of ifosfamide: The potential of NMR in stability studies. AB - PURPOSE: The aim of this study is to conduct a forced degradation study on ifosfamide under several stress conditions to investigate the robustness of the developed HPLC method. It also aims to provide further insight into the stability of ifosfamide and its degradation profile using both HPLC and NMR. METHODS: Ifosfamide solutions (20mg/mL; n=15, 20mL) were stressed in triplicate by heating (70 degrees C), under acidic (pH 1 & 4) and alkaline (pH 10 & 12) conditions. Samples were analysed periodically using HPLC and FT-NMR. RESULTS AND DISCUSSION: Ifosfamide was most stable under weakly acidic conditions (pH 4). NMR results suggested that the mechanism of ifosfamide degradation involves the cleavage of the PN bond. For all stress conditions, HPLC was not able to detect ifosfamide degradation products that were detected by NMR. CONCLUSION: These results suggest that the developed HPLC method for ifosfamide did not detect the degradation products shown by NMR. It is possible that degradation products co-elute with ifosfamide, do not elute altogether or are not amenable to the detection method employed. Therefore, investigation of ifosfamide stability requires additional techniques that do not suffer from the aforementioned shortcomings. PMID- 26545487 TI - Modeling mania in preclinical settings: A comprehensive review. AB - The current pathophysiological understanding of mechanisms leading to onset and progression of bipolar manic episodes remains limited. At the same time, available animal models for mania have limited face, construct, and predictive validities. Additionally, these models fail to encompass recent pathophysiological frameworks of bipolar disorder (BD), e.g. neuroprogression. Therefore, there is a need to search for novel preclinical models for mania that could comprehensively address these limitations. Herein we review the history, validity, and caveats of currently available animal models for mania. We also review new genetic models for mania, namely knockout mice for genes involved in neurotransmission, synapse formation, and intracellular signaling pathways. Furthermore, we review recent trends in preclinical models for mania that may aid in the comprehension of mechanisms underlying the neuroprogressive and recurring nature of BD. In conclusion, the validity of animal models for mania remains limited. Nevertheless, novel (e.g. genetic) animal models as well as adaptation of existing paradigms hold promise. PMID- 26545492 TI - Classification tree analysis of postal questionnaire data to identify risk of excessive gestational weight gain. AB - OBJECTIVE: overweight/obese weight status during pregnancy increases risk of a range of adverse health outcomes for mother and child. Whereas identification of those who are overweight/obese pre-pregnancy and in early pregnancy is straightforward, prediction of who will experience excessive gestational weight gain (EGWG), and thus be at greater risk of becoming overweight or obese during pregnancy is more challenging. The present study sought to better identify those at risk of EGWG by exploring pre-pregnancy BMI as well as a range of psychosocial risk factors identified as risk factors in prior research. METHODS: 225 pregnant women completed self-reported via postal survey measures of height, weight, and psychosocial variables at 16-18 weeks gestation, and reported their weight again at 32-34 weeks to calculate GWG. Classification and regression tree analysis (CART) was used to find subgroups in the data with increased risk of EGWG based on their pre-pregnancy BMI and psychosocial risk factor scores at Time 1. FINDINGS: CART confirmed that self-reported BMI status was a strong predictor of EGWG risk for women who were overweight/obese pre-pregnancy. Normal weight women with low motivation to maintain a healthy diet and who reported lower levels of partner support were also at considerable risk of EGWG. IMPLICATIONS FOR PRACTICE: present findings offer support for inclusion of psychosocial measures (in addition to BMI) in early antenatal visits to detect risk of EGWG. However, these findings also underscore the need for further consideration of effect modifiers that place women at increased or decreased risk of EGWG. Proposed additional constructs are discussed to direct further theory-driven research. PMID- 26545493 TI - GroEL to DnaK chaperone network behind the stability modulation of sigma(32) at physiological temperature in Escherichia coli. AB - The stability of heat-shock transcription factor sigma(32) in Escherichia coli has long been known to be modulated only by its own transcribed chaperone DnaK. Very few reports suggest a role for another heat-shock chaperone, GroEL, for maintenance of cellular sigma(32) level. The present study demonstrates in vivo physical association between GroEL and sigma(32) in E. coli at physiological temperature. This study further reveals that neither DnaK nor GroEL singly can modulate sigma(32) stability in vivo; there is an ordered network between them, where GroEL acts upstream of DnaK. PMID- 26545494 TI - Roles of LIM kinases in central nervous system function and dysfunction. AB - LIM kinase 1 (LIMK1) and LIM kinase 2 (LIMK2) regulate actin dynamics by phosphorylating cofilin. In this review, we outline studies that have shown an involvement of LIMKs in neuronal function and we detail some of the pathways and molecular mechanisms involving LIMKs in neurodevelopment and synaptic plasticity. We also review the involvement of LIMKs in neuronal diseases and emphasize the differences in the regulation of LIMKs expression and mode of action. We finally present the existence of a cofilin-independent pathway also involved in neuronal function. A better understanding of the differences between both LIMKs and of the precise molecular mechanisms involved in their mode of action and regulation is now required to improve our understanding of the physiopathology of the neuronal diseases associated with LIMKs. PMID- 26545495 TI - Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy. AB - The number of B cells is increased and the O-glycans of IgA1 are incompletely galactosylated in IgA nephropathy (IgAN). Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN. Patients with IgAN exhibit higher miR-374b in B cells compared to controls. We show that miR-374b targets PTEN and Cosmc by luciferase assays and western blot analysis. Inhibition of miR-374b increased PTEN and Cosmc expression, and prevented cell proliferation and aberrant glycosylation of IgA1, thus representing a new therapeutic approach for IgAN. PMID- 26545496 TI - PKCbetaII inhibits the ubiquitination of beta-arrestin2 in an autophosphorylation dependent manner. AB - GPCR kinase 2 (GRK2)/beta-arrestins and protein kinase A (PKA)/protein kinase C (PKC) mediate homologous and heterologous regulations of GPCRs, respectively. Conventional protein kinase C enzymes (PKCs), as exemplified by PKCbetaII, selectively inhibit internalization of dopamine D2 receptor and beta2 adrenoceptor in a beta-arrestin- but not GRK2-dependent manner. PKCbetaII interacts with beta-arrestin2 upon autophosphorylation at T250, and inhibits the receptor internalization by decreasing the ubiquitination of beta-arrestin2. PKCbetaII interferes with the interaction between beta-arrestin2 and MDM2 in the cytosol, resulting in the redistribution of MDM2 to the nucleus. Subsequently, deubiquitination of beta-arrestin2 and inhibition of agonist-induced receptor internalization follow. Thus, our study suggests that the extent of beta-arrestin ubiquitination and the autophosphorylation status of PKCs determine PKCbetaII mediated inhibition of homologous regulatory processes of GPCRs. PMID- 26545497 TI - Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug resistance associated protein 6 (MRP6). AB - The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs. Two disease causing mutations changing the number of positive charges in the loops of TMD0 did not affect the membrane insertion efficiencies of the adjacent TMs. PMID- 26545498 TI - Exploiting Electrostatics To Generate Unsaturation: Oxidative Ge=E Bond Formation Using a Non pi-Donor Stabilized [R(L)Ge:](+) Cation. AB - The two-coordinate germanium cation [(IDipp){(Me3Si)2CH}Ge:](+) has been synthesized, which lacks pi-donor stabilization of the metal center and consequently has a very small HOMO-LUMO gap (187 kJ mol(-1)). It undergoes a variety of facile oxidative bond-forming reactions, most notably allowing access to the first examples of Group 14 metal cations containing M=E multiple bonds (E = C, N). The use of an electrostatic (rather than purely steric) strategy to discourage aggregation means that less bulky systems (for example, containing a primary alkylidene fragment, =CHR) are accessible. PMID- 26545499 TI - [TECHNICAL CHARACTERISTICS OF SPECIFIC FOOD PRODUCTS FOR PATIENTS WITH DYSPHAGIA]. AB - Dysphagia is a common problem among elderly and also in some pathological conditions such as neurodegenerative diseases or tumors. Making an adequate diet for this disease may present some difficulties. The aim of this document is to make a detailed technical report about the characteristics of the products that are available in Spain to hydrate and to feed patients with dysphagia. Food and pharmaceutical industries have developed a range of products designed to ensure homogeneous texture and a suitable viscosity to guaranty an adequate hydration. An adequate nutritional status is also achieved with these products for patients with dysphagia, without compromising their safety. The ingredients used to achieve a suitable viscosity are different types of starches, gums and other substances. It has been developed thickeners and gellified water for hydratation, and in case of food there are purees (dehydrated, lyophilized, pasteurized and sterilized), fruit purees, fruit pudding, and dehydrated cereal. Patients who do not meet their nutritional needs have also oral supplements with different viscosities. The industry offers extensive information about the technical characteristics of the products, except for viscosity. It would be recommended for the manufacturers to include in detail the technical specifications of the used methodology and the measurement and the results obtained in the analysis of viscosity that can be consulted by professionals of the Clinical Nutrition and Dietetics Units who treat these patients. PMID- 26545500 TI - [ENTERAL NUTRITION ON THE NUTRITIONAL STATUS OF CANCER]. AB - OBJECTIVE: to identify what effect causes enteral nutrition on nutritional status of cancer. METHOD: a search was performed using the keywords "Cancer" AND "Enteral Nutrition" AND "Supplementation" in four document databases: Pubmed, EBSCO, ProQuest, and Web of Science. INCLUSION CRITERIA: age of the sample, major than 18 years; submitted to surgery for cancer; that the intervention program was including diet and employment or not of nutritional Supplementation; clinical trials published between January 2004 and December 2014, in scientific journals indexed. RESULTS: we analyzed 660 articles, of which only 2% has been included. 58% of intervention programs are applied outside Spain; 84% of the interventions was carried out in a hospitable ambient; 58% of the sample is formed by adults older than 54 years; 33% of the interventions were multidisciplinary and its duration ranges between 1 and 4 years. DISCUSSION: we found just a few national interventions in cancer participants and there two types of interventions: by exclusive polymeric enteral formula or mixed with immunonutrition. CONCLUSIONS: enteral nutrition shows against the parenteral and its introduction at an early stage, it helps to improve nutritional status of the patient; polymeric formulas next immunonutrition, it helps to reduce the time of hospitalization; the analytical parameters are shown as a measurement pattern when assessing the improvement in nutritional status in cancer. It is recommended to increase the research in this field, especially in children. PMID- 26545501 TI - [EFFECTS OF GREEN TEA ON THE NUTRITIONAL STATUS OF THE EXERCISE]. AB - PURPOSES: assessing the magnitude of the effects of green tea in subjects that do exercise. METHODOLOGY: a search was been carried out with key words "green tea" AND "exercise" in four documentary databases: Pubmed, EBSCOHOST, OvidSP and Proquest. INCLUSION CRITERIA: adult age of the sample (18-65 years, based on WHO), and the consumption of a quantified amount of green tea or substitutes, along with doing physical exercise measurable in intensity, in clinical tests published between January 2010 and December 2014, whose source were indexed scientific journals. RESULTS: 260 articles were analyzed, of which 13 items were selected. 69% are studies with a designed workout, and 92% have included an exercise test to assess parameters. 77% fluctuate between 20-40 years and sample size between 9 and 36 subjects. 69% are long length. GTE has been the most used substitute (38%). 92% of studies have obtained some improvement and 92% of them, were significantly statistic. Interpretation of results: little homogeneity has been found in results in the analysis of results expression. Sample size is limited. There is a wide range of GTE substitutes and diversity of doses and exercise done. It cannot be possible to establish a dose, dosage and physical activity recommended. CONCLUSIONS: green tea gives us a wide variety of benefits in combination with physical exercise. There is a little evidence about quality. It cannot be possible to establish specific recommendations for obtaining benefits. PMID- 26545502 TI - [ANTIOXIDANT POTENTIAL OF MELIPONA BEECHEII HONEY AND ITS RELATIONSHIP TO HEALTH: A REVIEW]. AB - The present article provides a literature review about the biological potential of Melipona beecheii. The objective is to project some tendecies in research about nutraceutical aspects related to the bioactive compounds presents in the honey of this stingless bee species, known for its medicinal properties traditional, in the Yucatan Peninsula. Currently, there is strong evidence that M. beecheii honey has bioactive compounds such as proteins, flavonoids and polyphenols with high antioxidant activity. The scientific evidence allows to propose to the honey of stingless bee species as a potential alternative for the obtention of bioactive compounds with antioxidant activity in the Yucatan Peninsula and natural food being proposed to reduce some diseases associated with stress oxidative physiological human cells. However, there is still information that explains such antioxidant activity, therefore, according to the literature reviewed, sees the need to address nutraceuticals and functional aspects correlated with the bioactive compounds present in this honey bee. PMID- 26545503 TI - [GLUTAMINE AS AN AID IN THE RECOVERY OF MUSCLE STRENGTH: SYSTEMATIC REVIEW OF LITERATURE]. AB - BACKGROUND: after a traumatic injury or post surgical orthopedic, the loss of skeletal muscle strength is common. In addition to strength training schemes and/or resistance to treatment, it has been proposed as an additional treatment, the use of some amino acids such as glutamine (Gln) in isolation or combination with other nutrients. However, the information on the effectiveness of oral Gln supplementation during exercise strength schemes and / or endurance in adults with strength deficit is inconsistent. OBJECTIVE: to evaluate the strength of the evidence at hand about the effect of oral supplementation on muscle strength Gln set to strength training schemes and / or resistance in adult muscle strength deficit. METHODS: a systematic search was conducted in different databases, in clinical trials reported from the year 1980-2014, both in English and Spanish, about oral Gln supplementation alone or in combination with other nutrients, with a control group, in adults with strength deficits under exercise schemes of strength and / or endurance, tracking under a year and muscle power as the primary outcome. RESULTS: of 661 articles, six relevant studies were identified. The study participants in Gln isolation evaluation did not suggest changes between the groups, only an improvement in the perception of muscle weakness. Studies evaluating Gln with other nutrients, have reported results in favor of it. No meta-analysis was possible. CONCLUSIONS: nowadays there are insufficient data on the effects related to the Gln on the deficit of muscular force during exercise schemes in adults. It is required more research in this topic to respond more accurately about this fact. PMID- 26545504 TI - [THE VIBRATION TRAINING AS SARCOPENIA INTERVENTION: IMPACT ON THE NEUROMUSCULAR SYSTEM OF THE ELDERLY]. AB - INTRODUCTION: aging is accompanied by a progressive reduction of muscle mass that contributes to the development of functional limitations, and where vibration training may be an option for optimal intervention in the prevention and treatment of sarcopenia. OBJECTIVE: to assess the effectiveness of whole-body vibration in the neuromuscular system of the elderly. METHODS: systematic review in Medline, CINAHL, WOS and PEDro data by combining the descriptors of Medical Subject Headings concerning vibration training, muscle strength, muscle mass and older adults. RESULTS: a total of 214 studies were found on the vibration training in older people as either the only intervention or in combination with other exercises, of which 45 met the selection criteria. Of these, 30 items were eliminated by not more than 5 points according to the PEDro scale. They were included 15 clinical trials for final analysis. CONCLUSION: WBV training proves to be a safe, adequate and effective strength training method in the elderly population, but results are similar to conventional resistance exercise in the prevention and treatment of sarcopenia. PMID- 26545505 TI - BIOACTIVE SUBSTANCES WITH PREVENTIVE EFFECT IN CARDIOVASCULAR DISEASES. AB - The effect of diet on cardiovascular disease prevention has been widely studied for many years. Numerous studies have confirmed that diets rich in fruits and vegetables (Mediterranean diet) are beneficial to the cardiovascular system and various bioactive food components have preventive effect on chronic diseases such as cardiovascular disease. In this paper we review the effect of bioactive substances included in the group of flavonoids (catechins and proanthocyanidins, anthocyanins and isoflavones), stilbenes such as resveratrol, bioactive peptides, plant sterols and polyunsaturated fatty acids omega- 3 on the cardiovascular system. PMID- 26545506 TI - [BODY ADIPOSITY AND ITS RELATIONSHIP OF METABOLIC SYNDROME COMPONENTS IN COLOMBIAN ADULTS]. AB - OBJECTIVE: recently, Bergman et al. have introduced a new index of adiposity, namely, body adiposity index (BAI), as a marker of obesity excess body fat in clinical practice. We aimed to determine the prevalence of obesity and metabolic syndrome (MetS) and to assess the predicting ability of BAI in various atherogenic indices, MetS and its components among adult from Bogota, Colombia. METHODS: cross-sectional study in 690 male. MetS components (waist circumference >= 90 cm; fasting plasma glucose >= 100 mg/dL, blood pressure >= 135/85 mm Hg; triglycerides >= 150 mg/dL and HDL-c <= 40 mg/dL were measured. Atherogenic indices (cholesterol/HDL-c, LDL-c/HDL-c, triglycerides/HDL-c, lipid-metabolic index [LMI] and MetS score) were calculated. RESULTS: the prevalence of obesity by BAI (cut-point > 26.1%) and MetS was 50.1% and 19.1%, respectively. Subjects with MetS and obesity by BAI, show lower HDL-c levels and more frequently components of MetS (waist circumference, cholesterol and serum triglycerides). Predicting ability of BAI with a greater odds for atherogenic indices were 1.78 (95%CI 1.25 to 2.55), 1.46 (95%CI 1.01 to 2.14), 1.97 (95% 1.29 to 3.02), 2.04 (95%CI 1.23 to 3.39) and 1.47 (95%CI 1.03 to 2.11), elevation in LDL-c, LMI, MetS score and cholesterol/ HDL-c, and triglyceride/HDL-c, respectively (p < 0.05). CONCLUSION: subjects with higher levels of BAI show raised prevalence of obesity and positively associated with components of MetS. PMID- 26545507 TI - [PREVALENCE OF THINNESS, OVERWEIGHT AND OBESITY AMONG 4-TO-6-YEAR-OLD SPANISH SCHOOLCHILDREN IN 2013; SITUATION IN THE EUROPEAN CONTEXT]. AB - INTRODUCTION AND OBJECTIVES: both, weight excess and thinness, are related with several health disorders that could continue into adulthood. The objectives of this study were to estimate the prevalence of thinness, overweight and obesity in 4-to-6-year-old schoolchildren in the provinces of Cuenca and Ciudad Real (Spain), using both the International Obesity Task Force and the World Health Organization criteria; and to compare this prevalence with those provided for other European studies. METHODS: a cross-sectional study was performed in 1 585 schoolchildren in September 2013. Weight and height measurements were performed by previously trained nurses with standardized procedures. Weight status was defined according to the International Obesity Task Force and the World Health Organization criteria. RESULTS: when the International Obesity Task Force criteria were used prevalence of thinness, overweight and obesity was 20.51%, 11.84% and 8.58%, respectively; and 3.97%, 13.92% and 10.79% when the World Health Organization criteria were utilized. No statistically significant differences by sex or province in any category of weight status were found. The prevalence of thinness decreased as age increases. Conversely, thinness prevalence decreased and overweight/obesity prevalence was significantly higher in older schoolchildren. The prevalence of overweight in this study is similar to other Mediterranean countries. CONCLUSIONS: the prevalence of overweight seems to level off, although it remains a public health priority. The increase in the prevalence of thinness has become an emergent problem that could claim for public health interventions. PMID- 26545508 TI - [ANTHROPOMETRIC INDICATORS AND CARDIOMETABOLIC EVENTS AMONG SCHOOL-AGED CHILDREN FROM SONORA, MEXICO]. AB - INTRODUCTION: obesity in childhood is predictive of obesity in adulthood and it is associated with adverse health effect apparent since childhood; however, the joint assessment of obesity and adverse events among children in clinical settings is unusual. OBJECTIVES: to assess the association of overweight and obesity, abdominal obesity, and excess body fat with systolic [SBP] and diastolic [DBP] blood pressure, lipid profile and glucose levels; and to identify the best anthropometric indicator of such events. MATERIAL AND METHODS: we conducted a cross-sectional study in a sample of 412 schoolchildren. The presence of overweight and obesity, abdominal obesity and excess body fat was determined among all participants; levels of total cholesterol, triglycerides, high and low density lipoproteins, and glucose were measured in a subsample (n = 133). The associations of interest were assessed using adjusted linear and logistic regression models. RESULTS: 33% of the children were overweight or obese. Overall, overweight, obesity, abdominal obesity, and excess body fat were associated with elevated SBP and DBP and with a lipid profile and glucose levels that could indicate health risks among these children. Overweight and obesity were the best predictors of such events. CONCLUSIONS: among these school-aged children, we observed that obesity was associated with high odds of having adverse health outcomes such as high blood pressure, lipids and glucose. Such adverse events can be predicted by the presence of obesity measured by BMI, which is a noninvasive, inexpensive and easy to implement measure. PMID- 26545509 TI - SERUM CONCENTRATION OF NITRIC OXIDE IN WOMEN SMOKERS AND NONSMOKERS WITH OVERWEIGHT. AB - AIM: to evaluate the serum concentration of NO in overweight women, smokers (SG) and nonsmokers (NSG). METHODS: blood samples from smokers (n = 20) and nonsmokers (n = 18) were collected to obtain serum, and stored at -80 degrees C until analysis. NO was assessed by measuring total nitrite, determined by Greiss method. It was adopted as reference 24.4 MUmol/L, mean value found in a study with healthy subjects without excess weight. We used the Student t test to compare the means of age and waist circumference, and the Mann-Whitney U test to compare the median of concentrations of nitrite, number of cigarettes/day and Body Mass Index. We adopted a significance level of p < 0.05. RESULTS: the median nitrite in SG was 16.53 (2.79 - 69.72) MUmol/L, whereas in NSG was 10.85 (1.44 - 43.25) MUmol/L (p = 0.028). BMI median value to SG and NSG, was respectively 29.50 (25.00 - 38.14) kg/m2 and 30.68 (25.10 - 36.98) kg/m2 (p = 0.530), being classified as overweight. The data showing that the average nitrite was below the estimated value for healthy individuals. CONCLUSION: the results indicate a decrease of NO metabolites in women with excess weight, independently of being smoker. Despite the significant difference found between groups, these women had values well below the reference value of NO for healthy women. Therefore, it seems that smoking does not interfere in nitrite levels in patients already compromised by obesity. PMID- 26545510 TI - ASSOCIATIONS BETWEEN ENERGY AND FAT INTAKES WITH ADIPOSITY IN SCHOOLCHILDREN - THE CUENCA STUDY. AB - INTRODUCTION: the relationship between changes in energy intake (EI) over the last few decades and the trends towards of excess weight in children is still debated. OBJECTIVE: to examine the relationship between energy and macronutrient intakes with adipostity in children, controlling for cardiorespiratory fitness (CRF) as a surrogate measure of physical activity. METHOD: we conducted a cross sectional study of 320 schoolchildren aged 9-11 years (54.5% girls). We collected data on socio-demographic variables, and measured weight, height, waist circumference (WC), and fat mass percentage by bioimpedance analysis. Fat mass index (FMI) was calculated as fat mass (kg) divided by height (m) squared, to adjust for body size. Energy (kcal) and macronutrient intake (percentages) were measured by two non-consecutive 24-h recalls (weekday and weekend day), using the Young Adolescents' Nutrition Assessment on Computer (YANA-C) software program; CRF was measured by the 20-m shuttle run test. RESULTS: boys in the 4th quartile of the WC distribution had lower fat intake (34.9%) than boys in the 1st (42.4%; p = 0.019) and 2nd quartiles (41.6%; p = 0.022). Children in the 1st quartile of the FMI distribution had higher daily EIs than children in the 4th quartile (1762.3 kcal vs. 1496.8 kcal; p = 0.023). All macronutrient intakes relative to weight were lower in children in the more adipose categories for weight status, WC and FMI (p < 0.001). CONCLUSION: adiposity was inversely related to energy and fat intakes. Excessive EI and high EI from fats not appears to be directly associated with the current obesity epidemic among schoolchildren living in Cuenca (Spain). PMID- 26545511 TI - [PSYCHOMETRIC PROPERTIES OF A SPANISH ADAPTATION OF THE WEIGHT BIAS INTERNALIZATION SCALE (WBIS)]. AB - INTRODUCTION: obesity is currently one of the most important international health problems, and the study of the various aspects related to it has become a priority. One such aspect is the analysis of the weight bias internalization, especially its evaluation, for which different instruments hare been designed, though they are not available for Spanish population. OBJECTIVES: the objective of this study is the translation and adaptation of the Weight Bias Internalization Scale (WBIS), analyzing its psychometric characteristics. METHODOLOGY: fifty-nine people were evaluated by a Spanish adaptation of WBIS, the Beck Depression Inventory (BDI) in short version, and the General Health Questionnaire Goldberg (GHQ-28). Internal consistency was explored, as well as concurrent and construct validity of the adapted instrument. RESULTS: Cronbach's alpha coefficient was .89, while the concurrent validity showed statistically significant correlations with the total score of GHQ-28 (r = .39, p < .02) and the BDI (r = .42, p < .001). The final scale consists of 11 items, which are grouped into two main factors, and allow a significant explanation of 65.03% of the variance. CONCLUSIONS: the Spanish adaptation of the WBIS shows good psychometric values of reliability and validity, so it might be a good scale for the assessment of the weight bias internalization, which could be confirmed in larger studies. PMID- 26545512 TI - GLUTATHIONE PEROXIDASE-1 PRO200LEU POLYMORPHISM (RS1050450) IS ASSOCIATED WITH MORBID OBESITY INDEPENDENTLY OF THE PRESENCE OF PREDIABETES OR DIABETES IN WOMEN FROM CENTRAL MEXICO. AB - INTRODUCTION: obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. OBJECTIVE: to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. METHODS: 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. RESULTS: for rs10504050 polymorphism there were differences (Xi2 = 6; p = 0.01) between frequency (0.61) of obese carriers (Pro/Leu plus Leu/Leu) and CG carriers (0.42), and between (Xi2 = 8; p = 0.004) morbid (IMC > 40) obesity (0.74) and CG carriers. The obese group (OB) showed a prevalence of 66% of prediabetes plus diabetes. There were no differences in frequencies of rs10504050 in OB with pre or diabetes versus CG, or versus obese participants without diabetes. TBARS concentration was greater in all the degrees of OB versus CG. CONCLUSION: GPx-1 Pro200Leu polymorphism was associated with obesity especially with morbid obesity, but not with obese participants with prediabetes or diabetes. Oxidative stress is present in all grades of obesity significantly. PMID- 26545513 TI - [OBESITY MANAGEMENT IN THE PRIMARY CARE SETTING BY AN INTENSIVE LIFESTYLE INTERVENTION]. AB - OBJECTIVE: the aim of this study was to compare an Intensive Lifestyle Intervention against Traditional Treatment for obesity management in the primary care setting. SUBJECTS AND METHODS: interventional randomized controlled study with participation of 42 obese adults. Subjects assigned to the Intensive Lifestyle Intervention received a validated behavior change protocol "Group Lifestyle Balance" in 12 sessions, weekly consultations by a nutritionist and meal replacements. Traditional Treatment consisted of monthly consultations with a nutritionist that provided nutritional assessment and physical activity. RESULTS: almost all study participants (97%) were measured after 3 months of intervention. Intensive Lifestyle Intervention and Traditional Treatment subjects showed the following changes in body weight: (Median [25-75th percentile]) (-4.7 kg [-6.5, -3.1]) vs. (+0.4 kg [-0.3, 1.3]). Sixty two percent of Intensive Lifestyle Intervention group participants lost more than 5 % body weight vs. 0 % in the traditional treatment group (p < 0.001). CONCLUSIONS: this preliminary evidence showed that an Intensive Lifestyle Intervention can be an effective strategy for obesity management in the primary care setting. PMID- 26545514 TI - DETERMINATION OF CHOLESTEROL IN HUMAN MILK: AN ALTERNATIVE TO CHROMATOGRAPHIC METHODS. AB - INTRODUCTION: human milk (HM) is considered the best option for feeding healthy infants. Cholesterol (CHOL) is important for proper development of the nervous system, and for hormone and vitamin synthesis in growing infants. Breastfeeding and dietary CHOL intake during infancy have been suggested to affect blood lipid levels and the risk of cardiovascular disease in adulthood. Gas chromatography is the technique most widely used to determine CHOL in HM. Chromatographic methods are specific for the determination of CHOL and other sterols present in HM, but are extremely time consuming, and the costs and equipment requirements mean that they are not accessible to all laboratories. AIM: the present study describes the optimization and validation of an enzymatic-spectrophotometric method for CHOL determination in mature HM. METHOD: determination of CHOL involves fat extraction with chloroform:methanol, hot saponification and extraction of the unsaponifiable fraction with diethyl ether. CHOL was determined by an enzymatic method in which the concentration of the lutidine dye formed is stoichiometric to the amount of CHOL, and is measured by the increase in light absorbance at 405 nm. RESULTS: human milk fat (mg/mL) (27.5 +/- 1.3) and CHOL (0.113 +/- 0.004) in analyzed HM were within the ranges reported by others authors. Analytical parameters of the proposed method were assessed: The precision values (%) (expressed as the relative standard deviation (RSD)) were: 3.5 and 6.7 for intra- and inter-day, respectively. Accuracy, estimated by recovery assays, was 110 +/- 1.6%. CONCLUSION: the validated enzymatic-spectrophotometric method for determining CHOL in HM constitutes an alternative for fast and simple analysis of CHOL with equipment requirements accessible to any laboratory. PMID- 26545515 TI - [SOCIODEMOGRAPHIC AND HEALTH CHARACTERISTICS ASSOCIATED WITH LOW BIRTH WEIGHT IN THE CANARY ISLANDS]. AB - INTRODUCTION AND OBJECTIVE: since 1976, the term low birth weight (LBW) has been applied to all infants weighing less than 2 500 g and it constitutes the most important factor affecting neonatal mortality, morbidity in childhood. The aim of this study is to identify associations between biological, socioeconomic and health factors and underweight newborns in the Canary Islands. MATERIALS AND METHODS: a cross-sectional epidemiological study was conducted, with the files belonging to pregnant women in 2011 and 2012 (n = 11.768) at the Hospital Universitario Insular Materno of Gran Canaria, which accounted for 66.3% of all births in the province for those years, excluding from the analysis the data pertaining to multiple births (393) (3.3%). The distribution and frequency of weight by sociodemographic characteristic were analyzed. Percentages were compared using the chi2 test, means with the t-test and medians with the Wilcoxon test for independent data. Those variables that were associated with low birth weight in the univariate analysis were entered into a logistic multidimensional analysis. RESULTS: the distribution of birth weight revealed an of excess underweight children (9.3%), of which (62.1%) were pretermature. Mothers of children with LBW are thinner, of a smaller size and BMI (< 18.5 kg/m2), and an average age of 31.5. It was also noted that there is an increase between the age of the mothers and low weight although the effect is not linear; in fact, the increases in the risk of LBW accelerate as age increases. When maternal BMI decreases, to approximately below 25, the risk of low birth weight increases linearly. The highest OR correspond to fetal intrauterine growth retardation (CIR) (OR = 6.3; 95% CI = 5.3, 7.4), hypertension/eclampsia (OR = 3.2; 95% CI = 2.1; 5.1), in gestations of less than 37 weeks (OR = 2.5; 95% CI = 2.0; 3.3) and the consumption of tobacco by the mother (OR = 1.9; 95% CI = 1.6, 2.3). CONCLUSIONS: smoking during pregnancy appears to be the most important mediating factor in IUGR mediating factor. An overweight or obese mother did not appear to constitute a risk factor for a child's low birth weight. Intrauterine growth restriction (IGR) is the variable health that most affects low weight and high blood pressure in the mother, also associated with fetal growth retardation. While it is true that lack of antenatal care cannot be considered as a causal factor of underweight babies, 47.1% of pregnant women in the Canaries had insufficient controls (< 3 controls) with an increase of said controls would make it possible to reduce the frequency of the low weight in newborns. PMID- 26545516 TI - CHANGES IN C-REACTIVE PROTEIN AND BIOCHEMICAL PROFILE IN PRESCHOOL CHILDREN WITH OBESITY. AB - INTRODUCTION: the childhood obesity is a serious public health problem because if weight gain continues, complications such as insulin resistance, dyslipidemia, orthopedic disorders, sleep apnea, and metabolic syndrome may occur in other stages of child development. OBJECTIVE: the objective of this study was to evaluate C-reactive protein (CRP) concentrations, lipid profiles, and glucose levels in obese children three to five years of age and compare them to eutrophic children. METHODS: in this study, 100 children aged three to five years were selected and divided into two groups (n = 50 per group): a group of eutrophic children (< 84th percentile) and a group of obese children (> 95th percentile). An anthropometric evaluation and quantification of plasma levels of ultrasensitive CRP, triglycerides, cholesterol, LDL-C, HDL-C, and glucose were performed. RESULTS: the data showed a significant increase in obese children with regard to height (p < 0.005), weight (p < 0.0001), body mass index (p < 0.0001), ultrasensitive CRP (p < 0.0001), triglycerides (p < 0.0001), LDL (p < 0.0001), and glucose levels (p < 0.0001) as well as decreased levels of HDL (p < 0.0001) compared to eutrophic children. CONCLUSIONS: metabolic changes that occur in obese preschool children are characterized by increases in inflammatory markers and lipid profiles. Considering that during preschool age the programming and number of adipocytes that will remain with the individual for the rest of their life are determined, this stage is crucial in the development of complications associated with obesity. PMID- 26545517 TI - BEHAVIOR OF ADIPOKINES AFTER A YEAR FOLLOW-UP IN THE OBESITY OUTPATIENT CLINIC FOR CHILDREN AND ADOLESCENTS. AB - OBJECTIVE: demonstrate adipokines progression, along 12 months, in obese children and adolescents who attend the Obesity Outpatient Clinic for Children and Adolescents of the HCPA. METHODS: children and adolescents in medical treatment for obesity were followed for 12 months, assessing anthropometry, blood pressure, waist circumference, lipid profile, fasting blood sugar and insulin, inter leukine- 6, tumor necrosis factor alpha, and adiponectin in two points in time: at inclusion and after 12 months follow-up in the Obesity Outpatient Clinic for Children and Adolescents. RESULTS: 27 children and adolescents were assessed with median age of 10.3 years. The mean BMI z-scores lowered during this period (p < 0.01), HDL-c increased in the period (p = 0.025). The medians of adipokines did not vary during the period: IL-6 (p = 0.470), TNF-alpha (p = 0.753) and adiponectin (p = 0.943). There was no correlation of IL-6 and TNF-alpha with central and global obesity along the 12-months follow-up. Adiponectin increased in 45% of the sample, the increase being more pronounced in females. CONCLUSION: children and adolescents in medical treatment for obesity, after one-year follow up, did not improve their adiponectin profile. PMID- 26545518 TI - [ASSOCIATION BETWEEN MUSCULAR FITNESS AND PHYSICAL HEALTH STATUS AMONG CHILDREN AND ADOLESCENTS FROM BOGOTA, COLOMBIA]. AB - OBJECTIVE: epidemiological and experimental evidence suggest the role of muscular strength has been increasingly recognized in the prevention of chronic disease in early life, and features of the cardiometabolic disease have also been negatively associated with muscle strength in adulthood. The aim of this study was to examine whether the association between muscular fitness and physical health status among children and adolescents from Bogota, Colombia. METHODS: cross sectional study in 921 schoolchildren aged 8-11 years from Bogota, Colombia. A muscular fitness score (MFS) was measured using handgrip strength and standing long jump and vertical jump. Each of these variables was standardized as follows: standardized value = (value = mean)/SD. The muscle fitness score was calculated as the mean of the three standardized scores. MFS was recoded into quartiles Q1 (low fitness) to Q4 (high fitness). The body mass index (BMI), skinfold thickness, waist and hip circumference, body composition by bioimpedance (BIA), blood pressure and self-declaration sexual maturation were measured such as indicators associated with future cardiovascular events. RESULTS: the average age was 13.0 +/- 2.6 years. Participants with Q4 (high fitness), show a better physical health status (BMI, blood pressure, body fat and waist circumference (BMI, blood pressure, body fat and waist circumference, p[linear X2] = 0.01). Individuals with Q1 and Q3 (low fitness) had 4.06 times (95%CI 2.60 to 6.34; p = 0.043) risk of excess body fat and 1.57 times (95%CI 1.02 -1.89; p = 0.020) risk of abdominal obesity. CONCLUSION: our results show that muscle fitness is associated with better physical health status. The testing of muscle strength at early ages should be included in health- monitoring systems. PMID- 26545519 TI - [RELATIONSHIP BETWEEN PATTERNS OF BREASTFEEDING AND BLOOD PRESSURE IN BRAZILIAN AND SPANISH SCHOOLCHILDREN]. AB - INTRODUCTION: the relationship between early feeding and blood pressure in later life is still uncertain and sometimes contradictory. Some studies point to the protective effect of breastfeeding on cardiovascular disease, while others do not obtain conclusive results. OBJECTIVES: the aim of this study was to analyze the relationship between breastfeeding patterns during the first months of life and blood pressure in childhood, in two samples of children from two populations with different socio-cultural characteristics, controlling for quality feeding in infancy. METHODS: the study, with a transversal and retrospective design, was conducted with 492 schoolchildren aged between 8 and 10 years, it consists of two samples, both collected from public schools, one in Madrid (Spain) and one in Vitoria, Espirito Santo (Brazil). RESULTS: ninety percent of the sample was breastfed, 196 (44.2%) from Madrid and 247 (55.7%) from Vitoria/ES. The average duration of exclusive breastfeeding (EBF) in Madrid was 12.89 weeks (std = 9.6) and in Vitoria/ES, 22.00 weeks (std = 13.4), with statistically significant differences. The mean values of systolic and dyastolic blood pressure, were significantly higher in the Brazilian sample. The prevalences of borderline hypertension and hypertension were also higher in Brazil than in Spanish, 68% vs 32% and 60% vs 40%, respectively. Association between shorter duration of EBF and higher prevalence of hypertension in childhood, was observed in the two samples. Regarding the association between diet quality and blood pressure values, this was only significant in the Brazilian sample, but not in Spanish. DISCUSSION: in both samples a protective effect of breastfeeding on blood pressure was observed, however when comparing the two samples appear to be a contradiction since the Brazilian children were breastfed for longer than the Spaniards but their Pressure Arterial values and the Hypertension prevalence were higher in the Spanish sample. This contradiction is resolved by controlling the effect of feeding in infancy. The food quality of Brazilian children is worse than that of Spaniards, mainly due to a higher consumption of processed foods very high in sodium content. CONCLUSION: the possible protective effect of breastfeeding, is reduced at later stages of the life cycle if food habit are not appropriate or do not meet minimum quality requirements. Therefore, although breastfeeding plays an important role in preventing the development of hypertension in children is not enough to support the practice of breastfeeding but prevention work is ongoing and should insist on eating habits and promote healthy lifestyles throughout the entire life cycle of people. PMID- 26545520 TI - MOTOR SKILLS AND NUTRITIONAL STATUS OUTCOMES FROM A PHYSICAL ACTIVITY INTERVENTION IN SHORT BREAKS ON PRESCHOOL CHILDREN CONDUCTED BY THEIR EDUCATORS: A PILOT STUDY. AB - INTRODUCTION: childhood obesity is a worldwide health concern. For this issue different intervention have being planned to increase physical activity patterns and reduce the excess of weight in children with limited or no success. OBJECTIVE: the aim of this study is to evaluate the results of a pilot intervention consisting in three 15-minute breaks conducted by educators and supervised by physical education teachers on motor skills and nutritional status in preschool children. METHODS: sample was 70 preschool children (32 boys and 38 girls), age 4 +/- 0,6 years. The physical activity classes were performed three times a week, 45 minutes daily, distributed in three 15 minutes breaks. The circuits were planned to have; jumps, sprints, carrying medicinal balls, gallops and crawling. Motor skill tests that were performed Standing long jump (SLJ) and Twelve meter run. RESULTS: with the intervention no significant differences in nutritional status where found on mean Z score (boys p = 0.49, girls p = 0.77). An increment on weight and height was fount after the intervention (p < 0.0001). Regarding the 12 meter run test, we found significant changes after the intervention when we normalize by weight in boys (p = 0.002) and girls (p < 0.0001). Our results have shown than boys significantly increased their SLJ and SLJ normalized by weight (p < 0.0001); a similar result was found in girls after the intervention (p < 0.0001) suggesting the increment of power independent of weight gain. CONCLUSIONS: in conclusion, this pilot study found that an intervention with more intense activities in small breaks (15 minutes), and guided by the educators could improve essential motor skills (running and jumping) in preschool children of a semi-rural sector independent of nutritional status. This gaining in motor skills is the first step to increase physical activity levels in preschool children. PMID- 26545521 TI - EVALUATION OF THE EFFECTS OF A PROGRAMME PROMOTING ADEQUATE AND HEALTHY EATING ON ADOLESCENT HEALTH MARKERS: AN INTERVENTIONAL STUDY. AB - AIM: to evaluate the effects of a protocol promoting adequate and healthy eating on adolescent health parameters. METHODS: this controlled intervention study was conducted for 9 months, with the participation of adolescents enrolled in two schools (intervention/control) located in a poor neighbourhood in the city of Salvador (Bahia), Brazil. For the intervention school, activities promoting adequate and healthy eating were designed based on the Food Guide for the Brazilian Population (Guia Alimentar para a Populacao Brasileira). Students underwent biochemical, sexual maturation and anthropometric tests at baseline and at the end of the 9-month period. In addition, students answered a questionnaire on food consumption, physical activity and sedentary behaviour. Information on the socioeconomic status of their family was also obtained. Generalized Estimating Equation (GEE) analysis was chosen to evaluate the associations of interest. RESULTS: students under intervention presented decreases of 7.64 mg/dL in mean total cholesterol (TC) (p = 0.009) and 7.77 mg/dL in mean low-density lipoprotein cholesterol (LDLc) (p = 0.003) and increases of 18% in legume consumption (odds ratio [OR] = 1.18; 95% confidence interval [CI] 1.03-1.37) and 17% in vegetable consumption (OR = 1.17; 95%CI 1.01-1.35) compared with students who did not undergo intervention. No differences were observed in the anthropometric parameters analysed. CONCLUSION: the results showed a positive effect of activities promoting adequate and healthy eating on reducing TC and LDLc and on increasing the consumption of vegetables and legumes, evidencing that the intervention model was able to prevent and/or treat cardiovascular risk factors in adolescents. PMID- 26545522 TI - CORRELATION OF SERUM VITAMIN D LEVEL WITH TYPE 1 DIABETES MELLITUS IN CHILDREN: A META-ANALYSIS. AB - OBJECTIVE: to assess the relationship between serums vitamin D level and type 1 diabetes mellitus (T1DM) in children. METHODS: the following electronic databases were searched until Sep 2014 to identify relevant studies that assessed the relationship between serum vitamin D with T1DM: PubMed?EMbase?Medline?Central Register of Controlled Trials?CBM?Chinese National Knowledge Infrastructure (CNKI)?wangfang; The NOS scale was used to evaluate the quality of studies, and the statistical tests were performed by Stata 11.0 software. RESULT: a total of 10 studies were included in this study. Our results showed that serum vitamin D was significantly lower in children with T1DM than in healthy controls (MD = 0.60, P < 0.05). No evidence support publication bias in present study. CONCLUSION: the meta-analysis suggests that serum vitamin D level is associated with T1DM in children. PMID- 26545523 TI - NORMATIVE VALUES OF EQ-5D-5L FOR DIABETES PATIENTS FROM SPAIN. AB - INTRODUCTION: diabetes is a metabolic disease that can lead a reduction in health related quality of life. The EQ-5D is a generic preference-based health-related quality of life questionnaire widely used in patients with diabetes. OBJECTIVE: the aim of the current manuscript is to provide normative values of EQ-5D-5L for Spanish people suffering from diabetes. METHODS: data from the Spanish Health Survey (2011/2012) was utilized. A total of 1 857 people suffering from diabetes participated in the survey. EQ-5D-5L scores were defined by sex, region (including the 17 Autonomous regions and 2 Autonomous cities of Spain), and 8 age groups. RESULTS: mean EQ-5D-5L utility index for the whole sample was 0.742. It was better for men (0.826) than for women (0.673). Similar results were observed in the VAS. The ceiling effect was much higher for men (44.83%) than for women (24.41%). CONCLUSIONS: the current study provides EQ-5D-5L normative and representative data for Spanish people suffering from diabetes. PMID- 26545524 TI - OVERWEIGHT OBESITY AND CARDIOVASCULAR RISK IN MENOPAUSAL TRANSITION. AB - INTRODUCTION: the hormonal decline that is characteristic of the menopause, in conjunction with the associated weight gain, is considered a determinant factor of cardiovascular risk. OBJETIVE: to examine weight status in relation to clinical symptoms during the menopausal transition, in women referred from primary care to an endocrinology specialist, to determine potential cardiovascular risk profiles. METHOD: observational analytic cross-sectional study, conducted with data from medical records created at time of referral. STUDY POPULATION: 805 women aged 40 years or older, a sufficient number of subjects and medical records for cardiovascular risk to be estimated. RESULTS: hierarchic cluster analysis distinguished four clusters. The prevalence of obesity in each one exceeded 60%. The highest mean cardiovascular risk was observed in women who were older and presented obesity and hypertension. In younger age groups, the risk was low, rising to levels similar to those of the older women by the age of 65 years. CONCLUSION: these results suggest that preventive and therapeutic monitoring of obesity and modifiable risk factors should be conducted during the menopausal transition, to reduce the risk attributable to these factors, a risk that increases with time. PMID- 26545525 TI - APPLICATILITY OF THE VISCERAL ADIPOSITY INDEX (VAI) IN THE PREDICTION OF THE COMPONENTS OF THE METABOLIC SYNDROME IN ELDERLY. AB - The nutritional assessment may detect a state of malnutrition, overweight and cardiometabolic risk in the elderly. Easy to apply instruments enable the identification of risk factors for cardiovascular diseases (CVD). OBJECTIVE: to analyze the applicability of Visceral Adiposity Index (VAI) in the prediction of MS components in the elderly. METHODS: cross-sectional study with 221 elderly at a mean age of 70.65 +/- 7.34 years; 53.4% female and 46.4% male. Weight, height, waist circumference (WC), fasting glucose, triglycerides (TG), total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and blood pressure (BP), data was obtained, as well as information about lifestyle. There were calculated the Body Mass Index (BMI), the Waist-Hip Ratio (WHR), and the VAI. The adiposity measures were compared with the components of MS, and for the VAI there was determined the capability of predicting the occurrence of MS components. RESULTS: by analyzing the association among the biochemical and pressoric variables and MS components with the anthropometric indicators of obesity, there was a direct and significant correlation of the BMI, the weight and the VAI with blood glucose, HDL and TG (p. PMID- 26545526 TI - ACCEPTANCE OF FUNCTIONAL FOOD AMONG CHILEAN CONSUMERS: APPLE LEATHER. AB - AIM: the aim of this study is to measure acceptance of a specific functional food: apple (fruit) leather, based on organoleptic characteristics and to identify consumer types and preferences for natural additives which increase the product's functionality and meet current nutritional needs. MATERIALS AND METHODS: a sample of 800 consumers provided an evaluation of apple leather in terms of acceptance (liking). A sensorial panel was carried out using a 9-point hedonic scale. Cluster analysis was used to identify different acceptance-based consumer types. In addition, a conjoint analysis was carried out to determine preference for different additives. RESULTS: the cluster analysis resulted in four groups with significant differences in the average likings obtained from the sensory panel. Results indicate that the sweetness of the tested apple leather was evaluated best among all groups and, on average, color was rated as the worst attribute. However, overall likings differ significantly between groups. Results from the conjoint analysis indicate that, in general, consumers prefer natural additives included in the product which enhance functionality. CONCLUSIONS: although there is a "global acceptance" of the product, there are significant differences between groups. The results of the conjoint analysis indicate that, in general, consumers prefer the aggregation of natural additives which increase the product's functionality. Apple leather with natural additives, such as anticariogenics and antioxidants, can be considered a functional substitute of unhealthy snacks and/or sweets. PMID- 26545527 TI - [SNACK HIGH WHEY PROTEIN IMPROVES THE LEVEL OF SATIETY AND REDUCES APPETITE HEALTHY WOMEN]. AB - BACKGROUND: the nutritional content and energy density of foods is related to greater control of appetite, satiety and reducing food intake. METHODS/SUBJECTS: the randomized crossover study included 20 healthy women, aged 20 and 30 years with a BMI of 20 to 24.9 kg/m2 and who completed that included 3 day trial comparing 8 hours 130 kcal snacks consumed afternoon: yoghurt with added whey protein (PSL), biscuits and chocolate. Participants consumed a standardized menu; snack was consumed 3 hours after lunch. Perceived hunger and fullness were evaluated during the afternoon until dinner voluntary intake ad libitum. They repeat the same snack 3 times. RESULTS: consumption of yogurt with PSL led to a further reduction of appetite in the afternoon in front of the snack of chocolate and biscuits (p < 0.001). No differences of appetite in the afternoon between chocolate vs cookies but significant difference between yogurt with PSL and other treatments (p < 0.001) were detected. At snack, yogurt there was a significant reduction in caloric intake compared to other snacks (p < 0.001) and a later request for dinner with about 45 minutes apart. CONCLUSIONS: snacks with less energy density and rich in protein (yogurt with PSL) improve the control of appetite, satiety and reduces food intake in healthy women later. PMID- 26545528 TI - [VITAMIN D AND CHRONIC LUNG COLONIZATION IN PEDIATRIC AND YOUNG ADULTS CYSTIC FIBROSIS PATIENTS]. AB - INTRODUCTION AND OBJECTIVES: evaluate vitamin D status and its association with chronic lung colonisation in Cystic Fibrosis patients. MATERIAL AND METHODS: descriptive cross-sectional multicenter study. From November 2012 to April 2014, at 12 national hospitals, 377 patients with Cystic Fibrosis were included. Vitamin D levels < 30 ng/ml were classified as insufficient. Chronic colonisation was considered if they had at least two positive cultures in the past year. RESULTS: the median age was 8.9 years (2 months to 20 years). 65% had insufficient levels of vitamin D. There was an inverse correlation between age and vitamin D levels (r = -0.20 p < 0.001). Those diagnosed by screening, were younger and had higher levels of vitamin D. There was an inverse correlation between the number of colonisations and vitamin D levels (r = -0.16 p = 0.0015). Adjusting for age, pancreatic status and diagnosis by screening, colonization by S. aureus in 6 years, increased the risk of insufficient levels of vitamin D: OR 3.17 (95% CI 1.32 to 7.61) (p = 0.010) and OR 3.77 (95% CI 1.37 to 10 , 37) (p = 0.010), respectively. CONCLUSIONS: despite adequate supplementation, more than half of our patients did not achieve optimal levels of vitamin D. Regardless of age, diagnosis by screening or pancreatic status, chronic colonization by Pseudomonas sp. in children and adolescents and S. Aureus in infants and preschoolars increases the risk of developing vitamin D deficiency in these patients. PMID- 26545529 TI - THE EFFECT OF DIETARY WHEAT BRAN ON SUCROSE-INDUCED CHANGES OF SERUM GLUCOSE AND LIPIDS IN RATS. AB - INTRODUCTION: wheat bran has been known for many health benefits, but its glucose and lipid-lowering activity still remains unresolved. OBJECTIVE: to investigate effects of varying amounts of wheat bran and feeding period on serum glucose and lipids in sucrose-fed rats. METHODS: eighty male Sprague-Dawley rats were assigned into 4 sucrose-based diets containing either 0, 5, 10 or 20% wheat bran (WB) and given ad libitum to rats for 4, 8, 12 or 16 weeks. Serum glucose, total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C and HDL C), triglycerides (TG), phospholipids (PL) and total lipids (TL) were quantified at end of each feeding period and other biological parameters were assessed. RESULTS: in all feeding periods, food intake showed ascending linear trend (p < 0.05), whereas body weight did not respond to WB. Compared to 0%, 10 or 20% WB induced decrease (p < 0.05) in TC (16 weeks) and HDL-C (12 or 16 weeks), whereas 5, 10 or 20% WB induced similar decrease in PL (4 or 12 weeks), TL (all periods) and glucose (4 or 8 weeks). This glucose- and lipid- lowering effect was substantiated by descending linear responses (p < 0.05) to WB. PL and TL descending responses to WB were seen in all feeding periods. TG exhibited no change with WB, but linearly responded (4 or 8 weeks). Differences in glucose or lipid variables of rats fed WB diets for all feeding periods were less evident. CONCLUSIONS: results suggest that wheat bran reduces serum glucose and lipids mainly phospholipids in sucrose fed rats in an interaction that is likely to have clinical implications in cardiometabolic conditions. PMID- 26545530 TI - [IN VIVO EFFECT OF RED WINE UNDILUTED, DILUTED (75%) AND ALCOHOL-FREE ON THE GENOTOXIC DAMAGE INDUCED BY POTENTIAL CARCINOGENIC METALS: CHROMIUM [VI]]. AB - INTRODUCTION: the carcinogenesis may be initiated and promoted by the oxidative DNA damage. The compounds of chrome (Cr [VI]) cause oxidative stress (EOx) and are recognized as carcinogens in humans. In this sense, it is proposed that drinks with a high antioxidative potential, such as red wine, may have protective or modulatory effects on the oxidative DNA damage. OBJECTIVE: to study the effects of the administration in vivo of undiluted, diluted (75%) and alcohol free red wine on the genotoxic damage induced by carcinogenic metals (Cr [VI]), by evaluating the micronucleus (MN) in polychromatic erythrocytes (EPC) in mice (CD-1). MATERIAL AND METHOD: it was randomly organized the follow groups: (i) control, (ii) undiluted, diluted and alcohol-free red wine (free access), (iii) CrO3 (20 mg/kg by intraperitoneal route) and (iv) CrO3-red wine. The evaluations were made in blood samples obtained from the caudal vein, in which it was identified the MN and EPC before, during and after treatments. RESULTS AND DISCUSSION: the red wine (diluted and alcohol-free) was capable of decreasing the averages of MN induced by CrO3, demonstrating its modular capacity in vivo in the oxidative DNA damage caused by EOx-induced carcinogens. The administration of only undiluted red wine presented toxic effects. CONCLUSIONS: our results raises expectations on the use of substances like the red wine for the protection or modulation of genotoxic damage, encouraging its application in the carcinogenic and mutagenic processes. PMID- 26545531 TI - MATERNAL AND POST-WEANING EXPOSURE TO A HIGH FAT DIET PROMOTES VISCERAL OBESITY AND HEPATIC STEATOSIS IN ADULT RATS. AB - AIM: considering the frequent consumption of fat-rich diets by women of reproductive age, the aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during the perinatal and/ or post-weaning period on the liver parameters and lipid metabolism of young rats. METHODS: Wistar female rats were fed a high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated to four groups: Control Control (CC, n = 11), offspring fed a control diet after weaning; Control High-fat (CH, n = 10), offspring fed a high-fat diet after weaning; High-fat High-fat (HH, n = 10), offspring of mothers H fed a high-fat diet after weaning; and High-fat Control (HC, n = 9), offspring of mothers H fed with control diet after weaning. RESULTS AND DISCUSSION: the food intake did not differ among the groups, however, the relative weight of the adipose tissue was higher in animals from the HC, HH and CH groups (p <= 0.005). Liver steatosis was found in the CH and HH animals, which also exhibited hypercholesterolemia (p <= 0.05). The levels of the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) were higher in the HH group, and the LDL level was higher in the CH group compared to the CC. The consumption of an obesogenic diet during critical periods of development may contribute to the occurrence of visceral obesity, liver steatosis and hypercholesterolemia in adult rats, even in the absence of changes in dietary intake. PMID- 26545532 TI - FACTORS RELATED TO TOTAL ENERGY EXPENDITURE IN OLDER ADULTS (CHILE). AB - AIM: to asses Total Energy Expenditure (TEE) in healthy Chilean institutionalized or independently older people Methods: twenty seven young (27-30 years), 27 institutionalized (> 65 years old) and 27 free-living older (> 65 years old) participants were studied. Body composition was estimated by dual energy X-ray absorptiometry. Physical activity energy expenditure (AEE) and TEE were assessed using Actiheart accelerometers. The Mini Nutritional Assessment (MNA) was applied and Timed Up and Go (TUG) was measured. RESULTS: AEE was 171, 320 and 497 kcal/day in institutionalized, free living older and young participants, respectively (p < 0.01 between young and older participants). Both absolute TEE and TEE/RMR was higher in young people. Multiple regression analysis accepted age, MNA and TUG as significant predictors of AEE (r2 = 0.24 p < 0.01). CONCLUSION: AEE and PAL were lower among older people, with no differences by institutionalization. PMID- 26545533 TI - [BARRIERS ASSOCIATED WITH BREAST SELF-EXAMINATION AMONG WOMEN 18 TO 50 YEARS OLD: A CROSS SECTIONAL STUDY]. AB - INTRODUCTION: breast cancer is the most common female malignancy and is commonly associated with high levels of morbidity and mortality in developing countries. Breast self-examination (BSE) it is a fundamental method for early detection of the disease. The purpose of the study was to determine the prevalence and barriers associated to BSE in women between 18 to 50 years old. METHODS: a cross sectional study in 627 healthy women between 18 50 years old from Pamplona, Colombia, was performed. Barriers to the practice of BSE (age, marital status, religion, family history for cancer disease, healthcare professionals counseling and social media), were collected by a structured questionnaire. Prevalence was calculated for each factor and associated barriers were established through a multivariate logistic regression models. RESULTS: at the time of the survey, about 72% of women stated they did not practice BSE in the last month and 45% in the last six months. Regression models show that women who belong to the age group between 30 and 39 years old, women who did not have any counseling from a health professional and those who did not report breast cancer in their family history; were associated as barriers for practicing BSE. CONCLUSIONS: the BSE in the study population was low. These data could be used to provide educational intervention programs about the importance of early diagnosis of breast cancer. PMID- 26545534 TI - [FACTORS WHICH INFLUENCE THE LEAN MASS LOSS IN CANCER PATIENTS]. AB - INTRODUCTION: cancer is an important illness in the sanitary field due to phisic and functional consequences involved in it. Among these consequences there is the malnutrition which can cause a loss of lean mass and with it a decrease in the Quality of Life, an increase in hospital stays, social and health costs and so on. The aim of this research is to know which factors can influence in the loss of the lean mass. MATERIAL AND METHODS: it is a cross-sectional study in a sample of 72 patients who receive a radiotherapy with curative intent during a period from February 07th and May 14th, 2014. RESULTS: from this pattern Of the total 64 patients were studied, of which 43.7% of the patients presented loss of lean mass, with 21.8% the percentage of patients losing < 2%, 4.7% those with a loss between 2-5% and > 5%, 17.2% of patients. Among the factors studied that can influence the loss of lean mass, only the presence of digestive symptoms have statistical significance (OR = 3.3 or 6.6, as we take as a reference the percentage loss). CONCLUSIONS: the aim of the health staff who are working with these patients is to avoid the consequences that accompanies the loss of lean mass. For all this, it is very important to act before the digestive symptoms, by anticipating to them, or early implementation of an individualized nutritional intervention. PMID- 26545535 TI - EFFECTIVENESS OF IMMUNONUTRITION ON INFLAMMATORY MARKERS IN PATIENTS WITH CANCER; RANDOMIZED CLINICAL TRIAL. AB - BACKGROUND: malnutrition is a common complication in patients with cancer and is associated with immunosuppression and alterations with inflammatory response. OBJECTIVE: the aim of our study was to evaluate the effect of enteral nutrition supplemented with two enteral formulas on inflammatory markers (CRP, IL-6 and FNTalpha) in cancer patients undergoing chemotherapy. DESIGN AND METHODS: randomized control trial, conducted at the Hospital Juarez of Mexico in patients with cancer undergoing chemotherapy with IRN < 97.5 and SGA B/C. Patients were randomly allocated to two groups: group I (immunomodulatory), group II (high omega3). The intervention began on the first day of chemotherapy until day 10 after. We evaluated nutritional status and an inflammatory marker on days 0, +5, +10 QT. Statistical analysis was performed with T Student, x2 and analysis of variance for repeated measurements. P < 0.05 was considered statistically significant. RESULTS: a total of 29 patients were analyzed, 27 (62.8%) females and 16 (37.2%) males. Mean age 43.91 + 11.3 years old. Malnutrition prevalence was 48.8% moderate and 51.2% severe. Prealbumin levels significantly increase in group II vs group I (p < 0.05). Both groups maintenance body weight, lean mass and fat mass. No decrease levels of CRP, IL-6 and FNTalpha. CONCLUSIONS: enteral supplementation during chemotherapy inhibits nutritional deterioration and maintenance body weight and lean mass. No decreased levels of inflammatory markers. PMID- 26545536 TI - TEST-RETEST RELIABILITY OF A FIELD-BASED PHYSICAL FITNESS ASSESSMENT FOR CHILDREN AGED 3-6 YEARS. AB - OBJECTIVE: the present study aims to determine the test-retest reliability of the Fitness Test Battery in children aged 3-6 years. METHODS: a total of 553 children voluntarily participated in the current study; all children were aged 3 to 6 years. Demographic characteristics reveal that 274 children were male (age: 4.63 +/- 0.94 years old, Body max index [BMI] = 16.30 +/- 2.07 kg/m2), and 279 were female (age 4.70 +/- 0.97 years old, BMI = 16.28 +/- 2.09 kg/m2), and they were selected from 8 schools in southern Spain. All selected tests for the Fitness Test Battery, except the 10 x 20 metres (m) test that was designed ad hoc for this study, have been used in previous studies and are focused on testing basic components of physical condition and motor development such as endurance, strength, speed, reaction time and balance (10 x 20 m, Standing Broad Jump, 20 m running speed, Ruler drop test and Balance). RESULTS: the results obtained in this study indicate that the Fitness Test Battery has obtained adequate reliability parameters, and is able to discriminate with age among the different tests in healthy children between 3 and 6 years old. The tests used were safe, easy to perform, very acceptable and understandable by children. CONCLUSION: the Fitness Test Battery is a valid, reliable and easy to assess the physical fitness of pre-schoolers children. PMID- 26545537 TI - [ANTHROPOMETRIC CHILEAN TABLE TENNIS PLAYERS OF COMPETITIVE FEATURES]. AB - The aim of the study was to characterize the anthropometric profile and somatotype of a sample of 50 players table tennis competitive with an average age 21.6 (+/- 3.1) years belonging to the Chilean team and institutions of higher education in the region of Valparaiso. The evaluation was conducted under the protocol marking the International Society for the Advancement of Kinanthropometry (ISAK) for the measurement procedure 25 restricted profile variables described by Drinkwater, Norton and Olds. Order to determine the body composition, fat, muscle, bone, skin and tissue residual was considered, using the equations proposed by Kerr. The body shape is characterized through somatotype method proposed by Carter. The sample was divided into 4 groups; Chilean Selection, Traditional Private Universities, State Universities and Private Universities Traditional Nontraditional. Regarding body composition; the Chilean team has the highest values of muscle tissue (45.6 +/- 1.7%) and the lowest values of adipose tissue (25.2 +/- 1.8%), also presenting lesser value in the Sigma 6 skinfolds (mm) . The results showed no significant differences between groups in the aforementioned variables. In general somatotype compared by analyzing SANOVA no significant differences between groups (p = 0.409) was observed. The results show a biotype with such a characterization of endo mesomorph with average values (4,1-4,9-1,8). This study provides updated data biotypological reference for this sport that can be used for decision-making. PMID- 26545538 TI - [ASSOCIATION BETWEEN HEALTH RELATED QUALITY OF LIFE, BODYWEIGHT STATUS (BMI) AND PHYSICAL ACTIVITY AND FITNESS LEVELS IN CHILEAN ADOLESCENTS]. AB - AIM: the objective of this study was to analyze the potential relationships between Health Related Quality of Life (HRQoL) with weight status, physical activity (PA) and fitness in Chilean adolescents in both, independent and combined analysis. METHOD: a sample of 767 participants (47.5% females) and aged between 12 and 18 (mean age 15.5) was employed. All measurements were carried out using selfreported instruments and Kidscreen-10, iPAQ and IFIS were used to assess HRQoL, PA and Fitness respectively. One factor ANOVA and linear regression models were applied to analyze associations between HRQoL, weight status, PA and fitness using age and sex as confounders. RESULTS: body mass index, level of PA and fitness were independently associated with HRQoL in Chilean adolescents. However, the combined and adjusted by sex and age analysis of these associations showed that only the fitness was significantly related with HRQoL. CONCLUSION: general fitness is associated with HRQoL independently of sex, age, bodyweight status and level of PA. The relationship between nutritional status and weekly PA with HRQoL are mediated by sex, age and general fitness. PMID- 26545539 TI - [CAFFEINE INTAKE AND ITS EFFECT ON THE MAXIMAL AEROBIC SPEED CORRIDORS 800 -METER ATHLETES]. AB - OBJECTIVES: to check the effects of caffeine intake (3 mg/kg-1) and improved time to exhaustion limit of maximum aerobic speed and could modify blood lactate levels in 800-meter runners. METHODS: the study is based on an experimental design, crossover, randomized and blind. 7 subjects (20 +/- 3 years, 63 +/- 6 kg, and 169.1 +/- 7 cm) 800-meter runners, they should be competing for at least three years and be among the top 10 national ranking. They conducted a test timeout to exhaustion on a treadmill at maximum aerobic speed, where they ingested a capsule could contain caffeine (3 mg/kg-1) or placebo (sucralose). Lactate concentration at the rest and end of each test was measured. RESULTS: caffeine intake showed a significant increase in the duration of the timeout relative to placebo (376 +/- 137-457 +/- 182 sec, respectively, p < 0.05). Regarding the blood lactate, no significant difference between the rest condition, the placebo and caffeine intake (p < 0.05). CONCLUSIONS: the use of caffeine as an ergogenic aid, in doses of 3 mg/kg-1 significantly increased (p < 0.05) TLIM of VAM to exhaustion. This effect is an improvement in the performance of 800-meter runners. In turn, a significant increase in the concentrations of lactate, which could refer to the increase in intensity after caffeine intake work is appreciated. PMID- 26545540 TI - EATING DISORDERS AND DIET MANAGEMENT IN CONTACT SPORTS; EAT-26 QUESTIONNAIRE DOES NOT SEEM APPROPRIATE TO EVALUATE EATING DISORDERS IN SPORTS. AB - INTRODUCTION: there is a growing concern in the appearance of eating disorders in athletes, especially those that practice sports grouped into weight categories. This affects the way athletes eat, using frequently unhealthy strategies to control weight, especially during the pre-competition period. AIM: this study analyses the prevalence of contact sports athletes in developing eating disorders, and how a controlled diet plan can reduce this risk. At the same time, it evaluates the use of the EAT-26 questionnaire to detect such disorders. METHODS: a randomized frequency study was performed on 244 athletes (158 men, 86 women), who were separated into two groups: those that followed a diet plan given by a nutritionist, and a control group on a free diet. The athletes completed an EAT-26 questionnaire while participating in the University-level National Championships. RESULTS: the free diet group scored significantly higher on the questionnaire. Also, the female athletes controlled diet group scored significantly higher than their male counterparts. DISCUSSION: the results of the questionnaire indicate that an adequate nutritional program circumvents the use of unhealthy habits to control body weight and therefore avoids developing particular eating disorders. EAT-26 questionnaire does not seem the most appropriate tool to detect these disorders. PMID- 26545541 TI - A PHYSICAL EDUCATION-BASED STRETCHING PROGRAM PERFORMED ONCE A WEEK ALSO IMPROVES HAMSTRING EXTENSIBILITY IN SCHOOLCHILDREN: A CLUSTER-RANDOMIZED CONTROLLED TRIAL. AB - INTRODUCTION: physical education teachers are required to carry out intervention programs for students to achieve health-enhancing flexibility levels. Unfortunately, to our knowledge, there are no studies examining the effect of a stretching program carried out only once a week on schoolchildren. OBJECTIVES: the purpose of the present study was to compare the effects of a short-term stretching intervention program performed once and twice a week on hamstring extensibility among schoolchildren in the physical education setting. METHODS: a sample of 180 high school students aged 12-14 years old was randomly assigned (by natural groups) to a control group, experimental group 1 and experimental group 2. During physical education classes, experimental group students performed a stretching program for eight weeks. The experimental group 1 and 2 performed the stretching program once and twice a week, respectively. RESULTS: the analysis of variance results showed that the students of both experimental groups improved statistically significantly their hamstring extensibility when compared with the control group students (p < 0.01). Nevertheless, no statistically significant differences between the two experimental groups were found (p > 0.05). CONCLUSIONS: a short-term stretching program performed only once a week improves hamstring extensibility in schoolchildren. When the stretching program is performed twice a week, the improvement in students'hamstring extensibility is not statistically higher. PMID- 26545542 TI - [ASSOCIATION BETWEEN FITNESS, NUTRITIONAL STATUS AND ACADEMIC PERFORMANCE IN PHYSICAL EDUCATION STUDENTS]. AB - INTRODUCTION: several studies demonstrated that regular physical exercise would impact positively on the academic performance of students. OBJECTIVE: to determine the association between physical fitness, nutritional status and academic performance of students of Pedagogy in Physical Education from Temuco, Chile. METHODS: the sample was selected on a non-probabilistic approach, which included 208 subjects (n = 153 women and n = 55 women). The variables studied were physical fitness (short Abs, long jump with feet together, forward trunk flexion, elbow flexion and extension and "course navette" test), nutritional status (BMI) and academic performance (classified as up and down the academic average). RESULTS: 87.5% of students have a satisfactory fitness and a BMI of 23.8 +/- 2.9 kg/m2. The students with the best academic performance were those with the higher proportion of satisfactory physical condition (92.5 %). No association between academic performance and nutritional status was determined, but it was observed between low fitness and a great risk of low academic performance (OR = 2.8, 95% CI 1.0 to 8 1; p < 0.05). CONCLUSION: a relationship between academic achievement and physical fitness among students is observed, but no for the nutritional status and the academic performance. PMID- 26545543 TI - EFFECTS OF TRAINING AND DETRAINING ON GLYCOSYLATED HAEMOGLOBIN, GLYCAEMIA AND LIPID PROFILE IN TYPE-II DIABETICS. AB - OBJECTIVE: the aim of the present study was to determine the effect of training and the consequences of detraining, comparing an aerobic training (AT) protocol with a resistance training (RT) in people with type-II Diabetes Mellitus (DMII). METHODS: a total of 30 individuals participated in the study, with ages ranging from 45 to 50 years, all diagnosed with DMII and not currently receiving pharmacological treatment. Participants were divided at random into an AT group (65% of their maximum aerobic capacity) and a RT group (1 x 2 x 3 protocol at 65% of 1RM). Measurements were taken of weight, body mass index, total cholesterol, HDL-C, LDL-C, triglycerides, glycaemia in a fasted state and glycosylated haemoglobin (HbA1C) at the beginning and at the end of the 6-week training period, and after a further 6 weeks of detraining. RESULTS: the results show that both physical training protocols are capable of inducing significant modifications in lipid profile, glycaemia in a fasted state and levels of HbA1C; however, after stopping the training programme only the RT group maintained the benefits of the reduction in LDL-C, HbA1C and the increase in HDL-C. CONCLUSIONS: resistance exercise in individuals with DMII has an important influence on health and their effects could be maintained even if the training program is interrupted short-term. PMID- 26545544 TI - NUTRITIONAL INTAKE AND NUTRITIONAL STATUS IN ELITE MEXICAN TEENAGERS SOCCER PLAYERS OF DIFFERENT AGES. AB - INTRODUCTION: nutritional intake and status of soccer players has attracted not much research attention. Many soccer players follow an inadequate nutritional intake and have a poor nutritional status. This is relevant in youngsters soccer players, in order to improve performance and promote healthy dietary practices. AIMS: analyze anthropometric characterizes, evaluate nutritional intake and status, dietary habits and pre- and post-exercise meals in elite teenagers soccer players. METHODS: seventy-two young male soccer players (15-20 years) from four junior teams of a soccer Club from the Mexican National Soccer League were measured for height, seat height, weight, 6 skinfolds, 6 diameters and 7 circumferences, height-for-age and BMI-for-age values. Skin, adipose, muscle, bone and residual tissue masses were calculated with the Ross and Kerr equation. Resting energy expenditure and intake was also measured. Daily dietary intake was self-recorded for 4 consecutive days (excluding the match day) using a digital food-weighing scale and a food record questionnaire. Dietary analysis was performed using the NutriBase 7 Clinical software. Several biochemical values were determined. One-way analysis of variance (ANOVA) and post hoc testing was performed using t-tests with a Bonferroni correction. RESULTS: all soccer players were within the normal range values for anthropometric parameters studies, when compared with other adolescent elite soccer teams. Values of plasma glucose, urea, creatinine, uric acid, lipid profile and total proteins were within normal range for young adult population, although albumin levels were high. Moreover, 14% and 20% of soccer players presented hyperuricemia and elevated total cholesterol levels respectively. Energy expenditure and intake were within normal range for all teenager elite soccer players. However, two teams shower significant lower intakes than demands. All macronutrient intakes were within recommendations, except protein that was higher. Micronutrient intake exceeded the recommendations for general population. Soccer players had pre- and post exercise meals with an appropriate range of carbohydrates. Food intake was mainly based on cereals, derivatives and potatoes; meat, poultry, fish, shellfish and eggs and biscuits and confectionery and poor in fruit, vegetables and milk and dairy products. CONCLUSIONS: the population of soccer players did not have optimal nutritional habits. However, their nutritional intake and status was better than in other published studies. The main problems of these teams were that they had a high protein diet and that in some teams the nutritional intake was not enough to cover the demands. Finally, nutritional intake was found to be of poor quality. Thus, we recommend nutritional education for soccer players of these teams. PMID- 26545545 TI - [CONSUMPTION OF OMEGA- 3 FATTY ACIDS AND DEPRESSIVE SYMPTOMS IN COLLEGE STUDENTS FROM SONORA, MEXICO]. AB - INTRODUCTION: recent studies suggest that low serum levels of polyunsaturated fatty acids omega-3 are associated with a higher prevalence of depression. OBJECTIVE: to evaluate whether low consumption of Omega-3 fatty acids is associated with a higher prevalence of depressive symptoms in a sample of college students from the Northwest of Mexico, and to assess the potential effect modification by alcohol consumption. METHODS: we conducted a cross-sectional study in a sample of 706 college students (males and females) aged 18 to 24. The presence of depressive symptoms was identified with the Depression Scale of the Center for Epidemiologic Studies (CES-D), using a cutoff point of >= 24. The intake of omega-3 was obtained by a food frequency questionnaire validated for Mexican population. We estimated the weekly intake of alpha-linolenic fatty acid (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) derived from the diet in mg/g of food. The association between omega-3 from diet and the presence of depressive symptoms was assessed using logistic regression models adjusted for potential confounders. RESULTS: 67% of the participants were females; 16.6% were classified as having depressive symptoms. A low intake of ALA and EPA + DHA was not associated with depressive symptoms before and after adjusting for confounders. Median levels of ALA (from nuts only) were significantly lower among those with depressive symptoms compared to those without these symptoms. CONCLUSIONS: in this population of Mexican college students, a low intake of omega-3 fatty acids was not associated with depressive symptoms. The potential association between nut consumption and depressive symptoms deserve more attention. PMID- 26545546 TI - PREVALENCE OF DISORDERED EATING ATTITUDES AMONG UNIVERSITY STUDENTS IN WUHU, CHINA. AB - OBJECTIVE: the purpose of this study is to assess the current status of disordered eating attitudes and its related factors among University students in Anhui province, and to provide a basis for health intervention. METHODS: this is a cross-sectional study. The University students admitted to the routine health exams were included in current study, and completed self-administered questionnaires which consist of general information and the Eating Attitudes Test 26 (EAT-26). An EAT-26 score of 20 or higher indicated that a person has disordered eating attitudes. Data were analyzed using the SPSS13.0 software. RESULTS: a total of 1 328 subjects (469 male and 859 female), aged 16-24 years from a university in Wuhu were enrolled in this study. In our survey, the proportion of disordered eating attitudes among male, female, total students were 5.3%, 4.0% and 4.5%, respectively. The proportion of disordered eating attitudes among the students whose family annual income < 10000 RMB, 10,000-30,000 RMB, 30,000-60,000 RMB and > 60,000 were 4.2%, 3.9%, 4.3% and 6.9%, respectively. An interesting finding was that the female students are more likely to have disordered eating attitudes if their parents have more education. CONCLUSIONS: our research reveals that the current status of disordered eating attitudes in Anhui province is relatively low. Parents' education level may be related to eating attitudes among University students. It is essential to increase awareness and understanding of eating disorders and its associated risk factors in University students whose parents have higher education. PMID- 26545547 TI - [FOOD CONSUMPTION PATTERN AT A FAMILY LEVEL OF URBAN AREAS OF ANZOATEGUI, VENEZUELA]. AB - In order to assess the qualitative pattern of food consumption in urban families of Anzoategui, Venezuela, 300 domestic groups that combined a total of 1 163 people were studied. The domestic dietary pattern was addressed by the method of qualitative frequency of food consumption, which applied a structured survey that yielded the usual frequency of intake of a food or food group over a given period. The information was obtained through an interview with the person responsible for the procurement of food in every home, and included basic data for the socioeconomic and nutritional profile of the families studied. The qualitative analysis of the diet was obtained by comparing the different food groups that constitute the actual consumption pattern of the population studied, with official feeding guidelines suggested for the Venezuelan population. The present study showed that the qualitative pattern of food consumption in the urban population evaluated is characterized by slightly adjusted to the promotion of health and control of diet-related diseases. The family food proved to be far from the guidelines established by the dietary guidelines for Venezuela and consumption patterns are fairly homogeneous in the different socioeconomic strata. The foods most consumed daily were salt, coffee, dressing and precooked corn flour as well as beef, chicken and the higher weekly food consumption pastas. 90% of the food consumed daily is technologically processed. The results contribute to increase knowledge about the food situation of the Venezuelan population, and technically could direct the efforts of the authorities to reconcile the development of the productive sector and food supply, whereas a pattern qualitatively inadequate intake directly affects the individual biological functioning, and results in the collective conditioning of unfavorable health states. PMID- 26545548 TI - [SATISFACTION WITH HOSPITAL MENU AND INCLUSION OF GOAT CHEESE AS DESSERT COMPARED WITH COW CHEESE]. AB - INTRODUCTION: the evaluation of hospital menus should be performed periodically to suit the needs of patients. Goat cheese may have nutritional benefits, compared to cow cheese. OBJECTIVES: to evaluate patient satisfaction with the hospital menu and with the inclusion of goat cheese, given like dessert in hospital vs menu with cow cheese. METHODS: a survey of hospital menu satisfaction and dessert (goat cheese (GC) vs cow cheese (CC)) in patients with basal diets was conducted. RESULTS: 334 surveys were analyzed. 46.7% were women. The average age was 58.16 +/- 15.15 years and the average stay of 11.21 +/- 11.53. Acceptance of the hospital menu was rated as "good" in a high percentage of respondents (91% Temperature, presentation 94%, humidity 75% and 84% schedule). Overall satisfaction lunch (1 to 10) was 7.31 +/- 2.10 en CC vs 7.39 +/- 1.75 GC (ns) and dessert satisfaction was 6.93 +/- 2.89 vs 6.88 +/- 3.52 (ns) (respectively). CONCLUSIONS: the overall satisfaction with the hospital menu is high and the acceptance of new dessert (QC) is equivalent to acceptance obtained with cow cheese, which could be included in the code of diets. PMID- 26545549 TI - VALIDITY OF A FOOD-FREQUENCY QUESTIONNAIRE FOR ESTIMATING CALCIUM INTAKE IN ADOLESCENT SWIMMERS. AB - INTRODUCTION: accurate estimates of the intake of specific nutrients such as calcium (Ca) are crucial to correctly rank or classify subjects in the distribution of intakes. Therefore, we aimed to estimate the relative validity of a food frequency questionnaire (FFQ) for measuring Ca intake in two different groups of healthy adolescents, a normoactive control group and a physically active group of swimmers with 2 non-consecutive 24h recalls (2 x 24HR) collected as the reference method. METHODS: Pearson correlations, agreement between the 24HR and the FFQ at an individual level and questionnaire's ability to assign individuals to the same quartile of intake as the 24HR were calculated. RESULTS: mean daily Ca intakes were 564.6 mg (SD 232.0) and 895.9 mg (SD 343.1) for the 2 x 24HR and FFQ respectively in controls (P < 0.001); and 731.9 mg (SD 299.8) and 979.8 mg (SD 408.5) for the 2 x 24HR and FFQ respectively in swimmers (P < 0.001). Pearson correlations were 0.52 for controls and 0.47 for swimmers after correcting for intra-variability. Cross-classification analysis indicated that 73.7% of controls and 63.1% of swimmers were classified correctly or in the adjacent category. Also, the 89% of the control group and 79% of swimmers were classified correctly with the FFQ according to the dietary reference intake (DRI) of 1300 mg/d. CONCLUSIONS: for both groups, the FFQ tended to overestimate Ca intake, however it demonstrated fairly good ability to classify subjects into extremes of Ca intake and identified adolescents having Ca intakes lower than the dietary reference intake. PMID- 26545550 TI - [FOOD PATTERNS ASSOCIATED WITH A HEALTY BODY WEIGHT IN CHILEAN STUDENTS OF NUTRITION AND DIETETICS]. AB - OBJETIVE: to determine food patterns and its association with the consumption of various foods with nutritional status of Chilean university students of Nutrition and Dietetics. MATERIAL AND METHODS: cross-sectional study, 634 students were evaluated Nutrition and Dietetics at the Universidad San Sebastian, of Santiago, Concepcion, Valdivia and Puerto Montt. Each student a food survey was applied and an anthropometric assessment. RESULTS: 68% of students eat breakfast daily, 36.1% and 37.1% consume the recommended servings of fruits and vegetables, 64.9% consume soft drinks frequently. A positive association was observed between an adecuated weight and the fact of eat vegetables (>= 2 servings/day) OR = 0.662 (0.440 to 0.996), whole grains OR = 0.474 (0.224 to 1.002), low consumption of fried and sweet snack OR = 0.643 (0.406 to 1.019) and OR = 0.545 (0.360 to 0.825) respectively. CONCLUSIONS: students have an insufficient intake of healthy foods and a high intake of unhealthy foods, also shows that the intake of vegetables, whole grains, low consumption of fried foods and sweet snacks are associated with a normal nutritional status among students evaluated. PMID- 26545551 TI - [FAMILY EATING HABITS AND PERCEPTION OF RISK IN EATING DISORDERS]. AB - INTRODUCTION: factors related to food, shape, weight and exercise, transmitted from parents to children, and media sociocultural factors, such as social networks, also influence the development of Eating Disorders (ED). OBJECTIVES: to analyse the influence of family eating habits and the parents perception about the influence of social networks on the development and maintenance of ED. METHOD: 30 parents of ED patients participated voluntarily in this study fulfilling a series of questionnaires, as well as reporting their weight and height. RESULTS: it is observed an underestimation of weight in the case of overweight (33.33%) and obesity (35%) without considering the fact of going on diet in the future (chi2 = 11.31; p < 0.01). It must be noted that it exists an excessive consumption of meats, snacks and sweets. During weekends it is observed an increased intake of calories and sugar (p < 0.01) and cholesterol (p < 0.05), while the intake of fibre, iron, zinc and magnesium is reduced (p < 0.01). In addition, the consumption of water and bread decreases and other habits seem to be more relevant (e.g. snacking, intake of a single dish) (p < 0.05). DISCUSSION AND CONCLUSIONS: eating habits of ED patients' families improve by means of the nutrition education included in the treatment. Relatives do not perceive adequately the risk of the social networks in their children, which might contribute to the maintenance and future relapses of ED. PMID- 26545552 TI - ASSESSMENT OF GOOD PRACTICES IN HOSPITAL FOOD SERVICE BY COMPARING EVALUATION TOOLS. AB - INTRODUCTION: since food service in hospitals complements medical treatment, it should be produced in proper hygienic and sanitary conditions. It is a well-known fact that food-transmitted illnesses affect with greater severity hospitalized and immunosuppressed patients. AIMS: good practices in hospital food service are evaluated by comparing assessment instruments. METHODS: good practices were evaluated by a verification list following Resolution of Collegiate Directory n. 216 of the Brazilian Agency for Sanitary Vigilance. Interpretation of listed items followed parameters of RCD 216 and the Brazilian Association of Collective Meals Enterprises (BACME). Fisher's exact test was applied to detect whether there were statistically significant differences. Analysis of data grouping was undertaken with Unweighted Pair-group using Arithmetic Averages, coupled to a correlation study between dissimilarity matrixes to verify disagreement between the two methods. RESULTS AND DISCUSSION: Good Practice was classified with mean total rates above 75% by the two methods. There were statistically significant differences between services and food evaluated by BACME instrument. Hospital Food Services have proved to show conditions of acceptable good practices. CONCLUSION: the comparison of interpretation tools based on RCD n. 216 and BACME provided similar results for the two classifications. PMID- 26545553 TI - [MEDERI MODEL NUTRITIONAL CARE HOSPITAL]. AB - INTRODUCTION: the need for nutritional care models, to address the problem of malnutrition in hospitals, involves developing mederi Nutrition Care Model in order to raise the quality of health care, and promote good practices of Clinical Nutrition. To describe the process of nutrition and metabolic support, aimed at measuring the effectiveness of the model, which is currently a center of national and international reference. MATERIALS AND METHODS: descriptive, evaluative, transversal and observational. Includes analysis of consolidated since the implementation of the model in 2008 through 2014. Information The number of study subjects was 163 575, variables to test the efficacy measures were: productivity and perceived quality of nutritional care. RESULTS: made analysis of the key processes in which the model is based, nutritional adult and neonatal hospital care, nutritional support, supervision of food services, and teaching and research, is an increase in productivity of the service 591% , increasing the percentage of patient satisfaction from 50% to 95.8%. CONCLUSION: the success of a model of nutritional care lies in the consolidation of administrative, healthcare facilities, which in turn promotes the development of human talent, teaching and research in nutrition. PMID- 26545554 TI - EFFECT OF SELENIUM SUPPLEMENTATION VIA BRAZIL NUT (BERTHOLLETIA EXCELSA, HBK) ON THYROID HORMONES LEVELS IN HEMODIALYSIS PATIENTS: A PILOT STUDY. AB - BACKGROUND: thyroid function depends on trace mineral selenium (Se), being at the active center of the iodothyronine deiodinase that catalyzes the conversion of the thyroxine (T4) to the active form of thyroid hormone, triiodothyronine (T3). Hemodialysis (HD) patients have reduced T3 levels partly due to impaired hormonal conversion that can be related to Se deficiency, a common feature in these patients. This study evaluated the effect of Brazil nuts (richest Se source) on thyroid hormone levels in HD patients. METHODS: we performed an uncontrolled intervention with 40 HD patients (53.3 ?+/- 16.1 yrs, dialysis vintage 62.0 (8.0 207.0) months) that received one nut (~5g, average 58.1 MUg Se/g) per day for three months. Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation and, serum T3, free T4 (FT4), TSH as well as glutathione peroxidase (GPx) activity were measured by ELISA. RESULTS: all patients were Se deficient and presented low T3 levels at baseline. After intervention, Se plasma levels (from 17.6 ?+/- 11.6 to 153.4 ?+/- 86.1 MUg/L), GPx activity (from 33.7 ?+/- 5.9 to 41.4 ?+/- 11.2 nmol/min/mL), T3 (from 27.3 ?+/- 8.8 to 50.2 +/- 4.8ng/dL) and FT4 levels (0.87 ?+/- 0.2 to 0.98 ?+/- 0.4 ng/dL) were significantly increased (p < 0.05), while TSH levels were reduced (from 2.17 ?+/- 1.3 to 1.96 ?+/- 1.1 uUI/mL), but not significantly. CONCLUSION: in conclusion, increasing Se levels via Brazil nut supplementation was associated with improvement in thyroid hormone levels in HD patients, although the amount of Se given was not able to restore T3 to normal levels. PMID- 26545555 TI - [EFFICIENCY OF HAEMOGLOBIN REGENERATION IN THE NUTRITIONAL FERROPENIC ANAEMIA RECOVERY WITH GOAT MILK-BASED DIETS]. AB - OBJECTIVE: in spite of the high incidence/prevalence of iron deficiency anemia (IDA) and the beneficial effects derived from the consumption of goat milk, scarce is known about the recovery of the anemia following a balanced diet accompanied by the intake of goat milk of goat. The aim of the current study is to assess, in rats with experimentally induced nutritional iron deficiency anemia, the effects of goat or cow milk-based diets, supplied during 30 days, on the recovery of the anemia and the efficiency of regeneration of the hemoglobin. MATERIAL AND METHODS: 40 male Wistar albino rats newly weaned were divided at random in two experimental groups and they were fed ad libitum for 40 days with AIN-93G diet, either with normal iron content (control group, 45 mg/kg diet), or low iron content (anaemic group, 5 mg/kg diet). Samples of blood form the caudal vein were collected for the hematologic control of the anemia. Later, both experimental groups (control and iron deficient) were fed for 30 days with goat or cow milk- based diets. After finishing the experimental period and previous anesthesia the animals were withdrawn by canulation of the abdominal aorta, and the obtained blood was gathered in tubes with EDTA as anticoagulant for the later determination of hematologic parameters and the efficiency of regeneration of the hemoglobin. RESULTS AND DISCUSSION: after the consumption of a diet with low iron content during 40 days, the rats were anaemic, with a concentration of hemoglobin, hematocrit, serum iron, mean corpuscular volume (MCV), serum ferritin and low transferrin (p < 0.001), whereas the levels of platelets and the total iron binding capacity (TIBC) were raised (p < 0.001), findings consistent with the anemia induced experimentally in the animals. The efficiency of regeneration of the hemoglobin was higher in control and anaemic rats fed goat milk-based diet in comparison with those fed cow milk-based diet (p < 0.001) due to, partly, to the major levels of serum iron and hemoglobin, and to the best nutritive utilization of iron in the animals that consumed the goat milk-based diet thanks to the excellent nutritional characteristics of this type of milk. CONCLUSION: the consumption during 30 days of goat or cow milk-based diets favors the recovery of the iron deficiency anemia, especially with the goat milk, due to the major efficiency of regeneration of the hemoglobin, index that shows the quantity of iron of the diet used for the synthesis of hemoglobin. Therefore, it would be recommendable the consumption of goat milk in the context of a balanced diet in healthy populations and, especially in those at risk of suffering iron deficiency. PMID- 26545556 TI - [ANALYSIS OF CARDIOVASCULAR RISK FACTORS IN YOUNG UNIVERSITY STUDENTS ACCORDING TO THEIR NUTRITIONAL STATUS]. AB - BACKGROUND: obesity is one of the most serious not transmissible illnesses and prevalent at present, it is considered a major risk factor for the cardiovascular disease and is associated with the development of insulin resistance, intolerance to the glucose, arterial hypertension and metabolic syndrome. OBJECTIVE: the purpose of the study is to analyze the nutritional status in young university students and its association with cardiovascular risk factors. PATIENTS AND METHODS: there were evaluated 153 university students, 51 men and 102 women between 17 and 33 years old. Anthropometric measurements were made by BMI and waist circumference, systolic and diastolic pressure, cholesterol, HDL cholesterol (HDL), LDL cholesterol (LDL), triglycerides and blood glucose. RESULTS: the variables HDL cholesterol (p = 0.000) and systolic pressure (p = 0.043) showed significant differences in comparison by gender. The 35.29% presented overweight or obesity. In the comparison by nutritional status; the contour waist, systolic and diastolic pressure showed significant differences (p < 0.05). To relate the state nutritional variables with the plasma and the blood pressure, this presented association with cholesterol levels, LDL-cholesterol, systolic and diastolic blood pressure (p < 0.05). The Contour waist presented partnership with the pressure systolic and diastolic (p < 0.05). CONCLUSIONS: there is a high prevalence of malnutrition in the sample of young university students; in addition it is associated with cardiovascular risk factors, being the obese students those who present major deterioration in all the evaluated variables. PMID- 26545557 TI - [CHRONIC KIDNEY DISEASE AND ITS RELATIONSHIP WITH INTAKE OF TURMERIC, CATECHINS, PROANTHOCYANIDINS AND OMEGA-3]. AB - Chronic renal disease is characterized by decreased glomerular filtration rate (GFR) < 60 ml/min/ 1.73m2 and/or the presence of kidney damage independent of the cause for a period of 3 months or more. The treatment of more advanced stages of chronic kidney disease is dialysis, and most common form of hemodialysis. This treatment is costly in our country reaching USD 900 per person. The main cause of admission to dialysis, diabetic nephropathy remains with 34% of all revenue. This alone makes any improvement in the treatment of CKD is highly desirable. There is evidence available about the fundamental role of turmeric, proanthocyanidins, catechins and omega-3 on how these compounds are related to the response to treatment of chronic kidney disease for various reasons. PMID- 26545558 TI - PREVALENCE AND COSTS OF MALNUTRITION IN HOSPITALIZED DYSPHAGIC PATIENTS: A SUBANALYSIS OF THE PREDYCES STUDY. AB - INTRODUCTION: dysphagia and malnutrition are conditions that frequently appear together in hospitalized patients. OBJECTIVES: the main purpose of this study was to analyze the prevalence of malnutrition in patients with dysphagia included in the PREDyCES study as well as to determine its clinical and economic consequences. METHODS: this is a substudy of an observational, cross-sectional study conducted in 31 sites all over Spain. RESULTS: 352 dysphagic patients were included. 45.7% of patients presented with malnutrition (NRS-2002 >= 3) at admission and 42.2% at discharge. In elderly patients (>= 70 years old) prevalence of malnutrition was even higher: 54.6% at admission and 57.5% at discharge. Also, prevalence of malnutrition was higher in urgent admissions versus those scheduled (45.7% vs 33.3%; p < 0.05) and when admitted to small hospitals vs. large hospitals (62.8% vs 43.9%; p < 0.001). In-hospital length of stay was higher in malnourished patients compared to those well-nourished (11.5 +/- 7.1 days vs. 8.8 +/- 6.05 days; p < 0.001), and in malnourished patients a tendency towards increase related-costs was also observed, even though it was not statistically significant (8 004 +/- 5 854 ? vs. 6 967 +/- 5 630 ?; p = 0.11). Length of stay was also higher in elderly patients (>= 70 y/o) vs adults (< 70 y/o). 25% of dysphagic patients and 34.6% of malnourished patients with dysphagia received nutritional support during hospitalization. DISCUSSION: these results confirm that in patients with dysphagia, malnutrition is a prevalent and under recognized condition, that also relates to prolonged hospitalizations. PMID- 26545559 TI - [TOTAL PARENTERAL NUTRITION IN A PREGNANT PATIENT WITH ACUTE PANCREATITIS AND LIPOPROTEIN LIPASE DEFICIENCY]. AB - We present a case of severe acute pancreatitis induced by hypertriglyceridemia secondary to lipoprotein lipase (LPL) deficiency in a pregnant patient with gestational diabetes, initially maneged with diet but it was later necessary to carry out artificial nutricional support measures: total parenteral nutrition. LPL deficiency might cause severe hypertriglyceridemia, repetition acute pancreatitis which is an unwieldy and severe situation during pregnancy. Acute familial hypertriglyceridemia pancreatitis accounts for 5% of cases, including LPL deficiency. The goal of treatment is to reach triglycerides levels below 500 mg/dl, being very low fat diet the treatment of choice, drugs or plasmapheresis techniques can also be associated. TPN enriched in omega3 fatty acids and glutamine was safe and effective in our patient with significant decrease in triglyceride levels. PMID- 26545560 TI - [IN MEMORIAM Victor Jimenez Torres]. PMID- 26545561 TI - Different disulfide bridge connectivity drives alternative folds in highly homologous Brassicaceae trypsin inhibitors. AB - Low-molecular-mass trypsin inhibitors from Arabidopsis thaliana, Brassica napus var. oleifera, and Sinapis alba L. (ATTI, RTI, and MTI, respectively) display more than 69% amino acid sequence identity. Among others, the amino acid sequence Cys-Ala-Pro-Arg-Ile building up the inhibitor reactive site, and the eight Cys residues forming four disulfide bridges are conserved. However, the disulfide bridge connectivity of RTI and MTI (C1-C3, C2-C4, C5-C6, and C7-C8) is different from that of ATTI Cys (C1-C8, C2-C5, C3-C6, and C4-C7). Despite the different disulfide bridge connectivity, the reactive site loop of ATTI, RTI, and MTI is solvent exposed permitting trypsin recognition. Structural considerations here reported suggest that proteins showing high amino acid sequence identity and common functional properties could display different three-dimensional structures. This may reflect high inhibitor plasticity in relation to plant pathogen interactions, plant tissue development as well as the different redox potential of cell compartments. PMID- 26545562 TI - Women with abnormal Pap smear result: a qualitative study of Swedish healthcare professionals' experiences. AB - A Papanicolaou (Pap) smear can be used to detect pre-cancerous cellular changes, so that they can be treated before they develop into cervical cancer. When the results of a Pap smear test are abnormal, women need further investigation, treatment and follow-up. Healthcare professionals (HCPs) are in a position to care for these women with abnormalities. The aim of this study was to explore the experiences of HCPs in caring for women with abnormal Pap smear results. In total, 20 HCPs from two counties in south-eastern Sweden participated in individual interviews, based on two open-ended questions. Interviews were recorded, transcribed verbatim and analysed using content analysis. The results showed that HCPs experienced that abnormal Pap smear results created anxiety in women, who often sought information from the Internet as a way to cope. Furthermore, the HCPs thought that it was a problem that women chose not to attend investigation, treatment and follow-ups. However, information about the seriousness of abnormal Pap smear results causes women to participate. It is a challenge for HCPs to inform in a reassuring manner. Finally, HCPs should collaborate with women to meet their information needs and to also provide support regarding finding and filtering reliable information on the Internet. PMID- 26545563 TI - Up-regulated expression of PTEN after splenetomy may prevent the progression of liver fibrosis in rats. AB - BACKGROUND/PURPOSE: To investigate the mechanisms of delaying progression of liver fibrosis by splenectomy. METHODS: Liver fibrosis was induced by common bile duct ligation. Rats were divided into 3 groups randomly: group A with common bile duct ligation and splenectomy (n = 45), group B with common bile duct ligation and spleen sham operation (n = 45), group C with sham common bile duct ligation and spleen sham operation (n = 45). Liver samples were collected at the 1st, 3rd and 5th week. H&E staining and Sirius staining were used to evaluate the degree of liver fibrosis, immunohistochemical staining was used to measure the expression of alpha-SMA and PTEN. PTEN mRNA and protein expression was measured by real-time PCR and Western-blot. RESULTS: Over time, liver fibrosis developed gradually in group A and B. The expression of PTEN mRNA and protein in group A was higher than that in group B (P < 0.05), while the expression of alpha-SMA was higher in group B (P < 0.05). The expression of PTEN was negatively correlated with alpha-SMA (r = -0.86, P < 0.05). CONCLUSIONS: In this study, splenectomy can up-regulate the expression of PTEN and reduce the secretion of alpha-SMA, thereby deterring the progression of liver fibrosis. PMID- 26545564 TI - How do I interpret a p value? AB - A p-value is a number between 0 and 1 that is extremely useful in interpreting research results. Using comparison of the means of two samples as an example, a p value <0.05 suggests that there is enough evidence to presume a real difference between groups from which the samples were drawn (that the "null hypothesis" can be rejected). We say that the difference between the means is statistically significant. However, it isn't iron clad proof and there is still a chance that there is really no difference. Furthermore, a statistically significant difference may not be clinically significant if it is not enough to appreciably affect patient outcomes. We describe the theory behind p-values and some common errors in interpretation. PMID- 26545565 TI - Clinical utility of rapid pathogen identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in ventilated patients with pneumonia: A pilot study. AB - BACKGROUND AND OBJECTIVE: We evaluated the clinical utility of rapid identification of microorganisms in bronchoalveolar lavage (BAL) fluid using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in terms of the clinical outcomes of ventilated patients with pneumonia. METHODS: Patients for whom microorganisms were identified via MALDI TOF MS (from March 2013 to February 2014; post-intervention group) were compared with patients for whom microorganisms were identified using conventional methods (from March 2012 to February 2013; pre-intervention group). All pneumonia types (community-acquired, hospital-acquired, healthcare-associated and ventilator associated pneumonia) were included in the analysis. RESULTS: In total, 77 patients (50 men, mean age 67.2 +/- 12.5 years) were included (40 patients in the pre-intervention group and 37 in the post-intervention group). The time from BAL fluid collection to microorganism identification and the availability of antimicrobial susceptibility results was shorter in the post- compared with the pre-intervention group (51.9 +/- 11.3 vs 67.3 +/- 17.4 h, P < 0.001). Also, the time from BAL fluid collection to adjustment of antibiotic therapy was shorter in the post-intervention group (56.5 +/- 10.9 vs 73.2 +/- 18.5 h, P < 0.001). Microorganism identification via MALDI-TOF MS was independently associated with a shorter intensive care unit (ICU) stay after BAL fluid was drawn (hazard ratio = 2.324, P = 0.007). CONCLUSION: Rapid identification of microorganisms in BAL fluid via MALDI-TOF MS was associated with adjustment of antibiotic therapy and a shorter ICU stay after BAL fluid was collected from ventilated patients with pneumonia. PMID- 26545566 TI - Designed Synthesis of van der Waals Heterostructures: The Power of Kinetic Control. AB - Selecting specific 2D building blocks and specific layering sequences of van der Waals heterostructures should allow the formation of new materials with designed properties for specific applications. Unfortunately, the synthetic ability to prepare such structures at will, especially in a manner that can be manufactured, does not exist. Herein, we report the targeted synthesis of new metal semiconductor heterostructures using the modulated elemental-reactant technique to nucleate specific 2D building blocks, control their thickness, and avoid epitaxial structures with long-range order. The building blocks, VSe2 and GeSe2 , have different crystal structures, which inhibits cation intermixing. The precise control of this approach enabled us to synthesize heterostructures containing GeSe2 monolayers alternating with VSe2 structural units with specific sequences. The transport properties systematically change with nanoarchitecture and a charge density wave-like transition is observed. PMID- 26545567 TI - A benzenediamine derivative fc-99 attenuates lupus-like syndrome in MRL/lpr mice related to suppression of pDC activation. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with prominent chronic inflammatory aspects. Plasmacytoid dendritic cells (pDCs), which are the principal interferon-alpha (IFN-alpha)-producing cells, have known to be critically involved in SLE pathogenesis. Our previous research demonstrated that a benzenediamine derivative FC-99 possessed anti-inflammatory activities. However, the effects of FC-99 on SLE have not been investigated to date. In this study, we found that FC-99 attenuated lupus-like pathological symptoms and lupus nephritis as well as the expression of pro-inflammatory cytokines in kidneys of MRL/lpr mice. FC-99 also decreased both the total IgM, total IgG and anti-dsDNA IgG levels in sera and the activation of B cells in the PBMCs and spleens of MRL/lpr mice. Moreover, FC-99 inhibited the abnormal activation and number of pDCs from PBMCs and spleens and levels of IFN-alpha in MRL/lpr mice. Notably, FC 99 significantly suppressed the expression of IFN-inducible genes in peripheral blood mononuclear cells (PBMCs) and spleens from MRL/lpr mice. As expected, in vitro experiments demonstrated that FC-99 decreased both the activation and IFN alpha production of pDCs and inhibited IRAK4 phosphorylation in pDCs upon TLR7 and TLR9 stimulation. We further confirm that the inhibition of FC-99 on B cell activation depended on level of pDCs-secreting IFN-alpha. These data indicate that FC-99 attenuated lupus-like syndrome in MRL/lpr mice related to suppression of pDC activation, especially pDCs-secreting IFN-alpha. This study suggests that FC-99 may be a potential therapeutic candidate for the treatment of SLE. PMID- 26545568 TI - Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV positive and negative patients with cervical intraepithelial neoplasia. AB - Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, P<0.04). Considering CIN degree (CIN 1 and CIN 2/3), the HIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (P<0.018) and 54.5% (P<0.0048). The HIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1. PMID- 26545569 TI - Words of Wisdom. Re: Androgen Deprivation Therapy plus Docetaxel and Estramustine Versus Androgen Deprivation Therapy Alone for High-risk Localised Prostate Cancer (GETUG 12): A Phase 3 Randomised Controlled Trial. PMID- 26545570 TI - Words of Wisdom. Re: Predicting Life Expectancy in Men Diagnosed with Prostate Cancer. PMID- 26545571 TI - Words of Wisdom. Re: The Relationship Between Irritable Bowel Syndrome, Functional Dyspepsia, Chronic Fatigue and Overactive Bladder Syndrome: A Controlled Study 6 Years After Acute Gastrointestinal Infection. PMID- 26545572 TI - Words of Wisdom. Re: Risk of Damage to the Somatic Innervation of the Penis during the AdVanceTM Procedure: An Anatomical Study. PMID- 26545573 TI - Words of Wisdom. Re: X-Linked TEX11 Mutations, Meiotic Arrest, and Azoospermia in Infertile Men. PMID- 26545574 TI - Words of Wisdom. RE: Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma. PMID- 26545575 TI - Primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin: Diagnostic clues and distinction from other ocular adnexal diseases. AB - A 60-year-old man developed a rubbery thickening and erythema of his left lateral upper and lower eyelids and lateral canthus over several months. He was treated for an extended period of time for blepharitis and chalazia. Incisional biopsy eventually disclosed microscopically a hypercellular lymphoid population sparing the epidermis that surrounded adnexal structures and infiltrated between orbicularis muscle fibers. Immunohistochemically, the lesion was found to be composed of neoplastic, kappa-restricted B cells with an equal number of reactive T cells and small reactive follicles. The diagnosis was a primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin (EMZL). We review the distinguishing clinical, histopathologic, and immunohistochemical features of cutaneous EMZL and contrast those with EMZL of other ocular adnexal sites. Also offered is a differential diagnosis of cutaneous lymphomas of the eyelid skin, which are predominately T-cell lesions. PMID- 26545576 TI - A major trauma course based on posters, audio-guides and simulation improves the management skills of medical students: Evaluation via medical simulator. AB - BACKGROUND: Medical competence requires the acquisition of theoretical knowledge and technical skills. Severe trauma management teaching is poorly developed during internship. Nevertheless, the basics of major trauma management should be acquired by every future physician. For this reason, the major trauma course (MTC), an educational course in major traumatology, has been developed for medical students. Our objective was to evaluate, via a high fidelity medical simulator, the impact of the MTC on medical student skills concerning major trauma management. METHODS: The MTC contains 3 teaching modalities: posters with associated audio-guides, a procedural workshop on airway management and a teaching session using a medical simulator. Skills evaluation was performed 1 month before (step 1) and 1 month after (step 3) the MTC (step 2). Nineteen students were individually evaluated on 2 different major trauma scenarios. The primary endpoint was the difference between steps 1 and 3, in a combined score evaluating: admission, equipment, monitoring and safety (skill set 1) and systematic clinical examinations (skill set 2). RESULTS: After the course, the combined primary outcome score improved by 47% (P<0.01). Scenario choice or the order of use had no significant influence on the skill set evaluations. CONCLUSION: This study shows improvement in student skills for major trauma management, which we attribute mainly to the major trauma course developed in our institution. PMID- 26545577 TI - alpha-Defensin Accuracy to Diagnose Periprosthetic Joint Infection-Best Available Test? AB - BACKGROUND: The purpose of this study was to test the accuracy of a single synovial fluid biomarker, alpha-defensin, in diagnosing periprosthetic joint infection in revision total hip and revision total knee arthroplasty. METHODS: A total of 102 patients comprising 116 revision total hip arthroplasty and revision total knee arthroplasty procedures performed between May 2013 and March 2014 were prospectively evaluated. Cases were categorized as infected or notinfected using Musculoskeletal Infection Society criteria. Synovial fluid was obtained and tested for alpha-defensin using a commercially available kit (Synovasure [CD Diagnostics, Baltimore, Maryland]). RESULTS: For first-stage and single-stage revisions, the alpha-defensin test had a sensitivity of 100% (95% confidence interval [CI], 86%-100%) and a specificity of 98% (95% CI, 90%-100%) with a positive predictive value of 96% (95% CI, 80%-99%) and negative predictive value of 100% (95% CI, 93%-100%). CONCLUSION: A positive alpha-defensin test result was significantly more sensitive and specific for predicting infection than current diagnostic testing and should be considered when managing periprosthetic joint infection. LEVEL OF EVIDENCE: Level III, Study of Diagnostic Test. PMID- 26545578 TI - Multi-Level Light Capture Control in Plants and Green Algae. AB - Life on Earth relies on photosynthesis, and the ongoing depletion of fossil carbon fuels has renewed interest in phototrophic light-energy conversion processes as a blueprint for the conversion of atmospheric CO2 into various organic compounds. Light-harvesting systems have evolved in plants and green algae, which are adapted to the light intensity and spectral composition encountered in their habitats. These organisms are constantly challenged by a fluctuating light supply and other environmental cues affecting photosynthetic performance. Excess light can be especially harmful, but plants and microalgae are equipped with different acclimation mechanisms to control the processing of sunlight absorbed at both photosystems. We summarize the current knowledge and discuss the potential for optimization of phototrophic light-energy conversion. PMID- 26545579 TI - The Relative Value Unit: History, Current Use, and Controversies. AB - The relative value unit (RVU) is an important measuring tool for the work performed by physicians, and is currently used in the United States to calculate physician reimbursement. An understanding of radiology RVUs and current procedural terminology codes is important for radiologists, trainees, radiology managers, and administrators, as this knowledge would help them to understand better their current productivity and reimbursement, as well as controversies regarding reimbursement, and permit them to adapt to reimbursement changes that may occur in the future. This article reviews the components of the RVU and how radiology payment is calculated, highlights trends in RVUs and resultant payment for diagnostic and therapeutic imaging and examinations, and discusses current issues involving RVU and current procedural terminology codes. PMID- 26545580 TI - Combined immunodeficiency due to JAK3 mutation in a child presenting with skin granuloma. PMID- 26545581 TI - Development and characterization of microsatellite loci for common raven (Corvus corax) and cross species amplification in other Corvidae. AB - BACKGROUND: A priority for conservation is the identification of endemic populations. We developed microsatellite markers for common raven (Corvus corax), a bird species with a Holarctic distribution, to identify and assess endemic populations in Alaska. RESULTS: From a total of 50 microsatellite loci, we isolated and characterized 15 loci. Eight of these loci were polymorphic and readily scoreable. Eighteen to 20 common ravens from Fairbanks, Alaska were genotyped showing the following variability: 3-8 alleles per locus, 0.25-0.80 observed heterozygosity (Ho), and 0.30-0.80 expected heterozygosity (He). All loci were in Hardy-Weinberg equilibrium and linkage equilibrium and many loci amplified and were polymorphic in related taxa. CONCLUSIONS: These loci will be used to identify endemic populations of common raven and assess their genetic diversity and connectivity. PMID- 26545582 TI - Mixed method evaluation of a community-based physical activity program using the RE-AIM framework: practical application in a real-world setting. AB - BACKGROUND: Communities are a pivotal setting in which to promote increases in child and adolescent physical activity behaviours. Interventions implemented in these settings require effective evaluation to facilitate translation of findings to wider settings. The aims of this paper are to i) present findings from a RE AIM evaluation of a community-based physical activity program, and ii) review the methodological challenges faced when applying RE-AIM in practice. METHODS: A single mixed-methods case study was conducted based on a concurrent triangulation design. Five sources of data were collected via interviews, questionnaires, archival records, documentation and field notes. Evidence was triangulated within RE-AIM to assess individual and organisational-level program outcomes. RESULTS: Inconsistent availability of data and a lack of robust reporting challenged assessment of all five dimensions. Reach, Implementation and setting-level Adoption were less successful, Effectiveness and Maintenance at an individual and organisational level were moderately successful. Only community-level Adoption was highly successful, reflecting the key program goal to provide community-wide participation in sport and physical activity. CONCLUSIONS: This research highlighted important methodological constraints associated with the use of RE AIM in practice settings. Future evaluators wishing to use RE-AIM may benefit from a mixed-method triangulation approach to offset challenges with data availability and reliability. PMID- 26545584 TI - Automatic detection of abnormalities in mammograms. AB - BACKGROUND: In recent years, an increased interest has been seen in the area of medical image processing and, as a consequence, Computer Aided Diagnostic (CAD) systems. The basic purpose of CAD systems is to assist doctors in the process of diagnosis. CAD systems, however, are quite expensive, especially, in most of the developing countries. Our focus is on developing a low-cost CAD system. Today, most of the CAD systems regarding mammogram classification target automatic detection of calcification and abnormal mass. Calcification normally indicates an early symptom of breast cancer if it appears as a small size bright spot in a mammogram image. METHODS: Based on the observation that calcification appears as small bright spots on a mammogram image, we propose a new scale-specific blob detection technique in which the scale is selected through supervised learning. By computing energy for each pixel at two different scales, a new feature "Ratio Energy" is introduced for efficient blob detection. Due to the imposed simplicity of the feature and post processing, the running time of our algorithm is linear with respect to image size. RESULTS: Two major types of calcification, microcalcification and macrocalcification have been identified and highlighted by drawing a circular boundary outside the area that contains calcification. Results are quite visible and satisfactory, and the radiologists can easily view results through the final detected boundary. CONCLUSIONS: CAD systems are designed to help radiologists in verifying their diagnostics. A new way of identifying calcification is proposed based on the property that microcalcification is small in size and appears in clusters. Results are quite visible and encouraging, and can assist radiologists in early detection of breast cancer. PMID- 26545583 TI - MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer. AB - BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) remains a prevalent and devastating disease. Recently, there has been an increase in SCCHN cases that are associated with high-risk human papillomavirus (HPV) infection. The clinical characteristics of HPV-positive and HPV-negative SCCHN are known to be different but their molecular features are only recently beginning to emerge. MicroRNAs (miRNAs, miRs) are small, non-coding RNAs that are likely to play significant roles in cancer initiation and progression where they may act as oncogenes or tumor suppressors. Previous studies in our laboratory showed that miR-363 is overexpressed in HPV-positive compared to HPV-negative SCCHN cell lines, and the HPV type 16-E6 oncoprotein upregulates miR-363 in SCCHN cell lines. However, the functional role of miR-363 in SCCHN in the context of HPV infection remains to be elucidated. METHODS: We analyzed miR-363 levels in SCCHN tumors with known HPV-status from The Cancer Genome Atlas (TCGA) and an independent cohort from our institution. Cell migration studies were conducted following the overexpression of miR-363 in HPV-negative cell lines. Bioinformatic tools and a luciferase reporter assay were utilized to confirm that miR-363 targets the 3'-UTR of myosin 1B (MYO1B). MYO1B mRNA and protein expression levels were evaluated following miR-363 overexpression in HPV-negative SCCHN cell lines. Small interfering RNA (siRNA) knockdown of MYO1B was performed to assess the phenotypic implication of reduced MYO1B expression in SCCHN cell lines. RESULTS: MiR-363 was found to be overexpressed in HPV-16-positive compared to the HPV negative SCCHN tumors. Luciferase reporter assays performed in HPV-negative JHU028 cells confirmed that miR-363 targets one of its two potential binding sites in the 3'UTR of MYO1B. MYO1B mRNA and protein levels were reduced upon miR 363 overexpression in four HPV-negative SCCHN cell lines. Increased miR-363 expression or siRNA knockdown of MYO1B expression reduced Transwell migration of SCCHN cell lines, indicating that the miR-363-induced migration attenuation of SCCHN cells may act through MYO1B downregulation. CONCLUSIONS: These findings demonstrate that the overexpression of miR-363 reduces cellular migration in head and neck cancer and reveal the biological relationship between miR-363, myosin 1b, and HPV-positive SCCHN. PMID- 26545585 TI - Cost-effectiveness of using the Cervex-Brush (broom) compared to the elongated spatula for collection of conventional cervical cytology samples within a high burden HIV setting: a model-based analysis. AB - BACKGROUND: From 2010 to 2014, approximately 2 million Pap smears from HIV infected women were submitted to the South African National Health Laboratory Services (NHLS) through the national cervical cancer screening programme. The objective of this analysis was to determine whether using the plastic Cervex brush ("broom") would be a cost-effective approach to improve cytology specimen quality as compared to the wooden spatula used currently. METHODS: A decision analysis model was built using the expected adequacy rates for samples collected with the spatula (<$0.02) and broom ($0.23) and the probability of detecting cervical dysplasia. NHLS data was used for testing volumes and rates of HIV positivity, suitability of specimens, and presence of endocervical cells. Expected positivity of Pap smears in HIV-infected women (73 %), odds ratios of the effectiveness of the broom (OR: 1.57), and improved sensitivity when endocervical cells present (OR: 1.89) are from literature. NHLS costs were used for the collection devices and conventional cytology ($4.89). Cost of clinic visit is from WHO CHOICE ($8.36). RESULTS: In 2010, 80 % of specimens submitted to NHLS were adequate for evaluation; in 2014, only 54 % met the same criteria. For HIV-infected women, according to the guidelines model, using the wooden spatula costs $6.25 million per year, $16.79 per woman tested. Under intended practice, for each additional HSIL case detected among HIV-infected women, the South African cervical cancer screening programme could save $13.64 (95 % CI: $13.52 to $13.76) by using the broom as its standard of care collection device through increased collection of endocervical cells and consequent reduction in repeat Pap smears. CONCLUSION: Under a wide range of parameters tested using a simulation model, the more expensive plastic broom could save the South African cervical cancer screening programme money and increase detection of high-grade cervical dysplasia in HIV-infected women compared to the current wooden spatula. PMID- 26545586 TI - Identification and characterization of a new type of inhibitor against the human immunodeficiency virus type-1 nucleocapsid protein. AB - BACKGROUND: The human immunodeficiency virus type-1 (HIV-1) nucleocapsid protein (NC) is an essential and multifunctional protein involved in multiple stages of the viral life cycle such as reverse transcription, integration of proviral DNA, and especially genome RNA packaging. For this reason, it has been considered as an attractive target for the development of new anti-HIV drugs. Although a number of inhibitors of NC have been reported thus far, the search for NC-specific and functional inhibitor(s) with a good antiviral activity continues. RESULTS: In this study, we report the identification of A1752, a small molecule with inhibitory action against HIV-1 NC, which shows a strong antiviral efficacy and an IC50 around 1 MUM. A1752 binds directly to HIV-1 NC, thereby inhibiting specific chaperone functions of NC including Psi RNA dimerization and complementary trans-activation response element (cTAR) DNA destabilization, and it also disrupts the proper Gag processing. Further analysis of the mechanisms of action of A1752 also showed that it generates noninfectious viral particles with defects in uncoating and reverse transcription in the infected cells. CONCLUSIONS: These results demonstrate that A1752 is a specific and functional inhibitor of NC with a novel mode of action and good antiviral efficacy. Thus, this agent provides a new type of anti-HIV NC inhibitor candidate for further drug development. PMID- 26545587 TI - Transcriptome-wide analysis supports environmental adaptations of two Pinus pinaster populations from contrasting habitats. AB - BACKGROUND: Maritime pine (Pinus pinaster Aiton) grows in a range of different climates in the southwestern Mediterranean region and the existence of a variety of latitudinal ecotypes or provenances is well established. In this study, we have conducted a deep analysis of the transcriptome in needles from two P. pinaster provenances, Leiria (Portugal) and Tamrabta (Morocco), which were grown in northern Spain under the same conditions. RESULTS: An oligonucleotide microarray (PINARRAY3) and RNA-Seq were used for whole-transcriptome analyses, and we found that 90.95% of the data were concordant between the two platforms. Furthermore, the two methods identified very similar percentages of differentially expressed genes with values of 5.5% for PINARRAY3 and 5.7% for RNA Seq. In total, 6,023 transcripts were shared and 88 differentially expressed genes overlapped in the two platforms. Among the differentially expressed genes, all transport related genes except aquaporins were expressed at higher levels in Tamrabta than in Leiria. In contrast, genes involved in secondary metabolism were expressed at higher levels in Tamrabta, and photosynthesis-related genes were expressed more highly in Leiria. The genes involved in light sensing in plants were well represented in the differentially expressed groups of genes. In addition, increased levels of hormones such as abscisic acid, gibberellins, jasmonic and salicylic acid were observed in Leiria. CONCLUSIONS: Both transcriptome platforms have proven to be useful resources, showing complementary and reliable results. The results presented here highlight the different abilities of the two maritime pine populations to sense environmental conditions and reveal one type of regulation that can be ascribed to different genetic and epigenetic backgrounds. PMID- 26545588 TI - Stillbirth and congenital anomalies in migrants in Europe. AB - The risk of giving birth to a stillborn child or a child with severe congenital anomaly is higher for women who have immigrated to Europe as compared to the majority population in the receiving country. The literature, however, reveals great differences between migrant groups, even within migrants from low-income countries, although there is no clear pattern regarding refugee or non-refugee status. This heterogeneity argues against a particular migration-related explanation. There are social disparities in stillbirth risk worldwide, and it has been suggested that the demonstrated ethnic disparity is a result of the socioeconomic disadvantage most migrants face. Consanguinity has been considered as another cause for the increased stillbirth risk and the high risk of congenital anomaly observed in many migrant groups. Utilization and quality of care during pregnancy and childbirth is the third major aspect. All three factors seem to contribute to stillbirth risk, and they should be considered in clinical practice and public health. PMID- 26545589 TI - Patient-centered outcomes research in appendicitis in children: Bridging the knowledge gap. AB - PURPOSE: Patient-centered outcomes research (PCOR) aims to give patients a better understanding of the treatment options to enable optimal decision-making. As nonoperative alternatives are now being evaluated in children for acute appendicitis, we surveyed patients and their families regarding their knowledge of appendicitis and evaluated whether providing basic medical information would affect their perception of the disease and allow them to more rationally consider the treatment alternatives. METHODS: Families of children aged 5-18 presenting to the Emergency Department with suspected appendicitis were recruited for a tablet based interactive educational survey. One hundred subjects (caregivers and patients >= 15 years) were questioned before and after an education session about their understanding of appendicitis, including questions on three hypothetical treatment options: urgent appendectomy, antibiotics alone, or initial antibiotics followed by elective appendectomy. Subjects were clearly informed that urgent appendectomy is currently the standard of care. RESULTS: Only 14% of respondents correctly identified the mortality rate of appendicitis (17 deaths/year according to the 2010 US census) when compared with other extremely rare causes of death. Fifty-four and 31% thought it was more common than death from lightning (40/year) and hunting-associated deaths (44/year), respectively. Eighty-two percent of respondents believed it "likely" or "very likely" that the appendix would rupture if operation was at all delayed, and 81% believed that rupture of the appendix would rapidly lead to severe complications and death. In univariate analysis, this perception was significantly more prevalent for mothers (odds ratio, (OR) 5.19, confidence interval (CI) 1.33-21.15), and subjects who knew at least one friend or relative who had a negative experience with appendicitis (OR 5.53, CI 1.40-25.47). Following education, these perceptions changed significantly (53% still believed that immediate operation was necessary, and 47% believed perforation led to great morbidity and potential mortality, P<0.001). In a survey of potential appendicitis treatment options, urgent appendectomy was considered a "good" or "very good" option by 74% of subjects, compared with 68% for antibiotics only without appendectomy and 49% for initial antibiotic therapy followed by elective outpatient appendectomy. CONCLUSION: There was a striking knowledge gap in the participant perception of appendicitis. Appropriate education can correct anecdotally supported misconceptions. Adequate education may empower patients to make better-informed decisions about their medical care and may be important for future studies in alternative treatments for appendicitis in children. PMID- 26545590 TI - Intermittent bout exercise training down-regulates age-associated inflammation in skeletal muscles. AB - Aging is characterized by the progressive decline in mass and function of the skeletal muscle along with increased susceptibility to inflammation, oxidative stress, and atrophy. In this study, we investigate the effect of intermittent bout and single bout exercise training on inflammatory molecules in young (3 months) and old (22 months) male Sprague-Dawley rats. The rats were divided into 6 groups. Young and old rats were randomly assigned for control and two exercise training groups, single bout (S type): 30 min/day, 5 days/week for 6 weeks and intermittent bout (I type): three times for 10 min/day, 5 days/week for 6 weeks respectively. The exercise training was carried out by a treadmill at a speed of 15m/min (young) or 10 m/min (old) with a slope of 5 degrees . After 48 h of the final exercise bout, muscle samples were collected for biochemical assay. I type exercise training reduced the serum levels of inflammatory molecules such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and malondialdehyde (MDA) in old rats. By contrast, interleukin-4 (IL-4) and superoxide dismutase (SOD) were elevated. Consequently in skeletal muscles, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were decreased significantly in the old group of I type. However, the matrix metalloproteinase-2 (MMP-2) level had no positive effects. Also, phosphorylation of mammalian target of rapamycin (p-mTOR) and myogenic differentiation (MyoD) were increased markedly in S and I types of old rats. These results suggest that I type exercise training appears more effective to reduce age-associated inflammatory molecules, and may recommend in regulating against chronic complicated disease induced by aging. PMID- 26545591 TI - [Aborted sudden death in a cocaine consumer]. PMID- 26545592 TI - Phylogeny of the Ampelocissus-Vitis clade in Vitaceae supports the New World origin of the grape genus. AB - The grapes and the close allies in Vitaceae are of great agronomic and economic importance. Our previous studies showed that the grape genus Vitis was closely related to three tropical genera, which formed the Ampelocissus-Vitis clade (including Vitis, Ampelocissus, Nothocissus and Pterisanthes). Yet the phylogenetic relationships of the four genera within this clade remain poorly resolved. Furthermore, the geographic origin of Vitis is still controversial, because the sampling of the close relatives of Vitis was too limited in the previous studies. This study reconstructs the phylogenetic relationships within the clade, and hypothesizes the origin of Vitis in a broader phylogenetic framework, using five plastid and two nuclear markers. The Ampelocissus-Vitis clade is supported to be composed of five main lineages. Vitis includes two described subgenera each as a monophyletic group. Ampelocissus is paraphyletic. The New World Ampelocissus does not form a clade and shows a complex phylogenetic relationship, with A. acapulcensis and A. javalensis forming a clade, and A. erdvendbergiana sister to Vitis. The majority of the Asian Ampelocissus species form a clade, within which Pterisanthes is nested. Pterisanthes is polyphyletic, suggesting that the lamellate inflorescence characteristic of the genus represents convergence. Nothocissus is sister to the clade of Asian Ampelocissus and Pterisanthes. The African Ampelocissus forms a clade with several Asian species. Based on the Bayesian dating and both the RASP and Lagrange analyses, Vitis is inferred to have originated in the New World during the late Eocene (39.4Ma, 95% HPD: 32.6-48.6Ma), then migrated to Eurasia in the late Eocene (37.3Ma, 95% HPD: 30.9-45.1Ma). The North Atlantic land bridges (NALB) are hypothesized to be the most plausible route for the Vitis migration from the New World to Eurasia, while intercontinental long distance dispersal (LDD) cannot be eliminated as a likely mechanism. PMID- 26545593 TI - Body size perception and ideal body size in overweight and obese young adult women. AB - PURPOSE: The purpose of this study was to examine the differences among actual body size, perceived body size, and ideal body size in overweight and obese young adult women. METHODS: Actual body size was assessed by body mass index (BMI), while self-perceived and ideal body sizes were assessed by the Body image assessment tool-body dimension. Descriptive statistics were calculated and analysis of variance (ANOVA) was performed on actual BMI as a function of perceived BMI. RESULTS: Of the 42 participants included in the study, 12 were overweight (25 <= BMI < 30), 18 were obese 1 (30 <= BMI < 35), and 12 were obese 2 (35 <= BMI <= 39.48). The mean ideal body size of participants was 25.34 +/- 1.33. Participants in general perceived their body size (BMI: 35.82 +/- 1.06) to be higher than their actual body size (32.84 +/- 0.95). Overweight participants had a significantly higher mean body size misperception than obese 2 individuals (u dif = -6.68, p < .001). CONCLUSION: Perception accuracy of body size differs in women by BMI. Weight loss programs need to be tailored to consider body size misperception in order to improve treatment outcomes for overweight and obese young women. PMID- 26545594 TI - My mother told me: the roles of maternal messages, body image, and disordered eating in maladaptive exercise. AB - PURPOSE: The current study examined the relevance of familial environment (negative maternal messages) to the phenomenon of maladaptive (obligatory) exercise, defined as exercise fixation. Weight/shape concerns and exercise frequency were examined as potential mediators, evaluated both with and without eating disorder symptoms as a covariate. METHOD: Self-report data comprising sociodemographic details and measures of parental weight messages, body image, obligatory exercise, and disordered eating symptoms were completed by 298 young female attendees of health and fitness centres. RESULTS: The frequency of negative maternal messages demonstrated significant associations with all of weight/shape concerns, exercise frequency, exercise fixation, and eating disorder symptoms. In the initial model, partial mediation of maternal messages to exercise fixation was evident as negative maternal messages continued to have a direct effect on exercise fixation. In the second model, with the inclusion of eating disorder symptoms as a covariate, this direct effect was maintained while mediation was no longer evident. CONCLUSIONS: The data provide further support for the association between disordered eating symptoms and maladaptive exercise, as defined by exercise fixation. Nevertheless, the importance of negative maternal messages as a key environmental enabler of exercise fixation has been demonstrated, even after the effects of weight/shape concerns and exercise frequency were accounted for. Clinically, addressing weight-related talk in the family home may reduce the incidence of problematic cognitions and behaviours associated with both maladaptive exercise and disordered eating symptoms. PMID- 26545596 TI - [Report on the 2015 meeting of the working group on hematopathology in Frankfurt]. PMID- 26545595 TI - The use of a numerical model to simulate the cavo-pulmonary assistance in Fontan circulation: a preliminary verification. AB - The lack of an established experience on the use of VAD for the cavo-pulmonary assistance leads to the need of dedicated VADs development and animal experiments. A dedicated numerical model could support clinical and experimental strategies design and new VADs testing. The aim of this work is to perform a preliminary verification of a lumped parameter model of the cardiovascular system to simulate Fontan physiology and the effect of cavo-pulmonary assistance. Literature data of 4 pigs were used to simulate animals' baseline, and then the model was tested in simulating Fontan circulation and cavo-pulmonary-assisted condition comparing the simulation outcome (Sim) with measured literature data (Me). The results show that the numerical model can well reproduce experimental data in all three conditions (baseline, Fontan and assisted Fontan) [cardiac output (l/min): Me = 2.8 +/- 1.7, Sim = 2.8 +/- 1.8; ejection fraction (%): Me = 57 +/- 17, Sim = 54 +/- 17; arterial systemic pressure (mmHg): Me = 41.8 +/- 18.6, Sim = 43.8 +/- 18.1; pulmonary arterial pressure (mmHg): Me = 15.4 +/- 8.9, Sim = 17.7 +/- 9.9; caval pressure (mmHg): Me = 6.8 +/- 4.1, Sim = 7 +/- 4.6]. Systolic elastance, arterial systemic and arterial pulmonary resistances increase (10, 69, and 100 %) passing from the biventricular circulation to the Fontan physiology and then decrease (21, 39, and 50 %) once the VAD was implanted. The ventricular external work decreases (71 %) passing from the biventricular circulation to the Fontan physiology and it increases three times after the VAD implantation in parallel with the VAD power consumption. A numerical model could support clinicians in an innovative and challenging field as the use of VAD to assist the Fontan physiology and it could be helpful to personalize the VAD insertion on the base of ventricular systo-diastolic function, circulatory parameters and energetic variables. PMID- 26545597 TI - [Laudation for Prof. Dr. Dr. h.c. Manfred Dietel: Awarding of the Rudolf Virchow Medal 2015 of the German Society of Pathology]. PMID- 26545599 TI - The interaction of two-spotted spider mites, Tetranychus urticae Koch, with Cry protein production and predation by Amblyseius andersoni (Chant) in Cry1Ac/Cry2Ab cotton and Cry1F maize. AB - Crops producing insecticidal crystal (Cry) proteins from the bacterium, Bacillus thuringiensis (Bt), are an important tool for managing lepidopteran pests on cotton and maize. However, the effects of these Bt crops on non-target organisms, especially natural enemies that provide biological control services, are required to be addressed in an environmental risk assessment. Amblyseius andersoni (Acari: Phytoseiidae) is a cosmopolitan predator of the two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae), a significant pest of cotton and maize. Tri-trophic studies were conducted to assess the potential effects of Cry1Ac/Cry2Ab cotton and Cry1F maize on life history parameters (survival rate, development time, fecundity and egg hatching rate) of A. andersoni. We confirmed that these Bt crops have no effects on the biology of T. urticae and, in turn, that there were no differences in any of the life history parameters of A. andersoni when it fed on T. urticae feeding on Cry1Ac/Cry2Ab or non-Bt cotton and Cry1F or non-Bt maize. Use of a susceptible insect assay demonstrated that T. urticae contained biologically active Cry proteins. Cry proteins concentrations declined greatly as they moved from plants to herbivores to predators and protein concentration did not appear to be related to mite density. Free-choice experiments revealed that A. andersoni had no preference for Cry1Ac/Cry2Ab cotton or Cry1F maize-reared T. urticae compared with those reared on non-Bt cotton or maize. Collectively these results provide strong evidence that these crops can complement other integrated pest management tactics including biological control. PMID- 26545600 TI - Perceptions of Secondhand and Thirdhand Smoke Among Hispanic Residents of Multiunit Housing. AB - Despite the progressive adoption of smoking bans in public spaces, children living in multi-unit housing remain at risk of exposure to secondhand smoke (SHS) and thirdhand smoke (THS). Hispanic populations in California are particularly vulnerable to the harmful effects of SHS and THS because a large proportion of Hispanics live in multi-unit housing. Three focus groups were conducted in the fall of 2012 (in Spanish and English, N = 24) to understand Hispanics' knowledge of and experiences with SHS and THS, including barriers to avoiding smoke exposure and strategies for protecting their homes from smoke. Hispanic residents reported unpleasant experiences with SHS and THS and were generally knowledgeable about the adverse health effects, although they were not familiar with the term "thirdhand smoke." Some participants also mentioned marijuana smoke as a potential health hazard. Hispanic cultural values made participants reluctant to confront their neighbors but also motivated them to find ways to protect their families from smoke. Potential solutions included working with the smokers to designate a smoking area and gaining support from the building owners. Broad smoking policies should be implemented to help Hispanic residents overcome cultural and social barriers to smoke free air. PMID- 26545601 TI - Relationship between neutrophil-lymphocyte ratio and in-hospital mortality. PMID- 26545598 TI - Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions. AB - A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu interieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area. PMID- 26545602 TI - Patient satisfaction in cardiology after cardiac catheterization : Effects of treatment outcome, visit characteristics, and perception of received care. AB - BACKGROUND: Patient satisfaction is a key indicator for quality of care. However, recent data on determinants of satisfaction in invasive cardiology are lacking. Hence this study was conducted to identify determinants of patient satisfaction after hospitalization for cardiac catheterization. PATIENTS AND METHODS: Data were obtained from 811 randomly selected patients discharged from ten hospitals responding to a mailed post-visit questionnaire. The satisfaction dimension was measured with a validated 42-item inventory assessing demographic and visit characteristics as well as medical, organizational, and service aspects of received care. Bivariate and multivariate statistical analyses were performed to identify predictors of satisfaction. RESULTS: Patients were most satisfied with the kindness of medical practitioners and nurses. The lowest ratings were observed for discharge procedures and instructions. Multivariate analysis revealed five predictors of satisfaction: treatment outcome (OR, 2.14), individualized medical care (OR, 1.64), clear reply to patient's inquiries by physicians (OR, 1.63), kindness of nonmedical professionals (OR, 3.01), and room amenities (OR, 2.02). No association between demographic data and overall satisfaction was observed. CONCLUSION: Five key determinants that can be addressed by health-care providers in order to improve patient satisfaction were identified. Our findings highlight the importance of the communicational behavior of health-care professionals and the transparency of discharge management. PMID- 26545603 TI - Left ventricular end diastolic pressure for detection of intracoronary ergonovine induced myocardial ischemia. AB - BACKGROUND: Recent consensus on variant angina defines significant spasm as total or subtotal occlusion of a coronary artery. However, the clinical significance of "less-than-subtotal" spasm needs to be reappraised, especially if the coronary spasm is combined with chest pain. Therefore, we evaluated the feasibility of left ventricular end diastolic pressure (LVEDP) as a tool to detect myocardial ischemia during ergonovine provocation testing. METHODS: After achieving two access sites, 29 patients underwent successful LVEDP monitoring using 5-Fr pigtail catheters during ergonovine provocation tests. Patients were divided into two groups based on the occurrence of anginal symptoms. RESULTS: Of the 29 patients, 16 (55 %) patients had anginal symptoms. LVEDP was significantly increased in the symptomatic group compared with the nonsymptomatic group (?LVEDP 5.6 +/- 4.2 vs. 1.2 +/- 2.0 mmHg, p = 0.002). However, of the 16 patients with anginal symptoms, positive provocation test results were confirmed in only six patients (38 %) as per the traditional standard (> 90 % inducible spasm of the epicardial coronary artery). CONCLUSION: Compared with the traditional standard, LVEDP may have advantages in terms of elucidating anginal symptoms in patients suspected of having coronary vasospasm when performing ergonovine provocation tests. PMID- 26545604 TI - [ESC guidelines 2015. Non-ST-elevation acute coronary syndrome]. AB - In August 2015 the European Society of Cardiology (ESC) published new guidelines for the management of acute coronary syndrome in patients presenting without persistent ST-segment elevation, which incorporate the scientific progress since 2011. The innovation with probably the most impact on the clinical practice is the introduction of 0 h/1 h protocols for exclusion or inclusion of myocardial infarction without ST-segment elevation. These 0 h/1 h protocols are equally recommended to the established 0 h/3 h protocol. For these protocols blood is drawn on admission and 1 h later and the troponin level is analyzed by means of highly sensitive troponin assays. Troponin cut-off values were validated in several large studies, therefore, now facilitating a faster exclusion of myocardial infarction with an equal negative predictive value to 3 h protocols. Additionally, access via the radial artery is recommended over a femoral artery access for coronary angiography and when necessary the subsequent coronary intervention. Other novel aspects apply to the anti-ischemic and anti-thrombotic medication. PMID- 26545605 TI - Formulation and comparative evaluation of HPMC and water soluble chitosan-based sparfloxacin nanosuspension for ophthalmic delivery. AB - Ophthalmic nanosuspensions (ONS) have shown a potential for ophthalmic delivery over the conventional ocular formulations. The objective of the study was to assess the effect of surfactants and polymers on particle size and drug release. Sparfloxacin ONS were prepared by optimizing the concentration of HPMC E5 and water soluble chitosan by using solvent diffusion method followed by probe sonication. The Poloxamer 407 and Kolliphor P188 were used as a surfactant. The produced nanosuspensions were characterized for particle size, shape, zeta potential and drug release. The average particle size of the nanosuspension was 300 to 500 nm. The in vitro drug release study showed that the optimized nanosuspension of water soluble chitosan sustained drug release up to 9 h compared to 6 h for the hydroxypropylmethylcellulose (HPMC) nanosuspension. Further, the sparfloxacin ONS formulation showed excellent ocular tolerance and biocompatibility as determined by hen's egg test chorioallantoic membrane (HET CAM) and resazurin assay on Vero cell lines. Moreover, optimized formulation was found to be stable, isotonic, non-toxic with higher in vitro and in vivo antimicrobial potential. PMID- 26545606 TI - Completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas: report of six cases and a review of the literature. AB - PURPOSE: There are no accepted surgical strategies for the treatment of pancreatic cancer recurrence in the remnant pancreas after initial resection. We retrospectively analyzed our experiences with patients undergoing completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas. METHODS: Six patients with recurrent pancreatic cancer in the remnant pancreas underwent completion pancreatectomy between March 2005 and December 2012. Operative, postoperative, and pathological data and long-term outcomes for these six patients were analyzed retrospectively. RESULTS: There was no operative morbidity or mortality associated with completion pancreatectomy. The median survival times were 49.0 and 27.5 months after initial resection and second pancreatectomy, respectively. However, all six patients died during follow-up. Five patients had recurrent pancreatic cancer at the time of death. One patient had no recurrence but had poor blood sugar control and eventually died after repeated bouts of cholangitis. CONCLUSIONS: Completion pancreatectomy is a safe and effective option in select patients with local pancreatic cancer recurrence in the remnant pancreas after initial pancreatectomy. It is essential to select patients who have a good performance status and can tolerate major surgery and the resultant apancreatic state. PMID- 26545607 TI - Effect of perioperative dexamethasone on subjective voice quality after thyroidectomy: a meta-analysis and systematic review. AB - BACKGROUND: Prophylactic dexamethasone has been shown to reduce postoperative pain, nausea, and vomiting in patients undergoing thyroidectomy. However, its effects on postoperative voice outcomes remain uncertain. METHODS: A systematic review and meta-analysis of the literature was conducted. Cochrane database, MEDLINE, EMBASE, and CINAHL were thoroughly searched. Studies that compared intravenous dexamethasone administration with no dexamethasone in patients undergoing thyroidectomy were included. Main outcome measure was the difference in postoperative voice assessment between groups. Standardized mean difference (SMD) and 95 % confidence intervals (CIs) were estimated using fixed and random effects models. RESULTS: Four studies with a total of 313 patients met inclusion criteria. Significant heterogeneity of study results was noted. Using random effects models, pooled data showed no difference in subjective voice quality between groups preoperatively (SMD, 0.29; 95 % CI -0.37 to 0.96; P = 0.39), 24 h after thyroidectomy (SMD, -1.02; 95 % CI -2.36 to 0.31; P = 0.13), or at 48 h (SMD, -0.05; 95 % CI -0.30 to 0.21; P = 0.72). A sensitivity analysis excluding one observational study yielded similar results. CONCLUSION: There are insufficient data for definite conclusions to be drawn regarding the effectiveness of a single perioperative administration of dexamethasone to reduce short-term voice disturbances after thyroidectomy. Further prospective trials using objective voice analysis are warranted to evaluate the efficacy of dexamethasone. PMID- 26545609 TI - Thylakoid membrane function in heterocysts. AB - Multicellular cyanobacteria form different cell types in response to environmental stimuli. Under nitrogen limiting conditions a fraction of the vegetative cells in the filament differentiate into heterocysts. Heterocysts are specialized in atmospheric nitrogen fixation and differentiation involves drastic morphological changes on the cellular level, such as reorganization of the thylakoid membranes and differential expression of thylakoid membrane proteins. Heterocysts uphold a microoxic environment to avoid inactivation of nitrogenase by developing an extra polysaccharide layer that limits air diffusion into the heterocyst and by upregulating heterocyst-specific respiratory enzymes. In this review article, we summarize what is known about the thylakoid membrane in heterocysts and compare its function with that of the vegetative cells. We emphasize the role of photosynthetic electron transport in providing the required amounts of ATP and reductants to the nitrogenase enzyme. In the light of recent high-throughput proteomic and transcriptomic data, as well as recently discovered electron transfer pathways in cyanobacteria, our aim is to broaden current views of the bioenergetics of heterocysts. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. PMID- 26545610 TI - Distribution and dynamics of OXPHOS complexes in the bacterial cytoplasmic membrane. AB - Oxidative phosphorylation (OXPHOS) is an essential process for most living organisms mostly sustained by protein complexes embedded in the cell membrane. In order to thrive, cells need to quickly respond to changes in the metabolic demand or in their environment. An overview of the strategies that can be employed by bacterial cells to adjust the OXPHOS outcome is provided. Regulation at the level of gene expression can only provide a means to adjust the OXPHOS outcome to long term trends in the environment. In addition, the actual view is that bioenergetic membranes are highly compartmentalized structures. This review discusses what is known about the spatial organization of OXPHOS complexes and the timescales at which they occur. As exemplified with the commensal gut bacterium Escherichia coli, three levels of spatial organization are at play: supercomplexes, membrane microdomains and polar assemblies. This review provides a particular focus on whether dynamic spatial organization can fine-tune the OXPHOS through the definition of specialized functional membrane microdomains. Putative mechanisms responsible for spatio-temporal regulation of the OXPHOS complexes are discussed. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. PMID- 26545608 TI - CYP1A1 and GSTP1 gene variations in breast cancer: a systematic review and case control study. AB - In first part of this study, a systematic review was designed to explore the involvement of CYP1A1 and GSTP1 genes in breast cancerogenesis. Based on systematic review, we designed a study to screen CYP1A1 and GSTP1 genes for mutation and their possible association with breast carcinogenesis. A total of 400 individuals were collected and analyzed by PCR-SSCP. After sequence analysis of coding region of CYP1A1 we identified eleven mutations in different exons of respective gene. Among these eleven mutations, ~3 folds increased breast cancer risk was found associated with Asp82Glu mutation (OR 2.99; 95% CI 1.26-7.09), with Ser83Thr mutation (OR 2.99; 95% CI 1.26-7.09) and with Glu86Ala mutation (OR 3.18; 95% CI 1.27-7.93) in cancer patients compared to controls. Furthermore, ~4 folds increase in breast cancer risk was found associated with Asp347Glu, Phe398Tyr and 5178delT mutations (OR 3.92; 95% CI 1.35-11.3) in patients compared to controls. The sequence analysis of GSTP1 resulted in identification of total five mutations. Among these five mutations, ~3 folds increase in breast cancer risk was observed associated with 1860G>A mutation, with 1861 1876delCAGCCCTCTGGAGTGG mutation (OR 2.70; 95% CI 1.10-6.62) and with 1861C>A mutation (OR 2.97; 95% CI 1.01-8.45) in cancer patients compared to controls. Furthermore, ~5 folds increase in breast cancer risk was associated with 1883G>T mutation (OR 4.75; 95% CI 1.46-15.3) and ~6 folds increase in breast cancer risk was found associated with Iso105Val mutation (OR 6.43; 95% CI 1.41-29.3) in cancer patients compared to controls. Our finding, based on systematic review and experimental data suggest that the polymorphic CYP1A1 and GSTP1 genes may contribute to risk of developing breast cancer. PMID- 26545611 TI - Metastatic Sarcomatoid Carcinoma of the Small Intestine: a Case Report of Rare Tumor with Literature Review. PMID- 26545612 TI - Treatment of Pancreatic Adenocarcinoma in Elderly Patients over 75 Years of Age: A Retrospective Series of 129 Patients. AB - PURPOSE: To better know the presentation and outcome of pancreatic adenocarcinoma in patients above 75 years of age. METHOD: Retrospective analysis of consecutive patients with a pancreatic adenocarcinoma seen in the Comprehensive Cancer Center of Marseille between January 2002 and January 2012 was used. RESULTS: During these 10 years, 129 patients older than 75 years of age were seen, 61 females and 68 males, median age 78. At diagnosis, the tumor was metastatic in 45%. First line treatments were: surgical resection in 22 cases, radio-chemotherapy in 20 cases (1 operated on later), systemic chemotherapy in 59 cases, and best supportive care alone in 28 cases. Resection was possible in 19 cases and was R0 in 17; post-operative mortality was 0%, and half received adjuvant chemotherapy. Median overall survival was 43 months with a 2-year overall survival of 64%. For locally advanced tumor, 16 received best supportive care and 33 a specific treatment (20 cases of radio-chemotherapy). Median overall survival was 9.1 months and 2-year overall, survival was 6.1%. Among the 58 metastatic patients, 79% received systemic chemotherapy (most by gemcitabine); tolerance was correct in half. Median overall survival was 4.7 months, with a 2-year overall survival of 5.3%. CONCLUSIONS: Surgery of pancreatic adenocarcinoma is feasible and safe in elderly patients with good outcomes. In advanced and metastatic patients, the outcome is poor despite a correct tolerance of systemic chemotherapy. Randomized trials specially designed for this population are urgently needed. PMID- 26545613 TI - Unipolar and bipolar patient responses to a new scale measuring the consequences of depression. AB - There are generic measures available to assess functional impairment associated with clinical conditions, but no measure has been developed to specifically evaluate consequences of differing mood disorders, our current objective. In this study, 208 participants took part in a research interview which aimed to differentiate clinical depression from non-clinical mood states. The 126 participants who met diagnostic criteria for clinical depression (i.e., bipolar disorder, melancholic depression or non-melancholic depression) were asked to judge whether they had experienced any of 24 consequences of their depressive episodes with the measure focusing on occupational, personal and interpersonal functioning. Such consequences were affirmed by 100% of participants diagnosed with bipolar disorder, 84% of those experiencing melancholic depression and 74% of those who had experienced a non-melancholic depressive episode. Results from a three-factor solution were consistent with the expected domains (i.e. work and relationships; self-care and daily functioning; intimate relationships and coping), and had sound goodness of fit properties. Participants with bipolar disorder were more likely to affirm each item compared to participants with unipolar depression, and participants with melancholic depression affirmed each item at a higher rate than participants who had experienced non-melancholic episodes. The new measure (the Consequences of Depression Scale; CODS) could be utilised in research and clinical activities seeking to identify and quantify the personal and economic burden of mood disorders, and provides an additional perspective for evaluating the impact of mood disorders on interpersonal, personal and occupational functioning. PMID- 26545614 TI - Therapists' and patients' stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: A preliminary observational study. AB - Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice. PMID- 26545615 TI - CD73 on B16F10 melanoma cells in CD73-deficient mice promotes tumor growth, angiogenesis, neovascularization, macrophage infiltration and metastasis. AB - Ecto-5'-nucleotidase (CD73), an enzyme providing interstitial adenosine, mediates diverse physiological and pathological responses. In tumor progression, it has primarily an immunosuppressive role but is also thought to regulate neovascularization. However, the latter role is still in debate. When B16F10 melanoma was subcutaneously injected into CD73 knockout mice, changes in the tumor vasculature were not always observed. However, we demonstrated earlier that the growth and vascularization of B16F10 melanoma in CD73 knockout mice depend on the low presence of CD73 on tumor cells. To further analyze the role of CD73 on tumor growth and vascularization, we compared the changes in B16F10 melanoma subcutaneously injected into right flank of wild-type mice, CD73 knockout mice lacking host CD73 only, and CD73 knockout mice with tumor cell CD73 either inhibited with AOPCP (adenosine alpha,beta-methylene 5'-diphosphate) or permanently knocked down through genetic modification. We report here that both inhibition and knockdown of tumor CD73 further inhibited tumor growth compared to host CD73 knockout alone. MAP-kinase signaling pathway activation also decreased more strongly in the stable knockdown. There was a significant reduction in the angiogenic activation of blood microvessels as observed by decreased anti-VEGFR2 staining. Stable CD73 knockdown also reduced endothelial cell proliferation as measured by anti-CD105 staining. However, only chemical inhibition with AOPCP significantly augmented the reduction in intratumoral microvessel density induced by host CD73 knockout. Such reduction was not observed when tumor CD73 was knocked down due to the much slower tumor growth and decreased oxygen demand as indicated by the low expression of Bad, a hypoxia marker. Decreased CD73 activity also led to the decreased expression of angiogenic factors, including VEGF and bFGF that was only partially reversed by hypoxia in tumors treated with AOPCP. Both inhibition and knockdown of tumor CD73 significantly decreased tumor macrophage infiltration and induced microenvironment changes, thereby influencing MI or MII macrophage polarization. Additionally, tumor cell CD73 is important in metastasis formation through adenosine-independent attachment to endothelium. We conclude that even low tumor cell CD73 expression has an undeniable role in melanoma progression, including the regulation of many aspects of angiogenesis. CD73 is thus a viable target in anti-angiogenic melanoma therapy. PMID- 26545616 TI - Acute surgical management of traumatic knee dislocations--Average follow-up of 10 years. AB - BACKGROUND: Traumatic knee dislocations have been managed historically by means of either delayed reconstruction or non-operative methods. More recently, there has been a trend towards early reconstruction. There is no clear consensus in the literature as to how such patients should be managed and in what time frame. OBJECTIVE: The aim of this study was to establish the long-term outcome of patients who underwent acute surgical management of their traumatic knee dislocation. METHODS: Thirty-six patients with traumatic knee dislocations were treated by multi-ligament reconstruction. All surgical interventions occurred within 21 days of presentation. The collateral ligament complexes were primarily repaired where possible and reconstructions were performed with either autograft, allograft or the ligament augmentation and reconstruction system (LARS) synthetic graft. RESULTS: The mean time to surgery was 12 days (1 to 21) with a mean follow up of 10.1 years (7 to 19). The International Knee Documentation Committee (IKDC) assessment demonstrates that 56% of patients went on to have "nearly normal" knee function and the average Tegner-Lysholm score of 80 (57 to 91), is consistent with good function. The Knee Outcome score (KOS) was 84% for Activities of Daily Living and 74% for Sports. CONCLUSION: This study demonstrates a high level of overall knee function following the acute surgical reconstruction of traumatic knee dislocations. LEVEL OF EVIDENCE: Level 2B: Cohort Study with Outcome Measures. PMID- 26545617 TI - Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. AB - Exosomes, which are expected to be delivery systems for biomolecules such as nucleic acids, are collected by several methods. However, the effect of exosome isolation methods on the characteristics of exosomes as drug carriers, such as recovery efficiency after sterile filtration and pharmacokinetics, has not been investigated despite the importance of these characteristics for the development of exosome-based delivery systems. In the present study, exosomes collected from murine melanoma B16-BL6 cells by several methods were compared with respect to dispersibility, recovery rate after filtering, and clearance from the blood circulation in mice. The exosomes were collected by three ultracentrifugation based methods: simple ultracentrifugation/pelleting (pelleting method), ultracentrifugation with an iodixanol cushion (cushion method), and ultracentrifugation on an iodixanol density gradient (gradient method). The isolation methods had little effect on the particle number of exosomes. In contrast, transmission electron microscopy observation and size distribution measurement using tunable resistive pulse sensing indicated that the exosomes of the gradient method were more dispersed than the others. The exosomes were labeled with Gaussia luciferase and intravenously injected into mice. Clearance of injected exosomes from the blood circulation did not significantly change with isolation methods. When the exosomes were filtered using a 0.2-MUm filter, the recovery rate was 82% for the exosomes of the gradient method, whereas it was less than 50% for the others. These results indicate that the exosome isolation method markedly affects the dispersibility and filtration efficiency of the exosomes. PMID- 26545618 TI - Opponent Coding of Sound Location (Azimuth) in Planum Temporale is Robust to Sound-Level Variations. AB - Coding of sound location in auditory cortex (AC) is only partially understood. Recent electrophysiological research suggests that neurons in mammalian auditory cortex are characterized by broad spatial tuning and a preference for the contralateral hemifield, that is, a nonuniform sampling of sound azimuth. Additionally, spatial selectivity decreases with increasing sound intensity. To accommodate these findings, it has been proposed that sound location is encoded by the integrated activity of neuronal populations with opposite hemifield tuning ("opponent channel model"). In this study, we investigated the validity of such a model in human AC with functional magnetic resonance imaging (fMRI) and a phase encoding paradigm employing binaural stimuli recorded individually for each participant. In all subjects, we observed preferential fMRI responses to contralateral azimuth positions. Additionally, in most AC locations, spatial tuning was broad and not level invariant. We derived an opponent channel model of the fMRI responses by subtracting the activity of contralaterally tuned regions in bilateral planum temporale. This resulted in accurate decoding of sound azimuth location, which was unaffected by changes in sound level. Our data thus support opponent channel coding as a neural mechanism for representing acoustic azimuth in human AC. PMID- 26545619 TI - Single-compound and cumulative risk assessment of mycotoxins present in breakfast cereals consumed by children from Lisbon region, Portugal. AB - Humans can be exposed to multiple chemicals, but current risk assessment is usually carried out on one chemical at a time. Mycotoxins are commonly found in a variety of foods including those intended to consumption by children namely breakfast cereals. The present study aims to perform, the risk assessment of single and multiple mycotoxins present in breakfast cereals consumed by children (1-3 years old) from Lisbon region, Portugal. Daily exposure of children to ochratoxin A, fumonisins and trichothecenes showed no health risks to the children population considering individual mycotoxins, while exposure to aflatoxin B1 (AFB1) suggested a potential health concern for the high percentiles of intake (P90, P95 and P99). The combined exposure to fumonisins and trichothecenes are not expected to be of health concern. The combined margin of exposure (MoET) for the aflatoxins group could constitute a potential health concern and AFB1 was the main contributor for MoET. Legal limits and control strategies regarding the presence of multiple mycotoxins in foodstuffs is an urgent need. To the best of our knowledge, this is the first time a cumulative risk assessment was performed on multiple mycotoxins present in breakfast cereals consumed by children. PMID- 26545620 TI - Functional characterization of multiple DICER1 mutations in an adolescent. PMID- 26545621 TI - Secondhand smoke and incidence of dental caries in deciduous teeth among children in Japan: population based retrospective cohort study. PMID- 26545622 TI - Absence or presence? Complexities in the donor narratives of single mothers using sperm donation. AB - STUDY QUESTION: How do single mothers who have conceived a child via anonymous or identity-release sperm donation represent the donor? SUMMARY ANSWER: While the majority of mothers described their anonymous and identity-release donors as symbolically significant to their families, others were more likely to emphasize that their lack of information limited their thoughts about him. WHAT IS KNOWN ALREADY: There is limited understanding of the factors that impact upon how single mothers represent the donor, and whether or not they are determined by specific donor programmes (anonymous or identity-release). STUDY DESIGN, SIZE, DURATION: Qualitative interviews were conducted with 46 women who had treatment at a UK licensed fertility clinic during the years 2003-2009. Twenty mothers (43%) had used an anonymous donor, and 26 (57%) had used an identity-release donor. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 46 mothers interviewed, all had at least one child conceived via donor insemination who was between the ages of 4 and 9 years. Mothers were heterosexual and were currently without a live-in and/or long-term partner. Interview data were analysed qualitatively according to the principles of thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Findings indicated marked diversity in single mothers' representations of the donor. Most (n = 27) mothers talked about the donor as symbolically significant to family life and were likely to describe the donor as (i) a gift-giver, (ii) a gene-giver and (iii) a potential partner. Others (n = 16) talked about the donor as (i) unknown, (ii) part of a process and (iii) out of sight and out of mind. There were mothers with anonymous and identity-release donors in each group. Several mothers explained that their feelings about the donor had changed over time. LIMITATIONS, REASONS FOR CAUTION: All mothers conceived at a licensed fertility clinic in the UK. Findings are limited to individuals willing and able to take part in research on donor conception. WIDER IMPLICATIONS OF THE FINDINGS: The study offers greater insight into the factors influencing the donor narratives produced in single-mother families. It has implications for the counselling and treatment of single women seeking fertility treatment with donor gametes in both anonymous and identity-release programmes. Given that the number of clinics offering identity-release programmes worldwide seems to be increasing, the finding that single women may have varying preferences with regard to donor type, and varying interest levels with regard to donor information, is important. It is recommended that clinicians and other fertility clinic staff guard against making assumptions about such preferences and any thoughts and feelings about the donor or donor information on the basis of marital status. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Wellcome Trust [097857/Z/11/Z]. The authors have no conflicts of interest to declare. PMID- 26545623 TI - Mitral Valve Surgery in Patients With Severe Mitral Annular Calcification. AB - BACKGROUND: Mitral valve surgery in patients with severe mitral annular calcification can be challenging. We investigated surgical outcomes of mitral valve surgery with complete annular decalcification and reconstruction. METHODS: Between January 2004 and December 2013, 2,104 patients underwent mitral valve surgery at our institution. Of these, 61 patients (mean age 70 years) with severe mitral annular calcification were reviewed. Valve lesions were stenosis in 20 patients (32.8%), regurgitation in 16 (26.2%), mixed in 19 (31.1%), and prosthetic valve dehiscence in 6 (9.8%). Calcified annulus was resected completely and reconstructed with equine pericardium in 48 patients (78.7%), autologous pericardium in 10 (16.4%), and polytetrafluoroethylene felt pledgets in 3 (4.9%). Mitral valve repair was attempted in 4 patients (6.6%) and mitral valve replacement in 57 (93.4%). One patient (1.6%) had conversion from repair to replacement due to cardiac rupture. Concomitant procedures included aortic valve replacement in 36 patients (56.3%), tricuspid valve surgery in 28 (43.8%), and coronary artery bypass graft surgery in 18 (28.1%). Mean follow-up was 3.5 +/- 2.5 years. RESULTS: There was no 30-day hospital death. Early complications were left ventricular pseudoaneurysm in 1 patient, pericardial patch dehiscence in 1, severe arrhythmia in 6, and stroke in 2. At 5 years, rates of survival and freedom from cardiac death and major adverse valve-related events were 75.6%, 79.7%, and 72.7%, respectively. Multivariate analysis indicated coronary artery disease as an independent predictor of cardiac death. CONCLUSIONS: In patients with severe mitral annular calcification undergoing mitral valve surgery, complete annular decalcification and reconstruction yields favorable outcomes. PMID- 26545624 TI - Beyond the Aortic Root: Staged Open and Endovascular Repair of Arch and Descending Aorta in Patients With Connective Tissue Disorders. AB - BACKGROUND: Improvements in care have prolonged survival of patients with connective tissue disorders (CTDs), but their entire native aorta remains at risk. Little data are available to guide treatment. Objectives were to characterize patients, describe repair methods, and assess outcomes. METHODS: From 1996 to 2012, 527 patients with CTDs underwent cardiovascular operations. Beyond the root, arch and descending repair was performed in 121 patients (23%) for aneurysm (n = 17), acute complicated dissection (n= 5), or chronic dissection with aneurysmal degeneration (n = 99). CTD diagnoses included Marfan (n = 107), marfanoid (n = 7), Ehlers-Danlos (n = 4), and Loeys-Dietz (n = 3) syndromes. Eighty-seven (72%) had a previous ascending aorta repair, including 51 (57%) for type A dissection. Median interval to distal operation was 8.4 years. Index procedures for repair beyond the root were elephant trunk (ET) stage I (n = 63), open descending repair (n = 26), thoracoabdominal repair (n = 13), total arch replacement (n = 13), and stent-grafting (n = 6: frozen ET 3, thoracic endovascular aortic repair [TEVAR] 3). Median follow-up was 4.4 years. RESULTS: Operative mortality was 2.5% (3 of 121). No paralysis occurred, but 3 patients (2.5%) had nonpermanent stroke, 4 (3.3%) required dialysis, 12 (10%) required tracheostomy, and 13 (11%) underwent reoperation for bleeding. During follow-up, 67 patients underwent 85 additional distal aortic procedures (58 open, 27 endovascular, 49 of which were stage II ET). By 10 years, probability of at least 1 reintervention was 61%. At 1, 5, and 10 years, estimated survival was 91%, 79%, and 62%, and event-free survival was 52%, 35%, and 24%, respectively. CONCLUSIONS: Most patients with CTDs who require operations beyond the aortic root have aortic dissection and require multiple reinterventions. Staged repair strategies, including open repair in combination with TEVAR, are feasible, and benefits outweigh risks. These patients require lifelong imaging surveillance. PMID- 26545625 TI - Endoscopic Mediastinal Staging in Lung Cancer Is Superior to "Gold Standard" Surgical Staging. AB - BACKGROUND: The objective was to evaluate whether endobronchial ultrasonography (EBUS) or endoscopic ultrasonography (EUS) staging techniques of the mediastinum for lung cancer can change the treatment plan compared with the "gold standard" of surgical staging. METHODS: Patients were retrospectively identified from a prospectively collected database. Endoscopic staging was compared with the "gold standard" cervical mediastinoscopy (CM). In cases where mediastinoscopy was not performed, EBUS/EUS was compared with "ideal" CM, a virtual procedure, which was assumed to have 100% rates of sensitivity and specificity. RESULTS: EBUS was performed in 324 patients (99%), EUS in 295 patients (90%), and CM in 101 patients (31%); 226 patients (69%) were assumed to have undergone a virtual ideal CM and a virtual surgical mediastinal staging; 108 positive biopsies (33.0%) with endosonography had sampling of targets that were out of the scope of CM. Distant metastatic disease was diagnosed by EBUS/EUS in 7 patients (2.1%); 22 patients (6.7%) had positive targets outside the reach of the CM or virtual CM. If the 14 patients who had positive stations 5, 6, 10, and 11 are excluded (accessible with anterior mediastinotomy or extended cervical mediastinoscopy), there were 6 patients (1.8%) in whom endosonography upstaged the patient over ideal surgical mediastinal staging. In 20 patients (6.1%), ultrasound-guided biopsy made the diagnoses, which changed the treatment plan over CM and ideal CM. CONCLUSIONS: Combined EBUS- and EUS-guided biopsies can access more targets, including lung and distant metastasis, and thus have the potential to upstage patients compared with mediastinoscopy and change the treatment plan. PMID- 26545626 TI - Lipoproteins as modulators of atherothrombosis: From endothelial function to primary and secondary coagulation. AB - Atherothrombosis is a complication of atherosclerosis that causes acute cardiovascular events such as myocardial infarction and stroke. Circulating lipid levels are highly correlated with atherosclerotic plaque development. In addition, experimental evidence suggests that lipids also directly influence thrombosis and influence the risk and the outcome of acute cardiovascular events. Plasma lipoproteins influence three aspects important to atherothrombosis: endothelial function, platelet aggregation (primary coagulation) and secondary coagulation. Overall, VLDL, LDL and oxLDL promote thrombus formation, whereas HDL shows antithrombotic actions. In this review we will address the current knowledge about modulation of atherothrombosis by lipoproteins, summarizing findings from in vitro and in vivo animal studies, as well as from observational and interventional studies in humans. We will conclude with future perspectives for lipid modulation in the prevention of atherothrombosis. PMID- 26545627 TI - The ERK1/2 pathway participates in the upregulation of the expression of mesenteric artery alpha1 receptors by intravenous tail injections of mmLDL in mice. AB - Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular diseases. However, no studies examining the effect of mmLDL on vascular smooth muscle receptors have been released. The current study investigated the effect of mmLDL on the mesenteric artery alpha1 adrenoceptor and the molecular mechanisms. Mice were divided into the normal saline (NS), mmLDL, and mmLDL+U0126 groups. In the mmLDL+U0126 group, the animals were subjected to an intravenous tail injection of mmLDL and an intraperitoneal injection of U0126. Vascular tension caused by noradrenaline (NA) in mesenteric arteries was measured with a sensitive myograph system. The serum levels of oxLDL, TNF-alpha, and IL 1beta were detected using enzyme-linked immunosorbent assays. The expressions of the alpha1 adrenoceptor, the alpha2 adrenoceptor, TNF-alpha, IL-1beta, and pERK1/2 were detected using real-time polymerase chain reactions and Western blot analysis. Compared with the NS group, the mmLDL group exhibited a noticeably enhanced NA shrinkage dose-response curve and a significantly increased Emax value (P<0.01). Prazosin (alpha1 adrenoceptor antagonist) caused a noticeable right shift of the dose-response curve. U0126 inhibited the increases in the serum levels and vessel wall expression of IL-1beta and TNF-alpha and enhanced the NA shrinkage dose-response curve caused by mmLDL, as observed by a significantly decreased Emax value (P<0.01). It inhibited the increased alpha1 adrenoceptor expression caused by mmLDL. The serum levels of IL-1beta and TNF alpha demonstrated a positive correlation with the NA-induced maximum shrinkage percentage. U0126 inhibited the mmLDL-induced increase in the pERK1/2 protein level in the vessel wall. In conclusion, mmLDL increased the serum levels of IL 1beta and TNF-alpha in vivo by activating the ERK1/2 pathway, which resulted in alpha1 receptor-mediated vasoconstriction and an increase in the expression of alpha1 adrenoceptor. The results of this study may provide new ideas for the prevention and cure of cardiovascular diseases in the future. PMID- 26545628 TI - Chemerin in renal dysfunction and cardiovascular disease. AB - The potential involvement of chemerin in cardiovascular and renal dysfunction has recently been acknowledged. There are indeed many links between this protein and inflammation, atherosclerosis, and multiple obesity- and diabetes-related parameters such as body mass index, insulin resistance, and blood levels of insulin, cholesterol, triglycerides, and glucose. In addition, in the last few years, several reports have investigated the circulating chemerin levels and their pathophysiologic significance in chronic kidney disease populations. However, there are still gaps in our understanding of this matter, in particular as to whether elevated chemerin might be the cause behind, or simply mirror, a reduced renal function. The limitations of the present knowledge on chemerin may partly relate to the lack of specific antibodies for assessing the different active isoforms of the protein. Measuring its bioactive serum concentration, and achieving a precise overall pattern of the tissue-specific formation of different isoforms, with the use of suitable technology, will ultimately help define the role of chemerin in disease pathophysiology, or as a diagnostic or therapeutic marker. PMID- 26545629 TI - Gray and white matter structural changes in corticobasal syndrome. AB - We investigated gray matter and white matter (WM) changes in corticobasal syndrome (CBS). T1-weighted and diffusion tensor images (3T-magnet) were obtained in 11 patients and 11 healthy subjects (HS). Magnetic resonance imaging data were analyzed using FreeSurfer and Tracts Constrained by Underlying Anatomy to evaluate cortical thickness (CTh), surface area, and subcortical volumes as well as diffusion tensor image parameters along the major WM tracts. Compared with HS, the whole patient group showed decreased CTh in the prefrontal cortex, precentral gyrus, supplementary motor area, insula, and temporal pole bilaterally. When we divided patients into 2 subgroups (left: L-CBS, right: R-CBS) on the basis of the clinically more affected upper limb, the most prominent decrease in CTh occurred in the hemisphere contralateral to the more affected side. The whole patient group also had volume loss in the putamen, hippocampus, and accumbens bilaterally, in the corpus callosum and right amygdala. Finally, we found diffusion changes in several WM tracts with axial diffusivity being altered more than radial diffusivity. The upper limb motor severity negatively correlated with the contralateral CTh in the precentral and/or postcentral gyri and contralateral volumes of putamen and accumbens. The CTh asymmetry in postcentral and/or paracentral gyri also negatively correlated with disease duration. Cortical thinning, volume loss, and fiber tract degeneration in specific brain regions are important pathophysiological abnormalities in CBS. PMID- 26545630 TI - A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin. AB - Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 * 10(-7)) and interleukin 6 (IL6, p = 9.94 * 10(-6), in the entire data set and in the APOE epsilon4- individuals p = 7.40 * 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. PMID- 26545632 TI - A novel histone deacetylase 1 and 2 isoform-specific inhibitor alleviates experimental Parkinson's disease. AB - With increased histone deacetylase (HDAC) activity and histone hypoacetylation being implicated in neurodegeneration, HDAC inhibitors have been reported to have considerable therapeutic potential. Yet, existing inhibitors lack specificity and may show substantial adverse effect. In this study, we identified a novel HDAC1/2 isoform-specific inhibitor, K560, with protective effects against 1-methyl-4 phenylpyridinium (MPP(+))- and/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal death in both in vitro and in vivo Parkinson's disease model. K560 attenuated cell death induced by MPP(+) in differentiated SH-SY5Y cells through the sustained expression of an antiapoptotic protein, X-linked inhibitor of apoptosis (XIAP). Inhibition of XIAP expression by locked nucleic acid antisense oligonucleotides abolished the protective effect of K560. Inactivation of mitogen-activated protein kinase cascades, reduced p53 phosphorylation, and down-regulation of p53-upregulated modulator of apoptosis on K560 treatment were also observed. Furthermore, pre- and post-oral administration of K560 to mice prevented MPTP-induced loss of dopaminergic neurons in substantia nigra, suggesting that selective inhibition of HDAC1 and HDAC2 by K560 may pave the way to new strategies for Parkinson's disease treatment. PMID- 26545631 TI - MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials. AB - The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort. PMID- 26545633 TI - Electroencephalogram slowing predicts neurodegeneration in rapid eye movement sleep behavior disorder. AB - A large proportion of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) develop a synucleinopathy, mostly Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Therefore, identifying markers of neurodegeneration in iRBD could have major implications. We aimed to assess the usefulness of electroencephalography (EEG) spectral analysis performed during wakefulness for predicting the development of a neurodegenerative disease in iRBD. Fifty-four iRBD patients, 28 of whom developed Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies (mean follow-up: 3.5 years), and 30 healthy controls underwent at baseline a resting-state waking EEG recording, neurological exam, and neuropsychological assessment. Absolute and relative spectral powers were analyzed for 5 frequency bands in frontal, central, parietal, temporal, and occipital regions. The slow-to-fast [(delta + theta)/(beta1 + beta2)] power ratio for each of the 5 cortical regions and the dominant occipital frequency were calculated as an index of cortical slowing. Patients who developed disease showed higher absolute delta and theta power in all 5 cortical regions compared to disease-free patients and controls. The slow to-fast power ratio was higher in all regions in patients who developed disease than in the 2 other groups. Moreover, patients who developed disease had a slower dominant occipital frequency compared to controls. The only significant difference observed between disease-free iRBD patients and controls was higher absolute delta power in frontal and occipital regions in iRBD patients. Specific EEG abnormalities were identified during wakefulness in iRBD patients who later developed a synucleinopathy. EEG slowing is a promising marker of neurodegeneration in iRBD patients. PMID- 26545634 TI - Relationship between sleep-disordered breathing and metabolic syndrome after adjustment with cardiovascular risk factors. AB - AIMS: It is important to identify the risk factors for metabolic syndrome (MetS) in order to prevent the development of cardio-/cerebrovascular diseases. The authors estimated the risk factors for the development of MetS with special emphasis on the severity of sleep-disordered breathing (SDB). METHODS: We conducted as a cross-sectional study in subjects undergoing intensive health examination (581 men aged 33-84 years). Diagnosis of MetS was based on the criteria of the National Cholesterol Education Program Expert Panel. RESULTS: The prevalence of MetS in subjects with severe SDB, which was defined as an apnea hypopnea index (AHI) of 30 or higher, was 40.7%, which was significantly higher than that in the subjects without severe SDB (29.3%). The odds ratio (OR) (95% confidence interval [CI]) of the logarithmic-transformed AHI for MetS was 1.6 (1.1-2.4) after adjustments for age, serum uric acid, logarithmic-transformed serum C-reactive protein, smoking history, exercise history and alcohol history. When the subjects were categorized by the severity of SDB, the OR (95% CI) of severe SDB, which was the only category that showed significant association, was 2.2 (1.2-4.0). CONCLUSION: A significant association was observed between severe SDB and the presence of MetS in the subjects (all male) of this study. PMID- 26545635 TI - Clinical Characteristics and Outcomes of Renal Infarction. AB - BACKGROUND: Renal infarction is a rare condition resulting from an acute disruption of renal blood flow, and the cause and outcome of renal infarction are not well established. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 438 patients with renal infarction in January 1993 to December 2013 at 9 hospitals in Korea were included. Renal infarction was defined by radiologic findings that included single or multiple wedge-shaped parenchymal perfusion defects in the kidney. PREDICTOR: Causes of renal infarction included cardiogenic (n=244 [55.7%]), renal artery injury (n=33 [7.5%]), hypercoagulable (n=29 [6.6%]), and idiopathic (n=132 [30.1%]) factors. OUTCOMES: We used recurrence, acute kidney injury (AKI; defined as creatinine level increase >= 0.3mg/dL within 48 hours or an increase to 150% of baseline level within 7 days during the sentinel hospitalization), new-onset estimated glomerular filtration rate (eGFR)<60mL/min/1.73m(2) (for >3 months after renal infarction in the absence of a history of decreased eGFR), end-stage renal disease (ESRD; receiving hemodialysis or peritoneal dialysis because of irreversible kidney damage), and mortality as outcome metrics. RESULTS: Treatment included urokinase (n=19), heparin (n=342), warfarin (n=330), and antiplatelet agents (n=157). 5% of patients died during the initial hospitalization. During the median 20.0 (range, 1-223) months of follow-up, 2.8% of patients had recurrent infarction, 20.1% of patients developed AKI, 10.9% of patients developed new-onset eGFR<60mL/min/1.73m(2), and 2.1% of patients progressed to ESRD. LIMITATIONS: This was a retrospective study; it cannot clearly determine the specific causal mechanism for certain patients or provide information about the causes of mortality. 16 patients were excluded from the prognostic analysis. CONCLUSIONS: Cardiogenic origins were the most important causes of renal infarction. Despite aggressive treatment, renal infarction can lead to AKI, new-onset eGFR<60mL/min/1.73m(2), ESRD, and death. PMID- 26545636 TI - Collective Total Syntheses of Atisane-Type Diterpenes and Atisine-Type Diterpenoid Alkaloids: (+/-)-Spiramilactone B, (+/-)-Spiraminol, (+/-) Dihydroajaconine, and (+/-)-Spiramines C and D. AB - The first total syntheses of the architecturally complex atisane-type diterpenes and biogenetically related atisine-type diterpenoid alkaloids (+/-) spiramilactone B, (+/-)-spiraminol, (+/-)-dihydroajaconine, and (+/-)-spiramines C and D are reported. Highlights of the synthesis include a late-stage biomimetic transformation of spiramilactone B, a facile formal lactone migration from the pentacyclic skeleton of spiramilactone E, a highly efficient and diastereoselective 1,7-enyne cycloisomerization to construct the functionalized tetracyclic atisane skeleton, and a tandem retro-Diels-Alder/intramolecular Diels Alder sequence to achieve the tricyclo[6.2.2.0] ring system. PMID- 26545637 TI - Role of the cold biopsy technique in diminutive and small colonic polyp removal: a systematic review and meta-analysis. AB - BACKGROUND AND AIMS: The most commonly detected polyps during screening colonoscopy are diminutive and small polyps, and therefore endoscopic treatment of those polyps is a daily routine for every colonoscopist. The primary aim of this study was to compare the complete eradication rate of diminutive and small colorectal polyps using cold biopsy versus other techniques, because randomized controlled trials have shown conflicting results. METHODS: In March 2015 we searched for randomized controlled trials in Medline, EMBASE, and ISI the Web of Science, starting with their dates of inception, and abstracts of pertinent scientific meetings (eg, American College of Gastroenterology, Digestive Disease Week). The primary outcome was complete removal of diminutive and small polyps (<=7 mm) by histologic eradication rates. The secondary outcome was total procedure time. Using RevMan (Cochrane), we used the Mantel-Haenszel random effects model for binary endpoints and the inverse variance method for continuous outcomes. Grading of Recommendations Assessment, Development and Evaluation was used to rate the quality of evidence for each outcome. RESULTS: Five randomized controlled trials included a total of 668 patients and 721 polyps. Removal techniques included cold biopsy, jumbo biopsy, and cold snare polypectomy. Based on histologic criteria, incomplete polyp removal was significantly lower with cold snare/jumbo forceps biopsy technique than with the cold biopsy technique (relative risk, .40; 95% CI, .26-.62), with no heterogeneity (I(2), 0%). Total procedure time was an average of 2.66 minutes shorter for the cold snare/jumbo forceps biopsy techniques compared with the cold biopsy technique (95% CI, -5.14 to -.18). The quality of evidence was rated moderate. CONCLUSIONS: There is moderate quality evidence that cold snare or jumbo biopsy techniques reduce the risk of incomplete diminutive polyp removal by 60% without increasing the total procedure time. Adequately powered randomized clinical trials are warranted to confirm these findings. PMID- 26545638 TI - Endoscopic treatment of a chronic fistula by resection and sutured closure. PMID- 26545639 TI - [THE DEVELOPMENT OF CLINICAL NUTRITION IN SPAIN (1): INTEGRATING ARTIFICIAL NUTRITION INTO THE SPANISH CLINICAL SETTING]. PMID- 26545640 TI - [THE DEVELOPMENT OF CLINICAL NUTRITION IN SPAIN (2): THE CONTRIBUTION OF SENPE AND "NUTRICION HOSPITALARIA" JOURNAL]. PMID- 26545641 TI - DESCRIPTION OF INDEXES BASED ON THE ADHERENCE TO THE MEDITERRANEAN DIETARY PATTERN: A REVIEW. AB - INTRODUCTION: diet quality indexes are tools are aimed at quantifying the compliance to a defined dietary pattern. These indexes are a combined measure of dietary factors (food groups, foods, nutrients and ratios) and/ or lifestyles factors. The Mediterranean Diet (MD) is a dietary pattern characterized by their positive effects against chronic diseases. There have been many indexes proposed for the assessment of this dietary pattern. An evaluation of their composition and health benefits is therefore convenient. OBJECTIVE: the objective is to evaluate indexes of adherence to the MD with regard to their definition, methodological issues and validation as reported in epidemiological studies. METHODS: we searched in PubMed for studies that developed MD Indexes up to October 2014. RESULTS: a total number of 22 indexes were identified, with differences regarding the number of components (7-28), scoring (0, 1, 2, 3, 4, 5, 8 or 10, in case of compliance), range (0-100) and type of components (which could be food groups/foods or their combination, with nutrients). Among the positive components, fruits and vegetables were the most common and meats, among the negative components. There were also differences with regard to their composition and evaluation (e.g. criteria of moderate alcohol consumption), as well as with the scoring system (in medians, terciles or established servings). CONCLUSIONS: this review suggests that since there is great heterogeneity in the definition of MD. It would be therefore convenient to establish more clearly the components to be included and to establish commonly defined criteria to quantify this dietary pattern. PMID- 26545642 TI - CONSUMPTION OF CHERRIES AS A STRATEGY TO ATTENUATE EXERCISE-INDUCED MUSCLE DAMAGE AND INFLAMMATION IN HUMANS. AB - BACKGROUND: exercise-induced muscle damage (EIMD) is a multifactorial phenomenon that induces muscle function loss because of mechanical and immune stressor stimuli. This immunological stress is mostly caused by inflammation and increased oxidative status. Cherries are fruits that contain a phenolic compound known as anthocyanin, which serves as a pigment in natura. However, research suggests this pigment might provide a potent antioxidant and anti-inflammatory strategy when consumed by humans. OBJECTIVES: the aim of this study was to critically review the literature on cherry consumption focusing on identifying protective strategies against EIMD conferred by it. METHODS: a research was performed in PubMed database. This review presents the results about cherry consumption and EIMD. RESULTS: the articles identified in this review support the notion that tart cherry consumption attenuates EIMD symptoms after intense exercise bouts. This attenuation seems to be related to the antioxidant and anti-inflammatory properties of anthocyanins and other phenolic compounds present in tart cherries. CONCLUSION: daily consumption of tart cherries may attenuate inflammatory and oxidative responses to EIMD, leading to faster recovery after exercise bouts. PMID- 26545643 TI - [METHODOLOGY REVIEW FOR WRITING AND PUBLISHING CASE REPORT: APPLICATIONS ON THE NUTRITION FIELD]. AB - INTRODUCTION: currently, case reports are an important teaching tool with practical applications and contribute to the expansion of knowledge of health professionals. OBJECTIVE: to review the methodology of developing case reports, showing similarities and differences in format and content criteria that are requested for case reports to be published. METHODOLOGY: literature review in PubMed and Scielo between 2005-2015 and manual tracing of the most relevant references of selected articles. INCLUSION CRITERIA: original articles / literature reviews in English / Spanish / Portuguese published in any country and include guidelines or recommendations for the drafting of clinical cases. RESULTS: we found 131 articles, 20 met the inclusion criteria, adding 5 articles by manually tracing. The variables were described: objective, conclusions and recommendations presented in 3 tables; 1. International guide publication; 2. International journals and 3. Latin American journals. DISCUSSION: there are international benchmarks that provide when required to write and publish a case report very specific guidelines. Both international benchmarks analyzed the recommendations are consistent in their usefulness but there is no standardization in its methodology. Very few guidelines mentioned include dietary management, monitoring and evolution in the clinical situation. PMID- 26545644 TI - EFFECT OF CHIA SEED (SALVIA HISPANICA L.) CONSUMPTION ON CARDIOVASCULAR RISK FACTORS IN HUMANS: A SYSTEMATIC REVIEW. AB - INTRODUCTION: chia is a seed rich in such nutrients as proteins, n-3 fatty acids and especially alpha-linolenic acid (ALA), minerals, fibers and antioxidants. Efforts have been made to assess whether human consumption of chia can reduce cardiovascular risk factors; however, it has not been established as effective and the findings of the few studies to have looked into the matter are inconsistent. AIM: to systematize the findings of studies assessing the effect the consumption of chia seed, either milled or whole, has in the prevention/control of cardiovascular risk factors in humans. METHODS: this is a systematic literature review (SLR) with no meta-analysis. The articles scrutinizedwere identified in the electronic databases Lilacs, Medline (Pub- Med version), Cochrane, Scielo, Scopus, and Web of Science under the keywords"dyslipidemia" or "dislipidemia", "hyperlipidemia" or "hiperlipidemia", "obesity" or "obesidade", "salvia"or"salviahispanica", "Lamiaceae" or "chia", "hypertension" or "hipertensao", "hypertrygliceridemia" or "hipertrigliceridemia", and "riscocardiovascular" or "cardiovascularrisk." We chose for our selection English-, Portuguese- or Spanish-language articles about clinical trials on humans and published within the last ten years. The biases of risk analysis were carried out considering 6 of the 8 criteria of the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1. FINDINGS: seven studies (n = 200) fit our inclusion criteria. Of the chosen clinical trials, only one was not randomized. Five of the studies were blind experiments. Two of the studies were acute trials, both of them randomized. Of the chia seed interventions, one study showed a significant drop in systolic blood pressure (SBP) and inflammatory markers, yet there was no change in body mass, lipid profile or blood sugar. In four of the studies reviewed there was a significant spike in ALA and eicosapentaenoic acid (EPA), with no significant change to other parameters. In the acute trials, post-prandial blood sugar was significantly lower. Only one study showed a significant drop in triglycerides (TG), body mass and inflammatory markers; however, the chia seed in that case was mixed with other foods. Most of the studies showed unclear or low risk of bias. Two studies showed a high risk of bias because not all the pre-specified primary outcomes were reported in the findings. CONCLUSION: most of the studies did not demonstrate statistically significant results in relation to cardiovascular disease (CVD) risk factors. The evidence regarding the relationship between chia seed consumption and cardiovascular risk factors are insufficient, and the studies included in this review present numerous limitations. Further research is hence needed. PMID- 26545645 TI - [DO WEIGHT LOSS INCREASE LIFE EXPECTANCY?: SYSTEMATIC REVIEW]. AB - BACKGROUND: prospective trials that assess the effect of weight loss on all-cause mortality have shown controversial results. We conducted a systematic review of prospective studies, with a follow up >=10y, assessing the association of weight loss and weight cycling with all cause- mortality. METHODS: we searched Pubmed of prospective studies with a follow up of >=10y, published from January 1st 2004 to December 31th 2014. RESULTS: nine studies met the inclusion criteria. Five studies assessed the association between weight loss and mortality, two of the studies examined weight cycling and mortality, and two other weight loss and weight cycling with mortality. Weight loss increased all-cause mortality in those that assessed weight loss and mortality. In the two studies evaluating the association between weight cycling and mortality, weight cycling made no difference on mortality. In the two studies assessing weight loss and weight cycling, results showed weight cycling increased mortality in both of them, and weight loss increased mortality in one study. CONCLUSION: six out of seven (>=10 y of follow up) prospective studies showed that weight loss was associated with increased mortality; the results from studies assessing weight cycling were inconsistent. None of the studies found evidence showing that weight loss improved life expectancy. PMID- 26545646 TI - [EFFECTS OF INGESTING CARBOHYDRATE-PROTEIN SUPPLEMENTS DURING EXERCISE ON ENDURANCE PERFORMANCE: A SYSTEMATIC REVIEW]. AB - INTRODUCTION: sports drinks aid to improve physical performance significantly because of its content of carbohydrate, electrolytes and water. However, in recent decades it has been found that drinking a sports drink with protein during exercise improves endurance performance, produces lower losses of body weight induced by dehydration and helps to reduce post-exercise muscle damage compared to a drink only with carbohydrate and electrolytes. PURPOSE: the aim of this study was to analyze the main studies about the effectiveness of a supplement intake with carbohydrate, protein and electrolytes during exercise. METHODS: studies were identified by searching Google Scholar, EBSCO, PubMed and Scopus using the following search terms: Carbohydrate-protein and performance and Added protein and sports drink. The methodological quality of the trials was evaluated, and It was considered that the intake of the supplement has been during exercise. RESULTS: twenty articles were included in this study. Thirteen obtained results were the intake of sports drinks with protein produced significant improvements on endurance performance compared to beverages with carbohydrates and electrolytes alone, or a placebo. DISCUSSION: increase the caloric content of sports drinks to add protein was probably a better strategy than reduce the carbohydrate content to match the amount of calories. CONCLUSIONS: protein intake during exercise demonstrated an ergogenic effect on endurance performance when assessed by time to exhaustion. However, we need more evidence to prove this possible ergogenic effect of protein. PMID- 26545647 TI - [ENERGY AND MACRONUTRIENT INTAKE IN FEMALE ATHLETES]. AB - Objetive: to determine the adequate intake of macronutrients to improve the nutritional status of women athletes and their sports performance. METHODS: a search was performed in four databases: EBSCO, Proquest, Pubmed and OvidSP, using the keywords "protein intake" AND "athletes", "endurance athletes" AND "nutrition". SELECTION CRITERIA: original articles about protein intake in female athletes, published between 2009 and 2014, and whose source are indexed scientific journals. RESULTS: 722 articles were identified, of which only 1.4% were considered to be included. 100% were completed clinical trials and published abroad, 50% in the US. 20% were exclusive studies of female athletes and 80% included men and women in the sample. In 70% of studies female athletes presented energy deficiencies; in protein intake, 70% met the dietary recommendations; carbohydrate intake was inadequate in 90% of clinical trials and in 50% of cases women had a high intake of fat. CONCLUSION: there is lack about nutrition in female athletes in Europe and internationally. Female athletes consume less energy and macronutrients that male athletes. There is no consensus on the recommended protein range and there are differences in consumption depending on the type of exercise being performed. It is recommended to carry out an agreement between scientific institutions about energy intake and macronutrient in sport, with particular emphasis on women. PMID- 26545648 TI - [EFFECTS OF WHOLE-BODY VIBRATION TRAINING ON BODY COMPOSITION AND PHYSICAL FITNESS IN RECREATIONALLY ACTIVE YOUNG ADULTS]. AB - In the last decade, it has been suggested that whole- body vibration training (WBV) may increase neuromuscular performance and consequently affect the muscular improvement as either acute response to vibration or chronic adaptation training. Vibrating platforms generate frequencies from 5-45 Hz and vertical oscillations of 1-11 mm peak to peak, affecting more or less intensity acceleration changing by combining frequency and amplitude. Vibration training, in a session as various offers different results in regard to changes in body composition and in increasing the vertical jump, sprint, and the different manifestations of force development. These promising results await further research to establish parameters (duration, frequency and amplitude) with vibration stimulation in young active subjects. This literature review provides an update on the scientific evidence on the body vibrations in order to answer the question whether WBV, meaning the exercise by increasing the gravitational load collection, is a treatment option if the aim is to improve neuromuscular function, flexibility, balance, agility, coordination and body composition. PMID- 26545649 TI - [EFFECT OF LOW CARBOHYDRATE DIETS ON WEIGHT LOSS AND GLYCOSILATED HEMOGLOBIN IN PEOPLE WITH TYPE 2 DIABETES: SYSTEMATIC REVIEW]. AB - INTRODUCTION: some experts have suggested out that low carbohydrate diets (LCD) are more effective for weight loss and glycemic control. However, long term results are controversial. OBJETIVE: to review and analyze randomized control studies that evaluate the effect of LCD on weight and metabolic control in individuals with type 2 diabetes for a period equal to or greater than 10 months. METHODS: a systematic review was conducted on randomized trials registered in PubMed, EBSCOhost and Scielo to May 15th 2015, published in English and Spanish, with the following search data: "diabetes mellitus" AND "carbohydrate restricted diet" OR "restricted carbohydrate diet" OR "low carbohydrate diet" AND "weight loss". RESULTS: four studies met the inclusion criteria. There were 444 participants between 18-70yo. Follow-up time ranged between 10 to 24 months. Three out of the four studies reported weight reduction with LCD. However, when LCD were compared with other diets no significant differences in weight loss or A1C levels were observed. CONCLUSIONS: this review showed that three of four studies on the LCD were effective for weight loss over a period of 10 to 24 months. However, there was no evidence showing better results than those observed with other diets. Nor, difference in A1C. PMID- 26545650 TI - [THE EFFECTS OF THE PILATES METHOD ON HAMSTRING EXTENSIBILITY, PELVIC TILT AND TRUNK FLEXION]. AB - INTRODUCTION: Pilates includes a high volume of hamstring stretching and maximal trunk flexion with knees extended exercises. OBJECTIVE: to perform a systematic review about Pilates practice effects and a detraining period on hamstring extensibility, pelvic tilt and trunk flexion in maximal trunk flexion with knees extended. METHOD: it was analysed all the experimental or quasi-experimental designs written in English, Spanish or Portuguese and included in the following databases: Pubmed, Sports Discus, ISI Web of Knowledge, Dialnet and Research Gate. RESULTS AND DISCUSSION: twenty-one papers were analysed. Most of them used a pre-test-post-test design with control group. The intervention programs applied were heterogeneous. Samples were composed mainly of women, both young and old. It was found that the Pilates practice, with different volume, significantly increased hamstring muscle extensibility and pelvic tilt in maximal trunk flexion. At least three training sessions peer week during six weeks were necessary in order to obtain a high trunk inclination. Studies which involved athletes showed contradictory results. By inducing a detraining period it was noticed a decrease in hamstring extensibility and trunk flexion from the second week. CONCLUSIONS: there is a moderate evidence that Pilates is an effective method to increase hamstring extensibility, pelvic tilt and the degree of trunk flexion in maximal flexion positions in sedentary and recreational active people and also to increase hamstring extensibility in athletes. PMID- 26545651 TI - EVOLUTION OF THE INTAKE AND NUTRITIONAL RECOMMENDATIONS OF CALCIUM AND VITAMIN D FOR THE LAST 14 YEARS IN SPAIN. AB - INTRODUCTION: calcium and vitamin D are essential for the human being. Scientific evidence supports the correlation between both nutrients and their essential processes in the correct functioning of the human's organism, which is what justifies the increase of the recommended ingestion in Spain, since 2001 until nowadays. OBJECTIVES: to analyse the evolution on calcium and vitamin D ingestion related to the evolution of the Dietary Reference Intake, as well as its repercussion, since 2001 until nowadays. DESIGN/SETTING: a bibliographical search in major scientific data bases, PubMed, SciELO and EMBASE was conducted. SUBJECTS: a review focused on the scientific literature on vitamin D and calcium, the evolution of its intake, changes in nutritional recommendations and the importance and consequences of these aspects. RESULTS: actual ingestion of calcium and vitamin D, during this period of time, has decreased in Spain, reaching average consumption values below recommended. CONCLUSION: it may be necessary to increase the consumption of supplements and fortified foods, in some specific cases, in order to achieve the Dietary Reference Intake. PMID- 26545652 TI - [EARLY MOTHER-CHILD BONDING FACTORS ASSOCIATED WITH CHILDREN OBESITY]. AB - The aim of this study is to describe the experience of a group of mothers with obese children, regarding how early bond affects the relationship that both have with food and this, in turn, impacts on childhood obesity. The present study has a qualitative, exploratory and descriptive design. The sample consists of five chilean women between 22 and 39 years old, with obese children between 2 and 4 years old. In-depth interviews were carried out and open coding strategy was used as method of analysis. Results show a tendency of mothers to establish insecure attachment relations, difficulties of tuning and expression of affection, and a predominance of a permissive parenting style around food. This has important implications for prevention and treatment of obesity, focusing on the attachment bond between mother and child. PMID- 26545653 TI - [LEVELS OF OBESITY, METABOLIC PROFILE, CONSUMPTION OF TABACO AND BLOOD PRESSURE IN SEDENTARY YOUTHS]. AB - BACKGROUND: in Chile, the National Health Survey (ENS) conducted in 2009-2010 reported high prevalence of overweight, sedentary lifestyle, high cholesterol and metabolic syndrome in the population. OBJECTIVE: to determine the prevalence in young sedentary obesity and consumption of tabaco and analyze their association with the metabolic profile, body fat percentage and blood pressure. PATIENTS AND METHODS: 125 young sedentary, 26 men and 99 women, aged between 17 and 29 years old were evaluated. Body mass index (BMI), percent body fat (% fat), waist contour (CC), systolic and diastolic blood pressure, total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides: measurements were performed, glycemia and consumption of snuff. RESULTS: HDL-C (p = 0.000) and% MG (p = 0.043) were higher in women. 37.6% of young people turned smoker. 35, 2% of the sample showed excessive malnutrition. Obese subjects had higher levels: waist contour (p = 0.000) and% FM (p = 0.000). When analyzing obesity DC, this showed significant differences in BMI,% fat, systolic and diastolic blood pressure. BMI presented positive association with CC,% fat, total cholesterol, triglycerides, LDL, systolic and diastolic blood pressure (p < 0.05). The CC presented association with MG%, triglycerides, systolic blood pressure and diastolic (p < 0.05). The MG% did not present association with other variables CONCLUSIONS: a high prevalence of malnutrition by excess consumption of tabaco in the study sample, while other variables are not high-risk categories, it is an opportune time to intervene and reverse these negative health trends now. PMID- 26545654 TI - [TWELVE WEEKS OF PHYSICAL EXERCISE INTERVAL WITH SURCHARGE IMPROVES THE ANTHROPOMETRIC VARIABLES OF OBESE MORBID AND OBESE WITH COMORBIDITIES CANDIDATES TO BARIATRIC SURGERY]. AB - INTRODUCTION: for the morbid obesity the bariatric surgery is effective, but to major preoperative weight it might increase morbidity and mortality, for such a motive it is necessary to implement programs that improve this condition. OBJECTIVE: to determine the effects of a program of physical exercise interval on the anthropometric profile of the morbidly obese and obese with comorbidities candidates to bariatric surgery. MATERIAL AND METHODS: three men and twenty-five women between 18 and 60 years old candidates to bariatric surgery, with morbid obesity (n = 16) or obese and comorbidities (type-II diabetes mellitus, hypertension, dyslipidemia, insulin resistance) (n = 12), they were subjected to a program of physical exercise with interval overload of three months duration (36 sessions). Before and 72 hours after the last intervention session was evaluated on fasting (>= 12 hours): body weight, body mass index (BMI), waist contour (WC) and contour hip. RESULTS: the average age corresponds to 36.96 years, prior to intervention the weight had an average of 102.66 +/- 15.96 kg, BMI of 40.84 +/- 4.94, the WC 114.22 +/- 10.35 cm and the contour hip 126.84 +/- 10.65 cm. After twelve weeks of intervention showed significant decreases in weight variables (p = 0.000), BMI (p = 0.001), WC (p = 0.000) and hip contour (0.000). CONCLUSIONS: twelve weeks of interval exercise improved preoperative anthropometric conditions, without presenting risks in health and with high adherence to the program, which is why it may be recommended for this type of treatment. PMID- 26545655 TI - EFFECT OF HYPOENERGETIC DIET COMBINED WITH CONSUMPTION OF COCONUT FLOUR IN OVERWEIGHT WOMEN. AB - INTRODUCTION: the prevalence of obesity has increased, especially among women. AIM: the aim of this study was to assess the effect of a hypoenergetic diet combined with coconut flour on anthropometric and biochemical data and the quality of the diet. METHODS: we carried out a crossover clinical trial involving a step with hypoenergetic diet only and another with the diet associated with coconut flour consumption (26 g) over the course of nine months. The volunteers were recruited from the Sao Goncalo city of Rio de Janeiro. Anthropometric, biochemical and dietary data were collected monthly. The diet quality index revised for the Brazilian population (DQI-R) and the consumption of ultra processed foods and additives were assessed. The Wilcoxon and Mann-Whitney tests were performed, with p < 0.05 considered statistically significant. RESULTS: forty-two women of an average 47.5 +/- 9.5 years of age participated. The hypoenergetic diet promoted a decrease in body fat, body mass index, waist circumference, waist-to-height ratio, visceral adiposity index, diastolic blood pressure, triglycerides and VLDL. The consumption of coconut flour promoted a drop in glucose and total cholesterol levels when supplementing the hypoenergetic diet. The improvement to diet quality can be noted in the decrease in consumption of ultra-processed foods like vegetable oil, chocolate and soft drinks. CONCLUSION: the hypoenergetic diet promoted a decrease in the anthropometric parameters, blood pressure and triglycerides. The consumption of coconut flour promoted a decrease in glucose and total cholesterol levels when supplementing the hypoenergetic diet. The improved diet quality can be seen in the decrease in consumption of ultra- processed foods. PMID- 26545656 TI - [THE MANAGEMENT OF QUALITATIVE AND QUANTITATIVE DIETARY TREATMENT FOR OVERWEIGHT AND OBESITY: METHODOLOGY AND A NEW PERSPECTIVE ON INDIVIDUALISED ASSESSMENT]. AB - %WL: percentage of weight loss; % FL: percentage of fat loss. OBJECTIVE: to describe the management methodology of a qualitative and quantitative dietary treatment for overweight and obesity. METHOD: 4,625 consultations were conducted with 616 overweight and obese patients over the age of 25 in the south-east of Spain between 2006-12. A balanced, low-calorie, qualitative and quantitative diet based on locally grown food was employed. The weight loss and maintenance dietary treatment methodology is described, as are the units of measurement considered suitable for the expression of successful weight loss; a new vision of individualised counselling and multidisciplinary treatment. RESULTS: 80% of patients obtained a % FL >= 5% (22.6+/-11.8-11.2+/-7.4), and attended appointments for more than a month and a half. CONCLUSION: the dietary treatment methodology is described; units of measurement are recommended for use in consultations and in clinical trial publications, creating a precedent with a degree of evidence on how to determine successful weight loss; it is recommended to measure hip and waist perimeters and incorporate a study of body image; a new vision of individualised assessment and advanced multidisciplinary care is presented, independent of age, pregnancy and physical disabilities. The health care professional's position should be seen as that of the person responsible for determining which techniques might be most effective in such loss. PMID- 26545657 TI - NUTRITIONAL AND METABOLIC ASSESSMENT IN OVERWEIGHT PATIENTS WITH AND WITHOUT HYPERPROLACTINEMIA CAUSED BY PROLACTINOMA. AB - INTRODUCTION: prolactinomas are pituitary adenomas that express and secrete prolactin. These patients are overweight and the mechanisms are being studied. GOALS: assess nutritional and metabolic status of overweight patients with and without hyperprolactinemia caused by prolactinoma and compare them. MATERIALS AND METHODS: cross-sectional study, patients with body mass index (BMI) >= 25 kg/m2 with and without prolactinoma: 1) 20 normoprolactinemic (NPrl) with prolactinoma; 2) 23 hyperprolactinemic (HPrl) with prolactinoma; 3) 28 controls without prolactinoma or alterations in prolactin levels. Evaluated through anthropometric, dietetics, and biochemical assessment. RESULTS: of the 71 patients evaluated, most were obese women with macroprolactinomas. All three groups had diets with low caloric and monounsaturated fatty acid (MUFA) intake, the NPrl group had low carbohydrate (CHO) intake and high lipid (LIP) and saturated fatty acid (SFA) intake, and the NPrl and HPrl groups had appropriate intake of polyunsaturated fatty acids (PUFA). The HPrl group had elevated total cholesterol. HDL cholesterol was below the recommended threshold for most patients. No statistically significant differences were found in anthropometric and biochemical variables among the groups. CONCLUSIONS: most patients with prolactinomas and controls are obese and metabolically similar regardless of prolactin levels. All groups presented low caloric and MUFA intake. Protein, LIP, SFA, and cholesterol were significantly different among the groups, the NPrl group ingested less amount of protein and greater of fat. Snacking between meals and changes of food consumption on weekends was reported by most patients. This is the first study comparing patients with prolactinomas and controls, both with overweight, regarding food consumption and feeding behavior. PMID- 26545658 TI - NUTRITIONAL STATUS, DIET AND NON-ALCOHOLIC FATTY LIVER DISEASE IN ELDERS. AB - OBJECTIVE: evaluate the inter-relations between non-alcoholic fatty liver disease (NAFLD) and dietary factors in a population of hypertensive elders. METHODS: 229 hypertensive elder patients were evaluated, from June to December 2009. All the patients that accepted to participate in the study signed a free consent term. An anthropometric evaluation was carried out and the body composition was evaluated. The diagnosis of NAFLD was determined by the American guidelines. The regular food intake was estimated through a 24 hour questionnaire. RESULTS: the weighted excess, by the body mass index and excess of abdominal fat, were associated with NAFLD (p < 0.001). An inverse profile was found with the diet variables. CONCLUSION: the studied group presents a health risk situation, considering the nutritional status markers. The regular diet appeared to be inadequate, showing excess of sodium and low fiber and vegetables intake. PMID- 26545659 TI - [ACCURACY PARAMETERS AS INDICATORS OF ANTHROPOMETRIC ADIPOSITY VISCERAL SCHEDULED FOR TWO-DIMENSIONAL EQUATION]. AB - INTRODUCTION: anthropometric indicators are easy to apply and can help identify the accumulation of visceral fat, which favors the occurrence of cardiovascular events, increasing morbidity and mortality from chronic degenerative diseases. OBJECTIVE: to evaluate the accuracy of anthropometric indicators for the location of abdominal fat in determining visceral adiposity. SUBJECTS/METHODS: cross sectional study conducted among patients attending outpatient, of both sexes, aged over 20 years. Evaluated: Waist Circumference (WC), Waist-Hip Ratio (WHR), waist-to- stature ratio (CER), conicity index (CI); Sagittal Abdominal Diameter (DAS); Coronal Diameter (DC); Mass Index (BMI), percentage of body fat (% BF); Visceral Adiposity (AV/AS) predicted by the formula , fasting glucose , total cholesterol (TC), Low Density Lipoprotein (LDL), high density lipoprotein (HDL), Very Low Density lipoprotein (VLDL) and Triglycerides (TG). RESULTS: 129 patients were included, mean age 51, 06 + 14.02 years and a higher prevalence of adults (72,9%) and female (75,2%). CC 102,9 (+ 10,82 ), CI 2,08 (+ 0,13), and the AV/AS 1,03 (+ 0,16), showed high values with statistical significance among men, p. PMID- 26545660 TI - [VALUES OF WAIST/HIP RATIO AMONG CHILDREN AND ADOLESCENTS FROM BOGOTA, COLOMBIA: THE FUPRECOL STUDY]. AB - OBJECTIVE: the aim was to establish reference standards for waist/hip ratio among Colombia children and adolescent aged 9 to 17.9 years who participated in "The FUPRECOL Study". METHODS: cross-sectional study. A sample of 3 005 children and 2 916 adolescents healthy Colombian youth (boys n = 2 542 and girls n = 3 384) participated in the study. Height, weight, waist circumference, hip circumference and sexual maturation status were measured. Reference curves were fitted with the LMS method (L [curve Box- Cox], M [curve median] and S [curve coefficient of variation]), for boys and girls, stratified by age group, and to compare them to international references. RESULTS: in all ages, the waist/hip ratio was higher in boys than in girls. Subjects whose waist/hip ratio was above the 90th percentile of the standard normal distribution were considered to have high cardiovascular risk (boys range 0.87 to 0.93 and girls range 0.85 to 0.89). Overall, our waist/hip ratio values were lower than Europe, Asia and Africa values and similar to those of some Latin American references. CONCLUSIONS: values reference charts for waist/hip ratio values specific for age and sex, obtained from children and adolescents from Bogota, Colombia, are provided. They may be used regionally, both for nutritional assessment and to predict cardiovascular risks in early age. PMID- 26545661 TI - [BREASTFEEDING PROBLEMS AND OTHER FACTORS ASSOCIATED WITH EXCESSIVE NEONATAL WEIGHT LOSS IN A SOCIAL SECURITY HOSPITAL IN LIMA, PERU]. AB - INTRODUCTION: during the first days of life the mother is the main source of nutrients for the newborn. However, breastfeeding difficulties are common and may generate excessive neonatal weight loss. OBJECTIVE: estimate the magnitude and association between breastfeeding problems and excessive neonatal weight loss beyond the physiological norm in the neonatology ward in a social security hospital in Lima, Peru. METHODS: we conducted a cross sectional analysis of the recorded neonatal weight in a routine evaluation (between 24 and 72 hours of life) and compared it against birth weight. Excessive weight loss was defined as a difference greater than or equal to 7 %. Breastfeeding problems (defined as problems with breastfeeding initiation, mouth position, breastfeeding duration, breastfeeding frequency, too much clothing, nipple pain and C form) were investigated using a survey and visual verification. The association between excessive weight loss and breastfeeding problems, adjusted by other factors, was quantified using a multiple generalized linear model. RESULTS: excessive weight loss was present in 18.8% (74/393) of the newborns. Improper positioning of the mouth on the nipple was present in 53.7% (211/393) of neonates while nipple pain was reported by 44.0% (173/393) of mothers. In the adjusted analysis, nipple pain [PR = 1.50 (95% CI: 1.02 to 2.22)] and improper positioning of the mouth [PR = 1.67 (95% CI: 1.09- 2.57)] were associated with an increased occurrence of excessive neonatal weight loss. CONCLUSIONS: breastfeeding problems are common. These difficulties are significantly associated with an increased occurrence of excessive neonatal weight loss. Improvements in breastfeeding practices, for example through educational programs, may decrease the occurrence of excessive neonatal weight loss. PMID- 26545662 TI - ANEMIA IN PREGNANCY: IMPACT ON WEIGHT AND IN THE DEVELOPMENT OF ANEMIA IN NEWBORN. AB - INTRODUCTION: nutritional deficiencies are still a common problem during pregnancy causing anemia. Gestational anemia is still considered a public health problem in Brazil, because it is hazardous to both mother and fetus, and is associated with increased risk of maternal-fetal morbidity, as well as the nutritional status of child. OBJECTIVE: to evaluate the frequency of maternal gestational anemia in newborns and its relation to the nutritional status of the child at birth. METHODS: anthropometric data of pregnant women and their newborns were obtained. Blood was collected from pregnant women and the umbilical cord of newborns for analysis of hemoglobin, hematocrit, RDW, iron, ferritin and transferrin saturation index in automatic devices. The results are presented such as the arithmetic mean and the standard deviation. GraphPadinStat Software version 3.0 was used, with a maximum significance level of 5%. RESULTS: the frequency of maternal anemia was 53.7%, and 32.6% in newborns. Half the newborns were anemic children of anemic mothers. 79.3% of the anemic pregnant women had mild anemia and in 20.7% moderate. The average concentration of hemoglobin and hematocrit was lower in anemic pregnant women (9.7 +/- 0.9 g/dL and 29.8 +/- 3.2%) compared with non-anemic (11.9 +/- 0.7 g/ dL and 36.5 +/- 2.7%). The maternal iron was positively correlated with ferritin (r = 0.3889, p = 0.01) from umbilical cord blood. The newborns' weight, length and head circumference of anemic mothers were 3 375.9 +/- 506,9 g, 51.2 +/- 1.7 cm and 34.5 +/- 1.5 cm, respectively, while of nonanemic mothers were 3 300.2 +/- 458,4 g, 50.3 +/- 2.0 cm and 34.2 +/- 2.0 cm, respectively. There were no significant correlations between maternal hemoglobin, iron and ferritin with weight, length and head circumference of newborns. CONCLUSION: the results of this study show that maternal iron deficiency anemia (mild to moderate) can affect the blood profile and iron concentrations in umbilical cord blood of newborns, but without interfering with the child's anthropometric parameters. PMID- 26545663 TI - DEVELOPMENT AND VALIDATION OF TWO FOOD FREQUENCY QUESTIONNAIRES TO ASSESS GLUTEN INTAKE IN CHILDREN UP TO 36 MONTHS OF AGE. AB - BACKGROUND AND OBJECTIVE: precise information on gluten consumption is crucial for specifically studying the impact of gluten introduction and gluten intake in celiac disease development. Our aim was to develop and validate tools (food frequency questionnaires, FFQs) for the assessment of gluten consumption in Spanish children aged 7-36 months. METHODS: a total of 342 children, who attended primary healthcare centers for routine health surveys or La Fe Hospital for minor health problems as well as healthy children (recruited in nurseries and primary schools) participated in this survey. We have developed two different FFQs (one for 7-12 months and other for 13-36 months). For validation, results from two FFQs were compared with results of 2-day food records and also with the gold standard 7-day records. The mean gluten intake obtained by the 2DR vs. FFQ and the 7DR vs. FFQ, were compared using the Bland Altman plot method and also Lin's concordance correlation coefficient. RESULTS: we found a good agreement between our FFQs and the 2DR and 7DR according to the results of both the Bland-Altman plots and Lin's concordance correlation coefficient. CONCLUSIONS: our two new FFQs are therefore the only validated questionnaires available to determine gluten consumption in Spanish children. They are user-friendly and offer excellent instruments to assess gluten intake in children up to 36 months of age. PMID- 26545664 TI - [EATING DISORDERS IN PEDIATRIC AGE: A BOOM PATHOLOGY]. AB - AIMS: to determine the characteristics of pediatric patients suffering from eating disorders that were hospitalized at Hospital Universitario de Canarias. MATERIALS AND METHODS: a retrospective study in a cohort of pediatric patients diagnosed with eating disorders and admitted in our area was developed during the last seven years. RESULTS: out of 35 patients in our study, 85.7 % were women, onset average age 13.5. 77.1% of the cases were diagnosed as anorexia nervosa- restrictive type. The most frequent analytical alterations, detected when patients were in hospital, consisted in a drop in plasma levels in retinol binding protein (RBP)- in 57.6% of the cases- and D hypovitaminosis- in 46.9 % of them: the use of high - calories supplements was required in 71.4% of patients during hospitalization. The average weight gain was higher when the body mass index (BMI) was smaller at patient's admission to hospital (p = 0,006). Conclussions: eating disorders are increasing in pediatric age: puberty is a special vulnerable period for its development, as well as medical complications secondary to malnutrition. Admission to hospital is an essential tool for handling many cases; taking the necessary monitoring leading to a weight increase, preventing complications in nutritional support and tackling the underlying psychopathology. Diagnosis and a precocious treatment are crucial to avoid an excessive weight loss and more complications. PMID- 26545665 TI - [UNHEALTHY FOOD INTAKE IS LINKED TO HIGHER PREVALENCE OF METABOLIC SYNDROME IN CHILEAN ADULT POPULATION: CROSS SECTIONAL STUDY IN 2009-2010 NATIONAL HEALTH SURVEY]. AB - INTRODUCTION: metabolic syndrome (MS) is a clustering of risk factors known to promote cardiovascular disease and diabetes. Environmental factors, such as unhealthy diet, play a major role in the development of this condition. In this study, we evaluated the prevalence of MS and its association with food intake quality among Chilean adults. METHODS: we analyzed data of 2 561 adults (>= 18 years-old) included in the last National Health Survey (NHS 2009-2010) who had appropriate information to diagnose MS based on ATP III-NCEP guidelines. Consumption frequency of fish, whole grains, dairy, fruits and vegetables was also analyzed and associated with MS prevalence. Using a healthy diet score (HDS), we described the overall diet quality and further correlated it with MS prevalence. RESULTS: we found that lower whole grain intake was associated with greater MS prevalence (OR = 1.78; 95% CI: 1.088-2.919; p = 0.022). HDS showed better diet quality among women and in subjects with increasing age and higher educational level. A HDS < 3 points was associated with an increased risk of MS (OR HDS < 3 / HDS >= 3 = 3.69; 95% CI 1.884-7.225, p < 0.001). CONCLUSION: Chilean adult population exhibits a high prevalence of MS linked to a poor diet quality. PMID- 26545666 TI - DIAGNOSIS OF METABOLIC SYNDROME IN CHILDREN AS A POTENTIAL INDICATOR OF TECHNICAL ABILITY IN MEDICAL AND NUTRITIONAL CARE. AB - BACKGROUND: currently, there is an increase in the incidence of obesity in the pediatric population, which is associated with an increase in metabolic syndrome (MetS). Thus, an early diagnosis of MetS is needed in this population to improve the prevention of cardiovascular disease and type 2 diabetes in adulthood. OBJECTIVE: the aim of this study was to explore the ability of health professionals to identify the main criteria for MetS in children, which is required for establishing the conditions for early diagnosis and timely treatment. METHODS: a cross-sectional study was conducted using a survey and conducted in two states of the republic (Aguascalientes and Hidalgo) and in the Federal District from January to December 2014. RESULTS: the questionnaire was applied to 274 health professionals. Most of these professionals (61.7%) reported knowledge of the criteria for MetS diagnosis in children and adolescents. Additionally, it was observed that 63.1% of professionals did not perform the needed measurements the waist of circumference in preschool children and that 46.4% did not measure them in school children. However, 64.6% of professionals performed the measurements in adolescents. CONCLUSIONS: this study found that health professionals providing care to pediatric patients do not know the parameters and cutoff points for MetS diagnosis. They do not conduct a deliberate search for MetS risk factors, which is a major limitation for diagnosis and early treatment. Therefore, we suggest a systematic approach for maintaining the standards of health professionals and to make determining the criteria for proper diagnosis of MetS a target of clinical practice. PMID- 26545667 TI - EFFECTS OF OATS ON LIPID PROFILE, INSULIN RESISTANCE AND WEIGHT LOSS. AB - INTRODUCTION: cardiovascular diseases are the main cause of morbidity worldwide. Such prevalence justifies the importance of functional foods that promote cardiovascular health, like ?-glucan present in oats, with potential hypocholesterolemic and hypoglycemic effects. OBJECTIVE: to evaluate the effects of an intervention with oats in blood glucose levels, HOMA-IR index, lipid profile, weight and Body Mass Index (BMI) of adult users of a health service in the interior of Rio Grande do Sul, Brazil. METHODS: longitudinal study, case control type with before and after experiment, conducted with individuals that are 22-60 years old, users of a health service. The individuals were distributed in Control (usual diet) and Case (usual diet + 40 g oats/day) groups. There was performed, at the beginning of the study and after eight weeks of monitoring, measuring of height and weight, calculation of BMI (kg/m2), blood collection for measurement of fasting glucose, insulin, total cholesterol, triglycerides and HDL cholesterol; and there were calculated the LDL cholesterol and HOMA-IR index. The data was expressed as mean +/- standard deviation and percentages. The Kolmogorov Smirnov test, Student t test, Mann-Whitney and Wilcoxon tests were applied. A significance level of 5% was adopted (p < 0.05). RESULTS: the sample consisted of 82 subjects, divided into cases (n = 38) and controls (n = 44), mean age 40.07 +/ 10.49 years old, 58.5% were women. Comparing the results of all measured parameters at baseline and after eight weeks of monitoring, the Control group did not achieve a significant reduction in any parameter, showing a significant increase in blood glucose and HOMA- IR (p < 0.05). The Intervention group had a significant reduction of all anthropometric and biochemical parameters analyzed (p < 0.001). CONCLUSION: the findings demonstrate the beneficial effects of oats to cardiovascular health through significantly improving of the lipid and glycemic profiles, being a potential adjuvant in the prevention and treatment of metabolic disorders. PMID- 26545668 TI - [STUDIES IN VITRO INHIBITION OF THE ANGIOTENSIN-CONVERTING ENZYME-I, HYPOTENSIVE AND ANTIHYPERTENSIVE EFFECTS OF PEPTIDE FRACTIONS OF V. UNGUICULATA]. AB - Inhibition of angiotensin-converting enzyme I (ACE-I) in vitro and in vivo from peptide fractions by enzymatic hydrolysis of the Vigna unguiculata protein concentrate was evaluated. Hydrolysis was done with Pepsin-Pancreatin and Flavourzima in two separate systems. The resulting hidrolysates were ultrafiltrated to obtain fractions with different molecular weight. The fractions with better inhibition Flavourzima were size > 1 kDa (> 1 kDa-F) and < 1 kDa (< 1 kDa-F), with an IC50 of 1222.84 and 1098.6 MUg/ml respectively. Pepsin-Pancreatin fraction. PMID- 26545669 TI - GANODERMA LUCIDUM IMPROVES PHYSICAL FITNESS IN WOMEN WITH FIBROMYALGIA. AB - INTRODUCTION: fibromyalgia is a chronic disease characterized by generalized pain, stiffness, poor physical conditioning, non-restorative sleep and poor health-related quality of life. Ganoderma lucidum a type of mushroom that has demonstrated several benefits in different populations. Ceratonia siliqua is a natural therapy rich in antioxidants with potential benefits on health. OBJECTIVE: to evaluate the effects of 6-week treatment of Ganoderma lucidum and Ceratonia siliqua on physical fitness in patients suffering from fibromyalgia. METHODS: sixty-four women with fibromyalgia participated in the study. They took 6 g of Ganoderma lucidum or Ceratonia siliqua per day for 6 weeks. Different fitness tests were selected in order to evaluate functional capacity. RESULTS: after the 6-week treatment period, Ganoderma lucidum significantly improved aerobic endurance, lower body flexibility, and velocity (p < .05). No significant improvement in any physical test was observed in the Ceratonia siliqua group. DISCUSSION AND CONCLUSION: Ganoderma lucidum may improve physical fitness in women with fibromyalgia, whereas, Ceratonia siliqua seemed to be ineffective at increasing physical fitness. These results may indicate that Ganoderma lucidum might be a useful dietary supplement to enhance physical performance of the patients suffering from fibromyalgia. PMID- 26545670 TI - NOVEL INSIGHTS ON INTAKE OF MEAT AND PREVENTION OF SARCOPENIA: ALL REASONS FOR AN ADEQUATE CONSUMPTION. AB - INTRODUCION: sarcopenia is defined as a syndrome characterized by progressive and generalized loss of muscle mass and strength. The main cause of sarcopenia is the alteration of protein metabolism, in which the proteolytic processes are not accompanied by an appropriate protein synthesis and muscle cells lose progressively the sensitivity to the anabolic stimulus. The most rational approach to delay the progression of sarcopenia and counteract the anabolic resistance is proper nutrition. Meat contains biologically active compounds, such as creatine, carnitine, Conjugated Linoleic Acid (CLA) which have significant impacts upon human protein metabolism. METHODS: we performed a narrative literature review to evaluate the till-now evidence regarding: 1. adequate intake of meat in elderly as a topic for prevention of sarcopenia; 2. the correct intake of biologically active compounds contain in meat, which have significant impacts upon human protein metabolism and so have beneficial effects on prevention of sarcopenia. This review included 62 eligible studies. RESULTS: the results demonstrated that in elderly the optimum diet therapy for the sarcopenia prevention and treatment, which must aim at achieving specific metabolic goals, must recommend the consumption of 113 g of meat (220 kcal; 30 g protein) five time a week. CONCLUSION: in a varied and balanced diet, for preventing sarcopenia, it is recommended to assume meat 4-5 times a week (white meat 2 times per week, lean red meat less than 2 times per week, processed meat less than 1 time per week), as suggested in the diet pyramid for elderly. PMID- 26545671 TI - A COCONUT EXTRA VIRGIN OIL-RICH DIET INCREASES HDL CHOLESTEROL AND DECREASES WAIST CIRCUMFERENCE AND BODY MASS IN CORONARY ARTERY DISEASE PATIENTS. AB - INTRODUCTION: saturated fat restriction has been recommended for coronary arterial disease, but the role of coconut oil (Cocos nucifera L.) extra virgin, lauric acid source in the management of lipid profile remains unclear. OBJECTIVE: to evaluate the effect of nutritional treatment associated with the consumption of extra virgin coconut oil in anthropometric parameters and lipid profile. METHODS: we conducted a longitudinal study of 116 adults of both sexes presenting CAD. Patients were followed in two stages: the first stage (basal-3 months), intensive nutritional treatment. In the second stage (3-6 months), the subjects were divided into two groups: diet group associated with extra virgin coconut oil consumption (GDOC) and diet group (DG). Held monthly anthropometric measurements: body mass, waist circumference (WC), neck circumference (PP), body mass index (BMI). Gauged to collected blood pressure and blood samples were fasted for 12 hours, for total cholesterol analysis and fractions apoproteins (Apo A-1 and B), glucose, glycated hemoglobin (HbA1C), insulin (I). Comparing the averages at the beginning and end of the study employing the paired Student t-independent. And set the diastolic blood pressure by BMI using ANOVA. Analyses were performed using the SPSS statistical package, being significant p < 0.05. RESULTS: the mean age of the population was 62.4 +/- 7.7 years, 63.2% male, 70% elderly, 77.6% infarcted, 52.6% with angina, hypertension and dyslipidemia 100%. In the first stage the nutritional treatment reduced body weight, WC, BMI and PP and insulin concentrations, HbA1C, HOMA-IR and QUICK, without changing the other parameters. In the second stage of the study, it was observed that the GDOC maintained the reduction of body mass, BMI, WC, with a significant difference between groups for DC (-2.1 +/- 2,7 cm; p < 0.01). In addition, there was an increase in HDL-C concentrations, Apo A, with significant difference in GD, only for HDL-C (3.1 +/- 7.4 mg/dL; p = 0.02). CONCLUSION: it was observed that the nutritional treatment associated with extra virgin coconut oil consumption reduced the CC and increased HDL-C levels in patients with CAD. PMID- 26545672 TI - IN VITRO AND IN VIVO ANTIOXIDANT ACTIVITY OF BURITI FRUIT (MAURITIA FLEXUOSA L.F.). AB - INTRODUCTION: studies have shown high concentration of monounsaturated fatty acids, carotenoids, polyphenols and ascorbic acid in Buriti fruit (Mauritia flexuosa L.f.). This study evaluated the in vitro and in vivo antioxidant activities of buriti fruit (Mauritia flexuosa L.f.). METHODS: the chemical composition and total phenolic and carotenoid contents of the buriti pulp and the feed rations were determined, and the in vitro antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. Wistar rats (21 days old) were randomly allocated (n=10) into a control groups and experimental groups (feed enriched with buriti pulp). After 60 days, the in vivo antioxidant activity was evaluated through the determination of the catalase activity and non protein sulfhydryl (NPSH) groups in the liver and quantification of malondialdehyde (MDA) in the plasma and tissues. RESULTS: high contents of oleic fatty acids (73.3%), phenolic compounds (192 +/- 0.3 mg/100 g) and carotenoids (23.9 +/- 0.5 mg/100 g) as well as elevated in vitro antioxidant activity were found in the buriti pulp. The enriched diet had higher contents of phenols and carotenoids as well as higher antioxidant activity compared with the standard feed (p < 0.05). There were no differences between the groups regarding catalase activity in the liver and MDA concentrations in the plasma, liver and kidneys. The male rats of the experimental group had higher liver concentrations of NPSH compounds (p < 0.05). CONCLUSION: these results may corroborate the claim that buriti fruit is an antioxidant functional food and support its utilization in a nutritionally balanced diet. PMID- 26545673 TI - PREVALENCE AND FACTORS ASSOCIATED WITH VITAMIN B12 DEFICIENCY IN ELDERLY FROM VICOSA/MG, BRASIL. AB - The prevalence of vitamin B12 nutritional deficiency increases with age and it is particularly common in elderly people. The objective this study was determining its prevalence and the factors associated with this condition in non institutionalized elderly from Vicosa, Minas Gerais State, Brazil. METHODS: a cross-sectional, population-based study was conducted in order to identify the prevalence and the factors associated with vitamin B12 deficiency among the elderly population in Vicosa (MG). Data were collected from August 2011 to June 2012, by means of a household survey and hematological and biochemical tests performed in 340 elderly. RESULTS: the prevalence of vitamin B12 deficiency in this group was 17.4% (95% CI, 13.4% - 21.4%). Cognitive impairment appears to be an important factor related to vitamin B12 deficiency. CONCLUSIONS: the current paper contributes to studies that emphasize some factors that may affect elderly performance in their natural aging process, especially when these factors are associated with cognitive impairment and lead to significant disability and loss of quality of life. Thus, the herein presented results were able to provide more comprehensive knowledge on the relation between B12 deficiency and its impact on this population. They also proved to be relevant for planning public health programs and initiatives that target on this age group. PMID- 26545674 TI - [MALNUTRITION IN THE ELDERLY PATIENT TO HOSPITAL ADMISSION, AN OLD PROBLEM UNSOLVED]. AB - OBJETIVE: to determine the prevalence of malnutrition in patients aged 65 years or more at admission and factors associated with its presence. Analyze excess hospital stay (EHS), economic impact and premature readmission rate associated with hospital malnutrition in elderly patient. MATERIAL AND METHOD: retrospective study conducted at the University Hospital Reina Sofia. All patients aged 65 years or older admitted to internal medicine in 2011. The sample size was calculated taking into account the income of the previous year, and considering a prevalence of malnutrition of 50% with a 95% and included error of 5%. To define the degree of malnutrition nutritional control tool (CONUT), which establishes a score based on albumin, total cholesterol and lymphocyte determination was used. To determine the factors associated with the presence of moderate to severe malnutrition analysis of multivariate logistic regression was performed. For each patient the EHS, premature readmissions and the associated cost to EHS was calculated. A threshold of statistical significance of 0.05 was used for all analyzes and were performed with SPSS v15.0. RESULTS: 310 patients, of whom 54.2% were women were included, the mean age was 80.1 years (SD: 6.8), ranging between 65 and 95 years. Regarding diagnosis at admission 27.4% were respiratory diseases, 22.6% of the circulatory and digestive 11.6%. The median Charlson index was 2.0, found that 36.8% of patients had high comorbidity. The most prevalent chronic diseases were diabetes mellitus (44.2%), chronic kidney disease (25.2%) and dementia (10.6). Regarding the CONUT, 75.8% of patients met the criteria of malnutrition: 42.6% mild, 28.7% moderate and severe 4.5%, of which only 46.6% had some nutritional support during admission. Factors associated with the presence of moderate to severe malnutrition were female gender (OR: 1.7; 95%: 1.1 - 2.8), age over 80 years (OR: 2.0, IC 95%: 1.2 - 3.5), and dementia (OR: 2.4; IC 95%:1.2 - 5.2). No association with comorbidity or with other chronic diseases was found. Regarding the EHS (days) differences between patients with moderate to severe malnutrition (4.7; IC 95%: 2.3 - 7.1) and normally nourished (-0.1; IC 95%: -1.4 1.2) (p = 0.001) were found, but were not for cases of mild malnutrition (1.6, 95%: 0.5-2.8) (p = 0.07).Regarding the rate of premature readmission in malnourished patients was 28/235 (11.9%). The cost associated with EHS / 100 patients was ? 195 479.4 for moderate malnutrition, mild malnutrition ? 73 484.8, and normally nourished patients represented a saving of ? 12 353. CONCLUSIONS: hospital malnutrition in elderly patients remains an unsolved problem, given the high prevalence found, associated to an excess of hospital stay and increased hospital costs, especially in patients with moderate to severe malnutrition. The CONUT is a nutritional screening tool very useful for the speed and validity of their results, and allows detecting patients at risk or nutritional alert without lead to increased costs. PMID- 26545675 TI - CHRONIC ENTERITIS IN PATIENTS UNDERGOING PELVIC RADIOTHERAPY: PREVALENCE, RISK FACTORS AND ASSOCIATED COMPLICATIONS. AB - INTRODUCTION: the radiation of tumours located in pelvic organs can cause mucositis in the bowel. The aim of this study was to determine the prevalence, risk factors, and complications of chronic radiation enteritis in patients who had received pelvic radiotherapy. PATIENTS AND METHODS: cross-sectional study recruiting 150 patients that had been treated with radiation therapy during the year 2008 because of a prostate, cervical, endometrial or rectal cancer. The patients were asked about symptoms related to enteritis, and about changes in body weight and in dietary patterns. Sex, age, treatment modalities, acute enteritis, and type of cancer were considered possible risk factors, and were analysed with univariate and multivariate methods. RESULTS: the study included 100 patients, 84% males, median age 72.3 years. Chronic radiation enteritis was found in 20% of the patients, most of them grade 1 (45%). Furthermore, 10% had lost >= 5 kg of weight, 3% had been hospitalized due to diarrhoea or bowel obstruction, and 11% had changed their diet, mainly by removing vegetables, legumes and pastry. Male gender, age, previous acute radiation enteritis, and chemotherapy were associated with chronic enteritis, but only chemotherapy remained independently related to bowel toxicity after multivariate analysis (OR = 3.59 [95% CI 1.20-10.73]). CONCLUSION: chronic enteritis is common among patients treated with pelvic radiotherapy, especially if chemotherapy is associated. The complication rate is low, but a significant number of patients change their usual diet in order to prevent symptoms. PMID- 26545676 TI - [PHYSICAL ACTIVITY LEVELS, PHYSICAL FITNESS AND SCREE TIME AMONG CHILDREN AND ADOLESCENTS FROM BOGOTA, COLOMBIA]. AB - OBJECTIVE: to investigate the association between objective measures of physical activity levels, physical fitness and screen time in Colombia children and adolescents from Bogota, Colombia. METHODS: a sample of 149 healthy Colombian youth, children and adolescents (9-17.9 years old) participated in the study. Physical activity level was assessed over 7 days using an accelerometer. Weight, height, waist circumference, hip waist, subscapular/ triceps skinfold thicknesses and self-reported screen time (television/internet and videogame-viewing time) were measured. Aerobic capacity, handgrip strength, standing broad jump, vertical jump, speed/agility and flexibility were used as indicators of physical fitness. RESULTS: in girls with a high level of physical activity had favorable aerobic capacity (r = 0.366) and inverse relationship with subscapular/triceps skinfold thicknesses (r = -0.257) and (r = -0,237) p < 0.05, respectively. In boys, vigorous physical activity were associated with higher values of flexibility (r = 0.277) and aerobic capacity (r = 0.347), p < 0.05. Finally, the participants who watched 2 h or less of television per day showed 1.81 times (95%CI 1.401 to 2.672) that met physical activity guidelines. CONCLUSIONS: the healthy Colombian youth who reported moderate to vigorous objective measures of physical activity levels, presented higher levels in physical fitness especially in aerobic capacity and flexibility and lower values in subscapular/triceps skinfold thicknesses. PMID- 26545677 TI - A SHORT-TERM CIRCUIT RESISTANCE PROGRAMME REDUCED EPICARDIAL FAT IN OBESE AGED WOMEN. AB - INTRODUCTION: this study was conducted to ascertain the effects of resistance circuit training on epicardial adipose tissue (EAT) in obese aged women. A secondary objective was to assess muscle damage induced by supervised resistance training to confirm the intervention program was effective and safe. METHODS: in the present interventional study, a total of 48 obese aged women were recruited from the community. Twenty-four of them were randomly assigned to perform a 12 week resistance circuit training programme, 3-days per week. This training was circularly performed in 6 stations: arm curl, leg extension, seated row, leg curl, triceps extension and leg press. The Jamar handgrip electronic dynamometer was used to assess maximal handgrip strength of the dominant hand. Two experienced observers assessed EAT by transthoracic two-dimensional echocardiography. Lastly, serum samples were analysed using one-step sandwich assays for creatine kinase activity (CK) and myoglobin (MB) concentration. RESULTS: as was hypothesized, resistance training significantly reduced EAT thickness (8.4 +/- 1.0 vs. 7.3 +/- 1.3 mm; p = 0.014; d = 0.76) in the experimental group. Resistance training induced no significant changes in markers of muscle damage such as CK (181.6 +/- 36.9 vs. 194.2 +/- 37.8 U/l; p = 0.31) and MB (62.4 +/- 7.1 vs. 67.3 +/- 7.7 ng/ml; p = 0.26). No significant changes in any of the tested outcomes were found in the control group. CONCLUSION: resistance training reduced EAT in aged obese women. A secondary finding was that the training program was effective and safe. While current results are promising, future studies are still required to consolidate this approach in clinical application. PMID- 26545678 TI - [EFFECTS OF VOLUNTARY INTAKE OF FLUIDS (WATER AND SPORTS DRINK) IN AMATEUR MOUNTAIN RUNNERS]. AB - INTRODUCTION: 21 K and 1 000 m ascent trail-running races can be dangerous if an appropriate liquid replacement isn't maintained. OBJECTIVES: know trail-runners level of dehydration and assess the differences between ad libitum water (CcA) and sport drink (CcB) hydration after a trail running race. METHODS: 18 subjects, mean age 31.9 (+/-2.8) and %MG 10.53 (+/-2.8), completed CcA or CcB. CcA and CcB effects on Weight (P), Fat Mass (MG), Glucose (GL), Lactate (LT), Systolic (TAS) and Diastolic Arterial Tension (TAD), Heart Rate (PPM) and Tympanic Temperature (Ta) were assessed. All measurements were taken at the start (T1) and the finish (T2) of each race. A Friedman ANOVA test was used to calculate the effect of CcA and CcB on each variable. Differences between race time (TC), % bodyweight loss (%PP) and liquid ingestion (LI) were assessed with a Wilcoxon test. All statistical analysis were conducted with SPSS version 20.0 (IBM, Somers, NY, USA). RESULTS: mean %PP was 2.967 (+/- 0.969) and 2.883 (+/- 0.730) for CcA and CcB respectively. No significant differences were found between %PP and LI (p > .05) between races. Significant changes were found in P, %MG, GL, L, TAS and PPM between T1 and T2 in CcA condition. While only significant changes in P and PPM were stabilised between T1 and T2 in CcB condition. CONCLUSIONS: neither water or sport drink ingestion avoid trail-runners to reach a dehydrated state. However, dehydration effects seems to be more serious when only water is ingested. PMID- 26545679 TI - BODY COMPOSITION AND SOMATOTYPE OF PROFESSIONAL AND U23 HAND BASQUE PELOTA PLAYERS. AB - INTRODUCTION: there is hardly any reference in scientific literature regarding anthropometric characteristics, body composition and somatotype of hand Basque pelota players (pelotaris). OBJECTIVES: the aim of this research was to analyze and compare the anthropometry features and body composition of professional pelotaris and under-23 (U23) pelotaris, to create an anthropometric profile of this sport. METHODS: the participants were ten U23 pelotaris, and eight professional pelotaris. Anthropometric measurements were taken following the International Society of Advancement of Kinanthropometry (ISAK) protocol. Fat mass (FM) was calculated using the Yushasz equation modified by Carter and muscle mass (MM) using Lee equation. For the somatotype components, the Carter y Heath equation was applied. The hydration level (kg of body water) of the players was measured with a four-pole kind bioelectrical impedance (BIA) analyzer. Spss was used for the statistical analysis. RESULTS: professional pelotaris have significantly lower FM (p < 0.05) and lower sum of 4, 6 and 8 skinfolds (p = 0.001), higher MM (p = 0.015), and a less endomorphic somatotype (p < 0.001) than U23 pelotaris. Professionals have a greater amount of body water (p = 0.001) and a larger bistyloid diameter (p = 0.014). Professional pelotaris have a morphotype characterized by a low FM 8.9 +/- 1.1% and medium MM 47 +/- 1.7%, height of 183.0 +/- 7.1 cm and BM of 85.9 +/- 7.6 kg. CONCLUSION: The main results of the present study show that non-modifiable anthropometric features by training (e.g. height, arm span and wrist breadth) are important to become a professional pelotaris. Moreover, training and diet related features have been showed to be better in professional pelotaris (low FM, higher MM and high body water amount) than U23 pelotaris. PMID- 26545680 TI - ASSESSMENT OF SOMATIC MATURATION OF VENEZUELAN ADOLESCENTS. AB - INTRODUCTION: beginning of adolescence comprises important physical modifications, which affects growth and changes in body composition, therefore it is important to consider maturation assessment. OBJECTIVE: to develop a non invasive method to assess maturity status in Venezuelan adolescents from peak height velocity (PHV) by means of anthropometric variables in a cross-sectional sample. METHODS: data comprised 681 Venezuelan adolescents 9 up to 18 years of age. Mirwald equation was applied to derived PHV. Regression analysis was used in order to build a model for Venezuelan sample as well as, ROC curves to assess sensitivity and specificity of anthropometric variables. RESULTS: the predictive equations for both sexes, exhibited a high determination coefficient (< 0.99) and a minimal estimation error (0.06). Mean decimal age at categories of PHV obtained by both equations: criterion and model, were very similar (13.27 vs. 13.39) for boys, and (11.62 vs. 11.77) for girls. Bland-Altman plot showed a tight concordance between the two equations and all anthropometric indices, exhibited high area under the curve > 0.75, specially sitting height. DISCUSSION AND CONCLUSION: in Venezuela, there is little work based on longitudinal studies of the maturation status. Giving the difficult faced in the longitudinal studies recent works have been used cross-sectional methodology in the assessment of the somatic maturation, both in non athletic and athletic populations. This study provides predicting equations for the assessment of the somatic maturation adjusted to Venezuelan population developed from Mirwald equation, which may be used to aid in evaluation of nutritional and general health, as well as, a reduction of risks associated with miss-classification for chronological age. PMID- 26545681 TI - [BODY COMPOSITION PARAMETERS AND RELATIONSHIP WITH THE MAXIMAL AEROBIC POWER IN RECREATIONAL CYCLISTS]. AB - OBJECTIVE: the aim of this study is to relate body composition parameters on performance in recreational cyclists using fat mass (MG), total muscle mass (MM) and the appendix of the lower extremity (MMEI) with maximal aerobic power (PAM). METHODS: 11 male cyclists (27.7 +/- 4.5 years; 72.4 +/- 12.4 kg; 173.2 +/- 6.7 cm.) were recruited. The anthropometric measurements were performed according to the protocols of the International Society for the Advancement of Kineanthropometry (ISAK) and testing of PAM were held following a ramp protocol, which began with an initial load of 150 W and then increments 30 W at 1-minute intervals until exhaustion. RESULTS: there is dependence between variables and the VO2max MG that correlate negatively and significantly (p < 0.05). MM respect to variables and the VO2max significantly negatively correlated (p < 0.05). In correlation with the PAM, MMEI it can be seen a positive and significant correlation (p < 0.01) indicating that individuals who have greater muscle component in the lower limbs (EEII) are able to generate more power. CONCLUSIONS: we conclude that the results obtained, both the MG and the MM are not a good reference as performance parameters regarding the VAM. The MMEI was the only parameter that showed a positive relationship as a marker of performance in recreational cyclists. PMID- 26545682 TI - [DIFFERENCES IN PHYSICAL ACTIVITY AND IN PHYSICAL CONDITION BETWEEN SCHOOL AGE STUDENTS OF TWO PUBLIC CURRICULUM PROGRAMS IN BOGOTA, COLOMBIA]. AB - During the past five decades there has been an increased in the prevalence of obesity and over weight, also in physical inactivity and /or low cardiorespiratory fitness within the population in school age from diverse regions of the planet, including Bogota-Colombia. The general objective of this study was to compare the physical condition and the levels of physical activity from students who belonged to two curriculum programs of the Public Schools Network from Bogota, one of which includes two sessions per week, each session of 90 minutes of physical activity. We developed a research of unlike cross sectional groups. There were 178 children evaluated from the regular curriculum and 170 kids belonging to the program 40 x 40. The physical condition was evaluated applying the protocol of high priority from the ALPHA -Fitness test Battery. The weight, height, body mass index, the waist circumference, the standing long jump, the handgrip in both hands and the motor fitness 20 meter shuttle run test were developed under standardized conditions. The Global School Health Survey (GSHS) was used to evaluate the levels of AF. No significant statistical differences were founded between P-40x40 and the regular curriculum regarding: weight, height, the body mass index, the waist circumference, the handgrip in both hands and the explosive strength in lower limbs. Nevertheless the cardiorespiratory fitness was significantly lower within de P-40x40. In conclusion the participation in the curricular program 40 x 40 was not associated with better levels of physical condition. PMID- 26545683 TI - [TRAINING HABITS OF FEMALE INTERNATIONAL ELITE MOTORCYCLIST]. AB - INTRODUCTION: there are few studies about the professional Motorcycle. OBJECTIVE: the aim of this work is to analyze the training habits of 18 female motorcyclists of international level and to know the history about the practice of sport, the medical history of injuries and their ailments. METHOD: data collection was performed using a 20-item instrument designed for women riders. It was collected about age, performance level of motor sport, frequency, duration and type of training, injuries and muscle pain. RESULTS: the results show that despite a few hours of training, the riders conceived that they have a normal or even a good physical condition. Particularly striking are the absence of mental or tactical training and the lack of medical checks and reviews. Positive correlations were found in the variables of pain. CONCLUSIONS: the motorcycling requires a specific, controlled and planned training and medical monitoring and dietetic through multidisciplinary team training. PMID- 26545684 TI - [PRESSURE ULCER: INCIDENCE AND DEMOGRAPHIC, CLINICAL AND NUTRITION FACTORS ASSOCIATED IN INTENSIVE CARE UNIT PATIENTS]. AB - Pressure ulcer (PU) is a lesion in the skin and/or underlying tissue, usually over bony prominences caused by pressure and / or shear associated. Although preventable, is still very prevalent, and pointed out that multiple factors are involved in its etiology. OBJECTIVE: to identify the incidence of pressure ulcers, clinical and nutritional factors associated in patients admitted to the Intensive Care Unity (ICU) of a university hospital. METHODS: a prospective, observational study, with patients admitted to an ICU from June to November 2014. The UP was determined by inspection body three times a week during the morning bath, based on the characteristics established by the National Pressure Ulcer Advisory Panel, 2014. We collected demographic, clinical, biochemical and nutritional. The Braden Scale was used to verify individuals at risk of PU development. RESULTS: the sample consisted of 51 patients with a mean age of 57.7 (+/- 16.4) years. There was an incidence of UP 52.9%, and the factors associated with its development were: use of vasoactive drugs (p = 0.029), length of hospital stay > 10 days (p <= 0.001) and absence of anemia (p = 0.011). CONCLUSION: the high incidence of UP highlights the vulnerability of patients in intensive care. Although characterized by being a multifactorial condition only the use of vasoactive drugs, length of hospital stay and the absence of anemia were associated with the appearance of refs. Nutritional and clinical factors often related to trauma were not associated with their development. PMID- 26545685 TI - CUTOFF POINT OF THE PHASE ANGLE IN PRE-RADIOTHERAPY CANCER PATIENTS. AB - INTRODUCTION: malnutrition is a common complication for cancer patients. The phase angle (PA), direct measurement of bioelectrical impedance analysis (BIA), has been considered a predictor of body cell mass and prognostic indicator. Cutoff points for phase angle (PA) associated with nutritional risk in cancer patients have not been determined yet. OBJECTIVES: assess the possibility of determining the cutoff point for PA to identify nutritional risk in pre radiotherapy cancer patients. METHODS: sample group: Patients from both genders diagnosed with cancer and sent for ambulatory radiotherapy. VARIABLES STUDIED: body mass index (BMI), percentage of weight loss (% WL), mid-arm circumference (MAC), triceps skinfold thickness (TST), mid-arm muscle circumference (MAMC), mid arm muscle area (MAMA), score and categorical assessment obtained using the Patient-Generated Subjective Global Assessment (PG-SGA) form, PA and standardized phase angle (SPA). Kappa coefficient was used to test the degree of agreement between the diagnoses of nutritional risk obtained from several different methods of nutritional assessment. Cutoff points for the PA through anthropometric indicators and PG-SGA were determined by using Receiver Operating Characteristic (ROC) curves, and patient survival was analyzed with the Cox regression method. RESULTS: the cutoff points with the greatest discriminatory power were those obtained from BMI (5.2) and the categorical assessment of PG-SGA (5.4). The diagnosis obtained using these cutoff points showed a significant association with risk of death for the patients in the sample group. CONCLUSION: we recommend using the cutoff point 5.2 for the PA as a criterion for identifying nutritional risk in pre-radiotherapy cancer patients. PMID- 26545686 TI - [TOXIC RISK ASSESSMENT OF FLUORIDE PRESENCE IN BOTTLED WATER CONSUMPTION IN THE CANARY ISLANDS]. AB - INTRODUCTION: fluorine, as an hormetin, is necessary in the organism to avoid caries; but large amounts can produce toxic side effects such as dental fluorosis or skeletal fluorosis. Thus, it is important not to exceed chronically the RDIs (Recommended Daily Intakes) per each age and sex range. It is assumed that the main fluoride source is water. OBJECTIVES: to establish fluoride concentrations at certain bottled water brands being consumed in the Canary Islands for renovating the outdated data, and to evaluate the subsequent toxic risk. METHOD: 25 samples have been used from 7 different registered and commercialized brands, being analyzed by a potentiometer with a fluoride ion selective electrode. RESULTS: all analyzed water brands satisfied quality criteria according to the Spanish law, no one could be considered "fluorinated water" and all of them could be used to prepare baby food. Moreover, according to the recommended daily water intake by the EFSA per each age range, no water analyzed brand could exceed the RDI for no one over 4 years old. CONCLUSIONS: the bottled waters that are produced in the Canary Islands have similar fluoride concentrations than those that are produced in the Peninsula (all of them have a data range between 0.24 and 0.62 mg/L). The individuals who have more water restrictions are those under 1 year old; but in any case, while the child is growing up, the levels of fluoride consumption can be higher (until 19 years old) and therefore the water brands variety that can be drunk, without exceeding the RDI, is also higher. In some places in the Canary Islands, it would be advisable to consume bottled water in place of tap water. PMID- 26545687 TI - EFFECTS OF FOOD AND DRINK INGESTION ON BODY COMPOSITION VARIABLES OF ABDOMINAL BIOELECTRICAL IMPEDANCE. AB - OBJECTIVE: to know the changes in trunk fat and visceral fat level determined by abdominal bioelectrical impedance (BIA) as well as other anthropometric measures related to the central or abdominal fat after the ingestion of a lunch. METHODS: the experimental study was conducted to assess a longitudinal intervention descriptive study. PARTICIPANTS: 21 subjects (10 male and 11 female), volunteers who have access to a medical assessment, with an age of 74 +/- 13.43 years. MEASUREMENTS: Maximal waist circumference in standing position, waist circumference at navel level in supine position and sagittal abdominal diameter (SAD). In the same position trunk fat and visceral fat level by abdominal bioelectrical impedance analysis with Tanita AB-140 (ViScan) were obtained before and after meal. RESULTS: anthropometric measures as waist circumference in supine position and SAD did not show significant differences (P > 0.05), after food ingestion, except for a significant increase of the maximal waist circumference in standing position (P < 0.05). In addition trunk fat and visceral fat ratio did not change (P > 0.05). The percentage changes of the measures were less than 2% for waist circumference in standing position, waist circumference by Viscan, sagittal abdominal diameter and trunk fat and 5.9% for visceral fat ratio. CONCLUSIONS: the effects on trunk fat and visceral fat ratio by abdominal bioelectrical impedance are minimal after the ingestion of a portion of food and drink, although it is always recommended to do it in fasting conditions. PMID- 26545688 TI - CONSTRUCTION AND EXPRESSION OF DERMATOPHAGOIDES PTERONYSSINUS GROUP 1 MAJOR ALLERGEN T CELL FUSION EPITOPE PEPTIDE VACCINE VECTOR BASED ON THE MHC II PATHWAY. AB - Backgound and aims: Dermatophagoides peteronyssinus is one of the important house dust mites responsible for allergic asthma that can be tentatively managed by specific immunotherapy. The present study was to construct a vector encoding T cell epitopes of major allergen group 1 of Dermatophagoides pteronyssinus as a vaccine delivered by MHC class II pathway. METHODS: the nucleotide sequences of the 3 target genes were synthesized, including TAT, IhC and the recombinant fragment of Der p 1 encoding 3 T-cell epitopes. After amplification of the 3 target fragments by PCR and digestion with corresponding restriction endonucleases, the recombinant gene TAT-IhC-Der p 1-3T was ligated using T4 DNA ligase and inserted into the prokaryotic expression vector pET28a(+) to construct the recombinant plasmid pET- 28a(+)-TAT-IhC-Der p 1-3T, which was confirmed by digestion with restriction endonucleases and sequencing. The recombinant vector was transformed into E. coli strain BL21 (DE3) and induced with IPTG, and the induced protein TAT-IhC-Der p1-3T was detected by SDS-PAGE. After purification, the recombinant protein was confirmed by Western blotting and its allergenicity tested using IgE-binding assay. RESULTS: the recombinant plasmid pET-28a-TAT IhCDer p1-3T was successfully constructed as confirmed by restriction endonuclease digestion and sequencing, and the expression of the recombinant protein TAT-IhC-Der p1-3T was induced in E. coli. Western blotting verified successfull purification of the target protein, which showed a stronger IgE binding ability than Der p1. CONCLUSION: we successfully constructed the recombinant expression vector pET-28a-TAT-IhC-Der p1-3T expressing a T-cell epitope vaccine delivered by MHC II pathway with strong IgE-binding ability, which provides a basis for further study on specific immunotherapy via MHC class II pathway. PMID- 26545689 TI - MICROBIOLOGICAL ASSESSMENT OF LETTUCE SALADS AND ANTIMICROBIAL RESISTANCE OF STAPHYLOCOCCUS SPP. AB - INTRODUCTION: self-service restaurants in which food is served ready to be consumed are liable to have some products contaminated by pathogenic microorganisms causing food-transmitted diseases. AIM: evaluates the microbiological quality of lettuce salads in restaurants in Pelotas RS Brazil by counts of thermo-tolerant coliforms, E. coli, Staphylococcus spp. and detection of Salmonella spp. Antimicrobial resistance of Staphylococcus spp. isolates are also assessed. METHODS: thirty-six samples of lettuce salads were collected from nine restaurants and thermotolerant coliforms, Escherichia coli and Staphylococcus spp. were quantified, coupled to a research on Salmonella spp., following methodology by the Bacteriological Analytical Manual. Staphylococcus spp. isolates underwent antimicrobial resistance test by the disc-diffusion method. RESULTS AND DISCUSSION: results showed that 61.1% of the salad samples contained more thermotolerant coliforms than allowed by Brazilian legislation and E. coli was confirmed in 5.6% of the samples. Positive and negative coagulase Staphylococcus occurred respectively in 5.6% and 77.8% of isolates, but no sample had Salmonella spp. Further, 56.7% of the thirty isolates of Staphylococcus spp. tested were resistant to penicillin; 46.7% to oxacillin; 26.7% to erythromycin and 23.3% were multi- resistant. CONCLUSION: inadequate quality of the salad was due to pathogenic microorganisms, while Staphylococcus spp. isolates had a high percentage of antimicrobial resistance. PMID- 26545690 TI - [CITY VS. COUNTRYSIDE: WHERE DO YOU EAT BEST AND HEALTHIEST?]. AB - INTRODUCTION: bearing in mind the influence of the environment on the individuals and their choices and behaviours in general and particularly with respect to food, it might be interesting to explore whether eating habits are better or healthier in rural areas than in urban ones. OBJECTIVE: to analyse the perception of the level in which eating habits could be considered better or worse, more or less healthy, in rural and urban areas. METHOD: 281 students (18.37 +/- 6.28 years) volunteered participated in the study completing an ad hoc questionnaire designed to measure the characteristics attributed by the participants to the rural and urban eating habits. RESULTS: 49.50% of the participants considered that food is better in rural areas, 8.50% in urban contexts and 42% equally in both rural and urban areas; 80.42% responded that food is healthier in rural areas and 19.57% in urban areas. In addition, 85.10% of the participants coming from rural families considered that food is healthier in the country and the same applies to 75.80% coming from urban families. DISCUSSION AND CONCLUSIONS: the perception about what is healthy is not uniform. From a general point of view it seems that eating better is not the same than eating healthier. The idea of eating better not always is synonymous of eating healthy from a medical nutritional point of view. This difference could make it difficult to spread the idea of a healthy way of eating to the general population. PMID- 26545691 TI - EFFECT OF ANTIOXIDANT POTENTIAL ON SEVERITY OF CIRRHOSIS IN HUMANS. AB - BACKGROUND/AIMS: to examine the relationship between the antioxidant potential and severity parameters of cirrhosis in humans. METHODS: fifteen patients with hepatic cirrhosis (nine subjects - Child group B, and six subjects - Child group C) and nine control subjects were enrolled in the study. The main criteria taken into account to characterize the diagnosis of cirrhosis and its complications were the AST: ALT ratio, AST to platelet ratio index, Bonacini score, Meld score and Child classification. Those parameters were determined based on laboratory results and patient's clinical records. Se, Zn, ascorbic acid (AA) levels and oxidative stress parameters were measured in blood samples of cirrhotic patients. RESULTS: the analysis of plasma levels of Se and AA showed low concentrations in cirrhotic patients compared with control subjects (P < 0.05). Though, there was a positive correlation between plasma of Se and severity parameters of cirrhosis in patients of Child group B and C. In the activity of the antioxidant enzymes only catalase was lower in patients of Child group C compared with control group. CONCLUSION: we found low plasma levels of Se and AA among cirrhotic patients. However, is not clear why selenium levels tend to increase with the severity of liver cirrhosis. PMID- 26545692 TI - [CONSUMPTION OF READY-TO-EAT CEREAL IS INVERSELY ASSOCIATED WITH BODY MASS INDEX IN 6-13 YEARS OLD CHILEAN SCHOOLCHILDREN]. AB - BACKGROUND AND AIMS: childhood obesity in Chile is a serious problem with the prevalence continuing to increase over the last decade, despite all governmental efforts to diminish it. Studies indicate that the consumption of certain foods may help to control body weight. The objective of this study was to evaluate the relationship between ready-to-eat cereals (RTEC), body mass index and nutritional intake of macronutrients and micronutrients in school children from Santiago, Chile. METHODS AND RESULTS: the study included 1 477 children aged 6-13 years who were evaluated by trained nutritionists. Weight, height and waist circumference were measured and a 24-hour recall questionnaire was administered in which the hours spent watching TV were also recorded. Overall, 32% of boys and 28 % of girls were overweight but the difference between them was not significant. All children, regardless of sex, showed a significant inverse relationship between amounts of RTEC consumed and body mass index (BMI). Those girls that consumed higher amount of RTEC had a reduced waist circumference than those that had a lower intake. A high consumption of RTEC in all children was related to a higher intake of calories, proteins, carbohydrates, calcium and zinc and to a lower intake of calories from fat. RTEC consumption was also associated with lower risk of being overweight/obese. CONCLUSION: this study identifies RTEC intake as a potential indicator of a healthy diet. Controlled interventions are necessary to isolate the effect of RTEC consumption from other participating factors. PMID- 26545693 TI - [BEHAVIOR OF HEMOGLOBIN CONCENTRATION, HEMATOCRIT AND OXYGEN SATURATION IN COLOMBIAN UNIVERSITY POPULATION AT DIFFERENT ALTITUDES]. AB - INTRODUCTION: the development of this research is base on the growing interest in understanding the adaptations to chronic hipoxia mainly in the range of intermediate altitudes (1 500-3 000 m.s.n.m) and the need to establish parameters of normality in the variables [Hb], Hct and SO2 for diagnostic and characterization of the population purposes. OBJECTIVE: to analyze the behavior of the [Hb], Hct and SaO2 at different intermediate altitudes (970 m.s.n.m, 1 520 m.s.n.m, 1 728 m.s.n.m, 1 923 m.s.n.m, 2 180 m.s.n.m and 2 600 m.s.n.m) in order to contribute to the knowledge of the high altitude physiology and the clinical field to support the diagnosis of anemia. METHODS: clinically healthy subjects with low levels of physical activity and food consumption report containing iron. Total of 264 participants of both genders between 18 and 30 years. The blood samples were collected from the antecubital vein and the earlobe and analyzed in a radiometer. A non-parametric statistical analysis was performed. RESULTS: with increasing of altitude, [Hb] and Hct values were increased while the SO2 decreased. Men showed higher values than women in [Hb] and Hct, related to lower values of SO2 than women. DISCUSSION: a threshold variable was not found, perhaps because of the small distance between the altitudes. The values reported were similar but not identical to other studies. This difference could be explained by genetic diversity among populations. CONCLUSIONS: this study allows for the first values of characterization of the study population. All altitudes were above the cutoff for the diagnosis of anemia ([Hb] 12 g/dl). PMID- 26545694 TI - [ASSOCIATION BETWEEN DIETARY GLYCEMIC INDEX AND GLYCEMIC LOAD AND INTIMA MEDIA THICKNESS IN A POPULATION AT HIGH CARDIOVASCULAR RISK: A SUBGROUP ANALYSIS IN THE PREDIMED TRIAL]. AB - BACKGROUND: increased carotid intima-media thickness (IMT) is a marker of atherosclerosis and a predictor of future cardiovascular events. Although a beneficial effect of Mediterranean diets, in particular, enhanced with virgin olive oil and nuts, on longitudinal changes in IMT has been reported, the association between carbohydrates and the development of atherosclerosis is still unclear. OBJECTIVE: to assess the association between glycemic index (IG) and glycemic load (CG) of the diet and intima media thickness (GIMC) in a population at high cardiovascular risk with no clinical symptoms. METHODS: one hundred eighty seven participants of the PREDIMED-NAVARRA center (PREDIMED means in Spanish "PREvencion con DIeta MEDiterranea") were randomly selected to undergo baseline and 1-year measurement of GIMC. Dietary information was collected at baseline and yearly using a validated 137-item food frequency questionnaire. Participants were categorized into four groups of energy-adjusted IG and CG intake. Multivariate analysis models (ANCOVA) were used to study the association between dietary IG and CG and GIMC and its changes. RESULTS: in our study we found no significant association between IG or CG and GIMC at baseline or after one year. PMID- 26545695 TI - TREATMENT OF SUBCLINICAL HYPERTHYROIDISM: EFFECT ON BODY COMPOSITION. AB - BACKGROUND: subclinical hyperthyroidism (SHT) is associated with harmful effects on cardiovascular system, bone metabolism and progression to clinical hyperthyroidism. Loss of weight is a common fact in patients with clinical hyperthyroidism and of particular relevance in elderly patients. OBJECTIVE: to assess changes in body composition after radioiodine therapy for SHT due to toxic nodular goiter. SUBJECTS AND METHODS: prospective controlled cohort study. Patients with persistent SHT due to toxic nodular goiter were purposed to receive treatment with radioiodine (treatment group) or to delay treatment until the study was over (control group). All treated patients received 555 MBq of 131I. Body composition (lean mass, fat mass and bone mineral content) was determined by dual-energy X-ray absorptiometry (DEXA) at baseline and 12 months after. RESULTS: twenty-nine patients were studied (age 69.5 +/- 11.5; 75.9% women; BMI 27.1 +/- 5.7 kg/m2; serum thyrotropin (TSH) 0.20 +/- 0.21 MUUI/mL; serum free thyroxine (T4) 1.01 +/- 0.19 ng/dL), 17 belonging to the treatment group and 12 to the control group. Study groups were comparable, although there was a trend for the treatment group to have more fat mass. No longitudinal changes in body composition were noted in either group, except for a trend to gain fat mass. However, when individuals with age > 65 years were selected, only patients who received radioiodine therapy showed a significant increase in body weight (from 64.1 +/- 10.0 to 66.9 +/- 9.2 kg), BMI (from 27.3 +/- 4.8 to 28.7 +/- 4.5 kg/m2), fat mass (from 26.1 +/- 8.5 to 27.8 +/- 7.9 kg), lean mass (from 36.3 +/- 0.4 to 37.4 +/- 0.4 kg) and skeletal muscle mass index (SMI) (from 6.0 +/- 0.6 to 6.3 +/ 0.6 kg/m2). CONCLUSIONS: treatment of SHT has impact on body composition in subjects older than 65 years. Weight gain reflects increases in fat and, more interestingly, in lean mass. PMID- 26545696 TI - [FOOD SOURCES OF SODIUM: ANALYSIS BASED ON A NATIONAL SURVEY IN COLOMBIA]. AB - A high sodium intake is an independent risk factor for Cardiovascular diseases CVD-. Thus, a strategy to reduce blood pressure and CVD risk throughout reducing sodium intake is promoted worldwide. In order to design an adequate strategy, it is important to identify the main sources of sodium in food, which has been evaluated mainly in developed countries. OBJECTIVES: to identify foods that provide sodium in Colombians diet, based on data from the National Nutritional Survey -ENSIN-. Furthermore, to determine sodium amount intake from foods. METHODS: data obtained by 24 hours recall (R24h) from 39 413 apparently healthy, non-pregnant population between 2-64 y old population were analyzed. Food groups source of sodium and sodium were determined. RESULTS: 1 274 food were reported by R24h. 95 foods contributed with 72% of total sodium from foods and were divided into 12 groups. The mayor sodium source in the diet was bakery products (30.5%). Average and median sodium intake without salt addition were: 816.4 +/- 474.1 and 721.0 mg/d variable (RQ = 476.0 to 1051.0)mg/d, respectively. Sodium intake from food was higher in men (784.0 mg/d; RQ = 511.0 to 1156.0) than in females (665.0 mg/d; RQ = 448.0 to 953.0); p < 0.001. CONCLUSION: the present study identified the main sources of sodium in Colombians diet. Based on this analysis it is important to prioritize strategies in some groups, especially bakery products. It is also necessary to consider geographical area to implement a relevant strategy. PMID- 26545698 TI - [IS IT USEFUL TO USE THE BODY MASS INDEX TO ASSESS OBESITY IN MUSCULAR PEOPLE?]. PMID- 26545697 TI - [PROPOSAL FOR A NEW FORMULA FOR ESTIMATING RESTING ENERGY EXPENDITURE FOR HEALTHY SPANISH POPULATION]. AB - INTRODUCTION: although there are precise and accurate techniques for estimating resting energy expenditure, like the indirect calorimetry (IC), daily practice needs faster, easier and cheaper methods as the predictive equations. OBJECTIVE: the aim of the study was to develop a new predictive equation for estimating resting energy expenditure (REE) for healthy Spanish population. Methods: the REE of 95 healthy normal weighted volunteers was determined by indirect calorimetry (IC). The new equation was obtained by multiple lineal regression by using the analytical criteria of the Cp of Mallows and the adjusted R2. Then, the behavior of the new formula was studied in a group of overweight volunteers through the intraclass correlation coefficient (ICC) and Bland-Almand plots. The level of signification was reached at p < 0,05. RESULTS: the average age was 42 years (range: 2.0-63.2). Mean REE determined by IC was 1 589.1 kcal/d (312.0). The selected equation was: [y = 1 376.4 - 308 Sex (M = 0; W = 1) + 11.1 Weigh (kg) - 8 Age (years)] (R2: 0.68; EE: 175.95). The ICC between the new equation and the IC in normal weighted subjects was 0.901 (95%CI: 0.851 - 0.934). The new formula showed a good level of agreement in the overweight group (ICC: 0.880; 95%IC: 0.772 - 0.937). CONCLUSIONS: we propose a new predictive equation for estimating the REE for healthy Spanish population which has an easy application and includes sex, age and weigh. The selected equation shows an adequate behavior in overweight subjects too. PMID- 26545699 TI - [PERFORMANCE OF ENTERO-INSULAR AXIS IN AN ATHLETIC POPULATION: DIET AND EXERCISE INFLUENCE]. PMID- 26545700 TI - Comment on Quail et al.: The effect of cloth stoma covers on tracheal climate of laryngectomy patients. PMID- 26545702 TI - Methodologic quality assessment of red blood cell transfusion guidelines and the evidence base of more restrictive transfusion thresholds. AB - BACKGROUND: Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS: Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (<6, <7, or <8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence. RESULTS: The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base. CONCLUSION: Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds. PMID- 26545701 TI - When Patients Write the Guidelines: Patient Panel Recommendations for the Treatment of Rheumatoid Arthritis. AB - OBJECTIVE: How best to involve patients in the development of clinical practice guideline (CPG) recommendations is not known. We sought to determine the feasibility and value of developing CPG recommendations based on a voting panel composed entirely of patients, with the ultimate goal of comparing the patients' recommendations to ones developed by a physician-dominated voting panel on the same clinical questions. METHODS: Ten patients with rheumatoid arthritis completed 8 hours of training on evidence-based medicine and guideline development. They constituted a voting panel and, with 2 American College of Rheumatology staff with expertise in CPG development and a physician facilitator, subsequently met at a face-to-face meeting to develop recommendations. They applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to formulate recommendations on 18 questions for which there was evidence warranting moderate or high confidence. RESULTS: The patient panel developed recommendations for 16 of the 18 questions; for the other 2, the panel thought there were insufficient data to support a recommendation. For 13 of the 16 questions, the patient panel recommended the same course of action as did the physician-dominated panel. Differences were due to how the 2 panels valued the balance between benefits and harms. CONCLUSION: Patient and physician-dominated panels developed the same recommendations for most questions for which there was evidence warranting moderate to high confidence. Additional experiences are necessary to advance the evidence necessary to determine what panel composition is optimal to produce the best guidelines. PMID- 26545703 TI - A 2D Polychloride Network Held Together by Halogen-Halogen Interactions. AB - In a eutectic mixture of two ionic liquids, we have synthesized and crystallized the new polychloride compound [Et4 N]2 [(Cl3 )2 ?Cl2 ] that exhibits a periodic 2D polychloride network acting as an anionic layer. Based on its low melting point and vapor pressure, this compound can be described as a room-temperature ionic liquid. The compound was fully characterized by IR and Raman spectroscopy as well as single-crystal X-ray structure determination. The characterization was complemented by solid-state quantum-chemical calculations confirming the results of the experimental work. PMID- 26545704 TI - To RCT or not to RCT? The ongoing saga of randomised trials in quality improvement. PMID- 26545705 TI - Lost information during the handover of critically injured trauma patients: a mixed-methods study. AB - BACKGROUND: Clinical information may be lost during the transfer of critically injured trauma patients from the emergency department (ED) to the intensive care unit (ICU). The aim of this study was to investigate the causes and frequency of information discrepancies with handover and to explore solutions to improving information transfer. METHODS: A mixed-methods research approach was used at our level I trauma centre. Information discrepancies between the ED and the ICU were measured using chart audits. Descriptive, parametric and non-parametric statistics were applied, as appropriate. Six focus groups of 46 ED and ICU nurses and nine individual interviews of trauma team leaders were conducted to explore solutions to improve information transfer using thematic analysis. RESULTS: Chart audits demonstrated that injuries were missed in 24% of patients. Clinical information discrepancies occurred in 48% of patients. Patients with these discrepancies were more likely to have unknown medical histories (p<0.001) requiring information rescue (p<0.005). Close to one in three patients with information rescue had a change in clinical management (p<0.01). Participants identified challenges according to their disciplines, with some overlap. Physicians, in contrast to nurses, were perceived as less aware of interdisciplinary stress and their role regarding variability in handover. Standardising handover, increasing non-technical physician training and understanding unit cultures were proposed as solutions, with nurses as drivers of a culture of safety. CONCLUSION: Trauma patient information was lost during handover from the ED to the ICU for multiple reasons. An interprofessional approach was proposed to improve handover through cross-unit familiarisation and use of communication tools is proposed. Going beyond traditional geographical and temporal boundaries was deemed important for improving patient safety during the ED to ICU handover. PMID- 26545706 TI - Cost Sharing, Health Care Expenditures, and Utilization: An International Comparison. AB - Health systems implement cost sharing to help reduce health care expenditure and utilization by discouraging the use of unnecessary health care services. We examine cost sharing in 28 countries in the Organisation for Economic Co operation and Development from 1999 through 2009 in the areas of medical care, hospital care, and pharmaceuticals. We investigate associations between cost sharing, health care expenditures, and health care utilization and find no significant association between cost sharing and health care expenditures or utilization in these countries. PMID- 26545707 TI - Locoregional Treatment in Early Stage Breast Cancer: More Evidence and Yet More Questions? PMID- 26545708 TI - What do we do about women athletes with testes? AB - Elite sport and the measures imposed to prevent 'men' from 'cheating' by posing as women in women's events cast interesting light on notions of sex and gender. Some women have testes, organs that produce testosterone, because they are trans women or they have an intersex state. Testosterone is recognised as a performance enhancing substance in at least some circumstances, and therefore, women with testes may possess an advantage when competing in some sport against women without testes, though this has never been subjected to rigorous scientific testing. The International Olympic Committee and the International Association of Athletics Federation have decreed that such individuals can compete only if they undergo medical and surgical treatment, which is likely to mean gonadectomy. This might be considered to impose an unethical demand on the individual concerned and constitute an infringement of bodily autonomy for that individual. It also suggests a binary view of sex/gender that is simplistic and not scientifically accurate. I discuss this approach and consider alternative methods of approaching the problem of women with testes in athletics. PMID- 26545709 TI - Having a child together in lesbian families: combining gestation and genetics. AB - The increasing acceptance of lesbian couples in medically assisted reproduction has led to new, unusual requests. This paper discusses the request for egg transfer from one partner to the other. In the first part, different analogies (egg donation, embryo donation, surrogacy and mitochondrial replacement) are made in order to find out whether one of these can help us determine whether this procedure is acceptable. It is shown that there are major difficulties with all analogies. In the second part, two balances are developed between the medical risks and costs of in vitro fertilisation (IVF) and intrauterine insemination on the one hand and the medical risks of IVF and the psychosocial benefits on the other hand. The final conclusion is that the disadvantages of the procedure can be compensated by the psychosocial advantages and thus can be accepted. PMID- 26545710 TI - Accelerated cardiac remodeling in desmoplakin transgenic mice in response to endurance exercise is associated with perturbed Wnt/beta-catenin signaling. AB - Arrhythmogenic ventricular cardiomyopathy (AVC) is a frequent underlying cause for arrhythmias and sudden cardiac death especially during intense exercise. The mechanisms involved remain largely unknown. The purpose of this study was to investigate how chronic endurance exercise contributes to desmoplakin (DSP) mutation-induced AVC pathogenesis. Transgenic mice with overexpression of desmoplakin, wild-type (Tg-DSP(WT)), or the R2834H mutant (Tg-DSP(R2834H)) along with control nontransgenic (NTg) littermates were kept sedentary or exposed to a daily running regimen for 12 wk. Cardiac function and morphology were analyzed using echocardiography, electrocardiography, histology, immunohistochemistry, RNA, and protein analysis. At baseline, 4-wk-old mice from all groups displayed normal cardiac function. When subjected to exercise, all mice retained normal cardiac function and left ventricular morphology; however, Tg-DSP(R2834H) mutants displayed right ventricular (RV) dilation and wall thinning, unlike NTg and Tg DSP(WT). The Tg-DSP(R2834H) hearts demonstrated focal fat infiltrations in RV and cytoplasmic aggregations consisting of desmoplakin, plakoglobin, and connexin 43. These aggregates coincided with disruption of the intercalated disks, intermediate filaments, and microtubules. Although Tg-DSP(R2834H) mice already displayed high levels of p-GSK3-beta(Ser9) and p-AKT1(Ser473) under sedentary conditions, decrease of nuclear GSK3-beta and AKT1 levels with reduced p-GSK3 beta(Ser9), p-AKT1(Ser473), and p-AKT1(Ser308) and loss of nuclear junctional plakoglobin was apparent after exercise. In contrast, Tg-DSP(WT) showed upregulation of p-AKT1(Ser473), p-AKT1(Ser308), and p-GSK3-beta(Ser9) in response to exercise. Our data suggest that endurance exercise accelerates AVC pathogenesis in Tg-DSP(R2834H) mice and this event is associated with perturbed AKT1 and GSK3-beta signaling. Our study suggests a potential mechanism-based approach to exercise management in patients with AVC. PMID- 26545711 TI - Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats. AB - The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20-50 MUA in 10-MUA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 MUA, DeltaRSNA: WKY 153 +/- 31%, SHR 287 +/- 42%; DeltaMAP: WKY 87 +/- 9 mmHg, SHR 139 +/- 7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension. PMID- 26545712 TI - The Pan-African Rabies Control Network (PARACON): A unified approach to eliminating canine rabies in Africa. AB - Even though Africa has the highest per capita death rate from rabies of any continent, and the disease is almost entirely transmitted by the bites of rabid dogs, there has been no coordinated pan-African approach to controlling canine rabies. In order to attain an inclusive and unified network, the Pan-African Rabies Control Network (PARACON) was established in 2014. By following the 'One Health' concept, which involves close coordination between animal and human health sectors across national, regional and continental levels, PARACON will provide a platform to facilitate and promote coordinated and sustainable control strategies and programmes. Meetings will take place at regular intervals and will be centred on the involvement by key focal persons from the medical and veterinary sectors. The inaugural meeting was held in South Africa in June, 2015 and was focused around interactive discussions and workshops, whilst updating country representatives on the tools available to aid them in developing and implementing sustainable rabies intervention strategies. Experts from various global organizations, institutions and industry participated in the discussions and shared their experience and expertise. The workshops focused on the latest format of the Rabies Blueprint platform (www.rabiesblueprint.com), which in the broadest sense assists with control and elimination campaigns, including educational and advocacy drives, improvement of surveillance and diagnosis and the systematic monitoring of progress. Together with the Stepwise Approach towards Rabies Elimination, the Blueprint is a planning tool to help countries free themselves from canine-transmitted rabies. PMID- 26545713 TI - 30th Anniversary issue of Biosensors and Bioelectronics. PMID- 26545714 TI - Superoxide produced in the matrix of mitochondria enhances methylmercury toxicity in human neuroblastoma cells. AB - The mechanism of intracellular metabolism of methylmercury (MeHg) is not fully known. It has been shown that superoxide (O2(-)), the proximal reactive oxygen species (ROS) generated by mitochondria, is responsible for MeHg demethylation. Here, we investigated the impact of different mitochondrial respiratory inhibitors, namely rotenone and antimycin A, on the O2(-)mediated degradation of MeHg in human neuroblastoma cells SH-K-SN. We also utilized paraquat (PQ) which generates O2(-) in the mitochondrial matrix. We found that the cleavage of the carbon-metal bond in MeHg was highly dependent on the topology of O2(-) production by mitochondria. Both rotenone and PQ, which increase O2(-) in the mitochondrial matrix at a dose-dependent manner, enhanced the conversion of MeHg to inorganic mercury (iHg). Surprisingly, antimycin A, which prompts emission of O2(-) into the intermembrane space, did not have the same effect even though antimycin A induced a dose dependent increase in O2(-) emission. Rotenone and PQ also enhanced the toxicity of sub-toxic doses (0.1 MUM) MeHg which correlated with the accumulation of iHg in mitochondria and depletion of mitochondrial protein thiols. Taken together, our results demonstrate that MeHg degradation is mediated by mitochondrial O2(-), specifically within the matrix of mitochondria when O2(-) is in adequate supply. Our results also show that O2(-) amplifies MeHg toxicity specifically through its conversion to iHg and subsequent interaction with protein cysteine thiols (R-SH). The implications of our findings in mercury neurotoxicity are discussed herein. PMID- 26545715 TI - Finding positives after disaster: Insights from nurses following the 2010-2011 Canterbury, NZ earthquake sequence. AB - BACKGROUND: This paper identifies positive aspects of nurse experiences during the Canterbury 2010-2011 earthquake sequence and subsequent recovery process. METHODS: Qualitative semi-structured interviews were undertaken with 11 nurses from the Christchurch area to explore the challenges faced by the nurses during and following the earthquakes. The interviews took place three years after the start of the earthquake experience to enable exploration of the longer term recovery process. The interview transcripts were analysed and coded using a grounded theory approach. RESULTS: The data analysis identified that despite the many challenges faced by the nurses during and following the earthquakes they were able to identify positives from their experience. A number of themes were identified that are related to posttraumatic growth, including; improvement in relationships with others, change in perspective/values, changed views of self and acknowledgement of the value of the experience. CONCLUSIONS: The research indicates that nurses were able to identify positive aspects of their experiences of the earthquakes and recovery process, suggesting that both positive and negative impacts on wellbeing can co-exist. These insights have value for employers designing support processes following disasters as focusing on positive elements could enhance nurse wellbeing during stressful times. PMID- 26545716 TI - Detecting Burrowing Owl Bloodmeals in Pulex irritans (Siphonaptera: Pulicidae). AB - Pulex irritans L. is a cosmopolitan flea species that infests a wide variety of hosts. In North America it generally parasitizes large wild mammals, but in the Pacific Northwest an association has emerged between P. irritans and the western burrowing owl (Athene cunicularia hypugaea). While investigators have recognized this association for decades, it has not been clear if P. irritans feeds on burrowing owls, or if the owls serve exclusively as phoretic hosts. Here we describe using a real-time assay that was originally developed to identify bloodmeals in Ugandan cat fleas (Ctenocephalides felis Bouche) to detect burrowing owl DNA in P. irritans collected from burrowing owls in southern Idaho. Of 50 fleas tested, 12 had no detectable vertebrate bloodmeal. The remaining 38 (76%) contained burrowing owl DNA. The assay did not detect vertebrate DNA in unfed fleas exposed to owl or mouse pelts and is therefore unlikely to detect DNA in fleas from vertebrates that have served exclusively as phoretic hosts. We conclude that P. irritans feeds on burrowing owls. We discuss the potential implications of this finding for burrowing owl conservation and enzootic plague dynamics. PMID- 26545717 TI - A Novel Nit Comb Concept Using Ultrasound Actuation: Preclinical Evaluation. AB - Nit combing and removal of head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), eggs is a task made more difficult because "nit combs" vary in efficiency. There is currently no evidence that the binding of the eggshell to the hair can be loosened chemically and few hair treatments improve the slip of the louse eggs along the hair. Ultrasound, applied through the teeth of a nit comb, may facilitate the flow of fluids into the gap between the hair shaft and the tube of fixative holding louse eggs in place to improve lubrication. Ultrasound alone had little effect to initiate sliding, requiring a force of 121.5 +/- 23.8 millinewtons (mN) compared with 125.8 +/- 18.0 mN without ultrasound, but once the egg started to move it made the process easier. In the presence of a conditioner-like creamy lotion, ultrasound reduced the Peak force required to start movement to 24.3 +/- 8.8 mN from 50.4 +/- 13.0 mN without ultrasound. In contrast, some head louse treatments made removal of eggs more difficult, requiring approximately twice the Peak force to initiate movement compared with dry hair in the absence of ultrasound. However, following application of ultrasound, the forces required to initiate movement increased for an essential oil product, remained the same for isopropyl myristate and cyclomethicone, and halved for 4% dimeticone lotion. Fixing the nit comb at an estimated angle of 16.5 degrees to the direction of pull gave an optimum effect to improve the removal process when a suitable lubricant was used. PMID- 26545718 TI - How Important is Vertical Transmission of Dengue Viruses by Mosquitoes (Diptera: Culicidae)? AB - Vertical transmission of dengue viruses by mosquitoes was discovered at the end of the late 1970s and has been suggested to be a means by which these viruses persist. However, it is unclear how widespread it is in nature, and its importance in the epidemiology of this disease is still debated. Here, we review the literature on vertical transmission and discuss its role in dengue's epidemiology and control. We conclude that given the number of studies that failed to find evidence of vertical transmission, as well as mathematical models and its mechanistic basis, it is unlikely that vertical transmission is important for the epidemiological persistence of dengue viruses. A combination of asymptomatic infection in humans and movement of people are likely to be more important determinants of dengue's persistence. We argue, however, that there may be some need for further research into the prevalence of dengue viruses in desiccated, as well as diapausing, eggs and the role of horizontal transmission through larval cannibalism. PMID- 26545719 TI - Case report of bilateral relapsing-remitting sciatic nerve palsy during two pregnancies. AB - BACKGROUND: Unlike puerperal peripheral nerve lesions, mononeuropathy during pregnancy is rarely encountered. We report a case of bilateral relapsing remitting sciatic nerve palsy during two pregnancies. An extensive literature search in PubMed brought no similar cases. CASE PRESENTATION: A healthy young woman presented with initially unilateral sciatic nerve palsy, which manifested and worsened during the early phases of two successive pregnancies. Electrophysiology revealed axonal lesion of the sciatic nerve with predominant affection of the peroneal part. Extensive laboratory examination including cerebrospinal fluid examination was unremarkable. MR imaging was compatible with bilateral intraneural perineurioma. Recurrent occurrence during two pregnancies and an anamnestic relationship between intermediate worsening of the paresis and the menstrual cycle suggested hormone-dependency of the tumor. However, response to repeated intravenous immunoglobuline (IVIG) therapy during pregnancy and shortly after childbirth resulted in partial reversion of foot drop. This was also indicative of an immunoneuropathy. Nerve biopsy was not performed because of clinical improvement. The precise underlying neuropathological mechanism remained unclear. CONCLUSION: To increase knowledge and awareness of this rare entity, potential etiologies of mononeuropathies during pregnancy are discussed in the context of this case report. In the rare occasion of peripheral nerve mononeuropathy during pregnancy, in which therapeutic opportunities are limited, IVIG therapy may be an option when the etiology cannot clearly be determined after thorough medical investigation. PMID- 26545720 TI - Deformable image registration by combining uncertainty estimates from supervoxel belief propagation. AB - Discrete optimisation strategies have a number of advantages over their continuous counterparts for deformable registration of medical images. For example: it is not necessary to compute derivatives of the similarity term; dense sampling of the search space reduces the risk of becoming trapped in local optima; and (in principle) an optimum can be found without resorting to iterative coarse-to-fine warping strategies. However, the large complexity of high dimensional medical data renders a direct voxel-wise estimation of deformation vectors impractical. For this reason, previous work on medical image registration using graphical models has largely relied on using a parameterised deformation model and on the use of iterative coarse-to-fine optimisation schemes. In this paper, we propose an approach that enables accurate voxel-wise deformable registration of high-resolution 3D images without the need for intermediate image warping or a multi-resolution scheme. This is achieved by representing the image domain as multiple comprehensive supervoxel layers and making use of the full marginal distribution of all probable displacement vectors after inferring regularity of the deformations using belief propagation. The optimisation acts on the coarse scale representation of supervoxels, which provides sufficient spatial context and is robust to noise in low contrast areas. Minimum spanning trees, which connect neighbouring supervoxels, are employed to model pair-wise deformation dependencies. The optimal displacement for each voxel is calculated by considering the probabilities for all displacements over all overlapping supervoxel graphs and subsequently seeking the mode of this distribution. We demonstrate the applicability of this concept for two challenging applications: first, for intra-patient motion estimation in lung CT scans; and second, for atlas-based segmentation propagation of MRI brain scans. For lung registration, the voxel-wise mode of displacements is found using the mean-shift algorithm, which enables us to determine continuous valued sub-voxel motion vectors. Finding the mode of brain segmentation labels is performed using a voxel-wise majority voting weighted by the displacement uncertainty estimates. Our experimental results show significant improvements in registration accuracy when using the additional information provided by the registration uncertainty estimates. The multi-layer approach enables fusion of multiple complementary proposals, extending the popular fusion approaches from multi-image registration to probabilistic one-to-one image registration. PMID- 26545721 TI - Awareness and low uptake of post exposure prophylaxis for HIV among clinical medical students in a high endemicity setting. AB - BACKGROUND: Adequate knowledge and practices on post exposure prophylaxis (PEP) for HIV among health care providers are crucial for HIV prevention. However there is limited data on PEP knowledge and practice from developing countries where the burden of HIV infection continues to increase. We assessed the knowledge of clinical medical students on PEP, their practices in response to occupational exposure to HIV, as well as the determinants of good knowledge on PEP. METHODS: A cross-sectional study was conducted in November 2014 involving 154 consecutively recruited clinical medical students (4(th)-6(th) year undergraduates). Data were acquired using a structured questionnaire. Knowledge on PEP was assessed using a questionnaire comprising 25 questions and categorized as: good (20 or more correct answers), moderate (13-19 correct answers) and poor (12 or fewer correct answers). RESULTS: For the 154 students included (57.8 % being male), the mean age was 23.2 +/- 2.4 years, and 89 % had heard about PEP for HIV. The majority of students had moderate (61.7 %) and poor (32.5 %) knowledge on PEP. Overall knowledge score increased with increasing level of studies (p < 0.05). Only 10 (6.5 %) had had previous training on PEP, most of whom were senior level students (p = 0.01). Fifty-four students (35.1 %) knew the appropriate duration of PEP and this awareness increased with level of studies (p = 0.001). Of the 81 (52.6 %) who reported occupational exposure to HIV in the past, only 4 (4.9 %) received PEP. CONCLUSIONS: Overall, knowledge on PEP among clinical medical students in this setting was non-optimal with very low uptake PEP. Intensification of HIV curricula to involve PEP as well as continuous medical education programs and workshops are potential avenues to improve awareness in this vulnerable population. PMID- 26545723 TI - [History of glaucoma surgery (II): From goniotomy to the first non-penetrating surgery]. PMID- 26545722 TI - Primary myeloma interaction and growth in coculture with healthy donor hematopoietic bone marrow. AB - BACKGROUND: Human primary myeloma (MM) cells do not survive in culture; current in vitro and in vivo systems for growing these cells are limited to coculture with a specific bone marrow (BM) cell type or growth in an immunodeficient animal model. The purpose of the study is to establish an interactive healthy donor whole BM based culture system capable of maintaining prolonged survival of primary MM cells. This normal BM (NBM) coculture system is different from using autologous BM that is already affected by the disease. METHODS: Whole BM from healthy donors was cultured in medium supplemented with BM serum from MM patients for 7 days, followed by 7 days of coculture with CD138-selected primary MM cells or MM cell lines. MM cells in the coculture were quantified using flow cytometry or bioluminescence of luciferase-expressing MM cells. T-cell cytokine array and proteomics were performed to identify secreted factors. RESULTS: NBM is composed of adherent and nonadherent compartments containing typical hematopoietic and mesenchymal cells. MM cells, or a subset of MM cells, from all examined cases survived and grew in this system, regardless of the MM cells' molecular risk or subtype, and growth was comparable to coculture with individual stromal cell types. Adherent and nonadherent compartments supported MM growth, and this support required patient serum for optimal growth. Increased levels of MM growth factors IL-6 and IL-10 along with MM clinical markers B2M and LDHA were detected in supernatants from the NBM coculture than from the BM cultured alone. Levels of extracellular matrix factors (e.g., MMP1, HMCN1, COL3A1, ACAN) and immunomodulatory factors (e.g., IFI16, LILRB4, PTPN6, AZGP1) were changed in the coculture system. The NBM system protected MM cells from dexamethasone but not bortezomib, and effects of lenalidomide varied. CONCLUSIONS: The NBM system demonstrates the ability of primary MM plasma cells to interact with and to survive in coculture with healthy adult BM. This model is suitable for studying MM-microenvironment interactions, particularly at the early stage of engagement in new BM niches, and for characterizing MM cell subpopulations capable of long term survival through secretion of extracellular matrix and immune-related factors. PMID- 26545725 TI - A Perplexing "Target Sign". PMID- 26545724 TI - Early Biomarkers of Subclinical Atherosclerosis in Obese Adolescent Girls with Polycystic Ovary Syndrome. AB - OBJECTIVES: Because in obese youth, pulse wave velocity (PWV), an early cardiovascular disease marker, is elevated, we tested if obese girls with polycystic ovary syndrome (OB-PCOS) have higher PWV and carotid intima-media thickness (cIMT) compared with obese girls without PCOS (OB-non-PCOS) and normal weight girls without PCOS (NW-non-PCOS) and whether PWV and cIMT correlate with inflammatory and circulating endothelial function biomarkers. STUDY DESIGN: Cross sectional study of PWV and cIMT in 91 OB-PCOS, 30 obese controls (OB-non-PCOS), and 19 normal-weight controls (NW-non-PCOS). Body composition, blood pressure, fasting glucose, insulin, lipid concentrations, and endothelial function biomarkers were measured. OB-non-PCOS and OB-PCOS underwent 2-hour oral glucose tolerance testing. RESULTS: PWV was higher in OB-PCOS (664 +/- 24 cm/s) and OB non-PCOS (624 +/- 37 cm/s) compared with NW-non-PCOS (468 +/- 13 cm/s, P < .001), with no differences in cIMT. Systolic blood pressure, low-density lipoprotein, and non-high-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol and indices of insulin sensitivity were lower in OB-PCOS and OB-non-PCOS compared with NW-non-PCOS. Vascular cell adhesion molecule-1 and high-sensitivity C-reactive protein were higher in OB-PCOS compared with NW-non PCOS. PWV correlated with adiposity (rs = .46), insulin sensitivity index (homeostatic model assessment-insulin resistance rs = .31), systolic blood pressure (rs = .24; P <= .003 for all), and free testosterone (rs = .24; P = .03). In multiple regression analysis with PWV as the dependent variable and age, race, body mass index, PCOS, and dysglycemia as independent variables, only body mass index was an independent contributor to the model (r(2) = 0.068, P = .003). CONCLUSIONS: In adolescent girls, obesity and not PCOS appears to be associated with heightened cardiovascular disease risk. Increased PWV, vascular cell adhesion molecule-1, and high-sensitivity C-reactive protein may be the earliest subclinical atherosclerosis biomarkers in OB-PCOS. PMID- 26545727 TI - 2010 American College of Rheumatology Adult Fibromyalgia Criteria for Use in an Adolescent Female Population with Juvenile Fibromyalgia. AB - OBJECTIVES: To evaluate the utility of the 2010 American College of Rheumatology (ACR) adult fibromyalgia criteria for use in adolescents with juvenile fibromyalgia (JFM). STUDY DESIGN: Participants included 47 adolescent girls diagnosed with JFM (mean age = 15.3 years) and 48 age- and sex-matched adolescents (mean age = 15.0 years) with localized chronic pain (eg, headaches or abdominal pain). A trained examiner administered the Widespread Pain Index and Symptom Severity measures and also completed a manual tender point exam. Clinicians completed a form indicating the presence of active JFM per Yunus and Masi (1985) criteria, the only available and most commonly used measure for JFM. Criterion validity analysis was performed as well as t tests comparing symptoms between JFM and controls. RESULTS: With the Yunus and Masi criteria used as the gold standard, the 2010 ACR fibromyalgia criteria showed a sensitivity of 89.4% and specificity of 87.5%. CONCLUSION: The 2010 ACR measure appears to be a valuable tool for the identification of JFM. However, a slight modification to the 2010 ACR measure and inclusion of a clinical exam is recommended. PMID- 26545728 TI - Outbreaks of Invasive Kingella kingae Infections in Closed Communities. AB - OBJECTIVES: To describe the results of the epidemiologic investigation of outbreaks of invasive Kingella kingae infections among attendees at daycare facilities located in 4 closed communities in Israel. STUDY DESIGN: The preschool aged population of communities with clusters of Kingella cases had oropharyngeal cultures performed. K kingae isolates from infected patients and healthy contacts were genotyped by pulsed field gel electrophoresis to determine the spread of outbreak strains. RESULTS: The affected closed communities (3 military bases and 1 "kibbutz" commune) were characterized by tight social and family networks and intensive mingling. The outbreaks affected 9 of 51 attendees (attack rate: 17.6%) age 8-19 months (median: 12 months), within a 21-day period. Cases included skeletal system infections (n = 8) and bacteremia (n = 1); K kingae isolates were confirmed by the use of blood culture vials and selective media. Clinical presentation was mild and acute-phase reactants were usually normal or only moderately elevated. Thirty out of 55 (54.5%) asymptomatic children carried the outbreak strains. Analysis of the 3 clusters in which the entire preschool-aged population was cultured revealed that 31 of 71 (43.7%) children younger than 24 months of age were colonized with K kingae organisms compared with 8 of 105 (7.6%) older children (P < .001). CONCLUSIONS: Clusters of invasive K kingae infections characterized by sudden onset, high attack rate, and wide dissemination of the outbreak strain can occur in daycare facilities and closed communities. Because the mild clinical presentation of invasive K kingae infections and the fastidious nature of the organism, a high index of suspicion and use of sensitive detection methods are recommended. PMID- 26545726 TI - Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis. AB - OBJECTIVE: To evaluate the clinical safety of antenatal and postnatal N acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. STUDY DESIGN: Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. RESULTS: Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. CONCLUSIONS: In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00724594. PMID- 26545729 TI - Erratum to: Association of KCNB1 polymorphisms with lipid metabolisms and insulin resistance: a case-control design of population-based cross-sectional study in Chinese Han population. PMID- 26545730 TI - Serum caspase-3 levels and mortality are associated in patients with severe traumatic brain injury. AB - BACKGROUND: Different apoptosis pathways activate caspase-3. In a study involving 27 patients with traumatic brain injury (TBI), higher caspase-3 levels were found in contusion brain tissue resected from non-survivors than from survivors. The objective of this study was to determine whether there is an association in TBI patients between serum caspase-3 levels (thus using an easier, quicker, less expensive and less invasive procedure) and mortality, in a larger series of patients. METHODS: We carried out a prospective, observational and multicenter study in six Spanish Hospital Intensive Care Units including 112 patients with severe TBI. All had Glasgow Coma Scale (GCS) scores lower than 9. Patients with an Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Blood samples were collected on day 1 of TBI to measure serum caspas-3 levels. The endpoint was 30-day mortality. RESULTS: We found that non-surviving patients (n = 31) showed higher (p = 0.003) serum caspase-3 levels compared to survivors (n = 81). Kaplan-Meier survival analysis showed a higher risk of death in TBI patients with serum caspase-3 levels >0.20 ng/mL than in patients with lower concentrations (Hazard Ratio = 3.15; 95% CI = 1.40 to 7.08; P < 0.001). Multiple logistic regression analysis showed that serum caspase-3 levels > 0.20 ng/mL were associated with mortality at 30 days in TBI patients controlling for Marshall CT classification, age and GCS (Odds ratio = 7.99; 95% CI = 2.116 to 36.744; P = 0.001). CONCLUSIONS: The association between serum caspase-3 levels and mortality in TBI patients was the major novel finding of our study. PMID- 26545731 TI - The Effect of Entonox, Play Therapy and a Combination on Pain Relief in Children: A Randomized Controlled Trial. AB - Pediatric pain is often undertreated/neglected due to time constraints, difficulties in timing of oral analgesics, fear of side effects of opioids and anxiolytics, and apprehension of additional pain in the use of local anesthetic injections. In this study, the researcher was prompted to choose rapidly acting interventions that were low dose and allowed the child to stay alert, suitable for a quick discharge. The purpose of this study was to evaluate the effects of Entonox, play therapy, and a combination to relieve procedural pain in children aged 4-15 years. The study was designed as a randomized controlled trial; the subjects were divided into four groups using a sequential allocation plan from 123 total subjects. Group A received Entonox, Group B received play therapy, Group C received both Entonox and play therapy, and Group D received existing standard interventions. The study was vetted by the departmental study review committee. The pain level was assessed using FLACC scale for children aged 4-9 years and the Wong Bakers Faces Pain Scale for children aged 10-15 years; scores ranged from 0 to 10. All the data were analyzed using SPSS 16.0 with descriptive statistics and, inferential statistics. The mean pain scores were as follows: Entonox group, 2.87; Play therapy group, 4; combination group, 3; and control group, 5.87. When statistical testing was applied, a significant reduction in the pain score in all the three experimental groups when compared to the control group was found (p = .002), but not in the pain score among the three experimental groups (p = .350). The findings of this study indicated that all three interventions were effective in lowering pain scores when compared to the control group. Play therapy is as potent as Entonox in relieving procedural pain, though there was no additive effect on pain relief when play therapy and Entonox were combined. A protocol for age-related choice between play therapy and Entonox administration was introduced as a standing order in the Pediatric Surgery department for acute procedural pain relief. PMID- 26545733 TI - Distortion correction of EPI data using multimodal nonrigid registration with an anisotropic regularization. AB - In this paper, a novel strategy for correcting both geometric and image intensity distortions of echo-planar imaging (EPI) MRI data is presented. To deal with small local distortions caused by rapid changes of the magnetic field, an improved multimodal registration framework using normalized mutual information (NMI) in combination with a multi-scale technique is presented to estimate a dense displacement field. To ensure the robustness of this high dimensional ill posed inverse problem, a novel anisotropic regularization functional is used. In order to quantify geometric distortions, a new quality measure, called standardized contour distance (SCD), is introduced. It uses the outer structure shape (OSS) information as basis for the evaluation. The new registration method was evaluated with one monomodal phantom data set and two multimodal human brain data sets (BrainSuite trainings data, SPM Subject data). By comparing with recent and efficient techniques of the state of the art, in the monomodal case, the new approach achieves results comparable to the sum of squared differences as data term. In the multimodal cases, our new registration strategy improves the mean of the SCD from 0.96+/-0.11 to 0.60+/-0.13 in case of the SPM Subject data and from 0.92+/-0.07 to 0.78+/-0.11 in case of the BrainSuite trainings data. PMID- 26545732 TI - Characteristics of Patients with Lower Extremity Trauma with Improved and Not Improved Pain During Hospitalization: A Pilot Study. AB - Up to 62% of patients report chronic pain at the injury site 6-12 months after blunt trauma, with pain from lower extremity fractures exceeding that from other sites. High pain intensity at time of injury is a risk factor for chronic pain, but it is not clear what patient characteristics influence the pain intensity level during the immediate hospitalization following injury. The purpose of this pilot study was to determine the feasibility of collecting pain scores from medical records to calculate pain trajectories and to determine whether it is possible to examine patient characteristics by classifying them into those whose pain improved and those whose pain did not improve. This descriptive study retrospectively reviewed medical records of 18 randomly chosen patients admitted to an academic trauma center. Patient characteristics and pain scores were collected form electronic and handwritten medical records. The pain trajectories calculated from routinely collected pain scores during the inpatient stay showed that for 44% of patients the pain improved during the hospitalization, for 39% the pain remained the same, and for 17% the pain worsened. The variables age, smoking, weight, abbreviated injury scores, length of hospital stay, mean pain score, and opioid equianalgesic dose differed based on pain trajectory. While patient characteristics differed based on pain trajectory, any significant effects seen from individual tests should be considered tentative, given the number of analyses conducted on this data set. However, feasibility and significance of conducting a larger study has been established. PMID- 26545734 TI - Actions following adverse drug events - how do these influence uptake and utilisation of newer and/or similar medications? AB - BACKGROUND: Over the last decade, actions following some adverse drug events received major publicity. This study investigated changes in usage patterns of medications in Australia following two examples - rofecoxib market withdrawal (2004) and warnings about jaw necrosis following bisphosphonates (2007). METHODS: Dispensing data for COX-2 inhibitors (2000-2008) and anti-osteoporosis medications (2003-2012) were obtained from the Australian Pharmaceutical Benefits Scheme database. For bisphosphonates, data on Australian marketing expenditures were purchased from Cegedim(R). RESULTS: For COX-2 inhibitors, celecoxib dispensing halved after rofecoxib withdrawal, but meloxicam dispensing increased by 60 %. When lumiracoxib was introduced (2006) there was uptake of prescribing at a faster rate than meloxicam in 2002, its first year of use. For bisphosphonates, alendronate had highest use at the time of the warnings (8.3 DDD/1000/day), dropping to 4.9 DDD/1000/day by 2012. In contrast, risedronate use rose 2007-2012 from 4.1 to 4.9 DDD/1000/day. There was 49 % increase in reported annual expenditure on detailing for risedronate from 2007 to 2008 (to AUD$7.3 million) and only 29 % increase for alendronate (to AUD$3.1 million). CONCLUSIONS: The rapid uptake of prescribing of lumiracoxib and increased use of meloxicam flagged a concern, especially after rofecoxib withdrawal due to safety issues. Bisphosphonates are useful drugs, however the dramatic rise in expenditure on detailing, followed by a rise in utilisation of risedronate could suggest that adverse publicity triggered a marketing response. These examples highlight the importance of tracking utilisation of medication classes in real time, using different data as needed, to ensure that due caution is exercised (and quick intervention provided if needed) for medications in the same class. PMID- 26545735 TI - The relationship between epicardial fat tissue thickness and visceral adipose tissue in lean patients with polycystic ovary syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is related to metabolic syndrome, insulin resistance, and cardiovascular metabolic syndromes. This is particularly true for individuals with central and abdominal obesity because visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) produce a large number of proinflammatory and proatherogenic cytokines. The present study aimed to determine whether there are changes in VAAT and EAT levels which were considered as indirect predictors for subclinical atherosclerosis in lean patients with PCOS. METHODS: The clinical and demographic characteristics of 35 patients with PCOS and 38 healthy control subjects were recorded for the present study. Additionally, the serum levels of various biochemical parameters were measured and EAT levels were assessed using 2D-transthoracic echocardiography. RESULTS: There were no significant differences in mean age (p = 0.056) or mean body mass index (BMI) (p = 0.446) between the patient and control groups. However, the body fat percentage, waist-to-hip ratio, amount of abdominal subcutaneous adipose tissue, and VAAT thickness were higher in the PCOS patient group than in the control group. The amounts of EAT in the patient and control groups were similar (p = 0.384). EAT was correlated with BMI, fat mass, waist circumference, and hip circumference but not with any biochemical metabolic parameters including the homeostasis model assessment of insulin resistance index or the levels of triglycerides, low-density lipoprotein cholesterol, and high density lipoprotein (HDL) cholesterol. However, there was a small positive correlation between the amounts of VAAT and EAT. VAAT was directly correlated with body fat parameters such as BMI, fat mass, and abdominal subcutaneous adipose thickness and inversely correlated with the HDL cholesterol level. CONCLUSIONS: The present study found that increased abdominal adipose tissue in patients with PCOS was associated with atherosclerosis. Additionally, EAT may aid in the determination of the risk of atherosclerosis in patients with PCOS because it is easily measured. PMID- 26545736 TI - Development and psychometric validation of a novel patient survey to assess perceived quality of substance abuse treatment in South Africa. AB - BACKGROUND: A hybrid performance measurement system that combines patient reported outcome data with administrative data has been developed for South African substance abuse treatment services. This paper describes the development and psychometric validation of one component of this system, the South African Addiction Treatment Services Assessment (SAATSA). METHODS: First, a national steering committee identified five domains and corresponding indicators on which treatment quality should be assessed. A decision was made to develop a patient survey to assess several of these indicators. A stakeholder work group sourced survey items and generated additional items where appropriate. The feasibility and face validity of these items were examined during cognitive response testing with 16 patients. This led to the elimination of several items. Next, we conducted an initial psychometric validation of the SAATSA with 364 patients from residential and outpatient services. Exploratory (EFA) and confirmatory factor analyses (CFA) were conducted to assess the latent structure of the SAATSA. Findings highlighted areas where the SAATSA required revision. Following revision, we conducted another psychometric validation with an additional sample of 285 patients. We used EFA and CFA to assess construct validity and we assessed reliability using Cronbach's measure of internal consistency. RESULTS: The final version of the SAATSA comprised 31 items (rated on a four-point response scale) that correspond to six scales. Four of these scales are patient-reported outcome measures (substance use, quality of life, social connectedness and HIV risk outcomes) that together assess the perceived effectiveness of treatment. The remaining two scales assess patients' perceptions of access to and quality of care. The models for the final revised scales had good fit and the internal reliability of these scales was good to excellent, with Cronbach's alpha ranging from 0.72 to 0.89. CONCLUSION: A lack of adequate measurement tools hampers efforts to improve the quality of substance abuse treatment. Our preliminary evidence suggests that the SAATSA, a novel patient survey that assesses patients' perceptions of the outcomes and quality of substance abuse treatment, is a psychometrically robust tool that can help fill this void. PMID- 26545737 TI - Comparison of Kompetitive Allele Specific PCR (KASP) and genotyping by sequencing (GBS) for quality control analysis in maize. AB - BACKGROUND: Quality control (QC) analysis is an important component in maize breeding and seed systems. Genotyping by next-generation sequencing (GBS) is an emerging method of SNP genotyping, which is being increasingly adopted for discovery applications, but its suitability for QC analysis has not been explored. The objectives of our study were 1) to evaluate the level of genetic purity and identity among two to nine seed sources of 16 inbred lines using 191 Kompetitive Allele Specific PCR (KASP) and 257,268 GBS markers, and 2) compare the correlation between the KASP-based low and the GBS-based high marker density on QC analysis. RESULTS: Genetic purity within each seed source varied from 49 to 100% for KASP and from 74 to 100% for GBS. All except one of the inbred lines obtained from CIMMYT showed 98 to 100% homogeneity irrespective of the marker type. On the contrary, only 16 and 21% of the samples obtained from EIAR and partners showed >=95% purity for KASP and GBS, respectively. The genetic distance among multiple sources of the same line designation varied from 0.000 to 0.295 for KASP and from 0.004 to 0.230 for GBS. Five lines from CIMMYT showed <= 0.05 distance among multiple sources of the same line designation; the remaining eleven inbred lines, including two from CIMMYT and nine from Ethiopia showed higher than expected genetic distances for two or more seed sources. The correlation between the 191 KASP and 257,268 GBS markers was 0.88 for purity and 0.93 for identity. A reduction in the number of GBS markers to 1,343 decreased the correlation coefficient only by 0.03. CONCLUSIONS: Our results clearly showed high discrepancy both in genetic purity and identity by the origin of the seed sources (institutions) irrespective of the type of genotyping platform and number of markers used for analyses. Although there were some numerical differences between KASP and GBS, the overall conclusions reached from both methods was basically similar, which clearly suggests that smaller subset of preselected and high quality markers are sufficient for QC analysis that can easily be done using low marker density genotyping platforms, such as KASP. Results from this study would be highly relevant for plant breeders and seed system specialists. PMID- 26545738 TI - Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential. AB - Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative breast cancer results in poor survival. An area of increasing interest is metabolic reprogramming, whereby drug-induced alterations in the metabolic landscape of a tumour slow tumour growth and/or increase sensitivity to existing therapeutics. Nuclear receptors are transcription factors central to the expression of metabolic and transport proteins, and thus represent potential targets for metabolic reprogramming. We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA MB-231 and MDA-MB-468 (triple negative). Furthermore, we show that the mechanism of cell death is predominantly through the intrinsic apoptotic pathway. Finally, we demonstrate that FXR agonists do not stimulate migration in breast cancer cell lines, an important potential adverse effect. Together, our data support the continued examination of FXR agonists as a novel class of therapeutics for the treatment of breast cancer. PMID- 26545739 TI - Livers provide a reliable matrix for real-time PCR confirmation of avian botulism. AB - Diagnosis of avian botulism is based on clinical symptoms, which are indicative but not specific. Laboratory investigations are therefore required to confirm clinical suspicions and establish a definitive diagnosis. Real-time PCR methods have recently been developed for the detection of Clostridium botulinum group III producing type C, D, C/D or D/C toxins. However, no study has been conducted to determine which types of matrices should be analyzed for laboratory confirmation using this approach. This study reports on the comparison of different matrices (pooled intestinal contents, livers, spleens and cloacal swabs) for PCR detection of C. botulinum. Between 2013 and 2015, 63 avian botulism suspicions were tested and 37 were confirmed as botulism. Analysis of livers using real-time PCR after enrichment led to the confirmation of 97% of the botulism outbreaks. Using the same method, spleens led to the confirmation of 90% of botulism outbreaks, cloacal swabs of 93% and pooled intestinal contents of 46%. Liver appears to be the most reliable type of matrix for laboratory confirmation using real-time PCR analysis. PMID- 26545741 TI - 3D Printing and Biofabrication for Load Bearing Tissue Engineering. AB - Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering. PMID- 26545740 TI - Complete genome sequences and analysis of the Fusobacterium nucleatum subspecies animalis 7-1 bacteriophage phiFunu1 and phiFunu2. AB - Fusobacterium nucleatum is a strictly anaerobic, Gram negative bacterial species that has been associated with dental infections, pre-term labor, appendicitis, inflammatory bowel disease, and, more recently, colorectal cancer. The species is unusual in its phenotypic and genotypic heterogeneity, with some strains demonstrating a more virulent phenotype than others; however, as yet the genetic basis for these differences is not understood. Bacteriophage are known to contribute to the virulence phenotype of several bacterial species. In this work, we set out to characterize the bacteriophage associated with F. nucleatum subsp. animalis strain 7-1, a highly invasive isolate from the human gastrointestinal tract. As well, we used computational approaches to predict and compare bacteriophage signatures across available sequenced F. nucleatum genomes. PMID- 26545742 TI - Microfabrication of Cell-Laden Hydrogels for Engineering Mineralized and Load Bearing Tissues. AB - Microengineering technologies and advanced biomaterials have extensive applications in the field of regenerative medicine. In this chapter, we review the integration of microfabrication techniques and hydrogel-based biomaterials in the field of dental, bone, and cartilage tissue engineering. We primarily discuss the major features that make hydrogels attractive candidates to mimic extracellular matrix (ECM), and we consider the benefits of three-dimensional (3D) culture systems for tissue engineering applications. We then focus on the fundamental principles of microfabrication techniques including photolithography, soft lithography and bioprinting approaches. Lastly, we summarize recent research on microengineering cell-laden hydrogel constructs for dental, bone and cartilage regeneration, and discuss future applications of microfabrication techniques for load-bearing tissue engineering. PMID- 26545743 TI - Electrospinning of Bioinspired Polymer Scaffolds. AB - Electrospinning is a technique used in the production of polymer nanofibre meshes. The use of biodegradable and biocompatible polymers to produce nanofibres that closely mimic the extracellular matrix (ECM) of different tissues has opened a wide range of possibilities for the application of electrospinning in Tissue Engineering. It is believed that nano-features (such as voids and surface cues) present in nanofibre mesh scaffolds, combined with the chemical composition of the fibres, can stimulate cell attachment, growth and differentiation. Despite the widespread use of electrospun nanofibres in tissue engineering, the present chapter will focus on the advances made in the utilisation of these materials in bone, cartilage and tooth related applications. Several aspects will be taken into consideration, namely the choice of polymers, the surface modification of the nanofibres in order to achieve mineralisation, and also the biological application of such materials. PMID- 26545744 TI - Bone Tissue Engineering Challenges in Oral & Maxillofacial Surgery. AB - Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies. PMID- 26545745 TI - Engineering Pre-vascularized Scaffolds for Bone Regeneration. AB - Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering. PMID- 26545746 TI - Morphogenic Peptides in Regeneration of Load Bearing Tissues. AB - Morphogenic proteins due to their short half-life require high doses of growth factors in regeneration of load bearing tissues which leads to undesirable side effects. These side effects include bone overgrowth, tumor formation and immune reaction. An alternative approach to reduce undesirable side effects of proteins in regenerative medicine is to use morphogenic peptides derived from the active domains of morphogenic proteins or soluble and insoluble components of the extracellular matrix of mineralized load bearing tissues to induce differentiation of progenitor cells, mineralization, maturation and bone formation. In that regard, many peptides with osteogenic activity have been discovered. These include peptides derived from bone morphogenic proteins (BMPs), those based on interaction with integrin and heparin-binding receptors, collagen derived peptides, peptides derived from other soluble ECM proteins such as bone sialoprotein and enamel matrix proteins, and those peptides derived from vasculoinductive and neuro-inductive proteins. Although these peptides show significant osteogenic activity in vitro and increase mineralization and bone formation in animal models, they are not widely used in clinical orthopedic applications as an alternative to morphogenic proteins. This is partly due to the limited availability of data on structure and function of morphogenic peptides in physiological medium, particularly in tissue engineered scaffolds. Due to their amphiphilic nature, peptides spontaneously self-assemble and aggregate into micellar structures in physiological medium. Aggregation alters the sequence of amino acids in morphogenic peptides that interact with cell surface receptors thus affecting osteogenic activity of the peptide. Aggregation and micelle formation can dramatically reduce the active concentration of morphogenic peptides with many-fold increase in peptide concentration in physiological medium. Other factors that affect bioactivity are the non-specific interaction of morphogenic peptides with lipid bilayer of the cell membrane, interaction of the peptide with cell surface receptors that do not specifically induce osteogenesis leading to less-than-optimal osteogenic activity of the peptide, and less-than optimal interaction of the peptide with osteogenic receptors on the cell surface. Covalent attachment or physical interaction with the tissue engineered matrix can also alter the bioactivity of morphogenic peptides and lead to a lower extent of osteogenesis and bone formation. This chapter reviews advances in discovery of morphogenic peptide, their structural characterization, and challenges in using morphogenic peptides in clinical applications as growth factors in tissue engineered devices for regeneration of load bearing tissues. PMID- 26545747 TI - Osseointegration of Plateau Root Form Implants: Unique Healing Pathway Leading to Haversian-Like Long-Term Morphology. AB - Endosteal dental implants have been utilized as anchors for dental and orthopedic rehabilitations for decades with one of the highest treatment success rates in medicine. Such success is due to the phenomenon of osseointegration where after the implant surgical placement, bone healing results into an intimate contact between bone and implant surface. While osseointegration is an established phenomenon, the route which osseointegration occurs around endosteal implants is related to various implant design factors including surgical instrumentation and implant macro, micro, and nanometer scale geometry. In an implant system where void spaces (healing chambers) are present between the implant and bone immediately after placement, its inherent bone healing pathway results in unique opportunities to accelerate the osseointegration phenomenon at the short-term and its maintenance on the long-term through a haversian-like bone morphology and mechanical properties. PMID- 26545749 TI - Multiphasic, Multistructured and Hierarchical Strategies for Cartilage Regeneration. AB - Cartilage tissue is a complex nonlinear, viscoelastic, anisotropic, and multiphasic material with a very low coefficient of friction, which allows to withstand millions of cycles of joint loading over decades of wear. Upon damage, cartilage tissue has a low self-reparative capacity due to the lack of neural connections, vascularization, and a latent pool of stem/chondro-progenitor cells. Therefore, the healing of articular cartilage defects remains a significant clinical challenge, affecting millions of people worldwide. A plethora of biomaterials have been proposed to fabricate devices for cartilage regeneration, assuming a wide range of forms and structures, such as sponges, hydrogels, capsules, fibers, and microparticles. In common, the fabricated devices were designed taking in consideration that to fully achieve the regeneration of functional cartilage it is mandatory a well-orchestrated interplay of biomechanical properties, unique hierarchical structures, extracellular matrix (ECM), and bioactive factors. In fact, the main challenge in cartilage tissue engineering is to design an engineered device able to mimic the highly organized zonal architecture of articular cartilage, specifically its spatiomechanical properties and ECM composition, while inducing chondrogenesis, either by the proliferation of chondrocytes or by stimulating the chondrogenic differentiation of stem/chondro-progenitor cells. In this chapter we present the recent advances in the development of innovative and complex biomaterials that fulfill the required structural key elements for cartilage regeneration. In particular, multiphasic, multiscale, multilayered, and hierarchical strategies composed by single or multiple biomaterials combined in a well-defined structure will be addressed. Those strategies include biomimetic scaffolds mimicking the structure of articular cartilage or engineered scaffolds as models of research to fully understand the biological mechanisms that influence the regeneration of cartilage tissue. PMID- 26545748 TI - Dentin Matrix Proteins in Bone Tissue Engineering. AB - Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering. PMID- 26545750 TI - Anterior Cruciate Ligament: Structure, Injuries and Regenerative Treatments. AB - Anterior cruciate ligament (ACL) is one of the most vulnerable ligaments of the knee. ACL impairment results in episodic instability, chondral and meniscal injury and early osteoarthritis. The poor self-healing capacity of ACL makes surgical treatment inevitable. Current ACL reconstructions include a substitution of torn ACL via biological grafts such as autograft, allograft. This review provides an insight of ACL structure, orientation and properties followed by comparing the performance of various constructs that have been used for ACL replacement. New approaches, undertaken to induce ACL regeneration and fabricate biomimetic scaffolds, are also discussed. PMID- 26545751 TI - Hard-Soft Tissue Interface Engineering. AB - The musculoskeletal system is comprised of three distinct tissue categories: structural mineralized tissues, actuating muscular soft tissues, and connective tissues. Where connective tissues - ligament, tendon and cartilage - meet with bones, a graded interface in mechanical properties occurs that allows the transmission of load without creating stress concentrations that would cause tissue damage. This interface typically occurs over less than 1 mm and contains a three order of magnitude difference in elastic stiffness, in addition to changes in cell type and growth factor concentrations among others. Like all engineered tissues, the replication of these interfaces requires the production of scaffolds that will provide chemical and mechanical cues, resulting in biologically accurate cellular differentiation. For interface tissues however, the scaffold must provide spatially graded chemical and mechanical cues over sub millimetre length scales. Naturally, this complicates the manufacture of the scaffolds and every stage of their subsequent cell seeding and growth, as each region has different optimal conditions. Given the higher degree of difficulty associated with replicating interface tissues compared to surrounding homogeneous tissues, it is likely that the development of complex musculoskeletal tissue systems will continue to be limited by the engineering of connective tissues interfaces with bone. PMID- 26545752 TI - Cementum and Periodontal Ligament Regeneration. AB - The unique anatomy and composition of the periodontium make periodontal tissue healing and regeneration a complex process. Periodontal regeneration aims to recapitulate the crucial stages of wound healing associated with periodontal development in order to restore lost tissues to their original form and function and for regeneration to occur, healing events must progress in an ordered and programmed sequence both temporally and spatially, replicating key developmental events. A number of procedures have been employed to promote true and predictable regeneration of the periodontium. Principally, the approaches are based on the use of graft materials to compensate for the bone loss incurred as a result of periodontal disease, use of barrier membranes for guided tissue regeneration and use of bioactive molecules. More recently, the concept of tissue engineering has been integrated into research and applications of regenerative dentistry, including periodontics, to aim to manage damaged and lost oral tissues, through reconstruction and regeneration of the periodontium and alleviate the shortcomings of more conventional therapeutic options. The essential components for generating effective cellular based therapeutic strategies include a population of multi-potential progenitor cells, presence of signalling molecules/inductive morphogenic signals and a conductive extracellular matrix scaffold or appropriate delivery system. Mesenchymal stem cells are considered suitable candidates for cell-based tissue engineering strategies owing to their extensive expansion rate and potential to differentiate into cells of multiple organs and systems. Mesenchymal stem cells derived from multiple tissue sources have been investigated in pre-clinical animal studies and clinical settings for the treatment and regeneration of the periodontium. PMID- 26545754 TI - Whole Tooth Regeneration as a Future Dental Treatment. AB - Dental problems caused by dental caries, periodontal disease and tooth injury compromise the oral and general health issues. Current advances for the development of regenerative therapy have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. Tooth regenerative therapy for tooth tissue repair and whole tooth replacement is currently expected a novel therapeutic concept with the full recovery of tooth physiological functions. Dental stem cells and cell-activating cytokines are thought to be candidate approach for tooth tissue regeneration because they have the potential to differentiate into tooth tissues in vitro and in vivo. Whole tooth replacement therapy is considered to be an attractive concept for next generation regenerative therapy as a form of bioengineered organ replacement. For realization of whole tooth regeneration, we have developed a novel three dimensional cell manipulation method designated the "organ germ method". This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial mesenchymal interactions in organogenesis. The bioengineered tooth germ generates a structurally correct tooth in vitro, and erupted successfully with correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was engrafted into an adult jawbone through bone integration. Bioengineered teeth were also able to perform physiological tooth functions such as mastication, periodontal ligament function and response to noxious stimuli. In this review, we describe recent findings and technologies underpinning whole tooth regenerative therapy. PMID- 26545753 TI - Amelogenin in Enamel Tissue Engineering. AB - In this chapter the basic premises, the recent findings and the future challenges in the use of amelogenin for enamel tissue engineering are being discoursed on. Results emerging from the experiments performed to assess the fundamental physicochemical mechanisms of the interaction of amelogenin, the main protein of the enamel matrix, and the growing crystals of apatite, are mentioned, alongside a moderately comprehensive literature review of the subject at hand. The clinical importance of understanding this protein/mineral interaction at the nanoscale are highlighted as well as the potential for tooth enamel to act as an excellent model system for studying some of the essential aspects of biomineralization processes in general. The dominant paradigm stating that amelogenin directs the uniaxial growth of apatite crystals in enamel by slowing down the growth of (hk0) faces on which it adheres is being questioned based on the results demonstrating the ability of amelogenin to promote the nucleation and crystal growth of apatite under constant titration conditions designed to mimic those present in the developing enamel matrix. The role of numerous minor components of the enamel matrix is being highlighted as essential and impossible to compensate for by utilizing its more abundant ingredients only. It is concluded that the three major aspects of amelogenesis outlined hereby--(1) the assembly of amelogenin and other enamel matrix proteins, (2) the proteolytic activity, and (3) crystallization--need to be in precise synergy with each other in order for the grounds for the proper imitation of amelogenesis in the lab to be created. PMID- 26545755 TI - Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis. AB - The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n = 180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini pumps containing either vehicle or nicotine were implanted in the rats 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30 days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine. PMID- 26545756 TI - Occurrence and function of fungal antifungal proteins: a case study of the citrus postharvest pathogen Penicillium digitatum. AB - Antifungal proteins (AFPs) of fungal origin have been described in filamentous fungi. AFPs are small, highly stable, cationic cysteine-rich proteins (CRPs) that are usually secreted in high amounts and show potent antifungal activity against non-self fungi. The role of AFPs in the biology of the producer fungus remains unclear. AFPs have been proposed as promising lead compounds for the development of new antifungals. The analyses of available antifungal CRP sequences from fungal origin and their phylogenetic reconstruction led us to propose a new classification of AFPs in three distinct classes: A, B and C. We initiate for the first time the characterization of an AFP in a fungal pathogen, by analysing the functional role of the unique afpB gene in the citrus fruit pathogen Penicillium digitatum. Null DeltaafpB mutants revealed that this gene is dispensable for vegetative growth and fruit infection. However, strains that artificially express afpB in a constitutive way (afpB (C)) showed a phenotype of restricted growth, distortion of hyphal morphology and strong reduction in virulence to citrus fruits. These characteristics support an antifungal role for AfpB. Surprisingly, we did not detect the AfpB protein in any of the P. digitatum strains and growth conditions that were analysed in this study, regardless of high gene expression. The afpB (C) phenotype is not stable and occasionally reverts to a wild type-like phenotype but molecular changes were not detected with this reversion. The reduced virulence of afpB (C) strains correlated with localized fruit necrosis and altered timing of expression of fruit defence genes. PMID- 26545758 TI - Overcoming hydrolysis of raw corn starch under industrial conditions with Bacillus licheniformis ATCC 9945a alpha-amylase. AB - alpha-Amylase from Bacillus licheniformis ATCC 9945a (BliAmy) was proven to be very efficient in hydrolysis of granular starch below the temperature of gelatinization. By applying two-stage feeding strategy to achieve high-cell density cultivation of Escherichia coli and extracellular production of BliAmy, total of 250.5 U/mL (i.e. 0.7 g/L) of enzyme was obtained. Thermostability of amylase was exploited to simplify purification. The hydrolysis of concentrated raw starch was optimized using response surface methodology. Regardless of raw starch concentration tested (20, 25, 30 %), BliAmy was very effective, achieving the final hydrolysis degree of 91 % for the hydrolysis of 30 % starch suspension after 24 h. The major A-type crystalline structure and amorphous domains of the starch granule were degraded at the same rates, while amylose-lipid complexes were not degraded. BliAmy presents interesting performances on highly concentrated solid starch and could be of value for starch-consuming industries while response surface methodology (RSM) could be efficiently applied for the optimization of the hydrolysis. PMID- 26545757 TI - Evaluation of a recombinant insect-derived amylase performance in simultaneous saccharification and fermentation process with industrial yeasts. AB - Starch is the dominant feedstock consumed for the bioethanol production, accounting for 60 % of its global production. Considering the significant contribution of bioethanol to the global fuel market, any improvement in its major operating technologies is economically very attractive. It was estimated that up to 40 % of the final ethanol unit price is derived from the energy input required for the substrate pre-treatment. Application of raw starch hydrolyzing enzymes (RSHE), combined with operation of the process according to a simultaneous saccharification and fermentation (SSF) strategy, constitutes the most promising solutions to the current technologies limitations. In this study, we expressed the novel RSHE derived from an insect in Saccharomyces cerevisiae strain dedicated for the protein overexpression. Afterwards, the enzyme performance was assessed in SSF process conducted by industrial ethanologenic or thermotolerant yeast species. Comparison of the insect-derived RSHE preparation with commercially available amylolytic RSH preparation was conducted. Our results demonstrate that the recombinant alpha-amylase from rice weevil can be efficiently expressed and secreted with its native signal peptide in S. cerevisiae INVSc-pYES2-Amy1 expression system (accounting for nearly 72 % of the strain's secretome). Application of the recombinant enzyme-based preparation in SSF process secured sufficient amylolytic activity for the yeast cell propagation and ethanol formation from raw starch. (Oligo)saccharide profiles generated by the compared preparations differed with respect to homogeneity of the sugar mixtures. Concomitantly, as demonstrated by a kinetic model developed in this study, the kinetic parameters describing activity of the compared preparations were different. PMID- 26545759 TI - Parallel quorum sensing signaling pathways in Vibrio cholerae. AB - Quorum sensing (QS) is a microbial signaling process for monitoring population density and complexity. Communication among bacterial cells via QS relies on the production, secretion, and detection of small molecules called autoinducers. Many bacteria have evolved their QS systems with different network architectures to incorporate information from multiple signals. In the human pathogen Vibrio cholerae, at least four parallel signaling pathways converge to control the activity of a single regulator to modulate its QS response. By integrating multiple signal inputs, it is believed that Vibrio species can survey intra species, intra-genus, and inter-species populations and program their gene expression accordingly. Our recent studies suggest that this "many-to-one" circuitry is also important for maintaining the integrity of the input-output relationship of the system and minimizes premature commitment to QS due to signal perturbation. Here we discuss the implications of this specific parallel network setup for V. cholerae intercellular communication and how this system arrangement affects our approach to manipulate the QS response of this clinically important pathogen. PMID- 26545761 TI - [Abscopal responses of local radiotherapy combined with systemic immunotherapy in patients with metastatic solid tumors]. PMID- 26545762 TI - [Stereotactic radiotherapy augments the immune response]. PMID- 26545763 TI - Erratum to: Tomotherapy PET-guided dose escalation--A dosimetric feasibility study for patients with malignant pleural mesothelioma. AB - Unfortunately, erroneous author affiliations were published in the article "Tomotherapy PET-guided dose escalation - A dosimetric feasibility study for patients with malignant pleural mesothelioma". The correct list of author affiliations reads as follows: Angelo Maggio 1, Claudia Cutaia 1, Amalia Di Dia 1, Sara Bresciani 1, Anna Miranti 1, Matteo Poli 1, Elena Delmastro 2, Elisabetta Garibaldi 2, Pietro Gabriele 2 and Michele Stasi 1. 1: Medical Physics Department, Candiolo Cancer Institute - FPO, IRCCS, Turin, Italy. 2: Radiotherapy Department, Candiolo Cancer Institute - FPO, IRCCS, Turin, Italy. We apologize for any inconveniences caused. PMID- 26545764 TI - Image-guided intensity-modulated radiotherapy of prostate cancer: Analysis of interfractional errors and acute toxicity. AB - PURPOSE: The aim of the study was to estimate interfractional deviations in patient and prostate position, the impact of the frequency of online verification on the treatment margins, and to assess acute radiation reactions of high-dose external beam image-guided intensity-modulated radiotherapy (IG-IMRT) of localized prostate cancer. PATIENTS AND METHODS: IG-IMRT was performed by daily online verification of implanted fiducial prostate markers using a megavoltage electronic portal imaging device (EPID). A total of 1011 image-guided treatment fractions from 23 consecutive unselected prostate cancer patients were analyzed. The median total dose was 79.2 Gy (range 77.4-81.0 Gy). Acute radiation reactions were assessed weekly during radiotherapy using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. RESULTS: A relevant combined patient set-up and prostate motion population random error of 4-5 mm was observed. Compared to daily IGRT, image guidance every other day required an expansion of the CTV-PTV (clinical target volume-planning target volume) margin of 8.1, 6.6, and 4.1 mm in the longitudinal, vertical, and lateral directions, thereby, increasing the PTV by approximately 30-40 %. No grade 3 or 4 acute radiation reactions were observed with daily IG-IMRT. CONCLUSION: A high dose with surprisingly low acute toxicity can be applied with daily IG-IMRT using implanted fiducial prostate markers. Daily image guidance is clearly superior to image guidance every other fraction concerning adequate target coverage with minimal margins. PMID- 26545765 TI - [Acute toxicity after hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer]. PMID- 26545766 TI - Competitive Deprotonation and Superoxide [O2-*)] Radical-Anion Adduct Formation Reactions of Carboxamides under Negative-Ion Atmospheric-Pressure Helium-Plasma Ionization (HePI) Conditions. AB - Carboxamides bearing an N-H functionality are known to undergo deprotonation under negative-ion-generating mass spectrometric conditions. Herein, we report that N-H bearing carboxamides with acidities lower than that of the hydroperoxyl radical (HO-O(*)) preferentially form superoxide radical-anion (O2(-*)) adducts, rather than deprotonate, when they are exposed to the glow discharge of a helium plasma ionization source. For example, the spectra of N-alkylacetamides show peaks for superoxide radical-anion (O2(-*)) adducts. Conversely, more acidic amides, such as N-alkyltrifluoroacetamides, preferentially undergo deprotonation under similar experimental conditions. Upon collisional activation, the O2(-*) adducts of N-alkylacetamides either lose the neutral amide or the hydroperoxyl radical (HO-O(*)) to generate the superoxide radical-anion (m/z 32) or the deprotonated amide [m/z (M - H)(-)], respectively. For somewhat acidic carboxamides, the association between the two entities is weak. Thus, upon mildest collisional activation, the adduct dissociates to eject the superoxide anion. Superoxide-adduct formation results are useful for structure determination purposes because carboxamides devoid of a N-H functionality undergo neither deprotonation nor adduct formation under HePI conditions. PMID- 26545768 TI - Mind the mind: learning from the cystic fibrosis community. PMID- 26545769 TI - Mycobacterium abscessus in people with cystic fibrosis: considerations for psychosocial care. PMID- 26545767 TI - 213 nm Ultraviolet Photodissociation on Peptide Anions: Radical-Directed Fragmentation Patterns. AB - Characterization of acidic peptides and proteins is greatly hindered due to lack of suitable analytical techniques. Here we present the implementation of 213 nm ultraviolet photodissociation (UVPD) in high-resolution quadrupole-Orbitrap mass spectrometer in negative polarity for peptide anions. Radical-driven backbone fragmentation provides 22 distinctive fragment ion types, achieving the complete sequence coverage for all reported peptides. Hydrogen-deficient radical anion not only promotes the cleavage of Calpha-C bond but also stimulates the breaking of N Calpha and C-N bonds. Radical-directed loss of small molecules and specific side chain of amino acids are detected in these experiments. Radical containing side chain of amino acids (Tyr, Ser, Thr, and Asp) may possibly support the N-Calpha backbone fragmentation. Proline comprising peptides exhibit the unusual fragment ions similar to reported earlier. Interestingly, basic amino acids such as Arg and Lys also stimulated the formation of abundant b and y ions of the related peptide anions. Loss of hydrogen atom from the charge-reduced radical anion and fragment ions are rationalized by time-dependent density functional theory (TDDFT) calculation, locating the potential energy surface (PES) of pipi* and repulsive pisigma* excited states of a model amide system. PMID- 26545770 TI - Get out of the car and on a bike. PMID- 26545760 TI - Extracellular ATP and other nucleotides-ubiquitous triggers of intercellular messenger release. AB - Extracellular nucleotides, and ATP in particular, are cellular signal substances involved in the control of numerous (patho)physiological mechanisms. They provoke nucleotide receptor-mediated mechanisms in select target cells. But nucleotides can considerably expand their range of action. They function as primary messengers in intercellular communication by stimulating the release of other extracellular messenger substances. These in turn activate additional cellular mechanisms through their own receptors. While this applies also to other extracellular messengers, its omnipresence in the vertebrate organism is an outstanding feature of nucleotide signaling. Intercellular messenger substances released by nucleotides include neurotransmitters, hormones, growth factors, a considerable variety of other proteins including enzymes, numerous cytokines, lipid mediators, nitric oxide, and reactive oxygen species. Moreover, nucleotides activate or co-activate growth factor receptors. In the case of hormone release, the initially paracrine or autocrine nucleotide-mediated signal spreads through to the entire organism. The examples highlighted in this commentary suggest that acting as ubiquitous triggers of intercellular messenger release is one of the major functional roles of extracellular nucleotides. While initiation of messenger release by nucleotides has been unraveled in many contexts, it may have been overlooked in others. It can be anticipated that additional nucleotide driven messenger functions will be uncovered with relevance for both understanding physiology and development of therapy. PMID- 26545771 TI - Initial management of spontaneous pneumothorax. PMID- 26545772 TI - Improving the prevention and management of respiratory diseases in China: the crucial role of primary care. PMID- 26545773 TI - Initial management of spontaneous pneumothorax - Authors' reply. PMID- 26545774 TI - Air travel in chronic conditions. PMID- 26545775 TI - Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer. AB - The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment. PMID- 26545776 TI - Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast. AB - Lipid homeostasis in mammalian cells is regulated by sterol regulatory element binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. PMID- 26545777 TI - The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation. AB - The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. PMID- 26545778 TI - Muscle regulatory factors regulate T1R3 taste receptor expression. AB - T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic beta-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity. PMID- 26545779 TI - NOX1 mediates chemoresistance via HIF1alpha/MDR1 pathway in gallbladder cancer. AB - NADPH oxidase 1 (NOX1) plays a key role in tumorigenesis and metastasis through generating reactive oxygen species (ROS), an important intracellular signaling molecule. However, how it is expressed in gallbladder cancer (GBC) tissue sample and whether it associates with GBC chemoresistance have never been investigated. Our study analyzed the relationship between NOX1 expression and cisplatin sensitivity both in vivo and in vitro. We found that reduced NOX1 expression promoted cisplatin efficiency in GBC-SD cells, whereas overexpression of which potentially inhibited the sensitivity of cisplatin in SGC-996 cells. Further study into the mechanism we found that increased NOX1 expression elevated intracellular ROS levels, which then activated HIF-1alpha/MDR1 pathway. These findings established NOX1 a novel accelerant of chemoresistance in GBC, and NOX1 targeted therapeutics might be exploited as a strategy for increasing the efficacy of cisplatin treatment. PMID- 26545780 TI - Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti apoptotic capacities via NFkappaB activation. AB - Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFkappaB activity p65 increased upon mechanical stretch. Inhibition of NFkappaB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells. PMID- 26545781 TI - Del-1 overexpression potentiates lung cancer cell proliferation and invasion. AB - Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial mesenchymal transition (EMT), such as increasing vimentin while decreasing E cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. PMID- 26545782 TI - Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1 carboxylate conjugated GP100(25-33) peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma. AB - It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC) conjugated melanoma tumor antigen GP10025-33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP10025-33 peptide coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naive syngeneic mice was able to transfer anti-tumor effect, suggesting that GP10025-33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-gamma-producing CD8+ T cells upon ex vivo stimulation by GP10025-33 were significantly increased compared to control groups. Tumor antigen, GP10025-23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. PMID- 26545783 TI - Endoplasmic reticulum stress-mediated apoptosis contributes to a skeletal dysplasia resembling platyspondylic lethal skeletal dysplasia, Torrance type, in a novel Col2a1 mutant mouse line. AB - In humans, mutations in the COL2A1 gene encoding the alpha1(II) chain of type II collagen, create many clinical phenotypes collectively termed type II collagenopathies. However, the mechanisms generating this diversity remain to be determined. Here we identified a novel Col2a1 mutant mouse line by screening a large-scale N-ethyl-N-nitrosourea mutant mouse library. This mutant possessed a p.Tyr1391Ser missense mutation in the C-propeptide coding region, and this mutation was located in positions corresponding to the human COL2A1 mutation responsible for platyspondylic lethal skeletal dysplasia, Torrance type (PLSD-T). As expected, p.Tyr1391Ser homozygotes exhibited lethal skeletal dysplasias resembling PLSD-T, including extremely short limbs and severe dysplasia of the spine and pelvis. The secretion of the mutant proteins into the extracellular space was disrupted, accompanied by an abnormally expanded endoplasmic reticulum (ER) and the up-regulation of ER stress-related genes in chondrocytes. Chondrocyte apoptosis was severely induced in the growth plate of the homozygotes. These findings strongly suggest that ER stress-mediated apoptosis caused by the accumulated mutant proteins in ER contributes to skeletal dysplasia in Co12a1 mutant mice and PLSD-T patients. PMID- 26545784 TI - The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2 (S/S) hearts to connexin-43 (Cx43) and Nav1.5 expression and Na(+) current (I Na). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff perfused RyR2 (S/S) hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2 (S/S) than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2 (S/S) compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced I Na in RyR2 (S/S) ventricles. We thus attribute arrhythmogenesis in RyR2 (S/S) ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing I Na, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak I Na of the AP but nonlinear relationships between peak I Na and maximum Na(+) permeability. PMID- 26545789 TI - Lentibacillus amyloliquefaciens sp. nov., a halophilic bacterium isolated from saline sediment sample. AB - A Gram-stain positive, non-motile, non-sporogenous, aerobic, rod-shaped and halophilic bacterium, designated LAM0015(T), was isolated from a saline sediment sample collected from Yantai City in China. The isolate was found to be able to grow at NaCl concentrations of 5-25 % (w/v) (optimum: 7-12 %), 15-45 degrees C (optimum: 35 degrees C) and pH 5.0-9.0 (optimum: 7.0). The major fatty acids were determined to be anteiso-C15:0 and anteiso-C17:0. The predominant respiratory quinone was identified as MK-7. The cell wall peptidoglycan was determined to contain meso-diaminopimelic acid. The polar lipids were found to be diphosphatidyglycerol, phosphatidylglycerol, five phospholipids and one glycolipid. The DNA G+C content was 43.1 mol% as determined by the T m method. Analysis of the 16S rRNA gene sequence indicated that the isolate belongs within the genus Lentibacillus and is closely related to Lentibacillus persicus DSM 22530(T), Lentibacillus salicampi JCM 11462(T) and Lentibacillus jeotgali JCM 15795(T) with 97.3, 96.7 and 96.4 % sequence similarity, respectively. The DNA DNA hybridization value between LAM0015(T) and L. persicus DSM 22530(T) was 51.2 +/- 1.4 %. Based on its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM0015(T) is concluded to represent a novel species of the genus Lentibacillus, for which the name Lentibacillus amyloliquefaciens sp. nov. is proposed. The type strain is LAM0015(T) (=ACCC 06401(T) = JCM 19838(T)). PMID- 26545790 TI - Motoric cognitive risk syndrome and risk of mortality in older adults. AB - INTRODUCTION: Cognitive impairment is associated with increased mortality. We examined the association between motoric cognitive risk (MCR) syndrome, a predementia syndrome characterized by slow gait and cognitive complaints, and survival. METHODS: A total of 11,867 nondemented participants aged >65 years from three established cohort studies in the United States and Europe were screened for MCR. Mortality risk of MCR was assessed with Cox and logistic regression models. RESULTS: At baseline, 836 (7.0%) participants had MCR. Over a median follow-up of 28 months, 1603 participants died (758 in first 2 years). MCR was associated with increased mortality overall (adjusted hazard ratio, 1.69; 95% confidence interval [CI], 1.46-1.96) and 2-year mortality (adjusted odds ratio, 1.89; 95% CI, 1.50-2.38). The association remained after accounting for established mortality risk factors as well as baseline gait speed and memory performance. DISCUSSION: MCR is associated with increased mortality. Older adults should be screened for MCR to identify at-risk individuals for dementia and death. PMID- 26545791 TI - Lexical and age effects on word recognition in noise in normal-hearing children. AB - OBJECTIVES: The purposes of the present study were (1) to examine the lexical and age effects on word recognition of normal-hearing (NH) children in noise, and (2) to compare the word-recognition performance in noise to that in quiet listening conditions. METHODS: Participants were 213 NH children (age ranged between 3 and 6 years old). Eighty-nine and 124 of the participants were tested in noise and quiet listening conditions, respectively. The Standard-Chinese Lexical Neighborhood Test, which contains lists of words in four lexical categories (i.e., dissyllablic easy (DE), dissyllablic hard (DH), monosyllable easy (ME), and monosyllable hard (MH)) was used to evaluate the Mandarin Chinese word recognition in speech spectrum-shaped noise (SSN) with a signal-to-noise ratio (SNR) of 0dB. A two-way repeated-measures analysis of variance was conducted to examine the lexical effects with syllable length and difficulty level as the main factors on word recognition in the quiet and noise listening conditions. The effects of age on word-recognition performance were examined using a regression model. RESULTS: The word-recognition performance in noise was significantly poorer than that in quiet and the individual variations in performance in noise were much greater than those in quiet. Word recognition scores showed that the lexical effects were significant in the SSN. Children scored higher with dissyllabic words than with monosyllabic words; "easy" words scored higher than "hard" words in the noise condition. The scores of the NH children in the SSN (SNR=0dB) for the DE, DH, ME, and MH words were 85.4, 65.9, 71.7, and 46.2% correct, respectively. The word-recognition performance also increased with age in each lexical category for the NH children tested in noise. CONCLUSIONS: Both age and lexical characteristics of words had significant influences on the performance of Mandarin-Chinese word recognition in noise. The lexical effects were more obvious under noise listening conditions than in quiet. The word recognition performance in noise increased with age in NH children of 3-6 years old and had not reached plateau at 6 years of age in the NH children. PMID- 26545792 TI - Corpus alienum on hard palate - An unusual "misdiagnosis" of foreign body: A case report. AB - Corpus alienum or foreign body on hard palate is a rare presentation and often associated with a scare secondary to misdiagnosis. The potential dangers of respiratory obstruction, mucosal tear, nasopharyngeal inflammation and gastro intestinal bleeding make these non-invasive foreign bodies, life threatening. A case report of a three year old girl with a 2.5cm*2cm plastic sticker lodged on hard palate for four months and misdiagnosed as salivary gland tumor has been reported along with a literature review. PMID- 26545793 TI - Auditory neuropathy spectrum disorder (ANSD) and cochlear implantation. AB - We discuss issues related to cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). We describe the varied nature of this disease category including the numerous potential causes of auditory neuropathy. The most prevalent etiology for infants with ANSD is associated with prolonged neonatal intensive care unit (NICU) stay. We discuss the potential contribution of cochlear hypoxia to this etiology. The second part of this review describes in detail our own experience at the Hospital for Sick Children in Toronto, with cochlear implantation of children diagnosed with ANSD. We outline the detection, diagnosis, and referral routes for our patients. We provide an overview of our "standard operation procedures" regarding candidacy, and discuss some of the special considerations that need to be applied to children with ANSD. This includes decisions to implant children with better audiometric thresholds that are standard in non-ANSD patients, concerns about the possibility of spontaneous remission and the appropriate timing of implantation. Finally we review an extensive published literature in outcomes after cochlear implantation (CI) in ANSD. This is not a systematic review but rather an exercise to distill out some important reoccurring themes and the general consensus of opinion to date. Our conclusion is that the hearing loss category ANSD, together with its numerous co morbidities, is far too heterogeneous to make definitive statements about prognosis with CI. PMID- 26545794 TI - Grommets and speech at three and six years in children born with total cleft or cleft palate. AB - OBJECTIVE: Grommets may be considered as the treatment of choice for otitis media with effusion (OME) in children born with a cleft. But the timing and precise indications to use them are not well established. The aim of the study is to compare the results of hearing and speech controls at three and six year-old in children born with total cleft or cleft palate in the presence or not of grommets. METHODS: This retrospective study concerns non syndromic children born between 1994 and 2006 and operated for a unilateral cleft lip palate (UCLP) or a cleft palate (CP) alone, by one surgeon with the same schedule of operations (Malek procedure). We compared the results of clinical observation, tympanometry, audiometry and nasometry at three and six year-old. The Borel-Maisonny classification was used to evaluate the velar insufficiency. None of the children had preventive grommets. The Fisher Exact Test was used for statistical analysis with p<0.05 considered as significant. RESULTS: Seventy-seven patients were analyzed in both groups. Abnormal hearing status was statistically more frequent in children with UCLP compared to children with CP, at three and six years (respectively, 80-64%, p<0.03 and 78-60%, p<0.02), with the use of grommets at six years in 43% of cases in both groups. Improvement of hearing status between three and six year-old was present in 5% of children with UCLP and 9% with CP, without the use of grommets. CONCLUSION: The use of grommets between three and six year-old was not associated to any improvement of hearing status or speech results children with UCLP or with CP, with a low risk of tympanosclerosis. These results favor the use of grommets before the age of three, taking into account the risk of long term tympanosclerosis. PMID- 26545795 TI - Carotid artery pseudoaneurysm: A rare complication following tonsillectomy. AB - Tonsillectomy is one of the most common surgical procedures performed in children. The most frequent complications are dehydration and bleeding. We present the case of a 6 year old child who developed an internal carotid artery pseudoaneurysm following elective tonsillectomy, necessitating urgent coil embolization and stenting. This is the first reported case in the pediatric population of a vascular injury that manifested in a delayed fashion (6 months) after routine tonsillectomy, and is also one of the youngest reported cases. It is imperative for the otolaryngologist to be aware of this rare complication. PMID- 26545796 TI - A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process. AB - Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica. In Drosophila, dual knockdown of the major dietary zinc uptake genes dZIP42C.1 (dZIP1) and dZIP42C.2 (dZIP2) results in a severe sensitivity to zinc-deficient media. However, the symptoms associated with ZIP4 loss can be reversed by zinc supplementation and dZIP42C.1 and 2 knockdown has minimal effect under normal dietary conditions, suggesting that additional pathways for zinc absorption exist in both mammals and flies. This study provides evidence that dZIP89B is an ideal candidate for this role in Drosophila, encoding a low-affinity zinc uptake transporter active in the posterior midgut. Flies lacking dZIP89B, while viable and apparently healthy, show indications of low midgut zinc levels, including reduced metallothionein B expression and compensatory up-regulation of dZIP42C.1 and 2. Furthermore dZIP89B mutants display a dramatic resistance to toxic dietary zinc levels which is abrogated by midgut-specific restoration of dZIP89B activity. We postulate that dZIP89B works in concert with the closely related dZIP42C.1 and 2 to ensure optimal zinc absorption under a range of dietary conditions. PMID- 26545797 TI - Biochemical analyses and molecular modeling explain the functional loss of 17beta hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian patients with 46, XY Disorders of Sex Development. AB - Mutations in the HSD17B3 gene resulting in 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3) deficiency cause 46, XY Disorders of Sex Development (46, XY DSD). Approximately 40 different mutations in HSD17B3 have been reported; only few mutant enzymes have been mechanistically investigated. Here, we report novel compound heterozygous mutations in HSD17B3, composed of the nonsense mutation C206X and the missense mutation G133R, in three Tunisian patients from two non consanguineous families. Mutants C206X and G133R were constructed by site directed mutagenesis and expressed in HEK-293 cells. The truncated C206X enzyme, lacking part of the substrate binding pocket, was moderately expressed and completely lost its enzymatic activity. Wild-type 17beta-HSD3 and mutant G133R showed comparable expression levels and intracellular localization. The conversion of Delta4-androstene-3,17-dione (androstenedione) to testosterone was almost completely abolished for mutant G133R compared with wild-type 17beta-HSD3. To obtain further mechanistic insight, G133 was mutated to alanine, phenylalanine and glutamine. G133Q and G133F were almost completely inactive, whereas G133A displayed about 70% of wild-type activity. Sequence analysis revealed that G133 on 17beta-HSD3 is located in a motif highly conserved in 17beta-HSDs and other short-chain dehydrogenase/reductase (SDR) enzymes. A homology model of 17beta HSD3 predicted that arginine or any other bulky residue at position 133 causes steric hindrance of cofactor NADPH binding, whereas substrate binding seems to be unaffected. The results indicate an essential role of G133 in the arrangement of the cofactor binding pocket, thus explaining the loss-of-function of 17beta-HSD3 mutant G133R in the patients investigated. PMID- 26545798 TI - Discovery of bis-aryl urea derivatives as potent and selective Limk inhibitors: Exploring Limk1 activity and Limk1/ROCK2 selectivity through a combined computational study. AB - Lim kinase (Limk), a proline/serine-rich sequence, can regulate the polymerization of the actin filaments by phosphorylating, and it is found to be highly involved in various human diseases. In this paper, 47 reported Limk1 inhibitors with bis-aryl urea scaffold were used to design potent and selective Limk inhibitors by computational approaches. Firstly, the structure-Limk1 activity relationship models (3D-QSAR) and structure-Limk1/ROCK2 selectivity relationship models (3D-QSSR) were developed and both 3D-QSAR and 3D-QSSR models showed good correlative and predictive abilities. Then, the molecular docking and molecular dynamics (MD) simulations were employed to validate the optimal docking conformation and explore the binding affinities. Finally, five new compounds were designed and all of them exhibited good Limk1 inhibition and Limk1/ROCK2 selectivity after synthesis and biological evaluation, which demonstrated that the obtained information from computational studies were valuable to guide Limk inhibitors' design. PMID- 26545799 TI - Translation elongation factor eEF1A1 is a novel partner of a multifunctional protein Sgt1. AB - Mammalian translation elongation factor eEF1A is involved in ribosomal polypeptide synthesis. Also, the protein fulfills many additional duties in an eukaryotic cell. Here, we identified a novel partner of the eEF1A1 isoform, namely Sgt1, a protein that possesses co-chaperon properties and participates in antiviral defense processes. By applying different methods, we demonstrated the interaction between eEF1A1 and Sgt1 using both purified proteins and cell lysates. We also found that the D2 and D3 domains of eEF1A1 and the TPR domain of Sgt1 are involved in complex formation. Modeling of the Sgt1-eEF1A1 complex suggested both shape and charge complementarities of the eEF1A1-Sgt1 interface stabilized by a number of salt bridges. As long as such interaction mode is typical more for protein-nucleic acid interaction we suggested a possibility that Sgt1 competes with viral RNA for binding to eEF1A and obtained in vitro evidence to this effect. PMID- 26545800 TI - 16S rRNA methyltransferase KsgA contributes to oxidative stress resistance and virulence in Staphylococcus aureus. AB - We previously reported that the rRNA methyltransferases RsmI and RsmH, which are responsible for cytidine dimethylation at position 1402 of 16S rRNA in the decoding center of the ribosome, contribute to Staphylococcus aureus virulence. Here we evaluated other 16S rRNA methyltransferases, including KsgA (RsmA), RsmB/F, RsmC, RsmD, RsmE, and RsmG. Knockout of KsgA, which methylates two adjacent adenosines at positions 1518 and 1519 of 16S rRNA in the intersubunit bridge of the ribosome, attenuated the S. aureus killing ability against silkworms. The ksgA knockout strain was sensitive to oxidative stress and had a lower survival rate in murine macrophages than the parent strain. The ksgA knockout strain exhibited decreased translational fidelity in oxidative stress conditions. Administration of N-acetyl-l-cysteine, a free-radical scavenger, restored the killing ability of the ksgA knockout strain against silkworms. These findings suggest that the methyl-modifications of 16S rRNA by KsgA contribute to maintain ribosome function under oxidative conditions and thus to S. aureus virulence. PMID- 26545801 TI - Postoperative complications associated with extubation strategies following palatoplasty: a single-center retrospective analysis. AB - PURPOSE: Palatoplasty carries a high risk of airway obstruction as a postoperative complication. Since 2007, the protocol in our hospital has been to leave an endotracheal tube in place after surgery while the patient is moved to the pediatric intensive care unit. Extubation is then performed after achievement of hemostasis and recovery of consciousness. We compared the cases over the 5 year periods before and after the introduction of this revised postsurgical management plan to investigate its effect on postoperative complications. METHODS: This was a retrospective cohort study involving a single pediatric hospital. The subjects were 199 children aged 1-3 years, who underwent palatoplasty between January 2002 and July 2012. Changes in the incidence rates of postoperative complications were statistically examined. RESULTS: There were significantly more postoperative complications among the patients who were extubated in the operating room than among those extubated in the intensive care unit (operating room group, 22/94 cases; intensive care unit group, 10/105 cases; P < 0.01). Serious complications, such as hypoxemia and airway obstruction, also occurred more frequently in the operating room group. CONCLUSION: Extubation in an intensive care unit was possibly associated with a reduction in postoperative complications. PMID- 26545802 TI - Pharmacokinetic Features and Presence of Antidrug Antibodies Associate With Response to Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis. AB - BACKGROUND & AIMS: The pharmacokinetics of infliximab during induction treatment for ulcerative colitis (UC) have not been studied. We investigated serum concentrations of infliximab and the early appearance of antibodies to infliximab (ATI) during induction treatment in patients with moderate-to-severe UC. METHODS: We performed a prospective analysis of 19 consecutive patients with moderate severe UC (endoscopic Mayo >= 2) receiving induction therapy with infliximab (5 mg/kg at weeks 0, 2, and 6) at 2 centers in Amsterdam, The Netherlands, from July 2012 through March 2014. Serial serum and fecal samples were collected for 6 weeks and concentrations of infliximab, ATI, c-reactive protein (CRP), albumin, and fecal calprotectin were measured. Treatment success was defined as endoscopic response (>= 1 point reduction in the endoscopic Mayo score) at week 8. RESULTS: Eleven patients (58%) had an endoscopic response. The median serum concentrations of infliximab at week 6 were 8.1 MUg/mL in responders (interquartile range, 3.0 13.7 MUg/mL) and 2.9 MUg/mL in nonresponders (interquartile range, 0.01-5.8 MUg/mL) (P = .03). ATIs were detected in 7 patients as early as day 18 (median, 28 d; interquartile range, 18-42 d). Six of the 8 nonresponders tested positive for ATIs vs 1 of 11 responders (P < .01; odds ratio, 30.0; 95% CI, 2.2-406.2). Patients with a baseline concentration of CRP greater than 50 mg/L had lower drug exposure from weeks 0 to 6 (587 mg/L/d in patients with high levels of CRP vs 1361 mg/L/day in patients with low CRP; P = .001). The median area under the curve for serum concentration of infliximab during induction therapy was 1230 mg/L/d in nonresponders vs 1352 mg/L/d in responders (P = .65). CONCLUSIONS: There is a significant difference in serum concentration of infliximab at week 6 of treatment between responders and nonresponders. Early development of ATIs during induction therapy reduces the serum concentration of infliximab and is associated with nonresponse to treatment. Patients with high baseline serum levels of CRP had lower serum concentrations of infliximab. CLINICAL TRIAL NUMBER: NL39626.018.12. PMID- 26545803 TI - Gastrointestinal Features of Chronic Granulomatous Disease Found During Endoscopy. AB - BACKGROUND & AIMS: Chronic granulomatous disease (CGD) is an inherited disorder of the reduced nicotinamide adenine dinucleotide phosphate oxidase complex within phagocytic cells that predisposes people to bacterial and fungal infections. Approximately 40% of patients with CGD have gastrointestinal involvement. We aimed to characterize the endoscopic features of gastrointestinal CGD and define the role of endoscopy in patients. METHODS: We created a database of all patients with CGD seen at the National Institutes of Health from 1990 through 2010. We identified patients who had an endoscopy, and collected information from those with CGD-associated inflammatory bowel disease. We analyzed clinical data (demographic information and symptoms), endoscopic data (indication, preparation quality, degree of inflammation, mucosal findings, and complications), and pathologic data. RESULTS: A total of 211 endoscopies (96 esophagogastroduodenoscopies, 82 colonoscopies, and 33 flexible sigmoidoscopies) were performed at the National Institutes of Health on 78 patients with CGD. Esophageal, gastric, and duodenal inflammation were detected in 21%, 74%, and 37% of patients, respectively. Esophageal dysmotility and structural abnormalities were noted in 26%. Of the patients who had colonic CGD-inflammatory bowel disease, 74% had skip lesions and 93% had anorectal disease. Enteric fistulae were found in 18% of patients; 73% of these were perianal. Colonic strictures were observed in 24% of patients; 80% were in the anorectal area. CONCLUSIONS: Based on an analysis of clinical and endoscopic data from 78 patients, CGD inflammatory bowel disease is a distinct entity, primarily involving the anus and rectum, with skip lesions in the remaining bowel. Bowel strictures and fistulae are present in a significant number of patients. Upper gastrointestinal tract inflammatory disease is common, although typically not as severe as colonic disease. Upper and lower endoscopies are important in characterizing the gastrointestinal features of CGD. PMID- 26545805 TI - Surgeons urged to prepare for changes in cosmetic surgery regulation. PMID- 26545804 TI - Policy on palliative care in the WHO European region: an overview of progress since the Council of Europe's (2003) recommendation 24. AB - BACKGROUND: With the goal of achieving greater unity and coherence, the Council of Europe developed a national palliative care (PC) policy framework Recommendation (2003) 24. Although directed at member states, the policy spread to the wider World Health Organisation (WHO) European Region. This article aims to present the current situation relating to national PC health policies in European countries. METHODS: A cross-sectional survey was conducted in 53 European countries of the WHO European Region. Relevant data reported (i) the existence of official documents concerning the provision of PC; (ii) the role of health departments and policymakers in the evaluation of PC provision and (iii) the availability of financial resources for PC provision. RESULTS: In total, 46/53 (87%) EU and non-EU countries responded. PC legislation is established in 20 (71%) EU and nine (50%) non-EU countries. A total of 12 (43%) EU countries possess a PC plan or strategy in comparison with six (33%) non-EU countries. Individuals from Departments of Health and designated policymakers have established collaborative PC efforts. Quality systems have been initiated in 15 (54%) EU and four (22%) non-EU countries. Significant differences were not found in the reporting of payments for PC services between European regions. CONCLUSION: An improvement in national PC policy in both EU and non-EU countries was observed. Future priorities include potential initiatives to improve relationships with policymakers, establish quality control programmes and ensure financial support for PC. PMID- 26545806 TI - First Azospirillum genome from aquatic environments: Whole-genome sequence of Azospirillum thiophilum BV-S(T), a novel diazotroph harboring a capacity of sulfur-chemolithotrophy from a sulfide spring. AB - Azospirillum thiophilum BV-S(T), isolated from a sulfide spring, is a novel nitrogen-fixing bacterium harboring sulfur-lithotrophy. In order to identify genetic characteristics with habitat- and metabolic features contrasting to those from terrestrial Azospirillum species, we present here the genome sequence of a novel species A. thiophilum BV-S(T), with a significance of first genome report in the aquatic Azospirillum species. The genome of strain BV-S(T) is comprised of 7.6Mb chromosome with a GC content of 68.2%. This information will contribute to expand understandings of sulfur-oxidizer microbes that preserve inherencies as a diazotroph, and further it will provide insights into genome plasticity of the genus Azospirillum for niche specific adaptations. PMID- 26545807 TI - Fishing for divergence in a sea of connectivity: The utility of ddRADseq genotyping in a marine invertebrate, the black-lip pearl oyster Pinctada margaritifera. AB - Population genomic investigations on highly dispersive marine organisms typically require thousands of genome-wide SNP loci to resolve fine-scale population structure and detect signatures of selection. This information is important for species conservation efforts and stock management in both wild and captive populations, as well as genome mapping and genome wide association studies. Double digest Restriction site-Associated DNA Sequencing (ddRADseq) is a recent tool for delivering genome wide SNPs for non-model organisms. However, its application to marine invertebrate taxa has been limited, particularly given the complex and highly repetitive nature of many of these organisms' genomes. This study develops and evaluates an optimised ddRADseq technique together with associated analyses for generating genome-wide SNP data, and performs population genomic analyses to inform aquaculture and fishery management of a marine bivalve, the black-lip pearl oyster Pinctada margaritifera. A total of 5243 high quality genome-wide SNP markers were detected, and used to assess population structure, genome diversity, detect Fst outliers and perform association testing in 156 individuals belonging to three wild and one hatchery produced populations from the Fiji Islands. Shallow but significant population structure was revealed among all wild populations (average pairwise Fst=0.046) when visualised with DAPC and an individual network analysis (NetView P), with clear evidence of a genetic bottleneck in the hatchery population (NeLD=6.1), compared to wild populations (NeLD>192.5). Fst outlier detection revealed 42-62 highly differentiated SNPs (p<0.02), while case-control association discovered up to 152 SNPs (p<0.001). Both analyses were able to successfully differentiate individuals between the orange and black tissue colour morphotypes characteristic of this species. BLAST searches revealed that five of these SNPs were associated with a melanin biosynthesis pathway, demonstrating their biological relevance. This study has produced highly informative SNP and population genomic data in P. margaritifera, and using the same approach promises to be of substantial value to a range of other non-model, broadcast-spawning or marine invertebrate taxa. PMID- 26545809 TI - [Keloid scars (part I): Clinical presentation, epidemiology, histology and pathogenesis]. AB - Keloid scars are a dysregulated response to cutaneous wound healing and are characterized by excessive deposition of collagen. Clinical and histological aspects are typical but they are often confused with hypertrophic scars. Principal pathogenesis is abnormal regulation of the collagen equilibrium because of TGFbeta. In this first part, clinical characteristics, physiopathology and histology of keloid scars are explained. PMID- 26545810 TI - CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation. AB - Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3 3sigma) as a CALML5-binding protein. CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation. PMID- 26545808 TI - ATP-binding cassette transporters in reproduction: a new frontier. AB - BACKGROUND: The transmembrane ATP-binding cassette (ABC) transporters actively efflux an array of clinically relevant compounds across biological barriers, and modulate biodistribution of many physiological and pharmacological factors. To date, over 48 ABC transporters have been identified and shown to be directly and indirectly involved in peri-implantation events and fetal/placental development. They efflux cholesterol, steroid hormones, vitamins, cytokines, chemokines, prostaglandins, diverse xenobiotics and environmental toxins, playing a critical role in regulating drug disposition, immunological responses and lipid trafficking, as well as preventing fetal accumulation of drugs and environmental toxins. METHODS: This review examines ABC transporters as important mediators of placental barrier functions and key reproductive processes. Expression, localization and function of all identified ABC transporters were systematically reviewed using PubMed and Google Scholar websites to identify relevant studies examining ABC transporters in reproductive tissues in physiological and pathophysiological states. Only reports written in English were incorporated with no restriction on year of publication. While a major focus has been placed on the human, extensive evidence from animal studies is utilized to describe current understanding of the regulation and function of ABC transporters relevant to human reproduction. RESULTS: ABC transporters are modulators of steroidogenesis, fertilization, implantation, nutrient transport and immunological responses, and function as 'gatekeepers' at various barrier sites (i.e. blood-testes barrier and placenta) against potentially harmful xenobiotic factors, including drugs and environmental toxins. These roles appear to be species dependent and change as a function of gestation and development. The best-described ABC transporters in reproductive tissues (primarily in the placenta) are the multidrug transporters p glycoprotein and breast cancer-related protein, the multidrug resistance proteins 1 through 5 and the cholesterol transporters ABCA1 and ABCG1. CONCLUSIONS: The ABC transporters have various roles across multiple reproductive tissues. Knowledge of efflux direction, tissue distribution, substrate specificity and regulation of the ABC transporters in the placenta and other reproductive tissues is rapidly expanding. This will allow better understanding of the disposition of specific substrates within reproductive tissues, and facilitate development of novel treatments for reproductive disorders as well as improved approaches to protecting the developing fetus. PMID- 26545811 TI - WSB1 promotes tumor metastasis by inducing pVHL degradation. AB - The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1alpha's target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency. PMID- 26545812 TI - The bacterial cell cycle regulator GcrA is a sigma70 cofactor that drives gene expression from a subset of methylated promoters. AB - Cell cycle progression in most organisms requires tightly regulated programs of gene expression. The transcription factors involved typically stimulate gene expression by binding specific DNA sequences in promoters and recruiting RNA polymerase. Here, we found that the essential cell cycle regulator GcrA in Caulobacter crescentus activates the transcription of target genes in a fundamentally different manner. GcrA forms a stable complex with RNA polymerase and localizes to almost all active sigma(70)-dependent promoters in vivo but activates transcription primarily at promoters harboring certain DNA methylation sites. Whereas most transcription factors that contact sigma(70) interact with domain 4, GcrA interfaces with domain 2, the region that binds the -10 element during strand separation. Using kinetic analyses and a reconstituted in vitro transcription assay, we demonstrated that GcrA can stabilize RNA polymerase binding and directly stimulate open complex formation to activate transcription. Guided by these studies, we identified a regulon of ~ 200 genes, providing new insight into the essential functions of GcrA. Collectively, our work reveals a new mechanism for transcriptional regulation, and we discuss the potential benefits of activating transcription by promoting RNA polymerase isomerization rather than recruitment exclusively. PMID- 26545813 TI - LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes. AB - The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is the strongest predictor of integration density in transcription units. Analysis of previously published HIV-1 integration site data showed that integration density in transcription units in mouse embryonic fibroblasts also correlated strongly with intron number, and this correlation was absent in cells lacking LEDGF. Affinity purification showed that LEDGF/p75 is associated with a number of splicing factors, and RNA sequencing (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of the transcription units that have alternative isoforms. Thus, LEDGF/p75 interacts with splicing factors, contributes to exon choice, and directs HIV-1 integration to transcription units that are highly spliced. PMID- 26545816 TI - Dual-Mode Controlled Self-Assembly of TiO2 Nanoparticles Through a Cucurbit[8]uril-Enhanced Radical Cation Dimerization Interaction. AB - The realization of controllable multicomponent self-assembly through reversible supramolecular interactions is a challenging goal, and is an important strategy for the fabrication of switchable nanomaterials. Herein we show that the self assembly of TiO2 nanoparticles (NP) functionalized with methyl viologen can be controlled both by light irradiation and chemical reduction through cucurbit[8]uril-enhanced radical cation dimerization interactions. Moreover, the controlled assembly and disassembly of this system are accompanied by switchable photocatalytic activity of the TiO2 NPs, which shows potential application as a novel smart and recyclable photocatalyst. PMID- 26545814 TI - Biochemical identification of new proteins involved in splicing repression at the Drosophila P-element exonic splicing silencer. AB - Splicing of the Drosophila P-element third intron (IVS3) is repressed in somatic tissues due to the function of an exonic splicing silencer (ESS) complex present on the 5' exon RNA. To comprehensively characterize the mechanisms of this alternative splicing regulation, we used biochemical fractionation and affinity purification to isolate the silencer complex assembled in vitro and identify the constituent proteins by mass spectrometry. Functional assays using splicing reporter minigenes identified the proteins hrp36 and hrp38 and the cytoplasmic poly(A)-binding protein PABPC1 as novel functional components of the splicing silencer. hrp48, PSI, and PABPC1 have high-affinity RNA-binding sites on the P element IVS3 5' exon, whereas hrp36 and hrp38 proteins bind with low affinity to the P-element silencer RNA. RNA pull-down and immobilized protein assays showed that hrp48 protein binding to the silencer RNA can recruit hrp36 and hrp38. These studies identified additional components that function at the P-element ESS and indicated that proteins with low-affinity RNA-binding sites can be recruited in a functional manner through interactions with a protein bound to RNA at a high affinity binding site. These studies have implications for the role of heterogeneous nuclear ribonucleoproteins (hnRNPs) in the control of alternative splicing at cis-acting regulatory sites. PMID- 26545815 TI - Transcription and imprinting dynamics in developing postnatal male germline stem cells. AB - Postnatal spermatogonial stem cells (SSCs) progress through proliferative and developmental stages to populate the testicular niche prior to productive spermatogenesis. To better understand, we conducted extensive genomic profiling at multiple postnatal stages on subpopulations enriched for particular markers (THY1, KIT, OCT4, ID4, or GFRa1). Overall, our profiles suggest three broad populations of spermatogonia in juveniles: (1) epithelial-like spermatogonia (THY1(+); high OCT4, ID4, and GFRa1), (2) more abundant mesenchymal-like spermatogonia (THY1(+); moderate OCT4 and ID4; high mesenchymal markers), and (3) (in older juveniles) abundant spermatogonia committing to gametogenesis (high KIT(+)). Epithelial-like spermatogonia displayed the expected imprinting patterns, but, surprisingly, mesenchymal-like spermatogonia lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Furthermore, mesenchymal-like spermatogonia also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes (e.g., protocadherins and olfactory receptors). We also reveal novel candidate receptor-ligand networks involving SSCs and the developing niche. Taken together, neonates/juveniles contain heterogeneous epithelial-like or mesenchymal-like spermatogonial populations, with the latter displaying extensive DNA methylation/chromatin dynamics. We speculate that this plasticity helps SSCs proliferate and migrate within the developing seminiferous tubule, with proper niche interaction and membrane attachment reverting mesenchymal-like spermatogonial subtype cells back to an epithelial-like state with normal imprinting profiles. PMID- 26545817 TI - Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats. AB - In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a 'dominant' role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems. PMID- 26545818 TI - Prospective Cohort Study Evaluating the Prognostic Value of Simple EEG Parameters in Postanoxic Coma. AB - We prospectively studied early bedside standard EEG characteristics in 61 acute postanoxic coma patients. Five simple EEG features, namely, isoelectric, discontinuous, nonreactive to intense auditory and nociceptive stimuli, dominant delta frequency, and occurrence of paroxysms were classified yes or no. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of each of these variables for predicting an unfavorable outcome, defined as death, persistent vegetative state, minimally conscious state, or severe neurological disability, as assessed 1 year after coma onset were computed as well as Synek's score. The outcome was unfavorable in 56 (91.8%) patients. Sensitivity, specificity, PPV, NPV, and AUC of nonreactive EEG for predicting an unfavorable outcome were 84%, 80%, 98%, 31%, and 0.82, respectively; and were all very close to the ones of Synek score>3, which were 82%, 80%, 98%, 29%, and 0.81, respectively. Specificities for predicting an unfavorable outcome were 100% for isoelectric, discontinuous, or dominant delta activity EEG. These 3 last features were constantly associated to unfavorable outcome. Absent EEG reactivity strongly predicted an unfavorable outcome in postanoxic coma, and performed as accurate as a Synek score>3. Analyzing characteristics of some simple EEG features may easily help nonneurophysiologist physicians to investigate prognostic issue of postanoxic coma patient. In this study (a) discontinuous, isoelectric, or delta dominant EEG were constantly associated with unfavorable outcome and (b) nonreactive EEG performed prognostic as accurate as a Synek score>3. PMID- 26545819 TI - Resting State EEG in Children With Learning Disabilities: An Independent Component Analysis Approach. AB - In this study, the neurophysiological underpinnings of learning disabilities (LD) in children are examined using resting state EEG. We were particularly interested in the neurophysiological differences between children with learning disabilities not otherwise specified (LD-NOS), learning disabilities with verbal disabilities (LD-Verbal), and healthy control (HC) children. We applied 2 different approaches to examine the differences between the different groups. First, we calculated theta/beta and theta/alpha ratios in order to quantify the relationship between slow and fast EEG oscillations. Second, we used a recently developed method for analyzing spectral EEG, namely the group independent component analysis (gICA) model. Using these measures, we identified substantial differences between LD and HC children and between LD-NOS and LD-Verbal children in terms of their spectral EEG profiles. We obtained the following findings: (a) theta/beta and theta/alpha ratios were substantially larger in LD than in HC children, with no difference between LD-NOS and LD-Verbal children; (b) there was substantial slowing of EEG oscillations, especially for gICs located in frontal scalp positions, with LD-NOS children demonstrating the strongest slowing; (c) the estimated intracortical sources of these gICs were mostly located in brain areas involved in the control of executive functions, attention, planning, and language; and (d) the LD-Verbal children demonstrated substantial differences in EEG oscillations compared with LD-NOS children, and these differences were localized in language-related brain areas. The general pattern of atypical neurophysiological activation found in LD children suggests that they suffer from neurophysiological dysfunction in brain areas involved with the control of attention, executive functions, planning, and language functions. LD-Verbal children also demonstrate atypical activation, especially in language-related brain areas. These atypical neurophysiological activation patterns might provide a helpful guide for rehabilitation strategies to treat the deficiencies in these children with LD. PMID- 26545820 TI - Probabilistic models of genetic variation in structured populations applied to global human studies. AB - MOTIVATION: Modern population genetics studies typically involve genome-wide genotyping of individuals from a diverse network of ancestries. An important problem is how to formulate and estimate probabilistic models of observed genotypes that account for complex population structure. The most prominent work on this problem has focused on estimating a model of admixture proportions of ancestral populations for each individual. Here, we instead focus on modeling variation of the genotypes without requiring a higher-level admixture interpretation. RESULTS: We formulate two general probabilistic models, and we propose computationally efficient algorithms to estimate them. First, we show how principal component analysis can be utilized to estimate a general model that includes the well-known Pritchard-Stephens-Donnelly admixture model as a special case. Noting some drawbacks of this approach, we introduce a new 'logistic factor analysis' framework that seeks to directly model the logit transformation of probabilities underlying observed genotypes in terms of latent variables that capture population structure. We demonstrate these advances on data from the Human Genome Diversity Panel and 1000 Genomes Project, where we are able to identify SNPs that are highly differentiated with respect to structure while making minimal modeling assumptions. AVAILABILITY AND IMPLEMENTATION: A Bioconductor R package called lfa is available at http://www.bioconductor.org/packages/release/bioc/html/lfa.html CONTACT: jstorey@princeton.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26545821 TI - De novo identification of replication-timing domains in the human genome by deep learning. AB - MOTIVATION: The de novo identification of the initiation and termination zones regions that replicate earlier or later than their upstream and downstream neighbours, respectively-remains a key challenge in DNA replication. RESULTS: Building on advances in deep learning, we developed a novel hybrid architecture combining a pre-trained, deep neural network and a hidden Markov model (DNN-HMM) for the de novo identification of replication domains using replication timing profiles. Our results demonstrate that DNN-HMM can significantly outperform strong, discriminatively trained Gaussian mixture model-HMM (GMM-HMM) systems and other six reported methods that can be applied to this challenge. We applied our trained DNN-HMM to identify distinct replication domain types, namely the early replication domain (ERD), the down transition zone (DTZ), the late replication domain (LRD) and the up transition zone (UTZ), using newly replicated DNA sequencing (Repli-Seq) data across 15 human cells. A subsequent integrative analysis revealed that these replication domains harbour unique genomic and epigenetic patterns, transcriptional activity and higher-order chromosomal structure. Our findings support the 'replication-domain' model, which states (1) that ERDs and LRDs, connected by UTZs and DTZs, are spatially compartmentalized structural and functional units of higher-order chromosomal structure, (2) that the adjacent DTZ-UTZ pairs form chromatin loops and (3) that intra-interactions within ERDs and LRDs tend to be short-range and long-range, respectively. Our model reveals an important chromatin organizational principle of the human genome and represents a critical step towards understanding the mechanisms regulating replication timing. AVAILABILITY AND IMPLEMENTATION: Our DNN-HMM method and three additional algorithms can be freely accessed at https://github.com/wenjiegroup/DNN-HMM The replication domain regions identified in this study are available in GEO under the accession ID GSE53984. CONTACT: shuwj@bmi.ac.cn or boxc@bmi.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26545822 TI - Comparison of genetic variants in matched samples using thesaurus annotation. AB - MOTIVATION: Calling changes in DNA, e.g. as a result of somatic events in cancer, requires analysis of multiple matched sequenced samples. Events in low mappability regions of the human genome are difficult to encode in variant call files and have been under-reported as a result. However, they can be described accurately through thesaurus annotation-a technique that links multiple genomic loci together to explicate a single variant. RESULTS: We here describe software and benchmarks for using thesaurus annotation to detect point changes in DNA from matched samples. In benchmarks on matched normal/tumor samples we show that the technique can recover between five and ten percent more true events than conventional approaches, while strictly limiting false discovery and being fully consistent with popular variant analysis workflows. We also demonstrate the utility of the approach for analysis of de novo mutations in parents/child families. AVAILABILITY AND IMPLEMENTATION: Software performing thesaurus annotation is implemented in java; available in source code on github at GeneticThesaurus (https://github.com/tkonopka/GeneticThesaurus) and as an executable on sourceforge at geneticthesaurus (https://sourceforge.net/projects/geneticthesaurus). Mutation calling is implemented in an R package available on github at RGeneticThesaurus (https://github.com/tkonopka/RGeneticThesaurus). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: tomasz.konopka@ludwig.ox.ac.uk. PMID- 26545823 TI - Evaluation of hierarchical models for integrative genomic analyses. AB - MOTIVATION: Advances in high-throughput technologies have led to the acquisition of various types of -omic data on the same biological samples. Each data type gives independent and complementary information that can explain the biological mechanisms of interest. While several studies performing independent analyses of each dataset have led to significant results, a better understanding of complex biological mechanisms requires an integrative analysis of different sources of data. RESULTS: Flexible modeling approaches, based on penalized likelihood methods and expectation-maximization (EM) algorithms, are studied and tested under various biological relationship scenarios between the different molecular features and their effects on a clinical outcome. The models are applied to genomic datasets from two cancer types in the Cancer Genome Atlas project: glioblastoma multiforme and ovarian serous cystadenocarcinoma. The integrative models lead to improved model fit and predictive performance. They also provide a better understanding of the biological mechanisms underlying patients' survival. AVAILABILITY AND IMPLEMENTATION: Source code implementing the integrative models is freely available at https://github.com/mgt000/IntegrativeAnalysis along with example datasets and sample R script applying the models to these data. The TCGA datasets used for analysis are publicly available at https://tcga data.nci.nih.gov/tcga/tcgaDownload.jsp CONTACT: marie.denis@cirad.fr or mgt26@georgetown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26545824 TI - Automatic generation of bioinformatics tools for predicting protein-ligand binding sites. AB - MOTIVATION: Predictive tools that model protein-ligand binding on demand are needed to promote ligand research in an innovative drug-design environment. However, it takes considerable time and effort to develop predictive tools that can be applied to individual ligands. An automated production pipeline that can rapidly and efficiently develop user-friendly protein-ligand binding predictive tools would be useful. RESULTS: We developed a system for automatically generating protein-ligand binding predictions. Implementation of this system in a pipeline of Semantic Web technique-based web tools will allow users to specify a ligand and receive the tool within 0.5-1 day. We demonstrated high prediction accuracy for three machine learning algorithms and eight ligands. AVAILABILITY AND IMPLEMENTATION: The source code and web application are freely available for download at http://utprot.net They are implemented in Python and supported on Linux. CONTACT: shimizu@bi.a.u-tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26545826 TI - Blood donation mobile applications: are donors ready? AB - BACKGROUND: The rapid rise of mobile communication technologies has the potential to dramatically change and improve blood donor recruitment and retention efforts. STUDY DESIGN AND METHODS: E-mail invitations were sent to blood donors in a large metropolitan area to participate in a Web-based survey designed to gauge their readiness and interest level for a blood donation mobile application ("app"). RESULTS: A total of 982 ethnically diverse respondents of various age groups and prior donation experiences were surveyed. Among the respondents, 87.3% had ready access to smart phones. E-mail was chosen by 62.1% as the currently preferred method when contacted by the blood center, followed by texting (10.1%). App features desired by most respondents were the abilities to request appointments 24/7 (76.8%) and to receive appointment confirmations quickly (81.3%). Many were concerned about receiving too many alerts or messages (64.1%) or insufficient protection for personal information (53.5%). Overall, 67.7% of respondents indicated that they were likely to use a blood donation mobile app. Likelihood was not significantly different by sex or ethnicity, and the impact of education level was limited. Donors who currently made donation appointments via telephone or a website were equally likely to use such an app. However, donors older than 45 years were less likely than younger donors (p = 0.001), and donors with more than five lifetime donations were more likely than less frequent donors to use such an app (p = 0.02). CONCLUSION: In a metropolitan area, donors are very receptive to using a mobile app to manage their donations. PMID- 26545825 TI - 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. AB - OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (>=6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies. PMID- 26545827 TI - A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors. AB - Pyrrolidine-based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O-GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O-GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O GlcNAc, and should prove useful tools for studying the role of OGA in health and disease. PMID- 26545828 TI - Practical impacts of genomic data "cleaning" on biological discovery using surrogate variable analysis. AB - BACKGROUND: Genomic data production is at its highest level and continues to increase, making available novel primary data and existing public data to researchers for exploration. Here we explore the consequences of "batch" correction for biological discovery in two publicly available expression datasets. We consider this to include the estimation of and adjustment for wide spread systematic heterogeneity in genomic measurements that is unrelated to the effects under study, whether it be technical or biological in nature. METHODS: We present three illustrative data analyses using surrogate variable analysis (SVA) and describe how to perform artifact discovery in light of natural heterogeneity within biological groups, secondary biological questions of interest, and non linear treatment effects in a dataset profiling differentiating pluripotent cells (GSE32923) and another from human brain tissue (GSE30272). RESULTS: Careful specification of biological effects of interest is very important to factor-based approaches like SVA. We demonstrate greatly sharpened global and gene-specific differential expression across treatment groups in stem cell systems. Similarly, we demonstrate how to preserve major non-linear effects of age across the lifespan in the brain dataset. However, the gains in precisely defining known effects of interest come at the cost of much other information in the "cleaned" data, including sex, common copy number effects and sample or cell line-specific molecular behavior. CONCLUSIONS: Our analyses indicate that data "cleaning" can be an important component of high-throughput genomic data analysis when interrogating explicitly defined effects in the context of data affected by robust technical artifacts. However, caution should be exercised to avoid removing biological signal of interest. It is also important to note that open data exploration is not possible after such supervised "cleaning", because effects beyond those stipulated by the researcher may have been removed. With the goal of making these statistical algorithms more powerful and transparent to researchers in the biological sciences, we provide exploratory plots and accompanying R code for identifying and guiding "cleaning" process (https://github.com/andrewejaffe/StemCellSVA). The impact of these methods is significant enough that we have made newly processed data available for the brain data set at http://braincloud.jhmi.edu/plots/ and GSE30272. PMID- 26545829 TI - Letter to the editor regarding: The effect of cloth stoma covers on tracheal climate of laryngectomy patients. PMID- 26545830 TI - Development of a new disease severity scoring system for patients with non transfusion-dependent thalassemia. AB - BACKGROUND: Patients with non-transfusion-dependent thalassemia (NTDT) present with a spectrum of disease severities. Since there are multiple pathophysiologies in such patients, tailoring treatment remains essential. Therefore, one simple, reliable tool would be beneficial to assess disease severity and tailor therapy, particularly for internal medicine specialists who may treat a variety of NTDT patients with a multitude of complications. This would allow for standardization of assessments leading to timely interventions and prevention of complications. METHODS: A working group of NTDT experts was formed to develop a new disease severity scoring system for adult and pediatric patients with NTDT, based on parameters considered to be most pertinent in defining disease severity. RESULTS: 20 parameters were selected for inclusion in the disease severity scoring system. An additional six parameters, largely related to growth and development, were selected specifically for pediatric patients (<= 16 years of age). Consensus of expert opinion was used to establish the selected methods of assessment for each parameter, based on feasibility and availability of technology, cost containment, and avoidance of patient risk. CONCLUSION: We propose that this new disease severity scoring system for adult and pediatric NTDT patients could be developed into a practical tool for widespread clinical use. PMID- 26545831 TI - Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. AB - Inhibition of GABAergic neural inputs to dorsal columns of the periaqueductal grey matter (dPAG), posterior (PH) and dorsomedial (DMH) hypothalamic nuclei elicits distinct types of escape behavioural reactions. To differentiate between the variety and intensity of panic-related behaviours, the pattern of defensive behaviours evoked by blockade of GABAA receptors in the DMH, PH and dPAG were compared in a circular open-field test and in a recently designed polygonal arena. In the circular open-field, the defensive behaviours induced by microinjection of bicuculline into DMH and PH were characterised by defensive alertness behaviour and vertical jumps preceded by rearing exploratory behaviour. On the other hand, explosive escape responses interspersed with horizontal jumps and freezing were observed after the blockade of GABAA receptors on dPAG neurons. In the polygonal arena apparatus, the escape response produced by GABAergic inhibition of DMH and PH neurons was directed towards the burrow. In contrast, the blockade of GABAA receptors in dPAG evoked non-oriented escape behaviour characterised by vigorous running and horizontal jumps in the arena. Our findings support the hypothesis that the hypothalamic nuclei organise oriented escape behavioural responses whereas non-oriented escape is elaborated by dPAG neurons. Additionally, the polygonal arena with a burrow made it easy to discriminate and characterise these two different patterns of escape behavioural responses. In this sense, the polygonal arena with a burrow can be considered a good methodological tool to discriminate between these two different patterns of escape behavioural responses and is very useful as a new experimental animal model of panic attacks. PMID- 26545832 TI - Pitocin and autism: An analysis of oxytocin receptor desensitization in the fetus. AB - The risk of Pitocin as a cause of autism attributable to oxytocin receptor desensitization in the brain of the fetus is evaluated in terms of a mathematical model. A composite unit, D, for oxytocin receptor desensitization levels is established with the form ((IU-h)/ml)E-3, where IU is the international unit for oxytocin. The desensitization values for oxytocin receptor desensitization at a concentration of 10 nmol of oxytocin per liter for 3, 4.2 and 6h corresponding to 0%, 50% and 100% desensitization are calculated to be 15 D, 21 D, and 30 D, respectively. The permeability of the blood-brain barrier in the fetus to oxytocin is discussed, and the upper limit of the concentration of Pitocin in the placenta, and its possible diffusion into the blood and brain of the fetus, is calculated for a routine dose of 6 milli U per minute of Pitocin over a 12h labor. This dose of Pitocin is shown to result in a desensitization value in units of D that is more than a factor of 10 below the 0% desensitization value of 15 D. This indicates that routine doses of Pitocin are not a significant cause of autism attributable to oxytocin receptor desensitization. This is consistent with the findings of a major epidemiological study of the association of Pitocin with autism in Denmark entitled, "Oxytocin-augmented labor and risk for males", Behavioral Brain Research, May 1, 2015; 284:207-212, which found no association between the use of Pitocin during labor and the incidence of autism for females, and a modest association for males. PMID- 26545833 TI - Rethinking traditional Chinese medicines for cancer. PMID- 26545834 TI - Busulfan-based conditioning regimens: not all partners are equal. PMID- 26545835 TI - Morcellation of uterine leiomyomas: a plea for patient triage. PMID- 26545836 TI - Abnormal Results. PMID- 26545837 TI - Miss You Already. PMID- 26545839 TI - Correction to Lancet Oncol 2015; 16: 1013. PMID- 26545838 TI - Endometrial cancer with progestagen and oestrogen oral contraceptives. PMID- 26545840 TI - Correction to Lancet Oncol 2015; 16: 1143. PMID- 26545841 TI - Correction to Lancet Oncol 2015; 16: 1289. PMID- 26545843 TI - Multifunctional receptor-targeting antibodies for cancer therapy. AB - During the past decade, monospecific antibodies targeting cell-surface receptors in different tumour types have achieved substantial success and have been at the forefront of cancer treatment. However, redundant signalling and crosstalk between different pathways within tumour cells and between tumour cells and their microenvironment can limit the efficacy of receptor-targeted monospecific-based therapies. Advances in antibody engineering technologies have enabled strategies that simultaneously target multiple receptors to circumvent the limitations of conventional monospecific therapies and achieve enhanced therapeutic efficacy. In the past 5 years, a range of multifunctional, receptor-targeting, antibody-based molecules have emerged, which allow targeting of multiple surface receptors on tumour cells and endothelial or immune cells in the tumour microenvironment. In this Review, we discuss the rationales and strategies for the use of multifunctional receptor-targeting antibodies, their mechanisms of action, and the promises and challenges they hold as cancer therapeutics. This knowledge provides opportunities to improve current targeted therapy outcomes for patients with cancer. PMID- 26545842 TI - Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. AB - Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate. PMID- 26545844 TI - Double-hit and double-protein-expression lymphomas: aggressive and refractory lymphomas. AB - Double-hit lymphoma (DHL) is a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course that is refractory to aggressive treatment and short survival. Over time, the definition was modified and now includes diffuse large B-cell lymphoma (DLBCL) with MYC translocation combined with an additional translocation involving BCL2 or BCL6. Some cases that have a similar clinical course with concomitant overexpression of MYC or BCL2 proteins were recently characterised as immunohistochemical double-hit lymphomas (ie, double-protein-expression lymphomas [DPLs]). The clinical course of these DPLs is worse than so-called standard DLBCL but suggested by some studies to be slightly better than DHL, although there is overlap between the two categories. Present treatment does not allow cure or long term survival in patients with genetic or immunohistochemical double-hit lymphomas, but several new drugs are being developed. PMID- 26545845 TI - Inflammatory breast cancer: unique biological and therapeutic considerations. AB - Through the concerted efforts of many patients, health-care providers, legislators, and other supporters, the past decade has seen the development of the first clinics dedicated to the care of patients with inflammatory breast cancer in the USA and other countries. Together with social networking, advocacy, and education, a few specialised centres have had substantial increases in patient numbers (in some cases ten times higher), which has further expanded the community of science and advocacy and increased the understanding of the disease process. Although inflammatory breast cancer is considered rare, constituting only 2-4% of breast cancer cases, poor prognosis means that patients with the disease account for roughly 10% of breast cancer mortality annually in the USA. I propose that the unique presentation of inflammatory breast cancer might require specific, identifiable changes in the breast parenchyma that occur before the tumour-initiating event. This would make the breast tissue itself a tumour promoting medium that should be treated as a component of the pathology in multidisciplinary treatment and should be further studied for complementary targets to inhibit the pathobiology that is specific to inflammatory breast cancer. PMID- 26545846 TI - Investigation of Clostridium difficile interspecies relatedness using multilocus sequence typing, multilocus variable-number tandem-repeat analysis and antimicrobial susceptibility testing. AB - Multilocus sequence typing (MLST), multilocus variable-number tandem-repeat analysis (MLVA) and antimicrobial susceptibility were performed on 37 animal and human C. difficile isolates belonging to 15 different PCR-ribotypes in order to investigate the relatedness of human and animal isolates and to identify possible transmission routes. MLVA identified a total of 21 different types while MLST only distinguished 12 types. Identical C. difficile strains were detected in the same animal species for PCR-ribotypes 014, 078, UCL 16U and UCL 36, irrespective of their origin or the isolation date. Non clonal strains were found among different hosts; however, a high genetic association between pig and cattle isolates belonging to PCR-ribotype 078 was revealed. MLVA also showed genetic differences that clearly distinguished human from animal strains. For a given PCR ribotype, human and animal strains presented a similar susceptibility to the antimicrobials tested. All strains were susceptible to vancomycin, metronidazole, chloramphenicol and rifampicin, while PCR-ribotypes 078, UCL 5a, UCL 36 and UCL 103 were associated with erythromycin resistance. The data suggest a wide dissemination of clones at hospitals and breeding-farms or a contamination at the slaughterhouse, but less probability of interspecies transmission. However, further highly discriminatory genotyping methods are necessary to elucidate interspecies and zoonotic transmission of C. difficile. PMID- 26545847 TI - Cancer immunotherapy in veterinary medicine: Current options and new developments. AB - Excitement in the field of tumor immunotherapy is being driven by several remarkable breakthroughs in recent years. This review will cover recent advances in cancer immunotherapy, including the use of T cell checkpoint inhibitors, engineered T cells, cancer vaccines, and anti-B cell and T cell antibodies. Inhibition of T cell checkpoint molecules such as PD-1 and CTLA-4 using monoclonal antibodies has achieved notable success against advanced tumors in humans, including melanoma, renal cell carcinoma, and non-small cell lung cancer. Therapy with engineered T cells has also demonstrated remarkable tumor control and regression in human trials. Autologous cancer vaccines have recently demonstrated impressive prolongation of disease-free intervals and survival times in dogs with lymphoma. In addition, caninized monoclonal antibodies targeting CD20 and CD52 just recently received either full (CD20) or conditional (CD52) licensing by the United States Department of Agriculture for clinical use in the treatment of canine B-cell and T-cell lymphomas, respectively. Thus, immunotherapy for cancer is rapidly moving to the forefront of cancer treatment options in veterinary medicine as well as human medicine. PMID- 26545848 TI - Identification of two phylogenetic lineages of equine hepacivirus and high prevalence in Brazil. AB - Non-primate hepacivirus (NPHV), as described in horses, is the virus most genetically related to hepatitis C virus (HCV). Although detected worldwide, limited data on genomic variability and distribution of NPHV are available in Latin America. The aim of this study was to investigate the genetic diversity and prevalence of equine NPHV in Brazil. Thirteen percent of 202 equines from three Brazilian states were positive for NPHV genome by reverse transcriptase PCR. Nucleotide sequences of the partial NS5B genome presented the greatest diversity described to date (25.6%), which is comparable to the upper limit of diversity for HCV subtype classification for the same region. Phylogenetic analysis revealed that Brazilian NPHV sequences along with isolates worldwide form two strongly supported clades (pp = 1.0) suggesting the existence of two distinct lineages. PMID- 26545849 TI - Presence of Magnetic Resonance Imaging Suspicious Lesion Predicts Gleason 7 or Greater Prostate Cancer in Biopsy-Naive Patients. AB - OBJECTIVE: To compare the relative value of magnetic resonance imaging (MRI) in biopsy-naive patients to those with previous negative biopsy. Although MRI targeted biopsy has been studied in several major prostate cancer (PCa) cohorts (biopsy naive, previous negative biopsy, and active surveillance), the relative benefit in these cohorts has not been established. METHODS: We retrospectively reviewed biopsy-naive (n = 45) and previous negative biopsy (n = 55) patients who underwent prostate MRI prior to biopsy at our institution. Patients with an MRI suspicious region (MSR) underwent MRI-targeted biopsy as well as a systematic template biopsy, whereas those without MSR underwent only the template biopsy. All biopsies were performed with the TargetScan (Envisioneering, Pittsburgh, PA) biopsy system. MRI targeting was performed with cognitive guidance. RESULTS: On multivariate logistic regression, the presence of an MSR was the only statistically significant and independent predictor of Gleason >= 7 PCa on biopsy for biopsy-naive men (odds ratio [OR] 40.2, P = .01). For men with previous negative biopsy, the presence of MSR was not a predictor of Gleason >= 7 PCa on biopsy (OR 4.35, P = .16), whereas PSA density > 0.15 ng/mL(2) was a significant and independent predictor (OR 66.2, P < .01). CONCLUSION: Prostate MRI should be considered prior to biopsy in all patients presenting with clinical suspicion for PCa, as presence of a MSR will help guide prebiopsy counseling and provide an opportunity for MRI targeting during biopsy. PMID- 26545850 TI - Is Ureteroscopy Needed Prior to Nephroureterectomy? An Evidence-Based Algorithmic Approach. AB - OBJECTIVE: To develop an evidence-based approach to the diagnostic workup of suspicious upper urinary tract lesions. METHODS: The PubMed database was searched using the following terms with a filter for English language: "upper tract urothelial carcinoma" and "upper tract transitional cell carcinoma," along with the following corresponding terms: "cost," "epidemiology," "diagnosis," "ureteroscopy," and "workup." A total of 404 articles were returned, and 33 were reviewed in full based on relevance. RESULTS: Computed tomography urogram is both sensitive and specific (96% and 99%). Cytology is utilized for its specificity (89%-100%). Ureteroscopy and biopsy of an upper tract lesion can be helpful in equivocal cases but can pose challenges in terms of yield and eventual pathologic upstaging. Due to the high sensitivity and specificity of other noninvasive tests, ureteroscopy can be obviated in select cases. We assess the available evidence and devise an algorithm for the evaluation of an upper tract urothelial carcinoma lesion. CONCLUSION: Ureteroscopy can be omitted as part of the diagnostic workup in appropriately selected cases of upper tract urothelial carcinoma. PMID- 26545851 TI - Esterase and peroxidase isoforms in different stages of morphogenesis in Fritillaria meleagris L. in bulb-scale culture. AB - Morphogenesis in vitro is a complex and still poorly defined process. We investigated esterase and peroxidase isoforms detected in bulb scale, during Fritillaria meleagris morphogenesis. Bulbs were grown either at 4 degrees C or on a medium with an increased concentration of sucrose (4.5%) for 30 days. After these pre-treatments, the bulb scales were further grown on nutrient media that contained different concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin (KIN) or thidiazuron (TDZ). Regeneration of somatic embryos and bulblets occurred at the same explant. The highest numbers of somatic embryos and bulblets were regenerated on the medium containing 2,4-D and KIN (1mg/L each), while morphogenesis was most successful at a TDZ concentration between 0.5 and 1mg/L. Monitoring of esterases and peroxidases was performed by growing bulb scales on a medium enriched with 2,4-D and KIN or TDZ (1mg/L), and the number and activity of isoforms were followed every 7 days for 4 weeks. In control explants, six isoforms of esterase were observed. Three isoforms of peroxidase were not detected in the control bulb scale, which has not begun its morphogenesis process. PMID- 26545852 TI - Implementing Value-Based Payment Reform: A Conceptual Framework and Case Examples. AB - This article develops a conceptual framework for implementation of value-based payment (VBP) reform and then draws on that framework to systematically examine six distinct multi-stakeholder coalition VBP initiatives in three different regions of the United States. The VBP initiatives deploy the following payment models: reference pricing, "shadow" primary care capitation, bundled payment, pay for performance, shared savings within accountable care organizations, and global payment. The conceptual framework synthesizes prior models of VBP implementation. It describes how context, project objectives, payment and care delivery strategies, and the barriers and facilitators to translating strategy into implementation affect VBP implementation and value for patients. We next apply the framework to six case examples of implementation, and conclude by discussing the implications of the case examples and the conceptual framework for future practice and research. PMID- 26545853 TI - Mood as Representation of Momentum. AB - Experiences affect mood, which in turn affects subsequent experiences. Recent studies suggest two specific principles. First, mood depends on how recent reward outcomes differ from expectations. Second, mood biases the way we perceive outcomes (e.g., rewards), and this bias affects learning about those outcomes. We propose that this two-way interaction serves to mitigate inefficiencies in the application of reinforcement learning to real-world problems. Specifically, we propose that mood represents the overall momentum of recent outcomes, and its biasing influence on the perception of outcomes 'corrects' learning to account for environmental dependencies. We describe potential dysfunctions of this adaptive mechanism that might contribute to the symptoms of mood disorders. PMID- 26545854 TI - [Management of breast nipple discharge: Recommendations]. AB - OBJECTIVES: To investigate diagnostic value of imaging procedures and management strategies of the patients with nipple discharge (ND) to establish management recommendations. METHODS: Bibliographical search in French and English languages by consultation of PubMed, Cochrane and Embase databases. RESULTS: Although, all ND require an systematic evaluation guided by clinical data, bloody ND could be a predictor of breast cancer risk among different colors of discharge particularly in patients of more than 50 years (LE2). The mammography and breast ultrasography are the imaging procedures to realize in first intention (grade C) but they turn out useful only when they detect radiological abnormalities (LE4). Galactography has only a localizing value of possible ductal abnormalities (when standard imaging procedures is not contributive) (LE4). Thus, in the diagnostic investigation of a suspicious ND, galactography it is not recommended in standard practice (grade C). The breast Magnetic Resonance Imaging (MRI) is recommended when breast standard imaging procedures are not contributive (grade C). The ND cytology is useful only if it is positive (i.e. reveal cancer cells). There is no proof on the diagnostic performance of the cytological analysis of the ND to allow a recommendation on its realization or not. In front of a suspicious ND, when breast-imaging procedures reveals an associated radiological lesion, an adapted percutaneous biopsy is recommended by percutaneous way (grade C). Vacuum assisted breast biopsies is a diagnostic tool but can also be therapeutic allowing to avoid surgery in case of benign lesion but current literature data do not allow recommendations on the therapeutic aspect of vacuum-assisted breast biopsy (LE4). In the absence of associated radiological signal, and in case of reproducible bloody persistent ND, a pyramidectomy is recommended (grade C). PMID- 26545855 TI - [Breastfeeding (part one): Frequency, benefits and drawbacks, optimal duration and factors influencing its initiation and prolongation. Clinical guidelines for practice]. AB - OBJECTIVES: The objectives were to on assess the frequency and the duration of breastfeeding in France. On the other hand, the objectives were to identify its benefits and drawbacks, and to study the factors influencing its initiation and its extension. MATERIAL AND METHODS: Bibliographic research in Medline, Google Scholar and in the Cochrane Library. RESULTS: Breastfeeding concerns in France about 70% of children at birth (EL2). Its median duration is about 15 weeks and 3 weeks 1/2 for exclusive breastfeeding. At three months, only one third of children breastfed at birth are still being breastfed (EL2). Whether this is due to the composition of breast milk or the behavior of mothers with their children or their socio-cultural level, or even by all these components at once, breastfeeding is associated with better cognitive development children (EL2). This effect is even more reinforced that mothers breastfeed exclusively and prolonged (EL2). As part of the prevention of many diseases (ear infections, gastrointestinal infections, atopic diseases, obesity and cardiovascular diseases...), exclusive and prolonged breastfeeding (grade B) between 4 to 6 months is recommended (professional consensus). Breastfeeding is not a means of preventing postpartum depression (professional consensus). To reduce the incidence of breast cancer, prolonged breastfeeding is recommended (grade B). In order to increase the rate of initiation of breastfeeding as well as its duration, it is recommended that health professionals work closely with mothers in their project (grade A), the breastfeeding promotion messages include message to husbands (grade B), and to promote breastfeeding on demand without fixed interval between feedings (grade B). However, there is not enough data to recommend the use of a specific position during breastfeeding, or the use of one or two breast or to early start breastfeeding or not (professional consensus). CONCLUSION: Exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (professional consensus). PMID- 26545856 TI - [Benign proliferative breast disease with and without atypia]. AB - In the last few years, diagnostics of high-risk breast lesions (atypical ductal hyperplasia [ADH], flat epithelial atypia [FEA], lobular neoplasia: atypical lobular hyperplasia [ALH], lobular carcinoma in situ [LCIS], radial scar [RS], usual ductal hyperplasia [UDH], adenosis, sclerosing adenosis [SA], papillary breast lesions, mucocele-like lesion [MLL]) have increased with the growing number of breast percutaneous biopsies. The management of these lesions is highly conditioned by the enlarged risk of breast cancer combined with either an increased probability of finding cancer after surgery, either a possible malignant transformation (in situ or invasive cancer), or an increased probability of developing cancer on the long range. An overview of the literature reports grade C recommendations concerning the management and follow-up of these lesions: in case of ADH, FEA, ALH, LCIS, RS, MLL with atypia, diagnosed on percutaneous biopsies: surgical excision is recommended; in case of a diagnostic based on vacuum-assisted core biopsy with complete disappearance of radiological signal for FEA or RS without atypia: surgical abstention is a valid alternative approved by multidisciplinary meeting. In case of ALH (incidental finding) associated with benign lesion responsible of radiological signal: abstention may be proposed; in case of UDH, adenosis, MLL without atypia, diagnosed on percutaneous biopsies: the concordance of radiology and histopathology findings must be ensured. No data is available to recommend surgery; in case of non-in sano resection for ADH, FEA, ALH, LCIS (except pleomorphic type), RS, MLL: surgery does not seem to be necessary; in case of previous ADH, ALH, LCIS: a specific follow-up is recommended in accordance with HAS's recommendations. In case of FEA and RS or MLL combined with atypia, little data are yet available to differ the management from others lesions with atypia; in case of UDH, usual sclerosing adenosis, RS without atypia, fibro cystic disease: no specific follow up is recommended in agreement with HAS's recommendations. PMID- 26545857 TI - Neuroepidemiology of Porencephaly, Schizencephaly, and Hydranencephaly in Miyagi Prefecture, Japan. AB - BACKGROUND: No population-based surveys of porencephaly, schizencephaly, and hydranencephaly have been conducted in Japan or other Asian countries. We performed a neuroepidemiologic analysis to elucidate the incidence of porencephaly, schizencephaly, and hydranencephaly in Miyagi prefecture, Japan, during 2007-2011. METHODS: We sent inquiry forms in February 2012 to three neonatal intensive care units, 25 divisions of orthopedic surgery in municipal hospitals, 33 divisions of pediatrics including one university hospital, municipal hospitals, pediatric practitioners, and institutions for physically handicapped children located in Miyagi prefecture. These covered all clinics related to pediatric neurology and orthopedic surgery in Miyagi prefecture. In the inquiry, diagnostic criteria for porencephaly, schizencephaly, and hydranencephaly were described and representative images of magnetic resonance imaging were shown. We obtained an 82% (27 of 33) response rate from the divisions of pediatrics, a 100% (3 of 3) response rate from the neonatal intensive care units, and a 68% (17 of 25) response rate from orthopedic surgery clinics. The magnetic resonance imaging scans of each patient were retrieved and inspected. RESULTS: Five, one, and two individuals developed porencephaly, schizencephaly, and hydranencephaly, respectively. The estimated incidence rates of porencephaly, schizencephaly, and hydranencephaly were 5.2 (95% confidence interval [CI], 0.6-9.8), 1.0 (95% CI, 0.0-3.1), and 2.1 (95% CI, 0.0-5.0) per 100,000 live births, respectively. CONCLUSIONS: The prevalence rates of porencephaly, schizencephaly, and hydranencephaly at birth reported herein are compatible with results reported previously in the United States and European countries. The overall prevalence rate of these three diseases was 8.3 (95% CI, 2.6-14.1) per 100,000 live births. PMID- 26545858 TI - Orbital Infection With Intracranial Involvement. PMID- 26545859 TI - The results of a survey highlighting issues with feedback on medical training in the United Kingdom and how a Smartphone App could provide a solution. AB - BACKGROUND: Feedback drives learning in medical education. Healthcare Supervision Logbook (HSL) is a Smartphone App developed at Sheffield Teaching Hospitals for providing feedback on medical training, from both a trainee's and a supervisor's perspective. In order to establish a mandate for the role of HSL in clinical practice, a large survey was carried out. METHODS: Two surveys (one for doctors undertaking specialty training and a second for consultants supervising their training) were designed. The survey for doctors-in-training was distributed to all specialty trainees in the South and West localities of the Health Education Yorkshire and the Humber UK region. The survey for supervisors was distributed to all consultants involved in educational and clinical supervision of specialty trainees at Sheffield Teaching Hospitals. RESULTS: The results confirm that specialty trainees provide feedback on their training infrequently-66 % do so only annually. 96 % of the specialty trainees owned a Smartphone and 45 % said that they would be willing to use a Smartphone App to provide daily feedback on the clinical and educational supervision they receive. Consultant supervisors do not receive regular feedback on the educational and clinical supervision they provide to trainees-56 % said they never received such feedback and 33 % said it was only on an annual basis. 86 % of consultants surveyed owned a Smartphone and 41 % said they would be willing to use a Smartphone App to provide feedback on the performance of trainees they were supervising. CONCLUSIONS: Feedback on medical training is recorded by specialty trainees infrequently and consultants providing educational and clinical supervision often do not receive any feedback on their performance in this area. HSL is a simple, quick and efficient way to collect and collate feedback on medical training to improve this situation. Good support and education needs to be provided when implementing this new technology. PMID- 26545862 TI - In vitro study of the antibacterial properties and impact strength of dental acrylic resins modified with a nanomaterial. AB - STATEMENT OF PROBLEM: The accumulation of bacteria on the surface of dental prostheses can lead to systemic disease. PURPOSE: The purpose of this in vitro study was to evaluate the growth of Staphylococcus aureus and Pseudomonas aeruginosa on the surface of autopolymerizing (AP) and heat-polymerizing (HP) acrylic resins incorporated with nanostructured silver vanadate (beta-AgVO3) and its impact strength. MATERIAL AND METHODS: For each resin, 216 circular specimens (9 * 2 mm) were prepared for microbiologic analysis and 60 rectangular specimens (65 * 10 * 3.3 mm) for mechanical analysis, according to the percentage of beta AgVO3: 0%, control group; 0.5%; 1%; 2.5%; 5%; and 10%. After a biofilm had formed, the metabolic activity of the bacteria was measured using the XTT reduction assay (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5 carboxanilide) (n=8), and the number of viable cells was determined by counting colony forming units per milliliter (CFU/mL) (n=8). Confocal laser scanning microscopy (CLSM) was used to complement the analyses (n=2). The mechanical behavior was evaluated by impact strength assays (n=10). Data were analyzed by 2 way ANOVA, followed by the Tukey honestly significant difference (HSD) post hoc test (alpha=.05). RESULTS: The addition of 5% and 10% beta-AgVO3 significantly decreased the metabolic activity of P. aeruginosa for both resins (P<.05). The HP resin promoted a greater reduction in metabolic activity than the AP resin (P<.05). No difference was found in the metabolic activity of S. aureus according to the XTT (P>.05). The number of CFU/mL for S. aureus and P. aeruginosa decreased significantly when 5% and 10% beta-AgVO3 were added (P<.001). These concentrations significantly reduced the impact strength of the resins (P<.001) because the system was weakened by the presence of clusters of beta-AgVO3. CONCLUSION: The addition of beta-AgVO3 can provide acrylic resins with antibacterial activity but reduces their impact strength. More efficient addition methods should be investigated. PMID- 26545863 TI - Material compatibility and antimicrobial activity of consumer products commonly used to clean dentures. AB - STATEMENT OF PROBLEM: Regular denture cleaning is essential to good oral health, but only limited evidence is available regarding the effects of common cleaning routines. PURPOSE: The purpose of this in vitro study was to determine the compatibility of denture materials with and the antimicrobial effects of typical cleaning regimens. MATERIAL AND METHODS: The evaluated treatments were derived from a study of dental professional recommendations and consumer habits, including denture cleanser tablets, toothpaste, mouthwash, isopropyl alcohol (IPA), household bleach, soap, and vinegar. The material integrity of denture materials, including polymethyl methacrylate (PMMA) and metals, was evaluated by scanning electron microscopy and profilometry after treatment with laboratory regimens simulating 2 years of typical consumer use. Treatments were also evaluated in a microbial kill time assay against a range of oral microorganisms with typical treatment regimens. RESULTS: Alcohol-based mouthwash and IPA damaged the surface of PMMA, and brushing with toothpaste caused scratching and surface material loss. Bleach caused limited damage to PMMA, but corroded CoCr alloy (pitting) and solder (layer formation). Denture tablets caused little damage to any materials apart from the layer formation on silver solder. Vinegar and soap were compatible with all materials. In antimicrobial assays, bleach gave excellent results, and IPA and mouthwash required concentrated dilutions to be effective. Cleanser tablets were effective at 5 minutes treatment time against all organisms. Toothpaste was effective against bacteria but not Candida albicans. Vinegar, soaps, salt, and sodium bicarbonate were microbially ineffective. CONCLUSIONS: Bleach was highly antimicrobial but incompatible with metal dental prosthesis components. IPA and mouthwash were antimicrobial but damaged PMMA. Specialist denture cleanser tablets gave a good combination of microbial efficacy and reasonable material compatibility. PMID- 26545860 TI - Bronchiectasis diagnosed after renal transplantation: a retrospective multicenter study. AB - BACKGROUND: Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation. METHODS: We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected. RESULTS: Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 +/- 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis. CONCLUSIONS: These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting. PMID- 26545861 TI - Argonaute 2 and nasopharyngeal carcinoma: a genetic association study and functional analysis. AB - BACKGROUND: Argonaute 2 (AGO2), a central component of RNA-induced silencing complex, plays critical roles in cancer. We examined whether the single nucleotide polymorphisms (SNPs) of AGO2 were related to the risk of nasopharyngeal carcinoma (NPC). METHODS: Twenty-five tag SNPs within AGO2 were genotyped in Guangxi population consisting of 855 NPC patients and 1036 controls. The SNPs significantly associated with NPC were further replicated in Guangdong population consisting of 996 NPC patients and 972 controls. Functional experiments were conducted to examine the biologic roles of AGO2 in NPC. RESULTS: A significantly increased risk of advanced lymph node metastasis of NPC was identified for the AGO2 rs3928672 GA + AA genotype compared with GG genotype in both the Guangxi and Guangdong populations (combined odd ratio = 2.08, 95 % confidence interval = 1.44-3.01, P = 8.60 * 10(-5)). Moreover, the AGO2 protein expression levels of rs3928672 GA + AA genotype carriers were higher than the GG genotype carriers in the NPC tissues (P = 0.041), and AGO2 was significantly over expressed in NPC tissues compared with non-cancerous nasopharyngeal tissues (P = 0.011). In addition, AGO2 knockdown reduced cell proliferation, induced apoptosis, and inhibited migration of NPC cells. Furthermore, gene expression microarray showed that genes altered following AGO2 knockdown were clustered in tumorigenesis and metastasis relevant pathways. CONCLUSIONS: Our findings suggest that the genetic polymorphism in AGO2 may be a risk factor for the advanced lymph node metastasis of NPC in Chinese populations, and AGO2 acts as an oncogene in the development of NPC. PMID- 26545864 TI - Risk factors associated with early implant failure: A 5-year retrospective clinical study. AB - STATEMENT OF PROBLEM: The replacement of lost teeth with dental implants is a widespread treatment whose associated problems are also frequently encountered. Nevertheless, the factors associated with early implant failure have not been well documented. Further analyses of the factors influencing osseointegration establishment are required to maximize the predictability of the procedure and minimize implant failures. PURPOSE: The purpose of this retrospective clinical study was to explore the association between possible risk factors and early implant failure. MATERIAL AND METHODS: This retrospective clinical study evaluated 142 participants who received 276 external connection BTI implants between 2007 and 2011. Participant variables (age, sex, systemic disease, tobacco use, alcohol consumption, bruxism, and degree of periodontal disease), implant variables (type of edentulism, localization, area, diameter, length, and bone quality), intervention variables (expansion mechanisms, sinus augmentation techniques, bone regeneration, and implant insertion), and postoperative variables (presence of pain/inflammation at 1 week postsurgery) were studied. A multilevel logistic regression model (mixed effects-type model) was used to determine the influence of variables on early implant failure. RESULTS: Early implant failure was significantly associated with the male sex (P=.001), severe periodontal disease (P=.005), short implants (P=.001), expansion technique (P=.002), and postoperative pain/inflammation at 1 week postsurgery (P<.001). CONCLUSIONS: Early dental implant failure is more frequent in men and in individuals with severe periodontal disease, short implants, pain/inflammation at 1 week postsurgery, or bone expansion treatment. PMID- 26545865 TI - Aging Successfully: The Key to Aging in Place. PMID- 26545866 TI - Up-regulation of CYLD enhances Listeria monocytogenes induced apoptosis in THP-1 cells. AB - Listeria monocytogenes (Lm), a facultative anaerobic gram-positive bacterium, causes listeriosis. Immune cell apoptosis is considered to be one pathogenic factor for listeriosis. As a deubiquitinase, CYLD is an important regulator both in innate immune response and apoptosis by negatively modulating NF-kappaB pathway. However the role of CYLD in Lm induced apoptosis remains unclear. Here we found that CYLD is significantly up-regulated in macrophages upon its infection. There is a moderate decrease in Lm proliferation and apoptotic cells in siRNA-induced CYLD knockdown THP-1 cells. Thereby CYLD may be involved in cell apoptosis mediated by Lm infection and its proliferation. PMID- 26545867 TI - Surgical resection of unilateral thalamic tumors in adults: approaches and outcomes. AB - BACKGROUND: The thalamic tumors were less common in adults and this study aimed to determine the clinical features, surgical approaches, and outcomes of adult thalamic tumors, which have not been well-described in the literature. METHODS: We reviewed the clinical presentation, surgical approach, perioperative mortality and morbidity, and outcomes of 111 operated patients (71 males, 40 females; mean age at presentation, 33.4 +/- 13.2 years) with unilateral thalamic tumor. RESULTS: The most common clinical presentations were increased intracranial pressure (65%) and motor deficits (40%). Five surgical approaches were used depending on tumor location; the most common was the transparieto-occipital approach (47.7%). According to peri- and post-operative magnetic resonance imaging findings, the tumors were totally resected in 29 cases (26.1%), subtotally resected in 54 cases (48.6%), and partially resected in 21 cases (18.9%). Five patients died during the perioperative period (4.5%, 5/111). The most common morbidity was motor deficits (21.7%, 23/106). According to histological findings, there were 50 high-grade and 61 low-grade tumors. Median survival of patients with low- and high-grade tumors were 40 and 12 months, respectively (mean follow-up, 37.3 months). Survival was significantly longer in cases of total or subtotal resection (median, 28 months) compared to partial resection or biopsy (median, 12 months). Survival was poorer in adults than in previous reported pediatrics. CONCLUSIONS: Surgical treatment of adult thalamic tumors must be individualized according to tumor location. Low-grade tumors and total/subtotal resection seem to be predictors of better surgical outcomes. Nevertheless, the outcome of adult patients were still worse than pediatric patients. PMID- 26545868 TI - Willis-Ekbom disease is not associated with poor cardiovascular health in adults. AB - BACKGROUND: Willis-Ekbom disease (WED), also called restless legs syndrome (RLS), is a neurologic sensorimotor disease that may be associated with cardiovascular disease. Given high morbidity and mortality rates of cardiovascular disease worldwide, we assessed the relation between WED/RLS and cardiovascular health risks in a native South American population. We prospectively analyzed data from The Atahualpa Project of Ecuadorian adults aged 40 years and older. Physicians interviewed consented persons on the health behavior and health factors of the American Heart Association (AHA) for ideal cardiovascular health in adults and underwent fasting laboratory blood collection and blood pressure evaluation. Certified neurologists conducted face-to-face interviews using the International Restless Legs Syndrome Study Group (IRLSSG) field instrument. Persons testing positive for WED/RLS and age-and sex-matched controls underwent confirmatory physical examinations conducted by a neurologist and a sleep specialist to whom IRLSSG designation was blinded. FINDINGS: Of 665 persons, 94 (14 %) tested positive in IRLSSG; 40 (6 %) had a diagnosis of WED/RLS after neurologic examination and interview. Patients with WED/RLS were younger (53.5 vs 59.9 years, P = .001), without significant differences in sex ratios. Among AHA risk factors, only obesity was significantly more prevalent among patients with WED/RLS (42.5 % vs 23.5 %, P = .01). However, after adjustment for confounders, body mass index was not significantly associated with WED/RLS. CONCLUSIONS: In adult Amerindians, although obesity and body mass index were associated with WED/RLS on univariate analyses, the association was not present after adjustment for confounders. No other significant associations were found between WED/RLS and AHA cardiovascular metrics. PMID- 26545869 TI - A picture of trends in Aujeszky's disease virus exposure in wild boar in the Swiss and European contexts. AB - BACKGROUND: In parallel to the increase of wild boar abundance in the past decades, an increase of exposure to the Aujeszky's disease virus (ADV) has been reported in wild boar in several parts of Europe. Since high animal densities have been proposed to be one of the major factors influencing ADV seroprevalence in wild boar populations and wild boar abundance has increased in Switzerland, too, a re-evaluation of the ADV status was required in wild boar in Switzerland. We tested wild boar sera collected from 2008-2013 with a commercial ELISA for antibodies against ADV. To set our data in the European context, we reviewed scientific publications on ADV serosurveys in Europe for two time periods (1995 2007 and 2008-2014). RESULTS: Seven out of 1,228 wild boar sera were positive for antibodies against ADV, resulting in an estimated seroprevalence of 0.57% (95% confidence interval CI: 0.32-0.96%). This is significantly lower than the prevalence of a previous survey in 2004-2005. The literature review revealed that high to very high ADV seroprevalences are reported from Mediterranean and Central eastern countries. By contrast, an "island" of low to medium seroprevalences is observed in the centre of Europe with few isolated foci of high seroprevalences. We were unable to identify a general temporal trend of ADV seroprevalence at European scale. CONCLUSIONS: The seroprevalence of ADV in wild boar in Switzerland belongs among the lowest documented in Europe. Considering the disparity of seroprevalences in wild boar in Europe, the fact that seroprevalences in Switzerland and other countries have decreased despite increasing wild boar densities and the knowledge that stress leads to the reactivation of latent ADV with subsequent excretion and transmission, we hypothesize that not only animal density but a range of factors leading to stress - such as management - might play a crucial role in the dynamics of ADV infections. PMID- 26545870 TI - Retrospective evaluation of prehospital triage, presentation, interventions and outcome in paediatric drowning managed by a physician staffed helicopter emergency medical service. AB - BACKGROUND: Drowning patients may benefit from the advanced airway management capabilities that can be provided by physician staffed helicopter emergency medical services. The aim of this study is to describe paediatric drowning patients treated by such a service examining tasking systems, initial physiology at the incident scene, survival and neurological outcome. METHODS: Retrospective analysis of paediatric drowning victims over a 5- year period. Case identification system, patient age, site of drowning, presence or absence of cardiac output, first Glasgow Coma Scale (GCS) score and interventions were collected from prehospital notes, and survival and neurological outcomes from hospital and rehabilitation notes. RESULTS: The P-HEMS direct case identification system operating in parallel with a central control system identified all severe drowning cases but 3 of 7 cases (43%) were missed when the central control system operated in isolation. All severe drowning cases (22) identified for P-HEMS response were intubated and transported directly to a paediatric specialist centre. Intubation required adjuvant anaesthesia in 10 (45%) cases. All children with GCS greater than eight on arrival of the P-HEMS survived neurologically intact. Seven of eight children with a GCS between four and seven survived without neurological impairment and all children with a GCS greater than three survived. Four of twelve asystolic children survived including one child who at 18 months post drowning is neurologically normal. All children who survived had return of spontaneous circulation prior to arrival in the emergency department. CONCLUSIONS: P-HEMS played a significant role in the management of severe paediatric drowning in this case series. Requirement for P-HEMS only interventions were high and all identified cases were transferred directly to a paediatric specialist centre. Discontinuation of the P-HEMS direct case identication system that operated during the majority of the study period resulted in deterioration in system performance with some paediatric drowning cases subsequently not identified for P-HEMS response being transported to adult hospitals. PMID- 26545871 TI - Toxicity profile and early clinical outcome for advanced head and neck cancer patients treated with simultaneous integrated boost and volumetric modulated arc therapy. AB - BACKGROUND: Shortening the overall treatment time without increasing acute reactions is one of the major aims in radiotherapy for head and neck cancer (HNC). Volumetric modulated arc therapy (VMAT) with Simultaneous Integrated Boost (SIB) showed improvements in outcome and pattern of toxicity. Patients with stage III-IV HNC treated with VMAT-SIB have been analysed, and doses were correlated to limiting structures and toxicity. METHODS: One hundred two patients treated from December 2008 to August 2014 were analysed. Patients were treated with VMAT (RapidArc) and SIB in 33 fractions for a total dose of 69.96 and 54.45Gy, respectively. For organs at risk, D1/3 V, D1/2 V, D2/3 V, the mean dose, VD with D = 10,20,30,40,50,70 Gy were analysed. For targets, D98%, D2%, and V95%, V107%, conformity and homogeneity indexes were calculated. Toxicity was graded according to CTCAE3. RESULTS: Oral cavity V30Gy, V40Gy, and V70Gy, were found correlated with mucosal toxicity grading. Concerning salivary glands, significant was only D2/3V for one of the two parotids. Almost all analysed parameters of the inferior constrictor muscle were significant while no correlations were found for middle and superior constrictors. With median follow-up of 19 months, Overall Survival (OS) at 3 and 5 years was 83 % +/- 4 % and 73 % +/- 10 %. Mean OS was 51 +/- 3 months. Disease Free Survival (DFS) at 3 and 5 years was 71 % +/- 7 %, and 34 % +/- 16 %. Mean DFS was 43 +/- 3 months. CONCLUSIONS: RapidArc technology and SIB with 1.65 and 2.12Gy/fraction for 33 fractions showed a good toxicity profile and encouraging trend for OS and DFS for patients with stage III-IV HNC. PMID- 26545872 TI - Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive chronic interstitial lung disease with poor survival. Previous reports suggested the contributory effect of receptor for advanced glycation end products (RAGE) to the pathogenesis of IPF. But the findings are controversial. The present in vivo study with RAGE null mice, we further confirmed the evidence that lack of RAGE evolves worse bleomycin induced pulmonary fibrosis compared with control mice. Moreover, RAGE null mice spontaneously developed similar pathogenesis of lung fibrosis via immunohistochemical staining. In addition, we investigated the negative roles of RAGE on epithelial-mesenchymal transition (EMT) indicated by elevated alpha smooth muscle actin (alpha-SMA) and collagen-I (Col-I) deposition in A549 cell treated with transforming growth factor-beta (TGF-beta), all of which were blocked by sRAGE, a decoy receptor. Furthermore, interacting with the specific ligand as AGE, RAGE blocked TGF-beta-induced activation of Smad2, ERK and JNK signals in A549 cells, which were also challenged by sRAGE administration. This present study confirmed an important role of RAGE in vivo and vitro models of pulmonary fibrosis and suggested the therapeutic possibility for pulmonary fibrosis via RAGE regulation. PMID- 26545873 TI - Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers. AB - Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 h (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 h post LPS challenge. While the cytokine response was more pronounced at 6 h, the influx of neutrophils and monocytes dominated at 24 h; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 h after the two separate challenges. The within subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 h and cytokine variables at 6 h. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine). PMID- 26545874 TI - Cough in interstitial lung disease. AB - Cough in the context of interstitial lung disease (ILD) has not been the focus of many studies. However, chronic cough has a major impact on quality of life in a significant proportion of patients with ILD. For the purpose of this review, we have chosen to highlight some of the more frequently encountered diffuse lung diseases including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and systemic sclerosis associated ILD. Many of the underlying mechanisms remain speculative and further research is now required to elucidate the complex pathways involved in the pathogenesis of chronic cough in ILD. This will hopefully pave the way for the identification of new therapeutic agents to alleviate this distressing and often intractable symptom. PMID- 26545875 TI - Characterization of the murine macrophage response to infection with virulent and avirulent Burkholderia species. AB - BACKGROUND: Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered. RESULTS: The goal of this study is to profile murine macrophage mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt. CONCLUSIONS: These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host Burkholderia interactions. PMID- 26545876 TI - Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith-Wiedemann syndrome. AB - BACKGROUND: Congenital hyperinsulinism (HI) can have monogenic or syndromic causes. Although HI has long been recognised to be common in children with Beckwith-Wiedemann syndrome (BWS), the underlying mechanism is not known. METHODS: We characterised the clinical features of children with both HI and BWS/11p overgrowth spectrum, evaluated the contribution of KATP channel mutations to the molecular pathogenesis of their HI and assessed molecular pathogenesis associated with features of BWS. RESULTS: We identified 28 children with HI and BWS/11p overgrowth from 1997 to 2014. Mosaic paternal uniparental isodisomy for chromosome 11p (pUPD11p) was noted in 26/28 cases. Most were refractory to diazoxide treatment and half required subtotal pancreatectomies. Patients displayed a wide range of clinical features from classical BWS to only mild hemihypertrophy (11p overgrowth spectrum). Four of the cases had a paternally transmitted KATP mutation and had a much more severe HI course than patients with pUPD11p alone. CONCLUSIONS: We found that patients with pUPD11p-associated HI have a persistent and severe HI phenotype compared with transient hypoglycaemia of BWS/11p overgrowth patients caused by other aetiologies. Testing for pUPD11p should be considered in all patients with persistent congenital HI, especially for those without an identified HI gene mutation. PMID- 26545877 TI - UNC80 mutation causes a syndrome of hypotonia, severe intellectual disability, dyskinesia and dysmorphism, similar to that caused by mutations in its interacting cation channel NALCN. AB - BACKGROUND: A syndrome of profound hypotonia, intellectual disability, intrauterine growth retardation with subsequent failure to thrive, dyskinesia and epilepsy was diagnosed in Bedouin Israeli families. Mild dysmorphism was evident: plagiocephaly, broad forehead with prominent nose, smooth philtrum and congenital esotropia. We set out to decipher the molecular basis of this syndrome. METHODS: Genome-wide linkage analysis and fine mapping were done. Whole exome sequencing data were filtered for candidate variants within locus. Validation and segregation of the mutation was assayed via Sanger sequencing. UNC80 expression pattern was analysed through reverse transcription PCR. RESULTS: Homozygosity mapping followed by fine mapping identified a 7.5 Mb disease-associated locus (logarithm of odds score 3.5) on chromosome 2. Whole exome and Sanger sequencing identified a single homozygous nonsense mutation within this locus, segregating within the families as expected for recessive heredity and not found in a homozygous state in 150 Bedouin controls: c.151C>T, p.(R51*) in UNC80. CONCLUSIONS: The syndrome described is caused by a mutation in UNC80, truncating most of the 3258 amino acids highly conserved encoded protein, that has no known motifs. UNC80 bridges between UNC79 and the cation channel NALCN, enabling NALCN's role in basal Na(+) leak conductance in neurons, essential for neuronal function. The phenotype caused by the UNC80 mutation resembles that previously described for homozygous NALCN mutations. PMID- 26545878 TI - Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene. AB - BACKGROUND: Leukodystrophies are genetic white matter disorders affecting the formation or maintenance of myelin. Among the recently discovered genetic defects associated with leukodystrophies, several genes converge on a common mechanism involving protein transcription/translation and ER stress response. METHODS: The genetic basis of a novel congenital leukodystrophy, associated with early onset spastic paraparesis, acquired microcephaly and optic atrophy was studied in six patients from three unrelated Ashkenazi-Jewish families. To this end we used homozygosity mapping, exome analysis, western blot (Hikeshi, HSF1-pS326 and b actin) in patient fibroblasts, indirect immunofluorescence (HSP70 and HSF1) in patient fibroblasts undergoing heat shock stress, nuclear injection of plasmids expressing Hikeshi or EGFP in patient fibroblasts, in situ hybridization and Immunoblot analysis of Hikeshi in newborn and adult mouse brain. RESULTS: All the patients were homozygous for a missense mutation, p.Val54Leu, in C11ORF73 encoding HSP70 nuclear transporter protein, Hikeshi. The mutation segregated with the disease in the families and was carried by 1:200 Ashkenazi-Jewish individuals. The mutation was associated with undetectable level of Hikeshi in the patients' fibroblasts and with lack of nuclear HSP70 during heat shock stress, a phenomenon which was reversed upon the introduction of normal human Hikeshi to the patients cells. Hikeshi was found to be expressed in central white matter of mouse brain. CONCLUSIONS: These data underscore the importance of Hikeshi for HSP70 relocation into the nucleus. It is likely that in the absence of Hikeshi, HSP70 cannot attenuate the multiple heat shock induced nuclear phenotypes, leaving the cells unprotected during heat shock stress. We speculate that the sudden death of three of the six patients following a short febrile illness and the life-threatening myo-pericarditis in the fourth are the result of excess extra-nuclear HSP70 level which initiates cytokine release or provide target for natural killer cells. Alternatively, nuclear HSP70 might play an active role in stressed cells protection. PMID- 26545879 TI - Enhancement by Uridine Diphosphate of Macrophage Inflammatory Protein-1 Alpha Production in Microglia Derived from Sandhoff Disease Model Mice. AB - Sandhoff disease (SD) is a lysosomal beta-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including GM2 ganglioside, and progressive neurodegeneration. Macrophage inflammatory protein 1alpha (MIP-1alpha) is a crucial factor for microglia-mediated neuroinflammation in the onset or progression of SD. However, the transmitter-mediated production of MIP-1alpha in SD is still poorly understood.Extracellular nucleotides, including uridine diphosphate (UDP), leaked by either injured or damaged neuronal cells activate microglia to trigger chemotaxis, phagocytosis, macropinocytosis, and cytokine production.In this study, we demonstrated that UDP enhanced the production of MIP-1alpha by microglia derived from SD mice (SD-Mg), but not that from wild-type mice (WT-Mg). The UDP-induced MIP-1alpha production was mediated by the activation of P2Y6 receptor, ERK, and JNK. We also found the amount of dimeric P2Y6 receptor protein to have increased in SD-Mg in comparison to WT-Mg. In addition, we demonstrated that the disruption of lipid rafts enhanced the effect of UDP on MIP-1alpha production and the disordered maintenance of the lipid rafts in SD-Mg. Thus, the accumulation of undegraded substrates might cause the enhanced effect of UDP in SD-Mg through the increased expression of the dimeric P2Y6 receptors and the disordered maintenance of the lipid rafts. These findings provide new insights into the pathogenic mechanism and therapeutic strategies for SD. PMID- 26545880 TI - Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency. AB - BACKGROUND: Reports on cognitive outcomes in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are scarce. We present results from neuropsychological assessments of eight patients diagnosed with LCHADD prior to newborn screening with regard to clinical disease severity. METHODS: Intellectual ability and adaptive and executive functions were assessed using age-appropriate Wechsler Scales, Adaptive Behavior Assessment Scales (ABAS), and Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Five patients performed in the normal range on IQ tests but with lower scores on verbal working memory. In addition, they had lower parent-rated adaptive and executive functions.Three patients had intellectual disabilities with IQs below normal and/or autism spectrum disorders. In addition, they had low results on parent-rated adaptive functions. (Two of these patients had epilepsy.) Conclusions: Patients with LCHADD seem to have a specific cognitive pattern, with presentation as intellectual disability and specific autistic deficiencies or a normal IQ with weaknesses in auditive verbal memory and adaptive and executive functions. Future studies are warranted to investigate whether newborn screening programs and early treatment may promote improved neuropsychological development and outcomes. PMID- 26545881 TI - Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer. AB - BACKGROUND: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries, and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin. Although No. 8a are considered to have lymphatic flow from the r-GA basin, there might be additional multiple lymphatic flows into No. 8a. The aim of this study is to analyze the lymphatic flows to No. 8a and to investigate the clinical significance of No. 8a as a sentinel node (SN No. 8a). METHODS: Four hundred and twenty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. RESULTS: We detected SN No. 8a in 35 (8.2 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the left gastric artery (l-GA) basin (66 %), right gastroepiploic artery (r-GEA) basin (54 %), and right gastric artery (r-GA) basin (46 %). In addition, celiac artery lymph nodes were detected as SNs significantly more frequently. Function-preserving surgery was performed significantly less often in patients with SN No. 8a (p =0.018). CONCLUSIONS: We found that SN No. 8a seemed to have lymphatic flow not only from the r-GA basin, but also from the l GA basin or r-GEA basin. When SN No. 8a are detected, we should be careful to perform function-preserving surgery, even in SN-negative cases. PMID- 26545884 TI - Whole-body MRI in generalized cystic lymphangiomatosis in the pediatric population: diagnosis, differential diagnoses, and follow-up. AB - OBJECTIVE: Generalized cystic lymphangiomatosis is a particularly rare disease with variable involvement of skeletal and extraskeletal sites. The key role of imaging in the diagnosis of this disease is no longer in doubt. The aim of our study was to demonstrate the contribution of whole-body magnetic resonance imaging (WB-MRI) at the diagnostic stage and during the follow-up in the pediatric population. SUBJECTS AND METHODS: Three children were included from 2008. The inclusion criteria were radiological images (conventional radiographs, computed tomography, and MRI) compatible with histological confirmation. Each child included received WB-MRI at the diagnosis stage and during follow-up. RESULTS: WB-MRI detected multiple hypointense T1 and hyperintense T2-STIR cystic bony lesions. One unnoticed mass in the retroperitoneum on computed tomography was easily detected by MRI. Mediastinal involvement was observed in one asymptomatic case. Histology was contributory in all cases. Preventive intramedullary nailings was done in one case. Follow-up WB-MRI detected new asymptomatic lesions in all cases. One child presented a third episode of lymphangitis of the right thigh during follow-up. CONCLUSIONS: Due to its high sensitivity to diagnose, ability to eliminate differential diagnoses and make exhaustive lesions assessment, and its non-radiating character for long-term follow-up, WB-MRI is highly recommended for generalized cystic lymphangiomatosis in the pediatric population. PMID- 26545885 TI - Alleviating effects of exogenous NO on tomato seedlings under combined Cu and Cd stress. AB - To investigate the effect of NO on the different origin and regulation of oxidative stress of Cu and/or Cd, tomato seedlings were treated with Cu, Cd, or Cu + Cd in a nutrient solution culture system. The main effect of Cu(2+) was a significant reduction in root activity and nitrate reductase (NR) activity, which was similar to that under 50 MUM Cd treatment, but promoted Cu accumulation. The supply of Cu under Cd treatment decreased Cd concentration, while not altered Cu concentration by contrast with Cu treatment, which is suggestive of a replacement of Cu(2+) with Cd(2+) and effective decrease in the boiotoxicity of 50 MUM Cd(2+) to tomato seedlings. However, NO alleviated the restriction to NR activity significantly and made the biomass of tomato seedlings recover under Cd treatment, and also increased root activity under Cu and Cu + Cd treatment. Exogenous NO markedly reduced the absorption and transportation of Cu but did not obviously change the translocation of Cd to the aboveground parts under Cu + Cd treatment. Both metals induced lipid peroxidation via the decreasing activation of antioxidant enzymes. The antioxidant enzyme system worked differently under Cu, Cd, or Cu + Cd stress. The activities of peroxidase (POD) and catalase (CAT) were higher under single Cd stress than under the control. Meanwhile, Cu + Cd treatment decreased the activities of POD, superoxide dismutase (SOD), and ascorbic acid peroxidase (APX). Exogenous NO increased POD and SOD activities in the leaves and roots, and CAT activity in the roots under combined Cu and Cd stress. These results suggest that a different response and regulation mechanism that involves exogenous NO is present in tomato seedlings under Cu and Cd stress. PMID- 26545886 TI - PCDDs, PCDFs, and PCBs co-occurrence in TiO2 nanoparticles. AB - In the present study, we report on the co-occurrence of persistent organic pollutants (POPs) adsorbed on nanoparticular titanium dioxide (TiO2). We report on the finding of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) on the surface of commercially available TiO2 nanoparticles, being formed during the fabrication process of the TiO2. Thereby, the samples comprise PCBs with higher congener numbers or, in the absence of PCBs, a high concentration of PCDDs and PCDFs. This new class of POPs on an active catalytic surface and the great range of applications of nanoparticular TiO2, such as in color pigments, cosmetics, and inks, give rise to great concern due to their potential toxicity. PMID- 26545887 TI - Surface capping and size-dependent toxicity of gold nanoparticles on different trophic levels. AB - In the present study, the toxicity of gold nanoparticles (Au NPs) was evaluated on various trophic organisms. Bacteria, algae, cell line, and mice were used as models representing different trophic levels. Two different sizes (CIT30 and CIT40) and surface-capped (CIT30-polyvinyl pyrrolidone (PVP)-capped) Au NPs were selected. CIT30 Au NP aggregated more rapidly than CIT40 Au NP, while an additional capping of PVP (CIT30-PVP capped Au NP) was found to enhance its stability in sterile lake water medium. Interestingly, all the forms of NPs evaluated were stable in the cell culture medium during the exposure period. Size and dose-dependent cytotoxicities were observed in both bacteria and algae, with a strong dependence on reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. CIT30-PVP capped Au NP showed a significant decrease in toxicity compared to CIT30 Au NP in bacteria and algae. In the SiHa cell line, dose- and exposure-dependent decline in cell viability were noted for all three types of Au NPs. In mice, the induction of DNA damage was size and dose dependent, and surface functionalization with PVP reduced the toxic effects of CIT30 Au NP. The exposure to CIT30, CIT40, and CIT30-PVP capped Au NPs caused an alteration of the oxidative stress-related endpoints in mice hepatocytes. The toxic effects of the gold nanoparticles were found to vary in diverse test systems, accentuating the importance of size and surface functionalization at different trophic levels. PMID- 26545888 TI - Histopathological and genotoxic effects of chlorpyrifos in rats. AB - This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo. PMID- 26545889 TI - Effect of tourmaline on denitrification characteristics of hydrogenotrophic bacteria. AB - To improve the denitrification characteristics of anaerobic denitrifying bacteria and obviate the disadvantage of use of explosive hydrogen gas, tourmaline, a polar mineral, was added to the hydrogenotrophic denitrification system in this study. Microbial reduction of nitrate in the presence of tourmaline was evaluated to assess the promotion effect of tourmaline on nitrate biodegradation. The experiment results demonstrated that tourmaline speeded up the cultivation process of bacteria from 65 to 36 days. After domestication of the bacteria, nitrate (50 mg NO3 (-)-N L(-1)) was completely removed within 3 days in the combined tourmaline-bacteria system, and the generated nitrite was also removed within 8 days. The reduction rate in this system is higher relative to that in the bacteria system alone. Efficient removal of nitrate by tourmaline-supported anaerobic bacteria (without external hydrogen input) indicated that tourmaline might act as the sole hydrogen donor to sustain autotrophic denitrification. Besides the production of hydrogen, the promoted activity of anaerobic denitrifying bacteria might be caused by the change of water properties, e.g., the pH of aqueous solutions was altered to about 8.0 and the oxidation-reduction potential decreased by 62 % in the tourmaline system. The distinctive effects of tourmaline on bacteria were related to its electric properties. PMID- 26545890 TI - Study of the degradation of butyltin compounds in surface water samples under different storage conditions using multiple isotope tracers and GC-MS/MS. AB - The degradation of butyltin compounds in surface water samples under different storage conditions has been studied. A triple spike solution, containing monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) labelled with a different tin isotope, was added to the sample to calculate the extent of the interconversion reactions among butyltin compounds. Real surface water samples (river water) were collected and stored in glass, polypropylene or polytetrafluoroethylene (PTFE) containers. The presence of light, addition of acetic acid, storage temperature (22, 4 or -18 degrees C), and the influence of a filtration step were evaluated. Moreover, Milli-Q water with and without the addition of a high concentration of humic acids was prepared in parallel and the results compared to those obtained from the real samples. The water samples were analysed by gas chromatography-tandem mass spectrometry (GC-MS/MS) in selected reaction monitoring (SRM) mode at two different storage times (2 weeks and 4 months after its preparation) to carry out both a short- and a long-term stability study. The lowest butyltin degradation was obtained when the samples were stored at -18 degrees C in the dark. Under these conditions, both TBT and DBT showed negligible dealkylation factors after 2 weeks. After 4 months, DBT dealkylation to MBT increased up to 19 % but TBT degradation was not observed. PMID- 26545891 TI - Effectiveness of rabbit manure biofertilizer in barley crop yield. AB - The quality of biofertilizers is usually assessed only in terms of the amount of nutrients that they supply to the crops and their lack of viable pathogens and phytotoxicity. The goal of this study was to determine the effectiveness of a liquid biofertilizer obtained from rabbit manure in terms of presence of pathogens, phytotoxicity, and its effect on the grain yield and other agronomic traits of barley (Hordeum vulgare L.). Environmental effects of the biofertilizer were also evaluated by following its influence on selected soil parameters. We applied the biofertilizer at five combinations of doses and timings each and in two application modes (foliar or direct soil application) within a randomized complete block design with three replicates and using a chemical fertilizer as control. The agronomic traits evaluated were plant height, root length, dry weight, and number of leaves and stems at three growth stages: tillering, jointing, and flowering. The effectiveness of the biofertilizer was significantly modified by the mode of application, the growth stage of the crop, and the dose of biofertilizer applied. The results showed that the foliar application of the biofertilizer at the tillering stage produced the highest increase in grain yield (59.7 %, p < 0.10). The use of the biofertilizer caused significant changes in soil, particularly concerning pH, EC, Ca, Zn, Mg, and Mn. It is our view that the production and use of biofertilizers are a reliable alternative to deal with a solid waste problem while food security is increased. PMID- 26545892 TI - Analysis of point source pollution and water environmental quality variation trends in the Nansi Lake basin from 2002 to 2012. AB - Based on the data analysis of the water environmental quality and economic development from 2002 to 2012 in the Nansi Lake basin, the correlation and change between the water environmental quality and economic development were studied. Results showed that the GDP and wastewater emissions of point source in the Nansi Lake basin had an average annual growth of 7.30 and 7.68 %, respectively, from 2002 to 2012. The emissions of chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) had the average annual decrease of 7.69 and 6.79 % in 2012, respectively, compared to 2002. Basin water quality overall improved, reaching the Class III of the "Environmental quality standards for surface water (GB3838-2002)," in which the main reason was that sewage treatment rate increased gradually and was above 90 % in 2012 (an increase of 10 % compared to 2002) with the progress of pollution abatement technology and the implementation of relevant policies and regulations. The contribution of water environmental pollution was analyzed from related cities (Ji'ning, Zaozhuang, Heze). Results indicated that Ji'ning had the largest contribution to water pollution of the Nansi Lake basin, and the pollutant from domestic sources accounted for a higher percentage compared to industrial sources. The wastewater, COD, and NH3-N mainly came from mining and washing of coal, manufacture of raw chemical materials and chemical products, papermaking industry, and food processing industry. According to the water pollution characteristics of the Nansi Lake basin, the basin pollution treatment strategy and prevention and treatment system were dissected to provide a scientific basis for prevention and control of lakeside point source pollution along the Nansi Lake. PMID- 26545893 TI - Sustainable remediation of mercury contaminated soils by thermal desorption. AB - Mercury soil contamination is an important environmental problem that needs the development of sustainable and efficient decontamination strategies. This work is focused on the application of a remediation technique that maintains soil ecological and environmental services to the extent possible as well as search for alternative sustainable land uses. Controlled thermal desorption using a solar furnace at pilot scale was applied to different types of soils, stablishing the temperature necessary to assure the functionality of these soils and avoid the Hg exchange to the other environmental compartments. Soil mercury content evolution (total, soluble, and exchangeable) as temperature increases and induced changes in selected soil quality indicators are studied and assessed. On total Hg, the temperature at which it is reduced until acceptable levels depends on the intended soil use and on how restrictive are the regulations. For commercial, residential, or industrial uses, soil samples should be heated to temperatures higher than 280 degrees C, at which more than 80 % of the total Hg is released, reaching the established legal total Hg level and avoiding eventual risks derived from high available Hg concentrations. For agricultural use or soil natural preservation, conversely, maintenance of acceptable levels of soil quality limit heating temperatures, and additional treatments must be considered to reduce available Hg. Besides total Hg concentration in soils, available Hg should be considered to make final decisions on remediation treatments and potential future uses. Graphical Abstract Solar energy use for remediation of soils affected by mercury. PMID- 26545894 TI - Embryotoxicity and genotoxicity evaluation of sediments from Yangtze River estuary using zebrafish (Danio rerio) embryos. AB - Sediments function both as a sink and a source of pollutants in aquatic ecosystems and may impose serious effects on benthic organisms and human health. As one of the largest estuaries in the world, the Yangtze River estuary suffers from abundant wastewater from the coastal cities. In this study, the zebrafish (Danio rerio) embryos were employed in the fish embryo test and a comet assay to evaluate the embryotoxicity and genotoxicity of the sediments from the Yangtze River estuary, respectively. Results showed that the sediments from the Yangtze River estuary significantly increased mortality, induced development abnormalities, and reduced hatching rate and heart rate of zebrafish embryos after 96 h of exposure. Significant genotoxicity was observed in the samples relative to the controls. Relatively low-level embryotoxicity and genotoxicity of sediments were found in the Yangtze River compared with other river systems. Toxic responses were also discussed in relation to the analyzed organic contaminants in sediments. More attention should be paid to non-priority pollutant monitoring in the Yangtze River estuary. PMID- 26545899 TI - CaMKII inhibition in type II pneumocytes protects from bleomycin-induced pulmonary fibrosis by preventing Ca2+-dependent apoptosis. AB - The calcium and calmodulin-dependent kinase II (CaMKII) translates increases in intracellular Ca(2+) into downstream signaling events. Its function in pulmonary pathologies remains largely unknown. CaMKII is a well-known mediator of apoptosis and regulator of endoplasmic reticulum (ER) Ca(2+). ER stress and apoptosis of type II pneumocytes lead to aberrant tissue repair and progressive collagen deposition in pulmonary fibrosis. Thus we hypothesized that CaMKII inhibition alleviates fibrosis in response to bleomycin by attenuating apoptosis and ER stress of type II pneumocytes. We first established that CaMKII was strongly expressed in the distal respiratory epithelium, in particular in surfactant protein-C-positive type II pneumocytes, and activated after bleomycin instillation. We generated a novel transgenic model of inducible expression of the CaMKII inhibitor peptide AC3-I limited to type II pneumocytes (Tg SPC-AC3-I). Tg SPC-AC3-I mice were protected from development of pulmonary fibrosis after bleomycin exposure compared with wild-type mice. CaMKII inhibition also provided protection from apoptosis in type II pneumocytes in vitro and in vivo. Moreover, intracellular Ca(2+) levels and ER stress were increased by bleomycin and significantly blunted with CaMKII inhibition in vitro. These data demonstrate that CaMKII inhibition prevents type II pneumocyte apoptosis and development of pulmonary fibrosis in response to bleomycin. CaMKII inhibition may therefore be a promising approach to prevent or ameliorate the progression of pulmonary fibrosis. PMID- 26545900 TI - Neutrophilic oxidative stress mediates organic dust-induced pulmonary inflammation and airway hyperresponsiveness. AB - Airway exposure to organic dust (OD) from swine confinement facilities induces airway inflammation dominated by neutrophils and airway hyperresponsiveness (AHR). One important neutrophilic innate defense mechanism is the induction of oxidative stress. Therefore, we hypothesized that neutrophils exacerbate airway dysfunction following OD exposure by increasing oxidant burden. BALB/C mice were given intranasal challenges with OD or PBS (1/day for 3 days). Mice were untreated or treated with a neutrophil-depleting antibody, anti-Ly6G, or the antioxidant dimethylthiourea (DMTU) prior to OD exposure. Twenty-four hours after the final exposure, we measured airway responsiveness in response to methacholine (MCh) and collected bronchoalveolar lavage fluid to assess pulmonary inflammation and total antioxidant capacity. Lung tissue was harvested to examine the effect of OD-induced antioxidant gene expression and the effect of anti-Ly6G or DMTU. OD exposure induced a dose-dependent increase of airway responsiveness, a neutrophilic pulmonary inflammation, and secretion of keratinocyte cytokine. Depletion of neutrophils reduced OD-induced AHR. DMTU prevented pulmonary inflammation involving macrophages and neutrophils. Neutrophil depletion and DMTU were highly effective in preventing OD-induced AHR affecting large, conducting airways and tissue elastance. OD induced an increase in total antioxidant capacity and mRNA levels of NRF-2-dependent antioxidant genes, effects that are prevented by administration of DMTU and neutrophil depletion. We conclude that an increase in oxidative stress and neutrophilia is critical in the induction of OD induced AHR. Prevention of oxidative stress diminishes neutrophil influx and AHR, suggesting that mechanisms driving OD-induced AHR may be dependent on neutrophil mediated oxidant pathways. PMID- 26545901 TI - N-cadherin coordinates AMP kinase-mediated lung vascular repair. AB - Injury to the pulmonary circulation compromises endothelial barrier function and increases lung edema. Resolution of lung damage involves restoring barrier integrity, a process requiring reestablishment of endothelial cell-cell adhesions. However, mechanisms underlying repair in lung endothelium are poorly understood. In pulmonary microvascular endothelium, AMP kinase alpha1 (AMPKalpha1) stimulation enhances recovery of the endothelial barrier after LPS induced vascular damage. AMPKalpha1 colocalizes to a discrete membrane compartment with the adhesion protein neuronal cadherin (N-cadherin). This study sought to determine N-cadherin's role in the repair process. Short-hairpin RNA against full-length N-cadherin or a C-terminally truncated N-cadherin, designed to disrupt the cadherin's interactions with intracellular proteins, were expressed in lung endothelium. Disruption of N-cadherin's intracellular domain caused translocation of AMPK away from the membrane and attenuated AMPK-mediated restoration of barrier function in LPS-treated endothelium. AMPK activity measurements indicated that lower basal AMPK activity in cells expressing the truncated N-cadherin compared with controls. Moreover, the AMPK stimulator 5 aminoimidazole-4-carboxamide ribonucleotide (AICAR) failed to increase AMPK activity in cells expressing the modified N-cadherin, indicating uncoupling of a functional association between AMPK and the cadherin. Isolated lung studies confirmed a physiologic role for this pathway in vivo. AMPK activation reversed LPS-induced increase in permeability, whereas N-cadherin inhibition hindered AMPK mediated repair. Thus N-cadherin coordinates the vascular protective actions of AMPK through a functional link with the kinase. This study provides insight into intrinsic repair mechanisms in the lung and supports AMPK stimulation as a modality for treating vascular disease. PMID- 26545902 TI - The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia. AB - Cystic fibrosis (CF), a genetic disease caused by mutations in the CFTR gene, is a life-limiting disease characterized by chronic bacterial airway infection and severe inflammation. Some CFTR mutants have reduced responsiveness to cAMP/PKA signaling; hence, pharmacological agents that elevate intracellular cAMP are potentially useful for the treatment of CF. By inhibiting cAMP breakdown, phosphodiesterase (PDE) inhibitors stimulate CFTR in vitro and in vivo. Here, we demonstrate that PDE inhibition by RPL554, a drug that has been shown to cause bronchodilation in asthma and chronic obstructive pulmonary disease (COPD) patients, stimulates CFTR-dependent ion secretion across bronchial epithelial cells isolated from patients carrying the R117H/F508del CF genotype. RPL554 induced CFTR activity was further increased by the potentiator VX-770, suggesting an additional benefit by the drug combination. RPL554 also increased cilia beat frequency in primary human bronchial epithelial cells. The results indicate RPL554 may increase mucociliary clearance through stimulation of CFTR and increasing ciliary beat frequency and thus could provide a novel therapeutic option for CF. PMID- 26545903 TI - Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung. AB - Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ~ 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung. PMID- 26545904 TI - BAG3-related myopathy, polyneuropathy and cardiomyopathy with long QT syndrome. AB - BAG3 belongs to BAG family of molecular chaperone regulators interacting with HSP70 and anti-apoptotic protein Bcl-2. It is ubiquitously expressed with strong expression in skeletal and cardiac muscle, and is involved in a panoply of cellular processes. Mutations in BAG3 and aberrations in its expression cause fulminant myopathies, presenting with progressive limb and axial muscle weakness, and respiratory insufficiency and neuropathy. Herein, we report a sporadic case of a 15-years old girl with symptoms of myopathy, demyelinating polyneuropathy and asymptomatic long QT syndrome. Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy. We did not find a mutation in any known LQT syndrome genes. Analysis of muscle biopsy revealed profound disintegration of Z-discs with extensive accumulation of granular debris and large inclusions within fibers. We demonstrated profound alterations in BAG3 distribution as the protein localized to long filamentous structures present across the fibers that were positively stained not only for alpha-actinin but also for desmin and filamin indicating that those disintegrated Z-disc regions contained also other sarcomeric proteins. The mutation caused a decrease in the content of BAG3 and HSP70, and also of alpha-actinin desmin, filamin and fast myosin heavy chain, confirming its severe effect on the muscle fiber morphology and thus function. We provide further evidence that BAG3 is associated with Z disc maintenance, and the Pro209Leu mutation may occur worldwide. We also provide a summary of cases associated with this mutation reported so far. PMID- 26545905 TI - Focus on osteo-ligamentous injuries around the ankle. PMID- 26545908 TI - Effects of the cestode parasite, Cyathocephalus truncatus, on the fecundity and feeding rate of Gammarus pulex (Crustacea: Amphipoda). AB - The amphipod Gammarus pulex is an intermediate host to the Cestode fish parasite Cyathocephalus truncatus. In this study, we investigate effect of parasitism on female fecundity and feeding rate and compare ours results to those obtained previously with acanthocephalan parasite. Similar reduction of the female fecundity was measured, whereas ours results on feeding rate were inconsistent, with a decrease of feeding rate induced by C. truncatus. The impacts of C. truncatus on G. pulex and similarities on the host infection effect between parasites from different phyla are discussed. PMID- 26545907 TI - Oxidative stress is associated with weight gain in recipients at 12-months following kidney transplantation. AB - OBJECTIVE: Weight gain after kidney transplantation (Tx) is considered a risk factor for poor outcomes. Increased oxidative stress is associated with not only chronic renal disease and Tx, but also obesity and cardiovascular disease. The aim of this pilot study was to test whether oxidative stress is related to weight gain at 12-months after kidney Tx and to obtain preliminary insight into potential mechanisms involved. DESIGN & METHODS: Recipients (n=33) were classified into two groups; weight loss and weight gain, based on their weight changes at 12-months post-transplant. Total antioxidant capacity (TAOC) and lipid peroxidation (TBARS) were measured to evaluate oxidative stress from plasma at baseline and 12-months. A secondary data analysis was conducted to identify potential gene regulation. RESULTS: Seventeen recipients lost (-6.63+/-5.52kg), and sixteen recipients gained weight (8.94+/-6.18kg). TAOC was significantly decreased at 12-months compared to baseline for the total group, however, there was no significant difference between groups at either time point. TBARS was higher in weight gain group, at both time points, and it was significantly higher at 12-months (p=0.012). Gene expression profiling analysis showed that 7 transcripts annotated to reactive oxygen species related genes in adipose tissue were expressed significantly lower in weight gain group at baseline, which might be a negative feedback mechanism to reduce oxidative stress. CONCLUSION: These results may indicate that elevated oxidative stress (TBARS) is associated with weight gain after kidney Tx and that incorporating early clinical prevention strategies known to decrease oxidative stress could be recommended. PMID- 26545909 TI - Improvement on the extraction method of RNA in mites and its quality test. AB - To solve the long-existing difficult problems in extracting RNA and constructing a complementary DNA (cDNA) library for trace mites, we conducted a further comparative experiment among three RNA extraction methods (TRIzol method, Omega method, and Azanno method) based on our previous attempts at the construction of cDNA library of mites, with Psoroptes cuniculi still used as the experimental subject. By subsequently decreasing the number of mites, the least number of mites needed for RNA extraction of each method were found by criteria of completeness, concentration, and purity of the extracted RNA. Specific primers were designed according to the allergen Pso c1, Pso c2, and Actin gene sequences of Psoroptes to test the reliability of cDNA library. The results showed that Azanno method needed only 10 mites with sensitivity 204 times higher than previously used TRIzol method and 20 times higher than Omega method; clear RNA band was detected by agarose gel electrophoresis; and ultraviolet spectrophotometer determination showed that RNA concentration, 260/280, and 260/230 were in the range of 102 to 166 ng/MUl, 1.83 to 1.99, and 1.49 to 1.72, respectively. Finally, specific primers detection showed that the amplified sequences had 98.33, 98.19, and 99.52% identities with those of P. cuniculi or Psoroptes ovis in GenBank, respectively, indicating that the cDNA library constructed using 10 mites was successful and it could meet the requirements for molecular biology research. Therefore, we concluded that Azanno method was more effective than TRIzol method and Omega method in RNA extraction and cDNA library construction of trace mites. PMID- 26545910 TI - A case study of machinery maintenance protocols and procedures within the UK utilities sector. AB - Failure to conduct periodic fixed-time-to (or scheduled) maintenance on off highway plant and equipment represents a significant health and safety hazard and major litigation risk for utility contractors completing service excavation and reinstatement works on public highways. Mini-excavators are a ubiquitous mobile plant item used for such tasks and have recently been responsible for several major injuries and fatalities involving workers and members of the public in the United Kingdom (UK). The research utilises the method of triangulation to examine the maintenance practices of utility contractors in the UK. Findings from the research reveal that a combination of prevailing market forces and internal 'company' pressures have inadvertently removed knowledgeable and trained operators, site foremen and managerial supervisors from hands-on maintenance inspections. Rather, 'virtual' maintenance protocols and procedures are adopted by head office but rarely fully implemented on-site. The research concludes with pragmatic recommendations and direction for future research. PMID- 26545911 TI - Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients. AB - PURPOSE: The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. METHODS: A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), beta-fibrinogen (-455G -> A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. RESULTS: Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. CONCLUSIONS: Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated. PMID- 26545912 TI - Project SMART: Preliminary Results From a Test of the Efficacy of a Swedish Internet-Based HIV Risk-Reduction Intervention for Men Who Have Sex With Men. AB - In Sweden, 57 % of HIV transmission occurs among MSM, and other sexually transmitted infections are increasing, supporting the need for innovative interventions. The Internet is a potentially useful HIV-prevention platform, but there is a lack of such programs in Sweden. The purpose of this exploratory study was to test the efficacy of the Internet-based SMART intervention to decrease HIV sexual risks in Swedish MSM. The intervention was adapted from the Wyoming Rural AIDS Prevention Project to the Swedish context, which was guided by the Information-Motivation-Behavioral (IMB) skills model and consisted of six sessions. A total of 112 men responded to a pretest questionnaire and were randomly assigned to the SMART intervention or to a waitlist group. Fifty-four men dropped out, leaving a final sample of 58 participants. Twenty-five were assigned to the SMART intervention and 33 to a waitlist group. One month post intervention, the number of casual anal sex partners significantly decreased (t = 2.19, p = .04). Compared with the waitlist group, men in the intervention group increased their HIV knowledge (beta = 0.70, p = .01), their belief of condom use as an act of responsibility (beta = 1.19, p = .04), their willingness to use a condom with every new partner all the time (beta = 1.39, p = .03), and their confidence in using condoms in challenging situations (beta = 1.65, p = .02). Condom use was not analyzed due to the small sample size. Despite the small sample, high drop-out, and short follow-up, the study provides support for the efficacy of the Internet interventions, the SMART intervention specifically, for reducing the proportion of casual anal sex partners and improving the three cognitive components of the IMB model for Swedish MSM. PMID- 26545913 TI - Identification with Stimuli Moderates Women's Affective and Testosterone Responses to Self-Chosen Erotica. AB - Sexual thoughts are sufficient to increase testosterone (T) in women, yet erotic films are not. A key confound in past studies is autonomy in stimulus selection: women choose the content of their sexual thoughts but films have been selected by researchers. We hypothesized that self-chosen erotic films, compared to researcher-chosen erotic films, would (1) increase women's self-reported arousal, enjoyment, and identification with stimuli, and decrease negative affect; and (2) increase T. Participants (N = 116 women) were randomly assigned to a neutral documentary condition or one of three erotic film conditions: high choice (self chosen erotica from participants' own sources), moderate choice (self-chosen erotica from films preselected by sexuality researchers), or no choice (researcher-chosen erotica). Participants provided saliva samples for T before and after viewing the film in the privacy of their homes. Compared to researcher chosen erotica, self-chosen erotica increased self-reported arousal and enjoyment, but also unexpectedly disgust, guilt, and embarrassment. Self-chosen erotica only marginally increased identification with stimuli compared to researcher-chosen erotica. Overall, film condition did not affect T, but individual differences in identification moderated T responses: among women reporting lower levels of identification, the moderate choice condition decreased T compared to the no choice condition, but this difference was not observed among women with higher identification. These results highlight the importance of cognitive/emotional factors like identification for sexually modulated T. However, self-chosen erotica results in more ambivalent rather than unequivocally positive cognitive/emotional responses, perhaps because stigma associated with viewing erotica for women becomes more salient when choosing stimuli. PMID- 26545914 TI - An Interpersonal Investigation of Sexual Self-Schemas. AB - A sexual self-schema is a cognitive generalization about sexual aspects of the self. In the current study, we examined how an individual's sexual self-schema influenced the processing of self and partner related sexual information. Specifically, we investigated how sexual self-schemas related to own and partner sexual satisfaction and how they influenced perceptions of partner sexual satisfaction. Participants were 117 heterosexual couples in committed, long-term relationships. Both partners completed measures assessing their sexual self schemas, their own sexual satisfaction, and perceptions of partner sexual satisfaction. Consistent with our predictions, own sexual schema was associated with own sexual satisfaction. For men, more positive sexual self-schemas were associated with greater sexual satisfaction, and for women, more negative sexual self-schemas were associated with lower sexual satisfaction. For both men and women, there was no significant association between own sexual self-schema and partner sexual satisfaction. Sexual self-schemas directly and indirectly influenced an individual's perception of the partner's sexual satisfaction, such that men and women with more positive sexual self-schemas rated their partners as more sexually satisfied, after controlling for the partner's self-reported level of sexual satisfaction. Our findings demonstrated that sexual self-schemas are relevant to own sexual satisfaction as well as the processing of interpersonally relevant sexual information, specifically one's perceptions of partner sexual satisfaction. PMID- 26545916 TI - Involvement of dietary saturated fats, from all sources or of dairy origin only, in insulin resistance and type 2 diabetes. AB - Reducing the consumption of saturated fatty acids to a level as low as possible is a European public health recommendation to reduce the risk of cardiovascular disease. The association between dietary intake of saturated fatty acids and development and management of type 2 diabetes mellitus (T2DM), however, is a matter of debate. A literature search was performed to identify prospective studies and clinical trials in humans that explored the association between dietary intake of saturated fatty acids and risk of insulin resistance and T2DM. Furthermore, to assess whether specific foods, and not just the saturated fatty acid content of the food matrix, can have differential effects on human health, the relationship between consumption of full-fat dairy products, a main source of dietary saturated fatty acids, and risk of insulin resistance and T2DM was studied. There is no evidence that dietary saturated fatty acids from varied food sources affect the risk of insulin resistance or T2DM, nor is intake of full-fat dairy products associated with this risk. These findings strongly suggest that future studies on the effects of dietary saturated fatty acids should take into account the complexity of the food matrix. Furthermore, communication on saturated fats and their health effects should be prudent and well informed. PMID- 26545915 TI - Epoxyeicosanoid Signaling Provides Multi-target Protective Effects on Neurovascular Unit in Rats After Focal Ischemia. AB - Multiple players are involved in the highly complex pathophysiologic responses after stroke. Therefore, therapeutic approaches that target multiple cellular elements of the neurovascular unit in the damage cascade hold considerable promise for the treatment of stroke. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active eicosanoids called epoxyeicosatrienoic acids (EETs), which are further converted by soluble epoxide hydrolase (sEH) to less bioactive diols. EETs have been shown to exert direct cytoprotective effects upon several individual components of the neurovascular unit under simulated ischemic conditions in vitro. However, the cellular mechanism underlying EET-mediated neuroprotective effects after ischemia remains to be clarified. In this study, we investigated the effects of 14,15-EET and 12 (3-adamantan-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of sEH, on multiple elements of neurovascular unit of the rat brain after middle cerebral artery occlusion-induced focal ischemia. The results showed that exogenous administration of 14,15-EET or AUDA could suppress astrogliosis and glial scar formation, inhibit microglia activation and inflammatory response, promote angiogenesis, attenuate neuronal apoptosis and infarct volume, and further promote the behavioral function recovery after focal ischemia. The results suggest that epoxyeicosanoid signaling is a promising multi-mechanism therapeutic target for the treatment of stroke. PMID- 26545918 TI - Cyclostomes Lack Clustered Protocadherins. AB - The brain, comprising billions of neurons and intricate neural networks, is arguably the most complex organ in vertebrates. The diversity of individual neurons is fundamental to the neuronal network complexity and the overall function of the vertebrate brain. In jawed vertebrates, clustered protocadherins provide the molecular basis for this neuronal diversity, through stochastic and combinatorial expression of their various isoforms in individual neurons. Based on analyses of transcriptomes from the Japanese lamprey brain and sea lamprey embryos, genome assemblies of the two lampreys, and brain expressed sequence tags of the inshore hagfish, we show that extant jawless vertebrates (cyclostomes) lack the clustered protocadherins. Our findings indicate that the clustered protocadherins originated from a nonclustered protocadherin in the jawed vertebrate ancestor, after the two rounds of whole-genome duplication. In the absence of clustered protocadherins, cyclostomes might have evolved novel molecules or mechanisms for generating neuronal diversity which remains to be discovered. PMID- 26545917 TI - Iron-Sulfur Cluster Biogenesis Chaperones: Evidence for Emergence of Mutational Robustness of a Highly Specific Protein-Protein Interaction. AB - Biogenesis of iron-sulfur clusters (FeS) is a highly conserved process involving Hsp70 and J-protein chaperones. However, Hsp70 specialization differs among species. In most eukaryotes, including Schizosaccharomyces pombe, FeS biogenesis involves interaction between the J-protein Jac1 and the multifunctional Hsp70 Ssc1. But, in Saccharomyces cerevisiae and closely related species, Jac1 interacts with the specialized Hsp70 Ssq1, which emerged through duplication of SSC1. As little is known about how gene duplicates affect the robustness of their protein interaction partners, we analyzed the functional and evolutionary consequences of Ssq1 specialization on the ubiquitous J-protein cochaperone Jac1, by comparing S. cerevisiae and S. pombe. Although deletion of JAC1 is lethal in both species, alanine substitutions within the conserved His-Pro-Asp (HPD) motif, which is critical for Jac1:Hsp70 interaction, have species-specific effects. They are lethal in S. pombe, but not in S. cerevisiae. These in vivo differences correlated with in vitro biochemical measurements. Charged residues present in the J-domain of S. cerevisiae Jac1, but absent in S. pombe Jac1, are important for tolerance of S. cerevisiae Jac1 to HPD alterations. Moreover, Jac1 orthologs from species that encode Ssq1 have a higher sequence divergence. The simplest interpretation of our results is that Ssq1's coevolution with Jac1 resulted in expansion of their binding interface, thus increasing the efficiency of their interaction. Such an expansion could in turn compensate for negative effects of HPD substitutions. Thus, our results support the idea that the robustness of Jac1 emerged as consequence of its highly efficient and specific interaction with Ssq1. PMID- 26545919 TI - Determinants of the Usage of Splice-Associated cis-Motifs Predict the Distribution of Human Pathogenic SNPs. AB - Where in genes do pathogenic mutations tend to occur and does this provide clues as to the possible underlying mechanisms by which single nucleotide polymorphisms (SNPs) cause disease? As splice-disrupting mutations tend to occur predominantly at exon ends, known also to be hot spots of cis-exonic splice control elements, we examine the relationship between the relative density of such exonic cis motifs and pathogenic SNPs. In particular, we focus on the intragene distribution of exonic splicing enhancers (ESE) and the covariance between them and disease associated SNPs. In addition to showing that disease-causing genes tend to be genes with a high intron density, consistent with missplicing, five factors established as trends in ESE usage, are considered: relative position in exons, relative position in genes, flanking intron size, splice sites usage, and phase. We find that more than 76% of pathogenic SNPs are within 3-69 bp of exon ends where ESEs generally reside, this being 13% more than expected. Overall from enrichment of pathogenic SNPs at exon ends, we estimate that approximately 20-45% of SNPs affect splicing. Importantly, we find that within genes pathogenic SNPs tend to occur in splicing-relevant regions with low ESE density: they are found to occur preferentially in the terminal half of genes, in exons flanked by short introns and at the ends of phase (0,0) exons with 3' non-"AGgt" splice site. We suggest the concept of the "fragile" exon, one home to pathogenic SNPs owing to its vulnerability to splice disruption owing to low ESE density. PMID- 26545920 TI - Expansion of Noncanonical V-Arm-Containing tRNAs in Eukaryotes. AB - Transfer RNA (tRNA) is essential for the translation of genetic information into proteins, and understanding its molecular evolution is important if we are to understand the genetic code. In general, long variable-arm (V-arm) structures form in tRNA(Leu), tRNA(Ser), and bacterial and organellar tRNA(Tyr). However, as we have previously reported, noncanonical V-arms occur in nematode tRNA(Gly) and tRNA(Ile), and potentially affect translational fidelity. Here, we comprehensively analyzed 69 eukaryotic genome sequences and examined the evolutionary divergence of the V-arm-containing tRNAs. In total, 253 V-arm containing tRNAs, with neither leucine nor serine anticodons, were identified in organisms ranging from nematodes to fungi, plants, and vertebrates. We defined them as "noncanonical V-arm-containing tRNAs" (nov-tRNAs). Moreover, 2,415 nov tRNA-like sequences lacking some of the conserved features of tRNAs were also identified, largely in vertebrate genomes. These nov-tRNA/nov-tRNA-like sequences can be categorized into three types, based on differences in their possible evolutionary origins. The type A nov-tRNAs in nematodes probably evolved not only from tRNA(Leu) but also from tRNA(Ser) and other isotypes on several independent occasions. The type B nov-tRNAs are dispersed abundantly throughout vertebrate genomes, and seem to have originated from retrotransposable elements. The type C nov-tRNAs may have been acquired from plant chloroplasts or from bacteria through horizontal transfer. Our findings provide unexpected insight into the evolution of the tRNA molecule, which was diverse and occurred independently in nematodes, vertebrates, and plants. PMID- 26545922 TI - Computationally Efficient Composite Likelihood Statistics for Demographic Inference. AB - Many population genetics tools employ composite likelihoods, because fully modeling genomic linkage is challenging. But traditional approaches to estimating parameter uncertainties and performing model selection require full likelihoods, so these tools have relied on computationally expensive maximum-likelihood estimation (MLE) on bootstrapped data. Here, we demonstrate that statistical theory can be applied to adjust composite likelihoods and perform robust computationally efficient statistical inference in two demographic inference tools: ?a?i and TRACTS. On both simulated and real data, the adjustments perform comparably to MLE bootstrapping while using orders of magnitude less computational time. PMID- 26545923 TI - Reply to comment on: The spontaneous coronary artery dissection may need intervention in the proximal segment of the arteries by Associate Professor Ozturk. PMID- 26545921 TI - Estimating the Ages of Selection Signals from Different Epochs in Human History. AB - Genetic variation harbors signatures of natural selection driven by selective pressures that are often unknown. Estimating the ages of selection signals may allow reconstructing the history of environmental changes that shaped human phenotypes and diseases. We have developed an approximate Bayesian computation (ABC) approach to estimate allele ages under a model of selection on new mutations and under demographic models appropriate for human populations. We have applied it to two resequencing data sets: An ultra-high depth data set from a relatively small sample of unrelated individuals and a lower depth data set in a larger sample with transmission information. In addition to evaluating the accuracy of our method based on simulations, for each SNP, we assessed the consistency between the posterior probabilities estimated by the ABC approach and the ancient DNA record, finding good agreement between the two types of data and methods. Applying this ABC approach to data for eight single nucleotide polymorphisms (SNPs), we were able to rule out an onset of selection prior to the dispersal out-of-Africa for three of them and more recent than the spread of agriculture for an additional three SNPs. PMID- 26545924 TI - Response to letter: Duration of dual antiplatelet therapy following drug-eluting coronary stents: Longer or shorter? PMID- 26545925 TI - Device therapy and aldosterone antagonists in the prognosis of heart failure. PMID- 26545926 TI - Cardiac cachexia: hic et nunc: "hic et nunc" - here and now. AB - Cardiac cachexia (CC) is the clinical entity at the end of chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. Better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick-up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID- 26545927 TI - Using Twitter Data to Gain Insights into E-cigarette Marketing and Locations of Use: An Infoveillance Study. AB - BACKGROUND: Marketing and use of electronic cigarettes (e-cigarettes) and other electronic nicotine delivery devices have increased exponentially in recent years fueled, in part, by marketing and word-of-mouth communications via social media platforms, such as Twitter. OBJECTIVE: This study examines Twitter posts about e cigarettes between 2008 and 2013 to gain insights into (1) marketing trends for selling and promoting e-cigarettes and (2) locations where people use e cigarettes. METHODS: We used keywords to gather tweets about e-cigarettes between July 1, 2008 and February 28, 2013. A randomly selected subset of tweets was manually coded as advertising (eg, marketing, advertising, sales, promotion) or nonadvertising (eg, individual users, consumers), and classification algorithms were trained to code the remaining data into these 2 categories. A combination of manual coding and natural language processing methods was used to indicate locations where people used e-cigarettes. Additional metadata were used to generate insights about users who tweeted most frequently about e-cigarettes. RESULTS: We identified approximately 1.7 million tweets about e-cigarettes between 2008 and 2013, with the majority of these tweets being advertising (93.43%, 1,559,508/1,669,123). Tweets about e-cigarettes increased more than tenfold between 2009 and 2010, suggesting a rapid increase in the popularity of e cigarettes and marketing efforts. The Twitter handles tweeting most frequently about e-cigarettes were a mixture of e-cigarette brands, affiliate marketers, and resellers of e-cigarette products. Of the 471 e-cigarette tweets mentioning a specific place, most mentioned e-cigarette use in class (39.1%, 184/471) followed by home/room/bed (12.5%, 59/471), school (12.1%, 57/471), in public (8.7%, 41/471), the bathroom (5.7%, 27/471), and at work (4.5%, 21/471). CONCLUSIONS: Twitter is being used to promote e-cigarettes by different types of entities and the online marketplace is more diverse than offline product offerings and advertising strategies. E-cigarettes are also being used in public places, such as schools, underscoring the need for education and enforcement of policies banning e-cigarette use in public places. Twitter data can provide new insights on e-cigarettes to help inform future research, regulations, surveillance, and enforcement efforts. PMID- 26545928 TI - TSPO in a murine model of Sandhoff disease: presymptomatic marker of neurodegeneration and disease pathophysiology. AB - Translocator protein (18 kDa), formerly known as the peripheral benzodiazepine receptor (PBR), has been extensively used as a biomarker of active brain disease and neuroinflammation. TSPO expression increases dramatically in glial cells, particularly in microglia and astrocytes, as a result of brain injury, and this phenomenon is a component of the hallmark response of the brain to injury. In this study, we used a mouse model of Sandhoff disease (SD) to assess the longitudinal expression of TSPO as a function of disease progression and its relationship to behavioral and neuropathological endpoints. Focusing on the presymptomatic period of the disease, we used ex vivo [(3)H]DPA-713 quantitative autoradiography and in vivo [(125)I]IodoDPA-713 small animal SPECT imaging to show that brain TSPO levels markedly increase prior to physical and behavioral manifestation of disease. We further show that TSPO upregulation coincides with early neuronal GM2 ganglioside aggregation and is associated with ongoing neurodegeneration and activation of both microglia and astrocytes. In brain regions with increased TSPO levels, there is a differential pattern of glial cell activation with astrocytes being activated earlier than microglia during the progression of disease. Immunofluorescent confocal imaging confirmed that TSPO colocalizes with both microglia and astrocyte markers, but the glial source of the TSPO response differs by brain region and age in SD mice. Notably, TSPO colocalization with the astrocyte marker GFAP was greater than with the microglia marker, Mac-1. Taken together, our findings have significant implications for understanding TSPO glial cell biology and for detecting neurodegeneration prior to clinical expression of disease. PMID- 26545929 TI - Predictors of the necessity for lymph node biopsy of cervical lymphadenopathy. AB - PURPOSE: Enlargement of cervical lymph nodes is required for early and accurate diagnosis of malignant lymphoma (ML). Lymph node biopsy is still indispensable for accurate diagnosis of lymph node enlargement in the lateral neck. MATERIAL AND METHODS: We retrospectively investigated the characteristics of lymph nodes on both ultrasonography (US) and computed tomography (CT), and blood biomarkers including serum thymidine kinase (TK) and soluble interleukin-2 receptor (sIL-2R) in 19 patients who underwent cervical lymph node biopsy. RESULTS: Pathological diagnosis was ML in 8 patients, reactive lymphadenopathy (RL) in 8, and purulent lymphadenitis (PL) in 3. TK levels were significantly higher in patients with ML than in patients with RL, demonstrating positive correlations with sIL-2R and lymph node size on CT image. The shape of lymph nodes on US in all of the 8 patients diagnosed with RL was flat, whereas the shape in 7 of 8 patients diagnosed with ML was round. Lymph node size >=19.5 mm at an axial section on CT image was used as a cut-off value to differentiate ML from other pathologies, offering 90.9% sensitivity and 87.5% specificity. CONCLUSION: Sonographic and CT evaluation combined with high TK level might be useful in determining the need for early biopsy. PMID- 26545930 TI - The effect of early routine grommet insertion on management of otitis media with effusion in children with cleft palate. AB - PURPOSE: The aim of the study is to compare long term otoscopic and audiological findings of cleft palate patients with or without early grommet insertion. METHODS: Cleft palate patients followed-up in Hacettepe University between 2008 and 2013 were included in the study. Age, gender, cleft types and palate surgery data, grommet tube insertion history and otological - audiological evaluations of the patients were recorded. Patients were evaluated in three groups according to grommet insertion history: A-early routine grommet insertion, B-grommet insertion during follow-up, C-no grommet insertion. Otological and audiological findings were compared. RESULTS: There were 154 patients in the study, with a median age of 7.7 years. There were 67 patients in group A (43.5%), 22 patients in group B (14.3%) and 65 patients in group C (42.2%). OME was identified significantly higher in group A and normal otoscopic examination findings were higher in group C. Complications showed a higher rate than other otoscopic findings in group B patients. There was no significant difference for any frequencies in between the groups in terms of mean air-bone gap (ABG) values. There were 20 grade I, 25 grade II, 77 grade III and 32 grade IV patients in the study according to the Veau classification. CONCLUSION: Prophylactic grommet insertion may not be applied as some cleft palate patients with no OME. Wait and see protocol can be recommended for these patients, and they should be followed-up up closely to avoid complications. If the effusion does not recover or tympanic membrane changes occur in follow-up, grommet insertion should be considered. PMID- 26545931 TI - Does arteriosclerosis contribute to hemifacial spasm? AB - BACKGROUND: Hemifacial spasm (HFS) is caused by pulsative vascular compression of the root exit zone (REZ) of the facial nerve. However, the mechanism that causes the offending vessels to compress the REZ has not been clarified. Elongation of intracranial arteries due to arteriosclerosis is one possibility, but such arteriosclerotic changes are not observed very frequently among patients with HFS. The aim of the present study was to investigate whether arteriosclerotic changes would contribute to the pathogenesis of HFS. METHODS: This study included 111 HFS patients, all of whom were Japanese. The prevalence rates of hypertension, hyperlipidemia, and diabetes mellitus were examined as risk factors of atherosclerosis, and the cardio-ankle vascular index (CAVI) was measured as an indicator of arteriosclerotic change. The severity of white matter lesions (WMLs) in HFS patients was measured by magnetic resonance imaging. These data were compared with data from healthy Japanese controls. RESULTS: The prevalence rates of the risk factors for atherosclerosis in the HFS patients were not higher than those in the general Japanese population. The CAVI scores for the HFS patients were similar to, or lower than those in the healthy controls for all age groups except 60 to 69-year-old men. The severity of WMLs in the HFS patients was not significantly worse than that in the controls. CONCLUSIONS: It is suggested that arteriosclerotic changes are not involved in the pathogenesis of HFS, and that vascular compression syndromes are attributable to anatomical features of the intracranial arteries and facial nerves formed during the prenatal stage. PMID- 26545933 TI - A prospective cohort study of early postpartum etonogestrel implant (Implanon(r)) use and its effect on duration of lochia. AB - BACKGROUND: Etonogestrel (ENG) implants (Implanon((r))/Nexplanon((r))/Implanon NXT((r))) are employed as contraception in early postpartum patients. Follow-up is often not conducted by the hospital prescriber. Little is known about duration of lochia, in a modern setting, and even less is known about the effect of ENG implants on lochia. AIMS: To determine if early postpartum (pre-discharge) insertion of Implanon for contraception was associated with a significant difference in duration of lochia. To record the number of patients who went on to have their Implanon removed during the study period and the reasons for removal. METHODS: Prospective cohort study of 152 postpartum patients from a tertiary maternity unit in Hobart, Tasmania, Australia. The treatment group was women requesting Implanon prior to discharge. Controls were recruited from the same unit over the same time period, with the aim to match for birth weight and parity. Information was collected during face-to-face interviews or via telephone contact. Multivariate survival analysis was used to investigate lochia duration. RESULTS: There were 73 controls and 79 women who had early postpartum Implanon inserted. Fourteen (17.7%) patients in the treatment group had their Implanon removed during the postpartum study period. In all of these cases the reason for removal was bleeding disturbance - prolonged or intermittent vaginal bleeding beyond 50 days postpartum. There was no significant difference in duration of lochia between the groups [median predicted duration 25 days (95% CI 22-27) in controls and 24 days (95% CI 21-26) in the treatment group]. CONCLUSIONS: Early postpartum insertion of Implanon for contraception was not associated with a statistically or clinically significant difference in duration of lochia. PMID- 26545932 TI - Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases. AB - Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects. PMID- 26545935 TI - De novo transcriptome assembly and identification of genes associated with feed conversion ratio and breast muscle yield in domestic ducks. AB - Breast muscle yield and feed conversion efficiency are the major breeding aims in duck breeding. Understanding the role of specific transcripts in the muscle and small intestine might lead to the elucidation of interrelated biological processes. In this study, we obtained jejunum and breast muscle samples from two strains of Peking ducks that were sorted by feed conversion ratio (FCR) and breast muscle percentage into two-tailed populations. Ten RNA-Seq libraries were developed from the pooled samples and sequenced using the Hiseq2000 platform. We created a reference duck transcript database using de novo assembly methods, which included 16 663 irredundant contigs with an N50 length of 1530 bp. This new duck reference cDNA dataset significantly improved the mapping rate for RNA-Seq data, from 50% to 70%. Mapping and annotation were followed by Gene Ontology analysis, which showed that numerous genes were differentially expressed between the low and high FCR groups. The differentially expressed genes in the jejunum were enriched in biological processes related to immune response and immune response activation, whereas those in the breast muscle were significantly enriched in biological processes related to muscle cell differentiation and organ development. We identified new candidate genes, that is, PCK1, for improving the FCR and breast muscle yield of ducks and obtained much better reference duck transcripts. This study suggested that de novo assembly is essential when applying transcriptome analysis to a species with an incomplete genome. PMID- 26545934 TI - Antitumor effect of afatinib, as a human epidermal growth factor receptor 2 targeted therapy, in lung cancers harboring HER2 oncogene alterations. AB - Human epidermal growth factor receptor 2 (HER2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It plays an important role in the pathogenesis of certain human cancers. In non-small-cell lung cancer (NSCLC), HER2 amplification or mutations have been reported. However, little is known about the benefit of HER2-targeted therapy for NSCLCs harboring HER2 alterations. In this study, we investigated the antitumor effect of afatinib, an irreversible epidermal growth factor receptor (EGFR)-HER2 dual inhibitor, in lung cancers harboring HER2 oncogene alterations, including novel HER2 mutations in the transmembrane domain, which we recently identified. Normal bronchial epithelial cells, BEAS-2B, ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, and G660D) showed constitutive autophosphorylation of HER2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to gefitinib. Furthermore, we examined the antitumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alterations and sensitivity to afatinib treatment. In HER2-altered NSCLC cells (H2170, Calu-3, and H1781), afatinib downregulated the phosphorylation of HER2 and EGFR as well as their downstream signaling, and induced an antiproliferative effect through G1 arrest and apoptotic cell death. In contrast, HER2- or EGFR-non-dependent NSCLC cells were insensitive to afatinib. In addition, these effects were confirmed in vivo by using a xenograft mouse model of HER2-altered lung cancer cells. Our results suggest that afatinib is a therapeutic option as a HER2-targeted therapy for NSCLC harboring HER2 amplification or mutations. PMID- 26545936 TI - [Work-related mental and behaviour disorders in anesthesiologists]. AB - BACKGROUND: Anaesthesiology is a specialty whose specificity of the working process results in high levels of stress as an inevitable condition - a particularly worrying situation in the daily life of these professionals. OBJECTIVES: This study, based on data from national and international literature, aims to discuss the basis of the occurrence of mental and behavioural disorders or of psychopathological injuries (psychological distress) related to working activity in anesthesiologists. METHOD: A literature review was conducted, with papers selected from Medline and Lilacs databases, published between 2000 and 2012 in Portuguese, English and Spanish, and addressing the possible association between occupational hazards of the anaesthesiologist profession and mental health problems and psychic distress. Twenty-six publications were listed. RESULTS: Several aspects of the anesthesiologist's work are important points to better understand the relationship between mental health at work and working organization. Poor temporal structuring of work, conflictuous interpersonal relationships and poor control over the activity itself may be mentioned as illness enhancers. CONCLUSION: The working organization, when not appropriate, is an important occupational risk factor for the life and mental health of workers, mainly of professionals focused on the care of people. This paper focuses on anesthesiologists, who are constantly exposed to stressful and anxiogenic factors. PMID- 26545937 TI - The system-resonance approach in modeling genetic structures. AB - The founder of the theory of resonance in structural chemistry Linus Pauling established the importance of resonance patterns in organization of living systems. Any living organism is a great chorus of coordinated oscillatory processes. From the formal point of view, biological organism is an oscillatory system with a great number of degrees of freedom. Such systems are studied in the theory of oscillations using matrix mathematics of their resonance characteristics. This study is devoted to a new approach for modeling genetically inherited structures and processes in living organisms using mathematical tools of the theory of resonances. This approach reveals hidden relationships in a number of genetic phenomena and gives rise to a new class of bio-mathematical models, which contribute to a convergence of biology with physics and informatics. In addition some relationships of molecular-genetic ensembles with mathematics of noise-immunity coding of information in modern communications technology are shown. Perspectives of applications of the phenomena of vibrational mechanics for modeling in biology are discussed. PMID- 26545938 TI - Paroxysmal atrial fibrillation: A window of opportunity to modify disease progression. PMID- 26545939 TI - Comparative long-term outcomes after cardiac resynchronization therapy in right ventricular paced patients versus native wide left bundle branch block patients. AB - BACKGROUND: The current guidelines do not clearly state when we should upgrade a patient with right ventricular pacing (RVP) to cardiac resynchronization therapy (CRT), although the deleterious effect of chronic RVP has been established with recent trials. OBJECTIVES: The aims of this study were to compare the long-term survival after CRT in patients upgraded from RVP with that in patients with left bundle branch block (LBBB) with QRS duration >= 150 ms and to compare the mechanical properties associated with CRT response in these groups. METHODS: Overall, 135 patients with implanted CRT from a single center (85 (63%) with native wide LBBB and 50 (37%) with RVP) were studied prospectively. Baseline left ventricular typical contraction pattern was determined using speckle tracking echocardiography in the apical 4-chamber view. The predefined end point was death, heart transplantation, or left ventricular assist device implantation over a period of 4 years. RESULTS: Patients with RVP had a significantly favorable long-term outcomes with adjusted hazard ratio of 0.36 (95% confidence interval 0.14-0.96; P = .04). Both groups had ~70% of patients with typical contraction pattern. The absence of typical contraction pattern was associated with a higher risk of an end point with adjusted hazard ratio of 5.43 (95% confidence interval 2.31-12.72; P < .001). In patients with typical contraction pattern, activation of the apical septal segment occurred more frequently in the RVP group and of the base or mid septal segments in the LBBB group. CONCLUSION: Patients with HF upgraded from RVP have more favorable long-term outcomes after CRT than do native LBBB patients with QRS duration >= 150 ms. Contraction pattern assessment can be used to identify potential responders in the RVP group. PMID- 26545940 TI - 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. AB - OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (>=6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies. PMID- 26545941 TI - Osteoid osteoma of the glenoid: Arthroscopic treatment. AB - Osteoid osteoma is a benign tumor that is rarely found in the scapula. We report a clinical case involving a 36-year-old female patient who suffered from progressive pain in her right shoulder for 1 year. This patient was initially diagnosed with impingement syndrome and was treated unsuccessfully with medication and physical therapy for approximately 2 months. Based on imaging exams, a juxta-articular osteoid osteoma of the glenoid was identified. The patient underwent a shoulder arthroscopy that included tumor removal and treatment of the resulting chondral lesion. At 6-, 12- and 36-month assessments, the patient was asymptomatic, with a normal range of motion and experienced a pain intensity corresponding to 0 points on the Visual Analog Scale (VAS) and 35 points on the University of California, Los Angeles (UCLA) Scale. A postoperative MRI indicated the absence of any residual tumor tissue or inflammatory signs. We believe that the approach described in this paper allows juxta-articular osteoid osteomas to be accessed in a minimally invasive manner and permits not only adequate resection but also the treatment of chondral lesions that could remain after tumor resection. PMID- 26545942 TI - Arthroscopic treatment of acute acromioclavicular dislocations using a double button device: Clinical and MRI results. AB - INTRODUCTION: Arthroscopic treatment of acute grade 3 and 4 acromioclavicular dislocation is controversial, due to the risk of recurrence and of postoperative reduction defect. The purpose of the present study was to investigate whether the healing of the acromioclavicular (AC) and coracoclavicular (CC) ligaments and the accurate 3D positioning parameters of the AC joint using MRI were correlated with satisfactory functional outcome. MATERIAL: Thirty-nine patients were enrolled from 2009 to 2011 and managed arthroscopically by CC lacing using a double-button device. METHODS: Clinical assessment included the Shoulder and Hand (QuickDash) score, Constant-Murley score and visual analog scale (VAS) for residual pain. Time and rate to return to work and return to sport were assessed according to type of sport and work. Postoperative complications were recorded. Radiological examination consisted of anteroposterior clavicle and lateral axillary radiographs. AC ligament healing and 3D joint congruency were assessed on MRI and correlated to the clinical results. RESULTS: Mean patient age was 35.7 years (range, 20-55). Mean follow-up was 42.3+/-10.6 months (range, 24-60). At final follow-up, mean QuickDash score, Constant score and VAS were respectively 1.7+/-4 (range, 0-11), 94.7+/-7.3 (range, 82-100) and 0.5+/-1.4 (range, 0-2). Thirty-five (90%) patients were able to resume work, including heavy manual labor, and sport. Radiology found accurate 3D joint congruency in 34 patients (87%) and CC and AC ligament healing in 36 (93%). Complications included reduction loss at 6 weeks in 3 patients, requiring surgical stabilization. Satisfactory functional results were associated with accurate AC joint congruency in the coronal and axial planes (P<0.05) and good AC and CC ligament healing (P<0.04). An initial 25% reduction defect in the coronal plane was not associated with poor functional results (P=0.07). CONCLUSION: Arthroscopic treatment by CC lacing satisfactorily restored ligament and joint anatomy in the present series. These satisfactory anatomic results correlated with good clinical outcome encourage continuing with this technique. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26545943 TI - External bone remodeling after injectable calcium-phosphate cement in benign bone tumor: two cases in the hand. AB - Bone remodeling commonly occurred after fracture and curettage benign bone tumor. A lot of previous articles reported "internal" trabecular bone remodeling. There were no previous clinical reports about "external" cortical bone remodeling. We present here 2 clinical cases of "external" bone remodeling after injectable calcium-phosphate in benign bone tumor in the hand. In two cases of benign bone tumor, we performed complete removal of the tumor and immediate filling of the metacarpal bone with injectable calcium-phosphate cement Arexbone((r)) from the mechanical viewpoint. With respect to the shape of the calcium-phosphate, by using an injection-type, calcium-phosphate is adhered uniformly to the bone cortex by injecting, remodeling has been promoted. After 5 and 8years, both cases were no recurrences, and the shape of the metacarpal looked close to the contralateral side. These findings supposed to be concerned with potential self healing and self-protection mechanism in human body. PMID- 26545944 TI - Complication rates and types of failure after arthroscopic acute acromioclavicular dislocation fixation. Prospective multicenter study of 116 cases. AB - AIMS: To report and analyze both the surgical and radiographic complications associated with anatomic coracoclavicular (CC) ligament procedures and to evaluate the effect of these complications on patient outcomes. PATIENTS AND METHODS: From July 2012 to July 2013, 116 primary anatomic CC ligament procedures (all arthroscopic endobutton fixations) were performed in 14 different centers. Demographic, surgical, subjective, and radiographic data were prospectively analyzed in 14 centers with a minimum follow-up of 12 months. RESULTS: This series included 96 men and 20 women, mean age 37 years old, with a mean delay to surgery of 10 days. No intraoperative complications were reported. There were 11 complications due to hardware failure resulting in a loss of reduction, 1 coracoid fracture, 7 cases of adhesive capsulitis, 2 local infections, 5 cases of hardware pain. There were significant differences in outcomes between patients who did and did not develop complications: mean CS=71 vs. 93, (P<0.0001). All the parameters of the CS were statistically affected (P<0.0001). Forty-eight patients had persistent dislocation>150% on an AP X-ray which affected the pain and activity CS (P=0.023 and P=0.044). No preoperative predictive factors were identified. These patients could not return to the same level of sports activities due to persistent pain. DISCUSSION: Anatomic procedures to treat AC joint dislocation using CC ligament reconstruction resulted in an overall complication rate of 22.4% and influenced the return to sports. Good to excellent outcomes were reported in patients without complications. CLINICAL SERIES: Level of evidence 4. PMID- 26545945 TI - Evaluation of a triplex real-time PCR system to detect the plant-pathogenic molds Alternaria spp., Fusarium spp. and C. purpurea. AB - This article describes the development of a triplex real-time PCR system for the simultaneous detection of three major plant-pathogenic mold genera (Alternaria spp., Fusarium spp. and the species Claviceps purpurea). The designed genus specific primer-probe systems were validated for sensitivity, specificity and amplification in the presence of background DNA. PMID- 26545947 TI - [Role of rifaximin in the treatment of hepatic encephalopathy]. AB - Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence. PMID- 26545946 TI - Meis2 is essential for cranial and cardiac neural crest development. AB - BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2alpha-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse. PMID- 26545948 TI - Lower gastrointestinal bleeding as a presentation of miliary tuberculosis. PMID- 26545949 TI - [A comparison of medical versus surgical treatment in Barrett's esophagus acid control]. AB - INTRODUCTION: Barrett's oesophagus (BE) is an oesophageal injury caused by gastroesophageal acid reflux. One of the main aims of treatment in BE is to achieve adequate acid reflux control. OBJECTIVE: To assess acid reflux control in patients with BE based on the therapy employed: medical or surgical. METHODS: A retrospective study was performed in patients with an endoscopic and histological diagnosis of BE. Medical therapy with proton pump inhibitors (PPI) was compared with surgical treatment (Nissen fundoplication). Epidemiological data and the results of pH monitoring (pH time <4, prolonged reflux >5min, DeMeester score) were evaluated in each group. Treatment failure was defined as a pH lower than 4 for more than 5% of the recording time. RESULTS: A total of 128 patients with BE were included (75 PPI-treated and 53 surgically-treated patients). Patients included in the two comparison groups were homogeneous in terms of demographic characteristics. DeMeester scores, fraction of time pH<4 and the number of prolonged refluxes were significantly lower in patients with fundoplication versus those receiving PPIs (P<.001). Treatment failure occurred in 29% of patients and was significantly higher in those receiving medical therapy (40% vs 13%; P<.001). CONCLUSIONS: Treatment results were significantly worse with medical treatment than with anti-reflux surgery and should be optimized to improve acid reflux control in BE. Additional evidence is needed to fully elucidate the utility of PPI in this disease. PMID- 26545950 TI - [Silodosin: An overlooked cause of drug-induced diarrhea]. PMID- 26545951 TI - [Cholecysto-cutaneous fistula and cholecysto-choledochal fistula (Mirizzi II)]. PMID- 26545952 TI - Optical coherence microscopy of living cells and bioengineered tissue dynamics in high-resolution cross-section. AB - Optical coherence tomography (OCT) is a valuable tool in the cross-sectional observation/analysis of three-dimensional (3-D) biological tissues, and that histological observation is important clinically. However, the resolution of the technology is approximately 10-20 MUm. In this study, optical coherence microscopy (OCM), a tomographic system combining OCT technology with a microscopic technique, was constructed for observing cells individually with a resolution at the submicrometer level. Cells and 3-D tissues fabricated by cell sheet technology were observed by OCM. Importantly, the cell nuclei and cytoplasm could be clearly distinguished, and the time-dependent dynamics of cell-sheet tissues could be observed in detail. Additionally, the 3-D migration of cells in the bioengineered tissue was also detected using OCM and metal-labeled cells. Bovine aortic endothelial cells, but not NIH3T3 murine embryonic skin fibroblasts, actively migrated within the 3-D tissues. This study showed that the OCM system would be a valuable tool in the fields of cell biology, tissue engineering, and regenerative medicine. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 481-488, 2017. PMID- 26545953 TI - Exposure to double-stranded RNA mediated by tobacco rattle virus leads to transcription up-regulation of effector gene Mi-vap-2 from Meloidogyne incognita and promotion of pathogenicity in progeny. AB - Meloidogyne spp. are economically important plant parasites and cause enormous damage to agriculture world-wide. These nematodes use secreted effectors which modify host cells, allowing them to obtain the nutrients required for growth and development. A better understanding of the roles of effectors in nematode parasitism is critical for understanding the mechanisms of nematode-host interactions. In this study, Mi-vap-2 of Meloidogyne incognita, a gene encoding a venom allergen-like protein, was targeted by RNA interference mediated by the tobacco rattle virus. Unexpectedly, compared with a wild type line, a substantial up-regulation of Mi-vap-2 transcript was observed in juveniles collected at 7 days p.i. from Nicotiana benthamiana agroinfiltrated with TRV::vap-2. This up regulation of the targeted transcript did not impact development of females or the production of galls, nor the number of females on the TRV::vap-2 line. In a positive control line, the transcript of Mi16D10 was knocked down in juveniles from the TRV::16D10 line at 7 days p.i., resulting in a significant inhibition of nematode development. The up-regulation of Mi-vap-2 triggered by TRV-RNAi was inherited by the progeny of the nematodes exposed to double-stranded RNA. Meanwhile, a substantial increase in Mi-VAP-2 expression in those juvenile progeny was revealed by ELISA. This caused an increase in the number of galls (71.2%) and females (84.6%) produced on seedlings of N. benthamiana compared with the numbers produced by control nematodes. Up-regulation of Mi-vap-2 and its encoded protein therefore enhanced pathogenicity of the nematodes, suggesting that Mi-vap-2 may be required for successful parasitism during the early parasitic stage of M. incognita. PMID- 26545954 TI - Nanostructured Ni2 P as a Robust Catalyst for the Hydrolytic Dehydrogenation of Ammonia-Borane. AB - Ammonia-borane (AB) is a promising chemical hydrogen-storage material. However, the development of real-time, efficient, controllable, and safe methods for hydrogen release under mild conditions is a challenge in the large-scale use of hydrogen as a long-term solution for future energy security. A new class of low cost catalytic system is presented that uses nanostructured Ni2 P as catalyst, which exhibits excellent catalytic activity and high sustainability toward hydrolysis of ammonia-borane with the initial turnover frequency of 40.4 mol(H2) mol(Ni2P) (-1) min(-1) under air atmosphere and at ambient temperature. This value is higher than those reported for noble-metal-free catalysts, and the obtained Arrhenius activation energy (Ea =44.6 kJ mol(-1) ) for the hydrolysis reaction is comparable to Ru-based bimetallic catalysts. A clearly mechanistic analysis of the hydrolytic reaction of AB based on experimental results and a density functional theory calculation is presented. PMID- 26545955 TI - Prevalence of sexual dysfunction after risk-reducing salpingo-oophorectomy. AB - OBJECTIVES: To determine the prevalence of sexual dysfunction in women after risk reducing salpingo-oophorectomy (RRSO) and to assess factors which may influence sexual wellbeing following this procedure. METHODS: This work is a cross sectional study of women who underwent RRSO at a tertiary gynecologic oncology unit between January 2009 and October 2014. Data collection involved a comprehensive questionnaire including validated measures of sexual function, sexual distress, relationship satisfaction, body image, impact of event, menopause specific quality of life, and general quality of life. Participants were invited to undergo blood testing for serum testosterone and free androgen index (FAI). RESULTS: 119 of the 206 eligible women participated (58%), with a mean age of 52years. The prevalence of female sexual dysfunction (FSD) was 74% and the prevalence of hypoactive sexual desire disorder (HSDD) was 73%. Common sexual issues experienced included; lubrication difficulty (44%), reduced sexual satisfaction (41%), dyspareunia (28%) and orgasm difficulty (25%). Relationship satisfaction, the use of topical vaginal estrogen and lower generalized body pain were significantly associated with a decreased likelihood of sexual dysfunction. Serum testosterone, FAI, the use of systemic hormone replacement therapy (HRT), prior history of breast cancer, menopausal status at the time of surgery and hysterectomy did not correlate with sexual dysfunction. CONCLUSION: The prevalence of FSD and HSDD after RRSO was 74% and 73% respectively. Relationship satisfaction, low bodily pain and use of topical vaginal estrogen were associated with a lower likelihood of sexual dysfunction. There was no correlation between serum testosterone or FAI, and sexual dysfunction. PMID- 26545956 TI - Reply to letters to the editor concerning the article "The effect of cloth stoma covers on tracheal climate of laryngectomy patients". PMID- 26545957 TI - Potassium 4,5-Bis(dinitromethyl)furoxanate: A Green Primary Explosive with a Positive Oxygen Balance. AB - Potassium 4,5-bis(dinitromethyl)furoxanate was synthesized readily from cyanoacetic acid. It was characterized by IR spectroscopy, elemental analysis, NMR spectroscopy, and differential scanning calorimetry (DSC), and the structure was confirmed by X-ray single-crystal diffraction. Its positive oxygen balance, high density (2.130 g cm(-3)), sensitivity (IS=2 J, FS=5 N), and calculated heat of formation (-421.0 kJ mol(-1)), combined with its calculated superior detonation performance (D=7759.0 m s(-1), P=27.3 GPa), make it a competitive replacement as a green primary explosive. PMID- 26545958 TI - Progressive paralyzing sciatica revealing a pelvic pseudoaneurysm a year after hip surgery in a 12yo boy. AB - Identifying extra spinal causes of a lumbar radiculopathy or polyneuropathy can be a tricky diagnosis challenge, especially in children. Among them, traumatic or iatrogenic pseudoaneurysms of iliac arteries have been seldom reported, in adults' series. The authors report an unusual case of progressive paralyzing left sciatica and lumbar plexopathy in a 12 years old boy, 12 months after a pelvic osteotomy for bilateral hip luxation secondary to osteochondritis dissecans. Spine MRI and pelvic CT angiography revealed a giant internal iliac artery pseudoaneurysm, enclosed in a chronic hematoma. The patient was successfully treated with endovascular coil embolization, and subsequent surgical hematoma evacuation. However, three months after treatment, neurological recovery was incomplete. This case highlights the importance of a rapid and extensive diagnosis work up of all causes of lower limb radiculopathies in children, including pelvic arteries lesions especially after pelvic surgery to avoid therapeutic delays that may jeopardize the chances of neurological recovery. PMID- 26545959 TI - Functioning of the three attentional networks and vigilance in primary insomnia. AB - BACKGROUND: Results from cognitive measures in primary insomnia (PI) patients are not consistent with the difficulties in performing daily living tasks of which these patients complain about. Lack of sensitivity of the tests and the data concerning some cognitive functions may explain this discordance. The aim of the present investigation was to better characterize cognitive deficits of PI patients in order to further understand their cognitive complaints. We looked at attentional and executive function because of their high involvement in daily living tasks. METHODS: A total of 21 PI patients and 16 good sleepers completed the Attentional Network Test (ANT). We only included untreated PI patients since sleep medication could be a confounding factor when assessing cognition. RESULTS: While PI patients, compared to good sleepers, were found to have a longer overall reaction time (RT) and perform more slowly in the incongruent flanker condition (ie, conflict situation) than in the congruent condition, no group effects were observed for the variables representing the three attentional networks (ie, alerting, orienting, and executive functions). CONCLUSIONS: The present study revealed a conflict resolution deficit in untreated PI patients. This impairment may be linked to the prefrontal alterations reported in neuroimaging studies in these patients. Patients had also an impaired vigilance compared to good sleepers, likely due to the high cognitive load of the ANT. These results would serve to explain the complaints of PI patients about difficulties performing daily living tasks that are demanding and of long duration. PMID- 26545960 TI - Inferior vena cava web causing Budd-Chiari syndrome. PMID- 26545961 TI - Autophagy, which is decreased in labouring fetal membranes, regulates IL-1beta production via the inflammasome. AB - INTRODUCTION: IL-1beta plays a vital role in the terminal processes of human labour and delivery. Inflammasome activation is required to process pro IL-1beta to an active, secreted molecule. Recent studies have shown that autophagy regulates IL-1beta via the inflammasome. The aims were to determine the effect of (i) human spontaneous term and preterm labour on the expression of autophagy proteins in fetal membranes; and (ii) autophagy inhibition on IL-1beta release. METHODS: Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women. Tissue explants were used to determine the effect of inhibition of autophagy on IL-1beta secretion. RESULTS: Expression of the autophagy proteins Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg16L1 were lower after spontaneous term labour. Beclin-1 and Atg7 expression were lower after spontaneous preterm labour. Beclin-1, Atg3, and Atg7 expression were lower after preterm pre-labour rupture of membranes (PPROM) compared to preterm with intact membranes. LC3B-I expression was higher after spontaneous term and preterm labour and with PPROM; there was no difference in LC3B-II expression between the two groups. The autophagy inhibitor LY290042 increased IL-1beta secretion in the presence of bacterial endotoxin LPS; IL-1beta secretion was ameliorated in the presence inflammasome inhibitors. DISCUSSION: Autophagy is decreased in fetal membranes after spontaneous labour and delivery, and PPROM. Inhibition of autophagy regulates the secretion of IL-1beta via inflammasome activation. IL 1beta is a major contributor to the pathophysiology of spontaneous preterm birth. Therefore activation of autophagy may be a potential therapeutic mechanism to delay or prevent infection-induced preterm birth. PMID- 26545962 TI - Differentiation of first trimester cytotrophoblast to extravillous trophoblast involves an epithelial-mesenchymal transition. AB - The transformation of cytotrophoblast (CTB) to extravillous trophoblast (EVT) is an essential process for placental implantation. EVT generated at the tips of the anchoring villi migrate away from the placenta and invade the endometrium and maternal spiral arteries, where they modulate maternal immune responses and remodel the arteries into high-volume conduits to facilitate uteroplacental blood flow. The process of EVT differentiation has several factors in common with the epithelial-to-mesenchymal transition (EMT) observed in embryonic development, wound healing and cancer metastasis. We hypothesized that the generation of invasive EVT from CTB was a form of EMT. We isolated paired CTB and EVT from first trimester placentae, and compared their gene expression using a PCR array comprising probes for genes involved in EMT. Out of 84 genes, 24 were down regulated in EVT compared to CTB, including epithelial markers such as E-cadherin (-11-fold) and occludin (-75-fold). Another 30 genes were up-regulated in EVT compared to CTB including mesenchymal markers such as vimentin (235-fold) and fibronectin (107-fold) as well as the matrix metalloproteinases, MMP2 and MMP9 (357-fold, 129-fold). These alterations also included major increases in the ZEB2 (zinc finger E-box binding homeobox 2, 198-fold) and TCF4 (transcription factor 4, 18-fold) transcription factors, suggesting possible stimulatory mechanisms. There was substantial up-regulation of the genes encoding TGFbeta1 and TGFbeta2 (48-fold, 115-fold), which may contribute to the maintenance of the mesenchymal like phenotype. We conclude that transformation of CTB to EVT is consistent with an EMT, although the differences with other types of EMT suggest this may be a unique form. PMID- 26545963 TI - The sex ratio at birth in South Africa increased 9months after the 2010 FIFA World Cup. AB - INTRODUCTION: In humans in the absence of significant stress the sex ratio at birth [males/(males+females)] is in favor of more male than female live births. METHODS: This study sought to determine the influence of the 2010 Federation Internationale de Football Association (FIFA) World Cup in South Africa on the sex ratio at birth in that country specifically 9months afterwards. Publicly available data from Statistics South Africa was utilized detailing recorded live births. Analysis was carried out by Chi-squared tests. RESULTS: February and March 2011 about 9months after the World Cup, had the highest observed sex ratio at birth (relatively more male births) of 0.5063 for the period 2003 to 2012. The observed sex ratio at birth in the considered two months of 2011 was 0.63% (p=0.02) greater than the sex ratio at birth for corresponding periods from 2008 to 2012. The increase noted in 2011 corresponds to more than 1000 extra male births than expected for February and March 2011. CONCLUSION: The 2010 FIFA World Cup was followed about 9months afterwards by a significant increase in the sex ratio at birth. The main mechanism driving the observed increase in the sex ratio at birth in South Africa is most likely more frequent sexual intercourse at population level during the tournament. PMID- 26545964 TI - 1H NMR metabolic profiling of cod (Gadus morhua) larvae: potential effects of temperature and diet composition during early developmental stages. AB - Marine aquaculture offers a great source of protein for the increasing human population, and farming of, for example, Atlantic salmon is a global industry. Atlantic cod farming however, is an example of a promising industry where the potential is not yet realized. Research has revealed that a major bottleneck to successful farming of cod is poor quality of the larvae and juveniles. A large research program was designed to increase our understanding of how environmental factors such as temperature and nutrition affects cod larvae development. Data on larvae growth and development were used together with nuclear magnetic resonance. The NMR data indicated that the temperature influenced the metabolome of the larvae; differences were related to osmolytes such as betaine/TMAO, the amino acid taurine, and creatine and lactate which reflect muscle activity. The larvae were fed Artemia from stage 2, and this was probably reflected in a high taurine content of older larvae. Larvae fed with copepods in the nutrition experiment also displayed a high taurine content, together with higher creatine and betaine/TMAO content. Data on the cod larvae metabolome should be coupled to data on gene expression, in order to identify events which are regulated on the genetic level versus regulation resulting from temperature or nutrition during development, to fully understand how the environment affects larval development. PMID- 26545965 TI - N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons. AB - Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3) that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N docosahexaenoylethanolamine), an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1) transcription and sonic hedgehog (Shh) target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO) agonist (SAG) or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway. PMID- 26545966 TI - Discussion. PMID- 26545968 TI - Neoaortic support hose. PMID- 26545967 TI - Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences. AB - OBJECTIVES: We review differences in the incidence and timing of adverse events in patients implanted with continuous-flow left ventricular assist devices (LVADs), using the Mechanical Circulatory Support Research Network registry. METHODS: From May 2004 to September 2014, a total of 734 patients (591 men; median age: 59 years) underwent primary continuous-flow LVAD implantation at our institutions. Patients implanted with the HeartMate II (HMII) (560 [76%] patients), compared with the HeartWare ventricular assist device (HVAD; 174 [24%]) were more often receiving destination therapy (47% vs 20%; P < .01), had a lower preoperative creatinine level (1.2 vs 1.3; P = .01), and had less median preoperative right ventricular dysfunction (mild vs moderate; P < .01). Ischemic etiology, prior sternotomy, and median INTERMACS profile were similar. RESULTS: Overall mortality was 54 of 734 (7.4%); 41 of 560 (7.3%) in the HMII group, and 13 of 174 (7.5%) in the HVAD group (P = .95). Follow-up was available in 100% of early survivors for a median of 1 year (max: 10 years) and a total of 1120 patient-years of support (HMII: 940 patient-years [median: 1.1 years, max: 5.3 years] and HVAD: 180 patient-years [median: 0.6 year, max: 10.4 years]). On multivariable analysis, GI bleeding (P = .63), any infection (P = .32), driveline infection (P = .10), and pump thrombus (P = .64) were similar between devices while HeartWare HVAD was associated with higher risk of stroke (HR: 1.8, [1.25, 2.5], P = .003). CONCLUSIONS: In this pooled analysis, a trend was found for higher incidence of percutaneous driveline infections in patients treated with the HMII; a higher incidence of stroke and time-related cumulative risk of any infection and stroke was found in patients treated with the HVAD, which was independently associated with higher stroke risk. PMID- 26545969 TI - Discussion. PMID- 26545970 TI - What is a "good" result after transcatheter mitral repair? Impact of 2+ residual mitral regurgitation. AB - OBJECTIVE: The study objective was to assess the impact on follow-up outcomes of residual mitral regurgitation 2+ in comparison with <= 1+ after MitraClip (Abbott Vascular Inc, Santa Clara, Calif) repair. METHODS: We compared the outcomes of mitral regurgitation 2+ and mitral regurgitation <= 1 + groups among a population of 223 consecutive patients with acute residual mitral regurgitation <= 2+ who underwent MitraClip implantation at San Raffaele Scientific Institute (Milan, Italy) between October 2008 and December 2014. RESULTS: Residual mitral regurgitation 2+ was found in 64 patients (28.7%). Overall actuarial survival was 63.1% +/- 4.4% at 48 months. Cumulative incidence functions of cardiac death in patients with mitral regurgitation 2+ was significantly higher (Gray test P < .001) compared with the mitral regurgitation <= 1+ group. The adjusted hazard ratio was 5.28 (95% confidence interval, 2.41-11.56, P < .001). Cumulative incidence function of mitral regurgitation >= 3+ recurrence in patients with residual mitral regurgitation <= 1+ and mitral regurgitation 2+ at 48 months was 13.3% +/- 3.8% and 45.2% +/- 6.8%, respectively (Gray test P < .001). Multivariate model showed that mitral regurgitation 2+ was the only factor associated with the development of mitral regurgitation >= 3+ at follow-up (adjusted hazard ratio, 6.71; 95% confidence interval, 3.48-12.90; P < .001). Mitral regurgitation cause was not associated with cardiac death and recurrence of mitral regurgitation >= 3+ at follow-up. No relationship between New York Heart Association class and follow-up time after MitraClip implant was found (odds ratio, 1.07; 95% confidence interval, 0.98-1.15; P = .11), and factors related to postoperative New York Heart Association also included residual mitral regurgitation 2+ (P = .07). CONCLUSIONS: Residual 2+ mitral regurgitation after MitraClip implantation was associated with worse follow-up outcomes compared with <= 1+ mitral regurgitation, including survival, symptom relief, and mitral regurgitation recurrence. Better efficacy should be pursued by transcatheter mitral repair technologies. PMID- 26545972 TI - Congenital Heart Disease and Primary Ciliary Dyskinesia. AB - Through the better understanding of the genetics and clinical associations of Primary Ciliary Dyskinesia (PCD), an autosomal recessive disorder of ciliary motility and mucociliary clearance, the association between PCD and heterotaxic congenital heart disease (CHD) has been established. In parallel, research into the cause of CHD has elucidated further the role of ciliary function on the development of normal cardiovascular structure. Increased awareness by clinicians regarding this elevated risk of PCD in patients with CHD will allow for more comprehensive screening and identification of cases in this high-risk group with earlier diagnosis leading to improved health outcomes. PMID- 26545971 TI - Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery. AB - OBJECTIVE: Antibiotic use, particularly type and duration, is a crucial modifiable risk factor for Clostridium difficile. Cardiac surgery is of particular interest because prophylactic antibiotics are recommended for 48 hours or less (vs <=24 hours for noncardiac surgery), with increasing vancomycin use. We aimed to study associations between antibiotic prophylaxis (duration/vancomycin use) and C difficile among patients undergoing coronary artery bypass grafting. METHODS: We extracted data on coronary artery bypass grafting procedures from the national Premier Perspective claims database (2006 2013, n = 154,200, 233 hospitals). Multilevel multivariable logistic regressions measured associations between (1) duration (<2 days, "standard" vs >=2 days, "extended") and (2) type of antibiotic used ("cephalosporin," "cephalosporin + vancomycin," "vancomycin") and C difficile as outcome. RESULTS: Overall C difficile prevalence was 0.21% (n = 329). Most patients (59.7%) received a cephalosporin only; in 33.1% vancomycin was added, whereas 7.2% received vancomycin only. Extended prophylaxis was used in 20.9%. In adjusted analyses, extended prophylaxis (vs standard) was associated with significantly increased C difficile risk (odds ratio, 1.43; confidence interval, 1.07-1.92), whereas no significant associations existed for vancomycin use as adjuvant or primary prophylactic compared with the use of cephalosporins (odds ratio, 1.21; confidence interval, 0.92-1.60, and odds ratio, 1.39; confidence interval, 0.94 2.05, respectively). Substantial inter-hospital variation exists in the percentage of extended antibiotic prophylaxis (interquartile range, 2.5-35.7), use of adjuvant vancomycin (interquartile range, 4.2-61.1), and vancomycin alone (interquartile range, 2.3-10.4). CONCLUSIONS: Although extended use of antibiotic prophylaxis was associated with increased C difficile risk after coronary artery bypass grafting, vancomycin use was not. The observed hospital variation in antibiotic prophylaxis practices suggests great potential for efforts aimed at standardizing practices that subsequently could reduce C difficile risk. PMID- 26545973 TI - The effect of FT500 Plus((r)) on ovarian stimulation in PCOS women. AB - Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus((r))). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5 month follow-up in the Group A (11.1+/-0.9 versus 13.5+/-1; P=0.0001). Group A showed a significant increase in the number of MII oocytes (6.3+/-2.5 versus 4.5+/-2; P=0.03) and glutathione peroxidase activity in follicular fluid (15.4+/ 6.2 versus 11+/-2.2; P=0.04). FT500 Plus((r)) may be considered in PCOS patient for improving oocyte quality. PMID- 26545974 TI - Potential seminal transport of pharmaceuticals to the conceptus. AB - Small molecule pharmaceutical products are assumed to reach concentrations in semen similar to those in blood plasma. Exposure modeling for these small molecule products in humans assumes a daily dose of 5mL of semen and 100% absorption from the vagina with distribution to the conceptus through the maternal systemic circulation. Monoclonal antibody drugs are present in semen at concentrations about 2% or less of those in blood, and the modeling used for small molecules will over-estimate the possibility of conceptus exposure to immunoglobulins. It is not known whether peptide products reach semen, but in general peptide medications are destroyed by vaginal peptidases, and conceptus exposure is predicted to be minimal. Theoretical exposure routes to pharmaceuticals that might result in exposure of the conceptus greater than that of maternal systemic exposures include direct access through the cervical canal, adsorption to sperm for carriage into the oocyte, and direct delivery from the vaginal veins or lymphatics to the uterine artery. There is some evidence for direct access to the uterus for progesterone, terbutaline, and danazol, but the evidence does not involve exposures during pregnancy in most instances. Studies in mice, rats, rabbits, and monkeys do not suggest that exposure to small molecule pharmaceuticals in semen imposes risks to the conceptus beyond those that can be predicted using modeling of systemic maternal exposure. Monoclonal antibody and peptide exposure in semen does not pose a significant risk to the conceptus. PMID- 26545975 TI - Factors influencing acceptability of voluntary HIV testing among pregnant women in Gamboma, Republic of Congo. AB - BACKGROUND: This study was carried out to identify factors affecting the acceptability of voluntary HIV testing among pregnant women in a semi-rural city, Gamboma, Republic of Congo. METHODS: A cross-sectional study was conducted between January and September 2012. Pregnant women attending antenatal heath care at an integrated health center were enrolled after informed consent and followed through voluntary HIV testing. RESULTS: Among 136 participants, 98 women (72 %) accepted voluntary HIV testing after pre-test counseling. Women with basic education, those who cited blood transfusion as a mode of transmission and prevention of mother-to-child transmission (MTCT) were more likely to accept testing as well those informed about free HIV testing. Interestingly, pregnant women who had heard about HIV/AIDS from hospital setting were less likely to accept testing. CONCLUSIONS: Our data indicate that increasing general education on HIV transmission/prevention modes is crucial for increasing acceptability of screening. Furthermore, HIV/AIDS knowledge disseminated to patients in hospital settings should be carefully monitored. Lastly, scaling-up MTCT services along with a better and larger community information, may address accessibility barriers observed in the present study. PMID- 26545976 TI - Local audit: How tightly should we police antibiotic prescribing for urinary tract infection and how should we modify national policy? AB - OBJECTIVE: In 2010, our hospital, in line with National guidance, changed advice on antibiotic prescribing for UTI to reduce use of cephalosporins in favour of penicillins. We hypothesized that this change in policy would have no impact on the pattern of antibiotic resistance of the organisms causing UTI. STUDY DESIGN: Audit review of all urine samples sent to BWH from 2009 to 2013 and positive cultures showing Enterobacteriaceae were then tested for antibiotic susceptibility. RESULTS: There has been an increase in the resistance of both Co amoxiclav and Ciprofloxacin since 2009. Co-amoxiclav and trimethoprim now have similar resistance rates. Ciprofloxacin resistance has risen fairly quickly in the last four years from 1% to 8%. Resistance to nitrofurantoin has remained low. Gentamicin resistance remained stable and very low, second best to meroponem. IMPACT: The results have been fed back to commissioners and internally and are being used as part of the guideline updating process. CONCLUSIONS: Hospital protocols for treating infections should be reviewed and updated based on accurate local data. These data should be used for formulating regional specific protocols. Our results suggest that meroponem and ciprofloxacin should be reserved for microbiologically proven resistance to other antibiotics. PMID- 26545977 TI - Plakoglobin expression in fibroblasts and its role in idiopathic pulmonary fibrosis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial fibrotic lung disease of unknown origin and without effective therapy characterized by deposition of extracellular matrix by activated fibroblasts in the lung. Fibroblast activation in IPF is associated with Wnt/beta-catenin signaling, but little is known about the role of the beta-catenin-homologous desmosomal protein, plakoglobin (PG), in IPF. The objective of this study was to assess the functional role of PG in human lung fibroblasts in IPF. METHODS: Human lung fibroblasts from normal or IPF patients were transfected with siRNA targeting PG and used to assess cellular adhesion to a fibronectin substrate, apoptosis and proliferation. Statistical analysis was performed using Student's t-test with Mann-Whitney post-hoc analyses and results were considered significant when p < 0.05. RESULTS: We found that IPF lung fibroblasts expressed less PG protein than control fibroblasts, but that characteristic fibroblast phenotypes (adhesion, proliferation, and apoptosis) were not controlled by PG expression. Consistent with this, normal fibroblasts in which PG was silenced displayed no change in functional phenotype. CONCLUSIONS: We conclude that diminished PG levels in IPF lung fibroblasts do not directly affect certain phenotypic behaviors. Further study is needed to identify the functional consequences of decreased PG in these cells. PMID- 26545978 TI - Characteristics and severity of asthma in children with and without atopic conditions: a cross-sectional study. AB - BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions. METHODS: For this cross-sectional study, 703 children (ages 4 to 12 years) from the PACMAN cohort study were selected. All of the children were regular users of asthma medication. The study population was divided into nine subgroups according to parental-reported allergies of the child (hay fever, eczema, food allergy or combinations of these). In order to assess whether these subgroups differed clinically, the groups were compared for child characteristics (age, gender, family history of asthma), asthma exacerbations in the past year (oral corticosteroids (OCS) use; asthma-related emergency department (ED) visits), asthma control, fractional exhaled nitric oxide level (FeNO), and antihistaminic usage. RESULTS: In our study, 79.0% of the parents reported that their child suffered from at least one atopic condition (hay fever, food allergy and eczema), and one quarter of the parents (25.6%) reported that their child suffered from all three atopic conditions. Having more than one atopic condition was associated with an increased risk of OCS use (OR = 3.3, 95% CI = 1.6 - 6.6), ED visits (OR = 2.3, 95% CI = 1.2 - 4.6) in the past year and inadequate short term asthma control (OR = 1.9, 95% CI = 1.3 - 2.8). CONCLUSIONS: Children who use asthma medication often also have other allergic conditions. Parental reported allergies were associated with a higher risk of more severe asthma (more asthma complaints and more asthma exacerbations). PMID- 26545979 TI - Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report. AB - BACKGROUND: Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. CASE PRESENTATION: We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. CONCLUSION: Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism. PMID- 26545981 TI - Mouse hippocampal phosphorylation footprint induced by generalized seizures: Focus on ERK, mTORC1 and Akt/GSK-3 pathways. AB - Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated hippocampal activity. The results reported in the present study are reminiscent of the one observed in other models of generalized seizures, thus defining a common molecular footprint induced by intense and aberrant hippocampal activities. PMID- 26545980 TI - The outcome and prognostic factors for lymph node recurrence after node-sparing definitive external beam radiotherapy for localized prostate cancer. AB - BACKGROUND: The prognostic factors for the recurrence of lymph node (LN) metastasis after dose-escalated radiotherapy (RT) in prostate cancer patients have not been well investigated. We report the prognostic factors and outcomes in patients receiving salvage treatment for LN recurrence after high-dose intensity modulated RT (IMRT). METHODS: We studied a cohort of 419 patients with localized prostate adenocarcinoma undergoing definitive IMRT (78 Gy). LN recurrence was diagnosed by size criteria using computed tomography (CT) or magnetic resonance imaging, or abnormal uptake of (18)F-fluorocholine by LNs on positron emission tomography/CT. Overall survival and LN recurrence-free survival (LNRFS) were calculated, and prognostic factors were evaluated. RESULTS: With a median follow up of 60 months, 18 patients (4.3 %) had LN recurrence and a significantly lower 5-year overall survival rate (60 vs. 90 %, p = 0.003). Univariate analysis showed that T3/T4 stage (p = 0.003), Gleason score >7 (p < 0.001), and estimated risk of pelvic LN involvement of >30 % by the Roach formula (p = 0.029) were associated with significantly lower LNRFS. On multivariate analysis, high Gleason score (hazard ratio = 5.99, p = 0.007) was the only independent factor. The 1/2-year overall survivals after LN recurrence were 67/54 %. Patients with isolated LN recurrence (p = 0.003), prostate-specific antigen (PSA) doubling time >5 months (p = 0.009), interval between PSA nadir and biochemical failure >12 months (p = 0.035), and PSA <10 ng/ml at LN recurrence (p = 0.003) had significantly better survival. Patients with isolated LN recurrence had significantly better survival when treated with combined RT and hormones than when treated with hormones alone (p = 0.011). CONCLUSIONS: Gleason score of >7 may predict LN recurrence in prostate cancer patients treated with definitive IMRT. Small number of patients limits the extrapolation of this risk with the primary treatment strategy. Combined RT and hormones may prolong survival in patients with isolated LN recurrence. PMID- 26545982 TI - BMSCs transplantation improves cognitive impairment via up-regulation of hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. AB - Bone marrow mesenchymal stem cells (BMSCs) transplantation can ameliorate cognitive impairment in chronic ischemic brain injury, but the underlying mechanism is poorly understood. It is considered that the hippocampus holds the capabilities of memory consolidation and spatial navigation, and the gamma amino butyric acid (GABA)ergic system plays an important role in the control of learning and memory processes. Herein, we investigated whether transplantation of BMSCs could improve cognitive impairment via regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Animals treated with permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) (a rat model of chronic cerebral hypoperfusion) received intravenous injections of BMSCs or saline as experimental group and control group I, the sham-operated rats received intravenous injections of BMSCs or saline as the sham group and control group II. Four weeks later, the Morris Water Maze was employed to evaluate the cognitive changes of each group, immunohistochemistry and western blotting was used to investigate the GABAergic system expression including GABA, glutamic acid decarboxylase 67 (GAD67) or GABA(B) receptor 1 (GABA(B)R1) in the hippocampus. Our results showed that the 2VO model presented decreased capacities of learning and memory and down-regulated the expression of GABA, GAD67 or GABA(B)R1 in the hippocampal CA1 subfield in comparison to the sham group (P<0.05), while administration of BMSCs (experimental group) manifested increased performances of learning sessions and probe tasks, as well as up-regulated expression of GABA, GAD67 or GABA(B)R1 compared with the control group I (P<0.05). Collectively, these findings suggest that transplantation of BMSCs is capable of improving cognitive impairment via up-regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Hence, BMSCs transplantation could serve as an important tool for cell therapy in chronic cerebral hypoperfusion disorders. PMID- 26545984 TI - How Tom Moon's research highlighted the question of glucose tolerance in carnivorous fish. AB - Fifteen years ago, Tom Moon wrote a review on this journal in order to propose some explanations to the exacerbated glycaemic response after a glucose load or a carbohydrate meal intake observed in fish, the so-called intolerance to glucose. Before, but in most of cases after this paper, several laboratories worldwide started to make important efforts in order to better understand this strange phenotype observed in fish and that so far seemed to belong to diabetic humans only. Tom had been worked on fish metabolism for at least 30years when he proposed that mini-review and the paths opened by him in 2001 were followed by tens of fish researchers, making this paper a breaking point on the field. Fifteen years later, we propose not only to have a look to the answers given to the questions rose in that paper, but also to summarize how his career over all these years impacted the domain of glucose metabolism in fish. In the review, we will show how Tom Moon analysed at different levels (from genes up to the whole organism), using distinct experimental tools (cells, hormone or glucose injection, pumps, drugs) the questions of glucose metabolism, tolerance and nutrition in fish species. PMID- 26545983 TI - DNA methylation subgroups in melanoma are associated with proliferative and immunological processes. AB - BACKGROUND: DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity. METHODS: We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data. RESULTS: We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes. CONCLUSIONS: Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells. PMID- 26545985 TI - Wnt/beta-catenin signaling participates in the regulation of lipogenesis in the liver of juvenile turbot (Scophthalmus maximus L.). AB - In this study, the mechanism that Wnt/beta-catenin signaling inhibits lipogenesis was investigated in the liver of juvenile turbot (Scophthalmus maximus L.) by LiCl or XAV939 treatment. Wnt/beta-catenin signaling was activated by LiCl treatment or inhibited by XAV939 treatment through regulating the expression of glycogen synthase kinase-3beta (GSK-3beta) and Wnt10b. In addition, the expression of lipoprotein lipase (LPL), fatty acid synthetase (FAS), peroxisome proliferator-activated receptor gamma (PPARgamma), and CCAAT/enhancer binding protein alpha (C/EBPalpha) was inhibited by LiCl treatment, but induced by XAV939 treatment. In the plasma of juvenile turbot, the level of nonesterified fatty acid (NEFA), glycerol, triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) was decreased by LiCl treatment, which was related to the decrease of the activity of LPL and FAS. Thus the inhibitory effect of Wnt/beta-catenin signaling on lipogenesis was associated with the expression of key enzymes and transcriptional factors. Wnt/beta-catenin signaling may participate in inhibiting lipogenesis by inhibiting the expression of PPARgamma and C/EBPalpha in the liver of juvenile turbot. PMID- 26545988 TI - Etiology of Acute Bacterial Meningitis in Iran: a Systematic Review. AB - Acute bacterial meningitis (ABM) is one of the most severe infectious diseases, causing neurologic sequel, and a case fatality rate of 20-30%. The aim of this paper was to summarize the main causes of ABM in Iran. We searched the data for relevant articles using meningitis, etiology, and Iran as search terms. We found 23 papers for inclusion in the review that focused specifically on the ABM, addressing etiology and acute meningitis. Finally, during the 23 years, a total of 18163 cases were recorded, and 1074 cases of which met the criteria for bacterial meningitis. The most common agent associated with bacterial meningitis was S. pneumoniae, followed by H. influenzae, Enterobacter spp., N. meningitidis, and group B streptococcus. The total incidence of ABM during 1991 to 2002 was higher than during 2003-2013. S. pneumoniae still remains a main cause of bacterial meningitis. For improved outcomes, studies are needed to further clarify the etiology of meningitis in Iran, explore simple, accurate, and practical diagnostic tools as PCR, and investigate the most appropriate specific and supportive interventions to manage and prevent meningitis as vaccination. PMID- 26545986 TI - Baseline characteristics, analysis plan and report on feasibility for the Prevention Of Decline in Cognition After Stroke Trial (PODCAST). AB - BACKGROUND: A common complication after stroke is development of cognitive impairment and dementia. However, effective strategies for reducing the risk of developing these problems remain undefined. Potential strategies include intensive lowering of blood pressure (BP) and/or lipids. This paper summarises the baseline characteristics, statistical analysis plan and feasibility of a randomised control trial of blood pressure and lipid lowering in patients post stroke with the primary objective of reducing cognitive impairment and dementia. METHODS: The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) was a multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial internal pilot trial running in secondary and primary care. Participants without dementia were enrolled 3-7 months post ischaemic stroke or spontaneous intracerebral haemorrhage, and randomised to intensive versus guideline BP lowering (target systolic BP <125 mmHg versus <140 mmHg); patients with ischaemic stroke were also randomised to intensive or guideline lipid lowering (target LDL cholesterol <1.4 mmol/L versus <3 mmol/L). The primary outcome was the Addenbrooke's Cognitive Examination-Revised; a key secondary outcome was to assess feasibility of performing a large trial of one or both interventions. Data are number (%) or mean (standard deviation). The trial was planned to last for 8 years with follow-up between 1 and 8 years. The plan for reporting the main results is included as Additional file 2. RESULTS: 83 patients (of a planned 600) were recruited from 19 UK sites between 7 October 2010 and 31 January 2014. Delays, due to difficulties in the provision of excess treatment costs and to complexity of follow-up, led to few centres taking part and a much lower recruitment rate than planned. Patient characteristics at baseline were: age 74 (SD 7) years, male 64 (77 %), index stroke ischaemic 77 (93 %), stroke onset to randomisation 4.5 [SD 1.3] months, Addenbrooke's Cognitive Examination Revised 86 (of 100, SD 8), Montreal Cognitive Assessment 24 (of 30, SD 3), BP 147/82 (SD 19/11) mmHg, total cholesterol 4.0 (SD 0.8) mmol/L and LDL cholesterol 2.0 (SD 0.7) mmol/L, modified Rankin Scale 1.1 (SD 0.8). CONCLUSION: Limited recruitment suggests that a large trial is not feasible using the current protocol. The effects of the interventions on BP, lipids, and cognition will be reported in the main publication. TRIAL REGISTRATION: ISRCTN85562386 registered on 23 September 2009. PMID- 26545987 TI - Totally robotic repair of atrioventricular septal defect in the adult. AB - BACKGROUND: Atrioventricular septal defect (AVSD) accounts for up to 3 % of congenital cardiac defects, which is routinely repaired via median sternotomy. Minimally invasive approach such as endoscopic or robotic assisted repair for AVSD has not been reported in the literature. With the experience with robotic mitral valve surgery and congenital defect repair, we initiated robotic AVSD repair in adults. CASE PRESENTATION: In this report, we presented three cases of successful repair of partial and intermediate AVSD by using da Vinci SI surgical system (Intuitive Surgical, Inc., Sunnyvale, CA). CONCLUSIONS: Totally robotic AVSD repair via right atriotomy could be safely performed in adults and it may provide superior cosmesis with the comparable surgical outcome of the repair via sternotomy. PMID- 26545989 TI - Total Knee Arthroplasty: Does the Tibial Medial Side Defect Affect Outcome? AB - Primary knee osteoarthritis (OA) is one of the degenerative diseases that destroy auricular cartilage within knee joint and cause pain, varies deformity, decrease knee function. Total knee arthroplasty (TKA) is an effective intervention in order to relieve pain, improve function and QOL (quality of life) in patients with severe osteoarthritis of the knees that have different degrees of varus deformity. However, we are not aware of any study to shows if medial side defect in tibia has any association with outcome. We conceive this study of finding out if medial side defect of tibia affects the outcome. 124 patients (143 knees) with primary knee OA with different stages of defects participated in this study. Patients classified into two groups based on Rand classification of knee defects (patients with Rand I and II in group 1 and patients with Rand III and IV in group 2). Pain and knee alignment have been measured by Visual analog scale (VAS) and 3-joint X-ray and quality of life, knee function and radiographic have been measured by questionnaires of SF 36, WOMAC and KSS score. The mean follow-up was 18. 2 mounts (range 12 to 23 months). The results showed that all of the parameters improved significantly within groups (P<=0.001). Comparison TKA between two groups in the postoperative analysis shows that there was a significant difference between groups in pain, radiographic and functional KSS and WOMAC score (P<=0.05). So group 1 had better results in these parameters than group 2 after surgery. TKA is an effective intervention for all patients with severe osteoarthritis and varus deformity. However, the severity of medial tibial defects is an important determinant of outcome. Patients with a more severe deformity have less favorable outcome. PMID- 26545990 TI - Restorative Effect of Vitamin D Deficiency on Knee Pain and Quadriceps Muscle Strength in Knee Osteoarthritis. AB - Both vitamin D deficiency and quadriceps muscle weakness are associated with knee osteoarthritis (KOA) and pain. The aim of this study was to determine the restorative effect of vitamin D deficiency on pain and quadriceps muscle strength in knee osteoarthritis. Patients with KOA aged >=30 years, the presence of knee pain for at least one month or longer and serum 25-hydroxyvitamin (25-OHD) deficiencies were recruited in the study. Participants with KOA compatible with Kellgren-Lawrence grade 4, joint instability, and effusion, history of surgery or inflammatory arthropathies were excluded. Serum 25-OHD was assessed by ELISA method and concentrations<20 ng/ml was considered deficiency. Quadriceps muscle strength was measured by dynamometry method and intensity of knee pain by Western Ontario and McMaster University Osteoarthritis index scored by Likert scale and visual analog scale. All participants received 50.000 IU oral cholecalciferol weekly for at least two months. The influence of raising serum 25-OHD on quadriceps muscle strength and pain was assessed by calculation of mean changes from baseline at the end of the treatment period using paired t-test. A total of 67 patients with mean age of 50+/-6.6 years of age were treated for 2 months. Serum 25-OHD reached to sufficient levels in all except one patient. At the end of the study period, serum 25-OHD and quadriceps muscle strength increased significantly as compared with baseline (P=0.007 and P=0.002, respectively), whereas knee pain decreased significantly based on Western Ontario and McMaster University Osteoarthritis index (P=0.001)as well as visual analogue scale scores (P=0.001). These findings indicated that correction of vitamin D deficiency in patients with KOA exerts a significant favorable effect on quadriceps muscle strength and knee pain. PMID- 26545991 TI - Comparative Evaluation of EGF in Oral Lichen Planus and Oral Squamous Cell Carcinoma. AB - Oral lichen planus (OLP) is classified as a potential malignant disorder, and epidermal growth factor (EGF) may play a key role in cancer development. The aim of this study was to compare serum and saliva EGF among patients with OLP and oral squamous cell carcinoma (OSCC). A cross-sectional study was performed on 27 patients with OLP (10 reticular and 17 atrophic-erosive forms), 27 patients with OSCC and 27 healthy control group. The study was conducted at the Cancer Department, Clinic of Oral Medicine, Tehran University of Medical Sciences. The serum and saliva EGF were assayed by ELISA method. Statistical analysis of ANOVA was used. The mean serum EGF in OLP and OSCC patients was significantly lower compared to healthy control group (P<0.05), but no significant difference was observed between OLP and OSCC patients. There was no significant difference in mean salivary EGF among groups. As serum EGF levels appear to be statistically similar in OLP and OSCC, it seems that EGF might play a role in the pathogenesis of OLP and its cancerization. PMID- 26545992 TI - Evaluation of Cardiac Systolic Function in Cirrhotic Patients Undergoing Liver Transplantation. AB - We assessed different systolic cardiac indices to detect left and right ventricular systolic dysfunction in cirrhotic patients before liver transplantation. Between 2010-2011, 81 consecutive individuals with confirmed hepatic cirrhosis who were a candidate for liver transplantation were enrolled in this study. A total of 32 age and sex matched healthy volunteers were also selected as the control group. A detailed two-dimensional, Color Flow Doppler, and Tissue Doppler echocardiography were performed in all patients and control participants. Left atrial diameter and area, right atrial area, left ventricular end diastolic volume, and basal right ventricular diameter were significantly higher in the cirrhotic group (P<0.05). Left ventricular ejection fraction, stroke volume, left ventricular outflow tract velocity time integral and tricuspid annular plane systolic excursion were also higher in the cirrhotic group (P<0.05). Peak systolic velocities of tricuspid annulus, basal segment of RV free wall and basal segment of septal wall, peak strains of basal and mid portions of septal wall, mid portion of lateral wall and peak strain rates of basal and mid portions of septal and lateral walls were higher significantly in cirrhotic group, as well (P<0.05). Isovolumic contraction time, LV systolic time interval and Tei indexes of left and right ventricles which all are representatives of systolic dysfunction were higher in cirrhosis. Peak systolic velocity of a mid-segment of the lateral wall was lower in the cirrhotic group (P<0.05) as well. Most of the cirrhotic patients display signs of cardiovascular disturbances that become more manifest following exposure to stresses such as transplantation. Cardiac failure is an important cause of death following liver transplantation. Because of the load dependency we cannot use most of the cardiac systolic indices for evaluation of systolic function in cirrhotic patients. Thus, we suggest that LV systolic time interval and Tei indices of left and right ventricles might be useful indices in the evaluation of systolic function in cirrhotic patients. PMID- 26545993 TI - Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System. AB - Exposure to stress leads to physiological changes called "stress response" which are the result of the changes in the adrenomedullary hormone system, hypothalamus pituitary-adrenal (HPA) and sympathetic nervous system (SNS) activity. In the present study, the effects of chronic physical and psychological stress and also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R) injuries have been studied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 min reperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was done chemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes in heart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP) and rate product pressure (RPP) in both physical and psychological stress groups decreased significantly compared to those in control group (P<0.05), but there was no significant difference between physical and psychological stress groups. Infarct size significantly increased in both physical and psychological stress groups and control group(P<0.05. Sympathectomy before induction of stress led to the elimination of the deleterious effects of stress as compared with stress groups (P<0.05). These results show that induction of chronic physical and psychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seems that increased sympathetic activity in response to stress is responsible for these adverse effects of stress on ischemic/reperfused heart. PMID- 26545994 TI - Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins. AB - Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs). PMID- 26545995 TI - Knowledge, Attitude and Practice of General Practitioners toward Complementary and Alternative Medicine: a Cross-Sectional Study. AB - Orientation of public and physicians to the complementary and alternative medicine (CAM) is one of the most prominent symbols of structural changes in the health service system. The aim of his study was a determination of knowledge, attitude, and practice of general practitioners in complementary and alternative medicine. This cross- sectional study was conducted in Qazvin, Iran in 2013. A self-administered questionnaire was used for collecting data including four information parts: population information, physicians' attitude and knowledge, methods of getting information and their function. A total of 228 physicians in Qazvin comprised the population of study according to the deputy of treatment's report of Qazvin University of Medical Sciences. A total of 150 physicians were selected randomly, and SPSS Statistical program was used to enter questionnaires' data. Results were analyzed as descriptive statistics and statistical analysis. Sixty percent of all responders were male. About sixty (59.4) percent of participating practitioners had worked less than 10 years.96.4 percent had a positive attitude towards complementary and alternative medicine. Knowledge of practitioners about traditional medicine in 11 percent was good, 36.3% and 52.7% had average and little information, respectively. 17.9% of practitioners offered their patients complementary and alternative medicine for treatment. Although there was little knowledge among practitioners about traditional medicine and complementary approaches, a significant percentage of them had attitude higher than the lower limit. PMID- 26545996 TI - The Effect of Foot Reflexology on Anxiety, Pain, and Outcomes of the Labor in Primigravida Women. AB - Reflexology is a technique used widely as one of non-pharmacological pain management techniques. The present study aimed to review and determine the effect of foot reflexology on anxiety, pain and outcomes of the labor in primigravida women. This clinical trial study was conducted on 80 primigravida mothers who were divided randomly into an intervention group (Foot reflexology applied for 40 min, n=40) and control group (n=40). The pain intensity was scored immediately after the end of intervention and at 30,60 and 120 min after the intervention in both groups, based on McGill Questionnaire for Pain Rating Index (PRI). Spielberger State-Trait Anxiety Inventory (STAI) was completed before and after intervention in both groups. Duration of labor phases, the type of labor and Apgar scores of the infant at the first and fifth minute were recorded in both groups. Descriptive and inferential statistics methods (t-test and chi-square test) were applied in analyzing data. Application of reflexology technique decreased pain intensity (at 30, 60 and 120 min after intervention) and duration of labor as well as anxiety level significantly (P<0.001). Furthermore, a significant difference was observed between two groups in terms of the frequency distribution of the type of labor and Apgar score (P<0.001). Results of this study show that reflexology reduces labor pain intensity, duration of labor, anxiety, frequency distribution of natural delivery and increases Apgar scores. Using this non-invasive technique, obstetricians can achieve, to some extent, to one of the most important goals of midwifery as pain relief and reducing anxiety during labor and encourage the mothers to have a vaginal delivery. PMID- 26545997 TI - Benign Duodenocolic Fistula: a Case Report. AB - Benign duodenocolic fistula (DCF), known as a fistula between the duodenum and colon with or without cecum of nonmalignant origin, is an unusual complication of different gastrointestinal diseases. The present paper records a case in which the patient presented with chronic diarrhea, abdominal pain, weight loss as well as having a history of gastric ulcer. Most frequently the condition presents with signs of malabsorption such as weight loss and diarrhea, but other symptoms include nausea, vomiting (sometimes with fecal), and abdominal pain. Gastrointestinal inflammatory conditions are the usual causes. The most common ones are perforated duodenal ulcer and Crohn's disease. Barium enemas are usually diagnostic. Treatment consists of excising the fistula and repairing the duodenal and colonic defects. Closure of the fistula provides quick relief. PMID- 26545998 TI - Urinary Tract Infection with Candida glabrata in a Patient with Spinal Cord Injury. AB - Candida glabrata was thought to be a primarily non-pathogenic organism. However, with the ever-increasing population of immunocompromised individuals, it is considered to be an opportunistic pathogen. Patients with spinal cord injuries often using a long-term urinary catheter and are high risk for Urinary Tract Infections. This case report describes a patient with spinal cord injury (thoracic region) with a pure culture of Candida glabrata in a urine sample. PMID- 26545999 TI - Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: Report of a Rare Case in Newborn. AB - Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare and the most severe form of functional intestinal obstruction in the newborn. The characteristic features of this congenital and fatal disease are abdominal distension, absent or decreased bowel peristalsis. Abdominal distension is a consequence of the distended, unobstructed urinary bladder with or without hydronephrosis. We present a case of female newborn with antenatal ultrasound revealing a large cystic mass in pelvic with urinary tract origin, abdominal distension, a peristalsis of the intestine and micro colon. PMID- 26546001 TI - Data-Driven Reversible Jump for QTL Mapping. AB - We propose a birth-death-merge data-driven reversible jump (DDRJ) for multiple QTL mapping where the phenotypic trait is modeled as a linear function of the additive and dominance effects of the unknown QTL genotypes. We compare the performance of the proposed methodology, usual reversible jump (RJ) and multiple interval mapping (MIM), using simulated and real data sets. Compared with RJ, DDRJ shows a better performance to estimate the number of QTLs and their locations on the genome mainly when the QTLs effect is moderate, basically as a result of better mixing for transdimensional moves. The inclusion of a merge step of consecutive QTLs in DDRJ is efficient, under tested conditions, to avoid the split of true QTL's effects between false QTLs and, consequently, selection of the wrong model. DDRJ is also more precise to estimate the QTLs location than MIM in which the number of QTLs need to be specified in advance. As DDRJ is more efficient to identify and characterize QTLs with smaller effect, this method also appears to be useful and brings contributions to identifying single-nucleotide polymorphisms (SNPs) that usually have a small effect on phenotype. PMID- 26546000 TI - Development of a rapid and simplified protocol for direct bacterial identification from positive blood cultures by using matrix assisted laser desorption ionization time-of- flight mass spectrometry. AB - BACKGROUND: Bloodstream infections represent serious conditions carrying a high mortality and morbidity rate. Rapid identification of microorganisms and prompt institution of adequate antimicrobial therapy is of utmost importance for a successful outcome. Aiming at the development of a rapid, simplified and efficient protocol, we developed and compared two in-house preparatory methods for the direct identification of bacteria from positive blood culture flasks (BD BACTEC FX system) by using matrix-assisted laser desorption ionization time-of flight mass spectrometry (MALDI TOF MS). Both methods employed saponin and distilled water for erythrocyte lysis. In method A the cellular pellet was overlaid with formic acid on the MALDI TOF target plate for protein extraction, whereas in method B the pellet was exposed to formic acid followed by acetonitrile prior to placing on the target plate. RESULTS: Best results were obtained by method A. Direct identification was achieved for 81.9 % and 65.8 % (50.3 % and 26.2 % with scores >2.0) of organisms by method A and method B, respectively. Overall concordance with final identification was 100 % to genus and 97.9 % to species level. By applying a lower cut-off score value, the levels of identification obtained by method A and method B increased to 89.3 % and 77.8 % of organisms (81.9 % and 65.8 % identified with scores >1.7), respectively. Using the lowered score criteria, concordance with final results was obtained for 99.3 % of genus and 96.6 % of species identifications. CONCLUSION: The reliability of results, rapid performance (approximately 25 min) and applicability of in-house method A have contributed to implementation of this robust and cost-effective method in our laboratory. PMID- 26546002 TI - Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1. AB - The Saccharomyces cerevisiae type 2C protein phosphatase Ptc1 is required for a wide variety of cellular functions, although only a few cellular targets have been identified. A genetic screen in search of mutations in protein kinase encoding genes able to suppress multiple phenotypic traits caused by the ptc1 deletion yielded a single gene, MKK1, coding for a MAPK kinase (MAPKK) known to activate the cell-wall integrity (CWI) Slt2 MAPK. In contrast, mutation of the MKK1 paralog, MKK2, had a less significant effect. Deletion of MKK1 abolished the increased phosphorylation of Slt2 induced by the absence of Ptc1 both under basal and CWI pathway stimulatory conditions. We demonstrate that Ptc1 acts at the level of the MAPKKs of the CWI pathway, but only the Mkk1 kinase activity is essential for ptc1 mutants to display high Slt2 activation. We also show that Ptc1 is able to dephosphorylate Mkk1 in vitro. Our results reveal the preeminent role of Mkk1 in signaling through the CWI pathway and strongly suggest that hyperactivation of Slt2 caused by upregulation of Mkk1 is at the basis of most of the phenotypic defects associated with lack of Ptc1 function. PMID- 26546005 TI - The 38th annual meeting of the Association of Colon and Rectal Surgeons of India in New Delhi, India. PMID- 26546003 TI - Expression Differentiation Is Constrained to Low-Expression Proteins over Ecological Timescales. AB - Protein expression level is one of the strongest predictors of protein sequence evolutionary rate, with high-expression protein sequences evolving at slower rates than low-expression protein sequences largely because of constraints on protein folding and function. Expression evolutionary rates also have been shown to be negatively correlated with expression level across human and mouse orthologs over relatively long divergence times (i.e., ~100 million years). Long term evolutionary patterns, however, often cannot be extrapolated to microevolutionary processes (and vice versa), and whether this relationship holds for traits evolving under directional selection within a single species over ecological timescales (i.e., <5000 years) is unknown and not necessarily expected. Expression is a metabolically costly process, and the expression level of a particular protein is predicted to be a tradeoff between the benefit of its function and the costs of its expression. Selection should drive the expression level of all proteins close to values that maximize fitness, particularly for high-expression proteins because of the increased energetic cost of production. Therefore, stabilizing selection may reduce the amount of standing expression variation for high-expression proteins, and in combination with physiological constraints that may place an upper bound on the range of beneficial expression variation, these constraints could severely limit the availability of beneficial expression variants. To determine whether rapid-expression evolution was restricted to low-expression proteins owing to these constraints on highly expressed proteins over ecological timescales, we compared venom protein expression levels across mainland and island populations for three species of pit vipers. We detected significant differentiation in protein expression levels in two of the three species and found that rapid-expression differentiation was restricted to low-expression proteins. Our results suggest that various constraints on high-expression proteins reduce the availability of beneficial expression variants relative to low-expression proteins, enabling low-expression proteins to evolve and potentially lead to more rapid adaptation. PMID- 26546004 TI - Local administration of gentamicin collagen sponge in surgical excision of sacrococcygeal pilonidal sinus disease: a systematic review and meta-analysis of the literature. AB - Surgical site infections occur in up to 24 % of patients after surgical excision of sacrococcygeal pilonidal sinus disease with primary wound closure. Local administration of antibiotics by a gentamicin collagen sponge could reduce this infection rate. The objective of this systematic review and meta-analysis was to evaluate the effect of a gentamicin collagen sponge on outcome after surgical excision in patients with sacrococcygeal pilonidal sinus disease. A structured literature search was performed in the PubMed, Embase, The Cochrane Library, and Scopus databases. Studies comparing surgical excision of sacrococcygeal pilonidal sinus disease with versus without a gentamicin collagen sponge were included. Outcome measures were surgical site infection, wound healing, and recurrence. The search strategy yielded six studies with a total of 669 patients. Three randomized controlled trials, comparing excision of pilonidal sinus disease and primary wound closure with versus without gentamicin collagen sponge, were eligible for inclusion in the meta-analysis (319 patients), demonstrating a trend towards reduced surgical site infections after administration of gentamicin collagen sponge [absolute risk reduction 20 %, 95 %-confidence interval (CI) 1-41 %, p = 0.06]. The wound healing (absolute risk reduction 22 %, 95 % CI 32-77 %, p = 0.42) and recurrence rate (absolute risk reduction 8 %, 95 % CI 7-22 %, p = 0.30) were not significantly different between both groups. Administration of a gentamicin collagen sponge after surgical excision of sacrococcygeal pilonidal sinus disease showed no significant influence on wound healing and recurrence rate, but a trend towards a reduced incidence of surgical site infections. Therefore, additional larger well-designed randomized controlled trials are required. PMID- 26546006 TI - A mechanism for constructing a durable purse-string during transanal total mesorectal excision. PMID- 26546007 TI - The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contain multiple S-palmitoylation sites. AB - Expression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN1 4) on distal dendrites of neurons is suggested to modify synaptic integration in the central nervous system. However, the mechanisms of dendritic localization are not fully understood. Recent studies have revealed that S-palmitoylation plays an important role in the enrichment of various molecules at the postsynaptic membrane. Thus, we performed an acyl-biotinyl exchange assay, and found that HCN1, HCN2, and HCN4, but not HCN3, were S-palmitoylated in HEK293 cells. Mutation of multiple intracellular cysteine residues at the N-terminus of HCN2 was required for complete inhibition of S-palmitoylation. However, this mutagenesis had a minimal effect on surface expression of HCN2 proteins or electrophysiological properties of HCN2 current when expressed in HEK293 cells or in Xenopus oocytes. These findings provide insight into the physiological roles of S-palmitoylation of HCN channels in native neurons. PMID- 26546008 TI - Partial cavopulmonary assist from the inferior vena cava to the pulmonary artery improves hemodynamics in failing Fontan circulation: a theoretical analysis. AB - Cavopulmonary assist (CPA) for failing Fontan patients remains a challenging issue in the clinical setting. To evaluate the effectiveness of a partial CPA from the inferior vena cava (IVC) to the pulmonary artery (PA), we performed a theoretical analysis using a computational model of the Fontan circulation. Cardiac chambers and vascular systems were described as the time-varying elastance model and the modified three-element Windkessel model, respectively. A rotational pump described as a non-linear function was inserted between the IVC and the PA. When pulmonary vascular resistance index varied from 2.1 to 5.9 Wood units m(2), the partial CPA maintained cardiac index as efficiently as total CPA and markedly reduced the IVC pressure compared with total CPA. However, the partial CPA increased the superior vena cava pressure substantially. The modification from total to partial CPA is potentially an effective alternative in failing Fontan patients suffering from high IVC pressure. PMID- 26546009 TI - Modulation of unloading-induced bone loss in mice with altered ERK signaling. AB - Genetic variations mediate skeletal responsiveness to mechanical unloading, with individual space travelers exhibiting large variations in the extent of bone loss. We previously identified genomic regions harboring several hundred genes that can modulate the magnitude of skeletal adaptation to mechanical unloading. Here, bioinformatic filters aided in shortlisting 30 genes with bone-related and mechanoregulatory roles. The genes CD44, FGF2, NOD2, and Fas, all associated with ERK signaling, were then functionally tested in hindlimb-unloaded (HLU) knockout (KO) mice. Compared to their respective normally ambulating wildtype (WT) controls, all KO strains, except Fas mice, had lower trabecular bone volume, bone volume fraction, and/or trabecular number. For cortical bone and compared to ambulatory WT mice, CD44(-/-) had impaired properties while FGF2(-/-) showed enhanced indices. NOD2(-/-) and Fas(-/-) did not have a cortical phenotype. In all KO and WT groups, HLU resulted in impaired trabecular and cortical indices, primarily due to trabecular tissue loss and mitigation of cortical bone growth. The difference in trabecular separation between HLU and ambulatory controls was significantly greater in CD44(-/-) and NOD2(-/-) mice than in WT mice. In cortical bone, differences in cortical thickness, total pore volume, and cortical porosity between HLU and controls were aggravated in CD44(-/-) mice. In contrast, deletion of NOD2 and Fas genes mitigated the differences in Po.V between HLU and control mice. Together, we narrowed a previous list of QTL-derived candidate genes from over 300 to 30, and showed that CD44, NOD2, and Fas have distinct functions in regulating changes in trabecular and cortical bone indices during unloading. PMID- 26546010 TI - A randomized, double-blind, crossover comparison of novel continuous bed motion versus traditional bed position whole-body PET/CT imaging. AB - PURPOSE: Continuous bed motion has recently been introduced for whole-body PET/CT, and represents a paradigm shift towards individualized and flexible acquisition without the limitations of bed position-based planning. Increased patient comfort due to lack of abrupt table position changes may be another albeit still unproven advantage. For robust clinical implementation, image quality and quantitative accuracy should at least be equal to the prior standard of bed position-based step-and-shoot imaging. METHODS: The study included 68 consecutive patients referred for whole-body PET/CT for various malignancies. The patients underwent traditional step-and-shoot and novel continuous bed motion acquisition in the same session in a randomized crossover design. The patients and two independent observers were blinded to the sequence of scan techniques. Patient comfort/satisfaction was examined using a standardized questionnaire. SUVs were compared for reference tissue (liver, muscle) and tumour lesions. PET image quality and misalignment with CT images were evaluated on a scale of 1 - 4. RESULTS: Patients preferred continuous bed motion over step-and-shoot (P = 0.0001). It was considered to be more relaxing (38 % vs. 8 %), quieter (34 % vs. 8 %), and more fluid (64 % vs. 8 %). Image quality, SUV and CT misalignment did not differ between the techniques. Continuous bed motion resulted in better end plane image quality (P < 0.0001). Regardless of the technique, second examinations had significantly higher tumour lesion SUVmax values (P = 0.0002), and a higher CT misalignment score (P = 0.0017). CONCLUSION: Oncological PET/CT with continuous bed motion enhances patient comfort and is associated with image quality at least comparable to that with traditional bed position-based step-and shoot acquisition.qq. PMID- 26546016 TI - Do Socioeconomic Inequalities in Neonatal Mortality Reflect Inequalities in Coverage of Maternal Health Services? Evidence from 48 Low- and Middle-Income Countries. AB - OBJECTIVES: To examine socioeconomic and health system determinants of wealth related inequalities in neonatal mortality rates (NMR) across 48 low- and middle income countries. METHODS: We used data from Demographic and Health Surveys conducted between 2006 and 2012. Absolute and relative inequalities for NMR and coverage of antenatal care, facility-based delivery, and Caesarean delivery were measured using the Slope Index of Inequality and Relative Index of Inequality, respectively. Meta-regression was used to assess whether variation in the magnitude of NMR inequalities was associated with inequalities in coverage of maternal health services, and whether country-level economic and health system factors were associated with mean NMR and socioeconomic inequality in NMR. RESULTS: Of the three maternal health service indicators examined, the magnitude of socioeconomic inequality in NMR was most strongly related to inequalities in antenatal care. NMR inequality was greatest in countries with higher out-of pocket health expenditures, more doctors per capita, and a higher adolescent fertility rate. Determinants of lower mean NMR (e.g., higher government health expenditures and a greater number of nurses/midwives per capita) differed from factors associated with lower NMR inequality. CONCLUSIONS: Reducing the financial burden of maternal health services and achieving universal coverage of antenatal care may contribute to a reduction in socioeconomic differences in NMR. Further investigation of the mechanisms contributing to these cross-national associations seems warranted. PMID- 26546011 TI - Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans. AB - Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments. PMID- 26546017 TI - Prevalence and Correlates of Hazardous Drinking among Female Sex Workers in 13 Mexican Cities. AB - AIMS: To describe the prevalence and correlates of hazardous drinking among female sex workers (FSWs) at 13 sites throughout Mexico. METHODS: FSWs (N = 1089) who were enrolled in a brief sexual risk reduction intervention (Mujer Segura) were queried about their sexual risk and substance use practices and their work contexts. Participants were classified as hazardous or non-hazardous drinkers based on the Alcohol Use Disorders test (AUDIT-C). Logistic regression models were used to examine individual, contextual, and community-level factors as correlates of hazardous drinking. RESULTS: Ninety-two percent of participants reported alcohol consumption in the past month. Among drinkers (N = 1001), 83% met AUDIT-C criteria for hazardous drinking. Factors that were independently associated with hazardous drinking included: drug use in the past month (adjusted odds ratio (AOR) = 3.31; 95% CI 1.29-8.45), being a cigarette smoker (AOR = 1.71; 95% CI 1.13-2.58), being a barmaid or dance hostess (AOR = 3.40; 95% CI 1.95 5.91), alcohol use before or during sex with clients (AOR = 7.78; 95% CI 4.84 12.52), and working in a city with a higher marginalization index (AOR = 1.07; 95% CI 1.04-1.11). CONCLUSIONS: Findings support the high prioritization by public health authorities of alcohol prevention and treatment programs for FSWs. PMID- 26546018 TI - Distracted by danger: Temporal and spatial dynamics of visual selection in the presence of threat. AB - Threatening stimuli are known to influence attentional and visual processes in order to prioritize selection. For example, previous research showed faster detection of threatening relative to nonthreatening stimuli. This has led to the proposal that threatening stimuli are prioritized automatically via a rapid subcortical route. However, in most studies, the threatening stimulus is always to some extent task relevant. Therefore, it is still unclear if threatening stimuli are automatically prioritized by the visual system. We used the additional singleton paradigm with task-irrelevant fear-conditioned distractors (CS+ and CS-) and indexed the time course of eye movement behavior. The results demonstrate automatic prioritization of threat. First, mean latency of saccades directed to the neutral target was increased in the presence of a threatening (CS+) relative to a nonthreatening distractor (CS-), indicating exogenous attentional capture and delayed disengagement of covert attention. Second, more error saccades were directed to the threatening than to the nonthreatening distractor, indicating a modulation of automatically driven saccades. Nevertheless, cumulative distributions of the saccade latencies showed no modulation of threat for the fastest goal-driven saccades, and threat did not affect the latency of the error saccades to the distractors. Together these results suggest that threatening stimuli are automatically prioritized in attentional and visual selection but not via faster processing. Rather, we suggest that prioritization results from an enhanced representation of the threatening stimulus in the oculomotor system, which drives attentional and visual selection. The current findings are interpreted in terms of a neurobiological model of saccade programming. PMID- 26546019 TI - Genome-wide analysis and expression patterns of ZF-HD transcription factors under different developmental tissues and abiotic stresses in Chinese cabbage. AB - The ZF-HD gene family plays an important role in plant developmental processes and stress responses. However, the function of the ZF-HD genes in Chinese cabbage remains largely unknown. Chinese cabbage (Brassica rapa ssp. pekinensis) is a member of one of the most important leaf vegetables grown worldwide. The entire Chinese cabbage genome sequence has been determined, and more than forty thousand proteins have been identified to date. In this study, 31 ZF-HD genes were identified in Chinese cabbage. We show here that the BraZF-HD genes could be categorized into ZHD and MIF subfamilies. Among them, ZHD genes are plant specific, nearly all intronless, and related to MINI ZINC FINGER genes that possess only the zinc finger. Phylogenetic analysis suggested that ZHDs have expanded considerably during angiosperm evolution. In addition, the ZHD group has 24 members, which is twice as much as the Arabidopsis ZHD group, indicating that the Chinese cabbage ZHD genes have been retained more frequently than other group genes. Real-time PCR analysis showed that most of BraZF-HD genes are preferentially expressed in flower. Furthermore, most of these genes are significantly induced under photoperiod or vernalization conditions, as well as abiotic stresses. Thereby implying that they may play important roles in these processes. This study provides insight into the evolution of ZF-HD genes in Chinese cabbage genome and may aid efforts to further characterize the function of these predicted ZF-HD genes in flowering and resistance. PMID- 26546020 TI - Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception. AB - The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) provide recommendations for use of emergency contraceptive pills (ECPs), including levonorgestrel (LNG) and combined oral contraceptives (COCs). A new ECP formulation, ulipristal acetate (UPA), is now available worldwide. To determine whether LNG, UPA or COC (Yuzpe) ECPs are safe for women with certain characteristics or medical conditions, we searched the PubMed and Cochrane databases for articles published from date of inception until May 2015 pertaining to the safety of LNG, UPA or Yuzpe ECP use. For direct evidence, we considered studies that looked at safety outcomes among women with certain medical conditions or characteristics taking ECPs compared with women not taking ECPs. For indirect evidence, we considered studies that reported pharmacokinetic (PK) data for ECP use among women with certain medical conditions or characteristics and studies that reported safety outcomes among healthy women taking ECPs. Five studies provided direct evidence; of these five studies, four examined LNG or Yuzpe use among pregnant or breastfeeding women, and one reported risk of ectopic pregnancy among women repeatedly using LNG ECPs. Poor pregnancy outcomes were rare among pregnant women who used LNG or Yuzpe ECPs during the conception cycle or early pregnancy. Breastfeeding outcomes did not differ between women exposed to LNG ECP and those unexposed, and there was no increased risk of ectopic pregnancy versus intrauterine pregnancy after repeated use of LNG ECPs compared with nonuse. Forty-five studies provided indirect evidence. One PK study demonstrated that LNG passes into breastmilk but in minimal quantities. In addition, nine studies examined pregnancy outcomes following ECP failure among healthy women, and 35 articles reported adverse events. Studies suggest that serious adverse events are rare among women taking any of these ECP formulations. IMPLICATIONS: Evidence on safety of ECPs among women with characteristics or medical conditions listed within WHO and CDC family planning guidance is limited. However, both direct and indirect evidence for our study question did not suggest any special safety concerns for the use of ECPs among women with particular medical conditions or personal characteristics, such as pregnancy, lactation or frequent ECP use. PMID- 26546021 TI - Hormonal contraception among electronic cigarette users and cardiovascular risk: a systematic review. AB - BACKGROUND: Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. STUDY DESIGN: Systematic review. METHODS: We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol or glycerol. RESULTS: No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e cigarette use. These markers generally remained normal, even when significant changes were observed. In three studies, changes were less pronounced after e cigarette use than cigarette use. One MI was reported among 1012 people exposed to e-cigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. CONCLUSION: We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarette users in the general population and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes. PMID- 26546022 TI - Information filtering in resonant neurons. AB - Neuronal information transmission is frequency specific. In single cells, a band pass like frequency preference can arise from the subthreshold dynamics of the membrane potential, shaped by properties of the cell's membrane and its ionic channels. In these cases, a cell is termed resonant and its membrane impedance spectrum exhibits a peak at non-vanishing frequencies. Here, we show that this frequency selectivity of neuronal response amplitudes need not translate into a similar frequency selectivity of information transfer. In particular, neurons with resonant but linear subthreshold voltage dynamics (without threshold) do not show a resonance of information transfer at the level of subthreshold voltage; the corresponding coherence has low-pass characteristics. Interestingly, we find that when combined with nonlinearities, subthreshold resonances do shape the frequency dependence of coherence and the peak in the subthreshold impedance translates to a peak in the coherence function. In other words, the nonlinearity inherent to spike generation allows a subthreshold impedance resonance to shape a resonance of voltage-based information transfer. We demonstrate such nonlinearity mediated band-pass filtering of information at frequencies close to the subthreshold impedance resonance in three different model systems: the resonate and-fire model, the conductance-based Morris-Lecar model, and linear resonant dynamics combined with a simple static nonlinearity. In the spiking neuron models, the band-pass filtering is most pronounced for low firing rates and a high variability of interspike intervals, similar to the spiking statistics observed in vivo. We show that band-pass filtering is achieved by reducing information transfer over low-frequency components and, consequently, comes along with an overall reduction of information rate. Our work highlights the crucial role of nonlinearities for the frequency dependence of neuronal information transmission. PMID- 26546023 TI - Non-infective endocarditis with systemic embolization and recurrent stroke in systemic sclerosis. PMID- 26546025 TI - Erratum. PMID- 26546026 TI - Analysis of the Quality of Clinical Trials Published in Spanish-Language Dermatology Journals Between 1997 and 2012. AB - INTRODUCTION: The value of randomized clinical trials (RCTs) undertaken to identify an association between an intervention and an outcome is determined by their quality and scientific rigor. OBJECTIVE: To assess the methodological quality of RCTs published in Spanish-language dermatology journals. METHODS: By way of a systematic manual search, we identified all the RCTs in journals published in Spain and Latin America between 1997 (the year in which the CONSORT statement was published) and 2012. Risk of bias was evaluated for each RCT by assessing the following domains: randomization sequence generation, allocation concealment, blinding of patients and those assessing outcomes, missing data, and patient follow-up. Source of funding and conflict of interest statements, if any, were recorded for each study. RESULTS: The search identified 70 RCTs published in 21 journals. Most of the RCTs had a high risk of bias, primarily because of gaps in the reporting of important methodological aspects. The source of funding was reported in only 15 studies. DISCUSSION AND CONCLUSIONS: In spite of the considerable number of Spanish and Latin American journals, few RCTs have been published in the 15 years analyzed. Most of the RCTs published had serious defects in that the authors omitted methodological information essential to any evaluation of the quality of the trial and failed to report sources of funding or possible conflicts of interest for the authors involved. Authors of experimental clinical research in dermatology published in Spain and Latin America need to substantially improve both the design of their trials and the reporting of results. PMID- 26546027 TI - Pembrolizumab: a new Drug That Can Induce Exacerbations of Psoriasis. PMID- 26546028 TI - Inflammatory Disseminated Pruritic Porokeratosis With a Good Response to Ciclosporin. PMID- 26546024 TI - CA125-related tumor cell kinetics variables after chemotherapy in advanced ovarian cancer: a systematic review. AB - Various kinetic parameters, based on a minimum of two time points, have been built with CA125 determinations. The aim of this study is to review studies about the clinical application of CA125-related tumor cell kinetics variables in patients with advanced ovarian cancer (AOC) receiving chemotherapy. A literature search for studies about CA125-related variables in patients with AOC was undertaken on three databases, by predefined search criteria, and a selection of studies was performed. Sixty-two studies were selected. CA125-related variables were summarized in three groups: response-related, time-to-event, and other CA125 related tumor cell kinetics variables. Even though CA125 changes and half-life after chemotherapy were the most studied, other variables and two models have been well defined, and often showed an interesting power to predict survival. These kinetics variables are related to the CA125 regression curve, pre- and post chemotherapy kinetics, or are variables inferred from a population model of CA125 kinetics. PMID- 26546029 TI - Cytokine Pathways and the Role of Dysbiosis in Psoriasis, Psoriatic Arthritis, and Crohn Disease. PMID- 26546030 TI - Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis. AB - Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. PMID- 26546031 TI - Melanoma With Meyerson's Phenomenon: Clinical and Dermoscopic Features. PMID- 26546032 TI - Zinc intake and risk of Crohn's disease and ulcerative colitis: a prospective cohort study. AB - BACKGROUND: Diet plays a role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Dietary zinc may influence risk of disease through effects on autophagy, innate and adaptive immune response and maintenance of the intestinal barrier. METHODS: We analysed data from 170 776 women from the Nurses Health Study I and Nurses Health Study II, who were followed for 26 years. Zinc intake was assessed using semi-quantitative food frequency questionnaires administered every 4 years. Incident CD and UC were ascertained by medical record review. Cox proportional hazards models adjusting for potential confounders determined the independent association between zinc intake and incident disease. RESULTS: Over 3 317 550 person-years (p-y) of follow-up, we identified 269 incident cases of CD and 338 incident cases of UC. Zinc intake ranged from 9 mg/day in the lowest quintile to 27 mg/day in the highest quintile. Compared with women with the lowest quintile of intake, the multivariate hazard ratios (HR) for CD were 0.92 [95% confidence interval (CI), 0.65 - 1.29) for women in the second quintile of intake, 0.60 (95% CI, 0.40 - 0.89) for the third quintile, 0.57 (95% CI, 0.38 - 0.86) for fourth quintile and 0.74 (95% CI, 0.50 - 1.10) for the highest quintile (Ptrend = 0.003). The association was stronger for dietary zinc (HR 0.63, 95% CI, 0.43 - 0.93, comparing extreme quintiles) than for zinc intake from supplements. Neither dietary nor supplemental zinc modified risk of UC. CONCLUSIONS: In two large prospective cohorts of women, intake of zinc was inversely associated with risk of CD but not UC. PMID- 26546033 TI - Development and validation of the Japanese version of Primary Care Assessment Tool. AB - BACKGROUND: Tools for assessing quality of primary care from patient experience have never previously existed in Japan. OBJECTIVE: The aim of this study was to develop the Japanese version of Primary Care Assessment Tool (JPCAT) and to examine the validity of this tool in the assessment of the quality of primary care from patient experience in Japan. METHODS: We used a cross-sectional mail survey to test the validity and reliability of JPCAT. The questionnaire was sent to 1100 residents, 40-75 years of age, who were randomly selected from a basic resident register in Kita City, Tokyo, Japan. We examined internal consistency included Cronbach's alpha, exploratory factor analysis, multi-trait analysis and correlation between overall user satisfaction scores and JPCAT total scores. RESULTS: The tool was developed using responses from 204 residents, out of a total of 402 participants in the survey (50.7%), who had the usual sources of care. A 29-item JPCAT was constructed to include six multi-item subscales, representing each of the five primary care principles (first contact, longitudinality, comprehensiveness, coordination and community orientation). All of the multi-item scales achieved good internal consistency, item-total correlations and construct validity. The overall Cronbach's alpha coefficient was 0.90. The Spearman correlation coefficient between the JPCAT total score and the overall user satisfaction was 0.58. Scaling assumptions tests were well satisfied. The full range of possible scores was observed for all scales except the longitudinality domain. CONCLUSIONS: We developed JPCAT and examined its validity and reliability in assessing the core principles of primary care in Japan. This tool could be used for health service research in primary care. PMID- 26546034 TI - Multicenter study of quantitative computed tomography analysis using a computer aided three-dimensional system in patients with idiopathic pulmonary fibrosis. AB - PURPOSE: To evaluate the feasibility of automated quantitative analysis with a three-dimensional (3D) computer-aided system (i.e., Gaussian histogram normalized correlation, GHNC) of computed tomography (CT) images from different scanners. MATERIALS AND METHODS: Each institution's review board approved the research protocol. Informed patient consent was not required. The participants in this multicenter prospective study were 80 patients (65 men, 15 women) with idiopathic pulmonary fibrosis. Their mean age was 70.6 years. Computed tomography (CT) images were obtained by four different scanners set at different exposures. We measured the extent of fibrosis using GHNC, and used Pearson's correlation analysis, Bland-Altman plots, and kappa analysis to directly compare the GHNC results with manual scoring by radiologists. Multiple linear regression analysis was performed to determine the association between the CT data and forced vital capacity (FVC). RESULTS: For each scanner, the extent of fibrosis as determined by GHNC was significantly correlated with the radiologists' score. In multivariate analysis, the extent of fibrosis as determined by GHNC was significantly correlated with FVC (p < 0.001). There was no significant difference between the results obtained using different CT scanners. CONCLUSION: Gaussian histogram normalized correlation was feasible, irrespective of the type of CT scanner used. PMID- 26546035 TI - Erratum to: Strategies for treatment of dystonia. PMID- 26546036 TI - Erratum to: Is cognitive stability in Parkinson's disease a predictable phenomenon? A 5-year follow-up study. PMID- 26546037 TI - Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats. AB - Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson's disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially influence the function and/or survival of the implants and may be involved in an alternative mechanism of action. However, it is unclear if hRPE cells secreted trophic factors when handled in the manner used in the clinical Phase II trial. To address these questions, we investigated two neonatal hRPE cell lots, cultured in a similar manner to hRPE cells used in a Phase II clinical study, and longitudinally determined brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and pigment epithelium-derived factor concentrations in vitro and following striatal implantation into 6-hydroxydopamine-lesioned rats. The results demonstrate short-lived BDNF and FGF2 concentrations in vitro from hRPE cells grown alone or attached to gelatin microcarriers (GM)s as well as limited trophic factor concentration differences in vivo following striatal implantation of hRPE GM in 6-hydroxydopamine lesioned rats compared to sham (GM-only). The data suggest that trophic factors from neonatal hRPE cell implants likely did not participate in an alternative mechanism of action, which adds supports to a hypothesis that additional factors may have been necessary for the survival and/or function of hRPE implants and potentially the success of the Phase II clinical trial. PMID- 26546038 TI - High-density P300 enhancers control cell state transitions. AB - BACKGROUND: Transcriptional enhancers are frequently bound by a set of transcription factors that collaborate to activate lineage-specific gene expression. Recently, it was appreciated that a subset of enhancers comprise extended clusters dubbed stretch- or super-enhancers (SEs). These SEs are located near key cell identity genes, and enriched for non-coding genetic variations associated with disease. Previously, SEs have been defined as having the highest density of Med1, Brd4 or H3K27ac by ChIP-seq. The histone acetyltransferase P300 has been used as a marker of enhancers, but little is known about its binding to SEs. RESULTS: We establish that P300 marks a similar SE repertoire in embryonic stem cells as previously reported using Med1 and H3K27ac. We also exemplify a role for SEs in mouse T helper cell fate decision. Similarly, upon activation of macrophages by bacterial endotoxin, we found that many SE-associated genes encode inflammatory proteins that are strongly up-regulated. These SEs arise from small, low-density enhancers in unstimulated macrophages. We also identified expression quantitative trait loci (eQTL) in human monocytes that lie within such SEs. In macrophages and Th17 cells, inflammatory SEs can be perturbed either genetically or pharmacologically thus revealing new avenues to target inflammation. CONCLUSIONS: Our findings support the notion that P300-marked SEs can help identify key nodes of transcriptional control during cell fate decisions. The SE landscape changes drastically during cell differentiation and cell activation. As these processes are crucial in immune responses, SEs may be useful in revealing novel targets for treating inflammatory diseases. PMID- 26546039 TI - Smartphone Apps for Schizophrenia: A Systematic Review. AB - BACKGROUND: There is increasing interest in using mobile technologies such as smartphones for improving the care of patients with schizophrenia. However, less is known about the current clinical evidence for the feasibility and effectiveness of smartphone apps in this population. OBJECTIVE: To review the published literature of smartphone apps applied for the care of patients with schizophrenia and other psychotic disorders. METHODS: An electronic database search of Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Allied and Complementary Medicine, Health and Psychosocial Instruments, PsycINFO, and Embase was conducted on May 24, 2015. All eligible studies were systematically reviewed, and proportional meta-analyses were applied to pooled data on recruitment, retention, and adherence to examine the overall feasibility of smartphone interventions for schizophrenia. RESULTS: Our search produced 226 results from which 7 eligible articles were identified, reporting on 5 studies of smartphone apps for patients with schizophrenia. All examined feasibility, and one assessed the preliminary efficacy of a smartphone intervention for schizophrenia. Study lengths varied between 6 and 130 days. Overall retention was 92% (95% CI 82-98%). Participants consistently used the smartphone apps on more than 85% of days during the study period, averaging 3.95 interactions per person per day. Furthermore, participants responded to 71.9% of automated prompts (95% CI 65.7-77.8%). Participants reported a range of potential benefits from the various interventions, and user experience was largely positive. CONCLUSIONS: Although small, the current published literature demonstrates strong evidence for the feasibility of using smartphones to enhance the care of people with schizophrenia. High rates of engagement and satisfaction with a broad range of apps suggest the nascent potential of this mobile technology. However, there remains limited data on the efficacy of such interventions. PMID- 26546040 TI - Isolation and analysis of discreet human prostate cellular populations. AB - The use of lineage tracing in transgenic mouse models has revealed an abundance of subcellular phenotypes responsible for maintaining prostate homeostasis. The ability to use fresh human tissues to examine the hypotheses generated by these mouse experiments has been greatly enhanced by technical advances in tissue processing, flow cytometry and cell culture. We describe in detail the optimization of protocols for each of these areas to facilitate research on solving human prostate diseases through the analysis of human tissue. PMID- 26546041 TI - GADD45a physically and functionally interacts with TET1. AB - DNA demethylation plays a central role during development and in adult physiology. Different mechanisms of active DNA demethylation have been established. For example, Growth Arrest and DNA Damage 45-(GADD45) and Ten-Eleven Translocation (TET) proteins act in active DNA demethylation but their functional relationship is unresolved. Here we show that GADD45a physically interacts--and functionally cooperates with TET1 in methylcytosine (mC) processing. In reporter demethylation GADD45a requires endogenous TET1 and conversely TET1 requires GADD45a. On GADD45a target genes TET1 hyperinduces 5-hydroxymethylcytosine (hmC) in the presence of GADD45a, while 5-formyl-(fC) and 5-carboxylcytosine (caC) are reduced. Likewise, in global analysis GADD45a positively regulates TET1 mediated mC oxidation and enhances fC/caC removal. Our data suggest a dual function of GADD45a in oxidative DNA demethylation, to promote directly or indirectly TET1 activity and to enhance subsequent fC/caC removal. PMID- 26546042 TI - Peptidic exenatide and herbal catalpol mediate neuroprotection via the hippocampal GLP-1 receptor/beta-endorphin pathway. AB - Both peptidic agonist exenatide and herbal agonist catalpol of the glucagon-like peptide-1 receptor (GLP-1R) are neuroprotective. We have previously shown that activation of spinal GLP-1Rs expresses beta-endorphin in microglia to produce antinociception. The aim of this study was to explore whether exenatide and catalpol exert neuroprotection via activation of the hippocampal GLP-1R/beta endorphin pathway. The rat middle cerebral artery occlusion model was employed, and the GLP-1R immunofluorescence staining and beta-endorphin measurement were assayed in the hippocampus and primary cultures of microglia, neurons and astrocytes. The immunoreactivity of GLP-1Rs on microglia in the hippocampus was upregulated after ischemia reperfusion. Intracerebroventricular (i.c.v.) injection of exenatide and catalpol produced neuroprotection in the rat transient ischemia/reperfusion model, reflected by a marked reduction in brain infarction size and a mild recovery in neurobehavioral deficits. In addition, i.c.v. injection of exenatide and catalpol significantly stimulated beta-endorphin expression in the hippocampus and cultured primary microglia (but not primary neurons or astrocytes). Furthermore, exenatide and catalpol neuroprotection was completely blocked by i.c.v. injection of the GLP-1R orthosteric antagonist exendin (9-39), specific beta-endorphin antiserum, and selective opioid receptor antagonist naloxone. Our results indicate, for the first time, that the neuroprotective effects of catalpol and exenatide are GLP-1R-specific, and that these effects are mediated by beta-endorphin expression probably in hippocampal microglia. We postulate that in contrast to the peripheral tissue, where the activation of GLP-1Rs in pancreas islet beta-cells causes secretion of insulin to perform glucoregulation, it leads to beta-endorphin expression in microglial cells to produce neuroprotection and analgesia in the central nervous system. PMID- 26546043 TI - p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling. AB - Pancreatic cancer (PC) remains a highly lethal malignancy due to its unusual chemoresistance and high aggressiveness. A subpopulation of pancreatic tumor cells, known as cancer stem cells (CSCs), is considered responsible not only for tumor-maintenance, but also for its widespread metastasis and therapeutic failure. Here we investigated the role of p-21 activated kinase 4 (PAK4) in driving PC stemness properties. Our data demonstrate that triple-positive (CD24(+)/CD44(+)/EpCAM(+)) subpopulation of pancreatic CSCs exhibits greater level of PAK4 as compared to triple-negative (CD24(-)/CD44(-)/EpCAM(-)) cells. Moreover, PAK4 silencing in PC cells leads to diminished fraction of CD24, CD44, and EpCAM positive cells. Furthermore, we show that PAK4-silenced PC cells exhibit decreased sphere-forming ability and increased chemosensitivity to gemcitabine toxicity. PAK4 expression is also associated with enhanced levels of stemness-associated transcription factors (Oct4/Nanog/Sox2 and KLF4). Furthermore, our data show decreased nuclear accumulation and transcriptional activity of STAT3 in PAK4-silenced PC cells and restitution of its activity leads to restoration of stem cell phenotypes. Together, our findings deliver first experimental evidence for the involvement of PAK4 in PC stemness and support its clinical utility as a novel therapeutic target in PC. PMID- 26546044 TI - Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib. AB - Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib. Sorafenib dramatically reduced the levels of AFP produced by HCC cells independently of its effect on cell viability. The mRNA levels of AFP decreased upon sorafenib treatment, while the AFP protein remained localized in the Golgi apparatus. Sorafenib activated the Regulated Inositol-Requiring Enzyme 1alpha (IRE-1alpha) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1alpha partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib. The findings provide new insights on the regulation of AFP, and identify it as a biomarker suitable for the exploration of HCC cell proteostasis in the context of therapeutic targeting. PMID- 26546045 TI - The bone marrow niche in support of breast cancer dormancy. AB - Despite the success in detecting breast cancer (BC) early and, with aggressive therapeutic intervention, BC remains a clinical problem. The bone marrow (BM) is a favorable metastatic site for breast cancer cells (BCCs). In BM, the survival of BCCs is partly achieved by the supporting microenvironment, including the presence of immune suppressive cells such as mesenchymal stem cells (MSCs). The heterogeneity of BCCs brings up the question of how each subset interacts with the BM microenvironment. The cancer stem cells (CSCs) survive in the BM as cycling quiescence cells and, forming gap junctional intercellular communication (GJIC) with the hematopoietic supporting stromal cells and MSCs. This type of communication has been identified close to the endosteum. Additionally, dormancy can occur by soluble mediators such as cytokines and also by the exchange of exosomes. These latter mechanisms are reviewed in the context of metastasis of BC to the BM for transition as dormant cells. The article also discusses how immune cells such as macrophages and regulatory T-cells facilitate BC dormancy. The challenges of studying BC dormancy in 2-dimensional (2-D) system are also incorporated by proposing 3-D system by engineering methods to recapitulate the BM microenvironment. PMID- 26546046 TI - TMPRSS4 induces cancer stem cell-like properties in lung cancer cells and correlates with ALDH expression in NSCLC patients. AB - Metastasis involves a series of changes in cancer cells that promote their escape from the primary tumor and colonization to a new organ. This process is related to the transition from an epithelial to a mesenchymal phenotype (EMT). Recently, some authors have shown that migratory cells with an EMT phenotype share properties of cancer stem cells (CSCs), which allow them to form a new tumor mass. The type II transmembrane serine protease TMPRSS4 is highly expressed in some solid tumors, promotes metastasis and confers EMT features to cancer cells. We hypothesized that TMPRSS4 could also provide CSC properties. Overexpression of TMPRSS4 reduces E-cadherin and induces N-cadherin and vimentin in A549 lung cancer cells, supporting an EMT phenotype. These changes are accompanied by enhanced migration, invasion and tumorigenicity in vivo. TMPRSS4 expression was highly increased in a panel of lung cancer cells cultured as tumorspheres (a typical assay to enrich for CSCs). H358 and H441 cells with knocked-down TMPRSS4 levels were significantly less able to form primary and secondary tumorspheres than control cells. Moreover, they showed a lower proportion of ALDH+ cells (examined by FACS analysis) and lower expression of some CSC markers than controls. A549 cells overexpressing TMPRSS4 conferred the opposite phenotype and were also more sensitive to the CSC-targeted drug salinomycin than control cells, but were more resistant to regular chemotherapeutic drugs (cisplatin, gemcitabine and 5-fluorouracil). Analysis of 70 NSCLC samples from patients revealed a very significant correlation between TMPRSS4 expression and CSC markers ALDH (p = 0.0018) and OCT4 (p = 0.0004), suggesting that TMPRSS4 is associated with a CSC phenotype in patients' tumors. These results show that TMPRSS4, in addition to inducing EMT, can also promote CSC features in lung cancer; therefore, CSC targeting drugs could be an appropriate treatment for TMPRSS4+ tumors. PMID- 26546047 TI - Candidate DNA repair susceptibility genes identified by exome sequencing in high risk pancreatic cancer. AB - The genetic basis underlying the majority of hereditary pancreatic adenocarcinoma (PC) is unknown. Since DNA repair genes are widely implicated in gastrointestinal malignancies, including PC, we hypothesized that there are novel DNA repair PC susceptibility genes. As germline DNA repair gene mutations may lead to PC subtypes with selective therapeutic responses, we also hypothesized that there is an overall survival (OS) difference in mutation carriers versus non-carriers. We therefore interrogated the germline exomes of 109 high-risk PC cases for rare protein-truncating variants (PTVs) in 513 putative DNA repair genes. We identified PTVs in 41 novel genes among 36 kindred. Additional genetic evidence for causality was obtained for 17 genes, with FAN1, NEK1 and RHNO1 emerging as the strongest candidates. An OS difference was observed for carriers versus non carriers of PTVs with early stage (<=IIB) disease. This adverse survival trend in carriers with early stage disease was also observed in an independent series of 130 PC cases. We identified candidate DNA repair PC susceptibility genes and suggest that carriers of a germline PTV in a DNA repair gene with early stage disease have worse survival. PMID- 26546049 TI - Global environmental change effects on ecosystems: the importance of land-use legacies. AB - One of the major challenges in ecology is to predict how multiple global environmental changes will affect future ecosystem patterns (e.g. plant community composition) and processes (e.g. nutrient cycling). Here, we highlight arguments for the necessary inclusion of land-use legacies in this endeavour. Alterations in resources and conditions engendered by previous land use, together with influences on plant community processes such as dispersal, selection, drift and speciation, have steered communities and ecosystem functions onto trajectories of change. These trajectories may be modulated by contemporary environmental changes such as climate warming and nitrogen deposition. We performed a literature review which suggests that these potential interactions have rarely been investigated. This crucial oversight is potentially due to an assumption that knowledge of the contemporary state allows accurate projection into the future. Lessons from other complex dynamic systems, and the recent recognition of the importance of previous conditions in explaining contemporary and future ecosystem properties, demand the testing of this assumption. Vegetation resurvey databases across gradients of land use and environmental change, complemented by rigorous experiments, offer a means to test for interactions between land-use legacies and multiple environmental changes. Implementing these tests in the context of a trait-based framework will allow biologists to synthesize compositional and functional ecosystem responses. This will further our understanding of the importance of land-use legacies in determining future ecosystem properties, and soundly inform conservation and restoration management actions. PMID- 26546048 TI - Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review. AB - BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area. PMID- 26546050 TI - Quadriceps performance under activation of foot dorsal extension in healthy volunteers: an interventional cohort study. AB - BACKGROUND: The m. quadriceps femoris is the strongest muscle in the human body and plays an important role in sports, activities of daily living and independence. Two older studies showed increased electromyographic (EMG) activity of the quadriceps when the dorsal extensors of the foot were pre-activated. The aim was to physiologically replicate this finding by EMG and to verify it functionally by single leg hop. METHODS: EMG activity (root mean square, RMS) was tested on the leg press at the isometric load of the individual 12-repetition maximum (12RM) weight (on average 79.7 kg) at 45 degrees and 90 degrees knee flexion. Single leg hop distance was measured between the tests. Intra-individual changes between with and without dorsal foot extension were quantified and compared by standardized response means (SRM). RESULTS: Thirty-five healthy subjects between 21 and 57 years were included. The m. vastus medialis was activated on average to an RMS of 32.4 MUV without and 53.7 MUV with dorsal foot extension (SRM = 1.39, p < 0.001) at 45 degrees knee flexion and an RMS of 124.9 MUV versus 152.8 MUV (SRM = 1.08, p < 0.001) at 90 degrees . The corresponding data for the rectus femoris were 9.4 MUV versus 18.9 MUV (SRM = 0.71, p < 0.001) at 45 degrees and 77.8 MUV versus 135.3 MUV (SRM = 0.89, p < 0.001) at 90 degrees . Mean single leg hop distance was 169.8 cm without versus 178.9 cm with dorsal foot extension (SRM = 1.09, p < 0.001). CONCLUSIONS: Pre-activation of dorsal foot extensors significantly increased EMG activity in the m. quadriceps femoris and single leg hop distance. It can therefore be used to improve functional quadriceps muscle performance and knee joint stability in training and rehabilitation. PMID- 26546051 TI - Triamcinolone during pars plana vitrectomy for open globe trauma: a pilot randomised controlled clinical trial. AB - PURPOSE: To investigate the feasibility of conducting a randomised controlled trial in patients undergoing pars plana vitrectomy surgery following open globe trauma (OGT). Additionally, to investigate the treatment effect and toxicity of intensive anti-inflammatory agents. METHODS: A 2-year, pilot, single-centre prospective, participant and surgeon-masked randomised controlled trial (RCT). Forty patients requiring vitrectomy surgery following OGT were randomised to either standard (control) or study treatment (adjuncts) in a 1:1 allocation ratio. Perioperatively, the adjunct group received intravitreal and subtenons triamcinolone acetonide, oral flurbiprofen and guttae prednisolone acetate 1%. The control group received standard care. Primary outcome was anatomical success at 6 months. Secondary outcomes included final visual acuity, occurrence of proliferative vitreoretinopathy, intraocular pressure rise, number of operations and recruitment rate. RESULTS: 40 patients were recruited within 21 months. Primary outcome assessment showed similar results in anatomical success with 50% (10/20) in the adjunct group compared with 47% (9/19) in the standard group (OR 1.11, 95% CI 0.316 to 3.904). Visual outcomes were better in the adjunct group with a final median visual acuity of 31 Early Treatment Diabetic Retinopathy Study (ETDRS) letters compared with 25 ETDRS letters in the standard group. A higher proportion of patients gained 10, 20 and 30 ETDRS letters in the adjunct group (80%, 65% and 50%, respectively) compared with the standard group (52.6%, 52.6% and 42.1%). Fewer adjunct patients (15%, n=3) had poor visual outcomes (Zero ETDRS letters) compared with 42.1%, (n=8). CONCLUSIONS: An RCT in this population is deliverable and estimated recruitment rates are realistic. Results and patient discussions determined that the definitive study should have vision as a primary outcome. This pilot study is supportive of there being a positive treatment effect of intensive anti-inflammatory agents in OGT. TRIAL REGISTRATION NUMBER: European Clinical Trials Database 2007-005138-35; Results. PMID- 26546052 TI - Feeding practices and nutrient content of complementary meals in rural central Tanzania: implications for dietary adequacy and nutritional status. AB - BACKGROUND: Stunting and micronutrient deficiencies are significant health problems among infants and young children in rural Tanzania. Objective of the study was to assess feeding practices, nutrient content of complementary meals, and their implications for dietary adequacy and nutritional status. METHODS: A cross-sectional study was conducted in six randomly selected villages in Mpwapwa District, Tanzania during the post-harvest season. Information on feeding practices, dietary consumption and anthropometric measurements of all infants below the age of one year were collected. Forty samples of common meals were collected and analysed for proximate composition, iron, zinc and calcium. Results were expressed per 100 g dry weight. RESULTS: Energy, protein and fat content in porridge ranged from 40.67-63.92 kcal, 0.54-1.74% and 0.30-2.12%, respectively. Iron, zinc and calcium contents (mg/100 g) in porridge were 0.11-2.81, 0.10-3.23, and 25.43-125.55, respectively. Median portion sizes were small (porridge: 150 350 g; legumes and meats: 39-90 g). Very few children (6.67%) consumed animal source foods. Low meal frequency, low nutrient content, small portion size and limited variety reduced the contribution of meals to daily nutritional needs. CONCLUSIONS: Findings of the study highlight inadequate feeding practices, low nutritional quality of meals and high prevalence of stunting. Feasible strategies are needed to address the dietary inadequacies and chronic malnutrition of rural infants. PMID- 26546053 TI - Primary jejunal gastrinoma: a case report and review of the literature. AB - BACKGROUND: Primary jejunal gastrinomas are exceedingly rare, and data for long term follow-up is limited. Until now, only six cases of gastrinomas arising from the jejunum have been reported in the English literature. CASE PRESENTATION: Presented is a case of a primary gastrinoma located in the proximal jejunum. After surgical resection of the tumor, eugastrinemia was quickly achieved and after a 10-year follow-up period, the patient was still disease-free. CONCLUSIONS: This case report demonstrates that surgical resection of a primary jejunal gastrinoma without evidence of metastasis can be curative, with a good long-term prognosis. PMID- 26546054 TI - Adding value to plant oils and fatty acids: Biological transformation of fatty acids into omega-hydroxycarboxylic, alpha,omega-dicarboxylic, and omega aminocarboxylic acids. AB - Not only short chain omega-hydroxycarboxylic acids, alpha,omega-dicarboxylic acids, and omega-aminocarboxylic acids but also medium to long chain carboxylic acids are widely used as building blocks and intermediates in the chemical, pharmaceutical, and food industries. Thereby, recent achievements in biological production of medium to long chain carboxylic acids are addressed here. omega Hydroxycarboxylic and alpha,omega-dicarboxylic acids were synthesized via terminal CH bond oxygenation of fatty acids and/or internal oxidative cleavage of the fatty acid carbon skeletons. omega-Aminocarboxylic acids were enzymatically produced from omega-hydroxycarboxylic acids via omega-oxocarboxylic acids. Productivities and product yields of some of the products are getting close to the industrial requirements for large scale production. PMID- 26546055 TI - Quantitative image analysis as a tool for Yarrowia lipolytica dimorphic growth evaluation in different culture media. AB - Yarrowia lipolytica, a yeast strain with a huge biotechnological potential, capable to produce metabolites such as gamma-decalactone, citric acid, intracellular lipids and enzymes, possesses the ability to change its morphology in response to environmental conditions. In the present study, a quantitative image analysis (QIA) procedure was developed for the identification and quantification of Y. lipolytica W29 and MTLY40-2P strains dimorphic growth, cultivated in batch cultures on hydrophilic (glucose and N-acetylglucosamine (GlcNAc) and hydrophobic (olive oil and castor oil) media. The morphological characterization of yeast cells by QIA techniques revealed that hydrophobic carbon sources, namely castor oil, should be preferred for both strains growth in the yeast single cell morphotype. On the other hand, hydrophilic sugars, namely glucose and GlcNAc caused a dimorphic transition growth towards the hyphae morphotype. Experiments for gamma-decalactone production with MTLY40-2P strain in two distinct morphotypes (yeast single cells and hyphae cells) were also performed. The obtained results showed the adequacy of the proposed morphology monitoring tool in relation to each morphotype on the aroma production ability. The present work allowed establishing that QIA techniques can be a valuable tool for the identification of the best culture conditions for industrial processes implementation. PMID- 26546056 TI - Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. AB - BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy among men. The Discovery of new agents for the treatment of prostate cancer is urgently needed. Compound WZ35, a novel analog of the natural product curcumin, exhibited good anti-prostate cancer activity, with an IC50 of 2.2 MUM in PC-3 cells. However, the underlying mechanism of WZ35 against prostate cancer cells is still unclear. METHODS: Human prostate cancer PC-3 cells and DU145 cells were treated with WZ35 for further proliferation, apoptosis, cell cycle, and mechanism analyses. NAC and CHOP siRNA were used to validate the role of ROS and ER stress, respectively, in the anti-cancer actions of WZ35. RESULTS: Our results show that WZ35 exhibited much higher cell growth inhibition than curcumin by inducing ER stress-dependent cell apoptosis in human prostate cells. The reduction of CHOP expression by siRNA partially abrogated WZ35-induced cell apoptosis. WZ35 also dose-dependently induced cell cycle arrest in the G2/M phase. Furthermore, we found that WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells. Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35. CONCLUSIONS: Taken together, this work presents the novel anticancer candidate WZ35 for the treatment of prostate cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human prostate cancer treatment. PMID- 26546057 TI - Physiological effects of compensatory growth during the larval stage of the ladybird, Cryptolaemus montrouzieri. AB - The growth rate of insects may vary in response to shifty environments. They may achieve compensatory growth after a period of food restriction followed by ad libitum food, which may further affect the reproductive performance and lifespan of the resulting phenotypes. However, little is known about the physiological mechanisms associated with such growth acceleration in insects. The present study examined the metabolic rate, the antioxidant enzyme activity and the gene expression of adult Cryptolaemus montrouzieri (Coleoptera: Coccinellidae) after experiencing compensatory growth during its larval stages. Starved C. montrouzieri individuals achieved a similar developmental time and adult body mass as those supplied with ad libitum food during their entire larval stage, indicating that compensatory growth occurred as a result of the switch in larval food regime. Further, the compensatory growth was found to exert effects on the physiological functions of C. montrouzieri, in terms of its metabolic rates and enzyme activities. The adults undergoing compensatory growth were characterized by a higher metabolic rate, a lower activity of the antioxidant enzymes glutathione reductase, catalase, and superoxide dismutase and a lower gene expression of P450 and trehalase. Taken together, the results indicate that although compensatory growth following food restriction in early larval life prevents developmental delay and body mass loss, the resulting adults may encounter physiological challenges affecting their fitness. PMID- 26546058 TI - Protective effect of TSLP delivered at the gut mucosa level by recombinant lactic acid bacteria in DSS-induced colitis mouse model. AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a cytokine known to mature dendritics cells, lower pro-inflammatory IL-12 secretion, induce differentiation of anti-inflammatory FoxP3+ regulatory T cells (Treg). Moreover, Crohn's disease patients have shown a reduction of intestinal TSLP expression. To understand the role of TSLP in inflammation, we constructed Lactococcus lactis strain producing TSLP (LL-TSLP) and investigated the effect of its administration on dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: LL-TSLP secrete an active molecule which lowers secretion of IL-12 by dendritic cells. Treatment with LL-TSLP, increases the amount of TGF-beta secreted by T cells in Mesenteric Lymph Node in healthy mice. In acute DSS-induced colitis, LL-TSLP delayed the Disease Activity Index and lowered histological score and colonic INF-gamma production. In a DSS-recovery model, LL-TSLP induced a better protective effect if the strain was administered at the beginning of the colitis. At Day 4 of colitis we observed an induction of Treg by LL-TSLP. CONCLUSIONS: TSLP showed an anti-inflammatory protective role in DSS-induced colitis. We have demonstrated that a short and early administration of LL-TSLP is more efficient than a long lasting treatment. PMID- 26546059 TI - The management and treatment of children with Fabry disease: A United States based perspective. AB - Fabry disease is an inherited X-linked disorder that presents during childhood in male and female patients. Young patients may initially experience pain, hypohidrosis, and gastrointestinal symptoms. Other manifestations of Fabry disease, such as renal and cardiac disease, manifest later in adolescence or adulthood. In the pediatric population, renal damage is typically subclinical and identifiable only through biopsy. Specialists from the United States with expertise in Fabry disease convened during 2013-2014 in order to develop these consensus guidelines about the management and treatment of children with Fabry disease. The presence of symptoms in boys and girls of any age is an indication to begin therapy. Early treatment before the onset of potentially irreversible vital organ pathology is ideal. Asymptomatic children with Fabry mutations should be followed closely for the development of renal, cardiac, neurological, or gastrointestinal signs, symptoms, or laboratory changes, which would warrant treatment initiation. A comprehensive care plan should be implemented by the treating physicians to guide the management of children with Fabry disease. PMID- 26546060 TI - Serum sclerostin levels, arteriovenous fistula calcification and 2-years all cause mortality in prevalent hemodialysis patients. AB - BACKGROUND: Bone and mineral abnormalities, and cardiovascular calcification are associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). Recent studies have implicated Wnt signaling pathway in the pathogenesis of bone metabolism and vascular calcification. Sclerostin is a soluble inhibitor of Wnt signaling pathway and has been shown to be associated with decreased bone turnover and vascular calcification in CKD patients. OBJECTIVES: The aim was to investigate whether the circulating levels of sclerostin are associated with all-cause mortality in prevalent hemodialysis patients. METHODS: Data are prospectively collected for 24 months for survival analysis in 350 prevalent hemodialysis patients. At baseline, serum sclerostin levels were measured and arteriovenous fistula calcification was detected by using a 64-detector computerized tomographic scanner. RESULTS: During the follow up, 84 (24%) patients died. Patients who died had higher serum sclerostin levels. Kaplan-Meier curve revealed that patients with increasing tertiles of serum sclerostin levels at baseline, had a worse survival. In the multivariate Cox regression analysis age, albumin, and presence of arteriovenous fistula calcification, but not sclerostin levels, were found to be independent predictors of survival in maintenance hemodialysis patients. CONCLUSION: Further clinical studies with longer follow-up are needed to clarify the impact of serum sclerostin levels on morbidity and mortality of maintenance hemodialysis patients. CLINICAL TRIAL REGISTRATION NUMBER: The study was performed as a post hoc survival analysis of the patients involved in a single-center prospective trial investigating the association between serum sclerostin levels and arteriovenous fistula calcification and patency [Balci M, et al. Herz 2015;40:289 97] with a Clinicaltrials.gov number: NCT01382966. PMID- 26546061 TI - Surgical repair of inferior sinus venosus defects: a novel approach with unsnared inferior vena cava. AB - BACKGROUND: Inferior sinus venosus defects (SVD) are very rare and difficult to image from transthoracic echocardiography. Surgical errors were occasionally reported in the repair of inferior SVDs. RESULTS: The authors have operated on 12 inferior SVD patients using bicaval cannulation with unsnared inferior vena cava (IVC) and proved successful. CONCLUSION: This technique guaranteed a better exposure of surgical field and facilitate identifying the anatomical relationship between lower part of the SVD and IVC orifice, thus avoiding postoperative IVC - left atrial shunt and other surgical mistakes. PMID- 26546062 TI - T cell deficiency in spinal cord injury: altered locomotor recovery and whole genome transcriptional analysis. AB - BACKGROUND: T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T cell-deficient athymic nude (AN) rats exhibit improved functional recovery when compared to immunocompetent Sprague-Dawley (SD) rats following spinal cord transection. METHODS: In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery. RESULTS: Athymic nude rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for T(h)2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate. CONCLUSIONS: We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue. PMID- 26546063 TI - Acetabular reconstruction with a reinforcement device and bone grafting in revision arthroplasty-a mean five years of follow-up. AB - PURPOSE: To evaluate the clinical and radiological outcomes of acetabular reconstruction using a reinforcement device (RD) in combination with bone grafting in Paprosky type 2 and 3 acetabular bone defects. METHODS: Morselised bone grafts were used to fill cavitary defects and a structural graft placed in the superior part of the acetabulum in cases of cranial bone defects, with a proximally fixed RD (Protetim, Hodmezovasarhely, Hungary) implanted in all cases. Construct stability, device positioning, hip centre of rotation and medial acetabular wall thickness were evaluated radiologically. Survival rates were estimated with aseptic loosening and revision for any reason as endpoints. RESULTS: The 28 patients (29 hips) were followed for 4.8 +/- 2.7 years (range, 2 10.4 years). Hip centre of rotation was lowered in all cases, with no significant differences between the mean values obtained post-operatively and at the last follow-up. Medial acetabular wall thickness and RD abduction angle were maintained up to the last evaluation. Bone grafts integrated by two years post operatively in the majority of cases. Kaplan-Meier survival rates were 85.2 % and 82.1 % for the two endpoints at ten years. CONCLUSIONS: Acetabular reconstruction using a proximally fixed RD in combination with bone grafting offered good mid term results in the treatment of acetabular bone defects. In cases of severe bone loss, the structural allograft allowed placement of the RD with ischial contact, rendering survival rates similar to RDs with both iliac and ilioischial fixation. The technique was successful in restoring and maintaining medial acetabular bone stock and construct stability for up to ten years. PMID- 26546064 TI - Management of congenital pseudarthrosis of the tibia with the Ilizarov method in a paediatric population: influence of aetiological factors. AB - PURPOSE: Our study compared the rates of union achieved with the Ilizarov method in congenital pseudarthrosis of the tibia (CPT) associated with neurofibromatosis type 1 (NF1) or CPT of idiopathic origin in paediatric patients. METHODS: We studied the outcomes of 28 children that were treated for CPT between 2005 and 2013. Group 1 included children (n = 14, mean age = 9.7 years) with CPT associated with NF1 while group 2 were CPT cases that had radiographic confirmation of dysplastic lesions in the tibia but lacked clinical NF1 manifestations (n = 14, mean age = 8.6 years). There was no statistical difference between the groups regarding their age or number of previous operations per patient. Individual technical solutions were planned for each patient but coaptation of bone fragments and autologous local tissue grafting to achieve a greater bone thickness and contact area at the pseudarthrosis level were mainly used. Refracture-free rate after the first operation, number of re operations per patient, and union rates in the groups were compared. RESULTS: Bone union and weight bearing were obtained in all the cases after the first operation. Refracture-free rate was 42.86 % in group 1 and 35.71% in group 2 (no statistical difference, p > 0.05). Mean number of re-operations per patient was 1.07 and 0.78 respectively (p > 0.05). Subsequent treatment for refractures with the Ilizarov techniques gained 92.86% of union in both groups at the follow-ups by completion of the study (range, 2-9 years). CONCLUSIONS: The Ilizarov method yields comparable results in the management of CPT associated with NF1 or tibial dysplasia of idiopathic origin in paediatric cases. Further research should focus on the ways to support the Ilizarov method in order to reduce the number of repetitive surgeries or eliminate them. PMID- 26546065 TI - Pulmonary Vein Stenosis After Ablation: The Difference Between Clinical Symptoms and Imaging Findings, and the Importance of Definitions in This Context. PMID- 26546066 TI - "Watching time tick by...": Decision making for Duchenne muscular dystrophy trials. AB - OBJECTIVE: This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. METHODS: Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. RESULTS: Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. CONCLUSIONS: The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. PMID- 26546067 TI - Adult Congenital Heart Disease-Coping And REsilience (ACHD-CARE): Rationale and methodology of a pilot randomized controlled trial. AB - INTRODUCTION: One-third of North American adults with congenital heart disease (CHD) have diagnosable mood or anxiety disorders and most do not receive mental health treatment. There are no published interventions targeting the psychosocial needs of patients with CHD of any age. We describe the development of a group psychosocial intervention aimed at improving the psychosocial functioning, quality of life, and resilience of adults with CHD and the design of a study protocol to determine the feasibility of a potential full-scale randomized controlled trial (RCT). METHODS/DESIGN: Drawing upon our quantitative and qualitative research, we developed the Adult CHD-Coping And REsilience (ACHD CARE) intervention and designed a feasibility study that included a 2-parallel arm non-blinded pilot RCT. Eligible participants (CHD, age >= 18 years, no planned surgery, symptoms suggestive of a mood and/or anxiety disorder) were randomized to the ACHD-CARE intervention or Usual Care (1:1 allocation ratio). The group intervention was delivered during eight 90-minute weekly sessions. Feasibility will be assessed in the following domains: (i) process (e.g. recruitment and retention), (ii) resources, (iii) management, (iv) scientific outcomes, and (v) intervention acceptability. DISCUSSION: This study underscores the importance of carefully developing and testing the feasibility of psychosocial interventions in medical populations before moving to full-scale clinical trials. At study conclusion, we will be poised to make one of three determinations for a full-scale RCT: (1) feasible, (2) feasible with modifications, or (3) not feasible. This study will guide the future evaluation and provision of psychosocial treatment for adults with CHD. PMID- 26546068 TI - Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology. AB - AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS: ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ~ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3 4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION: Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129. PMID- 26546069 TI - Development and evaluation of a Loop Mediated Isothermal Amplification (LAMP) technique for the detection of hookworm (Necator americanus) infection in fecal samples. AB - BACKGROUND: Hookworm infection is a major concern in sub-Saharan Africa, particularly in children and pregnant women. Necator americanus and Ancylostoma duodenale are responsible for this condition. Hookworm disease is one of the Neglected tropical diseases (NTDs) that are targeted for elimination through global mass chemotherapy. To support this there is a need for reliable diagnostic tools. The conventional diagnostic test, Kato-Katz that is based on microscopic detection of parasite ova in faecal samples, is not effective due to its low sensitivity that is brought about mainly by non-random distribution of eggs in stool and day to day variation in egg output. It is tedious, cumbersome to perform and requires experience for correct diagnosis. LAMP-based tests are simple, relatively cheap, offer greater sensitivity, specificity than existing tests, have high throughput capability, and are ideal for use at the point of care. METHODS: We have developed a LAMP diagnostic test for detection of hookworm infection in faecal samples. LAMP relies on auto cycling strand displacement DNA synthesis performed at isothermal temperature by Bst polymerase and a set of 4 specific primers. The primers used in the LAMP assay were based on the second Internal Transcribed Spacer (ITS-2) region and designed using Primer Explorer version 4 Software. The ITS-2 region of the ribosomal gene (rDNA) was identified as a suitable target due to its low mutation rates and substantial differences between species. DNA was extracted directly from human faecal samples, followed by LAMP amplification at isothermal temperature of 63 degrees C for 1 h. Amplicons were visualized using gel electrophoresis and SYBR green dye. Both specificity and sensitivity of the assay were determined. RESULTS: The LAMP based technique developed was able to detect N. americanus DNA in faecal samples. The assay showed 100 % specificity and no cross-reaction was observed with other helminth parasites (S. mansoni, A. lumbricoides or T. trichiura). The developed LAMP assay was 97 % sensitive and DNA at concentrations as low as 0.4 fg were amplified. CONCLUSION: The LAMP assay developed is an appropriate diagnostic method for the detection of N. americanus DNA in human stool samples because of its simplicity, low cost, sensitivity, and specificity. It holds great promise as a useful diagnostic tool for use in disease control where infection intensities have been significantly reduced. PMID- 26546070 TI - Tarsal tunnel syndrome-A narrative literature review. AB - BACKGROUND: Tarsal tunnel syndrome is classified as a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches individually or collectively. The tunnel courses deep to fascia, the flexor retinaculum and within the abductor hallucis muscle of the foot/ankle. The condition is rare and regularly under-diagnosed leading to a range of symptoms affecting the plantar margins of the foot. There are many intervention strategies for treating tarsal tunnel syndrome with limited robust evidence to guide the clinical management of this condition. The role of conservative versus surgical interventions at various stages of the disease process remains unclear, and there is a need for a structured, step-wise approach in treating patients with this syndrome based on derived empirical evidence. This narrative review attempts to scrutinize the literature to date by clarifying initial presentation, investigations and definitive treatment for the purpose of assisting future informed clinical decision and prospective research endeavours. PROCESS: The literature searches that have been incorporated in compiling a rigorous review of this condition have included: the Cochrane Neuromuscular Group's Specialized Register (Cochrane Library 2013), the databases of EMBASE, AMED, MEDLINE, CINAHL, Physiotherapy evidence database (PEDRO), Biomed Central, Science Direct and Trip Database (1972 to the present). Reference listings of located articles were also searched and scrutinized. Authors and experts within the field of lower-limb orthopaedics were contacted to discuss applicable data. Subject-specific criteria searches utilizing the following key terms were performed across all databases: tarsal tunnel syndrome, tibial neuralgia, compression neuropathy syndromes, tibial nerve impingement, tarsal tunnel neuropathy, entrapment tibial nerve, posterior tibial neuropathy. These search strategies were modified with differing databases, adopting specific sensitivity-searching tools and functions unique to each. This search strategy identified 88 journal articles of relevance for this narrative literature review. FINDINGS: This literature review has appraised the clinical significance of tarsal tunnel syndrome, whilst assessing varied management interventions (non-surgical and surgical) for the treatment of this condition in both adults and children. According to our review, there is limited high-level robust evidence to guide and refine the clinical management of tarsal tunnel syndrome. Requirements for small-scaled randomized controlled trials in groups with homogenous aetiology are needed to analyse the effectiveness of specific treatment modalities. CONCLUSIONS: It is necessary that further research endeavours be pursued for the clinical understanding, assessment and treatment of tarsal tunnel syndrome. Accordingly, a structured approach to managing patients who have been correctly diagnosed with this condition should be formulated on the basis of empirical evidence where possible. PMID- 26546071 TI - Metabolic Syndrome and Prostate Cancer: a Review of Complex Interplay Amongst Various Endocrine Factors in the Pathophysiology and Progression of Prostate Cancer. AB - The human prostate gland is an endocrine organ where dysregulation of various hormonal factors may play a pivotal role in the pathogenesis of prostate cancer. There is emerging epidemiological data to support the role of components of metabolic syndrome, namely, obesity, hypercholesterolaemia, diabetes and hyperinsulinaemia on the development and/or the progression of prostate cancer. Although the exact mechanisms behind the relationship between metabolic syndrome and prostate cancer remain largely unknown, various in vitro and animal experiments of metabolic syndrome models have been shown to promote survival, mitogenesis, metastasis and treatment resistance pathways, through various adaptive responses such as intracellular steroidogenesis and lipogenesis. Also, in a large proportion of men with metabolic syndrome, alteration in levels of hormones such as testosterone, leptin and adiponectin has been shown to contribute towards the aggression of prostate cancer. Whilst the exact bio pathophysiological mechanisms between metabolic syndrome and prostate cancer are yet to be fully elucidated, medications that target specific components of metabolic syndrome have further provided evidence for the inter-relationship between metabolic syndrome, its components and prostate cancer. Emerging in vitro and molecular data is likely to bring us closer to utilizing this knowledge to target particular cancer survival pathways and improving outcomes for men with prostate cancer. PMID- 26546072 TI - Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan. AB - PURPOSE: To validate and compare the values of "MIC" and "trifecta" as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN. METHODS: We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow up renal scan 3-6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta. RESULTS: Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B -1.8 (-2.7, -0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation. CONCLUSIONS: Achievement of both MIC and "trifecta" is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney. PMID- 26546073 TI - Prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome: a meta-analysis. AB - PURPOSE: This study aims to estimate the prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) by conducting a meta-analysis. METHODS: Relevant publications were searched using PubMed, Embase, CBM, China National Knowledge Infrastructure, VIP and Wanfang databases up to August 2015. Studies that reported the prevalence of erectile dysfunction, premature ejaculation and total sexual dysfunction in men with CP/CPPS were included. RESULTS: A total of 24 studies involving 11,189 men were included. Overall prevalence of sexual dysfunction in men with CP/CPPS was 0.62 (95 % CI 0.48-0.75), while the prevalence of erectile dysfunction and premature ejaculation was 0.29 (95 % CI 0.24-0.33) and 0.40 (95 % CI 0.30-0.50), respectively. From 1999 to 2010, the prevalence of sexual dysfunction, erectile dysfunction and premature ejaculation was 0.65 (95 % CI 0.45-0.83), 0.27 (95 % CI 0.22-0.33) and 0.41 (95 % CI 0.27-0.55), respectively. From 2011 to 2014, the prevalence of sexual dysfunction, erectile dysfunction and premature ejaculation was 0.50 (95 % CI 0.22-0.75), 0.35 (95 % CI 0.29- 0.40) and 0.39 (95 % CI 0.37 0.41), respectively. CONCLUSION: The prevalence of sexual dysfunction in men with CP/CPPS was high, even though overall sexual dysfunction demonstrated a slightly decreasing trend. Furthermore, erectile dysfunction prevalence rate had an increasing trend in recent years. More prospective studies are needed to evaluate sexual dysfunction improvement with better management of CP/CPPS. PMID- 26546074 TI - Review of recent advances in segmentation of the breast boundary and the pectoral muscle in mammograms. AB - This paper presents a review of recent advances in the development of methods for segmentation of the breast boundary and the pectoral muscle in mammograms. Regardless of improvement of imaging technology, accurate segmentation of the breast boundary and detection of the pectoral muscle are still challenging tasks for image processing algorithms. In this paper, we discuss problems related to mammographic image preprocessing and accurate segmentation. We review specific methods that were commonly used in most of the techniques proposed for segmentation of mammograms and discuss their advantages and disadvantages. Comparative analysis of the methods reported on is made difficult by variations in the datasets and procedures of evaluation used by the authors. We attempt to overcome some of these limitations by trying to compare methods which used the same dataset and have some similarities in approaches to the breast boundary segmentation and detection of the pectoral muscle. In this paper, we will address the most often used methods for segmentation such as thresholding, morphology, region growing, active contours, and wavelet filtering. These methods, or their combinations, are the ones most used in the last decade by the majority of work published in this image processing domain. PMID- 26546075 TI - A review of presented mathematical models in Parkinson's disease: black- and gray box models. AB - Parkinson's disease (PD), one of the most common movement disorders, is caused by damage to the central nervous system. Despite all of the studies on PD, the formation mechanism of its symptoms remained unknown. It is still not obvious why damage only to the substantia nigra pars compacta, a small part of the brain, causes a wide range of symptoms. Moreover, the causes of brain damages remain to be fully elucidated. Exact understanding of the brain function seems to be impossible. On the other hand, some engineering tools are trying to understand the behavior and performance of complex systems. Modeling is one of the most important tools in this regard. Developing quantitative models for this disease has begun in recent decades. They are very effective not only in better understanding of the disease, offering new therapies, and its prediction and control, but also in its early diagnosis. Modeling studies include two main groups: black-box models and gray-box models. Generally, in the black-box modeling, regardless of the system information, the symptom is only considered as the output. Such models, besides the quantitative analysis studies, increase our knowledge of the disorders behavior and the disease symptoms. The gray-box models consider the involved structures in the symptoms appearance as well as the final disease symptoms. These models can effectively save time and be cost-effective for the researchers and help them select appropriate treatment mechanisms among all possible options. In this review paper, first, efforts are made to investigate some studies on PD quantitative analysis. Then, PD quantitative models will be reviewed. Finally, the results of using such models are presented to some extent. PMID- 26546076 TI - Epigenetic Effects of Cannabis Exposure. AB - The past decade has witnessed a number of societal and political changes that have raised critical questions about the long-term impact of marijuana (Cannabis sativa) that are especially important given the prevalence of its abuse and that potential long-term effects still largely lack scientific data. Disturbances of the epigenome have generally been hypothesized as the molecular machinery underlying the persistent, often tissue-specific transcriptional and behavioral effects of cannabinoids that have been observed within one's lifetime and even into the subsequent generation. Here, we provide an overview of the current published scientific literature that has examined epigenetic effects of cannabinoids. Though mechanistic insights about the epigenome remain sparse, accumulating data in humans and animal models have begun to reveal aberrant epigenetic modifications in brain and the periphery linked to cannabis exposure. Expansion of such knowledge and causal molecular relationships could help provide novel targets for future therapeutic interventions. PMID- 26546077 TI - Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool? AB - OBJECTIVE: To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low < 5%; intermediate >= 5% and < 7.5%; high >= 7.5%) taken from a prospective cohort "FRIDEX". METHODS: A retrospective study of 1090 women aged >= 40 and <= 90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed. RESULTS: When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group. CONCLUSIONS: Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients. PMID- 26546078 TI - Time Isn't of the Essence: Activating Goals Rather Than Imposing Delays Improves Inhibitory Control in Children. AB - Is it easier to inhibit inappropriate behaviors if one pauses before acting? An important finding for theory and intervention is that children's inhibitory control improves if an adult imposes a delay before they can act. Such findings have suggested that the passage of time allows impulsive urges to dissipate passively. However, in prior studies with imposed delays, children were also reminded about what they should be doing, which may have aided their activation of goal-relevant information. We tested this possibility by independently manipulating delays and task reminders, and measuring 3-year-olds' abilities to inhibit opening boxes in a go/no-go box-search task. Task reminders, but not adult-imposed delays, improved children's response inhibition. However, as in prior work, children who spontaneously delayed their action longer on go trials exhibited better response inhibition on no-go trials. These results pose a challenge to the view that the passage of time plays a causal role, suggest that spontaneous delays index other processes that improve inhibitory control, and highlight the importance of goal activation in developing inhibitory control. PMID- 26546079 TI - Put Your Imperfections Behind You: Temporal Landmarks Spur Goal Initiation When They Signal New Beginnings. AB - People often fail to muster the motivation needed to initiate goal pursuit. Across five laboratory experiments, we explored occasions when people naturally experience enhanced motivation to take actions that facilitate goal pursuit and why certain dates are more likely to spur goal initiation than others. We present causal evidence that emphasizing a temporal landmark denoting the beginning of a new time period increases people's intentions to initiate goal pursuit. In addition, we propose and show that people's strengthened motivation to begin pursuing their aspirations following such temporal landmarks originates in part from the psychological disassociation these landmarks induce from a person's past, imperfect self. PMID- 26546080 TI - The Effects of Social Context and Acute Stress on Decision Making Under Uncertainty. AB - Uncertainty preferences are typically studied in neutral, nonsocial contexts. This approach, however, fails to capture the dynamic factors that influence choices under uncertainty in the real world. Our goal was twofold: to test whether uncertainty valuation is similar across social and nonsocial contexts, and to investigate the effects of acute stress on uncertainty preferences. Subjects completed matched gambling and trust games following either a control or a stress manipulation. Those who were not under stress exhibited no differences between the amount of money gambled and the amount of money entrusted to partners. In comparison, stressed subjects gambled more money but entrusted less money to partners. We further found that irrespective of stress, subjects were highly attuned to irrelevant feedback in the nonsocial, gambling context, believing that every loss led to a greater chance of winning (the gamblers' fallacy). However, when deciding to trust a stranger, control subjects behaved rationally, treating each new interaction as independent. Stress compromised this adaptive behavior, increasing sensitivity to irrelevant social feedback. PMID- 26546081 TI - Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells. AB - Lung cancer is the most common type of malignant tumor, but the molecular mechanisms for lung cancer progression remains to be elusive. Here, we demonstrated that FBP1 (Fructose-1, 6-bisphosphatase) was frequently down regulated in lung cancer tissues and cells, and FBP1 down-regulation was associated with poor prognosis in lung cancer patients. Restored FBP1 expression inhibited glucose uptake and lactate production, but induced oxygen consumption. Restored FBP1 expression also inhibited lung cancer cells proliferation and invasion under hypoxia in vitro, and inhibited lung cancer growth in vivo. Moreover, we confirmed DNA methylation in the promoter contributed to the decrease of FBP1 expression in lung cancer cells. We identified Zinc finger E-box binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. Our findings indicate that the down-regulation of FBP1 is a critical oncogenic event in lung cancer progression. PMID- 26546082 TI - Seed trait-mediated selection by rodents affects mutualistic interactions and seedling recruitment of co-occurring tree species. AB - As mutualists, seed dispersers may significantly affect mutualistic interactions and seedling recruitment of sympatric plants that share similar seed dispersers, but studies are rare. Here, we compared seed dispersal fitness in two co occurring plant species (Armeniaca sibirica and Amygdalus davidiana) that inhabit warm temperate deciduous forest in northern China. We tested the hypothesis that seed trait-mediated selection by rodents may influence mutualistic interactions with rodents and then seedling establishment of co-occurring plant species. A. davidiana seeds are larger and harder (thick endocarps) than A. sibirica seeds, but they have similar levels of nutrients (crude fat, crude protein), caloric value and tannin. More A. sibirica seedlings are found in the field. Semi-natural enclosure tests indicated that the two seed species were both harvested by the same six rodent species, but that A. sibirica had mutualistic interactions (scatter hoarding) with four rodent species (Apodemus peninsulae, A. agrarius, Sciurotamias davidianus, Tamias sibiricus), and A. davidiana with only one (S. davidianus). Tagged seed dispersal experiments in the field indicated that more A. sibirica seeds were scatter-hoarded by rodents, and more A. sibirica seeds survived to the next spring and became seedlings. A. sibirica seeds derive more benefit from seed dispersal by rodents than A. davidiana seeds, particularly in years with limited seed dispersers, which well explained the higher seedling recruitment of A. sibirica compared with that of A. davidiana under natural conditions. Our results suggest that seed dispersers may play a significant role in seedling recruitment and indirect competition between co-occurring plant species. PMID- 26546083 TI - Conversion of tropical lowland forest reduces nutrient return through litterfall, and alters nutrient use efficiency and seasonality of net primary production. AB - Tropical landscapes are not only rapidly transformed by ongoing land-use change, but are additionally confronted by increasing seasonal climate variation. There is an increasing demand for studies analyzing the effects and feedbacks on ecosystem functioning of large-scale conversions of tropical natural forest into intensively managed cash crop agriculture. We analyzed the seasonality of aboveground litterfall, fine root litter production, and aboveground woody biomass production (ANPP(woody)) in natural lowland forests, rubber agroforests under natural tree cover ("jungle rubber"), rubber and oil palm monocultures along a forest-to-agriculture transformation gradient in Sumatra. We hypothesized that the temporal fluctuation of litter production increases with increasing land use intensity, while the associated nutrient fluxes and nutrient use efficiency (NUE) decrease. Indeed, the seasonal variation of aboveground litter production and ANPP(woody) increased from the natural forest to the plantations, while aboveground litterfall generally decreased. Nutrient return through aboveground litter was mostly highest in the natural forest; however, it was significantly lower only in rubber plantations. NUE of N, P and K was lowest in the oil palm plantations, with natural forest and the rubber systems showing comparably high values. Root litter production was generally lower than leaf litter production in all systems, while the root-to-leaf ratio of litter C flux increased along the land-use intensity gradient. Our results suggest that nutrient and C cycles are more directly affected by climate seasonality in species-poor agricultural systems than in species-rich forests, and therefore might be more susceptible to inter-annual climate fluctuation and climate change. PMID- 26546084 TI - Digging for answers: contributions of density- and frequency-dependent factors on ectoparasite burden in a social mammal. AB - Due to the density-dependent nature of parasite transmission parasites are generally assumed to constrain the evolution of sociality. However, evidence for a correlation between group size and parasite burden is equivocal, particularly for mammals. Host contact rates may be modified by mobility of the host and parasite as well as social barriers. In the current study, we used the common mole-rat (Cryptomys hottentotus hottentotus), a social subterranean rodent, as a model system to investigate the effect of host density and frequency of contact rates on ectoparasite burdens. To address these factors we used a study species that naturally varies in population densities and intergroup contact rates across its geographic range. We found that ectoparasite prevalence, abundance and species richness decreased with increasing host density at a regional scale. At the same time, measures of parasite burden increased with intergroup contact rates. Ectoparasite burdens decreased with colony size at the group level possibly as a result of increased grooming rates. Equating group size with population density might be too simplistic an approach when assessing parasite distributions in social mammals. Our data suggest that frequency-dependent mechanisms may play a much greater role at a population level than density dependent mechanisms in determining parasite distributions in social species. We suggest that future studies should explicitly consider behavioural mechanisms that may affect parasite distribution. PMID- 26546086 TI - Erratum to: Bedtime ingestion of hypertension medications reduces the risk of new onset type 2 diabetes: a randomised controlled trial. PMID- 26546085 TI - Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries. AB - AIMS/HYPOTHESIS: While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries. METHODS: Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n = 26,198), T1D Exchange (T1DX; n = 13,755) and the National Paediatric Diabetes Audit (NPDA; n = 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared. RESULTS: The overall mean HbA1c level was higher in the NPDA (8.9 +/- 1.6% [74 +/- 17.5 mmol/mol]) than in the DPV (8.0 +/- 1.6% [64 +/- 17.0 mmol/mol], p < 0.001) and T1DX (8.3 +/- 1.4% [68 +/- 15.4 mmol/mol], p < 0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%, p < 0.001) and T1DX (47%, p < 0.001). In a pooled analysis, pump use was associated with a lower mean HbA1c (pump: 8.0 +/- 1.2% [64 +/- 13.3 mmol/mol] vs injection: 8.5 +/- 1.7% [69 +/- 18.7 mmol/mol], p < 0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (p < 0.001) and boys were treated with a pump less often compared with girls (p < 0.001). CONCLUSIONS/INTERPRETATION: Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy. PMID- 26546087 TI - An Unusual Chimeric Diterpene Synthase from Emericella variecolor and Its Functional Conversion into a Sesterterpene Synthase by Domain Swapping. AB - Di- and sesterterpene synthases produce C20 and C25 isoprenoid scaffolds from geranylgeranyl pyrophosphate (GGPP) and geranylfarnesyl pyrophosphate (GFPP), respectively. By genome mining of the fungus Emericella variecolor, we identified a multitasking chimeric terpene synthase, EvVS, which has terpene cyclase (TC) and prenyltransferase (PT) domains. Heterologous gene expression in Aspergillus oryzae led to the isolation of variediene (1), a novel tricyclic diterpene hydrocarbon. Intriguingly, in vitro reaction with the enzyme afforded the new macrocyclic sesterterpene 2 as a minor product from dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). The TC domain thus produces the diterpene 1 and the sesterterpene 2 from GGPP and GFPP, respectively. Notably, a domain swap of the PT domain of EvVS with that of another chimeric sesterterpene synthase, EvSS, successfully resulted in the production of 2 in vivo as well. Cyclization mechanisms for the production of these two compounds are proposed. PMID- 26546088 TI - Biosynthesis of platform chemical 3-hydroxypropionic acid (3-HP) directly from CO2 in cyanobacterium Synechocystis sp. PCC 6803. AB - 3-hydroxypropionic acid (3-HP) is an important platform chemical with a wide range of applications. So far large-scale production of 3-HP has been mainly through petroleum-based chemical processes, whose sustainability and environmental issues have attracted widespread attention. With the ability to fix CO2 directly, cyanobacteria have been engineered as an autotrophic microbial cell factory to produce fuels and chemicals. In this study, we constructed the biosynthetic pathway of 3-HP in cyanobacterium Synechocystis sp. PCC 6803, and then optimized the system through the following approaches: i) increasing expression of malonyl-CoA reductase (MCR) gene using different promoters and cultivation conditions; ii) enhancing supply of the precursor malonyl-CoA by overexpressing acetyl-CoA carboxylase and biotinilase; iii) improving NADPH supply by overexpressing the NAD(P) transhydrogenase gene; iv) directing more carbon flux into 3-HP by inactivating the competing pathways of PHA and acetate biosynthesis. Together, the efforts led to a production of 837.18 mg L(-1) (348.8 mg/g dry cell weight) 3-HP directly from CO2 in Synechocystis after 6 days cultivation, demonstrating the feasibility photosynthetic production of 3-HP directly from sunlight and CO2 in cyanobacteria. In addition, the results showed that overexpression of the ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) gene from Anabaena sp. PCC 7120 and Synechococcus sp. PCC 7942 led to no increase of 3-HP production, suggesting CO2 fixation may not be a rate limiting step for 3-HP biosynthesis in Synechocystis. PMID- 26546089 TI - A highly efficient single-step, markerless strategy for multi-copy chromosomal integration of large biochemical pathways in Saccharomyces cerevisiae. AB - Despite recent advances in genome editing capabilities for the model organism Saccharomyces cerevisiae, the chromosomal integration of large biochemical pathways for stable industrial production remains challenging. In this work, we developed a simple platform for high-efficiency, single-step, markerless, multi copy chromosomal integration of full biochemical pathways in Saccharomyces cerevisiae. In this Di-CRISPR (delta integration CRISPR-Cas) platform based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated systems (Cas), we specifically designed guide RNA sequences to target multiple delta sites in the yeast genome. The generation of double stranded breaks at the delta sites allowed simultaneous integration of multiple copies of linearized donor DNA containing large biochemical pathways. With our newly developed Di-CRISPR platform, we were able to attain highly efficient and markerless integration of large biochemical pathways and achieve an unprecedented 18-copy genomic integration of a 24 kb combined xylose utilization and (R,R)-2,3 butanediol (BDO) production pathway in a single step, thus generating a strain that was able to produce BDO directly from xylose. The simplicity and high efficiency of the Di-CRISPR platform could provide a superior alternative to high copy plasmids and would render this platform an invaluable tool for genome editing and metabolic engineering in S. cerevisiae. PMID- 26546090 TI - Comparative profiling of extractable proteins in extracellular matrices of porcine cholecyst and jejunum intended for preparation of tissue engineering scaffolds. AB - Scaffolds prepared from cholecyst and jejunum have differential immunological potential, despite similar biocompatibility, when used as subcutaneous grafts. The reason for differential immunogenicity is probably due to differences in the nature of protein composition and biomolecules in the extracellular matrices (ECMs) of source organs that are used for preparation of the scaffolds. Against this background, the present study aims to identify the extractable proteins of ECMs derived from porcine cholecyst and jejunum. The proteins were extracted and identified through a conventional database search following sodium dodecyl sulfate-polyacrylamide gel-electrophoresis separation and mass spectroscopy. The resultant protein profile was analyzed and at least 154 proteins in cholecyst derived extracellular matrix (CDE) and 186 proteins in jejunum-derived extracellular matrix (JDE) were identified. Both the matrices contained several extracelluar proteins including fibronectin, nidogen, decorin, and lumican that are known to participate in wound healing responses. However, the CDE had fewer cellular proteins than JDE, especially the latter contained class-I and class-II histocompatibility antigens which are incriminated as potent immunogens responsible for graft rejection. The results of the study suggested that the ECMs used for the scaffold preparation need not be "acellular" and differences in the protein composition of the ECMs might have caused the differential wound healing responses. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 489-496, 2017. PMID- 26546091 TI - Towards Improved Care of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope Patients: A Call to Action in Australia. PMID- 26546092 TI - Giant Coronary Ostial Aneurysms after Aortic Root Replacement. PMID- 26546093 TI - Extralobar Pulmonary Sequestration Presenting with Recurring Massive Pleural Effusion in a Young Woman: A Challenging Case. AB - We report a case of extralobar pulmonary sequestration (ELS) in a young woman, presenting with right recurring massive pleural effusion. The patient initially underwent a diagnostic Video Assisted Thoracic Surgery (VATS) for a suspected diffuse malignancy. After the aspiration of the pleural effusion we observed a highly vascularised cystic mass, with its origin from the right lower lobe. As we tried to retract the right lower lobe, the mass broke with massive bleeding requiring emergency right lateral thoracotomy. The mass was succesfully excised, resembling an extra-lobar pulmonary sequestration. The patient was discharged on post-operative day 5. PMID- 26546094 TI - Dopamine Administration is a Risk Factor for Delirium in Patients Undergoing Coronary Artery Bypass Surgery. AB - BACKGROUND: Delirium is an important morbidity following heart surgery. We sought to determine whether dopamine infusion is associated with increased risk of delirium in patients undergoing coronary artery bypass grafting. METHODS: A total of 137 patients (mean age; 61.02+/-7.83, 105 males) were included in the study. Patients undergoing isolated coronary artery bypass grafting were considered eligible and those with preoperative neurological deficit or significant neurocognitive disorders, dementia or psychiatric disorders were excluded. Primary outcome measure was occurrence of delirium within 72 hours after operation. The diagnosis of delirium was made using confusion assessment method for the intensive care unit questionnaire. Both administration of dopamine as a dichotomised variable and the total amount of dopamine per kg body-weight were included in two different logistic regression models. RESULTS: Delirium occurred in 18 (13.1%) patients. Age adjusted Mantel-Haenszel relative risk for delirium with receiving dopamine was 4.62. Relative risk was 2.37 (0.18 to 31.28, 95% CI, p=0.51) in total doses over 10mg whereas it was 3.55 (1.16 to 10.89 95% CI, p=0.02) in total doses over 30 mg per kg body-weight. Older age (p=0.03), dopamine administration (OR: 9.227 95% CI, 2.688-32.022, p<0.001) and the amount of dopamine administered (OR: 1.072, 95% CI, 1.032-1.115, p<0.001) were independent predictors for delirium 72 hours after surgery. CONCLUSION: Along with older age, dopamine infusion--even in low doses but more probably in higher doses--emerged as an independent risk factor for delirium in patients undergoing CABG. Further study is needed to confirm the validity of results presented. PMID- 26546095 TI - High Arrhythmic Burden but Low Mortality during Long-term Follow-up in Arrhythmogenic Right Ventricular Cardiomyopathy. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high incidence of ventricular tachyarrhythmia and sudden death. The mainstay of management is the implantable cardioverter defibrillator (ICD). A small number of patient cohorts have generated a large number of reports. METHODS: Prospective registry data supplemented with clinical and ICD records of 30 patients with ARVC fulfilling the 2010 modified Task Force Criteria. This cohort has not been reported on previously. RESULTS: Median age at diagnosis: 46yrs (range 21-68); 20 (80%) male; six (19%) Maori. Duration of follow-up: 7.4yrs (range 1.7-23). Implantable cardioverter defibrillator implantation in 26; three (12%) for resuscitated sudden cardiac death; 17 (65%) for symptomatic ventricular tachyarrhythmia; three (12%) for syncope; and three (12%) for family history of sudden death attributable to ARVC. Two patients died during follow-up, one had an ICD, though died of a carcinoma. Thirteen (50%) experienced appropriate ICD therapy with median time to therapy 12 months, and four (15%) experienced inappropriate shock therapy. Male gender was an independent predictor of appropriate ICD therapy (HR 1.6, 95% CI 1.5-2.7, P=0.01). CONCLUSIONS: The long-term prognosis of patients with ARVC is favourable although high proportions receive appropriate ICD therapy. Male gender is an independent predictor of appropriate ICD therapy. PMID- 26546096 TI - Long-term Outcomes of Thoracoscopic Anatomic Resections and Systematic Lymphadenectomy for Elderly High-risk Patients with Stage IB Non-small-cell Lung Cancer. AB - BACKGROUND: To evaluate the efficacy and long-term survival outcomes of complete video-assisted thoracoscopic surgery (C-VATS) for the resection of anatomic pulmonary segments and systematic lymphadenectomy in the treatment of elderly and high-risk patients with stage IB for non-small cell lung cancer (NSCLC). METHODS: 242 elderly patients (>=65 years), who were operated on by the same operational team, were divided into high-risk group and conventional risk group from August 2008 to December 2010. All patients were diagnosed in stage IB (pT status: >2 to <=3) NSCLC by biopsy and examination of PET-CT before operation. The high-risk patients were identified with severe cardiopulmonary and other system dysfunctions as follow-up criteria. They were treated with VATS anatomic pulmonary segments and systematic lymphadenectomy. The conventional risk patients with adequate cardiopulmonary reserve were treated with VATS radical lobectomy and systematic lymphadenectomy. The clinical and pathological data were recorded. The total survival, tumour-free survival, recurrence time and character of patients were followed-up. Appropriate statistical analyses involved the chi(2) test and Kaplan-Meier estimates of total survival and tumour-free survival. RESULTS: A total of 242 patients underwent surgical resection during our study period: Anatomic pulmonary segments in 116 patients and lobectomy in 126. The operative time and blood loss of the VATS anatomic pulmonary segments group (78.0+/-35.0 min, 95.6+/-30.4 ml) were significantly less than those of the VATS radical resection group (108.0+/-25.0 min, 165.6+/-58.4 ml). Neither group experienced post-operative death. The overall and tumour-free survival rate of the VATS anatomic pulmonary segments group within five years were 62.07% and 29.31%, and those of the VATS radical resection group were 63.49% and 33.33%,%; there was no significant difference (P>0.5). The recurrence rates of the VATS anatomic pulmonary segment group and VATS radical resection group were 13.79% and 12.70%; there was no significant difference (P>0.5). CONCLUSIONS: Thorascopic segmentectomy under anaesthesia and systematic lymphadenectomy is safe and minimally invasive and effective to treat a selected group of patients with stage IB NSCLC. PMID- 26546097 TI - Gender differences in caregiver-child relationship mediation of the association between violence exposure severity and adolescent behavior problems. AB - The main objectives of this study were to investigate (1) the relationship between mild, moderate, and severe violence exposure in the home and behavior problems in adolescents; (2) the caregiver-child relationship as a potential mediator in this relationship; and (3) gender differences. A series of path analyses were conducted using a sample drawn from the National Survey of Child and Adolescent Well-Being (NCSAW-I) of 848 adolescents (ages 11-15) who had been reported to Child Protective Services for maltreatment and who remained in their homes. Exposure to violence and the caregiver-child relationship were reported by adolescents. Both caregiver ratings and adolescent self-reports were used to assess adolescents' behavior problems. Path analysis indicated that exposure to mild and severe violence was directly associated with higher levels of child reported behavior problems. However, exposure to violence was not directly associated with caregiver ratings of adolescent behavior problems. The caregiver child relationship mediated the relationship between mild and moderate violence on both caregiver and child-reported adolescent behavior problems. Gender differences also emerged; for girls, the caregiver-child relationship mediated the effects of mild and moderate violence, whereas for boys, it mediated the effects of severe violence on behavior problems. Study findings suggest caregiver child relationships as a critical underlying mechanism in the association between violence exposure and adolescent behavior problems, highlighting the importance of adding the caregiver-child relationship factor to intervention efforts. PMID- 26546099 TI - A disturbance observer-based adaptive control approach for flexure beam nano manipulators. AB - This paper presents a systematic modeling and control methodology for a two dimensional flexure beam-based servo stage supporting micro/nano manipulations. Compared with conventional mechatronic systems, such systems have major control challenges including cross-axis coupling, dynamical uncertainties, as well as input saturations, which may have adverse effects on system performance unless effectively eliminated. A novel disturbance observer-based adaptive backstepping like control approach is developed for high precision servo manipulation purposes, which effectively accommodates model uncertainties and coupling dynamics. An auxiliary system is also introduced, on top of the proposed control scheme, to compensate the input saturations. The proposed control architecture is deployed on a customized-designed nano manipulating system featured with a flexure beam structure and voice coil actuators (VCA). Real time experiments on various manipulating tasks, such as trajectory/contour tracking, demonstrate precision errors of less than 1%. PMID- 26546098 TI - Comparing Vocal Fold Contact Criteria Derived From Audio and Electroglottographic Signals. AB - OBJECTIVES: Collision threshold pressure (CTP), that is, the lowest subglottal pressure facilitating vocal fold contact during phonation, is likely to reflect relevant vocal fold properties. The amplitude of an electroglottographic (EGG) signal or the amplitude of its first derivative (dEGG) has been used as criterion of such contact. Manual measurement of CTP is time consuming, making the development of a simpler, alternative method desirable. METHOD: In this investigation, we compare CTP values measured manually to values automatically derived from dEGG and to values derived from a set of alternative parameters, some obtained from audio and some from EGG signals. One of the parameters was the novel EGG wavegram, which visualizes sequences of EGG or dEGG cycles, normalized with respect to period and amplitude. Raters with and without previous acquaintance with EGG analysis marked the disappearance of vocal fold contact in dEGG and in wavegram displays of /pa:/-sequences produced with continuously decreasing vocal loudness by seven singer subjects. RESULTS: Vocal fold contact was mostly identified accurately in displays of both dEGG amplitude and wavegram. Automatically derived CTP values showed high correlation with those measured manually and with those derived from the ratings of the visual displays. Seven other parameters were tested as criteria of such contact. Mainly, because of noise in the EGG signal, most of them yielded CTP values differing considerably from those derived from the manual and the automatic methods, although the EGG spectrum slope showed a high correlation. CONCLUSION: The possibility of measuring CTP automatically seems promising for future investigations. PMID- 26546100 TI - Use of internal consistency coefficients for estimating reliability of experimental task scores. AB - Reliabilities of scores for experimental tasks are likely to differ from one study to another to the extent that the task stimuli change, the number of trials varies, the type of individuals taking the task changes, the administration conditions are altered, or the focal task variable differs. Given that reliabilities vary as a function of the design of these tasks and the characteristics of the individuals taking them, making inferences about the reliability of scores in an ongoing study based on reliability estimates from prior studies is precarious. Thus, it would be advantageous to estimate reliability based on data from the ongoing study. We argue that internal consistency estimates of reliability are underutilized for experimental task data and in many applications could provide this information using a single administration of a task. We discuss different methods for computing internal consistency estimates with a generalized coefficient alpha and the conditions under which these estimates are accurate. We illustrate use of these coefficients using data for three different tasks. PMID- 26546101 TI - Cyclization of Pyrene Oligomers: Cyclohexa-1,3-pyrenylene. AB - First synthesis of the macrocycle cyclohexa(1,3-pyrenylene) is achieved in six steps starting with pyrene, leading to a non-aggregating highly twisted blue light-emitting material. The cyclodehydrogenation of the macrocycle offers a promising synthesis route to holey-nanographene. PMID- 26546102 TI - Glutathione--linking cell proliferation to oxidative stress. AB - SIGNIFICANCE: The multifaceted functions of reduced glutathione (gamma-glutamyl cysteinyl-glycine; GSH) continue to fascinate plants and animal scientists, not least because of the dynamic relationships between GSH and reactive oxygen species (ROS) that underpin reduction/oxidation (redox) regulation and signalling. Here we consider the respective roles of ROS and GSH in the regulation of plant growth, with a particular focus on regulation of the plant cell cycle. Glutathione is discussed not only as a crucial low molecular weight redox buffer that shields nuclear processes against oxidative challenge but also a flexible regulator of genetic and epigenetic functions. RECENT ADVANCES: The intracellular compartmentalization of GSH during the cell cycle is remarkably consistent in plants and animals. Moreover, measurements of in vivo glutathione redox potentials reveal that the cellular environment is much more reducing than predicted from GSH/GSSG ratios measured in tissue extracts. The redox potential of the cytosol and nuclei of non-dividing plant cells is about -300 mV. This relatively low redox potential maintained even in cells experiencing oxidative stress by a number of mechanisms including vacuolar sequestration of GSSG. We propose that regulated ROS production linked to glutathione-mediated signalling events are the hallmark of viable cells within a changing and challenging environment. CRITICAL ISSUES: The concept that the cell cycle in animals is subject to redox controls is well established but little is known about how ROS and GSH regulate this process in plants. However, it is increasingly likely that redox controls exist in plants, although possibly through different pathways. Moreover, redox-regulated proteins that function in cell cycle checkpoints remain to be identified in plants. While GSH-responsive genes have now been identified, the mechanisms that mediate and regulate protein glutathionylation in plants remain poorly defined. FUTURE DIRECTIONS: The nuclear GSH pool provides an appropriate redox environment for essential nuclear functions. Future work will focus on how this essential thiol interacts with the nuclear thioredoxin system and nitric oxide to regulate genetic and epigenetic mechanisms. The characterization of redox-regulated cell cycle proteins in plants, and the elucidation of mechanisms that facilitate GSH accumulation in the nucleus are keep steps to unravelling the complexities of nuclear redox controls. PMID- 26546104 TI - Pacemaker implantation after catheter ablation for atrial fibrillation. AB - BACKGROUND: Sinus node dysfunction requiring pacemaker implantation is commonly associated with atrial fibrillation (AF), but may not be clinically apparent until restoration of sinus rhythm with ablation or cardioversion. We sought to determine frequency, time course, and predictors for pacemaker implantation after catheter ablation, and to compare the overall rates to a matched cardioversion cohort. METHODS AND RESULTS: We conducted a retrospective analysis using a large US commercial insurance database and identified 12,158 AF patients who underwent catheter ablation between January 1, 2005 and December 31, 2012. Over an average of 2.4 years of follow-up, 5.6 % of the patients underwent pacemaker implantation. Using the Cox proportional hazards models, we found that risk of risks of pacemaker implantation was associated with older age (50-64 and >=65 versus <50 years), female gender, higher CHADS2 score (>=2 and 1 versus 0), higher Charlson index (>=2 versus 0-1), certain baseline comorbidities (conduction disorder, coronary atherosclerosis, and congestive heart failure), and the year of ablation. There was no significant difference in the risk of pacemaker implantation between ablation patients and propensity score (PS) matched cardioversion groups (3.5 versus. 4.1 % at 1 year and 8.8 versus 8.3 % at 5 years). CONCLUSION: Overall, pacemaker implantation occurs in about 1/28 patients within 1 year of catheter ablation. The overall implantation rate decreased between 2005 and 2012. Furthermore, the risk after ablation is similar to cardioversion, suggesting that patients require pacing due to a common underlying electrophysiologic substrate, rather than the ablation itself. PMID- 26546103 TI - Acupuncture ameliorates cognitive impairment and hippocampus neuronal loss in experimental vascular dementia through Nrf2-mediated antioxidant response. AB - Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation. PMID- 26546105 TI - Myocardial injury during radiofrequency and cryoablation of typical atrial flutter. AB - PURPOSE: Cardiac enzyme elevation after radiofrequency (RF) catheter ablation of atrial flutter (AFL) is common. Some studies found that cryoablation (CRYO) of AFL, compared to RF, is associated with higher levels of troponin, a finding that may indicate CRYO causes a greater amount of myocardial injury than RF. However, other investigations found no significant differences between troponin levels after CRYO versus RF. We have in a randomized study compared the post-procedural troponin I levels in RF and CRYO and the possible relation to procedural outcome and complications. METHODS: We randomized 153 patients with cavotricuspid isthmus (CTI)-dependent AFL to CRYO or RF (78 CRYO; 75 RF). RF was performed with a 3.5 mm open-irrigated-tip catheter, and CRYO was performed with an 8-mm-tip catheter. Troponin I levels were measured before and 6 h after ablation. RESULTS: Acute procedural success was achieved in 71/75 patients in the RF and in 72/78 patients in the CRYO. Troponin I levels were significantly elevated in both groups (baseline 0.012, 6th hour 0.35 ng/ml; p < 0.001). Troponin I levels were similar for RF and CRYO. Troponin I levels were higher in patients with acute failure compared to patients with acute success (0.48 +/- 0.4 and 0.34 +/- 0.16 ng/ml, p = 0.029); however, there was no difference between patients with or without late recurrence. There were no major complications in any group. CONCLUSION: RF and CRYO for CTI-dependent AFL resulted in similar amounts of procedural myocardial injury. Troponin I levels had no prognostic value for late recurrence of AFL and there were no complications related to high troponin I levels. PMID- 26546106 TI - Characteristics of Exceptional or Super Responders to Cancer Drugs. AB - OBJECTIVE: To summarize case reports of exceptional and super responders already published in the biomedical literature. PATIENTS AND METHODS: We searched for published case reports or abstracts of exceptional or super responders to a cancer drug using PubMed and Google Scholar search engines. Pooling such reports is widely considered a promising research strategy and the subject of several ongoing investigations, including the National Cancer Institute's Exceptional Responders Initiative. All articles were read in full, including relevant references. We extracted clinical characteristics of exceptional or super responders, including age, tumor type, drug, genetic mutations, depth of response, duration of response, number of previous lines of therapy, duration of response to a previous line of therapy, and the number of patients treated similarly to identify the exceptional case. This study was performed between March 1, 2015, and April 30, 2015. RESULTS: Among 489 articles, 32 exceptional responders were identified. The most common malignancies described were renal cell cancer (5 of 32 [16%]) and urothelial carcinoma (4 of 32 [13%]). The use of targeted agents was common in these cases (26 of 32 [81%]), particularly inhibitors of the mTOR pathway (16 of 32 [50%]). The median duration of response among responders was 17.5 months, and 59% (19 of 32) of the patients were last known to be alive with continuing response or stable disease. Notably, 46% (12 of 26) of the patients had received 2 or more previous lines of therapy and 6 of the 32 cases (19%) did not report this information. Few authors report the number of patients treated similarly to observe the super response (12 of 32 [38%]). CONCLUSION: Exceptional or super responders to cancer drugs have been described in the literature; however, there is incompleteness in the reporting of relevant data that may help clarify whether such responses are secondary to treatment or reflect underlying biology. PMID- 26546107 TI - Primary Myelodysplastic Syndromes: The Mayo Clinic Experience With 1000 Patients. AB - OBJECTIVES: To share our 25 years of experience with patients with primary myelodysplastic syndromes (MDS) and to describe the natural history of the disease including presenting clinical and laboratory characteristics and long term disease outcomes. PATIENTS AND METHODS: One thousand consecutive patients with primary MDS evaluated at Mayo Clinic between January 1, 1989, and May 1, 2014, were considered. The Revised International Prognostic Scoring System and other risk models were applied for risk stratification. Separate analyses were conducted for patients diagnosed before 2005 (n=531) and after 2005 (n=469). RESULTS: Eighty-five percent of patients were older than 60 years (median age, 72 years), with 69% being men. The median follow-up period was 27 months (range, 0 300 months), during which time 808 (81%) deaths and 129 (13%) leukemic transformations were documented. Median survival and leukemic transformation rates were similar in patients diagnosed before or after 2005, despite the significantly higher use of hypomethylating agents in the latter group: 33 months vs 28 months (P=.46) and 13% vs 10% (P=.92), respectively. Revised International Prognostic Scoring System risk distribution was similar in patients diagnosed before or after 2005 (P=.23): 17% were categorized as very low, 36% low, 21% intermediate, 15% high, and 11% very high risk, with a median survival of 72, 43, 24, 18, and 7 months, respectively (P<.001). We found Revised International Prognostic Scoring System cytogenetic risk categorization to be suboptimal in its performance, whereas contemporary prognostic models were broadly similar in their performance. CONCLUSION: The poor outcome in patients with MDS does not appear to have improved over time. Current risk stratification systems for MDS are not substantially different from each other. There is a dire need for drugs that are truly disease modifying and risk models that incorporate prognostically relevant mutations. PMID- 26546108 TI - Burden of type 2 diabetes in Mexico: past, current and future prevalence and incidence rates. AB - INTRODUCTION: Mexico diabetes prevalence has increased dramatically in recent years. However, no national incidence estimates exist, hampering the assessment of diabetes trends and precluding the development of burden of disease analyses to inform public health policy decision-making. Here we provide evidence regarding current magnitude of diabetes in Mexico and its future trends. METHODS: We used data from the Mexico National Health and Nutrition Survey, and age-period cohort models to estimate prevalence and incidence of self-reported diagnosed diabetes by age, sex, calendar-year (1960-2012), and birth-cohort (1920-1980). We project future rates under three alternative incidence scenarios using demographic projections of the Mexican population from 2010-2050 and a Multi cohort Diabetes Markov Model. RESULTS: Adult (ages 20+) diagnosed diabetes prevalence in Mexico increased from 7% to 8.9% from 2006 to 2012. Diabetes prevalence increases with age, peaking around ages 65-68 to then decrease. Age specific incidence follows similar patterns, but peaks around ages 57-59. We estimate that diagnosed diabetes incidence increased exponentially during 1960 2012, roughly doubling every 10 years. Projected rates under three age-specific incidence scenarios suggest diabetes prevalence among adults (ages 20+) may reach 13.7-22.5% by 2050, affecting 15-25 million individuals, with a lifetime risk of 1 in 3 to 1 in 2. CONCLUSIONS: Diabetes prevalence in Mexico will continue to increase even if current incidence rates remain unchanged. Continued implementation of policies to reduce obesity rates, increase physical activity, and improve population diet, in tandem with diabetes surveillance and other risk control measures is paramount to substantially reduce the burden of diabetes in Mexico. PMID- 26546109 TI - Overexpression of Aiolos in Peripheral Blood Mononuclear Cell Subsets from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis. AB - Genetic studies demonstrate that the Aiolos polymorphisms contribute to the susceptibility to autoimmune diseases. The purpose of the study was to investigate the Aiolos expression in lymphocytes and monocytes in the peripheral blood from patients with SLE and RA, and to explore the correlation between Aiolos expression in cell subsets and laboratory measurements. Peripheral blood mononuclear cells (PBMC) from 32 patients with SLE, 35 patients with RA, and 37 healthy controls were purified. Aiolos expression in PBMC subsets was examined by flow cytometry. In SLE patients, a much higher percentage of Aiolos + CD8+ T cells and Aiolos + CD14+ monocytes was found, when compared with healthy controls (p = 8.29 * 10(-5) and p = 1.01 * 10(-5), respectively). Furthermore, the percentage of CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes expressing Aiolos in RA patients was also determined and each found higher than that in healthy controls (p = 0.009, p = 4.11 * 10(-5), p = 0.001, and p = 1.11 * 10(-5), respectively). The percentage of Aiolos + CD8+ T cells was weakly correlated with ESR in SLE patients and RF in RA patients (r s = 0.37, p = 0.038; r s = 0.34, p = 0.044, respectively). On the other hand, the percentage of Aiolos + CD14+ monocytes was significantly correlated with multiple laboratory measurements, including ESR, creatinine, CRP, LDH, proteinuria, albumin, and ACCPA in patients (r s = 0.62, p < 0.001; r s = 0.65, p < 0.001; r s = 0.44, p = 0.010; r s = 0.42, p = 0.022; r s = 0.52, p = 0.013; r s = 0.34, p = 0.048, respectively). To our knowledge, it is the first study to demonstrate overexpression of Aiolos in PBMC subsets in SLE and RA patients. The results indicate that overexpression of Aiolos may contribute to pathogenesis of SLE and RA. PMID- 26546110 TI - Second toe microsurgical free-flap for aesthetic and sensory reconstruction of palmar soft tissue defects of fingers. AB - OBJECTIVES: To illustrate the surgical methods and clinical efficacy of microsurgical free-flaps obtained from second toe for the reconstruction of palmar soft-tissue defect of fingers. METHODS: We enrolled 22 patients (13 men and 9 women), who received second toe free-flap for 22 finger defects between August 2007 and July 2013. The average age was 35 years (range, 18-62 years). The average size of flap was 2.7 cm * 2.0 cm (range, 1.5 cm * 1.5 cm-3.5 cm * 2.5 cm). RESULTS: All flaps survived well without any complications. Follow-up period ranged from 8 to 30 months (mean 15 months). The Visual Analog Scale for flap appearance (VAS flap) was ranged from 8 to 10 (average, 9.5). Based on the CISS questionnaires, 6 cases had mild cold intolerance. The average value of Michigan Hand Outcome Questionnaire (MHOQ) scoring for overall hand function was 8 (range, 5-13). The sensibility outcomes in 10 patients who underwent nerve repair were satisfactory. Average value of static two point discrimination (2PD) was 6.4 mm (range, 4-10 mm) and SWM test was 3.45 (range 2.83-4.12). CONCLUSIONS: Second toe free micro-flap is a very useful and reliable alternative for the reconstruction of palmer soft-tissue defect of fingers. LEVEL OF EVIDENCE: IV. PMID- 26546111 TI - Has the Angelina Jolie effect led to an increase in risk reducing mastectomy and breast reconstruction in Wales: A retrospective, single centre cohort study. PMID- 26546112 TI - Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action. AB - Adipose tissue is a rich source of cells with emerging promise for tissue engineering and regenerative medicine. The stromal vascular fraction (SVF), in particular, is an eclectic composite of cells with progenitor activity that includes preadipocytes, mesenchymal stem cells, pericytes, endothelial cells, and macrophages. SVF has enormous potential for therapeutic application and is being investigated for multiple clinical indications including lipotransfer, diabetes related complications, nerve regeneration, burn wounds and numerous others. In Part 2 of our review, we explore the basic science behind the regenerative success of the SVF and discuss significant mechanisms that are at play. The existing literature suggests that angiogenesis, immunomodulation, differentiation, and extracellular matrix secretion are the main avenues through which regeneration and healing is achieved by the stromal vascular fraction. PMID- 26546113 TI - Kawasaki Disease in a 2-year-old Child with Dengue Fever. PMID- 26546114 TI - Ptbp1 and Exosc9 knockdowns trigger skin stability defects through different pathways. AB - In humans, genetic diseases affecting skin integrity (genodermatoses) are generally caused by mutations in a small number of genes that encode structural components of the dermal-epidermal junctions. In this article, we first show that inactivation of both exosc9, which encodes a component of the RNA exosome, and ptbp1, which encodes an RNA-binding protein abundant in Xenopus embryonic skin, impairs embryonic Xenopus skin development, with the appearance of dorsal blisters along the anterior part of the fin. However, histological and electron microscopy analyses revealed that the two phenotypes are distinct. Exosc9 morphants are characterized by an increase in the apical surface of the goblet cells, loss of adhesion between the sensorial and peridermal layers, and a decrease in the number of ciliated cells within the blisters. Ptbp1 morphants are characterized by an altered goblet cell morphology. Gene expression profiling by deep RNA sequencing showed that the expression of epidermal and genodermatosis related genes is also differentially affected in the two morphants, indicating that alterations in post-transcriptional regulations can lead to skin developmental defects through different routes. Therefore, the developing larval epidermis of Xenopus will prove to be a useful model for dissecting the post transcriptional regulatory network involved in skin development and stability with significant implications for human diseases. PMID- 26546115 TI - QCM-D study of nanoparticle interactions. AB - Quartz crystal microbalance with dissipation monitoring (QCM-D) has been proven to be a powerful research tool to investigate in situ interactions between nanoparticles and different functionalized surfaces in liquids. QCM-D can also be used to quantitatively determine adsorption kinetics of polymers, DNA and proteins from solutions on various substrate surfaces while providing insights into conformations of adsorbed molecules. This review aims to provide a comprehensive overview on various important applications of QCM-D, focusing on deposition of nanoparticles and attachment-detachment of nanoparticles on model membranes in complex fluid systems. We will first describe the working principle of QCM-D and DLVO theory pertinent to understanding nanoparticle deposition phenomena. The interactions between different nanoparticles and functionalized surfaces for different application areas are then critically reviewed. Finally, the potential applications of QCM-D in other important fields are proposed and knowledge gaps are identified. PMID- 26546116 TI - An intronic RNA structure modulates expression of the mRNA biogenesis factor Sus1. AB - Sus1 is a conserved protein involved in chromatin remodeling and mRNA biogenesis. Unlike most yeast genes, the SUS1 pre-mRNA of Saccharomyces cerevisiae contains two introns and is alternatively spliced, retaining one or both introns in response to changes in environmental conditions. SUS1 splicing may allow the cell to control Sus1 expression, but the mechanisms that regulate this process remain unknown. Using in silico analyses together with NMR spectroscopy, gel electrophoresis, and UV thermal denaturation experiments, we show that the downstream intron (I2) of SUS1 forms a weakly stable, 37-nucleotide stem-loop structure containing the branch site near its apical loop and the 3' splice site after the stem terminus. A cellular assay revealed that two of four mutants containing altered I2 structures had significantly impaired SUS1 expression. Semiquantitative RT-PCR experiments indicated that all mutants accumulated unspliced SUS1 pre-mRNA and/or induced distorted levels of fully spliced mRNA relative to wild type. Concomitantly, Sus1 cellular functions in histone H2B deubiquitination and mRNA export were affected in I2 hairpin mutants that inhibited splicing. This work demonstrates that I2 structure is relevant for SUS1 expression, and that this effect is likely exerted through modulation of splicing. PMID- 26546117 TI - Breast Cancer and Menopausal Hormone Therapy by Race/Ethnicity and Body Mass Index. AB - In analyses combining estrogen with or without progestin, some observational studies describe minimal breast cancer risk in obese and black women. Therefore, we examined these suggested interactions in the two Women's Health Initiative (WHI) randomized hormone therapy trials. The estrogen plus progestin trial entered 16 608 postmenopausal women with a uterus, while the estrogen trial entered 10 736 postmenopausal women with prior hysterectomy. Hazard ratios (HRs), 95% confidence intervals (CIs), and P values from log-rank x(2) statistics were estimated from Cox proportional hazards models with subgroup analyses based on tests of interaction. All statistical tests were two-sided. Estrogen plus progestin statistically significantly increased breast cancer incidence (HR = 1.28, 95% CI = 1.11 to 1.48, P < .001), with hazard ratios greater than 1 in all body mass index (BMI) subgroups (P interaction = .58) and hazard ratios greater than 1 in black and white women (P interaction = .96). In contrast, estrogen alone statistically significantly decreased breast cancer incidence (HR = 0.79, 95% CI = 0.65 to 0.90, P = .02), with hazard ratios lower than 1 in all BMI subgroups (P interaction = .86) and hazard ratios lower than 1 in black and white women, where analyses with limited numbers suggest somewhat greater reduction in black women (P interaction = .09). In summary, estrogen plus progestin and estrogen alone have opposite effects on breast cancer incidence, with no statistically significant interactions by race/ethnicity or BMI. Therefore, observational studies should not combine these two regimens when examining breast cancer risk. PMID- 26546118 TI - Peculiar and rapid photocatalytic degradation of tetrabromodiphenyl ethers over Ag/TiO2 induced by interaction between silver nanoparticles and bromine atoms in the target. AB - As a typical moderately-brominated diphenylethers, 2,2',4,4'-tetrabromodiphenyl ether (BDE47) is hardly debrominated by a conventional TiO2-mediated photocatalysis. However, its reductive debromination was rapid achieved over silver nanoparticle-loaded TiO2 (Ag/TiO2) in UV-irradiated anoxic acetonitrile water within 13 min. An "Ag-promoted electron transfer and C-Br cleavage" concept was proposed based on experimental results and density functional theory calculations. Ag(0) exerted affinity interaction with bromine atoms, and the storing of electrons on Ag(0) increased the binding interaction, which elongated the C-Br bond of BDE47 and facilitated its cleavage. The initiating of the BDE47 debromination on Ag(0) required an induction period to enrich a critical amount of electrons, leading to a stronger driving force for both injecting electron to BDE47 and stretching the C-Br bond. Stronger photo-excitation, higher polar solvent, and a moderate Ag(0) load strengthened the interfacial electron transfer over Ag/TiO2, and thereby shortening the induction time and accelerating the BDE47 degradation. PMID- 26546119 TI - Watch and Wait?--Elevated Pretreatment CEA Is Associated with Decreased Pathological Complete Response in Rectal Cancer. AB - INTRODUCTION: Between 10 and 30% of rectal cancer patients experience pathological complete response after neoadjuvant treatment. However, physiological factors predicting which patients will experience tumor response are largely unknown. Previous single-institution studies have suggested an association between elevated pretreatment carcinoembryonic antigen and decreased pathological complete response. METHODS: Clinical stage II-III rectal cancer patients undergoing neoadjuvant chemoradiotherapy and surgical resection were selected from the 2006-2011 National Cancer Data Base. Multivariable analysis was used to examine the association between elevated pretreatment carcinoembryonic antigen and pathological complete response, pathological tumor regression, tumor downstaging, and overall survival. RESULTS: Of the 18,113 patients meeting the inclusion criteria, 47% had elevated pretreatment carcinoembryonic antigen and 13% experienced pathological compete response. Elevated pretreatment carcinoembryonic antigen was independently associated with decreased pathological complete response (OR = 0.65, 95% CI = 0.52-0.77, p < 0.001), pathological tumor regression (OR = 0.74, 95% CI = 0.67-0.70, p < 0.001), tumor downstaging (OR = 0.77, 95% CI = 0.63-0.92, p < 0.001), and overall survival (HR = 1.45, 95% CI = 1.34-1.58, p < 0.001). CONCLUSION: Rectal cancer patients with elevated pretreatment carcinoembryonic antigen are less likely to experience pathological complete response, pathological tumor regression, and tumor downstaging after neoadjuvant treatment and experience decreased survival. These patients may not be suitable candidates for an observational "watch-and-wait" strategy. Future prospective studies should investigate the relationships between CEA levels, neoadjuvant treatment response, recurrence, and survival. PMID- 26546123 TI - Accelerated degradation of collagen membranes in diabetic rats is associated with increased infiltration of macrophages and blood vessels. AB - OBJECTIVES: Increased collagenolytic activity in diabetes may compromise collagen membrane (CM) survival. Tetracycline (TTC) possesses anti-collagenolytic properties and delays CM degradation. This study evaluated macrophage and capillary infiltration within CMs in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in 20 Wistar rats by streptozotocin and 20 served as controls. Biotin-labeled CM discs were immersed in either TTC (50 mg/ml) or PBS. In each animal, 2 discs (TTC and control) were implanted under the parietal periosteum and rats were sacrificed at 2 or 4 weeks post-implantation. The area and thickness of the residual disc collagen were measured following staining with streptavidin, and the number of macrophages and blood vessels within the membranes was determined using specific antibodies (to CD68 and transglutaminase II, respectively). RESULTS: Diabetes significantly reduced the area and thickness of the CMs, while TTC increased CM thickness significantly in both groups of rats at 2 and 4 weeks. Diabetes increased the number of macrophages (~eightfold at 2 weeks and ~fourfold at 4 weeks), but TTC had no significant effect. Finally, diabetes increased the number of blood vessels within the discs (~threefold at 2 weeks and ~twofold at 4 weeks), while TTC had no effect. CONCLUSIONS: Diabetes increases degradation of native CMs and the number of blood vessels and macrophages within them. TTC immersion delays CM degradation without an apparent effect on macrophage and blood vessel penetration. CLINICAL RELEVANCE: Enhanced CM degradation in diabetic conditions which impair guided regenerative procedure outcome is apparently related to increased blood vessel formation and macrophage infiltration. PMID- 26546124 TI - Functional, esthetical, and periodontal determination of the dentition in 35- to 44-year-old Brazilian adults. AB - AIMS: The aims of the present study were to evaluate oral health status among Brazilian adults aged 35 to 44 years with regard to functional dentition based on four different definitions and classify dentition configurations using a dental functional status classification system. METHODS: The sample was composed of 9564 individuals who participated in the 2010 National Oral Health Survey. The definitions were "well-distributed teeth" concept (WDT), the World Health Organization functional dentition concept (FDWHO), functional dentition classified by esthetics and occlusion (FDClass5), and functional dentition classified by esthetics, occlusion, and periodontal status (FDClass6). Dentitions were classified on six sequential, accumulative levels (anyone reaching level VI necessarily met the criteria on all previous levels): I->=one tooth in each arch; II->=10 teeth in each arch (WDT) or >=20 teeth present (FDWHO); III-all 12 anterior teeth present; IV->=3 premolar posterior occluding pairs (POPs) present; V->=one molar POP bilaterally (FDClass5); VI-all sextants with Community Periodontal Index <3 and/or loss of attachment <=1 (FDClass6). RESULTS: The prevalence rates of the different definitions of functional dentition ranged from 42.6 % (FDClass5) and 40.3 % (FDClass6) to 72.9 % (WDT) and 77.9 % (FDWHO). CONCLUSIONS: The oral health status of Brazilian adults exhibited considerable variation due to the different definitions of functional dentition, and less than half of Brazilian adults met all the criteria of function. CLINICAL RELEVANCE: The indication and planning of prosthetic rehabilitation should not only be based on the absence of teeth but also the distribution and periodontal status of the teeth present. PMID- 26546126 TI - Sources of inversion variation in the small single copy (SSC) region of chloroplast genomes. PMID- 26546125 TI - Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges. AB - BACKGROUND: Down syndrome (DS) or trisomy 21 is the result of a genetic dosage imbalance that translates in a broad clinical spectrum. A major challenge in the study of DS is the identification of functional genetic elements with wide impact on phenotypic alterations. Recently, miRNAs have been recognized as major contributors to several disease conditions by acting as post-transcriptional regulators of a plethora of genes. Five chromosome 21 (HSA21) miRNAs have been found overexpressed in DS individuals and could function as key elements in the pathophysiology. Interestingly, in the trisomic Ts65Dn DS mouse model two of these miRNAs (miR-155 and miR-802) are also triplicated and overexpressed in brain. RESULTS: In the current work, we interrogated the impact of miR-155 and miR-802 upregulation on the transcriptome of Ts65Dn brains. We developed a lentiviral miRNA-sponge strategy (Lv-miR155-802T) to identify in vivo relevant miR-155 and miR-802 target mRNAs. Hippocampal injections of lentiviral sponges in Ts65Dn mice normalized the expression of miR-155 and miR-802 and rescued the levels of their targets methyl-CpG-binding protein 2 gene (Mecp2), SH2 (Src homology 2)-containing inositol phosphatase-1 (Ship1) and Forkhead box protein M1 (FoxM1). Transcriptomic data of Lv-miR155-802T miRNA-sponge treated hippocampi correlated with candidate targets highlighting miRNA dosage-sensitive genes. Significant associations were found in a subset of genes (Rufy2, Nova1, Nav1, Thoc1 and Sumo3) that could be experimentally validated. CONCLUSIONS: The lentiviral miRNA-sponge strategy demonstrated the genome-wide regulatory effects of miR-155 and miR-802. Furthermore, the analysis combining predicted candidates and experimental transcriptomic data proved to retrieve genes with potential significance in DS-hippocampal phenotype bridging with DS other neurological associated diseases such as Alzheimer's disease. PMID- 26546127 TI - Divergent growth strategies between red algae and kelps influence biomechanical properties. AB - PREMISE OF THE STUDY: Morphology and material properties are the main components of the mechanical design of organisms, with species groups developing different optimization strategies in the context of their physical environment. For intertidal and subtidal seaweeds, possessing highly flexible and extensible tissues allows individuals to bend and reconfigure in flow, thereby reducing drag. Previous research has shown that aging may compromise these qualities. Tissue age increases with distance from the blade's meristem, which differs in its position on kelps and red algae. Here, we assess whether longitudinal patterns of blade material properties differ between these two algal groups according to tissue age. METHODS: We performed tensile tests on tissues samples excised from various positions along the extent of blades in nine kelp species (basal growth) and 15 species of red algae (apical growth). KEY RESULTS: We found that older tissues were less flexible and extensible than younger tissues in all species tested. As predicted, tissue near the basal meristem in kelp was more flexible and extensible than older tissue at the blade's distal end. The opposite pattern was observed for red algae, with the most flexible and extensible tissues found near the apical meristem at the distal ends of blades. CONCLUSIONS: We propose that divergent patterns in the distribution of material properties along blades may have different consequences for the performance of kelps and red algae. The positioning of younger tissues at the blade base for kelps may enable these species to attain larger body sizes in wave-swept habitats. PMID- 26546130 TI - Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle. AB - Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site-specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4-fold increase in its perfusion as well as a 2- to 4-fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By transdermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels. PMID- 26546129 TI - Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic beta-cell function via glycogen synthase kinase-3beta. AB - Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18-30 vs. 1.2-6.3%), independent of body mass index and antipsychotic medication, suggesting shared genetic components may contribute to both diseases. The cause of this association remains unknown. Mutations in disrupted in schizophrenia 1 (DISC1) increase the risk of developing psychiatric disorders [logarithm (base 10) of odds = 7.1]. Here, we identified DISC1 as a major player controlling pancreatic beta-cell proliferation and insulin secretion via regulation of glycogen synthase kinase 3beta (GSK3beta). DISC1 expression was enriched in developing mouse and human pancreas and adult beta- and ductal cells. Loss of DISC1 function, through siRNA mediated depletion or expression of a dominant-negative truncation that models the chromosomal translocation of human DISC1 in schizophrenia, resulted in decreased beta-cell proliferation (3 vs. 1%; P < 0.01), increased apoptosis (0.1 vs. 0.6%; P < 0.01), and glucose intolerance in transgenic mice. Insulin secretion was reduced (0.5 vs. 0.1 ng/ml; P < 0.05), and critical beta-cell transcription factors Pdx1 and Nkx6.1 were significantly decreased. Impaired DISC1 allowed inappropriate activation of GSK3beta in beta cells, and antagonizing GSK3beta (SB216763; IC50 = 34.3 nM) rescued the beta-cell defects. These results uncover an unexpected role for DISC1 in normal beta-cell physiology and suggest that DISC1 dysregulation contributes to T2D independently of its importance for cognition. PMID- 26546133 TI - Continuous scanning trials:Transitioning through the attractor landscape. AB - Bimanual 1:1 coordination patterns other than in-phase (0 degrees ) and anti phase (180 degrees ) have proven difficult to perform even with extended practice. The difficulty has traditionally been attributed to phase attraction that draws the coordination between the limbs towards the bimanual patterns of in phase and anti-phase and variability associated with the activation and associated proprioceptive signals of non-homologous muscles via crossed and uncrossed cortical pathways. However, recent experiments have demonstrated that a wide range of relative phase and multi-frequency coordination patterns can be effectively produced with only a few minutes of practice when Lissajous or online relative phase information is provided. The present experiment was designed to determine if participants provided Lissajous feedback comprised of continuously transitioning relative phase goals could be effectively performed as the participant navigates through the attractor landscape. The results clearly indicated that participants can effectively produce a large range of supposedly unstable coordination patterns (between 0 degrees and 180 degrees in 1 degrees increments) after only a few minutes of practice. These findings clearly indicate that the perception-action system is fully capable of effectively producing and transitioning through a wide range of bimanual coordination patterns and that the reason for the failure to produce these patterns in previous experiments resides in the perceptual information and attentional requirements typically found in experimental testing environments. PMID- 26546131 TI - Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation. AB - Alternative cleavage and polyadenylation (APA) plays a crucial role in the regulation of gene expression across eukaryotes. Although APA is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we used a rigorous subcellular fractionation approach to compare APA profiles of cytoplasmic and nuclear RNA fractions from human cell lines. This approach allowed us to extract APA isoforms that are subjected to differential regulation and provided us with a platform to interrogate the molecular regulatory pathways that shape APA profiles in different subcellular locations. Here, we show that APA isoforms with shorter 3' UTRs tend to be overrepresented in the cytoplasm and appear to be cell-type specific events. Nuclear retention of longer APA isoforms occurs and is partly a result of incomplete splicing contributing to the observed cytoplasmic bias of transcripts with shorter 3' UTRs. We demonstrate that the endoribonuclease III, DICER1, contributes to the establishment of subcellular APA profiles not only by expected cytoplasmic miRNA-mediated destabilization of APA mRNA isoforms, but also by affecting polyadenylation site choice. PMID- 26546134 TI - Key components in models of community-based interventions coordinating care in dementia: a mixed studies systematic review protocol. AB - BACKGROUND: Current health and social care systems are providing suboptimal and fragmented care to the growing dementia population. Interventions aiming to coordinate care services for individuals with dementia and their families are already widely used; however, the structure and implementation of these interventions vary. This mixed studies review aims to investigate the key components of effective community-based interventions that focus on coordinating care in dementia. METHODS: We will search MEDLINE, Cochrane Library, Embase and PsycINFO databases for studies of any design that look at community-based interventions that aim to coordinate dementia care through the allocation of a specified professional responsible for provision of care. Health Management Information Consortium (HMIC), Social Policy and Practice (SPP), ProQuest and International Clinical Trials Registry Platform (ICTRP) databases will be searched for grey literature. Outcomes of interest are health outcome measures that relate to the individual with dementia and/or informal caregiver, measures of resource use or process measures. Two independent reviewers will screen identified papers and extract data from eligible studies. Evidence synthesis will take place in three stages, and methods will be largely dependent on the data available. A sequential review design will be used where the qualitative evidence will be synthesised first, focusing on stakeholder's subjective views of key components. This will drive forward the quantitative stage which will identify key components of effective interventions. The final stage of the review will merge the two strands of evidence through a narrative synthesis. DISCUSSION: The results from this review will be used to develop a model for a community-based intervention coordinating care in dementia. Furthermore, the findings will help guide future work on intervention development of health and social care services for dementia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024618. PMID- 26546135 TI - Three-decade neurological and neurocognitive follow-up of HIV-1-infected patients on best-available antiretroviral therapy in Finland. AB - OBJECTIVES: Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986-1990, in 1997 and in 2013. SETTING: Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases. PARTICIPANTS: The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other. RESULTS: Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23-30) years. Blood CD4 cells at the diagnosis were 610 (29-870) cells/mm(3), and the nadir CD4 168 (4-408) cells/mm(3). The time on combined antiretroviral treatment was 13 (5-17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected. CONCLUSIONS: Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations. PMID- 26546136 TI - Application of three different sets of explicit criteria for assessing inappropriate prescribing in older patients: a nationwide prevalence study of ambulatory care visits in Taiwan. AB - OBJECTIVE: To investigate the national prevalence of potentially inappropriate medications (PIMs) prescribed in ambulatory care clinics in Taiwan according to three different sets of regional criteria and the correlates of PIM use. DESIGN: Cross-sectional study. SETTING: This analysis included older patients who visited ambulatory care clinics in 2009 and represented half of the older population included on the Taiwanese National Health Insurance Research Database. PARTICIPANTS: We identified 1,164,701 subjects who visited ambulatory care clinics and were over 65 years old in 2009. PRIMARY AND SECONDARY OUTCOME MEASURES: PIM prevalence according to the 2012 Beers criteria, the PIM-Taiwan criteria and the PRISCUS criteria was estimated separately, and characteristics of PIM users were explored. Multivariate logistic regression analysis was used to determine patient factors associated with the use of at least one PIM. Leading PIMs for each set of criteria were also listed. RESULTS: The prevalence of having at least one PIM at the patient level was highest with the Beers criteria (86.2%), followed by the PIM-Taiwan criteria (73.3%) and the PRISCUS criteria (66.9%). Polypharmacy and younger age were associated with PIM use for all three sets of criteria. The leading PIMs detected by the PIM-Taiwan and PRISCUS criteria were all included in the 2012 Beers criteria. Non-COX-selective non steroidal anti-inflammatory drugs in the Beers criteria and benzodiazepines in the PIM-Taiwan and PRISCUS criteria accounted for most leading PIMs. CONCLUSIONS: The prevalence of PIMs was high among older Taiwanese patients receiving ambulatory care visits. The prevalence of PIM and its associated factors varied according to three sets of criteria at the population level. PMID- 26546137 TI - Bad apples or spoiled barrels? Multilevel modelling analysis of variation in high risk prescribing in Scotland between general practitioners and between the practices they work in. AB - OBJECTIVES: Primary care high-risk prescribing causes significant harm, but it is unclear if it is largely driven by individuals (a 'bad apple' problem) or by practices having higher or lower risk prescribing cultures (a 'spoiled barrel' problem). The study aimed to examine the extent of variation in high-risk prescribing between individual prescribers and between the practices they work in. DESIGN, SETTING AND PARTICIPANTS: Multilevel logistic regression modelling of routine cross-sectional data from 38 Scottish general practices for 181,010 encounters between 398 general practitioners (GPs) and 26,539 patients particularly vulnerable to adverse drug events (ADEs) of non-steroidal anti inflammatory drugs (NSAIDs) due to age, comorbidity or co-prescribing. OUTCOME MEASURE: Initiation of a new NSAID prescription in an encounter between GPs and eligible patients. RESULTS: A new high-risk NSAID was initiated in 1953 encounters (1.1% of encounters, 7.4% of patients). Older patients, those with more vulnerabilities to NSAID ADEs and those with polypharmacy were less likely to have a high-risk NSAID initiated, consistent with GPs generally recognising the risk of NSAIDs in eligible patients. Male GPs were more likely to initiate a high-risk NSAID than female GPs (OR 1.73, 95% CI 1.39 to 2.16). After accounting for patient characteristics, 4.2% (95% CI 2.1 to 8.3) of the variation in high risk NSAID prescribing was attributable to variation between practices, and 14.2% (95% CI 11.4 to 17.3) to variation between GPs. Three practices had statistically higher than average high-risk prescribing, but only 15.7% of GPs with higher than average high-risk prescribing and 18.5% of patients receiving such a prescription were in these practices. CONCLUSIONS: There was much more variation in high-risk prescribing between GPs than between practices, and only targeting practices with higher than average rates will miss most high-risk NSAID prescribing. Primary care prescribing safety improvement should ideally target all practices, but encourage practices to consider and act on variation between prescribers in the practice. PMID- 26546138 TI - Healthcare utilisation by pregnant patients with asthma in South Korea: a cohort study using nationwide claims data. AB - OBJECTIVES: Few nationwide population-based studies have examined the burden of asthma during pregnancy. Here, we investigated the burden and medical treatment of asthma during pregnancy requiring healthcare utilisation in South Korea. DESIGN: Cohort study. SETTING: Nationwide insurance claims database. PARTICIPANTS: A total of 1,306,281 pregnant women who delivered in South Korea in 2009-2011. OUTCOMES: The prevalence and exacerbation rates of asthma requiring healthcare utilisation, and the prescription of antiasthmatic drugs during pregnancy. RESULTS: The prevalence of asthma requiring healthcare utilisation was 0.43% among pregnant women. Among those with asthma requiring healthcare utilisation, 6.9% were hospitalised and treated with systemic steroids and short acting beta2-agonists during pregnancy. Oral drugs were prescribed less during the third trimester than during the first trimester (all p values for trends were <0.001). A significant number of patients with asthma were likely to stop taking antiasthmatic drugs after becoming pregnant. CONCLUSIONS: The prevalence of asthma requiring healthcare utilisation during pregnancy was not very high. However, a significant number of women were likely to stop taking antiasthmatic drugs, and those who did tended to experience exacerbations. PMID- 26546139 TI - New onset diabetes after kidney transplantation in patients with autosomal dominant polycystic kidney disease: systematic review protocol. AB - INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with numerous cysts developing in bilateral kidneys. Meanwhile, ADPKD can also be regarded as a systemic disease because the cystic and non-cystic abnormalities could be identified in multiple organs in patients with ADPKD. Several lines of evidence suggest the risk of post transplant diabetes mellitus or new-onset diabetes after transplantation (NODAT) is higher in patients with ADPKD compared with non-ADPKD renal recipients, but the available results are conflicting. We describe the protocol of a systematic review and meta-analysis for investigating the risk of NODAT in patients with ADPKD. METHODS AND ANALYSIS: PubMed, EMBASE and The Cochrane Library will be searched. Cohort studies irrespective of language and publication status, comparing the incidence of NODAT in renal recipients with ADPKD and other kidney disease will be eligible. We will assess heterogeneity among studies. Along with 95% CIs, dichotomous data will be summarised as risk ratios; numbers needed to treat/harm and continuous data will be given as standard mean differences. Excluding outliers and testing small sample size studies if our results are robust, sensitivity analysis will be carried out. ETHICS AND DISSEMINATION: Ethical approval is not required because this study includes no confidential personal data or patient interventions. The review findings will be helpful in designing and implementing future studies and will be of interest to a wide range of readers, including healthcare professionals, researchers, health service managers and policymakers. The systematic review will be published in a peer reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: The study protocol has been registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42014009677. PMID- 26546140 TI - Barriers faced by healthcare professionals when managing falls in older people in Kuala Lumpur, Malaysia: a qualitative study. AB - OBJECTIVE: To explore the barriers faced by healthcare professionals (HCPs) in managing falls among older people (aged above 60 years) who have a high risk of falling. RESEARCH DESIGN: The study used a qualitative methodology, comprising 10 in-depth interviews and two focus group discussions. A semistructured topic guide was used to facilitate the interviews, which were audio recorded, transcribed verbatim and checked for accuracy. Data were analysed thematically using WeftQDA software. PARTICIPANTS: 20 HCPs who managed falls in older people. SETTING: This study was conducted at the Primary Care Clinic in the University Malaya Medical Centre (UMMC), Malaysia. RESULTS: Four categories of barriers emerged-these were related to perceived barriers for older people, HCPs' barriers, lack of caregiver support and healthcare system barriers. HCPs perceived that older people normalised falls, felt stigmatised, were fatalistic, as well as in denial regarding falls-related advice. HCPs themselves trivialised falls and lacked the skills to manage falls. Rehabilitation was impeded by premature decisions to admit older people to nursing homes. Lastly, there was a lack of healthcare providers as well as a dearth of fall education and training on fall prevention for HCPs. CONCLUSIONS: This study identified barriers that explain poor fall management in older people with a high risk of falls. The lack of structured fall prevention guidelines and insufficient training in fall management made HCPs unable to advise patients on how to prevent falls. The findings of this study warrant evidence-based structured fall prevention intervention targeted to patients as well as to HCPs. PMID- 26546141 TI - A multilevel analysis of mortality following acute myocardial infarction in Norway: do municipal health services make a difference? AB - OBJECTIVES: Studies link area features such as neighbourhood socioeconomic deprivation to poor health outcomes. However, there is a paucity of research based on representative data investigating the effects of area-level health services on mortality. This study examines the extent to which municipal health services account for municipal variation in all-cause and cardiovascular disease (CVD) mortality. We hypothesise that unfavourable municipal features (eg, fewer available places for rehabilitation) are associated with higher risk of mortality after accounting for patients' characteristics. DESIGN: Population data from Norwegian national/municipal registrars are analysed using multilevel logistic regression in this prospective cohort study. SETTING AND PARTICIPANTS: The analytic sample (9412 patients aged 18+ from 336 municipalities) constitutes 87.7% of the nationwide population of Norwegian adults who were hospitalised for acute myocardial infarction (AMI) in 2009 and discharged alive. PRIMARY OUTCOME MEASURES: All-cause and CVD mortality occurring within 365 days after the first day of hospitalisation for AMI. RESULTS: There was a small but significant variation at the municipal level in all-cause mortality (0.5%; intraclass correlation coefficient=0.005) but not CVD mortality. There were no significant fixed effects of municipal health services on mortality in bivariate models. Patients' characteristics (eg, gender, comorbidities) fully accounted for the observed municipal variation in mortality. Being male versus female (OR=1.21, 95% CI 1.02 to 1.43), or having been previously diagnosed with dementia versus not (OR=2.06, 95% CI 1.53 to 2.77) were also linked to higher odds of death. CONCLUSIONS: Municipal variation in all-cause mortality for Norwegian patients with AMI appears to be driven not by differences across municipalities in health service levels, but by differences across municipalities in the composition of patients. Focusing on chronic disease prevention and treatment, and tackling personal and structural risk factors embedded within patients' sociodemographic characteristics, may be especially beneficial for longevity. PMID- 26546142 TI - Ranolazine for the treatment of chronic stable angina: a cost-effectiveness analysis from the UK perspective. AB - OBJECTIVES: To estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing >=3 attacks/week. SETTING: An economic model utilising a UK health system perspective, a 1-month cycle-length and a 1-year time horizon. PARTICIPANTS: Patients with stable coronary disease experiencing >=3 attacks/week starting in 1 of 4 angina frequency health states based on Seattle Angina Questionnaire Angina Frequency (SAQAF) scores (100=no; 61 99=monthly; 31-60=weekly; 0-30=daily angina). INTERVENTION: Ranolazine added to SoC or SoC alone. Patients were allowed to transition between SAQAF states (first cycle only) or death (any cycle) based on probabilities derived from the randomised, controlled Efficacy of Ranolazine in Chronic Angina trial and other studies. Patients not responding to ranolazine in month 1 (not improving >=1 SAQAF health state) discontinued ranolazine and were assumed to behave like SoC patients. PRIMARY AND SECONDARY OUTCOMES MEASURES: Costs (L2014) and quality adjusted life-years (QALYs) for patients receiving and not receiving ranolazine. RESULTS: Ranolazine patients lived a mean of 0.701 QALYs at a cost of L5208. Those not receiving ranolazine lived 0.662 QALYs at a cost of L5318. The addition of ranolazine to SoC was therefore a dominant economic strategy. The incremental cost-effectiveness ratio was sensitive to ranolazine cost; exceeding L20,000/QALY when ranolazine's cost was >L203/month. Ranolazine remained a dominant strategy when indirect costs were included and mortality rates were assumed to increase with worsening severity of SAQAF health states. Monte Carlo simulation found ranolazine to be a dominant strategy in ~71% of 10,000 iterations. CONCLUSIONS: Although UK-specific data on ranolazine's efficacy and safety are lacking, our analysis suggest ranolazine added to SoC in patients with weekly or daily angina is likely cost-effective from a UK health system perspective. PMID- 26546143 TI - Associations of volume and other hospital characteristics on mortality within 30 days of acute myocardial infarction in South Korea. AB - OBJECTIVE: The mortality for acute myocardial infarction (AMI) has declined worldwide. However, improvements in care for AMI in South Korea have lagged slightly behind those in other countries. Therefore, it is important to investigate how factors such as hospital volume, structural characteristics of hospital and hospital staffing level affect 30-day mortality due to AMI in South Korea. SETTING: We used health insurance claim data from 114 hospitals to analyse 30-day mortality for AMI. PARTICIPANTS: These data consisted of 19,638 hospitalisations during 2010-2013. INTERVENTIONS: No interventions were made. OUTCOME MEASURE: Multilevel models were analysed to examine the association between the 30-day mortality and inpatient and hospital level variables. RESULTS: In the 30 days after hospitalisation, 10.5% of patients with AMI died. Hospitalisation cases at hospitals with a higher AMI volume had generally inverse associations with 30-day mortality (1st quartile=ref; 2nd quartile=OR 0.811, 95% CI 0.658 to 0.998, 3rd quartile=OR 0.648, 95% CI 0.500 to 0.840, 4th quartile=OR 0.807, 95% CI 0.573 to 1.138). In addition, hospitals with a greater proportion of specialists were associated with better outcomes (above median=OR 0.789, 95% CI 0.663 to 0.940). CONCLUSIONS: Health policymakers need to include volume and staffing when defining the framework for treatment of AMI in South Korean hospitals. Otherwise, they must consider increasing the proportion of specialists or regulating the hiring of emergency medicine specialists. In conclusion, they must make an effort to reduce 30-day mortality following AMI based on such considerations. PMID- 26546144 TI - Do marginal investments made by NHS healthcare commissioners in the UK produce the outcomes they hope to achieve? Observational study. AB - OBJECTIVE: To investigate the effect of targeted marginal annual investments by local healthcare commissioners on the outcomes they expected to achieve with these investments. DESIGN: Controlled before and after study. SETTING: 152 commissioning organisations (primary care trusts) in England. METHODS: National surveys of commissioning managers in 2009 and 2010 to identify: the largest marginal investments made in four key conditions/services (diabetes, coronary heart disease, chronic pulmonary airways disease and emergency and urgent care) in 2008/2009 and 2009/2010; the outcomes commissioners expected to achieve with these investments; and the processes commissioners used to develop these investments. Collation of routinely available data on outcomes commissioners expected from these investments over the period 2007/2008 to 2010/2011. RESULTS: 51% (77/152) of commissioners agreed to participate in the survey in 2009 and 60% (91/152) in 2010. Around half reported targeted marginal investments in each condition/service each year. Routine data on many of the outcomes they expected to achieve through these investments were not available. Also, commissioners expected some outcomes to be achieved beyond the time scale of our study. Therefore, only a limited number of outcomes of investments were tested. Outcomes included directly standardised emergency admission rates for the four conditions/services, and the percentage of patients with diabetes with glycated haemoglobin <7. There was no evidence that targeted marginal investments reduced emergency admission rates. There was evidence of an improvement in blood glucose management for diabetes for commissioners investing to improve diabetes care but this was compromised by a change in how the outcome was measured in different years. This investment was unlikely to be cost-effective. CONCLUSIONS: Commissioners made marginal investments in specific health conditions and services with the aim of improving a wide range of outcomes. There was little evidence of impact on the limited number of outcomes measured. PMID- 26546145 TI - Examination of the community-specific prevalence of and factors associated with substance use and misuse among Rural and Urban adolescents: a cross-sectional analysis in Bosnia and Herzegovina. AB - OBJECTIVE: The community of residence (ie, urban vs rural) is one of the known factors of influence on substance use and misuse (SUM). The aim of this study was to explore the community-specific prevalence of SUM and the associations that exist between scholastic, familial, sports and sociodemographic factors with SUM in adolescents from Bosnia and Herzegovina. METHODS: In this cross-sectional study, which was completed between November and December 2014, the participants were 957 adolescents (aged 17 to 18 years) from Bosnia and Herzegovina (485; 50.6% females). The independent variables were sociodemographic, academic, sport and familial factors. The dependent variables consisted of questions on cigarette smoking and alcohol consumption. We have calculated differences between groups of participants (gender, community), while the logistic regressions were applied to define associations between the independent and dependent variables. RESULTS: In the urban community, cigarette smoking is more prevalent in girls (OR=2.05; 95% CI 1.27 to 3.35), while harmful drinking is more prevalent in boys (OR=2.07; 95% CI 1.59 to 2.73). When data are weighted by gender and community, harmful drinking is more prevalent in urban boys (OR=1.97; 95% CI 1.31 to 2.95), cigarette smoking is more frequent in rural boys (OR=1.61; 95% CI 1.04 to 2.39), and urban girls misuse substances to a greater extent than rural girls (OR=1.70; 95% CI 1.16 to 2.51,OR=2.85; 95% CI 1.88 to 4.31,OR=2.78; 95% CI 1.67 to 4.61 for cigarette smoking, harmful drinking and simultaneous smoking-drinking, respectively). Academic failure is strongly associated with a higher likelihood of SUM. The associations between parental factors and SUM are more evident in urban youth. Sports factors are specifically correlated with SUM for urban girls. CONCLUSIONS: Living in an urban environment should be considered as a higher risk factor for SUM in girls. Parental variables are more strongly associated with SUM among urban youth, most probably because of the higher parental involvement in children' personal lives in urban communities (ie, college plans, for example). Specific indicators should be monitored in the prevention of SUM. PMID- 26546146 TI - Prediction of individual combined benefit and harm for patients with atrial fibrillation considering warfarin therapy: a study protocol. AB - INTRODUCTION: Clinical prediction rules have been validated and widely used in patients with atrial fibrillation (AF) to predict stroke and major bleeding. However, these prediction rules were not developed in the same population, and do not provide the key information that patients and prescribers need at the time anticoagulants are being considered-what is the individual patient-specific risk of both benefit (decreased stroke) and harm (increased major bleeding). In this study, our primary objective is to develop and validate a prediction model for patients' individual combined benefit and harm outcomes (stroke, major bleeding and neither event) with and without warfarin therapy. Our secondary outcome is all-cause mortality. METHODS AND ANALYSIS: We will use data from the Kaiser Permanente Colorado (KPCO) anticoagulation management databases and electronic medical records. Patients with a primary or secondary diagnosis during an ambulatory KPCO medical office visit, emergency department visit, or inpatient stay between 1 January 2005 and 31 December 2012 with no AF diagnosis in the previous 180 days will be included. Patients' demographic characteristics, laboratory data, comorbidities, warfarin medication data and concurrent use of medication will be used to construct the prediction model. For primary outcomes (stroke with no major bleeding, and major bleeding with no stroke), we will perform polytomous logistic regression to develop a prediction model for patients' individual combined benefit and harm outcomes, taking neither event group as the reference group. As regards death, we will use Cox proportional hazards regression analysis to build a prediction model for all-cause mortality. ETHICS AND DISSEMINATION: This study has been approved by the KPCO Institutional Review Board and the Hamilton Integrated Research Ethics Board. Results from this study will be published in a peer-reviewed journal electronically and in print. The prediction models may aid in patient-physician shared decision-making when they are considering warfarin therapy. PMID- 26546147 TI - Protocol for a process-oriented qualitative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme using the Researcher-in-Residence model. AB - INTRODUCTION: The integration of health and social care in England is widely accepted as the answer to fragmentation, financial concerns and system inefficiencies, in the context of growing and ageing populations with increasingly complex needs. Despite an expanding body of literature, there is little evidence yet to suggest that integrated care can achieve the benefits that its advocates claim for it. Researchers have often adopted rationalist and technocratic approaches to evaluation, treating integration as an intervention rather than a process. Results have usually been of limited use to practitioners responsible for health and social care integration. There is, therefore, a need to broaden the evidence base, exploring not only what works but also how integrated care can most successfully be implemented and delivered. For this reason, we are carrying out a formative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme. Our expectation is that this will add value to the literature by focusing on the processes by which the vision and objectives of integrated care are translated through phases of development, implementation and delivery from a central to a local perspective, and from a strategic to an operational perspective. METHODS AND ANALYSIS: The qualitative and process-oriented evaluation uses an innovative participative approach-the Researcher-in-Residence model. The evaluation is underpinned by a critical ontology, an interpretive epistemology and a critical discourse analysis methodology. Data will be generated using interviews, observations and documentary gathering. ETHICS AND DISSEMINATION: Emerging findings will be interpreted and disseminated collaboratively with stakeholders, to enable the research to influence and optimise the effective implementation of integrated care across WELC. Presentations and publications will ensure that learning is shared as widely as possible. The study has received ethical approval from University College London's Research Ethics Committee and has all appropriate NHS governance clearances. PMID- 26546148 TI - What are the effects of varenicline compared with nicotine replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study. AB - INTRODUCTION: Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. METHODS: In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180,000. Follow-up will end with the earliest of either an 'event' or censoring due to the end of registration or death. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. This project has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences. PMID- 26546149 TI - Inhibition of TNF-alpha protects in vitro brain barrier from ischaemic damage. AB - Cerebral ischaemia, associated with neuroinflammation and oxidative stress, is known to perturb blood-brain barrier (BBB) integrity and promote brain oedema formation. Using an in vitro model of human BBB composed of brain microvascular endothelial cells and astrocytes, this study examined whether suppression of TNF alpha, a potent pro-inflammatory cytokine, might attenuate ischaemia-mediated cerebral barrier damage. Radical decreases in transendothelial electrical resistance and concomitant increases in paracellular flux across co-cultures exposed to increasing periods of oxygen-glucose deprivation alone (0.5-20 h) or followed by 20 h of reperfusion (OGD +/- R) confirmed the deleterious effects of ischaemic injury on cerebral barrier integrity and function which concurred with reductions in tight junction protein (claudin-5 and occludin) expressions. OGD +/ R elevated TNF-alpha secretion, NADPH oxidase activity, O2(-) production, actin stress fibre formation, MMP-2/9 activities and apoptosis in both endothelial cells and astrocytes. Increases in MMP-2 activity were confined to its extracellular isoform and treatments with OGD+R in astrocytes where MMP-9 could not be detected at all. Co-exposure of individual cell lines or co-cultures to an anti-TNF-alpha antibody dramatically diminished the extent of OGD +/- R-evoked oxidative stress, morphological changes, apoptosis, MMP-2/9 activities while improving the barrier function through upregulation of tight junction protein expressions. In conclusion, vitiation of the exaggerated release of TNF-alpha may be an important therapeutic strategy in preserving cerebral integrity and function during and following a cerebral ischaemic attack. PMID- 26546150 TI - Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling. AB - Neurotrophins, essential regulators of many aspects of neuronal differentiation and function, signal via four receptors, p75, TrkA, TrkB and TrkC. The three Trk paralogs are members of the LIG superfamily of membrane proteins, which share extracellular domains consisting of leucine-rich repeat and C2 Ig domains. Another LIG protein, LINGO-1 has been reported to bind and influence signaling of p75 as well as TrkA, TrkB and TrkC. Here we examine the manner in which LINGO-1 influences the function of TrkA, TrkB and TrkC. We report that Trk activation promotes Trk association with LINGO-1, and that this association promotes Trk degradation by a lysosomal mechanism. This mechanism resembles the mechanism by which another LIG protein, LRIG1, promotes lysosomal degradation of receptor tyrosine kinases such as the EGF receptor. We present evidence indicating that the Trk/LINGO-1 interaction occurs, in part, within recycling endosomes. We show that a mutant form of LINGO-1, with much of the extracellular domain deleted, has the capacity to enhance TrkA signaling in PC12 cells, possibly by acting as an inhibitor of Trk down-regulation by full length LINGO-1. We propose that LINGO-1 functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including TrkA, TrkB and TrkC. PMID- 26546151 TI - Differences in the design and sale of e-cigarettes by cigarette manufacturers and non-cigarette manufacturers in the USA. AB - BACKGROUND: Three categories of e-cigarette brands have emerged within the US market: e-cigarette brands developed by cigarette manufacturers, brands acquired by cigarette manufacturers and brands with no cigarette manufacturer affiliation. In the absence of federal regulatory oversight of e-cigarettes, we assessed differences in e-cigarette products and sales practices across these categories. METHODS: Brand websites for top-selling e-cigarette brands from each of these categories were examined in October of 2015 to compare website access restrictions, online sales practices and products sold, including e-cigarette model type (eg, 'cigalike' vs advanced systems) and options available (eg, flavoured, nicotine free). RESULTS: Website access to brands developed by cigarette manufacturers was restricted to users aged 21 years or older, and one website required user registration. In addition, these brands were exclusively reusable/rechargeable 'cigalikes.' Limited flavour options were available for these products, and nicotine-free options were not sold. In contrast, brands acquired by cigarette manufacturers and brands with no cigarette manufacturer affiliation generally required website visitors to be 18, offered a nicotine-free option, and most offered disposable products and an array of flavoured products (eg, fruit/candy flavours). CONCLUSIONS: This exploratory study finds differences in e-cigarette products and sales practices across these three e-cigarette brand categories, with brands developed by cigarette manufacturers adopting a particularly distinctive product and sales strategy. Anticipated regulation of e cigarettes in the USA may be influencing these product and sales decisions. PMID- 26546152 TI - Quantifying how smokers value attributes of electronic cigarettes. AB - INTRODUCTION: Rates of electronic cigarette (e-cigarette) use have increased quickly among US adults (3.3% in 2010 to 8.5% in 2013) and youth (4.5% in 2013 to 13.4% in 2014). As state and local governments consider regulatory policies, understanding what smokers believe about e-cigarettes and how they value e cigarettes is important. METHODS: Using data from a convenience sample of Florida adult smokers (N=765), we investigated the value smokers place on specific attributes of e-cigarettes (availability of flavours, effectiveness of e cigarettes as a cessation aid, healthier alternative to regular cigarettes, ability to use e-cigarettes in public places) by asking smokers how much they would be willing to pay for e-cigarettes with and without each of these attributes. RESULTS: For cigarette-only and dual users, losing the ability to use an e-cigarette as a quit aid and losing the harm reduction of an e-cigarette significantly reduced the price respondents were willing to pay for an e cigarette. For cigarette-only users, not being able to use an e-cigarette indoors and losing flavours also significantly reduced the price respondents were willing to pay for an e-cigarette. CONCLUSION: Our results suggest that smokers value multiple attributes of e-cigarettes. Our valuation measures also appear to align with smokers' beliefs about e-cigarettes. PMID- 26546153 TI - Electronic cigarette marketers manipulate antitobacco advertisements to promote vaping. PMID- 26546154 TI - Multiple approaches for the detection and characterization of viral and plasmid symbionts from a collection of marine fungi. AB - The number of reported mycoviruses is increasing exponentially due to the current ability to detect mycoviruses using next-generation sequencing (NGS) approaches, with a large number of viral genomes built in-silico using data from fungal transcriptome projects. We decided to screen a collection of fungi originating from a specific marine environment (associated with the seagrass Posidonia oceanica) for the presence of mycoviruses: our findings reveal a wealth of diversity among these symbionts and this complexity will require further studies to address their specific role in this ecological niche. In specific, we identified twelve new virus species belonging to nine distinct lineages: they are members of megabirnavirus, totivirus, chrysovirus, partitivirus and five still undefined clades. We showed evidence of an endogenized virus ORF, and evidence of accumulation of dsRNA from metaviridae retroviral elements. We applied different techniques for detecting the presence of mycoviruses including (i) dsRNA extraction and cDNA cloning, (ii) small and total RNA sequencing through NGS techniques, (iii) rolling circle amplification (RCA) and total DNA extraction analyses, (iv) virus purifications and electron microscopy. We tried also to critically evaluate the intrinsic value and limitations of each of these techniques. Based on the samples we could compare directly, RNAseq analysis is superior to sRNA for de novo assembly of mycoviruses. To our knowledge this is the first report on the virome of fungi isolated from marine environment. The GenBank/eMBL/DDBJ accession numbers of the sequences reported in this paper are: KT601099-KT601110; KT601114-KT601120; KT592305; KT950836-KT950841. PMID- 26546155 TI - La Piedad Michoacan Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation. AB - La Piedad Michoacan Mexico Virus (LPMV) is a member of the Rubulavirus genus within the Paramyxoviridae family. LPMV is the etiologic agent of "blue eye disease", causing a significant disease burden in swine in Mexico with long-term implications for the agricultural industry. This virus mainly affects piglets and is characterized by meningoencephalitis and respiratory distress. It also affects adult pigs, causing reduced fertility and abortions in females, and orchitis and epididymitis in males. Viruses of the Paramyxoviridae family evade the innate immune response by targeting components of the interferon (IFN) signaling pathway. The V protein, expressed by most paramyxoviruses, is a well characterized IFN signaling antagonist. Until now, there were no reports on the role of the LPMV-V protein in inhibiting the IFN response. In this study we demonstrate that LPMV-V protein antagonizes type I but not type II IFN signaling by binding STAT2, a component of the type I IFN cascade. Our results indicate that the last 18 amino acids of LPMV-V protein are required for binding to STAT2 in human and swine cells. While LPMV-V protein does not affect the protein levels of STAT1 or STAT2, it does prevent the IFN-induced phosphorylation and nuclear translocation of STAT1 and STAT2 thereby inhibiting cellular responses to IFN alpha/beta. PMID- 26546156 TI - Cationic antimicrobial peptide, magainin down-regulates secretion of pro inflammatory cytokines by early placental cytotrophoblasts. AB - BACKGROUND: Human placental villous cytotrophoblasts exhibit relative externalization of negatively charged moieties to the outer leaflet of the plasma membrane during the time of syncytialization rendering their reactivity to positively charged cationic antimicrobial peptides (CAMPs) during the window of implantation and early placentation. Vaginal administration of a synthetic CAMP, Ala(8,13,18)-magainin II amide (AMA) inhibited blastocyst implantation and early placentation in monkeys. Furthermore, the administration of AMA resulted in significant inhibition of cell differentiation, enhancement in apoptosis and loss of viability in first trimester placental villous cytotrophoblasts in primary culture. The present study examines the effect of in vitro application of different doses (0, 1, 10, 100, 1000 ng/ml) of AMA on the secreted cytokine profiles of cytotrophoblasts obtained from placental villi samples (n = 13) collected during 8-9 weeks of gestation and grown on three-dimensional collagen matrix in vitro. METHODS: A panel of forty-eight (48) cytokines in conditioned medium was analysed using multiplex immunoassays technique. Further, the steady state transcript levels of four cytokines (CCL4, CCL5, IL1B, IL6), the concentrations of which were affected by AMA in the isolated cytotrophoblasts, as well as, two cytokines (IL1A and TNF) which were not affected by AMA were estimated. Input list of cytokines secreted by cytotrophoblasts and showing differential secretion in response to AMA were used in enrichment analysis for the generation of biological networks. RESULTS: Placental cytotrophoblasts secreted 27 cytokines, 13 of which are affected by AMA in vitro with significantly decreased secretion of CCLs-2, 3, 4, 5, CXCLs-1 and 8, FGF2 and MCSF and that of IL1B, IL6 and MIF, and increased secretion of IL16 and IL-2RA. Of the above cytokines showing differential secretion, only IL-2RA, IL16 and MIF showed significant correspondence in the steady state expression of their respective transcript levels. Post-hoc Enrichment analysis revealed Toll-like receptor (TLR) mediated pathways were the top-scored target pathways that were affected by AMA. CONCLUSIONS: Administration of a CAMP causes shift in the balance of immune-inflammatory responses involving downstream pathways of TLRs in cytotrophoblast function. Further verification of functions of placental trophoblasts on administration of CAMP with pregnancy outcome is necessary. PMID- 26546157 TI - The Swedish fracture register: 103,000 fractures registered. AB - BACKGROUND: Although fractures consume large social and financial resources, little is known about their actual numbers, treatment methods or outcomes. The scarcity of data calls for a high-quality, population-based register. No previous registers have prospectively collected data and patient-reported outcome measures (PROMs) on fractures of all types. The Swedish Fracture Register was recently created to fill this gap in knowledge. Its purpose is to provide information on fractures of all types, whether treated by surgery or otherwise. The aim of this article is to describe how the register was developed and its current use. DESCRIPTION: The Swedish Fracture Register was developed during a 4-year period, 2007-2010. Data collection started in 2011. The register currently collects data on all extremity, pelvic and spine fractures in adults who have been diagnosed or treated at the affiliated departments. Data entry is fully web based, including date, cause of injury, classification and treatment. It is performed by the attending physician. Patients fill out PROMs - EQ-5D-3L and the Short Musculoskeletal Function Assessment (SMFA) - relating to health status and level of functioning before the fracture and one year later. Surgeon-reported outcome measures are registered as reoperation rates. The Swedish Fracture Register is now functioning effectively and is used in clinical routine. From January 2011 to September 2015, more than 103,000 fractures have been entered at 26 Swedish orthopedic departments. CONCLUSIONS: The Swedish Fracture Register is already a well-functioning, population-based fracture register that covers fractures of all types, regardless of treatment, and collects both surgeon- and patient-reported outcome measures. In the future the Swedish Fracture Register will be able to present both results of fracture treatment and valuable epidemiological data. PMID- 26546158 TI - Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia. AB - The AML1/ETO fusion protein is essential to the development of t(8;21) acute myeloid leukemia (AML) and is well recognized for its dominant-negative effect on the coexisting wild-type protein AML1. However, the genome-wide interplay between AML1/ETO and wild-type AML1 remains elusive in the leukemogenesis of t(8;21) AML. Through chromatin immunoprecipitation sequencing and computational analysis, followed by a series of experimental validations, we report here that wild-type AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed; this is achieved via forming a complex with AML1/ETO and via recruiting the cofactor AP-1 on chromatin. On chromatin occupancy, AML1/ETO and wild-type AML1 largely overlap and preferentially bind to adjacent and distinct short and long AML1 motifs on the colocalized regions, respectively. On physical interaction, AML1/ETO can form a complex with wild-type AML1 on chromatin, and the runt homology domain of both proteins are responsible for their interactions. More importantly, the relative binding signals of AML1 and AML1/ETO on chromatin determine which genes are repressed or activated by AML1/ETO. Further analysis of coregulators indicates that AML1/ETO transactivates gene expression through recruiting AP-1 to the AML1/ETO-AML1 complex. These findings enrich our knowledge of understanding the significance of the interplay between the wild-type protein and the oncogenic fusion protein in the development of leukemia. PMID- 26546159 TI - Temporomandibular joint ankylosis in a child: an unusual case with delayed surgical intervention. AB - BACKGROUND: The Temporomandibular Joint (TMJ) ankylosis in child is rare and yet the causes still remain unclear. This condition that affects the feeding and possible airway obstruction do not only worry the parents, but also possesses as a great challenge to the surgeons. Furthermore, it interferes with the facial skeletal and dento-alveolar development in the on growing child. CASE PRESENTATION: In this case report, we presented the management of a 7 year old with left TMJ ankylosis discovered since infant. Clinical and imaging investigations were consistent with left temporomandibular joint ankylosis (Type IV) possible secondary to childhood septic arthritis. Left gap arthroplasty via modified Al Kayat Bramley and retromandibular approach was performed, with interpositional arthroplasty placement of temporalis fascia graft. No complications from the surgery except reduced mouth opening were seen. Possible contributing factors to this less than satisfactory mouth opening are adressed. CONCLUSION: We describe here, an unusual childhood temporomandibular joint ankylosis possible due to septic arthritis with delayed surgical intervention. The aetiology, classifications, timing and choice of surgical techniques along with its considerations and complications are discussed. Although there is no consensus on the surgical treatment of TMJ ankylosis, early mobilisation, aggressive physiotherapy and close follow-up are advocated by many authors for successful treatment. PMID- 26546160 TI - Development of a fluorescence-based multiplex genotyping method for simultaneous determination of human papillomavirus infections and viral loads. AB - BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing intraepithelial lesion or malignancy (NILM). The aims of the current study is to establish a method named BioPerfectus Multiplex Real Time (BMRT) HPV assay for simultaneous typing and quantifying HPVs, and to evaluate it by comparison with HPV GenoArray test and PCR-sequencing method, as well as histological status. METHODS: A total of 817 cervical specimens were evaluated by BMRT method and HPV GenoArray test, using PCR-sequencing method as the reference standard; simultaneously, high-risk HPV-16 and -18 DNA loads were assessed in 443 specimens to investigate the correlation with infection outcomes. RESULTS: The overall detection coincidence rate between BMRT assay and HPV GenoArray test is 96.6 % and the Kappa value is 0.760. In addition, the sensitivity and positive predictive value of BMRT is 98.4 % and 95.7 % compared with the results detected by PCR-sequencing method, respectively. HPV-16 viral load has a correlation with CINs or worse lesions. By comparing with infected women presenting NILM /cervicitis, the cutoff value for HPV-16 from patients with CINs was 0.827. With this cutoff value, 74.6 % sensitivity and 72.5 % specificity for prediction of HPV-16 infected patients with CINI and higher CIN were achieved. High significance was obtained when comparing the infected women presenting NILM/cervicitis with women either with CIN and cervical carcinomas (p < 0.001). CONCLUSIONS: The BMRT assay seemed to be a good alternative approach for HR-HPV testing, due to its high level of automation and ability to quantify HPV-16, HPV-18 and other HR-HPVs. PMID- 26546162 TI - Acupuncture in physiotherapy: a contemporary UK perspective. PMID- 26546161 TI - The influence of intestinal parasites on Plasmodium vivax-specific antibody responses to MSP-119 and AMA-1 in rural populations of the Brazilian Amazon. AB - BACKGROUND: Polyparasitism is a common condition in humans but its impact on the host immune system and clinical diseases is still poorly understood. There are few studies of the prevalence and the effect of malaria-intestinal parasite co infections in the immune response to malaria vaccine candidates. The present study determines whether the presence of malaria and intestinal parasites co infection is associated with impaired IgG responses to Plasmodium vivax AMA-1 and MSP-119 in a rural population of the Brazilian Amazon. METHODS: A cross-sectional survey was performed in a rural area of Rondonia State and 279 individuals were included in the present study. At recruitment, whole blood was collected and Plasmodium and intestinal parasites were detected by microscopy and molecular tests. Blood cell count and haemoglobin were also tested and antibody response specific to P. vivax AMA-1 and MSP-119 was measured in plasma by ELISA. The participants were grouped according to their infection status: singly infected with Plasmodium (M); co-infected with Plasmodium and intestinal parasites (CI); singly infected with intestinal parasites (IP) and negative (N) for both malaria and intestinal parasites. RESULTS: The prevalence of intestinal parasites was significantly higher in individuals with malaria and protozoan infections were more prevalent. IgG antibodies to PvAMA-1 and/or PvMSP-119 were detected in 74 % of the population. The prevalence of specific IgG was similar for both proteins in all four groups and among the groups the lowest prevalence was in IP group. The cytophilic sub-classes IgG1 and IgG3 were predominant in all groups for PvAMA 1 and IgG1, IgG3 and IgG4 for PvMSP-119. In the case of non-cytophilic antibodies to PvAMA-1, IgG2 was significantly higher in IP and N group when compared to M and CI while IgG4 was higher in IP group. CONCLUSIONS: The presence of intestinal parasites, mainly protozoans, in malaria co-infected individuals does not seem to alter the antibody immune responses to P. vivax AMA-1 and MSP-119. However, IgG response to both AMA1 and MSP1 were lower in individuals with intestinal parasites. PMID- 26546163 TI - Dry needling versus acupuncture: the ongoing debate. AB - Although Western medical acupuncture (WMA) is commonly practised in the UK, a particular approach called dry needling (DN) is becoming increasingly popular in other countries. The legitimacy of the use of DN by conventional non-physician healthcare professionals is questioned by acupuncturists. This article describes the ongoing debate over the practice of DN between physical therapists and acupuncturists, with a particular emphasis on the USA. DN and acupuncture share many similarities but may differ in certain aspects. Currently, little information is available from the literature regarding the relationship between the two needling techniques. Through reviewing their origins, theory, and practice, we found that DN and acupuncture overlap in terms of needling technique with solid filiform needles as well as some fundamental theories. Both WMA and DN are based on modern biomedical understandings of the human body, although DN arguably represents only one subcategory of WMA. The increasing volume of research into needling therapy explains its growing popularity in the musculoskeletal field including sports medicine. To resolve the debate over DN practice, we call for the establishment of a regulatory body to accredit DN courses and a formal, comprehensive educational component and training for healthcare professionals who are not physicians or acupuncturists. Because of the close relationship between DN and acupuncture, collaboration rather than dispute between acupuncturists and other healthcare professionals should be encouraged with respect to education, research, and practice for the benefit of patients with musculoskeletal conditions who require needling therapy. PMID- 26546164 TI - Elevated carbon dioxide increases soil nitrogen and phosphorus availability in a phosphorus-limited Eucalyptus woodland. AB - Free-air CO2 enrichment (FACE) experiments have demonstrated increased plant productivity in response to elevated (e)CO2, with the magnitude of responses related to soil nutrient status. Whilst understanding nutrient constraints on productivity responses to eCO2 is crucial for predicting carbon uptake and storage, very little is known about how eCO2 affects nutrient cycling in phosphorus (P)-limited ecosystems. Our study investigates eCO2 effects on soil N and P dynamics at the EucFACE experiment in Western Sydney over an 18-month period. Three ambient and three eCO2 (+150 ppm) FACE rings were installed in a P limited, mature Cumberland Plain Eucalyptus woodland. Levels of plant accessible nutrients, evaluated using ion exchange resins, were increased under eCO2, compared to ambient, for nitrate (+93%), ammonium (+12%) and phosphate (+54%). There was a strong seasonality to responses, particularly for phosphate, resulting in a relatively greater stimulation in available P, compared to N, under eCO2 in spring and summer. eCO2 was also associated with faster nutrient turnover rates in the first six months of the experiment, with higher N (+175%) and P (+211%) mineralization rates compared to ambient rings, although this difference did not persist. Seasonally dependant effects of eCO2 were seen for concentrations of dissolved organic carbon in soil solution (+31%), and there was also a reduction in bulk soil pH (-0.18 units) observed under eCO2. These results demonstrate that CO2 fertilization increases nutrient availability - particularly for phosphate - in P-limited soils, likely via increased plant belowground investment in labile carbon and associated enhancement of microbial turnover of organic matter and mobilization of chemically bound P. Early evidence suggests that there is the potential for the observed increases in P availability to support increased ecosystem C-accumulation under future predicted CO2 concentrations. PMID- 26546166 TI - Genetics meets epigenetics: Genetic variants that modulate noncoding RNA in cardiovascular diseases. AB - After the recent description of the human genome by the ENCODE and the FANTOM consortia, major attention has been addressed to the so-called "genomic noise", which mainly consists of noncoding RNAs (ncRNAs). Among them, microRNAs and long non-coding RNAs have been demonstrated to modulate gene expression and to be involved in several human diseases. Since ncRNAs and their targets are encoded in the genome, genetic principles apply. Common variants are supposed to influence the expression level and the functionality of ncRNAs, with subsequent differential regulation of their target genes. Moreover, several reports showed that polymorphisms in ncRNA or their target genes play a role in the development of cardiovascular adverse phenotype. Here, we provide an overview of the effects of these variations in cardiovascular diseases. PMID- 26546165 TI - Regulation of autophagy by Beclin 1 in the heart. AB - Dysregulation of autophagy in cardiomyocytes is implicated in various heart disease conditions. Beclin 1, a mammalian ortholog of yeast Atg6 and a core component of the autophagy machinery, plays a central role in the regulation of autophagy through activation of Vps34. Beclin 1's ability to activate Vps34 is tightly regulated via transcriptional regulation, miRNA, post-translational modification, and interaction with Beclin 1 binding proteins. Of these mechanisms, binding of Beclin 1 with Bcl-2 family proteins (Bcl-2/XL) that negatively regulate autophagy activity has been shown to be both positively and negatively regulated by various kinases, including DAPK, ROCK1, Mst1 and JNK1, in response to external stimuli. Beclin 1's interaction with Bcl-2/XL also secondarily affects apoptosis through regulation of pro-apoptotic BH3 domain containing proteins. Thus, modulation of Beclin 1 significantly influences both autophagy and apoptosis, thereby deeply affecting the survival and death of cardiomyocytes in the heart. In this review, we discuss the signaling mechanism of autophagy modulation through Beclin 1 and therapeutic potential of Beclin 1 in heart diseases. PMID- 26546167 TI - [Comparability study of analytical results between a group of clinical laboratories]. AB - OBJECTIVE: To describe the study of the comparability of the measurements levels of biological tests processed in biochemistry in Catlab's 4 laboratories. MATERIAL AND METHODS: Quality requirements, coefficients of variation and total error (CV% and TE %) were established. Controls were verified with the precision requirements (CV%) in each test and each individual laboratory analyser. Fresh serum samples were used for the comparability study. The differences were analysed using a Microsoft Access(r) application that produces modified Bland Altman plots. RESULTS: The comparison of 32 biological parameters that are performed in more than one laboratory and/or analyser generated 306 Bland-Altman graphs. Of these, 101 (33.1%) fell within the accepted range of values based on biological variability, and 205 (66.9%) required revision. Data were re-analysed based on consensus minimum specifications for analytical quality (consensus of the Asociacion Espanola de Farmaceuticos Analistas (AEFA), the Sociedad Espanola de Bioquimica Clinica y Patologia Molecular (SEQC), the Asociacion Espanola de Biopatologia Medica (AEBM) and the Sociedad Espanola de Hematologia y Hemoterapia (SEHH), October 2013). With the new specifications, 170 comparisons (56%) fitted the requirements and 136 (44%) required additional review. Taking into account the number of points that exceeded the requirement, random errors, range of results in which discrepancies were detected, and range of clinical decision, it was shown that the 44% that required review were acceptable, and the 32 tests were comparable in all laboratories and analysers. CONCLUSIONS: The analysis of the results showed that the consensus requirements of the 4 scientific societies were met. However, each laboratory should aim to meet stricter criteria for total error. PMID- 26546168 TI - [Validation of an in-house method for the determination of zinc in serum: Meeting the requirements of ISO 17025]. AB - OBJECTIVE: The aim of this report is to propose a scheme for validation of an analytical technique according to ISO 17025. MATERIAL AND METHODS: According to ISO 17025, the fundamental parameters tested were: selectivity, calibration model, precision, accuracy, uncertainty of measurement, and analytical interference. RESULTS: A protocol has been developed that has been applied successfully to quantify zinc in serum by atomic absorption spectrometry. CONCLUSION: It is demonstrated that our method is selective, linear, accurate, and precise, making it suitable for use in routine diagnostics. PMID- 26546169 TI - [Impact of Lean methodology to improve care processes and levels of satisfaction in patient care in a clinical laboratory]. AB - INTRODUCTION: The application of the Lean methodology in health institutions is an effective tool to improve the capacity and workflow, as well as to increase the level of satisfaction of patients and employees. OBJECTIVE: To optimise the time of outpatient care in a clinical laboratory, by implementing a methodology based on the organisation of operational procedures to improve user satisfaction and reduce the number of complaints for delays in care. MATERIAL AND METHODS: A quasi-experimental before and after study was conducted between October 2011 to September 2012. XBar and S charts were used to observe the mean service times and standard deviation. The user satisfaction was assessed using service questionnaires. RESULTS: A reduction of 17 minutes was observed in the time of patient care from arrival to leaving the laboratory, and a decrease of 60% in complaints of delay in care. Despite the high staff turnover and 38% increase in the number of patients seen, a culture of empowerment and continuous improvement was acquired, as well as greater efficiency and productivity in the care process, which was reflected by maintaining standards 12 months after implementation. CONCLUSION: Lean is a viable methodology for clinical laboratory procedures, improving their efficiency and effectiveness. PMID- 26546170 TI - [Influence of an observer in the haemolysis produced during the extraction of blood samples in primary care]. AB - OBJECTIVE: To check whether an intervention based on direct observation and complementary information to nurses helps reduce haemolysis when drawing blood specimens. MATERIAL AND METHODS: Random sampling study in primary care centres in the serrania de Malaga health management area, using a cross-sectional, longitudinal pre- and post-intervention design. The study period was from August 2012 to January 2015. The level of free haemoglobin was measured by direct spectrophotometry in the specimens extracted. It was then checked whether the intervention influenced the level of haemolysis, and if this was maintained over time. RESULTS: The mean haemolysis measured pre-intervention was 17%, and after intervention it was 6.1%. A year later and under the same conditions, the frequency of haemolysis was measured again the samples analysed, and the percentage was 9% These results are low when compared to the level obtained pre intervention, but are higher when compared to the levels obtained immediately after the intervention. The transport and analysis conditions were the same. CONCLUSIONS: An intervention based on a direct and informative observation in the process of collecting blood samples contributes significantly to reduce the level of haemolysis. This effect is maintained in time. This intervention needs to be repeated to maintain its effectiveness. Audits and continuing education programs are useful for quality assurance procedures, and maintain the level of care needed for a good quality of care. PMID- 26546171 TI - Does percutaneous dilatational tracheostomy increase the incidence of sternal wound infection - a single center retrospective of 4100 cases. AB - BACKGROUND: The impact of percutaneous dilatational tracheostomy (PDT) on the development of post-median sternotomy wound infection (SWI) and mediastinitis is still controversial. We aimed to investigate the frequency of cross-infection and incidence of SWI after PDT. METHODS: In a retrospective design, out of a total of 4100 procedures, all patients who had undergone median sternotomy and postoperative PDT were included from January 2010 to May 2013. For comparison of the pathogens isolated from SWIs, data from all patients who developed an SWI without a PDT during the aforementioned period were also analyzed. Demographical, pre-, peri- and post-operative data were compared. Microbiologic analysis from cultures of sternal and tracheal wounds was performed. Day and duration of tracheostomy were correlated to SWI occurrence. RESULTS: Of the 265 patients who underwent a PDT, 25 (9.4 %) developed an SWI. In this cohort, identical pathogens were isolated from the tracheostomy and SWI in 36 % (9/25) of the patients. Of the pathogens isolated from the SWIs from the PDT + SWI group, 60 % were gram positive bacteria, 20 % gram-negative bacteria and 20 % Candida spp. In the cross infection group, the patients developed the following types of SWIs: 11.1 % CDC I, 55.6 % CDC II and 33.3 % mediastinitis (CDC III). The incidence of SWI in the group SWI + PDT was 9.4 % (9.4 % vs. 3.4 %, PDT + SWI and SWI w/oPDT , respectively, p = 0.0001). In group SWI w/oPDT , only 1.5 % (2/131 vs. 5/25; p = 0.001) Candida spp were isolated from SWI. The infection-related in-hospital mortality was high in groups PDT + SWI vs. SWI w/oPDT (20 % vs. 0 %, respectively; p = 0.0001). The statistical analysis did not demonstrate any correlation between time of performing PDT and occurrence of SWI. CONCLUSIONS: There was a high incidence of microbial cross-infection from the PDTs to the sternal wounds in our study. We did not detect any correlation between the time of performing PDT and occurrence of SWI. According to our data, PDT seems to increase the incidence of SWI, especially caused by Candida spp., after cardiac surgery, which results in a prolonged hospital stay. Therefore, early antifungal prophylaxis after a PDT might be reasonable in high-risk patients on long-term mechanical ventilation if there is an impending SWI. PMID- 26546172 TI - Physicians' use of pain scale and treatment procedures among children and youth in emergency primary care - a cross sectional study. AB - BACKGROUND: Pain is a common symptom in children and youth attending casualty centres and emergency departments. The aim of this study was to acquire more knowledge about how pain in children is measured and handled by emergency primary care physicians. METHODS: A structured questionnaire study was performed among 75 emergency primary care physicians in a Norwegian accident and emergency department (AED). We used descriptive statistics to analyse the use of a pain scale, the use of weight and age when dosing pain medication, the need for more knowledge and the need for pain management procedures in children. The Pearson chi-square test was used to analyse differences between groups. RESULTS: A pain scale with a visual analogue scale (VAS) had been used by 59 % of physicians in young patients aged 9 to 19 years, by 23 % in children aged 3 to 8 years, and by 3 % in children below 3 years. A total of 63 % of physicians reported that they used the child's weight instead of the age interval when estimating the needed dose of painkillers. They relied on parents' weight estimation and seldom measured the child's weight at attendance. Most emergency medical care physicians reported a need for more knowledge and better procedures related to both pain evaluation and pain treatment in children and youth. The physicians included in the study were demographically representative of AED physicians in Norway (average age 37 years old, 55 % men, 76 % had studied medicine in Norway and 49 % had fewer than 5 years of medical experience). CONCLUSIONS: Emergency primary care physicians report a need for pain assessment procedures in children and youth. They sometimes use a pain scale when measuring and managing pain in patients aged 9 to 19 years, but seldom in younger patients. PMID- 26546173 TI - [Neglecting continuity means "laught now and cry later"]. PMID- 26546174 TI - [Nocturnal enuresis in children from 5 to 10 years of a personalized health care unit of Portugal's north zone]. PMID- 26546175 TI - Chronic hepatitis C: Burden of disease and cost associated with hospitalisations in France in 2012 (The HEPC-LONE study). AB - BACKGROUND AND OBJECTIVE: This retrospective hospital database analysis aimed to determine the burden and cost of hospitalisations related to chronic hepatitis C (CHC) infections in France in 2012. METHODS: All hospital stays with CHC (ICD-10 code B18.2) coded as the principal, related or significantly associated diagnosis were extracted from the French National Hospital database 2012 (PMSI). Hospitalisations not directly related to CHC were excluded. Patients were assigned to a liver disease stage, namely non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma or post liver transplantation. Costing was performed using French national tariffs and expressed in 2013 Euros. We documented 22,056 hospital stays involving 12,040 patients who were considered to be directly related to CHC. Of these stays, 11,779 (53.4%) were documented in patients with severe complications (decompensated cirrhosis, hepatocellular carcinoma or liver transplantation). RESULTS AND CONCLUSIONS: The mean number and duration of hospital stays increased with disease severity. Overall, 1181 patients (9.8%) died during hospitalisation. The total cost of hospital stays for CHC was estimated to be ? 61 million, of which 26.4% were attributable to hepatocellular carcinoma, 32.5% to post-liver transplantation and 21.0% to decompensated cirrhosis. Compared with a previous analysis in 2009, the number of patients hospitalised fell by 22%, although the patients hospitalised were overall more severely ill. The total cost of hospitalisation decreased by 8%, with a notably marked reduction in the number of biopsies performed (32%). This study illustrates the persistently high burden of CHC infections in France. PMID- 26546176 TI - Association of IL-17A and IL-17F gene polymorphisms with chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: A case-control study. AB - BACKGROUND: Interleukin (IL)-17 has been shown to play an important role in tissue inflammation and in the pathogenesis of immune-related liver damage. Genetic variations in IL-17 gene may be associated with the development of hepatitis B virus (HBV) infection. However, literature is scanty regarding their association. METHODS: We conducted a case-control study including 433 subjects (171 healthy controls, 130 patients with chronic hepatitis B [CHB]; and 132 patients with HBV-related liver cirrhosis [HBV-LC] to assess the association between IL-17A rs4711998, IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk of CHB and HBV-LC. Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and DNA sequencing. RESULTS: Our results revealed a statistically significant association between IL-17A rs4711998 G allele and increased risk of HBV-LC risk (OR=1.541, 95% CI 1.057-2.246, P=0.025). Subjects carrying the IL-17A rs4711998 AG genotype were 1.75 times more likely to develop HBV-LC (OR=1.757, 95% CI 1.096-2.817, P=0.026). Stratification analysis indicated that IL-17A rs4711998 G allele and AG genotype enhanced the risk of HBV LC development among men and older age (>=50years) subject groups. In addition, we found that GCT haplotype also might be a risk factor for HBV-LC (OR=2.448, 95% CI 1.137-5.271, P=0.019). Furthermore, no significant association between IL-17A rs2275913 and IL-17F rs763780 polymorphisms and CHB, HBV-LC risk was observed (P>0.05). CONCLUSION: Our data provide the first evidence that the IL-17A rs4711998 genetic variant may contribute to HBV-LC susceptibility in a Chinese population. PMID- 26546177 TI - Hepatic epithelioid hemangioendothelioma. PMID- 26546178 TI - Use of Digital Whole Slide Imaging in Dermatopathology. AB - Digital whole slide imaging (WSI) is an emerging technology for pathology interpretation, with specific challenges for dermatopathology, yet little is known about pathologists' practice patterns or perceptions regarding WSI for interpretation of melanocytic lesions. A national sample of pathologists (N = 207) was recruited from 864 invited pathologists from ten US states (CA, CT, HI, IA, KY, LA, NJ, NM, UT, and WA). Pathologists who had interpreted melanocytic lesions in the past year were surveyed in this cross-sectional study. The survey included questions on pathologists' experience, WSI practice patterns and perceptions using a 6-point Likert scale. Agreement was summarized with descriptive statistics to characterize pathologists' use and perceptions of WSI. The majority of participating pathologists were between 40 and 59 years of age (62%) and not affiliated with an academic medical center (71%). Use of WSI was seen more often among dermatopathologists and participants affiliated with an academic medical center. Experience with WSI was reported by 41%, with the most common type of use being for education and testing (CME, board exams, and teaching in general, 71%), and clinical use at tumor boards and conferences (44%). Most respondents (77%) agreed that accurate diagnoses can be made with this technology, and 59% agreed that benefits of WSI outweigh concerns. However, 78% of pathologists reported that digital slides are too slow for routine clinical interpretation. The respondents were equally split as to whether they would like to adopt WSI (49%) or not (51%). The majority of pathologists who interpret melanocytic lesions do not use WSI, but among pathologists who do, use is largely for CME, licensure/board exams, and teaching. Positive perceptions regarding WSI slightly outweigh negative perceptions. Understanding practice patterns with WSI as dissemination advances may facilitate concordance of perceptions with adoption of the technology. PMID- 26546179 TI - Sequential Registration-Based Segmentation of the Prostate Gland in MR Image Volumes. AB - Accurate and fast segmentation and volume estimation of the prostate gland in magnetic resonance (MR) images are necessary steps in the diagnosis, treatment, and monitoring of prostate cancer. This paper presents an algorithm for the prostate gland volume estimation based on the semi-automated segmentation of individual slices in T2-weighted MR image sequences. The proposed sequential registration-based segmentation (SRS) algorithm, which was inspired by the clinical workflow during medical image contouring, relies on inter-slice image registration and user interaction/correction to segment the prostate gland without the use of an anatomical atlas. It automatically generates contours for each slice using a registration algorithm, provided that the user edits and approves the marking in some previous slices. We conducted comprehensive experiments to measure the performance of the proposed algorithm using three registration methods (i.e., rigid, affine, and nonrigid). Five radiation oncologists participated in the study where they contoured the prostate MR (T2 weighted) images of 15 patients both manually and using the SRS algorithm. Compared to the manual segmentation, on average, the SRS algorithm reduced the contouring time by 62% (a speedup factor of 2.64*) while maintaining the segmentation accuracy at the same level as the intra-user agreement level (i.e., Dice similarity coefficient of 91 versus 90%). The proposed algorithm exploits the inter-slice similarity of volumetric MR image series to achieve highly accurate results while significantly reducing the contouring time. PMID- 26546180 TI - Analysis of Risk Factors for Intraoperative Conversion of Laparoscopic Myomectomy. AB - OBJECTIVES: To report the surgical outcomes of laparoscopic myomectomy (LM) and abdominal myomectomy (AM) at a high-volume tertiary care hospital, to evaluate the risk of conversion during LM, and to analyze the associated risk factors. DESIGN: Retrospective cohort study (Canadian Task Force classification II). PATIENTS: All patients who underwent LM and AM in a tertiary academic center in Boston, Massachusetts between 2009 and 2012. INTERVENTION: Medical records were reviewed for baseline characteristics and perioperative outcomes. Robot-assisted laparoscopy was considered a subtype of LM. RESULTS: A total of 966 patients underwent myomectomy during the study period, including 731 LM cases (75.67%) and 235 AM cases (24.33%). Compared with patients undergoing LM, those undergoing AM had more myomas removed and heavier specimens (mean number of myomas, 12.60 vs 3.54, p <= .001; mean weight, 592.75 g vs 263.4 g, p <= .001). Conversion was necessary in 8 LM cases (1.09%). All conversions were reactive in nature and were associated with greater blood loss (mean, 1381.25 vs 167.95 mL; p <= .001) and longer hospital stay (mean, 3.13 vs 0.55 days; p <= .001) compared with cases without conversion. Factors associated with conversion included both the number and the weight of myomas removed (mean number, 9.75 vs 3.48, p = .003; mean weight, 667.9 vs 259.25 g, p = .015), especially with myomas weighing >500 g (odds ratio = 8.551; p = .005). CONCLUSION: The risk of conversion for LM was low (1.09%) in this cohort, and was associated both with the number and the weight of myomas removed. LM is a feasible approach for surgical management of myomas in the majority of cases; however, when myomas are expected to weigh >500 g, it may be prudent to consider referring those cases to specialized centers with highly experienced teams. PMID- 26546181 TI - Comparison of Two Techniques of Laparoscopy-Assisted Peritoneal Vaginoplasty. AB - Neovagina creation is essential for patients with the Mayer-Rokitansky-Kuster Hauser syndrome. We compared a technique involved the pushing down of the peritoneum with the technique of separating the peritoneum for laparoscopy assisted peritoneal vaginoplasty. We collected patients with congenital absence of vagina who underwent laparoscopy-assisted peritoneal vaginoplasty of the First Affiliated Hospital of Zhengzhou University between January 2011 and May 2013. The 2 surgical groups (pushing group and separating group) were compared for various parameters. The values of the following parameters were significantly lower for the pushing group compared with the separating group: mean operating time (78 +/- 13 minutes vs 135 +/- 28 minutes), mean duration of hospitalization (12.9 +/- 2.7 days vs 18.0 +/- 3.8 days), mean cost of hospitalization (14 016 +/ 1640 RMB vs 18 783 +/- 2143 RMB), requirement for a drainage tube (4% vs 27%; chi(2) = 8.864), requirement for analgesic drugs (20% vs 40%; chi(2) = 3.977), and postoperative rehospitalization (3.3% vs 10.0% at 2 months and 6.7% vs 26.7% at 6 months; chi(2) = 4.268 and 5.196). Mean values for blood loss (57 +/- 19 mL vs 66 +/- 20 mL), time to pass gas (21 +/- 4 hours vs 23 +/- 7 hours), and length of the reconstructed vagina (9.0 +/- 0.4 cm vs 8.9 +/- 0.5 cm) were not significantly different between the 2 groups. In addition, mean postoperative Female Sexual Function Index score did not differ significantly between the 2 groups or among the 2 groups and a control group (27.0 +/- 4.8 vs 26.7 +/- 5.2 vs 27.9 +/- 4.5; p > .05). The technique involving pushing down of the peritoneum offers advantages of reduced cost, complications, hospitalization, operative time, and pain over the traditional technique. Sexuality approaches so-called "normal" sexuality. PMID- 26546182 TI - Transduodenal Ampullectomy for the Treatment of Early-Stage Ampulla of Vater Cancer. AB - BACKGROUND: Transduodenal ampullectomy (TDA) is a less invasive procedure than pancreaticoduodenectomy (PD). However, the outcomes of TDA and PD have been compared rarely in early ampullary cancer. METHODS: From September 1994 to June 2013, the patients who underwent curative surgery for Tis or T1 ampulla of Vater neoplasm were identified. The patients were divided into two groups according to the types of surgery; TDA group and PD group. The patient characteristics and survival outcomes were retrospectively investigated between the two groups. RESULTS: Total 137 patients were included in this study. The 18 patients underwent TDA and 119 patients underwent PD for Tis or T1 ampullary cancer. There was no lymph node metastasis in the patients with Tis tumor although 10 of 104 patients had lymph node metastasis in T1 cancer. After a median follow-up of 50 months (range, 6-148), there were no recurrence after TDA for Tis tumor. However, the TDA was associated with higher local recurrence rate than PD in the patients with T1 ampullary cancer on Kaplan-Meier survival analysis (p = 0.007). CONCLUSION: The TDA is feasible treatment for Tis ampulla of Vater neoplasm. However, TDA is unsuitable for the treatment of T1 ampulla of Vater cancer. PMID- 26546183 TI - Upregulation of Neutrophil Gelatinase-Associated Lipocalin in Colorectal Cancer Predicts Poor Patient Survival: Reply. PMID- 26546185 TI - The Role of International Volunteers in the Growth of Surgical Capacity in Post earthquake Haiti. AB - BACKGROUND: The 2010 Haiti earthquake severely strained local healthcare infrastructure. In the wake of this healthcare crisis, international organizations provided volunteer support. Studies demonstrate that this support improved short-term recovery; however, it is unclear how long-term surgical capacity has changed and what role volunteer surgical relief efforts have played. Our goal was to investigate the role of international surgical volunteers in the increase of surgical capacity following the 2010 Haiti earthquake. METHODS: We retrospectively analyzed the operative reports of 3208 patients at a general, trauma and critical care hospital in Port-au-Prince from June 2010 through December 2013. We collected data on patient demographics and operation subspecialty. Surgeons and anesthesiologists were categorized by subspecialty training and as local healthcare providers or international volunteers. We performed analysis of variance to detect changes in surgical capacity over time and to estimate the role volunteers play in these changes. RESULTS: Overall number of monthly operations increased over the 2.5 years post-earthquake. The percentage of orthopedic operations declined while the percentage of other subspecialty operations increased (p = 0.0003). The percentage of operations performed by international volunteer surgeons did not change (p = 0.51); however, the percentage of operations staffed by volunteer anesthesiologists declined (p = 0.058). The percentage of operations performed by matching specialty- and subspecialty-trained international volunteers has not changed (p = 0.54). CONCLUSIONS: Haitian post-earthquake local and overall surgical capacity has steadily increased, particularly for provision of subspecialty operations. Surgical volunteers have played a consistent role in the recovery of surgical capacity. An increased focus on access to surgical services and resource allocation for long-term surgical efforts particularly in the realm of subspecialty surgery may lead to full recovery of surgical capacity after a large and devastating natural disaster. PMID- 26546184 TI - Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival. AB - BACKGROUND: The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival. METHODS: Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed. RESULTS: A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8%). A postoperative complication occurred in 99 patients for a morbidity of 37.4%; five patients (1.9%) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95% CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95% CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95% CI 2.24-13.80; P < 0.001). CONCLUSION: Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective. PMID- 26546186 TI - Associations with Perioperative Mortality Rate at a Major Referral Hospital in Rwanda. AB - BACKGROUND: Little is known about perioperative mortality in sub-Saharan Africa. The perioperative mortality rate (POMR) and associated factors at a major referral hospital in Rwanda were measured. METHODS: The operative activity at University Teaching Hospital of Kigali was evaluated through an operative database. As a part of this larger study, patient characteristics and outcomes were measured to determine areas for improvement in patient care. Data were collected on patient demographics, surgeon, diagnosis, and operation over a 12 month period. The primary outcome was POMR. Secondary outcomes were timing and hospital location of death. RESULTS: The POMR was 6 %. POMR in patients under 5 years of age was 10 %, 3 % in patients 5-14 years and 6 % in patients age >14 years. For emergency and elective operations, POMR was 9 and 2 %, respectively. POMR was associated with emergency status, congenital anomalies, repeat operations, referral outside Kigali, and female gender. Orthopedic procedures and age 5-14 years were associated with decreased odds of mortality. Forty-nine percent of deaths occurred in the post-operative recovery room and 35 % of deaths occurred within the first post-operative day. CONCLUSIONS: The POMR at a large referral hospital in Rwanda is <10 % demonstrating that surgery can save lives even in resource-limited settings. Emergency operations are associated with higher mortality, which could potentially be improved with faster identification and transfer from district hospitals. Nearly half of deaths occurred in the post operative recovery room. Multidisciplinary audits of operative mortalities could help guide improvements in surgical care. PMID- 26546187 TI - Self-Gripping Meshes for Lichtenstein Repair. Do We Need Additional Suture Fixation? AB - BACKGROUND: The Lichtenstein repair is a frequently used treatment of inguinal hernias. In recent years, there has been an increasing tendency to apply self gripping meshes (s.g). In many cases, additional suture of the mesh is carried out; however, it is uncertain what the benefits or potential risks of this actually are. METHODS: The evaluation was undertaken on the basis of the Herniamed register, and covered all unilateral Lichtenstein operations between 01.09.2009 up to 30.09.2013. The analysis only included patients with whom s.g. meshes with resorbable micro hooks had been used (Progrip((r)), Covidien) and who had undergone a full 1-year follow-up examination (80.15 %). RESULTS: In total, 2095 patients were suitable for analysis, of which 816 (38.95 %) cases received an additional suture fixation (Fix). With increasing hernia size, more frequent fixation took place (29.97 % of hernias <1.5 cm vs. 46.65 % of hernias >3 cm, p < 0.001). The recurrence rates 1 year after surgery did not show any significant differences (Fix. 0.86 % vs. No Fix. 1.17 %; p = 0.661) with and without fixation, even when being adjusted for covariables. Likewise, no differences were noted in terms of postoperative complications (Fix. 5.15 % vs. No Fix. 5.08 %; p = 1.0). In addition, the numbers of patients needing to be treated after 1 year for chronic pain were also comparable (Fix. 2.33 % vs. No Fix. 2.97 %; p = 0.411). CONCLUSION: Within the group that did not have additional suture fixation of self-gripping meshes (No Fix.), the length of operations was on average 8 min shorter (p < 0.001). No differences could be observed in terms of postoperative complications, treatment requiring chronic pain and recurrence rates. PMID- 26546188 TI - Hepatic Artery Reconstruction with a Continuous Suture Method for Hepato-Biliary Pancreatic Surgery. AB - BACKGROUND: In some cases, hepato-biliary-pancreatic (HBP) surgery requires hepatic artery resection and hepatic artery reconstruction (HAR) for histologically curative resection. We describe our surgical HAR technique, which involves continuous suturing, and we report the results of a study of the surgical outcomes. METHODS: Between 2000 and 2014, 380 patients underwent radical surgery for advanced HBP malignancies (118 bile duct cancers, 189 pancreatic head cancers, and 73 gallbladder cancers), 24 of whom (6.3 %) underwent HAR (for complete cure of 16 bile duct cancers, 5 pancreatic cancers, and 3 gallbladder cancers). The 24 surgical procedures included 8 hepato-pancreatoduodenectomies, 10 hepatectomies, and 6 pancreatoduodenectomies. The ends of the 2 arteries were spatulated, and the reconstruction was performed with a continuous 7-0 polypropylene suture under loupe magnification. RESULTS: Eighteen right hepatic arteries, 4 left hepatic arteries, and 2 proper hepatic arteries were resected and reconstructed. Median HAR time was 18 min (range 9-31 min). End-to-end anastomosis was performed in 7 patients, and heterogeneous reconstruction was performed in 17 patients (with 9 colic arteries, 4 gastroduodenal arteries, and 4 others). Doppler ultrasonography performed upon vessel reconstruction depicted pulsatile flow within the intrahepatic arteries in all cases, and patency of the reconstructed vessel was confirmed postoperatively by contrast-enhanced CT in 19 patients (82.6 %). Morbidity occurred in 10 patients (42 %), including 4 HAR related complications: 3 bile leakages and 1 hepatic abscess. CONCLUSION: Our HAR method can be performed safely and easily by general surgeons. It may be a time saving procedure that yields acceptable patency and morbidity rates. PMID- 26546189 TI - Characteristics of Persistent Hyperparathyroidism After Renal Transplantation. AB - BACKGROUND: Persistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood. METHODS: A retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1 year after PTx) laboratory results were analyzed for PTx efficacy. RESULTS: Data for 520 patients were analyzed. On multivariate analysis, long dialysis duration (p = 0.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (p = 0.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (p = 0.041, HR 1.01), post-RTx (<2 weeks) high calcium (Ca) (p < 0.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (p = 0.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference. CONCLUSIONS: Several risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT. PMID- 26546190 TI - Partial Thyroidectomy for Papillary Thyroid Microcarcinoma: Is Completion Total Thyroidectomy Indicated? AB - BACKGROUND: Total thyroidectomy is a well-established surgical approach for the management of papillary thyroid cancer (PTC). However, the best surgical approach for papillary microcarcinoma is nowadays still debated. Both total thyroidectomy and simple lobectomy are used. We report the experience of a single University center in the treatment of thyroid microcarcinoma. METHODS: A retrospective analysis on all patients who underwent thyroid surgery at our institution over a 24-year period (1991-2015) was performed. Patients were grouped according to whether they received total thyroidectomy (Group 1) or lobectomy (Group 2). Follow-up was made by routine clinical and ultrasound examination. Specific outcomes such as recurrence and need for reoperation as well as complications (transient vocal cord paralysis and hypocalcemia) were analyzed. RESULTS: During the study period 880 patients underwent surgery for PTC. Group 1 and 2 consisted, respectively, of 756 and 124 patients. A micro PTC (<10 mm) was present in 251 and 69 specimen of Group 1 and 2. No evidence of disease recurrence in the follow up was reported in patients with microPTC in Group 1 and in 57 patients of Group 2. In the remaining 12 patients completion thyroidectomy was carried out due to ultrasound findings of contralateral nodules (10), lymphadenopathy (1), and capsular invasion (1). Five of these patients had a contralateral papillary carcinoma on final histopathologic examination. Thus recurrence rate for patients of Group 2 was 7.3%. Morbidity rates were, respectively, for Group 1 and 2: transient nerve palsy 81 and 5 (11 vs. 7.3%, p = ns), transient hypoparathyroidism (Calcium <2.00 mmol/L) 137 (18.6%) and 0 (p < 0.0001). Three of the 12 patients of Group 2 undergoing further surgery had a transient hypoparathyroidism. CONCLUSIONS: Thyroid lobectomy is an effective surgical strategy to manage papillary microcarcinomas with low complications. Routine completion thyroidectomy is not mandatory. Appropriate selection excluding high risk patients is of paramount importance in order to achieve the best results. PMID- 26546191 TI - Quality of Life in Thyroid Cancer is Similar to That of Other Cancers with Worse Survival. AB - BACKGROUND: The incidence of thyroid cancer is increasing. As such, the number of survivors is rising, and it has been shown that their quality of life (QOL) is worse than expected. Using results from the North American Thyroid Cancer Survivorship Study (NATCSS), a large-scale survivorship study, we aim to compare the QOL of thyroid cancer survivors to the QOL of survivors of other types of cancer. METHODS: The NATCSS assessed QOL overall and in four subcategories: physical, psychological, social, and spiritual well-being using the QOL-Cancer Survivor (QOL-CS) instrument. Studies that used the QOL-CS to evaluate survivors of other types of cancers were compared to the NATCSS findings using two-tailed t tests. RESULTS: We compared results from NATCSS to QOL survivorship studies in colon, glioma, breast, and gynecologic cancer. The mean overall QOL in NATCSS was 5.56 (on a scale of 0-10, where 10 is the best). Overall QOL of patients with thyroid cancer was similar to that of patients with colon cancer (mean 5.20, p = 0.13), glioma (mean 5.96, p = 0.23), and gynecologic cancer (mean 5.59, p = 0.43). It was worse than patients surveyed with breast cancer (mean 6.51, p < 0.01). CONCLUSIONS: We found the self-reported QOL of thyroid cancer survivors in our study population is overall similar to or worse than that of survivors of other types of cancer surveyed with the same instrument. This should heighten awareness of the significance of a thyroid cancer diagnosis and highlights the need for further research in how to improve care for this enlarging group of patients. PMID- 26546192 TI - Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease. AB - BACKGROUND: To reduce intraoperative and postoperative complications, using Lugol solution to preoperatively prepare patients with Graves' disease has (1) rapidly reduced the severity of thyrotoxicosis and (2) reduced the vascularity of the thyroid gland. The vascularity reduction normally accompanies reducing the severity of thyrotoxicosis. However, the effects and mechanism of Lugol solution for reducing blood flow have not been well investigated in the patients with euthyroid (normally functioning thyroid) Graves' disease. METHODS: Twenty-five patients with euthyroid Graves' disease being preoperatively treated with Lugol solution for 10 days were measured, at baseline and on the operative day, for (1) superior thyroid artery blood flow; (2) systemic angiogenic factor (VEGF); and (3) systemic inflammatory factor [interleukin (IL)-16]. RESULTS: All three parameters were significantly (p < 0.0001) lower after 10 days of Lugol solution treatment. The average reductions were blood flow: 60% (0.294 vs. 0.117 L/min), serum VEGF: 55% (169.8 vs. 76.7 pg/mL), and serum IL-16: 50% (427.2 vs. 214.2; pg/mL). CONCLUSION: Lugol solution significantly reduced thyroid arterial blood flow, VEGF, and IL-16, even in patients with euthyroid Graves' disease. We recommend routine preoperative Lugol solution treatment for all patients with Graves' disease. PMID- 26546193 TI - Transoral Endoscopic Thyroidectomy Vestibular Approach: A Series of the First 60 Human Cases. AB - BACKGROUND: Natural orifice transluminal endoscopic surgery has been adopted for thyroid surgery because of its potential for scar-free operation. However, the previous technique still has some limitations. Thus, we present our initial experience in transoral endoscopic thyroidectomy vestibular approach (TOETVA). METHODS: From April 2014 to January 2015, we used a three-port technique through the oral vestibule, one 10-mm port for laparoscope and two additional 5-mm ports for instruments. The CO2 insufflation pressure was set at 6 mm Hg. An anterior cervical subplatysmal space was created from the oral vestibule down to the sternal notch. The thyroidectomy was done endoscopically using conventional laparoscopic instruments and an ultrasonic device. RESULTS: A series of 60 procedures were accomplished successfully. 42 patients had single-thyroid nodules, and a lobectomy was performed. 22 patients had multinodular goiters and two patients had Graves' disease, with total thyroidectomy or Hartley-Dunhill procedures performed. Two had papillary thyroid carcinoma, and total thyroidectomy with central node dissection was performed. The median operative time was 115.5 min (range 75-300 min). The median blood loss was 30 mL (range 8 130 mL). Two patients experienced a transient hoarseness, which was resolved within 2 months. One patient experienced a late postoperative hematoma, which was treated conservatively. No mental nerve injury or infections were found. The patients were discharged in an average of 3.6 days (range 2-7 days) postoperatively. CONCLUSION: TOETVA is safe and feasible, resulting in no visible scarring. This technique may provide a method for ideal cosmetic results. PMID- 26546194 TI - Prospective Evaluation of Innovative Force Assessing Firmware in Simulation to Improve the Technical Competence of Surgical Trainees. AB - INTRODUCTION: Suturing is an integral part of all surgeries. In minimal access surgery, the force exerted is based only on visual perception (tautness of the thread and degree of tissue deformation). An unbalanced suture force can cause tissue rupture or cut-through resulting in avoidable morbidity and mortality. There is a need to find ways of improving surgical dexterity and finesse without adversely affecting patient outcomes. AIM: We aimed to calculate the knot-tying force in minimal access pancreatic surgery (MAPS) performed by experienced surgeons (ES) and use this information to develop a surgical suturing model to train the surgical trainees. We have developed a firmware for force sensor calibration and post-data analysis, using which we aimed to compare the differences in forces applied by a trainee as compared to ES. RESULTS: Our technology showed that, as compared to the ES, the trainee's (TS) knot was unbalanced with significant differences in force applied per knot for each of the knots (P < 0.01). The shape of the Force curve for each suture was also different for the TS as compared to the ES. After using the training tool, the forces applied by the TS and the Force curve for the whole suture were similar to those of the ES. CONCLUSION: Our firmware promises to be an excellent training tool for organ anastomosis. Considering the complexity and likely complications of MAPS, it is a sine qua non that the surgeon be highly experienced and skilled. Surgical simulation is attractive because it avoids the use of patients for skills practice and provides relevant technical training for trainees before they can safely operate on humans. PMID- 26546195 TI - Are stem cells the next frontier for hypoplastic left heart syndrome? What are the promise, the reality, and the future? PMID- 26546196 TI - Readmissions and the law of unintended consequences. PMID- 26546197 TI - Stem cell therapy for heart failure: Out with the new and in with the old? PMID- 26546198 TI - Barlow disease: Simple and complex. PMID- 26546199 TI - The influence of percutaneous mitral repair programs on mitral surgery volume: What should we expect and what can we do? PMID- 26546200 TI - Preimplantation valvuloplasty in transcatheter aortic valve replacement: To BAV or not to BAV? PMID- 26546201 TI - Valve-sparing root replacement for failed pulmonary autografts: Should a David repair a Ross? PMID- 26546202 TI - Caution: There is no "all or none" with Ebstein anomaly. PMID- 26546203 TI - The devil is in the details: Managing chest drains and interpreting negative randomized trial data. PMID- 26546204 TI - Building a better bridge: Remodeling, recovery, and a better understanding of the biologic foundation of mechanical circulatory support. PMID- 26546206 TI - Elastin deficiency in Williams syndrome may explain postoperative major adverse cardiac events. PMID- 26546205 TI - Combining clinical databases with genetic studies to help advance the causation model of congenital heart disease. PMID- 26546207 TI - A new lung-marking technique for robotic cases. PMID- 26546208 TI - Main objectives of preoperative marking technique for hardly palpable lung nodules. PMID- 26546209 TI - Sarcoptic mange breaks up bottom-up regulation of body condition in a large herbivore population. AB - BACKGROUND: Both parasitic load and resource availability can impact individual fitness, yet little is known about the interplay between these parameters in shaping body condition, a key determinant of fitness in wild mammals inhabiting seasonal environments. METHODS: Using partial least square regressions (PLSR), we explored how temporal variation in climatic conditions, vegetation dynamics and sarcoptic mange (Sarcoptes scabiei) severity impacted body condition of 473 Iberian ibexes (Capra pyrenaica) harvested between 1995 and 2008 in the highly seasonal Alpine ecosystem of Sierra Nevada Natural Space (SNNS), southern Spain. RESULTS: Bottom-up regulation was found to only occur in healthy ibexes; the condition of infected ibexes was independent of primary productivity and snow cover. No link between ibex abundance and ibex body condition could be established when only considering infected individuals. CONCLUSIONS: The pernicious effects of mange on Iberian ibexes overcome the benefits of favorable environmental conditions. Even though the increase in primary production exerts a positive effect on the body condition of healthy ibexes, the scabietic individuals do not derive any advantage from increased resource availability. Further applied research coupled with continuous sanitary surveillance are needed to address remaining knowledge gaps associated with the transmission dynamics and management of sarcoptic mange in free-living populations. PMID- 26546210 TI - [Use of a homemade introducer guide (bougie) for intubation in emergency situation in patients who present with difficult airway: a case series]. AB - BACKGROUND AND OBJECTIVES: The incidence of difficult airway reaches 10% of emergency intubations. Although few studies address the use of handmade introducer guides in emergency and intensive care environment, there are descriptions of handmade guides available on the Internet. We describe a case series on the use of a handmade introducer guide (bougie) for emergency intubation in patients with difficult airway. CASE REPORT: The handmade introducer guide was used in five consecutive patients with difficult airways, and clinical instability and in the absence of another immediate method to obtain an airway. This technique provided successful intubation and there were no complications. CONCLUSIONS: The use of the handmade introducer guide can be a useful option for the management of difficult airways. PMID- 26546211 TI - [Accidental catheterization of epidural venous plexus: tomographic analysis]. AB - BACKGROUND AND OBJECTIVES: Inadvertent venous catheterizations occur in approximately 9% of lumbar epidural anesthetic procedures with catheter placement and, if not promptly recognized, can result in fatal consequences. The objective of this report is to describe a case of accidental catheterization of epidural venous plexus and its recording by computed tomography with contrast injection through the catheter. CASE REPORT: A female patient in her sixties, physical status II (ASA), underwent conventional cholecystectomy under balanced general anesthesia and an epidural with catheter for postoperative analgesia. During surgery, there was clinical suspicion of accidental catheterization of epidural venous plexus because of blood backflow through the catheter, confirmed by the administration of a test dose through the catheter. After the surgery, a CT scan was obtained after contrast injection through the catheter. Contrast was observed all the way from the skin to the azygos vein, passing through anterior and posterior epidural venous plexuses and intervertebral vein. CONCLUSION: It is possible to identify the actual placement of the epidural catheter, as well as to register an accidental catheterization of the epidural venous plexus, using computed tomography with contrast injection through the epidural catheter. PMID- 26546212 TI - PPL catalyzed four-component PASE synthesis of 5-monosubstituted barbiturates: Structure and pharmacological properties. AB - Enzymatic four-component reactions are very rare although three-component enzymatic promiscuous reactions are widely reported. Herein, we report an efficient PASE protocol for the synthesis of potentially lipophilic zwitterionic 5-monosubstituted barbiturates by four component reaction of mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde and barbituric acid in ethanol at room temperature. Seven different lipases were screened for their promiscuous activity towards the synthesis of 5-monosubstituted barbiturates and the lipase from porcine pancreas (PPL) found to give optimum efficiency. The zwitterionic 5 monosubstituted barbiturates with pyrazolyl ring showed promising pharmacological activity upon screening for antibacterial and apoptotic properties. PMID- 26546213 TI - 1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile. AB - We report the further optimization of our series 1H-pyrazolo[3,4-g]hexahydro isoquinoline sulfonamides as GR antagonists. By incorporating a heteroaryl ketone group at the ring junction, we have obtained compounds with excellent functional GR antagonism. Optimization of the sulfonamide substituent has provided compounds with a very desirable overall profile, including minimal hERG activity, good bioavailability and in vivo efficacy. PMID- 26546214 TI - Acylhydrazone derivatives as potential anticancer agents: Synthesis, bio evaluation and mechanism of action. AB - A series of novel acylhydrazone derivatives were designed, synthesized and evaluated for their potential cytotoxic effects against human cancer cell lines. The preliminary results indicated that some of the obtained compounds (such as 8b, 13c) exhibited good to moderate cytotoxic activities against human HepG2, Huh 7, and BCG-823 cell lines. Especially, compounds 8c and 8e presented obviously selective cytotoxic activities against Huh-7 in vitro (8c, IC50=7.74+/ 2.18MUg/mL; 8e, IC50=4.46+/-1.05MUg/mL) compared to 5-FU (IC50=10.41+/ 3.41MUg/mL). The highly potential compounds to induce apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compounds 8b and 13c were further evaluated using Annexin V-FITC/propidium iodide dual staining assay. PMID- 26546215 TI - Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides. AB - The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2 yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9MUM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew. PMID- 26546216 TI - Discovery of novel 2-benzylisoquinolin-1(2H)-ones as potent vasodilative agents. AB - 2-Benzylisoquinolin-1(2H)-ones has been proposed as vasodilative agents on the basis of scaffold hopping. In the present study, a series of 2-benzylisoquinolin 1(2H)-ones were synthesized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60mM KCl. The structure-activity relationships of target compounds were discussed. Among these compounds, C7 and C8 displayed potent vasodilative effects and significantly inhibited the contraction of rat mesenteric arterial rings induced by phenylephrine. The antihypertensive effects of compounds C7 and C8 on SHR were further evaluated. The results indicated that oral administrational C7 and C8 can significantly reduce both diastolic and systolic blood pressure in a dose dependent manner. Moreover, C7 maintained the effects for 4h at a dosage of 4.0mg/kg. These findings suggest that the title compounds can serve as novel vasodilative agents and promising antihypertensive agents. PMID- 26546217 TI - Identification and activity of inhibitors of the essential nematode-specific metalloprotease DPY-31. AB - Infection by parasitic nematodes is widespread in the developing world causing extensive morbidity and mortality. Furthermore, infection of animals is a global problem, with a substantial impact on food production. Here we identify small molecule inhibitors of a nematode-specific metalloprotease, DPY-31, using both known metalloprotease inhibitors and virtual screening. This strategy successfully identified several MUM inhibitors of DPY-31 from both the human filarial nematode Brugia malayi, and the parasitic gastrointestinal nematode of sheep Teladorsagia circumcincta. Further studies using both free living and parasitic nematodes show that these inhibitors elicit the severe body morphology defect 'Dumpy' (Dpy; shorter and fatter), a predominantly non-viable phenotype consistent with mutants lacking the DPY-31 gene. Taken together, these results represent a start point in developing DPY-31 inhibition as a totally novel mechanism for treating infection by parasitic nematodes in humans and animals. PMID- 26546218 TI - Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin. AB - A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP 4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan. PMID- 26546219 TI - Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering. AB - The propensity for cancer cells to accumulate additional centrosomes relative to normal cells could be exploited for therapeutic benefit in oncology. Following literature reports that suggested TNKS1 (tankyrase 1) and PARP16 may be involved with spindle structure and function and may play a role in suppressing multi polar spindle formation in cells with supernumerary centrosomes, we initiated a phenotypic screen to look for small molecule poly (ADP-ribose) polymerase (PARP) enzyme family inhibitors that could produce a multi-polar spindle phenotype via declustering of centrosomes. Screening of AstraZeneca's collection of phthalazinone PARP inhibitors in HeLa cells using high-content screening techniques identified several compounds that produced a multi-polar spindle phenotype at low nanomolar concentrations. Characterization of these compounds across a broad panel of PARP family enzyme assays indicated that they had activity against several PARP family enzymes, including PARP1, 2, 3, 5a, 5b, and 6. Further optimization of these initial hits for improved declustering potency, solubility, permeability, and oral bioavailability resulted in AZ0108, a PARP1, 2, 6 inhibitor that potently inhibits centrosome clustering and is suitable for in vivo efficacy and tolerability studies. PMID- 26546220 TI - Attenuation of TNF-alpha secretion by L-proline-based cyclic dipeptides produced by culture broth of Pseudomonas aeruginosa. AB - To identify small molecule inhibitors of TNF-alpha, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3) and cyclo(trans-4-hydroxy-l-Pro-l-Leu) (4). Compounds 1 and 3 exhibited potent inhibition of TNF-alpha release with IC50 values of 4.5 and 14.2MUg/mL, respectively, while EEPA showed IC50 of 38.8MUg/mL under lipopolysaccharide treated RAW 264.7 cell ELISA assay. Also, marked attenuation of mRNA-expression of TNF-alpha was shown by all compounds. In vivo testing in rats of EEPA and chemically synthesized 4 validated significant TNF-alpha reduction with 51% (500mg/kg) and 79% (50mg/kg), respectively. In addition, all compounds exhibited significant diminution of IL-1beta and IL-6 mRNA-expression levels and NO production. All samples displayed only weak toxicity to lipopolysaccharide induced RAW 264.7 cells. PMID- 26546221 TI - Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors. AB - A new series of triarylpyrazoline derivatives 8a-p containing the most important COX-2 pharmacophore (SO2CH3 or/and SO2NH2) were synthesized by reaction of propen 1-one derivatives 6a-h with different phenyl hydrazine hydrochloride derivatives 7a-b in aqueous ethanol. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and showed good in vivo anti-inflammatory activity. Compounds 8g, 8j and 8o showed the highest anti-inflammatory activity and were less ulcerogenic (Ulcer Index=6.85, 7.7, 5.92, respectively) than indomethacin (Ulcer Index=12.3) and comparable to celecoxib (Ulcer Index=4.85). PMID- 26546222 TI - Naltrexone: Not Just for Opioids Anymore. AB - Naltrexone is a semi-synthetic opioid with competitive antagonist activity at mu opioid receptors. Its efficacy has been demonstrated in the treatment of alcohol and opioid dependence, but adherence to daily dosing has been recognized as a factor limiting long-term effectiveness. Recently, a long-acting injectable formulation of naltrexone has received FDA-approval for treating alcohol and opioid dependence. This article reviews the pharmacology of naltrexone, the current evidence supporting the use of extended-release naltrexone, and the clinical challenges in the induction of patients to this medication. PMID- 26546223 TI - [Not Available]. PMID- 26546224 TI - Exposure to mobile phone electromagnetic field radiation, ringtone and vibration affects anxiety-like behaviour and oxidative stress biomarkers in albino wistar rats. AB - Research on the effects of Mobile phone radio frequency emissions on biological systems has been focused on noise and vibrations as auditory stressors. This study investigated the potential effects of exposure to mobile phone electromagnetic field radiation, ringtone and vibration on anxiety-like behaviour and oxidative stress biomarkers in albino wistar rats. Twenty five male wistar rats were randomly divided into five groups of 5 animals each: group I: exposed to mobile phone in switched off mode (control), group II: exposed to mobile phone in silent mode, group III: exposed to mobile phone in vibration mode, group IV: exposed to mobile phone in ringtone mode, group V: exposed to mobile phone in vibration and ringtone mode. The animals in group II to V were exposed to 10 min call (30 missed calls for 20 s each) per day for 4 weeks. Neurobehavioural studies for assessing anxiety were carried out 24 h after the last exposure and the animals were sacrificed. Brain samples were collected for biochemical evaluation immediately. Results obtained showed a significant decrease (P < 0.05) in open arm duration in all the experimental groups when compared to the control. A significant decrease (P < 0.05) was also observed in catalase activity in group IV and V when compared to the control. In conclusion, the results of the present study indicates that 4 weeks exposure to electromagnetic radiation, vibration, ringtone or both produced a significant effect on anxiety-like behavior and oxidative stress in young wistar rats. PMID- 26546225 TI - New insights into the interplay between codon bias determinants in plants. AB - Codon bias is the non-random use of synonymous codons, a phenomenon that has been observed in species as diverse as bacteria, plants and mammals. The preferential use of particular synonymous codons may reflect neutral mechanisms (e.g. mutational bias, G|C-biased gene conversion, genetic drift) and/or selection for mRNA stability, translational efficiency and accuracy. The extent to which these different factors influence codon usage is unknown, so we dissected the contribution of mutational bias and selection towards codon bias in genes from 15 eudicots, 4 monocots and 2 mosses. We analysed the frequency of mononucleotides, dinucleotides and trinucleotides and investigated whether the compositional genomic background could account for the observed codon usage profiles. Neutral forces such as mutational pressure and G|C-biased gene conversion appeared to underlie most of the observed codon bias, although there was also evidence for the selection of optimal translational efficiency and mRNA folding. Our data confirmed the compositional differences between monocots and dicots, with the former featuring in general a lower background compositional bias but a higher overall codon bias. PMID- 26546226 TI - Phylogeny and evolution of plant cyclic nucleotide-gated ion channel (CNGC) gene family and functional analyses of tomato CNGCs. AB - Cyclic nucleotide-gated ion channels (CNGCs) are calcium-permeable channels that are involved in various biological functions. Nevertheless, phylogeny and function of plant CNGCs are not well understood. In this study, 333 CNGC genes from 15 plant species were identified using comprehensive bioinformatics approaches. Extensive bioinformatics analyses demonstrated that CNGCs of Group IVa were distinct to those of other groups in gene structure and amino acid sequence of cyclic nucleotide-binding domain. A CNGC-specific motif that recognizes all identified plant CNGCs was generated. Phylogenetic analysis indicated that CNGC proteins of flowering plant species formed five groups. However, CNGCs of the non-vascular plant Physcomitrella patens clustered only in two groups (IVa and IVb), while those of the vascular non-flowering plant Selaginella moellendorffii gathered in four (IVa, IVb, I and II). These data suggest that Group IV CNGCs are most ancient and Group III CNGCs are most recently evolved in flowering plants. Furthermore, silencing analyses revealed that a set of CNGC genes might be involved in disease resistance and abiotic stress responses in tomato and function of SlCNGCs does not correlate with the group that they are belonging to. Our results indicate that Group IVa CNGCs are structurally but not functionally unique among plant CNGCs. PMID- 26546228 TI - Chemical Speciation and Quantitative Evaluation of Heavy Metal Pollution Hazards in Two Army Shooting Range Backstop Soils. AB - The chemical speciation and ecological risk assessment of heavy metals in two shooting range backstop soils in Korea were studied. Both soils were highly contaminated with Cd, Cu, Pb, and Sb. The chemical speciation of heavy metals reflected the present status of contamination, which could help in promoting management practices. We-rye soil had a higher proportion of exchangeable and carbonate bound metals and water-extractable Cd and Sb than the Cho-do soil. Bioavailable Pb represented 42 % of the total Pb content in both soils. A significant amount of Sb was found in the two most bioavailable fractions, amounting to ~32 % in the soil samples, in good agreement with the batch leaching test using water. Based on the values of ecological risk indices, both soils showed extremely high potential risk and may represent serious environmental problems. PMID- 26546227 TI - Functional and expression analyses of transcripts based on full-length cDNAs of Sorghum bicolor. AB - Sorghum bicolor is one of the most important crops for food and bioethanol production. Its small diploid genome and resistance to environmental stress make sorghum an attractive model for studying the functional genomics of the Saccharinae and other C4 grasses. We analyzed the domain-based functional annotation of the cDNAs using the gene ontology (GO) categories for molecular function to characterize all the genes cloned in the full-length cDNA library of sorghum. The sorghum cDNA library successfully captured a wide range of cDNA encoded proteins with various functions. To characterize the protein function of newly identified cDNAs, a search of their deduced domains and comparative analyses in the Oryza sativa and Zea mays genomes were carried out. Furthermore, genes on the sense strand corresponding to antisense transcripts were classified based on the GO of molecular function. To add more information about these genes, we have analyzed the expression profiles using RNA-Seq of three tissues (spikelet, seed and stem) during the starch-filling phase. We performed functional analysis of tissue-specific genes and expression analysis of genes of starch biosynthesis enzymes. This functional analysis of sorghum full-length cDNAs and the transcriptome information will facilitate further analysis of the Saccharinae and grass families. PMID- 26546229 TI - Mobility Studies of (14)C-Chlorpyrifos in Malaysian Oil Palm Soils. AB - The mobility of (14)C-chlorpyrifos using soil TLC was investigated in this study. It was found that chlorpyrifos was not mobile in clay, clay loam and peat soil. The mobility of (14)C-chlorpyrifos and non-labelled chlorpyrifos was also tested with silica gel TLC using three types of developing solvent hexane (100%), hexane:ethyl acetate (95:5, v/v); and hexane:ethyl acetate (98:2, v/v). The study showed that both the (14)C-labelled and non-labelled chlorpyrifos have the same Retardation Factor (Rf) for different developing solvent systems. From the soil column study on mobility of chlorpyrifos, it was observed that no chlorpyrifos residue was found below 5 cm depth in three types of soil at simulation rainfall of 20, 50 and 100 mm. Therefore, the soil column and TLC studies have shown similar findings in the mobility of chlorpyrifos. PMID- 26546230 TI - Efficient lipase-catalyzed Knoevenagel condensation: utilization of biocatalytic promiscuity for synthesis of benzylidene-indolin-2-ones. AB - Based on the screening of biocatalysts and reaction conditions including solvent, water content, temperature, enzyme loading, and reaction time, lipase from porcine pancreas (PPL) showed the prominent promiscuity for the Knoevenagel condensation between 1,3-dihydroindol-2-one heterocycle and aromatic aldehydes. Under the optimized procedure, both electron-withdrawing and electron-donating substituent of aldehydes substrates could react efficiently, and benzylidene indolin-2-ones were obtained in excellent yields (75.0-96.6%). Benzylidene indolin-2-ones derivatives were efficiently synthesized by the Knoevenagel condensation between various aromatic aldehydes and 1,3-dihydroindol-2-one catalyzed by lipase from porcine pancreas with excellent yields obtained. PMID- 26546231 TI - Bacterial thioredoxin and thioredoxin reductase as mediators for epigallocatechin 3-gallate-induced antimicrobial action. AB - Epigallocatechin 3-gallate (EGCG) is the most abundant catechin in green tea and may combat bacteria with few side-effects. Its selectivity for different bacterial infections remains unclear, and hence the identification of the underlying mechanism is of practical importance. Both the thioredoxin (Trx) system and the glutathione/glutaredoxin (Grx) system support bacterial growth. Some pathogenic bacteria are naturally deficient in the Grx system. We analyzed the effect of green tea extract (GTE) and EGCG on wild-type and null mutants of Escherichia coli with either Trx or Grx system deficiency and found that GTE and EGCG selected the Trx system as a target and killed the mutant that is exclusively dependent on Trx/Trx reductase (TrxR). EGCG inhibited the activity of both Trx1 and TrxR of E. coli in a dose-dependent and time-dependent manner. The IC50 values of EGCG for the reduced forms of E. coli Trx1/TrxR were ~ 3-4-fold lower than those for their non-reduced forms. The IC50 value of EGCG for the E. coli Trx1 system was 56-fold lower than that for the mammalian Trx1 system. The inhibition by EGCG of both Trx1 and TrxR of E. coli was irreversible. EGCG induced inactivation of E. coli Trx1 was a second-order process, and that of E. coli TrxR was an affinity-labeling process. The covalent binding sites for EGCG in E. coli Trx1 were Trp(28) , Trp(31) and Cys(32) , and in E. coli TrxR were Cys(135) and Cys(138) . Moreover, the sensitivity of Staphylococcus aureus to EGCG was similar to that of an E. coli mutant with Grx system deficiency. EGCG induced inactivation of Trx/TrxR in S. aureus coincided with suppressed growth of this virulent pathogen. Our findings suggest a role for EGCG-dependent Trx/TrxR inactivation in potentiating antibacterial activity of EGCG. PMID- 26546232 TI - John T. Yates, Jr. 1935-2015. AB - John T. Yates, Jr., professor at the University of Virginia, member of the US National Academy of Sciences, and pioneer of modern surface science passed away at the age of 80 on September 26, 2015. The scientific community has lost an exceptional scientist and gifted communicator, who was also heavily involved with scientific societies and academies, as well as evaluation procedures and conference organization. PMID- 26546233 TI - Selective toxicity of L-DOPA to dopamine transporter-expressing neurons and locomotor behavior in zebrafish larvae. AB - Dopamine signaling is conserved across all animal species and has been implicated in the disease process of many neurological disorders, including Parkinson's disease (PD). The primary neuropathology in PD involves the death of dopaminergic cells in the substantia nigra (SN), an anatomical region of the brain implicated in dopamine production and voluntary motor control. Increasing evidence suggests that the neurotransmitter dopamine may have a neurotoxic metabolic product (DOPAL) that selectively damages dopaminergic cells. This study was designed to test this theory of oxidative damage in an animal model of Parkinson's disease, using a transgenic strain of zebrafish with fluorescent labeling of cells that express the dopamine transporter. The pretectum and ventral diencephalon exhibited reductions in cell numbers due to L-DOPA treatment while reticulospinal neurons that do not express the DAT were unaffected, and this was partially rescued by monoamine oxidase inhibition. Consistent with the MPTP model of PD in zebrafish larvae, spontaneous locomotor behavior in L-DOPA treated animals was depressed following a 24-h recovery period, while visually-evoked startle response rates and latencies were unaffected. PMID- 26546235 TI - Transitions into practice: First patient care experiences of baccalaureate nursing students. AB - An essential component of the learning process for nursing and other disciplines in health professions education is the structuring of successful clinical experiences for beginning students. The purpose of this research study was to explore and describe first patient care experiences of baccalaureate nursing students in order to better understand student perspectives and perceptions. Data were collected from three cohorts of baccalaureate nursing in two university settings in the first semester following completion of first patient care experiences. A basic, exploratory qualitative approach with overtones of grounded theory was used for data collection and analysis. Three clear themes emerged from the data analysis. Participants experienced emotional responses of Anticipation, including fear, nervousness, and anxiety. The clinical experiences allowed Processing ~ Working Through, which was impacted by actions of instructors, nurses and patients. Participants developed Awareness as a result of their experiences. PMID- 26546234 TI - Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making. AB - The dominant approach to decision-making in public health policy for infectious diseases relies heavily on expert opinion, which often applies empirical evidence to policy questions in a manner that is neither systematic nor transparent. Although systematic reviews are frequently commissioned to inform specific components of policy (such as efficacy), the same process is rarely applied to the full decision-making process. Mathematical models provide a mechanism through which empirical evidence can be methodically and transparently integrated to address such questions. However, such models are often considered difficult to interpret. In addition, models provide estimates that need to be iteratively re evaluated as new data or considerations arise. Using the case study of a novel diagnostic for tuberculosis, a framework for improved collaboration between public health decision-makers and mathematical modellers that could lead to more transparent and evidence-driven policy decisions for infectious diseases in the future is proposed. The framework proposes that policymakers should establish long-term collaborations with modellers to address key questions, and that modellers should strive to provide clear explanations of the uncertainty of model structure and outputs. Doing so will improve the applicability of models and clarify their limitations when used to inform real-world public health policy decisions. PMID- 26546236 TI - CTLA-4+49 A/G polymorphism and antiglutamic acid decarboxylase antibody associated encephalopathy in Taiwanese children. AB - BACKGROUND: Anti-glutamic acid decarboxylase antibodies are associated with encephalopathy, an autoimmune central nervous system inflammatory disease. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)+49 A/G polymorphism has been shown to confer genetic susceptibility to positive anti-glutamic acid decarboxylase antibodies in patients with type 1 diabetes mellitus in Japan. We aimed to investigate the association of the CTLA-4+49 A/G (rs231775) polymorphism in Taiwanese children with anti-glutamic acid decarboxylase antibody-associated encephalopathy. METHODS: This was a case-control study from July 2011 to June 2012 performed at Chang Gung Children's Hospital in Taiwan. Genotyping of the CTLA-4+49 A/G polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Seventeen patients with anti-glutamic acid decarboxylase antibody-associated encephalopathy and 97 controls were enrolled. The genotype, allele and carrier frequencies of the CTLA-4+49 A/G polymorphism were equally distributed in the patients and controls, with no significant differences between the two groups. In addition, we found a positive trend between the level of anti-glutamic acid decarboxylase antibodies and the G allele of the CTLA-4+49 A/G polymorphism, although this trend was not statistically significant. CONCLUSIONS: Our results suggest that the CTLA-4+49 A/G (rs231775) polymorphism does not confer an increased susceptibility to anti-glutamic acid decarboxylase antibody-associated encephalopathy in Taiwanese children. PMID- 26546237 TI - A naming clutter and special type of spinal cord injury. PMID- 26546238 TI - Energy-Level Alignment for Single-Molecule Conductance of Extended Metal-Atom Chains. AB - The use of single-molecule junctions for various functions constitutes a central goal of molecular electronics. The functional features and the efficiency of electron transport are dictated by the degree of energy-level alignment (ELA), that is, the offset potential between the electrode Fermi level and the frontier molecular orbitals. Examples manifesting ELA are rare owing to experimental challenges and the large energy barriers of typical model compounds. In this work, single-molecule junctions of organometallic compounds with five metal centers joined in a collinear fashion were analyzed. The single-molecule i-V scans could be conducted in a reliable manner, and the EFMO levels were electrochemically accessible. When the electrode Fermi level (EF ) is close to the frontier orbitals (EFMO ) of the bridging molecule, larger conductance was observed. The smaller |EF -EFMO | gap was also derived quantitatively, unambiguously confirming the ELA. The mechanism is described in terms of a two level model involving co-tunneling and sequential tunneling processes. PMID- 26546239 TI - Green synthesis, characterization and drug delivery applications of a novel silver/carboxymethylcellulose - poly(acrylamide) hydrogel nanocomposite. AB - Biodegradable polymeric hydrogels are a unique class of macromolecular networks that can hold a large fraction of an aqueous solvent within their structures. They are particularly suitable for biomedical applications including controlled drug delivery, because of their ability to stimulate biological tissues. Many hydrogel-based networks have been designed and fabricated to meet the needs of pharmaceutical and medical fields. The investigation deals with the environment friendly synthesis of biodegradable semi interpenetrating hydrogel networks based on cross-linked poly(acrylamide) through an optimized rapid redox solution polymerization with N, N'Methylenebisacrylamide (MBA) in presence of Carboxymethylcellulose (CMC).The silver nanoparticles within hydrogel networks as nano reactors have been prepared by green synthesis via insitu reduction of silver nitrate (AgNO3) using Azadirachta Indica (Neem) plant extract under atmospheric conditions. The synthesized nanocomposites were characterised by FTIR spectroscopy, UV-Visible Spectroscopy, Scanning Electron Microscopy (SEM), Transmission electron microscopy (TEM) and Dynamic light scattering (DLS) technique. The thermal properties of the nanocomposite was analyzed by Thermogravimetric Analysis (TGA). The pH response and drug release profile of the synthesised biodegradable Silver-Hydrogel nanocomposite was investigated. Further, it was observed that physicochemical interaction between the polymeric nanocomposites and drug influences the degree of matrix swelling and therefore, its porosity and diffusion release process. PMID- 26546240 TI - Goldfish (Carassius auratus L.) as a model system to study the growth factors, receptors and transcription factors that govern myelopoiesis in fish. AB - The process of myeloid cell development (myelopoiesis) in fish has mainly been studied in three cyprinid species: zebrafish (Danio rerio), ginbuna carp (Carassius auratus langsdorfii) and goldfish (C. auratus, L.). Our studies on goldfish myelopoiesis have utilized in vitro generated primary kidney macrophage (PKM) cultures and isolated primary kidney neutrophils (PKNs) cultured overnight to study the process of macrophage (monopoiesis) and neutrophil (granulopoiesis) development and the key growth factors, receptors, and transcription factors that govern this process in vitro. The PKM culture system is unique in that all three subpopulations of macrophage development, namely progenitor cells, monocytes, and mature macrophages, are simultaneously present in culture unlike mammalian systems, allowing for the elucidation of the complex mixture of cytokines that regulate progressive and selective macrophage development from progenitor cells to fully functional mature macrophages in vitro. Furthermore, we have been able to extend our investigations to include the development of erythrocytes (erythropoiesis) and thrombocytes (thrombopoiesis) through studies focusing on the progenitor cell population isolated from the goldfish kidney. Herein, we review the in vitro goldfish model systems focusing on the characteristics of cell sub-populations, growth factors and their receptors, and transcription factors that regulate goldfish myelopoiesis. PMID- 26546241 TI - Variety support and exercise adherence behavior: experimental and mediating effects. AB - The purpose of this study was to examine the extent to which the provision of variety (i.e., variety support) is related to exercise behavior among physically inactive adults and the extent to which the 'experience of variety' mediates those effects. One hundred and twenty one inactive university students were randomly assigned to follow a high or low variety support exercise program for 6 weeks. Assessments were conducted at baseline, 3- and 6-weeks. Participants in the high variety support condition displayed higher levels of adherence to the exercise program than those in the low variety support condition [F(1, 116) = 5.55, p = .02, eta(p)(2) = .05] and the relationship between variety support and adherence was mediated by perceived variety (beta = .16, p < .01). Exercise related variety support holds potential to be an efficacious method for facilitating greater exercise adherence behaviors of previously inactive people by fostering perceptions of variety. PMID- 26546242 TI - Hey Mr. Sandman: dyadic effects of anxiety, depressive symptoms and sleep among married couples. AB - This study examined associations among anxiety, depressive symptoms, and sleep duration in a sample of middle-aged couples using the actor-partner interaction model with dyadic data. Self-report measures were completed independently by both partners as part of the health histories obtained during their annual preventive medical examinations in 2011 and 2012. Results showed that husbands' anxiety and depressive symptoms had a stronger effect on their wives' anxiety and depression than the other way around, but this was not moderated by one's own sleep duration. For both wives and husbands, higher levels of depressive symptoms and anxiety predicted shorter sleep duration for their partner 1 year later, although the effect of husbands' mental health on their wives' was again stronger. The findings suggest that sleep problems might better be treated as a couple-level phenomenon than an individual one, particularly for women. PMID- 26546243 TI - Personal responsibility, regret, and medical stigma among individuals living with lung cancer. AB - Understanding the degree to which adults with lung cancer perceive personal responsibility for their disease, personal regret for actions that may have contributed to lung cancer, and potential stigmatization from others is important, because these perceptions and experiences may be linked with treatment nonadherence, feelings of isolation, avoidance of healthcare providers, and poor quality of life. The purpose of this study was to evaluate rates and intensity of these types of experiences and to characterize the extent to which they are linked with smoking status and psychological adjustment in those living with lung cancer. Adults with lung cancer (N = 213) were recruited from two major cancer centers to complete a mail survey. Perceived responsibility was frequent in those who had ever smoked (74-80%), whereas regret and feelings of stigmatization were less frequent. When present, however, personal regret and stigmatization were associated with adverse psychological outcomes, particularly for never smokers. These results are consistent with the theory of stereotype threat and have clinical implications for management of people with lung cancer. PMID- 26546244 TI - Liraglutide vs. sitagliptin add-on to metformin treatment for type 2 diabetes mellitus: Short-term cost-per-controlled patient in Italy. AB - AIM: To estimate the short-term cost-per-controlled-patient with type 2 diabetes mellitus with liraglutide 1.2mg/day vs. sitagliptin 100mg/day as add-on treatment to metformin in Italy. METHODS: The percentage of controlled patients, i.e. with "HbA1c<7% without hypoglycemia and weight gain", at 26 and 52 weeks with liraglutide and sitagliptin, as well as at 78 weeks for patients switching at 52 weeks from sitagliptin to liraglutide or hypothetically continuing on sitagliptin were obtained from randomized clinical trials (RCT) and a meta-analysis. The treatment cost-per-controlled-patient was calculated from the perspective of the National Health System over a 26, 52- and 78-week time horizon. RESULTS: Despite the higher acquisition cost of liraglutide vs. sitagliptin, at 26 weeks liraglutide resulted in a lower cost-per-controlled-patient (?1460 vs. ?1820 - with efficacy from RCT - and ?1593 vs. ?2234 - with efficacy from a meta analysis), as well as at 52 weeks (?2627 vs. ?2649). At 78 weeks, in patients who have switched from sitagliptin to liraglutide at 52 weeks, the cost-per controlled-patient is also lower than that of patients continuing sitagliptin for 78 weeks (?2889 vs. ?3970). CONCLUSIONS: Due to higher efficacy, liraglutide is associated with better cost-benefit than sitagliptin at 26, 52 and 78 weeks. PMID- 26546245 TI - Active and passive smoking and risk of breast cancer: a meta-analysis. AB - Studies on active and passive tobacco smoking and breast cancer have found inconsistent results. A meta-analysis of observational studies on tobacco smoking and breast cancer occurrence was conducted based on systematic searches for studies with retrospective (case-control) and prospective (cohort) designs. Eligible studies were identified, and relative risk measurements were extracted for active and passive tobacco exposures. Random-effects meta-analyses were used to compute summary relative risks (SRR). Heterogeneity of results between studies was evaluated using the (I (2)) statistics. For ever active smoking, in 27 prospective studies, the SRR for breast cancer was 1.10 (95 % CI [1.09-1.12]) with no heterogeneity (I (2) = 0 %). In 44 retrospective studies, the SRR was 1.08 (95 % CI [1.02-1.14]) with high heterogeneity (I (2) = 59 %). SRRs for current active smoking were 1.13 (95 % CI [1.09-1.17]) in 27 prospective studies and 1.08 (95 % CI [0.97-1.20]) in 22 retrospective studies. The results were stable across different subgroup analyses, notably pre/post-menopause, alcohol consumption adjustments, including/excluding passive smokers from the referent group. For ever passive smoking, in 11 prospective studies, the SRR for breast cancer was 1.07 (95 % CI [1.02-1.13]) with no heterogeneity (I (2) = 1 %). In 20 retrospective studies, the SRR was 1.30 (95 % CI [1.10-1.54]) with high heterogeneity (I (2) = 74 %). Too few prospective studies were available for meaningful subgroup analyses. There is consistent evidence for a moderate increase in the risk of breast cancer in women who smoke tobacco. The evidence for a moderate increase in risk with passive smoking is more substantial than a few years ago. PMID- 26546248 TI - Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure. AB - Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF. We measured CRP using high-sensitivity particle-enhanced immunonephelometry in 16 patients with ischemic heart disease (previous myocardial infarction) and chronic systolic HF, defined as a left ventricular ejection fraction <= 50% and New York Heart Association class II-III symptoms. All subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent cardiopulmonary exercise testing using a symptom-limited ramp protocol. CRP levels predicted shorter exercise times (R = -0.65, p = 0.006), lower oxygen consumption (VO2) at the anaerobic threshold (R = -0.66, p = 0.005), and lower peak VO2 (R = -0.70, p = 0.002), reflecting worse cardiovascular performance. CRP levels also significantly correlated with an elevated ventilation/carbon dioxide production slope (R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope (R = -0.55, p = 0.026), and reduced end-tidal CO2 level at rest and with exercise (R = -0.759, p = 0.001 and R = -0.739, p = 0.001, respectively), reflecting impaired gas exchange. In conclusion, the intensity of systemic inflammation, measured as CRP plasma levels, is associated with cardiopulmonary exercise performance, in patients with ischemic heart disease and chronic systolic HF. These data provide the rationale for targeted anti-inflammatory treatments in HF. PMID- 26546247 TI - DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation. AB - Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury "from within" and chronic changes that may prove both morbid and fatal. The resolution phase of inflammation, once thought to be a passive event, is now known to be a highly regulated, active, and complex program that terminates the inflammatory response once the threat has been contained. Specialized pro-resolving mediators (SPMs) are biosynthesized from omega-3 essential fatty acids to resolvins, protectins, and maresins and from omega-6 fatty acids to lipoxins. Through cell-specific actions mediated through select receptors, these SPMs are potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages, promoting a return to tissue homeostasis. This process appears to be defective in several common human lung diseases, such as asthma and COPD, which are characterized by chronic unrestrained inflammation and significant associated morbidity. Here, we highlight translational research in animal models of disease and with human subjects that sheds light on this rapidly evolving area of science and review the molecular and cellular components of the resolution of lung inflammation. PMID- 26546249 TI - The study of Triadic Family Interactions: the Proposal of an Observational Procedure. AB - In the present article we provide an analytical review of 26 recent studies, which investigated triadic mother-father-child interactions through observational procedures. We focused on the methodological framework and compared the studies according to different criteria, in order to highlight the complexity of the object of study as well as the variety of dimensions and measures that have been used. Even if all the considered studies were designed to analyze triads, very few used coherently triadic categories; most of them focused on the individual members of the triad or on the parents with respect to the child. Joining the research that have stressed the importance of focusing on the reciprocal interactions of all members of the triad, we propose a methodological procedure that allows to describe the triad as a system without losing sight of the single participants and the simultaneity, interdependence, and processuality of their actions. PMID- 26546250 TI - Mapping Concepts of Agency in Educational Contexts. AB - The purpose of this conceptual paper is to explore and map the "espoused theories" (Argyris and Schon 1978) of agency used in educational contexts. More precisely, we limit the focus on the normative view of student agency assumed within dominant school practices, desired by educational practitioners, leaving out non-normative emerging agencies such as student agency of resistance. Agency is a "tricky" concept, and often scholars who use the concept of agency do not define or operationalize it (e.g., Archer 2000). One reason is that there is no consensus among scholars about the notion of agency, especially when applied to educational contexts (Hitlin and Elder Sociological Theory, 25 (2), 170-191, 2007). Moreover, the recent neoliberal framing of individuals' agency as fully autonomous, flexible, and self-entrepreneur is adding the dilemma of agency manipulation in the sphere of education (Gershon 2011; Sidorkin 2004). To tackle this dilemma in educational contexts, we suggest to further interrogating the normative notion of agency in all its modes and develop a more nuanced conceptualization. We hope that such conceptualization would produce an understanding of the diverse manifestations and definitions of agency within a human ideal, educational content, behaviors, and social settings. We observed diverse uses of the normative term "agency" in educational discourse. We examined the term as used by researchers and practitioners. We also looked at the different ways it has been used in philosophical discussions of education, political framing of the civic role of schooling, disciplinary policy statements, school mission statements, and in everyday common use. It is worthy to note that our categorization of the use and meaning of the normative term "agency" depends on the scholars' epistemological paradigmatic assumptions, socio-political and historical situatedness, and ontological projects being translated into diverse scholarships of education. As a result of our research, we suggest four major normative conceptual frameworks related to agency mainly being adopted in educational contexts that we labeled as: 1) instrumental, 2) effortful, 3) dynamically emergent, and 4) authorial. In this paper, we discuss these normative approaches to agency as we compare and contrast the assumptions and their consequences for the current field of education, mostly from a point of view of authorial definition of agency (our bias). PMID- 26546252 TI - Overexpressed Rce1 is positively correlated with tumor progression and predicts poor prognosis in prostate cancer. AB - Ras and a-factor-converting enzyme 1 (Rce1) have been reported to play a key role in the proteolysis processing of Ras proteins. The present study investigated the prognostic significance of Rce1 in patients with prostate cancer (PCa). The expressions of the mRNA and protein of Rce1 were analyzed in 12 pairs of PCa and benign prostatic hyperplasia (BPH) by quantitative real-time polymerase chain reaction and Western blotting, respectively. Immunohistochemistry was used to examine expression of Rce1 protein in 74 PCa tissues and 30 BPH tissues. The association between Rce1 expression and the specific clinicopathologic features was evaluated by chi(2) tests. Kaplan-Meier and Cox proportional hazards regression models were used to analyze the data. We found that expression of Rce1 mRNA and protein was markedly higher in PCa tissues than in paired BPH tissues. Expression of Rce1 in PCa was strongly associated with clinicopathologic features. It was detected in 69 (93.24%) of 74 PCa tissues by immunohistochemistry, and it was found to be associated with Gleason score (P = .013), T class (P = .015), and distant metastasis (P = .044). Patients with PCa having higher Rce1 expression had substantially shorter survival times than patients with lower Rce1 expression. Univariate and multivariate analysis revealed that Rce1 was an independent prognostic factor. In conclusion, our study suggests that expression of Rce1 can serve as an independent biomarker for the prognosis of PCa patients. PMID- 26546253 TI - IAEA INTERCOMPARISON EXERCISES OF THYROID MEASUREMENT: PERFORMANCE OF LATIN AMERICAN AND CARIBBEAN LABORATORIES. AB - (131)I is widely used in Latin America and Caribbean Region in the field of nuclear medicine and has been recognised as one of the main sources of potential intake of radionuclides by the staff. The In Vivo Monitoring laboratory of the Institute for Radiation Protection and Dosimetry (IRD-CNEN-Brazil) organised three intercomparison exercises (2005, 2009 and 2013) in the scope of IAEA technical cooperation projects RLA9049 and RLA9066 aimed to disseminate and harmonise the technique for measuring (131)I in the human thyroid. The number of participants in Latin America increased from 9 to 20 institutions from 7 and 13 countries, respectively, over the last 10 y. The participants have improved significantly their ability on the in vivo measurement technique. In the 2013 round all laboratories which reported results presented performances in an acceptable range according to the ISO criteria indicating the benefit of such exercises in the region. PMID- 26546254 TI - Borrowing of strength and study weights in multivariate and network meta analysis. AB - Multivariate and network meta-analysis have the potential for the estimated mean of one effect to borrow strength from the data on other effects of interest. The extent of this borrowing of strength is usually assessed informally. We present new mathematical definitions of 'borrowing of strength'. Our main proposal is based on a decomposition of the score statistic, which we show can be interpreted as comparing the precision of estimates from the multivariate and univariate models. Our definition of borrowing of strength therefore emulates the usual informal assessment. We also derive a method for calculating study weights, which we embed into the same framework as our borrowing of strength statistics, so that percentage study weights can accompany the results from multivariate and network meta-analyses as they do in conventional univariate meta-analyses. Our proposals are illustrated using three meta-analyses involving correlated effects for multiple outcomes, multiple risk factor associations and multiple treatments (network meta-analysis). PMID- 26546255 TI - A joint Bayesian approach for the analysis of response measured at a primary endpoint and longitudinal measurements. AB - Joint mixed modeling is an attractive approach for the analysis of a scalar response measured at a primary endpoint and longitudinal measurements on a covariate. In the standard Bayesian analysis of these models, measurement error variance and the variance/covariance of random effects are a priori modeled independently. The key point is that these variances cannot be assumed independent given the total variation in a response. This article presents a joint Bayesian analysis in which these variance terms are a priori modeled jointly. Simulations illustrate that analysis with multivariate variance prior in general lead to reduced bias (smaller relative bias) and improved efficiency (smaller interquartile range) in the posterior inference compared with the analysis with independent variance priors. PMID- 26546256 TI - Bayesian analysis of multi-type recurrent events and dependent termination with nonparametric covariate functions. AB - Multi-type recurrent event data occur frequently in longitudinal studies. Dependent termination may occur when the terminal time is correlated to recurrent event times. In this article, we simultaneously model the multi-type recurrent events and a dependent terminal event, both with nonparametric covariate functions modeled by B-splines. We develop a Bayesian multivariate frailty model to account for the correlation among the dependent termination and various types of recurrent events. Extensive simulation results suggest that misspecifying nonparametric covariate functions may introduce bias in parameter estimation. This method development has been motivated by and applied to the lipid-lowering trial component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. PMID- 26546257 TI - What are the appropriate methods for analyzing patient-reported outcomes in randomized trials when data are missing? AB - Subjective health measurements using Patient Reported Outcomes (PRO) are increasingly used in randomized trials, particularly for patient groups comparisons. Two main types of analytical strategies can be used for such data: Classical Test Theory (CTT) and Item Response Theory models (IRT). These two strategies display very similar characteristics when data are complete, but in the common case when data are missing, whether IRT or CTT would be the most appropriate remains unknown and was investigated using simulations. We simulated PRO data such as quality of life data. Missing responses to items were simulated as being completely random, depending on an observable covariate or on an unobserved latent trait. The considered CTT-based methods allowed comparing scores using complete-case analysis, personal mean imputations or multiple imputations based on a two-way procedure. The IRT-based method was the Wald test on a Rasch model including a group covariate. The IRT-based method and the multiple-imputations-based method for CTT displayed the highest observed power and were the only unbiased method whatever the kind of missing data. Online software and Stata(r) modules compatibles with the innate mi impute suite are provided for performing such analyses. Traditional procedures (listwise deletion and personal mean imputations) should be avoided, due to inevitable problems of biases and lack of power. PMID- 26546258 TI - Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C Disease. AB - Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/beta(0)-thalassemia, and hemoglobin S/beta(+)-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy. PMID- 26546259 TI - Safety and immunogenicity of ricin vaccine, RVEcTM, in a Phase 1 clinical trial. AB - Ricin is a potent toxin and potential bioterrorism weapon for which no specific licensed countermeasures are available. We report the safety and immunogenicity of the ricin vaccine RVEcTM in a Phase 1 (N=30) multiple-dose, open-label, non placebo-controlled, dose-escalating (20, 50, and 100MUg), single-center study. Each subject in the 20- and 50-MUg dose groups (n=10 for each group) received three injections at 4-week intervals and was observed carefully for untoward effects of the vaccine; blood was drawn at predetermined intervals after each dose for up to 1 year. RVEcTM was safe and well tolerated at the 20- and 50-MUg doses. The most common adverse events were pain at the injection site and headache. Of the 10 subjects who received a single 100-MUg dose, two developed elevated creatine phosphokinase levels, which resolved without sequelae. No additional doses were administered to subjects in the 100-MUg group. Immunogenicity of the vaccine was evaluated by measuring antibody response using the well standardized enzyme-linked immunosorbent assay (ELISA) and toxin neutralization assay (TNA). Of the subjects in the 20- and 50-MUg dose groups, 100% achieved ELISA anti-ricin IgG titers of 1:500 to 1:121,500 and 50% produced neutralizing anti-ricin antibodies measurable by TNA. Four subjects in the 50-MUg group received a single booster dose of RVEcTM 20-21 months after the initial dose. The single booster was safe and well tolerated, resulting in no serious adverse events, and significantly enhanced immunogenicity of the vaccine in human subjects. Each booster recipient developed a robust anamnestic response with ELISA anti-ricin IgG titers of 1:13,500 to 1:121,500 and neutralizing antibody titers of 1:400 to 1:3200. Future studies will attempt to optimize dose, scheduling, and route of administration. This study is registered at clinicaltrials.gov (NCT01317667 and NCT01846104). PMID- 26546260 TI - From current vaccine recommendations to everyday practices: An analysis in five sub-Saharan African countries. AB - BACKGROUND: Estimates of WHO and UNICEF vaccination coverage may provide little insight into the extent to which vaccinations are administered on time. Yet, lack of adherence to the recommended age to receive a specific vaccination may have detrimental health consequences. For example, delays in receiving vaccination will prolong the risk of lack of protection, often when disease risk is highest, such as during early infancy. We estimated the reported age at vaccination, and vaccine coverage at different ages in children from five sub-Saharan African countries. METHODS: We analyzed data from the latest Demographic and Health Programme databases available for Burkina Faso 2010 (n=15,044 observations), Ghana 2008 (n=2992), Kenya 2008-9 (n=6079), Senegal 2010-11 (n=12,326), and Tanzania 2010 (n=8023). We assessed, amongst vaccinees, the exact age when vaccine was administered for the three infant doses of pentavalent vaccine (DTP) and the first dose of measles-containing-vaccine (MCV), as well as the proportion of children immunized with these antigens by a certain age. Vitamin A supplementation (VAS) coverage was evaluated as a potential contact visit for vaccine introduction. RESULTS: For all DTP doses, the median intervals between recommended and actual ages of receiving vaccination ranged from 12, 17 and 23 days in Kenya, to 22, 33 and 45 days in Senegal. MCV was mostly given during the recommended age of 9 months. In each country, there was a large discrepancy in the median age at DTP vaccination between regions. VAS coverage in young children ranged from 30.3% in Kenya to 78.4% in Senegal, with large variations observed between areas within each study country. CONCLUSION: In the context of new vaccine introduction, age of children at vaccination should be monitored to interpret data on vaccine-preventable disease burden, vaccine effectiveness, and vaccine safety, and to adapt targeted interventions and messages. PMID- 26546261 TI - The efficacy of a novel vaccine approach using tumor cells that ectopically express a codon-optimized murine GM-CSF in a murine tumor model. AB - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that is known to facilitate vaccine efficacy by promoting the development and prolongation of both humoral and cellular immunity. Here, we investigated a novel vaccine approach using a human papillomavirus (HPV) 16 E6/E7-transformed cell line, TC-1, that ectopically expresses a codon optimized 26-11-2015 murine GM-CSF (cGM-CSF). Ectopically expressing cGM-CSF in TC-1 (TC-1/cGM) cells significantly increased expression of a GM-CSF that was functionally identical to wt GM-CSF by 9-fold compared with ectopically expressed wild type GM-CSF in TC-1 cells (TC-1/wt). Mice vaccinated with irradiated TC 1/cGM cells exhibited enhanced survival compared with mice vaccinated with TC 1/wt cells when both groups were subsequently injected with live TC-1. Consistently, mice vaccinated with irradiated TC-1/cGM cells exhibited stronger IFN-gamma production in HPV E7-specific CD8(+) T cells. More dendritic cells were recruited to the draining lymph nodes (dLNs) of mice vaccinated with TC-1/cGM cells than C-1/wt cells. Regarding dLN cell recall responses, both proliferation and IFN-gamma production in the HPV E7-specific CD8(+) T cells were enhanced in mice that were vaccinated with TC-1/cGM cells. Our results demonstrate that a novel practical molecular strategy utilizing a codon-optimized GM-CSF gene overcomes the limitation and improves the efficacy of tumor cell-based vaccines. PMID- 26546262 TI - Effectiveness of monovalent rotavirus vaccine in a high-income, predominant-use setting. AB - BACKGROUND AND OBJECTIVES: We assessed monovalent rotavirus (RV1) vaccine effectiveness (VE) in a high-income setting with RV1 predominant use, and examined the burden of pediatric rotavirus gastroenteritis following the implementation of an RV1-only vaccination program. METHODS: We conducted active rotavirus gastroenteritis surveillance among children 8 weeks to <3 years of age at three hospitals. Participant information and vaccination histories were collected via parent/guardian interview and medical records. Stool specimens were tested for rotavirus; positive specimens were genotyped. The effect of increasing RV1 coverage on rotavirus prevalence was examined as a weekly time series via binomial regression with a log link function, using either categorical season or mean 2-dose rotavirus seasonal vaccine coverage as the exposure variable. As compared with RV1 vaccine formulation, rotavirus genotypes were classified as homotypic, partly-heterotypic, or heterotypic; prevalence of each was compared by season. A test-negative case-control design was used to examine RV1 VE against hospitalization or emergency visits. RESULTS: We enrolled 866 participants in active surveillance; of these, 384 (44.3%) were eligible for VE analyses. After adjustment for season, we detected a 70.1% (95% CI: 21.9%, 88.6%) relative decrease in rotavirus prevalence in the 2013-14 season compared with 2012-13 season. On average, a 1% increase in >=2-dose rotavirus coverage among children 1 year of age was associated with a 3.8% (95% CI: 1.8%, 5.8%) relative decrease in rotavirus prevalence. Rotavirus homotypic strain prevalence decreased, with 77% (95% CI: 68%, 89%) versus 8% (95% CI: 0%, 36%) prevalence during the 2011-12 and 2013-14 seasons, respectively. Adjusted 2-dose RV1 VE was 91.2% (95% CI: 61.6%, 98.0%). CONCLUSIONS: RV1 vaccine was highly effective to prevent rotavirus hospitalizations and emergency visits among children <3 years of age in a high income setting with its predominant use. Our estimates were similar to high income settings with concurrent RV1 and pentavalent vaccine use. PMID- 26546263 TI - Response to pneumococcal polysaccharide vaccination in patients with chronic and allergic aspergillosis. AB - INTRODUCTION: Pneumococcal infection causes significant morbidity in patients with underlying lung disease, and vaccination has been associated with reduced disease rates. Response to vaccination has not been studied in chronic lung conditions characterised by ongoing infection or inflammation like chronic pulmonary aspergillosis (CPA). METHODS: In a prospective observational study, consecutive patients with CPA, allergic aspergillosis and bronchiectasis attending a national referral centre received pneumococcal 23-valent polysaccharide vaccine (PPV-23) and had pre- and post-vaccination antibody concentrations quantified as part of routine clinical care. Serotype-specific pneumococcal IgG antibodies were quantified for 12 serotypes using a multiplex microsphere assay. A protective response was defined as a level of >1.3MUg/mL or a >= fourfold rise in concentration for >=70% of serotypes, pre to post vaccination. C-reactive protein, Immunoglobulins and mannose binding lectin (MBL) levels were measured and correlated to vaccine response. RESULTS: A total of 318 patients were enrolled. In vaccine-naive patients (n=127), the lowest pre vaccination levels were seen with serotypes 1 and 4 and the highest with serotype 19A. A protective response post-vaccination was seen in 50% of patients. The poorest responses were observed with serotypes 1, 3 and 4. Levels of C-reactive protein did not affect efficacy. Profound MBL deficiency was found in 28.8%; there were no significant differences in response to vaccination in patients with or without MBL deficiency. Post-vaccination serotype-specific concentrations waned gradually, however they were still elevated compared to pre-vaccination after 2-5 years. CONCLUSIONS: Patients with chronic and allergic aspergillosis exhibited a poor response to PPV-23 vaccination compared to healthy adults. An alternative vaccination strategy or delay of vaccination until their underlying condition is better controlled, e.g. after treatment with antifungals may result in better response. PMID- 26546264 TI - Neutralizing epitopes mapping of human adenovirus type 14 hexon. AB - Human adenoviruses 14 (HAdV-14) caused several clusters of acute respiratory disease (ARD) outbreaks in both civilian and military settings. The identification of the neutralizing epitopes of HAdV-14 is important for the surveillance and control of infection. Since the previous studies had indicated that the adenoviruses neutralizing epitopes were likely to be exposed on the surface of the hexon, four epitope peptides, A14R1 (residues 141-157), A14R2 (residues 181-189), A14R4 (residues 252-260) and A14R7 (residues 430-442) were predicted and mapped onto the 3D structures of hexon by homology modeling approach. Then the four peptides were synthesized, and all the four putative epitopes were identified as neutralizing epitopes by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally we incorporated the four epitopes into human adenoviruses 3 (HAdV-3) vectors using the "antigen capsid incorporation" strategy, and two chimeric adenoviruses, A14R2A3 and A14R4A3, were successfully obtained which displayed A14R2 and A14R4 respectively on the hexon surface of HAdV-3 virions. Further analysis showed that the two chimeric viruses antiserum could neutralize both HAdV-14 and HAdV-3 infection. The neutralization titers of anti-A14R4A3 group were significantly higher than the anti-KLH-A14R4 group (P=0.0442). These findings have important implications for the development of peptide-based broadly protective HAdV-14 and HAdV-3 bivalent vaccine. PMID- 26546265 TI - Nonlinear optical behavior of Li n F (n = 2-5) superalkali clusters. AB - Hyperlithiated clusters are known for their unusual bonding characteristics and lower ionization potentials. This study reports nonlinear optical (NLO) properties of a series of hyperlithiated clusters, Li n F (n = 2-5) for the first time. The structures of small Li n F (n = 2-5) clusters, obtained using second order Moller-Plesset perturbative method, are found to be stable against eliminations of F, F?, and LiF. These Li n F species are stabilized by both ionic as well as covalent interactions. Our study shows that Li n F species can be thought of as superalkali-halogen (Li n - F) clusters but belong to the class of superalkalies themselves. These clusters may also possess alkalide and/or electride characteristics due to excess electrons. The dipole moment, mean polarizability, and hyperpolarizability suggest their significant NLO responses which are explained using the highest occupied molecular orbital surfaces and TD DFT analysis. The exceptionally large hyperpolarizability of Li2F (~10(5) a.u.) and its electride characteristics are particularly highlighted. This study may guide the researchers in the design of novel materials with significant NLO responses useful for electro-optical applications. Graphical Abstract Li2F superalkali resemble an electride in which the excess electron is pushed out by Li2 (+) moiety, leading to its high hyperpolarizability of order of 10(5) a.u. PMID- 26546266 TI - Imaging the Cemento-Enamel Junction Using a 20-MHz Ultrasonic Transducer. AB - The cemento-enamel junction (CEJ), which is the intersection between enamel and cementum, is an important landmark in the diagnosis of periodontal disease. Pulse echo ultrasound was used to image the CEJs of six porcine lower central incisors with a single 20-MHz transducer. A notch was longitudinally created on the enamel as a stable marker, from which the CEJ was measured. Data were acquired along the tooth's axis at 0.4-mm intervals. Time-distance data were bandpass-filtered to enhance signal-to-noise ratio and record density was increased fourfold to 0.1-mm spacing by a frequency-distance interpolation scheme. Reflections from the CEJ were unambiguously identified along with those from enamel, dentin and cementum. The notch-CEJ distances measured by the ultrasound and micro-computed tomography methods correlated strongly (r = 0.996, p < 0.05) and were in good agreement with the 95% lines of agreement between -0.49 and 0.17 mm, as statistically determined by Bland-Altman analysis. The results indicate the potential of ultrasound to be a reliable and non-ionizing technique to image the CEJ. PMID- 26546267 TI - The direction of cross affects [corrected] obesity after puberty in male but not female offspring. AB - BACKGROUND: We investigated parent-of-origin and allele-specific expression effects on obesity and hepatic gene expression in reciprocal crosses between the Berlin Fat Mouse Inbred line (BFMI) and C57Bl/6NCrl (B6N). RESULTS: We found that F1-males with a BFMI mother developed 1.8 times more fat mass on a high fat diet at 10 weeks than F1-males of a BFMI father. The phenotype was detectable from six weeks on and was preserved after cross-fostering. RNA-seq data of liver provided evidence for higher biosynthesis and elongation of fatty acids (p = 0.00635) in obese male offspring of a BFMI mother versus lean offspring of a BFMI father. Furthermore, fatty acid degradation (p = 0.00198) and the peroxisome pathway were impaired (p = 0.00094). The circadian rhythm was affected as well (p = 0.00087). Among the highest up-regulated protein coding genes in obese males were Acot4 (1.82 fold, p = 0.022), Cyp4a10 (1.35 fold, p = 0.026) and Cyp4a14 (1.32 fold, p = 0.012), which hydroxylize fatty acids and which are known to be increased in liver steatosis. Obese males showed lower expression of the genetically imprinted and paternally expressed 3 (Peg3) gene (0.31 fold, p = 0.046) and higher expression of the androgen receptor (Ar) gene (2.38 fold, p = 0.068). Allelic imbalance was found for expression of ATP-binding cassette transporter gene Abca8b. Several of the differentially expressed genes contain estrogen response elements. CONCLUSIONS: Parent-of-origin effects during gametogenesis and/or fetal development in an obese mother epigenetically modify the transcription of genes that lead to enhanced fatty acid synthesis and impair beta-oxidation in the liver of male, but not female F1 offspring. Down-regulation of Peg3 could contribute to trigger this metabolic setting. At puberty, higher amounts of the androgen receptor and altered access to estrogen response elements in affected genes are likely responsible for male specific expression of genes that were epigenetically triggered. A suggestive lack of estrogen binding motifs was found for highly down regulated genes in adult hepatocytes of obese F1 males (p = 0.074). PMID- 26546269 TI - Using in vivo imaging to measure RNA mobility in Xenopus laevis oocytes. AB - RNA localization in the Xenopus oocyte is responsible for the establishment of polarity during oogenesis as well as the specification of germ layers during embryogenesis. However, the inability to monitor mRNA localization in live vertebrate oocytes has posed a major barrier to understanding the mechanisms driving directional transport. Here we describe a method for imaging MS2 tagged RNA in live Xenopus oocytes to study the dynamics of RNA localization. We also focus on methods for implementing and analyzing FRAP data. This protocol is optimized for imaging of the RNAs in stage II oocytes but it can be adapted to study dynamics of other molecules during oogenesis. Using this approach, mobility can be measured in different regions of the oocyte, enabling the direct observation of molecular dynamics throughout the oocyte. PMID- 26546268 TI - The Wnts of change: How Wnts regulate phenotype switching in melanoma. AB - The outgrowth of metastatic and therapy-resistant subpopulations in cancer remains a critical barrier for the successful treatment of this disease. In melanoma, invasion and proliferation are uncoupled, such that highly proliferative melanoma cells are less likely to be invasive, and vice versa. The transition between each state is likely a dynamic rather than a static, permanent change. This is referred to as "phenotype switching". Wnt signaling pathways drive phenotypic changes and promote therapy resistance in melanoma, as well as play roles in the modulation of the immune microenvironment. Three Wnt signaling pathways play a role in melanoma progression, canonical (beta-catenin dependent), polar cell polarity (PCP), and the Wnt/Ca2+ pathway. Here we summarize phenotype plasticity and its role in therapy resistance and immune evasion. Targeting the Wnt signaling pathways may be an effective way to overcome tumor plasticity in melanoma. PMID- 26546270 TI - Tracking the in vivo release of bioactive NRG from PLGA and PEG-PLGA microparticles in infarcted hearts. AB - The growth factor neuregulin (NRG) is one of the most promising candidates in protein therapy as potential treatment for myocardial infarction (MI). In the last few years, biomaterial based delivery systems, such as polymeric microparticles (MPs) made of poly(lactic co glycolic acid) and polyethylene glycol (PLGA and PEG-PLGA MPs), have improved the efficacy of protein therapy in preclinical studies. However, no cardiac treatment based on MPs has yet been commercialized since this is a relatively new field and total characterization of polymeric MPs remains mandatory before they reach the clinical arena. Therefore, the objective of this study was to characterize the in vivo release, bioactivity and biodegradation of PLGA and PEG-PLGA MPs loaded with biotinylated NRG in a rat model of MI. The effect of PEGylation in the clearance of the particles from the cardiac tissue was also evaluated. Interestingly, MPs were detected in the cardiac tissue for up to 12 weeks after administration. In vivo release analysis showed that bNRG was released in a controlled manner throughout the twelve week study. Moreover, the biological cardiomyocyte receptor (ErbB4) for NRG was detected in its activated form only in those animals treated with bNRG loaded MPs. On the other hand, the PEGylation strategy was effective in diminishing phagocytosis of these MPs compared to noncoated MPs in the long term (12 weeks after injection). Taking all this together, we report new evidence in favor of the use of polymeric PLGA and PEG-PLGA MPs as delivery systems for treating MI, which could be soon included in clinical trials. PMID- 26546271 TI - Disarmed anthrax toxin delivers antisense oligonucleotides and siRNA with high efficiency and low toxicity. AB - Inefficient cytosolic delivery and vector toxicity contribute to the limited use of antisense oligonucleotides (ASOs) and siRNA as therapeutics. As anthrax toxin (Atx) accesses the cytosol, the purpose of this study was to evaluate the potential of disarmed Atx to deliver either ASOs or siRNA. We hypothesized that this delivery strategy would facilitate improved transfection efficiency while eliminating the toxicity seen for many vectors due to membrane destabilization. Atx complex formation with ASOs or siRNA was achieved via the in-frame fusion of either Saccharomyces cerevisiae GAL4 or Homo sapien sapien PKR (respectively) to a truncation of Atx lethal factor (LFn), which were used with Atx protective antigen (PA). Western immunoblotting confirmed the production of: LFN-GAL4, LFn PKR and PA which were detected at ~45.9 kDa, ~37 kDa, and ~83 kDa respectively and small angle neutron scattering confirmed the ability of PA to form an annular structure with a radius of gyration of 7.0 +/- 1.0 nm when placed in serum. In order to form a complex with LFn-GAL4, ASOs were engineered to contain a double stranded region, and a cell free in vitro translation assay demonstrated that no loss of antisense activity above 30 pmol ASO was evident. The in vitro toxicity of both PA:LFn-GAL4:ASO and PA:LFn-PKR:siRNA complexes was low (IC50>100 MUg/mL in HeLa and Vero cells) and subcellular fractionation in conjunction with microscopy confirmed the detection of LFn-GAL4 or LFn-PKR in the cytosol. Syntaxin5 (Synt5) was used as a model target gene to determine pharmacological activity. The PA:LFn-GAL4:ASO complexes had transfection efficiency approximately equivalent to Nucleofection(r) over a variety of ASO concentrations (24h post transfection) and during a 72 h time course. In HeLa cells, at 200 pmol ASO (with PA:LFN-GAL4), 5.4 +/- 2.0% Synt5 expression was evident relative to an untreated control after 24h. Using 200 pmol ASOs, Nucleofection(r) reduced Synt5 expression to 8.1 +/- 2.1% after 24h. PA:LFn-GAL4:ASO transfection of non- or terminally differentiated THP-1 cells and Vero cells resulted in 35.2 +/- 19.1%, 36.4 +/- 1.8% and 22.9 +/- 6.9% (respectively) Synt5 expression after treatment with 200 pmol of ASO and demonstrated versatility. Nucleofection(r) with Stealth RNAiTM siRNA reduced HeLa Synt5 levels to 4.6 +/- 6.1% whereas treatment with the PA:LFn PKR:siRNA resulted in 8.5 +/- 3.4% Synt5 expression after 24h (HeLa cells). These studies report for the first time an ASO and RNAi delivery system based upon protein toxin architecture that is devoid of polycations. This system may utilize regulated membrane back-fusion for the cytosolic delivery of ASOs and siRNA, which would account for the lack of toxicity observed. High delivery efficiency suggests further in vivo evaluation is warranted. PMID- 26546272 TI - Decline in objective physical activity over a 10-year period in a Japanese elementary school. AB - BACKGROUND: The purpose of this study was to examine the change in accelerometer derived daily physical activity (PA) and activity record-derived daily activities over a 10-year period in urban elementary schoolchildren in Japan. METHODS: A total of 233 sixth-grade children (11-12 years old) in a same elementary school in Kyoto participated in the study (n = 125 and 108 in 1999 and 2009, respectively). The participant rate is 91.9 and 98.2% in 1999 and 2009, respectively. The size and shape of the school district was not changed. The children were instructed to wear an accelerometer for 5 consecutive days of weekday and to keep minute-by-minute 24-h activity records with the assistance of their parents. The school-day scheduling was similar between 1999 and 2009 (29 and 27 sessions of 45-min class per week, respectively). RESULTS: From 1999 to 2009, step counts considerably decreased (20,832 vs. 12,237 steps per day in boys and 16,087 vs. 10,748 steps per day in girls; P < 0.001) with concomitant significant decreases in total energy expenditure (P = 0.011), activity energy expenditure (P < 0.001), and physical activity level (P < 0.001). Time spent playing outdoors and walking to school were also significantly less in 2009 than 1999 (P < 0.001). Accelerometer-measured PA was significantly associated with the amount of time spent playing outdoors and walking to school. CONCLUSIONS: These results indicate that elementary schoolchildren in 2009 spend less time playing outdoors and walking to school, perform less PA, and take fewer steps than children of a decade ago. PMID- 26546273 TI - Evidence-based medicine: is it a bridge too far? AB - AIMS: This paper aims to describe the contextual factors that gave rise to evidence-based medicine (EBM), as well as its controversies and limitations in the current health context. Our analysis utilizes two frameworks: (1) a complex adaptive view of health that sees both health and healthcare as non-linear phenomena emerging from their different components; and (2) the unified approach to the philosophy of science that provides a new background for understanding the differences between the phases of discovery, corroboration, and implementation in science. RESULTS: The need for standardization, the development of clinical epidemiology, concerns about the economic sustainability of health systems and increasing numbers of clinical trials, together with the increase in the computer's ability to handle large amounts of data, have paved the way for the development of the EBM movement. It was quickly adopted on the basis of authoritative knowledge rather than evidence of its own capacity to improve the efficiency and equity of health systems. The main problem with the EBM approach is the restricted and simplistic approach to scientific knowledge, which prioritizes internal validity as the major quality of the studies to be included in clinical guidelines. As a corollary, the preferred method for generating evidence is the explanatory randomized controlled trial. This method can be useful in the phase of discovery but is inadequate in the field of implementation, which needs to incorporate additional information including expert knowledge, patients' values and the context. CONCLUSION: EBM needs to move forward and perceive health and healthcare as a complex interaction, i.e. an interconnected, non-linear phenomenon that may be better analysed using a variety of complexity science techniques. PMID- 26546274 TI - Validity of flounce sign to rule out medial meniscus tear in knee arthroscopy. AB - BACKGROUND: The meniscal flounce is wavy fold in free inner border of meniscus seen during knee arthroscopy. The presence of this flounce in medial meniscus has been found to be highly predictive of normal medial meniscus. With meniscus related symptoms being commonest indication for undergoing knee arthroscopy, presence or absence of medial meniscus flounce, can be a good guiding sign. In this study, we aimed to validate the significance of the flounce sign in ruling out medial meniscus tear. METHODS: A prospective study was undertaken to validate the significance of flounce sign. There were 62 patients who underwent arthroscopic surgery of the knee over the duration of one and half years. Free inner margin of medial meniscus as seen through anterolateral portal was recorded for the presence or absence of flounce. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of this sign was then calculated for diagnosing normal medial meniscus. Significance was tested with chi square test with 95 % confidence interval. RESULTS: A total of 62 cases were included. The sensitivity, specificity, PPV, NPV and accuracy of flounce sign was found to be 67.64 %, 92.85 %, 92 %, 70.27 % and 79.03 % respectively, and the result was significant (p value = 0.0001). CONCLUSION: The flounce sign has been shown to have high diagnostic value. Use of it in routine knee arthroscopy can be helpful, particularly during screening procedure and in exploring tears which are usually not seen easily through routine portals. PMID- 26546275 TI - Drought and leaf herbivory influence floral volatiles and pollinator attraction. AB - The effects of climate change on species interactions are poorly understood. Investigating the mechanisms by which species interactions may shift under altered environmental conditions will help form a more predictive understanding of such shifts. In particular, components of climate change have the potential to strongly influence floral volatile organic compounds (VOCs) and, in turn, plant pollinator interactions. In this study, we experimentally manipulated drought and herbivory for four forb species to determine effects of these treatments and their interactions on (1) visual plant traits traditionally associated with pollinator attraction, (2) floral VOCs, and (3) the visitation rates and community composition of pollinators. For all forbs tested, experimental drought universally reduced flower size and floral display, but there were species specific effects of drought on volatile emissions per flower, the composition of compounds produced, and subsequent pollinator visitation rates. Moreover, the community of pollinating visitors was influenced by drought across forb species (i.e. some pollinator species were deterred by drought while others were attracted). Together, these results indicate that VOCs may provide more nuanced information to potential floral visitors and may be relatively more important than visual traits for pollinator attraction, particularly under shifting environmental conditions. PMID- 26546276 TI - A qualitative study of women's views on overdiagnosis and screening for thyroid cancer in Korea. AB - BACKGROUND: The incidence of thyroid cancer in Korea has increased by about 25 % every year for the past 10 years. This increase is largely due to a rising incidence in papillary thyroid cancer, which is associated with an overdiagnosis of small tumors that may never become clinically significant. This study was conducted to explore Korean women's understanding of overdiagnosis and to investigate changes in screening intention in response to overdiagnosis information. METHODS: Focus group interviews were conducted among women of ages 30-69 years, who are commonly targeted in Korea for cancer screening. Women were divided into four groups according to thyroid cancer screening history and history of thyroid disease. Of 51 women who were contacted, 29 (57 %) participated in the interviews. RESULTS: Prior awareness of thyroid cancer overdiagnosis was minimal. When informed about the risks of overdiagnosis, the participants were often surprised. Overcoming initial malcontent, many women remained skeptic about overdiagnosis and trusted in the advice of their physicians. Meanwhile, some of the study participants found explanations of overdiagnosis difficult to understand. Further, hearing about the risks of overdiagnosis had limited impact on the participants' attitudes and intentions to undergo thyroid cancer screening, as many women expressed willingness to undergoing continued screening in the future. CONCLUSION: A large majority of Korean women eligible for and had undergone thyroid cancer screening were unaware of the potential for overdiagnosis. Nevertheless, overdiagnosis information generally had little impact on their beliefs about thyroid cancer screening and their intentions to undergo future screening. Further research is needed to determine whether these findings could be generalized to the wider Korean population. PMID- 26546277 TI - Petroleum contaminated water and health symptoms: a cross-sectional pilot study in a rural Nigerian community. AB - BACKGROUND: The oil-rich Niger Delta suffers from extensive petroleum contamination. A pilot study was conducted in the region of Ogoniland where one community, Ogale, has drinking water wells highly contaminated with a refined oil product. In a 2011 study, the United Nations Environment Programme (UNEP) sampled Ogale drinking water wells and detected numerous petroleum hydrocarbons, including benzene at concentrations as much as 1800 times higher than the USEPA drinking water standard. UNEP recommended immediate provision of clean drinking water, medical surveillance, and a prospective cohort study. Although the Nigerian government has provided emergency drinking water, other UNEP recommendations have not been implemented. We aimed to (i) follow up on UNEP recommendations by investigating health symptoms associated with exposure to contaminated water; and (ii) assess the adequacy and utilization of the government-supplied emergency drinking water. METHODS: We recruited 200 participants from Ogale and a reference community, Eteo, and administered questionnaires to investigate water use, perceived water safety, and self reported health symptoms. RESULTS: Our multivariate regression analyses show statistically significant associations between exposure to Ogale drinking water and self-reported health symptoms consistent with petroleum exposure. Participants in Ogale more frequently reported health symptoms related to neurological effects (OR = 2.8), hematological effects (OR = 3.3), and irritation (OR = 2.7). CONCLUSIONS: Our results are the first from a community relying on drinking water with such extremely high concentrations of benzene and other hydrocarbons. The ongoing exposure and these pilot study results highlight the need for more refined investigation as recommended by UNEP. PMID- 26546279 TI - Towards Engineering Biological Systems in a Broader Context. AB - Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. PMID- 26546278 TI - Recent Advances in Deciphering the Structure and Molecular Mechanism of the AAA+ ATPase N-Ethylmaleimide-Sensitive Factor (NSF). AB - N-ethylmaleimide-sensitive factor (NSF), first discovered in 1988, is a key factor for eukaryotic trafficking, including protein and hormone secretion and neurotransmitter release. It is a member of the AAA+ family (ATPases associated with diverse cellular activities). NSF disassembles soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complexes in conjunction with soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP). Structural studies of NSF and its complex with SNAREs and SNAPs (known as 20S supercomplex) started about 20years ago. Crystal structures of individual N and D2 domains of NSF and low-resolution electron microscopy structures of full length NSF and 20S supercomplex have been reported over the years. Nevertheless, the molecular architecture of the 20S supercomplex and the molecular mechanism of NSF-mediated SNARE complex disassembly remained unclear until recently. Here we review recent atomic-resolution or near-atomic resolution structures of NSF and of the 20S supercomplex, as well as recent insights into the molecular mechanism and energy requirements of NSF. We also compare NSF with other known AAA+ family members. PMID- 26546280 TI - Association between anthropometric indices and cardiometabolic risk factors in pre-school children. AB - BACKGROUND: The world health organization (WHO) and the Identification and prevention of dietary- and lifestyle-induced health effects in children and infants- study (IDEFICS), released anthropometric reference values obtained from normal body weight children. This study examined the relationship between WHO [body mass index (BMI) and triceps- and subscapular-skinfolds], and IDEFICS (waist circumference, waist to height ratio and fat mass index) anthropometric indices with cardiometabolic risk factors in pre-school children ranging from normal body weight to obesity. METHODS: A cross-sectional study with 232 children (aged 4.1 +/- 0.05 years) was performed. Anthropometric measurements were collected and BMI, waist circumference, waist to height ratio, triceps- and subscapular-skinfolds sum and fat mass index were calculated. Fasting glucose, fasting insulin, homeostasis model analysis insulin resistance (HOMA-IR), blood lipids and apolipoprotein (Apo) B-100 (Apo B) and Apo A-I were determined. Pearson's correlation coefficient, multiple regression analysis and the receiver operating characteristic (ROC) curve analysis were run. RESULTS: 51% (n = 73) of the boys and 52% (n = 47) of the girls were of normal body weight, 49% (n = 69) of the boys and 48% (n = 43) of the girls were overweight or obese. Anthropometric indices correlated (p < 0.001) with insulin: [BMI (r = 0.514), waist circumference (r = 0.524), waist to height ratio (r = 0.304), triceps- and subscapular-skinfolds sum (r = 0.514) and fat mass index (r = 0.500)], and HOMA IR: [BMI (r = 0.509), waist circumference (r = 0.521), waist to height ratio (r = 0.296), triceps- and subscapular-skinfolds sum (r = 0.483) and fat mass index (r = 0.492)]. Similar results were obtained after adjusting by age and sex. The areas under the curve (AUC) to identify children with insulin resistance were significant (p < 0.001) and similar among anthropometric indices (AUC > 0.68 to AUC < 0.76). CONCLUSIONS: WHO and IDEFICS anthropometric indices correlated similarly with fasting insulin and HOMA-IR. The diagnostic accuracy of the anthropometric indices as a proxy to identify children with insulin resistance was similar. These data do not support the use of waist circumference, waist to height ratio, triceps- and subscapular- skinfolds sum or fat mass index, instead of the BMI as a proxy to identify pre-school children with insulin resistance, the most frequent alteration found in children ranging from normal body weight to obesity. PMID- 26546281 TI - Mechanisms of Toll-like Receptor 4 Endocytosis Reveal a Common Immune-Evasion Strategy Used by Pathogenic and Commensal Bacteria. AB - Microbe-induced receptor trafficking has emerged as an essential means to promote innate immune signal transduction. Upon detection of bacterial lipopolysaccharides (LPS), CD14 induces an inflammatory endocytosis pathway that delivers Toll-like receptor 4 (TLR4) to endosomes. Although several regulators of CD14-dependent TLR4 endocytosis have been identified, the cargo-selection mechanism during this process remains unknown. We reveal that, in contrast to classic cytosolic interactions that promoted the endocytosis of transmembrane receptors, TLR4 was selected as cargo for inflammatory endocytosis entirely through extracellular interactions. Mechanistically, the extracellular protein MD 2 bound to and dimerized TLR4 in order to promote this endocytic event. Our analysis of LPS variants from human pathogens and gut commensals revealed a common mechanism by which bacteria prevent inflammatory endocytosis. We suggest that evasion of CD14-dependent endocytosis is an attribute that transcends the concept of pathogenesis and might be a fundamental feature of bacteria that inhabit eukaryotic hosts. PMID- 26546283 TI - Five cancer drugs back on NHS list after deals with drug companies. PMID- 26546282 TI - Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance. AB - Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG coupled genotoxic activity in self-reactive immature B cells. PMID- 26546284 TI - Attention deficit hyperactivity disorder: From parents to children. AB - INTRODUCTION: Multiple studies of attention deficit hyperactivity disorder (ADHD) have recognised a heritability factor in that a higher frequency of the disorder is observed in children with an affected relative. Our aim was to determine the association between ADHD symptoms in young children enrolled in five schools in Bogota and a history of ADHD symptoms in their parents using the Wender-Utah Rating Scale. METHODOLOGY: Case-control study of participants selected according to DSM-IV criteria for ADHD and the Behavioral Assessment System for Children (BASC) completed by parents and teachers; the WISC-IV scale was used to exclude children with cognitive deficit. Parents completed the Wender-Utah Rating Scale to retrospectively identify any ADHD symptoms in childhood. A score of 36 was used as a cutoff point. RESULTS: The study included 202 children: 117 cases and 85 controls. A positive history of ADHD symptoms in childhood was identified for 16% of 175 mothers and 20.6% of 141 fathers. The presence of symptoms in either parent, especially the mother, constitutes a significant risk factor for ADHD in children and this relationship persists after controlling for different variables. If both parents have the disorder, the risk tends to increase. CONCLUSION: Although ADHD has been linked to a genetic component, other environmental factors may be involved in the disorder. PMID- 26546285 TI - Early- and late-onset Alzheimer disease: Are they the same entity? AB - Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. PMID- 26546286 TI - Educational differentials in disability vary across and within welfare regimes: a comparison of 26 European countries in 2009. AB - BACKGROUND: Social differentials in disability prevalence exist in all European countries, but their scale varies markedly. To improve understanding of this variation, the article focuses on each end of the social gradient. It compares the extent of the higher disability prevalence in low social groups (referred to as disability disadvantage) and of the lower prevalence in high social groups (disability advantage); country-specific advantages/disadvantages are discussed regarding the possible influence of welfare regimes. METHODS: Cross-sectional disability prevalence is measured by longstanding health-related activity limitation (AL) in the 2009 European Statistics on Income and Living Conditions (EU-SILC) across 26 countries classified into four welfare regime groups. Logistic models adjusted by country, age and sex (in all 30-79 years and in three age-bands) measured the country-specific ORs across education, representing the AL-disadvantage of low-educated and AL-advantage of high-educated groups relative to middle-educated groups. RESULTS: The relative AL-disadvantage of the low educated groups was small in Sweden (eg, 1.2 (1.0-1.4)), Finland, Romania, Bulgaria and Spain (youngest age-band), but was large in the Czech Republic (eg, 1.9 (1.7-2.2)), Denmark, Belgium, Italy and Hungary. The high-educated groups had a small relative AL-advantage in Denmark (eg, 0.9 (0.8-1.1)), but a large AL advantage in Lithuania (eg, 0.5 (0.4-0.6)), half of the Baltic and Eastern European countries, Norway and Germany (youngest age-band). There were notable differences within welfare regime groups. CONCLUSIONS: The country-specific disability advantages/disadvantages across educational groups identified here could help to identify determining factors and the efficiency of national policies implemented to tackle social differentials in health. PMID- 26546287 TI - Trust and health: testing the reverse causality hypothesis. AB - BACKGROUND: Social capital research has consistently shown positive associations between generalised trust and health outcomes over 2 decades. Longitudinal studies attempting to test causal relationships further support the theory that trust is an independent predictor of health. However, as the reverse causality hypothesis has yet to be empirically tested, a knowledge gap remains. The aim of this study, therefore, was to investigate if health status predicts trust. METHODS: Data employed in this study came from 4 waves of the British Household Panel Survey between years 2000 and 2007 (N=8114). The sample was stratified by baseline trust to investigate temporal relationships between prior self-rated health (SRH) and changes in trust. We used logistic regression models with random effects, as trust was expected to be more similar within the same individuals over time. RESULTS: From the 'Can trust at baseline' cohort, poor SRH at time (t 1) predicted low trust at time (t) (OR=1.38). Likewise, good health predicted high trust within the 'Cannot' trust cohort (OR=1.30). These patterns of positive association remained after robustness checks, which adjusted for misclassification of outcome (trust) status and the existence of other temporal pathways. CONCLUSIONS: This study offers empirical evidence to support the circular nature of trust/health relationship. The stability of association between prior health status and changes in trust over time differed between cohorts, hinting at the existence of complex pathways rather than a simple positive feedback loop. PMID- 26546288 TI - Dissecting ventricular pseudoaneurysm after perimyocarditis-a case report. AB - BACKGROUND: The current case describes the fast development of a pseudoaneurysm in a patient that presented with signs of systemic inflammation and generally deranged blood work. CASE PRESENTATION: The pseudoaneurysm appeared within one week of disease onset. The anatomic extent of the pseudoaneurysm was unusual, as it dissected intramurally beneath the septum, inferior to the right ventricle and had effect on the RV filling. The etiology could not be definitely defined, since in adults the most common cause for pseudoaneurysm development is recent myocardial infarction, but in this patient the coronary arteries were healthy. Instead it could have been a consequence of an aggressive perimyocarditis. CONCLUSIONS: Due to the unpredictable nature of pseudoaneurysms we advocate early contact with a center with cardiothoracic surgery expertise for rapid surgical intervention. PMID- 26546289 TI - Genetic diversity of the Korean field strains of porcine reproductive and respiratory syndrome virus. AB - Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically significant diseases in the swine industry. The PRRS virus (PRRSV) has genetically diverse populations, like other RNA viruses, and various field strains continue to be reported worldwide. The molecular epidemiological study of PRRSV can provide important data for use in controlling the disease. In this study, 50 oral fluid samples from conventional farms in Korea were taken to analyze nucleotide sequences of the open reading frame 5 of PRRSV. The viruses present in more than 80% of oral fluid samples genetically originated from the type 2 PRRSV, which is North American (NA) lineage. In addition 8.9% of samples contained both of the type 1 PRRSV, which is European (EU) lineage and the type 2 PRRSV. About 60% of farms involved in this study had more than two strains of PRRSV. In phylogenetic analysis, the Korean field strains of PRRSV detected from the oral fluid samples were divided into several subgroups: four subgroups of Korean field strains clustered with the type 1 PRRSV, and other five subgroups of Korean field strains clustered with the type 2. These results suggest that the type 2 PRRSV is more prevalent than the type 1 in Korea and heterologous strains of PRRSV can simultaneously infect a single pig farm. PMID- 26546290 TI - Bone fractures and lumbar mineral density after renal transplantation. A long term cross-sectional study. AB - BACKGROUND: The purpose of this work was to investigate the association of vertebral and peripheral fractures 10 yr after grafting with bone metabolic markers and body mass density (BMD). PATIENTS AND METHODS: One hundred thirty eight recipients with stable graft function were included in a cross-sectional study. Graft function, biochemical mineral metabolism markers and body mass density (DEXA) were measured. Vertebral fractures were assessed by a semiquantitative analysis of lateral spine X-ray exam. RESULTS: At the time of the study, intact parathyroid hormone levels were 127.5 +/- 78.4 pg/mL and serum calcidiol 20.4 +/- 9.3 ng/mL. DEXA showed osteopenia in 47% and osteoporosis in 23% at lumbar spine, 51% and 14% at femoral neck, and 53% and 8% at trochanter. Eighty-five recipients presented vertebral fractures, 69 mild and 16 moderate/severe fractures. In the multivariate analysis, vertebral fractures were associated with older age (p = 0.010), length of follow-up (p = 0.022) and trochanter T-score (p = 0.038). Twenty-three patients presented peripheral fractures and 19 of them also had vertebral fractures. Patients with peripheral fractures were younger, mostly women and had lower BMD. CONCLUSIONS: Vertebral fractures were associated with lower BMD at trochanter. Most fractures were mild and were several times more frequent than in general population. Their clinical significance needs to be determined. PMID- 26546291 TI - MDCT features of hepatocellular carcinoma (HCC) in non-cirrhotic liver. AB - PURPOSE: To describe the multidetector row computed tomography (MDCT) imaging features of HCC that develops in patients who are free from underlying liver cirrhosis and to determine if the MDCT presentation of this specific tumor differs from that of the more common HCC that develops in patients with liver cirrhosis using a retrospective case-control study. PATIENTS AND METHODS: The MDCT examinations of 38 patients with HCC in non-cirrhotic liver (group 1) were quantitatively and qualitatively analyzed and compared to those obtained in 38 patients with HCC in cirrhotic liver (group 2) matched for age and gender. Quantitative and qualitative characteristics of HCC of both groups were compared using univariate analysis. RESULTS: HCCs were significantly larger in group 1 (81.5mm+/-55.5) than in group 2 (44.5mm+/-39.1 SD; P=0.0015). In group 1, HCCs were more frequently single tumors (87%) than in group 2 (37%) (P<0.0001), encapsulated (92% vs. 47% respectively; P<0.0001), had more frequently fatty component (24% vs. 8%, respectively; P=0.0279) and internal hemorrhage (29% vs. 3%, respectively; P=0.0033). No significant differences were found between the two groups for location, hyperenhancement of HCC during the arterial phase, washout during the portal phase, endoluminal portal involvement by HCC, endoportal cruoric thrombus, invasion of adjacent organs and underlying liver steatosis. CONCLUSION: HCC in non-cirrhotic liver are larger than those observed in cirrhotic liver and more frequently present as a single encapsulated tumor. They have the same patterns of enhancement than HCC that develops in cirrhotic liver. PMID- 26546292 TI - TOR Complexes and the Maintenance of Cellular Homeostasis. AB - The Target of Rapamycin (TOR) is a conserved serine/threonine (ser/thr) kinase that functions in two, distinct, multiprotein complexes called TORC1 and TORC2. Each complex regulates different aspects of eukaryote growth: TORC1 regulates cell volume and/or mass by influencing protein synthesis and turnover, while TORC2, as detailed in this review, regulates cell surface area by influencing lipid production and intracellular turgor. TOR complexes function in feedback loops, implying that downstream effectors are also likely to be involved in upstream regulation. In this regard, the notion that TORCs function primarily as mediators of cellular and organismal homeostasis is fundamentally different from the current, predominate view of TOR as a direct transducer of extracellular biotic and abiotic signals. PMID- 26546293 TI - Super-Resolution Microscopy: From Single Molecules to Supramolecular Assemblies. AB - Super-resolution microscopy (SRM) methods have allowed scientists to exceed the diffraction limit of light, enabling the discovery and investigation of cellular structures at the nanometer scale, from individual proteins to entire organelles. In this review we survey the application of SRM in elucidating the structure of macromolecules in the native cellular environment. We emphasize how SRM can generate molecular maps of protein complexes and extract quantitative information on the number, size, distribution, and spatial organization of macromolecules. We discuss both the novel information that can be generated through SRM as well as the experimental considerations to examine while conducting such studies. With the increasing popularity of SRM in the biological sciences, this review will serve as a tool to navigate the range of applications and harness the power of SRM to elucidate biological structures. PMID- 26546294 TI - Phylogenetic and morphological characterization of trypanosomes from Brazilian armoured catfishes and leeches reveal high species diversity, mixed infections and a new fish trypanosome species. AB - BACKGROUND: Several Trypanosoma species transmitted by leeches infect marine and freshwater fish worldwide. To date, all South American fish trypanosome species identified have been based on unreliable morphological parameters. We recently isolated and cultured trypanosomes from the Brazilian armoured catfishes Hypostomus luetkeni and H. affinis. Here, we report the first phylogenetic analyses of South American (Brazilian) trypanosomes isolated from fish, and from leeches removed from these fish. We also analysed morphologically and morphometrically the different forms of fish, leech and cultured trypanosomes. METHODS: V7V8 SSU rRNA and gGAPDH sequences were used for phylogenetic analysis of Brazilian fish and leech trypanosomes. Trypanosomes from cultures, fish blood and leech samples were also characterized morphologically and morphometrically by light and electron microscopy. RESULTS: In blood smears from fish high trypanosome prevalence (90-100 %) and parasitemia (0.9-1.0x10(2)) were observed. Phylogenetic relationships using SSU rRNA and gGAPDH showed that, despite relevant sequence divergence, all Brazilian fish (and derived cultures) and leech trypanosomes clustered together into a single clade. The Brazilian clade clustered with European, North American and African fish trypanosomes. Based on sequence analysis, we uncovered a new species of Brazilian fish trypanosome, Trypanosoma abeli n. sp. Trypanosoma abeli cultures contained pleomorphic epimastigotes, small trypomastigotes and rare sphaeromastigotes. Ultrastructural features of T. abeli included a cytostome-cytopharynx complex in epi- and trypomastigotes, a compact rod-like kinetoplast, lysosome-related organelles (LROs) and multivesicular bodies. Trypanosomes found in fish blood smears and leech samples were highly pleomorphic, in agreement with sequence data suggesting that catfishes and leeches often have mixed trypanosome infections. CONCLUSIONS: Trypanosoma abeli n. sp. is the first trypanosome from South American fishes isolated in culture, positioned in phylogenetic trees and characterized at the ultrastructural level. Trypanosoma abeli n. sp. is highly prevalent in H. luetkeni and H. affinis armoured catfish from the Atlantic Forest biome, and in other catfish species from the Amazon and the Pantanal. Sequencing data suggested that Brazilian catfish often have mixed trypanosome infections, highlighting the importance of molecular characterization to identify trypanosome species in fishes and leeches. PMID- 26546295 TI - Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer. AB - Entrectinib is a first-in-class pan-TRK kinase inhibitor currently undergoing clinical testing in colorectal cancer and other tumor types. A patient with metastatic colorectal cancer harboring an LMNA-NTRK1 rearrangement displayed a remarkable response to treatment with entrectinib, which was followed by the emergence of resistance. To characterize the molecular bases of the patient's relapse, circulating tumor DNA (ctDNA) was collected longitudinally during treatment, and a tissue biopsy, obtained before entrectinib treatment, was transplanted in mice (xenopatient), which then received the same entrectinib regimen until resistance developed. Genetic profiling of ctDNA and xenopatient samples showed acquisition of two point mutations in the catalytic domain of NTRK1, p.G595R and p.G667C. Biochemical and pharmacologic analysis in multiple preclinical models confirmed that either mutation renders the TRKA kinase insensitive to entrectinib. These findings can be immediately exploited to design next-generation TRKA inhibitors. SIGNIFICANCE: We provide proof of principle that analyses of xenopatients (avatar) and liquid biopsies allow the identification of drug resistance mechanisms in parallel with clinical treatment of an individual patient. We describe for the first time that p.G595R and p.G667C TRKA mutations drive acquired resistance to entrectinib in colorectal cancers carrying NTRK1 rearrangements. PMID- 26546297 TI - Huge Data-Sharing Project Launched. AB - Aiming to advance precision medicine in oncology and improve patient care, the American Association for Cancer Research has launched an international initiative known as AACR Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE). The venture will pool existing and future next-generation clinical sequencing data with longitudinal clinical outcomes and related pathology reports from several institutions in the United States, Canada, and Europe, to find new mutations, assess potential biomarkers, and identify patient populations that might benefit from existing treatments. PMID- 26546296 TI - MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy. AB - An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in a region of the X chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy-number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRAS(G12C)-addicted cell line after KRAS downregulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action. SIGNIFICANCE: MECP2 is a commonly amplified oncogene in human malignancies with a unique epigenetic mechanism of action. Cancer Discov; 6(1); 45-58. (c)2015 AACR.This article is highlighted in the In This Issue feature, p. 1. PMID- 26546299 TI - The Art of the Diagnostic Report. PMID- 26546298 TI - Hysteroscopic local anesthetic intrauterine cornual block in office endometrial ablation: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy of a hysteroscopic local anesthetic intrauterine cornual block (ICOB) on pain experienced during office endometrial ablation (EA) in addition to a traditional direct local anesthetic cervical block (DCB). DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: University teaching hospital. PATIENT(S): Women with heavy menstrual bleeding scheduled for an office endometrial ablation. INTERVENTION(S): Before office EA, DCB plus hysteroscopic ICOB just medial to each tubal ostium using local anesthetic mixture made up of 1 mL 3% mepivacaine plus 1 mL 0.5% bupivacaine versus control group receiving DBC plus ICOB with 2 mL of placebo (saline). MAIN OUTCOME MEASURE(S): PRIMARY OUTCOME: pain reported during procedure via visual analogue scale (VAS) from 0 to 10; secondary outcomes: postoperative pain, rescue analgesic requirement, and duration of hospital stay. RESULT(S): Most characteristics were similar across groups. The mean VAS score during the procedure was statistically significantly lower by 1.44 (95% confidence interval, -2.65 to -0.21) in the active group compared with the placebo group. There were no statistically significant differences between the two groups in the postprocedural mean VAS scores, rescue analgesic requirement, or duration of hospital stay. CONCLUSION(S): Used in addition to DCB, ICOB reduces the pain experienced during office EA compared with DCB alone. CLINICAL TRIAL REGISTRATION NUMBER: NCT01808898. PMID- 26546300 TI - Vertebral Augmentation After Recent Randomized Controlled Trials: A New Rise in Kyphoplasty Volumes. AB - PURPOSE: In 2009, the results of two randomized controlled trials refuting the effectiveness of vertebroplasty compared with sham procedures were published in a leading journal. The purpose of the present study was to evaluate the impact of these randomized trials on subsequent volume and utilization rates of vertebral augmentation (VA) in the United States. METHODS: Using nationwide Medicare Part B databases, Current Procedural Terminology, version 4, codes for thoracic and lumbar vertebroplasty and kyphoplasty were studied from 2006 to 2013 (codes 22520 to 22525). The total volumes of procedures were determined and utilization rates were calculated. Volumes and rates by provider specialty were also studied. RESULTS: The total volume of VA procedures peaked in 2008 at 101,807 and thereafter fell steadily to 80,940 in 2013. The utilization rates per 100,000 beneficiaries also showed a similar trend. Radiologists performed the largest number of VA procedures in 2013 (33,618 procedures [42%]), followed by orthopedic surgeons (19,886 procedures [25%]). After 2009, vertebroplasty volumes decreased sharply. Kyphoplasty volumes increased in 2011, after an initial decrease in 2010. The divergent trend in the volumes of the two procedures persisted through 2013. CONCLUSIONS: After the publication of the two trials' results in 2009, vertebroplasty volumes and rates decreased sharply. However, there is an emerging trend toward performing more kyphoplasty procedures, mitigating the decrease in total volume of VA procedures. Radiologists have the strongest role in performing these procedures among all medical specialties. PMID- 26546301 TI - Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model. AB - BACKGROUND: Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. HYPOTHESIS: Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. STUDY DESIGN: Controlled laboratory study. METHODS: Standardized rectangular (4 * 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. RESULTS: Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P < .023). Application of 1.0-mm microfracture awls led to a significantly improved histological overall repair tissue quality (7.02 +/- 0.70 vs 9.03 +/- 0.69; P = .008) and surface grading (1.05 +/- 0.28 vs 2.10 +/- 0.19; P = .001) compared with larger awls. The small-diameter awl decreased relative bone volume of the subarticular spongiosa (bone volume/tissue volume ratio: 23.81% +/- 3.37% vs 30.58% +/- 2.46%; P = .011). Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. CONCLUSION: Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. CLINICAL RELEVANCE: These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. PMID- 26546302 TI - Sex Differences in Self-Reported Hip Function Up to 2 Years After Arthroscopic Surgery for Femoroacetabular Impingement. AB - BACKGROUND: Femoroacetabular impingement (FAI) is a significant cause of disability in young adults. Hip arthroscopic surgery restores bony congruence and improves function in the majority of patients, but recent evidence indicates that women may experience worse pre- and postoperative function than men. PURPOSE/HYPOTHESIS: The purpose of this study was to identify whether self reported hip function differed between men and women with symptomatic FAI. The hypothesis was that mean self-reported hip function scores would improve after arthroscopic surgery but that women would report poorer function than men both before and up to 2 years after arthroscopic surgery. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 229 patients (68.4% women; mean [+/-SD] age, 31.6 +/- 10.8 years; mean [+/-SD] body mass index, 26.8 +/- 11.9 kg/m(2)) underwent hip arthroscopic surgery for unilateral symptomatic FAI. All eligible and consenting patients with radiologically and clinically confirmed FAI completed the International Hip Outcome Tool (iHOT-33) and the Hip Outcome Score activities of daily living subscale (HOS-ADL) before hip arthroscopic surgery and at 3, 6, 12, and 24 months after arthroscopic surgery. A linear mixed model for repeated measures was used to test for differences in self-reported hip function between men and women over the study period (P <= .05). RESULTS: There were no significant time * sex interactions for either the HOS-ADL (P = .12) or iHOT-33 (P = .64), but both measures showed significant improvements between the preoperative time point and each of the 4 follow-up points (P < .0001); however, self-reported hip function did not improve between 6 and 24 months after arthroscopic surgery (P >= .11). Post hoc independent t tests indicated that women reported poorer hip function than did men before surgery (P <= .003) both on the HOS-ADL (mean +/- standard error of the mean [SEM], 67.4 +/- 1.9 [men] vs 60.5 +/- 1.3 [women]) and iHOT-33 (mean +/- SEM, 38.0 +/- 1.9 [men] vs 30.9 +/- 1.3 [women]); scores were not different between sexes at any other time point. CONCLUSION: These findings indicate improvements in self-reported hip function in patients with FAI, regardless of sex, until 6 months after hip arthroscopic surgery. Although women reported poorer preoperative function than did men, the differences were not significant 2 years after surgery. PMID- 26546303 TI - Epidemiology of Elbow Dislocations in High School Athletes. AB - BACKGROUND: The elbow is the second most commonly dislocated major joint in the general population. Previous studies that focused on emergency department populations indicate that such injuries occur most frequently among adolescent athletes. PURPOSE: To describe the epidemiological rates and patterns of sports related elbow dislocations in high school athletes. STUDY DESIGN: Descriptive epidemiology study. METHODS: Sports-related injury data for the 2005-2006 through 2013-2014 academic years from a national convenience sample of high schools participating in the National High School Sports-Related Injury Surveillance Study (High School Reporting Information Online [RIO]) were analyzed. RESULTS: Certified athletic trainers participating in High School RIO reported 115 of 1246 (9.2%) elbow injuries as elbow dislocations. A total of 30,415,179 athlete exposures (AEs) were reported during the study period, resulting in a dislocation rate of 0.38 per 100,000 AEs. The majority of the dislocations resulted from boys' wrestling (46.1%) and football (37.4%). Elbow dislocation rates were higher in competition than in practice. Also, 91.3% of dislocations occurred in boys' sports. Among both boys (60.4%) and girls (88.9%), the majority of injuries occurred during varsity sports activities. Contact with another person was the most common injury mechanism (46.9%), followed by contact with the playing surface (46.0%). Dislocations more commonly resulted in removal from play for more than 3 weeks (23.4% vs 6.9%, respectively) or medical disqualification (36.9% vs 7.0%, respectively) compared with other elbow injuries. Dislocations were also more likely to result in surgical treatment than other elbow injuries (13.6% vs 4.7%, respectively). CONCLUSION: In high school athletes, elbow dislocations result in longer removal from play and are more likely to require surgical treatment than nondislocation-associated elbow injuries. Rates and patterns of elbow dislocations vary by sport. In high-risk sports, focused sport specific prevention strategies may help to decrease the rates and severity of elbow dislocation injuries. PMID- 26546304 TI - Epidemiology of Sports-Related Concussions in National Collegiate Athletic Association Athletes From 2009-2010 to 2013-2014: Symptom Prevalence, Symptom Resolution Time, and Return-to-Play Time. AB - BACKGROUND: Limited data exist among collegiate student-athletes on the epidemiology of sports-related concussion (SRC) outcomes, such as symptoms, symptom resolution time, and return-to-play time. PURPOSE: This study used the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) to describe the epidemiology of SRC outcomes in 25 collegiate sports. STUDY DESIGN: Descriptive epidemiology study. METHODS: SRC data from the NCAA ISP during the 2009-2010 to 2013-2014 academic years were analyzed regarding symptoms, time to resolution of symptoms, and time to return to play. Findings were also stratified by sex in sex-comparable sports (ie, ice hockey, soccer, basketball, lacrosse, baseball/softball) and whether SRCs were reported as recurrent. RESULTS: Of the 1670 concussions reported during the 2009-2010 to 2013 2014 academic years, an average (+/-SD) of 5.29 +/- 2.94 concussion symptoms were reported, with the most common being headache (92.2%) and dizziness (68.9%). Most concussions had symptoms resolve within 1 week (60.1%); however, 6.2% had a symptom resolution time of over 4 weeks. Additionally, 8.9% of concussions required over 4 weeks before return to play. The proportion of SRCs that required at least 1 week before return to play increased from 42.7% in 2009-2010 to 70.2% in 2013-2014 (linear trend, P < .001). Within sex-comparable sports analyses, the average number of symptoms and symptom resolution time did not differ by sex. However, a larger proportion of concussions in male athletes included amnesia and disorientation; a larger proportion of concussions in female athletes included headache, excess drowsiness, and nausea/vomiting. A total of 151 SRCs (9.0%) were reported as recurrent. The average number of symptoms reported with recurrent SRCs (5.99 +/- 3.43) was greater than that of nonrecurrent SRCs (5.22 +/- 2.88; P = .01). A greater proportion of recurrent SRCs also resulted in a long symptom resolution time (14.6% vs 5.4%, respectively; P < .001) and long return-to-play time (21.2% vs 7.7%, respectively; P < .001) compared with nonrecurrent SRCs. CONCLUSION: Trends in return-to-play time may indicate changing concussion management practices in which team medical staff members withhold players from participation longer to ensure symptom resolution. Concussion symptoms may differ by sex and recurrence. Future research should continue to examine the trends and discrepancies in symptom resolution time and return-to-play time. PMID- 26546305 TI - User Perceptions and Reactions to an Online Cancer Risk Assessment Tool: a Process Evaluation of Cancer Risk Check. AB - Online cancer risk assessment tools, which provide personalized cancer information and recommendations based on personal data input by users, are a promising cancer education approach; however, few tools have been evaluated. A randomized controlled study was conducted to compare user impressions of one tool, Cancer Risk Check (CRC), to non-personalized educational information delivered online as series of self-advancing slides (the control). CRC users (N = 1452) rated the tool to be as interesting as the control (p > .05), but users were more likely to report that the information was difficult to understand and not applicable to them (p < .05). Information seeking and sharing also were lower among CRC users; thus, although impressions of CRC were favorable, it was not shown to be superior to existing approaches. We hypothesized CRC was less effective because it contained few visual and graphical elements; therefore, CRC was compared to a text-based control (online PDF file) post hoc. CRC users rated the information to be more interesting, less difficult to understand, and better able to hold their attention (p < .05). Post hoc results suggest the visual presentation of risk is critical to tool success. PMID- 26546306 TI - Use of antiarrhythmic drugs during ablation of persistent atrial fibrillation: observations from a large single-centre cohort. AB - Catheter ablation of complex fractionated atrial electrograms (CFAE), also known as defragmentation ablation, may be considered for the treatment of persistent atrial fibrillation (AF) beyond pulmonary vein isolation (PVI). Concomitant antiarrhythmic drug (AAD) therapy is common, but the relevance of AAD administration and its optimal timing during ablation remain unclear. Therefore, we investigated the use and timing of AADs during defragmentation ablation and their possible implications for AF termination and ablation success in a large cohort of patients. Retrospectively, we included 200 consecutive patients (age: 61 +/- 12 years, LA diameter: 47 +/- 8 mm) with persistent AF (episode duration 47 +/- 72 weeks) who underwent de novo ablation including CFAE ablation. In all patients, PVI was performed prior to CFAE ablation. The use and timing of AADs were registered. The follow-ups consisted of Holter ECGs and clinical visits. Termination of AF was achieved in 132 patients (66 %). Intraprocedural AADs were administered in 168/200 patients (84 %) 45 +/- 27 min after completion of PVI. Amiodarone was used in the majority of the patients (160/168). The timing of AAD administration was predicted by the atrial fibrillation cycle length (AFCL). At follow-up, 88 patients (46 %) were free from atrial arrhythmia. Multivariate logistic regression analysis revealed that administration of AAD early after PVI, LA size, duration of AF history, sex and AFCL were predictors of AF termination. The administration of AAD and its timing were not predictive of outcome, and age was the sole independent predictor of AF recurrence. The administration of AAD during ablation was common in this large cohort of persistent AF patients. The choice to administer AAD therapy and the timing of the administration during ablation were influenced by AFCL, and these factors did not significantly influence the moderate single procedure success rate in this retrospective analysis. PMID- 26546307 TI - Cloning and characterization of the gene for L-amino acid oxidase in hybrid tilapia. AB - Tilapia is the common name for a group of cichlid fishes. Identification of DNA markers significantly associated with important traits in candidate genes may speed up genetic improvement. L-Amino acid oxidase (LAO) plays a crucial role in the innate immune defences of animals. Previously, whether LAO variants were associated with economic traits had not been studied in fish. We characterized the cDNA sequence of the LAO gene of hybrid tilapia (Oreochromis spp.). Its ORF was 1536 bp, encoding a flavoenzyme of 511 amino acids. This gene consisted of seven exons and six introns. Its expression was detected in the intestine, blood, kidney, skin, liver. It was highly expressed in the intestine. After a challenge with a bacterial pathogen, Streptococcus agalactiae, its expression was up regulated significantly in the liver, intestine and spleen (P < 0.05). We identified one SNP in the genomic sequence of the gene and found that this SNP was associated significantly with body length (P < 0.05), but not with resistance to S. agalactiae. The results of this study suggest that the LAO gene plays an important role in innate immune responses to the bacterial pathogen in tilapia. The investigation of relationship between polymorphism of LAO gene and disease resistance and growth in tilapia showed that one SNP was associated significantly with body length. Further experiments on whether SNPs in the LAO gene are associated with growth in tilapia and other populations could be useful in understanding more functions of the LAO gene. PMID- 26546309 TI - Using Ancient Samples in Projection Analysis. AB - Projection analysis is a tool that extracts information from the joint allele frequency spectrum to better understand the relationship between two populations. In projection analysis, a test genome is compared to a set of genomes from a reference population. The projection's shape depends on the historical relationship of the test genome's population to the reference population. Here, we explore in greater depth the effects on the projection when ancient samples are included in the analysis. First, we conduct a series of simulations in which the ancient sample is directly ancestral to a present-day population (one population model), or the ancient sample is ancestral to a sister population that diverged before the time of sampling (two-population model). We find that there are characteristic differences between the projections for the one-population and two-population models, which indicate that the projection can be used to determine whether a test genome is directly ancestral to a present-day population or not. Second, we compute projections for several published ancient genomes. We compare two Neanderthals and three ancient human genomes to European, Han Chinese and Yoruba reference panels. We use a previously constructed demographic model and insert these five ancient genomes to assess how well the observed projections are recovered. PMID- 26546308 TI - The Genomic Signature of Population Reconnection Following Isolation: From Theory to HIV. AB - Ease of worldwide travel provides increased opportunities for organisms not only to colonize new environments but also to encounter related but diverged populations. Such events of reconnection and secondary contact of previously isolated populations are widely observed at different time scales. For example, during the quaternary glaciation, sea water level fluctuations caused temporal isolation of populations, often to be followed by secondary contact. At shorter time scales, population isolation and reconnection of viruses are commonly observed, and such events are often associated with epidemics and pandemics. Here, using coalescent theory and simulations, we describe the temporal impact of population reconnection after isolation on nucleotide differences and the site frequency spectrum, as well as common summary statistics of DNA variation. We identify robust genomic signatures of population reconnection after isolation. We utilize our development to infer the recent evolutionary history of human immunodeficiency virus 1 (HIV-1) in Asia and South America, successfully retrieving the successive HIV subtype colonization events in these regions. Our analysis reveals that divergent HIV-1 subtype populations are currently admixing in these regions, suggesting that HIV-1 may be undergoing a process of homogenization, contrary to popular belief. PMID- 26546311 TI - The development of the Hong Kong Heat Index for enhancing the heat stress information service of the Hong Kong Observatory. AB - This paper presents a study to develop a heat index, for use in hot and humid sub tropical climate in Hong Kong. The study made use of hospitalization data and heat stress measurement data in Hong Kong from 2007 to 2011. The heat index, which is called Hong Kong Heat Index (HKHI), is calculated from the natural wet bulb temperature, the globe temperature, and the dry bulb temperature together with a set of coefficients applicable to the high humidity condition in the summer of Hong Kong. Analysis of the response of hospitalization rate to variation in HKHI and two other heat indices, namely Wet Bulb Globe Temperature (WBGT) and Net Effective Temperature (NET), revealed that HKHI performed generally better than WBGT and NET in reflecting the heat stress impact on excess hospitalization ratio in Hong Kong. Based on the study results, two reference criteria of HKHI were identified to establish a two-tier approach for the enhancement of the heat stress information service in Hong Kong. PMID- 26546310 TI - Disruption of Methionine Metabolism in Drosophila melanogaster Impacts Histone Methylation and Results in Loss of Viability. AB - Histone methylation levels, which are determined by the action of both histone demethylases and methyltransferases, impact multiple biological processes by affecting gene expression activity. Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. The functions of methionine metabolic enzymes in regulating biological processes as well as the interaction between the methionine pathway and histone methylation, however, are still not fully understood. Here, we report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone methylation levels. Reduction of little imaginal discs (LID) histone demethylase, but not lysine-specific demethylase 2 (KDM2) demethylase, is able to counter the effects on histone methylation due to reduction of SAM synthetase (SAM-S). Taken together, these results reveal an essential role of key enzymes that control methionine metabolism and histone methylation. Additionally, these findings are an indication of a strong connection between metabolism and epigenetics. PMID- 26546312 TI - Weather conditions and their effect on the increase of the risk of type A acute aortic dissection onset in Berlin. AB - In this study, a minimum distance classification and forward feature selection technique are joined to determine the relationship between weather conditions and the increase of the risk of type A acute aortic dissection (AAD) events in Berlin. The results demonstrate that changes in the amount of cloudiness and air temperature are the most representative weather predictors among the studied parameters. A discrimination surface was developed for the prediction of AAD events 6 h ahead, and it is found that, under a specific amount of cloudiness and air temperature, the risk of AAD events in Berlin increases about 20 %. PMID- 26546314 TI - Reply to comments on papers by Lu et al. PMID- 26546313 TI - Could both vitamin D and geomagnetic activity impact serum levels of soluble cell adhesion molecules in young men? AB - Vitamin D might have a role in diminishing endothelial dysfunction (ED). The initial aim was to test the hypothesis of reciprocity between levels of 25 hydroxyvitamin D (25(OH)D) and levels of soluble endothelial cell adhesion molecules (CAMs) that could serve as biomarkers of ED. Randomly selected men of age 20-39 were examined at February or March (cold season) and reexamined at August or September (warm season). Some lifestyle and anthropometrical data were recorded. Laboratory measurements, including those for serum levels of soluble CAMs-sICAM-1, sVCAM-1, sE-selectin and sP-selectin-were also performed. As some of the results were rather unexpected, indices of geomagnetic activity (GMA), obtained from the online database, were included in further analysis as a confounder. In 2012-2013, 130 men were examined in cold season, and 125 of them were reexamined in warm season. 25(OH)D levels were found to be significantly negatively associated with sVCAM-1 levels (beta = -0.15, p = 0.043 in warm season; beta = -0.19, p = 0.007 for changes). Levels of sVCAM-1 and sICAM-1 from the same seasons were notably different between years and have changed in an opposite manner. Soluble P-selectin levels were higher at warm season in both years. GMA was positively associated with sVCAM-1 (beta = 0.17, p = 0.039 in cold season; beta = 0.22, p = 0.002 for changes) and negatively with sICAM-1 (beta = 0.30. p < 0.001 in cold season) levels. Vitamin D might play a role in diminishing sVCAM-1 levels. Levels of sVCAM-1 and sICAM-1 were associated with the GMA; this implies a need for further research. PMID- 26546315 TI - Fatal Psychrobacter sp. infection in a pediatric patient with meningitis identified by metagenomic next-generation sequencing in cerebrospinal fluid. AB - The genus Psychrobacter contains environmental, psychrophilic and halotolerant gram-negative bacteria considered rare opportunistic pathogens in humans. Metagenomics was performed on the cerebrospinal fluid (CSF) of a pediatric patient with meningitis. Nucleic acids were extracted, randomly amplified, and sequenced with the 454 GS FLX Titanium next-generation sequencing (NGS) system. Sequencing reads were assembled, and potential virulence genes were predicted. Phylogenomic and phylogenetic studies were performed. Psychrobacter sp. 310 was identified, and several virulence genes characteristic of pathogenic bacteria were found. The phylogenomic study and 16S rRNA gene phylogenetic analysis showed that the closest relative of Psychrobacter sp. 310 was Psychrobacter sanguinis. To our knowledge, this is the first report of a meningitis case associated with Psychrobacter sp. identified by NGS metagenomics in CSF from a pediatric patient. The metagenomic strategy based on NGS was a powerful tool to identify a rare unknown pathogen in a clinical case. PMID- 26546316 TI - Transcriptional analysis of exopolysaccharides biosynthesis gene clusters in Lactobacillus plantarum. AB - Exopolysaccharides (EPS) from lactic acid bacteria contribute to specific rheology and texture of fermented milk products and find applications also in non dairy foods and in therapeutics. Recently, four clusters of genes (cps) associated with surface polysaccharide production have been identified in Lactobacillus plantarum WCFS1, a probiotic and food-associated lactobacillus. These clusters are involved in cell surface architecture and probably in release and/or exposure of immunomodulating bacterial molecules. Here we show a transcriptional analysis of these clusters. Indeed, RT-PCR experiments revealed that the cps loci are organized in five operons. Moreover, by reverse transcription-qPCR analysis performed on L. plantarum WCFS1 (wild type) and WCFS1 2 (DeltaccpA), we demonstrated that expression of three cps clusters is under the control of the global regulator CcpA. These results, together with the identification of putative CcpA target sequences (catabolite responsive element CRE) in the regulatory region of four out of five transcriptional units, strongly suggest for the first time a role of the master regulator CcpA in EPS gene transcription among lactobacilli. PMID- 26546317 TI - Cytomegalovirus Encephalitis in a Patient with Severe Combined Immunodeficiency. PMID- 26546319 TI - Overexpression of a Phytophthora Cytoplasmic CRN Effector Confers Resistance to Disease, Salinity and Drought in Nicotiana benthamiana. AB - The Crinkler (CRN) effector family is produced by oomycete pathogens and may manipulate host physiological and biochemical events inside host cells. Here, PsCRN161 was identified from Phytophthora sojae based on its broad and strong cell death suppression activities. The effector protein contains two predicted nuclear localization signals and localized to nuclei of plant cells, indicating that it may target plant nuclei to modify host cell physiology and function. The chimeric gene GFP:PsCRN161 driven by the Cauliflower mosaic virus (CaMV) 35S promoter was introduced into Nicotiana benthamiana. The four independent PsCRN161 transgenic lines exhibited increased resistance to two oomycete pathogens (P. parasitica and P. capsici) and showed enhanced tolerance to salinity and drought stresses. Digital gene expression profiling analysis showed that defense-related genes, including ABC transporters, Cyt P450 and receptor-like kinases (RLKs), were significantly up-regulated in PsCRN161-transgenic plants compared with GFP (green fluorescent protein) lines, implying that PsCRN161 expression may protect plants from biotic and abiotic stresses by up-regulation of many defense-related genes. The results reveal previously unknown functions of the oomycete effectors, suggesting that the pathogen effectors could be directly used as functional genes for plant molecular breeding for enhancement of tolerance to biotic and abiotic stresses. PMID- 26546318 TI - ATTED-II in 2016: A Plant Coexpression Database Towards Lineage-Specific Coexpression. AB - ATTED-II (http://atted.jp) is a coexpression database for plant species with parallel views of multiple coexpression data sets and network analysis tools. The user can efficiently find functional gene relationships and design experiments to identify gene functions by reverse genetics and general molecular biology techniques. Here, we report updates to ATTED-II (version 8.0), including new and updated coexpression data and analysis tools. ATTED-II now includes eight microarray- and six RNA sequencing-based coexpression data sets for seven dicot species (Arabidopsis, field mustard, soybean, barrel medick, poplar, tomato and grape) and two monocot species (rice and maize). Stand-alone coexpression analyses tend to have low reliability. Therefore, examining evolutionarily conserved coexpression is a more effective approach from the viewpoints of reliability and evolutionary importance. In contrast, the reliability of species specific coexpression data remains poor. Our assessment scores for individual coexpression data sets indicated that the quality of the new coexpression data sets in ATTED-II is higher than for any previous coexpression data set. In addition, five species (Arabidopsis, soybean, tomato, rice and maize) in ATTED-II are now supported by both microarray- and RNA sequencing-based coexpression data, which has increased the reliability. Consequently, ATTED-II can now provide lineage-specific coexpression information. As an example of the use of ATTED-II to explore lineage-specific coexpression, we demonstrate monocot- and dicot specific coexpression of cell wall genes. With the expanded coexpression data for multilevel evaluation, ATTED-II provides new opportunities to investigate lineage specific evolution in plants. PMID- 26546320 TI - Laser Microdissection of Grapevine Leaves Reveals Site-Specific Regulation of Transcriptional Response to Plasmopara viticola. AB - Grapevine is one of the most important fruit crops in the world, and it is highly susceptible to downy mildew caused by the biotrophic oomycete Plasmopara viticola. Gene expression profiling has been used extensively to investigate the regulation processes of grapevine-P. viticola interaction, but all studies to date have involved the use of whole leaves. However, only a small fraction of host cells is in contact with the pathogen, so highly localized transcriptional changes of infected cells may be masked by the large portion of non-infected cells when analyzing the whole leaf. In order to understand the transcriptional regulation of the plant reaction at the sites of pathogen infection, we optimized a laser microdissection protocol and analyzed the transcriptional changes in stomata cells and surrounding areas of grapevine leaves at early stages of P. viticola infection. The results indicate that the expression levels of seven P. viticola-responsive genes were greater in microdissected cells than in whole leaves, highlighting the site-specific transcriptional regulation of the host response. The gene modulation was restricted to the stomata cells and to the surrounding areas of infected tissues, indicating that the host response is mainly located at the infection sites and that short-distance signals are implicated. In addition, due to the high sensitivity of the laser microdissection technique, significant modulations of three genes that were completely masked in the whole tissue analysis were detected. The protocol validated in this study could greatly increase the sensitivity of further transcriptomic studies of the grapevine-P. viticola interaction. PMID- 26546322 TI - Cardiac Remodeling, Circulating Biomarkers and Clinical Events in Patients with a History of Atrial Fibrillation. Data from the GISSI-AF Trial. AB - PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia and has an increasing impact on public health because of its morbidity and mortality. Clinical and diagnostic tests to predict the recurrence of arrhythmia and clinical events before AF becomes permanent are still an open issue. METHODS: 307 out of 1442 patients in sinus rhythm, at high risk of recurrence of AF enrolled in the GISSI-AF study, participated in a substudy with echocardiographic and biohumoral evaluation at baseline and at 12-month follow-up. The relations between biomarker concentrations and echocardiographic parameters with study endpoints in 1 year, were analysed by a stepwise multivariable Cox model (entry criteria p < 0.5 and stay criteria p < 0.2). RESULTS: The echocardiographic variables, cardiac markers and clinical variables considered in the statistical model indicated a higher concentration of NT-proBNP at baseline as the strongest factor related to time of first AF recurrence (HR 1.42; 95 %CI 1.23-1.46), first CV hospitalization (HR 1.58; 95 %CI 1.31-1.92) and increasing duration of recurrent AF (OR 2.16; 95 %CI 1.52-3.08). Valsartan treatment was not related to clinical events. CONCLUSIONS: In patients in sinus rhythm with a history of AF a higher concentration of NT-proBNP at baseline was the strongest independent risk factor for first AF recurrence and its duration, and for the first hospital admission for cardiovascular reasons. PMID- 26546321 TI - Extravascular lung water in critical care: recent advances and clinical applications. AB - Extravascular lung water (EVLW) is the amount of fluid that is accumulated in the interstitial and alveolar spaces. In lung oedema, EVLW increases either because of increased lung permeability or because of increased hydrostatic pressure in the pulmonary capillaries, or both. Increased EVLW is always potentially life threatening, mainly because it impairs gas exchange and reduces lung compliance. The only technique that provides an easy measurement of EVLW at the bedside is transpulmonary thermodilution. The validation of EVLW measurements by thermodilution was based on studies showing reasonable correlations with gravimetry or thermo-dye dilution in experimental and clinical studies. EVLW should be indexed to predicted body weight. This indexation reduces the proportion of ARDS patients for whom EVLW is in the normal range. Compared to non indexed EVLW, indexed EVLW (EVLWI) is better correlated with the lung injury score and the oxygenation and it is a better predictor of mortality of patients with acute lung injury or acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution also provides the pulmonary vascular permeability index (PVPI), which is an indirect reflection of the integrity of the alveolocapillary barrier. As clinical applications, EVLWI and PVPI may be useful to guide fluid management of patients at risk of fluid overload, as during septic shock and ARDS. High EVLWI and PVPI values predict mortality in several categories of critically ill patients, especially during ARDS. Thus, fluid administration should be limited when EVLWI is already high. Whatever the value of EVLWI, PVPI may indicate that fluid administration is particularly at risk of aggravating lung oedema. In the acute phase of haemodynamic resuscitation during septic shock and ARDS, high EVLWI and PVPI values may warn of the risk of fluid overload and prevent excessive volume expansion. At the post-resuscitation phase, they may prompt initiation of fluid removal thereby achieving a negative fluid balance. PMID- 26546323 TI - Supplemental oxygen in patients without hypoxia in ST segment elevation myocardial infarction increases myocardial injury and infarct size. PMID- 26546324 TI - Tamsulosin and nifedipine did not improve stone passage over placebo nor were they cost-effective in ureteric stone disease. PMID- 26546325 TI - Graphene oxide liquid crystals: synthesis, phase transition, rheological property, and applications in optoelectronics and display. AB - Graphene oxide (GO) liquid crystals (LCs) are macroscopically ordered GO flakes dispersed in water or polar organic solvents. Since the first report in 2011, GO LCs have attracted considerable attention for their basic properties and potential device applications. In this review, we summarize recent developments and present a comprehensive understanding of GO LCs via many aspects ranging from the exfoliation of GO flakes from graphite, to phases and phase transitions under various conditions, the orientational responses of GO under external magnetic and electric fields, and finally Kerr effect and display applications. The emphasis is placed on the unique and basic properties of GO and their ordered assembly. We will also discuss challenges and issues that need to be overcome in order to gain a more fundamental understanding and exploit full device potentials of GO LCs. PMID- 26546326 TI - Plasmon-Enhanced Light Absorption in GaAs Nanowire Array Solar Cells. AB - In this paper, we propose a plasmon-enhanced solar cell structure based on a GaAs nanowire array decorated with metal nanoparticles. The results show that by engineering the metallic nanoparticles, localized surface plasmon could be excited, which can concentrate the incident light and propagate the energy to nanowires. The surface plasmon can dramatically enhance the absorbance of near bandgap light, and the enhancement is influenced by the size and material of nanoparticles. By optimizing the particle parameters, a large absorbance enhancement of 50 % at 760 nm and a high conversion efficiency of 14.5 % can be obtained at a low diameter and period ratio (D/P ratio) of 0.3. The structure is promising for low-cost high-performance nanoscale solar cells. PMID- 26546327 TI - Aminations with Hypervalent Iodine. AB - Recent progress in the area of hypervalent iodine-mediated and catalyzed amination reaction of hydrocarbons is reviewed. These reactions comprise processes under both intra and intermolecular control and include the functionalization of aromatic C-H bonds as well as conversion of sp-, sp(2)-, and sp(3)-hybridized carbon atoms. These developments demonstrate that hypervalent iodine(III) methodology has reached a high level in amination chemistry. The individual reactions are discussed with a focus on mechanistic details and emphasis is made to the underlying hypervalent iodine reagents, for which structural information is available. PMID- 26546328 TI - Persistence of non-typeable Haemophilus Influenzae in the pharynx of children with adenotonsillar hypertrophy after treatment with azithromycin. AB - This study was performed in children with adenotonsillar hypertrophy to evaluate the effect of azithromycin (AZT) on the presence of NTHi in monocyte/macrophages (CD14(+) cells) of adenoids/tonsils and the persistence of NTHi after adenotonsillectomy. A total of 36 pediatric patients participated in the study: 20 children were treated with AZT before adenotonsillectomy, and 16 children did not receive the antibiotic prior to surgery. NTHi were identified by culture and PCR in swabs and tissue samples. NTHi was detected in the lysates of CD14(+) cells by fluorescence in situ hybridization (FISH) and by culture. The molecular typing was used to cluster NTHi isolates from each child. The intracellular NTHi was found in 10 (62.5%) untreated patients and was identified in three (15%) azithromycin-treated patients (P = 0.003). The proportion of the persistent NTHi strains was similar in both groups. AZT treatment followed by adenotonsillectomy did not completely eliminate NTHi from pharynges; however, it significantly reduced the risk of carriage of Haemophilus influenzae inside the CD14(+) cells. PMID- 26546329 TI - "Clinicopathological features and treatment outcomes of differentiated thyroid cancer in Saudi children and adults". AB - INTRODUCTION: Age is an important prognostic factor in differentiated thyroid cancer (DTC). Our aim was to evaluate differences in clinicopathological features and treatment outcomes among children and adult patients with DTC. MATERIALS AND METHODS: We studied 27 children (below 18 years) with DTC treated during the period 2000-2012 and were compared with (a) 78 adults aged 19-25 years and (b) 52 adults aged 26-30 years treated during the same period in terms of their clinicopathological features and long term treatment outcomes. Locoregional recurrence (LRR), locoregional control (LRC), distant metastasis (DM), distant metastasis control (DMC), disease free survival (DFS) and overall survival (OS) rates were evaluated. RESULTS: Mean age of children was 13.5 years (range: 5-18), while mean age of adults was 24.6 years (range: 19-30). In children, female: male ratio was 2.85:1, and in adults female: male ratio was 7.1:1 (P = 0.041). No significant difference in tumor size was seen between the two groups (P = 0.653). According to American Thyroid Association (ATA) risk stratification classification, the children (85.2 %) were found to have at high risk as compared to adults P = 0.001. Post-thyroidectomy complications and RAI induced toxicities were observed more in children than adults (P = 0.043 and P = 0.041 respectively). LRR occurred in 6 (22.2 %), 9 (11.5 %) and 3 (5.8 %) in age groups of <18 years, 19-25 years and 26-30 years respectively (P = 0.032); while DM was seen in 10 (37.0 %), 9 (10.3 %) and 5 (9.6 %) in age groups of <18 years, 19-25 years and 26-30 years respectively (P = 0.002). Ten year DFS rates were 67.3 % in age group below 18 years, 82.4 % in age group of 19-25 years and 90.1 % in age group of 26-30 years (P = 0.021). CONCLUSION: At the time of diagnosis, children with DTC were found to have more aggressive clinicopathological characteristics. Comparatively lower LRC, DMC and DFS rates in children warrants further multi institutional studies. PMID- 26546330 TI - Survey provides more evidence that patients don't want Sunday GP appointments. PMID- 26546331 TI - Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival. AB - BACKGROUND: The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. METHODS: We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox's proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. RESULTS: A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. CONCLUSIONS: We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules. PMID- 26546333 TI - Capacity building in national influenza laboratories--use of laboratory assessments to drive progress. AB - BACKGROUND: Laboratory testing is a fundamental component of influenza surveillance for detecting novel strains with pandemic potential and informing biannual vaccine strain selection. The United States (U.S.) Centers for Disease Control and Prevention (CDC), under the auspices of its WHO Collaborating Center for Influenza, is one of the major public health agencies which provides support globally to build national capacity for influenza surveillance. Our main objective was to determine if laboratory assessments supported capacity building efforts for improved global influenza surveillance. METHODS: In 2010, 35 national influenza laboratories were assessed in 34 countries, using a standardized tool. Post-assessment, each laboratory received a report with a list of recommendations for improvement. Uptake of recommendations were reviewed 3.2 mean years after the initial assessments and categorized as complete, in-progress, no action or no update. This was a retrospective study; follow-up took place through routine project management rather than at a set time-point post-assessment. WHO data on National Influenza Centre (NIC) designation, External Quality Assessment Project (EQAP) participation and FluNet reporting was used to measure laboratory capacity longitudinally and independently of the assessments. All data was further stratified by World Bank country income category. RESULTS: At follow-up, 81% of 614 recommendations were either complete (350) or in-progress (145) for 32 laboratories (91% response rate). The number of countries reporting to FluNet and the number of specimens they reported annually increased between 2005, when they were first funded by CDC, and 2010, the assessment year (p < 0.01). Improvements were also seen in EQAP participation and NIC designation over time and more so for low and lower-middle income countries. CONCLUSIONS: Assessments using a standardized tool have been beneficial to improving laboratory-based influenza surveillance. Specific recommendations helped countries identify and prioritize areas for improvement. Data from assessments helped CDC focus its technical assistance by country and region. Low and lower-middle income countries made greater improvements in their laboratories compared with upper-middle income countries. Future research could include an analysis of annual funding and technical assistance by country. Our approach serves as an example for capacity building for other diseases. PMID- 26546334 TI - Comparison of FDG PET/CT and MRI in lymph node staging of endometrial cancer. AB - OBJECTIVE: Endometrial cancer is the most frequent cancer occurring in the female genital tract in the Western countries. Because surgical staging is currently the standard, noninvasive techniques that accurately identify lymph node (LN) metastases would be beneficial by reducing costs and complications. The purpose of our study is to compare the diagnostic accuracy of 2-[(18)F]fluoro-2-deoxy-D glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) with that of magnetic resonance imaging (MRI) for detecting LN metastases in the preoperative staging of endometrial cancer. METHODS: Two hundred eighty-seven consecutive patients with endometrial cancer underwent preoperative PET/CT and MRI for staging. The malignancy criteria for LNs were a short diameter of 1 cm or more by MRI and focally increased (18)F-FDG uptake by PET/CT. After evaluating PET/CT and MRI separately, morphologic and functional image findings were compared with the histological findings regarding LN metastasis for all patients. PET/CT and MRI images were classified on the basis of histological findings as true-positive, true-negative, false-positive, or false-negative. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. RESULTS: Histologic examination revealed LN metastases in 51 patients (17.8%). The maximal standardized uptake values (SUVmax) of the primary lesions by PET/CT ranged from 1.4 to 37.7, with a mean value of 9.3, whereas those of the metastatic LNs ranged from 2.0 to 22.5 with a mean of 7.3. On a per-patient basis, node staging resulted in sensitivities of 70.0% with (18)F-FDG PET/CT and 34.0% with MRI, and specificities of 95.4 % with PET/CT and 95.0% with MRI. The NPV of PET/CT was 94.3%, and that of MRI was 87.2%. On a lesion base analysis, sensitivity of PET/CT was 79.4% while that of MRI was 51.6%. In detecting distant metastasis, the sensitivity, specificity, accuracy, PPV, and NPV of PET/CT were 92.9, 98.9, 98.6, 81.3, and 99.6%, respectively. CONCLUSION: Diagnostic performance of FDG PET/CT was better than MRI for detecting metastatic lymph nodes in patients with endometrial cancer both by patient basis and lesion basis analyses. Due to high NPV, FDG PET-CT could aid in selecting candidates for lymphadenectomy. PMID- 26546332 TI - Exposure to sub-chronic and long-term particulate air pollution and heart rate variability in an elderly cohort: the Normative Aging Study. AB - BACKGROUND: Short-term particulate air pollution exposure is associated with reduced heart rate variability (HRV), a risk factor for cardiovascular morbidity and mortality, in many studies. Associations with sub-chronic or long-term exposures, however, have been sparsely investigated. We evaluated the effect of fine particulate matter (PM2.5) and black carbon (BC) exposures on HRV in an elderly cohort: the Normative Aging Study. METHODS: We measured power in high frequency (HF) and low frequency (LF), standard deviation of normal-to-normal intervals (SDNN), and the LF:HF ratio among participants from the Greater Boston area. Residential BC exposures for 540 men (1161 study visits, 2000-2011) were estimated using a spatio-temporal land use regression model, and residential PM2.5 exposures for 475 men (992 visits, 2003-2011) were modeled using a hybrid satellite based and land-use model. We evaluated associations between moving averages of sub-chronic (3-84 day) and long-term (1 year) pollutant exposure estimates and HRV parameters using linear mixed models. RESULTS: One-standard deviation increases in sub-chronic, but not long-term, BC were associated with reduced HF, LF, and SDNN and an increased LF:HF ratio (e.g., 28 day BC: -2.3% HF [95% CI:-4.6, -0.02]). Sub-chronic and long-term PM2.5 showed evidence of relations to an increased LF and LF:HF ratio (e.g., 1 year PM: 21.0% LF:HF [8.6, 34.8]), but not to HF or SDNN, though the effect estimates were very imprecise and mostly spanned the null. CONCLUSIONS: We observed some evidence of a relation between longer-term BC and PM2.5 exposures and changes in HRV in an elderly cohort. While previous studies focused on short-term air pollution exposures, our results suggest that longer-term exposures may influence cardiac autonomic function. PMID- 26546335 TI - Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features. AB - PURPOSE: To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged >= 65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug reaction associations. METHODS: A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged >= 65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. RESULTS: ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged >= 65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1-3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes (p = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. CONCLUSIONS: One out of every 30 urgent admissions of patients aged >= 65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs. PMID- 26546336 TI - Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: a matched case-control study. AB - PURPOSE: Antidepressants, specifically selective serotonin reuptake-inhibiting antidepressants (SSRIs), decrease platelet activation and aggregation in in vitro experiments and could therefore decrease the risk of myocardial infarction (MI). However, prior studies addressing this hypothesis showed contradictory results. Our purpose was to investigate the association between the use of any antidepressant drug and incident MI among middle-aged and older adults. METHODS: We embedded a case-control study in the prospective Rotterdam Study (1991-2011). Controls were matched to MI cases based on sex and age at the same calendar date, and confounding factors were taken into account as time-varying covariates. The relative risk of MI during current and past use of an antidepressant was analyzed with conditional logistic regression with never use of antidepressant drugs as the reference category. RESULTS: A total of 744 out of a cohort of 9499 study participants developed MI during follow-up. After statistical adjustment for traditional cardiovascular risk factors and depression, current use of any antidepressant was associated with a lower risk of MI (odds ratio (OR), 0.71; 95 % confidence interval (CI), 0.51-0.98) compared with never use of any antidepressant. SSRI use showed the lowest relative risk (OR, 0.65; 95 % CI, 0.41 1.02), albeit marginally not statistically significant. Past use of any of the antidepressant classes was not associated with a lower risk of MI. CONCLUSIONS: Current use of antidepressants was associated with a lower risk of MI. Of the different classes, the use of SSRIs showed the lowest risk of MI, and therefore confirming the research hypothesis. PMID- 26546338 TI - "I make efforts, people make comments": Prof. H. Zanyin Gaw-pioneering the world, the trailblazer and founder of China's virology research. PMID- 26546337 TI - Engaging the Community in the Dissemination, Implementation, and Improvement of Health-Related Research. AB - To help maximize the real-world applicability of available interventions in clinical and community healthcare practice, there has been greater emphasis over the past two decades on engaging local communities in health-related research. While there have been numerous successful community-academic partnered collaborations, there continues to be a need to articulate the common barriers experienced during the evolution of these partnerships, and to provide a roadmap for best practices that engage healthcare providers, patients, families, caregivers, community leaders, healthcare systems, public agencies and academic medical centers. To this end, this paper presents a summary of a forum discussion from the 2014 Southern California Dissemination, Implementation and Improvement (DII) Science Symposium, sponsored by the University of California Los Angeles (UCLA) Clinical Translational Science Institute (CTSI), University of Southern California (USC) CTSI, and Kaiser Permanente. During this forum, a diverse group of individuals representing multiple constituencies identified four key barriers to success in community-partnered participatory research (CPPR) and discussed consensus recommendations to enhance the development, implementation, and dissemination of community health-related research. In addition, this group identified several ways in which the over 60 NIH funded Clinical and Translational Science Institutes across the country could engage communities and researchers to advance DII science. PMID- 26546339 TI - Three- and four-dimensional analysis of altered behavior of enteric neural crest derived cells in the Hirschsprung's disease mouse model. AB - BACKGROUND/AIM: The behavior of enteric neural crest-derived cells (ENCC) during enteric nervous system (ENS) development is being gradually understood with the introduction of live-cell imaging. However, many of the analyses to date are two dimensional and the precise multidirectional migration of ENCC has been challenging to interpret. Mice lacking the endothelin-B receptor gene, Ednrb (-/ ) mice, are widely used as a model for Hirschsprung's disease (HD). We have recently developed a Sox10 transgenic (Tg) mouse to visualize ENCC with enhanced green fluorescent protein (Venus). By breeding these two models, we have created a Venus-positive, Sox10 Tg mouse with a deletion of the Ednrb gene, Sox10 Venus(+)/Ednrb (-/-) mouse, to investigate the ENS in HD. The aim of this study was to investigate the behavior of migrating ENCC in the hindgut of the Sox10 Venus(+)/Ednrb (-/-) mouse using three-dimensional and four-dimensional image analysis software. METHODS: To compare the ENCC behavior when the wavefront of ENCC reaches the mid-hindgut between HD mouse and control, we harvested the fetal hindguts of Sox10-Venus(+)/Ednrb (-/-) mice on embryonic day 15.5 (E15.5) and Sox10-Venus(+)/Ednrb (+/+) mice on E12.5, which was used as control. Dissected hindguts were cultured for 360 min and the time-lapse images were obtained using a confocal laser-scanning microscope. Each ENCC at the wavefront was tracked after adjusting the longitudinal axis of the gut to the Y axis and analyzed using Imaris software. RESULTS: Track displacement (TD)-Y indicates ENCC advancement in a rostral-caudal direction. TD-X and TD-Z indicate ENCC advancement perpendicular to the rostral-caudal axis. Mean TD-Y was 34.56 um in HD, but 63.48 um in controls. TD-Y/TD-XZ was not significantly different in both groups. However, the mean track speeds were significantly decreased in HD (72.87 um/h) compared to controls (248.29 um/h). CONCLUSIONS: Our results showed that the track speed of ENCC advancement was markedly decreased in the HD mice compared to controls. This technique provides added information by tracking ENCC with depth perception, which has potential for further elucidating the altered behavior of ENCC in HD. PMID- 26546340 TI - Abdominal radiography is not necessary in children with intussusception. AB - BACKGROUND: Children with intussusception require rapid and accurate diagnosis to enable timely intervention for satisfactory outcome. Ultrasonography is the recommended standard diagnostic modality; however, abdominal radiography (AR) is still used as an initial investigation. The aim of this study was to investigate the benefit of AR in intussusception by determining diagnostic accuracy and analysing correlation of AR findings with outcome. METHODS: Index cases of intussusception presenting over 15 years (1998-2013) were analysed. Those who had AR performed were allocated into groups with positive or normal findings. Outcome of pneumatic reduction of intussusception (PRI) between these groups was compared. RESULTS: Six hundred and forty-four cases of intussusception treated with PRI were identified, 412 (64 %) had AR performed and 232 (36 %) did not. 303 (74 %) radiographs had positive findings and 109 (26 %) were normal. The success rate of PRI did not differ between AR positive (82 %) and AR normal (84 %). Occult pneumoperitoneum was not detected in any patient by AR in our cohort. CONCLUSION: AR is not recommended for the diagnosis of intussusception in children, for the prediction of the outcome of PRI or for the detection of occult pneumoperitoneum. AR should always be performed when clinical peritonism is present but is not otherwise necessary in children with suspected or confirmed intussusception. PMID- 26546341 TI - Reassessment of an Arabidopsis cell wall invertase inhibitor AtCIF1 reveals its role in seed germination and early seedling growth. AB - In higher plants, cell wall invertase (CWI) and vacuolar invertase (VI) are recognized as essential players in sugar metabolism and sugar signaling, thereby affecting source-sink interactions, plant development and responses to environmental cues. CWI and VI expression levels are transcriptionally controlled; however, both enzymes are also subject to posttranslational control by invertase inhibitor proteins. The physiological significances of inhibitor proteins during seed germination and early seedling development are not yet fully understood. Here, we demonstrate that the inhibitor isoform AtCIF1 impacted on seed germination and early seedling growth in Arabidopsis. The primary target of AtCIF1 was shown to be localized to the apoplast after expressing an AtCIF1 YFP fusion construct in tobacco epidermis and transgenic Arabidopsis root. The analysis of expression patterns showed that AtCWI1 was co-expressed spatiotemporally with AtCIF1 within the early germinating seeds. Seed germination was observed to be accelerated independently of exogenous abscisic acid (ABA) in the AtCIF1 loss-of-function mutant cif1-1. This effect coincided with a drastic increase of CWI activity in cif1-1 mutant seeds by 24 h after the onset of germination, both in vitro and in planta. Accordingly, quantification of sugar content showed that hexose levels were significantly boosted in germinating seeds of the cif1-1 mutant. Further investigation of AtCIF1 overexpressors in Arabidopsis revealed a markedly suppressed CWI activity as well as delayed seed germination. Thus, we conclude that the posttranslational modulation of CWI activity by AtCIF1 helps to orchestrate seed germination and early seedling growth via fine-tuning sucrose hydrolysis and, possibly, sugar signaling. PMID- 26546342 TI - Expression of microRNAs and isomiRs in the porcine endometrium: implications for gene regulation at the maternal-conceptus interface. AB - BACKGROUND: Embryo implantation is a complex, synchronized process that requires establishment of a reciprocal dialogue between a receptive endometrium and developing blastocysts. Recently, microRNAs (miRNAs), known to modulate gene expression through post-transcriptional mechanisms, were implicated in regulation of early pregnancy events including maternal recognition of pregnancy and implantation. To characterize complex transcriptomic changes, expression of miRNAs in pregnant and cyclic endometria collected on days 12, 16 and 20 was analyzed using Illumina deep sequencing and analyzed with bioinformatic pipeline. Moreover, expression profiles of ten genes related to miRNA synthesis and transport such as DROSHA, DGCR8, XPO5, DICER, TARBP2, TNRC6A, and AGO1-4 were determined. RESULTS: Among genes involved in miRNA transport and synthesis DROSHA, XPO5, DICER1, TARBP, and AGO1 expression was affected by the reproductive status. Moreover, DICER1 and AGO2 proteins were localized in luminal and glandular epithelium with immunofluorescence staining. Several hundred mature, canonical and non-canonical miRNAs were found to be expressed in the endometrial samples. Detailed analysis revealed that miRNA length variants, isomiRs, accounted for the vast majority of defined sequences. Both miRNA and isomiR of miR-140-3p were shown to affect expression of putative targets in endometrial stromal cells in vitro. Computational analysis of putative target genes for miRNAs differentially expressed (DE) between pregnant and cyclic animals resulted in lists of biological processes and regulatory pathways indicating their role in cellular development, cell cycle, immunological response and organismal development. Among predicted target genes for DE miRNAs, vascular endothelial growth factor (VEGF), progesterone and estradiol receptors (PGR, ESR1) and leukemia inhibitory factor (LIF) were found. CONCLUSIONS: This research revealed a repertoire of pregnancy-related miRNAs in porcine endometrium during initial stages of conceptus implantation and during the estrous cycle, and sheds light on mechanisms regulating miRNA-mediated gene expression at the maternal-conceptus interface. PMID- 26546344 TI - Correction. PMID- 26546343 TI - Summer heat: a cross-sectional analysis of seasonal differences in sexual behaviour and sexually transmissible diseases in Melbourne, Australia. AB - OBJECTIVES: To date, no study has correlated seasonal differences in sexual behaviour with the seasonal differences in sexually transmitted infections (STIs); and no seasonal study of STIs has been conducted in the southern hemisphere. Our study aimed to describe seasonal differences in sexual behaviour and correlate this with seasonal differences in STI diagnoses in Melbourne, Australia. METHOD: This was a cross-sectional study of individuals attending the Melbourne Sexual Health Centre over a 9-year period from 2006 to 2014. We conducted separate analyses for men who have sex with men (MSM) and men who have sex with women (MSW), and women. Seasonal patterns of sexual behaviour and STI positivity were examined within each group. RESULTS: All groups reported a higher number of partners over the preceding three months for consultations in summer compared with winter (MSM mean 5.48 vs 5.03; MSW mean 2.46 vs 2.31; women mean 1.83 vs 1.72). Urethral gonorrhoea diagnoses among MSM were higher in summer compared with winter (OR 1.23, 95% CI 1.04 to 1.46). Similarly, non-gonococcal urethritis (NGU) diagnoses among MSW were the highest in summer (OR 1.11, 95% CI 1.03 to 1.20), but there was no seasonal difference in NGU diagnoses when we adjusted for partner numbers. In women, pelvic inflammatory disease (PID) diagnoses peaked in autumn, when rates were higher than in winter (OR 1.30, 95% CI 1.09 to 1.55). CONCLUSIONS: Our results describe a peak in sexual partner number and STI diagnoses during consultations in summer in men and a rise in PID in autumn in women. PMID- 26546345 TI - Epicardial Catheter Ablation Using High-Intensity Ultrasound: Validation in a Swine Model. AB - BACKGROUND: Epicardial radiofrequency catheter ablation of ventricular tachycardia remains challenging because of the presence of deep myocardial scar and adjacent cardiac structures, such as the coronary arteries, phrenic nerve, and epicardial fat that limit delivery of radiofrequency energy. High-intensity ultrasound (HIU) is an acoustic energy source able to deliver deep lesions through fat, while sparing superficial structures. We developed and tested an epicardial HIU ablation catheter in a closed chest, in vivo swine model. METHODS AND RESULTS: The HIU catheter is an internally cooled, 14-French, side-facing catheter, integrated with A-mode ultrasound guidance. Swine underwent percutaneous subxyphoid epicardial access and ablation with HIU (n=10 swine) at 15, 20, and 30 W. Compared with irrigated radiofrequency lesions in control swine (n = 5), HIU demonstrated increased lesion depth (HIU 11.6+/-3.2 mm versus radiofrequency 4.7+/-1.6 mm; mean+/-SD) and epicardial sparing (HIU 2.9+/-2.1 mm versus radiofrequency 0.1+/-0.2 mm) at all HIU powers, and increased lesion volume at HIU 20 and 30 W (P<0.0001 for all comparisons). HIU ablation over coronary arteries and surrounding epicardial fat resulted in deep lesions with normal angiographic flow. Histological disruption of coronary adventitia, but not media or intima, was noted in 44% of lesions. CONCLUSIONS: Compared with radiofrequency, HIU ablation in vivo demonstrates significantly deeper and larger lesions with greater epicardial sparing in a dose-dependent manner. Further development of this catheter may lead to a promising alternative to epicardial radiofrequency ablation. PMID- 26546346 TI - Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy. AB - BACKGROUND: Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. METHODS AND RESULTS: We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO-EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56+/-44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on beta-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. CONCLUSIONS: The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs. PMID- 26546348 TI - Improvement of spontaneous locomotor activity with JAK inhibition by JTE-052 in rat adjuvant-induced arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction, disability, and decreased quality of life (QOL). Inhibition of Janus kinase (JAK) signaling ameliorates articular inflammation and joint destruction in animal models of RA, but its effects on behaviors indicating well-being are poorly understood. In this study, we evaluated the effect of JAK inhibition on spontaneous locomotor activity in rats with adjuvant-induced arthritis, a rodent model of RA. METHODS: Arthritis was induced in male Lewis rats by a single subcutaneous injection of Freund's complete adjuvant. The novel JAK inhibitor JTE-052 was orally administered for 7 days after the onset of arthritis. RESULTS: Induction of arthritis suppressed the spontaneous locomotor activity of the rats. Administration of JTE-052 completely improved the spontaneous locomotor activity, with partial reductions in articular inflammation and joint destruction. Hyperalgesia and motor functions were also improved, but the efficacy was not complete. However, serum interleukin (IL)-6 levels were completely decreased at 4 h after administration of the first dose of JTE-052. CONCLUSIONS: This study demonstrated that JAK inhibition improved the spontaneous locomotor activity of rats with adjuvant-induced arthritis, in association with amelioration of pain and physical dysfunction as a consequence of suppression of joint inflammation. Moreover, although further studies are needed, there was possible participation of IL-6 downregulation in the improvement of locomotor activity by JAK inhibition. PMID- 26546349 TI - Echocardiographic and biochemical analysis of cardiac function and injury among female amateur runners post-marathon. AB - BACKGROUND: Numerous studies with male amateur runners have determined negative changes in their cardiac function/of their myocard following long endurance loads. This study aims to examine such potential changes in women, specifically, after running a marathon. METHODS: A total of 18 female amateur runners (39.5 +/- 10.5 years) were examined before (T1), immediately after (T2) and 24 h post marathon (T3). An echocardiography was performed using Tissue Doppler (TD) imaging. In addition, the concentration of cardiac troponin T (cTnT) and the activity of the myocardial muscle creatine kinase (CK-MB) were determined at T1 and T2. RESULTS: The echocardiographic parameters revealed impairment of the diastolic function, without, however, documenting a diastolic dysfunction (in accordance with the classification of Nagueh (J Am Soc Echocardiogr, 22:107-33, 2009)). The ratio of blood flow velocity through the mitral valve during early versus late diastole (MV E/A ratio), for example, decreased. The values measured at T3 were similar to those measured at T1. The ratio of early transmitral diastolic filling velocity and of the transmitral diastolic filling velocity by TD imaging (MV E/E') did not indicate any change from T1 to T2, but a significant increase at T3 (in comparison with T1). The systolic function (measured by the left ventricular ejection fraction) did not change significantly. The cTnT concentration and CK-MB activity were significantly higher in T2 than in T1. CONCLUSION: The data collected does not provide any solid evidence of pathological changes in the cardiac function of female amateur runners post marathon, although the lab values indicate a strongly increased myocardial stimulation. PMID- 26546350 TI - Factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children. AB - BACKGROUND: The increasing prevalence of overweight and obesity among children is often associated with motor deficits. Motor performance among children partly depends on modifiable factors, for example, weight status, electronic media use, sports club participation, and on nonmodifiable factors, for example, sex, age, migration background, or socio-economic status. AIM: To evaluate factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children. METHODS: Height, weight, and sport motor performance of primary school children were measured using the German motor performance test DMT 6-18. In addition, children were asked about migration background, sports club participation, and electronic media use in their room. RESULTS: A total of 304 children (48.7% girls) with a mean age of 8.0 +/- 1.2 years were tested. In total, 61 (20.1%) children were overweight or obese. Regarding motor performance, nonoverweight children showed significantly higher total z-scores (106.8 +/- 5.7 vs. 102.4 +/- 6.8). For the total cohort, results of the multiple linear regression analysis (R (2) = 0.20) revealed that factors male sex (beta = 0.12), nonoverweight children (beta = 0.28), higher school grade (beta = 0.23), sports club participation (beta = 0.18),and > 2 weekly lessons of physical education (beta = 0.26) were associated with an increased motor performance. For nonoverweight children results of the multiple linear regression analysis (R (2) = 0.09) found that a higher school grade (beta = 0.17), sports club participation (beta = 0.16),and more than 2 weekly lessons of physical education (beta = 0.22) were associated with an increased motor performance. For the overweight children, results of the multiple linear regression analysis (R (2) = 0 .43) showed that no migration background (beta = 0.23), a higher school grade (beta = 0.55), sports club participation (beta = 0.33) and more than 2 weekly lessons of physical education (beta = 0.48) were associated with an increased motor performance. CONCLUSION: Regarding modifiable factors, motor performance among overweight and nonoverweight children is strongly associated with a higher number of weekly lessons in physical education. Therefore, daily lessons in physical education are strongly recommended to improve motor performance especially among overweight primary school children. PMID- 26546347 TI - Time course of cardiometabolic alterations in a high fat high sucrose diet mice model and improvement after GLP-1 analog treatment using multimodal cardiovascular magnetic resonance. AB - BACKGROUND: Cardiovascular complications of obesity and diabetes are major health problems. Assessing their development, their link with ectopic fat deposition and their flexibility with therapeutic intervention is essential. The aim of this study was to longitudinally investigate cardiac alterations and ectopic fat accumulation associated with diet-induced obesity using multimodal cardiovascular magnetic resonance (CMR) in mice. The second objective was to monitor cardiac response to exendin-4 (GLP-1 receptor agonist). METHODS: Male C57BL6R mice subjected to a high fat (35 %) high sucrose (34 %) (HFHSD) or a standard diet (SD) during 4 months were explored every month with multimodal CMR to determine hepatic and myocardial triglyceride content (HTGC, MTGC) using proton MR spectroscopy, cardiac function with cine cardiac MR (CMR) and myocardial perfusion with arterial spin labeling CMR. Furthermore, mice treated with exendin 4 (30 MUg/kg SC BID) after 4 months of diet were explored before and 14 days post treatment with multimodal CMR. RESULTS: HFHSD mice became significantly heavier (+33 %) and displayed glucose homeostasis impairment (1-month) as compared to SD mice, and developed early increase in HTGC (1 month, +59 %) and MTGC (2-month, +63 %). After 3 months, HFHSD mice developed cardiac dysfunction with significantly higher diastolic septum wall thickness (sWtnD) (1.28 +/- 0.03 mm vs. 1.12 +/- 0.03 mm) and lower cardiac index (0.45 +/- 0.06 mL/min/g vs. 0.68 +/ 0.07 mL/min/g, p = 0.02) compared to SD mice. A significantly lower cardiac perfusion was also observed (4 months:7.5 +/- 0.8 mL/g/min vs. 10.0 +/- 0.7 mL/g/min, p = 0.03). Cardiac function at 4 months was negatively correlated to both HTGC and MTGC (p < 0.05). 14-day treatment with Exendin-4 (Ex-4) dramatically reversed all these alterations in comparison with placebo-treated HFHSD. Ex-4 diminished myocardial triglyceride content (-57.8 +/- 4.1 %), improved cardiac index (+38.9 +/- 10.9 %) and restored myocardial perfusion (+52.8 +/- 16.4 %) under isoflurane anesthesia. Interestingly, increased wall thickness and hepatic steatosis reductions were independent of weight loss and glycemia decrease in multivariate analysis (p < 0.05). CONCLUSION: CMR longitudinal follow-up of cardiac consequences of obesity and diabetes showed early accumulation of ectopic fat in mice before the occurrence of microvascular and contractile dysfunction. This study also supports a cardioprotective effect of glucagon-like peptide-1 receptor agonist. PMID- 26546351 TI - Treatment of proximal humerus fractures in children and young adolescents. AB - BACKGROUND: Fractures of the proximal humerus in children are rare and represent approximately 0.45% of all paediatric fractures. These injuries are common in patients up to an age of 16 years. The treatment of displaced subcapital fractures is still controversially discussed in literature. Therefore the aim of this study was to evaluate the short-term outcome and to provide guidelines for surgical treatment of these fractures in children and adolescents. METHODS: Clinical and radiological results of 231 patients between 0 and 17 years with subcapital humerus fractures were evaluated. Patients were devided according to their treatment as followed (1) conservative treatment group (2) operative treatment group. RESULTS: A total of 191 patients (82.7%) underwent conservative treatment and 40 (17.3%) underwent operative treatment. Surgical treatment consisted of open reduction and internal fixation (ORIF) (35.0%) or closed reduction and internal fixation (CRIF) (52.5%). In all operated patients an axial deviation of more than 20 degrees was observed preoperatively. According to our groups; the surgical group presented in 90% (N = 36) of the patients with an excellent result, in 5% (N = 2) an average result was observed and in 5% (N = 2) a poor result according to Constant Murley Score was achieved. In the conservative treatment group in 185 patients (96.9%) excellent results were achieved and in 6 patients (3.1%) an average result in the Constant Murley Score was achieved. CONCLUSION: Conservative treatment in children < 10 years and an angulation angle < 20 degrees , as well as surgical treatment with ORIF or CRIF in patients > 10 years and with an angulation angle > 20 degrees leads to excellent short-term outcome. However, studies with longer observation time are needed to evaluate long-term complications like limb length discrepancy. PMID- 26546352 TI - [Not Available]. PMID- 26546353 TI - Medical studies and Nazi medicine: Nazi medicine as perceived by Austrian medical students. AB - BACKGROUND: Austrian medical universities have not covered the topic of Nazi medicine in their curricula to any satisfactory degree to date. In the context of medical-ethical education and on-going medical ethics debates, it seems indispensable to be confronted also with the dark chapters of medical history, and especially Nazi medicine. Students should learn to understand controversial discussions, e.g. about euthanasia, in a historical context. The purpose of this study was to investigate whether students had, during their studies, been confronted with Nazi medical crime and whether they considered such a confrontation as important. The survey also focused on extant knowledge about this topic. METHODS: From late 2012 to May 2013, 341 late semester students of the medical universities in Vienna, Graz, and Innsbruck were questioned about the coverage of Nazi medicine during their courses, using multiple choice questionnaires. The data were evaluated using a descriptive-statistical approach. RESULTS: The study has shown a low level of knowledge of students about Nazi medicine in the three universities. Only a third of the students had ever heard about "Aktion T4". About 65% of the participants found it important to be comprehensively informed about Nazi medicine during their studies, e.g. with a view to their future career. On average across the three universities, only 43% of the students had been confronted with this topic. CONCLUSION: The study found a clear wish for more information about Nazi medicine. Universities should, therefore, offer students various opportunities and ways of discussing this issue in the university context. PMID- 26546354 TI - Differences among South Tyrolean suicides: a psychological autopsy study. AB - OBJECTIVE: The aim of the present study was to study gender differences in the suicides in South Tyrol. METHODS: Between 2000 and 2009, the Department of Psychiatry of Bolzano administered questionnaires to the Provincial Departments of Public Health requesting information about causes and methods of completed suicides. Each suicide was then examined using a psychological autopsy methodology. RESULTS: There were 448 suicides studied (339 men and 109 women). Compared with men, women were more likely to live alone, have attempted suicide in the past, and to have contacted their general practitioners in the last weeks before dying. They were also less likely to have an alcohol use disorder, have used violent methods of suicide, and be 35 years or younger. CONCLUSION: The differences identified for South Tyrolean suicides confirmed previously reported gender differences in employment and marital status, history of a previous suicide attempt, and alcohol abuse. Appropriate gender-based preventive interventions are needed. PMID- 26546355 TI - Serum soluble urokinase-type plasminogen activator receptor and interferon-gamma induced protein 10 levels correlate with significant fibrosis in chronic hepatitis B. AB - BACKGROUND: Hepatitis B virus (HBV) presents an important public health problem. Liver biopsy is currently the gold standard for assessing the degree of intrahepatic inflammation and for staging liver fibrosis. However, the value of liver biopsies is limited by sampling errors, understaging and interobserver variability in interpretation. There is, therefore, a need to identify novel, non invasive serologic biomarkers for the development of new predictive models of fibrosis. METHODS: We enrolled patients with chronic hepatitis B infection (CHB) and examined the relationships between serum soluble urokinase plasminogen activator receptor (suPAR) and interferon-induced protein-10 (IP-10), and the results of liver biopsies. Healthy volunteers with normal aminotransferase levels and negative serological results for HBV, hepatitis C virus and human immunodeficiency virus were recruited as controls. RESULTS: Mean platelet volume, serum suPAR and IP-10 were significantly elevated in patients with CHB compared with controls. Median serum suPAR and IP-10 levels were significantly higher in patients with liver fibrosis compared with patients with mild fibrosis. There was no significant difference in mean platelet volume or aspartate aminotransferase to-platelet ratio index scores between patients with mild and significant fibrosis. CONCLUSION: suPAR and IP-10 were able to distinguish between significant and mild fibrosis with good sensitivity and specificity, and may thus represent useful biomarkers for identifying patients with significant fibrosis. PMID- 26546356 TI - Challenges of the epidemiological and economic burdens associated with hypertension in middle income countries: evidence from Mexico. AB - BACKGROUND: In order to identify the challenges resulting from hypertension in a middle income country, this study has developed probabilistic models to determine the epidemiological and economic burden of hypertension in Mexico. METHODS: Considering a population base of 654,701 reported cases of adults with hypertension, we conducted a longitudinal analyses in order to identify the challenges of epidemiological changes and health care costs for hypertension in the Mexican health system. The cost-evaluation method used was based on the instrumentation technique. To estimate the epidemiological changes for 2015-2017, probabilistic models were constructed according to the Box-Jenkins technique. RESULTS: Regarding changes in expected cases for 2015 vs. 2017, an increase of 12 % is expected (p < 0.001). Comparing the economic impact in 2015 versus 2017 (p < 0.001), there is a 23 % increase in financial requirements. The total amount for hypertension in 2016 (US dollars) will be $6306,685,320 Of these, $ 2990,109,035 will be as direct costs and $ 3316,576,285 as indirect costs. CONCLUSIONS: If the risk factors and care models remain as they are currently in the health system, the financial consequences will have a major impact on the out-of-pocket users, following in order of importance, on social security providers and on public assistance providers. PMID- 26546357 TI - Predicting the outcome of head-up tilt test using heart rate variability and baroreflex sensitivity parameters in patients with vasovagal syncope. AB - PURPOSE: The aim of the study was to investigate whether a statistical model could be used for an early prediction of the head-up tilt test (HUTT) outcome from heart rate variability (HRV) and baroreflex sensitivity (BRS) data obtained during early stages of the HUTT. METHODS: A modified Italian protocol was used for HUTT in 105 patients with a previous history of vasovagal syncope. Beat-to beat heart rate and blood pressure were continuously recorded. Fast Fourier transformation was used for spectral analysis of HRV and a sequence technique for measuring the BRS. RESULTS: Linear statistical models based on HRV and BRS data from the first 15 min of HUTT were no more accurate than always naively predicted majority class that a syncope will occur (average model out-of-sample accuracy 56.2 +/- 5.1 % vs. majority class relative frequency 54.2 %). Even when HRV and BRS data from the first 30 min were used in the model, we did not obtain any predictions of meaningful practical value (75.0 +/- 5.1 % accuracy vs. 72.2 % majority class). CONCLUSIONS: While there are discernible and meaningful differences between HUTT-P and HUTT-N subjects, they are not sufficient to discriminate between the two groups and predict a syncope early in the HUTT. The results might improve with a larger set of subjects; however, we can conclude that it is not likely that syncope predictions of practical value can be obtained from aggregate HRV spectral analysis and BRS values. PMID- 26546358 TI - Immune thrombocytopenic purpurae presenting with cortical vein thrombosis: is it rebalanced hemostasis? PMID- 26546359 TI - The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia. AB - The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (>=70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements. PMID- 26546360 TI - Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes. AB - The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes. PMID- 26546361 TI - Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis. AB - To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p.R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function of KCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches. PMID- 26546362 TI - Glutaminase-containing microvesicles from HIV-1-infected macrophages and immune activated microglia induce neurotoxicity. AB - BACKGROUND: HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate. RESULTS: MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1 infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs. CONCLUSIONS: These findings support MVs as a potential pathway/mechanism of excessive glutamate generation and neurotoxicity in HAND and therefore MVs may serve as a novel therapeutic target. PMID- 26546363 TI - Prediction of hemodynamic reactivity using dynamic variations of Analgesia/Nociception Index (?ANI). AB - The Analgesia/Nociception Index (ANI), a 0-100 non-invasive index calculated from heart rate variability, reflects the analgesia/nociception balance during general anesthesia. We hypothesized that dynamic variations of ANI (?ANI) would provide better performance than static values to predict hemodynamic reactivity during desflurane/remifentanil general anesthesia. One hundred and twenty-eight patients undergoing ear-nose-throat or lower limb orthopedic surgery were analyzed in this prospective observational study. The ANI, heart rate and systolic blood pressure were recorded before induction, at skin incision, during procedure and at emergence from general anesthesia. Changes in these variables were recorded after 1 min for ANI (ANI1min) and 5 min for heart rate and systolic blood pressure. The dynamic variation of ANI at the different time points was defined as: ?ANI = (ANI1min - ANI)/([ANI + ANI1min]/2). Receiver-operating characteristic (ROC) curves were built to evaluate the performance of ANI, ANI1 min and ?ANI to predict hemodynamic reactivity (increase by more than 20 % in heart rate and/or systolic blood pressure within 5 min). For the prediction of hemodynamic reactivity, better performance was observed with ?ANI (area under ROC curve (AUC ROC) = 0.90) in comparison to ANI (ROC AUC = 0.50) and ANI1min (ROC AUC = 0.77). A ?ANI threshold of -19 % predicts hemodynamic reactivity with 85 % [95 % CI 77 91] sensitivity and 85 % [95 % CI 81-89] specificity. Dynamic variations of ANI provide better performance than static values to predict hemodynamic reactivity during desflurane/remifentanil general anesthesia. These findings may be of interest for the individual adaptation of remifentanil doses guided by ?ANI during general anesthesia, although this remains to be demonstrated. PMID- 26546364 TI - Physiological differences between bud breaking and flowering after dormancy completion revealed by DAM and FT/TFL1 expression in Japanese pear (Pyrus pyrifolia). AB - The regulatory mechanisms underlying bud breaking (scale leaf elongation) and flowering in the lateral flower buds of Japanese pear (Pyrus pyrifolia Nakai 'Kosui') are unknown. To more fully characterize these processes, we treated pear trees with different amounts of chilling initiated at different times. Chilling for ~900 h at 6 degrees C always induced bud breaking (scale elongation in >=70% lateral flower bud) when provided between October and February, whereas chilling provided earlier (between October and December) was less effective on flowering (floret growth and development) than later chilling and the flowering rate increased with longer chilling durations. During chilling, the expression of pear DAMs (PpMADS13-1, 13-2 and 13-3) in lateral flower buds decreased as chilling accumulated irrespective of the timing of chilling. In addition, pear TFL1 (PpTFL1-1a) in the lateral flower buds was expressed at higher levels when the time interval for chilling was earlier. On the other hand, during forcing at 15 degrees C after chilling, the expression pattern of all three PpMADS13 genes was similar among the treatments, and the expression levels seemed lower in the treatment where scale leaves of the lateral flower bud elongated faster, whereas pear FT (PpFT2a) was expressed at higher levels in the buds whose flower clusters elongated more vigorously during forcing. From these results, we infer that flowering time may be mediated via the balance of flowering-related genes FT and TFL1, whereas bud breaking may be regulated via the DAM genes in Japanese pear. PMID- 26546365 TI - Symbiotic association between Salix purpurea L. and Rhizophagus irregularis: modulation of plant responses under copper stress. AB - There are increasing concerns about trace metal levels such as copper (Cu) in industrial sites and the broader environment. Different studies have highlighted the role of mycorrhizal associations in plant tolerance to trace metals, modulating some of the plant metabolic and physiological responses. In this study, we investigated the role of the symbiotic association betweenRhizophagus irregularisandSalix purpureaL. in modulating plant responses under Cu stress. We measured Cu accumulation, oxidative stress-related, photosynthetic-related and hydraulic traits, for non-inoculated (non-arbuscular mycorrhizal fungi) and inoculated saplings exposed to different Cu concentrations. We found thatS. purpureais a suitable option for phytoremediation of Cu, acting as a phytostabilizer of this trace metal in its root system. We observed that the symbiotic association modulates a broad spectrum of metabolic and physiological responses inS. purpureaunder Cu conditions, including (i) a reduction in gas exchange associated with chlorophyll content changes and (ii) the sequestration of Cu into the cell walls, modifying vessels anatomy and impacting leaf specific conductivity (KL) and root hydraulic conductance (LP). UpholdingKLandLPunder Cu stress might be related to a dynamic Aquaporin gene regulation ofPIP1;2along with an up-regulation ofTIP2;2in the roots of inoculatedS. purpurea. PMID- 26546366 TI - Reliance on shallow soil water in a mixed-hardwood forest in central Pennsylvania. AB - We investigated depth of water uptake of trees on shale-derived soils in order to assess the importance of roots over a meter deep as a driver of water use in a central Pennsylvania catchment. This information is not only needed to improve basic understanding of water use in these forests but also to improve descriptions of root function at depth in hydrologic process models. The study took place at the Susquehanna Shale Hills Critical Zone Observatory in central Pennsylvania. We asked two main questions: (i) Do trees in a mixed-hardwood, humid temperate forest in a central Pennsylvania catchment rely on deep roots for water during dry portions of the growing season? (ii) What is the role of tree genus, size, soil depth and hillslope position on the depth of water extraction by trees? Based on multiple lines of evidence, including stable isotope natural abundance, sap flux and soil moisture depletion patterns with depth, the majority of water uptake during the dry part of the growing season occurred, on average, at less than ~60 cm soil depth throughout the catchment. While there were some trends in depth of water uptake related to genus, tree size and soil depth, water uptake was more uniformly shallow than we expected. Our results suggest that these types of forests may rely considerably on water sources that are quite shallow, even in the drier parts of the growing season. PMID- 26546367 TI - Design and Performance of a Low-Cost Telemetric Laparoscopic Tactile Grasper. AB - Tactile feedback is completely lost in laparoscopic surgery, which would provide information about tissue compliance, texture, structural features, and foreign bodies. We developed a system with artificial tactile feedback for laparoscopic surgery that consists of a telemetric tactile laparoscopic grasper, a remote PC with customized software, and a commercial video-mixer. A standard, nonsensorized laparoscopic grasper was customized to allow the integration of a tactile sensor and its electronics. The tactile sensor and the electronics module were designed to be detachable from the instrument. These parts are lightweight and wireless, thus not impeding the use of the device as surgical instrument. The remaining system components used to generate visualization of the tactile data do not influence the workflow in the operating room. The overall system design of the described instrumentation allows for easy implementation in an operating room environment. The fabrication of the tactile sensor is relatively easy and the production costs are low. With this telemetric laparoscopic grasper instrument, systematic preclinical studies can be performed in which surgeons execute surgical tasks that are derived from clinical reality. The experience gained from these investigations could then be used to define the requirements for any further development of artificial tactile feedback systems. PMID- 26546368 TI - Feasibility of Subxiphoid Anatomic Pulmonary Lobectomy in a Canine Model. AB - Purpose Transthoracic thoracoscopic approach is the gold standard in surgical treatment for thoracic disease. However, it is associated with significant chronic postoperative wound discomfort. Currently, limited data are available regarding the subxiphoid approach to the thoracic cavity. The present study is aimed to evaluate the performance of a subxiphoid anatomic pulmonary lobectomy (SAPL) in a canine model. Methods The SAPL procedure was performed in 10 beagle dogs using a 3-cm incision over the xiphoid process. After thoracic exploration, SAPL was performed under flexible bronchoscopy guidance. The pulmonary vessel was divided with Ligasure and secured with a suture ligature. The bronchus was divided with endostapler. Surgical outcomes were evaluated by the success of SAPL and operative complications. Results SAPL was successfully completed in 9 animals. One animal required conventional thoracotomy to resuture the pulmonary artery stump. Another animal encountered small middle lobe laceration after SAPL and died at 8 days postoperation due to respiratory distress. Conclusion Subxiphoid anatomic pulmonary lobectomy is technically feasible. Refinement of endoscopic instruments combined with more research evidences may facilitate the development of subxiphoid platform in thoracic surgery. PMID- 26546369 TI - Knockdown of hippocampal cysteinyl leukotriene receptor 1 prevents depressive behavior and neuroinflammation induced by chronic mild stress in mice. AB - RATIONALE: Numerous studies have demonstrated that neuroinflammation is associated with depression-like symptoms and neuropsychological disturbances, and cysteinyl leukotriene receptor 1 (CysLT1R) was reported to be involved in neuroinflammation. The pathophysiological role of CysLT1R has been reported in several types of brain damage. However, the role of CysLT1R in depression remains to be elucidated. OBJECTIVES: We aimed to investigate the effect of hippocampal CysLT1R downregulation on depressive behaviors and neuroinflammatory responses in mice exposed to chronic mild stress (CMS). RESULTS: We firstly found that expression of hippocampal CysLT1R was gradually increased over CMS exposure, while 3 weeks treatment with fluoxetine reversed the increment of hippocampal CysLT1R expression. Hippocampal CysLT1R knockdown suppressed CMS-induced depressive-like behaviors as evidenced by decreases in immobility time in tail suspension test (TST), decreased latency to feed in novelty-suppressed feeding (NSF) test, and by increase in the number of entries and decrease in time spent in the open arm in elevated plus maze (EPM) test. Increments of hippocampal NF kappaB p65, IL-1beta, and TNF-alpha induced by CMS were also prevented by hippocampal CysLT1R knockdown beforehand. CONCLUSIONS: Hippocampal CysLT1R participates in depression, and knockdown of hippocampal CysLT1R prevents CMS induced depressive-like behaviors and neuroinflammation, suggesting that suppression of CysLT1R could prevent the development of depression. PMID- 26546371 TI - A disseminated Mycoplasma hominis infection in a patient with an underlying defect in humoral immunity. AB - Non-urogenital Mycoplasma hominis infections are rare, but may cause life threatening complications. We describe a case of disseminated M. hominis infection with extensive abscess formation in an immunocompromised patient with iatrogenic hypogammaglobulinemia under rituximab treatment. PMID- 26546370 TI - Role of the basolateral amygdala dopamine receptors in arachidonylcyclopropylamide-induced fear learning deficits. AB - There is much evidence suggesting that the mesoamygdala dopaminergic (DAergic) system plays a crucial role in the formation and expression of fear conditioning, with both D1 and D2 receptors being involved. In addition, cannabinoid CB1 receptor (CB1R) signaling modulates DAergic pathways. The present study sought to determine the involvement of basolateral amygdala (BLA) dopamine receptors in arachidonylcyclopropylamide (ACPA)-induced fear learning deficits. Context- and tone-dependent fear conditioning in adult male NMRI mice was evaluated. Pre training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing in context- or tone-dependent fear conditioning, suggesting an acquisition impairment. Pre-training intra-BLA microinjection of a subthreshold dose of SKF38393 (D1-like receptor agonist), SCH23390 (D1-like receptor antagonist), quinpirole (D2-like receptor agonist), or sulpiride (D2 like receptor antagonist) did not alter the context-dependent fear learning deficit induced by ACPA, while SKF38393 or quinpirole restored ACPA effect on tone-dependent fear learning. Moreover, SKF38393 (1 MUg/mouse), SCH23390 (0.04 and 0.08 MUg/mouse), or quinpirole (0.1 MUg/mouse) all impaired context-dependent fear learning. It is concluded that D1 or D2 dopamine (DA) receptor activation restores tone- but not context-dependent fear learning deficit induced by CB1 activation using ACPA. PMID- 26546372 TI - Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children. AB - OBJECTIVE: The aim of this study was to collect data about pediatric Gram negative bloodstream infections (BSI) to determine the factors that influence multidrug resistance (MDR), clinical course and outcome of children affected by Gram-negative sepsis. METHODS: In this observational, prospective, multicenter study we collected cases of pediatric Gram-negative BSI during a 2-year period. We analyzed epidemiological, microbiological and clinical factors that associated with acquisition of MDR infections and outcome. RESULTS: One-hundred and thirty five BSI episodes were analyzed. Median age of children was 0.5 years (IQR 0.1 6.17, range 0-17 years). Predominant bacteria were Enterobacteriaceae (68.3 %), and Pseudomonas spp. (17.9 %). Multidrug resistance was detected in 45/134 cases (33.6 %), with the highest rates in Escherichia coli, Enterobacter and Pseudomonas spp. Acquisition of MDR pathogens was significantly associated with prior cephalosporin treatment, older age, admission to hemato-oncology unit, polymicrobial infections, higher rate of development of septic shock, and multiple organ failures. All-cause mortality was 17.9 %. Presence of septic shock at presentation and parenteral nutrition were associated with higher mortality. Pseudomonas spp., and Enterobacter spp. BSIs had the highest rate of mortality. Inappropriate empiric antibiotic therapy was more frequent in MDR patients, although not significantly associated with poor outcome. CONCLUSION: Rates of multidrug resistance and mortality in children with Gram-negative bloodstream infections remain high in our settings. Empiric broad-spectrum antibiotics and combination therapy could be recommended, especially in children with malignant diseases, patients admitted to the PICU, and for cases with septic shock, who have higher mortality risk. PMID- 26546373 TI - Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure. AB - PURPOSE: Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. METHODS: This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. RESULTS: It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. CONCLUSION: These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility. PMID- 26546374 TI - Low-Level Vagus Nerve Stimulation Attenuates Myocardial Ischemic Reperfusion Injury by Antioxidative Stress and Antiapoptosis Reactions in Canines. AB - BACKGROUND: Low-level vagus nerve stimulation (LL-VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion (I/R) injury. However, the underlying mechanism of this protective effect remains unknown. OBJECTIVE: This study aimed to test the hypothesis that LL-VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions. METHOD: Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL-VNS group (N = 9, I/R plus LL-VNS), and sham group (N = 9, sham surgery without LL-VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis. RESULTS: LL-VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL-VNS in the I/R group induced the opposite effect compared with the sham group. CONCLUSION: LL-VNS exerts protective effects on myocardial I/R injury. Its potential mechanisms involve the suppression of oxidative stress and cellular apoptosis. PMID- 26546375 TI - Correlated polymorphism in cytotype and sexual system within a monophyletic species, Lycium californicum. AB - BACKGROUND AND AIMS: Polyploidy has important effects on reproductive systems in plants and has been implicated in the evolution of dimorphic sexual systems. In particular, higher ploidy is associated with gender dimorphism across Lycium species (Solanaceae) and across populations within the species Lycium californicum. Previous research on the association of cytotype and sexual system within L. californicum sampled a limited portion of the species range, and did not investigate evolutionary transitions between sexual systems. Lycium californicum occurs in arid regions on offshore islands and mainland regions in the south-western United States and Mexico, motivating a more comprehensive analysis of intraspecific variation in sexual system and cytotype across the full range of this species. METHODS: Sexual system (dimorphic vs. cosexual) was determined for 34 populations across the geographical range of L. californicum using field observations of pollen production, and was confirmed using morphological measurements and among-plant correlations of primary sexual traits. Ploidy was inferred using flow cytometry in 28 populations. DNA sequence data from four plastid and two nuclear regions were used to reconstruct relationships among populations and to map transitions in sexual system and ploidy. KEY RESULTS: Lycium californicum is monophyletic, ancestrally diploid and cosexual, and the association of gender dimorphism and polyploidy appears to have two evolutionary origins in this species. Compared with cosexual populations, dimorphic populations had bimodal anther size distributions, negative correlations between male and female floral traits, and larger coefficients of variation for primary sexual traits. Flow cytometry confirmed tetraploidy in dimorphic populations, whereas cosexual populations were diploid. CONCLUSIONS: Tetraploidy and gender dimorphism are perfectly correlated in L. californicum, and the distribution of tetraploid-dimorphic populations is restricted to populations in Arizona and the Baja California peninsula. The analysis suggests that tetraploidy and dimorphism likely established in Baja California and may have evolved multiple times. PMID- 26546376 TI - C-arm as intraoperative control in reduction of isolated zygomatic arch fractures: a randomized clinical trial. AB - PURPOSE: Isolated zygomatic arch fractures (IZAFs) are habitually reduced at a distance, via a temporal approach. Open reductions are not recommended due to the associated morbidity and complications. However, performing closed reductions makes it difficult to determine whether it was done satisfactorily. This study aims to determine whether the acquisition of intraoperative images with a C-arm to evaluate IZAF reductions is a useful technique in treating such fractures. METHODS: Our hypothesis is that acquiring intraoperative images with a C-arm reduces the need for a second surgery. Between 2009 and 2012, 50 patients who were diagnosed with IZAF requiring surgery were randomly distributed into two groups: 25 patients were in the experimental group, where fracture reduction was performed and immediately corroborated intraoperatively for an adequate result using a C-arm, and 25 patients were assigned to a control group where the fracture reduction was controlled with post-surgery imaging. RESULTS: The results did not reveal significant differences between both groups (p = 0.5). Nevertheless, the experimental group had the advantage of being able to immediately reduce the fracture again if the result was unsatisfactory. CONCLUSIONS: Despite the fact that the results are not statistically significant (p = 0.5), the authors recommend undertaking an intraoperative imaging analysis in areas where we are not certain of the reduction. PMID- 26546377 TI - The gamma-glutamyl transpeptidase-to-platelet ratio as a predictor of liver fibrosis in patients co-infected with HBV and HIV. PMID- 26546378 TI - Canopy leaf area of a mature evergreen Eucalyptus woodland does not respond to elevated atmospheric [CO2] but tracks water availability. AB - Canopy leaf area, quantified by the leaf area index (L), is a crucial driver of forest productivity, water use and energy balance. Because L responds to environmental drivers, it can represent an important feedback to climate change, but its responses to rising atmospheric [CO2] and water availability of forests have been poorly quantified. We studied canopy leaf area dynamics for 28 months in a native evergreen Eucalyptus woodland exposed to free-air CO2 enrichment (the EucFACE experiment), in a subtropical climate where water limitation is common. We hypothesized that, because of expected stimulation of productivity and water use efficiency, L should increase with elevated [CO2]. We estimated L from diffuse canopy transmittance, and measured monthly leaf litter production. Contrary to expectation, L did not respond to elevated [CO2]. We found that L varied between 1.10 and 2.20 across the study period. The dynamics of L showed a quick increase after heavy rainfall and a steady decrease during periods of low rainfall. Leaf litter production was correlated to changes in L, both during periods of decreasing L (when no leaf growth occurred) and during periods of increasing L (active shedding of old foliage when new leaf growth occurred). Leaf lifespan, estimated from mean L and total annual litter production, was up to 2 months longer under elevated [CO2] (1.18 vs. 1.01 years; P = 0.05). Our main finding that L was not responsive to elevated CO2 is consistent with other forest FACE studies, but contrasts with the positive response of L commonly predicted by many ecosystem models. PMID- 26546379 TI - Extremely Preterm Born Children at Very High Risk for Developing Autism Spectrum Disorder. AB - This study aimed to provide a more comprehensive picture of the prevalence of autism spectrum disorder (ASD) in a geographic cohort of extremely preterm born adolescents by using established diagnostic instruments in addition to screening instruments. 53 participants passed a screening procedure with two screening instruments and a diagnostic evaluation with a semi-structured assessment and a parent interview. 28 % of the adolescents had a community based clinical diagnosis of ASD. When research diagnoses were also taken into account, this rate increased to 40 %. Intellectual disability, language impairment and behavioural difficulties are characteristic for these children with ASD. This study is to our knowledge the first to use ASD-specific diagnostic instruments to confirm ASD diagnoses in extremely preterm born children in early adolescence. The study expands findings of previous research and raises the need for follow-up into late childhood and early adolescence. PMID- 26546380 TI - The necessity of conducting a comprehensive literature review within low-income countries. PMID- 26546382 TI - Lactococcus nasutitermitis sp. nov. isolated from a termite gut. AB - Bacterial strain M19T was isolated from the gut of a wood-feeding termite, Nasutitermes hainanensis. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain M19T was related to members of the genus Lactococcus, with sequence similarities ranging from 84.8 to 95.5 %. Comparison of housekeeping gene ropB sequences revealed that strain M19T was well separated from Lactococcus fujiensis JCM 16395T and Lactococcus hircilactis 117T. The isolate was Gram-stain positive, catalase-negative and non-motile. Cells were coccoid or ovoid-shaped, and occurred singly, in pairs or as short chains. Growth of strain M19T occurred at 10-40 degrees C and at pH 5.0-7.5. The DNA G+C content of strain M19T was 39.6 mol% and the major fatty acids were C16 : 0, cyclo-C19 : 0omega8c, C18 : 1omega9c, summed feature 7 and summed feature 8. Based on the phylogenetic, chemotaxonomic and phenotypic data presented, strain M19T represents a novel species of the genus Lactococcus, for which the name Lactococcus nasutitermitis sp. nov. is proposed. The type strain is M19T ( = CGMCC 1.15204T = NBRC 111537T). PMID- 26546383 TI - Breast Background Parenchymal Enhancement on Screening Magnetic Resonance Imaging in Women Who Received Chest Radiotherapy for Childhood Hodgkin's Lymphoma. AB - RATIONALE AND OBJECTIVES: Breast magnetic resonance imaging (MRI) is recommended for the screening of women with a history of chest radiotherapy and consequent increased breast cancer risk. The purpose of this study was to evaluate the impact of prior chest radiotherapy on breast tissue background parenchymal enhancement (BPE) at screening breast MRI. MATERIALS AND METHODS: A departmental database was reviewed to identify asymptomatic women with either a history of chest radiotherapy for Hodgkin's lymphoma or age-matched controls who underwent screening breast MRI between 2009 and 2013. MRI studies were analyzed on an automated breast MRI viewing platform to calculate breast BPE and breast density. RESULTS: A total of 61 cases (mean age 41.6 +/- 6.75 years) and 61 controls (mean age 40.8 +/- 6.99 years) were included. The age of patients at the time of chest radiotherapy was 22.6 +/- 8.17 years. Screening MRI was performed 19.0 +/- 7.43 years after chest radiotherapy. BPE was significantly higher in patients who received chest radiotherapy (50% vs. 37%, P <0.01). A weak to moderate positive correlation (r > 0.3; P < 0.03) was found between BPE and number of years post radiotherapy. There was a trend toward significant difference between the two groups in the correlation of BPE and age (P = 0.05). Breast density was not significantly different between the two groups. CONCLUSIONS: BPE is significantly greater in women who receive chest radiotherapy for childhood Hodgkin's lymphoma, and unexpectedly, it positively correlates with the number of years passed after radiation therapy. Long-term biological effects of radiation therapy on breast parenchyma need further research. PMID- 26546381 TI - Evaluation of Simulated Clinical Breast Exam Motion Patterns Using Marker-Less Video Tracking. AB - OBJECTIVE: This study investigates using marker-less video tracking to evaluate hands-on clinical skills during simulated clinical breast examinations (CBEs). BACKGROUND: There are currently no standardized and widely accepted CBE screening techniques. METHODS: Experienced physicians attending a national conference conducted simulated CBEs presenting different pathologies with distinct tumorous lesions. Single hand exam motion was recorded and analyzed using marker-less video tracking. Four kinematic measures were developed to describe temporal (time pressing and time searching) and spatial (area covered and distance explored) patterns. RESULTS: Mean differences between time pressing, area covered, and distance explored varied across the simulated lesions. Exams were objectively categorized as either sporadic, localized, thorough, or efficient for both temporal and spatial categories based on spatiotemporal characteristics. The majority of trials were temporally or spatially thorough (78% and 91%), exhibiting proportionally greater time pressing and time searching (temporally thorough) and greater area probed with greater distance explored (spatially thorough). More efficient exams exhibited proportionally more time pressing with less time searching (temporally efficient) and greater area probed with less distance explored (spatially efficient). Just two (5.9 %) of the trials exhibited both high temporal and spatial efficiency. CONCLUSIONS: Marker-less video tracking was used to discriminate different examination techniques and measure when an exam changes from general searching to specific probing. The majority of participants exhibited more thorough than efficient patterns. APPLICATION: Marker less video kinematic tracking may be useful for quantifying clinical skills for training and assessment. PMID- 26546384 TI - Experience and efficacy of surgery for retaining viable subcutaneous tissue in extensive full-thickness burns. AB - BACKGROUND AND AIM: For adult patients with extensive full-thickness burns (EFTB), a fascial excision is mostly used but it causes a very significant deformity. This study aims to summarize experience and efficacy of surgery for retaining viable subcutaneous tissue in EFTB. METHOD: Clinical data were reviewed for 31 consecutive adult patients with full-thickness burn (FTB) over 70% total body surface area (TBSA) and undergoing first tangential excision and skin grafting on subcutaneous tissue wound (TESGSTW) within 7 days post burn at our burn center between 2002 and 2013. RESULTS: Average age, total burn area, and FTB area of 31 patients were 32.4 +/- 12.8 years, 89.0 +/- 6.2% and 80.4 +/- 7.6% TBSA, respectively. Of these, 80.6% combined with inhalation injury and 71.0% supervened early shock. Eighteen patients who survived (58.1%) totally underwent 121 times of surgery, of which TESGSTW and autologous skin grafting were 41 and 88 times, respectively. Their average time and area of first tangential excision was 4.1 +/- 0.6 days post burn and 33.8 +/- 7.6% TBSA, respectively, and accumulated tangential excision area was 58.4 +/- 10.8% TBSA. In 39 times of TESGSTW within 14 days post burn, cryopreserved alloskin or fresh young pigskin was applied on 84.6%, and average time and take rate of autologous skin grafting instead of grafted alloskin or xenoskin was 14.6 +/- 0.7 days and 89.5 +/- 1.4%, respectively. Scalp was the main donor site for autologous skin, especially microskin grafting. Systemic wound healing time roughly was 67.3 +/- 1.9 days post burn, meanwhile, viable subcutaneous tissue was retained. Healed wounds were plump, and their extensibility and sensitivity were better by follow-up. CONCLUSION: The surgical treatment in EFTB is practicable and effective. PMID- 26546385 TI - Scar outcome of children with partial thickness burns: A 3 and 6 month follow up. AB - INTRODUCTION: There is a paucity of research investigating the scar outcome of children with partial thickness burns. The aim of this study was to assess the scar outcome of children with partial thickness burns who received a silver dressing acutely. METHOD: Children aged 0-15 years with an acute partial thickness burn, <=10% TBSA were included. Children were originally recruited for an RCT investigating three dressings for partial thickness burns. Children were assessed at 3 and 6 months after re-epithelialization. 3D photographs were taken of the burn site, POSAS was completed and skin thickness was measured using ultrasound imaging. RESULTS: Forty-three children returned for 3 and 6 month follow-ups or returned a photo. Days to re-epithelialization was a significant predictor of skin/scar quality at 3 and 6 months (p<0.01). Patient-rated color and observer-rated vascularity and pigmentation POSAS scores were comparable at 3 months (color vs. vascularity 0.88, p<0.001; color vs. pigmentation 0.64, p<0.001), but patients scored higher than the observer at 6 months (color vs. vascularity 0.57, p<0.05; color vs. pigmentation 0.15, p=0.60). Burn depth was significantly correlated with skin thickness (r=0.51, p<0.01). Hypopigmentation of the burn site was present in 25.8% of children who re-epithelialized in <= 2 weeks. CONCLUSION: This study has provided information on outcomes for children with partial thickness burns and highlighted a need for further education of this population. PMID- 26546386 TI - Interactive gaming consoles reduced pain during acute minor burn rehabilitation: A randomized, pilot trial. AB - INTRODUCTION: Interactive gaming consoles (IGCs) have been used successfully in rehabilitation settings as an adjunct to conventional exercise for restoring or maintaining active function and augmenting pharmacological analgesia. AIM: The objective of this pilot study was to assess if adjunctive use of the Nintendo Wii IGC was of benefit to acute burn patients. METHOD: This was a randomized, controlled trial. The intervention group received routine rehabilitation in addition to up to 5 days of twice daily, 20-30 min of exercise using the Nintendo Wii IGC. The control group received routine rehabilitation exercise therapy. RESULTS: A total of 22 subjects were recruited and randomized by location of burn to intervention and control groups. Pain scores were significantly improved in the intervention group (r(2)=1.18; 95%CI -0.584 to -0.298, p=0.019) as indicated by a 17% greater drop in the pre-post-study pain compared to controls. Fear avoidance and ROM measurements were not statistically different between the groups. CONCLUSION: The Nintendo Wii IGC was associated with a greater reduction in pain, particularly in those with higher levels of pain at baseline. PMID- 26546387 TI - Effects of ethinylestradiol-cyproterone acetate vs. pioglitazone-flutamide metformin on plasma FGF21 levels in adolescent girls with androgen excess. PMID- 26546388 TI - Exploring person-centredness in emergency departments: A literature review. AB - Person-centred approaches to care delivery have been increasingly promoted in international policy and strategy, but despite this there is evidence of failings within healthcare systems that negatively impact on the care experience for patients and staff. This paper explores the international literature on person centredness within emergency departments (EDs). The Person-centred Practice Framework was used as the underpinning theoretical framework. This theory contends that staff must possess certain attributes to manage the care environment appropriately to deliver effective care processes in order to achieve effective person-centred outcomes for patients and staff. An initial search of the literature identified no relevant papers that discussed person-centredness as a concept within EDs. A further search using terms drawn from a definition of person-centredness revealed literature that reflected components of person centredness. Themes that emerged included medical-technical intervention, a culture of worthiness, managing the patient journey, nurse/doctor relationships, patients' and relatives' experience of care, and ED as a stressful environment. The themes can be mapped onto the Person-centred Practice Framework, suggesting that components of person-centred practice have emerged from studies in a fragmented fashion, without consideration of person-centredness as a whole within an ED context. PMID- 26546389 TI - Screening for Pediatric Blunt Cerebrovascular Injury: Review of Literature and a Cost-Effectiveness Analysis. AB - BACKGROUND: Timely and accurate screening for pediatric blunt cerebrovascular injury (BCVI) is important in order to administer appropriate anticoagulation therapy thus preventing stroke. The recommended criteria for screening in children are not clear. We performed a systematic review of the literature for screening and management of BCVI in children and designed a cost-effectiveness analysis in order to determine the optimal strategy for managing pediatric BCVI from a societal perspective. METHODS: Comprehensive review of studies citing BCVI in pediatric patients was carried out with data extraction and compilation. An economic evaluation of 5 possible screening strategies was performed by designing a decision tree over a 1-year horizon using parameters derived from literature review. Base case calculations were made to compare cost effectiveness for each strategy. Monte Carlo simulation and extensive sensitivity analyses were performed to examine the robustness of the conclusion against key variables. RESULTS: Selective anticoagulation therapy in patients with high-risk factors was found to be the most cost-effective strategy and selective computed tomography angiography (CTA) in high-risk patients was the optimal imaging strategy. This conclusion was corroborated by a Monte Carlo simulation of 10,000 iterations. In all sensitivity analyses, selective anticoagulation and selective CTA continue to be the optimal strategy until the risk of anticoagulation complications rises above 3.9%. CONCLUSIONS: Our study demonstrated selective CTA to be the optimal imaging strategy in order to assess BCVI in children. Further studies are needed for more clearly defined screening criteria. PMID- 26546390 TI - N-Heterocyclic Carbene Catalyzed Dynamic Kinetic Resolution of Pyranones. AB - The dynamic kinetic resolution of 6-hydroxypyranones with enals or alkynals through an asymmetric redox esterification is catalyzed by a chiral N heterocyclic carbene. The resulting esters are obtained in good to high yields and with high levels of enantio- and diastereocontrol. The reaction products are further derivatized to obtain functionalized sugar derivatives and natural products. PMID- 26546391 TI - Local full-thickness skin graft to cover the radial forearm free flap donor site. PMID- 26546392 TI - Continuous postoperative pain control using a multiple-hole catheter after iliac bone grafting: comparison between ropivacaine and levobupivacaine. AB - The aim of this study was to compare the analgesic effects of ropivacaine and levobupivacaine in continuous infiltration anaesthesia delivered via a multiple hole catheter for the purpose of postoperative analgesia after iliac bone grafting. Thirty-four patients scheduled for iliac bone grafting in the maxillofacial region participated in this study. The patients were randomized to a ropivacaine group (Ropi group) and a levobupivacaine group (Levo group). After harvesting the iliac bone for grafting, a multiple-hole catheter was placed on the periosteum of the iliac bone. When surgery was completed, continuous administration was started at 4 ml/h of 0.2% ropivacaine (Ropi group) or 0.25% levobupivacaine (Levo group). Pain was evaluated in the recovery room and at 4h after surgery, as well as at 9:00 and 18:00 on postoperative days 1, 2, and 3, using a visual analogue scale. Side effects were also recorded. No significant difference in the visual analogue scale scores at rest or in motion was observed between the two groups. In addition, there were no side effects in the two groups. Both 0.2% ropivacaine and 0.25% levobupivacaine provided comparable analgesic effects in continuous infiltration anaesthesia delivered via a multiple hole catheter after iliac bone grafting. PMID- 26546393 TI - Immediate implant placement in fresh sockets versus implant placement in healed bone for full-arch fixed prostheses with conventional loading. AB - This retrospective study assessed the success of immediate and non-immediate implants installed in patients undergoing planned extraction of all remaining teeth and rehabilitation with implant-supported full fixed prostheses. Patients in need of dental implants for full fixed prostheses to replace teeth extracted in the maxilla and mandible were included in this study. Dental implants were installed in the same surgical procedure, immediately at the extraction site, or in healed bone. Implant success, complications, and failures were recorded during follow-up. Forty-one patients with 512 implants were included in the study. Healing progressed uneventfully for 501 installed implants, but nine implants were lost in the non-immediate group and two were lost in the immediate group, during a mean follow-up of 44.9 months. All failures in both groups were observed in the maxilla. The success rate was the same in both groups, at 97.8%. This retrospective analysis showed that with thorough patient evaluation, the extraction of all residual teeth and implant installation in a single surgical procedure is a safe and predictable treatment modality for the successful rehabilitation of the edentulous patient with a fixed prosthesis. PMID- 26546394 TI - Mid Staffordshire trust pleads guilty to health and safety breaches. PMID- 26546395 TI - Change and stability in depressive symptoms in young adults with type 1 diabetes. AB - This study examined inter-individual differences in depressive symptom development in young adults with type 1 diabetes. Individuals with persistent depressive symptoms were at risk for suboptimal development in terms of illness perceptions, illness functioning, and self-esteem. Individuals reporting no/minimal depressive symptoms over time were characterized by the most optimal development. PMID- 26546396 TI - On the problem of type 2 diabetes-related mortality in the Canary Islands, Spain. The DARIOS Study. AB - AIMS: To compare diabetes-related mortality rates and factors associated with this disease in the Canary Islands compared with other 10 Spanish regions. METHODS: In a cross-sectional study of 28,887 participants aged 35-74 years in Spain, data were obtained for diabetes, hypertension, dyslipidemia, obesity, insulin resistance (IR), and metabolic syndrome. Healthcare was measured as awareness, treatment and control of diabetes, dyslipidemia, and hypertension. Standardized mortality rate ratios (SRR) were calculated for the years 1981 to 2011 in the same regions. RESULTS: Diabetes, obesity, and hypertension were more prevalent in people under the age of 64 in the Canary Islands than in Spain. For all ages, metabolic syndrome and insulin resistance (IR) were also more prevalent in those from the Canary Islands. Healthcare parameters were similar in those from the Canary Islands and the rest of Spain. Diabetes-related mortality in the Canary Islands was the highest in Spain since 1981; the maximum SRR was reached in 2011 in men (6.3 versus the region of Madrid; p<0.001) and women (9.5 versus Madrid; p<0.001). Excess mortality was prevalent from the age of 45 years and above. CONCLUSIONS: Diabetes-related mortality is higher in the Canary Islands population than in any other Spanish region. The high mortality and prevalence of IR warrants investigation of the genetic background associated with a higher incidence and poor prognosis for diabetes in this population. The rise in SRR calls for a rapid public health policy response. PMID- 26546397 TI - IL-1alpha induces angiogenesis in brain endothelial cells in vitro: implications for brain angiogenesis after acute injury. AB - Inflammation is a major contributor to neuronal injury and is associated with poor outcome after acute brain injury such as stroke. The pro-inflammatory cytokine interleukin (IL)-1 is a critical regulator of cerebrovascular inflammation after ischemic injury, mainly through action of both of its isoforms, IL-1alpha and IL-1beta, at the brain endothelium. In contrast, the differential action of these ligands on endothelial activation and post-stroke angiogenesis is largely unknown. Here, we demonstrate that IL-1alpha is chronically elevated in the brain after experimental stroke suggesting that it is present during post-stroke angiogenic periods. Furthermore, we demonstrate that IL-1alpha is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells in vitro. Using brain endothelial cell lines, we found that IL-1alpha was significantly more potent than IL-1beta at inducing endothelial cell activation, as measured by expression of the pro angiogenic chemokine CXCL-1. IL-1alpha also induced strong expression of the angiogenic mediator IL-6 in a concentration-dependent manner. Furthermore, IL 1alpha induced significant proliferation and migration of endothelial cells, and promoted formation of tube-like structures that are established key hallmarks of angiogenesis in vitro. Finally, all of those responses were blocked by the IL-1 receptor antagonist (IL-1RA). In conclusion, our data highlights a potential new role for IL-1 in brain repair mechanisms and identifies IL-1alpha as a potential new therapy to promote post-stroke angiogenesis. Inflammation is a major contributor to neuronal injury and is associated with poor outcome after neurotrauma. We demonstrate that cytokine IL-1alpha is chronically elevated in the brain after experimental stroke suggesting that it is present chronically post-stroke. We demonstrate that IL-1alpha is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells. Our data highlights a new role for IL-1 in brain repair mechanisms and identifies IL 1alpha as a potential therapy to promote post-stroke angiogenesis. PMID- 26546398 TI - The effect of weirs on nutrient concentrations. AB - The removal of a weir in 1999 from the River Nidd in Yorkshire, UK, was assessed in terms of its impact on in-stream nitrate removal along a 15.8 km long stretch of river. Models of channel hydraulics and denitrification quantified the impact on an annual basis, using, as inputs, river flow, water temperature, water quality data and cross-section geometry collected both before and after the weir was removed. To remove the confounding influences of year-specific conditions, two counterfactual simulations were set up whereby the pre-removal configuration was driven by data from the post-removal period (and vice versa). Results revealed the removal of the weir to have reduced the annual fraction of the upstream nitrate load being retained along the stretch by 2.6% (i.e. 812 kg) and 1.8% (382 kg) for the years 1997 and 2000 respectively. Differences resulting from the presence or absence of the weir were most marked during low flow summer conditions. PMID- 26546399 TI - The experience and impact of traumatic perinatal event experiences in midwives: A qualitative investigation. AB - BACKGROUND: Through their work midwives may experience distressing events that fulfil criteria for trauma. However, there is a paucity of research examining the impact of these events, or what is perceived to be helpful/unhelpful by midwives afterwards. OBJECTIVE: To investigate midwives' experiences of traumatic perinatal events and to provide insights into experiences and responses reported by midwives with and without subsequent posttraumatic stress symptoms. DESIGN: Semi-structured telephone interviews were conducted with a purposive sample of midwives following participation in a previous postal survey. METHODS: 35 midwives who had all experienced a traumatic perinatal event defined using the Diagnostic and Statistical Manual of Mental Disorders (version IV) Criterion A for posttraumatic stress disorder were interviewed. Two groups of midwives with high or low distress (as reported during the postal survey) were purposefully recruited. High distress was defined as the presence of clinical levels of PTSD symptomatology and high perceived impairment in terms of impacts on daily life. Low distress was defined as any symptoms of PTSD present were below clinical threshold and low perceived life impairment. Interviews were analysed using template analysis, an iterative process of organising and coding qualitative data chosen for this study for its flexibility. An initial template of four a priori codes was used to structure the analysis: event characteristics, perceived responses and impacts, supportive and helpful strategies and reflection of change over time codes were amended, integrated and collapsed as appropriate through the process of analysis. A final template of themes from each group is presented together with differences outlined where applicable. RESULTS: Event characteristics were similar between groups, and involved severe, unexpected episodes contributing to feeling 'out of a comfort zone.' Emotional upset, self blame and feelings of vulnerability to investigative procedures were reported. High distress midwives were more likely to report being personally upset by events and to perceive all aspects of personal and professional lives to be affected. Both groups valued talking about the event with peers, but perceived support from senior colleagues and supervisors to be either absent or inappropriate following their experience; however, those with high distress were more likely to endorse this view and report a perceived need to seek external input. CONCLUSION: Findings indicate a need to consider effective ways of promoting and facilitating access to support, at both a personal and organisational level, for midwives following the experience of a traumatic perinatal event. PMID- 26546400 TI - Natural Products as Source of Therapeutics against Parasitic Diseases. AB - An end to suffering: Parasitic infections with protozoa and worms cause unimaginable misery, in particular in the tropics. Fortunately, natural products, such as the antimalarial artemisinin (1) and the anthelmintic avermectin (2) were discovered and developed into therapeutics. These major achievements now culminated in the 2015 Nobel Prize for Medicine. PMID- 26546401 TI - Problems in biology with many scales of length: Cell-cell adhesion and cell jamming in collective cellular migration. AB - As do all things in biology, cell mechanosensation, adhesion and migration begin at the scale of the molecule. Collections of molecules assemble to comprise microscale objects such as adhesions, organelles and cells. And collections of cells in turn assemble to comprise macroscale tissues. From the points of view of mechanism and causality, events at the molecular scale are seen most often as being the most upstream and, therefore, the most fundamental and the most important. In certain collective systems, by contrast, events at many scales of length conspire to make contributions of equal importance, and even interact directly and strongly across disparate scales. Here we highlight recent examples in cellular mechanosensing and collective cellular migration where physics at some scale bigger than the cell but smaller than the tissue - the mesoscale - becomes the missing link that is required to tie together findings that might otherwise seem counterintuitive or even unpredictable. These examples, taken together, establish that the phenotypes and the underlying physics of collective cellular migration are far richer than previously anticipated. PMID- 26546402 TI - Management of malignant pleural mesothelioma: a French multicenter retrospective study (GFPC 0802 study). AB - BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. METHODS: Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. RESULTS: Four hundred and six patients were included in 37 sites: mean age 68.9 +/- 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioid type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. CONCLUSIONS: The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials. PMID- 26546403 TI - Magnesium Sulfate Plus Lidocaine Reduces Propofol Injection Pain: A Double-blind, Randomized Study. AB - PURPOSE: Propofol injection can cause distressing pain, and no method can inhibit it completely. Neither lidocaine nor magnesium sulfate (MgSO4) was sufficient to prevent pain from the injection of propofol. This prospective, double-blind, placebo-controlled study was designed to investigate the efficacy of the MgSO4 plus lidocaine on suppressing propofol injection pain. METHODS: Three hundred women received 300 mg MgSO4 (Group M), 40 mg lidocaine (Group L), or 300 mg MgSO4 plus 40 mg lidocaine (Group M+L). This was followed by administration of 50 mg propofol. Pain scores, behavior-related responses, and diameter of the vein were recorded following the injection of propofol. FINDINGS: Patients in Group M + L had lower pain scores. Patients' behavior-related responses in Group M + L were also better compared with the other groups. There were no differences in pain scores between Group L and Group M. The target vein diameter change in Group M and Group M + L was more obvious than in Group L. IMPLICATIONS: Administration of 300 mg MgSO4 plus 40 mg lidocaine reduces propofol injection pain very well. No complications were observed in the treatment groups. PMID- 26546404 TI - Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services. AB - PURPOSE: More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. METHODS: The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. FINDINGS: All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. IMPLICATIONS: The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. PMID- 26546405 TI - Pharmacokinetics of a New Orally Disintegrating Tablet Formulation of Aripiprazole 15 mg Administered Without Water in Healthy Middle-aged Korean Subjects. AB - PURPOSE: The main objective of this study was to compare the pharmacokinetic properties and relative bioavailability of two 15-mg aripiprazole formulations (an orally disintegrating tablet [ODT] as the test drug and a conventional tablet as the reference drug) in healthy middle-aged Korean subjects. METHODS: This study was conducted in a population of healthy middle-aged Korean subjects as a randomized, open-label, single-dose, 2-sequence, 2-period crossover trial. After administration of a single dose of a 15-mg aripiprazole standard tablet with 240 mL water or an aripiprazole 15-mg ODT without water, blood samples were collected at specific time intervals from 0 to 240 hours. Concentrations of aripiprazole in plasma were analyzed by using a LC-MS/MS method of detection. Data on the pharmacokinetic parameters were recorded, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using an ANOVA model. FINDINGS: Thirty-nine healthy middle aged Korean subjects were enrolled (mean age, 52.7 years; mean height, 167 cm; mean weight, 67.6 kg); 33 participants completed the study (29 male subjects and 4 female subjects). The 90% CIs of the geometric means ratio (test drug/reference drug) of Cmax, AUC0-last, and AUC0-infinity values were 0.95 to 1.14, 0.98 to 1.09, and 0.97 to 1.08, respectively. All of the subjects who experienced adverse events recovered without sequelae, and no serious adverse events were observed. IMPLICATIONS: The aripiprazole pharmacokinetics was similar for the ODT and standard tablet of 15-mg aripiprazole in these healthy middle-aged Korean subjects. The aripiprazole ODT formulation is therefore expected to offer a convenient alternative for patients who have difficulty swallowing tablets without water. The study was registered at http://cris.nih.go.kr (registration number: KCT0001677). PMID- 26546406 TI - PpiA antigen specific immune response is a potential biomarker for latent tuberculosis infection. AB - One third of the world's population is estimated to harbour latent tuberculosis infection (LTBI). Around 10% of them have the life time risk of developing active tuberculosis (PTB). Currently there is no gold standard test for identifying LTBI. Therefore identification of specific markers for LTBI will help as to develop a test specific for LTBI. Earlier, in our immunoproteomic analysis, we found that peptidyl-prolyl cis-trans isomerase A (PpiA) protein-containing fractions induced significantly higher interferon-gamma (IFN-gamma) response in LTBI than in PTB. Immunological characterisation of recombinant PpiA protein was carried out in the current study. We have studied 10 cytokines and 2 chemokine responses against PpiA and standard antigens such as early secretory antigenic target-6 (ESAT-6) and culture filtrate antigen-10 (CFP-10). In healthy household contacts (HHC), all the tested antigens induced significantly higher levels of IFN-gamma and Interlukin-8 (IL-8) compared with those in PTB. PpiA-specific IL 12p40 response was significantly increased in HHC compared with that in PTB. PpiA antigen-specific IFN-gamma and IL-12p40 both showed 86% positivity in HHC, whereas in PTB, they showed 20% and 38% positivity, respectively. In terms of IFN gamma/TNF-alpha ratio, PpiA displayed 86% (30/35) positivity in HHC and 18% (7/39) positivity in PTB. In summary we found that PpiA-specific IFN-gamma and IFN-gamma/TNF-alpha ratio response were specific biomarkers for LTBI identification. PMID- 26546407 TI - New Insights into Eosinophilic Otitis Media. AB - Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM. PMID- 26546409 TI - Reproducibility of kinematic measures of the thoracic spine, lumbar spine and pelvis during fast running. AB - This study evaluated the reproducibility of the angular rotations of the thoracic spine, lumbar spine, pelvis and lower extremity during running. In addition, the study compared kinematic reproducibility between two methods for calculating kinematic trajectories: a six degrees of freedom (6DOF) approach and a global optimisation (GO) approach. With the first approach segments were treated independently, however with GO approach joint constraints were imposed to stop translation of adjacent segments. A total of 12 athletes were tested on two separate days whilst running over ground at a speed of 5.6ms(-1). The results demonstrated good between-day reproducibility for most kinematic parameters in the frontal and transverse planes with typical angular errors of 1.4-3 degrees . Acceptable repeatability was also found in the sagittal plane. However, in this plane, although kinematic waveform shape was preserved between testing session, there were sometimes shifts in curve offset which lead to slightly higher angular errors, typically ranging from 1.9 degrees to 3.5 degrees . In general, the results demonstrated similar levels of reproducibility for both computational approaches (6DOF and, GO) and therefore suggest that GO may not lead to improved kinematic reproducibility during running. PMID- 26546408 TI - Distinct innate responses are induced by attenuated Salmonella enterica serovar Typhimurium mutants. AB - Upon bacterial infection the host cells generate a wide variety of cytokines. Genetic attenuation of bacterial physiological pathogens can be accomplished not only by disruption of normal bacterial processes, but also by the loss of the ability to redirect the host immune system. We examined nine attenuated Salmonella Typhimurium mutants for their ability to replicate as well as the cytokines produced after infection of Bone Marrow Derived Macrophages (BMDM). Infection of BMDM with attenuated Salmonella mutants led to host cytokine patterns distinct from those that followed WT infection. Surprisingly, each bacterial mutant had a unique cytokine signature. Because some of the mutants induced an IL-10 response not seen in WT, we examined the role of IL-10 on Salmonella replication. Surprisingly, addition of IL-10 before or concurrent with infection restricted growth of WT Salmonella in BMDM. Bacterial attenuation is not a single process and results in attenuated host responses, which result in unique patterns for each attenuated mutants. PMID- 26546410 TI - Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR. AB - Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC% content changed from 56% to 58%. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa. PMID- 26546411 TI - p21 deficiency is susceptible to osteoarthritis through STAT3 phosphorylation. AB - INTRODUCTION: Osteoarthritis (OA) is a multifactorial disease, and recent studies have suggested that cell cycle-related proteins play a role in OA pathology. p21 was initially identified as a potent inhibitor of cell cycle progression. However, it has been proposed that p21 is a regulator of transcription factor activity. In this study, we evaluated the role of p21 in response to biomechanical stress. METHODS: Human chondrocytes were treated with p21-specific small interfering RNA (siRNA), and cyclic tensile strain was introduced in the presence or absence of a signal transducer and activator of transcription 3 (STAT3)-specific inhibitor. Further, we developed an in vivo OA model in a p21 knockout background for in vivo experiments. RESULTS: The expression of matrix metalloproteinase (MMP13) mRNA increased in response to cyclic tensile strain following transfection with p21 siRNA, whereas the expression of aggrecan was decreased. Phospho-STAT3 and MMP-13 protein levels increased following downregulation of p21, and this was reversed by treatment with a STAT3 inhibitor. p21-deficient mice were susceptible to OA, and this was associated with increased STAT3 phosphorylation, elevated MMP-13 expression, and elevation of synovial inflammation. The expression of p21 mRNA was decreased and phosphorylation of STAT3 was elevated in human OA chondrocytes. CONCLUSIONS: The lack of p21 has catabolic effects by regulation of aggrecan and MMP-13 expression through STAT3 phosphorylation in the cartilage tissue. p21 may function as a regulator of transcriptional factors other than the inhibitor of cell cycle progression in the cartilage tissue. Thus, the regulation of p21 may be a therapeutic strategy for the treatment of OA. PMID- 26546413 TI - Influence of molecular weight of PEG chain on interaction between streptavidin and biotin-PEG-conjugated phospholipids studied with QCM-D. AB - Poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) derivatives spontaneously incorporate into lipid bilayer membranes, thus, they are useful for immobilizing bioactive substances onto cell surfaces. Here, we investigated how the density and molecular weight of PEG molecules influenced immobilization and cellular uptake of a bioactive substance. We analyzed how three biotin-PEG-lipids (1k, 5k, and 40k, with PEG molecular weights: 1kD, 5kD, and 40kD, respectively) interacted with streptavidin on a surface attached to a quartz crystal microbalance with dissipation (QCM-D). We found that the volume excluded by 1k PEG could not effectively prevent adsorption of bovine serum albumin (BSA). In contrast, 5k PEG chains could completely prevent protein adsorption. However, due to strong static repulsion, 40k PEG chains could not be packed at high density. Thus, BSA migrated between PEG chains, and adsorption was not effectively prevented. When streptavidin was added, it bound to multiple neighboring sites on 1k and 5k biotin-PEG-lipids, which reduced chain viscoelasticity. In contrast, streptavidins bound at a one-to-one stoichiometry with the 40k biotin-PEG-lipids, which increased chain viscoelasticity. However, differences in PEG viscoelasticity and PEG molecular weights did not influence cellular uptake of immobilized streptavidin. Therefore, these are not important factors in designing polymers that prevent cellular endocytosis. STATEMENT OF SIGNIFICANCE: Poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) derivatives have been widely used to modify not only liposome surface, but also the surfaces of cells and pancreatic islets for cell transplantation. Since the entire cell surface can be modified with PEG-lipid through hydrophobic interactions, it is a promising approach for improving graft survival in clinical settings. Although the surface modification is protective in the early stages of transplantation, it is important to understand the factors that influence on the cellular uptake. In this study, we examined the influence of the surface density and molecular weights of PEG-lipids on the cellular uptake by QCM-D and cellular experiments. It was found that the differences in viscoelasticity of PEG chain did not affect on the cellular uptake. PMID- 26546414 TI - Short, multiple-stranded beta-hairpin peptides have antimicrobial potency with high selectivity and salt resistance. AB - The beta-hairpin structure has been proposed to exhibit potent antimicrobial properties with low cytotoxicity, thus, multiple beta-hairpin structures have been proved to be highly stable in structures containing tightly packed hydrophobic cores. The aim of this study was to develop peptide-based synthetic strategies for generating short, but effective AMPs as inexpensive antimicrobial agents. Multiple-stranded beta-hairpin peptides with the same beta-hairpin unit, (WRXxRW)n where n=1, 2, 3, or 4 and Xx represent the turn sequence, were synthesized, and their potential as antimicrobial agents was evaluated. Owning to the tightly packed hydrophobic core and paired Trp of this multiple-stranded beta hairpin structure, all the 12-residues peptides exhibited high cell selectivity towards bacterial cells over human red blood cells (hRBCs), and the peptide W2 exhibited stronger antimicrobial activities with the MIC values of 2-8MUM against various tested bacteria. Not only that, but W2 also showed obvious synergy with streptomycin and chloramphenicol against Escherichia coli, and displayed synergy with ciprofloxacin against Staphylococcus aureus with the FICI values ?0.5. Fluorescence spectroscopy and electron microscopy analyses indicated that W2 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Collectively, based on the multiple beta-hairpin peptides, the ability to develop libraries of short and effective peptides will be a powerful approach to the discovery of novel antimicrobial agents. STATEMENT OF SIGNIFICANCE: We successfully screened a peptide W2 ((WRPGRW)2) from a series of multiple-stranded beta-hairpin antimicrobial peptides based on the "S-shaped" motif that induced the formation of a globular structure, and Trp zipper was used to replace the disulfide bonds to reduce the cost of production. This novel structure applied to AMPs improved cell selectivity and salt stability. The findings of this study will promote the development of peptide-based antimicrobial biomaterials. Further exploration of these AMPs will allow for diverse biotechnological and clinical applications such as biomedical coating, food storaging, and animal feeding. PMID- 26546412 TI - Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide. AB - BACKGROUND: Temozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 MUM). METHODS: MGMT expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 MUM. Clonogenic GSC surviving 500 MUM TMZ (GSC-500 MUM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC. RESULTS: The molecular signatures characterized an activation of protective stress responses in GSC-500 MUM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 MUM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 MUM TMZ and GSC-parental to 35 MUM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489). CONCLUSIONS: These data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT. PMID- 26546415 TI - Linear and nonlinear optical waveguiding in bio-inspired peptide nanotubes. AB - Unique linear and nonlinear optical properties of bioinspired peptide nanostructures such as wideband transparency and high second-order nonlinear optical response, combined with elongated tubular shape of variable size and rapid self-assembly fabrication process, make them promising for diverse bio-nano photonic applications. This new generation of nanomaterials of biological origin possess physical properties similar to those of biological structures. Here, we focus on new specific functionality of ultrashort peptide nanotubes to guide light at fundamental and second-harmonic generation (SHG) frequency in horizontal and vertical peptide nanotubes configurations. Conducted simulations and experimental data show that these self-assembled linear and nonlinear optical bio waveguides provide strong optical power confinement factor, demonstrate pronounced directionality of SHG and high conversion efficiency of SHG ~10(-5). Our study gives new insight on physics of light propagation in nanostructures of biological origin and opens the avenue towards new and unexpected applications of these waveguiding effects in bio-nanomaterials both for biomedical nonlinear microscopy imaging recognition and development of novel integrated nanophotonic devices. PMID- 26546416 TI - Neuroprotective effect of allicin in a rat model of acute spinal cord injury. AB - AIMS: This study aims to investigate the effect of allicin on motor functions and histopathologic changes after spinal cord injury and the mechanism underlying its neuroprotective effects. MAIN METHODS: The motor function of rats was evaluated with the Basso, Beattie, and Bresna test. Histopathologic changes were evaluated by hematoxylin and eosin and Nissl staining. Spinal cord oxidative stress markers were determined by measuring glutathione and malondialdehyde content and superoxide dismutase activity using commercial kits. Inflammatory factors were determined by measuring tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 using ELISA assay. Apoptosis was examined using TUNEL staining. The effect of allicin on Nrf2 protein levels and localization was assessed using immunofluorescence staining and Western blotting analysis. KEY FINDINGS: Results demonstrated that allicin accelerated the motor functional recovery and protected neuron damage against spinal cord injury (SCI). SCI-induced oxidative stress, inflammatory response and cell apoptosis in the spinal cord were also prevented by allicin. In addition, we observed that SCI increased Nrf2 nuclear expression, and allicin treatment further increased Nrf2 nuclear translocation in neurons and astrocytes. siRNA-mediated Nrf2 gene knockdown completely blocked the effect of allicin on spinal cord tissue. SIGNIFICANCE: Our finding suggests that allicin promotes the recovery of motor function after SCI in rats, and this effect may be related to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Allicin mediated Nrf2 nuclear translocation may be involved in the protective effect as well. PMID- 26546417 TI - Unique DNA Methylation Patterns in Offspring of Hypertensive Pregnancy. AB - Epigenomic processes are believed to play a pivotal role for the effect of environmental exposures in early life to modify disease risk throughout the lifespan. Offspring of women with hypertensive complications of pregnancy (HTNPREG ) have an increased risk of developing systemic and pulmonary vascular dysfunction in adulthood. In this preliminary report, we sought to determine whether epigenetic modifications of genes involved in the regulation of vascular function were present in HTNPREG offspring. We contrasted DNA methylation and gene expression patterns of peripheral blood mononuclear cells obtained from young male offspring of HTNPREG (n = 5) to those of normotensive controls (n = 19). In HTNPREG offspring we identified six differentially methylated regions (DMRs) including three genes (SMOC2, ARID1B and CTRHC1) relevant to vascular function. The transcriptional activity of ARID1B and CTRCH1 was inversely related to methylation status. HTNPREG offspring had higher systolic pulmonary artery pressure (sPPA ) versus controls. Our findings demonstrate that epigenetic marks are altered in offspring of HTNPREG with a modest elevation of sPPA and introduce novel epigenomic targets for further study. On the basis of these findings we speculate that epigenomic mechanisms may be involved in mediating the effect of HTNPREG to raise the risk of vascular disease later in life. PMID- 26546418 TI - Characterization of 5'UTR of rice ClpB-C/Hsp100 gene: evidence of its involvement in post-transcriptional regulation. AB - Rice (Oryza sativa) ClpB-C (OsClpB-C) protein is expressed upon heat stress in vegetative tissues and constitutively in seeds. We produced stably transformed Arabidopsis plants carrying beta-glucuronidase (Gus) reporter gene downstream to 1-kb OsClpB-C promoter (1kbPro plants). In the 1kbPro plants, expression of Gus transcript and protein followed the expression pattern of OsClpB-C gene in rice plants, i.e., heat induced in vegetative tissues and constitutive in seeds. Next, we produced transgenic Arabidopsis plants containing Gus downstream to 862-bp fragment of OsClpB-C promoter [lacking 138 nucleotides from 3' end of the 5'untranslated region (5'UTR); ?UTR plants). In ?UTR plants, Gus transcript was expressed in heat-inducible manner, but strikingly, Gus protein levels were negligible after heat treatment. However, Gus protein was expressed in ?UTR seedlings at levels comparable to 1kbPro seedlings when recovery treatment of 22 degrees C/2 h was given post heat stress (38 degrees C/15 min). This suggests that 5'UTR of OsClpB-C gene is involved in its post-transcriptional regulation and is an obligate requirement for protein expression during persistent heat stress. Furthermore, the Gus transcript levels were higher in the polysomal RNA fraction in heat-stressed seedlings of 1kbPro plants as compared to ?UTR plants, indicating that 5'UTR aids in assembly of ribosomes onto the Gus transcript during heat stress. Unlike the case of seedlings, Gus protein was formed constitutively in ?UTR seeds at levels comparable to 1kbPro seeds. Hence, the function of 5'UTR of OsClpB-C is dispensable for expression in seeds. PMID- 26546419 TI - Annual incidence rates of herpes zoster among an immunocompetent population in the United States. AB - BACKGROUND: Herpes zoster (HZ), also known as shingles, is a painful and commonly occurring condition in the United States. In spite of a universally recommended vaccine for use in immunocompetent adults aged 60 years and older, HZ continues to impact the American public, and a better understanding of its current incidence is needed. The objective of the current study is to estimate the overall and age- and gender-specific incidence rates (IRs) of HZ among an immunocompetent US population in 2011 following availability of a vaccine. METHODS: Claims data from the Truven Health MarketScan(r) Research databases between 01/01/2011 and 12/31/2011 were extracted. Immunocompetent adult patients, enrolled as of January 1, 2011 were analyzed. The denominator was defined as eligible subjects who were immunocompetent, had no evidence of zoster vaccination, and no diagnosis of HZ (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 053.xx) in the 90 days prior to January 1, 2011. Subjects contributed person-days to the denominator until the occurrence of one of the following events: end of continuous enrollment in the database, a claim for zoster vaccination, diagnosis of HZ or end of the observation period (December 31, 2011). The numerator was defined as enrollees within the denominator file exhibiting evidence of HZ. Annual IRs were calculated for the entire population in the database as well as by gender and age group; standardized IRs were also produced using the 2010 US Census data. RESULTS: The overall annual IR of HZ across all ages was 4.47 per 1000 person-years (95% confidence interval [CI]: 4.44-4.50) which monotonically increased with age from 0.86 (95% CI: 0.84-0.88) for those aged <= 19 to 12.78 (95% CI: 12.49-13.07) for patients >= 80 years. The IR was 8.46 (95% CI: 8.39-8.52) among adults >= 50 years and 10.46 (95% CI: 10.35-10.56) among those aged >= 60 years. Women compared to men had higher HZ incidence (5.25, 95% CI: 5.21-5.29 vs. 3.66, 95% CI: 3.62-3.69) and this was seen across all age groups. When adjusted for age and gender using 2010 US Census data, the annual IR was 4.63 per 1000 person-years (95% CI: 4.61-4.66). CONCLUSIONS: Despite the availability of a vaccine, HZ remains common among immunocompetent adults in the US with incidence rates of HZ observed to increase with age and be higher in women than men. PMID- 26546420 TI - Distribution and Sources of Petroleum Hydrocarbons in Recent Sediments of the Imo River, SE Nigeria. AB - The distribution of aliphatic and aromatic hydrocarbons in surface sediments of the lower course of the Imo River (Nigeria) was investigated to determine the sources and fate of these compounds. The aliphatic fraction is characterized by a widespread contribution of highly weathered/biodegraded hydrocarbon residues (reflected in the absence of prominent n-alkane peaks coupled with the presence of 17alpha(H),21beta(H)-25-norhopane, an indicator of heavy hydrocarbon biodegradation) of Nigerian crude oils (confirmed by the occurrence of 18alpha(H) oleanane, a compound characteristic of oils of deltaic origin). The concentrations of polycyclic aromatic hydrocarbons (PAHs) ranging from 48 to 117 ng/g dry weight (dw; ?13PAHs) indicate a moderate pollution, possibly lowered by the sandy lithology and low organic carbon (OC) content of the sediments. Concentrations slightly decrease towards the estuary of the river, probably due to the fact that these stations are affected by tidal flushing of pollutants adsorbed on sediment particles and carried away by occasional storm to the Atlantic Ocean. A number of PAH ratios, including parent/alkylated and isomeric compounds, indicates a predominance of petrogenic sources, with a low contribution of pyrolytic inputs, particularly of fossil fuel combustion. On the basis of OC/ON (>10) and Per/SigmaPAHpenta- (>10) values, a diagenetic terrigenous OC was proposed as a source of perylene to the river. PMID- 26546421 TI - Spatial Variation in the Accumulation of Elements in Thalli of the Lichen Pseudevernia furfuracea (L.) Zopf Transplanted Around a Biomass Power Plant in Italy. AB - Thalli of the lichen Pseudevernia furfuracea were transplanted for 3 months at 32 sites located in and around an industrial area of S Italy whose main anthropogenic sources of atmospheric trace elements are a biomass power plant and vehicular emissions. Meteorological stations were deployed at four sites for finer detection of local wind patterns. The station near the biomass power plant showed a significant S-SE wind component not detectable by measurements made at the regional scale or by the other local meteorological stations. Sb, Sn, and Mo showed a very high degree of covariance and a statistically significant correlation with traffic rate. No element concentrations in the exposed thalli were correlated with distance from the biomass power plant, although Ti and Co concentrations showed a significant correlation with the "Potential Number of Times the Winds coming from the biomass power plant Reach each exposure Site" (PNTWRS). This value is calculated dividing the time (minutes) during the experimental trimester that the wind blows from the power plant into each of the four geographical sides by the time (minutes) the winds passing through the power plant take to reach the exposure sites in each of the four geographical sides.) during the period of thalli transplantation. Moreover, there were significant differences among clusters of sites with different levels of enrichment of Ti, Co, Al, V, and Cu and a "local control" group. These results, together with the high covariance of the Al-Ti and V-Co pairs, indicate an association between the biomass power plant and spatial variation of Ti, Co, Al, and V levels in the transplanted lichens. The nature of the fuels used in the biomass power plant explains the spatial variation of As, Cr, Cu, and Zn concentrations. PMID- 26546422 TI - Divergent Evolution of the repFII Replicon of IncF Plasmids Carrying Cytotoxic Necrotizing Factor cnf2, Cytolethal Distending Toxin cdtIII, and f17Ae Fimbrial Variant Genes in Type 2 Necrotoxigenic Escherichia coli Isolates from Calves. AB - Among the pathovars of Escherichia coli in cattle, necrotoxigenic E. coli (NTEC) is defined by the production of cytotoxic necrotizing factors (CNFs). In particular, type 2 NTEC (NTEC2) strains are frequent in diarrheic and septicemic calves and usually coproduce CNF type 2 (CNF2), cytolethal distending toxin type III (CDTIII), and fimbrial adhesins of the F17 family, whose genetic determinants have frequently been reported on the same Vir-like plasmid. In this study, we investigated the genetic environment of the cnf2, f17Ae, and cdtIII genes in a collection of fecal E. coli isolates recovered from 484 French and 58 Iranian calves. In particular, we highlighted the spread of cnf2, f17Ae, and cdtIII on similar 150-kb IncF plasmids harboring the newly assigned repFII replicon allele F74 in NTEC2 isolates. Interestingly, this 150-kb IncF plasmid differed from the 140-kb IncF plasmid harboring the newly assigned repFII replicon allele F75 and carrying cnf2 alone. These results suggest two divergent lineages of cnf2 carrying IncF plasmids depending on the presence of the f17Ae and cdtIII genes. This partition was observed in E. coli strains of unrelated backgrounds, suggesting two different evolutionary paths of cnf2-carrying IncF plasmids rather than divergent evolutions of NTEC2 clones. The driving forces for such divergent evolutions are not known, and further studies are required to clarify the selection of plasmid subtypes spreading virulence determinants in E. coli, in particular, plasmids of the IncF family. PMID- 26546423 TI - Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents. AB - Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis Menten kinetics with a Vmax of 465 U . mg(-1) for PPi hydrolysis (optimal at 42 degrees C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg(2+). Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by product generated in 2 M NaCl by UbaA (a "salt-loving" noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. PMID- 26546424 TI - Impact of Nisin-Activated Packaging on Microbiota of Beef Burgers during Storage. AB - Beef burgers were stored at 4 degrees C in a vacuum in nisin-activated antimicrobial packaging. Microbial ecology analyses were performed on samples collected between days 0 and 21 of storage to discover the population diversity. Two batches were analyzed using RNA-based denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. The active packaging retarded the growth of the total viable bacteria and lactic acid bacteria. Culture-independent analysis by pyrosequencing of RNA extracted directly from meat showed that Photobacterium phosphoreum, Lactococcus piscium, Lactobacillus sakei, and Leuconostoc carnosum were the major operational taxonomic units (OTUs) shared between control and treated samples. Beta diversity analysis of the 16S rRNA sequence data and RNA DGGE showed a clear separation between two batches based on the microbiota. Control samples from batch B showed a significant high abundance of some taxa sensitive to nisin, such as Kocuria rhizophila, Staphylococcus xylosus, Leuconostoc carnosum, and Carnobacterium divergens, compared to control samples from batch A. However, only from batch B was it possible to find a significant difference between controls and treated samples during storage due to the active packaging. Predicted metagenomes confirmed differences between the two batches and indicated that the use of nisin-based antimicrobial packaging can determine a reduction in the abundance of specific metabolic pathways related to spoilage. The present study aimed to assess the viable bacterial communities in beef burgers stored in nisin-based antimicrobial packaging, and it highlights the efficacy of this strategy to prolong beef burger shelf life. PMID- 26546425 TI - Terracidiphilus gabretensis gen. nov., sp. nov., an Abundant and Active Forest Soil Acidobacterium Important in Organic Matter Transformation. AB - Understanding the activity of bacteria in coniferous forests is highly important, due to the role of these environments as a global carbon sink. In a study of the microbial biodiversity of montane coniferous forest soil in the Bohemian Forest National Park (Czech Republic), we succeeded in isolating bacterial strain S55(T), which belongs to one of the most abundant operational taxonomic units (OTUs) in active bacterial populations, according to the analysis of RNA-derived 16S rRNA amplicons. The 16S rRNA gene sequence analysis showed that the species most closely related to strain S55(T) include Bryocella elongata SN10(T) (95.4% identity), Acidicapsa ligni WH120(T) (95.2% identity), and Telmatobacter bradus TPB6017(T) (95.0% identity), revealing that strain S55(T) should be classified within the phylum Acidobacteria, subdivision 1. Strain S55(T) is a rod-like bacterium that grows at acidic pH (3 to 6). Its phylogenetic, genotypic, phenotypic, and chemotaxonomic characteristics indicate that strain S55(T) corresponds to a new genus within the phylum Acidobacteria; thus, we propose the name Terracidiphilus gabretensis gen. nov., sp. nov. (strain S55(T) = NBRC 111238(T) = CECT 8791(T)). This strain produces extracellular enzymes implicated in the degradation of plant-derived biopolymers. Moreover, analysis of the genome sequence of strain S55(T) also reveals the presence of enzymatic machinery required for organic matter decomposition. Soil metatranscriptomic analyses found 132 genes from strain S55(T) being expressed in the forest soil, especially during winter. Our results suggest an important contribution of T. gabretensis S55(T) in the carbon cycle in the Picea abies coniferous forest. PMID- 26546426 TI - Hydrocarbon-Degrading Bacteria Exhibit a Species-Specific Response to Dispersed Oil while Moderating Ecotoxicity. AB - The Deepwater Horizon blowout in April 2010 represented the largest accidental marine oil spill and the largest release of chemical dispersants into the environment to date. While dispersant application may provide numerous benefits to oil spill response efforts, the impacts of dispersants and potential synergistic effects with crude oil on individual hydrocarbon-degrading bacteria are poorly understood. In this study, two environmentally relevant species of hydrocarbon-degrading bacteria were utilized to quantify the response to Macondo crude oil and Corexit 9500A-dispersed oil in terms of bacterial growth and oil degradation potential. In addition, specific hydrocarbon compounds were quantified in the dissolved phase of the medium and linked to ecotoxicity using a U.S. Environmental Protection Agency (EPA)-approved rotifer assay. Bacterial treatment significantly and drastically reduced the toxicity associated with dispersed oil (increasing the 50% lethal concentration [LC50] by 215%). The growth and crude oil degradation potential of Acinetobacter were inhibited by Corexit by 34% and 40%, respectively; conversely, Corexit significantly enhanced the growth of Alcanivorax by 10% relative to that in undispersed oil. Furthermore, both bacterial strains were shown to grow with Corexit as the sole carbon and energy source. Hydrocarbon-degrading bacterial species demonstrate a unique response to dispersed oil compared to their response to crude oil, with potentially opposing effects on toxicity. While some species have the potential to enhance the toxicity of crude oil by producing biosurfactants, the same bacteria may reduce the toxicity associated with dispersed oil through degradation or sequestration. PMID- 26546427 TI - Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes. AB - The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multiple inhibitory compounds. Having screened over 248 Gb of DNA cloned from 16 diverse soil metagenomes, we describe gain-of-function tolerance against acid, alcohol, and aldehyde inhibitors derived from hemicellulose and lignin, demonstrating that uncultured soil microbial communities hold tremendous genetic potential to address the toxicity of pretreated lignocellulose. We recovered genes previously known to confer tolerance to lignocellulosic inhibitors as well as novel genes that confer tolerance via unknown functions. For instance, we implicated galactose metabolism in overcoming the toxicity of lignin monomers and identified a decarboxylase that confers tolerance to ferulic acid; this enzyme has been shown to catalyze the production of 4-vinyl guaiacol, a valuable precursor to vanillin production. These metagenomic tolerance genes can enable the flexible design of hardy microbial catalysts, customized to withstand inhibitors abundant in specific bioprocessing applications. PMID- 26546428 TI - Application of the Environmental Relative Moldiness Index in Finland. AB - The environmental relative moldiness index (ERMI) metric was previously developed to quantify mold contamination in U.S. homes. This study determined the applicability of the ERMI for quantifying mold and moisture damage in Finnish residences. Homes of the LUKAS2 birth cohort in Finland were visually inspected for moisture damage and mold, and vacuumed floor dust samples were collected. An ERMI analysis including 36 mold-specific quantitative PCR assays was performed on the dust samples (n = 144), and the ERMI metric was analyzed against inspection based observations of moisture damage and mold. Our results show that the ERMI was significantly associated with certain observations of visible mold in Finnish homes but not with moisture damage. Several mold species occurred more frequently and at higher levels in Finnish than in U.S. homes. Modification of the ERMI toward Finnish conditions, using a subsample of LUKAS2 homes with and without moisture damage, resulted in a simplified metric based on 10 mold species. The Finnish ERMI (FERMI) performed substantially better in quantifying moisture and mold damage in Finnish homes, showing significant associations with various observations of visible mold, strongest when the damage was located in the child's main living area, as well as with mold odor and moisture damage. As shown in Finland, the ERMI as such is not equally well usable in different climates and geographic regions but may be remodeled to account for local outdoor and indoor fungal conditions as well as for moisture damage characteristics in a given country. PMID- 26546429 TI - The Extracellular Wall-Bound beta-N-Acetylglucosaminidase from Lactobacillus casei Is Involved in the Metabolism of the Human Milk Oligosaccharide Lacto-N Triose. AB - Human milk oligosaccharides (HMOs) are considered to play a key role in establishing and maintaining the infant gut microbiota. Lacto-N-triose forms part of both type 1 and type 2 HMOs and also of the glycan moieties of glycoproteins. Upstream of the previously characterized gene cluster involved in lacto-N-biose and galacto-N-biose metabolism from Lactobacillus casei BL23, there are two genes, bnaG and manA, encoding a beta-N-acetylglucosaminidase precursor and a mannose-6-phosphate isomerase, respectively. In this work, we show that L. casei is able to grow in the presence of lacto-N-triose as a carbon source. Inactivation of bnaG abolished the growth of L. casei on this oligosaccharide, demonstrating that BnaG is involved in its metabolism. Interestingly, whole cells of a bnaG mutant were totally devoid of beta-N-acetylglucosaminidase activity, suggesting that BnaG is an extracellular wall-attached enzyme. In addition to hydrolyzing lacto-N-triose into N-acetylglucosamine and lactose, the purified BnaG enzyme also catalyzed the hydrolysis of 3'-N-acetylglucosaminyl-mannose and 3'-N-acetylgalactosaminyl-galactose. L. casei can be cultured in the presence of 3'-N-acetylglucosaminyl-mannose as a carbon source, but, curiously, the bnaG mutant strain was not impaired in its utilization. These results indicate that the assimilation of 3'-N-acetylglucosaminyl-mannose is independent of BnaG. Enzyme activity and growth analysis with a manA-knockout mutant showed that ManA is involved in the utilization of the mannose moiety of 3'-N-acetylglucosaminyl mannose. Here we describe the physiological role of a beta-N acetylglucosaminidase in lactobacilli, and it supports the metabolic adaptation of L. casei to the N-acetylglucosaminide-rich gut niche. PMID- 26546430 TI - Microbial Activation of Wooden Vats Used for Traditional Cheese Production and Evolution of Neoformed Biofilms. AB - Three Lactococcus lactis subsp. cremoris strains were used to develop ad hoc biofilms on the surfaces of virgin wooden vats used for cheese production. Two vats (TZ) were tested under controlled conditions (pilot plant), and two vats (TA) were tested under uncontrolled conditions (industrial plant). In each plant, one vat (TA1 and TZ1) was used for the control, traditional production of PDO Vastedda della Valle del Belice (Vastedda) cheese, and one (TA2 and TZ2) was used for experimental production performed after lactococcal biofilm activation and the daily addition of a natural whey starter culture (NWSC). Microbiological and scanning electron microscopy analyses showed differences in terms of microbial levels and composition of the neoformed biofilms. The levels of the microbial groups investigated during cheese production showed significant differences between the control trials and between the control and experimental trials, but the differences were not particularly marked between the TA2 and TZ2 productions, which showed the largest numbers of mesophilic lactic acid bacterium (LAB) cocci. LAB populations were characterized phenotypically and genotypically, and 44 dominant strains belonging to 10 species were identified. Direct comparison of the polymorphic profiles of the LAB collected during cheese making showed that the addition of the NWSC reduced their biodiversity. Sensory evaluation showed that the microbial activation of the wooden vats with the multistrain Lactococcus culture generated cheeses with sensory attributes comparable to those of commercial cheese. Thus, neoformed biofilms enable a reduction of microbial variability and stabilize the sensorial attributes of Vastedda cheese. PMID- 26546431 TI - A c-Myc/miR-17-5p feedback loop regulates metastasis and invasion of hepatocellular carcinoma. AB - The molecular mechanisms that control metastasis of hepatocellular cancer (HCC) are still poorly understood. It has been determined that microRNA (miRNA) expression has tissue and cell specific, and decreased expression of specific miRNA could induce tumor genesis or metastasis. In this study, we identified that miR-17-5p was expressed lower in high metastatic capability HCC cell lines HCCLM3 and MHCC97H than low metastatic HCC cell line HepG2 by real-time (RT)-PCR. Restoration of miR-17-5p could significantly repress the invasiveness and metastasis of MHCC97H cell line. Furthermore, we validated c-Myc as a downstream and functional target of miR-17-5p using luciferase reporter assay. Immunohistochemical assay revealed that the expression of c-Myc protein levels was significantly increased in cancerous tissues compared with para-tumor tissues. After clinical data analysis, we observed that the higher level of c-Myc was significantly associated with a reduced overall survival (p = 0.0209). Consistent with previous research, we also demonstrated that c-Myc could upregulate the expression of miR-17-5p. Taken together, our data indicated that there is a regulatory feedback loop between miR-17-5p and c-Myc, in which miR-17 5p could suppress some of the distinguishing features, invasion, and metastasis, of oncogenic c-Myc in HCC cells, and meanwhile, miR-17-5p is upregulated by c-Myc role as a transcription factor, although further studies are still needed. PMID- 26546433 TI - PRSS1 mutations and the proteinase/antiproteinase imbalance in the pathogenesis of pancreatic cancer. AB - This study aimed to investigate the mutations in the serine protease 1 gene (PRSS1) and the imbalance between trypsin and alpha1-antitrypsin in patients with pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the sequences of PRSS1 from 65 patients with pancreatic cancer and 260 healthy controls, direct sequencing was performed, and the clinical features were analyzed. In addition, enzyme-linked immunosorbent assay (ELISA) was employed to detect serum trypsin and alpha1-antitrypsin in pancreatic cancer patients and healthy controls in the same period. Mutations were found at the promoter and exon 3 of the PRSS1 in patients with pancreatic cancer. That is, five patients had c.410 C > T mutation causing p.Thr 137 Met, and three patients had c. -338 T > G mutation at the promoter of the PRSS1. In patients with PRSS1 mutations, serum trypsin was 34.5 +/- 18.3 ng/mL, which was significantly higher than that in normal controls (10.65 +/- 6.03 ng/mL) and other pancreatic cancer (28.61 +/- 8.96 ng/mL). What is more, in pancreatic cancer patients, serum alpha1 antitrypsin was 1.69 +/- 0.86 g/L, which was comparable to that in normal controls (1.55 +/- 0.53 g/L), while the ratio of serum trypsin to alpha1 antitrypsin was 1.46-fold to normal controls. The results presented here have provided a greater insight into the PRSS1 mutations and proteinase-inhibitor interactions occurring in pancreatic cancer. PMID- 26546432 TI - Enhanced SLC34A2 in breast cancer stem cell-like cells induces chemotherapeutic resistance to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling. AB - Even though early detection methods and treatment options are greatly improved, chemoresistance is still a tremendous challenge for breast cancer therapy. Breast cancer stem cells (BCSCs) represent a subpopulation that is central to chemoresistance. We aim to investigate the relationship between SLC34A2 and chemoresistance in BCSCs and identify the underlying mechanisms by which SLC34A2 regulates chemoresistance in BCSCs. Fluorescence Activated Cell Sorting (FACS) analysis showed the presence of a variable fraction of CD44(+)CD24(-) cells in 25 out of 25 breast cancer samples. We cultured primary breast cancer sample cells and breast cancer cell line cells to induce sphere formation in serum-free medium. Following sorting of CD44(+)CD24(-) cells from spheres, we showed that CD44(+)CD24(-) cells displayed stem cell-like features and were resistant to chemotherapy drug doxorubicin. Significantly, enhanced SLC34A2 expression correlated with chemoresponse and survival of breast cancer patients. We subsequently indicated that increased SLC34A2 expression in BCSCs directly contributed to their chemoresistance by a series of in vitro and in vivo experiments. Furthermore, we demonstrated that SLC34A2 induced chemoresistance in BCSCs via SLC34A2-Bmi1-ABCC5 signaling. Finally, we showed that ABCC5 was a direct transcriptional target of Bmi1 by chromatin immunoprecipitation (ChIP). In conclusion, our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer. PMID- 26546434 TI - DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer. AB - Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer. PMID- 26546435 TI - CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors. AB - Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4's function and mechanisms. Co immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1-11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability , clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and beta-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors. PMID- 26546436 TI - miR-122 inhibits cancer cell malignancy by targeting PKM2 in gallbladder carcinoma. AB - Gallbladder cancer (GBC) is one of the lethal diseases of digestive system. Increasing evidence prompt that microRNAs (miRs) might provide a novel therapeutical target for malignant disease. The antitumor effect of miR-122 to GBC is worth to be investigated. miR-122 expression level in GBC tissue sample and cell lines were assayed by qRT-PCR. miR-122 mimics were transfected for upregulation of miR-122 expression. Cell function was assayed by CCK8, flow cytometry, wound healing assay, migration assay, and invasion assay. The target genes of miR-122 were predicated by TargetScan online program and verified by western blot and luciferase report gene assay. miR-122 was decreased in GBC tissue and cell lines. The exogenous introduction of miR-122 exhibits multiple antitumor effect in GBC cell proliferation, invasion, and metastasis. Further studies revealed that the PKM2 was a regulative target of miR-122 in GBC cell. miR-122 also inhibits TGF-beta-induced epithelium mesenchymal transformation of GBC cell by downregulating PKM2 expression. These findings suggest that miR-122 plays an important role in tumorigenesis of GBC through interfering PKM2, highlighting its usefulness as a potential therapeutic agent in GBC. PMID- 26546437 TI - Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma. AB - Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues (P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients. PMID- 26546438 TI - RRAD inhibits aerobic glycolysis, invasion, and migration and is associated with poor prognosis in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancer worldwide. However, the mechanism underlying the HCC development remains unclear. Ras-related associated with diabetes (RRAD) is a small Ras-related GTPase which has been implicated in metabolic disease and several types of cancer, yet its functions in HCC remain unknown. A tissue microarray constructed by 90 paired HCC tissues and adjacent non-cancerous liver tissues was used to examine the protein levels of RRAD, and the messenger RNA (mRNA) expression of RRAD was also detected in a subset of this cohort. The prognostic significance of RRAD was estimated by the Kaplan-Meier analysis and Cox regression. The glucose utilization assay and lactate production assay were performed to measure the role of RRAD in HCC glycolysis. The effect of RRAD in HCC invasion and metastasis was analyzed by transwell assays. Our results suggested that the expression of RRAD was downregulated in HCC tissues compared to the adjacent non-tumorous liver tissues both in mRNA and protein levels and lower RRAD expression served as an independent prognostic indicator for the survival of HCC patients. Moreover, RRAD inhibited hepatoma cell aerobic glycolysis by negatively regulating the expression of glucose transporter 1 (GLUT1) and hexokinase II (HK-II). In addition, RRAD inhibition dramatically increased hepatoma cell invasion and metastasis. In conclusion, our study revealed that RRAD expression was decreased in HCC tumor tissues and predicted poor clinical outcome for HCC patients and played an important role in regulating aerobic glycolysis and cell invasion and metastasis and may represent potential targets for improving the treatment of HCC. PMID- 26546439 TI - Filamin A (FLNA) modulates chemosensitivity to docetaxel in triple-negative breast cancer through the MAPK/ERK pathway. AB - A previous RNA interference (RNAi) screen identified filamin A (FLNA) as a potential biomarker to predict chemosensitivity in triple-negative breast cancer (TNBC). However, its ability to modulate chemosensitivity and the underlying mechanism has not been investigated. Genetic manipulation of FLNA expression has been performed in an immortalized noncancerous human mammary epithelial cell line and four TNBC cell lines to investigate its effect on chemosensitivity. Western blot analysis was performed to identify the potential signaling pathway involved. Xenograft mouse model was used to examine the in vivo role of FLNA in modulating chemosensitivity. Overexpression of FLNA conferred chemoresistance to docetaxel in noncancerous human mammary epithelial cells. Knockdown of FLNA sensitized four TNBC cell lines, MDA-MB-231, HCC38, Htb126, and HCC1937 to docetaxel which was reversed by reconstituted FLNA expression. Decreased FLNA expression correlated with decreased activation of ERK. Constitutive activation of ERK2 reversed siFLNA induced chemosensitization. Inhibition of MEK1 recapitulates the effect of FLNA knockdown. MDA-MB-231 xenograft with FLNA knockdown showed enhanced response to docetaxel compared with control xenograft with increased apoptosis. FLNA can function as a modulator of chemosensitivity to docetaxel in TNBC cells through regulation of the MAPK/ERK pathway both in vitro and in vivo. FLNA may serve as a novel therapeutic target for improvement of chemotherapy efficacy in TNBC. PMID- 26546440 TI - The pig as preclinical model for laparoscopic vagus nerve stimulation. AB - PURPOSE: Cervical vagus nerve stimulation (VNS) prevents manipulation-induced intestinal inflammation and improves intestinal transit in a mouse model of postoperative ileus (POI). Cervical VNS, however, is accompanied by cardiovascular and respiratory side effects. In view of potential clinical application, we therefore evaluated the safety and feasibility of abdominal VNS via laparoscopic approach in a porcine model. METHODS: Six pigs were used in a non-survival study for both cervical and abdominal VNS. Two cardiac pacing electrodes were positioned around the right cervical and posterior abdominal vagus nerve and connected to an external stimulator. VNS was performed using four different settings (5 and 20 Hz, 0.5 and 1 ms pulse width) during 2 min with ECG recording. Laparoscopic VNS was timed and videotaped, and technical difficulties were noted. A validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire was used to evaluate the task and workload. RESULTS: The procedure was completed in all pigs with 4-port laparoscopic technique. Cervical and abdominal VNS were performed after correct identification and isolation of the nerve, and positioning of the electrodes around the nerve. Median laparoscopic operating time was 16 min (range 8-33 min), and median NASA TLX was 31 (range 11-74). No major complications were encountered. Reduction of heart rate was between 5.5 and 14% for cervical VNS and undetectable for abdominal VNS. CONCLUSION: In a porcine model, laparoscopic VNS is feasible and safe with cardiac pacing electrodes and may lead to a similar novel approach in humans in the near future. PMID- 26546441 TI - Isolated colorectal metastasis to the stomach 10 years after primary resection. PMID- 26546442 TI - Letter to the Editor on the article "Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta-analysis of 1071 patients". PMID- 26546443 TI - Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread. AB - PURPOSE: Although lymph node metastases to pancreatic and gastroepiploic lymph node stations in transverse colon cancer have been described, the mode of lymphatic spread in this area remains unclear. This study was undertaken to describe possible pathways of aberrant lymphatic spread in the complex anatomic area of the proximal superior mesenteric artery and vein, the greater omentum, and the lower pancreatic border. METHODS: Abdominal specimens obtained from four cadaveric donors were dissected according to the principles of complete mesocolic excision. The vascular architecture of the transverse colon was scrutinized in search of possible pathways of lymphatic spread to the pancreatic and gastroepiploic lymph nodes. RESULTS: Vascular connections between the transverse colon and the greater omentum at the level of both the hepatic and the splenic flexures could be identified. In addition, small vessels running from the transverse mesocolon to the lower pancreatic border in the area between the middle colic artery and the inferior mesenteric vein were demonstrated. Moreover, venous tributaries to the gastrocolic trunk could be exposed to highlight its surgical importance as a guiding structure for complete mesocolic excision. CONCLUSION: The technical feasibility to clearly separate embryologic compartments by predefined tissue planes in complete mesocolic excision was confirmed. However, the vicinity of all three endodermal intestinal segments (foregut, midgut, and hindgut) obviously gives way to vascular connections that might serve as potential pathways for lymphatic metastatic spread of transverse colon cancer. PMID- 26546444 TI - Photosynthesis in estuarine intertidal microphytobenthos is limited by inorganic carbon availability. AB - The effects of dissolved inorganic carbon (DIC) availability on photosynthesis were studied in two estuarine intertidal microphytobenthos (MPB) communities and in the model diatom species Phaeodactylum tricornutum. Kinetics of DIC acquisition, measured with a liquid-phase oxygen electrode, showed higher K(1/2)(DIC) (0.31 mM) and Vm (7.78 nmol min(-1) ug (Chl a)(-1)) for MPB suspensions than for P. tricornutum (K(1/2)(DIC) = 0.23 mM; Vm = 4.64 nmol min( 1) ug (Chl a)(-1)), suggesting the predominance of species with lower affinity for DIC and higher photosynthetic capacity in the MPB. The net photosynthetic rate of the MPB suspensions reached saturation at a DIC concentration of 1-1.5 mM. This range was lower than the concentrations found in the interstitial water of the top 5-mm sediment layer, suggesting no limitation of photosynthesis by DIC in the MPB communities. Accordingly, carbon isotope discrimination revealed a moderate activity of CO2-concentrating mechanisms in the MPB. However, addition of NaHCO3 to intact MPB biofilms caused a significant increase in the relative maximum photosynthetic electron transport rate (rETR max) measured by imaging pulse-amplitude modulated chlorophyll a fluorescence. These results suggest local depletion of DIC at the photic layer of the sediment (the first few hundred um), where MPB cells accumulate during diurnal low tides. This work provides the first direct experimental evidence of DIC limitation of photosynthesis in highly productive intertidal MPB communities. PMID- 26546445 TI - Functional Conservation in the SIAMESE-RELATED Family of Cyclin-Dependent Kinase Inhibitors in Land Plants. AB - The best-characterized members of the plant-specific SIAMESE-RELATED (SMR) family of cyclin-dependent kinase inhibitors regulate the transition from the mitotic cell cycle to endoreplication, also known as endoreduplication, an altered version of the cell cycle in which DNA is replicated without cell division. Some other family members are implicated in cell cycle responses to biotic and abiotic stresses. However, the functions of most SMRs remain unknown, and the specific cyclin-dependent kinase complexes inhibited by SMRs are unclear. Here, we demonstrate that a diverse group of SMRs, including an SMR from the bryophyte Physcomitrella patens, can complement an Arabidopsis thaliana siamese (sim) mutant and that both Arabidopsis SIM and P. patens SMR can inhibit CDK activity in vitro. Furthermore, we show that Arabidopsis SIM can bind to and inhibit both CDKA;1 and CDKB1;1. Finally, we show that SMR2 acts to restrict cell proliferation during leaf growth in Arabidopsis and that SIM, SMR1/LGO, and SMR2 play overlapping roles in controlling the transition from cell division to endoreplication during leaf development. These results indicate that differences in SMR function in plant growth and development are primarily due to differences in transcriptional and posttranscriptional regulation, rather than to differences in fundamental biochemical function. PMID- 26546446 TI - Strigolactone Signaling in Arabidopsis Regulates Shoot Development by Targeting D53-Like SMXL Repressor Proteins for Ubiquitination and Degradation. AB - Strigolactones (SLs) are carotenoid-derived phytohormones that control many aspects of plant development, including shoot branching, leaf shape, stem secondary thickening, and lateral root growth. In rice (Oryza sativa), SL signaling requires the degradation of DWARF53 (D53), mediated by a complex including D14 and D3, but in Arabidopsis thaliana, the components and mechanism of SL signaling involving the D3 ortholog MORE AXILLARY GROWTH2 (MAX2) are unknown. Here, we show that SL-dependent regulation of shoot branching in Arabidopsis requires three D53-like proteins, SUPPRESSOR OF MORE AXILLARY GROWTH2 LIKE6 (SMXL6), SMXL7, and SMXL8. The smxl6 smxl7 smxl8 triple mutant suppresses the highly branched phenotypes of max2 and the SL-deficient mutant max3. Overexpression of a mutant form of SMXL6 that is resistant to SL-induced ubiquitination and degradation enhances shoot branching. Exogenous application of the SL analog rac-GR24 causes ubiquitination and degradation of SMXL6, 7, and 8; this requires D14 and MAX2. D53-like SMXLs form complexes with MAX2 and TOPLESS RELATED PROTEIN2 (TPR2) and interact with D14 in a GR24-responsive manner. Furthermore, D53-like SMXLs exhibit TPR2-dependent transcriptional repression activity and repress the expression of BRANCHED1. Our findings reveal that in Arabidopsis, D53-like SMXLs act with TPR2 to repress transcription and so allow lateral bud outgrowth but that SL-induced degradation of D53-like proteins activates transcription to inhibit outgrowth. PMID- 26546447 TI - SMAX1-LIKE/D53 Family Members Enable Distinct MAX2-Dependent Responses to Strigolactones and Karrikins in Arabidopsis. AB - The plant hormones strigolactones and smoke-derived karrikins are butenolide signals that control distinct aspects of plant development. Perception of both molecules in Arabidopsis thaliana requires the F-box protein MORE AXILLARY GROWTH2 (MAX2). Recent studies suggest that the homologous SUPPRESSOR OF MAX2 1 (SMAX1) in Arabidopsis and DWARF53 (D53) in rice (Oryza sativa) are downstream targets of MAX2. Through an extensive analysis of loss-of-function mutants, we demonstrate that the Arabidopsis SMAX1-LIKE genes SMXL6, SMXL7, and SMXL8 are co orthologs of rice D53 that promote shoot branching. SMXL7 is degraded rapidly after treatment with the synthetic strigolactone mixture rac-GR24. Like D53, SMXL7 degradation is MAX2- and D14-dependent and can be prevented by deletion of a putative P-loop. Loss of SMXL6,7,8 suppresses several other strigolactone related phenotypes in max2, including increased auxin transport and PIN1 accumulation, and increased lateral root density. Although only SMAX1 regulates germination and hypocotyl elongation, SMAX1 and SMXL6,7,8 have complementary roles in the control of leaf morphology. Our data indicate that SMAX1 and SMXL6,7,8 repress karrikin and strigolactone signaling, respectively, and suggest that all MAX2-dependent growth effects are mediated by degradation of SMAX1/SMXL proteins. We propose that functional diversification within the SMXL family enabled responses to different butenolide signals through a shared regulatory mechanism. PMID- 26546448 TI - Circular RNAs in monkey muscle: age-dependent changes. AB - Circular RNAs (circRNAs) have been identified in numerous species, including human, mouse, nematode, and coelacanth. They are believed to function as regulators of gene expression at least in part by sponging microRNAs. Here, we describe the identification of circRNAs in monkey (Rhesus macaque) skeletal muscle. RNA sequencing analysis was employed to identify and annotate ~12,000 circRNAs, including numerous circular intronic RNAs (ciRNAs), from skeletal muscle of monkeys of a range of ages. Reverse transcription followed by real-time quantitative (q)PCR analysis verified the presence of these circRNAs, including the existence of several highly abundant circRNAs, and the differential abundance of a subset of circRNAs as a function of age. Taken together, our study has documented systematically circRNAs expressed in skeletal muscle and has identified circRNAs differentially abundant with advancing muscle age. We propose that some of these circRNAs might influence muscle function. PMID- 26546449 TI - Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40 % of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors. METHODS: To dissect the relative contributions of the central nervous system from those of the hematopoietic compartment, we generated bone marrow chimeras between healthy control (MRL/+) and lupus-prone MRL/Tnfrsf6 (lpr/lpr) mice (MRL/+ -> MRL/lpr), as well as control chimeras. After bone marrow reconstitution, mice underwent extensive behavioral testing, analysis of brain tissue, and histological assessment. RESULTS: Despite transfer of healthy MRL/+ bone marrow and marked attenuation of systemic disease, we found that MRL/+ -> MRL/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits, comparable to MRL/lpr -> MRL/lpr control transplanted mice and the behavioral profile previously established in MRL/lpr mice. Moreover, MRL/+ -> MRL/lpr chimeric mice displayed increased brain RANTES expression, neurodegeneration, and cellular infiltration in the choroid plexus, as well as blood brain barrier disruption, all in the absence of significant systemic autoimmunity. CONCLUSIONS: Chimeric MRL/+ -> MRL/lpr mice displayed no attenuation of the behavioral phenotype found in MRL/lpr mice, despite normalized serum autoantibodies and conserved renal function. Therefore, neuropsychiatric disease in the MRL/lpr lupus-prone strain of mice can occur absent any major contributions from systemic autoimmunity. PMID- 26546450 TI - Antioxidant potential, in vitro cytotoxicity and apoptotic effect induced by crude organic extract of Anthracophyllum lateritium against RD sarcoma cells. AB - BACKGROUND: Macrofungi have an established history of use in traditional oriental medicine. Anthracophyllum lateritium is a terrestrial macrofungus found in the dry zone forest reserves in Sri Lanka. Yet there are no scientific reports on bioactive properties of this species. Hence, the current study was aimed at determining the antioxidant potential, in vitro antiproliferative activity and apoptotic effect induced by crude methanolic extract of A. lateritium against RD sarcoma cell line. METHOD: The crude extract of A. lateritium was dissolved in methanol (MEFCA) and antioxidant activity was evaluated using in vitro assays: inhibition of DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging, ferric ion reducing power and 2-deoxy-D-ribose degradation assay. Total phenol and flavonoid contents of MEFCA were assayed using folin Ciocalteu method and aluminium chloride colorimetric method. In vitro cytotoxicity was determined using MTT assay against RD cells after 24 h exposure to MEFCA. Ethidium bromide/ acridine orange staining, DNA fragmentation and protein synthesis experiments were used to study the apoptotic features and antiproliferative activities of the treated cells. Glutathione assay and griess nitrite assay were used to analyze the reduced glutathione content and liberation of nitric oxide from apoptotic cells. RESULTS: MEFCA showed promising antioxidant activity with EC50 values of 8.00 +/- 0.35 MUg/mL for DPPH scavenging and 83.33 +/- 0.45 MUg/mL for 2-deoxy-D-ribose degradation assay. The phenolic content was 265.15 +/- 0.46 of (w/w) % of Gallic acid equivalents and flavonoid content was 173.01 +/- 0.35 of (w/w) % of Epigallocatechingallate. A. lateritium showed strong in vitro cytotoxic activity with an EC50 of 18.80 +/- 4.83 MUg/mL for MTT assay against RD cells. Ethidium bromide/acridine orange staining and DNA fragmentation indicated the apoptotic features of treated cells. Protein levels showed a dose dependent decrease supporting the fact that A. lateritium induces apoptosis of treated cells. Glutathione content and nitric oxide content of cells exhibited a dose dependent increase suggesting the apoptosis of RD cells was mediated by both nitrie ions and nitric oxide. CONCLUSIONS: The crude extract of the A. lateritium exhibited potent antioxidant, antiproliferative activity and apoptotic effect against RD cells providing supportive evidence for the ethnopharmacological use of this fungus in control of oxidative damage and remedy of cancer. PMID- 26546451 TI - Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer. AB - We previously observed T-bet(+) lymphocytes to be associated with a good prognosis in a cohort of women with familial breast cancer. To validate this finding, we evaluated lymphocyte T-bet expression in an independent unselected prospectively accrued series of women with lymph node-negative breast carcinoma. T-bet and clinicopathologic data were available for 614 women. Hormone receptors, HER2, Ki-67, CK5, EGFR, p53, and T-bet status were determined using IHC and/or biochemical methods. Tumors were assigned to luminal A, luminal B, HER2, and basal subtypes based on the expression of IHC markers. Multiple cutpoints were examined in a univariate penalized Cox model to stratify tumors into T bet(+/high) and T-bet(-/low). Fisher exact test was used to analyze T-bet associations with clinicopathologic variables, IHC markers, and molecular subtype. Survival analyses were by the Cox proportional hazards model. All tests were two sided. A test with a P value < 0.05 was considered statistically significant. T-bet(+/high) tumor status was significantly associated with large tumor size, high grade, hormone receptor negativity, CK5, EGFR and p53 positivity, high Ki-67, and basal subtype. With a median follow-up of 96.5 months, T-bet(-/low) tumor status was associated with a reduced disease-free survival compared with T-bet(+/high) tumor status in multivariate analysis (P = 0.0027; relative risk = 5.62; 95% confidence intervals, 1.48-50.19). Despite being associated with adverse clinicopathologic characteristics, T-bet(+) tumor infiltrating lymphoid cells are associated with a favorable outcome. This supports their role in Th1-mediated antitumor activity and may provide insight for the development of new therapeutic strategies. PMID- 26546452 TI - PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells. AB - Blocking the programmed death-1 (PD-1) pathway has clinical benefit in metastatic cancer and has led to the approval of the mAbs pembrolizumab and nivolumab to treat melanoma and nivolumab for non-small cell lung cancer. Expression of PD-L1 on the cell surface of either tumor cells or infiltrating immune cells is associated with a higher likelihood of response to PD-1 blockade in multiple studies. Most mAbs to PD-L1 in use are directed to its extracellular domain and immunohistochemically stain tumor tissue with a mixture of cytoplasmic and membrane staining. Cytoplasmic staining obscures the interpretation of a positive reaction on the tumor cell membrane, and thus affects the accuracy of PD-L1 scoring systems. We developed a mAb to the cytoplasmic domain of PD-L1, 405.9A11 (9A11), which is both more selective for membranous PD-L1 and more sensitive in IHC and Western blotting, compared with previous mAbs specific for the PD-L1 extracellular domain. Here, we compare immunohistochemical staining patterns of PD-L1 expression in five types of tumors, using five PD-L1 mAbs: 9A11, 7G11, and three commercially available mAbs. We demonstrate that 9A11, as well as two other cytoplasmic domain-specific mAbs, E1L3N and SP142, can clearly delineate the membrane of PD-L1-positive cells in formalin-fixed paraffin-embedded tissue and facilitate interpretation of staining results. PMID- 26546453 TI - Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model. AB - Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma. PMID- 26546454 TI - Transcriptomic analysis of cobalt stress in the marine yeast Debaryomyces hansenii. AB - The yeast Debaryomyces hansenii overproduces riboflavin upon exposure to subtoxic levels of cobalt (Co(+2)). However, mechanisms for survival have yet to be studied and have been hindered by D. hansenii's high genetic heterogeneity among strains. In this study, we used transcriptomic analyses and RNA-seq in order to identify differentially expressed genes in D. hansenii in response to cobalt exposure. Highly upregulated genes under this condition were identified to primarily comprise DNA damage and repair genes, oxidative stress response genes, and genes for cell wall integrity and growth. The main response of D. hansenii to heavy metal stress is the activation of non-enzymatic oxidative stress response mechanisms and control of biological production of reactive oxygen species. Our results indicate that D. hansenii does not seem to be pre-adapted to survive high concentrations of heavy metals. These organisms appear to possess genetic survival and detoxification mechanisms that enable the cells to recover from heavy metal stress. PMID- 26546455 TI - Proteomic analysis of hyperadhesive Candida glabrata clinical isolates reveals a core wall proteome and differential incorporation of adhesins. AB - Attachment to human host tissues or abiotic medical devices is a key step in the development of infections by Candida glabrata. The genome of this pathogenic yeast codes for a large number of adhesins, but proteomic work using reference strains has shown incorporation of only few adhesins in the cell wall. By making inventories of the wall proteomes of hyperadhesive clinical isolates and reference strain CBS138 using mass spectrometry, we describe the cell wall proteome of C. glabrata and tested the hypothesis that hyperadhesive isolates display differential incorporation of adhesins. Two clinical strains (PEU382 and PEU427) were selected, which both were hyperadhesive to polystyrene and showed high surface hydrophobicity. Cell wall proteome analysis under biofilm-forming conditions identified a core proteome of about 20 proteins present in all C. glabrata strains. In addition, 12 adhesin-like wall proteins were identified in the hyperadherent strains, including six novel adhesins (Awp8-13) of which only Awp12 was also present in CBS138. We conclude that the hyperadhesive capacity of these two clinical C. glabrata isolates is correlated with increased and differential incorporation of cell wall adhesins. Future studies should elucidate the role of the identified proteins in the establishment of C. glabrata infections. PMID- 26546456 TI - Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer. AB - PURPOSE: Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR). METHODS: A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non sarcopenia/high NLR, and non-sarcopenia/low NLR. RESULTS: Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p < 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p < 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001). CONCLUSIONS: In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients. PMID- 26546457 TI - Efficacy of venlafaxine for the relief of taxane and oxaliplatin-induced acute neurotoxicity: a single-center retrospective case-control study. AB - BACKGROUND: Oxaliplatin and taxane-induced neurosensory toxicity is dose-limiting and mostly presents with acute symptoms that affect the activities of daily living and overall quality of life. The objective of the present study is to assess the relief of acute neuropathy with venlafaxine treatment during the chemotherapy period. PATIENTS AND METHODS: In this retrospective case-control study, from January 2010 to February 2015, patients who experienced treatment with oxaliplatin and taxane-induced acute neurotoxicity were evaluated according to the NCI-CTCAE v. 4.03 grading scale. Neurotoxicity was evaluated using a numeric rating scale (NRS) for pain intensity and experienced relief under the treatment of venlafaxine and using a neuropathic pain symptom inventory scale (NPSI) for the style of complaints. Patients who were diagnosed as mildly depressed according to the HOST anxiety and depression scale and who had grade 1 to 3 sensory neurotoxicity based on the NCI-CTCAE v. 4.03 grading scale, and who also reported >= 4/10 on a NRS were eligible. The primary end point was the rate of more than 75 % symptomatic relief under venlafaxine treatment. RESULTS: Two hundred six patients were included (82 % female, median age: 52.7 years). Most patients had breast, gynecologic, and colon cancer (93.4 %). Ninety-one patients who received venlafaxine and 115 patients as the control group were assessed for neurotoxicity every 3 weeks. Based on the NRS, a rate of more than 75 % symptomatic relief was 53.5, 58.3, and 45.2 % in venlafaxine arm versus 0, 0, and 0 % in the control arm in the first, second, and third visits, respectively. Side effects of venlafaxine (n = 7) were grade 1-2 nausea/vomiting (3.2 %) and asthenia/somnolence (3.2 %) without grade 3-4 events. CONCLUSION: Venlafaxine has a significant clinical activity against taxane-oxaliplatin-induced acute neurosensory toxicity. PMID- 26546458 TI - The current status of malaria epidemiology in Bolifamba, atypical Cameroonian rainforest zone: an assessment of intervention strategies and seasonal variations. AB - BACKGROUND: Global malaria has been on the decline over the past decade due to expansion of interventions. The present study aimed at determining the current status of malaria epidemiology in the context of sustained interventions and seasonal variations in Bolifamba, which represents a typical semi-urban malaria endemic community in the Cameroonian rainforest. METHODS: A monthly cross sectional survey was carried out in Bolifamba, a multi ethnic semi-urban locality on the eastern flanks of Mt Cameroon, for a year during which blood samples were collected from participants and examined for malaria parasites by microscopy. Correlation analysis of seasonal/monthly malaria prevalence was done with weather data from Ekona, a nearby village with a meteorological station. Intervention strategy such as use of Insecticide Treated Bed Net (ITBN) and risk factors such as duration of stay in the locality, age and housing type were also investigated. RESULTS: The results revealed a malaria prevalence of 38.3 % in the rainy season, which was significantly higher than 24.4 % observed in the dry season (P < 0.0001). A high prevalence of asymptomatic malaria which was more than double the prevalence of symptomatic malaria on a monthly basis was observed, 30.7 % vs 17.8 % in the rainy and dry season respectively (p < 0.0001) and asymptomatic malaria was significantly associated with anemia (p < 0.005). April was the peak month of malaria prevalence and coincided with peak periods of both asymptomatic and symptomatic malaria. The Plasmodium falciparum parasite rates in the 2- up to 10 years age group (PfPR(2-10)) was 40.8 %. The regular use of ITBN was significantly associated with low prevalence of 31.7 % as opposed to irregular or non-usage of ITBN 38.2 % (p < 0.05). Log of parasite load was found to initially increase to 2.49 with less than 5 years of stay, and decreased gradually with increasing duration of stay in the locality (p = 0.046). Climatic factors were significantly and positively associated with monthly malaria prevalence and the strongest predictors of malaria prevalence were rainfall and minimum temperature with r values of 0.563 and 0.6 respectively. CONCLUSIONS: The study highlights the role of seasonal change in modifying malaria prevalence during the year and the beneficial effect of ITBN. It also underscores a sublime problem of asymptomatic malaria associated with anemia, and indicates that partial immunity is acquired with prolonged stay in Bolifamba. This preliminary result is the basis of ongoing work to identify the antigens involved in acquired immunity. PMID- 26546459 TI - Production of grooming-associated sounds by chimpanzees (Pan troglodytes) at Ngogo: variation, social learning, and possible functions. AB - Chimpanzees (Pan troglodytes) use some communicative signals flexibly and voluntarily, with use influenced by learning. These signals include some vocalizations and also sounds made using the lips, oral cavity, and/or teeth, but not the vocal tract, such as "attention-getting" sounds directed at humans by captive chimpanzees and lip smacking during social grooming. Chimpanzees at Ngogo, in Kibale National Park, Uganda, make four distinct sounds while grooming others. Here, I present data on two of these ("splutters" and "teeth chomps") and consider whether social learning contributes to variation in their production and whether they serve social functions. Higher congruence in the use of these two sounds between dyads of maternal relatives than dyads of non-relatives implies that social learning occurs and mostly involves vertical transmission, but the results are not conclusive and it is unclear which learning mechanisms may be involved. In grooming between adult males, tooth chomps and splutters were more likely in long than in short bouts; in bouts that were bidirectional rather than unidirectional; in grooming directed toward high-ranking males than toward low ranking males; and in bouts between allies than in those between non-allies. Males were also more likely to make these sounds while they were grooming other males than while they were grooming females. These results are expected if the sounds promote social bonds and induce tolerance of proximity and of grooming by high-ranking males. However, the alternative hypothesis that the sounds are merely associated with motivation to groom, with no additional social function, cannot be ruled out. Limited data showing that bouts accompanied by teeth chomping or spluttering at their initiation were longer than bouts for which this was not the case point toward a social function, but more data are needed for a definitive test. Comparison to other research sites shows that the possible existence of grooming-specific sound dialects in chimpanzees deserves further investigation. PMID- 26546460 TI - Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression. AB - PURPOSE: Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells. METHODS: Cell viability was determined by MTT assay after evodiamine treatment. Wound-healing assay and Boyden transwell system were used to evaluate the inhibitory effects of evodiamine on cell migration and invasion. MMP-2/9 activity was determined using commercial detection kits. The levels of associated proteins involved in the regulation of cell migration and invasion were analyzed by Western blotting. RESULTS: Evodiamine effectively inhibited the migration and invasion of HONE1 and CNE1 cells, and hardly affected cell proliferation, but significantly suppressed cell adhesion activity in vitro. Additionally, evodiamine treatment significantly decreased mRNA and protein levels of MMP-2 and its activity in the NPC cells, but had little effects on MMP-9 mRNA and protein levels and its activity. Further investigation revealed that evodiamine inhibited the translocation of NF-kappaB p65, which involves the regulation of MMP-2 expression in cancer invasion. Additionally, evodiamine treatment did not significantly affect the protein levels of JNK, p38, Akt, and their phosphorylated forms and ERK1/2, but strongly attenuated ERK1/2 phosphorylation level, which at least partly accounts for the signal pathway of evodiamine inhibited migration and invasion of NPC cells. CONCLUSION: These findings demonstrate that evodiamine inhibits the migration and invasiveness of NPC cells, and it is probably a potential agent for the treatment of NPC invasion and metastasis. PMID- 26546461 TI - A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients. AB - PURPOSE: Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and pharmacogenetic screening is warranted for better management of imatinib therapy. The present study was framed to explore the influence of common drug transporter gene polymorphisms of ABCB1, ABCG2, OCT1 and trough level concentration on commonly occurring adverse events in CML patients treated with imatinib mesylate. METHODS: A total number of 111 patients in chronic phase (Philadelphia chromosome +ve) were included in the study. The plasma drug concentration of imatinib was estimated using LC-MS/MS method. RESULTS: The mean +/- SD trough level concentration of imatinib mesylate was found to be 1430.7 +/- 438.7 ng/ml. The trough level concentration at steady state (Cmin.ss) was significantly higher in patients with grade 2-4 thrombocytopenia compared with patients without the adverse event (P value 0.033). CONCLUSION: The drug level of imatinib in plasma correlates with the severity of thrombocytopenia, which adds to the utility of TDM in the management of CML patients. PMID- 26546462 TI - NR6A1 couples with cAMP response element binding protein and regulates vascular smooth muscle cell migration. AB - Vascular smooth muscle cell (VSMC) migration is implicated in atherosclerosis and restenosis. Nuclear receptor subfamily 6, group A, member 1 (NR6A1) is involved in regulating embryonic stem cell differentiation, reproduction, neuronal differentiation. Functional cooperation between cAMP response element modulator tau (CREMtau) and NR6A1 can direct gene expression in cells. cAMP response element binding protein (CREB) plays a key role in VSMC migration. In this study, we sought to determine whether CREB involved in NR6A1-modulated VSMC migration. VSMCs treated with platelet-derived growth factor-BB (PDGF-BB) displayed reduced mRNA and protein levels of NR6A1. Adenovirus-mediated expression of NR6A1 (Ad NR6A1) could inhibit PDGF-BB- and serum-induced VSMC migration. The mRNA and protein expressions of secreted phosphoprotein 1 (SPP1) were down-regulated by NR6A1 overexpression. SPP1 promoter reporter activity was repressed by NR6A1. NR6A1 was found to physically couple with nuclear actin and the large subunit of RNA polymerase II. Furthermore, we showed that CREB interacted with NR6A1 in VSMCs. NR6A1 overexpression repressed cAMP response element (CRE) activity. ChIP assay revealed that NR6A1 bind to SPP1 promoter. Luciferase reporter assay showed that NR6A1 regulated SPP1 promoter activity via a putative CRE site. Adenovirus mediated local NR6A1 gene transfer attenuated stenosis after balloon-induced arterial injury in Sprague-Dawley rats. Taken together, this study provided experimental evidence that NR6A1 modulated SPP1 expression via its binding with CREB protein in VSMCs. We also revealed a NR6A1-CREB-SPP1 axis that serves as a regulatory mechanism for atherosclerosis and restenosis. PMID- 26546463 TI - Ubiquitin conjugating enzyme E2-N and sequestosome-1 (p62) are components of the ubiquitination process mediated by the malin-laforin E3-ubiquitin ligase complex. AB - Lafora disease (LD, OMIM254780, ORPHA501) is a rare neurodegenerative form of epilepsy related to mutations in two proteins: laforin, a dual specificity phosphatase, and malin, an E3-ubiquitin ligase. Both proteins form a functional complex, where laforin recruits specific substrates to be ubiquitinated by malin. However, little is known about the mechanism driving malin-laforin mediated ubiquitination of its substrates. In this work we present evidence indicating that the malin-laforin complex interacts physically and functionally with the ubiquitin conjugating enzyme E2-N (UBE2N). This binding determines the topology of the chains that the complex is able to promote in the corresponding substrates (mainly K63-linked polyubiquitin chains). In addition, we demonstrate that the malin-laforin complex interacts with the selective autophagy adaptor sequestosome 1 (p62). Binding of p62 to the malin-laforin complex allows its recognition by LC3, a component of the autophagosomal membrane. In addition, p62 enhances the ubiquitinating activity of the malin-laforin E3-ubiquitin ligase complex. These data enrich our knowledge on the mechanism of action of the malin-laforin complex as an E3-ubiquitin ligase and reinforces the role of this complex in targeting substrates toward the autophagy pathway. PMID- 26546464 TI - Co-delivery of chemotherapeutics and proteins for synergistic therapy. AB - Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co delivery systems result in markedly enhanced blood stability and in vivo half lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. PMID- 26546465 TI - "Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. AB - The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. PMID- 26546466 TI - Combining antigen and immunomodulators: Emerging trends in antigen-specific immunotherapy for autoimmunity. AB - A majority of current therapies for autoimmune diseases are general immunosuppressants, which can compromise patient response to opportunistic infection and lead to adverse events. Using antigen-specific immunotherapy (ASIT) to selectively disarm autoimmune diseases, without suppressing the global immune response, would be a transformative therapy for patients. ASIT has been used historically in allergy hyposensitization therapy to induce tolerance to an allergen. Similar strategies to induce immune tolerance toward autoantigens responsible for autoimmune disease have been attempted but have yielded limited clinical success. Recent studies of ASIT for autoimmunity have explored combination therapy, combining the disease-causing autoantigen with an immunomodulatory compound. ASIT combination therapy may direct the immune response in an antigen-specific manner, potentially reversing the root cause of autoimmunity while limiting side effects. This review analyzes recent advances in ASIT applied to autoimmune diseases, emphasizing current combination therapies and future strategies. PMID- 26546467 TI - Clinical characteristics of epilepsy of unknown origin in the Rottweiler breed. AB - BACKGROUND: Epilepsy is one of the most common neurological conditions in dogs. Despite that epilepsy appears to be common in the Rottweiler breed, published literature about the phenotype of epilepsy in this breed is lacking. The aim of this questionnaire-based study was to describe the clinical characteristics of epilepsy in the Rottweiler breed including; signalment, pedigree, housing conditions and information about the seizures such as age at onset, seizure type, duration, and progression, as well as number of seizure days (24 h), effect and side effects of anti-epileptic drugs, and potential comorbidities. The diagnosis for epilepsy of unknown origin was based on the following inclusion criteria: >=2 seizure days, starting between 6 months and 7 years of age, no known history of poisoning or serious head trauma, and (when available), pre-study routine serum biochemical parameters were within the reference intervals. RESULTS: A total of 37 cases (23 females and 14 males) were included in the study. The median age at onset of seizures was 36 months (range 8-84 months). The dogs suffered from generalized tonic-clonic seizures, and more than 50 % of the dogs had experienced cluster seizures (>1 seizure in 24 h). The dogs commonly started to seizure while resting (23/36) and/or sleeping (20/36). Only 3 of the 36 dogs experienced seizures during activities such as walking or training. All of the 24/37 (64.9 %) dogs on antiepileptic drugs received phenobarbital. Five dogs needed add-on treatment (n = 5), and of these: one dog was on 3 drugs (phenobarbital, potassium bromid and levetiracetam) (n = 1), three dogs were on phenobarbital and potassium bromide (n = 3), and one dog received phenobarbital and imepitoin (n = 1). Seizure frequency did not necessarily improve following antiepileptic treatment, and for six of 21 (28.6 %) of the dogs, seizure frequency increased. All of the Rottweilers in this study had relatives with epilepsy reported. CONCLUSIONS: The Rottweilers suffering from epilepsy in this study presented with generalized tonic-clonic seizures, and their response to antiepileptic treatment was variable. More than 50 % of the dogs had experienced cluster seizures (>1 seizure in 24 h). PMID- 26546468 TI - The influence of short-interval intracortical facilitation when assessing developmental changes in short-interval intracortical inhibition. AB - OBJECTIVE: Measures of short-interval intracortical inhibition (SICI) can be contaminated by excitatory influences of short-interval intracortical facilitation (SICF), unless examined at individually-optimized interstimulus intervals (ISIs). We hypothesized that age-related differences in SICF would explain previously reported reduced SICI in children and adolescents compared with adults. METHODS: Fifty-one participants, aged 8-29years, underwent transcranial magnetic stimulation. SICF curves were constructed to determine the ISI at which SICF was minimal (i.e. the first trough). SICI curves were constructed at this individually-determined ISI with conditioning stimulus (S1) intensities of 60-110% of active motor threshold. RESULTS: There was no effect of age on the ISI corresponding with the SICF trough. However, there was a main effect of age on the amplitude of the conditioned motor-evoked potential at the different ISIs, such that children aged 8-12years demonstrated greater SICF than those aged 16-18 and 19-21years. There was no effect of age on SICI, and no interaction between age group and S1 intensity. CONCLUSIONS: Compared with that in older adolescents and young adults, SICF is enhanced in children aged 8 12years. Surprisingly, this enhanced SICF does not appear to reduce the degree of SICI that can be evoked at the first trough in this age group. SIGNIFICANCE: This is the first report of enhanced SICF in young children. It remains possible that enhanced SICF may have confounded earlier reports of reduced SICI in children less than 8years. PMID- 26546470 TI - Regulation of electrical activity and neuronal excitability in Helisoma trivolvis by carbon monoxide. AB - Carbon monoxide (CO), like other gaseous neuromodulators, has a dual nature as both a toxic gas and a physiologically relevant signaling molecule. In the nervous system, high concentrations of CO can lead to neuronal injury while lower concentrations are found to be neuroprotective. The number of cellular targets affected by physiological concentrations of CO is rapidly growing and includes ion channels in various cell types. The modulation of ion channels by CO in neurons, however, and the effect it has on neural activity are incompletely understood. Here, the well-characterized buccal neurons, B5 and B19, of the freshwater snail, Helisoma trivolvis, were used to investigate the role that CO plays in regulating spontaneous firing activity and neuronal excitability. Neurons were studied in single-cell culture, thereby removing other signals normally present in the intact nervous system and allowing for the optimal characterization of physiological effects of CO. We found that the CO donor molecule, carbon monoxide releasing molecule-2 (CORM-2), hyperpolarized the resting membrane potential of B5 neurons and silenced their spontaneous firing activity. These effects were mediated through the inhibition of a persistent sodium current. CORM-2 also inhibited neuronal excitability. This effect was mediated by the inhibition of voltage-gated calcium channels by CO. The general findings of CO acting as a hyperpolarizing signal and an inhibitor of neuronal excitability extended to B19 neurons. Taken together, these findings suggest that CO is a potent modulator of ion channels with broad implications for the modulation of neural activity in a wide range of neuron-types. PMID- 26546469 TI - The multifaceted subventricular zone astrocyte: From a metabolic and pro neurogenic role to acting as a neural stem cell. AB - A few decades ago it was discovered that two regions of the adult brain retain the ability to generate new neurons. These regions include the subgranular zone of the hippocampal dentate gyrus and the ventricular-subventricular zone (V-SVZ) located at the border of the lateral ventricle. In the V-SVZ, it was discovered that neural progenitor cells (NPCs) share many features of mature astrocytes and are often referred as V-SVZ astrocytes. We will first describe the markers, the morphology, and the neurophysiological characteristics of the mouse V-SVZ astrocytes. We will then discuss the fact that V-SVZ astrocytes constitute a mixed population with respect to their neurogenic properties, e.g., quiescent versus activated state, neurogenic fate, and transcription factors expression. Finally, we will describe two functions of V-SVZ astrocytes, their metabolic coupling to blood vessels and their neurogenic-supportive role consisting of providing guidance and survival cues to migrating newborn neurons. PMID- 26546471 TI - Changes in the expression of neurotransmitter receptors in Parkin and DJ-1 knockout mice--A quantitative multireceptor study. AB - Parkinson's disease (PD) is a well-characterized neurological disorder with regard to its neuropathological and symptomatic appearance. At the genetic level, mutations of particular genes, e.g. Parkin and DJ-1, were found in human hereditary PD with early onset. Neurotransmitter receptors constitute decisive elements in neural signal transduction. Furthermore, since they are often altered in neurological and psychiatric diseases, receptors have been successful targets for pharmacological agents. However, the consequences of PD-associated gene mutations on the expression of transmitter receptors are largely unknown. Therefore, we studied the expression of 16 different receptor binding sites of the neurotransmitters glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine by means of quantitative receptor autoradiography in Parkin and DJ-1 knockout mice. These knockout mice exhibit electrophysiological and behavioral deficits, but do not show the typical dopaminergic cell loss. We demonstrated differential changes of binding site densities in eleven brain regions. Most prominently, we found an up-regulation of GABA(B) and kainate receptor densities in numerous cortical areas of Parkin and DJ-1 knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the Parkin knockout mice. The alterations of three different glutamate receptor types may indicate the potential relevance of the glutamatergic system in the pathogenesis of PD. Furthermore, the cholinergic M1, M2 and nicotinic receptors as well as the adrenergic alpha2 and the adenosine A(2A) receptors showed differentially increased densities in Parkin and DJ-1 knockout mice. Taken together, knockout of the PD-associated genes Parkin or DJ-1 results in differential changes of neurotransmitter receptor densities, highlighting a possible role of altered non-dopaminergic, and in particular of glutamatergic neurotransmission in PD pathogenesis. PMID- 26546472 TI - Rapid lung MRI in children with pulmonary infections: Time to change our diagnostic algorithms. AB - BACKGROUND: To determine the diagnostic utility of a new rapid MRI protocol, as compared with computed tomography (CT) for the detection of various pulmonary and mediastinal abnormalities in children with suspected pulmonary infections. METHODS: Seventy-five children (age range of 5 to 15 years) with clinically suspected pulmonary infections were enrolled in this prospective study, which was approved by the institutional ethics committee. All patients underwent thoracic MRI (1.5T) and CT (64 detector) scan within 48 h of each other. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI were evaluated with CT as a standard of reference. Inter-observer agreement was measured with the kappa coefficient. RESULTS: MRI with a new rapid MRI protocol demonstrated sensitivity, specificity, PPV, and NPV of 100% for detecting pulmonary consolidation, nodules (>3 mm), cyst/cavity, hyperinflation, pleural effusion, and lymph nodes. The kappa-test showed almost perfect agreement between MRI and multidetector CT (MDCT) in detecting thoracic abnormalities (k = 0.9). No statistically significant difference was observed between MRI and MDCT for detecting thoracic abnormalities by the McNemar test (P = 0.125). CONCLUSION: Rapid lung MRI was found to be comparable to MDCT for detecting thoracic abnormalities in pediatric patients with clinically suspected pulmonary infections. It has a great potential as the first line cross-sectional imaging modality of choice in this patient population. However, further studies will be helpful for confirmation of our findings. PMID- 26546473 TI - Smoking habits and clinical patterns can alter the inflammatory infiltrate in oral lichenoid lesions. AB - OBJECTIVE: The present immunohistochemical study aimed to investigate the possible correlation between demographic variables and clinical presentation of oral lichenoid lesions (OLL), in addition to the potential effects of these variables and smoking status on OLL inflammatory infiltrate. STUDY DESIGN: A total of 53 patients with OLL were assigned, according to their smoking status at the time of diagnosis, to either a smokers group (n = 27) or a nonsmokers group (n = 26). Demographic and clinical data, including the site and pattern of the OLL, symptoms, and medical history, were analyzed. Immunohistochemical expression of clusters of differentiation, including CD3, CD4, CD8, CD68, and CD1a, was compared between the two groups. RESULTS: Gingival involvement in OLL was found to be significantly associated with older age. Buccal mucosa as the sole OLL site showed a significantly higher expression of CD3+ cells compared with other sites (P < .05). OLL presenting as a reticular type alone was significantly associated with less CD3+ expression (P < .05), whereas a significantly higher CD1a+ expression was seen with plaque-like type OLL (P < .05). Smoking was significantly associated with less expression of macrophages (CD68+ cells) and less clinical symptoms (P < .05 and P < .01, respectively). CONCLUSION: The inflammatory infiltrate in OLL can be affected by their clinical distribution and presentation. Smoking reduces the expression of macrophages in OLL, and this may alter the immune surveillance and the mechanisms of malignant transformation. PMID- 26546474 TI - Emission Timetable and Quantitative Patterns of Wound-Induced Volatiles Across Different Leaf Damage Treatments in Aspen (Populus Tremula). AB - Plant-feeding herbivores can generate complex patterns of foliar wounding, but it is unclear how wounding-elicited volatile emissions scale with the severity of different wounding types, and there is no common protocol for wounding experiments. We investigated the rapid initial response to wounding damage generated by different numbers of straight cuts and punctures through leaf lamina as well as varying area of lamina squeezing in the temperate deciduous tree Populus tremula. Wounding-induced volatile emission time-courses were continuously recorded by a proton-transfer-reaction time-of-flight mass spectrometer. After the mechanical wounding, an emission cascade was rapidly elicited resulting in sequential emissions of key stress volatiles methanol, acetaldehyde, and volatiles of the lipoxygenase pathway, collectively constituting more than 97% of the total emission. The maximum emission rates, reached after one to three minutes after wounding, and integrated emissions during the burst were strongly correlated with the severity in all damage treatments. For straight cuts and punch hole treatments, the emissions per cut edge length were constant, indicating a direct proportionality. Our results are useful for screening wounding-dependent emission capacities. PMID- 26546475 TI - Environmental impact and risk assessments and key factors contributing to the overall uncertainties. AB - There is a significant number of nuclear and radiological sources that have contributed, are still contributing, or have the potential to contribute to radioactive contamination of the environment in the future. To protect the environment from radioactive contamination, impact and risk assessments are performed prior to or during a release event, short or long term after deposition or prior and after implementation of countermeasures. When environmental impact and risks are assessed, however, a series of factors will contribute to the overall uncertainties. To provide environmental impact and risk assessments, information on processes, kinetics and a series of input variables is needed. Adding problems such as variability, questionable assumptions, gaps in knowledge, extrapolations and poor conceptual model structures, a series of factors are contributing to large and often unacceptable uncertainties in impact and risk assessments. Information on the source term and the release scenario is an essential starting point in impact and risk models; the source determines activity concentrations and atom ratios of radionuclides released, while the release scenario determine the physico-chemical forms of released radionuclides such as particle size distribution, structure and density. Releases will most often contain other contaminants such as metals, and due to interactions, contaminated sites should be assessed as a multiple stressor scenario. Following deposition, a series of stressors, interactions and processes will influence the ecosystem transfer of radionuclide species and thereby influence biological uptake (toxicokinetics) and responses (toxicodynamics) in exposed organisms. Due to the variety of biological species, extrapolation is frequently needed to fill gaps in knowledge e.g., from effects to no effects, from effects in one organism to others, from one stressor to mixtures. Most toxtests are, however, performed as short term exposure of adult organisms, ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems. PMID- 26546476 TI - Evaluation of a Drowning Prevention Program Based on Testimonial Videos: A Randomized Controlled Trial. AB - OBJECTIVE: Unintentional drowning is the most common cause of childhood death in rural China. Global intervention efforts offer mixed results regarding the efficacy of educational programs. METHODS: Using a randomized controlled design, we evaluated a testimonial-based intervention to reduce drowning risk among 280 3rd- and 4th-grade rural Chinese children. Children were randomly assigned to view either testimonials on drowning risk (intervention) or dog-bite risk (control). Safety knowledge and perceived vulnerability were measured by self report questionnaires, and simulated behaviors in and near water were assessed with a culturally appropriate dollhouse task. RESULTS: Children in the intervention group had improved children's safety knowledge and simulated behaviors but not perceived vulnerability compared with controls. CONCLUSIONS: The testimonial-based intervention's efficacy appears promising, as it improved safety knowledge and simulated risk behaviors with water among rural Chinese children. PMID- 26546477 TI - Edoxaban: A Review in Deep Vein Thrombosis and Pulmonary Embolism. AB - Edoxaban (Lixiana, Savaysa) is an oral, direct factor Xa inhibitor which has recently been approved for use in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) [collectively, venous thromboembolism (VTE)] and for the prevention of recurrent VTE. This article reviews the pharmacological properties of edoxaban as well as its tolerability and therapeutic efficacy in the treatment and prevention of recurrent VTE events. As demonstrated in the pivotal Hokusai VTE phase III trial, once-daily edoxaban after initial treatment with heparin was non-inferior to standard therapy with heparin/warfarin in preventing recurrent VTE events and was associated with a significantly lower risk of clinically relevant bleeding than the traditional therapy. Edoxaban shares the advantages of other direct oral anticoagulants (DOACs) over traditional therapies, including the lack of requirement for routine coagulation monitoring, a rapid onset and offset of action, and few drug-drug interactions. It offers the convenience of once-daily dosing, can be taken without regard to food and allows for a dose reduction in patients with certain clinical features, such as moderate renal impairment or low body weight. In conclusion, edoxaban represents an effective and potentially safer alternative to traditional vitamin K antagonist therapy for the treatment and prevention of recurrent VTE. Its recent approval expands the range of DOAC agents for recurrent VTE, further facilitating treatment individualization. PMID- 26546478 TI - Value of preoperative 6-minute walk test for predicting postoperative pulmonary complications. AB - OBJECTIVES: The objective of this study was to determine the performance of preoperative 6-minute walk test (6MWT) for predicting postoperative pulmonary complications (PPC) in high risk patients undergoing elective surgery under general anesthesia. METHODS: A prospective cohort study was conducted in patients scheduled to undergo elective thoracic or nonthoracic surgery and indicated for preoperative pulmonary evaluation in Songklanagarind Hospital, Songkhla, Thailand. Preoperative spirometry, 6MWT were done and 30-day PPC were recorded. The multiple regression analysis and receiver operating characteristic (ROC) curves were used to analyze the variables and to compare the performance of 6MWT and spirometry tests. RESULTS: A total of 78 participants were recruited into the study. 6MWT was done completely in all cases without any complications. Among these tests, 14 cases (17.9%) had contraindications to spirometry and two cases were unable to achieve the criteria for acceptable efforts. PPC developed in 17 cases (21%) with a high mortality (17.7%). A multiple regression analysis showed elderly, poor general health status, smoking history, low level of the mean value of forced expiratory volume in 1 second (FEV1) % predicted (by spirometry) and shorter 6-minute walk distance (6MWD) were the independent factors associated with PPC. Patients developing PPC had a significantly lower preoperative 6MWD compared with patients without PPC (256.0 +/- 48.0 versus 440.0 +/- 117.1 meters, p < 0.001). 6MWD of ?325 meters was a threshold for predicting PPC with 77% sensitivity and 100% specificity, and had a good predictive value for PPC similar to that for the FEV1 %. CONCLUSIONS: Preoperative 6MWT is a very useful alternative test for predicting PPC in high risk patients scheduled to undergo surgery under GA. PMID- 26546481 TI - Surgical considerations for patients with metastatic renal cell carcinoma. AB - Among patients with renal cell carcinoma (RCC), 25-30% present with metastatic disease at the time of initial diagnosis. Despite the ever-increasing array of treatment options available for these patients, surgery remains one of the cornerstones of therapy. Proper patient selection for cytoreductive surgery is paramount to its effective use in the management of patients with metastatic RCC despite the decrease in reported morbidity rates. We explore the evolving role cytoreductive surgery in metastatic RCC spanning the immunotherapy era to the targeted therapy era. Despite significant advances in the management of patients with metastatic RCC, further evidence on the definitive role of cytoreductive surgery in the targeted therapy era is awaited through large randomized trials. PMID- 26546479 TI - Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology. AB - Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID- 26546480 TI - Rapid immunocytochemistry based on alternating current electric field using squash smear preparation of central nervous system tumors. AB - The role of intraoperative pathological diagnosis for central nervous system (CNS) tumors is crucial for neurosurgery when determining the surgical procedure. Especially, treatment of carmustine (BCNU) wafers requires a conclusive diagnosis of high-grade glioma proven by intraoperative diagnosis. Recently, we demonstrated the usefulness of rapid immunohistochemistry (R-IHC) that facilitates antigen-antibody reaction under alternative current (AC) electric field in the intraoperative diagnosis of CNS tumors; however, a higher proportion of water and lipid in the brain parenchyma sometimes leads to freezing artifacts, resulting in poor quality of frozen sections. On the other hand, squash smear preparation of CNS tumors for cytology does not affect the frozen artifacts, and the importance of smear preparation is now being re-recognized as being better than that of the tissue sections. In this study, we established the rapid immunocytochemistry (R-ICC) protocol for squash smears of CNS tumors using AC electric field that takes only 22 min, and demonstrated its usefulness for semi quantitative Ki-67/MIB-1 labeling index and CD 20 by R-ICC for intraoperative diagnosis. R-ICC by AC electric field may become a substantial tool for compensating R-IHC and will be applied for broad antibodies in the future. PMID- 26546482 TI - Patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities. AB - PURPOSE: The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34. PATIENTS AND METHODS: In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes. RESULTS: We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08). CONCLUSIONS: ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes. PMID- 26546483 TI - Left Ventricular Systolic Longitudinal Function as Predictor of Outcome in Patients With Sepsis. AB - BACKGROUND: In sepsis, whether the assessment of left ventricular global longitudinal systolic strain (GLS) is feasible and prognostically relevant remains controversial. METHODS AND RESULTS: Consecutive patients admitted to a high-dependency observational unit with sepsis or septic shock were evaluated. Left ventricular ejection fraction (EF) by planimetry and peak GLS by 2D speckle tracking were available at admission in 115 of 149 (77%) patients. Compared with patients included in the study, those excluded (n=34, 23%) showed higher proportion of chronic obstructive pulmonary disease (P<0.01), but with comparable clinical characteristics and mortality rates. GLS showed lowest variability for low EF and highest for higher EF. By day-28 follow-up, all-cause mortality was 30% (n=34 and n=19 within 7 days from hospitalization). GLS and EF were both more abnormal in deceased than in those alive by day-28 follow-up (both P<0.05, findings consistent using day-7 follow-up data). GLS showed a borderline relationship with mortality by day-28 follow-up (hazard ratio 1.16/%, P=0.05), whereas EF did not (hazard ratio 0.99/%, P=0.63) accounting for age; the lack of association of all-cause mortality with EF was consistent at day-7 follow-up (hazard ratio 0.94/%, P=0.9), whereas more abnormal GLS correlated significantly with higher mortality rate (hazard ratio 1.30/%, P=0.03) independent to age. CONCLUSIONS: In patients with sepsis assisted in a high-dependency observational unit, feasibility of assessments of left ventricular EF and GLS within 24 h from the hospitalization was acceptable and EF showed no prognostic relevance, whereas GLS showed a correlation with mortality rate potentially relevant in shorter more than in longer follow-ups. PMID- 26546484 TI - Assessing Contractile Function When Ejection Fraction Is Normal: A Case for Strain Imaging. PMID- 26546485 TI - Immune regulatory and neuroprotective properties of preimplantation factor: From newborn to adult. AB - Embryonic-maternal interaction from the earliest stages of gestation has a key, sustained role in neurologic development, persisting into adulthood. Early adverse events may be detrimental in adulthood. Protective factors present during gestation could significantly impact post-natal therapy. The role of PreImplantation Factor (PIF) within this context is herein examined. Secreted by viable early embryos, PIF establishes effective embryonic-maternal communication and exerts essential trophic and protective roles by reducing oxidative stress and protein misfolding and by blunting the nocive let-7 microRNA related pathway. PIF's effects on systemic immunity lead to comprehensive immune modulation, not immune suppression. We examine PIF's role in protecting embryos from adverse maternal environment, which can lead to neurological disorders that may only manifest post-nataly: Synthetic PIF successfully translates endogenous PIF features in both pregnant and non-pregnant clinically relevant models. Specifically PIF has neuroprotective effects in neonatal prematurity. In adult relapsing-remitting neuroinflammation, PIF reverses advanced paralysis while promoting neurogenesis. PIF reversed Mycobacterium smegmatis induced brain infection. In graft-vs.-host disease, PIF reduced skin ulceration, liver inflammation and colon ulceration while maintaining beneficial anti-cancer, graft vs.-leukemia effect. Clinical-grade PIF has high-safety profile even at supraphysiological doses. The FDA awarded Fast-Track designation, and university sponsored clinical trials for autoimmune disorder are ongoing. Altogether, PIF properties point to its determining regulatory role in immunity, inflammation and transplant acceptance. Specific plans for using PIF for the treatment of complex neurological disorders (ie. traumatic brain injury, progressive paralysis), including neuroprotection from newborn to adult, are presented. PMID- 26546486 TI - Comparative Effectiveness of Insecticides for Use Against the House Fly (Diptera: Muscidae): Determination of Resistance Levels on a Malaysian Poultry Farm. AB - In this study, the toxicology of two commercial larvicides--cyromazine (Neporex 50SP) and ChCy (combination of chlorpyrifos and cypermethrin, Naga 505)--and five commercial adulticides--thiamethoxam (Agita 10WG), cyfluthrin (Responsar WP), lambda-cyhalothrin (Icon 2.8EC), fipronil (Regent 50SC), and imidacloprid (Toxilat 10WP)--was examined against the WHO/VCRU (World Health Organization/ Vector Control Research Unit) susceptible strain and the AYTW (Ayer Tawar) field strain of house fly, Musca domestica L. These pesticides were administered topically, in the diet, or as a dry residue treatment on plywood. Probit analysis using at least five concentrations and the concentration that was lethal to 50% (LC(50)) of the organisms was applied to compare the toxicology and resistance levels of the AYTW population to different insecticides. In the larvicide laboratory study, ChCy was more effective than cyromazine, with a significantly lower LC(50) value when administered topically or in the diet, although the AYTW population was susceptible to both larvicides with a resistance ratio (RR) <10. For the adulticide laboratory study, cyfluthrin and fipronil exhibited the lowest LC50 values of the adulticides, indicating that they are both effective at controlling adult flies, although lambda-cyhalothrin showed moderate resistance (RR = 11.60 by topical application; 12.41 by plywood treatment). Further investigation of ChCy, cyromazine, cyfluthrin, and fipronil under field conditions confirmed that ChCy and cyromazine strikingly reduced larval density, and surprisingly, ChCy also exhibited adulticidal activity, which significantly reduced adult fly numbers compared with the control group. Cyfluthrin and fipronil were also confirmed to be effective, with a significant reduction in adult fly numbers compared with the control group. PMID- 26546487 TI - Individual and Joint Acute Toxicities of Selected Insecticides Against Bombyx mori (Lepidoptera: Bombycidae). AB - As widely used pesticides, organophosphate, pyrethroid, and neonicotinoid insecticides have different modes of action. In the present study, we evaluated individual and joint acute toxicities of two organophosphates, two pyrethroids, and two neonicotinoids against the second-instar silkworm by feeding silkworm with the insecticide-treated mulberry leaves. The 96-h lethal concentration 50 (LC(50)) values of chlorpyrifos, acephate, imidacloprid, thiamethoxam, cypermethrin, and deltamethrin against silkworm were 3.45 (2.95-4.31), 44.45 (39.34-48.56), 1.27 (1.19-1.35), 2.38 (2.19-2.54), 0.36 (0.30-0.43), and 0.037 (0.033-0.041) mg/liter, respectively. Moreover, the 96-h LC(50) values of 50:50 binary mixtures of insecticides against silkworm ranged from 0.048 (0.043-0.054) to 3.52 (2.09-4.51) mg/liter. In addition, the combination coefficient (Q) values of all tested mixtures ranged from 0.36 to 3.37. According to the obtained Q values, the binary mixture of deltamethrin-chlorpyrifos showed antagonistic effects at 96-h interval, while the other binary mixtures had additive effects. Taken together, our results provided valuable guidelines in assessing the ecological risk of these insecticide mixtures against silkworm. PMID- 26546488 TI - Resistance of Dusky Cotton Bug, Oxycarenus hyalinipennis Costa (Lygaidae: Hemiptera), to Conventional and Novel Chemistry Insecticides. AB - The dusky cotton bug, Oxycarenus hyalinipennis Costa (Lygaidae: Hemiptera), is polyphagous in nature and has become one of the severe sucking pests of cotton in Pakistan. O. hyalinipennis has the potential to develop resistance to a number of insecticides, and as a result, O. hyalinipennis outbreaks occur. There is no previous study from Pakistan regarding O. hyalinipennis resistance to insecticides. Therefore, the aim of this study was to assess the resistance of different field populations of O. hyalinipennis to conventional (bifenthrin, deltamethrin, lambda-cyhalothrin, profenofos, triazophos) and novel chemistry (emamectin benzoate, spinosad, chlorfenapyr, imidacloprid, and nitenpyram) insecticides. Five populations of O. hyalinipennis, collected from Multan, Khanewal, Muzaffargarh, Lodhran, and Bahawalpur, were tested for resistance to selected insecticides by the leaf dip method. For three pyrethroids, the resistance ratios were in the range of 14- to 30-fold for bifenthrin, 2.14- to 8.41-fold for deltamethrin, and 9.12- to 16-fold for lambda-cyhalothrin, compared with the laboratory susceptible strain (Lab-PK). For two organophosphates, the range of resistance ratios was 12- to 14-fold for profenofos and 9.04- to 15-fold for triazophos. For five novel chemistry insecticides, the range of resistance ratios was 4.68- to 9.83-fold for emamectin benzoate, 6.38- to 17-fold for spinosad, 16- to 46-fold for chlorfenapyr, 11- to 22-fold for imidacloprid, and 1.32- to 11-fold for nitenpyram. Regular assessment of resistance to insecticides and integrated management plans like judicious use of insecticides and rotation of insecticides along with different modes of action are required to delay resistance development in O. hyalinipennis. PMID- 26546489 TI - Baseline Susceptibility of Lygus lineolaris (Hemiptera: Miridae) to Novaluron. AB - Tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), populations were collected from field locations in the Mississippi River Delta of Arkansas, Louisiana, and Mississippi. Third-instar F(1) nymphs from each field location, in addition to a laboratory colony, were screened for susceptibility to novaluron. Both a glass vial bioassay and a diet-incorporated bioassay used dose-response regression lines to calculate LC(50) and LC(90) values for novaluron. Mean LC(50s) for glass vial bioassays ranged from 44.70 +/- 3.58 to 66.54 +/- 4.19 MUg/vial, while mean LC(50s) for diet-incorporated bioassays ranged from 12.10 +/ 0.77 to 17.63 +/- 2.42 MUg/200 ml of artificial diet. A comparison of LC(50) values from the same field population screened using both bioassay methods failed to show a relationship. LC(50) values from field locations were compared with a historically susceptible population from Crossett, AR. Results indicated that considerable variability in susceptibility to novaluron exists within field populations of tarnished plant bugs across the Delta, including some locations with lower LC(50) values than a historically susceptible population. PMID- 26546490 TI - Sedative and echocardiographic effects of dexmedetomidine combined with butorphanol in healthy dogs. AB - OBJECTIVES: To evaluate the echocardiographic variables and sedation after two dosages of dexmedetomidine combined with butorphanol in healthy dogs. ANIMALS: Fourteen healthy dogs. METHODS: The dogs received dexmedetomidine 5 mcg/kg IM and butorphanol 0.4 mg/kg (low dose (LD), n = 6) or dexmedetomidine 10 mcg/kg IM and butorphanol 0.4 mg/kg (recommended dose (RD), n = 8). Sedation scoring, noninvasive blood pressure measurement, and echocardiography were performed before sedation at baseline, at 20 minutes (T20), and 60 minutes (T60) after drug administration. RESULTS: The median sedation scores were increased at both T20 and T60 in the RD group, and at T60 in the LD group, compared with baseline (p < 0.0001, p = 0.012). At T60, the RD dogs were more sedated than the LD dogs (p = 0.0093). The median cardiac output (CO) decreased at both T20 (63%) and T60 (65%) in the RD group and at T60 (42%) in the LD group, compared with baseline (p = 0.0011, p = 0.0055). The median heart rate (HR) was decreased at both T20 and T60 in the RD group and at T60 in the LD group, compared with baseline (p = 0.0009, p = 0.0001). In both RD and LD dogs, valvular regurgitation developed and was identified by color Doppler imaging. CONCLUSIONS: There were significant hemodynamic changes, mainly related to HR and indices of systolic function, following administration of dexmedetomidine in these healthy dogs. The changes also included decreases in systolic function and CO, as well as appearance of 'new' valvular regurgitation. Caution should be used when considering dexmedetomidine for sedation in dogs with, or being screened for, cardiovascular disease. PMID- 26546495 TI - Colloidal CsPbBr3 Perovskite Nanocrystals: Luminescence beyond Traditional Quantum Dots. AB - Traditional CdSe-based colloidal quantum dots (cQDs) have interesting photoluminescence (PL) properties. Herein we highlight the advantages in both ensemble and single-nanocrystal PL of colloidal CsPbBr3 nanocrystals (NCs) over the traditional cQDs. An ensemble of colloidal CsPbBr3 NCs (11 nm) exhibits ca. 90 % PL quantum yield with narrow (FWHM=86 meV) spectral width. Interestingly, the spectral width of a single-NC and an ensemble are almost identical, ruling out the problem of size-distribution in PL broadening. Eliminating this problem leads to a negligible influence of self-absorption and Forster resonance energy transfer, along with batch-to-batch reproducibility of NCs exhibiting PL peaks within +/-1 nm. Also, PL peak positions do not alter with measurement temperature in the range of 25 to 100 degrees C. Importantly, CsPbBr3 NCs exhibit suppressed PL blinking with ca. 90 % of the individual NCs remain mostly emissive (on-time >85 %), without much influence of excitation power. PMID- 26546496 TI - De-escalation of Infliximab Maintenance Therapy from 8- to 10-week Dosing Interval Based on Faecal Calprotectin in Patients with Crohn's Disease. PMID- 26546497 TI - Identification of a mutation causing hypertrophic cardiomyopathy using whole exome sequencing: A proof-of-concept. PMID- 26546498 TI - Prevalence and clinical characteristics of degenerative mitral stenosis. AB - BACKGROUND: Degenerative mitral stenosis (DMS) is found in the elderly population. However, there are a few reports regarding the prevalence rate of DMS and, its clinical characteristics. The aim of this study was to determine the relationship between age, gender, and the prevalence rate of DMS. METHODS: Patients with DMS and rheumatic mitral stenosis (RMS) were searched retrospectively in consecutive patients who underwent echocardiography from January 2011 to December 2013 in a community hospital. DMS was defined as presence of both turbulent antegrade flow with a mean transmitral pressure gradient (PG) of >=2mmHg and mitral annular calcification without restriction of leaflets tip motion. RESULTS: We identified 19 patients (17 female and 2 male) with DMS (0.22%) and 19 patients with RMS in 8683 patients. The prevalence rate of DMS significantly increased with aging, especially in patients >90 years old. There was no significant difference in the prevalence rates of RMS among the age groups. Patients with DMS were older (86+/-8 years vs. 73+/-10 years, p<0.01) and had higher rates of hypertension and aortic stenosis, larger left ventricular mass index, and mean PG of aortic valve, smaller aortic valve area, less degree of left atrial dilatation, and lower rate of atrial fibrillation, compared with those values in patients with RMS. CONCLUSIONS: DMS is rare (0.22%) and almost exclusively found in females in routine echocardiography. The prevalence of DMS increases with aging to 2.5% in patients >90 years of age, and DMS is often associated with aortic valve stenosis. PMID- 26546499 TI - Comparative efficacy and acceptability of combined antipsychotics and mood stabilizers versus individual drug classes for acute mania: Network meta analysis. AB - OBJECTIVES: Recent network meta-analyses of drug treatments for acute mania have only evaluated the efficacy and acceptability of individual drug treatments. The relative efficacy and acceptability of combined drug treatment has not been assessed. METHODS: Double-blind drug trials in acute mania were identified using a systematic search strategy. We recorded numbers of patients enrolled, endpoints for efficacy (changes in mania rating scales, numbers of responders) and acceptability (numbers of dropouts) and treatment administered (categorized as antipsychotic, mood stabilizer, combined antipsychotic/mood stabilizer or placebo). Data were analyzed using a random effects frequentist network meta analysis. RESULTS: All three drug categories were more effective than placebo. Antipsychotics and combined antipsychotic/mood stabilizer were significantly more effective than mood stabilizers for changes in mania rating scales. Combined antipsychotic/mood stabilizer was significantly more effective than mood stabilizers and antipsychotics for responder rate. Dropout rates were significantly lower for antipsychotics compared with placebo and mood stabilizers. Combined antipsychotic/mood stabilizer had the highest probability of being the best treatment based on change in mania rating scales (96.1% for all mania scales; 85.5% for Young Mania Rating Scale), and 99.3% for being the best treatment for responders. Antipsychotics had 82.0% probability as the best treatment to minimize dropouts. CONCLUSION: Combined antipsychotic/mood stabilizer appears to have efficacy advantages over antipsychotic or mood stabilizer monotherapy in acute mania, and should be considered as first line therapy. PMID- 26546500 TI - The prevalence and age of onset of psychiatric disorders in Australian men. AB - OBJECTIVE: Given the burden of common psychiatric disorders and their consequent service and planning requirements, it is important to have a thorough knowledge of their distribution and characteristics in the population. Thus, we aimed to report the prevalence and age of onset of mood, anxiety and substance-use disorders in an age-stratified representative sample of Australian men. METHOD: Psychiatric disorders (mood, anxiety and substance-use disorders) were diagnosed utilising a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Non-Patient Edition) for 961 men aged 24-98 years enrolled in the Geelong Osteoporosis Study. The lifetime and current prevalence of these disorders was determined from the study population and standardised to 2006 census data for Australia. RESULTS: Approximately one in three men (28.8%, 95% confidence interval [CI] = [26.8%, 30.8%]) reported a lifetime history of any psychiatric disorder, with mood disorders (18.2%, 95% CI = [15.2%, 21.2%]) being more prevalent than anxiety (7.2%, 95% CI = [5.0%, 9.4%]) and substance-use disorders (12.9%, 95% CI = [9.7%, 16.0%]). Approximately 8.7% (95% CI = [7.5%, 10.0%]) were identified as having a current disorder, with 3.8% (95% interquartile range [IQR] = [2.2%, 5.4%]), 2.4% (95% CI = [1.1%, 3.8%]) and 3.4% (95% CI = [1.8%, 4.9%]) meeting criteria for current mood, anxiety and substance-use disorders, respectively. The median age of onset for mood disorders was 37.5 years (IQR = 27.0-48.0 years), 25.0 years (IQR = 20.0-40.3 years) for anxiety and 22.0 years (IQR = 18.0-34.3 years) for substance-use disorders. CONCLUSION: This study reports the lifetime and current prevalence of psychiatric disorders in the Australian male population. These findings emphasise the extent of the burden of these disorders in the community. PMID- 26546501 TI - Associations between recent gay-related stressful events, emotional distress, social support and unprotected anal intercourse behavior among Chinese men who have sex with men. AB - BACKGROUND: This study was designed to assess the levels of and associations between gay-related stressful events, social support, emotional distress and the number of unprotected anal intercourse partners among Chinese men who have sex with men. METHODS: Using a respondent-driven sampling method, 807 men who have sex with men were recruited in urban areas of northeast China and data were collected via face-to-face interviews. Gay-related stressful events were measured using the Gay-Related Stressful Life Events Scale; levels of depression, anxiety symptoms and social support were measured using the Self-Rating Depression Scale, the Self-Rating Anxiety Scale and the Social Support Rating Scale, respectively. RESULTS: Over a quarter of study participants experienced gay-related stressful events during the preceding 3 months. Their average Self-Rating Depression Scale, Self-Rating Anxiety Scale and Social Support scores differed significantly from the national norm. Gay-related stressful events significantly correlated with anxiety (r = 0.167, p < 0.001), depression (r = 0.165, p < 0.001), social support (r = -0.107, p = 0.002) and number of unprotected anal intercourse partners (r = 0.13, p < 0.001), showing a clear dose-response relationship. CONCLUSION: Gay related stressful events are common and are significantly associated with emotional distress, lack of social support and high-risk sexual behaviors among Chinese men who have sex with men. Multifaceted approaches are warranted to increase social support and reduce intolerance toward homosexual behaviors and to reduce risky sexual behaviors related to the rapid HIV epidemic among men who have sex with men population in China. PMID- 26546502 TI - Steroidal saponins from stems and leaves of Paris polyphylla var. yunnanensis. AB - Phytochemical investigation of the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of 12 steroidal saponins, chonglouosides SL-9-SL-20, which had not been described previously, along with 13 known compounds. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. Four of the twelve steroidal saponins possessed three steroidal aglycones which have not been reported in nature. Steroidal saponins were also evaluated for their cytotoxicities against two human cancer cell lines (HepG2 and HEK293) and anti-HCV effects. One known steroidal saponin was the most cytotoxic compound overall with IC50 values of 2.9 +/- 0.5 MUM and 5.0 +/- 0.6 MUM against HepG2 and HEK293 cell lines, respectively, while none showed anti-HCV activity at a concentration of 20 MUM. PMID- 26546503 TI - Spinal glial activation and oxidative stress are alleviated by treatment with curcumin or coenzyme Q in sickle mice. PMID- 26546504 TI - The role of CD44 in fetal and adult hematopoietic stem cell regulation. AB - Throughout development, hematopoietic stem cells migrate to specific microenvironments, where their fate is, in part, extrinsically controlled. CD44 standard as a member of the cell adhesion molecule family is extensively expressed within adult bone marrow and has been previously reported to play important roles in adult hematopoietic regulation via CD44 standard-ligand interactions. In this manuscript, CD44 expression and function are further assessed and characterized on both fetal and adult hematopoietic stem cells. Using a CD44(-/-) mouse model, conserved functional roles of CD44 are revealed throughout development. CD44 is critical in the maintenance of hematopoietic stem and progenitor pools, as well as in hematopoietic stem cell migration. CD44 expression on hematopoietic stem cells as well as other hematopoietic cells within the bone marrow microenvironment is important in the homing and lodgment of adult hematopoietic stem cells isolated from the bone/bone marrow interface. CD44 is also involved in fetal hematopoietic stem cell migration out of the liver, via a process involving stromal cell-derived factor-1alpha. The absence of CD44 in neonatal bone marrow has no impact on the size of the long-term reconstituting hematopoietic stem cell pool, but results in an enhanced long-term engraftment potential of hematopoietic stem cells. PMID- 26546506 TI - Septic arthritis due to Clostridium ramosum. AB - OBJECTIVES: Clostridium species are anaerobic bacilli that are rarely reported as etiologic agents of infectious arthritis. Previous cases of arthritis caused by Clostridium ramosum have not been reported. We describe the first 2 cases of C. ramosum arthritis. METHODS: We reviewed the etiology of arthritis in our hospital during the previous 15 years. RESULTS: Both patients had underlying immunocompromising conditions and their infections involved a joint with preexisting disease: patient 1 had rheumatic arthritis and a prosthetic joint; patient 2, chronic renal failure on dialysis and hip osteoarthritis. The infection was hematogenously acquired and the course was indolent but destructive in both the cases. Management included open arthrotomy and resection arthroplasty. The infection had a persisting and relapsing course, and prolonged antibiotic treatment was required. In the literature review, we found 55 previous cases of arthritis caused by Clostridium species between 1966 and 2014; Clostridium perfringens was the most common infecting species; the infection was traumatically acquired in most of the cases. A total of 15 patients have been described with infections caused by C. ramosum; none had septic arthritis. The majority were elderly or immunocompromised adults. Proper collection, transportation and processing of clinical specimens is essential for diagnosing clostridial infections. More information about the best management of clostridial arthritis are needed. CONCLUSIONS: We describe the first 2 cases of septic arthritis caused by C. ramosum. They shared several pathogenic and clinical features. The possibility of anaerobic arthritis should always be considered when collecting diagnostic specimens. An increasing number of clostridial arthritis cases are likely to be diagnosed in future years. PMID- 26546505 TI - SIRT2 inhibition exacerbates neuroinflammation and blood-brain barrier disruption in experimental traumatic brain injury by enhancing NF-kappaB p65 acetylation and activation. AB - Sirtuin 2 (SIRT2) is a member of the sirtuin family of NAD(+) -dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI). We investigated the effects of SIRT2 inhibition on experimental TBI using the controlled cortical impact (CCI) injury model. Adult male mice underwent CCI or sham surgery. A selective brain-permeable SIRT2 inhibitor, AK-7, was administrated 30 min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with AK-7 (20 mg/kg), compared with the vehicle group, following TBI (p < 0.05 at 1 day and p < 0.05 at 3 days, respectively). Concomitantly, AK-7 administration greatly worsened neurobehavioral deficits on days 3 and 7 after CCI. Furthermore, blood-brain barrier disruption and matrix metalloproteinases (MMP)-9 activity increased following SIRT2 inhibition. AK-7 treatment increased TBI-induced microglial activation both in vivo and in vitro, accompanied by a large increase in the expression and release of inflammatory cytokines. Mechanistically, SIRT2 inhibition increased both K310 acetylation and nuclear translocation of NF-kappaB p65, leading to enhanced NF-kappaB activation and up-regulation of its target genes, including aquaporin 4 (AQP4), MMP-9, and pro-inflammatory cytokines. Together, these data demonstrate that SIRT2 inhibition exacerbates TBI by increasing NF-kappaB p65 acetylation and activation. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. SIRT2 is a member of the sirtuin family of NAD+-dependent protein deacetylases. Our study suggests that the SIRT2 inhibitor AK-7 exacerbates traumatic brain injury (TBI) via a potential mechanism involving increased acetylation and nuclear translocation of NF-kappaB p65, resulting in up-regulation of NF-kappaB target genes, including aquaporin 4 (AQP4), matrix metalloproteinase 9 (MMP-9), and pro-inflammatory cytokines. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. PMID- 26546507 TI - Promoting Policy and Environmental Change in Faith-Based Organizations: Outcome Evaluation of a Mini-Grants Program. AB - High rates of heart disease, cancer, and stroke exist in rural South Georgia where the Emory Prevention Research Center's Cancer Prevention and Control Research Network provided mini-grant funding to six churches to implement policy and environmental change to promote healthy eating and physical activity. This study sought to determine whether perceptions of the health promotion environment changed over time and whether perceived environmental change was associated with healthy behavior at church and in general. This study used a single-group pre post design with 1-year follow-up. Parishioners (N = 258) completed self administered questionnaires assessing perceptions of the church health promotion environment relative to healthy eating and physical activity, eating behavior and intention to use physical activity facilities at church, and eating and physical activity behaviors generally. Results indicate that perceived improvements in church nutrition environments were most strongly associated with decreases in unhealthy food consumed and stronger intentions to use physical activity resources at church (ps <= .05). Perceived changes in the physical activity environment were unrelated to church or general behavior. Findings suggest that church environments may play an important role in supporting healthy eating and physical activity at church; however, whether the influence of the church environment extends to other settings is unknown. PMID- 26546508 TI - Developing and Implementing "Waupaca Eating Smart": A Restaurant and Supermarket Intervention to Promote Healthy Eating Through Changes in the Food Environment. AB - PURPOSE: Restaurants and food stores are suitable settings for healthy eating interventions. A community-academic partnership developed and implemented "Waupaca Eating Smart" (WES), a healthy eating program in restaurants and supermarkets of a rural, Midwest community. Previous interventions targeted either restaurants or small food stores nearly all in urban areas. Intervention design and implementation is rarely documented, making replication difficult for interested researchers and communities. In this article, we report the activities we undertook to develop and implement WES. METHODS: Working with a local nutrition and activity coalition, we used evidence-based strategies guided by the social ecological model and social marketing principles to inform the content of WES. Formative assessment included a review of the literature, statewide key informant interviews and focus groups with restaurant and food store operators and patrons, a local community survey, and interviews with prospective WES businesses. WES was implemented in seven restaurants and two supermarkets and evaluated for feasibility and acceptance using surveys and direct observation of WES implementation. FINDINGS: Prior to this intervention, only one of seven restaurants had three or more meals that met WES nutrition criteria. By the end of the program, 38 meals were labeled and promoted to restaurant customers, and the team had staffed four side salad taste tests for supermarket customers. Four and 10 months after intervention launch, the majority of the program's strategies were observed in participating outlets, suggesting that these program's strategies are feasible and can be sustained. Operators reported strong satisfaction overall. CONCLUSIONS: A combined restaurant- and supermarket-based healthy eating intervention is feasible and positively valued in rural communities. Further research is needed to better understand how to foster sustainability of these interventions and their impact on customer food choices. PMID- 26546509 TI - A case series of anal melanoma including the results of treatment with imatinib in selected patients. AB - AIM: Anal melanoma is a rare malignancy with a poor prognosis. METHOD: All patients with a diagnosis of anal melanoma treated at a single institution between 2000 and 2012 were identified and their treatment and outcome were evaluated. RESULTS: Sixteen patients had a median survival of 2.9 years. Fourteen had Stage I or II disease with a median survival of 4.0 years and progression free survival of 1.5 years. When used for disease staging, whole body positron emission tomography/CT identified an additional three sites of metastasis in five patients compared with CT of the chest, abdomen and pelvis. Surgery involved wide local excision or abdominoperineal excision with respective local recurrence rates of 50% and 66%. Eleven patients underwent testing for c-Kit mutations, of whom five were positive. Four of these were treated with the tyrosine kinase inhibitor imatinib, and showed rapid response of metastases outside the central nervous system. CONCLUSION: The outcome of this malignancy remains poor. PET is the modality of choice for disease staging. Testing tumours for c-Kit mutations may allow selected patients to participate in trials of tyrosine kinase inhibitors. PMID- 26546510 TI - Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion. AB - Oxaliplatin (OXA) is the common and extremely potent anti-advanced colorectal cancer chemotherapeutic. Accumulating evidence reveals that OXA evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome and dose-limiting adverse effects is poorly understood. It is well known that cyclooxygenase-2 (COX-2) as well as phosphoinositide 3-kinase (PI3K)/Akt signaling mediate the neuropathic pain. But it is still unclear whether COX-2 or PI3K/Akt signaling participates in the regulation of OXA-induced hypersensitivity, as well as the linkage between COX-2 and PI3K/Akt signaling in mediating OXA-induced hypersensitivity. In this paper, we investigated the anti nociceptive effect of celecoxib, an inhibitor of COX-2, on the OXA-induced neuropathic pain. We found that OXA increased the expression of cyclooxygenase-2 (COX-2) and Akt2 in the lumbar 4-5 (L4-5) dorsal root ganglion (DRG). And the administration of celecoxib alleviates the OXA-induced hypersensitivity and suppresses the COX-2 and PI3K/Akt2 signaling. Our findings showed that COX-2 and PI3K/Akt2 signaling in DRG contributed to the OXA-induced neuropathic pain. In addition, celecoxib enhanced the OXA-induced mortality of the human colon cancer cell line HCT-116. Thus, celecoxib might play a dual role in colorectal cancer treatment: alleviating OXA-induced neuropathic pain and facilitating the anti tumor effects of OXA through their synergistic role. PMID- 26546511 TI - Is too much hope placed in egg freezing? PMID- 26546512 TI - A predictive modeling approach for cell line-specific long-range regulatory interactions. PMID- 26546513 TI - Identification of bacterial sRNA regulatory targets using ribosome profiling. AB - Bacteria express large numbers of non-coding, regulatory RNAs known as 'small RNAs' (sRNAs). sRNAs typically regulate expression of multiple target messenger RNAs (mRNAs) through base-pairing interactions. sRNA:mRNA base-pairing often results in altered mRNA stability and/or altered translation initiation. Computational identification of sRNA targets is challenging due to the requirement for only short regions of base-pairing that can accommodate mismatches. Experimental approaches have been applied to identify sRNA targets on a genomic scale, but these focus only on those targets regulated at the level of mRNA stability. Here, we utilize ribosome profiling (Ribo-seq) to experimentally identify regulatory targets of the Escherichia coli sRNA RyhB. We not only validate a majority of known RyhB targets using the Ribo-seq approach, but also discover many novel ones. We further confirm regulation of a selection of known and novel targets using targeted reporter assays. By mutating nucleotides in the mRNA of a newly discovered target, we demonstrate direct regulation of this target by RyhB. Moreover, we show that Ribo-seq distinguishes between mRNAs regulated at the level of RNA stability and those regulated at the level of translation. Thus, Ribo-seq represents a powerful approach for genome-scale identification of sRNA targets. PMID- 26546514 TI - DESM: portal for microbial knowledge exploration systems. AB - Microorganisms produce an enormous variety of chemical compounds. It is of general interest for microbiology and biotechnology researchers to have means to explore information about molecular and genetic basis of functioning of different microorganisms and their ability for bioproduction. To enable such exploration, we compiled 45 topic-specific knowledgebases (KBs) accessible through DESM portal (www.cbrc.kaust.edu.sa/desm). The KBs contain information derived through text mining of PubMed information and complemented by information data-mined from various other resources (e.g. ChEBI, Entrez Gene, GO, KOBAS, KEGG, UniPathways, BioGrid). All PubMed records were indexed using 4,538,278 concepts from 29 dictionaries, with 1 638 986 records utilized in KBs. Concepts used are normalized whenever possible. Most of the KBs focus on a particular type of microbial activity, such as production of biocatalysts or nutraceuticals. Others are focused on specific categories of microorganisms, e.g. streptomyces or cyanobacteria. KBs are all structured in a uniform manner and have a standardized user interface. Information exploration is enabled through various searches. Users can explore statistically most significant concepts or pairs of concepts, generate hypotheses, create interactive networks of associated concepts and export results. We believe DESM will be a useful complement to the existing resources to benefit microbiology and biotechnology research. PMID- 26546515 TI - Legume information system (LegumeInfo.org): a key component of a set of federated data resources for the legume family. AB - Legume Information System (LIS), at http://legumeinfo.org, is a genomic data portal (GDP) for the legume family. LIS provides access to genetic and genomic information for major crop and model legumes. With more than two-dozen domesticated legume species, there are numerous specialists working on particular species, and also numerous GDPs for these species. LIS has been redesigned in the last three years both to better integrate data sets across the crop and model legumes, and to better accommodate specialized GDPs that serve particular legume species. To integrate data sets, LIS provides genome and map viewers, holds synteny mappings among all sequenced legume species and provides a set of gene families to allow traversal among orthologous and paralogous sequences across the legumes. To better accommodate other specialized GDPs, LIS uses open-source GMOD components where possible, and advocates use of common data templates, formats, schemas and interfaces so that data collected by one legume research community are accessible across all legume GDPs, through similar interfaces and using common APIs. This federated model for the legumes is managed as part of the 'Legume Federation' project (accessible via http://legumefederation.org), which can be thought of as an umbrella project encompassing LIS and other legume GDPs. PMID- 26546516 TI - Thermodynamic fingerprints of ligand binding to human telomeric G-quadruplexes. AB - Thermodynamic studies of ligand binding to human telomere (ht) DNA quadruplexes, as a rule, neglect the involvement of various ht-DNA conformations in the binding process. Therefore, the thermodynamic driving forces and the mechanisms of ht-DNA G-quadruplex-ligand recognition remain poorly understood. In this work we characterize thermodynamically and structurally binding of netropsin (Net), dibenzotetraaza[14]annulene derivatives (DP77, DP78), cationic porphyrin (TMPyP4) and two bisquinolinium ligands (Phen-DC3, 360A-Br) to the ht-DNA fragment (Tel22) AGGG(TTAGGG)3 using isothermal titration calorimetry, CD and fluorescence spectroscopy, gel electrophoresis and molecular modeling. By global thermodynamic analysis of experimental data we show that the driving forces characterized by contributions of specific interactions, changes in solvation and conformation differ significantly for binding of ligands with low quadruplex selectivity over duplexes (Net, DP77, DP78, TMPyP4; KTel22 ~ KdsDNA). These contributions are in accordance with the observed structural features (changes) and suggest that upon binding Net, DP77, DP78 and TMPyP4 select hybrid-1 and/or hybrid-2 conformation while Phen-DC3 and 360A-Br induce the transition of hybrid 1 and hybrid-2 to the structure with characteristics of antiparallel or hybrid-3 type conformation. PMID- 26546519 TI - Review: The Prolonged QT Interval: Role of Pro-inflammatory Cytokines, Reactive Oxygen Species and the Ceramide and Sphingosine-1 Phosphate Pathways. AB - Patients with QT prolongation have delayed cardiac repolarization and may suffer fatal ventricular arrhythmias. To determine the role of cytokines in causing this syndrome, we reviewed reports on patients with rheumatoid arthritis, psoriasis and other inflammatory conditions. These patients frequently have prolonged QT, which correlates with increases in tumor necrosis factor alpha, and interleukin 1beta and 6. Studies in experimental models have shown that these cytokines act through stimulation of reactive oxygen species. Our review of data on phospholipidosis and on QT-shortening agents suggests a key role in QT prolongation for the ceramide/sphingosine-1-phosphate rheostat. We conclude that the cause of prolonged QT in inflammatory conditions is cytokine induction of reactive oxygen species and then ceramides, and believe that QT-prolonging agents bypass initial steps of this pathway and directly affect ceramides. Since both pro-inflammatory cytokines and numerous medications cause QT prolongation and ventricular arrhythmias by this mechanism, extra caution is needed when using these agents in patients with inflammatory conditions. PMID- 26546518 TI - The Transporter Classification Database (TCDB): recent advances. AB - The Transporter Classification Database (TCDB; http://www.tcdb.org) is a freely accessible reference database for transport protein research, which provides structural, functional, mechanistic, evolutionary and disease/medical information about transporters from organisms of all types. TCDB is the only transport protein classification database adopted by the International Union of Biochemistry and Molecular Biology (IUBMB). It consists of more than 10,000 non redundant transport systems with more than 11 000 reference citations, classified into over 1000 transporter families. Transporters in TCDB can be single or multi component systems, categorized in a functional/phylogenetic hierarchical system of classes, subclasses, families, subfamilies and transport systems. TCDB also includes updated software designed to analyze the distinctive features of transport proteins, extending its usefulness. Here we present a comprehensive update of the database contents and features and summarize recent discoveries recorded in TCDB. PMID- 26546520 TI - Review: The Role of Insulin-like Growth Factor-1 Signaling Pathways in Uterine Leiomyoma. AB - A growing body of evidence suggests the association of the IGF-I bio-regulatory system with leiomyoma occurrence and growth. The complex interplay between IGF I/IGF-IR and hormonal and other growth factors is, thus, now receiving significant attention. Elucidation of the molecular mechanisms driving the disease may allow for development of novel targeted-therapeutic strategies for the treatment of leiomyomas. Herein, we provide a concise update and overview of the function and regulation of IGF-I and its role in leiomyoma growth. PMID- 26546517 TI - Cross talk of tyrosine kinases with the DNA damage signaling pathways. AB - Tyrosine kinases respond to extracellular and intracellular cues by activating specific cellular signaling cascades to regulate cell cycle, growth, proliferation, differentiation and survival. Likewise, DNA damage response proteins (DDR) activated by DNA lesions or chromatin alterations recruit the DNA repair and cell cycle checkpoint machinery to restore genome integrity and cellular homeostasis. Several new examples have been uncovered in recent studies which reveal novel epigenetic and non-epigenetic mechanisms by which tyrosine kinases interact with DDR proteins to dictate cell fate, i.e. survival or apoptosis, following DNA damage. These studies reveal the ability of tyrosine kinases to directly regulate the activity of DNA repair and cell cycle check point proteins by tyrosine phosphorylation. In addition, tyrosine kinases epigenetically regulate DNA damage signaling pathways by modifying the core histones as well as chromatin modifiers at critical tyrosine residues. Thus, deregulated tyrosine kinase driven epigenomic alterations have profound implications in cancer, aging and genetic disorders. Consequently, targeting oncogenic tyrosine kinase induced epigenetic alterations has gained significant traction in overcoming cancer cell resistance to various therapies. This review discusses mechanisms by which tyrosine kinases interact with DDR pathways to regulate processes critical for maintaining genome integrity as well as clinical strategies for targeted cancer therapies. PMID- 26546521 TI - Effects of Targeted Proton Radiation on Spinal Cord in a Porcine Model: A Pilot Study. AB - AIM: To determine whether proton radiation can be used to treat chronic intractable pain. The focus of this study was on the biological effects of spinal cord irradiation. MATERIALS AND METHODS: Proton radiation (0-25 Gy, single fraction) was applied to the spinal cord within L3-L5 of Yucatan mini-pigs (n=20). Skin reaction, body mass and behavior were monitored. At euthanasia, blood and spinal cord were analyzed. RESULTS: Skin morbidity was mild and overall health for the 5-20 Gy-treated groups was good based on behavior and weight gain up to 8.5-9 months post-exposure. The 25 Gy-treated animals developed hind limb weakness at 2.5-3 months and were euthanized. Radiation had a significant effect on white blood cell count (p<0.05), with the 25 Gy-treated mini-pigs having the highest number of all three major leukocyte populations. A few differences were also noted for erythrocyte parameters, but the blood chemistry panel was normal. Apoptosis in the targeted portion of the spinal cord was elevated in the 20- and 25 Gy-treated groups versus 0 Gy (p<0.05) based on the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. There was a trend (p<0.1) for a radiation effect on glial fibrillary acidic protein expression, with the highest value being found after 25 Gy. Histology showed no difference between 0 versus 25 Gy. CONCLUSION: The data demonstrated that a small segment of the spinal cord can be readily targeted using proton radiation; doses ranging from 5-20 Gy were well tolerated in an animal model with radiosensitivity similar to humans. Future studies with a pain model should use <=15 Gy. PMID- 26546522 TI - Hoechst 33342 Staining Identifies the Progenitor Side Population in NOD.Cg PrkdcscidIL2rgtmWjl/Sz Mice Harboring Pediatric Leukemias. AB - BACKGROUND: A sub-population of stem cells termed side population (SP) has a unique ability for the efflux of Hoechst 33342 dye. Recently, it was hypothesized that efflux properties might facilitate the efflux of accumulated chemotherapeutic drugs and as such constitute a tumor escape mechanism. MATERIALS AND METHODS: As SP characterization in leukemia is incomplete, we characterized SP frequencies in 19 children diagnosed with acute B cell precursor leukemia (BCP ALL), AML and T-ALL and described engraftment properties in immune-compromised NOD.Cg-Prkdc(scid)IL2rg(tmWjl)/Sz (NSG) mice. RESULTS: SP cells are detectable in children and mice irrespective of the origin of the leukemia and flow-cytometric analysis reveals that the SP population is a distinct sub-population. Functionally, the SP size remains stable over serial transplantations indicating that the "stemness" potential of our SP sample cohort was overall low. CONCLUSION: SP cells exist in pediatric leukemia and are maintainable in NSG mice. Thus, our observations may facilitate down-stream characterization of LSCs in future studies. PMID- 26546523 TI - Influence of Palmatine on Bone Metabolism in Ovariectomized Mice and Cytokine Secretion of Osteoblasts. AB - BACKGROUND/AIM: Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), regulate the cognate receptor RANK on osteoclast precursor cells. Herein we examined the inhibitory effects of palmatine on bone metabolism using ovariectomized (OVX) mice. MATERIALS AND METHODS: The first experimentaI set was designed to histologically and biochemically examine mice randomly divided into four groups: sham-operated, OVX, and OVX-palmatine intake groups (1 mg/kg and 10 mg/kg). The second experimental set examined the influence of palmatine on osteoblast-like cells in vitro. RESULTS: Palmatine caused significant suppression of osteoclast numbers in tissues. In palmatine-treated mice, RANKL and OPG expression decreased. In the culture supernatant of MC3T3-E1 cells, RANKL and OPG levels were significantly reduced by palmatine addition. CONCLUSION: Palmatine may attenuate osteoclast differentiation through inhibition of RANKL and OPG expression by osteoblasts. Therefore, palmatine might be a candidate anti-resorptive agent for osteoporosis therapy. PMID- 26546524 TI - Influence of Electroacupuncture Stimulation on Nitric Monoxide Production in Vascular Endothelial Cells in Rats. AB - BACKGROUND/AIM: In Chinese medicine, blood stasis termed as 'Oketsu' means 'preceding state' or 'symptomatic of sickness'. Traditional Chinese medicine may improve blood flow by vasodilation or blood clotting inhibition. Although acupuncture influences the blood circulatory system, its underlying mechanisms remain unclear. Herein we evaluated changes in NO, as reflected by changes in NO2 (-), platelet aggregation, oxidative stress and endocrine responses after acupuncture stimulation in rats. MATERIALS AND METHODS: Acupuncture stimulation was administered to rats randomly divided into five groups: control, N(G)-nitro-L arginine methyl ester hydrochloride (L-NAME) injection, restraint stress (RS), restraint plus acupuncture stimulation (RA), and restraint plus acupuncture with L-NAME (RLA). RESULTS: Compared to those in the RS group, levels of NO2 (-), endothelial nitric oxide synthase (NOS) protein and its mRNA significantly increased and those of hydroperoxide and soluble P-selectin significantly decreased in the RA group. CONCLUSION: Acupuncture stimulation regulates vascular endothelium NOS function and affects vascular resistance and blood characteristics through NO. Additionally, NO produced may modulate excessive reactive oxygen development and blood platelet activation. PMID- 26546525 TI - Suppression of BCL2 by Antisense Oligonucleotides and Compensation by Non Targeted Genes May Enhance Tumor Proliferation. AB - Antisense oligonucleotides have been used to target regulatory proteins in both in vivo and in vitro models of prostate cancer. Our previous studies showed that oligonucleotide-treated LNCaP prostate cancer cells compensate for diminished expression of B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2), an apoptosis inhibitor, by suppressing the expression of caspase-3 (an apoptosis promoter) while enhancing that of serine/threonine protein kinase (AKT1) (another apoptosis inhibitor). In addition, we found an enhanced expression of the androgen receptor (AR), its p300 and interleukin-6 (IL6) co-activators, polymerase transcription mediator (MED12), and growth-regulating signal transducer (STAT3). The net result was an altered pattern of gene expression often associated with more aggressive and proliferative tumors. To further evaluate adaptive compensatory mechanisms related to tumor resistance, aggression and proliferation, herein we evaluated the level of expression of a proliferation antigen (KI-67) and mitosis-regulating cyclins (B1 and D1). Compared to the relative levels of compensation detailed above, we found the expression of KI-67 to be statistically the most enhanced non targeted protein yet identified in compensation for suppression of BCL2. Expression of cyclin D1 was also significantly enhanced, although to a much lesser extent. As a result, we propose that oligonucleotide-mediated treatment could be more effective when directed towards KI-67 and BCL2. This could be accomplished by dual monospecific targeting KI-67 and BCL2, or with a bispecific (or proposed multispecific) oligonucleotide simultaneously targeting both. PMID- 26546526 TI - The Contribution of Interleukin-10 Promoter Genotypes to Susceptibility to Asthma in Adults. AB - AIM: Accumulating evidence suggests that inflammatory processes play a role in asthma etiology, and interleukin-10 (IL10) is an important immunosuppressive cytokine. The present study aimed to evaluate the contribution of IL10 promoter A 1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genetic polymorphisms to the risk of asthma in Taiwan. MATERIALS AND METHODS: Associations of three IL10 polymorphic genotypes with risk of asthma were investigated among 198 patients with asthma and 453 non-asthmatic healthy controls, by polymerase chain reaction-restriction fragment length polymorphism genotyping method. RESULTS: The results showed that the percentages of TT, TC and CC for IL-10 T-819C genotypes were differentially represented at 63.1%, 32.3% and 4.6%, respectively, in the patient group and 53.0%, 36.4% and 10.6%, respectively, in the healthy control group (p for trend=0.0114). The CC genotype carriers were at lower risk for asthma (odds ratio=0.36, 95% confidence interval=0.17-0.76, p=0.0055). There was no difference in the distribution of A-1082G or A-592C genotype between the asthma and non-asthma groups. The protective effects of the CC genotype were obvious among males, but not females, and those aged 25 up to 40 years but not those aged over 40 years. CONCLUSION: The CC genotype of IL10 T-819C compared to the TT genotype may have a protective effect on asthma risk in younger adults (25 40 years old), and males in Taiwan. PMID- 26546527 TI - Radical-scavenging and Anti-inflammatory Activity of Quercetin and Related Compounds and Their Combinations Against RAW264.7 Cells Stimulated with Porphyromonas gingivalis Fimbriae. Relationships between Anti-inflammatory Activity and Quantum Chemical Parameters. AB - BACKGROUND/AIM: The flavonoid quercetin exerts significant anti-inflammatory activity against chronic infections, including periodontal disease. However, it is unclear whether combination of quercetin with other flavonoids enhances antioxidant and anti-inflammatory activity. To clarify the molecular mechanism responsible for the anti-inflammatory activity of quercetin, we investigated the antioxidant, cytotoxicity and anti-inflammatory activity of quercetin and its related compounds, catechin and epicatechin, and their combinations. MATERIALS AND METHODS: Radical-scavenging activities were determined by the 1,1-diphenyl-2 picrylhydrazyl (DPPH) assay, and cytotoxicity against RAW264.7 cells was determined using a cell counting kit (CCK-8). The inhibitory effects of these compounds on the mRNA expression of cyclooxygenase-2 (Cox2), tumor necrosis factor-alpha (Tnfalpha) and nitric oxide synthase 2 (Nos2), in RAW264.7 cells stimulated with Porphyromonas gingivalis (Pg) fimbriae, was also determined using real-time polymerase chain reaction analysis. The phenolic O-H bond dissociation enthalpy (BDE) and quantum chemical parameters were calculated on the basis of density function theory (DFT) BLYP/6-31G*. RESULTS: The DPPH(*) radical scavenging activity (EC50) of quercetin, catechin and epicatechin was 5.5, 7.7 and 6.2 MUM, respectively, whereas the cytotoxicity (LC50) was 4.45, 4.80 and 4.95 mM, respectively. Quercetin had slightly higher cytotoxicity and anti DPPH(*) activity than catechin and epicatechin. The BDE for the three flavonoids at the 4'-OH in the B ring, which is the initial active site, was about 75 kcal/mol. Furthermore, various combinations of quercetin with catechin or epicatechin exerted an antagonistic effect on anti-DPPH(*) activity. Gene expression of Cox2, Tnfalpha and Nos2 stimulated by exposure to Pg-fimbriae was markedly suppressed by quercetin, but was not modulated by its combination with epicatechin. The 50% inhibitory concentration of quercetin for Cox2 expression was approximately 10 MUM, while that of catechin and epicatechin was approximately 500 MUM. Values of the quantum chemical parameters softness (sigma) and electronegativity (chi) were highest for quercetin among the three flavonoids tested. CONCLUSION: The potent anti-inflammatory activity of quercetin appears to be attributable to its high sigma and chi values. Quercetin may be applicable as a preventive agent against inflammatory periodontal disease as a manifestation of systemic disease. PMID- 26546528 TI - Bisdemethoxycurcumin (BDMC) Alters Gene Expression-associated Cell Cycle, Cell Migration and Invasion and Tumor Progression in Human Lung Cancer NCI-H460 Cells. AB - BACKGROUND/AIM: Lung cancer is one of the most common malignancies and a predominant cause of cancer-related death. It can metastasize in almost all organs, and currently, while new cases are increasing, treatment is still insufficient. Bisdemethoxycurcumin (BDMC), one of the components of turmeric, has been known to possess biological activities. However, the effects of BDMC on the genetic level remain unclear. MATERIALS AND METHODS: Human lung cancer NCI-H460 cells were treated with 35 MUM BDMC for 24 h and cells were harvested for total RNA extraction. The purified RNA was used for cDNA synthesis, labeling, microarray hybridization, and flour-labeled cDNA on-chip hybridization. The expression Console software (Affymetrix) with default RNA parameters was used to detect and quantitate concentrations of fluorescent molecules. The key genes involved and their possible interaction pathways were analyzed by the GeneGo software. RESULTS: Seven genes, such as CCNE2 (cyclin E), associated with cell cycle, were over 4-fold overexpressed, 22 genes, such as ERCC6L (excision repair cross-complementing rodent repair deficiency, complementation group 6-like) associated with DNA damage and repair, were from 3- to 4-fold overexpressed and 266, such as cell division cycle, S-phase associated kinase and associated with cell death, genes were from 2- to 3-fold overexpressed. CONCLUSION: BDMC induced changes in gene expression that may reveal cytotoxic information on the genetic level while presenting novel biomarkers or targets for treatment of human lung cancer in the future. PMID- 26546529 TI - Mutagenic Effects of Potassium Dichromate as Evaluated by Means of Animal and Plant Bioindicators. AB - BACKGROUND: Chromium typically occurs in two oxidation states in the natural environment, Cr(3+) [Cr(III)] and Cr(6+) [Cr(VI)]. Out of the two chromium species, Cr(VI) is the most mobile, labile and toxic. Hexavalent chromium [Cr(VI)] compounds are classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents to humans. The main source of release of chromium in aquatic ecosystems is related to the industrial application of this metal in metallurgies, tanneries, and in the manufacturing of paints and dyes. The ecotoxicology of Cr(VI) is linked to its environmental persistence and the ability to induce adverse effects in biological systems. In the present study, we evaluated mutagenic effects of Cr(VI) in animal and plant bioindicators. MATERIALS AND METHODS: We evaluated primary DNA damage and frequencies of micronuclei (MN) and morphological nuclear abnormalities (NA) in erythrocytes in peripheral blood of the fish Oreochromis niloticus exposed to potassium dichromate at 12 mg l(-1). The genotoxicity and cytotoxicity of Cr(VI) in the onion (Allium cepa) test were also assessed. RESULTS: The comet assay showed a significant increase of tailed nucleoids in the erythrocytes of fish treated with K2Cr2O7; MN frequency was also increased in the treatments; cytotoxicity of a low concentration of potassium dichromate, however, was not confirmed. CONCLUSION: The combination of both systems - animal and plant - is adequate and advantageous for mutagenicity evaluation. The findings indicate that at the concentration tested, the chromium compound is a clastogenic as well as an aneugenic. PMID- 26546530 TI - Novel Prognostic Markers Derived from Cardiovascular Magnetic Resonance Imaging in Patients with Stable Chronic Coronary Artery Disease. AB - BACKGROUND: In patients with coronary artery disease (CAD), risk stratification remains a challenge. Recently, epicardial adipose tissue (EAT) assessed by cardiovascular magnetic resonance imaging (CMRI) has emerged as a new marker in patients with CAD. Thus, we aimed to investigate the association of CMR parameters with all-cause and cardiac mortality in patients with CAD. PATIENTS AND METHODS: CMRI examination was performed in 260 patients with CAD. RESULTS: In the 40 patients who died, left ventricular (LV) ejection fraction, right ventricular fractioning shortening, LV remodeling index and indexed EAT were significantly reduced, whereas LV mass index, LV end-diastolic volume index, LV end-systolic volume index, LV end-diastolic diameter and the extent of late gadolinium enhancement expressed as a percentage of the maximum possible score to estimate the extent of LGE relative to LV mass (LGE %), were significantly elevated. Using multivariate analysis, age, LV mass index, extent of LGE % and indexed EAT proved to be independently associated with all-cause and cardiac mortality. CONCLUSION: Age, LV mass index, the extent of LGE % and indexed EAT are independent predictors of mortality that might contribute to a more accurate risk stratification of patients with CAD. PMID- 26546531 TI - Radiation Therapy for Metastatic Spinal Cord Compression in Patients with Hepatocellular Carcinoma. AB - AIM: This is the first study to investigate patients with metastatic spinal cord compression (MSCC) from hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eight patients were analyzed with regard to survival and motor dysfunction. RESULTS: Out of seven factors (age, affected vertebrae, ambulatory status, bone lesions, other distant metastases, time developing motor dysfunction, performance score) ambulatory status (p=0.005) and distant metastases (p=0.032) had a significant influence on survival. Both factors were used as a predictive tool (points: not ambulatory 0, ambulatory 1, distant metastases 0, no distant metastases 1). Total scores were 0, 1 or 2 points. Three-month survival rates were 0%, 67% and 100%, six-month survival rates 0%, 0% and 100%. Progression of motor dysfunction was prevented in 63% of patients; time developing motor deficits showed a trend (p=0.08). CONCLUSION: Many patients with MSCC from HCC have a short survival, which can be predicted with a new tool. Radiation therapy can stop progression of motor dysfunction. PMID- 26546532 TI - Immunosuppression and Abdominal Wall Defects: Use of Autologous Dermis. AB - AIM: The purpose of the present study was to analyze the use of autologous dermis compared to non-biological meshes in repair of abdominal wall defects in patients with redundant skin and immunosuppression. PATIENTS AND METHODS: Eighteen patients with abdominal wall defects, immunosuppression and with redundant skin were divided into two groups: Group A consisted of 11 patients treated with autologous dermis. In these patients, autologous dermis was isolated from the amount of skin resected from the inferior abdominal region that was used as a reinforcement of fascial margins above the defect. Group B consisted of seven patients treated with non-biological meshes We evaluated the infection rate of these groups. RESULTS: The infection rate was significantly lower in group A patients. CONCLUSION: The transplantation of autologous dermis as a reinforcement for the reconstruction of abdominal wall defects is reasonable for highly selected patients. The use of the dermis was proven useful and we found a lower rate of infection and recurrence. PMID- 26546533 TI - Abdominoplasty in Mildly Obese Patients (BMI 30-35 kg/m2): Metabolic, Biochemical and Complication Analysis at One Year. AB - BACKGROUND/AIM: Dermolipectomy dramatically improves the quality of life of previously obese patients. Fat removal in patients undergoing liposuction and reduction mammoplasty has positive effects, but no data regarding sequelae of abdominal dermolipectomy on metabolism have been reported. Thus, the aim of the present study was to assess metabolic and biochemical modifications occurring after abdominoplasty. A correlation between the results and the rate of complications was also evaluated. PATIENTS AND METHODS: One hundred and twenty eight patients with body mass index (BMI) between 30 and 35 kg/m(2) were enrolled. Clinical assessment, anthropometric measurements, blood biochemical analysis (fasting plasma glucose, total cholesterol, free fatty acids, plasma insulin), plasma adipocytokines (leptin, adiponectin,resistin), levels of inflammatory markers [tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL6), C-reactive protein (CRP)] and insulin sensitivity by Homeostasis Model Assessment were performed three times. RESULTS: The average age was 37.6 years. At baseline, the mean (+/-SD) BMI of patients overall was 33.44 (+/-2.3) kg/m(2) and the amount of fat surgically removed was 1,578.33 (+/-1,013.02) g. A significant decrease in BMI at 1 year was found. Adiponectin levels were found to have significantly increased (p<0.05) in long-term evaluation. We noted significant increases in the mean TNFalpha (p<0.05), IL6 (p<0.01) and CRP (p<0.05), with a return to baseline values of all variables. The majority of patients were satisfied with the surgical procedure after 12 months. We noted a lower rate (10%) of complications in patients whose blood analysis showed an increase of adiponectin. CONCLUSION: Abdominal dermolipectomy is a safe surgical procedure that improves the quality of life of previously obese patients from an aesthetic functional view. A statistically significant increase of adiponectin after the procedure was found. A low level of adiponectin after surgery indicates a higher probability of complications. PMID- 26546534 TI - Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis. AB - BACKGROUND/AIM: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. MATERIALS AND METHODS: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. RESULTS: There were marked increases in the CC genotype (94.7% vs 81.8%, p<0.0001) and C allele frequencies (97.0% vs. 90.1%, p<0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found. CONCLUSION: This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population. PMID- 26546536 TI - Errata. PMID- 26546535 TI - Prevalence and Risk Factors for Significant Liver Fibrosis in Patients with HIV Infection. AB - AIM: The aim of the present study was the evaluation of liver fibrosis in a population of patients monoinfected with HIV using the transient liver elastography (FibroScan) method. PATIENTS AND METHODS: A total of 228 consecutive patients with HIV were evaluated: 80 (35.09%) were HIV-1 monoinfected and 148 (64.91%) (HIV)/hepatitis C virus (HCV) co-infected. Echoic liver diagnosis was also performed. RESULTS: F2 Metavir-score fibrosis or higher was found to be associated with drug addiction, alanine aminotransferase >80 UI/l, cluster of differentiation 4 (CD4(+)) T lymphocytes nadir <200 copies/ml, therapy duration, protease inhibitor (PI)-based antiretroviral regimen, HCV infection and AIDS diagnosis. Multivariate analysis highlighted a significant association with drug addiction, AIDS diagnosis, therapy duration and HCV co-infection. Echoic liver diagnosis showed signs of damage among 43.75% of monoinfected patients vs. 62.84% among co-infected. CONCLUSION: Monoinfected patients showed pathological signs both at liver ultrasonography and at FibroScan. In the onset of these changes, a significant role by HIV disease and duration of therapy is observed. PMID- 26546538 TI - Bringing the Teams Together. PMID- 26546539 TI - Impressions from the 2015 ENA General Assembly. PMID- 26546540 TI - 2015 Academy Inductee Reflection: ENA Culture Provides a Foundation for Professional Success. PMID- 26546541 TI - Falls in the Emergency Department. PMID- 26546542 TI - Peripheral Venous Access Catheters Placed in Emergency Care Have a Short Life Expectancy in Intensive Care Units--Voi-Rea Study. PMID- 26546543 TI - Author Response to Potter Letter to the Editor. PMID- 26546544 TI - Comment on "Emergency Nurses' Perceptions of Discharge Processes for Patients Receiving Schedule II and III Medications for Pain Management in the Emergency Department". PMID- 26546545 TI - Response to Coronado Letter. PMID- 26546547 TI - Duration of immune responses after Ebola virus vaccination. PMID- 26546549 TI - Late diagnosis of massive peritoneal hidatidosis after blunt abdominal trauma. PMID- 26546550 TI - Experience with the Nuss technique for the treatment of Pectus Excavatum in Spanish Thoracic Surgery Departments. AB - INTRODUCTION: Although the Nuss technique revolutionized the surgical treatment of pectus excavatum, its use has not become widespread in our country. The aim of this study was to analyze the current use of this technique in a sample of Thoracic Surgery Departments in Spain. METHODS: Observational rectrospective multicentric study analyzing the main epidemiological aspects and clinical results of ten years experience using the Nuss technique. RESULTS: Between 2001 and 2010 a total of 149 patients were operated on (mean age 21.2 years), 74% male. Initial aesthetic results were excellent or good in 93.2%, mild in 4.1% and bad in 2.7%. After initial surgery there were complications in 45 patients (30.6%). The most frequent were wound seroma, bar displacement, stabilizer break, pneumothorax, haemothorax, wound infection, pneumonia, pericarditis and cardiac tamponade that required urgent bar removal. Postoperative pain appeared in all patients. In 3 cases (2%) it was so intense that it required bar removal. After a mean follow-up of 39.2 months, bar removal had been performed in 72 patients (49%), being difficult in 5 cases (7%). After a 1.6 year follow-up period good results persisted in 145 patients (98.7%). CONCLUSION: Nuss technique in adults has had good results in Spanish Thoracic Surgery Departments, however its use has not been generalized. The risk of complications must be taken into account and its indication must be properly evaluated. The possibility of previous conservative treatment is being analyzed in several departments at present. PMID- 26546551 TI - Myelinated mouse nerves studied by X-ray phase contrast zoom tomography. AB - We have used X-ray phase contrast tomography to resolve the structure of uncut, entire myelinated optic, saphenous and sciatic mouse nerves. Intrinsic electron density contrast suffices to identify axonal structures. Specific myelin labeling by an osmium tetroxide stain enables distinction between axon and surrounding myelin sheath. Utilization of spherical wave illumination enables zooming capabilities which enable imaging of entire sciatic internodes as well as identification of sub-structures such as nodes of Ranvier and Schmidt-Lanterman incisures. PMID- 26546548 TI - Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial. AB - BACKGROUND: The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3 EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). METHODS: In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 * 10(10) viral particle units (pu), 2.5 * 10(10) pu, 5 * 10(10) pu, or 1 * 10(11) pu; US participants received 1 * 10(10) pu or 1 * 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 * 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian). FINDINGS: Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 * 10(10) pu, 35 [38%] to 2.5 * 10(10) pu, 35 [38%] to 5 * 10(10) pu, and 11 [12%] to 1 * 10(11) pu) and 20 in the USA (ten [50%] to 1 * 10(10) pu and ten [50%] to 1 * 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 * 10(10) and two [2%] received 1 * 10(11) pu) and four (20%) of 20 in the USA (all received 1 * 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. INTERPRETATION: 1 * 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). FUNDING: Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. PMID- 26546552 TI - Erratum to: Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit's Kidney and Liver: Protection by Ginger (Zingiber officinale). PMID- 26546553 TI - Effects of Selenium-Enriched Probiotics on Lipid Metabolism, Antioxidative Status, Histopathological Lesions, and Related Gene Expression in Mice Fed a High Fat Diet. AB - A total of 80 female albino mice were randomly allotted into five groups (n = 16) as follows: (A) normal control, (B) high-fat diet (HFD),; (C) HFD + probiotics (P), (D) HFD + sodium selenite (SS), and (E) HFD + selenium-enriched probiotics (SP). The selenium content of diets in groups A, B, C, D, and E was 0.05, 0.05, 0.05, 0.3, and 0.3 MUg/g, respectively. The amount of probiotics contained in groups C and E was similar (Lactobacillus acidophilus 0.25 * 10(11)/mL and Saccharomyces cerevisiae 0.25 * 10(9)/mL colony-forming units (CFU)). The high fat diet was composed of 15 % lard, 1 % cholesterol, 0.3 % cholic acid, and 83.7 % basal diet. At the end of the 4-week experiment, blood and liver samples were collected for the measurements of lipid metabolism, antioxidative status, histopathological lesions, and related gene expressions. The result shows that HFD significantly increased the body weights and liver damages compared to control, while P, SS, or SP supplementation attenuated the body weights and liver damages in mice. P, SS, or SP supplementation also significantly reversed the changes of alanine aminotransferase (AST), aspartate aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), total protein (TP), high-density lipoprotein (HDL), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalasa (CAT), and malondialdehyde (MDA) levels induced by HFD. Generally, adding P, SS, or SP up-regulated mRNA expression of carnitine palmitoyltransferase-I (CPT1), carnitine palmitoyltransferase II (CPT2), acetyl-CoA acetyltransferase II (ACAT2), acyl-coenzyme A oxidase (ACOX2), and peroxisome proliferator-activated receptor alpha (PPARalpha) and down regulated mRNA expression of fatty acid synthase (FAS), lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARgamma), and sterol regulatory element-binding protein-1 (SREBP1) involved in lipid metabolism. Among the group, adding SP has a maximum effect in improving lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a HFD. PMID- 26546554 TI - Aluminum Activates PERK-EIF2alpha Signaling and Inflammatory Proteins in Human Neuroblastoma SH-SY5Y Cells. AB - Aluminum is the third most abundant element present in the earth's crust and human exposure to it is possible due to industrialization, utensils, medicines, antiperspirants, etc. Evidences suggest involvement of aluminum in a variety of neurodegenerative disorders including Alzheimer's disease. Endoplasmic reticulum (ER) stress has been implicated in various neurological disorders. ER stress may be a result of impaired calcium homeostasis due to perturbed redox balance and is known to elicit inflammation through the activation of unfolded protein response (UPR). In the present study, we aimed to investigate the role of aluminum in ER stress-mediated activation of inflammatory responses in neuroblastoma cells. Lactate dehydrogenase (LDH) release assay revealed that aluminum compromised the membrane integrity of neuroblastoma cells, probably due to membrane damage, as indicated by enhanced levels of lipid peroxidation (LPO). Besides this, our results clearly demonstrated elevated reactive oxygen species (ROS) levels and a weakened antioxidant defence system manifested by decrease in catalase (CAT) activity and cellular glutathione (GSH). Moreover, we studied the expression of key apoptosis-related proteins, ER stress-mediated activation of UPR, and its downstream inflammatory pathway. It was observed that aluminum potentially enhanced protein levels of PERK, EIF2alpha, caspase 9, caspase 3, and inflammatory markers like NF-kappaB, NLRP3, HMGB1, and nitric oxide (NO). Furthermore, aluminum altered TNFalpha, IL1beta, IL6, and IL10 mRNA levels as well. The overall findings indicated that aluminum mediates UPR activation through ER stress, which results in induction of inflammatory pathway and apoptotic proteins in neuronal cells. PMID- 26546555 TI - Novel interactions of domain III from the envelope glycoprotein of dengue 2 virus with human plasma proteins. AB - Blood cells and plasma are important media for the four serotypes of dengue virus (DENV1-4) spreading into an infected person. Thus, interactions with human plasma proteins are expected to be decisive in the course of the viral infection. Affinity purification followed by MS analysis (AP/MS) was used to isolate and identify plasma-derived proteins capable to interact with a recombinant protein comprising the domain III of the envelope protein of DENV2 (DIIIE2). The elution of the AP potently inhibits DENV2 infection. Twenty-nine proteins were identified using a label-free approach as specifically captured by DIIIE2. Of these, a direct interaction with C reactive protein, thrombin and Inter-alpha-inhibitor complexes was confirmed by ELISA. Results provide further evidence of a significant representation of proteins from complement and coagulation cascades on DENV2 interactome in human plasma and stand out the domain III of the viral envelope protein as participant on these interactions. A functional clustering analysis highlights the presence of three structural motifs among putative DIIIE2 binding proteins: hydroxylation and EGF-like calcium-binding- and Gla domains. BIOLOGICAL SIGNIFICANCE: Early cycles of dengue virus replication take place in human blood cells. Thus, the characterization of the interactome of dengue virus proteins in human plasma can lead to the identification of pivotal interactions for the infection that can eventually constitute the target for the development of methods to control dengue virus-caused disease. In this work we identified 29 proteins from human plasma that potentially interact with the envelope protein of dengue 2 virus either directly or through co-complex formation. C reactive protein, thrombin and Inter-alpha-inhibitor complexes were validated as interactors of the domain III of the envelope protein of dengue 2. Results highlight the presence of three structural motifs among putative DIIIE2-binding proteins: hydroxylation and EGF-like calcium-binding- and Gla domains. This finding together with the participation of domain III of the envelope protein on the interactions with human plasma proteins should contribute to a better understanding of dengue virus interactome in human plasma. Such knowledge can contribute to the development of more effective treatments to infected persons. PMID- 26546556 TI - The phosphoproteome of human Jurkat T cell clones upon costimulation with anti CD3/anti-CD28 antibodies. AB - Phosphorylation is a reversible post-translational modification, playing a vital role in protein function. In T cells, protein phosphorylation is the key mechanism regulating T cell receptor-driven signaling pathways. In order to gain insights into the phosphoproteome evolution of T cell activation, we performed a large-scale quantitative phosphoproteomics study of Jurkat E6.1 (wild type) and Jurkat gamma1 (Phospholipase gamma1 null) cell clones upon costimulation with anti-CD3 and anti-CD28 antibodies at times ranging from 15min to as long as 120min. In total, we identified 5585 phosphopeptides belonging to 2008 phosphoproteins from both cell clones. We detected 130 and 114 novel phosphopeptides in Jurkat E6.1 and Jurkat gamma1 clones, respectively. A significantly lower number of proteins containing regulated phosphorylation sites were identified in Jurkat gamma1 in comparison to Jurkat E6.1, reflecting the vital role of Phospholipase gamma1 in T cell signaling. Several new phosphorylation sites from lymphocyte-specific protein tyrosine kinase (Lck) were identified. Of these, serine-121 showed significant changes in JE6.1 while only small changes in the Jgamma1 clone. Our data may contribute to the current human T cell phosphoproteome and provide a better understanding on T cell receptor signaling. Data are available via ProteomeXchange with identifier PXD002871. PMID- 26546557 TI - Maestro, Marguerite, morphine: The last years in the life of Mikhail Bulgakov. AB - The manuscript pages of the final draft of Master i Margarita, the masterpiece by Mikhail Bulgakov, written in the last four years of his life (1936-1940), have been treated with a mixture of chromatographic beads, namely a strong cation exchanger and a C8 resin. Potential substances captured by the beads, after harvesting them, were eluted with a mixture of isopropyl alcohol, dichloromethane and ammonium hydroxide and the eluate subjected to GC-MS analysis in order to detect the presence, if any, of drugs, due to the fact that the writer suffered intense pains caused by an inherited nephrotic syndrome. Indeed all the pages under investigation (a total of ten, taken at random among 127 foils) contained traces of morphine, from as little as 5 up to 100ng/cm(2). In addition to the intact drug, we could detect one of its metabolites, namely 6-O-acetyl morphine. The significance of these findings in terms of a possible improvement of the novel and in terms of drug use (or abuse) in the modern world is discussed and evaluated. BIOLOGICAL SIGNIFICANCE: The extraction of metabolites/proteins from the surface of the original manuscript pages of Bulgakov masterpiece Master i Margarita has permitted to monitor his health state and intake of medicaments over the last four years of his life. We have ascertained that: (1) he was assuming large doses of morphine as pain killers; (2) he was affected by a nephrotic syndrome, since we could identify three proteins known as biomarkers of this pathology. The double extraction procedure here reported could open up a novel field of investigation of (relatively) ancient manuscripts for metabolome/proteome analysis on the health status of the writer/artist. PMID- 26546558 TI - Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells. AB - Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI. PMID- 26546559 TI - An environmental route of exposure affects the formation of nanoparticle coronas in blood plasma. AB - Nanoparticles (NPs) in contact with biological fluids become covered by a tightly bound layer of proteins, the "protein corona", and it is largely accepted that this corona gives a new identity to NPs in biological milieu. We here consider the exposing scenario of NPs through an environmental route exemplified by the use of hydrophobins, highly adhesive proteins that are secreted into the environment in large quantities by fungi. HFBII of Trichoderma reesei has been used as a model protein and we have shown strong binding to polystyrene NPs of different sizes and surface groups. Hydrophobin coated NPs are shown to strongly increase the stability and the dispersion when exposed to human plasma compared to pristine ones particles. It is also shown that the presence of hydrophobin on the NPs results in an attenuated protein corona formation, in a different corona composition, and we also show that hydrophobin remained strongly associated to the NPs in competition with plasma proteins. As a conclusion we therefore suggest that the route of exposure of nanoparticles strongly affects their surface properties and their possible physiological behavior. SIGNIFICANCE: This work shows how a self-assembling protein, class II hydrophobin HFBII, with interesting biocompatible coating properties, strongly adsorbs on polystyrene NPs. HFBII is also shown to reduce aggregation of the NPs in human plasma which can increase their bioavailability with potential use in biomedical applications. The results here are also of significance for understanding possible interactions of NPs with living organisms. Hydrophobins are secreted in large quantities into the environment by fungi and this work shows how the biological environment of NPs determines the surface and colloidal properties of the particles by forming a protein corona, and that the history of the particle environment, here simulated with hydrophobin exposure, affects both plasma protein corona formation and dispersion behavior. This work thus simulates how alternative exposure routes affect nanoparticle properties, important in understanding the biological fate of NPs. PMID- 26546560 TI - Towards muscle-specific meat color stability of Chinese Luxi yellow cattle: A proteomic insight into post-mortem storage. AB - Searching for potential predictors of meat color is a challenging task for the meat industry. In this study, the relationship between meat color parameters and the sarcoplasmic proteome of M. longissimuss lumborum (LL) and M. psoas major (PM) from Chinese Luxi yellow cattle during post-mortem storage (0, 5, 10 and 15days) were explored with the aid of the integrated proteomics and bioinformatics approaches. Meat color attributes revealed that LL displayed better color stability than PM during storage. Furthermore, sarcoplasmic proteins of these two muscles were compared between days 5, 10, 15 and day 0. Several proteins were closely correlated with meat color attributes and they were muscle specific and responsible for the meat color stability at different storage periods. Glycerol-3-phosphate dehydrogenase, fructose-bisphosphate aldolase A isoform, glycogen phosphorylase, peroxiredoxin-2, phosphoglucomutase-1, superoxide dismutase [Cu-Zn], heat shock cognate protein (71kDa) might serve as the candidate predictors of meat color stability during post-mortem storage. In addition, bioinformatics analyses indicated that more proteins were involved in glycolytic metabolism of LL, which contributed to better meat color stability of LL than PM. The present results could provide a proteomic insight into muscle specific meat color stability of Chinese Luxi yellow cattle during post-mortem storage. PMID- 26546561 TI - You may now kiss the bride: Interpretation of social situations by individuals with right or left hemisphere injury. AB - While left hemisphere damage (LHD) has been clearly shown to cause a range of language impairments, patients with right hemisphere damage (RHD) also exhibit communication deficits, such as difficulties processing prosody, discourse, and social contexts. In the current study, individuals with RHD and LHD were directly compared on their ability to interpret what a character in a cartoon might be saying or thinking, in order to better understand the relative role of the right and left hemisphere in social communication. The cartoon stimuli were manipulated so as to elicit more or less formulaic responses (e.g., a scene of a couple being married by a priest vs. a scene of two people talking, respectively). Participants' responses were scored by blind raters on how appropriately they captured the gist of the social situation, as well as how formulaic and typical their responses were. Results showed that RHD individuals' responses were rated as significantly less appropriate than controls and were also significantly less typical than controls and individuals with LHD. Individuals with RHD produced a numerically lower proportion of formulaic expressions than controls, but this difference was only a trend. Counter to prediction, the pattern of performance across participant groups was not affected by how constrained/formulaic the social situation was. The current findings expand our understanding of the roles that the right and left hemispheres play in social processing and communication and have implications for the potential treatment of social communication deficits in individuals with RHD. PMID- 26546562 TI - Higher education is associated with a better rheumatoid arthritis outcome concerning for pain and function but not disease activity: results from the EIRA cohort and Swedish rheumatology register. AB - INTRODUCTION: Whether low socioeconomic status (SES) is associated with worse rheumatoid arthritis (RA) outcomes in countries with general tax-financed healthcare systems (such as Sweden) remains to be elucidated. Our aim was to investigate the influence of educational background (achieving university/college degree (high) or not (low)) on the outcomes of early RA, in terms of disease activity (DAS28), pain (VAS-pain), and functional impairment (HAQ). METHODS: We evaluated DMARD-naive RA patients recruited in the Epidemiological Investigation of RA (EIRA) study with outcomes followed in the Swedish Rheumatology Quality (SRQ) register (N = 3021). Outcomes were categorized in three ways: (1) scores equal to/above median vs. below median; (2) DAS28-based low disease activity, good response, remission; (3) scores decreased over the median vs. less than median. Associations between educational background and outcomes were calculated by modified Poisson regressions, at diagnosis and at each of the three standard (3, 6, 12 months) follow-up visits. RESULTS: Patients with different educational background had similar symptom durations (195 days) and anti-rheumatic therapies at baseline, and comparable treatment patterns during follow-up. Patients with a high education level had significantly less pain and less functional disability at baseline and throughout the whole follow-up period (VAS-pain: baseline: 49 (28 67) vs. 53 (33-71), p <0.0001; 1-year visit: RR = 0.81 (95% CI 0.73-0.90). HAQ: baseline: 0.88 (0.50-1.38) vs. 1.00 (0.63-1.50), p = 0.001; 1-year visit: 0.84 (0.77-0.92)). They also had greater chances to achieve pain remission (VAS-pain <=20) after one year (1.17 (1.07-1.28)). Adjustments for smoking and BMI altered the results only marginally. Educational background did not influence DAS28-based outcomes. CONCLUSION: In Sweden, with tax-financed, generally accessible healthcare system, RA patients with a high education level experienced less pain and less functional disability. Further, these patients achieved pain remission more often during the first year receiving standard care. Importantly, education background affected neither time to referral to rheumatologists, disease activity nor anti-rheumatic treatments. PMID- 26546563 TI - Choroidal Line Scan Measurements in Swept-Source Optical Coherence Tomography as Surrogates for Volumetric Thickness Assessment. AB - PURPOSE: To compare choroidal thickness of different areas on swept-source optical coherence tomography (SSOCT) line and cube scans for their interchangeable use. DESIGN: Validity analysis. METHODS: SSOCT line and cube scans were obtained from 21 patients with various choroidal thicknesses. Subfoveal center point choroidal thickness, mean central millimeter choroidal thickness, and mean 6-mm-area choroidal thicknesses were obtained from both eyes by 2 independent graders in a reading center setting. Cross-correlations were performed using Passing and Bablok regression models. A 95% confidence interval of slope that included 1 was considered to indicate no significant difference. Average choroidal thickness of center point, Early Treatment Diabetic Retinopathy Study grid subfields, and total grid area of 6 mm on both scans and the correlation between different areas served as main outcome measures. RESULTS: No significant difference between line scans/corresponding subfields of cube scans (outer nasal 0.92-1.11, inner nasal 0.88-1.06, central 0.94-1.11, inner temporal 0.95-1.12, outer temporal 0.93-1.17). No significant difference between subfoveal center point measurement/mean of choroidal thickness in the central millimeter of cube scans (0.89-1.08). Significant difference of subfoveal center point measurement or mean of central millimeter area of cube scans to entire 6-mm area of cube scans (1.01-1.53 and 1.03-1.38). CONCLUSIONS: Measurements on a single SSOCT horizontal line scan can represent the entire choroid but subfoveal center point measurements are only indicative for the central millimeter area. There is a consistent overestimation of choroidal thickness when trying to estimate overall choroidal thickness from any central measurement. PMID- 26546564 TI - Effect of Photorefractive Keratectomy on Nystagmus and Visual Functions in Myopic Patients With Infantile Nystagmus Syndrome. AB - PURPOSE: To determine the effect of photorefractive keratectomy (PRK) on involuntary eye movements, visual acuity, and contrast sensitivity in myopic patients with infantile nystagmus syndrome. DESIGN: Prospective interventional case series. METHODS: This study was conducted on patients with infantile nystagmus syndrome and myopia equal to or more than -1 diopter (D), who were referred to our clinic over a 2-year period. Patients older than 18 years of age with a stable refraction for at least 1 year who were good candidates for PRK were included. Complete ophthalmologic examinations including assessment of best corrected visual acuity (BCVA), contrast sensitivity, and videonystagmography were performed for all patients before and 3 months after surgery. RESULTS: Twenty-four eyes of 12 patients with mean age of 23 +/- 2 years were enrolled in this study. Spherical equivalent refractive error was -2.82 +/- 1.65 D and -0.26 +/- 0.25 D before and after PRK, respectively (P < .001). Monocular BCVA improved from 0.36 +/- 0.21 logMAR to 0.27 +/- 0.25 logMAR and binocular BCVA improved from 0.33 +/- 0.2 logMAR to 0.17 +/- 0.16 logMAR (P < .001). Contrast sensitivity significantly improved at low (P < .001), intermediate (P < .001), and high frequencies (P = .01). The frequency, amplitude, and intensity of nystagmus were significantly decreased after PRK (P < .001). There was no correlation between the degree of myopia correction and improvement in sensory and motor indices of nystagmus (P > .1, Spearman correlation coefficient). CONCLUSION: PRK in patients with infantile nystagmus syndrome and myopia improved monocular and binocular BCVA and contrast sensitivity. Furthermore, motor indices of nystagmus (frequency, amplitude, and intensity) were significantly improved after surgery in these patients. PMID- 26546565 TI - Chemical Potency and Degradation Products of Medications Stored Over 550 Earth Days at the International Space Station. AB - Medications degrade over time, and degradation is hastened by extreme storage conditions. Current procedures ensure that medications aboard the International Space Station (ISS) are restocked before their expiration dates, but resupply may not be possible on future long-duration exploration missions. For this reason, medications stored on the ISS were returned to Earth for analysis. This was an opportunistic, observational pilot-scale investigation to test the hypothesis that ISS-aging does not cause unusual degradation. Nine medications were analyzed for active pharmaceutical ingredient (API) content and degradant amounts; results were compared to 2012 United States Pharmacopeia (USP) requirements. The medications were two sleep aids, two antihistamines/decongestants, three pain relievers, an antidiarrheal, and an alertness medication. Because the samples were obtained opportunistically from unused medical supplies, each medication was available at only 1 time point and no control samples (samples aged for a similar period on Earth) were available. One medication met USP requirements 5 months after its expiration date. Four of the nine (44% of those tested) medications tested met USP requirements 8 months post expiration. Another three medications (33%) met USP guidelines 2-3 months before expiration. One compound, a dietary supplement used as a sleep aid, failed to meet USP requirements at 11 months post expiration. No unusual degradation products were identified. Limited, evidence based extension of medication shelf-lives may be possible and would be useful in preparation for lengthy exploration missions. Only analysis of flight-aged samples compared to appropriately matched ground controls will permit determination of the spaceflight environment on medication stability. PMID- 26546566 TI - Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis. AB - Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis. PMID- 26546567 TI - Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation. AB - We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. PMID- 26546568 TI - Knowledge-based iterative model reconstruction: comparative image quality and radiation dose with a pediatric computed tomography phantom. AB - BACKGROUND: CT of pediatric phantoms can provide useful guidance to the optimization of knowledge-based iterative reconstruction CT. OBJECTIVE: To compare radiation dose and image quality of CT images obtained at different radiation doses reconstructed with knowledge-based iterative reconstruction, hybrid iterative reconstruction and filtered back-projection. MATERIALS AND METHODS: We scanned a 5-year anthropomorphic phantom at seven levels of radiation. We then reconstructed CT data with knowledge-based iterative reconstruction (iterative model reconstruction [IMR] levels 1, 2 and 3; Philips Healthcare, Andover, MA), hybrid iterative reconstruction (iDose(4), levels 3 and 7; Philips Healthcare, Andover, MA) and filtered back-projection. The noise, signal-to-noise ratio and contrast-to-noise ratio were calculated. We evaluated low-contrast resolutions and detectability by low-contrast targets and subjective and objective spatial resolutions by the line pairs and wire. RESULTS: With radiation at 100 peak kVp and 100 mAs (3.64 mSv), the relative doses ranged from 5% (0.19 mSv) to 150% (5.46 mSv). Lower noise and higher signal-to-noise, contrast-to-noise and objective spatial resolution were generally achieved in ascending order of filtered back-projection, iDose(4) levels 3 and 7, and IMR levels 1, 2 and 3, at all radiation dose levels. Compared with filtered back projection at 100% dose, similar noise levels were obtained on IMR level 2 images at 24% dose and iDose(4) level 3 images at 50% dose, respectively. Regarding low contrast resolution, low-contrast detectability and objective spatial resolution, IMR level 2 images at 24% dose showed comparable image quality with filtered back projection at 100% dose. Subjective spatial resolution was not greatly affected by reconstruction algorithm. CONCLUSION: Reduced-dose IMR obtained at 0.92 mSv (24%) showed similar image quality to routine-dose filtered back-projection obtained at 3.64 mSv (100%), and half-dose iDose(4) obtained at 1.81 mSv. PMID- 26546569 TI - Multimodality Evaluation of Intravenous Leiomyomatosis: A Rare, Benign but Potentially Life-Threatening Tumor. AB - BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare tumor, which is usually of uterine origin, characterized by intravascular nodular masses of histologically benign smooth muscle that may extend variable distances, including into the inferior vena cava, right atrium and pulmonary arteries. Tumors may arise from uterine leiomyoma, walls of the uterine vessel, or myometrium. It usually occurs at between 20-70 years of age with a median age of 45 years. The most commonly affected women are pre-menopausal and multiparous. Intra-cardiac extension may represent a diagnostic challenge as it is usually misdiagnosed as a right atrial myxoma and may cause multiple symptoms, such as shortness of breath, tachycardia, chest pain, syncope, and even death. CASE REPORT: We present the case of a 40 year-old female patient with past medical history of arterial hypertension, who was referred to a cardiovascular center due to an intra-cardiac mass found on 2D echocardiogram. The patient was given the rare diagnosis of intravenous leiomyomatosis of the uterus with extension into the gonadal veins, inferior vena cava, right atrium, right ventricle, and main pulmonary arteries. Imaging workup including trans-esophageal echocardiogram, cardiac catheterization, contrast enhanced abdomen and pelvic CT scans, and cardiac MRI was performed for evaluation. CONCLUSIONS: Intravenous leiomyomatosis is a rare diagnosis that merits consideration in a young pre-menopausal female patient with cardiac symptoms associated with a right atrial mass. Radiologists play a vital role in the diagnosis and follow-up of patients with the diagnosis of intravenous leiomyomatosis. Differential diagnosis includes vascular thrombus as well as primary and metastatic tumors. Early detection is imperative for appropriate treatment and surgical planning. PMID- 26546570 TI - Ascaridoid parasites infecting in the frequently consumed marine fishes in the coastal area of China: A preliminary investigation. AB - Marine fishes represent the important components of the diet in the coastal areas of China and they are also natural hosts of various parasites. However, to date, little is known about the occurrence of ascaridoid parasites in the frequently consumed marine fishes in China. In order to determine the presence of ascaridoid parasites in the frequently consumed marine fishes in the coastal town Huizhou, Guangdong Province, China, 211 fish representing 45 species caught from the South China Sea (off Daya Gulf) were examined. Five species of ascaridoid nematodes at different developmental stages were detected in the marine fishes examined herein, including third-stage larva of Anisakis typica (Diesing, 1860), third and fourth-stage larvae of Hysterothylacium sp. IV-A of Shamsi, Gasser & Beveridge, 2013, adult and third-stage larvae of Hysterothylacium zhoushanense Li, Liu & Zhang, 2014, adults and third-stage larvae of Raphidascaris lophii (Wu, 1949) and adults of Raphidascaris longispicula Li, Liu & Zhang, 2012. The overall prevalence of infection is 18.0%. Of them, Hysterothylacium sp. IV-A with the highest prevalence (17.5%) and intensity (mean=14.6) of infection was the predominant species. The prevalence and intensity of A. typica were very low (1/211 of marine fish infected with an intensity of one parasite per fish). The morphological and molecular characterization of all nematode species was provided. A cladistic analysis based on ITS sequence was constructed in order to determine the phylogenetic relationships of these ascaridoid parasites obtained herein. The present study provided important information on the occurrence and diagnosis of ascaridoid nematodes in the commercially important marine fishes from the South China Sea. The low level of infection and the species composition of ascaridoid nematodes seem to indicate the presence of low risk of human anisakidosis when local population consumed these marine fishes examined herein. PMID- 26546571 TI - Atorvastatin and metformin administration modulates experimental Trichinella spiralis infection. AB - The host-parasite interaction can be altered by the changes in the host environment that may be or may not be in favor of successful invasion by the nematode parasite Trichinella spiralis. Metformin and atorvastatin are applied on a wide scale, to the degree that they could be considered as part of the host biochemical environment that can affect the parasite. Therefore, this study aimed to investigate the impact of alteration of the host's biochemical environment by these commonly used drugs upon the course of T. spiralis infection. Mice were divided into three groups: (1) received atorvastatin, (2) received metformin, and (3) untreated, then after one week, animals were infected with T. spiralis. The treatment continued until the end of the experiment. From each group, small intestines and muscles were removed for histopathological, immunohistochemical, and biochemical analyses as well as total muscle larval counts. We found that the oxidative stress and the expression of vascular endothelial growth factor (VEGF) in the muscles were significantly reduced in both drug-receiving groups, while the total larval counts in muscles were only significantly reduced in atorvastatin-receiving group as compared to the infected control group. Moreover, marked reduction in the inflammatory cellular infiltration, cyclooxygenase-2 (COX 2) expression, and oxidative stress was noted in the small intestines of the treated groups as compared to the infected control group. In conclusion, this study provides many insights into the different biochemical changes in the host that the parasite has to face. Moreover, the anti-inflammatory and anti angiogenic effects should be taken into consideration when treating infections in patients on therapy with atorvastatin or metformin. PMID- 26546572 TI - NF-kappaB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI). AB - The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) cell signaling pathway is important in inflammation and cell survival. Inflammation and cell death in the kidney are features of cisplatin-induced AKI. While it is known that cisplatin induces NF-kappaB signaling in the kidney, the NF-kappaB responsive genes and the effect of direct NF-kappaB transcriptional inhibition in cisplatin-induced AKI is not known. Mice injected with cisplatin, 25mg/kg, developed AKI, acute tubular necrosis (ATN) and apoptosis on day 3. Mice were treated with JSH-23 (20 or 40 mg/kg) which directly affects NF-kappaB transcriptional activity. Kidney function, tubular injury (ATN, serum neutrophil gelatinase-associated lipocalin [NGAL], but not apoptosis) and myeloperoxidase (MPO) activity were significantly improved by JSH-23 (40 mg/kg). Sixty one NF kappaB responsive genes were increased by cisplatin of which 21 genes were decreased by JSH-23. Genes that were decreased by JSH-23 that are known to play a role in cisplatin-induced AKI were IL-10, IFN-gamma, chemokine [C-C motif] ligand 2 (CCL2) and caspase-1. Another gene, caspase recruitment domain family, member 11 (CARD11), not previously known to play a role in AKI, was increased more than 20-fold and completely inhibited by JSH-23. CXCL1 and TNF-alpha, known mediators of cisplatin-induced AKI, were decreased by JSH-23. RIPK1 and 3, receptor interacting serine/threonine-protein kinases, that play an important role in necroptosis, were decreased by JSH-23. In mouse proximal tubule cells in culture, JSH-23 resulted in an increase in apoptosis suggesting that the mechanism of protection against AKI by JSH-23 is not due to a direct effect on proximal tubules. In conclusion, NF-kappaB transcriptional inhibition in cisplatin-induced AKI ameliorates kidney function and ATN without a significant effect on apoptosis and is associated with a decrease pro-inflammatory mediators and CARD11. PMID- 26546574 TI - Importance of Implantable Cardioverter-Defibrillator Back-Up in Cardiac Resynchronization Therapy Recipients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: It remains to be determined whether patients receiving cardiac resynchronization therapy (CRT) benefit from the addition of an implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: We performed a literature search looking for studies of patients implanted with CRTs. Comparisons were performed between patients receiving CRT-defibrillator (CRT-D) versus CRT pacemaker (CRT-P). The primary outcome was all-cause mortality. Data were pooled using a random-effects model. The relative risk (RR) and hazard ratio (HR, when available) were used as measurements of treatment effect. Nineteen entries were entitled for inclusion, comprising 12 378 patients (7030 receiving CRT-D and 5348 receiving CRT-P) and 29 799 patient-years of follow-up. Those receiving CRT-D were younger, were more often males, had lower NYHA class, lower prevalence of atrial fibrillation, higher prevalence of ischemic heart disease, and were more often on beta-blockers. Ten studies showed significantly lower mortality rates with the CRT-D device, while the remaining 9 were neutral. The pooled data of studies revealed that CRT-D patients had significantly lower mortality rates compared with CRT-P patients (mortality rates: CRT-D 16.6% versus CRT-P 27.1%; RR=0.69, 95% CI 0.62-0.76; P<0.00001). The number needed to treat to prevent one death was 10. The observed I(2) values showed moderate heterogeneity among studies (I(2)=48%). The benefit of CRT-D was more pronounced in ischemic cardiomyopathy (HR=0.70, 95% CI 0.59-0.83, P<0.001, I(2)=0%), but a trend for benefit, albeit of lower magnitude, could also be seen in non-ischemic dilated cardiomyopathy (HR=0.79, 95% CI 0.61-1.02, P=0.07, I(2)=36%). CONCLUSIONS: The addition of the ICD associates with a reduction in the risk of all-cause mortality in CRT patients. This seems to be more pronounced in patients with ischemic cardiomyopathy. PMID- 26546573 TI - Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia. AB - BACKGROUND: Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury. METHODS AND RESULTS: We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating "carrier" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS. CONCLUSIONS: The protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury. PMID- 26546575 TI - DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats. AB - The transient receptor potential melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity is available. This study characterizes a new TRPM8-selective antagonist (DFL23448 [5-(2-ethyl-2H-tetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol 4-ol]) and evaluates it in cold-induced behavioral tests and tests on bladder function and experimental bladder overactivity in vivo in rats. DFL23448 displayed IC50 values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold, but it had limited activity (IC50 > 10 MUM) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. In rats, DFL23448 administered intravenously or orally had a half-life of 37 minutes or 4.9 hours, respectively. DLF23448 (10 mg/kg i.v.) reduced icilin-induced "wet dog-like" shakes in rats. Intravesical DFL23448 (10 mg/l), but not vehicle, increased micturition intervals, micturition volume, and bladder capacity. During bladder overactivity by intravesical prostaglandin E2 (PGE2), vehicle controls exhibited reductions in micturition intervals, micturition volumes, and bladder capacity by 37%-39%, whereas the same parameters only decreased by 12%-15% (P < 0.05-0.01 versus vehicle) in DFL23448 treated rats. In vehicle-treated rats, but not in DFL23448-treated rats, intravesical PGE2 increased bladder pressures. Intravenous DFL23448 at 10 mg/kg, but not 1 mg/kg DFL23448 or vehicle, increased micturition intervals, micturition volumes, and bladder capacity. During bladder overactivity by intravesical PGE2, micturition intervals, micturition volumes, and bladder capacity decreased in vehicle- and 1 mg/kg DFL23448-treated rats, but not in 10 mg/kg DFL23448-treated rats. Bladder pressures increased less in rats treated with DFL23448 10 mg/kg than in vehicle- or 1 mg/kg DFL23448-treated rats. DFL23448 (10 mg/kg i.v.), but not vehicle, prevented cold stress-induced bladder overactivity. Our results support a role for bladder TRPM8-mediated signals in experimental bladder overactivity. PMID- 26546576 TI - Simulation-Based Cryosurgery Training: Variable Insertion Depth Planning in Prostate Cryosurgery. AB - A proof-of-concept for an advanced-level computerized training tool for cryosurgery is demonstrated, based on three-dimensional cryosurgery simulations and a variable insertion depth strategy for cryoprobes. The objective for system development is two-fold: to identify a cryoprobe layout in order to best match a planning isotherm with the target region shape and to verify that cryoprobe placement does not violate accepted geometric constraints. System validation has been performed by collecting training data from 17 surgical residents having no prior experience or advanced knowledge of cryosurgery. This advanced-level study includes an improved training session design in order to enhance knowledge dissemination and elevate participant motivation to excel. In terms of match between a planning isotherm and the target region shape, results of this demonstrate trainee performance improvement from 4.4% in a pretest to 44.4% in a posttest over a course of 50 minutes of training. In terms of combined performance, including the above-mentioned geometrical match and constraints on cryoprobe placement, this study demonstrates trainee performance improvement from 2.2% in the pretest to 31.1% in the posttest. Given the relatively short training session and the lack of prior knowledge, these improvements are significant and encouraging. These results are of particular significance, as they have been obtained from a surgical resident population which are exposed to the typical stress and constraints in advanced surgical education. PMID- 26546577 TI - Efficacy of various percutaneous interventions for in-stent restenosis: comprehensive network meta-analysis of randomized controlled trials. AB - BACKGROUND: In-stent restenosis (ISR) remains a difficult problem in interventional cardiology. The relative efficacy and safety of available interventions is not clear. We aimed to perform a network meta-analysis using both direct evidence and indirect evidence to compare all available interventions. METHODS AND RESULTS: We systematically searched electronic databases for randomized trials comparing >=2 treatments for ISR. A network meta analysis was performed using a Bayesian approach. Eleven treatments were compared in 31 studies with 8157 patient-years follow-up. Compared with balloon angioplasty, everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13 [0.048-0.35]), paclitaxel-eluting balloon (0.32 [0.20-0.49]), paclitaxel eluting cutting balloon (0.054 [0.0017-0.5]), paclitaxel-eluting stent (0.39 [0.24-0.62]), and sirolimus-eluting stent (0.32 [0.18-0.50]) are associated with lower target vessel revascularization. Balloon angioplasty is not different from cutting balloon (0.73 [0.31-1.5]), excimer laser (0.89 [0.29-2.7]), rotational atherectomy (0.96 [0.53-1.7]), and vascular brachytherapy (0.60 [0.35-1.0]). In drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting stent (0.19 [0.049-0.76]), paclitaxel-eluting balloon (0.43 [0.18-0.80]), paclitaxel-eluting stent (0.35 [0.13-0.76]), and sirolimus-eluting stent (0.36 [0.11-0.86]) for target vessel revascularization. There was no difference between treatments in probable or definitive stent thrombosis. The results of binary restenosis and target lesion revascularization were similar. Paclitaxel-eluting cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have the highest probability of being in the top 3 treatments based on low target lesion revascularization, but there was no statistical significant difference between them. CONCLUSIONS: Balloon angioplasty is inferior to all drug-eluting treatments for ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly everolimus-eluting stent, or paclitaxel-eluting cutting balloon and paclitaxel-eluting balloon should be preferred for treating ISR. PMID- 26546578 TI - Up-regulation of abscisic acid signaling pathway facilitates aphid xylem absorption and osmoregulation under drought stress. AB - The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effects of drought on different feeding stages of pea aphids in the wild-type A17 of Medicago truncatula and ABA signaling pathway mutant sta-1. We examined the impact of drought on plant water status, induced plant defense signaling via the abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) pathways, and on the host nutritional quality in terms of leaf free amino acid content. During the penetration phase of aphid feeding, drought decreased epidermis/mesophyll resistance but increased mesophyll/phloem resistance of A17 but not sta-1 plants. Quantification of transcripts associated with ABA, JA and SA signaling indicated that the drought-induced up-regulation of ABA signaling decreased the SA dependent defense but increased the JA-dependent defense in A17 plants. During the phloem-feeding phase, drought had little effect on the amino acid concentrations and the associated aphid phloem-feeding parameters in both plant genotypes. In the xylem absorption stage, drought decreased xylem absorption time of aphids in both genotypes because of decreased water potential. Nevertheless, the activation of the ABA signaling pathway increased water-use efficiency of A17 plants by decreasing the stomatal aperture and transpiration rate. In contrast, the water potential of sta-1 plants (unable to close stomata) was too low to support xylem absorption activity of aphids; the aphids on sta-1 plants had the highest hemolymph osmolarity and lowest abundance under drought conditions. Taken together this study illustrates the significance of cross-talk between biotic abiotic signaling pathways in plant-aphid interaction, and reveals the mechanisms leading to alter aphid fecundity in water stresses plants. PMID- 26546580 TI - Clinical Outcomes Associated With a Collaborative Pharmacist-Endocrinologist Diabetes Intense Medical Management "Tune Up" Clinic in Complex Patients. AB - BACKGROUND: No previous studies exist examining the impact of a short-term pharmacist-endocrinologist collaborative practice model on glycemic control in complex patients. OBJECTIVE: Evaluate outcomes associated with a PharmD Endocrinologist Diabetes Intense Medical Management (DIMM) "tune up" clinic for complex patients. METHODS: A retrospective cohort study of 99 patients referred to DIMM clinic versus a comparator group of 56 primary care provider (PCP) patients meeting the same criteria (adult type 2 diabetes patients, glycosylated hemoglobin [A1C] >= 8%, follow-up visit within 6 months) in a Veterans Affairs Medical Center. DIMM clinic used a short-term model that coupled personalized clinical care with real-time, patient-specific diabetes education during two to four 60-minute visits over 6 months. PCP patients received usual care. Primary outcome was mean A1C change after 6 months. Secondary measures included fasting blood glucose, lipids, blood pressure, weight, body mass index, and percentage of patients meeting goals. RESULTS: Patients in each group had an average of 8 and were taking 12 to 14 medications daily. Mean A1C (%) improvement in DIMM group was significantly greater at 6 months (-2.4 [SD = 2.1] vs -0.8 [SD = 1.7]; P < 0.001), than PCP group. Percentage meeting A1C goal levels (<7%, <8%, and <9%) was significantly greater at 3 and 6 months compared with baseline in the DIMM group (P < 0.001) versus (only <8%) at 3 and 6 months compared with baseline in PCP group. CONCLUSIONS: The DIMM clinic "tune up" model demonstrates a successful collaborative practice which helped complex diabetes patients achieve glycemic control in a 6-month period. PMID- 26546581 TI - The uncertain future of lay counsellors: continuation of HIV services in Lesotho under pressure. AB - Between 2006 and 2011, when antiretroviral therapy (ART) was scaled up in a context of severe human resources shortages, transferring responsibility for elements in human immunodeficiency virus (HIV) care from conventional health workers to lay counsellors (LCs) contributed to increased uptake of HIV services in Lesotho. HIV tests rose from 79 394 in 2006 to 274 240 in 2011 and, in that same period, the number of people on ART increased from 17 352 to 83 624. However, since 2012, the jobs of LCs have been at risk because of financial and organizational challenges. We studied the role of LCs in HIV care in Lesotho between 2006 and 2013, and discuss potential consequences of losing this cadre. Methods included a case study of LCs in Lesotho based on: (1) review of LC related health policy and planning documents, (2) HIV programme review and (3) workload analysis of LCs. LCs are trained to provide HIV testing and counselling (HTC) and ART adherence support. Funded by international donors, 487 LCs were deployed between 2006 and 2011. However, in 2012, the number of LCs decreased to 165 due to a decreasing donor funds, while administrative and fiscal barriers hampered absorption of LCs into the public health system. That same year, ART coverage decreased from 61% to 51% and facility-based HTC decreased by 15%, from 253 994 in 2011 to 215 042 tests in 2012. The workload analysis indicated that LCs work averagely 77 h per month, bringing considerable relief to the scarce professional health workforce. HIV statistics in Lesotho worsened dramatically in the recent era of reduced support to LCs. This suggests that in order to ensure access to HIV care in an under-resourced setting like Lesotho, a recognized and well-supported counsellor cadre is essential. The continued presence of LCs requires improved prioritization, with national and international support. PMID- 26546582 TI - Relationship between Chinese adjective descriptors of personality and emotional symptoms in young Chinese patients with bipolar disorders. AB - OBJECTIVE: To investigate whether personality traits are related to emotional symptoms (mania, hypomania, and depression) in Chinese patients with bipolar disorders. METHODS: Patients with bipolar I and II disorders, and healthy volunteers, were assessed using the Chinese Adjective Descriptors of Personality (CADP) questionnaire, Mood Disorder Questionnaire (MDQ), Hypomanic Checklist (HCL 32), and Plutchik-van Praag Depression Inventory (PVP). RESULTS: Seventy-three patients with bipolar I disorder, 35 with bipolar II disorder and 216 healthy controls were included. Bipolar I and II groups scored significantly higher on MDQ, HCL-32 and PVP scales than controls; the bipolar II group scored lower on the MDQ, but higher on the HCL-32 and PVP than bipolar I. In the bipolar I group, the CADP Intelligent trait (beta, 0.25) predicted MDQ; Intelligent (beta, -0.24), Agreeable (beta, 0.22) and Emotional (beta, 0.34) traits predicted PVP. In the bipolar II group, Intelligent (beta, 0.22), Agreeable (beta, -0.24) and Unsocial (beta, 0.31) traits predicted MDQ; Intelligent (beta, -0.20), Agreeable (beta, 0.31) and Emotional (beta, -0.26) traits predicted HCL-32. CONCLUSIONS: Four out of five Chinese personality traits were associated with emotional symptoms in patients with bipolar I or II disorder, but displayed different associations depending on disorder type. PMID- 26546583 TI - Fifteen minute consultation: a structured approach to the recognition and management of concussion in children and adolescents. AB - Concussion is a disturbance in brain function caused by a direct or indirect force, which is transmitted to the head. The incidence of concussion is rising, and poor recognition of symptoms, with inappropriate management strategies, increases the risk of long-term cognitive and neuropsychiatric complications. We address some common questions that arise when assessing and managing patients with suspected concussion. PMID- 26546584 TI - Postnatal care: a neonatal perspective (NICE guideline CG 37). PMID- 26546585 TI - Margaret McCartney: is Jeremy Hunt our colleague? PMID- 26546579 TI - Signaling pathways regulating neuron-glia interaction and their implications in Alzheimer's disease. AB - Astrocytes are the most abundant cells in the central nervous system. They play critical roles in neuronal homeostasis through their physical properties and neuron-glia signaling pathways. Astrocytes become reactive in response to neuronal injury and this process, referred to as reactive astrogliosis, is a common feature accompanying neurodegenerative conditions, particularly Alzheimer's disease. Reactive astrogliosis represents a continuum of pathobiological processes and is associated with morphological, functional, and gene expression changes of varying degrees. There has been a substantial growth of knowledge regarding the signaling pathways regulating glial biology and pathophysiology in recent years. Here, we attempt to provide an unbiased review of some of the well-known players, namely calcium, proteoglycan, transforming growth factor beta, NFkappaB, and complement, in mediating neuron-glia interaction under physiological conditions as well as in Alzheimer's disease. This review discusses the role of astrocytic NFkappaB and calcium as well as astroglial secreted factors, including proteoglycans, TGFbeta, and complement in mediating neuronal function and AD pathogenesis through direct interaction with neurons and through cooperation with microglia. PMID- 26546587 TI - Is Free Testosterone Concentration a Prognostic Factor of Survival in Chronic Renal Failure (CRF)? AB - BACKGROUND: Lowered testosterone level in CRF patients is associated with elevated risk of death due to cardiovascular reasons, and is influenced by many factors, including acid-base balance disorders. AIMS: evaluation of testoste-rone concentration (TT) and free testosterone concentration (fT) in pre-dialysis and dialysis patients; assessment of TT and fT relationships with biochemical parameters; evaluation of prognostic importance of TT and fT in predicting patient survival. MATERIAL AND METHODS: 4 groups of men: 14 - on hemodialysis (HD), 13 - on peritoneal dialysis (PD), 9 - with chronic renal failure (CRF) and 8 - healthy (CG), aged 56+/-17, 53+/-15, 68+/-12, 43+/-10 years, respectively. TT and biochemical para-meters were measured; fT was calculated. RESULTS: The lowest TT and fT were observed in HD and CRF, the highest - in CG (p=0.035 for TT; p=0.007 for fT). fT in CRF and CG were different (p=0.031). TT and age was associated in HD (p=0.026). Age and fT was strongly associated in PD (p<0.001). After adjustment for age, TT was negatively associated with BMI (p=0.013) and fT was positively associated with HCO3 level (p=0.007). fT was lower in those who died during 5 years of observation than in survivors (p=0.009). We have found that, opposite to TT, fT appeared to be a better predictor of 5-year survival than age. After combining pH and HCO3 levels into a single variable - no acidosis, acidosis with HCO3 normal serum level, acidosis with low concentrations of HCO3 and adjustment for age and the study group - a trend toward the lowest values of free testosterone in decompensated acidosis was observed (ptrend=0.027). Such a trend was not seen for testosterone concentrations (ptrend=0.107). CONCLUSIONS: Total and free testosterone levels were lower in HD and pre-dialysis than in healthy patients. Free testost-erone level may predict long-term survival better than age. Total and free testosterone levels are lower in metabolic acidosis and total and free testosterone levels were positively associated with HCO3 level. PMID- 26546586 TI - Increased pretreatment serum IFN-beta/alpha ratio predicts non-response to tumour necrosis factor alpha inhibition in rheumatoid arthritis. AB - OBJECTIVE: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. METHODS: We studied sera from a test set of 32 patients with RA from the Auto immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN alpha and IFN-beta activity were measured using a functional reporter cell assay. RESULTS: In the test set, an increased ratio of IFN-beta to IFN-alpha (IFN beta/alpha activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-beta/alpha activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-beta/alpha activity ratio (p=0.005). CONCLUSIONS: Increased pretreatment serum IFN-beta/alpha ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA. PMID- 26546588 TI - Paediatric medial epicondyle fracture without elbow dislocation associated with intra-articular ulnar nerve entrapment. AB - Elbow fractures are not uncommon in children, and some are associated with neurovascular injuries. Having a nerve injury in an elbow fracture without dislocation is rare and was not described in the literature. Here, we have reported probably the first case of an ulnar nerve injury in an elbow fracture without dislocation. A 9-year-old female presented to the emergency department after falling off a monkey bar. She had a painful, swollen and tender right elbow with no history or clinical signs of an elbow dislocation but had complete ulnar nerve palsy. She was managed initially with analgesia and plaster application and was taken directly to the operating theatre. Examination under anaesthesia revealed no elbow joint instability. The ulnar nerve was found entrapped between the trochlea and proximal ulna, intra-articularly. The medial epicondyle was also found avulsed from the humerus, with an incarcerated medial epicondylar fragment in the elbow joint. PMID- 26546589 TI - 2015 AHA Late-Breaking Basic Science Abstracts. PMID- 26546590 TI - Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up regulated miR-422a driving reduction of kallikrein-related peptidase 4. AB - BACKGROUND: Aberrancies in gene expression in immune effector cells and in end organs are implicated in lupus pathogenesis. To gain insights into the mechanisms of tissue injury, we profiled the expression of micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN). METHODS: Kidney specimens were from patients with active proliferative, membranous or mixed LN and unaffected control tissue. Micro-RNAs were quantified by TaqMan Low Density Arrays. Bioinformatics was employed to predict gene targets, gene networks and perturbed signaling pathways. Results were validated by transfection studies (luciferase assay, real time PCR) and in murine LN. Protein expression was determined by immunoblotting and immunohistochemistry. RESULTS: Twenty-four micro-RNAs were dysregulated (9 up regulated, 15 down-regulated) in human LN compared with control renal tissue. Their predicted gene targets participated in pathways associated with TGF-beta, kinases, NF-kappaB, HNF4A, Wnt/beta-catenin, STAT3 and IL-4. miR-422a showed the highest upregulation (17-fold) in active LN and correlated with fibrinoid necrosis lesions (beta = 0.63, P = 0.002). In transfection studies, miR-422a was found to directly target kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was significantly reduced in the kidneys of human and murine LN and correlated inversely with miR-422a levels. Immunohistochemistry confirmed reduced KLK4 protein expression in renal mesangial and tubular epithelial cells in human and murine LN. CONCLUSIONS: KLK4, a serine esterase with putative renoprotective properties, is down-regulated by miR-422a in LN kidney suggesting that, in addition to immune activation, local factors may be implicated in the disease. PMID- 26546591 TI - Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess. AB - BACKGROUND: Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control. METHODS: Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated. RESULTS: Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath. CONCLUSIONS: Reducing BP through the use of a strategy that includes volume control and medication improves symptoms seemingly unrelated to volume excess. In long-term hemodialysis patients, treating hypertension using home BP measurements may improve well-being. PMID- 26546593 TI - E-health in patients with atrial fibrillation. PMID- 26546592 TI - The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation. AB - Background: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. Methods: In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. Results: Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score >=2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). Conclusions: Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks. PMID- 26546594 TI - Who smokes in smoke-free public places in China? Findings from a 21 city survey. AB - Efforts toward controlling secondhand smoke in public places have been made throughout China. However, in contrast to the western world, significant challenges remain for effectively implementing smoke-free regulations. This study explores individual and regional factors which influence smoking in smoke-free public places. Participants included 16 866 urban residents, who were identified through multi-stage sampling conducted in 21 Chinese cities. The reported smoking prevalence in smoke-free public places was 41.2%. Of those who smoked in smoke free public places, 45.9% had been advised to stop smoking. Participants stated that no-smoking warnings/signs with 'please' in the statement had a better likelihood of gaining compliance and preventing smoking in public spaces. Multilevel logistic regression analysis showed that ethnicity, education, occupation, type of smoking, age of smoking initiation, smoking situation, stress, household smoking restrictions and city population were all associated with smoking in smoke-free public places. Interestingly local smoke-free regulations were not associated with smoking in public places. The findings underscore that efforts to restrict smoking in public places in China should emphasize strong enforcement, while simultaneously raising public awareness of the perils of second hand smoke. PMID- 26546595 TI - Exploring the Life Expectancy Increase in Poland in the Context of CVD Mortality Fall: The Risk Assessment Bottom-Up Approach, From Health Outcome to Policies. AB - Life expectancy at birth is considered the best mortality-based summary indicator of the health status of the population and is useful for measuring long-term health changes. The objective of this article was to present the concept of the bottom-up policy risk assessment approach, developed to identify challenges involved in analyzing risk factor reduction policies and in assessing how the related health indicators have changed over time. This article focuses on the reasons of the significant life expectancy prolongation in Poland over the past 2 decades, thus includes policy context. The methodology details a bottom-up risk assessment approach, a chain of relations between the health outcome, risk factors, and health policy, based on Risk Assessment From Policy to Impact Dimension project guidance. A decline in cardiovascular disease mortality was a key factor that followed life expectancy prolongation. Among basic factors, tobacco and alcohol consumption, diet, physical activity, and new treatment technologies were identified. Poor health outcomes of the Polish population at the beginning of 1990s highlighted the need of the implementation of various health promotion programs, legal acts, and more effective public health policies. Evidence-based public health policy needs translating scientific research into policy and practice. The bottom-up case study template can be one of the focal tools in this process. Accountability for the health impact of policies and programs and legitimization of the decisions of policy makers has become one of the key questions nowadays in European countries' decision-making process and in EU public health strategy. PMID- 26546596 TI - Mountain Pine Beetle Host Selection Between Lodgepole and Ponderosa Pines in the Southern Rocky Mountains. AB - Recent evidence of range expansion and host transition by mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) has suggested that MPB may not primarily breed in their natal host, but will switch hosts to an alternate tree species. As MPB populations expanded in lodgepole pine forests in the southern Rocky Mountains, we investigated the potential for movement into adjacent ponderosa pine forests. We conducted field and laboratory experiments to evaluate four aspects of MPB population dynamics and host selection behavior in the two hosts: emergence timing, sex ratios, host choice, and reproductive success. We found that peak MPB emergence from both hosts occurred simultaneously between late July and early August, and the sex ratio of emerging beetles did not differ between hosts. In two direct tests of MPB host selection, we identified a strong preference by MPB for ponderosa versus lodgepole pine. At field sites, we captured naturally emerging beetles from both natal hosts in choice arenas containing logs of both species. In the laboratory, we offered sections of bark and phloem from both species to individual insects in bioassays. In both tests, insects infested ponderosa over lodgepole pine at a ratio of almost 2:1, regardless of natal host species. Reproductive success (offspring/female) was similar in colonized logs of both hosts. Overall, our findings suggest that MPB may exhibit equally high rates of infestation and fecundity in an alternate host under favorable conditions. PMID- 26546597 TI - Does cryostripping add anything to the treatment of the ascending thrombophlebitis of the great saphenous vein? AB - OBJECTIVE: To analyse the differences of outcome between cryostripping and conservative therapy in the treatment of superficial vein thrombosis. PATIENTS AND METHODS: A retrospective analysis was performed between the October of 2001 and the October of 2014. In all, 246 cases were eligible for the study. High ligation, cryostripping and local thrombectomy was carried out on 94 patients with thrombophlebitis of the proximal part of the great saphenous vein. Thromboembolic events, the presence of residual varices and time for recovery were compared to 152 cases treated conservatively because of superficial vein thrombosis. RESULTS: Thromboembolic events were found without significant difference (mean +/- SD for surgery: 1.11 +/- 0.60 and conservative therapy: 1.11 +/- 0.55; p = 0.988) in each group. The presence of residual varices (mean +/- SD for surgery: 1.03 +/- 0.52 and conservative therapy: 1.42 +/- 0.99; p = 0.001) and the time for recovery (mean +/- SD for surgery: 15 +/- 10.50 and conservative therapy: 26 +/- 12.32; p < 0.001) were more favourable in the cryostripping group. CONCLUSION: Our analysis confirmed that cryostripping does not result in a lower risk for thromboembolic complications due to superficial vein thrombosis but can be an alternative method to treat the ascending thrombophlebitis of the great saphenous vein because it has some advantages over conservative treatment on the short term. PMID- 26546598 TI - Development of an ovine model of occlusive arterial injury for the evaluation of endovascular interventions. AB - Endovascular intervention for occlusive arterial trauma is becoming more common in clinical practice. The aim of this study is to present an ovine model of extremity arterial injury for use in future endovascular translational research. Animals under general anesthesia had their left superficial femoral artery exposed, which was bluntly injured over a 2-cm section using a hemostat and injection of air. Occlusion was confirmed on angiography and the flow characteristics measured by ultrasonography. Of five animals enrolled, four occluding lesions were created successfully. Post injury, there was a significant reduction in the median (interquartile range) systolic velocity (cm/sec) on the left (injury) compared to the right (control) side (3.5 (0-16.5) vs. 29 (23.8 43.3); p < 0.001). The ovine superficial femoral artery can be used to consistently produce an occlusive lesion that is suitable for use in the future evaluation of endovascular trauma interventions. PMID- 26546599 TI - Phosphate, pyrophosphate, and vascular calcification: a question of balance. PMID- 26546600 TI - Endovascular reconstruction of unruptured intradural vertebral artery dissecting aneurysms with the Pipeline embolization device. AB - BACKGROUND: Dissecting aneurysms of the vertebral artery (VA) are difficult to treat using current surgical and endovascular techniques. OBJECTIVE: To analyze retrospectively the efficacy and safety of flow diverters in the treatment of dissecting aneurysms of the vertebral artery. METHODS: We identified six patients with six unruptured VA dissecting aneurysms either arising from the V4 or V3-V4 junction that were treated with the Pipeline embolization device (PED) at our institution between July 2012 and February 2015. Among other parameters, technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. RESULTS: PED placement was achieved in all cases and immediate angiography follow-up demonstrated intra aneurysmal contrast stasis with parent artery preservation. A temporary episode of dysarthria was noted in one patient. Major procedure-related complications were not observed. The 6-month follow-up (n=6) demonstrated complete/near complete aneurysm obliteration in five patients and partial obliteration in one. At the 1-year follow-up (n=5) stable complete aneurysm occlusion was seen in two patients. Two cases showed progression from near complete occlusion and partial occlusion at 6 months to complete occlusion and near complete occlusion. One cases showed unchanged near complete occlusion. No aneurysmal bleeding, in-stent stenosis or thromboembolic complication was seen. National Institutes of Health Stroke Scale and modified Rankin scale scores remained unchanged from admission to discharge. CONCLUSIONS: Our preliminary experience with the use of PED for the treatment of intradural VA dissecting aneurysms shows promising short-term results, making this technique a feasible and safe treatment option in patients suitable for this approach. However, long-term and larger cohort studies are needed to validate these results. PMID- 26546601 TI - The Delphi Oracle and the management of aneurysms. PMID- 26546602 TI - Rule of 5: angiographic diameters of cervicocerebral arteries in children and compatibility with adult neurointerventional devices. AB - BACKGROUND AND PURPOSE: The safety of using adult-sized neuroendovascular devices in the smaller pediatric vasculature is not known. In this study we measure vessel diameters in the cervical and cranial circulation in children to characterize when adult-approved devices might be compatible in children. METHODS: For 54 children without vasculopathy (mean age 9.5+/-4.9 years (range 0.02-17.8), 20F/34M) undergoing catheter angiography, the diameters of the large vessels in the cervical and cranial circulation (10 locations, 611 total measurements) were assessed by three radiologists. Mean+/-SD diameter was calculated for the following age groups: 0-6 months, 1, 2, 3, 4, 5-9, 10-14, and 15-18 years. To compare with adult sizes, each vessel measurement was normalized to the respective region mean diameter in the oldest age group (15-18 years). Normalized measurements were compared with age and fitted to a segmented regression. RESULTS: Vessel diameters increased rapidly from 0 to 5 years of age (slope=0.069/year) but changed minimally beyond that (slope=0.005/year) (R(2)=0.2). The regression model calculated that, at 5 years of age, vessels would be 94% of the diameter of the oldest age group (compared with 59% at birth). In addition, most vessels in children under 5, while smaller, were still potentially large enough to be compatible with many adult devices. CONCLUSIONS: The growth curve of the cervicocerebral vasculature displays rapid growth until age 5, at which point most children's vessels are nearly adult size. By age 5, most neuroendovascular devices are size-compatible, including thrombectomy devices for stroke. Under 5 years of age, some devices might still be compatible. PMID- 26546603 TI - The outcomes of digital tip amputation replacement as a composite graft in a paediatric population. AB - Limited studies exist on the outcome of replacing an amputated fingertip as a composite graft. We report the outcomes and predictors for composite graft survival along with the long-term morbidity. A retrospective review of all patients <16 years who underwent composite graft replacement of an amputated fingertip was performed. Long-term morbidity was evaluated through a standardized parental questionnaire. A total of 120 patients were identified, of whom 97 were eligible for inclusion. Parental questionnaires were completed for 42 (43%) patients. There was a 10% complete and 34% partial graft survival rate. Patients aged ?4 were significantly more likely to have complete graft take than those >4. Of the patients, 17% developed post-operative complications; 48% of patients reported a hook-nail deformity and 17% reported cold intolerance. Only 5% of patients reported any functional difficulties long term. The rate of complete composite graft survival in a paediatric population is low, although the long term function of these patients is good. LEVEL OF EVIDENCE: 3. PMID- 26546604 TI - Long-term results of syndactyly correction by the trilobed flap technique focusing on hand function and quality of life. AB - Syndactyly is usually corrected surgically during the first years of life. The trilobed flap, a surgical method that does not require skin grafting, was developed in the 1990s and the short-term results were comparable with previously reported techniques. Here we report on long-term outcomes, focusing on how children perceive their hand function and quality of life when they grow up. A total of 19 patients (29 web spaces) were operated on between 1990 and 2000, and followed-up 16 years later with questionnaires and clinical tests. The patients reported low QuickDASH scores, normal sensibility and dexterity, and minor cold intolerance. Only two reoperations, due to early web creep, were needed. The condition minimally affected the choice of occupations, leisure activities and perceptions of appearance. The trilobed flap technique for release of syndactyly provides a good long-term outcome with good hand function and minimal impact on the quality of life. LEVEL OF EVIDENCE: IV. PMID- 26546605 TI - Clinical and ultrasound features in patients with intersection syndrome or de Quervain's disease. AB - We investigated the demographic characteristics of patients who were diagnosed with intersection syndrome and also investigated the dominance of the affected hand, duration of symptoms and any precipitating factor for pain of the wrist. These features were compared with patients who had de Quervain's disease. Ultrasonography was used to confirm the clinical diagnosis. Intersection syndrome occurred more frequently in men and in the dominant hand than de Quervain's disease when all the patients were compared and when peripartum women were excluded. It occurred at a younger age than de Quervain's disease only when the comparison excluded peripartum women. Patients with intersection syndrome presented with a much shorter duration of symptoms. These results were consistent with previous reports about occupational factors in intersection syndrome, and might be helpful in the understanding of epidemiological difference between the two conditions. LEVEL OF EVIDENCE: Level 3. PMID- 26546606 TI - DNA-PKcs Is Involved in Ig Class Switch Recombination in Human B Cells. AB - Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break repair pathways in mammalian cells and is required for both V(D)J recombination and class switch recombination (CSR), two Ig gene-diversification processes occurring during B cell development. DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) is a component of the classical NHEJ machinery and has a critical function during V(D)J recombination. However, its role in CSR has been controversial. In this study, we examined the pattern of recombination junctions from in vivo-switched B cells from two DNA-PKcs-deficient patients. One of them harbored mutations that did not affect DNA-PKcs kinase activity but caused impaired Artemis activation; the second patient had mutations resulting in diminished DNA-PKcs protein expression and kinase activity. These results were compared with those from DNA-PKcs-deficient mouse B cells. A shift toward the microhomology-based alternative end-joining at the recombination junctions was observed in both human and mouse B cells, suggesting that the classical NHEJ pathway is impaired during CSR when DNA-PKcs is defective. Furthermore, cells from the second patient showed additional or more severe alterations in CSR and/or NHEJ, which may suggest that DNA-PKcs and/or its kinase activity have additional, Artemis-independent functions during these processes. PMID- 26546607 TI - Protection of Insects against Viral Infection by Apoptosis-Dependent Phagocytosis. AB - We investigated whether phagocytosis participates in the protection of insects from viral infection using the natural host-virus interaction between Drosophila melanogaster and Drosophila C virus (DCV). Drosophila S2 cells were induced to undergo apoptotic cell death upon DCV infection. However, UV-inactivated virus was unable to cause apoptosis, indicating the need for productive infection for apoptosis induction. S2 cells became susceptible to phagocytosis by hemocyte derived l(2)mbn cells after viral infection, and the presence of phagocytes in S2 cell cultures reduced viral proliferation. Phagocytosis depended, in part, on caspase activity in S2 cells, as well as the engulfment receptors Draper and integrin betanu in phagocytes. To validate the in vivo situation, adult flies were abdominally infected with DCV, followed by the analysis of fly death and viral growth. DCV infection killed flies in a dose-responding manner, and the activation of effector caspases was evident, as revealed by the cleavage of a target protein ectopically expressed in flies. Furthermore, hemocytes isolated from infected flies contained DCV-infected cells, and preinjection of latex beads to inhibit the phagocytic activity of hemocytes accelerated fly death after viral infection. Likewise, viral virulence was exaggerated in flies lacking the engulfment receptors, and was accompanied by the augmented proliferation of virus. Finally, phagocytosis of DCV-infected cells in vitro was inhibited by phosphatidylserine-containing liposome, and virus-infected flies died early when a phosphatidylserine-binding protein was ectopically expressed. Collectively, our study demonstrates that the apoptosis-dependent, phosphatidylserine-mediated phagocytosis of virus-infected cells plays an important role in innate immune responses against viral infection in Drosophila. PMID- 26546608 TI - Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation. AB - Activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome initiates an inflammatory response, which is associated with host defense against pathogens and the progression of chronic inflammatory diseases such as gout and atherosclerosis. The NLRP3 inflammasome mediates caspase-1 activation and subsequent IL-1beta processing in response to various stimuli, including extracellular ATP, although the roles of intracellular ATP (iATP) in NLRP3 activation remain unclear. In this study, we found that in activated macrophages artificial reduction of iATP by 2 deoxyglucose, a glycolysis inhibitor, caused mitochondrial membrane depolarization, leading to IL-1beta secretion via NLRP3 and caspase-1 activation. Additionally, the NLRP3 activators nigericin and monosodium urate crystals lowered iATP through K(+)- and Ca(2+)-mediated mitochondrial dysfunction, suggesting a feedback loop between iATP loss and lowering of mitochondrial membrane potential. These results demonstrate the fundamental roles of iATP in the maintenance of mitochondrial function and regulation of IL-1beta secretion, and they suggest that maintenance of the intracellular ATP pools could be a strategy for countering NLRP3-mediated inflammation. PMID- 26546609 TI - Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection. AB - Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART. PMID- 26546610 TI - A novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuates acute cellular inflammation in mice. AB - OBJECTIVE AND DESIGN: This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis. MATERIAL/METHODS: LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis. STATISTICAL ANALYSIS: ANOVA (p < 0.05). RESULTS: LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-alpha (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity. CONCLUSION: The novel N-acetyl-D-glucosamine binding lectin isolated from L. araripensis seeds presents anti-inflammatory effect involving the lectin domain and the inhibition of 5-HT, BK, PGE2, NO, TNF alpha and leukocyte rolling and adhesion. PMID- 26546611 TI - Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up. AB - OBJECTIVE: Non-functioning pituitary adenomas (NFAs) have a prevalence of 7 22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors. DESIGN: Retrospective cohort study in a tertiary referral center in the UK. METHODS: A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow up data. RESULTS: Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact. CONCLUSIONS: Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality. PMID- 26546612 TI - Effects of sitagliptin on circulating zinc-alpha2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial. AB - OBJECTIVE: Zinc-alpha2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients. DESIGN AND METHODS: A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations. RESULTS: Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (DeltaZAG) was positively associated with DeltaADI, DeltaHOMA-IR, DeltaBMI, Deltafasting insulin and negatively associated with Delta tumor necrosis factor-alpha (TNF-alpha). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-alpha level (P<0.05). CONCLUSION: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent. PMID- 26546613 TI - Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis. AB - Hundreds of genomic loci have been associated with a significant number of immune mediated diseases, and a large proportion of these associated loci are shared among traits. Both the molecular mechanisms by which these loci confer disease susceptibility and the extent to which shared loci are implicated in a common pathogenesis are unknown. We therefore sought to dissect the functional components at loci shared between two autoimmune diseases: coeliac disease (CeD) and rheumatoid arthritis (RA). We used a cohort of 12 381 CeD cases and 7827 controls, and another cohort of 13 819 RA cases and 12 897 controls, all genotyped with the Immunochip platform. In the joint analysis, we replicated 19 previously identified loci shared by CeD and RA and discovered five new non-HLA loci shared by CeD and RA. Our fine-mapping results indicate that in nine of 24 shared loci the associated variants are distinct in the two diseases. Using cell type-specific histone markers, we observed that loci which pointed to the same variants in both diseases were enriched for marks of promoters active in CD14+ and CD34+ immune cells (P < 0.001), while loci pointing to distinct variants in one of the two diseases showed enrichment for marks of more specialized cell types, like CD4+ regulatory T cells in CeD (P < 0.0001) compared with Th17 and CD15+ in RA (P = 0.0029). PMID- 26546614 TI - 14-3-3 Proteins regulate mutant LRRK2 kinase activity and neurite shortening. AB - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson's disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3theta overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wild-type levels. Similarly, 14-3-3theta overexpression reversed neurite shortening in neuronal cultures from BAC transgenic R1441G-LRRK2 mice. Conversely, inhibition of 14-3-3s by the pan-14-3-3 inhibitor difopein or dominant-negative 14-3-3theta further reduced neurite length in G2019S-LRRK2 cultures. Since G2019S-LRRK2 toxicity is likely mediated through increased kinase activity, we examined 14-3-3theta's effects on LRRK2 kinase activity. 14-3-3theta overexpression reduced the kinase activity of G2019S-LRRK2, while difopein promoted the kinase activity of G2019S-LRRK2. The ability of 14-3-3theta to reduce LRRK2 kinase activity required direct binding of 14-3-3theta with LRRK2. The potentiation of neurite shortening by difopein in G2019S-LRRK2 neurons was reversed by LRRK2 kinase inhibitors. Taken together, we conclude that 14-3-3theta can regulate LRRK2 and reduce the toxicity of mutant LRRK2 through a reduction of kinase activity. PMID- 26546615 TI - Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies. AB - DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points in 1018 mother-child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal characteristics in pregnancy, namely smoking, weight, BMI, selenium and cholesterol level. Offspring of non-drinkers had higher AA on average but this difference appeared to resolve during childhood. The associations between sex, birth weight and AA found in ARIES were replicated in an independent cohort (GOYA). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding of aging. PMID- 26546616 TI - An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib. AB - PURPOSE: To assess the tumor response to the smoothened (SMO) inhibitor, sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) resistant to treatment with vismodegib (GDC0449). EXPERIMENTAL DESIGN: Nine patients with an advanced BCC that was previously resistant to treatment with vismodegib were given sonidegib in this investigational, open-label study. Tumor response was determined using the response evaluation criteria in solid tumors. SMO mutations were identified using biopsy samples from the target BCC location. RESULTS: The median duration of treatment with sonidegib was 6 weeks (range, 3-58 weeks). Five patients experienced progressive disease with sonidegib. Three patients experienced stable disease and discontinued sonidegib either due to adverse events (n = 1) or due to election for surgery (n = 2). The response of one patient was not evaluable. SMO mutations with in vitro data suggesting resistance to Hh pathway inhibition were identified in 5 patients, and none of these patients experienced responses while on sonidegib. CONCLUSIONS: Patients with advanced BCCs that were previously resistant to treatment with vismodegib similarly demonstrated treatment resistance with sonidegib. Patients who have developed treatment resistance to an SMO inhibitor may continue to experience tumor progression in response to other SMO inhibitors. PMID- 26546617 TI - Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors. AB - PURPOSE: The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy. EXPERIMENTAL DESIGN: We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens. RESULTS: PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8(+) T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy. CONCLUSIONS: We show that immunotherapy can be efficiently combined with PDT to eradicate established tumors, based on strong local tumor ablation and the induction of a robust systemic immune response. These results suggest combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced cancer. PMID- 26546618 TI - Combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers. AB - PURPOSE: Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, "aggressive variant prostate cancer (AVPC)" also share molecular features with SCPC. EXPERIMENTAL DESIGN: Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC. RESULTS: Irrespective of morphology, Ki67 and Tp53 stained >=10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples. CONCLUSIONS: Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN. PMID- 26546619 TI - mTOR Inhibitors Suppress Homologous Recombination Repair and Synergize with PARP Inhibitors via Regulating SUV39H1 in BRCA-Proficient Triple-Negative Breast Cancer. AB - PURPOSE: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and has the worst outcome among all subtypes of breast cancers. Although PARP inhibitors represent a promising treatment in TNBC with BRCA1/BRCA2 mutations, there is great interest in identifying drug combinations that can extend the use of PARP inhibitors to a majority of TNBC patients with wild-type BRCA1/BRCA2 Here we explored whether mTOR inhibitors, through modulating homologous recombination (HR) repair, would provide therapeutic benefit in combination with PARP inhibitors in preclinical models of BRCA-proficient TNBC. EXPERIMENTAL DESIGN: We have studied the effects of mTOR inhibitors on HR repair following DNA double strand breaks (DSB). We further demonstrated the in vitro and in vivo activities of combined treatment of mTOR inhibitors with PARP inhibitors in BRCA-proficient TNBC. Moreover, microarray analysis and rescue experiments were used to investigate the molecular mechanisms of action. RESULTS: We found that mTOR inhibitors significantly suppressed HR repair in two BRCA-proficient TNBC cell lines. mTOR inhibitors and PARP inhibitors in combination exhibited strong synergism against these TNBC cell lines. In TNBC xenografts, we observed enhanced efficacy of everolimus in combination with talazoparib (BMN673) compared with either drug alone. We further identified through microarray analysis and by rescue assays that mTOR inhibitors suppressed HR repair and synergized with PARP inhibitors through regulating the expression of SUV39H1 in BRCA-proficient TNBCs. CONCLUSIONS: Collectively, these findings strongly suggest that combining mTOR inhibitors and PARP inhibitors would be an effective therapeutic approach to treat BRCA-proficient TNBC patients. PMID- 26546621 TI - Urgent resection of a giant left atrial appendage aneurysm and mitral valve replacement in a complex case of Hurler-Scheie syndrome. AB - Hurler-Scheie syndrome is a rare lysosomal storage disease affecting the cardiovascular system. Besides the cardiac manifestations, it presents with complications from abnormal proteoglycan deposition in soft tissues in many locations, resulting in joint contractures, paraplegia, impaired vision, airway narrowing and restrictive lung function, to name a few. There are very few reports of surgical management of valvular heart disease due to mucopolysaccharidosis (MPS). We describe the successful management of a patient with an extremely challenging case of mitral valve stenosis and a giant left atrial appendage aneurysm due to MPS type 1 (Hurler-Scheie syndrome). The patient underwent mitral valve replacement and excision of the giant left atrial appendage aneurysm; a similar case has not been previously reported. PMID- 26546620 TI - HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. AB - PURPOSE: Pazopanib is an effective treatment for advanced renal cell carcinoma and soft-tissue sarcoma. Transaminase elevations have been commonly observed in pazopanib-treated patients. We conducted pharmacogenetic analyses to explore mechanistic insight into pazopanib-induced liver injury. EXPERIMENTAL DESIGN: The discovery analysis tested association between four-digit HLA alleles and alanine aminotransferase (ALT) elevation in pazopanib-treated patients with cancer from eight clinical trials (N = 1,188). We conducted confirmatory analysis using an independent dataset of pazopanib-treated patients from 23 additional trials (N = 1,002). Genome-wide association study (GWAS) for transaminase elevations was also conducted. RESULTS: The discovery study identified an association between HLA B*57:01 carriage and ALT elevation [P = 5.0 * 10(-5) for maximum on-treatment ALT (MaxALT); P = 4.8 * 10(-4) for time to ALT > 3* upper limit of normal (ULN) event; P = 4.1 * 10(-5) for time to ALT > 5* ULN event] that is significant after adjustment for number of HLA alleles tested. We confirmed these associations with time to ALT elevation event (P = 8.1 * 10(-4) for ALT > 3* ULN, P = 9.8 * 10(-3) for ALT > 5* ULN) in an independent dataset. In the combined data, HLA-B*57:01 carriage was associated with ALT elevation (P = 4.3 * 10(-5) for MaxALT, P = 5.1 * 10(-6) for time to ALT > 3*ULN event, P = 5.8 * 10(-6) for time to ALT > 5* ULN event). In HLA-B*57:01 carriers and noncarriers, frequency of ALT > 3* ULN was 31% and 19%, respectively, and frequency of ALT > 5* ULN was 18% and 10%, respectively. GWAS revealed a possible borderline association, which requires further evaluation. CONCLUSIONS: These data indicate that HLA-B*57:01 carriage confers higher risk of ALT elevation in patients receiving pazopanib and provide novel insight implicating an immune-mediated mechanism for pazopanib-associated hepatotoxicity in some patients. PMID- 26546622 TI - Combined surgical treatment for severe sleep apnoea, to improve BiPAP compliance. AB - Positive airway pressure (PAP) devices are used in the treatment of obstructive sleep apnoea syndrome (OSAS). In cases of PAP failure, many different surgical methods can be used for the treatment. The authors present an unusual case of a patient with Bi-level PAP (BiPAP)-intolerant severe OSAS who was treated with combined surgical methods. A 55-year-old man was treated with BiPAP due to OSAS; he was admitted to the clinic with nose stuffiness, respiratory distress and BiPAP adherence with tolerance and compliance problems. Septal deviation, concha hypertrophy, lateral pharyngeal band hypertrophy and Thornwaldt cyst were determined in the examination. Combined surgical methods were administered. The patient's apnoea hypopnoea index (AHI) was 72.8 in diagnostic polysomnography. Preoperative AHI was 7.3 and postoperative AHI was 2.3 while using BiPAP and, after the surgery, the BiPAP intolerance was eliminated. The authors suggest that a combination of different surgical methods would be an adjuvant treatment to increase BiPAP compliance. PMID- 26546623 TI - Enterobius vermicularis infection of the liver in a patient with colorectal carcinoma with suspected liver metastasis. AB - A 68-year-old man diagnosed with cT3N2 adenocarcinoma of the rectum presented with a synchronous solitary liver metastasis on CT scan. Neoadjuvant chemoradiotherapy was started to downstage the primary tumour. Resection of the rectal tumour followed 3 months after the last radiotherapy session and primary resection of the isolated liver lesion was performed in the intervening period. Histopathological assessment of the liver lesion, however, showed no malignancy, but did reveal a necrotic infection due to Enterobius vermicularis. This parasite is frequently found in the intestines, but only rarely infects the liver. The patient was subsequently treated with the anthelmintic drug mebendazole 100 mg once a week for 2 weeks. Histopathological assessment of the rectal specimen showed complete regression after neoadjuvant chemoradiotherapy without evidence of remaining E. vermicularis, suggesting pinworm eradication. The patient recovered promptly after both surgical procedures. PMID- 26546624 TI - Chondrosarcoma of the hyoid bone: an atypical site of a sarcoma of the head and the neck. AB - We describe a case of a 73-year-old man with a chondrosarcoma of the hyoid bone. The patient presented with a painless palpable lump in the upper anterior cervical region that had been growing for over 10 months. Fine-needle aspiration cytology suggested pleomorphic adenoma but further imaging investigation with CT revealed an exophytic tumour originating from the body of the hyoid bone with prominent chondroid-like calcifications typical of a chondrosarcoma. Histopathology of the surgical specimen confirmed the diagnosis of a moderately differentiated chondrosarcoma. Chondrosarcomas account for 11% of all bone cancers, of which up to 12% are in the head and neck. Primary sites of the head and the neck include the skull base, the nasal cavity, the maxilla, the mandible and the larynx. Chondrosarcomas of the hyoid bone are exceptionally rare, with only 20 such cases previously reported in the English literature. PMID- 26546625 TI - Thyroid papillary microcarcinoma: an incidental finding in a patient with coronoid hyperplasia. PMID- 26546626 TI - A rare case of metachronous penile and urethral metastases from a rectal mucinous adenocarcinoma. AB - Metastatic lesions in the penis are uncommon in patients with prostate or bladder cancer but penile metastatic lesions from rectal tumours are rare with only 65 cases reported in the literature. We describe the case of a 70-year-old man who developed metastatic lesions within his corpus cavernosum 2 years after being diagnosed and treated for a mucinous adenocarcinoma of the rectum and a year after a wedge resection of an isolated lung metastasis. He proceeded with total penectomy and intraoperatively two skip lesions were also found within the wall of his urethra; histological analysis proved that these were also metastatic lesions. A perineal urethrostomy was formed with the remaining macroscopically healthy urethra. He made a good recovery from his operation and continued his treatment under the oncology team. PMID- 26546627 TI - Think beyond simple pneumonia. PMID- 26546628 TI - Severe ischemic stroke: Too severe for thrombolysis? PMID- 26546629 TI - DTI of tuber and perituberal tissue can predict epileptogenicity in tuberous sclerosis complex. AB - OBJECTIVE: To evaluate whether diffusion tensor imaging (DTI) can predict epileptogenic tubers by measuring apparent diffusion coefficient (ADC), fractional anisotropy, axial diffusivity, and radial diffusivity in both tubers and perituberal tissue in pediatric patients with tuberous sclerosis complex (TSC) undergoing epilepsy surgery. METHODS: We retrospectively selected 23 consecutive patients (aged 0.4-19.6 years, mean age of 5.2; 13 female, 10 male) who underwent presurgical DTI and subsequent surgical resection between 2004 and 2013 from the University of California-Los Angeles TSC Clinic. We evaluated presurgical examinations including video-EEG, brain MRI, (18)F-fluorodeoxyglucose PET, magnetic source imaging, and intraoperative electrocorticography for determining epileptogenic tubers. A total of 545 tubers, 33 epileptogenic and 512 nonepileptogenic, were identified. Two observers generated the regions of interest (ROIs) of tubers (ROI(tuber)), the 4-mm-thick ring-shaped ROIs surrounding the tubers (ROI(perituber)), and the combined ROIs (ROI(tuber+perituber)) in consensus and calculated maximum, minimum, mean, and median values of each DTI measure in each ROI for all tubers. RESULTS: The Mann Whitney U test demonstrated that the epileptogenic group showed higher maximum ADC and radial diffusivity values in all ROIs, and that maximum ADC in ROI(tuber+perituber) showed the strongest difference (p = 0.001). Receiver operating characteristic analysis demonstrated that maximum ADC measurements in ROI(tuber+perituber) (area under curve = 0.68 +/- 0.05, p < 0.001) had 81% sensitivity and 44% specificity for correctly identifying epileptogenic tubers with a cutoff value of 1.32 MUm(2)/ms. CONCLUSIONS: DTI analysis of tubers and perituberal tissue may help to identify epileptogenic tubers in presurgical patients with TSC more easily and effectively than current invasive methods. PMID- 26546630 TI - IV thrombolysis in very severe and severe ischemic stroke: Results from the SITS ISTR Registry. AB - OBJECTIVE: To study the safety of off-label IV thrombolysis in patients with very severe stroke (NIH Stroke Scale [NIHSS] scores >25) compared with severe stroke (NIHSS scores 15-25), where treatment is within European regulations. METHODS: Data were analyzed from 57,247 patients with acute ischemic stroke receiving IV tissue plasminogen activator in 793 hospitals participating in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Registry (2002-2013). Eight hundred sixty-eight patients (1.5%) had NIHSS scores >25 and 19,995 (34.9%) had NIHSS scores 15-25. Outcome measures were parenchymal hemorrhage, symptomatic intracerebral hemorrhage, mortality, and functional outcome. RESULTS: Parenchymal hemorrhage occurred in 10.7% vs 11.0% (p = 0.79), symptomatic intracerebral hemorrhage per SITS-MOST (SITS-Monitoring Study) in 1.4% vs 2.5% (p = 0.052), death at 3 months in 50.4% vs 26.9% (p < 0.001), and functional independence at 3 months in 14.0% vs 29.0% (p < 0.001) of patients with NIHSS scores >25 and NIHSS scores 15-25, respectively. Multivariate adjustment did not change findings from univariate comparisons. Posterior circulation stroke was more common in patients with NIHSS scores >25 (36.2% vs 7.4%, p < 0.001), who were also more often obtunded or comatose on presentation (58.4% vs 7.1%, p < 0.001). Of patients with NIHSS scores >25, 26.2% were treated >3 hours from symptom onset vs 14.5% with NIHSS scores of 15-25. CONCLUSIONS: Our data show no excess risk of cerebral hemorrhage in patients with NIHSS score >25 compared to score 15-25, suggesting that the European contraindication to IV tissue plasminogen activator treatment at NIHSS levels >25 may be unwarranted. Increased mortality and lower rates of functional independence in patients with NIHSS score >25 are explained by higher stroke severity, impaired consciousness on presentation due to posterior circulation ischemia, and longer treatment delays. PMID- 26546631 TI - Small DWI lesions after intracerebral hemorrhage: Are perivascular spaces the missing link? PMID- 26546632 TI - Enlarged perivascular spaces and small diffusion-weighted lesions in intracerebral hemorrhage. AB - OBJECTIVE: To examine the association between enlarged perivascular spaces (EPVS) and the prevalence and extent of small acute diffusion-weighted imaging (DWI) lesions (SA-DWIL) in patients with spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS: We conducted a retrospective review of a consecutive cohort of 201 patients with spontaneous supratentorial ICH who had brain MRI with DWI within 1 month of ICH onset. We compared the clinical and imaging characteristics, including EPVS, of patients with and without SA-DWIL. We used univariate and multivariate logistic regression analyses to determine the variables associated with SA-DWIL. RESULTS: Small acute DWI lesions were detected in 27.9% (n = 56) of patients. Intraventricular and subarachnoid extension of ICH (p <= 0.001), high centrum semiovale (CSO)-EPVS (p < 0.001), high basal ganglia EPVS (p = 0.007), overall extent of white matter hyperintensity (p = 0.018), initial ICH volume (p < 0.001), and mean change in mean arterial blood pressure (delta MAP = MAP at admission - the lowest MAP before MRI scan) (p = 0.027) were associated with SA-DWIL on univariate analyses. On multivariate logistic regression analyses, larger ICH volume (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = 0.006) and high CSO-EPVS (OR 12.56; 95% CI 4.40 35.85; p < 0.001) were independently associated with the presence of SA-DWIL. CONCLUSIONS: In our cohort, high EPVS, in particular CSO-EPVS, and larger hematoma volume emerged as independent predictors for SA-DWIL after ICH. Our findings might provide a new explanation for the pathophysiologic mechanisms predisposing to SA-DWIL after ICH. PMID- 26546633 TI - The Power of Mass Spectroscopy as Arbiter for Immunoassays. PMID- 26546634 TI - Putting Designer Drugs Back in Pandora's Box: Analytical Challenges and Metabolite Identification. PMID- 26546635 TI - Short- and Long-term Biologic Variability of Galectin-3 and Other Cardiac Biomarkers in Patients with Stable Heart Failure and Healthy Adults. AB - BACKGROUND: Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. METHODS: To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3 month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. RESULTS: Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. CONCLUSIONS: The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients. PMID- 26546636 TI - Use of a new generation of adaptive servo ventilation for sleep-disordered breathing in patients with multiple system atrophy. AB - A 70-year-old man (case 1) and a 64-year-old woman (case 2) with multiple system atrophy (MSA) and snoring were admitted for polysomnography. Their awake PaCO2 indicated normocapnia. Apnoea-hypopnoea index (AHI), max transcutaneous carbon dioxide partial pressure (PtcCO2) and DeltaPtcCO2 (max PtcCO2 (during sleep) baseline PtcCO2 (while awake)) were 11.4/h, 63 mm Hg and 18 mm Hg, respectively, in case 1 and 53.1/h, 59 mm Hg and 13 mm Hg, respectively, in case 2. Their sleep disordered breathing (SDB) was diagnosed as obstructive sleep apnoea with hypoventilation. We thought that variable expiratory positive airway pressure and pressure support ventilation (advanced-adaptive servo ventilation (ASV)) might be favourable for their SDB. Polysomnography after introducing advanced-ASV revealed that AHI, max PtcCO2 and DeltaPtcCO2 were 0.2/h, 53 mm Hg and 5 mm Hg, respectively, in case 1 and 1.5/h, 56 mm Hg and 9 mm Hg, respectively, in case 2. Advanced-ASV for treating Cheyne-Stokes breathing may be helpful in SDB in patients with MSA. PMID- 26546638 TI - Farewell and Hail: A Message From the Editor-in-Chief. PMID- 26546637 TI - A direct aspiration first pass technique for retrieval of a detached coil. AB - A 64-year-old man was referred to our hospital for treatment of a cerebral aneurysm that was incidentally found. The aneurysm was 7 mm in size and located on the left anterior communicating artery. Using a balloon assisted technique, we performed coil embolization. During the second coil insertion, the first coil was dislodged into the anterior communicating artery. We attempted coil retrieval using a snare, which was unsuccessful. We applied a direct aspiration first pass technique (ADAPT) and advanced a Penumbra 4MAX immediately proximal to the dislodged coil; the dislodged coil was then successfully retrieved. ADAPT is a simple procedure for retrieval of a detached coil, and it can be used as an alternative to the snare technique. PMID- 26546641 TI - New Tools and Approaches for Family Physicians. AB - This issue of the journal is filled with useful information for practicing family physicians. Several articles introduce new ideas for family physicians to use in the care of their patients, whereas other articles cover new approaches to old problems. Several studies report on procedures performed by family physicians: battlefield acupuncture, colonoscopy, and ultrasound. Some unique alternative care models are described and evaluated. An innovative method of delivering diabetes education seems to work well. Ways to use technology to improve patient care, an update on chronic hepatitis B, and a novel use of social media to understand a rare disease are also included. Readers will come away from this issue with many ideas to consider implementing in their own practices. PMID- 26546642 TI - Family Physicians with a Sports Medicine Certificate of Added Qualification (CAQ): Well Prepared to Meet a Significant Patient Care Need. PMID- 26546643 TI - Family Physicians with a Certificate of Added Qualifications (CAQs) in Sports Medicine Spend the Majority of Their Time Practicing Sports Medicine. AB - While family physicians holding certificates of added qualifications in sports medicine practice in multiple settings, little is currently known about the proportion of their time devoted exclusively to the practice of sports medicine. We found that most spend a majority of their time doing so, and this number has been increasing over the past decade. PMID- 26546644 TI - Ear Acupuncture for Acute Sore Throat: A Randomized Controlled Trial. AB - BACKGROUND: Sore throat is a common cause of pain in outpatient encounters. Battlefield auricular acupuncture (the placing of needles in specific points in the ear) is a modality used to treat acute pain associated with a variety of ailments. The aim of our study was to determine whether auricular acupuncture reduces pain, medication usage, and missed work hours when added to standard therapy in adult patients with acute sore throat. METHODS: We conducted an unblinded, pragmatic, randomized controlled trial among adult, nonpregnant patients presenting to an Air Force family medicine clinic with pain from acute sore throat. A total of 54 patients were followed for 48 hours after treatment. RESULTS: Patients receiving auricular acupuncture reported lower pain scores than those who did not at 15 minutes (6.0 [95% confidence interval (CI), 5.4-6.6] vs 2.6 [95% CI, 1.7-3.5]; P < .0001), 6 hours (4.8 [95% CI, 4.0-5.6] vs 2.5 [95% CI, 1.6-3.4]; P = .0005), and 24 hours (4.1 [95% CI, 3.3-4.9] vs 1.3 [95% CI, 1.0 2.8]; P = .0006). They also reported taking fewer cumulative doses of pain medication at 6 hours (1.07 [95% CI, 0.69-1.45] vs 0.39 [95% CI, 0.2-0.58]; P = .003), 24 hours (2.63 [95% CI, 1.95-3.31] vs 1.37 [95% CI, 0.92-1.82]; P = .004), and 48 hours (4.07 [95% CI, 2.9-5.24] vs 2.19 [95% CI, 1.44-2.94]; P = .009). There was no difference in time missed from work between the auricular acupuncture and standard therapy groups. CONCLUSIONS: Compared with usual treatment, battlefield auricular acupuncture was associated with reduced sore throat pain for 24 hours and decreased use of pain medication for up to 48 hours. There was no apparent effect on hours missed from work. PMID- 26546645 TI - Assessment of Primary Care Physicians' Use of a Pocket Ultrasound Device to Measure Left Ventricular Mass in Patients with Hypertension. AB - PURPOSE: Left ventricular hypertrophy (LVH) is common in primary care and is associated with increased morbidity and mortality. Treatment of underlying hypertension can reverse LVH and eliminate the associated risks. Electrocardiography is widely available and commonly used to screen hypertensive patients for LVH, but it is limited by low sensitivity. Limited echocardiographic measurement of the left ventricle is a method for screening with improved sensitivity; however, it is not currently widely used in the primary care setting. This study attempts to test the accuracy of primary care physicians' (PCPs) measurements of the left ventricle using a pocket-sized ultrasound (pUS) device after a brief training session. METHODS: This study was performed in an outpatient cardiology clinic by 3 family medicine residents and 1 family medicine faculty member after a 4-hour training session. Measurements of the left ventricle were made by PCPs using a pUS device; these measurements were compared with cardiologists' measurements from images obtained by echocardiography technicians. Left ventricular mass index (LVMI) was calculated based on these measurements and then compared between groups. RESULTS: There was no statistically significant difference between the mean LVMI calculations in the 2 groups. The agreement in measurements between the groups, however, showed high variability. This was manifested by the low sensitivity (70%) and specificity (76%) of PCPs in the detection of LVH. CONCLUSIONS: This study showed that limited echocardiography for the detection of LVH performed by PCPs at the point of care was feasible. Future studies are needed to determine the ideal training and experience necessary to yield competency. PMID- 26546646 TI - Expanding Access to Colorectal Cancer Screening: Benchmarking Quality Indicators in a Primary Care Colonoscopy Program. AB - BACKGROUND: An inadequate supply of physicians who perform colonoscopies contributes to suboptimal screening rates, especially among the underserved. This shortage could be reduced if primary care physicians perform colonoscopies. This purpose of this article is to report quality indicators from colonoscopy procedures performed by family medicine physicians as part of a colorectal cancer prevention program targeting uninsured, low-income individuals. METHODS: A grant funded colorectal cancer screening program was implemented to increase access to affordable colonoscopies for underinsured or uninsured residents of target counties while providing colonoscopy training to family medicine resident physicians. Colonoscopies were performed or supervised by 4 board-certified family physicians. Data were collected between 2011 and 2014. RESULTS: A total of 1155 colonoscopies were performed on 1101 individuals over a 3-year period. Cecal intubation rate was 96.25%. Adenoma detection rates among men and women >50 years old were 38.15% and 25.96%, respectively. There was 1 perforation, which was referred to a hospital, and 1 instance of postprocedural bleeding, which spontaneously resolved. CONCLUSIONS: Primary care physicians performing colonoscopies met the recommended quality indicators set forth by the American Society for Gastrointestinal Endoscopy. PMID- 26546647 TI - Connecting Emergency Department Patients to Primary Care. AB - BACKGROUND: Inappropriate emergency department (ED) use among Medicaid enrollees is considered a problem because of cost. We developed and evaluated a system change innovation designed to remove system barriers to primary care access for Medicaid patients. METHODS: Patients who presented to the ED without an identified primary care provider were randomized to the intervention (n = 72) or comparison group (n = 68) for a 12-month study designed to connect these patients to primary care offices. Evaluation was mixed quantitative/qualitative. RESULTS: Significantly more intervention participants attended at least 1 primary care visit 3 months after the intervention (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.06-6.02), though this difference was not significant by 12 months (OR, 1.74; 95% CI, 0.79-3.84). The intervention participants also did not have lower odds of returning to the ED for nonurgent reasons by the 12-month follow-up (OR, 1.27; 95% CI, 0.65-2.48). Patient-reported barriers to attending a primary care appointment were primarily social and health system-related factors. CONCLUSION: The intervention did not decrease ED visits nor increase primary care use over the 12 months of the study period. The qualitative results provide insight into nonurgent ED utilization by patients with Medicaid, suggesting potential future interventions. PMID- 26546648 TI - Primary Care Attributes Associated with Receipt of Preventive Care Services: A National Study. AB - BACKGROUND: Primary care attributes (PCAs) encompassed by patient-centered medical homes may increase receipt of preventive care, though national studies are lacking. METHODS: We performed cross-sectional adjusted analyses of self report data from adults in the 2007 to 2010 US Medical Expenditure Panel Surveys (N = 50,457). PCAs were considered individually and as a total score for each respondent and included comprehensiveness (a usual source of care for new and ongoing problems, preventive care, and referrals); patient-centeredness (shared decision making); and enhanced access (night and weekend hours). Preventive care measures included mammography, influenza vaccination, annual exams, colorectal cancer screening, and Papanicolaou, prostate-specific antigen, and cholesterol testing. RESULTS: The total PCA score was positively associated with increased receipt of each preventive care measure. Colorectal cancer screening (18.5%) and prostate-specific antigen testing (20.7%) showed the largest increases across PCA score quartiles. Individual primary care attributes except enhanced access were positively associated with each preventive care measure. Enhanced access was negatively associated with annual examination (adjusted odds ratio, 0.83; 95% confidence interval, 0.77-0.91). CONCLUSION: In a nationally representative sample, greater reported exposure to key primary care attributes, with the exception of enhanced access, was associated with increased preventive care. These findings may inform best practices for maximizing preventive care delivery. PMID- 26546649 TI - Effect of Physician Participation in a Multi-element Health Information and Data Exchange Program on Chronic Illness Medication Adherence. AB - BACKGROUND: The Primary Care Information Project (PCIP) includes a network of more than 10,000 physicians across New York City focusing on improving the quality of patient care through the use of health information technology and data exchange. METHODS: We assessed adherence, defined as the percentage with a medication possession ratio (MPR) >=80%, across 2 time periods for union members whose primary care providers participated in the PCIP compared with those whose providers did not participate. Using prescription claims data from 2008 and 2011, the MPR was calculated for disease-specific categories of drugs among patients with diabetes, hypertension, and both conditions. RESULTS: Greater improvements in the number of adherent members were observed for the PCIP patients with diabetes who were taking diabetes-specific medications (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.08-3.83 for PCIP, versus OR, 1.14; 95% CI, 0.81 1.60 for non-PCIP) and patients with diabetes who are taking lipid-controlling medications (OR, 1.64; 95% CI, 0.73-3.65 for PCIP versus OR, 0.85; 95% CI, 0.55 1.32 for non-PCIP). However, the magnitude and significance of these associations were diminished when practices providing reduced prescription co-pays were excluded from the analyses. CONCLUSION: Access to primary care providers participating in a public health initiative was associated with some improvement in medication adherence. However, reducing prescription co-pays may be a stronger factor for higher medication adherence among union members. PMID- 26546650 TI - Experiences of Parents Caring for Infants with Rare Scalp Mass as Identified through a Disease-Specific Blog. AB - BACKGROUND: Delayed subaponeurotic fluid collection (DSFC) is a self-limited disorder of unknown etiology characterized by a benign, fluid-filled mass in the subaponeurotic layer of an infant's scalp. While a few case series describe DSFC, the experiences of families whose infants develop this condition have not previously been reported. METHODS: We used a disease-specific blog to evaluate the experiences of 69 families affected by DSFC. We identified self-reported clinical features of DSFC and qualitatively analyzed the families' experiences with obtaining a diagnosis and care for their infants. RESULTS: Infants presented in several clinical settings, and multiple diagnostic procedures were administered, including ultrasound (46%), computed tomography (30%), and head radiography (22%). Qualitative themes emerged: lack of provider awareness of DSFC, concern about potentially harmful diagnostic procedures, suspicion of child abuse, and the importance of the website in providing support to families. CONCLUSIONS: Though DSFC can be diagnosed clinically and its natural history is benign, its presence can be emotionally draining for parents. Physicians should be aware of this clinical entity to rapidly allay parental distress and avoid unnecessary procedures. Disease-specific blogs can help providers learn about rare diseases, contain useful clinical information for research, and can benefit patient care by providing social support for families. PMID- 26546651 TI - Patient Preferences for Receiving Reports of Test Results. AB - INTRODUCTION: The general public's preferences for modes of communication (other than in-person communication) for medical test results were investigated. We hypothesized that patients would prefer a variety of methods to receive common tests results (blood cholesterol and colonoscopy) compared with genetics test results. METHODS: This study was a cross-sectional survey. RESULTS: A total of 409 participants responded to the survey. Among these participants, >=50% reported that they were comfortable receiving results for a blood cholesterol test or colonoscopy via 4 of the 7 non-in-person communication methods (password protected website, personal voicemail, personal E-mail, and letter were preferred over home voicemail, fax, and mobile phone text message). In comparison, >50% of participants were comfortable with only 1 non-in-person communication method for non-HIV sexually transmitted infections (STIs) and none for genetic tests. Patients were least comfortable receiving any information via fax, regardless of test type. There were statistical differences among comfort levels for blood cholesterol and colonoscopy tests and both STIs and genetic testing for personal voicemail, personal E-mail, mobile phone text message, and password-protected website, but there were no differences between STIs and genetic testing. No correlation was found between "familiarity" with test and "comfort" of receiving information about specific test. CONCLUSIONS: Participants demonstrated preferences in how they received test results by non-in-person communication methods, preferring personal E-mail and password-protected websites, but did not prefer fax. Importantly, participants also demonstrated that preference was dependent on test type. PMID- 26546652 TI - Participation in the Journey to Life Conversation Map Improves Control of Hypertension, Diabetes, and Hypercholesterolemia. AB - BACKGROUND: The Diabetes Conversation Map program includes 4 "board game-like" education tools. We describe how the Journey to Life Conversation Map Education Class improves diabetes performance measures of hemoglobin A1c (HbA1c), low density lipoprotein (LDL), and blood pressure (BP). METHODS: Retrospective case control study in a military family medicine clinic from January 2007 to January 2010. We included 202 patients who completed >=1 conversation map class and a comparison group of 209 patients who did not attend. RESULTS: Attendees started with HbA1c 8.25 (95% confidence interval [CI], 7.86-8.64) and decreased to 6.96 (95% CI, 6.69-7.23). Patients in the comparison group started at 8.57 (95% CI, 8.18-8.95) and decreased to 8.27 (95% CI, 8.01-8.54) (P < .001). Attendees began with LDL of 111 mg/dL (95% CI, 103-119) and decreased to 94 mg/dL (95% CI, 81 106). Patients in the comparison group started at 89 mg/dL (95% CI, 81-98) and increased to 98 mg/dL (95% CI, 85-110) (P < .007). Systolic BP decreased 5.4 mmHg among attendees versus 0.8 mmHg among those in the comparison group (P = .014), whereas diastolic BP was unchanged (P = .110). CONCLUSION: The Journey to Life Healthy Interactions Conversation Map Education Class for diabetes improves diabetes performance measures. PMID- 26546653 TI - Intimate Partner Violence and Current Mental Health Needs Among Female Veterans. AB - BACKGROUND: The Veterans Health Administration (VHA) recommends screening female patients for intimate partner violence (IPV), yet few studies inform IPV screening efforts among this population. This study examined the proportion of women who experienced IPV within the past year and the associations between IPV and depression, post-traumatic stress disorder (PTSD), alcohol dependence, mental health multimorbidity (ie, 2 or 3 of these conditions), and military sexual trauma (MST) among female veterans. METHODS: A cross-sectional mail survey of 160 female VHA patients with an intimate partner within the past year was conducted in 2012 in New England. Self-reported IPV was assessed using the Hurt, Insult, Threaten, Scream screening tool. The survey also included validated screening measures of depression (Center for Epidemiologic Studies Depression Scale), PTSD (PTSD Checklist-Civilian), alcohol misuse (10-item Alcohol Use Disorders Identification Test), and MST. RESULTS: Approximately 37% of women reported IPV within the past year on the Hurt, Insult, Threaten, Scream tool. Odds ratios for the associations between reporting IPV and mental health outcomes ranged between 2.75 and 3.67. With the exception of alcohol dependence, IPV remained strongly associated with mental health conditions when adjusting for MST. CONCLUSIONS: These findings can increase provider knowledge of the strong connection between past-year IPV and mental health conditions among female veterans. This may encourage IPV screening and facilitate appropriate referrals, treatment conceptualization, and planning within the VHA and other health care settings. PMID- 26546654 TI - Variations in Metformin Prescribing for Type 2 Diabetes. AB - BACKGROUND: Reasons for suboptimal metformin prescribing are unclear, but may be due to perceived risk of lactic acidosis. The purpose of this study is to describe provider attitudes regarding metformin prescribing in various patient situations. METHODS: An anonymous, electronic survey was distributed electronically to 76 health care providers across the nation. The 14-item survey contained demographic questions and questions related to prescribing of metformin for T2DM in various patient situations, including suboptimal glycemic control, alcohol use, history of lactic acidosis, and varying degrees of severity for certain health conditions, including renal and hepatic dysfunction, chronic obstructive pulmonary disease, and heart failure. RESULTS: There were a total of 100 respondents. For suboptimal glycemic control, most providers (75%) would increase metformin from 1500 to 2000 mg daily; however, 25% would add an alternate agent, such as a sulfonylurea (18%) or dipeptidyl peptidase-4 inhibitor (7%). Although 51% of providers would stop metformin based on serum creatinine thresholds, the remainder would rely on glomerular filtration rate thresholds of <60 mL/min (15%), <30 mL/min (33%), or <15 mL/min (1%) to determine when to stop metformin. For heart failure, 45% of providers would continue metformin as currently prescribed regardless of severity. Most providers would adjust metformin for varying severity of hepatic dysfunction (74%) and alcohol abuse (40%). CONCLUSIONS: Despite evidence supporting the cardiovascular benefits of metformin, provider attitudes toward prescribing metformin are suboptimal in certain patient situations and vary greatly by provider. PMID- 26546655 TI - The Effect of Achieving Patient-Reported Outcome Measures on Satisfaction. AB - OBJECTIVE: To determine how frequently patients with advanced imaging for back or abdominal pain achieve outcomes that are identified by patients as important and whether those achieving those outcomes are more satisfied. METHODS: Cross sectional analysis of survey responses from patients of an 800-physician multi specialty group in Minnesota in 2013. A total of 201 patients with abdominal pain and 167 patients with back pain 1 year earlier that was serious enough for a computed tomography or magnetic resonance imaging scan (67% of those contacted). The main outcomes were the frequency of occurrence of 19 outcomes previously identified by patients as important, plus satisfaction with the results of care. RESULTS: The majority of patients surveyed had achieved most of the desired outcomes. For abdominal pain, 17 of 19 of the desired outcomes were achieved by >50% of patients, while 11 of 19 desired outcomes were achieved by >50% of patients with back pain. Seven of the desired outcomes were significantly associated with satisfaction. CONCLUSION: Achieving outcomes important to patients is associated with greater patient satisfaction. Such measures are potentially valuable measures of quality. PMID- 26546656 TI - Direct Primary Care: Practice Distribution and Cost Across the Nation. AB - Direct primary care (DPC) is an emerging practice alternative that (1) eliminates traditional third-party fee-for-service billing and (2) charges patients a periodic fee for primary care services. We describe the DPC model by identifying DPC practices across the United States; distinguish it from other practice arrangements, such as the "concierge" practice; and describe the model's pricing using data compiled from existing DPC practices across the United States. Lower price points and a broad distribution of DPC practices were confirmed, but data about quality are lacking. PMID- 26546657 TI - Health Considerations in Regulation and Taxation of Electronic Cigarettes. AB - The use of electronic cigarettes (e-cigarettes) is experiencing unprecedented growth. This can be contrasted to the use of conventional cigarettes which showed a decrease among adults with the current smoker prevalence dropping from 20.9% in 2005 to 17.8% in 2013. There is some data that e-cigarettes are attracting both former smokers and never smokers, and in particular, young people as users. Currently most states do not tax e-cigarettes. Taxation and regulation may have a similar overall goal of decreasing smoking but regulation tends to focus reduced availability of products. In terms of tobacco control, taxation focuses on the demand side of the equation. Taxation is a distinct strategy from regulation and has been shown to decrease new adopters of conventional cigarettes. A variety of potential taxation strategies can be considered by policymakers based on different assumptions about e-cigarettes and their utility, ranging from untaxed to taxation at moderate levels compared to conventional cigarettes to taxation equal to conventional cigarettes. Until more evidence for the benefits of e cigarettes is presented, it seems prudent to view them as a potentially harmful and addictive product that ought to be regulated and taxed in an equivalent manner to conventional cigarettes. PMID- 26546658 TI - Out-of-Hours Care Collaboration between General Practitioners and Hospital Emergency Departments in the Netherlands. AB - OBJECTIVE: In the Netherlands, general practitioners (GPs) and emergency departments (EDs) collaborate increasingly in what is called an Urgent Care Collaboration (UCC). In UCCs, GPs and EDs share 1 combined entrance and joint triage. The objective of this study was to determine if GPs treat a larger proportion of out-of-hours patients in the UCC system, and how this relates to patient characteristics. METHODS: This observational study compared patients treated within UCCs with patients treated in the usual care setting, that is, GPs and EDs operating separately. Data on the characteristics of the patients, their consultations, and their health problems were derived from electronic medical records. We performed chi(2) tests, independent sample t tests, and multiple logistic regression analyses. RESULTS: A significantly higher proportion of patients attended their on-call GP within the UCC system. The proportion of ED patients was 22% smaller in UCCs compared to the usual care setting. Controlled for patient and health problem characteristics the difference remained statistically significant (OR=0.69; CI 0.66-0.72) but there were substantial differences between regions. Especially patients with trauma were treated more by general practitioners. Controlled for case mix, patients in the largest UCC region were 1.2 times more likely to attend a GP than the reference group. CONCLUSION: When GPs and EDs collaborate, GPs take a substantially higher proportion of all out-of-hours patients. PMID- 26546659 TI - Association of Older Sister's HPV Vaccination Status on HPV Vaccine Receipt by Adolescents. AB - OBJECTIVE: Efforts to increase human papillomavirus (HPV) vaccine coverage rates in adolescents include finding ways to improve discussions between clinicians and parents. One potentially important piece of information for these discussions is the HPV vaccination status of older siblings. METHODS: A nationally representative online panel was used to conduct a cross-sectional survey of parents of children aged 9 to 17 years in October 2012. RESULTS: Overall, 768 adolescents (35%) had >=1 older sister aged 10 to 26 years. Male and female adolescents with an older sister who had received no HPV vaccine doses demonstrated higher rates of having no doses themselves, compared with those who had no older sister or those who had an older sister who had received >=1 HPV vaccine dose. CONCLUSIONS: Discussing the HPV vaccination status of older sisters may be a useful strategy for providers to differentiate HPV vaccine messages to parents of unvaccinated younger siblings. PMID- 26546660 TI - Optimizing Fracture Prevention in Patients with Osteoporosis. AB - PURPOSE: This Maintenance of Certification activity was designed to help address gaps in osteoporosis management, provide practice improvement based on recognized models, and evaluate the impact of the initiative. METHODS: The program comprised 3 stages: stage A, practice self-assessment and chart review; stage B, an intervention to address at least 1 problem; and stage C, additional chart review (new patients). Data from stages A and C were compared to evaluate the impact of the activity. RESULTS: Of 217 registrants, 62 completed the program, reviewing 2107 and 1814 charts in stages A and C, respectively. Statistically significant improvements occurred in all quality attributes from stage A to stage C in 6 specified domains, except for the proportion of patients with an osteoporosis diagnosis. CONCLUSIONS: Results of this activity support the benefit of performance improvement initiatives and are consistent with other reports. PMID- 26546661 TI - Management of Chronic Hepatitis B: An Overview of Practice Guidelines for Primary Care Providers. AB - Despite the introduction of hepatitis B virus (HBV) vaccination programs, chronic hepatitis B (CHB) remains an important disease burden worldwide and in the United States. A number of clinical practice guidelines are available to assist in the clinical management of CHB by providing recommendations regarding screening and diagnosis, treatment indications, and the choice, duration, and monitoring of treatment. Adherence to these guidelines has proven beneficial in terms of better treatment compliance, improved clinical outcomes, and lower likelihoods of emergency admission. This review summarizes current recommendations from the major clinical CHB practice guidelines and presents a simple algorithm for the treatment of patients with CHB to help primary care providers make informed choices in clinical practice. In general, antiviral treatment should be initiated in patients with CHB who have a high risk of liver-related morbidity and who are likely to respond to treatment, that is, patients with persistently elevated serum HBV DNA and either increased serum alanine aminotransferase concentrations or advanced liver disease. In patients who are eligible for antiviral therapy, treatment should be initiated with one of the recommended first-line therapies (pegylated interferon-alpha, entecavir, or tenofovir), and treatment efficacy should be monitored regularly for serum HBV DNA, alanine aminotransferase, and serologic responses. Patients who are not immediately considered for treatment should be monitored and started on antiviral therapy in case of disease progression. A number of issues in CHB management remain controversial or unresolved, such as identifying treatment candidates, managing partial or nonresponders, and predicting treatment response; we discuss some of the latest evidence around these topics. PMID- 26546662 TI - Cutaneous Sinus Tracts of Odontogenic Origin: Two Case Reports. AB - BACKGROUND: Cutaneous odontogenic fistulas or sinus tracts are frequently misdiagnosed and incorrectly treated, leading to unnecessary procedures and patient suffering. An understanding of the draining of cutaneous sinus tracts will lead to more appropriate treatment. Most cases respond to conservative, nonsurgical root canal therapy. Our objective is to report 2 cases of cutaneous sinus tract secondary to chronic periapical dental infection that were recently observed at our hospital. METHODS: We present 2 cases of recurrent suppurative facial lesions that were initially misdiagnosed and treated with oral antibiotics without response. RESULTS: Clinical findings included palpable facial nodules with drainage, palpable intraoral cords, and poor dentition with gingivitis; radiologic examination showed a periapical disease process consistent with dental sinus tracts. Both of the cases were referred to the maxillofacial department, where the cyst and nonrestorable teeth were extracted. CONCLUSION: Because patients with cutaneous facial sinus tracts of dental origin often do not have obvious dental symptoms, a possible dental etiology may be overlooked. If dental origin is suspected, the diagnosis is easily confirmed by dental examination and dental roentgenograms of the involved area. Early correct diagnosis, based on radiologic evidence of a periapical root infection and treatment of these lesions can help prevent unnecessary and ineffective antibiotic therapy or surgical treatment, reducing the possibility of further complications such as sepsis and osteomyelitis. PMID- 26546663 TI - Where I Practice: On the Spaces of Family Medicine. AB - In this essay, the author explores 3 distinct "spaces" that have helped him metaphorically map the nature of his work as a family physician. These "spaces" represent cultural, personal, and relational environments in which he has practiced over the course of >30 years since beginning medical school. They concern, respectively, the dominant culture of medicine, one core philosophy of family medicine (the biopsychosocialexistential model), and the development of strong therapeutic bonds with patients. The author presents this textual and graphic exploration of "space" in hopes that others might reflect on their work, examine how they approach it, and bring richness and renewed meaning to their work as family physicians. PMID- 26546666 TI - The Adaptor Complex AP-4 Regulates Vacuolar Protein Sorting at the trans-Golgi Network by Interacting with VACUOLAR SORTING RECEPTOR1. AB - Adaptor protein (AP) complexes play critical roles in protein sorting among different post-Golgi pathways by recognizing specific cargo protein motifs. Among the five AP complexes (AP-1-AP-5) in plants, AP-4 is one of the most poorly understood; the AP-4 components, AP-4 cargo motifs, and AP-4 functional mechanism are not known. Here, we identify the AP-4 components and show that the AP-4 complex regulates receptor-mediated vacuolar protein sorting by recognizing VACUOLAR SORTING RECEPTOR1 (VSR1), which was originally identified as a sorting receptor for seed storage proteins to target protein storage vacuoles in Arabidopsis (Arabidopsis thaliana). From the vacuolar sorting mutant library GREEN FLUORESCENT SEED (GFS), we isolated three gfs mutants that accumulate abnormally high levels of VSR1 in seeds and designated them as gfs4, gfs5, and gfs6. Their responsible genes encode three (AP4B, AP4M, and AP4S) of the four subunits of the AP-4 complex, respectively, and an Arabidopsis mutant (ap4e) lacking the fourth subunit, AP4E, also had the same phenotype. Mass spectrometry demonstrated that these four proteins form a complex in vivo. The four mutants showed defects in the vacuolar sorting of the major storage protein 12S globulins, indicating a role for the AP-4 complex in vacuolar protein transport. AP4M bound to the tyrosine-based motif of VSR1. AP4M localized at the trans-Golgi network (TGN) subdomain that is distinct from the AP-1-localized TGN subdomain. This study provides a novel function for the AP-4 complex in VSR1-mediated vacuolar protein sorting at the specialized domain of the TGN. PMID- 26546668 TI - Validating hospital antibiotic purchasing data as a metric of inpatient antibiotic use. AB - OBJECTIVES: Antibiotic purchasing data are a widely used, but unsubstantiated, measure of antibiotic consumption. To validate this source, we compared purchasing data from hospitals and external medical databases with patient-level dispensing data. METHODS: Antibiotic purchasing and dispensing data from internal hospital records and purchasing data from IMS Health were obtained for two hospitals between May 2013 and April 2015. Internal purchasing data were validated against dispensing data, and IMS data were compared with both internal metrics. Scatterplots of individual antimicrobial data points were generated; Pearson's correlation and linear regression coefficients were computed. A secondary analysis re-examined these correlations over shorter calendar periods. RESULTS: Internal purchasing data were strongly correlated with dispensing data, with correlation coefficients of 0.90 (95% CI = 0.83-0.95) and 0.98 (95% CI = 0.95-0.99) at hospitals A and B, respectively. Although dispensing data were consistently lower than purchasing data, this was attributed to a single antibiotic at both hospitals. IMS data were favourably correlated with, but underestimated, internal purchasing and dispensing data. This difference was accounted for by eight antibiotics for which direct sales from some manufacturers were not included in the IMS database. The correlation between purchasing and dispensing data was consistent across periods as short as 3 months, but not at monthly intervals. CONCLUSIONS: Both internal and external antibiotic purchasing data are strongly correlated with dispensing data. If outliers are accounted for appropriately, internal purchasing data could be used for cost-effective evaluation of antimicrobial stewardship programmes, and external data sets could be used for surveillance and research across geographical regions. PMID- 26546667 TI - The EXS Domain of PHO1 Participates in the Response of Shoots to Phosphate Deficiency via a Root-to-Shoot Signal. AB - The response of shoots to phosphate (Pi) deficiency implicates long-distance communication between roots and shoots, but the participating components are poorly understood. We have studied the topology of the Arabidopsis (Arabidopsis thaliana) PHOSPHATE1 (PHO1) Pi exporter and defined the functions of its different domains in Pi homeostasis and signaling. The results indicate that the amino and carboxyl termini of PHO1 are both oriented toward the cytosol and that the protein spans the membrane twice in the EXS domain, resulting in a total of six transmembrane alpha-helices. Using transient expression in Nicotiana benthamiana leaf, we demonstrated that the EXS domain of PHO1 is essential for Pi export activity and proper localization to the Golgi and trans-Golgi network, although the EXS domain by itself cannot mediate Pi export. In contrast, removal of the amino-terminal hydrophilic SPX domain does not affect the Pi export capacity of the truncated PHO1 in N. benthamiana. While the Arabidopsis pho1 mutant has low shoot Pi and shows all the hallmarks associated with Pi deficiency, including poor shoot growth and overexpression of numerous Pi deficiency-responsive genes, expression of only the EXS domain of PHO1 in the roots of the pho1 mutant results in a remarkable improvement of shoot growth despite low shoot Pi. Transcriptomic analysis of pho1 expressing the EXS domain indicates an attenuation of the Pi signaling cascade and the up-regulation of genes involved in cell wall synthesis and the synthesis or response to several phytohormones in leaves as well as an altered expression of genes responsive to abscisic acid in roots. PMID- 26546669 TI - Deep analysis of HIV-1 natural variability across HIV-1 variants at residues associated with integrase inhibitor (INI) resistance in INI-naive individuals. AB - OBJECTIVES: We evaluated variant-associated variability at positions related to resistance to the integrase (IN) inhibitors (INIs) raltegravir, elvitegravir and dolutegravir using HIV-1 IN sequences from naive individuals retrieved from GenBank. METHODS: We evaluated the frequency of major, secondary and rare amino acid changes associated with INI resistance (INI-R) in 6706 sequences from 3791 INI-naive individuals carrying a large panel of different HIV-1 variants retrieved from GenBank, including four groups: M (6663), O (24), N (15) and P (4). HIV-1 group M sequences included 4599 sequences from the nine group M subtypes and 2064 recombinants ascribed to 54 circulating recombinant forms (CRFs). RESULTS: Primary INI-R mutations were rare in INI-naive participants and only present at a low rate in subtypes B, C and D and recombinants CRF01_AE and CRF14_BG, ranging from one to five per variant. Three secondary INI-R changes appeared with variable frequency in INI-naive individuals carrying specific HIV-1 variants: L74M in CRF43_02G (33.3%); T97A in group P (50%), J (33.3%), CRF18_cpx (20%) and F2 (11.5%); and G163RK in CRF44_BF (100%), CRF46_BF (66.7%), CRF17_BF (28.6%), F1 (21.7%), CRF12_BF (16.7%) and CRF29_BF (12.5%). Rare mutations were absent. CONCLUSIONS: Natural variability in INI-R positions across HIV-1 variants should be studied as they may facilitate or delay the emergence of INI-R viruses. PMID- 26546671 TI - Measurement of true ileal calcium digestibility in meat and bone meal for broiler chickens using the direct method. AB - The objective of the study that is presented herein was to determine the true ileal calcium (Ca) digestibility in meat and bone meal (MBM) for broiler chickens using the direct method. Four MBM samples (coded as MBM-1, MBM-2, MBM-3 and MBM 4) were obtained and analyzed for nutrient composition, particle size distribution and bone to soft tissue ratio. The Ca concentrations of MBM-1, MBM 2, MBM-3 and MBM-4 were determined to be 71, 118, 114 and 81 g/kg, respectively. The corresponding geometric mean particle diameters and bone to soft tissue ratios were 0.866, 0.622, 0.875 and 0.781 mm, and 1:1.49, 1:0.98, 1:0.92 and 1:1.35, respectively. Five experimental diets, including four diets with similar Ca concentration (8.3 g/kg) from each MBM and a Ca and phosphorus-free diet, were developed. Meat and bone meal served as the sole source of Ca in the MBM diets. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to six replicate cages (eight birds per cage) and offered from d 28 to 31 post-hatch. Apparent ileal Ca digestibility was calculated by the indicator method and corrected for ileal endogenous Ca losses to determine the true ileal Ca digestibility. Ileal endogenous Ca losses were determined to be 88 mg/kg dry matter intake. True ileal Ca digestibility coefficients of MBM-1, MBM-2, MBM-3 and MBM-4 were determined to be 0.560, 0.446, 0.517 and 0.413, respectively. True Ca digestibility of MBM-1 was higher (P < 0.05) than MBM-2 and MBM-4 but similar (P > 0.05) to that of MBM 3. True Ca digestibility of MBM-2 was similar (P > 0.05) to MBM-3 and MBM-4, while that of MBM-3 was higher (P < 0.05) than MBM-4. These results demonstrated that the direct method can be used for the determination of true Ca digestibility in feed ingredients and that Ca in MBM is not highly available as often assumed. The variability in true Ca digestibility of MBM samples could not be attributed to Ca content, percentage bones or particle size. PMID- 26546670 TI - Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposons. AB - Substantial proportions of mammalian genomes comprise repetitive elements including endogenous retrotransposons. Although these play diverse roles during development, their appropriate silencing is critically important in maintaining genomic integrity in the host cells. The major mechanism for retrotransposon silencing is DNA methylation, but the wave of global DNA demethylation that occurs after fertilization renders preimplantation embryos exceptionally hypomethylated. Here, we show that hypomethylated preimplantation mouse embryos are protected from retrotransposons by repressive histone modifications mediated by the histone chaperone chromatin assembly factor 1 (CAF-1). We found that knockdown of CAF-1 with specific siRNA injections resulted in significant up regulation of the retrotransposons long interspersed nuclear element 1, short interspersed nuclear element B2, and intracisternal A particle at the morula stage. Concomitantly, increased histone H2AX phosphorylation and developmental arrest of the majority (>95%) of embryos were observed. The latter was caused at least in part by derepression of retrotransposons, as treatment with reverse transcriptase inhibitors rescued some embryos. Importantly, ChIP analysis revealed that CAF-1 mediated the replacement of H3.3 with H3.1/3.2 at the retrotransposon regions. This replacement was associated with deposition of repressive histone marks, including trimethylation of histone H3 on lysine 9 (H3K9me3), H3K9me2, H3K27me3, and H4K20me3. Among them, H4K20me3 and H3K9me3 seemed to play predominant roles in retrotransposon silencing, as assessed by knockdown of specific histone methyltransferases and forced expression of unmethylatable mutants of H3.1K9 and H4K20. Our data thus indicate that CAF-1 is an essential guardian of the genome in preimplantation mouse embryos by deposition of repressive histone modifications via histone variant replacement. PMID- 26546672 TI - A novel phosphorylation site at Ser130 adjacent to the pseudosubstrate domain contributes to the activation of protein kinase C-delta. AB - Protein kinase C-delta (PKCdelta) is a signalling kinase that regulates many cellular responses. Although most studies focus on allosteric mechanisms that activate PKCdelta at membranes, PKCdelta also is controlled via multi-site phosphorylation [Gong et al. (2015) Mol. Cell. Biol. 35: , 1727-1740]. The present study uses MS-based methods to identify PKCdelta phosphorylation at Thr(50) and Ser(645) (in resting and PMA-treated cardiomyocytes) as well as Thr(37), Thr(38), Ser(130), Thr(164), Thr(211), Thr(215), Ser(218), Thr(295), Ser(299) and Thr(656) (as sites that increase with PMA). We focused on the consequences of phosphorylation at Ser(130) and Thr(141) (sites just N-terminal to the pseudosubstrate domain). We show that S130D and T141E substitutions co operate to increase PKCdelta's basal lipid-independent activity and that Ser(130)/Thr(141) di-phosphorylation influences PKCdelta's substrate specificity. We recently reported that PKCdelta preferentially phosphorylates substrates with a phosphoacceptor serine residue and that this is due to constitutive phosphorylation at Ser(357), an ATP-positioning G-loop site that limits PKCdelta's threonine kinase activity [Gong et al. (2015) Mol. Cell. Biol. 35: , 1727-1740]. The present study shows that S130D and T141E substitutions increase PKCdelta's threonine kinase activity indirectly by decreasing G loop phosphorylation at Ser(357). A S130F substitution [that mimics a S130F single-nt polymorphism (SNP) identified in some human populations] also increases PKCdelta's maximal lipid-dependent catalytic activity and confers threonine kinase activity. Finally, we show that Ser(130)/Thr(141) phosphorylations relieve auto-inhibitory constraints that limit PKCdelta's activity and substrate specificity in a cell-based context. Since phosphorylation sites map to similar positions relative to the pseudosubstrate domains of other PKCs, our results suggest that phosphorylation in this region of the enzyme may constitute a general mechanism to control PKC isoform activity. PMID- 26546673 TI - Bacillus subtilis delta Factor Functions as a Transcriptional Regulator by Facilitating the Open Complex Formation. AB - Most bacterial RNA polymerases (RNAP) contain five conserved subunits, viz. 2alpha, beta, beta', and omega. However, in many Gram-positive bacteria, especially in fermicutes, RNAP is associated with an additional factor, called delta. For over three decades since its identification, it had been thought that delta functioned as a subunit of RNAP to enhance the level of transcripts by recycling RNAP. In support of the previous observations, we also find that delta is involved in recycling of RNAP by releasing the RNA from the ternary complex. We further show that delta binds to RNA and is able to recycle RNAP when the length of the nascent RNA reaches a critical length. However, in this work we decipher a new function of delta. Performing biochemical and mutational analysis, we show that Bacillus subtilis delta binds to DNA immediately upstream of the promoter element at A-rich sequences on the abrB and rrnB1 promoters and facilitates open complex formation. As a result, delta facilitates RNAP to initiate transcription in the second scale, compared with minute scale in the absence of delta. Using transcription assay, we show that delta-mediated recycling of RNAP cannot be the sole reason for the enhancement of transcript yield. Our observation that delta does not bind to RNAP holo enzyme but is required to bind to DNA upstream of the -35 promoter element for transcription activation suggests that delta functions as a transcriptional regulator. PMID- 26546674 TI - Cooperative Binding of Stromal Interaction Molecule 1 (STIM1) to the N and C Termini of Calcium Release-activated Calcium Modulator 1 (Orai1). AB - Calcium flux through store-operated calcium entry is a central regulator of intracellular calcium signaling. The two key components of the store-operated calcium release-activated calcium channel are the Ca(2+)-sensing protein stromal interaction molecule 1 (STIM1) and the channel pore-forming protein Orai1. During store-operated calcium entry activation, calcium depletion from the endoplasmic reticulum triggers a series of conformational changes in STIM1 that unmask a minimal Orai1-activating domain (CRAC activation region (CAD)). To gate Orai1 channels, the exposed STIM1-activating domain binds to two sites in Orai1, one in the N terminus and one in the C terminus. Whether the two sites operate as distinct binding domains or cooperate in CAD binding is unknown. In this study, we show that the N and C-terminal domains of Orai1 synergistically contribute to the interaction with STIM1 and couple STIM1 binding with channel gating and modulation of ion selectivity. PMID- 26546675 TI - Specificity of Collybistin-Phosphoinositide Interactions: IMPACT OF THE INDIVIDUAL PROTEIN DOMAINS. AB - The regulatory protein collybistin (CB) recruits the receptor-scaffolding protein gephyrin to mammalian inhibitory glycinergic and GABAergic postsynaptic membranes in nerve cells. CB is tethered to the membrane via phosphoinositides. We developed an in vitro assay based on solid-supported 1-palmitoyl-2-oleoyl-sn glycero-3-phosphocholine membranes doped with different phosphoinositides on silicon/silicon dioxide substrates to quantify the binding of various CB2 constructs using reflectometric interference spectroscopy. Based on adsorption isotherms, we obtained dissociation constants and binding capacities of the membranes. Our results show that full-length CB2 harboring the N-terminal Src homology 3 (SH3) domain (CB2SH3+) adopts a closed and autoinhibited conformation that largely prevents membrane binding. This autoinhibition is relieved upon introduction of the W24A/E262A mutation, which conformationally "opens" CB2SH3+ and allows the pleckstrin homology domain to properly bind lipids depending on the phosphoinositide species with a preference for phosphatidylinositol 3 monophosphate and phosphatidylinositol 4-monophosphate. This type of membrane tethering under the control of the release of the SH3 domain of CB is essential for regulating gephyrin clustering. PMID- 26546676 TI - The Inhibitory Mechanism of the zeta Subunit of the F1FO-ATPase Nanomotor of Paracoccus denitrificans and Related alpha-Proteobacteria. AB - The zeta subunit is a novel inhibitor of the F1FO-ATPase of Paracoccus denitrificans and related alpha-proteobacteria. It is different from the bacterial (epsilon) and mitochondrial (IF1) inhibitors. The N terminus of zeta blocks rotation of the gamma subunit of the F1-ATPase of P. denitrificans (Zarco Zavala, M., Morales-Rios, E., Mendoza-Hernandez, G., Ramirez-Silva, L., Perez Hernandez, G., and Garcia-Trejo, J. J. (2014) FASEB J. 24, 599-608) by a hitherto unknown quaternary structure that was first modeled here by structural homology and protein docking. The F1-ATPase and F1-zeta models of P. denitrificans were supported by cross-linking, limited proteolysis, mass spectrometry, and functional data. The final models show that zeta enters into F1-ATPase at the open catalytic alphaE/betaE interface, and two partial gamma rotations lock the N terminus of zeta in an "inhibition-general core region," blocking further gamma rotation, while the zeta globular domain anchors it to the closed alphaDP/betaDP interface. Heterologous inhibition of the F1-ATPase of P. denitrificans by the mitochondrial IF1 supported both the modeled zeta binding site at the alphaDP/betaDP/gamma interface and the endosymbiotic alpha-proteobacterial origin of mitochondria. In summary, the zeta subunit blocks the intrinsic rotation of the nanomotor by inserting its N-terminal inhibitory domain at the same rotor/stator interface where the mitochondrial IF1 or the bacterial epsilon binds. The proposed pawl mechanism is coupled to the rotation of the central gamma subunit working as a ratchet but with structural differences that make it a unique control mechanism of the nanomotor to favor the ATP synthase activity over the ATPase turnover in the alpha-proteobacteria. PMID- 26546677 TI - Cytokine Activation by Antibody Fragments Targeted to Cytokine-Receptor Signaling Complexes. AB - Exogenous cytokine therapy can induce systemic toxicity, which might be prevented by activating endogenously produced cytokines in local cell niches. Here we developed antibody-based activators of cytokine signaling (AcCS), which recognize cytokines only when they are bound to their cell surface receptors. AcCS were developed for type I interferons (IFNs), which induce cellular activities by binding to cell surface receptors IFNAR1 and IFNAR2. As a potential alternative to exogenous IFN therapy, AcCS were shown to potentiate the biological activities of natural IFNs by ~100-fold. Biochemical and structural characterization demonstrates that the AcCS stabilize the IFN-IFNAR2 binary complex by recognizing an IFN-induced conformational change in IFNAR2. Using IFN mutants that disrupt IFNAR1 binding, AcCS were able to enhance IFN antiviral potency without activating antiproliferative responses. This suggests AcCS can be used to manipulate cytokine signaling for basic science and possibly for therapeutic applications. PMID- 26546678 TI - Antiviral Cystine Knot alpha-Amylase Inhibitors from Alstonia scholaris. AB - Cystine knot alpha-amylase inhibitors are cysteine-rich, proline-rich peptides found in the Amaranthaceae and Apocynaceae plant species. They are characterized by a pseudocyclic backbone with two to four prolines and three disulfides arranged in a knotted motif. Similar to other knottins, cystine knot alpha amylase inhibitors are highly resistant to degradation by heat and protease treatments. Thus far, only the alpha-amylase inhibition activity has been described for members of this family. Here, we show that cystine knot alpha amylase inhibitors named alstotides discovered from the Alstonia scholaris plant of the Apocynaceae family display antiviral activity. The alstotides (As1-As4) were characterized by both proteomic and genomic methods. All four alsotides are novel, heat-stable and enzyme-stable and contain 30 residues. NMR determination of As1 and As4 structures reveals their conserved structural fold and the presence of one or more cis-proline bonds, characteristics shared by other cystine knot alpha-amylase inhibitors. Genomic analysis showed that they contain a three-domain precursor, an arrangement common to other knottins. We also showed that alstotides are antiviral and cell-permeable to inhibit the early phase of infectious bronchitis virus and Dengue infection, in addition to their ability to inhibit alpha-amylase. Taken together, our results expand membership of cystine knot alpha-amylase inhibitors in the Apocynaceae family and their bioactivity, functional promiscuity that could be exploited as leads in developing therapeutics. PMID- 26546679 TI - Sar1 GTPase Activity Is Regulated by Membrane Curvature. AB - The majority of biosynthetic secretory proteins initiate their journey through the endomembrane system from specific subdomains of the endoplasmic reticulum. At these locations, coated transport carriers are generated, with the Sar1 GTPase playing a critical role in membrane bending, recruitment of coat components, and nascent vesicle formation. How these events are appropriately coordinated remains poorly understood. Here, we demonstrate that Sar1 acts as the curvature-sensing component of the COPII coat complex and highlight the ability of Sar1 to bind more avidly to membranes of high curvature. Additionally, using an atomic force microscopy-based approach, we further show that the intrinsic GTPase activity of Sar1 is necessary for remodeling lipid bilayers. Consistent with this idea, Sar1 mediated membrane remodeling is dramatically accelerated in the presence of its guanine nucleotide-activating protein (GAP), Sec23-Sec24, and blocked upon addition of guanosine-5'-[(beta,gamma)-imido]triphosphate, a poorly hydrolysable analog of GTP. Our results also indicate that Sar1 GTPase activity is stimulated by membranes that exhibit elevated curvature, potentially enabling Sar1 membrane scission activity to be spatially restricted to highly bent membranes that are characteristic of a bud neck. Taken together, our data support a stepwise model in which the amino-terminal amphipathic helix of GTP-bound Sar1 stably penetrates the endoplasmic reticulum membrane, promoting local membrane deformation. As membrane bending increases, Sar1 membrane binding is elevated, ultimately culminating in GTP hydrolysis, which may destabilize the bilayer sufficiently to facilitate membrane fission. PMID- 26546681 TI - The Redox State Regulates the Conformation of Rv2466c to Activate the Antitubercular Prodrug TP053. AB - Rv2466c is a key oxidoreductase that mediates the reductive activation of TP053, a thienopyrimidine derivative that kills replicating and non-replicating Mycobacterium tuberculosis, but whose mode of action remains enigmatic. Rv2466c is a homodimer in which each subunit displays a modular architecture comprising a canonical thioredoxin-fold with a Cys(19)-Pro(20)-Trp(21)-Cys(22) motif, and an insertion consisting of a four alpha-helical bundle and a short alpha-helical hairpin. Strong evidence is provided for dramatic conformational changes during the Rv2466c redox cycle, which are essential for TP053 activity. Strikingly, a new crystal structure of the reduced form of Rv2466c revealed the binding of a C terminal extension in alpha-helical conformation to a pocket next to the active site cysteine pair at the interface between the thioredoxin domain and the helical insertion domain. The ab initio low-resolution envelopes obtained from small angle x-ray scattering showed that the fully reduced form of Rv2466c adopts a "closed" compact conformation in solution, similar to that observed in the crystal structure. In contrast, the oxidized form of Rv2466c displays an "open" conformation, where tertiary structural changes in the alpha-helical subdomain suffice to account for the observed conformational transitions. Altogether our structural, biochemical, and biophysical data strongly support a model in which the formation of the catalytic disulfide bond upon TP053 reduction triggers local structural changes that open the substrate binding site of Rv2466c allowing the release of the activated, reduced form of TP053. Our studies suggest that similar structural changes might have a functional role in other members of the thioredoxin-fold superfamily. PMID- 26546680 TI - Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual specificity Phosphatase 1 (DUSP1): IMPLICATIONS FOR REGULATION BY GLUCOCORTICOIDS. AB - TNF is central to inflammation and may play a role in the pathogenesis of asthma. The 3'-untranslated region of the TNF transcript contains AU-rich elements (AREs) that are targeted by the RNA-binding protein, tristetraprolin (also known as zinc finger protein 36 (ZFP36)), which is itself up-regulated by inflammatory stimuli, to promote mRNA degradation. Using primary human bronchial epithelial and pulmonary epithelial A549 cells, we confirm that interleukin-1beta (IL1B) induces expression of dual-specificity phosphatase 1 (DUSP1), ZFP36, and TNF. Whereas IL1B-induced DUSP1 is involved in feedback control of MAPK pathways, ZFP36 exerts negative (incoherent) feed-forward control of TNF mRNA and protein expression. DUSP1 silencing increased IL1B-induced ZFP36 expression at 2 h and profoundly repressed TNF mRNA at 6 h. This was partly due to increased TNF mRNA degradation, an effect that was reduced by ZFP36 silencing. This confirms a regulatory network, whereby DUSP1-dependent negative feedback control reduces feed-forward control by ZFP36. Conversely, whereas DUSP1 overexpression and inhibition of MAPKs prevented IL1B-induced expression of ZFP36, this was associated with increased TNF mRNA expression at 6 h, an effect that was predominantly due to elevated transcription. This points to MAPK-dependent feed-forward control of TNF involving ZFP36-dependent and -independent mechanisms. In terms of repression by dexamethasone, neither silencing of DUSP1, silencing of ZFP36, nor silencing of both together prevented the repression of IL1B-induced TNF expression, thereby demonstrating the need for further repressive mechanisms by anti-inflammatory glucocorticoids. In summary, these data illustrate why understanding the competing effects of feedback and feed-forward control is relevant to the development of novel anti-inflammatory therapies. PMID- 26546683 TI - Comment on "Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins". PMID- 26546682 TI - Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis. AB - We performed untargeted metabolomics in plasma of B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation, and membrane stability were observed to be significantly altered between EAE and control (p < 0.05, false discovery rate <0.10). Bioinformatics analysis revealed six metabolic pathways being impacted and altered in EAE, including alpha-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including omega-3 and omega-6 fatty acids, are commonly decreased in mouse models of multiple sclerosis (MS) and in patients with MS. Daily oral administration of resolvin D1, a downstream metabolite of omega-3, decreased disease progression by suppressing autoreactive T cells and inducing an M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of metabolomics to identify an endogenous metabolite(s) possessing drug-like properties, which is assessed for therapy in preclinical mouse models of MS. PMID- 26546684 TI - Response to Comment on "Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins". PMID- 26546685 TI - Comment on "Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice". PMID- 26546686 TI - Response to Comment on "Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice". PMID- 26546687 TI - CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology. AB - CD (cluster of differentiation) Ags are cell surface molecules expressed on leukocytes and other cells relevant for the immune system. CD nomenclature has been universally adopted by the scientific community and is officially approved by the International Union of Immunological Societies and sanctioned by the World Health Organization. It provides a unified designation system for mAbs, as well as for the cell surface molecules that they recognize. This nomenclature was established by the Human Leukocyte Differentiation Antigens Workshops. In addition to defining the CD nomenclature, these workshops have been instrumental in identifying and determining the expression and function of cell surface molecules. Over the past 30 y, the data generated by the 10 Human Leukocyte Differentiation Antigens Workshops have led to the characterization and formal designation of more than 400 molecules. CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stages. mAbs against these molecules have proven to be essential for biomedical research and diagnosis, as well as in biotechnology. More recently, they have been recognized as invaluable tools for the treatment of several malignancies and autoimmune diseases. In this article, we describe how the CD nomenclature was established, present the official updated list of CD molecules, and provide a rationale for their usefulness in the 21st century. PMID- 26546689 TI - An adaptive kernel smoothing method for classifying Austrosimulium tillyardianum (Diptera: Simuliidae) larval instars. AB - In insects, the frequency distribution of the measurements of sclerotized body parts is generally used to classify larval instars and is characterized by a multimodal overlap between instar stages. Nonparametric methods with fixed bandwidths, such as histograms, have significant limitations when used to fit this type of distribution, making it difficult to identify divisions between instars. Fixed bandwidths have also been chosen somewhat subjectively in the past, which is another problem. In this study, we describe an adaptive kernel smoothing method to differentiate instars based on discontinuities in the growth rates of sclerotized insect body parts. From Brooks' rule, we derived a new standard for assessing the quality of instar classification and a bandwidth selector that more accurately reflects the distributed character of specific variables. We used this method to classify the larvae of Austrosimulium tillyardianum (Diptera: Simuliidae) based on five different measurements. Based on head capsule width and head capsule length, the larvae were separated into nine instars. Based on head capsule postoccipital width and mandible length, the larvae were separated into 8 instars and 10 instars, respectively. No reasonable solution was found for antennal segment 3 length. Separation of the larvae into nine instars using head capsule width or head capsule length was most robust and agreed with Crosby's growth rule. By strengthening the distributed character of the separation variable through the use of variable bandwidths, the adaptive kernel smoothing method could identify divisions between instars more effectively and accurately than previous methods. PMID- 26546691 TI - Myostatin induces DNA damage in skeletal muscle of streptozotocin-induced type 1 diabetic mice. PMID- 26546690 TI - Trousseau's syndrome: cancer-associated thrombosis. AB - Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants. PMID- 26546688 TI - APOBEC3 Proteins in Viral Immunity. AB - Apolipoprotein B editing complex 3 family members are cytidine deaminases that play important roles in intrinsic responses to infection by retroviruses and have been implicated in the control of other viruses, such as parvoviruses, herpesviruses, papillomaviruses, hepatitis B virus, and retrotransposons. Although their direct effect on modification of viral DNA has been clearly demonstrated, whether they play additional roles in innate and adaptive immunity to viruses is less clear. We review the data regarding the various steps in the innate and adaptive immune response to virus infection in which apolipoprotein B editing complex 3 proteins have been implicated. PMID- 26546692 TI - Cysteine-independent catalase-like activity of vertebrate peroxiredoxin 1 (Prx1). PMID- 26546693 TI - TNF-TNFR2/p75 signaling inhibits early and increases delayed nontargeted effects in bone marrow-derived endothelial progenitor cells. PMID- 26546694 TI - Nitroxides protect against peroxynitrite-induced nitration and oxidation. AB - Nitroxides are promising compounds for prevention of undesired protein modifications. The aim of this study was to compare the efficiency of 11 nitroxides, derivatives of 2,2,6,6-tetramethylpiperidine-1-oxide (TEMPO) and 2,2,5,5-tetramethylpirrolidine-1-oxyl (PROXYL) in prevention of nitration and oxidation of model compounds and human serum albumin (HSA). Most nitroxides were very efficient in preventing loss of fluorescein fluorescence induced by peroxynitrite (PN) (IC50 in the nanomolar range) and preventing HSA nitration. The loss of fluorescein fluorescence was demonstrated to be due to nitration. Nitroxides were more effective in prevention nitration than oxidation reactions. They showed a concentration window for preventing dihydrorhodamine (DHR) 123 oxidation but exerted a prooxidant effect at both high and low concentrations. No prooxidant effect of nitroxides was seen in prevention of DHR123 oxidation induced by SIN-1. In all essays hydrophobic nitroxides (especially 4-nonylamido TEMPO and 3-carbamolyl-dehydroPROXYL) showed the lowest efficiency. An exception was the prevention of thiol group oxidation by PN and SIN-1 where hydrophobic nitroxides were the most effective, apparently due to binding to the protein. Nitroxides showed low toxicity to MCF-7 cells. Most nitroxides, except for the most hydrophobic ones, protected cells from the cytotoxic action of SIN-1 and SIN 1-induced protein nitration. These results point to potential usefulness of nitroxides for prevention of PN-induced oxidation and, especially, nitration. PMID- 26546696 TI - Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models. AB - Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-MUCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES. PMID- 26546695 TI - Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption. AB - Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis. PMID- 26546698 TI - Recovery and separation of sulfuric acid and iron from dilute acidic sulfate effluent and waste sulfuric acid by solvent extraction and stripping. AB - The recovery and simultaneous separation of sulfuric acid and iron from dilute acidic sulfate effluent (DASE) and waste sulfuric acid (WSA) have been an earnest wish for researchers and the entire sulfate process-based titanium pigment industry. To reduce the pollution of the waste acid and make a comprehensive use of the iron and sulfuric acid in it, a new environmentally friendly recovery and separation process for the DASE and the WSA is proposed. This process is based on the reactive extraction of sulfuric acid and Fe(III) from the DASE. Simultaneously, stripping of Fe(III) is carried out in the loaded organic phase with the WSA. Compared to the conventional ways, this innovative method allows the effective extraction of sulfuric acid and iron from the DASE, and the stripping of Fe(III) from the loaded organic phase with the WSA. Trioctylamine (TOA) and tributyl phosphate (TBP) in kerosene (10-50%) were used as organic phases for solvent extraction. Under the optimal conditions, about 98% of Fe(III) and sulfuric acid were removed from the DASE, and about 99.9% of Fe(III) in the organic phase was stripped with the WSA. PMID- 26546697 TI - Orthogonal optimization of prokaryotic expression of a natural snake venom phospholipase A2 inhibitor from Sinonatrix annularis. AB - Phospholipase A2 (PLA2) is a calcium-dependent enzyme that is involved in inflammatory processes such as the liberation of free arachidonic acid from the membrane pool for the biosynthesis of eicosanoids. Snake venom are known containing PLA2s (svPLA2s) which exhibit a wide variety of pharmacological effects including neurotoxicity, cardiotoxicity, myotoxicity and hemorrhage. Therefore, inhibition of svPLA2 would be advantageous to successful envenomation treatment. A gamma type PLI (PLA2 inhibitor) has been extracted from the serum of Sinonatrix annularis, a non-venomous snake indigenous to China. This showed strong inhibition of Deinagkistrrodon acutus PLA2, however, the PLIgamma level in the serum and snake resource are not sufficiently sustainable for further research. To overcome these limitations, we constructed a His6-PLIgamma pET28 fusion expression vector and transformed Escherichia coli BL21. To improve the expression of PLIgamma, an orthogonal experiment [L16(4)(5)] was performed to optimize induction parameters. The optimized condition was determined to be: induction by 0.4 mM isopropyl-beta-D-thiogalactoside (IPTG) for 6 h to the recombinant BL21 after its OD600 was 0.8, with continuous shaking cultivation at 190 rpm and 35 degrees C. Under these conditions, the amount of expressed protein could reach 57 mg/L. The His6-PLIgamma was purified by nickel affinity chromatography and renatured by On-column refolding. The resulting PLIgamma showed a good inhibitory effect of enzymatic activities to venom PLA2 isolated from D. acutus. Moreover, the PLIgamma had a wide anti-hemorrhage activities to D. acutus, Naja atra and Agkistrodon halys venom. PMID- 26546699 TI - Effects of flue gas components on removal of elemental mercury over Ce-MnOx/Ti PILCs. AB - The adsorption and oxidation of elemental mercury (Hg(0)) under various flue gas components were investigated over a series of Ce-MnOx/Ti-PILC catalysts, which were synthesized by an impregnation method. To discuss the mechanism, the catalysts were characterized by various techniques such as N2 adsorption desorption, scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) analysis and X-ray photoelectron spectroscopy (XPS). The results indicated that the presence of 500 ppm SO2 in the flue gas significantly restrained the Hg(0) adsorption and oxidation over 6%Ce-6%MnOx/Ti PILC due to the formation of SO4(2-) species. Hg(0) could be oxidized to HgCl2 in the presence of HCl, because the Deacon process occurred. NO would react with active oxygen to form NO2-containing species, which facilitated Hg(0) oxidation. While the presence of NO limited the Hg(0) adsorption on 6%Ce-6%MnOx/Ti-PILC due to the competitive adsorption of NO with Hg(0). The addition of NH3 in the flue gas significantly restrained Hg(0) adsorption and oxidation, because the formed NH4(+) species covered the active adsorption sites on the surfaces, and further limited Hg(0) oxidation. However, when NO and NH3 were simultaneously added into the flue gas, the Hg(0) oxidation efficiency of 6%Ce-6%MnOx/Ti-PILC exhibited a relatively high value (72%) at 250 degrees C, which indicated the practicability to use Ce-MnOx/Ti-PILC for Hg(0) removal under SCR conditions. PMID- 26546700 TI - Behavior of antibiotics and antibiotic resistance genes in eco-agricultural system: A case study. AB - This study aims to determine abundance and persistence of antibiotics and antibiotic resistance genes (ARGs) in eco-agricultural system (EAS), which starts from swine feces to anaerobic digestion products, then application of anaerobic digestion solid residue (ADSR) and anaerobic digestion liquid residue (ADLR) to the soil to grow ryegrass, one of swine feed. Oxytetracycline had the highest concentration in manure reaching up to 138.7 mg/kg. Most of antibiotics could be effectively eliminated by anaerobic digestion and removal rates ranged from 11% to 86%. ARGs abundance fluctuated within EAS. TetQ had the highest relative abundance and the relative abundance of tetG had the least variation within the system, which indicates that tetG is persistent in the agricultural environment and requires more attention. Compared to the relative abundance in manure, tetC and tetM increased in biogas residue while three ribosomal protection proteins genes (tetO, tetQ, tetW) decreased (p<0.05), with other genes showing no significant change after anaerobic fermentation (p>0.05). Most ARGs in downstream components (soils and fishpond) of EAS showed significantly higher relative abundance than the control agricultural system (p<0.05), except for tetG and sulI. PMID- 26546701 TI - Brominated flame retardants and the formation of dioxins and furans in fires and combustion. AB - The widespread use and increasing inventory of brominated flame retardants (BFRs) have caused considerable concern, as a result of BFRs emissions to the environment and of the formation of both polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) and mixed polybromochloro-dibenzo-p-dioxins and dibenzofurans (PBCDD/Fs or PXDD/Fs). Structural similarities between PBDD/Fs and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) suggest the existence of comparable formation pathways of both PBDD/Fs and PCDD/Fs, yet BFRs also act as specific precursors to form additional PBDD/Fs. Moreover, elementary bromine (Br2) seems to facilitate chlorination by bromination of organics, followed by Br/Cl-exchange based on displacement through the more reactive halogen. Overall, PBDD/Fs form through three possible pathways: precursor formation, de novo formation, and dispersion of parts containing BFRs as impurities and surviving a fire or other events. The present review summarises the formation mechanisms of both brominated (PBDD/Fs) and mixed dioxins (PXDD/Fs with X=Br or Cl) from BFRs, recaps available emissions data of PBDD/Fs and mixed PXDD/Fs from controlled waste incineration, uncontrolled combustion sources and accidental fires, and identifies and analyses the effects of several local factors of influence, affecting the formation of PBDD/Fs and mixed PXDD/Fs during BFRs combustion. PMID- 26546702 TI - The influence of biochar type on long-term stabilization for Cd and Cu in contaminated paddy soils. AB - Long-term effect of biochar on PTEs (potential toxic elements) immobilization depends upon biochar own property and its aging process in soil. To understand the role of biachar type on PTEs stabilization, two types of biochar, corn-straw derived biochar (CB) and hardwood-derived biochar (HB), were compared for their efficacy in achieving a stable decrease in the bio-availability of Cd and Cu in soils. The 3-year pot-culture experiment showed that HB reduced the concentration of CaCl2-extractable Cd and Cu by 57.9 and 63.8% in soil, and Cd and Cu uptake by 63.6 and 56.3% in rice tissue respectively, in the first year, whereas these values increased in the next two years. On the other hand, CB decreased these values steadily year by year. At the end of the 3 years, CB at 5% level had lowered the levels of CaCl2-extractable Cd and Cu by 53.6 and 66.8%, respectively. These variations between CB and HB were due to the differences in the way the two types of biochar age in the soil. The aging process was simulated in the laboratory, and the XPS results showed that the oxidization of the biochars introduced more oxygen-containing groups (especially carboxyl) on the surface of CB than HB, leading to a correspondingly greater number of oxygenated binding sites for Cd and Cu in the case of CB. The content of lignin was the major factor resulting in the variation of oxidation degree in two biochars. These results suggest that it is important to select the right kind of biochar to stably decrease the bio-availability of potential toxic elements (Cd and Cu) in contaminated soils. PMID- 26546703 TI - Variations in the fate and biological effects of sulfamethoxazole, norfloxacin and doxycycline in different vegetable-soil systems following manure application. AB - The fate of sulfamethoxazole (SMZ), norfloxacin (NOR) and doxycycline (DOX) and their biological effects in radish and pakchoi culture systems were investigated. DOX dissipated more rapidly than SMZ and NOR, while radish and pakchoi cultivation increased the removal of residual DOX in soils. Dissipation of NOR was accelerated in radish soils but was slowed down slightly in pakchoi soils. Vegetable cultivation exerted an insignificant effect on SMZ removal. Investigation of antibiotic bioaccumulation showed that the uptake of DOX by radish and pakchoi was undetectable, but the radish accumulated more SMZ and NOR than pakchoi. Among the three antibiotics, only SMZ use exhibited an apparent suspension of plant seed germination, up-ground plant growth and soil microbial diversity. Pakchoi responded more sensitively to SMZ than did the radish. Principal component analysis (PCA) based on MicroRESPTM indicated that the sampling time and antibiotic treatments could influence the soil microbial community. Only in the pakchoi soils did antibiotic application exert a more robust effect on the microbial community than the sampling time; SMZ treatments and DOX treatments could be clearly discriminated from the control treatments. These results are crucial for an assessment of the potential risks of antibiotics to culture system practices and suggest that good agricultural practices help to limit or even reduce antibiotic pollution. PMID- 26546704 TI - Influence of environmental parameters and of their interactions on the release of metal(loid)s from a construction material in hydraulic engineering. AB - Besides the leaching behaviour of a construction material under standardised test specific conditions with laboratory water, for some construction materials it is advisable to test their environmental behaviour also under close to end use conditions. The envisaged end use combined with the product characteristics (e.g. mineral phases) is decisive for the choice of environmental factors that may change the release of substance that potentially cause adverse environmental effects (e.g. fertilisation or ecotoxicity). At the moment an experimental link is missing between mono-factorial standardised test systems and non standardised complex incubation experiments such as mesocosms which are closer to environmental conditions. Multi-factorial batch experiments may have the potential to close the gap. To verify this, batch experiments with copper slag were performed which is used as armour stones in hydraulic engineering. Design of experiments (DoE) was applied to evaluate the impact of pH, ionic strength, temperature and sediment content on the release of As, Cu, Mo, Ni, Pb, Sb and Zn. The study shows that release and sediment-eluent partitioning of metal(loid)s are impacted by interactions between the studied factors. Under the prevalent test conditions sediment acts as a sink enhancing most strongly the release of elements from the material. PMID- 26546705 TI - Fluorescent silver nanoclusters for ultrasensitive determination of chromium(VI) in aqueous solution. AB - In this work, a simple and sensitive Cr(VI) sensor is proposed based on fluorescent polyethyleneimine-stabilized Ag nanoclusters, which allows the determination over a wide concentration range of 0.1 nM-3.0 MUM and with a detection limit as low as 0.04 nMU and a good selectivity. The quenching mechanism was discussed in terms of the absorption and fluorescence spectra, suggesting that Cr(VI) is connected to Ag nanoclusters by hydrogen bond between the oxygen atom at the vertex of tetrahedron structure of Cr(VI) and the amino nitrogen of polyethyleneimine that surrounded Ag nanoclusters and electron transfer from Ag nanoclusters to highly electron-deficient Cr(VI) results in fluorescence quenching. Despite the failure to quench the fluorescence efficiently, Cr(III) can also be measured using the proposed Ag nanoclusters by being oxidized to Cr(VI) in alkaline solution (pH ~ 9) containing H2O2. Therefore, our approach could be used to detect Cr(VI), Cr(III) and the total chromium level in aqueous solution. In addition, Cr(VI) analysis in real water samples were satisfactory, indicating this method could be practically promising for chromium measurements. PMID- 26546706 TI - Models to estimate the minimum ignition temperature of dusts and hybrid mixtures. AB - The minimum ignition temperatures (MIT) of hybrid mixtures have been investigated by performing several series of tests in a modified Godbert-Greenwald furnace. Five dusts as well as three perfect gases and three real were used in different combinations as test samples. Further, seven mathematical models for prediction of the MIT of dust/air mixtures were presented of which three were chosen for deeper study and comparison with the experimental results based on the availability of the input quantities needed and their applicability. Additionally, two alternative models were proposed to calculate the MIT of hybrid mixtures and were validated against the experimental results. A significant decrease of the minimum ignition temperature of either the gas or the vapor as well as an increase in the explosion likelihood could be observed when a small amount of dust which was either below its minimum explosible concentration or not ignitable itself at that particular temperature was mixed with the gas. The various models developed by Cassel, Krishma and Mitsui to predict the MIT of dust were in good agreement with the experimental results as well as the two models proposed to predict the MIT of hybrid mixtures were also in agreement with the experimental value. PMID- 26546707 TI - Micropollutant removal in an algal treatment system fed with source separated wastewater streams. AB - Micropollutant removal in an algal treatment system fed with source separated wastewater streams was studied. Batch experiments with the microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water and synthetic urine were performed to assess the removal of six spiked pharmaceuticals (diclofenac, ibuprofen, paracetamol, metoprolol, carbamazepine and trimethoprim). Additionally, incorporation of these pharmaceuticals and three estrogens (estrone, 17beta-estradiol and ethinylestradiol) into algal biomass was studied. Biodegradation and photolysis led to 60-100% removal of diclofenac, ibuprofen, paracetamol and metoprolol. Removal of carbamazepine and trimethoprim was incomplete and did not exceed 30% and 60%, respectively. Sorption to algal biomass accounted for less than 20% of the micropollutant removal. Furthermore, the presence of micropollutants did not inhibit C. sorokiniana growth at applied concentrations. Algal treatment systems allow simultaneous removal of micropollutants and recovery of nutrients from source separated wastewater. Nutrient rich algal biomass can be harvested and applied as fertilizer in agriculture, as lower input of micropollutants to soil is achieved when algal biomass is applied as fertilizer instead of urine. PMID- 26546708 TI - Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix. AB - Perlecan/HSPG2, a large, monomeric heparan sulfate proteoglycan (HSPG), is a key component of the lacunar canalicular system (LCS) of cortical bone, where it is part of the mechanosensing pericellular matrix (PCM) surrounding the osteocytic processes and serves as a tethering element that connects the osteocyte cell body to the bone matrix. Within the pericellular space surrounding the osteocyte cell body, perlecan can experience physiological fluid flow drag force and in that capacity function as a sensor to relay external stimuli to the osteocyte cell membrane. We previously showed that a reduction in perlecan secretion alters the PCM fiber composition and interferes with bone's response to a mechanical loading in vivo. To test our hypothesis that perlecan core protein can sustain tensile forces without unfolding under physiological loading conditions, atomic force microscopy (AFM) was used to capture images of perlecan monomers at nanoscale resolution and to perform single molecule force measurement (SMFMs). We found that the core protein of purified full-length human perlecan is of suitable size to span the pericellular space of the LCS, with a measured end-to-end length of 170+/-20 nm and a diameter of 2-4 nm. Force pulling revealed a strong protein core that can withstand over 100 pN of tension well over the drag forces that are estimated to be exerted on the individual osteocyte tethers. Data fitting with an extensible worm-like chain model showed that the perlecan protein core has a mean elastic constant of 890 pN and a corresponding Young's modulus of 71 MPa. We conclude that perlecan has physical properties that would allow it to act as a strong but elastic tether in the LCS. PMID- 26546709 TI - Serum pentraxin-3 levels in acute stroke: No association with stroke prognosis. AB - BACKGROUND: Stroke is the leading cause of serious disability. Estimating severity of the disease and early risk assessment is crucial. Several studies have been carried on and several biomarkers have been proposed in the literature for risk assessment and to estimate the stroke prognosis. In this study we assessed the association of predictors such as patient age, gender, stroke volume and NIHS scores on prognosis of stroke event. We investigated whether the serum pentraxin-3 levels are linked with stroke prognosis. METHODS: Forty-four stroke patients without cardiovascular risk factors were included in this study. Initial NIHS scores, stroke volumes, serum pentraxin-3 levels and the data regarding the risk factors were collected in the first and seventh days of event. Association of predictors with final NIHS scores were investigated using multivariate regression model. RESULTS: Initial NIHS score, initial and final stroke volumes were independently associated with final NIHS score whereas serum pentraxin-3 levels, whether acquired at the first or seventh day of stroke, were not associated with final NIHS score. CONCLUSIONS: In stroke patients without cardiovascular, cardiopulmonary and infectious diseases, serum pentraxin-3 levels are not associated with stroke prognosis. PMID- 26546710 TI - Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility. AB - OBJECTIVE: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. METHODS: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. RESULTS: Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% +/- 13.6 increase compared to 57.8% +/- 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa +/- 93.6 versus 621.4 kPa +/- 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. CONCLUSIONS: These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA. PMID- 26546711 TI - Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. AB - Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Chemoprevention, employing the use of natural, dietary or synthetic agents has become an appealing strategy to combat the increasing cases of cancers worldwide. The present study was designed to investigate the mechanism based chemopreventive nature of hesperetin (HSP) against B[a]P induced lung carcinogenesis in Swiss albino mice. We analyzed the chemopreventive potential of HSP by estimating the status of lipid peroxidation (LPO), enzymic (SOD, CAT, GPx, GR, and GST), nonenzymic antioxidants (GSH, Vit C and Vit E), proinflammatory cytokine (TNF-alpha), western blotting (CYP1A1, PCNA, Nrf2 and NF-kappaB expression) and histopathology of lung tissues of control and experimental mice. Administration of B[a]P (50 mg/kg, p.o.) resulted in an increase in lung weight, LPO with concomitant decrease in body weight, enzymic (SOD, CAT, GPx, GR, and GST) and non-enzymic (GSH, Vit C and Vit E) antioxidants. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B[a]P induced mice. Further, elevated levels of TNF-alpha along with activated expression of NF-kappaB, PCNA and CYP1A1, and downregulation of Nrf2 was observed in B[a]P intoxicated animals. Pre- and post-treatment with HSP effectively suppressed B[a]P induced lung carcinoma and the associated preneoplastic lesions by alleviating LPO, modulating antioxidants and decreasing the expression of NF kappaB, PCNA and CYP1A1. These findings demonstrate that HSP possesses a potential chemopreventive activity against B[a]P induced lung cancer and this is attributed to its free radical scavenging, antioxidant, anti-inflammatory and antiproliferative properties. PMID- 26546713 TI - Functional screen for microRNAs of Nilaparvata lugens reveals that targeting of glutamine synthase by miR-4868b regulates fecundity. AB - Insect fecundity is regulated by the interaction of genotypes and the environment. MicroRNAs (miRNAs) also act in insect development and reproduction by regulating genes involved in these physiological processes. Although hundreds of insect miRNAs have been identified, the biological roles of most remain poorly understood. Here, we used a multi-algorithm approach for miRNA target prediction in 3'UTRs of fecundity-related genes in the brown planthopper (BPH) Nilaparvata lugens and identified 38 putative miRNAs targeting 9 fecundity-related genes. High-ranked miRNAs were selected for target validation. Using a dual luciferase reporter assay in S2 cells, we experimentally verified N. lugens glutamine synthetase (NlGS) as an authentic target of microRNA-4868b (miR-4868b). In the females, NlGS protein expression was down-regulated after injection of a miR 4868b mimic but up-regulated after injection of a miR-4868b inhibitor. In addition, overexpression of miR-4868b reduced fecundity, and disrupted ovary development and Vg expression in N. lugens. These findings showed that miR-4868b is involved in regulating N. lugens fecundity by targeting NlGS. Moreover, this study may lead to better understanding of the fecundity of this important agricultural insect pest. PMID- 26546712 TI - Uptake of Marasmius oreades agglutinin disrupts integrin-dependent cell adhesion. AB - BACKGROUND: Fruiting body lectins have been proposed to act as effector proteins in the defense of fungi against parasites and predators. The Marasmius oreades agglutinin (MOA) is a lectin from the fairy ring mushroom with specificity for Galalpha1-3Gal containing carbohydrates. This lectin is composed of an N-terminal carbohydrate-binding domain and a C-terminal dimerization domain. The dimerization domain of MOA shows in addition calcium-dependent cysteine protease activity, similar to the calpain family. METHODS: Cell detachment assay, cell viability assay, immunofluorescence, live cell imaging and Western blot using MDCKII cell line. RESULTS: In this study, we demonstrate in MDCKII cells that after internalization, MOA protease activity induces profound physiological cellular responses, like cytoskeleton rearrangement, cell detachment and cell death. These changes are preceded by a decrease in FAK phosphorylation and an internalization and degradation of beta1-integrin, consistent with a disruption of integrin-dependent cell adhesion signaling. Once internalized, MOA accumulates in late endosomal compartments. CONCLUSION: Our results suggest a possible toxic mechanism of MOA, which consists of disturbing the cell adhesion and the cell viability. GENERAL SIGNIFICANCE: After being ingested by a predator, MOA might exert a protective role by diminishing host cell integrity. PMID- 26546714 TI - Indicators of recent mating success in the pipevine swallowtail butterfly (Battus philenor) and their relationship to male phenotype. AB - A key determinant of the intensity of sexual selection acting on a trait is how variation in that trait is related to variance in reproductive success of individuals. This connection compels efforts to assess lifetime mating number and how it varies among individuals in a population. In the Lepidoptera, female mating success can be assessed relatively easily by counting by the number of spermatophores in the female's copulatory sac but male mating success in the field can often only be documented by observing copulations. Here we report a method for identifying whether or not males have recently mated that relies on the effect of mating on the appearance of the male's reproductive tract in the pipevine swallowtail, Battus philenor. In this species laboratory experiments reveal that during mating, components of a male's reproductive tract become shorter, decrease in mass, and change in appearance, irrespective of male age. These changes persist for at least two days after mating. After documenting these indicators of recent mating, we examined the reproductive tract of 68 field caught males and found that twelve (17.6%) showed strong evidence of having mated recently. We found that older males were more likely to have recently mated. In addition, the color of the dorsal hindwing, a feature that females use in mate choice, was significantly greener in males, that according to our criteria, had recently-mated than in males that had not. PMID- 26546715 TI - Supramolecular organization of bacterial aerobic respiratory chains: From cells and back. AB - Aerobic respiratory chains from all life kingdoms are composed by several complexes that have been deeply characterized in their isolated form. These membranous complexes link the oxidation of reducing substrates to the reduction of molecular oxygen, in a process that conserves energy by ion translocation between both sides of the mitochondrial or prokaryotic cytoplasmatic membranes. In recent years there has been increasing evidence that those complexes are organized as supramolecular structures, the so-called supercomplexes and respirasomes, being available for eukaryotes strong data namely obtained by electron microscopy and single particle analysis. A parallel study has been developed for prokaryotes, based on blue native gels and mass spectrometry analysis, showing that in these more simple unicellular organisms such supercomplexes also exist, involving not only typical aerobic-respiration associated complexes, but also anaerobic-linked enzymes. After a short overview of the data on eukaryotic supercomplexes, we will analyse comprehensively the different types of prokaryotic aerobic respiratory supercomplexes that have been thus far suggested, in both bacteria and archaea. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof Conrad Mullineaux. PMID- 26546716 TI - Characterizing the output settings of dental curing lights. AB - OBJECTIVES: For improved inter-study reproducibility and ultimately improved patient care, researchers and dentists need to know what electromagnetic radiation (light) is emitted from the light-curing unit (LCU) they are using and what is received by the resin. This information cannot be obtained from a dental radiometer, even though many studies have used a dental radiometer. METHODS: The light outputs from six LCUs (two QTH and four broad-spectrum LED units) were collected in real-time using an integrating sphere connected to a fiberoptic spectrometer during different light exposures. RESULTS: It was found that the spectral emissions were unique to each LCU, and there was no standardization in what was emitted on the various ramp (soft-start) settings. Relative to the normal use setting, using the ramp setting reduced the radiant energy (J) delivered from each LCU. For one of the four broad-spectrum LED LCUs, the spectral emissions in the violet range did not increase when the overall radiant power output was increased. In addition, this broad-spectrum LED LCU emitted no light from the violet LED chip for the first 5s and only emitted violet light when the ramp phase finished. CONCLUSIONS: A single irradiance value derived from a dental radiometer or from a laboratory grade power meter cannot adequately describe the output from the LCU. Manufacturers should provide more information about the light output from their LCUs. Ideally, future assessments and research publications that include resin photopolymerization should report the spectral radiant power delivered from the LCU throughout the entire exposure cycle. PMID- 26546717 TI - Vasculitides: Proposal for an integrated nomenclature. AB - The vasculitides form a heterogeneous group of systemic diseases that differ in etiology, histological patterns, and, consequently, clinical significance and prognosis but are traceable to the same pathological event, namely, vessel wall inflammation. The clinical heterogeneity among these diseases, together with yet unknown pathogenetic mechanisms for many of them, creates difficulties in the early diagnosis and correct management of affected patients. Therefore, several groups of investigators have elaborated nomenclatures to set some order in the definition and grouping of the vasculitides. The two main naming systems used for decades, i.e., the Fauci nomenclature and the 1994 Chapel Hill Consensus Conference (CHCC) nomenclature, were recently superseded by a revised CHCC nomenclature published in 2012. The aim of that revision was to update the names and definitions of the vasculitides and to include novel forms, considering the advances in knowledge made since the first consensus conference was held. Here, we critically discuss the 2012 CHCC nomenclature in light of the earlier naming systems and raise some concerns in how several vasculitides were grouped. On the basis of this analysis, we propose an integrated nomenclature that we believe will have a more direct impact in the clinic, perfectly aware that any redefinition may present contradictions. PMID- 26546718 TI - Enzymatic properties of chitinase-producing antagonistic bacterium Paenibacillus chitinolyticus with various substrates. AB - Various chitin substrates were used to investigate the properties of enzymes produced from the chitinase-producing bacterium Paenibacillus chitinolyticus MP 306 against phytopathogens. The MP-306 bacterium was incubated in nine culture media [crab shell powder chitin (CRS), chitin-protein complex powder (CPC), carboxymethyl-chitin powder (CMC), yeast extract only (YE), LB (Trypton, NaCl, and yeast extract), GT (Trypton, NaCl, and glucose), crab shell colloidal chitin (CSC), squid pen powder chitin (SPC), and cicada slough powder chitin (CSP)] at 30 degrees C for 3 days. Chitinase isozymes in CPC medium were expressed strongly as CN1, CN2, CN3, CN4, CN5, and CN6 bands on native-PAGE gels. Chitinase isozymes in CPC and CMC medium were expressed as 13 bands (CS1-CS13) on SDS-PAGE gels. Chitinase isozymes were expressed strongly on SDS-PAGE gels as two bands (CS6 and CS8) on YE and LB medium and 13 bands (CS1-CS13) on SPC medium. In crude enzyme, chitinase isozymes at pH 7 and pH 9 in chitin media appeared strongly on SDS-PAGE gels. Partial purified enzyme indicated high stability of enzyme activity at various temperatures and pHs in chitin medium, while these enzymes indicated low activity staining of enzyme on electrophoresis gels at various temperatures and pHs condition of chitin medium. PMID- 26546719 TI - Biofilm formation in invasive Staphylococcus aureus isolates is associated with the clonal lineage. AB - The contribution of the genetic background of Staphylococcus aureus to biofilm formation is poorly understood. We investigated the association between the genetic background and the biofilm forming ability of clinical invasive S. aureus isolates. Secondary objectives included investigating any correlation with biofilm formation and methicillin resistance or the source of bacteraemia. The study was conducted at a 1300-bed tertiary hospital in Cape Town, South Africa. S. aureus isolates obtained from blood cultures between January 2010 and January 2012 were included. Genotypic characterization was performed by PFGE, spa typing, SCCmec typing and MLST. Thirty genotypically unique strains were assessed for phenotypic biofilm formation with the microtitre plate assay. All isolates were tested in triplicate and an average optical density, measured at a wavelength of 490 nm, was determined. The biofilm forming ability of isolates with A490 <= 0.17 were considered non-adherent, A490 > 0.17 'weak positive' and A490 > 0.34 'strong positive'. Fifty seven percent of isolates formed biofilms. Weak biofilm formation occurred in 40% (n = 12) and strong biofilm formation in 17% (n = 5) of isolates. All 5 isolates capable of strong biofilm formation belong to one spa clonal complex (spa-CC 064). Strains from spa-CC 064 were capable of higher biofilm formation than other spa clonal complexes (p = 0.00002). These 5 strains belonged to MLST CC5 and CC8. Biofilm formation correlates with the spa clonal lineage in our population of invasive S. aureus strains. Biofilm formation did not correlate with methicillin resistance and was not related to the source of bacteraemia. PMID- 26546720 TI - The benefits of coffee on skeletal muscle. AB - Coffee is consumed worldwide with greater than a billion cups of coffee ingested every day. Epidemiological studies have revealed an association of coffee consumption with reduced incidence of a variety of chronic diseases as well as all-cause mortality. Current research has primarily focused on the effects of coffee or its components on various organ systems such as the cardiovascular system, with relatively little attention on skeletal muscle. Summary of current literature suggests that coffee has beneficial effects on skeletal muscle. Coffee has been shown to induce autophagy, improve insulin sensitivity, stimulate glucose uptake, slow the progression of sarcopenia, and promote the regeneration of injured muscle. Much more research is needed to reveal the full scope of benefits that coffee consumption may exert on skeletal muscle structure and function. PMID- 26546721 TI - Inhibition of the interactions between metastatic human breast cancer cells and platelets by beta-nitrostyrene derivatives. AB - AIMS: The interactions between cancer cells and platelets have been recognized to play an important role in cancer progress as well as metastasis, and interference with cancer-platelet interactions is an attractive strategy for cancer therapy. In the present study, two beta-nitrostyrene derivatives: 3, 4-methylene-dioxy beta-nitrostyrene (MNS) and 4-O-benzoyl-3-methoxyl-beta-nitrostyrene (BMNS) have been tested for their inhibitory effect on platelet activation caused by metastatic human breast cancer MDA-MB-231 and Hs578T cells. MAIN METHODS: Washed human platelets were co-incubated with breast cancer cells, and platelet aggregation was determined turbidimetrically. Platelet adhesion to cancer cells and P-selectin expression were measured by flow cytometry. Platelet-derived growth factor (PDGF) released from cancer cell-stimulated platelets was determined by enzyme-linked immunosorbent assay (ELISA). KEY FINDINGS: MNS and BMNS prevented cancer cell-induced platelet aggregation, P-selectin expression, and PDGF secretion. Moreover, the beta-nitrostyrenes reduced platelet adhesion to cancer cells, suggesting the initial cancer-platelet interactions are inhibited. In contrast to current antiplatelet strategies, the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist RGDS peptide only prevented cancer cells-induced platelet aggregation, but not platelet adhesion and secretion; whereas the cyclooxygenase inhibitor aspirin and the adenosine diphosphate (ADP) scavenger apyrase affected neither platelet aggregation nor platelet secretion. SIGNIFICANCE: The inhibitory effects of the beta-nitrostyrene derivatives on cancer-platelet interactions may offer a potential approach for repressing cancer metastasis. PMID- 26546723 TI - Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell. AB - Recent years have seen the description and elucidation of a new class of anti inflammatory and pro-resolving lipid mediators. The arachidonic acid (AA)-derived compounds in this class are called lipoxins and have been described in great detail since their discovery thirty years ago. The new players are mediators derived from fish oil omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), called resolvins, protectins and maresins. Taken together, these mediators are also called specialized pro-resolution mediators (SPMs). As compared to the AA/EPA/DHA-derived compounds, research regarding mediators formed from the n-3 and n-6 docosapentaenoic acids (DPAn-3 and DPAn-6) is sparse. However, mono- di- and trihydroxy derivates of the DPAs have anti inflammatory properties as well, even though mechanisms of their anti inflammatory action have not been fully elucidated. This review aims to summarize current knowledge regarding the DPA-derived SPMs and their actions. PMID- 26546722 TI - Osmolar regulation of endothelin-1 production by the inner medullary collecting duct. AB - AIMS: Endothelin-1 (ET-1) is an autocrine inhibitor of collecting duct (CD) Na(+) and water reabsorption. CD ET-1 production is increased by a high salt diet and is important in promoting a natriuretic response. The mechanisms by which a high salt diet enhances CD ET-1 are being uncovered. In particular, elevated tubule fluid flow, as occurs in salt loading, enhances CD ET-1 synthesis. Tubule fluid solute content and interstitial osmolality can also be altered by a high salt diet, however their effect on CD ET-1 alone, or in combination with flow, is poorly understood. MAIN METHODS: ET-1 mRNA production by a mouse inner medullary CD cell line (mIMCD3) in response to changing flow and/or osmolality was assessed. KEY FINDINGS: Flow or hyperosmolality (using NaCl, mannitol or urea) individually caused an ~2-fold increase in ET-1 mRNA, while flow and hyperosmolality together increased ET-1 mRNA by ~14 fold. The hyperosmolality effect alone and the synergistic effect of flow + hyperosmolality was inhibited by chelation of intracellular Ca(2+), however were not altered by blockade of downstream Ca(2+)-signaling pathways (calcineurin or NFATc), inhibition of cellular Ca(2+) entry channels (purinergic receptors or polycystin-2), or blockade of the epithelial Na(+) channel. Inhibition of NFAT5 with rottlerin or NFAT5 siRNA greatly reduced the stimulatory effect of osmolality alone and osmolality + flow on mIMCD3 ET-1 mRNA levels. SIGNIFICANCE: Both flow and osmolality individually and synergistically stimulate mIMCD3 ET-1 mRNA content. These findings may be relevant to explaining high salt diet induction of CD ET-1 production. PMID- 26546724 TI - NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway. AB - NFAT-133 is an aromatic compound with cinammyl alcohol moiety, isolated from streptomycetes strain PM0324667. We have earlier reported that NFAT-133 increases insulin stimulated glucose uptake in L6 myotubes using a PPARgamma independent mechanism and reduces plasma or blood glucose levels in diabetic mice. Here we investigated the effects of NFAT-133 on cellular signaling pathways leading to glucose uptake in L6 myotubes. Our studies demonstrate that NFAT-133 increases glucose uptake in a dose- and time-dependent manner independent of the effects of insulin. Treatment with Akti-1/2, wortmannin and increasing concentrations of insulin had no effect on NFAT-133 mediated glucose uptake. NFAT-133 induced glucose uptake is completely mitigated by Compound C, an AMPK inhibitor. Further, the kinases upstream of AMPK activation namely; LKB-1 and CAMKKbeta are not involved in NFAT-133 mediated AMPK activation nor does the compound NFAT-133 have any effect on AMPK enzyme activity. Further analysis confirmed that NFAT-133 indirectly activates AMPK by reducing the mitochondrial membrane potential and increasing the ratio of AMP:ATP. PMID- 26546725 TI - Evaluating Sarconesiopsis magellanica blowfly-derived larval therapy and comparing it to Lucilia sericata-derived therapy in an animal model. AB - Larval therapy is used as alternative treatment for hard-to-heal chronic and infected wounds. Lucilia sericata is the most used blowfly species. However, it has been shown recently that Sarconesiopsis magellanica larval excretions and secretions have potent antibacterial activity; this blowfly belongs to the Calliphoridae family. The present work has dealt with evaluating larval therapy using S. magellanica on wounds induced in diabetic rabbits and its action was compared to the effect induced by L. sericata. Twelve New Zealand White rabbits (Oryctolagus cuniculus) were used; they were divided into 4 groups, the first two being treated with larval therapy derived from both aforementioned necrophagous blowflies, an antibiotic was used in the third and the fourth was used as control. All the animals were wounded on the back and infected with Pseudomonas aeruginosa and Staphylococcus aureus. Samples of the secretion from each animal's infected wound were taken and sown on blood agar. The colony forming units were then counted. The PUSH scale was used for the macroscopic evaluation of the wounds. Bacterial control was encountered 48 h post-treatment in the treatments involving larval therapy and to a lesser extent with the antibiotic. Likewise, wound debridement was quicker and more efficient with larval therapy compared to the antibiotic group; however, wound closing time was 23 days in all treatments. The group treated with S. magellanica larvae had relatively quicker evolution until the proliferation phase and the start of maturation, even though there were no significant differences between both blowfly species evaluated here regarding treatments by the end of the treatment period. The present study has validated the diabetic rabbit model for inducing chronic wounds regarding larval therapy and has likewise confirmed the effectiveness of S. magellanica-derived larval therapy as an alternative for curing and healing wounds. PMID- 26546726 TI - Molecular mechanism of fluoroquinolones modulation on corneal fibroblast motility. AB - Topical fluoroquinolones are widely used to prevent ocular infections after ophthalmic surgery. However, they have been shown to affect the corneal cell motility, whose mechanism remains indefinite. The purpose of this study was to investigate how fluoroquinolones affect corneal stromal cell motility. Human corneal fibroblasts (HCFs) were incubated in ciprofloxacin (CIP), levofloxacin (LEV), or moxifloxacin (MOX) at 0, 10, 50, and 100 MUg/ml for up to 3 days. Effect of CIP, LEV, or MOX on HCF migration was monitored using migration assay. HCF viability was determined by WST-1 assay. Expression of focal adhesion kinase (FAK), paxillin (PXN), and their phosphorylated forms were analyzed by immunoblotting. Binding affinity between FAK and PXN was determined by co immunoprecipitation. Our results revealed that CIP and MOX, but not LEV, noticeably retarded HCF migration. HCF proliferation was significantly reduced by CIP (38.2%), LEV (29.5%), and MOX (21.3%), respectively (p = 0.002). CIP and MOX suppressed the phosphorylation of PXN at tyrosines (10.2 +/- 4.3%, p < 0.001; 11.7 +/- 2.4%, p < 0.001, respectively), including tyrosine 118 (33.3 +/- 5.2%, p < 0.001; 34.0 +/- 4.4%, p < 0.001, respectively). CIP and MOX diminished the binding affinity between FAK and PXN (8.2 +/- 1.8%, p < 0.001; 9.0 +/- 4.5%, p < 0.001, respectively). Nevertheless, tyrosine dephosphorylation and FAK dissociation of PXN were not found in LEV-treated HCFs. None of these fluoroquinolones affect phosphorylation of FAK-Y397. We conclude that CIP and MOX, but not LEV, might delay corneal fibroblast migration via interfering with recruitment of PXN to focal adhesions and dephosphorylation of PXN at the tyrosines. PMID- 26546727 TI - In silico and experimental validation of protein-protein interactions between PknI and Rv2159c from Mycobacterium tuberculosis. AB - Protein-protein interactions control the diverse and essential molecular processes inside the cell. To maintain the cellular physiology, protein kinases not only signal their substrates through reversible phosphorylation, but they also physically interact with them. PknI, a serine/threonine protein kinase of Mycobacterium tuberculosis is known to be important for cellular homoeostasis. In this study, we have identified the interacting proteins for PknI. We screened for proteins interacting with PknI using an in vitro assay, Far-western blot. This protein kinase specifically interacts with two peroxidase proteins of M. tuberculosis, Rv2159c and Rv0148. The PknI-Rv2159c interaction pair was further studied for the critical amino acid residues in Rv2159c that are responsible for the interaction. Rv2159c, a hypothetical protein is predicted to be an antioxidant with peroxidase activity. We performed homology modelling of Rv2159c protein and molecular docking using multiple docking servers such as Z-Dock and ClusPro. Further, the most favorable conformation of PknI-Rv2159c interaction was obtained using molecular dynamics simulation. The critical amino acid residues of the Rv2159c involved in interaction with PknI were identified. Mutation and docking analysis showed that the Ala1-Gly2-Trp3 residues in Rv2159c structure are responsible for the interaction. The free binding energy between the wild type and mutant complexes using MM-GBSA has provided insight about the stability of PknI-Rv2159c interaction. We propose that, PknI physically interacts with Rv2159c both in vitro and in silico studies. PMID- 26546728 TI - Insight into the relationship between structure and magnetic properties in icosahedral FenPt55-n (n=0-55) nanoparticles: DFT approach. AB - Structural, electronic and magnetic properties of FenPt55-n nanoparticles have been systematically studied based on the density functional theory. Firstly, the results show that surface Fe fraction has the same change tendency with excess energy and the nanoparticles have high stability when surface Fe fraction is small and excess energy is low. Secondly, analysis of Bader charge illustrates that the charge transfer reaches the maximum with Pt/Fe atomic ratio of 1:1. Thirdly, total magnetic moments of FenPt55-n nanoparticles increase with the increasing of Fe composition. Pt atom at the center site has promotion effect on the total magnetic moments of FenPt55-n nanoparticles, while Pt atom at the sublayer or outmost layer has inhibition effect. For the atomic magnetic moment, Fe atom occupying the edge of vertex in the second shell site (the center site) has maximum (minimum) atomic magnetic moment. PMID- 26546729 TI - Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung. AB - Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere(r)) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere(r) positive contrast agent for the in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. PMID- 26546730 TI - Biowire platform for maturation of human pluripotent stem cell-derived cardiomyocytes. AB - Human pluripotent stem cells (hPSCs)-derived cardiomyocytes (hPSC-CMs) represent a potential indefinite cell supply for cardiac tissue engineering and possibly regenerative medicine applications. However, these cells are immature compared with adult ventricular cardiomyocytes. In order to overcome this limitation, an engineered platform, called biowire, was devised to provide cultured cardiomyocytes important biomimetic cues present during embryo development, such as three-dimensional cell culture, extracellular matrix composition, soluble factors and pacing through electrical stimulation, to induce the maturation of hPSC-CMs in vitro. PMID- 26546731 TI - Exploration of rice pistil responses during early post-pollination through a combined proteomic and transcriptomic analysis. AB - Pollen-stigma interaction is a multi-step and complex physiological process which contains different signaling and biochemical pathways. However, little is known about the molecular mechanism underlying this process in rice (Oryza sativa). In this study, the changes of gene expression were investigated through a combination study of transcriptome and proteome profiles in rice pistil during pollination. Totally, 1117 differentially expressed genes were identified, among which 962 and 167 were detected at transcriptional and protein level respectively. Functional categorization analysis showed that the genes involved in central metabolism were up-regulated, which can lead to the enhancement of these metabolisms. The reactive oxygen species (ROS) were over-accumulated in the stigma. In response to this, the proteins or transcripts involved in redox homeostasis regulation were differentially expressed. Furthermore, significant changes of protein ubiquitination and its related genes or proteins, especially some E3 ligases encoding genes, indicate that protein ubiquitination might play important roles in cell signal transduction during the pollination process. Our study sheds some lights on gene and protein expression profiles of rice pistil pollination process, and gives us a comprehensive understanding of the basic molecular mechanisms controlling pollination in rice. BIOLOGICAL SIGNIFICANCE: Using RNA-seq, 2-DE and iTRAQ assays, we have generated the large-scale transcriptomic and proteomic data containing abundant information on genes involved in pollen and pistil interaction. Our results showed that ROS were significantly accumulated in stigma after pollination, and the abundance of genes involve in redox homeostasis system were changed variously. We also show that, changes of some E3 ligases encoding genes might indicate that protein ubiquitination play important roles in cell signal transduction during the pollination process. Data in this study might be helpful to deeply understand the pollination in rice. PMID- 26546732 TI - Inactivation of Clostridium difficile spores by microwave irradiation. AB - Spores are a potent agent for Clostridium difficile transmission. Therefore, factors inhibiting spores have been of continued interest. In the present study, we investigated the influence of microwave irradiation in addition to conductive heating for C. difficile spore inactivation in aqueous suspension. The spores of 15 C. difficile isolates from different host origins were exposed to conductive heating and microwave irradiation. The complete inhibition of spore viability at 10(7) CFU/ml was encountered following microwave treatment at 800 W for 60 s, but was not observed in the conductive-heated spores at the same time-temperature exposure. The distinct patterns of ultrastructural alterations following microwave and conductive heat treatment were observed and the degree of damages by microwave was in the exposure time-dependent manner. Microwave would therefore be a simple and time-efficient tool to inactivate C. difficile spores, thus reducing the risk of C. difficile transmission. PMID- 26546733 TI - Capsular typing of Streptococcus pneumoniae isolated in an Algerian hospital using a new multiplex PCR-based scheme. AB - We developed a new sequential multiplex-PCR-based typing scheme (MPBTS) for pneumococcal capsular classification. The serogroup/type of 37 control isolates obtained by the Quellung reaction, MPBTS, and nucleotide sequencing, were fully concordant. The serogroups/types of 75 invasive isolates determined by MPBTS, presented 100% specificity and 96% sensitivity, when compared with the Quellung reaction. PMID- 26546735 TI - Facial emotion recognition in alcohol and substance use disorders: A meta analysis. AB - People with alcohol and substance use disorders (AUDs/SUDs) show worse facial emotion recognition (FER) than controls, though magnitude and potential moderators remain unknown. The aim of this meta-analysis was to estimate the association between AUDs, SUDs and FER impairment. Electronic databases were searched through April 2015. Pooled analyses were based on standardized mean differences between index and control groups with 95% confidence intervals, weighting each study with random effects inverse variance models. Risk of publication bias and role of potential moderators, including task type, were explored. Nineteen of 70 studies assessed for eligibility met the inclusion criteria, comprising 1352 individuals, of whom 714 (53%) had AUDs or SUDs. The association between substance related disorders and FER performance showed an effect size of -0.67 (-0.95, -0.39), and -0.65 (-0.93, -0.37) for AUDs and SUDs, respectively. There was no publication bias and subgroup and sensitivity analyses based on potential moderators confirmed core results. Future longitudinal research should confirm these findings, clarifying the role of specific clinical issues of AUDs and SUDs. PMID- 26546737 TI - Cross protection between the first and second waves of the 1918 influenza pandemic among soldiers of the Canadian Expeditionary Force (CEF) in Ontario. AB - OBJECTIVES: This research analyses morbidity and mortality during the 1918 influenza pandemic among Ontario soldiers in the Canadian Expeditionary Force (CEF). This paper asks: did exposure to influenza during the first wave confer protection against illness and death during the second wave of the pandemic? METHODS: Pneumonia and influenza (P&I) cases and deaths among Ontario soldiers were transcribed from the 1918 Admission and Discharge books for the CEF. Following the methods of Barry et al. [10], hospital admission and mortality rates for P&I were compared for new recruits (<1 month service) and seasoned soldiers (>1 month service) in order to assess the possibility of cross protection during successive waves of the pandemic. RESULTS: The first wave of the 1918 influenza pandemic occurred between March and May of 1918, with the second wave erupting from September to December. Mortality in the second wave was more severe, with a case fatality rate of 4.7%, which was more than double the rate of 2.3% from March to May. Seasoned soldiers experienced 82.5% protection from illness due to P&I illness in the fall, and 84% protection from death. CONCLUSIONS: The morbidity data for the soldier population of Ontario, data unavailable for civilians, confirms the presence of a herald wave in Ontario. The findings support the hypothesis that exposure to influenza during the first wave of the pandemic had a protective effect during the second more deadly wave in the fall. Regional heterogeneity characterized the pandemic among soldiers in Ontario. Conscription practices may have funnelled vulnerable recruits, such as rural farmers, into training camps after the first wave of the pandemic, but prior to the second wave. PMID- 26546734 TI - The interactions of multisensory integration with endogenous and exogenous attention. AB - Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID- 26546736 TI - Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag pol-nef antigen. AB - Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene. PMID- 26546738 TI - Superior protection elicited by live-attenuated vaccines in the murine model of paratuberculosis. AB - Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) causes Johne's disease, a chronic enteric infection in ruminants with severe economic impact on the dairy industry in the USA and worldwide. Currently, available vaccines have limited protective efficacy against disease progression and does not prevent spread of the infection among animals. Because of their ability to elicit wide-spectrum immune responses, we adopted a live-attenuated vaccine approach based on a sigH knock-out strain of M. paratuberculosis (DeltasigH). Earlier analysis of the DeltasigH mutant in mice indicated their inadequate ability to colonize host tissues, unlike the isogenic wild-type strain, validating the role of this sigma factor in M. paratuberculosis virulence. In the present study, we evaluated the performance of the DeltasigH mutant compared to inactivated vaccine constructs in a vaccine/challenge model of murine paratuberculosis. The presented analysis indicated that DeltasigH mutant with or without QuilA adjuvant is capable of eliciting strong immune responses (such as interferon gamma-gamma, IFN-gamma) suggesting their immunogenicity and ability to potentially initiate effective vaccine-induced immunity. Following a challenge with virulent strains of M. paratuberculosis, DeltasigH conferred protective immunity as indicated by the reduced bacterial burden accompanied with reduced lesions in main body organs (liver, spleen and intestine) usually infected with M. paratuberculosis. More importantly, our data indicated better ability of the DeltasigH vaccine to confer protection compared to the inactivated vaccine constructs even with the presence of oil-adjuvant. Overall, our approach provides a rational basis for using live-attenuated mutant strains to develop improved vaccines that elicit robust immunity against this chronic infection. PMID- 26546740 TI - Trans-3,4-dideoxyglucone-3-ene (trans-3,4-DGE), a most reactive glucose degradation product in freshly heat sterilized glucose solutions. AB - In our study, one or more glucose degradation products (GDPs) in freshly heat sterilized dextrose 5% in water (D5W) were found to react with a drug candidate having a beta-keto amide group (Compound A) to form several drug related compounds with the same molecular weight. However the previously identified GDPs did not react with Compound A to produce the observed adducts, indicating that unidentified GDP(s) reacted with Compound A to form these adducts. Our investigation by reaction-directed fractionation of the reactive D5W with HPLC led to the identification of the reactive GDP, trans-3,4-dideoxyglucosone-3-ene (trans-3,4-DGE), responsible for producing these reaction products. The trans-3,4 DGE was identified from its derivatives of dinitrophenylhydrazine (DNPH) and acetoacetanilide and confirmed by (1) admixing Compound A with authentic trans 3,4-DGE to produce the identical impurities as admixing with freshly heat sterilized D5W, and (2) NMR analysis of the reactive fraction of glucose solutions. PMID- 26546741 TI - Recognition of facial expressions of emotion by adults with intellectual disability: Is there evidence for the emotion specificity hypothesis? AB - This study aimed to evaluate the emotion recognition abilities of adults (n=23) with an intellectual disability (ID) compared with a control group of children (n=23) without ID matched for estimated cognitive ability. The study examined the impact of: task paradigm, stimulus type and preferred processing style (global/local) on accuracy. We found that, after controlling for estimated cognitive ability, the control group performed significantly better than the individuals with ID. This provides some support for the emotion specificity hypothesis. Having a more local processing style did not significantly mediate the relation between having ID and emotion recognition, but did significantly predict emotion recognition ability after controlling for group. This suggests that processing style is related to emotion recognition independently of having ID. The availability of contextual information improved emotion recognition for people with ID when compared with line drawing stimuli, and identifying a target emotion from a choice of two was relatively easier for individuals with ID, compared with the other task paradigms. The results of the study are considered in the context of current theories of emotion recognition deficits in individuals with ID. PMID- 26546739 TI - A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition. AB - The TERT gene encodes for the reverse transcriptase activity of the telomerase complex and mutations in TERT can lead to dysfunctional telomerase activity resulting in diseases such as dyskeratosis congenita (DKC). Here, we describe a novel TERT mutation at position T1129P leading to DKC with progressive bone marrow (BM) failure in homozygous members of a consanguineous family. BM hematopoietic stem cells (HSCs) of an affected family member were 300-fold reduced associated with a significantly impaired colony forming capacity in vitro and impaired repopulation activity in mouse xenografts. Recent data in yeast suggested improved cellular checkpoint controls by mTOR inhibition preventing cells with short telomeres or DNA damage from dividing. To evaluate a potential therapeutic option for the patient, we treated her primary skin fibroblasts and BM HSCs with the mTOR inhibitor rapamycin. This led to prolonged survival and decreased levels of senescence in T1129P mutant fibroblasts. In contrast, the impaired HSC function could not be improved by mTOR inhibition, as colony forming capacity and multilineage engraftment potential in xenotransplanted mice remained severely impaired. Thus, rapamycin treatment did not rescue the compromised stem cell function of TERTT1129P mutant patient HSCs and outlines limitations of a potential DKC therapy based on rapamycin. PMID- 26546742 TI - MicroRNA-7: A miRNA with expanding roles in development and disease. AB - MicroRNAs (miRNAs) are a family of short, non-coding RNA molecules (~22nt) involved in post-transcriptional control of gene expression. They act via base pairing with mRNA transcripts that harbour target sequences, resulting in accelerated mRNA decay and/or translational attenuation. Given miRNAs mediate the expression of molecules involved in many aspects of normal cell development and functioning, it is not surprising that aberrant miRNA expression is closely associated with many human diseases. Their pivotal role in driving a range of normal cellular physiology as well as pathological processes has established miRNAs as potential therapeutics, as well as potential diagnostic and prognostic tools in human health. MicroRNA-7 (miR-7) is a highly conserved miRNA which displays restricted spatiotemporal expression during development and in maturity. In humans and mice, mature miR-7 is generated from three different genes, illustrating unexpected redundancy and also the importance of this miRNA in regulating key cellular processes. In this review we examine the expanding role of miR-7 in the context of health, with emphasis on organ differentiation and development, as well as in various mammalian diseases, particularly of the brain, heart, endocrine pancreas and skin, as well as in cancer. The more we learn about miR-7, the more we realise the complexity of its regulation and potential functional application both from a biomarker and therapeutic perspective. PMID- 26546743 TI - Arginine deprivation induces endoplasmic reticulum stress in human solid cancer cells. AB - Deprivation for the single amino acid arginine is a rapidly developing metabolic anticancer therapy, which allows growth control in a number of highly malignant tumors. Here we report that one of the responses of human solid cancer cells to arginine starvation is the induction of prolonged endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Systematic study of two colorectal carcinoma HCT-116 and HT29, glioblastoma U251 MG and ovarian carcinoma SKOV3 cell lines revealed, however, that the ER stress triggered by the absence of arginine does not result in massive apoptosis despite a profound upregulation of the proapoptotic gene CHOP. Instead, Akt- and MAPK-dependent pathways were activated which may counteract proapoptotic signaling. Treatment with DMSO as a disaggregating agent or with cycloheximide to block protein synthesis reduced ER stress evoked by arginine deprivation. On the other hand, ER stress and apoptosis induction in arginine-starved cells could be critically augmented by the arginine analog of plant origin canavanine, but not by the classic ER stress inducer tunicamycin. Our data suggest that canavanine treatment applied under the lack of arginine may enhance the efficacy of arginine deprivation-based anticancer therapy. PMID- 26546744 TI - miR-17 is involved in Japanese Flounder (Paralichthys olivaceus) development by targeting the Cdc42 mRNA. AB - The expression patterns of 197 miRNAs during Japanese flounder metamorphic development were recently analyzed. miR-17 was differentially expressed during the metamorphic period of the Japanese flounder; however, the role of miR-17 in Japanese flounder development has remained elusive to date. Bioinformatics analysis showed that Cdc42 was a putative target of miR-17. Cdc42 is a gene related to cell adhesion, migration, polarity, cytokinesis, growth, actin cytoskeleton, microtubule dynamics and transcription factor activity; thus, Cdc42 may contribute to metamorphic development. In our study, overexpression of miR-17 in FEC cells suppressed Cdc42 expression. The luciferase reporter assay confirmed that Cdc42 was the target of miR-17. The Cdc42 cDNA from the Japanese flounder was cloned and characterized for the first time. The expression of miR-17 was found to be negatively correlated with Cdc42 mRNA expression during temporal development and in the tissues of adult Japanese flounders. These results indicated that the decrease in miR-17 contributed to the up-regulation of Cdc42 during Japanese flounder metamorphosis. Cdc42 gene expression was down-regulated by thyroid hormone during Japanese flounder metamorphosis, whereas miR-17 was significantly up-regulated by thyroid hormone during these stages. These results indicated that miR-17 was a negative regulator of Cdc42. PMID- 26546745 TI - Activation of RXR/PPARgamma underlies neuroprotection by bexarotene in ischemic stroke. AB - The identification of novel drug targets for the treatment of ischemic stroke is currently an urgent challenge. Recent experimental findings have highlighted the neuroprotective potential of immunomodulatory strategies, based on polarization of myeloid cells toward non-inflammatory, beneficial phenotypes. Given the role of retinoid X receptors (RXR) in myeloid cells differentiation and polarization, here we have explored the neuroprotective potential of the RXR agonist bexarotene in mice subjected to focal cerebral ischemia. Acute administration of bexarotene significantly reduced blood brain barrier leakage, brain infarct damage and neurological deficit produced by transient middle cerebral artery occlusion in mice, without affecting cerebral blood flow. The rexinoid exerted neuroprotection with a wide time-window, being effective when administered up to 4.5h after the insult. The amelioration of histological outcome, as well as the ability of bexarotene to revert middle cerebral artery occlusion (MCAo)-induced spleen atrophy, was antagonised by BR1211, a pan-RXR antagonist, or by the selective peroxisome proliferator-activated receptor (PPAR)gamma antagonist bisphenol A diglycidyl ether (BADGE), highlighting the involvement of the RXR/PPARgamma heterodimer in the beneficial effects exerted by the drug. Immunofluorescence analysis revealed that bexarotene elevates Ym1-immunopositive N2 neutrophils both in the ipsilateral hemisphere and in the spleen of mice subjected to transient middle cerebral artery occlusion, pointing to a major role for peripheral neutrophil polarization in neuroprotection. Thus, our findings suggest that the RXR agonist bexarotene exerts peripheral immunomodulatory effects under ischemic conditions to be effectively repurposed for the acute therapy of ischemic stroke. PMID- 26546746 TI - Aclidinium bromide combined with formoterol inhibits remodeling parameters in lung epithelial cells through cAMP. AB - Combined muscarinic receptor antagonists and long acting beta2-agonists improve symptom control in chronic obstructive pulmonary disease (COPD) significantly. In clinical studies aclidinium bromide achieved better beneficial effects than other bronchodilators; however, the underlying molecular mechanisms are unknown. This study assessed the effect of aclidinium bromide combined with formoterol on COPD lung (n=20) and non-COPD lung (n=10) derived epithelial cells stimulated with TGF beta1+carbachol on: (i) the generation of mesenchymal cells in relation to epithelial cells, (II) extracellular matrix (ECM) deposition, and (iii) the interaction of ECM on the generation of epithelial and mesenchymal cells. TGF beta1+carbachol enhanced the generation of mesenchymal cells, which was significantly reduced by aclidinium bromide or formoterol. The effect of combined drugs was additive. Inhibition of p38 MAP kinase and Smad by specific inhibitors or aclidinium bromide reduced the generation of mesenchymal cells. In mesenchymal cells, TGF-beta1+carbachol induced the deposition of collagen-I and fibronectin which was prevented by both drugs dose-dependently. Formoterol alone reduced collagen-I deposition via cAMP, this however, was overruled by TGF beta1+carbachol and rescued by aclidinium bromide. Inhibition of fibronectin was cAMP independent, but involved p38 MAP kinase and Smad. Seeding epithelial cells on ECM collagen-I and fibronectin induced mesenchymal cell generation, which was reduced by aclidinium bromide and formoterol. Our results suggest that the beneficial effect of aclidinium bromide and formoterol involves cAMP affecting both, the accumulation of mesenchymal cells and ECM remodeling, which may explain the beneficial effect of the drugs on lung function in COPD. PMID- 26546747 TI - Cholinergic transmission underlies modulation of frustration by open field exposure. AB - Frustration can be defined as an emotional state generated by the omission or devaluation in the quantity or quality of an expected appetitive reward. Thus, reactivity to a reward is affected by prior experience with the different reinforcer values of that reward. This phenomenon is known as incentive relativity, and can be studied by different paradigms. Although methodologically simple, the exploration of a novel open field (OF) is a complex situation that involves several behavioral processes, including stress induction and novelty detection. OF exposure can enhance or block the acquisition of associative and non-associative memories. These experiments evaluated the effect of OF exploration on frustration and the role played by the cholinergic system in this phenomenon. OF exploration before first or second trial of incentive downshift modulated the expression of frustration. This effect of OF was blocked by the administration of scopolamine either before or after OF exploration. These results indicate that the cholinergic system is involved in the acquisition and consolidation of OF information. PMID- 26546748 TI - p-Methoxycinnamic acid, an active phenylpropanoid induces mitochondrial mediated apoptosis in HCT-116 human colon adenocarcinoma cell line. AB - Among the eight phytochemicals (dihydrocarveol, sinapic acid, vanillic acid, ethylgallate, myrtenol, transcarveol, p-methoxycinnamic acid, and isoferulic acid) we tested, p-methoxycinnamic acid (p-MCA) [10 MUM] showed the most potent in vitro growth inhibition on human colon adenocarcinoma (HCT-116 cells). Antiproliferative activity of p-MCA at 24h was associated with DNA damage, morphological changes and the results were comparable with doxorubicin. p-MCA induced phosphatidylserine translocation, increased the levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and decreased enzymic antioxidant status (SOD, CAT, GPx) in HCT 116. p-MCA treatment increased the percentage of apoptotic cells, decreased the mitochondrial membrane potential and triggered cytochrome C release to cytosol. The induction of apoptosis by p-MCA was accompanied by an increase in caspase 3 and caspase 9 activities, increased expression of Bax and decreased expression of Bcl-2. Thus p-MCA induces mitochondria mediated intrinsic pathway of apoptosis in HCT-116 and has potential for treatment and prevention of colon cancer. PMID- 26546749 TI - Hematopoiesis "awakens": Evolving technologies, the force behind them. AB - Amid the beauty of the Kyoto countryside, leaders in the field of hematology met at the 44th annual International Society for Experimental Hematology (ISEH) meeting in late September 2015. Led by ISEH President Paul Frenette and President Elect David Traver, the meeting covered many aspects of hematopoiesis with a focus on technology. At the meeting, it became clear that the future of hematology is being shaped by innovations in single-cell "omics" and imaging approaches that will provide answers to age-old questions on cellular identity. In this meeting review, we highlight the advances presented in understanding the hematopoietic stem cell (HSC) niche, heterogeneity, stress response, epigenetics, and how these processes change from birth to old age. PMID- 26546750 TI - Impact of subsequent screening episodes on the positive predictive value for advanced neoplasia and on the distribution of anatomic subsites of colorectal cancer: A population-based study on behalf of the French colorectal cancer screening program. AB - BACKGROUND: The anatomic distribution of advanced colorectal neoplasia is increasingly important for choosing screening strategies and treatment options. We sought to evaluate the impact of repeated screening on the positive predictive value (PPV) for advanced colorectal neoplasia (advanced adenoma, AA, and colorectal cancer, CRC) and their distribution according to anatomic subsite distribution in average-risk adults. METHOD: The study included 98,031 men and women aged 50-74 who had a positive g-FOBT in 2010 and 2011 and underwent total colonoscopy. The PPV for detection of AA and CRC and the relative risks were determined with log-binomial models, and the distribution of anatomic subsites was estimated according to screening history. RESULT: The median age was 61 years (62 years for participants with AA and 64 for those with CRC). The PPV for detection of advanced neoplasia was 24.5%, substantially higher in men than women (30.7% vs 17.7%), and it increased with age. It also fell at all screening episodes after the first. Subsequent screening episodes were associated with an increased RR for proximal AA (RR 1.13, 95% CI 1.16-1.20). Advancing age (RR 1.28, 95% CI 1.19-1.39 for every 10-year increase in age), female gender (RR 1.31, 95% CI 1.19-1.44), and subsequent screening (RR 1.15, 95% CI 1.04-1.27) were significantly and independently associated with detection of proximal adenocarcinoma. The latter was also detected at an advanced stage more often (RR, 1.24, 95% CI: 1.09-1.42). Early stages of invasive adenocarcinoma (stages I and II) was more likely to be detected in a subsequent than an initial screening (RR 1.07, 95% CI 1.01-1.13). CONCLUSION: This study found that subsequent screening episodes using g-FOBT were associated with an increase in the detection rate of proximal AA and CRC, especially among women. The more frequent detection of proximal invasive adenocarcinoma at an advanced stage in subsequent screenings suggests that some of these tumors may well not be real incident lesions, but are likely to include lesions that were missed on the previous screens. Although modest, the increase in the rate of detection of invasive adenocarcinoma at early (and more curable) stages from the first to subsequent screenings, together with this potential for missed diagnoses on initial screening and the increased detection rate for proximal or rectal AA in subsequent screening episodes, underlines the need to reinforce the population's awareness of the importance of regular consistent screening, after negative results. PMID- 26546752 TI - The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-kappaB) pathway by targeting RelA/p65. AB - Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the following statements: (i) ART exerts antiviral activity towards human and animal herpesviruses, (ii) no induction of ART-resistant HCMV mutants occurred in vitro, (iii) chemically modified derivatives of ART showed strongly enhanced anti-HCMV efficacy, (iv) NF-kappaB reporter constructs, upregulated during HCMV replication, could be partially blocked by ART treatment, (v) ART activity analyzed in stable reporter cell clones indicated an inhibition of stimulated NF kappaB but not CREB pathway, (vi) solid-phase immobilized ART was able to bind to NF-kappaB RelA/p65, and (vii) peptides within NF-kappaB RelA/p65 represent candidates of ART binding as analyzed by in silico docking and mass spectrometry. These novel findings open new prospects for the future medical use of ART and ART related drug candidates. PMID- 26546753 TI - A Rare Cause of Malabsorption. PMID- 26546754 TI - Achalasia: All Sticks in One Bundle! PMID- 26546755 TI - Clinical indicators associated with the mode of twin delivery: an analysis of 22,712 twin pairs. AB - OBJECTIVE: To identify clinical indicators associated with the planned and actual mode of delivery in women with a twin pregnancy. STUDY DESIGN: We performed a retrospective cohort study in women with a twin pregnancy who delivered at a gestational age of 32+0-41+0 weeks and days between 2000 and 2008 in the Netherlands. Data were obtained from a nationwide database. We identified maternal, pregnancy-related, fetal, neonatal and hospital-related indicators that were associated with planned cesarean section (CS) and, for women with planned vaginal delivery (VD), for intrapartum CS. The associations between indicators and mode of delivery were studied with uni- and multivariate logistic regression analyses. RESULTS: We included 22,712 women with a twin pregnancy, of whom 4,310 women (19.0%) had a planned CS. Of the 18,402 women who had a planned VD, 14,034 (76.3%) delivered vaginally, 3,545 (19.3%) had an intrapartum CS, while 823 (4.5%) delivered twin A vaginally and twin B by intrapartum CS. The clinical indicators for a planned CS and an intrapartum CS were comparable: non-cephalic position of both twins (aOR 25.32; 95% CI 22.50-28.50, and aOR 21.94; 95% CI 18.67-25.78, respectively), non-cephalic position of twin A only (aOR 21.67 95% CI 19.12-24.34, and aOR 13.71; 95% CI 11.75-16.00, respectively), previous CS (aOR 3.69; 95% CI 3.12-4.36, and aOR 7.00; 95% CI 5.77-8.49, respectively), nulliparity (aOR 1.51; 95% CI 1.32-1.72, and aOR 4.20; 95% CI 3.67-4.81, respectively), maternal age >=41 years (aOR 3.00; 95% CI 2.14-4.22, and aOR 2.50; 95% CI 1.75-3.59, respectively), and pre-eclampsia (aOR 2.12; 95% CI 1.83-2.46, and aOR 1.34; 95% CI 1.16-1.56, respectively). CONCLUSION: Both planned and intrapartum CS in twins had comparable predictors: non-cephalic position of both twins or twin A only, previous CS, nulliparity, advanced maternal age, and pre eclampsia. PMID- 26546751 TI - Recent advances of cocktail chemotherapy by combination drug delivery systems. AB - Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID- 26546756 TI - The impact of GnRH agonists in patients with endometriosis on prolactin and sex hormone levels: a pilot study. AB - OBJECTIVE: Gonadotropin releasing hormone agonists (GnRHa) decrease the expression of growth factors involved in the development of human endometriotic tissue. As endometriosis has been found to be associated with a mild increase in prolactin (PRL) serum levels, we aimed to evaluate changes in PRL serum levels as well as other hormones relevant to endometriosis and infertility during long-term administration of GnRHas in women with endometriosis. STUDY DESIGN: In this prospective pilot study we obtained blood samples on the first day of leuporeline administration and then subsequently after 4, 8 and 12 weeks in 22 patients. RESULTS: Median PRL levels were unchanged after 4 weeks, but significantly decreased 8 and 12 weeks after the first leuporeline administration (p1=0.085, p2=0.020, p3=0.001). There was no significant decrease in serum anti-Mullerian hormone (AMH) levels over the whole period of down regulation with leuporeline (p1-3>0.05). CONCLUSION: Our data support the hypothesis that the decrease of PRL levels might contribute to the known effect of GnRH treatment in patients with endometriosis via suppression of VEGF expression in endometriotic lesions. Moreover this study lends support to the thesis that AMH remains stable under GnRHa therapy and therefore can be also used as a marker of ovarian function prior to IVF-stimulation during down regulation. PMID- 26546757 TI - Prediction models for successful external cephalic version: a systematic review. AB - To provide an overview of existing prediction models for successful ECV, and to assess their quality, development and performance. We searched MEDLINE, EMBASE and the Cochrane Library to identify all articles reporting on prediction models for successful ECV published from inception to January 2015. We extracted information on study design, sample size, model-building strategies and validation. We evaluated the phases of model development and summarized their performance in terms of discrimination, calibration and clinical usefulness. We collected different predictor variables together with their defined significance, in order to identify important predictor variables for successful ECV. We identified eight articles reporting on seven prediction models. All models were subjected to internal validation. Only one model was also validated in an external cohort. Two prediction models had a low overall risk of bias, of which only one showed promising predictive performance at internal validation. This model also completed the phase of external validation. For none of the models their impact on clinical practice was evaluated. The most important predictor variables for successful ECV described in the selected articles were parity, placental location, breech engagement and the fetal head being palpable. One model was assessed using discrimination and calibration using internal (AUC 0.71) and external validation (AUC 0.64), while two other models were assessed with discrimination and calibration, respectively. We found one prediction model for breech presentation that was validated in an external cohort and had acceptable predictive performance. This model should be used to council women considering ECV. PMID- 26546758 TI - New insights into the transformation of trimethoprim during biological wastewater treatment. AB - The antibiotic trimethoprim (TMP), a micropollutant found at MUg/L levels in raw wastewater, was investigated with regard to its (bio)transformation during biological wastewater treatment. A pilot-scale, nitrifying/denitrifying Sequencing Batch Reactor (SBR) fed with municipal wastewater was monitored for TMP removal during a 16-month monitoring study. Laboratory-scaled bioreactors spiked with TMP were applied to identify the transformation products (TPs). In total, six TPs could be identified from TMP. However, the TP formation was influenced by the spike concentration. At an initial concentration of 500 MUg/L TMP, only two TPs were found, whereas at 5 MUg/L a completely different transformation pathway led to four further TPs. At low concentrations, TMP was demethylated forming 4-desmethyl-TMP, which was then quickly hydroxylated, oxidized and cleaved forming 2,4-diaminopyrimidine-5-carboxylic acid (DAPC) via two intermediate TPs. DAPC was detected in the SBR effluent in a 3-d composite sample with 61 ng/L, which accounts for 52% of the attenuated TMP. The primary degradation at low spiking levels was best modelled by a pseudo-first order kinetic. Considering the SBR, the model predicted a TMP removal of 88-94% for the reactor, consistent with a monitoring campaign exhibiting an average removal of >83%. Both the TP formation profiles and kinetic modelling indicated that only the results from the bioreactor tests at low spike concentrations were representative of the transformation in the SBR. PMID- 26546759 TI - Simulation of saxitoxins adsorption in full-scale GAC filter using HSDM. AB - Many different species of cyanobacteria capable of producing saxitoxins have been identified as a threat to the safety of drinking water supplies worldwide. Removal of these contaminants can be accomplished by adsorption on granular activated carbon (GAC) but little is yet known about the kinetics of this process. This research investigated adsorption kinetics and diffusion behaviour of decarbomoyl saxitoxin (dc-STX) and carbamate saxitoxin (STX) on a GAC sample and simulated a full-scale GAC filter using batch experimental data and the homogeneous surface diffusion model (HSDM). HSDM was able to successfully describe batch adsorption of STX and dc-STX onto GAC sample and the surface diffusion coefficient was identified as the main adjustment parameter for this model. Different scenarios of STX and dc-STX removal in a GAC filter were simulated, offering engineers and scientists an option for the design of GAC full scale filters, bench or pilot-scale experiments. PMID- 26546760 TI - Water management impacts on arsenic behavior and rhizosphere bacterial communities and activities in a rice agro-ecosystem. AB - Although rice cultivated under water-saturated conditions as opposed to submerged conditions has received considerable attention with regard to reducing As levels in rice grain, the rhizosphere microbiome potentially influencing As biotransformation and bioavailability in a rice ecosystem has rarely been studied. In this study, the impacts of flooded, non-flooded and alternate wetting and drying (AWD) practices on rhizosphere bacterial composition and activities that could potentially impact As speciation and accumulation in rhizosphere soil and pore water, As fractions in rhizosphere soil and As speciation and distribution in plant parts were assessed. The results revealed that in addition to pore water As concentration, non-specifically sorbed As fraction, specifically sorbed As fraction and amorphous iron oxide bound As fraction in soil were bio available to rice plants. In the flooded treatment, As(III) in the pore water was the predominant As species, accounting for 87.3-93.6% of the total As, whereas in the non-flooded and AWD treatments, As(V) was the dominant As species, accounting for 89.6-96.2% and 73.0-83.0%, respectively. The genera Ohtaekwangia, Geobacter, Anaeromyxobacter, Desulfuromonas, Desulfocapsa, Desulfobulbus, and Lacibacter were found in relatively high abundance in the flooded soil, whereas the genera Acinetobacter, Ignavibacterium, Thiobacillus, and Lysobacter were detected in relatively high abundance in the non-flooded soil. Admittedly, the decrease in As level in rice cultivated under the non-flooded and AWD conditions was mostly linked to a relatively high soil redox potential, low As(III) concentration in the soil pore water, a decrease in the relative abundance of As-, Fe- and sulfur reducing bacteria and an increase in the relative abundance of As-, Fe- and sulfur-oxidizing bacteria in the rhizosphere soil of the rice. This study demonstrated that with substantial reduction in grain As levels and higher water productivity, AWD practice in rice cultivation should be favored over the non flooded and continuously flooded rice cultivations in As-contaminated sites. PMID- 26546761 TI - Evaluation of serum markers of blood redox homeostasis and inflammation in PCB naturally contaminated heifers undergoing decontamination. AB - Dioxins and polychlorinated biphenyls (PCBs) are widely spread and long persistent contaminants. The aim of this study was to evaluate physiological changes associated with the decontamination of animals previously exposed to environmental pollutants. Eight Limousine heifers were removed from a polluted area and fed a standard ration for six months. The extent of contamination was defined by measuring total toxic equivalents (TEQ) values of dioxin like-PCBs (DL PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs), and NDL-PCBs amount in pericaudal fat two weeks after the removal from the contaminated area (day 0) and then bimonthly for six months during the decontamination (days 59, 125, and 188). The concentrations of both DL PCBs + PCDD/Fs and NDL-PCBs at the start of decontamination (day 0) were higher than those legally admitted, and they were strongly decreased at the end of the experimental period. Specific indices of blood redox homeostasis and inflammation were also measured at each time. Serum concentrations of Retinol, Tocopherol and Ascorbate, the total antioxidant capacity (TAC) and the activities of superoxide dismutase and glutathione peroxidase were lower at day 0 than after 59, 125 or 188 days of decontamination. Protein-bound carbonyls (PC), nitro-tyrosine (N Tyr), and lipid hydroperoxides concentrations were higher at day 0 than during decontamination. In addition, TAC, PC and N-Tyr levels correlated with both DL PCB and NDL-PCB concentrations only at day 0. Serum concentrations of TNF-alpha and Haptoglobin were higher in samples collected at day 0 than in those obtained during decontamination. As Haptoglobin and TNF-alpha levels correlated with both DL-PCB and NDL-PCB concentrations at day 0 and at day 59 (when these concentrations are still over legal limit), they might represent easily measurable parameters for assessing acute exposure to pollutants. Further both N Tyr and TNF-alpha concentrations could be used as bio-monitoring markers of the decontamination procedure. PMID- 26546762 TI - Quinolone resistant Aeromonas spp. as carriers and potential tracers of acquired antibiotic resistance in hospital and municipal wastewater. AB - Members of the genus Aeromonas are recognized carriers of antibiotic resistance in aquatic environments. However, their importance on the spread of resistance from hospital effluents to the environment is poorly understood. Quinolone resistant Aeromonas spp. (n = 112) isolated from hospital effluent (HE) and from raw (RWW) and treated wastewater (TWW) of the receiving urban wastewater treatment plant (UWTP) were characterized. Species identification and genetic intraspecies diversity were assessed based on the 16S rRNA, cpn60 and gyrB genes sequence analysis. The antibiotic resistance phenotypes and genotypes (qnrA, qnrB, qnrC, qnrD, qnrS, qnrVC; qepA; oqxAB; aac(6')-Ib-cr; blaOXA; incU) were analyzed in function of the origin and taxonomic group. Most isolates belonged to the species Aeromonas caviae and Aeromonas hydrophila (50% and 41%, respectively). The quinolone and the beta-lactamase resistance genes aac(6')-Ib cr and blaOXA, including gene blaOXA-101, identified for the first time in Aeromonas spp., were detected in 58% and 56% of the isolates, respectively, with identical prevalence in HE and UWTP wastewater. In contrast, the gene qnrS2 was observed mainly in isolates from the UWTP (51%) and rarely in HE isolates (3%), suggesting that its origin is not the clinical setting. Bacterial groups and genes that allow the identification of major routes of antibiotic resistance dissemination are valuable tools to control this problem. In this study, it was concluded that members of the genus Aeromonas harboring the genes aac(6')-Ib-cr and blaOXA are relevant tracers of antibiotic resistance dissemination in wastewater habitats, while those yielding the gene qnrS2 allow the traceability from non-clinical sources. PMID- 26546763 TI - Comparing a silver-impregnated activated carbon with an unmodified activated carbon for disinfection by-product minimisation and precursor removal. AB - During disinfection, bromide, iodide and natural organic matter (NOM) in source waters can lead to the formation of brominated and/or iodinated disinfection by products (DBPs), which are often more toxic than their chlorinated analogues. The objective of this study was to compare the efficiency of a silver-impregnated activated carbon (SIAC) with the equivalent unimpregnated granular activated carbon (GAC) for the removal of bromide, iodide and NOM from a matrix of synthetic waters with variable NOM, halide, and alkalinity concentrations, and to investigate the impact on DBP formation. An enhanced coagulation (EC) pre treatment was employed prior to sample exposure to either carbon adsorbent. Excellent halide removals were observed by the SIAC treatment across the sample matrix, with iodide concentrations consistently reduced to below the method reporting limit (<2 MUg/L) from as high as 25 MUg/L, and 95+/-4% removal of bromide achieved. Bromide removal by unimpregnated GAC was poor, however iodide removal was comparable to that achieved by SIAC. The combination of EC with SIAC treatment removed 77+/-8% of the dissolved organic carbon (DOC) present, across the sample matrix, which was similar to removals by EC/GAC (67+/-14%). Combined EC/SIAC treatment reduced both total trihalomethanes (tTHMs) and total dihaloacetonitriles (tDHANs) formation by 97+/-3%, while also achieving a greater than 74% removal of two chloropropanones and a 92+/-8% decrease in chloral hydrate (CH), compared to untreated samples, regardless of the sample's starting water quality (bromide, alkalinity and NOM concentration). Combined EC/GAC treatment led to similar DBP removals to EC/SIAC for the fully chlorinated DBPs, however, brominated DBPs were less efficiently removed, or experienced concentration increases. PMID- 26546764 TI - Edaphic factors controlling summer (rainy season) greenhouse gas emissions (CO2 and CH4) from semiarid mangrove soils (NE-Brazil). AB - The soil attributes controlling the CO2, and CH4 emissions were assessed in semiarid mangrove soils (NE-Brazil) under different anthropogenic activities. Soil samples were collected from different mangroves under different anthropogenic impacts, e.g., shrimp farming (Jaguaribe River); urban wastes (Coco River) and a control site (Timonha River). The sites were characterized according to the sand content; physicochemical parameters (Eh and pH); total organic C; soil C stock (SCS) and equivalent SCS (SCSEQV); total P and N; dissolved organic C (DOC); and the degree of pyritization (DOP). The CO2 and CH4 fluxes from the soils were assessed using static closed chambers. Higher DOC and SCS and the lowest DOP promote greater CO2 emission. The CH4 flux was only observed at Jaguaribe which presented higher DOP, compared to that found in mangroves from humid tropical climates. Semiarid mangrove soils cannot be characterized as important greenhouse gas sources, compared to humid tropical mangroves. PMID- 26546765 TI - The changing trend in nitrate concentrations in major aquifers due to historical nitrate loading from agricultural land across England and Wales from 1925 to 2150. AB - Nitrate is necessary for agricultural productivity, but can cause considerable problems if released into aquatic systems. Agricultural land is the major source of nitrates in UK groundwater. Due to the long time-lag in the groundwater system, it could take decades for leached nitrate from the soil to discharge into freshwaters. However, this nitrate time-lag has rarely been considered in environmental water management. Against this background, this paper presents an approach to modelling groundwater nitrate at the national scale, to simulate the impacts of historical nitrate loading from agricultural land on the evolution of groundwater nitrate concentrations. An additional process-based component was constructed for the saturated zone of significant aquifers in England and Wales. This uses a simple flow model which requires modelled recharge values, together with published aquifer properties and thickness data. A spatially distributed and temporally variable nitrate input function was also introduced. The sensitivity of parameters was analysed using Monte Carlo simulations. The model was calibrated using national nitrate monitoring data. Time series of annual average nitrate concentrations along with annual spatially distributed nitrate concentration maps from 1925 to 2150 were generated for 28 selected aquifer zones. The results show that 16 aquifer zones have an increasing trend in nitrate concentration, while average nitrate concentrations in the remaining 12 are declining. The results are also indicative of the trend in the flux of groundwater nitrate entering rivers through baseflow. The model thus enables the magnitude and timescale of groundwater nitrate response to be factored into source apportionment tools and to be taken into account alongside current planning of land-management options for reducing nitrate losses. PMID- 26546766 TI - Role of biotransformation, sorption and mineralization of (14)C-labelled sulfamethoxazole under different redox conditions. AB - (14)C-sulfamethoxazole biotransformation, sorption and mineralization was studied with heterotrophic and autotrophic biomass under aerobic and anoxic conditions, as well as with anaerobic biomass. The (14)C-radiolabelled residues distribution in the solid, liquid and gas phases was closely monitored along a total incubation time of 190 h. Biotransformation was the main removal mechanism, mineralization and sorption remaining below 5% in all the cases, although the presence of a carbon source exerted a positive effect on the mineralization rate by the aerobic heterotrophic bacteria. In fact, an influence of the type of primary substrate and the redox potential was observed in all cases on the biotransformation and mineralization rates, since an enhancement of the removal rate was observed when an external carbon source was used as a primary substrate under aerobic conditions, while a negligible effect was observed under nitrifying conditions. In the liquid phases collected from all assays, up to three additional peaks corresponding to (14)C-radiolabelled residues were detected. The highest concentration was observed under anaerobic conditions, where two radioactive metabolites were detected representing each around 15% of the total applied radioactivity after 180 h incubation. One of the metabolites detected under anoxic and anaerobic conditions, is probably resulting from ring cleavage of the isoxazole ring. PMID- 26546767 TI - The influence of rainwater composition on the conservation state of cementitious building materials. AB - Rainwater is one of the main pollution tracers around the world. There are many reasons that can explain the presence of high concentrations of certain hazardous elements (HEs) in the rainwater (traffic, marine port activities, industry, etc.). In this work, rainwater samples were collected at six different locations in the Metropolitan Bilbao (Basque Country, north of Spain) during November 2014. HE concentrations were determined by means of inductively coupled plasma mass spectrometry (ICP-MS) and anions by ion chromatography. The pH and redox potential values on these samples were also assessed. According to the obtained results, different trends along the estuary of Bilbao have been observed. To corroborate some hypothesis, thermodynamic simulations and correlation analyses were also carried out using quantitative data. These trends are closely related to the surrounding pollution and marine influence. Finally, in order to ascertain the influence of the Metropolitan Bilbao rainwater on buildings materials, a recent construction was characterized. Using techniques such as Scanning Electron Microscopy coupled with Energy Dispersive X-Ray Spectroscopy (SEM-EDS) and Raman Spectroscopy, different types of sulfates and nitrates were observed. PMID- 26546768 TI - Toxicity of seven priority hazardous and noxious substances (HNSs) to marine organisms: Current status, knowledge gaps and recommendations for future research. AB - Shipping industry and seaborne trade have rapidly increased over the last fifty years, mainly due to the continuous increasing demand for chemicals and fuels. Consequently, despite current regulations, the occurrence of accidental spills poses an important risk. Hazardous and noxious substances (HNSs) have been raising major concern among environmental managers and scientific community for their heterogeneity, hazardous potential towards aquatic organisms and associated social-economic impacts. A literature review on ecotoxicological hazards to aquatic organisms was conducted for seven HNSs: acrylonitrile, n-butyl acrylate, cyclohexylbenzene, hexane, isononanol, trichloroethylene and xylene. Information on the mechanisms of action of the selected HNS was also reviewed. The main purpose was to identify: i) knowledge gaps in need of being addressed in future research; and ii) a set of possible biomarkers suitable for ecotoxicological assessment and monitoring in both estuarine and marine systems. Main gaps found concern the scarcity of information available on ecotoxicological effects of HNS towards marine species and their poorly understood mode of action in wildlife. Differences were found between the sensitivity of freshwater and seawater organisms, so endpoints produced in the former may not be straightforwardly employed in evaluations for the marine environment. The relationship between sub individual effects and higher level detrimental alterations (e.g. behavioural, morphological, reproductive effects and mortality) are not fully understood. In this context, a set of biomarkers associated to neurotoxicity, detoxification and anti-oxidant defences is suggested as potential indicators of toxic exposure/effects of HNS in marine organisms. Overall, to support the development of contingency plans and the establishment of environmental safety thresholds, it will be necessary to undertake targeted research on HNS ecotoxicity in the marine environment. Research should address these issues under more realistic exposure scenarios reflecting the prevailing spatial and temporal variability in ecological and environmental conditions. PMID- 26546769 TI - Association between greenness, urbanicity, and birth weight. AB - BACKGROUND: More than half of the world's population lives in urban environments. Due to urban related factors (e.g. higher air pollution), urban residents may face higher risk of adverse health outcomes, while access to green space could benefit health. PURPOSE: We explored associations between urban and green land use and birth weight. METHODS: Connecticut, U.S., birth certificate data (2000 2006) were acquired (n=239,811), and land-use data were obtained from the National Land Cover Database. We focused on three land-uses; urban space, urban open space, and green space (i.e. forest, shrub, herbaceous, and cultivated land). We estimated fractions of greenness and urbanicity within 250 m from residence. A linear mixed effects model was conducted for birth weight and a logistic mixed effects model for low birth weight (LBW) and small for gestational age (SGA). RESULTS: An interquartile range (IQR) increment in the fraction of green space within 250 m of residence was associated with 3.2g (95% Confidence Interval [0.4, 6.0]) higher birth weight. Similarly, an IQR increase in green space was associated with 7.6% [2.6, 12.4] decreased risk of LBW. Exposure to urban space was negatively correlated with green space (Pearson correlation= 0.88), and it showed negative association with birth outcomes. Results were generally robust with different buffer sizes and controlling for fine particles (PM2.5) and traffic. CONCLUSIONS: We found protective associations by green space on birth outcomes. Increasing green space and/or reducing urban space (e.g. the greening of city environments) may reduce the risk of adverse birth outcomes such as LBW and SGA. Populations living in urban environments will grow in the next half century, and allocation of green space among urban areas may play a critical role for public health in urban planning. PMID- 26546770 TI - Couple comorbidity and correlates of postnatal depressive symptoms in mothers and fathers in the first two weeks following delivery. AB - BACKGROUND: Postnatal depression affects a significant number of parents; however, its co-occurrence in mothers and fathers has not been studied extensively. Identifying predictors and correlates of postnatal depressive symptoms can help develop effective interventions. METHODS: Questionnaires on several socio-demographic and psychosocial factors were administered to 276 couples within two weeks after birth. Depressive symptoms in mothers and fathers were assessed using the Edinburgh Postnatal Depression Scale (EPDS). After calculating the correlation coefficient between mothers and fathers' EPDS scores, univariate and multivariate linear regression analyses were performed to identify significant correlates of postnatal depressive symptoms in mothers and fathers. RESULTS: Prevalence of maternal and paternal postnatal depressive symptoms was 15.9% (EPDS>12) and 5.4% (EPDS>10), respectively. There was a moderate positive correlation between mothers and fathers' EPDS scores (r=.30, p<.001). Multivariate analyses indicated that parental stress was the strongest predictor for maternal and paternal postnatal depressive symptoms. Pregnancy- and birth related distress and partners' EPDS scores were also associated with depressive symptoms in both parents. Relationship satisfaction was only inversely related with fathers' EPDS scores, while mothers' EPDS scores were additionally associated with critical life events, history of childhood violence, and birth related physiological complaints. LIMITATIONS: Since information about participation rates (those who declined) is unavailable, we cannot rule out sampling bias. Further, some psychosocial factors were assessed using single items. CONCLUSION: Since co-occurrence of depressive symptoms in mothers and fathers is high, developing and evaluating postnatal depression interventions for couples may be beneficial. Interventions to reduce parenting stress may help prevent parental postnatal depression. PMID- 26546771 TI - Inclusion/exclusion criteria in placebo-controlled studies of vortioxetine: Comparison to other antidepressants and implications for product labeling. AB - BACKGROUND: We recently conducted a comprehensive review of the psychiatric inclusion/exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) published during the past 20 years and found that the criteria of more recent studies were significantly more restrictive than prior studies. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). We compared the inclusion/exclusion criteria of the vortioxetine studies to the criteria used in other AETs, and discuss the broader issue of the generalizability of AETs and the implications this might have for the labeling of antidepressants receiving FDA approval. METHODS: We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We identified 170 AETs published during this 20 year period and compared the inclusion/exclusion criteria used in the 12 studies of vortioxetine to those used in the nonvortioxetine studies. A second analysis compared vortioxetine to the 3 antidepressants most recently approved prior to vortioxetine (desvenlafaxine, levomilnacipran extended release, vilazodone). RESULTS: Compared to the nonvortioxetine AETs, the vortioxetine studies significantly more often excluded patients with any comorbid Axis I disorder (p<.001) and more often required the current depressive episode to be longer than the DSM minimum symptom duration requirement of 2 weeks (p<.01). The cutoff on the Montgomery Asberg Depression Rating Scale required for inclusion in the vortioxetine studies was higher than the cutoff used in the other AETs (p<.01). LIMITATIONS: A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants. CONCLUSION: The inclusion/exclusion criteria in the studies of vortioxetine were more restrictive than the criteria used in other AETs. Inconsistent with FDA guidelines on the labeling of medications, the label of vortioxetine does not include a description of the limits to the group of patients with MDD for whom the medication has been shown to be effective. PMID- 26546772 TI - Suicide and the Internet: Changes in the accessibility of suicide-related information between 2007 and 2014. AB - BACKGROUND: Following the ongoing concerns about cyber-suicide, we investigate changes between 2007 and 2014 in material likely to be accessed by suicidal individuals searching for methods of suicide. METHODS: 12 search terms relating to suicide methods were applied to four search engines and the top ten hits from each were categorised and analysed for content. The frequency of each category of site across all searches, using particular search terms and engines, was counted. RESULTS: Key changes: growth of blogs and discussion forums (from 3% of hits, 2007 to 18.5% of hits, 2014); increase in hits linking to general information sites - especially factual sites that detail and evaluate suicide methods (from 9%, 2007 to 21.7%, 2014). Hits for dedicated suicide sites increased (from 19% to 23%), while formal help sites were less visible (from 13% to 6.5%). Overall, 54% of hits contained information about new high-lethality methods. LIMITATIONS: We did not search for help sites so cannot assess the balance of suicide promoting versus preventing sites available online. Social media was beyond the scope of this study. CONCLUSIONS: Working with ISPs and search engines would help optimise support sites. Better site moderation and implementation of suicide reporting guidelines should be encouraged. PMID- 26546773 TI - Emotion dysregulation, psychological inflexibility, and shame as explanatory factors between neuroticism and depression. AB - BACKGROUND: The association between neuroticism and depression is well documented. However, neuroticism is a general risk factor associated with many forms of psychopathology, such as anxiety, eating, and personality disorders. Past research has suggested that other factors may mediate the relationship between neuroticism and symptoms of particular disorders. METHODS: Self-report questionnaires measuring neuroticism, emotion dysregulation, psychological inflexibility, shame, and symptoms of depression were administered to 105 inpatient adolescents (aged 12-17). The current study examined three factors (emotion dysregulation difficulties, psychological inflexibility, and shame) as concurrent mediators of the neuroticism/depression association. RESULTS: Neuroticism was significantly associated with depression, as expected. Neuroticism was also associated with emotion dysregulation and psychological inflexibility, which, in combination, fully mediated the association between neuroticism and depression. Shame was not significantly associated with neuroticism or depression, when controlling for anxiety, externalizing, sex, and age. Follow-up analyses examined six sub-factors of emotion dysregulation as multiple mediators of the neuroticism/depression association. Goal directed behavior, lack of emotion regulation strategies, and impulse control were significant mediators, controlling for the other three emotion dysregulation sub factors. LIMITATIONS: The study is limited by the cross sectional design, sample size, and self-report measurement. CONCLUSIONS: Despite limitations, this study demonstrated that the link between neuroticism and depression is explained by both emotion dysregulation and psychological inflexibility and that specific emotion dysregulation facets may be at play in adolescent depression. PMID- 26546774 TI - Annual direct health care expenditures and employee absenteeism costs in high risk, low-income mothers with major depression. AB - BACKGROUND: To determine the health care and labor productivity costs associated with major depressive disorder in high-risk, low-income mothers. METHODS: This study was conducted using the 1996-2011 Medical Expenditure Panel Survey (MEPS). The MEPS is a nationally-representative database that includes information on health care utilization and expenditures for the civilian, non-institutionalized population in the United States. High-risk mothers were between the ages of 18-35 years, and either unmarried, receiving Medicaid, or with incomes less than 300% of the Federal Poverty Level. Mothers were categorized as being depressed if they had an ICD-9 diagnosis code of 296 or 311 (N=2310) or not depressed (N=18,221). Insurer expenditures, out-of-pocket (OOP) expenses, and lost wage earnings were calculated. RESULTS: After controlling for comorbidities, demographics, region, and year, high-risk depressed mothers were more likely to incur insurer (0.84 vs. 0.79) and OOP expenses (0.84 vs. 0.81) and to have higher insurer ($4448 vs. $3072) and OOP expenses ($794 vs. $523). Depression significantly increased the likelihood of missing work days (OR=1.40; p<0.01). Depression increased overall direct health care expenditures by $1.89 billion (range=$1.28-$2.60 billion) and indirect costs by $523 million annually, with a range of $353-$719 million. CONCLUSIONS: In this high-risk population, the direct and indirect aggregate costs of depression-related to health care expenditures and lost work productivity were substantial. These findings establish a quantifiable cost for policy makers and highlight the need to target this population for prevention and treatment efforts. PMID- 26546775 TI - The identification of symptom-based subtypes of depression: A nationally representative cohort study. AB - BACKGROUND: In recent years, researchers have used various techniques to elucidate the heterogeneity in depressive symptoms. This study seeks to resolve the extent to which variations in depression reflect qualitative differences between symptom categories and/or quantitative differences in severity. METHODS: Data were used from the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face survey of the adult general population. In a subsample of respondents with a lifetime key symptom of depression at baseline and who participated in the first two waves (n=1388), symptom profiles at baseline were based on symptoms reported during their worst lifetime depressive episode. Depressive symptoms and DSM-IV diagnoses were assessed with the Composite International Diagnostic Interview 3.0. Three latent variable techniques (latent class analysis, factor analysis, factor mixture modelling) were used to identify the best subtyping model. RESULTS: A latent class analysis, adjusted for local dependence between weight change and appetite change, described the data best and resulted in four distinct depressive subtypes: severe depression with anxiety (28.0%), moderate depression with anxiety (29.3%), moderate depression without anxiety (23.6%) and mild depression (19.0%). These classes showed corresponding clinical correlates at baseline and corresponding course and outcome indicators at follow-up (i.e., class severity was linked to lifetime mental disorders at baseline, and service use for mental health problems and current disability at follow-up). LIMITATIONS: Although the sample was representative of the population on most parameters, the findings are not generalisable to the most severely affected depressed patients. CONCLUSIONS: Depression could best be described in terms of both qualitative differences between symptom categories and quantitative differences in severity. In particular anxiety was a distinguishing feature within moderate depression. This study stresses the central position anxiety occupies in the concept of depression. PMID- 26546776 TI - Cytokines and their association with insulin resistance in obese pregnant women with different levels of physical activity. AB - BACKGROUND: Cytokines contribute to insulin resistance in pregnancy, but the role of distinct cytokines is not fully understood. OBJECTIVES: To study whether cytokines produced by tissues other than skeletal muscle are associated with glucose and insulin metabolism activity in overweight and obese women and to study whether these associations can be modified by physical activity. METHODS: A longitudinal study with 44 overweight and obese pregnant women was conducted. Changes in cytokines levels (IFN-gamma, IP-10, IL1-alpha, MIP1-alpha, adiponectin and leptin) and ICAM1 from early (15wk) to late (32wk) pregnancy were determined. Physical activity was measured objectively with accelerometers. In linear regression models, the associations between (changes in) cytokine levels and fasting glucose, fasting insulin and HOMA-IR were studied. RESULTS: Both IFN gamma and IP-10 levels increased from early to late pregnancy, and adiponectin levels decreased. IFN-gamma and IP-10 were positively associated with fasting glucose, whereas IL-1alpha, ICAM1 and adiponectin were inversely associated with insulin and insulin resistance. The association of IL-1alpha with insulin and insulin resistance was only found in women with low levels of physical activity. CONCLUSIONS: IFN-gamma, IP-10, IL1-alpha, ICAM1, and adiponectin may play a role in glucose and insulin metabolism in pregnancy. The relationship of IL-1alpha with insulin and insulin resistance might be moderated by levels of physical activity. Further studies are required to confirm the role of these cytokines in glucose and insulin metabolism in obese pregnant women. PMID- 26546777 TI - IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy. AB - The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF alpha/CD4(+) T cell count, TNF-alpha/CD8(+) T cell count and IFN-gamma/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-beta (p<0.05) and IFN-gamma (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-beta and IFN-gamma levels. PMID- 26546778 TI - Cigarette smoke-mediated oxidative stress induces apoptosis via the MAPKs/STAT1 pathway in mouse lung fibroblasts. AB - Cigarette smoking is the major aetiologic factor in chronic obstructive pulmonary disease (COPD). Lung fibroblasts are key participants in the maintenance of the extracellular matrix within the lung parenchyma. However, it still remains unknown how pulmonary fibroblasts are affected by cigarette smoking. Therefore, in this study, we isolated lung fibroblasts from mice and determined the apoptotic mechanism in response to cigarette smoke extract (CSE). When the lung fibroblasts were exposed to CSE, the generation of ROS was increased as shown by H2-DCFDA staining and Flow Cytometry. By immunocytochemistry, Ki67 expressing cells gradually decreased in a dose-dependent manner. The nitrite concentration in the supernatants increased, while the SOD activity and GSH recycling decreased in response to CSE. CSE increased the mRNA levels of TNF-alpha and COX-2, and the secretory proteins TNF-alpha and IL-6 increased as measured by ELISA. We next determined whether this inflammatory process is associated with the Bax/Bcl-2 apoptosis pathway. The Bax/Bcl-2 mRNA ratio increased, and cleaved caspase-3 protein was activated in the lung fibroblasts treated with CSE. Moreover, CSE induced the phosphorylation of STAT1 at Tyr701/Ser727 and increased the activation of ERK1/2, p38, and JNK in the MAPK pathway. Taken together, these data suggest that CSE-mediated inflammation alters the redox regulation via the MAPK-STAT1 pathway, leading to intrinsic apoptosis of lung fibroblasts. PMID- 26546779 TI - Toxic effects of male Perna viridis gonad exposed to BaP, DDT and their mixture: A metabolomic and proteomic study of the underlying mechanism. AB - Benzo(a)pyrene and dichlorodiphenyltrichloroethane are typical persistent organic pollutants, and also the widespread environmental estrogens with known toxicity towards green mussels Perna viridis. In this study, the toxicological effects of BaP and DDT and their mixture were assessed in green mussel gonads using proteomic and metabolomic approaches. Metabolomics by NMR spectroscopy revealed that BaP did not show obvious metabolite changes in the gonad of male green mussel. DDT mainly caused some disturbance of osmotic regulation and energy metabolism by changing BCAAs, alanine, threonine, arginine, etc., unknown metabolite (3.53 ppm), glycine, homarine and ATP at different levels. However, the mixture of BaP and DDT mainly caused some disturbance in osmotic regulation and energy metabolism by differentially altering branched chain amino acids, glutamate, alanine, arginine, unknown metabolite (3.53 ppm), glycine, 4 aminobutyrate, dimethylglycine, homarine and ATP. The results suggest that DDT alone may cause most of metabolites changes in the mixture exposed male mussel gonad, and the results also show that the male P. viridis gonad was more sensitive to DDT than BaP exposures. Proteomic study showed that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced signal transduction, oxidative stress, spermatogenesis, etc. in the male green mussel gonad; whereas DDT exposure altered proteins that were associated with signal transduction, oxidative stress, cytoskeleton and cell structure, cellular organization, energy metabolism, etc. However, the mixture of BaP and DDT affected proteins related to cytoskeleton and cell structure, oxidative stress, cellular organization, etc. This research demonstrated that metabolomic and proteomic approaches could better elucidate the underlying mechanism of environmental pollutants gonad toxicity. PMID- 26546780 TI - A novel cell-based assay for the evaluation of immune- and inflammatory-related gene expression as biomarkers for the risk assessment of drug-induced liver injury. AB - Drug-induced liver injury (DILI) is a major problem in drug development. Although some in vitro methods assessing DILI risk that utilize hepatic cell death or cellular stress as markers have been developed, the predictive ability of these tests is low. In this study, we sought to develop a novel cell-based assay for the risk assessment of DILI that considers drug metabolism as well as immune- and inflammatory-related gene expression. To accomplish this goal, human hepatoma HepaRG or HepG2 cells were treated with 96 drugs with different clinical DILI risks. The conditioned media were subsequently used to treat human promyelocytic leukemia HL-60 cells, and the mRNA expression levels of immune- and inflammatory related genes in the cells were measured. An area under the receiver operating characteristic curve (ROC-AUC) was calculated to evaluate the predictive performance of the mRNA levels as markers to discriminate DILI risk. The expression of interleukin-8 (IL-8) in HL-60 cells treated with conditioned media from HepaRG cells (HL-60/HepaRG) exhibited the highest ROC-AUC value of 0.758, followed by the expression of IL-1beta in HL-60/HepaRG (ROC-AUC: 0.726). Notably, the ROC-AUC values of these genes were higher in HL-60/HepaRG than in HL 60/HepG2, which suggests that HL-60/HepaRG has a higher potential for detecting the metabolic activation of drugs. An integrated score calculated from the levels of S100 calcium-binding protein A9 (S100A9), IL-1beta, and IL-8 more precisely determined the DILI risks than individual gene expression did. The developed cell based assay that utilizes immune-related gene expression would aid in the assessment of potential DILI risks. PMID- 26546781 TI - Characterization and function of the 3-hydroxy-3-methylglutaryl-CoA reductase gene in Alisma orientale (Sam.) Juz. and its relationship with protostane triterpene production. AB - Protostane triterpenes from Alisma orientale (Sam.) Juz. have exhibited distinct pharmacological properties that are currently in high demand. 3-Hydroxy-3 methylglutaryl-CoA reductase (HMGR) is considered the first rate-limiting enzyme in isoprenoid biosynthesis via the mevalonic acid (MVA) pathway. In this study, we cloned a full-length cDNA of A. orientale (Sam.) Juz. HMGR (AoHMGR; 2252 bp; GenBank accession no. KP342318) with an open reading frame (ORF) of 1809 bp. The deduced protein sequence contained four conserved motifs and exhibited homology with HMGR proteins from other plants. We next expressed the cloned gene in Escherichia coli BL21 (Rosetta) cells, collected the expressed products, and incubated those with 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to determine enzymatic activity. GC/MS analysis revealed that the products were able to catalyze HMG-CoA and NADPH to form MVA. The purified protein was used to immunize New Zealand rabbits and prepare an antibody against AoHMGR. Western blot results demonstrated that the antibodies specifically recognized AoHMGR protein in A. orientale (Sam.) Juz. We then established a rapid test to detect AoHMGR protein in the plant, and found the tuber to be the most AoHMGR protein-abundant organ in A. orientale (Sam.) Juz. Furthermore, we detected the expression level of AoHMGR and contents of the main active component, Alisol B 23-acetate, at different growth phases of A. orientale (Sam.) Juz. A significant positive correlation was identified, indicating that AoHMGR represents a key enzyme in the synthetic pathway of protostane triterpenes. PMID- 26546782 TI - Mycorrhiza and PGPB modulate maize biomass, nutrient uptake and metabolic pathways in maize grown in mining-impacted soil. AB - Abiotic stress factors including poor nutrient content and heavy metal contamination in soil, can limit plant growth and productivity. The main goal of our study was to evaluate element uptake, biomass and metabolic responses in maize roots growing in mining-impacted soil with the combination of arbuscular mycorrhiza (My) and plant growth promoting bacteria (PGPB/B). Maize plants subjected to PGPB, My and combined treatments showed a significant increase in biomass and uptake of some elements in shoot and root. Metabolite analysis identified 110 compounds that were affected >=2-fold compared to control, with 69 metabolites upregulated in the My group, 53 metabolites in the My+B group and 47 metabolites in B group. Pathway analysis showed that impact on glyoxylate and dicarboxylate metabolism was common between My and My+B groups, whereas PGPB group showed a unique effect on fatty acid biosynthesis with significant increase in palmitic acid and stearic acid. Differential regulation of some metabolites by mycorrhizal treatment correlated with root biomass while PGPB regulated metabolites correlated with biomass increase in shoot. Overall, the combination of rhizospheric microorganisms used in our study significantly increased maize nutrient uptake and growth relative to control. The changes in metabolic pathways identified during the symbiotic interaction will improve our understanding of mechanisms involved in rhizospheric interactions that are responsible for increased growth and nutrient uptake in crop plants. PMID- 26546784 TI - Stress influences environmental donation behavior in men. AB - Stress has been found to have both positive and negative effects on prosocial behavior, suggesting the involvement of moderating factors such as context and underlying motives. In the present study, we investigated the conditions under which acute stress leads to an increase vs. decrease in environmental donation behavior as an indicator of prosocial behavior. In particular, we examined whether the effects of stress depended on preexisting pro-environmental orientation and stage of the donation decision (whether or not to donate vs. the amount to be donated). Male participants with either high (N=40) or low (N=39) pro-environmental orientation were randomly assigned to a social stress test or a control condition. Salivary cortisol was assessed repeatedly before and after stress induction. At the end of the experiment, all subjects were presented with an opportunity to donate a portion of their monetary compensation to a climate protection foundation. We found that stress significantly increased donation frequency, but only in subjects with low pro-environmental orientation. Congruously, their decision to donate was positively associated with cortisol response to the stress test and the emotion regulation strategy mood repair, as well as accompanied by an increase in subjective calmness. In contrast, among the participants who decided to donate, stress significantly reduced the donated amount of money, regardless of pro-environmental orientation. In conclusion, our findings suggest that acute stress might generally activate more self-serving motivations, such as making oneself feel better and securing one's own material interests. Importantly, however, a strong pro-environmental orientation partially prevented these effects. PMID- 26546785 TI - The predictive value of cortisol levels on 2-year course of depression in older persons. AB - BACKGROUND: Depressive disorders in older persons are associated with an altered functioning of the Hypothalamic-Pituitary-Adrenal (HPA)-axis. In adults, a lower cortisol awakening response is a predictor of a worse prognosis of depression, but to date longitudinal studies in older depressed persons are lacking. We hypothesised that a lower cortisol awakening response is also associated with poorer course of depression in later life. METHODS: Data were derived from the Netherlands Study of Depression in Older Persons (NESDO). Participants with a 6 month Major Depressive Disorder (MDD), who provided 2-year follow-up data, were included (n=246). Logistic regression analyses were conducted to examine the association between diurnal cortisol levels and depressive status at 2-year follow-up. RESULTS: Both lower (OR=3.54; 95% CI=1.59-7.89) and higher evening cortisol levels (OR=2.41; 95% CI=1.09-5.35) at baseline were associated with poorer prognosis of MDD. Low dexamethasone suppression was associated with poorer course (OR=2.37; 95% CI=1.09-5.16), but failed to reach significance after additional adjustment for severity and chronicity of MDD (OR=1.98; 95% CI=0.89 4.42). Cortisol awakening response was not significantly associated with course. Since smoking has a great impact on cortisol levels, we conducted post-hoc analyses including non-smokers only, indicating that lower evening cortisol levels (OR=2.83, 95% CI=1.31-6.13) predicted unfavourable course. CONCLUSIONS: This first longitudinal study on cortisol and prognosis of depression in older persons demonstrates that in particular lower evening cortisol levels may predict poorer course in MDD. This finding may have clinical implications. Evening cortisol values may serve as a marker to identify persons at risk for an unfavourable course. PMID- 26546783 TI - The role of cytokines in the pathophysiology of suicidal behavior. AB - OBJECTIVE: Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. METHODS: We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. RESULTS: The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, IL-4, and soluble Il-2 receptors. CONCLUSIONS: Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk. PMID- 26546786 TI - The influence of Rho-kinase inhibition on acetic acid-induced detrusor overactivity. AB - AIMS: Accumulating evidence has shown that Rho-kinase (ROCK) is involved in the regulation of bladder contraction. Our objective was to examine whether the ROCK inhibitor, GSK 269962, could prevent acetic acid (AA)-induced detrusor overactivity and to assess its influence on urine production (UP) and mean arterial pressure (MAP). METHODS: The bladder was catheterized from the external urethral orifice. 0.25 % (AA) solution was infused into the bladder for 5 min. In the same session a catheter was inserted into the apex of the bladder dome. In order to measure the blood pressure, the carotid artery was cannulated. Three days after the intravesical instillation of AA, the ROCK-GSK 269962 inhibitor was administered in a single dose of 10 mg/kg and a cystometry was carried out, along with a 24 hr measurement of UP and MAP. RESULTS: GSK 269962 reversed the changes induced by AA causing a drop in basal pressure, threshold pressure, micturition voiding pressure, bladder contraction duration, relaxation time, detrusor overactivity index, amplitude, and frequency of nonvoiding contractions while an increase in voided volume, post-void residual, volume threshold, voiding efficiency, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. ROCK inhibition did not show any significant changes in UP and MAP. DISCUSSION: The results obtained indicate that ROCK inhibition may ameliorate AA-induced bladder overactivity. CONCLUSION: ROCK inhibitors appear to represent a potentially attractive pharmacological option for the treatment of lower urinary tract disorders associated with changes in detrusor contractility. Neurourol. Urodynam. 36:263-270, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26546787 TI - Alkali-solubilized organic matter from sludge and its degradability in the anaerobic process. AB - This study investigates alkali-solubilized dissolved organic matter (DOM) and its fate in the anaerobic treatment process. DOM was fractionated into high molecular weight (HMW) protein-like substances (PL), HMW saccharide-like substances (SL), low molecular weight (LMW) PL, LMW SL, and humic acid-like substances (HAL). The results indicate alkali-solubilized DOM is primarily composed of LMW PL, HMW SL, and HAL. Alkaline pretreatment improved the overall anaerobic degradability of DOM in sludge (removal efficiency of total DOM increased by 28.4%). However, certain DOM fractions (mainly HMW PL and HAL) exhibited low degradability during anaerobic treatment, primarily caused by the low degradability of aromatic groups (such as aromatic amine groups from tryptophan-like PL). Alkaline pretreatment also resulted in an increase of residual DOM, which is mainly composed of HAL (52.9%) and HMW SL (49.9%). PMID- 26546788 TI - Long term effect of alkali types on waste activated sludge hydrolytic acidification and microbial community at low temperature. AB - The effect of four alkali reagents (NaOH, KOH, Ca(OH)2, mixed alkali) on waste activated sludge (WAS) hydrolytic acidification and microbial community was studied in semi-continuous fermentation systems at low temperature (15 degrees C) over long term operational time (65day). The results showed that protein and polysaccharide of NaOH (124.26, 11.92) was similar to that of KOH (109.53, 11.30), both were higher than Ca(OH)2 (70.66, 3.74) and mixed alkali (90.66, 8.71). The short chain fatty acids (SCFAs) of NaOH (231.62) was higher than KOH (220.62mg chemical oxygen demand (COD)/g VSS). Although Ca(OH)2 system had strong acidification capacity, the shortage of SCFAs occurred due to the low activity of hydrolase. Illumina MiSeq sequencing revealed that Tissierella and Erysipelothrix were enriched in the NaOH and Ca(OH)2 systems, where Peptostreptococcaceae incertae_sedis was enriched in the NaOH and KOH systems, less Anaerolinea was involved in Ca(OH)2 condition. PMID- 26546789 TI - Experiences with food insecurity and risky sex among low-income people living with HIV/AIDS in a resource-rich setting. AB - BACKGROUND: Forty-nine million individuals are food insecure in the United States, where food insecurity and HIV/AIDS are prevalent among the urban poor. Food insecurity is associated with risky sexual behaviours among people living with HIV/AIDS (PLHIV). No qualitative studies, however, have investigated the mechanisms underlying this relationship either in a resource-rich setting or among populations that include men who have sex with men (MSM). METHODS: Semi structured in-depth interviews were conducted with 34 low-income PLHIV receiving food assistance in the San Francisco Bay Area. The interviews explored experiences with food insecurity and perceived associations with sexual risk behaviours. Interviews were conducted in English, audio-recorded and transcribed verbatim. Transcripts were coded and analyzed according to content analysis methods using an inductive-deductive approach. RESULTS: Food insecurity was reported to be a strong contributor to risky sexual practices among MSM and female participants. Individuals described engaging in transactional sex for food or money to buy food, often during times of destitution. Participants also explained how food insecurity could lead to condomless sex despite knowledge of and desire to use safe sexual practices, largely because the need to obtain food in the short term was prioritized over the desire to use barrier protection. CONCLUSIONS: Our data extend previous research by demonstrating that food insecurity contributes to transactional and unprotected sex among urban poor individuals in a resource-rich setting, including among MSM. These findings underscore the importance of public health and social intervention efforts focused on structural inequalities. PMID- 26546790 TI - Anticipatory and consummatory effects of (hedonic) chocolate intake are associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults. AB - BACKGROUND: Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown. METHODS: To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale. RESULTS: The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non palatable one. CONCLUSIONS: When motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity. PMID- 26546791 TI - Unusual Chlorination Patterns of Three IPR Isomers of C88 Fullerene in C88 (7)Cl12/24 , C88 (17)Cl22 , and C88 (33)Cl12/14. AB - High-temperature chlorination of three IPR isomers of fullerene C88 , C2 -C88 (7), Cs -C88 (17), and C2 -C88 (33), resulted in the isolation and X-ray structural characterization of C88 (7)Cl12 , C88 (7)Cl24 , C88 (17)Cl22 , and C88 (33)Cl12/14 . Chlorination patterns of C88 (7) and C88 (33) isomers are unusual in that one or more pentagons remain free from chlorination while some other pentagons are occupied by two or three Cl atoms. The addition patterns of the isolated chlorides are discussed in terms of the distribution of twelve pentagons on the carbon cages and the formation of stabilizing isolated C=C bonds and benzenoid rings. PMID- 26546792 TI - Memory for action: from cognitive models to clinical evaluation. PMID- 26546793 TI - Social interaction is associated with changes in infants' motor activity. AB - BACKGROUND: In developmental research, infants are commonly assumed to be early stakeholders in interactions with their caregivers. The tools that infants can use to interact with others vary from visual contact to smiling or vocalizing, and also include motor activity. However, surprisingly few studies have explored how the nature and context of social interactions affect infants' engagement in motor activity. METHODS: We investigated the kinematic properties of foot and face movements produced by 11 infants aged between 5 and 9 months during six contrasting dyadic episodes (i.e. passive presence of a stranger or the infant's mother, weak or intense interaction with the stranger/mother as she sings a nursery play song). RESULTS: The infants' face and foot motor activity was significantly reduced during the interactive episodes, compared with the episodes without any interaction, in both the mother and stranger conditions. Furthermore, the level of their motor activity was significantly lower in the stranger condition than in the mother one for some parameters. CONCLUSION: These results are in line with those reported by previous studies and confirm the relevance of using motor activity to delineate the early forms of interactive episodes in infants. PMID- 26546794 TI - [Dignity and Ethics of Care in the Neurodegenerative Diseases]. AB - In the context of neurodegenerative diseases the doctor is called more than in other areas to respond not only to the simple question of health, but also to the need of assistance, which implicates the necessity of relationship, too. The scheme of symptom diagnosis treatment healing is to be replaced in these cases with a treatment based on an open system of uncertain length and results. It is a model called "medicine of incurable", which aims to combat the discomfort of the disease rather than the fight against the disease. In this perspective, the commitment to ensure a quality of life to the sick in itself means attention to his dignity, which is expressed in acting towards him treating him always as a person, that is protagonist of his life, and then to recognize his right to be assisted in physical, psychological and spiritual dimensions. In this model it becomes particularly important to converse with the patient, even if affected by cognitive pathologies, as well as to stimulate hope, with the belief that human being, if properly supported, is still able, even in extremely critical situations, to make out of his personal experience a chance to grow, thanks to the construction of new balances, however weak they may be. PMID- 26546795 TI - [Neuroethics and Human Vulnerability in Philosophical Perspective]. AB - This article tries to assess the potentials and limits of neuroethics. It argues that neuroscience and ethics should collaborate each other with mutual respect and preservation of their respective identities, scientific in the first case and philosophical in the second one ( neuroethics as cooperation). The text develops also a criticism in front of any attempt to replace the philosophical ethics by the neurosciences ( neuroethics as substitution). Consequently, the most appropriate ontological and anthropological foundations are explored to develop a cooperative neuroethics. These foundations refer to the Aristotelian hylomorphic conception of the substances. On such foundations it is possible to develop a collaborative neuroethics which includes two aspects: on the one hand, we have an ethics of neuroscience and, on the other one, a neuroscience of ethics. The first one shows us how to conduct neuroscience while preserving human dignity. The second one teaches us about the neurobiological basis of our moral agency. These bases enable our moral behavior without determining it. By studying them our vulnerability as moral agents emerges as evidence. This vulnerability, which is rooted in the very human nature, must be, as it is argued along the last pages of the text, recognized as well as mitigated. PMID- 26546796 TI - [Neuroethics: Ethical Endowments of Human Brain]. AB - The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the "ethical endowments" of each person, common to all human beings, is "embedded" in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind. PMID- 26546797 TI - [Regulation (EU) No 536/2014 on Clinical Trials and Vulnerable Groups]. AB - A complete review of the normative established for clinical trials in vulnerable patient is performed. To do that, the basis is the last European norm, that is, the Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (Text with EEA relevance). It is checked all related to vulnerable patients from the previous European norm. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 and the corresponding transpositions into Spanish law by Royal Decree 223/2004 , of February 6, 2004 , whereby clinical drug trials and Law 29/2006 of 26 July, on guarantees and regulates use rational use of medicines and health products. PMID- 26546798 TI - [Twenty Five Years of Cuadernos de Bioetica (1990-2015): Present and Future]. AB - In this article a brief history of the journal "Cuadernos de Bioetica" is made, a general analysis of the published works in the diverse journal sections is realized. The last changes in it over recent years are also indicated. The article ends with some considerations on the recent history of the magazine and stating some of the lines of improvement that has raised the current editorial board for the next years. PMID- 26546799 TI - Mapping a Major Gene for Resistance to Rift Valley Fever Virus in Laboratory Rats. AB - The Rift Valley Fever virus (RVFV) presents an epidemic and epizootic threat in sub-Saharan Africa, Egypt, and the Arabian Peninsula, and has furthermore recently gained attention as a potential weapon of bioterrorism due to its ability to infect both livestock and humans. Inbred rat strains show similar characteristic responses to the disease as humans and livestock, making them a suitable model species. Previous studies had indicated differences in susceptibility to RVFV hepatic disease among various rat strains, including a higher susceptibility of Wistar-Furth (WF) compared to a more resistant Lewis (LEW) strain. Further study revealed that this resistance trait exhibits the pattern of a major dominant gene inherited in Mendelian fashion. A genome scan of a congenic WF.LEW strain, created from the susceptible WF and resistant LEW strains and itself resistant to infection with RVFV, revealed 2 potential regions for the location of the gene, 1 on chromosome 3 and the other on chromosome 9. Through backcrossing of WF.LEW rats to WF rats, genotyping offspring using SNPs and microsatellites, and viral challenges of 3 N1 litters, we have mapped the gene to the distal end of chromosome 3. PMID- 26546800 TI - RISKS, REASONS AND RIGHTS: THE EUROPEAN CONVENTION ON HUMAN RIGHTS AND ENGLISH ABORTION LAW. AB - Although there is no right to abort in English law but rather abortion is a crime, the lawful grounds for which are instantiated in the Abortion Act 1967 (as amended by the Human Fertilisation and Embryology Act 1990), the regulation of abortion is sometimes perceived as being fairly 'liberal'. Accordingly, the idea that aspects of English law could be criticised under the European Convention on Human Rights, with which the UK must comply following the Human Rights Act 1998, may seem unlikely. Indeed, English law is compatible with the consensus amongst contracting states that abortion should be available on maternal health grounds. However, analysis of the UK's negative obligations under Article 8 shows that section 1(1)(a) of the Act is problematic as it operates in the first trimester. Further, given the European Court of Human Rights' emphasis on the reduced margin of appreciation once a state has legalised abortion to some degree and its jurisprudence relating to a state's positive obligations, the analysis shows that, while English law may not be problematic in relation to the lack of guidelines relating to the lawful grounds for abortion, it may well be in relation to the lack of a formal system for the review of any two doctors' decision not to grant a termination. Notwithstanding the morally serious nature of the decision to abort, the analysis overall raises questions about the need for at least some degree of abortion law reform, particularly in relation to the first trimester, towards a more autonomy-focused, though time-limited, rights based approach. PMID- 26546802 TI - Ultrasonographic vascular mechanics to assess arterial stiffness: a review. AB - In recent years, the role of arterial stiffness in the development of cardiovascular diseases has been explored more extensively. Local arterial stiffness may be gauged via ultrasound, measuring pulse transit time relative to changing vessel diameters and distending pressures. Recently, direct vessel-wall tracking systems have been devised based on new ultrasonographic methodologies, such as tissue Doppler imaging and speckle-tracking analysis--vascular mechanics. These advances have been evaluated in varying arterial distributions, are proved surrogates of pulse wave velocity, and are ascending in clinical importance. In the course of this review, we describe fundamental concepts and methodologies involved in ultrasound assessment of vascular mechanics. We also present relevant clinical studies and discuss the potential clinical utility of such diagnostic pursuits. PMID- 26546801 TI - Acetyltransferase p300 collaborates with chromodomain helicase DNA-binding protein 4 (CHD4) to facilitate DNA double-strand break repair. AB - Chromatin remodelling is critical for repairing DNA damage and maintaining genomic integrity. Previous studies have reported that histone acetyltransferase p300 and ATP-dependent chromatin remodeler chromodomain helicase DNA-binding protein 4 (CHD4) functions, respectively, in DNA double-strand breaks (DSBs) repair. But the physiological significance of their interaction remains elusive. Here, we showed that p300 and CHD4 were both recruited to the sites of DSBs. Their ablation led to impaired DSBs repair and sensitised cells to laser and the anti-cancer drug, etoposide. Using DR-GFP and EJ5-GFP reporter systems, we found that knockdown of p300 or CHD4 impaired the homologous recombination (HR) repair but no the non-homologous end joining (NHEJ) repair. Furthermore, p300 or CHD4 knockdown respectively suppressed the recruitment of replication protein A (RPA), a key protein for HR, to the DSB sites. In addition, immunofluorescence results showed that knockdown of p300 reduced the recruitment of CHD4 at DSB sites. In turn, CHD4 knockdown also decreased p300 assembly. Moreover, immunoprecipitation and purified protein pull down assay revealed that p300 physically interacted with CHD4 at DNA damage sites, and this interaction was dependent on the chromodomain and ATPase/helicase domain of CHD4 and the CH2, Bd and HAT domains of p300. These results indicate that p300 and CHD4 could function cooperatively at DSB sites and provide a new insight into the detailed crosstalk among the chromatin remodelling proteins. PMID- 26546803 TI - Therapeutic Potential of Human Chorionic Gonadotropin Against Overactive Bladder. AB - Overactive bladder (OAB) is a common form of urinary incontinence, resulting from spontaneous and random contractions of the urinary bladder. The affected individuals have an uncontrollable urge to urinate and experience incontinence and nocturia, which can greatly reduce the quality of daily life. There are several drugs for the treatment, and all of them have serious side effects. The following findings suggested that human chorionic gonadotropin (hCG) has a therapeutic potential that is worth investigating for the treatment of OAB. The finding are (1) human detrusor muscle contains hCG receptors, (2) detrusor muscle becomes quiescent during pregnancy, (3) hCG can inhibit detrusor muscle contractions induced by cholinergic stimulation in rats, and (4) hCG can mimic the anticholinergic drug on detrusor muscle contractions. PMID- 26546804 TI - Re: "Associations of Body Mass Index, Smoking, and Alcohol Consumption With Prostate Cancer Mortality in the Asia Cohort Consortium". PMID- 26546805 TI - Two Authors Reply. PMID- 26546806 TI - Upregulated CDK16 Expression in Serous Epithelial Ovarian Cancer Cells. AB - BACKGROUND: As CDK-16 has been shown to be upregulated in several transformed cancer lines, we hypothesized that the cyclin-dependent kinase 16 (CDK-16) may be upregulated in serous epithelial ovarian cancer (EOC) cells. Therefore, we comparatively examined the mRNA and protein expression of CDK-16 in samples resected from serous EOC patients and normal controls. MATERIAL AND METHODS: Tissue samples were collected from 70 serous EOC patients and 40 normal controls. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess mRNA expression. CDK-16 protein expression was assessed by semi-quantitative immunohistochemical staining. Differences in mRNA and protein expression between serous EOC cells and normal tissue cells were tested with the Kruskal-Wallis test and analysis of variance (ANOVA). RESULTS: Both CDK 16 mRNA and protein expression were significantly higher in serous EOC tumor cells as compared to normal control ovarian cells (p<0.01). Although there was no significant correlation between CDK-16 mRNA expression and serous EOC stage (p=0.0794), there was a significant correlation between CDK-16 mRNA expression and serous EOC grade (p<0.0001). Moreover, there were significant correlations between CDK-16 protein expression and serous EOC stage (p<0.0001) and grade (p<0.0001). CONCLUSIONS: CDK-16 upregulation in serous EOC cells may represent a negative feedback loop to promote ovarian cell differentiation in malignantly transformed serous EOC cells. Further in-depth investigation on CDK-16's role in serous EOC is needed. PMID- 26546807 TI - Literature review in biomedical research: useful search engines beyond PubMed. PMID- 26546808 TI - Addressing contact tracing challenges-critical to halting Ebola virus disease transmission. AB - BACKGROUND: Delayed and ineffective contact tracing contributed to the extensive transmission of Ebola virus disease (EVD) in the 2014-2015 West African outbreak. Understanding and addressing the challenges to implementing and managing contact tracing is essential to stopping EVD transmission and preventing large-scale EVD outbreaks in the future. METHODS: Interviews were conducted with United States Centers for Disease Control and Prevention staff members engaged in contact tracing activities in the affected West African countries of Sierra Leone, Guinea, Liberia, Senegal, Nigeria, and Mali from September through December 2014. Two staff members from each country were interviewed. The five most frequently cited contact tracing challenges were identified. RESULTS: Challenges have been evident in every step of the contact tracing process from implementation to management, including identifying, locating, and enrolling contact-persons, as well as managing personnel and ensuring contact tracing performance. Common themes observed in all of the affected West African countries have included fear, stigma, and community misperceptions regarding EVD. Countries that have overcome these challenges, ensuring immediate and comprehensive contact tracing, have been successful in halting EVD transmission. CONCLUSIONS: Addressing challenges to contact tracing implementation and management in the West African EVD outbreak is essential to stopping ongoing transmission. PMID- 26546809 TI - Oxalate Formation From Glyoxal in Erythrocytes. AB - OBJECTIVE: To determine whether glyoxal can be converted to oxalate in human erythrocytes. Glyoxal synthesis is elevated in diabetes, cardiovascular disease, and other diseases with significant oxidative stress. Erythrocytes are a good model system for such studies as they lack intracellular organelles and have a simplified metabolism. MATERIALS AND METHODS: Erythrocytes were isolated from healthy volunteers and incubated with varying concentrations of glyoxal for different amounts of time. Metabolic inhibitors were used to help characterize metabolic steps. The conversion of glyoxal to glycolate and oxalate in the incubation medium was determined by chromatographic techniques. RESULTS: The bulk of the glyoxal was converted to glycolate, but ~1% was converted to oxalate. Inclusion of the pro-oxidant, menadione, in the medium increased oxalate synthesis, and the inclusion of disulfiram, an inhibitor of aldehyde dehydrogenase activity, decreased oxalate synthesis. CONCLUSION: The glyoxalase system, which utilizes glutathione as a cofactor, converts the majority of the glyoxal taken up by erythrocytes to glycolate, but a small portion is converted to oxalate. A reduction in intracellular glutathione increases oxalate synthesis and a decrease in aldehyde dehydrogenase activity lowers oxalate synthesis and suggests that glyoxylate is an intermediate. Thus, oxidative stress in tissues could potentially increase oxalate synthesis. PMID- 26546810 TI - Re: Guzel et al: Can Bladder Wall Thickness Measurement Be Used for Detecting Bladder Outlet Obstruction? PMID- 26546811 TI - Effect of Tamsulosin in Lower Urinary Tract Symptom Patients With Metabolic Syndrome. AB - OBJECTIVE: To investigate the efficacy of tamsulosin, a selective alpha-1 blocker, in lower urinary tract symptoms (LUTS) patients with metabolic syndrome (MS). PATIENTS AND METHODS: This prospective, multicenter clinical trial included men and women (20-75 years old) with LUTS, with or without MS. Patients were categorized as MS+ or MS-, respectively, and all of them were administered tamsulosin 0.2 mg per oral once daily for 24 weeks. Patients were assessed based on the International Prostate Symptom Score, King's Health Questionnaire (KHQ), Overactive Bladder Questionnaire, uroflowmetry with postvoid residuals, and MS factors (blood pressure, waist-to-hip ratio, and serum levels of fasting blood glucose, triglyceride, and high-density lipoprotein cholesterol) at baseline and at 4, 12, and 24 weeks of treatment. RESULTS: Ninety-two patients were enrolled in this study (53/92 were MS- [57.6%]; 39/92 were MS+ [42.4%]). After 24 weeks of tamsulosin treatment, fasting blood glucose (P = .02) and triglyceride (P < .001) levels of changes were significantly greater in the MS+ group than in the MS- group. Total International Prostate Symptom Score, total Overactive Bladder Questionnaire score, and the scores of each question on the KHQ showed significant improvement after treatment without intergroup differences. In KHQ, although improvements in emotional status, sleep quality, fatigue, and personal distress were greater in the MS+ group (P = .05), the difference between the groups did not reach statistical significance. CONCLUSION: Tamsulosin was effective in both LUTS patients with and without MS. Furthermore, tamsulosin had beneficial effects on some of the factors associated with MS. PMID- 26546812 TI - Predictors of Reporting Success With Increased Fluid Intake Among Kidney Stone Patients. AB - OBJECTIVE: To determine how kidney stone patients' knowledge, behaviors, and preferences toward fluid intake differed from those reporting being successful or unsuccessful at increasing fluid intake for prevention. MATERIALS AND METHODS: Three hundred two kidney stone patients filled out a survey on stone history, fluid intake success, and knowledge, behaviors, and preferences toward fluid intake. Responses were compared between those reporting being very successful at fluid intake and those reporting being not successful or only somewhat successful. Self-reported fluid intake success was correlated in a subset of 41 subjects using 24-hour urine volumes. RESULTS: Self-reported fluid intake success correlated significantly with 24-hour urine volumes. Unsuccessful fluid drinkers were less likely to be aware of their future stone risk and were less likely to be counseled on prevention by a urologist. Successful fluid drinkers reported the fewest barriers per person, were more likely to prefer water for fluid intake, and were more likely to like the "taste" of water. Strategies used for remembering to drink varied significantly with those unsuccessful most often reporting "just tried to remember" and those successful at fluid intake most likely to carry a water bottle. All groups reported similar perceived severity from stones, perceived benefits of drinking fluids, and preference for using urine color to monitor hydration. CONCLUSION: Awareness of future stone risk, preference for water, counseling on stone prevention by a urologist, and specific strategies used for increasing fluid intake varied between patients who were successful or unsuccessful with fluid intake. Addressing these differences may help improve fluid intake success. PMID- 26546813 TI - Clitoral Abnormalities in the Absence of Virilization: Etiology and Treatment Strategies. AB - OBJECTIVE: To report 3 cases of pseudoclitoromegaly and to describe the strategies used for differential diagnosis and treatment. METHODS: Three cases and a literature review were described in this study. RESULTS: Three cases referred for treatment of clitoromegaly were in fact cases of pseudoclitoromegaly caused by a hamartoma, a neurofibroma, and a hemangioma of the clitoral prepuce. Abnormal virilization was excluded and the tumors were successfully treated by surgical resection and genital esthetic reconstruction. CONCLUSION: Clitoral abnormalities not associated with virilization syndromes are rare. Isolated abnormalities may affect the clitoris and the clitoral prepuce (pseudoclitoromegaly) and have multiple causes. The most frequent are inclusion cysts secondary to female circumcision, but a multiplicity of tumors, usually benign, may be found. Treatment is surgical, except for most infantile hemangiomas. Before deciding to offer surgical treatment, one should consider the degree of genital deformity and the risks of sensitivity loss and/or clitoral ischemia. PMID- 26546814 TI - New Technique for the Treatment of Buried Penis in Children. AB - OBJECTIVE: To present our treatment experience of buried penis, which has no consensus therapeutic technique for all cases of buried penis, by using a new technique for the repair of this condition, in which the approach is through the ventral penile root. MATERIALS AND METHODS: We performed a retrospective review of 153 patients (median age: 6.5 years) who underwent repair of a buried penis between March 2005 and March 2013. The technique involves the creation of a wedge shaped cut of the ventral penile skin, followed by fixation of the subcutaneous penile skin at the base of the degloved penis to the Buck fascia at the 2- and 10 o'clock positions. The ventral outer preputial skin is split down the midline, and the dorsal inner preputial skin is cut with oblique incision. RESULTS: All patients were followed for an average of 12 months after repair. Other than 2 cases (1.3%) of trapped penis with a ring of scar tissue, which required subsequent excision, there were no complications and the cosmetic appearance was satisfactory. CONCLUSION: The described ventral penile approach is a simple and effective procedure with good cosmetic outcomes and few complications. PMID- 26546815 TI - Very high-density lipoprotein and vitellin as carriers of novel biliverdins IXalpha with a farnesyl side-chain presumably derived from heme A in Spodoptera littoralis. AB - Bilins in complex with specific proteins play key roles in many forms of life. Biliproteins have also been isolated from insects; however, structural details are rare and possible functions largely unknown. Recently, we identified a high molecular weight biliprotein from a moth, Cerura vinula, as an arylphorin-type hexameric storage protein linked to a novel farnesyl biliverdin IXalpha; its unusual structure suggests formation by cleavage of mitochondrial heme A. In the present study of another moth, Spodoptera littoralis, we isolated two different biliproteins. These proteins were identified as a very high-density lipoprotein (VHDL) and as vitellin, respectively, by mass spectrometric sequencing. Both proteins are associated with three different farnesyl biliverdins IXalpha: the one bilin isolated from C. vinula and two new structurally closely related bilins, supposed to be intermediates of heme A degradation. The different bilin composition of the two biliproteins suggests that the presumed oxidations at the farnesyl side-chain take place mainly during egg development. The egg bilins are supposedly transferred from hemolymph VHDL to vitellin in the female. Both biliproteins show strong induced circular dichroism activity compatible with a predominance of the M-conformation of the bilins. This conformation is opposite to that of the arylphorin-type biliprotein from C. vinula. Electron microscopy of the VHDL-type biliprotein from S. littoralis provided a preliminary view of its structure as a homodimer and confirmed the biochemically determined molecular mass of ~350 kDa. Further, images of S. littoralis hexamerins revealed a 2 * 3 construction identical to that known from the hexamerin from C. vinula. PMID- 26546816 TI - MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages. AB - Angiopoietin-like 4 (Angptl4), a secreted protein, is an important regulator to irreversibly inhibit lipoprotein lipase (LPL) activity. Macrophage LPL contributes to foam cell formation via a so-called"molecular bridge" between lipoproteins and receptors on cell surface. It has been reported that macrophage ANGPTL4 suppresses LPL activity, foam cell formation and inflammatory gene expression to reduce atherosclerosis development. Recently, some studies demonstrated that microRNA-134 is upregulated in atherosclerotic macrophages. Here we demonstrate that miR-134 directly binds to 3'UTR of ANGPTL4 mRNA to suppression the expression of ANGPTL4. To investigate the potential roles of macrophage miR-134, THP-1 macrophages were transfected with miR-134 mimics or inhibitors. Our results showed that LPL activity and protein were dramatically increased. We also found that miR-134 activated LPL-mediated lipid accumulation. Collectively, our findings indicate that miR-134 may regulate lipid accumulation and proinfiammatory cytokine secretion in macrophages by targeting the ANGPTL4 gene. Our results have also suggested a promising and potential therapeutic target for atherosclerosis. PMID- 26546817 TI - Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways. AB - Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. PMID- 26546818 TI - Internal ribosome entry site (IRES) from Encephalomyocarditis virus (EMCV) as a tool for shuttle expression plasmids. AB - In eukaryotes, IRES sequences aid the recruitment of factors needed for translation to occur, enabling protein production independent of 5' capped mRNA. Many patents and commercially available plasmids exploit their properties for polycistronic expression of recombinant proteins. However, these applications have been restricted to eukaryotic organisms, since it was thought that elements of this origin were essential for their activity. Here, using two tricistronic vectors designed for expression in mammalian hosts, we present evidence of EMCV IRES activity in prokaryotes. This finding enables the development of new and more versatile plasmid vectors for the production of recombinant proteins in multiple hosts from a single construct. Additionally, it provides new hints for the elaboration of alternative models describing the molecular mechanism of EMCV IRES mediated translation, in the absence of eukaryotic elements that were considered indispensable for its function. PMID- 26546819 TI - Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes. AB - A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring (14)C-CO2 production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. PMID- 26546820 TI - Islet-specific monoamine oxidase A and B expression depends on MafA transcriptional activity and is compromised in type 2 diabetes. AB - Lack or dysfunction of insulin producing beta cells results in the development of type 1 and type 2 diabetes mellitus, respectively. Insulin secretion is controlled by metabolic stimuli (glucose, fatty acids), but also by monoamine neurotransmitters, like dopamine, serotonin, and norepinephrine. Intracellular monoamine levels are controlled by monoamine oxidases (Mao) A and B. Here we show that MaoA and MaoB are expressed in mouse islet beta cells and that inhibition of Mao activity reduces insulin secretion in response to metabolic stimuli. Moreover, analysis of MaoA and MaoB protein expression in mouse and human type 2 diabetic islets shows a significant reduction of MaoB in type 2 diabetic beta cells suggesting that loss of Mao contributes to beta cell dysfunction. MaoB expression was also reduced in beta cells of MafA-deficient mice, a mouse model for beta cell dysfunction, and biochemical studies showed that MafA directly binds to and activates MaoA and MaoB transcriptional control sequences. Taken together, our results show that MaoA and MaoB expression in pancreatic islets is required for physiological insulin secretion and lost in type 2 diabetic mouse and human beta cells. These findings demonstrate that regulation of monoamine levels by Mao activity in beta cells is pivotal for physiological insulin secretion and that loss of MaoB expression may contribute to the beta cell dysfunction in type 2 diabetes. PMID- 26546821 TI - Kruppel-like factor 4 synergizes with CREB to increase the activity of apolipoprotein E gene promoter in macrophages. AB - Kruppel-like factor 4 (KLF4) is a critical regulator of monocyte differentiation and macrophage polarization, and it also plays an important role in several vascular diseases, including atherosclerosis. Apolipoprotein E (apoE) is an essential anti-atherosclerotic glycoprotein involved in lipid metabolism, expressed by the liver, macrophages and other cell types. We hypothesized that KLF4 is involved in apoE gene regulation in macrophages. Our experiments showed that differentiation of THP-1 monocytes to macrophages using PMA was associated with a robust induction of both KLF4 and apoE genes. KLF4 bound to the apoE promoter, as revealed by chromatin immunoprecipitation and DNA pull-down (DNAP) assays, and transactivated the apoE promoter in a dose-dependent manner. Using a series of apoE promoter deletion mutants we revealed the biological activity of multiple KLF4 binding sites located in the [-500/-100] region of apoE promoter. Moreover, overexpression of cAMP-response-element-binding protein (CREB) further increased KLF4 up-regulatory effect on apoE promoter. Despite the fact that no putative CREB binding sites were predicted in silico, we found that in macrophages CREB bound to apoE proximal promoter in the region -200/+4 and even more strongly on -350/-274 region. In similar DNAP experiments using cell extracts obtained from monocytes (lacking KLF4), a very weak binding of CREB was detected, indicating that interaction of CREB with apoE promoter takes place indirectly. In conclusion our results show: (i) a robust synchronized induction of KLF4 and apoE expression during differentiation of monocytes to macrophages; (ii) KLF4 up-regulates apoE gene in a dose-dependent manner; (iii) biologically active KLF4 binding sites are present on apoE promoter and (iv) the interaction of KLF4 with CREB results in an enhanced up-regulatory effect of KLF4 on apoE promoter. Taken together these data provide novel knowledge on apoE gene regulation mechanism in macrophages, and offer insight into the therapeutic potential of KLF4 in atherosclerosis. PMID- 26546822 TI - K(+)-Responsive off-to-on switching of hammerhead ribozyme through dual G quadruplex formation requiring no heating and cooling treatment. AB - Functional RNAs that switch their activities in response to K(+) may sense the intracellular (100 mM) and extracellular (5 mM) K(+) concentrations and regulate their functions accordingly. Previously, we developed a quadruplex hammerhead ribozyme (QHR) whose conformational change, from a duplex to a G-quadruplex, triggered by K(+) results in expression of the activity. However, this QHR required heating and cooling treatment (annealing) to induce the K(+)-responsive conformational change and activity. Here, we developed a new quadruplex hammerhead ribozyme (QHR) system that does not require annealing to induce the K(+)-responsive conformational change and activity. This system is composed of QHR and a G-quadruplex-forming complementary DNA strand (QCS). In the absence of K(+), QCS formed a duplex with QHR, which suppressed the residual activity. Upon elevation of the K(+) concentration, QCS dissociated from QHR was trapped in a G quadruplex, and then QHR could form a G-quadruplex and exerted the activity. The 11.6-fold higher activity was induced by K(+) with an EC50 value of 23 mM, but not by Na(+), which is desirable when the activity switching between the intra /extracellular environment is aimed at. This is the first report of the activation of functional RNA through a 'dual G-quadruplex formation system'. PMID- 26546823 TI - Yeast Cyc8p and Tup1p proteins function as coactivators for transcription of Stp1/2p-dependent amino acid transporter genes. AB - The yeast Cyc8p-Tup1p complex is known to serve primarily as a transcriptional corepressor in a variety of biological processes. However, less is known about its function as a coactivator. Herein, we found tryptophan transporter genes, TAT1 and TAT2, that, when overexpressed, suppressed the slow growth of Deltacyc8. We observed that the addition of tryptophan to Deltacyc8 cultures partially restored cell growth, and the deletion of CYC8 and TUP1 reduced transcriptional levels of TAT1 and TAT2. Tup1p bound to the promoter region of TAT1 and TAT2 genes that were dependent on STP1 and STP2 (encoding DNA-binding activator proteins) for expression. Similarly, transcription of the other Stp1/2p-dependent amino acid transporter (AAT) genes also required CYC8 and TUP1 gene functions. These data indicate that Cyc8p-Tup1p plays a role as a transcriptional coactivator for AAT genes via Stp1/2p activators and that lowering intracellular tryptophan by CYC8 deletion causes slow growth. PMID- 26546824 TI - Characterization of rabbit limbal epithelial side population cells using RNA sequencing and single-cell qRT-PCR. AB - Corneal epithelial stem cells reside in the limbus, a transitional zone between the cornea and conjunctiva, and are essential for maintaining homeostasis in the corneal epithelium. Although our previous studies demonstrated that rabbit limbal epithelial side population (SP) cells exhibit stem cell-like phenotypes with Hoechst 33342 staining, the different characteristics and/or populations of these cells remain unclear. Therefore, in this study, we determined the gene expression profiles of limbal epithelial SP cells by RNA sequencing using not only present public databases but also contigs that were created by de novo transcriptome assembly as references for mapping. Our transcriptome data indicated that limbal epithelial SP cells exhibited a stem cell-like phenotype compared with non-SP cells. Importantly, gene ontology analysis following RNA sequencing demonstrated that limbal epithelial SP cells exhibited significantly enhanced expression of mesenchymal/endothelial cell markers rather than epithelial cell markers. Furthermore, single-cell quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) demonstrated that the limbal epithelial SP population consisted of at least two immature cell populations with endothelial- or mesenchymal-like phenotypes. Therefore, our present results may propose the presence of a novel population of corneal epithelial stem cells distinct from conventional epithelial stem cells. PMID- 26546825 TI - Inhibition of osteoclast differentiation by overexpression of NDRG2 in monocytes. AB - N-Myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family of differentiation-related genes, has been characterized as a regulator of dendritic cell differentiation from monocytes, CD34(+) progenitor cells, and myelomonocytic leukemic cells. In this study, we show that NDRG2 overexpression inhibits the differentiation of U937 cells into osteoclasts in response to stimulation with a combination of macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-kappaB ligand (RANKL). U937 cells stably expressing NDRG2 are unable to differentiate into multinucleated osteoclast-like cells and display reduced tartrate-resistant acid phosphatase (TRAP) activity and resorption pit formation. Furthermore, NDRG2 expression significantly suppresses the expression of genes that are crucial for the proliferation, survival, differentiation, and function of osteoclasts, including c-Fos, Atp6v0d2, RANK, and OSCAR. The activation of ERK1/2 and p38 is also inhibited by NDRG2 expression during osteoclastogenesis, and the inhibition of osteoclastogenesis by NDRG2 correlates with the down-regulation of the expression of the transcription factor PU.1. Taken together, our results suggest that the expression of NDRG2 potentially inhibits osteoclast differentiation and plays a role in modulating the signal transduction pathway responsible for osteoclastogenesis. PMID- 26546826 TI - An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients. AB - Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O2-* and H2O2 being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (1H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine. PMID- 26546828 TI - The Tara Oceans Project: New Opportunities and Greater Challenges Ahead. PMID- 26546827 TI - The relative role of patient physiology and device optimisation in cardiac resynchronisation therapy: A computational modelling study. AB - Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure, however the effective selection of patients and optimisation of therapy remain controversial. While extensive research is ongoing, it remains unclear whether improvements in patient selection or therapy planning offers a greater opportunity for the improvement of clinical outcomes. This computational study investigates the impact of both physiological conditions that guide patient selection and the optimisation of pacing lead placement on CRT outcomes. A multi scale biophysical model of cardiac electromechanics was developed and personalised to patient data in three patients. These models were separated into components representing cardiac anatomy, pacing lead location, myocardial conductivity and stiffness, afterload, active contraction and conduction block for each individual, and recombined to generate a cohort of 648 virtual patients. The effect of these components on the change in total activation time of the ventricles (DeltaTAT) and acute haemodynamic response (AHR) was analysed. The pacing site location was found to have the largest effect on DeltaTAT and AHR. Secondary effects on DeltaTAT and AHR were found for functional conduction block and cardiac anatomy. The simulation results highlight a need for a greater emphasis on therapy optimisation in order to achieve the best outcomes for patients. PMID- 26546829 TI - Update on the molecular biology of dyslipidemias. AB - Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established by genome wide association studies. Secondary factors, obesity, metabolic syndrome, diabetes, renal disease, estrogen and antipsychotics can increase the likelihood of clinical presentation of an individual with predisposed genetic susceptibility to hyperlipoproteinemia. The genetic profiles studied are far from complete and there is room for further characterization of genes influencing lipid levels. Genetic assessment can help identify patients at risk for developing dyslipidemias and for treatment decisions based on 'risk allele' profiles. This review will present the current information on the genetics and pathophysiology of disorders that cause dyslipidemias. PMID- 26546830 TI - Pathological gamma oscillations, impaired dopamine release, synapse loss and reduced dynamic range of unitary glutamatergic synaptic transmission in the striatum of hypokinetic Q175 Huntington mice. AB - Huntington's disease (HD) is a severe genetically inherited neurodegenerative disorder. Patients present with three principal phenotypes of motor symptoms: choreatic, hypokinetic-rigid and mixed. The Q175 mouse model of disease offers an opportunity to investigate the cellular basis of the hypokinetic-rigid form of HD. At the age of 1 year homozygote Q175 mice exhibited the following signs of hypokinesia: Reduced frequency of spontaneous movements on a precision balance at daytime (-55%), increased total time spent without movement in an open field (+42%), failures in the execution of unconditioned avoidance reactions (+32%), reduced ability for conditioned avoidance (-96%) and increased reaction times (+65%) in a shuttle box. Local field potential recordings revealed low-frequency gamma oscillations in the striatum as a characteristic feature of HD mice at rest. There was no significant loss of DARPP-32 immunolabeled striatal projection neurons (SPNs) although the level of DARPP-32 immunoreactivity was lower in HD. As a potential cause of hypokinesia, HD mice revealed a strong reduction in striatal KCl-induced dopamine release, accompanied by a decrease in the number of tyrosine hydroxylase-(TH)- and VMAT2-positive synaptic varicosities. The presynaptic TH fluorescence level was also reduced. Patch-clamp experiments were performed in slices from 1-year-old mice to record unitary EPSCs (uEPSCs) of presumed cortical origin in the absence of G-protein-mediated modulation. In HD mice, the maximal amplitudes of uEPSCs amounted to 69% of the WT level which matches the loss of VGluT1+/SYP+ synaptic terminals in immunostained sections. These results identify impairment of cortico-striatal synaptic transmission and dopamine release as a potential basis of hypokinesia in HD. PMID- 26546832 TI - FoxO3alpha-mediated autophagy contributes to apoptosis in cardiac microvascular endothelial cells under hypoxia. AB - Hypoxic injury of cardiac microvascular endothelial cells (CMECs) is an important pathophysiological event in myocardial infarction, whereas, the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for normal cardiac function and also has been implicated in various cardiovascular diseases. Here we investigated the potential role of autophagy in CMEC dysfunction under hypoxia. CMECs were isolated from SD rats. Hypoxia (6-24h, 1% O2) induced autophagy in CMECs as evidenced by formation of punctate LC3, increased conversion of LC3-I to LC3-II and increased p62 degradation. Importantly, hypoxia-induced apoptosis in CMECs was attenuated by 3 Methyladenine (5mM), an autophagy inhibitor, and aggravated by rapamycin (1.0 MUg/L), an autophagy inducer. Meanwhile, hypoxia increased the nuclear localization of FoxO3alpha, accompanying with the decreased phosphorylation of FoxO3alpha and Akt. FoxO3alpha silencing decreased hypoxia-induced autophagy and the resultant apoptosis. Furthermore, treatment with 3-Methyladenine (10mg/kg/day) improved the endothelial-dependent diastolic function of coronary artery in rats with myocardial infarction. These results indicated that hypoxia induced autophagy formation in CMECs is mediated by FoxO3alpha and contributes to hypoxic injury of hearts. PMID- 26546831 TI - Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. AB - Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (p<0.01) and BA32 (p<0.05) regions and MDD patients with a greater number of depressive episodes displayed thinner cortex in BA32 (p<0.05). Consistent with our previous findings in an overlapping sample, the KynA/3HK ratio and the log KynA/QA were reduced in the MDD group relative to the HC group (p's<0.05) and symptoms of anhedonia were negatively correlated with log KynA/QA in the MDD group (p<0.05). Both KynA/3HK and log KynA/QA at least partially mediated the relationship between diagnosis and cortical thickness of right BA32 (p's<0.05). CRP was inversely associated with BA32 thickness (p<0.01) and KynA/3HK partially mediated the relationship between CRP and the thickness of right BA32 (p<0.05). The results raise the possibility that the relative imbalance between KynA and neurotoxic kynurenine metabolites may partially explain the reductions in mPFC thickness observed in MDD, and further that these changes are more strongly linked to the putative effects of neuroactive kynurenine metabolites than those of inflammatory mediators. PMID- 26546834 TI - De novo assembly and characterization of foot transcriptome and microsatellite marker development for Paphia textile. AB - Paphia textile is an important, aquaculture bivalve clam species distributed mainly in China, Philippines, and Malaysia. Recent studies of P. textile have focused mainly on artificial breeding and nutrition analysis, and the transcriptome and genome of P. textile have rarely been reported. In this work, the transcriptome of P. textile foot tissue was sequenced on an Illumina HiSeqTM 2000 platform. A total of 20,219,795 reads were generated, resulting in 4.08 Gb of raw data. The raw reads were cleaned and assembled into 54,852 unigenes with an N50 length of 829 bp. Of these unigenes, 38.92% were successfully annotated based on their matches to sequences in seven public databases. Among the annotated unigenes, 14,571 were assigned Gene Ontology terms, 5448 were classified to Clusters of Orthologous Groups categories, and 6738 were mapped to 228 pathways in the Kyoto Encyclopedia of Genes and Genomes database. For functional marker development, 5605 candidate simple sequence repeats were identified in the transcriptome and 80 primer pairs were selected randomly and amplified in a wild population of P. textile. A total of 36 loci that exhibited obvious repeat length polymorphisms were detected. The transcriptomic data and microsatellite markers will provide valuable resources for future functional gene analyses, genetic map construction, and quantitative trait loci mapping in P. textile. PMID- 26546833 TI - Dysfunction in amygdala-prefrontal plasticity and extinction-resistant avoidance: A model for anxiety disorder vulnerability. AB - Individuals exhibiting an anxiety disorder are believed to possess an innate vulnerability that makes them susceptible to the disorder. Anxiety disorders are also associated with abnormalities in the interconnected brain regions of the amygdala and prefrontal cortex (PFC). However, the link between anxiety vulnerability and amygdala-PFC dysfunction is currently unclear. Accordingly, the present study sought to determine if innate dysfunction within the amygdala to PFC projection underlies the susceptibility to develop anxiety-like behavior, using an anxiety vulnerable rodent model. The inbred Wistar Kyoto (WKY) rat was used to model vulnerability, as this strain naturally expresses extinction resistant avoidance; a behavior that models the symptom of avoidance present in anxiety disorders. Synaptic plasticity was assessed within the projection from the basolateral nucleus of the amygdala (BLA) to the prelimbic cortical subdivision of the PFC in WKY and Sprague Dawley (SD) rats. While WKY rats exhibited normal paired-pulse plasticity, they did not maintain long-term potentiation (LTP) as SD rats. Thus, impaired plasticity within the BLA-PL cortex projection may contribute to extinction resistant avoidance of WKY, as lesions of the PL cortex in SD rats impaired extinction of avoidance similar to WKY rats. Treatment with d-cycloserine to reverse the impaired LTP in WKY rats was unsuccessful. The lack of LTP in WKY rats was associated with a significant reduction of NMDA receptors containing NR2A subunits in the PL cortex. Thus, dysfunction in amygdala-PFC plasticity is innate in anxiety vulnerable rats and may promote extinction-resistant avoidance by disrupting communication between the amygdala and prefrontal cortex. PMID- 26546835 TI - Genetic regulation analysis reveals involvement of tumor necrosis factor and alpha-induced protein 3 in stress response in mice. AB - In order to study whether Tnfaip3 is related to stress response and further to find it's genetic regulation, we use C57BL/6J (B6) and DBA/2 (D2) mice to built the model of chronic unpredictable mild stress. RT-PCR, Western blotting and immunohistochemistry were used for studying the expression variation of Tnfaip3 in hippocampus tissue of B6 and D2 mice after being stressed. We found that the expression of Tnfaip3 was more remarkably increased in chronic unpredictable stress models than that in untreated mice (P<0.05). It is indicated that Tnfaip3 might take part in the process of stress response. The expression of Tnfaip3 is regulated by a cis-acting quantitative trait locus (cis-eQTL). We identified 5 genes are controlled by Tnfaip3 and the expression of 64 genes highly associated with Tnfaip3, 9 of those have formerly been participate in stress related pathways. In order to estimate the relationship between Tnfaip3 and its downstream genes or network members, we transfected SH-SY5Y cells with Tnfaip3 siRNA leading to down-regulation of Tnfaip3 mRNA. We confirmed a significant influence of Tnfaip3 depletion on the expression of Tsc22d3, Pex7, Rap2a, Slc2a3, and Gap43. These validated downstream genes and members of Tnfaip3 gene network provide us new insight into the biological mechanisms of Tnfaip3 in chronic unpredictable stress. PMID- 26546836 TI - The association of HPV genotype with the regression, persistence or progression of low-grade squamous intraepithelial lesions. AB - BACKGROUND: Human papillomavirus (HPV) is a highly prevalent sexually transmitted virus causing cytological alterations that precede cervical cancer. Approximately 130 genotypes have been sequenced. Low-grade squamous intraepithelial lesions (LSIL) are the most frequent cytological alteration and have an uncertain behavior. OBJECTIVES: To analyze the frequency of HPV types in LSIL and their association with the regression, persistence or progression of these lesions. METHODS: A cohort study of forty patients with LSIL cytology was conducted from December 2007 to March 2011. The follow-up lasted two years and included cytology and colposcopy. HPV detection was performed using PCR, and genotyping was performed using PCR-specific and RFLP techniques. RESULTS: DNA-HPV was detected in 87% (35/40) of the cases, with oncogenic HPV accounting for 76%; type 16 in 32% (11/35) and type 18 in 20%. LSIL regression, persistence and progression rates at the end of the study were 60%, 23% and 17%, respectively. There was 50% regression in lesions in the high oncogenic risk group (types 16 and 18). CONCLUSION: HPV 16 was the most frequent genotype found in LSIL. The persistence and progression of the LSIL were related to the persistence of oncogenic HPV. The longer the follow-up time, the lower the LSIL persistence rate and the higher its regression rate; the progression rate remained stable. In addition to the presence of oncogenic HPV, other factors are necessary for the progression of LSIL. PMID- 26546837 TI - Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases. AB - Small cell lung carcinoma (SCLC) is the most aggressive entity of lung cancer. Rapid cancer progression and early formation of systemic metastases drive the deadly outcome of SCLC. Recent advances in identifying oncogenes by cancer whole genome sequencing improved the understanding of SCLC carcinogenesis. However, tumor material is often limited in the clinic. Thus, it is a compulsive issue to improve SCLC diagnostics by combining established immunohistochemistry and next generation sequencing. We implemented amplicon-based next generation deep sequencing in our routine diagnostics pipeline to analyze RB1, TP53, EP300 and CREBBP, frequently mutated in SCLC. Thereby, our pipeline combined routine SCLC histology and identification of somatic mutations. We comprehensively analyzed fifty randomly collected SCLC metastases isolated from trachea and lymph nodes in comparison to specimens derived from primary SCLC. SCLC lymph node metastases showed enhanced proliferation and frequently a collapsed keratin cytoskeleton compared to SCLC metastases isolated from trachea. We identified characteristic synchronous mutations in RB1 and TP53 and non-synchronous CREBBP and EP300 mutations. Our data showed the benefit of implementing deep sequencing into routine diagnostics. We here identify oncogenic drivers and simultaneously gain further insights into SCLC tumor biology. PMID- 26546838 TI - In vivo imaging of protease activity by Probody therapeutic activation. AB - ProbodyTM therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment. PMID- 26546839 TI - TET peptidases: A family of tetrahedral complexes conserved in prokaryotes. AB - The TET peptidases are large polypeptide destruction machines present among prokaryotes. They form 12-subunits hollow tetrahedral particles, and belong to the family of M42 metallo-peptidases. Structural characterization of various archaeal and bacterial complexes has revealed a unique mechanism of internal compartmentalization and peptide trafficking that distinguishes them from the other oligomeric peptidases. Different versions of the TET complex often co-exist in the cytosol of microorganisms. In depth enzymatic studies have revealed that they are non-processive cobalt-activated aminopeptidases and display contrasting substrate specificities based on the properties of the catalytic chambers. Recent studies have shed light on the assembly mechanism of homo and hetero-dodecameric TET complexes and shown that the activity of TET aminopeptidase towards polypeptides is coupled with its assembly process. These findings suggested a functional regulation based on oligomerization control in vivo. This review describes a current knowledge on M42 TET peptidases biochemistry and discuss their possible physiological roles. This article is a part of the Special Issue entitled: "A potpourri of proteases and inhibitors: from molecular toolboxes to signalling scissors". PMID- 26546840 TI - Natural cysteine protease inhibitors in protozoa: Fifteen years of the chagasin family. AB - Chagasin-type inhibitors comprise natural inhibitors of papain-like cysteine proteases that are distributed among Protist, Bacteria and Archaea. Chagasin was identified in the pathogenic protozoa Trypanosoma cruzi as an approximately 11 kDa protein that is a tight-binding and highly thermostable inhibitor of papain, cysteine cathepsins and endogenous parasite cysteine proteases. It displays an Imunoglobulin-like fold with three exposed loops to one side of the molecule, where amino acid residues present in conserved motifs at the tips of each loop contact target proteases. Differently from cystatins, the loop 2 of chagasin enters the active-site cleft, making direct contact with the catalytic residues, while loops 4 and 6 embrace the enzyme from the sides. Orthologues of chagasin are named Inhibitors of Cysteine Peptidases (ICP), and share conserved overall tri-dimensional structure and mode of binding to proteases. ICPs are tentatively distributed in three families: in family I42 are grouped chagasin-type inhibitors that share conserved residues at the exposed loops; family I71 contains Plasmodium ICPs, which are large proteins having a chagasin-like domain at the C terminus, with lower similarity to chagasin in the conserved motif at loop 2; family I81 contains Toxoplasma ICP. Recombinant ICPs tested so far can inactivate protozoa cathepsin-like proteases and their mammalian counterparts. Studies on their biological roles were carried out in a few species, mainly using transgenic protozoa, and the conclusions vary. However, in all cases, alterations in the levels of expression of chagasin/ICPs led to substantial changes in one or more steps of parasite biology, with higher incidence in influencing their interaction with the hosts. We will cover most of the findings on chagasin/ICP structural and functional properties and overview the current knowledge on their roles in protozoa. PMID- 26546841 TI - Structural biology and genome evolution: An introduction. PMID- 26546842 TI - The Effect of Regeneration Techniques on Periapical Surgery With Different Protocols for Different Lesion Types: A Meta-Analysis. AB - PURPOSE: To evaluate the effect of regeneration techniques (RTs) on the outcome of periapical surgery with different protocols for different lesion types. MATERIALS AND METHODS: PubMed, the Cochrane Library, and Embase were searched from the beginning of time until December 30, 2014. Studies that met the inclusion criteria were systematically evaluated, and a meta-analysis was performed. RESULTS: Eight randomized controlled trials met the inclusion criteria. A significantly better outcome was found in the combination group (membranes plus bone replacement analogues) (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.22 to 0.77; P = .005) and bone replacement analogue only group (RR, 0.48; 95% CI, 0.23 to 0.98; P = .04), whereas no significant beneficial effect was found in the membrane-only group (RR, 0.59; 95% CI, 0.29 to 1.17; P = .13). The use of RTs favorably affected the outcome of periapical through-and-through lesions (RR, 0.38; 95% CI, 0.18 to 0.84; P = .02) and large lesions (>=10 mm) (RR, 0.52; 95% CI, 0.28 to 0.97; P = .04), whereas there was no significant benefit of using RTs for 4-wall lesions (RR, 0.54; 95% CI, 0.27 to 1.07; P = .08). CONCLUSIONS: Both the isolated use of bone replacement analogues and the combination of membranes and bone replacement analogues can improve the outcome of periapical surgery, whereas using membranes alone does not have significantly favorable effects. The use of RTs for through-and-through and large lesions should be recommended. PMID- 26546843 TI - Is Le Fort I Osteotomy Associated With Maxillary Sinusitis? AB - PURPOSE: The purpose of the present study was to investigate the association between Le Fort I osteotomy and the anatomic, radiologic, and symptomatic modifications of the maxillary sinus. MATERIALS AND METHODS: Subjects who had undergone Le Fort I osteotomy from January 2008 to December 2013 were enrolled in a retrospective cohort study. The eligibility criteria were the availability of a cone beam computed tomography (CBCT) scan taken before and 12 to 24 months after the procedure. The exclusion criteria were the unavailability of CBCT scans, the use of tobacco, and previous orthognathic procedures. The primary predictor variable was time (pre-vs postoperative). The primary outcome variables were the sinus volume, mucosal thickening, iatrogenic alterations in the sinus anatomy, and rhinosinusitis symptoms, evaluated using the Sino-Nasal Outcome 20-item Test (SNOT-20). Descriptive statistics were computed for each variable, and paired analyses were used to compare the pre- and postoperative values. RESULTS: The data from 64 subjects (mean age 27; 59.4% were female; median follow-up 32.4 months, range 13 to 66 months) were studied. Postoperatively, 1.6% of the sample (0% preoperatively) had moderate-to-severe and 15.6% (3.1% preoperatively) had mild-to-moderate sinusitis symptoms. The rest of the sample presented with mild to no symptoms. The increase in the SNOT scores after surgery was statistically significant (P = .016). Radiologic evidence of postoperative inflammatory processes affecting the paranasal sinuses was found in 27.3% of the sinuses (9.4% preoperatively). The postoperative Lund-Mackay scores were significantly greater (P = .0005). A 19% decrease was found in the mean postoperative sinus volume, with a 37% incidence of iatrogenic injury. CONCLUSIONS: The study results indicate that Le Fort I osteotomies can have an important impact on sinus health. The postoperative radiologic evidence of maxillary sinus inflammatory processes and the incidence of rhinosinusitis symptoms and iatrogenic damage in these patients have led us to conclude that CBCT scans and the SNOT-20 questionnaire should be used routinely during postoperative monitoring. Larger long-term studies are warranted to clarify the postoperative outcomes and complications. PMID- 26546844 TI - Tight Placement of Erich Arch Bar While Avoiding Wire Fatigue Failure. AB - PURPOSE: To determine the number of wire twists needed to acquire ideal Erich arch bar tightness before wire fatigue failure (fracture) in relation to different distances and angles at which different gauge wires are grasped to provide information to improve the efficiency of arch bar application. MATERIALS AND METHODS: This study mimicked surgical placement of arch bars with 24- and 26 gauge wires. The number of twists to tightness and failure was evaluated when the wire distance between the arch bar and wire holder tip changed (5 vs 10 mm) and when the degree at which the wire was held relative to the tooth axis was changed (45 degrees vs 90 degrees ). A wire shearing test also was used to investigate the fatigability of wires tightened under these same conditions. Wires twisted to tightness, past tightness, and after shearing test movements were visualized with electron microscopy. RESULTS: For 24-gauge wire held at 5 mm, 2.6 to 2.8 twists were needed for wire tightness, with failure after 1.7 to 1.9 twists past tightness; for 24-gauge wire held at 10 mm, 4.4 to 4.9 twists produced tightness, with failure after 2.3 to 2.9 twists past tightness. For 26-gauge wire held at 5 mm, 3.3 to 3.5 twists provided tightness, with 1.6 to 1.8 twists past tightness causing failure; for 26-gauge wire held at 10 mm, 5.1 to 5.5 twists produced tightness, with 3.1 to 3.7 twists past tightness causing failure. At a 45 degrees angle, the wire tightened with fewer twists and showed more resistance to failure with twists past tightness compared with 90 degrees using 24- and 26 gauge wires. In contrast, 24-gauge wire held at a 5-mm distance showed the opposite result, with decreased resistance to failure at the 45 degrees angle. However, the differences were not statistically meaningful. Scanning election microscopy showed no wire fatigue for either angle for 26-gauge wire held at a 5 mm distance and twisted to tightness. After overtightening and oscillation, the 90 degrees angle trials showed fatigue, whereas the 45 degrees angle trials did not. CONCLUSIONS: Holding a 24-gauge wire at 45 degrees to the tooth axis is recommended owing to fewer twists to tightness and more resistance to failure. A 5-mm grasping distance is recommended for experienced surgeons owing to fewer twists to tightness, whereas a 10-mm grasping distance is recommended for novice surgeons owing to a greater tolerance for over-twisting before failure. PMID- 26546845 TI - Complications of Moderate Sedation Versus Deep Sedation/General Anesthesia for Adolescent Patients Undergoing Third Molar Extraction. AB - PURPOSE: To examine the complications resulting from moderate sedation versus deep sedation/general anesthesia for adolescent patients undergoing third molar extraction and determine whether any differences in complication risks exist between the 2 levels of sedation. MATERIALS AND METHODS: We performed a prospective study of the Oral and Maxillofacial Surgery Outcomes System from January 2001 to December 2010. The primary predictor variable was the level of sedation, divided into 2 groups: moderate sedation versus deep sedation/general anesthesia. The primary outcome was the incidence of adverse complications resulting from the sedation level. Differences in the cohort characteristics were analyzed using the independent samples t test, chi(2) test, and analysis of variance, as appropriate. Multivariable logistic regression was used to measure the effect the level of sedation had on the adverse complication rate. RESULTS: Patients in the moderate sedation group had a complication rate of 0.5%, and patients in the deep sedation/general anesthesia group had a complication rate of 0.9%. Compared with moderate sedation, deep sedation/general anesthesia did not pose a significantly increased risk of adverse anesthesia complications (adjusted odds ratio 1.63, 95% confidence interval 0.95 to 2.81; P = .077). CONCLUSIONS: The results of our study have shown that the risk of adverse anesthesia complications is not increased when choosing between moderate and deep sedation/general anesthesia for adolescent patients undergoing third molar extraction. PMID- 26546846 TI - What Is the Cost of Meaningful Use? PMID- 26546847 TI - Second-stage labor: how long is too long? AB - The management of labor has come under increased scrutiny due to the rapid escalation of cesarean delivery in the United States. A workshop of the Society for Maternal-Fetal Medicine, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the American Congress of Obstetricians and Gynecologists was convened to address the rising cesarean delivery rates and one of their recommendations was that the accepted upper limit of the second stage of labor should be increased to >=4 hours in nulliparous women with epidural analgesia and to >=3 hours in parous women with epidural. This led to the inaugural Obstetric Care Consensus series document, "Safe Prevention of the Primary Cesarean Delivery," wherein the workshop recommendations on second-stage labor were promulgated nationally. The result is that the now acceptable maximum length of the second stage of labor exceeds the obstetric precepts that have been in use for >50 years. In this Clinical Opinion, we review the evidence on infant safety, vis-a-vis length of the second stage of labor. Our examination of the evidence begins at the outset of the 20th century and culminates in the very recent (2014) recommendation to abandon the long accepted obstetric paradigm that second-stage labor >3 hours in nulliparous women with labor epidural is unsafe for the unborn infant. We conclude that the currently available evidence fails to support the Obstetric Care Consensus position that longer second-stage labor is safe for the unborn infant. Indeed, the evidence suggests quite the opposite. We suggest that when infant safety is at stake the evidence should be robust before a new clinical road is taken. The evidence is not robust. PMID- 26546848 TI - Accuracy of information about the intrauterine device on the Internet. AB - BACKGROUND: Intrauterine devices (IUDs) are highly effective methods of contraception, but use continues to lag behind less effective methods such as oral contraceptive pills and condoms. Women who are aware of the actual effectiveness of various contraceptive methods are more likely to choose the IUD. Conversely, women who are misinformed about the safety of IUDs may be less likely to use this method. Individuals increasingly use the Internet for health information. Information about IUDs obtained through the Internet may influence attitudes about IUD use among patients. OBJECTIVE: Our objective was to evaluate the quality of information about IUDs among World Wide Web sites providing contraceptive information to the public. STUDY DESIGN: We developed a 56-item structured questionnaire to evaluate the quality of information about IUDs available through the Internet. We then conducted an online search to identify web sites containing information about contraception and IUDs using common search engines. The search was performed in August 2013 and web sites were reviewed again in October 2015 to ensure there were no substantial changes. RESULTS: Our search identified >2000 web sites, of which 108 were eligible for review; 105 (97.2%) of these sites contained information about IUDs. Of sites, 86% provided at least 1 mechanism of the IUD. Most web sites accurately reported advantages of the IUD including that it is long acting (91%), highly effective (82%), and reversible (68%). However, only 30% of sites explicitly indicated that IUDs are safe. Fifty percent (n = 53) of sites contained inaccurate information about the IUD such as an increased risk of pelvic inflammatory disease beyond the insertion month (27%) or that women in nonmonogamous relationships (30%) and nulliparous women (20%) are not appropriate candidates. Among sites, 44% stated that a mechanism of IUDs is prevention of implantation of a fertilized egg. Only 3% of web sites incorrectly stated that IUDs are an abortifacient. More than a quarter of sites listed an inaccurate contraindication to the IUD such as nulliparity, history of pelvic inflammatory disease, or history of an ectopic pregnancy. CONCLUSION: The quality of information about IUDs available on the Internet is variable. Accurate information was mixed with inaccurate or outdated information that could perpetuate myths about IUDs. Clinicians need knowledge about accurate, evidence-based Internet resources to provide to women given the inconsistent quality of information available through online sources. PMID- 26546849 TI - Evaluation of trainees' ability to perform obstetrical ultrasound using simulation: challenges and opportunities. AB - BACKGROUND: Evaluation of trainee's ability in obstetrical ultrasound is a time consuming process, which requires involving patients as volunteers. With the use of obstetrical ultrasound simulators, virtual reality could help in assessing competency and evaluating trainees in this field. OBJECTIVE: The objective of the study was to test the validity of an obstetrical ultrasound simulator as a tool for evaluating trainees following structured training by comparing scores obtained on obstetrical ultrasound simulator with those obtained on volunteers and by assessing correlations between scores of images and of dexterity given by 2 blinded examiners. STUDY DESIGN: Trainees, taking the 2013 French national examination for the practice of obstetrical ultrasound were asked to obtain standardized ultrasound planes both on volunteer pregnant women and on an obstetrical ultrasound simulator. These planes included measurements of biparietal diameter, abdominal circumference, and femur length as well as reference planes for cardiac 4-chamber and outflow tracts, kidneys, stomach/diaphragm, spine, and face. Images were stored and evaluated subsequently by 2 national examiners who scored each picture according to previously established quality criteria. Dexterity was also evaluated and subjectively scored between 0 and 10. The Raghunathan's modification of Pearson, Filon's z, Spearman's rank correlation, and analysis of variance tests were used to assess correlations between the scores by the 2 examiners and scores of dexterity and also to compare the final scores between the 2 different methods. RESULTS: We evaluated 29 trainees. The mean dexterity scores in simulation (6.5 +/- 2.0) and real examination (5.9 +/- 2.3) were comparable (P = .31). Scores with an obstetrical ultrasound simulator were significantly higher than those obtained on volunteers (P = .027). Nevertheless, there was a good correlation between the scores of the 2 examiners judging on simulation (R = 0.888) and on volunteers (R = 0.873) (P = .81). CONCLUSION: An obstetrical ultrasound simulator is as good a method as volunteer-based examination for evaluating practical skills in trainees following structured training in obstetrical ultrasound. The threshold for success/failure should, however, be adapted as candidates obtain higher scores on the simulator. Advantages of the obstetrical ultrasound simulator include the absence of location and time constraints without the need to involve volunteers or to interfere with the running of ultrasound clinics. However, an obstetrical ultrasound simulator still lacks the ability to evaluate the trainees' ability to interact with patients. PMID- 26546850 TI - INTERGROWTH-21st vs customized birthweight standards for identification of perinatal mortality and morbidity. AB - BACKGROUND: The recently published INTERGROWTH-21st Project international population standard for newborn size is intended for global use, but its ability to identify small infants at risk of adverse outcomes in a general obstetric population has not been reported. OBJECTIVE: The objective of the study was to compare adverse neonatal outcomes among small-for-gestational-age (SGA) infants between the INTERGROWTH-21st standard and a customized birthweight standard (accounting for maternal characteristics of height, weight, parity, and ethnicity). We hypothesized that in a multiethnic general obstetric population in Auckland, New Zealand, a customized birthweight standard would better identify SGA infants at-risk of neonatal morbidity/mortality and stillbirth than the INTERGROWTH-21st standard. STUDY DESIGN: Using prospectively gathered maternity data from a general obstetric population in Auckland, New Zealand, from 2006 to 2013 (n = 53,484 births at >= 33 weeks), infants were classified as SGA (birthweight < 10th centile) by INTERGROWTH-21st and customized standards. Infants were further categorized as SGA by both criteria, INTERGROWTH-21st only, customized only, or not SGA (met neither criteria). Composite adverse neonatal outcome was defined as neonatal death, neonatal intensive care admission > 48 hours, or ventilation > 4 hours or 5-minute Apgar score < 7. Relative risks for primary outcomes were estimated using modified Poisson regression, with the non SGA group as the referent. RESULTS: Incidence of SGA was 4.5% by INTERGROWTH-21st and 11.6% by customized standard. Compared with those not SGA, infants identified as small for gestational age by both criteria had the highest risk of adverse neonatal outcome (relative risk [RR], 4.1, 95% confidence interval [CI], 3.7-4.6) and stillbirth (RR, 8.3, 95% CI, 5.1-13.4). Infants SGA by customized standard only (n = 4015) had an increased risk of adverse neonatal outcome (RR, 2.0, 95% CI, 1.8-2.2) and stillbirth (RR, 3.0, 95% CI, 1.7-5.3). Few infants were identified as SGA by INTERGROWTH-21st only (n = 172), and risks of adverse neonatal outcome and stillbirth were not increased. Findings were unchanged when analyses were limited to term infants (n = 50,739). The INTERGROWTH-21st standard identified more Indian (12.8%) and Asian (5.8%) but fewer European (3.0%) and Pacific (2.9%) infants as SGA (P < .01). Customized criteria identified more than 3 times as many SGA infants among Maori (14.5%), Pacific (13.5%), and European (11.2%) infants and twice as many among Asian (10.3%) infants (P<0.01) compared with INTERGROWTH-21st criteria. The majority of SGA infants by INTERGROWTH-21st only were born to Indian and Asian mothers (95.4%). CONCLUSIONS: In our general obstetric population, birthweight customization identified more SGA infants at risk of perinatal mortality and morbidity compared with the INTERGROWTH-21st standard. The INTERGROWTH-21st standard failed to detect many at-risk SGA infants, particularly among ethnic groups with larger maternal size while disproportionately identifying higher rates of SGA among those with smaller maternal size. Local validation is needed prior to implementation of the INTERGROWTH-21st standard to avoid misclassification of infant birth size. PMID- 26546851 TI - Pregnancy among US women: differences by presence, type, and complexity of disability. AB - BACKGROUND: Approximately 12% of women of reproductive age have some type of disability. Very little is known about sexual and reproductive health issues among women with disabilities, including what proportion of women with disabilities experience pregnancy. Data on pregnancy are important to inform needs for preconception and pregnancy care for women with disabilities. OBJECTIVE: The purpose of this study was to describe the occurrence of pregnancy among women with various types of disability and with differing levels of disability complexity, compared with women without disabilities, in a nationally representative sample. STUDY DESIGN: We conducted cross-sectional analyses of 2008-2012 Medical Expenditure Panel Survey annualized data to estimate the proportion of women aged 18-44 years with and without disabilities who reported a pregnancy during 1 year of participation on the survey panel. We used a multivariable logistic regression to test the association of pregnancy with presence, type, and complexity of disability, controlling for other factors associated with pregnancy. RESULTS: Similar proportions of women with and without disabilities reported a pregnancy (10.8% vs 12.3%, with 95% confidence intervals overlapping). Women with the most complex disabilities (those that impact activities such as self-care and work) were less likely to have been pregnant (adjusted odds ratio, 0.69, 95% confidence interval, 0.52-0.93), but women whose disabilities affected only basic actions (seeing, hearing, movement, cognition) did not differ significantly from women with no disabilities. CONCLUSION: Women with a variety of types of disabilities experience pregnancy. Greater attention is needed to the reproductive health care needs of this population to ensure appropriate contraceptive, preconception, and perinatal care. PMID- 26546852 TI - Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain. AB - BACKGROUND: Advances in surgery and technology have resulted in increased in utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. OBJECTIVE: The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. STUDY DESIGN: Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% * 1 hour, 4% * 3 hours, or 2% * 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. RESULTS: A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2% isoflurane exposure compared to controls (1.57 +/- 0.22 * 10(6)/mm(3) vs 1.01 +/- 0.44 * 10(6)/mm(3), P = .02). Fetuses at 70 days gestation with repeated exposure demonstrated decreased frontal cortex neurons at day 130 when compared to age matched controls (2.42 +/- 0.3 * 10(5)/mm(3) vs 7.32 +/- 0.4 * 10(5)/mm(3), P = .02). No significant difference in neuroapoptosis was observed between the repeated exposure group and controls in the hippocampus, cerebellum, or basal ganglia. CONCLUSION: Repeated isoflurane exposure in midgestation sheep resulted in increased frontal cortex neuroapoptosis. This persisted into late gestation as decreased neuronal cell density. While animal studies should be extrapolated to human beings with caution, our findings suggest that the number of anesthetic/sedative exposures should be considered when contemplating the risks and benefits of fetal intervention as certain fetal therapies may need to be repeated. PMID- 26546853 TI - Screening for carbapenemase-producing Enterobacteriaceae-issues for consideration. PMID- 26546854 TI - The epidemiological characteristics and genetic diversity of dengue virus during the third largest historical outbreak of dengue in Guangdong, China, in 2014. AB - OBJECTIVES: The third largest historical outbreak of dengue occurred during July to December 2014, in 20 of 21 cities of Guangdong, China. The epidemiological and molecular characteristics of the introduction, expansion and phylogeny of the DENV isolates involved in this outbreak were investigated. METHODS: A combination analyses of epidemiological characteristics and genetic diversity of dengue virus was performed in this study. RESULTS: In total, 45,236 cases and 6 fatalities were reported. Unemployed individuals, retirees and retailers were the most affected populations. A total of 6024 cases were verified to have DENV infections by nucleic acid detection, of which 5947, 74 and 3 were confirmed to have DENV-1, -2, and -3 infections, respectively. Phylogenetic analyses of DENV-1 isolates were assigned into three genotypes (I, IV, and V). Genotype V was the predominant genotype that likely originated from Singapore. The DENV-2 isolates were assigned to the Cosmopolitan and Asian I genotypes. A unique DENV-3 isolate (genotype III) shared high similarity with isolates obtained from Guangdong in 2013. CONCLUSIONS: A combination analyses demonstrated the multiple geographical origins of this outbreak, and highlight the importance of early detection, the case management and vector surveillance for preventing further dengue epidemics in Guangdong. PMID- 26546856 TI - Urban/Rural Differences in Therapy Service Use Among Medicaid Children Aged 0-3 With Developmental Conditions in Colorado. AB - OBJECTIVE: To describe urban/rural differences in physical (PT) and occupational therapy (OT) service utilization and spending among a sample of young Medicaid enrolled children with developmental conditions. METHODS: We analyzed Colorado Children's Medicaid administrative claims from 2006 to 2008. The sample included children who were younger than 36 months of age, had a select developmental condition, and were continuously eligible for each study year up to their third birthday. The study outcomes were number of PT/OT claims, type of PT/OT service, and Medicaid PT/OT spending. Multivariable analyses examined urban/rural differences in PT/OT utilization and spending, adjusting for child, family, and health service characteristics. RESULTS: The sample included 20,959 children. In adjusted analyses, urban children had 2-fold higher odds (odds ratio 2.18, 95% confidence interval 1.89, 2.51) of receiving PT/OT compared to their rural peers. Median annual per-child Medicaid PT/OT spending was $99 higher ($98.79 [$3.23, $194.35]) for urban children versus rural children. When place of PT/OT service and PT/OT procedures was included, this spending difference was drastically reduced. CONCLUSIONS: Even accounting for child, family, and health service characteristics, Medicaid PT/OT spending is lower for rural children compared to their urban peers. The difference in spending is largely attributable to utilization of services that are less specialized than urban peers, thus suggesting disparities in access to appropriate PT/OT services. PMID- 26546857 TI - Mineral homeostasis and regulation of mineralization processes in the skeletons of sharks, rays and relatives (Elasmobranchii). AB - Sharks, rays and other elasmobranch fishes are characterized by a skeletal type that is unique among living vertebrates, comprised predominantly of an unmineralized cartilage, covered by a thin outer layer of sub-millimeter, mineralized tiles called tesserae. The mineralized portion of the skeleton appears to grow only by apposition, adding material at the edges of each tessera; maintenance of non-mineralized joints between tesserae is therefore vital, with precise control of mineral deposition and inhibition at the many thousands of growth fronts in the skeleton. Yet, we have only scattered evidence as to how the elasmobranchs mineralize and grow their skeletons. In this review, we take an "environment to skeleton" approach, drawing together research from a vast range of perspectives to track calcium and phosphate from the typical elasmobranch habitats into and through the body, to their deposition at tesseral growth fronts. In the process, we discuss the available evidence for skeletal resorption capability, mineral homeostasis hormones, and nucleation inhibition mechanisms. We also outline relevant theories in crystal nucleation and typical errors in measurements of serum calcium and phosphate in the study of vertebrate biology. We assemble research that suggests consensus in some concepts in elasmobranch skeletal development, but also highlight the very large gaps in our knowledge, particularly in regards to endocrine functional networks and biomineralization mechanisms. In this way, we lay out frameworks for future directions in the study of elasmobranch skeletal biology with stronger and more comparative links to research in other disciplines and into other taxa. PMID- 26546858 TI - Bridging the translational gap: collaborative drug development and dispelling the stigma of commercialization. AB - The current drug discovery and development process is stalling the translation of basic science into lifesaving products. Known as the 'Valley of Death', the traditional technology transfer model fails to bridge the gap between early-stage discoveries and preclinical research to advance innovations beyond the discovery phase. In addition, the stigma associated with 'commercialization' detracts from the importance of efficient translation of basic research. Here, I introduce a drug discovery model whereby the respective expertise of academia and industry are brought together to take promising discoveries through to proof of concept as a way to derisk the drug discovery and development process. Known as the 'integrated drug discovery model', I examine here the extent to which existing legal frameworks support this model. PMID- 26546855 TI - Comprehensive clinical and epidemiological assessment of colonisation and infection due to carbapenemase-producing Enterobacteriaceae in Spain. AB - BACKGROUND: Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain. METHODS: A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality. RESULTS: Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-beta-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and healthcare-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR = 3.30; 95% CI: 1.34-8.11). CONCLUSIONS: We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality. PMID- 26546859 TI - Natural polyphenols: potential in the prevention of sexually transmitted viral infections. AB - Sexually transmitted viral infections represent a major public health concern due to lack of effective prevention strategies. Efforts are ongoing to develop modalities that can enable simultaneous prevention of multiple sexually transmitted infections. In the present review, we discuss the potential of natural polyphenols to prevent sexually transmitted viral infections. The review gives an account of various in vitro and in vivo studies carried out on epigallocatechin gallate, theaflavins (black tea polyphenols), resveratrol, genistein and curcumin to highlight their potential to prevent sexually transmitted infections caused by HIV (human immunodeficiency virus), HSV (herpes simplex virus) and HPV (human papilloma virus). PMID- 26546860 TI - Psychophysiological science and the research domain criteria: A commentary. AB - The current special issue, devoted to the Research Domain Criteria (RDoC) initiative of the US National Institute of Mental Health, showcases a variety of empirical and review articles that address issues related to this dimensional and multi-method approach to research on mental disorders. Here, we provide an integrative perspective on various aspects of these articles, focused around the primary principles of the RDoC approach and the practical and methodological issues related to conducting RDoC-informed research. The chief point we wish to highlight is that these articles demonstrate the ways in which the field of psychophysiology already thinks along the lines of RDoC in terms of using biobehavioral constructs, looking for convergence among constructs using various methodologies, and utilizing dimensional measurements in studies. In this sense, RDoC is not novel; however, by specifying a formal research platform it provides explicit encouragement and guidance for using such principles in understanding psychiatric phenomena, rather than continuing to focus research efforts on traditional diagnostic categories alone. PMID- 26546861 TI - Situating psychophysiological science within the Research Domain Criteria (RDoC) framework. AB - The Research Domain Criteria (RDoC) reflects a paradigm shift in mental health research aimed at establishing a science of psychopathology that is grounded in neuroscience. In many ways, the RDoC approach to research has been utilized for decades by psychophysiologists who have leveraged a range of biological measures to study variability in psychological processes as a function of individual differences. We highlight the critical role of psychophysiology in the era of RDoC, and briefly review the 13 papers and commentary that form the current special issue. PMID- 26546862 TI - The Virtual Tray of Objects Task as a novel method to electrophysiologically measure visuo-spatial recognition memory. AB - We explored a novel method to electrophysiologically measure visuo-spatial recognition memory using a modified version of the Virtual Tray of Objects Task (VTOT). Event-related potentials (ERP) were recorded from 18 healthy volunteers during performance in the VTOT. Participants were required to detect random repetitions of three-dimensional visual stimuli (OLD) and to refrain from responding to non-repeated stimuli (NEW). Differences in ERP between the NEW and OLD conditions were tested for statistical significance using assumption-free non parametric analyses. Further, a correlation between ERP and behavioral measures was sought. Significant OLD-NEW effects were found for four ERP components showing distinct spatio-temporal characteristics: a posterior positive component appearing at 100 ms (P100), a left-lateralized negative component peaking at ~250 ms (N250), a frontal negative component at ~300-450 ms (FN400), and a right late frontal negativity (rLFN) at ~500-720 ms. Moreover, individual differences in the OLD-NEW effect computed for the rLFN positively correlated with repeated stimulus recognition efficiency. However, there were no late left parietal P600 old/new effects. These findings suggest that the P100 component might reflect early visual perception processes taking place during performance in the task, whereas the N250 and FN400 components could be linked to stimulus-dependent access to visual memory representations and familiarity-related processes, respectively. In contrast, we propose that the rLFN component could be associated with higher level cognitive functions, such as attention and monitoring processes. Altogether, our results suggest that the ERP version of the VTOT could play a role in the electrophysiological assessment of visuo-spatial memory and related sub-processes. PMID- 26546863 TI - State space modeling of time-varying contemporaneous and lagged relations in connectivity maps. AB - Most connectivity mapping techniques for neuroimaging data assume stationarity (i.e., network parameters are constant across time), but this assumption does not always hold true. The authors provide a description of a new approach for simultaneously detecting time-varying (or dynamic) contemporaneous and lagged relations in brain connectivity maps. Specifically, they use a novel raw data likelihood estimation technique (involving a second-order extended Kalman filter/smoother embedded in a nonlinear optimizer) to determine the variances of the random walks associated with state space model parameters and their autoregressive components. The authors illustrate their approach with simulated and blood oxygen level-dependent functional magnetic resonance imaging data from 30 daily cigarette smokers performing a verbal working memory task, focusing on seven regions of interest (ROIs). Twelve participants had dynamic directed functional connectivity maps: Eleven had one or more time-varying contemporaneous ROI state loadings, and one had a time-varying autoregressive parameter. Compared to smokers without dynamic maps, smokers with dynamic maps performed the task with greater accuracy. Thus, accurate detection of dynamic brain processes is meaningfully related to behavior in a clinical sample. PMID- 26546864 TI - Neural signatures of hand kinematics in leaders vs. followers: A dual-MEG study. AB - During joint actions, people typically adjust their own actions according to the ongoing actions of the partner, which implies that the interaction modulates the behavior of both participants. However, the neural substrates of such mutual adaptation are still poorly understood. Here, we set out to identify the kinematics-related brain activity of leaders and followers performing hand actions. Sixteen participants as 8 pairs performed continuous, repetitive right hand opening and closing actions with ~3-s cycles in a leader-follower task. Subjects played each role for 5min. Magnetoencephalographic (MEG) brain signals were recorded simultaneously from both partners with a dual-MEG setup, and hand kinematics was monitored with accelerometers. Modulation index, a cross-frequency coupling measure, was computed between the hand acceleration and the MEG signals in the alpha (7-13Hz) and beta (13-25Hz) bands. Regardless of the participants' role, the strongest alpha and beta modulations occurred bilaterally in the sensorimotor cortices. In the occipital region, beta modulation was stronger in followers than leaders; these oscillations originated, according to beamformer source reconstructions, in early visual cortices. Despite differences in the modulation indices, alpha and beta power did not differ between the conditions. Our results indicate that the beta modulation in the early visual cortices depends on the subject's role as a follower or leader in a joint hand-action task. This finding could reflect the different strategies employed by leaders and followers in integrating kinematics-related visual information to control their own actions. PMID- 26546865 TI - GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion. AB - In everyday life we are confronted with inputs of multisensory stimuli that need to be integrated across our senses. Individuals vary considerably in how they integrate multisensory information, yet the neurochemical foundations underlying this variability are not well understood. Neural oscillations, especially in the gamma band (>30Hz) play an important role in multisensory processing. Furthermore, gamma-aminobutyric acid (GABA) neurotransmission contributes to the generation of gamma band oscillations (GBO), which can be sustained by activation of metabotropic glutamate receptors. Hence, differences in the GABA and glutamate systems might contribute to individual differences in multisensory processing. In this combined magnetic resonance spectroscopy and electroencephalography study, we examined the relationships between GABA and glutamate concentrations in the superior temporal sulcus (STS), source localized GBO, and illusion rate in the sound-induced flash illusion (SIFI). In 39 human volunteers we found robust relationships between GABA concentration, GBO power, and the SIFI perception rate (r-values=0.44 to 0.53). The correlation between GBO power and SIFI perception rate was about twofold higher when the modulating influence of the GABA level was included in the analysis as compared to when it was excluded. No significant effects were obtained for glutamate concentration. Our study suggests that the GABA level shapes individual differences in audiovisual perception through its modulating influence on GBO. GABA neurotransmission could be a promising target for treatment interventions of multisensory processing deficits in clinical populations, such as schizophrenia or autism. PMID- 26546866 TI - Polysaccharopeptide exerts immunoregulatory effects via MyD88-dependent signaling pathway. AB - AIMS: The present study is to investigate the immunomodulatory mechanism and related pathways of polysaccharopeptide (PSP) in mice bearing Ehrlich's ascites carcinoma (EAC). METHODS: Twelve female wild-type C57 mice were randomly divided into three groups. Another twelve female myeloid differentiation factor 88 (MyD88)-deficient mice were randomly assigned to three groups. Cell survival and peritoneal macrophage phagocytosis were measured using WST8 assay. Nitric oxide concentration was determined by Griess reaction. ELISA was used to measure tumor necrosis factor-alpha and interferon-gamma levels. Quantitative real-time PCR was employed to measure mRNA levels. Western blotting was performed to determine protein expression. RESULTS: PSP significantly inhibited the proliferation of EAC cells via macrophage activation. PSP-primed macrophages exhibited a higher tumoricidal activity than untreated macrophages. PSP markedly inhibited the growth of the tumor and increased macrophage phagocytosis, nitric oxide release and cytokine secretion. Expression of MyD88 was markedly increased in PSP-treated groups, while ST2825 inhibited MyD88 signaling and interfered with nitric oxide release and the secretion of tumor necrosis factor-alpha and interferon-gamma. Moreover, mRNA and protein levels associated with MyD88-dependent signaling pathway in MyD88-deficient mice group were significantly down-regulated compared with wild-type mice group. CONCLUSIONS: PSP plays an immunoregulatory effect through MyD88-dependent signaling pathway. PMID- 26546867 TI - An exopolysaccharide isolated from a coral-associated fungus and its sulfated derivative activates macrophages. AB - A coral-associated fungus Penicillium sp.gxwz446 that produced exopolysaccharde was isolated from the coral Echinogorgia flora in South China. Two neutral exopolysaccharides GX1-1 and GX2-1 were obtained from the fermented broth of the fungus and purified by anion-exchange and gel-permeation chromatography. Chemical and spectroscopic analyses showed that GX1-1 was a glucan, primarily composed of glucose, with a molecular weight of 5.0 kDa. GX1-1 mainly consists of (1->4) linked alpha-d-glucopyranose units as the backbone, substituted at C-2 with a single alpha-d-glucopyranose on every sixth sugar residues. GX2-1 was a galactofuranose-containing mannogalactoglucan with a molecular weight of 9.5 kDa. The main linkages were composed of (1->4)-beta-d-Glcp, (1->5)-beta-d-Galf, (1 >3,5)-beta-d-Galf, (1->6)-alpha-d-Manp and (1->2, 6)-alpha-d-Manp. GX1-1 showed RAW264.7 macrophage activation activity. After subjecting GX1-1 to sulfated modification, there was about one sulfate substitution on every sugar ring, primarily at O-6. The sulfated derivative of GX1-1 exhibited a more significant ability to promote the pinocytic activity of RAW264.7 cells and induce the production of NO. PMID- 26546868 TI - Removal of direct dyes from aqueous solution by oxidized starch cross-linked chitosan/silica hybrid membrane. AB - In this research, chitosan/oxidized starch/silica (CS/OSR/Silica) hybrid membrane was prepared by using oxidized starch and 3-aminopropyltriethoxysilane (APTES) as cross-linking agents. The characterizations of the hybrid membrane were investigated by using attenuated total reflection (ATR) spectroscopy, scanning electron microscopy (SEM), thermogravimetry (TG) analysis and swelling measurement. The CS/OSR/Silica hybrid membrane exhibited the improved thermal stability and low degree of swelling in water. The adsorption properties of the CS/OSR/Silica hybrid membrane were studied by using two direct dyes (Blue 71 and Red 31). The results indicated the adsorption capacity of the CS/OSR/Silica hybrid membrane was found optimal at pH 9.82 and temperature 60 degrees C for Blue 71 and Red 31. The adsorption kinetic data followed pseudo-second order kinetic model and the adsorption behavior of the two dyes on the hybrid membrane fitted well with the Freundlich model. The CS/OSR/Silica hybrid membrane can be used as an appropriate biosorbent for removal of direct dyes from colored wastewater. PMID- 26546869 TI - Sodium lignosulfonate as a renewable stabilizing agent for aqueous alumina suspensions. AB - The macromolecule sodium lignosulfonate (SL) has been investigated as dispersing agent for aqueous alumina colloids as a renewable alternative to usual petrochemical stabilizing agents. Optimization of the SL concentration necessary to stabilize the alumina suspension at different pH values was determined by viscometer. The results showed that addition of 250 ppm of the total suspension mass led to about 70% viscosity reduction of the suspension, whereas zeta potential analysis revealed negative values for the SL suspensions throughout the pH range investigated, suggesting that the alumina particles were covered by negatively charged SL molecules. Particle size investigation informed that the average particle diameter of the SL suspensions was smaller compared to that of the pristine particles. Sedimentation time for the SL suspensions was dramatically longer than that for the pristine one. The reported data strongly corroborated that SL is a suitable renewable dispersing agent for aqueous alumina colloids. PMID- 26546870 TI - Durable antibacterial and UV protections of in situ synthesized zinc oxide nanoparticles onto cotton fabrics. AB - Herein we represent a new discovery based on amine material called hexamethyltriethylene tetramine (HMTETA). We have observed that when an aqueous solution of Zn(NO3).6H2O was added to aqueous solution of HMTETA followed by shaking for a time, the colorless solution was converted to milky color under the alkaline medium provided by HMTETA prior to formation of uniform zinc oxide nanoparticles (ZnO NPs). The latter are in situ formed within the cotton fabrics without the support of capping or other stabilizing agents. Obviously, then, the new made of formation of ZnO NPs speaks of a single-stage process where cotton fabric is immersed in a prepared solution of the new precursors through which binding of ZnO NPs into the textile fabrics takes place. Textile fabrics are, indeed, used as a template, which is capable of maintaining the size and surface distribution of the as-synthesized nanoparticles in a uniform domain. It is also likely that nanoparticles is confined inside the fibril and microfibrils of the cotton fibers. World-class facilities have been employed to follow up the synthesis of ZnO NPs, their characterization and their application to confer, in particular, high durable antibacterial and UV protective function on cotton fabrics. PMID- 26546871 TI - Significant growth of adrenal lymphangioma: A case report and review of the literature. AB - INTRODUCTION: Adrenal lymphangiomas are benign malformations of lymphatic vessels of adrenal gland. Adrenal lymphangiomas are very rare, although lymphangiomas are most commonly located in the neck, axillary region and mediastinum. PRESENTATION OF CASE: A 44-year-old woman presented to the outpatient clinic with dizziness, headache during the last 2 year. We report a significant growth case of an adrenal lymphangioma removed by transperitoneal laparoscopy. At laparoscopy, a well-marginated multicystic lesion was found at suprarenal area with nonviscous, brown colored fluid. The cystic mass was measured as 5.5*3.0cm and histopathological diagnosis was cystic lymphangioma in the right adrenal gland. On immunohistochemical examination, D2-40 cytoplastic staining was positive, whereas calretinin and CD34 were negative, thus, confirming their lymphatic nature. At 11 months of follow up, the patient was recurrence free. DISCUSSION: Lymphangiomas are benign malformations of lymphatic vessels and subtype of endothelial adrenal cysts. Adrenal cysts are histologically classified into four main groups: endothelial cysts (45%), pseudocysts (39%), epithelial cysts (9%), and parasitic cysts (7%). Endothelial cysts are divided into two subgroups: lymphangiomatous and angiomatous cysts. Lymphangiomatous adrenal cysts are also known as adrenal lymphangioma. Management of larger lesions or lesions causing symptoms may require surgical resection to determine diagnosis or relieve symptoms. CONCLUSION: Lymphangiomas are most commonly located in the neck, axillary region and mediastinum, which are rare at adrenal gland. Transperitoneal laparoscopic removal of the adrenal lymphangiomas is regarded as a safe, effective and minimally invasive approach. In our case, laparoscopic removal of the tumor was successfully performed via a transperitoneal approach. PMID- 26546872 TI - Metabolic exchanges within tumor microenvironment. AB - Tumor progression toward malignancy often requires a metabolic rewiring of cancer cells to meet changes in metabolic demand to forefront nutrient and oxygen withdrawal, together with strong anabolic requests to match high proliferation rate. Tumor microenvironment highly contributes to metabolic rewiring of cancer cells, fostering complete nutrient exploitation, favoring OXPHOS of lipids and glutamine at the expense of glycolysis and enhancing exchanges via extracellular microvesicles or exosomes of proteins, lipids and small RNAs among tumor and stromal cells. Noteworthy, the same molecular drivers of metabolic reprogramming within tumor and stroma are also able to elicit motility, survival and self renewal on cancer cells, thereby sustaining successful escaping strategies to circumvent the hostile hypoxic, acidic and inflammatory environment. This review highlights the emerging role of nutrients and vesicle-mediated exchanges among tumor and stromal cells, defining their molecular pathways and offering new perspectives to develop treatments targeting this complex metabolic rewiring. PMID- 26546873 TI - HLA Haplotype Validator for quality assessments of HLA typing. AB - HLA alleles are observed in specific haplotypes, due to Linkage Disequilibrium (LD) between particular alleles. Haplotype frequencies for alleles in strong LD have been established for specific ethnic groups and racial categories. Application of high-resolution HLA typing using Next Generation Sequencing (NGS) is becoming a common practice in research and clinical laboratory settings. HLA typing errors using NGS occasionally occur due to allelic sequence imbalance or misalignment. Manual inspection of HLA genotypes is labor intensive and requires an in-depth knowledge of HLA alleles and haplotypes. We developed the "HLA Haplotype Validator (HLAHapV)" software, which inspects an HLA genotype for both the presence of common and well-documented alleles and observed haplotypes. The software also reports warnings when rare alleles, or alleles that do not belong to recognized haplotypes, are found. The software validates observable haplotypes in genotype data, providing increased confidence regarding the accuracy of the HLA typing, and thus reducing the effort involved in correcting potential HLA typing errors. The HLAHapV software is a powerful tool for quality control of HLA genotypes prior to the application of downstream analyses. We demonstrate the use of the HLAHapV software for identifying unusual haplotypes, which can lead to finding potential HLA typing errors. PMID- 26546874 TI - Sialylation of antibodies in kidney recipients with de novo donor specific antibody, with or without antibody mediated rejection. AB - BACKGROUND: DSA are associated with reduced long-term transplant function and increased prevalence of chronic rejection in some patients, whereas others do not: our goal was to determine whether the sialylation of IgG and DSA could help to explain in these last cases their "non-aggressive" and/or "protective" biological activity. METHODS: The sialylation level of total IgG in blood from two groups of kidney-transplant patients with de novo DSA, one with an AMR (DSA+AMR+), and the other without were studied. RESULTS: In the DSA+AMR- patients total IgG were more sialylated at time of transplant, and at the first detection of DSA, class I DSA were 2.6-fold more sialylated (mean 9.943+/-1.801 versus 3.898+/-2.475, p=0.058); DSA+AMR+ patients exhibited higher levels of class II DSA. CONCLUSIONS: In our study, higher levels of sialylated IgG are detectable on day of transplant in patients who do not develop AMR, they have higher sialylated class I DSA at the initial detection of DSA, whereas class II DSA are significantly higher in patients who develop AMR. This is the first report suggesting that transplant outcome, and particularly AMR, is associated with levels of sialylated IgG antibodies. Our data suggest that DSA are functionally heterogeneous and that further studies with an enlarged cohort may improve our understanding of their clinical impact. PMID- 26546875 TI - Dual inhibition of nuclear factor kappa-B and Mdm2 enhance the antitumor effect of radiation therapy for pancreatic cancer. AB - INTRODUCTION: Radiation therapy, alone or in combination with chemotherapy, is effective for patients with locally advanced and recurrent pancreatic cancer. Ionizing radiation induces cell cycle arrest and cell apoptosis through enhancement several signals such as p53, p21(Waf1/Cip1), and caspase. However, the therapeutic efficacy is attenuated by radiation-induced activation of NF kappaB. Nafamostat mesilate, a synthetic serine protease inhibitor, inhibits NF kappaB activation in pancreatic cancer. Therefore, we hypothesized that nafamostat mesilate inhibited radiation-induced activation of NF-kappaB and improves therapeutic outcome. RESULTS: In combination group, NF-kappaB activation was significantly inhibited in comparison with that of radiation group. Nafamostat mesilate obviously down-regulated the expression levels of Mdm2 compared with control cells or irradiated cells. Consequently, p53 expression was stabilized inversely in correlation with Mdm2 protein expression level. The expression levels of p53, p21(Waf1/Cip1), cleaved caspase-3 and -8 were the highest in the combination group. Nafamostat mesilate enhanced ionizing radiation induced cell apoptosis and G2/M cell cycle arrest. In combination group, cell proliferation and tumor growth were significantly slower than those in other groups. CONCLUSION: Combination therapy of radiation with nafamostat mesilate exerts enhanced anti-tumor effect against human pancreatic cancer. PMID- 26546876 TI - Simultaneous influenza A and B infection in a pregnant woman in the context of influenza A family cluster. PMID- 26546877 TI - The impact of calicivirus mixed infection in an oyster-associated outbreak during a food festival. AB - BACKGROUND: Despite calicivirus food-borne outbreaks posing major public health concern worldwide, little information is at present available about the impact of caliciviruses mixed infection in an oyster-associated outbreak in China. OBJECTIVES: To investigate the clinical and epidemiologic characteristics of an oyster-associated calicivirus outbreak initiated by a food festival in Shanghai, China, in April 2014. STUDY DESIGN: Molecular epidemiological studies based on nucleotide sequencing and phylogenetic analysis of calicivirus strains from patients. RESULTS: A total of 65 of the 78 (83%) cases from this outbreak were associated with raw oyster consumption. Forty-six calicivirus strains were identified from 25 stool specimens with norovirus (NoV) GII.4 Sydney_2012, GII.13, GI.2, GI.5 and sapovirus (SaV) GI.2 being predominant genotypes and with a prevalence of triple-, double- and single-infection being 20%, 48% and 28%, respectively. Meanwhile, 13 putative NoV recombinants were indicated by the phylogenetic inconsistency between capsid and polymerase genotype, mainly including GII.Pe/GII.4 Sydney_2012. Molecular epidemiological investigation showed possible multiple route transmission in the field. The clinical and epidemiologic characteristics of the mixed point-source calicivirus outbreak also conformed to Kaplan's criteria. CONCLUSIONS: This is the first reported oyster associated calicivirus outbreak with a high prevalence of mixed infection during a food festival described in China. Our investigation underscores the importance of early surveillance and comprehensive etiologic identification of mixed point source outbreaks and the need for reliable standards of monitoring oysters to prevent and control calicivirus food-borne outbreaks in China. PMID- 26546878 TI - Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide based chemotherapy. AB - BACKGROUND: The incidence of herpes zoster is substantial during bortezomib treatment in patients with multiple myeloma (MM). OBJECTIVES: This study aimed to elucidate the effect of chemotherapy with or without bortezomib in MM patients on their herpes zoster incidence and varicella zoster virus (VZV)-specific cell mediated immunity (CMI). STUDY DESIGN: Peripheral blood mononuclear cells were collected at baseline and after 1 month of bortezomib-based or thalidomide-based chemotherapy and then analyzed using VZV-specific interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay. The clinical data from these patients were analyzed in relation to the ELISPOT results. RESULTS: Of 58 patients analyzed, 39 patients received bortezomib and the other 19 patients, thalidomide. Among them, 5 patients developed herpes zoster during chemotherapy; all 5 were being treated with the bortezomib-based regimen and were not receiving prophylactic anti-viral agents. The median onset of herpes zoster was 32 days (range, 15-95 days) from the initiation of chemotherapy. Among patients who received bortezomib therapy, acyclovir prophylaxis significantly reduced the risk for herpes zoster (100-day cumulative incidence, 0% vs. 49.5%; p<0.001). Spot forming cell (SFC) counts in the IFN-gamma ELISPOT assay decreased from baseline after bortezomib (p=0.011) or thalidomide (p=0.096) treatment. Patients with baseline SFCs greater than 20/10(6) mononuclear cells exhibited significantly higher incidence of herpes zoster (100-day cumulative incidence, 34.8% vs. 0%; p=0.040). CONCLUSIONS: Bortezomib treatment significantly reduced VZV-specific CMI, and high baseline SFC counts in patients receiving this treatment without acyclovir prophylaxis were associated with a significantly increased risk for herpes zoster. PMID- 26546879 TI - Youth is not wasted on the young: Commentary on a BBR themed issue on developmental regulation of memory in anxiety and addiction. PMID- 26546880 TI - A novel turning behavior control method for rat-robot through the stimulation of ventral posteromedial thalamic nucleus. AB - The concept of a rat-robot was initially introduced in 2002, bringing to the field, a novel area of research using modern research into neuroscience and robotics. This paper brings to the table, a study into the method best used for navigation systems in a rat-robot. Current research is epitomized by the use of reward-based spatial navigation, combining the concept of an induced reward sensation as well as a 'virtual touch' sensation to control the movement of the rat-robot. However, such methods are plagued by limitations affecting the success rate as well as preparation procedures which may have varying effects on different rats, even under similar conditions. Hence, this paper studies the stimulation of two different portions of the brain to induce a turning motion within the rat, namely the Ventral Posteromedial (VPM) thalamic nucleus as well as the Barrel-Field (BF) cortex and demonstrates the preferential usage of VPM as the choice use of navigational control in a rat-robot. PMID- 26546881 TI - Effect of omega-3 polyunsaturated fatty acid treatment over mechanical allodynia and depressive-like behavior associated with experimental diabetes. AB - Neuropathic pain and depression are very common comorbidities in diabetic patients. As the pathophysiological mechanisms are very complex and multifactorial, current treatments are only symptomatic and often worsen the glucose control. Thus, the search for more effective treatments are extremely urgent. In this way, we aimed to investigate the effect of chronic treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, over the mechanical allodynia and in depressive-like behaviors in streptozotocin-diabetic rats. It was observed that the diabetic (DBT) animals, when compared to normoglycemic (NGL) animals, developed a significant mechanical allodynia since the second week after diabetes induction, peaking at fourth week which is completely prevented by FO treatment (0.5, 1 or 3g/kg). Moreover, DBT animals showed an increase of immobility frequency and a decrease of swimming and climbing frequencies in modified forced swimming test (MFST) since the second week after diabetes injection, lasting up at the 4th week. FO treatment (only at a dose of 3g/kg) significantly decreased the immobility frequency and increased the swimming frequency, but did not induce significant changes in the climbing frequency in DBT rats. Moreover, it was observed that DBT animals had significantly lower levels of BDNF in both hippocampus and pre frontal cortex when compared to NGL rats, which is completely prevented by FO treatment. In conclusion, our study demonstrates that FO treatment was able to prevent the mechanical allodynia and the depressive-like behaviors in DBT rats, which seems to be related to its capacity of BDNF level restoration. PMID- 26546882 TI - Age-dependent modulation of the somatosensory network upon eye closure. AB - Eye closure even in complete darkness can improve somatosensory perception by switching the brain to a uni-sensory processing mode. This causes an increased information flow between the thalamus and the somatosensory cortex while decreasing modulation by the visual cortex. Previous work suggests that these modulations are age-dependent and that the benefit in somatosensory performance due to eye closing diminishes with age. The cause of this age-dependency and to what extent somatosensory processing is involved remains unclear. Therefore, we intended to characterize the underlying age-dependent modifications in the interaction and connectivity of different sensory networks caused by eye closure. We performed functional MR-imaging with tactile stimulation of the right hand under the conditions of opened and closed eyes in healthy young and elderly participants. Conditional Granger causality analysis was performed to assess the somatosensory and visual networks, including the thalamus. Independent of age, eye closure improved the information transfer from the thalamus to and within the somatosensory cortex. However, beyond that, we found an age-dependent recruitment strategy. Whereas young participants were characterized by an optimized information flow within the relays of the somatosensory network, elderly participants revealed a stronger modulatory influence of the visual network upon the somatosensory cortex. Our results demonstrate that the modulation of the somatosensory and visual networks by eye closure diminishes with age and that the dominance of the visual system is more pronounced in the aging brain. PMID- 26546883 TI - A randomised trial comparing low-fat diets differing in carbohydrate and protein ratio, combined with regular moderate intensity exercise, on glycaemic control, cardiometabolic risk factors, food cravings, cognitive function and psychological wellbeing in adults with type 2 diabetes: Study protocol. AB - BACKGROUND: Hypocaloric low-fat diets, high in protein with moderate carbohydrate (HP) can enhance weight loss, improve glycaemic control and improve cardiometabolic health risk factors in type 2 diabetes mellitus (T2DM). However, it is unclear whether the metabolic benefits observed during weight loss are sustained during energy-balance and weight maintenance. Furthermore, there is a lack of evidence regarding the effect of HP diets on food cravings, cognitive function and psychological wellbeing in T2DM, despite carbohydrate food cravings, cognitive impairment and depression being associated with hyperglycaemia. METHODS/DESIGN: Overweight/obese adults with T2DM were randomised to consume either a HP diet (n=32, ~32% protein, 33% carbohydrate, 30% fat) or a higher carbohydrate diet (HC, n=29, ~22% protein, 51% carbohydrate, 22% fat) for 24 weeks with 30 min of moderate intensity exercise five days/week for the study duration. There were 2 phases: a 12 week weight loss phase followed by a 12 week weight maintenance phase. Primary outcome was glycaemic control (glycosylated haemoglobin; HbA1c). Secondary outcomes were cardiometabolic risk factors (body composition, fasting blood pressure, blood lipids, glucose, insulin and C reactive protein), food cravings, cognitive function (memory; psychomotor and executive function and psychological well-being. Outcomes were measured at baseline and the end of each 12-week intervention phase. Data will be analysed as intention-to-treat using linear mixed effects models. CONCLUSION: This study will examine the effects of two dietary interventions on health outcomes in T2DM during weight loss and notably following weight maintenance where there is a paucity of evidence. PMID- 26546884 TI - Anaerobic digestion of ultrasonicated sludge at different solids concentrations - Computation of mass-energy balance and greenhouse gas emissions. AB - Two cases of anaerobic digestion (AD) of sludge, namely (i) with pre-treatment and (ii) without pre-treatment, were assessed using mass-energy balance and the corresponding greenhouse gas (GHG) emissions. For a digestion period of 30 days, volatile solids degradation of the control sludge and the ultrasonicated secondary sludge was 51.4% and 60.1%, respectively. Mass balance revealed that the quantity of digestate required for dewatering, transport and land application was the lowest (20.2 * 10(6) g dry sludge/day) for ultrasonicated secondary sludge at 31.4 g TS/L. Furthermore, for ultrasonicated secondary sludge at 31.4 g TS/L, the maximum net energy (energy output - energy input) of total dry solids (TDS) was 7.89 * 10(-6) kWh/g and the energy ratio (output/input) was 1.0. GHG emissions were also reduced with an increase in the sludge solids concentration (i.e., 40.0 g TS/L < 30.0 g TS/L < 20.0 g TS/L). Ultrasonication pre-treatment proved to be efficient and beneficial for enhancing anaerobic digestion efficiency of the secondary sludge when compared to the primary and mixed sludge. PMID- 26546885 TI - Removal of arsenic from water using nano adsorbents and challenges: A review. AB - Many researchers have used nanoparticles as adsorbents to remove water pollutants including arsenic after modifying the properties of nanoparticles by improving reactivity, biocompatibility, stability, charge density, multi-functionalities, and dispersibility. For arsenic removal, nano adsorbents emerged as the potential alternatives to existing conventional technologies. The present study critically reviewed the past and current available information on the potential of nano adsorbents for arsenic removal from contaminated water and the challenges involved in that. The study discussed the separation and regeneration techniques of nano adsorbents and the performance thereof. The study evaluated the adsorption efficiency of the various nanoparticles based on size of nanoparticles, types of nano adsorbents, method of synthesis, separation and regeneration of the nano adsorbents. The study found that more studies are required on suitable holding materials for the nano adsorbents to improve the permeability and to make the technology applicable at the field condition. The study will help the readers to choose suitable nanomaterials and to take up further research required for arsenic removal using nano adsorbents. PMID- 26546886 TI - The positive correlation between upper adjacent vertebral fracture and the kyphosis angle of injured vertebral body after percutaneous kyphoplasty: An in vitro study. AB - OBJECTIVE: To investigate the correlation between the kyphosis angle of injured vertebral body and the risk of upper adjacent vertebral fracture after percutaneous kyphoplasty (PKP) using an osteoporotic vertebral compressed fracture model. MATERIALS AND METHODS: 24 functional spinal units (FSUs, T9 to L4) were selected from 6 elderly formalin preserved vertebral specimens to build the vertebral compressed fracture model. According to the kyphosis angle between the upper plate of upper vertebral body and the horizontal plane, group A (0 degrees ) and group B (20 degrees ) were defined, with each group comprised with 12 FSUs. The stiffness and fracture load were measured in both groups. RESULTS: After PKP, the stiffness was (571.513 +/- 83.373)N/mm and the fracture load was (1751.659 +/- 112.291)N in group A, with both significantly higher than those of group B (stiffness, (307.706 +/- 46.723)N/mm; fracture load, (1128.011 +/- 125.417)N). CONCLUSIONS: To reduce the risk of upper adjacent vertebral fracture, it is better to restore the height of injured vertebral body and decrease the angle of kyphosis to increase the capability of upper adjacent vertebral body against fracture. PMID- 26546887 TI - Lumbar juxta-facet joint cysts in association with facet joint orientation, tropism and -arthritis: A case-control study. AB - OBJECTIVE: To assess the association between juxta-facet-joint cysts (JFC) occurrence at the lumbar spine and Facet Joint (FJ) orientation, -tropism and arthritis. METHODS: Study group, 36 consecutive patients with JFC and the same number of controls, with degenerative diseases without JFC were match paired for demographics and spine segment. Parameter assessment was by T2-weighted axial MRI scans. JFC diagnosis was confirmed histopathologically. Group comparison was by Student's t-test for continuous variables and X(2) for categorical variables. RESULTS: Nineteen female and 17 male patients, aged between 45 and 85 years (mean 67.19 +/- 10.3 years) had a mean JFC size of 9.26 +/- 4.8mm occurring most frequently in the segment L4-L5 (75% n=25) and on the left side (61%). Mean FJ orientation of the study group was significantly more coronal compared to controls (left side 42 degrees vs 36 degrees , p<0.02*, 95% confidence interval: 0.9-11.5 and right side 43 degrees vs 37 degrees , p<0.02*, 95% confidence interval: 0.6-10.6 respectively). However, individual intersegmental analysis for study group patients showed the JFC bearing side to be significantly more sagittally oriented 40 degrees +/- 11.2 degrees compared to 45 degrees +/- 13.2 degrees for the side without FJC (p<0.03*, 95% confidence interval: 8.1 1.7). 50% of the study group showed FJ asymmetry compared to 30% in controls, with a trend for FJ tropism (p<0.07). Severe (grade 3) FJ arthritis was significantly more predominant in the study group 23/33 (p<0.001*) as compared to controls. CONCLUSIONS: Compared to a control group, JFC occurrence is associated with significant higher rates of arthritis and coronally orientated FJ. At intersegment comparison within the same patient cysts located in more sagittally orientated FJ and the asymmetric segments show a trend for FJ tropism. PMID- 26546888 TI - Human stem cell-based disease modeling: prospects and challenges. AB - Human stem cell-based disease models have great promise to advance our understanding of human disease. These models can be derived from patients with genetic disorders and manipulated with genome editing and myriad differentiation protocols to model pathologies in vitro. However, several challenges have impeded the full potential of stem cell-based in vitro disease modeling. Many genetically predisposed diseases take time to manifest and occur in specific tissue microenvironments, and these parameters are often not adequately modeled using conventional shorter-term monolayer cultures. These challenges must be overcome especially for cases where animal models also incompletely recapitulate the complex pathologies found in humans. As prominent ways to tackle these challenges we discuss here how advanced genome editing tools in human stem cells and human organoid cultures, specifically the example of intestinal organoids, contribute genetically defined models that recapitulate phenotypes of disease. PMID- 26546889 TI - Effect of grafted PEG chain conformation on albumin and lysozyme adsorption: A combined study using QCM-D and DPI. AB - In this study, elucidation of protein adsorption mechanism is performed using dual polarization interferometry (DPI) and quartz crystal microbalance with dissipation (QCM-D) to study adsorption behaviors of bovine serum albumin (BSA) and lysozyme (LYZ) on poly (ethylene glycol) (PEG) layers. From the analysis of DPI, PEG2000 and PEG5000 show tight and loose mushroom conformations, respectively. Small amount of LYZ could displace the interfacial water surrounding the tight mushroomed PEG2000 chains by hydrogen bond attraction, leading to protein adsorption. The loose mushroomed PEG5000 chains exhibit a more flexible conformation and high elastic repulsion energy that could prevent protein adsorption of all BSA and most of LYZ. From the analysis of QCM, PEG2000 and PEG5000 show tight and extended brush conformations. The LYZ adsorbed mass has critical regions of PEG2000 (0.19 chain/nm(2)) and PEG5000 (0.16 chain/nm(2)) graft density. When graft density of PEG is higher than the critical region (brush conformations), the attraction of hydrogen bonds between PEG and LYZ is the dominant factor. When graft density of PEG is lower than the critical region (mushroom conformations), elastic repulsion between PEG and proteins is driven by the high conformation entropy of PEG chains, which is the dominant force of steric repulsion in PEG-protein systems. Therefore, the adsorption of BSA is suppressed by the high elastic repulsion energy of PEG chains, whereas the adsorption of LYZ is balanced by the interactions between the repulsion of entropy elasticity and the attraction of hydrogen bonds. PMID- 26546890 TI - Phase behavior, microstructural transition, antimicrobial and antioxidant activities of a water-dilutable thymol microemulsion. AB - Pseudo ternary phase diagrams were constructed to assess the dilutability of thymol microemulsions using non-ionic (Tween 80), cationic (CTAB), and anionic (SDS) surfactants. We successfully constructed a thymol U-type microemulsion system using Tween 80 as surfactant and studied the microstructural transition along the dilution line at a 90/10 surfactant/oil mass ratio, with thymol and ethanol (3:1, w/w) as the oil phase. Differential scanning calorimetry analysis suggested that the microemulsions gradually inverted from the water-in-oil (W/O) (0-20% water) to the bicontinuous (25-35% water), and finally to the oil-in-water (O/W) (40-90% water) microstructures upon dilution, in good agreement with the conductivity measurements, while the rheological results indicated the collapse of rod-like micelles followed by formation of spherical micelles in the O/W region. The activities of the U-type thymol microemulsions are structural dependent. The antimicrobial activity against Escherichia coli and Staphylococcus aureus decreased when the microemulsions transformed from W/O to bicontinuous and O/W structures, while the DPPH scavenging activity increased. PMID- 26546891 TI - Human Leukocyte Antigens Influence the Antibody Response to Hepatitis B Vaccine. AB - Hepatitis B virus (HBV) infection and its sequelae such as cirrhosis and hepatocellular carcinoma has remained a serious public health problem throughout the world. The WHO strategy for effective control of HBV infection and its complications is mass vaccination of neonates and children within the framework of Expanded Programme on Immunization (EPI). Vaccination with hepatitis B surface antigen (HBsAg) induces protective antibody response (anti-HBs >= 10 IU/L) in 90 99% of vaccinees. The lack of response to HBsAg has been attributed to a variety of immunological mechanisms, including defect in antigen presentation, defect in HBsAg-specific T and/or B cell repertoires, T-cell suppression, increase in the regulatory T cell count, lack of necessary help of T-cells for production of anti HBs by B cells, defect in Th1 and/or Th2 cytokine production and selective killing of HBsAg-specific B-cells by human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes. The HLA complex plays an important role in many of these immunological processes. A variety of HLA class I, II, and III alleles and antigens have been reported to be associated with antibody response to HBsAg vaccination in different ethnic populations. Moreover, some HLA haplotypes were also associated with responsiveness to HBsAg. In this review the association of the HLA specificities with antibody response to hepatitis B (HB) vaccine is discussed. PMID- 26546892 TI - Th22 Cells Contribution in Immunopathogenesis of Rheumatic Diseases. AB - Newly identified T helper cell 22 (Th22) is a subset of CD4+T cells with specific properties apart from other known CD4+ T cell subsets with distinguished gene expression and function. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-alpha (TNF-alpha). The levels of Th22 and related cytokine IL-22 are increased in various autoimmune diseases and positively associated with some rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, behcet's disease, ankylosing spondylitis and psoriatic arthritis. In summary, IL 22 and Th22 cells play a significant and complicated role in inflammatory and autoimmune rheumatic diseases, therefore, targeting IL-22 or Th22 have unique and attractive advantages due to the fact that Th22 subset is recently identified and its associated research is extremely limited. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of rheumatic disease. PMID- 26546893 TI - Association between Peptidylarginine Deiminase Type 4 rs1748033 Polymorphism and Susceptibility to Rheumatoid Arthritis in Zahedan, Southeast Iran. AB - There are controversial reports regarding the role of peptidylarginine deiminase type 4 (PADI4) gene polymorphisms and risk of Rheumatoid arthritis (RA). The aim of the present study was to investigate the impact of PADI4 rs1748033 polymorphism and susceptibility to RA in a sample of the Iranian population. This case-control study was done on 150 patients with RA and 150 healthy subjects.PADI4 rs1748033 genotyping was done using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) assay. The PADI4 rs1748033 variant increased the risk of RA in codominant (OR=1.67, 95%CI=1.03-2.71, p=0.048, CT vs CC; OR=2.73, 95%CI=1.25-5.97, p=0.013, TT vs CC) and dominant (OR=1.84, 95%CI=1.15-2.92, p=0.014, CT+TT vs CC) tested inheritance models. In addition, the PADI4 rs1748033 T allele increased the risk of RA (OR=1.63, 95%CI=1.16-2.29, p=0.006) in comparison with C allele. In conclusion, our finding indicated that PADI4 rs1748033 gene polymorphism increased the risk of RA in a sample of the Iranian population. PMID- 26546894 TI - Molecular Diversity of Macrophages in Allergic Reaction: Comparison between the Allergenic Modes; Th1- and -Th2-Derived Immune Conditions. AB - Activated macrophages have been classified into classical (M1) and alternative (M2) macrophages. We aimed to establish a method to yield enough number of macrophages to analyze their molecular, biological and immunological functions. We used drugs; adjuvant albumin from chicken egg whites--Imject Alum (OVA-Alum) and OVA Complete Freund Adjuvant (OVA-CFA), to induce macrophages to M2 and M1 respectively. We analyzed the phenotype of purified macrophages induced under these immune conditions, using flow cytometry (FACS) to detect cell-surface molecules and the enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines. The cDNA microarray was employed to measure changes in expression level of cell surface protein between M1 and M2 macrophages. Phenotype analysis of purified macrophages, induced under these immune conditions, showed macrophages induced by OVA-Alum was almost M2 while the proportion of M1 macrophages induced by OVA-CFA was significantly higher. The results also showed higher expression level of macrophage galactose N- acetyl-galactosamine specific lectin-2 protein (MGL1/2-PE), a known M2 macrophage marker, on the surface of Alum-induced macrophages. On the basis of these preliminary data, ELISA results revealed that after macrophage stimulation with lipopolysaccharides (LPS), the level of interleukin (IL)-10 produced by Alum- induced macrophages was higher than the level of IL-10 produced by CFA-induced macrophages. In contrast, the level of tumor necrosis factor-alpha (TNF-alpha) produced by CFA-induced macrophages was higher than Alum-induced macrophages. The cDNA microarray confirmed previous results and suggest immunoglobulin-like type 2 receptor alpha (Pilra) as a new marker for M1, macrophage galactose N-acetylgalactosamine specific lectin 2 (Mgl2) as M2 macrophages marker. PMID- 26546895 TI - Imbalance of Peripheral Th17 and Regulatory T Cells in Children with Allergic Rhinitis and Bronchial Asthma. AB - The purpose of the present study is to investigate the prevalence of Th17 and regulatory T (Treg) cells in children with allergic rhinitis (AR) accompanying with bronchial asthma (BA). 24 children with AR, 22 children with BA, 18 children with AR accompanying with BA, and 20 healthy controls were recruited. The prevalence of peripheral blood Th17 and Treg cells were determined by flow cytometry. mRNA expression of retinoid-acid receptor-related orphan receptor (ROR)-gammat and forkhead box P3 (Foxp3) were determined by realtime polymerase chain reaction. Cytokine expressions in plasma were determined by enzyme linked immunosorbent assay. The frequency of Th17 cells, ROR-gammat mRNA expression, and the plasma levels of IL-17 were significantly higher, while Treg cells and Transforming growth factor (TGF)-beta1 were significantly lower in children with AR accompanying with BA compared with those in children with AR or BA alone or control subjects. In children with allergic airway disease, total IgE levels were positively correlated to the frequency of Th17 cells (r=0.607, p<0.01), plasma IL 17 levels, and negatively correlated to the frequency of Treg cells (r=-0.429, p<0.01) and TGF-beta1 levels (r=-0.224, p<0.01). While Forced expiratory volume in one second (FEV1) (% predicted) was negatively correlated to the frequency of Th17 cells (r=-0.602, p<0.01), plasma IL-17 levels (r=-0.577, p<0.01), and positively correlated to the frequency of Treg cells r=0.504, p<0.01) and TGF beta1 levels (r=0.231, p<0.05). Our results demonstrate that the imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR accompanying with BA. PMID- 26546896 TI - Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis. AB - Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients. PMID- 26546897 TI - Association of Tumor Necrosis Factor Alpha 308 G/A Polymorphism with Asthma in Pakistani Population. AB - Asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. The role of tumor necrosis factor-alpha (TNF-alpha) in asthma is unclear in Pakistani population. The aim of this study was to assess the relationship between TNF alpha-308 polymorphism and asthma. Polymorphism of TNF-alpha (G-308-A locus; rs 1800629) in 329 asthmatic patients and 151 healthy controls was evaluated. DNA was prepared from blood samples of cases and controls. Samples were genotyped for TNF-alpha 308 G/A polymorphism. There was no significant difference in the frequency of GG (OR 1.049 with 95% CI 0.68-1.63) and GA (OR 0.987 with 95% CI 0.64-1.53) genotypes of TNF-alpha-308. The AA genotype was absent in cases and only one AA genotype was observed in the controls. The genetic polymorphism of TNF-alpha does not seem to be associated with asthma in Pakistani population. PMID- 26546898 TI - Plasma Adiponectin Concentrations and Adiponectin Gene Polymorphisms Are Associated with Bronchial Asthma in the Chinese Li Population. AB - The purpose of this study was to determine the clinical significance of changes in the plasma adiponectin concentration in patients with bronchial asthma and to test the association between the single nucleotide polymorphisms (SNPs) rs2241766 and rs1501299 in the ADIPOQ gene and bronchial asthma in the Chinese Li population. We selected 120 cases and 120 controls, and plasma adiponectin, interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme-linked immunosorbent assay (ELISA). In addition, we genotyped two tag single nucleotide polymorphisms (tSNPs) and evaluated their association with bronchial asthma using the chi2 test and genetic model analysis. Compared to controls, patients with acute exacerbation of bronchial asthma showed significantly lower adiponectin and significantly higher IL-6 and TNF-alpha levels (p<0.01). A positive association was found between the rs1501299 SNP and acute exacerbation (OR=1.62; 95% CI=1.08-2.43; p=0.019). The inverse correlation between the plasma adiponectin concentration and asthma exacerbation indicates that adiponectin may play a protective role in the pathogenesis of asthma. Meanwhile, our findings suggest that ADIPOQ polymorphisms influence the risk of developing bronchial asthma in Chinese Li population. PMID- 26546899 TI - Evaluation of Soluble Human Leukocyte Antigen-G (sHLA-G) Isoforms and Regulatory T Cells in Relapsing-Remitting Multiple Sclerosis. AB - Soluble forms of nonclassical human leukocyte antigen (HLA)-G have recently been suggested as immunomodulatory factors in multiple sclerosis (MS). HLA-G inhibits the effecter function of T cells and natural killer (NK) cells. Also regulatory T cells (Treg) are considered as pivotal players in MS pathogenesis. Thus, we aimed to evaluate the presence of HLA-G molecules and Treg cells in Relapsing-Remitting Multiple Sclerosis (RRMS) patients and compare it to healthy controls. Patients with RRMS (n=205, mean age=31.32+/-8.53) and healthy subjects (n=205, mean age=32.2+/-7.48) were studied. The patients subgrouped to untreated and treated with Interferon beta. Then sHLA-G levels (sHLA-G1 and sHLA-G5) were measured using ELISA method. Treg (CD4+ CD25+ Foxp3+) cells in patients who had sHLA-G>10 U/ml were characterized by using flow cytometry. Our data showed that there was no significant differences between RRMS patients and healthy controls in sHLA-G concentration (p>0.05). Treg cell frequencies were higher in the patients who had sHLA-G >10 U/ml compared to healthy subjects (p<0.05). Collectively, there was significant correlation between sHLA-G and frequency of Treg cells in treated RRMS patients and healthy individuals. It seems that high level sHLA-G has been instrumental in raising frequency of Treg cells in treated patients and could be associated with remission of MS disease. PMID- 26546900 TI - Association of HLA-DRB1 Alleles with Ulcerative Colitis in the City of Kerman, South Eastern Iran. AB - The association of HLA class II genes with ulcerative colitis (UC) as an autoimmune disease has been investigated for several years. However, factors responsible for genetic predisposition of this disease have so far not been clearly understood. In this study, for the first time, we aimed to investigate the association between HLA-DRB1 types and UC in the population of Kerman, a city southeast Iran. HLA typing was performed among 85 UC patients and 95 healthy controls using PCR amplification, employing sequence specific primers (PCR-SSP). The DRB1 frequencies were determined in the patients and controls. HLA-DRB1*04 was negatively associated with UC. Furthermore, HLA-DRB1*13 was significantly associated with severity of the disease (p=0.01) among UC patients. This is the novel result that describes an association of HLA-DRB1*13 with UC and also shows the protective role of HLA-DRB1*04 against the disease in people of Kerman. PMID- 26546901 TI - The Opposite Effects of DNA and Protein Components of Listeria Monocytogenes and Toxoplasma gondii on Immunologic Characteristics of Dendritic Cells. AB - The innate immune system utilizes pattern recognition receptors (PRRs) to recognize microbes. Pathogens contain various molecules with diverse effects on immune response. In this study, we evaluated the effect of DNA and protein components derived from two intracellular microorganisms including Listeria monocytogenes (L. monocytogenes) and Toxoplasma gondii (T. gondii) on dendritic cells (DCs) activation and ensuing adaptive immune responses. DNA and protein components of L. monocytogenes and T. gondii were prepared using relevant kits. DNA and protein components of these two pathogens were added to immature DCs (iDCs). Subsequently, co-stimulatory expression and cytokine production by DCs were measured. Finally, we evaluated the stimulatory capacity of mature DCs (mDCs) in DC-T cells co-culture. The results showed that protein matured-DCs produced higher level of IL (Interleukin)-12p70. There was also a significant increase in Interferon-Gamma (IFN-gamma) production and proliferative capacity in T cells co-cultured with protein matured-DCs. On the other hand, DNA matured-DCs produced significantly higher amounts of Transforming growth factor-beta (TGF beta). Collectively, these results imply a regulatory nature for DNA and potent stimulatory character for protein components of these two intracellular microorganisms. PMID- 26546902 TI - Transforming Growth Factor Beta-Induced Is Essential for Endotoxin Tolerance Induced by a Low Dose of Lipopolysaccharide in Human Peripheral Blood Mononuclear Cells. AB - Our prior study found that transforming growth factor beta-induced (TGFBI) is an important negative regulator in TLR-induced inflammation. However, whether TGFBI may affect inflammation during lipopolysaccharide (LPS)-induced endotoxin tolerance (ET) is still unclear. This study aimed to investigate whether TGFBI was involved in the mechanisms of ET in human through dampening nuclear factor kappa B (NF-kappaB) mediated pathway. ET models of isolated healthy volunteers peripheral blood mononuclear cells (PBMCs) were established by pretreating with a low dose of LPS to observe the changes of TGFBI expression during ET induction, compared with ten healthy controls. Moreover, a vector-based short hairpin RNA expression system was used to specifically inhibit TGFBI expression to further explore its role in ET induction. The expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The responses to LPS were determined by the activation of NF-kappaB, the production of tumor necrosis factor-alpha (TNF-alpha) and Nitric Oxide (NO), which were analysed by enzyme-linked immuno sorbent assay (ELISA). The results showed that TGFBI expression in the ET group obviously increased; ET also led to a hyporesponse of PBMCs to LPS with less activation of NF-kappaB, less production of TNF-alpha and NO, as well as more expression of TGFBI than those of non-ET group. Moreover, the inhibitory effect was partly refracted in plasmid TGFBI short hairpin RNA (pTGFBI-shRNA) transfected PBMCs. Meanwhile, the absence of TGFBI caused abnormal enhancement of inflammatory cytokine production and it was involved in ET induction through dampening NF-kappaB mediated pathway. Therefore, TGFBI may be a new target for the clinical treatment of inflammatory disorders. PMID- 26546903 TI - Clericuzio-type Poikiloderma with Neutropenia Syndrome in a Turkish Family: a Three Report of Siblings with Mutation in the C16orf57 gene. AB - Clericuzio-type poikiloderma with neutropenia (PN) is characterized by poikiloderma, non-cyclic neutropenia, recurrent sinopulmonary infections, pachyonychia, and palmo-plantar hyperkeratosis. Mutations in the C16orf57 gene, which is located on chromosome 16q13, have been identified as the cause of PN. PN was first described by Clericuzio in Navajo Indians. Herein, we reported the clinical presentations and laboratory investigations of PN in three siblings from Turkey. The older siblings presented with typical cutaneous poikiloderma, plantar keratoderma, pachyonychia of toenails, and recurrent upper respiratory infections. As the most affected patient, in addition to classic manifestations, the youngest sibling had recurrent pneumonia, hepatosplenomegaly, dental caries, failure to thrive, and hand malformation. Genetic study revealed a homozygous mutation (c.531delA) in the C16orf57 gene in siblings. With the presented study, we aimed to draw attention to PN which can be a predisposing factor to malignancies. PMID- 26546904 TI - Familial Churg-Strauss Syndrome in a Sister and Brother. AB - Churg-Strauss syndrome (CSS) is a granulomatous small vessel vasculitis. It is characterized by asthma, allergic granulomatosis and vasculitis. This syndrome is rare in children. A 5 years old boy was admitted with cough, fever and dyspnea for 2 weeks. On the basis of laboratory data (peripheral eosinophilia), associated with skin biopsy, and history of CSS in his sister, this disease was eventually diagnosed. The patient had good response to corticosteroid. In every asthmatic patient with prolonged fever, eosinophilia and multisystemic involvment, CSS should be considered. PMID- 26546905 TI - Ideal Diagnostic Tool and Proper Statistical Analysis Improve the Credibility of the Study. PMID- 26546906 TI - Evaluation of silkworm excrement and mushroom dreg for the remediation of multiple heavy metal/metalloid contaminated soil using pakchoi. AB - The economical, environmental friendly and efficient materials to remediate the pollution with multiple heavy metals and metalloids are scarce. Silkworm excrement (SE) and mushroom dregs (MD) are two types of agricultural wastes, and they are widely used to improve the soil fertility in many regions of China. A pot experiment with sixteen treatments was set up to assess the possibility of using SE and MD to stabilize heavy metals and metalloids and reduce their uptake in pakchoi cultivated in slightly contaminated soils with arsenic (As), cadmium (Cd), lead (Pb) and zinc (Zn). The results showed that the single addition of SE obviously stimulated the growth of pakchoi, reduced the contents of all tested heavy metals and metalloids in the edible part of pakchoi and availability of Zn and Cd in soil. The single MD treatment showed an inferior ability to enhance the growth and reduce the contents of heavy metals and metalloids in the edible part of pakchoi. The combined utilization of SE and MD appeared not to show better effects than their individual treatment when using them to remediate this contaminated soil. Some potential mechanisms on the stimulation on pakchoi growth and decreasing the accumulation of heavy metals and metalloids in pakchoi subjected to SE were suggested, including: (1) enhancing soil pH to impact the availability of heavy metals and metalloids; (2) improve the fertility of soil; (3) sulfhydryl groups of organic materials in SE play a role in conjugating heavy metals and metalloids to affect their availability in soil; and (4) stimulating the growth of pakchoi so as to show a "dilution effect" of heavy metals and metalloids. PMID- 26546907 TI - Proteomic analysis of chromium stress and sulfur deficiency responses in leaves of two canola (Brassica napus L.) cultivars differing in Cr(VI) tolerance. AB - Sulfur (S) is an essential macronutrient for plant growth and development, and it plays an essential role in response to environmental stresses. Plants suffer with combined stress of S deficiency and hexavalent chromium [Cr(VI)] in the rhizosphere. Little is known about the impact of S deficiency on leaf metabolism of canola (Brassica napus L.) under Cr(VI) stress. Therefore, this study is the first to examine the effects of Cr(VI) stress and S deficiency in canola at a molecular level. A comparative proteomic approach was used to investigate the differences in protein abundance between Cr-tolerant NK Petrol and Cr-sensitive Sary cultivars. The germinated seeds were grown hydroponically in S-sufficient (+S) nutrient solution for 7 days and then subjected to S-deficiency (-S) for 7 days. S-deficient and +S seedlings were then exposed to 100MUM Cr(VI) for 3 days. Protein patterns analyzed by two-dimensional electrophoresis (2-DE) revealed that 58 protein spots were differentially regulated by Cr(VI) stress (+S/+Cr), S deficiency (-S/-Cr) and combined stress (-S/+Cr). Of these, 39 protein spots were identified by MALDI-TOF/TOF mass spectrometry. Differentially regulated proteins predominantly had functions not only in photosynthesis, but also in energy metabolism, stress defense, protein folding and stabilization, signal transduction, redox regulation and sulfur metabolism. Six stress defense related proteins including 2-Cys peroxiredoxin BAS1, glutathione S-transferase, ferritin 1, l-ascorbate peroxidase, thiazole biosynthetic enzyme and myrosinase-binding protein-like At3g16470 exhibited a greater increase in NK Petrol. The stress related proteins play an important role in the detoxification of Cr(VI) and maintaining cellular homeostasis under variable S nutrition. PMID- 26546908 TI - Silver nanoparticles disrupt regulation of steroidogenesis in fish ovarian cells. AB - Despite the influx of silver nanoparticles (nAg) into the marine environment, their effects on fish reproduction remain completely unexplored. Using ovarian primary cells from marine medaka (Oryzias melastigma), in vitro studies were carried out to evaluate the effects of two differently coated nAg particles (Oleic Acid, (OA) nAg and Polyvinylpyrrolidone, (PVP) nAg) on fish ovarian tissues, using AgNO3 as a positive control. Cytotoxicity was evaluated by MTT assay and expression of key genes regulating steroidogenesis (StAR, CYP 19a, CYP 11a, 3betaHSD and 20betaHSD) were determined by Q-RT-PCR. EC50 values for PVP nAg, OA nAg and AgNO3 were 7.25MUgL(-1), 924.4MUgL(-1), and 42.0MUgL(-1) respectively, showing that toxicity of silver was greatly enhanced in the PVP coated nano-form. Down regulation of CYP 19a was observed in both nAg and AgNO3 treatments, while down regulation of 3betaHSD was only found in the OA nAg and AgNO3 treatments. For the first time, our results demonstrated that nAg can affect specific genes regulating steroidogenesis, implicating nAg as a potential endocrine disruptor. PMID- 26546909 TI - Vitroceramic interface deposited on titanium substrate by pulsed laser deposition method. AB - Pulsed laser deposition (PLD) method was used to obtain biovitroceramic thin film coatings on titanium substrates. The composition of the targets was selected from SiO2-CaO-P2O5-(CaF2) systems and the corresponding masses were prepared using the sol-gel method. The depositions were performed in oxygen atmosphere (100mTorr), while the substrates were heated at 400 degrees C. The PLD deposited films were analysed through different experimental techniques: X-ray diffraction, scanning (SEM, EDX) and transmission (HRTEM, SAED) electron microscopy and infra-red spectroscopy coupled with optical microscopy. They were also biologically tested by in vitro cell culture and the contact angle was determined. The bioevaluation results indicate a high biocompatibilty of the obtained materials, demonstrating their potential use for biomedical applications. PMID- 26546910 TI - Effect of the surface free energy of materials on the lamination tendency of bilayer tablets. AB - Dosage forms with fixed dose combinations of drugs is a frequent and advantageous mode of administration, but their production involves a number of technological problems. Numerous interactions in a homogeneous vehicle may be avoided through the use of layered tablets. The mechanical properties of these dosage forms depend on numerous process parameters and material characteristics. The aim of the present study was a detailed investigation of the relationships between the surface characteristics and deformation properties of tableting materials and the tendency of bilayer tablets to undergo lamination. Bilayer tablets were compressed from unlubricated materials with different plastic-elastic properties and surface free energies according to a mixed 2 and 3-level half-replicated factorial design. The results revealed that the surface characteristics play the main role in the lamination of layered tablets and the effect of the plastic elastic behavior cannot be interpreted without a knowledge of these properties. PMID- 26546911 TI - How mathematical modeling tools are helping the pharmaceutical sciences. PMID- 26546912 TI - Identification of potential virulence factors of Cronobacter sakazakii isolates by comparative proteomic analysis. AB - Cronobacter is a group of important foodborne pathogens associated with neonatal meningitis, septicemia, and necrotizing enterocolitis. Among Cronobacter species, Cronobacter sakazakii is the most common species in terms of isolation frequency. However, the molecular basis involved in virulence differences among C. sakazakii isolates is still unknown. In this study, based on the determination of virulence differences of C. sakazakii G362 (virulent isolate) and L3101 (attenuated isolate) through intraperitoneal injection, histopathologic analysis (small intestine, kidney, and liver) further confirmed virulence differences. Thereafter, the potential virulence factors were determined using two-dimensional electrophoresis (2-DE) coupled with MALDI/TOP/TOF mass spectrometry. Among a total of 36 protein spots showing differential expression (fold change>1.2), we identified 31 different proteins, of which the expression abundance of 22 was increased in G362. These up-regulated proteins in G362 mainly contained DNA starvation/stationary phase protection protein Dps, OmpA, LuxS, ATP-dependent Clp protease ClpC, and ABC transporter substrate-binding proteins, which might be involved in virulence of C. sakazakii. This is the first report to determine the potential virulence factors of C. sakazakii isolates at the proteomic levels. PMID- 26546913 TI - Evaluation of carcass traits and meat characteristics of Guzerat-crossbred bulls. AB - Our objective was to evaluate carcass and meat characteristics of Guzerat crossbred bulls finished in feedlot. Carcasses from 18 bulls, randomly selected from a larger group of 36 bulls, consisting of F1 Guzerat*Holstein ("Guzholstein"); F1 Guzerat*Nellore ("Guzonell"); and 1/2 Simmental+1/4 Guzerat+1/4 Nellore (Three-Cross; n=6 each group) were used. Cold carcass weight was greater (P=0.01) for Three-Cross compared with "Guzonell" and "Guzholstein". Three-Cross carcasses had greater (P<0.01) rib-eye-area and 100-kg-adjusted rib eye-area among groups. Longissimus lumborum length did not differ (P>0.05) among groups, but depth was greater (P<0.01) for Three-Cross compared with other groups. "Guzholtein" had lesser (P=0.05) shear force compared with "Guzonell", with Three-Cross being intermediate. We conclude that "Guzholstein" is an adequate option for producers willing to finish this kind of genetic group, as it is comparable or better than Bos indicus crosses and B. indicus*Bos taurus bulls. PMID- 26546914 TI - PEGylated NaHoF4 nanoparticles as contrast agents for both X-ray computed tomography and ultra-high field magnetic resonance imaging. AB - It is well-known that multimodal imaging can integrate the advantages of different imaging modalities by overcoming their individual limitations. As ultra high field magnetic resonance imaging (MRI) will be inevitably used in future MRI/X-ray computed tomography (CT) scanner, it is highly expected to develop high performance nano-contrast agents for ultra-high field MR and CT dual-modality imaging, which has not been reported yet. Moreover, specific behavior of nano contrast agents for ultra-high field MRI is a challenging work and still remains unknown. Herein, a novel type of NaHoF4 nanoparticles (NPs) with varied particle sizes were synthesized and explored as high-performance dual-modality contrast agents for ultra-high field MR and CT imaging. The specific X-ray absorption and MR relaxivity enhancements with varied nanoparticle diameters (3 nm, 7 nm, 13 nm and 29 nm) under different magnetic field (1.5/3.0/7.0 T) are investigated. Based on experimental results and theoretical analysis, the Curie and dipolar relaxation mechanisms of NaHoF4 NPs are firstly separated. Our results will greatly promote the future medical translational development of the NaHoF4 nano contrast agents for ultra-high field MR/CT dual-modality imaging applications. PMID- 26546915 TI - Neoangiogenesis of human mesenchymal stem cells transfected with peptide-loaded and gene-coated PLGA nanoparticles. AB - Several factors are involved in angiogenesis. To form new blood vessels, we fabricated vehicles carrying an angiogenesis-related peptide (apelin) and gene (vascular endothelial growth factor (VEGF)165) that were internalized by human mesenchymal stem cells (hMSCs). These non-toxic poly-(DL)-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) easily entered hMSCs without cytotoxicity. The negatively charged outer surface of PLGA NPs can be easily complexed with highly positively charged polyethylenimine (PEI) to deliver genes into cells. PLGA NPs complexed with PEI could be coated with negatively charged VEGF plasmid DNA and loaded with apelin. The physical characteristics of these PLGA NPs were determined by size distribution, gel retardation, and morphological analyses. Transfection of VEGF-coated apelin-loaded PLGA NPs resulted in the differentiation of hMSCs into endothelial cells and vascular formation in Matrigel in vitro. Following injection of hMSCs transfected with these PLGA NPs into an ischemic hind limb mouse model, these cells differentiated into endothelial cells and accelerated neovascularization. PMID- 26546916 TI - Smart and hyper-fast responsive polyprodrug nanoplatform for targeted cancer therapy. AB - The rapid development and clinical trials of biodegradable nanoparticles (NPs) are heavily hindered by many factors, including poor drug loading, low drug concentration at disease sites, lack of active targeting function, etc. Herein, we developed a new smart and hype-responsive polyprodrug platform with five key elements (i.e. chemically incorporated drug molecules in backbone, stimuli responsive bond, hyper-fast chain-breakage ability, hydrophilic segment and targeting ligand). Using 10-hydroxycamptothecin (HCPT) as model drug, we designed and prepared an exemplified redox-responsive amphiphilic polyprodrug via polycondensation and "click" chemistry. This polymer is composed of a hydrophobic HCPT-based polyprodrug, a hydrophilic poly(ethylene oxide) (PEG) chain and a tumor-targeting RGD tail. Employing nanoprecipitation technique, small-sized NPs (<70 nm) can be obtained. The in vitro and in vivo results prove that this newly developed nanoplatform has the following unique characteristics: 1) high and constant drug loading (>36 wt.%), 2) excellent tumor-targeting performance, 3) hyper-fast redox-responsive drug release (around 70% accumulative release within 2 h), 4) long blood circulation and 5) significant inhibition of tumor growth without side effects. PMID- 26546917 TI - Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone. AB - Biocompatibility is a key issue in the development of new implant materials. In this context, a novel class of biodegrading Mg implants exhibits promising properties with regard to inflammatory response and mechanical properties. The interaction between Mg degradation products and the nanoscale structure and mineralization of bone, however, is not yet sufficiently understood. Investigations by synchrotron microbeam x-ray fluorescence (MUXRF), small angle x ray scattering (MUSAXS) and x-ray diffraction (MUXRD) have shown the impact of degradation speed on the sites of Mg accumulation in the bone, which are around blood vessels, lacunae and the bone marrow. Only at the highest degradation rates was Mg found at the implant-bone interface. The Mg inclusion into the bone matrix appeared to be non-permanent as the Mg-level decreased after completed implant degradation. MUSAXS and MUXRD showed that Mg influences the hydroxyl apatite (HAP) crystallite structure, because markedly shorter and thinner HAP crystallites were found in zones of high Mg concentration. These zones also exhibited a contraction of the HAP lattice and lower crystalline order. PMID- 26546918 TI - Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells. AB - Bioactive scaffolds for tissue engineering call for demands on new materials which can enhance traditional biocompatibility requirements previously considered for clinical implantation. The current commercially available thermoplastic materials, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(epsilon-caprolactone) (PCL) and their copolymers, have been used to fabricate scaffolds for regenerative medicine. However, these polymers have limitations including lacking of broadly tuning mechanical and degradable properties, and activation of specific cell-scaffold interactions, which limit their further application in tissue engineering. In the present study, electrospun scaffolds were successfully fabricated from a new class of block poly(butylene succinate)-based (PBS-based) copolyesters containing either butylene thiodiglycolate (BTDG) or butylene diglycolate (BDG) sequences. The polyesters displayed tunable mechanical properties and hydrolysis rate depending on the molecular architecture and on the kind of heteroatom introduced along the polymer backbone. To investigate their potential for skeletal regeneration, human mesenchymal stromal cells (hMSCs) were cultured on the scaffolds in basic, osteogenic and chondrogenic media. Our results demonstrated that PBS-based copolyesters containing thio-ether linkages (i.e. BTDG segments) were more favorable for chondrogenesis of hMSCs than those containing ether linkages (i.e. BDG sequences). In contrast, PBS-based copolyesters containing ether linkages showed enhanced mineralization. Therefore, these new functional scaffolds might hold potential for osteochondral tissue engineering applications. PMID- 26546919 TI - Genomic structure and promoter characterization of the CDPK kinase gene expressed during seed formation in Pharbitis nil. AB - CDPK kinases are a unique class of calcium sensor/responders that regulate many growth and developmental processes as well as stress responses of plants. PnCDPK1 kinase from Pharbitis nil is regulated by light and contributes to seed germination, seedling growth and flower formation. Following an earlier work in which we identified the PnCDPK1 coding sequence and a 330bp long 3'UTR (untranslated region), we present for the first time the genomic organization of PnCDPK1, including intron analysis and the gene copy number designation. We completed the research by identifying the 5'-flanking region of PnCDPK1 and analyzed it in silico, which led to the discovery of several cis-regulatory elements involved in light regulation, embryogenesis and seed development. The functional analysis of P. nil CDPK showed characterization of the PnCDPK1 transcript and PnCDPK protein level during seed formation and fruit maturation. The greatest amount of PnCDPK1 mRNA was present in the last stages of seed maturation. Moreover, two PnCDPK proteins of different molecular masses were discovered during fruit development, showing various protein accumulation and activity profile. The 56kDa protein dominated in the early stages of fruit development, whereas the smaller protein (52kDa) was prominent in the latter stages. PMID- 26546920 TI - Formulation and stabilization of riboflavin in liposomal preparations. AB - A study of the formulation of liposomal preparations of riboflavin (RF) with compositional variations in the content of phosphatidylcholine (PC) and their entrapment efficiency (26-42%) have been conducted. Light transmission characteristics of the liposomal preparations have been determined to evaluate their effect on the amount of light passing through the system to initiate a photochemical reaction. Dynamic light scattering (DLS) and atomic force microscopy (AFM) have been used to study the physical characteristics of liposomes. The liposomal preparations of RF have been subjected to photolysis using visible light and the apparent first- order rate constant, kobs, for the degradation of RF have been determined. The values of kobs (1.73-2.29*10(-3)min( 1)) have been found to decrease linearly with an increase in PC concentration in the range of 12.15 to 14.85 mM. Thus, an increase in PC concentration of liposomes leads to an increase in the stability of RF. RF and its main photoproduct, lumichrome (LC), formed in liposomes have been assayed by a two component spectrometric method at 356 and 445 nm using an irrelevant absorption correction to compensate for the interference of liposomal components. The fluorescence measurements of RF in liposomes indicate excited singlet state quenching and the formation of a charge-transfer complex between RF and PC. It results in electron transfer from PC to RF to cause photoreduction and stabilization of RF. PMID- 26546921 TI - Application of ceramic membranes for microalgal biomass accumulation and recovery of the permeate to be reused in algae cultivation. AB - The present study was carried out to investigate the possibility of using ceramic membranes for microalgal biomass densification and to evaluate the qualitative composition of the permeate as a source of nitrogen and phosphorus for microalgae cultivated in a closed system. The studies were conducted on the microalga Monoraphidium contortum. The microfiltration process was carried out on a quarter technical scale using ceramic membranes with 1.4 MUm, 300 and 150 kDa cut-offs. Permeate flux and respective hydraulic resistances were calculated. Dissolved inorganic nitrogen and phosphorus fractions were measured in the feed and the permeate. It was noted that the permeate flux in the MF process was decreasing while the values of reversible and irreversible resistances were increasing as the cut-off of the studied membranes was diminishing. An analysis of the hydraulic series resistance showed that using a 300 kDa membrane would be the most beneficial, as it was characterized by a comparatively high permeate flux (Jv=1.68 10(-2)m(3)/m(2)s), a comparatively low susceptibility to irreversible fouling (1.72.10(9) 1/m) and a high biomass retention coefficient (91%). The obtained permeate was characterized by high concentrations of dissolved nitrogen and phosphorus forms, which indicated that it could be reused in the process of microalgal biomass production. PMID- 26546922 TI - [Exceptional view of a new website...]. PMID- 26546923 TI - [About the technique of muscle biopsy - A historical flash-back on the technique of muscle biopsie]. PMID- 26546924 TI - [Chanarin-Dorfman syndrome in a 7-year-old child: when myophathy and skin involvement are all but one]. PMID- 26546925 TI - [Are respiratory muscle testing helpful to prompt sleep studies in children with neuromuscular disease?]. PMID- 26546926 TI - [DM-SCOPE, an intermediary appraisal report and benefits of databases in neuromuscular disorders]. PMID- 26546927 TI - [GNE myopathy]. AB - GNE myopathy is a rare neuromuscular disease whose description is fairly recent. It predominantly affects the adult population and is an inherited autosomal recessive disorder. Although universal and ubiquitous, GNE myopathy prevails in the Jewish community of Persian origin, living in Iran, Israel or in the United States. This condition has also been reported in great number in populations of far-East Asia (Japan and neighboring countries) and, closer to France, in Bulgaria. GNE myopathy causes muscle weakness in the extremities (distal myopathy), affecting initially and predominantly foot flexor muscles. The generic term of GNE myopathy is now fully accepted and encompasses two previously described entities: the quadriceps sparing myopathy, (also referred to as the autosomal recessive form of inclusion body myopathy (hIBM) and the Nonaka type distal myopathy (or distal myopathy with rimmed vacuoles DMRV). This myopathy is due to mutations in the GNE gene encoding a bifunctional enzyme, the UDP-N acetylglucosamine-2-epimerase/N-acetylmannosamine kinase. This enzyme plays a role at two levels in the metabolic pathway leading to the synthesis of sialic acid. Sialic acid, also known as N-acetylneuraminic acid (Neu5Ac or NANA), is a monosaccharide essential to other protein or lipid molecules requiring sugar residues on their surface in order to function efficiently. GNE myopathy is characterized by histological lesions (rimmed vacuoles) within muscle fibers. They are fairly typical in a suggestive context, but non-specific and inconsistent from one muscle to another. The diagnosis of GNE myopathy is essentially based on clinical clues, including muscle imaging, and is confirmed by genetic studies. If promising therapeutic trials are being developed to compensate for this recently unveiled metabolic defect, the treatment of this myopathy remains purely supportive to date. PMID- 26546928 TI - [Not Available]. PMID- 26546929 TI - [Not Available]. PMID- 26546930 TI - [Not Available]. PMID- 26546931 TI - [Myology and ethnic minorities: all roads lead to the Roma]. PMID- 26546932 TI - [First Italo-French meeting on laminopathies and other pathologies related to the nuclear envelope]. PMID- 26546933 TI - [The Emeritus Dinosaur's viewpoint - The road to hell of gene therapists is paved with POC]. PMID- 26546936 TI - [The French Myology Association Telethon--investments in innovative projects]. PMID- 26546937 TI - [Patient safety: prescription of drugs that prolong the QT interval]. AB - OBJECTIVE: to determine the prescription of drugs with known risk to prolong the QT interval in a Healthcare Area, to provide information to those physicians responsible about the risk factors associated with its development, and to improve patient safety. METHODS: a descriptive cross-sectional observational study of prevalence. A total of 4, 964 patients from a Healthcare Area treated in one month with drugs with known risk were included in the study. Risk drugs, interactions and predisposing factors were identified. Physicians were provided with the list of patients with drugs with known risk, recommendations, and a questionnaire to know more risk factors, utility and clinical attitude. A descriptive statistical analysis was conducted. RESULTS: of the total number of patients in the Area, 3.2% were treated with drugs with known risk. 64.0% were women, 57.5% were older than 65 years and 39.6% had drug interactions. The mean number of risk factors per patient was 1.78 (CI 95%: 1.74-1.81). Antidepressants (41.2%) and antibiotics (40.4%) were the most commonly prescribed drugs with known risk. 25.4% of the physicians returned the questionnaire and reported the clinical attitude in 1, 073 patients: the drug with known risk was withdrawn in 289, the dose was reduced in 113, and an electrocardiogram was performed in 398. Physicians identified other risk factors: heart disease (17.9%) and hypo/hyperthyroidism (8.8%). CONCLUSIONS: the detected prevalence of prescription of drugs that prolong the QT interval is relevant, considering that the patients also had other risk factors. Their identification can improve the quality of care and patient safety. PMID- 26546938 TI - [Development of integrated support software for clinical nutrition]. AB - OBJECTIVES: to develop an integrated computer software application for specialized nutritional support, integrated in the electronic clinical record, which detects automatically and early those undernourished patients or at risk of developing undernourishment, determining points of opportunity for improvement and evaluation of the results. METHODS: the quality standards published by the Nutrition Work Group of the Spanish Society of Hospital Pharmacy (SEFH) and the recommendations by the Pharmacy Group of the Spanish Society of Parenteral and Enteral Nutrition (SENPE) have been taken into account. According to these quality standards, the nutritional support has to include the following healthcare stages or sub-processes: nutritional screening, nutritional assessment, plan for nutritional care, prescription, preparation and administration. RESULTS: this software allows to conduct, in an automated way, a specific nutritional assessment for those patients with nutritional risk, implementing, if necessary, a nutritional treatment plan, conducting follow-up and traceability of outcomes derived from the implementation of improvement actions, and quantifying to what extent our practice is close to the established standard. CONCLUSIONS: this software allows to standardize the specialized nutritional support from a multidisciplinary point of view, introducing the concept of quality control per processes, and including patient as the main customer. PMID- 26546934 TI - [The Caribbean Reference Centre for rare neuromuscular and neurological disorders]. PMID- 26546939 TI - [Validation of cold chain during distribution of parenteral nutrition]. AB - OBJECTIVE: this study aims to demonstrate the suitability of the process used to condition the extemporaneous mixtures of parenteral nutrition for distribution, considering the objective of preserving the cold chain during transport until it reaches the patient, necessary to ensure stability, effectiveness and safety of these mixtures. METHOD: concurrent validation, design and implementation of a protocol for evaluating the process of packaging and distribution of MNPE developed by a pharmaceutical laboratory. Running tests, according to predefined acceptance criteria. It is performed twice, in summer and on routes that require longer transfer time. Evaluation of conservation of temperature by monitoring the internal temperature values of each type of packaging, recorded by data loggers calibrated equipment. RESULTS: the different tests meet the established criteria. The collected data ensure the maintenance of the cold chain for longer than the transfer time to the most distant points. CONCLUSIONS: this study establishes the suitability of the processes to maintaining the cold chain for transfer from the laboratory to the patient pharmacist. Whereas the breaking of cold chain can cause changes of compatibility and stability of parenteral nutrition and failures nutritional support, this study contributes to patient safety, one of the relevant dimensions of quality of care the health. PMID- 26546940 TI - [Off-label use of oncology drugs: national survey results]. AB - PURPOSE: identify by means of a survey the off-label treatments more often used in the oncohaematology area, as well as to know the established procedures and criteria used to authorise those treatments. METHODS: a four-section survey was designed: 1) demographic data and hospital activity, 2) Off-label treatments protocol, 3) Approval criteria and 4) Off-label oncology treatments conducted during the last year. RESULTS: in 42.1% of the hospitals it's needed an authorisation before dispensing in more tan 80% of the treatments. The most influential factor in the approval-dispensation system is the available evidence. The consent of the hospital management with previous Pharmacy department's report was the most common authorisation procedure. 55.3% of the hospitals settled specific patient criteria to help the decision-making altogether with the available safety and efficacy data of the drug for the requested indication. In most centers a lower level of evidence is accepted if there are no therapeutic alternatives as well as in tumors of low prevalence. Most of the centers have not clearly established a criterion of effectiveness to consider a benefit as clinically relevant, nor the cost-effectiveness threshold for approving a FFT. CONCLUSIONS: there is a great variability in the off-label treatments use and also in the criteria used for its approval. PMID- 26546941 TI - Economic evaluation in collaborative hospital drug evaluation reports. AB - OBJECTIVE: economic evaluation is a fundamental criterion when deciding a drug's place in therapy. The MADRE method (Method for Assistance in making Decisions and Writing Drug Evaluation Reports) is widely used for drug evaluation. This method was developed by the GENESIS group of the Spanish Society of Hospital Pharmacy (SEFH), including economic evaluation. We intend to improve the economic aspects of this method. As for the direction to take, we have to first analyze our previous experiences with the current methodology and propose necessary improvements. METHOD: economic evaluation sections in collaboratively conducted drug evaluation reports (as the scientific society, SEFH) with the MADRE method were reviewed retrospectively. RESULTS: thirty-two reports were reviewed, 87.5% of them included an economic evaluation conducted by authors and 65.6% contained published economic evaluations. In 90.6% of the reports, a Budget impact analysis was conducted. The cost per life year gained or per Quality Adjusted Life Year gained was present in 14 reports. Twenty-three reports received public comments regarding the need to improve the economic aspect. Main difficulties: low quality evidence in the target population, no comparative studies with a relevant comparator, non-final outcomes evaluated, no quality of life data, no fixed drug price available, dosing uncertainty, and different prices for the same drug. CONCLUSIONS: proposed improvements: incorporating different forms of aid for non drug costs, survival estimation and adapting published economic evaluations; establishing criteria for drug price selection, decision-making in conditions of uncertainty and poor quality evidence, dose calculation and cost-effectiveness thresholds depending on different situations. PMID- 26546942 TI - [Vedolizumab in Crohn Disease genesis-sefh drug evaluation report]. PMID- 26546935 TI - [XII(th) Annual Meeting and 8(th) Master Price of the French Society of Myology]. PMID- 26546944 TI - [Switching therapy from natalizumab to fingolimod: reduction of the washout time?]. PMID- 26546945 TI - Effects of milk components and food additives on survival of three bifidobacteria strains in fermented milk under simulated gastrointestinal tract conditions. AB - BACKGROUND: In the dairy industry, probiotic strains of Bifidobacterium are introduced into the composition of traditional starter cultures intended for the production of fermented foods, or sometimes are the sole microflora responsible for the fermentation process. In order to be able to reach the intestines alive and fulfil their beneficial role, probiotic strains must be able to withstand the acidity of the gastric juices and bile present in the duodenum. OBJECTIVE: The paper reports effects of selected fermented milk components on the viability of three strains of bifidobacteria in fermented milk during subsequent incubation under conditions representing model digestive juices. DESIGN: The viability of the bifidobacterial cells was examined after a 3-h incubation of fermented milk under simulated gastric juice conditions and then after 5-h incubation under simulated duodenum juice conditions. The Bifidobacterium strains tested differed in their sensitivity to the simulated conditions of the gastrointestinal juices. RESULTS: Bifidobacterial cell viability in simulated intestinal juices was dependent on the strain used in our experiments, and product components acted protectively towards bifidobacterial cells and its dose. CONCLUSIONS: Bifidobacterial cells introduced into the human gastrointestinal tract as food ingredients have a good chance of survival during intestinal transit and to reach the large intestine thanks to the protective properties of the food components and depending on the strain and composition of the food. PMID- 26546943 TI - [Causal analysis and impact of a systematic error detected about consumption associated with trastuzumab]. AB - OBJECTIVE: determine the cause of the constant difference between the theoretical and real number of trastuzumab units consumed in an Intravenous Mixtures Unit. METHODS: was studied the manual and electronic full procedure about preparing mixtures with trastuzumab. Was performed by visual observation and review of quantitative monitoring data from the electronic preparation support and safe system of the application Farmis-Oncofarm(r). RESULTS: difference between the optimum volume of trastuzumab contained in the summary of product characteristics and the same included in Farmis_Oncofarm(r) was found. Also found a defect of the optimum volume of 10ml syringes used in the reconstitution vials process. CONCLUSIONS: the default in the optimal volume of 10ml syringes used in the reconstitution process increases the real consumed units of trastuzumab. This produces a significant economic impact calculated in an annual additional cost in approximately 46.508 ? without negative consequences for the patient. PMID- 26546946 TI - A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections. AB - BACKGROUND: It is a common medical practice to characterise an infection based on the causative agent and to adopt therapeutic and prevention strategies targeting the agent itself. However, from an epidemiological perspective, exposure to a microbe can be harmless to a host as a result of low-level exposure or due to host immune response, with opportunistic infection only occurring as a result of changes in the host, pathogen, or surrounding environment. METHODS: We have attempted to review systematically the key host, pathogen, and environmental factors that may significantly impact clinical outcomes of exposure to a pathogen, using Pseudomonas aeruginosa eye infection as a case study. RESULTS AND DISCUSSION: Extended contact lens wearing and compromised hygiene may predispose users to microbial keratitis, which can be a severe and vision-threatening infection. P. aeruginosa has a wide array of virulence-associated genes and sensing systems to initiate and maintain cell populations at the corneal surface and beyond. We have adapted the well-known concept of the epidemiological triangle in combination with the classic risk assessment framework (hazard identification, characterisation, and exposure) to develop a conceptual pathway based model that demonstrates the overlapping relationships between the host, the pathogen, and the environment; and to illustrate the key events in P. aeruginosa eye infection. CONCLUSION: This strategy differs from traditional approaches that consider potential risk factors in isolation, and hopefully will aid the identification of data and models to inform preventive and therapeutic measures in addition to risk assessment. Furthermore, this may facilitate the identification of knowledge gaps to direct research in areas of greatest impact to avert or mitigate adverse outcomes of infection. PMID- 26546949 TI - Cases of liver failure linked to "fat-burning" supplement. PMID- 26546948 TI - Examine the patient, not just the evidence. PMID- 26546952 TI - Influenza vaccination: What's new this season? AB - One IIV trivalent product can now be given with a needle-free jet injector. A recombinant vaccine formulation is available for those who have egg allergy. The algorithm for dosing in children now asks just one question. PMID- 26546953 TI - Recurrent vesicular rash over the sacrum. PMID- 26546950 TI - Zeroing in on the cause of your patient's facial pain. AB - The overlapping characteristics of facial pain can make it difficult to pinpoint the cause. This article, with a handy at-a-glance table, can help. PMID- 26546947 TI - Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers. AB - Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul(r) MCM C8/Capmul(r) PG8, Tween(r) 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel(r) layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend(r) tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-infinity) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa. PMID- 26546954 TI - Clinical Inquiry: Does qHPV vaccine prevent anal intraepithelial neoplasia and condylomata in men? AB - Yes. Quadrivalent human papillomavirus (qHPV) vaccine reduces rates of anal intraepithelial neoplasia (AIN) by 50% to 54%, and persistent anal infection by 59%, associated with the 4 types of HPV in the vaccine (6, 11, 16, and 18) in young men who have sex with men (MSM); it also reduces external genital lesions by 66%, and persistent HPV infection associated with the same 4 HPV types by 48 to 59% in all young men, heterosexual men, and MSM. PMID- 26546951 TI - Osteoporosis: What about men? AB - Men sustain up to 40% of osteoporotic fractures, with potentially fatal results. But because osteoporosis is largely viewed as a women's disease, its presence in men is often missed. PMID- 26546955 TI - Hepatitis C: How to fine-tune your approach. AB - Advances in drug therapy have made it possible to cure HCV infection. This article describes how best to screen, diagnose, and counsel these patients. PMID- 26546956 TI - Tuberculosis testing: Which patients, which test? AB - The most appropriate test to identify latent TB depends on the patient's risk for developing active TB and other factors. This review provides practical guidance on who to test, how, and when. PMID- 26546957 TI - Clinical Inquiry: How effective are opioids for chronic low back pain? AB - Short-term (<4 months) treatment with opioids provides modest relief of chronic low back pain, but only minimal improvement in function compared with placebo. PMID- 26546958 TI - Med students: Look up from your EMRs. AB - It frightens me to think what might have happened during my hospital stay if I hadn't provided information that wasn't required by the EMR. PMID- 26546959 TI - Hot flashes and night sweats . amenorrhea . positive home pregnancy test . Dx? AB - Hormone therapy and supplemental calcium and vitamin D are recommended for women with primary ovarian insufficiency to help prevent loss of bone density and other negative effects of low estrogen. PMID- 26546961 TI - Fibromyalgia . anxiety/depression . urinary retention . Dx? PMID- 26546960 TI - Clinical Inquiry: Which interventions can increase breastfeeding duration? AB - Breastfeeding support, beyond standard care, from lay people or professionals increases both short- and long-term breastfeeding duration. PMID- 26546962 TI - Major Depressive Disorder in the Primary Care Setting: Strategies to Achieve Remission and Recovery. PMID- 26546963 TI - Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): A review of 47 cases. AB - OBJECTIVE: Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. METHODS: We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. RESULTS: Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2 months (range, 0.1 to 210.7) with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. CONCLUSION: Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations. PMID- 26546964 TI - A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer. AB - OBJECTIVES: Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. METHODS: Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan Meier estimate; the log-rank test was used to compare survival curves. RESULTS: Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2 3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. CONCLUSION: IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities. PMID- 26546965 TI - Is the inflammasome relevant for epithelial cell function? AB - Inflammasomes are intracellular protein complexes that sense microbial components and damage of infected cells. Following activation by molecules released by pathogens or injured cells, inflammasomes activate caspase-1, allowing secretion of the pro-inflammatory cytokines IL-1beta and IL-18 from innate immune cells. Inflammasomes are also expressed in epithelial cells, where their function has attracted less attention. Nonetheless, depending on the tissue, epithelial inflammasomes can mediate inflammation, wound healing, and pain sensitivity. We review here recent findings on inflammasomes found in epithelial tissues, highlighting the importance of these protein complexes in the response of epithelial tissues to microbial infections. PMID- 26546968 TI - Ultramicroscopy reveals that senescence induces in-situ and vacuolar degradation of plastoglobules in aging watermelon leaves. AB - The dynamics of plastoglobules in chloroplasts in aging watermelon leaves were examined by means of transmission electron microscopy, with the aim to understand the intracellular sites for the degradation of plastoglobules in response to leaf senescence. Plastoglobules in chloroplasts in aging leaves with 40% loss of chlorophyll increased drastically in number and size in comparison with young and mature leaves. As senescence advanced, plastoglobules underwent degradation within chloroplasts, or were secreted outside chloroplasts. There were two distinct types of secretion. One type was that chloroplasts protruded to form plastoglobule-containing vesicles and, as the vesicles were detached from chloroplasts, plastoglobules were carried outside chloroplasts. The other type was that plastoglobules squeezed out through the chloroplast envelope into cytoplasm. Lipid droplets were present in the vacuole and underwent degradation therein. Lipid droplets in the vacuole shared similar ultramicroscopic appearance with plastoglobules in chloroplasts, indicating that plastoglobules were engulfed and degraded by the vacuole after they were secreted outside chloroplasts. These results suggested that senescence induces both in-situ and vacuolar degradation of plastoglobules in aging watermelon leaves. PMID- 26546967 TI - The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches. AB - The interest in effects of strontium (Sr) on bone has greatly increased in the last decade due to the development of the promising drug strontium ranelate. This drug is used for treating osteoporosis, a major bone disease affecting hundreds of millions of people worldwide, especially postmenopausal women. The novelty of strontium ranelate compared to other treatments for osteoporosis is its unique effect on bone: it simultaneously promotes bone formation by osteoblasts and inhibits bone resorption by osteoclasts. Besides affecting bone cells, treatment with strontium ranelate also has a direct effect on the mineralized bone matrix. Due to the chemical similarities between Sr and Ca, a topic that has long been of particular interest is the incorporation of Sr into bones replacing Ca from the mineral phase, which is composed by carbonated hydroxyapatite nanocrystals. Several groups have analyzed the mineral produced during treatment; however, most analysis were done with relatively large samples containing numerous nanocrystals, resulting thus on data that represents an average of many crystalline domains. The nanoscale analysis of the bone apatite crystals containing Sr has only been described in a few studies. In this study, we review the current knowledge on the effects of Sr on bone mineral and discuss the methodological approaches that have been used in the field. In particular, we focus on the great potential that advanced microscopy and microanalytical techniques may have on the detailed analysis of the nanostructure and composition of bone apatite nanocrystals produced during treatment with strontium ranelate. PMID- 26546966 TI - Oligodendrocyte progenitor programming and reprogramming: Toward myelin regeneration. AB - Demyelinating diseases such as multiple sclerosis (MS) are among the most disabling and cost-intensive neurological disorders. The loss of myelin in the central nervous system, produced by oligodendrocytes (OLs), impairs saltatory nerve conduction, leading to motor and cognitive deficits. Immunosuppression therapy has a limited efficacy in MS patients, arguing for a paradigm shift to strategies that target OL lineage cells to achieve myelin repair. The inhibitory microenvironment in MS lesions abrogates the expansion and differentiation of resident OL precursor cells (OPCs) into mature myelin-forming OLs. Recent studies indicate that OPCs display a highly plastic ability to differentiate into alternative cell lineages under certain circumstances. Thus, understanding the mechanisms that maintain and control OPC fate and differentiation into mature OLs in a hostile, non-permissive lesion environment may open new opportunities for regenerative therapies. In this review, we will focus on 1) the plasticity of OPCs in terms of their developmental origins, distribution, and differentiation potentials in the normal and injured brain; 2) recent discoveries of extrinsic and intrinsic factors and small molecule compounds that control OPC specification and differentiation; and 3) therapeutic potential for motivation of neural progenitor cells and reprogramming of differentiated cells into OPCs and their likely impacts on remyelination. OL-based therapies through activating regenerative potentials of OPCs or cell replacement offer exciting opportunities for innovative strategies to promote remyelination and neuroprotection in devastating demyelinating diseases like MS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). PMID- 26546969 TI - Statin therapy and plasma cortisol concentrations: A systematic review and meta analysis of randomized placebo-controlled trials. AB - This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations. Following a systematic search in Medline, SCOPUS, Web of Science and Google Scholar databases (by up to March 01, 2015), 7 eligible RCTs were selected. Random-effects meta-analysis suggested a significant increase in plasma cortisol concentrations following statin therapy (WMD: 6.34%, 95% CI: 1.80, 10.87, p=0.006). Subgroup analysis confirmed the significance of the effect with lipophilic statins comprising atorvastatin, simvastatin, and lovastatin (WMD: 7.00%, 95% CI: 2.21, 11.79, p=0.004) but not with hydrophilic statins (rosuvastatin and pravastatin) (WMD: 0.60%, 95% CI: 13.46, 14.66, p=0.933). In the meta-regression analysis, changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration. Results of this meta-analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy. PMID- 26546970 TI - The use of ranolazine in non-anginal cardiovascular disorders: A review of current data and ongoing randomized clinical trials. AB - Ranolazine has characteristic properties of a selective inhibitor of the inward sodium current. It is primarily indicated as an anti-anginal agent in patients with coronary artery disease and chronic stable angina. Recently, ranolazine has been noted to possibly impart beneficial effects in various other cardiac conditions, including new-onset, paroxysmal, and chronic atrial fibrillation, post-operative atrial fibrillation, ventricular arrhythmias, post revascularization coronary artery disease, chemotherapeutic cardiotoxicity, and diastolic and microvascular dysfunction. Herein, we present a review of the current clinical evidence describing the adjunctive or synergistic effects of ranolazine in non-angina related cardiovascular disorders, and include a discussion of the ongoing randomized trials investigating the therapeutic potential of ranolazine in a variety of cardiovascular diseases. PMID- 26546972 TI - Bio-inspired polymer envelopes around adenoviral vectors to reduce immunogenicity and improve in vivo kinetics. AB - Adenoviral vectors have attracted substantial interest for systemic tumor gene therapy, but further work is needed to reduce their immunogenicity and alter their biodistribution before they can be used in the clinic. Here we describe a bio-inspired, cleavable PEGylated beta-cyclodextrin-polyethyleneimine conjugate (CDPCP) that spontaneously coats adenovirus in solution. This cleavable PEG coating reduces the innate and adaptive immunogenicity of adenovirus particles, as well as improves their biodistribution away from the liver and into the tumor. Insertion of a matrix metalloproteinase substrate sequence into the conjugate allows PEG cleavage at the tumor site, simultaneously reducing liver biodistribution and increasing transgene expression in tumors, thereby avoiding the "PEG dilemma". Cationic beta-cyclodextrin-PEI not only provides electrostatic attraction to promote envelope attachment to the viral capsid, but it also improves vector internalization and transduction after PEG cleavage. These results suggest that CDPCP may help expand the use of adenoviral vectors in cancer gene therapy. STATEMENT OF SIGNIFICANCE: The synthesized beta-cyclodextrin PEI-MMP-cleavable-PEG polymer (CDPCP), held great potential for gene therapy when applied for adenovirus coating. The beta-cyclodextrin-PEI provided a powerful electrostatic attraction to attach the whole polymer onto the viral capsid, while the MMPs-cleavable PEG reduced innate and adaptive immunogenicity and improved the biodistribution of adenovirus vectors due to the tumor-specific enzyme triggered PEG cleavage. More importantly, an ingenious cooperation between the two components could solve the PEG dilemma. The CDPCP/Ad complexes exhibited a comprehensive and valued profile to be a candidate vector for future tumor gene therapy, we believe the current investigation on this kind of biomaterial may be of particular interest to the readership of Acta biomaterialia. PMID- 26546971 TI - How many TCR clonotypes does a body maintain? AB - We consider the lifetime of a T cell clonotype, the set of T cells with the same T cell receptor, from its thymic origin to its extinction in a multiclonal repertoire. Using published estimates of total cell numbers and thymic production rates, we calculate the mean number of cells per TCR clonotype, and the total number of clonotypes, in mice and humans. When there is little peripheral division, as in a mouse, the number of cells per clonotype is small and governed by the number of cells with identical TCR that exit the thymus. In humans, peripheral division is important and a clonotype may survive for decades, during which it expands to comprise many cells. We therefore devise and analyse a computational model of homeostasis of a multiclonal population. Each T cell in the model competes for self pMHC stimuli, cells of any one clonotype only recognising a small fraction of the many subsets of stimuli. A constant mean total number of cells is maintained by a balance between cell division and death, and a stable number of clonotypes by a balance between thymic production of new clonotypes and extinction of existing ones. The number of distinct clonotypes in a human body may be smaller than the total number of naive T cells by only one order of magnitude. PMID- 26546973 TI - In vitro maturation of large-scale cardiac patches based on a perfusable starter matrix by cyclic mechanical stimulation. AB - The ultimate goal of tissue engineering is the generation of implants similar to native tissue. Thus, it is essential to utilize physiological stimuli to improve the quality of engineered constructs. Numerous publications reported that mechanical stimulation of small-sized, non-perfusable, tissue engineered cardiac constructs leads to a maturation of immature cardiomyocytes like neonatal rat cardiomyocytes or induced pluripotent stem cells/embryonic stem cells derived self-contracting cells. The aim of this study was to investigate the impact of mechanical stimulation and perfusion on the maturation process of large-scale (2.5*4.5cm), implantable cardiac patches based on decellularized porcine small intestinal submucosa (SIS) or Biological Vascularized Matrix (BioVaM) and a 3 dimensional construct containing neonatal rat heart cells. Application of cyclic mechanical stretch improved contractile function, cardiomyocyte alignment along the stretch axis and gene expression of cardiomyocyte markers. The development of a complex network formed by endothelial cells within the cardiac construct was enhanced by cyclic stretch. Finally, the utilization of BioVaM enabled the perfusion of the matrix during stimulation, augmenting the beneficial influence of cyclic stretch. Thus, this study demonstrates the maturation of cardiac constructs with clinically relevant dimensions by the application of cyclic mechanical stretch and perfusion of the starter matrix. STATEMENT OF SIGNIFICANCE: Considering the poor endogenous regeneration of the heart, engineering of bioartificial cardiac tissue for the replacement of infarcted myocardium is an exciting strategy. Most techniques for the generation of cardiac tissue result in relative small-sized constructs insufficient for clinical applications. Another issue is to achieve cardiomyocytes and tissue maturation in culture. Here we report, for the first time, the effect of mechanical stimulation and simultaneous perfusion on the maturation of cardiac constructs of clinical relevant dimensions, which are based on a perfusable starter matrix derived from porcine small intestine. In response to these stimuli superior organization of cardiomyocytes and vascular networks was observed in contrast to untreated controls. The study provides substantial progress towards the generation of implantable cardiac patches. PMID- 26546975 TI - CRISPR/Cas9: An inexpensive, efficient loss of function tool to screen human disease genes in Xenopus. AB - Congenital malformations are the major cause of infant mortality in the US and Europe. Due to rapid advances in human genomics, we can now efficiently identify sequence variants that may cause disease in these patients. However, establishing disease causality remains a challenge. Additionally, in the case of congenital heart disease, many of the identified candidate genes are either novel to embryonic development or have no known function. Therefore, there is a pressing need to develop inexpensive and efficient technologies to screen these candidate genes for disease phenocopy in model systems and to perform functional studies to uncover their role in development. For this purpose, we sought to test F0 CRISPR based gene editing as a loss of function strategy for disease phenocopy in the frog model organism, Xenopus tropicalis. We demonstrate that the CRISPR/Cas9 system can efficiently modify both alleles in the F0 generation within a few hours post fertilization, recapitulating even early disease phenotypes that are highly similar to knockdowns from morpholino oligos (MOs) in nearly all cases tested. We find that injecting Cas9 protein is dramatically more efficacious and less toxic than cas9 mRNA. We conclude that CRISPR based F0 gene modification in X. tropicalis is efficient and cost effective and readily recapitulates disease and MO phenotypes. PMID- 26546974 TI - Neural crest requires Impdh2 for development of the enteric nervous system, great vessels, and craniofacial skeleton. AB - Mutations that impair the proliferation of enteric neural crest-derived cells (ENCDC) cause Hirschsprung disease, a potentially lethal birth defect where the enteric nervous system (ENS) is absent from distal bowel. Inosine 5' monophosphate dehydrogenase (IMPDH) activity is essential for de novo GMP synthesis, and chemical inhibition of IMPDH induces Hirschsprung disease-like pathology in mouse models by reducing ENCDC proliferation. Two IMPDH isoforms are ubiquitously expressed in the embryo, but only IMPDH2 is required for life. To further understand the role of IMPDH2 in ENS and neural crest development, we characterized a conditional Impdh2 mutant mouse. Deletion of Impdh2 in the early neural crest using the Wnt1-Cre transgene produced defects in multiple neural crest derivatives including highly penetrant intestinal aganglionosis, agenesis of the craniofacial skeleton, and cardiac outflow tract and great vessel malformations. Analysis using a Rosa26 reporter mouse suggested that some or all of the remaining ENS in Impdh2 conditional-knockout animals was derived from cells that escaped Wnt1-Cre mediated DNA recombination. These data suggest that IMPDH2 mediated guanine nucleotide synthesis is essential for normal development of the ENS and other neural crest derivatives. PMID- 26546976 TI - The transcription regulation analysis of Ctenopharyngodon idellus PKR and PKZ genes. AB - Protein kinase R (PKR), the double-stranded RNA-activated protein kinase, exists in mammalian and fish. PKZ, a PKR-like protein kinase containing Z-DNA binding domains, just exists in fish. PKR and PKZ work synergistically in the antiviral defense by inhibiting intracellular protein translation. The transcriptional factor IRF3 (interferon regulatory factor 3) acts as a key regulator of type I IFN (Interferon) and ISG (interferon stimulated gene). On the basis of the cloned CiIRF3 previously, CiIRF3 with His-tag was over-expressed in BL21 Escherichia coli, and the expressed protein was purified by affinity chromatography with Ni NTA His-Bind Resin. In this study, we have demonstrated that grass carp (Ctenopharyngodon idellus) PKR (CiPKR) and PKZ (CiPKZ) genes were inducible by Poly I:C in C. idella kidney (CIK) cells. So, they might be implicated in the intracellular antiviral activity. To understand the up regulatory mechanism of CiPKR and CiPKZ genes upon virus induction, we constructed wild type (pGL3-CiPKR luc and pGL3-CiPKZ-luc) and the mutant (pGL3-CiPKR-nISRE-luc and pGL3-CiPKZ-nISRE luc) reporter gene vectors according to the promoter sequences of CiPKR (KJ704845) and CiPKZ (KJ704844). In vitro, gel mobility shift assays demonstrated that CiIRF3 can combine CiPKR and CiPKZ promoters with high affinity. However, CiIRF3 bound to the mutants CiPKR-nISRE and CiPKZ-nISRE faintly. Whereafter, the recombinant plasmids of pGL3-CiPKR-luc, pGL3-CiPKZ-luc were transiently co transfected with pcDNA3.1-CiIRF3, pcDNA3.1-CiIRF7 respectively into CIK cells. Cell transfection assays indicated that CiIRF3 and CiIRF7 up-regulated the transcriptional level of CiPKR and CiPKZ. The results also revealed that the consensus sequence of ISRE (interferon stimulated response element) is an important regulatory element for the transcriptional initiation of CiPKR and CiPKZ. PMID- 26546977 TI - Bisphenol A-induced epithelial to mesenchymal transition is mediated by cyclooxygenase-2 up-regulation in human endometrial carcinoma cells. AB - Many studies have highlighted the correlation between the increase of bisphenol A (BPA) level in the environment and the incidence of tumor in humans. In human carcinogenesis, the overexpression of cyclooxygenase-2 (COX-2) and epithelial mesenchymal transition (EMT) are closely related with tumor development. In this study, human endometrial carcinoma cells line (RL95-2) was used to investigate whether BPA can induce EMT and COX-2 expression. The results show that BPA increased growth rate and colony-forming efficiency in a dose-dependent manner, induced EMT and COX-2 gene expression and promoted the migration and invasion ability of RL95-2 cells. Furthermore, our study showed that the expression of COX 2 was essential for BPA-induced cell migration and invasion. The results of this study provide new insights into the mechanism of endometrial cancer cell growth and invasion and potential therapeutic strategy. PMID- 26546978 TI - Assessment of cervical passage of vital dyes in pregnant, nonpregnant, and mated rats and mice. AB - Risk assessment for indirect exposure to small molecule pharmaceuticals in semen to the conceptus has traditionally been handled by calculations based on assumptions that any embryo-fetal exposure would be secondary to maternal absorption and redistribution. This study was designed to assess the potential for transcervical passage of drugs from semen. Reproductive tracts of rodents were examined following vaginal dosing with vital dyes during the estrous cycle, mating, and pregnancy. Toluidine Blue was not observed beyond the cervix after vaginal administration in pregnant rats; additionally, it did not pass the cervix in rats during any phase of estrous. In order to address the effects of semen, rats were dosed at receptivity and mated. Vital dyes were not visually evident in the uterus despite vaginal and sperm plug staining. This study provides evidence that direct transcervical passage is not a substantial route of direct embryo fetal exposure for small molecule drugs in semen. PMID- 26546979 TI - Spread of pedigree versus genetic ancestry in spatially distributed populations. AB - Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ~ t rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models. PMID- 26546980 TI - Rates of lymph node metastasis and survival in T1a gastric adenocarcinoma in Western populations. AB - BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are widely accepted in Asia for treatment of early gastric cancer (EGC). Few studies have examined lymph node (LN) metastasis of EGC in Western populations. We sought to examine EGC and LN metastasis in a heterogeneous Western population. METHODS: Patients with surgically resected, histologically confirmed American Joint Committee on Cancer T1a gastric adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2002 to 2012. Patients were excluded if they had stage IV disease, had multiple primary cancers, or received neoadjuvant therapy. Rates of LN metastasis were calculated, and survival analyses were performed. RESULTS: Of 923 patients in the cohort, 72 (7.8%) had at least 1 positive LN on final pathology. When stratified by race, Asian/Pacific Islanders (APIs) demonstrated the lowest rate of LN metastases (n = 17/327, 5.2%), followed by Hispanics (n = 12/171, 7.0%), whites (n = 27/278, 9.7%), and blacks (n = 16/147, 10.9%). The highest rates of stage IA disease were observed in API (93.9%) and Hispanic (92.4%) patients, followed by white (89.9%) and black (87.1%) patients (P = .04). Survival analysis of T1a gastric cancer patients by race/ethnicity showed that 5-year overall survival was highest for API patients (API, 88%; Hispanic, 81%; black, 79%; and white, 77%; P < .01). CONCLUSIONS: The rate of LN metastasis in T1a gastric cancers in the United States is higher than the rates reported in Asia. Survival outcomes in T1a gastric cancers varied significantly by race, suggesting that definitive endoscopic treatment may not be appropriate for all patients in the United States. PMID- 26546981 TI - Outcomes of ERCP in Billroth II gastrectomy patients. AB - BACKGROUND AND AIMS: ERCP is a difficult procedure to perform in Billroth II gastrectomy patients because of altered anatomy. We investigated the outcomes and risk factors for adverse events with ERCP using a cap-fitted forward-viewing endoscope with endoscopic papillary balloon dilation (EPBD) in Billroth II gastrectomy patients. METHODS: The records for Billroth II gastrectomy patients who underwent ERCP using a cap-fitted forward-viewing endoscope with EPBD at 5 institutions between August 2008 and April 2014 were retrospectively reviewed. The outcomes and risk factors for adverse events resulting from this treatment were analyzed. RESULTS: In total, 165 patients were identified. ERCP was technically successful in 144 patients (87.3%) and clinically successful in 141 patients (85.5%). Adverse events occurred in 38 patients (23.0%): perforation in 3 cases (1.8%), pancreatitis in 13 cases (7.9%), and asymptomatic hyperamylasemia in 22 patients (13.3%). In univariate analysis, >=2 ERCP sessions, periampullary diverticulum, and common bile duct (CBD) stone size >= 12 mm were found to be associated with ERCP-related adverse events. In multivariate analysis, >=2 ERCP sessions (odds ratio [OR], 4.762; 95% confidence interval [CI], 1.472-15.402; P = .009) and a CBD stone size >= 12 mm (OR, 3.213; 95% CI, 1.140-9.057; P = .027) were significant. CONCLUSIONS: ERCP using a cap-fitted forward-viewing endoscope with EPBD is feasible in Billroth II gastrectomy patients. In patients with >=2 ERCP sessions or a CBD stone size >= 12 mm, special attention should be paid to the possible occurrence of significant adverse events. PMID- 26546982 TI - Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies. AB - The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. PMID- 26546983 TI - Manipulating mammalian cell by phase transformed titanium surface fabricated through ultra-short pulsed laser synthesis. AB - Developing cell sensitive indicators on interacting substrates that allows specific cell manipulation by a combination of physical, chemical or mechanical cues is a challenge for current biomaterials. Hence, various fabrication approaches have been created on a variety of substrates to mimic or create cell specific cues. However, to achieve cell specific cues a multistep process or a post-chemical treatment is often necessitated. So, a simple approach without any chemical or biological treatment would go a long way in developing bio functionalized substrates to effectively modulate cell adhesion and interaction. The present investigation is aimed to study the manipulative activity induced by phase transformed titanium surface. An ultra-short laser is used to fabricate the phase transformed titanium surface where a polymorphic titanium oxide phases with titanium monoxide (TiO), tri-titanium oxide (Ti3O) and titanium dioxide (TiO2) have been synthesized on commercially pure titanium. Control over oxide phase transformed area was demonstrated via a combination of laser scanning time (laser pulse interaction time) and laser pulse widths (laser pulse to pulse separation time). The interaction of phase transformed titanium surface with NIH3T3 fibroblasts and MC3T3-E1 osteoblast cells developed a new bio-functionalized platforms on titanium based biomaterials to modulate cell migration and adhesion. The synthesized phase transformed titanium surface on the whole appeared to induce directional cues for cell migration with unique preferential cell adhesion unseen by other fabrication approaches. The precise bio-functionalization controllability exhibited during fabrication offers perceptible edge for developing a variety of smart bio-medical devices, implants and cardiovascular stents where the need in supressing specific cell adhesion and proliferation is of great demand. PMID- 26546984 TI - Isolation and characterization of human islet stellate cells. AB - BACKGROUND AND AIMS: We have previously demonstrated that islet stellate cells (ISCs) exhibiting a similar phenotype to classical pancreatic stellate cells (PSCs) could be isolated from rat islets, where they may contribute to islet fibrosis in type 2 diabetes mellitus (T2DM). This study was designed to determine whether human islets also contain ISC. MATERIALS AND METHODS: Using standard explants techniques, human ISCs were enriched from freshly isolated human islets. Immunofluorescence visualization of markers for PSCs(alpha-smooth muscle actin;alpha-SMA), desmin, vimentin, glial fibrillary acidic protein (GFAP) was used to characterize the human ISC. Cell counting kit-8 (CCK-8) was used to assess the proliferation of ISC. The wound-healing assay and the transwell migration were used to assess the migration capacity of ISC. Immunofluorescence against collagen typesI (col-I), collagen typesIII (col-III) and fibronectin (FN) was performed to identify extracellular matrix (ECM) component synthesized by ISC. Adipogenic and osteogenic differentiation were tried to detected stem cell potential. RESULTS: In culture, ISC with triangular shape grow out from human islets. The passaged ISC expressed alpha-SMA, desmin, vimentin, GFAP and was positive for col-I, col-III and FN. The proliferation and migration ability of ISC was significantly slower than those of PSC. And both the human PSC and ISC were able to differentiate in vitro into adipocyte- and osteoblast-like cells. CONCLUSION: Similar to our previous rat experiment, the current study shows that human islets also contain ISC which is phenotypically similar but not identical to human PSC. PMID- 26546986 TI - Filtering mechanical chest compression artefacts from out-of-hospital cardiac arrest data. AB - AIM: Filtering techniques to remove manual compression artefacts from the ECG have not been incorporated to defibrillators to diagnose the rhythm during cardiopulmonary resuscitation. Mechanical and manual compression artefacts may be very different. The aim of this study is to characterize the compression artefact caused by the LUCAS 2 device and to evaluate whether filtering the LUCAS 2 artefact results in an accurate rhythm analysis. METHODS: A dataset of 1045 segments were obtained from 230 out-of-hospital cardiac arrest (OHCA) patients after LUCAS 2 activation. Rhythms were 201 shockable, 270 asystole and 574 organized. Segments during asystole were used to characterize the artefact in time and frequency domains. Three filtering methods, a comb filter and two adaptive filters, were used to remove the mechanical compression artefact. The filtered ECG was then diagnosed with a shock decision algorithm from a defibrillator. RESULTS: When compared to the manual compression artefact, the LUCAS 2 artefact presented a similar amplitude (1.2 mV, p-value 0.26), fixed frequency (101.7 min(-1)), more harmonic components, smaller spectral dispersion, and a more regular waveform (p-val <3 * 10(-7)). The sensitivity (SE) and specificity (SP) before filtering the LUCAS 2 artefact were 52.8% (90% low CI, 46.0%) and 81.5% (79.0%), respectively. For the best filter, SE and SP after filtering were 97.9% (95.7%) and 84.1% (82.0%), respectively. Optimal filters require more harmonics and smaller bandwidths than for manual compressions. CONCLUSION: Filtering resulted in a large increase in SE and small increase in SP. Despite differences in artefact characteristics between manual and mechanical compressions, filtering the LUCAS 2 compression artefact results in SE/SP values comparable to those obtained for manual compression artefacts. The SP is still below the 95% recommended by the American Heart Association. PMID- 26546985 TI - Regulation of invadopodia by mechanical signaling. AB - Mechanical rigidity in the tumor microenvironment is associated with a high risk of tumor formation and aggressiveness. Adhesion-based signaling driven by a rigid microenvironment is thought to facilitate invasion and migration of cancer cells away from primary tumors. Proteolytic degradation of extracellular matrix (ECM) is a key component of this process and is mediated by subcellular actin-rich structures known as invadopodia. Both ECM rigidity and cellular traction stresses promote invadopodia formation and activity, suggesting a role for these structures in mechanosensing. The presence and activity of mechanosensitive adhesive and signaling components at invadopodia further indicates the potential for these structures to utilize myosin-dependent forces to probe and remodel their ECM environments. Here, we provide a brief review of the role of adhesion based mechanical signaling in controlling invadopodia and invasive cancer behavior. PMID- 26546987 TI - Comparative Effect of Power Training and High-Speed Yoga on Motor Function in Older Patients With Parkinson Disease. AB - OBJECTIVES: To compare the effects of power training (PWT) and a high-speed yoga program on physical performances in older patients with Parkinson disease (PD), and to test the hypothesis that both training interventions would attenuate PD symptoms and improve physical performance. DESIGN: Randomized controlled trial. SETTING: A laboratory of neuromuscular research and active aging. PARTICIPANTS: Patients with PD (N=41; mean age +/- SD, 72.2 +/- 6.5y). INTERVENTIONS: Two high speed exercise interventions (specifically designed yoga program and PWT) were given for 12 weeks (twice a week), and 1 nonexercise control group. MAIN OUTCOME MEASURES: Unified Parkinson Disease Rating Scale motor score (UPDRSMS), Berg Balance Scale (BBS), Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go, functional reach, single leg stance (SLS), postural sway test, 10-m usual and maximal walking speed tests, 1 repetition maximum (RM), and peak power (PPW) for leg press. RESULTS: For the posttests, both training groups showed significant improvements (P<.05) in all physical measurements except functional reach on the more affected side, SLS, and postural sway compared with the pretests, and significantly better scores for UPDRSMS, BBS, Mini-BESTest, Timed Up and Go, functional reach on the less affected side, 10-m usual and maximal walking speed tests, 1RM, and PPW than controls, with no differences detected between the yoga program and PWT. CONCLUSIONS: Both the specially designed yoga program and PWT programs can significantly improve physical performance in older persons with PD. PMID- 26546988 TI - Metabolic syndrome and social deprivation: results of a French observational multicentre survey. AB - BACKGROUND: Deprivation, a process that prevents people to assume their social responsibilities, is a main cause of inequalities in health. Metabolic syndrome has a growing prevalence in France. OBJECTIVES: To assess the association between deprivation and the metabolic syndrome and to identify the most relevant waist circumference cut-off point. METHODS: A cross-sectional multicentre study was carried out of data extracted from health examination centres of two French areas in 2008. The harmonized definition of the metabolic syndrome contained five criteria with two thresholds for waist circumference. Deprivation was calculated by the Evaluation of Deprivation and Inequalities in Health Examination Centres score (EPICES). Eligible patients were at least 16 years old. The methodology of time to event analysis was used on patients having two criteria to identify the most relevant waist circumference threshold, taking waist circumference as event and computing it as a continuous variable. The median corresponded to the waist circumference threshold for which half of the patients switched from two to three criteria and so metabolic syndrome. RESULTS: Of the 32374 persons included in the study, 39.4% were socially deprived. The prevalence of the metabolic syndrome varied from 16.3% to 22.2% in the overall sample depending on the published waist circumference thresholds chosen. Deprivation was an independent factor associated with the metabolic syndrome. The cut-off point for waist circumference was between 95 and 99 cm for men and 88 and 97 cm for women. CONCLUSION: Deprivation is associated with a higher prevalence of the metabolic syndrome. The most relevant threshold for waist circumference could be 94 cm for men and 88 cm for women. PMID- 26546990 TI - Maximizing the Volume of Latissimus Dorsi Flap in Autologous Breast Reconstruction with Simultaneous Multisite Fat Grafting. AB - BACKGROUND: The pedicled latissimus dorsi (LD) flap serves an important function in breast reconstruction, but its utility is limited by its inability to provide sufficient breast volume. OBJECTIVES: The purpose of this preliminary report was to review the techniques and outcomes of utilizing fat-grafted, volume-enhanced LD flap transfer with fat grafting recipient sites in autologous breast reconstruction. METHODS: A retrospective study was performed of 10 patients (14 breasts) who underwent autologous breast reconstruction utilizing the LD flap transfer technique and simultaneous fat grafting between August 2012 and September 2014. Multilayer, multisite fat grafting was performed to the LD muscle, LD skin paddle, mastectomy skin flaps, and the pectoralis major and serratus muscles simultaneously with the LD flap transfer. RESULTS: Three patients underwent an immediate breast reconstruction, four underwent a delayed breast reconstruction, and four underwent a tertiary breast reconstruction following previously failed breast reconstructions (one patient underwent each of the first two procedures, one on each breast). The average age of the patients was 55 years (range, 39-76 years), the average body mass index of the patients was 29.3 (range, 19.6-39.9), and the average fat grafting volume for the patients was 176 mL (range, 50-300 mL). There was 100% flap survival and complete wound healing. No seroma or fat grafting-related complications were clinically detected. Three patients required additional fat grafting. CONCLUSIONS: The fat grafted, volume-enhanced LD flap procedure with fat grafting recipient sites offers a simple and safe technique for autologous breast reconstruction, with low morbidity and fast recovery. It can be a useful alternative to utilizing abdomen based flaps in autologous breast reconstruction or could be performed to salvage both implant-based and free-flap breast reconstructions. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26546989 TI - Single-particle cryo-EM data acquisition by using direct electron detection camera. AB - Recent advances in single-particle electron cryo-microscopy (cryo-EM) were largely facilitated by the application of direct electron detection cameras. These cameras feature not only a significant improvement in detective quantum efficiency but also a high frame rate that enables images to be acquired as 'movies' made of stacks of many frames. In this review, we discuss how the applications of direct electron detection cameras in cryo-EM have changed the way the data are acquired. PMID- 26546991 TI - Therapeutic applications of reconstituted HDL: When structure meets function. AB - Reconstituted forms of HDL (rHDL) are under development for infusion as a therapeutic approach to attenuate atherosclerotic vascular disease and to reduce cardiovascular risk following acute coronary syndrome and ischemic stroke. Currently available rHDL formulations developed for clinical use contain apolipoprotein A-I (apoA-I) and one of the major lipid components of HDL, either phosphatidylcholine or sphingomyelin. Recent data have established that quantitatively minor molecular constituents of HDL particles can strongly influence their anti-atherogenic functionality. Novel rHDL formulations displaying enhanced biological activities, including cellular cholesterol efflux, may therefore offer promising prospects for the development of HDL-based, anti atherosclerotic therapies. Indeed, recent structural and functional data identify phosphatidylserine as a bioactive component of HDL; the content of phosphatidylserine in HDL particles displays positive correlations with all metrics of their functionality. This review summarizes current knowledge of structure-function relationships in rHDL formulations, with a focus on phosphatidylserine and other negatively-charged phospholipids. Mechanisms potentially underlying the atheroprotective role of these lipids are discussed and their potential for the development of HDL-based therapies highlighted. PMID- 26546992 TI - Adult Intramedullary Teratoma of the Spinal Cord: A Case Report and Review of Literature. AB - BACKGROUND: Teratomas of the spinal cord constitute 0.1% of all spinal tumors, and these lesions are extremely rare in adults. The authors describe a rare case of intradural intramedullary teratoma of the conus medullaris and perform review of literature of intramedullary teratomas seen in the thoracolumbar region. CASE DESCRIPTION: A 48-year-old man presented with fasciculations in the bilateral upper and lower extremities. Radiologic findings revealed an L2-L3 level intradural, nonenhancing, extramedullary cystic mass measuring 15 * 13 mm with a 6-mm enhancing nodule at the level of the conus medullaris. The patient was followed up for 1 year, during which time enlargement of the lesion with new areas of patchy contrast enhancement were observed. L1-L2 decompressive laminectomies were performed, and gross total resection of the lesion was achieved. Histopathologic examination confirmed the diagnosis of benign mature cystic teratoma. A literature review revealed no incidence difference in intramedullary teratomas between males and females (P > 0.05). The mean age at the time of diagnosis was 36.4 +/- 12.3 years for men and 41.3 +/- 11.6 for women (P < 0.05). The mean symptom duration before treatment was 64.6 +/- 79.4 months for females and 20.7 +/- 13.8 months for men (P < 0.05). Complete resection was achieved in 48.1% of the cases. CONCLUSIONS: Teratomas should be taken into consideration in the differential diagnosis of intramedullary lesions when the imaging reveals variable signal intensity because of tissue heterogeneity. A partial resection is a viable treatment option when the lesion is attached to vital structures because of the low recurrence rates reported in the literature. PMID- 26546993 TI - Ventriculoperitoneal Shunt Infection with Mycobacterium abscessus: A Rare Cause of Ventriculitis. AB - BACKGROUND: Mycobacterium abscessus is a rapidly growing atypical mycobacterium implicated in chronic lung disease, otitis media, surgical site infections, and disseminated cutaneous diseases. It is typically seen in patients with some degree of immunosuppression. Only 1 previous case has been reported in the setting of ventriculoperitoneal (VP) shunt infection. We report a case of M abscessus as the causative organism in a VP shunt infection in an immunocompetent adult. CASE DESCRIPTION: A 67-year-old woman required VP shunt placement after aneurysmal subarachnoid hemorrhage complicated by hydrocephalus. Her course was complicated by repeat hospitalization for 2 shunt infections, the second of which did not respond to standard antibiotic therapy. Cultures repeatedly grew M abscessus. The patient continued to decline and eventually died after transfer to the palliative care service. CONCLUSIONS: Nontuberculous mycobacteria are rare, atypical organisms in the setting of VP shunt infection. Patients with ventriculitis secondary to atypical mycobacteria may exhibit drug-resistant cerebrospinal fluid pleocytosis in the face of standard antibiotic regimens. PMID- 26546994 TI - Adjuvant Stereotactic Radiosurgery Reduces Need for Retreatments in Patients with Meningioma Residuals. AB - BACKGROUND: Radical surgical resection of cerebral meningiomas involving the dura mater of venous sinuses is challenging, and tumor residuals are frequently left after surgery. This study sought to evaluate the effect of adjuvant stereotactic radiosurgery (aSRS) on the time to significant growth of meningioma residuals requiring retreatment. METHODS: A total of 119 consecutive patients (2004-2013) receiving primary surgical treatment for a meningioma in proximity to a venous structure were included. The patients were assessed retrospectively, with a focus on retreatments and mortality. Radicality of initial tumor surgery was scored using postoperative magnetic resonance imaging. Three subgroups were identified: 1) radical total resection (RTR); 2) near-total resection (NTR), followed by aSRS (NTR + aSRS); and 3) NTR but no aSRS (NTR - aSRS). In the NTR - aSRS group, intervention was initiated after radiologic (magnetic resonance imaging) findings verified growth of residual tumor, in contrast to the NTR + aSRS group, which received aSRS before regrowth. Time to first retreatment, progression-free survival (PFS), and overall survival were analyzed with the log-rank test and multiple-events Cox regression. RESULTS: RTR was associated with the best prognosis. The patients in the NTR + aSRS group had significantly longer time to first retreatment compared with NTR - aSRS patients (P < 0.001). There was also a significant difference in mortality (P < 0.05) and a tendency to prolonged PFS (P = 0.07) in the NTR + aSRS group. The Cox regressions confirmed the positive effects of NTR + aSRS on time to retreatment (hazard ratio, 7.3; P < 0.01) and PFS (hazard ratio, 3.69; P = 0.055). CONCLUSIONS: aSRS of meningioma residuals had a positive effect on tumor control and should be considered in patients with meningioma residuals. PMID- 26546995 TI - The Vascular Notch Ligands Delta-Like Ligand 4 (DLL4) and Jagged1 (JAG1) Have Opposing Correlations with Microvascularization but a Uniform Prognostic Effect in Primary Glioblastoma: A Preliminary Study. AB - PURPOSE: Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. METHODS: Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). RESULTS: The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). CONCLUSIONS: DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma. PMID- 26546996 TI - Hospital-Acquired Infections after Aneurysmal Subarachnoid Hemorrhage: A Nationwide Analysis. AB - BACKGROUND: This is the first nationwide study to evaluate the factors associated with developing hospital-acquired infections (HAIs) after aneurysmal subarachnoid hemorrhage (SAH) and analyze their impact on the efficiency of hospital care. METHODS: Data from patients with SAH who underwent aneurysm repair were extracted from the Nationwide Inpatient Sample (2008-2011). Urinary tract infections, pneumonia, central venous catheter (CVC)-associated blood stream infection, and meningitis/ventriculitis were evaluated. Independent predictors of HAIs used in multivariable logistic regression modeling were chosen using forward selection; hierarchical multivariable linear regression assessed length of stay and charges. RESULTS: Seven thousand five hundred sixteen admissions were included. Independent predictors in the logistic regression for developing a urinary tract infection (23.9%) included older age, female sex, noninfectious complications (P < 0.001), intracerebral hemorrhage (P = 0.009), and diabetes with complications (P = 0.04). Pneumonia (23.0%) was associated with older age (P = 0.003), congestive heart failure, severity of SAH, and noninfectious complications (P < 0.001). Severity of SAH and noninfectious complications were predictors of meningitis/ventriculitis (4.4%; P <= 0.02), whereas intracerebral hemorrhage and noninfectious complications were predictors of CVC-associated infections (1.0%; P <= 0.02). All HAIs were associated with significantly longer hospitalizations and higher charges. Pneumonia (odds ratio [OR], 2.85; 95% confidence interval (CI), 2.44-3.34) and CVC-associated infections (OR, 2.42; 95% CI, 1.26-4.66) were also independently associated with greater odds of poor outcome (death or institutional care). CONCLUSION: In this nationwide analysis, urinary tract infections and pneumonia were the most common hospital-acquired infections after SAH. Although all infections were associated with significantly longer hospitalizations and greater charges, pneumonia and CVC-associated infections were also associated with increased likelihood of a poor outcome. PMID- 26546997 TI - An Increased Serum Level of Lipoprotein(a) Is a Predictor for Deep Vein Thrombosis in Patients with Spinal Cord Injuries. AB - OBJECTIVE: This prospective cohort-designed study was performed to verify whether higher levels of serum lipoprotein(a) (Lp(a)) could be a risk factor for deep vein thrombosis (DVT) in Chinese patients with spinal cord injuries (SCI). METHODS: During 2013-2014, consecutive patients with first-ever SCI were recruited and assessed for DVT using color Doppler ultrasonography for 15 days after injury and whenever clinically requested. Using logistic regression models, multivariate analyses were performed. Receiver operating characteristic curves tested the overall predicted accuracy of Lp(a) and other markers. RESULTS: In this study, 358 patients were screened in the analysis, and 279 patients with SCI were included and completed the 15-day follow-up. Fifty-five patients (19.7%) were diagnosed with DVT. Patients with SCI with DVT had significantly higher Lp(a) levels on admission (554 mg/L [interquartile range, 416-790 mg/L] vs. 158 mg/L [interquartile range, 72-252 mg/L]; P < 0.0001). Adjusted for common risk factors, multivariate analyses showed that serum Lp(a) >= 300 mg/L could be used independently to predict DVT (odds ratio, 10.35; 95% confidence interval [CI], 2.37-45.35; P < 0.0001). With an area under the curve (AUC) of 0.91 (95% CI, 0.86 0.94), Lp(a) showed a significantly greater discriminatory ability in predicting DVT compared with high-sensitivity C-reactive protein (AUC, 0.81; 95% CI, 0.74 0.88; P < 0.01), homocysteine (AUC, 0.78; 95% CI, 0.71-0.84; P < 0.01) and age (AUC, 0.66; 95% CI, 0.59-0.73; P < 0.001). CONCLUSIONS: Increased serum Lp(a) levels were independent predictors of DVT in patients with SCI in China, suggesting a possible role of Lp(a) in the pathogenesis of DVT. PMID- 26546998 TI - Survey of the Effectiveness of Internet Information on Patient Education for Bone Morphogenetic Protein. AB - OBJECTIVE: In light of recent reports of potential short- and long-term complications of bone morphogenetic protein (BMP) and increasing "off-label" use among spine surgeons, we wished to analyze online information on BMP and its controversial uses, as patients frequently search the Internet for medical information, even though the quality and accuracy of available information are highly variable. METHODS: Between December 2014 and January 2015, we conducted a Google search to identify the 50 most accessed websites providing BMP information using the search phrase "bone morphogenetic protein." Websites were classified based on authorship. Each website was examined for the provision of appropriate patient inclusion and exclusion criteria, surgical and nonsurgical treatment alternatives, purported benefits, disclosure of common and potential complications, peer-reviewed literature citations, and discussion of off-label use. RESULTS: Two percent of websites were authored by private medical groups, 2% by academic medical groups, 10% by insurance companies, 16% by biomedical industries, 4% by news sources, 0% by lawyers, and 66% by others. Sixty-two percent referenced peer-reviewed literature. Benefits and complications were reported in 44% and 26% of websites, respectively. Surgical and nonsurgical treatment alternatives were mentioned in 16% and 4% of websites, respectively. Discussion of off-label BMP use occurred in 18% of websites. CONCLUSIONS: Our study showed the ineffectiveness of the Internet in reporting quality information on BMP use. We found that websites authored by insurance companies provide an acceptable foundation for patient education. This, however, cannot replace the need for a thorough dialogue between doctor and patient about risks, benefits, and indications. PMID- 26547000 TI - The Effect of Age, Sex, and Lesion Location on Initial Presentation in Patients with Brain Arteriovenous Malformations. AB - OBJECTIVE: To identify whether age, sex, and lesion location are associated with initial presentation in patients with brain arteriovenous malformations (AVMs). METHODS: Collected data of 3299 consecutive patients with AVM treated at Beijing Tiantan Hosptial from January 1980 to January 2015 were analyzed. The variables assessed were age at diagnosis, sex, AVM location, and mode of initial presentation. RESULTS: Initial presentation was AVM hemorrhage in 57.9%, seizure in 20.9%, chronic headache in 14.9%, focal neurologic deficit in 5.2%, and incidental in 1.2%. Younger age and female sex were associated with initial hemorrhage (all P < 0.05). Hemorrhage was more likely to occur in patients with AVMs in the basal ganglia, the corpus callosum, the ventricles, the cerebellum, and the brainstem (all P < 0.05). Male sex was associated with initial seizure (P < 0.05). Initial seizure was more likely to occur in patients with AVMs in the frontal, temporal, parietal, frontotemporal, and frontoparietal lobe (all P < 0.05). Compared with frontal AVMs, temporal AVMs were more likely to present with hemorrhage (P < 0.05) and less likely to present with seizure (P < 0.05). AVMs involving the occipital lobe were more likely to present with chronic headaches (P < 0.05). CONCLUSIONS: Initial AVM presentation varied with patient age, sex, and AVM locations. Younger age, female sex, and deep and infratentorial locations may be associated with initial hemorrhage. Male sex and frontal, temporal, and parietal AVM locations may be predictors of initial seizure. Chronic headache was more likely to occur in patients with AVMs involving the occipital lobe. PMID- 26546999 TI - Impact of Increasing Age on Outcomes of Spinal Fusion in Adult Idiopathic Scoliosis. AB - OBJECTIVE: To investigate the role of advancing age on postoperative complications and revision surgery after fusion for scoliosis. METHODS: A retrospective, cohort study was performed using the Thomson Reuters MarketScan database, examining patients with adult scoliosis who underwent spinal fusion from 2000 to 2009. Primary outcomes included infection, hemorrhage and pulmonary embolism (PE) within 90 days of surgery, and refusion. The effect of increasing age was estimated using the odds ratio (OR) of complications in a multivariate logistic regression analysis, and a Cox proportional hazard model estimated the hazard ratio of refusion. RESULTS: A total of 8432 patients were included in this study. Overall, the average age was 53.3 years, with 26.90% males and 39% with a Charlson Comorbidity Score of >= 1. Most patients had commercial insurance (66.81%), with 26.03% and 7.16% covered by Medicare and Medicaid, respectively. Increasing age (per 5-year increment) was a significant predictor of hemorrhagic complication (OR, 1.06; confidence interval [CI], 1.01-1.11; P = 0.0196), PE (OR, 1.09; CI, 1.03-1.16; P = 0.0031), infection (OR, 1.04; CI, 1.01-1.07; P = 0.0053), and refusion (hazard ratio, 1.07; CI, 1.02-1.13; P = 0.0103). CONCLUSIONS: In this study, age was associated with increased risk of hemorrhage, PE, infection, and refusion. With the aging population, the role of patient age on postoperative healing and outcomes deserves deeper investigation after repair of adult idiopathic scoliosis. PMID- 26547001 TI - Cell Therapy for Intracranial Aneurysms: A Review. AB - One in five patients undergoing endovascular coiling (the current standard of care for treating intracranial aneurysms) experience a recurrence of the aneurysm as a result of improper healing. Recurrence remains the only major drawback of the coiling treatment and has been the focus of many studies over the last two decades. Cell therapy, a novel treatment modality in which therapeutic cells are introduced to the site of the injury to promote tissue regeneration, has opened up new possibilities for treating aneurysms. The healing response that ensues aneurysm embolization includes several cellular processes that can be targeted with cell therapy to prevent the aneurysm from recurring. Ten preclinical studies involving cell therapy to treat aneurysms were published between 1999 and 2014. In this review, we summarize the results of these studies and discuss advances, shortcomings, and the future of cell therapy for intracranial aneurysms. PMID- 26547002 TI - Microsurgical Approaches to the Ambient Cistern Region: An Anatomic and Qualitative Study. AB - OBJECTIVE: We used microscopy to conduct qualitative and quantitative analysis of 4 surgical approaches commonly used in the surgery of the ambient cistern: infratentorial supracerebellar (SC), occipital interhemispheric, subtemporal (ST), and transchoroidal (TC). In addition, we performed a parahippocampal gyrus resection in the ST context. METHODS: Each approach was performed in 3 cadaveric heads (6 sides). After the microscopic anatomic dissection, the parahippocampal gyrus was resected through an ST approach. The qualitative analysis was based on anatomic observation and the quantitative analysis was based on the linear exposure of vascular structures and the area of exposure of the ambient cistern region. RESULTS: The ST approach provided good exposure of the inferior portion of the cistern and of the proximal segments of the posterior cerebral artery. After the resection of the parahippocampal gyrus, the area of exposure improved in all components, especially the superior area. A TC approach provided the best exposure of the superior area compared with the other approaches. The posterolateral approaches (SC/occipital interhemispheric) to the ambient cistern region provided similar exposure of anatomic structures. There was a significant difference (P < 0.05) in linear exposure of the posterior cerebral artery when comparing the ST/TC and ST/SC approaches. CONCLUSIONS: This study has demonstrated that surgical approaches expose dissimilarly the different regions of the ambient cistern and an approach should be selected based on the specific need of anatomic exposure. PMID- 26547003 TI - Working with Plates in Spine Injuries. PMID- 26547004 TI - Variation in the h-Index and Its Use in the Assessment of Academic Output. PMID- 26547005 TI - Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury. AB - OBJECTIVE: Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. METHODS: Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale Extended (GOSE). RESULTS: Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score <= 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. CONCLUSIONS: GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities. PMID- 26547006 TI - Autophagy Inhibitor 3-MA Weakens Neuroprotective Effects of Posttraumatic Brain Injury Moderate Hypothermia. AB - OBJECTIVE: The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia. METHODS: Adult male Sprague Dawley rats were randomly divided into 3 groups (n = 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 MUL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 MUL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively. RESULTS: Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis. CONCLUSION: Our results suggest that the autophagy pathway is involved in the neuroprotective effect of post-TBI hypothermia and negative modulation of apoptosis may be 1 possible mechanism. PMID- 26547007 TI - Pharmacovigilance through the development of text mining and natural language processing techniques. PMID- 26547008 TI - Novel mycoviruses discovered from metatranscriptomics survey of soybean phyllosphere phytobiomes. AB - Mycoviruses can be beneficial to plants in that they can debilitate pathogenic fungi thereby reducing the severity of associated plant diseases. Studies to date have focused primarily on culturable fungi that represent a fraction of natural fungal populations. The nonculturable fungi, however, can harbor diverse populations of mycoviruses that reduce plant disease or enhance resistance to abiotic stress. Metatranscriptome analysis of field-grown plant samples using high-throughput sequencing offers the possibility of unbiased detection and quantification of mycoviruses regardless of the culturability of their fungal hosts together with the complete associated microbial consortia. In this study, we describe the fungal viromes of the phyllosphere of production soybean fields in Illinois, USA by analyzing the metatranscriptomes of thousands of soybean leaf samples collected during the 2008 and 2009 growing seasons. The analyses identified 25 partial genome sequences that represented at least 22 mycovirus genomes, only one of which had been described previously. The novel mycovirus genomes showed similarity to 10 distinct lineages including the genera Alphapartitivirus, Botybirnavirus, Endornavirus, Mitovirus, Mycoflexivirus, Ourmiavirus, Totivirus, Victorivirus, family Tombusviridae, order Mononegavirales, and the recently proposed genus Gemycircularvirus. The present study adds to the wealth of mycoviruses associated with plant phytobiomes and establishes groundwork needed for further characterization of the viruses. PMID- 26547009 TI - Immunoliposome-based immunomagnetic concentration and separation assay for rapid detection of Cronobacter sakazakii. AB - This study aimed to develop an immunoliposome-based immunomagnetic concentration and separation assay for the rapid detection of Cronobacter sakazakii (C. sakazakii), an acute opportunistic foodborne pathogenic bacterium, in both pure culture and infant formula. To develop the assay, magnetic nanoparticles (diameter 30 nm) were coated with immunoglobulin G (IgG), specifically anti-C. sakazakii IgG, and applied for the sensitive and efficient detection of C. sakazakii using immunoliposomes. The binding efficiency of anti-C. sakazakii IgG to the magnetic nanoparticles was 86.23 +/- 0.59%. The assay developed in this study detected as few as 3.3 * 10(3) CFUmL(-1) of C. sakazakii in pure culture within 2h 30 min; in comparison, an indirect non-competitive enzyme-linked immunosorbent assay was able to detect 6.2 * 10(5) CFUmL(-1) of C. sakazakii in pure culture after 17 h. The developed assay did not show any cross-reactivity with other Cronobacter spp. or pathogens belonging to other genera. In addition, the method was able to detect 10(3) CFUmL(-1) of C. sakazakii in infant formula without any pre-incubation. These results confirm that the immunoliposome-based immunomagnetic concentration and separation assay may facilitate highly sensitive, efficient, and rapid detection of C. sakazakii. PMID- 26547010 TI - Enzyme-free detection of sequence-specific microRNAs based on nanoparticle assisted signal amplification strategy. AB - Developing direct and convenient methods for microRNAs (miRNAs) analysis is of great significance in understanding biological functions of miRNAs, and early diagnosis of cancers. We have developed a rapid, enzyme-free method for miRNA detection based on nanoparticle-assisted signal amplification coupling fluorescent metal nanoclusters as signal output. The proposed method involves two processes: target miRNA-mediated nanoparticle capture, which consists of magnetic microparticle (MMP) probe and CuO nanoparticle (NP) probe, and nanoparticle mediated amplification for signal generation, which consists of fluorescent DNA Cu/Ag nanocluster (NC) and 3-mercaptopropionic acid (MPA). In the presence of target miRNA, MMP probe and NP probe sandwich-capture the target miRNA via their respective complementary sequence. The resultant sandwich complex (MMP probe miRNA-CuO NP probe) is separated using a magnetic field and further dissolved by acidolysis to turn CuO NP into a great amount of copper (II) ions (Cu(2+)). Cu(2+) could disrupt the interactions between thiol moiety of MPA and the fluorescent Cu/Ag NCs by preferentially reacting with MPA to form a disulfide compound as intermediate. By this way, the fluorescence emission of the DNA-Cu/Ag NCs in the presence of MPA increases upon the increasing concentration of Cu(2+), which is directly proportional to the amount of target miRNA. The proposed method allows quantitative detection of a liver-specific miR-221-5p in the range of 5 pM to 1000 pM with a detection limit of ~0.73 pM, and shows a good ability to discriminate single-base difference. Moreover, the detection assay can be applied to detect miRNA in cancerous cell lysates in excellent agreement with that from a commercial miRNA detection kit. PMID- 26547011 TI - Sodium Nitroprusside in Patients With Mixed Pulmonary Hypertension and Left Heart Disease: Hemodynamic Predictors of Response and Prognostic Implications. AB - BACKGROUND: Mixed pulmonary hypertension (PH) in heart failure (HF) is defined by transpulmonary gradient >= 12 and/or pulmonary vascular resistance (PVR) >= 240 dyne/s/cm(-5), but diastolic pressure gradient (DPG) >= 7 mmHg has been proposed more recently. We evaluated the acute hemodynamic response to sodium nitroprusside (SNP) specifically in relation to the proposed DPG criterion >=7 mmHg and the prognostic significance of response to SNP in patients with mixed PH and advanced HF. METHODS: Ninety-eight consecutive patients with advanced HF and mixed PH underwent cardiac catheterization and acute SNP infusion. Baseline hemodynamic parameters included transpulmonary gradient, PVR, DPG, and pulmonary capacitance (PCap). Hemodynamic response to SNP was defined as a reduction in PVR of at least 20%. The composite endpoint was death/heart transplantation/mechanical circulatory support. RESULTS: Sixty of the 98 patients were SNP responders. SNP resulted in significant reductions in filling pressures and PVR and increase in stroke volume and PCap. DPG (not baseline PVR) was significantly associated with hemodynamic response to SNP on logistic regression analysis. The sensitivity and specificity of a DPG >=7 mmHg to identify nonresponders to SNP were 74% and 97%, respectively. At median follow-up of 218 (148-324) days, 13 and 19 patients of the SNP responders and nonresponders, respectively, met the composite endpoint (P = .021 by log-rank test). Hemodynamic response to SNP and PCap were independently associated with the composite outcome of survival free from transplantation/mechanical circulatory support. CONCLUSION: Baseline DPG >= 7 mmHg is associated with poor PVR response to SNP. PVR response to SNP and PCap are associated with a more favorable prognosis in patients with advanced HF and mixed PH. PMID- 26547012 TI - Impact of Annual Hospital Volume on Outcomes after Left Ventricular Assist Device (LVAD) Implantation in the Contemporary Era. AB - INTRODUCTION: There are few data in the literature regarding impact of annual hospital volume on outcomes such as mortality and length of stay (LOS) post-LVAD implantation. METHODS: We queried the nationwide inpatient sample from 2008 to 2011 using International Classification of Diseases, 9th Revision procedure code 37.66. We included patients >=18 years without primary diagnosis of orthotopic heart transplant. Annual volume of LVAD implantation was computed for each hospital. Multivariable hierarchical mixed effect logistic regression models were used to determine predictors of in-hospital mortality and LOS. RESULTS: There were 1749 LVAD implants from 2008 to 2011; patients had a mean age of 55.4 years, and 23% were female. In-hospital mortality decreased from 20.9% in the first tertile (1-22 LVADs/y) to 13.7% in the third tertile (>=35 LVADs/y) of hospital volume. Median LOS decreased from 34 days in the first tertile to 28 days in third tertile of hospital volume. The adjusted odds ratios of the highest tertile of hospital volume in predicting in-hospital mortality and LOS were 0.41 (0.26 0.64, P < .001) and 0.41 (0.23-0.73, P = .003), respectively. Restricted cubic spline analysis showed that a volume threshold of >20 LVADs/year was associated with favorable mortality rates of <10%. CONCLUSIONS: High annual LVAD volume is associated with significantly decreased in-hospital mortality and LOS after LVAD implantation. Center experience is an important determinant of optimal patient outcomes. PMID- 26547013 TI - The Prevalence of Stages of Heart Failure in Primary Care: A Population-Based Study. AB - BACKGROUND: Planning strategies to prevent heart failure (HF) in developing countries require epidemiologic data in primary care. The purpose of this study was to estimate the prevalence of HF stages and their phenotypes, HF with preserved ejection fraction (HFPEF), and HF with reduced EF (HFREF) and to determine B-type natriuretic peptide (BNP) levels to identify HF in the adult population. METHODS AND RESULTS: This is a cross-sectional study including 633 individuals, aged >=45 years, who were randomly selected and registered in a primary care program of a medium-sized city in Brazil. All participants were underwent clinical evaluations, BNP measurements, electrocardiograms, and tissue Doppler echocardiography in a single day. The participants were classified as stage 0 (healthy, 11.7%), stage A (risk factors, 36.6%), stage B (structural abnormalities, 42.7%), or stage C (symptomatic HF, 9.3%). Among patients with HF, 59% presented with HFPEF and 41% presented with HFREF. The mean BNP levels were 20 pg/mL(-1) in stage 0, 20 pg/mL(-1) in stage A, 24 pg/mL(-1) in stage B, 93 pg/mL(-1) in HFPEF, and 266 pg/mL(-1) in HFREF. The cutoff BNP level with optimal sensitivity (92%) and specificity (91%) to identify HF was 42 pg/mL(-1). CONCLUSION: The present study demonstrated a high prevalence of individuals at risk for HF and the predominance of HFPEF in a primary care setting. The clinical examination, along with BNP and tissue Doppler echocardiography, may facilitate early detection of stages A and B HF and allow implementation of interventions aimed at preventing progression to symptomatic HF. PMID- 26547014 TI - Longitudinal Changes in Familiarity, Free and Cued Odor Identification, and Edibility Judgments for Odors in Aging Individuals. AB - This longitudinal study investigated changes in olfaction as assessed by a set of tasks requiring different aspects of semantic information in normal aging individuals. Using 16 odorous items from a standardized olfactory test, the Scandinavian Odor Identification Test, 107 middle aged and older adults were assessed up to three times over a period of 6.5 years, requesting them to rate familiarity and edibility for each odorous item before identifying it with or without presenting verbal cues. Using linear mixed models, the longitudinal analyses revealed significant correlations between all olfactory measures. Furthermore, we found an almost parallel age-related decline in all olfactory tasks, although free identification performance indicated a trend toward faster decline with age. Women showed less decline compared with men, in particular for edibility judgments. The results corroborate earlier cross-sectional findings showing significant correlations between the olfactory tasks. In the present study of healthy middle-aged and older adults, we found a parallel longitudinal decline across different tests of olfaction. PMID- 26547015 TI - A Scent of Anxiety: Olfactory Context Conditioning and its Influence on Social Cues. AB - Perception and evaluation of objects are highly dependent on surrounding contexts. Threatening contexts enhance processing of faces. Because odors are assumed to deliver strong contextual information, the present study aimed at demonstrating 1) that odors can constitute threat and safety contexts, and 2) consequently modulate the processing of faces presented in these contexts. Therefore, previously neutral odors were used as contextual stimuli in a context conditioning paradigm, resulting in an olfactory anxiety and a safety context. Then, faces showing angry, neutral, or fearful expressions were presented within both contexts during a test phase to investigate the effects of threat versus safety contexts on face perception. The late positive potential (LPP) from the EEG, skin conductance level, and subjective ratings were recorded. Results reveal successful olfactory context conditioning as reflected in enhanced processing of the anxiety context, indicated by enhanced LPP after conditioning, increased skin conductance level, and marginally respectively increased ratings. Moreover, faces presented within the threat context were rated as more unpleasant and marginally more arousing than faces presented in the safety context. Thus, olfactory stimuli can serve as context in fear conditioning, and a threatening olfactory context seems to enhance processing of stimuli perceived within this context. PMID- 26547016 TI - Dynamic nuclear polarization in solid samples by electrical-discharge-induced radicals. AB - Dynamic nuclear polarization (DNP) is a method for enhancing nuclear magnetic resonance (NMR) signals that has many potential applications in chemistry and medicine. Traditionally, DNP signal enhancement is achieved through the use of exogenous radicals mixed in a solution with the molecules of interest. Here we show that proton DNP signal enhancements can be obtained for solid samples without the use of solvent and exogenous radicals. Radicals are generated primarily on the surface of a solid sample using electrical discharges. These radicals are found suitable for DNP. They are stable under moderate vacuum conditions, yet readily annihilate upon compound dissolution or air exposure. This feature makes them attractive for use in medical applications, where the current variety of radicals used for DNP faces regulatory problems. In addition, this solvent-free method may be found useful for analytical NMR of solid samples which cannot tolerate solvents, such as certain pharmaceutical products. PMID- 26547017 TI - Th17 master transcription factors RORalpha and RORgamma regulate the expression of IL-17C, IL-17D and IL-17F in Cynoglossus semilaevis. AB - The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors. In this study, we examined the regulatory properties of RORalpha (CsRORalpha) and RORgamma (CsRORgamma) in tongue sole (Cynoglossus semilaevis). CsRORalpha and CsRORgamma expression was detected in major lymphoid organs and altered to significant extents after bacterial and viral infection. CsRORalpha enhanced the activities of CsIL-17C, CsIL-17D, and CsIL-17F promoters, which contain CsRORalpha and CsRORgamma binding sites. CsRORgamma also upregulated the promoter activities of CsIL-17D and CsIL 17F but not CsIL-17C. CsRORalpha and CsRORgamma proteins were detected in the nucleus, and overexpression of CsRORalpha in tongue sole significantly increased the expression of CsIL-17C, CsIL-17D, and CsIL-17F, whereas overexpression of CsRORgamma significantly increased the expression of CsIL-17C and CsIL-17F but no CsIL-17D. These results indicate that RORalpha and RORgamma in teleost regulate the expression of IL-17 members in different manners. PMID- 26547018 TI - Pedestrian injury risk and the effect of age. AB - Older adults and pedestrians both represent especially vulnerable groups in traffic. In the literature, hazards are usually described by the corresponding injury risks of a collision. This paper investigates the MAIS3+F risk (the risk of sustaining at least one injury of AIS 3 severity or higher, or fatal injury) for pedestrians in full-frontal pedestrian-to-passenger car collisions. Using some assumptions, a model-based approach to injury risk, allowing for the specification of individual injury risk parameters for individuals, is presented. To balance model accuracy and sample size, the GIDAS (German In-depth Accident Study) data set is divided into three age groups; children (0-14); adults (15 60); and older adults (older than 60). For each group, individual risk curves are computed. Afterwards, the curves are re-aggregated to the overall risk function. The derived model addresses the influence of age on the outcome of pedestrian-to car accidents. The results show that older people compared with younger people have a higher MAIS3+F injury risk at all collision speeds. The injury risk for children behaves surprisingly. Compared to other age groups, their MAIS3+F injury risk is lower at lower collision speeds, but substantially higher once a threshold has been exceeded. The resulting injury risk curve obtained by re aggregation looks surprisingly similar to the frequently used logistic regression function computed for the overall injury risk. However, for homogenous subgroups such as the three age groups - logistic regression describes the typical risk behavior less accurately than the introduced model-based approach. Since the effect of demographic change on traffic safety is greater nowadays, there is a need to incorporate age into established models. Thus far, this is one of the first studies incorporating traffic participant age to an explicit risk function. The presented approach can be especially useful for the modeling and prediction of risks, and for the evaluation of advanced driver assistance systems. PMID- 26547019 TI - Wang et al. Arch. Oral. Biol. (2015) 60: 385-392. PMID- 26547020 TI - Amazonian delicacy tucupi is as erosive as a cola-based soft drink. AB - OBJECTIVE: Acidic diets are advocated as main risk factor for tooth erosion, which could be prevented, or at least controlled, if patients were early advised. It is important to identify, hence, if possible dietary constituents regionally consumed on large scale, such as tucupi, a low-pH yellowish-green color and strong flavor delicacy made from the juice of a bitter cassava, may explain its occurrence in specific patient groups. This cross-over in situ/ex vivo study evaluated tucupi's ability to promote erosion of bovine enamel by assessing its percentage of surface microhardness change (%SMHC), taking a cola-based soft drink and human saliva as positive and negative controls. DESIGN: For three 7 days spaced out legs of 7 days each, nine volunteers wore palatal devices with three bovine enamel blocks, which were challenged with one of the following solutions: TUC-tucupi (n=27); COL-cola-based soft drink (n=27); SAL-saliva (n=27). Erosive challenges were performed extra-orally (4*/day) by dropping TUC or COL at room temperature on specimens. After 5min, palatal devices were replaced into the mouth. SAL permanently acted as the negative control while volunteers solely wore the device. One-way ANOVA followed by Tukey's post-hoc tests (alpha=0.05) were applied. RESULTS: TUC promoted an enamel %SMHC (-21.56+/ 10.08(a)) similar than that promoted by COL (-18.19+/-12.99(a); p=0.275), which were both significantly higher than that promoted by SAL (-1.86+/-13.65(b); p<0.0001). CONCLUSIONS: Besides the most worldwide appreciated cola-based soft drink, the greatly consumed Amazonian delicacy tucupi can be considered a potential risk factor for tooth erosion. PMID- 26547021 TI - Cross-modal influence on oral size perception. AB - OBJECTIVE: Evidence suggests people experience an oral size illusion and commonly perceive oral size inaccurately; however, the nature of the illusion remains unclear. The objectives of the present study were to confirm the presence of an oral size illusion, determine the magnitude (amount) and direction (underestimation or overestimation) of the illusion, and determine whether immediately prior cross-modal perceptual experiences affected the magnitude and direction. DESIGN: Participants (N=27) orally assessed 9 sizes of stainless steel spheres (1/16 in to 1/2 in) categorized as small, medium, or big, and matched them with digital and visual reference sets. Each participant completed 20 matching tasks in 3 assessments. For control assessments, 6 oral spheres were matched with reference sets of same-sized spheres. For primer-control assessments, similar to control, 6 matching tasks were preceded by cross-modal experiences of the same-sized sphere. For experimental assessments, 8 matching tasks were preceded by a cross-modal experience of a differently sized sphere. RESULTS: For control assessments, small and medium spheres were consistently underestimated, and big spheres were consistently overestimated. For experimental assessments, magnitude and direction of the oral size illusion varied according to the size of the sphere used in the cross-modal experience. CONCLUSION: Results seemed to confirm an oral size illusion, but direction of the illusion depended on the size of the object. Immediately prior cross-modal experiences influenced magnitude and direction of the illusion, suggesting that aspects of oral perceptual experience are dependent upon factors outside of oral perceptual anatomy and the properties of the oral stimulus. PMID- 26547022 TI - Mad honey intoxication: A systematic review on the 1199 cases. AB - Mad honey, produced by honeybees from the nectars of Rhododendron genus (R. ponticum and R. luteum) flowers, is widely used in indigenous medicine, especially in the treatment of hypertension and sexual dysfunction. However, the consumption of this honey can result in intoxication soon after. The diagnosis of honey poisoning and a full understanding of its treatment is important for both effective and immediate treatment, and also for the prevention of unnecessary costs. Upon the evaluation of approximately 34 years of case reports between 1981 and 2014, it was found that the cases of poisoning were more frequently reported in males (75.17%) and between the ages 41 to 65. The most common complaints related to honey poisoning were dizziness, nausea, presyncope and the ECG findings were: sinus bradycardia (79.58%), complete atrioventricular block (45.83%), atrioventricular block (30.91%), ST-segment elevation (22.63%), and nodal rhythm (11.27%), As a result of the evaluation of 1199 cases, it was found that no deaths were reported. The patients were most frequently treated with 0.5 mg atropine (37.79%), 1 mg atropine (49.73%), salin (iv fluid) (65.35%), and generally the patients were discharged within 24 h after recovery. PMID- 26547023 TI - The use of ephyrae of a scyphozoan jellyfish, Aurelia aurita, in the aquatic toxicological assessment of Macondo oils from the Deepwater Horizon incident. AB - Ephyrae of the scyphozoan jellyfish, Aurelia aurita, were evaluated in 96-hr acute toxicity tests for lethal response to Macondo crude oils from the Deepwater Horizon (DWH) incident in the Gulf of Mexico (GOM), Corexit 9500, and oil dispersant mixtures. Water accommodated fractions (WAFs) of weathered and unweathered Macondo crude oils were not acutely toxic to ephyrae (LC50s > 100% WAF). The total PAHs (TPAHs), measured as the sum of 46 PAHs, averaged 21.1and 152 ug TPAH/L for WAFs of weathered and unweathered oil, respectively. Mortality was significantly (p = <0.0001) higher in the three highest exposure concentrations (184-736 ug TPAH/L) of chemically dispersed WAFs (CEWAF) compared to controls. Dispersant only tests resulted in a mean LC50 of 32.3 uL/L, which is in the range of previously published LC50s for marine zooplankton. Changes in appearance and muscle contractions were observed in organisms exposed to CEWAF dilutions of 12.5 and 25%, as early as 24 h post-exposure. Based on the results of these tests, crude oil alone did not cause significant acute toxicity; however, the presence of chemical dispersant resulted in substantial mortality and physical and behavioral abnormalities either due to an increase in hydrocarbons or droplet exposure. PMID- 26547024 TI - Cytotoxic and genotoxic profiles of benzo[a]pyrene and N-nitrosodimethylamine demonstrated using DNA repair deficient DT40 cells with metabolic activation. AB - Benzo[a]pyrene and N-nitrosodimethylamine are major genotoxic compounds present in cigarette smoke, food and oil. To examine the type(s) of DNA damage induced by these compounds, we used a panel of DNA-repair-pathway-deficient mutants generated from chicken DT40 cells and achieved metabolic activation of the test compounds by including rat liver S9 mix. Consistent with expections, benzo[a]pyrene and N-nitrosodimethylamine require metabolicactivation to become genotoxic. The REV3(-/-) mutant cell line exhibited the highest sensitivity, in terms of increased cytotoxicity, to the both compounds after metabolic activation consistent with the known ability of these two compounds to induce DNA adducts. Strikingly, we found that the RAD54(-/-)/KU70(-/-) cell line, a mutant defective in the repair of double-strand breaks, is sensitive to benzo[a]pyrene, suggesting that this compound also induces strand breaks in these cells. In this study we combined a previously employed method, metabolic activation by S9 mix, with the use of a DNA-repair mutant panel, thereby broadening the range of compounds that can be screened for potential genotoxicity. PMID- 26547025 TI - Human CYP2E1-dependent mutagenicity of mono- and dichlorobiphenyls in Chinese hamster (V79)-derived cells. AB - Polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants with confirmed carcinogenicity to humans. Metabolic activation of lower chlorinated PCBs to genotoxic metabolites may involve hydroxylation and further oxidation, and some hydroxylated metabolites may be sulfo-conjugated. However, the genotoxicity of individual PCB compounds is largely unknown. In this study, 15 mono- and dichlorobiphenyls were investigated for genotoxicity using the micronucleus and Hprt mutagenicity assays in a Chinese hamster V79-derived cell line expressing both human cytochrome P450 (CYP) 2E1 and human sulfotransferase (SULT) 1A1 (V79-hCYP2E1-hSULT1A1). All tested compounds were inactive in both assays in V79 control cells. However, eight dichlorobiphenyls strongly induced micronuclei and other congeners were weakly positive for this endpoint in V79 hCYP2E1-hSULT1A1 cells. The effects of each PCB in V79-hCYP2E1-hSULT1A1 cells were abolished or reduced in the presence of a CYP2E1 inhibitor (1 aminobenzotriazole), or enhanced by pretreatment of the cells with (CYP2E1 inducing) ethanol, while the genotoxicity was not significantly affected by a SULT1 inhibitor (pentachlorophenol). As representative dichlorobiphenyls, PCB 5, 10, 8 and 11 (2,3-, 2,5-, 2,4'- and 3,3'-dichlorobiphenyl, respectively) strongly induced Hprt gene mutations in V79-hCYP2E1-hSULT1A1 cells in a concentration dependent manner. This is the first indication that human CYP2E1 is capable of converting a series of dichlorobiphenyls to strong mutagens. PMID- 26547026 TI - Kinetic analysis of the hydrolysis of methyl parathion using citrate-stabilized 10 nm gold nanoparticles. AB - "Ligand-free" citrate-stabilized 10 nm gold nanoparticles (AuNPs) promote the hydrolysis of the thiophosphate ester methyl parathion (MeP) on the surface of gold as a function of pH and two temperature values. At 50 degrees C, the active surface gold atoms show catalytic turnover ~4 times after 8 h and little turnover of gold surface atoms at 25 degrees C with only 40% of the total atoms being active. From Michaelis-Menten analysis, k(cat) increases between pH 8 and 9 and decreases above pH 9. A global analysis of the spectral changes confirmed the stoichiometric reaction at 25 degrees C and the catalytic reaction at 50 degrees C and mass spectrometry confirmed the identity of p-nitrophenolate (PNP) product. Additional decomposition pathways involving oxidation and hydrolysis independent of the formation of PNP were also seen at 50 degrees C for both catalyzed and un-catalyzed reactions. This work represents the first kinetic analysis of ligand-free AuNP catalyzed hydrolysis of a thiophosphate ester. PMID- 26547027 TI - Effects of tris (2-butoxyethyl) phosphate (TBOEP) on endocrine axes during development of early life stages of zebrafish (Danio rerio). AB - Due to phasing out of additive flame retardants such as polybrominated diphenyl ethers (PBDEs), Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute. TBOEP is ubiquitous in the environment and has been measured at concentrations of micrograms per liter (MUg L(-1)) in surface waters and wastewater. Information on potential adverse effects on development of aquatic organisms caused by exposure to environmentally relevant concentrations of TBOEP is limited, especially for effects that may be caused through impairment of endocrine-modulated homeostasis. Therefore, this study was conducted to determine effects of TBOEP on ontogeny and transcription profiles of genes along the hypothalamus-pituitary-thyroidal (HPT), hypothalamus-pituitary-adrenal (HPA), and hypothalamus-pituitary-gonadal (HPG) axes in embryos/larvae of zebrafish (Danio rerio). Exposure to TBOEP (2-5,000 MUg L(-1)) from 3 h post-fertilization (hpf) to 120 hpf induced developmental malformations in zebrafish with a LC50 of 288.54 MUg L(-1) at both 96 hpf and 120 hpf. The predicted no observed effect concentration (PNOEC) was 2.40 MUg L(-1). Exposure to 2, 20, or 200 MUg TBOEP L( 1) altered expression of genes involved in three major molecular pathways in a concentration-dependent manner after 120 hpf. TBOEP caused lesser expression of some genes involved in synthesis of hormones, such as (pomc and fshbeta) as well as upregulating expression of some genes coding for receptors (thr, tshr, gr, mr, er and ar) in zebrafish larvae. These changes at the molecular level could result in alterations of endocrine function, which could result in edema or deformity and ultimately death. PMID- 26547028 TI - Determination of natural radioactivity in irrigation water of drilled wells in northwestern Saudi Arabia. AB - The levels of natural radiation in bedrock groundwater extracted from drilled wells in selected farms in the northwestern part of Saudi Arabia were addressed. The investigated waters form a source of irrigation for vegetables, agricultural crops, wheat, and alfalfa to feed livestock consumed by the general public. Information about water radioactivity in this area is not available yet. Therefore, this study strives to contribute to the quality assessment of the groundwater of these wells that are drilled into the non-renewable Saq sandstone aquifer. Hence, gross alpha and beta activities as well as the concentrations of (224)Ra, (226)Ra, (228)Ra, (234)U, (238)U, and U(total) were measured, compared to national and international limits and contrasted with data quoted from the literature. Correlations between the activities of the analyzed radionuclides were discussed. The concentrations of gross alpha and beta activities as well as (228)Ra were identified by liquid scintillation counting whereas alpha spectrometry was used to determine (224)Ra, (226)Ra, (234)U and (238)U after separation from the matrix by extraction chromatography. The mean activity concentrations of gross alpha and beta were 3.15 +/- 0.26 Bq L(-1) and 5.39 +/- 0.44 Bq L(-1), respectively. Radium isotopes ((228)Ra and (226)Ra) showed mean concentrations of 3.16 +/- 0.17 Bq L(-1) and 1.12 +/- 0.07 Bq L(-1), respectively, whereas lower levels of uranium isotopes ((234)U and (238)U) were obtained. PMID- 26547029 TI - Arsenic uptake, arsenite efflux and plant growth in hyperaccumulator Pteris vittata: Role of arsenic-resistant bacteria. AB - Bacteria-mediated arsenic (As) transformation and their impacts on As and P uptake and plant growth in As-hyperaccumulator Pteris vittata (PV) were investigated under sterile condition. All As-resistant bacteria (9 endophytic and 6 rhizospheric) were As-reducers except one As-oxidizer. After growing two months in media with 37.5 mg kg(-1) AsV, As concentrations in the fronds and roots were 3655-5389 (89-91% AsIII) and 971-1467 mg kg(-1) (41-73% AsIII), corresponding to 22-52% decrease in the As in the media. Bacterial inoculation enhanced As and P uptake by up to 47 and 69%, and PV growth by 20-74%, which may be related to elevated As and P in plants (r = 0.88-0.97, p < 0.05). Though AsV was supplied, 95% of the As in the bacteria-free media was AsIII, suggesting efficient efflux of AsIII by PV roots (120 ug g(-1) root fw). This was supported by the fact that no AsV was detected in media inoculated with As-reducers while 95% of AsV was detected with As-oxidizer. Our data showed that, under As-stress, PV reduced As toxicity by efficient AsIII efflux into media and AsIII translocation to the fronds, and bacteria benefited PV growth probably via enhanced As and P uptake. PMID- 26547030 TI - Polychlorinated biphenyl congeners in sediment cores from the Upper Mississippi River. AB - We determined polychlorinated biphenyls (PCBs) and radionuclide (137)Cs in sediment cores from the Upper Mississippi River (UMR) and the Iowa River, Iowa, at their confluence. Vertical distribution of (137)Cs indicated negligible mixing in the UMR core, while the Iowa River core showed signs of mixing. A clear (137)Cs peak was found in the UMR core, which was correlated to 1963. The PCB vertical distribution in UMR core was similar to the historical trend in Aroclor production observed in Great Lakes cores, with a peak close to the (137)Cs peak, suggesting a date near 1960. In general, PCB congener profiles in both cores resembled the Iowa soil background signal. We concluded that despite evidence of mixing in the Iowa River core, both cores retain the PCB signature of historical and regional environmental exposure. Further, our results indicate that this iconic waterway has a long history of PCBs that reflects national production and use. PMID- 26547031 TI - Modeling the adsorption of PAH mixture in silica nanopores by molecular dynamic simulation combined with machine learning. AB - The persistence of polycyclic aromatic hydrocarbons (PAHs) in contaminated soils is largely controlled by their molecular fate in soil pores. The adsorption and diffusion of 16 PAHs mixture in silica nanopore with diameter of 2.0, 2.5, 3.0 and 3.5 nm, respectively, were characterized by adsorption energy, mean square displacement, free surface area and free volume fraction using molecular dynamic (MD) simulation. Results suggested that PAHs adsorption in silica nanopores was associated with diffusion process while competitive sorption was not the dominant mechanism in context of this study. The partial least squares (PLS) regression and machine learning (ML) methods (i.e. support vector regression, M5 decision tree and multilayer perceptrons) were used to correlate the adsorption energy with the pore diameter and PAH properties (number of carbon atoms, aromatic ring number, boiling point, molecular weight, octanol-water partition coefficient, octanol-organic carbon partition coefficient, solvent accessible area, solvent accessible volume and polarization). Results indicated that the PAH adsorption could not be predicted by linear regression as the R(2)Y and Q(2)Y coefficients of PLS analysis was 0.375 and 0.199, respectively. The nonlinearity was well recognized by ML with correlation coefficient up to 0.9. Overall, the combination of MD simulation and ML approaches can assist in interpreting the sequestration of organic contaminants in the soil nanopores. PMID- 26547032 TI - An assessment of the frequency of mutations in the GBA and VPS35 genes in Hungarian patients with sporadic Parkinson's disease. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder, with cases of either familial or sporadic origin. Several polymorphisms in a number of genes have been proved to have an important role in the development of PD. Particular attention has recently been paid to genes of the glucocerebrosidase (GBA) and the vacuolar protein sorting-associated protein 35 (VPS35). In this study, the three most common mutations (L444P, N370S and R120W) of the GBA gene and the D620N mutation of the VPS35 gene were examined in 124 Hungarian patients diagnosed with sporadic PD (SPD) and 122 control subjects. The frequency of the L444P mutation of the GBA gene proved to be higher in the PD patients (2.4%) than in the controls (0%), although the difference was not statistically significant. All the patients who carried the mutant allele were in the early-onset PD (EOPD) group. However, neither the R120W nor the N370S variant of the GBA gene nor D620N mutation of the VPS35 gene were detected among the PD cases or the controls. Even though these results suggest that the studied mutations are quite rare in SPD patients, the most frequent L444P mutation of the GBA gene may be associated with the development of EOPD in the Hungarian population. PMID- 26547033 TI - Anatomical and functional relationships between deep cerebellar nuclei and cerebellar cortical Crus II in vivo in mice. AB - We previously reported that an air-puff stimulation on the ipsilateral whisker pad evoked responses in molecular layer (ML) and Purkinje cell (PC) layer in cerebellar cortex folium Crus II. We used anterograde tracing and electrophysiological methods to investigate the anatomical and functional relationships between the trigeminal tactile response area in the cerebellar cortex Crus II and deep cerebellar nuclei (DCN) in living mice. We found that the axons of tactile activated PCs projected in anterior part (IntA) and posterior part (IntP), and dorsolateral hump (IntDL) of ipsilateral interposed cerebellar nucleus (ICN). In ICN, the tactile stimulus evoked-field potential expressed a sequence of two negative components N1 and N2, while extracellular recordings from ICN neurons revealed that an increase in spike frequency in response to tactile stimulus. When the duration of facial air-puff stimulus were >= 30 ms, stimulation off response (Roff) were observed in the ICN, but an increase in the duration of facial air-puff stimulation did not significantly affect the amplitude of Ron (N1 and N2) and Roff. The latency and time to peak of N1 in ICN were significantly shorter than that of N1 in the ML, but the latency and time to peak of N2 in ICN were significantly later than that of P1 in the ML. The present results suggest that the facial sensory information, at least in part, is transferred to ICN by PC axons from Crus II, which evokes excitation in ICN neurons. PMID- 26547034 TI - Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease. AB - Exercise has been shown to protect against cognitive decline and Alzheimer's disease (AD) progression, however the dose of exercise required to protect against AD is unknown. Recent studies show that the pathological processes leading to AD cause characteristic alterations in blood and brain inflammatory proteins that are associated with the progression of AD, suggesting that these markers could be used to diagnosis and monitor disease progression. The purpose of this study was to determine the impact of exercise frequency on AD blood chemokine profiles, and correlate these findings with chemokine brain expression changes in the triple transgenic AD (3xTg-AD) mouse model. Three month old 3xTg AD mice were subjected to 12 weeks of moderate intensity wheel running at a frequency of either 1*/week or 3*/week. Blood and cortical tissue were analyzed for expression of monocyte chemotactic protein-1 (MCP-1) and regulated and normal T cell expressed and secreted (RANTES). Alterations in blood RANTES and MCP-1 expression were evident at 3 and 6 month old animals compared to WT animals. Three times per week exercise but not 1*/week exercise was effective at reversing serum and brain RANTES and MCP-1 expression to the levels of WT controls, revealing a dose dependent response to exercise. Analysis of these chemokines showed a strong negative correlation between blood and brain expression of RANTES. The results indicate that alterations in serum and brain inflammatory chemokines are evident as early signs of Alzheimer's disease pathology and that higher frequency exercise was necessary to restore blood and brain inflammatory expression levels in this AD mouse model. PMID- 26547035 TI - NOTCH1 intracellular domain negatively regulates PAK1 signaling pathway through direct interaction. AB - p21-Activated kinase 1 (PAK1) is a serine/threonine protein kinase implicated in cytoskeletal remodeling and cell motility. Recent studies have shown that it also promotes cell proliferation, regulates apoptosis, and increases cell transformation and invasion. In this study, we showed that NOTCH1 intracellular domain (NOTCH1-IC) negatively regulated PAK1 signaling pathway. We found a novel interaction between NOTCH1-IC and PAK1. Overexpression of NOTCH1-IC decreased PAK1-induced integrin-linked kinase 1 (ILK1) phosphorylation, whereas inhibition of NOTCH1 signaling increased PAK1-induced ILK1 phosphorylation. Notably, ILK1 phosphorylation was higher in PS1,2(-/-) cells than in PS1,2(+/+) cells. As expected, overexpression of NOTCH1-IC decreased ILK1-induced phosphorylation of glycogen synthase kinase 3 beta (GSK-3beta). Furthermore, NOTCH1-IC disrupted the interaction of PAK1 with ILK1 and altered PAK1 localization by directly interacting with it. This inhibitory effect of NOTCH1-IC on the PAK1 signaling pathway was mediated by the binding of NOTCH1-IC to PAK1 and by the alteration of PAK1 localization. Together, these results suggest that NOTCH1-IC is a new regulator of the PAK1 signaling pathway that directly interacts with PAK1 and regulates its shuttling between the nucleus and the cytoplasm. PMID- 26547036 TI - Circular code motifs near the ribosome decoding center. AB - A maximal C(3) self-complementary trinucleotide circular code X is identified in genes of bacteria, eukaryotes, plasmids and viruses (Michel, 2015; Arques and Michel, 1996). A translation (framing) code based on the circular code was proposed in Michel (2012) with the identification of several X circular code motifs (X motifs shortly) in both ribosomal RNAs (rRNAs) and their decoding center, and transfer RNAs (tRNAs). We extended these results in two ways. First, three universal X motifs were determined in the ribosome decoding center: the X motif mAA containing the conserved nucleotides A1492 and A1493, the X motif mG containing the conserved nucleotide G530 and the X motif m with unknown biological function (El Soufi and Michel, 2014). Secondly, statistical analysis of X motifs of greatest lengths performed on different and large tRNA populations according to taxonomy, tRNA length and tRNA score showed that these X motifs have occurrence probabilities in the 5' and/or 3' regions of 16 isoaccepting tRNAs of prokaryotes and eukaryotes greater than the random case (Michel, 2013). We continue here the previous works with the identification of X motifs in rRNAs of prokaryotes and eukaryotes near the ribosome decoding center. Seven X motifs PrRNAXm conserved in 16S rRNAs of prokaryotes P and four X motifs ErRNAXm conserved in 18S rRNAs of eukaryotes E are identified near the ribosome decoding center. Furthermore, four very large X motifs of length greater than or equal to 20 nucleotides, 14 large X motifs of length between 16 and 19 nucleotides and several X motifs of length greater or equal to 9 nucleotides are found in tRNAs of prokaryotes. Some properties of these X motifs in tRNAs are described. These new results strengthen the concept of a translation code based on the circular code (Michel, 2012). PMID- 26547037 TI - New species of Torque Teno miniviruses infecting gorillas and chimpanzees. AB - Anelloviridae family is comprised of small, non-enveloped viruses of various genome lengths, high sequence diversity, sharing the same genome organization. Infections and co-infections by different genotypes in humans are ubiquitous. Related viruses were described in number of mammalian hosts, but very limited data are available from the closest human relatives - great apes and non-human primates. Here we report the 100% prevalence determined by semi-nested PCR from fecal samples of 16 captive primate species. Only the Mandrillus sphinx, showed the prevalence only 8%. We describe three new species of gorillas' and four new species of chimpanzees' Betatorqueviruses and their co-infections in one individual. This study is also first report and analysis of nearly full length TTMV genomes infecting gorillas. Our attempts to sequence the complete genomes of anelloviruses from host feces invariably failed. Broader usage of blood /tissue material is necessary to understand the diversity and interspecies transmission of anelloviruses. PMID- 26547038 TI - History and genomic sequence analysis of the herpes simplex virus 1 KOS and KOS1.1 sub-strains. AB - A collection of genomic DNA sequences of herpes simplex virus (HSV) strains has been defined and analyzed, and some information is available about genomic stability upon limited passage of viruses in culture. The nature of genomic change upon extensive laboratory passage remains to be determined. In this report we review the history of the HSV-1 KOS laboratory strain and the related KOS1.1 laboratory sub-strain, also called KOS (M), and determine the complete genomic sequence of an early passage stock of the KOS laboratory sub-strain and a laboratory stock of the KOS1.1 sub-strain. The genomes of the two sub-strains are highly similar with only five coding changes, 20 non-coding changes, and about twenty non-ORF sequence changes. The coding changes could potentially explain the KOS1.1 phenotypic properties of increased replication at high temperature and reduced neuroinvasiveness. The study also provides sequence markers to define the provenance of specific laboratory KOS virus stocks. PMID- 26547039 TI - Molecular characterization of Myf5 and comparative expression patterns of myogenic regulatory factors in Siniperca chuatsi. AB - Myogenic regulatory factors (MRFs) are muscle-specific basic helix-loop-helix (bHLH) transcription factor that plays an essential role in regulating skeletal muscle development and growth. To investigate molecular characterization of Myf5 and compare the expressional patterns of the four MRFs, we cloned the Myf5 cDNA sequence and analyzed the MRFs expressional patterns using quantitative real-time polymerase chain reaction in Chinese perch (Siniperca chuatsi). Sequence analysis indicated that Chinese perch Myf5 and other MRFs shared a highly conserved bHLH domain with those of other vertebrates. Sequence alignment and phylogenetic tree showed that Chinese perch MRFs had the highest identity with the MRFs of Epinephelus coioides. Spatio-temporal expressional patterns revealed that the MRFs were primarily expressed in muscle, especially in white muscle. During embryonic development period, Myf5, MyoD and MyoG mRNAs had a steep increase at neurula stage, and their highest expressional level was predominantly observed at hatching period. Whereas the highest expressional level of the MRF4 was observed at the muscular effect stage. The expressional patterns of post-embryonic development showed that the Myf5, MyoD and MyoG mRNAs were highest at 90 days post-hatching (dph). Furthermore, starvation and refeeding results showed that the transcription of the MRFs in the fast skeletal muscle of Chinese perch responded quickly to a single meal after 7 days of fasting. It indicated that the MRFs might contribute to muscle recovery after refeeding in Chinese perch. PMID- 26547040 TI - Gene-expression profile of developing pollen tube of Pyrus bretschneideri. AB - Pollen is an ideal model system for investigation of cell growth. In order to better understand the molecular biology mechanisms of the process of pear pollen tube development, RNA sequencing (RNA-Seq) technology was used to characterize the expression of genes during four development stages of pear pollen, including mature pollen grains (MP), hydrated pollen grains (HP), growing pollen tubes (PT) and stopped-growth pollen tubes (SPT). The four libraries generated a total of 47,072,151 clean reads that were mapped and assembled into 21,394 genes. Transcripts from the four stages were classified into 38 functional subcategories. Between MP and HP, 305 genes were differentially expressed, and 502 genes were differentially expressed between HP and PT. More importantly, we have observed that 2208 genes were differentially expressed between PT and SPT, and this is the first report of the gene expression comparison between the two development stages. Eight of the differentially expressed genes were randomly selected to confirm the RNA-Seq results by quantitative real-time PCR (qRT-PCR). Taken together, this research provides a platform for future research on pear pollen tube growth and growth cessation. PMID- 26547041 TI - Removal of cyanide compounds from coking wastewater by ferrous sulfate: Improvement of biodegradability. AB - The effect of ferrous sulfate (FeSO4) treatment on the removal of cyanide compounds and the improvement of biodegradability of coking wastewater were investigated by varying Fe:TCN molar ratios. Results suggested that the reaction between FeSO4 and coking wastewater was a two-step process. At the first step, i.e., 0<=Fe:TCN<=1.0, the reaction mechanisms were dominated by the precipitation of FeS, the complexation of CN(-), and the coagulation of organic compounds. The COD of coking wastewater decreased from 3748.1 mg/L to 3450.2 mg/L, but BOD5:COD (B/C) was improved from 0.30 to 0.51. At the second step, i.e., 1.0 30 MUM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 MUM (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined. PMID- 26547058 TI - Nonparametric association analysis of bivariate left-truncated competing risks data. AB - We develop time-varying association analyses for onset ages of two lung infections to address the statistical challenges in utilizing registry data where onset ages are left-truncated by ages of entry and competing-risk censored by deaths. Two types of association estimators are proposed based on conditional cause-specific hazard function and cumulative incidence function that are adapted from unconditional quantities to handle left truncation. Asymptotic properties of the estimators are established by using the empirical process techniques. Our simulation study shows that the estimators perform well with moderate sample sizes. We apply our methods to the Cystic Fibrosis Foundation Registry data to study the relationship between onset ages of Pseudomonas aeruginosa and Staphylococcus aureus infections. PMID- 26547059 TI - Pictorial Cigarette Warning Labels: Effects of Severity and Likelihood of Risk Messages. AB - INTRODUCTION: Pictorial cigarette warning labels often contain text-messages about severity of health risks and less often about the likelihood of health risks. We aimed to examine the influence of severity of risk versus likelihood of risk text-messages on information-seeking behavior. METHODS: Study 1: An experimental study with a 2 (severity) * 2 (likelihood) between-subjects design (n = 260); Study 2: An experimental study with a 2 (severity) * 2 (likelihood) * 2 (picture) between-subjects design (n = 537). Main outcome measures were information-seeking intention and information-seeking behavior (accepting a brochure about smoking cessation in Study 1; clicking on a link to a smoking cessation webpage in Study 2). RESULTS: In Study 1, exposure to likelihood text messages was associated with more information-seeking behavior but not with attitudes and intention to quit. In Study 2, exposure to likelihood text-messages was not associated with information-seeking behavior, but was associated with higher warning label ratings and with more positive attitudes towards quitting when it was a pictorial cigarette warning label; exposure to severity text messages was associated with higher warning label ratings and higher risk perceptions. Presence of a picture with smokers' diseased lungs in Study 2 was associated with higher warning label ratings and with higher risk perceptions, but did not influence attitudes and intention to quit. CONCLUSIONS: We found preliminary indications that pictorial cigarette labels with likelihood of risk text-messages may be effective in influencing behavior. However, results from our two studies were not consistent. Therefore, future studies should examine this further. IMPLICATIONS: Although we can only draw preliminary conclusions from our study that should be replicated in future studies, our findings suggest that it is worthwhile to further explore the addition of likelihood of risk text-messages to pictorial cigarette warning labels, which is not the current practice in most countries. PMID- 26547060 TI - Active and Passive Smoking and Serum Total Bilirubin in a Rural Korean Population. AB - INTRODUCTION: Serum bilirubin is an endogenous antioxidant biomarker and its low level is a potential risk factor for smoking related health disorders. This study investigated the association of cigarette smoke with serum total bilirubin among Koreans. METHODS: Between 2006 and 2011, we examined 4899 Korean adults living in a rural community. After excluding 38 participants with serum bilirubin more than 2mg/dL, 75 participants who did not report their smoking status or who had liver or bile duct disorders, and 711 participants with liver enzymes exceeding the upper reference values, we performed a cross-sectional analysis on 4075 participants. Participants were classified into four groups: never-smokers without secondhand smoke exposure (SHSE), never-smokers with SHSE, former smokers, and active smokers. Serum total bilirubin concentration was measured using the enzyme method. RESULTS: Compared to never-smokers without SHSE, never smokers with SHSE (beta = -0.025 mg/dL), former smokers (beta = -0.049 mg/dL), and active smokers (beta = -0.149 mg/dL) had significantly lower serum bilirubin even after adjusting for demographic factors, study year, alanine aminotransferase, gamma-glutamyl transferase, hemoglobin, lifestyle factors, and chronic diseases. A sex-stratified analysis indicated that for men, former smokers and active smokers were significantly associated with having lower bilirubin when compared to never-smokers without SHSE. However, for women, never smokers with SHSE and active smokers were significantly associated with having lower bilirubin when compared to never-smokers without SHSE. CONCLUSION: Our findings suggest that both active and passive cigarette smoking are associated with low serum bilirubin among Korean adults. IMPLICATIONS: Our results suggest that not only active smoking but also passive smoking including SHSE can have an influence on decreasing serum bilirubin levels. With this different point of view, our study supports efforts to create smoke-free environments in order to foster more favorable serum bilirubin profiles, which may improve endothelial function and reduce the risk of cardiovascular disease. PMID- 26547061 TI - Use of High-Nicotine/Tar-Yield (Full-Flavor) Cigarettes and Risk for Nicotine Dependence in Nationally Representative Samples of US Smokers. AB - INTRODUCTION: The present study examines whether use of machine-estimated high nicotine/tar-yield (full-flavor) cigarettes predicts greater risk of nicotine dependence after controlling for the influence of potential confounding factors in US nationally representative samples. METHODS: Data were obtained from multiple years of the National Survey on Drug Use and Health (NSDUH). Nicotine dependence was measured by (1) the Nicotine Dependence Syndrome Scale and (2) latency to first cigarette after waking. Associations between use of high nicotine/tar-yield cigarettes and risk for nicotine dependence were examined using multiple logistic regression. RESULTS: The odds of nicotine dependence were reliably greater among users of high- compared to lower-nicotine/tar-yield cigarettes even after adjusting for sociodemographic and other smoking characteristics (Ps < .0001). This relationship was (1) generally graded across differing nicotine/tar-yield cigarettes, (2) discernible across two definitions of nicotine dependence and multiple NSDUH survey years, and (3) observed among adult and adolescent smokers. CONCLUSION: Use of high-nicotine/tar-yield cigarettes is associated with increased odds of nicotine dependence, a relationship that has important tobacco regulatory implications. Whether the widespread marketing and availability of high-nicotine/tar-yield cigarettes is increasing risk of nicotine dependence among US smokers warrants further research. IMPLICATIONS: This study adds additional empirical evidence to the relation of machine measured high-yield cigarettes and likelihood of nicotine dependence, and draws some implications in regards to regulation. PMID- 26547062 TI - The Dynamic Role of Urban Neighborhood Effects in a Text-Messaging Adolescent Smoking Intervention. AB - INTRODUCTION: Neighborhood features such as the density of tobacco outlets relative to one's home and evaluations of safety of one's activity space (routine locations), are known to influence health behaviors. Understanding the time varying nature of these aspects of the urban ecology provides unique insights into the dynamic interactions of individuals and their environments. METHODS: The present study tested the time-varying effects of tobacco outlets and perceived safety within a randomized controlled trial of an adolescent text-messaging smoking intervention. We used ecological momentary assessment data (EMA) from an automated text-messaging smoking cessation randomized trial with 197 primarily African American urban adolescents. We employed a time-varying effect model to estimate the effects of density of tobacco outlets within one-half mile of participants' home locations (time-invariant covariate) and evaluations of safety of their activity space (time-varying covariate) on momentary smoking over 6 months by treatment condition. The time-varying effect model approach models behavioral change and associations of coefficients expressed dynamically and graphically represented as smooth functions of time. RESULTS: Differences in trajectories of smoking between treatment conditions were apparent over the course of the study. During months 2 and 6, the association between tobacco outlet density and smoking was significantly stronger in the control condition, suggesting treatment dampens this association during these time periods. The intervention also significantly reduced the association of perceived safety and smoking among the treatment condition during months 3 through 6. CONCLUSIONS: Results support testing the time-varying effects of urban ecological features and perceptions of safety among adolescents in text-based smoking cessation interventions. IMPLICATIONS: This study makes a unique contribution towards understanding the time-varying effects of urban neighborhoods on adolescent tobacco use within the context of a text-delivered intervention. Helping to adjust the long-held conceptualization of intervention effects as a static outcome, to that of a dynamic, time-varying process, is an important contribution of this study. The ability to specify when behavioral change occurs within the context of a randomized control trial provides understanding into the time varying treatment effects of text-based smoking intervention. For example, researchers can modify the intervention to have strategically timed booster sessions that align with when the odds of smoking begin to increase in order to provide more precise treatment. The current study results show that increasing support to participants during months 2 and 4 may help suppress smoking over the course of a 6-month intervention. PMID- 26547063 TI - Prolapse repair with and without apical resuspension-Practice patterns among certifying American urologists. AB - AIMS: To examine surgeon characteristics in certifying urologists performing prolapse surgeries. Anterior compartment prolapse is often associated with apical prolapse, with high rates of recurrence when anterior repair is performed without apical resuspension. METHODS: Six-month case log data of certifying urologists between 2003 and 2013 was obtained from the American Board of Urology (ABU). Cases with a CPT code for common prolapse repairs in females >=18 years were analyzed. RESULTS: Among 2,588 urologists logging at least one prolapse surgery and a total of 30,983 surgeries, 320 (1.0% of all cases) uterosacral ligament suspension, 3,673 (11.9%) sacrospinous ligament suspension, and 2,618 (8.4%) abdominal sacrocolpopexy were identified. The remaining 14,585 cases were logged as anterior repair. 54.7% of anterior repairs did not include apical suspension. The proportion of anterior repairs without apical suspension has decreased from 77.7% in 2004 to 41.4% in 2012 (P < 0.001). Female subspecialists before 2011 performed anterior repair without apical suspension in 58.5%, versus 70.3% by all others. Since 2011 there has been a decrease in number of anterior repairs without apical suspension, notably in those applying for Female Pelvic Medicine and Reconstructive Surgery (FPMRS) certification (17.1% vs. 30.7% by all other urologists, P < 0.001); nonacademically affiliated urologists are 2.1 times more likely to report anterior repair without apical suspension than academically affiliated colleagues (P < 0.001). CONCLUSIONS: The proportion of prolapse repairs reported as anterior repairs without apical suspension is decreasing, although it remains a substantial portion. Recent log year, FPMRS, and academic affiliation were associated with prolapse repairs addressing apical support. Neurourol. Urodynam. 36:344-348, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26547064 TI - T-Regulatory Cells as Part of Strategy of Immune Evasion by Pathogens. AB - Under physiological conditions, regulatory processes can suppress the immune response after elimination of a pathogen and restore homeostasis through the destruction and suppression of obsolete effector cells of the immune system. The main players in this process are T-regulatory cells (Tregs) and immature dendritic cells, which suppress the immune response by their own products and/or by inducing synthesis of immunosuppressive interleukins IL-10, IL-35, and transforming growth factor (TGF-beta) by other cells. This mechanism is also used by widespread "successful" pathogens that are capable of chronically persisting in the human body - herpes virus, hepatitis viruses, human immunodeficiency virus, Mycobacterium tuberculosis, Helicobacter pylori, and others. During coevolution of microbial pathogens and the host immune system, the pathogens developed sophisticated strategies for evading the host defense, so-called immune evasion. In particular, molecular structures of pathogens during the interaction with dendritic cells via activating and inhibitory receptors can change intracellular signal transduction, resulting in block of maturation of dendritic cells. Immature dendritic cells become tolerogenic and cause differentiation of Tregs from the conventional T-cell CD4+. Microbial molecules can also react directly with Tregs through innate immune receptors. Costimulation of Toll-like receptor 5 (TLR5) by flagellin increases the expression of the transcription factor Foxp3, which increases the suppressive activity of Treg cells. From all evasion mechanisms, the induction of immunosuppression by Treg through IL-10, IL 35, and TGF-beta appears most effective. This results in the suppression of inflammation and of adaptive immune responses against pathogens, optimizing the conditions for the survival of bacteria and viruses. PMID- 26547065 TI - Natural Compounds: Role in Reversal of Epigenetic Changes. AB - The hallmarks of carcinogenesis are characterized by alterations in the expression of multiple genes that occur via genetic and epigenetic alterations, leading to genome rearrangements and instability. The reversible process of epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression that alter phenotype without any change in the DNA sequence, is recognized as a key mechanism in cancer cell metabolism. Recent advancements in the rapidly evolving field of cancer epigenetics have shown the anticarcinogenic potential of natural compounds targeting epigenetic mechanism as a common molecular approach for cancer treatment. This review summarizes the potential of natural chemopreventive agents to reverse cancer-related epigenetic aberrations by regulating the activity of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. Furthermore, there is impetus for determining novel and effective chemopreventive strategies, either alone or in combination with other anticancer agents that exhibit similar properties, for improving the therapeutic aspects of cancer. PMID- 26547066 TI - Heat Stress-Induced Transcriptional Repression. AB - Heat stress is one of the most popular models for studying the regulation of gene expression. For decades, researchers' attention was focused on the study of the mechanisms of transcriptional activation of stress-induced genes. Although the phenomenon of heat stress-induced global transcriptional repression is known for a long time, the exact molecular mechanisms of such a repression are poorly explored. In this mini-review, we attempt to summarize the existing experimental data on heat stress-induced transcriptional repression. PMID- 26547067 TI - Structural and Dynamic Changes in Mitochondria of Rat Myocardium under Acute Hypoxic Hypoxia: Role of Mitochondrial ATP-Dependent Potassium Channel. AB - The ultrastructure and spatial localization of mitochondria (MC) in the myocardium of rats exposed to a 30-min hypoxic hypoxia were investigated. The mitochondrial structure was found to undergo changes; however, marked necrotic injuries were not observed. Changes occurring in the myocardium are aimed at the intensification of energy processes. This shows up as an increase in the number of MC in the subsarcolemmal zone of the myocardium and changes in the surface of the sublemmal membrane due to its bending around mitochondria, which improves the diffusion of oxygen into MC. In addition, the division of MC is enhanced, which partially explains the increase in their total number. In structurally altered MC with intact membrane, electron dense formations with small diameter appear, which probably represent newly formed organelles (microMC). In normoxia, changes of this kind do not occur. It was found that the ATP-dependent K+ channel is involved in the regulation of the morphological state of MC under hypoxic hypoxia. The activator of the channel diazoxide increases the number of newly formed microMC, and the channel inhibitor 5HD significantly prevents their formation. Possible mechanisms of structural and dynamic changes in rat myocardial MC under acute hypoxic hypoxia are discussed. PMID- 26547068 TI - Coxsackievirus B3 Induces Autophagic Response in Cardiac Myocytes in vivo. AB - Viral myocarditis is a common disease that contributes to dilated cardiomyopathy or heart failure. Coxsackievirus B (CVB) is one of the major causative pathogens of viral myocarditis. Previous studies have shown that autophagy is exploited to promote CVB replication in cell lines. To study whether cardiac myocytes respond to CVB infection in a similar way, viral myocarditis was established by the inoculation of 3-week-old BALB/c mice with CVB3. Electron microscopic observation showed that autophagosome-like vesicles were induced in the cardiac myocytes of mice infected by CVB3 at 3, 5, and 7 days after viral infection. The lipidated microtubule-associated protein 1 light chain 3 (LC3), LC3-II, was also significantly increased in both myocardium and the cardiac myocytes extracted from the ventricles of mice infected with CVB3. The increased LC3-II coincided with high level of viral RNA and proteins in both myocardium and isolated cardiac myocytes. Moreover, viral protein synthesis was significantly decreased in primary cardiac myocytes by the treatment with 3-methyladenine, an inhibitor of autophagy. The expression and the phosphorylation of extracellular signal regulated kinase (ERK) were also increased in both myocardium and in the isolated cardiac myocytes of the virus-infected mice, while the interplay of ERK with autophagic response remains to be studied. This study demonstrated that cardiac myocytes respond to CVB3 infection by increased formation of autophagosomes in vivo, which might be exploited for viral replication. PMID- 26547069 TI - Repair of Clustered Damage and DNA Polymerase Iota. AB - Multiple DNA lesions occurring within one or two turns of the DNA helix known as clustered damage are a source of double-stranded DNA breaks, which represent a serious threat to the cells. Repair of clustered lesions is accomplished in several steps. If a clustered lesion contains oxidized bases, an individual DNA lesion is repaired by the base excision repair (BER) mechanism involving a specialized DNA polymerase after excising DNA damage. Here, we investigated DNA synthesis catalyzed by DNA polymerase iota using damaged DNA templates. Two types of DNA substrates were used as model DNAs: partial DNA duplexes containing breaks of different length, and DNA duplexes containing 5-formyluracil (5-foU) and uracil as a precursor of apurinic/apyrimidinic sites (AP) in opposite DNA strands. For the first time, we showed that DNA polymerase iota is able to catalyze DNA synthesis using partial DNA duplexes having breaks of different length as substrates. In addition, we found that DNA polymerase iota could catalyze DNA synthesis during repair of clustered damage via the BER system by using both undamaged and 5-foU-containing templates. We found that hPCNA (human proliferating cell nuclear antigen) increased efficacy of DNA synthesis catalyzed by DNA polymerase iota. PMID- 26547070 TI - Natural Larval Diet Differently Influences the Pattern of Developmental Changes in DNA 5-Methylcytosine Levels in Apis mellifera Queens as Compared with Workers and Drones. AB - The principal mechanism of gene activation/silencing is DNA 5-methylcytosine methylation. This study was aimed at determining global DNA methylation levels in larvae, prepupae, pupae, and 1-day-old adults of Apis mellifera queens, workers and drones. The Imprint Methylated DNA Quantification Kit MDQ1 was used. Percentages of DNA 5-methylcytosine were low and relatively similar in the larvae of all the castes until 4th day of larval development (3-5%). However, they were higher in the drone and worker larvae than in the queen larvae. Generally, the developmental patterns of changes in the DNA methylation levels were different in the queens in comparison with the drones and workers. While methylation increased in the queens, it decreased in the drones and workers. Methylated DNA methylcytosine percentages and weights in the queen prepupae (15%, 9.18 ng) and pupae (21%, 10.74 ng) were, respectively, three and four times higher than in the worker/drone brood of the same age (2.5-4%, 0.03-0.07 ng). Only in the queens, after a substantial increase, did DNA methylation decrease almost twice between the pupal stage and queen emergence (from 21% and 10.74 ng to 12% and 6.78 ng). This finding seems very interesting, particularly for experimental gerontology. PMID- 26547071 TI - Parallel G-Quadruplexes Formed by Guanine-Rich Microsatellite Repeats Inhibit Human Topoisomerase I. AB - Using UV and CD spectroscopy, we studied the thermodynamic stability and folding topology of G-quadruplexes (G4), formed by G-rich fragments in human microsatellites that differ in the number of guanosines within the repeating unit. The oligonucleotides d(GGGT)4 and d(GGT)4 were shown to form propeller-type parallel-stranded intramolecular G-quadruplexes. The G4 melting temperature is dramatically decreased (by more than 45 degrees C) in the transition from the tri G-tetrad to the bi-G-tetrad structure. d(GT)n-repeats do not form perfect G quadruplexes (one-G-tetrad); folded G4-like conformation is not stable at room temperature and is not stabilized by monovalent metal ions. The minimum concentration of K+ that promotes quadruplex folding of d(GGT)4 was found to depend on the supporting Na+ concentration. It was demonstrated for the first time that the complementary regions flanking G4-motifs (as in d(CACTGG-CC-(GGGT)4 TA-CCAGTG)) cannot form a double helix in the case of a parallel G4 due to the steric remoteness, but instead destabilize the structure. Additionally, we investigated the effect of the described oligonucleotides on the activity of topoisomerase I, one of the key cell enzymes, with a focus on the relationship between the stability of the formed quadruplexes and the inhibition degree of the enzyme. The most active inhibitor with IC50 = 0.08 uM was the oligonucleotide d(CACTGG-CC-(GGGT)4-TA-CCAGTG), whose flanking G4-motif sequences reduced the extreme stability of G-quadruplex formed by d(GGGT)4. PMID- 26547072 TI - Double Subgenomic Promoter Control for a Target Gene Superexpression by a Plant Viral Vector. AB - Several new deconstructed vectors based on a potexvirus genome sequence for efficient expression of heterologous proteins in plants were designed. The first obtained vector (AltMV-single), based on the Alternanthera mosaic virus (AltMV) strain MU genome, bears a typical architecture for deconstructed plant viral vectors, i.e. a triple gene block was deleted from the viral genome and the model gene of interest was placed under control of the first viral subgenomic promoter. To enhance the efficiency of expression, maintained by the AltMV-single, another vector (AltMV-double) was designed. In AltMV-double, the gene of interest was controlled by two viral subgenomic promoters located sequentially without a gap upstream of the target gene. It was found that AltMV-double provided a significantly higher level of accumulation of the target protein in plants than AltMV-single. Moreover, our data clearly show the requirement of the presence and functioning of both the subgenomic promoters for demonstrated high level of target protein expression by AltMV-double. Taken together, our results describe an additional possible way to enhance the efficiency of transient protein expression maintained in plants by a plant viral vector. PMID- 26547073 TI - Molecular Dynamics Investigation of a Mechanism of Allosteric Signal Transmission in Ribosomes. AB - The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed. PMID- 26547074 TI - Inhibitory Effect of Polyethylene Oxide and Polypropylene Oxide Triblock Copolymers on Aggregation and Fusion of Atherogenic Low Density Lipoproteins. AB - Triblock copolymers of poly(ethylene oxide) and poly(propylene oxide) (so-called pluronics) were shown to influence the aggregation and fusion of atherogenic low density lipoproteins (atLDL) and be able to inhibit these processes. The character of the influence and the degree of the stabilizing effect depended on the structure, relative hydrophobicity, and concentration of the copolymer. Pluronics L61, P85, and L64 characterized by the hydrophilic-lipophilic balance (HLB) value from 3 to 16 had the greatest ability to suppress the aggregation of atLDL. Pluronic L81 with the higher hydrophobicity (HLB = 2) partially inhibited atLDL aggregation at low concentrations but stimulated it at high concentrations. The influence of pluronics did not have a direct connection with their ability for micelle formation, but it was realized through individual macromolecules. We suppose that effects of pluronics could be due to their interaction with the lipid component of LDL and to a possible influence of these copolymers on the structure and hydrophilic-lipophilic characteristics of lipoproteins. PMID- 26547075 TI - Acidosis and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) Attenuate Zinc/Kainate Toxicity in Cultured Cerebellar Granule Neurons. AB - Cultured cerebellar granule neurons (CGNs) are resistant to the toxic effect of ZnCl2 (0.005 mM, 3 h) and slightly sensitive to the effect of kainate (0.1 mM, 3 h). Simultaneous treatment of CGNs with kainate and ZnCl2 caused intensive neuronal death, which was attenuated by external acidosis (pH 6.5) or 5-(N-ethyl N-isopropyl)amiloride (EIPA, Na+/H+ exchange blocker, 0.03 mM). Intracellular zinc and calcium ion concentrations ([Zn2+]i and [Ca2+]i) were increased under the toxic action of kainate + ZnCl2, this effect being significantly decreased on external acidosis and increased in case of EIPA addition. Neuronal Zn2+ imaging demonstrated that EIPA increases the cytosolic concentration of free Zn2+ on incubation in Zn2+-containing solution. These data imply that acidosis reduces ZnCl2/kainate toxic effects by decreasing Zn2+ entry into neurons, and EIPA prevents zinc stores from being overloaded with zinc. PMID- 26547076 TI - Asp141 and the Hydrogen-Bond Chain Asp141-Asn109-Asp33 Are Respectively Essential for GT80 Sialyltransferase Activity and Structural Stability. AB - Sialyltransferases are key enzymes involved in the biosynthesis of biologically and pathologically important sialic acid-containing molecules in nature. In this study, the activity of a putative sialyltransferase (Pm0160) harboring an inherent mutation D141Y in the conserved DDG motif, which has been identified in GT52 and GT80 families, was restored by reverse mutation. More interestingly, a hydrogen-bond chain was found to form between three conserved residues (Asp141, Asn109, and Asp33) of GT80 sialyltransferases based on recently determined crystal structures. Our mutagenesis experiments demonstrated that the hydrogen bond chain connecting the general base Asp141 with Nbeta4, Nbeta1, and Nalpha1 plays an essential role in maintaining protein structural stability other than keeping the general base Asp141 in a productive orientation for sialic acid transfer. PMID- 26547077 TI - Mutations Enhancing Selectivity of Antitumor Cytokine TRAIL to DR5 Receptor Increase Its Cytotoxicity against Tumor Cells. AB - Tumor necrosis factor superfamily cytokine TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces apoptosis in tumor cells by binding to death receptors DR4 and DR5 without affecting normal cells. However, the therapeutic use of TRAIL is limited, because many tumor cells are resistant to it. The resistance is partially related to interaction of TRAIL with the decoy receptors DcR1 and DcR2, which do not trigger the apoptotic signal and inhibit signaling of death receptors. Previously, we designed a unique DR5-specific TRAIL mutant variant DR5-B, which binds to DR5 receptor as effectively as the original cytokine, but has practically no interaction with DR4 and DcR1 receptors, and its affinity for DcR2 is reduced 400-fold. In the present work, the cytotoxity of TRAIL and DR5-B was analyzed on 12 different tumor cell lines and two types of normal cells. In nine of 12 tumor cell lines, DR5-B killed 1.5-5.0 times more tumor cells than TRAIL, and it did not exhibit toxicity towards normal cells. Chemotherapeutic drugs such as doxorubicin, paclitaxel, and bortezomib augmented the effect of both TRAIL variants, and the enhancing effect was more pronounced for DR5-B. Half-maximal effective concentrations (EC50) for DR5-B in combination with chemotherapeutic agents were 1.5-10.0 times lower than for wild-type TRAIL. Thus, DR5-B is a promising candidate both for monotherapy and in combination with chemotherapy for treatment of TRAIL-resistant tumors. PMID- 26547078 TI - Blood Pressure Out of the Office: Its Time Has Finally Come. AB - The diagnosis of hypertension includes measurement of blood pressure out of the office by either 24-hour ambulatory monitoring or home blood pressure monitoring. These methods have led to recognition of "white coat hypertension" (WCH) and "masked hypertension" (MH). Research in the 1930s first demonstrated that blood pressures in the office were often far different from those out of the office, at a time when there was no effective treatment. International attention was focused on another imminent world war and a highly controversial election in the United States. Hypertension was not a priority for concern. From the 1950s onward: (i) epidemiology linked hypertension to risk of cardiovascular disease, (ii) effective and safe drugs for treatment of hypertension appeared, (iii) randomized clinical trials demonstrated that drug treatment of hypertension is highly effective for prevention of cardiovascular disease, and (iv) advances in technology led to development of small, portable devices for recording blood pressure noninvasively at home or during usual activities. Accurate measurement of blood pressure in "real life" is now necessary and feasible for appropriate diagnosis and assessment of treatment. Out-of-office blood pressure measurement is emerging as the standard of care for hypertension. PMID- 26547080 TI - Announcing the 2014 Violence Against Women Best Article Award Winner. PMID- 26547079 TI - Immediate Postnatal Overfeeding in Rats Programs Aortic Wall Structure Alterations and Metalloproteinases Dysregulation in Adulthood. AB - BACKGROUND: Alterations in the nutritional perinatal environment, such as intrauterine growth retardation with subsequent postnatal catch-up growth, program cardiovascular disease in adulthood, possibly through alterations in matrix metalloproteinase (MMP)-2 and -9. However, experimental evidences demonstrating that changes in the nutritional perinatal environment can program MMP-2 and -9 with subsequent alterations of vessel wall are lacking. AIM: The current study evaluated whether immediate postnatal overfeeding is able to alter vascular morphological indexes and circulating and/or vascular MMP2-2 and -9 status. METHODS: Aortic morphology (wall thickness and percentage of incomplete elastin lamellae) and circulating and aortic MMP-2 and -9 activity (measured by gelatin zymography) and aortic MMP-2 and -9 mRNA (measured by reverse transcription polymerase chain reaction (RT-PCR)) were studied in adult male rats overfed (OF) or normofed (NF) during the immediate postnatal period. RESULTS: Postnatal overfeeding induced early onset obesity. Adult OF rats presented with increased blood pressure and circulating MMP-2 and -9 activity. In the thoracic aorta, postnatal overfeeding increased wall thickness and decreased elastin integrity (as demonstrated by an increased percentage of incomplete elastin lamellae). OF rats showed enhanced aortic MMP-2 activity and MMP-9 mRNA levels. Circulating and aortic MMP-2 activity correlated positively with the percentage of incomplete elastin lamellae and aortic wall thickness, respectively. CONCLUSION: Our data demonstrate for the first time that immediate postnatal nutritional programming induces increases in circulating and aortic MMP-2 activity with parallel aortic wall alterations, such as decreased elastin integrity and enhanced thickening, showing that this experimental model is suitable for the study of perinatal nutritional programming of vascular functions. PMID- 26547081 TI - Pre-clinical medical student experience in a pediatric pulmonary clinic. AB - OBJECTIVE: Our objective was to evaluate the educational value of introducing pre clinical medical students to pediatric patients and their families in a subspecialty clinic setting. METHODS: First- and second-year medical students at the University of Michigan seeking clinical experience outside of the classroom attended an outpatient pediatric pulmonary clinic. Evaluation of the experience consisted of pre- and post-clinic student surveys and post-clinic parent surveys with statements employing a four-point Likert scale as well as open-ended questions. RESULTS: Twenty-eight first-year students, 6 second-year students, and 33 parents participated in the study. Post-clinic statement scores significantly increased for statements addressing empathic attitudes, confidence communicating with children and families, comfort in the clinical environment, and social awareness. Scores did not change for statements addressing motivation, a sense of team membership, or confidence with career goals. Students achieved their goals of gaining experience interacting with patients, learning about pulmonary diseases, and observing clinic workflow. Parents felt that they contributed to student education and were not inconvenienced. CONCLUSIONS: Students identified several educational benefits of exposure to a single pediatric pulmonary clinic. Patients and families were not inconvenienced by the participation of a student. Additional studies are warranted to further investigate the value of this model of pre-clinical medical student exposure to subspecialty pediatrics. PMID- 26547083 TI - Assessment of perioperative mortality risk in patients with infective endocarditis undergoing cardiac surgery: performance of the EuroSCORE I and II logistic models. AB - OBJECTIVES: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been established as a tool for assisting decision-making in surgical patients and as a benchmark for quality assessment. Infective endocarditis often requires surgical treatment and is associated with high mortality. This study was undertaken to (i) validate both versions of the EuroSCORE, the older logistic EuroSCORE I and the recently developed EuroSCORE II and to compare their performances; (ii) identify predictors other than those included in the EuroSCORE models that might further improve their performance. METHODS: We retrospectively studied 128 patients from a single-centre registry who underwent heart surgery for active infective endocarditis between January 2007 and November 2014. Binary logistic regression was used to find independent predictors of mortality and to create a new prediction model. Discrimination and calibration of models were assessed by receiver-operating characteristic curve analysis, calibration curves and the Hosmer-Lemeshow test. RESULTS: The observed perioperative mortality was 16.4% (n = 21). The median EuroSCORE I and EuroSCORE II were 13.9% interquartile range (IQ) (7.0-35.0) and 6.6% IQ (3.5-18.2), respectively. Discriminative power was numerically higher for EuroSCORE II {area under the curve (AUC) of 0.83 [95% confidence interval (CI), 0.75-0.91]} than for EuroSCORE I [0.75 (95% CI, 0.66 0.85), P = 0.09]. The Hosmer-Lemeshow test showed good calibration for EuroSCORE II (P = 0.08) but not for EuroSCORE I (P = 0.04). EuroSCORE I tended to over predict and EuroSCORE II to under-predict mortality. Among the variables known to be associated with greater infective endocarditis severity, only prosthetic valve infective endocarditis remained an independent predictor of mortality [odds ratio (OR) 6.6; 95% CI, 1.1-39.5; P = 0.04]. The new model including the EuroSCORE II variables and variables known to be associated with greater infective endocarditis severity showed an AUC of 0.87 (95% CI, 0.79-0.94) and differed significantly from EuroSCORE I (P = 0.03) but not from EuroSCORE II (P = 0.4). CONCLUSIONS: Both EuroSCORE I and II satisfactorily stratify risk in active infective endocarditis; however, EuroSCORE II performed better in the overall comparison. Specific endocarditis features will increase model complexity without an unequivocal improvement in predictive ability. PMID- 26547082 TI - Lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general United States child population. AB - BACKGROUND: The lower respiratory tract infection (LRTI)-associated hospitalization rate in American Indian and Alaska Native (AI/AN) children aged <5 years declined during 1998-2008, yet remained 1.6 times higher than the general US child population in 2006-2008. PURPOSE: Describe the change in LRTI associated hospitalization rates for AI/AN children and for the general US child population aged <5 years. METHODS: A retrospective analysis of hospitalizations with discharge ICD-9-CM codes for LRTI for AI/AN children and for the general US child population <5 years during 2009-2011 was conducted using Indian Health Service direct and contract care inpatient data and the Nationwide Inpatient Sample, respectively. We calculated hospitalization rates and made comparisons to previously published 1998-1999 rates prior to pneumococcal conjugate vaccine introduction. RESULTS: The average annual LRTI-associated hospitalization rate declined from 1998-1999 to 2009-2011 in AI/AN (35%, p<0.01) and the general US child population (19%, SE: 4.5%, p<0.01). The 2009-2011 AI/AN child average annual LRTI-associated hospitalization rate was 20.7 per 1,000, 1.5 times higher than the US child rate (13.7 95% CI: 12.6-14.8). The Alaska (38.9) and Southwest regions (27.3) had the highest rates. The disparity was greatest for infant (<1 year) pneumonia-associated and 2009-2010 H1N1 influenza-associated hospitalizations. CONCLUSIONS: Although the LRTI-associated hospitalization rate declined, the 2009-2011 AI/AN child rate remained higher than the US child rate, especially in the Alaska and Southwest regions. The residual disparity is likely multi-factorial and partly related to household crowding, indoor smoke exposure, lack of piped water and poverty. Implementation of interventions proven to reduce LRTI is needed among AI/AN children. PMID- 26547084 TI - Validation and application of a core set of patient-relevant outcome domains to assess the effectiveness of multimodal pain therapy (VAPAIN): a study protocol. AB - INTRODUCTION: Multimodal pain therapy (MPT) has been established accounting for biopsychosocial consideration in diagnostic and therapy. MPT seems to be effective, but comparability of studies is limited due to diversity of study designs and outcome measurements. The presented study aims to develop a core outcome set consisting of a minimum of outcome measures deemed necessary for medical and therapeutic decision-making, which must be measured in all clinical trials and non-randomised intervention studies. METHODS AND ANALYSIS: The study consists of several parts. First, the development and recommendation of preliminary core outcome domains will be based on results of a systematic review and structured online surveys. Participants of the expert panel are representatives of methodological, medical, physiotherapeutic, psychotherapeutic profession and patients suffering from chronic pain (n=25). Subsequently, candidate instruments to measure preliminary core outcome domains will be recommended by these experts. Therefore, systematic reviews on measurement properties of preliminary outcome measures will be conducted and finalised in a consensus meeting. Consented instruments and lacking psychometric properties of relevant instruments will be addressed and validated in the following part, a prospective multicentre study in multimodal pain centres on approximately 300 patients with chronic pain. Based on all previous results, a core outcome set for MPT measured in effectiveness studies and daily recordkeeping will be finalised by consensus. Statistical analyses will be performed according to methodological standards (COSMIN). ETHICS AND DISSEMINATION: The methods and procedure of the study are developed in compliance with the ethical principles of the Helsinki Declaration and Good Epidemiologic Practice. Recruitment of study participants will require approval of the study by the responsible ethics committee and signed informed consent from each participant. Pseudonymised data will be used for statistical analysis. PMID- 26547085 TI - IN SEARCH OF A FATHER: LEGAL CHALLENGES SURROUNDING POSTHUMOUS PATERNITY TESTING. AB - This article interrogates the workings of the Human Tissue Act 2004, as it applies to paternity testing by DNA analysis after the death of the putative father. We use a case series methodology more usually seen in medical research, through which we present three real case studies involving posthumous paternity testing of retained tissue. We argue that the criminal offence in section 45 of the Human Tissue Act 2004, which is being used to regulate this activity, is inappropriate and inadequate to do so. The threat of the shadow of the criminal law is too blunt an instrument to address the subtleties of the issues that arise in the context of posthumous paternity testing. We call for reform of the Human Tissue Act 2004 and the creation of a specific exception to properly deal with requests of this nature. PMID- 26547091 TI - Negotiating Access to Health Information to Promote Students' Health. AB - Access to student health information, such as immunizations, screenings, and care plans for chronic conditions, is essential for school nurses to fulfill their role in promoting students' health. School nurses typically encounter barriers to accessing health records and spend many hours attempting to retrieve health information. As a result, nurses' time is poorly utilized and students may suffer adverse outcomes including delayed school entry. In response to this pressing public health issue, a school medical advisor and director of school nurses in a local health department successfully negotiated access for school nurses to three health record systems: a state immunization tracking system, an electronic lead surveillance program, and an electronic health record system. This negotiation process is presented within a framework of the Theory of Diffusion of Innovation and provides a strategy for other school nurses seeking access to student health information. PMID- 26547088 TI - Methods of defining hypertension in electronic medical records: validation against national survey data. AB - BACKGROUND: Electronic medical records (EMR) can be a cost-effective source for hypertension surveillance. However, diagnosis of hypertension in EMR is commonly under-coded and warrants the needs to review blood pressure and antihypertensive drugs for hypertension case identification. METHODS: We included all the patients actively registered in The Health Improvement Network (THIN) database, UK, on 31 December 2011. Three case definitions using diagnosis code, antihypertensive drug prescriptions and abnormal blood pressure, respectively, were used to identify hypertension patients. We compared the prevalence and treatment rate of hypertension in THIN with results from Health Survey for England (HSE) in 2011. RESULTS: Compared with prevalence reported by HSE (29.7%), the use of diagnosis code alone (14.0%) underestimated hypertension prevalence. The use of any of the definitions (38.4%) or combination of antihypertensive drug prescriptions and abnormal blood pressure (38.4%) had higher prevalence than HSE. The use of diagnosis code or two abnormal blood pressure records with a 2-year period (31.1%) had similar prevalence and treatment rate of hypertension with HSE. CONCLUSIONS: Different definitions should be used for different study purposes. The definition of 'diagnosis code or two abnormal blood pressure records with a 2 year period' could be used for hypertension surveillance in THIN. PMID- 26547092 TI - Evaluation of a cardiopulmonary resuscitation curriculum in a low resource environment. AB - OBJECTIVES: To evaluate whether a 2-day International Liaison Committee on Resuscitation (ILCOR) Universal Algorithm-based curriculum taught in a tertiary care hospital in Liberia increases local health care provider knowledge and skill comfort level. METHODS: A combined basic and advanced cardiopulmonary resuscitation (CPR) curriculum was developed for low-resource settings that included lectures and low-fidelity manikin-based simulations. In March 2014, the curriculum was taught to healthcare providers in a tertiary care hospital in Liberia. In a quality assurance review, participants were evaluated for knowledge and comfort levels with resuscitation before and after the workshop. They were also videotaped during simulation sessions and evaluated on standardized performance metrics. RESULTS: Fifty-two hospital staff completed both pre-and post-curriculum surveys. The median score was 45% pre-curriculum and 82% post curriculum (p<0.00001). The median provider comfort level score was 4 of 5 pre curriculum and 5 of 5 post-curriculum (p<0.00001). During simulations, 93.2% of participants performed the pulse check within 10 seconds, and 97.7% performed defibrillation within 180 seconds. CONCLUSIONS: Clinician knowledge of and comfort level with CPR increased significantly after participating in our curriculum. A CPR curriculum based on lectures and low-fidelity manikin simulations may be an effective way to teach resuscitation in this low-resource setting. PMID- 26547093 TI - Single-incision laparo-thoracoscopic minimally invasive oesophagectomy to treat oesophageal cancer?. AB - OBJECTIVES: Single-incision thoracoscopic and laparoscopic procedures have been applied in treating various diseases. However, it is unknown whether such procedures are feasible in treating oesophageal cancer. METHODS: Minimally invasive oesophagectomy (MIO) with a single-incision approach in the thoracoscopic and laparoscopic procedures was attempted in 16 patients with oesophageal cancer. RESULTS: One patient was converted to laparotomy and a four port thoracoscopic procedure due to bleeding. Of the patients successfully treated with a single-port MIO, 6 underwent a McKeown procedure and 9 an Ivor Lewis procedure, including 3 cases of total laryngopharyngo-oesophagectomy with cervical pharyngogastrostomy. The mean ventilator usage of the patients after surgery was 0.3 +/- 0.6 days, the mean intensive care unit (ICU) stay was 3.8 +/- 3.1 days and the mean number of dissected lymph nodes was 28.6 +/- 14.6. One delayed anastomotic leakage occurred, and another patient developed a trachea oesophageal fistula induced by surgical clip-related tissue erosion, both of which were successfully treated by the placement of an oesophageal stent. No pulmonary complications or surgical mortalities occurred in the study. Minor complications developed in 2 patients, 1 experiencing pneumothorax and 1 postoperative delirium. When compared with traditional MIO in our series (n = 315), no statistical difference was found among patients receiving single-port MIO in terms of ventilator usage, ICU stay and the number of dissected lymph nodes. CONCLUSIONS: Single-port MIO seems to be a feasible option for treating patients with oesophageal cancer, which requires further evaluation and follow-up in the future. PMID- 26547094 TI - The needle in a haystack. PMID- 26547095 TI - Clinical evaluation of a new tumour-node-metastasis staging system for thymic malignancies proposed by the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group. AB - OBJECTIVES: The tumour-node-metastasis classification has been widely used as a guide for estimating prognosis, and is the basis for treatment decisions in patients with malignant tumours. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group have proposed a new staging system for thymic malignancies. However, its validity has not been fully established. In this study, we assessed the system's utilities and drawbacks. METHODS: We reviewed 154 consecutive patients with thymic epithelial tumours who underwent complete resection at our institution, and compared their characteristics and outcomes when classified according to the proposed system with those when classified under the Masaoka-Koga system. RESULTS: The proportion of patients with Stage I disease increased remarkably to 77.3% when using the proposed system because of the reclassification of Masaoka-Koga stages II and III diseases. Among 69 patients with Type A, AB or B1 thymoma, 68 tumours (98%) were reclassified as Stage I disease. Moreover, the proportion of Stage III and IV tumours increased in concordance with Types B2, B3 thymomas and thymic carcinoma. Under the proposed new system, the recurrence-free survival rates showed significant deterioration with increasing stage, while the overall survival curves did not. CONCLUSIONS: The newly proposed classification for thymic malignancies does not serve as a prognostic prediction model for overall survival but served as a significant imbalance of stage distribution in our cohort. However, it appears to be beneficial, especially in clinical settings and recurrence-free survival analysis. PMID- 26547098 TI - An anticoagulant too good to be true for revascularisation. PMID- 26547099 TI - Adjunctive ultrasonography in breast cancer screening. PMID- 26547101 TI - Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J START): a randomised controlled trial. AB - BACKGROUND: Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. METHODS: Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. FINDINGS: Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91.1%, 95% CI 87.2-95.0 vs 77.0%, 70.3-83.7; p=0.0004), whereas specificity was significantly lower (87.7%, 87.3-88.0 vs 91.4%, 91.1-91.7; p<0.0001). More cancers were detected in the intervention group than in the control group (184 [0.50%] vs 117 [0.32%], p=0.0003) and were more frequently stage 0 and I (144 [71.3%] vs 79 [52.0%], p=0.0194). 18 (0.05%) interval cancers were detected in the intervention group compared with 35 (0.10%) in the control group (p=0.034). INTERPRETATION: Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. FUNDING: Ministry of Health, Labour and Welfare of Japan. PMID- 26547102 TI - Phase II study of proton beam therapy as a nonsurgical approach for mucosal melanoma of the nasal cavity or para-nasal sinuses. AB - PURPOSE: The aim of this phase II study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the nasal cavity and para-nasal sinuses. MATERIALS AND METHODS: N0M0 mucosal melanoma of the nasal cavity and para-nasal sinuses were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 GyE in 15 fractions. Primary endpoint was local control rate at 1 year after treatment. Based on the results of a pilot study, the local control rate was estimated at 75%. RESULTS: Thirty-two patients were enrolled from June 2008 through October 2012. Patient characteristics were as follows: median age 73 years (range, 36-89 years); male/female ratio, 12/20; and T stage 3/4, 11/21. Local control rate at 1 year was 75.8% (95% CI: 63.8 92.4%). With a median follow-up period of 36.4 months, 3-year overall survival rate was 46.1%. The most frequent pattern of first failure was distant metastasis. The main cause of death was cancer death due to distant metastases (93.3%). CONCLUSIONS: Proton beam therapy showed sufficient local control benefits for mucosal melanoma as an alternative treatment of surgery. PMID- 26547100 TI - Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. AB - BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1.05, 95% CI 0.80-1.39; p=0.72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3.49, 95% CI 0.73-16.82; p=0.10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1.64, 1.19-2.25; p=0.002). INTERPRETATION: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING: Regado Biosciences Inc. PMID- 26547103 TI - Impaired gamete production and viability in Atlantic croaker collected throughout the 20,000 km(2) hypoxic region in the northern Gulf of Mexico. AB - The long-term impacts of recent marked increases in the incidence and extent of hypoxia (dissolved oxygen <2 mg/L) in coastal regions worldwide on fisheries and ecosystems are unknown. Reproductive impairment was investigated in Atlantic croaker collected in 2010 from the extensive coastal hypoxic region in the northern Gulf of Mexico. Potential fecundity was significantly lower in croaker collected throughout the ~20,000 km(2) hypoxic region than in croaker from normoxic sites. In vitro bioassays of gamete viability showed reductions in oocyte maturation and sperm motility in croaker collected from the hypoxic sites in response to reproductive hormones which were accompanied by decreases in gonadal levels of membrane progestin receptor alpha, the receptor regulating these processes. The finding that environmental hypoxia exposure reduces oocyte viability in addition to decreasing oocyte production in croaker suggests that fecundity estimates need to be adjusted to account for the decrease in oocyte maturation. PMID- 26547104 TI - IL12RB2 Polymorphisms correlate with risk of lung adenocarcinoma. AB - In a previous study, lack of IL-12 signaling in il12rb2 knock-out mice was found to predispose to lung adenocarcinoma (LAC). We asked whether specific polymorphisms of the human IL12RB2 gene may confer susceptibility to LAC. We studied IL12RB2 single nucleotide polymorphisms (SNPs) spanning from the promoter to the first untranslated exon of the gene. Genotypes of 49 individuals with LAC were compared with those of 93 healthy subjects. Two allele variants were found to be associated with increased susceptibility to LAC. One haplotype (hap), hap18, was more frequent in patients (18%) versus controls (6%) and significantly associated with increased probability of disease occurrence. Furthermore, IL-12 driven STAT4 phosphorylation in T cell blasts from healthy individuals was found to correlate with both single allele variants and haplotypes. In conclusion, genetically determined low signaling activity of IL-12R predisposes to the development of LAC. PMID- 26547105 TI - A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection. AB - Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-gamma, IL-4, and IL 17, whereas only IL-12 and IFN-gamma were induced by the higher-dose non adjuvanted formulation. Lastly, passive transference of the higher-dose AH adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing. PMID- 26547106 TI - Beta-adrenergic blockade increases GLUT4 and improves glycemic control in insulin treated diabetic Wistar rats. AB - OBJECTIVE: Unequivocal modulation of glycemic homeostasis by chronic beta adrenergic blockade in diabetes has never been demonstrated. This study investigates the participation of beta-adrenergic system in glycemic control and muscle glucose transporter GLUT4 expression in insulin-treated diabetic rats. METHODS: Insulin-treated diabetic Wistar (W) or spontaneously hypertensive rats (SHR) were additionally treated with propranolol, and glycemic homeostasis and expression of some target mRNAs and proteins in soleus and extensor digitorum longus (EDL) muscles were analyzed. RESULTS: Insulin improved glycemic control in both strains. Importantly, in W, propranolol promoted a further improvement in glycemic control, which was accompanied by decreased PKA and Tnf expression, and increased Slc2a4 and GLUT4 in EDL. Those effects were not observed in diabetic SHR. DISCUSSION: Propranolol-induced decrease in beta-adrenergic activity in skeletal muscles of insulin-treated diabetic Wistar rats increases GLUT4 expression in EDL, improving glycemic control. These outcomes represent a positive effect of nonselective beta-blockade, which might be extended to autonomic neuropathy. PMID- 26547107 TI - [UNE-EN ISO 15189 accreditation of the preanalytical phase of a clinical laboratory]. AB - OBJECTIVES: Description of the procedures followed in Catlab's pre-analytical area for UNE-EN ISO 15189 accreditation, and implementation of quality indicators to evaluate the standard requirements in the pre-analytical phase processes. MATERIAL AND METHODS: Description of Catlab's 2 self-developed computer applications: Catlab Program Incidents (CPI) and Refrigerator Management Program (RMP). Both of them, among other applications, documentation and quality indicators, had enabled us to achieve UNE-EN ISO 15189 accreditation and have traceability in the pre-analytical phase. RESULTS: Results of 4 quality indicators are shown. In the customers satisfaction measurement indicator, 97.3% clinicians value positively (quite/lot) different aspects of the laboratory. The indicator of pre-analytical incidents went from 7.2% in 2011 down to 4.4% in 2014. In the prompt transport of late arrival samples, 3 of the routes (33%) did not reach the acceptable target. And finally, the indicator of default opening time of sample coolers, 100% of the routes reached the desired objective in the second quarter of 2014. CONCLUSIONS: The use of those applications, allowed us to design quality control indicators of the processes in the pre-analytical phase; from sample extraction to its analytical process in the laboratory, enhancing the collaboration with extraction sites, and allowing improvement actions to be established. PMID- 26547108 TI - Importance of implementing an analytical quality control system in a core laboratory. AB - INTRODUCTION: The aim of the clinical laboratory is to provide useful information for screening, diagnosis and monitoring of disease. The laboratory should ensure the quality of extra-analytical and analytical process, based on set criteria. To do this, it develops and implements a system of internal quality control, designed to detect errors, and compare its data with other laboratories, through external quality control. In this way it has a tool to detect the fulfillment of the objectives set, and in case of errors, allowing corrective actions to be made, and ensure the reliability of the results. OBJECTIVE: This article sets out to describe the design and implementation of an internal quality control protocol, as well as its periodical assessment intervals (6 months) to determine compliance with pre-determined specifications (Stockholm Consensus(1)). MATERIALS AND METHODS: A total of 40 biochemical and 15 immunochemical methods were evaluated using three different control materials. Next, a standard operation procedure was planned to develop a system of internal quality control that included calculating the error of the analytical process, setting quality specifications, and verifying compliance. RESULTS: The quality control data were then statistically depicted as means, standard deviations, and coefficients of variation, as well as systematic, random, and total errors. The quality specifications were then fixed and the operational rules to apply in the analytical process were calculated. Finally, our data were compared with those of other laboratories through an external quality assurance program. DISCUSSION: The development of an analytical quality control system is a highly structured process. This should be designed to detect errors that compromise the stability of the analytical process. The laboratory should review its quality indicators, systematic, random and total error at regular intervals, in order to ensure that they are meeting pre-determined specifications, and if not, apply the appropriate corrective actions. PMID- 26547109 TI - Brodalumab, a human anti-interleukin-17-receptor antibody in the treatment of Japanese patients with moderate-to-severe plaque psoriasis: Efficacy and safety results from a phase II randomized controlled study. AB - BACKGROUND: Brodalumab (KHK4827 or AMG 827) is a human monoclonal antibody that binds to the human interleukin (IL)-17 receptor A and blocks the biological activities of IL-17A, IL-17F, IL-17A/F, and IL-17E also known as IL-25. A 12-week phase 2 trial in the USA, Europe, and other countries showed the good efficacy of brodalumab in treating patients with moderate to severe plaque psoriasis. However, with the exception of a phase 1 study, a clinical trial of brodalumab in psoriasis has not been undertaken in Japan. OBJECTIVE: To evaluate the efficacy and safety of brodalumab in Japanese patients with moderate-to-severe plaque psoriasis, including psoriatic arthritis, in a multicenter, randomized, double blind, placebo-controlled, parallel-group comparative phase 2 study, and to assess the pharmacokinetics of brodalumab. METHODS: Japanese patients with moderate-to-severe plaque psoriasis, including psoriatic arthritis, were randomized to receive 70mg, 140mg, or 210mg of brodalumab, or placebo, injected subcutaneously at baseline and weeks 1, 2, 4, 6, 8, and 10. The primary efficacy endpoint was the percentage improvement in the Psoriasis Area and Severity Index (PASI) score from baseline to week 12. Secondary efficacy endpoints included the percentage of patients with >=75% reduction of PASI scores (PASI 75), >=90% (PASI 90), and 100% (PASI 100) and the percentage of patients with a static physician's global assessment (sPGA) of 0 (clear) or 1 (almost clear) at week 12. Safety was evaluated by assessing the adverse events (AE) and the patients' hematologic and laboratory values. RESULTS: At week 12, the mean percentage improvements in the PASI scores were 37.7%, 82.2%, 96.8%, and 9.4% in the 70mg, 140mg, 210mg, and placebo groups, respectively, (p<0.001 for all comparisons with placebo). The percentage of patients with PASI 75, PASI 90, and PASI 100 at week 12 were 7.9%, 2.6%, and 0%, respectively, in the placebo group, 25.6%, 15.4%, and 2.6%, respectively, in the 70mg brodalumab group, 78.4%, 64.9%, and 35.1%, respectively, in the 140mg brodalumab group, and 94.6%, 91.9%, and 59.5%, respectively, in the 210mg brodalumab group. Concerning psoriatic arthritis, at week 12, the numbers (%) of patients fulfilling the American College of Rheumatology response criteria for a 20% improvement were 0 (0%) in the placebo group, and 1 (20%), 2 (40%), and 4 (100%) in the 70mg, 140mg, and 210mg brodalumab groups, respectively. The percentages of patients with Dermatology Life Quality Index scores of 0 or 1 at week 12 were greater in the 140mg (54.1%) and the 210mg (56.8%) brodalumab groups than in the placebo group (8.8%). The most common AE in the brodalumab groups were nasopharyngitis (12.4% vs. 7.9% for placebo), diarrhea (5.3% vs. 0%), upper respiratory tract inflammation (3.5% vs. 0%), and folliculitis (3.5% vs. 0%). CONCLUSION: The rapid, robust efficacy of brodalumab and its favorable safety profile shown in the current study confirm previous studies conducted in Caucasian people, further warranting the use of brodalumab as a new treatment option for plaque psoriasis. PMID- 26547110 TI - First experience with extended release tacrolimus in the treatment of adult patients with severe, difficult to treat atopic dermatitis: Clinical efficacy, safety and dose finding. PMID- 26547111 TI - Rhododenol-induced leukoderma in a mouse model mimicking Japanese skin. AB - BACKGROUND: Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol((r)) (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced leukoderma. OBJECTIVE: The etiology of RD-induced leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of leukoderma by topically applying RD. METHODS: Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice. RESULTS: The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress. CONCLUSIONS: These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity. PMID- 26547112 TI - Bi-allelic nonsense mutations inABHD5 underlie a mild phenotype of Dorfman Chanarin syndrome. PMID- 26547113 TI - Comparison of the perception of the educational atmosphere by nursing students in a Chilean university. AB - BACKGROUND: Learning is situated within an environment, cannot be dissociated from the context in which it occurs and impacts upon the results of student learning, obtaining better results in favorably perceived environments. The elements that mostly affect that perception are the curricular contents, teaching methodologies, and the handling of the education atmosphere. These elements, complex and dynamic, are perceived differently according to the level of the career. Some studies establish that the perception improves as the student progresses in the career, while others show the opposite. OBJECTIVES: Measure the perception of nursing students of the education atmosphere and compare the differences among the distinct levels of the career. DESIGN: This was a longitudinal prospective study. Settings and Participants The study was conducted with nursing students from the class of 2011 at Universidad de los Andes, Santiago-Chile. Sixty-one students complied with inclusion criteria and were surveyed in second (n=55), third (n=51), and fourth (n=34) years, during 2012, 2013, and 2014, respectively. METHODS: The Dundee Ready Education Environment Measure questionnaire was applied. The STATA 10 program was used for analysis and the one way ANOVA was use to compare the results. RESULTS: The average perception of the education atmosphere was 133/200, obtaining more positive aspects than negative ones. Students improve their perception as they advance in the career. The three measurements repeat five items as weaknesses and 12 as strengths. CONCLUSIONS: It is convenient to bear in mind the difficulties of students to reconcile the clinical experiences with the theoretical classes on campus by continuous assessing the academic load and the demands made by each professor. Some strategies would include promoting professors' greater closeness with the students, considering travel times in the academic programming, as well as applying the basic theoretical contents in real clinical cases to give them relevance. PMID- 26547114 TI - Did Schon really say that? A response to Comer. PMID- 26547115 TI - Anticoagulant conversion in the elderly: pitfalls. AB - The prevalence of medical conditions representing a risk for thromboembolic complications and requiring antithrombotic therapy increases gradually with age. Two cases of fatal noncritical organ bleeding complication that occurred during the conversion period from initial fondaparinux to vitamin K antagonist are presented. An 81-year-old obese female patient (body mass index 43 kg/m(2)) with previous postoperative thrombosis underwent uneventful total knee replacement under spinal anesthesia. She presented with popliteal hematoma during conversion to oral anticoagulant. A 92-year-old female patient (body mass index 33 kg/m(2)) with left lower limb thrombosis was referred to our orthopedics department from her senior citizens' home for right lower limb hematoma and ischemia that occurred during conversion to oral anticoagulant. Thromboembolic and bleeding events in the elderly are real public health problems. Specific guidelines dedicated to this particular population are needed, which will improve the management of anticoagulation and decrease risk of complications. PMID- 26547116 TI - Abbreviated right-sided heart echocardiogram and the STOP-Bang questionnaire-a useful relationship for preoperative patient evaluation? AB - STUDY OBJECTIVE: The aims of this study were to (1) explore the incidence of right-sided heart dysfunction (RHD) and STOP-Bang questionnaire responses consistent with obstructive sleep apnea (OSA) and (2) assess the relationship between patients with STOP-Bang questionnaire responses consistent with OSA and echocardiographic findings suggestive of RHD. DESIGN: Observational study. SETTING: Tertiary academic center preoperative clinic. PATIENTS: Two hundred patients presenting for elective surgery to the University of Utah preoperative clinic. INTERVENTION: Abbreviated transthoracic right-sided echocardiogram and STOP-Bang questionnaire. MEASUREMENTS: Tricuspid annular plane systolic excursion, tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), and the tricuspid inflow E wave to tricuspid annular tissue Doppler e' wave ratio (E/e') for the presence of RHD, as well as responses to STOP-Bang questionnaire. MAIN RESULTS: A total of 140 echocardiograms were analyzed after exclusion of participants with incomplete STOP-Bang questionnaires and inadequate images. Thirty-five patients (25%) reported 5 or more positive responses to the STOP-Bang questionnaire. Forty-six patients (35%) had abnormal right-sided heart measurements. Of the 35 patients with STOP-Bang scores 5 or greater, 11 (31%) had evidence of RHD. No correlation was observed between STOP-Bang scores and the echocardiography metrics of RHD. CONCLUSIONS: This preliminary study suggests that there are numerous sources of RHD, among one of which is sleep apnea, and/or the STOP-Bang questionnaire is not a sensitive tool for predicting RHD. We conclude that although the STOP-Bang questionnaire is easy to implement in a preoperative clinical setting, it is not useful in identifying patients at risk for RHD. PMID- 26547118 TI - Dynamics of micron-sized particles in dilute and concentrated suspensions probed by dynamic ultrasound scattering techniques. AB - A novel ultrasound technique called Frequency-Domain Dynamic ultraSound Scattering (FD-DSS) was employed to determine sedimentation velocities and the diameters of microparticles in a highly turbid suspension. The paper describes the importance of the scattering vector q for dynamic scattering experiments using broadband ultrasound pulses because q (or frequency) corresponds to the spatial length scale whereas the pulses involve inevitable uncertainty in the time domain due to the frequency distribution of broadband pulse. The results obtained from Stokes velocity of monodispersed silica and polydivinylbenzene (PDVB) particles were compared to those obtained by a Field Emission Scanning Electron Microscope (FE-SEM). A novel method to extract the particle size distribution is also demonstrated based on an ultrasound scattering theory. PMID- 26547117 TI - Automated 3D ultrasound image segmentation to aid breast cancer image interpretation. AB - Segmentation of an ultrasound image into functional tissues is of great importance to clinical diagnosis of breast cancer. However, many studies are found to segment only the mass of interest and not all major tissues. Differences and inconsistencies in ultrasound interpretation call for an automated segmentation method to make results operator-independent. Furthermore, manual segmentation of entire three-dimensional (3D) ultrasound volumes is time consuming, resource-intensive, and clinically impractical. Here, we propose an automated algorithm to segment 3D ultrasound volumes into three major tissue types: cyst/mass, fatty tissue, and fibro-glandular tissue. To test its efficacy and consistency, the proposed automated method was employed on a database of 21 cases of whole breast ultrasound. Experimental results show that our proposed method not only distinguishes fat and non-fat tissues correctly, but performs well in classifying cyst/mass. Comparison of density assessment between the automated method and manual segmentation demonstrates good consistency with an accuracy of 85.7%. Quantitative comparison of corresponding tissue volumes, which uses overlap ratio, gives an average similarity of 74.54%, consistent with values seen in MRI brain segmentations. Thus, our proposed method exhibits great potential as an automated approach to segment 3D whole breast ultrasound volumes into functionally distinct tissues that may help to correct ultrasound speed of sound aberrations and assist in density based prognosis of breast cancer. PMID- 26547119 TI - Discussion paper: Conceptual comparison of student and therapeutic engagement. AB - Nurses as faculty teaching undergraduate students, require a diversity of skills to ensure that students engage in achieving the desired qualification. While it is anticipated that students have a degree of motivation to reach this goal, their varied backgrounds often mean they require additional support to assist them to engage with the learning process. It is anticipated that the tertiary institution or learning environment will have strategies to support the student from a broader perspective, but much of the engagement relies on the skill and knowledge of the nurse faculty. This discussion paper aims to promote an understanding of student engagement and argues that using aspects of therapeutic engagement can support nurse faculty to enhance the students' learning experience. Key concepts from both student and therapeutic engagement will be reviewed to provide implications, particularly for novice nurse faculty. PMID- 26547120 TI - Personality attributes of Iranian people who stutter. AB - Two recent studies from Australia and Germany have both shown that people who stutter (PWS) have elevated Neuroticism scores on the widely used NEO Five Factor Inventory (NEO-FFI) compared to individuals in a control sample. The two studies showed opposite results, however, for the personality traits Agreeableness and Conscientiousness. One reason for these opposing findings could be that the two studies were conducted in different cultural settings. Given that the effect of different cultural background on the relationship between the NEO-FFI and stuttering remains an open question, we investigated the NEO-FFI scores from 98 PWS and an age- and sex-matched control-group from a less widely studied cultural background (Iran). Overall, the present study showed, in line with a study from Germany, higher Agreeableness, but not Neuroticism, in PWS compared to normally fluent controls. To get further insights into these findings, we also contrasted both samples from Iran with a healthy matched sample from Germany. The resulting cross-cultural differences from these analyses are also discussed in the present paper. Although the present study is limited by a cross-sectional design, and so no causal conclusions can be drawn, the authors discuss whether the replicated elevated Agreeableness scores in PWS might represent a self-defense mechanism to cope with one's own speech handicap. PMID- 26547121 TI - Contrast Enhancement Patterns after Irreversible Electroporation: Experimental Study of CT Perfusion Correlated to Histopathology in Normal Porcine Liver. AB - PURPOSE: To analyze ablated tissue zones after irreversible electroporation (IRE) of porcine liver using computed tomography (CT) perfusion imaging with histopathologic correlation. MATERIALS AND METHODS: Under ultrasound and CT guidance, 10 IRE ablations were performed percutaneously in three Yorkshire pigs using a single bipolar electrode. CT perfusion imaging was performed in all pigs immediately after ablation and on day 2. Pathologic sections were prepared for correlation with histopathology (hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling stains, 5-mm-thick slices). The short diameter of different enhancing zones on CT was correlated with the gross specimen. RESULTS: CT perfusion images showed three differently enhancing zones: zone 1, inner nonenhancing zone; zone 2, middle well-defined progressive internal enhancement zone; and zone 3, outer ill-defined arterial enhancement zone with rapid washout. On histopathology, zone 1 showed a strong correlation with a pale zone, and zone 2 correlated with a red zone, together accounting for the extent of cell death. Zone 3 was outside of the ablation zone and contained inflammatory cells. Each enhancing zone had different perfusion parameters. CONCLUSIONS: CT perfusion imaging in the acute setting effectively demonstrates histopathologic tissue zones after IRE ablation. Zone 2 is unique to IRE not seen in thermal ablation, characterized by progressive intra-zonal enhancement, and its outer boundary defines the extent of cell death. PMID- 26547122 TI - Complication and Readmission Rates following Same-Day Discharge after Percutaneous Renal Tumor Ablation. AB - PURPOSE: To evaluate readmission rate and complications in patients undergoing same-day discharge following percutaneous thermal ablation of renal tumors. MATERIALS AND METHODS: Patients undergoing same-day discharge following thermal ablation of renal tumors were reviewed. The primary outcome was the rate of readmission within 30 days of same-day discharge. The secondary outcomes included the rate and clinical outcomes of periprocedural complications. RESULTS: Same-day discharge occurred in 166/174 patients (95%), of whom 2/166 (1%) required short term readmission due to pulmonary embolism and acute-on-chronic kidney injury. Both patients recovered without permanent morbidity. Admission due to complications occurred in 8/174 (5%) cases, the majority of which were related to hemorrhage. No significant differences in rates of complications or admission were found between cryoablation and RF ablation. Major complications (Clavien Dindo grade II or higher, SIR grade C or higher) occurred in 7/174 (4%) cases, the majority related to hemorrhage. All cases were detected in the standard 4 hour postprocedural observation period and managed conservatively. The mean hemorrhage volume was significantly larger in patients requiring admission versus those discharged the same day (289 mL vs 34 mL; P = .02). Higher-volume hemorrhage occurred in larger tumors (mean, 4.0 cm vs 3.0 cm; P = .04). There was no association between major complications and central tumor or age. CONCLUSIONS: Routine same-day discharge following percutaneous renal tumor thermal ablation can be performed with a low rate of short-term readmission. The majority of periprocedural complications can be managed conservatively, and patients can be discharged the same day. PMID- 26547123 TI - Simultaneous multi-slice readout-segmented echo planar imaging for accelerated diffusion-weighted imaging of the breast. AB - OBJECTIVES: Readout-segmented echo planar imaging (rs-EPI) significantly reduces susceptibility artifacts in diffusion-weighted imaging (DWI) of the breast compared to single-shot EPI but is limited by longer scan times. To compensate for this, we tested a new simultaneous multi-slice (SMS) acquisition for accelerated rs-EPI. MATERIALS AND METHODS: After approval by the local ethics committee, eight healthy female volunteers (age, 38.9 +/- 13.1 years) underwent breast MRI at 3T. Conventional as well as two-fold (2* SMS) and three-fold (3* SMS) slice-accelerated rs-EPI sequences were acquired at b-values of 50 and 800 s/mm(2). Two independent readers analyzed the apparent diffusion coefficient (ADC) in fibroglandular breast parenchyma. The signal-to-noise ratio (SNR) was estimated based on the subtraction method. ADC and SNR were compared between sequences by using the Friedman test. RESULTS: The acquisition time was 4:21 min for conventional rs-EPI, 2:35 min for 2* SMS rs-EPI and 1:44 min for 3* SMS rs EPI. ADC values were similar in all sequences (mean values 1.62 * 10(-3)mm(2)/s, p=0.99). Mean SNR was 27.7-29.6, and no significant differences were found among the sequences (p=0.83). CONCLUSION: SMS rs-EPI yields similar ADC values and SNR compared to conventional rs-EPI at markedly reduced scan time. Thus, SMS excitation increases the clinical applicability of rs-EPI for DWI of the breast. PMID- 26547124 TI - Can physiologic menstrual cycle change serum lamotrigine concentration? AB - PURPOSE: The present study aimed to compare the serum LTG levels during the early /mid-follicular (low estradiol) and mid-luteal (high estradiol) phases of the physiologic menstrual cycle. METHOD: In a cross-sectional study, 20 women with epilepsy were recruited. Participants had been on monotherapy with LTG for at least two months. All the subjects had normal menstrual cycles. Blood samples for each patient were taken whilst fasting during the early-/mid-follicular (Days 3 5) and mid-luteal phases (Days 20-24). All samples were analyzed in batched assays. A comparison of the serum LTG levels was carried out using the Mann Whitney U test Data were analyzed with the SPSS program, version 16 (SPSS Inc., Chicago, IL), p-values below 0.05 were considered significant. RESULTS: The mean serum LTG levels for the early-/mid-follicular and mid-luteal phases were 4.28+/ 2.76 mg/ml (SD) and 3.86+/-2.06 mg/ml (SD), respectively. There was no statistically significant difference in serum LTG level between the (low estradiol) early-/mid-follicular and (high estradiol) mid-luteal phases in our patients (p-value=0.23). CONCLUSION: The serum level of LTG does not alter significantly during the menstrual cycle. PMID- 26547125 TI - Lymphoepithelial carcinoma of the major salivary glands: Predictors of survival in a non-endemic region. AB - INTRODUCTION: Lymphoepithelial carcinoma (LEC) of the salivary glands is extremely rare worldwide, with studies limited to small case reports and case series from endemic areas (Southern China, Arctic Inuits) and strong association to Epstein Barr Virus (EBV). Studies on non-endemic regions are even more limited given the reality of only sporadic cases in these areas. Using the National Cancer Database (NCDB), we present the largest study on salivary LEC from a non endemic region, the United States. METHODS: A retrospective review of the NCDB from 1998-2012 for LEC of the major salivary glands was performed. Demographic and clinical variables were extracted for analysis. Multivariate COX regression was used to assess predictors of survival. RESULTS: Two hundred and thirty-eight cases were identified (0.66% of all salivary cancers). Median age at diagnosis was 62 with peak incidence in ages 50-70. Most patients were Caucasian (81.2%), without gender preference. Regional metastasis was common (45.1%) and did not significantly impact survival. Distant metastasis was rare (2%). Overall survival (OS) at 5- and 10 years was 77% and 56%. Surgery and radiotherapy significantly showed better survival outcomes than surgery alone (p<0.001). Age >62, advanced stage, and dual modality therapy were significant predictors of survival in multivariate analysis. CONCLUSION: Lymphoepithelial carcinoma in the US mostly affects an older, Caucasian demographic. Regional metastasis is common and survival is fair at 5- and 10 years. Surgery and radiation are recommended for early and advanced disease stages. Age, stage, and therapy are significant predictors of survival outcomes. PMID- 26547126 TI - Comparison of 18F-FDG PET/CT, MRI and SPECT in the diagnosis of local residual/recurrent nasopharyngeal carcinoma: A meta-analysis. AB - The objective of this study was to assess the overall diagnostic value of MRI, SPECT and 18F-FDG PET/CT in detecting local NPC residual/recurrence with a meta analysis. We performed a systematic review with meta-analyses to compare the diagnostic performance of nuclear magnetic resonance Imaging (MRI), single photon emission computed tomography (SPECT) and 18-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET/CT) as imaging modalities for the detection of local residual or recurrent nasopharyngeal carcinoma (NPC). MEDLINE, EMBASE and publisher databases were searched in December 2014. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Pooled estimation and subgroup analysis data were obtained by statistical analysis. Seventeen studies were included in the meta-analysis. The pooled sensitivity estimates for 18F-FDGPET/CT (90%) and SPECT (85%) were not significantly higher than MRI (77%) (p=0.096 and 0.164, respectively). The pooled specificity estimates for 18F-FDGPET/CT (93%) and SPECT (81%) were significantly higher than MRI (76%) (p=0.033 and 0.042, respectively). The pooled DOR (Diagnostic odds ratio) estimates for 18F-FDGPET/CT (73.27) were significantly higher than MRI (12.09) (p=0.019) while the pooled DOR estimates for SPECT (78.69) were not significantly higher than MRI (12.09) (p=0.872). For 18F FDGPET/CT, there were no significant differences between PET-CT and PET on all of the variables including sensitivity, specificity, PLR (Positive likelihood ratio), NLR (Negative likelihood ratio) and DOR (P>0.05). For SPECT, there were no significant differences between 201TI-SPECT and MIBI-SPECT on all of the variables including sensitivity, specificity, PLR, NLR and DOR (P>0.05). Both 18F FDGPET/CT and SPECT are very accurate for the detection of local residual or recurrent NPC, they are superior to MRI in distinguishing recurrent NPC from fibrosis or scar tissue after RT in irradiated fields with distortion of normal architecture. For 18F-FDGPET/CT, the diagnostic accuracy PET/CT was not significantly different than that of PET alone. For SPECT, 201TI-SPECT and MIBI SPECT have the same diagnostic accuracy. PMID- 26547127 TI - Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. AB - OBJECTIVES: Evaluate the cytotoxicity and genotoxicity of short- and long-term e cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines. MATERIALS AND METHODS: HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and gamma-H2AX immunostaining. RESULTS: E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of gamma H2AX foci, demonstrating increased DNA strand breaks. CONCLUSION: E-cigarette vapor, both with and without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed. PMID- 26547128 TI - High hemoglobin A1c levels within the non-diabetic range are associated with the risk of all cancers. AB - Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46-80 years who participated in the Japan Public Health Center-based prospective study who had HbA1c measurements available and were cancer-free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow-up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non-diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0-5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07-1.52); 1.01 (0.90-1.14); 1.28 (1.09-1.49); and 1.43 (1.14-1.80) for individuals without known diabetes and HbA1c levels <5.0%, 5.5-5.9%, 6.0-6.4%, and >=6.5%, respectively, and 1.23 (1.02 1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer. PMID- 26547129 TI - Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta Analysis of Observational Studies. AB - BACKGROUND: Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. MATERIAL AND METHODS: A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. RESULTS: A total of 13 observational studies (7 case-control and 6 cohort) were included. The pooled RR (95%CI) of kidney cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.69-0.94). In subgroup-analysis, this study found an inverse relationship between vitamin E intake and kidney cancer risk, which was not significantly modified by study design, study population, or sex distribution except in the cohort studies. CONCLUSIONS: Results of the present study suggest an inverse relationship between vitamin E intake and kidney cancer risk. However, additional well designed cohort studies and randomized controlled trials that focus on the relationship between vitamin E intake and kidney cancer risk are needed. PMID- 26547130 TI - First glimpses of the neurobiology of autism spectrum disorder. AB - Rapid progress in identifying the genes underlying autism spectrum disorder (ASD) has provided the substrate for a first wave of analyses into the underlying neurobiology. This review describes the consensus across these diverse analyses, highlighting two distinct sets of genes: 1) Genes that regulate chromatin and transcription, especially in cortical projection neurons and striatal medium spiny neurons during mid-fetal development; and 2) Genes involved in synapse development and function, especially during infancy and early childhood, and differentially expressed in the post mortem ASD brain. Both gene sets are also regulatory targets of the ASD genes CHD8 and FMRP. It remains to be seen whether these represent two independent paths to the ASD phenotype or two components of a common path. PMID- 26547131 TI - Alteration of SLP2-like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain. AB - Mitochondria play a critical role in various pathways of regulated cell death. Here we propose a novel method for detection of initial derangement of mitochondria in degenerating and dying neuronal cells. The method is based on our recent finding that antibodies directed against the cannabinoid type 1 receptor (CB1) also bind the mitochondrial stomatin-like protein 2 (SLP2) that belongs to an inner mitochondrial membrane protein complex. It is well established that SLP2 regulates mitochondrial biogenesis and respiratory functions. We now show that anti-CB1 antibodies recognize conformational epitopes but not the linear amino acid sequence of SLP2. In addition we found that anti-CB1 serum mostly labels swollen mitochondria with early or advanced stages of pathology in mouse brain while other proteins of the complex may mask epitopes of SLP2 in the normal mitochondria. Although neurons and endothelial cells in healthy brains contain occasional immunopositive mitochondria detectable with anti-CB1 serum, their numbers increase significantly after hypoxic insults in parallel with signs of cellular damage. Moreover, use of electron microscopy suggests relocation of SLP2 from its normal functional position in the inner mitochondrial membrane into the mitochondrial matrix in pathological cells. Thus, SLP2-like immunolabeling serves as an in situ histochemical target detecting early derangement of mitochondria. Anti-CB1 serum is crucial for this purpose because available anti-SLP2 antibodies do not provide selective labeling of mitochondria in the fixed tissue. This new method of detecting mitochondrial dysfunction can benefit the in vitro research of human diseases and developmental disorders by enabling analysis in live animal models. PMID- 26547132 TI - The use of combinations of monoclonal antibodies in clinical oncology. AB - Treatment with monoclonal antibodies is becoming increasingly important in clinical oncology. These antibodies specifically inhibit signaling pathways in tumor growth and/or induce immunological responses against tumor cells. By combining monoclonal antibodies several pathways may be targeted simultaneously, potentially leading to additive or synergistic effects. Theoretically, antibodies are very suitable for use in combination therapy, because of limited overlapping toxicity and lack of pharmacokinetic interactions. In this article an overview is given of preclinical and clinical data on twenty-five different combinations of antibodies in oncology. Some of these combinations have proven clinical benefit, for example the combination of trastuzumab and pertuzumab in HER2-positive breast cancer, which exemplifies an additive or synergistic effect on antitumor activity in clinical studies and the combination of nivolumab and ipilimumab, which results in significant increases in progression-free and overall survival in patients with advanced melanoma. However, other combinations may lead to unfavorable results, such as bevacizumab with cetuximab or panitumumab in advanced colorectal cancer. These combinations result in shorter progression-free survival and increased toxicity compared to therapy with a single antibody. In summary, the different published studies showed widely varying results, depending on the combination of antibodies, indication and patient population. More preclinical and clinical studies are necessary to unravel the mechanisms behind synergistic or antagonistic effects of combining monoclonal antibodies. Most research on combination therapies is still in an early stage, but it is expected that for several tumor types the use of combination therapy of antibodies will become standard of care in the near future. PMID- 26547133 TI - From HPV-positive towards HPV-driven oropharyngeal squamous cell carcinomas. AB - The incidence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is both biologically and clinically distinct from tobacco- and alcohol related OPSCC, is dramatically increasing. The finding that individuals with HPV positive local/regionally advanced OPSCC have a significantly better prognosis than their negative counterparts have led to efforts to de-escalate treatment in those patients to avoid serious side effects and to improve their long-term quality of life, while maintaining treatment efficacy. Identifying diagnostic tests that are able to distinguish cancers etiologically associated with HPV is thus becoming a pressing challenge for researchers. The purpose of this review is to provide an overview of the diagnostic tools presently available to evaluate HPV status in patients with OPSCC and, in particular, to discuss their strengths and weaknesses in identifying those infections that are the real driving force in the oropharyngeal carcinogenesis process. PMID- 26547134 TI - Social attention in ASD: A review and meta-analysis of eye-tracking studies. AB - Determining whether social attention is reduced in Autism Spectrum Disorder (ASD) and what factors influence social attention is important to our theoretical understanding of developmental trajectories of ASD and to designing targeted interventions for ASD. This meta-analysis examines data from 38 articles that used eye-tracking methods to compare individuals with ASD and TD controls. In this paper, the impact of eight factors on the size of the effect for the difference in social attention between these two groups are evaluated: age, non verbal IQ matching, verbal IQ matching, motion, social content, ecological validity, audio input and attention bids. Results show that individuals with ASD spend less time attending to social stimuli than typically developing (TD) controls, with a mean effect size of 0.55. Social attention in ASD was most impacted when stimuli had a high social content (showed more than one person). This meta-analysis provides an opportunity to survey the eye-tracking research on social attention in ASD and to outline potential future research directions, more specifically research of social attention in the context of stimuli with high social content. PMID- 26547135 TI - Zolpidem test and catatonia. AB - WHAT IS KNOWN AND OBJECTIVE: There is no consensus regarding treatment of catatonia and the main recent therapeutic progress has been the development of the zolpidem diagnostic and therapeutic test. We report on the use of this test in one of our patients. CASES SUMMARY: Mr. S. suffered from a paranoid schizophrenia. Three episodes of catatonia are described to illustrate the effect of zolpidem in a patient for whom lorazepam was ineffective or inadequate. WHAT IS NEW AND CONCLUSION: Zolpidem with appropriate testing appears to be a credible alternative to electroconvulsive therapy or increased lorazepam dosing and allows continuation of antipsychotic administration. PMID- 26547136 TI - Advanced small bowel adenocarcinoma: Molecular characteristics and therapeutic perspectives. AB - Small bowel cancer represents less than 5% of all gastrointestinal cancers, while small bowel adenocarcinoma (SBA) accounts for about one third of all cancers of the small bowel. Although SBA frequently appears sporadically, some diseases are risk factors, such as Crohn's disease and some genetic predispositions to cancer. Progress in the identification of molecular alterations suggests some similarities in carcinogenesis between SBA and colorectal cancer. Evidence levels for the treatment and prognosis of these tumors are insufficient because of the scarcity of this disease and the absence of randomized trials. Chemotherapy based on fluoropyrimidine plus a platinum salt appears to be the most effective treatment regimen in non-randomized prospective trials for advanced SBA. Targeted therapy, against the angiogenic pathway or the epidermal growth factor receptor (EGFR) pathway, for example, is not yet established, but seems promising given the over-expression of vascular epithelial growth factor (VEGF)-A or EGFR observed in SBA. Phase I and II studies are currently evaluating the safety and efficacy of these targeted therapies in SBA treatment. The low incidence of SBA should promote the development of international collaborations to improve our knowledge of the biological mechanisms underlying these tumors and to set up therapeutic trials. PMID- 26547137 TI - Celiac crisis in a multi-trauma adult patient. PMID- 26547138 TI - Mindray BC-6800 body fluid mode, performance of nucleated cells, and differential count in ascitic and pleural fluids. AB - INTRODUCTION: An accurate and rapid analysis of cells in body fluids (BFs) is important for diagnosis and follow-up in many pathological conditions. We evaluated the analytical performance of the module BF Mindray BC-6800 (BC-6800 BF) for cytometric analysis of ascitic and pleural fluids. METHODS: A total of 99 ascitic and 45 pleural samples were collected and assessed with BC-6800-BF and optical microscopy. This study also includes the evaluation of limit blank (LoB), limit detection (LoD), limit quantitation, (LoQ), carryover, linearity, and diagnostic concordance between the two methods. RESULTS: For TC-BF, LoB was 1 * 10(6) cells/L, LoD was 3 * 10(6) cells/L, and LoQ was 4 * 10(6) cells/L. Linearity was excellent (r(2) = 0.99) and carryover was negligible. TC-BF performed with the two methods showed Pearson's correlation of 0.99 (P < 0.0001), Passing-Bablok regression y = 1.04x - 1.17, and bias 33.7 cells. In ascitic fluids, polymorphonuclear cells (PMN) showed an area under curve (AUC) of 0.98 (P < 0.0001). In pleural fluids, mononuclear cells (MN) and PMN % displayed an AUC of 0.79 (P < 0.0001) and 0.93 (P < 0.0001), respectively. CONCLUSIONS: BC-6800-BF in ascitic and pleural fluids offers rapid and accurate cell and differential counts in clinically relevant concentration ranges. The use of BC-6800-BF may allow to replace routine optical counting, except for samples displaying abnormal cell counts or abnormal DIFF scattergram. PMID- 26547139 TI - Locating care at the end of life: burden, vulnerability, and the practical accomplishment of dying. AB - Home is frequently idealised as the preferred location for end-of-life care, while in-patient hospital care is viewed with suspicion and fear. Yet many people with a terminal illness spend their final days in some form of medicalised institutional setting, such as a specialist palliative care in-patient unit. Drawing on semi-structured interviews with in-patients at a specialist palliative care unit, we focus on their difficulties in finding a better place of care at the end of their life. We found that participants came to conceptualise home though a sense of bodily vulnerabilities and that they frequently understood institutional care to be more about protecting their family from the social, emotional and relational burdens of dying. For a significant number of participants the experience of dying came to be understood through what could be practically accomplished in different locales. The different locales were therefore framed around providing the best care for the patient and their family. PMID- 26547140 TI - Effects of periodontal treatment on inflammation and oxidative stress markers in patients with metabolic syndrome. AB - BACKGROUND AND OBJECTIVE: Metabolic syndrome (MetS) is a combination of risk factors (e.g. impaired glucose tolerance, hypertension, and dyslipidaemia) that significantly contribute to the development of cardiovascular diseases. The aim of the study was to compare the effects of nonsurgical periodontal treatment (NSPT) on inflammatory and oxidative stress markers in individuals with MetS and systemically healthy (SH) who were chronic periodontitis (CP). MATERIAL AND METHODS: A total of 50 patients with chronic periodontitis (25 with MetS and 25 SH) were included. Clinical periodontal measurements were recorded, and serum and whole-saliva samples were collected from all patients at baseline, and 3 and 6 mo following NSPT. The levels of fasting plasma glucose, glycated haemoglobin (HbA1c), triglyceride (TRG), total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were analysed. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and IL-10 were determined using ELISA kits, and total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) levels were measured. RESULTS: After NSPT, significant and similar improvements of all periodontal parameters were observed in both groups compared with baseline measurements. There were decreases in the levels of serum hs-CRP and IL-6, whereas increases in serum IL 10 were found in both groups, at all time points. Serum TOS and OSI showed no significant change in either group at any time point. Compared with the SH group, serum TAC levels were higher in the MetS group at baseline but lower at the 3-mo time-point. There was no difference in TAC levels between the groups at 6 mo. Saliva IL-6 was higher in the MetS group than the SH group at all time points. The levels of IL-6 and OSI in saliva decreased following NSPT in both groups, whereas salivary TAC concentrations increased. In the MetS group, TRG and HbA1c levels decreased significantly at 3 mo. CONCLUSION: NSPT decreased oxidative stress and the inflammatory status of patients with MetS and chronic periodontitis. Although similar periodontal improvements were achieved in both groups, the decreases in levels of hs-CRP and IL-6 in the MetS group did not reach the levels in the SH group. Based on these results, NSPT could be more effective in the control of systemic inflammation in patients with MetS in the short-term. PMID- 26547141 TI - Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer. AB - BACKGROUND: Solar ultraviolet (UV) radiation varies with latitude, time of day, and season. Both spectral UV composition and ambient UV dose lead to different health outcomes at different latitudes. Finding the optimal time for sun exposure, whereby the positive effects of UV exposure (vitamin D) are facilitated and the negative effects (skin cancer, photoimmunosuppression) avoided are the most important consideration in modern skin cancer prevention programs. OBJECTIVES: This paper focuses on the latitude dependency of UVB, UVA, vitamin D production, and skin cancer risk in Caucasians. METHODS: Biologically effective UVB (280-315 nm) and UVA (315-400 nm) doses were calculated using radiative transfer models with appropriate climatologic data for selected locations. Incidences of squamous cell carcinoma (SCC) and cutaneous melanoma (CM) were retrieved from cancer registries and published articles. RESULTS: Annual doses of UVA radiation decrease much less with increasing latitude than annual doses of UVB. Incidences of CM also decrease less steeply with increasing latitude than incidences of SCC. As SCC is caused mainly by UVB, these observations support the assumption that UVA plays an important role in the development of CM. The variations in UVA (relevant to CM) and UVB (relevant to vitamin D production) over 1 day differ: the UVB : UVA ratio is maximal at noon. CONCLUSIONS: The best way to obtain a given dose of vitamin D with minimal carcinogenic risk is through a non-burning exposure in the middle of the day, rather than in the afternoon or morning. PMID- 26547143 TI - Divergence in DNA photorepair efficiency among genotypes from contrasting UV radiation environments in nature. AB - Populations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high-UVR habitat depended on the presence of visible and UV-A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR-caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high-UVR habitats repair DNA damage faster than genotypes from low-UVR habitats in the presence of visible and UV-A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV-A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR. PMID- 26547142 TI - Hearing in older adults with exfoliation syndrome/exfoliation glaucoma or primary open-angle glaucoma. AB - PURPOSE: To determine whether adults, aged 66-96 years, with exfoliation syndrome (XFS)/exfoliation glaucoma (XFG), or primary open-angle glaucoma (POAG) have poorer hearing than controls of similar age. METHODS: Case (XFS/XFG and POAG) and control status was diagnosed in the Reykjavik Glaucoma Studies (RGS) using slit lamp examination, visual field testing and optic disc photographs; the RGS data were merged with the Age, Gene/Environment Susceptibility-Reykjavik Study that collected hearing data using air-conduction, pure-tone thresholds obtained at 0.5, 1, 2, 3, 4, 6 and 8 kHz categorized by better ear and worse ear, based on pure-tone averages (PTAs) calculated separately for low and middle frequencies (PTA512 - mean of thresholds at 0.5, 1 and 2 kHz) and high frequencies (PTA3468 - mean of thresholds at 3, 4, 6 and 8 kHz). Multivariable linear regression was used to test for differences in PTAs between cases and controls. RESULTS: The mean age for 158 XFS/XFG cases (30.4% male) was 77.4 years, 95 POAG cases (35.8% male) was 77.9 years, and 123 controls (46.3% male) was 76.8 years. Using multivariable linear regression analysis, there were no consistent, statistically significant differences in PTAs between the two case groups and controls in either the low- or high-frequency range, even when stratified by age group. CONCLUSION: Among the older individuals examined in this study hearing loss is highly prevalent and strongly associated with male gender and increasing age. As we did not find consistent statistically significant difference in hearing between cases and controls the diagnosis of XFS/XFG or POAG does not as such routinely call for audiological evaluation. PMID- 26547145 TI - Building psychosocial assets and wellbeing among adolescent girls: A randomized controlled trial. AB - We conducted a randomized controlled trial of a 5-month resilience-based program (Girls First Resilience Curriculum or RC) among 2308 rural adolescent girls at 57 government schools in Bihar, India. Local women with at least a 10th grade education served as group facilitators. Girls receiving RC improved more (vs. controls) on emotional resilience, self-efficacy, social-emotional assets, psychological wellbeing, and social wellbeing. Effects were not detected on depression. There was a small, statistically significant negative effect on anxiety (though not likely clinically significant). Results suggest psychosocial assets and wellbeing can be improved for girls in high-poverty, rural schools through a brief school-day program. To our knowledge, this is one of the largest developing country trials of a resilience-based school-day curriculum for adolescents. PMID- 26547146 TI - Intergenerational transmission of ethnic identity and life satisfaction of Roma minority adolescents and their parents. AB - This study investigates intergeneration transmission of ethnic identity as a resource for life satisfaction of Roma adolescents and their parents. Historically, Roma represent the largest ethnic minority in Europe. They have been exposed to severe discrimination, social exclusion, and poverty. Therefore, identifying resources for their life satisfaction is theoretically and practically important. The present study included 1093 participants, of which there were 171 Roma adolescents (age: M = 14.96 years, SD = 1.85), 155 mothers (age: M = 36.16 years, SD = 5.77) and 123 fathers (age: M = 39.68 years, SD = 6.06). Further, a comparison group of 248 mainstream adolescents with their mothers (n = 221) and fathers (n = 175) was also included in the study. Adolescents and their parents provided data on ethnic identity (MEIM; Phinney, 1992) and life satisfaction (SWLS; Diener, Emmons, Larsen, & Griffin, 1985). Results indicated that Roma youth were lower on endorsement of ethnic identity and average on life satisfaction compared to their mainstream peers. A structural equation model showed that ethnic identity was a positive predictor of life satisfaction for both adolescents and their Roma parents. Furthermore, parents' ethnic identity was a predictor of adolescent life satisfaction. We concluded that for Roma youth and their parents, ethnic identity represents a salient source for life satisfaction and an intergenerational continuity of identity and life satisfaction exists. PMID- 26547144 TI - The Pillars of Hercules as a bathymetric barrier to gene flow promoting isolation in a global deep-sea shark (Centroscymnus coelolepis). AB - Knowledge of the mechanisms limiting connectivity and gene flow in deep-sea ecosystems is scarce, especially for deep-sea sharks. The Portuguese dogfish (Centroscymnus coelolepis) is a globally distributed and near threatened deep-sea shark. C. coelolepis population structure was studied using 11 nuclear microsatellite markers and a 497-bp fragment from the mtDNA control region. High levels of genetic homogeneity across the Atlantic (Phi(ST) = -0.0091, F(ST) = 0.0024, P > 0.05) were found suggesting one large population unit at this basin. The low levels of genetic divergence between Atlantic and Australia (Phi(ST) = 0.0744, P < 0.01; F(ST) = 0.0015, P > 0.05) further suggested that this species may be able to maintain some degree of genetic connectivity even across ocean basins. In contrast, sharks from the Mediterranean Sea exhibited marked genetic differentiation from all other localities studied (Phi(ST) = 0.3808, F(ST) = 0.1149, P < 0.001). This finding suggests that the shallow depth of the Strait of Gibraltar acts as a barrier to dispersal and that isolation and genetic drift may have had an important role shaping the Mediterranean shark population over time. Analyses of life history traits allowed the direct comparison among regions providing a complete characterization of this shark's populations. Sharks from the Mediterranean had markedly smaller adult body size and size at maturity compared to Atlantic and Pacific individuals. Together, these results suggest the existence of an isolated and unique population of C. coelolepis inhabiting the Mediterranean that most likely became separated from the Atlantic in the late Pleistocene. PMID- 26547147 TI - Requirement for vitamin D supplementation in patients using photoprotection: variations in vitamin D levels and bone formation markers. AB - BACKGROUND: Avoiding sun exposure is obligatory in photodermatoses; however, the need for oral supplementation with vitamin D appears unrecognized. The aim of the study was to investigate the seasonal variation of vitamin D level and bone formation markers in healthy individuals and to compare it with vitamin D status in patients using photoprotection. METHODS: Thirty-four healthy inhabitants of the Lodz region, Poland, a country in central Europe (51 degrees and 52 degrees north latitudes), were examined at the baseline visit within 2 weeks of peak sun exposure during recreational activity on vacation, after 8, and after 16 weeks. The group of patients using photoprotection comprised 104 patients with systemic lupus erythematosus. Serum 25(OH) vitamin D, procollagen type I N-terminal propeptide (PINP), and osteocalcin levels were measured. RESULTS: The serum 25 hydroxyvitamin D concentration was lower and vitamin D deficiency more common in patients using photoprotection than in healthy individuals during the warm and the cold season (P < 0.05). In healthy individuals, vitamin D deficiency was more prevalent after 8 and 16 weeks than at baseline assessment (P < 0.001). PINP level was 39.56 (30.51-53.22) ng/ml, and elevated in 50% of individuals, whereas osteocalcin was 18.88 (13.52-21.33) ng/ml, and within reference range. CONCLUSIONS: Diagnoses of vitamin D deficiency and oral supplementation in patients using photoprotection need to be included in practice. Peak 25 hydroxyvitamin D levels are probably achieved from vitamin D skin synthesis during the summertime and fall over time, starting from August. Elevated levels of PINP appear in line with the process of bone remodeling related to age. PMID- 26547148 TI - Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy. AB - Terahertz (THz) spectroscopy has turned out to be a powerful tool which is able to shed new light on the role of water in biomolecular processes. The low frequency spectrum of the solvated biomolecule in combination with MD simulations provides deep insights into the collective hydrogen bond dynamics on the sub-ps time scale. The absorption spectrum between 1 THz and 10 THz of solvated biomolecules is sensitive to changes in the fast fluctuations of the water network. Systematic studies on mutants of antifreeze proteins indicate a direct correlation between biological activity and a retardation of the (sub)-ps hydration dynamics at the protein binding site, i.e., a "hydration funnel." Kinetic THz absorption studies probe the temporal changes of THz absorption during a biological process, and give access to the kinetics of the coupled protein-hydration dynamics. When combined with simulations, the observed results can be explained in terms of a two-tier model involving a local binding and a long range influence on the hydration bond dynamics of the water around the binding site that highlights the significance of the changes in the hydration dynamics at recognition site for biomolecular recognition. Water is shown to assist molecular recognition processes. PMID- 26547149 TI - Communication: Exciton analysis in time-dependent density functional theory: How functionals shape excited-state characters. AB - Excited-state descriptors based on the one-particle transition density matrix referring to the exciton picture have been implemented for time-dependent density functional theory. State characters such as local, extended pipi(*), Rydberg, or charge transfer can be intuitively classified by simple comparison of these descriptors. Strong effects of the choice of the exchange-correlation kernel on the physical nature of excited states can be found and decomposed in detail leading to a new perspective on functional performance and the design of new functionals. PMID- 26547150 TI - Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure. AB - Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens. PMID- 26547151 TI - Communication: Entropic measure to prevent energy over-minimization in molecular dynamics simulations. AB - This work examines the impact of energy over-minimization on an ensemble of biological molecules subjected to the potential energy minimization procedure in vacuum. In the studied structures, long potential energy minimization stage leads to an increase of the main- and side-chain entropies in proteins. We show that such over-minimization may diverge the protein structures from the near-native attraction basin which possesses a minimum of free energy. We propose a measure based on the Pareto front of total entropy for quality assessment of minimized protein conformation. This measure may help in selection of adequate number of energy minimization steps in protein modelling and, thus, in preservation of the near-native protein conformation. PMID- 26547152 TI - Estimation and uncertainty of reversible Markov models. AB - Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software--http://pyemma.org--as of version 2.0. PMID- 26547153 TI - Biased diffusion in tubes of alternating diameter: Numerical study over a wide range of biasing force. AB - This paper is devoted to particle transport in a tube formed by alternating wide and narrow sections, in the presence of an external biasing force. The focus is on the effective transport coefficients--mobility and diffusivity, as functions of the biasing force and the geometric parameters of the tube. Dependences of the effective mobility and diffusivity on the tube geometric parameters are known in the limiting cases of no bias and strong bias. The approximations used to obtain these results are inapplicable at intermediate values of the biasing force. To bridge the two limits Brownian dynamics simulations were run to determine the transport coefficients at intermediate values of the force. The simulations were performed for a representative set of tube geometries over a wide range of the biasing force. They revealed that there is a range of the narrow section length, where the force dependence of the mobility has a maximum. In contrast, the diffusivity is a monotonically increasing function of the force. A simple formula is proposed, which reduces to the known dependences of the diffusivity on the tube geometric parameters in both limits of zero and strong bias. At intermediate values of the biasing force, the formula catches the diffusivity dependence on the narrow section length, if the radius of these sections is not too small. PMID- 26547154 TI - Reducing the cost of evaluating the committor by a fitting procedure. AB - Correct identification of reaction coordinates in complex systems is essential for understanding the mechanisms of their reaction dynamics. Existing methods for identifying reaction coordinates typically require knowledge of the committor- the probability of a given configuration to reach the product basin. The high computational cost of evaluating committors has limited applications of methods for identifying reaction coordinates. We proposed a fitting procedure that can reduce the cost of evaluating committors by an order of magnitude or more. The method only requires evaluating the committors of a few configurations in a transition path by the standard and costly shooting procedure. The committors of the other configurations are then estimated with great accuracy by a sigmoid function derived from fitting the few numerically evaluated committors. The method has been systematically tested on a model system of a Brownian particle moving in a one-dimensional double-well potential, and a small biomolecular system--the isomerization of alanine dipeptide in vacuum and in explicit water. PMID- 26547155 TI - An efficient and stable hybrid extended Lagrangian/self-consistent field scheme for solving classical mutual induction. AB - We have adapted a hybrid extended Lagrangian self-consistent field (EL/SCF) approach, developed for time reversible Born Oppenheimer molecular dynamics for quantum electronic degrees of freedom, to the problem of classical polarization. In this context, the initial guess for the mutual induction calculation is treated by auxiliary induced dipole variables evolved via a time-reversible velocity Verlet scheme. However, we find numerical instability, which is manifested as an accumulation in the auxiliary velocity variables, that in turn results in an unacceptable increase in the number of SCF cycles to meet even loose convergence tolerances for the real induced dipoles over the course of a 1 ns trajectory of the AMOEBA14 water model. By diagnosing the numerical instability as a problem of resonances that corrupt the dynamics, we introduce a simple thermostating scheme, illustrated using Berendsen weak coupling and Nose Hoover chain thermostats, applied to the auxiliary dipole velocities. We find that the inertial EL/SCF (iEL/SCF) method provides superior energy conservation with less stringent convergence thresholds and a correspondingly small number of SCF cycles, to reproduce all properties of the polarization model in the NVT and NVE ensembles accurately. Our iEL/SCF approach is a clear improvement over standard SCF approaches to classical mutual induction calculations and would be worth investigating for application to ab initio molecular dynamics as well. PMID- 26547156 TI - Hohenberg-Kohn theorems in electrostatic and uniform magnetostatic fields. AB - The Hohenberg-Kohn (HK) theorems of bijectivity between the external scalar potential and the gauge invariant nondegenerate ground state density, and the consequent Euler variational principle for the density, are proved for arbitrary electrostatic field and the constraint of fixed electron number. The HK theorems are generalized for spinless electrons to the added presence of an external uniform magnetostatic field by introducing the new constraint of fixed canonical orbital angular momentum. Thereby, a bijective relationship between the external scalar and vector potentials, and the gauge invariant nondegenerate ground state density and physical current density, is proved. A corresponding Euler variational principle in terms of these densities is also developed. These theorems are further generalized to electrons with spin by imposing the added constraint of fixed canonical orbital and spin angular momenta. The proofs differ from the original HK proof and explicitly account for the many-to-one relationship between the potentials and the nondegenerate ground state wave function. A Percus-Levy-Lieb constrained-search proof expanding the domain of validity to N-representable functions, and to degenerate states, again for fixed electron number and angular momentum, is also provided. PMID- 26547157 TI - Image effects in transport at metal-molecule interfaces. AB - We present a method for incorporating image-charge effects into the description of charge transport through molecular devices. A simple model allows us to calculate the adjustment of the transport levels, due to the polarization of the electrodes as charge is added to and removed from the molecule. For this, we use the charge distributions of the molecule between two metal electrodes in several charge states, rather than in gas phase, as obtained from a density-functional theory-based transport code. This enables us to efficiently model level shifts and gap renormalization caused by image-charge effects, which are essential for understanding molecular transport experiments. We apply the method to benzene di amine molecules and compare our results with the standard approach based on gas phase charges. Finally, we give a detailed account of the application of our approach to porphyrin-derivative devices recently studied experimentally by Perrin et al. [Nat. Nanotechnol. 8, 282 (2013)], which demonstrates the importance of accounting for image-charge effects when modeling transport through molecular junctions. PMID- 26547158 TI - Fitting high-dimensional potential energy surface using active subspace and tensor train (AS+TT) method. AB - This paper is the first application of the tensor-train (TT) cross approximation procedure for potential energy surface fitting. In order to reduce the complexity, we combine the TT-approach with another technique recently introduced in the field of numerical analysis: an affine transformation of Cartesian coordinates into the active subspaces where the PES function has the most variability. The numerical experiments for the water molecule and for the nitrous acid molecule confirm the efficiency of this approach. PMID- 26547159 TI - Quantum power functional theory for many-body dynamics. AB - We construct a one-body variational theory for the time evolution of nonrelativistic quantum many-body systems. The position- and time-dependent one body density, particle current, and time derivative of the current act as three variational fields. The generating (power rate) functional is minimized by the true current time derivative. The corresponding Euler-Lagrange equation, together with the continuity equation for the density, forms a closed set of one-body equations of motion. Space- and time-nonlocal one-body forces are generated by the superadiabatic contribution to the functional. The theory applies to many electron systems. PMID- 26547160 TI - A general method for molecular modeling of nucleation from the melt. AB - Crystallization is one of the fundamental phase transition processes, and it is also important practically, for example, in the chemical, food, and pharmaceutical industries. Despite its importance, however, our basic understanding of crystallization, and especially crystal nucleation, at the molecular level is still incomplete. In this work, we present a general molecular simulation approach that can be used to investigate the nucleation of crystals from a subcooled liquid. Our method combines a previously proposed general method to construct structure-based order parameters [E. E. Santiso and B. L. Trout, J. Chem. Phys. 134, 064109 (2011)] with the string method in collective variables [L. Maragliano et al., J. Chem. Phys. 125, 024106 (2006)] to obtain a minimum free energy path connecting the liquid and solid basins. We then use Markovian milestoning with Voronoi tessellations [E. Vanden-Eijnden and M. Venturoli, J. Chem. Phys. 130, 194101 (2009); L. Maragliano et al., J. Chem. Theory Comput. 5, 2589-2594 (2009)] to obtain the free energy profile along the path and the nucleation kinetics. We illustrate the application of this method to the nucleation of Benzene-I crystals from the melt, and compare the results to those previously found using transition path sampling [M. Shah et al., J. Phys. Chem. B 115, 10400-10412 (2011)]. PMID- 26547161 TI - Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase. AB - In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene. PMID- 26547162 TI - Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations. AB - The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r(-1) term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed phase simulations of chemical reactions. PMID- 26547163 TI - Distributed replica dynamics. AB - A distributed replica dynamics (DRD) method is proposed to calculate rare-event molecular dynamics using distributed computational resources. Similar to Voter's parallel replica dynamics (PRD) method, the dynamics of independent replicas of the system are calculated on different computational clients. In DRD, each replica runs molecular dynamics from an initial state for a fixed simulation time and then reports information about the trajectory back to the server. A simulation clock on the server accumulates the simulation time of each replica until one reports a transition to a new state. Subsequent calculations are initiated from within this new state and the process is repeated to follow the state-to-state evolution of the system. DRD is designed to work with asynchronous and distributed computing resources in which the clients may not be able to communicate with each other. Additionally, clients can be added or removed from the simulation at any point in the calculation. Even with heterogeneous computing clients, we prove that the DRD method reproduces the correct probability distribution of escape times. We also show this correspondence numerically; molecular dynamics simulations of Al(100) adatom diffusion using PRD and DRD give consistent exponential distributions of escape times. Finally, we discuss guidelines for choosing the optimal number of replicas and replica trajectory length for the DRD method. PMID- 26547164 TI - Heavy rare-gas atomic pairs and the "double penalty" issue: Isotropic Raman lineshapes by Kr2, Xe2, and KrXe at room temperature. AB - We report absolutely calibrated isotropic Raman lineshapes for Kr2 and Xe2 and for KrXe at 294.5 K and compare them to quantum-mechanically generated lineshapes by using state-of-the-art second-order Moller-Plesset and DFT/B3LYP data sets for the induced mean dipole polarizability ?. A very good agreement between the numerical and the experimental data was observed but the large uncertainty margins and the short Raman frequency interval probed in our experiment prevented us from rating on a more refined scale the performance of the tested ? models. These drawbacks are inherent in isotropic Raman spectrum measurements and amplified for dissimilar pairs because, for such systems and spectra, the unreliable operation of subtracting optical signals of comparable magnitude occurs twice per Raman frequency shift value, thus penalizing twice the quality of the measured data. In light of our findings and of previously reported evidence about related electric properties in Kr2 and Xe2 and in KrXe, we are left with no doubt as to the consistency of the induced-polarizability and interatomic-potential data used for these three systems at the reported level of accuracy. PMID- 26547165 TI - Intriguing structures and magic sizes of heavy noble metal nanoclusters around size 55 governed by relativistic effect and covalent bonding. AB - Nanoclusters usually display exotic physical and chemical properties due to their intriguing geometric structures in contrast to their bulk counterparts. By means of first-principles calculations within density functional theory, we find that heavy noble metal PtN nanoclusters around the size N = 55 begin to prefer an open configuration, rather than previously reported close-packed icosahedron or core shell structures. Particularly, for PtN, the widely supposed icosahedronal magic cluster is changed to a three-atomic-layered structure with D6h symmetry, which can be well addressed by our recently established generalized Wulff construction principle (GWCP). However, the magic number of PtN clusters around 55 is shifted to a new odd number of 57. The high symmetric three-layered Pt57 motif is mainly stabilized by the enhanced covalent bonding contributed by both spin-orbital coupling effect and the open d orbital (5d(9)6s(1)) of Pt, which result in a delicate balance between the enhanced Pt-Pt covalent bonding of the interlayers and negligible d dangling bonds on the cluster edges. These findings about PtN clusters are also applicable to IrN clusters, but qualitatively different from their earlier neighboring element Os and their later neighboring element Au. The magic numbers for Os and Au are even, being 56 and 58, respectively. The findings of the new odd magic number 57 are the important supplementary of the recently established GWCP. PMID- 26547166 TI - Ab initio theory for femtosecond spin dynamics, angle-resolved fidelity analysis, and the magneto-optical Kerr effect in the Ni3(CH3OH) and Co3(+)(CH3OH) clusters. AB - We present a systematic analysis of the ab initio controlled femtosecond spin dynamics in Ni3(CH3OH) and Co3(+)(CH3OH) clusters achieved by a spin-orbit coupling enabled Lambda process. The distortion caused by the attachment of CH3OH to one of the active magnetic centers of the Ni3 and the Co3(+) clusters induces asymmetric geometries which result in well localized spin densities on the magnetic centers. With the use of high-level quantum chemistry methods, successful spin-flip scenarios are demonstrated for both clusters. In order to assess the experimental accessibility of those effects, we compute their tolerance with respect to two laser pulse parameters, i.e., the energy detuning as well as the deviation of the polar angle phi from its optimized value. Finally, we calculate the magneto-optical Kerr effect in order to connect to the susceptibility tensor chi as an experimentally measurable quantity. PMID- 26547167 TI - Laser spectroscopy of the A(2)Sigma(+)-X(2)Pii band system of l-SiC3H. AB - The A(2)Sigma(+)-X(2)Pii band system of l-SiC3H in the region 14,700-16,300 cm( 1) was re-investigated by laser induced fluorescence (LIF) and fluorescence depletion spectroscopy. Rotational analyses were made for three intense bands 0(0)(0), 4(0)(1), and 6(0)(1)7(0)(1) by observing high-resolution LIF excitation spectra. The determined rotational constants demonstrate that SiC3H is linear in the A state, as is the case in the X state, and the observed band types are consistent with the vibrational assignments. The nu3(") (C1-C2 stretch) level was identified in a newly observed dispersed fluorescence spectrum from the zero vibrational level of the A state. PMID- 26547168 TI - Photoelectron spectroscopic and computational study of (M-CO2)(-) anions, M = Cu, Ag, Au. AB - In a combined photoelectron spectroscopic and computational study of (M-CO2)(-), M = Au, Ag, Cu, anionic complexes, we show that (Au-CO2)(-) forms both the chemisorbed and physisorbed isomers, AuCO2(-) and Au(-)(CO2), respectively; that (Ag-CO2)(-) forms only the physisorbed isomer, Ag(-)(CO2); and that (Cu-CO2)(-) forms only the chemisorbed isomer, CuCO2(-). The two chemisorbed complexes, AuCO2(-) and CuCO2(-), are covalently bound, formate-like anions, in which their CO2 moieties are significantly reduced. These two species are examples of electron-induced CO2 activation. The two physisorbed complexes, Au(-)(CO2) and Ag(-)(CO2), are electrostatically and thus weakly bound. PMID- 26547169 TI - Heat- and light-induced transformations of Yb trapping sites in an Ar matrix. AB - The low-lying electronic states of Yb isolated in a solid Ar matrix grown at 4.2 K are characterized through absorption and emission spectroscopy. Yb atoms are found to occupy three distinct thermally stable trapping sites labeled "red," "blue," and "violet" according to the relative positions of the absorption features they produce. Classical simulations of the site structure and relative stability broadly reproduced the experimentally observed matrix-induced frequency shifts and thus identified the red, blue, and violet sites as due to respective single substitutional (ss), tetravacancy (Tv), and hexavacancy (Hv) occupation. Prolonged excitation of the (1)S -> (1)P transition was found to transfer the Yb population from hv sites into Tv and ss sites. The process showed reversibility in that annealing to 24 K predominantly transferred the Tv population back into Hv sites. Population kinetics were used to deduce the effective rate parameters for the site transformation processes. Experimental observations indicate that the blue and violet sites lie close in energy, whereas the red one is much less stable. Classical simulations identify the blue site as the most stable one. PMID- 26547170 TI - Role of excited state solvent fluctuations on time-dependent fluorescence Stokes shift. AB - We explore the connection between the solvation dynamics of a chromophore upon photon excitation and equilibrium fluctuations of the solvent. Using molecular dynamics simulations, fluorescence Stokes shift for the tryptophan in Staphylococcus nuclease was examined using both nonequilibrium calculations and linear response theory. When the perturbed and unperturbed surfaces exhibit different solvent equilibrium fluctuations, the linear response approach on the former surface shows agreement with the nonequilibrium process. This agreement is excellent when the perturbed surface exhibits Gaussian statistics and qualitative in the case of an isomerization induced non-Gaussian statistics. However, the linear response theory on the unperturbed surface breaks down even in the presence of Gaussian fluctuations. Experiments also provide evidence of the connection between the excited state solvent fluctuations and the total fluorescence shift. These observations indicate that the equilibrium statistics on the excited state surface characterize the relaxation dynamics of the fluorescence Stokes shift. Our studies specifically analyze the Gaussian fluctuations of the solvent in the complex protein environment and further confirm the role of solvent fluctuations on the excited state surface. The results are consistent with previous investigations, found in the literature, of solutes dissolved in liquids. PMID- 26547171 TI - A classical force field for tetrahedral oxyanions developed using hydration properties: The examples of pertechnetate (TcO4(-)) and sulfate (SO4(2-)). AB - Radioactive pertechnetate, (99)TcO4(-), is one of the most problematic ionic species in the context of the clean up and storage of nuclear waste. Molecular simulations can be used to understand the behavior of TcO4(-) in dilute aqueous solutions, providing reliable potentials are available. This work outlines the development of a new potential model for TcO4(-) and competing SO4(2-), optimized using their hydration properties, such as the Gibbs hydration free energy (calculated using Bennett's acceptance ratio method). The findings show that the TcO4(-) oxyanion has a very low hydration free energy (-202 kJ mol(-1)) compared to other anions (Cl(-), I(-), SO4(2-)) leading to fast water exchange dynamics and explaining its observed high mobility in the aqueous environment. Its hydrated structure, investigated using ion-water radial distribution functions, shows that it is unique amongst the other anions in that it does not possess well defined hydration shells. Since contaminants and ubiquitous species in the aqueous environment are often present as tetrahedral oxyanions, it is proposed that the approach could easily be extended to a whole host of other species. PMID- 26547172 TI - Isotopic Soret effect in ternary mixtures: Theoretical predictions and molecular simulations. AB - In this paper, we study the Soret effect in ternary fluid mixtures of isotopic argon like atoms. Soret coefficients have been computed using non-equilibrium molecular dynamics and a theoretical approach based on our extended Prigogine model (with mass effect) and generalized to mixtures with any number of components. As is well known for binary mixture studies, the heaviest component always accumulates on the cold side whereas the lightest species accumulate on the hot side. An interesting behavior is observed for the species with the intermediate mass: it can accumulate on both sides, depending on composition and mass ratios. A simple picture can be given to understand this change of sign: the intermediate mass species can be seen as evolving in an equivalent fluid whose species mass varies with composition. An excellent prediction of all simulated data has been obtained using our model including the change of sign of the Soret coefficient for species with intermediate mass. PMID- 26547173 TI - Unraveling the success and failure of mode coupling theory from consideration of entropy. AB - We analyze the dynamics of model supercooled liquids in a temperature regime where predictions of mode coupling theory (MCT) are known to be valid qualitatively. In this regime, the Adam-Gibbs (AG) relation, based on an activation picture of dynamics, also describes the dynamics satisfactorily, and we explore the mutual consistency and interrelation of these descriptions. Although entropy and dynamics are related via phenomenological theories, the connection between MCT and entropy has not been argued for. In this work, we explore this connection and provide a microscopic derivation of the phenomenological Rosenfeld theory. At low temperatures, the overlap between the MCT power law regime and AG relation implies that the AG relation predicts an avoided divergence at Tc, the origin of which can be related to the vanishing of pair configurational entropy, which we find occurring at the same temperature. We also show that the residual multiparticle entropy plays an important role in describing the relaxation time. PMID- 26547174 TI - Non-equilibrium theory of arrested spinodal decomposition. AB - The non-equilibrium self-consistent generalized Langevin equation theory of irreversible relaxation [P. E. Ramrez-Gonzalez and M. Medina-Noyola, Phys. Rev. E 82, 061503 (2010); 82, 061504 (2010)] is applied to the description of the non equilibrium processes involved in the spinodal decomposition of suddenly and deeply quenched simple liquids. For model liquids with hard-sphere plus attractive (Yukawa or square well) pair potential, the theory predicts that the spinodal curve, besides being the threshold of the thermodynamic stability of homogeneous states, is also the borderline between the regions of ergodic and non ergodic homogeneous states. It also predicts that the high-density liquid-glass transition line, whose high-temperature limit corresponds to the well-known hard sphere glass transition, at lower temperature intersects the spinodal curve and continues inside the spinodal region as a glass-glass transition line. Within the region bounded from below by this low-temperature glass-glass transition and from above by the spinodal dynamic arrest line, we can recognize two distinct domains with qualitatively different temperature dependence of various physical properties. We interpret these two domains as corresponding to full gas-liquid phase separation conditions and to the formation of physical gels by arrested spinodal decomposition. The resulting theoretical scenario is consistent with the corresponding experimental observations in a specific colloidal model system. PMID- 26547175 TI - Ab initio calculations of many-body interactions for compressed solid argon. AB - An investigation on many-body effects of solid argon at high pressure was conducted based on a many-body expansion of interaction energy. The three- and four-body terms in the expansion were calculated using the coupled-cluster method with single, double, and noniterative triple theory and incremental method, in which the configurations of argon trimers and tetramers were chosen as the same as those in the actual lattice. The four-body interactions in compressed solid argon were estimated for the first time, and the three-body interaction ab initio calculations were extended to a small distance. It shows that the four-body contribution is repulsive at high densities and effectively cancels the three body lattice energy. The dimer potential plus three-body interaction can well reproduce the measurements of equation of state at pressure approximately lower than ~60 GPa, when including the four-body effects extends the agreement up to the maximum experimental pressure of 114 GPa. PMID- 26547176 TI - Structure of a zinc oxide ultra-thin film on Rh(100). AB - The structural parameters of ultra-thin zinc oxide films on Rh(100) are investigated using low-energy electron diffraction intensity (LEED I-V) curves, scanning tunneling microscopy (STM), and first-principles density functional theory (DFT) calculations. From the analysis of LEED I-V curves and DFT calculations, two optimized models A and B are determined. Their structures are basically similar to the planer h-BN ZnO(0001) structure, although some oxygen atoms protrude from the surface, associated with an in-plane shift of Zn atoms. From a comparison of experimental STM images and simulated STM images, majority and minority structures observed in the STM images represent the two optimized models A and B, respectively. PMID- 26547177 TI - Interfacial friction based quasi-continuum hydrodynamical model for nanofluidic transport of water. AB - In this work, we formulate a one-dimensional isothermal hydrodynamic transport model for water, which is an extension to our recently proposed hydrodynamic model for Lennard-Jones type fluid [R. Bhadauria and N. R. Aluru, J. Chem. Phys. 139, 074109 (2013)]. Viscosity variations in confinement are incorporated by the local average density method. Dirichlet boundary conditions are provided in the form of slip velocity that depends upon the macroscopic interfacial friction coefficient. The value of this friction coefficient is computed using a novel generalized Langevin equation formulation that eliminates the use of equilibrium molecular dynamics simulation. Gravity driven flows of SPC/E water confined between graphene and silicon slit shaped nanochannels are considered as examples for low and high friction cases. The proposed model yields good quantitative agreement with the velocity profiles obtained from non-equilibrium molecular dynamics simulations. PMID- 26547178 TI - The application of inelastic neutron scattering to explore the significance of a magnetic transition in an iron based Fischer-Tropsch catalyst that is active for the hydrogenation of CO. AB - An iron based Fischer-Tropsch synthesis catalyst is evaluated using CO hydrogenation at ambient pressure as a test reaction and is characterised by a combination of inelastic neutron scattering (INS), powder X-ray diffraction, temperature-programmed oxidation, Raman scattering, and transmission electron microscopy. The INS spectrum of the as-prepared bulk iron oxide pre-catalyst (hematite, alpha-Fe2O3) is distinguished by a relatively intense band at 810 cm( 1), which has previously been tentatively assigned as a magnon (spinon) feature. An analysis of the neutron scattering intensity of this band as a function of momentum transfer unambiguously confirms this assignment. Post-reaction, the spinon feature disappears and the INS spectrum is characterised by the presence of a hydrocarbonaceous overlayer. A role for the application of INS in magnetic characterisation of iron based FTS catalysts is briefly considered. PMID- 26547179 TI - Adenine adlayers on Cu(111): XPS and NEXAFS study. AB - The adsorption of adenine on Cu(111) was studied by photoelectron and near edge x ray absorption fine structure spectroscopy. Disordered molecular films were deposited by means of physical vapor deposition on the substrate at room temperature. Adenine chemisorbs on the Cu(111) surface with strong rehybridization of the molecular orbitals and the Cu 3d states. Annealing at 150 degrees C caused the desorption of weakly bonded molecules accompanied by formation of a short-range ordered molecular adlayer. The interface is characterized by the formation of new states in the valence band at 1.5, 7, and 9 eV. The present work complements and refines existing knowledge of adenine interaction with this surface. The coverage is not the main parameter that defines the adenine geometry and adsorption properties on Cu(111). Excess thermal energy can further rearrange the molecular adlayer and, independent of the initial coverage, the flat lying stable molecular adlayer is formed. PMID- 26547180 TI - Extension, torque, and supercoiling in single, stretched, and twisted DNA molecules. AB - We reinvestigate the model originally studied by Neukirch and Marko that describes the extension, torque, and supercoiling in single, stretched, and twisted DNA molecules, which consists of a mixture of extended state and supercoiled state, using now a more accurate form of the free energy for the untwisted but stretched DNA. The original model uses an approximate form of this free energy and the agreement with experiment is only qualitative. We find that this more accurate free energy significantly improves the results, which bring them into quantitative agreement with experiment, throughout the entire force regime. This is rather surprising, considering that the theory is completely parameter-free. PMID- 26547181 TI - DNA terminal base pairs have weaker hydrogen bonds especially for AT under low salt concentration. AB - DNA base pairs are known to open more easily at the helix terminal, a process usually called end fraying, the details of which are still poorly understood. Here, we present a mesoscopic model calculation based on available experimental data where we consider separately the terminal base pairs of a DNA duplex. Our results show an important reduction of hydrogen bond strength for terminal cytosine-guanine (CG) base pairs which is uniform over the whole range of salt concentrations, while for AT base pairs, we obtain a nearly 1/3 reduction but only at low salt concentrations. At higher salt concentrations, terminal adenine thymine (AT) pair has almost the same hydrogen bond strength than interior bases. The calculated terminal stacking interaction parameters display some peculiarly contrasting behavior. While there is mostly no perceptible difference to internal stacking, for some cases, we observe an unusually strong dependence with salt concentration which does not appear follow any pattern or trend. PMID- 26547182 TI - Equilibrium simulation of trp-cage in the presence of protein crowders. AB - While steric crowders tend to stabilize globular proteins, it has been found that protein crowders can have an either stabilizing or destabilizing effect, where a destabilization may arise from nonspecific attractive interactions between the test protein and the crowders. Here, we use Monte Carlo replica-exchange methods to explore the equilibrium behavior of the miniprotein trp-cage in the presence of protein crowders. Our results suggest that the surrounding crowders prevent trp-cage from adopting its global native fold, while giving rise to a stabilization of its main secondary-structure element, an alpha-helix. With the crowding agent used (bovine pancreatic trypsin inhibitor), the trp-cage-crowder interactions are found to be specific, involving a few key residues, most of which are prolines. The effects of these crowders are contrasted with those of hard-sphere crowders. PMID- 26547183 TI - Short-time dynamics of 2-thiouracil in the light absorbing S2(pipi(*)) state. AB - Ultrahigh quantum yields of intersystem crossing to the lowest triplet state T1 are observed for 2-thiouracils (2TU), which is in contrast to the natural uracils that predominantly exhibit ultrafast internal conversion to the ground state upon excitation to the singlet excited state. The intersystem crossing mechanism of 2TU has recently been investigated using second-order perturbation methods with a high-level complete-active space self-consistent field. Three competitive nonadiabatic pathways to the lowest triplet state T1 from the initially populated singlet excited state S2 were proposed. We investigate the initial decay dynamics of 2TU from the light absorbing excited states using resonance Raman spectroscopy, time-dependent wave-packet theory in the simple model, and complete active space self-consistent field (CASSCF) and time dependent-Becke's three parameter exchange and correlation functional with the Lee-Yang-Parr correlation functional (TD-B3LYP) calculations. The obtained short-time structural dynamics in easy-to-visualize internal coordinates were compared with the CASSCF(16,11) predicted key nonadiabatic decay routes. Our results indicate that the predominant decay pathway initiated at the Franck-Condon region is toward the S2/S1 conical intersection point and S2T3 intersystem crossing point, but not toward the S2T2 intersystem crossing point. PMID- 26547184 TI - Comment on "Analyses of bifurcation of reaction pathways on a global reaction route map: A case study of gold cluster Au5" [J. Chem. Phys. 143, 014301 (2015)]. AB - We demonstrate by an example that the search for valley-ridge transition (VRT) points used in the commented paper does not always indicate a bifurcation of a reaction path. This was claimed. PMID- 26547185 TI - Response to "Comment on 'Analyses of bifurcation of reaction pathways on a global reaction route map: A case study of gold cluster Au5"' [J. Chem. Phys. 143, 177101 (2015)]. AB - The existence of a valley-ridge transition (VRT) point along the intrinsic reaction coordinate does not always indicate the existence of two minima in the product side, but VRT is a sign of bifurcating nature of dynamical trajectories running on the potential energy surface. It is demonstrated by molecular dynamics simulations. PMID- 26547186 TI - Erratum: "Quantum dynamical simulation of the scattering of Ar from a frozen LiF(100) surface based on a first principles interaction potential" [J. Chem. Phys. 143, 014705 (2015)]. PMID- 26547187 TI - Publisher's Note: "Transition state ensemble optimization for reactions of arbitrary complexity" [J. Chem. Phys. 143, 134111 (2015)]. PMID- 26547188 TI - Helical intensity-modulated radiotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate--first results of the PLATIN 1 trial. AB - BACKGROUND: Definitive, percutaneous irradiation of the prostate and the pelvic lymph nodes in high-risk prostate cancer is the alternative to prostatectomy plus lymphadenectomy. To date, the role of whole pelvis radiotherapy (WPRT) has not been clarified especially taking into consideration the benefits of high conformal IMRT (intensity modulated radiotherapy) of complex-shaped target volumes. METHODS: From 2009 to 2012, 40 patients of high-risk prostate cancer with an increased risk of microscopic lymph node involvement were enrolled into this prospective phase II trial. Patients received at least two months of antihormonal treatment (AT) before radiotherapy continuing for at least 2 years. Helical IMRT (tomotherapy) of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated, moderate hypofractionated boost (single dose of 2.25 Gy) to the prostate (76.5 Gy) was performed in 34 fractions. PSA levels, prostate related symptoms and quality of life were assessed at regular intervals for 24 months. RESULTS: Of the 40 patients enrolled, 38 finished the treatment as planned. Overall acute toxicity rates were low and no acute grade 3 or 4 gastrointestinal (GI) and genitourinary (GU) toxicity occurred. 21.6% of patients experienced acute grade 2 but no late grade >= 2 GI toxicity. Regarding GU side effects, results showed 48.6% acute grade 2 and 6.4% late grade 2 toxicity. After a median observation time of 23.4 months the PLATIN 1 trial can be considered as sufficiently safe meeting the prospectively defined aims of the trial. With 34/37 patients free of a PSA recurrence it shows promising efficacy. CONCLUSION: Tomotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate can be performed safely and without excessive toxicity. The combined irradiation of both prostate and pelvic lymph nodes seems to be as well tolerated as the irradiation of the prostate alone. TRIAL REGISTRATION: Trial Numbers: ARO 2009-05, ClinicalTrials.gov: NCT01903408. PMID- 26547189 TI - Plasmonic SERS biosensing nanochips for DNA detection. AB - The development of rapid, cost-effective DNA detection methods for molecular diagnostics at the point-of-care (POC) has been receiving increasing interest. This article reviews several DNA detection techniques based on plasmonic-active nanochip platforms developed in our laboratory over the last 5 years, including the molecular sentinel-on-chip (MSC), the multiplex MSC, and the inverse molecular sentinel-on-chip (iMS-on-Chip). DNA probes were used as the recognition elements, and surface-enhanced Raman scattering (SERS) was used as the signal detection method. Sensing mechanisms were based on hybridization of target sequences and DNA probes, resulting in a distance change between SERS reporters and the nanochip's plasmonic-active surface. As the field intensity of the surface plasmon decays exponentially as a function of distance, the distance change in turn affects SERS signal intensity, thus indicating the presence and capture of the target sequences. Our techniques were single-step DNA detection techniques. Target sequences were detected by simple delivery of sample solutions onto DNA probe-functionalized nanochips and measuring the SERS signal after appropriate incubation times. Target sequence labeling or washing to remove unreacted components was not required, making the techniques simple, easy-to-use, and cost-effective. The usefulness of the nanochip platform-based techniques for medical diagnostics was illustrated by the detection of host genetic biomarkers for respiratory viral infection and of the dengue virus gene. PMID- 26547190 TI - Identification of trace levels of selenomethionine and related organic selenium species in high-ionic-strength waters. AB - A new anion-exchange chromatographic separation method was used for the simultaneous speciation analysis of selenoamino acids and the more ubiquitous inorganic selenium oxyanions, selenite and selenate. For quantification, this separation was coupled to inductively coupled plasma-mass spectrometry to achieve an instrumental detection limit of 5 ng Se L(-1) for all species. This chromatographic method was also coupled to electrospray tandem mass spectrometry to observe the negative ion mode fragmentation of selenomethionine and one of its oxidation products. Low detection limits were achieved, which were similar to those obtained using inductively coupled plasma-mass spectrometry. An extensive preconcentration and cleanup procedure using cation-exchange solid-phase extraction was developed for the identification and quantification of trace levels of selenomethionine in environmental samples. Preconcentration factors of up to five were observed for selenomethionine, which in addition to the removal of high concentrations of sulphate and chloride from industrial process waters, allowed for an unambiguous analysis that would have been impossible otherwise. Following these methods, selenomethionine was identified at an original concentration of 3.2 ng Se L(-1) in samples of effluent collected at a coal-fired power plant's biological remediation site. It is the first time that this species has been identified in the environment, outside of a biological entity. Additionally, oxidation products of selenomethionine were identified in river water and laboratory algal culture samples. High-resolution mass spectrometry was employed to postulate the chemical structures of these species. PMID- 26547191 TI - A novel reverse fluorescent immunoassay approach for sensing human chorionic gonadotropin based on silver-gold nano-alloy and magnetic nanoparticles. AB - A novel and environmentally friendly reverse fluorescent immunoassay approach was proposed and utilized for sensing human chorionic gonadotropin (HCG) in human serum by coupling a newly prepared and highly fluorescent glutathione-stabilized silver-gold nano-alloy (GSH-AgAuNAs) with magnetic nanoparticles (MNPs). To construct such a reverse system, fluorescent GSH-AgAuNAs and MNPs were first prepared and bio-functionalized with monoclonal antibodies (Mab-I and Mab-II) toward HCG antigen, respectively. Then, the GSH-AgAuNAs functionalized with Mab-I were incubated with HCG, followed by the addition of MNPs attached to Mab-II. Thereafter, a sandwich-type immunoassay could be constructed for determination of HCG owing to the antibody-antigen recognition between the functionalized GSH AgAuNAs and MNPs. Afterwards, a magnetic collection was employed. Hence, the amount of GSH-AgAuNAs would be reduced through an immuno-magnetic separation, thus weakening the fluorescent intensity. Different from conventional immunoassay, our work determined the quantitative signal by measuring the decreasing gradient fluorescent intensity. Under optimal conditions, the developed reverse method exhibited a wide linear range of 0.5-600 ng mL(-1) toward HCG with a detection limit of 0.25 ng mL(-1). Additionally, the proposed immunoassay was validated using spiked samples, illustrating a satisfactory result in practical application. PMID- 26547192 TI - Incidence of Pneumonia After Videofluoroscopic Swallowing Study and Associated Factors. AB - Pneumonia after videofluoroscopic swallow study (VFSS) is sometimes considered to be caused by aspiration during VFSS; however, to our knowledge, a relationship between these events has not been clearly investigated. The aim of this study was to assess the incidence of VFSS-related pneumonia and related factors. Overall, 696 VFSS cases were retrospectively reviewed. Cases in which blood culture was performed within 3 days after VFSS due to newly developed infectious signs were considered as post-VFSS infection cases. Pneumonia was suspected when there was some evidence of respiratory infectious signs in clinical, radiological, and laboratory findings. The underlying disease, clinical signs, and VFSS findings of the pneumonia group were assessed. Among 696 cases, pneumonia was diagnosed in 15 patients. The patients in the pneumonia group tended to be older and had higher aspiration rate on VFSS than those in the non-pneumonia group. In the pneumonia group, 2 patients showed no aspiration during VFSS. In 6 patients, pneumonia developed after massive aspiration of gastric content in 5 patients and inappropriate oral feeding with risk of aspiration before VFSS in 1 patient. Only 7 patients (1.0 %) were finally determined as having VFSS-related pneumonia. In conclusion, the 72-h incidence of VFSS-related pneumonia was 1.0 %. Old age and severity of swallowing difficulty are associated with occurrence of pneumonia. PMID- 26547193 TI - An analysis of national collaboration with Spanish researchers abroad in the health sciences. AB - BACKGROUND: The establishment of scientific collaborations with researchers abroad can be considered a good practice to make appropriate use of their knowledge and to increase the possibilities of them returning to their country. This paper analyses the collaboration between Spanish researchers abroad devoted to health sciences and national science institutions. METHODS: We used the Fontes' approach to perform a study on this collaboration with Spanish researchers abroad. We measured the level of national and international cooperation, the opportunity provided by the host country to collaborate, the promotion of collaboration by national science institutions, and the types of collaboration. A total of 88 biomedical researchers out of the 268 Spanish scientists who filled up the survey participated in the study. Different data analyses were performed to study the variables selected to measure the scientific collaboration and profile of Spanish researchers abroad. RESULTS: There is a high level of cooperation between Spanish health science researchers abroad and international institutions, which contrasts with the small-scale collaboration with national institutions. Host countries facilitate this collaboration with national and international scientific institutions to a larger extent than the level of collaboration promotion carried out by Spanish institutions. CONCLUSIONS: The national collaboration with Spanish researchers abroad in the health sciences is limited. Thus, the practice of making appropriate use of the potential of their expertise should be promoted and the opportunities for Spanish health science researchers to return home should be improved. PMID- 26547194 TI - Enhanced expression of SaHMA3 plays critical roles in Cd hyperaccumulation and hypertolerance in Cd hyperaccumulator Sedum alfredii Hance. AB - MAIN CONCLUSION: The enhanced expression of a P 1B -type ATPase gene ( SaHMA3 ) is essential for Cd hyperaccumulation and hypertolerance in Sedum alfredii Hance. A functional understanding of the mechanism through which hyperaccumulator plants accumulate and tolerate extremely toxic metals is a prerequisite for the development of novel strategies for improving phytoremediation using engineered plants or natural hyperaccumulators as well as biofortification and food crop safety. Most hyperaccumulator species, however, are small and slow-growing, and their potential for large-scale decontamination of polluted soils is limited. Sedum alfredii Hance, the only one metal hyperaccumulator from the Crassulaceae family, is an ideal candidate for gaining a functional understanding of the intra family hyperaccumulation mechanisms as well as their potential applications. In the present study, we isolated and functionally characterized a P1B-type ATPase gene (SaHMA3) from S. alfredii Hance. SaHMA3 alleles from a hyperaccumulating ecotype (HE) and non-hyperaccumulating ecotype (NHE) were constitutively expressed in both shoot and root and encoded tonoplast-localized proteins, but showed differences in transport substrate specificity and expression level. SaHMA3 h from the HE plant was a Cd transporter. In contrast, SaHMA3n from NHE plants was able to transport both Zn and Cd. SaHMA3 showed a significantly higher constitutive expression level in HE plants than in NHE plants. Furthermore, the expression level of SaHMA3 in the shoots of HE plants was considerably higher than in the roots. Overexpression of SaHMA3h in tobacco plants significantly enhanced Cd tolerance and accumulation and greatly increased the root sequestration of Cd. In summary, our data suggested that SaHMA3 plays critical roles in Cd hyperaccumulation and hypertolerance in Cd hyperaccumulator S. alfredii Hance. PMID- 26547195 TI - Concentration-Dependent Mechanism Alteration of Pleurocidin Peptide in Escherichia coli. AB - Cationic antimicrobial peptides (CAPs) are essential components of the innate immune system. Most CAPs exert antimicrobial effects via membrane-active mechanisms, while high concentrations of CAPs are associated with non-selective cytotoxicity. We originally hypothesized that a sub-lethal concentration of CAPs was able to exert antibacterial activity, by interacting with negatively charged nucleic acids, and not by damaging bacterial membranes. We selected pleurocidin (Ple) and Escherichia coli as experimental models of CAPs and bacteria, respectively. Whereas Ple distinctly acted on bacterial membranes in a concentration-dependent manner, the cell viability was almost similar regardless the peptide concentration. To address how Ple retained its antibacterial activity in a low concentration, we particularly focused on the induction of intracellular apoptosis-like death (ALD). Finally, it was suggested that a sub-lethal concentration of Ple led to ALD in E. coli, mediated by caspase-like protein and RecA. To the best of our knowledge, this is the first study showing that alterations of CAP mechanisms are concentration dependent in bacteria. PMID- 26547196 TI - Perinatal Treatments with the Dopamine D2-Receptor Agonist Quinpirole Produces Permanent D2-Receptor Supersensitization: a Model of Schizophrenia. AB - Repeated daily treatments of perinatal rats with the dopamine D2-receptor (D2-R) agonist quinpirole for a week or more produces the phenomenon of 'priming' gradual but long-term sensitization of D2-R. In fact a daily dose of quinpirole as low as 50 ug/kg/day is adequate for sensitizing D2-R. Primed rats as neonates and in adolescence, when acutely treated with quinpirole display enhanced eating/gnawing/nursing on dams, also horizontal locomotor activity. Between 3 and 5 weeks of age, acute quinpirole treatment of primed rats produces profound vertical jumping with paw treading-a behavior that is not observed in control rats. At later ages acute quinpirole treatment is associated with enhanced yawning, a D2-R-associated behavior. This long-term D2-R supersensitivity is believed to be life-long, despite the relatively brief period of D2-R priming near the time of birth. D2-R supersensitivity is not associated with an increase in the number or affinity of D2-R, as assessed in the striatum of rats; nor is it induced with the D3-R agonist 7-OH-DPAT. However, quinpirole-induced D2-R supersensitivity is associated with cognitive deficits, also a deficit in pre pulse inhibition and in neurotrophic factors, and low levels of the transcript regulator of G-protein signaling (RGS) RGS9 in brain; and acute reversal of these alterations by the antipsychotic agent olanzapine. In sum, rats ontogenetically D2-R supersensitized have face validity, construct validity and predictive ability for schizophrenia. PMID- 26547198 TI - Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior. AB - Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 uM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction. PMID- 26547199 TI - Cost Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccination Program in Chronic Obstructive Pulmonary Disease Patients Aged 50+ Years in Spain. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of pneumococcal infection. A 13-valent pneumococcal conjugate vaccine (PCV13) was approved for protection against invasive disease and pneumonia caused by Streptococcus pneumoniae in adults. This study estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD patients >=50 years old with PCV13 compared with current vaccination policy (CVP) with 23 valent pneumococcal polysaccharide vaccine. METHODS: A Markov model accounting for the risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD) was developed. All parameters, such as disease incidence and costs (?; 2015 values), were based on published data. The perspective of the analysis was that of the Spanish National Healthcare System, and the horizon of evaluation was lifetime in the base case. Vaccine effectiveness considered waning effect over time. Outcomes and costs were both discounted by 3% annually. RESULTS: Over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2224 cases of inpatient NBP, 3134 cases of outpatient NBP, and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. The ICER was ?1518 per quality adjusted life-year (QALY) gained for PCV13 versus CVP. PCV13 was found to be cost effective versus CVP from a 5-year modelling horizon (1302 inpatient NBP and 1835 outpatient NBP cases together with 182 deaths would be prevented [ICER ?25,573/QALY]). Univariate and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: At the commonly accepted willingness-to-pay threshold of ?30,000/QALY gained, PCV13 vaccination in COPD patients aged >=50 years was a cost-effective strategy compared with CVP from 5 years to lifetime horizon in Spain. PMID- 26547200 TI - The Impact of Ramucirumab on Survival in Patients with Advanced Solid Tumors: A Systematic Review and Meta-Analysis of Randomized II/III Controlled Trials. AB - BACKGROUND AND OBJECTIVES: Ramucirumab is a fully immunoglobulin G (lgG) monoclonal antibody targeting vascular endothelial growth factor receptor type 2 (VEGFR2). Previous clinical trials suggested ramucirumab could improve the survival and increase the risk of adverse effects. Here, we aimed to assess the efficacy and safety of ramucirumab in the treatment of advanced solid tumors. METHODS: Publications were searched from Pubmed, Embase database and clinicaltrials.gov. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated to evaluate efficacy, and the risk ratio (RR) for adverse effects. RESULTS: Ten relevant studies were included. Ramucirumab resulted in significant benefit in overall survival [OS, HR and 95% CI 0.87 (0.82-0.93), I(2): 0.0%] and progression-free survival [PFS, HR and 95% CI 0.74 (0.66-0.82), I(2): 67.4%]. Also the difference of time to progression (TTP) and objective response rate (ORR) between two groups were also significant [0.70 (0.57-0.88) and 1.78 (1.40 2.25), respectively]. Ramucirumab could increase the risk of total adverse effects (TAEs, of any grade) by 1% (from 0 to 2%) and severe adverse effects (SAEs, grade > 2) by 17% (from 9 to 26%). The most frequently occurring TAEs were fatigue (54.71%), neutropenia (42.74%), bleeding (37.55%), nausea (34.63%) and stomatitis (33.74%). Most frequently occurring SAEs (grade >=3) were neutropenia (33.43%), fatigue (12.08%), leukopenia (10.59%), hypertension (8.99%) and liver injury (8.74%). CONCLUSION: Ramucirumab could improve OS and PFS for patients suffering from advanced solid tumors. Ramucirumab could increase the risk of TAEs and SAEs. PMID- 26547201 TI - Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. AB - PURPOSE: Characterization of the human microbiome has become more precise with the application of powerful molecular tools utilizing the unique 16S ribosomal subunit's hypervariable regions to greatly increase sensitivity. The microbiome of the lower genital tract can prognosticate obstetrical outcome while the upper reproductive tract remains poorly characterized. Here, the endometrial microbiome at the time of single embryo transfer (SET) is characterized by reproductive outcome. METHODS: Consecutive patients undergoing euploid, SET was included in the analysis. After embryo transfer, performed as per routine, the most distal 5 mm portion of the transfer catheter was sterilely placed in a DNA free PCR tube. Next-generation sequencing of the bacteria specific 16S ribosome gene was performed, allowing genus and species calls for microorganisms. RESULTS: Taxonomy assignments were made on 35 samples from 33 patients and 2 Escherichia coli controls. Of the 33 patients, 18 had ongoing pregnancies and 15 did not. There were a total of 278 different genus calls present across patient samples. The microbiome at time of transfer for those patients with ongoing pregnancy vs. those without ongoing pregnancy was characterized by top genera by sum fraction. Lactobacillus was the top species call for both outcomes. CONCLUSIONS: The data presented here show the microbiome at the time of embryo transfer can successfully be characterized without altering standard clinical practice. This novel approach, both in specimen collection and analysis, is the first step toward the goal of determining physiologic from pathophysiologic microbiota. Further studies will help delineate if differences in the microbiome at the time of embryo transfer have a reliable impact on pregnancy outcome. PMID- 26547197 TI - The Role of Proteases in Hippocampal Synaptic Plasticity: Putting Together Small Pieces of a Complex Puzzle. AB - Long-term synaptic plasticity in the hippocampus is thought to underlie the formation of certain forms of memory, including spatial memory. The early phase of long-term synaptic potentiation and synaptic depression depends on post translational modifications of synaptic proteins, while protein synthesis is also required for the late-phase of both forms of synaptic plasticity (L-LTP and L LTD). Numerous pieces of evidence show a role for different types of proteases in synaptic plasticity, further increasing the diversity of mechanisms involved in the regulation of the intracellular and extracellular protein content. The cleavage of extracellular proteins is coupled to changes in postsynaptic intracellular mechanisms, and additional alterations in this compartment result from the protease-mediated targeting of intracellular proteins. Both mechanisms contribute to initiate signaling cascades that drive downstream pathways coupled to synaptic plasticity. In this review we summarize the evidence pointing to a role for extracellular and intracellular proteases, with distinct specificities, in synaptic plasticity. Where in the cells the proteases are located, and how they are regulated is also discussed. The combined actions of proteases and translation mechanisms contribute to a tight control of the synaptic proteome relevant for long-term synaptic potentiation and synaptic depression in the hippocampus. Additional studies are required to elucidate the mechanisms whereby these changes in the synaptic proteome are related with plasticity phenomena. PMID- 26547203 TI - Tales of methylomes and centrosomes in the human embryo. PMID- 26547202 TI - Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization. AB - PURPOSE: Higher risk for birth of singletons being large for gestational age (LGA) has been revealed after in vitro fertilization (IVF) frozen-thawed embryo transfer (FET). This phenomenon is now being investigated, since there is a speculation that these neonates could suffer from underlying epigenetic disturbances. The aim of the study was to expose independent LGA risk factors and to identify those connected to the IVF techniques. METHODS: Altogether, 4508 singleton pregnancies and births were included in the cohort case-matched study. Two hundred eleven singleton pregnancies and births after FET and 916 after fresh embryo transfer (ET) were included into two study groups. The IVF procedures were performed at the University Medical Centre Ljubljana between 2004 and 2011. For each IVF pregnancy, three matched consecutive controls after natural conception were included. Using logistic regression models, we observed LGA connection to maternal parameters (smoking, hypertension, parity, BMI, gestational diabetes, IVF conception, FET, double ET, and ICSI procedure). RESULTS: Singletons born after FET had a significantly higher risk for being LGA (p = 0.032; OR 1.697; 95 % CI 1.047-2.752). BMI 25-30 was a significant independent risk factor for LGA in the IVF groups (FET p = 0.041, OR 2.460, 95 % CI 1.030-5.857 and fresh ET p = 0.003; OR 2.188, 95 % CI 1.297-3.691). ICSI and double ET had no significant effect on LGA occurrence. CONCLUSIONS: Besides maternal BMI, FET is a significant independent LGA risk factor in IVF patients. Other observed factors (smoking, hypertension, multiparity, GDM, ICSI procedure, or number of embryos transferred) do not influence LGA risk significantly. PMID- 26547204 TI - Confirmation rates of array-CGH in day-3 embryo and blastocyst biopsies for preimplantation genetic screening. AB - PURPOSE: The purpose of this study was to compare the confirmation rate of day-3 embryo biopsy (blastomere) and trophectoderm biopsy using array-comparative genomic hybridization (array-CGH) technology. METHODS: A blinded study was conducted to re-analyse 109 embryos previously diagnosed as chromosomally abnormal by array-CGH. Preimplantation genetic screening (PGS) was performed using array-CGH on day 3 (n = 50) or day 5 (n = 59). Partial chromosome gains or losses were excluded (n=6), and only whole chromosome aneuploidies were considered. Re-analysis of whole blastocysts was carried out following the same array-CGH protocol used for PGS. RESULTS: The PGS result was confirmed in the whole blastocyst in (a) 49/50 (98 %) abnormal embryos after day-3 biopsy and (b) 57/59 (96.6 %) abnormal embryos after trophectoderm biopsy. One embryo (1/50; 2 %) was diagnosed as abnormal, with monosomy 18, on day 3, and software analysis of the whole blastocyst gave a euploid result; however, a mosaic pattern was observed for monosomy 18 in the whole blastocyst. Two trophectoderm biopsy cases (3.4 %) did not have the abnormalities (trisomy 7, and trisomy 1 and 4, respectively) verified in the whole embryo. Concordance rates for both biopsy strategies and for individual chromosomes were evaluated by Fisher's exact test and showed no significant differences. CONCLUSIONS: Both types of biopsies showed similar high concordance rates with whole blastocyst results. Therefore, regarding the confirmation rates shown in this work, day-3 embryo biopsies can be representative of the whole embryo and both types of biopsy can be used for clinical analysis in PGS following the described array-CGH protocol. PMID- 26547205 TI - Clinical significance of FABP2 expression in newborns with necrotizing enterocolitis. AB - BACKGROUND: This meta-analysis aimed to determine the role of human fatty acid binding protein 2 (FABP2) expression in the diagnosis of necrotizing enterocolitis (NEC) of newborns. DATA SOURCES: Eligible studies for further statistical analysis were identified from various databases including PubMed, Expert Medica Database, Web of Science, Cochrane Library, Google Scholar, China BioMedicine and China National Knowledge Infrastructure. Random effects model was used, and summary standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated to assess the association of FABP2 expression and NEC. RESULTS: Ten articles which included 572 infants (262 infants with NEC and 310 healthy controls) were included in the current meta-analysis. FABP2 showed a positive relationship with NEC of newborns (SMD=2.88, 95% CI=2.09-3.67, P<0.001). And FABP2 expression was higher in patients with advanced stage of NEC (stage III or stage II+III) than in those with early stage of NEC (stage I) (SMD=-0.48, 95% CI=-0.87 to -0.09, P=0.015). Ethnicity-stratified analysis yielded significantly different estimates with a high FABP2 expression in NEC in both Caucasians (SMD=3.16, 95% CI=1.90-4.43, P<0.001) and Asians (SMD=2.57, 95% CI=1.50-3.64, P<0.001). Sample-based subgroup analysis showed that FABP2 expression was positively correlated with neonatal NEC in both urinary- and blood-sample subgroups (all P<0.05). CONCLUSION: The results prove that the high FABP2 expression is related to the damage to intestinal cells, which may be a possible early detection marker identifying neonatal NEC. PMID- 26547206 TI - Heat shock protein 70-2 and tumor necrosis factor-alpha gene polymorphisms in Chinese children with Henoch-Schonlein purpura. AB - BACKGROUND: Henoch-Schonlein purpura (HSP) or IgA-associated vasculitis is related to immune disturbances. Polymorphisms of the heat shock protein 70-2 gene (HSP70-2) and the tumor necrosis factor-a gene (TNF-alpha) are known to be associated with immune diseases. The purpose of this study was to investigate the likely association of HSP70-2 (+1267A/G) and TNF-alpha (+308A/G) gene polymorphisms with HSP in children. METHODS: The polymerase chain reaction restriction fragment length polymorphism method was used to detect the HSP70-2 and TNF-alpha polymorphisms in 205 cases of children with HSP and 53 controls; and the association of these polymorphisms with HSP and HSP nephritis (HSPN) was analyzed. RESULTS: The G/G genotypic frequencies at the +1267A/G position of HSP70-2 in the HSP group (22.9%) were significantly higher than those in the healthy control group (9.4%) (chi(2)=4.764, P<0.05). The frequencies of the A/A, A/G and G/G genotypes of HSP70-2 in patients in the nephritis-free group and the HSPN group showed no statistically significant difference. The A/A genotype frequency at the +308G/A position of TNF-alpha in the HSP group was 8.3%, which was higher than that in the control group (chi(2)=6.447, P<0.05). The A allele frequency of TNF-alpha in the HSP group was higher than that in the control group, with a statistically significant difference (chi(2)=7.241, P<0.05). CONCLUSIONS: The HSP70-2 (+1267A/G) and TNF-alpha (+308G/A) gene polymorphisms were associated with HSP in children. The G/G homozygosity of HSP70-2 and the A/A homozygosity of TNF-alpha may be genetic predisposing factors for HSP. PMID- 26547207 TI - Population-based frequency of surfactant dysfunction mutations in a native Chinese cohort. AB - BACKGROUND: Rare mutations in surfactant-associated genes contribute to neonatal respiratory distress syndrome. The frequency of mutations in these genes in the Chinese population is unknown. METHODS: We obtained blood spots from the Guangxi Neonatal Screening Center in Nanning, China that included Han (n=443) and Zhuang (n=313) ethnic groups. We resequenced all exons of the surfactant proteins-B (SFTPB), -C (SFTPC), and the ATP-binding cassette member A3 (ABCA3) genes and compared the frequencies of 5 common and all rare variants. RESULTS: We found minor differences in the frequencies of the common variants in the Han and Zhuang cohorts. We did not find any rare mutations in SFTPB or SFTPC, but we found three ABCA3 mutations in the Han [minor allele frequency (MAF)=0.003] and 7 in the Zhuang (MAF=0.011) cohorts (P=0.10). The ABCA3 mutations were unique to each cohort; five were novel. The collapsed carrier rate of rare ABCA3 mutations in the Han and Zhuang populations combined was 1.3%, which is significantly lower than that in the United States (P<0.001). CONCLUSION: The population-based frequency of mutations in ABCA3 in south China newborns is significantly lower than that in United States. The contribution of these rare ABCA3 mutations to disease burden in the south China population is still unknown. PMID- 26547208 TI - Early term infants are at increased risk of requiring neonatal intensive care. AB - BACKGROUND: Increasing evidence is demonstrating that infants born early on during the term period are at increased risk of morbidity compared with infants born closer to a complete 40 week gestational pregnancy. The purpose of this study was to compare early term [gestation age (GA): 37-37 6/7 weeks] neonatal outcomes with those of other full term neonatal intensive care unit (NICU) admissions. METHODS: Retrospective chart review of all term infants admitted to the NICU at New York University Langone Medical Center over a 17 month period. Subjects were grouped and analyzed according to their GA at birth: 1) early term infants (GA between 37 0/7 to 37 6/7 weeks) and 2) other term infants (38 0/7 weeks and older). RESULTS: Early term infants were more likely to require NICU care than other term infants [relative risk: 1.42, 95% confidence interval (CI)=1.07-1.88), P=0.01]. In the NICU, they are more likely to manifest respiratory distress syndrome [odds ratio (OR)=5.7, 95% CI=1.6-19.8, P<0.01] and hypoglycemia (OR=4.6, 95% CI=2.0-10.4, P<0.001). In addition, early term neonates were more likely to be born via elective cesarean section than other term neonates (OR=4.1, 95% CI=2.0-8.5, P<0.001). CONCLUSIONS: Being born at early term is associated with increased risk of respiratory disease and hypoglycemia requiring neonatal intensive care. Further efforts directed at decreasing early term deliveries may be warranted. PMID- 26547209 TI - Not just a capillary hemangioma. PMID- 26547210 TI - Stop tarnishing steroid and Chinese medicine. PMID- 26547212 TI - Interlabial mass in a neonate with paraurethral cyst. PMID- 26547211 TI - Molecular medicine of fragile X syndrome: based on known molecular mechanisms. AB - BACKGROUND: Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. DATA SOURCES: Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. RESULTS: The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. CONCLUSIONS: Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments. PMID- 26547213 TI - Tonsillitis in children: unnecessary laboratory studies and antibiotic use. AB - BACKGROUND: The Finnish Current Care Guidelines on diagnostics and treatment of sore throat recommend the treatment of only group A streptococcus (GAS) positive cases with penicillin. The aim of the study was to evaluate how these guidelines are followed in the pediatric emergency unit. METHODS: We analyzed retrospectively the data on microbiological studies and blood tests done, and data on prescribing of antibiotics, of 200 children admitted for febrile exudative tonsillitis. RESULTS: After the clinical diagnosis of exudative tonsillitis, antigen test and/or culture for GAS identification was done in >95% of cases. All the 32 (16%) children with GAS infection, but also 52 (38%) of the 137 children without any evidence of bacterial infection received antibiotics. Additional laboratory studies were done in 96% of children. Serum C-reactive concentrations or white blood cell counts were not able to separate streptococcal from non-streptococcal tonsillitis. No serious bacterial infection was diagnosed. CONCLUSIONS: The Finnish Current Care Guidelines lead to over-treatment with antibiotics. None of the 200 children returned after discharge, suggesting that undertreatment did not happen. PMID- 26547214 TI - Systemic Agents for Severe Atopic Dermatitis in Children. AB - Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic, scaly, erythematous papules and plaques frequently associated with superinfection. The lifelong prevalence of AD is over 20 % in affluent countries. When a child with severe AD is not responding to optimized topical therapy including phototherapy, and relevant triggers cannot be identified or avoided, systemic therapy should be considered. If studies show early aggressive intervention can prevent one from advancing along the atopic march, and relevant triggers such as food allergies cannot be either identified or avoided, systemic therapy may also play a prophylactic role. Though the majority of evidence exists in adult populations, four systemic non-specific immunosuppressive or immunomodulatory drugs have demonstrated efficacy in AD and are used in most patients requiring this level of intervention regardless of age: cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. This article reviews the use of these medications as well as several promising targeted therapies currently in development including dupilumab and apremilast. We briefly cover several other systemic interventions that have been studied in children with atopic dermatitis. PMID- 26547215 TI - Anacardic acid and thyroid hormone enhance cardiomyocytes production from undifferentiated mouse ES cells along functionally distinct pathways. AB - The epigenetics of early commitment to embryonal cardiomyocyte is poorly understood. In this work, we compared the effect of thyroid hormone and that of anacardic acid, a naturally occurring histone acetylase inhibitor, or both in combination, on mouse embryonic stem cells (mES) differentiating into embryonal cardiomyocyte by embryoid bodies (EBs) formation. Although the results indicated that anacardic acid (AA) and thyroid hormone were both efficient in promoting cardiomyocyte differentiation, we noticed that a transient exposure of mES to AA alone was sufficient to enlarge the beating areas of EBs compared to those of untreated controls. This effect was associated with changes in the chromatin structure at the promoters of specific cardiomyogenic genes. Among them, a rapid induction of the transcription factor Castor 1 (CASZ1), important for cardiomyocytes differentiation and maturation during embryonic development, was observed in the presence of AA. In contrast, thyroid hormone (T 3) was more effective in stimulating spontaneous firing, thus suggesting a role in the production of a population of cardiomyocyte with pacemaker properties. In conclusion, AA and thyroid hormone both enhanced cardiomyocyte formation along in apparently distinct pathways. PMID- 26547216 TI - Usefulness of NRAS codon 61 mutation analysis and core needle biopsy for the diagnosis of thyroid nodules previously diagnosed as atypia of undetermined significance. AB - A repeat fine needle aspiration (FNA) is recommended for thyroid nodules diagnosed as atypia of undetermined significance (AUS) in a previous cytology. We evaluated the utility of NRAS codon 61 (NRAS61) mutation analysis and core needle biopsy (CNB) for the diagnosis of thyroid nodules previously diagnosed as AUS. This study enrolled 236 patients who underwent both NRAS61 mutation analysis and CNB of thyroid nodules previously diagnosed as AUS at cytology. The NRAS61 mutation was detected in 36 nodules and was more frequently detected in the AUS and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN) categories, as determined by histological analysis of CNB, than in the benign group (p = 0.005). Sixty-one patients underwent surgery, and 29 nodules were finally diagnosed as malignant after surgery. Among 61 patients who underwent surgery, nodules with the NRAS61 mutation (42-65 %) had a significantly higher malignancy rate than nodules with wild-type NRAS61 (7-37 %, p = 0.038). The association between malignancy and the NRAS61 mutation was significant after adjusting for age, sex, nodule size, and histological diagnosis of CNB (p = 0.01). NRAS61 mutation analysis together with CNB could be helpful for arriving at a clinical decision in patients with thyroid nodules showing AUS in a previous cytology. PMID- 26547217 TI - Vitamin D-binding protein and free vitamin D concentrations in acromegaly. AB - Free 25-hydroxyvitamin D [25(OH)D] is suggested to be important in the determination of vitamin D deficiency, since vitamin D-binding protein (VDBP) may affect total 25(OH)D levels. There are no data about free 25(OH)D concentrations in acromegaly. We aimed to investigate serum VDBP and total and free 25(OH)D levels in patients with acromegaly in comparison with control subjects. We recruited 54 patients with acromegaly and 32 control subjects who were similar according to age, gender, and body mass index. Serum VDBP levels were found to be increased in patients with acromegaly compared to control subjects [90.35 (72.45 111.10) vs. 69.52 (63.89-80.13) mg/l, p = 0.001]. There was statistically no significant difference in serum total 25(OH)D levels between the patients with acromegaly and control subjects [18.63 (13.35-27.73) vs. 22.51 (19.20-28.96) ng/ml, p = 0.05]. Free 25(OH)D levels were significantly decreased in patients with acromegaly compared to control subjects [14.55 (10.45-21.45) vs. 17.75 (15.30-23.75) pg/ml, p = 0.03]. Free 25(OH)D levels correlated positively with total 25(OH)D (p = 0.0001) and HDL cholesterol (p = 0.04) and negatively with fasting blood glucose (p = 0.04). Our findings indicate that VDBP is increased and free 25(OH)D is decreased in acromegaly, while there is no significant alteration in total 25(OH)D. PMID- 26547218 TI - Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. AB - In this study, we aimed to examine dynamic thiol/disulfide homeostasis in type 1 diabetes mellitus (T1DM) and identify the factors associated with thiol oxidation. Thirty-eight subjects (18 male, 20 female) diagnosed with T1DM and 38 (17 male, 21 female) healthy volunteers without any known diseases were included in the study. Thiol/disulfide homeostasis concentrations were measured by a newly developed method (Erel & Neselioglu) in this study. After native thiol, total thiol and disulfide levels were determined; measures such as disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were calculated. In T1DM patients, compared to the control group, disulfide (p = 0.024), disulfide/native thiol (p < 0.001), and disulfide/total thiol (p < 0.001) were determined higher, while native thiol (p = 0.004) and total thiol (p < 0.001) levels were much lower. In the patient group, a positive correlation was determined between c-reactive protein (r = 325, p = 0.007; r = 316, p = 0.010, respectively), fasting blood glucose (r = 279, p = 0.018; r = 251, p = 0.035, respectively), and glycosylated hemoglobin (r = 341, p = 0.004; r = 332, p = 0.005, respectively) and rates of disulfide/native thiol and disulfide/total thiol. We determined that thiol oxidation increase in T1DM patients compared to the control group. We thought that hyperglycemia and chronic inflammation might be the major cause of increase in oxide thiol form. In order to determine the relationship between the status of autoimmunity and dynamic thiol/disulfide in T1DM, dynamic thiol/disulfide homeostasis in newly diagnosed-antibody positive T1DM patients is required to be investigated. PMID- 26547219 TI - Deoxyribonuclease I gene polymorphism and susceptibility to systemic lupus erythematosus. AB - The DNASE1 gene is regarded as one of the susceptible genes for systemic lupus erythematosus (SLE). Recent studies have detected the presence of a variable number of tandem repeat (VNTR) polymorphisms at intron 4 in this gene. The current study aimed to investigate the influence of current polymorphism on SLE susceptibility in a sample of the Iranian population. The study included 163 patients and 180 unrelated healthy controls. The VNTR polymorphisms in the DNASE1 gene were determined by polymerase chain reaction (PCR). The genotypic frequency investigation indicated that 3/6 genotype frequency in patients affected with SLE was more than healthy controls (P = 0.004). Moreover, 3/4 and 4/6 genotype frequencies in healthy cohort were further in comparison with patient cohort (P = 0.0001). Findings of the present study manifested that 3/6 genotype in patients affected with SLE was significantly more than healthy controls, thus it can be regarded as a risk factor, while 3/4 and 4/6 genotypes were significantly higher in healthy controls which can be considered as a protective factor. PMID- 26547220 TI - IL-37 inhibits the production of pro-inflammatory cytokines in MSU crystal induced inflammatory response. AB - Acute gouty arthritis (AGA) is an auto-inflammatory disease characterized by resolving spontaneously, which suggests that negative feedback loops control inflammatory and immunological responses to monosodium urate (MSU) crystals. By now, the molecular mechanism for spontaneous resolution of acute GA remains unclear; this study was undertaken to evaluate whether IL-37 is involved in spontaneous resolution of AGA. A total of 45 acute GA (AGA),29 non-acute GA (NAGA) male patients and 82 male health control (HC) were involved in this study, we measured IL-7 expression in the peripheral blood mononuclear cells (PBMCs), together with levels of IL-1beta, IL-6, IL-10, TNF-alpha and TGF-beta1 in the serum. Further, we either inhibited IL-37 expression in human PBMCs with siRNA or over-expressed the cytokine in human macrophages. Pro-inflammatory cytokine IL 1beta, IL-6, and TNF-alpha expressions were significantly higher in the AGA group than in the NAGA or HC group (P < 0.05, respectively). However, anti-inflammatory IL-37, TGF-beta1, and IL-10 were greater in the NAGA group than in the AGA and HC groups (P < 0.05, respectively). Expression of IL-37 in MSU crystal-treated macrophages inhibited the expression of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. However, anti-inflammatory TGF-beta1 and IL-10 expressions in these supernatants were unaffected by over-expression or knockdown of IL-37. Our study indicates that IL-37 is an important anti-inflammatory cytokine in AGA by suppressing the production of pro-inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GA. PMID- 26547221 TI - Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease. AB - Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjogren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 +/- 18.00 ng/ml), compared to patients with RA (39.17 +/- 18.90 ng/ml), pSS (35.31 +/- 19.47 ng/ml), SLE (32.21 +/- 25.01 ng/ml), OA (19.24 +/- 10.67 ng/ml), and HCs (8.46 +/- 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1%, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin positive patients compared to negative patients in AOSD (103.49 +/- 20.21 g/l vs 115.71 +/- 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent. PMID- 26547222 TI - Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity. AB - Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas kidney (SPK) transplants for over 25 years and find that 6-8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches. PMID- 26547224 TI - Challenges in the adjudication of major bleeding events in acute coronary syndrome: a plea for a standardized approach and guidance to adjudication. PMID- 26547225 TI - How to treat Marfan syndrome: an update. PMID- 26547223 TI - Exercise Improves Clinical Symptoms, Quality of Life, Global Functioning, and Depression in Schizophrenia: A Systematic Review and Meta-analysis. AB - BACKGROUND: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. METHODS: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges' g. RESULTS: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges' g = .39, P < .001), positive (k = 15, n = 715: Hedges' g = .32, P < .01), negative (k = 18, n = 854: Hedges' g = .49, P < .001), and general (k = 10, n = 475: Hedges' g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges' g = .55, P < .001), global functioning (k = 5, n = 342: Hedges' g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges' g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges' g = .32, P < .05), while exercise in general or in any other form had no effect on cognition. CONCLUSION: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga. PMID- 26547226 TI - A Randomized Trial of Cardiovascular Responses to Energy Drink Consumption in Healthy Adults. PMID- 26547227 TI - [Literature review of the importance of retinal examination in two genetic neuromuscular diseases (DM1 and FSHD). Potential clinical applications]. PMID- 26547228 TI - [Unilateral posterior form of persistent hyperplastic primary vitreous]. PMID- 26547229 TI - [Visual acuity, pachymetry and corneal density after 5% sodium chloride treatment in corneal edema after surgery]. AB - PURPOSE: To evaluate the effectiveness of a hyperosmolar medication in corneal edema. METHODS: This was a prospective randomized study, performed in patients with post-operative corneal edema. Two groups were created: group 1 treated with hypertonic eye drops of 5% sodium chloride with 0.15% sodium hyaluronate in addition to the usual post-operative treatment for 1 month; group 2 without treatment for edema. Visual acuity, pachymetry and corneal density were measured at 1 day, 1 week, 1 month, 3 months and 6 months following surgery. RESULTS: Forty-four patients were included in group 1 and 42 in group 2. Visual acuity was significantly better in group 1 than in group 2 at 7 days (0.84 logMAR vs 1.55 logMAR, P=0.019 CI 95% [-1.298;-0.128]) and was no longer different at one month, three and six months. Pachymetry decreased significantly in 7 days in group 1 (decrease of 17%, P=0.04, CI 95% [1.987; 258.305]), compared to group 2 (P=0.8, CI 95% [-132.9; 161.8]), but the difference between the 2 groups was not statistically significant (P=0.11, CI 95% [-16; 19.1]). Corneal density was also not significantly different between the two groups. CONCLUSION: Five percent sodium chloride hypertonic eye drops show a statistically significant reduction in post-operative corneal edema as shown by the improvement in visual acuity at one week and the downward trend in pachymetry. PMID- 26547230 TI - Comparison of transposon and deletion mutants in Mycobacterium tuberculosis: The case of rv1248c, encoding 2-hydroxy-3-oxoadipate synthase. AB - We compared phenotypes of five strains of Mycobacterium tuberculosis (Mtb) differing in their expression of rv1248c and its product, 2-hydroxy-3-oxoadipate synthase (HOAS), with a focus on carbon source-dependent growth rates and attenuation in mice. Surprisingly, an rv1248c transposon mutant on a CDC1551 background grew differently than an rv1248c deletion mutant on the same background. Moreover, the same rv1248c deletion in two different yet genetically similar strain backgrounds (CDC1551 and H37Rv) gave different phenotypes, though each could be complemented. Whole genome re-sequencing did not provide an obvious explanation for these discrepancies. These observations offer a cautionary lesson about the strength of inference from complementation and sequence analysis, and commend consideration of more complex phenomena than usually contemplated in Mtb, such as epigenetic control. PMID- 26547231 TI - [Multiple sites extrapodal actinomycetoma: Favorable outcome to treatment with a combination of cotrimoxazole and NSAI]. AB - Mycetoma is a bacteriological or fungal infectious disease affecting the skin and/or soft tissues, which can be complicated by bone involvement. The most common feature is a tumor of the foot, but extrapodal localizations have been described. We report one case of a 47-year-old man who presented with tumefaction of a leg with multiple skin fistulae. Histopathological examination permitted to confirm the diagnosis of actinomycetoma and TDM showed the degree of bone and soft tissues involvement. Our case was characterized by the very inflammatory aspect of the tumor, its localization to the leg without foot involvement, the modest functional signs compared to the importance of radiological bone involvements, the deep destruction of the fibula while the tibia was apparently intact and the good response to treatment. In spite of its characteristic features, diagnosis of mycetoma is still late in our country, often with bone and/or articular spread. Priority may be given to measures for reduction of mycetoma diagnosis lateness. PMID- 26547232 TI - 2-Arylquinazolin-4(3H)-ones: A novel class of thymidine phosphorylase inhibitors. AB - Thymidine phosphorylase (TP) over expression plays an important role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. In this regard, a series of twenty five 2-arylquinazolin-4(3H)-one derivatives 1-25 were evaluated for thymidine phosphorylase inhibitory activity. Six compounds 5, 6, 20, 2, 23, and 3 were found to be active against thymidine phosphorylase enzyme with IC50 values in the range of 42.9-294.6MUM. 7-Deazaxanthine (IC50=41.0+/-1.63MUM) was used as a standard inhibitor. Compound 5 showed a significant activity (IC50=42.9+/ 1.0MUM), comparable to the standard. The enzyme kinetic studies on the most active compounds 5, 6, and 20 were performed for the determination of their modes of inhibition, and dissociation constants Ki. All active compounds were found to be largely non-cytotoxic against the mouse fibroblast 3T3 cell line. This study identifies a novel class of thymidine phosphorylase inhibitors which may be further investigated as leads to develop therapeutic agents. PMID- 26547233 TI - Letter to the Editor regarding "Sinogenic intracranial abscesses". PMID- 26547234 TI - Comparing diffusion weighted MRI in the detection of post-operative middle ear cholesteatoma in children and adults. AB - INTRODUCTION: There is a limited evidence base for the use of diffusion weighted MRI (DWMRI) in the assessment of post-operative cholesteatoma in children. This is important to address as this technique is particularly relevant in a paediatric setting. METHODS: We searched a prospectively collected database of patients undergoing DWMRI for the assessment of residual and recurrent cholesteatoma. Imaging findings were correlated with findings at revision surgery. 320 investigations were divided into paediatric and adult groups (90 in children, 230 in adults) and compared. RESULTS: Operative findings were available for 158 cases, of which 54 were children. The accuracy of DWMRI in children was 96.3%, and in adults was 88.5%. There were no statistically significant differences in the sensitivity, specificity, positive or negative predictive values between adults and children. DISCUSSION: An increasing number of patients are not undergoing confirmatory surgery after negative DWMRI scans. False negative results are commonly secondary to small foci of disease; false positives have several possible causes. Performing MRI on children can be challenging, but sedation may be helpful in younger children. CONCLUSION: The performance of diffusion weighted MRI is similar in paediatric and adult settings. This study suggests that DWMRI may be used in clinical practice in a similar way in children and adults. PMID- 26547236 TI - The association between regular yoga and meditation practice and falls and injuries: Results of a national cross-sectional survey among Australian women. AB - INTRODUCTION: Falls are the leading cause of injuries in women across all ages. While yoga has been shown to increase balance, it has also been associated with injuries due to falls during practice. This study aimed to analyse whether regular yoga or meditation practice is associated with the frequency of falls and fall-related injuries in upper middle-aged Australian women. METHODS: Women aged 59-64 years from the Australian Longitudinal Study on Women's Health (ALSWH) were queried regarding falls and falls-related injuries; and whether they regularly practiced yoga or meditation. Associations of falls and falls-related injuries with yoga or meditation practice were analysed using chi-squared tests and multiple logistic regression modelling. RESULTS: Of 10,011 women, 4413 (44.1%) had slipped, tripped or stumbled, 2770 (27.7%) had fallen to the ground, 1398 (14.0%) had been injured as a result of falling, and 901 (9.0%) women had sought medical attention for a fall-related injury within the previous 12 months. Yoga or meditation was practiced regularly by 746 (7.5%) women. No associations of falls, fall-related injuries and treatment due to falls-related injury with yoga or meditation practice were found. DISCUSSION: No association between yoga or meditation practice and falls or fall-related injuries have been found. Further studies are warranted for conclusive judgement of benefits and safety of yoga and meditation in relation to balance, falls and fall-related injuries. PMID- 26547235 TI - Crowdsourced direct-to-consumer genomic analysis of a family quartet. AB - BACKGROUND: We describe the pioneering experience of a Spanish family pursuing the goal of understanding their own personal genetic data to the fullest possible extent using Direct to Consumer (DTC) tests. With full informed consent from the Corpas family, all genotype, exome and metagenome data from members of this family, are publicly available under a public domain Creative Commons 0 (CC0) license waiver. All scientists or companies analysing these data ("the Corpasome") were invited to return results to the family. METHODS: We released 5 genotypes, 4 exomes, 1 metagenome from the Corpas family via a blog and figshare under a public domain license, inviting scientists to join the crowdsourcing efforts to analyse the genomes in return for coauthorship or acknowldgement in derived papers. Resulting analysis data were compiled via social media and direct email. RESULTS: Here we present the results of our investigations, combining the crowdsourced contributions and our own efforts. Four companies offering annotations for genomic variants were applied to four family exomes: BIOBASE, Ingenuity, Diploid, and GeneTalk. Starting from a common VCF file and after selecting for significant results from company reports, we find no overlap among described annotations. We additionally report on a gut microbiome analysis of a member of the Corpas family. CONCLUSIONS: This study presents an analysis of a diverse set of tools and methods offered by four DTC companies. The striking discordance of the results mirrors previous findings with respect to DTC analysis of SNP chip data, and highlights the difficulties of using DTC data for preventive medical care. To our knowledge, the data and analysis results from our crowdsourced study represent the most comprehensive exome and analysis for a family quartet using solely DTC data generation to date. PMID- 26547237 TI - Sexual health and relationships after age 60. AB - A commonly used phrase describing aging is "60 is the new 40". Although in many aspects of life this may be correct, in discussing sexual health, challenges to maintaining excellent sexual health become more common around age 60. Biological aging challenges physical sexual activity and responsiveness. We commence by briefly surveying the extensive coverage of 'normal' physiological aging. We primarily focus on issues that arise in distinct disease and or pathophysiological states, including gynecological and breast cancer, as well as those associated with partners of men who are either prostate cancer survivors or who have taken therapy for erectile dysfunction (ED). Regrettably, there is a very modest literature on sexual health and associated possible interventions in older patients in these cohorts. We discuss a variety of interventions and approaches, including those that we have developed and applied in a clinic at our host university, which have generally produced successful outcomes. The extended focus to sexual relationship dynamics in partners of men with either prostate cancer or ED in particular is virtually unexplored, yet is especially timely given the large numbers of women who encounter this situation. Finally, we briefly discuss cross-cultural distinctions in older couples' expectations, which exhibit remarkable variation. PMID- 26547238 TI - Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation. AB - Cell differentiation usually occurs with high fidelity, but the expression of many transcription factors is variable. Using the touch receptor neurons (TRNs) in C. elegans, we found that the Hox proteins CEH-13/lab and EGL-5/Abd-B overcome this variability by facilitating the activation of the common TRN fate determinant mec-3 in the anterior and posterior TRNs, respectively. CEH-13 and EGL-5 increase the probability of mec-3 transcriptional activation by the POU homeodomain transcription factor UNC-86 using the same Hox/Pbx binding site. Mutation of ceh-13 and egl-5 resulted in an incomplete (~40%) loss of the TRN fate in respective TRNs, which correlates with quantitative mRNA measurements showing two distinct modes (all or none) of mec-3 transcription. Therefore, Hox proteins act as transcriptional "guarantors" in order to ensure reliable and robust gene expression during terminal neuronal differentiation. Guarantors do not activate gene expression by themselves but promote full activation of target genes regulated by other transcription factors. PMID- 26547239 TI - Small Molecules Take A Big Step Against Clostridium difficile. AB - Effective treatment of Clostridium difficile infections demands a shift away from antibiotics towards toxin-neutralizing agents. Work by Bender et al., using a drug that attenuates toxin action in vivo without affecting bacterial survival, demonstrates the exciting potential of small molecules as a new modality in the fight against C. difficile. PMID- 26547240 TI - Keeping postdiction simple. AB - Postdiction effects are phenomena in which a stimulus influences the appearance of events taking place before it. In metacontrast masking, for instance, a masking stimulus can render a target stimulus shown before the mask invisible. This and other postdiction effects have been considered incompatible with a simple explanation according to which (i) our perceptual experiences are delayed for only the time it takes for a distal stimulus to reach our sensory receptors and for our neural mechanisms to process it, and (ii) the order in which the processing of stimuli is completed corresponds with the apparent temporal order of stimuli. As a result, the theories that account for more than a single postdiction effect reject at least one of these theses. This paper presents a new framework for the timing of experiences-the non-linear latency difference view-in which the three most discussed postdiction effects-apparent motion, the flash-lag effect, and metacontrast masking-can be accounted for while simultaneously holding theses (i) and (ii). This view is grounded in the local reentrant processes, which are known to have a crucial role in perception. Accordingly, the non-linear latency difference view is both more parsimonious and more empirically plausible than the competing theories, all of which remain largely silent about the neural implementation of the mechanisms they postulate. PMID- 26547241 TI - Clinical assessment of endothelial function in patients with rheumatoid arthritis: A meta-analysis of literature studies. AB - BACKGROUND: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with rheumatoid arthritis (RA). Flow-mediated (FMD) and nitrate-mediated dilation (NMD) are considered non-invasive methods to assess endothelial function and surrogate markers of subclinical atherosclerosis. METHODS: We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of RA on FMD and NMD. Studies evaluating the relationship between RA and markers of CV risk (FMD and NMD) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. The random-effect method was used for analyses and results were expressed as mean difference (MD). RESULTS: A total of 20 studies (852 RA patients, 836 controls) were included in the final analysis. In detail, 20 studies with data on FMD (852 cases, 836 controls) and 5 studies with data on NMD (207 cases, 147 controls) were analyzed. Compared to controls, RA patients showed a significantly lower FMD (MD: -2.16%; 95% CI: -3.33, -0.98; P=0.0003), with no differences in NMD (MD: -0.41%; 95% CI: -2.89, 2.06; P=0.74). Interestingly, a lower FMD (MD: -2.00%; 95% CI: -3.20, -0.80; P=0.001) and no differences in NMD (P=0.49) were confirmed when excluding data on patients with early-RA. Meta regression models showed that a more severe inflammatory status was associated with a more significant impairment in FMD. CONCLUSIONS: RA patients show impaired FMD, which is currently considered an independent predictor of CV events. The presence of endothelial dysfunction in RA should be taken into account to plan adequate prevention strategies and therapeutic approaches. PMID- 26547242 TI - Finite-time synchronization of fractional-order memristor-based neural networks with time delays. AB - In this paper, we consider the problem of finite-time synchronization of a class of fractional-order memristor-based neural networks (FMNNs) with time delays and investigated it potentially. By using Laplace transform, the generalized Gronwall's inequality, Mittag-Leffler functions and linear feedback control technique, some new sufficient conditions are derived to ensure the finite-time synchronization of addressing FMNNs with fractional order alpha:16. PMID- 26547270 TI - Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment. AB - In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARgamma, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009 2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. PMID- 26547271 TI - Emerging programmed aging mechanisms and their medical implications. AB - For many generations programmed aging in humans was considered theoretically impossible and medical attempts to treat or delay age-related diseases were based on non-programmed aging theories. However, there is now an extensive theoretical basis for programmed mammal aging and substantially funded medical research efforts based on programmed aging theories are underway. This article describes the very different disease mechanism concepts that logically result from the theories and the impacts emerging programmed aging mechanisms will have on funding and performing medical research on age-related conditions. PMID- 26547272 TI - The tuberculosis spectrum: Translating basic research into pediatric clinical practice. AB - Recent studies suggest that the classical dichotomous classification of "active" and "latent" tuberculosis (TB) is no longer acceptable since "TB infection" encompasses a wide spectrum of conditions ranging from asymptomatic to lethal disease. In an attempt to address these issues from a pediatric clinical perspective, we describe two children with microbiologically confirmed TB but lacking any clinical and radiological evidence of disease. These two cases highlight the hypothesis that TB cannot be divided in two simple categories, but it covers a wide spectrum of manifestations ranging from asymptomatic to lethal TB. The implications of these results in the context of the new TB spectrum and the related clinical issues are discussed. PMID- 26547273 TI - Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia. AB - For more than a century type 2 diabetes has been looked upon mainly as an insulin related disease and it is well-acknowledged that insulin resistance and beta cell dysfunction play important roles in the pathophysiology of the disease. During the last couple of decades, glucagon has also been recognised to play a significant role in type 2 diabetic pathophysiology. However, the mechanisms underlying disturbances in the regulation of glucagon remain unclear. Glucagon constitutes the primary stimulus for hepatic glucose production and, thus, upholds adequate blood glucose levels during fasting conditions. Many - but not all - patients with type 2 diabetes are characterised by inappropriately elevated plasma levels of glucagon contributing to their hyperglycaemic state. We believe that phenotypical dissimilarities within this group of patients may determine the presence and degree of hyperglucagonaemia. Results from our group show that both normoglycaemic individuals and patients with type 2 diabetes with non-alcoholic fatty liver disease (NAFLD) exhibit fasting hyperglucagonaemia compared to similarly grouped individuals without NAFLD. Therefore, we speculate that NAFLD - and not type 2 diabetes per se - is the main driver behind fasting hyperglucagonaemia. We hypothesise that in the majority of type 2 diabetic individuals hepatic sensitivity to glucagon is compromised due to hepatic steatosis, and that this provides a feedback mechanism acting at the level of pancreatic alpha cells, leading to elevated levels of glucagon. Here we present our hypothesis and propose a way to test it. If our hypothesis holds true, hepatic glucagon resistance would constitute a parallel to the obesity-induced insulin resistance in muscle and liver tissue, and underpin a central role for glucagon in the pathogenesis of type 2 diabetes. This would provide a crucial step forward in understanding the interaction between NAFLD and the alpha cell in the pathophysiology underlying type 2 diabetes. PMID- 26547274 TI - Using a Systematic Approach and Theoretical Framework to Design a Curriculum for the Shaping Healthy Choices Program. AB - OBJECTIVE: To examine the use of a systematic approach and theoretical framework to develop an inquiry-based, garden-enhanced nutrition curriculum for the Shaping Healthy Choices Program. METHODS: Curriculum development occurred in 3 steps: identification of learning objectives, determination of evidence of learning, and activity development. Curriculum activities were further refined through pilot testing, which was conducted in 2 phases. Formative data collected during pilot testing resulted in improvements to activities. RESULTS: Using a systematic, iterative process resulted in a curriculum called Discovering Healthy Choices, which has a strong foundation in Social Cognitive Theory and constructivist learning theory. Furthermore, the Backward Design method provided the design team with a systematic approach to ensure activities addressed targeted learning objectives and overall Shaping Healthy Choices Program goals. CONCLUSIONS AND IMPLICATIONS: The process by which a nutrition curriculum is developed may have a direct effect on student outcomes. Processes by which nutrition curricula are designed and learning objectives are selected, and how theory and pedagogy are applied should be further investigated so that effective approaches to developing garden-enhanced nutrition interventions can be determined and replicated. PMID- 26547275 TI - Parental decision-making on utilisation of out-of-home respite in children's palliative care: findings of qualitative case study research - a proposed new model. AB - BACKGROUND: Respite in children's palliative care aims to provide a break for family's from the routine of caring. Parental decision-making regarding the utilisation of out-of-home respite is dependent on many interlinking factors including the child's age, diagnosis, geographical location and the family's capacity to meet their child's care needs. A proposed model for out-of-home respite has been developed based on the findings of qualitative case study research. METHODS: Utilising multiple, longitudinal, qualitative case study design, the respite needs and experiences of parents caring for a child with a life-limiting condition were explored. Multiple, in-depth interviews were undertaken with the parents identified by a hospital-based children's palliative care team. Data were analysed using thematic analysis. Each individual case consists of a whole study. Cross-case comparison was also conducted. RESULTS: Nine families were recruited and followed for two years. A total of 19 in-depth interviews were conducted with mothers and fathers (one or both) caring for a child with a life-limiting condition in Ireland. Each family reported vastly different needs and experiences of respite from their own unique perspective. Cross-case comparison showed that for all parents utilising respite care, regardless of their child's age and condition, home was the location of choice. Many interlinking factors influencing these decisions included: past experience of in-patient care, and trust and confidence in care providers. Issues were raised regarding the impact of care provision in the home on family life, siblings and the concept of home. CONCLUSION: Respite is an essential element of children's palliative care. Utilisation of out-of-home respite is heavily dependent on a number of interlinked and intertwined factors. The proposed model of care offers an opportunity to identify how these decisions are made and may ultimately assist in identifying the elements of responsive and family-focused respite that are important to families of children with life-limiting conditions. PMID- 26547276 TI - Individual and sex-related differences in pain and relief responsiveness are associated with differences in resting-state functional networks in healthy volunteers. AB - Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex-related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting-state network. In men, pain measures correlated with increased connectivity within the visual resting-state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions. PMID- 26547277 TI - Forebrain-independent generation of hyperthermic convulsions in infant rats. AB - Febrile seizures are the most common type of convulsive events in children. It is generally assumed that the generalization of these seizures is a result of brainstem invasion by the initial limbic seizure activity. Using precollicular transection in 13-day-old rats to isolate the forebrain from the brainstem, we demonstrate that the forebrain is not required for generation of tonic-clonic convulsions induced by hyperthermia or kainate. Compared with sham-operated littermate controls, latency to onset of convulsions in both models was significantly shorter in pups that had undergone precollicular transection, indicating suppression of the brainstem seizure network by the forebrain in the intact animal. We have shown previously that febrile seizures are precipitated by hyperthermia-induced respiratory alkalosis. Here, we show that triggering of hyperthermia-induced hyperventilation and consequent convulsions in transected animals are blocked by diazepam. The present data suggest that the role of endogenous brainstem activity in triggering tonic-clonic seizures should be re evaluated in standard experimental models of limbic seizures. Our work sheds new light on the mechanisms that generate febrile seizures in children and, therefore, on how they might be treated. PMID- 26547278 TI - Survey on multisensory feedback virtual reality dental training systems. AB - Compared with traditional dental training methods, virtual reality training systems integrated with multisensory feedback possess potentials advantages. However, there exist many technical challenges in developing a satisfactory simulator. In this manuscript, we systematically survey several current dental training systems to identify the gaps between the capabilities of these systems and the clinical training requirements. After briefly summarising the components, functions and unique features of each system, we discuss the technical challenges behind these systems including the software, hardware and user evaluation methods. Finally, the clinical requirements of an ideal dental training system are proposed. Future research/development areas are identified based on an analysis of the gaps between current systems and clinical training requirements. PMID- 26547279 TI - The histopathological and morphometric investigation of the effects of systemically administered humic acid on alveolar bone loss in ligature-induced periodontitis in rats. AB - BACKGROUND: Humic acid is a soil extract found widely around the world. This product includes some trace elements important for human's health. The purpose of this study was to evaluate the morphometric and histopathological changes associated with an experimental periodontitis model in rats in response to systemic administration of humic acid. MATERIAL AND METHODS: Thirty-eight male Wistar rats were divided into five experimental groups: non-ligated (NL, n = 6) group; ligature-only (LO, n = 8) group; ligature + systemic administration of humic acid (20, 80 and 150 mg/kg body weight per day for 15 d respectively) (S 20, S-80 and S-150) groups. 4/0 silk ligatures were placed at the gingival margin of lower first molars of the mandibular quadrant. The animals were killed at the end of 15 d. Changes in alveolar bone levels were clinically measured, using a stereomicroscope (* 25), as the distance from the cementoenamel junction to the alveolar bone crest. Tissues were histopathologically examined to assess the differences of osteoclast numbers, osteoblastic activity and inflammatory cell infiltration among the study groups. Enzyme-linked immunosorbent assay interleukin (IL)-1beta and IL-10 levels in serum and gingival homogenates were evaluated. RESULTS: At the end of 15 d, the alveolar bone loss was significantly higher in the LO group compared to the NL, S-80 and S-150 groups (p < 0.05). In addition, the alveolar bone loss in the S-80 group was significantly lower than the LO and S-20 groups (p < 0.05). The osteoblastic activity in the S-80 and S 150 groups was significantly higher than the other groups (p < 0.05). The osteoclast number in the LO group was significantly higher than the NL, S-80 and S-150 groups (p < 0.05). Inflammatory cell infiltration was significantly higher in LO and S-20 groups than the other groups (p < 0.05). The highest serum and gingival homogenate IL-10 levels were determined in the S-80 group (p < 0.05). The serum and gingival homogenate IL-1beta levels in the LO group were significantly higher than the other groups (p < 0.05). Both 80 and 150 mg/kg dosages of humic acid significantly reduced the periodontitis-related bone loss and inflammation, but the differences between these two groups were not statistically significant (p > 0.05). CONCLUSIONS: Within the limits of this study, it can be suggested that humic acid, when administered systemically as an 80 mg/kg dose, may prevent alveolar bone loss and reduce inflammation in the rat model. PMID- 26547280 TI - Health risks, social relations and class: an analysis of occupational health discourse in Finnish newspaper and women's magazine articles 1961-2008. AB - In this article we examine the treatment of psychosocial risks in public occupational health discourse in Finnish newspaper and magazine articles between the 1960s and 2000s, using discourse analysis. Building on class theories, our aim is to investigate how class expectations have been linked with the redefinition of occupational health risks during this period. Our results suggest that as social relations at the workplace became problematised in the occupational health discussions after the 1970s, the image of the hierarchical and naturally conflictual organisation was replaced by idealised middle-class notions of smoothly functioning, harmonious organisations that offered rewarding work experiences. However, this same period since the late 1970s has also been characterised by increasing economic competition and neoliberal market ideology. We conclude that the concern about work-related psychosocial risks and health problems expressed in Finnish newspaper and magazine articles during the last three decades has been shaped in many respects by a collision between the dominant middle-class expectations of harmony and equality and the neoliberal production of competition and inequality. PMID- 26547281 TI - Landscape genetics in a changing world: disentangling historical and contemporary influences and inferring change. AB - Landscape genetics seeks to determine the effect of landscape features on gene flow and genetic structure. Often, such analyses are intended to inform conservation and management. However, depending on the many factors that influence the time to reach equilibrium, genetic structure may more strongly represent past rather than contemporary landscapes. This well-known lag between current demographic processes and population genetic structure often makes it challenging to interpret how contemporary landscapes and anthropogenic activity shape gene flow. Here, we review the theoretical framework for factors that influence time lags, summarize approaches to address this temporal disconnect in landscape genetic studies, and evaluate ways to make inferences about landscape change and its effects on species using genetic data alone or in combination with other data. Those approaches include comparing correlation of genetic structure with historical versus contemporary landscapes, using molecular markers with different rates of evolution, contrasting metrics of genetic structure and gene flow that reflect population genetic processes operating at different temporal scales, comparing historical and contemporary samples, combining genetic data with contemporary estimates of species distribution or movement, and controlling for phylogeographic history. We recommend using simulated data sets to explore time lags in genetic structure, and argue that time lags should be explicitly considered both when designing and interpreting landscape genetic studies. We conclude that the time lag problem can be exploited to strengthen inferences about recent landscape changes and to establish conservation baselines, particularly when genetic data are combined with other data. PMID- 26547282 TI - Eco-morphological differentiation in Lake Magadi tilapia, an extremophile cichlid fish living in hot, alkaline and hypersaline lakes in East Africa. AB - Ecological diversification through divergent selection is thought to be a major force during the process of adaptive radiations. However, the large sizes and complexity of most radiations such as those of the cichlids in the African Great Lakes make it impossible to infer the exact evolutionary history of any population divergence event. The genus Alcolapia, a small cichlid lineage endemic to Lakes Magadi and Natron in East Africa, exhibits phenotypes similar to some of those found in cichlids of the radiations of the African Great Lakes. The simplicity within Alcolapia makes it an excellent model system to investigate ecological diversification and speciation. We used an integrated approach including population genomics based on RAD-seq data, geometric morphometrics and stable isotope analyses to investigate the eco-morphological diversification of tilapia in Lake Magadi and its satellite lake Little Magadi. Additionally, we reconstructed the demographic history of the species using coalescent simulations based on the joint site frequency spectrum. The population in Little Magadi has a characteristically upturned mouth--possibly an adaptation to feeding on prey from the water surface. Eco-morphological differences between populations within Lake Magadi are more subtle, but are consistent with known ecological differences between its lagoons such as high concentrations of nitrogen attributable to extensive guano deposits in Rest of Magadi relative to Fish Springs Lagoon. All populations diverged simultaneously only about 1100 generations ago. Differences in levels of gene flow between populations and the effective population sizes have likely resulted in the inferred heterogeneous patterns of genome-wide differentiation. PMID- 26547283 TI - Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes. AB - For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers--polycaprolactone and poly(glycerol monostearate-co-caprolactone)--to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ~90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection. PMID- 26547284 TI - How Can Mutations Thermostabilize G-Protein-Coupled Receptors? AB - Structures of over 30 different G-protein-coupled receptors (GPCRs) have advanced our understanding of cell signaling and have provided a foundation for structure guided drug design. This exciting progress has required the development of three complementary methods to facilitate GPCR crystallization, one of which is the thermostabilization of receptors by systematic mutagenesis. However, the reason why a particular mutation, or combination of mutations, stabilizes the receptor is not always evident from a static crystal structure. Molecular dynamics (MD) simulations have been used to identify and estimate the energetic factors that affect thermostability through comparing the dynamics of the thermostabilized receptors with structure-based models of the wild-type receptor. The data indicate that receptors are stabilized through a combination of factors, including an increase in receptor rigidity, a decrease in collective motion, reduced stress at specific residues, and the presence of ordered water molecules. Predicting thermostabilizing mutations computationally represents a major challenge for the field. PMID- 26547285 TI - Risk factors for venous thromboembolism after pediatric trauma. AB - BACKGROUND/PURPOSE: The purposes of this study were to identify independent predictors of venous thromboembolism (VTE), to evaluate the relative impact of adult VTE risk factors, and to identify a pediatric population at high-risk for VTE after trauma. METHODS: 1934 consecutive pediatric admissions (<= 17 years) from 01/2000 to 12/2012 at a level 1 trauma center were reviewed. Logistic regression was used to identify predictors of VTE. RESULTS: Twenty-two patients (1.2%) developed a VTE, including 5% of those requiring orthopedic surgery, 14% of those with major vascular injury (MVI), and 36% of those with both. Most (84%) were diagnosed at the primary site of injury. 86% of those who developed a VTE were receiving thromboprophylaxis at the time of diagnosis. Independent predictors were age (odds ratio (OR): 1.59, 95% confidence interval (CI): 1.11 2.25), orthopedic surgery (OR: 8.10, CI: 3.10-21.39), transfusion (OR: 3.37, CI: 1.26-8.99), and MVI (OR: 15.43, CI: 5.70-41.76). When known risk factors for VTE in adults were adjusted, significant factors were age >= 13 years (OR: 9.16, CI: 1.08-77.89), indwelling central venous catheter (OR: 4.41, CI: 1.31-14.82), orthopedic surgery (OR: 6.80, CI: 2.47-18.74), and MVI (OR: 14.41, CI: 4.60 45.13). CONCLUSION: MVI and orthopedic surgery are synergistic predictors of pediatric VTE. Most children who developed a VTE were receiving thromboprophylaxis at the time of diagnosis. PMID- 26547286 TI - The morbidity of a divided stoma compared to a loop colostomy in patients with anorectal malformation. AB - PURPOSE: Loop colostomies may contaminate the genitourinary (GU) tract in patients with anorectal malformations (ARM) owing to incomplete diversion of stool. Stoma complications are also thought to be higher with a loop versus divided colostomy. We sought to compare the morbidity, including urinary tract infections (UTI), in these two types of colostomies in children with ARM. METHODS: A review was performed at a children's hospital (1989-2014). Children with ARM who had a colostomy performed were identified. Demographic data and outcome variables were collected. Analyses included Student's t-test, Fischer's exact and logistic regression as appropriate. RESULTS: 171 patients were identified (loop=78; divided=93). Thirty percent of patients with a divided colostomy and 24% with a loop experienced a stoma complication (p=0.5). A subgroup analysis of children with a rectourinary fistula (54 divided, 26 loop) was performed to assess for effect of colostomy type on UTI. After controlling for other UTI risk factors (major GU anomalies, vesicostomy, and prophylactic antibiotics), loop ostomies were not associated with risk of UTI (OR 0.83, 95% CI 0.27-2.63). No patient with a loop colostomy developed megarectum. CONCLUSIONS: Children with ARM who undergo a loop colostomy are not at a detectable increased risk of experiencing a UTI compared to a divided stoma. The rate of stoma complication is high regardless of the type of stoma created. PMID- 26547287 TI - Nonoperative treatment of acute appendicitis in children: A feasibility study. AB - PURPOSE: Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children. METHODS: Children 5 18 years with <48 h symptoms of acute appendicitis were offered nonoperative treatment: 2 doses of piperacillin IV, then ampicillin/clavulanate *1 week. Treatment failure (worsening on therapy) and recurrence (after completion of therapy) were noted. Patients who declined enrollment were asked to participate as controls. Cost-utility analysis was performed using Pediatric Quality of Life Scale (PedsQL(r)) to calculate quality-adjusted life month (QALM) for study and control patients. RESULTS: Twenty-four patients agreed to undergo nonoperative management, and 50 acted as controls. At a mean follow-up of 14 months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52 days, respectively. Two patients elected to undergo an interval appendectomy despite absence of symptoms. Appendectomy-free rate at one year was therefore 71% (C.I. 50-87%). No patient developed perforation or other complications. Cost utility analysis shows a 0.007-0.03 QALM increase and a $1359 savings from $4130 to $2771 per nonoperatively treated patient. CONCLUSION: Despite occasional late recurrences, antibiotic-only treatment of early appendicitis in children is feasible, safe, cost-effective and is experienced more favorably by patients and parents. PMID- 26547288 TI - Right atrial thrombosis: Beware the patent foramen ovale. PMID- 26547289 TI - Commentary: Clinical evaluation of a two-incision fistula technique for the treatment of oral ranulas. PMID- 26547290 TI - Double-barrelled vascularised fibular free flap using computer-assisted preoperative planning and a surgical template for accurate reconstruction of a segmental mandibular defect. PMID- 26547291 TI - A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk. AB - Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated. PMID- 26547292 TI - Use of Mechanical Circulatory Support in Percutaneous Coronary Intervention in the United States. AB - Percutaneous ventricular assist devices (PVADs) and intraaortic balloon pump (IABP) are used to provide mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI). Contemporary trends in their utilization and impact on in-hospital mortality are not known. Using the National Inpatient Sample (2004 to 2012), we identified 5,031 patients who received a PVAD and 122,333 who received an IABP on the same day as PCI using International Classification of Diseases, Ninth Edition codes. Utilization of MCS increased from 1.3% of all PCIs in 2004 to 3.4% in 2012 (p trend <0.001), with increase in the use of both PVAD (<1/10,000 PCIs [2004 to 2007] to 38/10,000 [2012]) and IABP (132/10,000 PCIs [2004] to 299/10,000[2012] p <0.0001 for both). PVAD recipients were older (69 vs 65 years), more likely to have heart failure (68% vs 41%), chronic kidney disease (27% vs 11%, p <0.001 for all), and be admitted electively (30% vs 11%), but less likely to have acute myocardial infarction (52% vs 90%), cardiogenic shock (23% vs 50%), or need mechanical ventilation (16% vs 29%) compared with IABP recipients. Unadjusted in-hospital mortality was lower in PVAD compared with IABP recipients (12.8% vs 20.9%, p <0.001). However, in propensity matched analyses (1:2), in-hospital mortality was similar in both groups (odds ratio 0.88, 95% confidence interval 0.70 to 1.09). In conclusion, there has been a marked increase in the utilization of MCS in patients undergoing PCI. Unadjusted mortality using PVADs is lower than IABP but may be due to their selective use in patients at lower risk. Randomized trials are necessary to establish their effectiveness in supporting high-risk PCI. PMID- 26547294 TI - C9orf72 expansion presenting as an eating disorder. AB - This report describes a 64-year-old woman with a strong family history of motor neuron disease, whose diagnosis of behavioural variant frontotemporal dementia was delayed due to her initial presentation with atypical manifestations, including restriction of oral intake resulting in low weight, disordered eating and anxiety. Upon investigation, she was found to be a carrier of the C9orf72 hexanucleotide repeat expansion. Our case supports previous publications asserting that C9orf72 mutation carriers manifest with diverse clinical syndromes, and expands the phenotype to include anorexia and food refusal as potential features of the condition. PMID- 26547293 TI - Target-controlled infusion of remifentanil with or without flurbiprofen axetil in sedation for extracorporeal shock wave lithotripsy of pancreatic stones: a prospective, open-label, randomized controlled trial. AB - BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is an effective therapeutic method used to treat patients with pancreatic stones. However, the anesthesia for this procedure has been underappreciated, with minimal reports of these procedures in certain case series with general or epidural anesthesia. METHODS: A cohort of 60 patients who elected to undergo ESWL in order to treat pancreatic stones for the first time were randomly selected and divided into two groups. One group of patients received target controlled infusion (TCI) of remifentanil, while the other group of patients received TCI of remifentanil plus a bolus of flurbiprofen axetil (a cyclooxygenase inhibitor) (Rem group and Rem + Flu group, n = 30 for each group). The Dixon's up-and-down method was used to calculate the half maximum effective concentration (EC50) of remifentanil. Visual analogue scales of pain, Ramsay sedation scale, hemodynamic changes, and adverse events were also recorded. RESULTS: The EC50 of remifentanil was calculated to be 4.0 ng/ml (95 % confidential interval: 3.84 ng/ml, 4.16 ng/ml) and 2.76 ng/ml (95 % confidential interval: 2.63 ng/ml, 2.89 ng/ml) in the Rem group and Rem + Flu group respectively (p < 0.001). Pain score was comparable between the two groups, while the Ramsay sedation scale was higher in the Rem group. Hemodynamic data showed that patients in the Rem group experienced higher mean arterial pressures and higher heart rates across the procedures. Patients in Rem group demonstrated a lower respiratory rate (p < 0.001) and a lower SpO2 (p = 0.001). Less adverse events occurred in Rem + Flu group, including a reduced respiratory depression requiring wake-up as well as reduced postoperative nausea and vomiting. CONCLUSION: Remifentanil plus flurbiprofen axetil provided satisfactory analgesia and sedation for ESWL of pancreatic stones with less adverse events. (Clinicaltrial.gov: NCT01998217 ; registered on November 19, 2013). PMID- 26547295 TI - Hemorrhage in astroblastoma: An unusual manifestation of an extremely rare entity. AB - Astroblastoma is a rare tumor of glial origin with characteristics of both astrocytoma and ependymoma. It is usually seen in children and young adults, and is peripherally located, well circumscribed, of solid-cystic composition and with heterogeneous contrast enhancement. Histopathology reveals perivascular pseudorosette formation and thick hyalinised vessels. Hemorrhage in astroblastoma is unusual and rarely described in literature. We report two patients with astroblastoma who presented with hemorrhage and discuss the natural history, radiological findings, pathophysiology of hemorrhage and histopathological characteristics. We emphasize the importance of early suspicion in peripherally located lesions with bleeding. PMID- 26547296 TI - A UPLC-MSMS method for the analysis of olanzapine in serum-with particular emphasis on drug stability testing. AB - A method including a rapid and automated extraction of olanzapine from serum followed by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed and validated. Serum aliquots (100MUL) and internal standard (olanzapine-d3, 25MUL) were pipetted onto an Ostro(TM) 96-well filtration plate and protein precipitated with acidic acetonitrile (300MUL) before removal of endogenous phospholipids by filtration followed by analysis. Chromatography was achieved using an HSST 3 (2.1*100mm, 1.8MUm) column and gradient elution with acidic water in combination with methanol at a flow rate of 0.5mL/min. The runtime was 1.5min. The mass spectrometer was monitored in positive mode and multiple reaction monitoring (MRM). The m/z 313.1>256.1 and 313.1>198.0 transitions were monitored for olanzapine (m/z 316.1>256.1 for olanzapine-d3). The quadratic calibration curves ranged from 5 to 500nM (R(2)>=0.999). Limit of quantification was 0.5nM (CV 9.6%, accuracy 110%). Within assay and between-assay inaccuracies were 2.6-11.9% (CV<=4.8%). Recovery was 84 95% (CV<=1.4%) and matrix effects ranged from 100 to 103% (CV<=2.6%). Extensive stability testing showed that at ambient temperature, olanzapine in patient serum samples were stable for at least seven hours on the laboratory bench and for at least 48h in darkness. When exposed to 3000lux, however, significant degradation had occurred after 48h. Notably, olanzapine in spiked serum was unstable already after four hours when exposed to 3000 lux. At 4-8 degrees C and exposure to 550lux, both patient serum and spiked serum were stable for more than 48h but less than a week, whereas in darkness, the samples were stable for at least 14 days. The cumulative light exposure causing significant degradation of olanzapine in patient serum was 50,000-100,000lux-h. In some individual samples, however, the effect of light exposure was more pronounced. Therefore, it seems pertinent to recommend protecting all samples from light, although we found no indication that a few hours of exposure to standard indoor illumination will affect the olanzapine concentration to any significant degree. PMID- 26547297 TI - Development and validation of impurity-profiling UPLC method for the determination of sodium cromoglicate and tetryzoline hydrochloride: Application on rabbit aqueous humor. AB - Sodium cromoglicate (SCG), antihistaminic agent, and tetryzoline hydrochloride (TZH), a sympathomimetic agent, are formulated together as an ophthalmic preparation. An ultra-performance liquid chromatographic method with UV detection (UPLC-UV) was developed and validated for the quantitative determination of SCG and TZH in rabbit aqueous humor. Due to the instability of both SCG and TZH under alkaline conditions, the UPLC method was applied for their determination in the presence of their possible degradation impurities. The separation was performed using C18 column (1.7MUm particle size) and isocratic elution system with methanol: 1% o-phosphoric acid (65: 35, v/v).The optimum flow rate was 0.5ml/min and the detection was done at 230nm. The suggested method was validated in compliance with the ICH guidelines and was successfully applied for determination of sodium cromoglicate (SCG) and tetryzoline HCl (TZH) as prepared synthetically in laboratory mixtures, and in the presence of their alkali-induced degradation impurities. The suggested method was effectively applied the determination of spiked rabbit aqueous humor samples as well as commercial pharmaceutical formulation. PMID- 26547298 TI - Sleep, Fatigue, and Problems With Cognitive Function in Adults Living With HIV. AB - Up to 50% of people living with HIV have some neurocognitive impairment. We examined associations of sleep and fatigue with self-reported cognitive problems in 268 adults living with HIV. Multivariate regression was used to examine associations between cognitive problems, self-reported sleep quality, actigraphy measured total sleep time and wake after sleep onset, and fatigue severity. Poorer self-reported sleep quality (p < .001), short or long total sleep time (<7 or >8 vs. 7-8 hours, p = .015), and greater fatigue (p < .001) were associated with lower self-reported cognitive function scores after controlling for demographic and clinical characteristics. However, objective measure of wake after sleep onset was unrelated to self-reported cognitive function scores. Findings suggest that assessing and treating poor sleep and complaints about fatigue would be areas for intervention that could have a greater impact on improving cognition function than interventions that target only cognitive problems. PMID- 26547299 TI - Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession? AB - BACKGROUND: Direct evidence of the effect of drug seizures on drug use and drug related harm is fairly sparse. The aim of this study was to see whether seizures of heroin, cocaine and ATS predict the number of people arrested for use and possession of these drugs and the number overdosing on them. METHOD: We examined the effect of seizure frequency and seizure weight on arrests for drug use and possession and on the frequency of drug overdose with autoregressive distributed lag (ARDL) models. Granger causality tests were used to test for simultaneity. RESULTS: Over the short term (i.e. up to 4 months), increases in the intensity of high-level drug law enforcement (as measured by seizure weight and frequency) directed at ATS, cocaine and heroin did not appear to have any suppression effect on emergency department (ED) presentations relating to ATS, cocaine and heroin, or on arrests for use and/or possession of these drugs. A significant negative contemporaneous relationship was found between the heroin seizure weight and arrests for use and/or possession of heroin. However no evidence emerged of a contemporaneous or lagged relationship between heroin seizures and heroin ED presentations. CONCLUSION: The balance of evidence suggests that, in the Australian context, increases in the monthly seizure frequency and quantity of ATS, cocaine and heroin are signals of increased rather than reduced supply. PMID- 26547300 TI - Alcohol consumption in the Arab region: What do we know, why does it matter, and what are the policy implications for youth harm reduction? AB - Alcohol is a recognized global risk factor for many diseases and injury types and a major contributor to disability and death. While cost-effective interventions do exist, many countries lack a comprehensive national alcohol harm reduction policy. The Arab world includes 22 diverse countries stretching from North Africa to Western Asia having varying dispositions with regards to alcohol sale and consumption. Epidemiological data is scattered and the picture on alcohol consumption remains blurry. This paper presents the findings of an extensive review conducted on all 22 Arab countries, specifically describing: (1) the density and methodology of alcohol-related peer-reviewed publications over the last two decades (1993-2013); (2) the epidemiology of alcohol consumption given all available data; and (3) the current status of policies in the region. Our search revealed a strikingly low number of alcohol-related peer-reviewed published studies - a total of 81 publications across 22 countries and two decades. Most studies are based on clinical or student samples. Where data is available, age of onset is low and drinking is frequent, in the absence of any available or enforced harm reduction policies. We submit that countries in the Arab region can be divided into four categories by alcohol ban and published data. One category includes countries where alcohol is not banned but data is absent, suggesting an ostrich-like response to a controversial behavior, or reflecting a weak research infrastructure and/or policy landscape. Evidence informed recommendations and future directions for policy and research are discussed and tailored to countries' current stance on alcohol legislation and consumption. Given the particular vulnerability of youth to uptake of alcohol as well as the resulting short and long term consequences, the paper concludes by focusing on the implications of the findings for youth alcohol harm reduction. PMID- 26547301 TI - How to assess success of treatment when using multiple doses: the case of misoprostol for medical abortion. AB - BACKGROUND: The assessment of treatment success in clinical trials when multiple (repeated) doses (courses) are involved is quite common, for example, in the case of infertility treatment with assisted reproductive technology (ART), and medical abortion using misoprostol alone or in combination with mifepristone. Under these or similar circumstances, most researchers assess success using binomial proportions after a certain number of consecutive doses, and some have used survival analysis. In this paper we discuss the main problems in using binomial proportions to summarize (the overall) efficacy after two or more consecutive doses of the relevant treatment, particularly for the case of misoprostol in medical abortion studies. We later discuss why the survival analysis is best suited under these circumstances, and illustrate this by using simulated data. METHODS: The formulas required for the binomial proportion and survival analysis (without and with competing risks) approaches are summarized and analytically compared. Additionally, numerical results are computed and compared between the two approaches, for several theoretical scenarios. RESULTS: The main conceptual limitations of the binomial proportion approach are identified and discussed, caused mainly by the presence of censoring and competing risks, and it is demonstrated how survival analysis can solve these problems. In general, the binomial proportion approach tends to underestimate the "real" success rate, and tends to overestimate the corresponding standard error. CONCLUSIONS: Depending on the rates of censored observations or competing events between repeated doses of the treatment, the bias of the binomial proportion approach as compared to the survival analysis approaches varies; however, the use of the binomial approach is unjustified as the survival analysis options are well known and available in multiple statistical packages. Our conclusions also apply to other situations where success is estimated after multiple (repeated) doses (courses) of the treatment. PMID- 26547302 TI - Evaluating vision-related quality of life in preoperative age-related cataract patients and analyzing its influencing factors in China: a cross-sectional study. AB - BACKGROUND: To evaluate vision-related quality of life in preoperative age related cataract patients in China, using the Chinese version of the National Eye Institute Visual Function Questionnaire-25 (CHI-NEI-VFQ-25), together with analyses of its influencing factors. METHODS: Cataract patients were interviewed using the CHI-NEI-VFQ-25, and their demographic information was recorded. The Cronbach alpha coefficient was used to determine the internal consistency of the CHI-NEI-VFQ-25. Multi-trait analyses were used to assess construct validity, including item convergent validity and item discriminant validity. The data were evaluated by descriptive statistical analyses, by the Kruskal-Wallis rank sum test, and by multinomial logistic regression. RESULTS: The Cronbach alpha coefficients were all above 0.8, except for the driving subscale. All items passed the convergent and discriminant validity tests. The composite score was 63.0. The lowest five subscale scores were in general vision (40.0), mental health (37.5), role difficulty (37.5), near vision activities (50.0), and dependence (58.3). Except for the subscale scores of general health and ocular pain, the composite scores and subscale scores were positively associated with the best-corrected visual acuity (BCVA) in the better eye. Multinomial logistic regression showed that sex, age, and educational attainment were significantly associated with the composite score and subscale scores. CONCLUSIONS: BCVA in the better eye was the most important determinant associated with the decrease in vision-related quality of life. Visual impairment had more impact on the psychosocial parameter than on the other parameters of the patients' quality of life. Among all the demographic characteristics, including sex, age, and educational attainment, influenced the quality of life in age-related cataract patients. PMID- 26547303 TI - Translating person-centered care into practice: A comparative analysis of motivational interviewing, illness-integration support, and guided self determination. AB - OBJECTIVE: Person-centred care [PCC] can engage people in living well with a chronic condition. However, translating PCC into practice is challenging. We aimed to compare the translational potentials of three approaches: motivational interviewing [MI], illness integration support [IIS] and guided self determination [GSD]. METHODS: Comparative analysis included eight components: (1) philosophical origin; (2) development in original clinical setting; (3) theoretical underpinnings; (4) overarching goal and supportive processes; (5) general principles, strategies or tools for engaging peoples; (6) health care professionals' background and training; (7) fidelity assessment; (8) reported effects. RESULTS: Although all approaches promoted autonomous motivation, they differed in other ways. Their original settings explain why IIS and GSD strive for life-illness integration, whereas MI focuses on managing ambivalence. IIS and GSD were based on grounded theories, and MI was intuitively developed. All apply processes and strategies to advance professionals' communication skills and engagement; GSD includes context-specific reflection sheets. All offer training programs; MI and GSD include fidelity tools. CONCLUSION: Each approach has a primary application: MI, when ambivalence threatens positive change; IIS, when integrating newly diagnosed chronic conditions; and GSD, when problem solving is difficult, or deadlocked. PRACTICE IMPLICATIONS: Professionals must critically consider the context in their choice of approach. PMID- 26547304 TI - The Conversations About Cancer (CAC) Project-Phase II: National findings from viewing When Cancer Calls...and implications for Entertainment-Education (E-E). AB - OBJECTIVE: We address cancer communication by creating and assessing the impacts of a theatrical production, When Cancer Calls...(WCC...), anchored in conversations from the first natural history of a patient and family members talking through cancer on the telephone. METHODS: A national study was conducted using a multi-site and randomized controlled trial. An 80-minute video was produced to assess viewing impacts across cancer patients, survivors, and family members. Comparisons were made with a control video on cancer nutrition and diet. Pretest-posttest sample size was 1006, and 669 participants completed a 30-day follow-up impacts assessment. RESULTS: All five family and communication indices increased significantly for WCC.... When compared to the placebo, average pretest posttest change scores were higher for self-efficacy (775%), family fabric (665%), outside support (189%), and family communication (97%). One month following viewings, WCC...participants reported 30% more conversations about cancer among patients and family members about cancer. CONCLUSION: A new genre of Entertainment-Education (E-E) was created that triggers positive reactions from audience members. Managing delicate and often complex communication about the trials, tribulations, hopes, and triumphs of cancer journeys is fundamentally important for everyday living. PRACTICE IMPLICATIONS: Unique opportunities exist to make WCC... available to national and global audiences, create tailored curricula, and integrate these viewings into educational programs for patients, family members, and care-provider teams across diverse health, corporate, and governmental systems. PMID- 26547305 TI - Jews, Creativity and the Genius of Disobedience. AB - Jews comprise less than one percent of the world's population; however, in the second half of the twentieth century and in the twenty-first century Jews have been awarded more than 25 % of the Nobel Prizes. Why are Jews so creative? Some have claimed, they are genetically more intelligent as determined by IQ tests. Whereas there is an intelligence threshold people must reach before being highly creative after this threshold is reached there is no strong relationship between creativity and intelligence. Creative innovation is heavily dependent upon disengagement and divergent thinking as well as subsequent convergent thinking and productivity. The mean by which a person's brain functions is dependent upon both nature (genetically determined) and nature (learned). In regard to nature, from their earliest age many Jewish children are encouraged to question as well as taught that disobedience in the pursuit of truth and justice is not only justified but is also desirable. Thus, disobedience in this regard is not the cultivation of insolence, but rather gives rise to disengagement and divergent thinking, the critical elements of creativity.Training can also alter the brain, and the Jewish people success in creativity may not be related to their genetically determined IQ, but rather the learned propensity to earnestly question and seek better alternatives. PMID- 26547306 TI - Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation. AB - BACKGROUND: The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. METHODS: Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. RESULTS: Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. CONCLUSION: The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions. PMID- 26547307 TI - Realising the Value of Linked Data to Health Economic Analyses of Cancer Care: A Case Study of Cancer 2015. AB - There is a growing appetite for large complex databases that integrate a range of personal, socio-demographic, health, genetic and financial information on individuals. It has been argued that 'Big Data' will provide the necessary catalyst to advance both biomedical research and health economics and outcomes research. However, it is important that we do not succumb to being data rich but information poor. This paper discusses the benefits and challenges of building Big Data, analysing Big Data and making appropriate inferences in order to advance cancer care, using Cancer 2015 (a prospective, longitudinal, genomic cohort study in Victoria, Australia) as a case study. Cancer 2015 has been linked to State and Commonwealth reimbursement databases that have known limitations. This partly reflects the funding arrangements in Australia, a country with both public and private provision, including public funding of private healthcare, and partly the legislative frameworks that govern data linkage. Additionally, linkage is not without time delays and, as such, achieving a contemporaneous database is challenging. Despite these limitations, there is clear value in using linked data and creating Big Data. This paper describes the linked Cancer 2015 dataset, discusses estimation issues given the nature of the data and presents panel regression results that allow us to make possible inferences regarding which patient, disease, genomic and treatment characteristics explain variation in health expenditure. PMID- 26547308 TI - When does colonisation of a semi-arid hillslope generate vegetation patterns? AB - Patterned vegetation occurs in many semi-arid regions of the world. Most previous studies have assumed that patterns form from a starting point of uniform vegetation, for example as a response to a decrease in mean annual rainfall. However an alternative possibility is that patterns are generated when bare ground is colonised. This paper investigates the conditions under which colonisation leads to patterning on sloping ground. The slope gradient plays an important role because of the downhill flow of rainwater. One long-established consequence of this is that patterns are organised into stripes running parallel to the contours; such patterns are known as banded vegetation or tiger bush. This paper shows that the slope also has an important effect on colonisation, since the uphill and downhill edges of an isolated vegetation patch have different dynamics. For the much-used Klausmeier model for semi-arid vegetation, the author shows that without a term representing water diffusion, colonisation always generates uniform vegetation rather than a pattern. However the combination of a sufficiently large water diffusion term and a sufficiently low slope gradient does lead to colonisation-induced patterning. The author goes on to consider colonisation in the Rietkerk model, which is also in widespread use: the same conclusions apply for this model provided that a small threshold is imposed on vegetation biomass, below which plant growth is set to zero. Since the two models are quite different mathematically, this suggests that the predictions are a consequence of the basic underlying assumption of water redistribution as the pattern generation mechanism. PMID- 26547309 TI - Comment on Pharmacokinetic Studies in Neonates: The Utility of an Opportunistic Sampling Design. PMID- 26547310 TI - Author's Reply to Standing et al. Pharmacokinetic Studies in Neonates: The Utility of an Opportunistic Sampling Design. PMID- 26547311 TI - Cytological accuracy and radiological staging in patients with thyroid cancer in Glasgow. AB - To assess the accuracy of initial combined cytological accuracy and radiological staging of patients suspected of having thyroid malignancy with their final histopathology. Retrospective case series in a tertiary referral centre for head and neck malignancy. All patients with malignant thyroid cytology and cytology suspicious for malignancy, between the dates of June 2010 and July 2014, were included. The pre-operative staging was compared against the final histological staging. Demographics and outcomes for each patient were recorded. Sixty-five patients were recorded in this group. 20 (30.7 %) were male. The mean age at presentation was 51 years (SD 16.8 years). 39 (60 %) patients were aged over 45 years. Fine needle aspiration cytology (FNAC) was performed in all patients and was Thy 4 in 40 (62 %) and Thy 5 in 25 (38 %). Following surgery or subsequent biopsy, FNAC was found to be accurate in 38/40 (Thy 4) and 25/25 (Thy 5) cases in diagnosing malignancy, with Thy 4 yielding 95 % malignancy and Thy 5 % 100 %. Fifty-eight patients underwent a surgical procedure for thyroid cancer. Two further patients had a diagnostic hemi-thyroidectomy for later proven benign disease. Five patients due to medical co morbidities, inoperable disease or refusal of surgery were managed non-surgically. In the surgical group 16 patients underwent a diagnostic hemi-thyroidectomy and 11 of these required a completion thyroidectomy. Forty-six patients underwent total thyroidectomy. Forty-six patients underwent a neck dissection: 27 prophylactic central compartment neck dissections and 19 planned therapeutic neck dissections were performed. Radiological staging correctly predicted final pathological TNM staging in 25 (43 %) patients. 27 (47 %) patients had radiological staging which under staged their final histological staging and 6 (10 %) patients had scans that over staged their cancer. Of those that were under staged, 15 (56 %) had their nodal disease under staged (following prophylactic central neck dissection). Radiological staging comprised ultrasound (n = 58) and CT scanning (n = 45/58 pre-operatively). Pre operative staging in thyroid cancer should include cytology, ultrasound and CT scanning. Unless low-risk papillary thyroid cancer is suspected pre-operatively, patients with Thy 4 cytology can be given the offer of a total thyroidectomy as surgical management. PMID- 26547312 TI - Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma. AB - The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors. PMID- 26547313 TI - Left medial orbitofrontal cortex volume correlates with skydive-elicited euphoric experience. AB - The medial orbitofrontal cortex has been linked to the experience of positive affect. Greater medial orbitofrontal cortex volume is associated with greater expression of positive affect and reduced medial orbital frontal cortex volume is associated with blunted positive affect. However, little is known about the experience of euphoria, or extreme joy, and how this state may relate to variability in medial orbitofrontal cortex structure. To test the hypothesis that variability in euphoric experience correlates with the volume of the medial orbitofrontal cortex, we measured individuals' (N = 31) level of self-reported euphoria in response to a highly anticipated first time skydive and measured orbitofrontal cortical volumes with structural magnetic resonance imaging. Skydiving elicited a large increase in self-reported euphoria. Participants' euphoric experience was predicted by the volume of their left medial orbitofrontal cortex such that, the greater the volume, the greater the euphoria. Further analyses indicated that the left medial orbitofrontal cortex and amygdalo hippocampal complex independently explain variability in euphoric experience and that medial orbitofrontal cortex volume, in conjunction with other structures within the mOFC-centered corticolimbic circuit, can be used to predict individuals' euphoric experience. PMID- 26547314 TI - Preparation and characterization of silk fibroin/oligochitosan nanoparticles for siRNA delivery. AB - siRNA therapy offers hope treating diseases caused by genetic defects as well as viral infections and cancers, although it has been limited by the low stability of siRNA and its rapid degradation in the presence of nucleases as well as its low cellular uptake. In this study, oligochitosan (OC) combined with silk fibroin (SF) was formulated and proposed as a novel carrier for siRNA. The obtained SF/OC/siRNA nanoparticles (NPs) were characterized according to their physicochemical properties, such as their size, zeta potential, loading efficiency, stability, cytotoxicity, cellular uptake and transfection efficiency, and their properties were compared with those of OC polyplexes. The mean diameter of SF/OC/siRNA NPs was not significantly different compared to polyplexes, and the particle size ranged between 250 and 450 nm. Increased amounts of SF in NPs enhanced their loading efficiency, and NPs showed excellent stability in the presence of FBS and heparin compared with OC polyplexes. Additionally, MTT assays demonstrated that SF/OC/siRNA NPs had lower cytotoxicity. NPs showed better gene silencing with or without FBS, which could be attributed to increased loading efficiency, serum stability and cellular uptake. These properties suggest that SF/OC/siRNA NPs have a strong potential as gene carriers. PMID- 26547315 TI - Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir. AB - Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-alpha (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir. PMID- 26547316 TI - Optimizing the therapeutic efficacy of cisplatin PEGylated liposomes via incorporation of different DPPG ratios: In vitro and in vivo studies. AB - The anionic lipid DPPG is known to enhance the cellular uptake of liposomes by forming phase boundaries of high fusogenic potentials in vesicular membranes. The focus of this study is to optimize DPPG concentrations to improve the therapeutic efficacy of cisplatin-loaded liposomes. First, cisplatin liposomes composed of HSPC, mPEG2000-DSPE and cholesterol with increasing amounts of DPPG (10, 20 and 30% mol) were prepared by ethanol injection. Liposomes were then characterized by their size, zeta potential and cytotoxicity against C26 colon carcinoma cells. In an experimental system, based upon C26 tumor bearing BALB/c, mice were treated with administering i.v. doses of different formulations, once weekly for total of three weeks. Although with the highest DPPG ratio (30% mol) liposomes exhibited the highest toxicity in vitro, at 10% DPPG better stability of the encapsulated drug was obtained in the presence of serum. In addition, survival of animals was substantially improved at 10% DPPG compared to the higher DPPG contents. It is thus presumable that the high density of negatively charged residues of DPPG gave rise to repulsive forces between phospholipids in concentric lipid bilayers, which resulted in the instability of lipid structure and the subsequent premature drug leakage. Results indicated that cisplatin liposome fabricated with the inclusion of 10% DPPG, maintains the stability while in circulation, and improves therapeutic efficacy due to fusogenic properties; therefore might serve as an effective and stable formulation of cisplatin. However, further investigations are required to confirm the potential anti-tumor effects of cisplatin anionic nanoliposomes in various tumor types. PMID- 26547317 TI - N-Acetyl cysteine (NAC)-mediated reinforcement of alpha-tricalcium phosphate/silk fibroin (alpha-TCP/SF) cement. AB - Calcium phosphate cements (CPCs) are popular bone filling materials and drug carriers. However poor mechanical properties and lack of osteoinduction restrict their clinical applications. Recent studies suggested the osteogenic properties of NAC. In our study, we incorporated NAC with alpha-TCP/SF. We found that the compressive strength of alpha-TCP/SF-NAC composites increased with increase in NAC concentration, possibly due to complex three-dimensional networks of SF induced by NAC, which was large and chemically heterogeneous and induced compact oriented growth of HA crystals. However the setting time increased slightly with the addition of NAC, due to the ruptured disulfide bonds in SF. The alpha-TCP/SF NAC composites also showed decent biocompatibility in vitro. As a result, these composites hold great potential as bone filling materials for clinical applications, including minimally invasive surgeries. PMID- 26547318 TI - High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring. AB - Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny's health. Folic acid (FA) supplementation during pregnancy has decreased the incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants' brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (P < 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings' CH gene expression in a sex-specific manner. These changes may influence infants' brain development. PMID- 26547320 TI - Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of industrial effluents originated from different industrial activities. AB - Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of treated effluents originated from four types of industrial activities (two textile industries, three rubber based industries, two common treatment plants of industrial zones, and two water treatment plants) was assessed. Physico-chemical parameters including the heavy metal/metalloid levels of the effluents varied depending on the industry profile, but most of the measured parameters in the effluents were within the specified tolerance limits of Sri Lankan environmental regulations for discharge of industrial effluents into inland surface waters. In the A. cepa test system, the undiluted effluents induced statistically significant root growth retardation, mitosis depression, and chromosomal aberrations in root meristematic cells in most cases in comparison to the dilution water and upstream water signifying effluent induced cytotoxicity and genotoxicity. Ethyl methane sulphonate (a mutagen, positive control) and all the effluents under 1:8 dilution significantly induced total chromosomal aberrations in root meristematic cells in comparison to the dilution water and upstream water indicating inadequacy of expected 1:8 dilutions in the receiving waters for curtailing genotoxic impacts. The results support the use of a practically feasible A. cepa test system for rapid screening of cytotoxicity and genotoxicity of diverse industrial effluents discharging into inland surface waters. PMID- 26547319 TI - Spinal and Bulbar Muscular Atrophy Overview. AB - Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by an expanded repeat in the androgen receptor gene. The mutant protein is toxic to motor neurons and muscle. The toxicity is ligand-dependent and likely involves aberrant interaction of the mutant androgen receptor with other nuclear factors leading to transcriptional dysregulation. Various therapeutic strategies have been effective in transgenic animal models, and the challenge now is to translate these strategies into safe and effective treatment in patients. PMID- 26547321 TI - Heavy metal contamination of agricultural soils affected by mining activities around the Ganxi River in Chenzhou, Southern China. AB - Heavy metal contamination attracted a wide spread attention due to their strong toxicity and persistence. The Ganxi River, located in Chenzhou City, Southern China, has been severely polluted by lead/zinc ore mining activities. This work investigated the heavy metal pollution in agricultural soils around the Ganxi River. The total concentrations of heavy metals were determined by inductively coupled plasma-mass spectrometry. The potential risk associated with the heavy metals in soil was assessed by Nemerow comprehensive index and potential ecological risk index. In both methods, the study area was rated as very high risk. Multivariate statistical methods including Pearson's correlation analysis, hierarchical cluster analysis, and principal component analysis were employed to evaluate the relationships between heavy metals, as well as the correlation between heavy metals and pH, to identify the metal sources. Three distinct clusters have been observed by hierarchical cluster analysis. In principal component analysis, a total of two components were extracted to explain over 90% of the total variance, both of which were associated with anthropogenic sources. PMID- 26547322 TI - Effects of urban green infrastructure (UGI) on local outdoor microclimate during the growing season. AB - This study analyzed how the variations of plant area index (PAI) and weather conditions alter the influence of urban green infrastructure (UGI) on microclimate. To observe how diverse UGIs affect the ambient microclimate through the seasons, microclimatic data were measured during the growing season at five sites in a local urban area in The Netherlands. Site A was located in an open space; sites B, C, and D were covered by different types and configurations of green infrastructure (grove, a single deciduous tree, and street trees, respectively); and site E was adjacent to buildings to study the effects of their facades on microclimate. Hemispherical photography and globe thermometers were used to quantify PAI and thermal comfort at both shaded and unshaded locations. The results showed that groves with high tree density (site B) have the strongest effect on microclimate conditions. Monthly variations in the differences of mean radiant temperature (?Tmrt) between shaded and unshaded areas followed the same pattern as the PAI. Linear regression showed a significant positive correlation between PAI and ?Tmrt. The difference of daily average air temperature (?T a ) between shaded and unshaded areas was also positively correlated to PAI, but with a slope coefficient below the measurement accuracy (+/-0.5 degrees C). This study showed that weather conditions can significantly impact the effectiveness of UGI in regulating microclimate. The results of this study can support the development of appropriate UGI measures to enhance thermal comfort in urban areas. PMID- 26547324 TI - Twitter--an indispensable tool for all. PMID- 26547323 TI - Functional Properties of Grape and Wine Polyphenols. AB - Grape berries polyphenols are mainly synthesized in the skin tissues and seeds and they are extracted during the winemaking process. These substances have a potentially positive effect, on human health, thus giving to grape and red wine "functional properties" that can contribute to prevent a number of human illness. Nevertheless, the research community is showing that the real effect is a result of a combination of different factors, notably daily intake, bioavailability, or in vivo antioxidant activity that are yet to be resolved. Viticulture and winemaking practices, determine the concentration of polyphenols in grape and wine. To date, reduced knowledge is existing on the effects of different yeast strains on the final concentration of polyphenols in red wine. We summarize the recent findings concerning the effects of polyphenols on human chronic disease and the future directions for research to increase the amount of these compounds in wine. PMID- 26547325 TI - [Correlation analysis of serum calcium levels and risks of diabetes mellitus in middle-aged and elderly men]. AB - OBJECTIVE: To investigate the correlation of serum calcium levels and the risks of diabetes mellitus (DM) in middle-aged elderly men. METHODS: A total of 3386 male subjects aged 40-79 years were selected from two local communities of Beijing using stratified random sampling for this cross-sectional survey. The survey was conducted using questionnaires, and all the subjects underwent physical examination and blood tests of serum calcium, vitamin D and other biochemical parameters. The subjects were divided into normal glucose group, prediabetic group and diabetic group to compare their blood biochemical parameters and analyze the risk factors of diabetes. RESULTS: The prevalence of diabetes and pre-diabetes was 32.31% in the 3386 subjects surveyed. Serum calcium, vitamin D and Creatinine (Cr) levels were significantly higher in pre diabetic and diabetic groups than in the non-diabetic group (P/0.05), and age, body mass index, serum calcium, vitamin D, and Cr levels differed significantly between the former two groups (P/0.05). The prevalence of diabetes increased significantly with serum calcium level (P/0.05). Logistic regression analysis showed that age, body mass index, serum calcium, and serum vitamin D levels were independent risk factors for diabetes (P/0.05). CONCLUSION: Male diabetic patients have abnormal serum calcium levels. An increased age and increased serum calcium levels are associated with higher risks of diabetes, and age, serum calcium, serum vitamin D, Cr, and body mass index are all risk factors of diabetes in men. PMID- 26547326 TI - [Role of transient receptor potential canonical 1 in airway remodeling and effect of budesonide on its pulmonary expression in asthmatic guinea pigs]. AB - OBJECTIVE: To explore the role of transient receptor potential canonical 1 (TRPC1) in airway remodeling and the effect of budesonide intervention on its expression in the lungs of guinea pigs with ovalbumin-induced asthma. METHODS: Fifty male guinea pigs were randomized into 5 equal groups, including a blank control group, ovalbumin group, ovalbumin+TRPC1 siRNA group, ovalbumin+luciferase siRNA group, and ovalbumin+budesonide group. After corresponding treatments, bronchoalveolar lavage was collected from the guinea pigs for eosinophils analysis and detection of IL-5 and IL-13 levels using ELISA. The lung tissues were stained with HE and Masson's trichrome to observe the bronchial wall thickness, smooth muscle hypertrophy, subepithelial collagen deposition, and lung inflammations. Immunohistochemistry and real-time quantitative PCR were performed to detect TRPC1 protein and mRNA expressions in the lungs, respectively. RESULTS: The guinea pig models of ovalbumin-induced asthma showed significantly increased thickness of the bronchial wall, smooth muscle hypertrophy, collagen deposition and inflammatory cell infiltration, but these pathologies were obviously alleviated by treatment with TRPC1 siRNA or budesonide (P/0.05). Immunohistochemstry showed that TRPC1 protein was distributed mainly on the cell membrane and in the nuclei of the basal cells or columnar epithelial cells. CONCLUSION: The up-regulated expression of TRPC1 ion channel is closely associated with the occurrence and progression of airway remodeling and chronic airway inflammation in asthma. Budesonide can partially suppress airway remodeling and inflammation by regulating the expression of TRPC1. PMID- 26547327 TI - [Long-term outcome of patients undergoing recanalization procedures for chronic total coronary occlusion]. AB - OBJECTIVE: To compare the long-term outcomes of patients receiving percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy for treatment of chronic total coronary occlusion (CTO). METHODS: The patients with CTO were selected from a consecutive cohort of patients who underwent coronary angiography (CAG) between 2008 and 2009. The patients with multiple CAG were excluded. The patients received treatments with PCI, CABG, or conservative medication therapy and were followed for major adverse cardiovascular events (MACE) within 5 years. RESULTS: A total of 253 patients were enrolled in this study, including 192 receiving PCI, 48 receiving CABG, and 13 treated conservatively with medications. The baseline clinical characteristics were similar among the 3 groups except for increased low-density lipoprotein (LDL) and total cholesterol (TC) in the medication group, and increased Syndax score in CABG group. During the follow-up, the incidences of MACE, AMI, death, stroke or heart failure did not differ significantly among the 3 groups (P>0.05). However, CABG group showed a higher incidence of the stroke than the other two groups although this difference did not reach a statistically significantly level (P=0.06). CONCLUSION: Our study did not demonstrate that recanalization offers greater long-term benefits than medications for treatment of CTO, and the patients receiving CABG appeared to have a higher incidence of stroke. PMID- 26547328 TI - [Relationship between coronal intercondylar notch width index and osteoarthritis]. AB - OBJECTIVE: To study the relationship between knee osteoarthritis (OA) and intercondylar notch narrowing based on the notch width index. METHODS: Magnetic resonance (MR) images were collected from middle-aged and elderly patients with a definite diagnosis of knee OA, including 42 with mild OA and 37 with moderate to severe OA, with 70 healthy individuals serving as the control group. The notch width indexes NWI, NWI-A, and NWI-P on the coronal images at different levels were calculated, and the intercondylar notch was classified, according to the features on axial MR images, into types A, U, and W. The association of OA with NWI, NWI-A, NWI-P, and notch type was determined, and the cutoff values were obtained based on the ROC curves at different levels as indicators for diagnosis of intercondylar notch stenosis. RESULTS: In the control, mild OA, moderate to severe OA groups, the NWI value on coronal MR images were 0.252+/-0.019, 0.251+/ 0.017, and 0.240+/-0.020, NWI-A were 0.261+/-0.024, 0.259+/-0.023, and 0.245+/ 0.023, and NWI-P were 0.271+/-0.026, 0.270+/-0.024, and 0.254+/-0.022, respectively. Patients with moderate to severe OA had significantly smaller NWI, NWI-A, and NWI-P than the other two groups (P<0.05), and a significant association was found between NWI values at each level and the occurrence of moderate to severe OA (P<0.01). A NWI value<0.248, NWI-A<0.256, and NWI-P<0.266 supported a diagnosis of intercondylar notch narrowing. Type A intercondylar notch was found in the majority of patients with intercondylar notch narrowing (P<0.05). CONCLUSION: Patients with moderate to severe OA have significant intercondylar notch narrowing, and patients with a type A intercondylar notch are more likely to have intercondylar notch narrowing than those with type U notch. PMID- 26547329 TI - [Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvant- induced arthritis and reduced pulmonary function]. AB - OBJECTIVE: To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA). METHODS: Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments. RESULTS: Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate. CONCLUSION: Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1. PMID- 26547330 TI - [Methylglyoxal inhibits human umbilical vein cell migration in vitro by down regulating integrinbeta3]. AB - OBJECTIVE: To explore the effects of methylglyoxal on endothelia cell migration. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated by serial concentrations of methylglyoxal (MGO, 0, 25, 50, 100 and 200 umol/L) for 24 h, and the cell migration was assessed by scratch wound and Transwell assay. The expression of integrin beta3 in the treated cells was examined by immunoblotting, and the effect of an anti-beta3 antibody, LM609, on cell migration was investigated. RESULTS: Methylglyoxal significantly inhibited HUVEC migration in a concentration-dependent manner (P<0.05). Methylglyoxal decreased the expression of integrin beta3 in a time- and concentration-dependent manner (P<0.05). LM609 also significantly inhibited HUVEC migration (P<0.05). CONCLUSION: Methylglyoxal inhibits HUVEC migration in vitro by down-regulating integrin beta3 expression. PMID- 26547331 TI - [Effect of bafilomycin A1 on proliferation and oxaliplatin sensitivity in gastric cancer MGC-803 cells]. AB - OBJECTIVE: To investigate the effect of bafilomycin A1 (BAF) on the cell proliferation, invasiveness, apoptosis, and oxaliplatin sensitivity in gastric cancer MGC-803 cells. METHODS: MGC-803 cells were divided into control group, BAF group, oxaliplatin group, and BAFu oxaliplatin group. MTT assay and plate clone formation assay were used to assess the viability and colony forming ability of the cells after the treatments. The expression of nucleosomes in the cells was examined with ELISA. The cell migration and invasion after the treatments were evaluated. Western blotting was performed to detect the expression of Bcl-2 and Bax in the treated cells, and scanning electron microscopy, immunohistochemistry and Western blotting were employed to to observe the cell autophagy. RESULTS: Compared with the control cells, the cells treated with BAF showed a substantial decrease in autophagosome accumulation with attenuated cell proliferation, migration and invasion. Compared with cells treated with oxaliplatin alone, the cells treated with both BAF and oxaliplatin showed significantly lowered autophagosome accumulation, suppressed cell proliferation, migration and invasion, increased cell apoptosis, increased Bax expression and lowered Bcl-2 expression. CONCLUSION: BAF can inhibit the proliferation and invasiveness of MGC 803 cells, promote cell apoptosis by inhibiting autophagy, and enhances the sensitivity of the cells to oxaliplatin. PMID- 26547332 TI - [Establishment of a SCID beige mouse model bearing transplanted human choriocarcinoma using JAR cell line]. AB - OBJECTIVE: To establish a mouse model bearing human choriocarcinoma xenograft in severe combined immuno-deficient (SCID) beige mice and investigate the disease course and biological behaviors of the tumors. METHODS: Human choriocarcinoma JAR cells were injected in female SCID beige mice (3-5 weeks old) either subcutaneously (group A, n=6) or via the tail vein (group B, n=6). Morphological studies, radioactive immunoassay, in vivo tumor imaging and histopathological examinations were performed to confirm JAR cell engraftment at the subcutaneous injection site and in the lungs of the mice. RESULTS: On day 28 after tumor cell inoculation, the mice in group A showed palpable subcutaneous nodules, and HE staining revealed morphological features of the nodules consistent with choriocarcinoma cells; in vivo imaging in group B showed single or multiple solid tumor masses in the lungs, and tissue biopsy examination demonstrated varying degrees of tumor cell infiltration. Compared with the control mice, peripheral blood beta-HCG levels in both groups A and B increased significantly on day 14 after cell inoculation (P<0.05), and the increment was more conspicuous in group B (P<0.05). CONCLUSION: Mouse models bearing human choriocarcinoma xenograft can be successfully established by injecting JAR cells either subcutaneously or via the tail vein to mimic the characteristics of epithelial solid tumors and lung metastasis of human choriocarcinoma. PMID- 26547333 TI - [Effects of interleukin 27 and its receptor on TGFbetainduced murine pulmonary fibroblast proliferation and transformation]. AB - OBJECTIVE: To investigate the effects of interleukin-27 (IL-27) and its receptor (WSX-1) on the proliferation, transformation and collagen synthesis of the mouse lung fibroblasts. METHODS: Cultured mouse lung fibroblasts were treated with TGF beta1, recombinant murine IL-27, a IL-27 receptor (IL-27R) overexpression vector IL-27R/pCDNA3.1, IL-27 and IL-27R, or all the 3 combined. MTT assay was used to assess the proliferation of the cells, and RT-PCR and Western blotting were employed to examine the mRNA and protein expressions of a-smooth muscle actin (alpha-SMA) and types I and III collagen; immunofluorescence assay was used to test the expression and location of alpha-SMA. RESULTS: TGF-beta1 promoted the cell proliferation and obviously enhanced alpha-SMA expression and types I and III collagen synthesis in the fibroblasts. Both IL-27 and IL-27R significantly inhibited the proliferation of the pulmonary fibroblasts and obviously decreased their alpha-SMA expression and types I and III collagen synthesis, but when combined,they produced no obvious inhibitory effect on TGF-1-induced proliferation and transformation of pulmonary fibroblasts. CONCLUSION: Both IL-27 and IL-27R alone can suppress the proliferation, transformation, and collagen synthesis of mouse pulmonary fibroblasts, but their combined treatment produces no such inhibitory effect because of the neutralization of exogenous IL-27 by IL 27R to result in the failure of activating the cell signaling pathways. PMID- 26547334 TI - [Low expression of SLC22A1 is associated with a poor prognosis of hepatocellular carcinoma: analysis of 303 patients]. AB - OBJECTIVE: To evaluate the association between SLC22A1 expression and the outcomes of hepatocellular carcinoma (HCC) patients. METHODS: A tissue microarray of 303 HCC and matched adjacent noncancerous liver tissues (ANLTs) were constructed. The expression of SLC22A1 was tested by immunohistochemistry (IHC) and scored by two pathologists according to a 12-score scale (a score>6 was defined as high expression, and a score<=6 as low expression). The correlation of SLC22A1 expression with the clinicopathological features and the patients' outcome was analyzed. RESULTS: All the ANLTs had a IHC score of 12, as compared to only 29 (9.6%) of the HCC tissues. The patients were divided into 2 groups based on the IHC scores: 59% (180/303) in low expression group and 41% (123/303) in high expression group. The disease-free survival (DFS) rates and overall survival (OS) rates were significantly lower in low SLC22A1 expression group than in the high expression group. The 1-, 3-, and 5-year DFS rates were 43%, 31% and 27% in the low expression group, and were 58%, 47% and 43% in the high expression group, respectively. The 1-, 3-, and 5-year OS rates were 66%, 38% and 32% in low expression group, and were 80%, 57% and 50% in the high expression group, respectively. A low expression of SLC22A1 was positively correlated with the tumor diameter, BCLC stage, tumor differentiation, and AFP levels (P<0.05), and was an independent predictor of poor overall survival (HR=1.454; 95% CI, 1.050 2.013). CONCLUSIONS: Down-regulation of SLC22A1 is a malignant feature and a potential prognostic marker of HCC. PMID- 26547335 TI - [Effect of simulated microgravity on erythroid differentiation of K562 cells and the mechanism]. AB - OBJECTIVE: To investigate the effect of simulated microgravity on erythroid differentiation of K562 cells and explore the possible mechanism. METHODS: The fourth generation rotating cell culture system was used to generate the simulated microgravity environment. Benzidine staining was used to evaluate the cell inhibition rate, and real-time quantitative PCR (qRT-PCR) was used to detect GATA 1, GATA-2, Ets-1, F-actin, beta-Tubulin and vimentin mRNA expressions. The changes of cytoskeleton were observed by fluorescence microscopy, and Western blotting was employed to assay F-actin, beta-tubulin and vimentin protein expression levels. RESULTS: Benzidine staining showed that simulated microgravity inhibited erythroid differentiation of K562 cells. K562 cells treated with Hemin presented with increased mRNA expression of GATA-1 and reduced GATA-2 and Ets-1 mRNA expressions. Simulated microgravity treatment of the cells resulted in down regulated GATA-1, F-actin, beta-tubulin and vimentin mRNA expressions and up regulated mRNA expressions of GATA-2 and Ets-1, and reduced F-actin, beta-tubulin and vimentin protein expressions. Exposure to simulated microgravity caused decreased fluorescence intensities of cytoskeletal filament F-actin, beta-tubulin and vimentin in the cells. CONCLUSION: Simulated microgravity inhibits erythroid differentiation of K562 cells possibly by causing cytoskeleton damages to result in down-regulation of GATA-1 and up-regulation of GATA-2 and Ets-1 expressions. PMID- 26547336 TI - [Intracytoplasmic injection of morphologically selected spermatozoa from patients with male factor infertility: clinical and embryo development outcomes]. AB - OBJECTIVE: To test whether intracytoplasmic injection of morphologically selected spermatozoa (IMSI) from patients with male factor infertility can improve the clinical and embryo development outcomes of intracytoplasmic sperm injection embryo transfer (ICSI-ET). METHODS: We performed IMSI for 82 couples diagnosed with obstructive azoospermia at high magnification (*6600) and traditional ICSI for another 91 couples using testicular sperms. We also performed IMSI for 44 couples with teratozoospermia at high magnification (*6600) and traditional ICSI for 71 patients using ejaculated sperms. The clinical and embryo development outcomes were compared between the cycles. RESULTS: For obstructive azoospermia, IMSI and ICSI showed no significant difference in the rates of cleavage (95.5% vs 96.7%), D3 top quality embryos (28.2% vs 29.2%), implantation (26.4% vs 32.3%), pregnancy (47.3% vs 50%), blastocyst formation (54.3% vs 54.6%), or abortion (14% vs 7.3%) (P>0.05), but a significantly higher normal fertilization rate was achieved in IMSI group (84.3% vs 77%, P<0.05). For teratozoospermia, the 2 techniques resulted in no significant differences in the rates of cleavage (96.2% vs 95.2%), D3 top quality embryo (27.6% vs 27.1%), implantation (28.2% vs 30.7%), pregnancy (43.7% vs 43.2%), or abortion (9.7% vs 10.5%) (P>0.05), but the normal fertilization rate (68% vs 75.5%) and the blastocyst formation rate (54.6% vs 67.9% ) were significantly higher in IMSI group (P<0.05). CONCLUSION: IMSI can improve the normal fertilization rates in couples with male factor infertility (including obstructive azoospermia and teratozoospermia) and increase blastocyst formation rate in cases of azoospermia. PMID- 26547337 TI - [Protective effect of Sanhuangyinchi Fang drug serum on hydrogen peroxide-induced DNA oxidative damage in LO2 cells]. AB - OBJECTIVE: To study the protective effect of Sanhuangyinchi Fang drug serum (SF) against hydrogen peroxide-mediated DNA oxidative damage in LO2 cells. METHODS: The LO2 cells were randomly divided into the control group, H(2)O(2) group, SF groups (5%, 10%, and 15%) and vitE group. The morphological features of the treated LO2 cells were observed under inverted microscope. The viability of the treated cells was assessed with CCK-8 method, and the activity of SOD, CAT and GSH-PX were detected biochemically. Reactive oxygen species (ROS) levels, the content of 8-OHdG, and DNA damage of the cells were evaluated by flow cytometry, ELISA, and Comet assay, respectively. RESULTS: Compared with H(2)O(2) group, the cells in SF groups (10% and 15%) and vitE group showed higher cell survival rate (P<0.05) and higher SOD, CAT, GSH-PX (P<0.05) and ROS scavenging activities (P<0.01) with markedly decreases the content of 8-OHdG (P<0.01) and reduced tailing ratio, tail length, tail moment and Olive tail moment (P<0.05). CONCLUSION: SF drug serum, especially at the concentration of 15%, can protect LO2 cells from H(2)O(2)-mediated DNA oxidative damage. PMID- 26547338 TI - [Manual immunohistochemistry for detecting ALK gene fusion antibody in 519 cases of non-small lung cancer]. AB - OBJECTIVE: To investigate the expression of anaplastic lymphoma kinase (ALK) gene fusion antibody in non-small cell lung cancer (NSCLC) and explore the clinicopathological significance. METHODS: Using manual immunohistochemistry (IHC) with D5F3 rabbit monoclonal antibody, we detected the expression of ALK gene fusion protein in 519 cases of NSCLC. The relations of ALK fusion protein with the clinical characteristics of the patients and the histological classification of the tumors were analyzed. The expressions of ALK fusion protein were compared between surgical specimens and biopsy samples, and the consistency of manual IHC results was evaluated with the results of a fully automated IHC instrument and fluorescence in situ hybridization (FISH). RESULTS: The positivity rate of ALK fusion protein was 11.37% (59/519) among the cases detected by manual IHC. The patients tended to have a young age of onset (P=0.048) and most of the tumors were adenocarcinoma. In the surgical specimens, ALK fusion protein was expressed mostly in invasive mucinous adenocarcinoma (P<0.01), and it was a high risk factor of lymph node metastasis [OR=2.188(95%C.I:1.161-4.122)]. No statistical difference was found in the test results of manual IHC between surgical specimens and biopsy samples. The results by manual IHC suggesting a strong expression were consistent with the results by automated IHC and FISH. CONCLUSION: Manual IHC can be reliable for screening ALK fusion arrangement in patients with NSCLC. PMID- 26547339 TI - [Reconstruction of dynamic positron emission tomographic images by exploiting low rank and sparse penalty]. AB - OBJECTIVE: To propose a new method for dynamic positron emission tomographic (PET) image reconstruction using low rank and sparse penalty (L&S). METHODS: The L&S reconstruction model was established and the split Bregman method was used to solve the optimal cost function. The one-tissue compartment model was used to simulate a set of PET 82Rb myocardial perfusion image. The L&S reconstruction method was compared with maximum likelihood expectation maximization (MLEM) method, low-rank penalty method and sparse penalty method. RESULTS: The L&S reconstruction method had the smallest MSE and well maintained the feature information. The polar map created by L&S method was the most similar with the reference actual polar map. CONCLUSION: L&S reconstruction method is better than the other three methods in both visual and quantitative analysis of the PET images. PMID- 26547340 TI - [Construction of human Bcl-6 3'UTR reporter vector and expression vector and their functional assessment]. AB - OBJECTIVE: To observe the direct regulation of miR-127 on Bcl-6 and the effect of Bcl-6 in rescuing miR-127-induced cell cycle and cell growth inhibition. METHODS: The 3'UTR and coding region of human bcl-6 gene were amplified by PCR and cloned into pcDNA3.0-Luc and pcDNA3.0-Flag vectors, respectively. Mutations were introduced into the seed sequences of the predicted miR-127 target sites within the Bcl-6 3'UTR using recombinant PCR. Luciferase assay was used to verify the direct targeted regulation of miR-127 on Bcl-6. In HepG2 cell models with overexpression or knockdown of miR-12, the changes of cell cycle and cell growth were investigated after transfection with the constructed vectors. RESULTS: The recombinant plasmids were successfully obtained as confirmed by double digestion and sequence identification. Luciferase assay showed that in 293T and HepG2 cells, miR-127 inhibited the activation of wild-type Bcl-6 3'UTR reporter vector but not mutated Bcl-6 3'UTR vector. Overexpression of miR-127 induced cell cycle arrest at G(2)/M phase and suppressed the growth of HepG2 cells, and these effects were reversed by Bcl-6 overexpression. CONCLUSION: We successfully cloned wild-type and mutated 3'UTR reporter vectors and expression vector of bcl-6 gene and confirmed their biological functions. PMID- 26547341 TI - [Effect of bile duct ligation and recanalization on rat hepatocyte epithelial mesenchymal phenotype and NOX4 protein expression]. AB - OBJECTIVE: To observe epithelial-mesenchymal phenotypes and oxidative stress related protein expressions of the liver cells in a rat model of liver fibrosis induced by bile duct ligation and recanalization. METHODS: Twenty-four male Wistar rats were randomized into 4 groups, including a sham-operated group, two bile duct ligation groups with ligation for 2 and 4 weeks, and a bile duct ligation group with a 2-week ligation followed by a 2-week recanalization. HE staining and Masson staining were used to assess liver fibrosis in the rats, and immunohistochemistry and Western blotting were employed to detect expressions of the epithelial and mesenchymal marker proteins and oxidative stress-related proteins. RESULTS: Compared with the sham-operated group, the rats with bile duct ligation showed obvious liver fibrosis, which worsened as the ligation time extended, accompanied by significantly increased expression of alpha-SMA, collagen I, NOX(4) and vimetin and reduced E-cadherin expression. Compared with the rats with bile duct ligation for 4 weeks, the rats in bile duct ligation recanalization group showed obviously lessened liver fibrosis, significantly lowered expressions of NOX(4) and mesenchymal cell maker proteins, and enhanced expressions of epithelial cell marker proteins. CONCLUSION: Bile duct ligation up regulates mesenchymal phenotype-related proteins and NOX(4) protein expression and down-regulates the expression of epithelial phenotype-related proteins, and these changes can be reversed by subsequent bile duct recanalization. PMID- 26547342 TI - [Inhibitory effect of miR-20b on airway inflammation in asthmatic mice]. AB - OBJECTIVE: To explore the effect of miR-20b in inhibiting airway inflammation in a mouse model of asthma. METHODS: Female BALB/c mouse models of asthma, established by sensitizing and challenging the mice with a mixture of ovalbumin and aluminum hydroxide, were subjected to intranasal instillation of 20 ug miR 20b mimics or a miR-20b scramble every 3 days. On day 49, bronchoalveolar lavage fluid (BALF) was collected from the mice to examine the counts of total cells and different cell populations; HE staining was used to observe the pathological changes of the lung tissue, and the concentration of vascular endothelial growth factor (VEGF) in BALF was detected by ELISA. RESULTS: Treatment of the asthmatic mice with miR-20b mimics decreased not only the counts of the total leukocytes, neutrophils and eosinophils in the BALF but also mucus secretion in the airway and inflammatory cell infiltration around the bronchus, and lessened thickening of the airway mucosa. Instillation with miR-20b mimics significantly reduced the concentration of VEGF in BALF from 28.55+/-3.42 pg/mL in the asthma model group to 18.19+/-3.67 pg/mL (P<0.01). CONCLUSION: MiR-20b can inhibit airway inflammation in asthmatic mice possibly by reducing the expression of VEGF. PMID- 26547343 TI - [Longitudinal evaluation of reparative cartilage after matrix-associated autologous chondrocyte implantation with delayed gadolinium-enhanced MRI of the cartilage]. AB - OBJECTIVE: To estimate zonal variation of GAG content in reparative cartilage after matrix associated autologous chondrocyte implantation (MACI) using delayed gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC). METHODS: Seven patients (14 cartilage defects) undergoing MACI were recruited for examination with dGEMRIC at 3, 6, and 12 months after the procedure to calculate global and zonal longitudinal relaxivity (Delta R1) of the normal cartilage and reparative cartilage. RESULTS: The mean Delta R1 values of normal cartilage were significantly lower than those of reparative cartilage after MACI. A significant decrease was noted in the mean Delta R1 values from the deep layer to the superficial layer in the reparative cartilage at the 3 examinations. The Delta R1 values of the reparative cartilage showed no significant variation between 3 months and 6 months, but a significant decrease in the Delta R1 values occurred at 12 months. CONCLUSIONS: dGEMRIC is feasible to assess cartilage repair noninvasively following MACI. PMID- 26547344 TI - [Pretreatment with dexmedetomidine ameliorates renal inflammation and oxidative stress in rats with lipopolysaccharide-induced sepsis and acute kidney injury]. AB - OBJECTIVE: To investigate the effects of dexmedetomidine on inflammatory reaction, oxidative stress, and renal pathologies in a rat model of lipopolysaccharide (LPS)-induced sepsis. METHODS: Thirty-two SD rats were randomly divided into 4 groups, including a sham-operated group, LPS group with LPS (5 mg/kg) injection via the caudal vein 30 min before the operation, dexmedetomidine (Dex) +LPS group with additional Dex (10 ug/kg) injection via the caudal vein 10 min before LPS injection, and yohimbine+DEX+LPS group with intraperitoneal yohimbine (1 mg/kg) injection 40 min before and Dex injection 10 min before LPS injection. The levels of IL-1beta, SOD and MDA in the plasma and renal tissues were determined, and the renal pathologies were examined. RESULTS: Compared with the sham-operated rats, the rats in LPS group showed significantly increased IL-1beta and MDA levels and lowered SOD activity in the plasma and renal tissues (P<0.05) with obvious renal pathologies. Dex pretreatment obviously lowered IL-1beta and MDA levels and enhanced SOD activity in the plasma and renal tissues in LPS-challenged rats (P<0.05), and significantly lessened LPS-induced renal pathologies. CONCLUSION: Dex can protect the rats against LPS-induced renal injury by alleviating the inflammatory reactions and cytokine oxidative stress, and this effect is mediated possibly by alpha2 receptors. PMID- 26547345 TI - [Effect of rapid eye movement sleep deprivation on anxiety behavior and hippocampus NO level: different responses of adolescent and adult C57BL/6J mice]. AB - OBJECTIVE: To explore the difference between adolescent and adult C57BL/6J mice in response to rapid eye movement sleep (REMS) deprivation in terms of anxiety behavior and hippocampal NO level. METHODS: Both adolescent and adult C57BL/6J mice were divided into normal control (NC) group, wide platform (WP) group, and 24-hour REMS deprivation group, each group consisting of 15 mice. REMS deprivation models were established using a small platform in water tank, and the elevated plus maze test was used to examine anxiety behavior of the mice. After behavioral tests, the mice were sacrificed to examine hippocampal NO levels using enzyme-linked immunosorbent assay, and hippocampal nNOS protein expression was detected with Western blotting. RESULTS: The adolescent C57BL/6J mice showed no obvious differences in anxiety behaviors between the 3 groups, but NO level and nNOS expression in the hippocampus was significantly higher in REMSD group than in NC and WP groups (P<0.01). The adult mice in REMSD group, compared with those in the other two groups, exhibited significantly increased total number of arm entry (P<0.01), lowered number of open arm entry and reduced open arm time (P<0.01), increased number of close arm entry and prolonged close arm time (P<0.01 or 0.05); no obvious differences in NO level or nNOS expression in the hippocampus were found in the 3 groups of adult mice. CONCLUSION: REMS deprivation produces different effects on anxiety-related behaviors between adolescent and adult mice possibly in relation to their different responses in terms of NO levels and nNOS expression in the hippocampus. PMID- 26547346 TI - [Effects of vacuum drainage combined with heparin irrigation for treatment of scald burns with seawater immersion in rabbits]. AB - OBJECTIVE: To investigate the effect of closed vacuum drainage combined with heparin irrigation in the treatment of scald burns with seawater immersion in rabbits. METHODS: Twenty New Zealand rabbits were subjected to deep partial thickness scald burns in 4 regions on the bilateral skin of the spine. The wounds were managed with common dressing (group A), common dressing after seawater immersion (group B), closed vacuum drainage after seawater immersion (group C), or closed vacuum drainage combined with heparin irrigation after seawater immersion (group D). Wound effusion and tissue necrosis were observed at 1, 3, 5 and 7 days after the burns. Tissue samples were collected from the wounds for HE staining and immunohistochemistry for VEGF and CD31, and the changes of capillary endothelial cells in the wound were observed using electron microscopy. The water content in the wound tissues was determined, and the wound healing rate was calculated after the injury. RESULTS: Sea water immersion of the wound results in earlier onset of edema and more extensive tissue necrosis in the scalded rabbits. The mean necrotic area in groups C and D was smaller than that in group B early after the burns, and vacuum drainage promoted necrotic tissue elimination and accelerated wound healing. Early after the burns, water content in the tissues increased with time in all the groups and reached the highest level at 3 days, and was significantly lower in groups C and D than in group B. Pathologically, vascular endothelial cell damage at the wound site was worsened after seawater immersion. In group D, the basement membrane damage was milder and the endothelial cell membrane remained intact at the wound site, where new blood vessels occurred at 3 days after the burns, a time earlier than that in the other 3 groups with also the highest vascular density. CONCLUSIONS: Closed vacuum drainage combined with heparin irrigation can relieve edema at the scald wound with seawater immersion, improve microcirculation, accelerate the removal of necrotic tissue, and promote the growth of new blood vessels. PMID- 26547347 TI - [Epidemiological survey of high-risk human papillomavirus among 2501 woman]. AB - OBJECTIVE: To survey the prevalence of high-risk human papillomavirus (HPV) in woman in Guangzhou during the period from 2013 to 2014. METHODS: A total of 2501 women in Guangzhou seeking medical attention in our hospital underwent high-risk HPV genotype screening of cervical specimens using real-time PCR. RESULTS: The prevalence of high-risk HPV infection among the women was 14.85% (146/983) in the year 2013, similar to the rate of 14.56% (221/1518) in 2014 (Chi(2)=0.041, P=0.839); no significant differences were found in the high-risk HPV infection rates between different age groups in either 2013 (Chi(2)=2.916, P=0.572) or 2014 (Chi(2)=6.494, P=0.165). The constituent ratio of the 13 types of high-risk HPV showed no significant difference between 2013 and 2014 (Chi(2)=11.872, P=0.452). The 13 HPV genotypes detected, listed in a descending order of the constituent ratios, included HPV-52, -16, -58, -56, -39, -51, -68, -59, -31, -35, -18, -33 and -45 in 2013, and were HPV-52, -16, -58, -68, -18, -51, -56, -39, -31, -33, 59, -35 and-45 in 2014. CONCLUSION: We report a high prevalence of high-risk HPV among women in Guangzhou, which suggests the necessity of screening for high-risk HPV-DNA among women at all ages for prevention and early detection of cervical cancer. PMID- 26547348 TI - [Effect of one lung ventilation preconditioning on oxygenation during pediatric video-assisted thoracoscopic surgery]. AB - OBJECTIVE: To observe the effect of one lung ventilation (OLV) preconditioning on perioperative oxygenation during pediatric video-assisted thoracoscopic surgeries (VATS). METHODS: A total of 171 children aged 5 days to 11 years underwent VATS for empyema dissection and abscess excisions (n=55), mediastinal tumor resection (n=34), repair of the diaphragmatic hernia or diaphragmatic plication (n=21), pulmonary lobectomy or biopsy (n=43), or esophageal disease (n=18). Of these patients, 127 were younger than 3 years of age. A 5-Fr pediatric endobronchial blocker was used for OLV with a delivered inspired oxygen fraction (FiO(2)) of 1.0. After lateral decubitus, a sequential protocol of a 5- to 8-min OLV preconditioning and a 5-min two lung ventilation (TLV) was performed followed by OLV again before incision for VATS. In cases of a SpO(2)<95% without malposition of the blocker during OLV, a 5 cm H(2)O positive end expiratory pressure was applied; TLV was maintained for a SpO(2)<90%. RESULTS: OLV provided good surgical conditions in 160 cases. Acceptable saturations were achieved in 166 cases during OLV. In 2 cases in empyema group and 3 in esophageal disease group, the ventilation protocol was converted to intermittent TLV during the operation due to hypoxemia. In esophageal disease group, the procedure and OLV duration, postoperative ventilation time and length of stay (LOS) were the longest among the groups, and the number of cases developing postoperative atelectasis was greater than that in diaphragmatic hernia and pulmonary disease groups. In empyema and esophageal disease groups, the oxygenation index (PaO(2)/FiO(2)) after total collapse of the lung in OLV and after extubation were lower than that in mediastinal tumor group (P<0.05 or 0.01). CONCLUSION: A OLV preconditioning can maintain an acceptable oxygenation during pediatric OLV. A longer procedure and OLV duration is associated with a prolonged postoperative length of ventilation and LOS. PMID- 26547349 TI - [Effects of dexmedetomidine on propofol dosage in target-controlled infusion and hemodynamics during laparoscopic surgery under general anesthesia]. AB - OBJECTIVE: To assess the effects of dexmedetomidine (Dex) on propofol dosage in target-controlled infusion (TCI) and hemodynamics in patients undergoing laparoscopic surgery under general anesthesia. METHODS: Sixty patients undergoing laparoscopic surgery under general anesthesia were randomly divided into control group (n=30) and the Dex group (n=30). The patients in Dex group received a loading dose of Dex (1 ug/kg, infused within 10 min) before the surgery followed by continuous infusion at the rate of 0.3 ug.kg(-1).h(-1) till the end of the surgery, and the control patients received saline infusion in the same manner. Heart rate, blood pressure, bispectral index (BIS), and propofol dose in TCI were recorded during induction and maintenance of anesthesia. The incidence of hypotension and bradycardia were observed during and after the surgery. RESULTS: No difference was found in the incidence of hypotension and bradycardia between the control group and Dex group (P>0.05), but heart rate and blood pressure were lower in Dex group during extubation (P<0.05). The dose of propofol in TCI was significantly less in Dex group than in the control group (P<0.05). CONCLUSION: Dex can reduce hemodynamic abnormalities caused by extubation and decrease the dosage of propofol in TCI, and may serve as an ideal adjuvant drug for general anesthesia. PMID- 26547350 TI - [Risk factors of obstructive sleep apnea hypopnea syndrome and sleep hypopnea in patients with growth hormone-secreting pituitary adenoma]. AB - OBJECTIVE: To investigate the risk factors contributing to the development of obstructive sleep apnea hypopnea syndrome (OSAHS) and sleep hypopnea (SH) in patients with growth hormone-secreting pituitary adenoma (GHPA). METHODS: A total of 85 patients with GHPA recruited strictly according to the inclusion and exclusion criteria underwent sleep monitoring overnight. Clinical manifestations, laboratory data and magnet resonance images were collected for analysis of the risk factors of GHPA and SH using binary logistic regression analysis. RESULTS: The prevalence rate of OSAHS was 62.4% (53/85), and that of SH was 75.3% (64/85) in the recruited patients with GHPA. Regression analysis showed that age (OR=1.107) and BMI (OR=1.166) were the risk factors for OSAHS, and BMI (OR=1.334) was the risk factor of SH. CONCLUSION: Ageing and an increased BMI are independent risk factors for OSAHS and SH in patients with GHPA. Preoperative sleep monitoring should be routinely conducted to ensure early diagnosis of OSAHS and SH, and patients with GHPA should be advised to control their body weight to lower the mortality associated with the respiratory system. PMID- 26547351 TI - [Bicyclol combined with ganciclovir for treatment of infantile cytomegalovirus hepatitis]. AB - OBJECTIVE: To evaluate the therapeutic effects of bicyclol combined with ganciclocir on infantile cytomegalovirus hepatitis. METHODS: Seventy infants with cytomegalovirus hepatitis were randomized into treatment group (n=35) and control group (n=35) for a 2-week-long treatment with ganciclocir (5 mg/kg) with and without oral bicyclol (3 mg/kg, twice daily), respectively. RESULTS: In both groups, significant changes occurred in the levels of alanine aminotransferase, alkaline phosphatase, serum total bilirubin, serum total bile acid, and glutamyl transpeptidase after the 2-week treatment (P<0.01); these parameters differed significantly between the two groups after the treatment (P<0.01). Compared with those in the control group, the infants in the treatment group showed significantly better responses to the treatment (P<0.05) with a significantly higher rate of serum anti CMV IgM negativity (P<0.05). CONCLUSIONS: Bicyclol combined with ganciclocir can reduce glutamic pyruvic transaminase, alkaline phosphatase and serum total bilirubin, and decrease bile acid levels to lessen liver cell damage and promote the recovery of liver cells. PMID- 26547352 TI - [Laparoscopic diagnosis and treatment of rectum telangiectasia: report of a rare form of lower gastrointestinal hemorrhage]. AB - OBJECTIVE: We report a case of rectum telangiectasia, a rare form of lower gastrointestinal hemorrhage caused by vascular malformation. The patient underwent laparoscopic assisted abdomino-perineal resection of the sigmoid colon rectum telangiectasia. The extent and degree of pathological changes were observed directly from the intestinal wall during laparoscopic surgery, and after collection of biopsy evidence, concomitant definitive surgery was performed to achieve a minimally invasive effect. PMID- 26547353 TI - [Nucleolin expression is correlated with carcinogenesis and progression of cervical squamous cell carcinoma]. AB - OBJECTIVE: To investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma. METHODS: Fifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed. RESULTS: The specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6+/-0.3, 6.1+/-0.2, and 3.0+/-0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01). CONCLUSIONS: Overexpression of nucleolin plays an important role during carcinogenesis of cervical squamous cell carcinoma and is positively correlated with tumor progression of CIN and cervical squamous cell carcinoma. PMID- 26547354 TI - [Intensive hemoperfusion and long-term hemofiltration for treatment of paraquat poisoning: a case report]. AB - OBJECTIVE: A 20-year-old male patient was admitted in our department 14 h after paraquat poisoning at the dose of about 50 mL. The patient underwent intensive hemoperfusion for 2 h (3 times a day) for 9 consecutive days and received continuous renal replacement therapy (CRRT) in the mode of continuous veno-venous hemofiltration (CVVH) for 10 consecutive days in addition to routine medications. The biochemical indexes were monitored during the therapy. After the treatment, paraquat concentrations in the blood and urine were decreased, and the patient's urine volume (UV) increased, serum creatinine (Cr) level decreased, and the oxygenation index became normal. Dynamic CT scan showed no obvious pulmonary fibrosis. The patient was followed up for 6 months after discharge and no complaint of discomforts was reported. This case suggests that early intensive hemoperfusion and long-term CVVH may help improve the prognosis after paraquat poisoning. PMID- 26547355 TI - Impaired post-tetanic potentiation of muscle twitch in myasthenia gravis. AB - OBJECTIVE: The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG). METHODS: Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects. RESULTS: Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation contraction coupling in MG. CONCLUSIONS: Post-tetanic potentiation of muscle twitch is significantly diminished in MG, suggesting impaired excitation contraction coupling. SIGNIFICANCE: Measurement of post-tetanic potentiation using an accelerometer is a simple and sensitive method to detect impairment of excitation-contraction coupling in MG. PMID- 26547356 TI - Impaired interhemispheric processing in early Huntington's Disease: A transcranial magnetic stimulation study. PMID- 26547358 TI - Exfoliative erythroderma as a clinical manifestation of autoimmune bullous diseases. PMID- 26547359 TI - Reprint of "Cancer of the cervix: A sexually transmitted infection?". AB - When mortality patterns for cancer of the uterine cervix were compared with trends in incidence of sexually transmitted diseases in both England and Wales and in Scotland, there were striking associations between the temporal, social class, occupational, and geographic distributions of these diseases. The data suggest that exposure to sexually transmitted infection is an important determinant of cervical cancer. Although they are still young, women born after 1940 are already experiencing increased cervical-cancer mortality. If cervical cancer prevention and therapy remain unchanged, this generation's high risk of death from cervical cancer will probably continue to operate throughout their lives. PMID- 26547361 TI - Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction. AB - BACKGROUND: Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. METHODS: Sixty six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 * 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. KEY RESULTS: In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. CONCLUSIONS & INFERENCES: The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction. PMID- 26547360 TI - The what, when, and why of implementation frameworks for evidence-based practices in child welfare and child mental health service systems. AB - It is widely recognized that children in the child welfare system are particularly vulnerable to the adverse health and mental effects associated with exposure to abuse and neglect, making it imperative to have broad-based availability of evidence-based practices (EBPs) that can prevent child maltreatment and reduce the negative mental health outcomes for youth who are victims. A variety of EBPs exist for reducing child maltreatment risk and addressing the associated negative mental health outcomes, but the reach of these practices is limited. An emerging literature documents factors that can enhance or inhibit the success of EBP implementation in community service agencies, including how the selection of a theory-driven conceptual framework, or model, might facilitate implementation planning by providing guidance for best practices during implementation phases. However, limited research is available to guide decision makers in the selection of implementation frameworks that can boost implementation success for EBPs that focus on preventing child welfare recidivism and serving the mental health needs of maltreated youth. The aims of this conceptual paper are to (1) provide an overview of existing implementation frameworks, beginning with a discussion of definitional issues and the selection criteria for frameworks included in the review; and (2) offer recommendations for practice and policy as applicable for professionals and systems serving victims of child maltreatment and their families. PMID- 26547362 TI - Geostatistical simulations for radon indoor with a nested model including the housing factor. AB - The radon prone areas definition is matter of many researches in radioecology, since radon is considered a leading cause of lung tumours, therefore the authorities ask for support to develop an appropriate sanitary prevention strategy. In this paper, we use geostatistical tools to elaborate a definition accounting for some of the available information about the dwellings. Co-kriging is the proper interpolator used in geostatistics to refine the predictions by using external covariates. In advance, co-kriging is not guaranteed to improve significantly the results obtained by applying the common lognormal kriging. Here, instead, such multivariate approach leads to reduce the cross-validation residual variance to an extent which is deemed as satisfying. Furthermore, with the application of Monte Carlo simulations, the paradigm provides a more conservative radon prone areas definition than the one previously made by lognormal kriging. PMID- 26547363 TI - Nationwide expansion of a financial incentive program on fruit and vegetable purchases among Supplemental Nutrition Assistance Program participants: A cost effectiveness analysis. AB - High prices remain a formidable barrier for many people, especially those of low socioeconomic status, to adopt a healthier diet. The Food, Conservation, and Energy Act of 2008 mandated the U.S. Department of Agriculture (USDA) to conduct a pilot study to assess the impact of making fruits and vegetables more affordable for households in the Supplemental Nutrition Assistance Program (SNAP). Based on the USDA final report of the Healthy Incentives Pilot (HIP), a large-scale randomized trial in 2011-2012 that provided 30% rebate on targeted fruits and vegetables to 7500 study participants enrolled in the SNAP, we constructed a decision model to evaluate the cost-effectiveness of an expansion of the HIP to all SNAP households nationwide. The estimated life-time per capita costs of the HIP to the Federal government is $1323 in 2012 U.S. dollars, and the average gains in quality-adjusted life expectancy to a SNAP participant is 0.082 quality-adjusted life year (QALY), resulting in an incremental cost-effectiveness ratio (ICER) of $16,172 per QALY gained. Sensitivity analysis using Monte Carlo simulations indicates a 94.4% and 99.6% probability that the estimated ICER would be lower than the cost-effective threshold of $50,000 and $100,000 per QALY gained, respectively. Moreover, the estimated ICER of the HIP expansion tends to be competitive in comparison to other interventions that aimed at promoting fruit/vegetable intake among adult population. Findings from this study suggest that a nationwide expansion of the HIP is likely to nudge SNAP households towards purchasing and consuming more targeted fruits and vegetables. However, diet behavior modification is proportional to price change. When people's actual eating behaviors and what dietary guidelines recommend differ by several folds, even a 30% rebate closes just a small fraction of that gap and has limited beneficial impact on participants' weight management, disease prevention, and health-related quality of life. PMID- 26547364 TI - To clear or to fear: An innate perspective on factor VIII immunity. AB - The enigma that is factor VIII immunogenicity remains ever pertinent in the treatment of hemophilia A. Development of neutralizing antibodies against the therapeutic protein in 25-30% of patients likely depends on the appropriate activation of the innate immune response shortly following antigen encounter. Our understanding of this important immunological synapse remains ill-defined. In this review, we examine the three distinct factors contributing to the fate of factor VIII almost immediately after infusion: the characteristics of the protein, the cell, and the microenvironment. We propose a continuum between clearance and antigen presentation that facilitates removal of FVIII from circulation leading to either tolerance or immunity. PMID- 26547365 TI - iWAS--A novel approach to analyzing Next Generation Sequence data for immunology. AB - In this communication we describe a novel way to use Next Generation Sequence from the receptors expressed on T and B cells. This informatics methodology is named iWAS, for immunonome Wide Association Study, where we use the immune receptor sequences derived from T and B cells and the features of those receptors (sequences themselves, V/J gene usage, length and character each of the CDR3 sub regions) to define biomarkers of health and disease, as well as responses to therapies. Unlike GWAS, which do not provide immediate access to mechanism, the associations with immune receptors immediately suggest possible and plausible entree's into disease pathogenesis and treatment. PMID- 26547366 TI - Aberrant metastatic behavior and particular features of early gastric cancer. AB - In this paper, we have focused on the metastatic behavior of EGC and its particularities. The main factors that are currently considered as predictors of the metastatic behavior and that are used in the therapeutic decision (endoscopic resection vs surgical removal) are the tumor size (upper or bellow 2 cm), depth of infiltration, angiolymphatic invasion, the presence or absence of ulceration, and histologic type (undifferentiated vs differentiated carcinomas). However, most of the metastatic cases were published as case reports or case series. This is the reason why a proper estimation of metastatic risk in EGC is not well known. To date, 79 cases presenting bone metastases, three reports of brain metastases, and one EGC that was associated with skin metastasis were published. However, occult metastasis, lymph node micrometastasis, and skip metastasis can also occur and should be identified. Making a synthesis of the literature data that is correlated with our experience, we finally proposed the inclusion of the six Japanese subgrouping system, tumor size, angiolymphatic invasion, and micrometastasis as components of the pTNM staging system, which should be particularly adapted for EGC. PMID- 26547367 TI - Increased binding of circulating systemic lupus erythematosus autoantibodies to recombinant interferon alpha 2b. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various types of immunological abnormalities including circulating and tissue-fixed autoantibodies reactive with autoantigens. The mechanism that can explain the production of these antibodies is unclear. Here we address the binding specificity of SLE autoantibodies with recombinant alpha interferon 2b (hrIFN alpha-2b), commercially available interferon (IFN alpha-2b), and the gene (cIFN alpha-2b) encoding this interferon. hrIFN alpha-2b showed higher binding with naturally occurring SLE autoantibodies as compared to IFN alpha-2b (p < 0.05) or cIFN alpha-2b gene (p < 0.001) as assessed by direct binding, inhibition ELISA, and quantitative precipitin titration. The relative affinity of SLE autoantibodies for hrIFN alpha-2b, IFN alpha-2b, and cIFN alpha 2b gene was in the order of 1.13 * 10(-7) , 1.38 * 10(-6) , and 1.22 * 10(-6) , respectively. hrIFN alpha-2b is shown to have unique epitopes that would explain the possible antigenic role of hrIFN alpha-2b in the generation of SLE autoantibodies. Anti-hrIFN alpha-2b antibodies have been shown to represent an alternative immunological probe for the estimation of interferon alpha 2b in the serum of SLE patients. PMID- 26547368 TI - Elevated serum levels of Interleukin-37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis. AB - Interleukin-37 (IL-37) is closely associated with several inflammatory diseases. However, the role of IL-37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL-37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme-linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde-modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL-37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL-17 and IL-23. In addition, serum IL-37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I-II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL-37 levels were increased in patients with RA and were positively associated with disease activity, IL-17/IL 23 and bone loss in RA, suggesting that IL-37 may play a critical role in the pathogenesis of RA. PMID- 26547369 TI - Portal and splanchnic hemodynamics after partial splenic embolization in cirrhotic patients with hypersplenism. AB - To assess the acute effects of partial splenic embolization (PSE) on portal and splanchnic hemodynamics in patients with cirrhosis. Ninety-five patients with hypersplenism were included in the study. Duplex examinations were performed before and 3 and 7 days after PSE. Portal and splanchnic hemodynamics including vessel cross-sectional area (CSA), mean flow velocities (cm/s), blood flows (mL/min), Doppler indices as portal congestion index (CI), liver vascular index, hepatic artery and superior mesenteric artery (SMA) pulsatility and resistive indices (PI and RI), were performed before and after PSE. In our study, 69 of 95 patients were males (72.6%) and 26 females (27.3%). Chronic hepatitis C virus infection was the main cause of cirrhosis (81.1%). PSE failed technically in six patients (6.3%). After PSE, both CSA and CI significantly decreased (p < 0.05 and <0.01). The portal vein velocity significantly increased (p < 0.01). The portal flow volume (892.4 +/- 151 mL/min) did not show significant changes. The hepatic artery RI and PI showed a steady increase that became significant 7 days post-PSE (p < 0.05). The RI and PI of SMA increased significantly after 7 days of PSE (p < 0.05). PSE has an immediate portal decompression effect in patients with portal hypertension without reduction in portal flow. This effect on portal pressure should be investigated in future studies as a potential tool for management of acute variceal bleeding when other medical procedures fail. PMID- 26547370 TI - Nuclear, cytoplasmic, and stromal expression of ZEB1 in squamous and small cell carcinoma of the esophagus. AB - Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcriptional factor known to repress E-cadherin promoter and thus induce EMT. Expression of ZEB-1 has in numerous cancers been associated with aggressive disease and poor clinical outcome. Our aim was to investigate the expression of ZEB1 in esophageal squamous and small-cell carcinomas. Immunohistochemical staining was performed on tissue sections obtained from 151 patients with esophageal squamous cell carcinoma (ESCC) and 25 patients with primary small-cell carcinoma of the esophagus (PSCCE). Semi-quantitative analysis, and thus statistical analysis, has been accomplished on the samples. Immunohistochemistry revealed ZEB1 expression in the cytoplasm (64.9% of cases), in nuclei (11.3% of cases) and in tumor stroma (80.1% of cases) of ESCC. In PSCCE only nuclear staining (88.0% of cases) was observed. Weak cytoplasmic expression of ZEB1 in ESCC was associated with longer survival. Immunohistochemical evaluation of ZEB1 cytoplasmic expression in ESCC may have clinical prognostic value, but further studies are needed to fully understand the function as well as potential clinical and therapeutic implications of ZEB1 expression in cancers. PMID- 26547371 TI - Nuclear and mitochondrial DNAs microsatellite instability and mitochondrial DNA copy number in adenocarcinoma and squamous cell carcinoma of lung: a pilot study. AB - Mitochondrial genetic changes are considered as a key molecular step of mutations in various cancers. To clarify the role of genetic instability in lung cancer, we analyzed clinicopathological characteristics and frequencies of nuclear and mitochondrial microsatellite instability (nMSI and mtMSI), and alteration of mitochondrial DNA copy number (mtCN) in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of lung. DNA was isolated from 48 patients with ADC and 42 with SCC. Markers for nMSI, BAT 25 and 26, and markers for mtMSI, (C)n and (CA)n in mitochondrial D-loop region, were utilized. The mtCN were measured by real-time polymerase chain reaction. The nMSI was found in two patients (4.2%) of ADC and 6 (14.3%) of SCC. The mtMSI was detected in 10 patients (20.8%) of ADC and 8 (19.0%) of SCC. Mean mtCN was 5.05 +/- 8.17 and 3.34 +/- 5.14 in ADC and SCC respectively. The mtCN was increased in 35 patients (72.9%) of ADC and 30 (71.4%) of SCC. The mtMSI more frequently appeared in more advanced pathologic T stage in ADC (p = 0.003). Alterations of mtCN and a high frequency of mtMSI in our patient samples indicate that mitochondrial DNA is a potential molecular marker in lung cancers (ADC and SCC) correlating with their histological classification. PMID- 26547372 TI - Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline. AB - In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin. PMID- 26547373 TI - Antimycobacterial action of a new glycolipid-peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica. AB - In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface-enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X-ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid-peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid-peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria. PMID- 26547374 TI - Biofilm formation of ica operon-positive Staphylococcus epidermidis from different sources. AB - Information on the prevalence of biofilm-related factors (PIA, Bhp, Aap, Embp) in Staphylococcus epidermidis of animal origin is scarce. In this study, 263 S. epidermidis isolates of diverse origin (animal, farmers, patients, and laboratory staff) were investigated for the presence of the ica operon (icaRADBC). The icaRADBC-positive isolates were further characterized by means of biofilm formation, presence of other biofilm-related genes, antimicrobial resistance, and population structure. Of all isolates, 28.5% (n = 75) were icaRADBC-positive, including 16.5% of animal origin, 29.1% farmer isolates, and 44.6% hospital associated isolates (including patients and laboratory staff isolates). Most icaRADBC-positive isolates carried embp (n = 73), aap (n = 57), bhp (n = 22), and IS256 (n = 29). Statistical differences were found between animal and patient isolates for the presence of icaRADBC, bhp, and aap. No statistically significant relation was found between the presence of one or more genes and the level of biofilm formation. Most icaRADBC-positive isolates belonged to the clonal complex 5 (formerly 2) and most sequence types corresponded to types previously observed in community and nosocomial S. epidermidis populations. Although the prevalence of S. epidermidis in the nasal cavity of bovines and poultry is low, some isolates belong to STs related to ica-positive clinical strains. PMID- 26547375 TI - Incorrect statistical data. PMID- 26547357 TI - Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. AB - IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic. INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point. RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively. CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625. PMID- 26547376 TI - Sexual health among female Aboriginal university students in the Maritime Provinces of Canada: risk behaviours and health services use. AB - Background Young Aboriginal Canadian people are at increased risk of negative sexual health outcomes, including sexually transmissible infections (STIs) and unplanned pregnancy. Associations between Aboriginal ethnicity and sexual risk behaviours and related health services use among sexually active female university students in eastern Canada were examined. METHODS: A secondary analysis of online survey data collected from sexually active female university students under age 30 years from eight post-secondary institutions in the Maritime Provinces of Canada was carried out (N=5010). Students were asked about their ethnic backgrounds, health services use and sexual health behaviours. Logistic regressions were used to compare Aboriginal students to Caucasian students regarding their sexual health behaviours and services use. RESULTS: In adjusted analyses, Aboriginal students were seen to be more likely to not have used a condom (OR 2.37; 95% CI 1.34-4.18) or any form of effective contraception (OR 3.05; 95% CI 1.75-5.31) at last intercourse. They also were more likely to report any lifetime testing for pregnancy (OR 5.81; 95% CI 3.07-10.99) and STIs (OR 2.95; 95% CI 1.11-7.82). Aboriginal students accessed university health services as often as their Caucasian counterparts. CONCLUSIONS: Aboriginal women attending university in the Maritime Provinces of Canada engage in greater sexual risk taking than Caucasian women and report more related testing. Health services providers working with university students should be aware of these lower rates of barrier protection and use of contraception among Aboriginal women, and use healthcare visits as opportunities to engage these women in reducing their sexual risk taking. PMID- 26547377 TI - Mixed lineage kinase 3 connects hepatocellular lipotoxicity with macrophage chemotaxis. PMID- 26547378 TI - Peak Vertical Force and Vertical Impulse in Dogs With Cranial Cruciate Ligament Rupture and Meniscal Injury. AB - OBJECTIVE: To compare the peak vertical force (PVF) and vertical impulse (VI) in dogs with naturally occurring cranial cruciate ligament (CCL) disease with or without concurrent meniscal injury. STUDY DESIGN: Prospective case series. STUDY POPULATION: Client-owned dogs with naturally occurring CCL disease. METHODS: Dogs with hind limb lameness because of CCL disease that required surgery underwent force plate gait analysis. Force plate analysis was performed at a walking gait (speed 1-1.3 m/s; acceleration +/- 0.5 m/s(2)) and data were analyzed using commercial proprietary software. Meniscal injury was diagnosed either by mini arthrotomy or arthroscopy. The primary outcome was PVF and the secondary outcome was VI. Comparisons were made between dogs with or without meniscal injury, and dogs with partial or complete CCL rupture. RESULTS: Forty dogs were included. Meniscal injury was present in 18/40 dogs (45%). PVF (P = .003) and VI (P = .01) were significantly lower in dogs with meniscal injury than in dogs without meniscal injury. CONCLUSION: Dogs with CCL disease and medial meniscal injury had significantly reduced PVF and VI. PMID- 26547379 TI - Iris pigmentation as a quantitative trait: variation in populations of European, East Asian and South Asian ancestry and association with candidate gene polymorphisms. AB - In this study, we present a new quantitative method to measure iris colour based on high-resolution photographs. We applied this method to analyse iris colour variation in a sample of individuals of East Asian, European and South Asian ancestry. We show that measuring iris colour using the coordinates of the CIELAB colour space uncovers a significant amount of variation that is not captured using conventional categorical classifications, such as 'brown', 'blue' or 'green'. We tested the association of a selected panel of polymorphisms with iris colour in each population group. Six markers showed significant associations with iris colour in the European sample, three in the South Asian sample and two in the East Asian sample. We also observed that the marker HERC2 rs12913832, which is the main determinant of 'blue' versus 'brown' iris colour in European populations, is also significantly associated with central heterochromia in the European sample. PMID- 26547380 TI - [Dosimetric comparaison between VMAT and tomotherapy with para-aortic irradiation for cervix carcinoma]. AB - PURPOSE: Intensity-modulated radiotherapy (IMRT) has proven its dosimetric superiority over conformational radiotherapy for cervix cancers in terms of digestive toxicity. Volumetric modulated arctherapy (VMAT) has shown its dosimetric interest when compared to IMRT with static beams. The purpose of our study was to compare conformational radiotherapy, VMAT and tomotherapy for cervical cancers with para-aortic lymph nodes irradiation. PATIENTS AND METHODS: The dosimetric data from ten patients were compared between the three techniques, with collection of the dose received by the planning target volume, kidneys, bowel, rectum, bladder, bone marrow and spinal cord, as well as the complete dose. RESULTS: There was a significant difference in favour of VMAT and tomotherapy when compared with conformational radiotherapy for the organs at risk: intestines (V(20 Gy), V(30 Gy) and V(45 Gy)), rectum (V(30 Gy) and V(45 Gy)), bladder (V(30 Gy) and V(45 Gy)) and kidneys (V(12 Gy), Daverage, V(20 Gy)). Volumes receiving 20, 30 and 45 Gy were significantly higher in conformational radiotherapy than in VMAT and tomotherapy. There was a significant difference in favour of tomotherapy when compared with VMAT for V(12 Gy) in kidneys and V(45 Gy) in the bladder. CONCLUSION: This study confirms the interest of VMAT and tomotherapy for pelvic and para-aortic lymph nodes irradiation of cervix cancer when compared with conformational radiotherapy. There was little difference between VMAT and tomotherapy, except for kidney sparing, which was better with tomotherapy and thus may be interesting for patients receiving nephrotoxic chemotherapy. PMID- 26547381 TI - Folylpolyglutamate synthetase splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and other chemotherapeutics and mediate chemoresistance. AB - Methotrexate (MTX), a folate antagonist which blocks de novo nucleotide biosynthesis and DNA replication, is an anchor drug in acute lymphoblastic leukemia (ALL) treatment. However, drug resistance is a primary hindrance to curative chemotherapy in leukemia and its molecular mechanisms remain poorly understood. We have recently shown that impaired folylpolyglutamate synthetase (FPGS) splicing possibly contributes to the loss of FPGS activity in MTX resistant leukemia cell line models and adult leukemia patients. However, no information is available on the possible splicing alterations in FPGS in pediatric ALL. Here, using a comprehensive PCR-based screen we discovered and characterized a spectrum of FPGS splicing alterations including exon skipping and intron retention, all of which proved to frequently emerge in both pediatric and adult leukemia patient specimens. Furthermore, an FPGS activity assay revealed that these splicing alterations resulted in loss of FPGS function. Strikingly, pulse-exposure of leukemia cells to antifolates and other chemotherapeutics markedly enhanced the prevalence of several FPGS splicing alterations in antifolate-resistant cells, but not in their parental antifolate-sensitive counterparts. These novel findings suggest that an assortment of deleterious FPGS splicing alterations may constitute a mechanism of antifolate resistance in childhood ALL. Our findings have important implications for the rational overcoming of drug resistance in individual leukemia patients. PMID- 26547382 TI - Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis? AB - PURPOSE: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. METHODS AND MATERIALS: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. chi(2) tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. RESULTS: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: chi(2) (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). CONCLUSION: Patients who were taking ACEIs were significantly less likely to have high-grade proctitis after radical radiation therapy with neoadjuvant or adjuvant hormone therapy (P<.001). The intake of ACEIs was significantly associated with a reduced risk of radiation-induced proctitis and also with acceleration of its resolution. PMID- 26547383 TI - Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study. AB - PURPOSE: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). METHODS AND MATERIALS: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. RESULTS: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. CONCLUSIONS: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT. PMID- 26547384 TI - Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis. AB - BACKGROUND: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. METHODS AND MATERIALS: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. RESULTS: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. CONCLUSION: This retrospective population based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease. PMID- 26547385 TI - Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study. AB - PURPOSE: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. METHODS AND MATERIALS: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming alpha/beta of 10 [EQD2]10 = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). RESULTS: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. CONCLUSIONS: Adaptive IGRT using plan-of-the day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation. PMID- 26547386 TI - Examination of Industry Payments to Radiation Oncologists in 2014 Using the Centers for Medicare and Medicaid Services Open Payments Database. AB - PURPOSE: To use the Centers for Medicare and Medicaid Services Open Payments database to characterize payments made to radiation oncologists and compare their payment profile with that of medical and surgical oncologists. METHODS AND MATERIALS: The June 2015 release of the Open Payments database was accessed, containing all payments made to physicians in 2014. The general payments dataset was used for analysis. Data on payments made to medical, surgical, and radiation oncologists was obtained and compared. Within radiation oncology, data regarding payment category, sponsorship, and geographic distribution were identified. Basic statistics including mean, median, range, and sum were calculated by provider and by transaction. RESULTS: Among the 3 oncologic specialties, radiation oncology had the smallest proportion (58%) of compensated physicians and the lowest mean ($1620) and median ($112) payment per provider. Surgical oncology had the highest proportion (84%) of compensated physicians, whereas medical oncology had the highest mean ($6371) and median ($448) payment per physician. Within radiation oncology, nonconsulting services accounted for the most money to physicians ($1,042,556), whereas the majority of the sponsors were medical device companies (52%). Radiation oncologists in the West accepted the most money ($2,041,603) of any US Census region. CONCLUSIONS: Radiation oncologists in 2014 received a large number of payments from industry, although less than their medical or surgical counterparts. As the Open Payments database continues to be improved, it remains to be seen whether this information will be used by patients to inform choice of providers or by lawmakers to enact policy regulating physician-industry relationships. PMID- 26547387 TI - No data, no problem, no action: parenting programs in low-income countries. Making the social-emotional outcomes more visible. AB - BACKGROUND: Parenting programs are delivered in many low income countries in an effort to address the effects of insufficient cognitive stimulation, major social emotional risk factors related to inadequate caregiver sensitivity and responsiveness, maternal depression, violence and biological risk factors. However, the outcomes of these programs are often untested because of methodological limitations in the existing evaluation tools available for cross cultural research, and especially those related to social-emotional development and functioning. METHOD: This study takes an approach that involves organizing data from focus groups collected following caregiver participation in a parenting program, Learning Through Play (LTP) delivered in 11 low income countries. The LTP program has as its aim to increase parent knowledge and influence parental practice regarding the essential components of early development of children aged birth to 6 years. The purpose of systematically organizing focus group data was to illustrate a means by which program developers worldwide can discuss outcomes of program participation, particularly in social-emotional domains that have been overlooked in past studies on parenting programs. RESULTS AND CONCLUSION: The findings from this study suggest that qualitative outcome data can be organized to make the social-emotional outcomes of participation in parenting programs more visible. PMID- 26547388 TI - QSAR Models Guided by Molecular Dynamics Applied to Human Glucokinase Activators. AB - In this study, quantitative structure-activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three dimensional box comprised of 2 A cells. The models were generated by the technique that combines genetic algorithms and partial least squares. The best alignment models generated with a determination coefficient (r(2)) between 0.674 and 0.743 and cross-validation (q(2)) between 0.509 and 0.610, indicating good predictive capacity. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators. PMID- 26547389 TI - Placental stem cells. AB - The placenta represents a reservoir of progenitor, stem cells and epithelial cells that have been shown to differentiate into various types, including adipogenic, osteogenic, myogenic, hepatogenic, cardiac, pancreatic, endothelial, pulmonary and neurogenic lineages. This review focuses on the properties of placenta-derived cells, and it evaluates their current therapeutic applications in regenerative medicine and cell transplantations. Ongoing clinical and preclinical studies are investigating the safety and efficacy of the human amniotic epithelial cells (hAECs), human amniotic mesenchymal stromal cells (hAMSCs) and chorionic mesenchymal stromal cells (hCMSCs). The establishment of biobanks for placental stem cells will enable the translation of scientific research into the clinic. The advantage of the placenta as a cellular source is that it contains different cell lineages, such as the haematopoietic lineage that originates from the chorion, allantois and yolk sac, and the mesenchymal lineage that originates from the chorion and amnion. In this review, we address advances in placental stem cell characterization, and we explore their possible uses in cell therapy. PMID- 26547390 TI - Areas V1 and V2 show microsaccade-related 3-4-Hz covariation in gamma power and frequency. AB - Neuronal gamma-band synchronization (25-80 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. However, recent studies in macaque visual cortex have used single-trial analyses to show that both power and frequency of gamma oscillations exhibit substantial moment-by-moment variation. This has raised the question of whether these apparently random variations might limit the functional role of gamma-band synchronization for neural processing. Here, we studied the moment-by-moment variation in gamma oscillation power and frequency, as well as inter-areal gamma synchronization, by simultaneously recording local field potentials in V1 and V2 of two macaque monkeys. We additionally analyzed electrocorticographic V1 data from a third monkey. Our analyses confirm that gamma-band synchronization is not stationary and sustained but undergoes moment by-moment variations in power and frequency. However, those variations are neither random and nor a possible obstacle to neural communication. Instead, the gamma power and frequency variations are highly structured, shared between areas and shaped by a microsaccade-related 3-4-Hz theta rhythm. Our findings provide experimental support for the suggestion that cross-frequency coupling might structure and facilitate the information flow between brain regions. PMID- 26547391 TI - Subrenal capsule grafting technology in human cancer modeling and translational cancer research. AB - Patient-derived xenograft (PDX) cancer models with high fidelity are in great demand. While the majority of PDXs are grafted under the skin of immunodeficient mice, the Living Tumor Laboratory (LTL), using unique subrenal capsule grafting techniques, has successfully established more than 200 transplantable PDX models of various low to high grade human cancers. The LTL PDX models retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, metastatic ability, and response to treatment. The PDXs are stored frozen at early transplant generations in a resurrectable form, which eliminates continuous passaging in mice, thus ensuring maintenance of the high biologic and molecular fidelity and reproducibility of the models. The PDX models have been demonstrated to be powerful tools for (i) studies of cancer progression, metastasis and drug resistance, (ii) evidenced-based precision cancer therapy, (iii) preclinical drug efficacy testing and discovery of new anti-cancer drug candidates. To better provide resources for the research community, an LTL website (www.livingtumorlab.com) has been designed as a publicly accessible database which allows researchers to identify PDX models suitable for translational/preclinical cancer research. In summary, subrenal capsule grafting technology maximizes both tumor engraftment rate and retention of human cancer heterogeneity. Moreover, the method makes possible the recovery of PDXs from frozen stocks for further applications, thus providing a powerful platform for translational cancer research. PMID- 26547392 TI - Effectiveness of Jigsaw learning compared to lecture-based learning in dental education. AB - AIM: The objective of this study was to evaluate the success levels of students using the Jigsaw learning method in dental education. METHOD: Fifty students with similar grade point average (GPA) scores were selected and randomly assigned into one of two groups (n = 25). A pretest concerning 'adhesion and bonding agents in dentistry' was administered to all students before classes. The Jigsaw learning method was applied to the experimental group for 3 weeks. At the same time, the control group was taking classes using the lecture-based learning method. At the end of the 3 weeks, all students were retested (post-test) on the subject. A retention test was administered 3 weeks after the post-test. Mean scores were calculated for each test for the experimental and control groups, and the data obtained were analysed using the independent samples t-test. RESULTS: No significant difference was determined between the Jigsaw and lecture-based methods at pretest or post-test. The highest mean test score was observed in the post-test with the Jigsaw method. In the retention test, success with the Jigsaw method was significantly higher than that with the lecture-based method. CONCLUSION: The Jigsaw method is as effective as the lecture-based method. PMID- 26547393 TI - Xenogeneic collagen matrix for periodontal plastic surgery procedures: a systematic review and meta-analysis. AB - Several clinical trials describe the effectiveness of xenogeneic collagen matrix (XCM) as an alternative option to surgical mucogingival procedures for the treatment of marginal tissue recession and augmentation of insufficient zones of keratinized tissue (KT). The aim of this systematic review and meta-analysis was to evaluate the clinical and patient-centred outcomes of XCM compared to other mucogingival procedures. Applying guidelines of the Preferred Reporting Items for Systematic Reviews and Meta analyses statement, randomized controlled trials were searched for in electronic databases and complemented by hand searching. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool and data were analysed using statistical software. A total of 645 studies were identified, of which, six trials were included with 487 mucogingival defects in 170 participants. Overall meta-analysis showed that connective tissue graft (CTG) in conjunction with the coronally advanced flap (CAF) had a significantly higher percentage of complete/mean root coverage and mean recession reduction than XCM. Insufficient evidence was found to determine any significant differences in width of KT between XCM and CTG. The XCM had a significantly higher mean root coverage, recession reduction and gain in KT compared to CAF alone. No significant differences in patient's aesthetic satisfaction were found between XCM and CTG, except for postoperative morbidity in favour of XCM. Operating time was significantly reduced with the use of XCM compared with CTG but not with CAF alone. There is no evidence to demonstrate the effectiveness of XCM in achieving greater root coverage, recession reduction and gain in KT compared to CTG plus CAF. Superior short-term results in treating root coverage compared with CAF alone are possible. There is limited evidence that XCM may improve aesthetic satisfaction, reduce postoperative morbidity and shorten the operating time. Further long-term randomized controlled trials are required to endorse the supposed advantages of XCM. PMID- 26547395 TI - Reduced Circulating Concentration of Brain-derived Neurotrophic Factor is Associated with Peri- and Post-implantation Failure following In Vitro Fertilization-Embryo Transfer. AB - PROBLEM: We evaluated associations between brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) and pregnancy outcome in women undergoing in vitro fertilization-embryo transfer (IVF-ET). METHOD OF STUDY: Sera obtained on days 24 and 28 of an IVF cycle from women with a live birth, spontaneous abortion, biochemical pregnancy, not pregnant, or an ectopic pregnancy were retrospectively analyzed for BDNF and NT4 by ELISA. RESULTS: Median BDNF levels were higher in women with a live birth compared to women with an ectopic pregnancy (P < 0.0001), spontaneous abortion (P < 0.0001), or a biochemical pregnancy (P = 0.0004), but not in women who did not become pregnant. NT4 was detected in <25% of sera and did not differ by outcome. There was no association between BDNF level and oocyte or pre-transfer embryo parameters. CONCLUSION: Decreased circulating BDNF early in an IVF cycle is associated with adverse peri- and/or post-implantation events and subsequent pregnancy failure. PMID- 26547394 TI - Secondary contact and local adaptation contribute to genome-wide patterns of clinal variation in Drosophila melanogaster. AB - Populations arrayed along broad latitudinal gradients often show patterns of clinal variation in phenotype and genotype. Such population differentiation can be generated and maintained by both historical demographic events and local adaptation. These evolutionary forces are not mutually exclusive and can in some cases produce nearly identical patterns of genetic differentiation among populations. Here, we investigate the evolutionary forces that generated and maintain clinal variation genome-wide among populations of Drosophila melanogaster sampled in North America and Australia. We contrast patterns of clinal variation in these continents with patterns of differentiation among ancestral European and African populations. Using established and novel methods we derive here, we show that recently derived North America and Australia populations were likely founded by both European and African lineages and that this hybridization event likely contributed to genome-wide patterns of parallel clinal variation between continents. The pervasive effects of admixture mean that differentiation at only several hundred loci can be attributed to the operation of spatially varying selection using an FST outlier approach. Our results provide novel insight into the well-studied system of clinal differentiation in D. melanogaster and provide a context for future studies seeking to identify loci contributing to local adaptation in a wide variety of organisms, including other invasive species as well as temperate endemics. PMID- 26547397 TI - Biologically derived fertilizer: A multifaceted bio-tool in methane mitigation. AB - Methane emissions are affected by agricultural practices. Agriculture has increased in scale and intensity because of greater food, feed and energy demands. The application of chemical fertilizers in agriculture, particularly in paddy fields, has contributed to increased atmospheric methane emissions. Using organic fertilizers may improve crop yields and the methane sink potential within agricultural systems, which may be further improved when combined with beneficial microbes (i.e. biofertilizers) that improve the activity of methane oxidizing bacteria such as methanotrophs. Biofertilizers may be an effective tool for agriculture that is environmentally beneficial compared to conventional inorganic fertilizers. This review highlights and discusses the interplay between ammonia and methane oxidizing bacteria, the potential interactions of microbial communities with microbially-enriched organic amendments and the possible role of these biofertilizers in augmenting the methane sink potential of soils. It is suggested that biofertilizer applications should not only be investigated in terms of sustainable agriculture productivity and environmental management, but also in terms of their effects on methanogen and methanotroph populations. PMID- 26547398 TI - Toxicological effects of bisphenol A on growth and antioxidant defense system in Oryza sativa as revealed by ultrastructure analysis. AB - The present study was conducted to evaluate the effect of bisphenol A (BPA) on rice seedlings grown in a hydroponic system. The obtained results demonstrated that at lower concentration (up to 10uM) BPA had some stimulatory effects on the growth of rice seedlings but at higher doses it significantly inhibited seedlings growth. The photosynthetic pigments were significantly decreased by high doses of BPA. Exposure to BPA caused increased membrane permeability in root cells and resulted in increased concentration of reactive oxygen species (ROS) and increased lipid peroxidation as revealed by thiobarbituric acid reactive substances (TBARS) assay. In leaves, superoxide dismutase (SOD) activity exhibited an increase at lower concentrations of BPA but was inhibited at the highest dose (200uM) of BPA. At 100uM of BPA, a significant increase in antioxidant activities in leaves was observed but at 200uM this activity was inhibited. In roots, a significant decrease in enzymes activity was recorded at the highest concentration of BPA (200uM); however, ascorbate peroxidase (APX) and catalase (CAT) activities were significantly increased at the concentrations of 10 and 50uM in comparison to the control. Moreover, the present results revealed that BPA severely affected cell organelles in rice seedlings. It can be concluded that the observed adverse effects in rice seedlings by BPA in the present study could be attributed to the oxidative stress caused by BPA. PMID- 26547399 TI - Effects of Placental Transfusion on Neonatal and 18 Month Outcomes in Preterm Infants: A Randomized Controlled Trial. AB - OBJECTIVE: To assess the effect of delayed cord clamping (DCC) vs immediate cord clamping (ICC) on intraventricular hemorrhage (IVH), late onset sepsis (LOS), and 18-month motor outcomes in preterm infants. STUDY DESIGN: Women (n = 208) in labor with singleton fetuses (<32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (<10 seconds). The primary outcomes were IVH, LOS, and motor outcomes at 18-22 months corrected age. Intention-to-treat was used for primary analyses. RESULTS: Cord clamping time was 32 +/- 16 (DCC) vs 6.6 +/- 6 (ICC) seconds. Infants in the DCC and ICC groups weighed 1203 +/- 352 and 1136 +/ 350 g and mean gestational age was 28.3 +/- 2 and 28.4 +/- 2 weeks, respectively. There were no differences in rates of IVH or LOS between groups. At 18-22 months, DCC was protective against motor scores below 85 on the Bayley Scales of Infant Development, Third Edition (OR 0.32, 95% CI 0.10-0.90, P = .03). There were more women with preeclampsia in the ICC group (37% vs 22%, P = .02) and more women in the DCC group with premature rupture of membranes/preterm labor (54% vs 75%, P = .002). Preeclampsia halved the risk of IVH (OR 0.50, 95% CI 0.2 1.0) and premature rupture of membranes/preterm labor doubled the risk of IVH (OR 2.0, 95% CI 1.2-4.3). CONCLUSIONS: Although DCC did not alter the incidence of IVH or LOS in preterm infants, it improved motor function at 18-22 months corrected age. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00818220 and NCT01426698. PMID- 26547400 TI - Complementary Serologic Investigations in Children with Celiac Disease Is Unnecessary during Follow-Up. AB - OBJECTIVES: To determine the frequency of nutritional deficiencies and thyroid dysfunction in children with celiac disease (CD) and during follow-up after initiation of a gluten-free diet. Laboratory investigations of hemoglobin, ferritin, calcium, folate, vitamin B12, vitamin D, and thyroid function are regularly ordered in children with CD despite sufficient evidence for these. STUDY DESIGN: Between 2009 and 2014, test results of hemoglobin, ferritin, folate, vitamin B12, calcium, vitamin D (25[OH]D), free thyroxin, and thyroid stimulating hormone of children with CD regularly seen at the Leiden University Medical Center were investigated. Laboratory reference ranges were used to define abnormal results. Pearson chi(2) test for trend, unpaired t test, and 1-way ANOVA were used for statistical analysis. RESULTS: Of the 182 children evaluated, 119 were newly diagnosed. On average, 17% of results per year were missing because of incomplete blood investigations. Iron deficiency (28%) and iron deficiency anemia (9%) were found at the time of diagnosis of CD. Folate (14%), vitamin B12 (1%), and vitamin D deficiencies (27%) were also seen. No hypocalcemia or thyroid dysfunction was found. At follow-up, iron deficiency, iron deficiency anemia, and folate and vitamin D deficiency were observed in 8%, 2%, 3%, and 25% of patients, respectively. Vitamin B12 deficiency, hypocalcemia, and thyroid disease were not found. CONCLUSIONS: Complementary blood investigations are relevant at the time of diagnosis of CD but have little diagnostic yield during follow-up visits once the patient is placed on a gluten-free diet. Thus, we recommend that these variables only be assessed on indication, such as fatigue or abnormal growth. PMID- 26547401 TI - Practice Patterns and Adverse Events of Nitrous Oxide Sedation and Analgesia: A Report from the Pediatric Sedation Research Consortium. AB - OBJECTIVES: To describe practice patterns and adverse events associated with nitrous oxide (N2O) administration as the primary sedative outside the operating room in varied settings by a diverse range of providers, and to identify patient and sedation characteristics associated with adverse events. STUDY DESIGN: Data prospectively collected by the Pediatric Sedation Research Consortium, which is comprised of 40 children's and general/community hospitals, was retrospectively analyzed for children who received N2O as the primary sedative. Descriptive measures of patient and sedation characteristics and adverse events were reported. A multivariable regression model was used to assess potential associations between patient and sedation characteristics and adverse events. RESULTS: A total of 1634 N2O administrations were identified. The majority was performed in sedation units, and most by advanced practice nurses or physician assistants. The most common adjunct medication was midazolam. There was a low prevalence of adverse events (6.5%), with vomiting as the most common (2.4%) and only 3 (0.2%) serious adverse events reported. The odds of vomiting increased when concomitant opioids were administered (OR 2.89, 95% CI 1.14, 7.32) and when nil per os (NPO) clear fluids <2 hours (OR 4.16, 95% CI 1.61, 10.76). NPO full meal <6 hours did not change the odds of vomiting (OR 1.42, 95% CI 0.57, 3.57). There were no aspiration events. CONCLUSIONS: There was a very low prevalence of serious adverse events during N2O administration in children outside of the operating room and by nonanesthesiologists. The odds of vomiting increased when concomitant opioids were administered and NPO clear fluids <2 hours. PMID- 26547402 TI - Hospital Costs for Neonates and Children Supported with Extracorporeal Membrane Oxygenation. AB - OBJECTIVE: To assess the characteristics associated with high hospital cost for patients receiving extracorporeal membrane oxygenation (ECMO) to identify a cohort of high-resource users. STUDY DESIGN: Cost for hospitalization, during which ECMO support was used, was calculated from hospital charges reported in the 2012 Health Care Cost and Use Project Kid's Inpatient Database. Patients were categorized into 6 diagnostic groups: (1) cardiac surgery; (2) nonsurgical heart disease; (3) congenital diaphragmatic hernia; (4) neonatal respiratory failure; (5) pediatric respiratory failure; and (6) sepsis. We categorized cost into 4 groups based on quartiles. We compared ECMO cost with hospital cost for bone marrow, liver, and kidney transplants performed during the same year. RESULTS: Median hospital cost for children supported with ECMO (n = 1465) was $230,425 (IQR: $126,599-$420,960). In a multivariable model, lower cost was associated with neonatal respiratory failure (OR: 0.19) and sepsis (OR 0.53) compared with cardiac surgery (OR: 1.88), whereas greater cost was associated with smaller hospital bed-size <99 (OR: 3.49) and 100-399 beds (OR: 3.03) compared with hospitals >400 beds, hospital location (Midwest [OR: 1.74] and West [OR 2.18] compared with North-East), and complications such as renal failure (OR: 3.77) and thromboembolic complications (OR 1.60). Hospital cost per survivor was greater for ECMO ($519,450) than bone marrow transplantation ($207,212), liver ($231,755), or kidney transplantation ($82,008) groups. CONCLUSIONS: Hospitalization cost for children supported with ECMO is high. Diagnosis, hospital characteristics, and presence of complications are associated with increased cost. PMID- 26547404 TI - Decline in Forced Expiratory Volume in 1 Second in Cystic Fibrosis--Watch the Pendulum Swing. PMID- 26547403 TI - Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas. PMID- 26547405 TI - [Guillain-Barre syndrome in infancy: The importance of electroneuromyography]. AB - Guillain-Barre Syndrome (GBS) is rare in infancy, and the diagnosis of atypical forms is difficult in this age range. The main differential diagnoses include congenital neuropathy. Biological and electrophysiological investigations remain important to confirm diagnosis and start treatment quickly. We report the case of an 8-month-old boy who presented with acquired hypotonia due to progressive descending limb paralysis, predominant in the upper limbs, associated with unexplained severe neutropenia. GBS was diagnosed thanks to the association of albuminocytologic dissociation on cerebrospinal fluid and demyelinating sensomotor polyradiculoneuropathy on electroneuromyography. Only one cycle of treatment with intravenous immunoglobulins was sufficient to achieve complete recovery after 1 year. Physicians should know that atypical forms of GBS exist in infants, in order to recognize the syndrome, rule out differential diagnoses, and start treatment as soon as possible. Medical follow-up remains important before and after remission, especially in infants, to identify relapses, which might be the symptom of a genetic neuropathy or a chronic inflammatory disease. PMID- 26547406 TI - Enhancing surgical safety using digital multimedia technology. AB - BACKGROUND: The purpose of this study was to examine whether incorporating digital and video multimedia components improved surgical time-out performance of a surgical safety checklist. METHODS: A prospective pilot study was designed for implementation of a multimedia time-out, including a patient video. Perceptions of the staff participants were surveyed before and after intervention (Likert scale: 1, strongly disagree to 5, strongly agree). RESULTS: Employee satisfaction was high for both time-out procedures. However, employees appreciated improved clarity of patient identification (P < .05) and operative laterality (P < .05) with the digital method. About 87% of the respondents preferred the digital version to the standard time-out (75% anesthesia, 89% surgeons, 93% nursing). Although the duration of time-outs increased (49 and 79 seconds for standard and digital time-outs, respectively, P > .001), there was significant improvement in performance of key safety elements. CONCLUSION: The multimedia time-out allows improved participation by the surgical team and is preferred to a standard time out process. PMID- 26547407 TI - Synthesis, quorum sensing inhibition and docking studies of 1,5-dihydropyrrol-2 ones. AB - Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli use N acylated l-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a chief regulatory and cell-to-cell communication system. QS is responsible for social adaptation, virulence factor production, biofilm production and antibiotic resistance in bacteria. Fimbrolides, a class of halogenated furanones isolated from the red marine alga Delisea pulchra, have been shown to exhibit promising QS inhibitory activity against various Gram-negative and Gram-positive bacterial strains. In this work, various lactam analogues of fimbrolides viz., 1,5-dihydropyrrol-2-ones, were designed and synthesized via an efficient lactamization protocol. All the synthesized analogues were tested for QS inhibition against the E. coli AHL-monitor strain JB357 gfp (ASV). Compound 17a emerged as the most potent compound, followed by 9c, with AIC40 values (the ratio of synthetic inhibitor to natural AHL signaling molecule that is required to lower GFP expression to 40%) of 1.95 and 19.00, respectively. Finally, the potential binding interactions between the synthesized molecules and the LasR QS receptor were studied by molecular docking. Our results indicate that 1,5 dihydropyrrol-2-ones have the ability to serve as potential leads for the further development of novel QS inhibitors as antimicrobial therapeutics. PMID- 26547408 TI - Smoking cessation and the incidence of pre-diabetes and type 2 diabetes: a cohort study. AB - AIMS: Smoking cessation has been suggested to increase the short-term risk of type 2 diabetes mellitus (T2DM). This study aimed at assessing the association between smoking cessation and incidence of T2DM and impaired fasting glucose (IFG). METHODS: Data from participants in the CoLaus study, Switzerland, aged 35 75 at baseline and followed for 5.5years were used. Participants were classified as smokers, recent (<=5years), long-term (>5years) quitters, and non-smokers at baseline. Outcomes were IFG (fasting serum glucose (FSG) 5.6-6.99mmol/l) and T2DM (FSG >=7.0mmol/l and/or treatment) at follow up. RESULTS: 3,166 participants (63% women) had normal baseline FSG, of whom 26.7% were smokers, 6.5% recent quitters, and 23.5% long-term quitters. During follow-up 1,311 participants (41.4%) developed IFG (33.6% women, 54.7% men) and 47 (1.5%) developed T2DM (1.1% women, 2.1% men). Former smokers did not have statistically significant increased odds of IFG compared with smokers after adjustment for age, education, physical activity, hypercholesterolemia, hypertension and alcohol intake, with OR of 1.29 [95% confidence interval 0.94-1.76] for recent quitters and 1.03 [0.84-1.27] for long-term quitters. Former smokers did not have significant increased odds of T2DM compared with smokers with multivariable-adjusted OR of 1.53 [0.58-4.00] for recent quitters and 0.64 [0.27-1.48] for long-term quitters. Adjustment for body mass index and waist circumference attenuated the association between recent quitting and IFG (OR 1.07 [0.78-1.48]) and T2DM (OR 1.28 [0.48-3.40]. CONCLUSION: In this middle-aged population, smoking cessation was not associated with an increased risk of IFG or T2DM. PMID- 26547409 TI - Production of zinc and manganese oxide particles by pyrolysis of alkaline and Zn C battery waste. AB - Production of zinc and manganese oxide particles from alkaline and zinc-carbon battery black mass was studied by a pyrolysis process at 850-950 degrees C with various residence times under 1L/minN2(g) flow rate conditions without using any additive. The particular and chemical properties of the battery waste were characterized to investigate the possible reactions and effects on the properties of the reaction products. The thermodynamics of the pyrolysis process were studied using the HSC Chemistry 5.11 software. The carbothermic reduction reaction of battery black mass takes place and makes it possible to produce fine zinc particles by a rapid condensation, after the evaporation of zinc from a pyrolysis batch. The amount of zinc that can be separated from the black mass is increased by both pyrolysis temperature and residence time. Zinc recovery of 97% was achieved at 950 degrees C and 1h residence time using the proposed alkaline battery recycling process. The pyrolysis residue is mainly MnO powder with a low amount of zinc, iron and potassium impurities and has an average particle size of 2.9MUm. The obtained zinc particles have an average particle size of about 860nm and consist of hexagonal crystals around 110nm in size. The morphology of the zinc particles changes from a hexagonal shape to s spherical morphology by elevating the pyrolysis temperature. PMID- 26547410 TI - Technical assessment of processing plants as exemplified by the sorting of beverage cartons from lightweight packaging wastes. AB - The recovery of beverage cartons (BC) in three lightweight packaging waste processing plants (LP) was analyzed with different input materials and input masses in the area of 21-50Mg. The data was generated by gravimetric determination of the sorting products, sampling and sorting analysis. Since the particle size of beverage cartons is larger than 120mm, a modified sampling plan was implemented and targeted multiple sampling (3-11 individual samplings) and a total sample size of respectively 1200l (ca. 60kg) for the BC-products and of about 2400l (ca. 120kg) for material-heterogeneous mixed plastics (MP) and sorting residue products. The results infer that the quantification of the beverage carton yield in the process, i.e., by including all product-containing material streams, can be specified only with considerable fluctuation ranges. Consequently, the total assessment, regarding all product streams, is rather qualitative than quantitative. Irregular operation conditions as well as unfavorable sampling conditions and capacity overloads are likely causes for high confidence intervals. From the results of the current study, recommendations can basically be derived for a better sampling in LP-processing plants. Despite of the suboptimal statistical results, the results indicate very clear that the plants show definite optimisation potentials with regard to the yield of beverage cartons as well as the required product purity. Due to the test character of the sorting trials the plant parameterization was not ideal for this sorting task and consequently the results should be interpreted with care. PMID- 26547411 TI - An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection. AB - BACKGROUND: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. METHODS: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. RESULTS: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). CONCLUSION: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011). PMID- 26547412 TI - Which Individual Therapist Behaviors Elicit Client Change Talk and Sustain Talk in Motivational Interviewing? AB - OBJECTIVE: To identify individual therapist behaviors which elicit client change talk or sustain talk in motivational interviewing sessions. METHOD: Motivational interviewing sessions from a single-session alcohol intervention delivered to college students were audio-taped, transcribed, and coded using the Motivational Interviewing Skill Code (MISC), a therapy process coding system. Participants included 92 college students and eight therapists who provided their treatment. The MISC was used to code 17 therapist behaviors related to the use of motivational interviewing, and client language reflecting movement toward behavior change (change talk), away from behavior change (sustain talk), or unrelated to the target behavior (follow/neutral). RESULTS: Client change talk was significantly more likely to immediately follow individual therapist behaviors [affirm (p=.013), open question (p<.001), simple reflection (p<.001), and complex reflection (p<.001)], but significantly less likely to immediately follow others (giving information (p<.001) and closed question (p<.001)]. Sustain talk was significantly more likely to follow therapist use of open questions (p<.001), simple reflections (p<.001), and complex reflections (p<.001), and significantly less likely to occur following therapist use of therapist affirm (p=.012), giving information (p<.001), and closed questions (p<.001). CONCLUSIONS: Certain individual therapist behaviors within motivational interviewing can either elicit both client change talk and sustain talk or suppress both types of client language. Affirm was the only therapist behavior that both increased change talk and also reduced sustain talk. PMID- 26547413 TI - Development and characterization of 33 novel polymorphic microsatellite markers for the brown tree snake Boiga irregularis. AB - BACKGROUND: Boiga irregularis is a widespread invasive species on Guam and has led to extirpation of most of the island's native avifauna. There are presently no microsatellite markers for this invasive species, hence we developed highly polymorphic microsatellite markers to allow for robust population genetic studies on Guam. FINDINGS: We isolated and characterized 33 microsatellite loci for the brown tree snake, B. irregularis. The loci were screened across 32 individuals from Guam. The number of alleles per locus ranged from three to ten, with an average of 4.62. The expected (He) and observed heterozygosity (Ho) ranged from 0.294 to 0.856 and from 0.031 to 0.813, with an average of 0.648 and 0.524, respectively. Significant deviations from Hardy-Weinberg equilibrium were detected at seven loci after Bonferoni correction. Probability of identity values ranged from 0.043 to 0.539. CONCLUSIONS: These genetic markers are useful for understanding a suite of post-invasion population genetic parameters, sources of invasions, and effectiveness of management strategies for this invasive species. PMID- 26547414 TI - Growth and tolerance of formula with lactoferrin in infants through one year of age: double-blind, randomized, controlled trial. AB - BACKGROUND: Human milk provides necessary macronutrients (protein, carbohydrate, fat) required for infant nutrition. Lactoferrin (Lf), a multifunctional iron binding protein predominant in human milk, shares similar protein sequence, structure, and bioactivity with bovine Lf (bLf). This large-scale pediatric nutrition study was designed to evaluate growth and tolerance in healthy infants who received study formulas with bLf at concentrations within the range of mature human milk. METHODS: In this multi-center, double-blind, parallel-designed, gender-stratified prospective study 480 infants were randomized to receive a marketed routine cow's milk-based infant formula (Control; n = 155) or one of two investigational formulas with bLf at 0.6 g/L (LF-0.6; n = 165) or 1.0 g/L (LF 1.0; n = 160) from 14-365 days of age. Investigational formulas also had a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) and adjusted arachidonic acid (ARA). The primary outcome was weight growth rate from 14-120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, 120, 180, 275, and 365 days of age. Parental recall of formula intake, tolerance, and stool characteristics was collected at each time point. Medically-confirmed adverse events were collected throughout the study period. RESULTS: There were no group differences in growth rate (g/day) from 14-120 days of age; 353 infants completed the study through 365 days of age ( CONTROL: 110; LF-0.6: 127; LF-1.0: 116). Few differences in growth, formula intake, and infant fussiness or gassiness were observed through 365 day of age. Group discontinuation rates and the overall group incidence of medically-confirmed adverse events were not significantly different. From 30 through 180 days of age, group differences in stool consistency (P < 0.005) were detected with softer stools for infants in the LF-0.6 and LF-1.0 groups versus CONTROL. CONCLUSION: Compared to the Control, infants who received investigational formulas with bLf and the prebiotic blend of PDX and GOS experienced a softer stooling pattern similar to that reported in breastfed infants. This study demonstrated routine infant formulas with bLf, a blend of PDX and GOS, and adjusted ARA were safe, well-tolerated, and associated with normal growth when fed to healthy term infants through 365 days of age. TRIAL REGISTRATION: ClinicalTrials.gov NCT01122654 . Registered 10 May 2010. PMID- 26547415 TI - The use of Resonant X-ray Emission Spectroscopy (RXES) for the electronic analysis of metal complexes and their interactions with biomolecules. AB - This review presents a new application of Resonant X-ray Emission Spectroscopy (RXES) to study the mechanism of action of metal containing anticancer derivatives and in particular platinum in situ and in vivo. The technique is an example of a photon-in photon-out X-ray spectroscopic approach, which enables chemical speciation of drugs to be determined and therefore to derive action mechanisms, and to determine drug binding rates under physiological conditions and therapeutic concentrations. This is made feasible due to the atomic specificity and high penetration depth of RXES. The review presents examples of the three main types of information that can be obtained by RXES and establishes an experimental protocol to perfect the measurements within cells. PMID- 26547416 TI - Speciation of precious metal anti-cancer complexes by NMR spectroscopy. AB - Understanding the mechanism of action of anti-cancer agents is of paramount importance for drug development. NMR spectroscopy can provide insights into the kinetics and thermodynamics of the binding of metallodrugs to biomolecules. NMR is most sensitive for highly abundant I=1/2 nuclei with large magnetic moments. Polarization transfer can enhance NMR signals of insensitive nuclei at physiologically-relevant concentrations. This paper reviews NMR methods for speciation of precious metal anti-cancer complexes, including platinum-group and gold-based anti-cancer agents. Examples of NMR studies involving interactions with DNA and proteins in particular are highlighted. PMID- 26547417 TI - Capillary electrophoresis in metallodrug development. AB - Capillary electrophoresis (CE) is a separation method based on differential migration of analytes in electric fields. The compatibility with purely aqueous separation media makes it a versatile tool in metallodrug research. Many metallodrugs undergo ligand exchange reactions that can easily be followed with this method and the information gained can even be improved by coupling the CE to advanced detectors, such as mass spectrometers. This gives the method high potential to facilitate the development of metallodrugs, especially when combined with innovative method development and experimental design. PMID- 26547418 TI - Advanced LC-analysis of human plasma for metallodrug metabolites. AB - Understanding the fate of metallodrugs in the bloodstream is critical to assess if the parent drug has a reasonable probability to reach the intended target tissue and to predict toxic side-effects. To gain insight into these processes, we have added pharmacologically relevant doses of metallodrugs to blood plasma and applied an LC-method to directly analyze the latter for metallodrug metabolites. Using human or rabbit plasma, this LC-method was employed to gain insight into the metabolism of clinically used as well as emerging anticancer metallodrugs and to unravel the mechanisms by which small molecular weight compounds that - when co-administered with a metallodrug - decrease the toxic side-effects of the metallodrug by modulating its metabolism. The results suggest that the developed LC-method is useful to probe the fate of biologically active novel metal-complexes in plasma to help select those which may be advanced to animal/clinical studies to ultimately develop safer metallodrugs. PMID- 26547419 TI - Technologies to develop new metal medicines. PMID- 26547420 TI - A Simple Fluorescence Probe Based on Aggregation-Induced Emission (AIE) Property for the Detection of Mg(2+) Ions. AB - A simple aggregation-induced emission-based fluorescence probe (1) for Mg(2+) was synthesized by condensation of benzene-1, 2-diamine with 5-bromo-2 hydroxybenzaldehyde, This compound shows favourable character of the AIE-active molecules. More importantly, after addition of Mg(2+) to probe (1) in acetonitrile, the solution changed from colorless to yellow colour solution under ultraviolet (UV) radiation obtained from hand-held UV lamp, this finding suggested that probe (1) can be used to detect Mg(2+) by colorimetric detection. Detection limit can reach 2.31 * 10(-5) M(-1). The practical value of the selective and sensitive fluorescence indicators was confirmed by its application to detection of magnesium ion in acetonitrile. PMID- 26547421 TI - Synthesis and Photoluminescence Studies of Eu(III), Er(III) Doped Strontium Gadolinium Tantalum Oxide. AB - The luminescence properties of Sr2GdTaO6 have been studied by keeping Eu(3+) as constant concentration and varying Er(3+) concentration. Sr2GdTaO6 phosphor doped with rare earth ions of Eu and Er having monoclinic phase of space group P21/n was synthesized, and their photoluminescence properties have been examined under UV excitation of wavelength 265 nm and 275 nm. PL emission exhibited around 468, 475, 580, 596, and 610 nm wavelength subsequently for various concentrations of Er(3+) for two different excitation wavelengths. By using xenon lamp as source and corresponding wavelength having excitation wavelength 265 and 275 nm, it is observed that the maximum light emission yield in region presenting a color correlated temperature in the range of 1500-1900 K and 3000-6000 K. PMID- 26547422 TI - Concepts and Updates in the Evaluation and Diagnosis of Common Disorders of Sexual Development. AB - Our understanding of disorders of sexual differentiation (DSD) has evolved from aberrations of human genital development to a broad group of complex disorders of etiological and functional significance. The unique challenge of DSD conditions is that they create a cause for significant angst and concern for both parents and physician, as they frequently lead to questions with regards to gender assignment, surgically corrective options, long-term outlook regarding gender identity, and reproductive potential. To further add to the burden, many patients who present with genital abnormalities do not have a clear explanation as to the underlying basis of their disorder. This review looks at DSD from a pediatric urology point of view with emphasis on evaluation, diagnosis, and algorithm for work-up. We also discuss novel genetic analysis techniques and their value in diagnosis. Overall, this is an all-encompassing review on a diagnostic approach to DSD, with inclusion of recent developments and controversies, which will benefit urologists and other physicians alike. PMID- 26547423 TI - Health insurance status and survival among patients with head and neck cancer in Japan. AB - BACKGROUND: Healthcare systems vary among countries, and in many countries, insurance and economic statuses significantly impact the mortality associated with head and neck squamous cell carcinoma (HNSCC). Japan prides itself on its unique healthcare and health insurance system, which provides equal coverage and healthcare access with low individual payments to most citizens. Additionally, citizens in poverty are covered by insurance for the poor (public assistance) and receive medical and other types of assistance. Hence, they have no barriers to healthcare services. This study aimed to determine the impact of health insurance status on mortality in Japanese patients with HNSCC. METHODS: We reviewed 409 patients with HNSCC, using the Kaplan-Meier method to estimate overall survival. The association between insurance status and disease stage at diagnosis was analyzed via logistic regression. Cox and Fine-Gray proportional hazard models were employed to investigate the impact of insurance status on survival. RESULTS: The public assistance and other insurances groups did not significantly differ in clinical stage distribution. The 5-year overall survival, cumulative incidence of HNSCC death, and cumulative incidence of other death rates were 63.3 and 59.1 %, 27.0 and 31.8 %, and 10.3 and 9.7 % for the public assistance and other insurances groups, respectively. The adjusted subdistribution hazard ratio for the association between public assistance and HNSCC death was 0.73 (95 % confidence interval 0.44-1.21). CONCLUSIONS: The demonstrated non-inferiority of public assistance regarding HNSCC-specific mortality indicates the equality of healthcare in Japan, irrespective of the insurance status, and the superiority of the Japanese healthcare system. PMID- 26547424 TI - Phase II multi-institutional prospective randomized trial comparing S-1 plus paclitaxel with paclitaxel alone as second-line chemotherapy in S-1 pretreated gastric cancer (CCOG0701). AB - BACKGROUND: The aim of this study was to explore whether a combination of S-1 and paclitaxel offers any benefit over paclitaxel alone to patients pretreated by S 1. METHODS: Gastric cancer patients who developed progression during S-1-based first-line chemotherapy or had recurrence during postoperative adjuvant chemotherapy by S-1 were randomly assigned to receive second-line treatment either by weekly administration of paclitaxel at 80 mg/m(2) three times every 4 weeks or daily oral S-1 (80 mg/m(2)) for 2 weeks plus paclitaxel (50 mg/m(2)) given on days 1 and 8, every 3 weeks (S-1 plus paclitaxel). The primary endpoint was progression-free survival (PFS) at 4 months after the initiation of treatment. RESULTS: A total of 78 patients were eligible for efficacy analyses-40 were assigned to the paclitaxel group and 38 to the S-1 plus paclitaxel group. PFS at 4 months was similar between the groups (50 % for paclitaxel vs 55 % for S 1 plus paclitaxel, P = 0.641). There were no differences between the groups either in progression-free survival (4.6 vs 4.6 months, respectively, P = 0.526), overall survival (10.0 vs 10.0 months, respectively, P = 0.464), or overall response rate (27 vs 22 %, respectively, P = 0.767). The incidences of grade 3 or 4 hematological and non-hematological toxicities were also equivalent between the two groups (25 vs 26 % and 24 vs 26 %, respectively). CONCLUSIONS: No benefit of S-1 administration beyond progression was shown when paclitaxel was selected as the key drug for second-line chemotherapy. PMID- 26547425 TI - Does Guanfacine Extended Release Impact Functional Impairment in Children with Attention-Deficit/Hyperactivity Disorder? Results from a Randomized Controlled Trial. AB - BACKGROUND: In clinical trials of medications to treat attention deficit/hyperactivity disorder (ADHD) in children, effects on functional impairment have been less well-studied than changes in ADHD symptoms. OBJECTIVE: Data regarding functional impairment were analyzed from a multicenter, double blind, placebo-controlled study of guanfacine extended release (GXR) in children with ADHD, using the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). The correspondence of changes in WFIRS-P scores with symptomatic and global response to GXR treatment was also examined, with treatment response defined by scores on both the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impressions-Improvement Scale (CGI-I). METHODS: In this 8-week, double blind, placebo-controlled, dose optimization study at 47 sites across the USA and Canada, children aged 6-12 years with a diagnosis of ADHD [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and an ADHD-RS-IV score >=28 and CGI-Severity of Illness Scale score >=4 at baseline], were randomized 1:1:1 into three groups: GXR AM [GXR (1-4 mg/day) in the morning, placebo in the evening], GXR PM [placebo in the morning, GXR (1-4 mg/day) in the evening], or twice-daily placebo. Parents rated their children on the WFIRS-P at screening, baseline, the end of dose optimization, and at the final on-treatment assessment. RESULTS: The efficacy population was composed of 333 subjects (GXR AM: n = 107; GXR PM: n = 114; placebo: n = 112). At the final on-treatment assessment, there were significant improvements from baseline in the placebo-adjusted difference in least-squares (LS) mean (95 % confidence interval) WFIRS-P Total scores for both GXR treatment groups combined [GXR all-active: 0.16 (-0.25, -0.07), effect size (ES) = 0.448, P <0.001] and separately [GXR AM: 0.15 (-0.26, -0.05), ES = 0.417, P = 0.004; GXR PM: -0.18 (-0.28, -0.07), ES = 0.478, P = 0.001]. Significant improvements in WFIRS-P domain scores for Family, Learning and School (including Academic Performance and Behavior in School), Social, and Risky Behavior were found for both GXR cohorts compared with placebo. However, the Life Skills and Self-Concept domain scores of the WFIRS-P did not improve with GXR treatment. Post hoc stratification by responder status revealed that significant (P <0.001) improvements in WFIRS-P Total and all domain scores were associated with symptomatic treatment response in the GXR all-active group. CONCLUSIONS: GXR treatment in children with ADHD was associated with reductions in WFIRS-P functional impairment scores compared with placebo, regardless of time of GXR administration. Changes in WFIRS-P scores were congruent with clinical response, as determined by both ADHD symptom reduction and CGI-I scores. CLINICALTRIALS. GOV IDENTIFIER: NCT00997984. PMID- 26547426 TI - Graphene oxide-gold nanoparticles hybrids-based surface plasmon resonance for sensitive detection of microRNA. AB - In this study, a simple and sensitive surface plasmon resonance (SPR) biosensor for miRNA detection was developed using graphene oxide-gold nanoparticles (GO AuNPs) hybrids as signal amplification element. Taking advantage of the GO-AuNPs hybrids and their enhanced performance in SPR biosensors, the detection of miRNA was carried out in only two steps. Firstly, the thiolated capture DNA probe with a short complete complementary sequence was immobilized on the Au film surface to recognize the part sequence of target miRNA. Subsequently, the assistant DNA linked GO-AuNPs hybrids were employed to bind the other section of the target. It was found that the developed SPR biosensor was able to achieve a detection limit as low as 1 fM. Moreover, the method showed excellent ability to discriminate differences among miRNA-200 family members. Notably, human miRNA from cancer cells could also be detected, and the results were in excellent agreement with the ones obtained using qRT-PCR. On the basis of these findings, we believe that this method has great potential for quantitative detection of miRNA in biomedical research and early clinical diagnostics. PMID- 26547427 TI - High-performance and high-sensitivity applications of graphene transistors with self-assembled monolayers. AB - Charge impurities and polar molecules on the surface of dielectric substrates has long been a critical obstacle to using graphene for its niche applications that involve graphene's high mobility and high sensitivity nature. Self-assembled monolayers (SAMs) have been found to effectively reduce the impact of long-range scatterings induced by the external charges. Yet, demonstrations of scalable device applications using the SAMs technique remains missing due to the difficulties in the device fabrication arising from the strong surface tension of the modified dielectric environment. Here, we use patterned SAM arrays to build graphene electronic devices with transport channels confined on the modified areas. For high-mobility applications, both rigid and flexible radio-frequency graphene field-effect transistors (G-FETs) were demonstrated, with extrinsic cutoff frequency and maximum oscillation frequency enhanced by a factor of ~2 on SiO2/Si substrates. For high sensitivity applications, G-FETs were functionalized by monoclonal antibodies specific to cancer biomarker chondroitin sulfate proteoglycan 4, enabling its detection at a concentration of 0.01 fM, five orders of magnitude lower than that detectable by a conventional colorimetric assay. These devices can be very useful in the early diagnosis and monitoring of a malignant disease. PMID- 26547428 TI - Sensing and antibacterial activity of imidazolium-based conjugated polydiacetylenes. AB - In the current study, we report the first example of polydiacetylenes (PDAs), where our PDA-based system acts as both a sensing probe and killer for bacteria. The contact of imidazolium and imidazole-derived PDA with various bacterial strains including MRSA (methicillin-resistant Staphylococcus aureus) and ESBL-EC (extended-spectrum beta-lactamase-producing Escherichia coli) results in a distinct blue-to-red colorimetric change of the solution as well as a rapid disruption of the bacterial membrane, which is demonstrated by transmission electron microscopy and confocal microscopy. Zeta potential analysis supports that antibacterial activity of the PDA solution originates from an electrostatic interaction between the negatively charged bacterial cell surface and the positively charged polymers. These results suggest that the PDA has a great potential to carry out the dual roles of a probe and killer for bacteria. PMID- 26547429 TI - Rapid detection of acute myocardial infarction-related miRNA based on a Capture interCalation-electroCatalysis (3C) strategy. AB - Acute myocardial infarction (AMI) is one of the most urgent and serious diseases that may cause cardiac death in a few hours. Rapid diagnosis of AMI is the pre requisite for timely interventions. Recently, several specific circulating miRNAs have been proven to have high correlation with AMI. To adopt miRNA as a biomarker may improve the diagnostic accuracy. However, it is a pity that the current available methods for the detection of miRNA usually require a few hours, which is too long for the diagnosis of AMI. In this paper, by adopting a capture DNA, an electrochemical active intercalator and an unimmobilized enzyme, we develop a Capture-interCalation-electroCatalysis (3C) strategy for the rapid detection of AMI-related miRNA. The whole detection process can be completed in 35 min, which is much shorter than most current methods and is acceptable for the diagnosis of AMI. This strategy also shows favorable sensitivity and selectivity, thus provides an alternative for the detection of miRNA. Most importantly, this effort may promote miRNA to work as an effective biomarker in the diagnosis of AMI. PMID- 26547430 TI - A fluorogenic substrate of beta-lactamases and its potential as a probe to detect the bacteria resistant to the third-generation oxyimino-cephalosporins. AB - We devised and synthesized a fluorogenic substrate of beta-lactamases as a probe to detect the activity of the enzymes. Fluorescence of the probe emitted upon treatment of a beta-lactamase and increased proportionally to the concentration of the enzyme, demonstrating its sensing property for the activity of the enzyme. We also showed that the probe could be utilized to assay the enzyme and to determine kinetic parameters of the enzyme. Moreover, the probe was able to detect resistance to the third-generation oxyimino-cephalosporin-derived antibiotics such as cefotaxime and ceftazidime. In particular, the probe could identify the ceftazidime-resistance in bacteria that was not detectable using conventional pH-sensing materials, indicating the practical utility of the probe. PMID- 26547431 TI - Generation and characterization of quinolone-specific DNA aptamers suitable for water monitoring. AB - Quinolones are antibiotics that are accredited in human and veterinary medicine but are regularly used in high quantities also in industrial livestock farming. Since these compounds are often only incompletely metabolized, significant amounts contaminate the aquatic environment and negatively impact on a variety of different ecosystems. Although there is increasing awareness of problems caused by pharmaceutical pollution, available methods for the detection and elimination of numerous pharmaceutical residues are currently inefficient or expensive. While this also applies to antibiotics that may lead to multi-drug resistance in pathogenic bacteria, aptamer-based technologies potentially offer alternative approaches for sensitive and efficient monitoring of pharmaceutical micropollutants. Using the Capture-SELEX procedure, we here describe the selection of an aptamer pool with enhanced binding qualities for fluoroquinolones, a widely used group of antibiotics in both human and veterinary medicine. The selected aptamers were shown to detect various quinolones with high specificity, while specific binding activities to structurally unrelated drugs were not detectable. The quinolone-specific aptamers bound to ofloxacin, one of the most frequently prescribed fluoroquinolone, with high affinity (KD=0.1-56.9 nM). The functionality of quinolone-specific aptamers in real water samples was demonstrated in local tap water and in effluents of sewage plants. Together, our data suggest that these aptamers may be applicable as molecular receptors in biosensors or as catcher molecules in filter systems for improved monitoring and treatment of polluted water. PMID- 26547432 TI - In situ monitoring of myenteric neuron activity using acetylcholinesterase modified AlGaN/GaN solution-gate field-effect transistors. AB - The response characteristics of acetylcholinesterase-modified AlGaN/GaN solution gate field-effect transistors (AcFETs) are quantitatively analyzed by means of a kinetic model. The characterization shows that the covalent enzyme immobilization process yields reproducible AcFET characteristics with a Michaelis constant KM of (122 +/- 4) MUM for the immobilized enzyme layer. The increase of KM by a factor of 2.4 during the first four measurement cycles is attributed to partial denaturation of the enzyme. The AcFETs were used to record the release of acetylcholine (ACh) by neuronal tissue cultivated on the gate area upon stimulation by rising the extracellular K(+) concentration. The neuronal tissue constituted of isolated myenteric neurons from four to 12 days old Wistar rats, or sections from the muscularis propria containing the myenteric plexus from adult rats. For both cases the AcFET response was demonstrated to be related to the activity of the immobilized acetylcholinesterase using the reversible acetylcholinesterase blocker donepezil. A concentration response curve of this blocking agent revealed a half maximal inhibitory concentration of 40 nM which is comparable to values measured by complementary in vitro methods. PMID- 26547433 TI - Functionalized gold nanoclusters as fluorescent labels for immunoassays: Application to human serum immunoglobulin E determination. AB - A quantitative immunoassay for the determination of immunoglobulin E (IgE) in human serum using gold nanoclusters (AuNCs) as fluorescent label was developed. Water soluble AuNCs were synthesized using lipoic acid and then thoroughly characterized. The obtained AuNCs have a particle size of 2.7 +/- 0.1 nm and maximum fluorescence emission at 710 nm. The synthesized AuNCs showed very good stability of the fluorescent signal with light exposure and at neutral and slightly basic media. A covalent bioconjugation of these AuNCs with the desired antibody was carried out by the carbodiimide reaction. After due optimization of such bioconjugation reaction, a molar ratio 1:3 (antibody:AuNCs) was selected. The bioconjugate maintained an intense luminescence emission, slightly red shifted as compared to the free AuNCs. Two typical immunoassay configurations, competitive and sandwich, were assayed and their performance for IgE determination critically compared. After the different immunoassay steps were accomplished, the fluorescence emission of the bioconjugate was measured. While the sandwich format provided a detection limit (DL) of 10 ng/mL and a linear range between 25 and 565 ng/mL of IgE, the competitive format revealed a DL of 0.2 ng/mL with a linear range between 0.3 and 7.1 ng/mL The applicability of the more sensitive competitive fluorescent immunoassay was assessed by successful analysis of the IgE in human serum and comparison of results with those from a commercial kit. The main advantages of the proposed AuNCs-based fluorimetric method include a low DL and a simple immunoassay protocol involving few reagents. PMID- 26547434 TI - First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia. AB - Antipsychotic medication may influence brain structure, but to what extent effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) differ is still not clear. Here we aimed to disentangle the effects of FGA and SGA on variation in volumes of subcortical structures in patients with long-term treated schizophrenia. Magnetic resonance images were obtained from 95 patients with schizophrenia and 106 healthy control subjects. Among the patients, 40 received only FGA and 42 received only SGA. FreeSurfer 5.3.0 was used to obtain volumes of 27 subcortical structures as well as total brain volume and estimated intracranial volume. Findings of reduced total brain volume, enlarged ventricular volume and reduced hippocampal volume bilaterally among patients were replicated, largely independent of medication class. In the basal ganglia, FGA users had larger putamen bilaterally and right caudate volume compared to healthy controls, and the right putamen was significantly larger than among SGA users. FGA and SGA users had similar and larger globus pallidus volumes compared to healthy controls. Post hoc analyses revealed that the difference between FGA and SGA could be attributed to smaller volumes in the clozapine users specifically. We therefore conclude that basal ganglia volume enlargements are not specific to FGA. PMID- 26547435 TI - Adjuvant chemotherapy for soft tissue sarcomas: a 10-year mono-institutional experience. AB - PURPOSE: The role of adjuvant chemotherapy (ACT) for soft tissue sarcomas (STS) is not standard practice. We investigated effectiveness and tolerability of ACT in patients (pts) with operated high-risk STS in clinical practice. METHODS: Medical records of pts with localized STS referred to Istituto Oncologico Veneto, Padova, from January 1, 2003 to July 07, 2012 were reviewed. Data were collected for pts with high-risk STS (size >=5 cm, high grade and stage III). For those who received ACT, regimens used, drug doses, number of cycles, toxicity, and reasons for dose reduction or treatment interruption were recorded. Disease-free survival (DFS) and overall survival (OS) were calculated with the Kaplan-Meier method. RESULTS: Out of 96 eligible pts, median age 62 years, 36 received ACT after loco regional treatment. Median DFS was 29.6 months (95 % CI 13.2-46.0) in pts receiving ACT and 7.8 months (95 % CI 3.9-11.7) in untreated pts (p < 0.0001); median OS was 67.0 months (95 % CI 25.4-108.6) in treated and 33.7 months (95 % CI 23.3-44.2) in untreated pts (p = 0.005). Among pts receiving ACT, a significant difference in DFS was observed between pts with limb/girdle disease (median DFS 82.4 months; 95 % CI 0.0-184.7) and pts with other primary sites (median DFS 18.3 months; 95 % CI 8.0-28.5) (p = 0.052). Grade >=3 toxicities occurred in 20 pts (20.8 %), leading to dose reductions, delays, and treatment discontinuation in five cases. There was no treatment-related death. CONCLUSION: Our data confirm benefit of ACT with regard to DFS and OS in pts with high-risk STS, greatest for limb/girdle STS. PMID- 26547436 TI - Effect of Inhaled Nitric Oxide on Blood Flow Dynamics in Patients After the Fontan Procedure Using Cardiovascular Magnetic Resonance Flow Measurements. AB - Invasive hemodynamic studies have shown that nitric oxide (NO), a selective pulmonary vasodilator, can lower pulmonary vascular resistance in Fontan patients. Because oximetry-derived flow quantification may be unreliable, we sought to detect changes in blood flow within the Fontan circulation after inhalation of NO using cardiovascular magnetic resonance (CMR). Thirty-three patients (mean age 12.8 +/- 7.0 years) after the Fontan procedure underwent CMR as part of their routine clinical assessment. Standard two-dimensional blood flow measurements were performed in the Fontan tunnel, superior vena cava (SVC) and ascending aorta (AAO) before and after inhalation of 40 ppm NO for 8-10 min. Systemic-to-pulmonary collateral (SPC) flow was calculated as AAO - (SVC + tunnel). Heart rate (82 +/- 18 to 81 +/- 18 bpm; p = 0.31) and transcutaneous oxygen saturations (93 +/- 4 to 94 +/- 3 %; p = 0.13) did not change under NO inhalation. AAO flow (3.23 +/- 0.72 to 3.12 +/- 0.79 l/min/m(2); p = 0.08) decreased, tunnel flow (1.58 +/- 0.40 to 1.65 +/- 0.46 l/min/m(2); p = 0.032) increased, and SVC flow (1.01 +/- 0.39 to 1.02 +/- 0.40 l/min/m(2); p = 0.50) remained unchanged resulting in higher total caval flow (Qs) (2.59 +/- 0.58 to 2.67 +/- 0.68 l/min/m(2); p = 0.038). SPC flow decreased significantly from 0.64 +/- 0.52 to 0.45 +/- 0.51 l/min/m(2) (p = 0.002) and resulted in a significant decrement of the Qp/Qs ratio (1.23 +/- 0.23 to 1.15 +/- 0.23; p = 0.001). Inhalation of NO in Fontan patients results in significant changes in pulmonary and systemic blood flow. The reduction in SPC flow is accompanied by a net increase in effective systemic blood flow suggesting beneficial effects of pulmonary vasodilators on cardiac output, tissue perfusion and exercise capacity. PMID- 26547437 TI - 1H, 13C and 15N resonance assignments and secondary structure analysis of CmPI II, a serine protease inhibitor isolated from marine snail Cenchritis muricatus. AB - A protease inhibitor (CmPI-II) (UNIPROT: IPK2_CENMR) from the marine mollusc Cenchritis muricatus, has been isolated and characterized. It is the first member of a new group (group 3) of non-classical Kazal-type inhibitors. CmPI-II is a tight-binding inhibitor of serine proteases: trypsin, human neutrophil elastase (HNE), subtilisin A and pancreatic elastase. This specificity is exceptional in the members of Kazal-type inhibitor family. Several models of three-dimensional structure of CmPI-II have been constructed by homology with other inhibitors of the family but its structure has not yet been solved experimentally. Here we report the (1)H, (15)N and (13)C chemical shift assignments of CmPI-II as basis for NMR structure determination and interaction studies. Secondary structure analyses deduced from the NMR chemical shift data have identified three beta strands beta1: residues 14-19, beta2: 23-35 and beta3: 43-45 and one helix alpha1: 28-37 arranged in the sequential order beta1-beta2-alpha1-beta3. These secondary structure elements suggest that CmPI-II adopts the typical scaffold of a Kazal-type inhibitor. PMID- 26547438 TI - Aberrant membranous expression of beta-catenin predicts poor prognosis in patients with craniopharyngioma. AB - The objective of this study is to investigate beta-catenin expression in craniopharyngioma patients and determine its significance in predicting the prognosis of this disease. Fifty craniopharyngioma patients were enrolled in this study. Expression of beta-catenin in tumor specimens collected from these patients was examined through immunostaining. In addition, mutation of exon 3 in the beta-catenin gene, CTNNB1, was analyzed using polymerase chain reaction, denaturing high-pressure liquid chromatography, and DNA sequencing. Based on these results, we explored the association between membranous beta-catenin expression, clinical and pathologic characteristics, and prognoses in these patients. Of all craniopharyngioma specimens, 31 (62.0%) had preserved membranous beta-catenin expression, whereas the remaining 19 specimens (38.0%) displayed aberrant expression. Statistical analysis showed a significant correlation between aberrant membranous beta-catenin expression and CTNNB1 exon 3 mutation, as well as between aberrant membranous beta-catenin expression and the histopathologic type of craniopharyngioma and type of resection in our patient population. Furthermore, aberrant membranous beta-catenin expression was found to be associated with poor patient survival. Results of Kaplan-Meier survival analysis and Cox regression analysis further confirmed this finding. In conclusion, our study demonstrated that aberrant membranous beta-catenin expression was significantly correlated with poor survival in patients with craniopharyngioma. This raises the possibility for use of aberrant membranous beta-catenin expression as an independent risk factor in predicting the prognosis of this disease. PMID- 26547439 TI - Correlation between the germline methylation status in ERbeta promoter and the risk in prostate cancer: a prospective study. AB - Familial aggregation of cancer may reflect an overall contribution of inherited genes or a shared mechanism for the manipulation of gene function. DNA methylation in the promoter regions is considered to be a mechanism through which tumor suppressor genes are inhibited, which will lead to tumorigenesis and tumor progression. To evaluate the association between the methylation status in the promoter of estrogen receptor (ER) beta,possibly a tumor suppressor gene specific for prostate cancer, and the risk in prostate cancer in a Chinese population, a case-control study that included 56 sporadic prostate cancer cases and 60 healthy controls was conducted. Genomic DNA was extracted from peripheral blood of all the subjects for analyzing the methylation status of the ERbeta promoter by methylation-specific PCR, which was verified by bisulfite genomic sequencing PCR. A significant difference was observed in the methylation frequencies of the ERbeta promoter between cancer patients (12/56, 21.4%) and healthy controls (5/60, 8.3%). Prostate cancer (PC-3 and DU-145) and prostatic epithelial (RWPE-1) cell lines were treated with various concentrations of the methyltransferase inhibitor 5-Aza-2'-dC. Expression of ERbeta was detected at both transcriptional and translational levels. As a result, both mRNA and protein of ERbeta were elevated following treatment with increasing concentrations of the demethylating agent. Taken together, our results support the conclusion that abnormal methylation of the ERbeta promoter may increase genetic susceptibility to prostate cancer. PMID- 26547440 TI - Ectomycorrhizal communities of ponderosa pine and lodgepole pine in the south central Oregon pumice zone. AB - Forest ecosystems of the Pacific Northwest of the USA are changing as a result of climate change. Specifically, rise of global temperatures, decline of winter precipitation, earlier loss of snowpack, and increased summer drought are altering the range of Pinus contorta. Simultaneously, flux in environmental conditions within the historic P. contorta range may facilitate the encroachment of P. ponderosa into P. contorta territory. Furthermore, successful pine species migration may be constrained by the distribution or co-migration of ectomycorrhizal fungi (EMF). Knowledge of the linkages among soil fungal diversity, community structure, and environmental factors is critical to understanding the organization and stability of pine ecosystems. The objectives of this study were to establish a foundational knowledge of the EMF communities of P. ponderosa and P. contorta in the Deschutes National Forest, OR, USA, and to examine soil characteristics associated with community composition. We examined EMF root tips of P. ponderosa and P. contorta in soil cores and conducted soil chemistry analysis for P. ponderosa cores. Results indicate that Cenococcum geophilum, Rhizopogon salebrosus, and Inocybe flocculosa were dominant in both P. contorta and P. ponderosa soil cores. Rhizopogon spp. were ubiquitous in P. ponderosa cores. There was no significant difference in the species composition of EMF communities of P. ponderosa and P. contorta. Ordination analysis of P. ponderosa soils suggested that soil pH, plant-available phosphorus (Bray), total phosphorus (P), carbon (C), mineralizable nitrogen (N), ammonium (NH4), and nitrate (NO3) are driving EMF community composition in P. ponderosa stands. We found a significant linear relationship between EMF species richness and mineralizable N. In conclusion, P. ponderosa and P. contorta, within the Deschutes National Forest, share the same dominant EMF species, which implies that P. ponderosa may be able to successfully establish within the historic P. contorta range and dominant EMF assemblages may be conserved. PMID- 26547442 TI - Ammonia concentrations in different size classes of ovarian follicles of sheep (Ovis aries): Possible mechanisms of accumulation and its effect on oocyte and granulosa cell growth in vitro. AB - The present study investigated the concentrations and the mechanisms of accumulation of ammonia in different sizes of ovarian follicles and the effect of ammonia on oocyte and granulosa cell growth and functions in vitro with sheep (Ovis aries) as an animal model. The effects of cyclicity, seasonality, phases of the estrous cycle, and seasons (environmental) on ammonia concentrations in follicular fluid were also investigated. The effect of ammonia on in vitro development of oocytes (maturation rate, viability rate, cleavage rate, morulae/blastocysts yield) recovered from different sizes of follicles was examined at the levels of 0, 50, 100, 150, 250, 300, and 500 MUM. Same concentrations of ammonia were examined on growth parameters (metabolic activity, viability, cell number increment, monolayer formation, apoptosis rate) and hormone (progesterone, estrogen) secretion activity of granulosa cells in vitro. Results suggested as the follicle size increased, ammonia concentrations decreased. The ammonia concentrations in ovine follicular fluid were found to be 261.5 +/- 32.4, 157.7 +/- 19.2, and 42.9 +/- 8.3 MUM, respectively, for small, medium, and large follicles. The corresponding ranges were 290 to 238 MUM, 184 to 142 MUM, and 70 to 22 MUM. The differences were due to more accumulation of fluid, less metabolic activity of granulosa cells, and elevation of protein, potassium, and chloride as the follicle size increased. The seasonality and phases of the estrous cycle did not have any effect on ammonia level in ovarian follicles. Ammonia concentrations in all size classes of follicles examined were significantly reduced in ewes during hot seasons compared to cold seasons and in acyclic animals compared to cyclic ones. Ammonia impaired oocyte development at 300 MUM when the oocytes were isolated from small follicles and at 250 MUM when the oocytes were isolated from medium and large follicles. In contrast, ammonia caused the negative impact on granulosa cells growth and secretary activity at 250 MUM when the cells were isolated from small and medium follicles and at 150 MUM when the cells were isolated from large follicles. PMID- 26547441 TI - Impact of clinical osteoarthritis of the hip, knee and hand on self-rated health in six European countries: the European Project on OSteoArthritis. AB - PURPOSE: Osteoarthritis (OA) has been shown to be associated with decreased physical function, which may impact upon a person's self-rated health (SRH). Only a few studies have examined the association between OA and SRH in the general population, but to date none have used a clinical definition of OA. The objectives are: (1) To examine the cross-sectional association between clinical OA and fair-to-poor SRH in the general population; (2) To examine whether this association differs between countries; (3) To examine whether physical function is a mediator in the association between clinical OA and SRH. METHODS: Baseline data of the European Project on OSteoArthritis (EPOSA) were used, which includes pre-harmonized data from six European cohort studies (n = 2709). Clinical OA was defined according to the American College of Rheumatology criteria. SRH was assessed using one question: How is your health in general? Physical function was assessed using the Western Ontario and McMaster Universities OA Index and Australian/Canadian OA Hand Index. RESULTS: The prevalence of fair-to-poor SRH ranged from 19.8 % in the United Kingdom to 63.5 % in Italy. Although country differences in the strength of the associations were observed, clinical OA of the hip, knee and hand were significantly associated with fair-to-poor SRH in five out of six European countries. In most countries and at most sites, the association between clinical OA and fair-to-poor SRH was partly or fully mediated by physical function. CONCLUSIONS: Clinical OA at different sites was related to fair-to-poor SRH in the general population. Most associations were (partly) mediated by physical functioning, indicating that deteriorating physical function in patients with OA should be a point of attention in patient care. PMID- 26547444 TI - Immuno-capture of UVDE generated 3'-OH ends at UV photoproducts. AB - A strategy amenable to the genome-wide study of DNA damage and repair kinetics is described. The ultraviolet damage endonuclease (UVDE) generates 3'-OH ends at the two major UV induced DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6,4 pyrimidine-pyrimidone dimers (6,4 PPs), allowing for their capture after biotin end-labeling. qPCR amplification of biotinylated DNA enables parallel measuring of DNA damage in several loci, which can then be combined with high-throughput screening of cell survival to test genotoxic reagents. Alternatively, a library of captured sequences could be generated for a genome wide study of damage sites and large-scale assessment of repair kinetics in different regions of the genome, using next-generation sequencing. The assay is suitable to study any DNA lesion that can be converted into 3'-OH by UVDE, or other enzymes. Toward these goals, we compared UVDE with the classical T4 endonuclease V (T4V) assay. We showed that there is a linear correlation between UV dose, 3'-OH formation and capture by immunoprecipitation, together with its potential application for in vivo studies. PMID- 26547443 TI - Wnt5a reverses the inhibitory effect of hyperoxia on transdifferentiation of alveolar epithelial type II cells to type I cells. AB - Transdifferentiation of alveolar epithelial type II cells (AECIIs) to type I cells (AECIs) is critical for reestablishment and maintenance of an intact alveolar epithelium. However, this process is frequently destroyed by hyperoxia treatment, which is commonly used in respiratory distress syndrome therapy in preterm infants. Wnt5a is considered to participate in this physiopathologic process, but the clear mechanisms still need to be further investigated. In this study, preterm rats and primary rat AECIIs were exposed to hyperoxia. Hematoxylin and eosin staining was used to examine the histological changes of the lungs. Real-time PCR and western blotting were used to examine Wnt5a expression and biomarkers of AECII and AECI expression. Immunohistochemistry and immunofluorescence were also used to determine the expression and location of selected biomarkers. Furthermore, AECIIs transfected with Wnt5a gene and exogenous Wnt5a were used to examine whether Wnt5a contributes to the transdifferentiation of AECIIs to AECIs. Results showed that hyperoxia inhibited the transdifferentiation of AECIIs to AECIs in vitro, which is represented by biomarkers of two types of cell that remained unchanged. In addition, Wnt5a protein expression was found to be decreased after hyperoxia exposure in vitro and in vivo. Furthermore, both the overexpression of Wnt5a and exogenous Wnt5a addition blocked the inhibitory effect of hyperoxia in vitro. In conclusion, our results suggest that the transdifferentiation of AECIIs to AECIs is impaired by hyperoxia, and this process may be associated with Wnt5a downregulation. Targeting Wnt5a may have the potential for the therapy of lung injury in preterm infants induced by hyperoxia. PMID- 26547447 TI - Untitled: Stephen Gilbert. PMID- 26547448 TI - NHSC Students to Service Awardees Begin Residencies. PMID- 26547456 TI - Predicting the Overuse of PCSK-9 Inhibitors. PMID- 26547457 TI - Asymptomatic Atrial Fibrillation: The Case for Screening to Prevent Stroke. PMID- 26547458 TI - Improving Awareness and Outcomes Related to Venous Thromboembolism. PMID- 26547459 TI - Exercise Is Medicine: At Any Dose? PMID- 26547460 TI - Evidence-Based Management of Stable Ischemic Heart Disease: Challenges and Confusion. PMID- 26547461 TI - A piece of my mind. What Now? PMID- 26547462 TI - Erasing Disability in Peripheral Artery Disease: The Role of Endovascular Procedures and Supervised Exercise. PMID- 26547463 TI - Advancing Cardiovascular Science. PMID- 26547464 TI - Effect of Financial Incentives to Physicians, Patients, or Both on Lipid Levels: A Randomized Clinical Trial. AB - IMPORTANCE: Financial incentives to physicians or patients are increasingly used, but their effectiveness is not well established. OBJECTIVE: To determine whether physician financial incentives, patient incentives, or shared physician and patient incentives are more effective than control in reducing levels of low density lipoprotein cholesterol (LDL-C) among patients with high cardiovascular risk. DESIGN, SETTING, AND PARTICIPANTS: Four-group, multicenter, cluster randomized clinical trial with a 12-month intervention conducted from 2011 to 2014 in 3 primary care practices in the northeastern United States. Three hundred forty eligible primary care physicians (PCPs) were enrolled from a pool of 421. Of 25,627 potentially eligible patients of those PCPs, 1503 enrolled. Patients aged 18 to 80 years were eligible if they had a 10-year Framingham Risk Score (FRS) of 20% or greater, had coronary artery disease equivalents with LDL-C levels of 120 mg/dL or greater, or had an FRS of 10% to 20% with LDL-C levels of 140 mg/dL or greater. Investigators were blinded to study group, but participants were not. INTERVENTIONS: Primary care physicians were randomly assigned to control, physician incentives, patient incentives, or shared physician-patient incentives. Physicians in the physician incentives group were eligible to receive up to $1024 per enrolled patient meeting LDL-C goals. Patients in the patient incentives group were eligible for the same amount, distributed through daily lotteries tied to medication adherence. Physicians and patients in the shared incentives group shared these incentives. Physicians and patients in the control group received no incentives tied to outcomes, but all patient participants received up to $355 each for trial participation. MAIN OUTCOMES AND MEASURES: Change in LDL-C level at 12 months. RESULTS: Patients in the shared physician patient incentives group achieved a mean reduction in LDL-C of 33.6 mg/dL (95% CI, 30.1-37.1; baseline, 160.1 mg/dL; 12 months, 126.4 mg/dL); those in physician incentives achieved a mean reduction of 27.9 mg/dL (95% CI, 24.9-31.0; baseline, 159.9 mg/dL; 12 months, 132.0 mg/dL); those in patient incentives achieved a mean reduction of 25.1 mg/dL (95% CI, 21.6-28.5; baseline, 160.6 mg/dL; 12 months, 135.5 mg/dL); and those in the control group achieved a mean reduction of 25.1 mg/dL (95% CI, 21.7-28.5; baseline, 161.5 mg/dL; 12 months, 136.4 mg/dL; P < .001 for comparison of all 4 groups). Only patients in the shared physician-patient incentives group achieved reductions in LDL-C levels statistically different from those in the control group (8.5 mg/dL; 95% CI, 3.8-13.3; P = .002). CONCLUSIONS AND RELEVANCE: In primary care practices, shared financial incentives for physicians and patients, but not incentives to physicians or patients alone, resulted in a statistically significant difference in reduction of LDL-C levels at 12 months. This reduction was modest, however, and further information is needed to understand whether this approach represents good value. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01346189. PMID- 26547465 TI - Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication: A Randomized Clinical Trial. AB - IMPORTANCE: Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available. OBJECTIVE: To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle. INTERVENTIONS: A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106). MAIN OUTCOMES AND MEASURES: The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation]). RESULTS: Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions. CONCLUSIONS AND RELEVANCE: Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only. TRIAL REGISTRATION: Netherlands Trial Registry Identifier: NTR2249. PMID- 26547467 TI - Does This Patient With Chest Pain Have Acute Coronary Syndrome?: The Rational Clinical Examination Systematic Review. AB - IMPORTANCE: About 10% of patients with acute chest pain are ultimately diagnosed with acute coronary syndrome (ACS). Early, accurate estimation of the probability of ACS in these patients using the clinical examination could prevent many hospital admissions among low-risk patients and ensure that high-risk patients are promptly treated. OBJECTIVE: To review systematically the accuracy of the initial history, physical examination, electrocardiogram, and risk scores incorporating these elements with the first cardiac-specific troponin. STUDY SELECTION: MEDLINE and EMBASE were searched (January 1, 1995-July 31, 2015), along with reference lists from retrieved articles, to identify prospective studies of diagnostic test accuracy among patients admitted to the emergency department with symptoms suggesting ACS. DATA EXTRACTION AND SYNTHESIS: We identified 2992 unique articles; 58 met inclusion criteria. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and likelihood ratio (LR) of findings for the diagnosis of ACS. The reference standard for ACS was either a final hospital diagnosis of ACS or occurrence of a cardiovascular event within 6 weeks. RESULTS: The clinical findings and risk factors most suggestive of ACS were prior abnormal stress test (specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]), and pain radiation to both arms (specificity, 96%; LR, 2.6 [95% CI, 1.8-3.7]). The most useful electrocardiogram findings were ST-segment depression (specificity, 95%; LR, 5.3 [95% CI, 2.1-8.6]) and any evidence of ischemia (specificity, 91%; LR, 3.6 [95% CI,1.6-5.7]). Both the History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) risk scores performed well in diagnosing ACS: LR, 13 (95% CI, 7.0-24) for the high-risk range of the HEART score (7-10) and LR, 6.8 (95% CI, 5.2-8.9) for the high-risk range of the TIMI score (5-7). The most useful for identifying patients less likely to have ACS were the low-risk range HEART score (0-3) (LR, 0.20 [95% CI, 0.13-0.30]), low risk range TIMI score (0-1) (LR, 0.31 [95% CI, 0.23-0.43]), or low to intermediate risk designation by the Heart Foundation of Australia and Cardiac Society of Australia and New Zealand risk algorithm (LR, 0.24 [95% CI, 0.19 0.31]). CONCLUSIONS AND RELEVANCE: Among patients with suspected ACS presenting to emergency departments, the initial history, physical examination, and electrocardiogram alone did not confirm or exclude the diagnosis of ACS. Instead, the HEART or TIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information. PMID- 26547466 TI - Prevalence and Correlates of Myocardial Scar in a US Cohort. AB - IMPORTANCE: Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population. OBJECTIVE: To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States. DESIGN, SETTING, AND PARTICIPANTS: The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar. EXPOSURES: Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness. MAIN OUTCOMES AND MEASURES: Myocardial scar detected by CMR imaging. RESULTS: Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12 2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P <= .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01). CONCLUSIONS AND RELEVANCE: The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars. PMID- 26547468 TI - Multiple Imputation: A Flexible Tool for Handling Missing Data. PMID- 26547469 TI - Exercise Treadmill Testing. PMID- 26547471 TI - Thrombophilia and the Risk of Recurrent Venous Thromboembolism. PMID- 26547470 TI - Consistency of Laboratory Monitoring During Initiation of Mineralocorticoid Receptor Antagonist Therapy in Patients With Heart Failure. PMID- 26547472 TI - Treatment Trends for Prostate Cancer. PMID- 26547473 TI - Thrombophilia and the Risk of Recurrent Venous Thromboembolism--Reply. PMID- 26547475 TI - Incorrect References and Figure Caption Wording. PMID- 26547474 TI - Treatment Trends for Prostate Cancer--Reply. PMID- 26547477 TI - Angina Pectoris and Arteriosclerosis. PMID- 26547478 TI - JAMA Patient Page. Acute Coronary Syndrome. PMID- 26547479 TI - Leishmaniasis in Yemen: a clinicoepidemiological study of leishmaniasis in central Yemen. AB - BACKGROUND: Leishmaniasis is a serious public health problem in Yemen. OBJECTIVES: This study was designed to identify clinical and epidemiological features of leishmaniasis in Yemen. METHODS: The study was conducted at the Regional Leishmaniasis Control Center in central Yemen. Data sourced from the medical records of 152 patients with confirmed active leishmaniasis, managed during April-August 2013, were analyzed. RESULTS: A total of 94.1% of patients were rural residents. Al Bayda was the most endemic governorate (59.9%). Children represented the group at highest risk (57.2%), followed by adult females (32.9%); together these groups accounted for 90.1% of all patients. Mucocutaneous leishmaniasis was the most prevalent form (49.3%), followed by cutaneous leishmaniasis (47.4%), and visceral leishmaniasis (3.3%). The wet ulcer was the most common type of lesion (49.7%) and the single lesion (69.4%) represented the most common presentation. All patients were ignorant of the nature of the disease, and 55.9% had a history of using "popular" treatments. CONCLUSIONS: Cutaneous, mucocutaneous, and visceral leishmaniases have significant endemicity in Yemen, especially in central areas. Al Bayda is the governorate with the highest endemicity, and rural children and women represent the populations at highest risk. Mucocutaneous leishmaniasis seems to be the most prevalent form and a single wet ulcer is the most common presentation. Infected refugees may represent new foci for imported Leishmania species. Ecology, geography, climate change, cultural gender- and age-specific duties, urban night activities, and use of popular treatments are among proven risk factors. PMID- 26547480 TI - Effect upon mortality of the extension to holidays and weekends of the "ICU without walls" project. A before-after study. AB - OBJECTIVE: To determine whether extension to holidays and weekends of the protocol for the early proactive detection of severity in hospital ("ICU without walls" project) results in decreased mortality among patients admitted to the ICU during those days. DESIGN: A quasi-experimental before-after study was carried out. SETTING: A level 2 hospital with 210 beds and a polyvalent ICU with 8 beds. PATIENTS OR PARTICIPANTS: The control group involved no "ICU without walls" activity on holidays or weekends and included those patients admitted to the ICU on those days between 1 January 2010 and 30 April 2013. The intervention group in turn extended the "ICU without walls" activity to holidays and weekends, and included those patients admitted on those days between 1 May 2013 and 31 October 2014. Patients arriving from the operating room after scheduled surgery were excluded. VARIABLES OF INTEREST: An analysis was made of the demographic variables (age, gender), origin (emergency room, hospital ward, operating room), type of patient (medical, surgical), reason for admission, comorbidities and SAPS 3 score as a measure of severity upon admission, stay in the ICU and in hospital, and mortality in the ICU and in hospital. RESULTS: A total of 389 and 161 patients were included in the control group and intervention group, respectively. There were no differences between the 2 groups except as regards cardiovascular comorbidity (49% in the control group versus 33% in the intervention group; P<.001), severity upon admission (median SAPS 3 score 52 [percentiles 25-75: 42 63) in the control group versus 48 [percentiles 25-75: 40-56] in the intervention group; P=.008) and mortality in the ICU (11% in the control group [95% CI 8-14] versus 3% [95% CI 1-7] in the intervention group; P=.003). In the multivariate analysis, the only 2 factors associated to mortality in the ICU were the SAPS 3 score (OR 1.08; 95% CI 1.06-1.11) and inclusion in the intervention group (OR 0.33; 95% CI 0.12-0.89). CONCLUSIONS: Extension of the "ICU without walls" activity to holidays and weekends results in a decrease in mortality in the ICU. PMID- 26547481 TI - Ambulatory proctologic surgery: Recommendations of the French National Coloproctology Society (SNFCP). PMID- 26547482 TI - Parents' Perspectives on Shared Decision Making for Children With Solid Organ Transplants. AB - INTRODUCTION: The Institute of Medicine prioritizes active family and clinician participation in treatment decisions, known as shared decision making (SDM). In this article we report the decision-making experiences for parents of children who had a solid organ transplant. METHOD: We performed a prospective longitudinal mixed methods study at five major U.S. children's medical centers. Qualitative interview data were obtained at 3 weeks, 3 months, and 6 months after hospital discharge following the child's transplant. RESULTS: Forty-eight parents participated in the study. Three themes were identified: (a) Parents expect to participate in SDM; (b) parents seek information to support their participation in SDM; and (c) attributes of providers' professional practice facilitates SDM. SDM was facilitated when providers were knowledgeable, transparent, approachable, accessible, dependable, and supportive. CONCLUSIONS: Parents expect to participate in SDM with their transplant team. Health care providers can intentionally use the six key attributes to engage parents in SDM. The results provide a framework to consider enhancing SDM in other chronic illness populations. PMID- 26547483 TI - A Retrospective Administrative Claims Database Evaluation of the Utilization of Belimumab in US Managed Care Settings. AB - PURPOSE: Belimumab is an approved therapy for the treatment of systemic lupus erythematosus (SLE). This study examined the real-world utilization patterns of belimumab and standard SLE therapies in patients after regulatory approval of belimumab in the United States. METHODS: A retrospective, observational study of belimumab users in the HealthCore Integrated Research Database was conducted using administrative claims data (GlaxoSmithKline Clinical Study Register Study ID: 114955). The overall population for analysis was composed of patients who were prescribed belimumab, had >=6 months pre- and >=6 months post-index medical and pharmacy eligibility, and at least 1 medical claim for SLE. Patients' clinical and demographic characteristics, treatment history, treatment patterns of belimumab, utilization of other medications, all-cause resource utilization, and costs were assessed. No hypotheses were tested. FINDINGS: All patients who were prescribed belimumab had an SLE claim. Patients who met all eligibility criteria (n = 155) were primarily female (94.2%; mean [SD] age, 44 [12] years) and 94.2% had used standard SLE therapies during the pre- and post-index periods. The majority had moderate SLE disease severity pre-index, and there was a small shift (approximately 8%) from moderate to mild SLE after initiation of belimumab. Two thirds of patients remained on belimumab therapy at 6 months post-index. The percentage of patients with any claim for oral corticosteroids remained stable; however, the point estimate for mean daily dose decreased slightly in months 3 to 6 post-index. Inpatient hospital admissions decreased slightly in the post-index period. The point estimate for total costs (excluding belimumab) decreased after initiation of belimumab, although overall total health care costs (including belimumab) increased. IMPLICATIONS: All patients with a belimumab prescription had an SLE diagnosis on at least 1 medical claim, and the vast majority of those meeting all eligibility criteria had previously used a standard SLE therapy. Disease severity improved for a number of patients while on belimumab treatment and modest corticosteroid dose reductions were observed in later months. After initiating belimumab, health care costs (excluding belimumab) decreased. GlaxoSmithKline Clinical Study Register Study ID: 114955. PMID- 26547484 TI - The relationship among gastroparetic symptoms, quality of life, and gastric emptying in patients referred for gastric emptying testing. AB - BACKGROUND: Symptoms suggestive of gastroparesis are non-specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying. METHODS: Gastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates. KEY RESULTS: Two hundred and sixty-six patients participated (195 females; mean age, 49.1 +/- 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity. CONCLUSIONS & INFERENCES: In patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying. PMID- 26547485 TI - Pericardial and myocardial disease. PMID- 26547486 TI - The 2015 ESC Guidelines on the diagnosis and management of pericardial diseases. PMID- 26547487 TI - A comparison of hysterosalpingo-foam sonography (HyFoSy) and hysterosalpingo contrast sonography with saline medium (HyCoSy) in the assessment of tubal patency. AB - OBJECTIVE: A randomized controlled selective cross-over trial was performed to compare the diagnostic yield and efficacy of ExEm foam (HyFoSy) with saline medium (HyCoSy) as a contrast agent for hysterosalping-contrast sonography in subfertile patients. STUDY DESIGN: 40 patients were randomized into HyCoSy with saline medium and HyFoSy with ExEm foam. Tubal patency were assessed according to pre-determined objective criteria that classified tubes based on degree of certainty in tubal patency. Selective cross-over testing with the other medium was performed in patients who had at least one possibly occluded or unexaminable tube on the initial test. RESULTS: 80 tubes were evaluated. On initial testing, the proportion of tubes that were classified as patent was higher with HyFoSy compared to HyCoSy (70.0% vs 40.0%, p=0.01). A higher proportion of patients in the HyCoSy group required crossover testing [80.0% (16/20) vs 45.0% (9/20), p=0.02]. On cross-over testing, 41.7% (10/24) of possibly occluded or unexaminable tubes in the HyCoSy group were re-classified as patent when examined with Ex-Em foam, compared to 8.3% (1/12) of possibly occluded or unexaminable tubes in the HyFoSy group (p=0.03). CONCLUSION: ExEm foam medium (HyFoSy) might improve the diagnostic yield and efficacy over saline medium (HyCoSy) for hysterosalpingsonography. PMID- 26547488 TI - Colo-uterine fistula due to colonic diverticulitis. Incidental radiological finding. PMID- 26547490 TI - Regularized MANOVA (rMANOVA) in untargeted metabolomics. AB - Many advanced metabolomics experiments currently lead to data where a large number of response variables were measured while one or several factors were changed. Often the number of response variables vastly exceeds the sample size and well-established techniques such as multivariate analysis of variance (MANOVA) cannot be used to analyze the data. ANOVA simultaneous component analysis (ASCA) is an alternative to MANOVA for analysis of metabolomics data from an experimental design. In this paper, we show that ASCA assumes that none of the metabolites are correlated and that they all have the same variance. Because of these assumptions, ASCA may relate the wrong variables to a factor. This reduces the power of the method and hampers interpretation. We propose an improved model that is essentially a weighted average of the ASCA and MANOVA models. The optimal weight is determined in a data-driven fashion. Compared to ASCA, this method assumes that variables can correlate, leading to a more realistic view of the data. Compared to MANOVA, the model is also applicable when the number of samples is (much) smaller than the number of variables. These advantages are demonstrated by means of simulated and real data examples. The source code of the method is available from the first author upon request, and at the following github repository: https://github.com/JasperE/regularized-MANOVA. PMID- 26547491 TI - Review of recent developments and applications in low-pressure (vacuum outlet) gas chromatography. AB - The concept of low pressure (LP) vacuum outlet gas chromatography (GC) was introduced more than 50 years ago, but it was not until the 2000s that its theoretical applicability to fast analysis of GC-amenable chemicals was realized. In practice, LPGC is implemented by placing the outlet of a short, wide (typically 10-15 m, 0.53 mm inner diameter) analytical column under vacuum conditions, which speeds the separation by reducing viscosity of the carrier gas, thereby leading to a higher optimal flow rate for the most separation efficiency. To keep the inlet at normal operating pressures, the analytical column is commonly coupled to a short, narrow uncoated restriction capillary that also acts as a guard column. The faster separations in LPGC usually result in worse separation efficiency relative to conventional GC, but selective detection usually overcomes this drawback. Mass spectrometry (MS) provides highly selective and sensitive universal detection, and nearly all GC-MS instruments provide vacuum outlet conditions for implementation of LPGC-MS(/MS) without need for adaptations. In addition to higher sample throughput, LPGC provides other benefits, including lower detection limits, less chance of analyte degradation, reduced peak tailing, increased sample loadability, and more ruggedness without overly narrow peaks that would necessitate excessively fast data acquisition rates. This critical review summarizes recent developments in the application of LPGC with MS and other detectors in the analysis of pesticides, environmental contaminants, explosives, phytosterols, and other semi-volatile compounds. PMID- 26547489 TI - Domestic exposure to endotoxin and respiratory morbidity in former smokers with COPD. AB - Indoor air pollution has been linked to adverse chronic obstructive pulmonary disease (COPD) health, but specific causative agents have not yet been identified. We evaluated the role of indoor endotoxin exposure upon respiratory health in former smokers with COPD. Eighty-four adults with moderate to severe COPD were followed longitudinally and indoor air and dust samples collected at baseline, 3 and 6 months. Respiratory outcomes were repeatedly assessed at each time point. The associations between endotoxin exposure in air and settled dust and health outcomes were explored using generalizing estimating equations in multivariate models accounting for confounders. Dust endotoxin concentrations in the main living area were highest in spring and lowest in fall, while airborne endotoxins remained steady across seasons. Airborne and dust endotoxin concentrations were weakly correlated with one another (rs = +0.24, P = 0.005). Endotoxin concentrations were not significantly associated with respiratory symptoms, rescue medication use, quality of life, or severe exacerbations. In vitro whole-blood assays of the pro-inflammatory capacity of PM10 filters with and without endotoxin depletion demonstrated that the endotoxin component of indoor air pollution was not the primary trigger for interleukin-1beta release. Our findings support that endotoxin is not the major driver in the adverse effects of indoor PM upon COPD morbidity. PMID- 26547492 TI - Recent developments in computer vision-based analytical chemistry: A tutorial review. AB - Chemical analysis based on colour changes recorded with imaging devices is gaining increasing interest. This is due to its several significant advantages, such as simplicity of use, and the fact that it is easily combinable with portable and widely distributed imaging devices, resulting in friendly analytical procedures in many areas that demand out-of-lab applications for in situ and real time monitoring. This tutorial review covers computer vision-based analytical (CVAC) procedures and systems from 2005 to 2015, a period of time when 87.5% of the papers on this topic were published. The background regarding colour spaces and recent analytical system architectures of interest in analytical chemistry is presented in the form of a tutorial. Moreover, issues regarding images, such as the influence of illuminants, and the most relevant techniques for processing and analysing digital images are addressed. Some of the most relevant applications are then detailed, highlighting their main characteristics. Finally, our opinion about future perspectives is discussed. PMID- 26547493 TI - The Cu-MOF-199/single-walled carbon nanotubes modified electrode for simultaneous determination of hydroquinone and catechol with extended linear ranges and lower detection limits. AB - A novel electrochemical sensor based on Cu-MOF-199 [Cu-MOF-199 = Cu3(BTC)2 (BTC = 1,3,5-benzenetricarboxylicacid)] and SWCNTs (single-walled carbon nanotubes) was fabricated for the simultaneous determination of hydroquinone (HQ) and catechol (CT). The modification procedure was carried out through casting SWCNTs on the bare glassy carbon electrode (GCE) and followed by the electrodeposition of Cu MOF-199 on the SWCNTs modified electrode. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) were performed to characterize the electrochemical performance and surface characteristics of the as-prepared sensor. The composite electrode exhibited an excellent electrocatalytic activity with increased electrochemical signals towards the oxidation of HQ and CT, owing to the synergistic effect of SWCNTs and Cu-MOF-199. Under the optimized condition, the linear response range were from 0.1 to 1453 MUmol L(-1) (RHQ = 0.9999) for HQ and 0.1-1150 MUmol L(-1) (RCT = 0.9990) for CT. The detection limits for HQ and CT were as low as 0.08 and 0.1 MUmol L(-1), respectively. Moreover, the modified electrode presented the good reproducibility and the excellent anti-interference performance. The analytical performance of the developed sensor for the simultaneous detection of HQ and CT had been evaluated in practical samples with satisfying results. PMID- 26547494 TI - Highly selective and sensitive simple sensor based on electrochemically treated nano polypyrrole-sodium dodecyl sulphate film for the detection of para nitrophenol. AB - An ultrasensitive and highly selective electrochemical sensor for the determination of p-nitrophenol (p-NP) was developed based on electrochemically treated nano polypyrrole/sodium dodecyl sulphate film (ENPPy/SDS film) modified glassy carbon electrode. The nano polypyrrole/sodium dodecyl sulphate film (NPPy/SDS film) was prepared and treated electrochemically in phosphate buffer solution. The surface morphology and elemental analysis of treated and untreated NPPy/SDS film were characterized by FESEM and EDX analysis, respectively. Wettability of polymer films were analysed by contact angle test. The hydrophilic nature of the polymer film decreased after electrochemical treatment. Effect of the pH of electrolyte and thickness of the ENPPy/SDS film on determination of p NP was optimised by cyclic voltammetry. Under the optimised conditions, the p-NP was determined from the oxidation peak of p-hydroxyaminophenol which was formed from the reduction of p-NP in the reduction segment of cyclic voltammetry. A very good linear detection range (from 0.1 nM to 100 MUM) and the best LOD (0.1 nM) were obtained for p-NP with very good selectivity. This detection limit is below to the allowed limit in drinking water, 0.43 MUM, proposed by the U.S. Environmental Protection Agency (EPA) and earlier reports. Moreover, ENPPy/SDS film based sensor exhibits high sensitivity (4.4546 MUA MUM(-1)) to p-NP. Experimental results show that it is a fast and simple sensor for p-NP. PMID- 26547495 TI - Extraction of trace nitrophenols in environmental water samples using boronate affinity sorbent. AB - In this research, the applicability of a new sorbent based on boronate affinity material is demonstrated. For this purpose, six strong polar nitrophenols were selected as models which are difficult to be extracted in neutral form (only based on hydrophobic interactions). The extracted nitrophenols were separated and determined by high-performance liquid chromatography with diode array detection. The sorbent was synthesized by in situ copolymerization of 3 acrylamidophenylboronic acid and divinylbenzene using dimethyl sulfoxide and azobisisobutyronitrile as porogen solvent and initiator, respectively. The effect of the preparation parameters in the polymerization mixture on extraction performance was investigated in detail. The size and morphology of the sorbent have been characterized via different techniques such as infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The important parameters influencing the extraction efficiency were studied and optimized thoroughly. Under the optimum extraction conditions, the limits of detection (S/N = 3) and limits of quantification (S/N = 10) for the target nitrophenols were 0.097-0.28 and 0.32-0.92 MUg/L, respectively. The precision of the proposed method was evaluated in terms of intra- and inter-assay variability calculated as RSD, and it was found that the RSDs were all below 9%. Finally, the developed method was successfully applied for environmental water samples such as wastewater, tap, lake and river water. The recoveries varied within the range of 71.2-115% with RSD below 11% in all cases. The results well demonstrate that the new boronate affinity sorbent can extract nitrophenols effectively through multi-interactions including boron-nitrogen coordination, hydrogen-bond and hydrophobic interactions between sorbent and analytes. PMID- 26547496 TI - Label-free aptamer biosensor for selective detection of thrombin. AB - We fabricated a novel fluorescence biosensor for the selective detection of thrombin by using bovine serum albumin-capped CdS quantum dots (BSA-CdS QDs). Two kinds of designed DNA (DNA1 and DNA2) could bind to CdS QDs through the electrostatic interaction between DNA and Cd(2+) on the surface of CdS QDs. The obtained DNA/BSA-CdS QDs kept stable in the solution with the fluorescence intensity obviously enhanced. Hairpin structure of DNA1contained two domains, one is the aptamer sequence of thrombin and the other is the complementary sequence of DNA2. When thrombin was added, it would bind to DNA1 and induce the hairpin structure of DNA1 changed into G-quadplex structure. Meanwhile, DNA2 would transfer from the surface of CdS QDs to DNA1 via hybridization, which resulted in the removal of DNA1 and DNA2 from the surface of CdS QDs, and led to the fluorescence intensity of CdS QDs reduced. Thus, the determination of thrombin could be achieved by monitoring the change of the fluorescence intensity of CdS QDs. The present method is simple and fast, and exhibits good selectivity for thrombin over other proteins. We have successfully detected thrombin in human serum samples with satisfactory results. PMID- 26547497 TI - Sensitive electrochemical immunoassay for chlorpyrifos by using flake-like Fe3O4 modified carbon nanotubes as the enhanced multienzyme label. AB - A highly sensitive electrochemical immunoassay of chlorpyrifos (CPF) was developed by using a biocompatible quinone-rich polydopamine nanospheres modified glass carbon electrode as the sensor platform and multi-horseradish peroxidase flake like Fe3O4 coated carbon nanotube nanocomposites as the signal label. Due to the quinone-rich polydopamine nanospheres, the platform exhibited excellent fixing capacity by simple coating of sticky polydopamine nanospheres and subsequent oxidization. By coprecipitation of Fe(3+) and Fe(2+) on polydopamine modified carbon nanotubes (CNTs) with the aid of ethylene glycol (EG), the flake like Fe3O4 coated CNTs (CNTs@f-Fe3O4) were synthesized and chosen as the carrier of multi-enzyme label due to the high loading of secondary antibody (Ab2) and horseradish peroxidase (HRP) and also the peroxidase-mimic activity of Fe3O4. Under the optimum conditions, the immunosensor can detect CPF over a wide range with a detection limit of 6.3 pg/mL. Besides, the high specificity, reproducibility and stability of the proposed immunosensor were also proved. The preliminary application in real sample showed good recoveries, indicating it holds promise for fast analysis of CPF in aquatic environment. PMID- 26547498 TI - Horseradish peroxidase and aptamer dual-functionalized nanoprobe for the amplification detection of alpha-methylacyl-CoA racemase. AB - Alpha-methylacyl-CoA racemase (AMACR) is over-expressed in many cancer types and can serve as a novel diagnostic biomarker. Development of convenient and sensitive detection methods of AMACR is of particular importance for cancer diagnosis. Aptamers are a type of recognition elements, which possess many advantages over antibody, making them suitable for applications in biosensing and biotechnology. In this work, we use the efficient surface modification of gold nanoparticles (AuNPs) to prepare the horseradish peroxidase (HRP) and aptamer dual-functionalized nanoprobe. The immobilization of HRP and thiol-terminated aptamer on the surface of AuNPs can be achieved through electrostatic interaction and the formation of Au-S bond, respectively. This nanoprobe, which is used as discriminating and catalytic probe, can be combined with enzyme immunoassay method to increase the detection sensitivity of AMACR. The detection limit can reach as low as 4.6 pg mL(-1) due to the dual signal amplification from enzymatic cycling and the high loading of enzymes on AuNPs. This sensitivity is about three orders of magnitude higher than that of AMACR aptamer based fluorescence method, which is also comparable to or one order of magnitude higher than that of ELISA. Furthermore, this method is more simple and effective, which not only avoids the conjugation between recognition element and the catalytic enzyme, but also achieves greater signal amplification. This assay could be used as a sensitive and selective platform for the detection of target protein. PMID- 26547499 TI - Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data. AB - Black patients chronically infected with genotype 1 hepatitis C virus (HCV) have historically had lower rates of response to interferon-based treatment than patients of other races. In the phase 3 ION program, the single-tablet regimen of the NS5A inhibitor ledipasvir and NS5B nucleotide polymerase inhibitor sofosbuvir was shown to be safe and highly effective in the general population. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir in black patients using data from the three open-label ION clinical trials, which evaluated the safety and efficacy of 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin for the treatment of treatment-naive and treatment experienced patients with genotype 1 HCV, including those with compensated cirrhosis. The primary endpoint was sustained virologic response at 12 weeks after the end of therapy (SVR12). For our analysis, rates of SVR12, treatment emergent adverse events, and graded laboratory abnormalities were analyzed in black versus non-black patients. Of the 1949 patients evaluated, 308 (16%) were black. On average, black patients were older, had higher body mass index, were more likely to be IL28B non-CC, and had a lower serum alanine aminotransferase at baseline than non-black patients. Overall, 95% of black and 97% of non-black patients achieved SVR12. The rate of relapse was 3% in black patients as compared with 2% in non-black patients. The most common adverse events included fatigue, headache, nausea, and insomnia. The majority of adverse events occurred more frequently in the ribavirin-containing arms of the studies. No differences were observed in overall safety by race. CONCLUSION: A once-daily dosage of ledipasvir/sofosbuvir was similarly effective in black and non-black patients with genotype 1 HCV infection. The addition of ribavirin did not appear to increase SVR12 but was associated with higher rates of adverse events. PMID- 26547500 TI - Prediction of conformationally dependent atomic multipole moments in carbohydrates. AB - The conformational flexibility of carbohydrates is challenging within the field of computational chemistry. This flexibility causes the electron density to change, which leads to fluctuating atomic multipole moments. Quantum Chemical Topology (QCT) allows for the partitioning of an "atom in a molecule," thus localizing electron density to finite atomic domains, which permits the unambiguous evaluation of atomic multipole moments. By selecting an ensemble of physically realistic conformers of a chemical system, one evaluates the various multipole moments at defined points in configuration space. The subsequent implementation of the machine learning method kriging delivers the evaluation of an analytical function, which smoothly interpolates between these points. This allows for the prediction of atomic multipole moments at new points in conformational space, not trained for but within prediction range. In this work, we demonstrate that the carbohydrates erythrose and threose are amenable to the above methodology. We investigate how kriging models respond when the training ensemble incorporating multiple energy minima and their environment in conformational space. Additionally, we evaluate the gains in predictive capacity of our models as the size of the training ensemble increases. We believe this approach to be entirely novel within the field of carbohydrates. For a modest training set size of 600, more than 90% of the external test configurations have an error in the total (predicted) electrostatic energy (relative to ab initio) of maximum 1 kJ mol(-1) for open chains and just over 90% an error of maximum 4 kJ mol(-1) for rings. PMID- 26547501 TI - A novel mutation, c.494C>A (p.Ala165Asp), in the GPR143 gene causes a mild phenotype in a Chinese X-linked ocular albinism patient. PMID- 26547502 TI - Pretreatment combining ultrasound and sodium percarbonate under mild conditions for efficient degradation of corn stover. AB - Ultrasound (US) can be used to disrupt microcrystalline cellulose to give nanofibers via ultrasonic cavitation. Sodium percarbonate (SP), consisting of sodium carbonate and hydrogen peroxide, generates highly reactive radicals, which cause oxidative delignification. Here, we describe a novel pretreatment technique using a combination of US and SP (US-SP) for the efficient saccharification of cellulose and hemicellulose in lignocellulosic corn stover. Although US-SP pretreatment was conducted under mild condition (i.e., at room temperature and atmospheric pressure), the pretreatment greatly increased lignin removal and cellulose digestibility. We also determined the optimum US-SP treatment conditions, such as ultrasonic power output, pretreatment time, pretreatment temperature, and SP concentration for an efficient cellulose saccharification. Moreover, xylose could be effectively recovered from US-SP pretreated biomass without the formation of microbial inhibitor furfural. PMID- 26547503 TI - A pragmatic and scalable strategy using mobile technology to promote sustained lifestyle changes to prevent type 2 diabetes in India-Outcome of screening. AB - AIMS: We describe a two-step screening approach using non-invasive risk assessment and glycated hemoglobin (HbA1c) to identify participants for a diabetes prevention trial. METHODS: A total of 6030 non-diabetic persons of 35-55 years were screened using risk assessment for diabetes. Those with three or more risk factors were screened using point of care HbA1c test. For this study, participants in HbA1c categories of 6.0% (42.1 mmol/mol)-6.4% (46.4 mmol/mol) were selected and their characteristics were analyzed. RESULTS: Among 6030 persons, 2835 (47%) had three or more risk factors for diabetes. Among those screened with HbA1c, 43.2% (1225) had HbA1c values of <6.0% (42.1 mmol/mol), 46.8% (1327) had HbA1c values between 6.0% (42.1 mmol/mol) and <= 6.4% (46.4 mmol/mol) and 10% (283) had undiagnosed diabetes with >=6.5% (47.5 mmol/mol). Positive family history was present in 53.2%, 81.7% were obese and 14.8% were overweight. CONCLUSIONS: Opportunistic screening using a two-step approach: diabetes risk profile and HbA1c measurement detected a large percentage of individuals with prediabetes. Prediabetic persons recruited to the trial had higher percentage of obesity and presence of positive family history than those who had lower HbA1c values. Outcomes from this trial will enable comparisons with the previous prevention studies that used blood glucose levels as the screening criteria. PMID- 26547504 TI - Helicobacter pylori infection associated with type 2 diabetic nephropathy in patients with dyspeptic symptoms. AB - AIMS: The aim of this conventional case-control study was to investigate the prevalence and relationship between Helicobacter pylori infection in type 2 diabetes mellitus (DM) and diabetic nephropathy (DN). METHODS: A total of 241 type 2 DM patients and 69 non-diabetic subjects with dyspeptic symptoms were enrolled in the study. Gastroduodenal lesions were observed by gastrointestinal endoscopy and the presence of H. pylori was identified by rapid urease test and serum IgG antibodies to H. pylori. According to the urinary albumin excretion rate (UAE), patients were classified into diabetes mellitus group (DM group, with UAE <30 mg/24h); diabetic nephropathy group 1 (DN group 1, with UAE 30 mg/24 h to <300 mg/24 h); and diabetic nephropathy group 2 (DN group 2 >= 300 mg/24 h). The 69 non-diabetic subjects were used as control group. The serum levels of inflammatory factors such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-8 were determined using ELISA. RESULTS: The prevalence of H. pylori infection in DN group 1 and DN group 2 was 45/72 (62.5%) and 34/53 (64.15%), respectively, which was significantly higher than in control [28/65 (43.1%)] and DM groups [42.9% (27/63)]. No significant differences of H. pylori prevalence were detected between DN groups as well as DM and control groups. Interestingly, in both DN groups, higher levels of IL-8, TNF-alpha and urinary albumin excretion rate were found in H. pylori positive subjects. CONCLUSIONS: Diabetic nephropathy patients are more susceptible to H. pylori infection. Our data support an association between H. pylori infection and diabetic nephropathy. PMID- 26547505 TI - Design and control of multi-actuated atomic force microscope for large-range and high-speed imaging. AB - This paper presents the design and control of a high-speed and large-range atomic force microscopy (AFM). A multi-actuation scheme is proposed where several nano positioners cooperate to achieve the range and speed requirements. A simple data based control design methodology is presented to effectively operate the AFM scanner components. The proposed controllers compensate for the coupled dynamics and divide the positioning responsibilities between the scanner components. As a result, the multi-actuated scanner behavior is equivalent to that of a single X-Y Z positioner with large range and high speed. The scanner of the designed AFM is composed of five nano-positioners, features 6 MUm out-of-plane and 120 MUm lateral ranges and is capable of high-speed operation. The presented AFM has a modular design with laser spot size of 3.5 MUm suitable for small cantilever, an optical view of the sample and probe, a conveniently large waterproof sample stage and a 20 MHz data throughput for high resolution image acquisition at high imaging speeds. This AFM is used to visualize etching of calcite in a solution of sulfuric acid. Layer-by-layer dissolution and pit formation along the crystalline lines in a low pH environment is observed in real time. PMID- 26547506 TI - Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis. AB - Primary myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) characterized by megakaryocyte hyperplasia, progressive bone marrow fibrosis, extramedullary hematopoiesis and transformation to Acute Myeloid Leukemia (AML). A number of phenotypic driver (JAK2, CALR, MPL) and additional subclonal mutations have been described in PMF, pointing to a complex genomic landscape. To discover novel genomic lesions that can contribute to disease phenotype and/or development, gene expression and copy number signals were integrated and several genomic abnormalities leading to a concordant alteration in gene expression levels were identified. In particular, copy number gain in the polyamine oxidase (PAOX) gene locus was accompanied by a coordinated transcriptional up-regulation in PMF patients. PAOX inhibition resulted in rapid cell death of PMF progenitor cells, while sparing normal cells, suggesting that PAOX inhibition could represent a therapeutic strategy to selectively target PMF cells without affecting normal hematopoietic cells' survival. Moreover, copy number loss in the chromatin modifier HMGXB4 gene correlates with a concomitant transcriptional down regulation in PMF patients. Interestingly, silencing of HMGXB4 induces megakaryocyte differentiation, while inhibiting erythroid development, in human hematopoietic stem/progenitor cells. These results highlight a previously un reported, yet potentially interesting role of HMGXB4 in the hematopoietic system and suggest that genomic and transcriptional imbalances of HMGXB4 could contribute to the aberrant expansion of the megakaryocytic lineage that characterizes PMF patients. PMID- 26547508 TI - A Patchwork Paper: What Paediatricians Should Read. AB - This paper honours a paediatrician whose career has been patchwork but distinguished, with many facets. It is a light-hearted look at the printed (infinitely preferable to the electronic) word. Although the obvious response is "read everything I have written", this would only drive down the stores of Prozac. Read the scientific literature of course. The oldie reads to stay one jump ahead on the ward round. Meta-analyses and systematic reviews rely on the judgement of others, so should be regarded with suspicion. Do your own research, and do not rely on the thoughts of other people. Read beyond PubMed. "There is more in Heaven and Earth, Horatio, than is dreamed of in your PubMed" (Shakespeare). Read the giants of the past. Richard Asher has so much to teach. What are the seven sins of medicine, and how many have you committed? Asher is top read of the talk. Learn from the mistakes of the past. Your patient comes first. Read how the medical profession covered up the death of Steve Biko and never compromise with patient safety and your integrity. Finally, remember thou art mortal - read a real book for pleasure. Kindle reading must be like making love to an inflatable doll (not that I have done either). Choose what you relax with; for me, PG Wodehouse, Jane Austen, Billy Bunter and Wisden. Who said and why: 'Madam, under similar circumstances I would have kicked the Archangel Gabriel!'. PMID- 26547507 TI - Is ITP a thrombophilic disorder? AB - Immune thrombocytopenia (ITP) represents the epitome of acquired bleeding diseases for the hematologist. Stemming from the interest for the safety of thrombopoietin-receptor agonists (TPO-ra) romiplostim and eltrombopag, recent data have investigated if thrombotic risk is also increased in this disorder. In patients not treated with TPO-ra, a slightly higher risk of venous thrombosis (VTE) is consistently found in ITP, but not to a rate demanding special attention in the generality of cases. No significant increase of arterial thrombosis (AT) is apparent. However, age, splenectomy, and personal risk factors may put some ITP patient to a particularly higher risk of venous and arterial thrombosis (three to four times higher than the average subject). Patients exposed to TPO-ra present indirect evidence of a much higher risk of both AT and VTE. Unfortunately, no matched control population is available and the prospective and registrative nature of these studies may have emphasized the incidence of thrombosis, which was recorded as adverse event. The clinician should be able to individualize the best treatment for the patient, taking also into account the thrombotic risk, limiting active treatment of ITP to those patients really at risk of bleeding. PMID- 26547509 TI - Education, education, education. AB - Patient outcomes can be influenced by one of three main mechanisms: the delivery of optimal clinical care, the conduct of high quality research and through teaching and mentorship of other health care professionals. Measurable educational outcomes include the mentorship of others, the publication of guidelines and the authorship of journal articles. There is good evidence to support an optimal profile for medical educators and evidence that optimal teaching can improve outcomes for children with asthma. The evidence for the value of clinical guidelines and even the publication of research is limited. PMID- 26547510 TI - Origins of multisynaptic projections from the basal ganglia to the forelimb region of the ventral premotor cortex in macaque monkeys. AB - The ventral premotor cortex (PMv), occupying the ventral aspect of area 6 in the frontal lobe, has been implicated in action planning and execution based on visual signals. Although the PMv has been characterized by cortico-cortical connections with specific subregions of the parietal and prefrontal cortical areas, a topographical input/output organization between the PMv and the basal ganglia (BG) still remains elusive. In the present study, retrograde transneuronal labelling with the rabies virus was employed to identify the origins of multisynaptic projections from the BG to the PMv. The virus was injected into the forelimb region of the PMv, identified in the ventral aspect of the genu of the arcuate sulcus, in macaque monkeys. The survival time after the virus injection was set to allow either the second- or third-order neuron labelling across two or three synapses. The second-order neurons were observed in the ventral portion (primary motor territory) and the caudodorsal portion (higher order motor territory) of the internal segment of the globus pallidus. Subsequently, the third-order neurons were distributed in the putamen caudal to the anterior commissure, including both the primary and the higher-order motor territories, and in the ventral striatum (limbic territory). In addition, they were found in the dorsolateral portion (motor territory) and ventromedial portion (limbic territory) of the subthalamic nucleus, and in the external segment of the globus pallidus including both the limbic and motor territories. These findings indicate that the PMv receives diverse signals from the primary motor, higher order motor and limbic territories of the BG. PMID- 26547511 TI - Pain Self-Efficacy and Fear of Movement are Similarly Associated with Pain Intensity and Disability in Italian Patients with Chronic Low Back Pain. AB - The purpose of this study was to investigate cross-sectional associations of pain self-efficacy and fear of movement with pain intensity and disability in Italian patients with chronic low back pain (CLBP). One hundred and three adult outpatients with nonspecific CLBP were included in the study. Socio-demographic and clinical characteristics were assessed, together with Italian versions of self-reported questionnaires to measure the four constructs of interest. Multiple linear regression models were built with psychosocial constructs as main determinants, and pain intensity and disability as outcomes. Potential confounding of socio-demographic and clinical characteristics was assessed. Pain self-efficacy and fear of movement displayed moderate correlations with pain intensity (r = -0.41 and 0.42, respectively) and disability (-0.55 and 0.54). Association models adjusted for pain intensity showed that both pain self efficacy (beta = -0.35, 95% CI = -0.5; -0.2, R2 = 41%) and fear of movement (beta = 0.65, 95% CI = 0.36; 0.93, R2 = 40%) are significantly and strongly associated with disability. Pain self-efficacy was no longer significantly associated with pain intensity when disability was added as a confounder to the model, whereas fear of movement retained its significant association (beta = 0.06, 95% CI = 0.00;0.11, R2 = 30%). No other variables acted as confounders in these associations. Pain self-efficacy and fear of movement are very similarly associated with main outcomes in this sample of Italian patients with CLBP. The results of this study suggest that both psychosocial constructs should be considered in clinical management. Future studies should investigate whether these findings can be replicated in other samples, in longitudinal designs and if other variables not measured in this study confound the associations. PMID- 26547513 TI - Apically extruded debris during root canal preparation using Vortex Blue, K3XF, ProTaper Next and Reciproc instruments. AB - AIM: To assess the amount of debris extruded apically during root canal preparation using various nickel-titanium instrumentation systems. METHODOLOGY: Sixty extracted single-rooted mandibular premolar human teeth were randomly assigned to four groups (n = 15 teeth for each group). The canals were then instrumented with the following instrument systems: Vortex Blue (VB; Dentsply Tulsa Dental, Tulsa, OK, USA), K3XF (SybronEndo, Orange, CA, USA), Reciproc (VDW, Munich, Germany) and ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland). Apically extruded debris during instrumentation was collected into pre-weighed Eppendorf tubes. The Eppendorf tubes were then stored in an incubator at 70 degrees C for 5 days. The weight of the dry extruded debris was established by subtracting the pre-instrumentation and post-instrumentation weight of the Eppendorf tubes for each group. The data were analysed using one way analysis of variance (anova) and Tukey's post hoc tests. RESULTS: Vortex Blue and PTN files were associated with significantly less apically extruded debris than the K3XF and Reciproc files (P < 0.05), but there was no significant difference between the VB and PTN files or between the K3XF and Reciproc files (P > 0.05). CONCLUSIONS: All instruments were associated with apical extrusion of debris. VB and PTN files were associated with less debris extrusion compared to the other systems. PMID- 26547512 TI - Differences in sleep disturbances among offspring of parents with and without bipolar disorder: association with conversion to bipolar disorder. AB - OBJECTIVES: Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non-BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non-BP/OB group. METHODS: Pittsburgh Bipolar Offspring Study youth (ages 6-18 years) and their parents completed assessments every two years pertaining to the child's sleep and circadian phenotypes and current psychopathology. Mixed-effects models examined differences in baseline sleep and circadian variables among the three groups. RESULTS: BP/OB offspring who were in a mood episode differed significantly on sleep parameters from the non-BP/OB and the offspring of controls, such as having inadequate sleep. Mixed logistic regression procedures showed that baseline sleep and circadian variables, such as frequent waking during the night, significantly predicted the development of BP among non-BP/OB over longitudinal follow-up. CONCLUSIONS: While lifetime diagnostic status accounted for differences among the groups in sleep and circadian disturbances, psychopathology explained the differences even further. Additionally, sleep disturbance may be a prognostic indicator of the development of BP in high-risk youth. Future studies are required to further disentangle whether sleep and circadian disruption are state or trait features of BP. PMID- 26547514 TI - Ankaferd blood stopper enhances healing after osseous grafting in patients with intrabony periodontal defects. AB - BACKGROUND AND OBJECTIVE: The aim of this clinical study were to compare the clinical efficacy of ankaferd blood stopper (ABS) when used in combination with autogenous cortical bone graft (ACB) in the treatment of intrabony periodontal defects. MATERIAL AND METHODS: The study was planned as a split-mouth design. Fifteen patients with chronic periodontitis at 30 sites (six men, nine women; 42 +/- 7 years) were included. Treatment sites had probing pocket depths (PPD) of >= 6 mm and osseous defect depths of >= 4 mm as radiographically assessed. Following the initial periodontal therapy, patients were randomly assigned to two treatments in contralateral areas of the dentition: ACB + ABS or ACB alone. At baseline and 6 mo after surgery, clinical parameters of plaque index, gingival index, PPD, clinical attachment level and gingival recession (GR) were recorded. The primary outcome variable was the change in clinical attachment level between baseline and 24 wk after surgery. Gingival crevicular fluid samples were collected immediately before surgery and at 2, 4, 6, 12 and 24 wk after the surgery. Gingival crevicular fluid volume was calculated and vascular endothelial growth factor levels in gingival crevicular fluid were measured. RESULTS: PPD decreased, clinical attachment level improved and gingival index decreased significantly in response to both modes of treatment (p < 0.05). Both treatment modalities resulted in a significant gain in radiographic bone levels compared to baseline (p < 0.05). Intergroup comparisons showed that there was a significantly higher gain in clinical attachment level in the ABS/ACB group compared to ACB group (p < 0.05) with significantly less GR (p < 0.05). Similarly, vascular endothelial growth factor concentration in gingival crevicular fluid was significantly higher in the ABS/ACB group at postoperative weeks 2 and 4 compared to the ACB group (p < 0.01). CONCLUSIONS: The findings suggest that ABS enhances the soft tissue healing during the periodontal defect fill by the ACB by stimulating angiogenesis and vascular endothelial cell function, prevents GR and thereby increases the clinical attachment gain. PMID- 26547515 TI - Influence of the larval phase on connectivity: strong differences in the genetic structure of brooders and broadcasters in the Ophioderma longicauda species complex. AB - Closely related species with divergent life history traits are excellent models to infer the role of such traits in genetic diversity and connectivity. Ophioderma longicauda is a brittle star species complex composed of different genetic clusters, including brooders and broadcasters. These species diverged very recently and some of them are sympatric and ecologically syntopic, making them particularly suitable to study the consequences of their trait differences. At the scale of the geographic distribution of the broadcasters (Mediterranean Sea and northeastern Atlantic), we sequenced the mitochondrial marker COI and genotyped an intron (i51) for 788 individuals. In addition, we sequenced 10 nuclear loci newly developed from transcriptome sequences, for six sympatric populations of brooders and broadcasters from Greece. At the large scale, we found a high genetic structure within the brooders (COI: 0.07 < F(ST) < 0.65) and no polymorphism at the nuclear locus i51. In contrast, the broadcasters displayed lower genetic structure (0 < F(ST) < 0.14) and were polymorphic at locus i51. At the regional scale, the multilocus analysis confirmed the contrasting genetic structure between species, with no structure in the broadcasters (global F(ST) < 0.001) and strong structure in the brooders (global F(ST) = 0.49), and revealed a higher genetic diversity in broadcasters. Our study showed that the lecithotrophic larval stage allows on average a 50-fold increase in migration rates, a 280-fold increase in effective size and a threefold to fourfold increase in genetic diversity. Our work, investigating complementary genetic markers on sympatric and syntopic taxa, highlights the strong impact of the larval phase on connectivity and genetic diversity. PMID- 26547516 TI - Immunomodulation of Lactobacillus reuteri CRL1324 on Group B Streptococcus Vaginal Colonization in a Murine Experimental Model. AB - PROBLEM: Maternal Group B Streptococcus (GBS) colonization is a risk factor for infectious disease in newborns. One promising strategy is the modulation of vaginal defense to increase the host's ability to combat infection. METHOD OF STUDY: The effect of intravaginal (i.va.) Lactobacillus reuteri CRL1324 inoculation on different immune cell populations, cytokines, and immunoglobulin isotypes in a murine model of GBS vaginal colonization was evaluated. RESULTS: Seven i.va. inoculations of L. reuteri CRL1324 previous to GBS challenge showed an immunomodulatory effect on the cells and mediators of innate immunity, decreasing the number of neutrophils induced by the pathogen and increasing the activated macrophage population. Moreover, increases in B lymphocytes and IgA and IgG subclasses were observed in mice inoculated with L. reuteri CRL1324 and then challenged with GBS. CONCLUSION: Lactobacillus reuteri CRL1324 shows a protective effect against GBS colonization that could be mediated by the modulation of the immune response. PMID- 26547517 TI - A menu with prices: Annual per person costs of programs addressing community integration. AB - Information on costs of programs addressing community integration for persons with serious mental illness in the United States, essential for program planning and evaluation, is largely lacking. To address this knowledge gap, community integration programs identified through directories and snowball sampling were sent an online survey addressing program costs and organizational attributes. 64 Responses were received for which annual per person costs (APPC) could be computed. Programs were categorized by type of services provided. Program types differed in median APPCs, though median APPCs identified were consistent with the ranges identified in the limited literature available. Multiple regression was used to identify organizational variables underlying APPCs such as psychosocial rehabilitation program type, provision of EBPs, number of volunteers, and percentage of budget spent on direct care staff, though effects sizes were moderate at best. This study adds tentative prices to the menu of community integration programs, and the implications of these findings for choosing, designing and evaluating programs addressing community integration are discussed. PMID- 26547518 TI - Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients. AB - OBJECTIVE: To investigate the impact of multicomponent, nonpharmacologic interventions (MNI) on perioperative cortisol and melatonin levels, as well as postoperative delirium (PD), in elderly oral cancer patients. METHODS: A total of 160 elderly oral cancer patients who underwent tumor resection surgery and completed our investigation were included in this study. The cancer patients were randomly divided into 2 groups: Group U or Group I. During the perioperative period, Group U received usual care, while Group I received MNI, which is based on usual care and aims to decrease the risk of PD. MNI focused on general geriatric approaches and supportive nursing care. On the day before surgery and the first three postoperative days, nocturnal (20:00-8:00) urine samples were collected. The melatonin sulfate and cortisol levels in the urine samples were determined. Moreover, the RASS (Richmond Agitation Sedation Scale), CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) and QoR40 (40-item quality of recovery score) scores were dynamically monitored. RESULTS: There were no significant differences in the general characteristics between the 2 groups. After surgery, the melatonin sulfate levels in the nocturnal urine of Group I were higher than those in Group U. The cortisol concentrations were lower in Group I compared to those in Group U. Group I achieved better postoperative RASS and QoR40 scores than Group U. Compared to Group U, Group I also experienced less PD (incidence and duration). CONCLUSIONS: MNI ameliorated some postoperative disturbances regarding sleep and stress, decreased the incidence of PD and improved recovery quality. PMID- 26547519 TI - Flexural strength of small connector designs of zirconia-based partial fixed dental prostheses. AB - STATEMENT OF PROBLEM: Partial fixed dental prostheses with a small connector size are required for optimal esthetics and limited interarch space; however, final strength is endangered. PURPOSE: The purpose of this in vitro study was to evaluate the effect of different connector designs on the flexural strength of simulated 3-unit partial fixed dental prostheses made of yttria-stabilized tetragonal zirconia polycrystalline using computer-aided design and computer aided manufacturing technology. MATERIAL AND METHODS: To simulate a 3-unit partial fixed dental prosthesis, 20 rectangular bar-shaped specimens were fabricated with dimensions of 4 +/- 0.05 mm (H) * 4 +/- 0.05 mm (W) * 30 0.5 mm (L). Each bar specimen had 2 constricted parts on both sides, representing the connector and defining a central pontic of 10 +/- 0.10 mm in length. The specimens were divided into 4 groups according to the connector diameter and design, as follows: SR: 2 mm (H) * 3 mm (W) round 0.6 mm radius of curvature; SS: 2 mm (H) * 3 mm (W) sharp 0.1 mm radius of curvature; CR: 3 mm (H) * 3 mm (W) round 0.6 mm radius of curvature; and CS: 3 mm (H) * 3 mm (W) sharp 0.1 mm radius of curvature. An additional 5 specimens were fabricated with no constriction and served as the control group. The specimens were subjected to a 3-point flexural strength test in a universal testing machine with a crosshead speed of 0.5 mm/min until failure. Scanning electron microscopic and photomicrograph images were used to examine the fracture surfaces. Two-way ANOVA and the Tukey-Kramer post hoc test were used to analyze the data (alpha = .05). RESULTS: The mean flexural strength for SR 2 mm (H) * 3 mm (W) round 0.6 mm radius of curvature (583.6 +/- 49.7 MPa) was significantly higher than that of SS, which was 2 mm (H)* 3 mm (W) sharp 0.1 mm radius of curvature (502.8 +/- 23.3 MPa). Similarly, the mean flexural strength for CR was 3 mm (H) * 3 mm (W) round 0.6 mm radius of curvature (682.9 +/- 36.8), which was significantly higher than that of CC, 3 mm (H) * 3 mm (W) sharp 0.1 mm radius of curvature (486.7 +/- 35.6 MPa). CONCLUSIONS: The flexural strength of the yttria-stabilized tetragonal zirconia polycrystalline based ceramics was affected by the connector dimension and design. The 2-round connector design was more able to withstand occlusal forces than the sharp design. The 3-connector design with a minimum cross section of 2 * 3 mm is recommended for anterior fixed dental prostheses, provided it has a round curvature. PMID- 26547520 TI - Dental health professional recommendation and consumer habits in denture cleansing. AB - STATEMENT OF PROBLEM: Regular cleaning of dentures is essential to the oral and general health of denture wearers. Only limited systematic data are available on the recommendations that dental health care professionals (DHCPs) make to patients for denture cleaning. Data on denture wearers' cleaning regimens are also lacking. PURPOSE: The purpose of this study was to provide data on recommendations that DHCPs make to patients for denture cleaning and on the cleaning regimens of denture wearers. MATERIAL AND METHODS: DHCPs (n=613), including dentists and hygienists, were surveyed in developed (Japan, USA, Italy) and developing (Brazil, India) countries. A questionnaire assessing a range of denture cleaning recommendations was used. The questions addressed products, frequency, how to use remedies, the suggested dilution and duration of cleansing treatment, the location of dentures while cleaning, and the reasoning behind the recommendation of particular products or modes of treatment. Denture cleansing methods and the routine of denture wearers in developed and developing countries were also surveyed with a questionnaire (n=2862) and a 1-week diary (n=1462). RESULTS: An average of more than 2 treatments was recommended by DHCPs. Specialist denture cleanser tablets, "regular" toothpaste, mouthwash, soap and water, denture paste, foam or liquid denture cleanser, and dishwashing detergents were most commonly recommended; other product recommendations included baking soda, vinegar, salt water, and bleach. More than 10% of DHCPs made no primary recommendation on cleaning. Denture tablets were more commonly recommended in developed countries, whereas toothpaste was the most common recommendation in developing countries. Denture wearers used products and methods similar to those recommended by DHCPs. Toothpaste, water, and mouthwash were used more frequently than denture tablets. More than 75% of denture wearers reported using denture cleanser tablets for more than 5 minutes, whereas soap and toothpaste were typically used for less than 2 minutes. CONCLUSIONS: DHCP recommendations and denture wearer habits are diverse, with no consensus on the most appropriate denture cleaning methods. This reflects a lack of clear, systematic evidence upon which to base recommendations. PMID- 26547521 TI - Predictive factors for relapse of epileptic spasms after adrenocorticotropic hormone therapy in West syndrome. AB - PURPOSE: To investigate whether serial electroencephalographic (EEG) findings can predict relapse of epileptic spasms after synthetic adrenocorticotropic hormone (ACTH) therapy in patients with West syndrome (WS). SUBJECTS AND METHODS: Thirty nine WS patients (8 cryptogenic and 31 symptomatic) were included in this study. These patients received ACTH therapy for the first time and were regularly followed up for more than three years at our hospital. Sixteen patients (41.0%) showed seizure relapse (relapse group) and 23 patients (59.0%) did not show relapse (non-relapse group). We used survival analysis to investigate the influence of etiology and presence of epileptic discharges after the ACTH therapy on seizure outcome. RESULTS: Immediately after the ACTH therapy, etiology was associated with seizure outcome (p=0.003). In the early stage (1 month after the ACTH therapy), only the presence of epileptic discharges (p=0.001) had a significant association with seizure outcome, regardless of etiology. Because all relapsed patients were in the symptomatic group, we performed the same statistical analysis on symptomatic WS patient data only. We found that the group with no epileptic discharges on EEG showed a significantly higher seizure-free rate than those with epileptic discharges in the early stage (p=0.0091). CONCLUSION: This study demonstrated that serial EEG findings after ACTH therapy are significantly related to relapse of epileptic spasms. PMID- 26547522 TI - The transverse force experienced by the radial head during axial loading of the forearm: A cadaveric study. AB - BACKGROUND: When designing a radial head replacement, the magnitude and direction of forces applied across the proximal radio-ulnar joint (PRUJ) and the radiocapitellar joint must be included. These designs often focus on axial loads transmitted to the radial head by the capitellum; however, the radial head also bears a significant transverse force at the PRUJ. Load transmission by the central band of the interosseous ligament induces a force component in a lateral direction perpendicular to the axis of the limb, which is borne by the articular surfaces of the proximal and distal radio-ulnar joints. The objective of this study is to establish the relationship between distally applied axial forces and proximal transverse reaction forces. METHODS: Five cadaveric, human forearms with intact interosseous membranes were used to measure the magnitude of transversely directed forces experienced by the radial head during axial loading of the forearm at the lunate fossa. A Mark-10 test stand applied a gradual and continuous axial load on the articular surface of the distal radius. A Mark-10 force gauge measured the resultant transverse force experienced by the radial head in the proximal radioulnar joint. Classical mechanics and static force analysis were applied in order to predict lateral force values that would occur when the interosseous ligament is treated as the major load transmitter between the radius and ulna. FINDINGS: Acquired data show that the radial head bears a force in the transverse direction that averages 18% (SD 3.89%) in magnitude of the axial force applied at the wrist. This figure is in close accordance with the predicted value of 22% that was calculated by way of free-body plotting. INTERPRETATION: Physiologic forearm loading results in a clinically significant transverse force component transmitted through the interosseous ligament complex. The existence of transverse forces in the human forearm may explain clinical problems seen after radial head resection and suggest that radial head implants be designed to sustain substantial transverse forces. LEVEL OF EVIDENCE: Basic science study, anatomical. PMID- 26547523 TI - Pediatric decision support using adapted Arden Syntax. AB - BACKGROUND: Pediatric guidelines based care is often overlooked because of the constraints of a typical office visit and the sheer number of guidelines that may exist for a patient's visit. In response to this problem, in 2004 we developed a pediatric computer based clinical decision support system using Arden Syntax medical logic modules (MLM). METHODS: The Child Health Improvement through Computer Automation system (CHICA) screens patient families in the waiting room and alerts the physician in the exam room. Here we describe adaptation of Arden Syntax to support production and consumption of patient specific tailored documents for every clinical encounter in CHICA and describe the experiments that demonstrate the effectiveness of this system. RESULTS: As of this writing CHICA has served over 44,000 patients at 7 pediatric clinics in our healthcare system in the last decade and its MLMs have been fired 6182,700 times in "produce" and 5334,021 times in "consume" mode. It has run continuously for over 10 years and has been used by 755 physicians, residents, fellows, nurse practitioners, nurses and clinical staff. There are 429 MLMs implemented in CHICA, using the Arden Syntax standard. Studies of CHICA's effectiveness include several published randomized controlled trials. CONCLUSIONS: Our results show that the Arden Syntax standard provided us with an effective way to represent pediatric guidelines for use in routine care. We only required minor modifications to the standard to support our clinical workflow. Additionally, Arden Syntax implementation in CHICA facilitated the study of many pediatric guidelines in real clinical environments. PMID- 26547524 TI - [Characteristics and management of ST-elevation myocardial infarction in France: Regional variations in 2010]. AB - Data on regional variations in the characteristics, management and early outcome of patients admitted with ST-elevation myocardial infarction (STEMI) in France are limited. We used data from the FAST-MI 2010 registry to determine whether regional specificities existed, dividing the French territory into 6 larger geographical regions. Variations in the patients' characteristics were found, partly related to regional variations in demography. Acute reperfusion strategy showed more use of primary percutaneous coronary intervention in the greater Paris area, compared to other regions, which would be expected owing to geography and local availability of catheterization laboratories. Overall, however, in hospital management showed more similarities than differences across regions. Complications, and in particular in-hospital mortality, did not differ significantly among regions. PMID- 26547525 TI - [Management of patients treated for acute ST-elevation myocardial infarction in Tunisia: Preliminary results of FAST-MI Tunisia Registry from Tunisian Society of Cardiology and Cardiovascular Surgery]. AB - FAST-MI Tunisian registry was initiated by the Tunisian Society of Cardiology and Cardio-vascular Surgery to assess characteristics, management, and hospital outcomes in patients with ST-elevation myocardial infarction (STEMI). METHODS: We prospectively collected data from 203 consecutive patients (mean age 60.3 years, 79.8 % male) with STEMI who were treated in 15 public hospitals (representing 68.2 % of Tunisian public centres treating STEMI patients) during a 3-month period at the end of 2014. The most common risk factor was tobacco (64.9 %), hypertension (38.6 %), diabetes (36.9 %) and dyslipidemia (24.6 %). RESULTS: Among these patients, 66 % received reperfusion therapy, 35 % with primary percutaneous coronary interventions (PAMI), 31 % with thrombolysis (28.6 % of them by pre-hospital thrombolysis). The median time from symptom onset to thrombolysis was 185 and 358 min for PAMI, respectively. The in-hospital mortality was 7.0 %. Patients enrolled in interventional centers (n=156) were more likely to receive any reperfusion therapy (19.8 % vs 44.6 %; p<0.001) than at the regional system of care with less thrombolysis (26.9 % vs 44.6 %; p=0.008) and more PAMI (52.8 % vs 8.5 %; p<0.0001). Also the in-hospital mortality was lower (6.4 % vs 9.3 %) but not significant. CONCLUSIONS: Preliminary results from FAST-MI in Tunisia show that the pharmaco- invasive strategy should be promoted in non-interventional centers. PMID- 26547526 TI - Complications after surgery for metastatic humeral lesions. AB - BACKGROUND: Knowledge of surgical outcome and its predictors helps inform patients and aids in surgical decision-making. We aimed to assess the outcome reoperation and systemic complication rate-of surgery for humeral metastases, myeloma, or lymphoma. Our null hypothesis was that there are no factors associated with these outcomes. METHODS: We included 295 consecutive patients in this retrospective study: 134 (45%) proximal, 131 (44%) diaphyseal, and 30 (10%) distal impending or pathologic fractures. Proximal lesions were treated by intramedullary nailing (43%, n = 57), prosthesis (34%, n = 46), plate-screw fixation (22%, n = 30), and a combination (n = 1). Diaphyseal lesions were treated by intramedullary nailing (69%, n = 91), plate-screw fixation (30%, n = 39), and a combination (n = 1). Distal lesions were treated by plate-screw fixation (97%, n = 29) and intramedullary nailing (3.3%, n = 1). RESULTS: We found 25 (8.5%) reoperations, and 17 (5.8%) patients had 18 systemic complications: pneumonia (3.7%, n = 11), pulmonary embolism (1.3%, n = 4), sepsis (0.68%, n = 2), and fat embolism (0.34%, n = 1). No factors were independently associated with reoperation. Logistic regression analysis demonstrated that favorable cancer status (i.e., a higher modified Bauer score: odds ratio, 0.48; 95% confidence interval, 0.29-0.80; P = .005) was independently associated with a decreased systemic complication rate. CONCLUSION: Poor cancer status was an independent predictor of postoperative systemic complications. This could help inform the patient and anticipate postoperative problems. PMID- 26547527 TI - Editorial overview: Biophysical and molecular biological methods: Structure, dynamics, and single molecules. PMID- 26547528 TI - Extracts from peppermint leaves, lemon balm leaves and in particular angelica roots mimic the pro-secretory action of the herbal preparation STW 5 in the human intestine. AB - AIM: The herbal preparation STW 5 contains fresh plant extracts from bitter candytuft whole plant, extracts from greater celandine herb, angelica root, lemon balm leaves, peppermint leaves, caraway fruit, liquorice root, chamomile flower and milk thistle fruit. We recently reported that STW 5 increased intestinal chloride secretion and proposed that this action may be involved in its clinical efficacy in the treatment of irritable bowel syndrome. The aim of this study was to identify the extracts responsible for the secretory action in order to provide the basis to develop novel target oriented herbal combinations. METHODS: We used the Ussing chamber voltage clamp technique to study the effects of individual extracts of STW 5 on short circuit current (Isc, reflecting electrogenic ion transport across epithelial cells) in mucosal/submucosal preparations of human small or large intestinal specimens and the human epithelial cell line T84. RESULTS: STW 5 at concentrations of 512 ug/ml and 5120 ug/ml evoked an increase in Isc. The increase at the lower concentration was due to pro-secretory effects of angelica which were nerve mediated. The increase at the higher concentration was additionally mimicked by peppermint and lemon balm. The remaining extracts did not influence ISC in the large intestine. The results were similar in T84 cells except that angelica had no effect while chamomile induced secretion. These pro-secretory effects were reduced by adenylate cyclase inhibitor MDL-12330A, cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172 and calcium activated chloride channels blocker 4-acetamido-4 isothiocyanatostilbene-2,2-disulphonic acid (SITS). Liquorice decreased ISC only in small intestine which was reversed by the epithelial sodium channel blocker amiloride. CONCLUSIONS: Results suggested that the pro-secretory action of STW 5 is mainly due to angelica with lesser contribution of peppermint and lemon balm. Their effects involve activation of cAMP- and Ca(++)-activated Cl(-) channels. We suggest that peppermint, lemon balm and in particular angelica may be the basis to develop novel herbal preparations to specifically treat secretory disorder based on impaired epithelial secretion, such as constipation. PMID- 26547529 TI - Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy. AB - BACKGROUND: Recently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis. STUDY DESIGN: We investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50 mg/kg/d), intermediate dose of GbE (100 mg/kg/d), high dose of GbE (200 mg/kg/d) and rapamycin (1 mg/kg/d). METHODS: After 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, alpha-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting. RESULTS: Compared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E cadherin, alpha-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex. CONCLUSION: GbE can prevent renal fibrosis in rats with diabetic nephropathy, which is most likely to be associated with its abilities to inhibit the Akt/mTOR signaling pathway. PMID- 26547530 TI - Dihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer. AB - BACKGROUND: Dihydrotanshinone I (DHTS) was previously reported to exhibit the most potent anti-cancer activity among several tanshinones in colon cancer cells. Its cytotoxic action was reactive oxygen species (ROS) dependent but p53 independent. PURPOSE: To further study the anti-cancer activity of DHTS and its molecular mechanisms of action in colon cancer both in vitro and in vivo. METHODS: Caspase activity was detected by fluorescence assay. Apoptosis was detected by flow cytometry and TUNEL assay. Protein levels were analyzed by western blotting. Knockdown of target gene was achieved by siRNA transfection. Formation of LC3B puncta and activation of caspase-3 were detected by confocal fluorescence microscope. In vivo anti-colon cancer activity of DHTS was observed in xenograft tumors in NOD/SCID mice. RESULTS: Anti-colon cancer activity of DHTS by inducing apoptosis and autophagy was observed both in vitro and in vivo. Mitochondria mediated caspase dependent pathway was essential in DHTS-induced cytotoxicity. The apoptosis induced by DHTS was suppressed by knockdown of apoptosis inducing factor (AIF), inhibition of caspase-3/9 but was increased after knockdown of caspase-2. Meantime, knockdown of caspase-2, pretreatment with Z-VAD-fmk or NAC (N-Acety-L-Cysteine) efficiently inhibited the autophagy induced by DHTS. A crosstalk between cytochrome c and AIF was also reported. CONCLUSION: DHTS-induced caspase and ROS dependent apoptosis and autophagy were mediated by mitochondria in colon cancer. DHTS could be a promising leading compound for the development of anti-tumor agent or be developed as an adjuvant drug for colon cancer therapy. PMID- 26547531 TI - Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (+/-)-vasicine, deoxyvasicine, and (+/-)-vasicinone from aerial parts of Peganum harmala L. AB - BACKGROUND: The aerial parts of Peganum harmala L. (APP) is a well-known and effective herbal medicine in China, and has been commonly used for treating various ailments, including cough and asthma. OBJECTIVES: To evaluate the antitussive, expectorant, and bronchodilating effects of the quinazoline alkaloids (+/-)-vasicine (VAS), deoxyvasicine (DVAS) (both isolated from the alkaloid fraction of APP) and (+/-)-vasicinone (VAO) (synthesized from VAS). METHODS: The three quinazoline alkaloids were tested as antitussive on cough models in mice and guinea pigs. VAO was synthesized from VAS via the oxidation of hydrogen peroxide. VAS, VAO, and DVAS were orally administered at dosages of 5, 15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated by using a bronchoconstrictive induced by acetylcholine chloride and histamine in guinea pigs. RESULTS: In antitussive tests, VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals. At the highest doses tested (45 mg/kg), they showed antitussive activities similar to codeine phosphate (30 mg/kg) in mice and guinea pigs. Expectorant evaluation showed that VAS, VAO, and DVAS could significantly increase phenol red secretion in mice by 0.54-, 0.79- and 0.97-fold, by 0.60-, 0.99-, and 1.06-fold, and by 0.46-, 0.73-, and 0.96-fold, respectively, at dosages of 5, 15, and 45 mg/kg compared with the control (0.5% CMC-Na, 20 ml/kg). Ammonium chloride at 1500 mg/kg increased phenol red secretion in mice by 0.97-fold compared with the control. Bronchodilation tests showed that VAS, VAO, and DVAS prolonged the pre convulsive time for 28.59%, 57.21%, and 29.66%, respectively, at a dose of 45 mg/kg in guinea pigs, whereas aminophylline prolonged the pre-convulsive time by 46.98% compared with pretreatment. CONCLUSIONS: Quinazoline alkaloids VAS, VAO, and DVAS have significant antitussive, expectorant, and bronchodilating activities. VAS, VAO, and DVAS are the active ingredients in APP, which can be used to treat respiratory disease. PMID- 26547532 TI - Cytotoxicity of three naturally occurring flavonoid derived compounds (artocarpesin, cycloartocarpesin and isobavachalcone) towards multi-factorial drug-resistant cancer cells. AB - INTRODUCTION: Cancer remains an aggressive deadly disease, if drug resistance develops. This problem is aggravated by the fact that multiple rather than single mechanisms are involved in resistance and that multidrug resistance (MDR) phenomena cause inefficacy of many clinical established anticancer drugs. We are seeking for novel cytotoxic phytochemicals to combat drug-resistant tumour cells. METHODS: In the present study, we investigated the cytotoxicity of three naturally occurring flavonoids including two flavones artocarpesin (1) and cycloartocarpesin (2) and one chalcone, isobavachalcone (3) against 9 drug sensitive and MDR cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry. RESULTS: Flavones 1 and 2 as well as chalcone 3 displayed cytotoxic effects at various extent on all the 9 tested cancer cell lines with IC50 values respectively below 106 uM, 50 uM and 25 uM. The IC50 values for the three investigational flavonoids ranged from 23.95 uM (towards hepatocarcinoma HepG2 cells) to 105 uM [towards colon carcinoma HCT116 (p53(-/-)) cells] for 1, from 15.51 uM (towards leukemia CCRF-CEM cells) to 49.83 uM [towards glioblastoma U87MG.DeltaEGFR cells] for 2 and from 2.30 uM (towards CCRF-CEM cells) to 23.80 uM [towards colon carcinoma HCT116 (p53(+/+)) cells] for 3 and from 0.20 uM (towards CCRF-CEM cells) to 195.12 uM (towards leukemia CEM/ADR5000 cells) for doxorubicin. Compounds 2 and 3 induced apoptosis in CCRF-CEM leukemia cells, mediated by caspase activation and the disruption of MMP. CONCLUSIONS: The three tested flavonoids and mostly chalcone 3 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. PMID- 26547533 TI - Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells. AB - BACKGROUND: Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation. PURPOSE: The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire(r) 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549. STUDY DESIGN: 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch. METHODS: CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats. RESULTS: The average size of CUR-MM was found to be around 188 +/- 3 nm with an EE of about 76.45 +/- 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55 folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44. CONCLUSION: Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability. PMID- 26547534 TI - Cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. AB - BACKGROUND: Whether sulfated saponins from Holothuria moebii inhibit the proliferation of colorectal cancer cells and have anti-colorectal tumor effects in animal model has not been investigated. PURPOSE: To evaluate the cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. METHOD: (1) Column chromatography was used to prepare the total and individual saponins and HPLC was applied to define the components of the total saponins; (2) the activity of the total and individual saponins inhibiting the proliferation of human colorectal cancer cells was determined by SRB assay and the apoptosis induced by the saponins was qualified using cytometric analysis with Annexin V-FITC/PI double staining; and (3) the antitumor effects of the sulfated saponins on colorectal CT-26 tumor-bearing Balb/c mice were tested. RESULTS: The total and individual sulfated saponins significantly inhibited the proliferation of four different human colorectal cancer cells with IC50 values ranging from 1.04 to 4.08 MUM (or 1.46 to 3.24 MUg/ml for total saponins) and induced late apoptosis at an early treatment time in cancer cells. The total saponins (120 mg/kg) had antitumor activity in colorectal CT-26 tumor-bearing Balb/c mice. CONCLUSION: The sulfated saponins from H. moebii remarkably inhibited the proliferation of different human colorectal cancer cells and had significant anti-colorectal tumor activity in animal model. PMID- 26547535 TI - Citrus limonoid nomilin inhibits osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways. AB - BACKGROUND: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear. PURPOSE: To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts. STUDY DESIGN: Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures. METHODS: Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot. RESULTS: Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways. CONCLUSION: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases. PMID- 26547536 TI - Analgesic effect of total flavonoids from Sanguis draxonis on spared nerve injury rat model of neuropathic pain. AB - BACKGROUND: Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (D. cochinchinensis). The active components of total flavonoids from SD (SDF) have analgesic effect. AIM: The aim of this study is to evaluate the analgesic effects and potential mechanism of SDF on mechanical hypersensitivity induced by spared nerve injury (SNI) model of neuropathic pain in the rat. METHODS: SNI model in rats was established and then the rats were treated with SDF intragastric administration for 14 days. Paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and days 1, 3, 5, 7, 9, 11, 14 after operation, respectively. After 14 days, we measured the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-10) in the spinal dorsal horn. In addition, the expression of fibroblast growth factor receptor 3 (FGFR3), phosphorylated cyclic AMP response element-binding protein (p-CREB) and glial fibrillary acidic protein (GFAP) of the spinal dorsal horn was evaluated by western blotting and an immunofluorescence histochemical method, respectively. RESULTS: Intragastric administration of SDF (100, 200, 400 mg/kg) alleviated significantly SNI-induced mechanical hypersensitivity, as PMWT increased in a dose-dependent manner. Moreover, SDF not only reduced the level of NO, NOS, TNF alpha and IL-1beta, but also upregulated the level of IL-10 in the spinal dorsal horn of SNI rats. At the same time, SDF (100, 200, 400 mg/kg) could inhibit the expression of FGFR3, GFAP and p-CREB in the spinal dorsal horn. CONCLUSION: SDF has potentially reduced mechanical hypersensitivity induced by SNI model of neuropathic pain which may be attributed to inhibition of astrocytic function (like release pro-inflammatory cytokines) and NO release as well as p-CREB activation in the spinal dorsal horn. PMID- 26547537 TI - Antileishmanial activity and trypanothione reductase effects of terpenes from the Amazonian species Croton cajucara Benth (Euphorbiaceae). AB - BACKGROUND: Leishmaniasis comprises several infectious diseases caused by protozoa parasites of Leishmania genus. In recent years, there has been a growing interest in the therapeutic use of natural products to treat parasitic diseases. Among them Croton cajucara Benth. (Euphorbiaceae) is a plant found in the Amazonian region with a history of safe use in folk medicine. PURPOSE: The purpose of this study was to investigate the effects of clerodane diterpenes, trans-dehydrocrotonin (DCTN), trans-crotonin (CTN) and acetylaleuritolic acid (AAA) obtained from powdered bark of C. cajucara against promastigotes, axenic and intracellular amastigotes of Leishmania amazonensis. Furthermore, the effects of DCTN and CTN on the trypanotiona reductase enzyme were also investigated. The extraction of the terpenes was carried out as previously reported (Maciel et al., 1998; 2003). METHODS: The effect of the isolated compounds (DCTN, CTN and AAA) from the bark of C. cajucara was assessed in vitro against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis by counting of remaining parasites in a Neubauer chamber in comparison to pentamidine used as standard drug. The action of natural products on trypanothione reductase was assessed using soluble protein fraction of promastigotes. The assays were performed by incubation with HEPES, EDTA, NADPH and trypanothione disulfide to quantify the NAPH consumption by TryR. RESULTS: The results showed very high efficacy, especially of the diterpene DCTN, against promastigotes (IC50 = 6.30 +/ 0.06 ug/ml) and axenic amastigotes (IC50 = 19.98 +/- 0.05 ug/ml) of L. amazonenesis. The cytotoxic effect of the best active natural product was evaluated on mouse peritoneal infected macrophages (IC50 = 0.47 +/- 0.03 ug/ml in 24 h of culture), and the treatment revealed that DCTN never reaches toxic concentrations while reducing the infection and, most importantly, with no toxicity (>100 ug/ml with 0% of macrophage kill) when compared to pentamidine (37.5 ug/ml with 100% of macrophage kill). Furthermore, all of the natural products assayed on the trypanothione reductase enzyme inhibited the enzyme activity compared to the control. CONCLUSION: Clerodane diterpenes from C. cajucara showed promising in vitro antileishmanial effects against L. amazonensis, specially the DCTN with no macrophage toxicity up to the assayed concentration. In addition, the action on trypanothione reductase enzyme revealed a possible mechanism of action. PMID- 26547538 TI - Precision Public Health for the Era of Precision Medicine. PMID- 26547539 TI - Abuse in Childhood or Adolescence and Gestational Diabetes: A Retrospective Cohort Study. AB - INTRODUCTION: Early life abuse has been linked to later Type 2 diabetes, but its association with gestational diabetes has not been examined. The aim of this study was to examine the association between childhood and adolescent abuse victimization and risk of gestational diabetes in the Nurses' Health Study II. METHODS: Participants were asked about experiences of physical and sexual abuse in childhood or adolescence in 2001 and about history of pregnancy complications in 2009. Mothers of singleton live births who provided information on their abuse history comprised the study sample. Modified Poisson regression was used to estimate risk ratios and 95% CIs for gestational diabetes as a function of physical and sexual abuse victimization. Analyses were conducted in 2014-2015. RESULTS: Of 45,550 women in the analysis, 8% reported severe physical abuse and 11% reported forced sexual activity in childhood or adolescence. Approximately 3% (n=3,181) of pregnancies were complicated by gestational diabetes. In adjusted models, severe physical abuse was associated with a 42% greater gestational diabetes risk (risk ratio=1.42, 95% CI=1.21, 1.66) relative to no physical abuse. Forced sexual activity was associated with a 30% greater risk (95% CI=1.14, 1.49). Women with histories of both physical and sexual abuse were at higher risk than women exposed to a single type of abuse. These associations were not explained by overweight status in early adulthood or prior to pregnancy. CONCLUSIONS: Childhood and adolescent victimization is associated with increased risk of gestational diabetes in adult women. PMID- 26547541 TI - Confessions of a Square Peg. PMID- 26547540 TI - Utilization of Preventive Health Care in Adults and Children With Eczema. AB - INTRODUCTION: Chronic disease is a barrier to delivery of preventive health care and health maintenance. However, health behaviors of adults and children with eczema, a chronic skin disorder, have not been examined. This study examined associations of eczema with vaccination, disease screening, health maintenance, and healthcare utilization. METHODS: This study investigated 34,613 adults and 13,298 children from the 2012 National Health Interview Survey, a prospective questionnaire-based study. Data were analyzed between August 2014 and January 2015. RESULTS: Adult eczema was associated with higher odds of vaccination for tetanus (OR [95% CI]=1.37 [1.22, 1.54]); influenza (1.23 [1.10, 1.37]); hepatitis A (1.21 [1.04, 1.41]) and B (1.21 [1.07, 1.35]); human papilloma virus (1.66 [1.32, 2.08]); and pneumonia (1.35 [1.19, 1.54]), but not herpes zoster virus (1.07 [0.87, 1.31]). Adult eczema was associated with increased measurement of blood glucose (1.29 [1.16, 1.44]); cholesterol (1.19 [1.06, 1.34]); blood pressure (1.84 [1.56, 2.08]); and HIV infection (1.50 [1.34, 1.70]), but not Pap smears (1.11 [0.95, 1.30]); colon cancer screening (p=0.17); or mammograms (p=0.63). Adults with eczema were more likely to interact with general doctors, mid-level providers, mental health professionals, eye doctors, podiatrists, chiropractors, therapists, obstetrician/gynecologists, and other specialists (p<=0.01). Childhood eczema was associated with higher rates of vaccination for influenza (p<0.0002); well child checkups (p=0.002); and interaction with most types of healthcare providers (p<=0.01). Many associations remained significant in multivariate models controlling for sociodemographics and healthcare interaction frequency. CONCLUSIONS: Eczema in adults and children is associated with greater utilization of preventive health care and health maintenance, but not cancer screening. PMID- 26547542 TI - Tobacco Exposure and Children: A Changing Landscape. PMID- 26547544 TI - Latino Parents' Insight on Optimal Sleep for Their Preschool-Age Child: Does Context Matter? AB - OBJECTIVE: Insufficient sleep is a risk factor for pediatric obesity. Latino children are among those groups in which both short sleep duration and obesity are prevalent. Therefore, this study sought to explore Latino parents' views about ideal sleep duration and sleep-related practices for their preschool-age children in an urban setting. METHODS: Between October 2013 and January 2014, Latino parents of 2- to 5-year-old children were interviewed at 3 pediatric clinics (San Francisco, Calif). Using a semistructured interview guide, parents were asked to describe bedtime routines and sleep practices of their preschool age children, including behavioral, parental, social, and contextual factors that may affect children's sleep. Interviews were conducted in Spanish and English. Parents also completed a brief survey on demographic information. Interviews were analyzed on the basis of a priori and emergent themes. RESULTS: Latino parents (n = 18) were mostly female, with a mean age of 31 years; most were foreign born; and more than half had a monthly household income of $2000 or less. The following themes emerged: parents' ideas about optimal sleep duration for their preschool age child, consistent bedtime routines, room sharing and bed sharing, parent work and child school schedules that affect children's sleep, and crowded housing and neighborhood noise that disrupt children's sleep. CONCLUSIONS: These findings increase our understanding of the factors related to achieving optimal sleep duration among Latino children living in urban and often crowded housing. Findings could be used to inform future research on how to increase parental knowledge of healthy sleep practices and adequate sleep among Latino parents of young children. PMID- 26547543 TI - A Comparison of Ambulatory Care Sensitive Hospitalizations Among Children With and Without Autism Spectrum Disorder. AB - OBJECTIVE: To compare the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD) and to compare inpatient health care utilization (total charges and length of stay) for the same conditions in children with and without ASD. METHODS: The 2009 Kids' Inpatient Database was used to examine hospitalizations for ACSC in children within 3 cohorts: those with ASD, those with chronic conditions (CC) without ASD, and those with no CC. RESULTS: The proportion of hospitalizations for ACSC in the ASD cohort was 55.9%, compared with 28.2% in the CC cohort and 22.9% in the no-CC cohort (P < .001). Hospitalized children with ASD were more likely to be admitted for a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies compared with the no-CC cohort. Compared with the CC cohort, the ASD cohort was more likely to be admitted for mental health conditions, epilepsy, constipation, dehydration, and underweight. Hospitalized children with ASD admitted for mental health conditions had significantly higher total charges and longer LOS compared with the other 2 cohorts. CONCLUSIONS: The proportion of potentially preventable hospitalizations is higher in hospitalized children with ASD compared with children without ASD. These data underscore the need to improve outpatient care of children with ASD, especially in the areas of mental health care and seizure management. Future research should focus on understanding the reasons for increased inpatient health care utilization in children with ASD admitted for mental health conditions. PMID- 26547546 TI - Characterization and quantification of freezing of gait in Parkinson's disease: Can detection algorithms replace clinical expert opinion? AB - Freezing of gait is a paroxysmal phenomenon that is frequently reported by the parkinsonian patients or their entourage. The phenomenon significantly alters quality of life but is often difficult to characterize in the physician's office. In the present review, we focus on the clinical characterization and quantification of freezing of gait. Various biomechanical methods (based mainly on time-frequency analysis) can be used to determine time-domain characteristics of freezing of gait. Methods already used to study non-gait freezing of other effectors (the lower limbs, upper limbs and orofacial area) are also being developed for the analysis of freezing in functional magnetic resonance imaging protocols. Here, we review the reliability of these methods and compare them with reliability of information obtained from physical examination and detailed analysis of the patient's medical history. PMID- 26547545 TI - Screening for Adolescent Problematic Internet Use: Validation of the Problematic and Risky Internet Use Screening Scale (PRIUSS). AB - OBJECTIVE: Problematic Internet use (PIU) is an emerging health concern that lacks screening measures validated for use with adolescents and young adults. This study aimed to validate the Problematic and Risky Internet Use Screening Scale (PRIUSS) for use with older adolescents and to increase its clinical utility by determining scoring guidelines and assessing the relationship between PIU and other mental health conditions. METHODS: This cross-sectional survey study took place at a large, public Midwestern university among 330 older adolescents aged 18 to 25 years. Confirmatory factor analysis and Spearman's correlations were used to assess the PRIUSS' structural and construct validity, respectively. A risk-based scoring cutoff was estimated using a Bayesian latent class modeling approach to computing a receiver operating characteristic curve. RESULTS: The confirmatory factor analysis indices for the 3-factor model indicated an acceptable fit (goodness-of-fit index 0.89, root mean square error of approximation 0.07). A cutoff of 25 (sensitivity 0.80, 95% confidence interval [CI] 0.47-0.99; specificity 0.79, 95% CI 0.73-0.84) is proposed for identifying those at risk for PIU. Participants at risk for PIU were at significantly greater odds of also reporting symptoms of attention-deficit/hyperactivity disorder (odds ratio [OR] 2.36 95% CI 1.21-4.62, P = .009), depression (OR 3.25, 95% CI 1.65 6.42, P = .008), and social anxiety (OR 3.77, 95% CI 2.06-6.89, P < .000). CONCLUSIONS: The PRIUSS demonstrated validity as a PIU screening instrument for adolescents and young adults. Screening for PIU may also help to identify those at high reciprocal risk for other mental health conditions. PMID- 26547547 TI - Gait post-stroke: Pathophysiology and rehabilitation strategies. AB - We reviewed neural control and biomechanical description of gait in both non disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait. PMID- 26547548 TI - Assessment of knowledge, accessibility and utilization of palliative care services among adult cancer patients at Tikur Anbesa Specialized Hospital, Addis Ababa, Ethiopia, 2014: a cross-sectional institution based study. AB - BACKGROUND: Cancer has been the leading cause of death worldwide for more than two decades. More than 150,000 cancer cases were estimated to exist in Ethiopia each year. The goal of cancer palliative care (PC) services are to prevent and relieve suffering and to support the best possible quality of life (QOL) for patients and their families, regardless of the stage of disease or the need for other therapies. This study attempted to assess the knowledge, accessibility and Utilization of PC Services for adult cancer patients by their perspective at Tikur Anbesa Specialized Hospital (TASH), Addis Ababa, Ethiopia. METHOD: A cross sectional Institution based study was conducted among respondents who had Cancer at TASH. TASH was the only referral center of PC and cancer treatment in Ethiopia. The Hospital was selected for this study purposively. Data was collected by interviewing the client's using a pretested Amharic version questionnaire. During the survey, 384 respondents with cancer were interviewed. Data entry was done using Epi Info version 3.5.2 and exported to SPSS version 20 for analysis. Logistic regression model was applied to control confounders. RESULT: Of the total clients interviewed, more than 62.2 % respondents had previous knowledge for cancer PC services. About 86 % of client's were in the age 35 years and older. About 9 out of 10 (89.8 %) respondents reported problems on accessibility of PC services. Respondents previous knowledge of PC services (AOR = 26.9, 95 % CI 12.3, 59), presence of little (more than 75 % of physical problems/symptoms responded) physical well being of the respondents (AOR = 3.1, 95 % CI 1.96, 4.9), full (all social relationship problems responded as good/positive by respondents) social well being of the respondents (AOR = 1.7, 95 % CI 1.01, 2.8); monthly income $US 25-50 of the respondents (AOR = 0.25, 95 % CI 0.09, 0.7) and marital status single (never married) (AOR = 55.4, 95 % CI 1.2, 2660.4) were significantly associated with respondents utilization of PC services. CONCLUSION: High number of respondents reported problems on accessibility of PC services for cancer in TASH and more than just an average of respondents REPORTED presence of previous knowledge. Respondent's previous knowledge about services, physical well being, social well being, income and marital status were a concern for utilization of cancer PC services at TASH. Health care providers at TASH will be recommended to have a sustainable health education session program on cancer PC services to adult clients after diagnosis of cancer. PMID- 26547549 TI - The importance of the belief that "light" cigarettes are smoother in misperceptions of the harmfulness of "light" cigarettes in the Republic of Korea: a nationally representative cohort study. AB - BACKGROUND: A number of countries have banned misleading cigarette descriptors such as "light" and "low-tar" as called for by the WHO Framework Convention on Tobacco Control. These laws, however, do not address the underlying cigarette design elements that contribute to misperceptions about harm. This is the first study to examine beliefs about "light" cigarettes among Korean smokers, and the first to identify factors related to cigarette design that are associated with the belief that "light" cigarettes are less harmful. METHODS: We analysed data from Wave 3 of the ITC Korea Survey, a telephone survey of a nationally representative sample of 1,753 adult smokers, conducted October - December 2010. A multinomial logistic regression was used to examine which factors were associated with the belief that "light" cigarettes are less harmful than regular cigarettes. RESULTS: One quarter (25.0 %) of smokers believed that "light" cigarettes are less harmful than regular cigarettes, 25.8 % believed that smokers of "light" brands take in less tar, and 15.5 % held both of these beliefs. By far the strongest predictor of the erroneous belief that "light" cigarettes are less harmful was the belief that "light" cigarettes are smoother on the throat and chest (p < 0.001, OR = 44.8, 95 % CI 23.6-84.9). CONCLUSIONS: The strong association between the belief that "light" cigarettes are smoother on the throat and chest and the belief that "light" cigarettes are less harmful, which is consistent with previous research, provides further evidence of the need to not only ban "light" descriptors, but also prohibit cigarette design and packaging features that contribute to the perception of smoothness. PMID- 26547550 TI - Implementation of the Community Health Assistant (CHA) Cadre in Zambia: A Process Evaluation to Guide Future Scale-Up Decisions. AB - Universal health coverage requires an adequate health workforce, including community health workers (CHWs) to reach rural communities. To improve healthcare access in rural areas, in 2010 the Government of Zambia implemented a national CHW strategy that introduced a new cadre of healthcare workers called community health assistants (CHAs). After 1 year of training the pilot class of 307 CHAs deployed in September 2012. This paper presents findings from a process evaluation of the barriers and facilitators of implementation of the CHA pilot, along with how evidence was used to guide ongoing implementation and scale-up decisions. Qualitative inquiry was used to assess implementation during the first 6 months of the program rollout, with 43 in-depth individual and 32 small group interviews across five respondent types: CHAs, supervisors, volunteer CHWs, community members, and district leadership. Potential 'implementation moderators' were explored using deductive coding and thematic analysis of participant perspectives on community acceptance of CHAs, supervision support mechanisms, and coordination with volunteer CHWs, and health system integration of a new cadre. Community acceptance of CHAs was generally high, but coordination between CHAs and existing volunteer CHWs presented some challenges. The supervision support system was found to be inconsistent, limiting assurance of consistent quality care delivered by CHAs. Underlying health system weaknesses regarding drug supply and salary payments furthermore hindered incorporation of a new cadre within the national health system. Recommendations for implementation and future scale based on the process evaluation findings are discussed. PMID- 26547551 TI - Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats. AB - Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic alpha-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 +/- 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 +/- 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes. PMID- 26547552 TI - The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis. AB - Congenital scoliosis is a condition characterized by spinal curvature beyond the physiological norm. The molecular mechanisms underlying the pathogenesis of congenital scoliosis are beginning to be clarified; however, the genes related to congenital scoliosis are still unknown. We herein report the results of a comprehensive analysis of gene expression in the spines from a rat model of congenital kyphoscoliosis obtained using DNA microarrays. The rats (Ishibashi rats, IS) showed decreased expression levels of genes associated with bone formation, such as those associated with retinol metabolism and type I collagen. Interestingly, the flexion sites of the IS rats showed low expression levels of tropomyosin receptor kinases (Trks: TrkA, TrkB, and TrkC), which belong to the neurotrophic receptor tyrosine kinase family. Moreover, this phenomenon was observed only in the flexion sites of the spine, and the expression levels of Trks in other parts of the spine in these rats were normal. The decreased expression levels of Trks were observed at both the mRNA and protein levels. We also observed that the number of Trk-immunopositive cells in the lumbar spine in the IS rats was lower than that in wild-type rats. These findings indicate that the Trks have an important function in regulating normal bone formation, and provide a molecular explanation for the pathogenesis of congenital kyphoscoliosis. PMID- 26547553 TI - When Should We Use Care Robots? The Nature-of-Activities Approach. AB - When should we use care robots? In this paper we endorse the shift from a simple normative approach to care robots ethics to a complex one: we think that one main task of a care robot ethics is that of analysing the different ways in which different care robots may affect the different values at stake in different care practices. We start filling a gap in the literature by showing how the philosophical analysis of the nature of healthcare activities can contribute to (care) robot ethics. We rely on the nature-of-activities approach recently proposed in the debate on human enhancement, and we apply it to the ethics of care robots. The nature-of-activities approach will help us to understand why certain practice-oriented activities in healthcare should arguably be left to humans, but certain (predominantly) goal-directed activities in healthcare can be fulfilled (sometimes even more ethically) with the assistance of a robot. In relation to the latter, we aim to show that even though all healthcare activities can be considered as practice-oriented, when we understand the activity in terms of different legitimate 'fine-grained' descriptions, the same activities or at least certain components of them can be seen as clearly goal-directed. Insofar as it allows us to ethically assess specific functionalities of specific robots to be deployed in well-defined circumstances, we hold the nature-of-activities approach to be particularly helpful also from a design perspective, i.e. to realize the Value Sensitive Design approach. PMID- 26547555 TI - Information and Communication Technologies, Genes, and Peer-Production of Knowledge to Empower Citizens' Health. AB - The different and seemingly unrelated practices of Information and Communication Technologies (ICT) used to collect and share personal and scientific data within networked communities, and the organized storage of human genetic samples and information-namely biobanking-have merged with another recent epistemic and social phenomenon, namely scientists and citizens collaborating as "peers" in creating knowledge (or peer-production of knowledge). These different dimensions can be found in joint initiatives where scientists-and-citizens use genetic information and ICT as powerful ways to gain more control over their health and the environment. While this kind of initiative usually takes place only after rights have been infringed (or are put at risk)-as the two cases presented in the paper show-collaborative scientists-and-citizens' knowledge should be institutionally allowed to complement and corroborate official knowledge supporting policies. PMID- 26547556 TI - A Simple Framework for Evaluating Authorial Contributions for Scientific Publications. AB - A simple tool is provided to assist researchers in assessing contributions to a scientific publication, for ease in evaluating which contributors qualify for authorship, and in what order the authors should be listed. The tool identifies four phases of activity leading to a publication-Conception and Design, Data Acquisition, Analysis and Interpretation, and Manuscript Preparation. By comparing a project participant's contribution in a given phase to several specified thresholds, a score of up to five points can be assigned; the contributor's scores in all four phases are summed to yield a total "contribution score", which is compared to a threshold to determine which contributors merit authorship. This tool may be useful in a variety of contexts in which a systematic approach to authorial credit is desired. PMID- 26547557 TI - Exploring multiple quantitative trait loci models of hepatic fibrosis in a mouse intercross. AB - Most common diseases are attributed to multiple genetic variants, and the feasibility of identifying inherited risk factors is often restricted to the identification of alleles with high or intermediate effect sizes. In our previous studies, we identified single loci associated with hepatic fibrosis (Hfib1 Hfib4). Recent advances in analysis tools allowed us to model loci interactions for liver fibrosis. We analysed 322 F2 progeny from an intercross of the fibrosis susceptible strain BALB/cJ and the resistant strain FVB/NJ. The mice were challenged with carbon tetrachloride (CCl4) for 6 weeks to induce chronic hepatic injury and fibrosis. Fibrosis progression was quantified by determining histological fibrosis stages and hepatic collagen contents. Phenotypic data were correlated to genome-wide markers to identify quantitative trait loci (QTL). Thirteen susceptibility loci were identified by single and composite interval mapping, and were included in the subsequent multiple QTL model (MQM) testing. Models provided evidence for susceptibility loci with strongest association to collagen contents (chromosomes 1, 2, 8 and 13) or fibrosis stages (chromosomes 1, 2, 12 and 14). These loci contained the known fibrosis risk genes Hc, Fasl and Foxa2 and were incorporated in a fibrosis network. Interestingly the hepatic fibrosis locus on chromosome 1 (Hfib5) connects both phenotype networks, strengthening its role as a potential modifier locus. Including multiple QTL mapping to association studies adds valuable information on gene-gene interactions in experimental crosses and human cohorts. This study presents an initial step towards a refined understanding of profibrogenic gene networks. PMID- 26547560 TI - Optimization of the Timepix chip to measurement of radon, thoron and their progenies. AB - Radon and thoron as well as their short-lived progenies are decay products of the radium and thorium series decays. They are the most important radionuclide elements with respect to public exposure. To utilize the semiconductor pixel radiation Timepix chip for the measurement of active and real-time alpha particles from radon, thoron and their progenies, it is necessary to check the registration and visualization of the chip. An energy check for radon, thoron and their progenies, as well as for (241)Am and(210)Po sources, was performed using the radon and thoron chambers at NIRS (National Institute of Radiological Sciences). The check found an energy resolution of 200 keV with a 14% efficiency as well as a linear dependency between the channel number (cluster volume) and the energy. The coefficient of determination r(2) of 0.99 for the range of 5 to 9 MeV was calculated. In addition, an offset for specific Timepix configurations between pre-calibration for low energy from 6 to 60 keV, and the actual calibration for alpha particles with energies from 4000 to 9000 keV, was detected. PMID- 26547558 TI - Cassava root membrane proteome reveals activities during storage root maturation. AB - Cassava (Manihot esculenta Crantz) is one of the most important crops of Thailand. Its storage roots are used as food, feed, starch production, and be the important source for biofuel and biodegradable plastic production. Despite the importance of cassava storage roots, little is known about the mechanisms involved in their formation. This present study has focused on comparison of the expression profiles of cassava root proteome at various developmental stages using two-dimensional gel electrophoresis and LC-MS/MS. Based on an anatomical study using Toluidine Blue, the secondary growth was confirmed to be essential during the development of cassava storage root. To investigate biochemical processes occurring during storage root maturation, soluble and membrane proteins were isolated from storage roots harvested from 3-, 6-, 9-, and 12-month-old cassava plants. The proteins with differential expression pattern were analysed and identified to be associated with 8 functional groups: protein folding and degradation, energy, metabolism, secondary metabolism, stress response, transport facilitation, cytoskeleton, and unclassified function. The expression profiling of membrane proteins revealed the proteins involved in protein folding and degradation, energy, and cell structure were highly expressed during early stages of development. Integration of these data along with the information available in genome and transcriptome databases is critical to expand knowledge obtained solely from the field of proteomics. Possible role of identified proteins were discussed in relation with the activities during storage root maturation in cassava. PMID- 26547559 TI - Interaction of Mg with heavy metals (Cu, Cd) in T. aestivum with special reference to oxidative and proline metabolism. AB - Little effort has been made to understand the influence of Mg on cellular processes of plant cell during Cu and Cd toxicities. The present work demonstrates the influence of magnesium (Mg) on copper (Cu) and cadmium (Cd) toxicity on Triticum aestivum (Wheat). We measured a range of parameters related to oxidative stress in wheat exposed to Cu or Cd toxicity in media with different concentrations of Mg. Decreasing Mg concentration significantly exacerbated Cu and Cd toxicity and optimum supply of Mg improved the growth and decreased the toxicity-induced oxidative stress (a substantial decline in the amount of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in root and shoot tissues). Activity of antioxidant enzymes-superoxide dismutase (SOD), ascorbae peroxidase (APX), catalase (CAT) was restored upon optimum Mg concentration in the presence of Cu and Cd toxicity. An increase in proline concentration in roots and shoots that was triggered by Cu and Cd exposure was partly reversed. This was due to decline in pyrroline-5-carboxylate synthetase (P5CS) and pyrroline-5-carboxylate reductase (P5CR) activity and enhanced proline dehydrogenase (PDH) activity. In conclusion, decreasing supply of Mg effectively exacerbated the toxicities of Cu and Cd in wheat. PMID- 26547561 TI - Pallidal neuronal apolipoprotein E in pantothenate kinase-associated neurodegeneration recapitulates ischemic injury to the globus pallidus. AB - Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive movement disorder that is due to mutations in PANK2. Pathologically, it is a member of a class of diseases known as neurodegeneration with brain iron accumulation (NBIA) and features increased tissue iron and ubiquitinated proteinaceous aggregates in the globus pallidus. We have previously determined that these aggregates represent condensed residue derived from degenerated pallidal neurons. However, the protein content, other than ubiquitin, of these aggregates remains unknown. In the present study, we performed biochemical and immunohistochemical studies to characterize these aggregates and found them to be enriched in apolipoprotein E that is poorly soluble in detergent solutions. However, we did not determine a significant association between APOE genotype and the clinical phenotype of disease in our database of 81 cases. Rather, we frequently identified similar ubiquitin- and apolipoprotein E-enriched lesions in these neurons in non-PKAN patients in the penumbrae of remote infarcts that involve the globus pallidus, and occasionally in other brain sites that contain large gamma-aminobutyric acid (GABA)ergic neurons. Our findings, taken together, suggest that tissue or cellular hypoxic/ischemic injury within the globus pallidus may underlie the pathogenesis of PKAN. PMID- 26547562 TI - Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15 years Experience. AB - BACKGROUND: The treatment of long-chain mitochondrial beta-oxidation disorders (LC-FOD) with a low fat-high carbohydrate diet, a diet rich in medium-even-chain triglycerides (MCT), or a combination of both has been associated with high morbidity and mortality for decades. The pathological tableau appears to be caused by energy deficiency resulting from reduced availability of citric acid cycle (CAC) intermediates required for optimal oxidation of acetyl-CoA. This hypothesis was investigated by diet therapy with carnitine and anaplerotic triheptanoin (TH). METHODS: Fifty-two documented LC-FOD patients were studied in this investigation (age range: birth to 51 years). Safety monitoring included serial quantitative measurements of routine blood chemistries, blood levels of carnitine and acylcarnitines, and urinary organic acids. RESULTS: The average frequency of serious clinical complications were reduced from ~60% with conventional diet therapy to 10% with TH and carnitine treatment and mortality decreased from ~65% with conventional diet therapy to 3.8%. Carnitine supplementation was uncomplicated. CONCLUSION: The energy deficiency in LC-FOD patients was corrected safely and more effectively with the triheptanoin diet and carnitine supplement than with conventional diet therapy. Safe intervention in neonates and infants will permit earlier intervention following pre-natal diagnosis or diagnosis by expanded newborn screening. PMID- 26547563 TI - [Cardiac arrest in dialysis patients: Risk factors, preventive measures and management in 2015]. AB - Patients undergoing hemodialysis have a 10 to 20 times higher risk of sudden cardiac arrest (SCA) than the general population. Sudden cardiac death is a rare event (approximately 1 event per 10,000 sessions) but has a very high mortality rate. Epidemiological data comes almost exclusively from North American studies; there is a great lack of European data on the subject. Ventricular arrhythmia is the main mechanism of sudden cardiac deaths in dialysis patients. These patients develop increased sensitivity mainly due to a high prevalence of severe ischemic heart disease and left ventricular hypertrophy and to a frequent trigger event: electrolytic and plasma volume shifts during dialysis sessions. Unfortunately, accurate predictive markers of SCA do not exist, however some primary prevention trials using beta-blockers or angiotensin II receptor blockers are encouraging, while the use of implantable cardioverter defibrillators in the population of chronic dialysis patients remains controversial. Identification of patients at risk, minimizing trigger events such as electrolytic shifts and improving team skills in the diagnosis and initial resuscitation with the latest recommendations from 2010 seem necessary to reduce incidence and improve survival in this high risk population. Organization of European studies would also allow a more accurate view of this reality in our dialysis units. PMID- 26547564 TI - Effect of bait decomposition on the attractiveness to species of Diptera of veterinary and forensic importance in a rainforest fragment in Brazil. AB - Insects associated with carrion can have parasitological importance as vectors of several pathogens and causal agents of myiasis to men and to domestic and wild animals. We tested the attractiveness of animal baits (chicken liver) at different stages of decomposition to necrophagous species of Diptera (Calliphoridae, Fanniidae, Muscidae, Phoridae and Sarcophagidae) in a rainforest fragment in Brazil. Five types of bait were used: fresh and decomposed at room temperature (26 degrees C) for 24, 48, 72 and 96 h. A positive correlation was detected between the time of decomposition and the abundance of Calliphoridae and Muscidae, whilst the abundance of adults of Phoridae decreased with the time of decomposition. Ten species of calliphorids were registered, of which Chrysomya albiceps, Chrysomya megacephala and Chloroprocta idioidea showed a positive significant correlation between abundance and decomposition. Specimens of Sarcophagidae and Fanniidae did not discriminate between fresh and highly decomposed baits. A strong female bias was registered for all species of Calliphoridae irrespective of the type of bait. The results reinforce the feasibility of using animal tissues as attractants to a wide diversity of dipterans of medical, parasitological and forensic importance in short-term surveys, especially using baits at intermediate stages of decomposition. PMID- 26547566 TI - Genome Characteristics of a Novel Type I Methanotroph (Sn10-6) Isolated from a Flooded Indian Rice Field. AB - Flooded rice fields are important sources of atmospheric methane. Aerobic methanotrophs living in the vicinity of rice roots oxidize methane and act as environmental filters. Here, we present genome characteristics of a gammaproteobacterial methanotroph, isolate Sn10-6, which was isolated from a rice rhizosphere of a flooded field in India. Sn10-6 has been identified as a member of a putative novel genus and species within the family Methylococcaceae (Type I methanotrophs). The draft genome of Sn10-6 showed pathways for the following: methane oxidation, formaldehyde assimilation (RuMP), nitrogen fixation, conversion of nitrite to nitrous oxide, and other interesting genes including the ones responsible for survival in the rhizosphere environment. The majority of genes found in this genome were most similar to Methylovulum miyakonese which is a forest isolate. This draft genome provided insight into the physiology, ecology, and phylogeny of this gammaproteobacterial methanotroph. PMID- 26547565 TI - Human TNF-alpha induces differential protein phosphorylation in Schistosoma mansoni adult male worms. AB - Schistosoma mansoni and its vertebrate host have a complex and intimate connection in which several molecular stimuli are exchanged and affect both organisms. Human tumor necrosis factor alpha (hTNF-alpha), a pro-inflammatory cytokine, is known to induce large-scale gene expression changes in the parasite and to affect several parasite biological processes such as metabolism, egg laying, and worm development. Until now, the molecular mechanisms for TNF-alpha activity in worms are not completely understood. Here, we aimed at exploring the effect of hTNF-alpha on S. mansoni protein phosphorylation by 2D gel electrophoresis followed by a quantitative analysis of phosphoprotein staining and protein identification by mass spectrometry. We analyzed three biological replicates of adult male worms exposed to hTNF-alpha and successfully identified 32 protein spots with a statistically significant increase in phosphorylation upon in vitro exposure to hTNF-alpha. Among the differentially phosphorylated proteins, we found proteins involved in metabolism, such as glycolysis, galactose metabolism, urea cycle, and aldehyde metabolism, as well as proteins related to muscle contraction and to cytoskeleton remodeling. The most differentially phosphorylated protein (30-fold increase in phosphorylation) was 14-3-3, whose function is known to be modulated by phosphorylation, belonging to a signal transduction protein family that regulates a variety of processes in all eukaryotic cells. Further, 75% of the identified proteins are known in mammals to be related to TNF-alpha signaling, thus suggesting that TNF-alpha response may be conserved in the parasite. We propose that this work opens new perspectives to be explored in the study of the molecular crosstalk between host and pathogen. PMID- 26547567 TI - Deciphering Community Structure of Methanotrophs Dwelling in Rice Rhizospheres of an Indian Rice Field Using Cultivation and Cultivation-Independent Approaches. AB - Methanotrophs play a crucial role in filtering out methane from habitats, such as flooded rice fields. India has the largest area under rice cultivation in the world; however, to the best of our knowledge, methanotrophs have not been isolated and characterized from Indian rice fields. A cultivation strategy composing of a modified medium, longer incubation time, and serial dilutions in microtiter plates was used to cultivate methanotrophs from a rice rhizosphere sample from a flooded rice field in Western India. We compared the cultured members with the uncultured community as revealed by three culture-independent methods. A novel type Ia methanotroph (Sn10-6), at the rank of a genus, and a putative novel species of a type II methanotroph (Sn-Cys) were cultivated from the terminal positive dilution (10(-6)). From lower dilution (10(-4)), a strain of Methylomonas spp. was cultivated. All the three culture-independent analyses, i.e., pmoA clone library, terminal restriction fragment length polymorphism (T RFLP), and metagenomics approach, revealed the dominance of type I methanotrophs. Only metagenomic analysis showed significant presence of type II methanotrophs, albeit in lower proportion (37 %). All the three isolates showed relevance to the methanotrophic community as depicted by uncultured methods; however, the cultivated members might not be the most dominant ones. In conclusion, a combined cultivation and cultivation-independent strategy yielded us a broader picture of the methanotrophic community from rice rhizospheres of a flooded rice field in India. PMID- 26547569 TI - Creatinine Kinase Isoenzyme MB: A Simple Prognostic Marker for Pulmonary Embolism. PMID- 26547568 TI - Diverse Bacterial Groups Contribute to the Alkane Degradation Potential of Chronically Polluted Subantarctic Coastal Sediments. AB - We aimed to gain insight into the alkane degradation potential of microbial communities from chronically polluted sediments of a subantarctic coastal environment using a combination of metagenomic approaches. A total of 6178 sequences annotated as alkane-1-monooxygenases (EC 1.14.15.3) were retrieved from a shotgun metagenomic dataset that included two sites analyzed in triplicate. The majority of the sequences binned with AlkB described in Bacteroidetes (32 +/- 13 %) or Proteobacteria (29 +/- 7 %), although a large proportion remained unclassified at the phylum level. Operational taxonomic unit (OTU)-based analyses showed small differences in AlkB distribution among samples that could be correlated with alkane concentrations, as well as with site-specific variations in pH and salinity. A number of low-abundance OTUs, mostly affiliated with Actinobacterial sequences, were found to be only present in the most contaminated samples. On the other hand, the molecular screening of a large-insert metagenomic library of intertidal sediments from one of the sampling sites identified two genomic fragments containing novel alkB gene sequences, as well as various contiguous genes related to lipid metabolism. Both genomic fragments were affiliated with the phylum Planctomycetes, and one could be further assigned to the genus Rhodopirellula due to the presence of a partial sequence of the 23S ribosomal RNA (rRNA) gene. This work highlights the diversity of bacterial groups contributing to the alkane degradation potential and reveals patterns of functional diversity in relation with environmental stressors in a chronically polluted, high-latitude coastal environment. In addition, alkane biodegradation genes are described for the first time in members of Planctomycetes. PMID- 26547570 TI - Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). AB - Collection and analysis of information on diseases and post-transplant courses of allogeneic hematopoietic stem cell transplant recipients have played important roles in improving therapeutic outcomes in hematopoietic stem cell transplantation. Efficient, high-quality data collection systems are essential. The introduction of the Second-Generation Transplant Registry Unified Management Program (TRUMP2) is intended to improve data quality and more efficient data management. The TRUMP2 system will also expand possible uses of data, as it is capable of building a more complex relational database. The construction of an accessible data utilization system for adequate data utilization by researchers would promote greater research activity. Study approval and management processes and authorship guidelines also need to be organized within this context. Quality control of processes for data manipulation and analysis will also affect study outcomes. Shared scripts have been introduced to define variables according to standard definitions for quality control and improving efficiency of registry studies using TRUMP data. PMID- 26547571 TI - Geographic and income variations in age at diagnosis and incidence of chronic myeloid leukemia. AB - Developing countries have a younger population of CML patients than developed countries. Patterns of age at diagnosis and incidence by geography and gross national income (GNI) are not well understood. A population-based descriptive study was conducted using data from the International Agency for Research on Cancer's population-based registry compilation. Geographical regions were classified according to the United Nations World Macro Regions and Components. Age-Standardized Incidence Rates (ASR) were adjusted to the World Standard Population. Poisson regression was used to assess age-specific interactions. 57.2% were male among 33,690 diagnoses. Median age at diagnosis was lowest in Africa and Asia (47 years) and highest in Oceania (72 years). ASR was lowest in African males (0.61 per 100,000) and Asian females (0.55 per 100,000) and highest in Oceania males and females (1.78 and 0.96 per 100,000, respectively). A significant interaction (p < 0.0001) between age (<50 years and >50 years) and region exists; no significant differences were seen by region in the <50 age group while significant differences by region exist in the >50 age group. Population-based estimates suggest that the median age at diagnosis and incidence varies by region. Geographic and income heterogeneity suggest an important effect of environment that warrants further studies. PMID- 26547572 TI - Parents' Opinion About a Routine Head-to-Toe Examination of Children as a Screening Instrument for Child Abuse and Neglect in Children Visiting the Emergency Department. AB - INTRODUCTION: To improve detection of child abuse and neglect (CAN), many emergency departments use screening methods. Apart from diagnostic accuracy, possible harms of screening methods are important to consider, especially because most children are not abused and do not benefit from screening. We performed a systematic literature review to assess parents' opinions about CAN screening, in which we could only include 7 studies, all reporting that the large majority of participating parents favor screening. Recently, a complete physical examination (called "top-toe" inspection [TTI], a fully undressed inspection of the child) was implemented as a CAN screening method at the emergency department of a teaching hospital in The Netherlands. This study describes parents' opinions about the TTI. METHODS: We used a questionnaire to assess parents' opinions about the TTI of their children when visiting the emergency department. During the study period, 1000 questionnaires were distributed by mail. RESULTS: In total, 372 questionnaires were returned (37%). A TTI was performed for 194 children (52%). The overall attitude of parents whose children underwent a TTI was positive; 77.3% of the respondents found the TTI acceptable, and 1.5% (N = 3) found it unacceptable. Seventy percent of the respondents agreed with the theorem that all children who visit the emergency department should have a TTI performed, and 7.3% (N = 14) disagreed. DISCUSSION: Contrary to what is commonly believed, both in our systematic literature review and in our questionnaire study, the majority of participating parents agree with screening for CAN in general and with the TTI specifically. Sharing the results of this study with ED personnel and policy makers could take away prejudices about perceived disagreement of parents, thereby improving implementation of and adherence to CAN screening. PMID- 26547573 TI - Differences Between Emergency Nurse Perception and Patient Reported Experience With an ED HIV and Hepatitis C Virus Screening Program. AB - INTRODUCTION: Nontargeted human immunodeficiency virus (HIV) screening and targeted hepatitis C virus (HCV) screening for selected high-risk patients (those born between 1945 and 1965 and those who report injection drug use) was integrated into our ED triage process and carried out by nurses. Determining whether emergency nurses accurately perceive what patients experience is important to know because staff misperceptions may pose a barrier to program adherence and sustainability. METHODS: We performed a cross-sectional survey study of emergency nurses and patients to assess the accuracy of emergency nurses' perception of patient experience with the HIV/HCV screening program. Respondents evaluated their level of agreement using a 5-item Likert scale for 9 statements across 4 domains related to the patient experience with the screening process (satisfaction, sense of autonomy, sense of privacy, and comfort level). RESULTS: Surveys were completed by 65 of the 153 eligible emergency nurses (42%). Of the 1040 patients approached, 610 (59%) were eligible, and 491 of the 610 eligible patients (80%) completed surveys. Across all domains, statistically significant differences were found between emergency nurse perception and patient report, P < .001. Emergency nurses perceived patients to be less satisfied with the screening program, more uncomfortable with being asked screening questions, more concerned about privacy issues, and less likely to feel that the decision to decline screening was autonomous than were patients. DISCUSSION: Emergency nurses not only frequently misperceive how patients experience ED-based HIV/HCV screening, but these misperceptions are skewed toward the negative, representing a type of staff bias. Further research is recommended to determine if such misperceptions adversely affect implementation of screening. PMID- 26547574 TI - Stigma, Anchoring, and Triage Decisions. PMID- 26547575 TI - IV Push Medication Administration: Making Safe Choices; Choosing Best Practice. PMID- 26547576 TI - Use of Intranasal Ketamine for the Severely Agitated or Violent ED Patient. PMID- 26547577 TI - Pterocarpadiols A-D, Rare 6a,11b-Dihydroxypterocarpans from Derris robusta. AB - Four hitherto unknown 6a,11b-dihydroxypterocarpans, namely pterocarpadiols A-D (1 4), were isolated from the ethanol extract of the twigs and leaves of Derris robusta. Their structures were elucidated on the basis of extensive spectroscopic analysis. Pterocarpadiols A-D are a kind of very rare 6a,11b dihydroxypterocarpans, and their presence as markers may be helpful in chemotaxonomical classification. PMID- 26547578 TI - Detection of Magnaporthe oryzae chrysovirus 1 in Japan and establishment of a rapid, sensitive and direct diagnostic method based on reverse transcription loop mediated isothermal amplification. AB - Magnaporthe oryzae chrysovirus 1 (MoCV1) is a mycovirus with a dsRNA genome that infects the rice blast fungus Magnaporthe oryzae and impairs its growth. To date, MoCV1 has only been found in Vietnamese isolates of M. oryzae, and the distribution of this virus in M. oryzae isolates from other parts of the world remains unknown. In this study, using a one-step reverse transcription PCR (RT PCR) assay, we detected a MoCV1-related virus in M. oryzae in Japan (named MoCV1 AK) whose sequence shares considerable similarity with that of the MoCV1 Vietnamese isolate. To establish a system for a comprehensive survey of MoCV1 infection in the field, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for direct detection of the virus. The sensitivity of the RT-LAMP assay was at least as high as that of the one-step RT PCR assay. In addition, we detected MoCV1-AK in M. oryzae-infected oatmeal agar plates and lesions on rice leaves using the RT-LAMP assay without dsRNA extraction, by simple sampling with a toothpick. Preliminary screening of MoCV1 in Japanese M. oryzae isolates indicated that MoCV1 is currently distributed in rice fields in Japan. Our results provide a first example of the application of RT-LAMP for the detection of mycoviruses, which will accelerate surveys for mycovirus infection. PMID- 26547579 TI - Protein kinase R (PKR) plays a pro-viral role in porcine reproductive and respiratory syndrome virus (PRRSV) replication by modulating viral gene transcription. AB - Protein kinase R (PKR) is involved in apoptotic cell death and antiviral activities in response to many virus infections. To reveal the role of PKR in the replication of porcine reproductive and respiratory syndrome virus (PRRSV), we first examined the kinetics of PKR phosphorylation during PRRSV infection. The results showed that PRRSV transiently activates PKR at 12 and 24 h postinfection. Surprisingly, eIF-2alpha, the well-known downstream target of PKR, was significantly phosphorylated compared to mock-infected cells only at 48 and 72 h postinfection. Reduced viral gene transcription, viral protein synthesis, and virus titer were detected in cells transfected with PKR silencing RNA prior to PRRSV infection compared to control silencing RNA transfected cells, indicating a role of PKR in facilitating virus replication. Overall, our data suggest that PKR is not a major contributor to the phosphorylation of eIF-2alpha during PRRSV infection, but it plays a pro-viral role in PRRSV replication by modulating primarily viral gene transcription. PMID- 26547580 TI - The renoprotective effect of shichimotsukokato on hypertension-induced renal dysfunction in spontaneously hypertensive rats. AB - Antihypertensive treatment is highly important to prevent the progression of chronic kidney disease. Shichimotsukokato (SKT), a traditional Japanese medicine (i.e., Kampo formula), lowered systolic blood pressure (SBP) in experimental animal models of hypertension. However, its mechanism of action has not been fully elucidated. We investigated the potential renoprotective mechanism of SKT in spontaneously hypertensive rats (SHRs). Ten-week-old SHRs were randomly divided into four groups (six rats per group). In the SHR control group, the SBP increased remarkably during the 8-week experimental period. In the SHRs, SKT extract administered orally at a daily dose of 0.45 or 0.15 g/kg significantly suppressed the increase in SBP to the same extent as telmisartan administered orally at a daily dose of 0.01 g/kg. At the end of the experiment, blood, urine, and kidney cortex tissue samples were examined. The SKT treatment significantly decreased urinary albumin excretion to nearly the same level as the telmisartan treatment. A notable loss of chloride channel 5 (ClC-5), a chloride channel in the proximal renal tubules, occurred in the SHR control group. Thus, we concluded that SKT administration significantly ameliorated this decrease. The mechanism of SKT in reducing urinary albumin excretion is mediated, at least partly, by prevention of the loss of ClC-5 in the renal cortex of SHRs. PMID- 26547581 TI - Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells. AB - Manool, a diterpene isolated from Salvia officinalis, was evaluated by the XTT colorimetric assay for cytotoxicity and selectivity against different cancer cell lines: B16F10 (murine melanoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), HepG2 (human hepatocellular carcinoma), and MO59J, U343 and U251 (human glioblastoma). A normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare the selectivity of the test substance. Manool exhibited higher cytotoxic activity against HeLa (IC50 = 6.7 +/- 1.1 ug/mL) and U343 (IC50 = 6.7 +/- 1.2 ug/mL) cells. In addition, in the used experimental protocols, the treatment with manool was significantly more cytotoxic for different tumor cell lines than for the normal cell line V79 (IC50 = 49.3 +/- 3.3 ug/mL), and showed high selectivity. These results suggest that manool may be used to treat cancer without affecting normal cells. PMID- 26547582 TI - Integrin beta6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC). AB - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin beta6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of beta6 in PDAC remain largely unknown. In the present study, we investigated the expression of beta6 in PDAC and its potential value as a prognostic factor and therapeutic target. beta6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin beta6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for beta6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin beta6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin beta6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC. PMID- 26547583 TI - The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-kappaB pathway. AB - Oleanolic acid (OA) possesses various pharmacological activities, such as antitumor and anti-inflammation; however, its clinical applications are limited by its relatively weak activities and low bioavailability. In this study, we evaluated the cytotoxic activity of seven novel OA derivatives, one of which, SZC014 [2-(pyrrolidine-1-yl) methyl-3-oxo-olean-12-en-28-oic acid], exhibited the strongest antitumor activity; its anticancer effect on gastric cancer cells and action mechanisms were investigated. The viability of OA and seven synthesized derivatives treating gastric cancer cells was detected using tetrazolium (MTT). Among them, SZC014 exhibited the strongest cytotoxic activity against gastric cancer cells (SGC7901, MGC803, and MKN-45). The effect of SZC014 on cell cycle was identified by propidium iodide (PI) staining assay. The cellular apoptosis induced by SZC014 was tested by annexin V/PI. The cellular morphological changes and ultrastructural structures affected by SZC014 were observed and imaged through inverted phase contrast microscope and transmission electron microscopy. Western blotting was performed to explore the expression of proteins associated with apoptosis (caspase 3, caspase 9, Bax, Bcl-2, and Bcl-xL), autophagy (Beclin 1 and ATG 5), and nuclear factor-kappaB (NF-kappaB) signal pathway, respectively. The cytotoxic activities of all the seven synthesized OA derivatives were stronger than that of OA against gastric cancer cells. SZC014 exhibited stronger cytotoxic activity than other OA derivatives, inhibited the proliferation of gastric cancer cells, besides, induced G2/M phase cell cycle arrest in SGC7901 cells. Both apoptosis and autophagy were found simultaneously in SZC014-treated SGC7901 cells. Caspase-dependent apoptosis induced by SZC014 was confirmed to be associated with upregulation of Bax and downregulation of Bcl-2 and Bcl-xL, while upregulation of Beclin 1 and ATG 5 was inferred to be involved in SZC014-induced autophagy. Moreover, treating cells with SZC014 resulted in a decrease in phosphorylation of IkappaBalpha and NF-kappaB/p65 and NF-kappaB/p65 nuclear translocation. The cytotoxic activities of seven OA derivatives were generally stronger than that of OA, among which, SZC014 possessed the most potent anticancer activity in SGC7901 cells and would be a promising chemotherapic agent for the treatment of gastric cancer. PMID- 26547584 TI - Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma. AB - Succinate dehydrogenase subunit B (SDHB) and pyruvate dehydrogenase kinase 1 (PDK1) play key roles in the regulation of growth and survival of various cancers. This study aimed to investigate expression of SDHB and PDK1 in recurrent nasopharyngeal carcinoma (rNPC) tissues and analyzed the association of SDHB and PDK1 expression with the clinical significance and potential prognostic implication of rNPC. Immunohistochemistry was performed to determine the expression of SDHB and PDK1 in tissues in primary NPC (pNPC) and rNPC patients. Our results revealed that expression of SDHB in rNPC was significantly lower than that in pNPC, while the expression of PDK1 was higher compared to pNPC. The expression levels of SDHB and PDK1 were associated with T stage, N stage, clinical stage, and metastasis of rNPC. Survival analysis showed that patients with low SDHB expression had a significantly shorter overall survival time than those with high SDHB expression. Patients with high PDK1 expression had a shorter survival time than patients with low PDK1 expression. Multivariate analysis showed that the expression of SDHB and PDK1 was an independent predictor for the survival of patients with rNPC. Our results demonstrated that down-regulation of SDHB and up-regulation of PDK1 may be novel biomarkers for predicting advanced tumor progression and unfavorable prognosis in rNPC patients. PMID- 26547585 TI - Quantitative measurement of iNOS expression in melanoma, nasopharyngeal, colorectal, and breast tumors of Tunisian patients: comparative study and clinical significance. AB - Chronic inflammation increases the risk of development of human malignancies. iNOS is an enzyme dominantly expressed during inflammatory reactions and seems to play a critical role in tumorigenesis. Our aim was to assess the iNOS expression in four types of human tumors: breast, colorectal, nasopharyngeal, and melanoma, of Tunisian patients. The level of iNOS was measured by RT-QPCR in tumor specimens. We showed that the expression of iNOS was higher in breast compared to colorectal and nasopharyngeal tumors, whereas in melanoma, the level of iNOS expression was low. Significant associations were found when comparing the iNOS expression in cancers pairs such as melanoma versus colorectal (p < 0.0001), colorectal versus nasopharyngeal (p = 0.0072), and melanoma versus breast (p < 0.0001). Furthermore, iNOS expression correlated with the Breslow thickness, Clark level, and histological subtype in melanoma, while in nasopharyngeal carcinoma, significant association was seen with age at diagnosis, TNM, metastasis, response to treatment, and expression of COX-2. Furthermore, the expression of iNOS correlated with tumor size, TNM, tumor location, and histological type in colorectal cancer, and with tumor size, tumor stage, SBR grade, and triple negative cases in breast cancer. On the other hand, immunohistochemistry analysis shows that the expression of iNOS is observed in the stroma and tumor cells as well. Overall, our results highlight that iNOS is a reliable marker for advanced stage and aggressive behavior for the four types of cancer and might be a potential promising therapeutic target. PMID- 26547586 TI - Increased expression of ESCO1 is correlated with poor patient survival and its role in human bladder cancer. AB - There is increasing evidence suggesting that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) was involved in tumorigenesis. However, its role in bladder cancer remains unclear. In this study, we aimed to study the clinical correlation and biological significance of ESCO1 in bladder cancer. Our results showed that ESCO1 was significantly over-expressed in bladder cancer tissues compared with that in adjacent normal tissues. And, increased ESCO1 expression was significantly associated with higher grade (P < 0.001), higher tumor stage (P = 0.014), and multifocality (P = 0.042). Kaplan-Meier analysis and Cox proportional hazards model were performed to determine the prognostic significance of ESCO1, and the results showed that ESCO1 is a useful prognostic marker for bladder cancer patients. Moreover, we found that ESCO1 knockdown inhibited the growth, migration, and invasion of bladder cancer cells. In conclusion, our findings indicated that ESCO1 may play an important role in human bladder cancer, and ESCO1 might serve as a novel target and prognosis factor for human bladder cancer. PMID- 26547587 TI - DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin. AB - Decorin (DCN), as an important component of the extracellular matrix (ECM), is a small leucine-rich proteoglycan and synthesized by fibroblasts. Although DCN is dysregulated in numerous cancer types, limited data are available on the expression level and important role of DCN proteins in renal cell carcinoma (RCC). In our study, we examined the expression patterns of DCN messenger RNA (mRNA) in RCCs through the Oncomine database and DCN protein in 94 RCC specimens by immunohistochemistry (IHC). The results revealed that DCN expression was decreased in cancerous tissues compared to adjacent noncancerous tissues and was highly correlated to tumor size. Then, via gain-of-function analyses, DCN overexpression could inhibit RCC cell proliferation and metastasis in vitro and vivo. At the mechanism level, we found that an ectopic expression of DCN significantly upregulated P21 and E-cadherin expression. Altogether, these results revealed that DCN is a tumor suppressor in RCC, and it could serve as a potential therapeutic target in patients with RCC. PMID- 26547588 TI - Characterization of condensed tannins and carbohydrates in hot water bark extracts of European softwood species. AB - Condensed tannins extracted from European softwood bark are recognized as alternatives to synthetic phenolics. The extraction is generally performed in hot water, leading to simultaneous extraction of other bark constituents such as carbohydrates, phenolic monomers and salts. Characterization of the extract's composition and identification of the extracted tannins' molecular structure are needed to better identify potential applications. Bark from Silver fir (Abies alba [Mill.]), European larch (Larix decidua [Mill.]), Norway spruce (Picea abies [Karst.]), Douglas fir (Pseudotsuga menziesii [Mirb.]) and Scots pine (Pinus sylvestris [L.]) were extracted in water at 60 degrees C. The amounts of phenolic monomers, condensed tannins, carbohydrates, and inorganic compounds in the extract were determined. The molecular structures of condensed tannins and carbohydrates were also investigated (HPLC-UV combined with thiolysis, MALDI-TOF mass spectrometry, anion exchange chromatography). Distinct extract compositions and tannin structures were found in each of the analysed species. Procyanidins were the most ubiquitous tannins. The presence of phenolic glucosides in the tannin oligomers was suggested. Polysaccharides such as arabinans, arabinogalactans and glucans represented an important fraction of all extracts. Compared to traditionally used species (Mimosa and Quebracho) higher viscosities as well as faster chemical reactivities are expected in the analysed species. The most promising species for a bark tannin extraction was found to be larch, while the least encouraging results were detected in pine. A better knowledge of the interaction between the various extracted compounds is deemed an important matter for investigation in the context of industrial applications of such extracts. PMID- 26547589 TI - Plasma Neprilysin Concentrations: A New Prognostic Marker in Heart Failure? PMID- 26547590 TI - Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis. AB - BACKGROUND: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. PMID- 26547593 TI - Ask someone who cares: Caregiver surveys as a means of improving the management of pancreatic cancer patients. PMID- 26547592 TI - Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial. AB - OBJECTIVE: Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 MUg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23. PMID- 26547591 TI - CFTR potentiator therapy ameliorates impaired insulin secretion in CF patients with a gating mutation. AB - OBJECTIVE: To investigate the effect of treatment with ivacaftor on insulin secretion in patients with cystic fibrosis (CF) (DeltaF508?S549R) having CFRD/impaired insulin secretion. METHODS: A standard OGTT was performed before and after 16weeks of treatment with ivacaftor in 2 sibling patients with CF carrying the S549R gating mutation. The area under the curve (AUC) for glucose and insulin was calculated using the trapezoidal estimation. RESULTS: Before treatment, the OGTT of case 1 showed indeterminate glycemia; the OGTT of case 2 indicated CFRD. After ivacaftor treatment the OGTT demonstrated improved insulin secretion pattern mainly by increased first phase early insulin secretion, resulting in reduction of the AUC of glucose in both cases. CONCLUSIONS: The treatment with ivacaftor in patients with CF carrying gating mutation can ameliorate impaired insulin secretion. Further studies and larger cohorts are needed to evaluate the impact of ivacaftor on insulin secretion in patients with CF carrying gating or other mutations. PMID- 26547594 TI - Role of pharmacist-provided point of care testing. PMID- 26547595 TI - Optimizing finite resources: Pharmacist chart reviews in an outpatient kidney transplant clinic. AB - OBJECTIVE: To determine if a pharmacist-executed comprehensive chart review could serve as sufficient substitution for direct participation during outpatient clinic visits in the postdischarge follow-up treatment of kidney transplant recipients. DESIGN: Retrospective, longitudinal, cross-sectional study. SETTING: Acute and chronic transplant clinics at the Medical University of South Carolina, Charleston, SC. PARTICIPANTS: 219 individual kidney transplant recipients. MAIN OUTCOME MEASURES: Effectiveness of chart review assessments (with written notes) as compared with in-clinic assessments (with verbal communication with transplant providers followed by documentation by pharmacists). An independent transplant provider graded pharmacist recommendations by severity. All recommendations were compared with the provider's plan to determine if the recommendations were incorporated. RESULTS: During the 3-month study period, 170 pharmacist chart reviews were written and 175 clinic visits involved direct pharmacist participation. Providers accepted a greater percentage of recommendations that were delivered directly compared with recommendations presented via a note in the patient folder following chart review (92% vs. 28%, respectively; P <0.0001). Directly provided recommendations were also associated with higher severity scores. CONCLUSION: The results of this study suggest that comprehensive chart review by pharmacists prior to patient clinic visits may not be as effective as in-person consultation in communicating recommendations to providers. Further research is needed in similar clinic settings. PMID- 26547596 TI - Check it out: A practical tool for improving medication safety. AB - OBJECTIVE: To recommend incorporation of a prospective drug utilization review (DUR) checklist into the routine processing of prescription orders in the community practice setting to improve the quality and safety of pharmaceutical care. PRACTICE INNOVATION: We proposed a checklist that was designed to include all the elements of a prospective DUR required by the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) and most pharmacy practice acts. CONCLUSION: If properly incorporated into workflow and supported by company policies and procedures, a simple DUR checklist like that proposed in this study could significantly improve the quality of pharmacists' prospective DUR activities and the safety of medication therapy provided to patients. We also recommend that future quality metrics be created and implemented to ensure that pharmacists consistently perform this key professional responsibility. PMID- 26547597 TI - User testing and performance evaluation of the Electronic Quality Improvement Platform for Plans and Pharmacies. AB - OBJECTIVE: To user-test and evaluate a performance information management platform that makes standardized, benchmarked medication use quality data available to both health plans and community pharmacy organizations. SETTING: Multiple health/drug plans and multiple chain and independent pharmacies across the United States. EVALUATION: During the first phase of the study, user experience was measured via user satisfaction surveys and interviews with key personnel (pharmacists, pharmacy leaders, and health plan leadership). Improvements were subsequently made to the platform based on these findings. During the second phase of the study, the platform was implemented in a greater number of pharmacies and by a greater number of payers. User experience was then reevaluated to gather information for further improvements. RESULTS: The surveys and interviews revealed that users found the Web-based platform easy to use and beneficial in terms of understanding and comparing performance metrics. Primary concerns included lack of access to real-time data and patient-specific data. Many users also expressed uncertainty as to how they could use the information and data provided by the platform. CONCLUSION: The study findings indicate that while information management platforms can be used effectively in both pharmacy and health plan settings, future development is needed to ensure that the provided data can be transferred to pharmacy best practices and improved quality care. PMID- 26547598 TI - Community pharmacist participation in a practice-based research network: a report from the Medication Safety Research Network of Indiana (Rx-SafeNet). AB - OBJECTIVE: To describe the experiences and opinions of pharmacists serving as site coordinators for the Medication Safety Research Network of Indiana (Rx SafeNet). SETTING: Retail chain, independent, and hospital/health system outpatient community pharmacies throughout Indiana, with a total of 127 pharmacy members represented by 26 site coordinators. PRACTICE DESCRIPTION: Rx-SafeNet, a statewide practice-based research network (PBRN) formed in 2010 and administered by the Purdue University College of Pharmacy. MAIN OUTCOME MEASURES: Barriers and facilitators to participation in available research studies, confidence participating in research, and satisfaction with overall network communication. RESULTS: 22 of 26 site coordinators participated, resulting in an 85% response rate. Most (72.2%) of the respondents had received a doctor of pharmacy degree, and 13.6% had postgraduate year (PGY)1 residency training. The highest reported benefits of PBRN membership were an enhanced relationship with the Purdue University College of Pharmacy (81% agreed or strongly agreed) and enhanced professional development (80% agreed or strongly agreed). Time constraints were identified as the greatest potential barrier to network participation, reported by 62% of respondents. In addition, the majority (59%) of survey respondents identified no prior research experience. Last, respondents' confidence in performing research appeared to increase substantially after becoming network members, with 43% reporting a lack of confidence in engaging in research before joining the network compared with 90% reporting confidence after joining the network. CONCLUSION: In general, Rx-SafeNet site coordinators appeared to experience increased confidence in research engagement after joining the network. While respondents identified a number of benefits associated with network participation, concerns about potential time constraints remained a key barrier to participation. These findings will assist network leadership in identifying opportunities to positively increase member participation in the future. PMID- 26547599 TI - Development and evaluation of a multidisciplinary controlled substances committee within a patient-centered medical home. AB - OBJECTIVE: To present the development of a multidisciplinary controlled substances committee and describe its effectiveness in relation to prescribers' acceptance of committee recommendations, the number of premature deaths associated with controlled substances, and prescribers' need for education on controlled substances. SETTING: A patient-centered medical home and accountable care organization in Maine that serves more than 60,000 patients across a large rural area, 70% of whom are classified as lower income. PRACTICE DESCRIPTION: A multidisciplinary group of prescribers and PharmD residents created a committee to influence organizational culture regarding controlled substances. The Controlled Substances Initiative Committee (CSIC) updated institutional policies, developed provider education, and made personalized patient recommendations to prescribers. MAIN OUTCOME MEASURES: The primary outcome was average change in daily morphine equivalent dose (MED) in patients for whom CSIC recommended a dose reduction to the patient's prescriber. Secondary outcomes included the proportion of patients who died of a known overdose or suspected drug-related death during 2012-2013 or 2013-2014. In addition, prescriber beliefs about controlled substances were measured via a needs assessment. RESULTS: The average daily MED for patients whom CSIC recommended dose reduction was lower after 3 months compared with at baseline (175.5 +/- 344.3 mg vs. 292.7 +/- 466.5 mg; P <0.05). The proportion of patients who died of a known overdose did not differ between 2012-2013 and 2013-2014 (11.8% vs. 11.1%; P = 1.00). However, a greater number of patients had a suspected drug-related death during 2013-2014 compared with during 2012-2013 (0% vs. 27.3%; P = 0.05). CONCLUSION: A multidisciplinary controlled substances committee may improve patient safety and outcomes by offering prescriber support and helping alter prescribing culture. PMID- 26547600 TI - Establishing pathways for access to pharmacist-provided patient care. AB - OBJECTIVE: To describe the pathways being established for access to pharmacist provided patient care and supply recommendations for the next steps in this process. DATA SOURCES: A series of reports published by the American Pharmacists Association regarding pharmacist-provided patient care services. SUMMARY: Community pharmacies and integrated health organizations have emerged as the two predominant pathways for patient access to pharmacist-provided patient care. We view these two pathways as complementary in helping cover patients' entire medication therapy needs as they traverse acute and chronic health care services. However, gaps in access to pharmacist-provided care remain, especially during transitions in care. CONCLUSION: In further establishing pathways for access to pharmacist-provided patient care, we propose that the application of collaboration theory will help close gaps that currently exist between health care organizations. Such an approach carries risk and will require trust among participating organizations. This approach is also likely to require updating and contemporizing pharmacy practice acts and other statutes to allow pharmacists to practice at maximum capacity within new models of care. To perform their new roles and create sustainable business models to support these new functions, pharmacists will need to be paid for their services. To this end, changes will need to be made to payment and documentation systems, incentives, and contracting approaches to develop proper reimbursement and accounting for pharmacists' new roles. PMID- 26547601 TI - HPV9: Combating HPV-associated cancers by strengthening serotype defenses. PMID- 26547602 TI - Sacubitril/valsartan, ivabradine hydrochloride, alirocumab, and evolocumab. PMID- 26547603 TI - Trying to bring common sense to the Common Rule1. PMID- 26547604 TI - Quality of life in South African Black women with alopecia: a pilot study. AB - BACKGROUND: Alopecia has been shown to have a significant impact on quality of life (QoL), particularly in women. However, there are no data for African populations. This study was conducted to pilot an original questionnaire and a model-based methodology to measure QoL and its determinants in a sample of South African Black women of African ancestry with alopecia. METHODS: Fifty participants aged 21-79 years were randomly chosen from patients presenting to dermatologists with alopecia. We used an original questionnaire consisting of 24 items grouped into those assessing the respective impacts of subjective symptoms, objective signs, and relationship issues, measured on a four-level scale. These were then combined using component-based structural equation modeling to return a QoL index (QLI) and to rank the factors contributing to this. RESULTS: On a scale ranging from 0 (high QoL) to 100 (severely decreased QoL), we found a mean QLI of 67.7. The negative impact of alopecia on QoL was higher in younger patients than older patients. The factors with the highest impact were those relating to the subjective experience of alopecia and self-image (56.3%), followed by those relevant to relationships and interaction with other people (34.8%). The presence of objective symptoms and signs such as pruritus was of minor importance (8.9%). CONCLUSIONS: Although not a life-threatening condition, alopecia may seriously impair QoL, particularly by inducing anxiety and reducing self-esteem among African women. Healthcare practitioners should be mindful of this and intervene appropriately to mitigate these effects. PMID- 26547605 TI - [Not Available]. PMID- 26547606 TI - Occurrence Frequencies of Acoustic Patterns of Vocal Fry in American English Speakers. AB - OBJECTIVE: The goal of this study was to analyze the occurrence frequencies of three individual acoustic patterns (A, B, C) and of vocal fry overall (A + B + C) as a function of gender, word position in the sentence (Not Last Word vs. Last Word), and sentence length (number of words in a sentence). STUDY DESIGN: This is an experimental design. METHODS: Twenty-five male and 29 female American English (AE) speakers read the Grandfather Passage. The recordings were processed by a Matlab toolbox designed for the analysis and detection of creaky segments, automatically identified using the Kane-Drugman algorithm. The experiment produced subsamples of outcomes, three that reflect a single, discrete acoustic pattern (A, B, or C) and the fourth that reflects the occurrence frequency counts of Vocal Fry Overall without regard to any specific pattern. Zero-truncated Poisson regression analyses were conducted with Gender and Word Position as predictors and Sentence Length as a covariate. RESULTS: The results of the present study showed that the occurrence frequencies of the three acoustic patterns and vocal fry overall (A + B + C) are greatest at the end of sentences but are unaffected by sentence length. The findings also reveal that AE female speakers exhibit Pattern C significantly more frequently than Pattern B, and the converse holds for AE male speakers. CONCLUSIONS: Future studies are needed to confirm such outcomes, assess the perceptual salience of these acoustic patterns, and determine the physiological correlates of these acoustic patterns. The findings have implications for the design of new excitation models of vocal fry. PMID- 26547607 TI - Voice Disorders: Etiology and Diagnosis. AB - OBJECTIVES: Voice disorders affect adults and children and have different causes in different age groups. The aim of the study is to present the etiology and diagnosis dysphonia in a large population of patients with this voice disorder.for dysphonia of a large population of dysphonic patients. METHODS: We evaluated 2019 patients with dysphonia who attended the Voice Disease ambulatories of a university hospital. Parameters assessed were age, gender, profession, associated symptoms, smoking, and videolaryngoscopy diagnoses. RESULTS: Of the 2019 patients with dysphonia who were included in this study, 786 were male (38.93%) and 1233 were female (61.07). The age groups were as follows: 1-6 years (n = 100); 7-12 years (n = 187); 13-18 years (n = 92); 19-39 years (n = 494); 41-60 years (n = 811); and >60 years (n = 335). Symptoms associated with dysphonia were vocal overuse (n = 677), gastroesophageal symptoms (n = 535), and nasosinusal symptoms (n = 497). The predominant professions of the patients were domestic workers, students, and teachers. Smoking was reported by 13.6% patients. With regard to the etiology of dysphonia, in children (1-18 years old), nodules (n = 225; 59.3%), cysts (n = 39; 10.3%), and acute laryngitis (n = 26; 6.8%) prevailed. In adults (19-60 years old), functional dysphonia (n = 268; 20.5%), acid laryngitis (n = 164; 12.5%), and vocal polyps (n = 156; 12%) predominated. In patients older than 60 years, presbyphonia (n = 89; 26.5%), functional dysphonia (n = 59; 17.6%), and Reinke's edema (n = 48; 14%) predominated. CONCLUSIONS: In this population of 2019 patients with dysphonia, adults and women were predominant. Dysphonia had different etiologies in the age groups studied. Nodules and cysts were predominant in children, functional dysphonia and reflux in adults, and presbyphonia and Reinke's edema in the elderly. PMID- 26547608 TI - [Acute pancreatitis associated with the intragastric balloon]. PMID- 26547609 TI - Endoscopic resection as a treatment for duodenal gangliocytic paraganglioma. PMID- 26547610 TI - A case of sclerosing angiomatoid nodular transformation of the spleen: Imaging and histopathological findings. PMID- 26547611 TI - Primary hepatic lymphoma: An infrequent focal liver tumour. PMID- 26547612 TI - Pneumatosis intestinalis due to 5-fluorouracil chemotherapy. PMID- 26547613 TI - [Treatment of non-cirrhotic, non-tumoural portal vein thrombosis]. AB - Thrombosis of the splenoportal axis not associated with liver cirrhosis or neoplasms is a rare disease whose prevalence ranges from 0.7 to 3.7 per 100,000 inhabitants. However, this entity is the second most common cause of portal hypertension. Prothrombotic factors are present as an underlying cause in up to 70% of patients and local factors in 10-50%. The coexistence of several etiological factors is frequent. Clinical presentation may be acute or chronic (portal cavernomatosis). The acute phase can present as abdominal pain, nausea, vomiting, fever, rectorrhagia, intestinal congestion, and ischemia. In this phase, early initiation of anticoagulation is essential to achieve portal vein recanalization and thus improve patient prognosis. In the chronic phase, symptoms are due to portal hypertension syndrome. In this phase, the aim of treatment is to treat or prevent the complications of portal hypertension. Anticoagulation is reserved to patients with a proven underlying thrombophilic factor. PMID- 26547614 TI - [Treatment of hepatitis C before and after liver transplantation]. AB - Hepatitis C recurrence after liver transplantation is universal and increases morbidity and mortality in these patients. The development of new direct antiviral agents against the hepatitis C virus is a major treatment advance. Pre transplant treatment avoids graft infection and sometimes improves liver function, allowing the patient to be withdrawn from the transplant waiting list. Delaying treatment until the postpostransplant period may be advisable in patients with advanced cirrhosis. Generally, antiviral therapy after liver transplantation is provided in patients with histological evidence of the disease. In these patients, treatment is more effective in the initial stages of the disease. The choice of antiviral therapy in these patients is based on the degree of liver function, the presence of renal failure, and potential drug-drug interactions. PMID- 26547615 TI - Colorectal cancer screening in the familial risk population: Is colonoscopy still the strategy of choice? AB - First-degree relatives of patients with colorectal cancer (CRC) are at high risk of this disease. For this reason, medical organizations and clinical guidelines recommend more intensive screening and surveillance for such first-degree relatives than for the average-risk population. Colonoscopy has been the cornerstone of CRC screening in this setting. Although colonoscopy is the most sensitive technique for the detection of neoplastic lesions (especially non advanced adenomas), its role is less clear for CRC. In addition, screening colonoscopy has several limitations that may affect the success of a screening campaign, such as poor participant acceptance, the need for skilled endoscopists, participant access to screening colonoscopy, overburdened endoscopy units, potential complications, and procedure-related costs. In addition, recent evidence has cast doubt on the advantage of colonoscopy over other strategies for the detection of advanced neoplastic lesions. Despite being less sensitive in general, other screening methods frequently recommended in the average-risk population may be more acceptable and thus help increase CRC screening uptake. This review discusses recent evidence on the risk of CRC in first-degree relatives, the advantages and disadvantages of each screening technique, participation rates depending on the technique, patient preferences, and barriers to screening. PMID- 26547616 TI - Lichen planus after rabies vaccination. PMID- 26547617 TI - Atmospheric metallic and arsenic pollution at an offshore drilling platform in the Bo Sea: A health risk assessment for the workers. AB - To investigate the ambient metal pollution at the offshore drilling platform in the Bo Sea, which few studies have focused on, PM2.5 samples were collected and ten heavy metals, as well as As, were analyzed. High concentration levels of metals were observed, and the heavy metal pollution was quite serious compared to air quality standards and other marine areas. Back trajectories and wind dependent and PCA analyses showed that the marine sources included ship traffic emissions and corrosive stainless steels from the equipment at the platform as well as industrial emissions from stainless steel production and coal combustion sources, which were transported from the surrounding mainland. Both contributed greatly to the ambient metallic particles at the offshore platform. The Hazard Index values of the metals, which were much less than 1, the Carcinogenic Risk data, which were lower than the EPA's acceptable range, and the fact that the metal concentrations did not the exceed the permissible exposure limits of OSHA, indicated that the health risks from the ambient metallic particles for the oil drilling workers were not significant. PMID- 26547618 TI - A simple electrochemical biosensor based on AuNPs/MPS/Au electrode sensing layer for monitoring carbamate pesticides in real samples. AB - A simple electrochemical biosensor for quantitative determination of carbamate pesticide was developed based on a sensing interface of citrate-capped gold nanoparticles (AuNPs)/(3-mercaptopropyl)-trimethoxysilane (MPS)/gold electrode (Au). The biosensor was fabricated by firstly assembling three-dimensional (3D) MPS networks on Au electrode and subsequently assembling citrate-capped AuNPs on 3D MPS network via AuS bond. The interface of AuNPs/MPS/Au was negatively charged originating from the citrate coated on AuNPs that would repulse the negatively charged ferricyanide ([Fe(CN)6](3-/4-)) to produce a negative response. In the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCl), the AChE catalyzes the hydrolysis of ATCl into positively charged thiocholine which would replace the citrate on AuNPs through the strong AuS bond and convert the negative charged surface to be positively charged. The resulted positively charged AuNPs/MPS/Au then attracted the [Fe(CN)6](3-/4-) to produce a positive response. Based on the inhibition of carbamate pesticides on the activity of AChE, the pesticide could be quantitatively determined at a very low potential. The linear range was from 0.003 to 2.00 MUM. The sensing platform was also proved to be suitable for carbamate pesticides detection in practical sample. PMID- 26547619 TI - Arsenate sorption on monohydrocalcite by coprecipitation during transformation to aragonite. AB - The metastability of monohydrocalcite (CaCO3.H2O: MHC) suggests high reactivity to dissolved trace elements. Using kinetic and isotherm sorption experiments with different reaction times (24h, 48h), As(V) sorption on MHC was examined to elucidate As(V) uptake by MHC. Although the MHC was transformed to aragonite with time, the MHC in higher As(V) loading conditions was able to persist longer than in lower loading conditions. Actually, As(V) uptake was negligible for samples in which the MHC remained. However, remarkable uptake of As(V) was observed for samples in which a complete transformation of MHC to aragonite occurred. Results of kinetic study confirmed that the timing of the MHC transformation coincided perfectly with that of As(V) removal from the solution. XAFS measurements showed that the local structure of As after the MHC transformation was almost identical to that of As in the As(V) coprecipitated aragonite. Sorption behavior of As(V) during the transformation is explainable theoretically by the substitution of As(V) into the aragonite structure. The distribution coefficient and (apparent) maximum sorption capacity of As(V) sorption on MHC after 48h at low-to-moderate As(V) concentrations are 500L/kg and 25MUmol/g, respectively, which are much higher than those of simple adsorption of As(V) on calcite. PMID- 26547620 TI - Synergistic effect using vermiculite as media with a bacterial biofilm of Arthrobacter sp. for biodegradation of di-(2-ethylhexyl) phthalate. AB - Vermiculite is one of matrix material used for constructed wetland (CW) for the treatment of municipal wastewater. Arthrobacter sp. strain C21 (CGMCC No. 7671), isolated from a constructed wetland receiving municipal wastewater, forms biofilm on the surface of vermiculite. Di-(2-ethylhexyl) phthalate (DEHP), a typical phthalate pollutant in environment, can be degraded by the biofilm of strain C21 formed on vermiculite. Results of laboratory studies indicated that DEHP was removed from aqueous phase via biodegradation, adsorption by vermiculite, and adsorption by biofilm biomass. Synergistic effect of these three reactions enhanced the overall DEHP removal efficiency. During a batch incubation test with vermiculite and the cell suspension, bacterial adhesion to the media surface occurred within 5h and the phthalate esters (PEs) removal was due to both biodegradation and vermiculite adsorption. As the biofilm developed on surface of vermiculite (5-36 h), biodegradation became the predominance for PEs removal. As mature biofilm was formed (36-54 h), the adsorption of PEs by biofilm biomass became a main driving force for the removal of PEs from aqueous phase. The content of extracellular polymers (EPS) of the biofilm and DEHP removal performance showed a significant positive correlation (rp>0.86). PMID- 26547621 TI - Superoxide radical-mediated photocatalytic oxidation of phenolic compounds over Ag+/TiO2: Influence of electron donating and withdrawing substituents. AB - A comparative study was constructed to correlate the electronic property of the substituents with the degradation rates of phenolic compounds and their oxidation pathways under UV with Ag(+)/TiO2 suspensions. It was verified that a weak electron withdrawing substituent benefited photocatalytic oxidation the most, while an adverse impact appeared when a substituent was present with stronger electron donating or withdrawing ability. The addition of p-benzoquinone dramatically blocked the degradation, confirming superoxide radicals (O2(-)) as the dominant photooxidant, rather than hydroxyl radicals, singlet oxygen or positive holes, which was also independent of the substituent. Hammett relationship was established based on pseudo-first-order reaction kinetics, and it revealed two disparate reaction patterns between O2(-) and phenolic compounds, which was further verified by the quantum chemical computation on the frontier molecular orbitals and Mulliken charge distributions of O2(-) and phenolic compounds. It was found that electron donating group (EDG) substituted phenols were more likely nucleophilically attacked by O2(-), while O2(-) preferred to electrophilically assault electron withdrawing group (EWG) substituted phenols. Exceptionally, electrophilic and nucleophilic attack by O2(-) could simultaneously occur in p-chlorophenol degradation, consequently leading to its highest rate constant. Possible reactive positions on the phenolic compounds were also detailedly uncovered. PMID- 26547622 TI - Explosions of ammonium nitrate fertilizer in storage or transportation are preventable accidents. AB - Ammonium nitrate (AN) is a detonable substance which has led to numerous disasters throughout the 20th century and until the present day, with the latest disaster occurring on 17 April 2013. Needed safety lesson have not been learned, since typically each accident was viewed as a great surprise and investigations focused on finding some unique reason for the accident, rather than examining what is common among the accidents. A review is made of accidents which involved AN for fertilizer purposes, and excluding incidents involving ANFO or additional explosives apart from AN. It is found that, for explosions in storage or transportation, 100% of these disasters had a single causative factor-an uncontrollable fire. Thus, such disasters can be eliminated by eliminating the potential for uncontrolled fire. Two actions are required to achieve this: (1) adoption of fertilizer formulations which reduce the potential for uncontrolled fire and for detonation; and (2) adoption of building safety measures which provide assurance against uncontrolled fires. Technical means are available for achieving both these required measures. These measures have been known for a long time and the only reason that disasters continue to occur is that these safety measures are not implemented. The problem can be solved unilaterally by product manufacturers or by government authorities, but preferably both should take necessary steps. PMID- 26547623 TI - Experimental studies of thermal environment and contaminant transport in a commercial aircraft cabin with gaspers on. AB - Gaspers installed in commercial airliner cabins are used to improve passengers' thermal comfort. To understand the impact of gasper airflow on the air quality in a cabin, this investigation measured the distributions of air velocity, air temperature, and gaseous contaminant concentration in five rows of the economy class section of an MD-82 commercial aircraft. The gaseous contaminant was simulated using SF6 as a tracer gas with the source located at the mouth of a seated manikin close to the aisle. Two-fifths of the gaspers next to the aisle were turned on in the cabin, and each of them supplied air at a flow rate of 0.66 l/s. The airflow rate in the economy-class cabin was controlled at 10 l/s per passenger. Data obtained in a previous study of the cabin with all gaspers turned off were used for comparison. The results show that the jets from the gaspers had a substantial impact on the air velocity and contaminant transport in the cabin. The air velocity in the cabin was higher, and the air temperature slightly more uniform, when the gaspers were on than when they were off, but turning on the gaspers may not have improved the air quality. PMID- 26547625 TI - Collecting and Pooling Assessment and Outcome Data in Couple and Family Therapy Training Clinics: Reasons to Do It, Common Problems, and Some Suggestions for Avoiding Them. AB - The article by Johnson et al. (2015) is an excellent example of many of the advantages and challenges of collecting data in clinics associated with Couple and Family Therapy training programs. In the hopes of encouraging more use of clinic datasets for research, we suggest some ways to improve the feasibility, quality, and value of routinely collecting such data. PMID- 26547624 TI - The Liver Clock Controls Cholesterol Homeostasis through Trib1 Protein-mediated Regulation of PCSK9/Low Density Lipoprotein Receptor (LDLR) Axis. AB - Disruption of the body clock has been recognized as a risk factor for cardiovascular disease. How the circadian pacemaker interacts with the genetic factors associated with plasma lipid traits remains poorly understood. Recent genome-wide association studies have identified an expanding list of genetic variants that influence plasma cholesterol and triglyceride levels. Here we analyzed circadian regulation of lipid-associated candidate genes in the liver and identified two distinct groups exhibiting rhythmic and non-rhythmic patterns of expression during light-dark cycles. Liver-specific inactivation of Bmal1 led to elevated plasma LDL/VLDL cholesterol levels as a consequence of the disruption of the PCSK9/LDL receptor regulatory axis. Ablation of the liver clock perturbed diurnal regulation of lipid-associated genes in the liver and markedly reduced the expression of the non-rhythmically expressed gene Trib1. Adenovirus-mediated rescue of Trib1 expression lowered plasma PCSK9 levels, increased LDL receptor protein expression, and restored plasma cholesterol homeostasis in mice lacking a functional liver clock. These results illustrate an unexpected mechanism through which the biological clock regulates cholesterol homeostasis through its regulation of non-rhythmic genes in the liver. PMID- 26547626 TI - Reply. PMID- 26547627 TI - A novel c.2T>A NDP missense mutation in a Chinese family with Norrie disease. PMID- 26547628 TI - The PDGF system and its antagonists in liver fibrosis. AB - Platelet derived growth factor (PDGF) signaling plays an important role in activated hepatic stellate cells and portal fibroblast proliferation, chemotaxis, migration and cell survival. PDGF receptors and ligands are upregulated in experimental liver fibrotic models as well as in human liver fibrotic diseases. Blocking of PDGF signaling ameliorates experimental liver fibrogenesis. The plurality of molecular and cellular activities of PDGF and its involvement in initiation, progression and resolution of hepatic fibrogenesis offers an infinite number of therapeutic possibilities. These include the application of therapeutic antibodies (e.g. AbyD3263, MOR8457) which specifically sequester individual PDGF isoforms or the inhibition of PDGF isoforms by synthetic aptamers. In particular, the isolation of innovative slow off-rate modified aptamers (e.g., SOMAmer SL1 and SL5) that carry functional groups absent in natural nucleic acids by the Systematic Evolution of Ligands by EXponential (SELEX) enrichment technique offers the possibility to design high affinity aptamers that target PDGF isoforms for clinical purposes. Dominant-negative soluble PDGF receptors are also effective in attenuation of hepatic stellate cell proliferation and hepatic fibrogenesis. Moreover, some multikinase inhibitors targeting PDGF signaling have been intensively tested during the last decade and are on the way into advanced preclinical studies and clinical trials. This narrative review aims to gauge the recent progression of research into PDGF systems and liver fibrosis. PMID- 26547630 TI - Evolution of sickle cell disease from a life-threatening disease of children to a chronic disease of adults: The last 40 years. AB - Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries. PMID- 26547629 TI - A population-based estimate of the economic burden of influenza in Peru, 2009 2010. AB - INTRODUCTION: Influenza disease burden and economic impact data are needed to assess the potential value of interventions. Such information is limited from resource-limited settings. We therefore studied the cost of influenza in Peru. METHODS: We used data collected during June 2009-December 2010 from laboratory confirmed influenza cases identified through a household cohort in Peru. We determined the self-reported direct and indirect costs of self-treatment, outpatient care, emergency ward care, and hospitalizations through standardized questionnaires. We recorded costs accrued 15-day from illness onset. Direct costs represented medication, consultation, diagnostic fees, and health-related expenses such as transportation and phone calls. Indirect costs represented lost productivity during days of illness by both cases and caregivers. We estimated the annual economic cost and the impact of a case of influenza on a household. RESULTS: There were 1321 confirmed influenza cases, of which 47% sought health care. Participants with confirmed influenza illness paid a median of $13 [interquartile range (IQR) 5-26] for self-treatment, $19 (IQR 9-34) for ambulatory non-medical attended illness, $29 (IQR 14-51) for ambulatory medical attended illness, and $171 (IQR 113-258) for hospitalizations. Overall, the projected national cost of an influenza illness was $83-$85 millions. Costs per influenza illness represented 14% of the monthly household income of the lowest income quartile (compared to 3% of the highest quartile). CONCLUSION: Influenza virus infection causes an important economic burden, particularly among the poorest families and those hospitalized. Prevention strategies such as annual influenza vaccination program targeting SAGE population at risk could reduce the overall economic impact of seasonal influenza. PMID- 26547631 TI - Tonically active NMDA receptors--a signalling mechanism critical for interneuronal excitability in the CA1 stratum radiatum. AB - In contrast to tonic extrasynaptic gamma-aminobutyric acid (GABA)A receptor mediated signalling, the physiological significance of tonic extrasynaptic N methyl-D-aspartate (NMDA) receptor (NMDAR)-mediated signalling remains uncertain. In this study, reversible open-channel blockers of NMDARs, memantine and phencyclidine (PCP) were used as tools to examine tonic NMDAR-mediated signalling in rat hippocampal slices. Memantine in concentrations up to 10 MUM had no effect on synaptically evoked NMDAR-mediated responses in pyramidal neurons or GABAergic interneurons. On the other hand, 10 MUM memantine reduced tonic NMDAR-mediated currents in GABAergic interneurons by approximately 50%. These tonic NMDAR mediated currents in interneurons contributed significantly to the excitability of the interneurons as 10 MUM memantine reduced the disynaptic inhibitory postsynaptic current in pyramidal cells by about 50%. Moreover, 10 MUM memantine, but also PCP in concentrations <= 1 MUM, increased the magnitude of the population spike, likely because of disinhibition. The relatively higher impact of tonic NMDAR-mediated signalling in interneurons was at least partly explained by the expression of GluN2D-containing NMDARs, which was not observed in mature pyramidal cells. The current results are consistent with the idea that low doses of readily reversible NMDAR open-channel blockers preferentially inhibit tonically active extrasynaptic NMDARs, and they suggest that tonically active NMDARs contribute more prominently to the intrinsic excitation in GABAergic interneurons than in pyramidal cells. It is proposed that this specific difference between interneurons and pyramidal cells can explain the disinhibition caused by the Alzheimer's disease medication memantine. PMID- 26547632 TI - Multiple Endocrine Neoplasia, Type 1: Imaging Solutions to Clinical Questions. AB - The common clinical presentations of multiple endocrine neoplasia, type 1 (MEN1) often lead to predictable clinical questions that can be answered with imaging. From pituitary adenomas to parathyroid adenoms and pancreaticoduodenal neuroendocrine tumors, the multiple faces of MEN1 require an understanding of the basic disease characteristics and an understanding of multiple imaging modalities. We attempt to provide the reader with a basic understanding of the common clinical questions raised by patients with MEN1 and how radiologists can provide critical management information. PMID- 26547633 TI - Trans-Stent B-Mode Ultrasound and Passive Cavitation Imaging. AB - Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis. PMID- 26547635 TI - Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review. AB - Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo- and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold-type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation-induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism-based treatment and improve clinical outcome. PMID- 26547634 TI - Calibration and Evaluation of Ultrasound Thermography Using Infrared Imaging. AB - Real-time monitoring of the spatiotemporal evolution of tissue temperature is important to ensure safe and effective treatment in thermal therapies including hyperthermia and thermal ablation. Ultrasound thermography has been proposed as a non-invasive technique for temperature measurement, and accurate calibration of the temperature-dependent ultrasound signal changes against temperature is required. Here we report a method that uses infrared thermography for calibration and validation of ultrasound thermography. Using phantoms and cardiac tissue specimens subjected to high-intensity focused ultrasound heating, we simultaneously acquired ultrasound and infrared imaging data from the same surface plane of a sample. The commonly used echo time shift-based method was chosen to compute ultrasound thermometry. We first correlated the ultrasound echo time shifts with infrared-measured temperatures for material-dependent calibration and found that the calibration coefficient was positive for fat mimicking phantom (1.49 +/- 0.27) but negative for tissue-mimicking phantom ( 0.59 +/- 0.08) and cardiac tissue (-0.69 +/- 0.18 degrees C-mm/ns). We then obtained the estimation error of the ultrasound thermometry by comparing against the infrared-measured temperature and revealed that the error increased with decreased size of the heated region. Consistent with previous findings, the echo time shifts were no longer linearly dependent on temperature beyond 45 degrees C 50 degrees C in cardiac tissues. Unlike previous studies in which thermocouples or water bath techniques were used to evaluate the performance of ultrasound thermography, our results indicate that high-resolution infrared thermography is a useful tool that can be applied to evaluate and understand the limitations of ultrasound thermography methods. PMID- 26547636 TI - Management of Indigenous patients presenting with non ST-segment elevation acute coronary syndrome in South Australia: a retrospective cohort study. AB - AIM: Using Australian guidelines for management of acute coronary syndromes, we assessed the probability of an Indigenous patient receiving interventional and therapeutic care after presenting in two metropolitan hospitals. METHODS: A retrospective case note review of patients admitted through two Adelaide public tertiary hospital emergency departments from December 2007 to December 2009. The study cohort was 488 patients with high-risk clinical features without ST-segment elevation. RESULTS: Indigenous patients were significantly younger, present later in the disease process and have a higher burden of cardiovascular risk factors when compared with non-Indigenous patients. Indigenous patients were 54% more likely to receive angiography (Risk ratios (RR) = 1.54; 95% CI 1.31; 1.81) than non-Indigenous patients, however, this difference disappeared after adjustment for age, sex and propensity score. Indigenous patients were 20% more likely to receive the recommended medications (RR = 1.19, 95% CI 1.01; 1.40) compared with non-Indigenous patients. Patients over 65 years were 53% less likely to receive an angiogram (RR = 0.47, 95% CI 0.38; 0.56) and were 35% less likely to receive the recommended medications (RR = 0.65, 95% CI 0.54; 0.78) than a patient at the ages of 18-49. Women were almost 20% less likely to receive an angiogram (RR = 0.81, 95% CI 0.66; 0.99) and 20% less likely to receive the recommended medications (RR = 0.80, 95% CI 0.71; 0.91) when compared with men. The likelihood of receiving medications on discharge was significantly influenced by age, gender, ethnicity, comorbid burden and revascularisation. CONCLUSIONS: The younger age and significantly higher-risk profile of Indigenous adults presenting to SA hospitals with acute coronary syndromes appears to lead to different management decisions, which may well be led by patient factors. Many of these risk conditions can be better managed in the primary care setting. PMID- 26547637 TI - Lying times of lactating cows on dairy farms with automatic milking systems and the relation to lameness, leg lesions, and body condition score. AB - Lying down and resting are important for optimal cow health, welfare, and production. In comparison with free stall farms with a milking parlor, farms with automated milking systems (AMS) may place less constraint on how long cows can lie down. However, few studies report lying times on AMS farms. The aims of this study were to describe the variation in lying times of dairy cows in AMS farms and to understand how much of the variation in individual lying times is related to cow-level factors, including lameness, the presence of hock and knee lesions, and body condition score (BCS). We visited 36 farms in Canada (Quebec: n = 10; Ontario: n = 10; British Columbia: n = 4; and Alberta: n = 5), and the United States (Michigan: n = 7). Gait scores, presence of hock and knee lesions, and BCS were recorded for 40 Holstein cows from each herd. Parity and days in milk were retrieved from farm records. Lying time was recorded across 4d using accelerometers (n = 1,377). Multivariable analysis was performed. Of scored cows, 15.1% were lame (i.e., obviously limping; 203 of 1,348 cows). Knee lesions were found in 27.1% (340 of 1,256 cows) and hock lesions were found in 30.8% (421 of 1,366 cows) of the animals. Daily lying time varied among cows. Cows spent a median duration of 11.4 h/d lying down (25th-75th percentile = 9.7-12.9 h), with a lying bout frequency of 9.5 bouts/d (25th-75th percentile = 7.5-12 bouts/d) and a median bout duration of 71 min (25th-75th percentile = 58-87 min/bout). Lameness was associated with cows lying down for 0.6 h/d longer in fewer, longer bouts. Increased lying time was also associated with increased parity, later stage of lactation and higher BCS. Older cows (parity >= 3) spent about 0.5 h/d more lying down compared with parity 1 cows, and cows with BCS >= 3.5 lay down on average 1 h/d longer than cows with BCS <= 2.25. Hock lesions were associated with shorter lying times in univariable models, but no associations were found in the multivariable models. We concluded that only a small proportion of the variation between cows in lying time is explained by lameness, leg lesions, and BCS. PMID- 26547638 TI - Dairy farmers' use and non-use values in animal welfare: Determining the empirical content and structure with anchored best-worst scaling. AB - In this study, we sought to identify empirically the types of use and non-use values that motivate dairy farmers in their work relating to animal welfare of dairy cows. We also sought to identify how they prioritize between these use and non-use values. Use values are derived from productivity considerations; non-use values are derived from the wellbeing of the animals, independent of the present or future use the farmer may make of the animal. In particular, we examined the empirical content and structure of the economic value dairy farmers associate with animal welfare of dairy cows. Based on a best-worst scaling approach and data from 123 Swedish dairy farmers, we suggest that the economic value those farmers associate with animal welfare of dairy cows covers aspects of both use and non-use type, with non-use values appearing more important. Using principal component factor analysis, we were able to check unidimensionality of the economic value construct. These findings are useful for understanding why dairy farmers may be interested in considering dairy cow welfare. Such understanding is essential for improving agricultural policy and advice aimed at encouraging dairy farmers to improve animal welfare; communicating to consumers the values under which dairy products are produced; and providing a basis for more realistic assumptions when developing economic models about dairy farmers' behavior. PMID- 26547639 TI - Improving the reliability of female fertility breeding values using type and milk yield traits that predict energy status in Australian Holstein cattle. AB - The objectives of this study were (1) to propose changing the selection criteria trait for evaluating fertility in Australia from calving interval to conception rate at d 42 after the beginning of the mating season and (2) to use type traits as early fertility predictors, to increase the reliability of estimated breeding values for fertility. The breeding goal in Australia is conception within 6 wk of the start of the mating season. Currently, the Australian model to predict fertility breeding values (expressed as a linear transformation of calving interval) is a multitrait model that includes calving interval (CVI), lactation length (LL), calving to first service (CFS), first nonreturn rate (FNRR), and conception rate. However, CVI has a lower genetic correlation with the breeding goal (conception within 6 wk of the start of the mating season) than conception rate. Milk yield, type, and fertility data from 164,318 cow sired by 4,766 bulls were used. Principal component analysis and genetic correlation estimates between type and fertility traits were used to select type traits that could subsequently be used in a multitrait analysis. Angularity, foot angle, and pin set were chosen as type traits to include in an index with the traits that are included in the multitrait fertility model: CVI, LL, CFS, FNRR, and conception rate at d 42 (CR42). An index with these 8 traits is expected to achieve an average bull first proof reliability of 0.60 on the breeding objective (conception within 6 wk of the start of the mating season) compared with reliabilities of 0.39 and 0.45 for CR42 only or the current 5-trait Australian model. Subsequently, we used the first eigenvector of a principal component analysis with udder texture, bone quality, angularity, and body condition score to calculate an energy status indicator trait. The inclusion of the energy status indicator trait composite in a multitrait index with CVI, LL, CFS, FNRR, and CR42 achieved a 12-point increase in fertility breeding value reliability (i.e., increased by 30%; up to 0.72 points of reliability), whereas a lower increase in reliability (4 points, i.e., increased by 10%) was obtained by including angularity, foot angle, and pin set in the index. In situations when a limited number of daughters have been phenotyped for CR42, including type data for sires increased reliabilities compared with when type data were omitted. However, sires with more than 80 daughters with CR42 records achieved reliability estimates close to 80% on average, and there did not appear to be a benefit from having daughters with type records. The cost of phenotyping to obtain such reliabilities (assuming a cost of AU$14 per cow with type data and AU$5 per cow with pregnancy diagnosed) is lower if more pregnancy data are collected in preference to type data. That is, efforts to increase the reliability of fertility EBV are most cost effective when directed at obtaining a larger number of pregnancy tests. PMID- 26547640 TI - Identification and characterization of psychrotolerant coliform bacteria isolated from pasteurized fluid milk. AB - The presence of coliform bacteria in pasteurized fluid milk typically indicates that product contamination occurred downstream of the pasteurizer, but it may also indicate pasteurization failure. Although coliform detection is frequently used as a hygiene indicator for dairy products, our understanding of the taxonomic and phenotypic coliform diversity associated with dairy products is surprisingly limited. Therefore, using Petrifilm Coliform Count plates (3M, St. Paul, MN), we isolated coliforms from high-temperature, short-time (HTST) pasteurized fluid milk samples from 21 fluid milk processing plants in the northeast United States. Based on source information and initial characterization using partial 16S rDNA sequencing, 240 nonredundant isolates were obtained. The majority of these isolates were identified as belonging to the genera Enterobacter (42% of isolates), Hafnia (13%), Citrobacter (12%), Serratia (10%), and Raoultella (9%); additional isolates were classified into the genera Buttiauxella, Cedecea, Kluyvera, Leclercia, Pantoea, and Rahnella. A subset of 104 representative isolates was subsequently characterized phenotypically. Cold growth analysis in skim milk broth showed that all isolates displayed at least a 2-log increase over 10 d at 6 degrees C; the majority of isolates (n=74) displayed more than a 5-log increase. In total, 43% of the representative isolates displayed lipolysis when incubated on spirit blue agar at 6 degrees C for 14 d, whereas 71% of isolates displayed proteolysis when incubated on skim milk agar at 6 degrees C for 14 d. Our data indicate that a considerable diversity of coliforms is found in HTST-pasteurized fluid milk and that a considerable proportion of these coliforms have phenotypic characteristics that will allow them to cause fluid milk spoilage. PMID- 26547641 TI - Genetic parameters between feed-intake-related traits and conformation in 2 separate dairy populations--the Netherlands and United States. AB - To include feed-intake-related traits in the breeding goal, accurate estimates of genetic parameters of feed intake, and its correlations with other related traits (i.e., production, conformation) are required to compare different options. However, the correlations between feed intake and conformation traits can vary depending on the population. Therefore, the objective was to estimate genetic correlations between 6 feed-intake-related traits and 7 conformation traits within dairy cattle from 2 countries, the Netherlands (NL) and the United States (US). The feed-intake-related traits were dry matter intake (DMI), residual feed intake (RFI), milk energy output (MilkE), milk yield (MY), body weight (BW), and metabolic body weight (MBW). The conformation traits were stature (ST), chest width (CW), body depth (BD), angularity (ANG), rump angle (RA), rump width (RW), and body condition score (BCS). Feed intake data were available for 1,665 cows in NL and for 1,920 cows in US, from 83 nutritional experiments (48 in NL and 35 in US) conducted between 1991 and 2011 in NL and between 2007 and 2013 in US. Additional conformation records from relatives of the animals with DMI records were added to the database, giving a total of 37,241 cows in NL and 28,809 in US with conformation trait information. Genetic parameters were estimated using bivariate animal model analyses. The model included the following fixed effects for feed-intake-related traits: location by experiment-ration, age of cow at calving modeled with a second order polynomial by parity class, location by year season, and days in milk, and these fixed effects for the conformation traits: herd by classification date, age of cow at classification, and lactation stage at classification. Both models included additive genetic and residual random effects. The highest estimated genetic correlations involving DMI were with CW in both countries (NL=0.45 and US=0.61), followed by ST (NL=0.33 and US=0.57), BD (NL=0.26 and US=0.49), and BCS (NL=0.24 and US=0.46). The MilkE and MY were moderately correlated with ANG in both countries (0.33 and 0.47 in NL, and 0.36 and 0.48 in US). Finally, BW was highly correlated with CW (0.77 in NL and 0.84 in US) and with BCS (0.83 in NL and 0.85 in US). Feed-intake-related traits were moderately to highly genetically correlated with conformation traits (ST, CW, BD, and BCS) in both countries, making them potentially useful as predictors of DMI. PMID- 26547642 TI - Short communication: Measuring feed volume and weight by machine vision. AB - Individual dairy cow feed intake is closely related to the health and productive output of each cow, with healthy cows generally eating more feed than unhealthy cows. Incorporating the use of an automated system to monitor feed consumption for each cow may be beneficial for dairy farm management. This study examined the use of an inexpensive 3-dimensional video camera to measure feed volume, from which we derived feed weight. Proof-of-concept testing was conducted to determine the effectiveness and capability of the machine vision feed-scanning system and its possible use in feed intake monitoring. Such systems are ideal because they do not impede the workflow of the farm or interrupt feeding behavior. This is an improvement over existing systems that are labor and cost intensive. Our conducted experiments involve measuring feed volume at known weights, up to 22.68 kg, with the resulting volume and weight values analyzed by means of linear and quadratic least squares t-test regression analysis. The effects of feed positioning in the bin and near-range sensor limitations were also examined. The results showed that an estimation of feed weight from 3-dimensional scan of volume measurements could be made to within 0.5 kg of the physically measured feed weight using a digital scale. Future efforts will focus on extending this work to active bunks with multiple cows eating throughout the day and testing total mixed rations of varied composition. PMID- 26547643 TI - Genetic analysis of calving traits by the multi-trait individual animal model. AB - Five alternative models were applied for analysis of dystocia and stillbirth in first and second parities. Models 1 and 2 were included only to estimate the parameters required for model 4, and models 3 and 5 are included only as comparisons to the model 4 estimates. Variance components were estimated by multi trait REML, including cows with valid calving records for both parities. For the effects of sire of calf on first and second parities, variance components were estimated including only calvings with the same sire of calf for both parities. All heritabilities for the cow effect were quite low, but higher for dystocia than for stillbirth and higher in first parity. The sire-of-calf heritabilities were higher than the cow effect heritabilities, except for stillbirth in parity 2. Unlike the effect of cow correlations, all sire of calf correlations were >0.6, and the correlations for the same trait in parities 1 and 2 were >0.9. Thus, a multi-trait analysis should yield a significant gain in accuracy with respect to the sire of calf effects for bulls not mated to virgin heifers. A multi-trait individual animal model algorithm was developed for joint analysis of dystocia and stillbirth in first and second parities. Relationships matrices were included both for the effects of cow and sire of calf. In addition, random herd year-season and fixed sex of calf effects were included in the model. Records were preadjusted for calving month and age. A total of 899,223 Israeli Holstein cows with first calvings since 1985 were included in the complete analysis. Approximate reliabilities were computed for both sire of cow and sire of calf effects. Correlations between these reliabilities and reliabilities obtained by direct inversion of the coefficient matrix for a sire of cow-sire of calf model were all close to 0.99. Phenotypic trends for cows born from 1983 through 2007 were economically unfavorable for dystocia and favorable for stillbirth in both parities. Genetic trends were economically unfavorable for both dystocia and stillbirth in first parity. First-parity sire of calf trends were unfavorable for dystocia, but favorable for stillbirth. All environmental trends were nearly zero. Regressions of evaluations of the complete analysis on a model including only calvings before 2011 were all >0.8. All evaluations met the Interbull Method 3 criterion for unbiasedness. Model 4, which computed genetic evaluations for all animals for all 4 traits accounting for all known relationships and correlations among the traits, is recommended for routine genetic evaluation of calving traits. PMID- 26547644 TI - Survival of the functional yeast Kluyveromyces marxianus B0399 in fermented milk with added sorbic acid. AB - In this study, the survival of the functional yeast Kluyveromyces marxianus B0399 in an industrially produced fermented milk was evaluated. In particular, the yeast viability was assessed throughout the entire shelf-life of the product (30 d) to ensure the presence of the effective yeast dose (20 million viable cells for each serving of 125 g) while avoiding, by sorbic acid addition, yeast growth, which could affect product quality and stability. To find the best combination of yeast and sorbic acid concentration, 13 different combinations were tested, and then 2 of them were chosen for industrial production. In production at lower concentrations (30 million viable cells, 150 mg/kg of sorbic acid) the effective dose was maintained only at 4 and 6 degrees C, whereas at higher dosages (70 million viable cells, 250 mg/kg of sorbic acid) the effect of temperature was less evident. In all the trials, the concentration of sorbic acid was not affected by microbial metabolism and remained stable throughout the entire shelf life. PMID- 26547645 TI - Acidic pH and short-chain fatty acids activate Na+ transport but differentially modulate expression of Na+/H+ exchanger isoforms 1, 2, and 3 in omasal epithelium. AB - Low sodium content in feed and large amounts of salivary sodium secretion are essential requirements to efficient sodium reabsorption in the dairy cow. It is already known that Na(+)/H(+) exchange (NHE) of the ruminal epithelium plays a key role in Na(+) absorption, and its function is influenced by the presence of short-chain fatty acids (SCFA) and mucosal pH. By contrast, the functional role and regulation of NHE in omasal epithelium have not been completely understood. In the present study, we used model studies in small ruminants (sheep and goats) to investigate NHE-mediated Na(+) transport and the effects of pH and SCFA on NHE activity in omasal epithelium and on the expression of NHE isoform in omasal epithelial cells. Conventional Ussing chamber technique, primary cell culture, quantitative PCR, and Western blot were used. In native omasal epithelium of sheep, the Na(+) transport was electroneutral, and it was inhibited by the specific NHE3 inhibitor 3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride, which decreased mucosal-to-serosal, serosal-to-mucosal, and net flux rates of Na(+) by 80% each. The application of low mucosal pH (6.4 or 5.8) in the presence of SCFA activated the Na(+) transport across omasal epithelium of sheep compared with that at pH 7.4. In cultured omasal epithelial cells of goats, mRNA and protein of NHE1, NHE2, and NHE3 were detected. The application of SCFA increased NHE1 mRNA and protein expression, which was most prominent when the culture medium pH decreased from 7.4 to 6.8. At variance, the mRNA and protein expression of NHE2 and NHE3 were decreased with low pH and SCFA, which was contrary to the published data from ruminal epithelial studies. In conclusion, this paper shows that (1) NHE1, NHE2, and NHE3 are expressed in omasal epithelium; (2) NHE3 mediates the major portion of transepithelial Na(+) transport in omasal epithelium; and (3) SCFA and acidic pH acutely activate Na(+) transport but suppress the expression of NHE2 and NHE3 in the longer term. By contrast, the expression of NHE1 is increased by SCFA and acidic pH, indicating a prominent role for NHE1 in the regulation of intracellular pH of omasal epithelium. Our results suggest a regulatable Na(+) absorption in ruminal and omasal epithelium. It is of benefit for intracellular pH homeostasis and highly relevant to dairy cows fed on high-concentrate diets. PMID- 26547646 TI - Localization and quantitation of macrophages, mast cells, and eosinophils in the developing bovine mammary gland. AB - Prepubertal mammary development involves elongation and branching of ducts and stromal tissue remodeling. This process is highly regulated and in mice is known to be affected by the presence of innate immune cells. Whether or not such immune cells are present or involved in bovine mammary development is unknown. For the first time, we determined the presence, location (relative to mammary ductal structures), and changes in numbers of eosinophils, mast cells, and macrophages in prepubertal bovine mammary tissue, and evaluated the effects of age, ovariectomy, and exogenous estrogen on numbers of each cell type. Chemical stains and immunofluorescence were used to identify the 3 cell types in formalin-fixed, paraffin-embedded mammary tissue from prepubertal female calves from 3 archived tissue sets. The ontogeny tissue set included samples of mammary tissue from female calves (n=4/wk) from birth to 6 wk of age. The ovary tissue set contained samples from ovary intact and ovariectomized heifers allowing us to investigate the influence of the ovaries on immune cells in the developing mammary gland in prepubertal heifers. Nineteen animals were intact or ovariectomized 30 d before sampling; they were 90, 120, or 150 d old at the time of sampling. A third tissue set, the estrogen set, allowed us to determine the effect of exogenous estrogen on innate immune cells in the gland. Eosinophils were identified via Luna staining, mast cells by May-Grunwald Giemsa staining, and macrophages with immunofluorescence. Key findings were that more eosinophils and mast cells were observed in near versus far stroma in the ontogeny and ovary tissue sets but not estrogen. More macrophages were observed in near versus far stroma in ontogeny animals. Eosinophils were more abundant in the younger animals, and fewer macrophages tended to be observed in ovariectomized heifers as compared with intact heifers and estrogen treatment resulted in a reduction in cell numbers. In summary, we show for the first time that innate immune cells are present in prepubertal bovine mammary tissue, localization varies by immune cell type, and abundance is related to proximity of epithelial structures and physiological state. We suggest a likely role for these cells in control of bovine mammary growth and ductal development. PMID- 26547647 TI - Short communication: A nanoemulsified form of oil blends positively affects the fatty acid proportion in ruminal batch cultures. AB - Two consecutive rumen batch cultures were used to study the effect of nanoemulsified oils as a new type of supplement, on the in vitro fatty acid proportion and vaccenic acid formation. Three levels (3, 5, and 7%) of 2 different oil blends [soybean:fish oil (SF) or rapeseed-fish oil (RF)] were used. Both oil blends were used either in the raw form (SF or RF, respectively) or in the nanoemulsified form (NSF or NRF, respectively). The diets were the control (0%), which consisted of a dry total mixed ration without any supplements, the control plus 3, 5, or 7% of the SF or RF oil blend in appropriate form (raw or nanoemulsified). For each treatment, 6 incubation vessels were used. Each batch culture was incubated for 24h and conducted twice in 2 consecutive days. All supplements were calculated as a percentage of the substrate dry matter (400mg). Nanoemulsified supplements were recalculated to make sure the oil amount was equal to the raw oil supplementation levels. The results from both experiments indicated that the proportions of vaccenic acid and cis-9,trans-11 C18:2 increased when a raw oil blend was supplemented; on the other hand, no influence of nanoemulsified form of oil blend was observed on the proportion cis-9,trans-11 C18:2. Generally, supplementation with the nanoemulsified oil blends had less effect on biohydrogenation intermediates than the raw form of oil blends. However, the nanoemulsified form had a greater effect on the increase of n-3 and n-6 fatty acids. Nanoemulsified oil blends had a positive effect on decreasing the transformation rate of polyunsaturated fatty acids to saturated fatty acids in the biohydrogenation environment. Supplements of nanoemulsified oil blends tended to be more effective than supplements of raw oils in preserving a greater proportion of polyunsaturated fatty acids in the fermentation culture. PMID- 26547648 TI - New insights into the importance of prolactin in dairy ruminants. AB - In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9 wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5 wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4 wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary infection, suggesting that PRL inhibition could be an alternative strategy for facilitating drying-off. Prolactin appears to directly affect mammary gland functions, but mammary gland responsiveness to PRL appears to be modulated by local and systemic factors. Therefore, the modulation of the number and isoforms of the PRL receptors as well as the expression of intracellular modulators of cell signaling in the mammary gland require further investigation. In conclusion, these data, combined with those from other studies, provide a good body of evidence that PRL is galactopoietic in dairy ruminants. PMID- 26547649 TI - Short communication: Regulation of hepatic gluconeogenic enzymes by dietary glycerol in transition dairy cows. AB - Nutritional status and glucose precursors are known regulators of gluconeogenic gene expression. Glycerol can replace corn in diets fed to dairy cows and use of glycerol is linked to increased rumen propionate production. The effect of dietary glycerol on the regulation of gluconeogenic enzymes is unknown. The objective of this study was to examine the effect of glycerol on expression of pyruvate carboxylase (PC), cytosolic and mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-C and PEPCK-M), and glucose-6-phosphatase. Twenty-six multiparous Holstein cows were fed either a control diet or a diet where high moisture corn was replaced by glycerol from -28 through +56 d relative to calving (DRTC). Liver tissue was collected via percutaneous liver biopsy at -28, -14, +1, +14, +28, and +56 DRTC for RNA analysis. Expression of PC mRNA increased 6-fold at +1 and 4-fold at +14 DRTC relative to precalving levels. Dietary glycerol did not alter expression of PC mRNA expression. Expression of PEPCK-C increased 2.5 fold at +14 and 3-fold at +28 DRTC compared with +1 DRTC. Overall, dietary glycerol increased PEPCK-C expression compared with that of cows fed control diets. The ratio of PC to PEPCK-C was increased 6.3-fold at +1 DRTC compared with precalving and tended to be decreased in cows fed glycerol. We detected no effect of diet or DRTC on PEPCK-M or glucose-6-phosphatase mRNA, and there were no interactions of dietary treatment and DRTC for any transcript measured. Substituting corn with glycerol increased the expression of PEPCK-C mRNA during transition to lactation and suggests that dietary energy source alters hepatic expression. The observed increase in PEPCK-C expression with glycerol feeding may indicate regulation of hepatic gene expression by changes in rumen propionate production. PMID- 26547650 TI - Monitoring individual cow udder health in automated milking systems using online somatic cell counts. AB - This study presents and validates a detection and monitoring model for mastitis based on automated frequent sampling of online cell count (OCC). Initially, data were filtered and adjusted for sensor drift and skewed distribution using ln transformation. Acceptable data were passed on to a time-series model using double exponential smoothing to estimate level and trends at cow level. The OCC levels and trends were converted to a continuous (0-1) scale, termed elevated mastitis risk (EMR), where values close to zero indicate healthy cow status and values close to 1 indicate high risk of mastitis. Finally, a feedback loop was included to dynamically request a time to next sample, based on latest EMR values or errors in the raw data stream. The estimated EMR values were used to issue 2 types of alerts, new and (on-going) intramammary infection (IMI) alerts. The new alerts were issued when the EMR values exceeded a threshold, and the IMI alerts were issued for subsequent alerts. New alerts were only issued after the EMR had been below the threshold for at least 8d. The detection model was evaluated using time-window analysis and commercial herd data (6 herds, 595,927 milkings) at different sampling intensities. Recorded treatments of mastitis were used as gold standard. Significantly higher EMR values were detected in treated than in contemporary untreated cows. The proportion of detected mastitis cases using new alerts was between 28.0 and 43.1% and highest for a fixed sampling scheme aiming at 24h between measurements. This was higher for IMI alerts, between 54.6 and 89.0%, and highest when all available measurements were used. The lowest false alert rate of 6.5 per 1,000 milkings was observed when all measurements were used. The results showed that a dynamic sampling scheme with a default value of 24h between measurements gave only a small reduction in proportion of detected mastitis treatments and remained at 88.5%. It was concluded that filtering of raw data combined with a time-series model was effective in detecting and monitoring mastitis status in dairy cows when based on IMI alerts, and by using a dynamically adjusting sampling scheme almost full performance was still obtainable. However, results were less desirable when based on new alerts most likely because of the used gold standard for mastitis, which may not necessarily reflect the onset of and IMI case in contrast to a new alert. PMID- 26547651 TI - Short communication: Changes in the composition of yak colostrum during the first week of lactation. AB - Although the great interest has been paid to colostrum utilization for calves, no systematic studies evaluating the compositional changes of yak colostrum during the first week after parturition have been reported. The aim of this study was to elucidate such postpartum nutritional changes. Colostrum samples from 12 multiparous (2-7 lactations) yaks, grazed on alpine pasture, were collected at exactly 1, 24, 48, 72, 96, 120, 144, and 168 h postpartum. Gross composition (fat, total solids, protein, and ash) were measured, as well as fat and water soluble vitamins, fatty acid and mineral composition, and IgG. The colostrum, collected 1h postpartum, had the highest concentrations of crude protein, total solids, ash, vitamin A and E, beta-carotene, and most minerals (Na, Mg, Zn, Cu, and Fe). These components decreased rapidly within 24h. Similarly, at 24h postpartum, IgG content decreased to 7.5% of the value (87.78 mg/mL) at 1h postpartum. In contrast, the concentration of vitamin C increased from 1 to 24h and then decreased consistently thereafter to the lowest value at 168 h. Phosphorus and Ca contents showed an increasing trend from 24 to 168 h after calving. Lactose content increased from 2.88% at 1h to 4.96% at 48 h postpartum and was steady to 168 h. Total n-3 fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and n-3-to-n-6 fatty acid ratio were proportionally similar as a percentage of total fatty acid methyl esters during the first 168 h of milk production. However, the proportion of total n-6 fatty acid content to total fatty acid methyl esters decreased from 3.07% at 1h to 2.60% at 24h. In summary, experimental results indicate colostrum should be provided to yak calves as soon as possible after birth to provide nutrients and enhance passive immunity. PMID- 26547652 TI - Prediction of phosphorus output in manure and milk by lactating dairy cows. AB - Mathematical models for predicting P excretions play a key role in evaluating P use efficiency and monitoring the environmental impact of dairy cows. However, the majority of extant models require feed intake as predictor variable, which is not routinely available at farm level. The objectives of the study were to (1) explore factors explaining heterogeneity in P output; (2) develop a set of empirical models for predicting P output in feces (Pf), manure (PMa), and milk (Pm, all in g/cow per day) with and without dry matter intake (DMI) using literature data; and (3) evaluate new and extant P models using an independent data set. Random effect meta-regression analyses were conducted using 190 Pf, 97 PMa, and 118 Pm or milk P concentration (PMilkC) treatment means from 38 studies. Dietary nutrient composition, milk yield and composition, and days in milk were used as potential covariates to the models with and without DMI. Dietary phosphorus intake (Pi) was the major determinant of Pf and PMa. Milk yield negatively affected Pi partitioning to Pf or PMa. In the absence of DMI, milk yield, body weight, and dietary P content became the major determinants of Pf and PMa. Milk P concentration (PMilkC) was heterogeneous across the treatment groups, with a mean of 0.92 g/kg of milk. Milk yield, days in milk, and dietary Ca-to-ash ratio were negatively correlated with PMilkC and explained 42% of the heterogeneity. The new models predicted Pf and PMa with root mean square prediction error as a percentage of observed mean (RMSPE%) of 18.3 and 19.2%, respectively, using DMI when evaluated with an independent data set. Some of the extant models also predicted Pf and PMa well (RMSPE%=19.3 to 20.0%) using DMI. The new models without DMI as a variable predicted Pf and PMa with RMSPE% of 22.3 and 19.6%, respectively, which can be used in monitoring P excretions at farm level. When evaluated with an independent data set, the new model and extant models based on milk protein content predicted PMilkC with RMSPE% of 12.7 to 19.6%. Although models using P intake information gave better predictions, P output from lactating dairy cows can also be predicted well without intake using milk yield, milk protein content, body weight, and dietary P, Ca, and total ash contents. PMID- 26547653 TI - Effect of rice bran as a replacement for oat grain in energy and nitrogen balance, methane emissions, and milk performance of Murciano-Granadina goats. AB - The objective of this experiment was to study the effects of substituting oat grain with rice bran on energy, nitrogen and carbon balance, methane emissions, and milk performance in dairy goats. Ten Murciano-Granadina dairy goats in late lactation (46.1 +/- 3.07 kg) were assigned to 2 treatments in a crossover design, where each goat received both treatments in 2 periods. One group of 5 goats was fed a mixed ration with 379 g of oat grain/kg of dry matter (O diet) and the other group of 5 goats was fed a diet that replaced oat grain with 379 g/kg dry matter of rice bran (RB diet). Diets were formulated to be isoenergetic and isoproteic, so bypass fat was added to reach the same amount of energy in both diets. The goats were allocated to individual metabolism cages. After 14 d of adaptation, feed intake, total fecal and urine outputs, and milk yield were recorded daily over a 5-d period. Then, gas exchange measurements were recorded individually by a mobile open-circuit indirect calorimetry system using a head box. Dry matter intake was different for both diets [1.83 +/- 0.11 vs. 1.61 +/- 0.08 (means +/- SD), for O and RB, respectively]. Metabolizable energy intake and heat production were not significantly different between diets, with average values of 1,254 [standard error of the mean (SEM) = 110.0] and 640 (SEM = 21.0) kJ/kg of BW(0.75), respectively. Significant differences were found in milk fat content (5.3 and 6.9%, SEM = 0.36; for O and RB, respectively) and milk fatty acids: medium-chain fatty acids (17.17 vs. 12.90 g/100g, SEM = 0.969; for O and RB, respectively) and monounsaturated fatty acids (20.63 vs. 28.29 g/100g, SEM = 1.973; for O and RB, respectively). Enteric CH4 emission was lower for the RB diet (23.2 vs. 30.1g/d, SEM = 2.14; for O and RB, respectively), probably because of the higher lipid content in RB diets than O diets (11.7 vs. 4.1%, respectively). Lactating goats utilized RB without detrimental effects on energy metabolism. Higher milk fat and lower CH4 emissions were observed with the RB diet compared with the O diet. PMID- 26547654 TI - Short communication: Forage particle size and fat intake affect rumen passage, the fatty acid profile of milk, and milk fat production in dairy cows consuming dried distillers grains with solubles. AB - Four ruminally cannulated Holstein cows averaging (+/- SD) 116 +/- 18 d in milk and 686 +/- 52 kg of body weight were used in a 4 * 4 Latin square design with a 2 * 2 factorial arrangement of treatments to test the effects of forage particle size and concentration of corn oil on milk fat depression. Cows were housed in individual stalls, milked daily at 0700 and 1800 h, and individually fed daily at 0900 h for ad libitum consumption allowing approximately 10% orts. Four 28-d periods, in which each cow was offered 1 of 4 total mixed rations, included reduced-fat dried distillers grains with solubles at 30% of dietary dry matter and differed in forage particle size by inclusion of chopped grass hay (LONGP) or grass hay pellets (SHORTP) and 0 or 2% corn oil (CO). Dietary treatments were 0% corn oil + short particle size (CO0+SHORTP), 0% corn oil + long particle size (CO0+LONGP), 2% corn oil + short particle size (CO2 + SHORTP), and 2% corn oil + long particle size (CO2 + LONGP). Dry matter intake and milk yield were not affected by treatment averaging 26.5 +/- 1.19 kg/d and 32.8 +/- 3.34 kg/d, respectively. A decrease was found in 3.5% fat-corrected milk with the inclusion of oil resulting in 34.6 and 26.6 +/- 2.6 kg/d for 0 and 2% oil diets, respectively. An oil * size interaction was found for milk fat concentration resulting in 2.27, 3.02, 3.62, and 3.62 +/- 0.23% for CO2+SHORTP, CO2 + LONGP, CO0 + SHORTP, and CO0 + LONGP, respectively. Fat yield was reduced from 1.22 to 0.81 +/- 0.09 kg/d with 2% oil diets. Cows consuming diets with long particle size spent 29 more minutes eating compared with the cows consuming short particle size (198 and 169 +/- 15 min/d). Rumination time decreased from 504 to 400 +/- 35 min/d for cows consuming short particle size compared with long particle size. Total chewing was reduced from 702 to 570 +/- 4 min/d when cows consumed short particle size. Feeding long particle size decreased rate of passage of dry matter from 3.38 to 2.89 +/- 0.42%/h; concomitantly mean retention time increased from 31.7 to 38.4 +/- 5.36 h for diets containing long particle size. The results of this experiment show that effects of oil on milk fat depression were less severe when cows consumed long particle size, suggesting that dietary manipulations that modify rumen kinetics also affect milk fat production in dairy cows consuming reduced-fat dried distillers grains with solubles supplemented with corn oil. PMID- 26547655 TI - Dairy heifers benefit from the presence of an experienced companion when learning how to graze. AB - Pasture remains important on many dairy farms, but the age of first contact with pasture varies depending on the month of birth, weaning age, and farm management. Regardless of age, naive dairy heifers must learn to graze when first introduced to pasture. This study investigated whether being grouped with experienced dairy cows would affect the development of grazing behaviors. Sixty-three Holstein heifers (mean +/- SD 14.2 +/- 1.3 mo; 546 +/- 60.7 kg) and 21 dry Holstein cows (2.6 +/- 0.8 lactations; 751 +/- 53.9 kg) were assigned into 7 groups of 12 animals (3 dry cows and 9 naive heifers), and each was divided and assigned to an experienced (3 cows and 3 heifers) and nonexperienced (6 heifers) sub-group. Sub groups were introduced to pasture in different paddocks without visual contact with any other cattle. No difference was found in the time after introduction to the paddock for heifers to first attempt to nibble grass [experienced: 0:23 (0:17 0:43) vs. nonexperienced 0:40 (0:35-0:46); median (quartile 1 - quartile 3), h:mm]. However, heifers grouped with experienced cows showed a shorter latency to begin grazing [experienced: 0:47 (0:28-00:52) vs. nonexperienced 2:13 (1:25 2:30)]. During the first hour after introduction to pasture, heifers in the experienced treatment showed fewer stomping events [experienced: 2.5 (1.25-4) vs. nonexperienced: 6.5 (4-8)] and vocalized less often [experienced: 3.5 (1.25-5.75) vs. nonexperienced: 7 (5-8.75)]. After this initial period, animals in both subgroups began to graze normally; treatments did not differ in grazing behaviors over the 3-d observation period. These results indicate that grouping heifers with pasture-experienced cows improves grazing behavior of dairy heifers in the first hours following introduction to pasture. PMID- 26547656 TI - Relationships between functional genes in Lactobacillus delbrueckii ssp. bulgaricus isolates and phenotypic characteristics associated with fermentation time and flavor production in yogurt elucidated using multilocus sequence typing. AB - Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) is well known for its worldwide application in yogurt production. Flavor production and acid producing are considered as the most important characteristics for starter culture screening. To our knowledge this is the first study applying functional gene sequence multilocus sequence typing technology to predict the fermentation and flavor-producing characteristics of yogurt-producing bacteria. In the present study, phenotypic characteristics of 35 L. bulgaricus strains were quantified during the fermentation of milk to yogurt and during its subsequent storage; these included fermentation time, acidification rate, pH, titratable acidity, and flavor characteristics (acetaldehyde concentration). Furthermore, multilocus sequence typing analysis of 7 functional genes associated with fermentation time, acid production, and flavor formation was done to elucidate the phylogeny and genetic evolution of the same L. bulgaricus isolates. The results showed that strains significantly differed in fermentation time, acidification rate, and acetaldehyde production. Combining functional gene sequence analysis with phenotypic characteristics demonstrated that groups of strains established using genotype data were consistent with groups identified based on their phenotypic traits. This study has established an efficient and rapid molecular genotyping method to identify strains with good fermentation traits; this has the potential to replace time-consuming conventional methods based on direct measurement of phenotypic traits. PMID- 26547657 TI - Effect of a phase I Coxiella burnetii inactivated vaccine on body temperature and milk yield in dairy cows. AB - Q fever is a zoonotic disease caused by Coxiella burnetii. The pathogen is prevalent in ruminants (goats, sheep, cows), which are the main sources of human infection. In the cattle industry around the world, animal (15 to 20%) and herd (38 to 72%) level prevalences of C. burnetii are high. Vaccination of ruminants against Q fever is considered important to prevent spreading of the disease and risk of infection in humans. However, published information on side effects of the Q fever vaccination under field conditions is limited for cows. The objective of this study was to investigate the effect of the phase I C. burnetii inactivated vaccine Coxevac on body temperature and milk yield in dairy cows. In 2 experiments, a total of 508 cows were randomly divided into 2 groups to determine the effect of first vaccination on body temperature and milk yield. The C. burnetii serostatus of all cows was tested before vaccination with an indirect ELISA. The first experiment took place in the teaching and research barn of the Clinic of Animal Reproduction at the Freie Universitat Berlin. Temperature was measured vaginally in 10 cows in a crossover design. The second experiment was conducted on a commercial dairy farm. Milk yield of 498 cows was measured 1 wk before and 1 wk after vaccination. In a subset of 41 cows, temperature was measured rectally. In both experiments, body temperature increased significantly after vaccination (1.0 +/- 0.9 degrees C and 0.7 +/- 0.8 degrees C). A significant difference was also found in body temperature between vaccinated and control cows. Thirty percent of the vaccinated animals in experiment 1 showed reversible swelling at the injection site as a reaction to the vaccination. The results indicate that vaccination against Q fever causes a transient increase of body temperature that peaks in the first 12 to 24h and declines after that. In experiment 2, vaccinated cows (26.8 +/- 0.39 kg/d) produced significantly less milk than did control cows (28.2 +/- 0.44 kg/d) 7d after first vaccination. The cumulative milk loss after first vaccination was influenced by an interaction between C. burnetii serostatus and average milk yield 7d before first vaccination. This was considered as part of the physiological immune response. Three out of 10 vaccinated animals in experiment 1 showed painful swelling of the skin at the injection site, which had a maximum size of 14.0 * 14.0 * 1.1cm. In conclusion, a transient increase of body temperature and a decrease in milk yield is prevalent after Coxevac vaccination. PMID- 26547658 TI - Dislodgement resistance of calcium silicate-based materials from root canals with varying thickness of dentine. AB - AIM: To evaluate the dislodgement resistance of DiaRoot BioAggregate and Biodentine from canals in roots with varying amounts of remaining dentine thickness. METHODOLOGY: A total of 90 maxillary incisor teeth with similar dimensions were used. The teeth were extracted for periodontal reasons from adult subjects aged between 52 and 61 years. They were decoronated at the cemento enamel junction. Simulated internal cavities with a depth of 3 mm were performed by widening the canals on the coronal thirds of the roots, leaving varying amounts of remaining dentine thickness. The canals were enlarged progressively using round diamond burs until the desired dentine wall thickness was obtained. The samples were divided into three main groups (n = 30 each) according to the dentine thickness as follows: group 1: dentine thickness of 0.75 mm, group 2: dentine thickness of 1.50 mm and group 3: dentine thickness of 2.25 mm. Then, these main groups were further divided into two subgroups (n = 15 each) according to the filling material (DiaRoot BioAggregate or Biodentine). Horizontal root slices of 1 mm were obtained from each specimen. Vertical loading was applied to the filling materials at a cross-head speed of 1 mm min-1 using a universal testing machine. The force that led to dislodgement of the filling was recorded in Newtons. The resistance to dislodgement was calculated in megapascals (MPa) by dividing the load in Newtons by the area of the bonded interface. The data were statistically analysed with two-way anova with Tukey's honestly significant difference (HSD) test. RESULTS: Biodentine had significantly higher resistance to dislodgement than DiaRoot BioAggregate (P < 0.001). The specimens with thinner remaining dentine had lower dislodgement resistance compared to those with dentine thicknesses of 1.50 and 2.25 mm (P < 0.001). The lowest mean value for dislodgement resistance was obtained from the DiaRoot BioAggregate group with 0.75 mm dentine thickness (2.72 +/- 0.90 MPa). CONCLUSION: The dislodgement resistance of Biodentine and DiaRoot BioAggregate from root dentine was influenced by remaining dentine thickness, which determines dentinal tubular density. PMID- 26547659 TI - Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects. AB - We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony defect, and its efficacy was superior in rhFGF-2 compared to EMD treatments. PMID- 26547660 TI - Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A. AB - BACKGROUND AND OBJECTIVE: The use of cyclosporine A induces fibrous enlargement of the gingival connective tissue. Existing treatment modalities, although effective, do not necessarily prevent the recurrence of the lesion. Emerging evidence indicates that tanshinone IIA (Tan IIA) could effectively attenuate a variety of fibrotic diseases. The present research aims to assess whether Tan IIA can effectively alleviate the gingival fibrous overgrowth induced by cyclosporine A. MATERIAL AND METHODS: Forty-five Wistar rats were divided into the no treatment control group, cyclosporine A-treated group and the group treated with a combination of cyclosporine A and Tan IIA. Paraffin-embedded sections of mandibular first molar regions were selected for hematoxylin and eosin staining, Masson's trichrome staining, picro-sirius red staining and immunohistochemistry analyses of transforming growth factor-beta1 (TGF-beta1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-1 (MMP-1). The gingival connective tissue area was measured and numbers of the TGF-beta1-, TIMP-1- and MMP-1-positive cells were counted. The analysis of variance for factorial designs for testing the overall differences and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. RESULTS: Cyclosporine A treatment led to overgrowth of gingival connective tissue in rats. In the cyclosporine A-treated rats, the expression of TGF-beta1 and TIMP-1 was significantly upregulated, whereas expression of the MMP-1 was downregulated, along with thicker and denser collagen fibers. In rats treated with a combination of cyclosporine A and Tan IIA, the cyclosporine A-induced changes were alleviated. CONCLUSIONS: Cyclosporine A enhanced gingival fibrous overgrowth via upregulation of the TGF-beta1 and TIMP-1 expression, and downregulation of MMP-1 expression. Tan IIA can effectively prevent cyclosporine A-induced gingival fibrous overgrowth in rats by downregulating TGF-beta1 and TIMP-1 expression, and upregulating MMP-1 expression. PMID- 26547661 TI - Evolutionary and demographic history of the Californian scrub white oak species complex: an integrative approach. AB - Understanding the factors promoting species formation is a major task in evolutionary research. Here, we employ an integrative approach to study the evolutionary history of the Californian scrub white oak species complex (genus Quercus). To infer the relative importance of geographical isolation and ecological divergence in driving the speciation process, we (i) analysed inter- and intraspecific patterns of genetic differentiation and employed an approximate Bayesian computation (ABC) framework to evaluate different plausible scenarios of species divergence. In a second step, we (ii) linked the inferred divergence pathways with current and past species distribution models (SDMs) and (iii) tested for niche differentiation and phylogenetic niche conservatism across taxa. ABC analyses showed that the most plausible scenario is the one considering the divergence of two main lineages followed by a more recent pulse of speciation. Genotypic data in conjunction with SDMs and niche differentiation analyses support that different factors (geography vs. environment) and modes of speciation (parapatry, allopatry and maybe sympatry) have played a role in the divergence process within this complex. We found no significant relationship between genetic differentiation and niche overlap, which probably reflects niche lability and/or that multiple factors, have contributed to speciation. Our study shows that different mechanisms can drive divergence even among closely related taxa representing early stages of species formation and exemplifies the importance of adopting integrative approaches to get a better understanding of the speciation process. PMID- 26547663 TI - IL-17: A promising therapeutic target for atherosclerosis. PMID- 26547662 TI - Case-control study of oral glucose-lowering drugs in combination with long-acting insulin and the risks of incident myocardial infarction and incident stroke. AB - BACKGROUND: The use of oral glucose-lowering therapies with insulin is common, but the cardiovascular effects are largely unknown. Among users of long-acting insulin, we conducted a population-based case-control study to evaluate the incident myocardial infarction (MI) and incident stroke risks associated with the use of sulfonylureas and the use of metformin. METHODS: Cases were Group Health Cooperative enrollees with type 2 diabetes who used long-acting insulin at the time of diagnosis with a first MI (n = 413) or first stroke (n = 247) from 1995 to 2010. Controls (n = 443) with type 2 diabetes who used long-acting insulin were matched to cases on age, sex, and calendar year. Sulfonylurea and metformin use was classified as current, past, or never using electronic pharmacy records. MI and stroke diagnoses were validated by medical record review. Analyses were adjusted for potential confounders. RESULTS: Current use of sulfonylureas compared with never use was associated with a higher risk of MI (odds ratio [OR] 1.67; 95% confidence interval [CI], 1.10-2.55) but not stroke (OR 1.22; 95%CI, 0.74-2.00). Current use of metformin compared with never use was associated with a lower risk of stroke (OR 0.54; 95%CI, 0.31-0.95) but not MI (OR 0.77; 95%CI, 0.44-1.33). Past use of sulfonylureas and past use of metformin were not associated with either outcome. CONCLUSIONS: Sulfonylureas in combination with long-acting insulin may increase the risk of MI compared with the use of insulin alone. Metformin may be an important cardiovascular disease prevention therapy for patients on insulin therapy. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26547664 TI - Transradial intervention versus transfemoral intervention accompanied with vascular closure device in acute myocardial infarction. PMID- 26547665 TI - Everolimus-eluting stent versus Sirolimus-eluting stent for prognostic significance. PMID- 26547666 TI - The spontaneous coronary artery dissection may need intervention in the proximal segment of the arteries. PMID- 26547667 TI - Sex-related differences in lung inflammation after brain death. AB - BACKGROUND: Donor sex has been suggested to be a factor influencing organ transplantation outcome. Sex hormones possess inflammatory and immune-mediating properties; therefore, immune responses may differ between males and females. Brain death (BD) affects organ function by numerous mechanisms including alterations in hemodynamics, hormonal changes, and increased systemic inflammation. In this study, we investigated sex-dependent differences in the evolution of lung inflammation in a rat model of BD. MATERIALS AND METHODS: BD was induced by a sudden increase in intracranial pressure by rapidly inflating a balloon catheter inserted into the intracranial space. Groups of male, female, and ovariectomized (OVx) female rats were used. Lung vascular permeability, inducible nitric oxide synthase, and intercellular adhesion molecule 1 expression were analyzed 6 h after BD. Serum female sex hormones, vascular endothelial growth factor, and cytokine-induced neutrophil chemoattractant 1 levels were also quantified. Lung sections were analyzed by histology. RESULTS: After 6 h of BD, serum estradiol and progesterone concentrations in female rats were significantly reduced. Lung microvascular permeability was increased in females compared to males. Cytokine-induced neutrophil chemoattractant 1 and vascular endothelial growth factor concentrations were increased in female rats compared to males. Furthermore, female rats showed higher levels of leukocyte infiltration and inducible nitric oxide synthase expression in the lung parenchyma. CONCLUSIONS: Our results indicate that the more severe lung inflammation in female animals after BD might be related to acute estradiol reduction. Based on our findings, we believe that, in a future study, a group of female treated with estradiol after BD could indicate a possible therapy for the control of lung inflammation in the female donor. PMID- 26547668 TI - Trajectories of smoking behavior as a function of mood and satisfaction with life: What matters most? AB - BACKGROUND: Worldwide, tobacco use causes more than 5 million deaths per year. The present study investigated possible preventative factors of nicotine dependence, such as mood and Satisfaction With Life (SWL). METHODS: Longitudinal Internet survey of 1957 individuals assessed three times at a two week interval (2007-2010). OUTCOME MEASURES: Cigarette Dependence Scale (CDS), feeling prisoner to cigarettes, smoking cessation, reduction, and relapse. PREDICTORS: Time (i.e. trajectory of dependence over time), smoking status (daily, occasional or ex smoker), mood, and SWL. All measures were assessed at each time point. RESULTS: Both SWL, and mood, respectively were significantly associated with dependence (slopeSWL=-0.03, slopeSWL=-0.11, ps<0.001). With respect to feeling prisoner to cigarettes, mood but not SWL showed a significant association (slopeSWL=-0.14, p<0.001). Occasional, and ex-smokers showed significantly greater decrease in psychological dependence, as mood increased, than daily smokers (slopeoccasional= 0.28, poccasional=0.011; slopeex=-0.27, pex<0.001). Smoking cessation decreased over time, and both mood, as well as SWL had a significant impact on cessation (ORmood=1.43, pmood<0.01, ORSWL=1.15, pSWL=0.042). Reduction in smoking was predicted by SWL only (ORSWL=1.21, p=0.043), whereas relapse was predicted by mood only (ORmood=0.55, p<0.01). LIMITATIONS: The participants were self selected. Possible confounding relationships (e.g., medication) have to be further assessed. CONCLUSIONS: Cigarette dependence, feeling prisoner to cigarettes, cessation, and reduction are significantly influenced by both mood and SWL. Treatments may thus tackle mood regulation, SWL, and nicotine dependence in tandem. PMID- 26547669 TI - [Therapeutic outcomes of anti-tuberculosis treatment in the context of HIV tuberculosis co-infection: Cohort of Kabinda Center in Kinshasa, Democratic Republic of Congo]. AB - BACKGROUND: The study aimed to determine the clinical forms of tuberculosis and therapeutic outcome of anti-tuberculosis treatment in the context of HIV tuberculosis co-infection. METHODS: A retrospective cohort of 120 HIV-positive patients with tuberculosis and 297 HIV-negative patients with tuberculosis attending the Kabinda Center was followed from 2010 to June, 30th 2013. The logistic regression model identified the determinants of a defavorable outcome after initiation of tuberculostatics. RESULTS: The proportion of female patients was higher in the co-infected group compared with the non-co-infected group (60.8% versus 42.7%, P<0.001). HIV-seropositive patients had more forms of pulmonary smear-negative (39.2% versus 25.3%, P<0.002) and extra-pulmonary (38% versus 35%, P<0.002) tuberculosis than HIV-negative patients. HIV-positive serology (OR: 3.13, 95%CI: 1.72-5.69) and age of patients more than 41 years (OR: 3.15, 95%CI: 1.36-7.29) were associated with an unfavorable outcome. CONCLUSION: This study highlights the usefulness of a systematically determining immunological status in co-infected patients and a timely and systematic ARV treatment, together with early diagnosis of tuberculosis. It also emphasizes the importance of adherence to support measures in order to improve tuberculosis treatment outcomes in co-infected patients. PMID- 26547670 TI - [Study of the immunization coverage determinants of vaccination campaign against meningococcal A meningitis in Burkina Faso]. AB - BACKGROUND: Sub-Saharan Africa countries suffer from repeated and explosive epidemics of meningitis mainly due to Neisseria meningitidis A. In December 2010, Burkina Faso organized a vaccination campaign with MenAfriVac(r) for people aged 1-29 years old. The objective of this study was to analyze the determinants of immunization coverage. METHODS: We used a cross-sectional survey by cluster sampling in two stages, descriptive and analytical, conducted in the region of "Boucle du Mouhoun". Data were collected during a home interview. The dependent variable was vaccination status and the independent variables included individual and household characteristics but also the means of communication used during the campaign. A logistic regression model was used to estimate the risk of being vaccinated using the 'Survey' Package (SVYGLM) of R. RESULTS: Two thousand and twenty-five people were included with a 93.5 % estimated coverage. Factors associated with high vaccination coverage are rural areas (ORa=2.53 [1.53-4.17]) and smaller households (ORa=3.06 [1.36-6.91]). The risk of being vaccinated was lower for persons from salaried heads of household (ORa=0.14 [0.02-0.87]) versus farmers, persons informed by religious and traditional leaders (ORa=0.25 [0.11 0.57]) or family and friends (ORa=0.51 [0.29-0.9]) versus community mobilizers. CONCLUSION: The coverage recorded is sufficient to provide community immunity. However, a part of the target population could not benefit from vaccination due to lack of information. Particular emphasis should be placed on large urban families using community mobilizers. PMID- 26547671 TI - High serum iron level is associated with an increased risk of hypertensive disorders during pregnancy: a meta-analysis of observational studies. AB - The exact cause of hypertensive disorders in pregnancy (HDP) has not been clearly elucidated. Some researchers have recently investigated the relationship between the serum iron level and the incidence of HDP. However, the results are inconsistent, and these data have not been systematically evaluated. Therefore, we conducted a meta-analysis to evaluate the real association between the serum iron level and the incidence of HDP. We searched for published and ongoing trials in PubMed, EMBASE, Scopus, Web of Science, the Chinese Biomedical Database, CNKI, and the WANFANG database from January 1990 to May 2015 to identify studies that met our predefined criteria. Finally, 26 studies, including 1 cross-sectional study, 23 case-control studies, and 2 prospective nested case-control studies, including 1349 patients and 1119 control participants, were selected for this meta-analysis. The pooled results show that a high serum iron level increased the incidence of HDP (standard mean deviation [SMD], 1.50; 95% confidence interval [CI], 0.94-2.06; P < .0001), especially gestational hypertension (SMD, 3.65; 95% CI, 1.50-5.81; P = .0009) and preeclampsia (SMD, 1.27; 95% CI, 0.76-1.78; P < .0001). No significant difference was seen between the eclampsia groups and the control participants (SMD, 3.34; 95% CI, -0.02 to 6.69; P = .05). The results of this meta-analysis indicate that a high serum iron level is associated with an increased risk of HDP, especially gestational hypertension and preeclampsia. PMID- 26547672 TI - Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. AB - Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 MUg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus. PMID- 26547673 TI - [Tunnelled central venous line-associated infections in patients with pulmonary arterial hypertension treated with intravenous prostacyclin]. AB - Intravenous prostacyclins are a valuable treatment for patients with severe pulmonary arterial hypertension, leading to improved exercise capacity, haemodynamics, quality of life and survival. Unfortunately, due to the short half life of these drugs, they need to be administered continuously through central venous catheters. Despite aseptic technique, regular dressing changes, tunneled central venous catheters and patient education, patients are exposed to central venous catheter associated infections. These infections cause significant morbidity and mortality. The clinical presentation, microbiology, consequences and management of these central venous catheter associated infections in pulmonary arterial hypertension patients treated with intravenous prostacyclins are discussed. PMID- 26547674 TI - [Air pollution]. AB - Short-term exposure to particulate matter (PM) air pollution is associated with an increased cardiovascular mortality. Chronic exposure to PM is also associated with cardiovascular risk. Myocardial infarction and heart failure are the most common cardiovascular events associated with PM pollution. The pathophysiological mechanisms related to PM pollution are inflammation, thrombosis, vasomotion abnormalities, progression of atherosclerosis, increased blood pressure, and cardiac remodeling. A decrease in PM exposure may be particularly beneficial in subjects with a high cardiovascular risk. PMID- 26547675 TI - Pulmonary embolism: Epidemiology and registries. AB - Real-life data is important in understanding the needs of patients in routine clinical practice, particularly owing to the fact that almost a quarter of patients with venous thromoboembolism (VTE) have at least one exclusion criterion preventing their recruitment into randomized clinical trials. The Registro Informatizado de Enfermedad Trombo Embolica (RIETE) registry is an ongoing, international, multicentre, prospective registry of consecutive patients presenting with acute VTE. In this chapter, we summarized some of the most relevant data concerning the epidemiology of VTE in the RIETE registry. PMID- 26547676 TI - [Cluster headache treatment]. AB - Acute treatment: sumatriptan, oxygen inhalation. Prophylactic treatment: verapamil, lithium carbonate. Transitional treatment. SURGICAL TREATMENT: deep brain stimulation, occipital nerve stimulation, stimulation of the sphenopalatin ganglion. PMID- 26547677 TI - Pulmonary embolism: An update. PMID- 26547678 TI - Treatment of pulmonary embolism. AB - The treatment of pulmonary embolism is going to be deeply modified by the development of Direct Oral Anticoagulants (DOACs). There are currently three anti Xa factors (rivaroxaban, apixaban, edoxaban) and one anti-IIa factor (dabigatran) labeled by the FDA and the EMA. All these drugs are direct anticoagulant, orally effective, without the need for adaptation to hemostasis test. As kidney excretion is involved for all of them, they are contra-indicated in patients with severe renal failure (creatinine clearance < 30 mL/min according to Cockcroft & Gault formula). All the anti-Xa factor drugs are metabolized by liver cytochromes and then contra-indicated in case of liver insufficiency. Of note, the four DOACS have been evaluated in non-inferiority trials, including one open-label trial (the EINSTEIN program with the rivaroxaban). Moreover, two of them (rivaroxaban and apixaban) were evaluated in a single drug approach (provided initial increased doses: 15 mg bid during 21 days for rivaroxaban and 10 mg bid during 7 days for apixaban) whereas the two others (edoxaban and dabigatran) were evaluated after at least 5 days of parenteral heparin. They were found to be non inferior to the conventional treatment, but also seem to be associated with a decreased risk of major bleeding, in a quite young and without significant comorbidities population. The risk/benefit ratio of DOACs in specific subgroups deserves prospective validations. PMID- 26547679 TI - Nurse migration--from the outside in. PMID- 26547680 TI - Changes in dimensions of total knee arthroplasty anterior knee dressings during flexion: Preliminary findings. AB - INTRODUCTION: Wound care is critical to the management of patients post total knee arthroplasty, requiring prudent selection of dressings that can accommodate changes in wound length during knee flexion. This study aims to quantify differences in dressing dimensions based on the position of the knee during the application of the dressing and subsequent flexion. METHODS: Our study involved 40 knees divided into 2 groups, an extension group and a flexion group, each consisting of 20 knees. These groups had dressings applied to the knee in full extension and in 90 degrees of flexion respectively. Measurements of the dressings were taken for the extension group with the knee in extension and for both groups at 90 degrees of flexion. RESULTS: For the extension group, the changes in length and breadth of the dressings when measured in 90 degrees of flexion were 3.42 +/- 0.15 cm, p < 0.001 and -0.43 +/- 0.10 cm, p < 0.001 respectively. Compared to the flexion group, the differences in length and breadth between the dressings when measured in 90 degrees of flexion were 3.48 +/- 0.15 cm, p < 0.001 and -0.14 +/- 0.12 cm, p < 0.001 respectively. CONCLUSION: There are significant differences and changes in the dimensions of knee dressings depending on the position of the knee during the application of dressing and subsequent flexion. PMID- 26547681 TI - Evaluating the orthogeriatric model of care at an Australian tertiary hospital. AB - INTRODUCTION: The management of fragility hip fractures requires a collaborative multi-disciplinary approach to care to ensure optimal patient outcomes. It is important to rigorously evaluate the model of care and enable the delivery of evidence based optimal patient care. AIM OF THE STUDY: The aim of this study was to document an orthogeriatric model of care (OGMOC) at a major tertiary hospital: assessing how particular indicators within the patient's admission were influenced by the OGMOC. METHODS: A retrospective case analysis of all patients with fragility hip fracture from two pre-intervention groups and three post intervention groups was undertaken. Data from (i) length of stay in the emergency department (ii) length of stay in the orthopaedic unit (iii) time from admission to surgery and (iv) time from surgery to admission to rehabilitation were used. RESULTS: Implementation of the OGMOC resulted in: reduced time in the emergency department, quicker access to surgery, reduced length of acute hospital stay and an increase in the number of patients accessing the rehabilitation unit. CONCLUSION: This study contributes to the increasing body of evidence for best practice in the management of fragility hip fracture within an OGMOC. PMID- 26547683 TI - Commissioning, implementation and delivery of an interface secondary fracture prevention service within the NHS: Lessons learnt from the Oxfordshire Fracture Prevention Service. AB - AIMS: To provide a case history of the service model, commissioning, implementation and delivery of an interface secondary fracture prevention service. BACKGROUND: Fracture Prevention has been identified as key to reducing the burden on the NHS from an ageing population. The need to have a systematic process for identifying, assessing and ensuring treatment adherence is vital. RATIONALE: Delivering the service to identify patients at risk and initiate treatment is important as is the use of a database for patient tracking and the need to ensure that patients remain on treatment to ensure maximum fracture prevention benefit, and cost savings are seen. The process for implementing a Fracture Prevention service can be challenging but identifying the components and working closely with local commissioners can provide the evidence and release the resource required. SUMMARY: The key components of a Fracture Prevention Service should include robust case-finding, assessment, treatment initiation, patient education and monitoring. PMID- 26547682 TI - Optimizing physical activity among older adults post trauma: Overcoming system and patient challenges. AB - BACKGROUND: By 2050 it is anticipated that close to half (40%) of all trauma patients will be over the age of 65. Recovery for these individuals is more complicated than among younger individuals. Early mobilization has been shown to improve outcomes. Unfortunately, there are many challenges to early mobilization. The Function Focused Care Intervention was developed to overcome these challenges. PURPOSE: The purpose of this paper was to describe the initial recruitment of the first 25 participants and delineate the challenges and successes associated with implementation of this intervention. RESULTS: Overall recruitment rates were consistent with other studies and the intervention was implemented as intended. Most patients were female, white and on average 79 years of age. Optimizing physical activity of patients was a low priority for the nurses with patient safety taking precedence. Patients spent most of the time in bed. Age, depression and tethering were the only factors that were associated with physical activity and functional outcomes of patients. CONCLUSION: Ongoing work is needed to keep patients physically active in the immediate post trauma recovery period. PMID- 26547684 TI - Delirium detection and improved delirium management in older patients hospitalized for hip fracture. AB - Delirium is a common and potentially devastating problem for older patients following hip fracture. Although early detection is recommended, description and evaluation of standardized approaches are scarce. The aims of this quality improvement project were to: (1) implement a clinical algorithm for improving delirium detection and management and (2) assess the impact of the clinical algorithm on length of stay, discharge disposition and patient satisfaction. The pilot study was implemented on an orthopedic unit to evaluate the effectiveness of a clinical protocol for delirium detection and management to improve outcomes. Outcomes of 33 elderly post-operative hip fracture patients were compared to historical controls from the same unit. Delirium was detected in 18% of patients. Length of stay was reduced by 22% (P < .001), discharge disposition showed a 13% improvement (P = .17) and patient satisfaction scores showed a 15% (P = .15) improvement post-intervention. Implementation of a clinical algorithm to promote early detection and treatment of delirium in post-operative hip fracture patients is feasible and associated with improved outcomes. PMID- 26547685 TI - A day in the life of orthopaedic and trauma practitioners: Advanced Nurse Practitioner Sarcoma. PMID- 26547688 TI - Being lonely or using substances with friends? A cross-sectional study of Hungarian adolescents' health risk behaviours. AB - BACKGROUND: Studying adolescents' health risk behaviours is oddly significant in Central and Eastern European countries, where the prevalence of smoking and drinking among 14-18 year old students is significantly high. The goal of our study is to examine the role of social psychological and social behavioural variables in health risk behaviours among Hungarian adolescents. METHODS: Our sample was comprised of three high schools of Debrecen (the second largest city of Hungary). In all, 501 students filled in the questionnaire from 22 classes (14 22 years old). Students aged above 18 years were excluded for the purpose of the study, giving a total sample size of 471 high school students. Descriptive statistics and binary logistic regression analyses were conducted. RESULTS: According to our results (1) social behavioural factors (namely, smoking and alcohol use of the best friend and peer group) proved to be better predictors of adolescents' health risk behaviours as compared to the included social psychological attributes (2); among the latter ones, loneliness and shyness were negatively related with both smoking and drinking, while competitiveness was a predictor of drinking prevalence among boys. CONCLUSIONS: The findings suggest that social behavioural factors, including smoking and drinking of friends, are oddly important predictors of Hungarian adolescents' health risk behaviours. According to our results, health policy should pay more attention to peer norms related to smoking and drinking during school health promotion. Developing health protective social norms may be an indispensable component of effective health promotion in high schools. PMID- 26547687 TI - Fidelity to and comparative results across behavioral interventions evaluated through the RE-AIM framework: a systematic review. AB - BACKGROUND: The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework was developed to determine potential public health impact of interventions (i.e., programs, policy, and practice). The purpose of this systematic review was to determine (1) comparative results across accurately reported RE-AIM indicators, (2) relevant information when there remains under reporting or misclassification of data across each dimension, (3) the degree to which authors intervened to improve outcomes related to each dimension, and (4) the number of articles reporting RE-AIM dimensions for a given study. METHODS: In April 2013, a systematic search of the RE-AIM framework was completed in PubMed, PSYCHInfo, EbscoHost, Web of Science, and Scopus. Evidence was analyzed until January 2015. RESULTS: Eighty-two interventions that included empirical data related to at least one of the RE-AIM dimensions were included in the review. Across these interventions, they reached a median sample size of 320 participants (M = 4894 +/- 28,256). Summarizing the effectiveness indicators, we found that: the average participation rate was 45 % (+/-28 %), 89 % of the interventions reported positive changes in the primary outcome and 11 interventions reported broader outcomes (e.g., quality of life). As for individual-level maintenance, 11 % of studies showed effects >=6 months post-program. Average setting and staff adoption rates were 75 % (+/-32 %) and 79 % (+/-28 %), respectively. Interventions reported being delivered as intended (82 % (+/-16 %)) and 22 % intervention reported adaptations to delivery. There were insufficient data to determine average maintenance at the organizational level. Data on costs associated with each dimension were infrequent and disparate: four studies reported costs of recruitment, two reported intervention costs per participant, and two reported adoption costs. CONCLUSIONS: The RE-AIM framework has been employed in a variety of populations and settings for the planning, delivery, and evaluation of behavioral interventions. This review highlights inconsistencies in the degree to which authors reported each dimension in its entirety as well as inaccuracies in reporting indicators within each dimension. Further, there are few interventions that aim to improve outcomes related to reach, adoption, implementation, and maintenance. PMID- 26547689 TI - Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia. AB - BACKGROUND: Tumor-suppressor genes are inactivated by methylation in several cancers including acute myeloid leukemia (AML). Src homology-2 (SH2)-containing protein-tyrosine phosphatase 1 (SHP-1) is a negative regulator of the JAK/STAT pathway. Transcriptional silencing of SHP-1 plays a critical role in the development and progression of cancers through STAT3 activation. 5-Azacytidine (5 Aza) is a DNA methyltransferase inhibitor that causes DNA demethylation resulting in re-expression of silenced SHP-1. Lestaurtinib (CEP-701) is a multi-targeted tyrosine kinase inhibitor that potently inhibits FLT3 tyrosine kinase and induces hematological remission in AML patients harboring the internal tandem duplication of the FLT3 gene (FLT3-ITD). However, the majority of patients in clinical trials developed resistance to CEP-701. Therefore, the aim of this study, was to assess the effect of re-expression of SHP-1 on sensitivity to CEP-701 in resistant AML cells. METHODS: Resistant cells harboring the FLT3-ITD were developed by overexposure of MV4-11 to CEP-701, and the effects of 5-Aza treatment were investigated. Apoptosis and cytotoxicity of CEP-701 were determined using Annexin V and MTS assays, respectively. Gene expression was performed by quantitative real-time PCR. STATs activity was examined by western blotting and the methylation profile of SHP-1 was studied using MS-PCR and pyrosequencing analysis. Repeated-measures ANOVA and Kruskal-Wallis tests were used for statistical analysis. RESULTS: The cytotoxic dose of CEP-701 on resistant cells was significantly higher in comparison with parental and MV4-11R-cep + 5-Aza cells (p = 0.004). The resistant cells showed a significant higher viability and lower apoptosis compared with other cells (p < 0.001). Expression of SHP-1 was 7 fold higher in MV4-11R-cep + 5-Aza cells compared to parental and resistant cells (p = 0.011). STAT3 was activated in resistant cells. Methylation of SHP-1 was significantly decreased in MV4-11R-cep + 5-Aza cells (p = 0.002). CONCLUSIONS: The restoration of SHP-1 expression induces sensitivity towards CEP-701 and could serve as a target in the treatment of AML. Our findings support the hypothesis that, the tumor-suppressor effect of SHP-1 is lost due to epigenetic silencing and its re-expression might play an important role in re-inducing sensitivity to TKIs. Thus, SHP-1 is a plausible candidate for a role in the development of CEP 701 resistance in FLT3-ITD+ AML patients. PMID- 26547690 TI - Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent. AB - Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 kinase activity, as well as growth of several pancreatic cancer cell lines. In a mouse xenograft model, 11 inhibited growth of human pancreatic cancer cell line PCI66 with negligible body weight loss. Thus, 11 appears to be a promising lead compound for further optimization to develop new anti-pancreatic cancer agents. PMID- 26547691 TI - 2-(Nitroaryl)benzothiazole and benzoxazole derivatives as fluorogenic substrates for the detection of nitroreductase activity in clinically important microorganisms. AB - A series of carboxy-substituted 2-(nitroaryl)benzothiazole derivatives and carboxy-substituted 2-(nitroaryl)benzoxazole derivatives were prepared and evaluated as potential nitroreductase substrates for the purpose of detecting clinically important microorganisms. Several of the substrates produced highly fluorescent colonies with the majority of a panel of 10 Gram-negative bacteria and also with two of a panel of 8 Gram-positive bacteria. PMID- 26547692 TI - Protective effects of 5,7,4'-trihydroxy-6,3'dimethoxy-flavone 5-O-alpha-l rhamnopyranoside, isolated from Annona squamosa leaves in thyrotoxicosis and in hepatic lipid peroxidation in rats. AB - Hitherto unknown protective effects of 5,7,4'-trihydroxy-6,3'dimethoxy-flavone 5 O-alpha-l-rhamnopyranoside (THDMF-Rha); isolated from Annona squamosa leaves were evaluated in l-thyroxine (l-T4)-induced thyrotoxicosis in rats. Administration of l-T4 at 500MUg/kg body weight for 12days increased the levels of serum thyroid hormones, the activity of 5'-monodeiodinase-I (5'DI) and hepatic glucose-6 phosphatase (G-6Pase) as well as lipid peroxidation (LPO); with a parallel decrease in the levels of cellular antioxidants and serum lipids. However, administration of the isolated THDMF-Rha at a pre-standardized dose for 15days ameliorated the l-T4-induced alterations in the levels of thyroid hormones, hepatic LPO, G-6-Pase, 5'DI activity, and cellular levels of antioxidants and improved the status of different serum lipids, suggesting its antithyroidal and antioxidative potential. As compared to standard antithyroid drug, propylthiouracil, THDMF-Rha appeared to be more promising. PMID- 26547693 TI - A new cerebroside from the fruiting bodies of Hericium erinaceus and its applicability to cancer treatment. AB - A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment. PMID- 26547694 TI - 45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims? AB - AIMS: In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. MATERIALS AND METHODS: The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. RESULTS: A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 +/- 8.0 versus 82.4 +/- 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. CONCLUSION: The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions. PMID- 26547695 TI - Type 2 Diabetes Self-management Among Spanish-Speaking Hispanic Immigrants. AB - This article describes the quantitative findings of a mixed-methods study that examined the relationship among knowledge, self-efficacy, health promoting behaviors, and type 2 diabetes self-management among recent Spanish-speaking, limited English proficient immigrants to the US. This population is at risk for both a higher incidence of disease and increased barriers to successful disease management compared to the general US population. Distinguishing aspects of this study compared to the available literature are the comprehensive nature of the data collected, the theoretical component, and the analysis and modeling approach. Social cognitive theory provides the framework for the study design and analysis. An innovative community-based recruiting strategy was used, a broad range of physiological measures related to health were observed, and instruments related to knowledge, self-efficacy, and healthy lifestyle behaviors were administered orally in Spanish to 30 participants. A broad range of statistical analysis methods was applied to the data, including a set of three structural equation models. The study results are consistent with the importance of education, health knowledge, and healthy lifestyle practices for type 2 diabetes self-management. With the usual cautions associated with applying structural equation modeling to modest sample sizes, multiple elements of the posited theoretical model were consistent with the data collected. The results of the investigation of this under-studied population indicate that, on average, participants were not effectively managing their disease. The results suggest that clinical interventions focused on improving knowledge, nutrition, and physical activity, reducing stress, and leveraging the importance of interpersonal relations could be effective intervention strategies to improve self-management among this population. PMID- 26547697 TI - Breaking a Tradition; the 2016 Honoree. PMID- 26547696 TI - A Matter of Taste? Quality of Life in Day-to-Day Living with ALS and a Feeding Tube. AB - Although people often refer to quality of life and there is a respectable research tradition to establish it, the meaning of the term is unclear. In this article we qualitatively study an intervention of which the quantitative effects are documented as indecisive. We do this in order to learn more about what the meaning of the term quality of life means when it is studied in daily life. With the help of these findings we reflect on the intricacies of objectifying and measuring quality of life using quantitative research designs. Our case is the feeding tube for patients suffering from ALS, a severe motor neuron disease that rapidly and progressively incapacitates patients. We studied how these patients, who lived in the Netherlands, anticipated and lived with a feeding tube in the course of their physical deterioration. Our analysis shows that the quality of life related to the feeding tube has to be understood as a process rather than as an outcome. The feeding tube becomes a different thing as patients move through the various phases of their illness, due to changes in their condition, living circumstances, and concerns and values. There are very different appreciations of the way the feeding tube changes the body's appearance and feel. Some patients refuse it because they feel it disfigures their body, whereas others are indifferent to its appearance. Our conclusion is that these differences are difficult to grasp with a quantitative study designs because 'matters of taste' and values are not distributed in a population in the same ways as physiological responses to medication. Effect studies assume physiological responses to be more or less the same for everyone, with only gradual differences. Our analysis of quality in daily life, however, shows that what a treatment comes to be and how it is valued shows shows generalities for subgroups rather than populations. PMID- 26547698 TI - Does smoking affect gingival crevicular fluid LL-37 levels following non-surgical periodontal treatment in chronic periodontitis? AB - OBJECTIVE: LL-37 contributes to maintaining the balance between health and disease. Smoking is a risk factor for periodontitis that impairs neutrophil functions. The aim of the present study was to comparatively evaluate gingival crevicular fluid (GCF) LL-37 levels in smoker and non-smoker chronic periodontitis (CP) patients and controls, as well as the effect of non-surgical periodontal treatment on GCF LL-37 levels. DESIGN: Thirty-one CP patients (16 smokers, 15 non-smokers) and thirty-one controls (16 smokers, 15 non-smokers) were included in the study. CP patients received non-surgical treatment. GCF LL 37 levels and periodontal parameters were assessed at baseline, 1 and 3 months after completion of non-surgical periodontal treatment. GCF LL-37 levels were analyzed by ELISA. RESULTS: No significant difference was observed in GCF LL-37 levels between smoker and non-smoker controls (p>0.05). Smoker CP group had significantly lower GCF LL-37 level than non-smoker CP group at baseline (p<0.05). GCF LL-37 levels significantly decreased in non-smoker CP group at first week, 1 and 3 months after completion of non-surgical periodontal treatment (p<0.05) although no significant decrease in GCF LL-37 levels was observed in smoker CP group (p>0.05). Periodontal parameters were correlated with GCF LL-37 levels in non-smoker CP group (p<0.05), but not in smoker CP group (p>0.05). CONCLUSIONS: GCF LL-37 levels do not seem to be affected from smoking in periodontal health. However, smoking might have a suppressive effect on GCF LL-37 levels in CP. Non-surgical treatment is effective in decreasing GCF LL-37 levels in non-smoker CP patients but not in smokers with CP. PMID- 26547699 TI - Complex cellular responses to tooth wear in rodent molar. AB - The arrangement and roles of the odontoblast and its process in sensing and responding to injuries such as tooth wear are incompletely understood. Evidence is presented that dentine exposure by tooth wear triggers structural and functional changes that aim to maintain tooth integrity. Mandibular first molars from freshly culled 8 week Wistar rats were prepared for light microscopy ground sections (n=6), or fixed in 4% paraformaldehyde, decalcified in 17% EDTA, sectioned and stained with antibodies to cyto-skeletal proteins (vimentin (vim), alpha-tubulin (tub) and alpha-actin), cellular homeostatic elements (sodium potassium ATPase (NaK-ATPase) and sodium hydrogen exchanger (NHE-1)), and sensory nerve fibres (CGRP) (n=10) for fluorescence microscopy of worn and unworn regions of the mesial cusp. Immunoreactivity (IR) to vim, actin, NaK-ATPase and CGRP was confined to the pulpal third of odontoblast processes (OPs). IR to tub and nhe-1 was expressed by OPs in full dentine thickness. In areas associated with dentine exposure, the tubules contained no OPs. In regions with intact dentine, odontoblasts were arranged in a single cell layer and easily distinguished from the sub-odontoblast cells. In regions with open tubules, the odontoblasts were in stratified or pseudo-stratified in arrangement. Differences in structural antibody expression suggest a previously unreported heterogeneity of the odontoblast population and variations in different regions of the OP. This combined with differences in OPs extension and pulp cellular arrangement in worn and unworn regions suggests active and dynamic cellular responses to the opening of dentinal tubules by tooth wear. PMID- 26547701 TI - Alternative Medicine and Asthma, What Is the Evidence? PMID- 26547700 TI - Antioxidant therapy in the elderly with tinnitus. AB - INTRODUCTION: Several approaches have been tried for the treatment of tinnitus, from cognitive-behavioral therapies and sound enrichment to medication. In this context, antioxidants, widely used in numerous areas of medicine, appear to represent a promising approach for the control of this symptom, which often is poorly controlled. OBJECTIVE: To evaluate the effects of antioxidant therapy for tinnitus in a group of elderly patients. METHODS: Prospective, randomized, double blinded, placebo-controlled clinical trial. The sample consisted of 58 subjects aged 60 years or older, with a complaint of tinnitus associated with sensorineural hearing loss. These individuals completed the Tinnitus Handicap Inventory (THI) questionnaire before and after six months of therapy. The treatment regimens were: Ginkgo biloba dry extract (120mg/day), alpha-lipoic acid (60mg/day)+vitamin C (600mg/day), papaverine hydrochloride (100mg/day)+vitamin E (400mg/day), and placebo. RESULTS: There was no statistically significant difference between THI by degree (p=0.441) and by score (p=0.848) before and after treatment. CONCLUSION: There was no benefit from the use of antioxidant agents for tinnitus in this sample. PMID- 26547702 TI - Role of Innate Lymphoid Cells in Lung Disease. AB - Innate lymphoid cells (ILCs) are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th)1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages. Three types of ILCs (ILC1, 2 & 3) have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK) cells and interferon (IFN)-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL 13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis. There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD). Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases. In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD. PMID- 26547703 TI - Identification of Aspergillus (A. flavus and A. niger) Allergens and Heterogeneity of Allergic Patients' IgE Response. AB - Aspergillus species (A. flavus and A. niger) are important sources of inhalant allergens. Current diagnostic modalities employ crude Aspergillus extracts which only indicate the source to which the patient has been sensitized, without identifying the number and type of allergens in crude extracts. We report a study on the identification of major and minor allergens of the two common airborne Aspergillus species and heterogeneity of patients' IgE response to them. Skin prick tests were performed on 300 patients of bronchial asthma and/or allergic rhinitis and 20 healthy volunteers. Allergen specific IgE in patients' sera was estimated by enzyme allergosorbent test (EAST). Immunoblots were performed to identify major/minor allergens of Aspergillus extracts and to study heterogeneity of patients'IgE response to them. Positive cutaneous responses were observed in 17% and 14.7% of patients with A. flavus and A. niger extracts, respectively. Corresponding EAST positivity was 69.2% and 68.7%. In immunoblots, 5 allergenic proteins were identified in A. niger extract, major allergens being 49, 55.4 and 81.5 kDa. Twelve proteins bound patients' IgE in A. flavus extract, three being major allergens (13.3, 34 and 37 kDa). The position and slopes of EAST binding and inhibition curves obtained with individual sera varied from patient to patient. The number and molecular weight of IgE-binding proteins in both the Aspergillus extracts varied among patients. These results gave evidence of heterogeneity of patients' IgE response to major/minor Aspergillus allergens. This approach will be helpful to identify disease eliciting molecules in the individual patients (component resolved diagnosis) and may improve allergen specific immunotherapy. PMID- 26547704 TI - Molecular Cloning and Expression of a New Allergen of Acacia farnesiana (Aca f 2). AB - Inhalation of pollens from different species of Acacia is a common cause of respiratory allergy in tropical areas of the world. Acacia farnesiana is commonly used as street trees in towns and ornamental shade trees in parks and gardens throughout arid and semi-arid regions of Asia. This study aimed to produce and purify the A. farnesiana pollen profilin (Aca f 2) and evaluate its nucleotide sequence homology with profilins of common allergenic plants to predict allergenic cross-reactivity. Thirty-nine patients who were allergic to Acacia pollens were included in the study. Cloning of Acacia profilin-coding sequence was performed by polymerase chain reaction using primers from Acacia pollen RNA. The cDNA of Acacia pollen profilin was then expressed in Escherichia coli using pET-21b(+) vector and purified by metal affinity chromatography. Immunoreactivity of the recombinant Acacia profilin (rAca f 2) was evaluated by specific ELISA, immunoblotting, and inhibition assays. The coding sequence of the Acacia profilin cDNA was recognized as a 399-bp open reading frame encoding 133 amino acid residues. Eighteen patients (18/39, 46.15%) had significant specific IgE levels against Aca f 2. Immunodetection and inhibition assays indicated that purified Aca f 2 might be the same as that in the crude extract. Aca f2, the first allergen from A. farnesiana pollen, was identified as belonging to the family of profilins. The amino acid sequence homology analysis showed high cross-reactivity between Aca f 2 and other profilins from botanically unrelated common allergenic plants. PMID- 26547705 TI - Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4 Producing CD8+ T Cells in Patients with Allergic Asthma. AB - Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-gamma, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-gamma levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID- 26547706 TI - Association between Interleukin-23 Receptor R381Q Gene. AB - The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma. PMID- 26547707 TI - Effect of Influenza Virus Infection in a Murine Model of Asthma. AB - Respiratory virus infection is a major cause of asthma exacerbation. However, the underlying mechanisms of this exacerbation are unknown. Therefore, to determine the mechanisms, we examined the effect of influenza infection in a murine model of asthma. Mice were divided into four groups: the phosphate-buffered saline (PBS), house dust mite(HDM), influenza, and HDM/influenza groups. The influenza group and the HDM/influenza group were infected with influenza A virus. We measured airway resistance (Penh value), examined the lung tissue for pathology, and analyzed the cells and cytokines in bronchoalveolar lavage fluid (BALF) by ELISA. At 50 mg/mL methacholine, the HDM/influenza group showed a significantly higher Penh value than the PBS, HDM, and influenza groups. The number of neutrophils in BALF was higher in the HDM/influenza group than in the HDM group. A significantly greater number of lymphocytes and macrophages were detected in the HDM/influenza group than in the HDM group. IFN-gamma and IL-1beta levels were higher in the HDM/influenza group than in the HDM group. IL-5 levels did not vary between the HDM and HDM/influenza groups, IL-10 was significantly lower in the HDM/influenza than in the HDM group. Chemokine (C-X-C motif) ligand 1 (CXCL1) and regulated upon activation, normal T cell expressed and secreted (RANTES) were higher in the HDM/influenza group than in the HDM group. In a murine model of asthma, influenza-induced airway inflammation appeared to be caused by simultaneous activation of neutrophilic and eosinophilic inflammation. PMID- 26547708 TI - The Effect of Preventive Immunization on the Incidence of Allergic Conditions. AB - The purpose of this study was to assess the effect of preventive immunization on the incidence of allergies in Poland. 18,617 (53.8% female, 24.2% 6-7 years old, 25.4% 13-14 years old, 50.4% 20-44 years old) were selected by stratified cluster sampling method in 8 cities and 1 rural area. 4783 of whom underwent objective outpatient screening assessments. Study subjects were evaluated for any association between preventive immunization against rubella, measles, typhoid fever, smallpox and incidence of atopic dermatitis, allergic rhinitis, and asthma. There was no increased risk of allergy incidence in the majority of vaccinated subjects against rubella, measles, typhoid fever, or smallpox (OR from 0.42 (p<0.0001) to 1.34 (p<0.0001) with 95% CI from 0.27-0.65 to 1.19-1.50). Slightly increased risk of asthma was after vaccination against typhoid (OR=1.27; p<0.0001) and smallpox (OR=1.21; p=0.02). The risk of atopic dermatitis (AD) was also evaluated following vaccination against rubella (OR=1.34; p<0.0001), typhoid (OR=1.13; p=0.005), varicella (OR=1.18; p=0.003); rhinitis and AR following vaccination against measles (respectively OR=1.22; p<0.0005 and OR =1.21; p=0.0002). No higher risk of allergic diseases was demonstrated in vaccinated individuals diagnosed by doctor in an outpatient setting. These data do not demonstrate a causal relationship between vaccinations and allergic conditions. PMID- 26547709 TI - High Usage of Complementary and Alternative Medicine among Turkish Asthmatic Children. AB - An increasing number of asthmatic patients are attracted by complementary and and alternative medicine (CAM). The aim of this study was to estimate the prevalence and describe the characteristics of CAM use by children with asthma in a paediatric allergy clinic in Istanbul, Turkey. The parents of asthmatic children were invited to participate in a cross-sectional survey study. Current asthma treatment, severity of asthma, emergency admittances and hospitalisations, education of parents, settlements, income of the family and parental use of CAM were investigated as predictors of CAM usage. Out of the 500 patients, 330 (66%) had used CAM therapy; most popular modalities were herbal medicine (45%), honey (41.6%), grape syrup (37.2%) and quail eggs (36.2%). The most common used herbal medicine in the study group were linden (21.6%) and ginger (21.2%). There was no significant difference in regard to the use of regular asthma treatment, the severity of asthma, the frequency of emergency admittance, hospitalisations due to asthma, education of parents and settlements between CAM users and non-CAM group. A significant inverse association was found in terms of family income and CAM usage. Parents' own use of CAM was also associated with significant increase in the use of CAM. In conclusion; the prevalance of reported CAM use among Turkish asthmatic children was found to be high (66%), with herbal medicine being the most popular modality. The results of this study shows that CAM use becomes more prevelant among asthmatic children from families with low income. It will be increasingly important for physicians who care for allergic children to be aware of high CAM usage. PMID- 26547710 TI - In Vitro Generation of IL-35-expressing Human Wharton's Jelly-derived Mesenchymal Stem Cells Using Lentiviral Vector. AB - Human Wharton's Jelly-derived Mesenchymal Stem Cells (hWJ-MSCs) are easily available cells without transplant rejection problems or ethical concerns compared to bone-marrow-derived MSCs for prospective clinical applications. These cells display immunosuppressive properties and may be able to play an important role in autoimmune disorders. Regulatory T-cells (Treg) are important to prevent autoimmune disease development. Interleukin 35 (IL-35) induces the proliferation of Treg cell populations and reduces the activity of T helper 17 (Th17) and T helper 1 (Th1) cells, which play a central role in initiation of inflammation and autoimmune disease. Recent studies identified IL-35 as a new inhibitory cytokine required for the suppressive function of Treg cells. We created IL-35-producing hWJ-MSCs as a good vehicle for reduction of inflammation and autoimmune diseases. We isolated hWJ-MSCs based on explant culture. HWJ-MSCs were transduced at MOI=50 (Multiplicity of Infection) with lentiviral particles harboring murine Interleukin 35 (mIL-35). Expression of IL-35 in hWJ-MSCs was quantified by an IL 35 ELISA kit. IL-35 bioactivity was analyzed by inhibiting the proliferation of mouse splenocytes using CFSE cell proliferation kit. Frequency of CD4+CD25+CD127 low/neg Foxp3+ Treg cells was measured by flow cytometry. There was an up to 85% GFP positive transduction rate, and the cells successfully released a high level of mIL-35 protein (750 ng/ml). IL-35 managed to inhibit CD4+ T cell proliferation with PHA, and improved the frequency of Treg cells. Our data suggest that transduced hWJ-MSCs overexpressing IL-35 may provide a useful approach for basic research on gene therapy for autoimmune disorders. PMID- 26547711 TI - Constructing Chimeric Antigen for Precise Screening of HTLV-I Infection. AB - Individual preparation of two human T-cell lymphotropic virus type I (HTLV-I) diagnostic GST fused peptides (MTA-1 and GD21) is time-consuming and expensive. The aim of this study was to design a novel single chimeric antigen (SCA) to obviate separate expression of proteins and reduce the cost of reagent preparation. Structural protein fragments, including immunodominant B cell linear epitopes, were selected and different SCAs were designed. Tertiary structure, epitope exposure, solubility and stability were calculated for each SCA and compared with each other. The synthetic DNA encoding the interested SCA was sub cloned into pET32a expression vector, expressed as a soluble form in Escherichia coli BL21 (DE3) cells and purified under native condition using affinity chromatography. The SDS-PAGE results indicated that thioredoxin-fused SCA was successfully expressed as a soluble form in E. coli BL21 (DE3) cells. The results of ELISA confirmed that SCA reacted with anti-HTLV-I antibodies in a concentration-dependent manner. Our results indicated that the designed SCA may be a good candidate for the screening of HTLV-I carriers with antigen-antibody based tests. PMID- 26547713 TI - Polymorphism in the IL-8 Gene Promoter and the Risk of Acne Vulgaris in a Pakistani Population. AB - Interleukin-8 (IL-8) is a well-known inflammatory chemokine and suggested to be involved in the development of acne vulgaris. This study investigates IL-8 plasma levels in acne patients and healthy controls and the molecular basis for the regulation of the IL-8 gene in a Pakistani population. Patients with acne vulgaris (n = 264) and healthy individuals (n = 264) were enrolled in this investigation. Plasma IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA). The genotyping for IL-8 gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Our data showed a statistically significant increase in IL-8 levels from acne patients compared with healthy subjects (154.2 +/- 52.1 pg/mL in patients vs. 101.6 +/- 33.5 pg/mL in controls, p<0.0001). The IL-8-251T>A (rs4073) polymorphism was significantly higher in patients with acne compared with the control group (p=0.013). There was a significant difference between the T and A alleles from acne cases and controls (odds ratio OR=1.6,95 % CI= 1.16-2.19, p=0.003). Logistic regression analysis showed that the increased IL-8 levels, and the IL-8-251T>A polymorphism were significantly associated with acne. Our data suggest that the elevated IL-8 levels and the IL-8-251T>A polymorphism may be associated with acne vulgaris in the study population. PMID- 26547712 TI - Single Nucleotide Polymorphism rs 2476601 of PTPN22 Gene and Susceptibility to Rheumatoid Arthritis in Iranian Population. AB - The rs2476601 (R620W, C1858T) polymorphism in PTPN22 gene has been repeatedly reported to be associated with rheumatoid arthritis (RA). The rs 2476601 is widely suggested for predictive testing and risk assessment for RA. The aim of this study was to test the possible association of this SNP with RA in Iranian population. A total of 872 samples (405 confirmed RA patients and 467 healthy controls) were recruited in this study. Genomic DNA was extracted from whole blood and the genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Genotyping for a set of samples were re confirmed by two other rounds of genotyping, using another PCR-RFLP experiment with different enzyme and DNA sequencing. All 872 samples were genotyped as homozygous CC in first round of genotyping. Genotyping was repeated for 30% of samples by another restriction enzyme and for 10% of samples by sequencing. Again all samples showed homozygous CC genotype. This study suggests that the rs2476601 polymorphism of PTPN22 gene is mono-morphic in Iranian population, containing only C allele. Considering that previous studies in other populations reported the T allele as the risk allele at this locus, the present study concluded that rs2476601 play no role in susceptibility to RA and other autoimmune diseases in Iranian population. This finding has significant future clinical implications in determining the strategy for risk assessment and predictive testing for such diseases in Iranian population. PMID- 26547714 TI - Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria. AB - We aimed to investigate IgG antibody levels specific to Toxocara canis (T. canis), a parasite which subsists in dog's intestine, on serum samples obtained from patients with chronic urticaria (CU) to evaluate effective risk in CU etiopathogenesis. In this study, 73 patients diagnosed with CU and 109 healthy individuals as control group, were included. Various factors such as sex, age, education and income, daily hand washing habits, history of dog owning and soil eating were questioned in patient anamnesis. T. canis IgG antibodies were detected using an enzyme linked immunosorbent assay (ELISA) kit prepared with T. canis larval excretory-secretory antigens. Positive results were confirmed with western blot (WB) WB test. We found T. canis IgG positivity in 17.8% (n=13) of patients (n=73) with CU. But we did not observe any T. canis IgG positivity in healthy controls (n=109). Low molecular weight bands (24-35 kDa) were observed in 11 samples in WB analyses while two of the samples were weakly positive. It is revealed that dog owning history increases T. canis seropositivity 12.9 times while insufficient daily hand washing habit (less than six times a day) increases seropositivity 20.7 times. Our study showed that T. canis may trigger CU since we found 17.8% seropositivity in 73 patients with CU and none in 109 healthy individuals. Moreover, various socio-demographic characteristics have been shown to affect T. canis seropositivity in patients with CU. PMID- 26547715 TI - A New IL-2RG Gene Mutation in an X-linked SCID Identified through TREC/KREC Screening: a Case Report. AB - Severe combined immunodeficiency (SCID) represents a rare group of primary immunodeficiency disorders (PIDs), with known or unknown genetic alterations. Here, we report a new interleukin 2 receptor, gamma chain (IL-2RG) mutation in an Iranian SCID newborn. The patient was a 6-day old boy with a family history of PID. The child was screened using a molecular-based analysis for the assessment of T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). Moreover, a complete immunological evaluation and gene sequencing was performed. Results showed undetectable TREC but a high level of KREC copy numbers. Flow cytometric data indicated low numbers of T and NK cells, but elevated number of B cells. A novel substitution in IL2RG: c.675 C>A, leading to p.225 Ser>Arg was found. Based on the functional analysis, the mutation is predicted to be damaging. The patient was diagnosed as a T B+ NK X-linked SCID. PMID- 26547716 TI - Similarities and Differences in Sexual Risk Behaviors Between Young Black MSM Who Do and Do Not Have Sex with Females. AB - The objective of this study is to determine whether young Black MSM who also have sex with females report similar levels of sexual risk behaviors as those not having sex with females. YBMSM (N = 400) were recruited from an STI clinic, located in the Southern U.S. Men completed an audio-computer assisted self interview and donated specimens for STI/HIV testing. Forty-three percent recently engaged in penile-vaginal sex. They were less likely to report having concurrent partners (P = .01), unprotected fellatio (P = .04), multiple partners as a bottom (P < .02), any unprotected anal sex as a bottom (P < .013), and any anal sex (P = .007). They were equally likely to report favorable attitudes toward serosorting (P = .80), multiple male partners as a top (P = .20), unprotected anal insertive sex with males (P = .15). Frequency of sex with males as a top (P = .61) or bottom (P = .61) did not differ. Compared to YBMSM not having sex with females, those having sex with females may be exercising greater caution. PMID- 26547717 TI - Notochord manipulation does not impact oesophageal and tracheal formation from isolated foregut in 3D explant culture. AB - BACKGROUND: Tracheo-oesophageal malformations result from disturbed foregut separation during early development. The notochord, a specialised embryonic structure, forms immediately adjacent to the dividing foregut. In the Adriamycin mouse model of oesophageal atresia, foregut and notochord abnormalities co-exist, and the site and severity of foregut malformations closely correlate to the position and extent of the notochord defects. Notochord and foregut abnormalities also co-exist in the Noggin Knockout mouse as well in a small number of human cases. The notochord is a source of powerful molecular signals during early embryogenesis, being particularly important for neural crest development. The influence of notochord signaling on the adjacent foregut is not known. The purpose of this study was to examine the impact of notochord manipulation on foregut separation using a robust 3D explant method for culturing isolated foregut which permits oeosphageal and tracheal formation in vitro. METHODS: Foregut was micro-dissected from embryonic day 9 mice (License B100/4447 Irish Medicines Board), embedded in collagen and cultured for 48 h with native notochord intact (n = 6), notochord removed (n = 10) or additional notochord transplanted from stage matched controls (n = 8). Specimens were analysed for foregut morphology and molecular patterning using immunohistochemistry for Hnf3b (an endoderm marker) and Sox2 (a notochord and oesophageal marker) on cryosections. RESULTS: Foregut separation into distinct oesophagus and trachea was observed in isolated foregut specimens with or without their native notochord. In specimens with additional notochord transplants, foregut morphology and molecular patterning were comparable to controls whether or not the native notochord was maintained. In particular foregut separation was not disrupted by the transplantation of additional notochord at the dorsal foregut endoderm. CONCLUSION: The relationship between the embryonic foregut and notochord is complex and ill-defined; however, the notochord does not contribute essentially to oesophagus and trachea formation beyond E9 in the mouse, and the transplantation of additional notochord does not disrupt foregut separation in 3D explant culture. PMID- 26547718 TI - Consumer Understanding, Preferences, and Responses to Different Versions of Drug Safety Messages in the United States: A Randomized Controlled Trial. AB - INTRODUCTION: As part of its mission, the US Food and Drug Administration (FDA) communicates with the public regularly about the benefits and risks of prescription and over-the-counter (OTC) drugs. Effectively communicating risk, however, is a significant public health challenge. OBJECTIVE: To better understand how different populations understand information communicated by the FDA about drug safety, we conducted a randomized experiment to examine comprehension and other measures of effectiveness of drug safety messages that occurred in a post-market surveillance phase. METHODS: We used an Internet panel survey of 1244 consumers, of whom 58% used prescription drugs in the past year. Half of the sample panel was randomized to read a previous FDA Drug Safety Communication (DSC) with the drug name changed, and the other half was randomized to read a revised version of the same DSC. We examined how making certain modifications to the way drug risk information is communicated has an impact on comprehension and behavioral intentions, including the user's likelihood of discontinuing the drug. We also studied how comprehension varied by respondent characteristics, health literacy skills, risk perceptions, and trust in the message. RESULTS: Based on a five-item comprehension index, the revised version of the message was associated with significantly greater comprehension of the information relative to the standard version (63 vs 52% correct, p < 0.001). Significantly more respondents found the revised version to be clear (82 vs 73%, p < 0.000), while fewer in that group reported learning something new (78% vs 84%, p = 0.015). No significant differences emerged between the two groups in terms of the message being informative, convincing, or helpful. We found no significant differences between the two groups in terms of behavioral intentions, risk perception, and trust. CONCLUSIONS: We found that making plain language changes to the DSC significantly increased consumers' level of comprehension of its content, providing support for ongoing use and further exploration of these strategies in pharmacovigilance communication research. The study findings have important implications for future drug safety and other communication messages related to prescription drugs. PMID- 26547719 TI - Adverse Drug Reactions Reported to a National HIV & Tuberculosis Health Care Worker Hotline in South Africa: Description and Prospective Follow-Up of Reports. AB - INTRODUCTION: The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. METHODS: We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. RESULTS: We received 772 ADR reports, of which 87/772 (11.3%) were classified as certain, 176/772 (22.8%) as probable, 361/772 (46.8%) as possible, and 148/772 (19.2%) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6%), 87/624 (13.9%), and 77/624 (12.3%), respectively. The ADR was severe in 27.3% of rashes, 36.4% of kidney injury reports and 88.5% of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3%) improved, 9 (2.3%) had complete resolution, 32 (8.4%) remained unchanged, 6 (1.6%) deteriorated, 10 (2.6%) died and 72 (18.8%) had unknown outcome. Advice provided was followed in 93.2% of these cases. Of 223 ADRs with preventability data, 40 (17.9%) were preventable. CONCLUSION: Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority. PMID- 26547720 TI - Assessment of Apical Extrusion during Root Canal Irrigation with the Novel GentleWave System in a Simulated Apical Environment. AB - INTRODUCTION: This study assessed apical extrusion during treatment with GentleWave (GW; Sonendo Inc, Laguna Hills, CA), a conventional open-ended 30-G needle (CN), or Endovac (EV; SybronEndo, Orange, CA) in root canals enlarged to different dimensions with and without apical constriction. METHODS: Sixteen mandibular molars were mounted in an in vitro apparatus. Roots were immersed in a pressure-regulated chamber containing distilled water with pressure kept at 5.88 +/- 0.15 mm Hg to simulate periapical back pressure. Mesiobuccal (curved <=30 degrees ) and distal (straight) canals were instrumented to the working length (WL) as follows: minimal instrumentation (MI, #15/.04), traditional instrumentation (#35/.06), or overinstrumentation (OI, #35/.06, to the WL + 1 mm). Canals were tested 5 times each with distilled water using GW, CN (at WL-3 mm), or EV and the mass (g) of extruded water recorded. Extrusion frequency and mean extruded mass were compared for each canal, irrigation group, and canal instrumentation mode (Wilcoxon t test, P < .05). RESULTS: No extrusion occurred with GW and EV, whereas the frequency of extrusion with CN was 33%. Mean extruded water mass using CN ranged in mesial canals from 0.000 +/- 0.000 g (OI) to 0.047 +/- 0.098 g (MI) and in distal canals from 0.123 +/- 0.191 g (MI) to 0.505 +/- 0.490 g (OI). With traditional instrumentation and OI instrumentation, extruded mass in distal canals was significantly higher than in mesial canals (P < .002) and distal canals with MI (P < .020). CONCLUSIONS: Within this study's limitations, root canal treatment with GW and irrigation with EV was not associated with extrusion. Extruded irrigation mass using the open-ended 30-G needle depended on the canal type and enlargement. These results have to be interpreted with caution, and further investigations are warranted to evaluate the possibility of extrusion using GW in different tooth types and clinical situations. PMID- 26547721 TI - Pathway-based variant enrichment analysis on the example of dilated cardiomyopathy. AB - Genome-wide association (GWA) studies have significantly contributed to the understanding of human genetic variation and its impact on clinical traits. Frequently only a limited number of highly significant associations were considered as biologically relevant. Increasingly, network analysis of affected genes is used to explore the potential role of the genetic background on disease mechanisms. Instead of first determining affected genes or calculating scores for genes and performing pathway analysis on the gene level, we integrated both steps and directly calculated enrichment on the genetic variant level. The respective approach has been tested on dilated cardiomyopathy (DCM) GWA data as showcase. To compute significance values, 5000 permutation tests were carried out and p values were adjusted for multiple testing. For 282 KEGG pathways, we computed variant enrichment scores and significance values. Of these, 65 were significant. Surprisingly, we discovered the "nucleotide excision repair" and "tuberculosis" pathways to be most significantly associated with DCM (p = 10(-9)). The latter pathway is driven by genes of the HLA-D antigen group, a finding that closely resembles previous discoveries made by expression quantitative trait locus analysis in the context of DCM-GWA. Next, we implemented a sub-network-based analysis, which searches for affected parts of KEGG, however, independent on the pre-defined pathways. Here, proteins of the contractile apparatus of cardiac cells as well as the FAS sub-network were found to be affected by common polymorphisms in DCM. In this work, we performed enrichment analysis directly on variants, leveraging the potential to discover biological information in thousands of published GWA studies. The applied approach is cutoff free and considers a ranked list of genetic variants as input. PMID- 26547724 TI - Discussion. PMID- 26547722 TI - The diagnostic value of [(18)F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection. AB - PURPOSE: The diagnosis of osteomyelitis and implant-associated infections in patients with nonspecific laboratory or radiological findings is often unsatisfactory. We retrospectively evaluated the contributions of [(18)F]FDG PET and [(18)F]FDG PET/CT to the diagnosis of osteomyelitis and implant-associated infections, enabling timely and appropriate decision-making for further therapy options. METHODS: [(18)F]FDG PET or PET/CT was performed in 215 patients with suspected osteomyelitis or implant-associated infections between 2000 and 2013. We assessed the diagnostic accuracy of both modalities together and separately with reference to intraoperative microbial findings, with a mean clinical follow up of 69 +/- 49 months. RESULTS: Infections were diagnosed clinically in 101 of the 215 patients. PET and PET/CT scans revealed 87 true-positive, 76 true negative, 38 false-positive, and 14 false-negative results, indicating a sensitivity of 86 %, a specificity of 67 %, a positive predictive value (PPV) of 70 %, a negative predictive value (NPV) of 84 % and an accuracy of 76 %. The sensitivity of PET/CT was 88 %, but specificity, PPV, NPV and accuracy (76 %, 76 %, 89 % and 82 %, respectively) were higher than those of stand-alone PET. CONCLUSION: [(18)F]FDG PET is able to identify with high sensitivity the presence of osteomyelitis in orthopaedic surgery patients with nonspecific clinical symptoms of infection. PMID- 26547725 TI - Reply to: Social media and surgery: An alternative view. PMID- 26547726 TI - Resection versus expectant management of small incidentally discovered nonfunctional pancreatic neuroendocrine tumors. AB - BACKGROUND: Sporadic, nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) are diagnosed with increasing frequency. We compared the risk of tumor growth, metastasis, and mortality between patients treated versus those treated expectantly. METHOD: A retrospective study of patients seen at our institution with sporadic NF-PNETs, with >= 12 months of follow-up. Kaplan-Meier analysis was performed. RESULTS: Between 1999 and 2014, 35 patients with an incidentally discovered nonfunctional PNET were identified. Twenty underwent resection and 15 were followed with imaging. In the operative group, 8 had NF-PNETs < 2 cm, while 12 had NF-PNETs >= 2 cm. In the nonoperative expectant management by serial imaging group, 10 had NF-PNETs < 2 cm while 5 had NF-PNETs >= 2 cm. Small NF PNETs (<2 cm) in either the operative or nonoperative groups demonstrated no evidence of progression or metastasis (median follow-up of 27.8 months). Morbidity in the operative group was 35% with pancreatic pseudocyst the most common. CONCLUSION: Incidentally discovered NF-PNETs < 2 cm in size can be observed safely with serial imaging. PMID- 26547727 TI - Quality of life and independent living and working levels of farmers and ranchers with disabilities. AB - BACKGROUND: The status of farmers and ranchers with disabilities has been understudied. Understanding this population's quality of life (QOL) and independent living and working (ILW) levels have the potential to be informative for changes in public policy and service provision. OBJECTIVE: To assess QOL levels among farmers and ranchers with disabilities as well as explore a conceptual model of ILW accounting for variance in QOL levels. METHODS: Participants (N = 398) included farmers and ranchers with varying disabilities. Descriptive information was gathered using the McGill Quality of Life (MQOL) and ILW measures. The MQOL measure produces an objective and comprehensive profile of one's QOL across several domains. ILW was used to account for variance in QOL scores. We also examined whether there were any differences in QOL and or ILW based on type of disability. RESULTS: There were no differences in type of disability and QOL levels. The mean QOL level was 5.50 (SD = 1.67; N = 398). The sample rated support and existential well-being the highest among the QOL subscales, which confounds previous research. Further, age group and ILW accounted for 16.2% of the variance in QOL levels, P < .001. CONCLUSIONS: With this sample of farmers and ranchers with disabilities, age group and ILW account for significant variance in QOL. Health professionals can use these findings to support and assess improvements in clients' ILW, self-determination, and QOL. Future research is needed to explore further the effects of QOL and ILW in this population. PMID- 26547728 TI - Freedom from reoperation 38 years after a ross procedure performed in middle age- what can we learn from this remarkable survival? PMID- 26547729 TI - Long-term course of a patient with congenital corrected transposition of the great arteries and dextrocardia--The Fisher King. PMID- 26547730 TI - Red blood cell distribution width: Just one of many things to consider. PMID- 26547731 TI - Acute myocardial injury during strenuous physical activity. PMID- 26547732 TI - Sedentary behavior and predicted 10-yr risk for a first atherosclerotic cardiovascular disease (ASCVD) event using the pooled cohort risk equations among US adults. PMID- 26547733 TI - Comments on Li et al. HbA1c and all-cause mortality risk among patients with type 2 diabetes. International Journal of Cardiology. 2015; 202:490-496. PMID- 26547734 TI - Takotsubo cardiomyopathy and pheochromocytoma: "What therefore God hath joined together, let not man put asunder". PMID- 26547735 TI - Rare and life-threatening cardiovascular complication of chronic thromboembolic pulmonary hypertension diagnosed by trans-thoracic echocardiography. PMID- 26547736 TI - aVR and attenuation of the amplitude of the QRS complexes by comparing 2 electrocardiograms in the differentiation of takotsubo syndrome and anterior ST elevation myocardial infarction. PMID- 26547737 TI - Focus on direct oral anticoagulants (DOAC) for prophylaxis of venous thrombosis and pulmonary embolism in medically ill patients. PMID- 26547738 TI - The potential role of TLR4/caveolin-1/NOS pathway in oxyLDL-modulation of autophagic/apoptotic responses in endothelial cells. PMID- 26547739 TI - Native T1 in deciphering the reversible myocardial inflammation in cardiac sarcoidosis with anti-inflammatory treatment. PMID- 26547740 TI - Myocardial infarction precipitating Takotsubo cardiomyopathy. PMID- 26547741 TI - Screening for atrial fibrillation with automated blood pressure measurement: Research evidence and practice recommendations. AB - Several guidelines recommend opportunistic screening for atrial fibrillation (AF) in subjects aged >= 65 years using pulse palpation during routine blood pressure (BP) measurement. However, this method has limited diagnostic accuracy. A specific algorithm for AF detection during automated BP measurement was developed and implemented in a novel oscillometric device (Microlife WatchBP Home-A). In 2013, the UK National Institute for Health and Care Excellence (NICE) recommended this device for AF screening during routine office BP measurement in primary care in subjects >= 65 years. A review and meta-analysis of the evidence on the diagnostic accuracy of this algorithm were performed. Six studies (n=2332) investigated the accuracy of AF detection using the Microlife BP monitor and estimated a pooled sensitivity at 0.98 (95% CI 0.95, 1.00) and specificity 0.92 (0.88, 0.96). Analysis of 4 studies (n=1126) showed more readings to improve specificity (from 0.86 to 0.91) and sensitivity (from 0.97 to 0.99). Taking 3 sequential readings with at least 2 detecting AF gave the highest diagnostic accuracy. A single study (n=139) of paroxysmal AF screening with home BP monitoring (3316 days) showed sensitivity 99% and specificity 93%. Another study (n=46) of AF screening with 24h ambulatory BP monitoring showed that AF detected in >15% of all readings has high probability of AF diagnosis requiring confirmation by 24h electrocardiography. AF detection with routine automated BP measurement is a reliable screening tool in the elderly, which requires confirmation by electrocardiography. Paroxysmal AF might also be detected by routine automated home or ambulatory BP monitoring. PMID- 26547742 TI - A long-term follow-up of patients with prolonged asystole of greater than 15s on head-up tilt testing. AB - BACKGROUND: Head-up tilt (HUT) is used for diagnosis of vasovagal syncope (VVS), and can provoke cardioinhibition. VVS is usually considered benign, however pacemaker insertion may be indicated in some patients. We sought to characterize the long-term outcomes of patients with prolonged asystole (>15s) on HUT. METHODS: We conducted a retrospective study on patients with asystole >15s on HUT identified from 5133 patients who were investigated between 1998 and 2012 at our institution. Patients were mailed questionnaires or telephoned to ascertain outcomes. Where contact was not possible, the patients' general practitioners were contacted to request up-to-date information. RESULTS: A total of 26 patients with a mean age of 45 +/- 18 years and a mean duration of asystole on HUT of 26 +/- 7s were successfully followed up from a total of 77 patients identified. The follow-up duration was 99 +/- 39 months. Six patients had undergone pacemaker (PPM) implantation. Of the patients without PPM, 16 reported spontaneously improved symptoms. Ten patients sustained injury prior to HUT compared with one after HUT, when a clear diagnosis was made and management advice was given. There were no major injuries or deaths after HUT. The 6 patients with PPMs had a mean age of 60 +/- 16 (67% male) at HUT. Four patients had no further syncope after PPM and two demonstrated improvement but still experienced recurrent syncope. CONCLUSIONS: Prolonged asystole (>15s) on tilt does not necessarily predict adverse outcomes with most patients improving spontaneously over the long-term. Pacemaker insertion in selected patients may reduce syncope recurrence but does not always abolish it. PMID- 26547743 TI - Anabolic-androgenic steroids and athlete's heart: When big is not beautiful....! PMID- 26547744 TI - Acute myocardial infarction in a 39-year-old lactating woman. PMID- 26547745 TI - Evaluation of the learning curve for transcatheter aortic valve implantation via the transfemoral approach. AB - BACKGROUND: The aim of this study was to evaluate the learning curve in performing transfemoral TAVI (TF-TAVI). METHODS: Between October 2006 and October 2013, 312 consecutive TF-TAVI cases performed by 6 interventional cardiologists, using the Edwards Sapien valve and 104 using the CoreValve, were included in the present analysis. Cumulative sum (CUSUM) failure analysis of combined 30-day safety endpoint was used to evaluate learning curves. RESULTS: The CUSUM analysis revealed a learning curve regarding the occurrence of 30-day adverse events with an improvement after the initial 86 cases using the Edwards valve and 40 cases using the CoreValve. We divided the Edwards valve cases into two groups (early experience: Cases 1 to 86; late experience: Cases 87 to 312). The rate of 30-day mortality and 1-year mortality significantly decreased in the late experience group (17% to 7%, p=0.019; 34% to 21%, p=0.035, respectively). We divided the CoreValve cases into two groups (early experience: Cases 1 to 40; late experience: Cases 41 to 104). The rate of 30-day mortality and 1-year mortality significantly decreased in the late experience group (20% to 6%, p=0.033; 38% to 15%, p=0.040, respectively). The groups including both valves were also analyzed after propensity-matching (early [n=52] vs late [n=52]). This model also showed that 30-day and 1-year mortality rates were significantly lower in the late experience group (13% to 1%, p=0.028; 34% to 20%, p=0.042, respectively). CONCLUSIONS: An appropriate level of experience is needed to reduce the complication rate and mortality in TF-TAVI. PMID- 26547746 TI - Improved Surgical Success of Combined Glaucoma Tube Shunt and Retisert((r)) Implantation in Uveitic Eyes: A Retrospective Study. AB - INTRODUCTION: The purpose of this study was to determine whether the outcomes following placement of a fluocinolone acetonide implant (Retisert((r)); Bausch & Lomb, Inc.) combined with an AhmedTM glaucoma valve (New World Medical, Inc.) in eyes with uveitic glaucoma (UG Retisert) were different when compared to an Ahmed valve alone in eyes with uveitic glaucoma or primary open angle glaucoma (UG non Retisert and POAG, respectively). METHODS: Retrospective, interventional study of consecutive uveitic and OAG eyes undergoing Ahmed valve (AV) implantation with or without combined Retisert insertion at a single academic center between 2009 and 2012. Surgical success was defined as intraocular pressure (IOP) between 5 and 18 mmHg and greater than 20% reduction of IOP at two consecutive visits without need for additional IOP-lowering medications or surgical procedures. Secondary outcome measures included IOP and number of glaucoma medications. RESULTS: Sixty eyes of 60 patients (22 UG Retisert, 16 UG non-Retisert, 22 POAG) were included. Mean +/- standard deviation surgical success duration was significantly greater in UG Retisert eyes, 629 +/- 53 days, compared to those with UG non-Retisert, 361 +/- 37 days, and POAG, 472 +/- 65 days (P = 0.034). At 24 months, the mean IOP was 11.7, 12.1, and 15.0 mmHg and the average patient was on 1.45, 0.71, and 2.00 medications in the UG Retisert, UG non-Retisert, and POAG valve groups, respectively. CONCLUSION: Retisert implants when combined with AV in uveitic glaucoma had a longer duration of surgical success than uveitic or POAG treated with AV insertion alone. PMID- 26547747 TI - Galactosylation of steroidal saponins by beta-galactosidase from Lactobacillus bulgaricus L3. AB - The galactosylation of furostanosides and spirostanosides were investigated by using beta-galactosidase from Lactobacillus bulgaricus L3 as a catalyst and lactose as a sugar donor. Four novel galactosylated furostanoside products (compounds 1-4) from compound F, compound G, compound I, and compound H were obtained and their structures were identified by HR-ESI-MS, 1D and 2D NMR spectra. The result showed that galactosyl moiety was found to be added to the 6 OH of the 26-O-glucosyl in these four furostanoside substrates. PMID- 26547748 TI - Metal ion-promoted cleavage of nucleoside diphosphosugars: a model for reactions of phosphodiester bonds in carbohydrates. AB - Cleavage of five different nucleoside diphosphosugars has been studied in the presence of Cu(2+) and Zn(2+) complexes. The results show that metal ion catalysts promote the cleavage via intramolecular transesterification whenever a neighbouring HO group can adopt a cis-orientation with respect to the phosphate. The HO group attacks the phosphate and two monophosphate products are formed. If such a nucleophile is not available, Cu(2+) complexes are able to promote a nucleophilic attack of an external nucleophile, e.g. a water molecule or metal ion coordinated HO ligand, on phosphate. With the Zn(2+) complex, this was not observed. PMID- 26547750 TI - Determination of glycosylated hemoglobin during hospitalization as an opportunity to assess and optimize glycemic control in our patients: An unresolved matter. PMID- 26547749 TI - SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex. AB - The search for novel anticancer therapeutic agents is an urgent and important issue in medicinal chemistry. Here, we report on the biological activity of the copper-based bioinorganic complex Cu4 (2,4-di-tert-butyl-6-(1H-imidazo- [1, 10] phenanthrolin-2-yl)phenol)4].10 CH3CN (2), which was tested in rat L6 myotubes, mouse NSC-34 motor neurone-like cells, and HepG-2 human liver carcinoma. Upon 96 h incubation, 2 exhibited a significant cytotoxic effect on all three types of cells via activation of two cell death mechanisms (apoptosis and necrosis). Complex 2 exhibited better potency and efficacy than the canonical cytotoxic drug cisplatin. Moreover, during shorter incubations, complex 2 demonstrated a significant SOD mimetic activity, and it was more effective and more potent than the well-known SOD mimetic TEMPOL. In addition, complex 2 was able to interact with DNA and, cleave DNA in the presence of sodium ascorbate. This study shows the potential of using polynuclear redox active compounds for developing novel anticancer drugs through SOD-mimetic redox pathways. PMID- 26547751 TI - Discharge communication is an important underestimated problem in emergency department. PMID- 26547752 TI - Fate of low arsenic concentrations during full-scale aeration and rapid filtration. AB - In the Netherlands, groundwater treatment commonly consists of aeration, with subsequent sand filtration without using chemical oxidants like chlorine. With arsenic (As) concentrations well below the actual guidelines of 10 MUg As/L, groundwater treatment plants have been exclusively designed for the removal of iron (Fe), manganese and ammonium. The aim of this study was to investigate the As removal capacity at three of these groundwater treatment plants (10-26 MUg As/L) in order to identify operational parameters that can contribute to lowering the filtrate As concentration to <1 MUg/L. For this purpose a sampling campaign and experiments with supernatant water and hydrous ferric oxide (HFO) flocs were executed to identify the key mechanisms controlling As removal. Results showed that after aeration, As largely remained mobile in the supernatant water; even during extended residence times only 20-48% removal was achieved (with 1.4-4.2 mg/L precipitated Fe(II)). Speciation showed that the mobile As was in the reduced As(III) form, whereas, As(V) was readily adsorbed to the formed HFO flocs. In the filter bed, the remaining As(III) completely oxidized within 2 min of residence time and As removal efficiencies increased to 48-90%. Filter grain coating analysis showed the presence of manganese at all three treatment plants. It is hypothesized that these manganese oxides are responsible for the accelerated As(III) oxidation in the filter bed, leading to an increased removal capacity. In addition, pH adjustment from 7.8 to 7.0 has been found to improve the capacity for As(V) uptake by the HFO flocs in the filter bed. The overall conclusion is, that during groundwater treatment, the filter bed is crucial for rapid As(III) removal, indicating the importance to control the oxidation sequence of Fe and As for improved As removal efficiencies. PMID- 26547753 TI - Minimally Invasive Management of Complicated Diverticular Disease: Current Status and Review of Literature. AB - BACKGROUND: Diverticulitis is a common condition which carries significant morbidity and socioeconomic burden (McGillicuddy et al in Arch Surg 144:1157 1162, 2009). The surgical management of diverticulitis has undergone significant changes in recent years. This article reviews the role of minimally invasive approach in management of complicated diverticulitis, with a focus on recent concepts and advances. MATERIALS AND METHODS: A literature review of past 10 years (January 2004 to September 2014) was performed using the electronic database MEDLINE from PubMed which included articles only in English. RESULTS: We identified total of 139 articles, out of which 50 were excluded resulting in 89 full-text articles for review 16 retrospective studies, 7 prospective cohorts, 1 case-control series and 1 systematic review were included. These suggest that urgent surgery is performed for those with sepsis and diffuse peritonitis or those who fail to improve despite medical therapy and/or percutaneous drainage. In addition, 3 randomized control trials: DILALA, LapLAND and the Scandinavian Diverticulitis trial are working towards evaluating whether laparoscopic lavage is safe in management of complicated diverticular diseases. Growing trend toward conservative or minimally invasive treatment modality even in severe acute diverticulitis was noticed. CONCLUSIONS: Laparoscopic peritoneal lavage has evolved as a good alternative to invasive surgery, yet clear indications for its role in the management of complicated diverticulitis need to be established. Recent evidence suggests that existing guidelines for optimal management of complicated diverticulitis should be updated. Non-resectional radiographic techniques are likely to play a prominent role in the initial treatment of complicated diverticulitis in the near future. PMID- 26547755 TI - The Lactulose Breath Test in Irritable Bowel Syndrome: Is It All Hot Air? PMID- 26547754 TI - Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma. AB - BACKGROUND: Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. AIM: To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. METHODS: Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. RESULTS: High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival. CONCLUSIONS: Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma. PMID- 26547756 TI - The Density of Interstitial Cells of Cajal Is Diminished in Choledochal Cysts. AB - BACKGROUND AND AIMS: Interstitial cells of Cajal (ICC) have been shown to be present in the extrahepatic biliary tract of animals and humans. However, ICC distribution in choledochal cysts (CC) has not been investigated. A study was conducted to investigate the distribution of ICC in the extrahepatic biliary tract, including CC, in pediatric human specimens. METHOD: The specimens were divided into two main groups as gallbladders and common bile ducts. Gallbladders were obtained from the cholelithiasis, CC operations and autopsies. Common bile ducts were obtained from autopsies. Tissues were stained using c-kit immunohistochemical staining. ICC were assessed semi-quantitatively by applying morphological criteria and were counted as the number of cells/0.24 mm(2) in each area under light microscopy. RESULTS: A total of 35 gallbladders and 14 CC were obtained from operations. Ten gallbladders plus common bile ducts were obtained from autopsies. The mean numbers of ICC in the gallbladders of cholelithiasis and the gallbladders of CC were 12.2 +/- 4.9 and 5.3 +/- 1.2, respectively (p = 0.003). The mean numbers of ICC in the common bile ducts and CC were 9.8 +/- 2.9 and 3.4 +/- 1.4, respectively (p = 0.001). CONCLUSION: The scarcity of ICC in the extrahepatic biliary tract may be responsible for the etiopathogenesis of the CC. PMID- 26547757 TI - Obscure Occult GI Bleeding: An Iatrogenic Tale? PMID- 26547758 TI - From Prague to Seattle: Improved Endoscopic Technique and Reporting Improves Outcomes in Patients with Barrett's Esophagus. PMID- 26547759 TI - The single pile classification: a new tool for the classification of haemorrhoidal disease and the comparison of treatment results. AB - The purpose of the paper is to compare Goligher Classification with the Single Pile Hemorrhoid Classification (SPHC) to show the possible bias and limits of Goligher's use and the possible advantage with the employment of the new classification. SPHC considers the number of pathological piles(N), the characteristics of each internal pile and the characteristics of each external pile, reporting the presence of a fibrous inelastic redundant pile(F), the presence of the subversion of dentate line or the congestion of the external pile(E) and the presence of not tolerated skin tags(S). From September 2010 to December 2012, 197 consecutive patients were analysed according to both classifications. Considering pathological piles, I and II Goligher patients showed a complete agreement between pathological pile and grade, III Goligher patients had 80.5 % of pathological piles of III grade while IV Goligher patients had only 44.3 % of IV grade pathological piles (p < 0.001). Regarding the distribution of the other anatomical variables: F, E, S described in SPHC, the results showed that F was present in 18.3 % while ES was present in 46.2 %. Goligher's Classification has showed to be an inadequate tool to overview surgical outcome or to compare surgical procedure, particularly for high grades, while SPHC showed to be a feasible instrument both to describe and to compare patients affected by hemorrhoid disease. PMID- 26547760 TI - Cardiac Troponin and its Relationship to Cardiovascular Outcomes in Community Populations - A Systematic Review and Meta-analysis. AB - BACKGROUND: The clinical relevance of minor elevations of cardiac troponin (cTn) in the general population remains uncertain. The objective of this systematic review was to examine the literature and evaluate the prevalence of raised cTn in asymptomatic, community populations and explore the strength of the relationship between cTn and cardiovascular mortality amongst those studied. METHODS: Studies were identified by searching Medline, Embase, CINAHL, EBM Reviews, Cochrane Library and using the "related citation" search tool in PubMed from inception through August 2014. Prospective cohort studies of asymptomatic individuals recruited from the community (age >= 18 years) that assessed the relationship between cTn levels and mortality or cardiovascular events were included. RESULTS: Twenty-one prospective studies involving 64,855 participants were identified. An elevated cTn measurement (>99th percentile) occurred in 5% of individuals and was associated with a tripling of risk of mortality (adjusted RR 3.07, 95% confidence interval [CI] 2.32-4.06) and cardiovascular mortality (adjusted RR 3.30, 95% CI 1.77-6.12). In studies including high sensitivity assays, cTn was detectable in 58% of individuals. A detectable cardiac troponin T (cTnT) was also associated with an increased risk of cardiovascular mortality (adjusted RR 1.32, 95% CI 1.10 - 1.59). The risk increased with increasing cTnT level. CONCLUSIONS: Elevated troponin in asymptomatic individuals in the community is associated with a tripling of risk of all-cause and cardiovascular mortality. Cardiac troponin T (cTnT) is generally not measured in this group of patients, but may potentially have utility in predicting risk in this population. Further research is required to assess if this risk is modifiable with usual primary prevention treatments. PMID- 26547761 TI - Contact allergy in cheilitis. AB - BACKGROUND: Recalcitrant non-actinic cheilitis may indicate contact allergy. OBJECTIVES: This study aimed to determine the prevalence of allergic contact cheilitis (ACC) in patients with non-actinic cheilitis and to identify the most relevant allergens. METHODS: We used an institutional database to identify patients with non-actinic cheilitis who underwent patch testing between January 1, 2001, and August 31, 2011, and conducted a retrospective review of patch test results in these patients. Additional data were obtained from institutional electronic medical records. RESULTS: Ninety-one patients (70 [77%] female; mean age: 51 years) were included in the study. Almost half (41 [45%]) had a final diagnosis of ACC. Patch testing was performed in line with universally accepted methods, with application on day 1, allergen removal and an initial reading on day 3, and the final reading on day 5. The allergens of most significance were fragrance mix, Myroxylon pereirae resin, dodecyl gallate, octyl gallate, and benzoic acid. Nickel was the most relevant metal allergen. CONCLUSIONS: Contact allergy is an important consideration in recalcitrant cheilitis. Fragrances, antioxidants, and preservatives dominated the list of relevant allergens in our patients. Nickel and gold were among the top 10 allergens. Almost half (45%) of these patients had a final diagnosis of ACC. Patch testing beyond the oral complete series should be undertaken in any investigation of non-actinic cheilitis. PMID- 26547762 TI - Fiber Typing of the Erector Spinae and Multifidus Muscles in Healthy Controls and Back Pain Patients: A Systematic Literature Review. AB - OBJECTIVE: Understanding the changes in muscle fiber typing is relevant in the context of muscle disorders because it provides information on the metabolic profile and functional capacity. The aim of this study was to systematically review the literature comparing muscle fiber typing in the back muscles of healthy subjects with low back pain (LBP) patients. METHODS: Predefined keywords regarding muscle fiber typing and back muscles were combined in PubMed and Web of Science electronic search engines from inception to August 2014. Full-text articles were independently screened by 2 independent, blinded researchers. Full texts fulfilling the predefined inclusion criteria were assessed on risk of bias by 2 independent researchers, and relative data were extracted. Data were not pooled because of heterogeneity in biopsy locations and population. RESULTS: From the 214 articles that were identified, 18 met the inclusion criteria. These articles evaluated the muscle fiber type distribution or proportional fiber type area between muscles, muscle layers, men, and women or healthy subjects and LBP patients. Regarding muscle fiber type distribution, findings in healthy subjects and LBP patients show no or inconclusive evidence for intermuscular and interindividual differentiation. Studies evaluating the proportional fiber type area also suggest little intermuscular differentiation but provide plausible evidence that the proportional area occupied by type I fibers is higher in women compared to men. The evidence for differentiation based on the presence of low back pain is conflicting. CONCLUSION: This study found that the evidence regarding muscle fiber typing in back muscles is either inconclusive or shows little differences. The most plausible evidence exists for differentiation in proportional fiber type area depending on sex. PMID- 26547765 TI - Past WFITN Meetings. PMID- 26547766 TI - Letter from the President of WFITN. PMID- 26547767 TI - Welcome Message. PMID- 26547763 TI - Comparing Propensity Score Methods for Creating Comparable Cohorts of Chiropractic Users and Nonusers in Older, Multiply Comorbid Medicare Patients With Chronic Low Back Pain. AB - OBJECTIVE: Patients who use complementary and integrative health services like chiropractic manipulative treatment (CMT) often have different characteristics than do patients who do not, and these differences can confound attempts to compare outcomes across treatment groups, particularly in observational studies when selection bias may occur. The purposes of this study were to provide an overview on how propensity scoring methods can be used to address selection bias by balancing treatment groups on key variables and to use Medicare data to compare different methods for doing so. METHODS: We described 2 propensity score methods (matching and weighting). Then we used Medicare data from 2006 to 2012 on older, multiply comorbid patients who had a chronic low back pain episode to demonstrate the impact of applying methods on the balance of demographics of patients between 2 treatment groups (those who received only CMT and those who received no CMT during their episodes). RESULTS: Before application of propensity score methods, patients who used only CMT had different characteristics from those who did not. Propensity score matching diminished observed differences across the treatment groups at the expense of reduced sample size. However, propensity score weighting achieved balance in patient characteristics between the groups and allowed us to keep the entire sample. CONCLUSIONS: Although propensity score matching and weighting have similar effects in terms of balancing covariates, weighting has the advantage of maintaining sample size, preserving external validity, and generalizing more naturally to comparisons of 3 or more treatment groups. Researchers should carefully consider which propensity score method to use, as using different methods can generate different results. PMID- 26547768 TI - ICS2015 - Welcome Message. PMID- 26547769 TI - WFITN Executive Committees. PMID- 26547770 TI - WFITN Faculty List. PMID- 26547771 TI - Thank you to our Sponsors - WFITN. PMID- 26547772 TI - Thank you to our Sponsors - ICS. PMID- 26547773 TI - WFITN Congress Information. PMID- 26547774 TI - WFITN Symposia. PMID- 26547775 TI - Venue Map. PMID- 26547776 TI - Exhibition Hall. PMID- 26547777 TI - At a Glance. PMID- 26547778 TI - Program WFITN , Monday 9 November 2015. PMID- 26547780 TI - Program WFITN, Wednesday 11 November 2015. PMID- 26547779 TI - Program WFITN, Tuesday 10 November 2015. PMID- 26547781 TI - Program WFITN, Thursday 12 November 2015. PMID- 26547782 TI - Joint Program WFITN and ICS, Friday 13 November 2015. PMID- 26547783 TI - ICS2015 Program. PMID- 26547784 TI - WFITN 2015 Abstracts: Oral Expositions. PMID- 26547785 TI - WFITN 2015 Abstracts: Poster Display. PMID- 26547788 TI - Serum vitamin D and functional impairment in octogenarian women. AB - PURPOSE: Serum vitamin D deficiency has been associated with frailty in people aged 65 and over, however its relationship with functional impairment has not been investigated in octogenerian (aged 80-90 years) institutionalized women. METHODS: We assessed functional impairment in this latter group by measuring frailty syndrome and other geriatric and psychological assessment scales: the Tinetti gait and balance index to determine the risk for falls, the Barthel index to measure the basic activities of daily living, the Lawton index for instrumental activities, the mini-mental score examination test for cognitive impairment, the Yesavage scale for geriatric depression, and the Norton scale for the risk of ulceration. RESULTS: Frail individuals had significantly reduced serum vitamin D concentrations (measured as total 25-hydroxyvitamin D; 25(OH)D) compared to robust individuals, but reduced 25(OH)D concentration did not significantly correlate with frailty syndrome severity, and mean 25(OH)D concentrations were within the recommended levels in all groups. The 25(OH)D concentration did not correlate with any of the blood analytical parameters measured and with the geriatric assessment scales used, suggesting a selective relationship with frailty. CONCLUSION: These results highlight the need to individualize treatment such as vitamin D supplementation in order to treat frailty syndrome. PMID- 26547789 TI - Anti-angiogenic and anti-inflammatory effect of Magnolol in the oxygen-induced retinopathy model. AB - OBJECTIVE: In the present study, we investigated the effects of Magnolol on the retinal neovascularization (RNV) and local glial cells in an oxygen-induced retinopathy (OIR) model and explored their molecular mechanisms. MATERIALS AND METHODS: Neonatal C57BL/6J mice were subjected to 75% O2 +/- 5% from postnatal day (P) 7 to P12 and subsequently returned to room air. Mice were injected with 25 mg/kg Magnolol intraperitoneally once a day from P12 to P17, then retinas were harvested and flat-mounted to assess the retinal vessels, astrocytes and microglia. To clarify the molecular mechanisms of Magnolol, we observed the level of inflammatory cytokines such as interleukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and analyzed the hypoxia inducible factor (HIF)-1alpha/vascular endothelial growth factor (VEGF) pathway in OIR mice. RESULTS: Intraperitoneal administration of Magnolol resulted in significant reduction of RNV without retinal toxicity or perturbation of developmental retinal angiogenesis. In addition, Magnolol preserved the astrocyte morphology and diminished the activation of microglia. Moreover, Magnolol down regulated the expression of inflammatory cytokines and inactivated the HIF 1alpha/VEGF pathway. CONCLUSIONS: These results indicated that Magnolol might have potential for the treatment of pathological retinal angiogenesis and glial dysfunctions via anti-inflammation and inhibition of HIF-1alpha/VEGF pathway. PMID- 26547790 TI - Hyperbaric index in the primary prevention of hypertensive complications in high risk pregnancy. AB - INTRODUCTION: Preeclampsia (PE) is a major cause of fetal morbidity and mortality. In the Western World, PE affects 2-7% of pregnancies and is responsible for 50,000 deaths annually. Early detection is a priority as it can change the clinical course, but there are no biomarkers or instrumental methods with high sensitivity and specificity. Only the hyperbaric index has a sensitivity and specificity of 99% for early identification of pregnant women at risk of developing PE, but its use is not widespread. OBJECTIVE: To assess the usefulness of the hyperbaric index in the primary prevention of hypertensive pregnancy complications in a public healthcare area. MATERIAL AND METHODS: This is a retrospective study of pregnancies that occurred in our area during the period 2007-2012 (N=11,784). The diagnosis was established by the hyperbaric index and pregnant women at risk were treated with ASA at night. RESULTS: In pregnant patients referred to the nephrology clinic (38.2%), diagnosed as high risk for PE, and treated with 100mg ASA/night (from week 17), the incidence of PE episodes was reduced by 96.94. PMID- 26547791 TI - Functional variants inPXRare associated with colorectal cancer susceptibility in Chinese populations. AB - BACKGROUND: As an important member of the steroid nuclear receptor family, recent research has suggested that PXR may play important roles in the development of multiple cancers. However, no well-designed studies has been conducted to investigate the associations between genetic polymorphisms of PXR and colorectal cancer (CRC) risk in Chinese populations. MATERIALS AND METHODS: We performed a hospital-based case-control analysis to assess two genetic polymorphisms in the 3'-untranslated regions (3'-UTR) via allele-specific MALDI-TOF mass spectrometry assay and evaluated the associations between two polymorphisms and risk of CRC. RESULTS: The PXR rs3814058C>T polymorphism was significantly associated with a higher risk of CRC (P<10-3), and the CT/TT variant genotypes had an increased CRC risk (adjusted odds ratio=1.54, 95% confidence interval=1.27-1.83) comparing CC genotype. In stratified analyses, rs3814058CT+TT genotypes was associated with increased risk among alcohol consumers (P=0.002). In vitro experiments indicated that the rs3814058C to rs3814058T transition gained a new binding of the microRNA hsa-miR-129-5p and decreased the PXR expression. CONCLUSIONS: Our data suggest that the functional polymorphism rs3814058C>T in 3'-UTR of PXR may be a functional biomarker to predict risk of CRC. PMID- 26547792 TI - Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population. AB - Controversial data have emerged on the association between cancer risk and the single-nucleotide polymorphism (SNP, rs920778C>T) in Hox transcript antisense RNA (HOTAIR). No data on the association between HOTAIR polymorphism and breast cancer (BC) susceptibility and reproductive factors have been reported in China. In this study we investigated the association between HOTAIR polymorphisms and BC susceptibility in a population-based case-control study of 502 cases and 504 matched controls in China. Three haplotype tagging SNPs (rs1899663, rs4759314, rs920778) of HOTAIR were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created-restriction-site PCR (CRS RFLP) assays. False-positive report probability (FPRP) was calculated to test for false-positive associations. Interactions between the SNPs and reproductive factors were further evaluated by the multifactor dimensionality reduction (MDR) method. BC risk reduction was confined to subgroups of age at menarche >14 (OR: 0.42, 95%CI: 0.21, 0.82) and number of pregnancies >2 (OR: 0.65, 95%CI: 0.49, 0.95) for GT+TT rs1899663, and age at menopause <= 50 (OR: 0.97, 95%CI: 0.84, 0.99) for AG+GG rs4759314. Subjects with Trs920778 had a significantly increased risk of breast cancer (OR: 1.41, 95%CI: 1.13, 1.75). We observed a significant interaction between rs920778 and reproductive factors, including age at menopause, number of abortions, and family history. Our results were unlikely to be false positives according to FPRP calculation. In conclusion, genetic variant rs920778 in HOTAIR significantly increased the risk of BC, and it may have apparent interaction with reproductive factors in the progression on BC. These findings extend available data on the association between HOTAIR polymorphisms and BC susceptibility. PMID- 26547793 TI - Validation of sun exposure and protection index (SEPI) for estimation of sun habits. AB - BACKGROUND: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individual's sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). METHOD: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. RESULTS: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearman's Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbach's alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. CONCLUSIONS: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection. PMID- 26547794 TI - The plant microbiome explored: implications for experimental botany. AB - The importance of microbial root inhabitants for plant growth and health was recognized as early as 100 years ago. Recent insights reveal a close symbiotic relationship between plants and their associated microorganisms, and high structural and functional diversity within plant microbiomes. Plants provide microbial communities with specific habitats, which can be broadly categorized as the rhizosphere, phyllosphere, and endosphere. Plant-associated microbes interact with their host in essential functional contexts. They can stimulate germination and growth, help plants fend off disease, promote stress resistance, and influence plant fitness. Therefore, plants have to be considered as metaorganisms within which the associated microbes usually outnumber the cells belonging to the plant host. The structure of the plant microbiome is determined by biotic and abiotic factors but follows ecological rules. Metaorganisms are co-evolved species assemblages. The metabolism and morphology of plants and their microbiota are intensively connected with each other, and the interplay of both maintains the functioning and fitness of the holobiont. Our study of the current literature shows that analysis of plant microbiome data has brought about a paradigm shift in our understanding of the diverse structure and functioning of the plant microbiome with respect to the following: (i) the high interplay of bacteria, archaea, fungi, and protists; (ii) the high specificity even at cultivar level; (iii) the vertical transmission of core microbiomes; (iv) the extraordinary function of endophytes; and (v) several unexpected functions and metabolic interactions. The plant microbiome should be recognized as an additional factor in experimental botany and breeding strategies. PMID- 26547796 TI - Myopia and/or longer axial length are protective against diabetic retinopathy: a meta-analysis. AB - PURPOSE: To evaluate the current evidence of the relationship between myopia, together with its structural and refractive component, and diabetic retinopathy (DR) risk. METHODS: A systematic search was performed up to April, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Three models were used to assess the association between myopia and risk of DR: axial length (AL) (per millimetre increase) and DR; myopia (myopia versus non-myopia) and DR; refractive error (RE) (per D decrease) and DR. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test. RESULTS: A total of 11 studies that met the predefined criteria were included in this meta-analysis. Overall, longer AL (per millimetre increase) was associa-ted with a significantly decreased risk of DR (combined OR, 0.75; 95% CI, 0.65-0.86; p < 0.001); myopic eyes (myopia versus non-myopia) showed a lower risk of DR (combined OR, 0.70; 95% CI, 0.58-0.85; p < 0.001). A greater degree of myopic RE (per D decrease) also revealed a significantly decreased risk of DR (combined OR, 0.89; 95% CI, 0.85-0.93; p < 0.001). The sensitivity analyses and cumulative meta-analysis showed similar results. No publication bias was detected in any of the three models. CONCLUSIONS: This meta-analysis suggests that both myopic refraction and longer AL are associated with a lower risk of DR. Further studies are needed to determine exact mechanisms underpinning the protective effect of myopia against DR. PMID- 26547795 TI - JAZ7 negatively regulates dark-induced leaf senescence in Arabidopsis. AB - JASMONATE ZIM-domain (JAZ) proteins play important roles in plant defence and growth by regulating jasmonate signalling. Through data mining, we discovered that the JAZ7 gene was up-regulated in darkness. In the dark, the jaz7 mutant displayed more severe leaf yellowing, quicker chlorophyll degradation, and higher hydrogen peroxide accumulation compared with wild-type (WT) plants. The mutant phenotype of dark-induced leaf senescence could be rescued in the JAZ7 complemented and -overexpression lines. Moreover, the double mutants of jaz7 myc2 and jaz7 coi1 exhibited delayed leaf senescence. We further employed GeneChip analysis to study the molecular mechanism. Some key genes down-regulated in the triple mutant myc2 myc3 myc4 were up-regulated in the jaz7 mutant under darkness. The Gene Ontology terms 'leaf senescence' and 'cell death' were significantly enriched in the differentially expressed genes. Combining the genetic and transcriptomic analyses together, we proposed a model whereby darkness can induce JAZ7, which might further block MYC2 to suppress dark-induced leaf senescence. In darkness, the mutation of JAZ7 might partially liberate MYC2/MYC3/MYC4 from suppression, leading the MYC proteins to bind to the G-box/G-box-like motifs in the promoters, resulting in the up-regulation of the downstream genes related to indole-glucosinolate biosynthesis, sulphate metabolism, callose deposition, and JA-mediated signalling pathways. In summary, our genetic and transcriptomic studies established the JAZ7 protein as an important regulator in dark-induced leaf senescence. PMID- 26547797 TI - Intraoperative Technique for Evaluation of the Interosseous Ligament of the Forearm. AB - PURPOSE: To introduce a technique for the diagnosis of interosseous ligament (IOL) disruption based on lateral displacement of the radius after radial head resection and to determine the cutoff value of the lateral displacement for the diagnosis of disruption, the best elbow position for testing, and the diagnostic performance of the technique in different positions. METHODS: We used 10 fresh frozen cadavers. After resection of the radial head, a Steinman pin was placed into the radius medullary canal and used to mark the pin location on the capitellum. We applied 1 kg force to pull the proximal radius laterally and measured the displacement in full supination, neutral, and full pronation of the forearm with the elbow in extension and then in 90 degrees flexion. All measurements were performed once with the IOL intact and again with it cut. To assess diagnostic efficacy, receiver operating characteristics curves were constructed. To determine the quality of the technique, we measured the area under the receiver operating characteristics curve for each position. We also determined the cutoff value to obtain the highest sensitivity and specificity. RESULTS: The area under the curve of the test in extension-supination and flexion supination showed that these positions were excellent for the diagnosis of IOL disruption. The cutoff value of 5.5 mm lateral displacement in extension supination had 100% sensitivity and 90% specificity. In flexion-supination, the cutoff value of 9 mm had 100% sensitivity and 90% specificity for the diagnosis of IOL disruption. CONCLUSIONS: This maneuver was reliable and accurate in cadavers with complete IOL disruption. It is likely that in an intraoperative setting, these results will be reproducible. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II. PMID- 26547798 TI - The HPA axis in bipolar disorder: Systematic review and meta-analysis. AB - OBJECTIVES: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). METHODS: Meta-analysis and meta regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. RESULTS: Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants' age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. CONCLUSIONS: BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD. PMID- 26547799 TI - A Non-Reciprocal Autosomal Translocation 64,XX, t(4;10)(q21;p15) in an Arabian Mare with Repeated Early Embryonic Loss. AB - Balanced autosomal translocations are a known cause for repeated early embryonic loss (REEL) in horses. In most cases, carriers of such translocations are phenotypically normal, but the chromosomal aberration negatively affects gametogenesis giving rise to both genetically balanced and unbalanced gametes. The latter, if involved in fertilization, result in REEL, whereas gametes with the balanced form of translocation will pass the defect into next generation. Therefore, in order to reduce the incidence of REEL, identification of translocation carriers is critical. Here, we report about a phenotypically normal 3-year-old Arabian mare that had repeated resorption of conceptuses prior to day 45 of gestation and was diagnosed with REEL. Conventional and molecular cytogenetic analyses revealed that the mare had normal chromosome number 64,XX but carried a non-mosaic and non-reciprocal autosomal translocation t(4;10)(q21;p15). This is a novel translocation described in horses with REEL and the first such report in Arabians. Previous cases of REEL due to autosomal translocations have exclusively involved Thoroughbreds. The findings underscore the importance of routine cytogenetic screening of breeding animals. PMID- 26547800 TI - Altered expression of keratin 14 in lesional epidermis of autoimmune skin diseases. AB - BACKGROUND: Keratin 14 (K14) is an intermediate filament protein that is mainly expressed in the basal layer of healthy stratified epithelia. K14 has been identified as an autoantigen in the autoimmune-mediated skin disease of Scurfy mice and patients with the "immune dysregulation polyendocrinopathy, enteropathy, and X-linked" syndrome. OBJECTIVES: To examine whether K14 is a target protein in autoimmune skin diseases (ASD), we analyzed the expression pattern of K14 in lesional skin of patients with lichen ruber, cutaneous lupus erythematosus, dermatomyositis, graft-versus-host disease, psoriasis, and pemphigus vulgaris, and evaluated the reactivity of patient sera with recombinantly expressed and epidermis-derived K14. METHODS: K14 expression was analyzed by immunohistochemistry on paraffin-embedded tissue sections of 17 healthy individuals and 58 patients with ASD. Sera from 10 healthy individuals and 41 patients with ASD were analyzed by Western blot for the presence of anti-K14 autoantibodies. RESULTS: In skin of patients with ASD, K14 expression is retained in suprabasal layers. In ASD with interface dermatitis, we observed focal loss of K14 within the basal layer and in hair follicles as well. A scattered dot-like K14 staining is seen in papillary dermis, most prominently in cutaneous lupus erythematosus and lichen ruber. Using Western blot, we show that sera of different patients with ASD recognize recombinantly expressed K14. CONCLUSION: We show focal loss of K14 in the basal epidermis correlating with interface dermatitis and hair follicle involvement. Moreover, enhanced reactivity of sera of patients with atopic dermatitis with K14 suggests K14 may function as an autoantigen in ASD. PMID- 26547801 TI - Prognostic impact of pattern-based grading system by the new IASLC/ATS/ERS classification in Asian patients with stage I lung adenocarcinoma. AB - OBJECTIVES: We examined the prognostic effect of the grading system based on the new IASLC/ATS/ERS classification in an Asian cohort of patients with early-stage lung adenocarcinoma. MATERIALS AND METHODS: Patients with a lung adenocarcinoma less than 3cm in diameter that had undergone complete anatomic resection, diagnosed with pT1a-2aN0M0 consecutively from 2004 to 2013, were enrolled. All specimens were reviewed according to the new IASLC/ATS/ERS classification. The growth patterns were divided into three major categories: grade 1 for lepidic growth, grade 2 for acinar and papillary patterns, and grade 3 for solid and micropapillary patterns. Each tumor was then graded according to the modified grading system, the final score being the sum of the two most predominant grades. The correlations of clinical and pathological factors with disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: In total, 201 adenocarcinomas were eligible for score grading. Only 37 (18.4%) patients had a pure pathological growth pattern. Higher stage, greater tumor diameter, positive lymphovascular invasion, and a higher score were associated with shorter DFS. In contrast, stage no longer had a significant impact on OS in a multivariable analysis. Acinar/papillary-predominant tumors with a score of 3 or 4 were associated with better survival than those with a score of 5 (5-year DFS rate: 64.68 vs. 44.18%, HR=2.19, 95% CI: 1.24-3.87; 5-year OS rate: 85.61 vs. 68.59%, HR=3.03, 95% CI: 1.25-7.32). CONCLUSION: The architectural scores may help to stratify survival differences among certain predominant growth subtypes of adenocarcinoma. PMID- 26547802 TI - MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor. AB - BACKGROUND: MET splice site mutations resulting in an exon 14 deletion have been reported to be present in about 3% of all lung adenocarcinomas. Patients with lung adenocarcinoma and a MET splice site mutation who have responded to MET inhibitors have been reported. The CRISPR/Cas9 system is a recently developed genome-engineering tool that can easily and rapidly cause small insertions or deletions. MATERIALS AND METHODS: We created an in vitro model for MET exon 14 deletion using the CRISPR/Cas9 system and the HEK293 cell line. The phenotype, which included MET inhibitor sensitivity, was then investigated in vitro. Additionally, MET splice site mutations were analyzed in several cancers included in The Cancer Genome Atlas (TCGA) dataset. RESULTS: An HEK293 cell line with a MET exon 14 deletion was easily and rapidly created; this cell line had a higher MET protein expression level, enhanced MET phosphorylation, and prolonged MET activation. In addition, a direct comparison of phenotypes using this system demonstrated enhanced cellular growth, colony formation, and MET inhibitor sensitivity. In the TCGA dataset, lung adenocarcinomas had the highest incidence of MET exon 14 deletions, while other cancers rarely carried such mutations. Approximately 10% of the lung adenocarcinoma samples without any of driver gene alterations carried the MET exon 14 deletion. CONCLUSIONS: These findings suggested that this system may be useful for experiments requiring the creation of specific mutations, and the present experimental findings encourage the development of MET-targeted therapy against lung cancer carrying the MET exon 14 deletion. PMID- 26547803 TI - ALK-FISH borderline cases in non-small cell lung cancer: Implications for diagnostics and clinical decision making. AB - BACKGROUND: Fluorescence in-situ hybridization (FISH) for the detection of ALK rearrangements in non-small cell lung cancer (NSCLC) is based on at first sight clear cut-off criteria (>=15% of tumor cells) for split signals (SS) and single red signals (SRS). However, NSCLC with SS-counts around the cut-off may cause interpretation problems. MATERIAL AND METHODS: Tissue microarrays containing 753 surgically resected NSCLCs were independently tested for ALK-alterations by FISH and immunohistochemistry (IHC). Our analysis focused on samples with SS/SRS in the range between 10% and 20% (ALK-FISH borderline group). To better understand the role of these samples in routine diagnostics, we performed statistical analyses to systematically estimate the probability of ALK-FISH-misclassification (false negative or positive) for different numbers of evaluated tumor cell nuclei (30, 50, 100, and 200). RESULTS: 94.3% (710/753) of the cases were classified as unequivocally (<10% or >=20%) ALK-FISH-negative (93%; 700/753) or positive (1.3%; 10/753) and showed concordant IHC results. 5.7% (43/753) of the samples showed SS/SRS between 10% and 20% of the tumor cells. Out of these, 7% (3/43; ALK-FISH: 14%, 18% and 20%) were positive by ALK-IHC, while 93% (40/43) had no detectable expression of the ALK-protein. Statistical analysis showed that ALK-FISH misclassifications occur frequently for samples with rearrangements between 10% and 20% if ALK-characterization is based on a sharp cut-off point (15%). If results in this interval are defined as equivocal (borderline), statistical sampling-related ALK-FISH misclassifications will occur in less than 1% of the cases if 100 tumor cells are evaluated. CONCLUSION: While ALK status can be determined robustly for the majority of NSCLC by FISH our analysis showed that ~6% of the cases belong to a borderline group for which ALK-FISH evaluation has only limited reliability due to statistical sampling effects. These cases should be considered equivocal and therapy decisions should include additional tests and clinical considerations. PMID- 26547804 TI - Impact of a Four-Point Order-Priority Score on Imaging Examination Performance Times. AB - BACKGROUND: Many hospitals use a traditional categoric system (eg, STAT, ASAP [as soon as possible], routine) to prioritize orders for imaging examination performance. If left undefined, these categories contain ambiguity, which contributes to errant or misused categorizations, and ultimately, lost opportunity to optimally direct resources toward timely patient care. Our hospital implemented ordinal order-priority categories with specific definitions. We sought to determine the impact of this prioritization method on examination performance time and consistency. METHODS: A four-level numeric priority system with clinical definitions for each category was implemented in 2011 to replace a traditional model for hospital imaging orders. Retrospective analysis was performed on imaging orders for three years (2011-2013) after implementation, to assess the order-to-performance time (OTPT), defined as the time between order placement by the provider and examination completion by the technologist. Consistency was measured by the length of the interquartile range for the OTPT distribution. Comparison was made to orders from the preimplementation year (2010), as a control. RESULTS: The OTPT and OTPT consistency for performed examinations were both predictably stratified by order-priority level. Relative to control, we observed a reduction in the percentage of prioritized examinations, as well as modest general improvements in OTPT and OTPT consistency. CONCLUSIONS: A revised order-priority system with ordinal categorizations and clinical definitions accompanying each priority level at order entry yielded desirable prioritization of imaging examination performance by technologists, as evidenced by appropriate stratification of turnaround times and consistency by level of priority. PMID- 26547805 TI - Syncope caused by right ventricular obstruction by pectus excavatum. PMID- 26547806 TI - Temporal variation of Bistorta vivipara-associated ectomycorrhizal fungal communities in the High Arctic. AB - Ectomycorrhizal (ECM) fungi are important for efficient nutrient uptake of several widespread arctic plant species. Knowledge of temporal variation of ECM fungi, and the relationship of these patterns to environmental variables, is essential to understand energy and nutrient cycling in Arctic ecosystems. We sampled roots of Bistorta vivipara ten times over two years; three times during the growing-season (June, July and September) and twice during winter (November and April) of both years. We found 668 ECM OTUs belonging to 25 different ECM lineages, whereof 157 OTUs persisted throughout all sampling time-points. Overall, ECM fungal richness peaked in winter and species belonging to Cortinarius, Serendipita and Sebacina were more frequent in winter than during summer. Structure of ECM fungal communities was primarily affected by spatial factors. However, after accounting for spatial effects, significant seasonal variation was evident revealing correspondence with seasonal changes in environmental conditions. We demonstrate that arctic ECM richness and community structure differ between summer (growing-season) and winter, possibly due to reduced activity of the core community, and addition of fungi adapted for winter conditions forming a winter-active fungal community. Significant month * year interactions were observed both for fungal richness and community composition, indicating unpredictable between-year variation. Our study indicates that addressing seasonal changes requires replication over several years. PMID- 26547807 TI - The prognostic significance of troponin I elevation in acute ischemic stroke. AB - BACKGROUND: The significance of cardiac troponin I (TnI) levels in patients with acute ischemic stroke remains unclear. METHODS: Data were prospectively collected on 1718 patients with acute ischemic stroke (2009-2010). Patients with positive TnI (peak TnI >=0.1 MUg/L) were assigned to the myocardial infarction (MI) group if they met diagnostic criteria. The remaining patients with positive TnI were assigned to the no-MI group. Patients were followed up for 1.4 +/- 1.1 years. Primary outcome was inhospital and long-term all-cause mortality. RESULTS: Positive TnI was present in 309 patients (18%), 119 of whom (39%) were classified as having MI. Positive TnI was independently associated with older age, hypertension, smoking, peripheral arterial disease, heart failure, higher systolic blood pressure, higher serum creatinine, and lower heart rate (P < .01). Patients with MI had the highest inpatient mortality (P < .001) and the lowest survival rate by Kaplan-Meier analysis (P < .0001). Peak TnI greater than or equal to 0.5 MUg/L, particularly if satisfying criteria for MI, was independently associated with long-term mortality (P < .0001); peak TnI less than 0.5 MUg/L alone was not when adjusted for covariates. CONCLUSION: Positive TnI greater than or equal to 0.5 MUg/L in patients with acute ischemic stroke was independently associated with worse outcomes. Patients with diagnosis of MI represent a particularly high-risk subgroup. PMID- 26547808 TI - Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy. PMID- 26547809 TI - Coordinated regulation of nitrogen supply mode and initial cell density for energy storage compounds production with economized nitrogen utilization in a marine microalga Isochrysis zhangjiangensis. AB - Lipids and carbohydrates are main energy storage compounds (ESC) of microalgae under stressed conditions and they are potential feedstock for biofuel production. Yet, the sustainable and commercially successful production of ESC in microalgae needs to consider nitrogen utilization efficiency. Here the impact of different initial cell densities (ICDs) on ESC accumulation in Isochrysis zhangjiangensis under two nitrogen supply modes (an initially equal concentration of nitrogen per-cell in the medium (N1) and an equal total concentration of nitrogen in the culture system (N2)) were investigated. The results demonstrated that the highest ESC yield (1.36gL(-1)) at N1, which included a maximal nitrogen supply in the cultivation system, and the highest ESC content (66.5%) and ESC productivity per mass of nitrogen (3.28gg(-1) (N) day(-1)) at N2, were all obtained under a high ICD of 8.0*10(6)cellsmL(-1). Therefore I. zhangjiangensis qualifies for ESC-enriched biomass production with economized nitrogen utilization. PMID- 26547810 TI - Outdoor cultures of Chlorella pyrenoidosa in the effluent of anaerobically digested activated sludge: The effects of pH and free ammonia. AB - A freshwater algae Chlorella pyrenoidosa was cultured outdoors using anaerobically digested activated sludge effluent. The effects of pH variations were evaluated. The coupled pH variations and free ammonia toxicity significantly affected the algal growth, lipids accumulation and contamination control during every season. The free ammonia toxicity at high pH levels actually inhibited the algal growth. Compared to an optimal algal growth at a pH of 5.7-6.5, biomass productivity at a high pH of 8.3-8.8 was reduced by 67.15+/-6.98%, 54.39+/-6.42% and 83.63+/-5.71% in the spring, fall and summer, respectively. When the pH rose above 9.1-9.6, algae were unable to grow in the wastewater. However, high pH levels reduced contamination (e.g., bacteria and microalgae grazers) and triggered lipids accumulation in algal cells. These findings suggest that pH control strategies are essential for this type of algal wastewater system, where ammonia is the dominant nitrogen source. PMID- 26547811 TI - Semi-continuous methane production from undiluted brown algae using a halophilic marine microbial community. AB - Acclimated marine sediment-derived culture was used for semi-continuous methane production from materials equivalent to raw brown algae, without dilution of salinity and without nutrient supply, under 3 consecutive conditions of varying organic loading rates (OLRs) and hydraulic retention time (HRT). Methane production was stable at 2.0gVS/kg/day (39-day HRT); however, it became unstable at 2.9gVS/kg/day (28-day HRT) due to acetate and propionate accumulation. OLR subsequently decreased to 1.7gVS/kg/day (46-day HRT), stabilizing methane production beyond steady state. Methane yield was above 300mL/g VS at all OLRs. These results indicated that the acclimated marine sediment culture was able to produce methane semi-continuously from raw brown algae without dilution and nutrient supply under steady state. Microbial community analysis suggested that hydrogenotrophic methanogens predominated among archaea during unstable methane production, implying a partial shift of the methanogenic pathway from acetoclastic methanogenesis to acetate oxidation. PMID- 26547812 TI - Plant Life without Ethylene. AB - We propose that the ability to synthesize ethylene was selectively lost in evolution when the ancestors of fully aquatic higher plants lost their terrestrial lifestyle. We suggest that there has been negative selection on ethylene in these submerged species because it might interfere with growth in permanently deluged environments. PMID- 26547813 TI - A Novel Compound Analgesic Cream (Ketamine, Pentoxifylline, Clonidine, DMSO) for Complex Regional Pain Syndrome Patients. AB - BACKGROUND: Evidence suggests that complex regional pain syndrome (CRPS) is a manifestation of microvascular dysfunction. Topical combinations of alpha2 adrenergic receptor agonists or nitric oxide donors with phosphodiesterase or phosphatidic acid inhibitors formulated to treat microvascular dysfunction have been shown to reduce allodynia in a rat model of CRPS-I. Driven by these findings, we assessed the outcomes of CRPS patients treated with a compound analgesic cream (CAC) consisting of ketamine 10%, pentoxifylline 6%, clonidine 0.2%, and dimethyl sulfoxide 6% to 10%. METHODS: An audit was conducted on 13 CRPS patients who trialed the CAC. A detailed report was compiled for each patient which comprised baseline characteristics, including CRPS description, previous treatments, and pain scores (numerical pain rating scale; 0 to 10). Recorded outcomes consisted of pain scores, descriptive outcomes, and concurrent medications/treatments, for which basic analysis was performed to determine the effectiveness of the CAC. Case reports are presented for 3 patients with varying outcomes. RESULTS: Nine patients (69%) reported pain/symptom reduction (4.4 +/- 2.1 vs. 6.3 +/- 1.9) with use of the CAC. Six patients reported sustained benefits after 2 months of CAC use, and 2 patients reported complete resolution of pain/symptoms: one had early CRPS-I and the other received a partial CRPS diagnosis. An otherwise medication refractory and intolerant patient found partial benefit with the CAC. CONCLUSIONS: These results demonstrate promise for this topical combination as a useful treatment in multimodal therapy for patients with CRPS, with the potential to resolve pain/symptoms in early CRPS patients. PMID- 26547814 TI - Analysis of HFE mutations and non-HFE gene mutations (TFR2 and SLC40A1) in patients with phenotypic hemochromatosis from the Basque Country. PMID- 26547815 TI - Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates. AB - In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected. PMID- 26547816 TI - Insulin dependent diabetes mellitus (IDDM) and first trimester markers in prenatal screening for Down syndrome. PMID- 26547817 TI - The cryptoglandular theory revisited. PMID- 26547818 TI - Commentary on 'Impact of 3-dimensional endoanal ultrasound on the outcome of anal fistula surgery: a prospective cohort study'. PMID- 26547824 TI - The impact of infection with Schmallenberg virus on weaning rate in Irish sheep flocks. AB - Schmallenberg virus (SBV) disease emerged in Europe in 2011, with the virus initially identified in Germany, and the first confirmed case of SBV infection in Ireland diagnosed in a dairy calf in October 2012. SBV was subsequently confirmed by RT-PCR in 49 cattle herds and 39 sheep flocks. While these studies provide a good representation of the spatial distribution of SBV in Ireland, they do not quantify the impact of SBV on productivity. The objectives of this study were to assess the impact of SBV on weaning rate in Irish sheep flocks, based on data reported by Irish sheep farmers, and to evaluate weaning rate in sheep flocks as an indicator to be used in emerging disease surveillance systems. A questionnaire on productivity and management practices in sheep flocks was developed to gather data from sheep farmers. Valid responses from 267 sheep farmers were received. Negative binomial regression indicated that flocks with a confirmed SBV diagnosis had a weaning rate 0.9 times that of flocks free of SBV. The 10% reduction in weaning rates as a result of SBV is a justifiable concern for farmers and should be considered in formulating flock breeding policy. This study shows the value of a production database as an indicator of an emerging disease and the economic impact of that disease in Irish sheep flocks. PMID- 26547825 TI - Frailty Change and Major Osteoporotic Fracture in the Elderly: Data from the Global Longitudinal Study of Osteoporosis in Women 3-Year Hamilton Cohort. AB - Investigating the cumulative rate of deficits and the change of a frailty index (FI) chronologically is helpful in clinical and research settings in the elderly. However, limited evidence for the change of frailty before and after some nonfatal adverse health event such as a major osteoporotic fracture (MOF) is available. Data from the Global Longitudinal Study of Osteoporosis in Women 3 Year Hamilton cohort were used in this study. The changes of FI before and after onset of MOF were compared between the women with and without incident MOF. We also evaluated the relationship between risk of MOF, falls, and death and the change of FI and the absolute FI measures. There were 3985 women included in this study (mean age 69.4 years). The change of FI was significantly larger in the women with MOF than those without MOF at year 1 (0.085 versus 0.067, p = 0.036) and year 2 (0.080 versus 0.052, p = 0.042) post-baseline. The FI change was not significantly related with risk of MOF independently of age. However, the absolute FI measures were significantly associated with increased risk of MOF, falls, and death independently of age. In summary, the increase of the FI is significantly larger in the elderly women experiencing a MOF than their peer controls, indicating their worsening frailty and greater deficit accumulation after a MOF. Measures of the FI change may aid in the understanding of cumulative aging nature in the elderly and serve as an instrument for intervention planning and assessment. PMID- 26547826 TI - Interobserver variability in clinical target volume delineation for primary mediastinal B-cell lymphoma. AB - PURPOSE: The purpose of this study was to evaluate interobserver variability among radiation oncologists with experience in the field of lymphoma radiation therapy in the delineation of clinical target volume (CTV) in a challenging case of primary mediastinal B-cell lymphoma. METHODS AND MATERIALS: Ten experienced radiation oncologists were invited to a 1-day contouring session. The case of a 56-year-old man with primary mediastinal B-cell lymphoma with complete metabolic response after chemotherapy was chosen as the sample for the study. A brief presentation of his clinical history was given, together with guidelines for contouring. The 10 CTVs obtained were then compared in terms of variation in total volume and in craniocaudal, laterolateral, and anteroposterior diameters. The CTV with the best Dice similarity coefficient (DSC) between the union of all 10 CTVs and the individual CTV was considered the reference CTV, and the DSC and the Hausdorff distance (HD) for each volume compared with the reference CTV were then calculated. RESULTS: A significant variability was found in total volume (mean, 498.3 cm(3); range, 181.8-1003 cm(3)) and craniocaudal (median, 144.7 mm; range, 80.6-159 mm), laterolateral (median, 133.5 mm; range, 83.7-149.5 mm), and anteroposterior diameters (median, 136.2 mm; range, 84-150.5 mm). Analysis of the DSC and the HD showed a mean DSC of 0.53 (range, 0.31-0.74) and a mean HD of 6.4 cm (range, 1.8-14.8 cm). CONCLUSIONS: Results of this study strongly indicate the need to develop and share appropriate contouring guidelines among experts and suggest the promotion of specific educational activities to improve radiation therapy quality in both clinical trials and routine clinical practice. PMID- 26547827 TI - The American Board of Radiology Focused Practice Recognition in Brachytherapy (FPRB) Program: Opportunities lost, lessons learned, and future implications. AB - In 2011, the American Board of Medical Specialties approved a pilot project submitted by the American Board of Radiology for a Focused Practice Recognition in Brachytherapy initiative. Developers had anticipated significant interest within the profession and had hoped that the project would stimulate clinical interest, research, and education in the modality. A centerpiece of the project was a National Brachytherapy Registry, which was to serve as a dynamic longitudinal database for participants and the profession. Ultimately, the project did not achieve its anticipated goals and was terminated by the American Board of Radiology in 2015. Development, implementation, problems encountered, and potential implications and solutions are discussed. PMID- 26547828 TI - Image guidance and stabilization for stereotactic ablative body radiation therapy (SABR) treatment of primary kidney cancer. AB - PURPOSE: Stereotactic ablative body radiation therapy for primary kidney cancer treatment relies on motion management that can quantify both the trajectory of kidney motion and stabilize the patient. A prospective ethics-approved clinical trial of stereotactic treatment to primary kidney targets was conducted at our institution. Our aim was to report on specific kidney tumor motion and the inter- and intrafraction motion as seen on treatment. METHODS AND MATERIALS: Patients with tumor size <5 cm received a dose of 26 Gy in 1 fraction and those with tumor size >=5 cm received 42 Gy in 3 fractions. All patients underwent a 4-dimensional computed tomography planning scan, immobilized in a dual-vacuum system. A conventional linear accelerator cone beam computed tomography scan was used for pre-, mid-, and posttreatment imaging to verify target position. RESULTS: Between July 2012 and October 2014, 33 targets from 32 consecutive patients (24 males/8 females) were treated. Seventeen targets were prescribed 26 Gy/1 fraction and the remaining 16 targets received 42 Gy/3 fractions. Kidney motion at each of the poles was not affected by the presence of tumor (P = .875), nor was the motion statistically different from the corresponding contralateral kidney pole (P = .909). The mean 3-dimensional displacement of the target at mid- and posttreatment was 1.3 mm (standard deviation +/- 1.6) and 1.0 mm (standard deviation +/- 1.3), respectively. The maximum displacement in any direction for 95% of the fractions at mid- and posttreatment was <=3 mm. CONCLUSION: In summary, stereotactic ablative body radiation therapy of primary kidney targets can be accurately delivered on a conventional linear accelerator with protocol that has minimal intrafractional target motion. PMID- 26547829 TI - Ambulatory pulse oximetry as a clinical aid for the diagnosis and treatment response of radiation pneumonitis. AB - PURPOSE: Radiation pneumonitis (RP) is a clinical diagnosis, with no single best method of detection currently available. This study evaluated whether a decline between resting (rPO) and ambulatory (aPO) pulse oximetry (PO) levels after concurrent chemotherapy and radiation therapy (RT) can serve as a clinical aid in diagnosing and evaluating treatment response of grade 2-3 RP. METHODS AND MATERIALS: Between March 2007 and November 2013, rPO and aPO values were obtained from 55 patients immediately after definitive thoracic RT and at each subsequent visit, for up to 4 visits. Median values of the decline from rPO to aPO were compared between those with and without subsequent RP. A logistic regression model was used to determine an association between a drop in PO and, independently, clinically defined RP. RESULTS: RP was identified in 19 of 55 patients, with a median time to diagnosis of 56 days after RT. Twelve patients (22%) were diagnosed with grade 2 RP and 7 (13%) with grade 3 RP. According to a Wilcoxon rank sum test, the median calculated drop between rPO and aPO was greater in RP patients than in those without RP (median 4.21 and 1.01, respectively; P<.0001). After adjustment for total tumor dose and age, multivariate analyses revealed a 64.8% increase in the chance of RP development with every unit of decline in PO (P=.0014). After initiation of treatment with a corticosteroid, the mean difference in PO drop was compared with patients' baselines and demonstrated a statistically significant improvement, with peak PO value recovery after 2 weeks of corticosteroid therapy (P=.0001). CONCLUSIONS: Patients diagnosed with RP demonstrated an early, measurable drop between rPO and aPO that was detected at or before diagnosis. Consequent recovery in PO followed treatment with corticosteroids. PO measurements are cost-effective and readily available, and they can be a valuable tool to aid in diagnosing RP and gauging treatment response. PMID- 26547830 TI - Ten-year trends in safe radiation therapy delivery and results of a radiation therapy quality assurance intervention. AB - PURPOSE: This study reviews our institutional error data and assesses the effectiveness of a policy implemented January 1, 2011, as a "no rushed treatment" initiative to avoid universal, large-scale replanning for all patients in the event that a treatment unit is down for <=1 day. METHODS AND MATERIALS: Radiation error data between January 1, 2004, and December 31, 2014, were reviewed to determine absolute delivery error rates. Variables were compared (using a chi(2) or Fisher exact test) before and after the policy change, including planning versus delivery error status and differences in error type. We also evaluated time of day in relation to therapist shift change, deviation from scheduled time, and weekend treatment as predictors of error using a test of proportions or chi(2) test. RESULTS: Treatment delivery error rate over the entire period was 0.18% per fraction; the rate before intervention was 0.24% and after was 0.08%, P < .001. For the 5 years for which detailed records were available (2010-2014), 109 delivery errors were reported. Delivery error rate was 0.09%; before intervention 0.15% versus after, 0.08% (P = .005) and 94% were level 1 errors. Fifty-six percent were primary planning errors and 44% were primary delivery errors. Before intervention, large-scale replanning occurred 18 times/year versus 4.5/year after, with 21% versus 12% of errors directly attributable to large scale replanning. Fourteen error reports specifically implicated a rushed environment as causal. There was no significant difference in error rate based on time of day (P = .631). Error rates were higher for weekend simulation and treatments, 1.3% versus 0.09% per fraction (P < .001). CONCLUSIONS: Delivery error rates at our institution were similar compared with published series from other academic institutions. A significant improvement in delivery error rate was appreciated after implementation of a "no rushed treatment" initiative. A significantly higher error rate for weekend treatments was noted, warranting consideration of additional quality assurance measures. PMID- 26547832 TI - Impact of hospital length of stay on the distribution of Gram negative bacteria and likelihood of isolating a resistant organism in a Canadian burn center. AB - RATIONALE: The impact of hospital length of stay (LOS) on the distribution and susceptibility of Gram negative bacteria (GNB) causing infection in burn patients remains unexplored. Knowledge of causative pathogens is important in guiding empiric antibiotic therapy. OBJECTIVES: To characterize the distribution of GNB causing infection and to identify changes in susceptibility with LOS in a tertiary care burn center. METHODS: A retrospective review of all admissions to the Ross Tilley Burn Centre at Sunnybrook Health Sciences Centre with clinical cultures yielding GNB (duplicates excluded) between March 12, 2010 to July 17, 2013 was completed. Positive cultures were categorized into 5 clinically relevant time periods (in days) based on specimen collection date relative to the patient's date of admission: 0-7, 7-14, 14-21, 21-28, >28. Chi-square for proportions was used to compare the time periods. RESULTS: The proportion of patients with clinical cultures for P. aeruginosa increased with hospital LOS (0 7 days: 8% vs. >28 days: 55%; p<0.05). Conversely, clinical cultures for H. influenzae occurred primarily within the first 7 days of hospitalization (0-7 days: 36% vs. >28 days: 0.7%; p<0.05). Enterobacteriaceae isolation was highest between 7 and 14 days of hospitalization (7-14 days: 62% vs. >28 days: 38%; p<0.05). Antibiotic resistance was directly proportional to hospital LOS (% patients with multidrug resistant GNB increased from 6% [LOS 0-7 days] to 44% [LOS>28 days]; p<0.05). CONCLUSIONS: This study provides objective data documenting changes in species and resistance patterns of GNB causing infection in patients admitted to a burn center as a function of hospital LOS; which may support delaying the use of broad spectrum antibiotics (e.g. carbapenems and beta lactam/beta-lactamase inhibitors) in clinically stable patients. PMID- 26547831 TI - Shank-cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses. AB - The family of Shank scaffolding molecules (comprising Shank1, 2 and 3) are core components of the postsynaptic density (PSD) in neuronal synapses. Shanks link surface receptors to other scaffolding molecules within the PSD, as well as to the actin cytoskeleton. However, determining the function of Shank proteins in neurons has been complicated because the different Shank isoforms share a very high degree of sequence and domain homology. Therefore, to control Shank content while minimizing potential compensatory effects, a miRNA-based knockdown strategy was developed to reduce the expression of all synaptically targeted Shank isoforms simultaneously in rat hippocampal neurons. Using this approach, a strong (>75%) reduction in total Shank protein levels was achieved at individual dendritic spines, prompting an approximately 40% decrease in mushroom spine density. Furthermore, Shank knockdown reduced spine actin levels and increased sensitivity to the actin depolymerizing agent Latrunculin A. A SHANK2 mutant lacking the proline-rich cortactin-binding motif (SHANK2-DeltaPRO) was unable to rescue these defects. Furthermore, Shank knockdown reduced cortactin levels in spines and increased the mobility of spine cortactin as measured by single molecule tracking photoactivated localization microscopy, suggesting that Shank proteins recruit and stabilize cortactin at the synapse. Furthermore, it was found that Shank knockdown significantly reduced spontaneous remodelling of synapse morphology that could not be rescued by the SHANK2-DeltaPRO mutant. It was concluded that Shank proteins are key intermediates between the synapse and the spine interior that, via cortactin, permit the actin cytoskeleton to dynamically regulate synapse morphology and function. PMID- 26547833 TI - Beliefs about intimate partner violence: A survey of the Swedish general public. AB - Public interventions are considered to be an important means of preventing intimate partner violence (IPV). What people believe about the nature of IPV is likely to determine their propensity to intervene, but little is known at present about IPV beliefs among the general public. In a survey of 650 Swedish citizens, beliefs about the prevalence and causes of IPV, and viable means of intervention were assessed. Respondents estimated, on average, that IPV occurs in almost one quarter of all intimate relationships in Sweden, and that IPV is particularly prevalent in low-income groups, among non-European immigrants, in suburban areas, and in couples under the age of 50 years. Physical violence was believed to be the most frequent form of abuse in male offender-female victim cases, whereas psychological violence was considered most frequent in other combinations of offender and victim gender. Female respondents estimated a higher prevalence of IPV, attributed less blame to IPV victims, and suggested more means of intervention, than did male respondents. The findings are discussed in relation to empirical prevalence estimates, and implications are proposed. PMID- 26547834 TI - Racial and economic disparities in the treatment of penile squamous cell carcinoma: Results from the National Cancer Database. AB - PURPOSE: We evaluated sociodemographic and economic differences in overall survival (OS) of patients with penile SCC using the National Cancer Data Base (NCDB). METHODS: We identified 5,412 patients with a diagnosis of penile squamous cell carcinoma from 1998 to 2011 with clinically nonmetastatic disease and available pathologic tumor and nodal staging. OS was estimated using the Kaplan Meier method, and differences were determined using the log-rank test. Cox proportional hazard regression was performed to identify independent predictors of OS. RESULTS: Estimated median OS was 91.9 months (interquartile range: 25.8 not reached) at median follow-up of 44.7 months (interquartile range: 17.2-81.0). Survival did not change over the study period (P = 0.28). Black patients presented with a higher stage of disease (pT3/T4: 16.6 vs. 13.2%, P = 0.027) and had worse median OS (68.6 vs. 93.7 months, P<0.01). Patients with private insurance and median income>=$63,000 based on zip code presented with a lower stage of disease (pT3/T4: 11.6 vs. 14.7%, P = 0.002 and 12.0 vs. 14.0%, P = 0.042, respectively) and had better median OS (163.2 vs. 70.8 months, P<0.01 and 105.3 vs. 86.4 months, p = 0.001, respectively). On multivariate analysis, black race (hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 1.21-1.58; P<0.01) was independently associated with worse OS, whereas private insurance (HR = 0.79, 95% CI: 0.63-0.98; P = 0.028) and higher median income>=$63,000 (HR = 0.82; 95% CI: 0.72-0.93; P = 0.001) were independently associated with better OS. CONCLUSIONS: Racial and economic differences in the survival of patients with penile cancer exist. An understanding of these differences may help minimize disparities in cancer care. PMID- 26547835 TI - Evaluating the quality of internet information for breast cancer. AB - The internet is frequently used by patients for researching information regarding breast cancer. This study aims to assess the quality of these websites using validated tools. The term 'breast cancer' was searched for in 3 search engines. The top 20 results were selected, and duplicates and irrelevant websites were excluded. 26/34 websites were analysed using the DISCERN Plus tool, HONcode and the JAMA benchmarks. 46% of the websites were classed as 'excellent' when assessed with the DISCERN tool. The range of DISCERN scores was wide (range: 25 74). Nine websites were found to be HONcode certified. Seven websites complied with all four JAMA benchmarks. This study shows the quality of breast cancer information on the internet is on the whole good; however the range of quality is wide. We recommend healthcare professionals use all 3 tools together to establish which websites are best to advise which websites patients should trust. PMID- 26547836 TI - Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study. AB - PURPOSE: Our study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters. METHODS: Forty three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis. RESULTS: Median follow-up from the end of RT to the last check-up was 87 months (range 37-120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12. CONCLUSION: Our results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment. PMID- 26547837 TI - Symmetrization in jellyfish: reorganization to regain function, and not lost parts. AB - We recently reported a previously unidentified strategy of self-repair in the moon jellyfish Aurelia aurita. Rather than regenerating lost parts, juvenile Aurelia reorganize remaining parts to regain essential body symmetry. This process that we called symmetrization is rapid and frequent, and is not driven by cell proliferation or cell death. Instead, the swimming machinery generates mechanical forces that drive symmetrization. We found evidence for symmetrization across three other species of jellyfish (Chrysaora pacifica, Mastigias sp., and Cotylorhiza tuberculata). We propose reorganization to regain function without recovery of initial morphology as a potentially broad class of self-repair strategy beyond radially symmetrical animals, and discuss the implications of this finding on the evolution of self-repair strategies in animals. PMID- 26547838 TI - Editorial. PMID- 26547839 TI - Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients: a systematic review of randomised clinical trials with meta analysis and trial sequential analysis. AB - BACKGROUND: Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients. METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality, duration of mechanical ventilation, length of stay, and adverse events. Two reviewers independently assessed trials for inclusion, data extraction, and risk of bias. Risk ratios (RRs) with 95 % confidence intervals (CIs) were estimated by conventional cumulative meta-analysis, and the robustness of the primary estimate was assessed by TSA. RESULTS: Two trials (n = 63) were included; both were judged to have high risk of bias. There was no statistically significant difference in mortality (random effects model RR (95 % CI) 0.73 (0.09-5.77); P = 0.24; I (2) = 30 %). TSA could not be conducted because less than 1 % of the required information size had been accrued. None of the two trials reported adequate and detailed data on any of the secondary outcome measures. CONCLUSIONS: We found very low quantity and quality of evidence for use of nebulised dornase alfa in adult critically ill patients in this systematic review with meta-analysis. SYSTEMATIC REVIEW REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO), no. CRD442015016047. PMID- 26547840 TI - Non-alcoholic fatty liver disease among sasang constitutional types: a population based study in Korea. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is highly prevalent in populations with metabolic conditions such as obesity and type II diabetes. Specific types of Sasang constitution can act as a risk factor for metabolic diseases, but there are no studies addressing the association between the Sasang constitutional types (SCTs) and NAFLD. METHODS: A total of 1184 individuals (508 males, 676 females) that enrolled in the Korean Genome and Epidemiology Study were included in the present study. Classification of SCTs was done with an integrated diagnostic model. NAFLD was diagnosed when the liver attenuation index (LAI) value was <5 Hounsfield units using computed tomography. Relationships between the SCTs and NAFLD were analyzed using multiple logistic regressions. RESULTS: The average LAI was 13.3+/ 6.0 in the So-eum (SE) type, 12.3+/-7.0 in the So-yang (SY) type, and 6.5+/-9.9 in the Tae-eum (TE) type. Prevalence of NAFLD was 4.7% in the SE type, 14.0% in the SY type, and 34% in the TE type. Even after adjusting for possible confounders, the SY and TE types continued to show a 3.90-fold (95% CI, 1.60 9.51; P=0.0028) and 3.36-fold (95% CI, 1.42-7.92; P=0.0057) increase in chance of having NAFLD, respectively, compared with the SE type. In the additional analysis including only non-obese subjects, the odds ratio of NAFLD was 3.27 (95% CI, 1.29 8.29; P=0.0126) in the SY type and 3.53 (95% CI, 1.30-9.58; P=0.0134) in the TE type compared with SE type. In the multivariate analysis to determine which parameter had an independent association with NAFLD, higher body mass index, alanine aminotransferase (ALT), triglyceride (TG), and low high-density lipoprotein cholesterol were independently associated with developing NAFLD in the SY type. In contrast, male sex, alcohol consumption, higher ALT, TG, and fasting glucose were risk factors for NAFLD in the TE type. CONCLUSIONS: These results indicated that the SY and TE types are independent risk factors for NAFLD. PMID- 26547842 TI - A new method to assess passive and active ankle stiffness during quiet upright stance. AB - Both passive and active ankle torque contribute to postural stability during quiet upright stance, yet directly measuring their relative contributions is difficult. Here, a new method was developed to estimate passive and active ankle stiffness (ST) and damping (DA). In contrast to earlier approaches, the proposed method does not require external mechanical or sensory perturbations. Instead, the method is based on the assumption that upright stance is intermittently controlled, and that active ankle torque is in-phase coherent with ankle angular acceleration. Thus, identifying the local maxima of ankle angular accelerations facilitates the identification of time windows that include substantial active ankle torque. After identifying these local maxima and associated windows, estimates of passive and active ankle ST and DA were obtained using linear regression analyses. Consistent with earlier work, passive ankle torque was estimated to account for 94-97% of the total ankle torque, and to have linear relationships with ankle angle and angular velocity. Predicted values of passive and active ankle stiffness were also consistent with earlier reports. This new approach may be a useful tool to efficiently investigate passive and active joint stiffness during quiet upright stance. PMID- 26547841 TI - Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells. AB - BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1alpha) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1alpha is dependent on Prolyl hydroxylase (PHD 1-3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1alpha regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1alpha protein and transcriptional activity in metastatic melanoma and reduce its invasive potential. METHODS: HIF-1alpha protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter gene activity. Melanoma cells were treated with ascorbic acid (AA) and ascorbate 2-phosphate (A2P) to assess their ability to reduce HIF-1alpha accumulation and activity. siRNA was used to deplete cellular PHD2 in order to evaluate this effect on AA's ability to lower HIF 1alpha levels. A2P's effect on invasive activity was measured by the Matrigel invasion assay. Data was analyzed by One-way ANOVA with Tukey's multiple comparisons test, or Student-T test as appropriate, with p < .05 considered significant. RESULTS: Supplementation with both AA and A2P antagonized normoxic as well as cobalt chloride- and PHD inhibitor ethyl 3, 4-dihydroxybenzoate induced HIF-1alpha protein stabilization and transcriptional activity. Knockdown of the PHD2 isoform with siRNA did not impede the ability of AA to reduce normoxic HIF-1alpha protein. Additionally, reducing HIF-1alpha levels with A2P resulted in a significant reduction in the ability of the melanoma cells to invade through Matrigel. CONCLUSION: These studies suggest a positive role for AA in regulating HIF-1alpha in melanoma by demonstrating that supplementation with either AA, or its oxidation-resistant analog A2P, effectively reduces HIF-1alpha protein and transcriptional activity in metastatic melanoma cells. Our data, while supporting the function of AA as a necessary cofactor for PHD and likely FIH activity, also suggests a potential non-PHD/FIH role for AA in HIF-1alpha regulation by its continued ability to reduce HIF-1alpha in the presence of PHD inhibition. The use of the oxidation-resistant AA analog, A2P, to reduce the ability of HIF-1alpha to promote malignant progression in melanoma cells and enhance their response to therapy warrants further investigation. PMID- 26547843 TI - Detecting the perception of illusory spatial boundaries: Evidence from distance judgments. AB - Spatial boundaries demarcate everything from the lanes in our roadways to the borders between our countries. They are fundamental to object perception, spatial navigation, spatial memory, spatial judgments, and the coordination of our actions. Although explicit spatial boundaries formed by physical structures comprise many of the actual boundaries we encounter, implicit and permeable spatial boundaries are pervasive. The prevailing paradigm for detecting implicit spatial boundaries relies on memory-based distance and location judgments. One possibility is that these biases in spatial memory may be attributable to initial biases in spatial perception, but the extent to which implicit spatial boundaries bias spatial perception remains unknown. An approach for detecting the perception of implicit spatial boundaries would be to infer it through known systematic biases in memory-based distance judgments. We harnessed known biases in memory based distance judgments to infer perception of spatial boundaries by probing the extent to which distances were overestimated across potential spatial boundaries. Results suggest that participants perceived potential spatial boundaries as illusory spatial boundaries leading to biased judgments of distance. A control group eliminated simple two-dimensional distance cues as responsible for this bias. This bias provides a novel method to detect the perception of illusory spatial boundaries. PMID- 26547844 TI - Utilization of a Pharmacy Clinical Surveillance System for Pharmacist Alerting and Communication at a Tertiary Academic Medical Center. AB - The objective of this analysis is to describe the utilization metrics of a pharmacy clinical surveillance system (PCSS) at a tertiary, academic medical center.We performed a retrospective database analysis assessing rule-based alerts (RBA), interventions and pharmacist communication notes documented in the PCSS from January 1, 2014 to December 31, 2014. Reports were generated on 92 unique RBAs sent to clinicians for evaluation. Metrics assessed included the number of RBAs that were triggered, clinically evaluated, intervened on by pharmacists, and therapeutic category of interventions. Pharmacy communication notes were also evaluated.A total of 399,979 RBAs were triggered through the PCSS. During that time, pharmacists documented a total of 17,733 interventions. The most common RBAs were related to lab abnormalities (132,487; 33 %) and anticoagulation/antiplatelet therapy (126,425; 32.1 %). Interventions were most frequently related to RBAs regarding anticoagulation/antiplatelet therapy (6412; 36 %) and antimicrobial therapy (3320; 19 %). Pharmacist communication was most commonly related to clarification of medication and lab orders, and therapeutic drug monitoring.Based on utilization metrics presented, the implementation of a PCSS has successfully generated RBAs to aid pharmacists in clinical practice and improved departmental documentation and communication. Further analysis is warranted to assess the impact of the RBAs, interventions, and communication notes on outcomes such as hospital cost and adverse drug events. PMID- 26547845 TI - A Method to Differentiate Mild Cognitive Impairment and Alzheimer in MR Images using Eigen Value Descriptors. AB - Automated analysis and differentiation of mild cognitive impairment and Alzheimer's condition using MR images is clinically significant in dementic disorder. Alzheimer's Disease (AD) is a fatal and common form of dementia that progressively affects the patients. Shape descriptors could better differentiate the morphological alterations of brain structures and aid in the development of prospective disease modifying therapies. Ventricle enlargement is considered as a significant biomarker in the AD diagnosis. In this work, a method has been proposed to differentiate MCI from the healthy normal and AD subjects using Laplace-Beltrami (LB) eigen value shape descriptors. Prior to this, Reaction Diffusion (RD) level set is used to segment the ventricles in MR images and the results are validated against the Ground Truth (GT). LB eigen values are infinite series of spectrum that describes the intrinsic geometry of objects. Most significant LB shape descriptors are identified and their performance is analysed using linear Support Vector Machine (SVM) classifier. Results show that, the RD level set is able to segment the ventricles. The segmented ventricles are found to have high correlation with GT. The eigen values in the LB spectrum could show distinction in the feature space better than the geometric features. High accuracy is observed in the classification results of linear SVM. The proposed automated system is able to distinctly separate the MCI from normal and AD subjects. Thus this pipeline of work seems to be clinically significant in the automated analysis of dementic subjects. PMID- 26547846 TI - Applications of Multi-Channel Safety Authentication Protocols in Wireless Networks. AB - People can use their web browser or mobile devices to access web services and applications which are built into these servers. Users have to input their identity and password to login the server. The identity and password may be appropriated by hackers when the network environment is not safe. The multiple secure authentication protocol can improve the security of the network environment. Mobile devices can be used to pass the authentication messages through Wi-Fi or 3G networks to serve as a second communication channel. The content of the message number is not considered in a multiple secure authentication protocol. The more excessive transmission of messages would be easier to collect and decode by hackers. In this paper, we propose two schemes which allow the server to validate the user and reduce the number of messages using the XOR operation. Our schemes can improve the security of the authentication protocol. The experimental results show that our proposed authentication protocols are more secure and effective. In regard to applications of second authentication communication channels for a smart access control system, identity identification and E-wallet, our proposed authentication protocols can ensure the safety of person and property, and achieve more effective security management mechanisms. PMID- 26547847 TI - Implementation of an Embedded Web Server Application for Wireless Control of Brain Computer Interface Based Home Environments. AB - Brain Computer Interface (BCI) based environment control systems could facilitate life of people with neuromuscular diseases, reduces dependence on their caregivers, and improves their quality of life. As well as easy usage, low-cost, and robust system performance, mobility is an important functionality expected from a practical BCI system in real life. In this study, in order to enhance users' mobility, we propose internet based wireless communication between BCI system and home environment. We designed and implemented a prototype of an embedded low-cost, low power, easy to use web server which is employed in internet based wireless control of a BCI based home environment. The embedded web server provides remote access to the environmental control module through BCI and web interfaces. While the proposed system offers to BCI users enhanced mobility, it also provides remote control of the home environment by caregivers as well as the individuals in initial stages of neuromuscular disease. The input of BCI system is P300 potentials. We used Region Based Paradigm (RBP) as stimulus interface. Performance of the BCI system is evaluated on data recorded from 8 non disabled subjects. The experimental results indicate that the proposed web server enables internet based wireless control of electrical home appliances successfully through BCIs. PMID- 26547848 TI - Analysis of Muscle Fatigue Progression using Cyclostationary Property of Surface Electromyography Signals. AB - Analysis of neuromuscular fatigue finds various applications ranging from clinical studies to biomechanics. Surface electromyography (sEMG) signals are widely used for these studies due to its non-invasiveness. During cyclic dynamic contractions, these signals are nonstationary and cyclostationary. In recent years, several nonstationary methods have been employed for the muscle fatigue analysis. However, cyclostationary based approach is not well established for the assessment of muscle fatigue. In this work, cyclostationarity associated with the biceps brachii muscle fatigue progression is analyzed using sEMG signals and Spectral Correlation Density (SCD) functions. Signals are recorded from fifty healthy adult volunteers during dynamic contractions under a prescribed protocol. These signals are preprocessed and are divided into three segments, namely, non fatigue, first muscle discomfort and fatigue zones. Then SCD is estimated using fast Fourier transform accumulation method. Further, Cyclic Frequency Spectral Density (CFSD) is calculated from the SCD spectrum. Two features, namely, cyclic frequency spectral area (CFSA) and cyclic frequency spectral entropy (CFSE) are proposed to study the progression of muscle fatigue. Additionally, degree of cyclostationarity (DCS) is computed to quantify the amount of cyclostationarity present in the signals. Results show that there is a progressive increase in cyclostationary during the progression of muscle fatigue. CFSA shows an increasing trend in muscle fatiguing contraction. However, CFSE shows a decreasing trend. It is observed that when the muscle progresses from non-fatigue to fatigue condition, the mean DCS of fifty subjects increases from 0.016 to 0.99. All the extracted features found to be distinct and statistically significant in the three zones of muscle contraction (p < 0.05). It appears that these SCD features could be useful in the automated analysis of sEMG signals for different neuromuscular conditions. PMID- 26547849 TI - A Method to Find Generic Thresholds for Identifying Relevant Physical Activity Events in Sensor Data. AB - The increasing use of wearable actimetry devices in cohort studies can provide a deep and objective insight in physical activity (PA) patterns. For reliable and reproducible pattern recognition, and to minimize the influence of specific device characteristics, there is a need for a generic method to identify relevant PA events in sensor data sets on the basis of comprehensive features such as PA duration and intensity. The objectives of this paper are to present a method to identify universal event detection thresholds for such parameters, and to attempt to find stable meta-clusters of PA behaviour. PA events of 5, 10, 20 and 30 min with low, medium and high intensity thresholds found in literature and intensity deciles were computed for a random sample (N = 100) of the NHANES 2005-06 accelerometer data set (N = 7457). On the basis of all combinations of the above, activity events were detected, and parameters mean duration, mean intensity and event regularity were computed. Results were clustered using x-Means clustering and visualized for 5-, 10-, 20-, and 30-min events. Stable clustering results are obtained with intensity thresholds up to the 8th decile and for event durations up to 10 min. Two stable meta-clusters were detected: 'irregularly active' (intensity at 52nd percentile) and 'regularly active' (intensity at 42nd percentile). Distinct generic thresholds could be identified and are proposed. They may prove useful for further investigations of similar actimetry data sets, minimising the influence of specific device characteristics. The results also confirm that distinct PA event patterns - including event regularity - can be identified using wearable sensor devices, especially when regarding low intensity, short-term activities which do not correspond to current PA recommendations. Further research is necessary to evaluate actual associations between sensor-based PA parameters and health outcome. The author identified generic intensity and duration thresholds for analysing objective PA data from wearable devices. This may contribute to further analyses of PA patterns along with their relations with health outcome parameters. PMID- 26547850 TI - Predictive / Reactive Planning and Scheduling of a Surgical Suite with Emergency Patient Arrival. AB - This paper surveys the problem of predictive / reactive scheduling of an integrated operating theatre with two types of demand for surgery: 1) elective or known demand; 2) emergency or uncertain demand. The stochastic arrival of emergency patients with uncertain surgery time enforces the scheduler to react to disruption and modify scheduling plan of elective patients. We focus on this predictive / reactive scheduling problem which has not been investigated in such way before. As in hospitals, at the time of occurrence a disruption in a surgical suite, the scheduler has not enough time to make the best decision; we propose a new approach based on two-stage stochastic programming model with recourse which determines the best recourse strategy in advance of any disruption occurrence. Using the proposed approach, the primary schedule is generated in such a way that it can absorb disruption with minimum effect on planned elective surgeries. For the first time in operating theatre planning, two new significant sets of performance measures comprising "robustness" and "stability" measures are considered in generation of primary schedule which will be shown to be of great importance in efficiency of surgical suite planning. Computational experiments performed on sets of generated problem based on the data obtained from a non profit hospital. In order to demonstrate efficiency of the proposed method, computational results of the proposed approach are compared with classic approach. PMID- 26547851 TI - Presence of DNA methyltransferase activity and CpC methylation in Drosophila melanogaster. AB - Drosophila melanogaster lacks DNMT1/DNMT3 based methylation machinery. Despite recent reports confirming the presence of low DNA methylation in Drosophila; little is known about the methyltransferase. Therefore, in this study, we have aimed to investigate the possible functioning of DNA methyltransferase in Drosophila. The 14 K oligo microarray slide was incubated with native cell extract from adult Drosophila to check the presence of the methyltransferase activity. After incubation under appropriate conditions, the methylated oligo sequences were identified by the binding of anti 5-methylcytosine monoclonal antibody. The antibody bound to the methylated oligos was detected using Cy3 labeled secondary antibody. Methylation sensitive restriction enzyme mediated PCR was used to assess the methylation at a few selected loci identified on the array. It could be seen that a few of the total oligos got methylated under the assay conditions. Analysis of methylated oligo sequences provides evidence for the presence of de novo methyltransferase activity and allows identification of its sequence specificity in adult Drosophila. With the help of methylation sensitive enzymes we could detect presence of CpC methylation in the selected genomic regions. This study reports presence of an active DNA methyltransferase in adult Drosophila, which exhibits sequence specificity confirmed by presence of asymmetric methylation at corresponding sites in the genomic DNA. It also provides an innovative approach to investigate methylation specificity of a native methyltransferase. PMID- 26547852 TI - A Comprehensive Review on L-Asparaginase and Its Applications. AB - L-asparaginase (LA) catalyzes the degradation of asparagine, an essential amino acid for leukemic cells, into ammonia and aspartate. Owing to its ability to inhibit protein biosynthesis in lymphoblasts, LA is used to treat acute lymphoblastic leukemia (ALL). Different isozymes of this enzyme have been isolated from a wide range of organisms, including plants and terrestrial and marine microorganisms. Pieces of information about the three-dimensional structure of L-asparaginase from Escherichia coli and Erwinia sp. have identified residues that are essential for catalytic activity. This review catalogues the major sources of L-asparaginase, the methods of its production through the solid state (SSF) and submerged (SmF) fermentation, purification, and characterization as well as its biological roles. In the same breath, this article explores both the past and present applications of this important enzyme and discusses its future prospects. PMID- 26547853 TI - Cloning, Expression, Mutagenesis Library Construction of Glycerol Dehydratase, and Binding Mode Simulation of Its Reactivase with Ligands. AB - The production of 1, 3-propanediol (1, 3-PD) and 3-hydroxypropionaldehyde (3-HPA) by enzyme reaction has been a hot field, and glycerol dehydratase (GDHt) is the key and rate-limiting enzyme involved in their biosynthesis. The gldABC gene encoding GDHt was cloned from Klebsiella pneumoniae, and the activity of the corresponding proteins expressed extracellularly and intracellularly was 6.8 and 3.2 U/mg, respectively, about six and three times higher than that of the wild strain. The change of amino acids for the beta subunit can adjust the length of the Co-N bond and affect the homolysis rate of the Co-C bond to change GDHt activity. The expression plasmid, pET-32a-gldAC (containing no gldB which encodes the beta subunit of GDHt), was constructed to build the mutagenesis library to improve the GDHt activity. The binding models of glycerol dehydratase reactivation factor (GDHtR) with ATP, CTP, or GTP were simulated by semi-flexible docking, respectively, and there was almost no difference between them. This research provided the basis for studying the quantitative structure-activity relationships between GDHtR and its ligands, as well as searching inexpensive ligands to replace ATP. These results and methods are of great use in economical and highly efficient production of 3-HPA and 1, 3-PD by the enzyme method. PMID- 26547854 TI - Nocardia zapadnayensis sp. nov., isolated from soil. AB - A novel Gram-stain positive, rod-shaped, non-motile and mycolic acid containing strain, FMN18(T), isolated from soil, was characterised using a polyphasic approach. The organism showed a combination of morphological, biochemical, physiological and chemotaxonomic properties that were consistent with its classification in the genus Nocardia and it formed a phyletic line in the Nocardia 16S rRNA gene tree. The cell wall contained meso-diaminopimelic acid (type IV) and whole cell sugars were galactose, glucose, arabinose and ribose. The predominant menaquinone was MK-8(H4omega-cyclo). The major phospholipids are diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. Major fatty acids are C16:0, 10-methyl C18:0 (TBSA), C18:1 cis9 and C16:1 trans9. These chemotaxonomic traits are in good agreement with those known for representatives of the genus Nocardia. The phylogenetic analysis based on the 16S rRNA gene sequence of strain FMN18(T) showed it to be closely related to Nocardia grenadensis GW5-5797(T) (99.2 %), Nocardia speluncae N2-11(T) (99.1 %), Nocardia jinanensis 04-5195(T) (99.0 %) and Nocardia rhamnosiphila 202GMO(T) (98.3 %). The phylogenetic analysis based on the gyrB gene sequence of strain FMN18(T) showed it to be closely related to N. rhamnosiphila 202GMO(T) (99.0 %), N. grenadensis DSM 45869(T) (96.6 %), N. jinanensis DSM 45048(T) (93.1 %), N. carnea IFM 0237(T) (89.7 %) and N. speluncae DSM 45078(T) (89.1 %). A combination of DNA-DNA hybridization results and phenotypic properties demonstrated that strain FMN18(T) was clearly distinguished from all closely related Nocardia species. It is proposed that the organism be classified as representing a novel species of the genus Nocardia, for which the name Nocardia zapadnayensis (type strain FMN18(T) = DSM 45872(T) = KCTC 29234(T)) is proposed. PMID- 26547855 TI - Age-Related Changes in Hepatic Function: An Update on Implications for Drug Therapy. AB - The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people's responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of 'start low, go slow' should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians. PMID- 26547856 TI - The Effect of Melatonin on Benzodiazepine Discontinuation and Sleep Quality in Adults Attempting to Discontinue Benzodiazepines: A Systematic Review and Meta Analysis. AB - BACKGROUND: Abrupt discontinuation of benzodiazepines often results in side effects including anxiety and insomnia, which can be barriers to discontinuation among long-term users. Melatonin improves the onset, duration, and quality of sleep. By preventing insomnia in those attempting to discontinue benzodiazepines, melatonin may facilitate benzodiazepine discontinuation. OBJECTIVES: The primary objective was to determine the effect of melatonin compared with placebo on benzodiazepine discontinuation in adults attempting to discontinue benzodiazepines. The secondary objective was to determine the effect of melatonin on sleep quality in this population. METHODS: We searched PubMed, MEDLINE, EMBASE, PsychINFO, and ClinicalTrials.gov from inception to November 2014. We included randomized controlled trials published in English comparing melatonin with placebo that reported benzodiazepine discontinuation or sleep quality. Two reviewers independently screened trials, extracted data, and assessed the risk of bias. RESULTS: We included six trials randomizing 322 participants. The mean age of participants was approximately 64 years. The trials used varied tapering strategies to discontinue benzodiazepines over 4-10 weeks while using melatonin. Melatonin had no effect on the odds of successfully discontinuing benzodiazepines (odds ratio 0.72, 95% confidence interval 0.21-2.41, p = 0.59). There was important heterogeneity among the trials (I (2) = 76%). The effect of melatonin on sleep quality was inconsistent. CONCLUSIONS: Melatonin had no effect on benzodiazepine discontinuation while the effect of melatonin on sleep quality was inconsistent. We cannot rule out a role of melatonin in improving benzodiazepine discontinuation or sleep quality owing to imprecise effect estimates. Larger, well-designed, and reported randomized controlled trials may provide more valid and precise estimates of the effect of melatonin on these outcomes. PMID- 26547857 TI - Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression. AB - Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care. PMID- 26547858 TI - Testicular acid phosphatase induces odontoblast differentiation and mineralization. AB - Odontoblasts differentiate from dental mesenchyme during dentin formation and mineralization. However, the molecular mechanisms controlling odontoblast differentiation remain poorly understood. Here, we show that expression of testicular acid phosphatase (ACPT) is restricted in the early stage of odontoblast differentiation in proliferating dental mesenchymal cells and secretory odontoblasts. ACPT is expressed earlier than tissue-nonspecific alkaline phosphatase (TNAP) and partly overlaps with TNAP in differentiating odontoblasts. In MDPC-23 odontoblastic cells, expression of ACPT appears simultaneously with a decrease in beta-catenin activity and is abolished with the expression of Phex and Dsp. Knockdown of ACPT in MDPC-23 cells stimulates cell proliferation together with an increase in active beta-catenin and cyclin D1. In contrast, the overexpression of ACPT suppresses cell proliferation with a decrease in active beta-catenin and cyclin D1. Expression of TNAP, Osx, Phex and Dsp is reduced by knockdown of ACPT but is enhanced by ACPT overexpression. When ACPT is blocked with IgG, alkaline phosphatase activity is inhibited but cell proliferation is unchanged regardless of ACPT expression. These findings suggest that ACPT inhibits cell proliferation through beta-catenin-mediated signaling in dental mesenchyme but elicits odontoblast differentiation and mineralization by supplying phosphate during dentin formation. Thus, ACPT might be a novel candidate for inducing odontoblast differentiation and mineralization for dentin regeneration. PMID- 26547859 TI - Osteogenic stimulation of human adipose-derived stem cells by pre-treatment with fibroblast growth factor 2. AB - Although adipose-derived stem cells (ADSCs) have many advantageous traits compared with other postnatal stem cells, the consensus is that their differentiation potential must be improved to allow their practical utilization. During the in vitro expansion of human ADSCs (hADSCs), pre-treatment of fibroblast growth factor 2 (FGF2) not only induced an increase of approximately 44-fold in cell number at passage 7 but also augmented the differentiation potential of hADSCs. The effect of FGF2-induced cell preconditioning was evaluated by in vitro and in vivo osteogenesis after pre-treatment with various concentrations of FGF2 (0, 5, 25 ng/ml). FGF2-pre-treated hADSCs showed enhanced in vitro osteogenesis. An evaluation of in vivo osteogenic potential with an ectopic bone model showed that FGF2-preconditioned hADSCs produced an abundant osteoid/bone matrix and the effect was dependent on the concentration of FGF2 pre treatment; bone matrix formation by control hADSCs was virtually non-existent. FGF2-pre-treated hADSCs also showed enhanced in vitro chondrogenesis, whereas no significant difference was observed in adipogenic potential. Pre-treatment of hADSCs with FGF2 induced an increase in the expression of osteogenic markers such as Cbfa1/Runx2 and alkaline phosphatase and in the expression of beta-catenin. These results suggest that FGF2 plays a highly beneficial role in the preconditioning of ADSCs for musculoskeletal tissue engineering. PMID- 26547860 TI - Predictors of Venous Thromboembolism in Patients with Glioblastoma. AB - To evaluate different risk factors associated with development of venous thromboembolism (VTE) in patients with Glioblastoma (GBM). A retrospective chart review was performed to include patients diagnosed with GBM from 2001 to 2011. Cases (n = 162) were defined as patients with GBM who developed VTE after diagnosis of GBM. Controls (n = 840) were defined as patients with GBM with no history of VTE. Data was collected for multiple variables including age, gender, race, length of hospital stay after brain biopsy, total number of hospital admissions unrelated to VTE, Karnofsky Performance Status (KPS), use of Bevacizumab and any bleeding episodes. Patients with GBM who had VTE had poorer KPS scores, with the majority (57%) being in between 40 and 70, as compared to the controls where majority (82%) had better performance (KPS 80-100). For every one year increase in age, the odds of developing VTE increased by 3% (OR 1.03, 95%CI 1.02-1.04, p < 0.001) with the mean age being 61.8 +/- 11.4 years. GBM patients who developed a VTE were found to have greater number of hospital admissions (OR 1.43, 95%CI 1.33-1.53, p < 0.001) and longer stays in hospital after GBM biopsy (OR 1.14, 95%CI 1.09-1.18, p < 0.001). Patients receiving Bevacizumab were more likely to develop VTE (OR 1.79, 95%CI 1.21-2.64, p < 0.001) and were more likely to have a bleed (OR 3.78, 95% CI 2.70-5.30, p < 0.001). Patients with GBM are at a higher risk of developing VTE. The risk is higher in older patients who require multiple hospital admissions, longer duration of hospital stays related to GBM biopsy, and in patients with lower KPS scores. Bevacizumab use is related to a higher incidence of VTE as well as bleeds. This study suggests that a more aggressive strategy for VTE prophylaxis should be considered in GBM patients with risk factors for VTE. PMID- 26547861 TI - ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility. AB - Gastric cancer is a major leading cause of cancer-related death in both sexes in Europe. The role of autophagy process in carcinogenesis remains unclear and there is increasing evidence that Helicobacter pylori is a key player in modulating autophagy in gastric carcinogenesis. The aim of this study was to assess the potential association of ATG16L1 T300A polymorphism with susceptibility of gastric cancer, and further to analyze the expression profile of ATG16L1 gene in paired tumoral and peritumoral gastric tissue. A total of 108 patients diagnosed with gastric cancer and 242 healthy controls were enrolled. ATG16L1 T300A polymorphism was detected using TaqMan genotyping assay containing primers and specific probes for A and G allele, respectively. ATG16L1 mRNA level was evaluated in 34 paired tumoral and peritumoral tissues using qRT-PCR. We found a significant association for both carriers of AG (OR 0.52, 95% CI: 0.30-0.91, p = 0.02) and GG genotype (OR 0.53, 95% CI: 0.28-0.98, p = 0.043), these were at a lower risk for gastric cancer when compared with the wild-type AA genotype. The strongest association was observed in a dominant model, the carriers of G allele were protected against gastric cancer (OR 0.52, 95% CI: 0.13-0.88, p = 0.013). In a stratified analyse, the association was limited to non-cardia type and intestinal type. ATG16L1 gene expression was detected in both tumor and peritumoral tissues, with the mRNA-ATG16L1 levels significantly higher in tumor sample. Our results suggest that ATG16L1 T300A polymorphism may be associated with gastric carcinogenesis. PMID- 26547862 TI - Treatment of colonic transplantation tumor-bearing mice with a high-dose aspirin in a short period of time. PMID- 26547863 TI - Sacral malformations: use of imaging to optimise sacral nerve stimulation. AB - INTRODUCTION: The success of sacral nerve stimulation, a common treatment for pelvic floor disorders, depends on correct placement of the electrodes through the sacral foramina. When the bony anatomy and topography of the sacrum and sacral spinal nerves are intact, this is easily achieved; where sacral anomalies exist, it can be challenging. A better understanding of common sacral malformations can improve the success of sacral nerve stimulation (SNS) electrode placement. MATERIAL AND METHODS: We reviewed 998 consecutive MRI scans performed to investigate low back pain in patients who had undergone CT and/or X-ray. RESULTS: Congenital sacral malformations were found in 24.1%, the most common being sacral meningeal cysts (16%) and spina bifida occulta (9.9%). Others were lumbosacral transitional vertebrae (2.5%), anterior occult meningocele (0.5%), partial sacral agenesis (0.2%) and vertebral dysplasia of S1 (0.2%). CONCLUSION: This radiologic review uncovered a high incidence of sacral malformations, and most were asymptomatic. All surgeons who perform SNS should have a basic understanding of sacral malformations, their incidence and effect on foraminal anatomy. Imaging will aid procedural planning. PMID- 26547864 TI - Idiopathic erythrocytosis: a study of a large cohort with a long follow-up. AB - Idiopathic erythrocytosis (IE) is an absolute erythrocytosis with no known cause, diagnosed by exclusion of primary and secondary erythrocytosis. Familial erythrocytosis (FE) is a rare disease and as the rare patients with JAK2-wild type polycythemia vera (PV) may be misdiagnosed as IE. We compared 78 patients with IE, 21 with FE and 136 with PV in the effort to identify simple features capable of discriminating between them. FE patients were younger at diagnosis either than IE and PV (p < 0.001); IE and FE had lower WBC, platelet counts and higher serum EPO levels, and had splenomegaly and thrombotic events less frequently than PV patients. Phlebotomies to obtain a haematocrit lower than 45 % induce platelet count increase in 70 % of PV but not in IE. Mainly in men, normal spleen, normal platelet counts and no history of thrombosis at diagnosis argue against PV; diagnosis of IE could be supported by means of a cycle of venesection to see how it affects their platelet count. No simple data capable of distinguishing between IE and FE were identified; therefore, a case of sporadic erythrocytosis in a young patient should be investigated as a possible genetic cause. PMID- 26547865 TI - Is an early retirement offer good for your health? Quasi-experimental evidence from the army. AB - This paper studies empirically the consequences on health of an early retirement offer. To this end we use a targeted retirement offer to military officers 55 years of age or older. Before the offer was implemented, the normal retirement age in the Swedish defense was 60 years of age. Estimating the effect of the offer on individuals' health within the age range 56-70, we find support for a reduction in both mortality and in inpatient care as a consequence of the early retirement offer. Increasing the mandatory retirement age may thus not only have positive government income effects but also negative effects on increasing government health care expenditures. PMID- 26547866 TI - Medication Adherence Following Acute Coronary Syndrome: Does One Size Fit All? AB - Guideline-based management of acute coronary syndrome (ACS) is well established, yet some may challenge that strict implementation of guideline recommendations can limit the individualization of therapy. The use of all recommended medications following ACS places a high burden of responsibility and cost on patients, particularly when these medications have not been previously prescribed. Without close attention to avoiding non-adherence to these medications, the full benefits of the guideline recommendations will not be realized in many patients. Using a case example, we discuss how the recognition of adherence barriers can be an effective and efficient process for identifying patients at risk of non-adherence following ACS. For those identified as at risk, the World Health Organization's model of adherence barriers is explored as a potentially useful tool to assist with individualization of therapy and promotion of adherence. PMID- 26547867 TI - Theta burst stimulation improves overt visual search in spatial neglect independently of attentional load. AB - Visual neglect is considerably exacerbated by increases in visual attentional load. These detrimental effects of attentional load are hypothesised to be dependent on an interplay between dysfunctional inter-hemispheric inhibitory dynamics and load-related modulation of activity in cortical areas such as the posterior parietal cortex (PPC). Continuous Theta Burst Stimulation (cTBS) over the contralesional PPC reduces neglect severity. It is unknown, however, whether such positive effects also operate in the presence of the detrimental effects of heightened attentional load. Here, we examined the effects of cTBS on neglect severity in overt visual search (i.e., with eye movements), as a function of high and low visual attentional load conditions. Performance was assessed on the basis of target detection rates and eye movements, in a computerised visual search task and in two paper-pencil tasks. cTBS significantly ameliorated target detection performance, independently of attentional load. These ameliorative effects were significantly larger in the high than the low load condition, thereby equating target detection across both conditions. Eye movement analyses revealed that the improvements were mediated by a redeployment of visual fixations to the contralesional visual field. These findings represent a substantive advance, because cTBS led to an unprecedented amelioration of overt search efficiency that was independent of visual attentional load. PMID- 26547868 TI - [Mass gatherings: A new public health challenge in Spain]. PMID- 26547869 TI - In vivo precision of conventional and digital methods for obtaining quadrant dental impressions. AB - OBJECTIVES: Quadrant impressions are commonly used as alternative to full-arch impressions. Digital impression systems provide the ability to take these impressions very quickly; however, few studies have investigated the accuracy of the technique in vivo. The aim of this study is to assess the precision of digital quadrant impressions in vivo in comparison to conventional impression techniques. MATERIALS AND METHODS: Impressions were obtained via two conventional (metal full-arch tray, CI, and triple tray, T-Tray) and seven digital impression systems (Lava True Definition Scanner, T-Def; Lava Chairside Oral Scanner, COS; Cadent iTero, ITE; 3Shape Trios, TRI; 3Shape Trios Color, TRC; CEREC Bluecam, Software 4.0, BC4.0; CEREC Bluecam, Software 4.2, BC4.2; and CEREC Omnicam, OC). Impressions were taken three times for each of five subjects (n = 15). The impressions were then superimposed within the test groups. Differences from model surfaces were measured using a normal surface distance method. Precision was calculated using the Perc90_10 value. The values for all test groups were statistically compared. RESULTS: The precision ranged from 18.8 (CI) to 58.5 MUm (T-Tray), with the highest precision in the CI, T-Def, BC4.0, TRC, and TRI groups. The deviation pattern varied distinctly depending on the impression method. Impression systems with single-shot capture exhibited greater deviations at the tooth surface whereas high-frame rate impression systems differed more in gingival areas. Triple tray impressions displayed higher local deviation at the occlusal contact areas of upper and lower jaw. CONCLUSIONS: Digital quadrant impression methods achieve a level of precision, comparable to conventional impression techniques. However, there are significant differences in terms of absolute values and deviation pattern. CLINICAL RELEVANCE: With all tested digital impression systems, time efficient capturing of quadrant impressions is possible. The clinical precision of digital quadrant impression models is sufficient to cover a broad variety of restorative indications. Yet the precision differs significantly between the digital impression systems. PMID- 26547870 TI - Influence of surface treatment on the in-vitro fracture resistance of zirconia based all-ceramic anterior crowns. AB - OBJECTIVES: The purpose of this study was to assess the effect of surface treatment on the fracture resistance of zirconia-based all-ceramic anterior crowns. METHODS: Sixty-four zirconia-based all-ceramic anterior crowns, veneered by use of a press-on technique, were produced. For 48 crowns intraoral adjustment was simulated (A-group), 16 crowns remained unadjusted (WA-group). The adjusted area was then treated in three ways: 1. no further surface treatment; 2. polishing, with irrigation, using polishers interspersed with diamond grit for ceramics; and 3. polishing and glaze firing. Half of the specimens were loaded until fracture in an universal testing device without artificial ageing; the other crowns underwent thermocycling and chewing simulation before ultimate-load testing. Explorative statistical analysis was performed by use of non-parametric and parametric tests. In addition, fracture-strength tests according to ISO 6872 were performed for veneer ceramic subjected to the different surface treatments. Finite element analysis was also conducted for the crowns, and surface roughness was measured. RESULTS: Crowns in the A-group were more sensitive to aging than crowns in the WA-group (p=0.038). Although both polishing and glaze firing slightly improved the fracture resistance of the specimens, the fracture resistance in the WA-group (initial fracture resistance (IFR): 652.0 +/- 107.7N, remaining fracture resistance after aging (RFR): 560.6 +/- 233.3N) was higher than the fracture resistance in the A-group (polished: IFR: 477.9 +/- 108.8N, RFR: 386.0 +/- 218.5N; glaze firing: IFR: 535.5 +/- 128.0N, RFR: 388.6 +/- 202.2N). Surface roughness without adjustment was Ra=0.1 MUm; for adjustment but without further treatment it was Ra=1.4 MUm; for adjustment and polishing it was Ra=0.3 MUm; and for adjustment, polishing, and glazing it was Ra=0.6 MUm. Stress distributions obtained by finite element analysis in combination with fracture strength tests showed that fractures most probably originated from the occlusal surface. SIGNIFICANCE: To improve fracture resistance and reduce the incidence of failure, extensive occlusal adjustment of veneered anterior zirconia restorations should be avoided. Neither polishing nor glazing could restore the fracture resistance to the level maintained with unadjusted crowns. PMID- 26547871 TI - Non-invasive ventilation in the treatment of acute and chronic exacerbated respiratory failure: What to expect outside the critical care units? PMID- 26547872 TI - Growth inhibition and possible mechanism of oleamide against the toxin-producing cyanobacterium Microcystis aeruginosa NIES-843. AB - Oleamide, a fatty acid derivative, shows inhibitory effect against the bloom forming cyanobacterium Microcystis aeruginosa. The EC50 of oleamide on the growth of M. aeruginosa NIES-843 was 8.60 +/- 1.20 mg/L. In order to elucidate the possible mechanism of toxicity of oleamide against M. aeruginosa, chlorophyll fluorescence transient, cellular ultrastructure, fatty acids composition and the transcription of the mcyB gene involved in microcystins synthesis were studied. The results of chlorophyll fluorescence transient showed that oleamide could destruct the electron accepting side of the photosystem II of M. aeruginosa NIES 843. Cellular ultrastructure examination indicated that the destruction of fatty acid constituents, the distortion of thylakoid membrane and the loss of integrity of cell membrane were associated with oleamide treatment and concentration. The damage of cellular membrane increased the release of microcystins from intact cells into the medium. Results presented in this study provide new information on the possible mechanisms involved and potential utilization of oleamide as an algicide in cyanobacterial bloom control. PMID- 26547873 TI - Biological properties of extremely acidic cyanide-laced mining waste. AB - With respect to acidic, cyanide-laced tailings, the data about in situ toxicity and biological activity in highly polluted environment are often lacking. The aim of this study was to assess the microbial characteristics, composition of oribatid mite species, and level of genotoxic impact on plants in the area of inactive tailings pond (Horna Ves, Kremnica region). Sampling of the tailings, soils and selected plant species was carried out in spring of 2012. Trace element analysis (inductively coupled plasma emission and mass spectrometry) showed that concentration of Pb, Zn, and Cu in the tailings is approximately in thousands of ppm (mg kg(-1)). Amount of lead exceeded 16,000 mg kg(-1), which is perceived as the biggest threat with respect to possible toxicity. The risk is accentuated by extremely acidic pH of the tailings material which approached 2. In such conditions great mobility of (divalent) heavy metal cations is expected. The total cyanide concentration in the tailings was 472 mg kg(-1). Results of performed tests and measurements suggest that microbial activity at the tailings site (and its close environment) is hampered markedly. In the sludge material we detected low abundance of soil bacteria (2.08 * 10(4) CFU) and predominance of slowly growing K-strategists. On the other hand, the content of microbial C in the sludge sample was not too low, considering its extreme acidity and high amount of risk elements. In the same sample, just one mite species, Oppiella (O.) uliginosa (Willmann 1919), was identified. Also in case of the dam site the abundance of mites was considerably lower in comparison to reference sample. Values of Oribatida abundance were in positive correlation with values of microbial biomass carbon. Results of the pollen grain abortivity test, applied in situ on chosen plant species, indicated substantial presence of genotoxicity in the environment. Total induction index of tailings pond reached 3.59(+/-2.4) which expresses also total load of locality, comparing to natural biotope. In case of the technogenic sediment, the value was more than three times higher. PMID- 26547874 TI - The use of biotic and abiotic components of Red Sea coastal areas as indicators of ecosystem health. AB - A biomonitoring study was conducted using some biotic (Pomadasys hasta and Lutjanus russellii fish) and abiotic (water and sediment) components of the Red Sea coast of Hodeida, Yemen Republic along two polluted sites (Al-Dawar beach and Urj village) in comparison to a reference site (Al-Nukhailah beach). The studied fish biomarkers included hepatosomatic index (HSI), condition factor (K), scaled mass index (SMI), catalase, glutathione-S-transferase (GST), malondialdehyde (MDA), total protein and albumin. In addition, metals (Fe, Cu, Zn, Pb and Cd) concentrations in water and sediment were measured and sediment pollution assessment was carried out using contamination factor (CF), geoaccumulation index (Igeo), pollution load index (PLI) and enrichment factor (EF). The studied metals concentration in water and sediment samples showed significant increase among the polluted sites in comparison to the reference site. Sediment pollution assessment generally confirmed that Urj village was the most contaminated site followed by Al-Dawar beach. Catalase, GST and MDA proved to be the most responsive biomarkers with increased values of GST and MDA at sites influenced by agricultural, urban and industrial activities while catalase, HSI, K, SMI, total protein and albumin showed the opposite trend. This study recommends monitoring of sediment Igeo and EF values as well as SMI, catalase, GST and MDA as sensitive indicators of different anthropogenic activities and their effects on aquatic ecosystems under complex and different gradients of metal pollution. In addition, P. hasta proved to be more sensitive towards the detected pollution condition. PMID- 26547875 TI - A TME study with the fungicide pyrimethanil combined with different moisture regimes: effects on enchytraeids. AB - Today's ecosystems are influenced by different factors that could evolve into stressors. Effects of pesticides, especially in agricultural areas, may interact with environmental factors, such as soil moisture fluctuation caused by global climate change. In this contribution, two semi-field studies conducted in Germany and Portugal with terrestrial model ecosystems are presented. Their aim was to assess the effects of the fungicide pyrimethanil under different soil moisture levels on Enchytraeidae. In Portugal a no observed effect concentration design was chosen, using two concentration levels: the maximum application rate (MAR) according to the safe use registration within the European Union and five times the MAR (1.82 and 9.09 mg/kg dry soil, respectively). Both concentrations did neither affect the total enchytraeid abundance nor single populations. In Germany an ECx design (effect concentration) was conducted, using 11 concentrations. In general, 14 EC50 values for different combinations of single species, moisture level and sampling date were determined. The strongest effects were found in dry soil, particularly for Fridericia connata (EC50: 3.48 mg/kg dry soil after 8 weeks of exposure). The advantages and challenges of these test designs are discussed with regard to the registration process of pesticides in the European Union. In any case, enchytraeids are suitable test organisms in such higher tier studies for the combined evaluation of chemical and climatic stressors due to their usually high diversity and abundances and their close contact with the soil solution. PMID- 26547876 TI - Role of transpiration and metabolism in translocation and accumulation of cadmium in tobacco plants (Nicotiana tabacum L.). AB - Tobacco plants grown in pots and in hydroponic culture accumulated cadmium (Cd) particularly: the Cd content of tobacco leaves exceeded 100 mg/kg and the enrichment factor (the ratio of Cd in leaves to that in soil) was more than 4. These high levels of accumulation identify tobacco as a hyperaccumulator of Cd. Two transpiration inhibitors (paraffin or CaCl2) and shade decreased the Cd content of tobacco leaves, and the decrease showed a linear relationship with the leaf transpiration rate. A metabolism inhibitor, namely 2,4-dinitrophenol (DNP), and low temperature (4 degrees C) also lowered the Cd content of tobacco leaves, but the inhibitory effect of low temperature was greater. In the half number of leaves that were shaded, the Cd content decreased to 26.5% of that in leaves that were not shaded in the same tobacco plants. These results suggests that translocation of Cd from the medium to the leaves is driven by the symplastic and the apoplastic pathways. Probably, of the two crucial steps in the translocation of Cd in tobacco plants, one, namely uptake from the medium to the xylem, is energy-dependent whereas the other, namely the transfer from the xylem to the leaves, is driven mainly by transpiration. PMID- 26547877 TI - New insights into the risk of phthalates: Inhibition of UDP glucuronosyltransferases. AB - Wide utilization of phthalates-containing products results in the significant exposure of humans to these compounds. Many adverse effects of phthalates have been documented in rodent models, but their effects in humans exposed to these chemicals remain unclear until more mechanistic studies on phthalate toxicities can be carried out. To provide new insights to predict the potential adverse effects of phthalates in humans, the recent study investigated the inhibition of representative phthalates di-n-octyl ortho-phthalate (DNOP) and diphenyl phthalate (DPhP) towards the important xenobiotic and endobiotic-metabolizing UDP glucuronosyltransferases (UGTs). An in vitro UGTs incubation system was employed to study the inhibition of DNOP and DPhP towards UGT isoforms. DPhP and DNOP weakly inhibited the activities of UGT1A1, UGT1A7, and UGT1A8. 100 uM of DNOP inhibited the activities of UGT1A3, UGT1A9, and UGT2B7 by 41.8% (p < 0.01), 45.6% (p < 0.01), and 48.8% (p < 0.01), respectively. 100 uM of DPhP inhibited the activity of UGT1A3, UGT1A6, and UGT1A9 by 81.8 (p < 0.001), 49.1% (p < 0.05), and 76.4% (p < 0.001), respectively. In silico analysis was used to explain the stronger inhibition of DPhP than DNOP towards UGT1A3 activity. Kinetics studies were carried our to determine mechanism of inhibition of UGT1A3 by DPhP. Both Dixon and Lineweaver-Burk plots showed the competitive inhibition of DPhP towards UGT1A3. The inhibition kinetic parameter (Ki) was calculated to be 0.89 uM. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1>[I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), these studies predicted in vivo drug drug interaction might occur when the plasma concentration of DPhP was above 0.089 uM. Taken together, this study reveales the potential for adverse effects of phthalates DNOP and DPhP as a result of UGT inhibition. PMID- 26547878 TI - Cu and Zn adsorption to a heterogeneous natural sediment: Influence of leached cations and natural organic matter. AB - Adsorption of heavy metals by natural sediments has important implications to the fate and transport of contaminants in subsurface environments. Although the importance of major multivalent cations and dissolved organic matter (DOM) in heavy metal adsorption had been previously demonstrated, the leaching of major cations and DOM from sediments and its influence on heavy metal adsorption have not been fully examined. In this study, the concentrations of Ca, Mg, Al, Fe, and natural organic matter that leached from a natural sediment in Cu and Zn adsorption experiments were measured and used in surface complexation models to elucidate their effects on Cu and Zn adsorption. Experimental results showed that the leaching of cations and DOM was substantial and pH-dependent. The leached concentrations of Ca and Mg were reasonably simulated based on BaCl2 extractable Ca and Mg at pH < 5, and Al and Fe activities were accurately predicted for specific pH ranges by assuming solubility control by Al(OH)3 and Fe(OH)3. Visual MINTEQ simulations showed that the leached cations markedly decreased Cu adsorption at pH < 6 and Zn adsorption at pH 3-8. Due to varying affinity for DOM between Cu and Zn, DOM was found to decrease Cu adsorption at pH > 6 due to formation of Cu-DOM aqueous complexes, but increase Zn adsorption at pH 4-7 due to formation of aqueous complexes between DOM and major cations, which reduced competition from these cations against Zn for binding sites on the sediment. PMID- 26547879 TI - Assessment of metal concentrations in indigenous and caged mussels (Mytilus galloprovincialis) on entire Turkish coastline. AB - This survey was conducted to determine metal concentrations in the biomonitor organism Mytilus galloprovincialis collected from all coasts of Turkey. Naturally occurring mussels were gathered along the coast of the Black Sea, Sea of Marmara, Bosphorus and Aegean Sea, while a 6-month transplantation session was implemented on the Levantine Sea coast where M. galloprovincialis does not adapt naturally. Mussels collected from the Izmir area were employed for transplantation to five locations along the Levantine Sea coast of Turkey. Concentrations of Ag, Al, As, Cd, Co, Cr, Cu, Fe, K, Mn, Ni, Pb, Sn, V, and Zn were measured using ICP-MS (Inductively Coupled Plasma-Mass Spectrometry). Results showed that concentrations of some essential elements (Co, Fe, K, Mn, Zn) generally fell within the range of acceptable global values. However, at some sampling sites the metal concentrations were found at higher levels compared to the world average and recommended limits. For instance, very high Ag and Cu concentrations were observed in mussel caged at Yumurtalik. Elevated As, Ni, Pb, and V concentrations were observed at the Tirebolu, Eregli, Eskihisar, and Tekirdag locations, respectively. Taking into account all measured metals, it can be inferred that Yumurtalik is the most metal-contaminated locality. The results highlighted metal specific pollution at coastal areas in each sea cover Turkey. In spite of the high metal levels estimated daily intakes (EDI) of the measured elements were well below through very low mussel consumption by Turkish public. PMID- 26547880 TI - Impact of anionic ion exchange resins on NOM fractions: Effect on N-DBPs and C DBPs precursors. AB - The formation potential of carbonaceous and nitrogenous disinfection by-products (C-DBPs, N-DBPs) after ion exchange treatment (IEX) of three different water types in multiple consecutive loading cycles was investigated. Liquid chromatography with organic carbon detector (LC-OCD) was employed to gauge the impact of IEX on different natural organic matter (NOM) fractions and data obtained were used to correlate these changes to DBPs Formation Potential (FP) under chlorination. Humic (-like) substances fractions of NOM were mainly targeted by ion exchange resins (40-67% removal), whereas hydrophilic, non-ionic fractions such as neutrals and building blocks were poorly removed during the treatment (12-33% removal). Application of ion exchange resins removed 13-20% of total carbonaceous DBPs FP and 3-50% of total nitrogenous DBPs FP. Effect of the inorganic nitrogen (i.e., Nitrate) presence on N-DBPs FP was insignificant while the presence of dissolved organic nitrogen (DON) was found to be a key parameter affecting the formation of N-DBPs. DON especially the portion affiliated with humic substances fraction, was reduced effectively (~77%) as a result of IEX treatment. PMID- 26547881 TI - Motor dysfunction within the schizophrenia-spectrum: A dimensional step towards an underappreciated domain. AB - At the beginning of the 20th century, genuine motor abnormalities (GMA) were considered to be intricately linked to schizophrenia. Subsequently, however, GMA have been increasingly regarded as unspecific transdiagnostic phenomena or related to side effects of antipsychotic treatment. Despite possible medication confounds, within the schizophrenia spectrum GMA have been categorized into three broad categories, i.e. neurological soft signs, abnormal involuntary movements and catatonia. Schizophrenia patients show a substantial overlap across a broad range of distinct motor signs and symptoms suggesting a prominent involvement of the motor system in disease pathophysiology. There have been several attempts to increase reliability and validity in diagnosing schizophrenia based on behavior and neurobiology, yet relatively little attention has been paid to the motor domain in the past. Nevertheless, accumulating neuroscientific evidence suggests the possibility of a motor endophenotype in schizophrenia, and that GMA could represent a specific dimension within the schizophrenia-spectrum. Here, we review current neuroimaging research on GMA in schizophrenia with an emphasis on distinct and common mechanisms of brain dysfunction. Based on a dimensional approach we show that multimodal neuroimaging combined with fine-grained clinical examination can result in a comprehensive characterization of structural and functional brain changes that are presumed to underlie core GMA in schizophrenia. We discuss the possibility of a distinct motor domain, together with its implications for future research. Investigating GMA by means of multimodal neuroimaging can essentially contribute at identifying novel and biologically reliable phenotypes in psychiatry. PMID- 26547882 TI - Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia. PMID- 26547883 TI - Caring for dying cancer patients in the Chinese cultural context: A qualitative study from the perspectives of physicians and nurses. AB - OBJECTIVE: To explore the experiences of Chinese physicians and nurses who care for dying cancer patients in their practical work. METHOD: This was a qualitative study using semi-structured face-to-face interviews. Fifteen physicians and 22 nurses were recruited from a cancer center in mainland China. The data were analyzed by qualitative thematic analysis. RESULTS: Disclosure of information on death and cancer to dying cancer patients is taboo in traditional Chinese culture, which greatly decreases the physicians' and nurses' effective communication with dying patients in end-of-life (EOL) care. Both physicians and nurses described strong ambitions to give dying cancer patients high-quality care, and they emphasized the importance of maintaining dying patients' hopes in the death-denying cultural context. However, the nurses were more concerned with dying patients' physical comfort and wish fulfillment, while the physicians placed greatest emphasis on patients' rights and symptom management. Both physicians and nurses suffered whilst also benefitting from taking care of dying patients which helped with their personal growth and allowed greater insight into themselves and their clinical practice. Our results also indicated that Chinese physicians and nurses require improved methods of communication on EOL care, as well as needing more support to provide quality EOL care. CONCLUSION: Chinese physicians and nurses experience a challenge when caring for dying cancer patients in the Chinese cultural context. Flexible and specific education and training in EOL cancer care are required to meet the needs of Chinese physicians and nurses at the cancer center studied. PMID- 26547884 TI - Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay. AB - Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test. Our aim was to identify both known and novel specific ANA in dogs and to investigate if different IIF-ANA patterns are associated with different specific ANA in dogs. Sera from 240 dogs with suspicion of autoimmune disease (210 IIF-ANA positive (ANA(pos)) and 30 IIF-ANA negative (ANA(neg))) as well as sera from 27 healthy controls were included. The samples were analysed with a line immunoassay, LIA (Euroline ANA Profile 5, Euroimmun, Lubeck, Germany) and four different ELISAs (Euroimmun). The ANA(pos) dogs were divided in two groups depending on the type of IIF-ANA pattern. Of the 210 ANA(pos) samples 68 were classified as ANA homogenous (ANA(H)) and 141 as ANA speckled (ANA(S)), one sample was not possible to classify. Dogs in the ANA(H) group had, compared to the other groups, most frequently high levels of anti double stranded deoxyribonucleic acid (dsDNA) and anti-nucleosome ANA. Anti-dsDNA antibodies were confirmed in some dogs with the Crithidia luciliae indirect immunofluorescence test (CLIFT). The frequency of ANA(H) dogs with values above those observed in the healthy group was significantly higher compared to ANA(S) dogs for anti-dsDNA, anti-nucleosome, and anti-histone reactivity. Dogs in the ANA(S) group had, compared to the other groups, most frequently high levels of anti-ribonucleoproteins (RNP) and/or anti-Smith (Sm) antibodies. Reactivity against Sjogren's syndrome related antigens (SS)-A (including the Ro-60 and Ro-52 subcomponents), SS-B, histidyl tRNA synthetase (Jo-1), topoisomerase I antigen (Scl-70), polymyositis-scleroderma antigen (PM-Scl) and proliferating cell nuclear antigen (PCNA) was also noted in individual dogs. In conclusion, by using a commercial LIA and different ELISAs originally developed for detection of human ANA, we identified several specific ANA in serum samples from dogs sampled for IIF-ANA testing. Further, we found that the types of IIF-ANA pattern were associated with reactivity against some particular nuclear antigens. PMID- 26547885 TI - Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation. AB - The immunomodulatory properties of gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25MUg/mL LPS, the levels of TNF-alpha, IL-1beta and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-alpha and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus. PMID- 26547886 TI - When does social learning become cultural learning? AB - Developmental research on selective social learning, or 'social learning strategies', is currently a rich source of information about when children copy behaviour, and who they prefer to copy. It also has the potential to tell us when and how human social learning becomes cultural learning; i.e. mediated by psychological mechanisms that are specialized, genetically or culturally, to promote cultural inheritance. However, this review article argues that, to realize its potential, research on the development of selective social learning needs more clearly to distinguish functional from mechanistic explanation; to achieve integration with research on attention and learning in adult humans and 'dumb' animals; and to recognize that psychological mechanisms can be specialized, not only by genetic evolution, but also by associative learning and cultural evolution. PMID- 26547887 TI - Clinical study of 20 patients with incontinentia pigmenti. AB - BACKGROUND: Incontinentia pigmenti (IP) is a rare genodermatosis with early prenatal lethality in affected males. Clinical manifestations are usually more exuberant in sporadic than in familial cases. Cutaneous manifestations occur in all sporadic cases and about 96% of familial cases. As well as the skin, other tissues arising from the neuroectoderm may be affected. OBJECTIVES: This study was designed to evaluate dermatologic, dental, neurologic, and ophthalmologic manifestations in patients with IP. METHODS: Findings in IP patients and family members also diagnosed with IP in Porto Alegre, Brazil, during 2003-2012, were analyzed. RESULTS: Thirteen children and seven relatives were diagnosed with IP; 38.4% of cases were familial, and 61.5% were sporadic. Mean +/- standard deviation follow-up was 46.08 +/- 39.47 months. Frequencies of 100% and 85.7% for dermatologic manifestations, 23.0% and 0% for neurologic manifestations, 62.5% and 71.4% for dental manifestations, and 11.1% and 42.8% for ophthalmologic manifestations were found in affected children and relatives, respectively. Associated diseases include Wilms' tumor, myasthenia gravis, Still's syndrome, and congenital hypothyroidism. CONCLUSIONS: These findings reinforce the heterogeneity of dermatologic findings and the numerous extracutaneous manifestations requiring a multidisciplinary approach. The follow-up of patients with IP is important in the detection of serious associated diseases. The relationships between these disorders and IP raise the need for additional longitudinal studies with longterm monitoring of these patients. The management of IP in clinical practice may benefit from early efforts to detect associated diseases. PMID- 26547888 TI - Perianal pyoderma gangrenosum after excision and fulguration of anal condyloma acuminatum. AB - INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, inflammatory skin pathology frequently associated with systemic inflammatory disease. While rare after surgery, recognition of this disease in the post-surgical setting is important as it can mimic wound infection. PRESENTATION OF CASE: We herein present a dramatic presentation of perianal PG four days after routine excision and fulguration of anal condyloma acuminatum. The affected area did not improve with broad spectrum antibiotics or surgical debridement. A diagnosis of PG was made from clinical suspicion and pathology findings, and further confirmed with rapid improvement after starting steroids. Diagnosis of this disease in the postoperative period requires high suspicion when the characteristic ulcerative or bullae lesions are seen diffusely and show minimal improvement with antibiotic treatment or debridement. DISCUSSION: Our case highlights the importance of recognizing this disease in the post-operative period, to allow for early initiation of appropriate treatment and prevent unnecessary surgical debridement of a highly sensitive area. There have been 32 case reports of PG in the colorectal literature, mostly following stoma creation. There is one case report of idiopathic perianal pyoderma gangrenosum with no known prior trauma. To our knowledge there are no previously reported cases of perianal PG after routine elective anorectal surgery. CONCLUSION: This is the first reported case of perianal pyoderma gangrenosum in the post-surgical setting. Increased awareness of pyoderma gangrenosum in the surgical literature will aid in prompt diagnosis and proper medical management of this uncommon postoperative morbidity. PMID- 26547889 TI - A modular informatics platform for effective support of collaborative and multicenter studies in cardiology. AB - Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease. PMID- 26547890 TI - Multicenter clinical trial of high-intensity focused ultrasound treatment in glaucoma patients without previous filtering surgery. AB - PURPOSE: To evaluate the efficacy and safety of the ultrasonic circular cyclocoagulation procedure in patients with open-angle glaucoma naive of previous filtering surgery. METHODS: Prospective non-comparative interventional clinical study conducted in five French University Hospitals. Thirty eyes of 30 patients with open-angle glaucoma, intra-ocular pressure (IOP) > 21 mmHg and with no previous filtering glaucoma surgeries were sonicated with a probe comprising six piezoelectric transducers. The six transducers were activated with a 6-s exposure time. Complete ophthalmic examinations were performed before the procedure and at 1 day, 1 week, 1, 2, 3, 6 and 12 months after the procedure. Primary outcomes were qualified surgical success (defined as IOP reduction from baseline >=20% and IOP > 5 mmHg with possible re-intervention and without hypotensive medication adjunction) and complete surgical success (defined as IOP reduction from baseline >=20%, IOP > 5 mmHg and IOP < 21 mmHg with possible re-intervention and without hypotensive medication adjunction) at the last follow-up visit and vision threatening complications. Secondary outcomes were mean IOP at each follow-up visit compared with baseline, medication use, complications and re-interventions. RESULTS: Intra-ocular pressure was significantly reduced (p < 0.05) from a mean pre-operative value of 28.2 +/- 7.2 mmHg (n = 3.6 hypotensive medications) to 19.6 +/- 7.9 mmHg at 12 months (n = 3.1 hypotensive medications and n = 1.1 procedures) (mean IOP reduction of 30%). Qualified success was achieved in 63% of eyes (19/30) (mean IOP reduction of 37% in these eyes) and complete success in 46.7% of eyes (14/30) (mean IOP reduction of 37% in these eyes) at the last follow-up. No major intra- or post-operative complications occurred. CONCLUSIONS: The UC(3) procedure seems to be an effective and well-tolerated method to reduce IOP in patients with open-angle glaucoma without previous filtering surgery. PMID- 26547891 TI - [Common benign breast tumors including fibroadenoma, phyllodes tumors, and papillary lesions: Guidelines]. AB - OBJECTIVES: To provide guidelines for clinical practice from the French College of Obstetrics and Gynecology (CNGOF), based on the best evidence available, concerning common benign breast tumors: fibroadenoma (FA), phyllodes breast tumors (PBT), and papillary lesions (BPL). METHODS: Bibliographical search in French and English languages by consultation of PubMed, Cochrane and international databases. RESULTS: In case of percutaneous biopsy diagnosis of FA, clinico-radiologic and pathologic discordance or complex FA or proliferative lesions or atypia with FA, a family history of cancer, it seems legitimate to discuss management in a multidisciplinary meeting. When surgery is proposed for FA, periareolar compared to direct incision is associated with more insensitive nipple but better aesthetic results (LE4). When surgery is proposed for FA, indirect incision is preferable for better cosmetic results (Grade C). Techniques of percutaneous destruction or resection can be used (Grade C). The WHO classification distinguishes three categories of phyllodes tumors (PBT): benign (grade 1), borderline (grade 2) and malignant (grade 3). For grade 1 PBT, the risk of local recurrence after surgical excision increases when PBT lesion is in contact with surgical limits (not in sano). After in sano resection, there is no correlation between margin size and the risk of recurrence (LE4). For grade 2 PBT, local recurrence after surgical excision increases for margins under 10mm margins (LE4). For grade 1-2 PBT, in sano excision is recommended. For grade 2 PBT, 10-mm margins are recommended (Grade C). No lymph node evaluation or neither systematic mastectomy is recommended (Grade C). Breast papillary lesion (BPL) without atypia, complete resection of radiologic signal is recommended (Grade C). For BPL with atypia, complete excisional surgery is recommended (Grade C). PMID- 26547892 TI - Use of dermoscopy to identify nail plate cavities as a clinical diagnostic clue for onychomatricoma. PMID- 26547894 TI - Federal Funding for Food Science--Challenges and Opportunities. PMID- 26547896 TI - A Statistical Error in: "Analysis of Caecal Microbiota in Rats Fed with Genetically Modified Rice by Real-Time Quantitative PCR". PMID- 26547897 TI - Response to Panchin's Letter on Statistics. PMID- 26547898 TI - Contrasting patterns of selection and drift between two categories of immune genes in prairie-chickens. AB - Immune-receptor genes of the adaptive immune system, such as the major histocompatibility complex (MHC), are involved in recognizing specific pathogens and are known to have high rates of adaptive evolution, presumably as a consequence of rapid co-evolution between hosts and pathogens. In contrast, many 'mediating' genes of the immune system do not interact directly with specific pathogens and are involved in signalling (e.g. cytokines) or controlling immune cell growth. As a consequence, we might expect stronger selection at immune receptor than mediating genes, but these two types of genes have not been compared directly in wild populations. Here, we tested the hypothesis that selection differs between MHC (class I and II) and mediating genes by comparing levels of population differentiation across the range of greater prairie-chickens (Tympanuchus cupido). As predicted, there was stronger population differentiation and isolation by distance at immune receptor (MHC) than at either mediating genes or neutral microsatellites, suggesting a stronger role of local adaptation at the MHC. In contrast, mediating genes displayed weaker differentiation between populations than neutral microsatellites, consistent with selection favouring similar alleles across populations for mediating genes. In addition to selection, drift also had a stronger effect on immune receptor (MHC) than mediating genes as indicated by the stronger decline of MHC variation in relation to population size. This is the first study in the wild to show that the effects of selection and drift on immune genes vary across populations depending on their functional role. PMID- 26547899 TI - A Call for Change in the Diagnosis and Treatment of Patients with Ductal Carcinoma In Situ: An Opportunity to Minimize Overdiagnosis and Overtreatment. PMID- 26547900 TI - Triple-Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience. AB - Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non-amplification of human epidermal growth factor receptor-2 (HER2)/neu are termed triple-negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti-HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non-TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology-based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age-specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non-TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry. PMID- 26547901 TI - "Targeting or supporting, what drives patterns of aggressive intervention in fights?". AB - GrooFiWorld is an individual-based, computational model of social interactions that can be used to examine factors underlying reciprocation and interchange of social behavior in primate societies. Individuals within GrooFiWorld are programed to maintain spatial proximity and thereby form a group. When an individual encounters another individual in its proximity, the individual attacks the other if the risk of losing is low. Otherwise, the individual considers grooming the other. Patterns of social behavior that emerge in the model resemble empirical data from primates. Triadic aggression emerges when an individual attacks one of the former combatants by chance immediately after an aggressive interaction, and reciprocation and interchange of grooming and support emerge even though individuals have no intention to help others or pay back services. The model generates predictions for patterns of contra-intervention that are counterintuitive within a framework of interchange of social services, such as that individuals receive more contra-intervention from those whom they groom more frequently. Here we tested these predictions in data collected on social interactions in a group of bonnet macaques (Macaca radiata). We confirmed the predictions of the model in the sense that contra-intervention was strongly correlated with dyadic aggression which suggests that contra-intervention is a subset of dyadic aggression. Adult females directed more contra-intervention to those individuals from whom they received more grooming. Further, contra intervention was directed down the dominance hierarchy such that adult females received more contra-intervention from higher ranking females. Because these findings are consistent with the predictions from the GrooFiWorld model, they suggest that the distribution of interventions in fights is regulated by factors such as dominance rank and spatial structure rather than a motivation to help others and interchange social services. PMID- 26547903 TI - Corrigendum. PMID- 26547902 TI - Couples Relationship Education and Couples Therapy: Healthy Marriage or Strange Bedfellows? AB - This paper focuses on issues sparked by the Couples Relationship Education (CRE) field moving toward a more clinical model to meet the needs of an increasing number of distressed couples coming to CRE programs. We review the concerns raised and recommendations made by Bradford, Hawkins, and Acker (2015), most of which push CRE toward a more clinical model. We address these recommendations and make suggestions for best practices that preserve the prevention/education model underlying research-based CRE. The three main issues are couple screening, leader training, and service delivery models. Our suggested best practices include: conducting minimal screening including the assessment of dangerous levels of couple violence, training leaders with key skills to handle issues raised by distressed couples as well as other couples who may place additional burdens on leaders, providing referrals and choices of programs available to participants at intake and throughout the CRE program, and adding (rather than integrating) clinical services to CRE services for couples who desire additional intervention. Finally, throughout the paper, we review other key issues in the CRE field and make recommendations made for future research and practice. PMID- 26547904 TI - Stanniocalcin1 gene expression in patients with acute leukemia: impact on response to therapy and disease outcome. AB - INTRODUCTION: Stanniocalcin1 (STC1) is a hormone that regulates cell growth and survival; this study aimed to evaluate the STC1 gene expression in patients with acute leukemia and assess its prognostic significance. METHODS: Seventy-six patients with acute leukemia were enrolled for determination of mRNA STC1 by real time quantitative polymerase chain reaction at diagnosis and at day 28. RESULTS: Median STC1 gene expression was 16.2 and 4.43 in patients with acute myeloid leukemia and 9.67 and 2.37 in patients with acute lymphoblastic leukemia on days 0 and 28, respectively. A cutoff level for STC1 gene expression was established subdividing patients into high- and low-STC1 gene expression groups. Median STC1 gene expression at days 0 and 28 was significantly higher among patients who were nonresponders to therapy than among those who were therapy responders in both groups. Patients achieving complete remission had significantly lower baseline STC1 gene expression than those in relapse. High STC1 gene expression was associated with shorter overall and disease-free survival times. CONCLUSION: STC1 gene expression at diagnosis might be a useful prognostic marker for clinical outcome and monitoring therapeutic response in patients with acute leukemia. PMID- 26547905 TI - Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital. AB - WHAT IS KNOWN AND OBJECTIVE: Clostridium difficile infection (CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. METHODS: Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post implementation. RESULTS AND DISCUSSION: One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48.1%) post implementation (P = 0.01). The median time to treatment with vancomycin was reduced from five days to one day (P < 0.01), with median length of hospital stay decreasing from 30 days to 21 days (P = 0.01) post-implementation. There was no difference in 30-day all-cause mortality. WHAT IS NEW AND CONCLUSION: A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity. PMID- 26547906 TI - Expression of inflammatory cytokines and MMPs on replanted teeth at different extra-alveolar time: an ex vivo and in vivo study. AB - BACKGROUND: Immediately after the avulsed tooth is replanted, a complex inflammatory response ensues. As part of the periodontium healing process, the extracellular matrix macromolecules are essential to create the cellular environment required during healing and morphogenesis. AIM: This study was designed to evaluate the correlation between different extra-alveolar dry times and inflammatory cytokines and matrix metalloproteinases (MMPs) as part of the periodontal ligament (PDL) gene expression. DESIGN: The first phase of the study aimed testing human PDL cells ex vivo. Extracted teeth were dried for 15 and 30 min. The PDL cells were extracted and analyzed by qRT-PCR. The second phase was performed in vivo, and 36 Sprague Dawley rat first maxillary molars were extracted and replanted after 15, 30, and 60 min extra-alveolar time. We tested the levels of inflammatory cytokines and MMPS in periodontal tissue at 3, 7, and 28 days after tooth replantation. The replanted area was dissected, grounded, and analyzed by RT-PCR. RESULTS: Expressions of IL-1beta, IL-6, TNF-alpha, and MMP-3 and MMP-9 were significantly higher in the replanted teeth. Extended dry time had a direct correlation with induction of pro-inflammatory cytokine and MMPs in PDL cells. CONCLUSION: Our study showed that pro-inflammatory cytokines were more significantly expressed in the tissues surrounding the replanted teeth. Future research must be undertaken to additionally confirm the release of these cytokines and be focused on the inhibition of these cytokines to reduce inflammation of replanted teeth. PMID- 26547907 TI - Sensemaking and the co-production of safety: a qualitative study of primary medical care patients. AB - This study explores the ways in which patients make sense of 'safety' in the context of primary medical care. Drawing on qualitative interviews with primary care patients, we reveal patients' conceptualisation of safety as fluid, contingent, multi-dimensional, and negotiated. Participant accounts drew attention to a largely invisible and inaccessible (but taken for granted) architecture of safety, the importance of psycho-social as well as physical dimensions and the interactions between them, informal strategies for negotiating safety, and the moral dimension of safety. Participants reported being proactive in taking action to protect themselves from potential harm. The somewhat routinised and predictable nature of the primary medical care consultation, which is very different from 'one off' inpatient spells, meant that patients were not passive recipients of care. Instead they had a stock of accumulated knowledge and experience to inform their actions. In addition to highlighting the differences and similarities between hospital and primary care settings, the study suggests that a broad conceptualisation of patient safety is required, which encompasses the safety concerns of patients in primary care settings. PMID- 26547908 TI - Pathways of healthcare utilisation in patients with suspected adolescent idiopathic scoliosis: a cross-sectional study. AB - BACKGROUND: School screening programs for adolescent idiopathic scoliosis (AIS) have been discontinued in Canada and elsewhere because they were not considered cost-effective. In communities lacking such programs, we expect a significant variety of healthcare pathways and timeframes for patient referrals to orthopaedics. The objectives of this study were: 1) to characterise the healthcare pathways of young children with suspected AIS in a population without school screening; and 2) to investigate the relationships between these healthcare pathways and the appropriateness of referrals to specialised orthopaedic clinics. METHODS: This study concerned all children, ages 10 to 18, referred for an initial visit for suspected AIS to any of the five out-patient paediatric orthopaedic clinics of south-western Quebec (Canada). For the 831 participants, referrals to orthopaedics were characterised as appropriate, late, or inappropriate, based on known risk factors for AIS progression and on treatment indications. Parents documented the circumstances of healthcare use prior to the orthopaedic consultation. Relevant predisposing, enabling, and need variables derived from Andersen's Behavioral Model of Health Services Use were also documented. Healthcare pathways were characterised by developing a taxonomy using multiple correspondence analysis prior to hierarchical classification. Associations between the healthcare pathways and appropriateness of referral were assessed using multinomial regression analyses. RESULTS: We constructed a taxonomy of five distinct healthcare pathways: 1) Lay/regular source of care interrelation, 2) Other professionals, 3) Lay/consultation discontinuity, 4) Other medical doctor, and 5) Regular source of care continuity. Laypersons played an important role in AIS suspicion (53% of cases), but did not prevent late referrals. Continuity of care, as opposed to numerous uncoordinated consultations, was an effective strategy to prevent late referrals (OR = 0.32 [0.17-0.59]), but was related to increased probability of inappropriate referrals. CONCLUSIONS: We identified two cardinal characteristics that distinguished the healthcare pathways and related significantly to appropriateness of referral status, namely the role of laypersons and the involvement of the regular source of care. This suggests directions for intervention such as advocating for access to a regular source of care, increasing awareness of the disease to medical practitioners' and improving their knowledge of AIS detection and referral criteria. PMID- 26547909 TI - Return-to-Work Within a Complex and Dynamic Organizational Work Disability System. AB - Background Return-to-work (RTW) within a complex organizational system can be associated with suboptimal outcomes. Purpose To apply a sociotechnical systems perspective to investigate complexity in RTW; to utilize system dynamics modeling (SDM) to examine how feedback relationships between individual, psychosocial, and organizational factors make up the work disability system and influence RTW. Methods SDMs were developed within two companies. Thirty stakeholders including senior managers, and frontline supervisors and workers participated in model building sessions. Participants were asked questions that elicited information about the structure of the work disability system and were translated into feedback loops. To parameterize the model, participants were asked to estimate the shape and magnitude of the relationship between key model components. Data from published literature were also accessed to supplement participant estimates. Data were entered into a model created in the software program Vensim. Simulations were conducted to examine how financial incentives and light duty work disability-related policies, utilized by the participating companies, influenced RTW likelihood and preparedness. Results The SDMs were multidimensional, including individual attitudinal characteristics, health factors, and organizational components. Among the causal pathways uncovered, psychosocial components including workplace social support, supervisor and co worker pressure, and supervisor-frontline worker communication impacted RTW likelihood and preparedness. Interestingly, SDM simulations showed that work disability-related policies in both companies resulted in a diminishing or opposing impact on RTW preparedness and likelihood. Conclusion SDM provides a novel systems view of RTW. Policy and psychosocial component relationships within the system have important implications for RTW, and may contribute to unanticipated outcomes. PMID- 26547910 TI - Concentrations of Mineral in Amniotic Fluid and Their Relations to Selected Maternal and Fetal Parameters. AB - The concentrations of various trace elements in amniotic fluid (AF) change over the course of pregnancy, with gestational age and fetus growth. The aim of the present study was to evaluate the concentrations of selected essential and toxic elements in AF and their relations to maternal and fetal parameters. The study was carried out in 39 pregnant women, aged 34.6 +/- 4.7 years, between weeks 16 and 26 of gestation. Amniotic fluid samples were obtained during the standard procedure of amniocentesis in high-risk patients for chromosomal abnormalities. An inductively coupled plasma mass spectrometry (ICP-MS) technique was used to determine the levels of Al, As, Ba, Cd, Co, Cr, Cu, Mg, Mn, Ni, Sr, U, and V in AF. Body mass and blood pressure were measured in all the women. The basic parameters of fetal development were also assayed. It was found that the age of the mother, the gender of the fetus, and the week of the pregnancy may affect the concentrations of mineral in the amniotic fluid. Moreover, several significant correlations between the essential and toxic elements and maternal and fetal parameters were observed. In particular, negative and positive correlations between fetal parameters and magnesium and copper levels in AF, respectively, were seen. The present findings demonstrate the association between minerals in AF and fetal development. PMID- 26547911 TI - Seizure reduction is a prognostic marker in low-grade glioma patients treated with temozolomide. AB - We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a >=50 % seizure reduction and MRI response 6, 12 and 18 months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95 % CI 0.19-0.73; p = 0.004) and OS (HR 0.39; 95 % CI 0.18 0.85; p = 0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95 % CI 62.0-112.9) than patients without a response (median 34.4mo; 95 % CI 26.1-42.6; p = 0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response. PMID- 26547913 TI - A Qualitative Study of Vulnerable Patient Views of Type 2 Diabetes Consumer Reports. AB - BACKGROUND: The Patient Protection and Affordable Care Act (ACA) mandates the release of publicly available consumer reports to highlight differences in quality of care and reduce healthcare disparities. However, little is known about patient perceptions of the value of such reports. OBJECTIVE: This study aims to identify whether vulnerable populations with type 2 diabetes perceive consumer reports as helpful in making decisions about diabetes care. METHODS: We conducted a brief demographic survey and qualitative study of 18 focus groups: six each of African American, Hispanic, and non-Hispanic White consumers diagnosed with type 2 diabetes (n = 92). We analysed focus group transcripts to identify recurring themes, which were summarized and compared across population groups. RESULTS: Participants expressed minimal interest in currently available consumer reports. They instead listed personal referrals and interpersonal interactions among the most important factors when choosing a physician. Further, in place of information to aid in physician selection, participants articulated strong desires for more basic, straightforward disease-specific information that would promote diabetes self-management. CONCLUSIONS: This study's results call into question the value of consumer reports as defined by the ACA. Participants reported little interest in comparative provider performance data. Instead, they were more interested in information to assist in diabetes self-management. This suggests that consumer reports may not be as important a tool to improve outcomes and reduce health disparities as policy makers imagine them to be. PMID- 26547912 TI - A Systematic Review of Factors Associated with Non-Adherence to Treatment for Immune-Mediated Inflammatory Diseases. AB - BACKGROUND: Non-adherence impacts negatively on patient health outcomes and has associated economic costs. Understanding drivers of treatment adherence in immune mediated inflammatory diseases is key for the development of effective strategies to tackle non-adherence. OBJECTIVE: To identify factors associated with treatment non-adherence across diseases in three clinical areas: rheumatology, gastroenterology, and dermatology. DESIGN: Systematic review. DATA SOURCES: Articles published in PubMed, Science Direct, PsychINFO and the Cochrane Library from January 1, 1980 to February 14, 2014. STUDY SELECTION: Studies were eligible if they included patients with a diagnosis of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, or psoriasis and included statistics to examine associations of factors with non-adherence. DATA EXTRACTION: Data were extracted by the first reviewer using a standardized 23 item form and verified by a second/third reviewer. Quality assessment was carried out for each study using a 16-item quality checklist. RESULTS: 73 studies were identified for inclusion in the review. Demographic or clinical factors were not consistently associated with non-adherence. Limited evidence was found for an association between non-adherence and treatment factors such as dosing frequency. Consistent associations with adherence were found for psychosocial factors, with the strongest evidence for the impact of the healthcare professional-patient relationship, perceptions of treatment concerns and depression, lower treatment self-efficacy and necessity beliefs, and practical barriers to treatment. CONCLUSIONS: While examined in only a minority of studies, the strongest evidence found for non-adherence were psychosocial factors. Interventions designed to address these factors may be most effective in tackling treatment non-adherence. PMID- 26547914 TI - Assessment of Transdermal Buprenorphine Patches for the Treatment of Chronic Pain in a UK Observational Study. AB - BACKGROUND: Opioids provide effective analgesia for moderate-to-severe, chronic pain. Transdermal buprenorphine (TDB) is available in the UK as weekly, lower dose (5-20 MUg/h) patches and twice-weekly, higher dose (35-70 MUg/h) patches. This prospective, observational, multicenter study of patients with various chronic pain conditions assessed the safety, perceptions, and discontinuation of treatment with TDB in a real-world, non-interventional setting (ClinicalTrials.gov study ID: NCT01225861). METHODS: Patients aged >=18 years who were already receiving or initiating treatment with TDB were recruited in the UK during routine clinical visits and were followed for 6 visits or 9 months (whichever came first). Self-reported treatment adherence, patient satisfaction, and safety data were collected at each study visit. RESULTS: Of 465 patients, 272 were already receiving 7-day TDB at the study start (TDB experienced), 146 were TDB naive, and 47 were prescribed twice-weekly TDB. Most patients were female (72.9 %) and overweight/obese (body mass index >=25: 75.3 %). The median age was 67 years, and the mean duration of pain was 11.1 years. Arthritis/other musculoskeletal disorders (39.6 %) were the most common causes of pain. Mild adverse events were commonly reported. Skin irritations, which were most frequent in 7-day TDB-experienced patients (45.6 %), rarely resulted in treatment discontinuation (8.8 %). Nearly all patients used TDB in accordance with treatment recommendations. Most patients reported that TDB was 'effective'/'very effective' at relieving pain and were 'satisfied'/'very satisfied' with TDB therapy. CONCLUSION: In everyday clinical practice, TDB was well tolerated and patients were satisfied with their therapy. Self-reported adherence to TDB was very high, and adverse events rarely resulted in treatment discontinuation. Opportunities were identified to limit common adverse events associated with TDB. PMID- 26547915 TI - Prognostic role of N-terminal pro-brain natriuretic peptide in asymptomatic hypertensive and diabetic patients in primary care: impact of age and gender : Results from the PROBE-HF study. AB - BACKGROUND: The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care. METHODS: NT proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 +/- 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 +/- 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction. RESULTS: Patients with NT-proBNP above the 80th age- and gender specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014). CONCLUSIONS: NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women. PMID- 26547917 TI - Evaluation of the safety and pathological effects of neoadjuvant full-dose gemcitabine combination radiation therapy in patients with biliary tract cancer. AB - PURPOSE: This study aimed to evaluate the safety of neoadjuvant gemcitabine combination radiation therapy in the treatment of biliary tract cancer and to investigate the pathological effects of chemoradiation therapy and its impact on survival. METHODS: Chemoradiation therapy entailed three cycles of full dose of gemcitabine (1000 mg/m(2) at days 1, 8, and 15, every 4 weeks) with 50-60 Gy radiation (2 Gy/day) at the main tumor and the regional and para-aortic lymph nodes. The present study included 25 patients. RESULTS: All of the patients were pathologically diagnosed before treatment. The relative dose intensity of gemcitabine was 84 %. The average dose of radiation was 53.8 Gy. Sixty percent of the patients underwent pancreatoduodenectomy, and 32 % underwent hemi-hepatectomy due to bile duct cancer (n = 24) or gall bladder cancer (n = 1). During neoadjuvant therapy, 21 patients (84 %) suffered from adverse events. The common hematological adverse events were leukopenia (44 %) and thrombocytopenia (32 %). It was necessary to exchange the plastic biliary stent in 11 patients (44 %). An R0 resection was achieved in 96 % of the patients, with pathological lymph node metastasis noted in 16 %. Moderate or marked histological changes were noted in 32 % of the patients. The 3-year overall survival rate after the first treatment was 74.6 %, with a 3.2-year observation period. CONCLUSIONS: Neoadjuvant therapy was feasible and is expected to improve survival by controlling regional extension. PMID- 26547916 TI - Short-term effects of fine particulate air pollution on cardiovascular hospital emergency room visits: a time-series study in Beijing, China. AB - BACKGROUND: The link between particulate matter (PM) and cardiovascular morbidity has been investigated in numerous studies. Less evidence exists, however, about how age, gender and season may modify this relationship. The aim of this study was to evaluate the association between ambient PM2.5 (PM <= 2.5 um) and daily hospital emergency room visits (ERV) for cardiovascular diseases in Beijing, China. Moreover, potential effect modification by age, gender, season, air mass origin and the specific period with 2008 Beijing Olympic were investigated. Finally, the temporal lag structure of PM2.5 has also been explored. METHODS: Daily counts of cardiovascular ERV were obtained from the Peking University Third Hospital from January 2007 to December 2008. Concurrently, data on PM2.5, PM10 (PM <= 10 um), nitrogen dioxide and sulfur dioxide concentrations were obtained from monitoring networks and a fixed monitoring station. Poisson regression models adjusting for confounders were used to estimate immediate, delayed and cumulative air pollution effects. The temporal lag structure was also estimated using polynomial distributed lag (PDL) models. We calculated the relative risk (RR) for overall cardiovascular disease ERV as well as for specific causes of disease; and also investigated the potential modifying effect of age, gender, season, air mass origin and the period with 2008 Beijing Olympics. RESULTS: We observed adverse effects of PM2.5 on cardiovascular ERV--an IQR increase (68 MUg/m(3)) in PM2.5 was associated with an overall RR of 1.022 (95% CI 0.990 1.057) obtained from PDL model. Strongest effects of PM2.5 on cardiovascular ERV were found for a lag of 7 days; the respective estimate was 1.012 (95% CI 1.002 1.022). The effects were more pronounced in females and in spring. Arrhythmia and cerebrovascular diseases showed a stronger association with PM2.5. We also found stronger PM-effects for stagnant and southern air masses and the period of Olympics modified the air pollution effects. CONCLUSIONS: We observed a rather delayed effect of PM2.5 on cardiovascular ERV, which was modified by gender and season. Our findings provide new evidence about effect modifications and may have implications to improve policy making for particulate air pollution standards in Beijing, China. PMID- 26547918 TI - Adalimumab Efficacy in Patients with Psoriasis Who Received or Did Not Respond to Prior Systemic Therapy: A Pooled Post Hoc Analysis of Results from Three Double Blind, Placebo-Controlled Clinical Trials. AB - INTRODUCTION: There are limited data from randomized controlled clinical trials on the outcomes of biologics after discontinuation of a different systemic therapy. To determine the efficacy of adalimumab in patients who previously received systemic therapy (including failed therapy), we performed a pooled post hoc analysis of Psoriasis Area and Severity Index (PASI) response data from three double-blind, placebo-controlled clinical trials in patients with moderate to severe psoriasis. METHODS: Patients from the M02-528, REVEAL, and CHAMPION studies who were previously exposed to systemic treatment were categorized based on their response. The efficacy of adalimumab compared with placebo was analyzed at the end of the double-blind treatment period for the overall pooled intent-to treat population (N = 1469) and subgroups that received (n = 780) or did not respond to (n = 229) previous systemic pretreatments. RESULTS: Rates for an improvement of >=75% from baseline in the PASI score (PASI75 response) were significantly greater (p < 0.001) at week 16 in patients treated with adalimumab compared with patients who received placebo in the overall (72.1 vs. 8.0%, respectively), previously treated (72.7 vs. 8.5%), and previously failed treatment (70.4 vs. 8.1%) groups. PASI75 response rates were similar in the overall group and in patients who did not respond to methotrexate, cyclosporine, or psoralen plus ultraviolet A therapy. Improvements of >=90 or >=100 % from baseline PASI score were also higher with adalimumab vs. placebo in previously treated patients. Adverse events were similar among subgroups. CONCLUSIONS: Adalimumab was efficacious for the treatment of moderate to severe psoriasis regardless of prior exposure to systemic therapies or failure of those prior therapies. CLINICALTRIALS. GOV IDENTIFIERS: NCT00645814, NCT00237887, NCT00235820. PMID- 26547919 TI - Coffee Consumption and Melanoma: A Systematic Review and Meta-Analysis of Observational Studies. AB - BACKGROUND: Laboratory and animals studies have suggested a possible protective effect of coffee consumption on the development of melanoma. However, the results of epidemiological studies investigating this association have been inconclusive. OBJECTIVE: A systematic review and meta-analysis of published studies was conducted to evaluate any association between coffee consumption and melanoma. METHODS: Observational studies were searched for in MEDLINE, EMBASE, and the Cochrane Central Register from inception to September 1, 2015. The Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed in conducting this study. RESULTS: We identified nine observational studies with a total of 927,173 study participants, of which 3787 had melanoma. With random effects modeling, the pooled relative risks (RR) for melanoma among regular coffee drinkers was 0.75 (95 % confidence interval [CI] 0.63-0.89, p = 0.001) compared with controls. Visual inspection of a funnel plot suggested publication bias, although Egger's test (p = 0.981) delineated no small-study effects. The pooled relative risks for melanoma among decaffeinated coffee drinkers was, however, not statistically significant at 0.92 (95 % CI 0.82-1.05, p = 0.215). CONCLUSION: There is some evidence for the beneficial effects of regular coffee consumption on melanoma. More prospective cohort studies with systematic quantification of coffee consumption would be necessary to further elucidate this association. PMID- 26547920 TI - Readers with Autism Can Produce Inferences, but they Cannot Answer Inferential Questions. AB - Readers with autism (ASD), poor comprehension (PC), and typical development (TD) took part in three reading experiments requiring the production of inferences. In Experiments 1 and 2 reading times for target phrases-placed immediately after text implicitly indicating the emotion of a protagonist or after a number of filler sentences, respectively--were used as measures of inferencing. In Experiment 3, participants were explicitly asked to identify the protagonist's emotion. There were no significant differences among groups in Experiment 1. Compared to TD readers, the PC group performed poorly in Experiments 2 and 3. ASD readers performed worse than PC participants only in the explicit-question task. Although ASD readers can produce inferences, they respond to questions about them with difficulty. PMID- 26547921 TI - Health Services Utilization Among Children With and Without Autism Spectrum Disorders. AB - Using data from multiple health systems (2009-2010) and the largest sample to date, this study compares health services use among youth with and without an autism spectrum disorder (ASD)-including preventive services not previously studied. To examine these differences, we estimated logistic and count data models, controlling for demographic characteristics, comorbid physical health, and mental health conditions. Results indicated that youth with an ASD had greater health care use in many categories, but were less likely to receive important preventive services including flu shots and other vaccinations. An improved understanding of the overall patterns of health care use among this population could enable health systems to facilitate the receipt of appropriate and effective health care. PMID- 26547922 TI - Prediction of Antimalarial Drug Clearance in Children: A Comparison of Three Different Interspecies Scaling Methods. AB - BACKGROUND AND OBJECTIVE: Allometric scaling is extensively used for the prediction of pharmacokinetic parameters from animals to humans and is often used for the selection of first-in-human dose. Allometric scaling can also be used to predict a pharmacokinetic parameter in children from adult data including animal species such as rat and dog. The current study was undertaken to evaluate if the clearances of antimalarial drugs in children with malaria can be predicted allometrically (interspecies scaling) from adult rat, dog, and human adult (healthy as well patients with malaria) clearance values. METHODS: Three methods [simple allometry, maximum lifespan potential (MLP), and MLP with an empirical correction factor] using clearance values from adult rat, dog, and adult humans with and without malaria were used for the prediction of antimalarial drug clearance in children with malaria. RESULTS: The results of this study indicated that the simple allometry would systematically over-predict antimalarial drug clearance in children with malaria whereas the application of MLP would under predict the clearances of these drugs in children. Therefore, an empirical correction factor was introduced to MLP which substantially improved the antimalarial drug clearances in children. CONCLUSIONS: Overall, the results of the study indicated that interspecies scaling using adult rat, dog, and human clearance values of antimalarial drugs could possibly be used to predict drug clearance in children with malaria of different age groups and may be useful during pediatric drug development of antimalarial drugs. PMID- 26547923 TI - Attentional bias to threat in children at-risk for emotional disorders: role of gender and type of maternal emotional disorder. AB - Previous studies suggested that threat biases underlie familial risk for emotional disorders in children. However, major questions remain concerning the moderating role of the offspring gender and the type of parental emotional disorder on this association. This study addresses these questions in a large sample of boys and girls. Participants were 6-12 years old (at screening) typically developing children participating in the High Risk Cohort Study for Psychiatric Disorders (n = 1280; 606 girls, 674 boys). Children were stratified according to maternal emotional disorder (none; mood disorder; anxiety disorder; comorbid anxiety/mood disorder) and gender. Attention biases were assessed using a dot-probe paradigm with threat, happy and neutral faces. A significant gender by-parental emotional disorder interaction predicted threat bias, independent of anxiety and depression symptoms in children. Daughters of mothers with an emotional disorder showed increased attention to threat compared with daughters of disorder-free mothers, irrespective of the type of maternal emotion disorder. In contrast, attention bias to threat in boys only occurred in mothers with a non comorbid mood disorder. No group differences were found for biases for happy-face cues. Gender and type of maternal emotional disorder predict attention bias in disorder-free children. This highlights the need for longitudinal research to clarify whether this pattern of threat-attention bias in children relates to the risk of developing anxiety and mood disorders later in life. PMID- 26547924 TI - Factors associated with medical student clinical reasoning and evidence based medicine practice. AB - OBJECTIVES: To identify the factors associated with medical students' clinical reasoning (CR) use and evidence-based medicine (EBM) use in the clinical setting. METHODS: Our cross-sectional study surveyed 44 final-year medical students at an emerging academic medical center in Singapore. We queried the students' EBM and CR value and experiences in the classroom and clinical settings. We compared this to their perceptions of supervisors' value and experiences using t-tests. We developed measures of teaching culture and practice culture by combining relevant questions into summary scores. Multivariate linear regression models were applied to identify factors associated with the students' CR and EBM clinical use. RESULTS: Eighty-nine percent of students responded (n=39). Students reported valuing CR (p=0.03) and EBM (p=0.001) more than their supervisors, but practiced these skills similarly (p=0.83; p=0.82). Clinical practice culture and classroom CR experience were independently associated with students' CR clinical use (p=0.05; p=0.04), and classroom EBM experience was independently associated with students' EBM clinical use (p=0.03). Clinical teaching culture was not associated with students' CR and EBM clinical use. CONCLUSIONS: Our study found that medical students' classroom experience and the clinical practice culture influenced their CR and EBM use. The clinical teaching culture did not. These findings suggest that in order to increase student CR and EBM use, in addition to providing classroom experience, medical educators may need to change the hospital culture by encouraging supervisors to use these skills in their clinical practice. PMID- 26547925 TI - Health-related quality of life of students from a private medical school in Brazil. AB - OBJECTIVES: To assess health-related quality of life (HRQOL) and to describe factors associated with its variation among undergraduate medical students at a Brazilian private medical school. METHODS: A cross-sectional study in a sample (n=180) of medical students at a private medical school in Salvador, Brazil, stratified by year of medical course. Data about age, sex, year of course, physical activity, sleepiness, headaches, participation in a student loan program supported by the Brazilian government (FIES) and living arrangements were collected using a self-administered form. HRQOL was assessed by using a Brazilian Portuguese version of the SF-36 form. The eight domains of SF-36 and the Physical Component (PCS) and Mental Component (MCS) Summaries scales were calculated. RESULTS: The medical students showed poor HRQOL, mainly because of the mental component. Lower mean scores were found among those with FIES support, females, those suffering from sleepiness, headaches and lacking physical activity. No clear trend was observed in the variation of the SF-36 mean scores according to the year of medical school. However, students in the fifth year of the course had the highest HRQOL mean scores. CONCLUSIONS: Health-related quality of life of students at this private medical school was poor, mainly because of its mental component. Lower HRQOL was associated with FIES support, females, sleepiness, headaches and lack of regular physical activity. Higher scores were found among fifth year students. PMID- 26547926 TI - NCI Funding Trends and Priorities in Physical Activity and Energy Balance Research Among Cancer Survivors. AB - There is considerable evidence that a healthy lifestyle consisting of physical activity, healthy diet, and weight control is associated with reduced risk of morbidity and mortality after cancer. However, these behavioral interventions are not widely adopted in practice or community settings. Integrating heath behavior change interventions into standard survivorship care for the growing number of cancer survivors requires an understanding of the current state of the science and a coordinated scientific agenda for the future with focused attention in several priority areas. To facilitate this goal, this paper presents trends over the past decade of the National Cancer Institute (NCI) research portfolio, fiscal year 2004 to 2014, by funding mechanism, research focus, research design and methodology, primary study exposures and outcomes, and study team expertise and composition. These data inform a prioritized research agenda for the next decade focused on demonstrating value and feasibility and creating desire for health behavior change interventions at multiple levels including the survivor, clinician, and healthcare payer to facilitate the development and implementation of appropriately targeted, adaptive, effective, and sustainable programs for all survivors. PMID- 26547928 TI - RE: Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. PMID- 26547927 TI - Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib. AB - BACKGROUND: Little is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug. METHODS: We measured risk using drug-related adverse events that were grade 3 or higher, benefit by objective response rate, and trial outcomes by whether studies met their primary endpoint with acceptable safety. The differences in risk (death rate) and benefit (overall response rate) between industry and nonindustry trials were analyzed with an inverse-variance weighted fixed effects meta-analysis implemented as a weighted regression analysis. All statistical tests were two-sided. RESULTS: We identified 103 primary publications of sunitinib monotherapy, representing 9092 patients and 3991 patient-years of involvement over 10 years and 32 different malignancies. In total, 1052 patients receiving sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence interval [CI] = 15.3% to 16.0%), 98 died from drug-related toxicities (1.08%, 95% CI = 1.02% to 1.14%), and at least 1245 experienced grade 3-4 drug-related toxicities (13.7%, 95% CI = 13.3% to 14.1%). Risk/benefit worsened as the development program matured, with several instances of replicated negative studies and almost no positive trials after the first responding malignancies were discovered. CONCLUSIONS: Even for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication. PMID- 26547929 TI - Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma. AB - MicroRNA-9 (miR-9) dysregulation is implicated in a variety of human malignancies including hepatocellular carcinoma (HCC), but its role remains contradictory. In this study, we explored the expression and methylation status of miR-9 in HCC samples, as well as the tumor-related functions of miR-9 in vitro. Bioinformatics analysis, array-based RNA expression profile, and literature retrieval were used to identify miR-9 targets in HCC. The potential downstream candidates were then validated by luciferase reporter assay, real-time quantitative PCR, and western blot or enzyme linked immunosorbent assay (ELISA). The expression status and clinicopathologic significances of miR-9 target genes in clinical samples were further explored. The results showed that miR-9 was frequently downregulated in primary HCC. Its silencing was largely contributed by a high frequency (42.5%) of mir-9-1 hypermethylation, which was correlated with bigger tumor size (P = 0.0234). In vitro functional studies revealed that miR-9 restoration retarded HCC cell proliferation and migration. IL-6, AP3B1, TC10, ONECUT2, IGF2BP1, MYO1D, and ANXA2 were confirmed to be miR-9 targets in HCC. Among them, ONECUT2, IGF2BP1, and ANXA2 were confirmed to be aberrantly upregulated in HCC. Moreover, upregulation of ONECUT2, IGF2BP1, and IL-6 were significantly associated with poor post-surgery prognosis (P = 0.0458, P = 0.0037 and P = 0.0461, respectively). Mechanically, miR-9 plays a tumor suppressive role partially through a functional miR-9/IGF2BP1/AKT&ERK axis. Our study suggests that miR-9 functions as a tumor suppressor in HCC progression by inhibiting a series of target genes, including the newly validated miR-9/IGF2BP1/AKT&ERK axis, thus providing potential therapeutic targets and novel prognostic biomarkers for HCC patients. PMID- 26547930 TI - Effects of Use of a Continuous Positive Airway Pressure Device on Glaucoma. AB - BACKGROUND: The aim of this study was to investigate the prevalence of glaucoma in obstructive sleep apnea syndrome (OSAS) and to determine the efficacy of the equipment used in the treatment of this disease. MATERIAL AND METHODS: In this cross-sectional study, 38 patients with OSAS used the continuous positive airway pressure (CPAP) device (Group 1) and 32 patients with OSAS refused CPAP device (Group 2). Thirty-six patients did not have OSAS (Group 3). RESULTS: Patient age, gender, height, weight, and neck circumference did not differ among groups (p>0.05); and the apnea-hypopnea index (AHI) and respiratory disturbance index (RDI) values did not differ between Groups 1 and 2 (p>0.05). Vision and pachymetric values did not differ among groups (p>0.05). The IOP was significantly higher in Group 2 than in Group 1 (p<0.05) but did not differ between Groups 1 and 3 (p>0.05). The fundus C/D ratio was significantly higher (p<0.05) in Group 2 than in the other groups but did not differ between Groups 1 and 3 (p>0.05). In Group 1, 2, and 3, 5.2%, 12.5%, and 0%, respectively, of patients had glaucoma. CONCLUSIONS: OSAS should be considered a significant risk factor for glaucoma. Eye tests may help to identify individuals with undiagnosed OSAS, and such testing of patients with diagnosed OSAS may allow early detection of glaucoma and referral of such patients for CPAP therapy to prevent development of complications. PMID- 26547931 TI - Cancer Prevention: Obstacles, Challenges and the Road Ahead. AB - Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention. The latter is the topic of this Commentary and spans a broad range of activities. The genetic heterogeneity and complexity of advanced cancers strongly support the rationale for early interruption of the carcinogenic process and an enhanced focus on prevention as a priority strategy to reduce the burden of cancer; however, the focus of cancer prevention management should be on individuals at high risk and on primary localized disease in which screening and detection should also play a vital role. The timing and dose of (chemo-)preventive intervention also affects response. The intervention may be ineffective if the target population is very high risk or already presenting with preneoplastic lesions with cellular changes that cannot be reversed. The field needs to move beyond general concepts of carcinogenesis to targeted organ site prevention approaches in patients at high risk, as is currently being done for breast and colorectal cancers. Establishing the benefit of new cancer preventive interventions will take years and possibly decades, depending on the outcome being evaluated. We also propose that comparative effectiveness research designs and the value of information obtained from large-scale prevention studies are necessary in order for preventive interventions to become a routine part of cancer management. PMID- 26547932 TI - Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment. AB - BACKGROUND: Central nervous system (CNS) metastases represent a major problem in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer because of the disappointing efficacy of HER2-targeted therapies against brain lesions. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases. METHODS: We treated female nude mice bearing BT474 or MDA-MB 361 brain metastases (n = 9-11 per group) or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. Data were analyzed with one-way analysis of variance (ANOVA), Kaplan-Meier analysis, and Coefficient of Determination. All statistical tests were two-sided. RESULTS: T-DM1 delayed the growth of HER2-positive breast cancer brain metastases compared with trastuzumab. These findings were consistent between HER2-driven and PI3K-driven tumors. The activity of T-DM1 resulted in a survival benefit (median survival for BT474 tumors: 28 days for trastuzumab vs 112 days for T-DM1, hazard ratio = 6.2, 95% confidence interval = 6.1 to 85.84, P < .001). No difference in drug distribution or HER2-signaling was revealed between the two groups. However, T-DM1 led to a statistically significant increase in tumor cell apoptosis (one-way ANOVA for ApopTag, P < .001), which was associated with mitotic catastrophe. CONCLUSIONS: T DM1 can overcome resistance to trastuzumab therapy in HER2-driven or PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. Clinical investigation of T-DM1 for patients with CNS metastases from HER2 positive breast cancer is warranted. PMID- 26547934 TI - Robert P. Scholz, 1939-2015. PMID- 26547933 TI - ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis. AB - BACKGROUND: Cell surface sialylation is associated with tumor cell invasiveness in many cancers. Glioblastoma is the most malignant primary brain tumor and is highly infiltrative. ST3GAL1 sialyltransferase gene is amplified in a subclass of glioblastomas, and its role in tumor cell self-renewal remains unexplored. METHODS: Self-renewal of patient glioma cells was evaluated using clonogenic, viability, and invasiveness assays. ST3GAL1 was identified from differentially expressed genes in Peanut Agglutinin-stained cells and validated in REMBRANDT (n = 390) and Gravendeel (n = 276) clinical databases. Gene set enrichment analysis revealed upstream processes. TGFbeta signaling on ST3GAL1 transcription was assessed using chromatin immunoprecipitation. Transcriptome analysis of ST3GAL1 knockdown cells was done to identify downstream pathways. A constitutively active FoxM1 mutant lacking critical anaphase-promoting complex/cyclosome ([APC/C]-Cdh1) binding sites was used to evaluate ST3Gal1-mediated regulation of FoxM1 protein. Finally, the prognostic role of ST3Gal1 was determined using an orthotopic xenograft model (3 mice groups comprising nontargeting and 2 clones of ST3GAL1 knockdown in NNI-11 [8 per group] and NNI-21 [6 per group]), and the correlation with patient clinical information. All statistical tests on patients' data were two-sided; other P values below are one-sided. RESULTS: High ST3GAL1 expression defines an invasive subfraction with self-renewal capacity; its loss of function prolongs survival in a mouse model established from mesenchymal NNI-11 (P < .001; groups of 8 in 3 arms: nontargeting, C1, and C2 clones of ST3GAL1 knockdown). ST3GAL1 transcriptomic program stratifies patient survival (hazard ratio [HR] = 2.47, 95% confidence interval [CI] = 1.72 to 3.55, REMBRANDT P = 1.92 x 10-8; HR = 2.89, 95% CI = 1.94 to 4.30, Gravendeel P = 1.05 x 10-11), independent of age and histology, and associates with higher tumor grade and T2 volume (P = 1.46 x 10-4). TGFbeta signaling, elevated in mesenchymal patients, correlates with high ST3GAL1 (REMBRANDT gliomacor = 0.31, P = 2.29 x 10-10; Gravendeel gliomacor = 0.50, P = 3.63 x 10-20). The transcriptomic program upon ST3GAL1 knockdown enriches for mitotic cell cycle processes. FoxM1 was identified as a statistically significantly modulated gene (P = 2.25 x 10-5) and mediates ST3Gal1 signaling via the (APC/C)-Cdh1 complex. CONCLUSIONS: The ST3GAL1-associated transcriptomic program portends poor prognosis in glioma patients and enriches for higher tumor grades of the mesenchymal molecular classification. We show that ST3Gal1-regulated self-renewal traits are crucial to the sustenance of glioblastoma multiforme growth. PMID- 26547935 TI - [Laparoscopic gastrointestinal surgery: 2D and 3D vs. robot-assisted. Robot assisted surgery is superior to 2D and 3D laparoscopic surgery]. PMID- 26547936 TI - [2D laparoscopy is in accordance with China' national conditions]. PMID- 26547938 TI - [Total laparoscopic operation]. PMID- 26547937 TI - [Laparoscopic distal gastrectomy with Billorth I reconstruction for gastric cancer: small incision assisted vs. total laparoscopy. Small incision assisted laparoscopic operation]. PMID- 26547939 TI - [Should Denonvilliers' fascia be preserved during laparoscopic radical surgery for rectal cancer? Value and feasibility of preserving Denonvilliers' fascia]. PMID- 26547940 TI - [Disection of partial Denonvilliers' fascia ensures better circumferential resection margin]. PMID- 26547941 TI - [Is protective stoma necessary after low anterior resection for rectal cancer? Protective stoma: disadvantages outweigh advantages]. PMID- 26547942 TI - [The benefits of protective stoma outweigh the costs]. PMID- 26547944 TI - [Sleeve gastrectomy followed by gastric bypass if necessary]. PMID- 26547943 TI - [Selection of laparoscopic bariatric procedures in patients with a body mass index of 50 and higher. Definitive gastric bypass is superior to two-stage operation]. PMID- 26547945 TI - [Chinese consensus of enhanced recovery after surgery for colorectal surgery (2015)]. AB - The Chinese consensus of enhanced recovery after surgery for colorectal surgery (2015) is the first guideline in the area of enhanced recovery after surgery (ERAS) in colorectal surgery in China, which is drafted by a committee organized by the China ERAS Group of GSPEN. The concept of ERAS is a series of evidence based perioperative treatment to reduce the stress of the patients both physically and psychologically and then achieve rapid recovery. This is a new concept in the 21st century which is a revolution to the medical treatment and rehabilitation mode. There are a lot of benefits in ERAS: (1)More effective treatment; (2)Less postoperative complications; (3)Accelerating rehabilitation; (4)Shortening of hospital stay; (5)Reduction of medical expenses; (6)Relief of the financial burden both on the family hood and the social security system. With the successful application of ERAS in colorectal surgery, both literature and clinical experiences are reviewed by the committee to draft this consensus. PMID- 26547946 TI - [ACTION OF MODULATORS OF LARGE-CONDUCTANCE Ca2+-ACTIVATED K+ CHANNELS ON RAT ASCITES HEPATOMA CELLS AND ISOLATED RAT LIVER MITOCHONDRIA TREATED BY Cd2+]. AB - ATP-producing cell organelles, mitochondria, are the primary target for heavy metals which are major environmental pollutants and cause various pathological conditions and diseases. It has been established that the mechanism of toxic action of heavy metals, includes changes in the intracellular production of reactive oxygen species and mitochondrial dysfunction mediated by disturbances of the respiratory chain and by activation of Ca2+-dependent nonselective pore of the inner mitochondrial membrane. The role of other ion channels, in particular such selective potassium channels as Ca2+ activated large-conductance potassium channels, BK(Ca), considered to be <> for a cell, is practically not investigated. In the present work on rat ascites hepatoma AS-30D cells and isolated rat liver mitochondria we studied action of different BK(Ca) effectors in the absence and presence of Cd2+ in the assay medium, namely of two its openers, N51619 and N5004,and one blocker, paxilline. After 24 h-incubation of AS 30D cells with 10 uM of either NS 1619 or N5004, the number of apoptotic cells was found to increase compared with control. Besides, the presence of these BK(Ca) openers in the media produced an additive effect on Cd2+-induced apoptosis of AS-30D cells. The same concentration of N51619 and N5004 did not affect significantly respiration ofAS-30D cells after 3, 24 and 48 h of incubation but produced a substantial increase in intracellular production of reactive oxygen species after 3 h of the treatment. In experiments on isolated rat liver mitochondria NS1619 and N5004, added at the same concentration to the KCI containing medium, had no effect on the respiratory rate at state 3 by Chance and on the maximally uncoupled respiration rate (both in the presence and absence of Cd2+); at the same time they induced a weak uncoupling action by accelerating the basal respiration and the resting state respiration (at state 4 by Chance) as well as they enlarged the high-amplitude mitochondrial swelling induced by Cd2+ in this medium. It was shown that paxilline, at concentration of 1 uM, decreased the mortality of AS-30D cells after 3, 24 and 48 h of incubation in the presence of Cd2+ and enhanced intracellular production of reactive oxygen species in control cells after 3 and 24 h of incubation. At concentration producing a long term protective effeet, paxilline did not influence the respiration of AS-30D cells and isolated rat liver mitochondria (both in the presence and absence of Cd2+) and did not decrease mitochondrial swelling observed in the presence of Cd2+ and the BK(Ca) activators. Possible molecular mechanisms of action of the BK(Ca) modulators are discussed. PMID- 26547947 TI - [ELEMENTS OF THE LOW MOLECULAR WEIGHT CHAIN OF ANTIOXIDANT DEFENSE IN TISSUES OF THE BLACK SEA MOLLUSC ANADARA KAGOSHIMENSIS BRUGUIERE]. AB - The content of reduced glutathione (GSH) and the activity of the coupled with it antioxidant enzymes - glutathione peroxidase and glutathione reductase as well the level of glucose, carbamide and amino acids were investigated in the hepatopancreas, gills and foot of the Black, Sea mollusk Anadara kagoshimensis. The highest content of GSH and the highest activity of glutathione peroxidase were found in mollusk foot, evidencing the active antioxidant role of glutathione played both within composition of this enzyme and independently. The maximal content of glucose, amino acids and carbamide was in the hepatopancreas and gills and the minimal - in the anadara's foot. The possible involvement and role of these low molecular weight antioxidants in the defense of mollusk tissues against action of free radical oxidation and in providing adaptation reactions of anadara in hypoxic habitats are considered. Key words: antioxidant complex, glutathione, glucose, carbamide, amino acids, anadara Anadara kagoshimensis, Black Sea. PMID- 26547948 TI - [THE THYROID STATUS OF RATS IMMUNIZED WITH PEPTIDES DERIVED FROM THE EXTRACELLULAR REGIONS OF THE TYPES 3 AND 4 MELANOCORTIN RECEPTORS AND THE 1B SUBTYPE 5-HYDROXYTRYPTAMINE RECEPTOR]. AB - The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5 hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5 HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased level of TSH. Our data on the negative impact of long-term immunization of rats with BSA-conjugated peptides derived from the extracellular regions of M4R, M3R.and 5-HT1BR on their thyroid status is a strong argument in favor of participation of these receptors and intracellular signaling pathways associated with them in the regulation of HPT axis. PMID- 26547949 TI - [PHOSPHOLIPIDS AND FATTY ACIDS IN ERYTHROCYTES OF THE LAMPREY LAMPETRA FLUVIATILIS DURING AUTUMN PRESPAWNING PERIOD AND THE ABSORPTION SPECTRUM OF THEIR LIPID EXTRACT]. AB - The content of some classes of phospholipids and their fatty acid composition in erythrocytes of the lamprey Lampetrafluviatilis during the autumn period of its prespawning migration are investigated. It is found that the phospholipid spectrum of erythrocytes of the lamprey, the oldest representative of vertebrates, is similar to that of many mammals. A four-fold prevalence of phosphatidilcholine content over sphingomyelin content as well as prevalence of (omega3-acids over omega6-acids indicates the <> of lamprey's erythrocyte membranes - an important indicator of deformational ability of lamprey's erythrocytes. Phosphatidilethanol amine and its plasmalogenic form are the most unsaturated phospholipids (their unsaturation indices are 230 and 342, correspondingly). Phosphatidilcholine is the most saturated one (UI is 167). It is found that the basic acid indicators characterizing the fluidity of erythrocyte membranes remain unchanged during the whole period of prespawning migration of lampreys up to spawning. The blood contains several buffer systems, in particular, membrane phospholipids which neutralize acids and alkali incoming into the blood. In the process of organism life a change of pH inside erythrocytes occurs. One can suppose that the base of the system associated with buffer properties of the blood is water dissociation. Inside thin vessels of the circulatory system the hemoglobin attaches and returns molecules of oxygen due to interaction of the buffer systems with water. The property of water to dissociate as well as ion transfer produce in erythrocytes, lying within narrow vessels of the circulatory system, a local pH alteration allowing displacing/attaching the molecule of oxygen from hemoglobin. PMID- 26547950 TI - [HOMOCYSTEINE-INDUCED MEMBRANE CURRENTS, CALCIUM RESPONSES AND CHANGES OF MITOCHONDRIAL POTENTIAL IN RAT CORTICAL NEURONS]. AB - Homocysteine, a sulfur-containing amino acid, exhibits neurotoxic effects and is involved in the pathogenesis of several major neurodegenerative disorders. In contrast to well studied excitoxicity of glutamate, the mechanism of homocysteine neurotoxicity is not clearly understood. By using whole-cell patch-clamp, calcium imaging (fluo-3) and measurements of mitochondrial membrane potential (rhodamine 123) we studied transmembrane currents, calcium signals and changes in mitochondrial membrane potential induced by homocysteine versus responses induced by NMDA and glutamate in cultured rat cortical neurons. L-homocysteine (50 uM) induced inward currents that could be completely blocked by the selective antagonist of NMDA receptors - AP-5. In contrast to NMDA-induced currents, homocysteine-induced currents had a smaller steady-state amplitude. Comparison of calcium responses to homocysteine, NMDA or glutamate demonstrated that in all cortical neurons homocysteine elicited short, oscillatory-type calcium responses, whereas NMDA or glutamate induced sustained increase of intracellular calcium. Analysis of mitochondrial changes demonstrated that in contrast to NMDA homocysteine did not cause a drop of mitochondrial membrane potential at the early stages of action. However, after its long-term action, as in the case of NMDA and glutamate, the changes in mitochondrial membrane potential were comparable with the full drop of respiratory chain induced by protonophore FCCP. Our data suggest that in cultured rat cortical neuron homocysteine at the first stages of action induces neurotoxic effects through activation of NMDA-type ionotropic glutamate receptors with strong calcium influx through the channels of these receptors. The long-term action of homocysteine may lead to mitochondrial disfuction and appears as a drop of mitochondrial membrane potential. PMID- 26547951 TI - [DIFFERENCES IN ADAPTIVE BEHAVIORS IN ADOLESCENT MALE AND FEMALE RATS EXPOSED AS NEWBORNS TO INFLAMMATORY PAIN OR STRESS]. AB - In adolescent rats (25-35-day-old) exposed as newborns (the first and repeatedly second days) to adverse impacts (inflammatory pain, stress of short-term maternal separation or their combination) sex dimorphism was revealed in pain behavior under conditions of similar peripheral inflammation. According to the priority data obtained, strengthening of pain-related response in the formalin test was found in males, whereas pain sensitivity in females was not changed, that is pain experienced by them as newborns did not affect the system reactivity to the same chemical irritant in the adolescent period. However, the rats of both sexes, who experienced short-term stress of maternal deprivation (60 min-during the first and the second days of life), displayed increased pain sensitivity in the formalin test. Combined effect of inflammatory pain and maternal deprivation in newborns did not alter pain sensitivity in both adolescent males and adolescent females. The male and female rats exposed as newborns to maternal deprivation displayed a decrease of the anxiety level in the elevated plus maze; the rats, exposed to each of the above-mentioned early impacts showed a decline of adaptive behavior in the forced swimming test; the males exposed to pain and combined impacts demonstrated impairment of spatial learning in Morris labyrinth. Thus, we pioneered in demonstrating sex differences in the effects of inflammatory pain in newborn pups on pain sensitivity in the formalin test in adolescent rats. Separation of the influence of early stress or pain was revealed in adolescent females in the formalin test: maternal deprivation induced hyperalgesia, whereas pain failed to change functional activity of the tonic nociceptive system. PMID- 26547952 TI - [STUDY OF THE EFFICACY OF REGULATION OF THE BLOOD SERUM PHYSICOCHEMICAL PARAMETERS IN CHILDREN WITH DYSFUNCTION OF PHYSIOLOGICAL SYSTEMS]. AB - The physicochemical parameters of blood serum (osmolality, concentration of several ions, total protein, glucose) were studied in 200 children of different age with various forms of pathology. The variability of each parameter was calculated. A high level of stability of the parameters studies was revealed in healthy children and in children with dysfunction of various systems (disease of the respiratory system, gastrointestinal tract, renal and urinary tract, nervous and endocrine systems). However, estimation of their coefficients of variation showed significant individual deviations of these parameters from the average value of the examined patients. This fact reflects the extent of efficacy of activity of different organs and regulatory systems under pathological processes. Combination of clinical and ontogenetic methods of evolutionary physiology in this study opens new possibilities for understanding the nature of regulation of water-salt balance in humans and points out to the expedience of using these approaches in the practical medicine. PMID- 26547953 TI - [VOCALIZATIONS OF SEX PARTNERS IN THE HOUSE MOUSE (MUS MUSCULUS)]. AB - Acoustic parameters of the house mouse male and female vocalizations accompanying the sexual behavior were studied. The spectral-temporal analysis of female defensive call and male ultrasound call was carried out for adult house mice- hybrids of outbreed strains CBA and C57B1/6. The principal feature of the female defensive call is its harmonic structure formed by three--five main harmonics with the fundamental frequency about 3 kHz. The major energy of the signal is concentrated below 25 kHz. The basic harmonic structure could be modified by frequency and amplitude modulation or/and.noise. Call duration varied widely from 40 up to 470 ms with the average value of 180 +/- 70 ins. The principal feature of male ultrasound vocalization is its low intensity and rareness of noise components. Depending on semantic load of the call, its fundamental frequency averaged 67.3 +/- 8.5 or 45.6 +/- 3.7 kHz. Male ultrasound vocalizations were shorter than female defensive calls and their duration did not exceed 220 ms. Key words: house mouse, acoustic structure of vocalizations, sexual behavior, sound and ultrasound vocalizations of rodents. PMID- 26547954 TI - [CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY]. AB - Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin). PMID- 26547955 TI - [SPECIFICITY OF CONTENT AND MORPHOLOGY OF PERIPHERAL BLOOD CELLS IN THREE BAT SPECIES OF KARELIA DURING HIBERNATION]. AB - Pronounced leukopenia during hibernation was found in bats (Chiroptera) of Karelia - brown long-eared bat (Plecotus auritus), Brandt's bat (Myotis brandtii) and northern bat (Eptesicus nilssoni). A higher content of lymphocytes, eosinophils and basophils was revealed in the northern bat featuring an increased resistance to cold as compared to the Brandt's bat and the brown long-eared bat. The differences in ratio of particular lymphocyte types may be related to biological, ecological and physiological peculiarities of the species studied. PMID- 26547956 TI - [SENSITIZATION OF NICOTINIC ACETYLCHOLINE RECEPTOR OF SOIL NEMATODE CAENORHABDITIS ELEGANS THROUGH ACTIVATION OF MUSCARINIC RECEPTORS BY ARECOLINE]. PMID- 26547957 TI - [CHANGE IN THE PARAMETERS OF CALLING SONG OF THE CRICKET GRYLLUS BIMACULATUS DEG. IN THE PROCESS OF INDIVIDUAL DEVELOPMENT]. PMID- 26547958 TI - STABILITY OF NATIVE AND MODIFIED alpha-GALACTOSIDASE OF Cladosporium cladosporioides. AB - By modifying carbohydrate component of glycoproteins it is possible to elucidate its role in manifestation of structural and functional properties of the enzyme. The comparison of activity and stability of the native and modified by oxidation with sodium periodate alpha-galactosidase of Cladosporium cladosporioides was carried out. To determine alpha-galactosidase activity the authors used n nitrophenyl synthetic substrate, as well as melibiose; raffinose and stachyose. Modification of the carbohydrate component had a significant effect on catalytic properties of the enzyme. Both the reduction of V and enzyme affinity for natural and synthetic substrates were observed The native enzyme retained more than 50% ofthe maximum activity in the range of 20-60 degrees C, while for the modified enzyme under the same conditions that temperature range was 30-50 degrees C. The modified alpha-galactosidase demonstrated a higher thermal stability under neutral pH conditions. The residual activity of the modified alpha-galactosidase was about 30% when treated with 70% (v/v) methanol, ethanol and propanol. About 50% of initial activity was observed when 40% ethanol and propanol, and 50% methanol were used. It was shown that the modification of C. cladosporioides alpha-galactosidase by sodium periodate is accompanied by a significant decrease in enzyme activity and stability, probably caused by topological changes in the tertiary and quaternary structure of the protein molecule. PMID- 26547959 TI - EFFECT OF DIPHTHERIA TOXIN T-DOMAIN ON ENDOSOMAL pH. AB - A key step in the mode of cytotoxic action of diphtheria toxin (DT) is the transfer of its catalytic domain (Cd) from endosomes into the cytosol. The main activity in this process is performed by the transport domain (Td), but the molecular mechanism of its action remains unknown. We have previously shown that Td can have some influence on the endosomal transport of DT The aim of this work was to study the effect of diphtheria toxin on the toxin compartmentalization in the intracellular transporting pathway and endosomal pH. We used recombinant fragments of DT which differed only by the presence of Td in their structure, fused with fluorescent proteins. It was shown that the toxin fragment with Td moved slower by the pathway early-late endosomes-lysosomes, and had a slightly different pattern of colocalization with endosomal markers than DT fragment without Td. In addition, endosomes containing DT fragments with Td had a constant pH of about 6.5 from the 10th to 50th minute of observation, for the same time endosomes containing DT fragments without Td demonstrated a decrease in pH from 6.3 to 5.5. These results indicate that Td inhibits acidification of endosomal medium. One of possible explanations for this may be the effect of the ion channel formed by the T-domain on the process of the endosomal acidification. This property of Td may not only inhibit maturation of endosomes but also inhibit activation of endosomal pH-dependent proteases, and this promotes successful transport of Cd into the cell cytosol. PMID- 26547960 TI - INHIBITORY POTENTIAL OF POLYHYDROXYLATED FULLERENES AGAINST PROTEIN TYROSINE PHOSPHATASE 1B. AB - Inhibition of PTP1B by polyhydroxylated fullerenes was studied in silico and in vitro. The enzyme kinetics in the presence of polyhydroxy small gap fullerenes showed that reciprocal value of maximum velocity non-linearly increases with increasing the inhibitor concentration. Analysis of the dose-dependent curve of PTP1B inhibition suggests an apparent positive cooperativity with involvement of at least two binding sites for the hydroxylated fullerene cages. Molecular docking calculations indicated that highly hydroxylated fullerene C60 may occupy the active site and additional allosteric binding site with similar affinity. In silico analysis of a number of fullerenols with 6, 12, 18, 24, 30, and 36 hydroxyl groups showed that the inhibitory activity may depend on the degree of hydroxylation of the nanoparticles surface. These data provide some understanding of the mechanisms of inhibitory action of fullerenols on activity of protein tyrosine phosphatases. PMID- 26547961 TI - BIOCHEMICAL MECHANISMS OF RESISTANCE TO p-NITROCHLOROBENZENE OF KARST CAVES MICROORGANISMS. AB - The biochemical mechanisms of resistance to persistent organic xenobiotic p nitrochlorobenzene (NCB) of bacterial strains isolated from two cave clays ecosystems-Mushkarova Yama (Podolia, Ukraine) and Kuybyshevskaya (Western Caucasus, Abkhazia) have been established It has been determined that chemoorganotrophic karst caves strains could interact with NCB and transform it reducing the nitro group withformation of p-chloroaniline (ClA) followed by further destruction of NCB aromatic ring. This explained high resistance of caves strains to NCB. The studied strains could potentially be used in wastewater treatment from nitrochloraromatic compounds. PMID- 26547962 TI - HEPATOPROTECTIVE ACTIVITY OF EXOGENOUS RNA. AB - Hepatoprotective activity of Nuclex, a pharmaceutical composed of low-molecular yeast RNA, was investigated during acute and chronic thioacetamide-induced hepatotoxicity. It is demonstrated, that Nuclex administration at a dose of 200 mg/kg during acute and chronic liver injury produces hepatoprotective effect, which is associated with decrease in liver parenchyma lesions and in its inflammatory infiltration. Nuclex application attenuates thioacetamide-induced free radical damage of hepatic biopolymers, expressed in the reduction of TBA reactive products, carbonyl derivatives, and recovery of protein thiol groups and reduced glutathione levels. PMID- 26547963 TI - THE SENSITIVITY OF CELLS WITH THE VARIOUS LEVEL OF NAD(P)H:QUINONE OXIDOREDUCTASE 1 TO CYTOTOXIC ACTION OF QUINONIMINES AND alpha-TOCOPHEROL SYNTHETIC DERIVATIVES. AB - The effects of alpha-tocopherol with shortened to 6 carbon atoms side chain (alpha-Toc-C6), alpha-tocopherol succinate (alpha-TS) and quinonimine 2,6 dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. Hepatocytes were least sensitive to the cytotoxic effect of alpha-Toc-C6. In thymocytes and splenocytes alpha-Toc-C6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. Simultaneous induction of cytochrome P450 enzyme expression by alpha-Toc-C6 in hepatocytes is also possible. Cytotoxic effect of alpha-TS does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity. PMID- 26547964 TI - ACTIVITY AND ISOZYME CONTENT OF LACTATE DEHYDROGENASE UNDER LONG-TERM ORAL TAURINE ADMINISTRATION TO RATS. AB - The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190-220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel withfurther staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies. PMID- 26547965 TI - [ACTIVITY OF Ca2+,Mg(2+)-ATPase OF SARCOPLASMIC RETICULUM AND CONTRACTION STRENGTH OF THE FROG SKELETAL MUSCLES UNDER THE EFFECT OF ORGANOPHOSPHORUS INSECTICIDES]. AB - The results of an experimental study of organophosphorus insecticides, including pirimiphosmethyl, diazinon and chlorpyrifos caused a decline of the contraction properties in m. tibialis anterior fiber bundles of Rana temporaria, as well as sarcoplasmic reticulum Ca2+, Mg(2+)-ATPase enzymatic activity reduction are outlined in this paper. Concentration-dependent strengths response diminishing in isolated skeletal muscle fiber bundles as a result of non-cholinergic influence of organophosphorus insecticides were found. A decrease of Ca2+, Mg(2+)-ATPase enzymatic activity in sarcoplasmic reticulum was observed after administration of each insecticide. The most significant inhibition of this enzyme was observed when using chlorpyrifos. PMID- 26547966 TI - REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER. AB - Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr 1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growthfactors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcriptionfactors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P < 0.05) decrease in concentration of protein SH groups in the rat gastric mucosa. These changes were accompanied by significant (P < 0.05) increase in the expression of Egr-1 mRNA and protein in both gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in SpI protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity. PMID- 26547967 TI - [THE ALKALOID-FREE FRACTION FROM Galega officinalis EXTRACT PREVENTS OXIDATIVE STRESS UNDER EXPERIMENTAL DIABETES MELLITUS]. AB - The effect of alkaloid-free fraction from Galega officinalis extract on the process of formation of reactive oxygen species and indicators of prooxidant antioxidant balance was investigated in rat peripheral blood under conditions of experimental diabetes mellitus. It was shown that alkaloid-free fraction from Galega officinalis extract prevents oxidative stress development in rats with streptozotocin-induced diabetes, providing antioxidant and antiradical mobilization mechanisms to protect the blood system. In the case of extract application to animals with studied pathology, one can observe a reducing effect of reactive oxygen species generation in leukocytes, inhibition of proteins and lipids oxidative modification processes and increased activity of key enzymes of rat peripheral blood antioxidant system (superoxide dismutase, catalase and glutathione peroxidase). The revealed biological effect could be explained by the presence of biologically active substances with antioxidant properties in the extract composition (phytol and flavonoids). PMID- 26547968 TI - IDENTIFICATION OF PROTEIN FRACTIONS OF MILK COWS CASEIN COMPLEX. AB - To date, dozens of biologically active peptides formed during proteolysis of casein fractions have been discovered. The use of these peptides is closely related to the necessity of their rapid identification. The aim of this work was the development of an electrophoresis system for rapid identification of individual fractions in serial studies and the separation of the milk casein complex. Considering the abnormal nature of the interaction of caseins with the sodium dodecyl sulfate and similar values of their molecular masses, the anode electrophoresis system in a homogeneous polyacrylamide gel was taken as a basis. Caseins, in this system, are separated according to their charge and located on the electrophoregram in accordance with the modern classification. Urea was used as a disaggregating agent in gel. It was shown that the use of Studier type apparatus for electrophoresis with changeable dimensions of electrophoretic chamber significantly reduces (to 45 min) the time for identification of casein fractions. This method may be useful for rapid identification of casein fractions, as well as for rapid analysis of natural milk and milk products. PMID- 26547969 TI - Invention activity of the Department of Lipid Biochemistry at Palladin Institute of Biochemistry. PMID- 26547970 TI - An effective hybrid approach of gene selection and classification for microarray data based on clustering and particle swarm optimization. AB - In this paper, a hybrid approach based on clustering and Particle Swarm Optimisation (PSO) is proposed to perform gene selection and classification for microarray data. In the new method, firstly, genes are partitioned into a predetermined number of clusters by K-means method. Since the genes in each cluster have much redundancy, Max-Relevance Min-Redundancy (mRMR) strategy is used to reduce redundancy of the clustered genes. Then, PSO is used to perform further gene selection from the remaining clustered genes. Because of its better generalisation performance with much faster convergence rate than other learning algorithms for neural networks, Extreme Learning Machine (ELM) is chosen to evaluate candidate gene subsets selected by PSO and perform samples classification in this study. The proposed method selects less redundant genes as well as increases prediction accuracy and its efficiency and effectiveness are verified by extensive comparisons with other classical methods on three open microarray data. PMID- 26547971 TI - A graph-based integrative method of detecting consistent protein functional modules from multiple data sources. AB - Many clustering methods have been developed to identify functional modules in Protein-Protein Interaction (PPI) networks but the results are far from satisfaction. To overcome the noise and incomplete problems of PPI networks and find more accurate and stable functional modules, we propose an integrative method, bipartite graph-based Non-negative Matrix Factorisation method (BiNMF), in which we adopt multiple biological data sources as different views that describe PPIs. Specifically, traditional clustering models are adopted as preliminary analysis of different views of protein functional similarity. Then the intermediate clustering results are represented by a bipartite graph which can comprehensively represent the relationships between proteins and intermediate clusters and finally overlapping clustering results are achieved. Through extensive experiments, we see that our method is superior to baseline methods and detailed analysis has demonstrated the benefits of integrating diverse clustering methods and multiple biological information sources. PMID- 26547973 TI - Analysing large biological data sets with an improved algorithm for MIC. AB - The computational framework used the traditional similarity measures to find out the significant relationships in biological annotations. But its prerequisites that the biological annotations do not cooccur with each other is particular. To overcome it, in this paper a new method Improved Algorithm for Maximal Information Coefficient (IAMIC) is suggested to discover the hidden regularities between biological annotations. IAMIC approximates a novel similarity coefficient on maximal information coefficient with generality and equitability, by bettering axis partition through quadratic optimisation instead of violence search. The experimental results show that IAMIC is more appropriate for identifying the associations between biological annotations, and further extracting the novel associations hidden in collected data sets than other similarity measures. PMID- 26547972 TI - Exploiting multi-layered vector spaces for signal peptide detection. AB - Analysing and classifying sequences based on similarities and differences is a mathematical problem of escalating relevance and importance in many scientific disciplines. One of the primary challenges in applying machine learning algorithms to sequential data, such as biological sequences, is the extraction and representation of significant features from the data. To address this problem, we have recently developed a representation, entitled Multi-Layered Vector Spaces (MLVS), which is a simple mathematical model that maps sequences into a set of MLVS. We demonstrate the usefulness of the model by applying it to the problem of identifying signal peptides. MLVS feature vectors are generated from a collection of protein sequences and the resulting vectors are used to create support vector machine classifiers. Experiments show that the MLVS-based classifiers are able to outperform or perform on par with several existing methods that are specifically designed for the purpose of identifying signal peptides. PMID- 26547974 TI - miRNA target recognition using features of suboptimal alignments. AB - MicroRNAs (miRNAs) are a class of short RNA molecules that regulate gene expression by binding directly to messenger RNAs. Conventional approaches to miRNA target prediction estimate the accessibility of target sites and the strength of the binding miRNA by finding optimums of some energy models, which involves O(n3) computations. Alternatively, we narrow down potential binding sites of miRNAs to suboptimal hits of a pairwise alignment algorithm called Fitting Alignment in O(n2). We invoke a same algorithm, once for all candidate sites to measure the site accessibilities. These features are applied to a binary classifier being learned to predict true associations between miRNAs and target genes. Training the classifier requires the negative samples indicating non affected genes. The experiments verifying such negative associations have been rarely performed, so we exploit tissue-specific gene expression data to impute the negative associations. The recall rate of our method is above 70% (at precision 85%). PMID- 26547975 TI - Orthogonal projection correction for confounders in biological data classification. AB - The existence of confounders such as population structure in genome-wide association study makes it difficult to apply machine learning methods directly to solve biological problems. It is still unclear how to effectively correct confounders. In this work, we propose an Orthogonal Projection Correction (OPC) method to correct confounders. This is achieved by orthogonally decomposing each feature to a confounding component and a non-confounding component, such that the original data can be best reconstructed by only the non-confounding components of features. The confounder space is built based on prior knowledge, and each feature is projected to its orthogonal complement space. This OPC procedure is shown to be kernelisable. We then propose a ProSVM method by integrating the OPC method and support vector machine for classification. In the experiments, our OPC method for confounder correction improves the tumour diagnosis based on samples from different labs and phenotype prediction in the presence of population structure. PMID- 26547976 TI - Wavelet-based gene selection method for survival prediction in diffuse large B cell lymphomas patients. AB - Microarray technology allows simultaneous measurements of expression levels for thousands of genes. An important aspect of microarray studies includes the prediction of patient survival based on their gene expression profile. This naturally calls for the use of a dimension reduction procedure together with the survival prediction model. In this study, a new method based on wavelet transform for survival-relevant gene selection is presented. Cox proportional hazard model is typically used to build prediction model for patients' survival using the selected genes. The prediction model will be evaluated with the R2, concordance index, likelihood ratio statistic and Akaike information criteria. The results proved that good performance of survival prediction is achieved based on the selected genes. The results suggested the possibility of developing more advanced tools based on wavelets for gene selection from microarray data sets in the context of survival analysis. PMID- 26547978 TI - PMCR-Miner: parallel maximal confident association rules miner algorithm for microarray data set. AB - The MCR-Miner algorithm is aimed to mine all maximal high confident association rules form the microarray up/down-expressed genes data set. This paper introduces two new algorithms: IMCR-Miner and PMCR-Miner. The IMCR-Miner algorithm is an extension of the MCR-Miner algorithm with some improvements. These improvements implement a novel way to store the samples of each gene into a list of unsigned integers in order to benefit using the bitwise operations. In addition, the IMCR Miner algorithm overcomes the drawbacks faced by the MCR-Miner algorithm by setting some restrictions to ignore repeated comparisons. The PMCR-Miner algorithm is a parallel version of the new proposed IMCR-Miner algorithm. The PMCR-Miner algorithm is based on shared-memory systems and task parallelism, where no time is needed in the process of sharing and combining data between processors. The experimental results on real microarray data sets show that the PMCR-Miner algorithm is more efficient and scalable than the counterparts. PMID- 26547977 TI - Sequence based human leukocyte antigen gene prediction using informative physicochemical properties. AB - Prediction of different classes within the human leukocyte antigen (HLA) gene family can provide insight into the human immune system and its response to viral pathogens. Therefore, it is desirable to develop an efficient and easily interpretable method for predicting HLA gene class compared to existing methods. We investigated the HLA gene prediction problem as follows: (a) establishing a dataset (HLA262) such that the sequence identity of the complete HLA dataset was reduced to 30%; (b) proposing a feature set of informative physicochemical properties that cooperate with SVM (named HLAPred) to achieve high accuracy and sensitivity (90.04% and 82.99%, respectively) compared with existing methods; and (c) analysing the informative physicochemical properties to understand the physicochemical properties and molecular mechanisms of the HLA gene family. PMID- 26547979 TI - Cuckoo search optimisation for feature selection in cancer classification: a new approach. AB - Cuckoo Search (CS) optimisation algorithm is used for feature selection in cancer classification using microarray gene expression data. Since the gene expression data has thousands of genes and a small number of samples, feature selection methods can be used for the selection of informative genes to improve the classification accuracy. Initially, the genes are ranked based on T-statistics, Signal-to-Noise Ratio (SNR) and F-statistics values. The CS is used to find the informative genes from the top-m ranked genes. The classification accuracy of k Nearest Neighbour (kNN) technique is used as the fitness function for CS. The proposed method is experimented and analysed with ten different cancer gene expression datasets. The results show that the CS gives 100% average accuracy for DLBCL Harvard, Lung Michigan, Ovarian Cancer, AML-ALL and Lung Harvard2 datasets and it outperforms the existing techniques in DLBCL outcome and prostate datasets. PMID- 26547980 TI - A fast Boyer-Moore type pattern matching algorithm for highly similar sequences. AB - In the last decade, biology and medicine have undergone a fundamental change: next generation sequencing (NGS) technologies have enabled to obtain genomic sequences very quickly and at small costs compared to the traditional Sanger method. These NGS technologies have thus permitted to collect genomic sequences (genes, exomes or even full genomes) of individuals of the same species. These latter sequences are identical to more than 99%. There is thus a strong need for efficient algorithms for indexing and performing fast pattern matching in such specific sets of sequences. In this paper we propose a very efficient algorithm that solves the exact pattern matching problem in a set of highly similar DNA sequences where only the pattern can be pre-processed. This new algorithm extends variants of the Boyer-Moore exact string matching algorithm. Experimental results show that it exhibits the best performances in practice. PMID- 26547981 TI - Towards rule-based metabolic databases: a requirement analysis based on KEGG. AB - Knowledge of metabolic processes is collected in easily accessable online databases which are increasing rapidly in content and detail. Using these databases for the automatic construction of metabolic network models requires high accuracy and consistency. In this bipartite study we evaluate current accuracy and consistency problems using the KEGG database as a prominent example and propose design principles for dealing with such problems. In the first half, we present our computational approach for classifying inconsistencies and provide an overview of the classes of inconsistencies we identified. We detected inconsistencies both for database entries referring to substances and entries referring to reactions. In the second part, we present strategies to deal with the detected problem classes. We especially propose a rule-based database approach which allows for the inclusion of parameterised molecular species and parameterised reactions. Detailed case-studies and a comparison of explicit networks from KEGG with their anticipated rule-based representation underline the applicability and scalability of this approach. PMID- 26547982 TI - In silico identification and functional annotation of yeast E3 ubiquitin ligase Rsp5 substrates. AB - Rsp5, E3 ligases conserved from yeast to mammals, plays a key role in diverse processes in yeast. However, many of Rsp5 substrates are still unclear. Therefore we proposed an in silico method to recognise new substrates of Rsp5. To investigate the molecular determinants that affect the interaction between Rsp5 and its substrate, we have systematically analysed many features that perhaps correlated with the Rsp5 substrate recognition. It is found that PPxY motif, transmembrane region, disorder region and N-linked glycosylation modification are the most important features for substrate recognition. We have constructed an SVM based classifier to recognise Rsp5 substrates, obtaining 81.5% sensitivity and 74.1% specificity averagely on ten independent testing dataset. We also applied the model on the whole yeast proteome, and identified -66 new Rsp5 substrates. Functional annotation reveals that half of these novel substrates function in the Rsp5 involved cell processes as Rsp5-interacting proteins. PMID- 26547983 TI - Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression. AB - In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods. In addition, the sequence-folding step is addressed by investigating the impact of secondary structure prediction methods and the choice of input sequence length on prediction performance. Both the accuracy of secondary structure predictions and the miRNA prediction are evaluated. In the benchmark of hairpin classification methods, the regression model achieved highest classification accuracy. Of the structure prediction methods evaluated, ContextFold achieved the highest agreement between predicted and experimentally determined structures. However, both the choice of secondary structure prediction method and input sequence length had limited impact on hairpin classification performance. PMID- 26547984 TI - Application of consensus string matching in the diagnosis of allelic heterogeneity involving transposition mutation. AB - In this paper, an algorithm is proposed that detects the existence of a common ancestor gene sequence for non-overlapping transposition metric given two input DNA sequences. We consider two cases: fixed length transposition and all length transposition. For the first one, the algorithm has the time complexity of O(n3), where n is the length of input sequences. In case of all length transposition, theoretical worst case time complexity of the algorithm is proven to be O(n4). However, practically the worst case and the average case time complexity for all length transposition are found to be O(n3) and O(n2) respectively. This work is motivated by the purpose of diagnosing unknown genetic disease that shows allelic heterogeneity, a case where a normal gene mutates in different orders resulting in two different gene sequences causing two different genetic diseases. The algorithm can be useful as well in the study of breed-related hereditary to determine the genetic spread of a defective gene in the population. PMID- 26547985 TI - Weighted fusion regularisation and predicting microbial interactions with vector autoregressive model. AB - In this paper, we develop a novel regularisation method for MVAR via weighted fusion which considers the correlation among variables. In theory, we discuss the grouping effect of weighted fusion regularisation for linear models. By virtue of the probability method, we show that coefficients corresponding to highly correlated predictors have small differences. A quantitative estimate for such small differences is given regardless of the coefficients signs. The estimate is also improved when consider empirical approximation error if the model fit the data well. We then apply the proposed model on several time series data sets especially a time series dataset of human gut microbiomes. The experimental results indicate that the new approach has better performance than several other VAR-based models and we also demonstrate its capability of extracting relevant microbial interactions. PMID- 26547986 TI - Learning multiple distributed prototypes of semantic categories for named entity recognition. AB - The scarcity of large labelled datasets comprising clinical text that can be exploited within the paradigm of supervised machine learning creates barriers for the secondary use of data from electronic health records. It is therefore important to develop capabilities to leverage the large amounts of unlabelled data that, indeed, tend to be readily available. One technique utilises distributional semantics to create word representations in a wholly unsupervised manner and uses existing training data to learn prototypical representations of predefined semantic categories. Features describing whether a given word belongs to a certain category are then provided to the learning algorithm. It has been shown that using multiple distributional semantic models, each employing a different word order strategy, can lead to enhanced predictive performance. Here, another hyperparameter is also varied--the size of the context window--and an experimental investigation shows that this leads to further performance gains. PMID- 26547987 TI - Looking forward, reflecting back. PMID- 26547988 TI - Let's make our maternity services excellent! PMID- 26547989 TI - New guidance to foster openness and honesty. PMID- 26547990 TI - Initiatives highlight extent of FGM in UK. PMID- 26547991 TI - When early and often counts. AB - In 2000, Millennium Development Goal 4 called for global deaths in under fives, to be reduced by two thirds by 2015 (United Nations Millennium Declaration (UNMD) 2000). Birth asphyxia - failure to initiate or sustain spontaneous breathing at birth - causes up to one million neonatal deaths per year (Ersdal and Singhal 2013). A high proportion.of these are in low-resource countries. In 2009, a group of doctors and academics from hospitals and universities in Norway and the United States wanted to find out if the Helping babies breathe (HBB) simulation-based programme for midwives in low-resource countries helped reduce newborn fatalities in a hospital in Tanzania. I was one of those doctors and our research showed that when teaching switched from a one-day programme to a low-dose, high frequency model, emphasising immediate basic steps, there was a significant increase in the number of infants stimulated at birth, and a 40 per cent decrease in early neonatal mortality. PMID- 26547992 TI - The power of two: reflections on the MBRRACE-UK maternal and perinatal deaths reports and the London maternity strategic clinical network. AB - The UK maternal mortality rate is 10 per 100,000-maternities and is falling. The decrease is due to fewer deaths from direct causes; there has been no significant change in the indirect rate over the last 10 years. The UK mortality rate for babies is six stillbirths and neonatal deaths per 100,000 births. Local rates vary from 5.4-7.1. The variation is not due to normal variation or demographic factors. The London Maternity Strategic Clinical Network uses a multi disciplinary team approach to improve maternity user experience. The Northern New England Cardiovascular Disease Study Group (NNE CVDSG) meet to share data, observe clinical practice and make changes. Maternity units may wish to consider adapting the NNE CVDSG approach to improve their quality of maternity care. PMID- 26547993 TI - Making it happen: a programme of education in Kenya. AB - The number of mothers and babies from the developing world who die in pregnancy and childbirth remains unacceptably high. However, concerted efforts over the last 20 years to reduce the number of deaths have produced significant results, leading to a steady fall in maternal and neonatal mortality rates since 1990 (Unicef 2014). One initiative that is having an impact is the 'Making it happen' programme funded by the UK government and run by Liverpool's School of Tropical Medicine. A 'skills and drills'-type course covering obstetric and neonatal emergencies is delivered to health professionals across Sub-Saharan Africa and Asia. This article describes the volunteer experience of a UK midwife helping to facilitate a course in Kenya, which has some of the world's poorest health outcomes. PMID- 26547994 TI - The 'art' of successful breastfeeding education. AB - Breastfeeding education must motivate a complete workforce in such a way that they are equipped with the fundamentals and extended skills to carry out their role as infant feeding gurus, throughout their career. To achieve this with any success, there is an intrinsic need to establish a total understanding of both the physiology and emotional importance which underlies the art of breastfeeding. Only when this is attained will passion and longevity for the 'art' be fully embraced and respected. PMID- 26547995 TI - Midwives making a difference: a conference organised by and for student midwives. AB - The midwifery council at Bournemouth University, each year, is set the objective to organise and deliver a conference for student midwives. It is a very lengthy task that requires a lot of dedication from the students who make up the council; they work tirelessly to arrange speakers for the day. Previous speakers at the conferences have included Michel Odent, Milli Hill and representatives from charities. Although time consuming, the day is highly valued by the students and it equips each council member with organisational, public-speaking and time management skills that are essential for midwifery practice today. PMID- 26547996 TI - Towards midwifery education and regulation in Nepal. AB - This is a short reflection of four wonderful weeks spent in Nepal supporting, advocating and strengthening the existing work of the Midwifery Society of Nepal and the Global midwifery twinning project (GMTP) with the Royal College of Midwives. Although Nepal is on target to achieve reduction in its maternal mortality rate for millennium goal 5 there is still no registered protected title of 'midwife' In order to establish a strong midwifery workforce in Nepal, the three pillars that need to be highlighted are: midwifery education, midwifery regulation and professional midwifery association. The four-week programme led by GMTP volunteers helped towards building capacity in leadership, advocacy and campaigning skills in Nepal. PMID- 26547997 TI - Introducing educational theory: vaginal examination. AB - A vaginal examination (VE) is one of many core skills used in midwifery practice. Despite the controversy of whether it is necessary in all situations, in this article I take the standpoint that it is useful in providing a full clinical picture, especially at times when closer monitoring is recommended. Additionally, if the core skill is misinterpreted, the findings of the VE can distort the true clinical picture. To support the student, subjective assessment and individual learning pathways must be addressed to avoid unnecessary intervention and psychological impairment to the woman. This article explores some of the difficulties encountered with teaching and learning VE in clinical practice and offers concepts from educational theory to assist in clarifying the difficulties and offering new ways of thinking for both students and midwives. PMID- 26547998 TI - To be a midwife: overcoming the obstacles in Canada (part 2). AB - This two-part article introduces my working background in grassroots Canadian midwifery, and my subsequent shift into 'thinking birth' through what I call the 'philosopher-midwife' I broach the idea that midwifery is a site of not only holistic birth care, but of woman-centred birth studies and enquiry. Part 1 conveyed a storied account of my working background in midwifery care, situated in the re-emergence of North American midwifery. I discussed how midwifery is a relational, woman-centred method of knowing and enquiry. I have come to understand midwifery as a metaphor for attending to the gift of life, a woman centred way of healing, and an ongoing practice of overcoming oppositional circumstances. Part 2 introduces ideas on how birth, in concept and experience, has not been adequately addressed in social philosophy and understanding. I suggest this be remedied through attention to midwives' and women's birth experiences. In this attention, I muse on how the 'philosopher-midwife' may further guide new birth-based enquiries. PMID- 26547999 TI - Why won't Polish women birth at home? AB - Polish women living in the United Kingdom (UK) are statistically more likely to have normal births than their British counterparts, yet anecdotally, do not choose to birth their babies at home. A medicalised approach to birth in their country of origin means women are unaware of the benefits of midwifery-led care, which they often perceive as sub-standard. Affordable travel means Polish women can access care in both countries and compounds the difficulties in acclimatising to UK maternity services. Online discussion groups and Internet forums represent an opportunity for midwives to engage with women to promote their services. This is increasingly important with rising numbers of both Polish migrants to the UK and Polish residents applying for British citizenship. PMID- 26548000 TI - How are you sleeping? PMID- 26548001 TI - Herophilus. PMID- 26548002 TI - [Customers are entitled to quick and comprehensible decisions]. PMID- 26548003 TI - [Update rheumatism focusing on rheumatoid arthritis]. AB - Rheumatic diseases do not only represent a challenge in day to day clinical medicine but also during underwriting and claims handling in insurance medicine. New diagnostic laboratory tests and therapeutic options constantly improve diagnostic quality and treatment outcomes. Using rheumatoid arthritis (RA) as an example this article explains how this new aspects found their way into international diagnostic criteria and treatment guidelines. The introduction of diagnostic ACPAs (Anti-Citrullinated Protein Antibodies) and the therapeutic use of currently still relatively expensive biologicals have to be highlighted in this respect. Backed by modern therapeutic options recent RA morbidity figures of employed persons indicate a shift to less severe morbidity spectra. For individual case evaluation it is of importance to understand the most relevant aspects of such innovations for adequate and sound case assessment in underwriting and claims. PMID- 26548004 TI - [Patients' rights - medical duties (II). An analysis of the patients' rights law by physicians for physicians]. PMID- 26548005 TI - [Principles of intervertebral disc assessment in private accident insurance]. AB - Due to the spread of intervertebral disc degeneration, insurance companies and experts are regularly confronted with related assessments of insured persons under their private accident insurance. These claims pose a particular challenge for experts, since, in addition to the clinical assessment of the facts, extensive knowledge of general accident insurance conditions, case law and current study findings is required. Each case can only be properly assessed through simultaneous consideration of both the medical and legal facts. These guidelines serve as the basis for experts and claims.managers with respect to the appropriate individual factual assessment of intervertebral disc degeneration in private accident insurance. PMID- 26548006 TI - [Ambient assisted living - an overview]. AB - Ambient assisted living (AAL) technologies are mainly developed to support elderly people in their own homes and facilitate a longer, self-determined life. In addition to providing a demographic prognosis for Germany, the present publication includes the definition, classification and current market situation of AAL. Lastly, the benefit of AAL technologies to the insurance industry and the subsequent steps to be taken are addressed. PMID- 26548007 TI - [Telemedicine - an overview]. AB - Currently, there is considerable interest in telemedicine for two reasons: Firstly, it is expected to bring improvements in health care. Secondly, it is assumed that telemedicine reduces health care costs. The latter is of particular importance because health care costs are expected to rise considerably in the future. The present article describes the current situation of telemedicine in Germany. PMID- 26548008 TI - [Insurance medicine - an overview from the Swiss perspective]. AB - Since the middle of the 19th century insurance medicine has played a role in medical risk assessment and underwriting for insurance applications, and since the beginning of the 20th century medical professionals have been assisting social insurance institutions with claims adjustments. However, insurance medicine has not yet become firmly established within the medical community. This may to a large extent be related to the fact that insurance medicine is not in itself curative and therefore tends to be sidelined by clinical subjects, while little or no teaching time is dedicated to the topic during basic and advanced training. A few institutions do offer training on the topic, although this is generally limited to the respective arrangements for claims and risk assessment. These factors result in insurance medicine being treated as a fragmented subject with no clear or consistent definitions, leaving it devoid of identity. This article begins by tracing the broad outlines of the history of insurance medicine, before offering a comprehensive definition and description of insurance medicine and providing information on the existing training opportunities and institutions concerned with insurance medicine. PMID- 26548009 TI - [Is a pre-contractual secretive multiple sclerosis, even after the 10 tear BU contract period, still legally sanctionable?]. PMID- 26548010 TI - [Fascinating TCM]. PMID- 26548011 TI - [Unexpected serious illness in the travel cancellation insurance]. PMID- 26548012 TI - [Alternative medicine treatment of metastatic malignant melanoma]. PMID- 26548013 TI - [Biomarkers for the diagnosis of fatigue in patients with multiple sclerosis]. PMID- 26548014 TI - [Letter to A. Boger : Complex regional pain syndrome ( CRPS ) - difficulties in the diagnosis, treatment and evaluation in Insurance Medicine 67 ( 2015) Issue 1 , page . 9]. PMID- 26548015 TI - [Medical Insurance . 2015 Mar 1 ; 67 ( 1 ) : 9-12]. PMID- 26548016 TI - [Suicide among physicians--a current analysis for the City of Hamburg]. AB - According to the literature, physicians have an increased risk of committing suicide, which can partly be explained by occupational stress. A retrospective analysis of the deaths investigated by the Hamburg office of Criminal Investigation and documents of the Hamburg Institute of Forensic Medicine for the years 2001 to 2013 showed that the average suicide rate among physicians is not significantly higher than that of the total population, it is 0.021% for physicians, 0.023% for dentists and 0.013% for the general public; thus the difference is not statistically significant (p: 0.57 for physicians and 0.74 for dentists). Drug intoxication has been found to be the most common method of suicide committed by physicians. However, these results must be interpreted with caution in view of the fact that a detailed evaluation of data was often not possible, especially because information as to the profession of the deceased and the motive for the suicide were missing or insufficiently documented. PMID- 26548017 TI - [Morphology and phenomenology of crossbow injuries with a review of the literature]. AB - This paper presents two cases of survived and fatal injuries caused by broad-head arrows. Case no. 1 is characterised by repeated assaults resulting in severe injuries to the legs of the victim. The lesions showed characteristic patterns due to the arrow-heads with four cross-shaped blades. Case no. 2 represented a suicide with the crossbow arrow entering the upper mouth region at close range, penetrating the base of the skull, the pons and the inter-hemispheric space, with the tip of the arrow being lodged in the skullcap. Morphology of the wounds, ballistic features and technical characteristics are discussed and the available literature is reviewed. PMID- 26548018 TI - [Corpse disposal by concealment in transport containers or packaging materials: Examination by post-mortem computed tomography (PMCT) before forensic autopsy]. AB - The presented case reports illustrate the value of post-mortem computed tomography in cases of homicide in which the body was hidden in a container or packaging material and could not be inspected directly from outside. In Case 1, the body was forced into a suitcase, which was then thrown into a flood basin. Post-mortem computed tomography (PMCT) visualized the compressed and extremely flexed body inside the suitcase as well as fractures of the left temporal bone, the left ulna and the left side of the mandible. After recovery of the body, the consequences of long-term immersion in fresh water became visible. At autopsy, a laceration in the left temporal region and a temporal bone fracture were observed. The fractures of the left ulna and the left jaw were associated with moderate hematoma. In Case 2, the body of an 11-year-old girl was retrieved from a plastic bag concealed in a garden shed. The cause of death was ligature strangulation. In the presented cases, PMCT was performed as part of the police investigations for reliable primary documentation of the contents of the containers without further manipulation. Thus the human body, its position inside the container and the presence of bone injuries could be demonstrated before opening the container. In such cases, post-mortem imaging provides reliable and rapid information to the investigating authorities before autopsy already. PMID- 26548019 TI - [Death by explosion of an aerial mine]. AB - Civilians are rarely killed by military weapons except in times of war. In early 2014, a 50-year-old man died in an explosion of an aerial mine from the Second World War when he was crushing concrete chunks with an excavator at a recycling plant. In the burned operator's cab, the remains of a body were found on the driver's seat. The thorax and the head were missing. Still sticking in the shoe, the right foot severed at the ankle was found about 7 m from the excavator together with numerous small to tiny body parts. At autopsy, the completely disrupted, strongly charred lower torso of a male connected to the left extremities as well as a large number of small tissue fragments and calcined bones were found. According to calculations performed by the seismographical station on the basis of seismic data, only about 45-60 percent of the charge had detonated. The autopsy results illustrate all the more the massive impact of such an explosion. PMID- 26548020 TI - [Myiasis because of neglect]. AB - Myiasis is known as the infestation of living organisms with maggots. It is often caused by (self-) neglect. Eight cases of myiasis have been examined at the Institute of Legal Medicine in Hamburg between 2002 and 2014. It is important that the medical examiner compares the maggots' stage of development with the alleged time of death. Especially in cases of home care, myiasis and neglect are suspicious and deserve special attention. PMID- 26548021 TI - [Alleged assault in a forest: An unusual case of self-inflicted blunt injury]. AB - The medico-legal assessment of potentially self-inflicted injuries is an important field of clinical forensic medicine. Compared with sharp force injuries, it is much more difficult to distinguish blunt injuries caused by another party from self-inflicted lesions. We present a case of a young female doctor, who was allegedly attacked by an unknown stranger during her evening walk in the woods. She claimed to have been hit repeatedly on the head and arms with a stone. During the forensic investigation, blunt injuries could be confirmed on her head and forearms. Based on the arrangement and intensity of the injuries, together with the result of a bloodstain pattern analysis of the weapon, the victim's statement could be disproved. After being confronted with the results of the investigation, the woman admitted to have inflicted the injuries herself. This case is an unusual and rare example of self-inflicted blunt injury. It shows that the criteria of self-inflicted injuries can also be applied to blunt trauma. However, due to the small number of cases, a high degree of caution is required from the forensic expert. PMID- 26548022 TI - [[Medico-historical findings of (neuro-) prosthetics: an online survey]. AB - This article presents an online survey on medico-historical (neuro-)prostheses. Important findings of the past 3000 years are outlined: toe prostheses from ancient Egypt, the Capua leg prosthesis, Gotz von Berlichingen's artificial hands and Sauerbruch's prosthetic arm. These historical examples are compared with modern neuroprosthetics. It is also shown that historical prostheses were in no way primitive and, even more, that ancient people already used first intelligent medical engineering approaches. PMID- 26548023 TI - [Walcher's hat brim line rule--a literature review]. AB - The first description in the forensic medical literature of a demarcation line for the localization of head injuries resulting from falling to the ground appears in Kratter (1919). Regarding a similar line, Walcher (1931) later introduced the relation to the hat brim (Hutkrempe), which gave the rule its name: the hat brim line rule (Hutkrempenregel). Thenceforth it was supposed to be called Kratter's and Walcher's hat brim line rule (Kratter-Walcher'sche Hutkrempenregel). Over the following decades, not only its content but also the area of application and the definition of the hat brim line rule were repeatedly, and in part significantly, altered. This could be one of the reasons for the confusing diversity of academic opinions about the rule's applicability. Generally, the hat brim line rule should be retained in its original sense: Fall related injuries do not lie above the hat brim line if the fall occurred from a standing position to the ground, without intermediary blows to the head. If applied in this way, the rule can be a helpful point of orientation for experts. The demarcation line in the original anatomical definition according to Kratter (1919) should also be used henceforth: the line which connects "the frontal eminence, the parietal eminence and the tip of the occipital plate" and lies "somewhat.above the usual saw-line of the calvarium". This line corresponds roughly to the hat brim line as it is understood by hat makers. The hat brim line rule should not be applied with regard to small children, as they show a different falling behaviour due to their disproportionately large and heavy heads. The rule is also in no way applicable to the assessment of injuries from blows, falls from a height (including from stairs) or traffic accidents. There is an urgent need for research as to the applicability of the hat brim line rule in relation to falling backwards, particularly in cases of high alcohol consumption. PMID- 26548024 TI - [Semi-structured interviews on suicidality in the Hamburg pre-trial detention center]. AB - A detailed study regarding inmates' suicides was conducted in the detention center of Holstenglacis Hamburg (UHA). This study was triggered by an above average number of attempted and committed suicides in detention centers in Germany and in particular, two committed suicides in the above-mentioned prison in early 2012. In this qualitative empirical study, 20 semi-structured interviews were conducted with inmates and staff of the UHA Hamburg. The focus was placed on aspects encountered in the daily life within the detention center and stressful situations that could encourage suicides. This article presents the most striking results of the study which are used as a basis for proposing several preventative measures. The aim of this article is to present new ideas and methods conducive to a decrease in the number of suicides in detention centers at minimal costs and personnel expenses. PMID- 26548025 TI - [Use of sonography in splinter injuries: a model simulation]. AB - In many clinical disciplines and in forensics, non-visible splinter injuries are still a diagnostic challenge. In clinical routine, this kind of injury is diagnosed by radiography whereas ultrasound has not yet been applied for this indication. We, therefore, investigated the role of ultrasound in the detection of splinters by using gelatine and meat models. Splinters were from wood, roses, plastics, metal, and glass. All splinters were easily detectable by ultrasound. The ultrasound models were compared with X-ray images and, in the case of a rose thorn scarcely visible in the conventional X-ray image, with a CT scan. As demonstrated by the promising results of this simulation, ultrasound may be a significant improvement for in vivo and post mortem diagnostics of splinter injuries as compared to conventional X-ray imaging. PMID- 26548026 TI - [Corpse disposal by embedding it in concrete--a rare form of preserving a body over a period of 5 years and 10 months]. AB - Final disposal of a homicide victim in concrete is rare. Often missing persons are reported to the police, but the right of adults to determine their whereabouts can make it very difficult to locate them. A 40-year-old woman had been missing for 5 years and 10 months. She was found by the police in the cellar of the family's house, packed in airtight plastic film and embedded in concrete. The husband admitted to have killed her by manual strangulation after an argument during which she fell on the head. His statements were confirmed by the findings obtained from the very well preserved body. The autopsy results were generally consistent with manual strangulation. The literature does not contain many case reports on this rare method of disposing of a body. In the reported case, the postmortem period was remarkably long and the corpse was in a good state of preservation. PMID- 26548027 TI - [Conventional radiology versus the increasing importance of post-mortem computed tomography]. AB - Radiological imaging can provide valuable additional information, facilitate and improve the quality of subsequent autopsy. Although the use of cross-sectional imaging methods is increasing, they are not always available in medico-legal practice. In many cases it is advisable to perform conventional X-rays before autopsy, especially in cases of gunshot injuries, as illustrated by a case in which the victim suffered several gunshot wounds with one projectile lodged in a vertebral body. The radiological findings essentially contributed to the rapid location of the projectiles and the reconstruction of the bullet paths. PMID- 26548028 TI - Insulin Degludec/Insulin Aspart: A Novel Co-formulation for Insulin Intensification. PMID- 26548029 TI - Intensifying Insulin Therapy in Type 2 Diabetes: Choices & Challenges. AB - Insulin therapy remains the cornerstone of effective diabetes management. Timely intensification of insulin therapy reduces the progression of diabetes and the development of diabetes-related complications. Given that overall hyperglycaemia is a relative contribution of both fasting and postprandial hyperglycaemia, use of basal insulin alone may not achieve optimal glucose control due to its inability to cover postprandial glucose excursions. Intensifying therapy with addition of bolus insulin or switching to premixed insulin is a viable option in patients failing on basal alone therapy. Although the benefits of early insulin treatment are well established, a considerable delay in intensifying insulin therapy in patients with sub-optimal glycaemic control is still observed. Most of the patients and physicians are reluctant to intensify therapy due to the fear of hypoglycaemia, regimen complexity, and increased burden of multiple daily injections. In this context, there is a need for a flexible, alternative intensification option taking into account individual patient considerations to achieve or maintain individual glycaemic targets. An ideal insulin regimen should mimic physiological insulin release while providing optimal glycaemic control with low risk of hypoglycaemia, weight gain and fewer daily injections. The current paper reviews the challenges of insulin intensification in patients with type 2 diabetes mellitus poorly controlled on current treatment regimens. PMID- 26548030 TI - Review of Clinical Profile of IDegAsp. AB - In patients with diabetes, treatment intensification requires basal and bolus insulin injections to control the fasting and prandial insulin needs. To overcome the burden of multiple daily injections, co-formulating basal and bolus insulins in single injection could allow a simple regimen with fewer injections. Current premixed insulin analogues are limited by the protaminated insulin component, which cannot provide effective basal coverage. While, long-acting insulin analogues like insulin glargine and insulin detemir cannot be combined with rapid acting insulin analogues due to physicochemical incompatibility. Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of two distinct insulin analogues in the ratio of 70% ultra-long-acting insulin degludec (IDeg) and 30% rapid-acting insulin aspart (IAsp). The distinct PK/PD properties of IDeg and IAsp components are preserved in the co-formulation, with the rapid absorption characteristics of IAsp and flat and stable profile of IDeg maintained separately. Size exclusion chromatography studies of IDegAsp indicate that IDeg and lAsp exist as stable di-hexamers and hexamers, respectively in the formulation. Moreover, at steady state, the prandial and basal glucose lowering effects of IDeg and IAsp were distinct and clearly separated. A clear dose response relationship was observed in patients with type 1 and type 2 diabetes treated with IDegAsp. The glucose lowering effects of basal and prandial components of IDegAsp are maintained in elderly (>= 65 years of age) patients with type 1 diabetes. In addition, the PK and clearance of IDeg and IAsp are not affected by mild, moderate or severe renal or hepatic impairment. Presence of two distinct insulin analogues, as a soluble co-formulation with basal component with an ultra-long duration of action makes IDegAsp an advance to premix insulins. PMID- 26548031 TI - Overview of Clinical Trial Program and Applicability of Insulin Degludec/Insulin Aspart in Diabetes Management. AB - Insulin degludec/insulin aspart (IDegAsp) is the first soluble coformulation combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In patients with uncontrolled type 2 diabetes (T2DM) previously treated with insulins, IDegAsp twice daily effectively improves glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels with fewer hypoglycaemic episodes versus premix insulins. Further, insulin initiation with IDegAsp once daily provides superior long-term glycaemic control compared to insulin glargine with similar FPG and insulin doses, and numerically lower rates of overall and nocturnal hypoglycaemia. In patients with type 1 diabetes mellitus (T1DM), IDegAsp once daily and IAsp at remaining meals provides more convenient three injection regimen per day over conventional 4-5 injections based basal-bolus therapy. IDegAsp is an appropriate and reasonable option for intensifying insulin therapy in patients with T2DM and a relatively less complex treatment option for the management of T1DM. PMID- 26548032 TI - [Fire disaster due to deflagration of a propane gas-air mixture]. AB - On 26 Nov 2012, a serious fire occurred at Neustadt/Black Forest in which 14 persons in a sheltered workshop died and 10 other individuals were injured. The fire was caused by the unbridled escape of propane gas due to accidental disconnection of the screw fixing between a gas bottle and a catalytic heater. Deflagration of the propane gas-air mixture set the workshop facilities on fire. In spite of partly extensive burns the fatally injured victims could be rapidly identified. The results of the fire investigations at the scene and the autopsy findings are presented. Carboxyhemoglobin concentrations ranged between 8 and 56 % and signs of fire fume inhalation were present in all cases. Three victims had eardrum ruptures due to the sudden increase in air pressure during the deflagration. PMID- 26548033 TI - [On the forensic relevance of orphan diseases]. AB - A 40-year-old woman died shortly after complaining of non-specific symptoms after a pharmacist had accidentally given her the wrong medication. The woman's partner was not familiar with her medical history and the medical file had to be obtained from the family doctor. Autopsy findings and histological examination confirmed the clinically diagnosed autoimmune polyglandular syndrome without a tangible cause of death. Poisoning could not be demonstrated and no relation between the dosage error and death could be established. Laboratory tests revealed diabetic coma with ketoacidosis as the cause of death, which was probably caused by a prolonged lack of insulin administration. In addition to the clarification of legal issues, the complete post-mortem examination of orphan diseases is also relevant for achieving a better understanding of differential diagnostic aspects and complex pathophysiological contexts. Moreover, the genetic background often underlying such diseases should be a reason to inform the family of the deceased about the autopsy results. Only then can secondary preventive measures be taken in time. PMID- 26548034 TI - [Lethal intravenous injection of benzine]. AB - A man who suffered from chronic pain syndrome died two days after intravenous injection of 2 ml benzine. Previous suicide attempts by drug intoxication and strangulation had failed. Death occurred due to multi-organ failure. We present the results of the clinical, morphological and toxicological examinations performed. PMID- 26548035 TI - [Death by alcoholic ketoacidosis--analytical procedure and case report]. AB - Alcoholic ketoacidosis is a medical emergency, which is characterized at first by an elevated level of ketone bodies. The production of these ketone bodies is accompanied by an equimolar quantity of hydrogen ions and thus causes acidosis, which cannot be detected post-mortem due to anaerobic glycolysis, whereas the three ketone bodies beta-hydroxybutyrate, acetoacetate and acetone can be easily identified. However, the limits of ketone body concentrations mentioned in the literature for diagnosing ketoacidosis vary significantly, partly due to inhomogeneous study groups. A 44-year-old woman was found dead with numerous haematomas and partial mummification. Some days before, she had reported her partner to the police for rape. Consequently investigations for homicide were initiated. The autopsy itself did not reveal any morphologically identifiable cause of death. The ketone body concentrations in three matrices (vitreous humour, cerebrospinal fluid, cardiac blood) left no doubt that death was due to alcoholic ketoacidosis. PMID- 26548036 TI - [Death by avalanche in the minor mountain range]. AB - On 30 Jan 2015, two avalanche accidents happened in the Black Forest (at the foot of the 1493 m high Feldberg and the Herzogenhorn situated next to it), in which experienced ski tourers--a 58-year-old woman and a 20-year-old man--were completely buried by snow masses. Both victims were recovered dead after nearly 2 hours under the snow. The avalanches were promoted by strong snowfalls, snowdrift by the wind and steep downwind slopes. One of the victims, the 20-year-old man, underwent a forensic autopsy. The findings suggested death by protracted asphyxiation with agonal hypothermia. A mechanical traumatization with internal injuries suspected by the emergency doctor at the scene could not be confirmed at autopsy. The possible causes of death in the avalanche are discussed using the reported case as an example and in reference to the relevant literature. PMID- 26548037 TI - [Suicidal fall from height after restraint or accident?]. AB - Restraining patients is common practice in psychiatric hospitals and is permitted by section 1906 BGB (German Civil Code) if there is a risk of suicide or serious self-damage because of a mental disease or mental disability. Permanent monitoring and supervision during restraints should be obligatory not only in psychiatric hospitals. Nevertheless a number of deaths have occurred during restraints, usually due to strangulation. Reports of cases with suicidal actions after self-release from restraint are rare in the literature. We report on the case of a 45-year-old woman who had suffered from schizophrenia for more than 20 years. After admission to a hospital, she had to be restrained since she became more and more aggressive. When the monitor showed no vital signs any more, nurses checked the patient's room and found an empty bed. The woman was detected lying on the ground in a pool of blood under an open window of the hospital. The cause of death was a polytrauma with leading cranio-cerebral injuries. Obviously the woman had freed herself from the restraining device and committed suicide by jumping out of the window on the third floor. PMID- 26548039 TI - Partnering expertise with experience. PMID- 26548038 TI - [Commemoration ceremony for 100th anniversary of the death of Hans Gross (1847 1915)]. PMID- 26548040 TI - Recent night shift pushes enrolled nurse to the limits. PMID- 26548041 TI - Neglecting democratic rights. PMID- 26548042 TI - Don't segregate young nurses. PMID- 26548043 TI - Disappointed with cover. PMID- 26548044 TI - Cover shows poor practice. PMID- 26548045 TI - Letting nursing down. PMID- 26548046 TI - Appearance plays a role. PMID- 26548047 TI - Presenting professionally. PMID- 26548048 TI - Doing nurses an injustice. PMID- 26548049 TI - Co-editors respond. PMID- 26548050 TI - The charge nurse manager of Wellington Hospital's ICU, Stephen James, responds. PMID- 26548052 TI - Rehashing conspiracy theories. PMID- 26548051 TI - Please look at the science. PMID- 26548053 TI - Science improves quality of life. PMID- 26548054 TI - Letter full of inaccuracies. PMID- 26548055 TI - Remembering Betty Dunn. PMID- 26548056 TI - The President comments. PMID- 26548057 TI - Social media drives 'intense' campaign. PMID- 26548058 TI - Equal pay pressure mounts. PMID- 26548059 TI - DHB MECA ratified. PMID- 26548060 TI - Unions in mediation over masks. PMID- 26548061 TI - 'Flawed' health and safety bill passed. PMID- 26548062 TI - The mutual benefits of preceptorship. PMID- 26548064 TI - What's wrong with social bonds in mental health? PMID- 26548063 TI - Trained actors help students learn mental health nursing skills. PMID- 26548065 TI - Driving out systemic discrimination. PMID- 26548066 TI - Weaving mental health into WITT's undergraduate curriculum. PMID- 26548067 TI - Clinical reasoning tool aids practice. PMID- 26548068 TI - 'Whole person' approach used in complex TB case. PMID- 26548069 TI - Mental health triage--what Skills are needed? PMID- 26548070 TI - Unmasking managerial power. PMID- 26548071 TI - Providing immunisation across the lifespan. PMID- 26548072 TI - Transcribing medications. PMID- 26548074 TI - As time goes by... PMID- 26548073 TI - Primary health care: Heartfelt messages. PMID- 26548075 TI - Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development. AB - The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed. PMID- 26548076 TI - Thalamic superoxide and peroxide handling capacity (SPHC): An experimental study with aluminum, ethanol and tocopherol in rats. AB - Superoxide and peroxide handling capacity (SPHC) is an important determinant of oxidative stress. Neurotoxic impacts of aluminum are associated with oxidant imbalance. Here, we studied the influence of aluminum on oxidative stress parameters, antioxidative enzymes and SPHC of thalamic area on pro-oxidant (ethanol) and antioxidant (alpha-tocopherol) exposure. Two sets of male Wistar rats were divided into 8 groups (6 each) and exposed to aluminum (10 mg/Kg body wt.), ethanol (0.6 g/Kg body wt.) and alpha-tocopherol (5 IU/day) for 4 wk, each having respective control group. Levels of reduced glutathione (GSH), lipid peroxidation (TBARS) along with activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) of thalamic area were estimated for each group. Glutathione-independent superoxide peroxide handling capacity (GI-SPHC) and glutathione-dependent superoxide peroxide handling capacity (GD-SPHC) were calculated from the GPx, CAT and SOD values. Concomitant exposure to aluminum and ethanol demonstrated significant increase in SOD activity and significant decrease in GPx activity compared to the control group, while lone aluminum-exposed rats showed raised GR activity, without alterations in GPx and SOD activities. However, significant reduction of both GI- and GD- SPHC were found in ethanol-exposed groups. alpha-Tocopherol supplementation could resist most of the alterations. In addition, current antioxidant exposure reduced the inherent GD-SPHC, and thus, made thalamic area more vulnerable to oxidant threat. The present study corroborates the thalamic susceptibility to aluminum-augmented oxidant imbalance and suggests cautious use of antioxidant supplementation against neurodegenerative disorders. PMID- 26548077 TI - Ginger extract ameliorates phosphamidon induced hepatotoxicity. AB - Organophosphorus (OP) compounds commonly used as pesticides in agriculture cause serious health problems to living beings. The present study enumerates the ameliorating effect of ginger extract (GE) against phosphamidon (PHO, an organophosphorus insecticide) induced hepatotoxicity. GE was prepared from dried ginger and characterized for compound profile and antioxidant activity. Eight groups of albino rats (n = 6) were treated with 1/5th lethal dose of PHO for 5-20 days. Out of the treated 8 groups, 4 were simultaneously fed with GE (1 mg/kg body wt.) along with PHO. Alterations in the levels of hepatocellular oxidative stress (OS) markers in the treated groups indicated an enhanced generation of reactive oxygen species (ROS) and oxidative stress (OS). Upregulation of apoptotic markers, DNA fragmentation and appearance of apoptotic nuclei suggested induction of apoptosis in the liver cell that was found to be attenuated after GE treatment. Moreover, no toxicity and mortality was observed up to 100 mg/kg dose of GE for 30 days in the rat model studied. Thus, GE can be considered as an effective, economical and safe extract to circumvent PHO-induced hepatotoxicity. PMID- 26548078 TI - Characterization of coal fly ash nanoparticles and their induced in vitro cellular toxicity and oxidative DNA damage in different cell lines. AB - Coal combustion generates considerable amount of ultrafine particles and exposure to such particulate matter is a major health concern in the developing countries. In this study, we collected nano sized coal fly ash (CFA) and characterized them by scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), particle size analyzer (PSA) and transmission electron microscope (TEM), and investigated its toxicity in vitro using different cell lines. The imaging techniques showed that the coal fly ash nanoparticles (CFA-NPs) are predominately spherical shaped. The analyses have revealed that the CFA-NPs are 7-50 nm in diameter and contain several heavy metals associated with CFA particles. The studies showed significant amount of toxicity in all cell lines on treatment with CFA-NPs. The cytotoxicity and oxidative DNA damage caused by CFA-NPs were determined by inhibition of cellular metabolism (MTT), total intracellular glutathione (GSH), reactive oxygen species (ROS) and DNA fragmentation in cultured cell lines (Chang liver, HS294T and LL29). The cellular metabolism was inhibited in a dose-dependent manner in CFA-NPs treated cell lines. The CFA-NPs induced ROS and decreased the total intracellular glutathione with increased dose. Further, the CFA-NPs treated cells showed severe DNA laddering as a result of DNA fragmentation. PMID- 26548079 TI - Biological activity of Dolichos biflorus L. trypsin inhibitor against lepidopteran insect pests. AB - Protease inhibitors confer resistance in plants against insect pests by inhibiting larval gut proteases. Cultivars of Dolichos biflorus were screened for their inhibitory activity against midgut proteases of Pieris brassicae larvae. Seed extracts of developing and germinating seeds of HPK4 cultivar inhibited larval gut proteases of Spodoptera littoralis efficiently. Neonate larvae of P. brassicae fed on cabbage leaf discs coated with 0.025-2.50 mg protein (seed extract) resulted in 10-80% larval mortality and significantly reduced leaf area eaten and faecal matter as compared to control. The treated larvae had 40% less soluble proteins per mg faecal matter and there was similar decline in midgut proteases of treated larvae (@ 2.5 mg protein) compared to untreated ones after 5 days. The LC50 and LT50 value was calculated to be 1.05 mg/leaf disc and 4.8 days (2.5 mg protein), respectively for neonate larvae of P. brassicae. Significant reduction in egg hatching (75%) was observed in egg mass treated with 5.3 mg of crude inhibitor protein of mature seeds. This could be due to the inhibition of proteases involved in the hydrolysis of egg chorion proteins. The studies demonstrated the insecticidal activity of D. biflorus seed extracts. PMID- 26548080 TI - A microdroplet cell culture based high frequency somatic embryogenesis system for pigeonpea, Cajanus cajan (L.) Millsp. AB - A protocol for high frequency production of somatic embryos was worked out in pigeonpea, Cajanus cajan (L.) Millsp. The protocol involved sequential employment of embryogenic callus cultures, low density cell suspension cultures and a novel microdroplet cell culture system. The microdroplet cell cultures involved culture of a single cell in 10 MUI of Murashige and Skoog's medium supplemented with phytohormones, growth factors and phospholipid precursors. By employing the microdroplet cell cultures, single cells in isolation were grown into cell clones which developed somatic embryos. Further, 2,4-dichlorophenoxyacetic acid, kinetin, polyethylene glycol, putrescine, spermine, spermidine, choline chloride, ethanolamine and LiCl were supplemented to the low density cell suspension cultures and microdroplet cell cultures to screen for their cell division and somatic embryogenesis activity. Incubation of callus or the inoculum employed for low density cell suspension cultures and microdroplet cell cultures with polyethylene glycol was found critical for induction of somatic embryogenesis. Somatic embryogenesis at a frequency of 1.19, 3.16 and 6.51 per 10(6) cells was achieved in the callus, low density cell suspension cultures and microdroplet cell cultures, respectively. Advantages of employing microdroplet cell cultures for high frequency production of somatic embryos and its application in genetic transformation protocols are discussed. PMID- 26548081 TI - Interaction of mouse intestinal P-glycoprotein with oral antidiabetic drugs and its inhibitors. AB - Type 2 diabetes (T2DM) is a progressive insulin secretory defect accompanied by resistance to insulin, and thereby making glycemic control a major concern in the treatment of these patients. Oral drug administration, though a popular option for its non-invasiveness, suffer from poor bioavailability. It could be related to the efflux transport of intestinal P-glycoprotein (Pgp). In the present study, we explored the binding interactions of antidiabetic drugs i.e., sulfonylurea drugs (glimepiride, glipizide, glyburide) and rapid acting insulin secretagogues viz., nateglinide, repaglinide and rosiglitazone; and Pgp inhibitors i.e., Generation I (verapamil and tamoxifen), III (tetradrine and tariquidar), and natural inhibitors (fumagillin and piperine) in mouse Pgp model. Our results revealed that fumagillin piperine and verapamil possess maximum interaction energies with Pgp compared to antidiabetic drugs. These observations elucidate the role of fumagillin and piperine as potential natural compounds which could intervene in the efflux action of Pgp in extruding the antidiabetic drugs and may have implications for increasing efficacy of oral antidiabetic therapy. PMID- 26548082 TI - Q2N and E64G double mutation of ubiquitin confers a stress sensitive phenotype on Saccharomyces cerevisiae. AB - The eukaryotic protein, ubiquitin harbours a parallel beta-bulge in its structure which is formed by residues Glu64(1), Ser65(2) and Gln2(X). Despite their low % frequency of occurrence in parallel beta-bulges, the residues Gln2 and Glu64 have been totally conserved in ubiquitin. In a previous study, two single mutants UbQ2N and UbE64G were constructed by replacing the residues Gln2 and Glu64 with Asn and Gly, respectively to understand their importance. The choice of the residues for substitution was made on the basis of their high preference for existence in parallel beta-bulge, so that the structure of mutants remains unaltered and any functional differences observed would highlight the importance of Gln2 and Glu64 in ubiquitin biology. The results from this study established that yeast cells expressing either UbQ2N or UbE64G, displayed functional differences with respect to survival upon exposure to cycloheximide and degradation of substrates by ubiquitin fusion degradation (UFD) pathway. It describes construction of the double mutant UbQ2N-E64G and its characterization. Our results showed expression of UbQ2N-E64G in stress hypersensitive SUB60 cells led to significant decrease in growth rate and prolonged half-life of substrates of UFD pathway, besides failure of complementation under heat and antibiotic stresses, providing the reason for conservation of Gln2 and Glu64 in ubiquitin sequence. PMID- 26548083 TI - Pressing issues and family matters. PMID- 26548084 TI - The venerable Sheila Tlou. PMID- 26548085 TI - On being almost old. PMID- 26548086 TI - Canadians connect with, learn from global colleagues. PMID- 26548087 TI - Screening. PMID- 26548088 TI - Experts in their own right. PMID- 26548089 TI - Ethics in Practice: At End of Life--Part 1. PMID- 26548090 TI - The Ward Women of the Northwest Territories. PMID- 26548091 TI - Della Magnusson's one-stop shop. PMID- 26548092 TI - What's happening to patient engagement? PMID- 26548093 TI - Beautiful buttons. PMID- 26548094 TI - Will the health professions' messages emerge from the fog? PMID- 26548095 TI - [Clinical and MRI Findings in Patients with Congenital Anosmia]. AB - The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 +/- 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 +/- 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However, diagnosis of congenital anosmia is important, as its presence can lead to dangerous situations. Careful examination for hypogonadism is also required in people with anosmia. MRI examinations of the olfactory bulbs and sulci were useful for the diagnosis of congenital anosmia. PMID- 26548096 TI - [Investigation of Type I Thyroplasty Using Titanium Implant]. AB - OBJECTIVE: The aim of this study was to describe a new titanium thyroplasty medializing implant and evaluate its usefulness. MATERIAL AND METHOD: Retrospective study of 9 male patients with severe unilateral vocal fold paralysis after aortic-aneurysm surgery who underwent type I thyoplasty with arytenoid adduction under general anesthesia. Preoperative and postoperative glottal closure and voice function were evaluated by acoustic analysis (Jitter %, Shimmer %, NHR), stroboscopic findings, maximum phonation time, mean airflow rate, voice handicap index and computed tomography findings. These tests were evaluated before and 3 months after surgery. RESULT: All acoustic parameters improved after surgery. In stroboscopic findings, symmetrical mucosal waves were identified in 3 cases. Maximum phonation time prolonged, mean flow rate decreased and voice handicap index improved. In computed-tomography findings, breakage, deformation, dropped and migration of titanium plate were not identified. CONCLUSION: In surgery of vocal fold paralyzed patient, it is necessary to reconstruct vocal fold in physiological state at the time of phonation. Using the titanium plate developed for this purpose, all patients obtained good vocal improvement. PMID- 26548097 TI - [Combined Anterior Craniofacial Resection for Locally Advanced Ethmoid Carcinomas]. AB - OBJECTIVE: Carcinoma of the ethmoid sinus is very rare, and treatment for locally advanced tumors remains as a formidable challenge to the clinician. We reviewed cases of ethmoid carcinoma in which anterior craniofacial resection had been undertaken and evaluated the safety and validity of the operative methods. METHODS: We retrospectively reviewed 13 patients with ethmoid carcinoma who underwent combined anterior craniofacial resection. We evaluated the surgical procedures, complications, outcomes, local recurrence, and the survival rate. RESULTS: Coronal incision and anterior craniotomy were performed in all cases. Four out of 13 cases underwent ipsilateral orbital exenteration due to involvement of the orbital contents. There were no potentially fatal complications, except for two cases of epidural abscesses which were successfully cured. Positive surgical margins were observed in 6 patients, and they received postoperative radiotherapy and/or chemotherapy. Local recurrences occurred in 4 cases, and 3 died at 9, 11, and 49 months after the surgery. Distant metastasis was not observed during the observation period. The overall 5-year survival rate was 75.2% (Kaplan-Meier method). CONCLUSION: These tumors were safely removed without severe complications and postoperative mortality. Combined anterior craniofacial resection is an effective and safe option for treatment of locally advanced ethmoid carcinomas after various preoperative treatments. PMID- 26548098 TI - [A Case of Severe Hyponatremia Caused by Renal Salt Wasting Syndrome in Oropharyngeal Cancer]. AB - Hyponatremia is one of the electrolyte abnormalities frequently encountered in cancer therapy. Cisplatin is a well-known drug which can raise various adverse events, including hyponatremia. A male with advanced oropharyngeal cancer is presented in the present report, who was treated with radiotherapy with concurrent administration of cisplatin and who underwent a total of three episodes of severe hyponatremia in the course of therapy. The first two attacks of hyponatremia following cisplatin administration were accompanied by dehydration and excessive urination, and the patient recovered in one week with rehydration and salt supplementation. Excessive loss of salt in urine confirmed that these events were caused by renal salt wasting syndrome after cisplatin administration. On the other hand, the third attack was due to the syndrome of inappropriate antidiuretic hormone secretion after surgery for a bone fracture. Estimation of the extracellular fluid volume and salt intake/output balance is always believed to be necessary for the diagnosis and proper management of severe hyponatremia after chemotherapy-based treatment with cisplatin. PMID- 26548099 TI - [Survey on the Choice of the Treatment in Elderly Patients with Head and Neck Cancer]. AB - The elderly population has been increasing, in Japan. With this increase, the incidence of elderly patients with head and neck cancer is likely to increase concomitantly. Therefore, a strategy for addressing this problem must be defined. In this study, a questionnaire for head and neck cancer specialists, certified by the Japanese Society of Head and Neck Surgery, is analyzed. The survey was conducted in 225 head and neck cancer specialists, and 122 answers were complete and bare analyzed in this study. Comorbidity was found to be the most important factor in decision making for head and neck cancer, even though it is subclinical. Especially important was the cognitive state, the dysfunction of which might decrease the feeling of struggle against the disease. These results indicate that we must choose the appropriate treatment based on the evaluation of the physical and emotional condition of the patients and their families, not only on their age. However, this suggestion includes some problems, such as the fact that the criteria are not definite and the choice of the treatment might be at risk of being judged by only one doctor. PMID- 26548100 TI - [Complications Resulting from Taking Ear Impressions]. AB - In 2012, we carried out a study in a large sample to understand the secondary injuries caused during the taking ear impressions for hearing aids. This study is a follow-up of previous research conducted in 1986 (285 medical institutions) and 1999 (98 medical institutions). We posted a questionnaire survey to the otolaryngology departments of 3,257 medical institutions. The response rate to the questionnaire was 62.9% (2,050 of the 3,257 institutions), and the results indicated that 301 of the 2050 institutions (14.7%) had experience with secondary injuries, with a total of 460 cases reported. In 342 of the 460 cases (74.3%), the secondary injuries occurred at hearing-aid dealerships, followed by 67 cases (14.6%) at affiliated medical institutions, and 51 cases (11.1%) in other locations, including other medical institutions, rehabilitation counseling centers, and educational institutions. The most common type of secondary injury (298 cases, 64.8%) was caused by the presence of foreign bodies in the ear, which in turn was a result of complications occurring during the removal of residual ear impression material. Of these 298 cases, 32 required excision of the foreign bodies and surgical intervention under general anesthesia. The remaining 10 cases exhibited isolated tympanic membrane perforation without foreign body-related complications. Furthermore, 146 cases (31.7%) developed bleeding and otitis externa following removal of the ear impression, and there were reports of cases with bleeding that required long-term outpatient care and treatment. Therefore, since retention of a foreign body in the ear and tympanic membrane perforation can occur even in patients without a history of surgery or prior otologic history, adjustment of hearing aids requires prior otorhinolaryngological examination. Furthermore, because of the risk of secondary injury when taking ear impressions, this procedure must be performed with caution under the guidance of an otolaryngologist. PMID- 26548101 TI - [PSA and blood test diagnostics of prostate cancer]. AB - Gleason grading of tumor biopses is the only method to distinguish clinically significant prostate cancer. Local cancer is usually symptomless, and men would benefit from functional screening. The aim of improving blood test diagnostics is to find those for whom it is profitable on the basis of blood test to proceed to biopsies. Overdiagnosis would be simultaneously avoided. In blood test diagnostics, established use is made only of the levels of prostate-specific antigen (PSA) and free PSA. New methods for blood test diagnosis are "Prostate Health Index" and the four-kallikrein panel. PMID- 26548102 TI - [Hips have a hard time in ice hockey goalkeeper's butterfly technique]. AB - Hip problems have increased especially among young ice hockey goalkeepers and those using the butterfly technique. Femoroacetabular impingement (FAI) is a common cause of the symptoms. Although hip impingement may also be symptomless, it may later predispose to joint damages, especially in case of goalkeepers who are loading their hip. Diagnosis of the impingement is important in order to lessen any harmful effects. Magnetic resonance imaging is the most important investigation in addition to the elucidation of patient history and clinical condition. Conservative treatment includes changing the exercise, and making use of exercises supporting the hip. If secondary joint damages have already developed, surgical treatment is required. PMID- 26548103 TI - [Family-based psychosocial interventions for children with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder]. AB - Psychosocial family-based interventions--family therapy, cognitive-behavioral parent training and family-based treatment protocols--are empirically supported treatments for children with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. Well-researched interventions such as remote and group-based parent training programs relate to improvements in parenting quality, positive parenting, and the child's decreased ADHD and conduct behavioral problems, whereas individual family-based treatments are sometimes required, depending on symptom severity. Specific family-based treatment protocols are tailored for older children and adolescents with severe behavioral and emotional problems. Considering the above, empirically supported programs are used more in Finland, compared to licensed Anglo-American treatment protocols. PMID- 26548104 TI - [Magnetic resonance imaging of the brain in the monitoring of immune therapy of multiple sclerosis]. AB - Magnetic resonance imaging of the brain is currently the most sensitive method in detecting the lesions caused by multiple sclerosis. Assessment of the immunological treatment response used in the treatment of multiple sclerosis should be based on the clinical picture and brain MRI. T2-, flair- and T1-biased images, gadolinium enhancement and assessment of atrophy are required for MRI monitoring. In the first-line immune therapy MRI is taken at 6 to 12 months after starting the drug therapy, in fingolimod therapy after 6 to 12 months and 1 to 2 years, respectively, and in alemtuzumab and natalizumab therapy after one and two years. PMID- 26548105 TI - [Screening of congenital heart defects in the newborn--time to unify the practices of oxygen saturation screening in Finland]. AB - Saturation screening of congenital heart defects in the newborn takes place in Finnish maternity hospitals. Saturation screening has been shown to be a cost effective way to screen critical heart defects in the newborn. Screening aims to reveal the heart defect before potential circulatory collapse. Early diagnosis is important, as invasive therapeutic measures for congenital heart defects have been concentrated to one center. There are differences in the implementation of saturation screening. We therefore recommend unifying the screening system to conform with the recently published Nordic recommendation. Screening should be conducted during the first day of life by measuring the saturation values of both the right upper limb and one of the lower limbs. PMID- 26548106 TI - [What to do when my cancer patient is pregnant?]. AB - Cancers in pregnant women are rare and similar to those in women of similar, reproductive age. Diffuse large B-cell lymphoma differs in its course in pregnant women. Cancer treatment according to the guidelines is modified only according to what is necessary in the overall situation. The goal of the treatment is to secure the well-being of the mother and the fetus. Cancer surgery is successful on almost the same principles as in other patients. Drug therapies required by a severe cancer diagnosed in early pregnancy may jeopardize the health of both the mother and the fetus. Radiation therapy during pregnancy is generally not recommended. PMID- 26548107 TI - [Insulinomas in Tampere University Hospital Special Responsibility Area in 1980 2010]. AB - BACKGROUND: Insulin-producing neuroendocrine tumours (iNETs) are rare, but their incidence is increasing. We studied the incidence, clinical picture, diagnostics, and treatment of insulinomas diagnosed in 1980 to 2010. METHODS: Retrospective analysis of insulinomas diagnosed in Tampere University Hospital. RESULTS: We found 23 iNET cases corresponding to an incidence of 0.7/million/year. All had neuroglycopenic symptoms and 83% had autonomic ones. The median diagnostic delay (from first symptoms up to diagnosis) was 25 months. Preoperative imaging found the tumor in 87%. Twenty-one out of 22 patients who underwent surgery recovered completely. CONCLUSIONS: Despite improved imaging the diagnostic delay of iNETs remained unchanged. Hypoglycemia and insulinoma should be considered as a cause of unspecific, symptomatic attacks. PMID- 26548108 TI - [Peripheral ischemia and heart failure as complications of neoadjuvant therapy of bladder cancer]. AB - Cystoctemy is the standard therapy of bladder cancer that has spread to muscle. After five years from the surgery only 50% of the patients remain alive. Owing to poor prognosis, preoperative cytostatic chemotherapy for the patients has been commenced. Severe complications associated with the therapy are rare, and the results are promising in selected patients. We describe a patient case, in which necrosis of terminal segments of fingers and heart failure developed during preoperative chemotherapy. PMID- 26548110 TI - Harnessing natural resources for the benefit of mankind. PMID- 26548111 TI - Potassium channels and prostacyclin contribute to vasorelaxant activities of Tridax procumbens crude aqueous leaf extract in rat superior mesenteric arteries. AB - BACKGROUND: Previous studies have shown that aqueous extract of the leaf of Tridax procuinbens is capable of lowering blood pressure through its vasodilatory effects. In the present study attempt was made to examine the biological active components of T procuinbens leaf using GC-MS methods. We further investigated the role of K+ channels in the vasorelaxation effects of Tridax procumbens using rat isolated mesenteric artery. METHODS: The superior mesenteric artery isolated from healthy, young adult Wistar rats (250-300 g) were precontracted with phenylephrine (PE) (10(-7) M) and potassium chloride (KCl) (60 mM) and were treated with Various concentrations of aqueous extract ofT procumbens (0.9.0 mg/ml). The changes in arterial tension were recorded using a force-displacement transducer (Model 7004; Ugo Basil Varese, Italy) coupled to data capsule acquisition system. RESULTS: The results of GG-MS revealed the presence of linoleic acid. The T. procumbens extract (TPE) ranging from 0.5-9.0 mg/mI significantly (p<0.05) reduced the, contraction induced by (PE) and (KCl) in a concentration-dependent manner. The extract also antagonised the calcium-induced vasoconstriction (1(-9) - 10(-5)) in calcium-free with high concentration of potassium as well as. in calcium- and potassium free physiological solutions. The vasorelaxing effect caused by TPE was significantly (p<0.05) attenuated with preincubation of potassium channels blockers (Barium chloride and apamin), NO synthaseinhibitor (L-NAME), prostacyclin inhibitor (indomethacin), atropine; propranolol, and methylene blue while it was not affected by preincubation with glibenclamide and tetra ethyl ammonium, 4-aminopyridine (4-AP) and oxadiazolo quinoxalin (ODQ). CONCLUSION: The results of this study demonstrate that T procumbens extract causes vasodilatory effects by blocking calcium channels and the vasodilatory effect of the extract may also be due to stimulation of prostacyclin production and opening of small-conductance Ga2+ activated potassium channels. The observed effect of this extract may be probably due to the presence of linoleic acid in this extract. PMID- 26548112 TI - In vitro antimicrobial activity of crude ethanol extracts and fractions of Terminalia catappa and Vitex doniana. AB - BACKGROUND: The spread of microorganisms resistant to some antimicrobial agents necessitates the need to search for novel and effective antimicrobial agents. In this study, the antimicrobial activity of Terminalid catappa Linn. (Combretaceae) and Vitex doniana Sweet. (Verbenaceae), two Nigerian medicinal plants used in folk medicines for the management of various ailments related to microbial infections were evaluated. OBJECTIVES: To evaluate the antimicrobial activity of the crude ethanol extracts and fractions of the leaves and stem bark of T. catappa and V. doniana. METHODOLOGY: Four crude ethanol extracts and 16 (n hexane, ethylacetate, n-butanol and aqueous) fractions of leaves and stem bark of T. catappa and V doniana were evaluated for in vitro antimicrobial activity against fifteen (15) strains of bacteria and fungi. The antimicrobial activity was determined in a 96-well plate using a resazurin based broth microdilution method. Two standard antimicrobial drugs ampicillin and nystatin were included as positive control. RESULTS: The butanoL fraction of stem bark of T. catappa and ethanol crude extract of leaf of V don iana displayed the highest antibacterial activity with similar minimum inhibitory concentration (MIC) value of 93.75 microg/mL against S. aureus and B. subtilis. Furthermore, the ethyl acetate fraction of stem bark of T. catappa showed the highest antifungal activity with MIC of 187.5 microg/mL against A. sydowi. Amp icillin had MIC of 15.6 and 31.3 microg/mL against S. aureus and B. subtili, respectively while nystatin produced MIC of 3.9 microg/mL against A. sydowi. CONCLUSION: Termninalia catappa and Vitex doniana may serve as useful sources of plant derived antimicrobial agents. PMID- 26548113 TI - Comparison of postoperative pain in diathermy and conventional scalpel Skin incision after mastectomy in Ibadan, Nigeria. AB - INTRODUCTION: Pain control is a challenge after surgery. Inadequate control of acute postoperative pain in mastectomy patients may lead to chronic post mastectomy pain syndrome. The study aimed to compare the effect of diathermy incision with scalpel incision on the severity of acute postoperative pain after mastectomy. METHOD: Sixty three females had mastectomy under general anaesthesia. Thirty two patients had skin incisions made with scalpel while 31 patients with diathermy. Both groups received intraoperative Fentanyl and Tramadol. Tramadol was also employed as postoperative analgesic while Paracetamol was given as the rescue analgesic. The outcome measures were pain scores using visual analogue score (VAS) and analgesic consumption within the twenty four hours postoperatively. RESULTS: The mean VAS in the diathermy group versus scalpel group at 6th, 12, 18th and 24th hour post operatively were 11.84 +/- 6.15 mm versus 16.18 +/- 8.5 mm (p=0.001), 11.10 +/- 4.26 mm versus 15.84 +/- 5.12 mm (p=0.001), 11.07 +/- 4.15 mm versus 17.32 +/- 6.01 mm (p=0.001), 10.6 +/- 8.08 mm versus 19.19 +/- 8.7 mm (p = 0.001) respectively. The mean dose of Tramadol was 264 +/- 84 mg in the diathermy group versus 278 +/- 64 mg in the scalpel group p=0.189, three patients required rescue analgesic (paracetamol) in the diathermy group mean dose 1.5.7 +/- 0.54 g versus 7 patients in the scalpel group, mean dose 1.67 +/- 0.58 g p=0.75. CONCLUSION: Diathermy can contribute to reduction in the acute postoperative pain in patients undergoing mastectomy. PMID- 26548114 TI - Lifetime and 7-day alcohol consumption in the elderly, prevalence and correlates: Reports from the Ibadan Study of Aging. AB - INTRODUCTION: There is a dearth of information on alcohol consumption in the elderly in Africa. The aim of the study was to determine the prevalence of lifetime and 7 day alcohol consumption in a community sample of elderly Nigerians and the association of 7 day excessive alcohol consumption to several common health conditions. METHODS: Face-to-face interviews were carried out among 2,149 elderly persons aged 65 years and older, selected through a multistage stratified sampling method of households in the Yoruba-speaking areas of Nigeria (22% of Nigerian population). Using a daily inventory of drinking, lifetime and 7-day alcohol consumption estimates were derived. Excessive alcohol consumption was defined as use of more than 1 unit/day at a sitting or more than 7 units/week. Major depressive disorder was assessed with the WHO Composite International Diagnostic Interview; chronic general medical conditions were assessed by self reports. RESULTS: Majority (54.8%) of the respondents were lifetime abstainers. Past-week alcohol use was reported by 12.0% of men and 3.6% of women. Drinking rates declined with increasing age in both sexes (p < 0.05). Past week excessive alcohol consumption was less likely among persons residing in rural areas, OR = 0.41 95% CI (0.17-0.99) but more likely to be associated with chronic backache or neck pain OR = 2.04, 95% Cl, (1.0-4.59 and cognitive impairment OR=4.2, 95% CI, (1.21-15.1). CONCLUSION: Excessive consumption is relatively common among elderly males. Alcohol consumption in the elderly is associated with chronic pain, cognitive impairment and living in urban areas. PMID- 26548115 TI - Knowledge, determinants and unmet needs for postpartum family planning use among women attending immunization clinic at Bowen University Teaching Hospital, Ogbomoso, Oyo State, Nigeria. AB - BACKGROUND: Most women in extended post partum period often have desire to use family planning. Disappointedly, majority of such women end up having unplanned or unwanted children. Little is currently known about factors responsible for such unmet family planning need among Nigerian women. OBJECTIVES: To assess the prevalence and determinants of unmet need for post partum family planning (PPFP) among women in Oyo State, south- west, Nigeria. METHODOLOGY: This cross-sectional analytic study was carried out using systematic sampling technique among 444 women attending immunization clinic in Ogbomoso, Nigeria. A pre-tested questionnaire was used for data collection and data analysis. was done using SPSS version 17. Chi-square test and binary logistic regression were used for analysis. RESULT: The mean age of the respondents was 36?9. Majority (65.7%) of the respondents demonstrated poor knowledge on PPFP. More than half (54.0%) of them had unmet need for limiting while 46.0% had unmet need for spacing. Fear of side effects was the commonest reason for lack of PPFP use (17.4%). Unmet need was significantly associated with marital status, educational status and level of awareness about PPFP. Level of awareness was the only significant predictor of unmet need among our study participants (OR; 2.973, 95% C.I; 0.119-0.459). CONCLUSION: Our study shows a high unmet need for PPFP among women in Ogbomoso, thus there is need for a more programmatic focus on women in their extended post partum periods. There is need for more awareness program on PPFP to increase contraceptive uptake in Nigeria. PMID- 26548116 TI - Compliance with infection control practices by Veterinarians in Nigeria. AB - BACKGROUND: There is a global increase in morbidity and mortality due to zoonotic diseases hence there is a need to identify possible sources of infections to human population. This study assessed veterinarians' compliance with standard infection control practices (ICPs) for prevention of zoonosis in Nigeria. METHODOLOGY: A cross sectional survey of 320 veterinarians participating in the National Annual Conference of the Nigerian Veterinary Me ic Association was done in November, 2011 Characteristics related to compliance with standard infection control practices were assessed. Chi-square and logistic regression tests were done at 0.05 significant levels. More veterinarians (51.1% and 61.2%) did not comply with appropriate ICPs while carrying out medical procedures of necropsy and assisting in parturition. Those with longer years of practice (OR=0.42,95% CI=0.23-0.75) and with long working hours (OR=0.52, 95% CI=0.28-0.97) were less likely to comply with ICPS. Private practice veterinarians' were less likely than public practitioners to comply (OR=0.67, 95% CI = 0.15-0.69). Also veterinarians who had workplace IC policy were more likely than those without to be compliant with ICPs (OR=3.71, 95% CI = 1.87-7.37). CONCLUSION: Future conferences can be used to advise veterinarians on the importance of implementing appropriate IC measures. Also infection prevention practices laws and policies should be enacted to encourage compliance by veterinarians. PMID- 26548117 TI - Household survey on Human Papilloma Virus vaccine awareness among women of reproductive age in Ibadan, Nigeria. AB - BACKGROUND: Cervical cancer is the commonest female genital tract malignancy associated with high mortality in sub-Saharan Africa due to poor prevention plan. Human Papilloma Virus (HPV) is a necessary cause of cervical cancer, and the infection is vaccine preventable. Since the introduction of HPV vaccine, robust community surveys on awareness of the vaccine that capture end-users perspective is scarce. The aim of this study is to determine HPV vaccine awareness among women of reproductive age group. METHODS: This was a household survey that used multi-stage random sampling conducted amongst 1002 women aged 18-49 years from August to September 2012 in Mokola area, Ibadan, south western Nigeria. A self administered pre-tested questionnaire was used for data collection. Descriptive, bivariate and multivariable analyses were performed, and statistical significance was set at 95% confidence level. RESULTS: The mean age was 29.8 +/- 8.2 years and 49.9% had female children. Only 4.6% had heard of HPV vaccine. A significantly higher odds of HPV vaccine awareness was found among highly skilled women, those initiating sexual intercourse at older ages; women with multiple sexual partners and those aware that cervical cancer is preventable. CONCLUSION: The awareness of HPV vaccine is low. Policies and programs that will improve awareness utilising culturally sensitive messages are imperative. PMID- 26548118 TI - Anti-inflammatory and analgesic properties of Struchium sparganophora Linn leaves in mice. AB - BACKGROUND: Struchium sparganophora is a medicinal herb useful in the treatment of pain, fever, arthritis, rheumatism, neurological and mental disorders in traditional system of medicine in Nigeria and some other African countries. This study was carried out to evaluate the anti-inflammatory and analgesic properties of Struchium sparganophora in mice. METHODS: The anti-inflammatory effect of Struchium sparganophora was evaluated using; carrageenan-induced paw oedema and histamine-induced paw oedema in mice. The analgesic properties of Struchium sparganophora were investigated utilizing; formalin, tail immersion and acetic acid-induced abdominal constriction tests in mice, respectively. RESULTS: Struchium sparganophora (100 - 400 mg/ kg; p.o) did not produce a dose dependent anti-oedematogenic activity against carrageenan and histamine induced paw oedema. Similarly, the leaf extract also exhibited analgesic effects that can be said to be active both centrally and peripherally in PMID- 26548119 TI - Cost implications of treatment of diabetes mellitus in a secondary healthcare facility in Ibadan. AB - BACKGROUND: Diabetes and its complications remain a major health challenge in Nigeria. AIM: To evaluate the economic cost of type 2 diabetes mellitus in a secondary healthcare facility in Ibadan, Nigeria. METHODS: The study was carried out in Oyo state general hospital Ibadan, Nigeria using two methods of data collection. A retrospective study design in which data were extracted from case files of diabetic patients using a pre-designed data form and secondly with an Open-ended, Affirmation, Reflective listening and Summaries (OARS) method. Data was analysed using frequencies mean and correlation statistical tools. RESULTS: Majority of the patients (73%) earned less than $125 per month. Hypertension was the most common (98.08%) co-morbid disorder with diabetes mellitus and the most common complication noted was neuropathy (48.10%). Metformin was the most widely prescribed oral hypoglycemic agent (90.40%). The annual cost of diabetes mellitus was $20,827.37. for the 52 patients while the average annual cost of diabetes per patient was $400.52 but higher in age group 60-69 years. There was a significant correlation (p < 0.05) between age (at onset of diabetes and at registration at the healthcare facility) and total cost of drugs used. CONCLUSION: The study demonstrated that type 2 diabetes mellitus and its complications imposed significant economic burden on the patients. There is need for the policy maker of health sector in the country to plan towards reducing the financial burden of diabetes on the society. PMID- 26548120 TI - Psychosocial impact of wheelchair usage on individuals with mobility disability in Ibadan, Nigeria. AB - BACKGROUND: Wheelchairs provide individuals with mobility impairments opportunity for independent living within their environment. However, using this device may have psychosocial impacts with consequent influence on the quality of life of the users. The psychosocial impact of wheelchair usage among individuals with mobility disability in a Nigerian community was investigated. METHODS: The study is a descriptive cross-sectional survey. People who have been independent users of wheelchair for a minimum of six months prior to the study were recruited from centres for people with disabilities in Ibadan, Nigeria into the study. A profile of their use of the device was documented and the psychosocial impact of wheelchair was assessed using the Psychosocial Impact ofAssistive Devices Scale. Data were analysed using descriptive and inferential statistics at p = 0.05. RESULTS: Sixty consenting individuals with mobility disability participated in this study. Their mean age was 38.7 +/- 14.1 years. Majority (90%) were manual wheelchair users and two-thirds (63.3%) had been using the wheelchair for < or = five years. Approximately a third of the participants use their wheelchairs occasionally. There was no significant difference (p=0.26) in the psychosocial impact of wheelchair usage between male and female users. CONCLUSION: The psychosocial impact of wheelchair was similar between male and female users. However, the impact was higher on the self-esteem of male than female users and lower on their competence than that of their female counterparts. This may be due to stigmatization or a culturally-related unwillingness of men in our environment to be dependent on others. PMID- 26548121 TI - Case reports of adult colo-colonic intussusception. AB - BACKGROUND: Adult colo-colonic intussusception is a rare abnormality and it may pose a diagnostic challenge. OBJECTIVE: To report two cases of adult colo-colonic intussusception with benign lesion as the lead points. METHODS: The Clinical records of the two patients containing the management details were retrieved and reviewed. RESULTS: The 1st case was a 60 year old man presenting with a year history of recurrent left abdominal pain a two week history of fullness left upper and lower abdomen. Examination showed an 8cm by 6 cm mass in the left hypochondrium continuing with another 16cm by 8 cm mass spanning the left lumbar and left iliac fossa. Abdominal ultrasound scan showed a huge mixed echogenic mass in the central abdomen spanning the left hypochondriac, left lumber and suprapubic regions. He had exploratory laparotomy which revealed cob-cobonic intussusception involving the ascending colon up to sigmoid colon. He had subtotal colectomy done. The lead point was a hamartomatous polyp The 2nd case was a 35 year old man with a two month history of recurrent abdominal pain and haematochezia, a month history change in bowel habit and five day history of abdominal distension. Examination showed distended abdomen with generalised tenderness. There was a firm mass in the left hypochondrium extending to the left iliac fossa. Abdominal ultrasound scan confirm intussusception: Exploratory laparotomy showed perforation of transverse colon at the neck of cob-colonic intussusception involving the distal third of the transverse colon to the rectum. He had extended left hernicolectomy and Devine colostomy done. He died 36 h6urs post operation. The lead point was an inflammatory polyp. CONCLUSION: Adult colo colonic intussusception is an uncommon disease which may not present in a typical feature of intussusception as occur in children thus posing diagnostic dilemma. High index of suspicion with radiological investigation will serve to aid rapid and accurate diagnosis. PMID- 26548122 TI - The impact of political institution and structure on health policy making and implementation: Nigeria as a case study. AB - BACKGROUND: Typical of the political structure of the United States of America, Nigeria operates a federal presidential system of government. Political power is shared between the three levels of Federal, State and the Local Governments. The political affairs of the country at these levels are determined by elected politicians from different political parties, with different political and developmental ideologies. This scenario has implications on policy making and implementation especially in the health sector. This paper sought to discuss the type of political structures and institutions and, the effect of these on health policy implementation in selected countries, with emphasis on Nigeria. CURRENT STATUS OF FINANCING HEALTH CARE: The National Health Insurance Scheme (NHIS) was launched almost a decade ago but currently covers an estimated four percent of the population, majority of which are in the formal sector. The poor coverage of the scheme in Nigeria has been attributed to the type of political institution and structure it operates. This is evident with examples of some countries in the world; whereas, the scheme in Nigeria was implemented almost at the same time like in neighbouring Ghana, the scheme in Ghana has made a considerable progress. Likewise, prepayment scheme for health in Britain has been in practice for decades, the U.S.A. is just currently making progress in the implementation of a nationwide prepayment scheme despite several years of efforts. It is important to note that Nigeria and the U.S.A. has similar political institution and structure different from what Ghana and Britain have in common. CONCLUSION: The current low level of coverage of the NHIS in Nigeria is largely due to the type of adopted political institution and structure. The implications of this on the health status of the people and national development cannot be overemphasized. PMID- 26548123 TI - Looking to a capable future workforce. PMID- 26548124 TI - New Regulations' impact discussed. PMID- 26548125 TI - Europe's first children's hospital in a park. AB - Just a year after the centenary of the completion of the 1914-built children's hospital which it will soon replace, this autumn will see the opening of a new Alder Hey Children's Hospital in Liverpool, dubbed Alder Hey in the Park thanks to its attractive parkland setting. The 270-bedded hospital, designed by architects, landscape architects, and interior designers, BDP, and built by Laing O'Rourke, is located in Springfield Park on Liverpool's northern fringes, and features a highly striking external design, with the three distinctive 'fingers' housing the wards bordered by extensive greenery, and the buildings topped by green undulating roofs. All the inpatient bedrooms, and indeed many other internal spaces, will enjoy parkland views. The new hospital will also reportedly offer some of Europe's most advanced children's healthcare. HEJ editor, Jonathan Baillie, reports on the construction of this stunning new healthcare facility, where children's views were key in shaping the design. PMID- 26548126 TI - Ensuring cleaning's effectiveness. PMID- 26548127 TI - How can acute space be better used? PMID- 26548128 TI - More features, greater connectivity. AB - Changes in our political infrastructure, the continuing frailties of our economy, and a stark growth in population, have greatly impacted upon the perceived stability of the NHS. Healthcare teams have had to adapt to these changes, and so too have the technologies upon which they rely to deliver first-class patient care. Here Sarah Hunt, marketing co-ordinator at Aid Call, assesses how the changing healthcare environment has affected one of its fundamental technologies the nurse call system, argues the case for wireless such systems in terms of what the company claims is greater adaptability to changing needs, and considers the ever-wider range of features and functions available from today's nurse call equipment, particularly via connectivity with both mobile devices, and ancillaries ranging from enuresis sensors to staff attack alert 'badges'. PMID- 26548129 TI - Air quality for the 'clean side' examined. PMID- 26548130 TI - Thorough training and knowledge are key. PMID- 26548131 TI - Clean air's many benefits described. PMID- 26548133 TI - Danesbury upgrade brings plenty of colour. PMID- 26548132 TI - Robust, reliable systems paramount. PMID- 26548134 TI - Complex challenges on larger sites. PMID- 26548135 TI - Driving innovation through efficiency. PMID- 26548136 TI - Are Medicare bundles in your future? AB - To ensure they are well-positioned for an expansion by the Centers for Medicare & Medicaid Services of bundled payment, hospitals that are not participants in the Bundled Payments for Care Improvement initiative should take the following steps: Understand which organizations in their markets are already participating and which might participate. Understand care utilization patterns within their care delivery networks and how those patterns affect cost per episode. Identify high quality, cost-efficient postacute care providers and begin collaborating with them to further improve outcomes. Educate discharging physicians about the impact that choices related to postacute settings have on both beneficiary out-of-pocket obligations and overall cost of care. PMID- 26548137 TI - service line analytics in the new era. AB - To succeed under the value-based business model, hospitals and health systems require effective service line analytics that combine inpatient and outpatient data and that incorporate quality metrics for evaluating clinical operations. When developing a framework for collection, analysis, and dissemination of service line data, healthcare organizations should focus on five key aspects of effective service line analytics: Updated service line definitions. Ability to analyze and trend service line net patient revenues by payment source. Access to accurate service line cost information across multiple dimensions with drill through capabilities. Ability to redesign key reports based on changing requirements. Clear assignment of accountability. PMID- 26548138 TI - Finding the 'sweet spot' in value-based contracts. AB - Health systems pursing value-based contracts should address six important considerations: The definition of value. Contracting goals. Cost of implementation. Risk exposure. Contract structure and design. Essential contractual protections. PMID- 26548139 TI - Assessing the value in transactions involving multi-provider networks. AB - When seeking to determine the financial value of a multi-provider network, hospital finance executives should address the following considerations: Revenue projections. Shared savings revenue risk. Distribution of profits. Cost structure. Working capital requirements. PMID- 26548140 TI - How to avoid 'death by benchmarking'. AB - Hospitals and health systems should adopt four key principles and practices when applying benchmarks to determine physician compensation: Acknowledge that a lower percentile may be appropriate. Use the median as the all-in benchmark. Use peer benchmarks when available. Use alternative benchmarks. PMID- 26548141 TI - Connecting the dots: using 'big data' to build an efficient, integrated service line. AB - As seen in the case of musculoskeletal care, the broad steps hospitals and health systems should take to optimize service lines include: Understanding their market's demand for services. Guiding patients through integrated, patient centric care. Taking patient engagement to the next level. PMID- 26548142 TI - Market-driven health care and the Affordable Care Act. PMID- 26548143 TI - On the safe side. PMID- 26548144 TI - New MSSP ACO rule practicing the art of the possible. PMID- 26548145 TI - Solving the monetization conundrum. PMID- 26548146 TI - [Obstructive Sleep Apnea: review and a case presentation]. AB - Obstructive sleep apnea may be a life threatening situation if does not get proper attention. Risk factors are easy to find, therefore general dental surgeons should be aware of them and refer if needed. This literature review clearly explains how obstructive sleep apnea is diagnosed and treated. We present a case of a patient with severe obstructive sleep apnea (apnea hypopnea index of 87.5/hour), who underwent bi jaw surgery with 2 piece Le Fort 1 maxiilary advancement, mandibular bilateral sagittal split osteotomy (BSSO) advancement, and genial tubercle advancement. Post-surgery sleep study demonstrated near resolution of previously severe obstructive sleep apnea with overall apnea hypopnea index (AHI) of 3.7/hour consistent with a successful surgical outcome. PMID- 26548147 TI - [Perceived attractiveness and other characteristics of different male facial types before and after orthognathic surgery]. AB - Orthognathic intervention has not only profound implications on the individual's function and esthetics, but also on the perception of his surrounding environment. In this study, frontal and profile photographs of 3 groups of men (a control group with normal profile and prognathic and retrognathic profiles, before and after orthognathic surgery) were shown in random order to a group of 83 women, who were asked to rate the pictures according to attractiveness and several personality traits on an analog scale. Results show that men with normal profiles got the most positive scores on all categories. Men with prognathic profiles were perceived as more aggressive and assertive, while men with retrognathic profiles were perceived as less intelligent and reliable. After orthognathic intervention both retrognathic and prognathic groups had a significant improvement in their scores, which were closer to the normal profile group. PMID- 26548148 TI - [One stage combined endoscopic and per-oral buccal fat pad approach for large oro antral-fistula closure with secondary chronic maxillary sinusitis]. AB - There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean +/- SD age of 53.5 +/- 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9%), foreign body in sinus (n = 10, 22.2%) nasal congestion (n = 7, 15.5%), halitosis (n = 6, 13.3%) and pain (n = 5, 12.2%). Surgical complications included local pain (n = 2, 4.4%), persistent rhinitis (n = 2, 4.4%) and synechia (n = 1, 2.2%). One patient required revision surgery due, to an unresolved OAF. The OAF of all the other 44 patients (97.8%) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 +/- 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis. PMID- 26548149 TI - [Distraction osteogenesis of deficient alveolar bone prior to dental rehabilitation]. AB - Implant supported rehabilitation has become very common in treatment plans nowadays, yet many patients lack the vertical and horizontal bone dimensions required for endosseous implant insertion. Distraction osteogenesis is a technique in which bone is generated by progressive elongation of two bone fragments following an osteotomy or corticotomy. Distraction osteogenesis of the alveolar ridge as a treatment modality in implant dentistry is a very useful technique that allows for adequate bone formation suitable for implant insertion. Alveolar distraction can be unidirectional, bidirectional, multidirectional or horizontal. Alveolar distraction osteogenesis can be performed by using intraosseous distraction devices, intraosseous distraction implants or by extraosseous devices which are the most prevalent today. Distraction osteogenesis has many advantages such as gradual lengthening of the bone with no need for an autogenous bone graft and lack of the associated donor site morbidity as well as distraction of the surrounding soft tissue together with the transported bone. One of the major challenges when using alveolar distraction osteogenesis is controlling the vector of distraction, this problem should be further addressed in future researches. We describe different methods for alveolar distraction osteogenesis, including the surgical procedure, latency period, lengthening and consolidation period. We also discuss the advantages, disadvantages and complications of the method. In this manuscript a case of mandibular alveolar deficiency following mandibular fracture and loss of teeth and the alveolar bone is presented. This patient was treated by alveolar distraction osteogenesis with excellent results. This patient was later rehabilitated . using endosseous implants as demonstrated by radiographs. Alveolar distraction osteogenesis provides a method to regain both hard tissue and soft tissue without additional grafting and is an efficient modality in cases of medium to severe bone loss. PMID- 26548150 TI - [Minimal invasive implantology]. AB - Endoscopic surgery has changed the philosophy and practice of modern surgery in all aspects of medicine. It gave rise to minimally invasive surgery procedures based on the ability to visualize and to operate via small channels. In maxillofacial surgery, our ability to see clearly the surgical field opened an entirely new world of exploration, as conditions that were once almost impossible to control and whose outcome was uncertain can be now predictably managed. in this article we will descripe the advantage of using the oral endoscope during the dental implantology procedure, and we will describe a unique implant which enable us in combination with the oral endoscope to create a maxillary sinus lift with out the need of the major surgery with all of its risks and complication. PMID- 26548151 TI - [Facial femalization in transgenders]. AB - Transsexualism is a gender identity disorder in which there is a strong desire to live and be accepted as a member of the opposite sex. In male-to-female transsexuals with strong masculine facial features, facial feminization surgery is performed as part of the gender reassignment. A strong association between femininity and attractiveness has been attributed to the upper third of the face and the interplay of the glabellar prominence of the forehead. Studies have shown that a certain lower jaw shape is characteristic of males with special attention to the strong square mandibular angle and chin and also suggest that the attractive female jaw is smaller with a more round shape mandibular angles and a pointy chin. Other studies have shown that feminization of the forehead through cranioplasty have the most significant impact in determining the gender of a patient. Facial feminization surgeries are procedures aimed to change the features of the male face to that of a female face. These include contouring of the forehead, brow lift, mandible angle reduction, genioplasty, rhinoplasty and a variety of soft tissue adjustments. In our maxillofacial surgery department at the Sheba Medical Center we perform forehead reshaping combining with brow lift and at the same surgery, mandibular and chin reshaping to match the remodeled upper third of the face. The forehead reshaping is done by cranioplasty with additional reduction of the glabella area by burring of the frontal bone. After reducing the frontal bossing around the superior orbital rims we manage the soft tissue to achieve the brow lift. The mandibular reshaping, is performed by intraoral approach and include contouring of the angles by osteotomy for a more round shape (rather than the manly square shape angles), as well as reshaping of the bone in the chin area in order to make it more pointy, by removing the lateral parts of the chin and in some cases performing also genioplasty reduction by AP osteotomy. PMID- 26548152 TI - [Oral cavity cancer: epidemiology and early diagnosis]. AB - Cancer of the oral cavity (Oral cancer) is the 11th most common malignancy in the world, despite the general global trend of a slight decrease in the incidence of oral cancer, tongue cancer incidence is increasing. About 90% of tumors are subtyped to oral Squamous cell carcinoma (OSCC). The incidence and mortality of this tumor shows variability according to the geographic location in which it is diagnosed, however in the last decade an increase was seen in the percentage of young patients, especially patients with tongue cancer. The overall prognosis of this cancer is roughly 55-65%, this is probably due to late diagnosis. Early diagnosis of oral cancer is the most important factor affecting the overall survival and prognosis, thus several diagnosis methods have been developed in the past few years. Still, the prognosis did not improve as expected. Oral cancer biomarkers in saliva is as easy body fluid, for noninvasive detection. Several researches identified several possible biomarkers, but none was specific. In our review, the incidence and mortality of oral tumors pose a main health problem in many aspects all around the world, as well as differences in behavior of these tumors. We witnessed more cases of anterior tongue cancers affecting mainly the young age patient group, a two decades younger than the normal risk group of oral cancer. Several countries in Europe showed a significant increase of oral cancer prevalence, such as Germany, especially in men. Similar behavior was also reported in the United States, which showed a change in the risk groups. Studies have reported an alarming lack of awareness about oral cancer, its symptoms and early diagnosis. These gaps in knowledge need to be addressed by further public education, possibly targeted at high-risk groups. With the knowledge of possible, specific, early biomarkers, primary detection could improve the prognosis tremendously. Research on the salivary biomarkers of the disease would help to develop screening programs tailored more to the risk groups. PMID- 26548154 TI - Professionalism in Nursing. PMID- 26548153 TI - Maxillofacial surgery in the technological era. PMID- 26548155 TI - Member Profile. Beasts' Best Friend. PMID- 26548156 TI - Still changing: Medicare turns 50. PMID- 26548157 TI - 5 ways to assess readiness for value-based payment. PMID- 26548158 TI - Healthcare M&A: critical issues in today's fast-paced market. AB - In an accelerating market for healthcare mergers and acquisitions, parties to a potential deal should consider the following factors when assessing risk and reward: Economic, business, and cultural forces. Funding issues and financing structures. Potential complications during due diligence. The critical importance of effective postmerger integration. The numerous regulatory, tax, and accounting issues that can affect an acquisition. PMID- 26548159 TI - The call conundrum. AB - Physician pay for being on call to provide emergency department coverage has long been a headache for health systems, but a few careful steps can help mitigate future challenges: Proactively develop strategies and adhere to them consistently. Promote integrated specialty groups/departments. Pursue payer contracts that include key quality and total cost-of-care incentives. PMID- 26548160 TI - Looking afield: debt collection tips hospitals can borrow from banks. AB - When developing strategies for collecting on patient debt, hospitals can benefit from following the example of the banking industry: Banks take a "do-it-yourself" approach, working delinquent accounts in-house for as long as practical. They embrace technology to give in-house debt collectors optimal opportunity to connect with customers to work out terms for resolving debt. They strategically leverage outside collections agencies based on the makeup of their debt portfolio. PMID- 26548161 TI - Improving denials management at the enterprise level. AB - Providers have just one last chance to prepare for implementation of ICD-0. These three components are key to a successful transition: Strong leadership, proactive processes and technology, diligence with denials. PMID- 26548162 TI - Redefining patient responsibility for a new era. AB - In 2014, Ochsner Health System implemented a systemwide initiative to improve financial stability, resulting in a 36 percent increase in preservice and point of-service collections over the same period the previous year. Highlights of the program include: Executive support for the effort, as well as strong, systemwide support from a cross-functional group of influential stakeholders. Exceptions for medically urgent services to ensure the new approach is aligned with Ochsner's mission and values. Measurement and distribution of key metrics (e.g., deferral rate) by the program's leadership to drive performance improvement, dispel rumors, and ensure broad support from physicians. PMID- 26548163 TI - The coding countdown. AB - As the time for ICD-10 implementation draws near, hospitals and health systems should prepare not only for the switch but also for long-term compliance. Key areas of preparation include: Training of personnel, including coders and physicians. Ensuring IT systems are compliant. Monitoring third parties for compliance. PMID- 26548164 TI - Optimizing the back office. AB - The shift to value-based service calls for new attention to be paid to an area often ignored in such a system: the back office. To reduce administrative costs and maximize compensation, healthcare providers should: Stay current with rules and timelines. Monitor provider eligibility and performance. Prepare for performance data submission. PMID- 26548165 TI - The self-pay problem. AB - Development of a self-pay plan is key to improving collections. The five opportunities for providers to do this include: Pre-registration/scheduling. Admissions, time of service, discharge, post-billing. PMID- 26548166 TI - Laying the cable: making investments that will enhance organizational value. PMID- 26548167 TI - Timing: tax-exempt bond refunds. PMID- 26548168 TI - Hospital admissions increasingly are originating in urgent care. PMID- 26548169 TI - GrittingYour Teeth at Work? PMID- 26548170 TI - What Is Caring with Dignity? PMID- 26548171 TI - Not a Silly Question After All? PMID- 26548172 TI - Incivility in the Classroom (i.e., How to Trap a Teacher). PMID- 26548173 TI - See Me, See My Child: Glimpses into Autism Spectrum Disorder. AB - Autism Spectrum Disorder (ASD) is on the rise, with one in 68 children diagnosed with ASD. Families of children with ASD speak of being othered-feeling like outsiders in social situations. Because of ASD prevalence, all nurses need to understand current research, causes, symptoms, diagnosis, treatment, and how to offer effective support. Nurses within the faith community, especially parish/faith community nurses, can play a significant role in creating a welcoming and supportive environment for children with ASD and their families. PMID- 26548174 TI - After The Trenches: Spiritual Care of Veterans. AB - Over a million veterans seek mental healthcare through the Veterans Health Administration (VHA) every year. Many voice challenges to their spiritual beliefs, especially after deployment. Research supports that integrating spiritual care into mental health interventions improves the ability of veterans to cope. Mental health practitioners-healthcare professionals specializing in mental health--are key to incorporating spirituality into the mental healthcare of veterans, as well as collaborating with VHA chaplains. PMID- 26548175 TI - From Doing to Bring: Incorporating Faith into Diabetes Self-Care Education. AB - Millions worldwide live with diabetes and are challenged to make lifestyle changes. Nurses help patients learn strategies necessary for successful diabetes management. However, patients frequently view long-term behavior change as unachievable. This article offers educational strategies based on liturgical anthropology that can be incorporated into any diabetic self-care education program, but particularly in faith communities. Lifestyle habits are tightly interwoven with cultural, social, and spiritual belief. Liturgical anthropology explores how cultural and spiritual customs mold us and influence our behavior choices. PMID- 26548176 TI - Can Spiritual Care be TAUGHT via Simulation? AB - Nurse educators are challenged to find meaningful methods to teach spirituality throughout the curriculum. Simulation is one teaching strategy that offers real life situations in a less threatening environment. This article offers a simulation of a client in spiritual distress and describes student responses using the Situation, Background, Assessment and Recommendation (SBAR) tool. Simulation can be used to help students develop critical thinking and clinical reasoning skills for spiritual care. PMID- 26548177 TI - MEETING Spiritual Needs: A STUDY USING THE SPIRITUAL CARE COMPETENCE SCALE. AB - Healthcare literature suggests that many nurses fail to address patients' spiritual needs and/or identify signs of spiritual distress. A study was conducted to explore whether nurses in a medical center possessed the knowledge to assess patients' spirituality and design and implement a plan of spiritual care. The Spiritual Care Competence Scale was used to assess competence in spiritual care assessment and implementation; professionalization and improving quality; personal support and patient counseling; referral; attitude toward patient spirituality; and communication of spiritual needs. PMID- 26548178 TI - PREPARING HEALTH PROFESSIONS VOLUNTEERS TO SERVE GLOBALLY. AB - Scant literature exists to describe the global health and collaboration competence of international healthcare professional volunteers. An educational program to prepare volunteers for short-term service in resource-poor settings was developed. Pre- and post- program competence and team collaboration levels were assessed in 18 healthcare professionals. A significant improvement (p < .05) occurred in global health competence after education. Formal educational preparation of international health volunteers can enhance their overall effectiveness when serving in resource-poor settings. Extensive resources for global health education are referenced. PMID- 26548179 TI - NURSING FOR THE KINGDOM OF GOD. AB - The importance of nursing as Christ would is vital for Christian nurses. At one Christian school of nursing, students are taught the concept of Kingdom Nursing: focused, dynamic, patient-centered care, inspired by the qualities of Christ and influenced by the presence of the Holy Spirit in the life of the nurse. PMID- 26548180 TI - When Is It Right to Pray with a Patient? PMID- 26548181 TI - Servant Educators Shape Future of Nursing. PMID- 26548182 TI - Divine Appointment. PMID- 26548183 TI - Hitch a Ride! PMID- 26548185 TI - Certificate of Need...a perspective to consider.... PMID- 26548184 TI - SADA Communique. PMID- 26548186 TI - Continuing Professional Development. PMID- 26548187 TI - Fracture strength of cusp-replacing fibre-strengthened composite restorations. PMID- 26548188 TI - Self-reported musculoskeletal pain among dentists in South Africa: A 12-month prevalence study. AB - INTRODUCTION: Musculoskeletal trouble (ache, pain, discomfort) originating in the neck, shoulder, and back is a common occupational hazard among dental professionals worldwide, The significance of this problem justified research into the prevalence of these symptoms among dentists in South Africa for which there is currently no information. AIMS: The aim of this study was to investigate the one-year prevalence of self-reported musculoskeletal trouble in the neck, shoulder, and lower back areas among dentists in South Africa. METHODS: A survey questionnaire was forwarded to all members of the South African Dental Association whose email addresses were recorded on the Association data base. The email survey was performed using the previously validated Nordic Musculoskeletal Questionnaires. RESULTS: This cross sectional study revealed a self-reported 12 month prevalence of musculoskeletal trouble (ache, pain, discomfort) among dentists in South Africa of 77.9% involving the neck, 69.8% the lower back, and 72.4% the shoulders, Multiple regression analysis showed that a PMID- 26548189 TI - Dental management of children with special healthcare needs. AB - INTRODUCTION: Dental caries is a common condition amongst young children that negatively impacts on their quality of life, It is an added burden on children with special healthcare needs (CSHCN) who have an increased risk of developing caries due to the high sugar contents in their medications, regular consumption of cariogenic foods and a poor salivary flow. AIMS AND OBJECTIVES: to analyse the management of dental caries in CSHCN at a tertiary public hospital in South Africa. METHODS: A retrospective analysis was conducted of the dental and medical records of 374 medically compromised children presenting with dental caries. Dental treatment and anaesthetic techniques used were reviewed. RESULTS: Results indicated that the majority of CSHCN presenting with caries were managed by extractions (96.5%) under either local anaesthesia (73.3%) or general anaesthesia (26.7%). There was a lack of restorative care provided to these compromised children, CONCLUSIONS: Treatment by extractions may relieve discomfort and pain; however, early loss of teeth leads to functional, psychological, aesthetic and orthodontic problems, which can result in a further decline in the quality of life of these already compromised patients, Restorative treatment and prevention strategies are critical in managing caries in CSHCN in order to improve their quality of life, PMID- 26548190 TI - Scale. PMID- 26548191 TI - Oral medicine case book 60: Xeroderma pigmentosum. PMID- 26548192 TI - Over-servicing. PMID- 26548193 TI - Maxillo-facial radiology case 121. PMID- 26548195 TI - Team Dentistry in July. PMID- 26548196 TI - Jules Kieser--1950 - 2014. BSc BDS PhD DSc FLS FDSRCS(Ed) FFSSoc. PMID- 26548197 TI - Coding guidelines for dentists. PMID- 26548198 TI - Heather Cunningham Graham. Passed away July 2014. PMID- 26548199 TI - A review of child abuse and the role of the dental team in South Africa. PMID- 26548200 TI - The adoption of social media and social media marketing by dentists in South Africa. AB - OBJECTIVES: The purpose of the study was to identify and understand social media usage behaviour of dentists in South Africa, in general and in particular as part of their marketing strategy and to consider the potential determinants associated with these behaviours. METHODS: Dentists who are members of the South African Dental Association were requested to anonymously complete an online questionnaire. Apart from demographic information, respondents were asked to report on their use of social media and their adoption of social media marketing. One-on-one interviews were also conducted with three dentists, to gain a deeper understanding of their adoption of this marketing option. RESULTS: South African dentists have started to embrace social media and 50.2% interact through these channels at least once a day. The most popular social media platforms are GooglePlus and Facebook. Respondents use social media mainly for personal purposes, including staying connected to family and friends.. Only 13.2% of those responding currently use social media as a marketing tool, but the majority (83.5%) predict that such usage will increase in future. CONCLUSION: Social media marketing is a growing trend and will become more significant in future. Although respondents used social media regularly for personal purposes, most are only now starting to use it as a marketing tool. PMID- 26548201 TI - The influence of glide path preparation on the failure rate of WaveOne reciprocating instruments. AB - INTRODUCTION: The aim of this study was to determine the influence of two different glide path preparation methods on the fracture rate of the Primary 25/08 WaveOne reciprocating instrument. Preparation times for different glide path methods and total time for root canal preparation, with and without prior glide path preparation, were also calculated. MATERIALS AND METHODS: ISO 15, 0.02 taper Endo-Training-Blocks (n = 300) were selected and randomly divided into three main groups (n = 100): Group 1: no glide path (control); Group 2: glide path preparation with stainless-steel hand files; and Group 3: glide path preparation with rotary PathFiles. The time taken to prepare each glide path was recorded. The specimens in each main group were then randomly assigned into five subgroups (n=20). New Primary 25/08 WaveOne files were used for canal preparation in each subgroup. The outcome was measured by recording how many simulated canals could be shaped with one WaveOne reciprocating file in each subgroup before instrument breakage occurred. The average time it took to prepare each of the simulated canals was calculated and recorded. The data were collected and statistically analysed using the ANOVA / Bonferroni test. RESULTS: Glide path preparation with PathFiles was significantly faster than with hand files (P<0.001). After the glide path preparation had been performed with PathFiles, a greater number of simulated canals could be prepared before failure of the WaveOne file (P<0.001). Root canal preparation time was significantly shorter (P<0.001) when an initial glide path had been prepared with PathFiles. PMID- 26548202 TI - Race/ethnicity in biomedical research and clinical practice. AB - There is ongoing debate as to whether persons of different racial/ethnic groups are biologically significantly different, and, if such differences exist, whether they are relevant in relation to disease susceptibility and to treatment outcomes. There is also debate about the benefits of using race/ethnicity as a factor in clinical decision making, and as a variable in biomedical or public health research, because of the emotional sensitivities attached to race/ethnic categorisation. Such categorisation may also divert attention from underlying issues such as socioeconomic status and lack of access to modern health care. In this short article we will discuss these controversies, and will emphasize the importance of responsible and sensitive use of race/ethnicity as a variable in biomedical research and in clinical practice. PMID- 26548203 TI - Maxillo-facial radiology case 122. PMID- 26548204 TI - Oral medicine case book 61: Oral malignant melanoma. PMID- 26548205 TI - Minors' request for confidentiality. AB - Dentists must be cognisant of what the law requires and how they are expected to respond. When the law does not address an issue, the dentist would need to weigh the circumstances and consequences and do what he/she thinks is ethically appropriate and acceptable. The need to maintain confidentiality of any information given to us in our professional capacity is paramount. Patient autonomy and their absolute right to confidentiality must be ensured in almost all but the most exceptional circumstances. Patients have the ethical and legal right to expect a health professional to keep confidential the information provided during the course of their care. Disclosure of patient information is only permitted with the patient's consent or if there is an overwhelming public interest in disclosure as prescribed by the law. PMID- 26548207 TI - Consent to information. PMID- 26548208 TI - SADA Communique. PMID- 26548209 TI - Letter of appreciation. PMID- 26548210 TI - Dentistry in South Africa is gravely ill, sick to the core. PMID- 26548211 TI - Substance abuse: case management and dental treatment. PMID- 26548212 TI - A comparison of preload values in gold and titanium dental implant retaining screws. AB - This in vitro investigation compared the effect of using either gold or titanium retaining screws on preload in the dental implant- abutment complex. Inadequate preload can result in screw loosening, whilst fracture may occur if preload is excessive. These are the most commonly reported complications in implant-retained prostheses, and result in unscheduled, costly and time-consuming visits for the patient and the clinician. This study investigated changes in preload generation after repeated torque applications to gold and titanium screws. The test set-up consisted of an implant body, a cylindrical transmucosa abutment, and the test samples of gold and of titanium retaining screws. The implant bodies were anchored using a load cell, and the transmucosal abutments were attached using either gold or titanium retaining screws. A torque gauge was used to apply torque of 20Ncm, 32Ncm, and 40Ncm to the retaining screws. The preloads generated in each screw type were compared at each torque setting, and after repeated tightening episodes. In addition, the effect of applying torque beyond the manufacturers' recommendations was also examined. Gold retaining screws were found to achieve consistently higher preload values than titanium retaining screws. Preload values were not significantly different from the first to the tenth torque cycle. Titanium screws showed more consistent preload values, albeit lower than those of the gold screws. However due to possible galling of the internal thread of the implant body by titanium screws, gold screws remain the retaining screw of choice. Based on the findings of this study, gold retaining screws generate better preload than titanium. Torque beyond the manufacturers' recommendations resulted in a more stable implant complex. However, further investigations, with torque applications repeated until screw breakage, are needed to advise on ideal maintenance protocols. PMID- 26548213 TI - Oral medicine case book 62: CREST syndrome. PMID- 26548214 TI - Forensic dentistry case book 2: Dental identification of severely carbonised remains. PMID- 26548215 TI - Maxillo-facial radiology case 123. PMID- 26548216 TI - Ethical management of patients with hearing impairments. PMID- 26548218 TI - Research: Capricious or Controlled? PMID- 26548219 TI - SADA Communique. PMID- 26548220 TI - Demarcation between medical schemes and health insurance. PMID- 26548221 TI - Sugar leaves a bitter taste. PMID- 26548222 TI - Confronting some fallacies of SA's sugar consumption with scientific facts. PMID- 26548223 TI - Letter about dental decay, obesity shows that sugar industry is not to be trusted. PMID- 26548224 TI - Oral health needs and barriers to accessing care among the elderly in Johannesburg. AB - OBJECTIVES: The study sought to determine barriers to accessing oral health services amongst the elderly residing in retirement villages in Johannesburg. The objectives were to determine the normative and perceived oral health needs, the barriers experienced and the predictors of oral health utilisation. MATERIALS AND METHODS: This was a cross-sectional study. Three hundred and eight (n=308) participants were recruited from 10 retirement villages in Johannesburg. Data were collected from questionnaires and clinical oral examinations assessing the DMFT and CPITN scores. RESULTS: The clinical findings of the oral health status indicated a caries experience of 46%, whilst 58% of participants suffered from periodontal conditions. Sixty four percent (64%) acknowledged the need to visit a dentist, however only 28% of the study population had utilised oral health care in the past 12 months, due to perceived barriers. The barriers most frequently reported included the belief that they were not able to afford dental treatment and the lack of transport availability. The multivariate analysis indicated that a significant positive predictor of utilisation was Perceived Need. CONCLUSION: Though oral health access was freely available in the public sector and normative and perceived need for oral health care were high, the barriers experienced prevented 72% of the participants from utilising oral health services. PMID- 26548225 TI - Radix Entomolaris - a rare case series. AB - INTRODUCTION: The success of root canal treatment is determined by satisfying the basic principles of complete removal of the endodontic pathology through chemo mechanical cleansing of the root canals followed by shaping and then by obturation to provide the ideal hermetic seal. To achieve such success a thorough knowledge of the root canal anatomy is a basic requirement. Several anatomic variations of the mandibular molars have been reported among which is the reportedly rare Radix Entomolaris(RE), a mandibular molar with an additional root located lingually. AIMS AND OBJECTIVES: To present five cases of RE diagnosed pre operatively using radiographs and subsequently successfully endodontically treated. We also aim to highlight the considerations for the diagnosis and management of RE in general dental practice. CONCLUSION: Even though RE is rarely encountered in general dental practice, the possibility that it may occur warrants the need to have sufficient knowledge regarding diagnosis and the appropriate modifications in endodontic management of these teeth. Preparedness coupled with a carefully modified clinical approach aids in successful management of RE and ensures that these cases could be handled with ease. PMID- 26548226 TI - Halitosis as a product of hepatic disease. AB - OBJECTIVES: This study evaluated halitosis in patients suffering from hepatic disease. MATERIAL AND METHODS: Twenty-five patients (12 males and 13 females) aged between 16 and 73 years who had undergone treatment for liver disease were included in this study. Three halimeter recordings were performed to measure methyl mercarptan and hydrogen sulphite. Mean values were calculated and compared with normal values (75-120 ppb). The level of significance was set at P < .05. Results: Thirteen of the 25 subjects (52%) had normal Volatile Sulphur Compound (VSC) values (75-120 ppb). Twelve subjects (48%) recorded values ranging from 132 to 1112 ppb. There was no correlation between hepatic pathology and halitosis. Fifty-two percent of all subjects had poor oral hygiene, strongly correlated with high VSC values (P<0.05) whereas the remaining 48% with good hygiene had normal levels of VSC. CONCLUSIONS: Within the limitations of this study, high values of VSC were not associated with the presence of hepatic disease. PMID- 26548227 TI - Oral medicine case book 63: HIV-associated oral melanin hyperpigmentation. PMID- 26548228 TI - Maxillo-facial radiology case 124. PMID- 26548229 TI - Planning for treatment ethically. PMID- 26548231 TI - [Identification of Clinical Thymidine-Dependent Small-Colony Variants of Staphylococcus aureus by Using Matrix-Assisted Laser Desorption Ionization Time of-Flight Mass Spectrometry]. AB - In this study, the performance of MALDI-TOF MS was evaluated for the identification of clinical thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus. We performed identification of a total of 15 S. aureus TD SCVs by using biochemical tests, 16S rRNA gene sequencing and MALDI-TOF MS analysis. Although the biochemical method using MicroScan panels could not identify all isolates due to insufficient growth in the control well. MALDI Biotyper (Bruker Daltonics) could correctly identify all of them. Two sample preparation methods, the direct transfer-formic acid method and ethanol-formic acid method, for measurement by MALDI Biotyper made no difference in results. MALDI-TOF MS is useful identification of S. aureus TD-SCVs. PMID- 26548232 TI - [Study on the Sample Preservation Temperature and Period in Circulating MicroRNA Quantification Using Spike-In Control]. AB - MicroRNA in body fluid is called circulating microRNA and is expected to be a non invasive stable biomarker of various diseases. In real-time RT-PCR of circulating microRNA, synthetic non-human microRNA, such as cel-miR-39, is used as spike-in control RNA instead of endogenous control RNA. Spike-in control RNA, which is added into sera or plasma just before RNA extraction, does not reflect microRNA degradation in the period between blood sampling and RNA extraction. Therefore, it is essential to prevent degradation of circulating microRNA in this period for better reproducibility of the quantification of microRNA using spike-in control. To address this issue, we analyzed the stability of cel-miR-39 on ice and circulating miR-21 and miR-223 in whole blood and serum. The synthetic cel-miR-39 in RNase-free water was stable for at least 3 hours on ice. Degradation of miR-21 and miR-223 in whole blood was not observed for 3 hours at room temperature. However, miR-223 in serum was apparently degraded within 24 hours at 4 degrees C and the stability levels of miR-21 and miR-223 in serum were significantly different (fold changes of miR-21 and miR- 223 within 24 hours were 0.891 and 0.485, respectively). These results show that it is essential to avoid long-term storage of sera at 4 degrees C to prevent degradation of microRNA in the quantification of circulating microRNA using spike-in control. PMID- 26548233 TI - [Utility of a Simultaneous Detection Kit for Glutamate Dehydrogenase and Toxin A/B with Toxigenic Culture in the Diagnosis and Treatment of Clostridium difficile Infection]. AB - We examined how doctors evaluate the results of C. DIFF QUIK CHEK COMPLETE (COMPLETE) in the diagnosis and treatment of Clostridium difficile infection (CDI). A total of 887 stool samples submitted from 2012 to 2013 were examined with COMPLETE. Requested specimens among samples with discrepant results were inoculated onto CCMA plates and incubated under anaerobic conditions for 48 h, then retested by COMPLETE if positive culture results were obtained. Of the 887 specimens, 198 (22.3%) were glutamate dehydrogenase-positive and 73(8.3%) were toxin-positive. Of the 125 specimens yielding discrepant results, 106 specimens were cultured and retested, with 46 (43.4%, 46/106) proving toxin-positive. As a result, the total number of toxin-positive results increased from 73 (8.3%, 73/887) to 119 (13.4%, 119/887). This change was significant (p<0.01). We analyzed the relationship between doctor's decision-making and timing of receiving CD test results in 81 specimens among the discrepant results. Twenty four patients started treatment just after obtaining the first test result (29.6%, 24/81) and the toxin-positive ratio of the second test was 62.5% (15/24). The decision to start treatment was made after obtaining results of the second test in 48 patients, of whom 13 (16.0%, 13/81) started treatment, and the toxin positive ratio was 37.5% (18/48). The difference in toxin ratio was significant (p < 0.05). The increase in toxin-positive ratio in the final report facilitates diagnosis in patients with CDL Many doctors, however, started treatment before obtaining results from the second test, suggesting that the 3-day delay in report results represents a drawback for this system. PMID- 26548234 TI - [Point-of-Care Ultrasonography Developed in Emergency and Critical Care Medicine and Its Application to the Lungs]. AB - The performance of ultrasound (US) devices is improving every year, and more advanced US is being conducted in laboratory settings with high-end machines. Meanwhile, portable US devices, which have become less expensive and of a higher quality, have come into widespread use at bedsides in emergency rooms, intensive care units, and general wards. In recent years, the concept of point-of-care ultrasonography (POCUS) has been widely accepted. POCUS performed at the bedside in acute care settings has value if it gives clinicians useful clinical information in a short time. The findings are interpreted based on the vital signs, history, and physical examination during the scan, and the interpretations are rapidly applied for decision-making. In this article, we review the findings of lung US, which is one of the main fields in POCUS, as well as diagnoses and evaluations of pneumothorax and pulmonary edema in acute care settings. PMID- 26548235 TI - [Utility of Ultrasonography in Point of Care for Cardiovascular Disease]. AB - Echocardiography is a powerful noninvasive cardiovascular diagnostic tool. In the emergency room, an outpatient setting, and the intensive care unit, physician performed point-of-care (POC) echocardiography is particularly important to understand the concurrent pathophysiology of unstable patients. In POC echocardiography, the purpose of examination should be clearly decided in advance by performing careful symptom assessment and physical examination, including heart and lung auscultation. In this article, heart failure, cardiac murmur-, ischemic heart disease, and acute pulmonary artery thromboembolism are selected and overviewed to assess the utility of POC cardiovascular ultrasound. In heart failure, visual assessments of the left ventricular ejection fraction, chamber size ratio, and inferior vena cava diameter are important. An ultrasound lung comet is a very useful finding, suggesting the presence of lung congestion. In patients with a cardiac murmur, the source of the abnormal sound can easily be confirmed by the color Doppler signal in conjunction with chamber size assessment. On the other hand, judgment of the severity of valvular heart disease should be reserved for detailed echocardiography. In acute coronary syndrome, POC echo is extremely important for prompt diagnosis and complication assessment. An understanding of the coronary artery territory and method to detect regional wall motion abnormality in ischemic heart disease is necessary. Papillary muscle rupture and ventricular septal perforation are both fatal complications of myocardial infarction, and they should be kept in mind and pan-systolic murmur should be detected before echocardiography. In acute pulmonary thromboembolism, the right heart size and characteristic wall motion abnormality should be focused on using echocardiography in addition to tricuspid regurgitant flow velocity measurement. Femoral vein ultrasonography with a compression test should be performed for all patients with acute pulmonary thromboembolism to search for potential embolic sources. PMID- 26548236 TI - [Point-of-Care Abdominal Ultrasound]. AB - In this paper, abdominal ultrasound examination as a point-of-care examination (POCUS) is discussed. POCUS is very useful in various clinical situations, especially for the diagnosis of critically ill patients with non-specific symptoms. In patients with an unknown fever origin, POCUS can detect unexpected infection foci such as liver abscesses. Pseudomembranous colitis, which is one of the important causes of fever during/after the use of broad-spectrum antibiotics and sometimes difficult to diagnose or even suspect as the cause of fever, can also be diagnosed with POCUS. Malignancies such as malignant lymphoma are also frequent causes of fever of unknown origin and, with POCUS, we have diagnosed many cases with malignant tumors presenting only with low-grade fever. Abdominal fullness is another common symptom of critically ill patients. POCUS is very useful for differentiation among several diseases causing abdominal fullness. Ascites is expressed as anechoic fluid in the abdominal cavity, while bowel obstruction as bowel distention presenting the so-called keyboard sign. Urinary retention, often misdiagnosed as bowel obstruction or an abdominal tumor, is also easily diagnosed by POCUS. It is very difficult to detect the occult causes of exacerbation of the general condition and/or markedly abnormal laboratory data in critically ill patients under endotracheal intubation or the influence of sedative agents, which make it difficult for the patients to complain of their symptoms. Attending physicians should make the best of POCUS as a useful diagnostic modality for these patients. PMID- 26548237 TI - [Usefulness of POCUS in Orthopedic and Trauma Fields]. AB - Recently, musculoskeletal ultrasonography has been becoming more common for diagnosis and treatment by ultrasound-guided intervention in the field of orthopedics. Because musculoskeletal ultrasound technology has rapidly advanced in recent years, and has many advantages, including no exposure to radiation, non invasive, wide availability, cost-effectiveness, and the ability to be used in real-time in the general outpatient clinic. Traditional radiography was not able to detect soft tissue injury, but musculoskeletal ultrasonography enables the diagnosis of not only musculoskeletal disorders including soft tissue injury, but also fractures by dynamic examination. The first choice of diagnostic imaging should begin to shift to musculoskeletal ultra-sound from traditional radiography. PMID- 26548238 TI - [Application of Metabolomics for High-Resolution Phenotype Analysis]. AB - A metabolome, a total profile of metabolites, is placed downstream of a proteome. The metabolome is thought to be the result of the implementation of genomic information. In other words, the metabolome can be called a high-resolution phenotype. The easiest operation of metabolomics is integration to the upstream ome information, including the transcriptome and/or proteome. Such trials have been reported at a certain scientific level. In addition, metabolomics can be operated in stand-alone mode without any other ome information. Among methods of metabolomics, the author's group is focusing on metabolic fingerprinting, in which metabolome information is employed as an explanatory variant to evaluate the response variant. Metabolic fingerprinting techniques are expected to not only aid in analyzing slight differences depending on genotype differences, but also in clarifying dynamic variation among living organisms. The author introduces several good examples of studies which he performed. They are useful for understanding the power of metabolomics. In addition, the author discusses the latest technology for the analysis of metabolic dynamism. The author's group has developed a facile analytical method for semi-quantitative metabolic dynamism. The author introduces a novel method based on time-dependent variation in isotope distribution employing stable isotope dilution. PMID- 26548239 TI - [The Past and Future of Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus Infection]. AB - In Japan, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have decreased; however, human immunodeficiency virus (HIV) infection has increased. Antiviral treatment against these viruses has been established. With antiviral medicines, HBV DNA and HIV RNA levels decrease to under the detectable limits and HCV is completely eliminated from almost 90% of infected patients. Furthermore, the morbidities associated with hepatocellular carcinoma and acquired immunodeficiency syndrome (AIDS) have decreased. The: appearance of antiviral resistant HBV and HCV is a concern because long-term treatment is needed against these viruses. Patients infected with HBV in the past have the potential to develop de novo hepatitis with immunosuppressive treatment, in spite of being HBsAg-negative and with HBV DNA under the detectable level. PMID- 26548240 TI - [Advanced Testing and Laboratory for HBV, HCV, and HIV Infection]. AB - Most target substances for immunoassay of infectious disease are antigens or antibodies which do not exist in the human body. Therefore, the method to set reference values is different from chemistry or hematology testing. High sensitivity is required for infectious disease testing, particularly for screening. Also, its reference values (cut-off values) are set as low as possible. Therefore, a false-positive reaction can be caused due to slightly non specific reactions in infectious disease reagents. The specificities for infectious disease reagents were evaluated with 9 kinds of HCV antibody test kit and 9 kinds of HIV screening kit. The frequencies of false-positive results were 0.2-1.8 and 0.2-1.3%, respectively, and even a kit with a high specificity showed a false-positive result for 1 in 500 samples. The sensitivities for infectious disease reagents were evaluated with a newly developed super-high- sensitive HBs antigen assay kit and 8 kinds of chemiluminescence HBs antigen assay kit which are highly sensitive conventional kits. As a result, the super-high-sensitive kit was 10 to 40 times more sensitive than conventional kits. After introducing the super-high-sensitive kit to routine assays, 16 HBV-infected patients, who were not identified with the conventional kits, were detected for six months. On the other hand, we confirmed false-positive results due to contamination between specimens after introducing the super-high-sensitive kit. It is recommended to use the super-high-sensitive kit in a well-controlled environment to prevent contamination between specimens in order to generate highly reliable test results. PMID- 26548241 TI - [Hepatitis B Virus Infection: Current Trends and Issues]. AB - Hepatitis B virus (HBV) infection is a global public health problem. HBV has been classified into eight genotypes (A to H) based on complete nucleotide sequencing. The prevalence of specific genotype varies geographically. The rationale for treatment in patients with chronic hepatitis B is to reduce the risk of progressive chronic liver disease, such as cirrhosis and hepatocellular carcinoma. Treatment strategies for chronic HBV infection include interferon and nucleotide analogues (lamivudine, adefovir dipivoxil, entecavir, and tenofovir disoproxil). HBV persists in the body even after serological recovery from acute hepatitis B. Thus, individuals who have been exposed to HBV are at risk of the reactivation of infection, which may result in an increase in serum aminotransferases or a flare when the immune response is suppressed. Patients requiring immunosuppressive therapy should undergo serologic testing for markers of HBV infection. This topic review summarizes these issues related to the management of hepatitis B. PMID- 26548242 TI - [Progress in Examination and Treatment of Hepatitis C Virus]. AB - Hepatitis C virus (HCV) is one of the major pathogens causing liver cirrhosis and hepatocellular carcinoma. For a long time, standard therapy against HCV infection involved a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). However, the sustained virological response (SVR) rate with this therapy can be up to 50%. Therefore, to predict the interferon response prior to treatment, novel viral and host factors were explored, and several novel examinations were developed. Recently, several classes of novel direct-acting antivirals (DAAs) targeting protease, NS5A, and polymerase of HCV have been developed and tested in clinical trials. HCV protease inhibitors, simeprevir and telaprevir, have been approved for the treatment of genotype 1 HCV infection in Japan. Moreover, recently, IFN-free regimens, the NS5A inhibitor Daclatasvir, and protease inhibitor Asunaprevir combination therapy have been approved in Japan. Treatment outcomes have been improved; however, viral resistance against DAAs has become a new issue. The aim of this review was to summarize the progress in examination and treatment of hepatitis C virus. PMID- 26548245 TI - "Nurses need to vocalise their contributions". PMID- 26548243 TI - [Development of a Dual Detection Method with Fluorescence In Situ Hybridization and Immunostaining on Formalin-Fixed Paraffin-Embedded Tissue Sections--Molecular Pathological Detection Techniques and Their Applications to Pathological Diagnosis]. AB - Fluorescence in situ hybridization (FISH) has recently become important for pathological diagnosis. However, its practical applications is not widespread because FISH protocol with FFPE specimens is complicated. We report a dual detection method by overlapping FISH with fluorescent immunostaining on FFPE sections. This method is characterized by changing buffers for heat treatment without proteolytic enzyme treatment. Subsequent proteolytic enzyme treatment can be omitted using an antigen activation solution, pH9 (Nichirei Corporation), for heat treatment. After the pretreatment, dual detection was achieved by DNA FISH following RNA FISH and fluorescent immunostaining. This protocol visualized gene abnormalities and protein overexpression on the same sections. Of note, in poorly differentiated tumors containing both normal and tumor cells, the tumor cells were clearly identified on the sections, and FISH signals could be counted in these cells. In addition, HER2 mRNA overexpression and gene amplification were simultaneously detected in HER2-positive gastric cancer. Thus, this method should be widely applicable in clinical settings. PMID- 26548246 TI - Councils seek to save on nursing. PMID- 26548247 TI - Staff numbers at failing trusts are insufficient, report nurses. PMID- 26548248 TI - General practice nurse network is launched. PMID- 26548249 TI - Multi-bed wards pose higher risk of infection spread by staff. PMID- 26548250 TI - Nurse staffing levels in UK 'lag behind other wealthy nations'. PMID- 26548251 TI - Community matrons service slashes hospital admission rates. PMID- 26548252 TI - Patients value nurse cancer support line. PMID- 26548253 TI - Court finds NMC 'unduly lenient' towards 'misguided' nurse. PMID- 26548254 TI - Nurses rival doctors in AMD injections. PMID- 26548255 TI - "Patient experience is the secret to staying alive in the NHS". PMID- 26548256 TI - "Work together to support the vulnerable following discharge". PMID- 26548257 TI - Scheme helps tackle obesity in childhood. PMID- 26548258 TI - Reducing nurse medicine administration errors. AB - Errors in administering medicines are common and can compromise the safety of patients. This review discusses the causes of drug administration error in hospitals by student and registered nurses, and the practical measures educators and hospitals can take to improve nurses' knowledge and skills in medicines management, and reduce drug errors. PMID- 26548259 TI - How a patient perspective improved IV therapy. AB - Cystic fibrosis (CF) treatment is demanding and includes courses of intravenous antibiotics (IVAB), for which many patients are admitted to hospital. Our 35-bed adult respiratory ward delivers antibiotic doses up to four times a day but time pressures meant most patients did not receive their antibiotics on time. Many adults with CF are expert patients and plan their care with the healthcare team so a patient-nurse partnership was set up to resolve this issue. This article outlines a radical service change, based on a patient's comments, that was piloted and received positive feedback. PMID- 26548260 TI - Health visitors tackle childhood obesity. AB - One of Public Health England's priorities is to tackle obesity, particularly in children. Health visitors are ideally placed to identify and support families of children at risk from obesity, but research shows they lack the training and confidence to do so. This article describes a short-term local scheme that offered support by a specially trained health visitor to families in their own homes. The health visitor was trained using a family partnership model that teaches how to work with parents and carers to help them implement their own solutions. PMID- 26548261 TI - Assessing quality of life with incontinence. AB - This article reports on an evaluation of commonly recommended questionnaires to measure symptom severity and quality of life in women with urinary incontinence. Three questionnaires outperform the others and a robust assessment concludes that the International Consultation of Incontinence Questionnaire is the most practical tool for the busy practitioner. PMID- 26548262 TI - 60 seconds with Emma Munro. PMID- 26548263 TI - The value of a sea change. PMID- 26548264 TI - "Nurses need time to be compassionate". PMID- 26548265 TI - Nurse workforce growth stalls as NHS budgets bite. PMID- 26548267 TI - Epilepsy 'passport' aims to cut admission rates. PMID- 26548266 TI - Nurse education may be at risk in government spending review. PMID- 26548268 TI - Tributes paid to first Parkinson's specialist nurse. PMID- 26548269 TI - Nurses lack training for new psychosis treatment standards. PMID- 26548271 TI - MPs query compassion levels in provision of end-of-life care. PMID- 26548270 TI - CQC: Broadmoor trust has 'substantial' staffing issue. PMID- 26548272 TI - Child palliative care limited by nurse numbers. PMID- 26548273 TI - Training needed to avoid the past failings of Liverpool Care Pathway. PMID- 26548274 TI - Dehydration affects staff performance. PMID- 26548275 TI - Two-year study to assess benefit of productive ward programme. PMID- 26548276 TI - Grant win for liver service led by nurses. PMID- 26548277 TI - "There are many reasons why nurses avoid incident reporting". PMID- 26548278 TI - "Health promotion needs to be safe as well as better resourced". PMID- 26548279 TI - Pain that can be relieved should not be endured. PMID- 26548280 TI - The nurse's changing role in clinical research. AB - The possibility of systematically sharing clinical data more quickly and effectively has increased its potential to be used in research and, as a result of changes in policy over the last decade, all nurses can now be involved in clinical research. To do this, they must think actively about the quality of data they gather, as it becomes increasingly visible to more users and can be used many times for multiple purposes. This article outlines how the research environment has changed and the implications for clinical practice. PMID- 26548281 TI - How real-time data can improve patient care. AB - Ever since Florence Nightingale analysed the causes of death of British soldiers in the Crimea, interpreting and analysing data has been used to improve nursing. Now some forms of data, such as electronically recorded patient observations, are instantly available to nurses and managers. This article outlines how real-time data can be used to improve patient care, staff efficiency and overall management of hospitals. PMID- 26548282 TI - Ensuring cultural safety in nurse education. AB - Nursing courses now have a more culturally diverse mix of students and educators, and students need to consider how this influences learning and how their needs can be addressed. This article describes how the idea of "cultural safety" can promote professionally comprehensive and culturally coherent healthcare education in academic and clinical situations. PMID- 26548283 TI - Physiology--how the body detects pain stimuli. AB - Pain is the body's way of telling us something is wrong. It has a sensory and emotional component. This three-part series focuses on acute pain, describing the physiology of a normal and well-behaved pain pathway and how this relates to commonly used pain-management strategies. This first article introduces the pain system and how the body detects a threatening (noxious) stimulus. Part two describes how that pain message is transmitted to the spinal cord and the brain, and the response of the brain to the stimulus. The third article discusses the assessment of pain. PMID- 26548284 TI - 60 seconds with Lynsey Ayers. PMID- 26548285 TI - Igniting a passion for nursing. PMID- 26548286 TI - Don't pretend to be someone else. PMID- 26548287 TI - Surveillance for MRSA in a periodontal clinic. PMID- 26548288 TI - Laser assisted new attachment procedure (LANAP): strength of evidence. PMID- 26548289 TI - Demineralized dentin matrix and bone graft: a review of literature. PMID- 26548290 TI - [Clinical Implication of Insulin Resistance in Chronic Hepatitis C Patients]. AB - Chronic hepatitis C virus (HCV) infection is the leading cause for the development of liver cirrhosis and hepatocellular carcinoma, however, it also causes metabolic disorders. Insulin resistance is representative of these metabolic disorders, and not only leads to the development of diabetes but also affects the outcome of antiviral treatment with interferon. Historically, the standard of care for chronic HCV infection was pegylated interferon and ribavirin, but only 40-50% of HCV genotype 1 patients achieve a sustained virological response (SVR). We successfully established a pretreatment prediction model for the treatment outcome using a homeostasis model assessment of insulin resistance (HOMA-IR) and the interleukin 28B genotype (rs 8099917). In recent years, antiviral agents targeting viral proteins critical for HCV replication have become available. Of these, telaprevir, an HCV NS3/4A serine protease inhibitor, has been available in Japan since 2011. As a result, about 80% of patients with HCV genotype 1 can achieve SVR. Nonetheless, insulin resistance is associated with treatment failure, especially for difficult-to-treat patients. In the near future, almost all patients with chronic HCV infection will achieve virological clearance with combined direct antiviral agents, however, insulin resistance will remain a risk for hepatocellular carcinoma. Therefore, the prevention of obesity and avoidance of excessive alcohol intake are very important after achieving SVR. PMID- 26548291 TI - [Isolation of Neisseria elongata subsp. elongata Isolated from an Acute Myelogenous Leukemia Patient]. AB - Gram-negative cocci with a rod-like shape were isolated from a blood sample of a patient with acute myelogenous leukemia (AML). The 16S rRNA sequence of the isolate was similar to that of Neisseria elongata. Because previous reports about N. elongata as a pathogen have been extremely rare, more reliable identification seemed to be needed. We thus additionally performed a Multilocus Sequencing Analysis (MLSA) based on another four regions (argF, rho, recA, glnA), and confirmed the identification of N. elongata. The results from the MLSA identified the species; however, we could not identify the isolates into subspecies from the sequences. Three subspecies of N. elongata (N. elongata subsp. elongata, N. elongata subsp. glycolytica and N. elongata subsp. nitroreducens) were classified based on three definitive characteristics (catalase possession, nitrite reducibility, and acid from glucose). The results of the tests of three characteristics supported the identification of the isolate as N. elongata subsp. elongata. Therefore we determined the isolate from the AML patient to be N. elongata subsp. elongata. PMID- 26548292 TI - [Gene Mutations Associated with Macrolide-resistance and p1 Gene Typing of Mycoplasma pneumoniae Isolated in Yamagata, Japan, between 2004 and 2013]. AB - To clarify the epidemiologic features of Mycoplasma pneumoniae, we examined 358 M. pneumoniae strains isolated between 2004 and 2013 in Yamagata, Japan. Analysis of macrolide-resistance-associated 23S ribosomal RNA (rRNA) domain V mutations revealed 6 kinds of mutants (81 A2063G, 43 A2063T, 1 A2063C, 1 A2064C, 4 C2617G and 1 C2617 mutation). There were only two mutants before 2009, but mutants A2063T and A2063G increased in 2009 and from 2010, respectively. The annual ratio of mutants varied from 20.4% to 76.4% between 2009 and 2013. Typing of the p1 gene revealed 4 types; 278 type 1, and 3 kinds of type 2 variant strains (10 type 2a, 5 type 2b and 65 type 2c). Type 1 strains accounted for between 85.2% and 100% of isolates from 2004 to 2011, whereas type 2 variant strains increased by 26.5% and 66.1% in 2012 and 2013, respectively. These results indicate that type 1 strains may have been replaced by type 2 variant strains in 2013. Furthermore, the ratio of type 1 strains with a 23S rRNA mutation was 65.1% in 2012 and 95.2% in 2013, but none of the type 2 variant strains had this mutation. In conclusion, type 1 strains with macrolide-resistant mutations appeared in 2006 and increased from 2009. In contrast, type 2 variant strains, which increased in 2012 and became predominant in 2013, showed no mutations. PMID- 26548293 TI - [Evaluation of the Number of Varicella Patients Estimated by Prescription Surveillance]. AB - OBJECT: It is important to know the precise number of varicella patients infected for evaluation of routine immunization and anti-bioterrorism attack using smallpox. Prescription Surveillance (PS) has been providing the estimated number of varicella patients up to the present. However, the estimated number of varicella patients cannot be validated because to date there has been no other comparable precise method of estimation. Recently, all electronic medical claims nationwide (NDB) have been disclosed. In this paper, we compare the number of varicella patients estimated by PS with NDB data, and adjust the number estimated with PS, if necessary. METHOD: For both NDB and PS, we used the monthly data from April, 2010 to March, 2013. The estimation of the number of varicella patients from the PS data was adjusted by the proportion of estimated number based on PS to the one based on NDB in the entire study period. Moreover, we adjusted it month by month, if the former method may not be enough to compensate for the discrepancy between the two datasets. RESULTS: The average discrepancy between NDB and PS was 48.00% in three years. By the adjustment using NDB in the three years, the discrepancy was improved to 11.49%. However, seasonal patterns of overestimation or underestimation were found. Conversely, by the adjustment using NDB month by month, the discrepancy was greatly reduced to 4.33%. Moreover, the seasonal patterns of overestimation or underestimation disappeared. CONCLUSION: The number of patients based on NDB would appear the most precise number, however, there may be a delay of about one year before it becomes available. On the other hand, PS data are updated every day and provide us with the up-to-date situation. This paper found that combining the timeliness of the PS data and preciseness of the NDB data will provide substantial benefit for public health. PMID- 26548294 TI - [Nasopharyngeal Hib Carriage Among Healthy Children Attending Daycare Centers in Yokohama After One Year of a Publicly Funded Vaccine Program]. AB - Yokohama city started a regular, free vaccine program for Haemophilus influenzae type b (Hib) from February of 2011. This study was completed to verify the effectiveness of the vaccine on the nasopharyngeal Hib carriage among healthy children attending daycare centers in the Isogo area. The research was conducted during the late spring (Jun--Jul) and fall (Oct-Nov) of 2012. There was a significant decrease in the Hib carriage rate (spring 8.8%, fall 1.6%). During this period there was no increase in the Hib vaccine coverage. The Hib carriage rate of each daycare center was 0-18.4% in spring and 0-4.9% in fall. There was no significant relationship between the rate of non immunized children and that of Hib carriage. This improvement in nasopharyngeal Hib carriage shows the impact of community immunity. PMID- 26548295 TI - [Frequency and Characterization of EPEC and EAggEC Isolated in Kawasaki City]. AB - Thirty isolates of enteropathogenic Escherichia coli (EPEC) and 32 isolates of enteroaggregative E. coli (EAggEC) were isolated from 1,029 stool samples collected from Spring 2012 to December 2013 in Kawasaki city with the polymerase chain reaction (PCR) method targeting eae and aggR genes. Among the 30 EPEC and 32 EAggEC isolates, only 9 strains of EPEC and 8 strains of EAggEC were typed with the commercial O-antisera, whereas the majority of strains were untypable. However, several O-untypable EPEC and EAggEC strains were suggested to harbor the same O-antigen because of the detection of several examples of the same H antigen. Analysis of the HEp-2 cell adherence test showed positive for only 2 strains (6.6%) of 30 EPEC isolates, meanwhile it showed positive for 16 strains (50.0%) of 32 EAggEC isolates. From these data, we concluded that EAggEC might be more virulent than EPEC, although both EAggEC and EPEC were isolated with almost similar rates from collected stool specimens. PMID- 26548296 TI - [Serovars and Drug-Resistance of Salmonella Strains Isolated from Domestic Chicken Meat in Tokyo (1992-2012)]. AB - A total of 477 Salmonella strains isolated from retail domestic chicken meat during 1992-2012 in Tokyo, were examined regarding their serovars and drug resistance. These strains were detected in 469 (29.8%) of 1,576 samples. The detection rate in every two years was 10.1% to 46.3% of the range. Serological typing results showed that 477 strains were classified into 22 serovars excepting 2 untypable strains. Among them, S. Infantis (312 strains) was the most prevalent, followed by II O4: b: [e, n, x] (S. II Sofia) (71 strains), S. Hadar (20 strains), S. Typhimurium (20 strains), S. Manhattan (12 strains), S. Schwarzengrund (9 strains), S. Agona (7 strains), and other 15 serovars (24 strains). Results of the antibacterial drug susceptibility test for 477 strains revealed that 89.9% was resistant to some of the 12 drugs tested, and multidrug resistant strains accounted for 90.2% among them. The frequencies of resistance to each drug were 81.8%; 77.8%, 45.5%, 33.3%, 11.3%, 9.6%, 2.9%, 0.6%, 0.6% and 0.2%, in order with high frequency, for SM, TC, KM, ST, NA, ABPC, CP, FOM, CTX and CAZ, respectively. None of the strains was resistant to NFLX or IPM. Three CTX-resistant strains were CTX-M type extended-spectrum beta-lactamase (ESBL) producers, and the group of CTX-M type ESBL genes were CTX-M-2 group (2 strains) and CTX-M-9 group (1 strain). CAZ-resistant 1 strain was an ESBL producer, but the ESBL gene was not determined. PMID- 26548297 TI - [Necrotizing Soft Tissue Infection Caused by Serratia marcescens in a Patient Treated with Tocilizumab]. AB - We report herein on a case of community-acquired necrotizing soft tissue infection caused by Serratia marcescens. The patient had been treated with prednisolone, tocilizumab and tacrolimus for rheumatoid arthritis. Since Gram staining of the tissue revealed Gram negative rod bacteria, ceftriaxone and clindamycin were administered as empiric therapy. Tissue culture revealed S. marcescens. Ceftriaxone was continued according to the antibiotic sensitivity. She underwent debridement of necrotic tissue and continued ceftriaxone for 17 days. She recovered and was discharged after skin grafting. PMID- 26548298 TI - [Two Cases of Rapidly Progressive Community-acquired Pneumonia Due to Pseudomonas aeruginosa]. AB - Pseudomonas aeruginosa is a significant causative bacterium in hospital-acquired pneumonia and nursing and healthcare-associated pneumonia, but it seems to be rare in community-acquired pneumonia (CAP). We report two cases of severe CAP due to P. aeruginosa. Case 1: A 52-year-old man was referred to our hospital for chest and back pain. He was being treated for diabetes mellitus and had a long history of smoking. Chest images showed consolidation in the right upper lobe. Soon after hospitalization, he developed sepsis shock and died seven hours later. Case 2: A 73-year-old man with a history of heavy smoking was referred to our hospital for right chest pain. Chest images showed right upper lobe pneumonia. Although wide-spectrum antimicrobial agents were administrated, he died ten hours after admission. In both cases, there was a rapid progression to death, despite administration of a broad spectrum of antibiotics and treatment for sepsis. In cases of CAP involving the right upper lobe, the possibility of bacteremia and rapid progress should be considered. PMID- 26548299 TI - Yield of Computed Tomography at Baseline Staging of Melanoma. AB - BACKGROUND: Current guidelines call for baseline imaging only for very high-risk (T4b) primary cutaneous melanomas. OBJECTIVES: To estimate the frequency of computed tomography (CT) at baseline staging of primary cutaneous melanoma and the diagnostic yield of CT; and to describe the types and frequencies of incidentaloma findings. MATERIAL AND METHODS: Cross-sectional study of cutaneous melanoma cases (tumor classifications Tis to T4bN0M0) attended between 2008 and 2014 in a specialized melanoma unit. Reports of CT scans performed during baseline staging were reviewed to determine the frequency of positive scan results, incidentaloma findings, unit cost for detection of metastasis, and factors associated with the decision to order CT. RESULTS: CT results were available for 310 of the 419 patients included (73.99%). The tumor classifications were as follows: Tis, 17; T1, 137; T2, 71; T3, 48; and T4, 37. The CT results were negative in 81.61%, and incidentalomas were found in 18.06%. Additional primary tumors were found in 2 patients (0.64%), and metastasis was identified in one patient (0.32%). The cost of finding the case of metastasis was ?71,234.90. A T2 tumor classification (odds ratio [OR], 8.73) and age under 70 years (OR, 3.53) were associated with greater likelihood of CT being ordered. Excision of the primary tumor in the melanoma unit (OR, 0.08) was associated with less likelihood of ordering CT. CONCLUSIONS: The results for this patient series support current recommendations restricting CT at baseline to cases where there is high risk of metastasis (stagesiiC-iii). PMID- 26548301 TI - The end of gating? An introduction to automated analysis of high dimensional cytometry data. AB - Ever since its invention half a century ago, flow cytometry has been a major tool for single-cell analysis, fueling advances in our understanding of a variety of complex cellular systems, in particular the immune system. The last decade has witnessed significant technical improvements in available cytometry platforms, such that more than 20 parameters can be analyzed on a single-cell level by fluorescence-based flow cytometry. The advent of mass cytometry has pushed this limit up to, currently, 50 parameters. However, traditional analysis approaches for the resulting high-dimensional datasets, such as gating on bivariate dot plots, have proven to be inefficient. Although a variety of novel computational analysis approaches to interpret these datasets are already available, they have not yet made it into the mainstream and remain largely unknown to many immunologists. Therefore, this review aims at providing a practical overview of novel analysis techniques for high-dimensional cytometry data including SPADE, t SNE, Wanderlust, Citrus, and PhenoGraph, and how these applications can be used advantageously not only for the most complex datasets, but also for standard 14 parameter cytometry datasets. PMID- 26548300 TI - Effects of 2-methoxyestradiol on apoptosis and HIF-1alpha and HIF-2alpha expression in lung cancer cells under normoxia and hypoxia. AB - Hypoxic tumor cells are known to be more resistant to conventional chemotherapy and radiation than normoxic cells. However, the effects of 2-methoxyestradiol (2 ME), an anti-angiogenic, antiproliferative and pro-apoptotic drug, on hypoxic lung cancer cells are unknown. The aim of the present study was to compare the effects of 2-ME on cell growth, apoptosis, hypoxia-inducible factor 1alpha (HIF 1alpha) and HIF-2alpha gene and protein expression in A549 cells under normoxic and hypoxic conditions. To establish the optimal 2-ME concentration with which to carry out the apoptosis assay and to examine mRNA and protein expression of HIFs, cell growth analysis was carried out through N-hexa-methylpararosaniline staining assays in A549 cell cultures treated with one of five different 2-ME concentrations at different times under normoxic or hypoxic growth conditions. The 2-ME concentration of 10 mM at 72 h was selected to perform all further experiments. Apoptotic cells were analyzed by flow cytometry. Western blotting was used to determine HIF-1alpha and HIF-2alpha protein expression in total cell extracts. Cellular localization of HIF-1alpha and HIF-2alpha was assessed by immunocytochemistry. HIF-1alpha and HIF-2alpha gene expression was determined by real-time PCR. A significant increase in the percentage of apoptosis was observed when cells were treated with 2-ME under a normoxic but not under hypoxic conditions (p=0.006). HIF-1alpha and HIF-2alpha protein expression levels were significantly decreased in cells cultured under hypoxic conditions and treated with 2-ME (p<0.001). Furthermore, 2-ME decreased the HIF-1alpha and HIF-2alpha nuclear staining in cells cultured under hypoxia. The HIF-1alpha and HIF-2alpha mRNA levels were significantly lower when cells were exposed to 2-ME under normoxia and hypoxia. Our results suggest that 2-ME could have beneficial results when used with conventional chemotherapy in an attempt to lower the invasive and metastatic processes during cancer development due to its effects on the gene expression and protein synthesis of HIFs. PMID- 26548302 TI - Knowledge, attitudes and practices with regard to the presence, transmission, impact, and control of cystic echinococcosis in Sidi Kacem Province, Morocco. AB - BACKGROUND: This study is a component of a large research project on five major neglected zoonotic diseases (NZDs) including cystic echinococcosis and was undertaken in the Province of Sidi Kacem over a period of four years (April 2009 March 2013). METHODS: Questionnaires were administered at community level in a total of 27 communes and visits were made to all of the 10 abattoirs situated in the Province, to collect qualitative data on determinants of transmission for disease in humans and animals. More specifically, community knowledge, attitudes and practices related to cystic echinococcosis were assessed, as well as the extent to which local customs and behaviours may promote transmission. Abattoir infrastructure and practices, and their role in perpetuating disease transmission were also critically evaluated. RESULTS: The results show that only 50 % of people have heard of the disease, and of those, only 21 % are aware of the dog's role in disease transmission. Sixty-seven per cent of respondents stated that dogs are fed ruminant organs deemed unfit for human consumption. Owned dogs have access to the family home, including the kitchen, in 39 % of households. The extent of this close proximity between humans and animals is even more pertinent when one considers that dogs are omnipresent in the community, with an average of 1.8 dogs owned per household. The unrestricted access of dogs to abattoirs is a huge issue, which further promotes disease transmission. CONCLUSION: This study would suggest that the high prevalence of cystic echinococcosis in humans and animals in Morocco is largely due to three factors: 1) abundance of dogs 2) engagement in risky behaviour of the local population and 3) poor abattoir infrastructure and practices. This has serious implications in terms of the socio economic impact of the disease, especially for rural poor communities. PMID- 26548303 TI - Ferritic Alloys with Extreme Creep Resistance via Coherent Hierarchical Precipitates. AB - There have been numerous efforts to develop creep-resistant materials strengthened by incoherent particles at high temperatures and stresses in response to future energy needs for steam turbines in thermal-power plants. However, the microstructural instability of the incoherent-particle-strengthened ferritic steels limits their application to temperatures below 900 K. Here, we report a novel ferritic alloy with the excellent creep resistance enhanced by coherent hierarchical precipitates, using the integrated experimental (transmission-electron microscopy/scanning-transmission-electron microscopy, in situ neutron diffraction, and atom-probe tomography) and theoretical (crystal plasticity finite-element modeling) approaches. This alloy is strengthened by nano-scaled L21-Ni2TiAl (Heusler phase)-based precipitates, which themselves contain coherent nano-scaled B2 zones. These coherent hierarchical precipitates are uniformly distributed within the Fe matrix. Our hierarchical structure material exhibits the superior creep resistance at 973 K in terms of the minimal creep rate, which is four orders of magnitude lower than that of conventional ferritic steels. These results provide a new alloy-design strategy using the novel concept of hierarchical precipitates and the fundamental science for developing creep-resistant ferritic alloys. The present research will broaden the applications of ferritic alloys to higher temperatures. PMID- 26548304 TI - Early Vascular Aging: A New Target for Hypertension Treatment. AB - Vascular aging represents a progressive procedure involving biochemical, enzymatic, and cellular changes of the vascular tree. Early vascular aging (EVA), is defined as the inappropriate for age of vascular damage. Increased for age arterial stiffness is a biomarker that should be considered as a cardiovascular (CV) risk factor that can be manipulated. EVA is a new tool for guidance in everyday clinical praxis for patients at increased CV risk or a positive family history of early onset of cardiovascular events, such as stroke or coronary artery disease. Understanding the mechanisms promoting or protecting from EVA, a process that is in close relationship with CV diseases. The role of hypertension treatment against the development of vascular damage is important and different strategies could have a considerable impact on future vascular health. PMID- 26548305 TI - Cardiac Chamber Volumetric Assessment Using 3D Ultrasound - A Review. AB - When designing clinical trials for testing novel cardiovascular therapies, it is highly relevant to understand what a given technology can provide in terms of information on the physiologic status of the heart and vessels. Ultrasound imaging has traditionally been the modality of choice to study the cardiovascular system as it has an excellent temporal resolution; it operates in real-time; it is very widespread and - not unimportant - it is cheap. Although this modality is mostly known clinically as a two-dimensional technology, it has recently matured into a true three-dimensional imaging technique. In this review paper, an overview is given of the available ultrasound technology for cardiac chamber quantification in terms of volume and function and evidence is given why these parameters are of value when testing the effect of new cardiovascular therapies. PMID- 26548306 TI - Assessing Myocardial Metabolism with Hybrid PET Imaging: Instrumentation, Concepts, and Workflows. AB - Hybrid imaging devices including PET/CT and SPECT/CT have seen a great success since these scanners found their way into clinical routine - although this success is mainly based on the use in oncological imaging. But also the advent of PET/MRI holds great promise. The combined assessment of molecular imaging and morphology making use of the variety of PET tracers and the high spatial resolution from CT or MRI has the potential of an increased diagnostic accuracy all imaging but especially in cardiovascular questions. We put special emphasis on PET/MR although the experience is still limited. However, as the use of MR imaging in the assessment of myocardial viability as a prime example where assessing myocardial metabolism - even if done so indirectly - is so widespread in clinical reality, this appears to be justified. Thus, in this review, we aim to outline technical characteristics of hybrid imaging systems and highlight their use in cardiovascular diseases and their applications. PMID- 26548307 TI - Hyperpolarized (13)C MR Angiography. AB - Magnetic resonance angiography (MRA) is a non-invasive technology that can be used for diagnosis and monitoring of cardiovascular disease; the number one cause of mortality worldwide. Hyperpolarized imaging agents provide signal enhancement of more than 10, 000 times, which implies large reduction in acquisition time and improved spatial resolution. We review the role of hyperpolarized 13C agents for MR angiography and present the literature in the field. Furthermore, we present a study of the benefit of intra-arterial injection over intravenous injection of hyperpolarized agent for cerebral angiography in the rat, and compare the performance of two standard angiographic pulse sequences, the gradient echo (GRE) sequence and the balanced steady-state free precession (bSSFP). 2D coronal cerebral angiographies using intra-arterial injections were acquired with a GRE sequence with in-plane resolution of 0.27 mm and matrix size 256x128, and 2D coronal cerebral angiographies were acquired with a bSSFP sequence with in-plane resolution of 0.55 mm and matrix size 128x64. The bSSFP sequence provides higher SNR in phantoms than the GRE sequence. Similarly, intravenous injections are imaged with higher SNR with the bSSFP sequence, where the signal destruction of the GRE sequence is avoided. However, for intra-arterial injections, the bSSFP sequence results in strong artefacts, and the GRE sequence is preferred. Hyperpolarized MRA presents many challenges and cannot currently compete with conventional contrast enhanced MRA. Further research may change this since hyperpolarization is still an immature methodology. PMID- 26548308 TI - Technological Innovations in Magnetic Resonance for Early Detection of Cardiovascular Diseases. AB - Most recent technical innovations in cardiovascular MR imaging (CMRI) are presented in this review. They include hardware and software developments, and novelties in parametric mapping. All these recent improvements lead to high spatial and temporal resolution and quantitative information on the heart structure and function. They make it achievable ambitious goals in the field of magnetic resonance, such as the early detection of cardiovascular pathologies. In this review article, we present recent innovations in CMRI, emphasizing the progresses performed and the solutions proposed to some yet opened technical problems. PMID- 26548309 TI - Cross-Talk Between Adipose Tissue Health, Myocardial Metabolism and Vascular Function: The Adipose-Myocardial and Adipose-Vascular Axes. AB - Alterations in myocardial metabolism and blood flow have been described in patients with metabolic disorders, cardiovascular disease and cardiomyopathies, and have been implicated in the pathogenesis or prognosis of cardiac conditions. Adipose tissue dysfunction occurs in the above categories of patients. Adipose tissue plays a fundamental role in the modulation and selection of nutrients reaching the myocardium, and adipocytes secrete adipokines and other molecules affecting myocardial metabolism and regulating vascular function. In turn, the myocardium secretes a series of peptides affecting adipose tissue metabolism, and adipose tissue vascularization and perfusion contribute to the maintenance of adipose tissue health. This review addresses the reciprocal interaction linking adipose tissue to myocardial metabolism and vascular function. We summarize evidence of factors released by adipose tissue that affect cardiac metabolism and vice versa. Then, we address the role of adipose tissue in regulating vascular health, and examine whether adipose tissue hypoperfusion is causative or defensive of adipose tissue dysfunction. PMID- 26548310 TI - Air Pollution Exposure and Blood Pressure: An Updated Review of the Literature. AB - Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk factors for premature mortality worldwide, a potential relationship between these factors would have tremendous public health repercussions. Therefore, the aim of this review is to summarize recent evidence linking air pollution and BP. Epidemiological findings demonstrate that particulate pollutants cause significant increases in BP parameters in relation to both short and long-term exposures, with robust evidence for exposures to PM2.5. Moreover, recent epidemiological studies suggest a positive association between residence within regions with higher levels of ambient PM and an increased incidence and prevalence of overt hypertension. Studies provide consistent results that elevated concentrations of pollutants increase hospital admissions and/or emergency visits for hypertensive disorders and also support that PM levels increases BP in vulnerable subsets of individuals (pregnant women, high CV risk individuals). In this context, PM-mediated BP elevations may be an important pathway which acts as a potential triggering factor for acute CV events. Mechanistic evidence illustrates plausible pathways by which acute and chronic exposures to air pollutants might disrupt hemodynamic balance favoring vasoconstriction, including autonomic imbalance and augmented release of various pro-oxidative, inflammatory and/or hemodynamically-active mediators. Together these responses may underlie PM-induced BP elevations; however, full details regarding the responsible mechanisms require further studies. As a consequence of the ubiquity of air pollution, even a small effect on raising BP and/or the prevalence of hypertension, i.e. the major risk factor for mortality and morbidity worldwide, would have enormous global public health implications. PMID- 26548311 TI - All for Statins and Statins for All; An Update. AB - Statins exert beneficial effects on cardiovascular [CV] outcomes as well as on inflammation and oxidative stress. The widespread use of statins for both primary and secondary CV disease prevention is based on the evidence from large randomized controlled trials. The benefits of statin treatment outweigh any harm in high risk patients. In this narrative review, we provide an update on several aspects of statin treatment based on the most recent evidence in this field. PMID- 26548312 TI - Markers of Atherosclerotic Disease: What do they Mean? Current Opinion and Future Trends. AB - The response to the harm caused by risk factors related to atherosclerosis may consist of clinical-signs of cardiac and/or blood vessel ischemic pathology sometimes accompanied by arrhythmias and heart failure-, metabolic- signs of altered oxygen transport and pro-thrombotic changes of coagulation-fibrinolysis cascade-, and sympathetic features due to nerve stimulation, which cause changes in heart rate and blood pressure. Moreover, some special categories like women have the responses, which are influenced by their endocrine constellation. There is a different predisposition towards the markers of atherosclerosis in premenopausal woman, who displays atherogenic effects, and in women after the menopause who respond similarly to that of men. Finally, oxidative stress, which is a strong pro-thrombotic factor, increases the development of an atherosclerotic lesion. From these data, there is no doubt that a large number of factors, primarily smoking and endothelial dysfunction influence the cardiovascular system causing a major incidence of cardiovascular events. In addition, there would be evidence that some factors related to atherosclerosis should be considered as an etiologic (causal) factor of cardiovascular alterations because they can lead, in the long run, to an irreversible damage to the heart and blood vessels. PMID- 26548313 TI - Research Ethics in the Context of Transition: Gaps in Policies and Programs on the Protection of Research Participants in the Selected Countries of Central and Eastern Europe. AB - This paper examines the ability of countries in Central and Eastern Europe (CEE) to ensure appropriate protection of research participants in the field of increasingly globalizing biomedical research. By applying an analytical framework for identifying gaps in policies and programs for human subjects protection to four countries of CEE-Belarus, Latvia, Lithuania, and Poland, substantial gaps in the scope and content of relevant policies and major impediments to program performance have been revealed. In these countries, public policies on the protection of research participants lack consistency and reliable mechanisms for their implementation. Impediments to program performance most often relate to inadequacies in the national research ethics systems with regard to organizational structure, budgetary support, supervision, and training. The level of research ethics capacity varies from country to country and depends on socio economic and political factors of post-communist transition. The breadth and depth of the problems identified suggest that the current level of protection for research participants in CEE might be inadequate to the challenges posed by the globalization of biomedical research. In CEE countries, there is a need for strengthening research ethics capacity through modification of relevant policies and improvement of program management. The differences among the countries call for further research on identifying the best approaches for filling the gaps in the policies and programs aimed at ensuring effective protection of research participants. PMID- 26548315 TI - Sexual Functioning and Cognitions During Sexual Activity in Men With Genital Pain: A Comparative Study. AB - Male genital pain is frequently associated with sexual dysfunction, and some studies suggest it is influenced by cognitive factors. However, there is little evidence on how these factors discriminate male genital pain from other sexual problems. This study intends to explore differences on sexual functioning and self-reported cognitions during sexual activity between men with genital pain, men with sexual dysfunction, and sexually healthy men. A total of 134 men divided in three groups based on their clinical condition (i.e., genital pain, sexual dysfunction, or no sexual/pain complaints) and matched for demographic variables completed measures of sexual functioning (IIEF) and thoughts during sexual activity (SMQ). Findings showed that men with genital pain and men with sexual dysfunctions reported significantly lower levels of overall satisfaction with sexual life, compared to men without sexual problems. Additionally, men with genital pain and men with sexual dysfunctions presented significantly more failure anticipation thoughts in comparison to sexually healthy men. Overall, findings emphasize the role of negative cognitions as a common factor associated with male genital pain and sexual dysfunctions, suggesting that genital pain should be regarded as a sexual problem and that clinical interventions should include sex therapy techniques as well as cognitive-behavioral procedures. PMID- 26548316 TI - Investigational drugs targeting 5-HT6 receptors for the treatment of Alzheimer's disease. AB - INTRODUCTION: There are significant efforts invested into the discovery and development of novel treatments for Alzheimer's disease. While current discovery efforts and most scientific discussions seem to focus on disease-modifying therapy, there are several symptomatic therapy approaches that are being actively pursued. The goal of this review is to summarize the recent developments in the field of 5-HT6 receptor antagonists, a principle that has been extensively characterized preclinically and is now undergoing critical phases of clinical development. AREAS COVERED: The article covers the current status of 5-HT6 receptor antagonists in clinical development. It also discusses the underlying mechanisms for the observed procognitive effects. The article is based on a search for investigational drugs using the key words '5-HT6', 'cognition', 'dementia', 'Alzheimer's disease', 'Phase II' and 'Phase III' in various databases and from conference abstracts. EXPERT OPINION: After some period of little or no development activities, the field of 5-HT6 receptor antagonists attracted a lot of attention with three companies (GSK, Pfizer and Lundbeck) confirming aggressive development plans and initiating pivotal Phase II and III studies. These studies will be critical to prove that 5-HT6 receptor antagonists have a symptomatic efficacy profile that can be differentiated from that of currently used agents (cholinesterase inhibitors and the NMDA-antagonist memantine). Furthermore, there are several sets of data that point at a disease modifying potential of this class of agents and these effects are likely to receive critical exploration if the ongoing symptomatic trials bring 5-HT6 antagonists closer to clinical use. PMID- 26548314 TI - Shared genetic aetiology of puberty timing between sexes and with health-related outcomes. AB - Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 * 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 * 10( 12)). We find five novel loci for puberty timing (P<5 * 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease. PMID- 26548317 TI - Metabolic engineering of light-driven cytochrome P450 dependent pathways into Synechocystis sp. PCC 6803. AB - Solar energy provides the energy input for the biosynthesis of primary and secondary metabolites in plants and other photosynthetic organisms. Some secondary metabolites are high value compounds, and typically their biosynthesis requires the involvement of cytochromes P450s. In this proof of concept work, we demonstrate that the cyanobacterium Synechocystis sp. PCC 6803 is an eminent heterologous host for expression of metabolically engineered cytochrome P450 dependent pathways exemplified by the dhurrin pathway from Sorghum bicolor comprising two membrane bound cytochromes P450s (CYP79A1 and CYP71E1) and a soluble glycosyltransferase (UGT85B1). We show that it is possible to express multiple genes incorporated into a bacterial-like operon by using a self replicating expression vector in cyanobacteria. We demonstrate that eukaryotic P450s that typically reside in the endoplasmic reticulum membranes can be inserted in the prokaryotic membranes without affecting thylakoid membrane integrity. Photosystem I and ferredoxin replaces the native P450 oxidoreductase enzyme as an efficient electron donor for the P450s both in vitro and in vivo. The engineered strains produced up to 66mg/L of p-hydroxyphenylacetaldoxime and 5mg/L of dhurrin in lab-scale cultures after 3 days of cultivation and 3mg/L of dhurrin in V-shaped photobioreactors under greenhouse conditions after 9 days cultivation. All the metabolites were found to be excreted to the growth media facilitating product isolation. PMID- 26548318 TI - [Use of multiple regression models in observational studies (1970-2013) and requirements of the STROBE guidelines in Spanish scientific journals]. AB - BACKGROUND: In medicine and biomedical research, statistical techniques like logistic, linear, Cox and Poisson regression are widely known. The main objective is to describe the evolution of multivariate techniques used in observational studies indexed in PubMed (1970-2013), and to check the requirements of the STROBE guidelines in the author guidelines in Spanish journals indexed in PubMed. METHODS: A targeted PubMed search was performed to identify papers that used logistic linear Cox and Poisson models. Furthermore, a review was also made of the author guidelines of journals published in Spain and indexed in PubMed and Web of Science. RESULTS: Only 6.1% of the indexed manuscripts included a term related to multivariate analysis, increasing from 0.14% in 1980 to 12.3% in 2013. In 2013, 6.7, 2.5, 3.5, and 0.31% of the manuscripts contained terms related to logistic, linear, Cox and Poisson regression, respectively. On the other hand, 12.8% of journals author guidelines explicitly recommend to follow the STROBE guidelines, and 35.9% recommend the CONSORT guideline. CONCLUSIONS: A low percentage of Spanish scientific journals indexed in PubMed include the STROBE statement requirement in the author guidelines. Multivariate regression models in published observational studies such as logistic regression, linear, Cox and Poisson are increasingly used both at international level, as well as in journals published in Spanish. PMID- 26548319 TI - [Multifactorial program for the prevention of falls: A multifactorial proyect in the rural area]. PMID- 26548320 TI - Propofol Use in the Elderly Population: Prevalence of Overdose and Association With 30-Day Mortality. AB - PURPOSE: Geriatric patients are more sensitive to the anesthetic effects of propofol and its adverse effects, such as hypotension, than is the general population; thus, a reduced dose (1-1.5 mg/kg) is recommended for the induction of anesthesia. The extent to which clinicians follow established dosing guidelines has not been well described. Therefore, we investigated the prevalence of propofol overdose in the elderly population to determine whether propofol overdose occurs and is associated with increased hypotension and 30-day mortality. METHODS: In this retrospective study in patients who received propofol for the induction of general anesthesia, data on demographic characteristics, preoperative medications, intraoperative management, and 30-day mortality were collected. The dose of propofol used for the induction of anesthesia and the median blood pressure in the pre- and immediate postinduction periods were determined. Hypotension was defined as either: (1) a decrease in mean arterial pressure (MAP) of >40% concurrent with a MAP of <70 mm Hg; or (2) a MAP of <60 mm Hg. FINDINGS: A total of 17,540 patients were included in the analysis; 4033 (23.0%) were aged >65 years. The median (interquartile range) propofol dose in the group aged >65 years was 1.8 (1.4-2.2) mg/kg, above the recommended dose, in comparison to 2.2 (1.9-2.5) mg/kg in younger patients. On multivariate analysis, increased propofol dose was associated with increased postinduction hypotension, especially in patients over 70 years of age, but not 30-day mortality. IMPLICATIONS: Older patients received greater-than-recommended doses of propofol for induction, which may have led to significant dose-dependent hypotension. Despite this finding, the dose of propofol for induction was not independently associated with a greater 30-day mortality rate. More education regarding geriatric concerns is needed for encouraging anesthesiologists to tailor the plan for anesthesia in geriatric patients. However, overall postsurgical mortality is a function of preoperative risk and type surgical procedure. PMID- 26548322 TI - Non-statin Treatments for Managing LDL Cholesterol and Their Outcomes. AB - PURPOSE: Over the past 3 decades reducing LDL-C has proven to be the most reliable and easily achievable modifiable risk factor to decrease the rate of cardiovascular morbidity and mortality. Statins are effective, but problems with their side effects, adherence, or LDL-C efficacy in some patient groups remain. Most currently available alternative lipid-modifying therapies have limited efficacy or tolerability, and additional effective pharmacologic modalities to reduce LDL-C are needed. METHODS: Recent literature on new and evolving LDL-C lowering modalities in preclinical and clinical development was reviewed. FINDINGS: Several new therapies targeting LDL-C are in development. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a recently elucidated key regulator of plasma LDL-C, is the most promising and effective, with a number of approaches aimed at this target. The most advanced are monoclonal antibodies, which have demonstrated LDL-C reductions of ~60%, whether given alone or added to statins. Other PCSK9-targeted therapies in clinical development include adnectins and gene silencing techniques. Preclinical approaches involve vaccines, whereas a search remains for small molecule inhibitors. Other new pharmacologic approaches in Phase III clinical trials include a refocusing of cholesterol ester transfer protein inhibitors from primarily agents to increase HDL-C to their off-target effect on LDL-C and adenosine triphosphate citrate lyase inhibition. In earlier clinical development is new delivery of nicotinic acid-containing compounds. Additional agents are being developed as orphan indications expressly for patients with homozygous familial hypercholesterolemia, including peroxisome proliferator activated receptor-delta agonists, angiopoietin-like protein 3 inhibitors, and gene therapy. IMPLICATIONS: Monoclonal antibodies that inhibit PCSK9 were shown to be very effective reducers of LDL-C and well tolerated despite subcutaneous administration, and no significant safety issues have yet emerged during large Phase II and III trials. They have the potential to substantially impact further the risk of cardiovascular disease. A number of additional new, but less effective, oral LDL-C-lowering agents are also in various stages of development, including some which are targeted only to patients with homozygous familial hypercholesterolemia. PMID- 26548321 TI - Recommendations Concerning the Therapeutic Approach to Immunocompromised Children With Tuberculosis. AB - PURPOSE: This article describes the recommendations of a group of scientific societies concerning the therapeutic approach to immunocompromised children with tuberculosis (TB). METHODS: Using the Consensus Conference method, relevant publications in English were identified by a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until December 31, 2014. FINDINGS: On the basis of their clinical experience and the published evidence, the group of experts concluded that, although immunosuppressed subjects are at greater risk of developing TB, none of the signs or symptoms is sensitive or specific enough to enable a diagnosis. Immunocompromised patients are at greater risk of developing extrapulmonary forms of TB, especially if they are adolescents, whereas pulmonary forms are more prevalent among younger patients. When TB is suspected, a combination of skin and immunologic tests and other clinical, radiologic, and microbiologic examinations can be used to assess the risk of infection or disease. If the TB diagnosis is confirmed, immunocompromised children should be treated by using a standard regimen with a minimum of 4 drugs for at least 9 to 12 months, during which the tolerability of the drugs and their interactions should be carefully evaluated. IMPLICATIONS: It is difficult to diagnose and treat TB in immunocompromised children. Thus, all pediatric patients undergoing immunosuppressive therapy who develop TB should be diagnosed and treated at a TB reference center, which should also be responsible for the recommended follow-up. PMID- 26548323 TI - Contemporary and Novel Therapeutic Options for Hypertriglyceridemia. AB - PURPOSE: The purpose of this review was to outline the current and emerging therapeutic options for the treatment of hypertriglyceridemia, with an emphasis on emerging therapies. METHODS: A systematic literature search was conducted with the use of PubMed and Embase for articles on hypertriglyceridemia, with a focus on therapeutics, pharmacology, and management. Abstracts from recent international meetings were also reviewed for presentations of Phase I and II data on agents with triglyceride-lowering effects. A further review of the references identified from these articles was also performed. FINDINGS: Consistent with the multifactorial cause of hypertriglyceridemia, the therapeutic options are broad and numerous. This review explores the current and potential therapeutic options for treating hypertriglyceridemia and outlines the potential mechanisms of action. However, the mechanism of triglyceride reduction is complex, multifactorial, or not fully elucidated for some of these agents. The magnitude of triglyceride reduction and findings of outcome studies are described. IMPLICATIONS: Management of hypertriglyceridemia is about to enter an exciting phase, with multiple emerging therapies in the final stages of development. However, caution is warranted, because studies of therapeutic agents over the previous decade have often not found cardiovascular outcome benefits despite encouraging effects on triglyceride concentrations. PMID- 26548324 TI - Targeting High-density Lipoproteins to Reduce Cardiovascular Risk: What Is the Evidence? AB - PURPOSE: This article reviews therapies that affect HDLs. FINDINGS: Lipid modifying agents in current use (including statins, fibrates, and niacin) increase the concentration of HDL cholesterol to some extent. However, these agents have additional effects (beyond raising HDL) with the potential to reduce atherosclerotic cardiovascular disease (ASCVD) risk, making it difficult to determine (one way or the other) whether an increase in HDL concentration affects risk. New investigational approaches targeting HDLs include infusions of reconstituted HDLs, reinfusion of selectively delipidated plasma in which the concentration of pre-beta HDLs (the preferred acceptor of cell cholesterol) has been increased, and inhibitors of cholesteryl ester transfer protein (CETP). Positive results of the effects of reconstituted HDL infusions on coronary atheroma burden encourage further investigation of these agents. One small study on the effects of reinfusing selectively delipidated plasma has also provided results supporting additional development of this approach. CETP inhibitors are the most effective HDL-raising agents developed yet, with the ability to more than double the concentration of HDL cholesterol. They also reduce LDL cholesterol by up to 50%. Clinical outcome trials with the first 2 of these agents (torcetrapib and dalcetrapib) failed and, in the case of torcetrapib, treatment increased ASCVD events and increased both cardiovascular and noncardiovascular death. However, the subsequent discovery that torcetrapib had serious adverse effects unrelated to CETP inhibition meant that trials with this agent were unable to test the hypothesis that inhibiting CETP (or raising the level of HDL cholesterol) would translate into a reduction in ASCVD risk. The trial with dalcetrapib, a relatively weak inhibitor of CETP, was conducted in people soon after an acute coronary event when HDL functionality is impaired. The CETP inhibitor hypothesis will remain untested until completion of ongoing trials with CETP inhibitors that are more potent than dalcetrapib and that do not have the adverse effects of torcetrapib. IMPLICATIONS: Positive trials with reconstituted HDL infusions and reinfusions of selectively delipidated plasma will establish HDLs as important therapeutic targets. However, although a positive result in the trials with CETP inhibitors will establish CETP inhibition as a valid strategy to reduce ASCVD risk, it will not be possible to determine with certainty whether the reduction in risk is the consequence of effects on the HDL fraction or whether it is the result of CETP inhibitor-mediated reductions in LDL cholesterol. PMID- 26548326 TI - Validating pharmaceutical product claims: questions a formulary committee should ask. AB - Claims, justifying the acceptance and placement of new products on health system formularies, are all too often presented in terms that are either unverifiable or only verifiable in a timeframe that is of no practical benefit to formulary committees. One solution is for formulary committees to request that (i) all predictive claims made should be capable of empirical testing and (ii) manufacturers in making submissions should be asked to submit a protocol that details how their claims are to be assessed. Evaluation of claims can provide not only a significant input to ongoing disease area and therapeutic reviews, but can also provide a needed link to comparative effectiveness research and value-based healthcare. This paper presents a set of protocol standards (PROST) together will questions that should be addressed in a protocol review. PMID- 26548325 TI - The role of H4 flagella in Escherichia coli ST131 virulence. AB - Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug resistant clone associated with urinary tract and bloodstream infections. Most ST131 strains exhibit resistance to multiple antibiotics and cause infections associated with limited treatment options. The largest sub-clonal ST131 lineage is resistant to fluoroquinolones, contains the type 1 fimbriae fimH30 allele and expresses an H4 flagella antigen. Flagella are motility organelles that contribute to UPEC colonisation of the upper urinary tract. In this study, we examined the specific role of H4 flagella in ST131 motility and interaction with host epithelial and immune cells. We show that the majority of H4-positive ST131 strains are motile and are enriched for flagella expression during static pellicle growth. We also tested the role of H4 flagella in ST131 through the construction of specific mutants, over-expression strains and isogenic mutants that expressed alternative H1 and H7 flagellar subtypes. Overall, our results revealed that H4, H1 and H7 flagella possess conserved phenotypes with regards to motility, epithelial cell adhesion, invasion and uptake by macrophages. In contrast, H4 flagella trigger enhanced induction of the anti-inflammatory cytokine IL-10 compared to H1 and H7 flagella, a property that may contribute to ST131 fitness in the urinary tract. PMID- 26548327 TI - Case Report of a Synchronous Nipple Adenoma and Breast Carcinoma with Current Multi-modality Radiologic Imaging. AB - This case report presents the first reported molecular breast imaging appearance of a nipple adenoma coexisting with an ipsilateral breast malignancy. Conventional multi-modality radiologic imaging, including mammography, ultrasonography, and magnetic resonance imaging are also shown, and a brief review of the literature is provided. PMID- 26548328 TI - Photoguided Shape Deformation of Azobenzene-Containing Polymer Microparticles. AB - Here we present the generation of uniform microparticles with tunable diameters from azobenzene-based homopolymer by combining the microfluidics technique and emulsion-solvent evaporation route. In addition, the photoinduced deformation behavior of these microspheres, irradiated by a linearly polarized beam with different irradiation time and direction, are systemically studied. The deformation process through real time optical microscope observation can be investigated, benefiting from the uniform and microscaled size of the polymer particles. These results indicate that the deformation degree characterized by relative variation of the long axial for the particles can be controlled by the irradiation time. Moreover, elongated particles with tunable aspect ratio or tilted shape can be generated by manipulating the irradiation direction and/or time. Interestingly, the shape transformation kinetics displays a significant dependence on initial size of the polymer particle. In addition, the shape transformation of the polymer particle can lead to the variation of the orientation and distribution of the encapsulated anisotropic gold nanorods. PMID- 26548329 TI - Clinical applications of molecular genetic discoveries. AB - Genome-wide association studies of complex traits have mapped >15,000 common single nucleotide variants (SNVs). Likewise, applications of massively parallel nucleic acid sequencing technologies often referred to as next-generation sequencing to molecular genetic studies of complex traits have catalogued a large number of rare variants (population frequency of <0.01) in cases with complex traits. Moreover, high-throughput nucleic acid sequencing, variant burden analysis, and linkage studies are illuminating the presence of large number of SNVs in cases and families with single-gene disorders. The plethora of the genetic variants has exposed the formidable challenge of identifying the causal and pathogenic variants from the enormous number of innocuous common and rare variants that exist in the population and in an individual genome. The arduous task of identifying the causal and pathogenic variants is further compounded by the pleiotropic effects of the variants, complexity of cis and trans interactions in the genome, variability in phenotypic expression of the disease, as well as phenotypic plasticity, and the multifarious determinants of the phenotype. Population genetic studies offer the initial roadmaps and have the potential to elucidate novel pathways involved in the pathogenesis of the disease. However, the genome of an individual is unique, rendering unambiguous identification of the causal or pathogenic variant in a single individual exceedingly challenging. Yet, the focus of the practice of medicine is on the individual, as Sir William Osler elegantly expressed in his insightful quotation: "The good physician treats the disease; the great physician treats the patient who has the disease." The daunting task facing physicians, patients, and researchers alike is to apply the modern genetic discoveries to care of the individual with or at risk of the disease. PMID- 26548330 TI - Proprotein convertase subtilisin kexin type 9 and high-density lipoprotein metabolism: experimental animal models and clinical evidence. AB - Proprotein convertase subtilisin kexin type 9 (PCSK9) belongs to the proprotein convertase family. Several studies have demonstrated its involvement in the regulation of low-density lipoprotein (LDL) cholesterol levels by inducing the degradation of the LDL receptor (LDLR). However, experimental, epidemiologic, and pharmacologic data provide important evidence on the role of PCSK9 also on high density lipoproteins (HDLs). In mice, PCSK9 regulates the HDL cholesterol (HDL-C) levels by the degradation of hepatic LDLR, thus inhibiting the uptake of apolipoprotein (Apo)E-containing HDLs. Several epidemiologic and genetic studies reported positive relationship between PCSK9 and HDL-C levels, likely by reducing the uptake of the ApoE-containing HDL particles. PCSK9 enhances also the degradation of LDLR's closest family members, ApoE receptor 2, very low-density lipoprotein receptor, and LDLR-related protein 1. This feature provides a molecular mechanism by which PCSK9 may affect HDL metabolism. Experimental studies demonstrated that PCSK9 directly interacts with HDL by modulating PCSK9 self-assembly and its binding to the LDLR. Finally, the inhibition of PCSK9 by means of monoclonal antibodies directed to PCSK9 (ie, evolocumab and alirocumab) determines an increase of HDL-C fraction by 7% and 4.2%, respectively. Thus, the understanding of the role of PCSK9 on HDL metabolism needs to be elucidated with a particular focus on the effect of PCSK9 on HDL-mediated reverse cholesterol transport. PMID- 26548331 TI - The Directional Observation of Highly Dynamic Membrane Tubule Formation Induced by Engulfed Liposomes. AB - Highly dynamic tubular structures in cells are responsible for exchanges between organelles. Compared with bacterial invasion, the most affordable and least toxic lipids were found in this study to be gentle and safe exogenous stimuli for the triggering of membrane tubules. A specific lipid system was internalized by NIH3T3 cells. Following cellular uptake, the constructed liposomes traveled towards the nucleus in aggregations and were gradually distributed into moving vesicles and tubules in the cytosol. The triggered tubules proceeded, retreated or fluctuated along the cytoskeleton and were highly dynamic, moving quickly (up to several microns per second), and breaking and fusing frequently. These elongated tubules could also fuse with one another, giving rise to polygonal membrane networks. These lipid systems, with the novel property of accelerating intracellular transport, provide a new paradigm for investigating cellular dynamics. PMID- 26548332 TI - Regulation of oxidative response and extracellular polysaccharide synthesis by a diadenylate cyclase in Streptococcus mutans. AB - Cyclic diadenosine monophosphate (c-di-AMP) has been implicated in the control of many important bacterial activities. However, the function of this molecule in Streptococcus mutans, the primary aetiological agent of human dental caries, is unknown. In this study, we identified and characterized a diadenylate cyclase, named CdaA, in S. mutans. Furthermore, we showed that in-frame deletion of the cdaA gene in S. mutans causes decreased c-di-AMP levels, increased sensitivity to hydrogen peroxide and increased production of extracellular polysaccharides. Global gene expression profiling revealed that more than 200 genes were significantly upregulated or downregulated (> 2.0-fold) in the cdaA mutant. Interestingly, genes with increased or decreased expression were clustered in cellular polysaccharide biosynthetic processes and oxidoreductase activity respectively. Notably, the expression of several genomic islands, such as GTF B/C, TnSmu, CRISPR1-Cas and CRISPR2-Cas, was found to be altered in the cdaA mutant, indicating a possible link between these genomic islands and c-di-AMP signalling. Collectively, the results reported here show that CdaA is an important global modulator in S. mutans and is required for optimal growth and environmental adaption. This report also paves the way to unveil further the roles of c-di-AMP signalling networks in the biology and pathogenicity of S. mutans. PMID- 26548334 TI - Sensitivity of human embryonic stem cells to different conditions during cryopreservation. AB - Low cell recovery rate of human embryonic stem cells (hESCs) resulting from cryopreservation damages leads to the difficulty in their successful commercialization of clinical applications. Hence in this study, sensitivity of human embryonic stem cells (hESCs) to different cooling rates, ice seeding and cryoprotective agent (CPA) types was compared and cell viability and recovery after cryopreservation under different cooling conditions were assessed. Both extracellular and intracellular ice formation were observed. Reactive oxidative species (ROS) accumulation of hESCs was determined. Cryopreservation of hESCs at 1 degrees C/min with the ice seeding and at the theoretically predicted optimal cooling rate (TPOCR) led to lower level of intracellular ROS, and prevented irregular and big ice clump formation compared with cryopreservation at 1 degrees C/min. This strategy further resulted in a significant increase in the hESC recovery when glycerol and 1,2-propanediol were used as the CPAs, but no increase for Me2SO. hESCs after cryopreservation under all the tested conditions still maintained their pluripotency. Our results provide guidance for improving the hESC cryopreservation recovery through the combination of CPA type, cooling rate and ice seeding. PMID- 26548335 TI - Cryogenic 3D printing for tissue engineering. AB - We describe a new cryogenic 3D printing technology for freezing hydrogels, with a potential impact to tissue engineering. We show that complex frozen hydrogel structures can be generated when the 3D object is printed immersed in a liquid coolant (liquid nitrogen), whose upper surface is maintained at the same level as the highest deposited layer of the object. This novel approach ensures that the process of freezing is controlled precisely, and that already printed frozen layers remain at a constant temperature. We describe the device and present results which illustrate the potential of the new technology. PMID- 26548336 TI - Probiotics: a proactive approach to health. A symposium report. AB - This report summarises talks given at the 8th International Yakult Symposium, held on 23-24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small intestine as a probiotic target and inclusion of probiotics into integrative approaches to gastroenterology. Probiotic recommendations in gastroenterology guidelines and current data on probiotic efficacy in paediatric patients were reviewed. Updates were given on probiotic and gut microbiota research in obesity and obesity-related diseases, the gut-brain axis and development of psychobiotics, and the protective effects of equol-producing strains for prostate cancer. Recent studies were presented on probiotic benefit for antibiotic-associated diarrhoea and people with HIV, as well as protection against the adverse effects of a short-term high-fat diet. Aspects of probiotic mechanisms of activity were discussed, including immunomodulatory mechanisms and metabolite effects, the anti-inflammatory properties of Faecalibacterium prausnitzii, the relationship between periodontitis, microbial production of butyrate in the oral cavity and ageing, and the pathogenic mechanisms of Campylobacter. Finally, an insight was given on a recent expert meeting, which re-examined the probiotic definition, advised on the appropriate use and scope of the term and outlined different probiotic categories and the prevalence of different mechanisms of activity. PMID- 26548338 TI - Hydrogen bonding plays a significant role in the binding of coomassie brilliant blue-R to hemoglobin: FT-IR, fluorescence and molecular dynamics studies. AB - An analog of coomassie brilliant blue-R (CBB-R) was recently found to act as an antagonist to ATP-sensitive purinergic receptors (P2X7R) and has potential to be used in medicine. With the aim of understanding its transportation and distribution through blood, in this investigation, we measured the binding parameters of CBB-R with bovine hemoglobin (BHG). The molecule specifically bound to a single binding site of the protein with a stoichiometric ratio of 1 : 1 and the observed binding constant Ka was 3.5, 2.5, 2.0 and 1.5 * 10(5) M(-1) at 20 degrees C, 27 degrees C, 37 degrees C and 45 degrees C, respectively. The measured respective DeltaG(0) values of the binding at four temperatures were 30.45, -22.44, -18.04 and -11.95 kJ mol(-1). The DeltaH(0) (change in enthalpy) and DeltaS(0) (change in entropy) values were -23.6 kJ mol(-1) and -70.66 J mol( 1) respectively in the binding process. The negative value of DeltaH(0) and DeltaS(0) indicated that the binding of the molecule was thermodynamically favorable. The best energy structure in the molecular docking analysis revealed that CBB-R preferred to be intercalated in the cavity among the alpha2, beta1 and beta2 subunits and the binding location was 7.4 A away from Trp37 in the beta2 subunit. The binding of the molecule with the protein was stabilized by hydrogen bonds involving the side chain of two amino acid residues. The residues were Lys104 and Glu101 in the beta2 subunit. The binding was further stabilized via hydrogen bond formation between the amide group of the peptide backbone (residue Tyr145 of the beta1 subunit) and CBB-R. A shift of the amide I (-C=O stretching) band frequency of ~8 cm(-1) to low energy was ascribed to the hydrogen bond interaction involving the polypeptide carbonyl of the protein and the CBB-R molecule. In addition, two pi-cation interactions between Lys99 of the alpha2 subunit and Lys104 of the beta2 subunit and CBB-R contributed favorably in the binding processes. No substantial change in the soret and Q absorption bands of BHG could be observed in the presence of CBB-R. It indicated that the oxygen binding domain or the heme proximity was not blocked or substantially perturbed due to the binding of CBB-R. The circular dichroism and the molecular dynamics analysis further established that the binding interaction caused no significant alteration in the protein long range secondary structure. PMID- 26548337 TI - Chronic Stress Alters Spatial Representation and Bursting Patterns of Place Cells in Behaving Mice. AB - Chronic uncontrollable stress has been shown to produce various physiological alterations and impair mnemonic functions in the rodent hippocampus. Impacts on neuronal activities, however, have not been well investigated. The present study examined dorsal CA1 place cells to elucidate the computational changes associated with chronic stress effects on cognitive behaviors. After administering chronic restraint stress (CRS; 6 hours/day for >=21 consecutive days) to adult male mice, several hippocampal characteristics were examined; i.e., spatial learning, in vitro synaptic plasticity, in vivo place cell recording, and western blot analysis to determine protein levels related to learning and memory. Behaviorally, CRS significantly impeded spatial learning but enhanced non-spatial cue learning on the Morris water maze. Physiologically, CRS reduced long-term potentiation (LTP) of Schaffer collateral/commisural-CA1 pathway, phospho alphaCaMKII (alpha Ca2(+)/calmodulin-dependent protein kinase II) level in the hippocampus, and stability of spatial representation and the mean firing rates (FRs) of place cells. Moreover, the local cue-dependency of place fields was increased, and the intra-burst interval (IntraBI) between consecutive spikes within a burst was prolonged following CRS. These results extend the previous findings of stress impairing LTP and spatial learning to CRS modifying physical properties of spiking in place cells that contribute to changes in navigation and synaptic plasticity. PMID- 26548339 TI - Rapid Sample Preparation Methodology for Plant N-Glycan Analysis Using Acid Stable PNGase H+. AB - The quantification of potentially allergenic carbohydrate motifs of plant and insect glycoproteins is increasingly important in biotechnological and agricultural applications as a result of the use of insect cell-based expression systems and transgenic plants. The need to analyze N-glycan moieties in a highly parallel manner inspired us to develop a quick N-glycan analysis method based on a recently discovered bacterial protein N-glycanase (PNGase H(+)). In contrast to the traditionally used PNGase A, which is isolated from almond seeds and only releases N-glycans from proteolytically derived glycopeptides, the herein implemented PNGase H(+) allows for the release of N-glycans directly from the glycoprotein samples. Because PNGase H(+) is highly active under acidic conditions, the consecutive fluorescence labeling step using 2-aminobenzamide (2AB) can be directly performed in the same mixture used for the enzymatic deglycosylation step. All sample handling and incubation steps can be performed in less than 4 h and are compatible with microwell-plate sampling, without the need for tedious centrifugation, precipitation, or sample-transfer steps. The versatility of this methodology was evaluated by analyzing glycoproteins derived from various plant sources using ultra-performance liquid chromatography (UPLC) analysis and further demonstrated through the activity analysis of four PNGase H(+) mutant variants. PMID- 26548340 TI - Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPARgamma and downregulating MMP-9 expression. AB - The mortality rate of ovarian cancer is the highest of all gynecological malignancies. Telmisartan is a commonly used clinical angiotensin receptor blocker, which has antihypertensive, anti-inflammatory and antithrombotic effects. In the present study, it was investigated whether telmisartan could exert anticancer effects on ovarian cancer cells through upregulating peroxisome proliferator-activated receptor gamma (PPARgamma) and downregulating matrix metalloproteinase-9 (MMP-9) expression. A 3.3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay was conducted to analyze the proliferation of HEY cells. A Caspase-3 Activity Assay kit and an Annexin V-fluorescein isothiocyanate/propidium iodide kit were used to analyze the apoptosis of HEY cells. In addition, a gelatin zymography assay and reverse trancription quantitative polymerase chain reaction were included to analyze the expression of PPARgamma and MMP-9 in HEY cells. The data showed that telmisartan could significantly decrease cell viability and induce the apoptosis of HEY cells in a time- and dose-dependent manner. Furthermore, telmisartan could also dose dependently increase the expression of PPARgamma and decrease the expression of MMP-9 in HEY cells. In addition, downregulation of the expression of PPARgamma by small interfering (si)RNA could reduce the effect of telmisartan on ovarian cancer cells and increase the expression of MMP-9. In conclusion, the results indicated that telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells by upregulating PPARgamma and downregulating MMP-9 expression. PMID- 26548341 TI - Adherence to an Aerobic Exercise Intervention after an Implantable Cardioverter Defibrillator (ICD). AB - BACKGROUND: Exercise adherence is an important element in achieving important exercise outcomes. The purpose of this study was to describe adherence in a home based aerobic exercise program following an implantable cardioverter defibrillator (ICD), determine effects of adherence on peakVO2 , and outline reasons for nonadherence. METHODS AND RESULTS: A single-blind randomized control trial of home walking compared to usual care in 160 patients with an ICD for primary or secondary prevention was conducted. This report is on adherence in the exercise arm (N = 84). Home walking exercise consisted of 8 weeks of aerobic conditioning (60 minutes/day, 5 days/week) followed by 16 weeks of aerobic maintenance (150 minutes/week, 30 minutes/session) at 60-80% of heart rate reserve. Adherence was tracked using Polar heart rate (HR) monitors, pedometers, home exercise logs, and telephone follow-up. Adherence was defined as performing at least 80% of prescribed exercise. For aerobic conditioning, there was a mean frequency of 3.81 walks/week, duration of 1,873 minutes walked, and 17.5% of exercise was in the target HR (THR) zone. For aerobic maintenance, there was a mean frequency of 2.4 walks/week, duration of 1,872 minutes/walked, and 8.7% of exercise was in the THR zone. Those who were 80% adherent achieved a 3.4 mL/kg/min (P = 0.03) improvement in peakVO2 over those who were <80% adherent. Reasons for nonadherence to exercise ranged from scheduling issues to viral illness and fatigue. CONCLUSIONS: Adherence to aerobic exercise frequency and duration was high with few dropouts, resulting in higher peakVO2 . Exercise monitoring equipment encouraged adherence and conferred a sense of safety to exercise. PMID- 26548342 TI - Prognostic value of psychological state in cochlear implantation. AB - CONCLUSION: Perioperative Minnesota Multiphasic Personality Inventory (MMPI) scores may be beneficial for predicting prognosis of cochlear implantation (CI). A positive attitude for social interaction in particular correlates with a better speech outcome. Proper perioperative psychological management may, therefore, assist in the auditory rehabilitation of CI patients. OBJECTIVE: To determine the perioperative psychological state of CI patients and its relationship with patient prognosis after CI. METHODS: This study prospectively enrolled 29 patients who underwent CI from 2005-2013. The MMPI was administered to assess psychosocial and emotional issues surrounding CI and the Korean version of the Central Institute of Deafness (K-CID) score was used to measure speech perception. RESULTS: CI resulted in a significant improvement on the MMPI Paranoia scale (p = 0.02). Patients with abnormal pre-operative and post operative MMPI scores also had an earlier onset of deafness, longer duration of deafness, and lower K-CID scores than patients with normal MMPI scores (all p < 0.05). The post-CI K-CID score had a significant negative correlation with the pre-operative MMPI Schizophrenia score (p < 0.01) and significant negative correlations with the post-operative MMPI Paranoia (p = 0.02), Psychasthenia (p = 0.02), Schizophrenia (p = 0.04), Hypomania (p = 0.02) and Social Introversion (p = 0.03) scores. PMID- 26548343 TI - Immunomodulatory and neuroprotective effects of ginsenoside Rg1 in the MPTP(1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine) -induced mouse model of Parkinson's disease. AB - Ginsenoside Rg1, one of the biologically active ingredients of ginseng, has been considered to be a candidate neuroprotective drug. The objective of the study was to study the protective effects of Rg1 through the peripheral and central inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Rg1 treatment protected TH-positive cells in the SNpc region from MPTP toxicity measured with immunofluoresence. The protein expression levels of TH in the SNpc region of MPTP-induced mice following treatment with Rg1 were higher than MPTP-induced mice which were tested with Western blot. The ratio of CD3(+)CD4(+) to CD3(+)CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells in the blood increased in MPTP-induced mice following treatment with Rg1 which were detected by flow cytometry analysis. Moreover, Rg1 reduced the serum concentrations of proinflammatory cytokines TNF alpha, IFN-gamma, IL-1beta and IL-6 which were tested with enzyme-linked immunosorbent assay (ELISA). In addition, Rg1 inhibited the activation of microglia and reduced the infiltration of CD3(+) T cells into the SNpc region which were measured by immunofluorescence. Our results indicated that Rg1 may represent a promising drug for the treatment of PD via the regulation of the peripheral and central inflammation. PMID- 26548344 TI - Baicalein inhibits hepatocellular carcinoma cells through suppressing the expression of CD24. AB - Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and is the most common type of liver cancer. Current therapies for hepatocellular carcinoma are still rather limited and novel therapeutic strategies are required. Baicalein, extracted from Scutellaria baicalensis, has anticancer effects on HCC in vitro and vivo. However, the detailed mechanisms are not well studied yet. In the present study, we evaluated anticancer effects of purified botanical extracts on HCC cells using high-throughput screening and investigated the effects of baicalein on HCC cells using proliferation and apoptosis assays, RT-PCR, and Western blot. Transfection was used to explore the underlying mechanisms of these effects. Our results showed that baicalein is the most efficient botanical extract in a HCC cell line as compared with the other 13 extracts. Baicalein significantly decreased the expression of c-Myc, a crucial regulator of cell proliferation, apoptosis and cellular transformation, in dose- and time-dependent manners in HCC cells. Moreover, baicalein inhibited HCC cell proliferation and induced apoptosis. The mRNA and protein expressions of CD24 were downregulated by baicalein in HCC cells and ectopic overexpression of CD24 reversed baicalein induced inhibition of cell proliferation and survival. Taken together, our results demonstrate efficient anticancer effects of baicalein on HCC cells and indicate that baicalein suppresses cell growth and cell survival through downregulation of CD24. PMID- 26548345 TI - Ginseng marc-derived low-molecular weight oligosaccharide inhibits the growth of skin melanoma cells via activation of RAW264.7 cells. AB - Panax ginseng C.A. Meyer has been traditionally consumed to prevent or treat various medical disorders due to its diverse health benefits. Polysaccharides isolated from Panax ginseng have been known to possess various pharmacological activities, including immune modulating, anti-diabetic, and anti-obesity properties. Despite the increasing number of reports on the bioactivities of ginseng polysaccharides, little is known regarding the medicinal potential of ginseng-derived oligosaccharides. In this study, we prepared a lower-molecular weight oligosaccharide (GOS, MW. 2.2kDa) from ginseng polysaccharides (MW. 11 605kDa) by enzymatic degradation and evaluated for its immunostimulating activities in RAW 264.7 murine macrophage cells. GOS was shown to be a glucan type oligosaccharide mainly containing glucose residues (97.48 in molar %). Treatment with GOS (100-500MUg/ml) dose-dependently enhanced the production of TNF-alpha, IL-6, and NO in RAW 264.7 cells. Western blot analysis indicated that GOS dose-dependently induced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and nuclear factor kappaB (NFkappaB), which are upstream signalling molecules for cytokine production. While GOS was not cytotoxic to the RAW 264.7 macrophage cells at the concentration tested (up to 1000MUg/ml), when B16F10 melanoma cells were co cultured with the GOS-activated macrophages, the cell viability of melanoma cells was dose-dependently decreased through the induction of apoptotic cell death. Taken together, these results suggested that ginseng marc-derived GOS has anti cancer activity in vitro against melanoma cells by potentiating macrophage function. PMID- 26548346 TI - Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis. AB - Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1beta, IL-2Ralpha, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis. PMID- 26548347 TI - Diallyl trisulfide inhibits naphthalene-induced oxidative injury and the production of inflammatory responses in A549 cells and mice. AB - Diallyl trisulfide (DATS) is a garlic organosulfide that may have a therapeutic potential in the treatment of some diseases. We sought to determine whether DATS could inhibit naphthalene-induced oxidative injury and the production of inflammatory responses in vitro and in vivo. A549 cells were either pre-treated (PreTx, prevention) or concurrently treated (CoTx, treatment) with 20MUM naphthalene and either 5 or 10MUM DATS. PreTx and CoTx showed the prevention and the treatment potential of DATS to inhibit the generation of naphthalene-induced reactive oxygen species (ROS) in the A549 cells. DATS showed antioxidative activity by elevating the SOD activities in the low dose groups. The mechanistic study showed that the DATS-mediated inhibition of naphthalene-induced oxidative injury and the production of inflammatory responses (i.e., TNF-alpha, IL-6, and IL-8) were attributed to inhibiting the activity of nuclear factor-kappa B (NF kappaB). In addition, DATS inhibited the production of serum nitric oxide NO and myeloperoxidase (MPO) in the lungs of Kunming mice. The histological analysis results indicate that DATS inhibited the naphthalene-induced lung damage, which is consistent with the in vitro study results. The in vivo and in vitro results suggest that DATS may be an effective attenuator of naphthalene-induced lung damage. PMID- 26548348 TI - Pristimerin inhibits angiogenesis in adjuvant-induced arthritic rats by suppressing VEGFR2 signaling pathways. AB - Rheumatoid arthritis (RA) is a progressive, inflammatory autoimmune disease. As RA progresses, the hyperplastic synovial pannus creates a hypoxic, inflammatory environment that induces angiogenesis. Further vascularization of the synovial tissue promotes pannus growth and continued infiltration of inflammatory leukocytes, thus perpetuating the disease. Pristimerin inhibits inflammation and tumor angiogenesis. The present study focused on the inhibition of angiogenesis by Pristimerin in adjuvant-induced arthritic rats and the underlying molecular mechanisms. Our results clearly demonstrate for the first time that Pristimerin significantly reduces vessel density in synovial membrane tissues of inflamed joints and reduces the expression of pro-angiogenic factors in sera, including TNF-alpha, Ang-1, and MMP-9. Pristimerin also decreased the expression of VEGF and p-VEGFR2 in the synovial membrane, whereas the total amount of VEGFR2 remained unchanged. Pristimerin suppressed the sprouting vessels of the aortic ring and inhibited VEGF-induced HFLS-RA migration in vitro. Pristimerin also inhibited VEGF-induced proliferation, migration and tube formation by HUVECs, blocked the autophosphorylation of VEGF-induced VEGFR2 and consequently downregulated the signaling pathways of activated PI3K, AKT, mTOR, ERK1/2, JNK, and p38 in VEGF-induced HUVECs. Our results indicate that Pristimerin suppressed synovial angiogenesis in our rat model and in vitro by interrupting the targeting of VEGFR2 activation. Therefore, Pristimerin has potential as an angiogenesis inhibitor in the treatment of rheumatoid arthritis. PMID- 26548349 TI - Cefdinir nanosuspension for improved oral bioavailability by media milling technique: formulation, characterization and in vitro-in vivo evaluations. AB - Cefdinir (Cef) is an orally active Biopharmaceutics Classification System (BCS) class IV drug with incomplete absorption and low bioavailability (16-21%). The aim of this investigation was to develop nanosuspensions (NS) of Cef to improve its oral bioavailability. Cef NS were prepared by the media milling technique using zirconium oxide beads as the milling media. Cef NS were characterized by particle size, Scanning Electron Microscopy, Differential Scanning Calorimetry, X Ray Diffraction pattern and evaluated for saturation solubility, in vitro release studies, ex vivo permeability studies and in vivo bioavailability studies. The particle size and zeta potential were found to be 224.2 +/- 2.7 nm and -15.7 +/- 1.9 mV, respectively. Saturation solubility of NS was found to be 1985.3 +/- 10.2 ug/ml which was 5.64 times higher than pure drug (352.2 +/- 6.5 ug/ml). The DSC thermograms and XRD patterns indicated that there was no interaction between drug and excipients and that the crystallinity of Cef remained unchanged after media milling process. Results of in vitro release studies and ex vivo permeation studies showed improved drug release of 88.2 1 +/- 2.90 and 83.11 +/- 2.14%, respectively, from NS after 24 h as compared to drug release of 54.09 +/- 2.54 and 48.2 1 +/- 1.27%, respectively, from the marketed suspension (Adcef). In vivo studies in rats demonstrated a 3-fold increase in oral bioavailability from the NS in comparison to marketed suspension. The results of this investigation conclusively show that the developed nanosuspension of Cef exhibited improved solubility, dissolution and permeation which led to a significant enhancement in its oral bioavailability. PMID- 26548350 TI - Nanoparticles as drug carriers: current issues with in vitro testing. AB - Incorporation of nanotechnology in the field of drug delivery has created exciting opportunities for the purposeful design of nanocarriers with potentials such as targeted delivery or controlled release of the incorporated cargo, improvement of bioavailability and reduction of therapeutic side-effects. Prior to in vivo administration, nanocarriers should undergo a set of in vitro evaluation procedures to ensure their stability, safety, conformity and ability to fulfill the desired mission. In this paper, current issues with in vitro evaluation techniques used for nanocarrier characterization (assessment of particle size, surface charge, drug release and toxicity) will be discussed. Furthermore, sufficiency of in vitro evaluation procedures for the prediction of in vivo scenarios and the necessary considerations to improve the correlation between the two settings will be debated. PMID- 26548351 TI - Higher relatedness mitigates mortality in a nematode with lethal male fighting. AB - According to kin selection theory, individuals show less aggression towards their relatives. Limited dispersal promotes interactions among relatives but also increases competition among them. The evolution of cooperation in viscous populations has been subject of mainly theoretical exploration. We investigated the influence of relatedness on aggression in males of entomopathogenic nematode Steinernema longicaudum that engage in lethal fighting. In a series of in vitro experiments, we found that both competitor male group size and relatedness influence male mortality rates. Higher relatedness led to progressively lower rates of male mortality. In experimentally infected insects, wherein large numbers of males and females interact, the proportion of dead and paralysed (= terminally injured) males was higher when infection was established by infective juveniles originating from a mixture of three lines than in those infected by a single line. The results collectively show that Steinernema longicaudum males recognize their kin and consequently male mortality rates are lower in groups consisting of more related males. Furthermore, this monotonic negative relationship between aggression and relatedness suggests that kin selection benefits are still substantial even under extreme competition. Our experiments also suggest that kin recognition in entomopathogenic nematodes has a genetic basis rather than being strictly based on environmental cues. We discuss our findings within the theoretical context of the evolution of altruistic/cooperative behaviour in structured populations. PMID- 26548352 TI - An observational comparison of the older and younger bus passenger experience in a developing world city. AB - This study was an unobtrusive observational analysis of 333 older and younger bus passengers in Guadalajara, Mexico. A set of data were collected for each observed passenger, as well as more general observations related to driver behaviour, bus design and bus service characteristics. There were significant differences between older and younger passengers in terms of boarding and alighting times, use of handrails, seat location preferences, passenger stability and coping strategies in order to maintain postural stability. The conditions of travel are conducive to a poor passenger experience for the older passengers in particular. Although the problems may be attributed to bus design and driver behaviour typical of that in developing countries, they are also influenced by the wider transport infrastructure, and a lack of a regulatory regime which places drivers under time pressure and in direct competition with each other. Practitioner Summary: Bus services must cater for all ages of passengers, including the elderly. This unobtrusive observational study investigated the passenger experience in a developing world city. Bus and wider service design were found to compromise the journey experience, with the older users being particularly negatively impacted. Design recommendations are provided. PMID- 26548353 TI - Development of Fluorescent Protein Probes Specific for Parallel DNA and RNA G Quadruplexes. AB - We have developed fluorescent protein probes specific for parallel G-quadruplexes by attaching cyan fluorescent protein to the G-quadruplex-binding motif of the RNA helicase RHAU. Fluorescent probes containing RHAU peptide fragments of different lengths were constructed, and their binding to G-quadruplexes was characterized. The selective recognition and discrimination of G-quadruplex topologies by the fluorescent protein probes was easily detected by the naked eye or by conventional gel imaging. PMID- 26548354 TI - Association of Energy Intake With the Lack of in-Person Review of Household Dietary Records: Analysis of Japan National Health and Nutrition Surveys From 1997 to 2011. AB - BACKGROUND: National surveys have demonstrated a long-term decrease in mean energy intake in Japan, despite the absence of a decrease in the prevalence of overweight and obesity. We aimed to examine whether total energy intake of survey respondents is associated with completion of an in-person review of dietary records and whether it affects the trend in mean energy intake. METHODS: We pooled data from individuals aged 20-89 years from the National Nutrition Surveys of 1997-2002 and the National Health and Nutrition Surveys of 2003-2011. We conducted a linear mixed-effects regression to estimate the association between total energy intake and the lack of an in-person review of semi-weighed household dietary records with interviewers. As some respondents did not have their dietary data confirmed, we used regression coefficients to correct their total energy intake. RESULTS: Compared with respondents completing an in-person review, total energy intake was significantly inversely associated with respondents not completing a review across all sex and age groups (P < 0.001). After correction of total energy intake for those not completing a review, mean energy intake in each survey year significantly increased by 2.1%-3.9% in men and 1.3%-2.6% in women (P < 0.001), but the decreasing trend in mean energy intake was sustained. CONCLUSIONS: Total energy intake may be underestimated without an in-person review of dietary records. Further efforts to facilitate completion of a review may improve accuracy of these data. However, the increasing proportion of respondents missing an in-person review had little impact on the decreasing mean caloric intake. PMID- 26548355 TI - Effects of the Cessation of Mass Screening for Neuroblastoma at 6 Months of Age: A Population-Based Study in Osaka, Japan. AB - BACKGROUND: In 2004, the Japanese government halted the 6-month mass screening program for neuroblastoma. We investigated whether its cessation had led to an increase not only in mortality due to this disease but also in the incidence of advanced-stage disease among older children. METHODS: Study subjects were neuroblastoma patients retrieved from the population-based Osaka Cancer Registry. Trends of incidence and mortality from neuroblastoma were analyzed by calendar year and birth cohort. Prognostic factors, including stage and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) oncogene status, were compared before and after the cessation of mass screening. RESULTS: Age-standardized incidence rates in 2005-2009 (the cessation period of mass screening; 11.1 per million) were similar to those in 1975-1979 (the pre screening period; 8.6 per million). Age-standardized mortality rates tended to decrease from 1975-1979 (4.0 per million) to 2005-2009 (2.7 per million) in parallel with the improvement in survival. Analysis by birth cohort indicated that the mortality rates in 2004-2005 (after cessation) for children 0-4 years of age were lower than those in 1975-1979 (O:E ratio 0.25; 95% confidence interval, 0.03-0.90). For children 1-9 years of age, there was a not significant difference in the distribution of stage, MYCN oncogene status, and DNA ploidy between 1991 2003 (the mass screening period) and 2004-2008 (after cessation). CONCLUSIONS: The cessation of mass screening for neuroblastoma does not appear to have increased mortality due to this disease or incidence of advanced-stage disease among older children. PMID- 26548358 TI - Amine neurotransmitters, inflammation and epithelial sodium transport. AB - NEW FINDINGS: What is the topic of this review? The present work reviews the roles of renal and intestinal dopamine and 5-HT in the maintenance of fluid and electrolyte homeostasis. The role of inflammatory agents at the intestinal level that affect fluid and electrolyte homeostasis is also addressed. What advances does it highlight? General mechanisms of epithelial cell ion transport in the gastrointestinal tract and kidney share considerable similarities, particularly with regard to basolateral Na(+) ,K(+-) ATPase as a driving force for the movement of numerous substrates across the cell membrane. The physiological importance of the renal actions of monoamines (dopamine, noradrenaline and 5-HT) mainly depends on the sources of the amines in the kidney and on their availability to activate the amine-specific receptors. Dopamine and 5-HT are also relatively abundant in the mucosal cell layer of the intestine, and recent evidence suggests their physiological relevance in regulating electrolyte transport. The gastrointestinal tract can be an important site for the loss of water and electrolytes, in the presence of intestinal inflammation. General mechanisms of epithelial cell ion transport in the gastrointestinal tract and kidney share considerable similarities with regard to basolateral Na(+) ,K(+) ATPase as a driving force for the movement of numerous substrates across the cell membrane. The present work reviews the roles of renal and intestinal dopamine and 5-HT in the maintenance of fluid and electrolyte homeostasis. The role of inflammatory agents at the intestinal level that affect fluid and electrolyte homeostasis is also addressed. PMID- 26548359 TI - Juvenile Incarceration and Health. AB - Addressing the health status and needs of incarcerated youth represents an issue at the nexus of juvenile justice reform and health care reform. Incarcerated youth face disproportionately higher morbidity and higher mortality compared to the general adolescent population. Dental health, reproductive health, and mental health needs are particularly high, likely as a result of lower access to care, engagement in high-risk behaviors, and underlying health disparities. Violence exposure and injury also contribute to the health disparities seen in this population. Further, juvenile incarceration itself is an important determinant of health. Juvenile incarceration likely correlates with worse health and social functioning across the life course. Correctional health care facilities allow time for providers to address the unmet physical and mental health needs seen in this population. Yet substantial challenges to care delivery in detention facilities exist and quality of care in detention facilities varies widely. Community-based pediatricians can serve a vital role in ensuring continuity of care in the postdetention period and linking youth to services that can potentially prevent juvenile offending. Pediatricians who succeed in understanding and addressing the underlying social contexts of their patients' lives can have tremendous impact in improving the life trajectories of these vulnerable youth. Opportunities exist in clinical care, research, medical education, policy, and advocacy for pediatricians to lead change and improve the health status of youth involved in the juvenile justice system. PMID- 26548357 TI - Recent advances in understanding xenotransplantation: implications for the clinic. AB - The results of organ and cell allotransplantation continue to improve, but the field remains limited by a lack of deceased donor organs. Xenotransplantation, for example, between pig and human, offers unlimited organs and cells for clinical transplantation. The immune barriers include a strong innate immune response in addition to the adaptive T-cell response. The innate response has largely been overcome by the transplantation of organs from pigs with genetic modifications that protect their tissues from this response. T-cell-mediated rejection can be controlled by immunosuppressive agents that inhibit costimulation. Coagulation dysfunction between the pig and primate remains problematic but is being overcome by the transplantation of organs from pigs that express human coagulation-regulatory proteins. The remaining barriers will be resolved by the introduction of novel genetically-engineered pigs. Limited clinical trials of pig islet and corneal transplantation are already underway. PMID- 26548360 TI - Inability to acquire spatial information and deploy spatial search strategies in mice with lesions in dorsomedial striatum. AB - Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum. PMID- 26548356 TI - The role of lymphocytes in the development and treatment of alopecia areata. AB - Alopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri- and intra-follicular regions, and hair follicle disruption. Both CD4(+) and CD8(+) lymphocytes are abundant in AA lesions; however, CD8(+) cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8(+) cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the self-antigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8(+) cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches. PMID- 26548361 TI - The impact of different emotional states on the memory for what, where and when features of specific events. AB - Emotions can modulate the encoding and recollection of personal events. In the present study, we investigated the effects of different emotional states (pleasant, neutral or anxious) on episodic memory formation in a virtual reality (VR) setting. Emotional states were induced by pleasant, neutral or anxiety inducing movie clips prior to the presentation of specific events in a VR scenario. Episodic memory performance of healthy participants in whom an anxious emotional state had been induced was inferior to those of the neutral and pleasant conditions. In the anxious condition, participants were particularly impaired regarding their memory for the location of events. A correlational analysis indicated that high levels of negative arousal were associated with poor memory for the temporal and spatial context of events. In contrast, high levels of happiness were associated with better memory for the spatial context of events. Our data provide evidence that emotional arousal can modulate memory for what happened, where and when. PMID- 26548363 TI - [French National Academy of Medicine welcomes in Paris the first Mexican-French Forum in Health]. PMID- 26548364 TI - ADHD and Marijuana-Use Expectancies in Young Adulthood. AB - OBJECTIVE: This study examined mean level differences in marijuana expectancies and the differential associations between expectancies and marijuana use for individuals with and without a history of Attention-Deficit/Hyperactivity Disorder (ADHD). BACKGROUND: Substance-use expectancies are a widely studied risk factor for alcohol and other drug use. The relations between marijuana-use expectancies and self-reported marijuana use have not been examined in young adults with ADHD, a population shown to be at risk for marijuana use. METHOD: Participants were 306 (190 ADHD and 116 non-ADHD) young adults (M age = 20.06, SD = 2.03) from the Pittsburgh ADHD Longitudinal Study (PALS) who provided data about marijuana use and marijuana-use expectancies. RESULTS: Individuals in the ADHD group reported lower levels of social enhancement, tension reduction, and cognitive and behavioral-impairment expectancies compared to individuals in the non-ADHD group. Positive and negative marijuana-use expectancies were associated with marijuana use frequency in the whole sample and statistically significant ADHD group by expectancy interactions were found. Sexual-enhancement expectancies were more strongly associated with marijuana use frequency among individuals with ADHD histories while cognitive behavioral-impairment expectancies were more strongly associated with marijuana use frequency among individuals without ADHD. CONCLUSIONS: Marijuana-use expectancies may be acquired, and operate differently, for individuals with and without ADHD histories. Although future research is needed to test this speculation, these differences may be associated with ADHD related difficulties in higher order cognitive processes that affect the encoding and utilization of expectations regarding marijuana's effects. PMID- 26548362 TI - Development and function of the midbrain dopamine system: what we know and what we need to. AB - The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study. PMID- 26548365 TI - Aminobenzimidazoles and Structural Isomers as Templates for Dual-Acting Butyrylcholinesterase Inhibitors and hCB2 R Ligands To Combat Neurodegenerative Disorders. AB - A pharmacophore model for butyrylcholinesterase (BChE) inhibitors was applied to a human cannabinoid subtype 2 receptor (hCB2 R) agonist and verified it as a first-generation lead for respective dual-acting compounds. The design, synthesis, and pharmacological evaluation of various derivatives led to the identification of aminobenzimidazoles as second-generation leads with micro- or sub-micromolar activities at both targets and excellent selectivity over hCB1 and AChE, respectively. Computational studies of the first- and second-generation lead structures by applying molecular dynamics (MD) on the active hCB2 R model, along with docking and MD on hBChE, has enabled an explanation of their binding profiles at the protein levels and opened the way for further optimization. Dual acting compounds with "balanced" affinities and excellent selectivities could be obtained that represent leads for treatment of both cognitive and pathophysiological impairment occurring in neurodegenerative disorders. PMID- 26548366 TI - Effects of physical training on age-related balance and postural control. AB - In this paper, we review the effects of physical activity on balance performance in the elderly. The increase in the incidence of falls with age reflects the disorders of balance-related to aging. We are particularly interested in age related changes in the balance control system as reflected in different static and dynamic balance tests. We report the results of studies demonstrating the beneficial effects of physical activity on postural balance. By comparing groups of practitioners of different physical activities, it appears that these effects on postural control depend on the type of activity and the time of practice. Thus, we have focused in the present review on "proprioceptive" and "strength" activities. Training programs offering a combination of several activities have demonstrated beneficial effects on the incidence of falls, and we present and compare the effects of these two types of training activities. It emerges that there are differential effects of programs of activities: while all activities improve participants' confidence in their ability, the "proprioceptive" activities rather improve performance in static tasks, while "strength" activities tend to improve performance in dynamic tasks. These effects depend on the targeted population and will have a greater impact on the frailest subjects. The use of new technologies in the form of "exergames" may also be proposed in home-based exercises. PMID- 26548367 TI - Mycophenolic acid inhibits the phosphorylation of nuclear factor-kappaB and Akt in renal tubular epithelial cells. AB - Renal tubulointerstitial injury induced by albumin overload is a critical stage during the progression of renal interstitial fibrosis and progression of chronic renal diseases. Inosine-5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF), a pro-drug of mycophenolic acid (MPA), is known to attenuate the progression of renal interstitial fibrosis; however, the underlying molecular mechanisms of the anti-fibrotic effects of derivatives of MMF have not yet been studied. The present study assessed the effects of the MPA on renal tubular epithelial cells. Transforming growth factor beta 1 (TGF-beta1) has been indicated to have a central role in the underlying molecular mechanisms of renal fibrosis; furthermore, nuclear transcription factor-kappaB (NF-kappaB) is a transcription factor associated with the production of inflammatory cytokines, cell proliferation and apoptosis. In addition, the Akt signaling pathway has important roles in cell proliferation, differentiation, metabolism and apoptosis. The present study subjected the NRK52E rat kidney epithelial-derived cell line to albumin overload, which resulted in an increase in TGF-beta1 production as well as phosphorylation of Akt and the binding activity of NF-kappaB to the promoter region of the TGF-beta1 gene, which was, however, reduced following pre incubation of the cells with MPA. In addition, the effects of albumin were partially blocked by Ly294002, a specific inhibitor of Akt. In conclusion, the results of the present study suggested that MPA may exert its anti-fibrotic effects by inhibiting the upregulation of TGF-beta1 and the activation of NF kappaB following albumin overload, which may be partly dependent on the Akt pathway. PMID- 26548368 TI - DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis. AB - OBJECTIVES AND BACKGROUND: The involvement of DNA methylation in periodontal disease is not clear. Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis is involved in the progression of periodontal disease. We recently developed an in vitro model of LPS infection in human periodontal fibroblast cells (HPdLFs) for a prolonged period. In this study, we examined genome-wide analysis of DNA methylation in HPdLFs stimulated with LPS derived from P. gingivalis for a prolonged period. We noted the hypermethylation of extracellular matrix (ECM)-related genes and examined whether hypermethylation affected their transcription levels. MATERIAL AND METHODS: HPdLFs were grown in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. The culture was repeated, alternating 3 d with LPS derived from P. gingivalis and 3 d without LPS for 1 mo. Untreated samples were used as controls. DNA was analyzed using the human CpG island microarray. Quantitative methylation-specific polymerase chain reaction was carried out to confirm reproducibility of the microarray data. The expression levels of mRNA of the selected ECM-related genes from the data were analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found 25 ECM-related genes with hypermethylation at the CpG island of the promoter region, which exhibited a fourfold greater hypermethylation than controls. Among these genes, hypermethylation of nine ECM-related genes, FANK1, COL4A1-A2, 12A1 and 15A1, LAMA5 and B1, MMP25, POMT1 and EMILIN3, induced a significantly downregulated expression of their mRNA. CONCLUSION: These results indicate that LPS derived from P. gingivalis may cause DNA hypermethylation of some ECM-related genes followed by downregulated expression of their transcriptional levels. PMID- 26548369 TI - Synthesis of bi-phase dispersible core-shell FeAu@ZnO magneto-opto-fluorescent nanoparticles. AB - Bi-phase dispersible core-shell FeAu@ZnO magneto-opto-fluorescent nanoparticles were synthesized by a modified nanoemulsion process using poly(ethylene glycol) block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO) as the surfactant. The morphology and crystal structure of the nanoparticles were studied by TEM/HRTEM and XRD. The nanoparticles manifest soft ferromagnetic and/or near superparamagnetic behavior with a small coercivity of ~19 Oe at room temperature. The corresponding magnetic hysteresis curves were elucidated by the modified Langevin equation. The FTIR study confirms the PEO-PPO-PEO molecules on the surface of the nanoparticles. The UV-vis and PL results reveal the well behaved absorption bands including surface plasmon resonance and multiple visible fingerprint photoluminescent emissions of the nanoparticles dispersed in both hydrophilic and hydrophobic solvents. Moreover, the processes of solvent dispersion-collection of the nanoparticles were demonstrated for application readiness of such core-shell nanostructures. PMID- 26548371 TI - Staphylococcus aureus bacteraemia associated with injected new psychoactive substances. AB - Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has been a recent increase in the use of injected new psychoactive substances (NPS). Patients who have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-threatening complications. We describe a unique case-series of 14 episodes of SAB in ten patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating pulmonary lesions (P < 0.05) compared to those who inject only opiates. Cases of SAB in people who inject NPS have contributed to a significant rise in the overall incidence of SAB in people who inject drugs (P < 0.05) which has in turn impacted on the ability of Lothian to meet national targets for reducing the incidence of SAB. PMID- 26548370 TI - Par-4 secretion: stoichiometry of 3-arylquinoline binding to vimentin. AB - Advanced prostate tumors usually metastasize to the lung, bone, and other vital tissues and are resistant to conventional therapy. Prostate apoptosis response-4 protein (Par-4) is a tumor suppressor that causes apoptosis in therapy-resistant prostate cancer cells by binding specifically to a receptor, Glucose-regulated protein-78 (GRP78), found only on the surface of cancer cells. 3-Arylquinolines or "arylquins" induce normal cells to release Par-4 from the intermediate filament protein, vimentin and promote Par-4 secretion that targets cancer cells in a paracrine manner. A structure-activity study identified arylquins that promote Par-4 secretion, and an evaluation of arylquin binding to the hERG potassium ion channel using a [(3)H]-dofetilide binding assay permitted the identification of structural features that separated this undesired activity from the desired Par-4 secretory activity. A binding study that relied on the natural fluorescence of arylquins and that used the purified rod domain of vimentin (residues 99-411) suggested that the mechanism behind Par-4 release involved arylquin binding to multiple sites in the rod domain. PMID- 26548372 TI - Atomistic Free Energy Model for Nucleic Acids: Simulations of Single-Stranded DNA and the Entropy Landscape of RNA Stem-Loop Structures. AB - While single-stranded (ss) segments of DNAs and RNAs are ubiquitous in biology, details about their structures have only recently begun to emerge. To study ssDNA and RNAs, we have developed a new Monte Carlo (MC) simulation using a free energy model for nucleic acids that has the atomisitic accuracy to capture fine molecular details of the sugar-phosphate backbone. Formulated on the basis of a first-principle calculation of the conformational entropy of the nucleic acid chain, this free energy model correctly reproduced both the long and short length scale structural properties of ssDNA and RNAs in a rigorous comparison against recent data from fluorescence resonance energy transfer, small-angle X-ray scattering, force spectroscopy and fluorescence correlation transport measurements on sequences up to ~100 nucleotides long. With this new MC algorithm, we conducted a comprehensive investigation of the entropy landscape of small RNA stem-loop structures. From a simulated ensemble of ~10(6) equilibrium conformations, the entropy for the initiation of different size RNA hairpin loops was computed and compared against thermodynamic measurements. Starting from seeded hairpin loops, constrained MC simulations were then used to estimate the entropic costs associated with propagation of the stem. The numerical results provide new direct molecular insights into thermodynaimc measurement from macroscopic calorimetry and melting experiments. PMID- 26548373 TI - Post-Translational Regulation of FLOWERING LOCUS T Protein in Arabidopsis. PMID- 26548374 TI - Time-dependent simulation and analytical modelling of electronic Mach-Zehnder interferometry with edge-states wave packets. AB - We compute the exact single-particle time-resolved dynamics of electronic Mach Zehnder interferometers based on Landau edge-states transport, and assess the effect of the spatial localization of carriers on the interference pattern. The exact carrier dynamics is obtained by solving numerically the time-dependent Schrodinger equation with a suitable 2D potential profile reproducing the interferometer design. An external magnetic field, driving the system to the quantum Hall regime with filling factor one, is included. The injected carriers are represented by a superposition of edge states, and their interference pattern controlled via magnetic field and/or area variation-reproduces the one of (Ji et al 2003 Nature 422 415). By tuning the system towards different regimes, we find two additional features in the transmission spectra, both related to carrier localization, namely a damping of the Aharonov-Bohm oscillations with increasing difference in the arms length, and an increased mean transmission that we trace to the energy-dependent transmittance of quantum point contacts. Finally, we present an analytical model, also accounting for the finite spatial dispersion of the carriers, able to reproduce the above effects. PMID- 26548375 TI - A comparative approach to assess drivers of success in mammalian conservation recovery programs. AB - The outcomes of species recovery programs have been mixed; high-profile population recoveries contrast with species-level extinctions. Each conservation intervention has its own challenges, but to inform more effective management it is imperative to assess whether correlates of wider recovery program success or failure can be identified. To contribute to evidence-based improvement of future conservation strategies, we conducted a global quantitative analysis of 48 mammalian recovery programs. We reviewed available scientific literature and conducted semistructured interviews with conservation professionals involved in different recovery programs to investigate ecological, management, and political factors associated with population recoveries or declines. Identifying and removing threats was significantly associated with increasing population trend and decreasing conservation dependence, emphasizing that populations are likely to continue to be compromised in the absence of effective threat mitigation and supporting the need for threat monitoring and adaptive management in response to new and potential threats. Lack of habitat and small population size were cited as limiting factors in 56% and 42% of recovery programs, respectively, and both were statistically associated with increased longer term dependence on conservation intervention, demonstrating the importance of increasing population numbers quickly and restoring and protecting habitat. Poor stakeholder coordination and management were also regularly cited by respondents as key weaknesses in recovery programs, indicating the importance of effective leadership and shared goals and management plans. Project outcomes were not influenced by biological or ecological variables such as body mass or habitat, which suggests that these insights into correlates of conservation success and failure are likely to be generalizable across mammals. PMID- 26548376 TI - gamma-Fe2O3 Nanocrystalline Microspheres with Hybrid Behavior of Battery Supercapacitor for Superior Lithium Storage. AB - Maghemite (gamma-Fe2O3) nanocrystalline microspheres (MNMs) self-assembled with 52 nm nanocrystals bridged with FeOOH around grain boundaries were formed by solvothermal reaction and thermal oxidation. The unique architecture endows the MNMs with the lithium storage behavior of a hybrid battery-supercapacitor electrode: initial charge capacity of 1060 mAh g(-1) at the 100 mA g(-1) rate, stable cyclic capacity of 1077.9 mAh g(-1) at the same rate after 140 cycles, and rate capability of 538.8 mAh g(-1) at 2400 mA g(-1). This outstanding performance was attributed to the nanocrystal superiority, which shortens the Li(+) diffusion paths. The mechanism of this hybrid anode material was investigated with experimental measurements and structural analysis. The results indicate that at the first discharge, the MNM nanocrystal microsphere, whose structure can buffer the volume change that occurs during lithiation/delithiation, goes through four stages: Li(+) insertion in cation vacancies, spinel-to-rocksalt transformation, Li(+) intercalation of Li(1.75+x)Fe2O3 nanocrystals, and interfacial Li storage around nanocrystal boundaries. Only the latter two stages were reversible at and after the second charging/discharging cycle, exhibiting the hybrid behavior of a battery-supercapacitor with superior lithium storage. PMID- 26548377 TI - Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study. AB - In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes. PMID- 26548378 TI - Glutathione S-Transferase M1 and T1 Gene Polymorphisms and the Outcome of Chronic Hepatitis C Virus Infection in Egyptian Patients. AB - We analysed the distribution of GSTM1 and GSTT1 gene polymorphisms in Egyptian patients with chronic hepatitis C, and investigated their relationship to the clinical outcome of chronic hepatitis C virus (HCV) infection. This study included 169 patients with chronic HCV infection and 145 healthy and matched controls.GSTM1 and GSTT1 polymorphisms were genotyped by multiplex polymerase chain reaction. Individual GSTM1 null and GSTT1 null genotypes were more frequent in patients versus control subjects [OR, 4 (95% CI, 2.5-6.4); P ? 0.001] and [OR, 1.7 (95% CI, 1.1-2.6); P = 0.025], respectively. The patient group showed a higher frequency of the combined GSTM1/GSTT1 double-null genotype than the control group [OR, 1.8 (95% CI, 1.1-2.9); P = 0.016]. The distribution frequencies of the combined GSTM1/GSTT1 double-null genotype were significantly different [OR, 0.5 (95% CI, 0.25-0.99); P = 0.049] between F0-F3 and F4. There were no significant differences between the two groups with regard to other genotypes. The combined GSTM1/GSTT1 double-null genotype was significantly increased in Child-Pugh C patients in comparison to Child-Pugh A+B (P = 0.02). There was no significant difference between different classes with regard to other genotypes. In conclusion, we identified an association between the combined GSTM1/GSTT1 double-null genotype and advanced liver fibrosis and outcome of chronic HCV infection in Egyptian patients. PMID- 26548379 TI - The prevalence of type 2 diabetes among older people in Africa: a systematic review. AB - Little information is available on the prevalence of diabetes in people aged 55 years or older living on the African continent. We did a systematic review of the prevalence of type 2 diabetes in studies reported from Jan 1, 2000, to June 30, 2015, to provide accurate data for monitoring future trends. We did a comprehensive literature search using an African search filter and extracted and synthesised data from full papers. Among 1473 identified citations, 41 studies providing 49 separate data contributions involving 16 086 individuals met the inclusion criteria. The overall prevalence of diabetes was 13.7% (95% CI 11.3 16.3) and was higher in studies based on the oral glucose tolerance test (23.9%, 17.7-30.7, 12 contributions with 3415 participants) than fasting blood glucose criteria (10.9%, 8.9-13.0, 37 contributions with 12 671 participants; p<0.001). Prevalence was also higher in non-STEPS than in STEPS studies (17.1%, 95% CI 13.6 20.9) vs 9.6%, 6.6-13.0, p=0.003) and in urban than in rural settings (19.7%, 15.0-24.9 vs 7.9%, 4.6-12.0, p=0.0002), but did not differ significantly across age groups, sex, sample size, year of publication, region, or population coverage. These data highlight the need to reduce diabetes risk factors and implement adequate management strategies. In addition, they suggest that uniform diagnostic methods should be used across African countries and elsewhere to enable assessment of trends in diabetes prevalence and the success of diabetes prevention strategies. A collaborative initiative is required between key international and national diabetes and geriatric organisations to improve diabetes care for the older population in Africa and worldwide. PMID- 26548380 TI - Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials. AB - OBJECTIVE: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. METHODS: Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. RESULTS: In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. CONCLUSION: Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study. PMID- 26548381 TI - Supramolecular Assembly of Poly(propyleneimine) Dendrimers Driven By Simple Monovalent Counterions. AB - The self-assembly of semiglobular, positively charged poly(propyleneimine) (PPI) dendrimers with small monovalent counterions (e.g., Cl(-)) in water/acetone mixtures was investigated. We showed that PPI dendrimers can assemble into hollow, spherical, single-layered blackberry-type structures mediated by the presence of monovalent counterions. The effects on the assembly of changing the solvent polarity and adjusting the pH were further investigated to confirm the presence of electrostatic interactions and hydrogen bonding as the driving forces. Results showed that PPI dendrimers form stable, hollow spheres in 5-20% v/v acetone/water and that the size of the spheres decreases monotonically as the solvent polarity and/or the charge on the dendrimers (i.e., lower solution pH) increases. This is the first example to show that small monovalent counterions can trigger attraction among PPI dendrimers (or broadly defined polyelectrolytes) that is strong enough to bring them together to form large, stable supramolecular assemblies, which indicates that these organic macroions have similar solution behavior to more-well-defined inorganic molecular macroions. PMID- 26548382 TI - [Nurses are essential to care for refugees]. PMID- 26548383 TI - [Patient's desire to live needs to be taken into account]. PMID- 26548384 TI - [Depression and its non-drug treatments]. AB - The history of depression has evolved over the centuries as have its treatments, and we are now witnessing the emergence of non-drug treatments. The need for the continuous improvement of knowledge and care practices in the area of mood disorders is one of the key issues. PMID- 26548385 TI - [Non-drug therapies, working on emotions]. AB - Cognitive behavioural therapies are indicated for people in mental pain and also recommended in the treatment of a variety of psychological disorders. The aim is to replace the inappropriate behaviour by more adapted behaviour. Positive psychology is interested not so much in mental health disorders as in well-being and happiness. A variety of therapeutic trends which the caregiver can use to help and support patients in regaining their bearings. PMID- 26548386 TI - [Treating depression through mindfulness-based cognitive therapy]. AB - Mindfulness is the art of being fully present in what we are doing, without judgement and without expectation. A therapeutic education programme was created in the 1990s in order to combat depression and generalised anxiety disorder. In France, this programme will be used in psychiatry. Meditation and psychoeducation will enable patients with depression to gradually establish a detachment with regard to the psychological and emotional content. PMID- 26548387 TI - [Energy and emotion in mental health through martial arts]. AB - A patient's arrival in a mental health unit corresponds to a profound malaise in their life. Admission to hospital leads the patient to be cut off from their environment but is also the opportunity for thinking and reconstruction. A workshop based on martial arts enables patients to rediscover their body, verbalise their suffering and regain self-confidence. PMID- 26548388 TI - [Transcranial magnetic stimulation used in psychiatry]. AB - Repetitive transcranial magnetic stimulation is a non-invasive treatment technique, using electromagnetism properties. It has been used for around twenty years in neurology (treatment of neuropathic pain, certain abnormal movements, Parkinson's disease), and in psychiatry (obsessive compulsive disorder, hallucinations, mood disorders, etc.). The presence and support of a nurse during the sessions is essential. PMID- 26548389 TI - [Ethical questioning at the heart of clinical reflection]. AB - Ethical questioning within a team contributes to the personalisation of care. This approach has had a strong presence in the career of Sebastien Kibler, a nurse manager, and forms the basis for his day-to-day clinical thinking. PMID- 26548390 TI - [My Hospi Friends, a social network for patients]. AB - Making the hospital stay as agreeable as possible by fighting against patients' isolation and loneliness is not easy. In order to make the hospital more hospitable, Foch Hospital in Suresnes has chosen to focus on patient well-being. The initiative of a young entrepreneur has helped to support the hospital in this approach. PMID- 26548391 TI - [Guinea: the army nurses caring for health workers infected with Ebola]. AB - In the first half of 2015, army nurses from the French Army, worked with the Conakry health worker treatment centre in Guinea. Their aim was to save the lives of health workers risking their lives in the fight against the Ebola epidemic. This article describes a mission which proved memorable both on a human and professional level. PMID- 26548392 TI - [Bariatric surgery and patient therapeutic education]. AB - Weight loss surgery or "bariatric surgery", used in cases of severe obesity, is a complex procedure aiming to reduce food intake. An increasingly accessible technique, it requires a long postoperative follow-up and a change in eating habits. Patient therapeutic education encourages the patient to become a player in their care. PMID- 26548393 TI - [Non-invasive ventilation and acute cardiogenic pulmonary oedema]. AB - Non-invasive ventilation is an integral part of therapies used in patients presenting acute cardiogenic pulmonary oedema. In cardiac intensive care, these patients are treated by teams trained and practised in this technique. The nurses play a central role in the support and monitoring of the patients. PMID- 26548394 TI - [Blood glucose monitoring: teach the patient good practices]. PMID- 26548395 TI - Giving a Newborn a Bath in her Parents' Presence. AB - Today, Sophie is working on the maternity ward. She is going to give Manon, David and Laura's first born, a bath. Manon was born on the day before. She weighs 3.350kg and is 49cm long. She has already got a lot of fuzzy brown hair. Both parents are looking forward to watching and learning how to care for their new baby. PMID- 26548396 TI - [Explore the doctor-patient relationship through a 'voice' workshop]. PMID- 26548397 TI - [The nurse and a wound management]. PMID- 26548398 TI - [The nurse and the diagnosis of fungal infections of the respiratory system]. PMID- 26548399 TI - Influence of an Inorganic Interlayer on Exciton Separation in Hybrid Solar Cells. AB - It has been shown that in hybrid polymer-inorganic photovoltaic devices not all the photogenerated excitons dissociate at the interface immediately, but can instead exist temporarily as bound charge pairs (BCPs). Many of these BCPs do not contribute to the photocurrent, as their long lifetime as a bound species promotes various charge carrier recombination channels. Fast and efficient dissociation of BCPs is therefore considered a key challenge in improving the performance of polymer-inorganic cells. Here we investigate the influence of an inorganic energy cascading Nb2O5 interlayer on the charge carrier recombination channels in poly(3-hexylthiophene-2,5-diyl) (P3HT)-TiO2 and PbSe colloidal quantum dot-TiO2 photovoltaic devices. We demonstrate that the additional Nb2O5 film leads to a suppression of BCP formation at the heterojunction of the P3HT cells and also a reduction in the nongeminate recombination mechanisms in both types of cells. Furthermore, we provide evidence that the reduction in nongeminate recombination in the P3HT-TiO2 devices is due in part to the passivation of deep midgap trap states in the TiO2, which prevents trap-assisted Shockley-Read-Hall recombination. Consequently a significant increase in both the open-circuit voltage and the short-circuit current was achieved, in particular for P3HT-based solar cells, where the power conversion efficiency increased by 39%. PMID- 26548400 TI - Predicting 30-day Hospital Readmission with Publicly Available Administrative Database. A Conditional Logistic Regression Modeling Approach. AB - INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". BACKGROUND: Hospital readmissions raise healthcare costs and cause significant distress to providers and patients. It is, therefore, of great interest to healthcare organizations to predict what patients are at risk to be readmitted to their hospitals. However, current logistic regression based risk prediction models have limited prediction power when applied to hospital administrative data. Meanwhile, although decision trees and random forests have been applied, they tend to be too complex to understand among the hospital practitioners. OBJECTIVES: Explore the use of conditional logistic regression to increase the prediction accuracy. METHODS: We analyzed an HCUP statewide inpatient discharge record dataset, which includes patient demographics, clinical and care utilization data from California. We extracted records of heart failure Medicare beneficiaries who had inpatient experience during an 11-month period. We corrected the data imbalance issue with under-sampling. In our study, we first applied standard logistic regression and decision tree to obtain influential variables and derive practically meaning decision rules. We then stratified the original data set accordingly and applied logistic regression on each data stratum. We further explored the effect of interacting variables in the logistic regression modeling. We conducted cross validation to assess the overall prediction performance of conditional logistic regression (CLR) and compared it with standard classification models. RESULTS: The developed CLR models outperformed several standard classification models (e.g., straightforward logistic regression, stepwise logistic regression, random forest, support vector machine). For example, the best CLR model improved the classification accuracy by nearly 20% over the straightforward logistic regression model. Furthermore, the developed CLR models tend to achieve better sensitivity of more than 10% over the standard classification models, which can be translated to correct labeling of additional 400 - 500 readmissions for heart failure patients in the state of California over a year. Lastly, several key predictor identified from the HCUP data include the disposition location from discharge, the number of chronic conditions, and the number of acute procedures. CONCLUSIONS: It would be beneficial to apply simple decision rules obtained from the decision tree in an ad-hoc manner to guide the cohort stratification. It could be potentially beneficial to explore the effect of pairwise interactions between influential predictors when building the logistic regression models for different data strata. Judicious use of the ad-hoc CLR models developed offers insights into future development of prediction models for hospital readmissions, which can lead to better intuition in identifying high-risk patients and developing effective post-discharge care strategies. Lastly, this paper is expected to raise the awareness of collecting data on additional markers and developing necessary database infrastructure for larger-scale exploratory studies on readmission risk prediction. PMID- 26548401 TI - IL-8, a novel messenger to cross-link inflammation and tumor EMT via autocrine and paracrine pathways (Review). AB - The epithelial-mesenchymal transition (EMT) is a process through which epithelial cells trans-differentiate and acquire an aggressive mesenchymal phenotype. In tumor cells, EMT is a vital step of tumor progression and metastasis. Amid the increasing interest in tumor EMT, only a few studies focused on the soluble mediators secreted by tumor cells passing through this phenotypic switch. In this review, we focus on the essential role of interleukin-8 (IL-8) signaling for the acquisition and maintenance of tumor EMT via direct and indirect mechanisms. Besides the autocrine loop between IL-8 and tumor cells that have gone through EMT, IL-8 could potentiate adjacent epithelial tumor cells into a mesenchymal phenotype via a paracrine mode. Moreover, understanding the role of IL-8 in EMT will provide insight into the pathogenesis of tumor progression and may facilitate the development of an effective strategy for the prevention and treatment of metastatic cancer. PMID- 26548402 TI - Low bandgap semiconducting polymers for polymeric photovoltaics. AB - In order to develop high performance polymer solar cells (PSCs), full exploitation of the sun-irradiation from ultraviolet (UV) to near infrared (NIR) is one of the key factors to ensure high photocurrents and thus high efficiency. In this review, five of the effective design rules for approaching LBG semiconducting polymers with high molar absorptivity, suitable energy levels, high charge carrier mobility and high solubility in organic solvents are overviewed. These design stratagems include fused heterocycles for facilitating pi-electron flowing along the polymer backbone, groups/atoms bridging adjacent rings for maintaining a high planarity, introduction of electron-withdrawing units for lowering the bandgap (Eg), donor-acceptor (D-A) copolymerization for narrowing Eg and 2-dimensional conjugation for broadened absorption and enhanced hole mobility. It has been demonstrated that LBG semiconducting polymers based on electron-donor units combined with strong electron-withdrawing units possess excellent electronic and optic properties, emerging as excellent candidates for efficient PSCs. While for ultrasensitive photodetectors (PDs), which have intensive applications in both scientific and industrial sectors, sensing from the UV to the NIR region is of critical importance. For polymer PDs, Eg as low as 0.8 eV has been obtained through a rational design stratagem, covering a broad wavelength range from the UV to the NIR region (1450 nm). However, the response time of the polymer PDs are severely limited by the hole mobility of LBG semiconducting polymers, which is significantly lower than those of the inorganic materials. Thus, further advancing the hole mobility of LBG semiconducting polymers is of equal importance as broadening the spectral response for approaching uncooled ultrasensitive broadband polymer PDs in the future study. PMID- 26548403 TI - Cerebral asymmetry for language: Comparing production with comprehension. AB - Although left-hemispheric damage can impair both the production and comprehension of language, it has been claimed that comprehension is more bilaterally represented than is production. A variant of this theme is based on the theory that different aspects of language are processed by a dorsal stream, responsible for mapping words to articulation, and a ventral stream for processing input for meaning. Some have claimed that the dorsal stream is left-hemispheric, while the ventral stream is bilaterally organized. We used fMRI to record activation while left- and right-handed participants performed covert word-generation task and judged whether word pairs were synonyms. Regions of interest were Broca's area as part of the dorsal stream and the superior and middle temporal gyri as part of the ventral stream. Laterality indices showed equal left-hemispheric lateralization in Broca's area for word generation and both Broca's area and temporal lobe for the synonym judgments. Handedness influenced laterality equally in each area and task, with right-handers showing stronger left-hemispheric dominance than left-handers. Although our findings provide no evidence that asymmetry is more pronounced for production than for comprehension, correlations between the tasks and regions of interest support the view that lateralization in the temporal lobe depends on feedback influences from frontal regions. PMID- 26548405 TI - Effect of Nutritional Intervention on Food Choices of French Students in Middle School Cafeterias, Using an Interactive Educational Software Program (Nutri Advice). AB - OBJECTIVE: To evaluate the impact of interactive Nutri-Advice kiosks on children's nutritional skills and their ability to apply it to food choices in a middle school cafeteria menu (food choice competencies). DESIGN: Quasi experimental design; pre/post-test. SETTING: Freestanding interactive computer terminals (kiosks) were installed in three middle schools in Toulouse, France. PARTICIPANTS: A total of 580 children were enrolled into the study (mean age, 13 +/- 1 years). INTERVENTION: Each child's physiological profile was stored in a personal barcode card. During 1 school year, once a day, each child could access the kiosk with this card, trying to find the most balanced meal according to his or her profile and the food available on the cafeteria menu. MAIN OUTCOME MEASURES: Children's food choice competency changes and body mass index z-score were evaluated. ANALYSIS: Significance of change in food choice competencies (postintervention vs baseline) was examined using paired t test. RESULTS: Across the study, children chose significantly less cheese and pastry or desserts, and significantly more starchy food and dairy, and tended to choose fruits and vegetables more often. Body mass index z-score decreased significantly during the period. CONCLUSIONS AND IMPLICATIONS: Personalized nutrition counseling through an interactive device has the potential to improve the food choice competencies of children. PMID- 26548404 TI - Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH adapted killifish. AB - Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 MUg/L and 50.4 MUg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in killifish, and that locomotor alterations could be observed in early larval stages. Additionally, our study highlights the resistance to behavioral alterations caused by low-level PAH mixture exposure in the adapted killifish population. Furthermore, this is the first longitudinal behavioral study to use killifish, an environmentally important estuarine teleost fish, and this testing framework can be used for future contaminant assessment. PMID- 26548406 TI - A novel aptasensor for thrombin detection based on alkaline phosphatase decorated ZnO/Pt nanoflowers as signal amplifiers. AB - To remedy the problems caused by the introduction of an additional electron mediator and realize signal amplification, a new strategy has been presented to construct an electrochemical aptasensor for thrombin detection based on the cascade electrocatalysis of alkaline phosphatase (ALP) and Pt nanoparticle (PtNP) functionalized ZnO nanoflowers. PMID- 26548407 TI - Intracellular host-guest assembly of gold nanoparticles triggered by glutathione. AB - A simple method to achieve host-guest assembly of gold nanoparticles triggered by intracellular glutathione was demonstrated. The increased size of nanoparticles not only enhanced their retention time within cancer cells, but also induced apoptosis. This strategy may open an avenue for the development of smart nanocarriers for intracellular diagnosis and therapy. PMID- 26548408 TI - Translational Research: Linking Research With Practice: Evidence to Improve the Health of Children. PMID- 26548409 TI - Irritable bowel syndrome is associated not only with organic but also psychogenic erectile dysfunction. AB - This study investigated the correlation between irritable bowel syndrome (IBS) and organic erectile dysfunction (OED) and psychogenic erectile dysfunction (PED), and analyzed the influence of various comorbidities. Data were obtained from reimbursement claims of the National Health Insurance Program in Taiwan. We selected male patients aged >20 years, who were diagnosed with IBS during the 2000-2011 period as the IBS cohort. The index date for patients with IBS was the date of their first medical visit. We excluded patients with a diagnosis of OED and PED at baseline and those without information on age and sex. The IBS to non IBS cohorts were estimated using univariable and multivariable Cox proportional hazards regression model. Adjusted hazard ratios were determined after adjusting for age and comorbidities. The Kaplan-Meier method was used to plot the cumulative incidence of OED and PED, and a log-rank test was used to compare the cohorts. A total of 15,533 IBS patients and 62,124 controls without IBS were enrolled in our study. Among the study participants, 48.2% were 49 years of age or younger. Patients with IBS were more likely to develop erectile dysfunction (ED) than those without IBS. Patients with IBS were 2.12 times more likely to develop OED and 2.38 times more likely to develop PED than the controls. There is an increased risk of both PED and OED in patients with IBS. Not only with organic but also PED should be considered when patients with IBS complain of ED. PMID- 26548410 TI - Platelet indices in vasculogenic erectile dysfunction. PMID- 26548411 TI - Exploring the mechanism of how tvMyb2 recognizes and binds ap65-1 by molecular dynamics simulations and free energy calculations. AB - TvMyb2, one of the Myb-like transcriptional factors in Trichomonas vaginalis, binds to two closely spaced promoter sites, MRE-1/MRE-2r and MRE-2f, on the ap65 1 gene. However, detailed dynamical structural characteristics of the tvMyb2-ap65 1 complex and a detailed study of the protein in the complex have not been done. Focused on a specific tvMyb2-MRE-2-13 complex (PDB code: ) and a series of mutants K51A, R84A and R87A, we applied molecular dynamics (MD) simulation and molecular mechanics generalized Born surface area (MM-GBSA) free energy calculations to examine the role of the tvMyb2 protein in recognition interaction. The simulation results indicate that tvMyb2 becomes stable when it binds the DNA duplex. A series of mutants, K51A, R84A and R87A, have been followed, and the results of statistical analyses of the H-bond and hydrophobic contacts show that some residues have significant influence on recognition and binding to ap65-1 DNA. Our work gives important information to understand the interactions of tvMyb2 with ap65-1. PMID- 26548412 TI - Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain. AB - During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; p<0.001) of aged rats compared to young rats, however no significant differences were detected in synaptic levels in the PFC region. Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. PMID- 26548413 TI - Metabotropic glutamate 5 receptor in the infralimbic cortex contributes to descending pain facilitation in healthy and arthritic animals. AB - The involvement of the prefrontal cortex in pain processing has been recently addressed. We studied the role of the infralimbic cortex (IL) and group I metabotropic glutamate receptors (mGluRs) in descending modulation of nociception in control and monoarthritic (ARTH) conditions. Nociception was assessed using heat-induced paw withdrawal while drugs were microinjected in the IL of rats. Local anesthesia of the IL or the adjacent prelimbic cortex (PL) facilitated nociception, indicating that IL and PL are tonically promoting spinal antinociception. Phasic activation with glutamate (GLU) revealed opposing roles of the PL and IL; GLU in the PL had a fast antinociceptive action, while in the IL it had a slow onset pronociceptive action. IL administration of a local anesthetic or GLU produced identical results in ARTH and control animals. An mGluR5 agonist in the IL induced a pronociceptive effect in both groups, while mGluR5 antagonists had no effect in controls but induced antinociception in ARTH rats. Activation of the IL mGluR1 (through co-administration of mGluR1/5 agonist and mGluR5 antagonist) did not alter nociception in controls but induced antinociception in ARTH animals. IL administration of an mGluR1 antagonist failed to alter nociception in either experimental group. Finally, mGluR5 but not mGluR1 antagonists blocked the pronociceptive action of GLU in both groups. The results indicate that IL contributes to descending modulation of nociception. mGluR5 in the IL enhance nociception in healthy control and monoarthritic animals, an effect that is tonic in ARTH. Moreover, activation of IL mGluR1s attenuates nociception following the development of monoarthritis. PMID- 26548414 TI - Antihyperalgesic effect of tetrodotoxin in rat models of persistent muscle pain. AB - Persistent muscle pain is a common and disabling symptom for which available treatments have limited efficacy. Since tetrodotoxin (TTX) displays a marked antinociceptive effect in models of persistent cutaneous pain, we tested its local antinociceptive effect in rat models of muscle pain induced by inflammation, ergonomic injury and chemotherapy-induced neuropathy. While local injection of TTX (0.03-1 MUg) into the gastrocnemius muscle did not affect the mechanical nociceptive threshold in naive rats, exposure to the inflammogen carrageenan produced a marked muscle mechanical hyperalgesia, which was dose dependently inhibited by TTX. This antihyperalgesic effect was still significant at 24h. TTX also displayed a robust antinociceptive effect on eccentric exercise induced mechanical hyperalgesia in the gastrocnemius muscle, a model of ergonomic pain. Finally, TTX produced a small but significant inhibition of neuropathic muscle pain induced by systemic administration of the cancer chemotherapeutic agent oxaliplatin. These results indicate that TTX-sensitive sodium currents in nociceptors play a central role in diverse states of skeletal muscle nociceptive sensitization, supporting the suggestion that therapeutic interventions based on TTX may prove useful in the treatment of muscle pain. PMID- 26548415 TI - The effects of stress during early postnatal periods on behavior and hippocampal neuroplasticity markers in adult male mice. AB - Infancy is a critical period for brain development. Emerging evidence indicates that stress experienced during that period can have long-term programming effects on the brain and behavior. However, whether different time periods represent different vulnerabilities to the programming of different neurobehavioral domains is not yet known. Disrupted maternal care is known to interfere with neurodevelopmental processes and may lead to the manifestation of behavioral abnormalities in adulthood. Mouse dams confronted with insufficient bedding/nesting material have been shown to provide fragmented maternal care to their offspring. Here, we compared the impact of this model of early-life stress (ELS) during different developmental periods comprising either postnatal days (PNDs) 2-9 (ELS-early) or PND 10-17 (ELS-late) on behavior and hippocampal cell adhesion molecules in male mice in adulthood. ELS-early treatment caused a permanent reduction in bodyweight, whereas this reduction only occurred transiently during juvenility in ELS-late mice. Anxiety was only affected in ELS late mice, while cognition and sociability were equally impaired in both ELS treated groups. We analyzed hippocampal gene expression of the gamma2 subunit of the GABAa receptor (Gabrg2) and of genes encoding cell adhesion molecules. Gabrg2 expression was increased in the ventral hippocampus in ELS-late-treated animals and was correlated with anxiety-like behavior in the open-field (OF) test. ELS early-treated animals exhibited an increase in nectin-1 expression in the dorsal hippocampus, and this increase was associated with the social deficits seen in these animals. Our findings highlight the relevance of developmental age on stress-induced long-term behavioral alterations. They also suggest potential links between early stress-induced alterations in hippocampal Gabrg2 expression and the developmental programming of anxiety and between changes in hippocampal nectin-1 expression and stress-induced social impairments. PMID- 26548416 TI - Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2). AB - The ability of the anti-diabetic drug metformin to inhibit anabolic processes including gluconeogenesis and lipogenesis is partly attributable to activation of the AMP-activated protein kinase (AMPK) pathway. The p160 steroid receptor coactivator 2 (SRC-2) is a key regulator of cellular metabolism and drives expression of the gluconeogenic enzyme glucose-6-phosphatase (G6Pc). Here, we uncovered a role for SRC-2 in the metabolic reprogramming imposed by metformin. In FaO cells, metformin dose-dependently reduced mRNA expression of SRC-2. Microarray analysis of metformin-treated cells revealed an overrepresentation of downregulated genes involved in biosynthesis of lipids and cholesterol. Several metformin-regulated genes including fatty acid synthase (FASN) were validated as transcriptional targets of SRC-2 with promoters characterized by sterol regulatory element (SRE) binding protein (SREBP) recognition sequences. Transactivation assays of the FASN promoter confirmed that SRC-2 is a coactivator of SREBP-1. By suppressing SRC-2 at the transcriptional level, metformin impeded recruitment of SRC-2 and RNA polymerase II to the G6Pc promoter and to SREs of mutual SRC-2/SREBP-1 target gene promoters. Hepatocellular fat accretion was reduced by metformin or knock-down of both SRC-2 and SREBP-1. Accordingly we propose that metformin inhibits glucose and lipid biosynthesis partly by downregulating SRC-2 gene expression. PMID- 26548418 TI - Significance of TGFBR3 allelic loss in the deregulation of TGFbeta signaling in primary human endometrial carcinomas. AB - Downregulation of betaglycan (beta-glycan) [transforming growth factor beta receptor type III (TGFbetaR3)], which belongs to co-receptors of the TGFbeta pathway, occurs in a broad spectrum of primary human malignancies. However, in the case of endometrial cancer (EC), the mechanisms responsible for genetic alterations are still unknown. Therefore, we investigated allelic imbalance at the TGFBR3 locus (1p33-p32) in the context of beta-glycan mRNA and protein expression, as a possible genetic event determining beta-glycan deregulation in EC patients. Study of beta-glycan allelic imbalance in 48 primary human ECs was performed with the use of three different microsatellite markers, spanned within or in direct proximity to the TGFBR3 locus. Real-time PCR and western blotting were used for beta-glycan mRNA and protein quantification methods, respectively. Altogether, 25 of 39 (64%) informative cases and 25 of 48 (52%) of all specimens showed allelic imbalance in at least one microsatellite marker, concomitantly with decrease at both the beta-glycan transcript and protein levels. Interestingly, 54% (15/28), 36% (8/22) and 35% (7/20) of informative ECs displayed allelic loss in D1S188, D1S435 and D1S1588 microsatellite markers, respectively. It is worth pointing out that 5 out of 39 (13%) informative cases showed loss of heterozygosity (LOH) at two microsatellite markers. Microsatellite instability (MSI) was found in two markers, but to a very strictly limited extent. None of the clinicoprognostic features was found to be of significance. Our results suggest that LOH in the TGFBR3 locus may be one of the mechanisms responsible for loss of beta-glycan expression. No correlation of LOH at the TGFBR3 locus with clinicopathological parameters suggests that allelic imbalance may be an early genetic event during neoplastic transformation of human endometrium. PMID- 26548417 TI - Application of dried blood spots to determine vitamin D status in a large nutritional study with unsupervised sampling: the Food4Me project. AB - An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0.001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson's correlation between the measured values and the predicted values was r 0.65, and the sd of their differences was 21.2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study. PMID- 26548420 TI - Retraction: Protective effects of bazedoxifene paired with conjugated estrogens on pancreatic beta-cell dysfunction. AB - This article has been retracted by the Editorial Committee of The Pharmaceutical Society of Japan because it contains scientific misconduct. Although the data published in this article were generated in part by the first author, the authors violated authorship and sponsorship protocol. PMID- 26548419 TI - Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats. AB - Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)-induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma-specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high-risk patients, including chronic hepatitis and cirrhosis. PMID- 26548421 TI - Sexual Excitation/Sexual Inhibition Inventory (SESII-W/M): Adaptation and Validation Within a Portuguese Sample of Men and Women. AB - The SESII-W/M is a self-report measure assessing factors that inhibit and enhance sexual arousal in men and women. The goal of this study was to adapt and validate it in a sample of Portuguese men and women. A total of 1,723 heterosexual men and women participated through a web survey, with ages ranging from 18 to 72 years old (M = 36.05, SD = 11.93). The levels of internal consistency were considered satisfactory in the first four factors, but not in Setting and Dyadic Elements of the Sexual Interaction. Confirmatory factor analysis partially supported the six factor, 30-item model, as factor loadings and squared multiple correlations pointed to problems with items mainly loading on those two factors. General fit indices were lower than the ones estimated by Milhausen, Graham, Sanders, Yarber, and Maitland (2010). Psychometric sensitivity and construct validity were adequate and gender differences were consistent with the original study. The six factor, 30-item model was retained, but changes to the factors Setting and Dyadic Elements of the Sexual Interaction, and their corresponding items, were recommended in order to strengthen the measure. PMID- 26548422 TI - The importance of postprandial glycemic control: optimizing add-on therapy to basal insulin. AB - Diabetes, mainly type 2 diabetes mellitus (T2DM), is associated with a growing clinical and economic burden in the United States, which is expected to increase in association with an aging population. Sufficient glycemic control in patients with T2DM, in order to reduce the risk of micro- and macrovascular complications associated with diabetes, is mediated by lifestyle modifications and a regimen of increasingly intensive antidiabetes drugs. Several treatments and strategies are available for primary care physicians to select from when choosing the most appropriate therapy for their individual patients with T2DM, but, ultimately, due to the progressive nature of the disease, most of these patients will require insulin therapy to maintain glycemic control. Regimens containing basal and postprandial insulins are widely used, but there is still widespread reluctance to initiate insulin treatment due to fear of weight gain and hypoglycemia. Furthermore, as patients approach recommended glycated hemoglobin targets, postprandial hyperglycemia becomes the main contributor to hyperglycemic exposure, necessitating the timely initiation of prandial treatment. Finally, insulin treatment can be limited by factors like the number of injections, mealtime restrictions, complex titration algorithms and patient adherence. Recent developments in antidiabetes drug research have brought more convenient basal and postprandial regimens closer. Clinical evaluation of the efficacy and safety of basal insulins plus add-on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has yielded promising results. Primary care physicians are continually challenged to optimize insulin treatment strategies to maximize patient outcomes. Emerging strategies such as long-acting basal insulin analogs and short-acting GLP-1 RAs are particularly appealing to address this challenge. PMID- 26548423 TI - Sotagliflozin as a potential treatment for type 2 diabetes mellitus. AB - INTRODUCTION: SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM). AREAS COVERED: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. Original publications in English were selected as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database. EXPERT OPINION: By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secretion, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. While sotagliflozin was first assessed in T2DM, it is now in phase 3 development as an adjuvant treatment in patients with T1DM after positive results from a pilot study. PMID- 26548424 TI - Predictive validation of modeled health technology assessment claims: lessons from NICE. AB - The use of cost-effectiveness modeling to prioritize healthcare spending has become a key foundation of UK government policy. Although the preferred method of evaluation-cost-utility analysis-is not without its critics, it represents a standard approach that can arguably be used to assess relative value for money across a range of disease types and interventions. A key limitation of economic modeling, however, is that its conclusions hinge on the input assumptions, many of which are derived from randomized controlled trials or meta-analyses that cannot be reliably linked to real-world performance of treatments in a broader clinical context. This means that spending decisions are frequently based on artificial constructs that may project costs and benefits that are significantly at odds with those that are achievable in reality. There is a clear agenda to carry out some form of predictive validation for the model claims, in order to assess not only whether the spending decisions made can be justified post hoc, but also to ensure that budgetary expenditure continues to be allocated in the most rational way. To date, however, no timely, effective system to carry out this testing has been implemented, with the consequence that there is little objective evidence as to whether the prioritization decisions made are actually living up to expectations. This article reviews two unfulfilled initiatives that have been carried out in the UK over the past 20 years, each of which had the potential to address this objective, and considers why they failed to deliver the expected outcomes. PMID- 26548425 TI - A red orange extract modulates the vascular response to a recreational dive: a pilot study on the effect of anthocyanins on the physiological consequences of scuba diving. AB - Nutritional antioxidants have been proposed as an expedient strategy to counter the potentially deleterious effects of scuba diving on endothelial function, flow mediated dilation (FMD) and heart function. Sixteen volunteers performing a single standard dive (20 min at 33 m) according to US Navy diving procedures were randomly assigned to two groups: one was administered with two doses of 200 mg of an anthocyanins (AC)-rich extract from red oranges, 12 and 4 h before diving. Anthocyanins supplementation significantly modulated the effects of diving on haematocrit, body water distribution and FMD. AC administration significantly reduces the potentially harmful endothelial effects of a recreational single dive. The lack of any significant effect on the most common markers of plasma antioxidant capacity suggests that the mechanism underlying this protective activity is independent of the putative antioxidant effect of AC and possibly involves cellular signalling modulation of the response to high oxygen. PMID- 26548426 TI - Screening, Brief Intervention, and Referral to Treatment in a rural Ryan White Part C HIV clinic. AB - About 24% of people living with HIV nationally are identified as needing treatment for alcohol or illicit drug use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) has evolved as a strategy to assess and intervene with substance abuse behaviors in various clinical settings. However, less is known about the processes and outcomes of using the SBIRT intervention in outpatient HIV clinics. This paper presents a descriptive analysis of de identified existing SBIRT results data from an outpatient HIV clinic located in western Colorado. From 2008 to 2013, a total of 1616 SBIRT evaluations were done, which included duplicate patients because some individual patients were screened more than once in a given year. Over this time period, 37-49% of encounters per year were notable for tobacco use, 8-21% for alcohol use, 6-16% for marijuana use, 3-9% for amphetamine use, and 0-2% for illicit opioid use. Unique, unduplicated patient data from 2013 revealed 40% of patients used tobacco, 16% used alcohol, and 11% used methamphetamine. Analyses highlighted that the majority of our patient population (58% in 2013) used and/or abused tobacco, alcohol, and/or illicit substances. An alarming finding was the increase in methamphetamine use over time with more than 50-fold prevalence of use in our population compared to national rates. PMID- 26548427 TI - Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug. AB - This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol-gel-sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer-Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium. PMID- 26548428 TI - The Minimum Clinically Important Difference in the Repeatable Battery for the Assessment of Neuropsychological Status. AB - OBJECTIVE: There is no established minimum clinically important difference (MCID) for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) index and total scale scores. This study aimed to estimate the MCID for the RBANS index scores and total scale score. METHOD: Participants included 1,856 ethnic Chinese, older adults. Distribution- and anchor-based methods were used to estimate values for the MCID. Distribution-based estimates were calculated as the standard error of measurement (SEM) and .5 standard deviations (SD). For anchor based estimates, we compared RBANS scores between the clinical dementia rating (CDR) scale no dementia and very mild dementia groups and between the clinical assessment of dementia (CAD) cognitively normal and mild cognitive impairment groups using regression models adjusting for demographic characteristics. RESULTS: Estimates from the CDR anchor were 7.79, 8.63, 10.74, 9.74, 5.61, and 3.77 for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and the attention index, respectively. Estimates from the distribution-based methods were similar to the estimates based on the CDR, except for the language and attention indexes. Estimates from the CAD anchor were larger. CONCLUSIONS: We estimated the MCID for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and attention indexes of the RBANS as 8, 9, 10, 10, 6, and 4 points, respectively. These estimates are best suited to discriminate between patient groups, for example, in a clinical trial setting. Further research is needed using longitudinal data to assess their applicability to assess within patient differences. PMID- 26548430 TI - Endoplasmic reticulum protein 29 is involved in endoplasmic reticulum stress in islet beta cells. AB - Endoplasmic reticulum stress (ERS) is correlated with insulin resistance and islet-cell function. In the present study, the sub-cellular localization and role of ER protein 29 (Erp29) were investigated in an in vitro ERS model of islet beta cells. The INS-1 islet cell line was treated with various concentrations of tunicamycin to establish the ERS model. Immunofluorescence microscopy demonstrated that Erp29 and anti-ER marker protein calnexin were co-localized in NIH3T3 cells, suggesting that Erp29 is localized to the ER. The ERS model induced by tunicamycin showed significantly increased expression of binding immunoglobulin protein (BIP)/glucose-regulated protein 78 (Grp78), which is a marker for ERS, and the expression of Erp29 was also increased at the mRNA and protein levels. Of note, ERS was blocked following small interfering RNA-mediated silencing of Erp29 expression, as indicated by reduced BIP/Grp78 expression. As an ER protein, Erp29 may have an important role in ERS in islet beta cells. PMID- 26548429 TI - Anxiety in youth with autism spectrum disorders: implications for treatment. AB - Anxiety disorders are one of the most common psychiatric comorbidities among children and adolescents with autism spectrum disorders (ASD). There has been a recent proliferation of research examining the prevalence, phenomenology, assessment and treatment of anxiety disorders among youth with ASD. While there is currently very limited support for the use of pharmacological agents to treat anxiety among youth with ASD and comorbid anxiety, there has been overwhelming support across numerous modestly sized controlled studies for the efficacy of cognitive behavioral therapy. This review discusses advances in the treatment literature for anxiety in youth with ASD, and discusses the current evidence base for whether standard treatment needs to be adapted for this population. PMID- 26548431 TI - Peduncular Hallucinosis as First Presentation of Juvenile Pilocytic Astrocytoma. PMID- 26548432 TI - Editorial: Improving Pediatric Cardiac Care in India - Expanding Role of Pediatricians. PMID- 26548433 TI - Ultrastructural Pathology of Oligodendroglial Cells in Traumatic and Hydrocephalic Human Brain Edema: A Review. AB - Oligodendroglial cell changes in human traumatic brain injuries and hydrocephalus have been reviewed and compared with experimental brain edema. Resting unreactive oligodendrocytes, reactive oligodendrocytes, anoxic-ischemic oligodendrocytes, hyperthrophic phagocytic oligodendrocytes, and apoptotic oligodendrocytes are found. Anoxic-ischemic oligodendrocytes exhibit enlargement of endoplasmic reticulum, Golgi complex, and enlargement and disassembly of nuclear envelope. They appear in contact with degenerated myelinated axons. Hypertrophic phagocytic oligodendrocytes engulf degenerated myelinated axons exerting myelinolytic effects. A continuum oncotic and apoptotic cell death type leading to necrosis is observed. The vasogenic and cytotoxic components of brain edema are discussed in relation to oligodendroglial cell changes and reactivity. PMID- 26548434 TI - Lipofuscin Granules in the Epileptic Human Temporal Neocortex with Age. AB - Lipofuscin granules (LGs), the "age pigments", are autofluorescent cell products from lysosomes that diverge in number and size among brain regions. Human temporal cortex from 20- to 55-year-old epileptic subjects were studied with the fat soluble dye Sudan Black, under confocal and electron microscopy. Ultrastructural analysis showed that with age LGs increase in area, but not in number. Proportionally to the LGs area, the electron lucid portion increases and the electron dense reduces over time. The robust increase in lipid components is possibly due to modifications in the neuronal metabolism with age in physiological and pathological conditions. PMID- 26548435 TI - Genistein Treatment Confers Protection against Gliopathy and Vasculopathy of the Diabetic Retina in Rats. AB - Retinopathy remains an important complication of diabetes. This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Fifteen adult male albino rats were divided into two groups; Group I: control (n = 5) and Group II: streptozotocin induced diabetic group (n = 10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina. PMID- 26548436 TI - Three-Dimensional Micro-Computed Tomography Analyses of Induced Periapical Lesions in Transgenic Mice. AB - The aim of this study was to evaluate the three-dimensional (3D) parameters given by the micro-computed tomography (uCT) analysis of experimentally induced periapical lesions in wild type (WT) and knockout mice for the interleukin 22 (IL 22 KO). Periapical lesions were induced in the mandibular first molars of wild type and IL-22 KO mice (n = 12 teeth/group). The animals were euthanized after the experimental periods of 7, 21 and 42 days. The mandibles were removed and exposed to uCT scanning. The analyses were performed by the CTAn software for the tree-dimensional parameters: Tissue Volume (TV), Lesion Volume (LV), Tissue Surface (TS), Lesion Surface (LS), Intersection Surface (IS), and Trabecular Pattern factor (Tb.Pf). After that, the tissue was subjected to routine histologic procedures and to immunohistochemistry analysis. Statistical analysis was performed in the GraphPad software. A t-test was used to compare the differences between the groups with significance level of 5%. The evaluation of the 3D parameters showed statistical significant difference between the groups only at the latest period of periapical lesion development (42 days), for the TV, LV, TS, LS and IS parameters. The immunohistochemistry evaluation confirmed the immunostaining for IL-22 only in the WT mice, surrounding the periapical lesion. There were no differences regarding the trabecular alveolar bone (Tb.Pf) that could influence the lesion development. In conclusion, the 3D parameters showed that the absence of IL-22 leads to detectable differences at 42 days of lesion progression, resulting in smaller periapical lesions. PMID- 26548437 TI - Ultrastructural Changes of the Smooth Muscle in Esophageal Atresia. AB - Esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is a relatively rare congenital anomaly. Despite the advances in the management techniques and neonatal intensive care, esophageal dysmotility remains a very common problem following EA/TEF repair. Our current study aimed to describe the most significant ultrastructural changes of the smooth muscle cells (SMCs) trying to highlight some of the underlying mechanisms of esophageal dysmotility following EA/TEF repair. Twenty-three biopsies were obtained from the tip of the lower esophageal pouch (LEP) of 23 patients during primary repair of EA/TEF. Light microscopic examination was performed with hematoxylin and eosin (HE), and Van Gieson's stains. Ultrastructural examination was done using transmission electron microscopy (TEM). Histopathological examination showed distortion of smooth muscle layer and deposition of an abundant amount of fibrous tissue in between smooth muscles. Using TEM, SMCs exhibited loss of the cell-to-cell adhesion, mitochondrial vacuolation, formation of myelin figures, and apoptotic fragmentation. There were also plasmalemmal projections and formation of ghost bodies. Interestingly, SMCs were found extending pseudopodia-like projections around adjacent collagen fibers. Engulfed collagen fibers by SMCs underwent degradation within autophagic vacuoles. Degeneration of SMCs and deposition of abundant extracellular collagen fibers are prominent pathological changes in LEP of EA/TEF. These changes might contribute to the pathogenesis of esophageal dysmotility in patients who have survived EA/TEF. PMID- 26548439 TI - Anisotropic electronic conduction in stacked two-dimensional titanium carbide. AB - Stacked two-dimensional titanium carbide is an emerging conductive material for electrochemical energy storage which requires an understanding of the intrinsic electronic conduction. Here we report the electronic conduction properties of stacked Ti3C2T2 (T = OH, O, F) with two distinct stacking sequences (Bernal and simple hexagonal). On the basis of first-principles calculations and energy band theory analysis, both stacking sequences give rise to metallic conduction with Ti 3d electrons contributing most to the conduction. The conduction is also significantly anisotropic due to the fact that the effective masses of carriers including electrons and holes are remarkably direction-dependent. Such an anisotropic electronic conduction is evidenced by the I-V curves of an individual Ti3C2T2 particulate, which demonstrates that the in-plane electrical conduction is at least one order of magnitude higher than that vertical to the basal plane. PMID- 26548440 TI - Severe outbreeding and inbreeding depression maintain mating system differentiation in Epipactis (Orchidaceae). AB - In hermaphroditic plants, theory for mating system evolution predicts that populations will evolve to either complete autonomous selfing (AS) or complete outcrossing, depending on the balance between automatic selection favouring self fertilization and costs resulting from inbreeding depression (ID). Theory also predicts that selection for selfing can occur rapidly and is driven by purging of genetic load and the loss of ID. Therefore, selfing species are predicted to have low levels of ID or even to suffer from outbreeding depression (OD), whereas predominantly outcrossing species are expected to have high levels of ID. To test these predictions, we related the capacity of AS to the magnitude of early-acting inbreeding or OD in both allogamous and autogamous species of the orchid genus Epipactis. For each species, the level of AS was assessed under controlled greenhouse conditions, whereas hand-pollinations were performed to quantify early costs of inbreeding or OD acting at the level of fruit and seed production. In the autogamous species, the capacity of AS was high (> 0.72), whereas in the allogamous species AS was virtually absent (< 0.10). Consistent with our hypothesis, allogamous Epipactis species had significantly higher total ID (average: 0.46) than autogamous species, which showed severe costs of OD (average: -0.45). Overall, our findings indicate that strong early-acting ID represents an important mechanism that contributes to allogamy in Epipactis, whereas OD may maintain selfing in species that have evolved to complete selfing. PMID- 26548441 TI - An in situ self-assembly template strategy for the preparation of hierarchical pore metal-organic frameworks. AB - Metal-organic frameworks (MOFs) have recently emerged as a new type of nanoporous materials with tailorable structures and functions. Usually, MOFs have uniform pores smaller than 2 nm in size, limiting their practical applications in some cases. Although a few approaches have been adopted to prepare MOFs with larger pores, it is still challenging to synthesize hierarchical-pore MOFs (H-MOFs) with high structural controllability and good stability. Here we demonstrate a facile and versatile method, an in situ self-assembly template strategy for fabricating stable H-MOFs, in which multi-scale soluble and/or acid-sensitive metal-organic assembly (MOA) fragments form during the reactions between metal ions and organic ligands (to construct MOFs), and act as removable dynamic chemical templates. This general strategy was successfully used to prepare various H-MOFs that show rich porous properties and potential applications, such as in large molecule adsorption. Notably, the mesopore sizes of the H-MOFs can be tuned by varying the amount of templates. PMID- 26548442 TI - Phase boundary of hot dense fluid hydrogen. AB - We investigated the phase transformation of hot dense fluid hydrogen using static high-pressure laser-heating experiments in a laser-heated diamond anvil cell. The results show anomalies in the heating efficiency that are likely to be attributed to the phase transition from a diatomic to monoatomic fluid hydrogen (plasma phase transition) in the pressure range between 82 and 106 GPa. This study imposes tighter constraints on the location of the hydrogen plasma phase transition boundary and suggests higher critical point than that predicted by the theoretical calculations. PMID- 26548443 TI - Two Cases of LQT Syndrome with Malignant Syncope after Switch from Propranolol to Bisoprolol. AB - Propranolol in slow-release form has been the first-line treatment in long QT (LQT) until it was withdrawn from the market. We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5 mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange Nielsen syndrome, previous gangliectomy, and ICD implantation, switched to bisoprolol 5 mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months. PMID- 26548444 TI - Enhanced critical current density in the pressure-induced magnetic state of the high-temperature superconductor FeSe. AB - We investigate the relation of the critical current density (Jc) and the remarkably increased superconducting transition temperature (Tc) for the FeSe single crystals under pressures up to 2.43 GPa, where the Tc is increased by ~8 K/GPa. The critical current density corresponding to the free flux flow is monotonically enhanced by pressure which is due to the increase in Tc, whereas the depinning critical current density at which the vortex starts to move is more influenced by the pressure-induced magnetic state compared to the increase of Tc. Unlike other high-Tc superconductors, FeSe is not magnetic, but superconducting at ambient pressure. Above a critical pressure where magnetic state is induced and coexists with superconductivity, the depinning Jc abruptly increases even though the increase of the zero-resistivity Tc is negligible, directly indicating that the flux pinning property compared to the Tc enhancement is a more crucial factor for an achievement of a large Jc. In addition, the sharp increase in Jc in the coexisting superconducting phase of FeSe demonstrates that vortices can be effectively trapped by the competing antiferromagnetic order, even though its antagonistic nature against superconductivity is well documented. These results provide new guidance toward technological applications of high-temperature superconductors. PMID- 26548445 TI - A Painful Nipple: A Rare Presentation for an Infiltrating Lobular Carcinoma. PMID- 26548446 TI - The determining factor of a preferred orientation of GaN domains grown on m-plane sapphire substrates. AB - Epitaxial lateral overgrowth in tandem with the first-principles calculation was employed to investigate the determining factor of a preferred orientation of GaN on SiO2-patterned m-plane sapphire substrates. We found that the (1100) orientation is favored over the (1103)-orientation in the region with a small filling factor of SiO2, while the latter orientation becomes preferred in the region with a large filling factor. This result suggests that the effective concentration determines the preferred orientation of GaN: the (1100)- and (1103) orientations preferred at their low and high concentrations, respectively. Our computational study revealed that at a low coverage of Ga and N atoms, the local atomic arrangement resembles that on the (1103) surface, although the (1100) surface is more stable at their full coverage. Such a (1103)-like atomic configuration crosses over to the local structure resembling that on the (1100) surface as the coverage increases. Based on results, we determined that high effective concentration of Ga and N sources expedites the growth of the (1103) orientation while keeping from transition to the (1100)-orientation. At low effective concentration, on the other hand, there is a sufficient time for the added Ga and N sources to rearrange the initial (1103)-like orientation to form the (1100)-orientation. PMID- 26548447 TI - Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa. AB - Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection. PMID- 26548448 TI - Regulation of nitrogen metabolism in the nitrate-ammonifying soil bacterium Bacillus vireti and evidence for its ability to grow using N2 O as electron acceptor. AB - Bacillus vireti is a nitrate-ammonifying bacterium and a partial denitrifier, reducing NO3 (-) , NO2 (-) , NO and N2 O with NarG, NrfA, CbaA and NosZ respectively. Growth is optimized through successive use of the electron acceptors O2 and NO3 (-) , followed by NO2 (-) , NO and N2 O. Fermentation takes place simultaneously with anaerobic respiration. When grown in batch culture with 5 mM initial NO3 (-) , transcription of nrfA was high and most NO3 (-) was reduced to NH4 (+) . With 20 mM initial NO3 (-) , nrfA transcription was lower and more than 50% of the nitrate was recovered as NO, N2 O and N2 . Analysis of gene transcription patterns and corresponding gas kinetics indicated that O2 and NO2 (-) or NO are main controllers of nrfA, nirB, cbaA and nosZ transcription. This was corroborated by analyses of putative binding regions for specific transcriptional regulators. Furthermore, we demonstrate that N2 O reduction in B. vireti supports growth. The high nosZ transcription but low N2 O production seen at 5 mM NO3 (-) implies that this organism can use N2 O reductase to scavenge N2 O from other organisms in the soil, thus possibly acting as a net sink for N2 O. PMID- 26548449 TI - Effect of a third-generation LED LCU on microhardness of tooth-colored restorative materials. AB - OBJECTIVE: To assess the effects of different modes of a third-generation light curing unit (LCU) (VALO) on the microhardness of restorative materials. DESIGN: A microhybrid composite resin (Filtek(TM) Z550), a giomer (Beautifil II), a compomer (Dyract eXtra) and a RMGIC (Photac(TM) Fil) were used in the study. Three different modes of VALO were tested and a second-generation LCU (Elipar S10) was used as a control. The microhardness (VHN) was measured using a Vickers Hardness tester. Data were analyzed using two-way anova and post hoc Tukey's test (P < 0.05). RESULTS: The Filtek Z550 group had the highest VHN values followed by Photac Fil, Beautifil II and the Dyract eXtra at both top and bottom surfaces, however the difference between Filtek Z550 and Photac Fil was not statistically significant for the bottom surfaces (P > 0.05). Of the different curing protocols tested, the VALO LCU in Mode 3 resulted in the lowest VHN values at both top and bottom surfaces (P < 0.05). CONCLUSION: Based on the results of this study, it can be concluded that the high-power mode of the VALO LCU can be recommended for clinical applications especially in pediatric patients, as it can shorten the time required to adequately polymerize resin-based tooth-colored restorative materials. PMID- 26548450 TI - Synthetic Developments of Nontoxic Quantum Dots. AB - Semiconductor nanocrystals, or quantum dots (QDs), are candidates for biological sensing, photovoltaics, and catalysis due to their unique photophysical properties. The most studied QDs are composed of heavy metals like cadmium and lead. However, this engenders concerns over heavy metal toxicity. To address this issue, numerous studies have explored the development of nontoxic (or more accurately less toxic) quantum dots. In this Review, we select three major classes of nontoxic quantum dots composed of carbon, silicon and Group I-III-VI elements and discuss the myriad of synthetic strategies and surface modification methods to synthesize quantum dots composed of these material systems. PMID- 26548451 TI - Cytosolic phospholipase A2 alpha has a crucial role in the pathogenesis of DSS induced colitis in mice. AB - Colitis, an inflammation of the colon, is a well-characterized massive tissue injury. Cytosolic phospholipase A2 alpha (cPLA2 alpha) upregulation plays an important role in the development of several inflammatory diseases. The aim of the present study was to define the role of cPLA2 alpha upregulation in the development of colitis. We used a mouse model of dextran sulfate sodium induced colitis. Immunoblotting analysis showed that cPLA2 alpha and NF-kappaB were upregulated and activated in the colon from day 2 of colitis induction. This molecular event preceded the development of the disease, as determined by Disease Activity Index score, body weight, colon length, and the expression of colonic inflammatory markers, including neutrophil infiltration detected by myeloperoxidase and by NIMP-R14, ICAM-1, COX-2, iNOS upregulation and LTB4 and TNF-alpha secretion. Prevention of cPLA2 alpha upregulation and activity in the colon by i.v. administration of specific antisense oligonucleotides against cPLA2 alpha 1 day prior and every day of exposure to dextran sulfate sodium significantly impeded the development of the disease and prevented NF-kappaB activation, neutrophils infiltration into the colonic mucosa, and expression of proinflammatory proteins in the colon. Our results demonstrate a critical role of cPLA2 alpha upregulation in inflammation and development of murine colitis. PMID- 26548452 TI - Anti-inflammatory and anti-osteoclastogenic effects of zinc finger protein A20 overexpression in human periodontal ligament cells. AB - BACKGROUND AND OBJECTIVE: Although overexpression of the nuclear factor kappaB inhibitory and ubiquitin-editing enzyme A20 is thought to be involved in the pathogenesis of inflammatory diseases, its function in periodontal disease remains unknown. The aims of the present study were to evaluate A20 expression in patients with periodontitis and to study the effects of A20 overexpression, using a recombinant adenovirus encoding A20 (Ad-A20), on the inflammatory response and on osteoclastic differentiation in lipopolysaccharide (LPS)- and nicotine stimulated human periodontal ligament cells (hPDLCs). MATERIAL AND METHODS: The concentration of prostaglandin E2 was measured by radioimmunoassay. Reverse transcription-polymerase chain reactions and western blot analyses were used to measure mRNA and protein levels, respectively. Osteoclastic differentiation was assessed in mouse bone marrow-derived macrophages using conditioned medium from LPS- and nicotine-treated hPDLCs. RESULTS: A20 was upregulated in the gingival tissues and neutrophils from patients with periodontitis and in LPS- and nicotine exposed hPDLCs. Pretreatment with A20 overexpression by Ad-A20 markedly attenuated LPS- and nicotine-induced production of prostaglandin E2 , as well as expression of cyclooxygenase-2 and proinflammatory cytokines. Moreover, A20 overexpression inhibited the number and size of tartrate-resistant acid phosphatase-stained osteoclasts, and downregulated osteoclast-specific gene expression. LPS- and nicotine-induced p38 phosphorylation and nuclear factor kappaB activation were blocked by Ad-A20. Ad-A20 inhibited the effects of nicotine and LPS on the activation of pan-protein kinase C, Akt, GSK-3beta and protein kinase Calpha. CONCLUSIONS: This study is the first to demonstrate that A20 overexpression has anti-inflammatory effects and blocks osteoclastic differentiation in a nicotine- and LPS-stimulated hPDLC model. Thus, A20 overexpression may be a potential therapeutic target in inflammatory bone loss diseases, such as periodontal disease. PMID- 26548453 TI - An Elicited-Production Study of Inflectional Verb Morphology in Child Finnish. AB - Many generativist accounts (e.g., Wexler, 1998) argue for very early knowledge of inflection on the basis of very low rates of person/number marking errors in young children's speech. However, studies of Spanish (Aguado-Orea & Pine, 2015) and Brazilian Portuguese (Rubino & Pine, 1998) have revealed that these low overall error rates actually hide important differences across the verb paradigm. The present study investigated children's production of person/number marked verbs by eliciting present tense verb forms from 82 native Finnish-speaking children aged 2;2-4;8 years. Four main findings were observed: (a) Rates of person/number marking errors were higher in low-frequency person/number contexts, even excluding children who showed no evidence of having learned the relevant morpheme, (b) most errors involved the use of higher frequency forms in lower frequency person/number contexts, (c) error rates were predicted not only by the frequency of person/number contexts (e.g., 3sg > 2pl) but also by the frequency of individual "ready-inflected" lexical target forms, and (d) for low-frequency verbs, lower error rates were observed for verbs with high phonological neighborhood density. It is concluded that any successful account of the development of verb inflection will need to incorporate both (a) rote-storage and retrieval of individual inflected forms and (b) phonological analogy across them. PMID- 26548454 TI - A systematic survey of the integration of animal behavior into conservation. AB - The role of behavioral ecology in improving wildlife conservation and management has been the subject of much recent debate. We sought to answer 2 foundational questions about the current use of behavioral knowledge in conservation: To what extent is behavioral knowledge used in wildlife conservation and management, and how does the use of animal behavior differ among conservation fields in both frequency and types of use? We searched the literature for intersections between key fields of animal behavior and conservation and created a systematic heat map (i.e., graphical representation of data where values are represented as colors) to visualize relative efforts. Some behaviors, such as dispersal and foraging, were commonly considered (mean [SE] of 1147.38 [353.11] and 439.44 [108.85] papers per cell, respectively). In contrast, other behaviors, such as learning, social, and antipredatory behaviors were rarely considered (mean [SE] of 33.88 [7.62], 44.81 [10.65], and 22.69 [6.37] papers per cell, respectively). In many cases, awareness of the importance of behavior did not translate into applicable management tools. Our results challenge previous suggestions that there is little association between the fields of behavioral ecology and conservation and reveals tremendous variation in the use of different behaviors in conservation. We recommend that researchers focus on examining underutilized intersections of behavior and conservation themes for which preliminary work shows a potential for improving conservation and management, translating behavioral theory into applicable and testable predictions, and creating systematic reviews to summarize the behavioral evidence within the behavior-conservation intersections for which many studies exist. PMID- 26548455 TI - Defect-Controlled Preparation of UiO-66 Metal-Organic Framework Thin Films with Molecular Sieving Capability. AB - Metal-organic framework (MOF) UiO-66 thin films are solvothermally grown on conducting substrates. The as-synthesized MOF thin films are subsequently dried by a supercritical process or treated with polydimethylsiloxane (PDMS). The obtained UiO-66 thin films show excellent molecular sieving capability as confirmed by the electrochemical studies for redox-active species with different sizes. PMID- 26548457 TI - Magnetic structures of R5Ni2In4 and R11Ni4In9 (R = Tb and Ho): strong hierarchy in the temperature dependence of the magnetic ordering in the multiple rare-earth sublattices. AB - The magnetic properties and magnetic structures of the R 5Ni2In4 and the microfibrous R 11Ni4In9 compounds with R = Tb and Ho have been examined using magnetization, heat capacity, and neutron diffraction data. Rare earth atoms occupy three and five symmetrically inequivalent rare earth sites in R 5Ni2In4 and R 11Ni4In9 compounds, respectively. As a result of the intra- and inter magnetic sublattice interactions, the magnetic exchange interactions are different for various rare earth sites; this leads to a cascade of magnetic transitions with a strong hierarchy in the temperature dependence of the magnetic orderings. A transition at T C = 125 K in Tb5Ni2In4 [kappa 1 = (0, 0, 0)] leads to a ferro/ferrimagnetic order where the magnetic ordering in one of the three R-sublattices leads to the ordering of another one; the third sublattice stays non-magnetic. New magnetic Bragg peaks appearing below T N = 20 K can be indexed with the incommensurate magnetic propagation vector kappa 2 = (0, 0.636, 1/2); at T N = 20 K a cycloidal spin order, which acts mostly upon the third R-sublattice, occurs. Ho5Ni2In4 establishes first antiferromagnetism [kappa = (0, 0, 0)] at T N = 31 K on two R-sublattices; then the system becomes ferro/ferrimagnetic at T C = 25 K with the third sublattice ordering as well. Tb11Ni4In9 has three magnetic transitions at T C = 135 K, T N1 = 35 K and at T N2 = 20 K; they are respectively coupled to the appearance of different propagation vectors [kappa 1 = (0, 0, 0), kappa 2 = (0, 0, 1/2), kappa 3 = (0, 1, 1/2)], which themselves are operating differently on the five different R sublattices. Two sublattices remain mostly ferromagnetic down to lowest temperature while the three others are predominantly coupled antiferromagnetically. In Ho11Ni4In9 a purely antiferromagnetic order, described by four different magnetic propagation vectors [kappa 1 = (0, 0.62, 0), kappa 2 = (0, 1, 0), kappa 3 = (0, 0, 1/2), kappa 4 = (0, 1, 1/2)], succeedingly includes all five different sublattices on cooling through transitions at T N1 = 22 K, T N2 = 12 K, T N3 = 8 K and T N4 = 7 K. The strength of the magnetic interactions of the different sublattices can be linked to structural details for both R 5Ni2In4 and R 11Ni4In9 compounds. PMID- 26548456 TI - Intrinsic Motivation and Achievement in Mathematics in Elementary School: A Longitudinal Investigation of Their Association. AB - This study examined the associations between intrinsic motivation and achievement in mathematics in a sample of 1,478 Canadian school-age children followed from Grades 1 to 4 (ages 7-10). Children self-reported their intrinsic motivation toward mathematics, whereas achievement was measured through direct assessment of mathematics abilities. Cross-lagged models showed that achievement predicted intrinsic motivation from Grades 1 to 2, and from Grades 2 to 4. However, intrinsic motivation did not predict achievement at any time. This developmental pattern of association was gender invariant. Contrary to the hypothesis that motivation and achievement are reciprocally associated over time, our results point to a directional association from prior achievement to subsequent intrinsic motivation. Results are discussed in light of their theoretical and practical implications. PMID- 26548458 TI - Are Fluorescent Organic Nanoparticles Relevant Tools for Tracking Cancer Cells or Macrophages? AB - Strongly solvatochromic fluorophores are devised, containing alkyl chains and enable to self-assemble as very bright fluorescent organic nanoparticles (FONs) in water (Phif = 0.28). The alkyl chains impart each fluorophore with strongly hydrophobic surroundings, causing distinct emission colors between FONs where the fluorophores are associated, and their disassembled state. Such color change is harnessed to assess the long-term fate of FONs in both cancer cells and monocytes/macrophages. Disintegration of the orange-emitting FONs by monocytes/macrophages is evidenced through the formation of micrometer green yellowish emitting vesicles. By contrast, cancer cells retain longer the integrity of organic nanoparticles. In both cases, no significant toxicity is detected, making FONs as valuable bioimaging agents for cell tracking with weak risks of deleterious accumulation and low degradation rate. PMID- 26548459 TI - The origins of word learning: Brain responses of 3-month-olds indicate their rapid association of objects and words. AB - The present study explored the origins of word learning in early infancy. Using event-related potentials (ERP) we monitored the brain activity of 3-month-old infants when they were repeatedly exposed to several initially novel words paired consistently with each the same initially novel objects or inconsistently with different objects. Our results provide strong evidence that these young infants extract statistic regularities in the distribution of the co-occurrences of objects and words extremely quickly. The data suggest that this ability is based on the rapid formation of associations between the neural representations of objects and words, but that the new associations are not retained in long-term memory until the next day. The type of brain response moreover indicates that, unlike in older infants, in 3-month-olds a semantic processing stage is not involved. Their ability to combine words with meaningful information is caused by a primary learning mechanism that enables the formation of proto-words and acts as a precursor for the acquisition of genuine words. PMID- 26548460 TI - Effect of the Metal on Disulfide/Thiolate Interconversion: Manganese versus Cobalt. AB - It has recently been proposed that disulfide/thiolate interconversion supported by transition-metal ions is involved in several relevant biological processes. In this context, the present contribution represents a unique investigation of the effect of the coordinated metal (M) on the M(n+)-disulfide/M((n+1)+)-thiolate switch properties. Like its isostructural Co(II)-based parent compound, Co(II)2SS (Angew. Chem. Int. Ed.- 2014, 53, 5318), the new dinuclear disulfide-bridged Mn(II) complex Mn(II)2SS can undergo an M(II)-disulfide/M(III)-thiolate interconversion, which leads to the first disulfide/thiolate switch based on Mn. The coordination of iodide to the metal ion stabilizes the oxidized form, as the disulfide is reduced to the thiolate. The reverse process, which involves the reduction of M(III) to M(II) with the concomitant oxidation of the thiolates, requires the release of iodide. The Mn(II)2SS complex slowly reacts with Bu4NI in CH2Cl2 to afford the mononuclear Mn(III)-thiolate complex Mn(III)I. The process is much slower (ca. 16 h) and much less efficient (ca. 30% yield) with respect to the instantaneous and quantitative conversion of Co(II)2SS into Co(III)I under similar conditions. This distinctive behavior can be rationalized by considering the different electrochemical properties of the involved Co and Mn complexes and the DFT-calculated driving force of the disulfide/thiolate conversion. For both Mn and Co systems, M(II)-disulfide/M(III)-thiolate interconversion is reversible. However, when the iodide is removed with Ag(+), the M(II)2SS complexes are regenerated, albeit much slower for Mn than for Co systems. PMID- 26548461 TI - All-trans retinoic acid inhibits proliferation, migration, invasion and induces differentiation of hepa1-6 cells through reversing EMT in vitro. AB - Hepatocellular carcinoma (HCC) has the characristics of tumor invasiveness, frequent intrahepatic spread and extra hepatic metastases, which affects the therapy efficiency and prognosis. Epithelial-mesenchymal transition (EMT) is now recognized as a key process in tumor invasion, metastasis and the generation of cancer initiating cells. All-trans retinoic acid (ATRA) is currently used as a potential chemo-therapeutic or chemo-preventive agent because of its anti proliferative, pro-apoptotic and antioxidant properties. This study investigated the effects of ATRA at different concentrations on the proliferation, migration, invasion, differentiation and functions of the mouse hepa1-6 hepatocarcinoma cell line and explored whether ATRA regulates EMT in the antitumor process. Trypan blue staining and colony formation assay were used to detect cell proliferation. Wound-healing assay and Transwell Matrigel assay were performed to examine migration. Invasion was assessed by using Transwell invasion assay. In the present study, ATRA significantly inhibited the cell growth, colony formation, migration, and invasion capability of hepa1-6 cells in a dose-dependent manner. Furthermore, ATRA at low concentration (0.1 umol/l) could generate these influences. After treated in the ATRA medium, the expression of mature hepatic markers ALB (albumin), CK18 (cytokeratin 18), TAT (tyrosine aminotransferase), ApoB (apolipoprotein B) decreased and that of hepatocarcinoma marker AFP (alpha fetoprotein) increased. At day 7 after ATRA induction, hepa1-6 cells showed comparable indocyanine green (ICG) uptake and glycogen storage function to the blank control. The mRNA expression of mesenchymal markers N-cadherin, vimentin, snail and twist decreased, while expression of epithelial marker E-cadherin increased in hepa1-6 cells after treated with ATRA. Therefore, this study demonstrates that ATRA remarkably suppressed the proliferation, migration, invasion of hepa1-6 hepatocarcinoma cell line and effectively induced its differentiation and liver functions in vitro through the reversal of EMT. HCC may be more sensitive to ATRA than other cancers, suggesting the prospective usefulness of ATRA in the treatment of HCC. PMID- 26548462 TI - Triggering prepared actions by sudden sounds: reassessing the evidence for a single mechanism. AB - Loud acoustic stimuli can unintentionally elicit volitional acts when a person is in a state of readiness to execute them (the StartReact effect). It has been assumed that the same subcortical pathways and brain regions underlie all instances of the StartReact effect. They are proposed to involve the startle reflex pathways, and the eliciting mechanism is distinct from other ways in which sound can affect the motor system. We present an integrative review which shows that there is no evidence to support these assumptions. We argue that motor command generation for learned, volitional orofacial, laryngeal and distal limb movements is cortical and the StartReact effect for such movements involves transcortical pathways. In contrast, command generation for saccades, locomotor corrections and postural adjustments is subcortical and subcortical pathways are implicated in the StartReact effect for these cases. We conclude that the StartReact effect is not a special phenomenon mediated by startle reflex pathways, but rather is a particular manifestation of the excitatory effects of intense stimulation on the central nervous system. PMID- 26548463 TI - Youden's Index and the Weight of Evidence Revisited. AB - A correspondence between Youden's index for rating diagnostic tests and the log likelihood ratio of a positive test outcome is illustrated by data calculated from two previously-published studies of binary tests. PMID- 26548465 TI - Transformation kinetics of vapor-deposited thin film organic glasses: the role of stability and molecular packing anisotropy. AB - While ordinary glasses transform into supercooled liquid via a homogeneous bulk mechanism, thin film glasses of higher stability transform heterogeneously by a front propagating from the surface and/or the interfaces. In this work, we use quasi-adiabatic fast scanning nanocalorimetry to determine the heat capacity of thin glassy layers of indomethacin vapor-deposited in a broad temperature range of 110 K below the glass transition temperature. Their variation in fictive temperature amounts to 40 K. We show that a propagating front is the initial transformation mechanism in all cases. Using an ad hoc surface normalization procedure we determine the corresponding growth front velocity for the whole range of deposition temperatures. Although the transformation rate changes by a factor of 10 between the most and less stable samples, the relation between the mobility of the front and the thermodynamic stability of the glass is not uniquely defined. Glasses grown above 280 K, which are at equilibrium with the supercooled liquid, present a different dependence of the growth front velocity on fictive temperature compared to glasses grown out of equilibrium at Tdep < 250 K. These glasses transform faster with increasing Tf. Our data clarify previous reports and support the evidence that the fictive temperature alone is not an absolute indicator of the properties of the glass, at least when its structure is not completely isotropic. To interpret the data, we propose that the growth front velocity depends on three terms: the mobility of the liquid at a given temperature, the mobility of the glass and the arrangement of the molecules in the glass. PMID- 26548466 TI - Protein tetrazinylation via diazonium coupling for covalent and catalyst-free bioconjugation. AB - An efficient and bench-stable reagent was synthesized for direct and covalent introduction of tetrazines onto target protein or virus surfaces, which can be further modified based on tetrazine-ene ligation to achieve fluorescence labelling or PEGylation under mild conditions. PMID- 26548467 TI - [(18)F]-Group 13 fluoride derivatives as radiotracers for positron emission tomography. AB - The field of (18)F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [(18)F]-radiotracers were generated by the direct attachment of (18)F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an (18)F group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [(18)F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [(18)F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [(18)F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET. PMID- 26548468 TI - [The dangers of drug career in young people]. AB - It is significant when a young person encounters drugs for the first time. Research has shown that 70% of later addicts try the drugs during the five-year period of adolescence. Youngsters tend to try new experinces; they are high risk takers, seek novelty and are sensitive to pressure from the peer group. However, the juvenile central nervous system reacts differently when taking drugs, than it happens in an older age. Damage could occur on critical regions of the brain. Addictive drugs may give rise to changes in multiple system of memory, that could maintain the addiction for a long time. Drug use overrides and modifies the natural reward system, induces further drug-seeking, independently from the sensations of drug use. PMID- 26548469 TI - [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis]. AB - It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration. PMID- 26548470 TI - [Long-term follow-up after tympanostomy tube insertion in children with serous otitis media]. AB - INTRODUCTION: The authors report about the efficacy of inserted tympanostomy tube in children with serous otitis media. AIM: The aim of the authors was to assess the status of eardrum, the function of Eustachian tube and hearing level 10 years after the use of tympanostomy tube. METHOD: Patients filled out a questionnaire and microscopic examination of tympanic membrane, tympanometry, Eustachian tube function examination, and audiometry tests were performed. RESULTS: In the period of 2003-2004, ventilation tube insertion was performed in 711 patients in the ENT Department of Pediatric Health Center of University of Szeged. In 349 patients adenotomy and tympanostomy tube insertion, in 18 cases tonsillectomy and grommet insertion and in 344 patients only typmanostomy tube insertion were performed. Due to objective difficulties (address change, no phone number) 453 patients were asked for control test and 312 persons accepted the invitation. Normal hearing level was found in 84.6% of patients and normal tympanometry result occurred in 82%. Tympanic ventilation disorder, perforation of tympanic membrane, sensorineural hearing loss and sensorineural hearing loss due to noise exposure were diagnosed. CONCLUSIONS: Application of tympanostomy tube is effective in the treatment of serous otitis media resulting from ventilation disorder. The authors draw attention to the importance of tympanometry examination to prevent the adhesive processes and cholesteatoma in chronic ventilation disorder of the middle ear. PMID- 26548471 TI - [Sunitinib and zoledronic acid induced osteonecrosis of the jaw]. AB - The tendency for bisphosphonate and non-bisphosphonate (eg.: antiresorptive or anti-angiogenesis drugs) induced osteonecrosis is increasing. Treatment of these patients is a challenge both for dentists and for oral and maxillofacial surgeons. Cooperation with the drug prescribing general medicine colleagues to prevent osteonecrosis is extremely important. Furthermore, prevention should include dental focus elimination, oral hygienic instructions and education, dental follow-up and, in case of manifest necrosis, referral to maxillofacial departments. Authors outline the difficulties of conservative and surgical treatment of a patient with sunitinib and zoledronic acid induced osteonecrosis. The patient became symptomless and the operated area healed entirely six and twelve months postoperatively. A long term success further follow-up is necessary to verify long-term success. PMID- 26548472 TI - [Case and studies]. AB - Case studies and case reports form an important and ever growing part of scientific and scholarly literature. The paper deals with the share and citation rate of these publication types on different fields of research. In general, evidence seems to support the opinion that an excessive number of such publications may negatively influence the impact factor of the journal. In the literature of scientometrics, case studies (at least the presence of the term "case study" in the titles of the papers) have a moderate share, but their citation rate is practically equal to that of other publication types. PMID- 26548473 TI - [A "peculiar" doctor - Karoly Brancsik (1842-1915), the chief physician of Trecsen County]. PMID- 26548475 TI - Allium Discoloration: Color Compounds Formed during Pinking of Onion and Leek. AB - Structures and formation pathways of compounds responsible for pink discoloration of onion and leek were studied. A procedure was developed for the isolation and purification of the color compounds from various model systems and their identification by HPLC-DAD-MS/MS. In total, structures of 15 major color compounds were tentatively determined. It was found that the pigment is a complex mixture of highly conjugated species composed of two N-substituted 3,4 dimethylpyrrole-derived rings linked by either a methine or a propenylidine bridge. These two-ring units are further modified by various C1- and C3-side chains. Experiments with isotope-labeled thiosulfinates revealed that the methine bridge and C1-side chains originate from the methyl group of methiin, whereas the C3 units are derived from the propenyl group of isoalliin. PMID- 26548476 TI - Substrate-controlled Rh(II)-catalyzed single-electron-transfer (SET): divergent synthesis of fused indoles. AB - Rh(II)-catalyzed diversified ring expansions controlled by single-electron transfer (SET) have been disclosed in this communication, producing a series of indole-fused azetidines and 1H-carbazoles or related derivatives in moderate to good yields via Rh2(III,II) nitrene radical intermediates. The direction of ring expansion branches according to different ring sizes of methylenecycloalkanes. PMID- 26548477 TI - Microsecond-Scale MD Simulations of HIV-1 DIS Kissing-Loop Complexes Predict Bulged-In Conformation of the Bulged Bases and Reveal Interesting Differences between Available Variants of the AMBER RNA Force Fields. AB - We report an extensive set of explicit solvent molecular dynamics (MD) simulations (~25 MUs of accumulated simulation time) of the RNA kissing-loop complex of the HIV-1 virus initiation dimerization site. Despite many structural investigations by X-ray, NMR, and MD techniques, the position of the bulged purines of the kissing complex has not been unambiguously resolved. The X-ray structures consistently show bulged-out positions of the unpaired bases, while several NMR studies show bulged-in conformations. The NMR studies are, however, mutually inconsistent regarding the exact orientations of the bases. The earlier simulation studies predicted the bulged-out conformation; however, this finding could have been biased by the short simulation time scales. Our microsecond-long simulations reveal that all unpaired bases of the kissing-loop complex stay preferably in the interior of the kissing-loop complex. The MD results are discussed in the context of the available experimental data and we suggest that both conformations are biochemically relevant. We also show that MD provides a quite satisfactory description of this RNA system, contrasting recent reports of unsatisfactory performance of the RNA force fields for smaller systems such as tetranucleotides and tetraloops. We explain this by the fact that the kissing complex is primarily stabilized by an extensive network of Watson-Crick interactions which are rather well described by the force fields. We tested several different sets of water/ion parameters but they all lead to consistent results. However, we demonstrate that a recently suggested modification of van der Waals interactions of the Cornell et al. force field deteriorates the description of the kissing complex by the loss of key stacking interactions stabilizing the interhelical junction and excessive hydrogen-bonding interactions. PMID- 26548478 TI - Synthesis of NiO Nanofibers Composed of Hollow Nanospheres with Controlled Sizes by the Nanoscale Kirkendall Diffusion Process and Their Electrochemical Properties. AB - NiO nanofibers composed of hollow NiO nanospheres with different sizes were prepared by electrospinning method. The mean size of the hollow NiO nanospheres was determined by the mean size of the Ni nanocrystals of the Ni-C composite nanofibers formed as an intermediate product. Porous-structured NiO nanofibers were also prepared as a comparison sample by direct oxidation of the electrospun nanofibers. The discharge capacities of the nanofibers composed of hollow nanospheres reduced at 300, 500, and 700 degrees C for the 250th cycle were 707, 655, and 261 mA h g(-1), respectively. However, the discharge capacity of the porous-structured NiO nanofibers for the 250th cycle was low as 206 mA h g(-1). The nanofibers composed of hollow nanospheres had good structural stability during cycling. PMID- 26548479 TI - Cooperative Chemisorption-Induced Physisorption of CO2 Molecules by Metal-Organic Chains. AB - Effective CO2 capture and reduction can be achieved through a molecular scale understanding of interaction of CO2 molecules with chemically active sites and the cooperative effects they induce in functional materials. Self-assembled arrays of parallel chains composed of Au adatoms connected by 1,4-phenylene diisocyanide (PDI) linkers decorating Au surfaces exhibit self-catalyzed CO2 capture leading to large scale surface restructuring at 77 K (ACS Nano 2014, 8, 8644-8652). We explore the cooperative interactions among CO2 molecules, Au-PDI chains and Au substrates that are responsible for the self-catalyzed capture by low temperature scanning tunneling microscopy (LT-STM), X-ray photoelectron spectroscopy (XPS), infrared reflection absorption spectroscopy (IRAS), temperature-programmed desorption (TPD), and dispersion corrected density functional theory (DFT). Decorating Au surfaces with Au-PDI chains gives the interfacial metal-organic polymer characteristics of both a homogeneous and heterogeneous catalyst. Au-PDI chains activate the normally inert Au surfaces by promoting CO2 chemisorption at the Au adatom sites even at <20 K. The CO2(delta-) species coordinating Au adatoms in-turn seed physisorption of CO2 molecules in highly ordered two-dimensional (2D) clusters, which grow with increasing dose to a full monolayer and, surprisingly, can be imaged with molecular resolution on Au crystal terraces. The dispersion interactions with the substrate force the monolayer to assume a rhombic structure similar to a high-pressure CO2 crystalline solid rather than the cubic dry ice phase. The Au surface supported Au-PDI chains provide a platform for investigating the physical and chemical interactions involved in CO2 capture and reduction. PMID- 26548480 TI - Research Techniques Made Simple: Drug Delivery Techniques, Part 1: Concepts in Transepidermal Penetration and Absorption. PMID- 26548481 TI - The FDA: Doctors, Investigators, and Translational Research. PMID- 26548485 TI - Melanoma Incidence and Lethality Is Increased Following Solid Organ Transplantation. AB - Organ transplants save lives, but the risks of adverse health outcomes remain high. Robbins et al. (2015) report the findings of a record-linkage study that followed almost 140,000 organ transplant recipients (OTRs) for melanoma. They found higher risk of incident melanoma among OTRs and markedly increased lethality. Education and surveillance are key to mitigating these effects. PMID- 26548486 TI - CYR61/CCN1: A Novel Mediator of Epidermal Hyperplasia and Inflammation in Psoriasis? AB - The complex pathogenesis of psoriasis is still not fully understood. The study by Sun et al. (2015) suggests that CYR61 (now named CCN1), a secreted matricellular protein, has a role in the pathogenesis of psoriasis, and thus targeting CCN1 represents a potential therapeutic strategy in its treatment. PMID- 26548487 TI - Down-RANKing the Threat of HSV-1: RANKL Upregulates MHC-Class-I-Restricted Anti Viral Immunity in Herpes Simplex Virus Infection. AB - Herpes simplex virus (HSV-1) is a major cause of viral skin infection in humans. Klenner and colleagues now show that the epidermal receptor activator of NFkappaB ligand (RANKL) is critical for the induction of anti-viral CD8(+) effector T cells (CTL) during cutaneous HSV-1 infection. Activation via RANKL prevents Langerhans cell apoptosis, thus leading to enhanced antigen transport to regional lymph nodes, increasing the CTL-priming capacity of lymph node dendritic cells. PMID- 26548488 TI - Bad Hair Day: Testosterone and Wnts. AB - Androgens have an important role in normal skin physiology, as well as in the pathogenesis of many skin conditions, such as acne vulgaris, hirsutism, and androgenic alopecia. Kretzchumar et al. (2015) investigate the relationship between androgen receptor (AR) signaling and beta-catenin/Wnt signaling pathways in murine hair follicles. PMID- 26548489 TI - Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix. AB - Fibroblasts have a central role in wound healing via matrix production, remodeling, and contraction. Their role as mechanoresponsive cells during tissue repair is evident, but the molecular mechanisms of this process remain uncertain. Filamin A, an intracellular protein that stabilizes the actin cytoskeleton regulates fibroblast-matrix interactions. Fibroblast defects in cytoskeletal dynamics may underlie key aspects of chronic wound pathophysiology. PMID- 26548490 TI - Cells to Surgery Quiz: November 2015. PMID- 26548491 TI - November 2015 Snapshot Dx Quiz: Linking Science to Patient Care. PMID- 26548492 TI - New oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1. AB - Human apurinic/apyrimidinic endonuclease APE1 is one of the key enzymes of the base excision DNA repair system. The main biological function of APE1 is the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. It has long been known that AP-sites have mutagenic and cytotoxic effects and their accumulation in DNA is a potential hazard to the cell lifecycle. The structural and biochemical studies of APE1 are complicated by its high catalytic activity towards the AP-site and its cyclic or acyclic analogues. This work has focussed on the design, synthesis and analysis of oligonucleotide derivatives as potentially unreactive APE1 substrates. We have shown that the replacement of oxygen atoms in the phosphate group on the 5'-side from the AP-site analogue tetrahydrofuran (F) considerably decreases the rate of enzymatic hydrolysis of modified oligonucleotides. We have calculated that a N3'-P5' phosphoramidate linkage is hydrolysed about 30 times slower than the native phosphodiester bond while phosphorothioate or primary phosphoramidate linkages are cleaved more than three orders of magnitude slower. The value of IC50 of the oligonucleotide duplex containing a primary phosphoramidate linkage is 2.5 * 10(-7) M, which is in accordance with the APE1 association constant of DNA duplexes containing AP sites. Thus, it is demonstrated that oligonucleotide duplexes with chemical modifications could be used as unreactive substrates and potential competitive inhibitors of APE1. PMID- 26548493 TI - Spoof surface plasmon polaritons in terahertz transmission through subwavelength hole arrays analyzed by coupled oscillator model. AB - Both the localized resonance and excitation of spoof surface plasmon polaritons are observed in the terahertz transmission spectra of periodic subwavelength hole arrays. Analyzing with the coupled oscillator model, we find that the terahertz transmission is actually facilitated by three successive processes: the incident terahertz field first initiates the localized oscillation around each hole, and then the spoof surface plasmon polaritons are excited by the localized resonance, and finally the two resonances couple and contribute to the transmission. Tailoring the localized resonance by hole size, the coupling strength between spoof surface plasmon polaritons and localized resonances is quantitatively extracted. The hole size dependent transmittance and the coupling mechanism are further confirmed by fitting the measured spectra to a modified multi-order Fano model. PMID- 26548494 TI - The behavioral profile of spice and synthetic cannabinoids in humans. AB - The use of synthetic cannabinoids (spice) is increasing. The number of descriptions of (new) clinical side effects is also increasing. We screened relevant publications for articles about spice with a focus on the clinical manifestations of the use of this drug. Spice creates diffuse psychiatric and somatic effects that are only partially similar to those of natural cannabinoids. Most of the observed effects are related to sympathomimetic-cardiac effects and neuropsychiatric manifestations. Clinical treatment is primarily based on intensive apparative and laboratory monitoring and supportive therapy. Because the exact active ingredients of spice are often difficult to determine with standard specific toxicology testing, the assessment and analysis of consumed substances by specialized laboratories is recommended. PMID- 26548495 TI - Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia. AB - Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. PMID- 26548496 TI - Deaths from necrotizing fasciitis in the United States, 2003-2013. AB - Necrotizing fasciitis (NF) is a life-threatening infection requiring urgent surgical and medical therapy. Our objective was to estimate the mortality burden of NF in the United States, and to identify time trends in the incidence rate of NF-related mortality. We obtained data from the National Center for Health Statistics, which receives information from death certificates from all states, including demographic information and cause of death. The U.S. Multiple Cause of Death Files were searched from 2003 to 2013 for a listing of NF (ICD-10 code M72.6) as either the underlying or contributing cause of death. We identified a total of 9871 NF-related deaths in the United States between 2003 and 2013, corresponding to a crude mortality rate of 4.8 deaths/1,000,000 person-years, without a significant time trend. Compared to white individuals, the incidence rate of NF-associated death was greater in black, Hispanic, and American Indian individuals, and lower in Asian individuals. Streptococcal infection was most commonly identified in cases where a pathogen was reported. Diabetes mellitus and obesity were more commonly observed in NF-related deaths compared to deaths due to other causes. Racial differences in the incidence of NF-related deaths merits further investigation. PMID- 26548497 TI - A novel homozygous insertion and review of published mutations in the NNT gene causing familial glucocorticoid deficiency (FGD). AB - Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by low levels of cortisol despite high adrenocorticotropin (ACTH) levels, due to the reduced ability of the adrenal cortex to produce cortisol in response to stimulation by ACTH. FGD is a heterogeneous disorder for which causal mutations have been identified in MC2R, MRAP, MCM4 and TXNRD2. Also mutations in STAR and CYP11A1 can sometimes present with a phenotype resembling FGD. Recently, it has been indicated that FGD can also be caused by mutations in NNT (nicotinamide nucleotide transhydrogenase). We identified a 6.67 Mb homozygous region harboring the NNT gene by SNP haplotyping in a 1-year old Dutch boy presenting with FGD, but without mutations in MC2R and MRAP. Exome-sequencing revealed a novel homozygous mutation (NM_012343.3: c.1259dupG) in NNT that was predicted to be disease-causing. The mutation is located in exon 9 and creates a frameshift leading to a premature stop-codon (p.His421Serfs*4) that is known to result in FGD. Both parents were shown to be heterozygous carriers. We reviewed the literature for all the reported NNT mutations and their clinical presentation. The median age of disease onset in 23 reported patients, including the present patient, was 12 months (range 3 days-39 months). There was no difference in age of disease onset between truncating and non-truncating NNT mutations. Based on recent literature, we advise to monitor patients with FGD due to NNT mutations for possible combined mineralocorticoid insufficiency and extra adrenal manifestations. PMID- 26548498 TI - Spinal muscular atrophy type III: Molecular genetic characterization of Turkish patients. AB - Spinal Muscular Atrophy (SMA) is a neurodegenerative disease with autosomal recessive inheritance. Homozygous loss of exon 7 of the Survival of motor neuron 1 (SMN1) gene is the main cause of SMA. Although progressive muscle weakness and atrophy are common symptoms, disease severity varies from severe to mild. Type III is one of the milder and less frequent forms of SMA. In this study, we report molecular genetic characteristics of 24 Turkish type III SMA patients. Homozygous loss of SMN1 exon 7 and 8 was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex ligation dependent probe amplification (MLPA). SMN2, homologue of SMN1, and Neuronal apoptosis inhibitory protein (NAIP) genes were also evaluated considering their influence on disease severity. We determined that male patients who were born in consanguineous families were predominant in our cohort and these patients mostly carry the homozygous loss of SMN1 exon 7 and 8 and four copies of SMN2 gene without NAIP deletions. PMID- 26548499 TI - Understanding Oestrogen Receptor Function in Breast Cancer and its Interaction with the Progesterone Receptor. New Preclinical Findings and their Clinical Implications. PMID- 26548501 TI - Chewing unflavored gum does not reduce cortisol levels during a cognitive task but increases the response of the sympathetic nervous system. AB - OBJECTIVES: Stress might be caused by various lifestyle factors and physical challenges and can result in severe diseases. The body responds to stressful events by release of hormones, like cortisol, as well as reaction of the sympathetic nervous system. One strategy to counteract stress is chewing gum. The present study aimed at investigating the influence of mastication on biomarkers of stress during performance of a stress test. METHODS: A two-armed cross-over study with 40 young male volunteers was performed. Hormone plasma concentrations were determined after an initial resting phase (2:30p.m.), immediately before (3:00p.m.) and two times after (3:20, 3:50p.m.) performance of a multitasking test using magnetic beads and ELISA methods. In addition, visual analog scales were used to rate subjective mood and the breathing and heart rates were monitored throughout the entire study period using a sensor chest belt. RESULTS: Performance of the stress test led to an increase in plasma cortisol concentrations from 223+/-23.3 to 325+/-38.4ng/ml (p=0.023) and caused changes in subjective mood ratings as well as breathing rates. Although chewing gum base had no impact on the plasma hormone concentrations, it induced a stronger elevation of average heart rates compared to not chewing (p=0.016). DISCUSSION: The effect of chewing gum on a mild stress load was less pronounced than in previous studies. Besides the detection of cortisol in saliva, not in plasma, in previous studies, flavored gum was used. Aroma active compounds might have substantially contributed to the beneficial effects of gum on biomarker of stress shown before. PMID- 26548502 TI - Pore-level mechanics of foam generation and coalescence in the presence of oil. AB - The stability of foam in porous media is extremely important for realizing the advantages of foamed gas on gas mobility reduction. Foam texture (i.e., bubbles per volume of gas) achieved is dictated by foam generation and coalescence processes occurring at the pore-level. For foam injection to be widely applied during gas injection projects, we need to understand these pore-scale events that lead to foam stability/instability so that they are modeled accurately. Foam flow has been studied for decades, but most efforts focused on studying foam generation and coalescence in the absence of oil. Here, the extensive existing literature is reviewed and analyzed to identify open questions. Then, we use etched-silicon micromodels to observe foam generation and coalescence processes at the pore-level. Special emphasis is placed on foam coalescence in the presence of oil. For the first time, lamella pinch-off as described by Myers and Radke [40] is observed in porous media and documented. Additionally, a new mechanism coined "hindered generation" is found. Hindered generation refers to the role oil plays in preventing the successful formation of a lamella following snap-off near a pore throat. PMID- 26548500 TI - The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats. AB - Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.v. nicotine self-administration (NSA), in which rats lever pressed for chow, sucrose, and nicotine under concurrent fixed-ratio (FR) 1 schedules. Male rats were assigned to one of three groups that differed in food and drug availability. The Nicotine C+S group had concurrent access to nicotine, chow, and sucrose. The Saline C+S group had access to saline, chow, and sucrose. The Nicotine C-Only group had access to nicotine and chow, but not sucrose. Changes in food intake and weight gain were assessed during baseline, NSA, and nicotine withdrawal (i.e., saline extinction). Weight gain was significantly slowed during NSA and increased during withdrawal, but did not differ between the nicotine groups. NSA produced a significant decrease in both chow and sucrose intake. Gradual tolerance to nicotine's effects on sucrose, but not chow intake, occurred. During withdrawal, chow and sucrose intake increased, with a larger percent increase in sucrose intake compared to chow. The proportion of total food intake from sucrose was greater at the end of withdrawal compared to baseline, indicating a history of nicotine intake changed dietary preference. Combined, these results indicate that sucrose intake is more resistant to nicotine's appetite suppressant effects and withdrawal from nicotine produces a greater increase in sweet food intake alongside general increases in chow intake. Changes in overall food intake in current and ex-smokers may lead to increased risk for obesity and other health problems, potentially limiting the benefit of quitting smoking. PMID- 26548503 TI - A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality. AB - Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0.81; 95 % CI 0.77, 0.85 for highest v. lowest quantile of intake, P het=0.04, I 2=43 %), CVD mortality (five studies; RR 0.73; 95 % CI 0.68, 0.78; P het=0.31, I 2=16 %), all CHD (three studies; RR 0.66; 95 % CI 0.48, 0.91; P het=0.0002, I 2=88 %) and CHD mortality (seven studies; RR 0.70; 95 % CI 0.64, 0.76; P het=0.65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0.71; 95 % CI 0.49, 1.03; P het=0.03, I 2=72 %) and stroke mortality (three studies; RR 0.83; 95 % CI 0.69, 1.00; P het=0.54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1.05; 95 % CI 0.69, 1.61; P het=0.04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death. PMID- 26548504 TI - Fiberoptic bronchoscopy findings in children with stridor in a tertiary hospital. PMID- 26548505 TI - Rhinitis: A clinical marker of COPD-asthma overlap phenotype? PMID- 26548506 TI - Cost Effectiveness of Outpatient Asthma Clinics. AB - INTRODUCTION: Asthma clinics (AC) are hospital outpatient services specialising in the management of asthma. In this study, we analysed the impact of these clinics on asthma management and their cost effectiveness in comparison with standard outpatient services. METHODS: A case cross-over study in which all new patients seen in the AC of Lugo in 2012 were included. The case period was defined as one year following the first visit to the AC; the control period was defined as the preceding year. We calculated changes in clinical quality indicators for asthma management, and estimated the incremental cost effectiveness ratio (ICER) for each additional patient treated and for each quality-adjusted life year (QALY) RESULTS: The number of patients (n=83, mean age 49 +/- 15.2 years; 60.2% women) managed in the AC increased from 41% to 86%. The Asthma Control Test score increased from 18.7 +/- 4.6 to 22.6 +/- 2.3 (p<0.05) and FEV1 increased from 81.4% +/- 17.5 to 84.4% +/- 16.6 (p<0.05). The number of exacerbations, hospitalisations and visits to accident and emergency fell by 75%. The number of patients given combination LABA+ICS therapy fell from 79.5% to 41%. The use of other drug therapy increased: anticholinergics, from 3.6% to 16.9%; ICS in monotherapy, from 3.6% to 45.8%; and omalizumab, from 0% to 6%. ICERs per patient managed and per QALY gained were ?1,399 and ?6,876, respectively (social perspective). CONCLUSIONS: Treatment in ACs is cost-effective and beneficial in asthma management. PMID- 26548507 TI - Risk factors for late recurrent candidaemia. A retrospective matched case-control study. AB - Incidence, risk factors and clinical significance of late recurrent (LR) candidaemia (>1 month between episodes) remains unclear. The 1219 episodes of candidaemia detected from January 1985 to December 2014 were reviewed. We selected all cases with more than one episode separated by at least 30 days after clinical resolution in the interim (cases) and compared each of them with two controls (patients with single episodes of candidaemia). Clinical strains were genotyped to differentiate relapses from re-infection. Eighteen patients (1.48%) had 36 episodes of LR candidaemia (median 4 months). Independent risk factors for recurrence in the multivariate analysis were: underlying gastrointestinal disease (OR 67.16; 95% CI 5.23-861.71; p 0.001) and fungaemia due to Candida parapsilosis (OR 9.10; 95% 1.33-62.00; p 0.02). All episodes of LR candidaemia diagnosed during the first 3 months were due to an intravascular source of infection, whereas in those occurring after 3 months the main source of the disease was the abdomen, followed by endocarditis, and urinary tract. Molecular typing showed that 42.9% of LR candidaemias were relapses and 57.1% were re-infections. Neither time of recurrence nor clinical origin could predict type of recurrence. LR candidaemia is a relatively rare event that is more frequent in patients who have an initial episode of candidaemia due to C. parapsilosis or an underlying gastrointestinal disease. Episodes of LR candidaemia that occur within the first 3 months should prompt an attempt to exclude an intravascular source of infection, whereas those occurring later point to an intra-abdominal origin. PMID- 26548508 TI - A comparison of telbivudine and entecavir in the treatment of hepatitis B e antigen-positive patients: a prospective cohort study in China. AB - There are few studies directly comparing the efficacy and safety of telbivudine and entecavir. The present prospective cohort study aimed to evaluate the long term efficacy and safety of these compounds in 196 hepatitis B e antigen (HBeAg) positive patients with chronic hepatitis B for a median follow-up period of 172 weeks; 97 were treated with telbivudine and 99 were treated with entecavir. Patients showing suboptimal responses could also take adefovir at 24-48 weeks and all patients with viral breakthrough were started on adefovir. The 240-week cumulative proportions of patients showing undetectable hepatitis B DNA levels and serum alanine transaminase (ALT) normalization were similar in the two study groups. Viral breakthrough developed in 14% of the telbivudine group and in 2% of the entecavir group (p 0.002). Interestingly, the cumulative proportions of patients treated with entecavir and telbivudine showing HBeAg seroconversion were 12% versus 21% at 48 weeks (p 0.041), 15% versus 38% at 96 weeks (p 0.001), 24% versus 50% at 144 weeks (p 0.001), 33% versus 53% at 192 weeks (p 0.004) and 36% versus 53% at 240 weeks (p 0.005), respectively. Patients treated with telbivudine were therefore significantly more likely to show HBeAg seroconversion than those receiving entecavir and similar results were observed in study sub groups matched for age, serum ALT, and HBV DNA levels. A safety analysis identified no differences between grade 3/4 creatine kinase elevations in the study groups and only telbivudine was associated with improved kidney function. PMID- 26548509 TI - Is real-time PCR-based diagnosis similar in performance to routine parasitological examination for the identification of Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica from stool samples? Evaluation of a new commercial multiplex PCR assay and literature review. AB - Microscopy is the reference standard for routine laboratory diagnosis in faecal parasitology but there is growing interest in alternative methods to overcome the limitations of microscopic examination, which is time-consuming and highly dependent on an operator's skills and expertise. Compared with microscopy, DNA detection by PCR is simple and can offer a better turnaround time. However, PCR performances remain difficult to assess as most studies have been conducted on a limited number of positive clinical samples and used in-house PCR methods. Our aim was to evaluate a new multiplex PCR assay (G-DiaParaTrio; Diagenode Diagnostics), targeting Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica. To minimize the turnaround time, PCR was coupled with automated DNA extraction (QiaSymphony; Qiagen). The PCR assay was evaluated using a reference panel of 185 samples established by routine microscopic examination using a standardized protocol including Ziehl-Neelsen staining and adhesin detection by ELISA (E. histolytica II; TechLab). This panel, collected from 12 French parasitology laboratories, included 135 positive samples for G. intestinalis (n = 38), C. parvum/C. hominis (n = 26), E. histolytica (n = 5), 21 other gastrointestinal parasites, together with 50 negative samples. In all, the G-DiaParaTrio multiplex PCR assay identified 38 G. intestinalis, 25 C. parvum/C. hominis and five E. histolytica leading to sensitivity/specificity of 92%/100%, 96%/100% and 100%/100% for G. intestinalis, C. parvum/C. hominis and E. histolytica, respectively. This new multiplex PCR assay offers fast and reliable results, similar to microscopy driven diagnosis for the detection of these gastrointestinal protozoa, allowing its implementation in routine clinical practice. PMID- 26548510 TI - Natural selection of K13 mutants of Plasmodium falciparum in response to artemisinin combination therapies in Thailand. AB - Resistance of Plasmodium falciparum to artemisinin combination therapy (ACT) in Southeast Asia can have a devastating impact on chemotherapy and control measures. In this study, the evolution of artemisinin-resistant P. falciparum in Thailand was assessed by exploring mutations in the K13 locus believed to confer drug resistance phenotype. P. falciparum-infected blood samples were obtained from patients in eight provinces of Thailand over two decades (1991-2014; n = 904). Analysis of the K13 gene was performed by either sequencing the complete coding region (n = 259) or mutation-specific PCR-restriction fragment length polymorphism method (n = 645). K13 mutations related to artesunate resistance were detected in isolates from Trat province bordering Cambodia in 1991, about 4 years preceding widespread deployment of ACT in Thailand and increased in frequency over time. Nonsynonymous nucleotide diversity exceeded synonymous nucleotide diversity in the propeller region of the K13 gene, supporting the hypothesis that this diversity was driven by natural selection. No single mutant appeared to be favoured in every population, and propeller-region mutants were rarely observed in linkage with each other in the same haplotype. On the other hand, there was a highly significant association between the occurrence of a propeller mutant and the insertion of two or three asparagines after residue 139 of K13. Whether this insertion plays a compensatory role for deleterious effects of propeller mutants on the function of the K13 protein requires further investigation. However, modification of duration of ACT from 2-day to 3-day regimens in 2008 throughout the country does not halt the increase in frequency of mutants conferring artemisinin resistance phenotype. PMID- 26548511 TI - Evidence of genotypic diversity among Candida auris isolates by multilocus sequence typing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and amplified fragment length polymorphism. AB - Candida auris is a multidrug-resistant nosocomial bloodstream pathogen that has been reported from Asian countries and South Africa. Herein, we studied the population structure and genetic relatedness among 104 global C. auris isolates from India, South Africa and Brazil using multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) fingerprinting and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RPB1, RPB2 and internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal DNA were sequenced for MLST. Further, genetic variation and proteomic assessment was carried out using AFLP and MALDI-TOF MS, respectively. Both MLST and AFLP typing clearly demarcated two major clusters comprising Indian and Brazilian isolates. However, the South African isolates were randomly distributed, suggesting different genotypes. MALDI-TOF MS spectral profiling also revealed evidence of geographical clustering but did not correlate fully with the genotyping methods. Notably, overall the population structure of C. auris showed evidence of geographical clustering by all the three techniques analysed. Antifungal susceptibility testing by the CLSI microbroth dilution method revealed that fluconazole had limited activity against 87% of isolates (MIC90, 64 mg/L). Also, MIC90 of AMB was 4 mg/L. Candida auris is emerging as an important yeast pathogen globally and requires reproducible laboratory methods for identification and typing. Evaluation of MALDI-TOF MS as a typing method for this yeast is warranted. PMID- 26548512 TI - Abnormal epigenetic regulation of the gene expression levels of Wnt2b and Wnt7b: Implications for neural tube defects. AB - The association between Wnt genes and neural tube defects (NTDs) is recognized, however, it remains to be fully elucidated. Our previous study demonstrated that epigenetic mechanisms are affected in human NTDs. Therefore, the present study aimed to evaluate whether Wnt2b and Wnt7b are susceptible to abnormal epigenetic modification in NTDs, using chromatin immunoprecipitation assays to evaluate histone enrichments and the MassARRAY platform to detect the methylation levels of target regions within Wnt genes. The results demonstrated that the transcriptional activities of Wnt2b and Wnt7b were abnormally upregulated in mouse fetuses with NTDs and, in the GC-rich promoters of these genes, histone 3 lysine 4 (H3K4) acetylation was enriched, whereas H3K27 trimethylation was reduced. Furthermore, several CpG sites in the altered histone modification of target regions were significantly hypomethylated. The present study also detected abnormal epigenetic modifications of these Wnt genes in human NTDs. In conclusion, the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure. These results improve understanding of the dysregulation of epigenetic modification of Wnt genes in NTDs. PMID- 26548513 TI - Reliability of radiographic measurements for acromioclavicular joint separations. AB - INTRODUCTION: The treatment of acromioclavicular (AC) joint separations is controversial, particularly for Rockwood type III injuries. Rockwood type IV injuries, which correspond to horizontal instability, are very likely under diagnosed. The objective of this study was to evaluate the inter- and intra observer reproducibility of the Rockwood classification through an evaluation of standard radiographs, as described in the original article. MATERIAL AND METHODS: This was a prospective radiographic study using protocol-based data from the 2014 symposium of the French Society of Arthroscopy (SFA). Fifteen anonymized radiological records were analysed by six independent examiners on two occasions, 1 week apart. The records consisted of a comparative A/P view of the two acromioclavicular joints (Zanca view), an axillary lateral view and dynamic lateral views (Tauber protocol) to uncover dynamic horizontal instability. A detailed analysis protocol was implemented that included absolute and relative measurements on each view; the relative measurements were used to account for radiographic magnification. RESULTS: The inter- and intra-observer reproducibility on the A/P radiographs was good to excellent. The reproducibility was fair to good on the lateral views, but the measurements varied greatly from one subject to another, and significant errors were found with certain records. The reproducibility of the dynamic views proposed by Tauber was poor to fair. DISCUSSION: Radiographic analysis of AC joint separations is reproducible in the vertical plane, which makes it possible to diagnose Rockwood type II, III and V injuries. On the other hand, static and dynamic analyses in the horizontal plane do not have good reproducibility and do not contribute to make an accurate diagnosis of Rockwood type IV injuries. LEVEL OF EVIDENCE: Level I, Diagnostic study. PMID- 26548514 TI - Fatal Takotsubo cardiomyopathy due to epinephrine in shoulder arthroscopy. AB - The authors report a case of a shoulder arthroscopy in which epinephrine saline irrigation was held responsible for acute hypertension followed by fatal Takotsubo cardiomyopathy. PMID- 26548515 TI - Technique to treat iliopsoas irritation after total hip replacement: Thickening of articular hip capsule through an abridged direct anterior approach. AB - Iliopsoas irritation due to acetabular cup component impingement following total hip arthroplasty (THA) is usually treated by infiltration or by distal iliopsoas tenotomy in case of recurrence; however, this can result in an active flexion deficit of the thigh. To prevent this complication, we developed an original technique that we performed between 2012 and 2014 in patients with recurrent impingement following extraarticular corticosteroid injections. This included 5 patients (mean age: 64 [53-75] years old) in whom we performed an ambulatory bursectomy by the Hueter approach and placed a polyglactin 910 (VicrylTM) mesh plate on the entire anterior hip capsule. After a mean follow-up of 12months (9 29months), anterior pain had decreased in all patients with improvement and an increase in the Oxford-12 (mean: 15 points [10-19]), Merle d'Aubigne (mean: 2.5 points [1-5]) and Harris (mean: 18 points [10-29]) scores. No flexion deficits were observed. An infected postoperative hematoma had to be drained but was cured at follow-up. This simple procedure provides satisfactory results and preserves THA function. It does not jeopardize future procedures and is an alternative option in case of unsuccessful conservative treatment. PMID- 26548516 TI - Perception and satisfaction with the information received during the medical care process in patients with prostate cancer. AB - OBJECTIVES: To assess the perception and degree of satisfaction of Spanish patients with prostate cancer (PC) concerning the information received during the medical care process. MATERIALS AND METHODS: We analysed information on the perception of the medical care process of 591 patients with PC who attended a consultation. We also studied their degree of participation in decision making and the association between perceived satisfaction and the demographic and clinical variables, both of patients and specialists. RESULTS: Some 90.2% of the patients stated that they had received, mainly from the urologist, an appropriate amount of information about the disease. More than 80% of the patients were satisfied with the information received at the time of diagnosis. Some 70.3% of the patients stated that they better accepted the disease thanks to the information provided, and 60.5% believed that they had a better ability to resolve problems. Some 90.4% of the patients considered that the time provided by the specialist was appropriate. Some 62.5% of the patients participated in making decisions about their disease and treatment. Age (both of the patient and specialist), the extent of the disease, the time dedicated by the specialist and the type of centre were factors that had a significant association (P<.05) with the satisfaction achieved. CONCLUSIONS: The perception and degree of satisfaction that Spanish patients with PC have of the information received during the medical care process is good and is paralleled by a high degree of active participation in the therapeutic decision making process. PMID- 26548518 TI - ? PMID- 26548517 TI - [Fixed pigmented erythema: Epidemiology, physiopathology, clinical features, differential diagnosis and therapeutic management]. PMID- 26548519 TI - [Intralesional corticosteroid injections for pre-sternal keloids]. PMID- 26548520 TI - [Lentigo maligna]. PMID- 26548521 TI - [Male median raphe]. PMID- 26548522 TI - Editorial. PMID- 26548523 TI - Protein-protein interactions of the LIM-only protein FHL2 and functional implication of the interactions relevant in cardiovascular disease. AB - FHL2 belongs to the LIM-domain only proteins and contains four and a half LIM domains, each of which are composed of two zinc finger structures. FHL2 exhibits specific interaction with proteins exhibiting diverse functions, including transmembrane receptors, transcription factors and transcription co-regulators, enzymes, and structural proteins. The function of these proteins is regulated by FHL2, which modulates intracellular signal transduction pathways involved in a plethora of cellular tasks. The present review summarizes the current knowledge on the protein interactome of FHL2 and provides an overview of the functional implication of these interactions in apoptosis, migration, and regulation of nuclear receptor function. FHL2 was originally identified in the heart and there is extensive literature available on the role of FHL2 in the cardiovascular system, which is also summarized in this review. PMID- 26548524 TI - Ultrasonic propagation in finite-length granular chains. AB - A narrowband ultrasound source has been used to generate solitary wave impulses in finite-length chains of spheres. Once the input signal is of sufficient amplitude, both harmonics and sub-harmonics of the input frequency can be generated as non-linear normal modes of the system, allowing a train of impulses to be established from a sinusoidal input. The characteristics of the response have been studied as a function of the physical properties of the chain, the input waveform and the level of static pre-compression. The results agree with the predictions of a theoretical model, based on a set of discrete dynamic equations for the spheres for finite-length chains. Impulses are only created for very small pre-compression forces of the order of 0.01N, where strongly non linear behaviour is expected. PMID- 26548525 TI - Guided torsional wave generation of a linear in-plane shear piezoelectric array in metallic pipes. AB - Cylindrical guided waves based techniques are effective and promising tools for damage detection in long pipes. The essential operations are generation and reception of guided waves in the structures utilizing transducers. A novel in plane shear (d36 type) PMNT wafer is proposed to generate and receive the guided wave, especially the torsional waves, in metallic pipes. In contrast to the traditional wafer, this wafer will directly introduce in-plane shear deformation when electrical field is conveniently applied through its thickness direction. A single square d36 PMNT wafer is bonded on the surface of the pipe positioned collinearly with its axis, when actuated can predominantly generate torsional (T) waves along the axial direction, circumferential shear horizontal (C-SH) waves along circumferential direction, and other complex cylindrical Lamb-like wave modes along other helical directions simultaneously. While a linear array of finite square size d36 PMNT wafers was equally spaced circumferentially, when actuated simultaneously can nearly uniform axisymmetric torsional waves generate in pipes and non-symmetric wave modes can be suppressed greatly if the number of the d36 PMNT wafer is sufficiently large. This paper first presents the working mechanism of the linear d36 PMNT array from finite element analysis (FEA) by examining the constructive and destructive displacement wavefield phenomena in metallic pipes. Furthermore, since the amplitude of the received fundamental torsional wave signal strongly depends on frequency, a series of experiments are conducted to determine the frequency tuning curve for the torsional wave mode. All results indicate the linear d36 PMNT array has potential for efficiently generating uniform torsional wavefield of the fundamental torsional wave mode, which is more effective in monitoring structural health in metallic pipes. PMID- 26548526 TI - In-line mixing states monitoring of suspensions using ultrasonic reflection technique. AB - Based on the measurement of echo signal changes caused by different concentration distributions in the mixing process, a simple ultrasonic reflection technique is proposed for in-line monitoring of the mixing states of suspensions in an agitated tank in this study. The relation between the echo signals and the concentration of suspensions is studied, and the mixing process of suspensions is tracked by in-line measurement of ultrasonic echo signals using two ultrasonic sensors. Through the analysis of echo signals over time, the mixing states of suspensions are obtained, and the homogeneity of suspensions is quantified. With the proposed technique, the effects of impeller diameter and agitation speed on the mixing process are studied, and the optimal agitation speed and the minimum mixing time to achieve the maximum homogeneity are acquired under different operating conditions and design parameters. The proposed technique is stable and feasible and shows great potential for in-line monitoring of mixing states of suspensions. PMID- 26548527 TI - Guided waves based diagnostic imaging of circumferential cracks in small-diameter pipe. AB - To improve the safety and reliability of pipeline structures, much work has been done using ultrasonic guided waves methods for pipe inspection. Though good for evaluating the defects in the pipes, most of the methods lack the capability to precisely identify the defects in the pipe features like welds or supports. Therefore, a novel guided wave based cross-sectional diagnostic imaging algorithm was developed to improve the ability of circumferential cracks identification in the pipe features. To ensure the accuracy of the imaging, an angular profile based frequency selection method is presented. As validation, the approach was employed to identify the presence and location of a small circumferential crack with 1.13% cross sectional area (CSA) in the welding zone of a 48 mm diameter type 304 stainless steel pipe. Accurate identification results have demonstrated the effectiveness of the developed approach. PMID- 26548528 TI - Cessation of facial growth in subjects with short, average, and long facial types - Implications for the timing of implant placement. AB - Placement of a single-tooth implant should be performed when a patient's facial growth has ceased. In this retrospective observational study, we evaluated if there was a difference in the timing of cessation of craniofacial growth in short, average, and long facial types. Based on the value of the angle between cranial base and mandibular plane (SN/MP angle), three groups comprising 48 subjects with short facial type (SF; SN/MP <=28 degrees ), 77 with average facial type (AF; SN/MP >=31.5 degrees and <=34.5 degrees ), and 44 with long facial type (LF; SN/MP >=38 degrees ) were selected. Facial growth was assessed on lateral cephalograms taken at 15.4 years of age, and 2, 5, and 10 years later. Variables were considered to be stable when the difference between two successive measurements was less than 1 mm or 1 degrees . We found no difference between facial types in the timing of cessation of facial growth. Depending on the variable, the mean age when variables became stable ranged from 18.0 years (Is Pal in LF group) to 22.0 years (SN/MP in LF group). However, facial growth continued at the last follow-up in approximately 20% subjects. This study demonstrates that facial type is not associated with the timing of cessation of facial growth. PMID- 26548529 TI - Endoscopic transnasal approach and intraoperative navigation for the treatment of isolated blowout fractures of the medial orbital wall. AB - The aim of this study is to describe the reduction of medial orbital wall fractures using a combination of two different techniques: the endoscopic reduction and the navigation aided reconstruction. The endoscopic approach avoids an external incision and allows the observation of the fracture site clearly. Navigation-aided reconstruction is essential to achieve precise and predictable results in orbital reconstruction. It consists in an ideal virtual reconstruction of the target area created using a mirroring tool, and superimposing and comparing the unaffected and the affected sides. This technique opens a broad spectrum of possible surgical approaches, especially in situations in which anatomical landmarks for precise positioning of bone fragments, or bone grafts, are missing. This study is the first to combine these two techniques. The study was carried out in seven patients who underwent endoscopic reduction of isolated blowout fractures of the medial orbital wall and navigation-aided reconstruction at the authors' institution. This pilot study clearly shows that a combination of the endoscopic reduction and the navigation-aided reconstruction provides functional results and great advantages in terms of anatomical preservation and postoperative morbidity. PMID- 26548530 TI - Dental MRI using a dedicated RF-coil at 3 Tesla. AB - PURPOSE: To assess the benefit of a dedicated surface coil to visualize dental structures in comparison to standard head/neck coil. METHODS: Measurements were performed using the standard head/neck coil and a dedicated array coil for dental MRI at 3 T. As MRI methods, we used a T1-weighted spin-echo sequence with and without spectral fat saturation, a T2-weighted turbo-spin-echo sequence and a 3 dimensional T2-weighted SPACE sequence. Measurements were performed in a phantom to examine sensitivity profiles. Then the signal gain in dental structures was examined in volunteers and in a patient. RESULTS: As expected for a surface coil, the signal gain of the dental coil was highest at the surface of the phantom and decreased with increasing distance to the coil; it was >120% even at a depth of 30 mm, measured from the centre of the coil. The signal gain within the pulp of the volunteers ranged between 236 and 413%. CONCLUSION: The dedicated array coil offers a significantly higher signal within the region of interest for dental MR imaging thus allowing for better depiction of pathologies within the periodontium and for delineation and tracking of the branches of the maxillary and mandibular nerves. PMID- 26548531 TI - Identification of microRNAs and microRNA targets in Xenopus gastrulae: The role of miR-26 in the regulation of Smad1. AB - MicroRNAs (miRNAs) are known to play diverse roles in the regulation of vertebrate development. To investigate miRNA-target mRNA relationships in embryonic development, we have carried out small-RNA sequencing to identify miRNAs expressed in the early gastrula of Xenopus laevis. We identify a total of 180 miRNAs, and we have identified the locations of the miRNA precursor sequences in the X. laevis genome. Of these miRNAs, 141 represent miRs previously identified in Xenopus tropicalis. Alignment to human miRNAs led to the identification of 39 miRNAs that have not previously been described for Xenopus. We have also used a biochemical approach to isolate mRNAs that are associated with the RNA-Induced Silencing Complex (RISC) in early gastrulae and thus candidate targets of miRNA-dependent regulation. Interrogation of this RISC associated mRNA pool by RT-PCR indicates that a number of genes essential for early patterning and specification may be under regulation by miRNAs. Smad1 transcripts are associated with the RISC; target prediction algorithms identify a single miRNA-binding site for miR-26, which is common to the 3'UTRs of Smad1a and Smad1b. Disruption of the interaction between miR-26 and the Smad1 3'UTR via a Target Protector Morpholino Oligonucleotide (TPMO) leads to a 2-fold increase in Smad1 protein accumulation, moderate increases in the expression of BMP4/Smad1 target genes, and a reduction in organizer gene expression, as well as a partially ventralized phenotype in approximately 25% of embryos. Overexpression of miR-26 resulted in moderately decreased expression of Smad1-dependent genes and an expansion of the region expressing the Organizer gene not1. Our findings indicate that interactions between miR-26 and the Smad1 3'UTR modulate Smad1 function in the establishment of axial patterning; they also establish a foundation for the functional analysis of miRNAs and their regulatory interactions during gastrulation. PMID- 26548532 TI - Expression of LMP and EBNA genes in Epstein-Barr virus-associated lymphomas in Hu PBL/SCID mice. AB - Transplantation of peripheral blood lymphocytes (PBLs) from healthy humans with latent Epstein-Barr virus (EBV) infection into severe combined immunodeficiency (SCID) mice results in development of EBV-associated human B-cell lymphoma. However, the expression of EBV genes in relation to lymphoma development has not been reported. We investigated latent membrane protein (LMP) and EBV nuclear antigen (EBNA) gene expression in PBLs from EBV-positive blood donors and induced lymphoma cells from SCID mice to elucidate the functions and effects of the EBV genome in the occurrence and development of lymphoma. PBLs were isolated from 9 healthy blood donors and transplanted into SCID mice. Gene expression levels of LMP-1, LMP-2A, and LMP-2B and EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C and EBNA LP were monitored by real-time quantitative-polymerase chain reaction (qRT-PCR) in cells from nine EBV-induced lymphomas and in matched lymphocytes from healthy subjects. LMP-1, EBNA-1 and EBNA-2 protein levels were detected by western blotting. As a result, LMP-1, LMP-2A and LMP-2B mRNA levels were upregulated 256 , 38- and 331-fold, respectively, in the EBV-induced lymphoma cells compared with the controls, while EBNA-1 and EBNA-3A mRNA levels were upregulated 1157- and 1154-fold, respectively. EBNA-2, EBNA-3B, EBNA-3C and EBNA-LP mRNAs were detected in lymphoma cells, but not in lymphocytes from EBV-positive blood donors. LMP-1 and EBNA-2 proteins were not expressed in lymphocytes from EBV-positive blood donors, according to western blotting. Weak EBNA-1 expression was observed in lymphocytes from blood donors with latent EBV infection, while LMP-1, EBNA-1 and EBNA-2 protein levels were significantly upregulated in EBV-induced lymphoma cells, consistent with mRNA expression levels detected by qRT-PCR. In conclusion, LMP-1, LMP-2A, LMP-2B, EBNA-1 and EBNA-3A were upregulated in EBV-induced lymphoma cells, while EBNA-2, EBNA-3B, EBNA-3C and EBNA-LP were absent in lymphocytes from humans with latent EBV infection, but were positively expressed in EBV-induced lymphoma cells. PMID- 26548535 TI - [Venous thromboembolic risk during repatriation for medical reasons]. AB - In France, approximately 3000 people are repatriated every year, either in a civil situation by insurers. Repatriation also concerns French army soldiers. The literature is scarce on the topic of venous thromboembolic risk and its prevention during repatriation for medical reasons, a common situation. Most studies have focused on the association between venous thrombosis and travel, a relationship recognized more than 60 years ago but still subject to debate. Examining the degree of venous thromboembolic risk during repatriation for medical reasons must take into account several parameters, related to the patient, to comorbid conditions and to repatriation modalities. Appropriate prevention must be determined on an individual basis. PMID- 26548534 TI - Cancer immunotherapy: Strategies for personalization and combinatorial approaches. AB - The results of recent clinical trials using novel immunotherapy strategies such as immune checkpoint blockade and adoptive T-cell therapy approaches including CAR T-cell therapy have clearly established immunotherapy as an important modality for the treatment of cancer besides the traditional approaches of surgery, radiotherapy, and chemotherapy or targeted therapy. However, to date immunotherapy has been shown to induce durable clinical benefit in only a fraction of the patients. The use of combination strategies is likely to increase the number of patients that might benefit from immunotherapy. Indeed, over the last decade, the characterization of multiple immune resistance mechanisms used by the tumor to evade the immune system and the development of agents that target those mechanisms has generated a lot of enthusiasm for cancer immunotherapy. But a critical issue is to determine how best to combine such agents. This review will focus on novel immunotherapy agents currently in development and discuss strategies to develop and personalize combination cancer immunotherapy strategies. PMID- 26548536 TI - [Necrotic leg ulcer revealing vasculitis induced by vitamin K antagonists]. AB - Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist. CASE REPORT: A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment. DISCUSSION: The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis. PMID- 26548537 TI - Life-Threatening Cardiac Tamponade Secondary to Chylopericardium Following Orthotopic Heart Transplantation-A Case Report. AB - Chylopericardium is a rare complication in cardiac surgery, and an extremely rare occurrence in patients following orthotopic heart transplantation (OHT), which, however, can lead to cardiac tamponade. Here we present a case of a 59-year-old man who underwent OHT and suffered from chylopericardium resulting in cardiac tamponade late in the postoperative course, despite the initially uneventful early postoperative period (decreasing blood drainage was observed directly after the procedure, and the drains were safely removed). After the diagnosis of chylopericardium was made, the conservative treatment was initiated, which turned out to be insufficient, and eventually invasive approach for the recurrence of tamponade secondary to chylopericardium was required. We discuss the available therapeutic options for chylopericardium and demonstrate the successful invasive therapeutic approach with use of the absorbable fibrin sealant patch. PMID- 26548533 TI - T-cell receptor gene therapy--ready to go viral? AB - T lymphocytes can be redirected to recognize a tumor target and harnessed to combat cancer by genetic introduction of T-cell receptors of a defined specificity. This approach has recently mediated encouraging clinical responses in patients with cancers previously regarded as incurable. However, despite the great promise, T-cell receptor gene therapy still faces a multitude of obstacles. Identification of epitopes that enable effective targeting of all the cells in a heterogeneous tumor while sparing normal tissues remains perhaps the most demanding challenge. Experience from clinical trials has revealed the dangers associated with T-cell receptor gene therapy and highlighted the need for reliable preclinical methods to identify potentially hazardous recognition of both intended and unintended epitopes in healthy tissues. Procedures for manufacturing large and highly potent T-cell populations can be optimized to enhance their antitumor efficacy. Here, we review the current knowledge gained from preclinical models and clinical trials using adoptive transfer of T-cell receptor-engineered T lymphocytes, discuss the major challenges involved and highlight potential strategies to increase the safety and efficacy to make T-cell receptor gene therapy a standard-of-care for large patient groups. PMID- 26548539 TI - Why should ethics approval be required prior to publication of health promotion research? AB - ISSUE ADDRESSED: Most academic journals that publish studies involving human participants require evidence that the research has been approved by a human research ethics committee (HREC). Yet journals continue to receive submissions from authors who have failed to obtain such approval. In this paper, we provide an ethical justification of why journals should not, in general, publish articles describing research that has no ethics approval, with particular attention to the health promotion context. METHODS: Using theoretical bioethical reasoning and drawing on a case study, we first rebut some potential criticisms of the need for research ethics approval. We then outline four positive claims to justify a presumption that research should, in most instances, be published only if it has been undertaken with HREC approval. RESULTS: We present four justifications for requiring ethics approval before publication: (1) HREC approval adds legitimacy to the research; (2) the process of obtaining HREC approval can improve the quality of an intervention being investigated; (3) obtaining HREC approval can help mitigate harm; and (4) obtaining HREC approval demonstrates respect for persons. CONCLUSION: This paper provides a systematic and comprehensive assessment of why research ethics approval should generally be obtained before publishing in the health promotion context. So what? Journals such as the Health Promotion Journal of Australia have recently begun to require research ethics approval for publishing research. Health promotion researchers will be interested in learning the ethical justification for this change. PMID- 26548538 TI - Arterial Vasoreactivity is Equally Affected by In Vivo Cross-Clamping with Increasing Loads in Young and Middle-Aged Mice Aortas. AB - PURPOSE: To compensate for the lack of haptic feedback by surgical robots, limitation of exerted forces could be implemented. The limits should be based on the observed relationship between tissue load and induced damage. This study examines whether age-related changes influence this relationship. METHODS: Descending thoracic aortas of male C57BL/6J mice of 10, 25 and 40 weeks were clamped in vivo (no clamp, 0.5N or 2.0N) for 2 min. Functional integrity was tested in vitro by studying endothelium-dependent and -independent vasoreactivity. RESULTS: Endothelium-dependent relaxation deteriorated with increased clamping force at all ages. Clamping did not influence endothelium independent vasodilation. Age (10, 25 and 40 weeks) did not significantly impact on the effect of clamping on endothelium-dependent and independent vasoreactivity. CONCLUSIONS: Within the tested conditions, mechanical clamping induces damage to the vascular endothelium, but not to the smooth muscle cells. Age has no effect on the obtained results in mice from 10 to 40 weeks old. PMID- 26548540 TI - Moving beyond evidence-based medicine: Incorporating patient values and preferences. PMID- 26548541 TI - Standards and guidelines for observational studies: quality is in the eye of the beholder. AB - OBJECTIVES: Patient care decisions demand high-quality research. To assist those decisions, numerous observational studies are being performed. Are the standards and guidelines to assess observational studies consistent and actionable? What policy considerations should be considered to ensure decision makers can determine if an observational study is of high-quality and valid to inform treatment decisions? STUDY DESIGN AND SETTING: Based on a literature review and input from six experts, we compared and contrasted nine standards/guidelines using 23 methodological elements involved in observational studies (e.g., study protocol, data analysis, and so forth). RESULTS: Fourteen elements (61%) were addressed by at least seven standards/guidelines; 12 of these elements disagreed in the approach. Nine elements (39%) were addressed by six or fewer standards/guidelines. Ten elements (43%) were not actionable in at least one standard/guideline that addressed the element. CONCLUSION: The lack of observational study standard/guideline agreement may contribute to variation in study conduct; disparities in what is considered credible research; and ultimately, what evidence is adopted. A common set of agreed on standards/guidelines for conducting observational studies will benefit funders, researchers, journal editors, and decision makers. PMID- 26548542 TI - A reduced factor structure for the PROQOL-HIV questionnaire provided reliable indicators of health-related quality of life. AB - OBJECTIVES: To identify a simplified factor structure for the PROQOL-human immunodeficiency virus (HIV) questionnaire to improve the measurement of the health-related quality of life (HRQL) of HIV-positive patients in clinical care and research settings. STUDY DESIGN AND SETTING: HRQL data were collected using the eight-dimension PROQOL-HIV questionnaire from 2,537 patients (VESPA2 study). Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) validated a simpler four-factor structure and assessed measurement invariance (MI). Multigroup analysis assessed the effect of sex, age, and antiretroviral therapy (ART) on the resulting factor scores. Correlations with symptom and Short Form (SF)-12 self-reports assessed convergent validity. RESULTS: Item analysis, EFA, and CFAs confirmed the validity [comparative fit index (CFI), 0.948; root mean square error of approximation, 0.064] and reliability (alpha's >= 0.8) of four dimensions: physical health and symptoms, health concerns and mental distress, social and intimate relationships, and treatment-related impact. Strong MI was demonstrated across sex and age (decrease in CFI <0.01). A multiple-cause multiple-indicator model indicated that HRQL correlated as expected with sex, age, and the ART status. Correlations of HRQL, symptom reports, and SF-12 scores evidenced convergent validity criterion. CONCLUSION: The simplified factor structure and scoring scheme for PROQOL-HIV will allow clinicians to monitor with greater reliability the HRQL of patients in clinical care and research settings. PMID- 26548543 TI - Caring for the Caregivers: Results of an Extended, Five-component Stress reduction Intervention for Hospital Staff. AB - The health-related consequences of stress in hospital workers and associated costs of absenteeism and high turnover have increased the need for programs targeting stress in this population. "Caring for the Caregivers," a multimodal approach to stress-reduction designed to address the multidimensional nature of stress in hospital staff, integrates five components: cognitive, somatic, dynamic, emotive and hands-on, in a flexible eight-month format. Significant improvements were demonstrated for 97 participants compared to 67 controls in pre post scores for the Maslach Burnout Inventory, Job-Related Tension Index, Perceived Stress Scale, Productivity Scale, General Health Questionnaire, Positive and Negative Affect Schedule, and Visual Analogue Scales of 12 stress associated symptoms. Together with significant reduction in upper respiratory infections and family doctor visits, these results suggest that providing hospital staff with multiple techniques addressing commonly encountered work stressors impacts positively on health and well-being and significantly reduces stress and burnout in this population. PMID- 26548544 TI - New pharmacological treatment options for irritable bowel syndrome with constipation. AB - INTRODUCTION: Constipation predominant irritable bowel syndrome (IBS-C) is a common disorder and accounts for a large number of ambulatory visits. Sensory abnormalities, that is, presence of abdominal pain and discomfort, distinguish IBS-C from chronic idiopathic constipation. AREA COVERED: This review focuses on the pharmacology, efficacy, safety, and future of prucalopride, YKP-10811, DSP 6952, dexloxiglumide, linaclotide, plecanatide, tenapanor, and elobixibat. EXPERT OPINION: It is now well established that treatment focusing only on bowel transit provides incomplete relief to patients with IBS-C. Improved understanding of pathophysiology of IBS-C has led to use of sensory end points like complete spontaneous bowel movements and the FDA combined end point (abdominal pain and complete spontaneous bowel movements) in clinical trials. A number of drugs are in development and provide hope for this challenging group of patients. However, because of recent failures secondary to ineffectiveness and/or adverse events, we cautiously await how clinical data play out in larger studies and in clinical practice. PMID- 26548545 TI - Serum levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT 3) in depressed patients with schizophrenia. AB - AIM: Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are neurotrophins-proteins that induce the survival, development, and function of neurons. Their role in the development of schizophrenia and mood disorders is widely studied. This study was aimed to determine whether depression affects levels of BDNF and NT-3 in patients with schizophrenia. METHODS: Data for 53 Caucasian adult hospitalized patients with chronic paranoid schizophrenia was compared with 27 healthy subjects. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and positive, negative and general sub-scores, the Calgary Depression Scale for Schizophrenia (CDSS), the Hamilton Depression Rating Scale (HDRS), and the Clinical Global Impressions scale (CGI). Patients were defined as depressed (SHZ-DEP) with scores CDSS > 6 and HDRS > 7, otherwise they were included into the non-depressed group (SHZ-nonDEP). RESULTS: In total, 17 patients (32.1%) with schizophrenia met criteria for depression. SHZ DEP patients had higher scores in HDRS, CDSS, PANSS total, PANSS negative, PANSS general and CGI (p < 0.001 for all comparisons). There were no differences in BDNF or NT-3 levels between patients with schizophrenia and controls. BDNF levels were lower in SHZ-DEP compared to SHZ-nonDEP: 18.82 +/- 5.95 versus 22.10 +/- 5.31 ng/mL, p = 0.045. NT-3 levels were higher in SHZ-DEP compared to SHZ-nonDEP: 133.31 +/- 222.19 versus 56.04 +/- 201.28 pg/mL, p = 0.033. CONCLUSION: There were no differences in neurotrophin levels between patients with schizophrenia and controls. We found lower BDNF and higher NT-3 serum levels in depressed patients with schizophrenia. PMID- 26548546 TI - Using 'big data' to validate claims made in the pharmaceutical approval process. AB - Big Data in the healthcare setting refers to the storage, assimilation, and analysis of large quantities of information regarding patient care. These data can be collected and stored in a wide variety of ways including electronic medical records collected at the patient bedside, or through medical records that are coded and passed to insurance companies for reimbursement. When these data are processed it is possible to validate claims as a part of the regulatory review process regarding the anticipated performance of medications and devices. In order to analyze properly claims by manufacturers and others, there is a need to express claims in terms that are testable in a timeframe that is useful and meaningful to formulary committees. Claims for the comparative benefits and costs, including budget impact, of products and devices need to be expressed in measurable terms, ideally in the context of submission or validation protocols. Claims should be either consistent with accessible Big Data or able to support observational studies where Big Data identifies target populations. Protocols should identify, in disaggregated terms, key variables that would lead to direct or proxy validation. Once these variables are identified, Big Data can be used to query massive quantities of data in the validation process. Research can be passive or active in nature. Passive, where the data are collected retrospectively; active where the researcher is prospectively looking for indicators of co-morbid conditions, side-effects or adverse events, testing these indicators to determine if claims are within desired ranges set forth by the manufacturer. Additionally, Big Data can be used to assess the effectiveness of therapy through health insurance records. This, for example, could indicate that disease or co-morbid conditions cease to be treated. Understanding the basic strengths and weaknesses of Big Data in the claim validation process provides a glimpse of the value that this research can provide to industry. Big Data can support a research agenda that focuses on the process of claims validation to support formulary submissions as well as inputs to ongoing disease area and therapeutic class reviews. PMID- 26548547 TI - Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study. AB - This study initially aimed to depict the molecular rationale evolving the role of lycopene in inhibiting the enzymatic activity of beta-hydroxy-beta-methylglutaryl CoA (HMG-CoA) reductase via in vitro and in silico analysis. Our results illustrated that lycopene exhibited strong HMG-CoA reductase inhibitory activity (IC50 value of 36 ng/ml) quite better than pravastatin (IC50 = 42 ng/ml) and strong DPPH free radical scavenging activity (IC50 value = 4.57 +/- 0.23 MUg/ml) as compared to ascorbic acid (IC50 value = 9.82 +/- 0.42 MUg/ml). Moreover, the Ki value of lycopene (36 ng/ml) depicted via Dixon plot was well concurred with an IC50 value of 36 +/- 1.8 ng/ml. Moreover, molecular informatics study showed that lycopene exhibited binding energy of -5.62 kcal/mol indicating high affinity for HMG-CoA reductase than HMG-CoA (DeltaG: -5.34 kcal/mol). Thus, in silico data clearly demonstrate and support the in vitro results that lycopene competitively inhibit HMG-CoA reductase activity by binding at the hydrophobic portion of HMG CoA reductase. PMID- 26548548 TI - The effect of flexible body armour on pulmonary function. AB - The additional mass and fit of current military in-service body armour (ISBA) can reduce pulmonary function in a way that is characteristic of a restrictive respiratory impairment. This could ultimately impair exercise capacity and military performance. This study compared pulmonary function (forced vital capacity [FVC] and forced expiratory volume in 1 s [FEV1]) in UK ISBA (15.3 kg) and three flexible body armours (BAs) (FA1: 10 kg; FA2: 7.8 kg; FA3: 10 kg) in eight male soldiers. The design of the ballistic plates differed between the BAs to improve the flexibility. FVC and FEV1 were reduced by 4-6%, without reduction in FEV1/FVC for ISBA, FA2 and FA3, when compared to NoBA (p < 0.05). No difference was observed between FA1 and NoBA. As expected, wearing BA caused a mild restrictive ventilatory impairment; however, modifications to BA design can reduce the degree of this impairment. Practitioner Summary: This study showed that wearing body armour caused a mild restrictive ventilatory impairment. However, the design of the armour can be modified to reduce the degree of this impairment. This may lead to improvements in soldier performance during tasks that require body armour. PMID- 26548550 TI - Prognostic and predictive biomarkers in prostate cancer. AB - Prostate cancer (PCa) is one of the leading causes of cancer death among males, especially in more developed countries. Diagnosis is often achieved at an early stage of the disease with prostate biopsy, following a screening test showing elevated serum levels of prostate-specific antigen or a positive digital rectal examination. Early detection of PCa has led to a substantial decline in the number of metastatic patients. However, the prostate-specific antigen screening test has proved to be a double-edged sword so far, as it also accounts for PCa overdiagnosis. Due to the variability of PCa features, accurate prognosis of PCa patients is very important for determining treatment options. Therefore, this review focuses on the most promising prognostic and predictive biomarkers in PCa, which are likely to play a pivotal role, alone or in panels, in the personalized medicine era that has recently emerged. PMID- 26548549 TI - Effect of savings-led economic empowerment on HIV preventive practices among orphaned adolescents in rural Uganda: results from the Suubi-Maka randomized experiment. AB - Improving economic resources of impoverished youth may alter intentions to engage in sexual risk behaviors by motivating positive future planning to avoid HIV risk and by altering economic contexts contributing to HIV risk. Yet, few studies have examined the effect of economic-strengthening on economic and sexual behaviors of orphaned youth, despite high poverty and high HIV infection in this population. Hierarchal longitudinal regressions were used to examine the effect of a savings led economic empowerment intervention, the Suubi-Maka Project, on changes in orphaned adolescents' cash savings and attitudes toward savings and HIV preventive practices over time. We randomized 346 Ugandan adolescents, aged 10-17 years, to either the control group receiving usual orphan care plus mentoring (n = 167) or the intervention group receiving usual orphan care plus mentoring, financial education, and matched savings accounts (n = 179). Assessments were conducted at baseline, 12, and 24 months. Results indicated that intervention adolescents significantly increased their cash savings over time (b = $US12.32, +/-1.12, p < .001) compared to adolescents in the control group. At 24 months post-baseline, 92% of intervention adolescents had accumulated savings compared to 43% in the control group (p < .001). The largest changes in savings goals were the proportion of intervention adolescents valuing saving for money to buy a home (DeltaT1-T0 = +14.9, p < .001), pursue vocational training (DeltaT1-T0 = +8.8, p < .01), and start a business (T1-T0 = +6.7, p < .01). Intervention adolescents also had a significant relative increase over time in HIV-preventive attitudinal scores (b = +0.19, +/-0.09, p < .05), most commonly toward perceived risk of HIV (95.8%, n = 159), sexual abstinence or postponement (91.6%, n = 152), and consistent condom use (93.4%, n = 144). In addition, intervention adolescents had 2.017 significantly greater odds of a maximum HIV-prevention score (OR = 2.017, 95%CI: 1.43-2.84). To minimize HIV risk throughout the adolescent and young adult periods, long-term strategies are needed to integrate youth economic development, including savings and income generation, with age-appropriate combination prevention interventions. PMID- 26548551 TI - 2D and 3D-QSAR analysis of pyrazole-thiazolinone derivatives as EGFR kinase inhibitors by CoMFA and CoMSIA. AB - Two and Three-dimensional quantitative structure-activity relationship (2D, 3D QSAR) study was performed for some pyrazole-thiazolinone derivatives as EGFR kinase inhibitors using the CoMFA, CoMSIA and GA-MLR methods. The utilized data set was split into training and test set based on hierarchical clustering technique. From the five CoMSIA descriptors, electrostatic field presented the highest correlation with the activity. The statistical parameters for the CoMFA (r(2)=0.862, q(2)=0.644) and CoMSIA (r(2)=0.851, q(2)=0.740) were obtained for the training set with the common substructure-based alignment. The obtained parameters indicated the superiority of the CoMSIA model over the CoMFA model. A test set consisted of seven compounds was used to evaluate the proposed models. The results of contour maps which were presented by each method lead to some insights for increasing the inhibition activity of compounds. The 2D-QSAR model was built based on three descriptors selected by genetic algorithm and showed high predictive ability (R(2) train= 0.843, Q(2) LOO=0.787). Molecular docking study was also performed to understand the type interactions presented in binding site of the receptor and ligand. The developed models in parallel with molecular docking can be employed to design and derive novel compounds with the potent EGFR inhibitory activity. PMID- 26548552 TI - Interaction Studies of Withania Somnifera's Key Metabolite Withaferin A with Different Receptors Assoociated with Cardiovascular Disease. AB - Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, beta1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease. PMID- 26548553 TI - 'No one was there to care for us': Ashodaya Samithi's community-led care and support for people living with HIV in Mysore, India. AB - Under the umbrella of the Bill and Melinda Gates-funded HIV initiative in India, the Mysore-based sex workers' (SWs) collective Ashodaya Samithi focused on improving its members' living and working conditions through community-led structural interventions, including community mobilisation, advocacy, peer-led support, and health promotional activities. Based on four months of ethnographic fieldwork, this article examines the care and support activities of one of its sub-wings, Ashraya, which specifically focuses on people living with HIV and AIDS (PLHIV). We first discuss the stigma-related perceptions and experiences of participants in relation to health-care settings and work environment, families and communities, and within varied HIV support networks. We then explore how Ashraya's community-led interventions attempt to challenge the structural forces feeding on and creating stigma. We argue that the current policy focus on the involvement of SWs' collectives in sexually transmitted infection (STI) prevention in India is rather limited and should be expanded along the continuum of care and support offered to PLHIV. As suggested in this paper, SWs' organisations may have greater potential to contribute to more than STI prevention work, both within and outside their communities, than currently recognised. PMID- 26548554 TI - Choice of excipients for gelly-like pulp prepared ex tempore "on a spoon"- "placebo" and with sartans. AB - CONTEXT: To ensure safe oral administration, pediatric patients require an appropriate dosage form to be swallowed without relevant difficulties. Ex tempore hydrated powders, forming viscous pulp "on a spoon", have recently gained much interest as pediatric formulations. The aim of this study was to evaluate the viscosity-increasing substances and disintegrants, alone or in mixtures, as excipients suitable for preparing such formulations, with candesartan and valsartan chosen as model active substances. METHODS: The mixtures of excipients were prepared in the form of powders, granules or lyophilizates, which were evaluated in terms of their ability to form a homogenous mass after hydration with a small amount of water. The best compositions were tested with candesartan cilexetil and valsartan (2% and 10% w/w, respectively). Performed studies include macroscopic, organoleptic and microscopic observations, as well as a textural analysis, determination of gelation time and rheological measurements. RESULTS: Mixtures of guar gum, lactose and one of the disintegrants (F-Melt M, Prosolv 50, Prosolv Easy, Lycatab, Pharmaburst, Pearlitol) demonstrated the best properties. With regard to drug-incorporating formulations, granules were evaluated as the most satisfying form, while the functional properties of lyophilized formulations were poor. CONCLUSION: Granules with candesartan cilexetil (2%) were found to be the most promising for further development. PMID- 26548555 TI - Youth Development as Subjectified Subjectivity - a Dialectical-Ecological Model of Analysis. AB - The aim of this article is to shed light on how environmental standards in the life of youths influence the development of self. We propose the concept of 'subjectified subjectivity' to grasp these person-environment dialectics in a general form. By elaborating on these conceptual understandings of youth life, the article also seeks to understand young people from their own perspectives on life and from their developing life-perspectives, rather than from general categories. Based on one of the author's data from her study of young people in their transition to (and through the first year of) high school, we carry out an analysis of a 16-year old high school student and how her approach to beer, to beer drinking as a part of Danish high school life-style, and to herself changes over time. We suggest a dialectical-ecological model to analyze the dialectical and synthetic movements over time of the girl and her environments. PMID- 26548556 TI - Radio frequency measurements of tunnel couplings and singlet-triplet spin states in Si:P quantum dots. AB - Spin states of the electrons and nuclei of phosphorus donors in silicon are strong candidates for quantum information processing applications given their excellent coherence times. Designing a scalable donor-based quantum computer will require both knowledge of the relationship between device geometry and electron tunnel couplings, and a spin readout strategy that uses minimal physical space in the device. Here we use radio frequency reflectometry to measure singlet-triplet states of a few-donor Si:P double quantum dot and demonstrate that the exchange energy can be tuned by at least two orders of magnitude, from 20 MUeV to 8 meV. We measure dot-lead tunnel rates by analysis of the reflected signal and show that they change from 100 MHz to 22 GHz as the number of electrons on a quantum dot is increased from 1 to 4. These techniques present an approach for characterizing, operating and engineering scalable qubit devices based on donors in silicon. PMID- 26548557 TI - The impacts of Wolbachia and the microbiome on mate choice in Drosophila melanogaster. AB - Symbionts and parasites can manipulate their hosts' reproduction to their own benefit, profoundly influencing patterns of mate choice and evolution of the host population. Wolbachia is one of the most widespread symbionts among arthropods, and one that alters its hosts' reproduction in diverse and dramatic ways. While we are beginning to appreciate how Wolbachia's extreme manipulations of host reproduction can influence species diversification and reproductive isolation, we understand little about how symbionts and Wolbachia, in particular, may affect intrapopulation processes of mate choice. We hypothesized that the maternally transmitted Wolbachia would increase the attractiveness of its female hosts to further its own spread. We therefore tested the effects of Wolbachia removal and microbiome disruption on female attractiveness and male mate choice among ten isofemale lines of Drosophila melanogaster. We found variable effects of general microbiome disruption on female attractiveness, with indications that bacteria interact with hosts in a line-specific manner to affect female attractiveness. However, we found no evidence that Wolbachia influence female attractiveness or male mate choice among these lines. Although the endosymbiont Wolbachia can greatly alter the reproduction of their hosts in many species, there is no indication that they alter mate choice behaviours in D. melanogaster. PMID- 26548558 TI - Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism. AB - The solute carrier 27A (SLC27A) gene family encodes fatty acid transport proteins (FATPs) and includes 6 members. During fetal and postnatal periods of development, the growing brain requires a reliable supply of fatty acids. Because autism spectrum disorders (ASD) are now recognized as disorders caused by impaired early brain development, it is possible that functional abnormalities of SLC27A genes may contribute to the pathogenesis of ASD. Here, we confirmed the expression of SLC27A3 and SLC27A4 in human neural stem cells derived from human induced pluripotent stem cells, which suggested their involvement in the developmental stage of the central nervous system. Additionally, we resequenced the SLC27A3 and SLC27A4 genes using 267 ASD patient and 1140 control samples and detected 47 (44 novel and 29 nonsynonymous) and 30 (17 novel and 14 nonsynonymous) variants for the SLC27A3 and SLC27A4, respectively, revealing that they are highly polymorphic with multiple rare variants. The SLC27A4 Ser209 allele was more frequently represented in ASD samples. Furthermore, we showed that a SLC27A4 Ser209 mutant resulted in significantly higher fluorescently labeled fatty acid uptake into bEnd3 cells, a mouse brain capillary-derived endothelial cell line, compared with SLC27A4 Gly209, suggesting that the functional change may contribute to ASD pathophysiology. PMID- 26548560 TI - PP242 suppresses bladder cancer cell proliferation and migration through deactivating the mammalian target of rapamycin complex 2/AKT1 signaling pathway. AB - While most cancer types are resistant to mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, recent studies have identified mTORC2 as an important prospective therapeutic target for cancer. The present study assessed the effects of mTORC2 inhibitor PP242 on the proliferation and migration of bladder cancer cells by using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays. Furthermore, the phosphorylation status of downstream signaling proteins of mTORC1 and mTORC2 was assessed using western blot analysis. The results demonstrated that PP242 concentration-dependently inhibited the proliferation of bladder cancer cells. Simultaneously, the migration ability of bladder cancer cells was suppressed by PP242. In addition, PP242 markedly restrained the phosphorylation of AKT1 and mTORC2, while the phosphorylation status of S6K1 and mTORC1 was not affected. These results suggested that PP242 exerts potent inhibitory effects on bladder cancer cells by modulating the activity of the mTORC2/AKT1 pathway. PMID- 26548559 TI - Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation. AB - Efficiency of cell-based tissue engineering and regenerative medicine has been limited by inadequate cellular responses to injury because of aging and poor controllability of cellular interactions. Since cell progression is under a tight epigenetic regulation, epigenetic modulators such as 5-azacytidine (5-Aza-CR) have been utilized to facilitate reprogramming and development of somatic cells in 2-dimensional (2-D) settings. Nonetheless, progression of a specific tissue lineage toward the terminal phenotype is dependent not only on the genomic potential, but also on the microenvironment cues that are beyond the capability of 2-D approaches. In this study, we investigated the combined effects of matrices of variable rigidities and the treatment with the epigenetic modulator 5 Aza-CR on reprogramming adipose-derived stromal cells (ADSCs) into myoblast-like cells by utilizing tunable transglutaminase cross-linked gelatin (Col-Tgel) in vitro and in vivo. Our experiments demonstrated that cellular plasticity and trans-differentiation were significantly enhanced when ADSCs were treated with an effective dose of 5-Aza-CR (1.25 to 12.5 ng) in the optimal myogenic matrix (15 +/- 5 kPa Col-Tgel). Our findings suggest that both physical signals and chemical milieu are critical for the regulation of cellular responses. PMID- 26548561 TI - Nipple Malposition following Nipple-Sparing Mastectomy. How Can We Prevent It? PMID- 26548562 TI - Inappropriate Shock Due to T-Wave Oversensing by a Subcutaneous ICD after Alcohol Septal Ablation for Hypertrophic Cardiomyopathy. AB - A 53-year-old female patient with hypertrophic obstructive cardiomyopathy (HOCM) was admitted for alcohol septal ablation (ASA). A subcutaneous internal cardioverter defibrillator (S-ICD) was implanted for primary prevention. After ASA, the patient developed a right bundle branch block, and the S-ICD delivered a total of five inappropriate shocks due to T-wave oversensing (TWOS). TWOS is a relatively frequent cause of inappropriate shocks in S-ICD patients. After invasive treatment for HOCM, there is a risk of developing intraventricular conduction delay and subsequent changes in QRS and T-wave morphology. This should be taken into consideration when ICD indication is evaluated in HOCM patients. PMID- 26548564 TI - Bats and Rodents Shape Mammalian Retroviral Phylogeny. AB - Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID- 26548563 TI - Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons. AB - BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. PMID- 26548565 TI - Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs. AB - 1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients. PMID- 26548566 TI - Tears of wine: new insights on an old phenomenon. AB - Anyone who has enjoyed a glass of wine has undoubtedly noticed the regular pattern of liquid beads that fall along the inside of the glass, or 'tears of wine.' The phenomenon is the result of a flow against gravity along the liquid film on the glass, which is induced by an interfacial tension gradient. It is generally accepted that the interfacial tension gradient is due to a composition gradient resulting from the evaporation of ethanol. We re-examine the tears of wine phenomenon and investigate the importance of thermal effects, which previously have been ignored. Using a novel experiment and simple model we find that evaporative cooling contributes significantly to the flow responsible for wine tears, and that this phenomenon occurs primarily because of the thermodynamic behavior of ethanol-water mixtures. Also, the regular pattern of tear formation is identified as a well-known hydrodynamic instability. PMID- 26548567 TI - Spectroscopic characterization of charge carrier anisotropic motion in twisted few-layer graphene. AB - Graphene, a layer of carbon atoms in a honeycomb lattice, captures enormous interest as probably the most promising component of future electronics thanks to its mechanical robustness, flexibility, and unique charge carrier quasiparticles propagating like massless high energy Dirac fermions. If several graphene layers form a stack, the interaction between them is, on the one hand, weak, allowing realization of various registries between the layers and, on the other hand, strong enough for a wide range tuning of the electronic properties. Here we grow few layer graphene with various number of layers and twist configurations and address the electronic properties of individual atomic layers in single microscopic domains using angle-resolved photoelectron spectromicroscopy. The dependence of the interlayer coupling on the twist angle is analyzed and, in the domains with tri-layers and more, if different rotations are present, the electrons in weaker coupled adjacent layers are shown to have different properties manifested by coexisting van Hove singularities, moire superlattices with corresponding superlattice Dirac points, and charge carrier group velocity renormalizations. Moreover, pronounced anisotropy in the charge carrier motion, opening a possibility to transform strongly coupled graphene bilayers into quasi one-dimensional conductors, is observed. PMID- 26548568 TI - 1,8-Naphthyridine Derivatives: A Review of Multiple Biological Activities. AB - The 1,8-naphthyridine group of compounds have gained special attention of researchers on account of their demonstrating a variety of interesting biological activities. A wide range of biological properties establishes them as potent scaffolds in therapeutic and medicinal research. The broad spectrum of activities primarily includes antimicrobial, antiviral, anticancer, anti-inflammatory, and analgesic activities. 1,8-Naphthyridine derivatives have also exhibited potential applications in neurological disorders such as Alzheimer's disease, multiple sclerosis, and depression. In addition, these synthetic derivatives have been found to possess activities such as anti-osteoporotic (alpha(v)beta(3) antagonists), anti-allergic, antimalarial, gastric antisecretory, bronchodilator, anticonvulsant, anti-hypertensive, platelet aggregation inhibition, anti-oxidant, EGFR inhibition, protein kinase inhibition, ionotropic agent, beta-3 antagonist, MDR modulator, adenosine receptor agonist, adrenoceptor antagonist, and pesticide activities. In spite of the widespread application of the 1,8-naphythyridine scaffolds, only a limited number of review articles are available till date. In this review, we attempt to compile and discuss the key data available in the literature for the multiple biological activities of 1,8-naphthyridine derivatives, in a chronological manner. This review compilation (with 199 references) may be helpful in understanding the diverse biological properties of 1,8-naphthyridines and provide insights into their mechanism of action. This may direct future research in the synthesis of new derivatives and exploring this scaffold for other possible biological activities. PMID- 26548569 TI - Effect of Molecular Coupling on Ultrafast Electron-Transfer and Charge Recombination Dynamics in a Wide-Gap ZnS Nanoaggregate Sensitized by Triphenyl Methane Dyes. AB - Wide-band-gap ZnS nanocrystals (NCs) were synthesized, and after sensitizing the NCs with series of triphenyl methane (TPM) dyes, ultrafast charge-transfer dynamics was demonstrated. HRTEM images of ZnS NCs show the formation of aggregate crystals with a flower-like structure. Exciton absorption and lumimescence, due to quantum confinement of the ZnS NCs, appear at approximately 310 and 340 nm, respectively. Interestingly, all the TPM dyes (pyrogallol red, bromopyrogallol red, and aurin tricarboxylic acid) form charge-transfer complexes with the ZnS NCs, with the appearance of a red-shifted band. Electron injection from the photoexcited TPM dyes into the conduction band of the ZnS NCs is shown to be a thermodynamically viable process, as confirmed by steady-state and time resolved emission studies. To unravel charge-transfer (both electron injection and charge recombination) dynamics and the effect of molecular coupling, femtosecond transient absorption studies were carried out in TPM-sensitized ZnS NCs. The electron-injection dynamics is pulse-width-limited in all the ZnS/TPM dye systems, however, the back electron transfer differs, depending on the molecular coupling of the sensitizers (TPM dyes). The detailed mechanisms for the above-mentioned processes are discussed. PMID- 26548570 TI - Quantitative MS analysis of therapeutic mAbs and their glycosylation for pharmacokinetics study. AB - Therapeutic mAbs play an important role in the treatment of a wide range of diseases. Due to their complexity, comprehensive evaluation of their pharmacokinetics has yet to be fully achieved. It is crucial to develop sensitive, accurate, reliable, and reproducible methods for quantitation of mAbs in complex samples. In addition, it is also important to evaluate the PTMs which can affect their safety and/or effectiveness. MS-based methods provide an emerging approach for quantitation of proteins and their modification forms. In this review, we give a brief overview of quantification analysis of mAbs in complex biological samples and the characterization of N-glycosylation by biological MS. PMID- 26548571 TI - Epistemic Trust and Education: Effects of Informant Reliability on Student Learning of Decimal Concepts. AB - The epistemic trust literature emphasizes that children's evaluations of informants' trustworthiness affects learning, but there is no evidence that epistemic trust affects learning in academic domains. The current study investigated how reliability affects decimal learning. Fourth and fifth graders (N = 122; Mage = 10.1 years) compared examples from consistently accurate and inaccurate informants (consistent) or informants who were each sometimes accurate and inaccurate (inconsistent). Fourth graders had higher conceptual knowledge and fewer misconceptions in the consistent condition than the inconsistent condition, and vice versa for fifth graders due to differences in prior exposure to decimals. Given the same examples, learning differed depending on informant reliability. Thus, epistemic trust is a malleable factor that affects learning in an academic domain. PMID- 26548573 TI - The neurodynamics of emotion: delineating typical and atypical emotional processes during adolescence. AB - The study of development is, in and of itself, the study of change over time, but emotions, particularly emotional reactivity and emotional regulation, also unfold over time, albeit over briefer time-scales. Adolescence is a period of development characterized by marked changes in emotional processes and rewiring of the underlying neural circuitry, making this time of life formative. Yet this period is also a time of increased risk for anxiety and mood disorders. Changes in the temporal dynamics of emotional processes (e.g. magnitude, time-to-peak and duration) occur during this developmental period and have been associated with risk for mood and anxiety disorders. In this article, we describe how the temporal dynamics of emotions change during adolescence and how they may increase risk for these psychopathologies. We highlight studies that illustrate how formalizing temporal neurodynamics of emotion may enhance links among levels of analyses from neurobiological to real-world, moment-to-moment experiences. PMID- 26548572 TI - The chemopreventive activity of butyrate-containing structured lipids in experimental rat hepatocarcinogenesis. AB - SCOPE: Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of tributyrin and flaxseed oil on rat hepatocarcinogenesis. METHODS AND RESULTS: Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with STLs, tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than tributyrin on oncogene expression. CONCLUSION: These results demonstrate that the tumor suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats. PMID- 26548574 TI - From soft to hard magnetic Fe-Co-B by spontaneous strain: a combined first principles and thin film study. AB - In order to convert the well-known Fe-Co-B alloy from a soft to a hard magnet, we propose tetragonal strain by interstitial boron. Density functional theory reveals that when B atoms occupy octahedral interstitial sites, the bcc Fe-Co lattice is strained spontaneously. Such highly distorted Fe-Co is predicted to reach a strong magnetocrystalline anisotropy which may compete with shape anisotropy. To probe this theoretical suggestion experimentally, epitaxial films are examined. A spontaneous strain up to 5% lattice distortion is obtained for B content up to 4 at%, which leads to uniaxial anisotropy constants exceeding 0.5 MJ m(-3). However, a further addition of B results in a partial amorphisation, which degrades both anisotropy and magnetisation. PMID- 26548575 TI - A Combined NMR and Computational Approach to Determine the RGDechi-hCit-alphav beta3 Integrin Recognition Mode in Isolated Cell Membranes. AB - The critical role of integrins in tumor progression and metastasis has stimulated intense efforts to identify pharmacological agents that can modulate integrin function. In recent years, alphav beta3 and alphav beta5 integrin antagonists were demonstrated to be effective in blocking tumor progression. RGDechi-hCit, a chimeric peptide containing a cyclic RGD motif linked to an echistatin C-terminal fragment, is able to recognize selectively alphav beta3 integrin both in vitro and in vivo. High-resolution molecular details of the selective alphav beta3 recognition of the peptide are certainly required, nonetheless RGDechi-hCit internalization limited the use of classical in cell NMR experiments. To overcome such limitations, we used WM266 isolated cellular membranes to accomplish a detailed NMR interaction study that, combined with a computational analysis, provides significant structural insights into alphav beta3 molecular recognition by RGDechi-hCit. Remarkably, on the basis of the identified molecular determinants, we design a RGDechi-hCit mutant that is selective for alphav beta5 integrin. PMID- 26548576 TI - Endothelium-dependent hyperpolarization: age, gender and blood pressure, do they matter? AB - Under physiological conditions, the endothelium generates vasodilator signals [prostacyclin, nitric oxide NO and endothelium-dependent hyperpolarization (EDH)], for the regulation of vascular tone. The relative importance of these two signals depends on the diameter of the blood vessels: as the diameter of the arteries decreases, the contribution of EDH to the regulation of vascular tone increases. The mechanism involved in EDH varies with species and blood vessel types; nevertheless, activation of endothelial intermediate- and small conductance calcium-activated potassium channels (IKCa and SKCa , respectively) is characteristic of the EDH pathway. IKCa - and SKCa -mediated EDH are reduced with endothelial dysfunction, which develops with ageing and hypertension, and is less pronounced in female than in age-matched male until after menopause. Impaired EDH-mediated relaxation is related to a reduced involvement of SKCa , so that the response becomes more dependent on IKCa . The latter depends on the activation of adenosine monophosphate-activated protein kinase (AMPK) and silent information regulator T1 (SIRT1), proteins associated with the process of cellular senescence and vascular signalling in response to the female hormone. An understanding of the role of AMPK and/or SIRT1 in EDH-like responses may help identifying effective pharmacological strategies to prevent the development of vascular complications of different aetiologies. PMID- 26548577 TI - Discovering of Tumor-targeting Peptides using Bi-functional Microarray. AB - A bi-functional microarray for in situ peptide screening is presented herein, from which an affinity peptide towards EpCAM is screened out for tumor cell capture. PMID- 26548578 TI - Combination of Hedgehog inhibitors and standard anticancer agents synergistically prevent osteosarcoma growth. AB - High-dose chemotherapy and surgical intervention have improved long-term prognosis for non-metastatic osteosarcoma to 50-80%. However, metastatic osteosarcoma exhibits resistance to standard chemotherapy. We and others have investigated the function of Hedgehog pathway in osteosarcoma. To apply our previous findings in clinical settings, we examined the effects of Hedgehog inhibitors including arsenic trioxide (ATO) and vismodegib combined with standard anticancer agents. We performed WST-1 assays using ATO, cisplatin (CDDP), ifosfamide (IFO), doxorubicin (DOX), and vismodegib. Combination-index (CI) was used to examine synergism using CalcuSyn software. Xenograft models were used to examine the synergism in vivo. WST-1 assays showed that 143B and Saos2 cell proliferation was inhibited by ATO combined with CDDP, IFO, DOX, and vismodegib. Combination of ATO and CDDP, IFO, DOX or vismodegib was synergistic when the two compounds were used on proliferating 143B and Saos2 human osteosarcoma cells. An osteosarcoma xenograft model showed that treatment with ATO and CDDP, IFO, or vismodegib significantly prevented osteosarcoma growth in vivo compared with vehicle treatment. Our findings indicate that combination of Hedgehog pathway inhibitors and standard FDA-approved anticancer agents with established safety for human use may be an attractive therapeutic method for treating osteosarcoma. PMID- 26548580 TI - Analysis of pelvic rotation on the standard hip ventrodorsal extended radiographic view. AB - OBJECTIVES: To study the symmetry of the iliac horizontal diameter (IHD) maximum obturator foramen width (OFW), ischiatic femoral overlap (IFO), pelvic horizontal radius (PHR), femoral head diameter (FHD), and obturator foramen area (OFA) parameters in the normal hip extended radiographic view and to evaluate the correlation of pelvic rotation with the magnitude of asymmetry of these parameters. METHODS: Nine canine cadavers from adult, large and giant breeds were radiographed in standard hip extended views and with 2 degrees , 4 degrees and 6 degrees degrees of rotation. The variables IHD, OFW, IFO, PHR, FHD, and OFA were analysed in radiographs. RESULTS: The IHD measurements exhibited repeatability, bilateral symmetry and 95% of confidence interval of asymmetry in different pelvic rotations without superposition (p <0.05); OFW and IFO exhibited repeatability, bilateral symmetry and a small superposition in 95% of confidence interval of asymmetry according different pelvic rotations; PHR, FHD and OFA exhibited repeatability, bilateral symmetry and unacceptable superposition in 95% of confidence interval of asymmetry depending on pelvic rotation. CLINICAL SIGNIFICANCE: The IHD is the recommended variable and OFW is an acceptable variable in order to evaluate slight pelvic rotation. The data may be used in qualitative analyses of hip extended radiographic views. In the future, complementary studies should be performed to evaluate the impact of degree of pelvic rotation on the hip dysplasia score. PMID- 26548581 TI - Magnetism in olivine-type LiCo(1-x)Fe(x)PO4 cathode materials: bridging theory and experiment. AB - In the current paper, we present a non-aqueous sol-gel synthesis of olivine type LiCo1-xFexPO4 compounds (x = 0.00, 0.25, 0.50, 0.75, 1.00). The magnetic properties of the olivines are measured experimentally and calculated using first principles theory. Specifically, the electronic and magnetic properties are studied in detail with standard density functional theory (DFT), as well as by including spin-orbit coupling (SOC), which couples the spin to the crystal structure. We find that the Co(2+) ions exhibit strong orbital moment in the pure LiCoPO4 system, which is partially quenched upon substitution of Co(2+) by Fe(2+). Interestingly, we also observe a non-negligible orbital moment on the Fe(2+) ion. We underscore that the inclusion of SOC in the calculations is essential to obtain qualitative agreement with the observed effective magnetic moments. Additionally, Wannier functions were used to understand the experimentally observed rising trend in the Neel temperature, which is directly related to the magnetic exchange interaction paths in the materials. We suggest that out of layer M-O-P-O-M magnetic interactions (J?) are present in the studied materials. The current findings shed light on important differences observed in the electrochemistry of the cathode material LiCoPO4 compared to the already mature olivine material LiFePO4. PMID- 26548582 TI - Readily prepared inclusion forming chiral calixsalens. AB - Calixsalens, chiral triangular hexaimines are readily synthesized by [3 + 3] cyclocondensation of trans-(R,R)-1,2-diaminocyclohexane with 2 hydroxyisophthalaldehyde derivatives. The usually rigid calixsalen ring is able to invert its conformation as a consequence of steric repulsion between bulky substituents at the C5 positions of the aromatic rings. The steric and electronic nature of the substituents does not affect only the conformation of the macrocycle. Small polar substituents enforce dimeric self-association to form an apohost where each of the monomers simultaneously serves as the host and the guest of its partner. Non-associating calixsalens form assemblies in which two symmetry-related molecules are arranged in a head-to-head fashion to form a capsule, or unimolecular cages that are able to entrap solvent molecules in their intrinsic voids. PMID- 26548583 TI - Activation of molecular oxygen by a molybdenum complex for catalytic oxidation. AB - A sterically demanding molybdenum(VI) dioxo complex was found to catalytically activate molecular oxygen and to transfer its oxygen atoms to phosphines. Intermediate peroxo as well as reduced mono-oxo complexes were isolated and fully characterized. Monomeric Mo(IV) monooxo species proved to be of an unusual nature with the coordinated phosphine trans to the oxo group. The reduced molybdenum centers can activate O2 to form a stable Mo(VI) oxo-peroxo complex unambiguously characterized by single crystal X-ray diffraction analysis. NMR experiments demonstrate that both oxygen atoms of the peroxo unit are transferred to an accepting substrate, generating the Mo(IV) intermediate and restarting the catalytic cycle. PMID- 26548584 TI - Real-time imaging of cancer cell chemotaxis in paper-based scaffolds. AB - Cellular migration is the movement of cells, cultured as a monolayer; cellular invasion is similar to migration, but requires the cells to move through a three dimensional material such as basement membrane extract or a synthetic hydrogel. Migration assays, such as the transwell assay, are widely used to study cellular movement because they are amenable to high-throughput screens with minimal experimental setup. These assays offer limited information about cellular responses to gradients in vivo because they oversimplify the threedimensional (3D) environment of a tissue. There are a number of invasion assays that support 3D cultures, some of which provide experimental control over the spatial and temporal gradients imparted on the culture. These assays, in their current form, are difficult to setup and maintain, and often require specialized laboratory equipment or engineering expertise. Here we describe a paper-based invasion assay in which cellular movement can be monitored in real-time with fluorescence microscopy. These assays are easily prepared and utilize materials commonly found in any laboratory: a single sheet of paper. These sheets are wax patterned to contain channels in which cells suspended in a hydrogel are seeded and cultured. Cell-containing sheets of paper are placed in a custom-built holder that allows gradients to form along the length of the channels. In this work, we compare the invasion of cells cultured in the presence and absence of an oxygen gradient. Our result support previous findings that oxygen is a chemoattractant, and selectively directs cellular movement in a 3D culture environment. PMID- 26548585 TI - Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States. AB - We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PI-containing as opposed to NNRTI containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long term health implications of abnormal acylcarnitine metabolism at birth in HEU children. PMID- 26548586 TI - New Antiglycative Compounds from Cumin (Cuminum cyminum) Spice. AB - Cumin (Cuminum cyminum L.), a widely consumed food spice, has been reported to have antiglycative effects in vitro and in vivo, but there is a paucity of data on its bioactive compounds. Herein, we report the isolation and structure elucidation (by NMR, HRESIMS, and CD) of 21 (1-21) compounds from a methanol extract of cumin seeds. The isolates included five new compounds: two sesquiterpenoids, two pairs of monoterpeneoid epimers, and a chalcone, named cuminoids A-E, respectively. The isolates were evaluated for antiglycative effects using the bovine serum albumin-fructose intrinsic fluorescence assay. At equivalent concentrations, several of the isolates, including cuminoids C-E, were more potent inhibitors than the positive control, aminoguanidine, a synthetic antiglycative agent (>50 vs 35%, respectively). PMID- 26548587 TI - Enzyme encapsulation in zeolitic imidazolate frameworks: a comparison between controlled co-precipitation and biomimetic mineralisation. AB - Recent studies have demonstrated that metal-organic frameworks can be employed as protective coatings for enzymes. Two efficient strategies have been reported for the synthesis of such composite materials: biomimetic mineralisation and controlled co-precipitation using polyvinylpyrrolidone. We assessed the relative efficacy of each approach by comparing the thermal stability of encapsulated urease. The resulting data shows that over a range of temperatures biomimetic mineralisation offers superior protection than the co-precipitation method. PMID- 26548588 TI - Two-Photon Lithography of 3D Nanocomposite Piezoelectric Scaffolds for Cell Stimulation. AB - In this letter, we report on the fabrication, the characterization, and the in vitro testing of structures suitable for cell culturing, prepared through two photon polymerization of a nanocomposite resist. More in details, commercially available Ormocomp has been doped with piezoelectric barium titanate nanoparticles, and bioinspired 3D structures resembling trabeculae of sponge bone have been fabricated. After an extensive characterization, preliminary in vitro testing demonstrated that both the topographical and the piezoelectric cues of these scaffolds are able to enhance the differentiation process of human SaOS-2 cells. PMID- 26548589 TI - Sol-Gel-Based Titania-Silica Thin Film Overlay for Long Period Fiber Grating Based Biosensors. AB - An evanescent wave optical fiber biosensor based on titania-silica-coated long period grating (LPG) is presented. The chemical overlay, which increases the refractive index (RI) sensitivity of the sensor, consists of a sol-gel-based titania-silica thin film, deposited along the sensing portion of the fiber by means of the dip-coating technique. Changing both the sol viscosity and the withdrawal speed during the dip-coating made it possible to adjust the thickness of the film overlay, which is a crucial parameter for the sensor performance. After the functionalization of the fiber surface using a methacrylic acid/methacrylate copolymer, an antibody/antigen (IgG/anti-IgG) assay was carried out to assess the performance of sol-gel based titania-silica-coated LPGs as biosensors. The analyte concentration was determined from the wavelength shift at the end of the binding process and from the initial binding rate. This is the first time that a sol-gel based titania-silica-coated LPG is proposed as an effective and feasible label-free biosensor. The specificity of the sensor was validated by performing the same model assay after spiking anti-IgG into human serum. With this structured LPG, detection limits of the order of tens of micrograms per liter (10(-11) M) are attained. PMID- 26548590 TI - Association of Pre-Operative Albuminuria with Post-Operative Outcomes after Coronary Artery Bypass Grafting. AB - The effect on post-operative outcomes after coronary artery bypass graft (CABG) surgery is not clear. Among 17,812 patients who underwent CABG during October 1,2006-September 28,2012 in any Department of US Veterans Affairs (VA) hospital, we identified 5,968 with available preoperative urine albumin-creatinine ratio (UACR) measurements. We examined the association of UACR<30, 30-299 and >=300 mg/g with 30/90/180/365-day and overall all-cause mortality, and hospitalization length >10 days, and with acute kidney injury(AKI). Mean +/- SD baseline age and eGFR were 66 +/- 8 years and 77 +/- 19 ml/min/1.73 m(2), respectively. 788 patients (13.2%) died during a median follow-up of 3.2 years, and 26.8% patients developed AKI (23.1%-Stage 1; 2.9%-Stage 2; 0.8%-Stage 3) within 30 days of CABG. The median lengths of stay were 8 days (IQR: 6-13 days), 10 days (IQR: 7-14 days) and 12 days (IQR: 8-19 days) for groups with UACR < 30 mg/g, 30-299 mg/g and >=300 mg/g, respectively. Higher UACR conferred 72 to 85% higher 90-, 180-, and 365-day mortality compared to UACR<30 mg/g (odds ratio and 95% confidence interval for UACR>=300 vs. <30 mg/g: 1.72(1.01-2.95); 1.85(1.14-3.01); 1.74(1.15 2.61), respectively). Higher UACR was also associated with significantly longer hospitalizations and higher incidence of all stages of AKI. Higher UACR is associated with significantly higher odds of mortality, longer post-CABG hospitalization, and higher AKI incidence. PMID- 26548591 TI - An RNA Molecule Derived From Sendai Virus DI Particles Induces Antitumor Immunity and Cancer Cell-selective Apoptosis. AB - Inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) induces anticancer immunity and cancer cell-selective apoptosis through the recognition of viral RNA genome fragments by retinoic acid-inducible gene-I (RIG I). Here, we discovered that the "copy-back" type of defective-interfering (DI) particles that exist in the Cantell strain of HVJ induced the human PC3 prostate cancer cell death more effectively than the Sendai/52 strain or Cantell strain, which contain fewer DI particles. DI particle genomic RNA (~550 bases) activated proapoptotic genes such as Noxa and/or TNF-related apoptosis-inducing ligand (TRAIL) in human prostate cancer cells to induce cancer cell-selective apoptosis. DI particle-derived RNA was synthesized by in vitro transcription (in vitro transcribed (IVT)-B2). IVT-B2 RNA, which has a double-stranded region in its secondary structure, promoted a stronger anticancer effect than IVT-HN RNA, which does not have a double-stranded region in its secondary structure. The intratumoral transfection of IVT-B2 significantly reduced the volume of a human prostate tumor and induced tumor cell apoptosis in the xenograft mouse model. Moreover, the involvement of natural killer (NK) cells in IVT-B2-RNA-induced anticancer effects was also suggested. These findings provide a novel nucleic acid medicine for the treatment of cancer. PMID- 26548592 TI - Choline Kinase Beta-Related Muscular Dystrophy, Appearance of Muscle Involvement on Magnetic Resonance Imaging. AB - BACKGROUND: Clinical presentation with motor delay, proximal weakness, and learning difficulties raise the possibility of a dystrophinopathy, dystroglycanopathy, or myotonic dystrophy. This differential should also include the more recently described choline kinase beta-related muscular dystrophy. This condition is typically characterized by large and abnormally distributed mitochondria on muscle biopsy, which can distinguish this condition from the other muscle conditions in the differential. METHODS: We present a boy with choline kinase beta mutations with relatively mild clinical manifestations, including proximal weakness, learning difficulties and elevated creatine kinase. Investigations included muscle magnetic resonance imaging (MRI) with T1 axial sequences through thigh and calves, and needle muscle biopsy of the left vastus lateralis muscle. RESULTS: MRI showed involvement mainly of the quadriceps femoris, sartorius, and adductor magnus, with selective sparing of the gracilis, hamstrings, and adductor longus and brevis. Muscle biopsy revealed chronic dystrophic features. Oxidative stains demonstrated enlarged mitochondria accentuated peripherally or present diffusely in a few fibres giving a coarsely stippled appearance. A homozygous C.722A>G (p.Asn241Ser) mutation was detected in exon 6 of the CHKB gene. CONCLUSION: This selective pattern of skeletal muscle involvement might be helpful for identifying other patients with this condition, even in the absence of diagnostic muscle pathology. PMID- 26548593 TI - Intraventricular Cyst Causing Acute Obstructive Hydrocephalus: Neurocysticercosis Managed With Neuroendoscopy. PMID- 26548594 TI - Epidemiological analysis of pneumococcal serotype 19A in healthy children following PCV7 vaccination. AB - After the introduction of conjugate vaccines, a strong rearrangement of pneumococcal serotypes was observed globally. Probably most concerning was the emergence of serotype 19A, which has not only high invasive disease potential, but also high antibiotic resistance. In the current study we focused on the increased prevalence of serotype 19A after the PCV vaccination rate became widely used in Hungary. A total of 2262 children aged 3-6 years were screened for pneumococcus carriage using nasal swabs. Children were divided into two groups according to the vaccination rates, low level (group 1) vs. high level (group 2). While the carriage rate did not change over time (average 32.9%), the serotype distribution differed greatly in the two groups. The prevalence of serotype 19A increased >eightfold. Almost all 19A isolates had high-level macrolide resistance and elevated penicillin minimum inhibitory concentrations. Genotyping methods revealed that these new 19A isolates are different from the previously frequent Hungary19A-6 PMEN clone. Both the carriage rate and the overall penicillin and macrolide resistance remained stable over time, but while several serotypes were represented in group 1, serotype 19A alone was clearly dominant in group 2. PMID- 26548595 TI - Alkylphloroglucinol derivatives and triterpenoids with soluble epoxide hydrolase inhibitory activity from Callistemon citrinus. AB - Phytochemical analysis of the leaves and stems of Callistemon citrinus (Curtis) Skeels led to the isolation of two new alkylphloroglucinols, gallomyrtucommulone E and F (1 and 2), along with four other known alkylphloroglucinol derivatives, gallomyrtucommulone A (3), endoperoxide G3 (4), myrtucommulone B (5), callistenone B (6) and five known triterpenoids, including betulinic acid (7), 3beta-acetylmorolic acid (8), 3beta-hydroxy-urs-11-en-13(28)-olide (9), diospyrolide (10) and ursolic acid (11). The structures of the natural compounds were determined from the spectroscopic evidences including 1D-/2D-NMR and HR-MS spectrometry. All the isolated compounds were assessed for the effects on the sEH inhibitory activity. The acylphloroglucinols myrtucommulone B (5)/callistenone B (6) (in mixture), and two triterpenoids, ursolic acid (11) and 3beta-hydroxy-urs 11-en-13(28)-olide (9) displayed strong inhibition of sEH activity, with IC50 values of 0.7, 11.2 and 24.8 MUM, respectively. PMID- 26548596 TI - Editorial. PMID- 26548597 TI - Polyunsaturated fat intake and mortality in non-statin users: Is there an independent relationship? PMID- 26548599 TI - Irregularity of energy intake at meals: prospective associations with the metabolic syndrome in adults of the 1946 British birth cohort. AB - Irregularity in eating patterns could be a potential cardiometabolic risk factor. We aimed to study the associations of irregular intake of energy at meals in relation to cardiometabolic risk factors 10 and 17 years later. Variability of energy intake data - derived from 5-d estimated diet diaries of cohort members of the National Survey for Health and Development collected at ages 36 (n 1416), 43 (n 1505) and 53 years (n 1381) - was used as a measure for irregularity. Associations between meal irregularity scores with cardiometabolic risk factors measured 10 and 17 years later were investigated using linear mixed models and logistic regression models. The results showed that irregularity scores changed significantly over the years (P<0.05). At age 36 years, subjects with a more irregular intake of energy at lunch (OR 1.42; 95 % CI 1.05, 1.91) and between meals (OR 1.35; 95 % CI 1.01, 1.82) had an increased risk for the metabolic syndrome 17 years later; at lunch was also associated with an increased waist circumference (OR 1.58; 95 % 1.27, 1.96) and TAG levels (OR 1.33; 95 % CI 1.02, 1.72). At age 43 years, subjects with a more irregular intake at breakfast had an increased risk of the metabolic syndrome 10 years later (OR 1.53; 95 % CI 1.15, 2.04), as well as an increased BMI (OR 1.66; 95 % CI 1.31, 2.10), waist circumference (OR 1.53; 95 % CI 1.23, 1.90) and diastolic blood pressure (OR 1.42; 95 % CI 1.13, 1.78). In conclusion, subjects with a more irregular intake of energy, mostly at breakfast and lunch, appeared to have an increased cardiometabolic risk 10 and 17 years later. PMID- 26548598 TI - PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway. AB - PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100MUM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100MUg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50MUM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha expression, and increased adipogenesis. This study points to a potential role of PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health. PMID- 26548600 TI - Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy. AB - BACKGROUND AND PURPOSE: Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. MATERIALS AND METHODS: A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. RESULTS: A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. CONCLUSION: Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment. PMID- 26548601 TI - [Management and clinical outcome in patients over 80 years with rectal cancer treated between 2006 and 2008 in Southern France (PACA region)]. AB - PURPOSE: Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. PATIENTS AND METHODS: Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Cote-d'Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse free-survival were correlated with patients' characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. RESULTS: With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0-T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse free survival of 95.2%. For T3-T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy. CONCLUSION: Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients. PMID- 26548602 TI - [MALT lymphoma of the prostate: Place of radiotherapy. Case report and discussion]. AB - We report the case of a patient presenting with MALT (mucosa-associated lymphoid tissue) lymphoma of the prostate, who received an irradiation delivering 30.6 Gy in 17 fractions after transurethral resection. With a follow-up of 6 years, he remained alive and free of disease. In view of the literature and this case report, definitive local irradiation should be administered in this rare disease. PMID- 26548603 TI - Non-linear contribution of serum vitamin D to symptomatic diabetic neuropathy: A case-control study. AB - AIMS: Vitamin D deficiency has recently been speculated to be associated with increased risk of diabetes neuropathy (DN). The aim of this study was to evaluate the odds of symptomatic DN across serum vitamin D levels. METHODS: All patients with DM were assessed using diabetic neuropathy symptoms and diabetic neuropathy examination score. Overall, 150 cases with DN and 600 controls were included. Serum 25-hydroxyvitamin D (25-OH-D) was measured to determine vitamin D status. RESULTS: A non-linear association between 25-OH-D and suffering from symptomatic DN was observed which was extracted after stratifying the ORs across different serum 25-OH-D levels. When compared to individuals with 25-OH-D of 30-40 ng/mL, patients with deficient (<20 ng/mL) vitamin D levels had higher odds of having symptomatic DN (OR: 2.04, 95%CI: 0.99-4.02, P=0.054). Participants with vitamin D values of greater than 40 ng/mL were also more likely to exhibit symptomatic DN (fully adjusted OR: 4.29, 95%CI: 1.59-11.55). CONCLUSIONS: We hypothesize a non linear contribution of serum vitamin D to symptomatic DN occurrence, which emphasizes that administration of vitamin D should be monitored and evaluated more carefully, especially in patients with diabetes. PMID- 26548605 TI - Control of Klebsiella pneumoniae pulmonary infection and immunomodulation by oral treatment with the commensal probiotic Bifidobacterium longum 5(1A). AB - Klebsiella pneumoniae (Kp) a common cause of pneumonia leads to intense lung injury and mortality that are correlated with infective exacerbations. Probiotics are a class of microorganisms that have immunomodulatory effects to benefit health. We investigated whether the probiotic Bifidobacterium longum 5(1A) induces protection in mice against lung infection induced by Kp and the potential involved mechanisms. Kp infection induced secretion of pro-inflammatory cytokines, neutrophil recruitment, significant bacterial load in the lung and 50% lethality. However, treatment with live B. longum 5(1A) induced faster resolution of inflammation associated with an increased production of IL-10, decreased lung damage with significantly reduction of bacterial burden that contributed to rescue 100% of mice from death. We found that these effects could be attributed, at least in part, to activation of the Toll-like receptor (TLR) adapter protein Mal, since B. longum 5(1A) treatment in Mal-deficient infected mice did not show the protection observed in wild type infected mice. Thus, we propose that live B. longum 5(1A) activates TLR-signaling pathway that results in ROS production and protects the host against pneumonia-induced death by finely tuning the inflammatory response and contributing to faster return to lung homeostasis. PMID- 26548604 TI - Metabolic Syndrome Among Marijuana Users in the United States: An Analysis of National Health and Nutrition Examination Survey Data. AB - BACKGROUND: Research on the health effects of marijuana use in light of its increased medical use and the current obesity epidemic is needed. Our objective was to explore the relationship between marijuana use and metabolic syndrome across stages of adulthood. METHODS: An analysis of 20- to 59-year-olds (n = 8478) who completed the 2005-2010 National Health and Nutrition Examination Surveys was conducted. Marijuana use was categorized as: never used, past use (used previously but not within the last 30 days), and current use (>=1 day in the last 30 days). Metabolic syndrome was defined as >=3 of the following: elevated fasting glucose, high triglycerides, low high-density-lipoprotein cholesterol, elevated systolic/diastolic blood pressure, and increased waist circumference. An age-stratified analysis was conducted to examine the relationship between marijuana use and metabolic syndrome among emerging adults (20-30 years), adults (31-44 years), and middle-aged adults (45-59 years). RESULTS: Fourteen percent (13.8%) of current marijuana users and 17.5% of past marijuana users presented with metabolic syndrome, compared with 19.5% of never users (P = .0003 and P = .03, respectively). Current marijuana users had lower odds of presenting with metabolic syndrome than never users (adjusted odds ratio [AOR] 0.69; 95% confidence interval [CI], 0.47-1.00; P = .05). Among emerging adults, current marijuana users were 54% less likely than never users to present with metabolic syndrome. Current (AOR 0.49; 95% CI, 0.25-0.97) and past (AOR 0.61; 95% CI, 0.40-0.91) middle-aged adult marijuana users were less likely to have metabolic syndrome than never users. CONCLUSIONS: Current marijuana use is associated with lower odds of metabolic syndrome across emerging and middle-aged US adults. Future studies should examine the biological pathways of this relationship. PMID- 26548606 TI - Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1. AB - Defensins, RNases and cytokines are present at mucosal barriers, main ports of HIV entry, and are potential mediators of the resistant phenotype exhibited by HIV-1-exposed seronegative individuals (HESN) during sexual exposure. We aimed to determine the role of soluble factors in natural resistance to HIV-1 infection. Vaginal/endocervical/oral mucosal samples were taken from 60 HESN, 60 seropositive (SP) and 61 healthy controls (HC). Human neutrophil peptide 1 (hNP 1), human beta defensin (hBD) 2 and 3, RNases, MIP-1beta and RANTES mRNA transcripts were quantified by qPCR and in vitro single-round, recombinant-based viral infectivity assay was used to evaluate the anti-HIV-1 activity of hBDs and RNases. HESN expressed significantly higher levels of hNP-1, hBDs mRNA in oral mucosa compared to HC (P < 0.05). In genital mucosa, significantly higher mRNA levels of MIP-1beta, RANTES and RNases were found in HESN compared to HC (P < 0.05). HBDs and RNases inhibit HIV-1 replication, particularly R5 at entry, reverse transcription and nuclear import of the viral life cycle. hNP-1, hBDs, MIP-1beta, RANTES and RNases, collectively could contribute to HIV-1 resistance during sexual exposure. Moreover, the inhibition of HIV-1 infection in vitro by hBDs and RNases suggests that they may be exploited as potential antiretrovirals. PMID- 26548607 TI - UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner. AB - Ubiquitin-like with plant homeodomain (PHD) and RING-finger domain 1 (UHRF1) maintains methylation patterns following DNA replication and is expressed at high levels in various types of human cancer. UHRF1 has been identified as a novel oncogene involved in the pathogenesis of hepatocellular carcinoma. Previous studies have demonstrated that inhibition of the expression of UHRF1 suppresses the proliferation of cancer cells. However, the role of UHRF1 in human osteosarcoma has not been investigated. The present study examined the expression levels of UHRF1 and retinoblastoma 1 (Rb1) in human osteosarcoma cell lines by western blot analysis. Stable overexpression of UHRF1 or knockdown of Rb1 was achieved by lentiviral transfection. Subsequently, a Cell Counting Kit-8 assay and a cell invasion assay were performed to detect the biological functions of UHRF1 in vitro. The results of the present study demonstrated that UHRF1 promoted the proliferation of human osteosarcoma cells. The present study also reported that UHRF1 was able to enhance the invasion of osteosarcoma cells in a retinoblastoma 1 (Rb1)-dependent manner. UHRF1 promoted invasion in Rb1-positive osteosarcoma cells, but not in Saos-2 cells with homozygous loss of Rb1. Similarly, knockdown of Rb1 in Rb1-positive osteosarcoma cells enhanced levels of invasion and eliminated the regulation of invasion by UHRF1. UHRF1 was found to inhibit the mRNA and protein expression levels of Rb1. Furthermore, deletion of Rb1 was found to suppress the expression of E-cadherin and promote epithelial-to mesenchymal transition (EMT). In addition, the overexpression of UHRF1 inhibited the expression of E-cadherin and promoted EMT via the suppression of Rb1. These data demonstrated that UHRF1 promotes osteosarcoma cell invasion by downregulating the expression of E-cadherin and increasing EMT in an Rb1 dependent manner. PMID- 26548608 TI - Assessing the abundance, seasonal questing activity, and Borrelia and tick-borne encephalitis virus (TBEV) prevalence of Ixodes ricinus ticks in a Lyme borreliosis endemic area in Southwest Finland. AB - Studies have revealed that Ixodes ricinus (Acari: Ixodidae) have become more abundant and their geographical distribution extended northwards in some Nordic countries during the past few decades. However, ecological data of tick populations in Finland are sparse. In the current study, I. ricinus abundance, seasonal questing activity, and their Borrelia spp. and tick-borne encephalitis virus (TBEV) prevalence were evaluated in a Lyme borreliosis endemic area in Southwest Finland, Seili Island, where a previous study mapping tick densities was conducted 12 years earlier. A total of 1940 ticks were collected from five different biotopes by cloth dragging during May-September 2012. The overall tick density observed was 5.2 ticks/100m(2) for nymphs and adults. Seasonal questing activity of ticks differed between biotopes and life stages: bimodal occurrences were observed especially for nymphal and adult ticks in forested biotopes, while larvae in pastures exhibited mostly unimodal occurrence. Prevalence of Borrelia and TBEV in ticks was evaluated using conventional and real-time PCR. All samples were negative for TBEV. Borrelia prevalence was 25.0% for adults (n=44) and the minimum infection rate (MIR) 5.6% for pooled nymph samples (191 samples, 1-14 individuals per sample; 30/191 positive). No Borrelia were detected in pooled larval samples (63 samples, 1-139 individuals per sample). Five species of Borrelia were identified from the samples: B. afzelii, B. burgdorferi s.s., B. garinii, B. valaisiana and B. miyamotoi. In Finland, B. valaisiana and B. miyamotoi have previously been reported from the Aland Islands but not from the mainland or inner archipelago. The results of the present study suggest an increase in I. ricinus abundance on the island. PMID- 26548609 TI - Siberian subtype tick-borne encephalitis virus in Ixodes ricinus in a newly emerged focus, Finland. AB - The first tick-borne encephalitis (TBE) cases in Kotka, Finland appeared in 2010. Altogether ten human cases have been diagnosed by 2014. Four had long-lasting sequelae. We collected 195 Ixodes ricinus ticks, nine rodents, and eleven shrews from the archipelago of Kotka in 2011. Three Siberian subtype TBE virus (TBEV) strains were isolated from the ticks and three mammals were positive for TBEV antibodies. The archipelago of Kotka is a newly emerged TBE focus of Siberian subtype TBEV circulating notably in I. ricinus. The patients had on average longer hospitalization than reported for the European subtype infection. PMID- 26548610 TI - Visualization of Compartmentalized Kinase Activity Dynamics Using Adaptable BimKARs. AB - The ability to monitor kinase activity dynamics in live cells greatly aids the study of how signaling events are spatiotemporally regulated. Here, we report on the adaptability of bimolecular kinase activity reporters (bimKARs) as molecular tools to enhance the real-time visualization of kinase activity. We demonstrate that the bimKAR design is truly versatile and can be used to monitor a variety of kinases, including JNK, ERK, and AMPK. Furthermore, bimKARs can have significantly enhanced dynamic ranges over their unimolecular counterparts, allowing the elucidation of previously undetectable kinase activity dynamics. Using these newly designed bimKARs, we investigate the regulation of AMPK by protein kinase A (PKA) in the plasma membrane, and demonstrate that PKA can both negatively and positively regulate AMPK activity in the same cell. PMID- 26548611 TI - Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers. AB - Suppression of RAD52 causes synthetic lethality in BRCA-deficient cells. Yet pharmacological inhibition of RAD52, which binds single-strand DNA (ssDNA) and lacks enzymatic activity, has not been demonstrated. Here, we identify the small molecule 6-hydroxy-DL-dopa (6-OH-dopa) as a major allosteric inhibitor of the RAD52 ssDNA binding domain. For example, we find that multiple small molecules bind to and completely transform RAD52 undecamer rings into dimers, which abolishes the ssDNA binding channel observed in crystal structures. 6-OH-Dopa also disrupts RAD52 heptamer and undecamer ring superstructures, and suppresses RAD52 recruitment and recombination activity in cells with negligible effects on other double-strand break repair pathways. Importantly, we show that 6-OH-dopa selectively inhibits the proliferation of BRCA-deficient cancer cells, including those obtained from leukemia patients. Taken together, these data demonstrate small-molecule disruption of RAD52 rings as a promising mechanism for precision medicine in BRCA-deficient cancers. PMID- 26548612 TI - Bioorthogonal Labeling of Ghrelin Receptor to Facilitate Studies of Ligand Dependent Conformational Dynamics. AB - Ghrelin receptor (GhrR) is a promising drug target because of its central role in energy homeostasis. GhrR, known for high constitutive activity, is thought to display multi-state conformations during activation and signaling. We used genetically encoded unnatural amino acids and bioorthogonal labeling reactions to engineer multiple fluorescent donor-acceptor pairs to probe ligand-directed structural changes in GhrR. We demonstrate how conformational dynamics of a G protein-coupled receptor can be measured in reconstituted systems. PMID- 26548614 TI - Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities that Lead to Inhibition of the Therapeutic Target IL-13. AB - The practical realization of disease modulation by catalytic degradation of a therapeutic target protein suffers from the difficulty to identify candidate proteases, or to engineer their specificity. We identified 23 measurable, specific, and new protease activities using combinatorial screening of 27 human proteases against 24 therapeutic protein targets. We investigate the cleavage of monocyte chemoattractant protein 1, interleukin-6 (IL-6), and IL-13 by matrix metalloproteinases (MMPs) and serine proteases, and demonstrate that cleavage of IL-13 leads to potent inhibition of its biological activity in vitro. MMP-8 degraded human IL-13 most efficiently in vitro and ex vivo in human IL-13 transgenic mouse bronchoalveolar lavage. Hence, MMP-8 is a therapeutic protease lead against IL-13 for inflammatory conditions whereby reported genetic and genomics data suggest an involvement of MMP-8. This work describes the first exploitation of human enzyme promiscuity for therapeutic applications, and reveals both starting points for protease-based therapies and potential new regulatory networks in inflammatory disease. PMID- 26548613 TI - Host-Microbe Protein Interactions during Bacterial Infection. AB - Interspecies protein-protein interactions are essential mediators of infection. While bacterial proteins required for host cell invasion and infection can be identified through bacterial mutant library screens, information about host target proteins and interspecies complex structures has been more difficult to acquire. Using an unbiased chemical crosslinking/mass spectrometry approach, we identified interspecies protein-protein interactions in human lung epithelial cells infected with Acinetobacter baumannii. These efforts resulted in identification of 3,076 crosslinked peptide pairs and 46 interspecies protein protein interactions. Most notably, the key A. baumannii virulence factor, OmpA, was identified as crosslinked to host proteins involved in desmosomes, specialized structures that mediate host cell-to-cell adhesion. Co immunoprecipitation and transposon mutant experiments were used to verify these interactions and demonstrate relevance for host cell invasion and acute murine lung infection. These results shed new light on A. baumannii-host protein interactions and their structural features, and the presented approach is generally applicable to other systems. PMID- 26548616 TI - The stage-value model: Implications for the changing standards of care. AB - The standard of care is a legal and professional notion against which doctors and other medical personnel are held liable. The standard of care changes as new scientific findings and technological innovations within medicine, pharmacology, nursing and public health are developed and adopted. This study consists of four parts. Part 1 describes the problem and gives concrete examples of its occurrence. The second part discusses the application of the Model of Hierarchical Complexity on the field, giving examples of how standards of care are understood at different behavioral developmental stage. It presents the solution to the problem of standards of care at a Paradigmatic Stage 14. The solution at this stage is a deliberative, communicative process based around why certain norms should or should not apply in each specific case, by the use of "meta-norms". Part 3 proposes a Cross-Paradigmatic Stage 15 view of how the problem of changing standards of care can be solved. The proposed solution is to found the legal procedure in each case on well-established behavioral laws. We maintain that such a behavioristic, scientifically based justice would be much more proficient at effecting restorative legal interventions that create desired behaviors. PMID- 26548615 TI - Impact of harmful use of alcohol on the sedation of critical patients on mechanical ventilation: A multicentre prospective, observational study in 8 Spanish intensive care units. AB - PURPOSE: To evaluate the impact of a history of harmful use of alcohol (HUA) on sedoanalgesia practices and outcomes in patients on mechanical ventilation (MV). METHODS: A prospective, observational multicentre study was made of all adults consecutively admitted during 30 days to 8 Spanish ICUs. Patients on MV >24h were followed-up on until discharge from the ICU or death. Data on HUA, smoking, the use of illegal (IP) and medically prescribed psychotropics (MPP), sedoanalgesia practices and their related complications (sedative failure [SF] and sedative withdrawal [SW]), as well as outcome, were prospectively recorded. RESULTS: A total of 23.4% (119/509) of the admitted patients received MV >24h; 68.9% were males; age 57.0 (17.9) years; APACHE II score 18.8 (7.2); with a medical cause of admission in 53.9%. Half of them consumed at least one psychotropic agent (smoking 27.7%, HUA 25.2%; MPP 9.2%; and IP 7.6%). HUA patients more frequently required PS (86.7% vs. 64%; p<0.02) and the use of >2 sedatives (56.7% vs. 28.1%; p<0.02). HUA was associated to an eightfold (p<0.001) and fourfold (p<0.02) increase in SF and SW, respectively. In turn, the duration of MV and the stay in the ICU was increased by 151h (p<0.02) and 4.4 days (p<0.02), respectively, when compared with the non-HUA group. No differences were found in terms of mortality. CONCLUSIONS: HUA may be associated to a higher risk of SF and WS, and can prolong MV and the duration of stay in the ICU in critical patients. Early identification could allow the implementation of specific sedation strategies aimed at preventing these complications. PMID- 26548617 TI - [Psychiatric disorders and associated factors in patients with epilepsy in Fez, Morocco]. AB - BACKGROUND: The prevalence of psychiatric disorders in epileptic patients remains unclear. OBJECTIVE: This study was conducted in order to determine the prevalence and nature of the psychiatric disorders and the associated factors in patients with idiopathic epilepsy. METHODS: A cross-sectional study was conducted over a period of eighteen months in the psychiatric unit of the University Hospital Hassan II of Fez (Morocco). A questionnaire was completed by the included patients, which specified: the socio-demographic data, personal and family history, and the clinical features of epilepsy and its management. Psychiatric disorders were identified by the Mini International Neuropsychiatric Interview test (MINI). The severity of the depression and anxiety symptoms was investigated using the Beck Depression Inventory (BDI) and the Hamilton Rating Scale. RESULTS: Eighty-nine patients met the inclusion criteria. The average age of patients was 29.7+/-10.8years. Mood disorders were the leading psychiatric comorbidity: 32.6% among which 25.8% of major depressive episodes, 15.7% of dysthymia and 2.2% of hypomanic episodes. Anxiety disorders came second: 28.1% (among which 19.1% panic disorder, 13.5% agoraphobia, 12.4% generalized anxiety disorder, 10.1% social phobia and 4.5% post-traumatic stress disorder). Female gender, unemployment and poor compliance to antiepileptic drugs are all risk factors for the occurrence of psychiatric disorders in this population. PMID- 26548618 TI - Daily dynamics in sleep and behavior of young African-American children: A convoluted dyad?! AB - Prior research has provided evidence that in children sleep and behavior are related. We aimed to determine the association between naturalistic daily variations in sleep and behavioral functioning. African American children, 5.4+/ 1.7years old, living on the south side of Chicago participated in a repeated measures study to assess this sleep-behavior link. Data was obtained from three separate two-week periods of 24-hour actigraphy and the parental version of the Behavioral Assessment System for Children. Canonical correlations analyses were applied to investigate the relation between individual changes in sleep and behavior. After 1-month, weekday average sleep duration primarily related to internalizing behaviors, while within-child variability of sleep related to behavioral changes which may involve internalizing and externalizing symptoms. Week-weekend differences in sleep associated with maladaptive social skills. Over a 6-week period, sleep onset latency and sleep offset latency related to behavioral symptoms and maladaptive skills. Over a period of 3-months, sleep associated with symptomatic behaviors while the adverse impact of within-child variability of sleep attenuated. Alternatively, the week-weekend differences in bedtime, wake-up time, wake after sleep onset and sleep onset latency in particular related to internalizing and externalizing behavior problems. Findings showed that poor sleep related to dysfunctional behaviors. While maladaptive at the beginning, they may develop into symptomatic behaviors with potentially internalizing characteristics. As time goes on, individual changes in sleep onset and offset might be important clinical markers of a chronic 'social dysregulation'. Continued sufficient and regular sleep may improve daytime and nighttime behavioral regulation in early childhood. PMID- 26548620 TI - Establishment of mesenteric venous thrombosis in a porcine model using a transhepatic endovascular approach. AB - PURPOSE: By using endovascular techniques, we set up an animal model of mesenteric venous thrombosis to avoid surgical laparotomy. MATERIALS AND METHODS: Ten pigs underwent percutaneous transhepatic puncture to create animal model of acute superior mesenteric venous thrombosis. Experimental animals were injected with thrombin via indwelling catheter, while sham-operated animals with receiving physiological saline instead of thrombin. Animals were divided into three groups according to the time of thrombosis: the control (n=3, sham group), group A (n=3, 24h follow up) and group B (n=4, 72 h follow up). Blood samples were collected and tested at the baseline and end of the experiment from the systemic circulation (jugular vein). A pathologist, blinded to the performed interventions, graded the ischemic lesions. RESULTS: Nine pigs were successfully conducted MVT model, while one died of liver rupture during the experiment. White blood cell (WBC) count (group A: 18.77 +/- 1.29, group B: 28.93 +/- 3.13), D dimer (group A: 8.30 +/- 1.93, group B: 17.30 +/- 2.48) and lactate dehydrogenase (LDH) (group A: 452.13 +/- 53.14, group B: 753.97 +/- 65.29) showed a rapid step up between the experimental animals and control animals (P<0.05), while hemoglobin (HB) count (group A: 106.63 +/- 3.84, group B: 90.00 +/- 2.43) and albumin (group A: 35.83 +/- 1.15, group B: 27.60 +/- 1.44) a steady decline (P<0.05). Changes of these parameters correlated with duration of mesenteric ischemia by statistical analysis (P<0.05). CONCLUSION: The endovascular approach in this minimally invasive porcine model of mesenteric venous thrombosis was feasible. Moreover, further animal studies are underway to evaluate the effectiveness and reproducibility of endovascular technique for MVT model. PMID- 26548621 TI - Is platelet transfusion the solution to reverse platelet inhibition in patients on triple antiplatelet therapy? PMID- 26548619 TI - Venous thromboembolism in patients with glioblastoma multiforme: Findings of the RIETE registry. AB - BACKGROUND: There is uncertainty about the optimal therapy of venous thromboembolism (VTE) in patients with glioblastoma multiforme (GBM). METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in patients with GBM, other cancers and in patients without cancer. RESULTS: As of September 2014, 53,546 patients have been recruited in RIETE. Of these, 72 (0.13%) had GBM and 11,811 (22%) had other cancers. Most patients in all 3 subgroups received initial therapy with low-molecular-weight heparin (LMWH), but those with GBM received slightly lower doses than those with other cancers or without cancer. Then, most patients with GBM continued on LMWH for long-term therapy, at similar doses than those in the other subgroups. During the course of anticoagulation (mean, 202 days), 3 patients with GBM presented VTE recurrences (10.9 per 100 patient-years; 95% CI: 2.76-29.5) and 4 suffered major bleeding (one intracranial) (14.5 bleeds per 100 patient-years; 95%CI: 4.60 34.9). Compared with patients with other cancers, those with GBM had a similar rate of VTE recurrences and major bleeds, but had a higher rate of extracranial hematoma (p<0.05). Compared with VTE patients without cancer, those with GBM had a higher rate of PE recurrences (p<0.01) and major bleeding (p<0.001), particularly extracranial hematoma (p<0.001). CONCLUSIONS: Patients with GBM and VTE had a similar rate of VTE recurrences or major bleeds during the course of anticoagulant therapy than those with other cancers. PMID- 26548622 TI - Progesterone modulates the LPS-induced nitric oxide production by a progesterone receptor independent mechanism. AB - Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. PMID- 26548623 TI - Cyclooxygenase-2 inhibitors in lung cancer treatment: Bench to bed. AB - The most common and leading cause of cancer-related death in men is lung cancer. Despite the recent advances in chemotherapy, advanced lung cancer still remains incurable. For this, the understanding of molecular mechanisms involved in lung carcinogenesis is necessary to provide potentially effective therapeutic targets for the treatment of lung cancer, and thus the therapeutic limitations can be overcome. Cyclooxygenase-2 (COX-2) is an important inflammation factor that is reported to be up-regulated in different cancers. A number of COX-2 inhibitors have been developed, but most of them are restricted due to the different risk factors. Currently, the FDA has allowed celecoxib to remain on the market but advised physicians to apply this drug with alternative therapies or to use at a low dosage. Some other COX-2 inhibitors, such as, apricoxib and etoricoxib are under critical investigation currently. Celecoxib is being tested in clinical trials against lung cancer, as a single agent or in combination with other agents. Recent studies have suggested celecoxib as a feasible and clinically active regimen in the treatment of patients with lung cancer. However, more clinical trials are necessary for the better understanding of the role of selective COX-2 inhibitors in the prevention and treatment of lung cancer along with their assessment of toxicity. In this review, we have discussed the mechanism of actions of COX-2 in cancer progression and the therapeutic use of COX-2 inhibitors in the treatment of lung cancer with subsequent clinical studies and future management. PMID- 26548625 TI - Pharmacological significance of the interplay between angiotensin receptors: MAS receptors as putative final mediators of the effects elicited by angiotensin AT1 receptors antagonists. AB - The interplay between angiotensin AT1 receptors and MAS receptors relies on several inward regulatory mechanisms from renin-angiotensin system (RAS) including the functional crosstalk between angiotensin II and angiotensin-(1-7), the competitive AT1 antagonism exhibited by angiotensin-(1-7), the antagonist feature assigned to AT1/MAS heterodimerization on AT1 signaling and the AT1 mediated downregulation of angiotensin-converting enzyme 2 (ACE2). Recently, such interplay has acquired an important significance to RAS Pharmacology since a few studies have supporting strong evidences that MAS receptors mediate the effects elicited by AT1 antagonists. The present Perspective provides an overview of the regulatory mechanisms involving AT1 and MAS receptors, their significance to RAS Pharmacology and the future directions on the interplay between angiotensin receptors. PMID- 26548624 TI - Dasatinib inhibits TGFbeta-induced myofibroblast differentiation through Src-SRF Pathway. AB - Persistent myofibroblast differentiation is a hallmark of fibrotic diseases. Myofibroblasts are characterized by de novo expression of alpha smooth muscle actin (alphaSMA) and excess fibronectin assembly. Recent studies provide conflicting reports on the effects of tyrosine kinase inhibitor dasatinib on myofibroblast differentiation and fibrosis. Also, it is not fully understood whether dasatinib modulates myofibroblast differentiation by targeting Src kinase. Herein, we investigated the effect of dasatinib on cSrc and transforming growth factor-beta (TGFbeta)-induced myofibroblast differentiation in vitro. Our results indicated that selective Src kinase inhibition using PP2 mimicked the effect of dasatinib in attenuating myofibroblast differentiation as evident by blunted alphaSMA expression and modest, but significant inhibition of fibronectin assembly in both NIH 3T3 and fibrotic human lung fibroblasts. Mechanistically, our data showed that dasatinib modulates alphaSMA synthesis through Src kinase mediated modulation of serum response factor expression. Collectively, our results demonstrate that dasatinib modulates myofibroblast differentiation through Src-SRF pathway. Thus, dasatinib could potentially be a therapeutic option in fibrotic diseases. PMID- 26548627 TI - A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors. AB - A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co-occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC 115, the MAPK1-mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit alpha (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase epsilon (POLE1), ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3alpha (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease. PMID- 26548628 TI - In ICU state anxiety is not associated with posttraumatic stress symptoms over six months after ICU discharge: A prospective study. AB - BACKGROUND: Posttraumatic stress symptoms are common after intensive care treatment. The influence of anxiety during critical illness on the development of posttraumatic stress symptoms needs to be investigated. OBJECTIVE: To determine the association between anxiety during critical illness (state and trait components) and posttraumatic stress symptoms over six months after ICU discharge. METHODS: Prospective study including 141 patients admitted >=24h to a closed mixed adult ICU in a tertiary hospital. State anxiety was assessed with the Faces Anxiety Scale during ICU stay. Trait anxiety was measured with the State-Trait Anxiety Inventory Form Y-2. Posttraumatic stress symptoms were measured at three and six months after ICU discharge using the Post-Traumatic Stress Symptoms 10-Question Inventory. Clinical and demographical data were also collected. Mixed effect regression models were used to determine if state and trait anxiety were factors significantly associated with posttraumatic stress symptoms over time. RESULTS: Moderate to severe levels of state anxiety in ICU were reported by 81 (57%) participants. Levels of trait anxiety (median 36 IQR: 29-47) were similar to the Australian population. High levels of posttraumatic stress symptoms occurred at three (n=19, 19%) and six months (n=15, 17%). Factors independently associated with posttraumatic stress symptoms were trait anxiety (2.2; 95% CI, 0.3-4.1; p=0.02), symptoms of anxiety after ICU discharge (0.6; 95% CI, 0.2-1.1; p=0.005), younger age (-1.4; 95% CI, -2.6 to -0.2; p=0.02) and evidence of mental health treatment prior to the ICU admission (5.2; 95% CI, 1.5 8.9; p=0.006). CONCLUSIONS: Posttraumatic stress symptoms occurred in a significant proportion of ICU survivors and were significantly associated with higher levels of trait anxiety, younger age, mental health treatment prior to the ICU admission and more symptoms of anxiety after ICU discharge. Early assessment and interventions directed to reduce state and trait anxiety in ICU survivors may be of benefit. PMID- 26548630 TI - Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice. AB - Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96 h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation. PMID- 26548631 TI - Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis. AB - PURPOSE: We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. METHODS: Rat fetuses (n=117) with surgically created gastroschisis were divided into three groups: untreated animals (n=62) and two groups receiving volume-matched intraamniotic injections of either saline (n=25) or 2 * 10(6) cells/mL of syngeneic, labeled afMSCs (n=30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P<0.05). RESULTS: Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P=0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P=0.003/0.05/<0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P=0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect. CONCLUSIONS: Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis. PMID- 26548629 TI - Request of thyroid function tests from Primary Care in Spain. AB - BACKGROUND AND OBJECTIVES: Laboratory tests are crucial for diagnosis and monitoring of thyroid disorders. It is therefore necessary to study the pattern and variability in requests of thyroid function tests. The study objectives were to compare the inter-regional variability in the request of laboratory thyroid tests by general practitioners (GPs) in Spain, and to investigate the potential economic savings if the goals set for some suitability indicators were reached. METHODS: Test requests per 1,000 inhabitants and test ratios (free thyroxine (FT4)/thyrotropin (TSH), free triiodothyronine (FT3)/TSH, thyroglobulin antibody (TgAb)/peroxidase antibody (TPOAb)) were compared between the different areas, according to their setting, location, and management. The resulting savings if each department achieved the goals for indicator (0.25 for FT4/TSH, 0.1 for FT3/TSH) were estimated. RESULTS: Seventy-six laboratories covering a population of 17,679,195 inhabitants participated in the study. TSH was requested significantly less in urban-rural areas, and the requests for FT3/1,000 inhabitants, FT3/TSH, and TgAb/TPOAb were higher in departments with private management. The savings generated if specifications for the ratios of related tests were met would be 937,260.5 ?. CONCLUSIONS: The high variability reported in requests for thyroid function and autoimmunity tests in Spain suggests the need for implementing strategies to improve use of such tests. PMID- 26548632 TI - Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes. AB - G protein-coupled receptors (GPCR) are one of the most important targets for therapeutics due to their abundance and diversity. The G protein-coupled receptor for thrombin can transactivate protein tyrosine kinase receptors (PTKR) and we have recently established that it can also transactivate serine/threonine kinase receptors (S/TKR). A comprehensive knowledge of the signalling pathways that GPCR transactivation elicits is necessary to fully understand the implications of both GPCR activation and the impact of target drugs. Here, we demonstrate that thrombin elicits dual transactivation-dependent signalling pathways to stimulate mRNA expression of glycosaminoglycan synthesizing enzymes chondroitin 4-O sulfotransferase 1 and chondroitin sulfate synthase 1. The PTKR mediated response involves matrix metalloproteinases and the phosphorylation of the MAP kinase Erk. The S/TKR mediated response differs markedly and involves the phosphorylation of Smad2 carboxy terminal serine residues and does not involve matrix metalloproteinases. This work shows that all of the thrombin mediated signalling to glycosaminoglycan synthesizing enzyme gene expression occurs via transactivation-dependent pathways and does not involve transactivation independent signalling. These findings highlight the complexity of thrombin mediated transactivation signalling and the broader implications of GPCR targeted therapeutics. PMID- 26548633 TI - Adenine nucleotide translocase 1 overexpression protects cardiomyocytes against hypoxia via increased ERK1/2 and AKT activation. AB - The influence of mitochondrial function on intracellular signalling is currently under intense investigation. In this regard, we analysed the effect of adenine nucleotide translocase 1 (ANT1), which facilitates the exchange of ADP and ATP across the mitochondrial membrane, on cell-protective survival signalling under hypoxia. ANT1 overexpression enhanced the survival rate in hypoxic cardiomyocytes. The effect was related to stabilization of the mitochondrial membrane potential, suppression of caspase 3 activity, and a reduction in DNA fragmentation. Activation of the cell-protective signalling proteins extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (AKT) was substantially higher in hypoxic ANT1-transgenic (ANT1-TG) cardiomyocytes than in wild-type cardiomyocytes. Kinase activation was associated with significantly higher expression of hypoxia-inducible factor 1alpha, which induces glycolytic pathway to stabilize ATP production. Accordingly, ANT1-TG cardiomyocytes exhibited earlier and stronger activation of lactate dehydrogenase and a higher ATP content. Treatment with PD980559 and triciribine, inhibitors of ERK1/2 and AKT activation, respectively, abolished cell protection in hypoxic ANT1-TG cardiomyocytes. Inhibition of ANT by carboxyatractyloside prevented the increase in ERK1/2 and AKT phosphorylation and eliminated the cell protective program in hypoxic ANT1-TG cardiomyocytes. In conclusion, the cytoprotective effect observed in hypoxic ANT1-overexpressing cardiomyocytes involves an interdependence between ANT1, activation of ERK1/ERK2 and AKT, and induction of the survival processes regulated by these kinases. PMID- 26548634 TI - Rotator cuff rehabilitation: current theories and practice. AB - A fully functioning, painless shoulder joint is essential to maintain a healthy, normal quality of life. Disease of the rotator cuff tendons (RCTs) is a common issue that affects the population, increasing with age, and can lead to significant disability and social and health costs. RCT injuries can affect younger, healthy patients and the elderly alike, and may be the result of trauma or occur as a result of chronic degeneration. They can be acutely painful, limited to certain activities or completely asymptomatic and incidental findings. A wide variety of treatment options exists ranging from conservative local and systemic pain modalities, to surgical fixation. Regardless of management ultimately chosen, physiotherapy of the RCT, rotator cuff muscles and surrounding shoulder girdle plays an essential role in proper treatment. Length of treatment, types of therapy and timing may vary if therapy is definitive care or part of a postoperative protocol. Allowing time for adequate RCT healing must always be considered when implementing ROM and strengthening after surgery. With current rehabilitation methods, patients with all spectrums of RCT pathology can improve their function, pain and quality of life. This manuscript reviews current theories and practice involving rehabilitation for RCT injuries. PMID- 26548635 TI - Human resources for research: building bridges through the Diaspora. AB - BACKGROUND: The collaboration of scientists between the developed and the developing world is an opportunity to reverse the 'brain drain' and to enable 'brain circulation'. OBJECTIVE: Attracting alumni from the Diaspora to strengthen the development of talented scientists will strengthen research in Africa. DESIGN: In 2010, the Faculty of Health Sciences at the University of the Witwatersrand, South Africa (SA), created an Alumni Diaspora Programme to boost international research collaboration and networking between leading medical and health sciences alumni who now live and work at academic institutions abroad with academic colleagues 'back home'. Based in Johannesburg, a gateway city attracting researchers from all over sub-Saharan Africa, this programme has the potential to capitalise on some of the intellectual capacity that was lost, mostly during the decades of apartheid, and to strengthen capacity, not just in SA, but across the continent. RESULTS AND CONCLUSIONS: The goal of this review is to highlight how this programme has stimulated collaborations and networking with international alumni. PMID- 26548636 TI - Genetic factors affecting drug disposition in Asian cancer patients. AB - INTRODUCTION: In the era of genomic medicine, it is increasingly recognized that ethnogeographic differences in drug pharmacology exist between Asian and other populations. This is particularly pertinent to oncology, where drugs forming the backbone of chemotherapy often have narrow therapeutic windows and are frequently dosed close to maximally tolerable levels. AREAS COVERED: At the population level, ancestry is important because historical-biogeographical confluences have shaped population genetics and pharmacoethnicity in the Asian race through allelic differentiation and interethnic differences in inheritance patterns of linkage disequilibrium. At the individual level, cis- and trans-acting germline polymorphisms and somatic mutations in genes encoding drug-metabolizing enzymes and transporters act in a multifactorial manner to determine drug disposition phenotype and clinical response in Asian cancer patients. A growing body of evidence also finds that complex genetic interactions and regulation, including a multiplicity of gene control mechanisms, are increasingly implicated in genotype phenotype correlates than has hitherto been appreciated--potentially serving as the mechanistic links between hits in non-coding regions of genome-wide association studies and drug toxicity. Together, these genetic factors contribute to the clinical heterogeneity of drug disposition in Asian cancer patients. EXPERT OPINION: This topic has broad relevance for the optimization and individualization of anticancer strategies in Asians. PMID- 26548637 TI - Electromyography as a new means of navigation during endotracheal intubation. AB - This study tested a method of using rapid analysis of electromyographic response patterns to electrical stimulation to enable real-time navigation during endotracheal intubation. An electromyographic response detection device was constructed and integrated into a standard endotracheal tube. The rebound rates of the response voltages were measured in the trachea and oesophagus after stimulation in an acute study performed in three freshly euthanized male Suffolk sheep. In a blind study, a physician attempted to identify the tissue type solely from the electrical response signals. In the acute study, the observed rebound rate was found to be significantly faster in tracheal tissue (2.21 * 10(-3) V s( 1)) than in oesophageal tissue (3.45 * 10(-2) V s(-1); p = 0.000 05). In the blind study, the physician correctly determined the oesophagus response rate seven out of eight times and the tracheal rate eight out of nine times. These results suggest that electromyographic responses can be used to accurately differentiate tracheal from oesophageal tissue during ETT insertion, thus offering a valuable new means of enhancing patient safety. PMID- 26548638 TI - Respiratory rate estimation during triage of children in hospitals. AB - Accurate assessment of a child's health is critical for appropriate allocation of medical resources and timely delivery of healthcare in Emergency Departments. The accurate measurement of vital signs is a key step in the determination of the severity of illness and respiratory rate is currently the most difficult vital sign to measure accurately. Several previous studies have attempted to extract respiratory rate from photoplethysmogram (PPG) recordings. However, the majority have been conducted in controlled settings using PPG recordings from healthy subjects. In many studies, manual selection of clean sections of PPG recordings was undertaken before assessing the accuracy of the signal processing algorithms developed. Such selection procedures are not appropriate in clinical settings. A major limitation of AR modelling, previously applied to respiratory rate estimation, is an appropriate selection of model order. This study developed a novel algorithm that automatically estimates respiratory rate from a median spectrum constructed applying multiple AR models to processed PPG segments acquired with pulse oximetry using a finger probe. Good-quality sections were identified using a dynamic template-matching technique to assess PPG signal quality. The algorithm was validated on 205 children presenting to the Emergency Department at the John Radcliffe Hospital, Oxford, UK, with reference respiratory rates up to 50 breaths per minute estimated by paediatric nurses. At the time of writing, the authors are not aware of any other study that has validated respiratory rate estimation using data collected from over 200 children in hospitals during routine triage. PMID- 26548639 TI - Prediction of the endocrine disruption profile of pesticides. AB - Numerous manmade chemicals released into the environment can interfere with normal, hormonally regulated biological processes to adversely affect the development and reproductive functions of living species. Various in vivo and in vitro tests have been designed for detecting endocrine disruptors, but the number of chemicals to test is so high that to save time and money, (quantitative) structure-activity relationship ((Q)SAR) models are increasingly used as a surrogate for these laboratory assays. However, most of them focus only on a specific target (e.g. estrogenic or androgenic receptor) while, to be more efficient, endocrine disruption modelling should preferentially consider profiles of activities to better gauge this complex phenomenon. In this context, an attempt was made to evaluate the endocrine disruption profile of 220 structurally diverse pesticides using the Endocrine Disruptome simulation (EDS) tool, which simultaneously predicts the probability of binding of chemicals on 12 nuclear receptors. In a first step, the EDS web-based system was successfully applied to 16 pharmaceutical compounds known to target at least one of the studied receptors. About 13% of the studied pesticides were estimated to be potential disruptors of the endocrine system due to their high predicted affinity for at least one receptor. In contrast, about 55% of them were unlikely to be endocrine disruptors. The simulation results are discussed and some comments on the use of the EDS tool are made. PMID- 26548640 TI - The potential of whole genome NGS for infectious disease diagnosis. AB - Non-targeted identification of microbes is now possible directly in biological samples, based on whole-genome-NGS (WG-NGS) techniques that allow deep sequencing of nucleic acids, data mining and sorting out of sequences of pathogens without any a priori hypothesis. WG-NGS was first only used as a research tool due to its cost, complexity and lack of standardization. Recent improvements in sample preparation and bioinformatics pipelines and decrease in cost now allow actionable diagnostics in patients. The potency and limits of WG-NGS and possible future indications are discussed here. WG-NGS will likely soon become a standard procedure in microbiological diagnosis. PMID- 26548641 TI - Using carer biographical narratives to explore factors involved in proxy reporting of quality of life in people with dementia. AB - OBJECTIVES: Quality of life is an important focus of research on dementia, with interest in direct reports of people with dementia and proxy reports of their carers. By exploring the subjective perspectives of unpaid family carers and paid care workers, this study aims to understand how carers construct meaning in narratives about quality of life with dementia. METHOD: A case-centred approach involved biographical narrative interviews with 10 carers to explore what was important for people with dementia to have a good quality of life. Detailed narrative analysis attended to the linguistic and structural features of accounts to consider how dementia is conceptualised by carers in the framing of quality of life. RESULTS: An individual's perception of how dementia impacts on awareness and behaviour was central to their understanding of quality of life. Carers who constructed dementia as a loss of skills and abilities were able to represent quality of life in positive terms despite the challenges of dementia. Carers who constructed dementia as eroding identity represented quality of life less positively and centred on their own means of coping with a challenging care situation. CONCLUSION: Findings highlight the importance of helping carers develop positive constructions of quality of life that are associated with understanding dementia as a loss of skills and abilities, rather than as a loss of self. Engaging with subjectivity in carers' biographical narrative accounts is important in the development of quality of life assessment to understand the meanings and emotions that underlie proxy perspectives. PMID- 26548642 TI - Increased Nonalternans Repolarization Variability Precedes Ventricular Tachycardia Onset in Patients with Implantable Defibrillators. AB - BACKROUND: T-wave alternans (TWA) is associated with ventricular tachycardia (VT). Nonalternans repolarization variability (NARV) precedes VT in certain experimental models, but its link to clinical arrhythmia is unproven. This study was conducted to determine if NARV increases prior to VT in patients with implantable cardioverter defibrillators (ICDs). METHODS: TWA and NARV were calculated from shock-channel electrograms preceding onset of VT or non-VT events in patients with an ICD. In each patient, presence of both a VT and a non-VT event with the same QRS morphology before the event was required. Mixed linear model was used for data analysis, using heart rate (HR) and the number of analyzed beats as covariates. RESULTS: Five hundred and sixty-eight events from 64 patients (males/females 51/13, 67 +/- 13 years) were analyzed. HR preceding non-VT events was higher than before VT events (RR interval 595 +/- 159 vs 706 +/ 111 ms; P < 0.0001). Both TWA and NARV increased with increasing HR (P < 0.001). TWA decreased with increasing number of analyzed beats. When controlled for number of analyzed beats and HR, both TWA and NARV were higher before VT than before non-VT events (P < 0.002 and P < 0.0005, respectively). CONCLUSIONS: NARV is elevated prior to spontaneous VT onset. Both NARV and TWA increase with HR. The decrease of TWA with increasing number of analyzed beats may indicate contamination with NARV or noise when only a small number of beats is available for analysis. NARV might be useful for VT prediction in the future. PMID- 26548643 TI - Activating transcription factor 3--an endogenous inhibitor of myocardial ischemia reperfusion injury (Review). AB - Coronary heart diseases, particularly acute coronary syndrome, have increased in morbidity and mortality in recent decades. Percutaneous coronary intervention, coronary artery bypass grafting and thrombolytic agents are effective strategies to rescue the infarcted myocardium. In addition to acute myocardial infarction, the resulting myocardial ischemia-reperfusion injury (MIRI) leads to serious secondary injury of the heart. Studies have demonstrated that activating transcription factor (ATF)/cyclic adenosine monophosphate response element binding family member ATF3 had a negative regulatory role in IRI, particularly in the kidney, cerebrum and liver. The present review expounded the expression characteristics of ATF3 and its protective effects against MIRI, providing a theoretical basis for the overexpression of ATF3 in the myocardium as a promising gene-therapeutic strategy for MIRI. PMID- 26548644 TI - Complex mitonuclear interactions and metabolic costs of mating in male seed beetles. AB - The lack of evolutionary response to selection on mitochondrial genes through males predicts the evolution of nuclear genetic influence on male-specific mitochondrial function, for example by gene duplication and evolution of sex specific expression of paralogs involved in metabolic pathways. Intergenomic epistasis may therefore be a prevalent feature of the genetic architecture of male-specific organismal function. Here, we assess the role of mitonuclear genetic variation for male metabolic phenotypes [metabolic rate and respiratory quotient (RQ)] associated with ejaculate renewal, in the seed beetle Callosobruchus maculatus, by assaying lines with crossed combinations of distinct mitochondrial haplotypes and nuclear lineages. We found a significant increase in metabolic rate following mating relative to virgin males. Moreover, processes associated with ejaculate renewal showed variation in metabolic rate that was affected by mitonuclear interactions. Mitochondrial haplotype influenced mating related changes in RQ, but this pattern varied over time. Mitonuclear genotype and the energy spent during ejaculate production affected the weight of the ejaculate, but the strength of this effect varied across mitochondrial haplotypes showing that the genetic architecture of male-specific reproductive function is complex. Our findings unveil hitherto underappreciated metabolic costs of mating and ejaculate renewal, and provide the first empirical demonstration of mitonuclear epistasis on male reproductive metabolic processes. PMID- 26548645 TI - Interface control by homoepitaxial growth in pulsed laser deposited iron chalcogenide thin films. AB - Thin film growth of iron chalcogenides by pulsed laser deposition (PLD) is still a delicate issue in terms of simultaneous control of stoichiometry, texture, substrate/film interface properties, and superconducting properties. The high volatility of the constituents sharply limits optimal deposition temperatures to a narrow window and mainly challenges reproducibility for vacuum based methods. In this work we demonstrate the beneficial introduction of a semiconducting FeSe(1-x)Te(x) seed layer for subsequent homoepitaxial growth of superconducting FeSe(1-x)Te(x) thin film on MgO substrates. MgO is one of the most favorable substrates used in superconducting thin film applications, but the controlled growth of iron chalcogenide thin films on MgO has not yet been optimized and is the least understood. The large mismatch between the lattice constants of MgO and FeSe(1-x)Te(x) of about 11% results in thin films with a mixed texture, that prevents further accurate investigations of a correlation between structural and electrical properties of FeSe(1-x)Te(x). Here we present an effective way to significantly improve epitaxial growth of superconducting FeSe(1-x)Te(x) thin films with reproducible high critical temperatures (>=17 K) at reduced deposition temperatures (200 degrees C-320 degrees C) on MgO using PLD. This offers a broad scope of various applications. PMID- 26548646 TI - Neuroprotection and immunomodulation by xenografted human mesenchymal stem cells following spinal cord ventral root avulsion. AB - The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 * 10(5) AT-MSCs via the lateral funiculus. Two weeks after cell administration, the animals were sacrificed and the moto neurons, T lymphocytes and cell defense nervous system were analyzed. An increased neuronal survival and partial preservation of synaptophysin-positive nerve terminals, related to GDNF and BDNF expression of AT MSCs, and reduction of pro-inflammatory reaction were observed. In conclusion, AT MSCs prevent second phase neuronal injury, since they suppressed lymphocyte, astroglia and microglia effects, which finally contributed to rat motor-neuron survival and synaptic stability of the lesioned motor-neuron. Moreover, the survival of the injected AT- MSCs lasted for at least 14 days. These results indicate that neuronal survival after lesion, followed by mesenchymal stem cell (MSC) administration, might occur through cytokine release and immunomodulation, thus suggesting that AT-MSCs are promising cells for the therapy of neuronal lesions. PMID- 26548648 TI - Corrigendum. PMID- 26548647 TI - New Norcantharidin Analogs: Synthesis and Anticancer Activity. AB - The reaction of direct condensation between S-ethyl-N-(7-oxabicyclo [2.2.1]heptane-2,3-dicarbonyl)isothiosemicarbazide (1) and primary amines was used for synthesizing new N-substituted amides of 3-(3-ethylthio-1,2,4-triazol-5 yl)-7-oxabicyclo-[2.2.1]heptane-2-carboxylic acid (2-12) as norcantharadin analogs. Moreover, the anticancer activity of the obtained compounds was studied. Among all compounds, the N-3-methylbutyl amide of 3-(3-ethylthio-1,2,4-triazol-5 yl)-7-oxabicyclo-[2.2.1]heptane-2-carboxylic acid (4) presented selective in vitro toxic and antiproliferative effects against the human hepatoma cell line Hep3B, without affecting normal human liver stellate cells (LX-2 cell line). PMID- 26548649 TI - Generating multi-atom entangled W states via light-matter interface based fusion mechanism. AB - W state is a key resource in quantum communication. Fusion technology has been proven to be a good candidate for preparing a large-size W state from two or more small-size W states in linear optical system. It is of great importance to study how to fuse W states via light-matter interface. Here we show that it is possible to prepare large-size W-state networks using a fusion mechanism in cavity QED system. The detuned interaction between three atoms and a vacuum cavity mode constitute the main fusion mechanism, based on which two or three small-size atomic W states can be fused into a larger-size W state. If no excitation is detected from those three atoms, the remaining atoms are still in the product of two or three new W states, which can be re-fused. The complicated Fredkin gate used in the previous fusion schemes is avoided here. W states of size 2 can be fused as well. The feasibility analysis shows that our fusion processes maybe implementable with the current technology. Our results demonstrate how the light matter interaction based fusion mechanism can be realized, and may become the starting point for the fusion of multipartite entanglement in cavity QED system. PMID- 26548650 TI - Direct evidence for a pressure-induced nodal superconducting gap in the Ba0.65Rb0.35Fe2As2 superconductor. AB - The superconducting gap structure in iron-based high-temperature superconductors (Fe-HTSs) is non-universal. In contrast to other unconventional superconductors, in the Fe-HTSs both d-wave and extended s-wave pairing symmetries are close in energy. Probing the proximity between these very different superconducting states and identifying experimental parameters that can tune them is of central interest. Here we report high-pressure muon spin rotation experiments on the temperature-dependent magnetic penetration depth in the optimally doped nodeless s-wave Fe-HTS Ba0.65Rb0.35Fe2As2. Upon pressure, a strong decrease of the penetration depth in the zero-temperature limit is observed, while the superconducting transition temperature remains nearly constant. More importantly, the low-temperature behaviour of the inverse-squared magnetic penetration depth, which is a direct measure of the superfluid density, changes qualitatively from an exponential saturation at zero pressure to a linear-in-temperature behaviour at higher pressures, indicating that hydrostatic pressure promotes the appearance of nodes in the superconducting gap. PMID- 26548651 TI - Proteome effects of antipsychotic drugs: Learning from preclinical models. AB - Proteome-wide expression analyses are performed in the brain of schizophrenia patients to understand the biological basis of the disease and discover molecular paths for new clinical interventions. A major issue with postmortem analysis is the lack of tools to discern molecular modulation related to the disease from dysregulation due to medications. We review available proteome-wide analysis of antipsychotic treatment in rodents, highlighting shared dysregulated pathways that may contribute to an extended view of molecular processes underlying their pharmacological activity. Fourteen proteomic studies conducted with typical and atypical antipsychotic treatments were examined; hypothesis-based approaches are also briefly discussed. Treatment with antipsychotics mainly affects proteins belonging to metabolic pathways involved in energy generation, both in glycolytic and oxidative phosphorylation pathways, suggesting antipsychotics-induced impairments in metabolism. Nevertheless, schizophrenic patients show impaired glucose metabolism and mitochondrial dysfunctions independent of therapy. Other antipsychotics-induced changes shared by different studies implicate cytoskeletal and synaptic function proteins. The mechanism can be related to the reorganization of dendritic spines resulting from neural plasticity events induced by treatments affecting neurotransmitter circuitry. However, metabolic and plasticity pathways activated by antipsychotics can also play an authentic role in the etiopathological basis of schizophrenia. PMID- 26548652 TI - Affecting Girls' Activity and Job Interests Through Play: The Moderating Roles of Personal Gender Salience and Game Characteristics. AB - Gender schema theory (GST) posits that children approach opportunities perceived as gender appropriate, avoiding those deemed gender inappropriate, in turn affecting gender-differentiated career trajectories. To test the hypothesis that children's gender salience filters (GSF-tendency to attend to gender) moderate these processes, 62 preschool girls (M = 4.5 years) were given GSF measures. Two weeks later, they played a computer game about occupations that manipulated the game-character's femininity (hyperfeminized Barbie vs. less feminized Playmobil Jane). Following game play, girls' interests in feminine activities showed an interaction of game condition and GSF: High-GSF girls showed intensified feminine activity interests only with Barbie; low-GSF girls showed no change with either character. Neither GSF nor game condition affected occupational interests. Implications for GST, individual differences, and occupational interventions are discussed. PMID- 26548653 TI - A Cucurbit[7]uril Based Molecular Shuttle Encoded by Visible Room-Temperature Phosphorescence. AB - A visible room-temperature phosphorescence (RTP) signal, generated by complexation of cururbit[7]uril (CB[7]) and bromo-substituted isoquinoline in aqueous solution, is employed to address the shuttling of a pH-controlling molecular shuttle fabricated by CB[7] and a phosphor 6-bromoisoquinoline derivative IQC[5]. The CB[7] host shuttles along the axial guest under acidic conditions, accompanied by a weak RTP emission signal, while deprotonation of the guest IQC[5] makes the CB[7] wheel locate on the phosphor group, leading to intense RTP emission. The switching RTP emission of the molecular shuttle, via pH adjusting, can be visibly identified by the naked eye. This is the first CB-based molecular shuttle with an RTP signal as the output address of its shuttling and conformation. PMID- 26548654 TI - The Links Between Stress and Depression: Psychoneuroendocrinological, Genetic, and Environmental Interactions. AB - The role of stress in the origin and development of depression may be conceived as the result of multiple converging factors, including the chronic effect of environmental stressors and the long-lasting effects of stressful experiences during childhood, all of which may induce persistent hyperactivity of the hypothalamic-pituitary-adrenal axis. These changes, including increased availability of corticotropin-releasing factor and cortisol, are also associated with hyperactivity of the amygdala, hypoactivity of the hippocampus, and decreased serotonergic neurotransmission, which together result in increased vulnerability to stress. The role of other monoaminergic neurotransmitters, genetic polymorphisms, epigenetic mechanisms, inflammatory processes, and altered cognitive processing has also been considered in the development of a comprehensive model of the interactions between different factors of vulnerability. Further understanding of the underlying mechanisms that link these factors may contribute significantly to the development of more effective treatments and preventive strategies in the interface between stress and mood disorders. PMID- 26548655 TI - Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury. AB - This study aimed to examine global and regional cerebral blood flow and amyloid burden in combat veterans with and without traumatic brain injury (TBI). Cerebral blood flow (in milliliters per minute per 100 mL) was measured by quantitative [(15)O]water, and amyloid burden was measured by [(11)C]PIB imaging. Mean global cerebral blood flow was significantly lower in veterans with TBI compared with non-TBI veterans. There were essentially no differences between groups for globally normalized regional cerebral blood flow. Amyloid burden did not differ between TBI and non-TBI veterans. Veterans who have suffered a TBI have significantly lower cerebral blood flow than non-TBI controls but did not manifest increased levels of amyloid, globally or regionally. PMID- 26548656 TI - A Diffusion Tensor Imaging Study Using a Voxel-Based Analysis, Region-of-Interest Method to Analyze White Matter Abnormalities in First-Episode, Treatment-Naive Major Depressive Disorder. AB - This study used fractional anisotropy (FA), a measure of diffusion tensor imaging, to analyze white matter abnormalities in 15 first-episode treatment naive patients with major depressive disorder (MDD) and 15 controls matched for age. An automated voxel-based analysis and a region-of-interest (ROI) method with 3T magnetic resonance imaging were used. Compared with controls, FA values were lower in the left superior longitudinal fasciculus, the left prefrontal cortex, and the left parietal region in patients with MDD. In addition, the ROI method revealed significantly lower FA values in the right hippocampus. Voxel-based analysis, a faster technique, complements the ROI method, which highlights FA values as potential biomarkers in early MDD. PMID- 26548657 TI - Rayleigh-wave dispersion reveals crust-mantle decoupling beneath eastern Tibet. AB - The Tibetan Plateau results from the collision of the Indian and Eurasian Plates during the Cenozoic, which produced at least 2,000 km of convergence. Its tectonics is dominated by an eastward extrusion of crustal material that has been explained by models implying either a mechanical decoupling between the crust and the lithosphere, or lithospheric deformation. Discriminating between these end member models requires constraints on crustal and lithospheric mantle deformations. Distribution of seismic anisotropy may be inferred from the mapping of azimuthal anisotropy of surface waves. Here, we use data from the CNSN to map Rayleigh-wave azimuthal anisotropy in the crust and lithospheric mantle beneath eastern Tibet. Beneath Tibet, the anisotropic patterns at periods sampling the crust support an eastward flow up to 100 degrees E in longitude, and a southward bend between 100 degrees E and 104 degrees E. At longer periods, sampling the lithospheric mantle, the anisotropic structures are consistent with the absolute plate motion. By contrast, in the Sino-Korean and Yangtze cratons, the direction of fast propagation remains unchanged throughout the period range sampling the crust and lithospheric mantle. These observations suggest that the crust and lithospheric mantle are mechanically decoupled beneath eastern Tibet, and coupled beneath the Sino-Korean and Yangtze cratons. PMID- 26548658 TI - Late Eocene white pines (Pinus subgenus Strobus) from southern China. AB - Fossil records indicate that the genus Pinus L. split into two subgenera by the Late Cretaceous, although subgenus Strobus (D. Don) Lemmon is less well documented than subgenus Pinus L., especially in eastern Asia. In this paper, Pinus maomingensis sp. nov. is established based on a compressed seed cone from the upper Eocene of the Maoming Basin of southern China. This species is attributed to genus Pinus, subgenus Strobus, section Quinquefoliae Duhamel, subsection Strobus Loudon based on the combination of morphological characters obtained from the cone scales, specifically from the terminal umbo, rhombic apophysis, and cuticle structure. Associated fascicles of needle leaves with deciduous sheaths and bulbous bases are recognized as Pinus sp. and also represent Pinus subgenus Strobus. This new discovery from the Maoming Basin constitutes the first megafossil record of subgenus Strobus from southern China and implies that the members of this subgenus arrived in the southern region of China by the late Eocene. The extant species of subgenus Strobus are mainly distributed in northern temperate and tropical to subtropical mountainous regions. We propose that the Maoming Basin was adjacent to a mountainous region during the late Eocene. PMID- 26548660 TI - Acid/Base and H2PO4(-) Controllable High-Contrast Optical Molecular Switches with a Novel BODIPY Functionalized [2]Rotaxane. AB - A novel multifunctional mechanically interlocked switchable [2]rotaxane R4 containing two molecular stations and rotaxane arms terminated with boron dipyrromethene (BODIPY) fluorophores and its derivatives were synthesized for the first time by CuAAC click reaction. The shuttling motion of macrocycle between the dibenzylammonium and triazolium recognition sites and the distance dependent photoinduced electron transfer process of R4 is demonstrated by utilizing external chemical stimuli (acid/base). Interestingly, the reversible self assembly process of R4 was recognized by the acid-base molecular switch strategy. Notably, two symmetrical triazolium groups acted as molecular stations, H2PO4(-) receptors, and H-bonded donors. Both [2]rotaxane R4 and thread R2 demonstrated excellent optical responses and high selectivity toward H2PO4(-) ion. The specific motion and guest-host interactions of mechanically interlocked machines (MIMs) were also further explored by quantum mechanical calculations. The thread R2 also demonstrated to enable the detection of H2PO4(-) in RAW 264.7 cells successfully. PMID- 26548659 TI - NMDA receptors promote neurogenesis in the neonatal rat subventricular zone following hypoxic-ischemic injury. AB - Evidence suggests the involvement of N-methyl-D- aspartate receptors (NMDAR) in the regulation of neurogenesis. Functional properties of NMDAR are strongly influenced by the type of NR2 subunits in the receptor complex. NR2A- and NR2B containing receptors are expressed in neonatal forebrain regions, such as the subventricular zone (SVZ). The aim of the present study was to examine the effect of the protein expression of hypoxic-ischemic injury NMDAR subunits 2A and 2B in the SVZ of neonatal rats. Expression of these and other proteins of interest was performed using immunohistochemistry. The results showed that NR2A expression was decreased at 6 h after hypoxic-ischemic injury. By contrast, a significant increase in NR2B expression was observed at 24 h after hypoxic-ischemic injury, induced by the clamping of the right common carotid artery. The functional effect of NMDAR subunits on neurogenesis was also examined by quantifying Nestin and doublecortin (DCX), the microtubule-associated protein expressed only in immature neurons. In addition, the effects of selective non-competitive NMDAR antagonist MK-801 (0.5 mg/kg), NR2B antagonist Ro25-6981 (5 mg/kg), and NR2A antagonist NVP AAM077 (5 mg/kg) administered 30 min prior to the hypoxic-ischemic injury were examined. The number of Nestin- and DCX-positive cells increased significantly 48 h after hypoxic-ischemic injury, which was reverted by the MK-801 and Ro25-6981 antagonists. Notably, NVP-AAM077 had no significant effect on the expression of Nestin and DCX. In conclusion, the results of the present study demonstrate that hypoxia-ischemia inhibited the expression of NR2A, but promoted the expression of NR2B. Furthermore, NMDAR promoted neurogenesis in the SVZ of neonatal brains. PMID- 26548661 TI - New Fluorescence Domain "Excited Multimer" Formed upon Photoexcitation of Continuously Stacked Diaroylmethanatoboron Difluoride Molecules with Fused pi Orbitals in Crystals. AB - The crystal-packing structures of seven derivatives of diaroylmethanatoboron difluoride (1 a-gBF2 ) are characterized by no overlap of the pi-conjugated main units of two adjacent molecules (type I), overlap of the benzene ring pi-orbitals of two adjacent molecules (type II), and overlap of the benzene and dihydrodioxaborinine rings pi-orbitals of adjacent molecules (type III). The crystal-packing structures govern the fluorescence (FL) properties in the crystalline states. The FL domain that is present in type I crystals, in which intermolecular orbital interactions are absent, leads to excited monomer-like FL properties. In the case of the type II crystals, the presence of intermolecular overlap of the benzene rings pi-orbitals generates new FL domains, referred to as "excited multimers", which possess allowed S0 -S1 electronic transitions and, as a result, similar FL lifetimes at longer wavelengths than the FL of the type I crystals. Finally, intermolecular overlap of the benzene and dihydrodioxaborinine ring pi-orbitals in the type III crystals leads to "excited multimer" domains with forbidden S0 -S1 electronic transitions and longer FL lifetimes at similar wavelengths as that in type I crystals. PMID- 26548662 TI - Bayesian inference of protein ensembles from SAXS data. AB - The inherent flexibility of intrinsically disordered proteins (IDPs) and multi domain proteins with intrinsically disordered regions (IDRs) presents challenges to structural analysis. These macromolecules need to be represented by an ensemble of conformations, rather than a single structure. Small-angle X-ray scattering (SAXS) experiments capture ensemble-averaged data for the set of conformations. We present a Bayesian approach to ensemble inference from SAXS data, called Bayesian ensemble SAXS (BE-SAXS). We address two issues with existing methods: the use of a finite ensemble of structures to represent the underlying distribution, and the selection of that ensemble as a subset of an initial pool of structures. This is achieved through the formulation of a Bayesian posterior of the conformational space. BE-SAXS modifies a structural prior distribution in accordance with the experimental data. It uses multi-step expectation maximization, with alternating rounds of Markov-chain Monte Carlo simulation and empirical Bayes optimization. We demonstrate the method by employing it to obtain a conformational ensemble of the antitoxin PaaA2 and comparing the results to a published ensemble. PMID- 26548664 TI - Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: an appraisal of its in vitro Behavior and tumor amelioration potential. AB - Topotecan (TPT) is indicated against a variety of solid tumors, but has restricted clinical use owing to associated pharmaceutical caveats. This study is focused at formulating a successful TPT PLGA nanosystem which ameliorates the rapid conversion of active lactone form of drug to its inactive carboxylate form and consequently improvises its efficacy. TPT PLGA nanoparticles were formulated by a double emulsion-solvent evaporation technique with sequential optimization to obtain desired particle size, PDI, zeta potential, and entrapment efficiency. Stability of TPT was ensured by maintaining an acidic pH in the drug-containing phase and the system was evaluated for in vitro-in vivo performance including cytotoxic potency. The optimized nanosystem had a particle size of 187.33 +/- 7.50 nm, a PDI of 0.179 +/- 0.05, and an entrapment efficiency of 56 +/- 1.2%. Low pH in the interior of nanoparticles stabilized the drug to remain in its active lactone form and revealed a biphasic release pattern till 15 d. Additionally, an in vitro cytotoxicity testing as well as in vivo antitumor efficacy demonstrated a significant potential of higher proliferation inhibition as compared with neat drug (TPT). Thus, the investigation summarized an innovative simple tool for developing stable TPT NPs for effective delivery for treating solid tumors. PMID- 26548665 TI - The Affordable Care Act and Implications for Health Care Services for American Indian and Alaska Native Individuals. AB - American Indian and Alaska Native (AI/AN) populations report poor physical and mental health outcomes while tribal health providers and the Indian Health Service (IHS) operate in a climate of significant under funding. Understanding how the Patient Protection and Affordable Care Act (ACA) affects Native American tribes and the IHS is critical to addressing the improvement of the overall access, quality, and cost of health care within AI/AN communities. This paper summarizes the ACA provisions that directly and/or indirectly affect the service delivery of health care provided by tribes and the IHS. PMID- 26548666 TI - A Scoping Review of the Literature: Content, Focus, Conceptualization and Application of the National Standards for Culturally and Linguistically Appropriate Services in Health Care. AB - With the aim of addressing inequalities and disparities in health care access and outcomes, in 2001 the United States Department of Health and Human Services Office of Minority Health (OMH) established National Standards for Culturally and Linguistically Appropriate Services (CLAS). In 2010 the OMH solicited public, private and government input which was incorporated into the Enhanced National CLAS Standards. To date there have been no formal reviews of the published literature on the CLAS Standards. The aim of this scoping review was to identify the scientific and professional literature related to the CLAS standards and describe the content, focus, conceptualization and application of these publications, with the goal of providing insights and directions for further research and application of the CLAS standards. PMID- 26548667 TI - Substance Use and Related Harms among Aboriginal People in Canada: A Comprehensive Review. AB - BACKGROUND: There is evidence of increasing trends in substance use and related harms among Aboriginal populations in Canada. This paper provides a review of data on alcohol, tobacco, and illicit drug use and related harms. METHODS: A comprehensive review of public data, journal publications, and grey literature published between 2000 and 2014 were reviewed if data included: people who self identify as Aboriginal and who live in Canada; drug use; and morbidity and mortality related to drug use. Data were structured by major substance categories and compared with non-Aboriginal sample data where possible. RESULTS: Over 100 documents were reviewed and revealed a disproportionate burden of substance use and harms, particularly among Aboriginal youth. Significant gaps in data exist, specifically, for urban populations. CONCLUSION: This review reinforces concerns of many Aboriginal communities and organizations in Canada as well as highlights where prevention, programming, and policy efforts might be most effective. PMID- 26548668 TI - Racial/Ethnic Differences in Cost-Related Nonadherence and Medicare Part D: A Longitudinal Comparison. AB - Little is known about whether racial and ethnic disparities in cost-related medication nonadherence (CRN) have changed since the implementation of Medicare Part D. This longitudinal study examined the impact of Part D on CRN among racial and ethnic minority Medicare beneficiaries, age 65 and older. Nationally representative data were obtained from the Prescription Drug Study and Health and Retirement Study. A differences-in-differences approach was used to compare CRN among non-Hispanic Blacks, Hispanics, and non-Hispanic Whites. The results indicate CRN was higher among the two minority groups than among non-Hispanic Whites before and after Medicare Part D. Mixed-effects logistic regression analyses show that CRN did not significantly change between pre- and post Medicare Part D for any of these three groups. However, older non-Hispanic Blacks and Hispanics had a larger reduction in CRN than non-Hispanic Whites. These findings suggest that despite Medicare Part D, racial and ethnic disparities in CRN persist. PMID- 26548669 TI - Risk of Bankruptcy among Applicants to Disability Insurance. AB - BACKGROUND: Poor health can lead to financial instability and, eventually, bankruptcy. We examined how entrance into the Social Security Disability Insurance (SSDI) program was associated with bankruptcy filings among those who had a disability and applied to the SSDI program. METHODS: We merged dockets from U.S. bankruptcy courts that cover 2000 through 2009 to administrative records on all SSDI applicants from 2000 through 2003 (adults aged > 18, N = 1,500,607). We estimated logistic regression models for bankruptcy declaration within one year of the decision to allow applicants onto the SSDI program. RESULTS: Being allowed onto the SSDI program was associated with a decreased risk of bankruptcy (adjusted odds ratio = 0.754). The association was negative and statistically significant for all age groups, including older applicants nearing eligibility for Medicare. CONCLUSIONS: The findings contribute to a growing body of research suggesting that increased aid to adults with a disability can reduce financial instability. PMID- 26548670 TI - Concordance between Individual vs. Area-Level Socioeconomic Measures in an Urban Setting. AB - Area-level socioeconomic status (SES) measures have been used as a proxy in child health research when individual SES measures are lacking, yet little is known about their validity in an urban setting. We assessed agreement between census block-group and individual-level SES measures obtained from a caregiver telephone survey in Jackson County, Missouri. Associations with prevalence of childhood overweight (OW), low birth weight (LBW), and household smoking exposure were examined using logistic regression models. Seven hundred eighty-one households were surveyed: 49% male, 76% White, mean child age 9.4 years. We found misclassification rates of 20-35% between individual vs. area-level measures of education and income; Kappa indices ranged from 0.26-0.36 indicating poor agreement. Both SES measures showed an inverse association with LBW and smoking exposure. Area-level SES measures may reflect a construct inclusive of neighborhood resources; routine substitution of these measures should be interpreted with caution, despite similar correlations with health outcomes. PMID- 26548671 TI - Invasive Cervical Cancer Incidence Disparities in New Jersey--a Spatial Analysis in a High Incidence State. AB - Although invasive cervical cancer incidence has declined, disparities persist. We identified spatial clusters of census tracts with elevated invasive cervical cancer incidence rates using New Jersey State Cancer Registry cases 20 years or older diagnosed in 2005-2009. Each cluster's population was compared with the rest of New Jersey's population on demographic and socioeconomic characteristics. Odds ratios that assessed associations between statistically significant characteristics (from a univariate comparison of cases in the clusters versus cases in the rest of New Jersey) and being a case in a cluster versus being a case in the rest of New Jersey were calculated from logistic regression models. Significant incidence clusters were identified around Newark, Trenton, and Camden. Being Black (all areas), Hispanic (Newark, Camden), unmarried (Newark), and uninsured/Medicaid-insured (Trenton) were significantly associated with being a case in these areas. These study results can be used to target invasive cervical cancer prevention efforts more effectively. PMID- 26548672 TI - The Healthy Weight Disparity Index: Why We Need It to Solve the Obesity Crisis. AB - OBJECTIVE: This study assessed the usefulness of the Healthy Weight Disparity Index (HWDI) to evaluate income disparities related to obesity. We compared state based body mass index (BMI) rankings with HWDI rankings. METHODS: National data from the 2010 Behavioral Risk Factor Surveillance System were used to estimate mean BMI levels in each of the 50 states (plus Washington, D.C.) by income level. Income-related disparities were described with the HWDI. Kappa statistics analyzed the concordance between the two rankings. RESULTS: State-based BMI and the HWDI rankings were not concordant. For example, Washington, D.C. was ninth for lowest mean BMI yet ranked 49th on the HWDI. West Virginia ranked 42nd and 5th, and Mississippi ranked 51st on both the BMI and HWDI, respectively. DISCUSSION: State-based BMI and HWDI rankings present divergent perspectives on the obesity crisis. We recommend adding HWDI rankings to BMI rankings to reflect fully patterns of obesity and subgroup differences. PMID- 26548673 TI - Impact of Health Workers' Strike in August 2014 on Health Services in Mombasa County Referral Hospital, Kenya. AB - INTRODUCTION: Health workers are an essential part of the health system. Health workers in Mombasa County went on strike for two weeks in August 2014 due to nonpayment of salaries. This study analysed the impact of this strike. METHODS: Monthly utilization of health services was accessed from the Kenya Health Information website. This was for general outpatient, special clinics, maternal and child health, inpatient services, maternity services, dental, and radiological services. For each indicator, monthly mean was calculated for January to July 2014. This was compared with the August monthly mean. RESULTS: Outpatient attendance declined by 64.4%, special clinics attendance by 74.2%, and deliveries by 53.5%. Inpatient admissions declined by 57.8 % and inpatient deaths by 26.3%. CONCLUSION: The August 2014 strike adversely affected health services. County governments should put in place mechanisms to avert future health workers' strike. The national government should also disburse funds to the counties on time. PMID- 26548674 TI - Inequities in Receipt of Iron and Vitamin A Supplements, and Anthelmintic Medications by Young Children in the Dominican Republic. AB - Gaps in the receipt of micronutrients and anthelmintic medications by children in low-and middle-income countries undermine efforts to reduce the burden of vitamin A and iron deficiencies, and soil transmitted helminthiases. This study aimed to identify the extent of equitable receipt of these interventions in the Dominican Republic (DR) using indices of need and socioeconomic status with data derived from the DR 2007 Demographic and Health Survey. Receipt of anthelmintic medication, iron, and vitamin A were reported for 55.0% (last six months), 30.3% (last seven days), and 24.0% (last six months) of young children, respectively. No relationships were found between indices of need and receipt of any of the interventions using bivariate and multivariate analysis. However, receipt of each intervention was related to higher maternal education, and iron was additionally related to greater family wealth. Systematic efforts to improve equitability of receipt of these core child health interventions are needed. PMID- 26548675 TI - Importance of Self-Efficacy and Knowledge to Physical Activity Behavior in Older African Americans. AB - BACKGROUND: Regular physical activity is an important lifestyle behavior for preventing or reducing the burden of osteoporosis, and for promoting optimal bone health. This report evaluates the effect of an osteoporosis education program on knowledge, self-efficacy, and initiation and/maintenance of physical activity (PA) in older African Americans. METHODS: African American adults 50 years and older (n=130) were randomly assigned to either experimental (EG) or control (CG) groups. Immediately following baseline assessment EG was offered six-weekly education sessions, using the Expanded Heath Belief Model and the CG offered same after the intervention. Main outcome measures were knowledge and self-efficacy regarding osteoporosis and engagement in PA. RESULTS: One hundred and ten (59=EG, 51=CG) participants completed all assessments. Overall, significantly higher (p<.01) mean self-efficacy and knowledge scores were observed in the EG than in the CG. Physical activity scores were positively related to self-efficacy but not knowledge scores. CONCLUSIONS: Self-efficacy is important in increasing PA in older African Americans, and emphasis on culturally appropriate strategies may improve PA and reduce the risk of osteoporotic fracture. PMID- 26548676 TI - Reported Use of Electronic Health Records to Implement Evidence Based Approaches to Colorectal Cancer Screening in Community Health Centers. AB - BACKGROUND: Community health centers (CHCs) are critical sources of primary care for medically underserved populations. Electronic health records (EHRs) are important for implementation of evidence-based approaches for cancer control. METHODS: Cross-sectional study of CHCs from the Cancer Prevention Control Research Network's community health center Clinic Characteristics Survey. Proportions of CHCs using EHR data to: 1) measure colorectal cancer screening, 2) deliver reports, and 3) provide patient reminders for colorectal cancer screening. RESULTS: Only 27% of CHCs perceive EHR system's colorectal cancer screening data as very accurate. Over half (57%) of respondent CHCs with EHRs reported it is easy or very easy to do colorectal cancer screening activities using EHR systems. CONCLUSIONS: Poor EHR data quality and cumbersome EHR systems may be significant barriers to implementation of evidence-based approaches to colorectal cancer screening in CHCs. PMID- 26548677 TI - "My House Is the Hospital": Housing and Health and Wellbeing among Persons Living with HIV/AIDS in Northern Malawi. AB - This paper reports findings of a qualitative study and draws on the political ecology of health framework to examine the links between housing and health among people living with HIV/AIDS (PLWAs) in Northern Malawi in a wider context in which the epidemic has overburdened the country's hospitals, thereby transferring the responsibility for care from government to families. The findings suggest that poor housing conditions, rooted in colonial and postcolonial policy failure, may undermine the amount, as well as the quality, of palliative care available to PLWAs. It was also found that the high cost of renting, discrimination, and poor landlord-tenant relationships imposed significant financial and emotional burden on PLWAs, thereby undermining their ability to meet dietary needs, stay healthy, and adhere to treatment. Furthermore, customary norms around property inheritance hampered women's housing security and their ability to cope with the disease. The paper concludes by making relevant policy recommendations. PMID- 26548678 TI - "The Vagina is a Very Tricky Little Thing Down There": Cervical Health Literacy among Incarcerated Women. AB - The objective of this study was to understand factors associated with women's ability to engage in cervical cancer prevention and follow-up care given ongoing criminal justice involvement. We conducted four focus groups with 45 incarcerated women to assess barriers to cervical health promotion, and used a grounded theory method to analyze data. We administered the Short Test of Functional Health Literacy in Adults to assess general health literacy as a standalone factor related to cervical health promotion. Ninety-one percent of participants had adequate health literacy scores. However, we found that the women had varying levels of cervical health literacy, which we operationalized as knowledge, beliefs, and self-efficacy related to cervical health promotion. Practitioners should establish broader interventions to empower women with criminal justice histories to take control of their own cervical health and focus on communicating updated recommendations to improve cervical health understanding, beliefs, and practices among high-risk women. PMID- 26548679 TI - Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora. AB - OBJECTIVE: This study examined knowledge, access, utilization, and barriers to use of resources among Black women exposed to multiple types of intimate partner violence in Baltimore, Maryland and the U.S. Virgin Islands (USVI). METHODS: We analyzed quantitative survey data collected by 163 women recruited from primary care, prenatal or family planning clinics in Baltimore and the USVI. In addition we analyzed qualitative data from in-depth interviews with 11 women. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using thematic analysis. RESULTS: A substantial proportion of Black women with multiple types of violence experiences lacked knowledge of, did not have access to, and did not use resources. Barriers to resource use were identified at the individual, relationship, and community levels. CONCLUSION: There is need for programs to develop awareness, promote access and utilization of resources, and eliminate barriers to resource use among abused Black women. PMID- 26548680 TI - Agreement between the Perceived and Actual Fruit and Vegetable Nutrition Environments among Low-Income Urban Women. AB - The food environment is described by two measures: store-level (actual) and individual-level (perceived). Understanding the relationship between actual and perceived fruit and vegetable (F&V) nutrition environments is important as their association may influence F&V purchases and consumption. The study objective was to assess agreement between perceived and actual environment measures of availability, quality, and affordability/price for fresh and canned/frozen F&V. African American WIC recipients (n=84) self-reported perceptions corresponding to chain food stores (n=13) which were then assessed by surveyors. Nearly 80% of participants had positive perceptions of stores' F&V availability, quality, and affordability. Store assessments indicated high F&V availability and quality and lowest prices for canned varieties. Kappa statistics, sensitivity, and specificity calculated agreement between perceived and actual measures. Results indicated slight to fair agreements. Agreements were highest for quality measures (kappa=0.25 (95% CI:0.08-0.42), p=.008). Research implications include promoting nutrition education and resident interviewing to understand F&V expectations. PMID- 26548681 TI - Factors Associated with Compliance of Blood Stool Test and Use of Colonoscopy in Underserved Communities of North Miami-Dade County, Florida. AB - INTRODUCTION: Only two-thirds of U.S. adults are compliant with screening for colorectal cancer. This study identified factors of blood stool test (BST) compliance and colonoscopy use among randomly selected households in Miami-Dade County, Florida. METHODS: This study used cross-sectional data collected 10/2009 04/2010. Analyses were restricted to 1,118 single-family homes containing a minimum of one member >= 50 years. RESULTS: Half of households were compliant with BST (55%) or completed colonoscopy (55%). Factors associated with BST compliance included retirement (adjusted odds ratio[AOR]=1.57**), being uninsured (AOR=0.64**), diagnosed morbidities (AOR=1.68**), fruit/vegetable consumption (AOR=1.60**), and using alternative medicines (AOR=1.36*). Factors associated with colonoscopy included Hispanic ethnicity (AOR=0.56**), lower education (AOR=0.66*), being single (AOR=0.65*), retirement (AOR=2.01***), being uninsured (AOR=0.61**), diagnosed morbidities (AOR=2.13***), former smoking (AOR=1.94**), and fruit/vegetable consumption (AOR=1.75***)(*p<.05;**p<.01;***p<.001). CONCLUSION: This is the first study of factors of BST and colonoscopy in Miami Dade County. These findings provide a basis for community-based interventions aimed at increasing screening within this population. PMID- 26548682 TI - Effects of Health Insurance on Tumor Stage, Treatment, and Survival in Large Cohorts of Patients with Breast and Colorectal Cancer. AB - To examine the impact of health insurance status on tumor stage at diagnosis, treatment rendered, and overall survival, we identified 52,566 breast cancer patients and 34,316 colorectal cancer patients aged 20 or older in 2007-2010 from Texas Cancer Registry. Those aged younger than 65 years without health insurance coverage had significantly higher risks of mortality than those with private health insurance regardless of tumor stage, chemotherapy, or surgery for colorectal cancer. However, in patients younger than 65 years with breast cancer, the risk of mortality was not significantly higher for those who received chemotherapy or cancer-directed surgery in patients without insurance coverage compared with those with private health insurance. In Medicare beneficiaries aged 65 years or older, risk of mortality was not significantly different between those with Medicare only and those with additional private health insurance, except an increased mortality in patients without chemotherapy for breast and colorectal cancer and in those without receiving surgery for colorectal cancer. PMID- 26548683 TI - Improving Access to Vision Care for People Who are Homeless through Eyeglasses Recycling. AB - Visual impairment disproportionately affects the health and function of people who are homeless. A common and correctable cause of visual impairment is refractive error. However, eyeglasses remain an unmet need for the poor and underinsured. This report describes eyeglasses recycling and vision screening to reduce the burden of correctable visual impairment. PMID- 26548684 TI - Implementing the Dementia Carers Support Initiative of the National Institute for Health and Care Excellence in a sub-Saharan African Setting. AB - Global estimates suggest that by 2040, over 71% of people living with dementia worldwide will reside in low- and middle-income countries, especially in sub Saharan Africa. In this region, informal caregivers, who are mostly close family members, may number over nine times the number of dementia patients. This group of carers often lacks the support they require for their exceptional effort. The United Kingdom's National Institute for Health and Care Excellence (NICE) provides access to tailored psychosocial interventions as part of a comprehensive support for carers of patients with dementia. This paper appraises organizational considerations in introducing this initiative into the resource-poor health care delivery system typical of many sub-Saharan African settings. It concludes that one initial step in that direction may be the introduction--through a developmental change management framework led by all stakeholders--of a tailored carers' information package into the routine care for dementia. PMID- 26548685 TI - Barriers and Facilitators to Engaging Communities in Gender-Based Violence Prevention following a Natural Disaster. AB - Humanitarian workers in disaster settings report a dramatic increase in gender based violence (GBV). This was true after the 2010 Haiti earthquake when women and girls lost the relative security of their homes and families. Researchers from the United States Virgin Islands and the United States mainland responded by collaborating with Haitian colleagues to develop GBV-focused strategies. To start, the research team performed a situational analysis to insure that the project was culturally, ethically, and logistically appropriate. The aim of this paper is to describe how the situational analysis framework helped the researchers effectively approach this community. Using post-earthquake Haiti as an exemplar, we identify key steps, barriers, and facilitators to undertaking a situational analysis. Barriers included logistics, infrastructure, language and community factors. Facilitators included established experts, organizations and agencies. Researchers in such circumstances need to be respectful of community members as experts and patient with local environmental and cultural conditions. PMID- 26548686 TI - Research Assistants Caught in Limbo: Considering Their Role in Quantitative, Longitudinal Research with Vulnerable Populations. AB - Research assistants (RAs) play a variety of roles that are critical in making research happen and in determining its quality and effectiveness. Yet their locus of power in the production of knowledge stands in sharp contrast to their relative powerlessness in the hierarchical research organization. This article explores the experiences of RAs engaged in a randomized controlled longitudinal field trial of a Housing First intervention for individuals experiencing homelessness and mental illness in Toronto. They encountered several unexpected effects of navigating the power ascribed to them by both study participants and community service providers. This study underscores the importance of acknowledging that RAs are the face of the research study in the field, and of better understanding implications associated with that fact, especially when marginalized populations and their providers are involved. PMID- 26548687 TI - Attaining Financial Fluency among Physicians: Start with the Students. AB - One in three chronically ill patients is unable to afford medications, food, or both. Too often, physicians do not discuss costs of care, risking decreased patient adherence. Physicians may be uncomfortable talking about prices and costs with patients because they receive little training in how to do so. The authors argue that one way of teaching providers financial fluency--defined here as physician knowledge of and comfort with discussing economic barriers to care--is to provide that training early in their careers. The concept of anchoring bias supports this argument, as it suggests that humans often rely heavily on the first piece of information obtained. An ideal training setting is the student-run community clinic, where volunteer physicians see low-income, uninsured patients, and medical students coordinate care. This early exposure trains students to expect, rather than fear, a discussion about the cost of care. These experiences should be expanded and formally evaluated. PMID- 26548688 TI - Urban Health Project: A Sustainable and Successful Community Internship Program for Medical Students. AB - BACKGROUND: Urban Health Project (UHP) is a mission and vision-driven summer internship at the University of Cincinnati College of Medicine that places first year medical students at local community agencies that work with underserved populations. At the completion of their internship, students write Final Intern Reflections (FIRs). METHODS: Final Intern Reflections written from 1987 to 2012 were read and coded to both predetermined categories derived from the UHP mission and vision statements and new categories created from the data themselves. RESULTS: Comments relating to UHP's mission and vision were found in 47% and 36% of FIRs, respectively. Positive experiences outweighed negative by a factor of eight. Interns reported the following benefits: educational (53%), valuable (25%), rewarding (25%), new (10%), unique (6%), and life-changing (5%). CONCLUSIONS: Urban Health Project is successful in providing medical students with enriching experiences with underserved populations that have the potential to change their understanding of vulnerable populations. PMID- 26548689 TI - Oral Health Status of Children Attending a Mobile Dental Clinic--A Comparative Study. AB - Periodicity of dental visits for children is based on age and disease susceptibility. Frequently mobile dental clinics are unable to provide follow-up care at recommended intervals. This study compared the oral health of children attending the mobile clinic (MC) twice with matched children by age, gender, race, and ZIP code attending for the first time. Dental charts (n=888) were reviewed and scored for decayed and filled surfaces. Seventy-eight children (mean age 9.6 years; 98.7% Hispanic) attended the clinic twice over a mean interval between visits of 1.5 years. These children had statistically significant lower rates of decay in deciduous and permanent tooth surfaces than matched children visiting the clinic for the first time (p<.05; p<.001), and significantly less decay in their deciduous and permanent teeth than at the first visit (p<.001; p<.05). Mobile clinics can be effective in decreasing the decay in teeth, even when the interval between visits is longer than current recommendations. PMID- 26548690 TI - Improving Treatment Completion Rates for Latent Tuberculosis Infection: A Review of Two Treatment Regimens at a Community Health Center. AB - BACKGROUND: Prophylactic treatment of latent tuberculosis infection (LTBI) is necessary for controlling TB in low-incidence settings. However, treatment is often limited by poor completion rates. METHODS: At a community health center serving low-income Hispanics, treatment completion among patients accepting 12 weekly doses of isoniazid (INH) plus rifapentine (RPT) administered as directly observed therapy (DOT) was compared with that among patients accepting nine months of daily self-administered INH during 2012 and 2013 (n=139). RESULTS: Among patients who agreed to treatment, INH-RPT combination therapy was associated with higher completion rates (OR 3.06; 95% CI, 1.23-7.62; p=.016) when compared to INH only. Overall completion rates were 77.8% (35/45) for INH-RPT combination therapy and 52.1% (49/94) for INH monotherapy. CONCLUSIONS: High completion rates for LTBI treatment can be achieved at a community health center using INH-RPT administered via DOT. Greater success treating with INH-RPT may be attributed to DOT strategy and a shorter treatment regimen. PMID- 26548691 TI - Results of a Health Education Message Intervention on HPV Knowledge and Receipt of Follow-up Care among Latinas Infected with High-risk Human Papillomavirus. AB - A clinic-based intervention study was conducted among high-risk human papillomavirus (HPV)-infected Latinas aged 18-64 years between April 2006 and May 2008 on the Texas-Mexico border. Women were randomly assigned to receive a printed material intervention (n=186) or usual care (n=187) and were followed at three months, six months, and 12 months through telephone surveys and review of medical records. The HPV knowledge of nearly all women had increased greatly, but only two-thirds of women reported they had received follow-up care within one year of diagnosis regardless of additional health education messaging. Our findings suggest that, regardless of type of health education messaging, Latinas living on the Texas-Mexico border are aware that follow-up care is recommended, but they may not receive this care. Individual, familial and medical care barriers to receipt of follow-up care may partially account for the higher rates of cervical cancer mortality in this region. PMID- 26548695 TI - Errata. PMID- 26548692 TI - Using a Community-Engaged Approach to Develop a Bilingual Survey about Psychosocial Stressors among Individuals of Mexican Origin. AB - Hypertension is on the rise among Hispanics and is highest among those of Mexican origin. Recent studies have found a positive association between air pollution and blood pressure and hypertension. Moreover, a link between hypertension and adverse socioeconomic conditions is well established. However, less is known about psychosocial stressors, although their impact on coronary heart disease has been shown. To address this gap in the literature, community perspectives of the health consequences of environmental exposures and psychosocial stressors experienced among the Mexican-origin population in Houston, Texas were obtained through participation in focus groups, the establishment of a Neighborhood Council of Advisors (NCA), and the testing of a pilot questionnaire. Taken together, the findings from the community were used to develop a culturally sensitive, bilingual questionnaire for an investigation of the combined effects of environmental and psychosocial stressors on hypertension among individuals of Mexican origin. PMID- 26548697 TI - Decrease of nasal airway resistance and alleviations of symptoms after balloon sinuplasty in patients with isolated chronic rhinosinusitis: a prospective, randomised clinical study. AB - OBJECTIVES: The aim of this study was to evaluate and compare the clinical outcome of balloon sinuplasty and uncinectomy for patients suffering from isolated chronic rhinosinusitis of the maxillary sinus. DESIGN: A prospective, randomised, non-blinded, controlled trial was conducted. SETTING: The study was carried out at the Department of Otolaryngology, Tampere University Hospital, Finland. PARTICIPANTS: Adult patients with symptomatic isolated chronic or recurrent rhinosinusitis without severe findings in the sinuses, as documented in the sinus' Computer Tomography scan and clinical examination, were randomised into two groups: uncinectomy and balloon sinuplasty. MAIN OUTCOME MEASURES: The variables in our study are the Sinonasal Outcome Test-22 (SNOT 22), acoustic rhinometry and rhinomanometry. These parameters were analysed preoperatively and postoperatively (after 3 and 6 months). RESULTS: The preliminary results of our study have been previously published. Both balloon sinuplasty and uncinectomy significantly improved almost all the parameters of SNOT22 (P < 0.05), with no significant difference being found between these two groups (P > 0.05). Based on rhinomanometry results, airway resistance decreased after treatment. Regarding adverse effects, balloon sinuplasty was significantly associated with a lesser risk of synechia. CONCLUSIONS: Both balloon sinuplasty and uncinectomy improved the quality of life and decreased upper airway resistance of patients with mild, isolated chronic or recurrent rhinosinusitis. The smaller risk of postoperative synechiae with balloon sinuplasty combined with its promising efficiency could partially compensate for its high material cost. PMID- 26548696 TI - Acute resistance exercise activates rapamycin-sensitive and -insensitive mechanisms that control translational activity and capacity in skeletal muscle. AB - KEY POINTS: Ribosome biogenesis is the primary determinant of translational capacity, but its regulation in skeletal muscle following acute resistance exercise is poorly understood. Resistance exercise increases muscle protein synthesis acutely, and muscle mass with training, but the role of translational capacity in these processes is unclear. Here, we show that acute resistance exercise activated pathways controlling translational activity and capacity through both rapamycin-sensitive and -insensitive mechanisms. Transcription factor c-Myc and its downstream targets, which are known to regulate ribosome biogenesis in other cell types, were upregulated after resistance exercise in a rapamycin-independent manner and may play a role in determining translational capacity in skeletal muscle. Local inhibition of myostatin was also not affected by rapamycin and may contribute to the rapamycin-independent effects of resistance exercise. ABSTRACT: This study aimed to determine (1) the effect of acute resistance exercise on mechanisms of ribosome biogenesis, and (2) the impact of mammalian target of rapamycin on ribosome biogenesis, and muscle protein synthesis (MPS) and degradation. Female F344BN rats underwent unilateral electrical stimulation of the sciatic nerve to mimic resistance exercise in the tibialis anterior (TA) muscle. TA muscles were collected at intervals over the 36 h of exercise recovery (REx); separate groups of animals were administered rapamycin pre-exercise (REx+Rapamycin). Resistance exercise led to a prolonged (6 36 h) elevation (30-50%) of MPS that was fully blocked by rapamycin at 6 h but only partially at 18 h. REx also altered pathways that regulate protein homeostasis and mRNA translation in a manner that was both rapamycin-sensitive (proteasome activity; phosphorylation of S6K1 and rpS6) and rapamycin-insensitive (phosphorylation of eEF2, ERK1/2 and UBF; gene expression of the myostatin target Mighty as well as c-Myc and its targets involved in ribosome biogenesis). The role of c-Myc was tested in vitro using the inhibitor 10058-F4, which, over time, decreased basal RNA and MPS in a dose-dependent manner (correlation of RNA and MPS, r(2) = 0.98), even though it had no effect on the acute stimulation of protein synthesis. In conclusion, acute resistance exercise stimulated rapamycin sensitive and -insensitive mechanisms that regulate translation activity and capacity. PMID- 26548698 TI - Magnetic resonance imaging assisted management in five cases of suspected quittor. AB - OBJECTIVES: Assessment of the usefulness of magnetic resonance imaging (MRI) in treatment planning in suspected cases of quittor in the horse. METHODS: Five horses with chronic discharging tracts at the level of the foot underwent MRI for treatment planning. RESULTS: The MRI examination revealed variable involvement of soft tissue and osseous structures of the foot in addition to abnormalities of the ungular cartilages in all cases. In two cases, follow-up MRI examination was performed. Four of five horses had a successful outcome, with three of these undergoing only one surgical procedure and one being managed medically. CLINICAL SIGNIFICANCE: We believe that the use of preoperative MRI facilitated accurate determination of the structures involved in cases of quittor, guiding the management, surgical approach and postoperative therapy. PMID- 26548699 TI - Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats. AB - AIMS: The aim of this study was to investigate the effect of subchronic administration of agomelatine on energy metabolism, oxidative stress markers and antioxidant defense in the brains of rats. METHODS: The animals received daily intraperitoneal injections of agomelatine (10, 30 or 50 mg/kg) or saline for 14 days. The prefrontal cortex, cerebellum, hippocampus, striatum and posterior cortex were analyzed. RESULTS: The findings showed that complex I was activated in the prefrontal cortex, cerebellum and striatum and inhibited in the posterior cortex at the 10-mg/kg dose, and inhibited in all brain areas analyzed at the 30 mg/kg and 50-mg/kg doses. Complex II was activated in the posterior cortex at the 50-mg/kg dose. Complex IV was inhibited in the striatum and posterior cortex at the 10-mg/kg dose, inhibited in the striatum at the 30-mg/kg dose and activated in the hippocampus at the 50-mg/kg dose. Creatine kinase activity was inhibited in the striatum at the 10-mg/kg and 30-mg/kg doses. Lipid peroxidation and protein carbonylation levels were not changed after the administration of agomelatine. Superoxide dismutase activity was increased in the striatum at the 10-mg/kg dose, and catalase activity was inhibited in the cerebellum at the 10 mg/kg dose and increased in the posterior cortex at the 30-mg/kg dose. CONCLUSIONS: Our results are consistent with other studies showing that some antidepressants may influence brain energy metabolism and oxidative stress parameters and expand knowledge about the effects of agomelatine in biochemical parameters in the brains of rats. PMID- 26548700 TI - Copper-catalyzed electrophilic amination using N-methoxyamines. AB - Copper-catalyzed electrophilic amination of a triarylboroxin using an N methoxyamine to give quick access to a variety of anilines was reported. The reaction was especially useful for syntheses of functionalized anilines when combined with our previously reported nucleophilic addition to N-methoxyamides. PMID- 26548701 TI - Effects of a Proline Endopeptidase on the Detection and Quantitation of Gluten by Antibody-Based Methods during the Fermentation of a Model Sorghum Beer. AB - The effectiveness of a proline endopeptidase (PEP) in hydrolyzing gluten and its putative immunopathogenic sequences was examined using antibody-based methods and mass spectrometry (MS). Based on the results of the antibody-based methods, fermentation of wheat gluten containing sorghum beer resulted in a reduction in the detectable gluten concentration. The addition of PEP further reduced the gluten concentration. Only one sandwich ELISA was able to detect the apparent low levels of gluten present in the beers. A competitive ELISA using a pepsin-trypsin hydrolysate calibrant was unreliable because the peptide profiles of the beers were inconsistent with that of the hydrolysate calibrant. Analysis by MS indicated that PEP enhanced the loss of a fragment of an immunopathogenic 33-mer peptide in the beer. However, Western blot results indicated partial resistance of the high molecular weight (HMW) glutenins to the action of PEP, questioning the ability of PEP in digesting all immunopathogenic sequences present in gluten. PMID- 26548702 TI - A nonfullerene acceptor for wide band gap polymer based organic solar cells. AB - A new 1,8-naphthalimide based planar small molecular acceptor and two benzothiadiazole based wide band gap (WBG) polymer donors P1 and P2 were synthesized for nonfullerene organic photovoltaic cells (OPVs). Devices based on fluorinated polymer P2 achieved a highly improved PCE of 3.71% with an open circuit voltage (V(oc)) of 1.07 V, which is beyond the currently known levels for nonfullerene OPVs with the V(oc) higher than 1 V. PMID- 26548703 TI - Experimental infection of rock pigeons (Columba livia) with three West Nile virus lineage 1 strains isolated in Italy between 2009 and 2012--CORRIGENDUM. PMID- 26548704 TI - Atomic and vibrational origins of mechanical toughness in bioactive cement during setting. AB - Bioactive glass ionomer cements (GICs) have been in widespread use for ~40 years in dentistry and medicine. However, these composites fall short of the toughness needed for permanent implants. Significant impediment to improvement has been the requisite use of conventional destructive mechanical testing, which is necessarily retrospective. Here we show quantitatively, through the novel use of calorimetry, terahertz (THz) spectroscopy and neutron scattering, how GIC's developing fracture toughness during setting is related to interfacial THz dynamics, changing atomic cohesion and fluctuating interfacial configurations. Contrary to convention, we find setting is non-monotonic, characterized by abrupt features not previously detected, including a glass-polymer coupling point, an early setting point, where decreasing toughness unexpectedly recovers, followed by stress-induced weakening of interfaces. Subsequently, toughness declines asymptotically to long-term fracture test values. We expect the insight afforded by these in situ non-destructive techniques will assist in raising understanding of the setting mechanisms and associated dynamics of cementitious materials. PMID- 26548707 TI - Macrophage Inflammatory Protein-1 Beta and Interferon Gamma Responses in Ugandans with HIV-1 Acute/Early Infections. AB - Control of HIV replication through CD4(+) and CD8(+) T cells might be possible, but the functional and phenotypic characteristics of such cells are not defined. Among cytokines produced by T cells, CCR5 ligands, including macrophage inflammatory protein-1 beta (MIP-1beta), compete for the CCR5 coreceptor with HIV, promoting CCR5 internalization and decreasing its availability for virus binding. Interferon (IFN)-gamma also has some antiviral activity and has been used as a read-out for T cell immunogenicity. We used cultured ELISpot assays to compare the relative contribution of MIP-1beta and IFN-gamma to HIV-specific responses. The magnitude of responses was 1.36 times higher for MIP-1beta compared to IFN-gamma. The breadth of the MIP-1beta response (45.41%) was significantly higher than IFN-gamma (36.88%), with considerable overlap between the peptide pools that stimulated both MIP-1beta and IFN-gamma production. Subtype A and D cross-reactive responses were observed both at stimulation and test level, but MIP-1beta and IFN-gamma responses displayed different effect patterns. We conclude that the MIP-1beta ELISpot would be a useful complement to the evaluation of the immunogenicity of HIV vaccines and the activity of adjuvants. PMID- 26548708 TI - Organometallic rhodium(III) and iridium(III) cyclopentadienyl complexes with curcumin and bisdemethoxycurcumin co-ligands. AB - A series of half-sandwich cyclopentadienyl rhodium(III) and iridium(III) complexes of the type [Cp*M(curc/bdcurc)Cl] and [Cp*M(curc/bdcurc)(PTA)][SO3CF3], in which Cp* = pentamethylcyclopentadienyl, curcH = curcumin and bdcurcH = bisdemethoxycurcumin as O^O-chelating ligands, and PTA = 1,3,5-triaza-7 phosphaadamantane, is described. The X-ray crystal structures of three of the complexes, i.e. [Cp*Rh(curc)(PTA)][SO3CF3] (5), [Cp*Rh(bdcurc)(PTA)][SO3CF3] (6) and [Cp*Ir(bdcurc)(PTA)][SO3CF3] (8), confirm the expected "piano-stool" geometry. With the exception of 5, the complexes are stable under pseudo physiological conditions and are moderately cytotoxic to human ovarian carcinoma (A2780 and A2780cisR) cells and also to non-tumorigenic human embryonic kidney (HEK293) cells, but lack the cancer cell selectivity observed for related arene ruthenium(II) complexes. PMID- 26548709 TI - One-pot synthesis of active copper-containing carbon dots with laccase-like activities. AB - Herein, an effective strategy for designing a new type of nanozyme, blue fluorescent laccase mimics, is reported. Active copper-containing carbon dots (Cu CDs) were synthesized through a simple, nontoxic and one-pot hydrothermal method, which showed favorable photoluminescence properties and good photostability under high-salt conditions or in a broad pH range (3.0-13.5). The Cu-CDs possessed intrinsic laccase-like activities and could catalyze the oxidation of the laccase substrate p-phenylenediamine (PPD) to produce a typical color change from colorless to brown. Poly(methacrylic acid sodium salt) (PMAA) not only was used as the carbon source and reducing agent, but also provided carboxyl groups to assist flocculation between Cu-CDs and polyacrylamide, which facilitated the removal of PPD. Importantly, the intrinsic fluorescence of the as-prepared Cu-CDs could indicate the presence of hydroquinone, one of the substrates of laccases, based on laccase mimics and fluorescence quenching. PMID- 26548710 TI - A review of the mechanisms and evidence for typical and atypical twinning. AB - The mechanisms responsible for twinning and disorders of twin gestations have been the subject of considerable interest by physicians and scientists, and cases of atypical twinning have called for a reexamination of the fundamental theories invoked to explain twin gestations. This article presents a review of the literature focusing on twinning and atypical twinning with an emphasis on the phenomena of chimeric twins, phenotypically discordant monozygotic twins, mirror image twins, polar body twins, complete hydatidiform mole with a coexistent twin, vanishing twins, fetus papyraceus, fetus in fetu, superfetation, and superfecundation. The traditional models attributing monozygotic twinning to a fission event, and more recent models describing monozygotic twinning as a fusion event, are critically reviewed. Ethical restrictions on scientific experimentation with human embryos and the rarity of cases of atypical twinning have limited opportunities to elucidate the exact mechanisms by which these phenomena occur. Refinements in the modeling of early embryonic development in twin pregnancies may have significant clinical implications. The article includes a series of figures to illustrate the phenomena described. PMID- 26548711 TI - Large-area functionalized CVD graphene for work function matched transparent electrodes. AB - The efficiency of flexible photovoltaic and organic light emitting devices is heavily dependent on the availability of flexible and transparent conductors with at least a similar workfunction to that of Indium Tin Oxide. Here we present the first study of the work function of large area (up to 9 cm(2)) FeCl3 intercalated graphene grown by chemical vapour deposition on Nickel, and demonstrate values as large as 5.1 eV. Upon intercalation, a charge density per graphene layer of 5 ? 10(13) +/- 5 ? 10(12) cm(-2) is attained, making this material an attractive platform for the study of plasmonic excitations in the infrared wavelength spectrum of interest to the telecommunication industry. Finally, we demonstrate the potential of this material for flexible electronics in a transparent circuit on a polyethylene naphthalate substrate. PMID- 26548712 TI - Quantum Dot and Polymer Composite Cross-Reactive Array for Chemical Vapor Detection. AB - A cross-reactive chemical sensing array was made from CdSe Quantum Dots (QDs) and five different organic polymers by inkjet printing to create segmented fluorescent composite regions on quartz substrates. The sensor array was challenged with exposures from two sets of analytes, including one set of 14 different functionalized benzenes and one set of 14 compounds related to security concerns, including the explosives trinitrotoluene (TNT) and ammonium nitrate. The array was broadly responsive to analytes with different chemical functionalities due to the multiple sensing mechanisms that altered the QDs' fluorescence. The sensor array displayed excellent discrimination between members within both sets. Classification accuracy of more than 93% was achieved, including the complete discrimination of very similar dinitrobenzene isomers and three halogenated, substituted benzene compounds. The simple fabrication, broad responsivity, and high discrimination capacity of this type of cross-reactive array are ideal qualities for the development of sensors with excellent sensitivity to chemical and explosive threats while maintaining low false alarm rates. PMID- 26548713 TI - Understanding the structure and function of Bacillus thuringiensis toxins. AB - As biological control agents take an expanding share of the pesticides market and the production of insect-resistant crops increases, it is essential to understand the structure and function of the active agents, the invertebrate-active toxins that are the fundamental ingredients of these control systems. The potential for these agents in industry, agriculture and medicine necessitates a thorough investigation of their activity. PMID- 26548714 TI - Cardiovascular outcomes and conventional risk factors in non-diabetic adult patients with GH deficiency: A long-term retrospective cohort study. AB - PURPOSE: To investigate the association between cardiovascular (CV) risk factors and cumulative CV events in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT). METHODS: 53 non-diabetic adult GHD patients, aged 45.4+/-14.3years, 31 females, with a median follow up of 140months, were divided into two groups based on the presence (group A) or absence (group B) of systemic hypertension. Tertiles of age and LDL-cholesterol were considered as further potential prognosticators. Cumulative CV event rates were recorded and analyzed by Kaplan-Mayer method. Differences between patients with and without events were also evaluated. RESULTS: Seventeen patients (32%) entered the group A and 36 (68%) the group B. A composite of fatal and non-fatal CV events occurred in 22.6% of patients, 47.1% in group A and 11% in group B (p=0.01), CV deaths in 3 patients (5.7%; annual death rate 0.49%), 2 of whom were in group A. At Kaplan-Mayer analysis, hypertension and age>55years were major prognosticators. The odds ratio was 7.1 (95% CI: 1.74-29.12, p<0.003) and 6.2 (95% CI: 1.54-25.04, p<0.006), respectively. LDL-cholesterol showed borderline statistical significance. Patients with CV events also had high prevalence of left ventricular hypertrophy, left atrial enlargement and subclinical systolic dysfunction. CONCLUSIONS: In this study, outcomes were mainly related to hypertension and age (partially to LDL-cholesterol), confirming that management of GHD patients must be inclusive of treatment of conventional risk factors, being as important as GHRT. Optimal blood pressure control is crucial when a target organ damage is present and in patients older than 55years. PMID- 26548715 TI - The effect of smoking on carotid intima-media thickness progression rate and rate of lumen diameter reduction. AB - OBJECTIVE: The purpose of the study was to investigate the long-term associations between smoking habits, environmental tobacco smoke exposure (ETS), carotid intima-media thickness (IMT) progression rate, and rate of lumen diameter reduction in the carotid artery during a 16-year follow-up. Another objective was to investigate if an effect of smoking on progression rate could be explained by increased low grade inflammation. METHODS: The study population included 2992 middle-aged men and women in the 1991-1994 (baseline) and the 2007-2012 (re examination) investigation of the Malmo Diet and Cancer Study cardiovascular cohort. Associations between smoking, progression of carotid IMT and lumen diameter reduction due to plaque protrusion were assessed by linear regression. RESULTS: IMT progression rates and rate of lumen diameter reduction increased from never smokers with no ETS through former, moderate and heavy smokers, even after adjustment for traditional risk factors (e.g., differences in yearly progression rates (mm/year) of maximal IMT in the carotid bifurcation compared to never smokers; former smokers 0.0074 (95% CI: 0.0018-0.0129), moderate smokers 0.0106 (95% CI: 0.0038-0.0175), and heavy smokers 0.0146 (95% CI: 0.0061 0.0230)). Former smokers showed distinct lowering of progression rates after more than five years since smoking cessation. Smoking and former smoking was associated with increased low grade inflammation, however, the effect of smoking on atherosclerotic progression rate remained fairly unchanged after such adjustment. CONCLUSION: The effect of smoking and former smoking on carotid IMT progression rates and change in lumen reduction due to plaque protrusion could not be explained by differences in traditional risk factors or low grade inflammation. PMID- 26548716 TI - Foraging decisions in wild versus domestic Mus musculus: What does life in the lab select for? AB - What does domestication select for in terms of foraging and anti-predator behaviors? We applied principles of patch use and foraging theory to test foraging strategies and fear responses of three strains of Mus musculus: wild caught, control laboratory, and genetically modified strains. Foraging choices were quantified using giving-up densities (GUDs) under three foraging scenarios: (1) patches varying in microhabitat (covered versus open), and initial resource density (low versus high); (2) daily variation in auditory cues (aerial predators and control calls); (3) patches with varying seed aggregations. Overall, both domestic strains harvested significantly more food than wild mice. Each strain revealed a significant preference for foraging under cover compared to the open, and predator calls had no detectable effects on foraging. Both domestic strains biased their harvest toward high quality patches; wild mice did not. In terms of exploiting favorable and avoiding unfavorable distributions of seeds within patches, the lab strain performed best, the wild strain worst, and the mutant strain in between. Our study provides support for hypothesis that domestic animals have more energy-efficient foraging strategies than their wild counterparts, but retain residual fear responses. Furthermore, patch-use studies can reveal the aptitudes and priorities of both domestic and wild animals. PMID- 26548717 TI - Attentional shifts in categorization learning: Perseveration but not learned irrelevance. AB - Once a categorization task has been mastered, if features that once were relevant become irrelevant and features that once were irrelevant become relevant, a decrement in performance-a shift cost-is typically observed. This shift cost may reflect the involvement of two distinguishable factors: the inability to release attention from a previously relevant feature (i.e., attentional perseveration) and/or the inability to re-engage attention to a previously irrelevant feature (i.e., learned irrelevance). Here, we examined the nature of this shift cost in pigeons. We gave four groups of pigeons a categorization task in which we monitored their choice accuracy; at the same time, we tracked the location of their pecks to the relevant and irrelevant attributes of the stimuli to determine to which attributes the birds were attending during the course of learning. After identical training in Phase 1, the roles of the relevant/irrelevant features were changed in Phase 2, so that one group could show only learned irrelevance, a second group could show only attentional perseverance, a third group could show both, and a fourth control group could show neither of these effects. Results disclosed evidence of attentional perseverance, but no evidence of learned irrelevance, either in accuracy or in relevant feature tracking. In addition, we determined that pigeons' allocation of attention to the relevant features followed rather than preceded an increase in choice accuracy. Overall, our findings are best explained by theories which propose that attention is learned and deployed to those features that prove to be reliable predictors of the correct categorization response (e.g., George and Pearce, 2012; Kruschke, 2001; Mackintosh, 1975). PMID- 26548719 TI - Coenzyme Q0 regulates NFkappaB/AP-1 activation and enhances Nrf2 stabilization in attenuation of LPS-induced inflammation and redox imbalance: Evidence from in vitro and in vivo studies. AB - Coenzyme Q (CoQ) analogs with variable number of isoprenoid units have been demonstrated as anti-inflammatory and antioxidant/pro-oxidant molecules. In this study we used CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side chains), a novel quinone derivative, and investigated its molecular actions against LPS-induced inflammation and redox imbalance in murine RAW264.7 macrophages and mice. In LPS-stimulated macrophages, non-cytotoxic concentrations of CoQ0 (2.5-10 MUM) inhibited iNOS/COX-2 protein expressions with subsequent reductions of NO, PGE2, TNF-alpha and IL-1beta secretions. This inhibition was reasoned by suppression of NFkappaB (p65) activation, and inhibition of AP-1 (c Jun., c-Fos, ATF2) translocation. Our findings indicated that IKKalpha-mediated I kappaB degradation and MAPK-signaling are involved in regulation of NFkappaB/AP-1 activation. Furthermore, CoQ0 triggered HO-1 and NQO-1 genes through increased Nrf2 nuclear translocation and Nrf2/ARE-signaling. This phenomenon was confirmed by diminished CoQ0 protective effects in Nrf2 knockdown cells, where LPS-induced NO, PGE2, TNF-alpha and IL-1beta productions remained high. Molecular evidence revealed that CoQ0 enhanced Nrf2 steady-state level at both transcriptional and translational levels. CoQ0-induced Nrf2 activation appears to be regulated by ROS JNK-signaling cascades, as evidenced by suppressed Nrf2 activation upon treatment with pharmacological inhibitors of ROS (N-acetylcysteine) and JNK (SP600125). Besides, oral administration of CoQ0 (5 mg/kg) suppressed LPS-induced (1 mg/kg) induction of iNOS/COX-2 and TNF-alpha/IL-1beta through tight regulation of NFkappaB/Nrf2 signaling in mice liver and spleen. Our findings conclude that pharmacological actions of CoQ0 are mediated via inhibition of NFkappaB/AP-1 activation and induction of Nrf2/ARE-signaling. Owing to its potent anti inflammatory and antioxidant properties, CoQ0 could be a promising candidate to treat inflammatory disorders. PMID- 26548718 TI - The hyaluronic acid inhibitor 4-methylumbelliferone is an NSMase2 activator-role of Ceramide in MU anti-tumor activity. AB - Increased synthesis of hyaluronic acid (HA) is often associated with increased metastatic potential and invasivity of tumor cells. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis, and has been studied as a potential anti-tumor drug to inhibit the growth of primary tumors and distant metastasis of tumor cells. Although several studies reported that the anticancer effects of MU are mediated by inhibition of HA signaling, the mechanism still needs to be clarified. In a previous study we demonstrated the regulation of HA synthesis by ceramide, and now show how MU activated neutral sphingomyelinase2 (NSMase2) generates ceramides and mediates MU induced inhibition of HA synthesis, cell migration and invasion, and apoptosis of tumor cells. Using a HA enriched mouse oligodendroglioma cell line G26-24 we found that MU elevated the activity of NSMase2 and increased ceramide levels, which in turn increased phosphatase PP2A activity. Further, the activated PP2A reduced phosphorylation of Akt, decreased activities of HA synthase2 (HAS2) and calpains, and inhibited both the synthesis of HA, and the migration and invasion of G26-24 tumor cells. In addition, MU mediated ceramide stimulated activation of p53 and caspase-3, reduced SIRT1 expression and decreased G26-24 viability. The mechanism of the MU anticancer therefore initially involves NSMase2/ceramide/PP2A/AKT/HAS2/caspase-3/p53/SIRT1 and the calpain signaling pathway, suggesting that ceramides play a key role in the ability of a tumor to become aggressively metastatic and grow. PMID- 26548720 TI - IL-33 and kidney disease (Review). AB - Interleukin (IL)-33, is a novel member of the IL-1 superfamily, and act as a dual function molecule as a nuclear factor and cytokine. The expression of IL-33 can be detected in several tissues and cells in humans and in mice. In addition to the conventional secretion approach for cytokines, full-length IL-33 can also be released into the extracellular space following cell damage or mechanical injury. IL-33 mediates its biological effects by interacting with the receptors, suppression of tumorigenicity 2 (ST2) and IL-1 receptor accessory protein, activating intracellular molecules in the nuclear factor-kappaB and mitogen activated protein kinase signaling pathways, which drive the production of type 2 cytokines, including IL-4, IL-5 and IL-3, from polarized T helper 2 cells. Increasing evidence indicates that IL-33 is important in chronic kidney disease, and may be involved in the progression of renal fibrosis associated with systemic lupus erythematosus and renal graft damage. In addition, IL-33 contributes to acute kidney injury. In the present review, the biology of IL-33, and the association of IL-33 with kidney diseases are discussed. PMID- 26548721 TI - Genetic and morphological studies of Trichosirocalus species introduced to North America, Australia and New Zealand for the biological control of thistles. AB - Trichosirocalus horridus sensu lato has been used as a biological control agent of several invasive thistles (Carduus spp., Cirsium spp. and Onopordum spp.) since 1974. It has been recognized as a single species until 2002, when it was split into three species based on morphological characters: T. horridus, Trichosirocalus briesei and Trichosirocalus mortadelo, each purported to have different host plants. Because of this taxonomic change, uncertainty exists as to which species were released in various countries; furthermore, there appears to be some exceptions to the purported host plants of some of these species. To resolve these questions, we conducted an integrative taxonomic study of the T. horridus species complex using molecular genetic and morphological analyses of specimens from three continents. Both mitochondrial cytochrome c oxidase subunit I and nuclear elongation factor 1alpha markers clearly indicate that there are only two distinct species, T. horridus and T. briesei. Molecular evidence, morphological analysis and host plant associations support the synonymy of T. horridus (Panzer, 1801) and T. mortadelo Alonso-Zarazaga & Sanchez-Ruiz, 2002. We determine that T. horridus has been established in Canada, USA, New Zealand and Australia and that T. briesei is established in Australia. The former species was collected from Carduus, Cirsium and Onopordum spp. in the field, whereas the latter appears to be specific to Onopordum. PMID- 26548722 TI - Abdominal surgical emergencies in patients with advanced cancer. AB - Abdominal emergency in an advanced oncologic setting is defined as an acute life threatening abdominal pathology in a patient with incurable cancer. These include bowel obstruction, infections and, more rarely, hemorrhage. To benefit the patient, surgery should both increase the survival and improve the quality of life. These two goals are of equal importance and must be achieved together. This is difficult because these patients are frail, often malnourished and have a poor performance status. They also have a high risk of post-operative morbidity and mortality, a major risk of symptom recurrence and a limited life expectancy. For patients near the end-of-life, a therapeutic decision for surgical intervention must respect ethical and legal standards. This review reports the surgical outcomes and median survival of these patients, specifies rules that must be known and respected, and presents non-operative interventional alternatives. PMID- 26548723 TI - Genome sequence of a laccase producing fungus Trametes sp. AH28-2. AB - Trametes sp. AH28-2 (CCTCC AF 2015027) is a white rot fungus isolated from rotting wood in China. Primary study indicated that this strain can be induced by kraft lignin to secrete high levels of extracellular laccase, and differentially express laccase genes upon addition of different phenolic compounds. Here we report the complete genome sequence of Trametes sp. AH28-2 and its genetic basis for lignin degradation and phenolic xenobiotics metabolism. PMID- 26548724 TI - Suppression of nucleosome-binding protein 1 by miR-326 impedes cell proliferation and invasion in non-small cell lung cancer cells. AB - Emerging studies have proposed microRNAs (miRNAs) as novel therapeutic tools for cancer therapy. Nucleosome-binding protein 1 (NSBP1) has been suggested as an oncogene in various types of human cancers. The present study aimed to identify a novel miRNA that could directly target and negatively modulate NSBP1 expression. We found that NSBP1 was highly expressed in non-small cell lung cancer (NSCLC) cells, and knockdown of NSBP1 by NSBP1 small interfering RNA (siRNA) significantly suppressed NSCLC cell proliferation and invasion. Bioinformatics analysis revealed that miR-326 had a putative binding site within the 3' untranslated region of NSBP1. Their substantial relationship was further verified by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and western blot analysis. Overexpression of miR-326 significantly inhibited NSCLC cell proliferation and invasion, which mimicked the effect of NSBP1 siRNA. Furthermore, suppression of NSBP1 by NSBP1 siRNA or miR-326 overexpression remarkably repressed the expression of cyclin B1 and matrix metalloproteinase 9 (MMP9), which are associated with cancer cell proliferation and invasion. Moreover, overexpression of NSBP1 obviously abolished the inhibitory effect of miR-326 on cyclin B1 and MMP9 expression. In addition, an inverse correlation between miR-326 and NSBP1 expression levels was found in NSCLC clinical specimens. Our study demonstrated a direct target relationship between NSBP1 and miR-326 through which miR-326 inhibited cell proliferation and invasion of NSCLC cells. Thus, miR-326-NSBP1 is a promising candidate target for developing novel anticancer therapeutics for NSCLC. PMID- 26548725 TI - Active invadopodia of mesenchymally migrating cancer cells contain both beta and gamma cytoplasmic actin isoforms. AB - Invadopodia are actin-rich protrusions formed by mesenchymally migrating cancer cells. They are mainly composed of actin, actin-associated proteins, integrins and proteins of signaling machineries. These protrusions display focalized proteolytic activity towards the extracellular matrix. It is well known that polymerized (F-)actin is present in these structures, but the nature of the actin isoform has not been studied before. We here show that both cytoplasmic actin isoforms, beta- and gamma-actin, are present in the invadopodia of MDA-MB-231 breast cancer cells cultured on a 2D-surface, where they colocalize with the invadopodial marker cortactin. Invadopodial structures formed by the cells in a 3D-collagen matrix also contain beta- and gamma-actin. We demonstrate this using isoform-specific antibodies and expression of fluorescently-tagged actin isoforms. Additionally, using simultaneous expression of differentially tagged beta- and gamma-actin in cells, we show that the actin isoforms are present together in a single invadopodium. Cells with an increased level of beta- or gamma-actin, display a similar increase in the number and size of invadopodia in comparison to control cells. Moreover, increasing the level of either actin isoforms also increases invasion velocity. PMID- 26548726 TI - Topical lipophilic epigallocatechin-3-gallate on herpes labialis: a phase II clinical trial of AverTeaX formula. AB - OBJECTIVE: Previous in vitro and in vivo studies indicated that catechins from the tea plant (Camellia sinensis) have a therapeutic effect on herpes simplex virus infections. The aim of this study was to clinically evaluate a topical proprietary formulation containing lipophilic catechins (AverTeaX, Camellix, LLC, Evans, GA, USA) on recurrent herpes labialis. STUDY DESIGN: A double-blind, placebo-controlled, randomized trial with 40 participants, initially in two groups. RESULTS: Compared with the vehicle (100% glycerin USP, CVS Pharmacies, Inc., Woonsocket, RI, USA) group, AverTeaX applied topically six to eight times daily resulted in a significant reduction in clinical episode duration (median 4.5 days vs. 9 days; P = .003) and shortened blistering and ulceration stages within an episode from a median of 3 days to 1 day (P = .0003). Median quality-of life scores, based on a multiquestion survey, showed significant differences between the groups with respect to duration of itching, from a median of 4 days to 1 day (P = .0021), and duration until symptom free, from a median of 8 days to 4 days (P = .0016). Significant differences were not found for median scores for itching, pain, burning, swelling, bleeding, and stress. Adverse effects were not reported. CONCLUSION: AverTeaX formulation containing lipophilic catechins effectively inhibited herpes simplex labialis infection with clinical significance. PMID- 26548727 TI - Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study. AB - OBJECTIVE: Sequential postoperative salivary interleukin-6 (IL-6) concentrations were examined in patients with oral squamous cell carcinoma (OSCC) who had early or late locoregional recurrences or those who did not. STUDY DESIGN: Twenty-seven consecutive patients with OSCC were originally included in the study. All patients underwent radical surgery. Four saliva samples were collected before (periods I and II) and after (periods III and IV) surgery, and IL-6 concentrations were measured. RESULTS: Although postoperative (period III: at the time of discharge) salivary IL-6 level was significantly higher in patients with early locoregional recurrence (P = .02) than in those without, no such relationships were observed for preoperative IL-6 concentrations (periods I and II). Postoperative (period IV: 24 months after surgery) IL-6 level was significantly higher in patients with late locoregional recurrence (P = .03) than in those without, but no such relationships were observed for IL-6 concentrations in periods I, II, and III. CONCLUSIONS: Sequential postoperative salivary IL-6 concentration may be a useful marker for diagnosis of early and late locoregional recurrence in OSCC. PMID- 26548728 TI - Three-dimensional evaluation of human jaw bone microarchitecture: correlation between the microarchitectural parameters of cone beam computed tomography and micro-computer tomography. AB - OBJECTIVE: To evaluate the potential feasibility of cone beam computed tomography (CBCT) in the assessment of trabecular bone microarchitecture. STUDY DESIGN: Sixty-eight specimens from four pairs of human jaw were scanned using both micro computed tomography (micro-CT) of 19.37-MUm voxel size and CBCT of 100-MUm voxel size. The correlation of 3-dimensional parameters between CBCT and micro-CT was evaluated. RESULTS: All parameters, except bone-specific surface and trabecular thickness, showed linear correlations between the 2 imaging modalities (P < .05). Among the parameters, bone volume, percent bone volume, trabecular separation, and degree of anisotropy (DA) of CBCT images showed strong correlations with those of micro-CT images. DA showed the strongest correlation (r = 0.693). CONCLUSIONS: Most microarchitectural parameters from CBCT were correlated with those from micro-CT. Some microarchitectural parameters, especially DA, could be used as strong predictors of bone quality in the human jaw. PMID- 26548729 TI - Cone beam computed tomography (CBCT) sialography--an adjunct to salivary gland ultrasonography in the evaluation of recurrent salivary gland swelling. AB - OBJECTIVE: Cone beam computed tomography (CBCT) sialography could help improve the visualization of the ductal system of salivary glands. The aim of this retrospective investigation was to monitor the use of CBCT sialography for the diagnosis of pathologies within the intraglandular ductal system when ultrasonography was inconclusive. STUDY DESIGN: Fourteen consecutive patients suffering from recurrent swelling of a major salivary gland were evaluated. In 12 patients (8 female; 4 male; average age 46 years), a radiopaque contrast agent could be injected into the ductal system, followed by a routine CBCT. Four blinded examiners evaluated the acquired data sets retrospectively. RESULTS: CBCT revealed seven stenosis, two salivary stones, one complete duct atresia, one intraglandular duct ectasia, and one regular duct system. Three of the detected pathologies were strictly intraglandular. CONCLUSIONS: CBCT sialography shows promise as a supplementary noninvasive diagnostic tool for the visualization of the intraglandular ductal system of the major human salivary glands. Controlled studies to further validate this method should be undertaken. PMID- 26548730 TI - Drs. Greene and Obrez's article inaccurate. PMID- 26548731 TI - Response to letters to the editor. PMID- 26548732 TI - Hydroxyurea-induced oral ulceration. AB - Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. PMID- 26548733 TI - Treatment strategies for stage IB cervical cancer: A cost-effectiveness analysis from Korean, Canadian and U.S. perspectives. AB - OBJECTIVES: To assess the cost-effectiveness of two commonly used strategies and an alternative triage strategy for patients with Stage IB cervical cancer in the U.S., Canada, and Korea. METHODS: A Markov state-transition model was constructed to compare three strategies: (1) radical hysterectomy followed by tailored adjuvant therapy (primary surgery), (2) primary chemoradiation, and (3) an MRI based triage strategy, in which patients without risk factors in preoperative MRI undergo primary surgery and those with risk factors undergo primary chemoradiation. All relevant literature was identified to extract the probability data. Cost data were calculated from the perspective of U.S., Canadian, and Korean payers. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Cost-effectiveness ratios were analyzed separately using data from each country. RESULTS: Base case analysis showed that the triage strategy was the most cost-effective of the three strategies in all countries at usual willingness to-pay threshold (Korea: $30,000 per quality-adjusted life year (QALY), Canada and US: $100,000 per QALY). Monte Carlo simulation acceptability curves from Korea indicated that at a willingness-to-pay threshold of $30,000/QALY, triage strategy was the treatment of choice in 71% of simulations. Monte Carlo simulation acceptability curves from US and Canada indicated that at a willingness-to-pay threshold of $100,000/QALY, triage strategy was the treatment of choice in more than half of simulations. CONCLUSIONS: An MRI-based triage strategy was shown to be more cost-effective than primary surgery or primary chemoradiation in the US, Canada, and Korea. PMID- 26548734 TI - The low-FODMAP diet for irritable bowel syndrome: Lights and shadows. AB - Irritable bowel syndrome (IBS) affects 10-15% of the western population. Drug therapy for this entity has shown limited efficacy. The low Fermentable Oligo-, Di-, Monosaccharides And Polyols (FODMAP) diet has recently emerged as an effective intervention for reducing gastrointestinal symptoms in IBS. Currently, several mechanistic studies have proven the rational basis of carbohydrate restriction. In addition, high-quality evidence (prospective studies and randomized controlled trials) from a variety of countries supports the high effectiveness of a low-FODMAP diet for IBS symptoms (70%), especially abdominal bloating, pain, and diarrhea. Importantly, this diet seems to be superior to a gluten-free diet for patients with non-celiac gluten sensitivity. The most controversial features of the low FODMAP diet are its short- and long-term limitations (a high level of restriction, the need for monitoring by an expert dietitian, potential nutritional deficiencies, significant gut microbiota reduction, lack of predictors of response), as well as the potential lack of advantage over alternative dietary, pharmacological and psychological interventions for IBS. Although liberalization of carbohydrate intake is recommended in the long-term, the reintroduction process remains to be clarified as, theoretically, global carbohydrate restriction is deemed to be necessary to avoid additive effects. PMID- 26548735 TI - [Usefulness of systematic chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions]. AB - INTRODUCTION: Premalignant gastric lesions have an increased risk to develop gastric cancer. OBJECTIVE: To evaluate the usefulness of systematic endoscopy that includes chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions. PATIENTS AND METHODS: This longitudinal, prospective study was performed in patients with gastric atrophy, intestinal metaplasia or dysplasia who were referred for endoscopy less than 6 months after the initial diagnosis. The second endoscopy was performed in three phases: phase 1, exhaustive and systematic review of the mucosa with photographic documentation and biopsies of suspicious areas; phase 2, chromoendoscopy with a double dye staining technique using acetic acid 1.2% and indigo carmine 0.5%; phase 3, topographic mapping and random biopsies. RESULTS: A total of 50 patients were included. Nine (18%) had atrophic gastritis, 38 (76%) had intestinal metaplasia, and 3 (6%) had low-grade dysplasia. Systematic endoscopy with chromoendoscopy using a double dye staining technique detected more patients with dysplasia (9 versus 3, p<.05), and a larger number of biopsies with the diagnosis of dysplasia were obtained. This occurred for visible (6 vs. 0, p<.05) and non-visible lesions (6 vs. 3, p=NS). In one patient, initial low grade dysplasia was not detected again in the systematic endoscopy, giving a global endoscopic performance for the detection of lesions of 92%. CONCLUSIONS: Patients with premalignant gastric lesions have synchronous lesions with greater histological severity, which are detected when systematic endoscopy is conducted with indigo carmine dye added to acetic acid. PMID- 26548736 TI - [Right pleural effusion secondary to a pancreaticopleural fistula in a patient with asymptomatic chronic pancreatitis]. PMID- 26548737 TI - A Randomized Pragmatic Clinical Trial of Chiropractic Care for Headaches With and Without a Self-Acupressure Pillow. AB - OBJECTIVE: The purpose of this study was to determine if the addition of a self acupressure pillow (SAP) to typical chiropractic treatment results in significantly greater improvement in tension-type and cervicogenic headache sufferers. METHODS: A pragmatic randomized clinical trial was conducted in a chiropractic college teaching clinic. Thirty-four subjects, including tension type and cervicogenic headache sufferers, 21 to 60 years of age, male or female, completed the study. Group A (n = 15) received typical chiropractic care only (manual therapy and exercises), and group B (n = 19) received typical chiropractic care with daily home use of the SAP. The intervention period was 4 weeks. The main outcome measure was headache frequency. Satisfaction and relief scores were obtained from subjects in the SAP group. Analysis of variance was used to analyze the intergroup comparisons. RESULTS: Owing to failure of randomization to produce group equivalence on weekly headache frequency, analysis of covariance was performed showing a trend (P = .07) favoring the chiropractic only group; however, this was not statistically significant. Group A obtained a 46% reduction of weekly headache frequency (t = 3.1, P = .002; d = 1.22). The number of subjects in group A achieving a reduction in headaches greater than 40% was 71%, while for group B, this was 28%. The mean benefit score (0-3) in group B of the use of the SAP was 1.2 (.86). The mean satisfaction rating of users of the SAP was 10.4 (2.7) out of 15 (63%). CONCLUSION: This study suggests that chiropractic care may reduce frequency of headaches in patients with chronic tension-type and cervicogenic headache. The use of a self-acupressure pillow (Dr Zaxx device) may help those with headache and headache pain relief as well as producing moderately high satisfaction with use. PMID- 26548738 TI - Simple exposure to alcohol cues causally increases negative implicit attitudes toward lesbians and gay men. AB - Previous research has shown that acute alcohol consumption is associated with negative responses toward outgroup members such as sexual minorities. However, simple alcohol cue exposure without actually consuming alcohol also influences social behavior. Hence, it was reasoned that priming participants with words related to alcohol (relative to neutral words) would promote prejudiced attitudes toward sexual minorities. In fact, an experiment showed that alcohol cue exposure causally led to more negative implicit attitudes toward lesbians and gay men. In contrast, participants' explicit attitudes were relatively unaffected by the priming manipulation. Moreover, participants' typical alcohol use was not related to their attitudes toward lesbians and gay men. In sum, it appears that not only acute alcohol consumption but also the simple exposure of alcohol cues may promote negative views toward lesbians and gay men. PMID- 26548739 TI - The publication "Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue" by Enrico Campioli, Tam B. Duong, Francois Deschamps, Vassilios Papadopoulos, Environmental Research 140 (2015), 145-156, merits some critical comments. AB - In essence, the authors report MINCH, a monoester and minor urinary metabolite (Koch et al., 2013) of a plasticizer marketed by BASF under the brandname Hexamoll((r)) DINCH((r)), promotes the differentiation of preadipocytes derived from rat epididymal stromal vascular fraction (SVF) to adipocytes. The authors have over-interpreted their in-vitro data and missed important publicly available in-vivo data. PMID- 26548740 TI - High doses of salicylate reduces glycinergic inhibition in the dorsal cochlear nucleus of the rat. AB - High doses of salicylate induce reversible tinnitus in experimental animals and humans, and is a common tinnitus model. Salicylate probably acts centrally and induces hyperactivity in specific auditory brainstem areas like the dorsal cochlear nucleus (DCN). However, little is known about the effect of high doses of salicylate in synapses and neurons of the DCN. Here we investigated the effects of salicylate on the excitability and evoked and spontaneous neurotransmission in the main neurons (fusiform, cartwheel and tuberculoventral) and synapses of the DCN using whole cell recordings in slices containing the DCN. For this, we incubate the slices for at least 1 h in solution with 1.4 mM salicylate, and recorded action potentials and evoked and spontaneous synaptic currents in fusiform, cartwheel (CW) and putative tuberculoventral (TBV) neurons. We found that incubation with salicylate did not affect the firing of fusiform and TBV neurons, but decreased the spontaneous firing of cartwheel neurons, without affecting AP threshold or complex spikes. Evoked and spontaneous glutamatergic neurotransmission on the fusiform and CW neurons cells was unaffected by salicylate and evoked glycinergic neurotransmission on fusiform neurons was also unchanged by salicylate. On the other hand spontaneous glycinergic transmission on fusiform neurons was reduced in the presence of salicylate. We conclude that high doses of salicylate produces a decreased inhibitor drive on DCN fusiform neurons by reducing the spontaneous firing of cartwheel neurons, but this effect is not able to increase the excitability of fusiform neurons. So, the mechanisms of salicylate-induced tinnitus are probably more complex than simple changes in the neuronal firing and basal synaptic transmission in the DCN. PMID- 26548741 TI - Brain Death in Pediatric Patients in Japan: Diagnosis and Unresolved Issues. AB - Brain death (BD) is a physiological state defined as complete and irreversible loss of brain function. Organ transplantation from a patient with BD is controversial in Japan because there are two classifications of BD: legal BD in which the organs can be donated and general BD in which the organs cannot be donated. The significance of BD in the terminal phase remains in the realm of scientific debate. As indicated by the increasing number of organ transplants from brain-dead donors, certain clinical diagnosis for determining BD in adults is becoming established. However, regardless of whether or not organ transplantation is involved, there are many unresolved issues regarding BD in children. Here, we will discuss the historical background of BD determination in children, pediatric emergencies and BD, and unresolved issues related to pediatric BD. PMID- 26548742 TI - Nomadic genetic elements contribute to oncogenic translocations: Implications in carcinogenesis. AB - Chromosomal translocations as molecular signatures have been reported in various malignancies but, the mechanism behind which is largely unknown. Swapping of chromosomal fragments occurs by induction of double strand breaks (DSBs), most of which were initially assumed de novo. However, decoding of human genome proved that transposable elements (TE) might have profound influence on genome integrity. TEs are highly conserved mobile genetic elements that generate DSBs, subsequently resulting in large chromosomal rearrangements. Previously TE insertions were thought to be harmless, but recently gains attention due to the origin of spectrum of post-insertional genomic alterations and subsequent transcriptional alterations leading to development of deleterious effects mainly carcinogenesis. Though the existing knowledge on the cancer-associated TE dynamics is very primitive, exploration of underlying mechanism promises better therapeutic strategies for cancer. Thus, this review focuses on the prevalence of TE in the genome, associated genomic instability upon transposition activation and impact on tumorigenesis. PMID- 26548744 TI - Design, Synthesis and Structure-Activity Relationship Studies of Novel 4 (1 adamantyl) Phenyl Analogues as HIF-1alpha Inhibitors. AB - Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1alpha. Examination of their structure-activity relationship (SAR) identified the adamantane containing indole derivative 20a as a potent inhibitor of HIF-1alpha in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 uM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis. PMID- 26548743 TI - The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis. AB - Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. PMID- 26548745 TI - Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma. AB - BACKGROUND: The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved. AIMS: To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up. METHODS: Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed. RESULTS: Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%). CONCLUSION: Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma. PMID- 26548746 TI - Higher Rates of Retinopathy of Prematurity after Increasing Oxygen Saturation Targets for Very Preterm Infants: Experience in a Single Center. AB - Randomized trials of oxygen saturation target ranges for extremely preterm infants showed increased survival but increased retinopathy of prematurity with higher compared with lower target ranges. In our center, changing from a target range of 88%-92% to 91%-95% has been associated with increased rates and severity of retinopathy of prematurity. PMID- 26548747 TI - Phenethyl isothiocyanate potentiates anti-tumour effect of doxorubicin through Akt-dependent pathway. AB - The present study aims to investigate the in vivo and in vitro anti-tumour properties of phenethyl isothiocyanate (PEITC) alone and in combination with doxorubicin (Dox). The anti-tumour activity was evaluated in vitro by MTT assay using cultured human breast cancer cell line (MCF-7) and human hepatoma cell line (HepG-2) cell lines. In vivo, Ehrlich solid tumour model was used. Tumour volume, weight and antioxidant parameters were determined. Immunohistochemistry analysis for active (cleaved) caspase-3 was also performed. We tested the effect of PEITC treatment on pAkt/Akt ratio, NF-kappaB p65 DNA binding activity and caspase-9 enzyme activity in both MCF-7 and HepG-2 cell lines. Effect of PEITC treatment on cell migration was assessed by wound healing assay. PEITC and/or Dox treatment significantly inhibited solid tumour volume and tumour weight when compared with control mice. PEITC treatment significantly reduced oxidative stress caused by Dox treatment as indicated by significant increase in total antioxidant capacity and decrease in malondialdehyde level. Microscopic examination of tumour tissues showed a significant increase in active (cleaved) caspase-3 expression in PEITC and/or Dox treated groups. PEITC showed a dose-dependent inhibition of MCF-7 and HepG-2 cellular viability. PEITC inhibited Akt and NF-kappaB activation and increased caspase-9 activity in a dose-dependent manner. PEITC treatment effectively inhibited both MCF-7 and HepG-2 cell migration. We can conclude that PEITC acts via multiple molecular targets to elicit anti-carcinogenic activity. PEITC/Dox combination therapy might be a potential novel strategy, which may benefit patients with breast and liver cancers. PMID- 26548748 TI - Indeterminate Single Thyroid Nodule: Synergistic Impact of Mutational Markers and Sonographic Features in Triaging Patients to Appropriate Surgery. AB - BACKGROUND: Patients labeled as having indeterminate thyroid nodular disease following fine-needle aspiration cytology are at risk of non-optimal initial surgery: an overly radical total thyroidectomy, or an unnecessary two-stage operation. The objective of this study was to assess the impact of combining mutational markers and ultrasonographic (US) features preoperatively on predicting the risk of malignancy in patients with indeterminate nodules, thereby offering them a tailored initial surgical intervention. METHODS: The records of 258 patients who underwent conventional total thyroidectomy for single nodules reported as suspicious for a follicular neoplasm (Bethesda category IV) in a four year period were reviewed. Main issues addressed included: certain US findings (individually and in combination), mutational markers (BRAF and NRAS), and combinations of both. Correlation of these with malignancy was assessed, as was their ability to predict malignancy. The usefulness of combining the absence of suspicious sonographic features and the absence of mutational markers was also evaluated. RESULTS: Among the 258 patients with an indeterminate diagnosis, only 90 lesions were found to be malignant. The sonographic features that correlated significantly with malignancy were irregular margins, microcalcifications, and a "taller than wide" shape. The presence of irregular margins was the feature with the highest positive predictive value. Combinations of two or more features were always associated with predictivity in excess of 90%, and at times at 100%. NRAS mutation was the most common gene alteration. Both BRAF and NRAS mutations were mutually exclusive and correlated significantly with malignancy. Their predictivity of malignancy was high, particularly when combined with suspicious sonographic features (100%). The major limitation of both suspicious sonographic features and/or mutational markers was their low occurrence in malignancy. The absence of both mutational markers and suspicious sonographic features proved extremely useful in tailoring surgical strategy, as it could have ultimately spared 143/258 patients (55%) an overly radical thyroidectomy. CONCLUSION: The preoperative utility of mutational markers and sonographic features in combination has a synergistic impact. It can predict the risk of malignancy with high accuracy, properly triaging patients to appropriate surgery. PMID- 26548749 TI - Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution. AB - Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16-0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versus C/T [p = 0.033; OR: 2.03(1.00-4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00-3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58 13.06)], [p = 0.001; OR: 3.49(1.44-8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87-16.29)], [p = 0.007; OR: 5.21(1.65-16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22-7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide. PMID- 26548750 TI - Autoimmune regulator-overexpressing dendritic cells induce T helper 1 and T helper 17 cells by upregulating cytokine expression. AB - The autoimmune regulator (Aire) protein is a transcriptional activator that is essential in central immune tolerance, as it regulates the ectopic expression of many tissue-restricted antigens in medullary thymic epithelial cells. Aire expression has also been described in hematopoietic cells, such as monocytes/macrophages and dendritic cells (DCs), in the peripheral immune system. However, the role of Aire expression in peripheral immune system cells, including DCs, remains to be elucidated. In the present study, the effects of secreted cytokines from Aire-overexpressing DCs on cluster of differentiation (CD)4+ T cell subsets were investigated. The dendritic cell line, DC2.4, which overexpresses Aire, was co-cultured with CD4+ T cells from splenocytes using Transwell inserts. The results indicate that Aire-overexpressing cells induce T helper (Th)1 subsets by increasing interleukin (IL)-12 expression, and induce Th17 subsets by upregulating IL-6 and transforming growth factor (TGF)-beta production. In addition, it was observed that increased levels of phosphorylated extracellular signal-regulated kinases and p38 upregulated the expression of cytokines in Aire-overexpressing cells. These data suggest that Aire may have a role in inducing Th1 and Th17 differentiation by upregulating cytokine expression in DCs. PMID- 26548751 TI - The prevalence of injury in Kendo. AB - OBJECTIVE: Kendo is a Japanese martial art analogous to fencing, which is becoming increasingly popular worldwide. The large number of participants creates a need to assess injury patterns to better train them. The purpose of this study is to describe current injury rates in kendo and compare these rates to other martial arts. METHODS: This retrospective study used an online questionnaire sent to 500 active members of the All United States Kendo Federation and World Kendo Federation. The questionnaire, based on the NCAA Injury Surveillance System, contains questions regarding location and type of injuries sustained during competition and practice, time lost to training, and competitor demographics. Statistical analyses between competitor demographics and injury rates are provided. Injury rates are expressed as injury rates/minute of competition or practice and by athlete exposures. 95% CIs were calculated. RESULTS: Responses from 307 of 500 kendo players were received (response rate = 61.4%). 41 (18%) male and 13 (16%) female participants reported injury to only one body region, while 16 (7%) men and one (1%) woman reported no injuries. 166 (74%) males and 70 (83%) females reported injuries to two or more body regions. The most common sites of injury involved the foot/ankle (65.1%), wrist/hand (53.5%) and elbow/forearm (48.8%). Most injuries occurred during practice (87.9% foot/ankle, 89.9% wrist/hand, elbow/forearm 92.2%). The most common injuries were contusions, abrasions, and sprains/strains. Injury rates were 121/1000 A-E (0.025 injuries/min) in tournaments versus 20.5/1000 A-E (0.011 injuries/min) in training. 26% of injuries resulted in time off of participation, with an average recovery time of 15 days (range = 1 day-1 year). CONCLUSIONS: Although more total injuries occurred in practice than in competition, there was a lower injury rate in kendo than in taekwondo and western-style fencing. This study demonstrates that kendo is a relatively safe sport compared to other martial arts sports. PMID- 26548752 TI - Biomarkers of drug-induced acute kidney injury in the adult. AB - INTRODUCTION: This article addresses general biomarkers of drug-induced acute kidney injury (AKI) and their application in development and progression of AKI in the adult. It also highlights some clinical benefits, but also uncertainties, of biomarker use. AREAS COVERED: Drug-induced AKI is traditionally diagnosed by monitoring serum creatinine (SCr), blood urea nitrogen and albuminuria. The sensitivity of these measures is, however, limited to well-established AKI. Application of selected biomarkers for early diagnosis of drug-induced AKI may inform on progression of AKI and alert clinicians to adopt renoprotective strategies at the earliest times. Novel biomarkers, accepted for early detection of drug-induced AKI (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-beta-d-glucosaminidase), may be useful additions in panels of biomarkers. Clinical biomarkers of cell cycle arrest, tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 show promise but need further validation in clinical trials. EXPERT OPINION: Traditional parameters, such as SCr, provide some guidance for functional decline in drug induced AKI but early, more sensitive, affordable, clinically acceptable, biomarkers of kidney dysfunction are needed. Basic biological understanding of AKI will improve with high-throughput methodologies such as proteomics and metabolomics, and this should lead to identification and usage of novel biomarkers. Ultimately, a combination of biomarkers indicating kidney dysfunction and damage is likely to be required. PMID- 26548753 TI - Reporting health care decision models: a prospective reliability study of a multidimensional evaluation framework. AB - The aim of this study was to evaluate the inter-rater reliability of the Phillips checklist, a proposed framework for the quality assessment of modeling studies. Six raters evaluated nine modeling studies from three different medical specialties. Intra-class correlation (ICC) and corresponding variance components were estimated from these studies. Raters were asked to comment on their experience with the framework. While overall the mean inter-rater reliability showed no significant rater-effect (ICC = 0.69, p = 0.064), there was - presumably as a result of a lower study variability - a significant rater effect for clopidogrel only (p < 0.001). The framework allowed a more structured methodological assessment but several items remained unclear. Regarding the quality assessment of modeling studies with the proposed framework, the rater variability is similar or even higher than variability because of studies or residual effects. Several scoring items can and should be improved to ease interpretation. PMID- 26548754 TI - Suicide and aging: special issue of Aging & Mental Health. PMID- 26548755 TI - Pacifier Use, Finger Sucking, and Infant Sleep. AB - Few studies to date have investigated the relationship between pacifier use or finger sucking and infant sleep. One hundred and four mothers of infants (ages 0 11 months) completed the Brief Infant Sleep Questionnaire (BISQ). Infants who engaged in finger sucking had fewer night wakings and longer stretches of nighttime sleep, although less daytime sleep. There were no significant differences in sleep patterns between pacifier users and infants who did not engage in nonnutritive sucking. Furthermore, no significant differences were found across groups for sleep ecology, including parental involvement at bedtime and following night wakings. Finally, infants were consistently able to retrieve their pacifiers independently by 7 months of age, although this did not appear to be associated with sleep outcomes. Results suggest that when parents are deciding whether to give their infant a pacifier, sleep may not be a critical factor. In contrast, parents of finger and thumb suckers should be reassured that this nonnutritive sucking is beneficial to sleep, at least in the first year of life. PMID- 26548757 TI - Is there a Place for Bevacizumab in Patients with Extensive-Stage Small Cell Lung Cancer? AB - It was estimated that small cell lung cancer (SCLC) accounts for about one Sixth of all lung cancer cases. Patients with SCLC are usually diagnosed in advanced stage of disease. Unfortunately at this stage, prognosis is very poor. Bevacizumab is a monoclonal antibody against VEGF, which inhibits the angiogenesis in malignant tumors. Although Bevacizumab has been approved for firstline use in advanced non-SCLC, the first report has been available for its use in SCLC. In this review, we summarized all available data on the use of Bev in SCLC patients. Finally, future directions are discussed. PMID- 26548756 TI - Cultural traditions across a migratory network shape the genetic structure of southern right whales around Australia and New Zealand. AB - Fidelity to migratory destinations is an important driver of connectivity in marine and avian species. Here we assess the role of maternally directed learning of migratory habitats, or migratory culture, on the population structure of the endangered Australian and New Zealand southern right whale. Using DNA profiles, comprising mitochondrial DNA (mtDNA) haplotypes (500 bp), microsatellite genotypes (17 loci) and sex from 128 individually-identified whales, we find significant differentiation among winter calving grounds based on both mtDNA haplotype (FST = 0.048, PhiST = 0.109, p < 0.01) and microsatellite allele frequencies (FST = 0.008, p < 0.01), consistent with long-term fidelity to calving areas. However, most genetic comparisons of calving grounds and migratory corridors were not significant, supporting the idea that whales from different calving grounds mix in migratory corridors. Furthermore, we find a significant relationship between delta(13)C stable isotope profiles of 66 Australian southern right whales, a proxy for feeding ground location, and both mtDNA haplotypes and kinship inferred from microsatellite-based estimators of relatedness. This indicates migratory culture may influence genetic structure on feeding grounds. This fidelity to migratory destinations is likely to influence population recovery, as long-term estimates of historical abundance derived from estimates of genetic diversity indicate the South Pacific calving grounds remain at <10% of pre-whaling abundance. PMID- 26548758 TI - Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer. AB - Among the various drug delivery devices, nanoliposome is an emerging formulation in the treatment of cancer. Here we have developed tamoxifen citrate (TC) loaded nanoliposome conjugated with phosphoethanolamine (PE) by thin film hydration method. Various physicochemical and biopharmaceutical characterization studies such as drug-excipients interaction, surface morphology, energy dispersive X-ray analysis, zeta potential, in vitro drug release, cellular uptake, in vitro cytotoxicity assay and in vivo pharmacokinetic profiles were conducted. TC-loaded nanoliposome (TNL1) and PE-conjugated TC-loaded nanoliposome (TNL-PE) showed 3.23+/-0.26% and 3.07+/-0.05% drug loading values, respectively. Average diameters (z-average) of the nanoliposomes were within 100 nm, with negative zeta potentials and cumulative percentages of drug release were 75.77+/-12.21% and 61.04+/-10.53% at 30 h for TNL1 and TNL-PE respectively. Predominant uptake of both the types of nanoliposomes was visualized in MCF-7 breast cancer cells. TNL1 and TNL-PE decreased the cell viability from 95.95+/-0.37 to 12.22+/-0.64% and from 96.51+/-0.24 to 13.49+/-0.08% respectively. In vivo pharmacokinetic study showed that AUC 0-infinity, AUMC0-infinity, MRT, and t1/2 value of TNL-PE increased (22%, 100%, 2.66 fold and 60% respectively) as compared to the free drug. Administration of TNL-PE decreased the renal clearance value (about 38%) as compared to the free drug. TNL1 and TNL-PE released the drug in a sustained manner. Further, TNL-PE may be used for active targeting for breast cancer cells when it is tagged with specific antibodies to PE, a linker molecule. PMID- 26548759 TI - Targeting ABCB1 and ABCC1 with their Specific Inhibitor CBT-1(r) can Overcome Drug Resistance in Osteosarcoma. AB - Clinical treatment response achievable with conventional chemotherapy in high grade osteosarcoma (OS) is severely limited by the presence of intrinsic or acquired drug resistance, which in previous studies has been mainly addressed for overexpression of ABCB1 (MDR1/P-glycoprotein). This study was aimed to estimate the impact on OS drug resistance of a group of ATP binding cassette (ABC) transporters, which in other human tumors have been associated with unresponsiveness to the drugs that represent the backbone of multidrug treatment regimens for OS (doxorubicin, methotrexate, cisplatin). By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CBT-1((r)) (Tetrandrine, NSC-77037). We found that in our OS cell lines this agent was able to revert the ABCB1/ABCC1-mediated resistance against doxorubicin, as well as against the drugs used in second-line OS treatments that are substrates of these transporters (taxotere, etoposide, vinorelbine). Our findings indicated that inhibiting ABCB1 and ABCC1 with CBT-1((r)), used in association with conventional chemotherapeutic drugs, may become an interesting new therapeutic option for unresponsive or relapsed OS patients. PMID- 26548761 TI - Circulating phagocytes: the ancient and conserved interface between immune and neuroendocrine function. AB - Immune and neuroendocrine functions display significant overlap in highly divergent and evolutionarily distant models such as molluscs, crustaceans, insects and mammals. Fundamental players in this crosstalk are professional phagocytes: macrophages in vertebrates and immunocytes in invertebrates. Although they have different developmental origins, macrophages and immunocytes possess comparable functions and differentiate under the control of evolutionarily conserved transcription factors. Macrophages and immunocytes share their pools of receptors, signalling molecules and pathways with neural cells and the neuro endocrine system. In crustaceans, adult transdifferentiation of circulating haemocytes into neural cells has been documented recently. In light of developmental, molecular and functional evidence, we propose that the immune neuroendocrine role of circulating phagocytes pre-dates the split of protostomian and deuterostomian superphyla and has been conserved during the evolution of the main groups of metazoans. PMID- 26548760 TI - Biological and immunotoxicity evaluation of antimicrobial peptide-loaded coatings using a layer-by-layer process on titanium. AB - The prevention and control of peri-implantitis is a challenge in dental implant surgery. Dental implants with sustained antimicrobial coating are an ideal way of preventing peri-implantitis. This study reports development of a non- immunotoxicity multilayered coating on a titanium surface that had sustained antimicrobial activity and limited early biofilm formation. In this study, the broad spectrum AMP, Tet213, was linked to collagen IV through sulfo-SMPB and has been renamed as AMPCol. The multilayer AMPCol coatings were assembled on smooth titanium surfaces using a LBL technique. Using XPS, AFM, contact angle analysis, and QCM, layer-by-layer accumulation of coating thickness was measured and increased surface wetting compared to controls was confirmed. Non-cytotoxicity to HaCaT and low erythrocyte hemolysis by the AMPCol coatings was observed. In vivo immunotoxicity assays showed IP administration of AMPCol did not effect serum immunoglobulin levels. This coating with controlled release of AMP decreased the growth of both a Gram-positive aerobe (Staphylococcus aureus) and a Gram-negative anaerobe (Porphyromonas gingivalis) up to one month. Early S. aureus biofilm formation was inhibited by the coating. The excellent long-term sustained antimicrobial activity of this multilayer coating is a potential method for preventing peri-implantitis through coated on the neck of implants before surgery. PMID- 26548762 TI - First Occurrence of a Furano-glycyrrhetinoate and Its Cytotoxicity. AB - (18alpha)-Glycyrrhetinic acid (4) was prepared from (18beta)-glycyrrhetinic acid (1), and the cytotoxicity of some derivatives was investigated by photometric SRB assays employing several human tumor cell lines. In summary, (18beta)-1 is slightly more cytotoxic than its (18alpha) epimer 4, but its cytotoxicity is negligible. Higher cytotoxicity was observed for the esters 2 and 5 and for the 3 O-acetylated esters 3 and 6. Cytotoxicity was improved dramatically when the hydroxyl group at position C-3 was replaced by an amino moiety. SeO2 oxidations gave access to a novel furano-glycyrrhetinoate 15. Interestingly, its seleno analog 16 is approximately five to six times less cytotoxic for the tumor cell lines tested, and tumor/non-tumor selectivity is lost upon replacement of the oxygen by a selenium substituent. PMID- 26548764 TI - Neuropsychopharmacology: Reflections on 40 Volumes. PMID- 26548763 TI - Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice. AB - Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. Lastly, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior. PMID- 26548765 TI - Albert Sjoerdsma. PMID- 26548766 TI - Proteomics of the red blood cell carbonylome during blood banking of erythrocyte concentrates. AB - PURPOSE: Transfusion of red blood cells (RBCs) is a daily medical procedure. Erythrocyte concentrates (ECs) can be stored up to 56 days at 4 degrees C in saline additive solution mainly composed of adenine and sugar. Such nonphysiological conditions induce the occurrence of storage lesions, such as alterations of metabolism, protein oxidation, and deterioration of rheological properties. Their accumulation tends to decrease the main EC therapeutic property, that is, the oxygenation capacity. Protein carbonylation is a marker of oxidative stress and aging, and its occurrence during RBC storage was earlier characterized as a time-dependent and cellular compartment dependent modification. EXPERIMENTAL DESIGN: Three ECs from independent donations were followed. The carbolynome was here characterized in soluble and membrane extracts (n-dodecyl beta-D-maltoside-based extraction buffer) of RBCs stored for 6, 27, and 41 days, through biotin hydrazide derivatization, biotin-avidin affinity purification, SDS-PAGE separation, and LC-MS/MS analyses. RESULTS: A total of 142 and 20 proteins were identified as carbonylated in soluble and membrane extracts, respectively. Particularly, a time-dependent evolution of 26.8% of the soluble carbonylome was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Affected cellular mechanisms involve antioxidant defenses, metabolism pathways, and proteasomal degradation. To better store RBCs those functions have to be preserved, which opens new routes of investigation in transfusion medicine. PMID- 26548767 TI - HIV psychiatry in the era of combined antiretroviral therapy: top five issues. PMID- 26548768 TI - Cu-Based Nanocomposites as Multifunctional Catalysts. AB - Herein, we report the synthesis of Cu/Cu2 O nanocomposites by a one-step hydrothermal process at 180 degrees C, for which the resulting morphology is dependent on the hydrothermal reaction time (24, 72, and 120 h). With a longer reaction time of 120 h, a rod-shape morphology is obtained, whereas at 72 and 24 h assemblies of nanoparticles are obtained. The rod-shaped (120 h) particles of the Cu/Cu2 O nanocomposites show a much higher efficiency (6.3 times) than the agglomerates and 2.5 times more than the assemblies of nanoparticles for the hydrogen-evolution reaction. During the oxygen-evolution reaction, the nanorods produce a current that is 5.2 and 3.7 times higher than that produced by the agglomerated and assembled nanoparticles, respectively. The electrocatalysts are shown to be highly stable for over 50 cycles. As catalysts for organic synthesis, a 100 % yield is achieved in the Sonogashira cross-coupling reaction with the nanorods, which is higher than with the other nanocomposite particles. This result demonstrates the significant enhancement of yield obtained with the nanorods for cross-coupling reactions. PMID- 26548770 TI - Analysis of microRNA and gene networks in human chronic myelogenous leukemia. AB - Molecular biologists have identified a number of genes and microRNAs (miRs) associated with chronic myelogenous leukemia (CML). However, their underlying mechanisms in CML remain unclear. In the present study, three regulatory networks of genes and miRs were constructed to elucidate the underlying mechanisms of CML. The first network was the experimentally validated network of miRs and genes. The second was the dysregulatory network of CML, consisting of dysregulated genes and miRs, contributing to the pathogenesis of CML. The third was the CML-associated network, consisting of CML-associated genes and miRs. In addition to dysregulated genes and miRs, the associated network includes non-dysregulated genes and miRs that contribute to prevention, diagnosis, metastasis and therapy of CML. Key pathways were extracted and compared to distinguish the similarities and differences between dysregulatory nodes among the three networks. V-myb avian myeloblastosis viral oncogene homolog and miR-155 were observed to form a feedback loop module in the dysregulatory network. Regulation of the dysregulatory network may present as a strategy for gene therapy of CML. The current study provides an improved understanding of the molecular mechanisms of, and a potential treatment strategy for, CML. PMID- 26548771 TI - A novel approach of high speed scratching on silicon wafers at nanoscale depths of cut. AB - In this study, a novel approach of high speed scratching is carried out on silicon (Si) wafers at nanoscale depths of cut to investigate the fundamental mechanisms in wafering of solar cells. The scratching is conducted on a Si wafer of 150 mm diameter with an ultraprecision grinder at a speed of 8.4 to 15 m/s. Single-point diamonds of a tip radius of 174, 324, and 786 nm, respectively, are used in the study. The study finds that at the onset of chip formation, an amorphous layer is formed at the topmost of the residual scratch, followed by the pristine crystalline lattice beneath. This is different from the previous findings in low speed scratching and high speed grinding, in which there is an amorphous layer at the top and a damaged layer underneath. The final width and depth of the residual scratch at the onset of chip formation measured vary from 288 to 316 nm, and from 49 to 62 nm, respectively. High pressure phases are absent from the scratch at the onset of either chip or crack formation. PMID- 26548772 TI - On the Triple Role of Fluoride Ions in Palladium-Catalyzed Stille Reactions. AB - The mechanism of Stille reactions (cross-coupling of ArX with Ar'SnnBu3 ) performed in the presence of fluoride ions is established. A triple role for fluoride ions is identified from kinetic data on the rate of the reactions of trans-[ArPdBr(PPh3 )2 ] (Ar=Ph, p-(CN)C6 H4 ) with Ar'SnBu3 (Ar'=2-thiophenyl) in the presence of fluoride ions. Fluoride ions promote the rate-determining transmetallation by formation of trans-[ArPdF(PPh3 )2 ], which reacts with Ar'SnBu3 (Ar'=Ph, 2-thiophenyl) at room temperature, in contrast to trans [ArPdBr(PPh3 )2 ], which is unreactive. However, the concentration ratio [F(-) ]/[Ar'SnBu3 ] must not be too high, because of the formation of unreactive anionic stannate [Ar'Sn(F)Bu3 ](-) . This rationalises the two kinetically antagonistic roles exerted by the fluoride ions that are observed experimentally, and is found to be in agreement with the kinetic law. In addition, fluoride ions promote reductive elimination from trans-[ArPdAr'(PPh3 )2 ] generated in the transmetallation step. PMID- 26548773 TI - Functional ionic liquids for enhancement of Li-ion transfer: the effect of cation structure on the charge-discharge performance of the Li4Ti5O12 electrode. AB - As the development of high energy-density Li-ion batteries moves ahead, ensuring safety of the batteries has become increasingly important. Among the unique physicochemical properties of ionic liquids, thermal stability can be one of the answers to the challenge. The use of ionic liquids, however, causes critical issues concerning the kinetics of Li-ion transfer at the electrode-electrolyte interface. In the present study, ionic liquids consisting of 1-((2 methoxyethoxy)methyl)-1-methylpiperidinium (PP1MEM) or 1-hexyl-1 methylpiperidinium (PP16) and bis(trifluoromethanesulfonyl)amide (TFSA) were applied to an electrolyte for Li-ion batteries, and we investigated the effect of cation structure on interfacial Li-ion transfer using Li4Ti5O12 as a model electrode by means of Raman spectroscopy and electrochemical impedance spectroscopy. It was found that the ether functional group in the PP1MEM cation has the meaningful function; the cation structure reduces the electrostatic interaction between the Li ion and TFSA anions in an ionic liquid electrolyte. The solvation number of the TFSA anion per Li ion consequently became smaller than that in PP16-TFSA, and the lower solvation number in PP1MEM-TFSA allowed the facile Li-ion diffusion in the electrolyte bulk rather than the interfacial Li ion transfer and significantly improved the rate performance. The results offer the prospect of utilization of PP1MEM-TFSA as an electrolyte solvent. The knowledge obtained from this study contributes to the development of next generation Li-ion batteries having both high energy density and high safety. PMID- 26548774 TI - Liposome chaperon in cell-free membrane protein synthesis: one-step preparation of KcsA-integrated liposomes and electrophysiological analysis by the planar bilayer method. AB - Chaperoning functions of liposomes were investigated using cell-free membrane protein synthesis. KcsA potassium channel-reconstituted liposomes were prepared directly using cell-free protein synthesis. In the absence of liposomes, all synthesized KcsA protein aggregated. In the presence of liposomes, however, synthesized KcsA spontaneously integrated into the liposome membrane. The KscA reconstituted liposomes were transferred to the planar bilayer across a small hole in a thin plastic sheet and the channel function of KcsA was examined. The original electrophysiological activities, such as voltage- and pH-dependence, were observed. These results suggested that in cell-free membrane protein synthesis, liposomes act as chaperones, preventing aggregation and assisting in folding and tetrameric formation, thereby allowing full channel activity. PMID- 26548775 TI - Bacterial cytoskeleton and implications for new antibiotic targets. AB - Traditionally eukaryotes exclusive cytoskeleton has been found in bacteria and other prokaryotes. FtsZ, MreB and CreS are bacterial counterpart of eukaryotic tubulin, actin filaments and intermediate filaments, respectively. FtsZ can assemble to a Z-ring at the cell division site, regulate bacterial cell division; MreB can form helical structure, and involve in maintaining cell shape, regulating chromosome segregation; CreS, found in Caulobacter crescentus (C. crescentus), can form curve or helical filaments in intracellular membrane. CreS is crucial for cell morphology maintenance. There are also some prokaryotic unique cytoskeleton components playing crucial roles in cell division, chromosome segregation and cell morphology. The cytoskeleton components of Mycobacterium tuberculosis (M. tuberculosis), together with their dynamics during exposure to antibiotics are summarized in this article to provide insights into the unique organization of this formidable pathogen and druggable targets for new antibiotics. PMID- 26548776 TI - Using the inherent chemistry of the endothelin-1 peptide to develop a rapid assay for pre-transplant donor lung assessment. AB - Endothelin-1 is a potent vasoconstrictive peptide that plays an important role in ex vivo lung perfusion. ET-1 expression levels are predictive of lung transplant outcomes and represent a valuable monitoring tool for surgeons; however, traditional techniques that measure [ET-1] are not suitable for the transplant setting. Herein, we demonstrate a new assay that rapidly measures ET-1 peptide levels in lung perfusate. PMID- 26548777 TI - Validation of a Finite Element Humeroradial Joint Model of Contact Pressure Using Fuji Pressure Sensitive Film. AB - A finite element (FE) elbow model was developed to predict the contact stress and contact area of the native humeroradial joint. The model was validated using Fuji pressure sensitive film with cadaveric elbows for which axial loads of 50, 100, and 200 N were applied through the radial head. Maximum contact stresses ranged from 1.7 to 4.32 MPa by FE predictions and from 1.34 to 3.84 MPa by pressure sensitive film measurement while contact areas extended from 39.33 to 77.86 mm2 and 29.73 to 83.34 mm2 by FE prediction and experimental measurement, respectively. Measurements from cadaveric testing and FE predictions showed the same patterns in both the maximum contact stress and contact area, as another demonstration of agreement. While measured contact pressures and contact areas validated the FE predictions, computed maximum stresses and contact area tended to overestimate the maximum contact stress and contact area. PMID- 26548778 TI - Impact of Variety and Agronomic Factors on Crude Protein and Total Lysine in Chicory; N(epsilon)-Carboxymethyl-lysine-Forming Potential during Drying and Roasting. AB - During the heat treatment of coffee and its substitutes some compounds potentially deleterious to health are synthesized by the Maillard reaction. Among these, N(epsilon)-carboxymethyl-lysine (CML) was detected at high levels in coffee substitutes. The objective of this study was to evaluate the impact of changes in agricultural practice on the lysine content present in chicory roots and try to limit CML formation during roasting. Of the 24 varieties analyzed, small variations in lysine content were observed, 213 +/- 8 mg/100 g dry matter (DM). The formation of lysine tested in five commercial varieties was affected by the nitrogen treatment with mean levels of 176 +/- 2 mg/100 g DM when no fertilizer was added and 217 +/- 7 mg/100 g DM with a nitrogen supply of 120 kg/ha. The lysine content of fresh roots was significantly correlated to the concentration of CML formed in roasted roots (r = 0.51; p < 0.0001; n = 76). PMID- 26548779 TI - Acid/base controllable complexation of a triptycene-derived macrotricyclic host and protonated 4,4'-bipyridinium/pyridinium salts. AB - A new acid/base controllable host-guest system based on a triptycene-derived macrotricyclic host and protonated 4,4'-bipyridinium/pyridinium salts was developed. Moreover, the competition complexation process between the host and two different kinds of 4,4'-bipyridinium salts could also be chemically controlled by acid and base. PMID- 26548782 TI - Investigating Community Concerns Regarding HIV Prevention Organizations' Expertise in Serving HIV-Vulnerable Populations. AB - BACKGROUND: People living with human immunodeficiency virus (HIV)/AIDS (PLWH/A) and others affected have expressed that cultural differences between patients and providers can create barriers to care and prevention. These barriers are exacerbated in the case of vulnerable populations who are often marginalized by society. During the formative phase of a community-based participatory research (CBPR) process, the researchers' community advisory committee (CAC) and HIV stakeholders shared anecdotes of incongruencies between needs of HIV-vulnerable populations and expertise of local providers. In response, researchers worked with the CAC to develop survey questions intended for providers of HIV prevention services in a region afflicted with some of the highest HIV prevalence rates in the country. OBJECTIVE: The objective of this study was to identify and validate HIV stakeholders' perceptions about challenges to provision of HIV services through a sequential mixed methods study design. METHODS: Thirty HIV prevention organizations (HPOs) were identified as local leaders in HIV prevention by community stakeholders and through community event attendance. Each HPO was invited to participate in an interviewer-assisted survey examining population specific expertise and service for 15 HIV-vulnerable populations. Frequency analysis was used to compare HPOs' expertise relative to who they serve (n = 26). RESULTS: Although 13 of the HIV-vulnerable populations were served by more than 50% of the HPOs, only 2 of these 13 populations were served with high expertise by more than one half of the HPOs in the sample. CONCLUSION: These data give credence to the CAC's concern regarding misalliance between whom HPOs serve and with whom they have high expertise, a factor potentially influencing HIV outcomes among HIV-vulnerable populations. PMID- 26548780 TI - TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres. AB - KEY POINTS: The transient receptor potential melastatin 4 (TRPM4) inhibitor 9 phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. ABSTRACT: Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9 phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1*10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9 phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 +/- 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. PMID- 26548783 TI - The Chilcapamba-McGill Partnership: Exploring Access to Maternal and Newborn Care in Indigenous Communities of Ecuador. AB - BACKGROUND: Based on a participatory research (PR) partnership between Family Medicine at McGill University, Canada and the Andean community of Chilcapamba, Ecuador, a medical student study focused on maternal and newborn health. OBJECTIVES: To evaluate the access to maternal and newborn care and the occurrence of intrafamilial violence in women with children 5 years of age or less in three indigenous communities of Ecuador. METHODS: A semistructured survey explored the perinatal and intrapartum care as well as intrafamilial violence. RESULTS: All women (N = 30) received prenatal care, 29 received postnatal care from a physician and 77% gave birth at the hospital. Eighty percent of women experienced intrafamilial violence; 73% reported psychological and 53% physical violence. CONCLUSIONS: There is good access to maternal and newborn health care, although the reported level of violence is high. Results were shared with the community and will be used in a local community health worker (CHW) training program. Our project highlights the importance of PR to investigate sensitive health challenges. PMID- 26548784 TI - Vision Voice: A Multimedia Exploration of Diabetes and Vision Loss in East Harlem. AB - BACKGROUND: East Harlem, New York, is a community actively struggling with diabetes and its complications, including vision-related conditions that can affect many aspects of daily life. OBJECTIVES: Vision Voice was a qualitative community-based participatory research (CBPR) study that intended to better understand the needs and experiences of people living with diabetes, other comorbid chronic illnesses, and vision loss in East Harlem. METHODS: Using photovoice methodology, four participants took photographs, convened to review their photographs, and determined overarching themes for the group's collective body of work. LESSONS LEARNED: Identified themes included effect of decreased vision function on personal independence/mobility and self-management of chronic conditions and the importance of informing community members and health care providers about these issues. The team next created a documentary film that further develops the narratives of the photovoice participants. CONCLUSIONS: The Vision Voice photovoice project was an effective tool to assess community needs, educate and raise awareness. PMID- 26548786 TI - A Community-Based Participatory Research Approach for Preventing Childhood Obesity: The Communities and Schools Together Project. AB - BACKGROUND: Childhood obesity is a systemic and complex, multilevel public health problem. Research approaches are needed that effectively engage communities in reversing environmental determinants of child obesity. OBJECTIVES: This article discusses the Communities and Schools Together (CAST) Project and lessons learned about the project's community-based participatory research (CBPR) model. METHODS: A partnership of schools, community organizations, and researchers used multiple methods to examine environmental health risks for childhood obesity and conduct school-community health programs. Action work groups structured partner involvement for designing and implementing study phases. LESSONS LEARNED: CBPR in child obesity prevention involves engaging multiple communities with overlapping yet divergent goals. Schools are naturally situated to participate in child obesity projects, but engagement of key personnel is essential for functional partnerships. Complex societal problems require CBPR approaches that can align diverse communities and necessitate significant coordination by researchers. CBPR can provide simultaneous health promotion across multiple communities in childhood obesity prevention initiatives. Support for emergent partner activities is an essential practice for maintaining community interest and involvement in multiyear CBPR projects. CONCLUSION: Investigator-initiated CBPR partnerships can effectively organize and facilitate large, health-promoting partnerships involving multiple, diverse stakeholder communities. Lessons learned from CAST illustrate the synergy that can propel projects that are holistically linked to the agents of a community. PMID- 26548787 TI - Lessons Learned: A Strategic Alliance to Improve Elementary Physical Education in an Urban School District. AB - BACKGROUND: Physical education (PE) can help to achieve important public health goals, but is often under-prioritized and lacking in schools. OBJECTIVES: To detail the actions, impact, and successes of a strategic alliance formed by three collaborating organizations to improve PE in a large California school district. METHODS: Semistructured interviews with alliance members, principals, and teachers in 20 elementary schools, 3 years after the alliance formation. LESSONS LEARNED: Interviewees reported district-level increases in priority and funding for PE and attributed improvements to the alliance's collection and dissemination of local data on the status of PE. Common goals, trust, and open communication within the alliance were seen as critical to the alliance's success. However, changes in district- or school-level accountability measures for PE were not reported. CONCLUSIONS: This strategic alliance succeeded in promoting district level priority and funding for PE. Ongoing alliance work will focus on increasing accountability measures for PE, which may take longer to implement. PMID- 26548788 TI - Pregnancy and Parenting Support for Incarcerated Women: Lessons Learned. AB - BACKGROUND: There are more than 200,000 incarcerated women in U.S. prisons and jails, and it is estimated that 6% to 10% are pregnant. Pregnant incarcerated women experience complex risks that can compromise their health and the health of their offspring. OBJECTIVES: Identify lessons learned from a community-university pilot study of a prison-based pregnancy and parenting support program. METHODS: A community-university-corrections partnership was formed to provide education and support to pregnant incarcerated women through a prison-based pilot program. Evaluation data assessed women's physical and mental health concerns and satisfaction with the program. Between October 2011 and December 2012, 48 women participated. LESSONS LEARNED: We learned that providing services for pregnant incarcerated women requires an effective partnership with the Department of Corrections, adaptations to traditional community-based participatory research (CBPR) approaches, and resources that support both direct service and ongoing evaluation. CONCLUSIONS: Effective services for pregnant incarcerated women can be provided through a successful community- university-corrections partnership. PMID- 26548789 TI - Using Knowledge Exchange to Build and Sustain Community Support to Reduce Cancer Screening Inequities. AB - BACKGROUND: "Knowledge exchange" (KE) refers to the interaction between knowledge users and researchers toward a goal of mutual learning and collaborative problem solving. METHODS: Using a case study approach, this article describes how researchers leading a multiphase community engagement project, the Peel Cancer Screening Study (PCSS), used KE to engage a community advisory group (CAG) of knowledge users to build community support for interventions to reduce cancer screening inequities for South Asians in Peel Region, Ontario, Canada. RESULTS: As a result of KE activities (concept mapping, a CAG launch meeting, regular CAG meetings, workgroup meetings, a community report), there is currently a resident targeted, community-level program being implemented and a provider-targeted intervention that is funded, with both ethnospecific and health service organizations involved. The process of KE received positive evaluations from advisory group members. CONCLUSIONS: The experiences of the PCSS illustrate the benefits of KE for researchers and community members. PMID- 26548790 TI - CBPR-Informed Recruitment and Retention Adaptations in a Randomized Study of Pap Testing Among Pacific Islanders in Southern California. AB - BACKGROUND: Pacific Islanders (PIs) experience high cervical cancer rates in the United States. Stage of diagnosis is also later for PIs than non-Hispanic Whites. The Pap test is severely underutilized among PIs: only 71% of Asian American and Pacific Islander women age 25 years or older received a Pap test within the last 3 years (U.S. average, 82%). Community-based participatory research (CBPR) is increasingly seen as an essential approach in designing and conducting culturally relevant and appropriate studies that reduce cancer incidence and other health disparities among minority and other medically underserved populations. PURPOSE: The purpose of this article is to describe the lessons learned thus far regarding the identification, recruitment, and retention of PI community organizations and members into a CBPR-informed, randomized, community trial promoting Pap testing. METHODS: This 5-year study used CBPR to develop and test the efficacy of a social support intervention for Chamorro, Samoan, and Tongan women to increase Pap testing in southern California. Eligible women were between the ages of 21 and 65, and married or in a long-term relationship with a man for at least 5 years. Women and their husbands or significant others received a 2-hour, culturally tailored workshop that include a group activity, information on Pap testing, a video, and corresponding materials. Comparison participants received a brochure about Pap testing. Three waves of data are collected from all participants: pretest (before workshop or brochure), posttest 1 (immediately after workshop or brochure), and posttest 2 (6 months follow-up). RESULTS: Of the 76 organizations approached to participate in the study, 67 (88.2%) eventually agreed to participate. Thus far, 473 women and 419 men completed the study pretest, post test, education, and 6-month follow-up. Only 242 women and 204 men of the eligible participants have completed the follow-up survey (63.5% of women and 60.5% of men retained after 6 months). LESSONS LEARNED: The main strategy to overcome initial recruitment challenges was study staff persistence, because they averaged five contacts with each church or clan leader before receiving confirmation that an educational session can be scheduled. Personal connections provided an introduction to the most appropriate church or clan leader. Other efforts for retention include creation of an online version of the survey, re attending church services, and creating special events organized around clan activities. CONCLUSIONS: Although CBPR improves the cultural competence and relevance of study activities for ethnically diverse populations, selected past research shows that it does not ensure that such designs overcome all of the unique challenges in ethnically diverse communities. PI-specific organizational recruitment and individual retention is influenced by study issues and cultural factors in each community. PMID- 26548791 TI - Developing an Academic-Community Partnership to Promote Soccer-Based Physical Activity Among Latino Youth. AB - BACKGROUND: The Latino Health for All (LHFA) Coalition used a community-based participatory approach to develop an action plan for addressing chronic disease among Latinos in Kansas City. OBJECTIVES: This study examines the development and implementation of community-based soccer sessions for youth (ages 6-15) by an academic partner from the coalition and a community partner from a nonprofit youth soccer organization. METHODS: The academic and community partners spoke four times over 3 months to plan for these soccer sessions. These conversations ranged from sharing goals to planning logistics. The coalition helped to promote these opportunities through a variety of channels. RESULTS: Eight weekly soccer sessions were implemented, attracting Latino youth who were overweight or obese. These soccer sessions were perceived as enjoyable by youth and were appreciated by their parents. CONCLUSIONS: Successful health promotion efforts require strong relationships between academic and community partners that involve shared goals and complementary skills/ expertise. PMID- 26548792 TI - The Development of the Milwaukee Consortium for Hmong Health: Capacity Building Through Direct Community Engagement. AB - BACKGROUND: Hmong women experience increased incidence and mortality rates for cervical cancer, yet their cancer risk is often masked by their inclusion within the comparatively low-risk Asian American and Pacific Islander (AAPI) category. Key to this disparity is late stage at diagnosis, a consequence of low rates of screening. OBJECTIVES: This article describes the establishment and community engagement efforts of the Milwaukee Consortium for Hmong Health, established in 2008 to build capacity to investigate and address barriers to screening and cancer care. METHODS: The Consortium facilitated a series of three community dialogues to explore with community members effective ways to overcome barriers to accessing screening and cancer care. RESULTS: The community dialogues produced a series of six recommendations for action, detailed herein, supported and prioritized by the community. CONCLUSIONS: We posit that the integral involvement of the Hmong community from the outset promoted buy-in of ensuing Consortium education and outreach efforts, and helped to ensure fit with community perspectives, needs, and priorities. PMID- 26548793 TI - Data Collection and Management in Community Engaged Research: Lessons Learned From Two Community-Based Participatory Research Partnerships. AB - BACKGROUND: Data collection and data management (DCDM) within community-engaged research (CEnR) requires special considerations that differ from those of traditional research. To date, little guidance exists to preemptively help community-academic partnerships anticipate and resolve DCDM issues that may arise. OBJECTIVE: We sought to provide recommendations for DCDM based on two CEnR research projects. METHODS: We used a case study design to describe the DCDM process and lessons learned that were generated through formal and informal discussions between community and academic partners. LESSONS LEARNED: We identified 4 key lessons: 1) CEnR requires a flexible, iterative approach to DCDM, 2) there are trade-offs to having a flexible DCDM approach, 3) responsibilities for DCDM should consider the skill sets and priorities of all partners, and 4) nuances of DC within CEnR has important implications for human subjects and ethics training. CONCLUSIONS: Based on our lessons learned, we provide recommendations for how to approach DCDM within CEnR. PMID- 26548795 TI - The Exclusionary Circle Game: A Tool to Promote Critical Dialogue About HIV Stigma and Social Justice. AB - BACKGROUND: The Exclusionary Circle Game was a learning tool developed for an intervention study to address stigma associated with human immunodeficiency virus (HIV) infection and social exclusion. OBJECTIVES: The objectives of The Exclusionary Circle Game were to enhance collective resonance and empathy, promote critical reflection and dialogue, and motivate collective action to address social exclusion. METHODS: The game began with all participants being inside a circle. Each participant was randomly given one color-coded card. Each card color represented a character with a specific lived experience associated with racism, patriarchy, homophobia, transphobia, HIV stigma, and so on. Participants holding a marginalized status card were asked to leave the circle in sequence and go to designated spaces. Eventually, only one half of the participants were left in the circle. Participants then debriefed about their experiences within the entire group. CONCLUSIONS: The game has been used, beyond the intervention study, at research conferences with positive feedback. In this article, we detail the processes, strengths, and possibility of using this game for empowerment education. PMID- 26548794 TI - Development of a Faith-Based Stress Management Intervention in a Rural African American Community. AB - BACKGROUND: Faith-based mental health interventions developed and implemented using a community-based participatory research (CBPR) approach hold promise for reaching rural African Americans and addressing health disparities. OBJECTIVES: To describe the development, challenges, and lessons learned from the Trinity Life Management, a faith-based stress management intervention in a rural African American faith community. METHODS: The researchers used a CBPR approach by partnering with the African American faith community to develop a stress management intervention. Development strategies include working with key informants, focus groups, and a community advisory board (CAB). RESULTS: The community identified the key concepts that should be included in a stress management intervention. CONCLUSIONS: The faith-based "Trinity Life Management" stress management intervention was developed collaboratively by a CAB and an academic research team. The intervention includes stress management techniques that incorporate Biblical principles and information about the stress-distress depression continuum. PMID- 26548796 TI - Environmental Justice Radar: A Tool for Community-Based Mapping to Increase Environmental Awareness and Participatory Decision Making. AB - BACKGROUND: As part of the Charleston Area Pollution Prevention Partnership (CAPs), studies have been performed to address environmental health issues using various techniques including Geographic Information Systems (GIS) mapping. Most of the mapping has been conducted by academic team members; however, there is a need for more community-based mapping to ensure the sustainability and effectiveness of community-driven efforts to eliminate environmental hazards and health disparities. The emergence of public participatory GIS (PPGIS) has been shown as a way to democratize science, build community capacity, and empower local citizens to address environmental health issues. PURPOSE: This article describes the development of the Environmental Justice (EJ) Radar, a PPGIS tool that provides stakeholders in South Carolina with a way to raise environmental awareness and improve citizen participation in local environmental decision making. We describe the functionality of EJ Radar and discuss feedback received from stakeholders to improve the utility of the PPGIS tool. PMID- 26548797 TI - Generating National Dental PBRN Research Ideas Through the ToP Consensus Method Workshop. AB - PURPOSE: The purpose of this article is to illustrate the research idea generation process employed by the Southwest Region of the National Dental Practice-Based Research Network (PBRN; www.NationalDentalPBRN.org) based on the Technology of Participation (ToP) Consensus Method Workshop. This method encourages a high level of participation in the decision-making process through individual, small group, and large group discussions. This approach to idea generation has predominately been used by nonprofit organizations and community groups both nationally and internationally, but offers great potential to study concept development for PBRNs. METHOD: Five independent workshops were designed over a 12-month period. Workshops were held at three academic institutions, one National Dental PBRN meeting, and one as part of a continuing education program. The sessions were directed at general dentists, dental hygienists, and dental researchers to identify research ideas appropriate for examination through the PBRN mechanism. RESULT: Five groups ranging in size from 11 to 53 (197 participants total) participated in the consensus workshops and generated 205 research ideas. Ideas across the five sessions were collated into novel and common categories of interest, and identified key participants interested in developing research concepts. Participant reaction to the sessions was positive based on evaluation comments and personal interactions. IMPLICATIONS: Practitioners effectively generated research ideas based on their current needs and daily clinical experience. The experiences presented in this article suggest continued use of the ToP consensus workshop methods within the PBRNs may help bridge the gap between research and practice. PMID- 26548798 TI - Enhancing Community-Based Participatory Research Partnerships Through Appreciative Inquiry. AB - BACKGROUND: Challenges in community-based participatory research (CBPR) partnerships often pertain to trust and power, dilemmas posed by funding sources, and equitable community participation. Although challenges in CBPR can be welcomed because they present opportunities for growth and development of partnerships, tools are needed to facilitate issue identification and resolution. Moreover, such tools need to align with CBPR principles involving equal feedback among partners to improve the partnership and its outcomes. OBJECTIVE: To describe how appreciative inquiry (AI) was used as an evaluation tool to contribute to the strengthening of empowerment of ongoing and future community university relationships in CBPR collaborations. METHODS: AI was applied at the end of a community-university partnership to promote breast and cervical cancer screening among Tongan women in Southern California. Through individual interviews and group discussion, tensions were identified and discussed in light of partnership and community strengths. RESULTS: Through AI, program staff emphasized community and university strengths of shared key values related to the program and aspects of program management that enabled them to contribute to successful program outcomes. They also discussed the following challenges: 1) approach of partners, 2) role definition, and 3) and time span of program development and implementation. Based on these discussions, recommendations were made to overcome current challenges and improve ongoing and future CBPR collaborations. CONCLUSIONS: The AI process helped the partners recommit to collaborate with each other, renewed their excitement about working together, and assisted with reclarification of their roles to inform future collaborations. PMID- 26548799 TI - Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease. AB - Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition. PMID- 26548800 TI - A systematic review of the influence of skin pigmentation on changes in the concentrations of vitamin D and 25-hydroxyvitamin D in plasma/serum following experimental UV irradiation. AB - Defining whether skin pigmentation influences vitamin D photosynthesis is important for delivering accurate public health messages. Current evidence is contradictory. We undertook a systematic review of the published literature to examine the association between skin pigmentation and change in blood concentrations of vitamin D and 25-hydroxyvitamin D following experimental UV irradiation. Twelve studies fulfilled the inclusion criteria: human study in vivo with non-diseased participants; controlled artificial UV radiation; vitamin D or 25-hydroxyvitamin D measured in serum or plasma; full text in English. In seven studies, vitamin D photosynthesis was reduced in dark-skinned compared with fairer-skinned individuals. In the remaining five studies, only one of which was published after 1990, there was no difference in vitamin D photosynthesis according to skin type. The disparities in these results may be due to small sample sizes and variations in study methodology, including the source, dose and frequency of UV irradiation, phototype classification, and analysis of vitamin D and 25-hydroxyvitamin D. Of these, the spectrum emitted by the UV lamps may be significant. No study considered potential modifying factors, such as relevant genetic polymorphisms. On balance, we conclude that pigmented skin has less effective photoproduction of vitamin D and 25-hydroxyvitamin D. The quantity of sun exposure needed for dark-skinned, compared with light-skinned, people to achieve vitamin D sufficiency remains uncertain. PMID- 26548801 TI - Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions. AB - The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils. PMID- 26548802 TI - Epidemiology of Traumatic Injuries in the Northeast Region of Haiti: A Cross sectional Study. AB - INTRODUCTION: More than 90% of traumatic morbidity and mortality occurs in low- and middle-income countries (LMIC). Haiti is the poorest country in the Western Hemisphere and lacks contemporary statistics on the epidemiology of traumatic injuries. This study aimed to characterize the burden of traumatic injuries among emergency department patients in the Northeast region of Haiti. METHODS: Data were collected from the emergency departments of all public hospitals in the Northeast region of Haiti, which included the Fort Liberte, Ouanaminthe, and Trou du Nord sites. All patients presenting for emergent care of traumatic injuries were included. Data were obtained via review of emergency department registries and patient records from October 1, 2013 through November 30, 2013. Data on demographics, mechanisms of trauma, and anatomical regions of injury were gathered using a standardized tool and analyzed using descriptive statistics. Temporal analysis of injury frequency was explored using regression modeling. RESULTS: Data from 383 patient encounters were accrued. Ouanaminthe Hospital treated the majority of emergent injuries (59.3%), followed by Fort Liberte (30.3%) and Trou du Nord (10.4%). The median age in years was 23 with 23.1% of patients being less than 15 years of age. Road traffic accidents (RTAs) and interpersonal violence accounted for 65.8% and 30.1% of all traumatic mechanisms, respectively. Extremity trauma was the most frequently observed anatomical region of injury (38.9%), followed by head and neck (30.3%) and facial (19.1%) injuries. Trauma due to RTA resulted in a single injury (83.8%) to either an extremity or the head and neck regions most frequently. A minority of patients had medical record documentation (37.9%). Blood pressure, respiratory rate, and mental status were documented in 19.3%, 4.1%, and 0.0% of records, respectively. There were 6.3 injuries/day during the data collection period with no correlation between the frequency of emergent trauma cases and day of the week (R(^2)=0.01). CONCLUSIONS: Traumatic injuries are a common emergent presentation in the Northeast region of Haiti with characteristics similar to other LMIC. Documentation and associated data to adequately characterize the burden of disease in this region are lacking. Road traffic accidents are the predominate mechanism of injury, suggesting that interventions addressing prevention and treatment of this common occurrence may provide public health benefits in this setting. PMID- 26548803 TI - Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. AB - Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed. PMID- 26548804 TI - Analysing the effect of crystal size and structure in highly efficient CH3NH3PbI3 perovskite solar cells by spatially resolved photo- and electroluminescence imaging. AB - CH3NH3PbI3 perovskite solar cells with a mesoporous TiO2 layer and spiro-MeOTAD as a hole transport layer (HTL) with three different CH3NH3I concentrations (0.032 M, 0.044 M and 0.063 M) were investigated. Strong variations in crystal size and morphology resulting in diversified cell efficiencies (9.2%, 16.9% and 12.3%, respectively) were observed. The physical origin of this behaviour was analysed by detailed characterization combining current-voltage curves with photo and electroluminescence (PL and EL) imaging as well as light beam induced current measurements (LBIC). It was found that the most efficient cell shows the highest luminescence and the least efficient cell is most strongly limited by non radiative recombination. Crystal size, morphology and distribution in the capping layer and in the porous scaffold strongly affect the non-radiative recombination. Moreover, the very non-uniform crystal structure with multiple facets, as evidenced by SEM images of the 0.032 M device, suggests the creation of a large number of grain boundaries and crystal dislocations. These defects give rise to increased trap-assisted non-radiative recombination as is confirmed by high resolution MU-PL images. The different imaging techniques used in this study prove to be well-suited to spatially investigate and thus correlate the crystal morphology of the perovskite layer with the electrical and radiative properties of the solar cells and thus with their performance. PMID- 26548805 TI - Addition of phenylacetylene to a magnesium complex of monoiminoacenaphtheneone (dpp-mian). AB - In the presence of formic acid, acenaphthenequinone (AQ) reacts with one molar equivalent of 2,6-diisopropylaniline in toluene to give monoiminoacenaphtheneone (3, dpp-mian) in good yield. Reduction of compound 3 with an excess of magnesium in thf results in green crystalline amido-alcoholate [(dpp-mian)Mg(thf)2]2 (4). Crystallization of complex 4 from toluene affords a blue tetramer [(dpp mian)Mg(thf)]4 (5). Reactions of compounds 4 and 5 with phenylacetylene proceed with C-C bond formation between the alkyne and the dpp-mian ligand to give the monomeric alkynyl-magnesium derivative [(dpp-mian)(PhC=CH2)Mg(C=CPh)2(thf)]2 (7). Hydrolysis of complex 5 gives metal-free dpp-mian(PhC=CH2)H (8). Reaction of 7 with acetylacetone yields [{dpp-mian(PhC=CH2)}Mg(acac)]2 (9). Compounds 3-5 and 7 9 have been characterized by IR and NMR spectroscopy; molecular structures of 3, 5, 7, 8 and 9 have been determined by single crystal X-ray analysis. PMID- 26548807 TI - Memory and Combinatorial Logic Based on DNA Inversions: Dynamics and Evolutionary Stability. AB - Genetic memory can be implemented using enzymes that catalyze DNA inversions, where each orientation corresponds to a "bit". Here, we use two DNA invertases (FimE and HbiF) that reorient DNA irreversibly between two states with opposite directionality. First, we construct memory that is set by FimE and reset by HbiF. Next, we build a NOT gate where the input promoter drives FimE and in the absence of signal the reverse state is maintained by the constitutive expression of HbiF. The gate requires ~3 h to turn on and off. The evolutionary stabilities of these circuits are measured by passaging cells while cycling function. The memory switch is stable over 400 h (17 days, 14 state changes); however, the gate breaks after 54 h (>2 days) due to continuous invertase expression. Genome sequencing reveals that the circuit remains intact, but the host strain evolves to reduce invertase expression. This work highlights the need to evaluate the evolutionary robustness and failure modes of circuit designs, especially as more complex multigate circuits are implemented. PMID- 26548806 TI - Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection. AB - The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness. PMID- 26548808 TI - Rates of Reoperation and Abnormal Binocularity Following Strabismus Surgery in Children. AB - PURPOSE: To determine predictors of reoperation and abnormal binocularity outcomes (including amblyopia and diplopia) following pediatric strabismus surgery. DESIGN: Retrospective cross-sectional study. METHODS: setting: Review of a national insurance database. STUDY POPULATION: Children under age 18 years having strabismus procedures between 2007 and 2013. INTERVENTIONS: Adjustable- or fixed-suture strabismus surgery, or botulinum toxin injection. OUTCOME MEASURES: Reoperation or diagnosis of abnormal binocularity in the first postoperative year. RESULTS: Of 11 115 children having strabismus procedures, 851 (7.7%) underwent reoperation. The reoperation rate was 7.4% for fixed-suture surgeries, 9.6% for adjustable-suture surgeries (P = .18), and 44.9% for botulinum injections (P < .001). Age under 2 years was associated with higher reoperation and abnormal binocularity rates (P < .001). For horizontal strabismus, the postoperative abnormal binocularity rate was 12.8% for fixed-suture surgery and 26.5% for botulinum injection (P = .005). Reoperation rates tended to be higher with adjustable sutures (odds ratio [OR] 1.69, 95% confidence interval [CI] 0.94 3.03, P = .08) or botulinum toxin injection (OR 10.36, 95% CI 5.75-18.66, P < .001) and lower with 3- or 4-muscle surgery (P = .001). Esotropia, hyperopia, and botulinum injection were independently associated with higher rates of postoperative abnormal binocularity (P <= .005). For vertical surgeries, predictors of reoperation were adjustable-suture use (OR 2.51, P = .10) and superior oblique surgery (OR 2.36, P < .001). CONCLUSIONS: Adjustable sutures were not associated with a lower reoperation rate in children. Younger age, esotropia, hyperopia, and botulinum injection were associated with postoperative abnormal binocularity. Superior oblique surgery and botulinum injection were associated with higher rates of reoperation. PMID- 26548809 TI - Three-Dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography. AB - PURPOSE: To analyze the vitreoretinal interface in diabetic eyes using 3 dimensional wide-field volumes acquired using high-speed, long-wavelength swept source optical coherence tomography (SSOCT). DESIGN: Prospective cross-sectional study. METHODS: Fifty-six diabetic patients (88 eyes) and 11 healthy nondiabetic controls (22 eyes) were recruited. Up to 8 SSOCT volumes were acquired for each eye. A registration algorithm removed motion artifacts and merged multiple SSOCT volumes to improve signal. Vitreous visualization was enhanced using vitreous windowing method. RESULTS: Of 88 diabetic eyes, 20 eyes had no retinopathy, 21 eyes had nonproliferative diabetic retinopathy (NPDR) without macular edema, 20 eyes had proliferative diabetic retinopathy (PDR) without macular edema, and 27 eyes had diabetic macular edema (DME) with either NPDR or PDR. Thick posterior hyaloid relative to healthy nondiabetic controls was observed in 0 of 20 (0%) diabetic eyes without retinopathy, 4 of 21 (19%) eyes with NPDR, 11 of 20 (55%) eyes with PDR, and 11 of 27 (41%) eyes with DME (P = .0001). Vitreoschisis was observed in 6 of 22 (27%) healthy nondiabetic eyes, 9 of 20 (45%) diabetic eyes without retinopathy, 10 of 21 (48%) eyes with NPDR, 13 of 20 (65%) eyes with PDR, and 17 of 27 (63%) eyes with DME (P = .007). While no healthy nondiabetic controls and diabetic eyes without retinopathy had adhesions/pegs between detached posterior hyaloid and retina, 1 of 21 (4%), 11 of 20 (55%), and 11 of 27 (41%) eyes with NPDR, PDR, and DME, respectively, demonstrated this feature (P = .0001). CONCLUSION: SSOCT with motion-correction and vitreous windowing provides wide-field 3-dimensional information of vitreoretinal interface in diabetic eyes. This may be useful in assessing progression of retinopathy, planning diabetic vitreous surgery, and predicting treatment outcomes. PMID- 26548810 TI - Efficacy of a Single Dose of Basic Fibroblast Growth Factor: Clinical Observation for 1 Year. AB - OBJECTIVE: Basic fibroblast growth factor promotes wound healing by accelerating healthy granulation and epithelialization. However, the duration of the effects of a single intracordal injection of basic fibroblast growth factor has not been established, and administration intervals and timing have yet to be standardized. Here, we administered a single injection to patients with insufficient glottic closure and conducted follow-up examinations with high-speed digital imaging to determine the duration of the treatment response. STUDY DESIGN: Case series. METHODS: For treatment, 20 ug/mL recombinant human basic fibroblast growth factor was injected into two vocal cords. The following examinations were performed before the procedure and at 3-month intervals for 12 months starting at 1 month postinjection: Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale assessment, maximum phonation time, acoustic analysis, high-speed digital imaging, glottal wave analysis, and kymographic analysis. RESULTS: Postinjection, the GRBAS scale score decreased, and the maximum phonation time was prolonged. In addition, the mean minimum glottal area and mean minimum glottal distance decreased. These changes were significant at 12 months postinjection compared with preinjection. However, there were no significant changes in the vibrations of the vocal cord margins. CONCLUSIONS: The intracordal injection of basic fibroblast growth factor improved insufficient glottic closure without reducing the vibrations of the vocal cord margins. This effect remained evident at 12 months postinjection. A single injection can be expected to yield a sufficient and persistent long-term effect. PMID- 26548811 TI - On binocular vision: The geometric horopter and Cyclopean eye. AB - We study geometric properties of horopters defined by the criterion of equality of angle. Our primary goal is to derive the precise geometry for anatomically correct horopters. When eyes fixate on points along a curve in the horizontal visual plane for which the vergence remains constant, this curve is the larger arc of a circle connecting the eyes' rotation centers. This isovergence circle is known as the Vieth-Muller circle. We show that, along the isovergence circular arc, there is an infinite family of horizontal horopters formed by circular arcs connecting the nodal points. These horopters intersect at the point of symmetric convergence. We prove that the family of 3D geometric horopters consists of two perpendicular components. The first component consists of the horizontal horopters parametrized by vergence, the point of the isovergence circle, and the choice of the nodal point location. The second component is formed by straight lines parametrized by vergence. Each of these straight lines is perpendicular to the visual plane and passes through the point of symmetric convergence. Finally, we evaluate the difference between the geometric horopter and the Vieth-Muller circle for typical near fixation distances and discuss its possible significance for depth discrimination and other related functions of vision that make use of disparity processing. PMID- 26548812 TI - The repellent and persistent toxic effects of essential oils against the poultry red mite, Dermanyssus gallinae. AB - The economic impact of the poultry red mite, Dermanyssus gallinae, the lack of new acaricides, the occurrence of resistance and tighter legislation have all led to the need to find new ways to control this pest. One promising alternative method of control focuses on employing repellent and/or toxic effects of selected plant essential oils against D. gallinae. Ten essential oils (basil, thyme, coriander, eucalyptus, lavender, lemon, fir tree, oregano, mint, and juniper) were tested for the persistence of toxic and repellent effects. In filter-paper toxicity bioassays against D. gallinae, the best results were observed for lavender (more than 97% mortality after 48 and 72 h) and thyme (84% at 72 h) at a dose of 0.12 mg/cm(2). In addition, two oils showed significant persistent toxic effects 15 and 30 days post application to filter papers. Thyme was the most effective (100% mortality at 72 h), followed by lavender (nearly 80% mortality after 72 h). Out of the ten oils tested for their repellent effect, thyme was the strongest, with nearly 80% of the tested area avoided by mites; oregano caused a 60% avoidance and lavender exhibited an effect close to 40%. All other oils exhibited a repellent effect of less than 30%. None of the experiments showed a repellent effect for HM (commercial alimentary oil) or negative controls. We found that the thyme and lavender essential oils exhibited promising results when tested in vitro for toxic and repellent effects against D. gallinae; thus, we suggest that future experiments focus on in vivo tests using these oils in farm units. PMID- 26548813 TI - Serum and glucocorticoid kinase 1 promoted the growth and migration of non-small cell lung cancer cells. AB - Serum and glucocorticoid kinase 1 (SGK1) has been reported to be up-regulated in non-small cell lung cancer (NSCLC). However, its functions in NSCLC remained unclear. Here, SGK1 was found to be up-regulated in NSCLC samples. Over expression of SGK1 promoted the growth and migration of NSCLC cells, while down regulation of SGK1 inhibited the growth, migration and metastasis of NSCLC cells. SGK1 promoted the phosphorylation of GSK3 beta and the accumulation of beta catenin, up-regulation of the target genes downstream of beta-catenin/TCF signaling, and activating the transcriptional activity of beta-catenin/TCF complex. Collectively, SGK1 might promote the progression of NSCLC through activating beta-catenin/TCF signaling. PMID- 26548815 TI - Molecular cloning, expression analysis and subcellular localization of a Transparent Testa 12 ortholog in brown cotton (Gossypium hirsutum L.). AB - Transparent Testa 12 (TT12) is a kind of transmembrane transporter of proanthocyanidins (PAs), which belongs to a membrane-localized multidrug and toxin efflux (MATE) family, but the molecular basis of PAs transport is still poorly understood. Here, we cloned a full-length TT12 cDNA from the fiber of brown cotton (Gossypium hirsutum), named GhTT12 (GenBank accession No. KF240564), which comprised 1733 bp with an open reading frame (ORF) of 1503 bp and encoded a putative protein containing 500 amino acid residues with a typical MATE conserved domain. The GhTT12 gene had 96.8% similarity to AA genome in Gossypium arboretum. Quantitative RT-PCR analysis denoted that the relative expression of GhTT12 in brown cotton was 1-5 folds higher than that in white cotton. The mRNA level was the highest at 5 days post anthesis (DPA) and reduced gradually during the fiber development. Expressing GhTT12-fused green fluorescent protein (GFP) in Nicotiana tabacum showed that GhTT12-GFP was localized in the vacuole membrane. The content of PAs increased firstly and decreased afterwards, and reached the maximum at 15 DPA in brown cotton. But for white cotton, the content of PAs remained at a low level during the fiber development. We speculate that GhTT12 may participate in the transportation of PAs from the cytoplasmic matrix to the vacuole. Taken together, our data revealed that GhTT12 was functional as a PAs transmembrane transporter. PMID- 26548814 TI - Jagged1 (JAG1): Structure, expression, and disease associations. AB - Jagged1 (JAG1) is one of the 5 cell surface ligands that functions primarily in the highly conserved Notch signaling pathway. Notch signaling plays a critical role in cellular fate determination and is active throughout development and across many organ systems. The classic JAG1-NOTCH interaction leads to a cascade of proteolytic cleavages resulting in the NOTCH intracellular domain being transported into the nucleus where it functions to activate downstream transcription of target genes. JAG1 mutations have been associated with several disorders including the multi-system dominant disorder Alagille syndrome, and some cases of tetralogy of Fallot (although these may represent variable expressivity of Alagille syndrome). In addition, variations in JAG1 have been found to be associated with multiple types of cancer including breast cancer and adrenocortical carcinoma. Alagille syndrome, which primarily affects the liver, heart, skeleton, eye, face, kidney and vasculature is caused by loss of function mutations in JAG1, demonstrating that haploinsufficiency for JAG1 is disease causing, at least in these tissues. Expression and conditional gene knockout studies of JAG1 (Jag1) have correlated with tissue-specific disease phenotypes and have provided insight into both disease pathogenesis and human development. PMID- 26548816 TI - Angioarchitecture and Posttreatment Magnetic Resonance Imaging Characteristics of Brain Arteriovenous Malformations and Long-Term Seizure Control After Radiosurgery. AB - OBJECTIVE: To corroborate which pretreatment angioarchitectural characteristics and posttreatment magnetic resonance imaging (MRI) features were associated with better seizure and antiepileptic drug outcomes in patients with brain arteriovenous malformations (AVMs) treated by Gamma Knife radiosurgery. METHODS: During the period 2007-2010, 220 patients with intracranial AVMs undergoing radiosurgery at our hospital were evaluated. Imaging features on digital subtraction angiography and follow-up MRI, medical records, and direct patient interview were retrospectively assessed. Seizure outcome was assessed using the Engel classification and the status of antiepileptic drug use. RESULTS: At the last follow-up, 21 of 31 patients (68%) who met the recruitment criteria had AVM obliteration on digital subtraction angiography or MRI. Seizure-free status (Engel class 1) was achieved in 20 patients (65%), and 13 of 20 (65%) seizure free patients were medication-free. The presence of total obliteration at last imaging follow-up (P = 0.013), absent retrograde cortical veins on digital subtraction angiography before GKRS (P = 0.013), nidus <3.7 cm (P = 0.006), and lower modified radiosurgery-based AVM score (P = 0.026) were significant predictors of seizure-free outcome. The strongest independent predictor of seizure-free status was absence of retrograde veins (odds ratio = 9.9). No angioarchitectural feature, postradiosurgery imaging finding on MRI, or radiosurgical treatment parameter was a significant predictor of seizure control or cessation of medication in seizure-free patients. CONCLUSIONS: This study suggests that radiosurgery provides favorable outcomes in patients with AVM related epilepsy. Patients with intracranial AVMs can benefit from seizure control after GKRS before undergoing AVM obliteration. Absence of retrograde veins is associated with better seizure-free outcomes, regardless of the parenchymal changes after radiosurgery. PMID- 26548817 TI - Predictive Factors for Response of Intracranial Dural Arteriovenous Fistulas to Transarterial Onyx Embolization: Angiographic Subgroup Analysis of Treatment Outcomes. AB - OBJECTIVE: Endovascular treatment using Onyx has been increasingly used to treat intracranial dural arteriovenous fistulas (DAVFs). This study evaluated predictive factors for favorable treatment outcome in patients with intracranial noncavernous DAVFs treated by transarterial Onyx embolization. METHODS: Between August 2008 and August 2014, 55 patients who underwent transarterial Onyx embolization for noncavernous DAVFs were retrospectively reviewed. Patients' demographic, clinical, and procedural data were analyzed to find statistically significant predictive factors for favorable treatment outcomes after Onyx embolization. Fistulas were classified angiographically according to the relationship between fistulas and dural venous sinuses and the presence of leptomeningeal venous reflux. RESULTS: Sixty-eight Onyx embolizations were performed in 55 patients. Immediate angiographic cure was achieved in 28 patients, and 14 of 27 patients with residual shunts showed progressive occlusion at follow-up imaging studies. Therefore, the overall favorable treatment outcome was 76.4% (42/55). The remaining 13 patients (23.6%) showed persistent residual shunts, and 3 (5.5%) of them showed aggravation of residual lesion on follow-up studies. Of 25 patients with non-sinus fistulas, 23 patients (92%) showed favorable treatment outcomes, and 19 of 30 patients (63.3%) with sinus fistulas showed favorable outcomes. Among the evaluated variables, non-sinus DAVFs was a statistically significant predictive factor for favorable response to transarterial Onyx embolization (P < 0.05). CONCLUSIONS: Transarterial Onyx embolization is a highly effective treatment method for non-sinus DAVFs. Careful consideration of angiographic features and multimodal embolization strategies are required for treatment of sinus DAVFs. PMID- 26548818 TI - Mortality in Elderly Patients Operated for an Acute Subdural Hematoma: A Surgical Case Series. AB - BACKGROUND: Surgery for elderly patients with acute subdural hematomas (ASDH) is controversial, because postoperative mortality rates are reported to be high and long-term outcomes unknown. Thus, we aimed to describe midterm and long-term mortality rates of elderly patients operated for an ASDH. METHODS: We reviewed all consecutive >=75-year-old patients operated on for an ASDH between 2009 and 2012. We recorded data on preadmission functional status (independent or dependent) and use of antithrombotic medication. Patients were followed up a median of 4.2 years (range, 2.5-6.4 years). RESULTS: Forty-four patients were included. The majority of the patients (70%) were independent and taking antithrombotic medication (77%). Independent patients had a 1-year mortality of 42%, compared to 69% for dependent patients; 56% of patients taking antithrombotics and 30% of those without antithrombotics died within the first postoperative year. All patients with an admission Glasgow coma scale score of 3 8 died within the first postoperative year, if they used antithrombotics or were dependent before the injury. Of all 1-year survivors, 77% were alive at the end of follow-up. CONCLUSION: In this first surgical case series of 75-year-old or older patients with ASDH, the overall mortality rate appears to be relatively low, especially for preoperatively conscious and independent patients without antithrombotic medication. Patients alive at 1-year after surgery had a life expectancy comparable to their age-matched peers. The prognosis seems to be detrimental for preoperatively unconscious patients who were functionally dependent or used antithrombotic medication before the injury. PMID- 26548819 TI - Cavernous Malformation in the Trigeminal Distribution: A Case Report of Aggressive Presentation and Management. AB - BACKGROUND: Cavernous malformation (CM) is a vascular malformation found in the encephalic parenchyma, spinal cord, nerve roots, and extraneural tissue. CM in the trigeminal distribution is exquisitely uncommon and its biological behavior not completely understood. The clinical picture might be diverse, depending on the affected sector of the trigeminal architecture, and literature debating its pathobiology is scarce. CASE DESCRIPTION: We describe a case of 56-year-old woman who presented with left trigeminal neuralgia and a rapidly growing cavernous malformation of the entire distribution of the fifth nerve. The clinical picture evolved to a progressive gait ataxia and follow-up neuroimaging showed a large intracranial mass leading to a brainstem compression. After microsurgical resection, the mass proved to be a typical CM of the trigeminal root. CONCLUSION: We present an uncommonly aggressive progression of a CM of the trigeminal root, Gasserian ganglion, and cavernous sinus evolving to severe brainstem compression. The documentation of this unique case as well as its management is presented is discussed. PMID- 26548820 TI - A Singular Case of Neurosyphilis Manifesting Through a Meningovascular Chronic Inflammatory Process in Association with the Occurrence of Two Aneurysms Involving the Distal A2 Segment of Both Anterior Cerebral Arteries: A Case Report and Review of the Literature. AB - BACKGROUND: Although syphilis has become a rare disease in the Western world since the Second World War, it is believed to have infected 12 million people in 1999, with greater than 90% of cases occurring in the developing world. Moreover, since the year 2000, the rates of syphilis have been increasing in the United States, the United Kingdom, Australia, and Europe. Because of the mimic nature of the disease and the overall low rate of occurrence of its manifestations in advanced stages, a proper diagnosis may prove difficult. CASE REPORT: We report the case of a 41-year-old African man affected by neurosyphilis that manifested itself through a meningovascular chronic inflammatory process, with the peculiar feature of a bilateral aneurysm of probable mycotic origin involving the distal tract of A2 segment of both anterior cerebral arteries. CONCLUSIONS: Because of the mostly nonspecific nature of clinical manifestations of syphilis (particularly advanced syphilis) and its consequent tendency to masquerade as many other diseases, even a skilled physician may find its diagnosis quite challenging; thus, thorough clinical and radiologic investigations should be supported by serologic testing for syphilis in all cases of cognitive impairment. Mycotic intracranial aneurysms in association with neurosyphilis rarely are reported; however, they require early diagnosis and meticulous, individualized treatment. Because syphilis appears to be on the raise, further studies on the topic are warranted. PMID- 26548821 TI - Surviving the Largest Atypical Parasagittal Meningioma in a 2-Year-Old Child: A Case Report and a Brief Review of the Literature. AB - BACKGROUND: Meningiomas arising in pediatric populations are rare neoplasms with distinct biological and clinical features. A rare case of a 2-year-old boy with extremely large intracranial parasagittal meningioma is presented. To our knowledge, this case is the largest parasagittal meningioma to be reported to date in the pediatric age group. CASE DESCRIPTION: The tumor size at its largest diameter was 14.2 cm. Two-stage craniotomy was performed within 3 weeks to resect the tumor totally by Simpson grade II while preserving the superior sagittal sinus. Three months after the second resection, the patient had a complication of subdural hematoma, which was managed by external drainage and urokinase. CONCLUSIONS: The patient's postoperative recovery was unremarkable, and the previously compressed brain rebounded. There was no evidence of recurrence after two years of follow-up. Every effort should be exerted to achieve radical resection of the tumor, which can result in a satisfactory prognosis and a low recurrence rate. PMID- 26548822 TI - The Geriatric Scoring System (GSS) for Risk Stratification in Meningioma Patients as a Predictor of Outcome in Patients Treated with Radiosurgery. AB - INTRODUCTION: Meningiomas are the most common primary benign brain tumor. Radiosurgery (primary or adjuvant) allows excellent local control. The Geriatric Scoring System (GSS) for preoperative risk stratification and outcome prediction of patients with meningiomas has been reported previously. The GSS incorporates 8 tumor and patient parameters on admission. A GSS score greater than 16 was reported previously to be associated with a more favorable outcome. We assessed the validity of the GSS score and its influence on outcome in patients treated with Gamma-Knife radiosurgery (GKRS). PATIENTS AND METHODS: Patients treated with single-session GKRS for World Health Organization grade I meningioma during 1989 2013 at the University of Virginia were reviewed. The cohort comprised 323 patients, 50.2% (n = 162) male. Median age was 56 years (29-84 years), and median follow-up was 53.6 months (6-235 months). Median tumor volume was 4.5 cm(3) (0.2 23). Median margin and maximal doses were 15 Gy (8-36) and 32.3 Gy (20-65), respectively. RESULTS: Tumor volume control was achieved in 87% (n = 281), and post-GKRS clinical neurologic improvement was reported in 66.3% (n = 214). The median change in KPS was +10 (range -30 to +40). The most common complication was intermittent headaches (34.1%, n = 110) and cranial nerve deficits (14.2%, n = 46). The GSS (calculated and grouped as GSS > 16 and GSS <= 16) was found to correlate with different post-GKRS functional status (P < 0.0001) and tumor control (P = 0.028). CONCLUSION: The GSS, used for risk stratification and outcome prediction in patients with meningiomas, seems valid for patients undergoing single-session GRKS. A GSS score greater than 16 is associated with a better long-term functional status and tumor control. PMID- 26548823 TI - Surgical Strategy for Complex Anterior Cerebral Artery Aneurysms: Retrospective Case Series and Literature Review. AB - OBJECTIVE: Giant, or complex, aneurysms of the anterior cerebral artery (ACA) are rare, but their surgical treatment is important. The authors describe their experiences with bypasses for complex ACA aneurysms and discuss the new classification of ACA bypasses, the concept of using bypasses for insurance during the approach to the aneurysm, and simplifying the surgical algorithms for these complex ACA aneurysms. METHODS: Over a 19-year period, 7 cases of complex ACA aneurysm were treated with bypasses and reviewed retrospectively. The bypasses were classified into 4 groups according to donor blood flow: internal carotid artery-ACA, external carotid artery-ACA, communicating bypass, and reconstruction bypass of the ipsilateral postcommunicating ACA. RESULTS: The cases included 1 precommunicating aneurysm, 3 communicating aneurysms, 2 postcommunicating aneurysms, and 1 double aneurysm (communicating and postcommunicating). The types of bypass included 1 internal carotid artery-ACA, 6 communicating bypasses, 3 external carotid artery-ACAs, and 2 reconstruction bypass of the postcommunicating ACA. Postoperative modified Rankin Scale scores were 0 (6 cases) and 3 (1 case of a communicating aneurysm with complicated memory disturbance because of infarction). One case revealed asymptomatic infarction. CONCLUSIONS: Surgical treatment of complex ACA aneurysms requires knowledge of a variety of bypass techniques. Although the type of bypass should be selected according to patient-specific anatomy and the neurosurgeon's preference, the new classification of bypass-specified ACA aneurysms may alter the way surgeons think about ACA bypasses, and in combination with the concept of the protective bypass, can be used to establish a comprehensive algorithm for each type of complex ACA aneurysm. PMID- 26548824 TI - Bony Regeneration of the Sella after Transsphenoidal Pituitary Surgery. AB - OBJECTIVE: The purpose of this study is to demonstrate the possible bony regrowth of the sella after transsphenoidal surgery without any intraoperative sellar reconstruction. METHODS: Radiologic findings of the sella were reviewed in patients with pituitary tumors treated by transsphenoidal surgery. In 17 patients who had postoperative cranial computed tomography scans, bony regeneration of the sellar floor was evaluated by comparing immediate and late postoperative scans. The bony opening reduction was measured in transverse and sagittal planes. RESULTS: The median bony opening diameter in the transverse plane was 8.8 mm (interquartile range [IQR] 5.7-11.4) on the first scan and 4.2 mm (IQR 0.8-6.8) on the second scan. In the sagittal plane, it was 4.8 mm (IQR 1.8-6.8) on the first scan and 2.9 mm (IQR 1.6-3.9) on the second scan. These changes occurred in a median time of 36 months (IQR 22-42). There was a statistically significant decrease of the bony opening diameters in both the transverse and sagittal planes (P < 0.0001 and P = 0.0004, respectively). Bone regeneration was observed in 16 of the 17 patients (approximately 94%). CONCLUSION: There is a natural bony regeneration of the sella after transsphenoidal pituitary surgery. PMID- 26548825 TI - Safe Resection of Gliomas of the Dominant Angular Gyrus Availing of Preoperative FMRI and Intraoperative DTI: Preliminary Series and Surgical Technique. AB - OBJECTIVE: Language dysfunction, visual deficit, numeracy impairment, and Gerstmann syndrome often occur in the cortical area; furthermore, the subcortical white matter is the inviolable limit of "functional neurosurgery." Preoperative functional magnetic resonance imaging (fMRI) and tractography are capable of providing the data required for safe "surgical planning" at both the cortical and subcortical levels. METHODS: We report our experience regarding high-grade gliomas affecting the dominant angular gyrus (AG), supramarginal gyrus (SMG), intraparietal sulcus (IPS), and their respective subcortical areas using intraoperative MRI and diffusion tensor imaging (DTI). Retrospectively, we reviewed a consecutive series of 27 patients operated in a BrainSuite for high grade intraparenchymal tumors of the left posterior temporoparietal junction. We included tumors involving the dominant AG, SMG, and/or IPS and the subcortical course of arcuate fasciculus (AF) and all the patients who underwent preoperative fMRI and DTI to localize the AF and the eloquent cortical areas. Just after craniotomy, new volumetric MRI and DTI verified and corrected possible brain shift. After the gross total resection was carried out, and before approaching the residual mass close to the white matter tract, an intraoperative MRI was again performed. RESULTS: We operated on 27 patients, 15 males and 12 females, whose diagnosis was always high-grade glioma. During the preoperative neurologic examination, 6 patients were asymptomatic; 3 presented a Gerstmann syndrome; 16 showed dysphasic disturbances, 6 of which were associated with visual field deficits; and 2 showed weakness of the right limb. CONCLUSIONS: Our results suggest that this approach is completely safe and effective as an alternative to awake surgery. PMID- 26548826 TI - Penetration of an Optic Nerve by a Sellar/Suprasellar Arachnoid Cyst. AB - BACKGROUND: Sellar/suprasellar cystic lesions can cause compression of the optic pathways and result in a decline in vision. There have been reports of optic pathways being fenestrated by intracranial aneurysms. This is the first report of a sellar/suprasellar arachnoid cyst causing fenestration of an optic nerve. CASE DESCRIPTION: Our patient presented with an 8-month history of worsening vision. Imaging revealed a sellar/suprasellar cystic lesion with compression of the optic pathways. He was treated surgically via an endoscopic transsphenoidal approach. The left optic nerve was found to have multiple round defects during surgery. Pathology was consistent with an arachnoid cyst. The patient has had progressive improvement in vision up to 6 months after surgery. CONCLUSIONS: Sellar/suprasellar arachnoid cysts likely form when a communication exists between the suprasellar arachnoid space and the sella turcica. We believe that our patient's cyst grew slowly enough to allow normal functioning of the optic nerve as it was being penetrated. Though visual symptoms may be gradual and not present until after the optic nerve has been penetrated, these symptoms and signs may still improve with removal of the cyst. Prognosis for visual improvement is difficult to predict with cases of compressive sellar/suprasellar cystic masses. Improvement in the vision examination after surgical resection is possible even when the optic nerve has been penetrated. PMID- 26548827 TI - Intraoperative Evaluation of Reverse Bypass Using a Naturally Formed "Bonnet" Superficial Temporal Artery: Technical Note. AB - BACKGROUND: In reverse bypass that used a naturally formed "bonnet" superficial temporal artery, intraoperative volume flow measurement quantifies flow augmentation after revascularization, confirms flow preservation, and identifies inadvertent vessel compromise. CASE DESCRIPTION: A 75-year-old man presented with transient ischemic attacks attributed to right internal carotid artery stenosis. He underwent successful reverse bypass via a naturally formed "bonnet" superficial temporal artery middle cerebral artery bypass. As the result of proper intraoperative volume flow evaluation, a successful reverse bypass was achieved. CONCLUSIONS: Modification of the intraoperative stroke risk and prediction of the long-term patency after reverse bypass can be achieved by meticulous intraoperative blood flow evaluation. PMID- 26548828 TI - Cost-Effectiveness Analysis of Microscopic and Endoscopic Transsphenoidal Surgery Versus Medical Therapy in the Management of Microprolactinoma in the United States. AB - BACKGROUND: Although prolactinomas are treated effectively with dopamine agonists, some have proposed curative surgical resection for select cases of microprolactinomas to avoid life-long medical therapy. We performed a cost effectiveness analysis comparing transsphenoidal surgery (either microsurgical or endoscopic) and medical therapy (either bromocriptine or cabergoline) with decision analysis modeling. METHODS: A 2-armed decision tree was created with TreeAge Pro Suite 2012 to compare upfront transsphenoidal surgery versus medical therapy. The economic perspective was that of the health care third-party payer. On the basis of a literature review, we assigned plausible distributions for costs and utilities to each potential outcome, taking into account medical and surgical costs and complications. Base-case analysis, sensitivity analysis, and Monte Carlo simulations were performed to determine the cost-effectiveness of each strategy at 5-year and 10-year time horizons. RESULTS: In the base-case scenario, microscopic transsphenoidal surgery was the most cost-effective option at 5 years from the time of diagnosis; however, by the 10-year time horizon, endoscopic transsphenoidal surgery became the most cost-effective option. At both time horizons, medical therapy (both bromocriptine and cabergoline) were found to be more costly and less effective than transsphenoidal surgery (i.e., the medical arm was dominated by the surgical arm in this model). Two-way sensitivity analysis demonstrated that endoscopic resection would be the most cost-effective strategy if the cure rate from endoscopic surgery was greater than 90% and the complication rate was less than 1%. Monte Carlo simulation was performed for endoscopic surgery versus microscopic surgery at both time horizons. This analysis produced an incremental cost-effectiveness ratio of $80,235 per quality adjusted life years at 5 years and $40,737 per quality-adjusted life years at 10 years, implying that with increasing time intervals, endoscopic transsphenoidal surgery is the more cost-effective treatment strategy. CONCLUSIONS: On the basis of the results of our model, transsphenoidal surgical resection of microprolactinomas, either microsurgical or endoscopic, appears to be more cost effective than life-long medical therapy in young patients with life expectancy greater than 10 years. We caution that surgical resection for microprolactinomas be performed only in select cases by experienced pituitary surgeons at high volume centers with high biochemical cure rates and low complication rates. PMID- 26548829 TI - Glioblastoma with Rhabdoid Features: Report of Two Young Adult Cases and Review of the Literature. AB - BACKGROUND: There are few previous reports of glioblastoma in young adults, in particular, of the very rare recently proposed rhabdoid or epithelioid types. CASE DESCRIPTION: We report 2 cases of glioblastoma with rhabdoid features involving a 27-year-old woman and a 41-year-old man. In case 1, the patient presented with generalized seizures, and the initial magnetic resonance imaging showed a very small region of contrast in the left parahippocampal area. After 1 year, the mass suddenly increased in size. Treatment with multiple therapies was administered, but 5 months later, the patient died from multiple systemic metastases. In case 2, the patient presented with a chief complaint of headache for a few weeks. Computed tomography and magnetic resonance imaging showed a left parietal mass with calcification and meningeal dissemination. After undergoing surgical removal, his condition rapidly deteriorated until brain death occurred. CONCLUSIONS: Glioblastoma with rhabdoid features may represent a specific pattern of clinical progression that emerges from histologic glioblastoma types. PMID- 26548830 TI - Management of Bilateral Hemifacial Spasm with Microvascular Decompression. AB - BACKGROUND: Bilateral hemifacial spasm (HFS) is very rare. The literature contains only 32 clinical reports. Although microvascular decompression (MVD) is widely accepted as effective therapy for HFS, the etiology and surgical treatment of bilateral HFS are seldom addressed. We report our experience with MVD for patients with bilateral HFS. METHODS: This retrospective report included 10 patients with bilateral HFS. All patients underwent MVD 1 or 2 times and were followed for 5-92 months. The clinical data were retrospectively analyzed. The etiology and treatment strategies were discussed. RESULTS: Spasm stopped completely on the operative side in all 10 patients. Symptoms on the other side also resolved in 3 patients, improved in 1 patient, and did not improve at all in 6 patients. Of the 6 patients with no improvement, 5 underwent another MVD on the contralateral side within 1 year and experienced relief of symptoms, and 1 patient refused the surgery. The neurovascular conflict was found in all the operations. During the follow-up period, no complications of hearing loss or facial palsy and no recurrence were observed. CONCLUSIONS: Vascular compression was the cause of bilateral HFS in our patients, and MVD relieved the symptoms. Thus, we recommend MVD for patients with bilateral HFS. A crowded cerebellopontine angle space and easy attrition of the neurovascular interfaces may play important roles in the occurrence of bilateral HFS. For some patients, 1 MVD can resolve bilateral symptoms. PMID- 26548831 TI - New Radiologic Parameters Predict Clinical Outcome after Decompressive Craniectomy. AB - OBJECTIVE: Decompressive craniectomy (DC) is an established part of the management of patients with increased intracranial pressure due to malignant middle cerebral artery (MCA) infarction or traumatic brain injury (TBI). The aim of this study was to determine prognostic radiologic parameters regarding the functional outcome of patients with increased intracranial pressure (ICP) undergoing DC. Special focus was put on the potential differences between malignant MCA infarction and TBI. METHODS: A total of 113 patients were analyzed for their clinical course where preoperative and postoperative radiologic features in computed tomography (CT) scans were correlated to the clinical outcome assessed by the Glasgow Outcome Scale. The difference between presurgical and postsurgical midline shift (DeltaMLS) and the ratio between the diameter of the affected and contralateral hemisphere (HDratio) in presurgical and postsurgical CT scans were calculated. RESULTS: DeltaMLS (MCA infarction group) and postsurgical HDratio (TBI group) were found to be highly correlating with the clinical outcome on Spearman-correlation testing and underwent further analysis using a binary logistic regression model to evaluate their prognostic value on the outcome, which showed the predictive power of DeltaMLS in malignant MCA infarction patients (odds ratio [OR] 0.715; confidence interval [CI] 0.551 0.865). Postsurgical HDratio correlated significantly (OR 0.620; CI 0.384-0.901) with the outcome in the TBI group. CONCLUSION: DeltaMLS is an objectifiable parameter, predicting outcome in malignant MCA infarction. In contrast, DeltaMLS was of no predictive value in TBI patients. Here postsurgical HDratio serves as a strong predictor of clinical outcome. We recommend applying postsurgical HDratio to TBI patients in order to estimate their clinical outcome and adjust treatment. PMID- 26548832 TI - Assessing Patient Reported Outcomes Measures via Phone Interviews Versus Patient Self-Survey in the Clinic: Are We Measuring the Same Thing? AB - BACKGROUND: Longitudinally following patients requires a full-time employee (FTE) dependent data inflow infrastructure. There are efforts to capture patient reported outcomes (PROs) by the use of non-FTE-dependent methodologies. In this study, we set out to assess the reliability of PRO data captured via FTE dependent compared with non-FTE-dependent methodologies. METHODS: A total of 119 adult patients (65 men) who underwent 1-and 2-level lumbar fusions at Duke University Medical Center were enrolled in this prospective study. Enrollment criteria included available demographic, clinical, and PRO data. All patients completed 2 sets of questionnaires--the first a phone interviews and the second a self-survey. There was at least a 2-week period between the phone interviews and self-survey. Questionnaires included the Oswestry Disability Index (ODI), the visual analog scale for back pain (VAS-BP), and the visual analog scale for leg pain (VAS-LP). Repeated-measures analysis of variance was used to compare the reliability of baseline PRO data captured. RESULTS: A total of 39.49% of patients were smokers, 21.00% had diabetes, and 11.76% had coronary artery disease; 26.89% reported history of anxiety disorder, and 28.57% reported history of depression. A total of 97.47% of patients had a high-school diploma or General Education Development, and 49.57% attained a 4-year college degree or postgraduate degree. We observed a high correlation between baseline PRO data captured between FTE dependent versus non-FTE dependent methodologies (ODI: r = -0.89, VAS-BP: r = 0.74, VAS-LP: r = 0.70). There was no difference in PROs of baseline pain and functional disability between FTE-dependent and non-FTE-dependent methodologies: baseline ODI (FTE-dependent: 47.73 +/- 16.77 [mean +/- SD] vs. non-FTE-dependent: 45.81 +/- 12.11, P = 0.39), VAS-LP (FTE-dependent: 6.13 +/- 2.78 vs. non-FTE dependent: 6.46 +/- 2.79, P = 0.36) and VAS-BP (FTE-dependent: 6.33 +/- 2.90 vs. non-FTE-dependent: 6.53 +/- 2.48, P = 0.57). CONCLUSION: Our study suggests that there is great reliability between PRO data captured between FTE-dependent and non-FTE-dependent methodologies. PMID- 26548833 TI - Ictal EEG Source Imaging for Presurgical Evaluation of Refractory Focal Epilepsy. AB - BACKGROUND: Electroencephalography source imaging (ESI) is a promising tool for localizing the cortical sources of both ictal and interictal epileptic activities. Many studies have shown the clinical usefulness of interictal ESI, but very few have investigated the utility of ictal ESI. The aim of this article is to examine the clinical usefulness of ictal ESI for epileptic focus localization in patients with refractory focal epilepsy, especially extratemporal lobe epilepsy. METHODS: Both ictal and interictal ESI were performed by the use of patient-specific realistic forward models and 3 different linear distributed inverse models. Lateralization as well as concordance between ESI-estimated focuses and single-photon emission computed tomography (SPECT) focuses were assessed. RESULTS: All the ESI focuses (both ictal and interictal) were found lateralized to the same hemisphere as ictal SPECT focuses. Lateralization results also were in agreement with the lesion sides as visualized on magnetic resonance imaging. Ictal ESI results, obtained from the best-performing inverse model, were fully concordant with the same cortical lobe as SPECT focuses, whereas the corresponding concordance rate is 87.50% in case of interictal ESI. CONCLUSIONS: Our findings show that ictal ESI gives fully lateralized and highly concordant results with ictal SPECT and may provide a cost-effective substitute for ictal SPECT. PMID- 26548834 TI - Quantitative Evaluation of Local Control and Wound Healing Following Surgery and Stereotactic Spine Radiosurgery for Spine Tumors. AB - OBJECTIVE: The present study evaluated the optimal measuring criteria to assess spinal tumor response to surgery followed by stereotactic spine radiosurgery (SRS) and reports the local control and wound complication rates following combined multimodality treatment. METHODS AND MATERIALS: Prospectively collected patient information was retrospectively reviewed to identify patients treated with spine surgery followed by SRS. Tumor sizes and volumetric assessment were formally measured. Local control status was defined according to World Health Organization (WHO, bidimensional), RECIST (unidimensional), or volumetric size change. Statistical comparative assessments of tumor measurements were performed. RESULTS: Twenty-two patients were eligible for evaluation after having undergone surgery followed by single-fraction SRS within a 2-month period. Seventeen had follow-up magnetic resonance imaging (MRI) with a mean patient follow-up of 12.59 months (range 3-36 months). None developed wound complication after radiation therapy (95% lower confidence bound 13%). Two patients had clinical recurrence while 15 of 17 achieved local control (88.3%). A test of marginal homogeneity for RECIST versus WHO was not statistically significant, P = 1.0 suggesting similar response classifications with both systems. Spearman correlations among 1) volumetric assessment, 2) bidimensional size, and 3) unidimensional size were significant for all groups (P < 0.05). CONCLUSION: High local control rates can be achieved with surgery followed by SRS. Further, adjuvant SRS following spine tumor surgery delivers less radiation to the wound than conventional radiation and thus potentially reduces wound complications. Unidimensional, bidimensional, and volumetric tumor assessments demonstrate similar results. Hence the use of the simpler RECIST criteria is suitable and appropriate for evaluating the response to treatment after spine radiosurgery. PMID- 26548835 TI - Incidence of Idiopathic Normal-Pressure Hydrocephalus in Northern Spain. AB - BACKGROUND: Although the incidence of idiopathic normal-pressure hydrocephalus (iNPH) can be 1.20 cases/1000 inhabitants/year in individuals >= 70 years old, in most series, the incidence of shunt-responsive iNPH appears to be <1/100,000 inhabitants/year. We report the results of a prospective 10-year longitudinal study of the incidence of iNPH in a northern Spanish population. METHODS: In a stable population of 590,000 inhabitants served by a single neurosurgical department, we periodically asked all primary care practitioners, neurologists, and geriatricians to refer for iNPH screening any patient with ventricular dilation who was complaining of motor disturbances, cognitive impairment, or sphincter dysfunction. RESULTS: From January 2003 to December 2012, 293 patients were referred with suspected normal-pressure hydrocephalus. In 187 patients, iNPH was diagnosed; 89 of these patients were classified as probable iNPH, and 98 were classified as possible iNPH. Cerebrospinal fluid diversion was performed in 152 patients, and 119 showed a good outcome. The incidence of iNPH was significantly greater in male patients and patients >60 years old and increased exponentially with age. After age 60, the standardized age- and sex-adjusted incidence rates for iNPH, shunt surgery for iNPH, and shunt-responsive iNPH were 13.36 cases/100,000 inhabitants/year, 10.85 cases/100,000 inhabitants/year, and 8.55 cases/100,000 inhabitants/year. No differences were detected in the response rate between probable and possible iNPH (80.52% vs. 76.00%; P = 0.497). CONCLUSIONS: Even with a protocol for patient referral in place, reported iNPH incidence was lower than predicted, reflecting a persistent problem of underdiagnosis in our population. PMID- 26548836 TI - Posterior 2-Level Vertebral Column Resection for the Treatment of Progressive Rotational Dislocation in Kyphoscoliotic Deformities. AB - OBJECTIVE: Progressive rotational dislocation of the spine is rare and surgical treatment is challenging. Few reports have described surgical decompression, fusion, and partial correction by traditional 2-stage anterior decompression and the posterior fixation technique. The goal of this retrospective study was to report a series of 6 patients with this deformity and the outcome after treatment by posterior-only 2-level vertebral column resection (PVCR). METHODS: Between 2011 and 2014, 6 patients were treated for kyphoscoliotic deformities with progressive rotational dislocation. In these 6 patients (2 males and 4 females), the diagnosis included 4 cases of congenital kyphosis and 2 cases of neurofibromatosis; the distribution of spine level was from T4 to T11; the kyphosis angle of the patients was 115 degrees (range, 107-125 degrees ); the scoliosis angle was 97 degrees (range, 80 degrees -117 degrees ); follow-up ranged from 13 to 51 months (mean, 27 months). Four patients developed progressive onset of neurologic deficit. All patients underwent surgery by 2 level PVCR for decompression and correction of kyphoscoliosis. RESULTS: Postoperatively, the patients all had different kyphosis correction rates, from 49% to 72% (mean, 63%) and scoliosis correction rates, from 57% to 78% (mean, 65%). All patients achieved successful spinal fusion with less than 3 degrees of loss of correction at the latest follow-up evaluation. The 4 patients with incomplete neurologic deficits improved 1 or 2 American Spinal Injury Association scales at follow-up of at least 6 months. CONCLUSIONS: Two-level PVCR is a safe and efficacious surgical option for the treatment of rotational dislocation in kyphoscoliosis and associated neurologic deficit. PMID- 26548837 TI - Intraventricular Meningioma: Technical Nuances in Surgical Management. AB - OBJECTIVE: Intraventricular meningiomas (IVMs) are rare tumors compared with intracranial meningiomas. Optimal surgical management of IVMs is controversial. The objective of this article was to review the outcomes and complications of meningiomas treated with various surgical approaches. METHODS: We performed a retrospective review of 18 patients with IVMs who received different treatment strategies during the period 2000-2014. Of 18 patients, 17 underwent microsurgical resection, and 1 patient received Gamma Knife radiosurgery. The literature was reviewed to compare the present cohort with previously published series. RESULTS: In our series, 12 (70%) patients underwent parieto-occipital craniotomy and a superior parietal gyrus approach, which was similar to procedures used in various series (74.4%) in the existing literature. Preoperatively, patients commonly presented with headache (65%) and neurologic deficits (70%). After surgical management, there was a significant reduction in symptoms, including headache (preoperative 65% vs. postoperative 6%, P = 0.0001), and neurologic deficits (preoperative 70% vs. postoperative 5.5%). Preoperatively, 2 patients experienced visual impairment, which was completely resolved after surgery. The Karnofsky performance scale was significantly improved after resection compared with before treatment (89 vs. 76, P = 0.003). In 4 patients with World Health Organization grade II tumor, redo surgery was required because of recurrence of tumor. CONCLUSIONS: Based on a literature review and our experience, surgical approaches for patients with IVM vary according to size, location, and laterality of the meningioma. In addition, the growth pattern of the tumor (transependymal extension), vascular supply of the tumor, and brain function (particularly visual function) can affect surgical treatment and should be identified preoperatively. PMID- 26548838 TI - IgG4 subclass glutamic acid decarboxylase antibodies (GADA) are associated with a reduced risk of developing type 1 diabetes as well as increased C-peptide levels in GADA positive gestational diabetes. AB - Some women with gestational diabetes (GDM) present with autoantibodies associated with type 1 diabetes. These are usually directed against glutamic acid decarboxylase (GADA) and suggested to predict development of type 1 diabetes. The primary aim of this study was to investigate if GADA IgG subclasses at onset of GDM could assist in predicting postpartum development. Of 1225 women diagnosed with first-time GDM only 51 were GADA-positive. Total GADA was determined using ELISA. GADA subclasses were determined with radioimmunoassay. Approximately 25% of GADA-positive women developed type 1 diabetes postpartum. Titers of total GADA were higher in women that developed type 1 diabetes (142.1 vs 74.2u/mL; p=0.04) and they also had lower titers of GADA IgG4 (index=0.01 vs 0.04; p=0.03). In conclusion we found that that women with high titers of total GADA but low titers of GADA IgG4 were more prone to develop type 1 diabetes postpartum. PMID- 26548840 TI - Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug. AB - Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3 MUg/mL. A maximum fourfold increase in solubility, reaching 53.8 MUg/mL, was observed for a solid dispersion sonicated at 19 kHz for 10 min and 475 W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility. PMID- 26548839 TI - Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40. AB - Simple and reliable methods for evaluating the inhibitory effects of drug candidates on complement activation are essential for preclinical development. Here, using an immortalized porcine aortic endothelial cell line (iPEC) as target, we evaluated the feasibility and effectiveness of an in vitro xenoantibody-mediated complement-dependent cytotoxicity (CDC) model for evaluating the complement inhibitory activity of Cp40, a potent analog of the peptidic C3 inhibitor compstatin. The binding of human xenoantibodies to iPECs led to serum dilution-dependent cell death. Pretreatment of the human serum with Cp40 almost completely inhibited the deposition of C3 fragments and C5b-9 on the cells, resulting in a dose-dependent inhibition of CDC against the iPECs. Using the same method to compare the effects of Cp40 on complement activation in humans, rhesus and cynomolgus monkeys, we found that the inhibitory patterns were similar overall. Thus, the in vitro xenoantibody-mediated CDC assay may have considerable potential for future clinical use. PMID- 26548841 TI - Sonochemical assisted synthesis of SrFe12O19 nanoparticles. AB - We present the synthesis of M-type strontium hexaferrite by sonochemistry and annealing. The effects of the sonication time and thermal energy on the crystal structure and magnetic properties of the obtained powders are presented. Strontium hexagonal ferrite (SrFe12O19) was successfully prepared by the ultrasonic cavitation (sonochemistry) of a complexed polyol solution of metallic acetates and diethylene glycol. The obtained materials were subsequently annealed at temperatures from 300 to 900 degrees C. X-ray diffraction analysis shows that the sonochemical process yields an amorphous phase containing Fe(3+), Fe(2+) and Sr(2+) ions. This amorphous phase transforms into an intermediate phase of maghemite (gamma-Fe2O3) at 300 degrees C. At 500 degrees C, the intermediate species is converted to hematite (alpha-Fe2O3) by a topotactic transition. The final product of strontium hexaferrite (SrFe12O19) is generated at 800 degrees C. The obtained strontium hexaferrite shows a magnetization of 62.3 emu/g, which is consistent with pure hexaferrite obtained by other methods, and a coercivity of 6.25 kOe, which is higher than expected for this hexaferrite. The powder morphology is composed of aggregates of rounded particles with an average particle size of 60 nm. PMID- 26548842 TI - Genetic differentiation and diversity of Callosobruchus chinensis collections from China. AB - Callosobruchus chinensis (Linnaeus) is one of the most destructive pests of leguminous seeds. Genetic differentiation and diversity analysis of 345 C. chinensis individuals from 23 geographic populations using 20 polymorphic simple sequence repeats revealed a total of 149 alleles with an average of 7.45 alleles per locus. The average Shannon's information index was 1.015. The gene flow and genetic differentiation rate values at the 20 loci ranged from 0.201 to 1.841 and 11.0-47.2%, with averages of 0.849 and 24.4%, respectively. In the 23 geographic populations, the effective number of alleles and observed heterozygosity ranged from 1.441 to 2.218 and 0.191-0.410, respectively. Shannon's information index ranged from 0.357 to 0.949, with the highest value in Hohhot and the lowest in Rudong. In all comparisons, the fixation index (F ST ) values ranged from 0.049 to 0.441 with a total F ST value of 0.254 among the 23 C. chinensis populations, indicating a moderate level of genetic differentiation and gene flow among these populations. Analysis of molecular variance revealed that the genetic variation within populations accounted for 76.7% of the total genetic variation. The genetic similarity values between populations varied from 0.617 to 0.969, whereas genetic distances varied from 0.032 to 0.483. Using unweighted pair-group method using arithmetical averages cluster analysis, the 23 geographic collections were classified into four distinct genetic groups but most of them were clustered into a single group. The pattern of the three concentrated groups from polymerase chain reactions analysis showed a somewhat different result with cluster. PMID- 26548844 TI - Novel cellular and post-genomic technologies in the treatment of glioblastoma multiforme (Review). AB - Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. The majority of modern treatment methods for GBM are not sufficiently effective with a median survival varying from 9 to 14 months. One of the main reasons for the therapeutic resistance of GBM is attributed to cancer stem cells. Pharmaceuticals that can effectively eliminate cancer stem cells do not exist. Experimentally, we have shown that cancer stem cells can be specifically affected to arrest adhesion, proliferation and migration, and other key functions. The main target of this therapy involves membrane intracellular signaling pathways of cancer stem cells that are not subject to neoplastic transformation. An effect on such a complex target requires the development of innovative biotechnological approaches. The research analysis of modern approaches towards creating biomedical drugs for treating cancer stem cells of glioblastoma multiforme is based on advances in the latest cellular and post-genomic technologies. The combination of targeted therapy with regulation of the key functions of cancer stem cells using cell systems with a remodeled proteome is suggested. PMID- 26548845 TI - Sequential changes in autophagy in diabetic cardiac fibrosis. AB - Autophagy is considered to be associated with cardiac fibrosis. However, whether autophagy accelerates or ameliorates fibrosis remains to be elucidated. In the present study, 36 rats were divided into two groups: Control rats and diabetic rats. The diabetic rats were established by feeding the animals a high fat diet combined with streptozotocin. From the two groups, six rats were sacrificed after 1, 6 and 7 months. Cardiac systolic functions were measured. The collagen volume fraction was calculated using Masson's trichome staining and the mRNA expression levels of type-I and type-III collagen were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess the levels of cardiac fibrosis. The protein contents of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62) were evaluated using western blotting, and the mRNA expression of Beclin 1 was measured using RT-qPCR, in order to assess autophagy. The results revealed that, in the diabetic rats, cardiac fibrosis developed and cardiac systolic function was reduced. In the hearts of the diabetic rats, the mRNA expression levels of collagen type I and III, and Beclin1 were upregulated; the ratio of the protein level of LC3-II/LC3-I was increased and the content of P62 was decreased. All the changes were aggravated as time increased. The changes in autophagy were correlated with those of cardiac fibrosis, suggesting that autophagy may have a synergistic role in diabetic cardiac fibrosis. PMID- 26548843 TI - Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children. AB - BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15 1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent. PMID- 26548846 TI - Giant seaperch iridovirus (GSIV) induces mitochondria-mediated cell death that is suppressed by bongkrekic acid and cycloheximide in a fish cell line. AB - Giant seaperch iridovirus (GSIV) induces cell death by an unknown mechanism. We postulated that this mechanism involves mitochondria-mediated cell death. Cell viability assays revealed a steady increase in dead grouper fin cells (GF-1) after GSIV infection, from 11% at 2 days post-infection (dpi) to 67% at 5 dpi. Annexin V/PI staining revealed GSIV infection induced apoptosis in a steadily increasing fraction of cells, from 4% at 1 dpi to 29% at 5 dpi. Furthermore, post apoptotic necrosis was apparent at 4 and 5 dpi in the late replication stage. In the early replication stage, JC-1 dye revealed mitochondrial membrane potential (DeltaPsim) loss in 42% of infected cells at 1 dpi, increasing to 98% at 3 dpi. Phosphatidylserine (PS) exposure and loss of DeltaPsim from apoptosis/necrosis was attenuated by treatment with the adenine nucleotide translocase inhibitor bongkrekic acid (BKA) and the protein synthesis inhibitor cyclohexamide (CHX). These data suggest GSIV induces GF-1 apoptotic/necrotic cell death through pathways that require newly synthesized protein and involve the mitochondrial function. PMID- 26548847 TI - [Onychomadesis: An unusual sign of alarm in the elderly]. PMID- 26548848 TI - [Traumatic spinal cord injury in people over 65 in Asturias]. AB - AIMS: to assess incidence, causes and socio-demographicaspects of traumatic spinal cord injury among patients over 65 in Asturias (Spain). PATIENTS AND METHODS: A census was performed between 1951 and 2013 of patients in Asturias, over 65 years-old coded as "traumatic spinal cord injury with or without vertebral fracture". Socio-demographic, hospital and clinical variables were recorded. RESULTS: In total 180 patients were registered, most of them males (60%), with a mean age of 73 years (maximum 91). The estimated incidence in 2010 was found to be 24.9, in 2011, 28.9 and in 2012, 32.9 cases/million/year. The distribution in the type of injury was homogeneous and location in the cervical spine (40%) was found to be more common. There was bone injury in 71.4%, with multilevel injury in more than half of the cases. The main cause was accidental fall (52.1%), mainly at own height (68.6%), and most of them located in the cervical spine (38.5%), followed by traffic accidents with 57.6% located in the cervical spine. CONCLUSIONS: A change was observed in the epidemiological profile of the patients over 65 years old with spinal cord injury. There were more cases associated with accidental fall. It is necessary to create specific preventive and therapeutic strategies for this group. PMID- 26548850 TI - Abdominal compression during endoscopy (the Bolster technique) demonstrates hidden Schatzki rings (with videos). AB - BACKGROUND AND AIMS: Schatzki rings are found in the distal esophagus, are associated with hiatal hernias, and present with intermittent dysphagia to solid foods. They can be identified by radiology (GI series or barium swallow studies) or endoscopy. Rings are not always visualized during endoscopy in patients in whom they are suspected clinically. The Bolster technique involves application of epigastric abdominal pressure, which offers the potential to reveal a Schatzki ring that is otherwise obscured within a reduced hiatal hernia. The aim of this study was to determine whether the Bolster technique improves endoscopic detection of Schatzki rings. METHODS: We reviewed 30 symptomatic patients with a history of a Schatzki ring in a tertiary care center. The Bolster technique was applied to patients in whom the ring was not visible during standard endoscopy. The main outcome measurement was identification of the Schatzki ring after the Bolster technique. RESULTS: A Schatzki ring was visible during standard endoscopy in 26 of the 30 patients. In the remaining 4, the ring was visible only after the application of the Bolster technique. CONCLUSION: The Bolster technique is a simple maneuver that can increase detection rates of Schatzki rings during endoscopy. PMID- 26548849 TI - Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study. AB - BACKGROUND AND AIMS: The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS: This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS: A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150 493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS: TPD has no benefit on treatment outcomes in patients undergoing EUS guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs. PMID- 26548851 TI - Adaptive simulation training using cumulative sum: a randomized prospective trial. AB - BACKGROUND: Cumulative sum (Cusum) is a novel tool that can facilitate adaptive, individualized training curricula. The purpose of this study was to use Cusum to streamline simulation-based training. METHODS: Preclinical medical students were randomized to Cusum or control arms and practiced suturing, intubation, and central venous catheterization in simulation. Control participants practiced between 8 and 9 hours each. Cusum participants practiced until Cusum proficient in all tasks. Group comparisons of blinded post-test evaluations were performed using Wilcoxon rank sum. RESULTS: Forty-eight participants completed the study. Average post-test composite score was 92.1% for Cusum and 93.5% for control (P = .71). Cusum participants practiced 19% fewer hours than control group participants (7.12 vs 8.75 hours, P < .001). Cusum detected proficiency relapses during practice among 7 (29%) participants for suturing and 10 (40%) for intubation. CONCLUSIONS: In this comparison between adaptive and volume-based curricula in surgical training, Cusum promoted more efficient time utilization while maintaining excellent results. PMID- 26548852 TI - TRAF6-mediated degradation of DOK3 is required for production of IL-6 and TNFalpha in TLR9 signaling. AB - Our previous study showed that the downstream of kinase 3 (DOK3) is degraded during macrophage stimulation with CpG. However, the underlying mechanism and role in Toll-like receptor 9 (TLR9) signaling remains elusive. In this study, we demonstrate that CpG treatment leads to ubiquitin-mediated degradation of DOK3 via interaction with an E3 ligase TNFR-associated factor 6 (TRAF6). We also identified the 27th amino acid (lysine) of DOK3 is responsible for Ly48 polyubiquitination of DOK3. Furthermore, reintroduction of DOK3 (K27R) into DOK3 deficient macrophages abolishes DOK3 degradation induced by CpG and suppresses the production of IL-6 and TNFalpha. More importantly, our study uncovers a novel role of an E3 ligase TRAF6, namely, TRAF6 is also able to catalyse Lys 48 polyubiquitylation of target protein except for Lys 63 polyubiquitylation. PMID- 26548853 TI - Screening Mammography: Update and Review of Publications Since Our Report in the New England Journal of Medicine on the Magnitude of the Problem in the United States. PMID- 26548854 TI - ECG-gated Versus Non-ECG-gated High-pitch Dual-source CT for Whole Body CT Angiography (CTA). AB - RATIONALE AND OBJECTIVES: To investigate motion artifacts, image quality, and practical differences in electrocardiographic (ECG)-gated versus non-ECG-gated high-pitch dual-source computed tomography angiography (CTA) of the whole aorta. MATERIALS AND METHODS: Two groups, each including 40 patients, underwent either ECG-gated or non-ECG-gated high-pitch dual-source CTA of the whole aorta. The aortic annulus, aortic valve, coronary ostia, and the presence of motion artifacts of the thoracic aorta as well as vascular contrast down to the femoral arteries were independently assessed by two readers. Additional objective parameters including image noise and signal-to-noise ratio were analyzed. RESULTS: Subjective and objective scoring revealed no presence of motional artifacts regardless of whether the ECG-gated or the non-ECG-gated protocol was used (P > 0.1). Image acquisition parameters (examination length, examination duration, radiation dose) were comparable between the two groups without significant differences. The aortic annulus, aortic valve, and coronary ostia were reliably evaluable in all patients. Vascular contrast was rated excellent in both groups. CONCLUSIONS: High-pitch dual-source CTA of the whole aorta is a robust and dose-efficient examination strategy for the evaluation of aortic pathologies whether or not ECG gating is used. PMID- 26548855 TI - Measurements of Hepatic Metastasis on MR Imaging:: Assessment of Interobserver and Intersequence Variability. AB - RATIONALE AND OBJECTIVES: The purpose of the study was to investigate interobserver and intersequence variability in the measurement of hepatic metastasis on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study was conducted with an institutional review board-approved waiver of informed consent and was in compliance with the Health Insurance Portability and Accountability Act. We searched medical records at our institution for patients with histologically proven metastases to the liver who had undergone MRI from January 2008 to June 2010. We identified 20 patients with 30 measurable liver lesions. The liver lesions were measured on five different MRI sequences. A presenter radiologist selected and localized all metastatic lesions considered to be measurable according to the Response Evaluation Criteria in Solid Tumors, and these lesions were measured (Eisenhauer et al., 2009) by three radiologists independently. We calculated lesion-wise intraclass correlation coefficients (ICCs) to estimate interobserver and intersequence agreement in lesion diameter measurement. A Bland-Altman plot was used to estimate the limits of agreement between radiologists and MRI sequences. RESULTS: There were 30 metastases, and almost all of which had regular and well-defined margins. Interobserver ICCs were greater than 0.95 for different MRI sequences except for the measurements in apparent diffusion coefficient images. Intersequence ICCs were greater than 0.92. Bland-Altman plots between physicians confirmed that reader measurements were closely tied together, with small differences in means. CONCLUSIONS: MRI can reproducibly measure hepatic metastatic lesions without significant variability among interpreting radiologists or among MRI sequences, and is thus a reliable method for assessing the size of hepatic metastasis. PMID- 26548856 TI - Cumulative effects of repetitive intermittent hypercapnic hypoxia on orexin in the developing piglet hypothalamus. AB - Orexin neuropeptides (OxA and OxB) and their receptors (OX1R and OX2R) are involved in maintenance of sleep and wakefulness, and are regulated by various environmental stimuli. We studied piglets, in the early neonatal period, exposed to 48-min of intermittent hypercapnic hypoxia (IHH; 7% O2/8% CO2) alternating with air. Three groups of 13-14 day-old piglets with IHH exposure of 1-day (1D IHH) (n=7), 2-days (2D-IHH) (n=7) and 4-days (4D-IHH) (n=8) were compared to controls (exposed only to air, n=8). Immunoreactivity of OxA and OxB was studied in the piglet hypothalamic regions of the dorsomedial hypothalamus (DMH), perifornical area (PeF) and lateral hypothalamic area (LH). Results showed that after 1D- and 2D-IHH, total OxA and OxB expression decreased by 20% (p <= 0.005) and 40% (p<0.001), respectively. After 4D-IHH, the decrease in OxA and OxB was 50% (p<0.001). These findings indicate that a chronic IHH exposure induces greater changes in orexin neuropeptide expression than an acute 1-day exposure in the hypothalamus. This may be causally related to the dysregulation of sleep. PMID- 26548857 TI - High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides. AB - Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases. PMID- 26548859 TI - The clinical profile of women with stable ischaemic heart disease in Spain. More effort is needed in secondary prevention. SIRENA study. AB - OBJECTIVES: Cardiovascular diseases are the leading cause of death for women, especially ischaemic heart disease, which is still considered a man's disease. In Spain, there are various registries on ischaemic heart disease, although none are exclusively for women. The objectives of the SIRENA study were to describe the clinical profile of women with ischaemic heart disease treated in cardiology consultations, to estimate its prevalence of cardiovascular risk factors and understand its clinical management. PATIENTS AND METHODS: A multicentre observational study was conducted with a sample of 631 women with stable ischaemic heart disease, consecutively included during cardiology consultations. Forty-one researchers from all over Spain participated in the study. RESULTS: The mean age was 68.5 years. The clinical presentation was in the form of acute coronary syndrome in up to 67.2% of the patients. The prevalence of cardiovascular risk factors was high (77.7% of the patients had hypertension, 40.7% had diabetes and 68% had dyslipidaemia), with 30.7% having uncontrolled hypertension, 78.4% having LDL-cholesterol levels higher than 70mg/dL and 49.2% having HbA1c levels greater than 7%. The considerable majority of the patients underwent optimal medical treatment with antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers and hypolipidaemic agents. Coronary angiography was performed for 88.3% of the patients, and 63.4% underwent percutaneous coronary intervention. CONCLUSIONS: Women with stable ischaemic heart disease in Spain initially present some form of acute coronary syndrome and a high prevalence of inadequately controlled cardiovascular risk factors, despite undergoing optimal medical therapy. A high percentage of these women undergo coronary revascularisation. Increased efforts are required for secondary prevention in women with stable ischaemic heart disease. PMID- 26548860 TI - The Structural Alteration and Aggregation of Bovine Lens Gamma-Crystallin by Homocysteinylation; The Pathomechanism Underlying Cataract Development During Hyperhomocysteinimia. AB - A significant association between increased level of blood homocysteine (hyperhomocysteinimia) and various eye pathological disorders including cataract has been reported. This metabolic byproduct is converted into a highly reactive cyclic thioester compound, homocysteine thiolactone (HCTL), which can potentially react with free amino groups in protein. In the current study, as bovine lens gamma-Crystallin (gamma-Cry) was incubated with HCTL, various spectroscopic techniques, gel mobility shift assay, and microscopic analysis were applied to characterize structural variation and aggregation of this protein. According to the fluorescence results, HCTL-induced structural alteration was accompanied with the significant enhancement in surface hydrophobicity of gamma-Cry. Also, this cyclic thioester was indicated to alter gamma-Cry secondary structures and to induce aggregation of this protein. The results of gel mobility shift assay suggest the involvement of disulfide bond cross-linking in formation of the protein aggregates. In conjunction with Thioflavin T and Congo red assays, the microscopic analysis also suggests that HCTL can induce formation of ordered aggregate entities in bovine lens gamma-Cry. The relationship between gamma-Cry insolubilization/aggregation and growth of cataract disorders has been already reported. Therefore, the induction of structural alteration and aggregation of gamma-Cry by HCTL can elucidate the pathomechanism underlying cataract disorders particularly in hyperhomocysteinimia. PMID- 26548861 TI - Human Peroxiredoxins 1 and 2 and Their Interacting Protein Partners; Through Structure Toward Functions of Biological Complexes. AB - Since their discovery in the mid-nineties, peroxiredoxins have drawn much attention and the number of papers publications on different Prxs has been multiplied. The rise in interest in this topic is probably due, at least in part, to the large and further increasing functions attributed to the members of this family of ubiquitous proteins, including many redox and non-redox physiological functions. This review presents a Since their discovery in the mid-nineties, peroxiredoxins have drawn much attention and the number of publications on different Prxs has been multiplied. The rise in interest in this topic is probably due, at least in part, to the large and further increasing functions attributed to the members of this family of ubiquitous proteins, including many redox and non-redox physiological functions. This review presents a literature survey of the protein partners of the human Peroxiredoxin-1 and Peroxiredoxin- 2 of the Peroxiredoxin 1 subfamily, the most abundant class. Three sequence motifs, or combinations thereof, were found in the protein partners, namely, CXXC, PXXP, and LXXLL. These findings are discussed in light of i) protein partner localization, function and biological pathways and ii) the peroxiredoxins regions important for partner interaction, as revealed by the Peroxiredoxin-1 Sulfiredoxin-1 complex structure. The outcome of these analyses is expected to unravel some common molecular bases underlying peroxiredoxins propensity to bind a partner, as well as to propose a functional role for this interaction that could help to widen the biological role of this important class of enzymes. PMID- 26548862 TI - In Vitro Reconstitution of the Toll/Interleukin-1 Receptor (TIR) Domain Complex Between TLR5/6 and Myd88. AB - Toll-like receptors (TLRs) are evolutionarily conserved receptors with trimodular structure to respond to endogenous ligands and exogenous ligands from microbial pathogens. The highly conserved cytoplasmic C-terminal Toll/interleukin-1 receptor (TIR) domain of TLRs plays a crucial role in inflammatory reactions. In myeloid differentiation primary-response protein 88 (MyD88)- dependent signaling pathway, the interaction of TLRsTIR with cytosolic adaptor protein, MyD88TIR recruits IL-1R-associated kinases (IRAK) for subsequent activation of transcription factors nuclear factor kB (NF-kB) and activation protein 1 (AP-1) and other effector molecules. In the present investigation, TLR5TIR, TLR6TIR and MyD88TIR genes were subcloned and overexpressed in bacterium Escherichia coli strain BL- 21 (DE3). The purification and biochemical characterization of TLR5TIR and TLR6TIR&, and MyD88TIR proteins were also performed. The protein-protein interactions between TIR domains of TLR5 and TLR6 with MyD88, respectively, were evaluated in vitro at physiological pH and salt concentration. The in vitro reconstitution results showed that under physiological pH and salt concentration, MyD88TIR interacted with TLR5TIR, and did not interact with TLR6TIR protein. Both TIR domain-containing TLR5 and TLR6 proteins were prone to aggregation in a temperature-dependent manner at room temperature. At normal physiological pH and salt concentration, with the addition of binding partner MyD88TIR to TLR5/6TIR, time-dependent aggregation was not observed in both TLRsTIR at both room temperature and 4 oC for 2 d, influencing the solubility of TLR5/6TIR. Moreover, TLR5TIR alone exhibited increase in solubility of the protein with increase in the salt concentration of the buffered solution from 0.025 M to 1.25 M at room temperature. PMID- 26548863 TI - Comparative Protein Profiling of Intraphagosomal Expressed Proteins of Mycobacterium bovis BCG. AB - BCG, the only available vaccine against tuberculosis affords a variable protection which wanes with time. In this study we have analyzed and compared the proteins which are expressed differentially during broth-culture and intraphagosomal growth of M.bovis BCG. Eight proteins which showed increased expression during the intraphagosomal growth were identified by MALDI-TOF/MS. These were - a precursor of alanine and proline-rich secreted protein apa, isoforms of malate dehydrogenase, large subunit alpha (Alpha-ETF) of electron transfer flavoprotein, immunogenic protein MPB64 precursor, UPF0036 protein, and two proteins with unknown function. Based on these findings we speculate that higher expression of these proteins has a probable role in intracellular survival, adaptation and/or immunoprotective effect of BCG. Further, these proteins might also be used as gene expression markers for endosome trafficking events of BCG. PMID- 26548864 TI - Recombinant Human Semenogelin-1 (Sg1) and Sg1 (1-159) form Detergent Stable Amyloid like Aggregates in vitro. AB - Senile seminal vesicle amyloidosis (SSVA) is associated with deposition of semenogelin-1 (Sg1) protein aggregates in seminal vesicles that may manifest as hematospermia. Sg1 is the predominant protein that entraps spermatozoa which are freed upon fragmentation of Sg1 by the protease prostate specific antigen (PSA), post semen release. Certain small peptide fragments of Sg1 have been reported to form amyloid aggregates in vitro that can enhance HIV infectivity to cell cultures. However, the amyloid deposits in the seminal vesicles are expected to be that of the full length Sg1, as PSA is encountered downstream. So far, amyloid forming ability of full length Sg1 has not been established in vitro. Here, we examined the amyloidogenicity of full length Sg1 and a large fragment Sg1 (1 159), using recombinant proteins and tested if Zinc has any effect on their aggregation. Levels of Zinc, which is essential for health of male reproductive system, gradually decline with age. We succeeded in forming amyloid-like aggregates of Sg1 full length and Sg1 (1-159) fragment showing detergent stability and found that presence of Zn2+ substantially inhibits their amyloid aggregation in vitro. Possibly, high Zn2+ found in seminal plasma of young individuals may have preventive role against aggregation of Sg1 in seminal vesicles. PMID- 26548865 TI - Activation of Mitochondrial Uncoupling Protein 4 and ATP-Sensitive Potassium Channel Cumulatively Decreases Superoxide Production in Insect Mitochondria. AB - It has been evidenced that mitochondrial uncoupling protein 4 (UCP4) and ATP regulated potassium channel (mKATP channel) of insect Gromphadorhina coqereliana mitochondria decrease superoxide anion production. We elucidated whether the two energy-dissipating systems work together on a modulation of superoxide level in cockroach mitochondria. Our data show that the simultaneous activation of UCP4 by palmitic acid and mKATP channel by pinacidil revealed a cumulative effect on weakening mitochondrial superoxide formation. The inhibition of UCP4 by GTP (and/or ATP) and mKATP channel by ATP elevated superoxide production. These results suggest a functional cooperation of both energy-dissipating systems in protection against oxidative stress in insects. PMID- 26548866 TI - Critical role of miR-155/FoxO1/ROS axis in the regulation of non-small cell lung carcinomas. AB - Lung cancer is the leading cause of cancer-related deaths in the world, and non small cell lung carcinomas (NSCLC) account for 85 % of lung cancer cases. Despite enormous achievement in the treatment of NSCLC, the molecular mechanisms underlying the pathogenesis are largely unknown. The current study was designed to evaluate the role of miR-155 in NSCLC cell proliferation and to explore the possible molecular mechanisms. We found that miR-155 expression was increased in NSCLC tissues and cell lines. The increase of miR-155 significantly increased A549 cell proliferation, decreased S phase cell population and increased G2/M phase cell population. Decrease of miR-155 expression markedly inhibited cell proliferation, increased S phase cell population, and decreased G2/M phase cell population. Increase of miR-155 significantly decreased forkhead box protein O1 (FoxO1) 3'UTR luciferase activity and expression and decrease of miR-155 notably increased FoxO1 expression. Overexpression of FoxO1 significantly inhibited miR 155-exerted increase of cell proliferation and G2/M cell population. Downregulation of FoxO1 by siRNAs significantly promoted cell proliferation, decreased S phase cell numbers, and increased G2/M cell population. Downregulation of FoxO1 markedly increased ROS level, as reflected by increased DHE staining. Moreover, when N-acetylcysteine was present, increase of cell proliferation induced by downregulation of FoxO1, and upregulation of miR-155 was significantly inhibited. In conclusion, we found that miR-155 promoted NSCLC cell proliferation through inhibition of FoxO1 and the subsequent increase of ROS generation. Our findings highlight miR-155/FoxO1/ROS axis as a novel therapeutic target for the inhibition of NSCLC growth. PMID- 26548867 TI - The Role of Aging and Disability Resource Centers in Serving Adults Aging with Intellectual Disabilities and Their Families: Findings from Seven States. AB - For the first time, adults with intellectual and developmental disabilities (I/DD) are living to experience old age. The purpose of this project was to assess the activities of aging and disability resource centers (ADRCs) as they seek to serve older adults with intellectual disabilities and their family caregivers. Data come from 21 in-depth qualitative interviews with ADRC staff in seven states. Results of this qualitative analysis indicate that ADRCs are not focusing explicitly on adults aging with I/DD and their family caregivers, but meeting the needs of this population is a future goal of ADRCs. Challenges related to accessing and providing information and referral services for adults aging with I/DD were described and highlight existing unmet needs of this population. Supporting adults who simultaneously require aging and disability services requires true coordination of aging and disability service systems. PMID- 26548868 TI - Magnetic resonance enterography is feasible and reliable in multicenter clinical trials in patients with Crohn's disease, and may help select subjects with active inflammation. AB - BACKGROUND: Reliable tools for patient selection are critical for clinical drug trials. AIM: To evaluate a consensus-based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials. METHODS: This study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150-220 (n = 4); 220-450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14-day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES-CD). RESULTS: 37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test-retest and inter-reader reliability scores. The MaRIA scores for the terminal ileum had excellent test-retest and inter-reader reliability, with correlations >0.9. The proximal ileum showed strong within-reader agreement (0.90 0.96), and fair between-reader agreement (0.59-0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES-CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra-abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%. CONCLUSIONS: Magnetic resonance enterography of high-quality and reproducibility was feasible in a global multi- centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials. PMID- 26548869 TI - Physicomechanical characterization of polyetheretherketone and current esthetic dental CAD/CAM polymers after aging in different storage media. AB - STATEMENT OF PROBLEM: Polyetheretherketone (PEEK) can be used to support fixed dental prostheses. However, information about physicomechanical characterization is still scarce. PURPOSE: The purpose of this in vitro study was to assess effects of different aging regimens/durations on roughness, solubility, water absorption, Martens hardness (HM), and indentation modulus/EIT on different computer-aided design and computer-aided manufacturing (CAD/CAM) polymers. MATERIAL AND METHODS: Forty standardized specimens of the following materials were fabricated: PEEK: Dentokeep (DK); hybrid material: VITA Enamic (EN); composite resins: LAVA Ultimate (LU) and an experimental CAD/CAM nanohybrid composite resin (EX); poly(methyl methacrylate) (PMMA)-based: VITA CAD-Temp (CT); Telio CAD (TC), artBloc Temp (AT), and ZENOTEC ProFix (ZP). A nanofilled-polymer for interim restorations, Protemp 4 (CG), served as the control group. Specimens were stored in sodium chloride, artificial saliva, physiological saliva, and distilled water at 37 degrees C for 1, 7, 14, 28, 90, and 180 days. Roughness, water absorption, HM, and EIT were investigated after each storage period; solubility was determined after 180 days only. Data were analyzed using weighted 3/2/1-way ANOVA and the post hoc Scheffe tests (alpha=.05). RESULTS: Storage media had no effect on surface roughness and water absorption. Physiological saliva revealed the highest significant impact on solubility followed by artificial saliva, sodium chloride, and distilled water. Water absorption increased significantly with storage duration. PEEK showed the lowest solubility and water absorption values. The highest solubility was observed for the conventional polymer CG, and the highest water absorption was found for the composite LU. PMMA-based TC, ZP, CG, and AT showed the lowest HM and indentation modulus, followed by CT, and PEEK. The highest values were observed for the hybrid material EN, followed by LU and EX. CONCLUSIONS: The hardness parameters of PEEK were comparable with those of PMMA-based materials. PMID- 26548870 TI - Influence of stress corrosion on the mechanical properties of laser-welded titanium. AB - STATEMENT OF PROBLEM: Whether laser-welded (LW) titanium can resist the stress corrosion produced by the combination of fluoride ions and stress in the oral environment is unknown. PURPOSE: The purpose of this in vitro study was to investigate the influence of stress corrosion on the mechanical properties of LW titanium. MATERIAL AND METHODS: Twenty-seven titanium bars (25*2 mm) with a circular cross-section were cut in half and laser-welded, while another 27 nonwelded (NW) bars were used as the control. Thirty bars were submitted to a flexural load of 480 N at 1 Hz and immersed in artificial saliva at pH 6 (S1) or in 1000 ppm fluoride-containing saliva at pH 6.0 (S2) or 2.0 (S3) at room temperature for up to 4000 cycles. After the stress corrosion simulation, the tensile strength and Vickers microhardness were determined (n=5). Twelve LW and NW bars were submitted to the corrosion immersion test media for 51 days (n=2) to determine polarization curves (n=2) in an artificial saliva media. The corroded surface was examined with scanning electron microscopy (SEM). RESULTS: The combination of fluoride and low pH significantly decreased the tensile strength of LW (P<.05). Stress corrosion did not affect the hardness of LW or NW (P>.05). NW bars immersed in S3 exhibited progressive surface dissolution, while LW bars spontaneously fractured at the welded area after 25 days of immersion in the same medium. SEM images demonstrated pitting corrosion without the presence of cracks in both groups immersed in S3. CONCLUSIONS: Stress corrosion caused by acidic fluoride-containing saliva and flexural load cycling decreased the tensile strength and hardness of LW titanium bars. PMID- 26548871 TI - Effect of remaining tooth structure on the fracture resistance of endodontically treated maxillary premolars: An in vitro study. AB - STATEMENT OF PROBLEM: Assessing the quantity and distribution of residual coronal dentin is important in deciding the restorability of endodontically treated teeth. PURPOSE: The purpose of this in vitro study was to investigate the relationship between the cross-sectional area and location of remaining coronal tooth structure and the fracture resistance of restored teeth after endodontic treatment. MATERIAL AND METHODS: Fifty-five extracted maxillary premolars received endodontic treatment and crown preparations. The teeth were assigned to 11 groups of 5 teeth according to the number and the location of missing axial walls. Impressions of the prepared teeth were made to fabricate dies. Each die was sectioned 1 mm above the finish line, and the dentin surface area was measured. All teeth were restored with composite resin cores and cast metal crowns. The specimens were thermocycled between 5 degrees C and 55 degrees C for 500 cycles before loading until failure with a universal testing machine. The results were analyzed with 1-way ANOVA and post hoc comparisons. RESULTS: Specimens with all axial walls intact around the access cavity had the highest mean fracture strength (1380.5 +/-393.9 N). Groups with the palatal and 1 or 2 proximal walls missing showed the lowest mean failure loads (398.4 N +/-149.5 N and 344.7 N +/-91.2 N). The correlation between the surface area and the fracture resistance was 0.72 CONCLUSIONS: For restored endodontically treated maxillary premolars, a positive linear relationship was found between the remaining coronal dentin surface area and fracture strength. Residual dentin location influences fracture resistance. PMID- 26548872 TI - Is there a potential for durable adhesion to zirconia restorations? A systematic review. AB - STATEMENT OF PROBLEM: With a number of zirconia ceramic materials currently available for clinical use, an overview of the scientific literature on the adhesion methods and their potential influence is indicated. PURPOSE: The purpose of this systematic review was to classify and analyze the existing methods and materials proposed to improve adhesion to zirconia surfaces. MATERIAL AND METHODS: The current literature of in vitro studies examining the bond strength on zirconia ceramics, including clinical studies from 1998 until 2014, was analyzed. A search of the English language literature was undertaken using MEDLINE and PubMed, and a hand search was made for any relevant research paper from the library of a dental school. Papers evaluating only alumina restoration bond or ceramic-zirconia bond were excluded. RESULTS: A total of 134 publications were identified for analysis. Different adhesive techniques with different testing methods were reviewed. Results were difficult to compare in that the parameters varied in each research protocol. CONCLUSIONS: Airborne-particle abrasion and tribochemical silica coating are reference pretreatment methods. Adhesive monomers are necessary for chemical bonding. Surface contamination and aging have negative effects on adhesion to zirconia. Many factors influence each combination of zirconia material, such as surface treatment, adhesive medium, and aging conditions. Laboratory studies should be confirmed by clinical trials. PMID- 26548873 TI - Retention of bonded titanium copings fixed to implant abutments. AB - STATEMENT OF PROBLEM: Conical abutments can be laser welded to the abutment base to compensate for differing implant axes. As laser welding requires expensive equipment, alternative methods for bonding the conical abutment part with the abutment base should be considered. PURPOSE: The purpose of this in vitro study was to evaluate the retention of Ti-6Al-7Nb copings bonded adhesively to Ti-6Al 7Nb abutments and to compare it with the stability achieved by laser welding. MATERIAL AND METHODS: A total of 104 two-part Ti-6Al-7Nb specimens were prepared and divided into 13 groups with 8 specimens each. In this 2-part study, 3 luting resins (Panavia F 2.0 [PF]; Multilink Automix [MA]; Superbond C&B [SB]) were used with or without metal priming (PR). The laser welding group (LW) served as the control. After storage for 1 or 150 days (150 days with thermal cycling [TC]), push-out retention and welded joint stability were tested. The data were analyzed with ANOVA and the Tukey HSD multiple comparison tests. RESULTS: The choice of resin, thermal cycling, and metal priming had a significant effect on resin push out retention. LW provided the strongest retention, followed by PF, MA, and SB. For PF and SB, TC decreased retention. PR did not lead to higher retention but provided better bonding stability when TC was applied. CONCLUSIONS: The retention values suggest that considering the maximum mastication forces, resin bonding is an appropriate substitute for the laser welding method. PMID- 26548874 TI - Gingival pigmentation by Ni-Cr-based metal ceramic crowns: A clinical report. AB - This clinical report describes treatment of a patient with gingival pigmentation after the restoration of the right maxillary canine and first premolar with Ni-Cr based metal ceramic crowns and investigation of mechanisms of gingival discoloration. Histopathological observation and energy dispersive x-ray spectroscopy analysis of the retrieved pigmented gingiva revealed brown deposits both in the epithelial cells and along the basement membranes but no trace of Ni or Cr elements in the pigmented particles, indicating that the gingival pigmentation adjacent to the Ni-Cr-based metal ceramic prosthesis may not be caused by direct deposition of the released ions. PMID- 26548875 TI - Color change of soft silicone relining materials after storage in artificial saliva. AB - STATEMENT OF PROBLEM: The interaction between artificial saliva and color change of silicone soft liners has not been clarified. PURPOSE: The purpose of this in vitro study was to investigate the effect of artificial saliva storage on the color stability of soft silicone liners. MATERIAL AND METHODS: Four silicone based liners (Elite Soft Relining, GC Reline Soft, Megabase, and Mucopren Soft) (n=10) were tested after 7, 30, and 90 days of storage in artificial saliva at 37 degrees C in darkness. The color of each specimen was measured with a spectrophotometer using the CIELab color scale. Statistical analysis was performed with the nonparametric ANOVA for dependent variables and nonparametric ANOVA for independent variables (alpha=.05). RESULTS: The storage in artificial saliva significantly affected the color integrity of 3 of the 4 tested materials. For GC Reline Soft material, the time of storage had no significant effect on color. CONCLUSIONS: Significant differences were found in the color changes of silicone-based denture liners after storage in artificial saliva. With regard to color stability, GC Reline Soft may be recommended for use in dental practices as a silicone soft relining material for long-term applications. PMID- 26548876 TI - Comparison of two color-difference formulas using the Bland-Altman approach based on natural tooth color space. AB - STATEMENT OF PROBLEM: Several formulas to measure color differences have been proposed to improve the correlation between color measurements and visual perception. Despite the progress obtained, equating between formulas is complex, rendering the exchange of information in scientific papers difficult. PURPOSE: The purpose of this study was to determine the relationship between the results provided by classic CIELab (DeltaEab*) and the CIEDE2000 (DeltaE00) formulas in the natural tooth color space using the Bland and Altman limits of agreement, to use this relationship to establish the equivalences between the tooth color thresholds of acceptability and perceptibility of both formulas, and to evaluate whether the relationship between DeltaEab* and DeltaE00 is modified depending on the axis on which the changes occur. MATERIAL AND METHODS: The L*, a*, and b* means coordinates in the 26 shade tabs of the Toothguide 3D Master were used, and color differences were calculated in 325 pairs of shade tabs using the CIELab (DeltaE*ab) and CIEDE2000 (DeltaE00) color difference formulas. The results obtained with these formulas were compared, and the limits of agreement after a logarithmic transformation of the data were obtained. RESULTS: The linear relationship between both formulas was DeltaE00 =0.66DeltaE*ab. The results obtained with the CIELab formula were between 1.15 (95% confidence interval 1.11 to 1.18) and 2.09 (95% confidence interval 2.03 to 2.15) times higher than those obtained with the CIEDE2000 formula. CONCLUSIONS: In the natural tooth color space, the scale factor between CIEDE2000 and CIELab values changes from 0.46 to 0.90, such that providing an accurate scale factor between both values is difficult. Furthermore, the DeltaE00/DeltaE*ab ratio increases with the increase in DeltaL* and the decrease in Deltab*. The pairs for which the ratio is highest are those in which the difference in color is mainly due to changes in lightness, whereas the pairs for which the ratio is the smallest are those in which the difference in color is mainly due to changes on the blue-yellow axis. PMID- 26548877 TI - Positioning handle and occlusal locks for the Teeth-in-a-Day protocol. AB - Positioning handles and occlusal locks have evolved as improvements to the Teeth in-a-Day protocol. These improvements have enabled a more accurate alignment of the removable dental prosthesis during the conversion prosthesis technique. These improvements can be easily incorporated through computer-aided design and computer-aided manufacturing digital denture fabrication process. PMID- 26548878 TI - Effect of implant number and distribution on load transfer in implant-supported partial fixed dental prostheses for the anterior maxilla: A photoelastic stress analysis study. AB - STATEMENT OF PROBLEM: The 4-, 3- or even 2-implant-supported partial fixed dental prosthesis (PFDP) designs have been used to rehabilitate the anterior edentulous maxilla. PURPOSE: The purpose of this in vitro study was to compare the stress distribution in the supporting tissues surrounding implants placed in the anterior maxilla with 5 PFDP designs. MATERIAL AND METHODS: A photoelastic model of the human maxilla with an anterior edentulous region was made with photoelastic resin (PL-2; Vishay Micro-Measurements), and 6 straight implants (OsseoSpeed; Astra Tech AB) were placed in the 6 anterior tooth positions. The 5 design concepts based on implant location were as follows: model 6I: 6 implants; model 2C2CI: 4 implants (2 canines and 2 central incisors); model 2C2LI: 4 implants (2 canines and 2 lateral incisors); model 2C1CI: 3 implants (2 canines and 1 central incisor); and model 2C: 2 canines. A load of 127.4 N was applied on the cingulum of 3 teeth at a 30-degree angle to the long axis of the implant. Stresses that developed in the supporting structure were recorded photographically. RESULTS: The 6-implant-supported PFDP exhibited the most even and lowest distribution of stresses in all loading conditions. When the canine was loaded, the 2- or 3-implant-supported PFDP showed higher stresses around the implant at the canine position than did the 4- or 6-implant-supported PFDP. When the central incisor or lateral incisor was loaded, the two 4-implant-supported PFDPs exhibited similar levels of stresses around the implants and showed lower stresses than did the 2- or 3-implant-supported PFDP. CONCLUSIONS: Implant number and distribution influenced stress distribution around the implants in the anterior maxilla. With a decrease in implant number, the stresses around the implants increased. PMID- 26548879 TI - Crossover clinical trial of different methods of removing a denture adhesive and the influence on the oral microbiota. AB - STATEMENT OF PROBLEM: The difficulty of removing denture adhesive is a common problem reported by users of these products. PURPOSE: The purpose of this clinical study was to investigate the effectiveness of different cleaning protocols for removing a denture adhesive (DA) and the influence on the oral microbiota. MATERIAL AND METHODS: Twenty participants wearing well-fitting complete dentures were instructed to use a denture adhesive 3 times a day during a 4-week trial, divided into 4 stages: (A) control-3 daily denture brushings using water at ambient temperature, (B)-3 daily denture brushings using water at ambient temperature plus coconut soap, (C)-3 daily denture brushings using water at ambient temperature plus dentifrice; (D)-3 daily denture brushings using water at ambient temperature combined with immersion in sodium perborate solution for 5 minutes before nocturnal sleep. After each 1-week stage, saliva specimens were collected. A dye was used to display and quantify the remaining DA on the internal surface of the maxillary dentures as a percentage. For microbiological analysis, the saliva was diluted and plated onto Petri dishes containing a nonselective culture medium and Candida spp culture media. After the incubation period, Candida species were identified and the number of colony forming units (CFU/mL) was calculated. RESULTS: A significant difference was found among the 4 cleaning methods for the quantification of remaining DA (Friedman, P=.036). Brushing the dentures with coconut soap, dentifrice, or water combined with immersion in sodium perborate solution was more effective in removing DA than brushing with only water. The cleaning methods did not influence the quantification of microorganisms in general or Candida albicans and other Candida species in particular. CONCLUSIONS: Brushing the dentures with coconut soap, dentifrice, or water combined with immersion in sodium perborate solution was more effective for removing cream-type denture adhesive than brushing with only water. PMID- 26548880 TI - Influence of interimplant distance on the crestal bone height around dental implants: A systematic review and meta-analysis. AB - STATEMENT OF PROBLEM: Indexed publications lack a systematic review and meta analysis of the influence of interimplant distance on the interproximal crestal bone height (ICBH) around implants. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the influence of interimplant distance on ICBH around implants. MATERIAL AND METHODS: The question addressed was, "Does interimplant distance influence the ICBH around implants?" Indexed databases from 1978 up to April 2015 were searched by using the keywords "crestal bone level", "bone loss", "bone height", and "interimplant distance." Reference lists of potentially relevant original and review articles were searched manually to identify any unidentified studies. Articles available online in electronic form ahead of print were eligible for inclusion. Letters to the Editor, case reports, case series, commentaries, studies involving bone augmentation procedures, and studies published in languages other than English were excluded. A meta-analysis of mean differences in ICBH among study groups was also performed. RESULTS: In total, 5 animal studies with relatively short follow-up periods (2-12 months) were included. Results from 4 studies showed no significant differences in ICBH around implants placed 1 to 3 mm apart. However, 1 of the 5 studies found that vertical bone loss was significantly lower in implants that had an interimplant distance of 5 mm than those placed at a distance of 1 mm. Platform switched and rough surface implants were used in all studies. CONCLUSIONS: The influence of interimplant distance on ICBH around dental implants remains unclear. PMID- 26548881 TI - Direct method of registering periimplant soft tissue forms for implant-supported fixed dental prostheses. AB - This article describes a direct technique for communicating implant abutment and pontic intaglio surface forms with the dental laboratory. The technique uses a matrix and a screw-retained custom interim restoration. The matrix is used to transfer the interim restoration and periimplant tissue forms from the patient's mouth to an implant position-verified cast. After being connected to this cast, a silicone soft tissue replicating material is injected into the matrix. The result is a definitive cast with accurate implant position and soft tissue forms. PMID- 26548882 TI - Management of restricted mouth opening caused by radiation: A clinical report. AB - Trismus, a commonly observed sequela in patients who have undergone radiation therapy to treat malignancies of the head and neck, causes a loss of function that reduces patients' overall quality of life. Radiation can cause intense fibrosis in the masticatory muscles, and this fibrosis may lead to trismus. This clinical report describes the management of a patient with radiation-induced trismus who was treated with a custom-made mouth-opening device. The device had maxillary and mandibular sections, was made of a thermoactive acrylic resin material, and was connected with 2 vertical screws in the right and left canine regions. The screws were adjusted daily to increase the oral opening, such that each turn of the screws increased the opening by 0.25 mm. With the help of this device, at the end of a 4-month follow-up period, the patient's maximal interdental distance had increased from 7.16 mm to 19.50 mm. The intraoral opening device described in this study is useful for achieving a vertical opening sufficient to perform dental treatment. PMID- 26548883 TI - Effect of an experimental silica-nylon reinforcement on the fracture load and flexural strength of bisacrylic interim partial fixed dental prostheses. AB - STATEMENT OF THE PROBLEM: Materials used in the fabrication of interim restorations usually have mechanical properties inferior to those used in definitive prostheses. Various techniques may be used to reinforce these materials. PURPOSE: The purpose of this in vitro study was to evaluate the fracture strength of interim partial fixed dental prostheses (FDPs) with and without an experimental silica-nylon reinforcement placed in different orientations (horizontal or vertical) before and after thermocycling and to evaluate the flexural strength of the bisacrylic resin used for fabricating these prostheses. MATERIAL AND METHODS: For fracture strength testing, 72 four-unit interim partial FDPs were fabricated from bisacrylic resin and divided into 3 groups: no reinforcement, horizontal reinforcement, and vertical reinforcement. Half of the specimens from each group were thermocycled before testing (1000 cycles between 5 degrees C and 55 degrees C) (n=12). An increasing load was applied to the center of the prosthesis until fracture. The flexural strength of bisacrylic resin reinforced with the experimental mesh was measured by using a 3 point bending test with 25*10.5*3.3 mm bars of resin, with or without thermocycling. The results were evaluated with analysis of variance and Kaplan Meier survival analysis (alpha=.05). RESULTS: The results showed that incorporating the experimental silica-nylon reinforcement in a horizontal orientation provided the highest values of fracture strength for the 4-unit partial FDPs. Reinforcement also enhanced the flexural strength values of bisacrylic resin bars. CONCLUSION: Silica-nylon reinforcement is an effective method of increasing the strength of interim restorations. PMID- 26548884 TI - Effect of different initial finishes and Parylene coating thickness on the surface properties of coated PMMA. AB - STATEMENT OF THE PROBLEM: The colonization of microorganisms on acrylic resin dentures may result in denture-induced stomatitis. No efficient coating has yet been proposed to address this issue. PURPOSE: The purpose of this in vitro study was to assess the effect of various initial surface finishes and different Parylene coating thicknesses on the surface roughness (Ra) and surface free energy (SFE) of Parylene coated polymethyl methacrylate (PMMA). MATERIAL AND METHODS: One hundred and sixty PMMA specimens were produced and divided into 8 groups as follows: group A: uncoated, 1000 grit finish; group Ap1: 10 MUm Parylene coated, 1000 grit finish; group B: uncoated, 1200 grit finish; group Bp: 10 MUm Parylene coated, 1200 grit finish; group C: uncoated, 2400 grit finish; group Cp: 10 MUm Parylene coated, 2400 grit finish; group Ap2: 20 MUm Parylene coated, 1000 grit finish; group Ap3: 30 MUm Parylene coated, 1000 grit finish. The Ra of all specimens was measured with a noncontact profilometer. To calculate the SFE, the Owens-Wendt approach was applied after measuring the contact angles with a goniometer. The topography of the specimens was observed by scanning electron microscope. RESULTS: Groups Ap1 and Bp presented significantly lower Ra values compared with their respective uncoated groups A and B (P<.001). No statistical difference was found between the Ra values of groups C and Cp, between A and Ap3, and between Ap2 and Ap3. The SFE values of the coated groups were significantly higher than the SFE values of the uncoated groups with the same initial finish (P<.001). CONCLUSIONS: Coating with a 10-MUm layer of Parylene C resulted in lower Ra values for the rougher groups and increased SFE values. Increasing the coating thickness resulted in an increase of the Ra. PMID- 26548885 TI - Effect of different dental ceramic systems on the wear of human enamel: An in vitro study. AB - STATEMENT OF PROBLEM: The wear of tooth structure opposing different advanced dental ceramic systems requires investigation. PURPOSE: The purpose of this in vitro study was to compare the wear of advanced ceramic systems against human enamel antagonists. MATERIAL AND METHODS: Four ceramic systems (IPS e.max Press, IPS e.max CAD, Noritake Super Porcelain EX-3, and LAVA Plus Zirconia) and 1 control group containing human enamel specimens were used in this study (n = 12). All specimens were fabricated as disks 11 mm in diameter and 3 mm thick. The mesiopalatal cusps of the maxillary third molars were prepared to serve as the enamel styluses. All specimens were embedded individually in 25 mm(3) autopolymerizing acrylic resin blocks. Wear was measured with a cyclic loading machine and a newly designed wear simulator. All enamel styluses (cusps) were scanned using the Activity 880 digital scanner (SmartOptics). Data from the base line and follow-up scans were collected and compared with Qualify 2012 3 dimensional (3D) and 2D digital inspection software (Geomagic), which aligned the models and detected the geometric changes and the wear caused by the antagonist specimen. One-way ANOVA was used to analyze the collected data. RESULTS: After 125,000 bidirectional loading cycles, the mean loss of opposing enamel volume for the enamel disks in the control group was 37.08 MUm(3), the lowest mean value for IPS e.max Press system was 39.75 MUm(3); 40.58 MUm(3) for IPS e.max CAD; 45.08 MUm(3) for Noritake Super Porcelain EX-3 system; and 48.66 MUm(3) for the Lava Plus Zirconia system. No statically significant differences were found among the groups in opposing enamel volume loss (P=.225) or opposing enamel height loss (P=.149). In terms of opposing enamel height loss, Lava Plus Zirconia system showed the lowest mean value of 27.5 MUm. The mean value for the IPS e.max CAD system was 27.91 MUm; 29.08 MUm for the control enamel; 33.25 MUm for the IPS e.max Press system; and 34.75 MUm for the Noritake Super Porcelain EX-3 system. CONCLUSIONS: Within the limitations of this in vitro study, no differences were found in the linear and volumetric reduction of enamel cusps abraded against enamel disks and all other ceramic specimens. All ceramic systems exhibited high durability and were wear-friendly to opposing enamel. PMID- 26548886 TI - Dentin translucency and color evaluation in human incisors, canines, and molars. AB - STATEMENT OF PROBLEM: For restorations with excellent esthetics, an understanding of the optical properties of human dentin is needed. Little information is available on the translucency and color parameters of dentin and its relationship to tooth type and position. PURPOSE: The purpose of this in vitro study was to investigate the translucency and CIELab color coordinates of human dentin in both anterior (incisors and canines) and posterior teeth (molars) by using spectrophotometric and spectroradiometric assessment methods. MATERIAL AND METHODS: Uniformly thick specimens (2 mm) of midcoronal human dentin were taken from 33 central and lateral incisors, 7 canines, and 33 molars (all maxillary teeth). The CIELab color coordinates were measured with a clinical spectrophotometer (Easyshade Compact) and a noncontact spectroradiometer (SpectraScan PR-704). The translucency parameter (TP) was calculated. Bland Altman plots and Wilcoxon signed rank tests for paired samples were used to assess the agreement of the 2 measurement techniques. The differences between anterior and posterior dentin specimens regarding color coordinates and the translucency parameter were analyzed using Mann-Whitney-Wilcoxon rank sum tests. RESULTS: Statistically significant differences between spectrophotometric and spectroradiometric measurements of the TP and CIELab color coordinates were found in both groups of dentin specimens (P<.05). TP values of molar dentin specimens were significantly higher than those of the anterior ones, regardless of the assessment method (P<.001). Dentin specimens of the anterior teeth exhibited higher L* values but lower a* and b* values on both black and white backgrounds compared with molar dentin specimens. CONCLUSIONS: The dentin of anterior teeth was found to be lighter but less translucent and less chromatic than in molars, regardless of the assessment method used. PMID- 26548887 TI - Effect of accelerated aging on the fracture toughness of zirconias. AB - STATEMENT OF PROBLEM: Low temperature degradation (LTD) of yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) is of concern. PURPOSE: The purpose of this in vitro study was to assess the effect of accelerated aging on the Vickers hardness and fracture toughness of a newly developed Y-TZP and 2 primary Y-TZPs. MATERIAL AND METHODS: Two primary 3 mol% Y-TZP, Lava (LA), Everest Zirconium Soft (EV), and a new 3 mol% Y-TZP, ZirTough (NZ) were assessed. Specimens (n=30 each brand) of 10 * 10 * 3 mm were hydrothermally treated for accelerated aging to examine LTD. Five conditions were used (n = 5 per condition) as follows: control group (no aging); 5 hours at 134 degrees C/0.2 MPa (5h-134 degrees C); 100 hours at 134 degrees C/0.2 MPa (100 h-134 degrees C); 5 hours at 180 degrees C/1.0 MPa (5 h-180 degrees C); and 20 hours at 180 degrees C/1.0 MPa (20 h-180 degrees C). Fracture toughness was measured by using the indentation fracture (IF) method under a loading of 294 N and calculated from the obtained measurements. To observe differences in particle composition and fracture patterns, mirror polished test specimens (n=5 each brand) were re-sintered at 1200 degrees C for 1 hour as a thermal etching process, and a Vickers indenter was pressed into the test specimens according to the IF method. Test piece surfaces and cracks were observed with scanning electron microscopy (SEM). One-way ANOVA and the post- hoc (Scheffe test were used to examine) interlevel significant differences (alpha=.05). RESULTS: The Vickers hardness and fracture toughness were as follows: 1319 HV and 7.36 MPa . m(1/2) for LA, and 1371 HV and 6.76 MPa . m(1/2) for EV in no aging; 1334 HV and 7.02 MPa . m(1/2) for LA, and 1346 HV and 6.07 MPa . m(1/2) for EV in 5h-134 degrees C. No significant differences were found between no aging and 5h-134 degrees C for LA and EV for Vickers hardness and fracture toughness. Measurements could not be made for LA and EV for 100 h-134 degrees C, 5h-180 degrees C, or 20 h-180 degrees C because of fractures in the surface layer. For NZ, Vickers hardness and fracture toughness were as follows: 1261 HV and 15.60 MPa . m(1/2) in no aging; 1217 HV and 14.98 MPa . m(1/2) in 5h 134 degrees C; 1231 HV and 15.13 MPa . m(1/2) in 100 h-134 degrees C; 1252 HV and 15.51 MPa . m(1/2) in 5h-180 degrees C; 1224 HV and 15.01 MPa . m(1/2) in 20 h 180 degrees C. No significant differences were shown in the Vickers hardness and fracture toughness. SEM observations after the thermal etching processing of NZ showed zirconia particles and scattered alumina particles. CONCLUSION: Measurements with LA and EV could only be made for no aging and 5h-134 degrees C, and no significant differences were found in Vickers hardness and fracture toughness. Measurements were made with NZ under all conditions and no significant differences were found in Vickers hardness and fracture toughness. PMID- 26548888 TI - Selecting maxillary anterior tooth width by measuring certain facial dimensions in the Kurdish population. AB - STATEMENT OF PROBLEM: One of the most difficult aspects of complete denture fabrication is selecting appropriately sized maxillary anterior teeth that will harmonize with the face. There are no generally accepted or naturally observed principles to guide dentists in this selection. PURPOSE: The purpose of this study was to determine whether a relationship exists between various facial measurements and the different single or combined mesiodistal widths of maxillary anterior teeth in a Kurdish population. MATERIAL AND METHODS: A total of 65 Kurdish dental students participated in this study. Two standardized digital photographs of the face (relaxed and smiling capture) were recorded. The interpupillary distance (IPD), inner canthal distance (ICD), interalar distance (IAD), and width of the 2 central incisors were determined by Image J software. The mesiodistal width and the combined straight-line width of the centrals, laterals, and canines were measured directly from the casts of the participants with digital calipers. A simple linear regression and the Pearson correlation coefficient were used to investigate the relationship between the particular facial measurement and the widths of the anterior teeth (alpha=.05). RESULTS: Significant correlations existed between the IPD and different tooth measurements; the highest was with the mean width of the canines (r=0.55). The proposed proportion between the IPD and the central incisor width was 6.93. The golden proportion of the ICD to the width of the central incisors and of the IAD to the straight-line width of the 6 anterior teeth could be used as a dependent parameter in Kurdish men. CONCLUSIONS: The IPD can be used to predict the width of anterior teeth in both sexes. In men, the width of the central incisors may be estimated from the ICD and the straight-line width of the 6 anterior teeth from the IAD. PMID- 26548889 TI - Correlation of pressure and displacement during gingival displacement: An in vitro study. AB - STATEMENT OF PROBLEM: Although numerous gingival displacement materials are available, information is limited regarding the pressures that can atraumatically produce sufficient gingival displacement for a successful impression. PURPOSE: The purpose of this in vitro study was to measure pressure and the resulting movement of artificial gingiva during simulated gingival displacement. MATERIAL AND METHODS: An idealized tooth model was made from acrylic resin and polyvinyl siloxane to simulate the free gingiva, sulcus, and attachment. The pressure and displacement achieved by 3 materials (Expasyl, Expasyl New, and KnitTrax Cord) were measured. A stereoscopic digital measuring microscope was used to quantify the space generated by the displacement material. A pressure gauge was used to measure the corresponding pressures. RESULTS: The injection of Expasyl resulted in a displacement distance of 1.31 mm, Expasyl New 1.07 mm, and KnitTrax Cord 0.85 mm, which are within acceptable clinical parameters. The correlation between pressure and gap showed that Expasyl and Expasyl New behaved similarly, while KnitTrax Cord was different. Expasyl, Expasyl New, and KnitTrax Cord all had maximum pressures that would be considered atraumatic to the epithelial attachment. CONCLUSIONS: An increase in pressure resulted in an increase in displacement for the 2 paste materials. However, contrary to expectation, displacement decreased as pressure increased for the cord material. PMID- 26548890 TI - In vivo precision of conventional and digital methods of obtaining complete-arch dental impressions. AB - STATEMENT OF PROBLEM: Digital impression systems have undergone significant development in recent years, but few studies have investigated the accuracy of the technique in vivo, particularly compared with conventional impression techniques. PURPOSE: The purpose of this in vivo study was to investigate the precision of conventional and digital methods for complete-arch impressions. MATERIAL AND METHODS: Complete-arch impressions were obtained using 5 conventional (polyether, POE; vinylsiloxanether, VSE; direct scannable vinylsiloxanether, VSES; digitized scannable vinylsiloxanether, VSES-D; and irreversible hydrocolloid, ALG) and 7 digital (CEREC Bluecam, CER; CEREC Omnicam, OC; Cadent iTero, ITE; Lava COS, LAV; Lava True Definition Scanner, T-Def; 3Shape Trios, TRI; and 3Shape Trios Color, TRC) techniques. Impressions were made 3 times each in 5 participants (N=15). The impressions were then compared within and between the test groups. The cast surfaces were measured point-to-point using the signed nearest neighbor method. Precision was calculated from the (90%-10%)/2 percentile value. RESULTS: The precision ranged from 12.3 MUm (VSE) to 167.2 MUm (ALG), with the highest precision in the VSE and VSES groups. The deviation pattern varied distinctly according to the impression method. Conventional impressions showed the highest accuracy across the complete dental arch in all groups, except for the ALG group. CONCLUSIONS: Conventional and digital impression methods differ significantly in the complete-arch accuracy. Digital impression systems had higher local deviations within the complete arch cast; however, they achieve equal and higher precision than some conventional impression materials. PMID- 26548891 TI - Association between serum vitamin D level and history of falls in elderly Japanese patients with rheumatoid arthritis. PMID- 26548892 TI - The Effects of Alcohol Dependence on the Quality of Life and Sex Life of Women. AB - BACKGROUND: Alcohol dependence is a multi-dimensional and chronic disorder which affects the physical, psychological, social, sexual health and thus the quality of life of the individual. OBJECTIVES: This research was designed in order to determine the effect of alcohol dependence on the quality of life and sexual life of women. METHODS: The research was a cross-sectional and comparative relation study, consisting of a case study group constituted of women who consulted Prof. Dr. Mazhar Osman Mental Health and Disorders Training and Research Hospital's Alcohol and Substance Research, Treatment, Education Center between July 2009 and July 2010 and who were diagnosed as alcohol addicted and a healthy group, constituted of women who consulted the Gynecology Clinic of the same hospital (alcohol dependent group = 71, healthy group = 183). The data were collected using 'World Health Organization Quality of Life Scale Brief Form' (WHOQOL-BREF TR), Female Sexual Function Index (FSFI), Beck Depression Inventory (BDI). Data were analyzed by percentage, mean, chi-square, student's t-test, and multivariate analysis by use of SPSS 13.0 program. RESULTS: It was determined that the alcohol dependent women presented lower WHOQOL-BREF-TR sub-dimensions and lower FSFI total scores and sub-dimensions but higher scores in BDI scale in comparison to the healthy group. CONCLUSIONS: The alcohol dependence negatively affects the quality of life and sexual life in women. PMID- 26548893 TI - Intersection of genetics and epigenetics in monozygotic twin genomes. AB - As a final function of various epigenetic mechanisms, chromatin regulation is a transcription control process that especially demonstrates active interaction with genetic elements. Thus, chromatin structure has become a principal focus in recent genomics researches that strive to characterize regulatory functions of DNA variants related to diseases or other traits. Although researchers have been focusing on DNA methylation when studying monozygotic (MZ) twins, a great model in epigenetics research, interactions between genetics and epigenetics in chromatin level are expected to be an imperative research trend in the future. In this review, we discuss how the genome, epigenome, and transcriptome of MZ twins can be studied in an integrative manner from this perspective. PMID- 26548894 TI - Association Between Stress-Related Sleep Reactivity and Metacognitive Beliefs About Sleep in Insomnia Disorder: Preliminary Results. AB - To evaluate the relation between stress-related sleep reactivity and metacognitive beliefs about sleep in subjects with insomnia disorder (93) and in a group of healthy controls (30) a set of variables, including Ford Insomnia Response to Stress Test (FIRST) and Metacognition Questionnaire-Insomnia (MCQ-I), have been used. Internal consistency of the Italian version of FIRST was studied. Univariate correlation, regression analysis, and principal component analysis were also performed. The Italian version of FIRST showed good internal consistency and discriminant validity. Sleep reactivity was higher in women (p < .05) and correlates positively in both genders with metacognitive beliefs about sleep (p < .01) in insomnia. In insomnia, metacognitive beliefs may play a key role in modulating sleep reactivity. Therapeutic strategies acting selectively on metacognition to reduce stress-related sleep reactivity in insomnia may be useful. PMID- 26548895 TI - No cross-sectional evidence for an increased relation of cognitive and sensory abilities in old age. AB - OBJECTIVES: A key question in gerontological research concerns whether good functioning can be maintained in some cognitive abilities in old age, even if deficits occur in other cognitive or sensory abilities. Our goals were to investigate relations of cognitive and sensory abilities in old age, whether these relations differed in size across old age, and whether this was affected by general cognitive ability (processing speed), educational level, and/or general health status. METHODS: Two thousand eight hundred and twelve older adults (aged 65-101, M = 77.9 years) from the Vivre-Leben-Vivere survey served as cross sectional sample for the present study. We administered psychometric tests on processing speed (the speed of cognitive processing), cognitive flexibility (the ability to alternate between cognitive operations), and verbal abilities (vocabulary). In addition, we interviewed individuals on their hearing, eyesight, educational level, and general health status. We regressed sizes of relations between abilities (calculated within each 1-year age tranche) on mean age within the corresponding age tranche, with the number of participants within the corresponding age tranche as case weights. RESULTS: We observed a decrease in relations between processing speed and cognitive flexibility in old age that was particularly pronounced in individuals with high educational level (r = -.41). In contrast, we did not find differences in relations between other cognitive and sensory abilities across old age, which held for different levels of general cognitive ability, education, and general health status. CONCLUSION: Present data do not support the view of a generally increased relation of cognitive and sensory abilities in old age. PMID- 26548896 TI - Trichosanthin reduces the viability of SU-DHL-2 cells via the activation of the extrinsic and intrinsic apoptotic pathways. AB - Previous studies have indicated that trichosanthin (TCS) exerts antitumor activity by inducing apoptosis in numerous tumor cell lines. However, the effects of TCS on lymphoma remain to be elucidated. The current study demonstrated that TCS inhibited the proliferation of thirteen lymphoma cell lines in a dose dependent manner, with SU-DHL-2 cells exhibiting the greatest sensitivity to TCS. Treatment of SU-DHL-2 cells with TCS led to cell cycle arrest at the S to G2/M phase transition. Furthermore, flow cytometric analysis, Hoechst 33258 staining and western blotting indicated that TCS induced the apoptosis of SU-DHL-2 cells in a time- and concentration-dependent manner. In addition, the activation of caspase-3 and -7 and poly (ADP-ribose) polymerase were observed. Pharmacological pan-caspase inhibition was observed to reduce TCS-induced apoptosis. Inhibition of caspase-8 or -9 alone was observed to partially reverse the effect of TCS on apoptosis. In conclusion, the current study indicates that TCS may induce apoptosis in SU-DHL-2 cells via the extrinsic and intrinsic pathways. PMID- 26548897 TI - Novel systemic therapies for the treatment of psoriasis. AB - INTRODUCTION: The immunopathogenesis of psoriasis has led to the discovery and development of several promising treatment options for psoriasis, including those that target the IL-17 and IL-23 pathways as well as small molecules that act on intracellular signaling pathways including the Janus kinase inhibitor and phosphodiesterase-4 inhibitor. Studies have demonstrated efficacy although long term risks are not fully known. This review looks at novel systemic therapies for psoriasis that have emerged recently. AREAS COVERED: Systemic treatments for psoriasis that are in the late phase of development were reviewed, with the main focus on the efficacy and adverse effects of individual treatments. EXPERT OPINION: The future of psoriasis treatment is likely to be based on clinical, genetic and immune biomarkers that will individualize treatment and may potentially optimize disease outcome. PMID- 26548898 TI - Topological, non-topological and instanton droplets driven by spin-transfer torque in materials with perpendicular magnetic anisotropy and Dzyaloshinskii Moriya Interaction. AB - The interfacial Dzyaloshinskii-Moriya Interaction can modify the topology of droplets excited by a localized spin-polarized current. Here, we show that, in addition to the stationary droplet excitations with skyrmion number either one (topological) or zero (non-topological), there exists, for a fixed current, an excited mode with a non-stationary time behavior. We call this mode "instanton droplet", which is characterized by time domain transitions of the skyrmion number. These transitions are coupled to an emission of incoherent spin-waves that can be observed in the frequency domain as a source of noise. Our results are interesting from a fundamental point of view to study spin-wave emissions due to a topological transition in current-driven systems, and could open the route for experiments based on magnetoresistance effect for the design of a further generation of nanoscale microwave oscillators. PMID- 26548899 TI - The association of socio-economic factors with physical fitness and activity behaviours, spinal posture and retinal vessel parameters in first graders in urban Switzerland. AB - Socio-economic status during childhood has been shown to be a strong predictor of adult health outcome. Therefore, we examined associations of parental educational level, household income and migrant background with physical fitness, spinal flexibility, spinal posture as well as retinal vessel diameters in children of an urban Swiss region. A total of 358 first graders of the Swiss canton Basel-Stadt (age: 7.3, SD: 0.4) were examined. Physical fitness (20 m shuttle run test, 20 m sprint, jumping sidewards and balancing backwards), spinal flexibility and spinal posture (MediMouse(r), Idiag, Fehraltdorf, Switzerland) and retinal microcirculation (Static Retinal Vessel Analyzer, Imedos Systems UG, Jena, Germany) were assessed. Parental education, household income, migrant background and activity behaviour were evaluated with a questionnaire. Parental education was associated with child aerobic fitness (P = 0.03) and screen time (P < 0.001). Household income was associated with jumping sidewards (P = 0.009), balancing backwards (P = 0.03) and sports club participation (P = 0.02). Migrant background was associated with BMI (P = 0.001), body fat (P = 0.03), aerobic fitness (P = 0.007), time spent playing outdoors (P < 0.001) and screen time (P < 0.001). For spinal flexibility and retinal vessel diameter, no associations were found (0.06 < P < 0.8). Low parental education, low household income and a migrant background are associated with poor physical fitness, higher BMI and body fat percentage and low-activity behaviour. PMID- 26548900 TI - Frequency-noise measurements of optical frequency combs by multiple fringe-side discriminator. AB - The frequency noise of an optical frequency comb is routinely measured through the hetherodyne beat of one comb tooth against a stable continuous-wave laser. After frequency-to-voltage conversion, the beatnote is sent to a spectrum analyzer to retrive the power spectral density of the frequency noise. Because narrow-linewidth continuous-wave lasers are available only at certain wavelengths, heterodyning the comb tooth can be challenging. We present a new technique for direct characterization of the frequency noise of an optical frequency comb, requiring no supplementary reference lasers and easily applicable in all spectral regions from the terahertz to the ultraviolet. The technique is based on the combination of a low finesse Fabry-Perot resonator and the so-called "fringe-side locking" method, usually adopted to characterize the spectral purity of single-frequency lasers, here generalized to optical frequency combs. The effectiveness of this technique is demonstrated with an Er-fiber comb source across the wavelength range from 1 to 2 MUm. PMID- 26548901 TI - Scalable Preparation of Ternary Hierarchical Silicon Oxide-Nickel-Graphite Composites for Lithium-Ion Batteries. AB - Silicon monoxide is a promising anode candidate because of its high theoretical capacity and good cycle performance. To solve the problems associated with this material, including large volume changes during charge-discharge processes, we report a ternary hierarchical silicon oxide-nickel-graphite composite prepared by a facile two-step ball-milling method. The composite consists of nano-Si dispersed silicon oxides embedded in nano-Ni/graphite matrices (Si@SiOx /Ni/graphite). In the composite, crystalline nano-Si particles are generated by the mechanochemical reduction of SiO by ball milling with Ni. These nano-Si dispersed oxides have abundant electrochemical activity and can provide high Li ion storage capacity. Furthermore, the milled nano-Ni/graphite matrices stick well to active materials and interconnect to form a crosslinked framework, which functions as an electrical highway and a mechanical backbone so that all silicon oxide particles become electrochemically active. Owing to these advanced structural and electrochemical characteristics, the composite enhances the utilization efficiency of SiO, accommodates its large volume expansion upon cycling, and has good ionic and electronic conductivity. The composite electrodes thus exhibit substantial improvements in electrochemical performance. This ternary hierarchical Si@SiOx /Ni/graphite composite is a promising candidate anode material for high-energy lithium-ion batteries. Additionally, the mechanochemical ball-milling method is low cost and easy to reproduce, indicating potential for the commercial production of the composite materials. PMID- 26548902 TI - EDITORIAL: Advances in Pharmacological Treatment of Cancer in Digestive Organs. PMID- 26548903 TI - Current Systemic Treatment and Emerging Therapeutic Strategies in Pancreatic Adenocarcinoma. AB - The purpose of this article is to provide a critical review of the current systemic treatment and the emerging targeted therapeutic strategies in pancreatic adenocarcinoma. Cytotoxic chemotherapeutic drugs have been used for palliative treatment of pancreatic adenocarcinoma, as well as for neoadjuvant therapy to facilitate surgical resection, and as adjuvant therapy to prevent tumor recurrence. The recent findings of early metastasis of cancer cells in pancreatic adenocarcinoma provide support for systemic therapy even in the case of small and localized tumors. However, the clinical benefits of systemic chemotherapy are generally limited and it is typically associated with a multitude of toxicities. Cancer-specific therapies with improved efficacy and safety are urgently needed. Tremendous advances have been made in understanding the biology and genetic regulation of normal and neoplastic development of the pancreas. These have led to identification of molecular targets in pancreatic cancer cells, the tumor microenvironment, and the cancer stem cells. Tumor-specific modalities are emergent by exploitation of the aberrant signaling pathways and molecular alterations in pancreatic cancer with the goals of improving treatment response. Integrative approaches that combine various targeting strategies with molecular bioinformatics will hopefully lead to the development of personalized therapies that may produce a positive impact on the quality of life and survival for patients with this deadly disease. PMID- 26548904 TI - Current and Emerging Systemic Therapy in Gastro-Esophageal Cancer "The Old and New Therapy for Metastatic Disease, The Role of Adjuvant and Neoadjuvant Therapy for Localized Disease". AB - Cancers of esophagus and stomach are common malignant diseases worldwide, and they are associated with serious morbidity and high mortality rates. When diagnosed at an early stage, gastro-esophageal cancers are potentially curable. Neo-adjuvant or adjuvant therapies using both chemotherapy and radiation therapy have been shown to reduce the risk of local recurrence and distant metastasis. For advanced or metastatic tumors, systemic chemotherapy offers symptomatic palliation and moderate benefits in survival. With recent advances in anti-cancer therapeutics, progress has been made to improve treatment response and life expectancy in patients with advanced gastro-esophageal cancers. Furthermore, the clinical use of molecularly targeted agents in combination with cytotoxic chemotherapeutics is being evaluated in a number of ongoing clinical trials. In this article, we review currently used standard systemic therapies including recently evolving targeted therapies for metastatic gastro-esophageal cancers, as well as the proven role and the regimens that are used as neoadjuvant and adjuvant treatment in localized gastro-esophageal cancers. PMID- 26548905 TI - Novel and Emerging Targeted Therapies of Colorectal Cancer. AB - The survival rate of patients with colorectal cancer (CRC) is steadily increasing over the past decade. However, CRC continue to be one of the leading causes of cancer-related fatality in the United States. Current targeted strategies offer limited clinical benefits and the overall survival rate for CRC remains low. Improved understanding of the molecular changes associated with CRC that control growth factor signaling and evasion of cell death allow for the development of improved targeted therapy. This review aims to discuss some of the emerging therapies aimed to target CRC. PMID- 26548906 TI - Advances in the Pharmacologic Treatment of Hepatocellular Carcinoma. AB - Medical therapy for hepatocellular carcinoma (HCC) is an area of active investigation because fewer than 25% of patients are candidates for curative resection or transplantation. Single agent doxorubicin, the former standard of care, generated a 10% tumor response but resulted in substantial toxicity. The resulting recommendation of the NCCN has been to administer cytotoxic chemotherapy only under clinical protocol. More recently, newer drugs with more specific targets have forced re-consideration of palliative chemotherapy in clinical practice. Bevacizumab is a promising therapy but data is limited to Phase 2 trials without impressive results. Sorafenib is the prototype multi kinase inhibitor, which has demonstrated some but limited survival benefit in advanced HCC. This has subsequently become the standard of care. Epidermal growth factor receptor, the target of rapamycin (mTOR) pathway, transforming growth factor-beta, and cyclin-dependent kinases have been recent targets of ongoing study for potential therapeutics. Overall, current therapeutics have been so promising that adjuvant therapy after curative treatment in under investigation to reduce recurrence. PMID- 26548907 TI - Advances in Systemic Therapy for Gastroenteropancreatic Neuroendocrine Malignancies. AB - Neuroendocrine tumors (NETs) are relatively uncommon. They typically arise in the gastrointestinal tract and lungs, and their incidence seems to be rising. Most patients have advanced disease at the time of diagnosis and many more will relapse after surgery. There is thus a great need for improvements in therapy for advanced neuroendocrine tumors. This article reviews the current therapy for both pancreatic NETs and non-pancreatic gastrointestinal NETs, and discusses recent advances in NET management with an emphasis on targeted therapy. PMID- 26548908 TI - Imatinib Dosing in Gastrointestinal Stromal Tumors (GISTs): When, How Much, and How Long? AB - Imatinib therapy has revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Compared with older therapy, imatinib significantly improves outcomes in patients with metastatic disease and those with locally advanced tumors, raising progression-free and overall survival. Recent studies have evaluated variables such as timing of treatment, total dosing, and duration of therapy. Different genotypes are associated with a poorer response to imatinib therapy, whereas others may benefit from a higher starting dose. This review discusses recent data regarding optimal use of imatinib for treatment of GIST in both the adjuvant and metastatic settings, and addresses topics such as the impact of genotype on initial dose, dose escalation, optimal duration of treatment, and neoadjuvant therapy. Key ongoing clinical trials of imatinib in GIST are also discussed. PMID- 26548910 TI - The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs. AB - The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature. PMID- 26548911 TI - It's diversity all the way down. AB - This month's Genome Watch highlights how single-cell transcriptomic analysis of infected macrophages has provided insight into the diversity in host-pathogen interactions. PMID- 26548909 TI - Mitochondria-related miR-141-3p contributes to mitochondrial dysfunction in HFD induced obesity by inhibiting PTEN. AB - Mitochondria-related microRNAs (miRNAs) have recently emerged as key regulators of cell metabolism and can modulate mitochondrial fusion and division. In order to investigate the roles of mitochondria-related miRNAs played in obesity, we conducted comprehensive molecular analysis in vitro and in vivo. Based on high fat-diet (HFD) induced obese mice, we found that hepatic mitochondrial function was markedly altered. Subsequently, we evaluated the expression levels of selected mitochondria-related miRNAs and found that miR-141-3p was up-regulated strikingly in HFD mice. To further verify the role of miR-141-3p in obesity, we carried out gain-and-loss-of-function study in human HepG2 cells. We found that miR-141-3p could modulate ATP production and induce oxidative stress. Through luciferase report gene assay, we identified that phosphatase and tensin homolog (PTEN) was a target of miR-141-3p. Inhibiting PTEN could alter the mitochondrial function, too. Our study suggested that mitochondria-related miR-141-3p induced mitochondrial dysfunction by inhibiting PTEN. PMID- 26548912 TI - Parasite biology: A perfectly timed escape. PMID- 26548913 TI - A century of the phage: past, present and future. AB - Viruses that infect bacteria (bacteriophages; also known as phages) were discovered 100 years ago. Since then, phage research has transformed fundamental and translational biosciences. For example, phages were crucial in establishing the central dogma of molecular biology - information is sequentially passed from DNA to RNA to proteins - and they have been shown to have major roles in ecosystems, and help drive bacterial evolution and virulence. Furthermore, phage research has provided many techniques and reagents that underpin modern biology - from sequencing and genome engineering to the recent discovery and exploitation of CRISPR-Cas phage resistance systems. In this Timeline, we discuss a century of phage research and its impact on basic and applied biology. PMID- 26548916 TI - Biofilms: Electrifying long-range signalling. PMID- 26548915 TI - Modulation of p53 during bacterial infections. AB - In recent years, numerous bacterial pathogens have been shown to inactivate the major tumour suppressor p53 during infection. This inactivation impedes the protective response of the host cell to the genotoxicity that often results from bacterial infection. Moreover, a new aspect of the antibacterial activity of p53 that has recently come to light - downregulation of host cell metabolism to interfere with intracellular bacterial replication - has further highlighted the crucial role of p53 in host-pathogen interactions, as host cell metabolism is relevant for all intracellular bacteria, as well as other pathogens that replicate inside host cells and use host metabolites. In this Progress article, we summarize recent work that has advanced our knowledge of the interaction between pathogenic bacteria and p53, and we discuss the known and expected outcomes of this interaction for pathogenesis. PMID- 26548917 TI - Structural biology: How CRISPR captures spacer invaders. PMID- 26548914 TI - Twenty years of bacterial genome sequencing. AB - Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond. PMID- 26548918 TI - Homogeneous and heterogeneous degradation of caffeic acid using photocatalysis driven by UVA and solar light. AB - Waste water from the wine industry is characterized by a high concentration of dissolved organic matter and the presence of natural phenolic compounds with low biodegradability. High concentrations of phenolic compounds may cause environmental pollution and risks to human health. In this article caffeic acid (CA) was used as a model compound of wine effluent because it is refractory to the conventional wastewater treatments. The oxidation of caffeic acid in water solution (0.01 g L(-1)) by heterogeneous photocatalysis and photo-Fenton reaction was studied using UVA. The optimal conditions for each treatment were performed by multivariate experimental design. The optimal conditions for heterogeneous photocatalysis were pH 5.3 and 0.9 g L(-1) TiO2. In the case of photo-Fenton treatment, optimized variable were 82.4 MUmol L(-1) of Fe(2+) and 558.6 MUmol L( 1) of H2O2. The degradation profiles of CA were monitored by UV-Vis, HPLC, TOC and COD. To reach 90% of CA removal, 40 and 2 min of reaction, respectively, were required by heterogeneous and photo-Fenton processes, respectively. For comparison purposes, the reactions were also performed under solar light. The use of solar light does not change the efficiency of the photo-Fenton reaction, yet the performance of the heterogeneous process was significantly improved, reaching 90% of degradation in 15 min. PMID- 26548919 TI - Genetic causes of MCPH in consanguineous Pakistani families. PMID- 26548920 TI - Allergic contact dermatitis induced by the anionic surfactant, sodium N-methyl-N (1-oxododecyl)-beta-alaninate, contained in a daily-use shampoo. PMID- 26548922 TI - Is competition needed for ecological character displacement? Does displacement decrease competition? AB - Interspecific competition for resources is generally considered to be the selective force driving ecological character displacement, and displacement is assumed to reduce competition. Skeptics of the prevalence of character displacement often cite lack of evidence of competition. The present article uses a simple model to examine whether competition is needed for character displacement and whether displacement reduces competition. It treats systems with competing resources, and considers cases when only one consumer evolves. It quantifies competition using several different measures. The analysis shows that selection for divergence of consumers occurs regardless of the level of between resource competition or whether the indirect interaction between the consumers is competition (-,-), mutualism (+,+), or contramensalism (+,-). Also, divergent evolution always decreases the equilibrium population size of the evolving consumer. Whether divergence of one consumer reduces or increases the impact of a subsequent perturbation of the other consumer depends on the parameters and the method chosen for measuring competition. Divergence in mutualistic interactions may reduce beneficial effects of subsequent increases in the other consumer's population. The evolutionary response is driven by an increase in the relative abundance of the resource the consumer catches more rapidly. Such an increase can occur under several types of interaction. PMID- 26548921 TI - Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop. AB - Plasminogen activator inhibitor-1 (PAI-1) is a biologically important serine protease inhibitor (serpin) that, when overexpressed, is associated with a high risk for cardiovascular disease and cancer metastasis. Several of its ligands, including vitronectin, tissue-type and urokinase-type plasminogen activator (tPA, uPA), affect the fate of PAI-1. Here, we measured changes in the solvent accessibility and dynamics of an important unresolved functional region, the reactive center loop (RCL), upon binding of these ligands. Binding of the catalytically inactive S195A variant of tPA to the RCL causes an increase in fluorescence, indicating greater solvent protection, at its C-terminus, while mobility along the loop remains relatively unchanged. In contrast, a fluorescence increase and large decrease in mobility at the N-terminal RCL is observed upon binding of S195A-uPA to PAI-1. At a site distant from the RCL, binding of vitronectin results in a modest decrease in fluorescence at its proximal end without restricting overall loop dynamics. These results provide the new evidence for ligand effects on RCL conformation and dynamics and differences in the Michaelis complex with plasminogen activators that can be used for the development of more specific inhibitors to PAI-1. This study is also the first to use electron paramagnetic resonance (EPR) spectroscopy to investigate PAI-1 dynamics. SIGNIFICANCE: Balanced blood homeostasis and controlled cell migration requires coordination between serine proteases, serpins, and cofactors. These ligands form noncovalent complexes, which influence the outcome of protease inhibition and associated physiological processes. This study reveals differences in binding via changes in solvent accessibility and dynamics within these complexes that can be exploited to develop more specific drugs in the treatment of diseases associated with unbalanced serpin activity. PMID- 26548923 TI - Long non-coding RNA-GAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (C-C motif) ligand 1 expression. AB - Long non-coding RNAs (lncRNAs) have important roles in diverse biological processes, including transcriptional regulation, cell growth and tumorigenesis. The present study aimed to investigate whether lncRNA-growth arrest-specific (GAS)5 regulated bladder cancer progression via regulation of chemokine (C-C) ligand (CCL)1 expression. The viability of BLX bladder cancer cells was detected using a Cell Counting kit-8 assay, and cell apoptosis was assessed by annexin V propidium iodide double-staining. The expression levels of specific genes and proteins were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. In addition, cells were transfected with small interfering (si)RNAs or recombinant GAS5 in order to silence or overexpress GAS5, respectively. The results of the present study demonstrated that knockdown of GAS5 expression promoted bladder cancer cell proliferation, whereas overexpression of GAS5 suppressed cell proliferation. Furthermore, knockdown of GAS5 resulted in an increased percentage of cells in S and G2 phase, and a decreased percentage of cells in G1 phase. In addition, the present study performed a hierarchical cluster analysis of differentially expressed lncRNAs in bladder cancer cells and detected that CCL1 overexpression resulted in an upregulation of GAS5, which may improve the ability of cells to regulate a stress response in vitro. Furthermore, knockdown of GAS5 expression increased the mRNA and protein expression of CCL1 in bladder cancer cells. Gain-of-function and loss of-function studies demonstrated that GAS5 was able to inhibit bladder cancer cell proliferation, at least in part, by suppressing the expression of CCL1. The results of the present study demonstrated that GAS5 was able to suppress bladder cancer cell proliferation, at least partially, by suppressing the expression of CCL1. The results of the present study may provide a basis for developing novel effective treatment strategies against bladder cancer. PMID- 26548924 TI - An oncolytic parasite to treat polycythemia vera. PMID- 26548925 TI - SENP1 desensitizes hypoxic ovarian cancer cells to cisplatin by up-regulating HIF 1alpha. AB - Hypoxia-inducible factor 1 alpha (HIF-1alpha) is closely related to chemoresistance of ovarian cancers. Although it is reported that HIF-1alpha can be regulated by Sentrin/SUMO-specific protease 1 (SENP1), the effects of SENP1 on HIF-1alpha is still controversial. In this study, we identified that SENP1 positively regulated the expression of HIF-1alpha by deSUMOylation and weakened the sensitivity of hypoxic ovarian cancer cells to cisplatin. These results indicate that SENP1 is a positive regulator of HIF-1alpha and plays a negative role in ovarian cancer chemotherapy. PMID- 26548926 TI - Molecular Engineering of Pyrido[3,4-b]pyrazine-Based Donor-Acceptor-pi-Acceptor Organic Sensitizers: Effect of Auxiliary Acceptor in Cobalt- and Iodine-Based Electrolytes. AB - Due to the ease of tuning its redox potential, the cobalt-based redox couple has been extensively applied for highly efficient dye-sensitized solar cells (DSSCs) with extraordinarily high photovoltages. However, a cobalt electrolyte needs particular structural changes in the organic dye components to obtain such high photovoltages. To achieve high device performance, specific requirements in the molecular tailoring of organic sensitizers still need to be met. Besides the need for large electron donors, studies of the auxiliary acceptor segment of donor acceptor-pi-acceptor (D-A-pi-A) organic sensitizers are still rare in molecular optimization in the context of cobalt electrolytes. In this work, two novel organic D-A-pi-A-type sensitizers (IQ13 and IQ17) have been developed and exploited in cobalt- and iodine-based redox electrolyte DSSCs, specifically to provide insight into the effect of pi-bridge modification in different electrolytes. The investigation has been focused on the additional electron withdrawing acceptor capability with grafted long alkoxy chains. Optoelectronic transient measurements have indicated that IQ17 containing a pyrido[3,4 b]pyrazine moiety bearing long alkoxyphenyl chains is more suitable for application in cobalt-based DSSCs. PMID- 26548927 TI - Response to Comment on New Mathematical Model for Interpreting pH-Stat Digestion Profiles: Impact of Lipid Droplet Characteristics on in Vitro Digestibility. PMID- 26548928 TI - Elucidation of the resting state of a rhodium NNN-pincer hydrogenation catalyst that features a remarkably upfield hydride (1)H NMR chemical shift. AB - Rhodium(I) alkene complexes of an NNN-pincer ligand catalyze the hydrogenation of alkenes, including ethylene. The terminal or resting state of the catalyst, which exhibits an unprecedentedly upfield Rh-hydride (1)H NMR chemical shift, has been isolated and a synthetic cycle for regenerating the catalytically active species has been established. PMID- 26548929 TI - Why solid oxide cells can be reversibly operated in solid oxide electrolysis cell and fuel cell modes? AB - High temperature solid oxide cells (SOCs) are attractive for storage and regeneration of renewable energy by operating reversibly in solid oxide electrolysis cell (SOEC) and solid oxide fuel cell (SOFC) modes. However, the stability of SOCs, particularly the deterioration of the performance of oxygen electrodes in the SOEC operation mode, is the most critical issue in the development of high performance and durable SOCs. In this study, we investigate in detail the electrochemical activity and stability of La0.8Sr0.2MnO3 (LSM) oxygen electrodes in cyclic SOEC and SOFC modes. The results show that the deterioration of LSM oxygen electrodes caused by anodic polarization can be partially or completely recovered by subsequent cathodic polarization. Using in situ assembled LSM electrodes without pre-sintering, we demonstrate that the deteriorated LSM/YSZ interface can be repaired and regenerated by operating the cells under cathodic polarization conditions. This study for the first time establishes the foundation for the development of truly reversible and stable SOCs for hydrogen fuel production and electricity generation in cyclic SOEC and SOFC operation modes. PMID- 26548930 TI - Mitochondria-targeted drug delivery system for cancer treatment. AB - Mitochondria are one type of the major organelles in the cell, participating in a variety of important physiological and biochemical processes, such as tricarboxylic acid cycle, fatty acid metabolism and oxidative phosphorylation. Meanwhile, it also happens to be the key regulator of apoptosis by triggering the complex cell-death processes through a variety of mechanisms. Since it plays a pivotal role in cell-death, a mitochondria-targeted treatment strategy could be promising for cancer therapy. In this comprehensive review, we focused on the mechanisms of mitochondrial targeting and a variety of strategies to realize the purpose of mitochondrial targeting, including that based on the use of lipophilic cations, and mitochondrial targeting signal peptides (MTS) as well as cell penetrating peptides (CPPs). Then on this basis we present some several developed strategies for multifunctional mitochondria-targeted agents so as to achieve the good anti-cancer therapeutic effects. PMID- 26548931 TI - Roles of Hippo signaling in lung cancer. AB - Lung cancer is the leading cause of cancer-related mortality in the world, with more than 1 million deaths/year. Over the past years, lung cancer treatment has been based on cytotoxic agents and an improvement in the outcome and quality of life for patients has been observed. However, it has become clear that additional therapeutic strategies are urgently required to provide an improved survival benefit for patients. A major intracellular signaling pathway, the Hippo signaling pathways have been extensively studied in neoplasia, including lung cancer. Furthermore, the study of constitutively activated receptor and their downstream signaling mediators has become a promising new field of investigation for lung cancer treatment. Nevertheless for lung cancer, this approach has not been successful yet. Here, we will review the molecular basis of Hippo signaling in lung cancer and further discuss the therapeutic potential of multi-targeted strategies involving Yes-associated protein inhibitors. PMID- 26548932 TI - A meta-analysis of erlotinib versus docetaxel for advanced nonsmall-cell lung cancer with poor prognosis. AB - BACKGROUND: The extent of the benefit of erlotinib in the treatment of advanced nonsmall-cell lung cancer (NSCLC) is still controversial when compared with docetaxel. This meta-analysis was performed to compare the efficacy of erlotinib with docetaxel for different patients with advanced NSCLC. MATERIALS AND METHODS: We searched Cochrane Library, PubMed, CNKI, and identified 23 randomized controlled clinical trials from 2008 to 2015. According to our further full-text screening, 6 clinical trials were included in the final meta-analysis. RESULTS: Six papers were included in this study. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were included in our outcomes. The pooled hazard ratio (HR) of PFS was 1.57 (95% confidential index [CI] = 1.47-1.69). The pooled HR of OS was 1.66 (95% CI = 1.43-1.92). The pooled risk ratio of ORR was 0.56 (95% CI = 0.35-0.91). The toxicity analysis showed odds ratio = 1.79 (95% CI = 1.20-2.69). CONCLUSIONS: In terms of PFS, OS, and toxicity the effect of erlotinib in the treatment of advanced NSCLC patients is superior to docetaxel. PMID- 26548933 TI - Rabbit nucleus pulposus cells facilitate differentiation of adipose-derived stem cells into nucleus pulposus-like cells. AB - OBJECTIVE: To investigate the feasibility of inducing adipose-derived stem cells (ADSCs) to nucleus pulposus cells (NPCs). MATERIALS AND METHODS: ADSCs were isolated from rabbit while NPCs were isolated from an allogeneic rabbit. NPCs were co-cultured with the 3rd generation ADSCs in co-cultured system. Only NPCs were cultured in single culturing group. Through the collagen type II collagen immunohistochemistry, we observed NPCs and then identify NPC. Proteoglycan messenger RNA (mRNA) and collagen type II mRNA level were measured by real-time polymerase chain reaction. RESULTS: In two group cells, collagen type II collagen were detected by immunohistochemistry. The amount of proteoglycan mRNA and collagen type II mRNA was both significantly higher in co-cultured group than in single cultured group. CONCLUSIONS: In some condition, ADSCs have the potency to differentiate toward nucleus pulposus-like cells. ADSCs are better seed cells for tissue engineering of artificial nucleus pulposus. PMID- 26548934 TI - Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. PATIENTS AND METHODS: Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. RESULTS: All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6 month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. CONCLUSION: Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases. PMID- 26548935 TI - Methylene tetrahydrofolate reductasel reductase C677T polymorphisms and esophageal cancer susceptibility: A meta-analysis based on Chinese Han population. AB - OBJECTIVE: The aim of this meta-analysis was to assess the methylene tetrahydrofolate reductase (MTHFR) gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. MATERIALS AND METHODS: The databases of PubMed, MEDLINE, Wanfang, and CNIK was electronic searched to find the case control or cohort study about the relationship between MTHFR gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. The odds ratio (OR) was used to assess the relationship between CC, CT, and TT genotype and esophageal cancer risk. The data were pooled using Stata 11.0 software. RESULTS: Eight articles included 1752 esophageal cancer and 2363 controls were found and included in this meta-analysis. The pooled OR was 1.86 with its 95% confidence interval of 1.21-2.86 and 1.62 with its 95% confidence interval of 1.15-2.27 for TT versus CC and CT versus CC model which indicated that people with TT OR CT genotype significant increase the risk of developing esophageal cancer. CONCLUSION: Esophageal cancer risk was significantly increased in people with TT/CT genotype of MTHFR gene. PMID- 26548936 TI - A meta-analysis of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer. AB - OBJECTIVE: To systematic review and analysis the clinical efficacy and toxicity of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: The databases of PubMed and CNKI were electronic searched with the free text word of lung cancer/NSCLC and lentinan. The prospective clinical study reporting the clinical efficacy and safety of lentinan injection combined with chemotherapy in the treatment of NSCLC were reviewed and included in this meta-analysis. The combined treatment efficacy and toxicity of lentinan injection combined with chemotherapy were pooled by Stata 11.0 software. RESULTS: Twelve clinical studies of lentinan injection combined with chemotherapy in the treatment of NSCLC with 458 controls and 492 NSCLCs patients were finally included in this meta-analysis. The pooled results indicated that the objective response rate was significant improved in the lentinan injection combined chemotherapy group compared with chemotherapy group only (relative risk [RR] = 1.31, 95% confidence interval [CI]: 1.14-1.52). The chemotherapy-related toxicity of III/IV gastrointestinal reaction (RR = 0.54, 95% CI: 0.43-0.68) and III/IV granulocytopenia (RR = 0.65, 95% CI: 0.51-0.70) were significant decreased in the combined group. CONCLUSION: Lentinan injection combined chemotherapy significant increase the objective response rate and decreased the chemotherapy-related toxicity. PMID- 26548937 TI - Toxicity and adverse effects of everolimus in the treatment of advanced nonsmall cell lung cancer pretreated with chemotherapy--Chinese experiences. AB - BACKGROUND: There is not more treatment selection for advanced nonsmall-cell lung cancer (NSCLC) patients who had disease progression after two previous treatments. Everolimus is an oral inhibitor of the mammalian target of rapamycin pathway, which is aberrantly activated in NSCLC. PATIENTS AND METHODS: Stage IV NSCLC patients, with one or multiple prior chemotherapy regimens, received everolimus 5-10 mg/day with or without chemotherapy until progression or unacceptable toxicity. The primary objective were toxicity of everolimus and overall disease control rate (DCR). RESULTS: 22 patients were enrolled. Common >= grade 3 events were stomatitis, dyspnea, vomiting, thrombocytopenia. Overall disease control rate was 54.5% among 22 patients, 1 had a partial response, and 11 had disease stabilization. Common >= Grade 3 events were stomatitis, dyspnea, vomiting, and thrombocytopenia. CONCLUSION: Everolimus was well tolerated, showing the modest clinical activity in heavily pretreated advanced NSCLC. PMID- 26548938 TI - Synchronous primary pulmonary lymphoma presenting with pulmonary adenocarcinoma: A case report and literature review. AB - The incidence of synchronous lung tumors is rare, as reported in various clinical series, ranging from 0.2% to 8%. Most reported cases of synchronous tumors were shown to have the same histologic types of lung cancer. Among possible combinations, squamous cell carcinoma was by far the most common. Primary pulmonary lymphoma (PPL) is very rare in clinics accounting for only 0.5-1% of primary lung tumors. There is no report about synchronous primary pulmonary adenocarcinoma presenting with lung lymphoma. It can be easily misdiagnosed or missed. Although the treatment of PPL and synchronous pulmonary tumors has controversial, surgery with/without postoperative adjuvant radio-chemotherapy are used for most patients in present. We describe a case of synchronous primary lung tumors presenting with lymphoma and adenocarcinoma, in which expression of the cell surface antigens were evaluated immunohistochemically. By taking into consideration of the reported experiences, the author discusses the clinical features, prognostic criteria and therapeutic management of synchronous lung cancer and PPL. PMID- 26548939 TI - A new perspective on the IIIC staging in Chinese patients with primary breast cancer: Single-center experiences. AB - PURPOSE: The purpose of this retrospective study was to investigate whether Stage IIIC (TanyN3M0) breast cancer can be classified further into subgroups with different prognosis. MATERIALS AND METHODS: One hundred and thirty-two patients with Stage IIIC breast cancer at Tianjin Medical University Cancer Institute and Hospital were analyzed. The disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method for lymph node ratio (LNR) and the number of positive lymph node (PLN). The receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of the LNR and PLN. The univariate and multivariate analysis were applied to identify the prognostic factors. RESULTS: The results showed that the optimal cut-off value of LNR value was 0.65, and the optimal cut-off value of PLN was 15. The Kaplan-Meier survival analysis showed the higher value of LNR or PLN was correlated with shortened DFS (P = 0.002, P = 0.008, respectively) and OS (P < 0.001, P = 0.001, respectively). In multivariate survival analysis, the value of LNR and PLN were still remained as independent prognostic factors for DFS (P = 0.014, P = 0.013, respectively) and OS (P = 0.004, P = 0.002, respectively). CONCLUSION: These results suggest that the value of LNR or PLN could be used as a new significant prognostic biomarker for Stage IIIC breast cancer patients. Stage IIIC breast cancer patients with lower value of LNR or PLN may be down staged. PMID- 26548940 TI - Predictors and rate of adjuvant radiation therapy following radical prostatectomy: A report from the Prostate Cancer Registry. AB - INTRODUCTION: Long-term data from three randomized trials have demonstrated that adjuvant radiation therapy (ART) reduces the rate of biochemical failure in high risk men following radical prostatectomy (RP). One of these trials has shown a survival advantage. We investigated the rate of ART in Victoria and the predictors for this treatment. METHODS: We analysed data from eligible patients who were notified to the Victorian Prostate Cancer Registry (PCR) by 37 Victorian hospitals between 1 August 2008 and 31 October 2011. We defined ART as radiation therapy (RT) delivered within 6 months of RP. Predictors of ART receipt were modelled using adjusted and unadjusted logistic regression. RESULTS: There were 4626 eligible cases from which 2018 underwent RP with recorded date of surgery. Of these eligible prostatectomy cases, a total of 89 received ART. A subgroup of 833 men had an adverse pathologic feature, of whom 78 received ART. In a multivariate model, pathologic tumour stage pT3a (odds ratio (OR) 2.64; 95% confidence interval (CI) 1.4-5.00; P = 0.003), pT3b (OR 4.58; 95% CI 2.12-9.89; P = 0.000), a positive surgical margin (OR 8.91; 95% CI 4.61-17.2; P = 0.000) and pathologic Gleason grade >7 (OR 7.18; 95% CI 1.54-33.6; P = 0.012) predicted receipt of ART. CONCLUSION: Adverse pathologic features and high pathologic Gleason score predict for receiving ART in Victorian men after RP, but overall, ART is not commonly prescribed. This finding is consistent with other published series and may reflect clinician scepticism regarding the benefit of ART over salvage RT and concern about toxicity and the risk of over treatment. PMID- 26548941 TI - Planar-integrated single-crystalline perovskite photodetectors. AB - Hybrid perovskites are promising semiconductors for optoelectronic applications. However, they suffer from morphological disorder that limits their optoelectronic properties and, ultimately, device performance. Recently, perovskite single crystals have been shown to overcome this problem and exhibit impressive improvements: low trap density, low intrinsic carrier concentration, high mobility, and long diffusion length that outperform perovskite-based thin films. These characteristics make the material ideal for realizing photodetection that is simultaneously fast and sensitive; unfortunately, these macroscopic single crystals cannot be grown on a planar substrate, curtailing their potential for optoelectronic integration. Here we produce large-area planar-integrated films made up of large perovskite single crystals. These crystalline films exhibit mobility and diffusion length comparable with those of single crystals. Using this technique, we produced a high-performance light detector showing high gain (above 10(4) electrons per photon) and high gain-bandwidth product (above 10(8) Hz) relative to other perovskite-based optical sensors. PMID- 26548942 TI - Ultrafast static and diffusion-controlled electron transfer at Ag29 nanocluster/molecular acceptor interfaces. AB - Efficient absorption of visible light and a long-lived excited state lifetime of silver nanoclusters (Ag29 NCs) are integral properties for these new clusters to serve as light-harvesting materials. Upon optical excitation, electron injection at Ag29 NC/methyl viologen (MV(2+)) interfaces is very efficient and ultrafast. Interestingly, our femto- and nanosecond time-resolved results demonstrate clearly that both dynamic and static electron transfer mechanisms are involved in photoluminescence quenching of Ag29 NCs. PMID- 26548943 TI - Multimodal emotional state recognition using sequence-dependent deep hierarchical features. AB - Emotional state recognition has become an important topic for human-robot interaction in the past years. By determining emotion expressions, robots can identify important variables of human behavior and use these to communicate in a more human-like fashion and thereby extend the interaction possibilities. Human emotions are multimodal and spontaneous, which makes them hard to be recognized by robots. Each modality has its own restrictions and constraints which, together with the non-structured behavior of spontaneous expressions, create several difficulties for the approaches present in the literature, which are based on several explicit feature extraction techniques and manual modality fusion. Our model uses a hierarchical feature representation to deal with spontaneous emotions, and learns how to integrate multiple modalities for non-verbal emotion recognition, making it suitable to be used in an HRI scenario. Our experiments show that a significant improvement of recognition accuracy is achieved when we use hierarchical features and multimodal information, and our model improves the accuracy of state-of-the-art approaches from 82.5% reported in the literature to 91.3% for a benchmark dataset on spontaneous emotion expressions. PMID- 26548944 TI - Goal-oriented robot navigation learning using a multi-scale space representation. AB - There has been extensive research in recent years on the multi-scale nature of hippocampal place cells and entorhinal grid cells encoding which led to many speculations on their role in spatial cognition. In this paper we focus on the multi-scale nature of place cells and how they contribute to faster learning during goal-oriented navigation when compared to a spatial cognition system composed of single scale place cells. The task consists of a circular arena with a fixed goal location, in which a robot is trained to find the shortest path to the goal after a number of learning trials. Synaptic connections are modified using a reinforcement learning paradigm adapted to the place cells multi-scale architecture. The model is evaluated in both simulation and physical robots. We find that larger scale and combined multi-scale representations favor goal oriented navigation task learning. PMID- 26548945 TI - Off-line simulation inspires insight: A neurodynamics approach to efficient robot task learning. AB - There is currently an increasing demand for robots able to acquire the sequential organization of tasks from social learning interactions with ordinary people. Interactive learning-by-demonstration and communication is a promising research topic in current robotics research. However, the efficient acquisition of generalized task representations that allow the robot to adapt to different users and contexts is a major challenge. In this paper, we present a dynamic neural field (DNF) model that is inspired by the hypothesis that the nervous system uses the off-line re-activation of initial memory traces to incrementally incorporate new information into structured knowledge. To achieve this, the model combines fast activation-based learning to robustly represent sequential information from single task demonstrations with slower, weight-based learning during internal simulations to establish longer-term associations between neural populations representing individual subtasks. The efficiency of the learning process is tested in an assembly paradigm in which the humanoid robot ARoS learns to construct a toy vehicle from its parts. User demonstrations with different serial orders together with the correction of initial prediction errors allow the robot to acquire generalized task knowledge about possible serial orders and the longer term dependencies between subgoals in very few social learning interactions. This success is shown in a joint action scenario in which ARoS uses the newly acquired assembly plan to construct the toy together with a human partner. PMID- 26548946 TI - Olfaction and topography, but not magnetic cues, control navigation in a pelagic seabird: displacements with shearwaters in the Mediterranean Sea. AB - Pelagic seabirds wander the open oceans then return accurately to their habitual nest-sites. We investigated the effects of sensory manipulation on oceanic navigation in Scopoli's shearwaters (Calonectris diomedea) breeding at Pianosa island (Italy), by displacing them 400 km from their colony and tracking them. A recent experiment on Atlantic shearwaters (Cory's shearwater, Calonectris borealis) breeding in the Azores indicated a crucial role of olfaction over the open ocean, but left open the question of whether birds might navigate by topographical landmark cues when available. Our experiment was conducted in the Mediterranean sea, where the availability of topographical cues may provide an alternative navigational mechanism for homing. Magnetically disturbed shearwaters and control birds oriented homeward even when the coast was not visible and rapidly homed. Anosmic shearwaters oriented in a direction significantly different from the home direction when in open sea. After having approached a coastline their flight path changed from convoluted to homeward oriented, so that most of them eventually reached home. Beside confirming that magnetic cues appear unimportant for oceanic navigation by seabirds, our results support the crucial role of olfactory cues for birds' navigation and reveal that anosmic shearwaters are able to home eventually by following coastal features. PMID- 26548947 TI - Constrained growth flips the direction of optimal phenological responses among annual plants. AB - Phenological changes among plants due to climate change are well documented, but often hard to interpret. In order to assess the adaptive value of observed changes, we study how annual plants with and without growth constraints should optimize their flowering time when productivity and season length changes. We consider growth constraints that depend on the plant's vegetative mass: self shading, costs for nonphotosynthetic structural tissue and sibling competition. We derive the optimal flowering time from a dynamic energy allocation model using optimal control theory. We prove that an immediate switch (bang-bang control) from vegetative to reproductive growth is optimal with constrained growth and constant mortality. Increasing mean productivity, while keeping season length constant and growth unconstrained, delayed the optimal flowering time. When growth was constrained and productivity was relatively high, the optimal flowering time advanced instead. When the growth season was extended equally at both ends, the optimal flowering time was advanced under constrained growth and delayed under unconstrained growth. Our results suggests that growth constraints are key factors to consider when interpreting phenological flowering responses. It can help to explain phenological patterns along productivity gradients, and links empirical observations made on calendar scales with life-history theory. PMID- 26548948 TI - Automated Three-Dimensional Reconstruction of the Left Ventricle From Multiple Axis Echocardiography. AB - Two-dimensional echocardiography (echo) is the method of choice for noninvasive evaluation of the left ventricle (LV) function owing to its low cost, fast acquisition time, and high temporal resolution. However, it only provides the LV boundaries in discrete 2D planes, and the 3D LV geometry needs to be reconstructed from those planes to quantify LV wall motion, acceleration, and strain, or to carry out flow simulations. An automated method is developed for the reconstruction of the 3D LV endocardial surface using echo from a few standard cross sections, in contrast with the previous work that has used a series of 2D scans in a linear or rotational manner for 3D reconstruction. The concept is based on a generalized approach so that the number or type (long-axis (LA) or short-axis (SA)) of sectional data is not constrained. The location of the cross sections is optimized to minimize the difference between the reconstructed and measured cross sections, and the reconstructed LV surface is meshed in a standard format. Temporal smoothing is implemented to smooth the motion of the LV and the flow rate. This software tool can be used with existing clinical 2D echo systems to reconstruct the 3D LV geometry and motion to quantify the regional akinesis/dyskinesis, 3D strain, acceleration, and velocities, or to be used in ventricular flow simulations. PMID- 26548949 TI - PRL-3 promotes gastric cancer migration and invasion through a NF-kappaB-HIF 1alpha-miR-210 axis. AB - Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues. In gastric cancer cells, PRL-3 upregulated miR-210 expression in a HIF-1alpha-dependent fashion under normoxia and hypoxia. In addition, PRL-3 activated NF-kappaB signaling and promoted HIF-1alpha expression through modulating phosphorylation of p65. NF-kappaB signaling, HIF-1alpha, and miR-210 partially contributed to PRL 3-induced migration and invasion. Furthermore, the levels of PRL-3, HIF-1alpha, and miR-210 transcripts inversely affected the overall survival of gastric cancer patients. Our work identified the existence of a PRL-3-NF-kappaB-HIF-1alpha-miR 210 axis, thus providing new insight into the role of PRL-3 in promoting gastric cancer invasiveness. KEY MESSAGE: PRL-3 regulates microRNA in gastric cancer. PRL 3 elevates hsa-miR-210 by upregulating HIF-1alpha. PRL-3 activates a NF-kappaB HIF-1alpha-miR-210 axis by enhancing the phosphorylation of p65. PRL-3 promotes cell migration and invasion via the NF-kappaB-HIF-1alpha-miR-210 axis. High levels of PRL-3 and miR-210 are related with poor OS in gastric cancer. PMID- 26548950 TI - Urologic Demise of Astronomer Tycho Brahe: A Cosmic Case of Urinary Retention. PMID- 26548952 TI - [Control of major cardiovascular risk factors of ischemic heart disease in secondary prevention in Aragon: COCINA study]. AB - Ischemic heart disease remains a leading cause of death in Spain. According to the American Heart Association/American College of Cardiology (AHA/ACC) and European national societies, secondary prevention for these patients consists of control of major cardiovascular risk factors (CVRF) and suitable lifestyle habits. OBJECTIVE: To determine the degree of control of CVRF in the Aragonese population in secondary prevention. DESIGN: Cross-sectional study of a sample of 705 patients of Aragon who had suffered a cardiac event, selected opportunistically in consultations of family physicians participating in the 3 provinces of Aragon. The study was conducted in the second half of 2012. INTERVENTION: To measure the degree of control of different FRVC and lifestyle habits in this population. VARIABLES MEASURED: Anthropometric, different cardiovascular risk factors, treatment and lifestyle. RESULTS: 58% of men and 52% of women met criteria for monitoring of measured variables. The best result was obtained with smoking cessation and the worst with BMI. Hypertension, Dyslipidemia and Diabetes Mellitus achieve poor control results. CONCLUSION: The results show that the degree of control of CVRF is still low, especially in variables such as dyslipidemia and Diabetes Mellitus. Only 16.5% of control patients met criteria given the pharmacologically-modifiable cardiovascular risk factors. PMID- 26548953 TI - Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures. AB - Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity. The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions. RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 A resolution, which reveal a closed conformation with base flipping and base specific recognition of RSSs. Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism. Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule. PMID- 26548954 TI - MAJIN Links Telomeric DNA to the Nuclear Membrane by Exchanging Telomere Cap. AB - In meiosis, telomeres attach to the inner nuclear membrane (INM) and drive the chromosome movement required for homolog pairing and recombination. Here, we address the question of how telomeres are structurally adapted for the meiotic task. We identify a multi-subunit meiotic telomere-complex, TERB1/2-MAJIN, which takes over telomeric DNA from the shelterin complex in mouse germ cells. TERB1/2 MAJIN initially assembles on the INM sequestered by its putative transmembrane subunit MAJIN. In early meiosis, telomere attachment is achieved by the formation of a chimeric complex of TERB1/2-MAJIN and shelterin. The chimeric complex matures during prophase into DNA-bound TERB1/2-MAJIN by releasing shelterin, forming a direct link between telomeric DNA and the INM. These hierarchical processes, termed "telomere cap exchange," are regulated by CDK-dependent phosphorylation and the DNA-binding activity of MAJIN. Further, we uncover a positive feedback between telomere attachment and chromosome movement, revealing a comprehensive regulatory network underlying meiosis-specific telomere function in mammals. PMID- 26548955 TI - Examination of the Chicago Multiscale Depression Inventory and Initial Validation of a Positive Scale. AB - The Chicago Multiscale Depression Inventory (CMDI) was developed to improve accuracy in measuring depression symptoms in individuals with non-psychiatric medical illness. Earlier psychometric evaluation of the CMDI has emphasized properties of items that measure negative affect and experience. In this study, we provide an initial evaluation of an outcome scale of positive items that are also included within the CMDI but have previously been excluded from calculation of the total score. Psychometric data for the CMDI negative and positive item subscales were determined in healthy adults and patients with multiple sclerosis. Analysis included measurements of factor structure, reliability, and validity in comparison with other established measures of depression and affect. Study findings indicate that in healthy and patient samples, the CMDI Positive scale has very good reliability and validity. The Positive scale score also appears to predict depression symptoms beyond the negative item scale scores. The CMDI Positive scale could be a valuable clinical and research tool. Inclusion of the Positive scale in the CMDI total score appears to improve the measure by further capturing symptoms of affect and experience that are important to diagnosis of depression and are not covered by the negative scales alone. (JINS, 2016, 22, 76 82). PMID- 26548957 TI - Evaluation of an in vitro muscle contraction model in mouse primary cultured myotubes. AB - To construct an in vitro contraction model with the primary cultured myotubes, we isolated satellite cells from the mouse extensor digitorum longus. Differentiated myotubes possessed a greater number of sarcomere assemblies and higher expression levels of myosin heavy chain, cytochrome c oxidase IV, and myoglobin than in C2C12 myotubes. In agreement with these results regarding the sarcomere assemblies and protein expressions, the primary myotubes showed higher contractile activity stimulated by the electric pulses than that in the C2C12 myotubes. These data suggest that mouse primary myotubes will be a valuable research tool as an in vitro muscle contraction model. PMID- 26548956 TI - Identification of Vibrio cholerae serotypes in high-risk marine products with non gel sieving capillary electrophoresis. AB - Vibrio cholerae, a natural inhabitant of the marine environment, poses a threat to human health, and its new epidemic variants have been reported. A method of multiplex polymerase chain reaction-capillary electrophoresis-laser-induced fluorescence (PCR-CE-LIF) detection has been developed to detect and identify V. cholerae in marine products sensitively, rapidly, and reliably. Four sets of primers were selected to amplify genus-specific VCC gene, O139 serogroup-specific O139 gene, O1 serogroup-specific O1 gene, and ctxA gene associated with the CT toxin of enterotoxigenic V. cholerae. The PCR products were detected using CE-LIF with SYBR Gold serving as the DNA fluorescent dye. The parameters of PCR and the separation conditions of CE-LIF were optimized. Under the optimal conditions, V. cholerae was detected and four serotypes were identified simultaneously within 8 min. The alignment analysis showed that the PCR products had good agreement with the published sequences from GenBank, indicating that the primers selected in this study had high specificity and the PCR results were reliable. The proposed method could detect 5 to 20 cfu/ml V. cholerae. The intraday precisions of migration time and peak area of DNA marker and PCR products were in the ranges of 1.60-2.56% and 1.60-6.29%, respectively. The specificity results showed that only five standard bacteria used in this study showed the specific peaks when the target bacteria were mixed with seven other common intestinal pathogenic bacteria at the same concentration. The assay was applied to 71 high-risk marine products, and different serotypes of V. cholerae could be identified sensitively and reliably. PMID- 26548959 TI - A novel approach for oxidation analysis of therapeutic proteins. AB - Measuring and monitoring of protein oxidation modifications is important for biopharmaceutical process development and stability assessment during long-term storage. Currently available methods for biomolecules oxidation analysis use time consuming peptide mapping analysis. Therefore, it is desirable to develop high throughput methods for advanced process control of protein oxidation. Here, we present a novel approach by which oxidative protein modifications are monitored by an indirect potentiometric method. The method is based on adding an electron mediator, which enhances electron transfer (ET) between all redox species and the electrode surface. Specifically, the procedure involves measuring the sharp change in the open circuit potential (OCP) for the mediator system (redox couple) as a result of its interaction with the oxidized protein species in the solution. Application of Pt and Ag/AgCl microelectrodes allowed for a high-sensitivity protein oxidation analysis. We found that the Ru(NH3)6(2+/3+) redox couple is suitable for measuring the total oxidation of a wide range of therapeutic proteins between 1.1 and 13.6%. Accuracy determined by comparing with the known percentage oxidation of the reference standard showed that percentage oxidation determined for each sample was within +/- 20% of the expected percentage oxidation determined by mass spectrometry. PMID- 26548958 TI - An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells. AB - PolyADP-ribosylation is mediated by poly(ADP-ribose) (PAR) polymerases (PARPs) and may be involved in various cellular events, including chromosomal stability, DNA repair, transcription, cell death, and differentiation. The physiological level of PAR is difficult to determine in intact cells because of the rapid synthesis of PAR by PARPs and the breakdown of PAR by PAR-degrading enzymes, including poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3. Artifactual synthesis and/or degradation of PAR likely occurs during lysis of cells in culture. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the physiological levels of PAR in cultured cells. We immediately inactivated enzymes that catalyze the synthesis and degradation of PAR. We validated that trichloroacetic acid is suitable for inactivating PARPs, PARG, and other enzymes involved in metabolizing PAR in cultured cells during cell lysis. The PAR level in cells harvested with the standard radioimmunoprecipitation assay buffer was increased by 450-fold compared with trichloroacetic acid for lysis, presumably because of activation of PARPs by DNA damage that occurred during cell lysis. This ELISA can be used to analyze the biological functions of polyADP-ribosylation under various physiological conditions in cultured cells. PMID- 26548961 TI - Where does Grapholita molesta (Busck) (Lepidoptera: Tortricidae) overwinter in adjacent peach, pear and apple orchards? AB - The Oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), is a major pest of tree fruits worldwide, and the diapausing larvae overwinter in cryptic habitats. Investigations of overwintering G. molesta were conducted in adjacent peach, pear and apple orchards in Northern China over three consecutive winters to determine the overwintering site and habitat preferences of the moth. Counts of overwintering larvae in the different orchards demonstrated that the late-maturing peach orchard ('Shenzhou honey peach') was the most preferred overwintering habitat with more than 90% of the collected larvae. Larvae were more abundant in host trees, and they very rarely overwintered in the soil. The overwintering site preferences on the host trees were significantly different; over 50% larvae were located in the tree trunks, and followed by main branches. Most of the G. molesta overwintered on the sunny side of the host trees at or below 60 cm from the ground; a few were cocooned on the shaded sides of the trees or greater than 60 cm from the ground. G. molesta began overwintering between August and October, mid- to late September was the peak period for entering winter diapause during 2011-2013 (77.78, 67.59 and 71.15%, respectively). Our findings improve understanding of the orchard habitat and overwintering site preferences of G. molesta and would be useful in the development of efficient forecasting and pest-management strategies for orchards during the winter and early spring. PMID- 26548960 TI - Estimating mRNA lengths from Plasmodium falciparum genes by Virtual Northern RNA seq analysis. AB - Accurate gene models are essential for understanding parasite biology. However, transcript structure information is lacking for most parasite genes. Here, we describe "Virtual Northern" analysis of the malaria parasite Plasmodium falciparum to address this issue. RNA-seq libraries were made from size fractionated RNA. Transcript sizes for 3052 genes were inferred from the read counts in each library. The data show that for almost half of the transcripts, the combined untranslated regions are more than twice the length of the open reading frame. Furthermore, we identified novel polycistronic, or gene overlapping, transcripts that suggest revisions to current gene models are needed. PMID- 26548962 TI - Downregulation of matrix metalloproteinase-19 induced by respiratory syncytial viral infection affects the interaction between epithelial cells and fibroblasts. AB - The present study was designed to examine the expression and function of matrix metalloproteinase-19 (MMP-19), which is downregulated following respiratory syncytial virus (RSV) infection. The diverse expression levels of MMP were examined using a designed cDNA expression array. The expression and secretion of MMP-19 was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. The proliferation of epithelial cells and lung fibroblasts were examined using flow cytometry. The epithelial-mesenchymal transition (EMT) was also examined by performing western blot and RT-qPCR analyses. The results of the cDNA assay showed that infection with RSV resulted in the abnormal expression of certain metalloproteinases. Among these, the expression of MMP-19 decreased 3 and 7 days following infection. By using flow cytometric, western blot and RT-qPCR analyses, the present study demonstrated that the downregulation of MMP-19 inhibited the proliferation of epithelial cells, promoted the EMT and induced the proliferation of lung fibroblasts. Taken together, the findings of the present study suggested that the downregulation of MMP-19 following RSV infection may be associated with the development of airway hyper-responsiveness. PMID- 26548963 TI - Recurrence of Pain After Usual Nonoperative Care for Symptomatic Lumbar Disk Herniation: Analysis of Data From the Spine Patient Outcomes Research Trial. AB - OBJECTIVE: To determine risks and predictors of recurrent leg and low back pain (LBP) after unstructured, usual nonoperative care for subacute/chronic symptomatic lumbar disk herniation (LDH). DESIGN: Secondary analysis of data from a concurrent randomized trial and observational cohort study. SETTING: Thirteen outpatient spine practices. PARTICIPANTS: A total of 199 participants with resolution of leg pain and 142 participants with resolution of LBP from among 478 participants receiving usual nonoperative care for symptomatic LDH. ASSESSMENT OF RISK FACTORS: Potential predictors of recurrence included time to initial symptom resolution, sociodemographics, clinical characteristics, work-related factors, imaging-detected herniation characteristics, and baseline pain bothersomeness. MAIN OUTCOME MEASUREMENTS: Leg pain and LBP bothersomeness were assessed by the use of a 0-6 numerical scale at up to 4 years of follow-up. For individuals with initial resolution of leg pain, we defined recurrent leg pain as having leg pain, receiving lumbar epidural steroid injections, or undergoing lumbar surgery subsequent to initial leg pain resolution. We calculated cumulative risks of recurrence by using Kaplan-Meier survival plots and examined predictors of recurrence using Cox proportional hazards models. We used similar definitions for LBP recurrence. RESULTS: One- and 3-year cumulative recurrence risks were 23% and 51% for leg pain, and 28% and 70% for LBP, respectively. Early leg pain resolution did not predict future leg pain recurrence. Complete leg pain resolution (adjusted hazard ratio [aHR] 0.47, 95% confidence interval [CI] 0.31 0.72) and posterolateral herniation location (aHR 0.61; 95% CI 0.39-0.97) predicted a lower risk of leg pain recurrence, and joint problems (aHR 1.89; 95% CI 1.16-3.05) and smoking (aHR 1.81; 95% CI 1.07-3.05) predicted a greater risk of leg pain recurrence. For participants with complete initial resolution of pain, recurrence risks at 1 and 3 years were 16% and 41% for leg pain and 24% and 59% for LBP, respectively. CONCLUSIONS: Recurrence of pain is common after unstructured, usual nonsurgical care for LDH. These risk estimates depend on the specific definitions applied, and the predictors identified require replication in future studies. PMID- 26548964 TI - Update on Brain Tumors: New Developments in Neuro-oncologic Diagnosis and Treatment, and Impact on Rehabilitation Strategies. AB - Brain tumors can be a source of functional impairment to patients due to neurologic sequelae associated with the tumor itself as well as treatment side effects. As a result, many of these patients may require rehabilitation services. Surgery, chemotherapy, and radiation therapy have been longstanding, primary treatment modalities in the management of brain tumors, though these treatments continue to evolve given new developments in research and technology. A better understanding of the diagnostic workup and current treatment standards helps the physiatrist and rehabilitation team identify rehabilitation services needed, recognize potential side-effects from anticipated or concurrent treatments, and coordinate care with referral sources. The purpose of this article is to review these new advances in diagnosis and treatment of patients with brain tumors, as well as discuss the rehabilitation implications for this population, including factors such as rehabilitation approach, timing of concomitant treatment, cost management, and coordination of care. PMID- 26548965 TI - Ultrasound-Guided Scraping for Chronic Patellar Tendinopathy: A Case Presentation. AB - Chronic patellar tendinopathy is a common complaint among athletes who repetitively stress the extensor mechanism of the knee. Multiple treatment options have been described, but evidence is lacking, specifically when eccentric loading has failed. Debate continues regarding the patho-etiology of chronic patellar tendon pain. There has been recent interest regarding the neurogenic influences involved in chronic tendinopathy, and interventions targeting neovessels and accompanying neonerves have shown promise. This is the first description of an ultrasound-guided technique in which the neovessels and accompanying neonerves in patellar tendinopathy were targeted using a needle scraping technique of the posterior surface of the patellar tendon. PMID- 26548966 TI - Thoracic Radiculopathy Resulting From Retrograde Neuronal Degeneration. AB - We report a case of thoracic radiculopathy caused by retrograde degeneration from an intercostal nerve mass. A 74-year-old woman presented with thoracic radicular pain in the T4 dermatome. Needle electromyography revealed abnormal spontaneous activity in the left paraspinal muscle. Magnetic resonance imaging of the thoracic spine showed no signs of a herniated thoracic disk or root compression but revealed a mass along the intercostal space. The pathologic findings included perineural infiltration. A mass located along the intercostal space approximately 1.8 cm from the dorsal root ganglion may cause thoracic radiculopathy via retrograde degeneration. PMID- 26548968 TI - Delayed Sciatic Nerve Injury Resulting From Myositis Ossificans Traumatica. AB - A motorcyclist sustained multiple-system trauma, including a left buttock hematoma requiring decompression and evacuation. Presentation for severe hip pain and lower extremity weakness was delayed. Imaging revealed myositis ossificans traumatica compressing the sciatic nerve in the buttock. The patient underwent sciatic nerve decompression with resection of heterotopic calcification, resulting in improvement in pain and left lower extremity function. This case illustrates the contrast in differential diagnosis of peripheral nerve injury immediately posttrauma and that occurring in a slow, delayed fashion posttrauma. Myositis ossificans may be an underrecognized complication of trauma but should be considered in cases of delayed peripheral nerve injury after trauma. PMID- 26548967 TI - Dynamic Ultrasonography of the Deep External Rotator Musculature of the Hip: A Descriptive Study. AB - BACKGROUND: No detailed reports exist describing the methodology of ultrasound image acquisition of the deep external rotator muscles of the hip. Because gluteal pain and sciatica are common, ultrasound may be a useful dynamic imaging adjunct in the evaluation of these patients. OBJECTIVE: To describe dynamic ultrasonography of the deep external rotator muscles of the hip for diagnostic purposes. DESIGN: Descriptive. SETTING: University radiology department. PARTICIPANTS: Participants (n = 25; 14 male) without gluteal pain or sciatica were enrolled (mean age 27.6 +/- 4.7 years; mean body mass index 26.0 +/- 4.1 kg/m(2)). METHODS: Ultrasonographic cine clips oriented to the long axis of each deep external rotator muscle were captured. In addition, cine clips of the piriformis tendon and obturator internus tendon were obtained. Cine clips were analyzed approximately 1 week after completion of image acquisition independently by 2 blinded raters. MAIN OUTCOME MEASURES: A 5-point Likert scale to evaluate the diagnostic utility of the ultrasound image. RESULTS: The modal Likert scores for rater 1 were as follows: piriformis muscle = 4; piriformis tendon = 4; superior gemellus muscle = 3; obturator internus muscle = 4; obturator internus tendon = 4; inferior gemellus muscle = 4; quadratus femoris muscle = 4. The modal scores for rater 2 were: piriformis muscle = 4; piriformis tendon = 3; superior gemellus muscle = 4; obturator internus muscle = 3; obturator internus tendon = 4; inferior gemellus muscle = 3; quadratus femoris muscle = 4. CONCLUSION: Dynamic ultrasonography may be useful to image the hip deep external rotator musculature for diagnostic purposes and therefore aid in the evaluation of gluteal pain and sciatica. Future work should investigate the reliability and validity of ultrasonography in the evaluation of pathology of these muscles. PMID- 26548969 TI - The Swedish Aging With Spinal Cord Injury Study (SASCIS): Methodology and Initial Results. AB - BACKGROUND: Advances in acute treatment, physiatric care, and rehabilitation have improved survival greatly after spinal cord injury (SCI) and increased longevity. This has led to a need for an in-depth understanding of factors associated with healthy aging in people with long-term SCI. OBJECTIVE: To present the methodology and initial results of the Swedish Aging with Spinal Cord Injury Study, a longitudinal cohort survey targeting older adults with long-term SCI. DESIGN: Cross-sectional cohort study. SETTING: Home and community settings. PARTICIPANTS: People aged 50 years or older with SCI for at least 10 years. METHODS: Data were collected through interviews and assessments during home visits and from the participants' medical records. MAIN OUTCOME MEASUREMENTS: Study-specific protocol with custom-designed questions, and validated generic and SCI-specific assessment tools focusing on functioning, disability, health, well-being, lifestyle, and personal and environmental factors. RESULTS: Of 795 potential participants, 184 matched the inclusion criteria and the final sample comprised 123 participants (67% response rate; 36 women and 87 men, mean age 63 +/- 9 years, mean time since injury 24 +/- 12 years). Traumatic SCI accounted for 62%, and 31% had sustained a complete SCI. A majority was married or had a partner, and used some form of assistance and/or mobility device. Thirty-five percent were working full-time or part-time. Based on the American Spinal Injury Association Impairment Scale (AIS), 3 groups of SCI severity were formed. There were no significant differences in chronological age, marital status, or vocational situation between the tetraplegia AIS A-C group (n = 22), the paraplegia AIS A-C group (n = 41), and the all AIS D group (n = 60). Participants in the all AIS D group were significantly older at injury, had a shorter time since injury, and were less likely to use mobility devices compared with the other 2 groups. CONCLUSION: These baseline data of the Swedish Aging with Spinal Cord Injury Study provide a description of older adults with long-term SCI. Forthcoming studies and subsequent follow-ups will generate new insights into factors that promote healthy aging, minimize disability and enhance participation, quality of life, and life satisfaction in people aging with long-term SCI. PMID- 26548970 TI - Ginsenoside Rb1 Attenuates Acute Inflammatory Nociception by Inhibition of Neuronal ERK Phosphorylation by Regulation of the Nrf2 and NF-kappaB Pathways. AB - Ginsenoside-Rb1 (Rb1) has anti-inflammatory effects. However, the potential antinociceptive value of Rb1 for the treatment of acute inflammatory nociception is still unknown. In this study, we examined whether Rb1 has any antinociceptive effects on acute inflammatory nociception in Sprague Dawley rats given intrathecal (i.t.) introduction of Rb1 (2, 10, and 50 MUg) 20 minutes before injection of formalin (5%, 50 MUL) into the plantar surface of the hind paws. I.t. introduction of Rb1 significantly decreased nociceptive behavior during phase II (16-60 minutes), but not phase I (0-10 minutes), after formalin stimulation, corresponding to the reduced activation of c-Fos in the L4 to L5 spinal dorsal horn after formalin stimulation. Rb1 also reduced the phosphorylation of extracellular signal-regulated kinase in the neurons, but not the microglia and astrocytes. Microscopic examination of the microglia and astrocytes revealed no morphological changes due to formalin stimulation and i.t. introduction of Rb1. Interestingly, Rb1 activated the nuclear factor erythroid 2 related factor 2 pathway and inhibited nuclear factor kappa B pathways. PERSPECTIVE: Our findings indicate that i.t. introduction of Rb1 might effectively inhibit formalin-induced acute inflammatory nociception by inhibition of neuronal extracellular signal-regulated kinase phosphorylation, which is thought to regulate the nuclear factor erythroid 2-related factor 2 nuclear factor kappa B pathways in the spinal dorsal horn, which suggests therapeutic potential for suppression of acute inflammatory pain. PMID- 26548972 TI - Reorganized Trunk Muscle Activity During Multidirectional Floor Perturbations After Experimental Low Back Pain: A Comparison of Bilateral Versus Unilateral Pain. AB - Low back pain changes trunk muscle activity after external perturbations but the relationship between pain intensities and distributions and their effect on trunk muscle activity remains unclear. The effects of unilateral and bilateral experimental low back pain on trunk muscle activity were compared during unpredictable multidirectional surface perturbations in 19 healthy participants. Pain intensity and distribution were assessed using a visual analogue scale (VAS) and pain drawings. Root mean square (RMS) of the electromyographic (EMG) signals from 6 trunk muscles bilaterally after each perturbation was extracted and averaged across perturbations. The difference (DeltaRMS-EMG) and absolute difference (absolute DeltaRMS-EMG) RMS from baseline conditions were extracted for each muscle during pain conditions and averaged bilaterally for back and abdominal muscle groups. Bilateral compared with unilateral pain induced higher VAS scores (P < .005) and larger pain areas (P < .001). Significant correlation was present between VAS scores and muscle activity during unilateral (P < .001) and bilateral pain (P < .001). Compared with control injections DeltaRMS-EMG increased in the back (P < .03) and abdominal (P < .05) muscles during bilateral and decreased in the back (P < .01) and abdominal (P < .01) muscles during unilateral pain. Bilateral pain caused greater absolute DeltaRMS-EMG changes in the back (P < .01) and abdominal (P < .01) muscle groups than unilateral pain. PERSPECTIVE: This study provided novel observations of differential trunk muscle activity in response to perturbations dependent on pain intensity and/or pain distribution. Because of complex and variable changes the relevance of clinical examination of muscle activity during postural tasks is challenged. PMID- 26548971 TI - The Influence of Chronic Pain on Postoperative Pain and Function After Hip Surgery: A Prospective Observational Cohort Study. AB - Pre-existing or chronic pain is an established risk factor for severe postoperative pain. In this prospective observational cohort study, we investigated whether a history of chronic pain, beyond the presence of hip related pain, affected other postoperative factors including early mobilization, function, and psychological distress after hip surgery. Patients who underwent total hip replacement surgery were observed from the preoperative day until the seventh postoperative day. Before surgery, they were characterized by their pain history, pain intensity, function, and psychological characteristics. Postoperatively, pain intensity was evaluated on day 1, 3, 5, and 7 and the analgesic consumption was recorded for each of these days. Measures of function (functional questionnaire, ability to mobilize and to climb stairs, and range of hip motion) and psychological distress were re-evaluated on day 7. A history of chronic pain was associated with slower postoperative mobilization, poorer physical function, and greater psychological distress in addition to increased postoperative pain intensity. The comorbidity of a chronic pain disorder resulted in greater pain intensity after surgery, and also impeded postoperative rehabilitation. Identification of patients with a chronic pain disorder is necessary preoperatively so that appropriate pain management and rehabilitation can be planned to facilitate recovery. PERSPECTIVE: Chronic pain, beyond the presence of hip-related pain, is associated with slower postoperative mobilization, poorer physical function, and greater psychological distress after total hip replacement surgery. Identification of patients with chronic pain and establishment of multiprofessional perioperative management might improve postoperative rehabilitation of patients with chronic pain. PMID- 26548974 TI - Reactivity of functionalized indoles with rare-earth metal amides. Synthesis, characterization and catalytic activity of rare-earth metal complexes incorporating indolyl ligands. AB - The reactivity of several functionalized indoles 2-(RNHCH2)C8H5NH (R = C6H5 (1), (t)Bu (2), 2,6-(i)Pr2C6H3 (3)) with rare-earth metal amides is described. Reactions of 1 or 2 with [(Me3Si)2N]3RE(MU-Cl)Li(THF)3 (RE = Eu, Yb) respectively produced the europium complexes [2-(C6H5N[double bond, length as m dash]CH)C8H5N]2Eu[N(SiMe3)2] (4) and [2-((t)BuN[double bond, length as m dash]CH)C8H5N]Eu[N(SiMe3)2]2 (5), and the ytterbium complex [2-((t)BuN[double bond, length as m-dash]CH)C8H5N]2Yb[N(SiMe3)2] (6), containing bidentate anionic indolyl ligands via dehydrogenation of the amine to the imine. In contrast, reactions of the more sterically bulky indole 3 with [(Me3Si)2N]3RE(MU Cl)Li(THF)3 afforded complexes [2-(2,6-(i)Pr2C6H3NCH2)C8H5N]RE[N(SiMe3)2](THF)2 (RE = Yb (7), Y (8), Er (9), Dy (10)) with the deprotonated indolyl ligand. While reactions of 3 with yttrium and ytterbium amides in refluxing toluene respectively gave the complexes [2-(2,6-(i)Pr2C6H3N[double bond, length as m dash]CH)C8H5N]3Y (11) and [2-(2,6-(i)Pr2C6H3N[double bond, length as m dash]CH)C8H5N]2Yb(II)(THF)2 (12), along with transformation of the amino group to the imino group, and also with a reduction of Yb(3+) to Yb(2+) in the formation of 12. Reactions of 3 with samarium and neodymium amides provided novel dinuclear complexes {[MU-eta(5):eta(1):eta(1)-2-(2,6-(i)Pr2C6H3NCH2)C8H5N]RE[N(SiMe3)2]}2 (RE = Sm (13), Nd (14)) having indolyl ligands in MU-eta(5):eta(1):eta(1) hapticities. The pathway for the transformation of the amino group to the imino group is proposed on the basis of the experimental results. The new complexes displayed excellent activity in the intramolecular hydroamination of aminoalkenes. PMID- 26548973 TI - Mimicking the phosphorylation of Rsp5 in PKA site T761 affects its function and cellular localization. AB - Rsp5 ubiquitin ligase belongs to the Nedd4 family of proteins, which affect a wide variety of processes in the cell. Here we document that Rsp5 shows several phosphorylated variants of different mobility and the migration of the phosphorylated forms of Rsp5 was faster for the tpk1Delta tpk3Delta mutant devoid of two alternative catalytic subunits of protein kinase A (PKA), indicating that PKA possibly phosphorylates Rsp5 in vivo. We demonstrated by immunoprecipitation and Western blot analysis of GFP-HA-Rsp5 protein using the anti-phospho PKA substrate antibody that Rsp5 is phosphorylated in PKA sites. Rsp5 contains the sequence 758-RRFTIE-763 with consensus RRXS/T in the catalytic HECT domain and four other sites with consensus RXXS/T, which might be phosphorylated by PKA. The strain bearing the T761D substitution in Rsp5 which mimics phosphorylation grew more slowly at 28 degrees C and did not grow at 37 degrees C, and showed defects in pre-tRNA processing and protein sorting. The rsp5-T761D strain also demonstrated a reduced ability to form colonies, an increase in the level of reactive oxygen species (ROS) and hypersensitivity to ROS-generating agents. These results indicate that PKA may downregulate many functions of Rsp5, possibly affecting its activity. Rsp5 is found in the cytoplasm, nucleus, multivesicular body and cortical patches. The rsp5-T761D mutation led to a strongly increased cortical localization while rsp5-T761A caused mutant Rsp5 to locate more efficiently in internal spots. Rsp5-T761A protein was phosphorylated less efficiently in PKA sites under specific growth conditions. Our data suggests that Rsp5 may be phosphorylated by PKA at position T761 and that this regulation is important for its localization and function. PMID- 26548975 TI - Intra-tumor distribution of PEGylated liposome upon repeated injection: No possession by prior dose. AB - Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid tumors. However, significant variability has been detected in their intra-tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-tumor accumulation and distribution of weekly sequentially administered oxaliplatin (l-OHP)-containing PEGylated liposomes. In that study, the first and second doses of l-OHP containing PEGylated liposomes were distributed diversely and broadly within tumor tissues, resulting in a potent anti-tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-tumor accumulation and distribution of "empty" PEGylated liposomes. Intra-tumor distribution of sequentially administered "empty" PEGylated liposomes was altered in a dosing interval-dependent manner. In addition, the intra-tumor distribution pattern was closely related to the chronological alteration of tumor blood flow as well as vascular permeability in the growing tumor tissue. These results suggest that the sequential administrations of PEGylated liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems. PMID- 26548976 TI - Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models. AB - Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 MUg/h in vitro and 1.0 MUg/h in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration time curve of 3049 ng day/mL with the microdevice vs. 2118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy. PMID- 26548977 TI - [The health of adults undergoing an eviction process]. AB - OBJECTIVE: To analyze perceived health status and other health-related indicators in the adult population in Granada (Spain) undergoing an eviction process from their homes, whether rented or owned, in comparison with health indicators in the general adult population in Andalusia. METHODS: A cross-sectional survey was administered by trained staff. The survey included instruments from the Andalusian Health Survey 2011 for measuring variables related to physical and mental health, as well as health-related habits. We compared the results with those obtained from the Andalusian general population through the Andalusian Health Survey. A bivariate analysis using the chi2 test and a multivariate logistic regression analysis were conducted. RESULTS: We obtained a total sample of 205 people in the process of eviction. A total of 59.5% (n=122) were women, and 40.5% (n=83) were men. Participants were more likely to have poor health (odds ratio [OR]: 12.63, 95% confidence interval [95%CI]: 8.74-18.27), have cardiovascular diseases (OR: 3.08; 95%CI: 1.54- 6.16), or to smoke (OR: 1.68; 95% CI: 1.21-2.33) compared with the Andalusian general population. Most of the health indicators analyzed showed a worse outcome for women undergoing an eviction process. CONCLUSIONS: Our results suggest that, in the current context of economic crisis, people undergoing a process of eviction in Granada and its metropolitan area show poorer health than the Andalusian general population. Further research is needed on health and evictions from different methodological approaches, for a better understanding of the topic. PMID- 26548979 TI - Narcissistic vulnerability is a common cause for depression in patients with Gilles de la Tourette syndrome. AB - The aim of this study was to assess for the first time different dimensions of narcissistic self-regulation in a large cohort of adult patients with Gilles de la Tourette syndrome (GTS) (n=50). From preliminary studies it is suggested that narcissistic personality trait and disorder, respectively, are relatively uncommon and occur in only 6-10% of GTS patients. In this study we used the Narcissism Inventory (NI), a 163-items questionnaire that measures four different dimensions of narcissism. The main result was that the prevalence of narcissism strongly depends on the subtype of narcissism: while the vulnerable narcissism ("threatened self" and "hypochondriac self") was common, the "classic narcissistic self" (grandiose narcissism) was rare. From our data an association between comorbid depression and increased values of the "threatened self" and comorbid OCD with increased values of the "hypochondriac self" is suggested. Narcissism correlated positively with the personality domain neuroticism and had a significantly negative impact on patients' quality of life. Therefore it can be speculated that vulnerable narcissism is - among several others - one cause for depression in patients with GTS. These findings may open new psychotherapeutic perspectives in the treatment of depression in patients with GTS. PMID- 26548978 TI - The behavior of compression and degradation for municipal solid waste and combined settlement calculation method. AB - The total compression of municipal solid waste (MSW) consists of primary, secondary, and decomposition compressions. It is usually difficult to distinguish between the three parts of compressions. In this study, the odeometer test was used to distinguish between the primary and secondary compressions to determine the primary and secondary compression coefficient. In addition, the ending time of the primary compressions were proposed based on municipal solid waste compression tests in a degradation-inhibited condition by adding vinegar. The amount of the secondary compression occurring in the primary compression stage has a relatively high percentage to either the total compression or the total secondary compression. The relationship between the degradation ratio and time was obtained from the tests independently. Furthermore, a combined compression calculation method of municipal solid waste for all three parts of compressions including considering organics degradation is proposed based on a one-dimensional compression method. The relationship between the methane generation potential L0 of LandGEM model and degradation compression index was also discussed in the paper. A special column compression apparatus system, which can be used to simulate the whole compression process of municipal solid waste in China, was designed. According to the results obtained from 197-day column compression test, the new combined calculation method for municipal solid waste compression was analyzed. The degradation compression is the main part of the compression of MSW in the medium test period. PMID- 26548980 TI - Associations between self-esteem, anxiety and depression and metacognitive awareness or metacognitive knowledge. AB - This study explored in a non-clinical sample the associations between self esteem, anxiety and depression symptoms and metacognitive awareness or metacognitive knowledge. Higher metacognitive awareness scores measured during the neuropsychological tasks were positively associated with higher depression scores in the social cognition test. Metacognitive knowledge score measured independently of ongoing neuropsychological tasks was positively associated with lower self-esteem, higher anxiety (state or trait) and depression scores. PMID- 26548981 TI - Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression. AB - Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3-4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3-4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder. PMID- 26548982 TI - Circulating anti-brain autoantibodies in schizophrenia and mood disorders. AB - In recent years, an inflammatory autoimmune process, autoantibodies mediated, has been porposed as having a role in the development of different psychiatric disorders. The aim of this study was to assay organ-specific and non organ specific circulating autoantibodies in schizophrenia, mood disorders and healthy controls; among organ-specific autoantibodies we focused on different fluorescence patterns of anti-brain autoantibodies against rat and monkey's sections of hippocampus, hypothalamus and cerebellum. Serum samples from 50 acutelly ill patients (30 schizophrenia and 20 mood disorders) and from 20 healthy controls were collected. Autoantibodies were assayed by indirect immunofluorescence, enzyme linked immunosorbent assay and chemiluminescence immunoassay. We found a significant difference for circulating autoantibodies to hypothalamus, hippocampus and cerebellum and for anti-nuclear autoantibodies in both schizophrenia and mood disorders when compared to the control group. Referring to the two groups of patients only, circulating antibodies anti hypothalamus were found significant higher in mood disorders rather than in schizophrenia, with specific regard to nuclear and cytoplasmic staining of the neurons. These data suggest an aspecific diffuse brain involvement of anti-brain autoantibodies in acute phases of schizophrenia and mood disorders. The greater involvement of the hypothalamus in mood disorders highlights the close relationship between autoimmunity, hypothalamic-pituitary-adrenal axis and affective disorders. PMID- 26548983 TI - Predictive value of neutrophil-lymphocyte ratio in non-muscle-invasive bladder cancer. PMID- 26548984 TI - [Cardiac rehabilitation after myocardial infarction]. AB - Although the proofs of the benefits of cardiac rehabilitation accumulate, many patients are not sent to rehabilitation units, especially younger and very elderly patients. As the length of stay in acute care units decreases, rehabilitation offers more time to fully assess the patients' conditions and needs. Meta-analyses of randomised trials suggest that mortality can be improved by as much as 20-30%. In addition, rehabilitation helps managing risk factors, including hyperlipidemia, diabetes, smoking and sedentary behaviours. Physical training also helps improving exercise capacity. Because of all of these effects, cardiac rehabilitation for post-myocardial infarction patients has been given a class IA recommendation in current guidelines. PMID- 26548985 TI - The potential of anti-malarial compounds derived from African medicinal plants, part III: an in silico evaluation of drug metabolism and pharmacokinetics profiling. AB - BACKGROUND: Malaria is an endemic disease affecting many countries in Tropical regions. In the search for compound hits for the design and/or development of new drugs against the disease, many research teams have resorted to African medicinal plants in order to identify lead compounds. Three-dimensional molecular models were generated for anti-malarial compounds of African origin (from 'weakly' active to 'highly' active), which were identified from literature sources. Selected computed molecular descriptors related to absorption, distribution, metabolism, excretion and toxicity (ADMET) of the phytochemicals have been analysed and compared with those of known drugs in order to access the 'drug likeness' of these compounds. RESULTS: In the present study, more than 500 anti malarial compounds identified from 131 distinct medicinal plant species belonging to 44 plant families from the African flora have been considered. On the basis of Lipinski's 'Rule of Five', about 70% of the compounds were predicted to be orally bioavailable, while on the basis of Jorgensen's 'Rule of Three', a corresponding >80% were compliant. An overall drug-likeness parameter indicated that approximately 55% of the compounds could be potential leads for the development of drugs. CONCLUSIONS: From the above analyses, it could be estimated that >50% of the compounds exhibiting anti-plasmodial/anti-malarial activities, derived from the African flora, could be starting points for drug discovery against malaria. The 3D models of the compounds have been included as an accompanying file and could be employed in virtual screening. PMID- 26548986 TI - Cytotoxic compounds from Laurencia pacifica. AB - BACKGROUND: The current investigation sought to explore the nature of the secondary metabolites in the algae, Laurencia pacifica. RESULTS: This report details the first isolation of the sesquiterpenes isoaplysin (1), isolaurenisol (2), debromoisolaurinterol (3), debromoaplysinol (4), laur-11-en-10-ol (5), 10alpha-hydroxyldebromoepiaplysin (6), and the previously unknown 10-bromo 3,7,11,11-tetramethylspiro[5.5]undeca-1,7-dien-3-ol (7) from the algae, Laurencia pacifica. Isoaplysin (1) and debromoaplysinol (4) showed promising levels of growth inhibition against a panel cancer-derived cell lines of colon (HT29), glioblastoma (U87, SJ-G2), breast (MCF-7), ovarian (A2780), lung (H460), skin (A431), prostate (Du145), neuroblastoma (BE2-C), pancreas (MIA), murine glioblastoma (SMA) origin with average GI50 values of 23 and 14 MUM. CONCLUSIONS: Isoaplysin (1) and debromoaplysinol (4) were up to fourfold more potent in cancer derived cell populations than in non-tumor-derived normal cells (MCF10A). These analogues are promising candidates for anticancer drug development. Graphical Abstract ?. PMID- 26548987 TI - An expeditious green route toward 2-aryl-4-phenyl-1H-imidazoles. AB - BACKGROUND: Azaheterocycles are an important class of compounds because of their highly potent medicinal activities, and the imidazole subcategory is of special interest in regard to drug discovery research. FINDINGS: An expeditious synthetic protocol of 2-aryl-4-phenyl-1H-imidazoles has been accomplished by reacting phenylglyoxal monohydrate, ammonium acetate, and aldehyde under sonication. Following this green approach a series of 2-aryl-4-phenyl-1H-imidazoles has been synthesized using diversely substituted aldehydes. CONCLUSIONS: A rapid and simple synthetic procedure to synthesize diversely substituted 2-aryl-4-phenyl-1H imidazoles has been reported. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and minimum wastes. The present procedure may find application in the synthesis of biologically active molecules. Graphical Abstract An expeditious synthetic protocol of 2-aryl-4-phenyl-1H imidazoles has been accomplished by reacting phenylglyoxal monohydrate, ammonium acetate, and diversely substituted aldehydes under sonication. PMID- 26548988 TI - Synthesis and antileishmanial evaluation of some 2,3-disubstituted-4(3H) quinazolinone derivatives. AB - BACKGROUND: Leishmaniasis is a neglected tropical parasitic diseases affecting millions of people around the globe. Quinazolines are a group of compounds with diverse pharmacological activities. Owing to their promising antileishmanial activities, some 3-aryl-2-(substitutedstyryl)-4(3H)-quinazolinones were synthesized in good yields (65.2% to 86.4%). RESULTS: The target compounds were synthesized by using cyclization, condensation, and hydrolysis reactions. The structures of the synthesized compounds were determined using elemental microanalysis, infrared (IR), and proton nuclear magnetic resonance ((1)H NMR). The in vitro antileishmanial activities of the synthesized compounds were evaluated using Leishmania donovani strain. All the synthesized compounds displayed appreciable antileishmanial activities (IC50 values, 0.0128 to 3.1085 MUg/ml) as compared to the standard drug miltefosine (IC50 = 3.1911 MUg/ml). (E) 2-(4-chlorostyryl)-3-p-tolyl-4(3H)-quinazolinone (7) is the compound with the most promising antileishmanial activities (IC50 = 0.0128 MUg/ml) which is approximately 4 and 250 times more active than the standard drugs amphotericin B deoxycholate (IC50 = 0.0460 MUg/ml) and miltefosine (IC50 = 3.1911 MUg/ml), respectively. CONCLUSIONS: The results obtained from this investigation indicate that the synthesized and biologically evaluated quinazoline compounds showed promising antileishmanial activities and are good scaffolds for the synthesis of different antileishmanial agents. PMID- 26548989 TI - Chemical composition of ethanol extract of Macrotyloma uniflorum (Lam.) Verdc. using GC-MS spectroscopy. AB - BACKGROUND: Macrotyloma uniflorum Linn (Fabaceae) is a herbaceous plant with annual branches. It is used in kidney stones, inflamed joints, fever, musculoskeletal disorders, sinus wounds and localized abdominal tumors. It is reported as an antioxidant and nutraceutical (forage and food). GC-MS analysis of ethanol extract has led to identification of twenty-eight compounds from M. uniflorum by comparison of their retention indices and mass spectra fragmentation patterns with those stored on the GC-MS computer library. RESULTS: The main constituents identified were mome inositol, ethyl alpha-d-glucopyranoside, n- hexadecanoic acid, linoleic acid (9, 12-octadecadienoic acid), its esters and ethyl derivatives, Vitamin E, stigmasterol and 3-beta-stigmast-5-en-3-ol. CONCLUSIONS: The extracts are rich in linoleic acid and its esters, mome inositol and ethyl alpha-d-glucopyranoside; therefore, this plant can be medicinally beneficial as an antioxidant, in diabetes and its related disorders. PMID- 26548990 TI - Synthesis and biological evaluation of benzimidazole-linked 1,2,3-triazole congeners as agents. AB - BACKGROUND: Benzimidazoles and triazoles are useful structures for research and development of new pharmaceutical molecules and have received much attention in the last decade because of their highly potent medicinal activities. FINDINGS: A simple and efficient synthesis of triazole was carried out by treatment of 2-(4 azidophenyl)-1H-benzo[d]imidazole (6) with different types of terminal alkynes in t-BuOH/H2O, sodium ascorbate, and Zn(OTf)2, screened for cytotoxicity assay and achieved good results. A series of new benzimidazole-linked 1,2,3-triazole (8a-i) congeners were synthesized through cyclization of terminal alkynes and azide. These synthesized congeners 8a-i were evaluated for their cytotoxicity against five human cancer cell lines. These benzimidazole-linked 1,2,3-triazole derivatives have shown promising activity with IC50 values ranging from 0.1 to 43 MUM. Among them, the compounds (8a, 8b, 8c, and 8e) showed comparable cytotoxicity with adriamycin control drug. CONCLUSIONS: In conclusion, we have developed a simple, convenient, and an efficient convergent approach for the synthesis of benzimidazole-linked 1,2,3-triazole congeners as agents. Graphical Abstract Synthesis of 1,2,3-triazole derivatives. PMID- 26548991 TI - Method development and validation of potent pyrimidine derivative by UV-VIS spectrophotometer. AB - BACKGROUND: A rapid and sensitive ultraviolet-visible (UV-VIS) spectroscopic method was developed for the estimation of pyrimidine derivative 6-Bromo-3-(6 (2,6-dichlorophenyl)-2-(morpolinomethylamino) pyrimidine4-yl) -2H-chromen-2-one (BT10M) in bulk form. RESULTS: Pyrimidine derivative was monitored at 275 nm with UV detection, and there is no interference of diluents at 275 nm. The method was found to be linear in the range of 50 to 150 MUg/ml. The accuracy and precision were determined and validated statistically. The method was validated as a guideline. CONCLUSIONS: The results showed that the proposed method is suitable for the accurate, precise, and rapid determination of pyrimidine derivative. Graphical Abstract Method development and validation of potent pyrimidine derivative by UV spectroscopy. PMID- 26548992 TI - Synthesis of 2-cyclopropyl-3-(5-aryl-1H-pyrazol-3-yl)-1,8-naphthyridine. AB - BACKGROUND: 1,8-Naphthyridine derivatives have attracted considerable attention because the 1,8-naphthyridine skeleton is present in many compounds that have been isolated from natural substances, with various biological activities. FINDINGS: N,N-dimethoxy-N-methyl-1,8-naphthyridine-3-carboxamide (1) on reaction with Grignard reagent forms 2-methoxy-1,8-naphthyridine-3-carbaldehyde (2). Compound 2 on reaction with different aromatic aldehydes provided 1-(2 cyclopropyl-1,8-naphthyridin-3-yl)-3-arylprop-2-en-1-ones (3a-e) and these compounds on cyclisation with hydrazine hydrate 99% yielded 2-cyclopropyl-3-(5 aryl-1H-pyrazol-3-yl)-1,8-naphthyridines (4-a-e). Synthesis of the target compounds involved the formation of 4a-e. It was accomplished using Grignard reaction, condensation reaction, and cyclisation reactions. All the synthesized compounds were readily soluble in DMSO. Spectral data of the synthesized compounds were in full agreement with the proposed structures. CONCLUSIONS: In conclusion, we have developed a simple and an efficient Synthesis of 2 cyclopropyl-3-(5-aryl-1H-pyrazol-3-yl)-1,8-naphthyridine. PMID- 26548993 TI - An efficient heterogeneous catalyst (CuO@ARF) for on-water C-S coupling reaction: an application to the synthesis of phenothiazine structural scaffold. AB - BACKGROUND: Aryl sulfides have significant importance from biological and pharmaceutical aspects. Transition metal-catalyzed carbon-sulfur cross-coupling reaction represents an important tool for the synthesis of sulfides. Among various transition metals, copper salts or oxides have found vast applicability. RESULTS: A simple procedure for the preparation of poly-ionic amberlite resins embedded with copper oxide nanoparticles (CuO NPs) (denoted as CuO@ARF) has been developed, characterized, and employed for the first time as a heterogeneous ligand-free catalyst for 'on-water' C-S cross-coupling reaction. The NPs of CuO with an average size (approximately 2.6 nm), as determined from high resolution transmission electron microscopy (HRTEM) images, are found to be a potentially active, chemoselective, and recyclable catalyst for the preparation of symmetrical and unsymmetrical aryl sulfides. Recycling of the catalyst was performed successfully for five consecutive runs, and apparently no leaching was observed in a hot filtration test. Excellent chemoselectivity between iodo- and bromo-arene has been exploited in step-wise C-S and C-N couplings to synthesize bioactive heterocyclic scaffold phenothiazine. CONCLUSIONS: An efficient method is established for the C-S cross-coupling reaction using heterogeneous catalyst CuO@ARF under ligand-free on-water condition. The catalyst is highly chemoselective among different aryl halides, which has been demonstrated in the synthesis heterocyclic scaffold phenothiazine. Furthermore, it is recyclable for five consecutive runs examined. Graphical abstract On-water C-S coupling using new heterogeneous nano-catalyst (CuO@ARF). PMID- 26548994 TI - Biophysical Characterization of the Nucleoside Diphosphate Kinase of Leishmania major and Effect of the P95S Mutation. AB - Nucleoside diphosphate kinases (NDK; EC 2.7.4.6) are enzymes required for maintaining intracellular levels of nucleosides triphosphates (NTP) through transfer the gamma-phosphoryl group from a NTP to a NDP. The enzyme is associated with several biological functions including prevention of host ATP-mediated cytolysis during pathogenic infections. Here we present the biophysical characterization of NDK from Leishmania major and the effect of a mutation on the protein structure in solution. The structural stability was analyzed since this secreted protein may act in different microenvironments at various stages of the parasite life cycle. LmNDK and P95S mutant were subjected to denaturation with pH and guanidine. Structural transitions were monitored by circular dichroism and intrinsic fluorescence tryptophan emission. Our results showed that the LmNDK is more structurally stable than other described NDKs and that the catalytically active P95S mutant in the Kpn loop presented a decrease in protein stability, indicating the importance of this proline for maintenance of the LmNDK structure. PMID- 26548995 TI - The Hexapeptide Repeated Segment LIAGY is a Hot Spot of Aggregation of the Pseudomonas syringae Ice Nucleation Protein. AB - Ice nucleation proteins (INPs) form oligomeric structures by self-assembly and aggregation. We looked for the presence of potential aggregating sequences inside the INP from Pseudomonas syringae by a computational approach with the AGGRESCAN, FOMDAMYLOID and TANGO softwares. A total of 38 hot spots of aggregation were predicted in the INP sequence: 7 localized in the Nterminal domain, 2 in the C terminal region, 28 in the highly repetitive central (HRC) region and 1 shared between the HRC and the Carboxyl-terminus regions of the protein. All the hot spots of aggregation identified in the HRC domain overlapped a 8-residue low fidelity repeat including a LIAGYrelated sequence. We confirmed the predictions by an experimental approach using synthetic peptides corresponding to different parts of the INP central sequence, absorbance spectroscopy and fluorescence spectroscopy in the presence of Congo red (CR) or Thioflavin T (ThT), respectively. Peptide 620-SFIIAGYG-627 predicted to aggregate by the three softwares induced an increase in fluorescence of ThT. Peptide 729-GFKSILTAGY-738 predicted to aggregate by AGGRESCAN and FOLDAMYLOID induced a shift in the maximum of absorbance of CR. Peptide 1124-SVLTAGA-1130 predicted to aggregate only by TANGO did not interfere with CR absorbance or ThT fluorescence. In conclusion, the use of three aggregation prediction algorithms and two biochemical assays showed that the hexapeptide repeated segment LIAGY, previously shown to form a hairpin loop may be involved in the aggregation of the P. syringae INP. PMID- 26548997 TI - From bench to bedside: Can the improvements in left ventricular assist device design mitigate adverse events and increase survival? AB - OBJECTIVE: In vitro tests demonstrated that the new cone-bearing configuration of the Jarvik 2000 (Jarvik Heart Inc, New York, NY) left ventricular assist device exhibits better hydraulic efficiency than the previous pin-bearing design. We investigated the long-term outcomes of patients who received the Jarvik 2000 left ventricular assist device, depending on bearing design. METHODS: A retrospective review of prospectively collected data from 18 centers included in the Italian Registry was performed. From May 2008 to September 2013, 99 patients with end stage heart failure were enrolled. Patients were divided into 2 groups according to their Jarvik 2000 suspending mechanism: Group pin included patients with pin bearings (May 2008 to June 2010), and group cone included patients with newer cone bearings (July 2010 to September 2013). The 2 groups did not differ significantly in terms of baseline characteristics. RESULTS: A total of 30 of 39 patients (group pin) and 46 of 60 patients (group cone) were discharged. During follow-up, 6 patients underwent transplantation, and in 1 patient the left ventricular assist device was explanted. The cumulative incidence competing risk of the entire cohort for noncardiovascular-related death was 28% (20%-40%); the cumulative incidence competing risk for cardiovascular-related death was 56% (42% 73%): 71% in group pin versus 26% in group cone (P = .034). The multivariate analyses confirmed that the pin-bearing design was a risk factor for cardiovascular death, along with Interagency Registry for Mechanically Assisted Circulatory Support class. Right ventricular failures and ischemic and hemorrhagic strokes were significantly higher in group pin. CONCLUSIONS: Patients with the new pump configuration showed a better freedom from cardiovascular death and lower incidence of fatal stroke and right ventricular failure. Further studies are needed to prove the favorable impact of pump-enhanced fluid dynamics on long-term results. PMID- 26548999 TI - How to build effective mentor-mentee relationships: Role of the mentee. PMID- 26548998 TI - Mechanical stress is associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot. AB - OBJECTIVE: Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. METHODS: Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. RESULTS: Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. CONCLUSIONS: Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings. PMID- 26549000 TI - The prognostic role of non-critical lactate levels for in-hospital survival time among ED patients with sepsis. AB - OBJECTIVE: This study describes emergency department (ED) sepsis patients with non-critical serum venous lactate (LAC) levels (LAC <4.0 mmol/L) who suffered in hospital mortality and examines LAC in relation to survival times. METHODS: An ED based retrospective cohort study accrued September 2010 to August 2014. Inclusion criteria were ED admission, LAC sampling, >2 systemic inflammatory response syndrome criteria with an infectious source (sepsis), and in-hospital mortality. Kaplan-Meier curves were used for survival estimates. An a priori sub-group analysis for patients with repeat LAC within 6 hours of initial sampling was undertaken. The primary outcome was time to in-hospital death evaluated using rank-sum tests and regression models. RESULTS: One hundred ninety-seven patients met inclusion criteria. Pulmonary infections were the most common (44%) and median LAC was 1.9 mmol/L (1.5, 2.5). Thirteen patients (7%) died within 24 hours and 79% by <=28 days. Median survival was 11 days (95% CI, 8.0-13). Sixty-two patients had repeat LAC sampling with 14 (23%) and 48 (77%) having decreasing increasing levels, respectively. No significant differences were observed in treatment requirements between the LAC subgroups. Among patients with decreasing LAC, median survival was 24 days (95% CI, 5-32). For patients with increasing LAC median survival was significantly shorter (7 days; 95% CI, 4-11, P = .04). Patients with increasing LAC had a non-significant trend toward reduced survival (HR = 1.6 95% CI, 0.90-3.0, P = .10). CONCLUSIONS: In septic ED patients experiencing in-hospital death, non-critical serum venous lactate may be utilized as a risk-stratifying tool for early mortality, while increasing LAC levels may identify those in danger of more rapid deterioration. PMID- 26549001 TI - Consumption of Alcohol Surrogates Among Alcohol-Dependent Women. AB - This is the first in-depth study of alcohol and surrogate drinking patterns, types, reasons, and correlates among alcohol-dependent women in Belarus. The structured interviews were performed in 2013 with 103 alcohol-dependent women admitted to a narcological clinic in Grodno, Belarus. The results suggest that at least 30.3% of alcohol-dependent women regularly consume samogon (moonshine) and 10.8% of women use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that samogon exceeds licensed vodka in quality is the main motive for its consumption. The results from the present study confirm that noncommercial alcohol use is common among alcohol-dependent women although its use may be underreported. These findings emphasize that the implementation of a comprehensive alcohol policy must take fully into account the consumption of alcohol from illicit sources. PMID- 26549002 TI - Pension Reform in China. AB - This article analyzes China's pension arrangement and notes that China has recently established a universal non-contributory pension plan covering urban non employed workers and all rural residents, combined with the pension plan covering urban employees already in place. Further, in the latest reform, China has discontinued the special pension plan for civil servants and integrated this privileged welfare class into the urban old-age pension insurance program. With these steps, China has achieved a degree of universalism and integration of its pension arrangement unprecedented in the non-Western world. Despite this radical pension transformation strategy, we argue that the current Chinese pension arrangement represents a case of "incomplete" universalism. First, its benefit level is low. Moreover, the benefit level varies from region to region. Finally, universalism in rural China has been undermined due to the existence of the "policy bundle." Additionally, we argue that the 2015 pension reform has created a situation in which the stratification of Chinese pension arrangements has been "flattened," even though it remains stratified to some extent. PMID- 26549004 TI - Elevated Cardiac Enzymes in Hypertrophic Cardiomyopathy Patients With Heart Failure - A 20-Year Prospective Follow-up Study. AB - BACKGROUND: To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling. METHODS AND RESULTS: Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB >=2.5%, n=33) and group L (CK-MB <2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P<0.0001), fractional shortening decreased (P<0.0004), and left atrial dimension increased (P<0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P<0.02) and left atrial dimension increased (P<0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H. CONCLUSIONS: Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF. PMID- 26549006 TI - [Haemorrhagic disease of the newborn after home delivery]. PMID- 26549005 TI - [Post-vaccinal herpes zoster: Value of the Tzank cytodiagnostic test]. PMID- 26549007 TI - Cryo-planing of frozen-hydrated samples using cryo triple ion gun milling (CryoTIGMTM). AB - Cryo-SEM is a high throughput technique for imaging biological ultrastructure in its most pristine state, i.e. without chemical fixation, embedding, or drying. Freeze fracture is routinely used to prepare internal surfaces for cryo-SEM imaging. However, the propagation of the fracture plane is highly dependent on sample properties, and the resulting surface frequently shows substantial topography, which can complicate image analysis and interpretation. We have developed a broad ion beam milling technique, called cryogenic triple ion gun milling (CryoTIGMTM ['kri-e-,tim]), for cryo-planing frozen-hydrated biological specimens. Comparing sample preparation by CryoTIGMTM and freeze fracture in three model systems, Baker's yeast, mouse liver tissue, and whole sea urchin embryos, we find that CryoTIGMTM yields very large (~700,000 MUm(2)) and smooth sections that present ultrastructural details at similar or better quality than freeze-fractured samples. A particular strength of CryoTIGMTM is the ability to section samples with hard-soft contrast such as brittle calcite (CaCO3) spicules in the sea urchin embryo. PMID- 26549008 TI - Eveningness and Its Associated Impairments in Remitted Bipolar Disorder. AB - Sleep-wake and circadian rhythm disturbances are common in remitted bipolar disorder. These disturbances include difficulty initiating and maintaining sleep, daytime sleepiness, sleep irregularity, and a circadian tendency toward eveningness. To date, few studies have examined the impact of eveningness on impairments in remitted bipolar disorder. Ninety-eight adults diagnosed with bipolar disorder I, II, or not otherwise specified were evaluated. Hierarchical linear regression analyses showed that eveningness was associated with greater sleep-wake disturbances, more unhealthy dietary habits, worse quality of life, more impaired interpersonal relationships, and more dysfunctional sleep-related cognitions and behaviors, controlling for age, gender, and years of education. Targeted intervention on dysfunctional sleep-related cognitions and behaviors may reverse eveningness and improve functioning in bipolar disorder. PMID- 26549009 TI - Rapid method of luxS and pfs gene inactivation in enterotoxigenic Escherichia coli and the effect on biofilm formation. AB - Rapid and efficient inactivation of a target gene in Escherichia coli chromosomes is required to investigate metabolic engineering. In the present study, a multiple gene inactivation approach was demonstrated in four strains of enterotoxigenic E. coli (ETEC), which are the predominant pathogenic bacteria causing piglet diarrhea, mediated by lambda Red and Xer recombination. The chromosomal genes, luxS and pfs were inactivated using the multiple gene inactivation approach in the wild-type strains of E. coli, K88, K99, 987P and F41. This indicated that dif sites may be reused to inactivate multiple chromosomal genes when no antibiotic-resistant selectable markers remain. Following inactivation of luxS and pfs, the ability of ETEC to produce the quorum sensing signal, and induce auto-inducer 2 activity and biofilm formation were significantly reduced. Furthermore, the multiple gene inactivation approach also exhibits a high recombination efficiency and follows a simple process. PMID- 26549010 TI - Daclatasvir for the treatment of chronic hepatitis C. AB - INTRODUCTION: Following more than 20 years of Interferon (IFN)-based treatment for hepatitis C virus (HCV), the understanding of viral life cycle led to the development of new antiviral drugs directly targeting HCV replication steps. Daclatasvir (DCV) is a potent inhibitor of non-structural NS5A HCV protein with pangenotypic activity and low-moderate barrier to resistance suitable for IFN free combination with other direct acting antivirals (DAAs). AREAS COVERED: The present review summarizes DCV key pharmacokinetic features and results from Phase II and III trials, discussing also NS5A resistance. Main literature articles have been identified through Pubmed and Medline search; moreover, abstracts from recent international meetings on liver disease have been scrutinized. EXPERT OPINION: DCV in combination with other DAAs has provided IFN-free regimens with increased efficacy and tolerability. However, suboptimal barrier to resistance and the rapid development of new second-generation NS5A inhibitors will probably make DCV a relatively short-lived drug. PMID- 26549011 TI - Relaxation damping in oscillating contacts. AB - If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect "relaxation damping". The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed. PMID- 26549012 TI - Experimental Spinal Stenosis in Cats: New Insight in Mechanisms of Hydrocephalus Development. AB - In our new experimental model of cervical stenosis without inflammation we have tested hypothesis that cranio-spinal communication impairment could lead to hydrocephalus development. Spinal and cranial cerebrospinal fluid (CSF) space separation was obtained with positioning of plastic semiring in epidural space at C2 level in cats. Brain ventricles planimetry, and CSF pressure recording in lateral ventricle (LV) and lumbar subarachnoid space (LSS) were performed in acute and subchronic experiments. In all experiments opening CSF pressures were normal. However, in acute experiments, an infusion of artificial CSF into the LV led to increase of CSF pressure and significant gradient pressure development between LV and LSS due to limited pressure transmission. After 3 or 6 weeks spinal cord atrophy was observed at the site of cervical stenosis, and pressure transmission from LV to LSS was improved as a consequence of spinal tissue atrophy. Planimetry of both the coronal brain slices and the ventricles' surface showed that control ventricular surface was 0.6 +/- 0.1% (n = 5), and 1.6 +/- 0.2% (n = 4) in animals with subchronic cervical stenosis (P < 0.002). These results support the mentioned hypothesis claiming that CSF volume cranio-spinal displacement impairment could start pathophysiological processes leading to development of hydrocephalus. PMID- 26549013 TI - The diverse oncogenic and tumor suppressor roles of salt-inducible kinase (SIK) in cancer. AB - INTRODUCTION: The salt-inducible kinases originally cloned in adrenal glands of high salt diet-fed rats, generally named as SIKs, are highly evolutionarily conserved serine/threonine protein kinases belonging to a family of AMP-activated protein kinase (AMPK). Overexpression of SIK2 and SIK3 is discovered in many tumors. Whereas, SIK1 expression was significantly lower in tumors than in normal tissues. AREAS COVERED: The main aim of our review is to introduce the signaling pathways as well as its mechanisms underlying their activity regulation, and especially the roles they play in cancer, which may shed light on the prospects of the cancer prevention and therapeutic targeting of SIKs in the future. EXPERT OPINION: It is conceivable that SIKs, mainly stimulated by ACTH, LKB1, TGF-beta, and autophosphorylation, play crucial roles in regulating multiple signal pathways in cancer cells and controlling a series of cellular processes including cell proliferation and cell apoptosis. More recent studies about SIKs are emerging, and their overexpression is found in a few specific types of cancers. However, correlations between SIKs and carcinogenesis remain to be fully elucidated. PMID- 26549014 TI - Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs. AB - Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using MicrominipigTM. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD induced dysfunction of cholesterol metabolism. PMID- 26549015 TI - Deciphering Supramolecular Structures with Protein-Protein Interaction Network Modeling. AB - Many biological molecules are assembled into supramolecules that are essential to perform complicated functions in the cell. However, experimental information about the structures of supramolecules is not sufficient at this point. We developed a method of predicting and modeling the structures of supramolecules in a biological network by combining structural data of the Protein Data Bank (PDB) and interaction data in IntAct databases. Templates for binary complexes in IntAct were extracted from PDB. Modeling was attempted by assembling binary complexes with superposed shared subunits. A total of 3,197 models were constructed, and 1,306 (41% of the total) contained at least one subunit absent from experimental structures. The models also suggested 970 (25% of the total) experimentally undetected subunit interfaces, and 41 human disease-related amino acid variants were mapped onto these model-suggested interfaces. The models demonstrated that protein-protein interaction network modeling is useful to fill the information gap between biological networks and structures. PMID- 26549016 TI - Catalytic Upgrading of 5-Hydroxymethylfurfural to Drop-in Biofuels by Solid Base and Bifunctional Metal-Acid Catalysts. AB - Design and synthesis of effective heterogeneous catalysts for the conversion of biomass intermediates into long chain hydrocarbon precursors and their subsequent deoxygenation to hydrocarbons is a viable strategy for upgrading lignocellulose into distillate range drop-in biofuels. Herein, we report a two-step process for upgrading 5-hydroxymethylfurfural (HMF) to C9 and C11 fuels with high yield and selectivity. The first step involves aldol condensation of HMF and acetone with a water tolerant solid base catalyst, zirconium carbonate (Zr(CO3 )x ), which gave 92 % C9 -aldol product with high selectivity at nearly 100 % HMF conversion. The as-synthesised Zr(CO3 )x was analysed by several analytical methods for elucidating its structural properties. Recyclability studies of Zr(CO3 )x revealed a negligible loss of its activity after five consecutive cycles over 120 h of operation. Isolated aldol product from the first step was hydrodeoxygenated with a bifunctional Pd/Zeolite-beta catalyst in ethanol, which showed quantitative conversion of the aldol product to n-nonane and 1-ethoxynonane with 40 and 56 % selectivity, respectively. 1-Ethoxynonane, a low oxygenate diesel range fuel, which we report for the first time in this paper, is believed to form through etherification of the hydroxymethyl group of the aldol product with ethanol followed by opening of the furan ring and hydrodeoxygenation of the ether intermediate. PMID- 26549017 TI - Adults' Detection of Deception in Children: Effect of Coaching and Age for Children's True and Fabricated Reports of Injuries. AB - A total of 1,074 undergraduates judged the truthfulness of children's interviews (from verbatim transcripts) about experiencing injuries serious enough to require hospital emergency room treatment. Ninety-six children (three age groups: 5-7, 8 10, and 11-14 years, 50% girls) were interviewed. At each age, 16 children told truthful accounts of actual injury experiences and 16 fabricated their reports, with half of each group coached by parents for the previous 4 days. Lies by 5- to 7-year-olds, whether coached or not, were detected at above-chance levels. In contrast, 8- to 10-year-olds' accounts that were coached, whether true or not, were more likely to be believed. For 11- to 14-year-olds, adults were less likely to accurately judge lies if they were coached. The believability of children aged 8 or above who were coached to lie is particularly disturbing in light of the finding that participants were more confident in the accuracy of their veracity decisions when judging coached reports. PMID- 26549018 TI - Multimodal super-resolution optical microscopy visualizes the close connection between membrane and the cytoskeleton in liver sinusoidal endothelial cell fenestrations. AB - Liver sinusoidal endothelial cells (LSECs) act as a filter between blood and the hepatocytes. LSECs are highly fenestrated cells; they contain transcellular pores with diameters between 50 to 200 nm. The small sizes of the fenestrae have so far prohibited any functional analysis with standard and advanced light microscopy techniques. Only the advent of super-resolution optical fluorescence microscopy now permits the recording of such small cellular structures. Here, we demonstrate the complementary use of two different super-resolution optical microscopy modalities, 3D structured illumination microscopy (3D-SIM) and single molecule localization microscopy in a common optical platform to obtain new insights into the association between the cytoskeleton and the plasma membrane that supports the formation of fenestrations. We applied 3D-SIM to multi-color stained LSECs to acquire highly resolved overviews of large sample areas. We then further increased the spatial resolution for imaging fenestrations by single molecule localization microscopy applied to select small locations of interest in the same sample on the same microscope setup. We optimized the use of fluorescent membrane stains for these imaging conditions. The combination of these techniques offers a unique opportunity to significantly improve studies of subcellular ultrastructures such as LSEC fenestrations. PMID- 26549019 TI - Solution-focused group therapy for common mental health problems: Outcome assessment in routine clinical practice. AB - OBJECTIVES: This study aimed to assess the effectiveness of solution-focused group therapy (SFGT) for psychological distress and mild to moderate depression in a routine clinical practice setting. DESIGN AND METHODS: A naturalistic pre/post-study involving 132 mental health service users was carried out. Clients received seven structured sessions of SFGT, and pre-therapy self-report scores (Spanish brief version of Beck Depression Inventory and Hospital Anxiety and Depression Scale) were compared with post-therapy scores. Additional data on effectiveness of intervention (discharges, clients returning for help and dropout rate) were analysed at 6, 12, and 24 months after initiating intervention and compared with a control sample (132 mental health service users, frequency matched by local health board, clinical diagnosis, and gender to the group intervention) receiving usual care (UC: Psychotropic medication and/or individual psychotherapy). RESULTS: Mean post-SFGT levels were significantly lower than mean pre-SFGT levels on each self-report measure in the SFGT sample. In addition, SFGT showed a significantly higher percentage of discharges and fewer clients returning for help than with UC. CONCLUSIONS: SFGT included in routine clinical practice may enhance the effectiveness of treatment in clients who suffer from depression and/or psychological distress. PRACTITIONER POINTS: Therapists could use SFGT as a brief and effective tool to deal with the most prevalent mental health problems at mental healthcare centres (MHCs) in Spain, without changing day-to-day clinical routines. SFGT might be effectively incorporated in routine clinical practice for helping people with psychological distress and depressive episodes of mild and moderate severity. This study should encourage systemic therapists and strategically oriented clinicians to continue delivering and offering outcome measures of solution-focused therapy. PMID- 26549020 TI - Do community hospice programmes reduce hospitalisation rate in patients with advanced chronic obstructive pulmonary disease? AB - BACKGROUND: Since Hinton first published his observations on the distress of patients dying on a medical ward in 1963, there has been increasing awareness of the palliative care needs in patients who have non malignant diseases. Patients with advanced chronic obstructive pulmonary disease (COPD) are known to have comparable symptom burden to lung cancer patients and are more likely receive invasive treatment at the end of life than patients with end stage lung cancer. They are also less likely to receive hospice services, and the benefit of such programmes in this key group of patients remain largely unknown, in particular what effect hospice programmes have on hospitalisation. AIMS: (i) To examine any effect of community hospice programmes on hospitalisation in patients with advanced COPD. (ii) To identify any association between utilisation of specific hospice services with hospitalisation. (iii) To describe key peri-mortem outcomes. METHODS: This was a retrospective study of consecutive patients with COPD admitted into community hospice programmes in the greater Wellington region, New Zealand between 1 October 2007 and 31 October 2013. RESULTS: A mean decrease of 2.375 (median decrease of 2; 95% confidence interval 1, 3) hospital admissions over a 12-month period was found after admission into hospice programme (P < 0.0005). CONCLUSION: Community hospice programmes may be associated with reduction in hospitalisation in patients with advanced COPD. PMID- 26549003 TI - Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. AB - BACKGROUND: The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. AIM: To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. METHODS: Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29 40). RESULTS: Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47 6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). CONCLUSION: Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men. PMID- 26549021 TI - Depletion of three combined THOC5 mRNA export protein target genes synergistically induces human hepatocellular carcinoma cell death. AB - Hepatocellular carcinoma (HCC) is a frequent form of cancer with a poor prognosis and with limited possibilities of medical intervention. It has been shown that over 100 putative driver genes are associated with multiple recurrently altered pathways in HCC, suggesting that multiple pathways will need to be inhibited for any therapeutic method. mRNA processing is regulated by a complex RNA-protein network that is essential for the maintenance of homeostasis. THOC5, a member of mRNA export complex, has a role in less than 1% of mRNA processing, and is required for cell growth and differentiation, but not for cell survival in normal fibroblasts, hepatocytes and macrophages. In this report, we show that 50% depletion of THOC5 in human HCC cell lines Huh7 and HepG2 induced apoptosis. Transcriptome analysis using THOC5-depleted cells revealed that 396 genes, such as transmembrane BAX inhibitor motif containing 4 (TMBIM4), transmembrane emp24 like trafficking protein 10 (Tmed10) and D-tyrosyl-tRNA deacylase 2 (Dtd2) genes were downregulated in both cell lines. The depletion of one of these THOC5 target genes in Huh7 or HepG2 did not significantly induce cell death, suggesting that these may be fine tuners for HCC cell survival. However, the depletion of a combination of these genes synergistically increased the number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive HCC. It must be noted that the depletion of these genes did not induce cell death in the hepatocyte cell line, THLE-2 cells. THOC5 expression was enhanced in 78% of cytological differentiation grading G2 and G3 tumor in primary HCC. Furthermore, the expression of a putative glycoprotein, Tmed10, is correlated to THOC5 expression level in primary HCCs, suggesting that this protein may be a novel biomarker for HCC. These data imply that the suppression of the multiple THOC5 target genes may represent a novel strategy for HCC therapy. PMID- 26549022 TI - Chronophin is a glial tumor modifier involved in the regulation of glioblastoma growth and invasiveness. AB - Glioblastoma is the most aggressive primary brain tumor in adults. Although the rapid recurrence of glioblastomas after treatment is a major clinical challenge, the relationships between tumor growth and intracerebral spread remain poorly understood. We have identified the cofilin phosphatase chronophin (gene name: pyridoxal phosphatase, PDXP) as a glial tumor modifier. Monoallelic PDXP loss was frequent in four independent human astrocytic tumor cohorts and increased with tumor grade. We found that aberrant PDXP promoter methylation can be a mechanism leading to further chronophin downregulation in glioblastomas, which correlated with shorter glioblastoma patient survival. Moreover, we observed an inverse association between chronophin protein expression and cofilin phosphorylation levels in glioma tissue samples. Chronophin-deficient glioblastoma cells showed elevated cofilin phosphorylation, an increase in polymerized actin, a higher directionality of cell migration, and elevated in vitro invasiveness. Tumor growth of chronophin-depleted glioblastoma cells xenografted into the immunodeficient mouse brain was strongly impaired. Our study suggests a mechanism whereby the genetic and epigenetic alterations of PDXP resulting in altered chronophin expression may regulate the interplay between glioma cell proliferation and invasion. PMID- 26549023 TI - The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin deficient tumors. AB - Merlin has broad tumor-suppressor functions as its mutations have been identified in multiple benign tumors and malignant cancers. In all schwannomas, the majority of meningiomas and 1/3 of ependymomas Merlin loss is causative. In neurofibromatosis type 2, a dominantly inherited tumor disease because of the loss of Merlin, patients suffer from multiple nervous system tumors and die on average around age 40. Chemotherapy is not effective and tumor localization and multiplicity make surgery and radiosurgery challenging and morbidity is often considerable. Thus, a new therapeutic approach is needed for these tumors. Using a primary human in vitro model for Merlin-deficient tumors, we report that the Ras/Raf/mitogen-activated protein, extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) scaffold, kinase suppressor of Ras 1 (KSR1), has a vital role in promoting schwannomas development. We show that KSR1 overexpression is involved in many pathological phenotypes caused by Merlin loss, namely multipolar morphology, enhanced cell-matrix adhesion, focal adhesion and, most importantly, increased proliferation and survival. Our data demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesion is more dependent on KSR1 than MEK1/2. Immunoprecipitation analysis reveals that KSR1 is a novel binding partner of Merlin, which suppresses KSR1's function by inhibiting the binding between KSR1 and c-Raf. Our proteomic analysis also demonstrates that KSR1 interacts with several Merlin downstream effectors, including E3 ubiquitin ligase CRL4(DCAF1). Further functional studies suggests that KSR1 and DCAF1 may co-operate to regulate schwannomas formation. Taken together, these findings suggest that KSR1 serves as a potential therapeutic target for Merlin-deficient tumors. PMID- 26549024 TI - RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress. AB - The DNA replication machinery invariably encounters obstacles that slow replication fork progression, and threaten to prevent complete replication and faithful segregation of sister chromatids. The resulting replication stress activates ATR, the major kinase involved in resolving impaired DNA replication. In addition, replication stress also activates the related kinase ATM, which is required to prevent mitotic segregation errors. However, the molecular mechanism of ATM activation by replication stress is not defined. Here, we show that monoubiquitinated Proliferating Cell Nuclear Antigen (PCNA), a marker of stalled replication forks, interacts with the ATM cofactor ATMIN via WRN-interacting protein 1 (WRNIP1). ATMIN, WRNIP1 and RAD18, the E3 ligase responsible for PCNA monoubiquitination, are specifically required for ATM signalling and 53BP1 focus formation induced by replication stress, not ionising radiation. Thus, WRNIP1 connects PCNA monoubiquitination with ATMIN/ATM to activate ATM signalling in response to replication stress and contribute to the maintenance of genomic stability. PMID- 26549025 TI - Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. AB - Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation and are associated with the development of cancers. To investigate the important role and mechanism of lncRNAs in the progression of gastric cancer, we screened lncRNAs in gastric cancer tissues and corresponding adjacent tissues, and assessed the effects on gastric cancer. Here, we report that BC032469, a novel lncRNA, expressed highly in gastric cancer tissues, and the upregulation was clinically associated with larger tumor size, poor differentiation and shorter survival of gastric cancer patients. Downregulation of BC032469 resulted in a significant inhibition of proliferation in vitro and in vivo. Mechanistically, BC032469 could directly bind to miR-1207-5p and effectively functioned as a sponge for miR-1207-5p to modulate the derepression of hTERT. Thus, BC032469 may function as a ceRNA to impair miR-1207-5p-dependent hTERT downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer. PMID- 26549026 TI - E2f3 in tumor macrophages promotes lung metastasis. AB - The Rb-E2F axis is an important pathway involved in cell-cycle control that is deregulated in a number of cancers. E2f transcription factors have distinct roles in the control of cell proliferation, cell survival and differentiation in a variety of tissues. We have previously shown that E2fs are important downstream targets of a CSF-1 signaling cascade involved in myeloid development. In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. Using the MMTV-Polyoma Middle T antigen (PyMT) mouse model of human ductal carcinoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenuates lung metastasis without affecting primary tumor growth. Histological analysis and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TAMs, but rather controls a novel gene expression signature associated with cytoskeleton rearrangements, cell migration and adhesion. This E2f3 TAM gene expression signature was sufficient to predict cancer recurrence and overall survival of estrogen receptor (ER)-positive breast cancer patients. Interestingly, we find that E2f3b but not E2f3a levels are elevated in TAMs from PyMT mammary glands relative to controls, suggesting a differential role for these isoforms in metastasis. In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influences the tumor microenvironment and tumor cell metastasis. PMID- 26549027 TI - Cytoplasmic PML promotes TGF-beta-associated epithelial-mesenchymal transition and invasion in prostate cancer. AB - Epithelial-mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-beta signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-beta signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-beta canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-beta signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit. PMID- 26549028 TI - Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b. AB - Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of diseases, including many tumors. However, the functional roles of these transcripts and mechanisms responsible for their deregulation in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly understood. In this study, we discovered that lncRNA MIR31HG is markedly upregulated in PDAC. Knockdown of MIR31HG significantly suppressed PDAC cell growth, induced apoptosis and G1/S arrest, and inhibited invasion, whereas enhanced expression of MIR31HG had the opposite effects. Online database analysis tools showed that miR-193b could target MIR31HG and we found an inverse correlation between MIR31HG and miR-193b in PDAC specimens. Inhibition of miR-193b expression significantly upregulated the MIR31HG level, while overexpression of miR-193b suppressed MIR31HG's expression and function, suggesting that MIR31HG is negatively regulated by miR 193b. Moreover, using luciferase reporter and RIP assays, we provide evidence that miR-193b directly targeted MIR31HG by binding to two microRNA binding sites in the MIR31HG sequence. On the other hand, MIR31HG may act as an endogenous 'sponge' by competing for miR-193b binding to regulate the miRNA targets. Collectively, these results demonstrate that MIR31HG functions as an oncogenic lncRNA that promotes tumor progression, and miR-193b targets not only protein coding genes but also the lncRNA, MIR31HG. PMID- 26549029 TI - CTCF cooperates with noncoding RNA MYCNOS to promote neuroblastoma progression through facilitating MYCN expression. AB - Previous studies have indicated the important roles of MYCN in tumorigenesis and progression of neuroblastoma (NB), the most common extracranial solid tumor derived from neural crest in childhood. However, the regulatory mechanisms of MYCN expression in NB still remain largely unknown. In this study, through mining public microarray databases and analyzing the cis-regulatory elements and chromatin immunoprecipitation data sets, we identified CCCTC-binding factor (CTCF) as a crucial transcription factor facilitating the MYCN expression in NB. RNA immunoprecipitation, RNA electrophoretic mobility shift assay, RNA pull down and in vitro binding assay indicated the physical interaction between CTCF and MYCN opposite strand (MYCNOS), a natural noncoding RNA surrounding the MYNC promoter. Gain- and loss-of-function studies revealed that MYCNOS facilitated the recruitment of CTCF to its binding sites within the MYCN promoter to induce chromatin remodeling, resulting in enhanced MYCN levels and altered downstream gene expression, in cultured NB cell lines. CTCF cooperated with MYCNOS to suppress the differentiation and promote the growth, invasion and metastasis of NB cells in vitro and in vivo. In clinical NB tissues and cell lines, CTCF and MYCNOS were upregulated and positively correlated with MYCN expression. CTCF was an independent prognostic factor for unfavorable outcome of NB, and patients with high MYCNOS expression had lower survival probability. Taken together, these results demonstrate that CTCF cooperates with noncoding RNA MYCNOS to exhibit oncogenic activity that affects the aggressiveness and progression of NB through transcriptional upregulation of MYCN. PMID- 26549030 TI - Hepatitis C virus core protein interacts with Snail and histone deacetylases to promote the metastasis of hepatocellular carcinoma. AB - Downregulation of E-cadherin by the transcriptional repressor Snail is associated with acquisition of metastatic potential. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, it is unclear whether Snail is involved in HCV core-induced dysregulation of E-cadherin. Herein, we investigated the mechanism by which HCV core induces E-cadherin repression and the role of Snail in HCV core-mediated invasiveness and metastasis. We found that HCV infection, especially HCV core expression, effectively induced the epithelial mesenchymal transition (EMT) in hepatoma cells by repressing E-cadherin. HCV core interacted with Snail and enhanced its binding to the E-box in the promoter region of E-cadherin, leading to decreased E-cadherin promoter activity. We found that HCV core, Snail, and the histone deacetylases HDAC1/HDAC2 formed a co repressor complex at the E-cadherin promoter. Moreover, HCV core was shown to stabilize Snail through activation of the PI3K/Akt/GSK3beta pathway. Silencing Snail expression restored E-cadherin expression and inhibited HCV core-promoted tumor growth and distant lung metastasis in vivo. Collectively, these results demonstrated that HCV core induced EMT by interacting with the transcriptional repressor complex Snail/HDACs at the E-cadherin promoter, which led to E-cadherin repression and increased invasiveness of hepatoma cells. These findings increase understanding of factors regulating metastasis in hepatoma and may ultimately lead to the development of novel treatment strategies for HCV-associated hepatocellular carcinoma. PMID- 26549031 TI - Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high grade serous ovarian cancer. AB - Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (gammaH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of gammaH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of ovarian cancer by aiding the accumulation of DNA-DSBs in the fallopian tubal epithelium. PMID- 26549032 TI - RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines. AB - Ras GTPases are activated by RasGEFs and inactivated by RasGAPs, which stimulate the hydrolysis of RasGTP to inactive RasGDP. GTPase-impairing somatic mutations in RAS genes, such as KRAS(G12D), are among the most common oncogenic events in metastatic cancer. A different type of cancer Ras signal, driven by overexpression of the RasGEF RasGRP1 (Ras guanine nucleotide-releasing protein 1), was recently implicated in pediatric T-cell acute lymphoblastic leukemia (T ALL) patients and murine models, in which RasGRP1 T-ALLs expand in response to treatment with interleukins (ILs) 2, 7 and 9. Here, we demonstrate that IL-2/7/9 stimulation activates Erk and Akt pathways downstream of Ras in RasGRP1 T-ALL but not in normal thymocytes. In normal lymphocytes, RasGRP1 is recruited to the membrane by diacylglycerol (DAG) in a phospholipase C-gamma (PLCgamma)-dependent manner. Surprisingly, we find that leukemic RasGRP1-triggered Ras-Akt signals do not depend on acute activation of PLCgamma to generate DAG but rely on baseline DAG levels instead. In agreement, using three distinct assays that measure different aspects of the RasGTP/GDP cycle, we established that overexpression of RasGRP1 in T-ALLs results in a constitutively high GTP-loading rate of Ras, which is constantly counterbalanced by hydrolysis of RasGTP. KRAS(G12D) T-ALLs do not show constitutive GTP loading of Ras. Thus, we reveal an entirely novel type of leukemogenic Ras signals that is based on a RasGRP1-driven increased in flux through the RasGTP/GDP cycle, which is mechanistically very different from KRAS(G12D) signals. Our studies highlight the dynamic balance between RasGEF and RasGAP in these T-ALLs and put forth a new model in which IL-2/7/9 decrease RasGAP activity. PMID- 26549033 TI - DNA methylation reactivates GAD1 expression in cancer by preventing CTCF-mediated polycomb repressive complex 2 recruitment. AB - Levels of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase 1 (GAD1), the enzyme that synthesizes GABA, are significantly increased in neoplastic tissues. However, the mechanism underlying this increase remains elusive. Instead of silencing gene transcription, we showed that the GAD1 promoter was hypermethylated in both colon and liver cancer cells, leading to the production of high levels of GAD1. GAD1 is a target gene that is silenced by H3K27me3. The key locus responsible for GAD1 reactivation was mapped to a DNA methylation-sensitive CTCF-binding site (CTCF-BS3) within the third intron of GAD1. Chromosome configuration capture (3C) analysis indicated that an intrachromosomal loop was formed by CTCF self-dimerisation in normal cells (CTCF binds to both unmethylated CTCF-BS3 and CTCF-BS2). The CTCF dimer then interacted with suppressor of zeste 12 homologue (SUZ12), which is a domain of Polycomb repressive complex 2 (PRC2), promoting the methylation of H3K27 and the silencing of GAD1 expression. This silencing was shown to be inhibited by DNA methylation in cancer cells. These findings strongly suggest that GAD1 is reactivated by DNA methylation, which provided a model for DNA methylation and the active orchestration of oncogenic gene expression by CTCF in cancer cells. PMID- 26549035 TI - Angiotensin receptor antagonist treatment, melanoma incidence and ethnicity. PMID- 26549034 TI - Co-active receptor tyrosine kinases mitigate the effect of FGFR inhibitors in FGFR1-amplified lung cancers with low FGFR1 protein expression. AB - Targeted therapies are effective in subsets of lung cancers with EGFR mutations and anaplastic lymphoma kinase (ALK) translocations. Large-scale genomics have recently expanded the lung cancer landscape with FGFR1 amplification found in 10 20% of squamous cell carcinomas (SCCs). However, the response rates have been low for biomarker-directed fibroblast growth factor receptor (FGFR) inhibitor therapy in SCC, which contrasts to the relatively high rates of response seen in EGFR mutant and ALK-translocated lung cancers treated with epidermal growth factor receptor (EGFR) inhibitors and ALK inhibitors, respectively. In order to better understand the low response rates of FGFR1-amplified lung cancers to FGFR inhibitors, relationships between gene copy number, mRNA expression and protein expression of FGFR1 were assessed in cell lines, tumor specimens and data from The Cancer Genome Atlas. The importance of these factors for the sensitivity to FGFR inhibitors was determined by analyzing drug screen data and conducting in vitro and in vivo experiments. We report that there was a discrepancy between FGFR1 amplification level and FGFR1 protein expression in a number of these cell lines, and the cancers with unexpectedly low FGFR1 expression were uniformly resistant to the different FGFR inhibitors. Further interrogation of the receptor tyrosine kinase activity in these discordant cell lines revealed co-activation of HER2 and platelet-derived growth factor receptor-alpha (PDGFRalpha) caused by gene amplification or ligand overexpression maintained phosphoinositide 3-kinase (PI3K) and MEK/ERK signaling even in the presence of FGFR inhibitor. Accordingly, co-inhibition of FGFR1 and HER2 or PDGFRalpha led to enhanced drug responses. In contrast, FGFR1-amplified high FGFR1 protein-expressing lung cancers are sensitive to FGFR inhibitor monotherapy by downregulating ERK signaling. Addition of a PI3K inhibitor to these high FGFR1 protein-expressing cancers further sensitized them to FGFR inhibitor. These data reveal that biomarker-directed trials for FGFR1-amplified SCC require assessment of FGFR1 protein expression and uncover novel therapeutic strategies for FGFR1-amplified SCC with low FGFR1 protein expression. PMID- 26549036 TI - Multivariate optimization of process parameters in the synthesis of calcined Ca Al (NO3) LDH for defluoridation using 3(3) factorial, central composite and Box Behnken design. AB - Response surface methodology was applied for the first time in the optimization of the preparation of layered double hydroxide (LDH) for defluoridation. The influence of three vital process parameters (viz. pH, molar ratio and calcination temperature) in the synthesis of the adsorbent 'Calcined Ca-Al (NO3) LDH' was thoroughly examined to maximize its fluoride scavenging potential. The process parameters were optimized using the 3(3) factorial, face centered central composite and Box-Behnken designs and a comparative assessment of the methods was conducted. The maximum fluoride removal efficiency was achieved at a calcination temperature of approximately 500oC; however, the efficiency decreased with increasing pH and molar ratio. The outcome of the comparative assessment clearly delineates the case specific nature of the models. A better predictability over the entire experimental domain was obtained with the 3(3) factorial method, whereas the Box-Behnken design was found to be the most efficient model with lesser number of experimental runs. The desirability function technique was performed for optimizing the response, wherein face centered central composite design exhibited a maximum desirability. The calcined Ca-Al (NO3) LDH, synthesized under the optimum conditions, demonstrated the removal efficiencies of 95% and 99% for the doses of 3 g L(-1) and 5 g L(-1), respectively. PMID- 26549037 TI - Evidence for an essential role of intradimer interaction in catalytic function of carnosine dipeptidase II using electrospray-ionization mass spectrometry. AB - Carnosine dipeptidase II (CN2/CNDP2) is an M20 family metallopeptidase that hydrolyses various dipeptides including beta-alanyl-L-histidine (carnosine). Crystallographic analysis showed that CN2 monomer is composed of one catalytic and one dimerization domains, and likely to form homodimer. In this crystal, H228 residue of the dimerization domain interacts with the substrate analogue bestatin on the active site of the dimer counterpart, indicating that H228 is involved in enzymatic reaction. In the present study, the role of intradimer interaction of CN2 in its catalytic activity was investigated using electrospray-ionization time of-flight mass spectrometry (ESI-TOF MS). First, a dimer interface mutant I319K was prepared and shown to be present as a folded monomer in solution as examined by using ESI-TOF MS. Since the mutant was inactive, it was suggested that dimer formation is essential to its enzymatic activity. Next, we prepared H228A and D132A mutant proteins with different N-terminal extended sequences, which enabled us to monitor dimer exchange reaction by ESI-TOF MS. The D132A mutant is a metal ligand mutant and also inactive. But the activity was partially recovered time dependently when H228A and D132A mutant proteins were incubated together. In parallel, H228A/D132A heterodimer was formed as detected by ESI-TOF MS, indicating that interaction of a catalytic center with H228 residue of the other subunit is essential to the enzymatic reaction. These results provide evidence showing that intradimer interaction of H228 with the reaction center of the dimer counterpart is essential to the enzymatic activity of CN2. PMID- 26549038 TI - Hyaluronan/Hyaladherins - a Promising Axis for Targeted Drug Delivery in Cancer. AB - BACKGROUND: Hyaluronan (HA), a glycosaminoglycan, is a key extracellular matrix (ECM) component, and has been established to contribute to fibrotic, angiogenic, inflammatory as well as processes supporting cancer development. The changes in HA deposition in different tumors have been widely studied. Indeed, a multitude of reports demonstrate that HA expression is increased in different neoplasmatic tissues including lung, colon, prostate and breast cancer. The aims of this paper are to critically and in depth discuss aspects of HA metabolism in cancer and recent developments of its utilization in cancer therapy. METHODS: Up to date research and online content are reviewed. RESULTS: The cellular roles of HA are perpetrated through molecular interactions with HA-binding proteins, called hyaladherins, including CD44 receptor as well as receptor for hyaluronan-mediated motility (RHAMM). HA binding can be followed by receptor-mediated endocytosis. Importantly, hyaladherins show an altered expression in tumor tissues. Indeed, post-translational alterations in CD44 structure have been suggested to regulate the equilibrium between the "inactive" low affinity state and the "active" high affinity state of the HA binding capacity. In this concept HA fragments can be utilized as specific targeting ligands for efficient and safe drug delivery in cancer. CONCLUSION: HA-drug bioconjugates and nanoparticles have emerged as a promising platform for drug delivery during cancer treatment as demonstrated in various pre-clinical studies. Recent developments from clinical trials indicate that the utilization of specific HA-drug bioconjugates might be approved for the medical practice in the nearest future. PMID- 26549039 TI - Co-Delivery of Atorvastatin Nanocrystals in PLGA based in situ Gel for Anti Hyperlipidemic Efficacy. AB - The objective was to develop chitosan atorvastatin (ATR) nanocrystals loaded into Poly (lactic-co-glycolic) acid (PLGA) injectable in situ gel (ISG) system that can minimize initial drug burst and enhance hypolipidemic effect. ATR nanocrystals were successfully characterized for size, morphology, crystallinity and drug-excipients interaction. The effects of varied polymer concentration and gelling solvents were evaluated for initial burst release and in vivo efficacy. Short term stability study was also conducted for the promising formulation. Nanocrystals of size 254 nm were prepared using low molecular weight chitosan and were of smooth surface with multiple scaffolds like structures. X-ray powder diffraction revealed the crystalline structure of the prepared nanocrystals while no drug-excipients interactions were observed. Addition of nanocrystals did not significantly alter gelation property of the ISG system that showed acceptable syringeability. The promising ISG formulation was achieved with 45% PLGA in N methyl pyrrolidone: benzyl benzoate (1:3). In-vitro dissolution study illustrated lower initial ATR burst and prolonged drug release from nanocrystal based ISG when compared to plain ATR ISG. The pharmacokinetic and hypolipidemic biochemical parameters were comparable in the two formulations. The promising formulation exhibited minimum drug degradation at 4 °C and so could be considered as an ideal ISG delivery system. PMID- 26549040 TI - Reversal of Oxidative Stress in Neural Cells by an Injectable Curcumin/Thermosensitive Hydrogel. AB - Curcumin as an antioxidative agent which has been widely used medicinally in India and China. However, rapid metabolism coupled with the instability of curcumin under physiological conditions has greatly limited its applications in vivo. In the present study, a thermosensitive hydrogel with high payload of curcumin was developed by using a co-precipitation method, and its reversion of oxidative stress in Neuro-2a cells was investigated. With an increase in drug loading capacity, the solgel transition temperature of the thermosensitive hydrogel decreased accordingly. The stability of curcumin in phosphate-buffered saline (PBS; pH=7.4) was greatly improved by encapsulation in the thermosensitive hydrogel, as indicated by an in vitro degradation test. An in vitro release study showed that the encapsulated curcumin was rapidly released from the hydrogel within 6 h. A curcumin/F-127 aqueous solution under the threshold concentration of 4MUg/mL was non-toxic against Neuro-2a cells after 24-h incubation. A MitoSOX assay indicated that the developed curcumin formulation could attenuate the oxidative damage induced by H2O2 as compared to that of the H2O2 group. All these results suggested that the developed curcumin/thermosensitive hydrogel might have great potential application in the reversion of oxidative stress after traumatic brain injury. PMID- 26549041 TI - The Theory of Value-Based Payment Incentives and Their Application to Health Care. AB - OBJECTIVES: To present the implications of agency theory in microeconomics, augmented by behavioral economics, for different methods of value-based payment in health care; and to derive a set of future research questions and policy recommendations based on that conceptual analysis. DATA SOURCES: Original literature of agency theory, and secondarily behavioral economics, combined with applied research and empirical evidence on the application of those principles to value-based payment. STUDY DESIGN: Conceptual analysis and targeted review of theoretical research and empirical literature relevant to value-based payment in health care. PRINCIPAL FINDINGS: Agency theory and secondarily behavioral economics have powerful implications for design of value-based payment in health care. To achieve improved value-better patient experience, clinical quality, health outcomes, and lower costs of care-high-powered incentives should directly target improved care processes, enhanced patient experience, and create achievable benchmarks for improved outcomes. Differing forms of value-based payment (e.g., shared savings and risk, reference pricing, capitation, and bundled payment), coupled with adjunct incentives for quality and efficiency, can be tailored to different market conditions and organizational settings. CONCLUSIONS: Payment contracts that are "incentive compatible"-which directly encourage better care and reduced cost, mitigate gaming, and selectively induce clinically efficient providers to participate-will focus differentially on evidence-based care processes, will right-size and structure incentives to avoid crowd-out of providers' intrinsic motivation, and will align patient incentives with value. Future research should address the details of putting these and related principles into practice; further, by deploying these insights in payment design, policy makers will improve health care value for patients and purchasers. PMID- 26549042 TI - Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa. AB - Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)-positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV-negative and 15 HIV-positive) and 20 healthy controls were exposed to X-rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients. PMID- 26549043 TI - Recurring flood distribution patterns related to short-term Holocene climatic variability. AB - Millennial- and multi-centennial scale climate variability during the Holocene has been well documented, but its impact on the distribution and timing of extreme river floods has yet to be established. Here we present a meta-analysis of more than 2000 radiometrically dated flood units to reconstruct centennial scale Holocene flood episodes in Europe and North Africa. Our data analysis shows a general increase in flood frequency after 5000 cal. yr BP consistent with a weakening in zonal circulation over the second half of the Holocene, and with an increase in winter insolation. Multi-centennial length phases of flooding in UK and central Europe correspond with periods of minimum solar irradiance, with a clear trend of increasing flood frequency over the last 1000 years. Western Mediterranean regions show synchrony of flood episodes associated with negative phases of the North Atlantic Oscillation that are out-of-phase with those evident within the eastern Mediterranean. This long-term flood record reveals complex but geographically highly interconnected climate-flood relationships, and provides a new framework to understand likely future spatial changes of flood frequency. PMID- 26549044 TI - Clicking Hydrazine and Aldehyde: The Way to Labeling of Viruses with Quantum Dots. AB - Real-time tracking of fluorophore-tagged viruses in living cells can help uncover virus infection mechanisms. Certainly, the indispensable prerequisite for virus tracking is to label viruses with some bright and photostable beacons such as quantum dots (QDs) via an appropriate labeling strategy. Herein, we devise a convenient hydrazine-aldehyde based strategy to label viruses with QDs through the conjugation of 4-formylbenzoate (4FB) modified QDs to 6-hydrazinonicotinate acetone hydrazone (HyNic) modified viruses under mild conditions. On the basis of this strategy, viruses can be successfully labeled with QDs with high selectivity, stable conjugation, good reproducibility, high labeling efficiency of 92-93% and maximum retention of both fluorescence properties of QDs and infectivity of viruses, which is very meaningful to tracking and statistical analysis of virus infection processes. By further comparing with the most widely used labeling strategy based on the Biotin-SA system, this new strategy has advantages of both high labeling efficiency and good retention of virus infectivity, thus offering a promising alternative for virus-labeling. Moreover, due to the ubiquitous presence of exposed amino groups on the surface of various viruses, this selective, efficient, reproducible and biofriendly strategy should have good universality for labeling both enveloped and nonenveloped viruses. PMID- 26549045 TI - Rhodium-Catalyzed Intramolecular C-H Bond Activation with Triazoles: Preparation of Stereodefined Pyrrolidines and Other Related Cyclic Compounds. AB - On treatment of triazoles having an N-sulfonyl-protected benzylamine moiety with [Rh2 (C7 H15 CO2 )4 ], intramolecular C-H bond insertion takes place at the benzylic position to give cis-N-sulfonyl-2-aryl-3 [(sulfonylimino)methyl]pyrrolidines in good yields and with highly stereoselectivities. Analogously, the similar treatment of triazoles having an ether or even an alkyl moiety affords 2-alkyl- or 2-aryl-3 [(sulfonylimino)methyl]tetrahydrofurans or a 2-alkyl-3 [(sulfonylimino)methyl]cyclopentane in good yields. PMID- 26549046 TI - Factors affecting self-regulated learning in medical students: a qualitative study. AB - INTRODUCTION: Clinical courses are required of all medical students and means that they must develop the key skill of self-regulation during learning. The ability to self-regulate learning strategies is affected by different factors. This study determined the views of medical students on the factors affecting self regulated learning (SRL). METHOD: This study uses a qualitative approach and the content analysis method. Nineteen medical students in their fourth, fifth, and sixth years of study at Isfahan University of Medical Science participated in semi-structured, in-depth interviews. The students were selected using purposive sampling based on their overall grade point average (GPA). RESULTS: Five main themes were found to affect SRL. These themes included family with the two subthemes of family supervisory and supportive roles; peers with the two subthemes of facilitating and inhibiting roles; instructors with the two subthemes of personal and educational instructor's characteristics; educational environment with the two subthemes of facilitator and inhibitor roles; and student with the two subthemes of facilitating and inhibiting personal factors. CONCLUSION: The outcomes of student understanding of the factors affecting self regulation indicate that facilitating factors should be used on an individual basis to reduce the effect of inhibiting factors to improve self-regulation in students. PMID- 26549047 TI - Recruitment of rural healthcare professionals for live continuing education. AB - INTRODUCTION: The availability of rural healthcare is a growing concern in the United States as fewer healthcare providers choose to work in rural areas. Accessing quality continuing education (CE) for rural healthcare practitioners (HCPs) remains a challenge and may pose a barrier to quality care. METHODS: To maximize attendance at a live, in-person, free CE program focusing on geriatric medication and issues specifically targeted to HCPs in rural areas, two methods were implemented sequentially. The first method used formal advertising implemented by a professional marketing service to promote CE events. The second method enlisted local healthcare organizations and physician groups to promote the CE event to their employees. Cost per attendee was calculated for comparison. RESULTS: Professional marketing services recruited 31 HCPs (March 2011) and resulted in a per-participant recruitment cost of US$428.62. Local healthcare organizations and physician groups' marketing recruited 48 HCPs (July-August 2011) and resulted in a per-participant recruitment cost of US$55.19. DISCUSSION: Providing free CE coordinated through local healthcare organizations and physician groups was the most cost-effective method of recruiting rural HCPs for CE. Formal advertising added cost without increasing the number of participants per event. Although this is the first study of the cost-effectiveness of recruitment methods targeting HCPs in rural areas, results are consistent with research on cost-effectiveness of outreach to rural lay community members. PMID- 26549048 TI - Hyperproduction of beta-Glucanase Exg1 Promotes the Bioconversion of Mogrosides in Saccharomyces cerevisiae Mutants Defective in Mannoprotein Deposition. AB - Bacteria and fungi can secrete extracellular enzymes to convert macromolecules into smaller units. Hyperproduction of extracellular enzymes is often associated with alterations in cell wall structure in fungi. Recently, we identified that Saccharomyces cerevisiae kre6Delta mutants can efficiently convert mogroside V into mogroside III E, which has antidiabetic properties. However, the underlying efficient bioconversion mechanism is unclear. In the present study, the mogroside (MG) bioconversion properties of several cell wall structure defective mutants were analyzed. We also compared the cell walls of these mutants by transmission electron microscopy, a zymolyase sensitivity test, and a mannoprotein release assay. We found zymolyase-sensitive mutants (including kre1Delta, las21Delta, gas1Delta, and kre6Delta), with defects in mannoprotein deposition, exhibit efficient MG conversion and excessive leakage of Exg1; such defects were not observed in wild-type cells, or mutants with abnormal levels of glucans in the cell wall. Thus, yeast mutants defective in mannoprotein deposition may be employed to convert glycosylated bioactive compounds. PMID- 26549050 TI - Competitive electron transfer in a novel, broad-band capturing, subphthalocyanine AzaBODIPY-C60 supramolecular triad. AB - A V-configured subphthalocyanine-azaBODIPY-C60 supramolecular triad has been newly synthesized, and sequential energy and electron transfer leading to the formation of charge separated states, useful properties relevant for solar energy harvesting and building optoelectronic devices, is reported. PMID- 26549049 TI - GBA-associated parkinsonism and dementia: beyond alpha-synucleinopathies? AB - BACKGROUND AND PURPOSE: To date the role of GBA mutations beyond alpha synucleinopathies in the parkinsonism-dementia spectrum is still unclear. The aim of the study was to screen for GBA mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD). METHODS: In all, 303 patients with a clinical diagnosis of PSP (n = 157), CBS (n = 39), PPA (n = 35) and bvFTD (n = 72) and 587 neurologically healthy controls were screened for the most common GBA mutations. RESULTS: GBA mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP (n = 1), probable CBS (n = 2) and PPA (n = 1, with concomitant C9orf72 expansion). Overall the prevalence of GBA mutations was low in non-alpha-synucleinopathies but significantly higher in the CBS subgroup compared to controls. CONCLUSION: Although numbers are small, our findings indicate that the clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying alpha synucleinopathies. This may be of relevance, once causal therapeutic strategies for GBA-associated neurodegenerative disease are developed. PMID- 26549051 TI - Rapid bladder cancer cell detection from clinical urine samples using an ultra thin silicone membrane. AB - Early detection of initial onset, as well as recurrence, of cancer is paramount for improved patient prognosis and human health. Cancer screening is enhanced by rapid differentiation of cancerous from non-cancerous cells which employs the inherent differences in biophysical properties. Our preliminary testing demonstrates that cell-line derived bladder cancer cells deform our <30 nm silicone membrane within an hour and induce visually distinct wrinkle patterns while cell-line derived non-cancerous cells fail to induce these wrinkle patterns. Herein, we report a platform for the rapid detection of cancerous cells from human clinical urine samples. We performed a blinded study with cells extracted from the urine of human patients suspected to have bladder cancer alongside healthy controls. Wrinkle patterns were induced specifically by the five cancer patient samples within 12 hours and not by the healthy controls. These results were independently validated by the standard diagnostic techniques cystoscopy and cytology. Thus, our ultra-thin membrane approach for cancer diagnosis appears as accurate as standard diagnostic methods while vastly more rapid, less invasive, and requiring limited expertise. PMID- 26549052 TI - Prediction of spin-orbital coupling effects on the electronic structure of two dimensional van der Waals heterostructures. AB - We report a first-principles study on the electronic structure of van der Waals (vdW) heterostructures consisting of two dimensional (2D) materials. Herewith, we focus on the effects of spin-orbital coupling (SOC) and vdW forces. It is found that all 2D vdW heterostructures can preserve the electronic structure of the isolated 2D materials in the heterostructures. The 2D vdW h-BN/G and h-BN/BP heterostructures show the n-type Schottky barriers. The MoS2/G heterostructures show the p-type doping and a strong spin splitting due to SOC, which are the important features that provide a promising future for the application in electronics, optoelectronics and spin-filter devices. PMID- 26549054 TI - Hierarchically Structured Nanomaterials for Electrochemical Energy Conversion. AB - Hierarchical nanomaterials are highly suitable as electrocatalysts and electrocatalyst supports in electrochemical energy conversion devices. The intrinsic kinetics of an electrocatalyst are associated with the nanostructure of the active phase and the support, while the overall properties are also affected by the mesostructure. Therefore, both structures need to be controlled. A comparative state-of-the-art review of catalysts and supports is provided along with detailed synthesis methods. To further improve the design of these hierarchical nanomaterials, in-depth research on the effect of materials architecture on reaction and transport kinetics is necessary. Inspiration can be derived from nature, which is full of very effective hierarchical structures. Developing fundamental understanding of how desired properties of biological systems are related to their hierarchical architecture can guide the development of novel catalytic nanomaterials and nature-inspired electrochemical devices. PMID- 26549053 TI - Current and advancing treatments for metastatic colorectal cancer. AB - INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Despite the introduction of several new drugs targeting the vascular endothelial growth factor or epidermal growth factor receptor (EGFR) signaling pathways, survival and disease control in metastatic CRC remains poor. AREAS COVERED: Chemotherapy based on fluoropyrimidines and irinotecan or oxaliplatin has been the cornerstone of CRC standard of care for several decades. Optimal regimens are selected according to toxicity profiles and patient characteristics. The addition of targeted drugs inhibiting angiogenesis, notably bevacizumab, aflibercept and ramucirumab, has improved chemotherapy outcomes in metastatic CRC. Anti-EGFR agents, cetuximab and panitumumab, in combination with chemotherapy have also improved survival in patients with wild-type RAS tumors. In the refractory setting, there are emerging drugs such as regorafenib or TAS 102 that also have demonstrated impact on outcomes. EXPERT OPINION: Drugs targeting signaling pathways involved in tumorigenesis improve patient outcomes over chemotherapy alone. Determining the most suitable combination and sequence should be carefully selected, with studies yet to provide a definitive solution to this unknown. Molecular mechanisms of colorectal cancer are at the forefront of research. Knowledge in this domain will help overcome resistance to therapies and introduce new drugs in the personalized CRC therapeutic scenario. PMID- 26549055 TI - Informatics View on the Challenges of Identifying Missing Proteins from Shotgun Proteomics. AB - Protein experiment evidence at protein level from mass spectrometry and antibody experiments are essential to characterize the human proteome. neXtProt (2014-09 release) reported 20 055 human proteins, including 16 491 proteins identified at protein level and 3564 proteins unidentified. Excluding 616 proteins at uncertain level, 2948 proteins were regarded as missing proteins. Missing proteins were unidentified partially due to MS limitations and intrinsic properties of proteins, for example, only appearing in specific diseases or tissues. Despite such reasons, it is desirable to explore issues affecting validation of missing proteins from an "ideal" shotgun analysis of human proteome. We thus performed in silico digestions on the human proteins to generate all in silico fully digested peptides. With these presumed peptides, we investigated the identification of proteins without any unique peptide, the effect of sequence variants on protein identification, difficulties in identifying olfactory receptors, and highly similar proteins. Among all proteins with evidence at transcript level, G protein coupled receptors and olfactory receptors, based on InterPro classification, were the largest families of proteins and exhibited more frequent variants. To identify missing proteins, the above analyses suggested including sequence variants in protein FASTA for database searching. Furthermore, evidence of unique peptides identified from MS experiments would be crucial for experimentally validating missing proteins. PMID- 26549056 TI - Echocardiographic Correlates of Abnormal Liver Tests in Patients with Exacerbation of Chronic Heart Failure. AB - BACKGROUND: Elevated total bilirubin (TB) and transaminases are frequently reported in patients with heart failure and are related to their worse prognosis. On the basis of hemodynamic data from previous studies, the investigators hypothesized that elevated bilirubin and transaminases are associated with different patterns of cardiac remodeling and dysfunction in patients with heart failure (i.e., elevated bilirubin with predominantly right-heart dysfunction and elevated transaminases with predominantly left-heart dysfunction). Therefore, the aim of this study was to evaluate prospectively echocardiographic correlates of elevated TB and transaminases on admission in patients with exacerbation of chronic heart failure. METHODS: The following echocardiographic parameters were prospectively analyzed in 150 patients (mean age, 75 years; 59% men): right ventricular end-diastolic diameter, right atrial area, tricuspid regurgitation, right ventricular systolic pressure, tricuspid annular plane systolic excursion, tricuspid lateral annulus systolic velocity, estimated right atrial pressure, portal vein pulsatility index (PVPI), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction, and cardiac index. RESULTS: Elevated TB was found in 61 patients (41%) and elevated transaminases in 46 patients (31%). In univariate logistic regression analysis, right ventricular end diastolic diameter, right atrial area, tricuspid regurgitation, estimated right atrial pressure, tricuspid annular plane systolic excursion, tricuspid lateral annulus systolic velocity, PVPI, left ventricular ejection fraction, and cardiac index were significant predictors of elevated TB (P < .05 for all). LVEDD indexed to body surface area, right ventricular end-diastolic diameter, and systolic blood pressure on admission were significant predictors of elevated transaminases (P < .05 for all). In a multivariate regression model, only PVPI remained a significant predictor of elevated TB and LVEDD indexed to body surface area of elevated transaminases. Sensitivity, specificity, and positive and negative predictive values of PVPI > 0.5 in the prediction of elevated TB were 81%, 87%, 82%, and 87%, respectively. CONCLUSION: Several echocardiographic indices of right-heart dysfunction and low cardiac index are related to elevated TB, with an increased PVPI having the best predictive value. A weak statistically significant association was found between elevated transaminase levels and left ventricular end-diastolic diameter indexed to body surface area. PMID- 26549057 TI - Audit of demand for after-hours CT scanning services in RANZCR-accredited training departments. AB - INTRODUCTION: The aims of this study were to measure: (i) the growth in after hours emergency department--referred CT (ED-CT) performed in accredited training departments between 2011 and 2013; (ii) the growth in ED CT relative to growth in ED presentations at the same hospitals; and (iii) trainee workload resulting from after-hours ED CT. METHODS: Ethics approval was obtained for all participating sites. Accredited training facilities in Australia and New Zealand with three or more trainees and serving one or more EDs were invited to participate (N = 32). Four nights were surveyed between August and December 2013. For data collection, the number of ED patients having one or more CT scans; ED CT scan total images; non-contrast head CTs; and ED patients (total and categories 1 and 2) attending the ED in the preceding 24 h and first half of calendar year were collected for 2013 and corresponding days in 2012 and 2011. Trainee staffing levels were measured. RESULTS: Eleven of 32 sites provided data for all four nights and 14 of 32 for one or more nights. A 15.7% increase in number of ED CTs between 1700 and 2200 h and 16.8% increase between 2201 and 0730 h occurred in the 2 years between 2011 and 2013 compared with a 6.9% increase in overall ED and 26% increase in categories 1 and 2 presentations over the same period. The number of CT images, however, increased 23%. CONCLUSION: Growth in demand by EDs for after-hours CT services has implications for service provision and trainee workloads in Royal Australian and New Zealand College of Radiologists-accredited training departments. PMID- 26549058 TI - Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter alpha-synuclein conformation and aggregation kinetics. AB - The interaction between nanoparticles (NPs) and the small intrinsically disordered protein alpha-synuclein (alphaSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that alphaSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the alphaSN secondary structure. In contrast, the weak interactions of alphaSN with HSA NPs allowed alphaSN to remain unfolded. These different levels of interactions had different effects on alphaSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of alphaSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing alphaSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety. PMID- 26549059 TI - From Editor's desk. PMID- 26549060 TI - Expression of apoptosis regulating proteins p53 and bcl-2 in psoriasis. AB - BACKGROUND: Dysfunctional apoptosis has an important role in the development of several skin diseases. Psoriatic keratinocytes possess an enhanced ability to resist apoptosis, which might be one of the key pathogenetic mechanisms in psoriasis. P53 and bcl-2 are two proteins which control apoptosis. Several studies have evaluated the expression of these two proteins in the psoriatic skin, but the results are controversial. METHODS: Fifty-eight cases of psoriatic skin biopsies were studied, and the grade of p53 and bcl-2 immunostaining was correlated with the histopathological indices of severity. RESULTS: Bcl-2 expression in the epidermis strongly correlated with the expression in the basal cells and lymphocytes (P--0.001 and 0.035). There was no correlation with epidermal hyperplasia or with p53 expression in the three compartments. Bcl-2 expression in the basal layer correlated with the p53 expression in the epidermis (P--0.027), basal layer (P--0.015) and the lymphocytes (P--0.034). There was a strong correlation among the p53 expression in all the compartments. There was also a weak correlation of the p53 expression in the epidermis with the epidermal hyperplasia (P--0.042). CONCLUSIONS: Bcl-2 does not appear to play an important role in the apoptotic process in psoriasis. In contrast, it is likely that p53 has a far more important role to play. Mutation analysis of the p53 protein is necessary to evaluate if the protein has mutated or if it is of the wild type. PMID- 26549061 TI - The differentiation of amebic colitis from inflammatory bowel disease on endoscopic mucosal biopsies. AB - BACKGROUND: Intestinal amebiasis is one of the important differential diagnoses of Inflammatory Bowel Disorders in areas where it is highly prevalent. AIM: Studies comparing the clinical, endoscopic and histological features of these disorders have never been done, so we undertook this study. MATERIALS AND METHODS: A retrospective study comparing mucosal biopsies of 14 consecutive cases of intestinal amebiasis with 14 cases of Ulcerative colitis and 12 cases of Crohn's disease. A total of 65 biopsies from patients with amebiasis, 56 biopsies from patients with Crohn's disease and 65 biopsies of patients with Ulcerative colitis were reviewed. RESULTS AND CONCLUSIONS: Discrete small ulcers less than 2 cm in diameter in the cecum or rectosigmoid, with intervening normal mucosa, were the most common finding on endoscopy in patients with amebiasis. On histology, necrotic material admixed with mucin, proteinaceous exudate and blood clot lining ulcers, significant surface epithelial changes such as shortening and tufting adjacent to sites of ulceration, mild chronic inflammation extending into the deep mucosa and mild architectural alteration were features of amebiasis. Trophozoite forms of ameba were seen in the necrotic material lining sites of ulceration or lying separately, as well as over intact mucosa. Necrotic material lining ulcers was less common in IBD, but chronic inflammation, crypt abscess formation and architectural alteration were more severe. PMID- 26549062 TI - 1p/14q co-deletion: A determinant of recurrence in histologically benign meningiomas. AB - BACKGROUND: Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors. MATERIALS AND METHODS: We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR), p53, and MIB-1. RESULTS: 18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III) with their parent tumors (14 grade I, 2 grade II and 2 grade III) were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI), PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence. CONCLUSION: Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I) meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion. PMID- 26549063 TI - Histopathological yield in different types of bronchoscopic biopsies in proven cases of pulmonary tuberculosis. AB - BACKGROUND: Diagnosis of pulmonary tuberculosis (TB) is difficult and often requires a lung biopsy. The goal of this retrospective study was to determine the histopathological parameters useful for diagnosis of pulmonary TB in different types of bronchoscopic biopsies (transbronchial lung biopsy [TBLB], transbronchial needle aspiration [TBNA], and bronchial biopsy [BB]). MATERIALS AND METHODS: The records of patients diagnosed to have pulmonary TB, over a period of 1-year were evaluated. Patients with positive acid-fast bacilli (AFB) culture and with three bronchoscopic biopsies including TBLB, TBNA, and BB were included in the study. Selected (14) histological parameters were evaluated retrospectively in a total of 27 biopsies from 9 patients with TB after hematoxylin-eosin and Ziehl-Neelsen staining. RESULTS: Diagnostic yield in TBLBs and TBNA was similar for granulomas detection (66.6% each). Granulomas in TBNA were larger, caseating and confluent as compared to small interstitial granulomas seen in TBLB. AFB was demonstrated in only one patient in TBNA. Lymphocytic cell cuffing was seen around most TBLB granulomas. One patient also showed microfilaria in blood vessel in TBLB. BBs in all patients showed the presence of goblet cell metaplasia and increased peribronchial plasma cell infiltrate with or without eosinophils may be indicative of chronic injury. The yield of granulomas was low in BBs seen in only 2 patients (22.2%). CONCLUSION: Diagnostic yield of TBNA and TBLB for granulomas was similar; however, caseation was seen more frequently in TBNA than on TBLB. Of other histological parameters, bronchial metaplastic changes and peribronchial plasma cells infiltrate were constant findings in all tubercular biopsies indicative of chronic injury. PMID- 26549064 TI - Fluorescent microscopy and Ziehl-Neelsen staining of bronchoalveolar lavage, bronchial washings, bronchoscopic brushing and post bronchoscopic sputum along with cytological examination in cases of suspected tuberculosis. AB - OBJECTIVES: Ever since the discovery of Mycobacterium tuberculosis in 1882, many diagnostic methods have been developed. However "The gold standard" for the diagnosis of tuberculosis (TB) is still the demonstration of acid fast Bacilli (AFB) by microscopic examination of smear or bacteriological confirmation by culture method. MATERIALS AND METHODS: In suspected 75 patients with active pulmonary TB, the materials obtained bronchoscopically, were bronchoalveolar lavage (BAL), bronchial brushings, bronchial washings and post bronchoscopic sputum. Four smears were made from each of the specimen. Fluorescent Staining, Ziehl-Neelsen (ZN), Pap and May Grunwald-Giemsa (MGG) stains were carried out for cytological examination. RESULTS: Fluorescent stain yielded maximum AFB positivity in all the methods, that is 36 (48%) in post fibre-optic bronchoscopy (FOB) sputum and 19 (25.33%) by fluorescence microscopy in both bronchial brushings and bronchial washings. Maximum yield of AFB with ZN staining 12 (16%) was equal to the post FOB sputum and bronchial brushings samples. It was followed by 6 cases (8%) in BAL and 4 (5.3%) in bronchial washings. The cytological examination was suggestive of TB in only 8 (10.66%) cases in bronchial washings and 6 (8%) cases in post FOB collection. It was equal in BAL and Bronchial brushings each that is 5 (6.67%). CONCLUSION: Bronchoscopy is a useful diagnostic tool and fluorescent microscopy is more sensitive than ZN and cytology. On X-ray examination, other diseases like malignancy or fungus can also mimick TB. So apart from ZN staining or fluorescence microscopy, Pap and MGG stain will be worthwhile to identify other microorganisms. PMID- 26549065 TI - Cytologic diagnosis of gastric submucosal lesions by endoscopic ultrasound-guided fine-needle aspiration: A single center experience in Saudi Arabia. AB - BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) sampling has become standard practice for the diagnosis of submucosal gastrointestinal (GI) lesions. The aim of this study was to determine the utility of EUS-guided FNA cytology in the diagnosis of deeply seated gastric mass lesions. MATERIALS AND METHODS: Thirteen patients with deeply seated gastric mass lesions were diagnosed by EUS-FNA. Adequate cytology material was present in all cases. Cell blocks were available in 10 cases. Surgical resections were performed in 8 cases. Immunohistochemical (IHC) studies were done on cell blocks in 9 cases and on 6 resected specimens. Seven cases has proved to be GI stromal tumors (GIST), in four of them, cell blocks were available, and resection for GIST was performed in 5 cases. IHC stains that were performed in cytology, as well as resection specimens, revealed similar results in each patient. CONCLUSION: EUS FNA cytology, when combined with a histologic assessment of cell blocks provides accurate and efficient tissue diagnosis of a wide variety of deeply seated gastric mass lesions. PMID- 26549066 TI - Evaluation of immunohistochemical subtypes in diffuse large B-cell lymphoma and its impact on survival. AB - BACKGROUND AND AIM: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in Indian population. The disease could be divided into the prognostically important subtypes, germinal center B-cell (GCB)-like and activated B-cell-like, using gene expression profiling (GEP). The molecular subtype as defined by GEP could also be predicted by using immunohistochemistry (IHC) based algorithms using three biomarkers CD10, BCL-6, and multiple myeloma oncogene-1 (MUM1). It has been confirmed that patients belonging to the GCB subtype have a better outcome and survival than those belonging to the second subtype. The present study was conducted to study the prevalence of these two subgroups and their correlation with survival of the patients. MATERIALS AND METHODS: A total of 83 patients of DLBCL were included in the study. Hematoxylin- and eosin-stained sections were prepared from the paraffin-embedded tissue blocks. The staining for all the three antibodies was considered positive when more than 30% cells were stained with the respective antibody. RESULTS: The results showed that 44 patients (53%) had GCB immunophenotype and 39 patients (47%) had non-GCB phenotype. However, no statistically significant difference in overall and disease-free survival was noted between the subgroups. CONCLUSION: This study demonstrated that frequency of GCB subtype of DLBCL is significantly higher than the non-GCB subtype, and the non-GCB immunophenotype has better relapse-free survival 78% (standard error = 0.10) at the end of 3 years, while GCB has 56% (standard error = 0.23). Further studies should be performed with larger number of patients to show difference in clinical outcome between GCB and non-GCB subgroups. PMID- 26549067 TI - Volume, conductivity, and scatter parameters as diagnostic aid to bacterial sepsis: A tertiary care experience. AB - INTRODUCTION AND MATERIALS AND METHODS: Early diagnosis of sepsis is extremely important to reduce high mortality and morbidity. In this study, clinical usefulness of the volume, conductivity and scatter parameters (mean channels of cell volume, conductivity, and light scatter) in neutrophils was analyzed for predicting acute bacterial infection, which are obtained by the Coulter LH 750 Hematology Analyzer (Beckman Coulter, Fullerton, CA, USA) during automated differential counts. RESULTS: Peripheral blood samples from 162 patients with positive blood cultures for bacteria and 40 healthy controls were studied. We observed a significant increase in the mean channel of neutrophil volume (MNV) from septic patients compared with control subjects (156 +/- 13.5 vs. 143 +/- 4.8; P < 001). DISCUSSION AND CONCLUSION: An elevation of the MNV was associated with a higher white blood cell count and percentage of neutrophils and was present even in patients who did not have leukocytosis or neutrophilia. With a cut-off of 149 for the MNV, a specificity of 91.4% and sensitivity of 88.7% were achieved. As a quantitative, objective, and more sensitive parameter, we propose that the MNV has a potential to be an additional indicator for acute bacterial infection. PMID- 26549068 TI - Association of virulence genes with mecA gene in Staphylococcus aureus isolates from Tertiary Hospitals in Nigeria. AB - INTRODUCTION: Staphylococcus aureus is the etiological agent for a wide range of human infections, and its pathogenicity largely depends on various virulence factors associated with adherence, evasion of the immune system and damage of the host. This study determined the prevalence of methicillin-resistant S. aureus (MRSA) and some selected virulence genes in clinical isolates of S. aureus from South-Western Nigeria. MATERIALS AND METHODS: The antibiotic susceptibility of 156 S. aureus isolates to various antibiotics was determined. Moreover, polymerase chain reaction detection of the mecA gene was performed including SCCmec typing, and the isolates were screened for selected genes (alpha hemolysin [hla], intracellular adhesion A [icaA], Panton-Valentine leukocidin [PVL], fibronectin binding protein A [fnbA], bone sialoprotein binding protein [bbp], exfoliative toxin A [eta], exfoliative toxin B [etb], and collagen binding adhesion [cna]) associated with virulence. RESULTS: The prevalence of mecA gene was 42.3% (66 out of 156 S. aureus), and SCCmec typing showed that 24 (36.4%) carried the SCCmec II element, 4 (6.1%) with type III, 10 (15.2%) with SCCmec IV, and 28 (42.4%) harbored type V. The proportion of S. aureus with the following genes was ascertained: Hla (55.1%), icaA (42.3%), PVL (34.6%), fnbA (8.3%), bbp (4.5%), and eta (3.8%). All the isolates were etb and cna negative. The prevalence of the PVL gene in methicillin susceptible Staphylococcus aureus (MSSA) was 53.3% compared with 9.1% of MRSA. An association between virulence genes (eta and icaA) and mecA positive S. aureus; and significant difference in the distribution of virulence genes in in-patients and out-patients were found. The MRSA strains in South-Western Nigeria were dominated by SCCmec II and SCCmec V. CONCLUSION: The study concluded that there is a high prevalence of MRSA in Nigeria with association of eta and icaA genes with mecA gene in S. aureus isolates. PMID- 26549069 TI - Study of clinical spectrum and risk factors of neonatal candidemia. AB - CONTEXT: Candida colonization in neonates results in significant morbidity and mortality. The prevalence and clinical significance of neonatal candidemia are poorly understood. AIMS: This study aimed to study clinical spectrum and risk factors of neonatal candidemia. SETTINGS AND METHODS: 108 cases of septicemia were studied. Blood samples were collected into Glucose broth and Bile broth, which are inoculated on Blood agar and MacConkey's agar and incubated at 37 degrees C for 7 days. Candida species were isolated were confirmed by standard techniques. STATISTICAL ANALYSIS USED: The data was collected and analyzed using by using SPSS IBM Company, Chicago, Version 16.0. RESULTS: 62 newborn patients who had a positive Candida blood culture. 47 (79.03%) were low birth weight and 37 (59.67%) were male. 19 (30.65%) were died. Candida species was a contributory factor to mortality in 14 (73.68%) patients. Among Candida isolates, Candida albicans was the commonest (65%) followed by Candida parapsilosis (15%) and Candida glabrata (10%). The risk factors like intrapartum use of antibiotics, vaginal delivery, low birth weight are identified in culture positive neonates. CONCLUSIONS: Candida species are assuming an increasing role in nosocomial infections in neonates and is associated with an increased risk of mortality. PMID- 26549070 TI - Comparison of biofilm formation in clinical isolates of Candida species in a tertiary care center, North India. AB - BACKGROUND AND OBJECTIVES: Biofilms are colonies of microbial cells encased in a self-produced organic polymeric matrix. The biofilm production is more important for nonalbicans Candida (NAC); as C. albicans possess many other mechanisms to establish infections. Correct identification of Candida species has gained importance due to persistent rise in infections caused by NAC. We sought to isolate, identify Candida species in clinical isolates and study biofilm formation. MATERIALS AND METHODS: Modified microtiter plate method was performed to study biofilm formation by isolates in Sabouraud's dextrose broth. It was then quantitatively assessed using a spectrophotometer. Biofilm formation was graded as negative, +1, +2, +3 and + 4 on the basis of percentage absorbance. RESULTS: Biofilm formation was observed in 16 of 40 (40.0%) isolates of C. albicans as compared to 39 of 78 (50.0%) of isolates of NAC. Strong (+4) biofilm production was seen in maximum biofilm producers in C. tropicalis (12 of 27) followed by C. albicans (8 of 16). Total biofilm producers were significantly more among high vaginal swab isolates 63.2% (12 of 19) and urine isolates 59.2% (29 of 49), when compared to blood isolates 34.2% (13 of 38) as well as other isolates 27.5% (11 of 40). INTERPRETATION AND CONCLUSIONS: NAC species are qualitatively and quantitatively superior biofilm producers than C. albicans. Biofilm production is the most important virulence factor of NAC species and compared to other lesions, it is more significantly associated with luminal infections. PMID- 26549071 TI - Immunofluorescence profile of discoid lupus erythematosus. AB - The direct immunofluorescence (DIF) of skin in conjunction with histopathology gives the best diagnostic yield. It is invaluable in confirming the diagnosis of small vessel vasculitides and bullous lesions of the skin and can be used as an additional tool to pinpoint the diagnosis of systemic and localized autoimmune diseases involving the skin. This study was undertaken to analyze the strength of DIF vis-a -vis histopathology in the diagnosis of discoid lupus erythematosus (DLE) and at the same time to elaborate the specific immunofluorescence findings in the lesions of DLE. The clinical profile and cutaneous lesions of 75 patients with DLE are described. DIF was positive in 68% and histopathology in 60% of cases. The most common immunoreactant was IgG at the dermoepidermal junction, followed by IgM and IgA. A conclusive diagnosis of DLE could be achieved satisfactorily in 64 cases (85%) by a combination of the two techniques. PMID- 26549072 TI - Extensive intestinal metaplasia of renal pelvis: Report of a case and literature review. AB - Transformation of the urothelium to the intestinal type of epithelium is rare in the pelvis with very few cases reported in the literature. The present study reports extensive intestinal metaplasia of the pelvi-calyceal system without residual urothelium in a 35-years-old woman with a 2 years history of renal calculi. Right - sided Nephrectomy was undertaken. Immunohistochemistry of the metaplastic epithelium revealed positive expression of CK20, low Ki-67 index and negative expression of p53. In this patient long standing metaplastic changes did not progress to adenocarcinoma which indicates that extensive intestinal metaplasia is not always associated with malignancy. PMID- 26549073 TI - Functional parathyroid cystic adenoma: A rare cause of hypercalcemic crisis with primary hyperparathyroidism. AB - We discuss a case of primary hyperparathyroidism caused by a giant cystic parathyroid adenoma presenting with neck swelling and hypercalcemic crisis. Fine needle aspiration cytology of presumed thyroid swelling from one of the two sites aspirated yielded clear fluid but was not attributed to parathyroid pathology. Elevated serum calcium and intact parathormone (iPTH) levels suggested preoperative parathyroid pathology. Ultrasound neck and sestamibi scan for parathyroid localization were not conclusive. Due to resistant hypercalcemia, the patient underwent emergency bilateral neck exploration and excision of the identified left superior parathyroid cyst along with total thyroidectomy. Monitoring of intra-operative iPTH helped complete removal of hyperfunctioning parathyroid tissue. Histopathological examination confirmed the parathyroid cyst. Cystic parathyroid adenoma should be considered in the differential diagnosis of cystic neck lesions. PMID- 26549074 TI - Mismatch repair protein deficient endometrioid adenocarcinomas, metastasizing to adrenal gland and lymph nodes: Unusual cases with diagnostic implications. AB - Recently, certain endometrial carcinomas have been found to be associated with mismatch repair (MMR) protein defects/deficiency. A 39-year-old female presented with cough, decreased appetite and significant weight loss since 2 months. Earlier, she had undergone total abdominal hysterectomy with bilateral salpingo oophorectomy (TAH-BSO) for endometrioid adenocarcinoma. Imaging disclosed an 8 cm sized adrenal mass that was surgically excised. Histopathology of the adrenal tumor, endocervical tumor, and endometrial biopsy revealed Federation of Gynecology and Obstetrics (FIGO) Grade II to III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were positive for cytokeratin 7, epithelial membrane antigen, PAX8, MLH1 and PMS2 while negative for estrogen receptor (ER), progesterone receptor (PR), MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. A 34-year-old lady presented with vaginal bleeding since 9 months. She underwent TAH-BSO, reported as FIGO Grade III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were negative for ER, PR, MLH1, and PMS2 while positive for MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. However, she developed multiple nodal and pericardial metastases and succumbed to the disease within a year post-diagnosis. Certain high-grade endometrioid adenocarcinomas occurring in younger women are MMR protein deficient and display an aggressive clinical course. Adrenal metastasis in endometrial carcinomas is rare. PMID- 26549075 TI - Extracavitary primary effusion lymphoma: A case report from India. AB - We present a case of extracavitary primary effusion lymphoma presenting, as jejunal polyps in a 38-year-old man. This is the first report of this entity from India. Although rare in our country, the diagnosis should be suspected in cases of CD20 negative large cell lymphoma with plasmablastic or immunoblastic differentiation in seropositive patients. Immunostaining for latency-associated nuclear antigen-1 and in situ hybridization for Epstein-Barr virus-associated RNA will confirm the diagnosis. PMID- 26549076 TI - A 36-year-old man with vomiting, pain abdomen, significant weight loss, hyponatremia, and hypoglycemia. AB - Diagnosis of Strongyloides stercoralis hyperinfection can be a challenge. The key to a timely diagnosis is to have a high index of suspicion. We present a rare case of a 36-year-old human immunodeficiency virus negative male patient, who was on multidrug therapy for lepromatous leprosy and was treated for type 2 lepra reactions with steroids in the past. The patient presented with vomiting and pain abdomen, persistent hyponatremia, and terminal hypoglycemia. He had features of malnutrition and had a rapid downhill course following admission. A diagnosis of S. stercoralis hyperinfection with sepsis and multiorgan failure, adrenal hemorrhage, and syndrome of inappropriate antidiuretic hormone secretion was established on a postmortem examination. PMID- 26549077 TI - Epithelial inclusion cyst of the cecum: A rare entity. AB - Epithelial inclusion cyst of the cecum (EICC) or epidermoid cyst of the cecum is extremely rare. Only seven cases of EICC have been reported in the English literature until now. A case of EICC is being reported in a 25-year-old female who presented with a pelvic mass associated with lower abdominal pain radiating to back. Abdominal contrast-enhanced computed tomography scan showed a well defined mass juxtaposed to cecum. During operation, a subserosal cystic mass was found adherent to the anterior wall of the cecum and confirmed to be an epithelial inclusion cyst histopathologically. It is being reported due to its extreme rarity. PMID- 26549078 TI - Anaplastic lymphoma kinase-positive pulmonary inflammatory myofibroblastic tumor with sarcomatous morphology and distant metastases: An unusual histomorphology and behavior. AB - Inflammatory myofibroblastic tumor (IMT), an intermediate-grade neoplasm of myofibroblastic/fibroblastic differentiation, occurs commonly in children and young adults. It is characterized by anaplastic lymphoma kinase (ALK) gene rearrangement and overexpression of ALK-protein. However, aggressive behavior is more commonly associated with ALK-negativity rather than ALK-positivity. Pulmonary involvement is most common visceral location and carries minimal potential for distant metastasis. We present a case of 49-year-old female with pulmonary IMT of spindle cell sarcomatous histomorphology. Frequent mitoses and necrosis with characteristic cytoplasmic immunoreactivity for ALK-1 protein and ALK-gene rearrangement on fluorescence in-situ hybridization were noted. This case is unusual for occurrence in higher age-group of fifth decade, sarcomatous histomorphology at presentation (rather than transformation) and metastases to distant sites despite ALK-protein overexpression and gene rearrangement. PMID- 26549079 TI - Spindle-cell ameloblastic carcinoma of the maxilla with adenoid cystic carcinoma like areas: A new variant? AB - Ameloblastic carcinoma is a rare aggressive malignancy of odontogenic epithelial origin. The disease has been reported to afflict people over a wide range of age group without any sex predilection. It is characterized by rapid growth and destruction of overlying bones along with involvement of adjacent soft tissues. The overall prognosis of this cancer is poor despite radical surgery and radiotherapy. Owing to the rarity of this lesion, complete data on the biological behavior and response to different treatment modalities are still lacking. The authors hereby report a case of this uncommon tumor arising from left maxilla in a 60-year-old Indian male. Histopathological examination of the tumor showed foci of spindling intermixed with large areas of tumor cells arranged in cribriform pattern and having luminal eosinophilic material which was reminiscent of adenoid cystic carcinoma. A final diagnosis was achieved after immunohistochemical study. These unusual findings prompted this case report. PMID- 26549080 TI - Adenoid cystic carcinoma of the trachea. AB - Primary salivary gland-type tumors of the lung and airways being unusual, they pose a diagnostic challenge on small biopsies and are usually consigned as non small cell lung carcinomas. Since the clinical behavior of these tumors is different from the conventional lung tumors, it is important to accurately diagnose them. Among this category of tumors, adenoid cystic carcinoma (ACC) of the lungs and airways is exceedingly rare. Few large studies and maximum case reports have been reported in literature on ACC of the lungs and trachea so far. We herein report a rare case of primary ACC of the trachea diagnosed on bronchoscopic biopsy. PMID- 26549081 TI - Malignancy of fallopian tube. PMID- 26549082 TI - Primary alveolar rhabdomyosarcoma of fallopian tube masquerading as a unilateral adnexal mass: A case report and literature review. AB - Rhabdomyosarcoma (RMS) is a high-grade sarcoma that predominantly affects children, and rarely, the adult population. RMS demonstrates three major histologic variants: Embryonal, alveolar, and pleomorphic. A limited number of documented pure RMS cases of the gynecologic organs in adult women are found in the literature. Of these reports, the fallopian tube (FT) is reported as the primary site in only three cases, those included one of embryonal and two of the pleomorphic histologic variants. Herein, we report the first case of alveolar RMS arising in the FT of an adult woman and presenting as a unilateral adnexal mass. PMID- 26549083 TI - Serous papillary cystadenofibroma of the fallopian tube: A case report and short review of literature. AB - Serous papillary cystadenofibromas (SPCAFs) of the fallopian tube are very rare benign tumors of the female genital tract. They are usually asymptomatic and are found incidentally. Until now, only 18 cases of this tumor have been reported in the world literature. We report a case of SPCAF of the left fallopian tube in a 30-year-old female who presented with a large abdominal mass and pain. On computed tomography, a diagnosis of ovarian neoplasm was given. However, during surgery the tumor was found to arise from the fallopian tube and was treated with tubal cystectomy with sparing of the ovary. We present this unique case on account of its rarity, unusual presentation, and huge size along with a short review of literature. PMID- 26549084 TI - Significance of fibrotic bands in utero--Amniotic band sequence with limb body wall complex: A rare case of fetal autopsy. AB - Amniotic band sequence (ABS) includes a wide spectrum of abnormalities resulting from entrapment of various fetal parts from a disrupted amnion, ranging from a mere constriction ring affecting a finger to a fatal form called limb body wall complex (LBWC). Reported cases of ABS with LBWC are very few. The spectrum of anomalies depends on which part gets entrapped and at what point of gestation. Hence, the clinical presentation can be extremely variable. Early detection of such cases using sonology is really challenging due to the small size of the fibrotic bands. Here, we present a case of amniotic band syndrome with LBWC in a fetus at 24 weeks of gestation, which was referred for an autopsy. The fetus also showed scoliosis, gastroschisis, lumbosacral meningocele, congenital talipes equinovarus, and cleft palate, thus having features of placenta cranial and placenta abdominal phenotype which is very rare. PMID- 26549085 TI - Primary intracardiac malignant peripheral nerve sheath tumor: A rare case report. AB - Myxomas are the most common benign cardiac tumors constituting approximately 75% of all the cardiac tumors. Rest 25% are malignant and sarcomas being the commonest. Among the sarcomas primary cardiac malignant peripheral nerve sheath tumors are extremely rare. They usually arise in relation to the branches of vagus or phrenic nerves, 5-42% being associated with neurofibromatosis type 1. Clinical signs and symptoms depend on the location and extent of involvement. Complete resection is the treatment of choice but local recurrence is common. PMID- 26549086 TI - Nevus sebaceus with basal cell carcinoma, poroma, and verruca vulgaris. AB - Nevus sebaceus (NS) is a congenital, benign, hamartomatous lesion and it is possible to see several benign or malignant tumors accompanying it. One of these is the poroma, which is very rare, and has only been reported twice before, in the English literature. In this paper, we presented two new cases of NS. One of them was a 40-year-old male who presented with a congenital skin lesion on his temporoparietal region. This lesion was composed of four different lesions, including NS, poroma, basal cell carcinoma (BCC), and verruca vulgaris. The second patient was a 41-year-old male presenting with a yellow-brown patch on the scalp. This lesion was comprised of NS and BCC. In addition to these presentations, we discussed the differential diagnosis between BCC and trichoblastoma, both of which are likely to be seen with NS. For this purpose, we recommended an immunohistological panel, which may be useful for differentiating these two morphologically similar lesions. PMID- 26549087 TI - Concomitant follicular lymphoma and histiocytic sarcoma: A rare progression, trans-differentiation or co-occurrence? AB - Trans-differentiation of follicular lymphoma (FL) into a histiocytic sarcoma (HS) is a rare event and usually occurs as a sequential event. We report a case where in the same node with two distinct areas one of low-grade FL and another with HS was observed. This patient was a 58 years old with generalized lymphadenopathy and Ann Arbor Stage III disease. The cervical node biopsy on histological examination revealed two distinct areas, firstly a FL with nodular architecture and the other a smaller focus of sheets of pleomorphic histiocytic cells diffusely arranged at the edge of the section contiguous with FL with few cells in transiting phase. On immunohistochemistry the FL was positive for CD20, CD10, PU.1, PAX5 and Bcl2, while the large histiocytic cells were positive for CD163, CD68, LCA, and PU.1, weakly for PAX5 and negative for CD20, CD10, CD30, CD3, CD1a, Bcl2, S100, and Alk-1. The therapeutic implications of this diagnosis and postulated theories on trans-differentiation are discussed. PMID- 26549088 TI - Pineal parenchymal tumor of intermediate differentiation. AB - The 2007 World Health Organization classification of tumors of the central nervous system identified "pineal parenchymal tumor of intermediate differentiation" (PPTID) as a new pineal parenchymal neoplasm, located between pineocytoma and pineoblastoma as grade II or III. Because of the small number of reported cases, the classification of PPT is still a matter of controversy. We report a case of PPTID. A 25-year-old female patient was admitted to hospital with complaints of a headache, nausea, vomiting since 1-year. Computed tomography/magnetic resonance imaging of the brain showed well-defined, mildly enhancing lesion in the region of the pineal gland with areas of calcification. The tumor was excised. After 3 years, she presented with metastasis in thoracic and lumbosacral spinal region. This is a rare event. PMID- 26549089 TI - Mixed adenoneuroendocrine carcinoma of the gallbladder, histopathological features. AB - An unusual case of mixed adenoneuroendocrine carcinoma is described which posed a diagnostic challenge in view of neuroendocrine component mimicking signet ring cells of adenocarcinoma. Diagnostic criteria for these mixed tumors, their histogenesis and treatment modalities are highlighted. PMID- 26549090 TI - Primary Burkitt's lymphoma of the breast without Epstein-Barr virus infection: A case report and literature review. AB - Burkitt lymphoma (BL) is a highly aggressive neoplasm, which arising from the germinal center or post germinal center B-cell. Primary breast lymphomas are extremely rare, and the most common histologic type is diffuse large B-cell lymphoma. Primary BL of the breast is much less common than the other types of lymphoma. Here, we report an extremely rare case of a 37-year-old Chinese female with localized bilateral breast, who was referred to our institution for bilateral breast swelling. The left breast tissue ultrasonography showed the short axis measuring 20.3 mm * 18.8 mm and the long axis measuring 22.1 mm * 20.8 mm soft tissue mass. The right breast tissue ultrasonography showed the short axis measuring 30.2 mm * 26.9 mm and the long axis measuring 33.5 mm * 2.18 mm. Coarse needle biopsy of breast masses demonstrated a non-Hodgkin's B-cell lymphoma. The patient underwent a bilateral mastectomy. Histological examination of the tumor showed a characteristic "starry sky" pattern, the medium-sized tumor cells were a monotonous pattern of growth, and there were many abnormal mitotic figures. The neoplastic cells strongly expressed CD20, CD79-MU, MUM-1, PAX-5, CD43 and Bcl-6, Ki-67 were nearly 100% positive, but negative for CD10, Bcl-2 and TdT. By fluorescence in situ hybridization an IGH-MYC gene fusion was detected in the tumor tissue which indicating the presence of a typical BL translocation t(8;14)(q24;q32). The final histopathological diagnosis was primary BL of the breast. PMID- 26549091 TI - Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature. AB - Lymphoepithelioma-like carcinoma (LELC) of the liver is uncommon, only 20 cases have been reported in the English-language literature so far, and the majority has been identified as cholangiocarcinomas, only four cases were hepatocellular LELC. Here we described a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC). A 42-year-old Chinese female who was incidentally found to have a liver-occupying lesion during a routine medical examination. Ultrasonography revealed a 47 mm * 33 mm * 36 mm hypoechoic mass in the left lobe. Computed tomography and magnetic resonance imaging displayed a nodular lesions in the left liver lobe. The patient underwent a left-side hepatectomy. Histopathological examination of the resected specimen revealed an undifferentiated carcinoma with a dense lymphocytic infiltrate, predominantly composed of CD3(+) T cells, morphologically similar to nasopharyngeal carcinoma. Immunohistochemically, the tumor cells were positive for CK, EMA, Glypican-3 and hepatocyte, but negative for alpha-fetoprotein, CK19, CK7 and CK20. Epstein-Barr virus (EBV) in situ hybridization was negative. The final histopathological diagnosis was lymphoepithelioma-like HCC without EBV infection. PMID- 26549092 TI - Glomangiopericytoma of nasal cavity. AB - Glomangiopericytoma/sinonasal type hemangiopericytoma is a rare sinonasal neoplasm arising from the pericytes surrounding capillaries and accounts for less than 0.5% of all sinonasal tumors. This tumor differs from conventional soft tissue hemangiopericytoma in location, biologic behaviour and histologic features. Glomangiopericytoma is a borderline low malignancy tumor with a good prognosis after complete surgical resection. We report a case of 60-year-old woman who presented with progressive nasal obstruction and frequent nasal bleeding and was diagnosed as glomangiopericytoma on histopathological and immunohistochemistry findings. Histological characteristics, differential diagnosis and prognosis of this tumor are discussed in this article. This case has been reported because of its rarity and an array of differential diagnosis. PMID- 26549093 TI - Endometrioid like yolk sac tumor of the testis with small teratomatous foci: A case report and review of the literature. AB - I have reported a case of endometrioid like yolk sac tumor of the testis in a 20 year-old boy. Endometrioid like yolk sac tumor is a rare tumor. A few cases have been reported in ovary. In case of male, a case of pure glandular endometrioid like yolk sac tumor is reported in a 43 years male in right undescended testis and another case of abdominal metastasis showing endometrioid pattern from mixed testicular germ cell tumor comprising of teratoma and embryonal carcinoma. My patient was a 20-year-old male presented with painless enlargement of right testis. Grossly the tumor was glistening creamish white with a multicystic appearance. Histopathological examination showed the tumor to be composed of glandular elements resembling early secretory endometrium, foci of keratinized thin squamous epithelium and a single focus of benign cartilage. The glandular elements show immunohistochemical positivity for AFP, cytokeratin 7 (CK7) and epithelial membrane antigen (EMA). PMID- 26549094 TI - An extraneural primary anaplastic ependymoma at the subcutaneous inguinal region: Report of a rare case. AB - Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm * 6.5 mm * 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region. PMID- 26549095 TI - Leishmaniasis in a patient with HIV co-infection: Diagnosis on fine needle aspiration cytology. AB - Leishmaniasis is a vector borne parasitic disease caused by obligate intracellular protozoa Leishmania and is transmitted by the bite of sand fly. The disease typically presents in visceral, cutaneous and mucocutaneous forms and is endemic in some states of India. Cases with atypical presentation are seen when patient has co- infection with HIV. We report a case of Leishmaniasis occurring in a HIV seropositive expectant mother diagnosed initially on fine needle aspiration cytology. The patient was resident of non endemic area and had presented with isolated cervical lymphadenopathy and fever without spleenomegaly. Characteristic morphological features of Leishmania seen in the fine needle aspiration smears from the neck nodes were identified and definitive diagnosis of Leishmaniasis could be given. Cytological features were not suggestive of any other disease. Timely diagnosis of the disease facilitated proper management in our patient. PMID- 26549096 TI - Cases of bowel schistosomiasis presenting as carcinoma colon. PMID- 26549097 TI - Quiz page. PMID- 26549098 TI - Discordant and metachronous Non-Hodgkin's lymphomas: Enteropathy-associated T cell lymphoma, Type II with aberrant expression of CD4 presenting several years after a mucosa-associated lymphoid tissue type B-cell lymphoma. PMID- 26549099 TI - High grade angiosarcoma of nasal cavity and paranasal sinuses: A rare case with immuno-histopathological study. PMID- 26549100 TI - Interference of hemoglobin D Punjab on measurements of glycated hemoglobin. PMID- 26549103 TI - Nanotribological and wetting performance of hierarchical patterns. AB - Surface modification is a promising method to solve the tribological problems in microsystems. To modify the surface, we fabricated hierarchical patterns with different pitches of nano-scale features and different surface chemistries. Micro and nano-patterns with similar geometrical configurations were also fabricated for comparison. The nano-tribological behavior of the patterns was investigated using an atomic force microscope at different relative humidity levels (5% to 80%) and applied normal loads (40 nN to 120 nN) under a constant sliding velocity. The results showed significant enhancement in the de-wetting and tribological performance of the hierarchical patterns compared with those of flat and micro- and nano-patterned surfaces. The PTFE-coated hierarchical patterns showed similar dynamic contact angles (advancing and receding) to those of the real lotus leaf. The influence of relative humidity on adhesion and friction behavior was found to be significant for all the tested surfaces. The tribological performance was improved as the pitch of the nano-scale geometry of the hierarchical pattern increased, even though the wetting property was not influenced significantly. A model was proposed based on the role of intermolecular force to explain the effect of the pitch of the hierarchical patterns on the adhesion and friction behavior. According to the model based on the molecular force, the contact between a ball and the patterned surface was a multi-asperity contact, contrary to the single-asperity contact predicted by the Johnson-Kendall-Roberts (JKR) and Maugis-Dugdale (MD) models. The strong intermolecular forces, which are activated in the confined spaces between the adjacent nano-pillars and the ball, contributed to the contact area and hence the adhesion and friction forces. PMID- 26549102 TI - X-ray structure and activities of an essential Mononegavirales L-protein domain. AB - The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-A X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2'O and N7 positions, and also displays nucleotide triphosphatase activity. PMID- 26549104 TI - Click Chemistry Applied to the Synthesis of Salmonella Typhimurium O-Antigen Glycoconjugate Vaccine on Solid Phase with Sugar Recycling. AB - A solid-phase conjugation method was developed and applied to the synthesis of an O-antigen based glycoconjugate vaccine against Salmonella Typhimurium, with CRM197 as the carrier protein. Copper-free click chemistry was used as the conjugation chemistry, after derivatizing the sugar and the protein components with alkyne and azido linkers, respectively. This chemistry has the advantage of not deactivating functional groups during the conjugation step, thereby allowing the recycling of unreacted components. The activated carrier protein was adsorbed to an anion exchange matrix and quantitatively conjugated to the O-antigen. The resulting conjugate was eluted from the resin free of unconjugated sugar which was previously removed by simple washing steps. Unreacted O-antigen was recycled by addition to a new batch of resin-CRM197 resulting in further quantitative protein conjugation. This process has advantages in relation to reduction of costs for production of conjugate vaccines, allowing unreacted sugar recovery and simplifying the purification of the glycoconjugate. PMID- 26549106 TI - Phosphorylation of eIF2alpha Is a Translational Control Mechanism Regulating Muscle Stem Cell Quiescence and Self-Renewal. AB - Regeneration of adult tissues depends on somatic stem cells that remain quiescent yet are primed to enter a differentiation program. The molecular pathways that prevent activation of these cells are not well understood. Using mouse skeletal muscle stem cells as a model, we show that a general repression of translation, mediated by the phosphorylation of translation initiation factor eIF2alpha at serine 51 (P-eIF2alpha), is required to maintain the quiescent state. Skeletal muscle stem cells unable to phosphorylate eIF2alpha exit quiescence, activate the myogenic program, and differentiate, but do not self-renew. P-eIF2alpha ensures in part the robust translational silencing of accumulating mRNAs that is needed to prevent the activation of muscle stem cells. Additionally, P-eIF2alpha dependent translation of mRNAs regulated by upstream open reading frames (uORFs) contributes to the molecular signature of stemness. Pharmacological inhibition of eIF2alpha dephosphorylation enhances skeletal muscle stem cell self-renewal and regenerative capacity. PMID- 26549105 TI - Tissue Strain Reorganizes Collagen With a Switchlike Response That Regulates Neuronal Extracellular Signal-Regulated Kinase Phosphorylation In Vitro: Implications for Ligamentous Injury and Mechanotransduction. AB - Excessive loading of ligaments can activate the neural afferents that innervate the collagenous tissue, leading to a host of pathologies including pain. An integrated experimental and modeling approach was used to define the responses of neurons and the surrounding collagen fibers to the ligamentous matrix loading and to begin to understand how macroscopic deformation is translated to neuronal loading and signaling. A neuron-collagen construct (NCC) developed to mimic innervation of collagenous tissue underwent tension to strains simulating nonpainful (8%) or painful ligament loading (16%). Both neuronal phosphorylation of extracellular signal-regulated kinase (ERK), which is related to neuroplasticity (R2 >= 0.041; p <= 0.0171) and neuronal aspect ratio (AR) (R2 >= 0.250; p < 0.0001), were significantly correlated with tissue-level strains. As NCC strains increased during a slowly applied loading (1%/s), a "switchlike" fiber realignment response was detected with collagen reorganization occurring only above a transition point of 11.3% strain. A finite-element based discrete fiber network (DFN) model predicted that at bulk strains above the transition point, heterogeneous fiber strains were both tensile and compressive and increased, with strains in some fibers along the loading direction exceeding the applied bulk strain. The transition point identified for changes in collagen fiber realignment was consistent with the measured strain threshold (11.7% with a 95% confidence interval of 10.2-13.4%) for elevating ERK phosphorylation after loading. As with collagen fiber realignment, the greatest degree of neuronal reorientation toward the loading direction was observed at the NCC distraction corresponding to painful loading. Because activation of neuronal ERK occurred only at strains that produced evident collagen fiber realignment, findings suggest that tissue strain-induced changes in the micromechanical environment, especially altered local collagen fiber kinematics, may be associated with mechanotransduction signaling in neurons. PMID- 26549107 TI - Functional Connectivity under Optogenetic Control Allows Modeling of Human Neuromuscular Disease. AB - Capturing the full potential of human pluripotent stem cell (PSC)-derived neurons in disease modeling and regenerative medicine requires analysis in complex functional systems. Here we establish optogenetic control in human PSC-derived spinal motorneurons and show that co-culture of these cells with human myoblast derived skeletal muscle builds a functional all-human neuromuscular junction that can be triggered to twitch upon light stimulation. To model neuromuscular disease we incubated these co-cultures with IgG from myasthenia gravis patients and active complement. Myasthenia gravis is an autoimmune disorder that selectively targets neuromuscular junctions. We saw a reversible reduction in the amplitude of muscle contractions, representing a surrogate marker for the characteristic loss of muscle strength seen in this disease. The ability to recapitulate key aspects of disease pathology and its symptomatic treatment suggests that this neuromuscular junction assay has significant potential for modeling of neuromuscular disease and regeneration. PMID- 26549108 TI - Fighting cancer together: Development and implementation of shared medical appointments to standardize and improve chemotherapy education. AB - OBJECTIVE: Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. METHODS: We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. RESULTS: From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. CONCLUSIONS: This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted. PMID- 26549109 TI - Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer. AB - OBJECTIVE: Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. METHODS: Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. RESULTS: Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). CONCLUSIONS: Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. PMID- 26549111 TI - Developing Students as Future Researchers Using QSEN Competencies as a Framework. AB - PURPOSE: This article discusses the development of students as future researchers within the context of carrying out an R-15-funded research project, and demonstrates the application of selected competencies from the Quality and Safety Education for Nursing project as a project framework. Operationally, the project had two parallel tracks; the first track was the research project itself, and the second track was the development of researchers through carrying out the research project. OBJECTIVES OF THE PROJECT: The objectives of the research project were to (a) translate project documents into Spanish, (b) test the acceptability of the intervention in a Hispanic population along the Unites States-Mexico border, and (c) assess the feasibility of conducting a trial of the intervention in the same population. METHOD: Development of future researchers was guided by selected pre-licensure Quality and Safety Education for Nursing competencies, which created a transparent link among research, education, and practice. CONCLUSION: This framework is extremely useful for educators and research mentors who have the opportunity to mentor and develop students as researchers. Monsivais Robinson. PMID- 26549110 TI - TIMP-1 mediates TGF-beta-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. AB - Transforming growth factor-beta (TGF-beta) signaling plays a key role in progression and metastasis of HCC. This study was undertaken to gain the proof of concept of a small-molecule inhibitor of TGF-beta type I receptor kinase, EW-7197 as a potent anti-cancer therapy for HCC. We identified tissue inhibitors of metalloproteinases-1 (TIMP-1) as one of the secreted proteins of hepatic stellate cells (HSCs) and a key mediator of TGF-beta-mediated crosstalk between HSCs and HCC cells. TGF-beta signaling led to increased expression of TIMP-1, which activates focal adhesion kinase (FAK) signaling via its interaction with CD63. Inhibition of TGF-beta signaling using EW-7197 significantly attenuated the progression and intrahepatic metastasis of HCC in an SK-HEP1-Luc orthotopic xenograft mouse model. In addition, EW-7197 inhibited TGF-beta-stimulated TIMP-1 secretion by HSCs as well as the TIMP-1-induced proliferation, motility, and survival of HCC cells. Further, EW-7197 interrupted TGF-beta-mediated epithelial to-mesenchymal transition and Akt signaling, leading to significant reductions in the motility and anchorage-independent growth of HCC cells. In conclusion, we found that TIMP-1 mediates TGF-beta-regulated crosstalk between HSCs and HCC cells via FAK signaling. In addition, EW-7197 demonstrates potent in vivo anti cancer therapeutic activity and may be a potential new anti-cancer drug of choice to treat patients with liver cancer. PMID- 26549112 TI - Erratum to: Mass spectrometric analysis of products of metabolic glycan engineering with azido-modification of sialic acids. PMID- 26549113 TI - Erratum to: Intact cell mass spectrometry as a rapid and specific tool for the differentiation of toxic effects in cell-based ecotoxicological test systems. PMID- 26549114 TI - Ethyl glucuronide concentrations in hair: a controlled alcohol-dosing study in healthy volunteers. AB - Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of >=7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the non-drinking group had median EtG concentrations of 0.5 pg/mg hair (interquartile range (IQR) 1.7 pg/mg; range < 0.21-4.5 pg/mg). Participants consuming 100 and 150 g alcohol per week showed median EtG concentrations of 5.6 pg/mg hair (IQR 4.7 pg/mg; range 2.0 9.8 pg/mg) and 11.3 pg/mg hair (IQR 5.0 pg/mg; range 7.7-38.9 pg/mg), respectively. Hair EtG concentrations between the three study groups differed significantly from one another (p < 0.001). Hair EtG concentrations can be used to differentiate between repeated (low-to-moderate) amounts of alcohol consumed over a long time period. For the assessment of repeated alcohol use, we propose that the current cut-off of 7 pg/mg could be re-evaluated. PMID- 26549115 TI - An in-depth evaluation of accuracy and precision in Hg isotopic analysis via pneumatic nebulization and cold vapor generation multi-collector ICP-mass spectrometry. AB - Mercury (Hg) isotopic analysis via multi-collector inductively coupled plasma (ICP)-mass spectrometry (MC-ICP-MS) can provide relevant biogeochemical information by revealing sources, pathways, and sinks of this highly toxic metal. In this work, the capabilities and limitations of two different sample introduction systems, based on pneumatic nebulization (PN) and cold vapor generation (CVG), respectively, were evaluated in the context of Hg isotopic analysis via MC-ICP-MS. The effect of (i) instrument settings and acquisition parameters, (ii) concentration of analyte element (Hg), and internal standard (Tl)-used for mass discrimination correction purposes-and (iii) different mass bias correction approaches on the accuracy and precision of Hg isotope ratio results was evaluated. The extent and stability of mass bias were assessed in a long-term study (18 months, n = 250), demonstrating a precision <=0.006% relative standard deviation (RSD). CVG-MC-ICP-MS showed an approximately 20-fold enhancement in Hg signal intensity compared with PN-MC-ICP-MS. For CVG-MC-ICP-MS, the mass bias induced by instrumental mass discrimination was accurately corrected for by using either external correction in a sample-standard bracketing approach (SSB) or double correction, consisting of the use of Tl as internal standard in a revised version of the Russell law (Baxter approach), followed by SSB. Concomitant matrix elements did not affect CVG-ICP-MS results. Neither with PN, nor with CVG, any evidence for mass-independent discrimination effects in the instrument was observed within the experimental precision obtained. CVG-MC-ICP-MS was finally used for Hg isotopic analysis of reference materials (RMs) of relevant environmental origin. The isotopic composition of Hg in RMs of marine biological origin testified of mass-independent fractionation that affected the odd-numbered Hg isotopes. While older RMs were used for validation purposes, novel Hg isotopic data are provided for the latest generations of some biological RMs. PMID- 26549116 TI - Affinity interactions of human immunoglobulin G with short peptides: role of ligand spacer on binding, kinetics, and mass transfer. AB - The interaction affinity between human IgG and a short peptide ligand (hexameric HWRGWV) was investigated by following the shifts in frequency and energy dissipation in a quartz crystal microbalance (QCM). HWRGWV was immobilized by means of poly(ethylene glycol) tethered on QCM sensors coated with silicon oxide, which enhanced the accessibility of the peptide to hIgG and also passivated the surface. Ellipsometry and ToF-SIMS were employed for surface characterization. The peptide ligand density was optimized to 0.88 chains nm(-2), which enabled the interaction of each hIgG molecule with at least one ligand. The maximum binding capacity was found to be 4.6 mg m(-2), corresponding to a monolayer of hIgG, similar to the values for chromatographic resins. Dissociation constants were lower than those obtained from resins, possibly due to overestimation of bound mass by QCM. Equilibrium thermodynamic and kinetic parameters were determined, shedding light on interfacial effects important for detection and bioseparation. Graphical Abstract The interaction affinity between human IgG and a short peptide ligand was investigated by using quartz crystal microgravimetry, ellipsometry and ToF-SIMS. Equilibrium thermodynamic and kinetics parameters were determined, shedding light on interfacial effects important for detection and bioseparation. PMID- 26549117 TI - Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector. AB - In this work, we utilize a short-wavelength, 532-nm picosecond pulsed laser coupled with a time-gated complementary metal-oxide semiconductor (CMOS) single photon avalanche diode (SPAD) detector to acquire Raman spectra of several drugs of interest. With this approach, we are able to reveal previously unseen Raman features and suppress the fluorescence background of these drugs. Compared to traditional Raman setups, the present time-resolved technique has two major improvements. First, it is possible to overcome the strong fluorescence background that usually interferes with the much weaker Raman spectra. Second, using the high photon energy excitation light source, we are able to generate a stronger Raman signal compared to traditional instruments. In addition, observations in the time domain can be performed, thus enabling new capabilities in the field of Raman and fluorescence spectroscopy. With this system, we demonstrate for the first time the possibility of recording fluorescence suppressed Raman spectra of solid, amorphous and crystalline, and non photoluminescent and photoluminescent drugs such as caffeine, ranitidine hydrochloride, and indomethacin (amorphous and crystalline forms). The raw data acquired by utilizing only the picosecond pulsed laser and a CMOS SPAD detector could be used for identifying the compounds directly without any data processing. Moreover, to validate the accuracy of this time-resolved technique, we present density functional theory (DFT) calculations for a widely used gastric acid inhibitor, ranitidine hydrochloride. The obtained time-resolved Raman peaks were identified based on the calculations and existing literature. Raman spectra using non-time-resolved setups with continuous-wave 785- and 532-nm excitation lasers were used as reference data. Overall, this demonstration of time-resolved Raman and fluorescence measurements with a CMOS SPAD detector shows promise in diverse areas, including fundamental chemical research, the pharmaceutical setting, process analytical technology (PAT), and the life sciences. PMID- 26549119 TI - A critical look at persistent problems in the diagnosis, staging and treatment of temporal bone carcinoma. AB - Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a distinctly poor prognosis in advanced cases. There is still much controversy surrounding the rational diagnostic/therapeutic approach to TBSCC. Diagnostic differences are due mainly to: the small number of cases reported (even in the largest available series); the inappropriate histological heterogeneity of several case series; the lack of an internationally-accepted staging system for TBSCC; the frequent absence of adequate radiological imaging to enable a malignancy's local, regional and distant extension to be studied in detail; and a non-standardized approach to final histological assessment of the surgical margins. As for the therapeutic approaches, several issues are still debated, including the choice between en bloc and piecemeal primary surgery for the tumor's removal, and the role of elective neck dissection. Although radiotherapy seems to be an effective adjuvant therapy in advanced cases, its role in low stage tumors or as a primary treatment has yet to be established. The value of chemotherapy is also still unclear. The treatment strategy for TBSCC is often based on the combined experience of a given surgeon and institution, bearing the results reportedly achieved by other oncology centers in mind. To date, the optimal management of TBSCC is still elusive. We aimed to critically review the ongoing crucial issues concerning the management of TBSCC, analyzing how it is diagnosed, staged and treated, the management of recurrences, rational follow-up schedules, and prognostic factors for this disease. PMID- 26549118 TI - Increased Delay Discounting on a Novel Real-Time Task among Girls, but not Boys, with ADHD. AB - The aim of this study was to examine delay discounting in girls and boys with ADHD-Combined type (ADHD-C) relative to typically developing (TD) children on two tasks that differ in the extent to which the rewards and delays were experienced by participants. Children ages 8-12 years with ADHD-C (n=65; 19 girls) and TD controls (n=55; 15 girls) completed two delay discounting tasks involving a series of choices between smaller, immediate and larger, delayed rewards. The classic delay discounting task involved choices about money at delays of 1-90 days and only some of the outcomes were actually experienced by the participants. The novel real-time discounting task involved choices about an immediately consumable reward (playing a preferred game) at delays of 25-100 s, all of which were actually experienced by participants. Participants also provided subjective ratings of how much they liked playing the game and waiting to play. Girls with ADHD-C displayed greater delay discounting compared to boys with ADHD-C and TD girls and boys on the real-time discounting task. Diagnostic group differences were not evident on the classic discounting task. In addition, children with ADHD C reported wanting to play the game more and liking waiting to play the game less than TD children. This novel demonstration of greater delay discounting among girls with ADHD-C on a discounting task in which the rewards are immediately consumable and the delays are experienced in real-time informs our understanding of sex differences and motivational processes in children with ADHD. (JINS, 2016, 22, 12-23). PMID- 26549120 TI - Potential of lactic acid bacteria at regulating Escherichia coli infection and inflammation of bovine endometrium. AB - About 40% of dairy cattle develop uterine disease during postpartum period, causing infertility. Some studies indicate that uterine infection, predominantly by Escherichia coli in the first week postpartum, is associated with metritis, an uterus inflammation in which the cow fails to completely clear bacterial contaminants. The aim of this study was to evaluate the potential of four lactic acid bacteria (LAB) (Lactobacillus rhamnosus, Pediococcus acidilactici, Lactobacillus reuteri, and Lactobacillus sakei) to modulate the E coli infection and inflammation in endometrial cells. Primary endometrial epithelial cells were isolated from fresh endometrium of a healthy cow and cultured in vitro to evaluate the effects of LAB at three different doses. Cell extracts were obtained to analyze the expression of proinflammatory cytokines and to quantify E coli infection on MacConkey agar plates. L sakei and L reuteri showed a positive effect preventing E coli infection (87% and 78%, respectively, P < 0.001); however, they were also associated to a dose-variable effect on tissular inflammation that could further exacerbate the proinflammatory status. Infection of E coli was clearly reduced (P < 0.001) up to an 83% with P acidilactici, whereas, the expression of proinflammatory cytokines IL-8 and IL-1beta dropped significantly (P < 0.001) up to 85.11 and 5.24 folds, respectively, in the presence of L rhamnosus. In conclusion, these results demonstrate a clear potential of some LAB in the modulation of endometrial infection and inflammation in cattle. PMID- 26549121 TI - Effect of freezing rate for cryopreservation of Persian sturgeon (Acipenser persicus) spermatozoa. AB - This study examined the effect of freezing rate (-10 degrees C, -15 degrees C, 20 degrees C, -30 degrees C, and -40 degrees C/min) on motility parameters, rates of fertilization and hatching, ATP content, and indices of oxidative stress including thiobarbituric acid reactive substances and carbonyl derivatives of proteins in Persian sturgeon (Acipenser persicus) sperm. After sampling, sperm was diluted in an extender composed of 23.4-mM sucrose, 0.25-mM KCl, and 30-mM Tris-HCl, pH 8.0, containing 10% methanol and subsequently frozen in a programmable freezer. For postthaw sperm that were frozen at a rate of -40 degrees C/min, sperm motile duration (134 +/- 27.01 seconds), sperm motile percent (60 +/- 4.1%), fertilizability (72 +/- 8.36% for fertilization rate and 65 +/- 7.58% for hatching rate), and ATP content (4.8 +/- 0.57 nmol/10(8) sperm) were significantly higher than for sperm frozen at any of the four slower rates (P < 0.05). Moreover, sperm cryopreserved using the fastest freezing rate had significantly lower levels of thiobarbituric acid reactive substances (0.5 +/- 0.05 nmol/10(8) sperm) and carbonyl derivatives of proteins (41.3 +/- 4.9 nmol/10(8) sperm) than sperm cryopreserved using all other freezing rates (P < 0.05). In addition, there is a significant difference (P < 0.05) between fresh sperm and the recovery of cryopreserved Persian sturgeon sperm using programmable freezing with -40 degrees C/min being the optimal freezing rate among those tested. PMID- 26549122 TI - Ultrasonographic examination reduces the percentage of unsuccessful inseminations in dairy cows. AB - The objective of this study was to investigate whether confirmation of suitability for service by traditional methods, observation and transrectal palpation, is improved in cattle by additional ultrasonographic examination of the uterus and ovaries. The data from 600 lactating cows from Southern Germany submitted for the first service and alternately assigned to manual (group M, n = 301) and manual and sonographic examination (group S, n = 299) were evaluated. Cows of group M with a large, soft follicle with an estimated diameter of 12.0 to 22.5 mm, without a palpable CL (>10 mm), and with a contractile uterus without palpable content were considered suitable for service and inseminated. Cows of group S with a soft follicle measuring 12.0 to 22.5 mm, without a CL (>10 mm), and with a contractile uterus and no echoic content were inseminated. Pregnancy was determined by ultrasonography at 28 to 35 days after the first service. In group S, 10.9% fewer cows (P = 0.003) were considered suitable for service than in group M. The main reason (29.6%) for exclusion from service in group S was the presence of a CL greater than 10 mm in addition to a preovulatory follicle (12.0 22.5 mm), which was diagnosed less frequently in group M (4.5%; P < 0.0001). The first-service conception rate tended to be higher in group S than in group M (62.7% vs. 54.9%; P = 0.10), and the percentage of open cows, based on all cows submitted for service, was higher in group M than in group S (35.2% vs. 25.1%; P = 0.007). We concluded that sonographic examination of cows submitted for service facilitates the exclusion from service of proestrous and diestrous cows and reduces the number of pointless services. PMID- 26549123 TI - Dietary n-3 PUFAs improve fresh and post-thaw semen quality in Holstein bulls via alteration of sperm fatty acid composition. AB - The goal of this study was to investigate the effect of fish oil-supplemented diet on fresh and post-thaw semen quality and sperm lipid composition in bulls. Bulls were randomly assigned to two groups (n = 6). Six bulls were used as the control group and six received the fish oil (1.2% dry matter of total diet) for 11 weeks. Semen was individually collected from each bull and frozen biweekly. Semen volume, sperm concentration, viability, progressive motility, and fatty acid profile of sperm were measured in 1st, 3rd, 5th, 7th, 9th, and 11th week of experiment. Viability, progressive motility, and fatty acid profile of post-thaw sperm were also measured in 3rd, 5th, 9th, and 11th week of experiment. Data were analyzed with using Proc GLM or MIXED (for repeated measurement data) in SAS program. The fish oil-supplemented diet increased the semen volume and sperm concentration. The fish oil-supplemented diet also altered the viability, progressive motility, and fatty acid profile of fresh and post-thaw sperm. In conclusion, feeding a fish oil-enriched diet via alteration of fatty acid profile of sperm lipid could improve in vitro quality of fresh and post-thaw sperm in Holstein bulls. PMID- 26549124 TI - Polo-like kinase 4 regulates spindle and actin assembly in meiosis and influence of early embryonic development in bovine oocytes. AB - PLK4, a polo-like kinase (PLK) family member that accumulates in the cytoplasm, has been identified as a crucial regulator of centriole formation. PLK4 also controls several essential cellular functions, including cytokinesis and gene expression. In this study, we investigated the expression and function of PLK4 during bovine oocyte meiotic maturation and subsequent embryo development. The PLK4 mRNA was detected in bovine oocytes at all developmental stages during meiotic maturation. Immunofluorescence staining showed that PLK4 protein exhibited a dynamic localization pattern in the oocyte cytoplasm during meiotic maturation, and fluorescence immunostaining markedly increased in metaphase II. When an interfering double-stranded RNA targeting PLK4 was injected into germinal vesicle-stage oocytes, PLK4 transcript levels decreased significantly in metaphase II oocytes (P < 0.05). The PLK4 knockdown caused spindle defects and chromosome misalignment and considerably reduced the amount of cortical and cytoplasmic actin. PLK4 was localized in the cytoplasm of early embryos, and PLK4 knockdown in germinal vesicle-stage oocytes led to failure in the early development of in vitro fertilized embryos (P < 0.05). Taken together, these results indicated that PLK4 plays crucial roles in bovine oocyte meiotic maturation and subsequent early embryo development. PMID- 26549125 TI - Factors affecting the size of ovulatory follicles and conception rate in high yielding dairy cows. AB - Two studies were designed to determine (1) the effects of Heatsynch and Ovsynch protocols versus spontaneous ovulation and (2) the effects of calving problems, clinical uterine infections, and clinical mastitis on the size of the ovulatory follicle, conception rate, and embryonic/fetal (E/F) death in high-yielding dairy cows. In study 1, cows without the history of calving problems, clinical uterine infections, and clinical mastitis were randomly allocated to either an Ovsynch (n = 45) or Heatsynch (n = 39) ovulation synchronization protocol or spontaneous ovulation (n = 43) groups. Blood samples were collected on the day of artificial insemination (AI) to measure progesterone (P4), estradiol-17beta, and insulin like growth factor 1 (IGF-1) and 7 days later to measure P4. Study 2 consisted of cows (n = 351) with or without the history of calving problems, clinical uterine infections, and clinical mastitis which were artificially inseminated after a 55 day voluntary waiting period. Transrectal ultrasonography was performed at the time of AI to measure the ovulatory follicle size and on Days 30 and 68 after AI to diagnose pregnancy in both studies. In study 1, the mean (+/-standard error of the mean) diameter of the ovulatory follicle was greater (P = 0.0005) and E/F mortality was lower (P = 0.007) for the spontaneous ovulation group compared with Ovsynch and Heatsynch groups. Serum concentration of P4 on Day 7 after AI was correlated with the size of the ovulatory follicle (P = 0.007). Conception rate at Days 30 and 68 was not significantly different between the three experimental groups in study 1. Cows with serum IGF-1 concentrations greater than 55 ng/mL at AI had significantly higher Day 68 conception rate (50% vs. 24%) and lower E/F death (16.6% vs. 40%) compared to cows with serum IGF-1 concentrations lower than 56 ng/mL at AI. The conception rate on Days 30 and 68 for follicles of 10 to 14 mm in diameter (34% and 21.8%) was significantly lower than follicles of 14.1 to 19 mm in diameter (60% and 50%), respectively (P < 0.05). In study 2, the ovulatory follicle in cows with clinical uterine infections was smaller than that in cows without clinical uterine infections (16.4 vs. 17.1 mm; P = 0.04). In conclusion, the size of the ovulatory follicle is affected by ovulation synchronizing protocols and postpartum clinical uterine infections. In addition, cows with higher serum IGF-1 concentrations on the day of AI had higher Day 68 conception rate and lower E/F death. PMID- 26549126 TI - Urocortin 1 expression and secretion by human umbilical vein endothelial cells: In vitro effects of interleukin 8, interferon gamma, lipopolysaccharide, endothelin 1, prostaglandin F-2alpha, estradiol, progesterone and dexamethasone. AB - Urocortin 1 (Ucn1) is a 40-amino-acid peptide that has vasodilatory activity and displays immunomodulatory and antioxidant properties. Maternal and cord plasma Ucn1 levels are increased in preeclampsia and preterm labor, but the mechanisms of such increase are poorly known. Thus, we investigated Ucn1 localization in human umbilical cord and assessed some potential stimuli to Ucn1 release by human umbilical vein endothelial cells (HUVEC). Human umbilical cords were obtained at uncomplicated term pregnancy (n=11). Ucn1 localization was assessed by immunohistochemistry and quantified. HUVEC were grown in vitro to confluence, then incubated with serial concentrations of interleukin (IL)-8, interferon (INF) gamma, lipopolysaccharide (LPS), endothelin (ET)-1, prostaglandin (PG)F-2alpha, estradiol, progesterone and dexamethasone and Ucn1 concentrations were measured in the supernatants. Ucn1 was immunolocalized with similar intensity in umbilical cord arteries, vein and Wharton's jelly. Ucn1 mRNA was detected in all HUVEC cultures and Ucn1 peptide was detectable in culture medium from untreated cells at different time points. Incubation with IFN-gamma increased Ucn1 secretion in a dose-dependent manner. Treatments with IL-8, LPS, ET-1 and dexamethasone were able to increase three to fourfold Ucn1 release from cultured endothelial cells. In conclusion, umbilical vessels express Ucn1 and may be a contributive source of Ucn1 release into fetal-placental circulation. IL-8, IFN-gamma, LPS, ET-1 and dexamethasone promote Ucn1 secretion from cultured HUVEC. PMID- 26549127 TI - Diet-delivered RNAi in Helicoverpa armigera--Progresses and challenges. AB - Helicoverpa armigera (the cotton bollworm) is a significant agricultural pest endemic to Afro-Eurasia and Oceania. Gene suppression via RNA interference (RNAi) presents a potential avenue for management of the pest, which is highly resistant to traditional insecticide sprays. This article reviews current understanding on the fate of ingested double-stranded RNA in H. armigera. Existing in vivo studies on diet-delivered RNAi and their effects are summarized and followed by a discussion on the factors and hurdles affecting the efficacy of diet-delivered RNAi in H. armigera. PMID- 26549128 TI - High duty cycle pulses suppress orientation flights of crambid moths. AB - Bat-and-moth is a good model system for understanding predator-prey interactions resulting from interspecific coevolution. Night-flying insects have been under predation pressure from echolocating bats for 65Myr, pressuring vulnerable moths to evolve ultrasound detection and evasive maneuvers as counter tactics. Past studies of defensive behaviors against attacking bats have been biased toward noctuoid moth responses to short duration pulses of low-duty-cycle (LDC) bat calls. Depending on the region, however, moths have been exposed to predation pressure from high-duty-cycle (HDC) bats as well. Here, we reveal that long duration pulse of the sympatric HDC bat (e.g., greater horseshoe bat) is easily detected by the auditory nerve of Japanese crambid moths (yellow peach moth and Asian corn borer) and suppress both mate-finding flights of virgin males and host finding flights of mated females. The hearing sensitivities for the duration of pulse stimuli significantly dropped non-linearly in both the two moth species as the pulse duration shortened. These hearing properties support the energy integrator model; however, the threshold reduction per doubling the duration has slightly larger than those of other moth species hitherto reported. And also, Asian corn borer showed a lower auditory sensitivity and a lower flight suppression to short duration pulse than yellow peach moth did. Therefore, flight disruption of moth might be more frequently achieved by the pulse structure of HDC calls. The combination of long pulses and inter-pulse intervals, which moths can readily continue detecting, will be useful for repelling moth pests. PMID- 26549129 TI - Sex-pairing pheromone of Ancistrotermes dimorphus (Isoptera: Macrotermitinae). AB - Ancistrotermes dimorphus is a common Macrotermitinae representative, facultative inquiline by its life-style, occurring in South-East China. Sex pheromone is used for couple formation and maintenance, and it is produced by and released from the female sternal gland and is highly attractive to males. Based on our combined behavioral, chemical and electrophysiological analyses, we identified (3Z,6Z) dodeca-3,6-dien-1-ol as the female sex pheromone of A. dimorphus as it evoked the tandem behavior at short distance, and the active quantities ranged from 0.01ng to 10ng. Interestingly, GC-MS analyses of SPME extracts showed another compound specific to the female sternal gland, (3Z)-dodec-3-en-1-ol, which showed a clear GC-EAD response. However, this compound has no behavioral function in natural concentrations (0.1ng), while higher amounts (1ng) inhibit the attraction achieved by (3Z,6Z)-dodeca-3,6-dien-1-ol. The function of (3Z)-dodec-3-en-1-ol is not fully understood, but might be linked to recognition from sympatric species using the same major compound, enhancing the long-distance attraction, or informing about presence of other colonies using the compound as a trail following pheromone. The sternal gland secretion of Ancistrotermes females contains additional candidate compounds, namely (3E,6Z)-dodeca-3,6-dien-1-ol and (6Z)-dodec-6-en-1-ol, which are not perceived by males' antennae in biologically relevant amounts. PMID- 26549130 TI - Transcriptional and posttranscriptional regulation of cyanobacterial photosynthesis. AB - Cyanobacteria are well established model organisms for the study of oxygenic photosynthesis, nitrogen metabolism, toxin biosynthesis, and salt acclimation. However, in comparison to other model bacteria little is known about regulatory networks, which allow cyanobacteria to acclimate to changing environmental conditions. The current work has begun to illuminate how transcription factors modulate expression of different photosynthetic regulons. During the past few years, the research on other regulatory principles like RNA-based regulation showed the importance of non-protein regulators for bacterial lifestyle. Investigations on modulation of photosynthetic components should elucidate the contributions of all factors within the context of a larger regulatory network. Here, we focus on regulation of photosynthetic processes including transcriptional and posttranscriptional mechanisms, citing examples from a limited number of cyanobacterial species. Though, the general idea holds true for most species, important differences exist between various organisms, illustrating diversity of acclimation strategies in the very heterogeneous cyanobacterial clade. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof Conrad Mullineaux. PMID- 26549131 TI - Comparison of distortion product otoacoustic emissions and pure tone audiometry in occupational screening for auditory deficit due to noise exposure. AB - OBJECTIVE: To examine whether distortion product otoacoustic emissions can serve as a replacement for pure tone audiometry in longitudinal screening for occupational noise exposure related auditory deficit. METHODS: A retrospective review was conducted of pure tone audiometry and distortion product otoacoustic emission data obtained sequentially during mandatory screening of brickyard workers (n = 16). Individual pure tone audiometry thresholds were compared with distortion product otoacoustic emission amplitudes, and a correlation of these measurements was conducted. RESULTS: Pure tone audiometry threshold elevation was identified in 13 out of 16 workers. When distortion product otoacoustic emission amplitudes were compared with pure tone audiometry thresholds at matched frequencies, no evidence of a robust relationship was apparent. Seven out of 16 workers had substantial distortion product otoacoustic emissions with elevated pure tone audiometry thresholds. CONCLUSION: No clinically relevant predictive relationship between distortion product otoacoustic emission amplitude and pure tone audiometry threshold was apparent. These results do not support the replacement of pure tone audiometry with distortion product otoacoustic emissions in screening. Distortion product otoacoustic emissions at frequencies associated with elevated pure tone audiometry thresholds are evidence of intact outer hair cell function, suggesting that sites distinct from these contribute to auditory deficit following ototrauma. PMID- 26549133 TI - Inhibition of the expression of aquaporin-1 by RNA interference in pulmonary epithelial cells and its effects on water transport. AB - In the present study, the effect of aquaporin-1 (AQP1) on fluid transportation in pulmonary epithelial cells, and the role of AQP1 in alveolar fluid clearance were investigated to provide an experimental foundation to elucidate the pathogenesis of hyperoxic lung edema. An siRNA transfection technique was used to silence AQP1 in the A549 cell line. The transfected cells were randomized into a hyperoxia exposure and an air control group, with a negative control group set for each group. Cell volume was determined using flow cytometry, and Pf values were used to determine osmotic water permeability. Cell volume was found to be reduced in the AQP1-silenced A549 cells, compared with the negative control group 72 h following air exposure. In addition, cell volume was reduced in the AQP1-silenced A549 cells, compared with the negative control group 48 and 72 h following hyperoxia exposure. The osmotic water permeability of the AQP1-silenced cells was reduced in the air control and hyperoxia exposure groups, compared with the negative control group 48 and 72 h following exposure. The volume and cell membrane osmotic water permeability of the A549 cells were reduced, compared with those in the control group following AQP1-silencing, which indicated that the downregulation of AQP1 impedes extracellular to intracellular fluid transportation. Therefore, the disturbance in alveolar fluid clearance resulting from the downregulation of AQP1 following hyperoxia exposure may be one of the key mechanisms responsible for hyperoxic lung edema. PMID- 26549132 TI - Racism in the form of micro aggressions and the risk of preterm birth among black women. AB - PURPOSE: This study sought to examine whether perceived interpersonal racism in the form of racial micro aggressions was associated with preterm birth (PTB) and whether the presence of depressive symptoms and perceived stress modified the association. METHODS: Data stem from a cohort of 1410 black women residing in Metropolitan Detroit, Michigan, enrolled into the Life-course Influences on Fetal Environments (LIFE) study. The Daily Life Experiences of Racism and Bother (DLE B) scale measured the frequency and perceived stressfulness of racial micro aggressions experienced during the past year. Severe past-week depressive symptomatology was measured by the Centers for Epidemiologic Studies-Depression scale (CES-D) dichotomized at >= 23. Restricted cubic splines were used to model nonlinearity between perceived racism and PTB. We used the Perceived Stress Scale to assess general stress perceptions. RESULTS: Stratified spline regression analysis demonstrated that among those with severe depressive symptoms, perceived racism was not associated with PTB. However, perceived racism was significantly associated with PTB among women with mild to moderate (CES-D score <= 22) depressive symptoms. Perceived racism was not associated with PTB among women with or without high amounts of perceived stress. CONCLUSIONS: Our findings suggest that racism, at least in the form of racial micro aggressions, may not further impact a group already at high risk for PTB (those with severe depressive symptoms), but may increase the risk of PTB for women at lower baseline risk. PMID- 26549135 TI - Cauda equina syndrome after vertebroplasty. PMID- 26549134 TI - Infraorbital and infratrochlear nerve blocks combined with general anaesthesia for outpatient rhinoseptoplasty: A prospective randomised, double-blind, placebo controlled study. AB - INTRODUCTION: We conducted a study to determine the efficacy of bilateral extraoral infraorbital and infratrochlear nerve blocks during outpatient rhinoseptoplasty under general anaesthesia. PATIENTS AND METHODS: In this prospective, double-blind, randomised, controlled trial, 40 adult patients undergoing outpatient rhinoseptoplasty under general anaesthesia were assigned to receive bilateral infraorbital and infratrochlear nerve blocks with either 10mL of 0.25% levobupivacaine (Group LB) or isotonic saline (control group). Patients in Group LB received 0.1mL/kg of isotonic saline as a placebo and patients in the control group received 0.1mL/kg of morphine. The primary endpoint was total perioperative morphine consumption (intraoperative and in the post-anaesthesia care unit). The secondary endpoints were pain scores, time spent in the post anaesthesia care unit and the outpatient ward, block-related complications and patient satisfaction. RESULTS: The total dose of perioperative morphine was lower in Group LB than in the control group (2.5+/-2.8mg versus 9.5+/-3.5mg, respectively, P<0.001). The mean+/-SD or median [IQR] times spent in the post anaesthesia care unit (60+/-10min and 78+/-33min, respectively, P<0.03) and in the outpatient ward (210 [178-223] min versus 275 [250-300] min, respectively, P<0.001) were lower in Group LB than in the control group. There were no differences between groups for other endpoints. CONCLUSION: Bilateral extraoral infraorbital and infratrochlear nerve blocks performed with 0.25% levobupivacaine during general anaesthesia combining remifentanil and desflurane reduce the perioperative dose of morphine and the time spent in the post-anaesthesia care unit and the outpatient ward in adult patients undergoing outpatient rhinoseptoplasty. PMID- 26549136 TI - Erdheim-Chester disease in thoracic spine: a rare case of compression fracture. PMID- 26549137 TI - [Multimodal imaging of angle closure secondary to spherophakia in Weill Marchesani syndrome]. PMID- 26549138 TI - [Retinal perforation by a hard silicone buckle 20 years after retinal detachment surgery with an encircling buckle]. PMID- 26549139 TI - Idiopathic central retinal artery occlusion in an eight-year-old girl. PMID- 26549140 TI - [Aseptic serous cellulitis of the right hemiface following a retrobulbar alcohol injection]. PMID- 26549141 TI - [Safety of the automated microkeratome for Sub-Bowman's Keratomileusis on the flat cornea]. AB - INTRODUCTION: Use of the One Use-Plus SBK (Sub-Bowman's Keratomileusis) automated microkeratome (Moria, Antony, France) has been shown to be safe, predictable and comfortable for the creation of thin corneal flaps with a smooth and regular stromal bed. PURPOSE: To evaluate the use of the Moria One Use-Plus SBK (Moria, Antony, France) automated microkeratome on corneas with 180 degrees -keratometry under 40 diopters (D). METHODS: We retrospectively studied cases that underwent SBK whose 180 degrees -keratometry was under 40 D. We separated the cases between 39 and 40 D and those less than 39 D. The preoperative data, the procedure and the postoperative outcomes were analyzed. The Moria One Use-Plus SBK microkeratome with the 90-micron head was used for all cases. RESULTS: Among the 2883 eyes that underwent SBK LASIK over the past six years, 80 eyes (2.77%) had a preoperative topographical 180 degrees -keratometry of less than 40 D: 63 eyes (2.19%) between 39 and 40 D and 17 eyes (0.59%) between 38 and 39 D (38.13-38.97 D). The spherical equivalent was between -3.50 D (-2.25 sph -2.50 cyl. at 175 degrees ) and+6.00 D (+5.50 sph +1.00 cyl. at 85 degrees ). Fifty-eight eyes (72.5%) had hyperopia and/or hyperopic astigmatism; 18 eyes (22.5%) had mixed astigmatism; and 4 eyes (5%) had myopia and/or myopic astigmatism. Twenty-six eyes (32%) had a history of strabismus. Thirteen patients (27.66%) had a history of amblyopia. The "-1" ring was used in all cases, with a 7.5 stop (14%) or 8 stop (86%). The procedure went uneventfully in all cases with a stable vacuum between 117 and 123 mm Hg. The nasal hinge and the stromal bed were normal in size in all cases and sufficient to perform the photoablation laser safely with an optical zone between 6.00 and 7.00 millimeters. There were no intraoperative nor immediate postoperative complications: free cap 0%; incomplete flap 0%; button hole 0%; epithelial erosion 0%; bleeding 0%; irregular stromal bed 0%. Postoperative complications: flap displacement 0%; punctate keratitis: 8%; LASIK retreatments: 12%; safety: 100% (no loss of lines of visual acuity). DISCUSSION: Corneas with a topographical 180 degrees -keratometry under 40 D are a very small percentage of the total eyes that undergo LASIK (SBK). Those with a 180 degrees keratometry under 39 D are even more infrequent. Due to the characteristics of the flat cornea, the percentage of hyperopia is much larger in than in the general LASIK group. In addition, the percentage with a history of strabismus and amblyopia is higher. CONCLUSION: The Moria One Use-Plus SBK microkeratome is an excellent device that allows the easy creation of thin corneal flaps and regular and smooth corneal beds, safely and predictably even in extremely flat corneas without complications. The safety, efficacy and predictability are quite comparable to the general LASIK group. PMID- 26549142 TI - Thioiminium and thiaphospholanium derived from acetonitrile via nickel(II)-(2 mercaptophenyl)phosphine complexation. AB - [Ni(P(o-C6H4S)(o-C6H4SC(CH3)=NH2)(C6H5))2](ClO4)2 (2) with two thioiminium functionalities is derived from CH3CN solvent under anhydrous conditions. Moreover, thiaphospholanium salts, [(C6H5)P(C6H4SC(CH3)(NHCOCH3))(o C6H4SH)](ClO4) (3) and [(C6H5)2-P(C6H4SC(CH3)(NH3))](ClO4)2 (5), can be obtained through a similar Pinner-type nitrile activation. These results demonstrate the possible intermediate of enzymatic nitrile transformation and also provide an approach to the preparation of 2-amino-1,3-benzothiaphospholanium derivatives. PMID- 26549143 TI - [Subcutaneous nodules involving the forearms]. PMID- 26549144 TI - ASCO update on breast cancer, 2015. PMID- 26549145 TI - Chemical and structural modifications of RNAi therapeutics. AB - Small interfering RNA (siRNA), a 21-23nt double-stranded RNA responsible for post transcriptional gene silencing, has attracted great interests as promising genomic drugs, due to its strong ability to silence target genes in a sequence specific manner. Despite high silencing efficiency and on-target specificity, the clinical translation of siRNA has been hindered by its inherent features: poor intracellular delivery, limited blood stability, unpredictable immune responses and unwanted off-targeting effects. To overcome these hindrances, researchers have made various advances to modify siRNA itself and to improve its delivery. In this review paper, first we briefly discuss the innate properties and delivery barriers of siRNA. Then, we describe recent progress in (1) chemically and structurally modified siRNAs to solve their intrinsic problems and (2) siRNA delivery formulations including siRNA conjugates, polymerized siRNA, and nucleic acid-based nanoparticles to improve in vivo delivery. PMID- 26549146 TI - Safety-I, Safety-II and Resilience Engineering. AB - In the quest to continually improve the health care delivered to patients, it is important to understand "what went wrong," also known as Safety-I, when there are undesired outcomes, but it is also important to understand, and optimize "what went right," also known as Safety-II. The difference between Safety-I and Safety II are philosophical as well as pragmatic. Improving health care delivery involves understanding that health care delivery is a complex adaptive system; components of that system impact, and are impacted by, the actions of other components of the system. Challenges to optimal care include regular, irregular and unexampled threats. This article addresses the dangers of brittleness and miscalibration, as well as the value of adaptive capacity and margin. These qualities can, respectively, detract from or contribute to the emergence of organizational resilience. Resilience is characterized by the ability to monitor, react, anticipate, and learn. Finally, this article celebrates the importance of humans, who make use of system capabilities and proactively mitigate the effects of system limitations to contribute to successful outcomes. PMID- 26549148 TI - Dispatches from the International Behavioral Neuroscience Society meeting 2014. Introduction. AB - The International Behavioral Neuroscience Society (IBNS) was founded in 1992 to fill the need for a focused meeting of the international research community to discuss issues important for the development and progress of this scientific discipline. In the 20 plus years since its founding, IBNS has become a hub for the dissemination of new research, development of important research collaborations, support and networking for young investigators, and for outreach and education to the community. This work is covered in part by offering special sessions during the meeting for late-breaking scientific discoveries from a range of disciplines as well as background and seniority level of the presenters. This special issue is a culmination of the late-breaking research presented at the IBNS 2014 meeting. The manuscripts of this Special Issue cover a variety of themes, including, stress, depression, the intersection of monoamine systems and behavior, substance use disorders, attentional processes, and awareness and acceptance of brain training. This wide range of topics and interest as well as range in seniority of presenters demonstrate the driving interest of IBNS in advancing knowledge in behavioral neuroscience as well as supporting scientists at every level. PMID- 26549147 TI - Transient traumatic isolated neurogenic ptosis after a mild head trauma: a case report. AB - BACKGROUND: Transient traumatic isolated neurogenic ptosis (TTINP) is a sporadically reported rare entity. However, to the best of our knowledge, nearly all the reported cases are either secondary to direct periorbital trauma or surgery. We would like to report on a case of TTINP with countre-coup injury of the periorbital region. CASE PRESENTATION: A 49-year-old female slipped and fell down while walking. She was hospitalized with a moderate headache and undisturbed mental state. The patient recalled that the force bearing point was her occipital region. Physical examination and computed tomography (CT) on admission showed right isolated ptosis and mild contusion and laceration in the bilateral frontal cortex. Further radiological investigation revealed nothing remarkable except for a fracture of the superior portion of the right medial orbital wall. She was managed conservatively and recovered completely in two months. CONCLUSION: TTINP might manifest as a unique entity with a relatively mild, reversible, and non devastating injury to the terminal branch of the oculomotor nerve and for which perhaps no special treatment is needed. The proposed mechanism is injury of the terminal branch of the superior division of the oculomotor nerve. PMID- 26549149 TI - Activation of MEK/ERK pathways through NF-kappaB activation is involved in interleukin-1beta-induced cyclooxygenease-2 expression in canine dermal fibroblasts. AB - The proinflammatory cytokine interleukin-1beta (IL-1beta) induced cyclooxygenases 2 (COX-2) mRNA expression and lipid mediator prostaglandin E2 release and in a time- and dose-dependent manner in canine dermal fibroblasts. The MEK inhibitor U0126 and the ERK inhibitor FR180204 clearly inhibited IL-1beta-induced prostaglandin E2 release and COX-2 mRNA expression. IL-1beta enhanced ERK1/2 phosphorylation, which was attenuated by inhibitors of MEK and ERK. The NF-kappaB inhibitor BAY 11-7082 also suppressed IL-1beta-induced prostaglandin E2 release and COX-2 mRNA expression. Treatment of fibroblasts with IL-1beta led to the phosphorylation of p65 and degradation of IkappaBalpha occurred, indicating that IL-1beta treatment activated NF-kappaB. MEK and ERK1/2 inhibitors had no effect on the phosphorylation of p65 subunit induced by IL-1beta, whereas the NF-kappaB inhibitor completely blocked IL-1beta-induced phosphorylation of ERK1/2. We also observed that IkappaBalpha-knockdown enhanced the phosphorylation of p65 and ERK1/2. These findings suggest that stimulation of MEK/ERK signaling pathway by NF-kappaB activation regulates IL-1beta-induced COX-2 expression and subsequent prostaglandin E2 release in canine dermal fibroblasts. PMID- 26549150 TI - Re: 'Management of Extracranial Carotid Artery Aneurysm'. PMID- 26549151 TI - Effects of monetary reward and punishment on information checking behaviour. AB - Two experiments were conducted to examine whether checking one's own work can be motivated by monetary reward and punishment. Participants were randomly assigned to one of three conditions: a flat-rate payment for completing the task (Control); payment increased for error-free performance (Reward); payment decreased for error performance (Punishment). Experiment 1 (N = 90) was conducted with liberal arts students, using a general data-entry task. Experiment 2 (N = 90) replicated Experiment 1 with clinical students and a safety-critical 'cover story' for the task. In both studies, Reward and Punishment resulted in significantly fewer errors, more frequent and longer checking, than Control. No such differences were obtained between the Reward and Punishment conditions. It is concluded that error consequences in terms of monetary reward and punishment can result in more accurate task performance and more rigorous checking behaviour than errors without consequences. However, whether punishment is more effective than reward, or vice versa, remains inconclusive. PMID- 26549152 TI - [Why is it important to achieve the goals of treatment of hypertension.... About a case that began as ischemic stroke]. AB - Systemic arterial hypertension (SAH) is one of the most common conditions seen in primary care of cardiovascular disease and whose consequences; depending on the "target organ" affecting produce ischemic heart disease, cerebral vascular disease or chronic kidney disease. In the pathogenesis of HAS are several physiopathological mechanisms involved; of which currently, to name the most important and frequent play a role in increasing adrenaline levels, the renin angiotensin-aldosterone system and recently, much the participation of insulin resistance and hyperinsulinemia mentioned. These processes lead to an imbalance between the sympathetic and parasympathetic tone, coupled with hypersensitivity sodium trigger one of the pathophysiologic mechanisms of hypertension. SAH is currently defined as finding numbers of older blood pressure 140/90mm Hg. This is one of the diseases that most affect the world population prevalences found in age and gender groups 45 to 55% in men between 45 and 70 years and 45 to 65% in women of the same age group. In 2013 most recent clinical guidelines for treatment and the recommended goals, which has managed to reduce its complications and mortality were published; among which include vascular diseases such as ischemic heart and brain and kidney. In this paper a case that exemplifies the secondary complications in late diagnosis, damage to "target organ" by long-term exposure and inadequate compliance with therapeutic goals discussed. PMID- 26549153 TI - [Biatrial vs. isolated left atrial cryoablation for the treatment of long-lasting permanent atrial fibrillation. Midterm recurrence rate]. AB - The long-term results of cryomaze in patients with longstanding persistent atrial fibrillation during concomitant surgical procedures are still uncertain. METHODS: Between 2006 and 2011, 150 consecutive patients with associated long-lasting permanent atrial fibrillation and associated heart disease underwent heart surgery were treated by biatrial Cox-Maze (63 patients) or by isolated endocardial or epicardial left atrial cryoablation (83 patients) concomitantly. The results at 3 years in these groups were compared with clinical monitoring, electrocardiography, 24-hour Holter, and echocardiography with measurement of the transmitral A wave at 1, 6 and 12 months and annually thereafter in all patients. RESULTS: Patients undergoing Cox-Maze IV ablation presented rates of freedom from atrial fibrillation of 97, 94, 89, 80 and 54% at 1, 6, 12, 24 and 36 months, respectively. In the 12-month follow-up, these differences were significant (p<.05). The independent risk factors of atrial fibrillation recurrence was isolated ablation of left atrium. CONCLUSIONS: Atrial fibrillation by cryothermia ablation had a high success rate before 2 years postoperatively. Recurrence of atrial fibrillation increased thereafter regardless of the technique used, although it was more intense and developed earlier in cases of monoatrial ablation. For the treatment of other long-lasting permanent atrial fibrillation cardiac surgery-associated pathology, an aggressive biatrial treatment with Cox maze ablation should be performed. PMID- 26549154 TI - [The beginning of Mexican cardiology in the springtime of the Mexican National Academy of Medicine]. AB - The National Academy of Medicine was founded 141 years ago during the French intervention. Under the sponsorship of this brand-new medical association, Mexican cardioangiology took its first steps in the medical and surgical field as well. After the falling of the second empire, the medical and surgical advances of this discipline continued. The corresponding publications appeared in different volumes of the "Gaceta Medica de Mexico"; at present journal of the Academy still published in our time. These steps permitted the development of the true cardiologic speciality during 40s of the twentieth century, due to the vision of Professor Ignacio Chavez, father of Mexican cardiology. Some examples of application are the epistemologic criteria in cardiologycal domains such as the conception of Riva-Rocci's sphygmomanometer in Italy in the nineteenth century and the so-called cardiac metabolic therapy in Mexico of our time, are included. PMID- 26549155 TI - Predicting State Investment in Medicaid Home- and Community-Based Services, 2000 2011. AB - Although state use of Medicaid home- and community-based services (HCBS) to provide long-term services and supports to older adults and individuals with physical disabilities continues to increase, progress is uneven across states. We used generalized linear models to examine state factors associated with increased allocation of Medicaid dollars to HCBS for the period 2000 to 2011. We observed enhanced growth in states that began the period with limited investment in HCBS, as reflected in significant year trends among these states. The political environment appeared to be an important influence on states' investment for states with limited initial allocation to HCBS, as was housing affordability, a policy amenable variable. There continues to be wide variation in states' relative investment, calling for additional policy attention and research. PMID- 26549156 TI - Shifts Toward Morningness During Behavioral Sleep Interventions Are Associated With Improvements in Depression, Positive Affect, and Sleep Quality. AB - Morningness-eveningness (M-E) is typically considered to be a trait-like construct. However, M-E could plausibly shift in concert with changes in circadian or homeostatic processes. We examined M-E changes across three studies employing behavioral or pharmacological sleep treatments. Baseline and posttreatment M-E scores were strongly correlated across all three samples. M-E showed small but systematic changes toward morningness in sleep-disturbed military veterans receiving behavioral interventions. No systematic M-E changes were observed in the two pharmacological studies (sleep-disturbed military veterans and adults with primary insomnia, respectively). In the behavioral study, M-E changes correlated with changes in depression, positive affect, and sleep quality. M-E changes also correlated with changes in positive affect in the adult insomnia group. M-E appears to exhibit state-like aspects in addition to trait-like aspects. PMID- 26549157 TI - Antimullerian hormone: correlation with age and androgenic and metabolic factors in women from birth to postmenopause. AB - OBJECTIVE: To study the age-specific distribution of antimullerian hormone (AMH) and describe the association of AMH with androgenic and metabolic profiles at different ages. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 6,763 Chinese women from birth to menopause. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Anthropometric parameters (height, weight, and blood pressure), and levels of AMH and testosterone, glucose metabolism, and lipid profiles. RESULT(S): According to the level of AMH, four age phases were established: childhood (0-10 years), adolescence (11-18 years), reproductive age (19-50 years), and advanced age (>=51 years). During childhood and adolescence, AMH levels increased, reaching a peak at 18 years. A decline occurred thereafter during the reproductive-age period until the age of 50 years, and it remained at a low level above 0 onward. We found that AMH was negatively correlated with testosterone in childhood (r = -0.25), but was positively correlated with testosterone and the free androgen index in adolescence (r = 0.30; r = 0.26, respectively) as well as during the reproductive phases (r = 0.28; r = 0.31, respectively). No correlation was observed between AMH and body mass index, fasting blood glucose, fasting insulin, the homeostasis model assessment, total cholesterol, triglycerides, low-density lipoprotein, or high density lipoprotein at any phase. CONCLUSION(S): From birth to 18 years, AMH increases, then it declines thereafter, indicating changes of ovarian maintenance. A positive relationship between androgenic profiles and AMH during adolescence and reproductive years implies a synchronism between androgens and ovarian reserve. PMID- 26549159 TI - Race, Coping Style, and Substance Use Disorder Among Non-Hispanic African American and White Young Adults in South Florida. AB - BACKGROUND: Despite their higher rates of stress, African American young adults tend toward similar or lower rates of substance misuse than their White counterparts. Arguably, such patterns derive from: (1) racial variations in the availability of coping strategies that mitigate stress; and/or (2) racial differences in the efficacy of available coping styles for reducing substance misuse. OBJECTIVES: We assessed whether two coping style types-problem-focused and avoidance-oriented-varied by race (non-Hispanic African American vs. non Hispanic White) and whether the effects of coping styles on substance misuse were moderated by race. METHODS: Using data from a community sample of South Florida young adults, we employed logistic regression analyses to examine racial differences in coping style and to test if race by coping style interactions (race * problem-focused coping and race * avoidance-oriented coping) influenced the odds of qualifying for a DSM-IV substance use disorder, net of lifetime stressful events and sociodemographic controls. RESULTS: We found that African American young adults displayed lower problem-focused coping, and higher avoidance-oriented coping, than did White young adults. Among both African American and White respondents, problem-focused coping was associated with reduced odds of illicit drug use disorder (excluding marijuana), and among Whites, avoidance-oriented coping was associated with increased odds of an aggregate measure of alcohol, marijuana, and other illicit drug use disorders. Among African Americans, however, avoidance-oriented coping was associated with lower odds of marijuana use disorder. CONCLUSION: Substance misuse policies and practices that consider the sociocultural contexts of stress and coping are recommended. PMID- 26549158 TI - Dizziness, but not falls rate, improves after routine cataract surgery: the role of refractive and spectacle changes. AB - PURPOSE: To determine whether dizziness and falls rates change due to routine cataract surgery and to determine the influence of spectacle type and refractive factors. METHODS: Self-reported dizziness and falls were determined in 287 patients (mean age of 76.5 +/- 6.3 years, 55% females) before and after routine cataract surgery for the first (81, 28%), second (109, 38%) and both eyes (97, 34%). Dizziness was determined using the short-form of the Dizziness Handicap Inventory. Six-month falls rates were determined using self-reported retrospective data. RESULTS: The number of patients with dizziness reduced significantly after cataract surgery (52% vs 38%; chi(2) = 19.14(,) p < 0.001), but the reduction in the number of patients who fell in the 6-months post surgery was not significant (23% vs 20%; chi(2) = 0.87, p = 0.35). Dizziness improved after first eye surgery (49% vs 33%, p = 0.01) and surgery on both eyes (58% vs 35%, p < 0.001), but not after second eye surgery (52% vs 45%, p = 0.68). Multivariate logistic regression analyses found significant links between post operative falls and change in spectacle type (increased risk if switched into multifocal spectacles). Post-operative dizziness was associated with changes in best eye visual acuity and changes in oblique astigmatic correction. CONCLUSIONS: Dizziness is significantly reduced by first (or both) eye cataract surgery and this is linked with improvements in best eye visual acuity, although changes in oblique astigmatic correction increased dizziness. The lack of improvement in falls rate may be associated with switching into multifocal spectacle wear after surgery. PMID- 26549160 TI - Association between body composition and disease activity in rheumatoid arthritis. A systematic review. AB - BACKGROUND: Reports regarding the association between body composition and inflammatory activity in rheumatoid arthritis (RA) have consistently yielded contradictory results. OBJECTIVE: To perform a systematic review on the association between overweight/obesity and inflammatory activity in RA. METHODS: FAST approach: Article search (Medline, EBSCO, Cochrane Library), followed by abstract retrieval, full text review and blinded assessment of methodological quality for final inclusion. Because of marked heterogeneity in statistical approach and RA activity assessment method, a meta-analysis could not be done. Results are presented as qualitative synthesis. RESULTS: One hundred and nineteen reports were found, 16 of them qualified for full text review. Eleven studies (8,147 patients; n range: 37-5,161) approved the methodological quality filter and were finally included. Interobserver agreement for methodological quality score (ICC: 0.93; 95% CI: 0.82-0.98; P<.001) and inclusion/rejection decision (k 1.00, P>.001) was excellent. In all reports body composition was assessed by BMI; however a marked heterogeneity was found in the method used for RA activity assessment. A significant association between BMI and RA activity was found in 6 reports having larger mean sample size: 1,274 (range: 140-5,161). On the other hand, this association was not found in 5 studies having lower mean sample size: 100 (range: 7-150). CONCLUSIONS: The modulation of RA clinical status by body fat mass is suggested because a significant association was found between BMI and inflammatory activity in those reports with a trend toward higher statistical power. The relationship between body composition and clinical activity in RA requires be approached with further studies with higher methodological quality. PMID- 26549161 TI - Optimizing Clinical Research Participant Selection with Informatics. AB - Clinical research participants are often not reflective of real-world patients due to overly restrictive eligibility criteria. Meanwhile, unselected participants introduce confounding factors and reduce research efficiency. Biomedical informatics, especially Big Data increasingly made available from electronic health records, offers promising aids to optimize research participant selection through data-driven transparency. PMID- 26549162 TI - Dural Enhancement in a Patient with Sturge-Weber Syndrome Revealed by Double Inversion Recovery Contrast Using Synthetic MRI. PMID- 26549163 TI - Comparison of Gated and Ungated Black-Blood Fast Spin-echo MRI of Carotid Vessel Wall at 3T. AB - PURPOSE: Multi-slice ungated double inversion recovery has been proposed as an alternative time-efficient and effective sequence for black-blood carotid imaging. The purpose of this study is to evaluate the comparative repeatability of this multi-contrast sequence with respect to a single slice double inversion recovery prepared gated sequence. MATERIALS AND METHODS: Ten healthy volunteers and three patients with Doppler ultrasound defined carotid artery stenosis >30% were recruited. T1-weighted (T1W) and T2W fast spin-echo (FSE) images were acquired centered at the carotid bifurcation with and without cardiac gating. Repeat imaging was performed without patient repositioning to determine the variations in vessel wall measurement and signal intensity due to gating, while negating variations as a result of slice misalignment and anatomical displacement relative to the receiver coil. The distributions and the repeatability of lumen area, vessel wall area, signal and contrast-to-noise ratio (SNR/CNR) of the vessel wall and adjacent muscle were reported. RESULTS: The T1W ungated sequence generally had comparable wall SNR/CNR with respect to the gated sequence, however the muscle SNR was lower (P = 0.013). The T2W ungated multi-slice sequence had lower SNR/CNR than the gated single slice sequence (P < 0.001), but with equivalent effective wall CNR (P = 0.735). Vessel area measurements using the gated/ungated sequences were equivalent. Ungated sequences had better repeatability in SNR/CNR than the gated sequences with borderline and statistically significant differences. The repeatability of T2W wall area measurement was better using the ungated sequences (P = 0.02), and the repeatability of the remaining vessel area measurements were equivalent. CONCLUSIONS: Ungated sequences can achieve comparable SNR/CNR and equivalent carotid vessel area measurements than gated sequences with improved repeatability of SNR/CNR. Ungated sequences are good alternatives of gated sequences for vessel area measurement and plaque composition quantification. PMID- 26549164 TI - Quantitative Assessment of Head Motion toward Functional Magnetic Resonance Imaging during Stepping. AB - PURPOSE: Stepping motions have been often used as gait-like patterns in functional magnetic resonance imaging (fMRI) to understand gait control. However, it is still very difficult to stabilize the task-related head motion. Our main purpose is to provide characteristics of the task-related head motion during stepping to develop robust restraints toward fMRI. METHODS: Multidirectional head and knee position during stepping were acquired using a motion capture system outside MRI room in 13 healthy participants. Six phases in a stepping motion were defined by reference to the left knee angles and the mean of superior-inferior head velocity (Vmean) in each phase was investigated. Furthermore, the correlation between the standard deviation of the knee angle (thetasd) and the maximum of the head velocity (Vmax) was evaluated. RESULTS: The standard deviation of each superior-inferior head position and pitch were significantly larger than the other measurements. Vmean showed a characteristic repeating pattern associated with the knee angle. Additionally, there were significant correlations between thetasd and Vmax. CONCLUSIONS: This is the first report to reveal the characteristics of the task-related head motion during stepping. Our findings are an essential step in the development of robust restraint toward fMRI during stepping task. PMID- 26549165 TI - miR-296-5p suppresses cell viability by directly targeting PLK1 in non-small cell lung cancer. AB - Polo-like kinase 1 (PLK1), a critical kinase for mitotic progression, is overexpressed in a wide range of cancers. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules and proposed to play important roles in the regulation of tumor progression and invasion. However, the relationship between PLK1 and miRNAs have remained unclear. In the present study, the association between PLK1 and miR-296-5p was investigated. The upregulation of PLK1 mRNA expression levels combined with the downregulation of miR-296-5p levels were detected in both non small cell lung cancer (NSCLC) tissues and cell lines. Functional studies showed that knockdown of PLK1 by siRNA inhibited NSCLC cells proliferation. Impressively, overexpression of miR-296-5p showed the same phenocopy as the effect of PLK1 knockdown in NSCLC cells, indicating that PLK1 was a major target of miR-296-5p. Furthermore, using western blot analysis and luciferase reporter assay, PLK1 protein expression was proved to be regulated by miR-296-5p through binding to the putative binding sites in its 3'-untranslated region (3'-UTR). Taken together, the present study indicated that miR-296-5p regulated PLK1 expression and could function as a tumor suppressor in NSCLC progression, which provides a potential target for gene therapy of NSCLC. PMID- 26549166 TI - Photo-generated metamaterials induce modulation of CW terahertz quantum cascade lasers. AB - Periodic patterns of photo-excited carriers on a semiconductor surface profoundly modifies its effective permittivity, creating a stationary all-optical quasi metallic metamaterial. Intriguingly, one can tailor its artificial birefringence to modulate with unprecedented degrees of freedom both the amplitude and phase of a quantum cascade laser (QCL) subject to optical feedback from such an anisotropic reflector. Here, we conceive and devise a reconfigurable photo designed Terahertz (THz) modulator and exploit it in a proof-of-concept experiment to control the emission properties of THz QCLs. Photo-exciting sub wavelength metastructures on silicon, we induce polarization-dependent changes in the intra-cavity THz field, that can be probed by monitoring the voltage across the QCL terminals. This inherently flexible approach promises groundbreaking impact on THz photonics applications, including THz phase modulators, fast switches, and active hyperbolic media. PMID- 26549167 TI - An update on antimicrobial options for childhood community-acquired pneumonia: a critical appraisal of available evidence. AB - INTRODUCTION: Community-acquired pneumonia (CAP) is a leading cause of death and a major cause of morbidity in children under the age of 5. Appropriate antimicrobial use is one crucial tool in controlling childhood CAP mortality and suffering. AREAS COVERED: Structured search of current literature. PubMed was consulted for published trials conducted in children with CAP. We aimed to provide a comprehensive evaluation of antimicrobials used to treat childhood CAP, including a critical appraisal of the methodological aspects of these clinical trials. EXPERT OPINION: Amoxicillin is the preferred option to treat non-severe non-complicated CAP among children aged >=2 months. Amoxicillin may be used to treat children in this age group with severe CAP if they do not require hospital assistance. If the patient warrants hospitalization, intravenous penicillin is the chosen option. Heterogeneity was high in the included trials, in regard to clinical inclusion criteria, use of radiological inclusion criteria, placebo use and masking. Higher quality evidence was found in the studies which included amoxicillin. There is a clear dearth of randomized, placebo-controlled, well performed clinical trials evaluating children with CAP aged under 2 months, or aged 2 months and above with very severe or complicated CAP, or in specific age groups like teenagers. PMID- 26549168 TI - Road safety education: What works? AB - OBJECTIVES: The objectives of the paper are: METHOD: Seminal papers, collaborative reports from traffic safety research institutes and books from experts have been used as materials. Very diverse fields of application are presented such as: the importance of emotional experience in interaction with traffic experiences; the efficiency of e-learning; the efficiency of simulators to improve hazard perception skills and calibration of one's driving competencies; the efficiency of social norms marketing at changing behaviors by correcting normative misperceptions; the usefulness of parents-based interventions to improve parental supervision; and finally the importance of multi-components programs due to their synergies. CONCLUSIONS: Scientific evidence collected in this paper shows that RSE may have some positive effects if good practices are adopted, if it is part of a lifelong learning process and if transmits not only knowledge but also "life-skills" (or psycho-social competences). IMPLICATIONS: for practice From each example, we will see the implications of the results for the implementation of RSE. PMID- 26549169 TI - Choosing treatment and screening options congruent with values: Do decision aids help? Sub-analysis of a systematic review. AB - OBJECTIVE: To understand how well patients make value congruent decisions with and without patient decision aids (PtDAs) for screening and treatment options, and identify issues with its measurement and evaluation. METHODS: A sub-analysis of trials included in the 2014 Cochrane Review of Decision Aids. Eligible trials measured value congruence with chosen option. Two reviewers independently screened 115 trials. RESULTS: Among 18 included trials, 8 (44%) measured value congruence using the Multidimensional Measure of Informed Choice (MMIC), 7 (39%) used heterogeneous methods, and 3 (17%) used unclear methods. Pooled results of trials that used heterogeneous measures were statistically non-significant (n=3). Results from trials that used the MMIC suggest patients are 48% more likely to make value congruent decisions when exposed to a PtDA for a screening decision (RR 1.48, 95% CI 1.01 to 2.16, n=8). CONCLUSION: Patients struggle to make value congruent decisions, but PtDAs may help. While the absolute improvement is relatively small it may be underestimated due to sample size issues, definitions, and heterogeneity of measures. PRACTICE IMPLICATIONS: Current approaches are inadequate to support patients making decisions that are consistent with their values. There is some evidence that PtDAs support patients with achieving values congruent decisions for screening choices. PMID- 26549170 TI - Knowledge displays: Soliciting clients to fill knowledge gaps and to reconcile knowledge discrepancies in therapeutic interaction. AB - OBJECTIVE: To examine knowledge displays (KDs), a practice by which Therapeutic Community (TC) professionals exhibit previous knowledge about their clients' circumstances and experiences. METHODS: Conversation analysis is used to examine 12 staff-led meetings recorded in Italy (8 in a drug addiction TC; 4 in a mental health TC). RESULTS: The TC professionals use KDs within broader sequences of talk where they solicit their clients to share personal information and where the clients provide insufficient or inconsistent responses. In these circumstances, the staff members employ KDs to pursue responses that redress emerging knowledge gaps and discrepancies regarding the clients' experiences or circumstances. CONCLUSION: KDs allow the staff members to achieve a balance between respecting their clients' right to report their own experiences and influencing the ways in which they report them. KDs help to reinforce the culture of openness that is central to many forms of therapeutic interaction, to forward the therapeutic agenda and to expand the staff members' knowledge of the clients' experiences and circumstances. PRACTICE IMPLICATIONS: KDs can be used to solicit clients to share personal information. This paper illustrates core features that underlie the function of KDs (where they are used and how they are constructed). PMID- 26549171 TI - Social support and self-management capabilities in diabetes patients: An international observational study. AB - OBJECTIVE: The objective of this study was to explore which aspects of social networks are related to self-management capabilities and if these networks have the potential to reduce the adverse health effects of deprivation. METHODS: In a cross-sectional study we recruited type 2 diabetes patients in six European countries. Data on self-management capabilities was gathered through written questionnaires and data on social networks characteristics and social support through subsequent personal/telephone interviews. We used regression modelling to assess the effect of social support and education on self-management capabilities. RESULTS: In total 1692 respondents completed the questionnaire and the interview. Extensive informational networks, emotional networks, and attendance of community organisations were linked to better self-management capabilities. The association of self-management capabilities with informational support was especially strong in the low education group, whereas the association with emotional support was stronger in the high education group. CONCLUSION: Some of the social network characteristics showed a positive relation to self management capabilities. The effect of informational support was strongest in low education populations and may therefore provide a possibility to reduce the adverse impact of low education on self-management capabilities. PRACTICE IMPLICATIONS: Self-management support interventions that take informational support in patients' networks into account may be most effective, especially in deprived populations. PMID- 26549172 TI - Immunostimulation by phospholipopeptide biosurfactant from Staphylococcus hominis in Oreochromis mossambicus. AB - The immunostimulatory effect of phospholipopeptide biosurfactant from Staphylococcus hominis (GenBank Accession No: KJ564272) was assessed with Oreochromis mossambicus. The non-specific (serum lysozyme activity, serum antiprotease activity, serum peroxidase activity and serum bactericidal activity), specific (bacterial agglutination assay) immune responses and disease resistance activity against Aeromonas hydrophila were examined. Fish were intraperitonially injected with water soluble secondary metabolite (biosurfactant) of S. hominis at a dose of 2 mg, 20 mg and 200 mg kg(-1) body weight. Commercial surfactant surfactin (sigma) at 20 mg kg(-1) was used as standard and saline as negative control. All the doses of water soluble biosurfactant tested, significantly enhanced the specific, nonspecific immunity and disease resistance from the day of post administration of phospholipopeptide biosurfactant till the tail of the experimental period. These results clearly indicated that the secondary metabolite isolated from S. hominis stimulates the immunity of finfish thereby could enhance aquaculture production. PMID- 26549173 TI - A multivariate assessment of innate immune-related gene expressions due to exposure to low concentration individual and mixtures of four kinds of heavy metals on zebrafish (Danio rerio) embryos. AB - Concerns over the potential health effects of mixtures of low concentration heavy metals on living organisms keep growing by the day. However, the toxicity of low concentration metal mixtures on the immune system of fish species has rarely been investigated. In this study, the zebrafish model was employed to investigate the effect on innate immune and antioxidant-related gene expressions, on exposure to environmentally relevant concentrations of individual and mixtures of Pb (0.01 mg/L), Hg (0.001 mg/L), As (0.01 mg/L) and Cd (0.005 mg/L). Messenger-RNA (mRNA) levels of IL1beta, TNF-alpha, IFNgamma, Mx, Lyz, C3B and CXCL-Clc which are closely associated with the innate immune system were affected after exposing zebrafish embryos to metals for 120 h post fertilization (hpf). Individual and mixtures of metals exhibited different potentials to modulate innate-immune gene transcription. IL1beta genes were significantly up regulated on exposure to Pb + As (2.01-fold) and inhibited on exposure to Pb + Hg + Cd (0.13-fold). TNF-alpha was significantly inhibited on exposure to As (0.40-fold) and Pb + As (0.32-fold) compared to control. Metal mixtures generally up regulated IFNgamma compared to individual metals. Additionally, antioxidant genes were affected, as CAT and GPx gene expressions generally increased, whiles Mn-SOD and Zn/Cu-SOD reduced. Multivariate analysis showed that exposure to individual metals greatly influenced modulation of innate immune genes; whiles metal mixtures influenced antioxidant gene expressions. This suggests that beside oxidative stress, there may be other pathways influencing gene expressions of innate immune and antioxidant-related genes. Low concentration heavy metals also affect expression of development-related (wnt8a and vegf) genes. Altogether, the results of this study clearly demonstrate that low concentration individual and mixtures of metals in aquatic systems will greatly influence the immune system. It is indicative that mechanisms associated with toxicity of metal mixtures is complex, however, further studies to elucidate them are ongoing in our research laboratory. PMID- 26549174 TI - Molecular, genomic, and expressional delineation of a piscidin from rock bream (Oplegnathus fasciatus) with evidence for the potent antimicrobial activities of Of-Pis1 peptide. AB - The piscidin family comprises a group of antimicrobial peptides (AMPs) that are vital components of teleost innate immunity. Piscidins protect the host from pathogens, through multifaceted roles as immunomodulators and anti-infective peptides. The present study reports the identification, and characterization of a putative piscidin homolog, Of-Pis1, from rock bream (Oplegnathus fasciatus). A combined genomic and transcriptomic approach revealed that the Of-Pis1 gene comprises 1396 nucleotides (nt), four exons, and three introns. The cDNA with the 213 nt open reading frame encoded a 70-amino acid preprotein consisting of a signal peptide, a mature peptide, and a prodomain. Predicted mature Of-Pis1 was assumed to be a membrane-active AMP, based on the prediction of an amphipathic alpha-helical conformation with a net charge of +4. In addition, Of-Pis1 demonstrated significant similarities with other piscidin family members in terms of gene structure, sequence homology, and evolutionary relationship. Examination by quantitative real-time PCR (qPCR) of basal transcription of Of-Pis1 in the tissues of naive rock bream, revealed predominant transcript levels in the gills, followed by the spleen, intestine, skin, and head kidney. In gill tissues, the temporally induced mRNA expression of Of-Pis1, upon in vivo injection trials with lipopolysaccharide (LPS); polyinosinic:polycytidylic acid (poly I:C); and pathogens, including Edwardsiella tarda, Streptococcus iniae, and rock bream iridovirus (RBIV), was weak. In contrast, in vivo flagellin administration led to a robust upregulation of Of-Pis1 in different tissues. Antimicrobial potency was determined by employing recombinant (rOf-Pis1), and synthetic (pOf-Pis1) peptides, in in vitro assays. Recombinant overexpression inhibited the growth of bacteria expressing the rOf-Pis1 protein in a growth delay assay. The broad antimicrobial spectrum of pOf-Pis1 was evidenced by its potent activity against an array of microbes, including bacteria, fungi, and parasitic species. In addition, pOf-Pis1 showed no significant hemolytic toxicity against human erythrocytes. Collectively, the data presented in the current study improve our understanding of the piscidin AMP family, and the contribution of Of-Pis1 to the rock bream immunity. PMID- 26549175 TI - Cathepsin L is an immune-related protein in Pacific abalone (Haliotis discus hannai)--Purification and characterization. AB - Cathepsin L, an immune-related protein, was purified from the hepatopancreas of Pacific abalone (Haliotis discus hannai) by ammonium sulfate precipitation and column chromatographies of SP-Sepharose and Sephacryl S-200 HR. Purified cathepsin L appeared as two bands with molecular masses of 28.0 and 28.5 kDa (namely cathepsin La and Lb) on SDS-PAGE under reducing conditions, suggesting that it is a glycoprotein. Peptide mass fingerprinting (PMF) analysis revealed that peptide fragments of 95 amino acid residues was high similarity to cathepsin L of pearl oyster (Pinctada fucata). The optimal temperature and pH of cathepsin L were 35 degrees C and pH 5.5. Cathepsin L was particularly inhibited by cysteine proteinase inhibitors of E-64 and leupeptin, while it was activated by metalloproteinase inhibitors EDTA and EGTA. The full-length cathepsin L cDNA was further cloned from the hepatopancreas by rapid PCR amplification of cDNA ends (RACE). The open reading frame of the enzyme was 981 bp, encoding 327 amino acid residues, with a conserved catalytic triad (Cys134, His273 and Asn293), a potential N-glycosylation site and conserved ERFNIN, GNYD, and GCGG motifs, which are characteristics of cathepsin L. Western blot and proteinase activity analysis revealed that the expression and enzyme activity of cathepsin L were significantly up-regulated in hepatopancreas at 8 h following Vibrio parahaemolyticus infection, demonstrating that cathepsin L is involved in the innate immune system of abalone. Our present study for the first time reported the purification, characterization, molecular cloning, and tissue expression of cathepsin L in abalone. PMID- 26549176 TI - Increased stocking density causes changes in expression of selected stress- and immune-related genes, humoral innate immune parameters and stress responses of rainbow trout (Oncorhynchus mykiss). AB - The present study investigated the effects of various stocking densities on the health status (stress and immune responses) of rainbow trout (Onchorhynchus mykiss). Juvenile rainbow trout were acclimated, placed in circular tanks under stocking densities of 10, 40 and 80 kg m(-3) and reared for 30 days. The relative expression of genes involved in stress and immunity such as HSP70, LyzII, TNF 1alpha, IL-1beta, IL-8 and IFN-gamma1 in the head kidney was determined. Serum cortisol, ACTH, total antioxidant capacity, osmolality and lactate were measured after 30 days of culture at different stocking densities (D1:10 kg m(-3), D2: 40 kg m(-3) and D3: 80 kg m(-3)) as indices of stress responses. In addition, the effects of stocking densities on serum complement, bactericidal activity, agglutinating antibody titers, serum IgM, anti-protease activity, serum total protein and alkaline phosphatase of the fish were measured. HSP70 gene expression was significantly density-dependent upregulated in D2 and D3 densities compared to D1 (P < 0.05). Also, there was significant downregulation in expression of LyzII, TNF-1alpha, IL-1beta, IL-8 and IFN-gamma1 in fish reared at density of either D2 or D3 (P < 0.05). In terms of stress responses, serum ACTH, cortisol and lactate level showed significant density-dependent increase (P < 0.05) while serum osmolality and total antioxidant capacity showed significant decline (P < 0.05) in fish reared at higher densities (D2 and D3) compared to fish reared at lower density (D1) (P < 0.05). Concordant with the expression of the immune related genes, the serum complement and bactericidal activity as well as specific antibody titer against Aeromonas hydrophila, IgM and anti-protease activity decreased along with elevation of stocking density from D1 to D3 (P < 0.05). However, different stocking densities had no significant effect on serum total protein level and alkaline phosphatase activity. These results suggested that elevation of stocking densities and crowding resulted in the increase in HSP70 gene expression and the levels of selected stress responses in the serum. However, there was down-regulation of immune genes expression and decreased innate immune responses in the fish. The mRNA expression of the genes and immune parameters that were measured in this study could be helpful in monitoring the health status and welfare of the fish in aquaculture systems particularly in relation to increased stocking densities. PMID- 26549177 TI - Molecular cloning and characterization of orange-spotted grouper (Epinephelus coioides) CXC chemokine ligand 12. AB - Chemokines are a family of soluble peptides that can recruit a wide range of immune cells to sites of infection and disease. The CXCL12 is a chemokine that binds to its cognate receptor CXCR4 and thus involved in multiple physiological and pathophysiological processes. In this study, we cloned and characterized CXCL12 from Epinephelus coioides (osgCXCL12). We found that the open reading frame of osgCXCL12 consists of 98 amino acid residues with the small cytokine C-X C domain located between residues 29 and 87. Higher expression levels for osgCXCL12 were detected at the kitting stage, compared with the prolarva and larva shape stages. The expression patterns revealed that osgCXCL12 may play a key role in early grouper development. We detected mRNA transcripts for osgCXCL12 in healthy tissues and found the highest osgCXCL12 expression in the head kidney. Furthermore, a time-course analysis revealed significantly increased osgCXCL12 and osgCXCR4 expression levels after the nervous necrosis virus (NNV) challenge. In addition, expression of osgCXCL12 was affected by injection with microbial mimics [LPS and poly(I:C)]. These results suggest that osgCXCL12 is associated with inflammatory and developmental processes in the grouper. PMID- 26549178 TI - Pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimp. AB - Acute hepatopancreatic necrosis disease (AHPND), also called early mortality syndrome (EMS), is a recently emergent shrimp bacterial disease that has resulted in substantial economic losses since 2009. AHPND is known to be caused by strains of Vibrio parahaemolyticus that contain a unique virulence plasmid, but the pathology of the disease is still unclear. In this study, we show that AHPND causing strains of V. parahaemolyticus secrete the plasmid-encoded binary toxin PirAB(vp) into the culture medium. We further determined that, after shrimp were challenged with AHPND-causing bacteria, the bacteria initially colonized the stomach, where they started to produce PirAB(vp) toxin. At the same early time point (6 hpi), PirB(vp) toxin, but not PirA(vp) toxin, was detected in the hepatopancreas, and the characteristic histopathological signs of AHPND, including sloughing of the epithelial cells of the hepatopancreatic tubules, were also seen. Although some previous studies have found that both components of the binary PirAB(vp) toxin are necessary to induce a toxic effect, our present results are consistent with other studies which have suggested that PirB(vp) alone may be sufficient to cause cellular damage. At later time points, the bacteria and PirA(vp) and PirB(vp) toxins were all detected in the hepatopancreas. We also show that Raman spectroscopy "Whole organism fingerprints" were unable to distinguish between AHPND-causing and non-AHPND causing strains. Lastly, by using minimum inhibitory concentrations, we found that both virulent and non-virulent V. parahaemolyticus strains were resistant to several antibiotics, suggesting that the use of antibiotics in shrimp culture should be more strictly regulated. PMID- 26549179 TI - ChAkt1 involvement in orchestrating the immune and heat shock responses in Crassostrea hongkongensis: Molecular cloning and functional characterization. AB - G-protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors and play crucial roles in virtually every organ system. As one of the major downstream effectors of GPCRs, Akt can acquire information from the receptors and coordinate intracellular responses for many signaling pathways, through which the serine/threonine kinase masters numerous aspects of biological processes, such as cell survival, growth, proliferation, migration, angiogenesis, and metabolism. In the present study, we have characterized the first Akt1 ortholog in mollusks using the Hong Kong oyster, Crassostrea hongkongensis (designed ChAkt1). The full-length cDNA is 2223 bp and encodes a putative protein of 493 amino acids that contains an amino-terminal pleckstin homology (PH) domain, a central catalytic domain, and a carboxy-terminal regulatory domain. Quantitative real-time PCR analysis showed that ChAkt1 mRNA is broadly expressed in various tissues and during different stages of the oyster's embryonic and larval development. Upon exposure to two stressors (microbial infection and heat shock), the expression level of ChAkt1 mRNA increases significantly. Furthermore, ChAkt1 is located in the cytoplasm in HEK293T cells, where the over-expression of ChAkt1 regulates the transcriptional activities of NF-kappaB and p53 reporter genes. Taken together, our results indicate that ChAkt1 most likely plays a central role in response to various stimuli in oysters and has a particular response to microbial pathogens and high temperature. PMID- 26549180 TI - Feedback to semi-professional counselors in treating child aggression. AB - OBJECTIVE: To investigate the impact of outcome feedback provided to semi professional counselors of children and adolescents at risk for aggressive behavior, following group treatment. METHOD: Participants included 230 aggressive children and adolescents and 64 educators in a quasi-experimental design of 3 conditions: experimental group with feedback, experimental group without feedback, and control group (no treatment). The current study employed a feedback system based on self-report aggression scores measured after each session, provided to teachers, including an alert system and weekly follow-up group support. RESULTS: Outcomes were more favorable for the treatment children than the control group, but feedback had no impact on the results. CONCLUSION: Outcome feedback provided to group therapists does not have an effect on children and adolescents' reduction of aggression. Further research is needed to identify possible reasons for failure to show feedback effect. PMID- 26549181 TI - Targets to treat androgen excess in polycystic ovary syndrome. AB - INTRODUCTION: The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. AREAS COVERED: The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. EXPERT OPINION: PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects. PMID- 26549182 TI - Corrigendum. PMID- 26549184 TI - Filament formation of Salmonella Paratyphi A accompanied by FtsZ assembly impairment and low level ppGpp. AB - Previously, we reported that Salmonella enterica serovar Paratyphi A strain S602 grew into multinuclear, nonseptate, and nonlethal filaments on agar plates containing nitrogenous salts. Strain S602 was more sensitive to osmotic and oxidative stress than the reference strain 3P243 of nonfilamentous Salmonella Paratyphi A. Strain S602 had an amber mutation (C154T) in rpoS. The revertant of this mutant, SR603, was repressed to form filaments under conditions with abundant nitrogenous salts. However, 3PR244, an rpoS mutant of 3P243 (C154T), did not form filaments, which implies that the rpoS mutation is not the sole cause of filamentation in strain S602. Next, we examined whether the level of guanosine 5' diphosphate 3'-diphosphate (ppGpp) in S602 strain is involved in filament formation. The intracellular ppGpp level in filamentous cells was lower than that in nonfilamentous cells. Furthermore, cells belonging to strain RE606, a derivative of S602 where the intracellular concentration of ppGpp was increased by overexpression of the relA gene, exhibited normal Z-ring formation and cell division. In the S602 strain, the decrease in the ppGpp level induced by the presence of nitrogenous salt and the rpoS mutation led to the inhibition of Z ring formation and the subsequent filamentation of cells. PMID- 26549185 TI - Size does matter: 18 amino acids at the N-terminal tip of an amino acid transporter in Leishmania determine substrate specificity. AB - Long N-terminal tails of amino acid transporters are known to act as sensors of the internal pool of amino acids and as positive regulators of substrate flux rate. In this study we establish that N-termini of amino acid transporters can also determine substrate specificity. We show that due to alternative trans splicing, the human pathogen Leishmania naturally expresses two variants of the proline/alanine transporter, one 18 amino acid shorter than the other. We demonstrate that the longer variant (LdAAP24) translocates both proline and alanine, whereas the shorter variant (?18LdAAP24) translocates just proline. Remarkably, co-expressing the hydrophilic N-terminal peptide of the long variant with ?18LdAAP24 was found to recover alanine transport. This restoration of alanine transport could be mediated by a truncated N-terminal tail, though truncations exceeding half of the tail length were no longer functional. Taken together, the data indicate that the first 18 amino acids of the negatively charged N-terminal LdAAP24 tail are required for alanine transport and may facilitate the electrostatic interactions of the entire negatively charged N terminal tail with the positively charged internal loops in the transmembrane domain, as this mechanism has been shown to underlie regulation of substrate flux rate for other transporters. PMID- 26549186 TI - Reply to 'Adjusting for Ethnicity'. PMID- 26549187 TI - Development of suitable hydroponics system for phytoremediation of arsenic contaminated water using an arsenic hyperaccumulator plant Pteris vittata. AB - In this study, we found that high-performance hydroponics of arsenic hyperaccumulator fern Pteris vittata is possible without any mechanical aeration system, if rhizomes of the ferns are kept over the water surface level. It was also found that very low-nutrition condition is better for root elongation of P. vittata that is an important factor of the arsenic removal from contaminated water. By the non-aeration and low-nutrition hydroponics for four months, roots of P. vittata were elongated more than 500 mm. The results of arsenate phytofiltration experiments showed that arsenic concentrations in water declined from the initial concentrations (50 MUg/L, 500 MUg/L, and 1000 MUg/L) to lower than the detection limit (0.1 MUg/L) and about 80% of arsenic removed was accumulated in the fern fronds. The improved hydroponics method for P. vittata developed in this study enables low-cost phytoremediation of arsenic-contaminated water and high-affinity removal of arsenic from water. PMID- 26549188 TI - Nurses' Role in Cardiovascular Risk Assessment and Management in People with Inflammatory Arthritis: A European Perspective. AB - INTRODUCTION: Cardiovascular risk (CVR) assessment and management in patients with inflammatory arthritis (IA) is recommended but European nurses' involvement in this role has not been well studied. AIM: The aim of the present study was to explore European nurses' role in assessing and managing CVR, in order to suggest topics for practice development and research in this area regarding persons with IA. METHODS: We searched Embase, Cinahl, Cochrane, PsycInfo and PubMed databases and included European articles from the past ten years if they described how nurses assess and/or manage CVR. In addition to the systematic review, we provided case studies from five different countries to illustrate national guidelines and nurses' role regarding CVR assessment and management in patients with IA. RESULTS: Thirty-three articles were included. We found that trained nurses were undertaking CVR assessment and management in different settings and groups of patients. The assessments include blood pressure, body mass index, waist circumference, glucose and lipid-profile, adherence to medication and behavioural risk factors (unhealthy diet, physical inactivity, alcohol and smoking). Different tools were used to calculate patients' risk. Risk management differed from brief advice to long-term follow-up. Nurses tended to take a holistic and individually tailored approach. Clinical examples of inclusion of rheumatology nurses in these tasks were scarce. CONCLUSION: Nurses undertake CVR assessment, communication and management in different types of patients. This is considered to be a highly relevant task for rheumatology nursing, especially in patients with IA. Further studies are needed to assess patients' perspective, effectiveness and cost-effectiveness of nurse-led CVR. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549189 TI - A metabolomics study delineating geographical location-associated primary metabolic changes in the leaves of growing tobacco plants by GC-MS and CE-MS. AB - Ecological conditions and developmental senescence significantly affect the physiological metabolism of plants, yet relatively little is known about the influence of geographical location on dynamic changes in plant leaves during growth. Pseudotargeted gas chromatography-selected ion monitoring-mass spectrometry and capillary electrophoresis-mass spectrometry were used to investigate a time course of the metabolic responses of tobacco leaves to geographical location. Principal component analysis revealed obvious metabolic discrimination between growing districts relative to cultivars. A complex carbon and nitrogen metabolic network was modulated by environmental factors during growth. When the Xuchang and Dali Districts in China were compared, the results indicated that higher rates of photosynthesis, photorespiration and respiration were utilized in Xuchang District to generate the energy and carbon skeletons needed for the biosynthesis of nitrogen-containing metabolites. The increased abundance of defense-associated metabolites generated from the shikimate phenylpropanoid pathway in Xuchang relative to Dali was implicated in protection against stress. PMID- 26549190 TI - Comparative risk of oral ulcerations among antipsychotics users - population based retrospective cohort study. AB - PURPOSE: The study aimed to evaluate the comparative risk of oral ulcerations among antipsychotic medications. METHODS: We analyzed the National Health Insurance Research Database of Taiwan and included patients newly initiated with a single antipsychotic agent including haloperidol, sulpiride, olanzapine, quetiapine, risperidone, or amisulpride during 2002 to 2010. The outcome of interest was oral ulceration, defined by the presence diagnoses of stomatitis and mucositis, aphthous-like ulceration and oral burns, or dispensing of stomatological corticosteroids included triamcinolone, dexamethasone, hydrocortisone, and prednisolone. We conducted Cox proportional hazards regression to compare the risks of oral ulceration among antipsychotics. RESULTS: The rate of oral ulcerations was highest in the amisulpride group (217.7 per 1000 person-year), followed by quetiapine (193.9 per 1000 person-year), olanzapine (161.9 per 1000 person-year), sulpiride (147.1 per 1000 person-year), risperidone (115.6 per 1000 person-year), haloperidol (107.5 per 1000 person-year) and aripiprazole (49.8 per 1000 person-year). Compared with haloperidol users, the adjusted hazard ratio (AHR) was 1.40 (95% CI, 1.12-1.73) in olanzapine, 1.48 (95% CI, 1.30-1.69) in quetiapine, 1.27 (95% CI, 1.19-1.44) in sulpiride, 1.68 (95% CI, 0.97-2.59) in amisulpride, 1.02 (95% CI, 0.83-1.45) in risperidone, and 0.41 (95% CI, 0.24-0.72) in aripiprazole users by Cox regression model. CONCLUSION: Olanzapine, quetiapine, and sulpiride posed a higher risk, while aripiprazole posed a lower risk of oral ulcerations compared with haloperidol in subjects with newly initiated antipsychotic therapy. Risperidone and amisulpride tended to have higher risk of oral ulcerations, but this was not statistically significant. PMID- 26549192 TI - Why were doctors unable to accomplish their rural-aid mission in China? A qualitative study. AB - BACKGROUND: To alleviate the difficulties of rural residents in receiving timely healthcare, the Chinese government launched a medical rural-aid program that solicited urban medical professionals to go to rural hospitals for a 1-year tenure. However, many of urban doctors did not accomplish this task. In this study, we attempted to investigate the reasons behind the failure to fulfill this program and to explore a more feasible solution. METHODS: Eleven doctors and nurses participated in the focus group discussions. Twenty-five interviewees, including health administrative officials, doctors and managers from both urban tertiary hospitals and county-level hospitals, participated in semi-structured in depth telephone interviews. The interview data were summarized and analyzed using the grounded theory. RESULTS: The failure of this program was attributed to multiple causes, such as problems with the recipient hospitals, the support hospitals and the participating doctors, and overall defects in the program strategy itself. One major reason is the competition between the recipient hospitals and the support hospitals, which distorted the original purpose of this rural-aid program. CONCLUSION: The rural-aid program strategy should be adjusted. The recipient hospitals should be township-level health centers rather than county-level hospitals. In addition, the relevant policies should be amended and improved accordingly. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549191 TI - Rational design of a monomeric and photostable far-red fluorescent protein for fluorescence imaging in vivo. AB - Fluorescent proteins (FPs) are powerful tools for cell and molecular biology. Here based on structural analysis, a blue-shifted mutant of a recently engineered monomeric infrared fluorescent protein (mIFP) has been rationally designed. This variant, named iBlueberry, bears a single mutation that shifts both excitation and emission spectra by approximately 40 nm. Furthermore, iBlueberry is four times more photostable than mIFP, rendering it more advantageous for imaging protein dynamics. By tagging iBlueberry to centrin, it has been demonstrated that the fusion protein labels the centrosome in the developing zebrafish embryo. Together with GFP-labeled nucleus and tdTomato-labeled plasma membrane, time lapse imaging to visualize the dynamics of centrosomes in radial glia neural progenitors in the intact zebrafish brain has been demonstrated. It is further shown that iBlueberry can be used together with mIFP in two-color protein labeling in living cells and in two-color tumor labeling in mice. PMID- 26549193 TI - Different Omega-3 Formulations Yield to Diverse Clinical Response: A Case-Report. AB - Treatment guidelines recommend omega-3 with Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) content not above 85% in patients with high plasma levels of triglycerides. Since the different up to date formulation of omega-3 available in commerce must be similar to clinical efficacy and safety, herein, we report the case a 52-year-old woman who presented clinical inefficacy using Olevia((r)) omega-3 treatment. Clinical evaluation excluded the presence of intestinal or systemic diseases able to reduce the drug absorption. Switching the therapy from (Olevia((r))) to an equivalent omega-3 formulation (Esapent((r))), we documented a decrease in her plasma triglycerides levels. In order to evaluate a possible difference between these formulations we performed a single blind in vitro dissolution test using three pills for each formulation of omega-3 (Olevia((r)), Esapent(r) and another one chosen between the several formulations available in commerce: DOC Generic((r))) that revealed a significant difference (>20%) in the dissolution time of three different omega- 3 commercially available drug formulation. PMID- 26549194 TI - Higher Incentive Payments in Medicare Advantage's Pay-for-Performance Program Did Not Improve Quality But Did Increase Plan Offerings. AB - OBJECTIVE: To evaluate the effects of the size of financial bonuses on quality of care and the number of plan offerings in the Medicare Advantage Quality Bonus Payment Demonstration. DATA SOURCES: Publicly available data from CMS from 2009 to 2014 on Medicare Advantage plan quality ratings, the counties in the service area of each plan, and the benchmarks used to construct plan payments. STUDY DESIGN: The Medicare Advantage Quality Bonus Payment Demonstration began in 2012. Under the Demonstration, all Medicare Advantage plans were eligible to receive bonus payments based on plan-level quality scores (star ratings). In some counties, plans were eligible to receive bonus payments that were twice as large as in other counties. We used this variation in incentives to evaluate the effects of bonus size on star ratings and the number of plan offerings in the Demonstration using a differences-in-differences identification strategy. We used matching to create a comparison group of counties that did not receive double bonuses but had similar levels of the preintervention outcomes. PRINCIPAL FINDINGS: Results from the difference-in-differences analysis suggest that the receipt of double bonuses was not associated with an increase in star ratings. In the matched sample, the receipt of double bonuses was associated with a statistically insignificant increase of +0.034 (approximately 1 percent) in the average star rating (p > .10, 95 percent CI: -0.015, 0.083). In contrast, the receipt of double bonuses was associated with an increase in the number of plans offered. In the matched sample, the receipt of double bonuses was associated with an overall increase of +0.814 plans (approximately 5.8 percent) (p < .05, 95 percent CI: 0.078, 1.549). We estimate that the double bonuses increased payments by $3.43 billion over the first 3 years of the Demonstration. CONCLUSIONS: At great expense to Medicare, double bonuses in the Medicare Advantage Quality Bonus Payment Demonstration were not associated with improved quality but were associated with more plan offerings. PMID- 26549195 TI - Identification of lactic acid bacteria isolated from wine using real-time PCR. AB - Different lactic acid bacteria strains have been shown to cause wine spoilage, including the generation of substances undesirable for the health of wine consumers. The aim of this study was to investigate the occurrence of selected species of heterofermentative lactobacilli, specifically Lactobacillus brevis, Lactobacillus hilgardii, and Lactobacillus plantarum in six different Slovak red wines following the fermentation process. In order to identify the dominant Lactobacillus strain using quantitative (real time) polymerized chain reaction (qPCR) method, pure lyophilized bacterial cultures from the Czech Collection of Microorganisms were used. Six different red wine samples following malolactic fermentation were obtained from selected wineries. After collection, the samples were subjected to a classic plate dilution method for enumeration of lactobacilli cells. Real-time PCR was performed after DNA extraction from pure bacterial strains and wine samples. We used SYBR(r) Green master mix reagents for measuring the fluorescence in qPCR. The number of lactobacilli ranged from 3.60 to 5.02 log CFU mL(-1). Specific lactobacilli strains were confirmed by qPCR in all wine samples. The number of lactobacilli ranged from 10(3) to 10(6) CFU mL(-1). A melting curve with different melting temperatures (T(m)) of DNA amplicons was obtained after PCR for the comparison of T(m) of control and experimental portions, revealing that the most common species in wine samples was Lactobacillus plantarum with a T(m) of 84.64 degrees C. PMID- 26549196 TI - Aerobic Dimerization of Enediyne Compounds: Construction of Naphthalene Frameworks. AB - The first bimolecular oxygenative annulation of enediyne compounds leading to naphthalene frameworks has been developed by using Pd(OAc)2 as the catalyst in the presence of NaI under O2 (1 atm). This reaction provided efficient access to a class of symmetric core-annulated naphthalenes by the homoannulation of enediyne-imides. Intriguingly, the crossover annulation of enediyne-imides and other functionalized enediynes could also be achieved by the same catalytic system, resulting in the formation of several unsymmetrical naphthalene derivatives. Preliminary mechanistic investigation using (18) O isotopic labelling and radical scavengers indicated that radical oxygen incorporation cascades might be involved in this conversion. PMID- 26549197 TI - miR-150 Regulates Differentiation and Cytolytic Effector Function in CD8+ T cells. AB - MicroRNAs regulate most mammalian genes, and they control numerous aspects of immune system development and function. Their precise roles in the CD8+ T cell response, however, remain unclear. In this report, we show that in the absence of the microRNA miR-150, CD8+ T cells fail to undergo robust expansion and differentiation into short-lived terminal effector cells in response to primary infection with Listeria monocytogenes or Vaccinia virus. Notably, even after transitioning into the memory pool, miR-150(-/-) cells still mount a weaker recall response to secondary infection, and remain less differentiated than their wild-type counterparts. Transcriptome analysis shows miR-150 gene targets are globally upregulated in cells lacking miR-150, and amongst these targets, we found misregulation of genes associated with proliferation and effector cell function. These transcriptome data suggest that miR-150 deficient CD8+ T cells are less efficient in killing infected cells, which we validate experimentally. Together, these results reveal a cell-intrinsic role for miR-150 in the regulation of effector CD8+ T cell fate and function. PMID- 26549198 TI - Chromatographic elution process design space development for the purification of saponins in Panax notoginseng extract using a probability-based approach. AB - A Monte Carlo method was used to develop the design space of a chromatographic elution process for the purification of saponins in Panax notoginseng extract. During this process, saponin recovery ratios, saponin purity, and elution productivity are determined as process critical quality attributes, and ethanol concentration, elution rate, and elution volume are identified as critical process parameters. Quadratic equations between process critical quality attributes and critical process parameters were established using response surface methodology. Then probability-based design space was computed by calculating the prediction errors using Monte Carlo simulations. The influences of calculation parameters on computation results were investigated. The optimized calculation condition was as follows: calculation step length of 0.02, simulation times of 10 000, and a significance level value of 0.15 for adding or removing terms in a stepwise regression. Recommended normal operation region is located in ethanol concentration of 65.0-70.0%, elution rate of 1.7-2.0 bed volumes (BV)/h and elution volume of 3.0-3.6 BV. Verification experiments were carried out and the experimental values were in a good agreement with the predicted values. The application of present method is promising to develop a probability-based design space for other botanical drug manufacturing process. PMID- 26549200 TI - Natural Inhibitors of Lipase: Examining Lipolysis in a Single Droplet. AB - Inhibition of lipase activity is one of the approaches to reduced fat intake with nutritional prevention promoting healthier diet. The food industry is very interested in the use of natural extracts, hence reducing the side effects of commercial drugs inhibiting lipolysis. In this work we propose a novel methodology to rapidly assess lipolysis/inhibition in a single droplet by interfacial tension and dilatational elasticity. The evolution of the interfacial tension of lipase in simplified duodenal fluid in the absence and that in the presence of the pharmaceutical drug Xenical are the negative (5 +/- 1 mN/m) and positive (9 +/- 1 mN/m) controls of the inhibition of lipolysis, respectively. Then, we correlate the inhibition with the reduction of the interfacial activity of lipase and further identify the mode of action of the inhibition based on dilatational response (conformational changes induced in the molecule/blocking of adsorption sites). This work provides new insight into the lipase inhibition mechanism and a rapid methodology to identify the potential of new natural inhibitors. PMID- 26549199 TI - Hippocampal mitogen-activated protein kinase activation is associated with intermittent hypoxia in a rat model of obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/re oxygenation, may impair the cerebral system. Although mitogen-activated protein kinase (MAPK) signaling was observed to have a key role in hypoxia-induced brain injury, the intracellular events and their underlying mechanisms for intermittent hypoxia/re-oxygenation-associated damage to hippocamal MAPKs, including extracellular signal-regulated kinase (ERK)1/2, P38MAPK and c-Jun N-terminal kinase (JNK) remain to be elucidated and require further investigation. A total of five rats in each sub-group were exposed to intermittent hypoxia or continued hypoxia for 2, 4, 6 or 8 weeks. Histological, immunohistochemical and biological analyses were performed to assess nerve cell injury in the hippocampus. Surviving CA1 pyramidal cells were identified by hematoxylin and eosin staining. The levels of phosphorylated ERK1/2, P38MAPK and JNK were detected by western blotting. B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in neural cells were examined by immunohistochemistry. The malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities were measured by thiobarbituric acid and xanthine oxidation methods, respectively. Under continued hypoxia, the levels of phospho-ERK1/2 peaked at the fourth week and then declined, whereas phospho P38MAPK and JNK were detected only in the late stages. By contrast, under intermittent hypoxia, ERK1/2, P38MAPK and JNK were activated at all time-points assessed (2, 4, 6 and 8 weeks). The levels of phospho-ERK1/2, P38MAPK and JNK were all higher in the intermittent hypoxia groups than those in the corresponding continued hypoxia groups. Bcl-2 was mainly increased and reached the highest level at six weeks in the continued hypoxia group. Of note, Bcl-2 rapidly increased to the peak level at four weeks, followed by a decrease to the lowest level at the eighth week in the intermittent hypoxia group. Bax was generally increased at the late stages under continued hypoxia, but increased at all time-points under the intermittent hypoxia conditions. The two types of hypoxia induced an increase in the MDA content, but a decrease in SOD activity. Marked changes in these two parameters coupled with markedly reduced surviving cells in the hippocampus in a time-dependent manner were observed in the intermittent hypoxia group in comparison with the continued hypoxia group. OSAS induced intermittent hypoxia markedly activated the MAPK signaling pathways, which were triggered by oxidative stress, leading to abnormal expression of downstream Bcl-2 and Bax, and a severe loss of neural cells in the hippocampus. PMID- 26549201 TI - Gold over Branched Palladium Nanostructures for Photothermal Cancer Therapy. AB - Bimetallic nanostructures show exciting potential as materials for effective photothermal hyperthermia therapy. We report the seed-mediated synthesis of palladium-gold (Pd-Au) nanostructures containing multiple gold nanocrystals on highly branched palladium seeds. The nanostructures were synthesized via the addition of a gold precursor to a palladium seed solution in the presence of oleylamine, which acts as both a reducing and a stabilizing agent. The interaction and the electronic coupling between gold nanocrystals and between palladium and gold broadened and red-shifted the localized surface plasmon resonance absorption maximum of the gold nanocrystals into the near-infrared region, to give enhanced suitability for photothermal hyperthermia therapy. Pd-Au heterostructures irradiated with an 808 nm laser light caused destruction of HeLa cancer cells in vitro, as well as complete destruction of tumor xenographs in mouse models in vivo for effective photothermal hyperthermia. PMID- 26549203 TI - Rotational dynamics of organic cations in the CH3NH3PbI3 perovskite. AB - Methylammonium lead iodide (CH3NH3PbI3) based solar cells have shown impressive power conversion efficiencies of above 20%. However, the microscopic mechanism of the high photovoltaic performance is yet to be fully understood. Particularly, the dynamics of CH3NH3(+) cations and their impact on relevant processes such as charge recombination and exciton dissociation are still poorly understood. Here, using elastic and quasi-elastic neutron scattering techniques and group theoretical analysis, we studied rotational modes of the CH3NH3(+) cation in CH3NH3PbI3. Our results show that, in the cubic (T > 327 K) and tetragonal (165 K < T < 327 K) phases, the CH3NH3(+) ions exhibit four-fold rotational symmetry of the C-N axis (C4) along with three-fold rotation around the C-N axis (C3), while in the orthorhombic phase (T < 165 K) only C3 rotation is present. At around room temperature, the characteristic relaxation times for the C4 rotation are found to be tauC4 ~ 5 ps while for the C3 rotation tauC3 ~ 1 ps. The T-dependent rotational relaxation times were fitted with Arrhenius equations to obtain activation energies. Our data show a close correlation between the C4 rotational mode and the temperature dependent dielectric permittivity. Our findings on the rotational dynamics of CH3NH3(+) and the associated dipole have important implications for understanding the low exciton binding energy and a slow charge recombination rate in CH3NH3PbI3 which are directly relevant for the high solar cell performance. PMID- 26549204 TI - Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. AB - OBJECTIVE: To gain clinical experience on the effectiveness and safety of switching from infliximab-Remicade(INX) to infliximab-biosimilar-CT-P13(INB) in patients with established rheumatic disease. METHODS: Patients receiving INX treatment at a rheumatology clinic consented to switching from INX to INB. Patient reported outcomes (PROs), disease-activity, and inflammatory markers were recorded at every visit. Generalized estimating equation models and time dependent area under the curve (AUC) before/during INX and INB treatments were employed. RESULTS: Thirty-nine consecutive patients [mean (SD) age 53 (11), 17 F] with various rheumatic diseases were switched to INB after a mean (SD) of 4.1 (2.3) years on INX. Thirty-one patients were on concomitant methotrexate. At a median (range) of 11 (7.5-13) months following the first administration of INB, AUCs for disease activity and PROs were similar for INX and INB. They were better compared to those prior to INX. Eleven patients (28.2%) discontinued INB, due to INX antidrug antibodies detected prior to INB infusion (n = 3); latent tuberculosis (n = 1); new-onset neurofibromatosis (n = 1); subjective reasons with no objective deterioration of disease (n = 6). CONCLUSION: The clinical effectiveness of INB in both PROs and disease-activity measures was comparable to INX during the first year of switching, with no immediate safety signals. Subjective reasons (negative expectations) may play a role among discontinuations of biosimilars. Larger patient numbers and longer follow-up are necessary for confirming this clinical experience. PMID- 26549202 TI - Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression. AB - N-Methyl-d-aspartate receptors (NMDARs) are major targets of both acute and chronic alcohol, as well as regulators of plasticity in a number of brain regions. Aberrant plasticity may contribute to the treatment resistance and high relapse rates observed in alcoholics. Recent work suggests that chronic alcohol treatment preferentially modulates both the expression and subcellular localization of NMDARs containing the GluN2B subunit. Signaling through synaptic and extrasynaptic GluN2B-NMDARs has already been implicated in the pathophysiology of various other neurological disorders. NMDARs interact with a large number of proteins at the glutamate synapse, and a better understanding of how alcohol modulates this proteome is needed. We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol induced changes in GluN2B signaling complexes. Protein enrichment analyses revealed changes in the association of post-synaptic proteins, including scaffolding, glutamate receptor and PDZ-domain binding proteins with GluN2B. In particular, GluN2B interaction with metabotropic glutamate (mGlu)1/5 receptor dependent long-term depression (LTD)-associated proteins such as Arc and Homer 1 was increased, while GluA2 was decreased. Accordingly, we found a lack of mGlu1/5 -induced LTD while alpha1 -adrenergic receptor-induced LTD remained intact in hippocampal CA1 following CIE. These data suggest that CIE specifically disrupts mGlu1/5 -LTD, representing a possible connection between NMDAR and mGlu receptor signaling. These studies not only demonstrate a new way in which alcohol can modulate plasticity in the hippocampus but also emphasize the utility of this discovery-based proteomic approach to generate new hypotheses regarding alcohol related mechanisms. PMID- 26549205 TI - Endoperoxides Revealed as Origin of the Toxicity of Graphene Oxide. AB - Potential biomedicinal applications of graphene oxide (GO), for example, as a carrier of biomolecules or a reagent for photothermal therapy and biosensing, are limited by its cytotoxicity and mutagenicity. It is believed that these properties are at least partially caused by GO-induced oxidative stress in cells. However, it is not known which chemical fragments of GO are responsible for this unfavorable effect. We generated four GOs containing variable redox-active groups on the surface, including Mn(2+), C-centered radicals, and endoperoxides (EPs). A comparison of the abilities of these materials to generate reactive oxygen species in human cervical cancer cells revealed that EPs play a crucial role in GO-induced oxidative stress. These data could be applied to the rational design of biocompatible nontoxic GOs for biomedical applications. PMID- 26549206 TI - Chromosome-Based Proteomic Study for Identifying Novel Protein Variants from Human Hippocampal Tissue Using Customized neXtProt and GENCODE Databases. AB - The goal of the Chromosome-Centric Human Proteome Project (C-HPP) is to fully provide proteomic information from each human chromosome, including novel proteoforms, such as novel protein-coding variants expressed from noncoding genomic regions, alternative splicing variants (ASVs), and single amino acid variants (SAAVs). In the 144 LC/MS/MS raw files from human hippocampal tissues of control, epilepsy, and Alzheimer's disease, we identified the novel proteoforms with a workflow including integrated proteomic pipeline using three different search engines, MASCOT, SEQUEST, and MS-GF+. With a <1% false discovery rate (FDR) at the protein level, the 11 detected peptides mapped to four translated long noncoding RNA variants against the customized databases of GENCODE lncRNA, which also mapped to coding-proteins at different chromosomal sites. We also identified four novel ASVs against the customized databases of GENCODE transcript. The target peptides from the variants were validated by tandem MS fragmentation pattern from their corresponding synthetic peptides. Additionally, a total of 128 SAAVs paired with their wild-type peptides were identified with FDR <1% at the peptide level using a customized database from neXtProt including nonsynonymous single nucleotide polymorphism (nsSNP) information. Among these results, several novel variants related in neuro-degenerative disease were identified using the workflow that could be applicable to C-HPP studies. All raw files used in this study were deposited in ProteomeXchange (PXD000395). PMID- 26549207 TI - Stage IB cervix cancer with nodal involvement treated with primary surgery or primary radiotherapy: Patterns of failure and outcomes in a contemporary population. AB - INTRODUCTION: The purpose of this study is to evaluate patterns of failure, overall survival (OS), disease-free survival (DFS), prognostic factors and late toxicities in node positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB cervix cancer treated with curative intent. METHODS: Patients with FIGO stage IB cervix cancer and positive nodes were identified from the Peter MacCallum Cancer Centre prospective gynaecology database. Patients were treated with primary surgery and adjuvant radiotherapy (S + RT) or primary radiotherapy (primary RT). Prognostic factors examined were tumour size, histology, grade, lymphovascular invasion or corpus uterine invasion, MRI tumour volume, number of nodes involved, highest site of nodal involvement, treatment modality, age and smoking. RESULTS: Of the 103 eligible patients, 43 patients had S + RT and 60 patients had primary RT. Tumours were significantly smaller in the S + RT group (mean 3.0 cm vs. 4.5 cm, P < 0.001). Five-year OS (95% confidence interval) and DFS (95% confidence interval) for the whole cohort was 67.6% (56.5 76.4%) and 66.1% (55.7-74.6%), respectively. Tumour diameter and number of positive nodes were significant prognostic factors for OS and DFS and smoking was related to DFS. Treatment modality was not a significant prognostic factor in OS and DFS. Of 33 patients that relapsed, 32 patients relapsed outside the pelvis. One patient failed in the pelvis only. CONCLUSIONS: Early stage cervix cancer with nodal involvement is associated with excellent pelvic disease control following curative intent treatment. Almost all relapses occurred beyond the pelvis and therefore more aggressive local treatment is unlikely to improve survival in these patients. PMID- 26549208 TI - Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems. AB - Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-pi interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates. PMID- 26549209 TI - Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism. AB - A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m2). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH <1.0 pg/mL, and cortisol 21.6 MUg/dL. Liquid chromatography-tandem mass spectrometry analysis showed that aldosterone (104 times the control) as well as its precursors were significantly elevated in the patient's plasma. A left adrenal (4-cm-diameter) tumor with 131I Adosterol uptake was found and removed. Four days later, plasma aldosterone and renin activity had dropped to 7.73 ng/dL and 1.6 ng/mL/hr, respectively. However, they rose to 24.0 ng/dL and 10.9 ng/mL/hr, respectively, by Day 102. Nevertheless, magnetic resonance angiography found no evidence of a renovascular lesion. The tumor was a benign adrenocortical adenoma composed predominantly of clear cells positive for 17alpha-hydroxylase, [hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerases], and aldosterone synthase. A quantitative real-time polymerase chain reaction analysis of the tumor cells revealed that expression of the gene encoding aldosterone synthase was 85 times the control level. In addition, the tumor cells harbored G151R mutation of the inward rectifying potassium channel subfamily j, member 5 gene. The striking overexpression of aldosterone synthase by the tumor cells was considered the primary mechanism for the extravagant overproduction of aldosterone in this case. This overexpression may have resulted from integration of signals from AII and forced membrane depolarization due to the potassium channel mutation. PMID- 26549210 TI - SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies. AB - Diabetes mellitus complicated with insulin antibodies is rare in clinical practice but usually difficult to control. A high amount of insulin antibodies, especially with low affinity and high binding capacity, leads to unstable glycemic control characterized by hyperglycemia unresponsive to large volume of insulin and unanticipated hypoglycemia. There are several treatment options, such as changing insulin preparation, immunosupression with glucocorticoids, and plasmapheresis, most of which are of limited efficacy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drug which decrease renal glucose reabsorption and lowers plasma glucose level independent of insulin action. We report here a case with diabetes complicated with insulin antibodies who was effectively controlled by an SGLT2 inhibitor. A 47-year-old man with type 2 diabetes treated with insulin had very poor glycemic control characterized by postprandial hyperglycemia unresponsive to insulin therapy and repetitive hypoglycemia due to insulin antibodies. Treatment with ipragliflozin, an SGLT2 inhibitor, improved HbA1c from 8.4% to 6.0% and glycated albumin from 29.4% to 17.9%. Continuous glucose monitoring revealed improvement of glycemic profile (average glucose level from 212 mg/dL to 99 mg/dL and glycemic standard deviation from 92 mg/dL to 14 mg/dL) with disappearance of hypoglycemic events. This treatment further ameliorated the characteristics of insulin antibodies and resulted in reduced insulin requirement. SGLT2 inhibitors may offer an effective treatment option for managing the poor glycemic control in diabetes complicated with insulin antibodies. PMID- 26549212 TI - Electric field generation of Skyrmion-like structures in a nematic liquid crystal. AB - Skyrmions are particle-like topological objects that are increasingly drawing attention in condensed matter physics, where they are connected to inversion symmetry breaking and chirality. Here we report the generation of stable Skyrmion like structures in a thin nematic liquid crystal film on chemically patterned patchy surfaces. Using the interplay of material elasticity and surface boundary conditions, we use a strong electric field to quench the nematic liquid crystal from a fully aligned phase to vortex-like nematic liquid crystal structures, centered on patterned patches, which carry two different sorts of topological defects. Numerical calculations reveal that these are Skyrmion-like structures, seeded from the surface boojum topological defects and swirling towards the second confining surface. These observations, supported by numerical methods, demonstrate the possibility to generate, manipulate and study Skyrmion-like objects in nematic liquid crystals on patterned surfaces. PMID- 26549211 TI - Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease. AB - The age-dependent deposition of amyloid-beta peptides, derived from amyloid precursor protein (APP), is a neuropathological hallmark of Alzheimer's disease (AD). Despite age being the greatest risk factor for AD, the molecular mechanisms linking ageing to APP processing are unknown. Here we show that asparagine endopeptidase (AEP), a pH-controlled cysteine proteinase, is activated during ageing and mediates APP proteolytic processing. AEP cleaves APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP is activated in normal mice in an age-dependent manner, and is strongly activated in 5XFAD transgenic mouse model and human AD brains. Deletion of AEP from 5XFAD or APP/PS1 mice decreases senile plaque formation, ameliorates synapse loss, elevates long-term potentiation and protects memory. Blockade of APP cleavage by AEP in mice alleviates pathological and behavioural deficits. Thus, AEP acts as a delta-secretase, contributing to the age-dependent pathogenic mechanisms in AD. PMID- 26549213 TI - Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK. AB - Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) 1beta and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades. PMID- 26549214 TI - Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area in rats. AB - Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Two weeks later, rats were treated with 30 mg/kg fluoxetine (intragastric injection, i.g.) for 6 weeks. Cognitive function was evaluated by Morris water maze (MWM) and novel objects recognition (NOR) test. Long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Western blotting was used to quantify the protein levels. Our results showed that fluoxetine treatment significantly improved the cognitive impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, 2VO caused an up-regulation of hyperpolarization activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 surface expressions, which may be a possible mechanism that fluoxetine treatment ameliorates cognitive impairments in rats with CCH. PMID- 26549215 TI - Speckle-Tracking Echocardiography to Detect Cardiac Toxicity in Children Who Received Anthracyclines During Pregnancy. AB - Cardiac toxicities remain a possible risk to fetuses that received anthracyclines during pregnancy. The introduction of new echocardiographic techniques will improve the detection of early cardiac damage. Thus, we began a observational study using speckle-tracking echocardiography (STE) in children who had received anthracyclines during pregnancy, including the first trimester. From 2009 to 2013, we performed STE on patients > 5 years old, whose mothers had received anthracyclines during pregnancy. Siblings or cousins of equivalent age and gender were used as the control group. A total of 90 children fulfilled the entry criteria. Our results with STE were normal in all echocardiography parameters and did not show any differences when compared with the findings from the control group. We consider that the use of anthracyclines during pregnancy does not produce cardiac damage in newborns and can be safely administered, because no cardiac toxicity was evident in these children and it is of benefit to the mother. PMID- 26549217 TI - Are Technology Interruptions Impacting Your Bottom Line? An Innovative Proposal for Change. AB - BACKGROUND: Nursing interruptions are a costly and dangerous variable in acute care hospitals. Malfunctioning technology equipment interrupts nursing care and prevents full utilization of computer safety systems to prevent patient care errors. AIMS: This paper identifies an innovative approach to nursing interruptions related to computer and computer cart malfunctions. The impact on human resources is defined and outcome measures were proposed. A multifaceted proposal, based on a literature review, aimed at reducing nursing interruptions is presented. This proposal is expected to increase patient safety, as well as patient and nurse satisfaction. SETTING: Acute care hospitals utilizing electronic medical records and bar-coded medication administration technology. PARTICIPANTS: Nurses, information technology staff, nursing informatics staff, and all leadership teams affected by technology problems and their proposed solutions. METHODS: Literature from multiple fields was reviewed to evaluate research related to computer/computer cart failures, and the approaches used to resolve these issues. RESULTS: Outcome measured strategic goals related to patient safety, and nurse and patient satisfaction. Specific help desk metrics will demonstrate the effect of interventions. CONCLUSIONS: This paper addresses a gap in the literature and proposes practical and innovative solutions. A comprehensive computer and computer cart repair program is essential for patient safety, financial stewardship, and utilization of resources. PMID- 26549216 TI - The genetic regulatory network centered on Pto-Wuschela and its targets involved in wood formation revealed by association studies. AB - Transcription factors (TFs) regulate gene expression and can strongly affect phenotypes. However, few studies have examined TF variants and TF interactions with their targets in plants. Here, we used genetic association in 435 unrelated individuals of Populus tomentosa to explore the variants in Pto-Wuschela and its targets to decipher the genetic regulatory network of Pto-Wuschela. Our bioinformatics and co-expression analysis identified 53 genes with the motif TCACGTGA as putative targets of Pto-Wuschela. Single-marker association analysis showed that Pto-Wuschela was associated with wood properties, which is in agreement with the observation that it has higher expression in stem vascular tissues in Populus. Also, SNPs in the 53 targets were associated with growth or wood properties under additive or dominance effects, suggesting these genes and Pto-Wuschela may act in the same genetic pathways that affect variation in these quantitative traits. Epistasis analysis indicated that 75.5% of these genes directly or indirectly interacted Pto-Wuschela, revealing the coordinated genetic regulatory network formed by Pto-Wuschela and its targets. Thus, our study provides an alternative method for dissection of the interactions between a TF and its targets, which will strength our understanding of the regulatory roles of TFs in complex traits in plants. PMID- 26549218 TI - Correlates of nutrition label use among college students and young adults: a review. AB - OBJECTIVE: Nutrition labels are an essential source for consumers to obtain nutrition-related information on food products and serve as a population-level intervention with unparalleled reach. The present study systematically reviewed existing evidence on the correlates of nutrition label use among college students and young adults. DESIGN: Keyword and reference searches were conducted in PubMed, EBSCO, PsycInfo, Cochrane Library and Web of Science. Inclusion criteria included: study design (randomized controlled trial, cohort study, pre-post study or cross-sectional study); population (college students and young adults 18-30 years old); main outcome (nutrition label use); article type (peer-reviewed publication); and language (English). SETTING: College/university. SUBJECTS: College students and young adults. RESULTS: Sixteen studies based on data from college surveys in four countries (USA, UK, Canada, South Korea) were identified from keyword and reference search. Reported prevalence of nutrition label use varied substantially across studies; a weighted average calculation showed 36.5 % of college students and young adults reported using labels always or often. Females were more likely to use nutrition labels than males. Nutrition label use was found to be associated with attitudes towards healthy diet, beliefs on the importance of nutrition labels in guiding food selection, self-efficacy, and nutrition knowledge and education. CONCLUSIONS: The impact of nutrition labelling on food purchase and intake could differ by population subgroups. Nutrition awareness campaigns and education programmes may be important mechanisms for promoting nutrition label use among college students and young adults. Future research is warranted to assess the role of label use on improved dietary decisions. PMID- 26549219 TI - DNA Methylation of MMP9 Is Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions. AB - INTRODUCTION: Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation. METHODS: Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction. RESULTS: All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues. CONCLUSIONS: The present study suggests that the unmethylated status of the MMP9 gene in periapical lesions may explain the observed up-regulation of messenger RNA transcription in these lesions. PMID- 26549220 TI - The Effect of Foraminal Enlargement of Necrotic Teeth with the Reciproc System on Postoperative Pain: A Prospective and Randomized Clinical Trial. AB - INTRODUCTION: The aim of this prospective study was to evaluate the postoperative pain that followed root canal treatments performed with a single-file reciprocating system on asymptomatic uniradicular necrotic teeth with and without foraminal enlargements (FEs). METHODS: Forty-six volunteers were randomly divided into 2 groups according to the established working lengths. The FE group had a working length of 0.0 mm from the apex, and the control group had a working length of 1.0 mm short of the apex. The treatments of both groups were performed with a Reciproc R40 (VDW, Munich, Germany) instrument. Both groups underwent the same treatment protocol with the exception of the established working length. The volunteers were instructed to record their pain (none, mild, moderate, or severe) on a visual analog scale at 24 hours, 72 hours, and 1 week after the procedures. The Kruskal-Wallis test was used to identify significant differences. RESULTS: Overall, 82.22% of the patients indicated no pain or mild pain. A greater proportion of the patients in the FE group reported mild pain compared with patients in the control group in the first 24 hours (P < .05). At 72 hours and 1 week, there were no statistically significant differences between the groups (P > .05). CONCLUSIONS: FEs during endodontic treatments of asymptomatic necrotic, uniradicular teeth that were performed in single visits using the Reciproc R40 reciprocating file resulted in a low incidence of pain. After 24 hours, the FEs resulted in more patients reporting mild pain compared with the control group, but no differences were observed at 72 hours or 1 week. PMID- 26549221 TI - Clinical Antibacterial Effectiveness of Root Canal Preparation with Reciprocating Single-instrument or Continuously Rotating Multi-instrument Systems. AB - INTRODUCTION: This in vivo study compared the antibacterial effectiveness of a reciprocating single-instrument system (Reciproc; VDW, Munich, Germany) and a rotary multi-instrument system (BioRaCe; FKG Dentaire, La Chaux-de-Fonds, Switzerland) during the preparation of infected root canals of teeth with primary apical periodontitis. METHODS: Root canals from single-rooted teeth with necrotic pulps and apical periodontitis were instrumented using either Reciproc (n = 29) or BioRaCe (n = 30) instruments under irrigation with 2.5% sodium hypochlorite. DNA was extracted from samples taken before and after preparation and subjected to quantitative analysis of total bacteria and streptococci by using the quantitative real-time polymerase chain reaction. RESULTS: All initial samples were positive for the presence of bacteria, with median numbers of 7.1 * 10(5) and 1.31 * 10(5) bacterial cells for the Reciproc and BioRaCe groups, respectively. After preparation with Reciproc and BioRaCe, 16 (55%) and 15 (50%) root canals still had detectable bacteria with median counts of 7.05 * 10(2) and 6.03 * 10(1), respectively. Both systems were highly effective in reducing the total bacterial counts (P < .001), and there were no significant differences between them (P > .05). Streptococci were highly frequent, and both systems succeeded in significantly reducing their levels (P < .001). CONCLUSIONS: Both reciprocating single-instrument and rotary multi-instrument systems were highly effective in reducing the counts of total bacteria and streptococci in root canals of teeth with apical periodontitis. Regardless of the system used, approximately one half of the teeth still had detectable bacteria. PMID- 26549222 TI - Evaluation and Comparison of Occurrence of Tooth Discoloration after the Application of Various Calcium Silicate-based Cements: An Ex Vivo Study. AB - INTRODUCTION: Biodentine (Septodont, Saint Maur des Fosses, France), OrthoMTA (BioMTA, Seoul, Korea), and EndoSequence Root Repair Material (ERRM; Brasseler, Savannah, GA) have been developed to overcome the shortcomings of mineral trioxide aggregate (MTA). The purpose of this study was to compare tooth discoloration after the application of ProRoot MTA (Dentsply Tulsa Dental Products, Tulsa, OK) and 3 recently introduced calcium silicate-based cements in the presence and absence of blood. METHODS: In total, 104 human anterior teeth were prepared; 96 were randomly divided into 2 groups (blood and saline contamination). Each group was subdivided into 4 experimental subgroups (n = 12) of ProRoot MTA, Biodentine, OrthoMTA, and ERRM that were used to fill the pulp chambers. The remaining 8 teeth served as the saline and blood groups. Color analysis of tooth crowns was performed using a spectroradiometer before the application of materials and at 24 hours, 1 month, and 6 months after application. Repeated measures analysis of variance was used to evaluate the effects of blood, material, and time on color change (DeltaE*). RESULTS: Tooth color change in all experimental groups increased over time (P < .05). Blood contamination significantly increased DeltaE* (P < .05), but no significant difference occurred between the 4 groups in this respect in the presence of blood. However, in the absence of blood, the DeltaE* of Biodentine and ERRM was significantly less than that of OrthoMTA (P < .05). CONCLUSIONS: There was no significant difference between tooth discolorations with materials in the presence of blood. However, in the absence of blood, Biodentine and ERRM exhibited less tooth discoloration than OrthoMTA. PMID- 26549223 TI - High-resolution FTIR imaging of colon tissues for elucidation of individual cellular and histopathological features. AB - Novel technologies that could complement current histopathology based cancer diagnostic methods are under examination. In this endeavour mid-infrared spectroscopic imaging is a promising candidate that can provide valuable bio molecular information from unstained cells and tissues in a rapid and a non destructive manner. With this imaging technique, the biochemical information obtained from smaller areas of the tissues can be of clinical significance and hence the measured pixel size. Until recently it was difficult to obtain spectral data from pixels below around 5 microns square. High NA objectives have been utilised to reduce the ideal diffraction limit, enabling for the first time elucidation of subcellular features. In this context, the ability of high resolution imaging, obtained using novel high-magnification optics retro-fitted onto a bench top FTIR imaging system, to characterise histopathological features in colonic tissues has been tested. Formalin fixed paraffin embedded colon tissues from three different pathologies were imaged directly using the conventional and the high-magnification imaging set-ups. To circumvent chemical de-paraffinization protocols, an extended multiplicative signal correction (EMSC) based electronic de-paraffinization was carried out on all the infrared images. Multivariate analysis of the high-magnification infrared imaging data showed a detailed information of the histological features of the colon tissue in comparison to conventional imaging. Furthermore, high-magnification imaging has enabled a label-free characterization of the mucin rich goblet cell features in an unprecedented manner. The current study demonstrates the applicability of high magnification FTIR imaging to characterise complex tissues on a smaller scale that could be of clinical significance. PMID- 26549224 TI - Effects of an entomopathogen nematode on the immune response of the insect pest red palm weevil: Focus on the host antimicrobial response. AB - Relationships between parasites and hosts can be drastic, depending on the balance between parasite strategies and the efficiency of the host immune response. In the case of entomopathogenic nematodes and their insect hosts, we must also consider the role of bacterial symbionts, as the interaction among them is tripartite and each component plays a critical role in death or survival. We analyzed the effects induced by the nematode-bacteria complex Steinernema carpocapsae, against red palm weevil (RPW) larvae, Rhynchophorus ferrugineus. We examined the antimicrobial response of the insect when in the presence of nematocomplexes or of its symbionts, Xenorhabdus nematophila. In detail, we investigated the potential interference of live and dead S. carpocapsae, their isolated cuticles, live or dead bacterial symbionts and their lipopolysaccharides, on the synthesis and activity of host antimicrobial peptides. Our data indicate that both live nematodes and live bacterial symbionts are able to depress the host antimicrobial response. When nematodes or symbionts were killed, they lacked inhibitory properties, as detected by the presence of antimicrobial peptides (AMPs) in the host hemolymph and by assays of antimicrobial activity. Moreover, we isolated S. carpocapsae cuticles; when cuticles were injected into hosts they revealed evasive properties because they were not immunogenic and were not recognized by the host immune system. We observed that weevil AMPs did not damage X. nematophila, and the lipopolysaccharides purified from symbionts seemed to be non-immunogenic. We believe that our data provide more information on the biology of entomopathogenic nematodes, in particular concerning their role and the activity mediated by symbionts in the relationship with insect hosts. PMID- 26549225 TI - Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells through down regulating the transcriptional co-activator TAZ. AB - Microgravity induces observed bone loss in space flight or simulated experiments, while the mechanism underlying it is still obscure. Here, we utilized a clinostat to model simulated microgravity (SMG) and found that SMG obviously inhibited osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). We detected that SMG dramatically inhibited the expression of the transcriptional coactivator with PDZ-binding motif (TAZ), which acts as a vital regulator of osteogenesis. Interestingly, we found that lysophosphatidic acid (LPA) could activate TAZ and retain osteogenic differentiation of BMSCs under SMG. Our data further demonstrated that depletion of TAZ by siRNA blocked the LPA-induced increase in osteogenic differentiation of BMSCs under SMG. Moreover, Y27632 (the Rock inhibitor) abrogated the activation of TAZ and the increased osteogenic differentiation induced by LPA. Taken together, we propose that microgravity inhibits osteogenic differentiation of BMSCs due to decreased TAZ expression and that LPA can efficiently reverse the reduced osteogenic differentiation via the Rock-TAZ pathway. PMID- 26549226 TI - Cryo-EM of the pathogenic VCP variant R155P reveals long-range conformational changes in the D2 ATPase ring. AB - Single amino acid mutations in valosin containing protein (VCP/p97), a highly conserved member of the ATPases associated with diverse cellular activities (AAA) family of ATPases has been linked to a severe degenerative disease affecting brain, muscle and bone tissue. Previous studies have demonstrated the role of VCP mutations in altering the ATPase activity of the D2 ring; however the structural consequences of these mutations remain unclear. In this study, we report the three-dimensional (3D) map of the pathogenic VCP variant, R155P, as revealed by single-particle Cryo-Electron Microscopy (EM) analysis at 14 A resolution. We show that the N-terminal R155P mutation induces a large structural reorganisation of the D2 ATPase ring. Results from docking studies using crystal structure data of available wild-type VCP in the EM density maps indicate that the major difference is localized at the interface between two protomers within the D2 ring. Consistent with a conformational change, the VCP R155P variant shifted the isoelectric point of the protein and reduced its interaction with its well characterized cofactor, nuclear protein localization-4 (Npl4). Together, our results demonstrate that a single amino acid substitution in the N-terminal domain can relay long-range conformational changes to the distal D2 ATPase ring. Our results provide the first structural clues of how VCP mutations may influence the activity and function of the D2 ATPase ring. PMID- 26549227 TI - MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. AB - MicroRNAs acting as oncogenes or tumor suppressor genes play crucial roles in human cancers. Sphingosine kinase 1 (SPHK1) and its metabolite sphingosine 1 phosphate (S1P) contribute to tumor angiogenesis. We have reported that the down regulation of miR-506 targeting YAP mRNA results in the hepatocarcinogenesis. In the present study, we report a novel function of miR-506, which suppresses tumor angiogenesis through targeting SPHK1 mRNA in liver cancer. Bioinformatics analysis showed that miR-506 might target 3'-untranslated region (3'UTR) of SPHK1 mRNA. Then, we validated that by luciferase reporter gene assays. MiR-506 was able to reduce the expression of SPHK1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis in hepatoma HepG2 cells. Functionally, human umbilical vein endothelial cell (HUVEC) tube formation assays demonstrated that the forced miR-506 expression remarkably inhibited the production of S1P in the supernatant of hepatoma cells. The supernatant resulted in the inhibition of tumor angiogenesis. Interestingly, the supernatant with overexpression of SPHK1 could rescue the inhibition of angiogenesis of liver cancer mediated by miR-506. Anti-miR-506 increased the production of S1P in the supernatant of hepatoma cells, but the supernatant with silencing of SPHK1 abolished anti-miR-506-induced acceleration of tumor angiogenesis. Clinically, we observed that the levels of miR-506 were negatively related to those of SPHK1 mRNA in liver cancer tissues. Thus, we conclude that miR-506 depresses the angiogenesis of liver cancer through targeting 3'UTR of SPHK1 mRNA. Our finding provides new insights into the mechanism of tumor angiogenesis. PMID- 26549228 TI - Repression of HNF1alpha-mediated transcription by amino-terminal enhancer of split (AES). AB - HNF1alpha (Hepatocyte Nuclear Factor 1alpha) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1alpha are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1alpha exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1alpha-specific physical binding partner and functional repressor of HNF1alpha-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1alpha mutation-driven diabetes. PMID- 26549229 TI - Crystal structure of cyclic nucleotide-binding-like protein from Brucella abortus. AB - The cyclic nucleotide-binding (CNB)-like protein (CNB-L) from Brucella abortus shares sequence homology with CNB domain-containing proteins. We determined the crystal structure of CNB-L at 2.0 A resolution in the absence of its C-terminal helix and nucleotide. The 3D structure of CNB-L is in a two-fold symmetric form. Each protomer shows high structure similarity to that of cGMP-binding domain containing proteins, and likely mimics their nucleotide-free conformation. A key residue, Glu17, mediates the dimerization and prevents binding of cNMP to the canonical ligand-pocket. The structurally observed dimer of CNB-L is stable in solution, and thus is likely to be biologically relevant. PMID- 26549230 TI - Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis. AB - Cep169 is a centrosomal protein conserved among vertebrates. In our previous reports, we showed that mammalian Cep169 interacts and collaborates with CDK5RAP2 to regulate microtubule (MT) dynamics and stabilization. Although Cep169 is required for MT regulation, its precise cellular function remains largely elusive. Here we show that Cep169 associates with centrosomes during interphase, but dissociates from these structures from the onset of mitosis, although CDK5RAP2 (Cep215) is continuously located at the centrosomes throughout cell cycle. Interestingly, treatment with purvalanol A, a Cdk1 inhibitor, nearly completely blocked the dissociation of Cep169 from centrosomes during mitosis. In addition, mass spectrometry analyses identified 7 phosphorylated residues of Cep169 corresponding to consensus phosphorylation sequence for Cdk1. These data suggest that the dissociation of Cep169 from centrosomes is controlled by Cdk1/Cyclin B during mitosis, and that Cep169 might regulate MT dynamics of mitotic spindle. PMID- 26549231 TI - 24-Methylenecycloartanyl ferulate, a major compound of gamma-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator activated receptor-gamma 2 in human breast cancer cells. AB - Parvin-beta is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a gamma-oryzanol compound. We observed upregulation of parvin-beta (GenBank Accession No. AF237769) and peroxisome proliferator-activated receptor (PPAR)-gamma2 (GenBank Accession No. NM_015869). Among gamma-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-beta (650 and 500 bp) and PPAR-gamma2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-beta in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-beta expression and induction of PPAR-gamma2. This hypothesis was investigated by using a promoter reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-gamma2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin beta promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 MUM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: 3OCB) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-beta expression, which may inhibit ILK downstream signaling. PMID- 26549232 TI - Merlin negative regulation by miR-146a promotes cell transformation. AB - Inactivation of the tumor suppressor Merlin, by deleterious mutations or by protein degradation via sustained growth factor receptor signaling-mediated mechanisms, results in cell transformation and tumor development. In addition to these mechanisms, here we show that, miRNA-dependent negative regulation of Merlin protein levels also promotes cell transformation. We provide experimental evidences showing that miR-146a negatively regulates Merlin protein levels through its interaction with an evolutionary conserved sequence in the 3' untranslated region of the NF2 mRNA. Merlin downregulation by miR-146a in A549 lung epithelial cells resulted in enhanced cell proliferation, migration and tissue invasion. Accordingly, stable miR-146a-transfectant cells formed tumors with metastatic capacity in vivo. Together our results uncover miRNAs as yet another negative mechanism controlling Merlin tumor suppressor functions. PMID- 26549233 TI - The calcium sensor CBL7 modulates plant responses to low nitrate in Arabidopsis. AB - Calcium (Ca(2+)) serves as a critical messenger in a number of adaptation and developmental processes. In plants, CBL family represents a unique group of calcium sensors that decodes calcium signals. Several CBL members have been functionally characterized in the model plant Arabidopsis thaliana, but the role of CBL7 remains unknown. Here, we report that CBL7 is involved in the regulation of low-nitrate response in Arabidopsis. Expression of CBL7 was predominant in the root of young seedlings and substantially induced by nitrate starvation. Cbl7 mutant was more inhibited in root growth upon nitrate starvation compared to the wild-type. Interestingly, the growth arrest of cbl7 under low-nitrate conditions relied on acidic pH. Further analyses revealed that expression of two high affinity nitrate transporter genes, NRT2.4 and NRT2.5, was down-regulated in cbl7 under nitrogen-starvation condition. Accordingly, the cbl7 mutant plants retained lower nitrate content than wild-type plants under low-nitrate condition. Taken together, our results uncover a novel role of CBL7 in the response to nitrate deficiency in Arabidopsis. PMID- 26549234 TI - MiR-221 activates the NF-kappaB pathway by targeting A20. AB - MicroRNAs play an important role in regulating the inflammatory response, and are critically involved in the development of inflammatory disorders, including those affecting the lungs. While the microRNA miR-221 is involved in embryonic lung branching morphogenesis and epithelial cell development, its importance in lung inflammation has not been previously explored. In our current study, expression of miR-221 was selectively decreased by exposure to lipopolysaccharides (LPS) both in vitro and in vivo. Enforced expression of miR-221 significantly increased the production of proinflammatory cytokines TNF-alpha and IL-6, and enhanced the activation of NF-kappaB and MAPKs upon LPS stimulation. Accordingly, intratracheal stimulation of miR-221 was shown to aggravate endotoxin-induced acute lung injuries and inflammation in mice. Mechanistic studies showed that miR 221 directly targets A20, a master regulator of NF-kappaB and MAPK signaling, and thus represses inflammatory signaling. Restoration of A20 in macrophages abolished the stimulatory effect of miR-221 on production of proinflammatory cytokines. Together, these results indicate the presence of a novel miRNA mediated feed-back mechanism that controls inflammation, and suggest involvement of aberrant miR-221 expression in the development of inflammatory lung disorders. PMID- 26549235 TI - Mycoplasma gallisepticum (HS strain) surface lipoprotein pMGA interacts with host apolipoprotein A-I during infection in chicken. AB - The adhesin protein from Mycoplasma gallisepticum (HS strain), namely pMGA1.2, is required for M. gallisepticum (MG) infection in chicken. However, the host factor(s) that interact with pMGA1.2 is not known. In this study, we prepared the membrane fraction of trachea epithelial cells from chicken embryos. Using an improved virus overlay protein blot assay (VOPBA) and glutathione S-transferase (GST) pull-down assay, we found that pMGA1.2 specifically bound to a ~30 kDa host protein. This host protein was further identified by mass spectrometry as chicken apolipoprotein A-I (ApoA-I). We expressed and purified the recombinant ApoA-I protein in Escherichia coli and confirmed that it bound to the purified pMGA1.2 protein in vitro. Transiently expressed pMGA1.2 and ApoA-I were colocalized in HeLa cells. Finally, we designed small interfering RNA (siRNA) molecules to knock down the expression of either ApoA-I or pMGA1.2, which inhibited the MG-induced cell cycle disruption in cells of chicken embryo fibroblast cell line (DF-1). Similarly, knockdown of ApoA-I inhibited the cilia loss and damage in chicken trachea cells in MG infection. In summary, ApoA-I may be an essential host factor in MG infection through interacting with pMGA1.2. PMID- 26549237 TI - Bacteria as source of diglycosidase activity: Actinoplanes missouriensis produces 6-O-alpha-L-rhamnosyl-beta-D-glucosidase active on flavonoids. AB - Bacteria represent an underexplored source of diglycosidases. Twenty-five bacterial strains from the genera Actinoplanes, Bacillus, Corynebacterium, Microbacterium, and Streptomyces were selected for their ability to grow in diglycosylated flavonoids-based media. The strains Actinoplanes missouriensis and Actinoplanes liguriae exhibited hesperidin deglycosylation activity (6-O-alpha-L rhamnosyl-beta-D-glucosidase activity, EC 3.2.1.168), which was 3 to 4 orders of magnitude higher than the corresponding monoglycosidase activities. The diglycosidase production was confirmed in A. missouriensis by zymographic assays and NMR analysis of the released disaccharide, rutinose. The gene encoding the 6 O-alpha-L-rhamnosyl-beta-D-glucosidase was identified in the genome sequence of A. missouriensis 431(T) (GenBank accession number BAL86042.1) and functionally expressed in Escherichia coli. The recombinant protein hydrolyzed hesperidin and hesperidin methylchalcone, but not rutin, which indicates its specificity for 7-O rutinosylated flavonoids. The protein was classified into the glycoside hydrolase family 55 (GH55) in contrast to the known eukaryotic diglycosidases, which belong to GH1 and GH5. These findings demonstrate that organisms other than plants and filamentous fungi can contribute to an expansion of the diglycosidase toolbox. PMID- 26549238 TI - Long-term effects of heavy metals and antibiotics on granule-based anammox process: granule property and performance evolution. AB - The feasibility of the anaerobic ammonium oxidation (anammox) process to treat synthetic swine wastewater containing antibiotics and heavy metals was studied in this work. Nitrogen removal performance and granule characteristics were tracked by continuous-flow monitoring to evaluate the long-term joint effects of Cu and Zn and of Cu and oxytetracycline (OTC). Cu and Zn with a joint loading rate (JLR) of 0.04 kg m(-3) day(-1) did not affect the performance, while a JLR of 0.12 kg m(-3) day(-1) caused a rapid collapse in performance. Cu and OTC addition with a JLR of 0.04 kg m(-3) day(-1) for approximately 2 weeks induced significant nitrite accumulation. Granule characteristic analysis elucidated the disparate inhibition mechanisms of heavy metals and antibiotics: the internalization of heavy metals caused metabolic disorders, whereas OTC functioned as a growth retarder. However, anammox reactors could adapt to a JLR of 0.04 kg m(-3) day(-1) via self-regulation during the acclimatization to subinhibitory concentrations, which had a stable nitrogen removal rate (>8.5 kg m(-3) day(-1)) and removal rate efficiency (>75 %) for reactors with Cu-OTC addition. Therefore, this study supports the great potential of using anammox granules to treat swine wastewater. PMID- 26549236 TI - Iterative polyketide biosynthesis by modular polyketide synthases in bacteria. AB - Modular polyketide synthases (type I PKSs) in bacteria are responsible for synthesizing a significant percentage of bioactive natural products. This group of synthases has a characteristic modular organization, and each module within a PKS carries out one cycle of polyketide chain elongation; thus each module is non iterative in function. It was possible to predict the basic structure of a polyketide product from the module organization of the PKSs, since there generally existed a co-linearity between the number of modules and the number of chain elongations. However, more and more bacterial modular PKSs fail to conform to the canonical rules, and a particularly noteworthy group of non-canonical PKSs is the bacterial iterative type I PKSs. This review covers recent examples of iteratively used modular PKSs in bacteria. These non-canonical PKSs give rise to a large array of natural products with impressive structural diversity. The molecular mechanism behind the iterations is often unclear, presenting a new challenge to the rational engineering of these PKSs with the goal of generating new natural products. Structural elucidation of these synthase complexes and better understanding of potential PKS-PKS interactions as well as PKS-substrate recognition may provide new prospects and inspirations for the discovery and engineering of new bioactive polyketides. PMID- 26549239 TI - Lichens as natural sources of biotechnologically relevant bacteria. AB - The search for microorganisms from novel sources and in particular microbial symbioses represents a promising approach in biotechnology. In this context, lichens have increasingly become a subject of research in microbial biotechnology, particularly after the recognition that a diverse community of bacteria other than cyanobacteria is an additional partner to the traditionally recognized algae-fungus mutualism. Here, we review recent studies using culture dependent as well as culture-independent approaches showing that lichens can harbor diverse bacterial families known for the production of compounds of biotechnological interest and that several microorganisms isolated from lichens, in particular Actinobacteria and Cyanobacteria, can produce a number of bioactive compounds, many of them with biotechnological potential. PMID- 26549240 TI - The reproductive effort of Lepeophtheirus pectoralis (Copepoda: Caligidae): insights into the egg production strategy of parasitic copepods. AB - The reproductive effort of Lepeophtheirus pectoralis (Muller O. F., 1776), a caligid copepod, which is commonly found infecting the European flounder, Platichthys flesus (Linnaeus, 1758), is studied in detail for the first time. Seasonal variation in body dimensions and reproductive effort are analysed. Data for 120 ovigerous females, 30 from each season of the year, were considered in the analyses. Females were larger and produced a larger number of smaller eggs in winter, than during the summer. The relationship between egg number and egg size is similar to that recorded for other copepods exploiting fish hosts. Much of the recorded variation was also similar to that reported for a copepod parasitic on an invertebrate host, which suggests the possibility of a general trend in copepod reproduction. Overall, our results provide further support for the hypothesis that there is an alternation of summer and winter generations. PMID- 26549241 TI - Provider Opinions Regarding Expanding Access to Hormonal Contraception in Pharmacies. AB - PURPOSE: Expanding access to hormonal contraception may reduce the barrier created with the current prescription requirement. The goal of this study was to gain a better understanding of health care providers' opinions on expanding access to hormonal contraception (oral pill, transdermal patch, vaginal ring, and injectable) and the role of pharmacists as direct providers of this reproductive health service. METHODS: A voluntary, self-administered survey was distributed to participating national professional associations' physician and midlevel provider members who provide reproductive health services. Outcomes of providers' opinions on expanded access to hormonal contraception in pharmacies were analyzed by provider type (n = 482). FINDINGS: Almost three-quarters (74%) of the 482 providers surveyed, 76% of physicians and 70% of midlevels, were supportive of expanding access for the pill, patch, and ring contraceptives to include pharmacist-initiated access. Despite overall support for pharmacist-initiated access, more than 70% of respondents were concerned that expanded access would result in decreased reproductive health preventive screening. Slightly fewer providers supported or were neutral towards behind-the-counter (65% for pill/patch/ring, 55% injectable) and over-the-counter (47% for pill/patch/ring, 36% injectable) access than for pharmacist-initiated access. CONCLUSIONS: The majority of reproductive health providers support pharmacist-initiated access to the pill, patch, ring, and injectable contraceptives. There is some support for behind-the-counter and over-the-counter access. Provider concerns about lower rates of reproductive health preventive screenings and pharmacist training issues would need to be appropriately addressed along with any policy changes. PMID- 26549242 TI - Receipt of Prescription Opioids in a National Sample of Pregnant Veterans Receiving Veterans Health Administration Care. AB - BACKGROUND: A growing number of reproductive-age women veterans are returning from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). In 2010, 42% of women veterans receiving Veterans Health Administration (VHA) services were aged 18 to 45. Prescription opioid use has increased among all veterans over the past decade; however, exposure among pregnant veterans has not been examined. METHODS: We identified 2,331 women who delivered babies within the VHA system between 2001 and 2010. Delivery, opioid prescribing history, and demographic and health-related variables were obtained from a national database of veterans receiving VHA services. Receipt of an opioid prescription was defined as any filled VHA prescription for opioids in the 280-day pregnancy window before delivery. We developed a multivariable logistic regression model adjusted for sociodemographic, service-related, psychiatric diagnosis, and physical health variables to examine the odds of filling an opioid prescription during the pregnancy window. FINDINGS: Ten percent of pregnant veterans received VHA prescription opioids during their pregnancy window. Significant factors associated with opioid prescriptions included presence of any psychiatric diagnosis (adjusted odds ratio [aOR], 1.67; 95% CI, 1.24-2.26), diagnosis of back problems (aOR, 2.94; 95% CI, 1.92-4.49), or other nontraumatic joint disorders (aOR, 2.20; 95% CI, 1.36-3.58). CONCLUSIONS: This study suggests that a substantial proportion of women veterans received VHA prescriptions for opioids during pregnancy. Providers should be aware of the potential risks of prescription opioid use during pregnancy, assess for potential undertreatment of psychiatric diagnoses, and consider alternate pain management strategies when possible. PMID- 26549243 TI - Patient-centered Care in Maternity Services: A Critical Appraisal and Synthesis of the Literature. AB - BACKGROUND: Patient-centered care (PCC) has been recognized as a marker of quality in health service delivery. In policy documents, PCC is often used interchangeably with other models of care. There is a wide literature about PCC, but there is a lack of evidence about which model is the most appropriate for maternity services specifically. AIM: We sought to identify and critically appraise the literature to identify which definition of PCC is most relevant for maternity services. METHODS: The four-step approach used to identify definitions of PCC was to 1) search electronic databases using key terms (1995-2011), 2) cross-reference key papers, 3) search of specific journals, and 4) search the grey literature. Four papers and two books met our inclusion criteria. ANALYSIS: A four-criteria critical appraisal tool developed for the review was used to appraise the papers and books. MAIN RESULTS: From the six identified definitions, the Shaller's definition met the majority of the four criteria outlined and seems to be the most relevant to maternity services because it includes physiologic conditions as well as pathology, psychological aspects, a nonmedical approach to care, the greater involvement of family and friends, and strategies to implement PCC. CONCLUSION: This review highlights Shaller's definitions of PCC as the one that would be the most inclusive of all women using maternity services. Future research should concentrate on evaluating programs that support PCC in maternity services, and testing/validating this model of care. PMID- 26549244 TI - Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma. AB - Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)-challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA-induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA-challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium-activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose-dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway. PMID- 26549245 TI - Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model. AB - Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2MUg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture. PMID- 26549247 TI - Helpful and Useful. PMID- 26549246 TI - Joint dysfunction and functional decline in middle age myostatin null mice. AB - Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway. PMID- 26549248 TI - Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease. AB - The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations. PMID- 26549249 TI - Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). AB - BACKGROUND: In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis. OBJECTIVE: We sought to evaluate efficacy of apremilast in nail/scalp psoriasis in ESTEEM 1 and 2. METHODS: A total of 1255 patients were randomized (2:1) to apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score >=1) and moderate to very severe scalp (Scalp Physician Global Assessment score >=3) psoriasis at baseline. RESULTS: At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: -22.5% versus +6.5% (ESTEEM 1; P < .0001) and 29.0% versus -7.1% (ESTEEM 2; P = .0052). At week 16, apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P < .0001) and ScPGA response (Scalp Physician Global Assessment score 0 or 1) versus placebo (both studies P < .0001). Improvements were generally maintained over 52 weeks in patients with Psoriasis Area and Severity Index response at week 32. LIMITATIONS: Baseline randomization was not stratified for nail/scalp psoriasis. CONCLUSION: Apremilast reduces the severity of nail/scalp psoriasis. PMID- 26549250 TI - A nongrading histologic approach to Clark (dysplastic) nevi: A potential to decrease the excision rate. AB - BACKGROUND: Despite a lack of evidence that dysplastic nevi are precursors to melanoma, a large proportion of dermatologists continue to treat them as such. Emerging data suggest that histologic grading approach may result in many unnecessary excisions. OBJECTIVE: Using a nongrading approach to diagnosis of Clark/dysplastic nevi, the current study sought to define and determine the diagnostic uncertainty rate, and to report on the results of re-excisions of such lesions. METHODS: All melanocytic nevi submitted to an academic dermatopathology laboratory between January 1, 2007, and December 31, 2013, were categorized. The number of Clark nevi recommended for re-excision divided by the total number of Clark nevi was taken to be the diagnostic uncertainty rate. RESULTS: This nongrading approach resulted in an excision recommendation/diagnostic uncertainty rate of 11.1%. In 2% of the excised specimens, the diagnosis was changed to melanoma. LIMITATIONS: The study was performed at a single institution, and assigned diagnoses could not be verified other than by the diagnosing dermatopathologists. Lesions that were not submitted as re-excision specimens could have altered the results had they been available for evaluation. CONCLUSION: Compared with previously reported excision rates, the current study shows that the nongrading approach to Clark nevi results in a lower excision rate while still maintaining a low rate of change in diagnosis similar to the grading approach. PMID- 26549251 TI - Microneedling in skin of color: A review of uses and efficacy. AB - In ethnic skin, traditional skin resurfacing procedures such as dermabrasion, chemical peels, and laser therapy can be effective but can also be associated with prolonged recovery and risk of complications. These complications can include a higher risk of dyspigmentation and scarring, and unsatisfactory clinical outcomes. Microneedling is an evolving treatment technique for an expanding number of dermatologic conditions. Microneedling may offer a more advantageous safety profile, particularly in the skin-of-color population (Fitzpatrick skin types IV-VI), compared with more conventional resurfacing modalities. Thus far, it has been shown to be effective for a number of dermatologic conditions in this population, including scarring, melasma, melanosis, skin rejuvenation, acne vulgaris, and primary hyperhidrosis. This article aims to provide a comprehensive review of the literature regarding the efficacy and safety of microneedling in skin of color. PMID- 26549252 TI - Synthesis of 3-stannyl and 3-silyl propargyl phosphanes and the formation of a phosphinoallene. AB - The group 14 chloropropargyls R3EC = CCH2Cl (R3E = (n)Bu3Sn, Ph3Sn, Me2PhSi, (i)Pr3Si, (n)Pr3Si, (n)Bu3Si), obtained by a modified literature procedure, react with LiPPh2 to afford the novel propargyl phosphanes Ph2PCH2C = CER3 in high yield, as viscous oils; (Me3Si)2PCH2C = CSiPhMe2 is similarly obtained from LiP(SiMe3)2. In contrast, the reaction of PhC[triple bond, length as m dash]CCH2MgCl with ClP(NEt2)2 fails to produce a comparable propargyl phosphane, but generates preferentially (>70%) the novel phosphinoallene (Et2N)2PC(Ph) = C = CH2, which is characterised spectroscopically, and through its reaction with HCl. The coordination chemistry of representative phosphanes is explored with respect to platinum and palladium for the first time. PMID- 26549253 TI - Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity. AB - Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment) a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ~20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration. PMID- 26549254 TI - Securing Paternity by Mutilating Female Genitalia in Spiders. AB - Competition between males and their sperm over access to females and their eggs has resulted in manifold ways by which males try to secure paternity, ranging from physically guarding the female after mating to reducing her receptivity or her attractiveness to subsequent males by transferring manipulative substances or by mechanically sealing the female reproductive tract with a copulatory plug. Copulations may also result in internal damage of the female genitalia; however, this is not considered as a direct adaptation against sperm competition but as a collateral effect. Here, we present a drastic and direct mechanism for securing paternity: the removal of coupling structures on female genitalia by males. In the orb-weaving spider Larinia jeskovi males remove the scapus, a crucial coupling device on the female external genital region. Reconstruction of the coupling mechanism using micro-CT-scanned mating pairs revealed that several sclerites of the male genitalia interact to break off the scapus. Once it is removed, remating cannot occur due to mechanical coupling difficulties. In the field, male-inflicted genital damage is very prevalent since all female L. jeskovi were found to be mutilated at the end of the mating season. External genital mutilation is an overlooked but widely spread phenomenon since 80 additional spider species were found for which male genital manipulation can be suspected. Interlocking genitalia provide an evolutionary platform for the rapid evolution of this highly effective mechanism to secure paternity, and we suspect that other animal groups with interlocking genital structures might reveal similarly drastic male adaptations. PMID- 26549255 TI - Wild Vervet Monkeys Trade Tolerance and Specific Coalitionary Support for Grooming in Experimentally Induced Conflicts. AB - Grooming is a key social behavior in many primate species. Research has focused on three important aspects: the short- and long-term trading patterns of grooming for itself and/or for other commodities like tolerance or coalitionary support, the issue of whether exchanges are a convincing example for reciprocity, and what decision rules underlie trading. These issues remain largely unresolved due to the correlative nature of observational studies and the rarity of experimental studies. Here, we present a new experimental paradigm to address these questions in wild vervet monkeys (Chlorocebus pygerythrus). Adult females were first trained to approach a personal box, identifiable by unique color patterns, to access high-quality food. During the experiments, two boxes were placed next to each other to induce conflict through forced proximity. We found that while dominants were generally more tolerant toward bonded individuals, recent grooming increased tolerance independently of relationship quality. The latter result shows that vervet monkeys traded grooming for short-term tolerance, where dominants used a direct-reciprocity decision rule. In contrast, females invariably supported the higher-ranking opponent in a conflict, independently of who was the recent grooming partner. Nevertheless, recent grooming increased the probability that a female supported the partner during conflicts with a low ranking third party. Thus, females' decisions about coalitionary support seem to integrate information about the current social hierarchy with recent grooming events. In conclusion, decision rules underlying trading of grooming for other commodities involve a variety of timescales and factors. PMID- 26549256 TI - Alternate RASSF1 Transcripts Control SRC Activity, E-Cadherin Contacts, and YAP Mediated Invasion. AB - Tumor progression to invasive carcinoma is associated with activation of SRC family kinase (SRC, YES, FYN) activity and loss of cellular cohesion. The hippo pathway-regulated cofactor YAP1 supports the tumorigenicity of RAS mutations but requires both inactivation of hippo signaling and YES-mediated phosphorylation of YAP1 for oncogenic activity. Exactly how SRC kinases are activated and hippo signaling is lost in sporadic human malignancies remains unknown. Here, we provide evidence that hippo-mediated inhibition of YAP1 is lost upon promoter methylation of the RAS effector and hippo kinase scaffold RASSF1A. We find that RASSF1A promoter methylation reduces YAP phospho-S127, which derepresses YAP1, and actively supports YAP1 activation by switching RASSF1 transcription to the independently transcribed RASSF1C isoform that promotes Tyr kinase activity. Using affinity proteomics, proximity ligation, and real-time molecular visualization, we find that RASSF1C targets SRC/YES to epithelial cell-cell junctions and promotes tyrosine phosphorylation of E-cadherin, beta-catenin, and YAP1. RASSF1A restricts SRC activity, preventing motility, invasion, and tumorigenesis in vitro and in vivo, with epigenetic inactivation correlating with increased inhibitory pY527-SRC in breast tumors. These data imply that distinct RASSF1 isoforms have opposing functions, which provide a biomarker for YAP1 activation and explain correlations of RASSF1 methylation with advanced invasive disease in humans. The ablation of epithelial integrity together with subsequent YAP1 nuclear localization allows transcriptional activation of beta-catenin/TBX YAP/TEAD target genes, including Myc, and an invasive phenotype. These findings define gene transcript switching as a tumor suppressor mechanism under epigenetic control. PMID- 26549257 TI - Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters. AB - Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform, we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure. PMID- 26549258 TI - Inappropriate Neural Activity during a Sensitive Period in Embryogenesis Results in Persistent Seizure-like Behavior. AB - Maturation of neural circuits requires activity-dependent processes that underpin the emergence of appropriate behavior in the adult. It has been proposed that disruption of these events, during specific critical periods when they exert maximal influence, may lead to neurodevelopmental diseases, including epilepsy. However, complexity of neurocircuitry, coupled with the lack of information on network formation in mammals, makes it difficult to directly investigate this hypothesis. Alternative models, including the fruit fly Drosophila melanogaster, show remarkable similarities between experimental seizure-like activity and clinical phenotypes. In particular, a group of flies, termed bang-sensitive (bs) mutants have been extensively used to investigate the pathophysiological mechanisms underlying seizure. Seizure phenotype can be measured in larval stages using an electroshock assay, and this behavior in bs mutants is dramatically reduced following ingestion of typical anti-epileptic drugs (AEDs;). In this study we describe a critical period of embryonic development in Drosophila during which manipulation of neural activity is sufficient to significantly influence seizure behavior at postembryonic stages. We show that inhibition of elevated activity, characteristic of bs seizure models, during the critical period is sufficient to suppress seizure. By contrast, increasing neuronal excitation during the same period in wild-type (WT) is sufficient to permanently induce a seizure behavior. Further, we show that induction of seizure in WT correlates with functional alteration of motoneuron inputs that is a characteristic of bs mutants. Induction of seizure is rescued by prior administration of AEDs, opening a new perspective for early drug intervention in the treatment of genetic epilepsy. PMID- 26549259 TI - The Negative Association between Religiousness and Children's Altruism across the World. AB - Prosocial behaviors are ubiquitous across societies. They emerge early in ontogeny and are shaped by interactions between genes and culture. Over the course of middle childhood, sharing approaches equality in distribution. Since 5.8 billion humans, representing 84% of the worldwide population, identify as religious, religion is arguably one prevalent facet of culture that influences the development and expression of prosociality. While it is generally accepted that religion contours people's moral judgments and prosocial behavior, the relation between religiosity and morality is a contentious one. Here, we assessed altruism and third-party evaluation of scenarios depicting interpersonal harm in 1,170 children aged between 5 and 12 years in six countries (Canada, China, Jordan, Turkey, USA, and South Africa), the religiousness of their household, and parent-reported child empathy and sensitivity to justice. Across all countries, parents in religious households reported that their children expressed more empathy and sensitivity for justice in everyday life than non-religious parents. However, religiousness was inversely predictive of children's altruism and positively correlated with their punitive tendencies. Together these results reveal the similarity across countries in how religion negatively influences children's altruism, challenging the view that religiosity facilitates prosocial behavior. PMID- 26549260 TI - Cyp27c1 Red-Shifts the Spectral Sensitivity of Photoreceptors by Converting Vitamin A1 into A2. AB - Some vertebrate species have evolved means of extending their visual sensitivity beyond the range of human vision. One mechanism of enhancing sensitivity to long wavelength light is to replace the 11-cis retinal chromophore in photopigments with 11-cis 3,4-didehydroretinal. Despite over a century of research on this topic, the enzymatic basis of this perceptual switch remains unknown. Here, we show that a cytochrome P450 family member, Cyp27c1, mediates this switch by converting vitamin A1 (the precursor of 11-cis retinal) into vitamin A2 (the precursor of 11-cis 3,4-didehydroretinal). Knockout of cyp27c1 in zebrafish abrogates production of vitamin A2, eliminating the animal's ability to red-shift its photoreceptor spectral sensitivity and reducing its ability to see and respond to near-infrared light. Thus, the expression of a single enzyme mediates dynamic spectral tuning of the entire visual system by controlling the balance of vitamin A1 and A2 in the eye. PMID- 26549261 TI - Memory Formation in Tritonia via Recruitment of Variably Committed Neurons. AB - Prior studies have found that functional networks can rapidly add neurons as they build short-term memories, yet little is known about the principles underlying this process. Using voltage-sensitive dye imaging, we found that short-term sensitization of Tritonia's swim motor program involves rapid expansion of the number of participating neurons. Tracking neurons across trials revealed that this involves the conversion of recently discovered variably participating neurons to reliable status. Further, we identify a candidate serotonergic cellular mechanism mediating this process. Our findings reveal a new mechanism for memory formation, involving recruitment of pre-positioned, variably committed neurons into memory networks. This represents a shift from the field's long-term focus on synaptic plasticity, toward a view that certain neurons have characteristics that predispose them to join networks with learning. PMID- 26549262 TI - Dorsal and Ventral Pathways for Prosody. AB - Our vocal tone--the prosody--contributes a lot to the meaning of speech beyond the actual words. Indeed, the hesitant tone of a "yes" may be more telling than its affirmative lexical meaning. The human brain contains dorsal and ventral processing streams in the left hemisphere that underlie core linguistic abilities such as phonology, syntax, and semantics. Whether or not prosody--a reportedly right-hemispheric faculty--involves analogous processing streams is a matter of debate. Functional connectivity studies on prosody leave no doubt about the existence of such streams, but opinions diverge on whether information travels along dorsal or ventral pathways. Here we show, with a novel paradigm using audio morphing combined with multimodal neuroimaging and brain stimulation, that prosody perception takes dual routes along dorsal and ventral pathways in the right hemisphere. In experiment 1, categorization of speech stimuli that gradually varied in their prosodic pitch contour (between statement and question) involved (1) an auditory ventral pathway along the superior temporal lobe and (2) auditory-motor dorsal pathways connecting posterior temporal and inferior frontal/premotor areas. In experiment 2, inhibitory stimulation of right premotor cortex as a key node of the dorsal stream decreased participants' performance in prosody categorization, arguing for a motor involvement in prosody perception. These data draw a dual-stream picture of prosodic processing that parallels the established left-hemispheric multi-stream architecture of language, but with relative rightward asymmetry. PMID- 26549263 TI - Spiritual care as perceived by Lithuanian student nurses and nurse educators: A national survey. AB - BACKGROUND: Political restrictions during 50years of Soviet occupation discouraged expressions of spirituality among Lithuanians. THE AIM: The aim of this paper is to describe Lithuanian nursing educators' and students' perception of spiritual care in a post-Soviet context. DESIGN AND SETTINGS: This cross sectional study was carried out among student nurses and nursing educators at three universities and six colleges in Lithuania. PARTICIPANTS AND METHODS: The questionnaire developed by Scott (1959) and supplemented by Martin Johnson (1983) was distributed to 316 nursing students in the 3rd and 4th years of studies and 92 nurse educators (N=408). RESULTS: Student nurses and their educators rated general and professional values of religiousness equally; although students tended to dislike atheistic behavior more than educators. Four main categories associated with perceptions of spirituality in nursing care emerged from the student nurses: attributes of spiritual care, advantages of spiritual care, religiousness in spiritual care, and nurse-patient collaboration and communication. Themes from nurse educators paralleled the same first three themes but not the last one. CONCLUSIONS: Student nurses and nurse educators acknowledged the importance of spiritual care for patients as well as for care providers - nurses. In many cases spiritual care was defined by nursing students and nurse educators as faith and religiousness. Being a religious person, both for students and educators, or having spiritual aspects in students' personal lives influenced the perception of religious reflection. PMID- 26549264 TI - I-Kiribati nursing graduates experience of transition from university to residential aged care facilities in Australia. AB - OBJECTIVE: To explore the experience of international nursing graduates from Kiribati transitioning into practice in RACFs, upon completion of their bachelor of nursing degree in Australia. DESIGN: This study used an interpretive phenomenology design with two focus groups. A thematic analysis of the transcripts from the focus groups generated themes relating to the graduates personal journey through transition. SETTING: This study was conducted with graduates working in residential aged care facilities [RACF]. SUBJECTS: I Kiribati nursing graduates (N=6) who have been practicing for 1year in RACF. RESULTS: The experience of transition for the I-Kiribati graduates related to challenges faced during this time. Three themes were developed from the analysis: being unsure of expectations, understanding responsibilities of practice, and stepping up to the RN role. The influence of culture was apparent within the three themes. CONCLUSION: Overall, the transition to RACFs for the participants was difficult; however, students described increased confidence to work through professional and cultural challenges. They became more reliant on their own knowledge and skills as they matured as practitioners. Recommendations for improving the transition experience include transitional support and educational workshops related specifically to working in RACF. Tailoring workshops to the specific needs of international graduate nurses would assist their transition in relation to cultural differences. PMID- 26549265 TI - Resilience in nursing students: An integrative review. AB - OBJECTIVE: The aim of this integrative review was to investigate the state of knowledge on resilience in nursing students. Specifically the authors sought to define and describe the concept, and identify factors that affect and evaluate strategies to promote resilience in nursing students. DESIGN: Integrative literature review. DATA SOURCES: Cumulative Index to Nursing and Allied Health (CINHAL), Education Resources Information Center (ERIC) and PsychINFO electronic databases were searched for publications between 1990 and 2014. Search terms included resilience, student, nurse, nursing student, hardiness, emotional resilience, research, resili*, and nurse*. REVIEW METHODS: Whittemore and Knafl's integrative approach was utilized to conduct the methodological review. Each article was assessed with an appraisal tool. RESULTS: The search resulted in the inclusion of nine articles. The majority of the literature utilized definitions of resilience from the discipline of psychology. One exception was a definition developed within nursing specific to nursing students. Factors that affect resilience were grouped into three themes: support, time, and empowerment. Strategies to promote resilience in nursing students were found in three of the nine articles, but their methods and findings were disparate. CONCLUSIONS: This review provides information about the concept of resilience in nursing students. Faculty awareness of the importance of resilience in nursing students can better prepare students for the role of the professional nurse. Support from family, friends and faculty impact a student's resilience. Through closely working with students in advisement, the clinical arena and the classroom faculty can promote resilience. PMID- 26549266 TI - High-Fidelity Contrast Reaction Simulation Training: Performance Comparison of Faculty, Fellows, and Residents. AB - PURPOSE: Reactions to contrast material are uncommon in diagnostic radiology, and vary in clinical presentation from urticaria to life-threatening anaphylaxis. Prior studies have demonstrated a high error rate in contrast reaction management, with smaller studies using simulation demonstrating variable data on effectiveness. We sought to assess the effectiveness of high-fidelity simulation in teaching contrast reaction management for residents, fellows, and attendings. METHODS: A 20-question multiple-choice test assessing contrast reaction knowledge, with Likert-scale questions assessing subjective comfort levels of management of contrast reactions, was created. Three simulation scenarios that represented a moderate reaction, a severe reaction, and a contrast reaction mimic were completed in a one-hour period in a simulation laboratory. All participants completed a pretest and a posttest at one month. A six-month delayed posttest was given, but was optional for all participants. RESULTS: A total of 150 radiologists participated (residents = 52; fellows = 24; faculty = 74) in the pretest and posttest; and 105 participants completed the delayed posttest (residents = 31; fellows = 17; faculty = 57). A statistically significant increase was found in the one-month posttest (P < .00001) and the six-month posttest scores (P < .00001) and Likert scores (P < .001) assessing comfort level in managing all contrast reactions, compared with the pretest. Test scores and comfort level for moderate and severe reactions significantly decreased at six months, compared with the one-month posttest (P < .05). CONCLUSIONS: High fidelity simulation is an effective learning tool, allowing practice of "high acuity" situation management in a nonthreatening environment; the simulation training resulted in significant improvement in test scores, as well as an increase in subjective comfort in management of reactions, across all levels of training. A six-month refresher course is suggested, to maintain knowledge and comfort level in contrast reaction management. PMID- 26549267 TI - Preface. PMID- 26549268 TI - Prescription patterns of traditional Chinese medicine for peptic ulcer disease in Taiwan: A nationwide population-based study. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer disease is a common digestive disease. There is a lack of large-scale survey on the use of traditional Chinese medicine (TCM) for the treatment of peptic ulcer disease. This study aimed to investigate the utilization of TCM for the treatment of peptic ulcer disease in Taiwan. MATERIALS AND METHODS: We analyzed a random sample comprised of one million individuals with newly diagnosed peptic ulcer disease between 2001 and 2010 from the National Health Insurance Research Database in Taiwan. Demographic characteristics and TCM usage, including Chinese herbal formulas and the single herbs prescribed for patients with peptic ulcer disease, were analyzed. RESULTS: A total of 96,624 newly diagnosed subjects with peptic ulcer disease were included. 14,983 (15.5%) patients were TCM users. People residing in highly urbanized areas, younger people and female (compared with male) were more likely to use TCM. With regard to the comorbidities, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus and liver cirrhosis and stroke. The average time between onset of peptic ulcer disease and the first visit to a TCM clinic was 4.7 months. Majority of the patients (n=14,449; 96.4%) received only Chinese herbal remedies. The most frequently prescribed Chinese herbal formula and single herb was Ban-Xia-Xie-Xin Tang (Pinelliae Decoction to Drain the Epigastrium) and Hai-Piao-Xiao (Os Sepiae), respectively. The core pattern analysis showed that combination of Ban Xia-Xie-Xin-Tang, Hai-Piao-Xiao (Os Sepiae), Yan-Hu-Suo (Rhizoma Corydalis), Bei Mu (Bulbus Fritillariae Thunbergii) and Chuan-Lian-Zi (Fructus Toosendan) was most frequently used for peptic ulcer disease. CONCLUSIONS: Our study identified the core prescription patterns of TCM for patients with peptic ulcer disease in Taiwan. Further basic and clinical studies are necessary to elucidate the efficacy and mechanisms. PMID- 26549269 TI - Studies of the effect of grasshopper abdominal secretion on wound healing with the use of murine model. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Grasshopper, belonging to Chorthippus sp., is a widespread insect inhabiting Polish territory. According to folk knowledge and folk tales, the grasshopper abdominal secretion was used by villagers of Central and South-West Poland as a natural drug accelerating the wound healing process. AIM OF THE STUDY: In the reported study the hypothesis about beneficial properties of grasshopper abdominal secretion on hard to heal wounds was verified. MATERIALS AND METHODS: The study was carried out with the use of a murine model (mice C57BL/6). In order to verify the beneficial properties of grasshopper abdominal secretion, the wounds of 8mm in diameter were formed on one side of each tested mouse. The influence of ethanolic extract of insects' secretion on healing process was evaluated in comparison to ethanolic solution of allantoin and 30% aqueous solution of ethanol (medium). The observation was carried out over a 14 day period. Finally the statistical analysis (ANOVA) was carried out to highlight the differences in wound healing rate between applied preparations. Moreover, qualitative composition of grasshoppers' secretion was studied with the use of GC/MS technique. RESULTS: During the first three days of observation, wounds treated with allantoin were healed with higher efficiency in comparison to ethanol and insect secretion preparations. The trend of healing changed from the 4th day of observation. Wounds treated with grasshoppers' abdominal secretion were closuring faster than wounds treated with allantoin or ethanol. In this part of observation, in the case of allantoin and ethanol application, the wound healing efficiency was similar. Since the 9th day of experiment the measurement of wounds size was problematic, due to crust formation. Finally at the 14th day of the study, wounds were totally healed. Morphological study enabled to observe all the phases of healing. In the 5th and 8th day, the infiltration of neutrophils and mononuclear cells in dermis was observed, which is characteristic for inflammatory phase of wound healing. On the 8th day of experiments, granulation of the tissue was clearly observed in the tested groups. Reepithelialization phase was observed from the 5th to 14th day, when the wound was totally healed. The analytical approach enabled to identify 38 compounds of hydrophobic or hydrophilic character. Among them, 6 amino acids, 14 organic acids and their derivatives, one sterol, 4 hydrocarbons, 5 carbohydrates, 2 inorganic acids, 4 alcohols, one diamine and one nucleoside were identified. CONCLUSION: The obtained results enabled to recognize the composition of grasshopper abdominal secretion. Some of the identified compounds possess therapeutic properties described in the literature. The performed in vivo study proved that application of insects secretion accelerates the healing process. The obtained results positively verified the scientific hypothesis based on ethnopharmacological premises about the beneficial properties of grasshopper abdominal secretion on wound healing process. PMID- 26549270 TI - Antimutagenicity and induction of antioxidant defense by flavonoid rich extract of Myrcia bella Cambess. in normal and tumor gastric cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The Brazilian "Cerrado" is an important source of natural products, such as Myrcia bella Cambess (MB, also known as "mercurinho"). MB leaves are popularly used for the treatment of diabetes and gastrointestinal disorders; however, only its hypoglycemic activity has been experimentally described. AIM OF THE STUDY: Because MB is used to treat gastrointestinal disorders, the present study characterized biological activities of hydroalcoholic MB extract in human normal and tumor gastric cells. MATERIALS AND METHODS: Cytotoxic, antiproliferative, genotoxic and protective effects were evaluated, as well as the effects of the MB extract on gene expression. RESULTS: The MB extract induced cytotoxicity in tumor cells at lower concentrations compared with normal cells as assessed by the MTT assay. Moreover, the MB extract induced necrosis based on acridine orange/ethidium bromide staining. An antiproliferative effect was evidenced through an arrest in the G2/M phase detected by flow cytometry and a decrease in the nuclear division index using the cytokinesis-block micronucleus cytome assay. Cells treated with MB extract combined with doxorubicin (DXR) showed increased NUBDs, which may be related to the gene amplification of CCND1. Antimutagenic effects were also observed and may be associated with the antioxidant activities detected using the CM-H2DCFDA probe. CONCLUSIONS: Our findings showed the following: (a) high concentrations of MB induced cytotoxicity and cell death by necrosis; (b) its antiproliferative effect was associated with G2/M arrest; and (c) its antioxidant activity could be responsible for the observed antimutagenic effects and for protective effects against gastrointestinal disorders previously described to MB. Although these effects are not specific to normal or tumor cells, they provide a panel of biological activities for further exploration. PMID- 26549271 TI - Review: African medicinal plants with wound healing properties. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wounds of various types including injuries, cuts, pressure, burns, diabetic, gastric and duodenal ulcers continue to have severe socio-economic impact on the cost of health care to patients, family and health care institutions in both developing and developed countries. However, most people in the developing countries, especially Africa, depend on herbal remedies for effective treatment of wounds. Various in vitro and in vivo parameters are used for the evaluation of the functional activity of medicinal plants by using extracts, fractions and isolated compounds. The aim of the review is to identify African medicinal plants with wound healing properties within the last two decades. MATERIALS AND METHODS: Electronic databases such as PubMed, Scifinder((r)) and Google Scholar were used to search and filter for African medicinal plants with wound healing activity. The methods employed in the evaluation of wound healing activity of these African medicinal plants comprise both in vivo and in vitro models. In vivo wound models such as excision, incision, dead space and burn wound model are commonly employed in assessing the rate of wound closure (contraction), tensile strength or breaking strength determination, antioxidant and antimicrobial activities, hydroxyproline content assay and histological investigations including epithelialisation, collagen synthesis, and granulation tissue formation. In in vitro studies, single cell systems are mostly used to study proliferation and differentiation of dermal fibroblasts and keratinocytes by monitoring typical differentiation markers like collagen and keratin. RESULTS: In this study, 61 plants belonging to 36 families with scientifically demonstrated or reported wound healing properties were reviewed. Various plant parts including leaves, fruits, stem bark and root extracts of the plants are used in the evaluation of plants for wound healing activities. CONCLUSION: Although, a variety of medicinal plants for wound healing can be found in literature, there is a need for the isolation and characterization of the bioactive compounds responsible for the wound healing properties. Also, cytotoxicity studies should be performed on the promising agents or bioactive fractions or extracts. PMID- 26549272 TI - Proliferative effect of plants used for wound healing in Rio Grande do Sul state, Brazil. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wounds are normally resolved in a few days, but chronic wounds represent a major burden because of economic and social factors. Thereby, the search for new agents is ongoing and natural products become a great target. Also, Brazil as a consumer of herbal medicines with rich social diversity is promising for ethnopharmacological studies. AIMS OF THE STUDY: The study aims to find the plants popularly used for wound healing purposes in Rio Grande do Sul state, and test the traditional knowledge through an in vitro screening. MATERIALS AND METHODS: Ethnobotanical studies from state of Rio Grande do Sul were analyzed to find the most used plants to treat wounds. The selected species were collected, identified and ethanolic and aqueous extracts were prepared. After, proliferative capacity was accessed by MTT assay in a keratinocyte cell line (HaCaT). RESULTS: The survey comprehended almost all state regions and led to 117 plant species from 85 genera, from which 14 were selected for in vitro testing. Aqueous extracts from Achyrocline satureioides DC Lam., Matricaria recutita L., Melia azedarach L. and Mirabilis jalapa L. demonstrated the ability to stimulate keratinocyte growth up to 120% in concentrations of 25 ug/mL and 50 ug/mL. The ethanolic extract of A. satureioides was able to stimulate keratinocyte and fibroblast proliferation on the lower concentration tested, 1 ug/mL, being the most promising species. CONCLUSIONS: The traditional knowledge collected from the ethnobotanical studies was accessed by in vitro investigation and extracts from Achyrocline satureioides, Matricaria recutita, Melia azedarach and Mirabilis jalapa can influence positively cell proliferation. PMID- 26549273 TI - Protection of testis through antioxidant action of Mallotus roxburghianus in alloxan-induced diabetic rat model. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mallotus roxburghianus is used for its antihyperglycaemic properties in Southeast Asia especially in Northeast India (Mizoram) and is also recognized in traditional medicine. About 90% of diabetic patients have been associated with reproductive impairments. The primary aim of this investigation is to examine the effects of diabetes on oxidative stress, steroidogenesis, histopathology, proliferation of germ cells with proliferative cell nuclear antigen (PCNA) and antioxidant status, and alleviative effect of M. roxburghianus on the testis dysfunction. MATERIALS AND METHODS: Methanolic leaf extract of M. roxburghianus was given to male albino Wistar rats by oral gavage to study the acute toxicity. Phyto-chemical composition of the methanol extract of M. roxburghianus was analyzed by GC-MS. Male Wistar rats were divided into six groups with seven animals in each group: untreated control; M. roxburghianus methanolic extract control (MRME, 400mg/kg); Alloxan diabetic control group (150 mg/kg); diabetic with 100mg/kg MRME treatment; diabetic with 400mg/kg MRME treatment; and diabetic with glibenclamide (0.1mg/kg) treatment. Diabetes was induced by a single intraperitoneal injection of 150 mg/kg alloxan and was confirmed by testing fasting plasma blood glucose levels 5 days after injection. MRME was administered orally for 28 days. Body and testis weights, serum testosterone, testis malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione S transferase (GST) and protein levels were measured, and testis tissue was examined histopathologically and immunohistochemically (PCNA). RESULTS: No sign of mortality and organ toxicity was observed up to 3000 mg/kg in acute toxicity assay of MRME and inferred to be non-toxic and safe. Bergenin and betulinic acid are the major components of MRME with many biological activities. MRME treatment rendered significant increases in body weight, testis weight, testes-body weight ratio, down regulated the MDA levels, reduced the degeneration and disruption of seminiferous tubule structure, restored the antioxidant enzymes and serum testosterone levels, increased the PCNA activities and attenuated the testes injury. CONCLUSION: MRME treatment to diabetic rats improves diabetes induced oxidative damage in testis as well as provides protection to testis. Phenols (Bergenin) and terpenes (Betulinic acid) were the main compounds of MRME that show antioxidant and antidiabetic activities and indeed validated its traditional use in the management of diabetes related testicular impairment. PMID- 26549274 TI - Development, differentiation, and vascular components of subcutaneous and intrahepatic Hepa129 tumors in a mouse model of hepatocellular carcinoma. AB - Tumor models in mice offer opportunities for understanding tumor formation and development of therapeutic treatments for hepatocellular carcinoma. In this study, subcutaneous or intra-hepatic Hepa129 tumors were established in C3H mice. Tumor growth was determined by daily measurements of subcutaneous tumors and post mortem studies of subcutaneous and intrahepatic tumors. Administration of Edu was used to determine cell generation dates of tumor cells. Immunohistochemistry with antibodies directed at CD31 or CD34, and intravenous injection of labeled tomato lectin revealed tumor vasculature. Tissue sections also were processed for immunohistochemistry using a panel of antibodies to proteoglycans. Comparison of Edu labeled cells with immunoreactivity allowed determination of development and differentiation of tumor cells after cell generation. Subcutaneous and intrahepatic tumors displayed similar growth over 3 weeks. Immunohistochemistry showed strong labeling for glypican-3, 9BA12, and chondroitin sulfate of tumors in both loci, while normal liver was negative. Tumor regions containing Edu labeled cells did not show significant immunohistochemical labeling for the tumor markers until 2-3 days after Edu treatment; overlap of Edu labeled cells and immunohistochemically labeled tumor regions appeared to reach a maximum at 5 days after Edu treatment. Ectopic subcutaneous tumors displayed vascular ingrowth as the tumor cells expressed immunocytochemical markers; subcutaneous tumors displayed significantly more vascular elements than did intrahepatic tumors. PMID- 26549275 TI - Pancreatic exocrine insufficiency in type 1 and type 2 diabetics of Indian origin. AB - BACKGROUND: Pancreatic exocrine insufficiency has been frequently described in both type 1 and type 2 diabetes. Fecal elastase test has been demonstrated to have good correlation with direct tests for exocrine function, especially in moderate to severe cases. There are no data on the prevalence of pancreatic exocrine insufficiency in Indian patients with diabetes utilizing FEC concentrations. The objective of our study is to evaluate the prevalence of pancreatic exocrine insufficiency (PEI) in type 1 and type 2 diabetes and study the impact of PEI on glycemic control and metabolic parameters in diabetes. METHODS AND MATERIALS: We conducted a cross sectional study on 89 T1D, 95 T2D patients and 90 healthy controls. Biochemical parameters including FBS, HbA1c, serum albumin and serum calcium were estimated. Fecal elastase concentrations (FEC) were estimated by ELISA. Patients with FEC <200 MUg/g were considered to have pancreatic exocrine insufficiency. RESULTS: The prevalence of PEI was 31.4% in T1D, 29.4% in T2D and 4.4% in controls (P < 0.01). A significant negative correlation was observed between FEC levels and, both FBS and HbA1c in diabetic patients. There was also a significant positive correlation between BMI and FEC. There was no significant association between low FEC and other biochemical parameters. CONCLUSION: Nearly one third of patients with both T1D and T2D showed evidence of impaired exocrine function utilizing FEC test. Presence of PEI correlated with lower BMI and higher HbA1c. PMID- 26549277 TI - Investigating the Islamic Perspective on Homosexuality. AB - In his 2006 article in the Journal of the Islamic Medical Association of North America (JIMA), Dr. Ahmed qualified the predominant psychiatric view on homosexuality by recourse to opinions prevalent within reparative therapy circles. Conservative Muslim thinkers, online counselors, and other professionals continue to hold opinions similar to those delineated by Dr. Ahmed in his journal article. We use his article as a focal point to critique the general opinions upheld by conservative Muslim thinkers by alluding to the harms associated with reparative therapy and by rejecting the unreasonable prescription of permanent celibacy. We critique Dr. Ahmed's association of homosexuality with mental health issues, fatal diseases, alcoholism, and illicit sexual intercourse. Investigating the Muslim tradition, we encourage conservative Muslim leaders to facilitate Muslim gays and lesbians in their legitimate human need for intimacy, affection, and companionship. PMID- 26549276 TI - Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study. AB - INTRODUCTION: Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). METHODS: This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ICUs. The patient groups established according to the high-protein formula received were: group A, new-generation diabetes-specific formula; group B, standard control formula; group C, control diabetes-specific formula. Inclusion criteria were: expected enteral nutrition >=5 days, MV, baseline glucose >126 mg/dL on admission or >200 mg/dL in the first 48 h. Exclusion criteria were: APACHE II <=10, insulin-dependent diabetes, renal or hepatic failure, treatment with corticosteroids, immunosuppressants or lipid lowering drugs and body mass index >=40 kg/m(2). The targeted glucose level was 110-150 mg/dL. Glycemic variability was calculated as the standard deviation, glycemic lability index and coefficient of variation. Acquired infections were recorded using published consensus criteria for critically ill patients. Data analysis was on an intention-to-treat basis. RESULTS: Over a 2-year period, 157 patients were consecutively enrolled (A 52, B 53 and C 52). Compared with the standard control formula, the new formula gave rise to lower insulin requirement (19.1 +/- 13.1 vs. 23.7 +/- 40.1 IU/day, p <0.05), plasma glucose (138.6 +/- 39.1 vs. 146.1 +/- 49.9 mg/dL, p <0.01) and capillary blood glucose (146.1 +/- 45.8 vs. 155.3 +/- 63.6 mg/dL, p <0.001). Compared with the control diabetes-specific formula, only capillary glucose levels were significantly reduced (146.1 +/- 45.8 vs. 150.1 +/- 41.9, p <0.01). Both specific formulas reduced capillary glucose on ICU day 1 (p <0.01), glucose variability in the first week (p <0.05), and incidences of ventilator-associated tracheobronchitis (p <0.01) or pneumonia (p <0.05) compared with the standard formula. No effects of the nutrition formula were produced on hospital stay or mortality. CONCLUSIONS: In these high-risk ICU patients, both diabetes-specific formulas lowered insulin requirements, improved glycemic control and reduced the risk of acquired infections relative to the standard formula. Compared with the control-specific formula, the new-generation formula also improved capillary glycemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT1233726 . PMID- 26549278 TI - When Middle Really Means "Top" or "Bottom": An Analysis of the 16PF5 Using Bock's Nominal Response Model. AB - When self-report items with a Likert-type scale include a middle response option (e.g., Unsure, Neither agree nor disagree, or ?), this middle option is assumed to measure a level of the trait intermediate between the high and low response categories. In this study, we tested this assumption in the 16 Personality Factor Questionnaire, Version 5 (16PF5) by fitting Bock's nominal response model in the U.S. and UK standardization samples of the 16PF5. We found that in many cases, the middle option was indicative of higher levels of the latent trait than the ostensibly highest response option. In certain other cases, it was indicative of lower levels of the latent trait than the ostensibly lowest response option. This undermines the use of a simple successive integer scoring scheme where responses in adjacent response categories are assigned scores of 0, 1, and 2. Recommendations for alternative scoring schemes are provided. Results also suggested that certain personality traits, especially neurotic traits, are associated with a tendency toward selecting the middle option. PMID- 26549279 TI - Java project on periodontal diseases: effect of vitamin C/calcium threonate/citrus flavonoids supplementation on periodontal pathogens, CRP and HbA1c. AB - OBJECTIVE: To assess in a periodontally diseased rural population deprived from regular dental care and having poor dietary conditions, the effect of vitamin C/calcium threonate/citrus flavonoids (VitC/Ca/Fl) supplementation on subgingival microbiota and plasma levels of vitamin C, HbA1c and hsCRP. MATERIAL & METHODS: The study population consisted of 98 subjects who previously participated in a prospective study on the natural history of periodontitis. Participants were instructed to consume one tablet/day containing 200 mg Ester C((r)) calcium ascorbate, 25 mg calcium threonate and 100 mg citrus flavonoids for 90 days. Following parameters were evaluated: prevalence/amount of seven traditional periodontal pathogens, cytomegalovirus, Epstein-Barr virus (EBV); and plasma levels of vitamin C, HbA1c and hsCRP. RESULTS: After VitC/Ca/Fl supplementation, 100% of subjects showed normal plasma vitamin C values compared to 55% before. At baseline, 48% of subjects harboured Aggregatibacter actinomycetemcomitans, >97% the other periodontal pathogens and 73% EBV. Supplementation with VitC/Ca/F reduced the subgingival load of all studied bacteria (p-values: 0.014-0.0001) and EBV (p < 0.0001) substantially in all initially positive subjects. Plasma levels of HbA1c and hsCRP dropped in all subjects (p < 0.0001). CONCLUSION: This uncontrolled study suggested that supplemental VitC/Ca/Fl may be helpful in reducing subgingival numbers of periodontal pathogens and EBV, and promoting systemic health. PMID- 26549280 TI - Exploring Prospective Predictors of Illicit Drug-Toxicity Deaths: Evidence From the General Social Survey. AB - BACKGROUND: This study was based on over 30,000 U.S. respondents who completed General Social Surveys between 1978 and 2002. AIMS: We approached these respondents prospectively, comparing and contrasting the responses of those who subsequently died from drug-poisonings (N = 135) with all respondents who were still living, N = 23,559. METHOD: We employed cross-tabulation and logistic regression analyses to test for statistically significant differences between drug-poisoning death casualties and all living respondents. RESULTS: Consistent with past research findings, younger males were over-represented among drug death casualties. Also consistent with past studies, drug casualties showed evidence of perceiving themselves as socially marginalized in comparison to living respondents: More reported themselves in poorer health, as having been sexual minority members during the last 5 years, as having spent their younger years in homes where parents' marriages disrupted, with fewer owning homes and feeling less satisfied about their financial situations. CONCLUSIONS: These exploratory findings obtained from a general population survey reinforce findings from clinical studies and help advance clinical assessments of potential at-risk individuals who might be identified sooner, lest they succumb to future fatal drug poisonings. PMID- 26549281 TI - Impact of the Presence of Chronic Total Occlusion in a Non-Infarct-Related Coronary Artery in Acute Myocardial Infarction Patients. AB - Chronic total occlusion (CTO) in a non-infarcted-related artery was reported to worsen immediate clinical outcome in acute myocardial infarction (AMI) patients. However, the prognosis of such patients with preserved left ventricular function after successful primary percutaneous coronary intervention (PCI) has not yet been clarified. The aim of the present study was to evaluate whether the presence of CTO contributes to a worse prognosis even in patients with preserved left ventricular function after primary PCI.We retrospectively analyzed 353 consecutive patients with acute myocardial infarction, whose left ventricular ejection fraction (LVEF) was not less than 40% in the echocardiography performed 1 day after primary PCI. We divided the patients into two groups according to the presence (n = 25) or absence (n = 328) of CTO in the non-infarct-related coronary artery, and compared the clinical outcome of patients between the two groups.The LVEF estimated by echocardiography after primary PCI was similar between patients with and without CTO (55.1 +/- 8.6% versus 58.0 +/- 9.4%; P = 0.07). The peak creatine kinase value was also similar between the two groups (1539 versus 1921 U/L; P = 0.33); however, CTO patients were significantly more likely to undergo intra-aortic balloon pumping (56.0% versus 12.5%; P < 0.001) during primary PCI, and 30-day mortality was significantly higher in CTO patients (12.0% versus 0.9%; P < 0.001). By multivariate analysis, cardiogenic shock at arrival was significantly correlated with 30-day mortality.Even though the LVEF of AMI patients with CTO was preserved after successful PCI, a high mortality rate was observed. PMID- 26549282 TI - Assessment of Efficacy and Necessity of Routine Defibrillation Threshold Testing in Patients Undergoing Implantable Cardioverter-Defibrillator (ICD) Implantation. AB - Defibrillation threshold (DFT) testing is performed routinely in patients undergoing implantable cardioverter-defibrillator (ICD) implantation to verify the ability of the ICD to terminate ventricular fibrillation (VF). However, neither the efficacy nor the safety of DFT testing has been proven; thus, the necessity of such testing is controversial. We conducted a retrospective study of the efficacy of DFT testing, particularly with respect to long-term outcomes of ICD implantation.The study included 150 patients (125 men, 25 women, aged 59.0 +/ 17.6 years) who underwent ICD or cardiac resynchronization therapy defibrillator implantation, with (n = 73) or without (n = 77) intraoperative DFT testing, between June 1996 and September 2007. VF was induced by delivery of a T-wave shock, and a 20-25-J shock was then delivered. If the 20-25-J shock failed to terminate VF, 30 J was delivered. We assessed whether undersensed VF events occurred during DFT testing and/or during patient follow-up and checked for any association between undersensing and delayed shock delivery. During DFT testing, fine VF was sensed, and shocks were delivered in a timely manner. Nevertheless, 2 patients in the DFT testing group died from VF within 3 years after device implantation.DFT testing, in comparison to non-DFT testing, appeared to have no influence on the long-term outcomes of our patients, suggesting that DFT testing at the time of ICD implantation is limited. PMID- 26549283 TI - Dramatic Response to Cardiac Resynchronization Therapy With AV Delay Optimization in Narrow QRS Heart Failure. AB - Cardiac resynchronization therapy (CRT) has been shown to be effective for heart failure. However, as outlined in the AHA/ACC/HRS Appropriate Use Criteria, CRT is not strongly recommended for patients with a narrow QRS complex. We describe a case of dilated cardiomyopathy and narrow QRS complex in which we obtained a dramatic response to CRT by optimizing the atrioventricular (AV) delay. The patient was a 61-year-old man with intractable heart failure. Echocardiography showed a low ejection fraction of 22% but no dyssynchrony. Because he had been hospitalized many times for congestive heart failure despite beta-blocker and diuretic treatment, we decided to use CRT. However, after implantation of the CRT device, the QRS complex widened abnormally, and his symptoms worsened. He was re admitted 2 months after CRT implantation. We examined the pacemaker status and optimized the AV delay to obtain a "narrow" QRS complex. The patient's condition improved dramatically after the AV delay optimization. His clinical status has been good, and there has been no subsequent hospitalization. Our case points to the effectiveness of CRT in patients with a narrow QRS complex and to the importance of AV optimization for successful CRT. PMID- 26549284 TI - Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy. AB - Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC. PMID- 26549285 TI - How Should We Treat Early Post-Transplant Lymphoproliferative Disease After Heart Transplantation? AB - Although post-transplant lymphoproliferative disease (PTLD) is one of the major fatal complications encountered several years after heart transplant (HTx), little is known about early-PTLD emerging within the first year. We here describe the rare case of a 24-year-old female patient who suffered from early-PTLD (DLBCL: diffuse large B-cell lymphoma) associated with an Epstein-Barr virus (EBV) infection, that developed around the jejunum at 7 months after HTx. She suffered from acute abdominal peritonitis due to perforation of the jejunum soon after the first chemotherapy. She was treated successfully by emergent partial resection of the jejunum and colostomy after the discontinuation of everolimus (EVL) and successive low-dose chemotherapy under careful monitoring and adjustment of intravenous immunosuppressant including cyclosporine (CyA) and prednisolone to avoid a rejection reaction. Prophylactic strategies for early PTLD in HTx recipients should be undertaken with caution. PMID- 26549286 TI - Improvement of Severe Heart Failure after Endovascular Stent Grafting for Thoracic Aortic Aneurysm. AB - Afterload is considered to be an important factor regulating heart failure. Aortic structure or pathology may affect afterload to various extents. However, the contribution of aortic diseases, such as aortic aneurysm or aortic dissection, to heart failure status has not been completely elucidated.Here we describe a 78-year-old patient with severe heart failure who made a dramatic recovery from cardiac decompensation following endovascular thoracic aortic aneurysm surgery. He previously underwent graft replacement for impending rupture of the descending aorta and replacement of both the mitral valve and aortic valve to address valve regurgitation. Subsequently, his left ventricular (LV) function became severely depressed (13%) and serum brain natriuretic peptide (BNP) level remained high (approximately 880-3520 pg/mL). Conversely, his aortic arch was dilated to 70 mm and required surgical intervention. Despite his extremely high vascular surgery risk due to severely depressed cardiac function, stent grafting for thoracic aortic aneurysm was successfully performed. Furthermore, the severity of his depressed cardiac function and heart failure dramatically improved following stent grafting. The left ventricular ejection fraction improved from 13% presurgery to 55% postsurgery and the serum BNP level had significantly decreased to 70- 240 pg/mL. These improvements helped to alleviate the patient's heart failure symptoms, including shortness of breath.This case suggests a possible beneficial effect of aortic aneurysm repair for improving cardiac function and heart failure; our study presents a new concept of another extrinsic factor that can affect cardiac function through modulation of afterload. PMID- 26549287 TI - Ability of 1,5-Anhydro-d-glucitol Values to Predict Coronary Artery Disease in a Non-Diabetic Population. AB - Increasing evidence has indicated that postprandial hyperglycemia affects coronary artery disease (CAD). The serum 1,5-anhydro-d-glucitol (1,5-AG) value is a useful clinical marker to evaluate short-term glycemic status and reflects glycemic excursions with greater sensitivity when compared with hemoglobinA1c (HbA1c), especially for patients in the postprandial state. The aim of this study was to evaluate the predictive value of 1,5-AG for CAD in patients without diabetes mellitus.This study included 729 consecutive patients who had undergone their first coronary angiography. A total of 284 patients (246 diabetic patients and 38 patients with stage 4 or 5 chronic kidney disease) were excluded. The predictive values of 1,5-AG and HbA1c for CAD were evaluated by multivariable logistic regression analysis.Patients with CAD demonstrated significantly lower 1,5-AG values and higher HbA1c values than did patients without CAD (18.6 MUg/mL [12.0, 23.3] versus 19.2 MUg/mL [14.4, 25.2], P = 0.036, and 5.7% [5.5, 5.9] versus 5.6% [5.4, 5.8], P = 0.016, respectively). In multivariable logistic regression analysis, the HbA1c values did not indicate a predictive value for the prevalence of CAD. In contrast, the 1,5-AG levels were still an independent predictor of CAD (adjusted odds ratio 0.96, 95% confidence interval 0.93-0.99, P = 0.0097).Serum 1,5-AG is superior to HbA1c for predicting CAD prevalence in patients without diabetes mellitus. PMID- 26549288 TI - Association of Serum n-3/n-6 Polyunsaturated Fatty Acid Ratio With T-Wave Alternans in Patients With Ischemic Heart Disease. AB - Several studies have demonstrated that oral intake of n-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA), prevents ventricular tachyarrhythmias (VT) with ischemic heart disease, but the underlying mechanisms still remain unclear. Thus, we examined the relation between the serum EPA/arachidonic acid (AA) ratio and electrophysiological properties in patients with ischemic heart disease. The study subjects consisted of 57 patients (46 males, mean age, 66 +/- 13 years) with ischemic heart disease. T-wave alternans (TWA) and heart rate variability were assessed by 24hour Holter ECG, and left ventricular ejection fraction (LVEF) was determined by echocardiography. Fasting blood samples were collected, and the serum EPA/AA ratio was determined. Based on a median value of the serum EPA/AA ratio, all subjects were divided into two groups: serum EPA/AA ratio below 0.33 (Group-L, n = 28) or not (Group-H, n = 29). We compared these parameters between the two groups. LVEF was not different between the two groups. The maximum value of TWA was significantly higher in Group-L than in Group-H (69.5 +/- 22.8 MUV versus 48.7 +/- 12.0 MUV, P = 0.007). In addition, VT defined as above 3 beats was observed in 7 cases (25%) in Group L, but there were no cases of VT in Group-H (P = 0.004). However, low-frequency (LF) component, high-frequency (HF) component, LF to HF ratio, and standard deviation of all R-R intervals were not different between the two groups. These results suggest that a low EPA/AA ratio may induce cardiac electrical instability, but not autonomic nervous imbalance, associated with VT in patients with ischemic heart disease. PMID- 26549289 TI - Giant Thrombus Formation Immediately After Mitral Valvuloplasty. AB - Patients with atrial fibrillation (AF) are at risk of cardioembolism.(1,2)) Atrial thrombus formation associated with AF typically occurs in the left atrial appendage (LAA);(3)) therefore, transesophageal echocardiography (TEE) is important for detection of such a thrombus and measurement of LAA flow velocity.(4,5)) LAA closure is routinely performed during mitral valve surgery in patients with AF to prevent cardiogenic stroke.(6)) We report the case of a 65 year-old woman with severe mitral regurgitation (MR) and AF in whom a giant thrombus formed almost immediately after mitral and tricuspid valvuloplasty and concurrent LAA resection. No atrial thrombus or spontaneous echo contrast (SEC) was detected by TEE before the surgery. However, a giant intramural thrombus was detected in the left atrium 7 days after surgery. It was thought that the atrial dysfunction as well as the change in morphology of the left atrium resulting from the severe MR complicated by AF and congestive heart failure produced a thrombotic substrate. This case suggests that careful surveillance for thrombus formation and careful maintenance of anticoagulation therapy are needed throughout the perioperative period even if no SEC or thrombus is detected before surgery. PMID- 26549290 TI - Addition of a Nitric Oxide Donor to an Angiotensin II Type 1 Receptor Blocker May Cancel Its Blood Pressure-Lowering Effects. AB - While physiological levels of nitric oxide (NO) protect the endothelium and have vasodilatory effects, excessive NO has adverse effects on the cardiovascular system. Recently, new NO-releasing pharmacodynamic hybrids of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) have been developed.We analyzed whether olmesartan with NO-donor side chains (Olm-NO) was superior to olmesartan (Olm) for the control of blood pressure (BP). Although there was no significant difference in binding affinity to AT1 wild-type (WT) receptor between Olm and Olm NO in a cell-based binding assay, the suppressive effect of Olm-NO on Ang II induced inositol phosphate (IP) production was significantly weaker than that of Olm in AT1 WT receptor-expressing cells. While Olm had a strong inverse agonistic effect on IP production, Olm-NO did not. Next, we divided 18 C57BL mice into 3 groups: Ang II (infusion using an osmotic mini-pump) as a control group, Ang II (n = 6) + Olm, and Ang II (n = 6) + Olm-NO groups (n = 6). Olm-NO did not block Ang II-induced high BP after 10 days, whereas Olm significantly decreased BP. In addition, Olm, but not Olm-NO, significantly reduced the ratio of heart weight to body weight (HW/BW) with downregulation of the mRNA levels of atrial natriuretic peptide.An ARB with a NO-donor may cancel BP-lowering effects probably due to excessive NO and a weak blocking effect by Olm-NO toward AT1 receptor activation. PMID- 26549291 TI - Pentoxifylline Prevents Driamycin-Induced Myocardial Fibrosis and Apoptosis in Rats. AB - Adriamycin (ADR) is a potent antineoplastic agent, but long-term treatment is limited by its cumulative, life-threatening cardiomyopathy. Recently, a few reports have shown that pentoxifylline (PTX) might produce cardioprotection in cardiac dysfunction. Here, we investigated the protective effects of PTX on ADR induced cardiomyopathy in rats. Male rats were randomly assigned either to saline, ADR (adriamycin, 5 mg/kg/week), or A (adriamycin, 5 mg/kg/week) + PTX (pentoxifylline, 50 mg/kg/day) groups. After 3 weeks, these animals were sacrificed and the heart tissue was harvested for histological analysis and assessment of hepatocyte growth factor (HGF) and caspase-3 expression. Histopathological findings showed that PTX can alleviate myocardial damage caused by ADR. Cardiac fibrosis was significantly suppressed in the A+PTX group compared to that in the ADR group. The HGF gene expression was decreased significantly in the ADR group compared with the control group, but was increased in the A+PTX group. Caspase-3 was up-regulated in the ADR group, and down-regulated in the A+PTX group. These results show that treatment with PTX exerts a protective effect against ADR-induced myocardial fibrosis via regulation of HGF and caspase 3 gene expression. PTX may thus represent a useful new clinical tool for the treatment of ADR-induced cardiomyopathy. PMID- 26549292 TI - miR-146b-5p promotes invasion and metastasis contributing to chemoresistance in osteosarcoma by targeting zinc and ring finger 3. AB - Osteosarcoma is the most common human primary malignant bone tumor and recurrences are common due to the development of chemoresistance. However, the underlying molecular mechanism for chemoresistance remains unclear. Recent studies demonstrated that miR-146b-5p, an important regulator in tumorigenesis, was involved in chemoresistance in thyroid cancer, lymphoma. Thus, to confirm the role of miR-146b-5p in osteosarcoma, the study was divided into three steps: first, miR-146b-5p in paired samples were assessed using a quantitative real-time PCR (qRT-PCR) assay from osteosarcoma patients. Second, to confirm the role of miR-146b-5p, we applied lentivirus system to overexpression and knockdown of miR 146b-5p, respectively, in MG-63 osteosarcoma cell line. Third, luciferase assays were performed to determine whether Wnt/beta-catenin pathway participated in the role of miR-146b-5p on chemoresistance. As a result, miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1 endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness. It also increased resistance to chemotherapy through the regulation of ZNRF3, and suggested novel potential therapeutic targets for the treatment of osteosarcoma. PMID- 26549293 TI - Forager bees (Apis mellifera) highly express immune and detoxification genes in tissues associated with nectar processing. AB - Pollinators, including honey bees, routinely encounter potentially harmful microorganisms and phytochemicals during foraging. However, the mechanisms by which honey bees manage these potential threats are poorly understood. In this study, we examine the expression of antimicrobial, immune and detoxification genes in Apis mellifera and compare between forager and nurse bees using tissue specific RNA-seq and qPCR. Our analysis revealed extensive tissue-specific expression of antimicrobial, immune signaling, and detoxification genes. Variation in gene expression between worker stages was pronounced in the mandibular and hypopharyngeal gland (HPG), where foragers were enriched in transcripts that encode antimicrobial peptides (AMPs) and immune response. Additionally, forager HPGs and mandibular glands were enriched in transcripts encoding detoxification enzymes, including some associated with xenobiotic metabolism. Using qPCR on an independent dataset, we verified differential expression of three AMP and three P450 genes between foragers and nurses. High expression of AMP genes in nectar-processing tissues suggests that these peptides may contribute to antimicrobial properties of honey or to honey bee defense against environmentally-acquired microorganisms. Together, these results suggest that worker role and tissue-specific expression of AMPs, and immune and detoxification enzymes may contribute to defense against microorganisms and xenobiotic compounds acquired while foraging. PMID- 26549294 TI - Ibrutinib: another weapon in our arsenal against lympho-proliferative disorders. AB - In Volume 16, issue 12 of Expert Opinion on Pharmacotherapy, an important article on the new drug ibrutinib was published. This new drug promises to further improve outcome in the treatment of several lympho-proliferative disorders. In this editorial, the most important findings of the article looking particularly to the integration of ibrutinib in current clinical practice will be summarized. Finally this editorial will focus on the next challenges for scientists and physicians in the treatment of lympho-proliferative disorders. PMID- 26549296 TI - Secondary production of the fiddler crab Uca rapax from mangrove areas under anthropogenic eutrophication in the Western Atlantic, Brazil. AB - Fiddler crabs Uca rapax were analyzed in three mangrove areas located in both a lagoon and estuarine system in order to study the influence of eutrophication on their population dynamics and production. Populations at the three sites showed a biased sex ratio. Densities were similar at the three sites, but biomass was higher at the lagoon system. Despite biomass being higher at the most eutrophic site, this site exhibited the lowest production. Regarding age structure, the population inhabiting the less eutrophic site mainly comprised younger crabs. The lower production and smaller P/B ratio found in the more eutrophic site were most likely consequences of a high mortality rate and an aged population. Our study evidences the high plasticity of the fiddler crab U. rapax, and confirms secondary production and P/B ratio estimates as useful tools to assess the effects of environmental change. PMID- 26549295 TI - Introduction to the Special Issue on the Studies on the Implementation of Integrated Models of Alcohol, Tobacco, and/or Drug Use Interventions and Medical Care. AB - National efforts are underway to integrate medical care and behavioral health treatment. This special issue of the Journal of Substance Abuse Treatment presents 13 papers that examine the integration of substance use interventions and medical care. In this introduction, the guest editors first describe the need to examine the integration of substance use treatment into medical care settings. Next, an overview of the emerging field of implementation science and its applicability to substance use intervention integration is presented. Preview summaries of each of the articles included in this special issue are given. Articles include empirical studies of various integration models, study protocol papers that describe currently funded implementation research, and one review/commentary piece that discusses federal research priorities, integration support activities and remaining research gaps. These articles provide important information about how to guide future health system integration efforts to treat the millions of medical patients with substance use problems. PMID- 26549297 TI - Neutral red cytotoxicity assays for assessing in vivo carbon nanotube ecotoxicity in mussels--Comparing microscope and microplate methods. AB - The purpose of the present study was to compare two neutral red retention methods, the more established but very labour-intensive microscope method (NRR) against the more recently developed microplate method (NRU). The intention was to explore whether the sample volume throughput could be increased and potential operator bias avoided. Mussels Mytilus sp. were exposed in vivo to 50, 250 and 500 MUg L(-1) single (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Using the NRR method, SWCNTs and MWCNTs caused concentration dependent decreases in neutral red retention time. However, a concentration dependent decrease in optical density was not observed using the NRU method. We conclude that the NRU method is not sensitive enough to assess carbon nanotube ecotoxicity in vivo in environmentally relevant media, and recommend using the NRR method. PMID- 26549298 TI - The role of the COMT val158met polymorphism in mediating aversive learning in visual cortex. AB - The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (SNP) alters metabolic activity of the COMT enzyme regulating catecholamines, with the Val (valine) allele resulting in 40% greater enzymatic activity than the Met (methionine) allele. Previous research has identified systematic inter individual differences in cognitive and behavioral phenotypes related to this polymorphism, often attributed to the fact that extracellular dopamine in the prefrontal cortex is strongly affected by the COMT enzyme. The neurophysiological mechanisms mediating these inter-individual differences in specific brain systems and task contexts remain to be established however. In the current study, we examined the extent to which physio-mechanistic differences by COMT genotype affect somato-visceral and visual cortical responses to learned threat cues. Classical aversive differential conditioning was implemented using rapidly phase reversing grating stimuli, previously shown to engage retinotopic visual cortex. Differential response patterns in sensory and autonomic systems were elicited by pairing one grating (CS+, conditioned stimulus), but not the other (CS-), with a noxious stimulus. Dense-array electroencephalography and somato-visceral measures of defensive reactivity were recorded in addition to self-report data. Individuals of the Val/Val genotype, compared to Met allele carriers, reliably showed greater initial enhancement in their visuocortical response to the CS+, accompanied by stronger defensive engagement, indexed by heart rate acceleration and startle potentiation. The finding that COMT polymorphism status affects threat cue reactivity at the visuocortical level is consistent with the notion that sensory processing of threat is facilitated by strong re-entrant bias signals from anterior areas, including the prefrontal cortex. PMID- 26549300 TI - Realistic simulation of artefacts in diffusion MRI for validating post-processing correction techniques. AB - In this paper we demonstrate a simulation framework that enables the direct and quantitative comparison of post-processing methods for diffusion weighted magnetic resonance (DW-MR) images. DW-MR datasets are employed in a range of techniques that enable estimates of local microstructure and global connectivity in the brain. These techniques require full alignment of images across the dataset, but this is rarely the case. Artefacts such as eddy-current (EC) distortion and motion lead to misalignment between images, which compromise the quality of the microstructural measures obtained from them. Numerous methods and software packages exist to correct these artefacts, some of which have become de facto standards, but none have been subject to rigorous validation. In the literature, improved alignment is assessed using either qualitative visual measures or quantitative surrogate metrics. Here we introduce a simulation framework that allows for the direct, quantitative assessment of techniques, enabling objective comparisons of existing and future methods. DW-MR datasets are generated using a process that is based on the physics of MRI acquisition, which allows for the salient features of the images and their artefacts to be reproduced. We apply this framework in three ways. Firstly we assess the most commonly used method for artefact correction, FSL's eddy_correct, and compare it to a recently proposed alternative, eddy. We demonstrate quantitatively that using eddy_correct leads to significant errors in the corrected data, whilst eddy is able to provide much improved correction. Secondly we investigate the datasets required to achieve good correction with eddy, by looking at the minimum number of directions required and comparing the recommended full-sphere acquisitions to equivalent half-sphere protocols. Finally, we investigate the impact of correction quality by examining the fits from microstructure models to real and simulated data. PMID- 26549299 TI - Effect of trial-to-trial variability on optimal event-related fMRI design: Implications for Beta-series correlation and multi-voxel pattern analysis. AB - Functional magnetic resonance imaging (fMRI) studies typically employ rapid, event-related designs for behavioral reasons and for reasons associated with statistical efficiency. Efficiency is calculated from the precision of the parameters (Betas) estimated from a General Linear Model (GLM) in which trial onsets are convolved with a Hemodynamic Response Function (HRF). However, previous calculations of efficiency have ignored likely variability in the neural response from trial to trial, for example due to attentional fluctuations, or different stimuli across trials. Here we compare three GLMs in their efficiency for estimating average and individual Betas across trials as a function of trial variability, scan noise and Stimulus Onset Asynchrony (SOA): "Least Squares All" (LSA), "Least Squares Separate" (LSS) and "Least Squares Unitary" (LSU). Estimation of responses to individual trials in particular is important for both functional connectivity using "Beta-series correlation" and "multi-voxel pattern analysis" (MVPA). Our simulations show that the ratio of trial-to-trial variability to scan noise impacts both the optimal SOA and optimal GLM, especially for short SOAs<5s: LSA is better when this ratio is high, whereas LSS and LSU are better when the ratio is low. For MVPA, the consistency across voxels of trial variability and of scan noise is also critical. These findings not only have important implications for design of experiments using Beta-series regression and MVPA, but also statistical parametric mapping studies that seek only efficient estimation of the mean response across trials. PMID- 26549301 TI - Baseline oxygenation in the brain: Correlation between respiratory-calibration and susceptibility methods. AB - New MRI methods for noninvasive imaging of baseline oxygen extraction fraction (OEF) in the brain show great promise. Quantitative O2 imaging (QUO2) applies a biophysical model to measure OEF in tissue from BOLD, cerebral blood flow (CBF), and end-tidal O2 (ETO2) signals acquired during two or more gas manipulations. Alternatively, quantitative susceptibility mapping (QSM) maps baseline OEF along cerebral vessels based on the deoxyhemoblogin (dHb) susceptibility shift between veins and water. However, these approaches have not been carefully compared to each other or to known physiological signals. The aims of this study were to compare OEF values by QUO2 and QSM; and to see if baseline OEF relates to BOLD and CBF changes during a visual task. Simultaneous BOLD and arterial spin labeling (ASL) scans were acquired at 7T in 11 healthy subjects continuously during hypercapnia (5% CO2, 21% O2), hyperoxia (100% O2), and carbogen (5% CO2, 95% O2) for QUO2 analysis. Separate BOLD-ASL scans were acquired during a checkerboard stimulus to identify functional changes in the visual cortex. Gradient echo phase images were also collected at rest for QSM reconstruction of OEF along cerebral veins draining the visual cortex. Mean baseline OEF was (43.5+/-14)% for QUO2 with two gases, (42.3+/-17)% for QUO2 with three gases, and (29.4+/-3)% for QSM across volunteers. Three-gas QUO2 values of OEF correlated with QSM values of OEF (P=0.03). However, Bland-Altman analysis revealed that QUO2 tended to measure higher baseline OEF with respect to QSM, which likely results from underestimation of the hyperoxic BOLD signal and low signal-to-noise ratio of the ASL acquisitions. Across subjects, the percent CBF change during the visual task correlated with OEF measured by 3-gas QUO2 (P<0.04); and by QSM (P=0.035), providing evidence that the new methods measure true variations in brain physiology across subjects. PMID- 26549302 TI - Item response theory analysis of Working Alliance Inventory, revised response format, and new Brief Alliance Inventory. AB - OBJECTIVE: The Working Alliance Inventory (WAI) has made great contributions to psychotherapy research. However, studies suggest the 7-point response format and 3-factor structure of the client version may have psychometric problems. This study used Rasch item response theory (IRT) to (a) improve WAI response format, (b) compare two brief 12-item versions (WAI-sr; WAI-s), and (c) develop a new 16 item Brief Alliance Inventory (BAI). METHOD: Archival data from 1786 counseling center and community clients were analyzed. RESULTS: IRT findings suggested problems with crossed category thresholds. A rescoring scheme that combines neighboring responses to create 5- and 4-point scales sharply reduced these problems. Although subscale variance was reduced by 11-26%, rescoring yielded improved reliability and generally higher correlations with therapy process (session depth and smoothness) and outcome measures (residual gain symptom improvement). The 16-item BAI was designed to maximize "bandwidth" of item difficulty and preserve a broader range of WAI sensitivity than WAI-s or WAI-sr. CONCLUSIONS: Comparisons suggest the BAI performed better in several respects than the WAI-s or WAI-sr and equivalent to the full WAI on several performance indicators. PMID- 26549303 TI - In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation. AB - Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549304 TI - Predictive value of psychosocial assessment for the mortality of patients waiting for liver transplantation. AB - Selecting suitable candidates for liver transplantation is the most challenging task of pre-transplant evaluation. In addition to somatic assessment, psychosocial evaluation has been proven important in identifying patients at high risk of potential failure. The Transplant Evaluation Rating Scale (TERS) is a widely used rating instrument for the assessment of psychosocial risk factors before liver transplantation. The aim of this study was to explore the predictive value of TERS for mortality in liver transplant patients before and after transplantation. The medical records of patients referred for psychiatric evaluation before liver transplantation between 2003 -2013 were analysed. Administering TERS was part of the pre-transplant evaluation. The TERS scores of patients who died before and after transplantation were compared with those who survived following transplantation. One hundred and sixteen patients were referred for pre-transplant psychiatric evaluation. Patients with successful liver transplants scored significantly lower on TERS than those who died before transplantation (30.65 +/- 6.06 vs. 34.75 +/- 8.25, p = .031). Patients who died after transplantation scored significantly better on TERS than those who died before transplantation (28.79 +/- 2.81 vs. 34.75 +/- 8.25, p = .003). There was no significant difference between the deceased and surviving transplanted patients' TERS scores (28.79 +/- 2.81 vs. 31.19 +/- 6.66, p = .365). TERS appears to be a suitable rating instrument to help select candidates who have higher chance to survive prior to transplantation but it could not predict post transplant mortality. PMID- 26549305 TI - Cost-effectiveness of edoxaban for the treatment of venous thromboembolism based on the Hokusai-VTE study. AB - OBJECTIVE: Venous thromboembolism (VTE) is associated with almost 300,000 deaths per year in the United States. Novel oral anticoagulants (NOACs) offer an alternative to warfarin-based therapy without monitoring requirements and with fewer drug and food interactions. Edoxaban, a direct Xa inhibitor, is approved by the Food and Drug Administration (FDA), based upon results of the Hokusai-VTE Phase 3 trial. The trial demonstrated that edoxaban administered once daily after initial treatment with heparin was non-inferior in reducing the risk of VTE recurrence and caused significantly less major and clinically relevant non-major (CRNM) bleeding compared to warfarin. The objective of this study was to evaluate the cost-effectiveness of edoxaban versus warfarin for the treatment of adults with VTE. METHODS: A cost-effectiveness model was developed using patient-level data from the Hokusai-VTE trial, clinical event costs from real-world databases, and drug acquisition costs for warfarin of $0.36 and edoxaban of $9.24 per tablet. RESULTS: From a U.S. health-care delivery system perspective, the incremental cost-effectiveness ratio (ICER) was $22,057 per quality adjusted life year (QALY) gained. Probabilistic sensitivity analysis showed that edoxaban had an ICER <$50,000 per QALY gained relative to warfarin in 67% of model simulations. The result was robust to variation in key model parameters including the cost and disutility of warfarin monitoring. CONCLUSION: Despite its higher drug acquisition cost, edoxaban is a cost-effective alternative to warfarin for the treatment of VTE. PMID- 26549307 TI - Occurrence and distribution of Malassezia species on skin and external ear canal of horses. AB - The aim of this study was to investigate the prevalence of Malassezia species from the body skin and external ear canal of healthy horses. The samples were obtained by scraping the skin surface from the nose, groin and dorsum and swabbing from the external ear canal of 163 animals, and then incubated on sabouraud dextrose agar and modified Dixon agar. Malassezia species were isolated from 34.9% of horses. The percentages of Malassezia species were 64.3% for Arab, 35.7% for Persian, 35.4% for Thoroughbred and 27.1% for Turkmen breeds. The greatest abundance of Malassezia species was found in the external ear canal (47.7%, representing significant difference with other sites), followed by nose (26.3%), groin (15.8%) and dorsum (10.5%) (P < 0.05). A total of 57 strains from six Malassezia species were detected with a frequency rate as follows: M. pachydermatis (33.3%), M. globosa (26.3%), M. sympodialis (14.1%), M. restricta (10.5%), M. obtusa (8.8%) and M. furfur (7%). The most common age-group affected was 1-3 years (59.4%). This study confirmed that cutaneous Malassezia microbiota in healthy horses varies by body site and age but not by breed and gender, representing M. pachydermatis as the most prevalent species on horse skin. PMID- 26549306 TI - Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly. AB - Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH secreting tumors. PMID- 26549308 TI - Structural modeling of the ExuR and UxuR transcription factors of E. coli: search for the ligands affecting their regulatory properties. AB - Gammaproteobacteria get energy for their growth from different carbon sources using either glycolysis or alternative metabolic pathways induced in stress conditions. These metabolic switches are coordinated by complex interplay of regulatory proteins sensing concentrations of available metabolites by mechanisms yet to be understood. Here, we use two transcriptional regulators, ExuR and UxuR, controlling d-galacturonate (d-gal) and d-glucuronate metabolism in Escherichia coli, as the targets for computational search of low-molecular compounds capable to bind their ligand-binding domains. Using a flexible molecular docking, we modeled the interactions of these proteins with substrates and intermediates of glycolysis, Ashwell and Entner-Doudoroff pathways. For UxuR, the two preferred sites of ligand binding were found: one is located within the C-terminal domain, while another occupies the interdomain space. For ExuR, the only one preferred site was detected in the interdomain area. Availability of this area to different ligands suggests that, similar to the Lac repressor, the DNA-binding properties of UxuR and ExuR may be changed by repositioning of their domains. Experimental assays confirmed the ability of ligands with highest affinities to bind the regulatory proteins and affect their interaction with DNA. d-gal that is carried into the cell by the ExuT transporter appeared to be the best ligand for repressor of the exuT transcription, ExuR. For UxuR, the highest affinity was found for d-fructuronate transported by GntP, which biosynthesis is repressed by UxuR. Providing a feedback loop to balance the concentrations of different nutrients, such ligand-mediated modulation can also coordinate switching between different metabolic pathways in bacteria. PMID- 26549309 TI - Robot-assisted resection of gastrointestinal stromal tumors (GIST): a single center case series and literature review. AB - BACKGROUND: Robotic techniques are claimed to be an alternative to laparoscopic and open approaches for gastrointestinal stromal tumors (GIST) treatment. Our aim is to present our single center experience and a literature review. MATERIALS AND METHODS: From June 2012 to August 2014, six patients with preoperative diagnosis of GIST were treated by robotic surgery at Sanchinarro University Hospital. RESULTS: Two GIST tumors were localized in the second part of the duodenum, one in the first portion, two in the gastricantrum and another in the angular notch. Surgical procedures performed were two subtotal gastrectomies, one gastric wedge resection and three duodenal enucleations. None of the interventions needed conversion to open surgery. Mean operative time was 245 min (150-540). Mean hospital stay was 10.5 days (6-24). All lesions had microscopically negative resection margins. Mean follow-up was 24 months (8-33) with a disease-free survival rate of 100%. CONCLUSIONS: A robotic approach for GIST tumors is a safe and feasible procedure with a well-accepted oncological surgical result. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549310 TI - Reciprocal regulation of RORgammat acetylation and function by p300 and HDAC1. AB - T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORgammat) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORgammat itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORgammat at its K81 residue. Knockdown of p300 downregulates RORgammat protein and RORgammat mediated gene expression in Th17 cells. In addition, p300 can promote RORgammat mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORgammat and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORgammat, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORgammat-mediated transcriptional activation of IL-17. PMID- 26549311 TI - Impact of negative media publicity on attention-deficit/hyperactivity disorder medication in Taiwan. AB - PURPOSE: This study explores trends in attention-deficit/hyperactivity disorder (ADHD) medications in Taiwan from 2000 to 2011 and whether negative media coverage of Ritalin in January 2010 impacted ADHD prescriptions throughout the country. METHOD: Patients throughout Taiwan who had been newly diagnosed with ADHD (n = 145,269) between January 2000 and December 2011 were selected from Taiwan's National Health Insurance database as subjects for this study. We analyzed monthly and yearly data on person-days of treatment with immediate release methylphenidate (IR-MPH), osmotic controlled-release formulation of methylphenidate (OROS-MPH), and atomoxetine (ATX) using linear models of curve estimation and the time series expert modeler. RESULTS: Of our sample, 57.8%, 28.9%, and 4.3% had been prescribed one or more doses of IR-MPH, OROS-MPH, or ATX, respectively. The annual person-days of IR-MPH use increased regularly from 2000 to 2009, dropped abruptly in 2010, and then increased again the next year. Furthermore, the person-days of OROS-MPH prescriptions did not reach their expected goal in 2010; however, the person-days of ATX prescriptions have increased constantly since entering the market in 2007. Compared with patients newly diagnosed with ADHD in 2009, those newly diagnosed in 2010 were less likely to be treated with medication. CONCLUSION: These findings suggest that negative publicity affected the writing of stimulant prescriptions for ADHD patients throughout Taiwan. Media reporting has a vital role in influencing children with ADHD, their parents, and their willingness to accept pharmacotherapy as treatment. PMID- 26549313 TI - Aspects of nursing student placements associated with perceived likelihood of working in residential aged care. AB - AIMS AND OBJECTIVES: To investigate which aspects of student nurses' experiences of residential aged care facility clinical placements affect perceived likelihood of choosing a career in residential aged care post graduation. BACKGROUND: Poor clinical placement experiences as a student contribute to nurses' reluctance to work in aged care. Various factors have been found to improve the placement experience and influence students' attitudes and employment intentions. Missing from the literature is a quantitative - rather than qualitative - exploration of which attributes of an aged care placement link to perceived likelihood of working in residential aged care post graduation. DESIGN: Supported residential aged care placement programmes were developed for nursing students using an evidence-based best-practice model within an action research framework. Staff formed a mentor group in two facilities. During placement, weekly feedback meetings were held for students and mentors. METHODS: Second-year nursing students (n = 71) participating in a three- or four-week placement programme at two Tasmanian residential aged care facilities (September 2011-May 2013) completed questionnaires on placement experiences. Measures of association (correlation coefficients) were used to assess the effect of a range of variables on the likelihood of working in an aged care facility post graduation. RESULTS: Associations were identified between the likelihood of working in residential aged care post graduation and nurse mentor-student feedback exchange, Teaching and Learning Score and supportiveness of care workers. CONCLUSIONS: This study adds to the literature by providing quantitative evidence that certain aspects of aged care placements influence attitudes to working in these sites post graduation. RELEVANCE TO CLINICAL PRACTICE: To increase interest in working in residential aged care, the teaching and learning environment needs improvement, opportunities should be proffered for mentor-student feedback exchange during placements and care workers need support to mentor effectively. PMID- 26549312 TI - The comparative risk of developing postoperative complications in patients with distal radius fractures following different treatment modalities. AB - In this study, we performed a network meta-analysis to compare the outcomes of seven most common surgical procedures to fix DRF, including bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. Published studies were retrieved through PubMed, Embase and Cochrane Library databases. The database search terms used were the following keywords and MeSH terms: DRF, bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. The network meta-analysis was performed to rank the probabilities of postoperative complication risks for the seven surgical modalities in DRF patients. This network meta-analysis included data obtained from a total of 19 RCTs. Our results revealed that compared to DRF patients treated with bridging external fixation, marked differences in pin-track infection (PTI) rate were found in patients treated with plaster fixation, volar plating, and dorsal and volar plating. Cluster analysis showed that plaster fixation is associated with the lowest probability of postoperative complication in DRF patients. Plaster fixation is associated with the lowest risk for postoperative complications in DRF patients, when compared to six other common DRF surgical methods examined. PMID- 26549314 TI - Nutrient loading alters the performance of key nutrient exchange mutualisms. AB - Nutrient exchange mutualisms between phototrophs and heterotrophs, such as plants and mycorrhizal fungi or symbiotic algae and corals, underpin the functioning of many ecosystems. These relationships structure communities, promote biodiversity and help maintain food security. Nutrient loading may destabilise these mutualisms by altering the costs and benefits each partner incurs from interacting. Using meta-analyses, we show a near ubiquitous decoupling in mutualism performance across terrestrial and marine environments in which phototrophs benefit from enrichment at the expense of their heterotrophic partners. Importantly, heterotroph identity, their dependence on phototroph derived C and the type of nutrient enrichment (e.g. nitrogen vs. phosphorus) mediated the responses of different mutualisms to enrichment. Nutrient-driven changes in mutualism performance may alter community organisation and ecosystem processes and increase costs of food production. Consequently, the decoupling of nutrient exchange mutualisms via alterations of the world's nitrogen and phosphorus cycles may represent an emerging threat of global change. PMID- 26549315 TI - Effects of team-building on communication and teamwork among nursing students. AB - AIM: The aim of this study was to assess the effects of team-building on communication and teamwork (i.e. teamwork skills and team effectiveness) among nursing students. BACKGROUND: Team-building is effective for improving communication and teamwork among the nursing organization. However, the effects of team-building are not well known especially in Korea. METHODS: This study used a quasi-experimental design. The sample was composed of 195 junior-year nursing students in Korea. The experimental group (100 subjects) participated in team building activities over a 100-day period, whereas no intervention was applied to the control group (95 subjects). Pretest was conducted in both groups, and post test was conducted after the 100-day intervention. FINDINGS: The pre-post change in mean communication competence score did not differ between the two groups. However, the mean scores for teamwork skills and team effectiveness differed significantly between the two groups after team-building activity. LIMITATIONS: This study was not a double-blind test, and randomized sampling was not implemented. Caution should thus be used when interpreting the findings. CONCLUSION: Team-building activities were effective for improving the teamwork skills and team effectiveness among Korean nursing students. IMPLICATIONS FOR NURSING EDUCATION: It is recommended that team-building activities should be included regularly as an integral educational approach in nursing education. The findings suggest that suggests that team-building for improving communication and teamwork should be designated as one of the required criteria for nursing college programme accreditation in many countries, including Korea. However team-building requires further testing to verify this across cultures. IMPLICATIONS FOR NURSING POLICY: Nurses need to receive formal team-building training for improving communication and teamwork, and formal education should be included in their job training schedule. It is recommended that communication competence and teamwork be used as one of job performance evaluations in their workplace. PMID- 26549316 TI - Acute and chronic ecotoxicity of carbaryl with a battery of aquatic bioassays. AB - The ecotoxic effects of carbaryl (carbamate insecticide) were investigated with a battery of four aquatic bioassays. The nominal effective concentrations immobilizing 50% of Daphnia magna (EC50) after 24 and 48 h were 12.76 and 7.47 ug L(-1), respectively. After 21 days of exposure of D. magna, LOECs (lowest observed effect concentrations) for cumulative molts and the number of neonates per surviving adult were observed at carbaryl concentration of 0.4 ug L(-1). An increase of embryo deformities (curved or unextended shell spines) was observed at 1.8 and 3.7 ug L(-1), revealing that carbaryl could act as an endocrine disruptor in D. magna. Other bioassays of the tested battery were less sensitive: the IC50-72h and IC10-72h of the algae Pseudokirchneriella subcapitata were 5.96 and 2.87 mg L(-1), respectively. The LC50-6d of the ostracod Heterocypris incongruens was 4.84 mg L(-1). A growth inhibition of H. incongruens was registered after carbaryl exposure and the IC20-6d was 1.29 mg L(-1). Our results suggest that the daphnid test sensitivity was better than other used tests. Moreover, carbaryl has harmful and toxic effects on tested species because it acts at low concentrations on diverse life history traits of species and induce embryo deformities in crustaceans. PMID- 26549317 TI - Me2Zn-Mediated Catalytic Enantio- and Diastereoselective Addition of TosMIC to Ketones. AB - The first catalytic asymmetric addition of TosMIC to unactivated ketones is presented. A combination of Me2Zn and aminoalcohol catalyst promoted the aldol addition/cyclization reaction to render oxazolines possessing a fully substituted stereocenter with excellent yields (up to 92%), high enantioselectivities (up to 96%), and complete diastereoselectivity. The chiral oxazolines were then used to give, after a straightforward acid hydrolysis, enantioenriched building blocks bearing tertiary alcohol motifs such as hydroxylaldehydes, hydroxylacids, and hydroxylesters without racemization. PMID- 26549318 TI - Flexible navigation response in common cuckoos Cuculus canorus displaced experimentally during migration. AB - Migrating birds follow innate species-specific migration programs capable of guiding them along complex spatio-temporal routes, which may include several separate staging areas. Indeed, migration routes of common cuckoos Cuculus canorus show little variation between individuals; yet, satellite tracks of 11 experimentally displaced adults revealed an unexpected flexibility in individual navigation responses. The birds compensated for the translocation to unfamiliar areas by travelling toward population-specific staging areas, demonstrating true navigation capabilities. Individual responses varied from travelling toward the first stopover in northern Europe to flying toward the Central-African winter grounds, the latter including several stopovers in unfamiliar areas. Apparently, the cuckoos possess spatial knowledge far beyond their population-specific flyway scale, and make individual decisions likely based on an assessment of perceived gain and cost of alternative route options. PMID- 26549319 TI - Aqueous size-exclusion chromatographic separations of intact proteins under native conditions: Effect of pressure on selectivity and efficiency. AB - The selectivity and separation efficiency of aqueous size-exclusion chromatographic separations of intact proteins were assessed for different flow rates, using columns packed with 3 and 5 MUm silica particles containing 150 and 290 A stagnant pores. A mixture of intact proteins with molecular weights ranging between 17 000 and 670 000 Da was used to construct the calibration curves. Both the model fit and the predictive properties, using a leave-one-out strategy, of different polynomial models (up to fifth order) were evaluated for different flow rates. The best compromise between model fit and predictive properties was obtained using a third-order polynomial model. The accuracy of the predictive properties decreased with 10% with an eightfold increase in the flow rate. No changes in retention factors (hence selectivity) were observed in the flow-rate range applied. A strong correlation between molecular weight and plate height was observed. Exclusion of large-molecular-weight proteins led to a significant reduction in the stationary-phase mass-transfer contribution to the total plate height value, and this effect was also independent of the flow rate applied. The kinetic-performance limits, in terms of plate number and time, and optimal column length particle-size combinations were determined at the maximum recommended operating pressure of the size-exclusion chromatography columns (20 MPa). Finally, the possibilities of method speed-up using ultra-high-pressure size exclusion chromatography in combination with columns packed with sub-2 MUm particles are discussed. PMID- 26549320 TI - MicroRNA-10b suppresses the migration and invasion of chondrosarcoma cells by targeting brain-derived neurotrophic factor. AB - MicroRNAs (miRs) can lead to mRNA degradation or inhibit protein translation through directly binding to the 3'-untranslational region (UTR) of their target mRNAs. Deregulation of miR-10b has been reported to be associated with chondrosarcoma. However, the role of miR-10b in chondrosarcoma cell migration and invasion, as well as the underlying mechanisms, has not been investigated. In the present study, it was demonstrated that miR-10b was notably downregulated in the JJ012 and SW1353 chondrosarcoma cell lines compared with the TC28a2 normal chondrocyte line. Treatment with DNA demethylating agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor 4-phenylbutyric acid, or transfection with miR 10b mimics promoted the expression of miR-10b, which further suppressed the migratory and invasive capacities of JJ012 chondrosarcoma cells. Moreover, brain derived neurotrophic factor (BDNF) was identified as a novel target of miR-10b, and its protein expression level was negatively regulated by miR-10b in JJ012 cells. Furthermore, overexpression of BDNF reversed the inhibitory effect of miR 10b upregulation on the migration and invasion of JJ012 cells. In addition, the data suggest that matrix metalloproteinase 1 (MMP1) may be involved in the miR 10b/BDNF-mediated chondrosarcoma cell migration and invasion in JJ012 cells. In conclusion, these findings suggest that miR-10b/BDNF may serve as a potential therapeutic target for chondrosarcoma. PMID- 26549321 TI - A Review of Sodium Glucose Co-transporter 2 Inhibitors Canagliflozin, Dapagliflozin and Empagliflozin. AB - Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of anti diabetic medications. Canagliflozin was the first drug approved in this group in 2013 and subsequently dapagliflozin was approved in January 2014 and empagliflozin was approved in August 2014. Preclinical studies have demonstrated safety, tolerability, and efficacy in terms of glycemic control and HbA1c level in type 2 diabetes mellitus (T2DM) patients in comparison to other anti-diabetic drugs. The U.S. Food and Drug Administration (FDA) recently released a warning that some of the patients who used SGLT2 inhibitors developed diabetic ketoacidosis (DKA). Empagliflozin has showed safety in type 2 diabetics with renal impairment. Each of these medications can be used as a single treatment or in combination with other anti-diabetic medications. PMID- 26549322 TI - Precursor-route ZnO films from a mixed casting solvent for high performance aqueous electrolyte-gated transistors. AB - We significantly improved the performance of precursor-route semiconducting zinc oxide (ZnO) films in electrolyte-gated thin film transistors (TFTs). We find that the organic precursor to ZnO, zinc acetate (ZnAc), dissolves more readily in a 1 : 1 mixture of ethanol (EtOH) and acetone than in pure EtOH, pure acetone, or pure isopropanol. XPS and SEM characterisation show improved morphology of ZnO films converted from a mixed solvent cast ZnAc precursor compared to the EtOH cast precursor. When gated with a biocompatible electrolyte, phosphate buffered saline (PBS), ZnO thin film transistors (TFTs) derived from mixed solvent cast ZnAc give 4 times larger field effect current than similar films derived from ZnAc cast from pure EtOH. The sheet resistance at VG = VD = 1 V is 30 kOmega ?( 1), lower than for any organic TFT, and lower than for any electrolyte-gated ZnO TFT reported to date. PMID- 26549323 TI - Proximity Effect Induced Electronic Properties of Graphene on Bi2Te2Se. AB - We report that the pi-electrons of graphene can be spin-polarized to create a phase with a significant spin-orbit gap at the Dirac point (DP) using a graphene interfaced topological insulator hybrid material. We have grown epitaxial Bi2Te2Se (BTS) films on a chemical vapor deposition (CVD) graphene. We observe two linear surface bands from both the CVD graphene notably flattened and BTS coexisting with their DPs separated by 0.53 eV in the photoemission data measured with synchrotron photons. We further demonstrate that the separation between the two DPs, Delta(D-D), can be artificially fine-tuned by adjusting the amount of Cs atoms adsorbed on the graphene to a value as small as Delta(D-D) = 0.12 eV to find any proximity effect induced by the DPs. Our density functional theory calculation shows the opening of a spin-orbit gap of ~20 meV in the pi-band, enhanced by 3 orders of magnitude from that of a pristine graphene, and a concomitant phase transition from a semimetallic to a quantum spin Hall phase when Delta(D-D) <= 0.20 eV. We thus present a practical means of spin-polarizing the pi-band of graphene, which can be pivotal to advance graphene-based spintronics. PMID- 26549325 TI - Counterintuitive issues in the charge transport through molecular junctions. AB - Whether at phenomenological or microscopic levels, most theoretical approaches to charge transport through molecular junctions postulate or attempt to justify microscopically the existence of a dominant molecular orbital (MO). Within such single level descriptions, experimental current-voltage I-V curves are sometimes/often analyzed by using analytical formulas expressing the current as a cubic expansion in terms of the applied voltage V, and the possible V-driven shifts of the level energy offset relative to the metallic Fermi energy epsilon0 are related to the asymmetry of molecule-electrode couplings or an asymmetric location of the "center of gravity" of the MO with respect to electrodes. In this paper, we present results demonstrating the failure of these intuitive expectations. For example, we show how typical data processing based on cubic expansions yields a value of epsilon0 underestimated by a typical factor of about two. When compared to theoretical results of DFT approaches, which typically underestimate the HOMO-LUMO gap by a similar factor, this may create the false impression of "agreement" with experiments in situations where this is actually not the case. Furthermore, such cubic expansions yield model parameter values dependent on the bias range width employed for fitting, which is unacceptable physically. Finally, we present an example demonstrating that, counter intuitively, the bias-induced change in the energy of an MO located much closer to an electrode can occur in a direction that is opposite to the change in the Fermi energy of that electrode. This is contrary to what one expects based on a "lever rule" argument, according to which the MO "feels" the local value of the electric potential, which is assumed to vary linearly across the junction and is closer to the potential of the closer electrode. This example emphasizes the fact that screening effects in molecular junctions can have a subtle character, contradicting common intuition. PMID- 26549324 TI - Noradrenergic inputs from locus coeruleus to posterior ventral tegmental area are essential to support ethanol reinforcement. AB - Although dysregulation of the dopaminergic mesolimbic system is generally considered central to addiction, the involvement of other circuits is increasingly being appreciated. An interaction between locus coeruleus (LC) noradrenergic neurons and the posterior ventral tegmental area (pVTA) dopaminergic system, in the processing of drug-triggered reward, has been suggested, but not demonstrated in behaving animals. Herein, we try to tease out the precise role of noradrenergic neurons in the LC-VTA circuit in mediating reward and reinforcement behavior associated with ethanol. In the standard two lever (active/inactive) operant paradigm, the rats were trained to self administer ethanol in pVTA and subjected to pharmacological intervention. Intra pVTA administration of phenylephrine (alpha-1 adrenoceptor agonist) increased ethanol self-administration, while prazosin and disulfiram (agents that reduce noradrenergic tone) produced opposite effects. While degeneration [N-(2 chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, DSP-4, intraperitoneal route] or silencing (lidocaine or muscimol, both via intra-LC route) of the LC noradrenergic neurons decreased, phenylephrine via the intra-LC route reinstated ethanol self-administration. Furthermore, lidocaine reduced ethanol self administration, but the effect was fully attenuated by noradrenaline given directly in the pVTA. This suggests that the feedback signals from LC to pVTA are necessary to sustain the ethanol self-infusion activity. Ethanol self administration significantly increased tyrosine hydroxylase immunoreactivity in pVTA and LC; the response was blocked by DSP-4 pre-treatment. While dopamine D1 , but not D2 , receptors were localized on noradrenergic LC neurons, pre-treatment with SCH-23390 (intra-LC) dampened the lever press activity. We suggest that two way communications between VTA and LC regions is essential for ethanol-triggered reinforcement behavior. PMID- 26549326 TI - Targeting intrinsically disordered proteins in rational drug discovery. AB - INTRODUCTION: Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) have gained wide recognition over the past decade due to their versatile roles in cell physiology and pathology. A large repertoire of IDPs/IDPRs has been implicated in numerous diseases, making them potential targets for therapeutic intervention. Recent advances in experimental methods and computational approaches have enabled detection and characterization of these highly dynamic proteins at atomistic detail, thus facilitating disorder/dynamic-based drug discovery. AREAS COVERED: This article presents an overview of the functional relevance and pathological implications of IDPs/IDPRs in cells. The authors outline the currently available experimental methods employed for structural characterization of these proteins. They also exemplify the practical limitations encountered during such characterization and ways to overcome them. Taken together, the article discusses the plausibility of exploiting protein disorder for drug targeting. EXPERT OPINION: Disorder-based drug targeting is gearing up in the realm of novel drug discovery approaches. Tools for probing the molecular features of IDPs and IDPRs are rapidly improving and start to provide accurate descriptions of the complex ensembles populated by IDPs/IDPRs. They thus pave the way for the development of drug molecules, which specifically target disease-associated disorder. PMID- 26549327 TI - Semiconductive Nanotube Array Constructed from Giant [Pb(II)18I54(I2)9] Wheel Clusters. AB - Crystalline nanotube array would create great opportunity for novel electrical application. Herein we report the first example of a metal halide based crystalline nanotube array which is constructed from an unprecedented giant [Pb(II)18I54(I2)9] wheel cluster, as determined by synchrotron X-ray diffraction. The electrical properties of the single crystal were studied and the present compound shows typical semiconductivity and highly anisotropic conductivity. PMID- 26549328 TI - Quantitative Proteomics Reveals Membrane Protein-Mediated Hypersaline Sensitivity and Adaptation in Halophilic Nocardiopsis xinjiangensis. AB - The genus Nocardiopsis is one of the most dominant Actinobacteria that survives in hypersaline environments. However, the adaptation mechanisms for halophilism are still unclear. Here, we performed isobaric tags for relative and absolute quantification based quantitative proteomics to investigate the functions of the membrane proteome after salt stress. A total of 683 membrane proteins were identified and quantified, of which 126 membrane proteins displayed salt-induced changes in abundance. Intriguingly, bioinformatics analyses indicated that these differential proteins showed two expression patterns, which were further validated by phenotypic changes and functional differences. The majority of ABC transporters, secondary active transporters, cell motility proteins, and signal transduction kinases were up-regulated with increasing salt concentration, whereas cell differentiation, small molecular transporter (ions and amino acids), and secondary metabolism proteins were significantly up-regulated at optimum salinity, but down-regulated or unchanged at higher salinity. The small molecule transporters and cell differentiation-related proteins acted as sensing proteins that played a more important biological role at optimum salinity. However, the ABC transporters for compatible solutes, Na(+)-dependent transporters, and cell motility proteins acted as adaptive proteins that actively counteracted higher salinity stress. Overall, regulation of membrane proteins may provide a major protection strategy against hyperosmotic stress. PMID- 26549329 TI - Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer. AB - INTRODUCTION: The aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC). MATERIALS AND METHODS: CT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed. RESULTS: Osseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis). CONCLUSION: Osseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC. PMID- 26549331 TI - Origin and Function of Tuning Diversity in Macaque Visual Cortex. AB - Neurons in visual cortex vary in their orientation selectivity. We measured responses of V1 and V2 cells to orientation mixtures and fit them with a model whose stimulus selectivity arises from the combined effects of filtering, suppression, and response nonlinearity. The model explains the diversity of orientation selectivity with neuron-to-neuron variability in all three mechanisms, of which variability in the orientation bandwidth of linear filtering is the most important. The model also accounts for the cells' diversity of spatial frequency selectivity. Tuning diversity is matched to the needs of visual encoding. The orientation content found in natural scenes is diverse, and neurons with different selectivities are adapted to different stimulus configurations. Single orientations are better encoded by highly selective neurons, while orientation mixtures are better encoded by less selective neurons. A diverse population of neurons therefore provides better overall discrimination capabilities for natural images than any homogeneous population. PMID- 26549330 TI - The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration. AB - Functional PNS regeneration requires injured axons to return to their original synaptic targets, yet the mechanisms underlying target-selective regeneration have remained elusive. Using live-cell imaging in zebrafish we find that regenerating motor axons exhibit a strong preference for their original muscle territory and that axons probe both correct and incorrect trajectories extensively before selecting their original path. We show that this process requires the glycosyltransferase lh3 and that post-injury expression of lh3 in Schwann cells is sufficient to restore target-selective regeneration. Moreover, we demonstrate that Schwann cells neighboring the transection site express the lh3 substrate collagen4a5 and that during regeneration collagen4a5 destabilizes axons probing inappropriate trajectories to ensure target-selective regeneration, possibly through the axonal repellant slit1a. Our results demonstrate that selective ECM components match subpopulations of regenerating axons with their original targets and reveal a previously unappreciated mechanism that conveys synaptic target selection to regenerating axons in vivo. VIDEO ABSTRACT. PMID- 26549333 TI - Synthesis and electrochemical properties of spherical and hollow-structured NiO aggregates created by combining the Kirkendall effect and Ostwald ripening. AB - The Kirkendall effect and Ostwald ripening were successfully combined to prepare uniquely structured NiO aggregates. In particular, a NiO-C composite powder was first prepared using a one-pot spray pyrolysis, which was followed by a two-step post-treatment process. This resulted in the formation of micron-sized spherical and hollow-structured NiO aggregates through a synergetic effect that occurred between nanoscale Kirkendall diffusion and Ostwald ripening. The discharge capacity of the spherical and hollow-structured NiO aggregates at the 500(th) cycle was 1118 mA h g(-1) and their capacity retention, which was measured from the second cycle, was nearly 100%. However, the discharge capacities of the solid NiO aggregates and hollow NiO shells were 631 and 150 mA h g(-1), respectively, at the 500(th) cycle and their capacity retentions, which were measured from the second cycle, were 63 and 14%, respectively. As such, the spherical and hollow structured NiO aggregates, which were formed through the synergetic effect of nanoscale Kirkendall diffusion and Ostwald ripening, have high structural stability during cycling and have excellent lithium storage properties. PMID- 26549332 TI - Multi-Scale Molecular Deconstruction of the Serotonin Neuron System. AB - Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. PMID- 26549335 TI - Conctact dermatitis: some important topics. AB - Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred patients with suspected ACD ranges from 27 to 95.6%. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up. PMID- 26549334 TI - An overview of fruit allergy and the causative allergens. AB - Plant allergens, being one of the most widespread allergenic substances, are hard to avoid. Hence, their identification and characterization are of prime importance for the diagnosis and treatment of food allergy. The reported allergies to fruits mainly evoke oral allergy syndrome caused by the presence of cross-reactive IgE to certain pollens and thus, allergy to fruits has also been linked to particular pollens. Many fruit allergies are being studied for their causative allergens, and are being characterized. Some tropical or exotic fruits are responsible for region-specific allergies for which only limited information is available, and generally lack allergen characterization. From a survey of the literature on fruit allergy, it is clear that some common fruits (apple, peach, musk melon, kiwi fruit, cherry, grape, strawberry, banana, custard apple, mango and pomegranate) and their allergens appear to be at the center of current research on food allergy. The present review focuses on common fruits reported as allergenic and their identified allergens; a brief description of allergens from six rare/tropical fruits is also covered. PMID- 26549336 TI - Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis. AB - BACKGROUND: Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. OBJECTIVE: To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. METHODS: We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. RESULTS: Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. CONCLUSIONS: VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung. PMID- 26549337 TI - One-year survey of paediatric anaphylaxis in an allergy department. AB - AIM: To determine the frequency of anaphylaxis in an allergy outpatient department, allowing a better understanding regarding aetiology, clinical manifestations and management, in children and adolescents. METHODS: From among 3646 patients up to 18 years old observed during one-year period, we included those with history of anaphylaxis reported by allergists. RESULTS: Sixty-four children had history of anaphylaxis (prevalence of 1.8%), with mean age 8.1+/-5.5 years, 61% being male. Median age of the first anaphylactic episode was 3 years (1 month-17 years). The majority of patients had food-induced anaphylaxis (84%): milk 22, egg 7, peanut 6, tree nuts 6, fresh fruits 6, crustaceans 4, fish 4 and wheat 2. Food-associated exercise-induced anaphylaxis was reported in 2 adolescents. Drug-induced anaphylaxis occurred in 8%: 4 non-steroidal anti inflammatory drugs and 1 amoxicillin. Three children had cold-induced anaphylaxis, one adolescent had anaphylaxis to latex and one child had anaphylaxis to insect sting. The majority (73%) had no previous diagnosis of the etiologic factor. Symptoms reported were mainly mucocutaneous (94%) and respiratory (84%), followed by gastrointestinal (42%) and cardiovascular (25%). Fifty-one patients were admitted to the emergency department, although only 33% were treated with epinephrine. Recurrence of anaphylaxis occurred in 26 patients (3 or more episodes in 14). CONCLUSIONS: In our paediatric population, the main triggering agent of anaphylaxis was IgE-mediated food allergy. Epinephrine is underused, as reported by others. Often, children have several episodes before being assessed by an allergist. We stress the importance of systematic notification and improvement of educational programmes in order to achieve a better preventive and therapeutic management of this life-threatening entity. PMID- 26549338 TI - An oral challenge test with carmine red (E120) in skin prick test positive patients. AB - BACKGROUND: Positive skin prick test reactions to carmine red (E120) occur in approximately 3% of the patients studied for food allergy. Carmine ingestion associated systemic symptoms are occasionally suspected, but sufficient information of proven carmine allergy is not available. PATIENTS AND METHODS: To analyse carmine related symptoms in skin prick test positive patients a cohort of 23 patients with suspected allergy to carmine red was subjected to a single-blind placebo-controlled oral challenge test with carmine red. RESULTS: Five patients developed clinical symptoms during the placebo-controlled oral challenge. As a result, the overall frequency of clinical carmine allergy is estimated to be 0.7% in general dermatology patients studied for food-associated symptoms. CONCLUSIONS: Oral challenge test provides a valuable in vivo tool to better inform patients with positive skin prick tests to additives to avoid false allergy diets. PMID- 26549339 TI - Detection of risk factors for systemic adverse reactions to SCIT with natural depot allergen extracts: a retrospective study. AB - BACKGROUND: Some patients seem to show a particular propensity to experience systemic reactions (SR) when undergoing SCIT. This study looked at their features. METHODS: 423 adults submitted to subcutaneous immunotherapy (SCIT) with 583 depot allergens extracts were studied. A "slow" build-up schedule was followed, and maintenance doses were given monthly. No mixtures of allergens were employed; multi-sensitized patients were treated with two extracts at the same time. IgE to pollen allergen components were measured. Patients experiencing several SR and those showing repeated large local reactions preventing up dosing were analyzed. RESULTS: Altogether, 14% of patients experienced at least 2 SR to SCIT and further 13% repeated local reactions. All SR involved the skin. Eight treatments were stopped. No reactor was using beta-blockers. SR were not associated with pollen season, use of freshly prepared vials, administration of 2 allergens, or extract producer, nor were preceded by large local reactions. Reactors were younger than tolerant subjects (p<0.05), and females were less frequently fully tolerant than males (p<0.001). The multiple regression analysis showed that both ragweed and grass SCIT were significantly associated with adverse reactions (p<0.001). Specific IgE to Amb a 1 or Phl p 1 did not differ statistically between reactors and tolerant subjects, whereas grass pollen allergic reactors showed higher levels of IgE to Phl p 5. Intolerance did not depend on the number of primary sensitizations or on hypersensitivity to pollen pan-allergens. CONCLUSION: Young patients or women hypersensitive to grass and ragweed pollen seem at higher risk for SR during SCIT. PMID- 26549340 TI - Allergenicity of Artemisia contained in bee pollen is proportional to its mass. AB - Bee product mugwort is identified as being at the origin of allergic accidents but the biological potency of Artemisia contained in bee pollen is not well known. In this experiment, Artemisia mass was identified in bee pollen mass and after having calculated the proportion of Artemisia using the bee pollen melissopalynology spectrum. Skin reactivity to Artemisia was assessed by measuring wheal diameters (W) from skin prick tests using three serial dilutions of bee pollen on 11 allergic patients to Artemisia, in order to calculate the relationship between Artemisia mass (Massartemisia) in bee pollen and skin reactivity. The dose-response power regression curve (Wartemisia)=3.328 (Massartemisia)0.297 (R2=0.9947) and the linear function Log10 (Wartemisia)=0.297 (Log10 (Massartemisia)+0.520 (R=0.9974)) were established using a bee pollen sample with 0.246 mg of Artemisia pollen per mg. Mugwort allergens seem to be little or not altered by bee secretions and bee pollen retains its allergenic capacity. To our knowledge this is the first time it has been shown that skin reactivity of patients allergic to mugwort is proportional to the absolute mugwort mass contained in the bee pollen. PMID- 26549341 TI - An unusual case of delayed-type hypersensitivity to ceftriaxone and meropenem. AB - Recent studies have demonstrated a low cross-reactivity between beta-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity of meropenem in patients with non-immediate hypersensitivity to cephalosporins. We describe a case of a 13-year-old male, admitted in Neurosurgery with a severe extradural empyema complicating frontal sinusitis, submitted to an emergent bifrontal craniotomy. A generalized maculopapular exanthema, fever and malaise, appeared by the 7th day of meningeal doses of ceftriaxone, clindamycin and vancomycin. Those were replaced by meropenem, with posterior worsening of the reaction and mucosal involvement. A new scheme with amikacin, metronidazole and linezolid was done with improvement. Skin prick, intradermal and patch tests to penicillins, ceftriaxone and meropenem were negative. Lymphocyte transformation test was positive to ceftriaxone and negative to meropenem.Non-immediate T cell mechanism seems to be involved. Diagnosis work up couldn't exclude cross-reactivity between ceftriaxone and meropenem. PMID- 26549342 TI - Eosinophilic Granulomatosis with Polyangiitis preceding allergic bronchopulmonary aspergillosis. AB - A 61-year-old Chinese man with long-standing, stable Eosinophilic Granulomatosis with Polyangiitis (EGPA) and asthma, presented with acute hypoxemia and declining obstructive pulmonary function. Elevated serum IgE levels, positive Aspergillus fumigatus specific IgE and CT findings of central bronchiectasis with small airway mucoid impaction confirmed new development of Allergic Bronchopulmonary Aspergillosis (ABPA). The maintenance therapy for EGPA, azathioprine, was discontinued. Prednisolone 0.5 mg/kg/day and Itraconazole improved his symptoms and IgE levels. To our knowledge, ABPA occurring in a patient with EGPA has not been reported. Differentiation of EGPA with asthmatic flare vs ABPA vs asthma with aspergillus hypersensitivity is discussed. Heightened Th2 immunity where eosinophils play a central role may link these conditions. PMID- 26549343 TI - Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan. AB - Canine progressive rod-cone degeneration (PRCD) is a middle- to late-onset, autosomal recessive, inherited retinal disorder caused by a substitution (c.5G>A) in the canine PRCD gene that has been identified in 29 or more purebred dogs. In the present study, a TaqMan probe-based real-time PCR assay was developed and evaluated for rapid genotyping and large-scale screening of the mutation. Furthermore, a genotyping survey was carried out in a population of the three most popular breeds in Japan (Toy Poodles, Chihuahuas and Miniature Dachshunds) to determine the current mutant allele frequency. The assay separated all the genotypes of canine PRCD rapidly, indicating its suitability for large-scale surveys. The results of the survey showed that the mutant allele frequency in Toy Poodles was high enough (approximately 0.09) to allow the establishment of measures for the prevention and control of this disorder in breeding kennels. The mutant allele was detected in Chihuahuas for the first time, but the frequency was lower (approximately 0.02) than that in Toy Poodles. The mutant allele was not detected in Miniature Dachshunds. This assay will allow the selective breeding of dogs from the two most popular breeds (Toy Poodle and Chihuahua) in Japan and effective prevention or control of the disorder. PMID- 26549344 TI - Epigenetic regulation of IQGAP2 promotes ovarian cancer progression via activating Wnt/beta-catenin signaling. AB - Ovarian cancer is the most lethal gynecologic malignancy and most cases are diagnosed at an advanced stage with metastases; however, the molecular events supporting ovarian cancer development and progression remain poorly understood. In this study, by analysis of the genome-scale DNA methylation profiles of 8 healthy ovaries, 89 ovarian cancers and the corresponding 4 normal ovaries from The Cancer Genome Atlas, we unveiled the abnormalities in gene methylation of ovarian cancers, and found that IQGAP2 one of the most frequently altered genes, was significantly hypermethylated in ovarian cancer. There was an inverse correlation between IQGAP2 DNA methylation and mRNA expression, and IQGAP2 expression was downregulated in ovarian cancer. Further survival analysis indicated that decreased IQGAP2 was associated with a worse progression-free survival of patient with ovarian cancer, and biological function studies demonstrated that IQGAP2 inhibited ovarian cancer cell epithelial-mesenchymal transition, migration and invasion via suppression of Wnt-induced beta-catenin nuclear translocation and transcriptional activity. Thus, these data identified IQGAP2 as a novel tumor suppressor for ovarian cancer to inhibit cell invasion through regulating Wnt/beta-catenin signaling, and provided a new biomarker and potential therapeutic strategy for this disease. PMID- 26549345 TI - The stabilisation of the Nx phase in mixtures. AB - The phase behaviour of mixtures between two symmetric dimers, CBC9CB and the ether-linked analogue CBOC9OCB was investigated by Polarizing Optical Microscopy (POM), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies. The dimeric constituents are fully miscible and the construction of a temperature-composition phase diagram reveals a surprising amplification of the stability of the Nx phase in compositions of up to 37 wt% of CBOC9OCB in CBC9CB. The origin for this enhancement of stability is discussed and an explanation based on chiral recognition is developed. PMID- 26549346 TI - The neural dynamics of sensory focus. AB - Coordinated sensory and motor system activity leads to efficient localization behaviours; but what neural dynamics enable object tracking and what are the underlying coding principles? Here we show that optimized distance estimation from motion-sensitive neurons underlies object tracking performance in weakly electric fish. First, a relationship is presented for determining the distance that maximizes the Fisher information of a neuron's response to object motion. When applied to our data, the theory correctly predicts the distance chosen by an electric fish engaged in a tracking behaviour, which is associated with a bifurcation between tonic and burst modes of spiking. Although object distance, size and velocity alter the neural response, the location of the Fisher information maximum remains invariant, demonstrating that the circuitry must actively adapt to maintain 'focus' during relative motion. PMID- 26549347 TI - Dynamic regulation of stem cell specification and maintenance by hypoxia inducible factors. AB - Stem cells are characterized by the capacity for both self-renewal and generation of all other cell types (pluripotency) or differentiated cells within a particular lineage (multipotency). Stem cells are often localized to hypoxic niches within tissues and hypoxia inducible factors (HIFs) play key roles in the maintenance of pluripotent and multipotent stem cells, as well as cancer stem cells, which are also known as tumor-initiating cells. HIF inhibitors target cancer stem cells and improve the responses to angiogenesis inhibitors and cytotoxic chemotherapy in mouse models of breast cancer. PMID- 26549349 TI - The Experience of Male Nursing Students. AB - PURPOSE: To explore the experience of male nursing students in a baccalaureate nursing program. METHODS: This study used a qualitative approach with content analysis. Written narratives in response to open-ended questions were analyzed. Lincoln and Guba's guidelines were followed. SETTING AND POPULATION: This study took two academic years to complete, at a baccalaureate nursing program in the northeast United States. It consisted of 23 male undergraduate nursing students who had completed three clinical nursing courses. FINDINGS: Five themes emerged from the data analysis: staying focused, opinions matter, I want to be "a nurse," relationships, and looking ahead. CONCLUSIONS: The male nursing students in this study were serious about entering the nursing profession. They wanted to be known as "nurses," not "male nurses." Additional findings from this study can provide educators and clinicians with a deeper understanding of the experiences of male nursing students and what they need to be successful. DeVito. PMID- 26549350 TI - Wilson disease: Health-related quality of life and risk for depression. AB - BACKGROUND: Wilson disease is an autosomal recessive disorder of copper metabolism and requires lifelong medical treatment. Therefore, the analysis of quality of life has gathered more attention. Aims of this study were to examine risk for depression and health-related quality of life in patients suffering from Wilson disease. METHODS: Sixty-eight patients were included in this retrospective cross sectional study. The Personal Health Questionnaire-9 Depression Scale was used to assess depression. The Short Form-36 Health Survey questionnaire was used to assess health-related quality of life. RESULTS: The Personal Health Questionnaire-9 indicated that 21% (14/68) of patients were at risk for major depressive disorders (scores>10) and 35% (24/68) were at risk for mild depression (scores 5-9). Women had significantly lower life quality scores than men. Primary neurologic disease manifestation was associated with significantly lower total Short Form-36 and subdimension scores compared with primary hepatic or mixed presentation. Overall, patients with Wilson disease experienced higher quality of life than patients with other chronic liver diseases. CONCLUSIONS: As patients with Wilson disease have a high risk for depressive disorders, active assessment for depression is mandatory. Patients with primary neurological symptoms are at higher risk for reduction of life quality. PMID- 26549351 TI - A Meshless Algorithm to Model Field Evaporation in Atom Probe Tomography. AB - An alternative approach for simulating the field evaporation process in atom probe tomography is presented. The model uses the electrostatic Robin's equation to directly calculate charge distribution over the tip apex conducting surface, without the need for a supporting mesh. The partial ionization state of the surface atoms is at the core of the method. Indeed, each surface atom is considered as a point charge, which is representative of its evaporation probability. The computational efficiency is ensured by an adapted version of the Barnes-Hut N-body problem algorithm. Standard desorption maps for cubic structures are presented in order to demonstrate the effectiveness of the method. PMID- 26549348 TI - Molecular pathophysiology of hepatic glucose production. AB - Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM. PMID- 26549352 TI - Progenitor cells may aid successful islet compensation in metabolically healthy obese individuals. AB - Obesity is associated with insulin resistance and type 2 diabetes. Fortunately most obese, insulin-resistant individuals do not develop type 2 diabetes as they can overcome reduced efficiency of insulin action by increasing the functional beta-cell mass. Compelling evidences suggest beta-cells neogenesis through progenitor/stem cells residing in pancreatic ductal cells and islets, but the role of beta-cell regeneration in obesity/insulin resistance from progenitor/stem cells is not clear. Based on many indirect evidences in human studies such as unchanged beta-cell replication, apoptosis and size during compensation in insulin resistance in humans, we suggest successful beta-cells mass compensation in metabolically healthy obesity is contributed by neoformation of beta-cells, through expansion of progenitor cells/stem cells in synergy with beta-cell replication. PMID- 26549353 TI - A novel function of the human oncogene Stil: Regulation of PC12 cell toxic susceptibility through the Shh pathway. AB - The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in vertebrate species. Here, we report new findings of Stil in the regulation of toxic susceptibility in mammalian dopaminergic (DA)-like PC12 cells. RNAi mediated knockdown of Stil expression did not affect the survival of proliferating PC12 cells but caused a significant amount of cell death in differentiated neurons after toxic drug treatment. In contrast, overexpression of Stil increased toxic susceptibility only in proliferating cells but produced no effect in mature neurons. Exogenetic inactivation or activation of the Sonic hedgehog (Shh) signaling transduction mimicked the effect of Stil knockdown or overexpression in regulation of PC12 cell toxic susceptibility, suggesting that Stil exerts its role through the Shh pathway. Together, the data provide evidence for novel functions of the human oncogene Stil in neural toxic susceptibility. PMID- 26549354 TI - Development of viscoelastic stability of resin-composites incorporating novel matrices. AB - OBJECTIVES: To study the effect of resin matrix and maturation time (1 and 24 h) on the creep deformation of resin-composites, two of which have matrix-forming monomers that are either bis-GMA free or have an ormocer structure between the CC groups. METHODS: Five resin-composites: four commercial and one experimental were investigated. Six specimens were prepared for each material and were divided into two groups (n=3) according to the maturation time and condition. Group A was stored dry at room temperature for 1 h and Group B was stored for 24 h in distilled water to allow post-curing at 37 degrees C. Each specimen was loaded (20 MPa) for 2 h and unloaded for 2 h. The strain deformation was recorded continuously for 4h. Statistical analysis was performed using one-way ANOVA and the Bonferroni post hoc test at a significance level of a=0.05. RESULTS: The maximum creep-strain % after 1 h ranged from 1.32% to 2.50% and was reduced after 24h post-cure to between 0.66% and 1.47%. Also, the permanent set after 1h ranged from 0.70% up to 1.27% (Group A) and after 24 h ranged from 0.53% up to 1.20% (Group B). SIGNIFICANCE: Creep deformation and maximum recovery for all resin composites decreased with time, demonstrating improvement in viscoelastic stability. However, there was no significant difference between the permanent set at different times, except for Herculite XRV Ultra. Composites with novel matrices showed comparable properties to existing bis-GMA based materials. PMID- 26549355 TI - Influence of hydroxyethyl acrylamide addition to dental adhesive resin. AB - OBJECTIVE: to determine the physicochemical properties of experimental adhesive resins containing hydroxyethyl acrylamide. METHODS: Three groups of experimental resin were formulated, GHEAA33% (33.3wt% HEAA+66.6wt% BisGMA), GHEAA50% (50wt% HEAA+50wt% BisGMA), and GHEAA-FREE (33.3wt% HEMA+66.6wt% of BisGMA). The polymerization process of each adhesive resin group, as well as for the homopolymers, BisGMA, HEMA, HEAA, HEMA* without EDAB, and HEAA* without EDAB, was characterized through differential scanning calorimetry (DSC). Elution of monomers was evaluated by (1)H NMR. Dynamic mechanical analysis (DMA) was used to collect the glass transition temperature (Tg), the storage modulus (E') and the reticulation degree (rho). Flexural strength was calculated by three-point bending test with 0.75mm/min. Softening in solvent was calculated through hardness before and after immersion in water or ethanol. RESULTS: GHEAA50%, GHEAA33%, GHEAA-FREE presented higher polymerization rate ( [Formula: see text] , 12.3 and 5.3mmolg(-1)s(-1), respectively) than homopolymers HEMA, HEMA* and HEAA*. Group with HEAA presented higher degree of conversion (GHEAA50%=64.07%>GHEAA33%=55.82%>GHEAA-FREE=49.02%; p=0.008) All groups presented low elution of monomers (p>0.05). The values of E' were higher on GHEAA33% than GHEAA-FREE (p=0.034). Tg and flexural strength values of GHEAA-FREE were higher than acrylamide groups (p=0.022 and p<0.001, respectively). Hardness varied from 27.05 to 34.78 for water and from 63.27 to 68.51 for ethanol with no difference for rho values. SIGNIFICANCE: The addition of HEAA increased the materials reactivity and, consequently, improved the maximum rate of polymerization, degree of conversion and the storage modulus of experimental adhesive resin. PMID- 26549356 TI - Staying young at heart: autophagy and adaptation to cardiac aging. AB - Aging is a predominant risk factor for developing cardiovascular disease. Therefore, the cellular processes that contribute to aging are attractive targets for therapeutic interventions that can delay or prevent the development of age related diseases. Our understanding of the underlying mechanisms that contribute to the decline in cell and tissue functions with age has greatly advanced over the past decade. Classical hallmarks of aging cells include increased levels of reactive oxygen species, DNA damage, accumulation of dysfunctional organelles, oxidized proteins and lipids. These all contribute to a progressive decline in the normal physiological function of the cell and to the onset of age-related conditions. A major cause of the aging process is progressive loss of cellular quality control. Autophagy is an important quality control pathway and is necessary to maintain cardiac homeostasis and to adapt to stress. A reduction in autophagy has been observed in a number of aging models and there is compelling evidence that enhanced autophagy delays aging and extends life span. Enhancing autophagy counteracts age-associated accumulation of protein aggregates and damaged organelles in cells. In this review, we discuss the functional role of autophagy in maintaining homeostasis in the heart, and how a decline is associated with accelerated cardiac aging. We also evaluate therapeutic approaches being researched in an effort to maintain a healthy young heart. PMID- 26549357 TI - Interleukin-10 inhibits chronic angiotensin II-induced pathological autophagy. AB - BACKGROUND: Although autophagy is an essential cellular salvage process to maintain cellular homeostasis, pathological autophagy can lead to cardiac abnormalities and ultimately heart failure. Therefore, a tight regulation of autophagic process would be important to treat chronic heart failure. Previously, we have shown that IL-10 strongly inhibited pressure overload-induced hypertrophy and heart failure, but role of IL-10 in regulation of pathological autophagy is unknown. Here we tested the hypothesis that IL-10 inhibits angiotensin II-induced pathological autophagy and this process, in part, leads to improve cardiac function. METHODS AND RESULTS: Chronic Ang II strongly induced mortality, cardiac dysfunction in IL-10 Knockout mice. IL-10 deletion exaggerated pathological autophagy in response to Ang II treatment. In isolated cardiac myocytes, IL-10 attenuated Ang II-induced pathological autophagy and activated Akt/mTORC1 signaling. Pharmacological or molecular inhibition of Akt and mTORC1 signaling attenuated IL-10 effects on Ang II-induced pathological autophagy. Furthermore, lysosomal inhibition in autophagic flux experiments further confirmed that IL-10 inhibits pathological autophagy via mTORC1 signaling. CONCLUSION: Our data demonstrate a novel role of IL-10 in regulation of pathological autophagy; thus can act as a potential therapeutic molecule for treatment of chronic heart disease. PMID- 26549359 TI - The effectiveness of influenza vaccination in preventing hospitalisation in children in Western Australia. AB - BACKGROUND: There is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory confirmed influenza-associated hospitalisation in children. PATIENTS AND METHODS: Laboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010-2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models. RESULTS: Three hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B, 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1-4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: -6.6%, 86.7%). CONCLUSION: In this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children. PMID- 26549358 TI - Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy. AB - Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cepsilon (PKCepsilon) mouse model of DCM. Transgenic mice expressing constitutively active PKCepsilon in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCepsilon mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCepsilon mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCepsilon mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCepsilon mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted. PMID- 26549360 TI - A chicken homologue of nectin-4 functions as a measles virus receptor. AB - Measles virus (MV) vaccine strains use CD46, signaling lymphocyte activation molecule, and nectin-4 in human cells as receptors. Meanwhile, many of them are propagated in primary chicken embryonic fibroblasts (CEFs). Our data revealed that CEFs express a nectin-4 homologous molecule (CEF nectin-4) containing well conserved motifs in the FG and BC loops, but not in the C'C" loop. MV infected CHO cells expressing CEF nectin-4 and induced syncytia in these cells, confirming that CEF nectin-4 functions as an MV receptor and that the C'C" loop is not critical for this function. Nectin-4-blind mutations in MV H protein reduced the infectivity of MV in CEF nectin-4-expressing cells. Infection of CEFs with the MV vaccine AIK-C strain was partially blocked by an anti-nectin-4 antibody, indicating that CEF nectin-4 plays a role for propagation of MV vaccines in CEFs. PMID- 26549362 TI - Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine. AB - The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6 14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine. PMID- 26549361 TI - Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008-2011. AB - BACKGROUND: To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9-26 years of age in the Vaccine Safety Datalink. METHODS: We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1-60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma. RESULTS: We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n=3) and 9-12 year olds (n=4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1-60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47-4.64) in the 1-7 days following HPV4 exposure to 0.92 (95% CI: 0.54-1.57) in the 1-60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure. CONCLUSION: The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis. PMID- 26549363 TI - Mass vaccination with a two-dose oral cholera vaccine in a long-standing refugee camp, Thailand. AB - BACKGROUND: During 2005-2012, surveillance in Maela refugee camp, Thailand, identified four cholera outbreaks, with rates up to 10.7 cases per 1000 refugees. In 2013, the Thailand Ministry of Public Health sponsored a two-dose oral cholera vaccine (OCV) campaign for the approximately 46,000 refugees living in Maela. METHODS: We enumerated the target population (refugees living in Maela who are >=1 year old and not pregnant) in a census three months before the campaign and issued barcoded OCV cards to each individual. We conducted the campaign using a fixed-post strategy during two eight-day rounds plus one two-day round for persons who had missed their second dose and recorded vaccine status for each individual. To identify factors associated with no vaccination (versus at least one dose) and those associated with adverse events following immunization (AEFI), we used separate marginal log-binomial regression models with robust variance estimates to account for household clustering. RESULTS: A total of 63,057 OCV doses were administered to a target population of 43,485 refugees. An estimated 35,399 (81%) refugees received at least one dose and 27,658 (64%) received two doses. A total of 993 additional doses (1.5%) were wasted including 297 that were spat out. Only 0.05% of refugees, mostly children, could not be vaccinated due to repeated spitting. Characteristics associated with no vaccination (versus at least one dose) included age >=15 years (versus 1-14 years), Karen ethnicity (versus any other ethnicity) and, only among adults 15-64 years old, male sex. Passive surveillance identified 84 refugees who experienced 108 AEFI including three serious but coincidental events. The most frequent AEFI were nausea (49%), dizziness (38%), and fever (30%). Overall, AEFI were more prevalent among young children and older adults. CONCLUSIONS: Our results suggest that mass vaccination in refugee camps with a two-dose OCV is readily achievable and AEFI are few. PMID- 26549364 TI - Evaluation of the risk of venous thromboembolism after quadrivalent human papillomavirus vaccination among US females. AB - After the Food and Drug Administration (FDA) licensed quadrivalent human papillomavirus vaccine (HPV4) in 2006, reports suggesting a possible association with venous thromboembolism (VTE) emerged from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink. Our objective was to determine whether HPV4 increased VTE risk. The subjects were 9-26-year-old female members of five data partners in the FDA's Mini-Sentinel pilot project receiving HPV4 during 2006-2013. The outcome was radiologically confirmed first-ever VTE among potential cases identified by diagnosis codes in administrative data during Days 1-77 after HPV4 vaccination. With a self-controlled risk interval design, we compared counts of first-ever VTE in risk intervals (Days 1-28 and Days 1-7 post vaccination) and control intervals (Days 36-56 for Dose 1 and Days 36-63 for Doses 2 and 3). Combined hormonal contraceptive use was treated as a potential confounder. The main analyses were: (1) unadjusted for time-varying VTE risk from contraceptive use, (2) unadjusted but restricted to cases without such time varying risk, and (3) adjusted by incorporating the modeled risk of VTE by week of contraceptive use in the analysis. Of 279 potential VTE cases identified following 1,423,399 HPV4 doses administered, 225 had obtainable charts, and 53 were confirmed first-ever VTE. All 30 with onsets in risk or control intervals had known risk factors for VTE. VTE risk was not elevated in the first 7 or 28 days following any dose of HPV in any analysis (e.g. relative risk estimate (95% CI) from both unrestricted analyses, for all-doses, 28-day risk interval: 0.7 (0.3-1.4)). Temporal scan statistics found no clustering of VTE onsets after any dose. Thus, we found no evidence of an increased risk of VTE associated with HPV4 among 9-26-year-old females. A particular strength of this evaluation was its control for both time-invariant and contraceptive-related time-varying potential confounding. PMID- 26549365 TI - Increasing postpartum rate of vaccination with tetanus, diphtheria, and acellular pertussis vaccine by incorporating pertussis cocooning information into prenatal education for group B streptococcus prevention. AB - BACKGROUND: To evaluate whether incorporating pertussis cocooning information into prenatal education for group B streptococcus (GBS) prevention increased postpartum rate of vaccination with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine. METHODS: We performed a retrospective pre-intervention/post intervention study of postpartum women at a teaching hospital in Taiwan. We compared the frequency of Tdap vaccination during the pre-intervention (May 1, 2009 to December 31, 2010) and post-intervention (March 1, 2011-March 31, 2012) time periods. The clinical intervention was incorporation of pertussis cocooning information into prenatal education for GBS prevention to pregnant women presented during a prenatal visit at 35-37 weeks of gestation. Postpartum Tdap vaccination rate during the pre-intervention and post-intervention periods was compared. We also specifically examined group differences in the percentage of women who received postpartum Tdap vaccination to explore factors that influenced their decision regarding Tdap vaccine. RESULTS: Tdap vaccination was more likely during the post-intervention period compared with the pre-intervention period (2268 of 3186 [71.2%] compared with 2556 of 5030 [55.6%]; p<.001). Comparisons between each subgroup of pre-intervention and post-intervention women showed that incorporating pertussis information into prenatal education for GBS prevention was beneficial except for women of maternal age 30-34 years and women living in rural areas. CONCLUSIONS: Prenatal GBS screening activities represent an opportunity for healthcare providers to offer pertussis cocooning information to eligible pregnant women to improve rates of postpartum Tdap vaccination. PMID- 26549366 TI - Phenotypic characterization of bovine memory cells responding to mycobacteria in IFNgamma enzyme linked immunospot assays. AB - Bovine tuberculosis (bTB) remains a globally significant veterinary health problem. Defining correlates of protection can accelerate the development of novel vaccines against TB. As the cultured IFNgamma ELISPOT (cELISPOT) assay has been shown to predict protection and duration of immunity in vaccinated cattle, we sought to characterize the phenotype of the responding T-cells. Using expression of CD45RO and CD62L we purified by cytometric cell sorting four distinct CD4(+) populations: CD45RO(+)CD62L(hi), CD45RO(+)CD62L(lo), CD45RO( )CD62L(hi) and CD45RO(-)CD62L(lo) (although due to low and inconsistent cell recovery, this population was not considered further in this study), in BCG vaccinated and Mycobacterium bovis infected cattle. These populations were then tested in the cELISPOT assay. The main populations contributing to production of IFNgamma in the cELISPOT were of the CD45RO(+)CD62L(hi) and CD45RO(+)CD62L(lo) phenotypes. These cell populations have been described in other species as central and effector memory cells, respectively. Following in vitro culture and flow cytometry we observed plasticity within the bovine CD4(+) T-cell phenotype. Populations switched phenotype, increasing or decreasing expression of CD45RO and CD62L within 24h of in vitro stimulation. After 14 days all IFNgamma producing CD4(+) T cells expressed CD45RO regardless of the original phenotype of the sorted population. No differences were detected in behavior of cells derived from BCG-vaccinated animals compared to cells derived from naturally infected animals. In conclusion, although multiple populations of CD4(+) T memory cells from both BCG vaccinated and M. bovis infected animals contributed to cELISPOT responses, the dominant contributing population consists of central-memory-like T cells (CD45RO(+)CD62L(hi)). PMID- 26549368 TI - 4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90alpha chaperone activity against prostate cancer. AB - Histone deacetylase (HDAC)6 is a unique isoenzyme targeting specific substrates including alpha-tubulin and heat shock protein (HSP)90. HDAC6 is involved in protein trafficking and degradation, cell shape and migration. Deregulation of HDAC6 activity is associated with a variety of diseases including cancer leading to a growing interest for developing HDAC6 inhibitors. Here, we identified two new structurally related 4-hydroxybenzoic acids as selective HDAC6 inhibitors reducing proliferation, colony and spheroid formation as well as viability of prostate cancer cells. Both compounds strongly enhanced alpha-tubulin acetylation leading to remodeling of microtubular organization. Furthermore, 4-hydroxybenzoic acids decreased HSP90alpha regulation of the human androgen receptor in prostate cancer cells by increasing HSP90alpha acetylation levels. Collectively, our data support the potential of 4-hydroxybenzoic acid derivatives as HDAC6-specific inhibitors with anti-cancer properties. PMID- 26549369 TI - Missing links: testing the completeness of host-parasite checklists. AB - Host-parasite checklists are essential resources in ecological parasitology, and are regularly used as sources of data in comparative studies of parasite species richness across host species, or of host specificity among parasite species. However, checklists are only useful datasets if they are relatively complete, that is, close to capturing all host-parasite associations occurring in a particular region. Here, we use three approaches to assess the completeness of 25 checklists of metazoan parasites in vertebrate hosts from various geographic regions. First, treating checklists as interaction networks between a set of parasite species and a set of host species, we identify networks with a greater connectance (proportion of realized host-parasite associations) than expected for their size. Second, assuming that the cumulative rise over time in the number of known host-parasite associations in a region tends toward an asymptote as their discovery progresses, we attempt to extrapolate the estimated total number of existing associations. Third, we test for a positive correlation between the number of published reports mentioning an association and the time since its first record, which is expected because observing and reporting host-parasite associations are frequency-dependent processes. Overall, no checklist fared well in all three tests, and only three of 25 passed two of the tests. These results suggest that most checklists, despite being useful syntheses of regional host parasite associations, cannot be used as reliable sources of data for comparative analyses. PMID- 26549367 TI - Inhibition of Kv channel expression by NSAIDs depolarizes membrane potential and inhibits cell migration by disrupting calpain signaling. AB - Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is well known to cause gastrointestinal ulcer formation via several mechanisms that include inhibiting epithelial cell migration and mucosal restitution. The drug-affected signaling pathways that contribute to inhibition of migration by NSAIDs are poorly understood, though previous studies have shown that NSAIDs depolarize membrane potential and suppress expression of calpain proteases and voltage-gated potassium (Kv) channel subunits. Kv channels play significant roles in cell migration and are targets of NSAID activity in white blood cells, but the specific functional effects of NSAID-induced changes in Kv channel expression, particularly on cell migration, are unknown in intestinal epithelial cells. Accordingly, we investigated the effects of NSAIDs on expression of Kv1.3, 1.4, and 1.6 in vitro and/or in vivo and evaluated the functional significance of loss of Kv subunit expression. Indomethacin or NS-398 reduced total and plasma membrane protein expression of Kv1.3 in cultured intestinal epithelial cells (IEC 6). Additionally, depolarization of membrane potential with margatoxin (MgTx), 40mM K(+), or silencing of Kv channel expression with siRNA significantly reduced IEC-6 cell migration and disrupted calpain activity. Furthermore, in rat small intestinal epithelia, indomethacin and NS-398 had significant, yet distinct, effects on gene and protein expression of Kv1.3, 1.4, or 1.6, suggesting that these may be clinically relevant targets. Our results show that inhibition of epithelial cell migration by NSAIDs is associated with decreased expression of Kv channel subunits, and provide a mechanism through which NSAIDs inhibit cell migration and may contribute to NSAID-induced gastrointestinal (GI) toxicity. PMID- 26549370 TI - Preparation of Radiopaque Drug-Eluting Beads for Transcatheter Chemoembolization. AB - PURPOSE: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. MATERIALS AND METHODS: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 um bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. RESULTS: Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. CONCLUSIONS: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques. PMID- 26549371 TI - Cone-Beam CT Angiography for Determination of Tumor-Feeding Vessels During Chemoembolization of Liver Tumors: Comparison of Conventional and Dedicated Software Analysis. AB - PURPOSE: To compare the ability of dedicated software and conventional cone-beam computed tomography (CT) analysis to identify tumor-feeding vessels in hypervascular liver tumors treated with chemoembolization. MATERIAL AND METHODS: Between January 2012 and January 2013, 45 patients (32 men, mean age of 61 y; range, 27-85 y) were enrolled, and 66 tumors were treated (mean, 32 mm +/- 18; range, 10-81 mm) with conventional chemoembolization with arterial cone-beam CT. Data were independently analyzed by six interventional radiologists with standard postprocessing software, a computer-aided analysis with FlightPlan for liver (FPFL; ie, "raw FPFL"), and a review of this computer-aided FPFL analysis ("reviewed FPFL"). Analyses were compared with a reference reading established by two study supervisors in consensus who had access to all imaging data. Sensitivities, positive predictive values (PPVs), and false-positive (FP) ratios were compared by McNemar, chi(2), and Fisher exact tests. Analysis durations were compared by Mann-Whitney test, and interreader agreement was assessed. RESULTS: Reference reading identified 179 feeder vessels. The sensitivity of raw FPFL was significantly higher than those of reviewed FPFL and conventional analyses (90.9% vs 83.2% and 82.1%; P < .0001), with lower PPV (82.9% vs 91.2% and 90.6%, respectively; P < .0001), higher FP ratio (17.1% vs 9.4% and 8.8%, respectively; P < .0001), and greater interreader agreement (92% vs 80% and 79%, respectively; P < .0001). Reviewed FPFL analysis took significantly longer than both other analyses (P < .0001). CONCLUSIONS: The FPFL analysis software enabled a fast, accurate, and sensitive detection of tumor feeder vessels. PMID- 26549372 TI - Rac1 mediates HMGB1-induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction. AB - The pathology of acute respiratory distress syndrome (ARDS) is closely associated with the failure of alveolar-capillary barrier integrity and alveolar filling by high protein pulmonary edema, resulting from hyperpermeability. High mobility group box 1 (HMGB1) is a novel late mediator of sepsis, which is specifically involved in endotoxin-induced acute lung injury and sepsis-associated lethality. Although the role of HMGB1 in endothelial cell cytoskeletal rearrangement and vascular permeability have been investigated preliminarily, the molecular mechanisms remain to be fully elucidated. As the ras-related C3 botulinum toxin substrate 1 (Rac1) gene is important role in regulating microvascular barrier maintenance, the present study was designed to determine whether Rac1 is involved in HMGB1-induced hyperpermeability in pulmonary microvascular endothelial cells (PMVECs). The results of the present study demonstrated that HMGB1 induced dose and time-dependent decreases in transendothelial electrical resistance (TER). Notably, HMGB1 induced a dose-dependent increase in the activity and expression levels of Rac1. Using small interfering RNA and an agonist of Rac1, the present study demonstrated that Rac1 was a novel factor mediating the HMGB1-induced decrease in TER via extracellular signal-regulated kinase and p38 mitogen activated protein kinase (MAPK) activation. These data suggested that Rac1 is involved in HMGB1-induced hyperpermeability in PMVECs via MAPK signal transduction. PMID- 26549373 TI - Transaortic transcatheter aortic valve implantation using the Lotus valve: first in-man experience. AB - AIMS: To demonstrate the feasibility of implanting the Lotus second-generation transcatheter heart valve (THV) (designed for a transfemoral procedure) via a transaortic approach. METHODS AND RESULTS: We describe a case with severe aortic stenosis in the presence of small calibre and calcified femoral access and severe chronic obstructive pulmonary disease. The transaortic approach was the ideal approach for this patient and we successfully implanted a 25 mm Lotus valve without any complication. CONCLUSIONS: The transaortic access is a feasible and safe alternative in patients who have suboptimal iliofemoral conduits and who will benefit from the unique features of the Lotus THV. PMID- 26549374 TI - Incidence and potential mechanism of resolved, persistent and newly acquired malapposition three days after implantation of self-expanding or balloon expandable stents in a STEMI population: insights from optical coherence tomography in the APPOSITION II study. AB - AIMS: The aim of the current study was to investigate the frequency and mechanisms of sequential incomplete stent apposition (ISA) changes such as persistent, resolved or newly acquired ISA during the first three days after primary PCI (pPCI) in a matched segment-level analysis, with the comparison between self-expanding and balloon-expandable stents assessed by optical coherence tomography (OCT). METHODS AND RESULTS: The current analysis is a substudy of the APPOSITION II study that included 69 patients (self-expanding: 35, balloon-expandable: 34) using serial optical coherence tomography (OCT) post procedure and three days after pPCI. In order to evaluate a temporal change in ISA, stented regions were segmented using fiduciary landmarks. In a total of 228 corresponding segments, persistent and newly acquired ISA were less frequently observed in self-expanding stents than in balloon-expandable stents (11.5% vs. 33.9%, p<0.01, 2.7% vs. 14.8%, p<0.01, respectively). New appearances of ISA were caused by tissue resorption, vasorelaxation and "early" recoil in balloon expandable stents, and only tissue resorption in self-expanding stents. CONCLUSIONS: Three days after pPCI, tissue resorption and vasorelaxation were biological factors associated with new appearance of ISA while "early" recoil of balloon-expandable stents was a mechanical factor. Both persistent ISA and newly acquired ISA occurred less frequently in self-expanding stents, resulting in a low number of ISA segments compared to balloon-expandable stents. Clinical Trials Registration Information: Randomised Comparison Between the STENTYS Self expanding Coronary Stent and a Balloon-expandable Stent in Acute Myocardial Infarction (APPOSITION II). ClinicalTrials.gov Identifier: NCT01008085 PMID- 26549375 TI - First-in-man transcatheter mitral valve-in-ring implantation with a repositionable and retrievable aortic valve prosthesis. AB - AIMS: Transcatheter interventions with balloon-expandable valves have been shown to be efficacious for the treatment of mitral annuloplasty failure but are limited by the fact that there is no opportunity for post-implantation adjustment. The aim of this study was to assess the safety and efficacy of the fully repositionable and retrievable Direct Flow Medical (DFM) valve for the treatment of mitral annuloplasty failure. METHODS AND RESULTS: Patients who underwent transcatheter mitral valve-in-ring (VIR) implantation of a DFM valve for failed mitral annuloplasty deemed high risk for redo surgery were included at four institutions. Eight patients underwent transcatheter mitral VIR procedures with implantation of the DFM valve. The DFM prosthesis was successfully positioned in all patients. Two patients required retrieval of the device due to a suboptimal result, and a further patient required repositioning of the valve with an ultimately successful implantation. During the 30-day follow-up period, two patients died for reasons unrelated to the valve implantation. The four patients with successful implantation had normal valve function associated with a significant improvement in their functional status. CONCLUSIONS: For the first time, we demonstrate the safety, efficacy and advantages of using the DFM prosthesis for the treatment of mitral annuloplasty failure. PMID- 26549376 TI - Natural vs. experimental hosts: The peculiar case of Taenia asiatica. PMID- 26549377 TI - Planar Dy3 + Dy3 clusters: design, structure and axial ligand perturbed magnetic dynamics. AB - Two unique Dy6 complexes with fascinating Dy3 + Dy3 structures were assembled, showing single-molecule magnetic behavior with high energy barriers of 116 and 181 K for Dy6-NO3 and Dy6-SCN. PMID- 26549378 TI - Functional characterization of recombinant human granulocyte colony stimulating factor (hGMCSF) immobilized onto silica nanoparticles. AB - OBJECTIVES: Granulocyte macrophage colony stimulating factor (GMCSF), an important therapeutic cytokine, was immobilized onto silica nanoparticles. Maintenance of structural integrity and biological performance in immobilized cytokine was assessed to augment its applicability in possible biomedical implications. RESULTS: Following its cloning and expression in E. coli, the recombinant human GMCSF (hGMCSF) was purified as a GST-tagged protein corresponding to a 42 kDa band on SDS-PAGE. The purified cytokine was immobilized onto biocompatible silica nanoparticles (~129.4 nm) by adsorption and the binding was confirmed by dynamic light scattering and infrared spectroscopy. Maximum binding of hGMCSF was at 6.4 ug mg(-1) silica nanoparticles. Efficient release of the cytokine from the nanoparticles with its structural integrity intact was deduced from circular dichroism spectroscopy. hGMCSF-immobilized silica nanoparticles efficiently increased the proliferation of RAW 264.7 macrophage cells with 50 % increase in proliferation at 600 ng hGMCSF ug(-1) silica nanoparticles. CONCLUSIONS: Silica nanoparticles successfully immobilized hGMCSF maintaining its structural integrity. The release of the immobilized cytokine from silica nanoparticles resulted in the increased proliferation of macrophages indicating the potential of the system in future applications. PMID- 26549379 TI - Caffeine intake in pregnancy: Relationship between internal intake and effect on birth weight. AB - We used a physiologically based kinetic model to simulate caffeine blood concentration-time profiles in non-pregnant and pregnant women. The model predicted concentration-time profile was in good accordance with experimental values. With 200 mg, the safe dose per occasion in non-pregnant women, AUC and peak concentration in pregnant women were nearly twice that of non-pregnant women. In order to derive a safe dose for the pregnant women we estimated the dose in the pregnant women model taken at once which would not exceed AUC and peak concentration in the non-pregnant women of 200 mg as single dose. The resulting dose is 100 mg caffeine per occasion which we recommend as safe. The caffeine dose of 200 mg per day is declared as safe for pregnant women with respect to the foetus by EFSA based on results on reduced birth weight in epidemiological studies. We modelled AUC and peak concentration for different caffeine doses to investigate the relationship between internal caffeine exposure and risk measures of reduced birth weight from epidemiological studies. The graphical analysis revealed that the reduction in birth weight was related to AUC and peak concentration up to a dose of 250 mg caffeine. PMID- 26549380 TI - Airway response to sirolimus therapy for the treatment of complex pediatric lymphatic malformations. AB - Head and neck lymphatic malformations can create airway management challenges requiring tracheotomy. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), may inhibit growth of lymphatic malformations. We describe two patients born with large lymphatic malformations with improved airway symptoms following sirolimus therapy. Patient #1 underwent tracheotomy and multi-modal therapy including sirolimus with reduction in airway involvement but regrowth after discontinuation of sirolimus. Patient #2 also experienced a significant response to sirolimus allowing for extubation and discharge without tracheotomy. Early initiation of sirolimus therapy should be considered as a means to avoid tracheotomy in complex head and neck lymphatic malformations. PMID- 26549381 TI - A 7666-bp genomic deletion is frequent in Chinese Han deaf patients with non syndromic enlarged vestibular aqueduct but without bi-allelic SLC26A4 mutations. AB - OBJECTIVES: To investigate the genetic cause of the patients with non-syndromic enlarged vestibular aqueduct (EVA) but without bi-allelic SLC26A4 mutations. METHODS: Presence of a homozygous genomic deletion was detected in a Chinese Han deaf patient (D1467-1) who failed to amplify the first three exons of SLC26A4. The breakpoints of the deletion were fine-mapped and revealed by PCR amplification and sequencing. This deletion was subsequently screened in 22 Chinese Han EVA probands with mono-allelic SLC26A4 mutations. The possible founder effect of the newly identified genomic deletion was evaluated by haplotype analysis. RESULTS: A homozygous c.-2071_307+3801del7666 deletion of SLC26A4 was identified in patient D1467-1. This novel genomic deletion was subsequently identified in 18% (4/22) of the Chinese Han EVA probands with mono allelic SLC26A4 mutations. Haplotype analysis showed that this genomic deletion is likely a founder mutation in Chinese Hans. CONCLUSION: Our results suggested that the cryptic c.-2071_307+3801del7666 deletion of SLC26A4 is relatively frequent in Chinese Han non-syndromic EVA patients without bi-allelic SLC26A4 mutations. Screening of this genomic deletion should be incorporated into the routine DNA testing of SLC26A4 in Chinese Hans. PMID- 26549382 TI - Combination of cytokine-induced killer and dendritic cells pulsed with antigenic alpha-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy. AB - BACKGROUND AIMS: Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients. METHODS: Fourteen refractory lymphoma patients (age, 29-74 y) were enrolled in the trial. alpha-1,3-galactosyl (alpha-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant alpha-1,3-galactosyltransferase (alpha-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti-alpha-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donor lymphoma patients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment. RESULTS: Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and beta2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-gamma expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment. CONCLUSIONS: Lymphoma cell-specific alpha-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma. PMID- 26549383 TI - Evaluation of a cell-banking strategy for the production of clinical grade mesenchymal stromal cells from Wharton's jelly. AB - BACKGROUND AIMS: Umbilical cord (UC) has been proposed as a source of mesenchymal stromal cells (MSCs) for use in experimental cell-based therapies provided that its collection does not raise any risk to the donor, and, similar to bone marrow and lipoaspirates, UC-MSCs are multipotent cells with immuno-modulative properties. However, some of the challenges that make a broader use of UC-MSCs difficult include the limited availability of fresh starting tissue, time consuming processing for successful derivation of cell lines, and the lack of information on identity, potency and genetic stability in extensively expanded UC MSCs, which are necessary for banking relevant cell numbers for preclinical and clinical studies. METHODS: Factors affecting the success of the derivation process (namely, time elapsed from birth to processing and weight of fragments), and methods for establishing a two-tiered system of Master Cell Bank and Working Cell Bank of UC-MSCs were analyzed. RESULTS: Efficient derivation of UC-MSCs was achieved by using UC fragments larger than 7 g that were processed within 80 h from birth. Cells maintained their immunophenotype (being highly positive for CD105, CD90 and CD73 markers), multi-potentiality and immuno-modulative properties beyond 40 cumulative population doublings. No genetic abnormalities were found, as determined by G-banding karyotype, human telomerase reverse transcriptase activity was undetectable and no toxicity was observed in vivo after intravenous administration of UC-MSCs in athymic rats. DISCUSSION: This works demonstrates the feasibility of the derivation and large-scale expansion of UC-MSCs from small and relatively old fragments of UC typically discarded from public cord blood banking programs. PMID- 26549384 TI - Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. AB - BACKGROUND AIMS: This study developed a new method to expand CD3(-)CD56(+) natural killer (NK) cells from human peripheral blood mononuclear cells (PBMCs) without feeder cells for clinical trials. METHODS: PBMCs from healthy subjects were co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies and cultured for 14 days in newly developed NKGM-1 medium containing autologous plasma and interleukin-2. Expanded NK cells were examined for cell number, phenotype, in vitro and in vivo cytotoxicity and interferon (IFN)-gamma secretion. We also evaluated the proliferative ability of NK cells after cryopreservation. A patient with advanced pancreatic cancer was treated with autologous-expanded NK cells through the use of this method in combination with chemotherapy. RESULTS: Expanded NK cells expressed higher levels of activating molecules compared with resting NK cells and exhibited potent cytotoxicity against K562 cells and IFN gamma secretion by cytokine stimulation. Significant anti-tumor activity was observed in immunodeficient mice injected with the human pancreatic cancer cell line BxPC-3. Large-scale cultures generated a median 5.7 * 10(9) NK cells from 20 mL of peripheral blood (n = 38) after 14 days of culture and 8.4 * 10(9) NK cells after 18 days of culture through the use of a cryopreservation procedure. The number of NK cells and cytotoxic activity in the peripheral blood of the patient with pancreatic cancer greatly increased, and successful clinical responses were observed after multiple infusions of expanded NK cells. CONCLUSIONS: These data demonstrate that this simple and safe methodology for the ex vivo expansion of NK cells can be used for cancer immunotherapy. PMID- 26549385 TI - Debating LGBT Workplace Protections in the Bible Belt: Social Identities in Legislative and Media Discourse. AB - This article reports a case study of the legislative and media discourse surrounding the addition of sexual orientation and gender identity language to the employment nondiscrimination ordinance of a city in the heart of the Bible Belt. The purpose of the study is to uncover how different identities were constructed and contested at city council meetings and in the news media on the way to passing legal protection for LGBT city employees in a region that is often characterized by anti-gay prejudice. This debate over the nondiscrimination ordinance centered on the question of whether LGBT identities are equivalent to identity categories based on race, gender, or religious belief, and it was shaped by various intergroup communication dynamics, specifically between members of the LGBT minority and the straight majority, between LGBT and Christian identities, and between "true" and "false" Christian identities. PMID- 26549386 TI - A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome. AB - The most common cause of chronic oro-facial pain is a group of disorders collectively termed temporomandibular disorders (TMDs). Chronic painful TMD is thought to be a 'central sensitivity syndrome' related to hypersensitivity of the nervous system, but the cause is unknown. A similar understanding is proposed for other unexplained conditions, including chronic fatigue syndrome (CFS). Exploring the comorbidity of the two conditions is a valuable first step in identifying potential common aetiological mechanisms or treatment targets. METHOD: Systematic literature review. Studies were included if they recruited community or control samples and identified how many reported having both TMD and CFS, or if they recruited a sample of patients with either TMD or CFS and measured the presence of the other condition. RESULTS: Six papers met inclusion criteria. In studies of patients with CFS (n = 3), 21-32% reported having TMD. In a sample of people with CFS and fibromyalgia, 50% reported having TMD. Studies in people with TMD (n = 3) reported 0-43% having CFS. Studies in samples recruited from oro-facial pain clinics (n = 2) reported a lower comorbidity with CFS (0-10%) than a study that recruited individuals from a TMD self-help organisation (43%). CONCLUSION: The review highlights the limited standard of evidence addressing the comorbidity between oro-facial pain and CFS. There is a valuable signal that the potential overlap in these two conditions could be high; however, studies employing more rigorous methodology including standardised clinical assessments rather than self report of prior diagnosis are needed. PMID- 26549387 TI - Recreational Anabolic-Androgenic Steroid Use Associated With Liver Injuries Among Brazilian Young Men. AB - BACKGROUND: The recreational use of anabolic-androgenic steroids (AAS) has reached alarming levels among healthy people. However, several complications have been related to consumption of these drugs, including liver disorders. OBJECTIVE: To evaluate the prevalence of liver injuries in young Brazilian recreational AAS users. METHODS: Between February/2007 and May/2012 asymptomatic bodybuilders who were >=18 years old and reported AAS use for >=6 months were enrolled. All had clinical evaluations, abdominal ultrasound (AUS), and blood tests. RESULTS: 182 individuals were included in the study. The median age (interquartile range) was 26.0 years (22.0-30.0) and all were male. Elevated liver enzyme levels were observed in 38.5% (n = 70) of AAS users, and creatine phosphokinase was normal in 27.1% (n = 19) of them. Hepatic steatosis was observed by AUS in 12.1% of the sample. One individual had focal nodular hyperplasia and another had hepatocellular adenoma. One case each of hepatitis B and C virus infection was found. A diagnosis of toxic liver injury was suggested in 23 (12.6%) AAS users without a history of alcohol or other medications/drugs consumption, or evidence of other liver diseases. CONCLUSIONS/IMPORTANCE: Young Brazilian recreational AAS users presented a wide spectrum of liver injuries that included hepatotoxicity, fatty liver, and liver neoplasm. They also presented risk factors for liver diseases such as alcohol consumption and hepatitis B and C virus infection. The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries. PMID- 26549388 TI - Difficulty interpreting the results of some trials: the case of therapeutic hypothermia after pediatric cardiac arrest. PMID- 26549389 TI - Clinical Outcome After Permanent Pacemaker Implantation in Patients With a High Percentage of Ventricular Pacing. AB - Previous reports have suggested that right ventricular apical pacing may lead to cardiac dysfunction. Septal pacing is thought to be superior to apical pacing in the prevention of cardiac dyssynchrony, however, there have been no reports on the contribution of septal pacing to improving clinical outcome.We retrospectively evaluated factors associated with cardiac events in patients with right ventricular pacing.The study population consisted of 256 consecutive patients newly implanted with permanent pacemakers and followed-up for 29 +/- 18 months. Cardiac events, consisting of cardiac death or heart failure requiring hospitalization, occurred in 22 patients. Kaplan-Meier curves revealed that patients with a high percentage of ventricular pacing (> 90%, n = 101, group H) had a higher incidence of cardiac events than patients with a low percentage of ventricular pacing (< 10%, n = 83, group L) (P = 0.002). In group H, multivariate analysis showed that age (HR: 1.174, 95%CI: 1.066-1.291, P = 0.001), ejection fraction (EF) (HR: 0.898, 95%CI: 0.836-0.964, P = 0.003), QRS duration during cardiac pacing (HR: 1.059, 95%CI: 1.017-1.103, P = 0.006), and existing basal cardiac diseases (HR: 13.080, 95%CI: 2.463-69.479, P = 0.003) were significant predictors of cardiac events, although pacing site had no significant association with prognosis (P = 0.56).Higher age, lower EF, longer QRS duration during cardiac pacing, and existing basal cardiac diseases are associated with poor prognosis in patients with a high percentage of ventricular pacing. PMID- 26549390 TI - Correlation Between Arteriosclerosis and Periodontal Condition Assessed by Lactoferrin and alpha1-Antitrypsin Levels in Gingival Crevicular Fluid. AB - Patients with periodontal disease exhibit exacerbated atherosclerosis, aortic stiffness, or vascular endothelial dysfunction. However, in a recent scientific statement, the American Heart Association noted that neither has periodontal disease been proven to cause atherosclerotic vascular disease nor has the treatment of periodontal disease been proven to prevent atherosclerotic vascular disease. Therefore, the aim of the present study was to examine the correlation between periodontal condition and arteriosclerosis in patients with coronary artery disease (CAD), which is usually accompanied by systemic arteriosclerosis.We measured levels of gingival crevicular fluid lactoferrin (GCF Lf) and alpha1-antitrypsin (GCF-AT) in 72 patients (67 +/- 8 years, 56 men) with CAD. Furthermore, we evaluated the maximum intima-media thickness (max IMT) and plaque score of the carotid arteries as well as brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) of the brachial artery, each of which is a parameter for determining arteriosclerosis status. The average level of GCF-Lf was 0.29 +/- 0.36 ug/mL and that of GCF-AT was 0.31 +/- 0.66 ug/mL, with significant correlation between the two (r = 0.701, P < 0.001). No significant difference in GCF-Lf and GCF-AT levels was observed between patients with single-, double-, and triple-vessel CAD. There were no significant correlations between the arteriosclerosis parameters (ie, max IMT, plaque score, baPWV, and FMD) and GCF-Lf or GCF-AT.No correlation between the GCF biomarkers and the severity of arteriosclerosis was detected. This result may suggest that worsening of the periodontal condition assessed by GCF biomarkers is not a major potential risk factor for arteriosclerosis. PMID- 26549391 TI - Next Generation ARBs. Going Beyond Modulation of the Renin-Angiotensin System. PMID- 26549392 TI - Mid-Term Administration of Tolvaptan Improves Renal Function Accompanied by Dose Reduction in Furosemide in Aquaporin-Defined Responders. PMID- 26549393 TI - Physical Activity. A Useful Marker for Cardiac Rehabilitation? PMID- 26549394 TI - Work-Related Psychosocial Hazards and Arteriosclerosis. AB - The association of psychosocial stress with cardiovascular disease (CVD) is still inconclusive. The aim of this study was to examine the relationships between arteriosclerosis and various work-related conditions among medical employees with various job titles.A total of 576 medical employees of a regional hospital in Taiwan with a mean age of 43 years and female gender dominance (85%) were enrolled. Arteriosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV). Workrelated conditions included job demands, job control, social support, shift work, work hours, sleep duration, and mental health. The crude relationship between each of the selected covariates and baPWV was indicated by Spearman correlation coefficients. A multiple linear regression model was further employed to estimate the adjusted associations of selected covariates with arteriosclerosis.The mean baPWV of participants was 11.4 +/- 2.2 m/s, with the value for males being significantly higher than that for females. The baPWV was associated with gender, age, medical profession, work hours, work type, depression, body mass index, systolic and diastolic blood pressures, fasting glucose, and cholesterol. After being fully adjusted by these factors, only sleep duration of less than 6 hours and weekly work hours longer than 60 hours were significantly associated with increased risk of arteriosclerosis. The conditions of job demands, job control, social support, shift work, and depression showed no significant association with baPWV.Longer work hours and shorter sleep durations were associated with an increased risk of arteriosclerosis. These findings should make it easier for the employer or government to stipulate rational work hours in order to avoid the development of cardiovascular disease among their employees. PMID- 26549395 TI - Effects of Phase II Comprehensive Cardiac Rehabilitation on Coronary Plaque Volume After Acute Coronary Syndrome. AB - The present study aimed to determine the effects of phase II (PII) comprehensive cardiac rehabilitation (CR) on coronary plaque volume in patients after acute coronary syndrome (ACS).We assigned 46 patients with ACS who had undergone standard phase I CR into groups who proceeded with PII-CR (PII-CR; n = 21) and those who did not (non-PII-CR; n = 25). We then measured anthropometric parameters and daily physical activity using a pedometer for up to 60 days. The isokinetic strength of the knee extensor and flexor muscles and exercise tolerance were tested and non-culprit lesions were analyzed using volumetric intravascular ultrasound at baseline and 6 months later.Baseline characteristics did not significantly differ between the two groups and exercise tolerance was significantly improved in both. Waist size and fat weight were significantly decreased, and muscle strength was significantly increased in the PII-CR group but not in the non-PII-CR group. The percent change in plaque volume (primary endpoint) did not differ significantly between the two groups. The percent change in plaque volume was significantly and negatively correlated with daily physical activity.Although risk factors, muscle strength, and exercise tolerance were improved by PII-CR, plaque regression did not differ significantly between the two study groups. A significant correlation between percent change in coronary plaque volume and physical activity was observed. A comprehensive phase II-CR, including frequent supervised exercise sessions and a program encouraging an increase in daily physical activity, may reduce plaque volume in patients after ACS (UMIN000006038). PMID- 26549396 TI - A Case of Adult-Onset Acute Rheumatic Fever With Long-Lasting Atrioventricular Block Requiring Permanent Pacemaker Implantation. AB - A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin O levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However, she had syncope due to complete atrioventricular block with asystole longer than 10 seconds. Consequently, we implanted a permanent pacemaker. Although we prescribed prednisolone, the efficacy of which was limited for the patient's conduction disturbance, the complete atrioventricular block persisted. In our systematic review of 12 similar cases, the duration of complete heart block was always transient and there was no case requiring a permanent pacemaker. We thus encountered a very rare case of adult-onset acute rheumatic fever with persistent complete atrioventricular block necessitating permanent pacemaker implantation. PMID- 26549397 TI - Diverse Findings in Calcified Thrombus Between Histopathology and In Vivo Imaging Including Intravascular Ultrasound, Optical Coherence Tomography, and Angioscopy. AB - A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy. PMID- 26549398 TI - Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease. AB - Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 +/- 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG >= 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD. PMID- 26549399 TI - Effect of a Low-Intensity Pulsed Ultrasound Device, SX-1001, on Clinical Symptoms in Buerger Disease With Limb Ischemia. AB - Buerger disease is a rare disease of unknown etiology and cannot be treated by bypass surgery or percutaneous re-endovascularization. Although the need for effective limb ischemia prevention strategies is increasingly being recognized, effective preventative strategies are insufficient. The aim of this study using a new pulsed ultrasound device, SX-1001, is to determine whether treatment using SX 1001 can mitigate rest pain and improve blood supply to ischemic legs in patients with Buerger disease. This study is a multicenter, double-blinded, parallel randomized clinical trial testing the efficacy and safety of SX-1001. Treatment using SX-1001 is expected to result in reduction of the visual analog scale score for pain in Buerger disease patients who have Fontaine stage III. A total of 44 patients from 20 hospitals in Japan will be enrolled. The primary endpoint of the trial is a change in rest pain intensity on the visual analog scale score from baseline to 24 weeks. This trial will be the first to show the safety and efficacy of low-intensity pulsed ultrasound using SX-1001 for clinical symptoms in patients with Buerger disease. Low-intensity pulsed ultrasound may be a new therapy for limb ischemia. Ethical approval has been obtained from each of the participating institutes. Study findings will be disseminated through peer reviewed journals and at scientific conferences.This study is registered at UMIN Clinical Trial Registry (UMIN000014757). PMID- 26549400 TI - The natural compound codonolactone attenuates TGF-beta1-mediated epithelial-to mesenchymal transition and motility of breast cancer cells. AB - Codonolactone (CLT), a natural product, is the major bioactive component of Atractylodes lancea, and also found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes macrocephala Koidz. This sesquiterpene lactone has been demonstrated to exhibit a range of activities, including anti-allergic activity, anti-inflammatory, anticancer, gastroprotective and neuroprotective activity. Previously, we found that CLT showed significant anti-metastatic properties in vitro and in vivo. In order to determine whether EMT-involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-EMT properties of CLT and its potential mechanisms. Here it was demonstrated that CLT inhibited TGF-beta1-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, downregulation of TGF-beta signaling was associated with the anti-EMT properties of CLT. Data from western blotting showed that, in breast cancer cells, TGF-beta1 stimulated the activation of Runx2, and CLT blocked the activation of Runx2. Finally, to verify whether CLT-induced EMT inhibition leads to suppression of metastatic potential, the effects of CLT on cell invasion and migration were determined. It was found that TGF-beta1-induced migration and invasion was significantly blocked by CLT in both MDA-MB-231 and MDA-MB-468 cells. Collectively, our findings demonstrated that CLT inhibited programming of EMT in vitro and in vivo, resulting in inhibition of motility of metastatic breast cancer cells. The inhibitory effect of CLT was due to its ability to inhibit TGF beta signaling and Runx2 phosphorylation. PMID- 26549402 TI - Esomeprazole and rabeprazole did not reduce antiplatelet effects of aspirin/clopidogrel dual therapy in patients undergoing percutaneous coronary intervention: a prospective, randomized, case-control study. AB - OBJECTIVES: Controversy has been prompted based on drug interaction between proton pump inhibitors (PPIs) and aspirin/clopidogrel leading to weakened effects. However, whether such interaction was drug-specific or class effect remains controversial. This study predicted the impact of esomeprazole and rabeprazole on efficacy of dual antiplatelet therapy (DAPT). METHODS: This study, involving 150 patients, evaluated the efficacy of DAPT upon concomitant use of esomeprazole (40 mg/d) or rabeprazole (20 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at day 1, day 3 and day 30 end points after initiation of DAPT. RESULTS: No significance were observed by post-hoc analysis of treatment-by-period interaction in LTA value and VASP-PRI value when compared with non-PPI users, which suggests no carryover effect in both PPIs over the 30-day treatment period. Moreover, no statistical differences was in LTA or VASP-PRI value in esomeprazole group while rabeprazole group showed decreased in antiplatelet function of DAPT at the day 3 and day 30 end points. CONCLUSION: Although antiplatelet effect of DAPT were not affected upon concomitant use of both PPIs over the 30-day treatment period, esomeprazole exerts much more stable impact on antiplatelet effect than rabeprazole among respective end points. PMID- 26549403 TI - Multilayered dense collagen-silk fibroin hybrid: a platform for mesenchymal stem cell differentiation towards chondrogenic and osteogenic lineages. AB - Type I collagen is a major structural and functional protein in connective tissues. However, collagen gels exhibit unstable geometrical properties, arising from extensive cell-mediated contraction. In an effort to stabilize collagen based hydrogels, plastic compression was used to hybridize dense collagen (DC) with electrospun silk fibroin (SF) mats, generating multilayered DC-SF-DC constructs. Seeded mesenchymal stem cell (MSC)-mediated DC-SF-DC contraction, as well as growth and differentiation under chondrogenic and osteogenic supplements, were compared to those seeded in DC and on SF alone. The incorporation of SF within DC prevented extensive cell-mediated collagen gel contraction. The effect of the multilayered hybrid on MSC remodelling capacity was also evident at the transcription level, where the expression of matrix metalloproteinases and their inhibitor (MMP1, MMP2, MMP3, MMP13 and Timp1) by MSCs within DC-SF-DC were comparable to those on SF and significantly downregulated in comparison to DC, except for Timp1. Chondrogenic supplements stimulated extracellular matrix production within the construct, stabilizing its multilayered structure and promoting MSC chondrogenic differentiation, as indicated by the upregulation of the genes Col2a1 and Agg and the production of collagen type II. In osteogenic medium there was an upregulation in ALP and OP along with the presence of an apatitic phase, indicating MSC osteoblastic differentiation and matrix mineralization. In sum, these results have implications on the modulation of three-dimensional collagen-based gel structural stability and on the stimulation and maintenance of the MSC committed phenotype inherent to the in vitro formation of chondral tissue and bone, as well as on potential multilayered complex tissues. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549401 TI - A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study. AB - In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID- 26549404 TI - Therapist activities preceding setbacks in the assimilation process. AB - OBJECTIVE: This study examined the therapist activities immediately preceding assimilation setbacks in the treatment of a good-outcome client treated with linguistic therapy of evaluation (LTE). METHOD: Setbacks (N = 105) were defined as decreases of one or more assimilation stages from one passage to the next dealing with the same theme. The therapist activities immediately preceding those setbacks were classified using two kinds of codes: (a) therapist interventions and (b) positions the therapist took toward the client's internal voices. RESULTS: Preceding setbacks to early assimilation stages, where the problem was unformulated, the therapist was more often actively listening, and the setbacks were more often attributable to pushing a theme beyond the client's working zone. Preceding setbacks to later assimilation stages, where the problem was at least formulated, the therapist was more likely to be directing clients to consider alternatives, following the LTE agenda, and setbacks were more often attributable to the client following these directives shifting attention to less assimilated (but nevertheless formulated) aspects of the problem. CONCLUSIONS: At least in this case, setbacks followed systematically different therapist activities depending on the problem's stage of assimilation. Possible implications for the assimilation model's account of setbacks and for practice are discussed. PMID- 26549405 TI - A review of manual wheelchairs. AB - PURPOSE: To review the scientific literature published in the last 14 years on the different types of manual wheelchairs. METHOD: A systematic review of the literature was conducted to find the recent research on manual wheelchairs. RESULTS: The findings of 77 references on pushrim-propelled wheelchairs, crank propelled wheelchairs, lever-propelled wheelchairs, geared manual wheelchairs and pushrim-activated power-assist wheelchairs are reported. CONCLUSION: The pushrim propelled wheelchair is light, easy to steer and has good indoor manoeuvrability but is very inefficient and causes serious upper body overloading so that long term use leads to steadily deteriorating capability for the user and ultimately a transition to a powered chair. Whilst the latter is less physically demanding, the sedentary lifestyle and decreasing muscle use lead to several secondary health problems. Crank- and lever-propelled wheelchairs and geared pushrim wheelchairs are more efficient and less demanding and may improve the quality of life of the user by expanding the range of accessible environments, reducing upper body pain, increasing independence and avoiding or delaying the 'debilitating cycle'. However, wheelchairs with these alternative modes of propulsion are often heavier, wider and/or longer and are less easy to steer, brake and fold than the pushrim wheelchair. Implications for rehabilitation Pushrim-propelled wheelchairs are difficult to drive on outdoor paths (grass and gravel/sand surfaces) and ramps so that users are confined to restricted environments and have limited participation in everyday activities. The repetitive strain imposed on the upper body by pushrim propulsion leads to very high prevalence of shoulder and wrist pain in manual wheelchair users. Crank propelled and lever-propelled wheelchairs are more efficient and less straining than pushrim propelled wheelchairs, allowing users to access more challenging environments, prolong independence and improve the quality of life. PMID- 26549407 TI - Quality of life and mental health among women with ovarian cancer: examining the role of emotional and instrumental social support seeking. AB - The purpose of the present study was to examine the role of emotional and instrumental social support seeking in the quality of life (QOL) and mental health of women with ovarian cancer. Participants were recruited through the Pennsylvania Cancer Registry, and one hundred women took part in a mail questionnaire that collected information on their demographics, medical status, social support seeking, QOL and mental health including anxiety, depression and stress. Hierarchical linear regression analyses were conducted to assess the influence of emotional and instrumental social support seeking on QOL and mental health. After controlling for remission status, greater emotional social support seeking was predictive of higher overall QOL, social/family QOL, functional QOL and lower depression scores. Instrumental social support seeking was not significant in the models. The results illustrate that social support seeking as a coping mechanism is an important consideration in the QOL and mental health of women with ovarian cancer. Future studies should examine the psychological and behavioral mediators of the relationship to further understand the QOL and mental health of women with ovarian cancer. PMID- 26549406 TI - Impact of Visual Impairment and Eye diseases on Mortality: the Singapore Malay Eye Study (SiMES). AB - We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40-80 years between 2004-2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25-1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24-2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all cause (HR 1.70; 95% CI, 1.25-2.36) and CVD mortality (HR 1.57; 95% CI, 1.05 2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26-7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality. PMID- 26549408 TI - Exploring the interaction between human focal adhesion kinase and inhibitors: a molecular dynamic simulation and free energy calculations. AB - Focal adhesion kinase is an important target for the treatment of many kinds of cancers. Inhibitors of FAK are proposed to be the anticancer agents for multiple tumors. The interaction characteristic between FAK and its inhibitors is crucial to develop new inhibitors. In the present article, we used Molecular Dynamic (MD) simulation method to explore the characteristic of interaction between FAK and three inhibitors (PHM16, TAE226, and ligand3). The MD simulation results together with MM-GB/SA calculations show that the combinations are enthalpy-driven process. Cys502 and Asp564 are both essential residues due to the hydrogen bond interactions with inhibitors, which was in good agreement with experimental data. Glu500 can form a non-classical hydrogen bond with each inhibitor. Arg426 can form electrostatic interactions with PHM16 and ligand3, while weaker with TAE226. The electronic static potential was employed, and we found that the ortho position methoxy of TAE226 has a weaker negative charge than the meta-position one in PHM16 or ligand3. Ile428, Val436, Ala452, Val484, Leu501, Glu505, Glu506, Leu553, Gly563 Leu567, Ser568 are all crucial residues in hydrophobic interactions. The key residues in this work will be available for further inhibitor design of FAK and also give assistance to further research of cancer. PMID- 26549409 TI - Quantum Metrology: Surpassing the shot-noise limit with Dzyaloshinskii-Moriya interaction. AB - Entanglement is at the heart of quantum technologies such as quantum information and quantum metrology. Providing larger quantum Fisher information (QFI), entangled systems can be better resources than separable systems in quantum metrology. However the effects on the entanglement dynamics such as decoherence usually decrease the QFI considerably. On the other hand, Dzyaloshinskii-Moriya (DM) interaction has been shown to excite entanglement. Since an increase in entanglement does not imply an increase in QFI, and also there are cases where QFI decreases as entanglement increases, it is interesting to study the influence of DM interaction on quantum metrology. In this work, we study the QFI of thermal entanglement of two-qubit and three-qubit Heisenberg models with respect to SU(2) rotations. We show that even at high temperatures, DM interaction excites QFI of both ferromagnetic and antiferromagnetic models. We also show that QFI of the ferromagnetic model of two qubits can surpass the shot-noise limit of the separable states, while QFI of the antiferromagnetic model in consideration can only approach to the shot-noise limit. Our results open new insights in quantum metrology with Heisenberg models. PMID- 26549410 TI - An analysis of caregiver burden of patients with hemodialysis and peritoneal dialysis. AB - Since caregivers have roles and responsibilities in all phases from the diagnosis of the disease to discharge and homecare, their care burdens increase. The problems experienced by caregivers, whose care burden increase and accordingly whose life quality is deteriorated, complicate the treatment-receiving patient's adaptation to the disease. This study was performed to determine the burden to primary caregivers of patients undergoing dialysis. This descriptive study was conducted with the family caregivers of 114 patients from Erzurum Ataturk University's Medical Faculty Nephrology Department: 54 were relatives of patients receiving hemodialysis and 60 were relatives of patients receiving peritoneal dialysis during August to December 2014. The percentage of the patients with low levels of caregiver burden is 13% in the hemodialysis group, while it is 35% in the peritoneal dialysis group. These findings are statistically significant. To conclude, chronic diseases affect not only patients, but also their relatives who care for them. Nursing care needs to include both patients and their relatives and support them. It is hoped that this study will guide nursing care in this direction. PMID- 26549412 TI - Chronic critical illness: the price of survival. AB - BACKGROUND: The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients. MATERIALS & METHODS: No absolute definition of the disease is currently available, although most patients are characterized by the need for prolonged mechanical ventilation. Mortality rates are still high even after dismissal from intensive care unit (ICU) and transfer to specialized rehabilitation care settings. RESULTS: In recent years, some studies have tried to clarify the pathophysiological characteristics underlying chronic critical illness (CCI), a disease that is also characterized by severe endocrine and inflammatory impairments, partly accounting for the almost constant set of symptoms. DISCUSSION: Currently, no specific treatment is available. However, a strategic early therapeutic approach on ICU admission might try to prevent the progress of the acute disease towards chronic critical illness. PMID- 26549411 TI - Mechanisms for the Generation of Two Quadruplications Associated with Split-Hand Malformation. AB - Germline copy-number variants (CNVs) involving quadruplications are rare and the mechanisms generating them are largely unknown. Previously, we reported a 20-week gestation fetus with split-hand malformation; clinical microarray detected two maternally inherited triplications separated by a copy-number neutral region at 17p13.3, involving BHLHA9 and part of YWHAE. Here, we describe an 18-month-old male sibling of the previously described fetus with split-hand malformation. Custom high-density microarray and digital droplet PCR revealed the copy-number gains were actually quadruplications in the mother, the fetus, and her later born son. This quadruplication-normal-quadruplication pattern was shown to be expanded from the triplication-normal-triplication CNV at the same loci in the maternal grandmother. We mapped two breakpoint junctions and demonstrated that both are mediated by Alu repetitive elements and identical in these four individuals. We propose a three-step process combining Alu-mediated replicative-repair-based mechanism(s) and intergenerational, intrachromosomal nonallelic homologous recombination to generate the quadruplications in this family. PMID- 26549414 TI - Global health and nursing and midwifery leadership. PMID- 26549413 TI - Role of genetic mutations in folate-related enzyme genes on Male Infertility. AB - Several studies showed that the genetic mutations in the folate-related enzyme genes might be associated with male infertility; however, the results were still inconsistent. We performed a meta-analysis with trial sequential analysis to investigate the associations between the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G mutations and the MTHFR haplotype with the risk of male infertility. Overall, a total of 37 studies were selected. Our meta-analysis showed that the MTHFR C677T mutation was a risk factor for male infertility in both azoospermia and oligoasthenoteratozoospermia patients, especially in Asian population. Men carrying the MTHFR TC haplotype were most liable to suffer infertility while those with CC haplotype had lowest risk. On the other hand, the MTHFR A1298C mutation was not related to male infertility. MTR A2756G and MTRR A66G were potential candidates in the pathogenesis of male infertility, but more case control studies were required to avoid false-positive outcomes. All of these results were confirmed by the trial sequential analysis. Finally, our meta analysis with trial sequential analysis proved that the genetic mutations in the folate-related enzyme genes played a significant role in male infertility. PMID- 26549415 TI - Isolation of culturable mycobiota from agricultural soils and determination of tolerance to glyphosate of nontoxigenic Aspergillus section Flavi strains. AB - Glyphosate-based herbicides are extensively used in Argentina's agricultural system to control undesirable weeds. This study was conducted to evaluate the culturable mycobiota [colony forming units (CFU) g(-1) and frequency of fungal genera or species] from an agricultural field exposed to pesticides. In addition, we evaluated the tolerance of A. oryzae and nontoxigenic A. flavus strains to high concentrations (100 to 500 mM - 17,000 to 84,500 ppm) of a glyphosate commercial formulation. The analysis of the mycobiota showed that the frequency of the main fungal genera varied according to the analyzed sampling period. Aspergillus spp. or Aspergillus section Flavi strains were isolated from 20 to 100% of the soil samples. Sterilia spp. were also observed throughout the sampling (50 to 100%). Aspergillus section Flavi tolerance assays showed that all of the tested strains were able to develop at the highest glyphosate concentration tested regardless of the water availability conditions. In general, significant reductions in growth rates were observed with increasing concentrations of the herbicide. However, a complete inhibition of fungal growth was not observed with the concentrations assayed. This study contributes to the knowledge of culturable mycobiota from agricultural soils exposed to pesticides and provides evidence on the effective growth ability of A. oryzae and nontoxigenic A. flavus strains exposed to high glyphosate concentrations in vitro. PMID- 26549416 TI - Environmental influences on living marine stromatolites: insights from benthic microalgal communities. AB - Extant marine stromatolites act as partial analogues of their Achaean counterparts, but are rare due to depleted ocean calcium carbonate levels and suppression by eukaryotic organisms. Unique, peritidal tufa stromatolites at the interface between marine and freshwater inputs were discovered in South Africa in the past decade. Our aim was to investigate the benthic microalgal community (green algae, diatoms and cyanobacteria) of these stromatolites to assess succession and dominance patterns using real-time, in situ measurements of algal concentrations and composition. These biological measurements were modelled using generalized linear modelling (GLM) multivariate statistics against water physical and chemical parameters measured at regular monthly intervals, from January to December 2014. Salinity peaked and temperature dipped in winter, with both correlated to microalgal community change (GLM: P < 0.01). Diatoms and cyanobacteria, which construct the stromatolites, were consistently the dominant groups within the algal community, with minimal green algae present throughout the year. Importantly, this demonstrates a unique, relatively stable microalgal stromatolite community as opposed to those of other marine stromatolites, which likely require seasonal and stochastic disturbance to persist. This has implications in terms of interpreting community succession and differential layering in modern and fossilized stromatolites respectively. PMID- 26549417 TI - Harmine Hydrochloride Triggers G2 Phase Arrest and Apoptosis in MGC-803 Cells and SMMC-7721 Cells by Upregulating p21, Activating Caspase-8/Bid, and Downregulating ERK/Bad Pathway. AB - This study aimed to investigate the effects of harmine hydrochloride (HMH) on digestive tumor cells in vitro and its molecular mechanism. MTT assays showed that HMH inhibited the proliferation of some human cancer cell lines and had no obvious inhibitory effects on human LO2 cells. Flow cytometry assays showed that HMH trigged G2 phase arrest in MGC-803 cells and SMMC-7721 cells, while the expression of cyclin A, cyclin B, p21, Myt1, and p-cdc2 (Tyr15) was upregulated. Flow cytometry assays also showed that the percentages of apoptotic cells were increased, the mitochondrial transmembrane potential (DeltaPsim) decreased, and the cleavage of caspase-9, caspase-3, and poly (Adenosine diphosphate ribose) polymerase (PARP) were observed, the expression of Bad increased, phospho-Bad (S112) decreased, pro-caspase-8 was cleaved, and Bid (22 kDa) was cleaved. The expression of p-ERK decreased in both cells. In conclusion, these results demonstrated that HMH upregulates the expression of p21, activates Myt1 and inhibits cdc2 by phospho-cdc2 (Y15), and triggers G2 phase arrest in both MGC-803 cells and SMMC-7721 cells. It can also activate the mitochondria-related cell apoptosis pathway through the caspase-8/Bid pathway, inhibiting the ERK/Bad pathway and promoting apoptosis in both of these two cell types. PMID- 26549418 TI - Hemicelluloses/montmorillonite hybrid films with improved mechanical and barrier properties. AB - A facile and environmentally friendly method was introduced to incorporate montmorillonite (MMT) as an inorganic phase into quaternized hemicelluloses (QH) for forming hemicellulose-based films. Two fillers, polyvinyl alcohol (PVA) and chitin nanowhiskers (NCH), were added into the hemicelluloses/MMT hybrid matrices to prepare hybrid films, respectively. The hybrid films were nanocomposites with nacre-like structure and multifunctional characteristics including higher strength and good oxygen barrier properties via the electrostatic and hydrogen bonding interactions. The addition of PVA and NCH could induce changes in surface topography, and effectively enhance mechanical strength, thermal stability, transparency, and oxygen barrier properties. The tensile strengths of the composite films FPVA(0.3), FPVA(0.5), and FNCH(0.8) were 53.7, 46.3, and 50.1 MPa, respectively, which were 171%, 134%, and 153% larger than the FQH-MMT film (19.8 MPa). The tensile strength, and oxygen transmission rate of QH-MMT-PVA film were better than those of quaternized hemicelluloses/MMT films. Thus, the proper filler is very important for the strength of the hybrid film. These results provide insights into the understanding of the structural relationships of hemicellulose-based composite films in coating and packaging application for the future. PMID- 26549419 TI - Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients. AB - We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value < 0.05) between the ovarian cancer and healthy control. According to the receiver operating characteristic curve analysis, arabitol was the most potentially specific biomarker for discriminating ovarian cancer from healthy control, having an area under the curve of 0.911. A panel of metabolite markers composed of maltose, maltotriose, raffinose, and mannitol was selected, which was able to discriminate the ovarian cancer from the benign ovarian tumor counterparts, with an area under concentration-time curve value of 0.832. Endogenous carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. PMID- 26549420 TI - Upregulation of p-Akt by glial cell line-derived neurotrophic factor ameliorates cell apoptosis in the hippocampus of rats with streptozotocin-induced diabetic encephalopathy. AB - The loss of neurotrophic factor support has been shown to contribute to the development of the central nervous system. Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, is closely associated with apoptosis and exerts neuroprotective effects on numerous populations of cells. However, the underlying mechanisms of these protective effects remain unknown. In the present study, a significant increase in Bax levels and DNA fragmentation was observed in the hippocampus obtained from the brains of diabetic rats 60 days after diabetes had been induced. The apoptotic changes were correlated with the loss of GDNF/Akt signaling. GDNF administration was found to reverse the diabetes-induced Bax and DNA fragmentation changes. This was associated with an improvement in the level of p-Akt/Akt. In addition, combination of GDNF with a specific inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway, Wortmannin, significantly abrogated the effects of GDNF on the levels of p-Akt/Akt, Bax and DNA fragmentation. However, a p38 mitogen-activated proten kinase (MAPK) inhibitor, SB203580, had no effect on the expression of p-Akt/Akt, Bax or DNA fragmentation. These results demonstrate the pivotal role of GDNF as well as the PI3K/Akt pathway, but not the MAPK pathway, in the prevention of diabetes-induced neuronal apoptosis in the hippocampus. PMID- 26549421 TI - Mining Discriminative Patterns from Graph Data with Multiple Labels and Its Application to Quantitative Structure-Activity Relationship (QSAR) Models. AB - Graph data are becoming increasingly common in machine learning and data mining, and its application field pervades to bioinformatics and cheminformatics. Accordingly, as a method to extract patterns from graph data, graph mining recently has been studied and developed rapidly. Since the number of patterns in graph data is huge, a central issue is how to efficiently collect informative patterns suitable for subsequent tasks such as classification or regression. In this paper, we consider mining discriminative subgraphs from graph data with multiple labels. The resulting task has important applications in cheminformatics, such as finding common functional groups that trigger multiple drug side effects, or identifying ligand functional groups that hit multiple targets. In computational experiments, we first verify the effectiveness of the proposed approach in synthetic data, then we apply it to drug adverse effect prediction problem. In the latter dataset, we compared the proposed method with L1-norm logistic regression in combination with the PubChem/Open Babel fingerprint, in that the proposed method showed superior performance with a much smaller number of subgraph patterns. Software is available from https://github.com/axot/GLP. PMID- 26549422 TI - alpha2A -Adrenergic receptor polymorphisms and mRNA expression levels are associated with delay discounting in cocaine users. AB - Cocaine users characteristically display preferences for smaller immediate rewards over larger delayed rewards, and this delay discounting (DD) has been proposed as an endophenotype of cocaine addiction. Recent evidence suggests that the norepinephrine system and more specifically the alpha2A -adrenergic receptor (ADRA2A) are impacted by chronic cocaine use while also being potentially involved in the neural mechanisms underlying DD. Hence, we investigated the effects of ADRA2A polymorphisms and ADRA2A mRNA expression levels on DD of cocaine users and stimulant-naive controls. Two hundred and twenty-three participants (129 cocaine users and 94 stimulant-naive healthy controls) completed a computerized DD paradigm and were genotyped for three single nucleotide polymorphisms (SNPs; rs1800544, rs521674 and rs602618) in the ADRA2A gene, while their peripheral ADRA2A mRNA expression was quantified in whole blood samples. The three SNPs were in near-perfect linkage disequilibrium. Accordingly, significant group*genotype interactions were found for all three ADRA2A variants revealing steeper DD in cocaine users (but not in controls) carrying the G-allele of SNP rs1800544, the T-allele of rs521674 and the C-allele of rs602618. Similarly, high ADRA2A mRNA expression levels were significantly associated with a reduced tendency to choose smaller more immediate rewards (over larger delayed rewards) in cocaine users but not in controls. As the relationship between DD and cocaine use was moderated by ADRA2A SNPs and by peripheral ADRA2A gene expression, we propose that the norepinephrine system is involved in DD deficits observed in cocaine using individuals. Consequently, pharmacological compounds targeting ADRA2As might be considered for the symptom-specific treatment of delay aversion in stimulant addiction. PMID- 26549423 TI - Methane partial oxidation using FeO(x)@La(0.8)Sr(0.2)FeO(3-delta) core-shell catalyst--transient pulse studies. AB - The chemical looping reforming (CLR) process, which utilizes a transition metal oxide based redox catalyst to partially oxidize methane to syngas, represents a potentially efficient approach for methane valorization. The CLR process inherently avoids costly cryogenic air separation by replacing gaseous oxygen with regenerable ionic oxygen (O(2-)) from the catalyst lattice. Our recent studies show that an Fe2O3@La0.8Sr0.2FeO3-delta core-shell redox catalyst is effective for CLR, as it combines the selectivity of an LSF shell with the oxygen capacity of an iron oxide core. The reaction between methane and the catalyst is also found to be highly dynamic, resulting from changes in lattice oxygen availability and surface properties. In this study, a transient pulse injection approach is used to investigate the mechanisms of methane partial oxidation over the Fe2O3@LSF redox catalyst. As confirmed by isotope exchange, the catalyst undergoes transitions between reaction "regions" with markedly different mechanisms. While oxygen evolution maintains a modified Mars-van Krevelen mechanism throughout the reaction with O(2-) conduction being the rate limiting step, the mechanism of methane conversion changes from an Eley-Rideal type in the first reaction region to a Langmuir-Hinshelwood-like mechanism in the third region. Availability of surface oxygen controls the reduction scheme of the catalyst and the underlying reaction mechanism. PMID- 26549424 TI - Potential of agricultural fungicides for antifungal drug discovery. AB - While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structure-activity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development. PMID- 26549425 TI - Constructing Highly Oriented Configuration by Few-Layer MoS2: Toward High Performance Lithium-Ion Batteries and Hydrogen Evolution Reactions. AB - Constructing three-dimensional (3D) architecture with oriented configurations by two-dimensional nanobuilding blocks is highly challenging but desirable for practical applications. The well-oriented open structure can facilitate storage and efficient transport of ion, electron, and mass for high-performance energy technologies. Using MoS2 as an example, we present a facile and effective hydrothermal method to synthesize 3D radially oriented MoS2 nanospheres. The nanosheets in the MoS2 nanospheres are found to have less than five layers with an expanded (002) plane, which facilitates storage and efficient transport of ion, electron, and mass. When evaluated as anode materials for rechargeable Li ion batteries, the MoS2 nanospheres show an outstanding performance; namely, a specific capacity as large as 1009.2 mA h g(-1) is delivered at 500 mA g(-1) even after 500 deep charge/discharge cycles. Apart from promising the lithium-ion battery anode, this 3D radially oriented MoS2 nanospheres also show high activity and stability for the hydrogen evolution reaction. PMID- 26549426 TI - Stepwise Formation of a 1,3-Butadiene Analogue of Mixed Heavier Group 15 Elements. AB - The reaction of the phosphinidene complex [Cp*P{W(CO)5}2] (1 a) with di-tert butylcarboimidophosphene leads to the P-C cage compound 6 and the Lewis acid-base adduct [Cp*P{W(CO)5}2(CNtBu)] (2 a). In contrast, the arsinidene complex shows a different reactivity. At low temperatures, the arsaphosphene complex [{W(CO)5}{eta(2)-(Cp*)As=P(tBu)}{W(CO)5}] (3) is formed. At these temperatures, 3 reacts further with a second equivalent of carboimidophosphene to form [{W(CO)5}{eta(2)-{(Cp*)(tBu)P}As=P(tBu)}{W(CO)5}] (5), probably by the insertion of a phosphinidene unit (tBuP) into an As-C bond. In contrast, at room temperature 3 reacts further by a radical-type reaction to form [{(tBu)P=As As=P(tBu)}{W(CO)5}4] (4). Compound 4 is the first example of a neutral, 1,3 butadiene analogue containing only mixed heavier Group 15 elements. It consists of two P=As double bonds connected by arsenic atoms. PMID- 26549427 TI - Expanded phylogenetic analyses of the class Heterotrichea (Ciliophora, Postciliodesmatophora) using five molecular markers and morphological data. AB - Most studies of the molecular evolution of Heterotrichea have been based solely on the 18S-rDNA gene, which were inconsistent with morphological classification. Because of the limitations of single locus phylogenies and the recurring problem of lack of resolution of deeper nodes found in previous studies, we present hypotheses of the evolution of internal groups of the class Heterotrichea based on multi-loci analyses (18S-rDNA, 28S-rDNA, ITS1-5.8S-ITS2 region, COI and alpha tubulin) and morphological data. Phylogenetic trees from protein coding gene data are presented for Heterotrichea for the first time. Phylogenetic analyses included Bayesian inference, maximum likelihood, maximum parsimony methods, and optimal trees were statistically compared to alternative topologies from the literature. Additionally, the Bayesian concordance approach (BCA algorithm) was used to assess the concordance factor between topologies obtained from isolated analyses. Because different loci may evolve at different rates, resulting in different gene topologies, we also estimated a species tree for Heterotrichea using the STAR coalescence-based method. The results show that: (1) single gene trees are inconsistent regarding the position of some heterotrichean families; (2) the concatenation of all data in a total-evidence tree improved the resolution of deep nodes among the heterotrichean families and genera; (3) the coalescent-based species tree is consistent with phylogenies based on the 18S rDNA gene and shows Spirostomidae as the stem group of Heterotrichea; (4) however, the total-evidence tree suggests that the large Heterotrichea cluster is divided into nine lineages in which Peritromidae diverges at the base of the Heterotrichea tree. PMID- 26549428 TI - Insect genome content phylogeny and functional annotation of core insect genomes. AB - Twenty-one fully sequenced and well annotated insect genomes were examined for genome content in a phylogenetic context. Gene presence/absence matrices and phylogenetic trees were constructed using several phylogenetic criteria. The role of e-value on phylogenetic analysis and genome content characterization is examined using scaled e-value cutoffs and a single linkage clustering approach to orthology determination. Previous studies have focused on the role of gene loss in terminals in the insect tree of life. The present study examines several common ancestral nodes in the insect tree. We suggest that the common ancestors of major insect groups like Diptera, Hymenoptera, Hemiptera and Holometabola experience more gene gain than gene loss. This suggests that as major insect groups arose, their genomic repertoire expanded through gene duplication (segmental duplications), followed by contraction by gene loss in specific terminal lineages. In addition, we examine the functional significance of the loss and gain of genes in the divergence of some of the major insect groups. PMID- 26549429 TI - Testing and Validation of Computational Methods for Mass Spectrometry. AB - High-throughput methods based on mass spectrometry (proteomics, metabolomics, lipidomics, etc.) produce a wealth of data that cannot be analyzed without computational methods. The impact of the choice of method on the overall result of a biological study is often underappreciated, but different methods can result in very different biological findings. It is thus essential to evaluate and compare the correctness and relative performance of computational methods. The volume of the data as well as the complexity of the algorithms render unbiased comparisons challenging. This paper discusses some problems and challenges in testing and validation of computational methods. We discuss the different types of data (simulated and experimental validation data) as well as different metrics to compare methods. We also introduce a new public repository for mass spectrometric reference data sets ( http://compms.org/RefData ) that contains a collection of publicly available data sets for performance evaluation for a wide range of different methods. PMID- 26549430 TI - Oxazolidinones as Anti-tubercular Agents: Discovery, Development and Future Perspectives. AB - TB drug development pipeline represents varied structural classes of molecules. Oxazolidinones represent synthetic anti-bacterial agents with unique mechanism of action having wide spectrum of activity, oral bioavailability and well established SAR. They act by inhibiting translation at the initiation phase of protein synthesis. Linezolid was the first oxazolidinone to reach the market in the year 2000 for the treatment of methicillin-resistant staphylococcal and vancomycin-resistant enterococcal infections. Oxazolidinones have shown very good anti-mycobacterial activities. Several oxazolidinones are currently in development for their possible use in TB therapy. Oxazolidinones are classified on the basis of C-ring modifications. DuP-721 was the first oxazolidinone having good anti-TB activity. Linezolid, sutezolid and AZD5847 are in clinical development. Several other C-ring modifications have shown promising results. The usefulness of these oxazolidinones in the drug resistant TB is already established. Toxicity, especially myelosuppression, has been an important limiting factor for their development. PMID- 26549431 TI - Histone Modifications as Molecular Targets in Nasopharyngeal Cancer. AB - Nasopharyngeal carcinoma (NPC) is a cancer of the nasopharyngeal epithelium with distinct geographical, ethnic and racial distribution. Several genetic, ethnic and environmental risk factors, have been implicated in nasopharyngeal pathogenesis and of significance, is the Epstein - Barr virus (EBV)- latent infection observed in most patients. Patients with NPC are typically diagnosed only in advanced stages due to non-specific symptoms, and hence, they respond poorly to therapy. Currently, low survival rates, severe complications, tumour metastasis and recurrence following chemo-radiotherapy, delineate the need for better therapeutic options to combat the disease. Recent studies have shown that epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs, which are altered in the EBV genome as well as in the host cells, may underlie the initiation and progression of NPC. Histone acetylation and deacetylation which are mediated by enzymes, namely histone acetyl transferases (HATs) and histone deacetylases (HDACs), are known to regulate gene expression and several cellular processes. HDACs are also involved in maintaining the EBV latent cycle and thus, HDAC inhibitors (HDACi) are potent inducers of EBV reactivation, which is critical for the expression of the lytic proteins, thereby providing novel targets for therapy, as well as mediating enhanced killing of cancer cells, when used alone or along with additional anti-cancer agents in EBV associated malignancies. Recently, three FDA- approved HDACi have been used for the treatment of T-cell lymphoma, while several others are in clinical trials, making histone modifications excellent candidates for targeted therapy. In this review, we summarize the epigenetic mechanisms altered in NPC, with a focus on histone modifications for targeted therapy. PMID- 26549432 TI - 2D mammography, digital breast tomosynthesis, and ultrasound: which should be used for the different breast densities in breast cancer screening? AB - PURPOSE: To determine which modalities [2D mammography (2D), digital breast tomosynthesis (DBT), whole breast sonography (WBS)] are optimal for screening depending on breast density. METHODS: Institutional retrospective cohort study of 2013 screening mammograms (16,789), sorted by modalities and density. RESULTS: Cancer detection is increased by adding WBS to 2D (P=.02) for the overall study population. Recall rate was lowest with 2D+DBT (10.2%, P<.001) and highest with 2D+DBT+WBS (23.6%, P<.001) for the overall study population as well. CONCLUSION: Women with dense and nondense breasts benefit from reduced recall rate with the addition of DBT; however, this benefit is negated with the addition of WBS. PMID- 26549433 TI - "Away Days" in multicenter randomized controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment. AB - OBJECTIVE: "Away Days" (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multicenter randomized controlled trials (RCTs). We explored the use of Away Days in multicenter RCTs and analyzed the effect on patient recruitment in a case study. METHODS: Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multicenter pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. RESULTS: A total of 94 people responded to the survey. The majority (78%), who confirmed had organized an Away Day previously, found them to be useful. This is despite their costs. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. CONCLUSIONS: Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multicenter surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design, and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. PMID- 26549434 TI - Intercalation crystallization of phase-pure alpha-HC(NH2)2PbI3 upon microstructurally engineered PbI2 thin films for planar perovskite solar cells. AB - The microstructure of the solid-PbI2 precursor thin film plays an important role in the intercalation crystallization of the formamidinium lead triiodide perovskite (alpha-HC(NH2)2PbI3). It is shown that microstructurally engineered PbI2 thin films with porosity and low crystallinity are the most favorable for conversion into uniform-coverage, phase-pure alpha-HC(NH2)2PbI3 perovskite thin films. Planar perovskite solar cells fabricated using these thin films deliver power conversion efficiency (PCE) up to 13.8%. PMID- 26549435 TI - Evaluation of quality of anesthesia and analgesia and of vital signs after intramuscular administration of a combination of butorphanol, medetomidine and alfaxalone in cats. AB - This study evaluated the quality of anesthesia, duration of analgesia and changes in vital signs after intramuscular administration of a combination of butorphanol, medetomidine and alfaxalone in domestic cats. Ten healthy adult domestic cats (weighing 2.9 +/- 0.5 kg) were used in this study. Rectal temperature (T), pulse rate (PR), respiratory rate (fR) and systolic arterial pressure (SAP) were measured and recorded prior to intramuscular (IM) administration of butorphanol (0.2 mg/kg), medetomidine (20 ug/kg) and alfaxalone (5 mg/kg) and then every 10 min until return of consciousness. Qualitative scores for induction of anesthesia and recovery were allocated, duration of anesthesia and recovery were calculated, and adverse events were recorded. A needle prick with a 22-gauge hypodermic needle was used to assess analgesia. Scores for induction and recovery quality were acceptable. No significant adverse events except nausea (7/10) and vomiting (5/10) were observed. The mean +/- SD times from induction to extubation and to standing (full recovery) were 114 +/- 8 and 125 +/- 7 min, respectively. There were statistically significant changes in PR, fR and SAP after induction of anesthesia. The combination of butorphanol, medetomidine and alfaxalone provided acceptable quality of anesthesia and analgesia and exerted minimal cardiopulmonary effects in domestic cats. PMID- 26549436 TI - The epidemiological survey for atovaquone resistant related gene of Babesia gibsoni in Japan. AB - In 73 gDNA samples from Babesia gibsoni-infected dogs, the M121I variant population was measured by using allele-specific real-time PCR. Although the mechanism of atovaquone against B. gibsoni has not been clearly identified, it is reported that the mitochondria cytochrome b gene of the atovaquone-resistant B. gibsoni had a single-nucleotide substitution at nt363 (G to T), which resulted in the substitution of methionine with isoleucine (M121I). In this study, 3/73 samples showed over 5% M121I variant population. Although the M121I variant population is a low percentage, it runs the risk of spreading drug-resistant parasites. It is important to prevent the spread of drug-resistance, so we need to gather information about this at regular intervals. PMID- 26549437 TI - The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation. AB - Currently, drug discovery and development for clinical treatment of prostate cancer has received increased attention, specifically the STAT3 inhibitor. Our previous study reported that the neuroleptic drug pimozide had antitumor activity against hepatocellular carcinoma cells or stem-like cells through suppressing the STAT3 activity. In the present study we demonstrate that pimozide inhibits cell growth and cellular STAT3 activation in prostate cancer cells. Our results showed that pimozide inhibited prostate cancer cell proliferation in a dose- and time dependent manner by inducing G1 phase cell cycle arrest, downregulated the ability of colony formation and sphere forming, as well as suppressed cells migration in both DU145 and LNCaP cells. Surprisingly, pimozide reduced the basal expression of phosphorylation STAT3 at tyrosine 705 and reversed the expression of phosphorylation of STAT3 induced by IL-6 addition, suggesting that pimozide can suppress cellular STAT3 activation. Thus, the antipsychotic agent pimozide may be a potential and novel therapeutic for patients with advanced prostate cancer. PMID- 26549438 TI - Creating orbiting vorticity vectors in magnetic particle suspensions through field symmetry transitions-a route to multi-axis mixing. AB - It has recently been reported that two types of triaxial electric or magnetic fields can drive vorticity in dielectric or magnetic particle suspensions, respectively. The first type-symmetry-breaking rational fields-consists of three mutually orthogonal fields, two alternating and one dc, and the second type rational triads-consists of three mutually orthogonal alternating fields. In each case it can be shown through experiment and theory that the fluid vorticity vector is parallel to one of the three field components. For any given set of field frequencies this axis is invariant, but the sign and magnitude of the vorticity (at constant field strength) can be controlled by the phase angles of the alternating components and, at least for some symmetry-breaking rational fields, the direction of the dc field. In short, the locus of possible vorticity vectors is a 1-d set that is symmetric about zero and is along a field direction. In this paper we show that continuous, 3-d control of the vorticity vector is possible by progressively transitioning the field symmetry by applying a dc bias along one of the principal axes. Such biased rational triads are a combination of symmetry-breaking rational fields and rational triads. A surprising aspect of these transitions is that the locus of possible vorticity vectors for any given field bias is extremely complex, encompassing all three spatial dimensions. As a result, the evolution of a vorticity vector as the dc bias is increased is complex, with large components occurring along unexpected directions. More remarkable are the elaborate vorticity vector orbits that occur when one or more of the field frequencies are detuned. These orbits provide the basis for highly effective mixing strategies wherein the vorticity axis periodically explores a range of orientations and magnitudes. PMID- 26549440 TI - Aqueous extraction of pectin from sour orange peel and its preliminary physicochemical properties. AB - Sour orange peel, a by-product of the fruit juice industry, was used as a source of pectin. The effects of temperature (75-95 degrees C), time (30-90 min), and liquid-solid ratio (20-40, v/w) were investigated on yield, methoxylation degree (DE), and galacturonic acid content using a Box-Behnken design and response surface methodology. The highest extraction yield (17.95 +/- 0.3%) was obtained at temperature of 95 degrees C, time of 90 min, and liquid-solid ratio of 25 (v/w). The DE values for the pectin ranged from 17% to 30.5%, indicating that the pectin was low in methoxyle. The emulsifying activity of pectin extracted under optimal conditions was 45%. The emulsions were 86.6% stable at 4 degrees C and 71.4% at 23 degrees C after 30 days of storage. The pectin exhibited Newtonian flow at low concentrations (<= 1.0%, w/v); as the concentration increased, pseudoplastic flow became dominant. PMID- 26549439 TI - KCNK5 channels mostly expressed in cochlear outer sulcus cells are indispensable for hearing. AB - In the cochlea, K(+) is essential for mechano-electrical transduction. Here, we explore cochlear structure and function in mice lacking K(+) channels of the two pore domain family. A profound deafness associated with a decrease in endocochlear potential is found in adult Kcnk5(-/-) mice. Hearing occurs around postnatal day 19 (P19), and completely disappears 2 days later. At P19, Kcnk5(-/ ) mice have a normal endolymphatic [K(+)] but a partly lowered endocochlear potential. Using Lac-Z as a gene reporter, KCNK5 is mainly found in outer sulcus Claudius', Boettcher's and root cells. Low levels of expression are also seen in the spiral ganglion, Reissner's membrane and stria vascularis. Essential channels (KCNJ10 and KCNQ1) contributing to K(+) secretion in stria vascularis have normal expression in Kcnk5(-/-) mice. Thus, KCNK5 channels are indispensable for the maintenance of hearing. Among several plausible mechanisms, we emphasize their role in K(+) recycling along the outer sulcus lateral route. PMID- 26549441 TI - Microwave assisted synthesis and characterization of sodium alginate-graft poly(N,N'-dimethylacrylamide). AB - Modification of sodium alginate (NaAlg) was carried out using N,N' dimethylacrylamide (DMAAm) as a monomer and azobisizobutyronitrile (AIBN) as an initiator under microwave irradiation. The effect of reaction conditions such as concentrations of DMAAm, AIBN, NaAlg as well as microwave power and temperature on grafting and grafting efficiency has been explored. Maximum grafting and grafting efficiency has been observed at 1h of grafting time, 0.291 M of DMAAm concentration, 500 W microwave irradiation power, 0.134 M of AIBN concentration, 75 degrees C of reaction temperature and 0.5 g/dL of NaAlg concentration. The grafted copolymer has been characterized by FTIR, DSC, TGA, (13)C NMR, XRD, SEM, and GPC analysis. Cytotoxicity as standard MTT assay, apoptotic and necrotic effects of graft copolymer were investigated on L929 fibroblast cell. It has been found that the grafted copolymer is biocompatible and thermally more stable than the ungrafted alginate. PMID- 26549442 TI - The Stereociliary Paracrystal Is a Dynamic Cytoskeletal Scaffold In Vivo. AB - Permanency of mechanosensory stereocilia may be the consequence of low protein turnover or rapid protein renewal. Here, we devise a system, using optical techniques in live zebrafish, to distinguish between these mechanisms. We demonstrate that the stereocilium's abundant actin cross-linker fascin 2b exchanges, without bias or a phosphointermediate, orders of magnitude faster (t1/2 of 76.3 s) than any other known hair bundle protein. To establish the logic of fascin 2b's exchange, we examine whether filamentous actin is dynamic and detect substantial beta-actin exchange within the stereocilium's paracrystal (t1/2 of 4.08 hr). We propose that fascin 2b's behavior may enable cross-linking at fast timescales of stereocilia vibration while noninstructively facilitating the slower process of actin exchange. Furthermore, tip protein myosin XVa fully exchanges in hours (t1/2 of 11.6 hr), indicating that delivery of myosin associated cargo occurs in mature stereocilia. These findings suggest that stereocilia permanency is underpinned by vibrant protein exchange. PMID- 26549443 TI - Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization. AB - For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man. PMID- 26549444 TI - Organization of the Mammalian Ionome According to Organ Origin, Lineage Specialization, and Longevity. AB - Trace elements are essential to all mammals, but their distribution and utilization across species and organs remains unclear. Here, we examined 18 elements in the brain, heart, kidney, and liver of 26 mammalian species and report the elemental composition of these organs, the patterns of utilization across the species, and their correlation with body mass and longevity. Across the organs, we observed distinct distribution patterns for abundant elements, transition metals, and toxic elements. Some elements showed lineage-specific patterns, including reduced selenium utilization in African mole rats, and positive correlation between the number of selenocysteine residues in selenoprotein P and the selenium levels in liver and kidney across mammals. Body mass was linked positively to zinc levels, whereas species lifespan correlated positively with cadmium and negatively with selenium. This study provides insights into the variation of mammalian ionome by organ physiology, lineage specialization, body mass, and longevity. PMID- 26549445 TI - RACK1 Promotes Autophagy by Enhancing the Atg14L-Beclin 1-Vps34-Vps15 Complex Formation upon Phosphorylation by AMPK. AB - Autophagy is essential for maintaining tissue homeostasis. Although adaptors have been demonstrated to facilitate the assembly of the Atg14L-Beclin 1-Vps34-Vps15 complex, which functions in autophagosome formation, it remains unknown whether the autophagy machinery actively recruits such adaptors. WD40-repeat proteins are a large, highly conserved family of adaptors implicated in various cellular activities. However, the role of WD40-repeat-only proteins, such as RACK1, in postnatal mammalian physiology remains unknown. Here, we report that hepatocyte specific RACK1 deficiency leads to lipid accumulation in the liver, accompanied by impaired Atg14L-linked Vps34 activity and autophagy. Further exploration indicates that RACK1 participates in the formation of autophagosome biogenesis complex upon its phosphorylation by AMPK at Thr50. Thr50 phosphorylation of RACK1 enhances its direct binding to Vps15, Atg14L, and Beclin 1, thereby promoting the assembly of the autophagy-initiation complex. These observations provide insight into autophagy induction and establish a pivotal role for RACK1 in postnatal mammalian physiology. PMID- 26549446 TI - Interneuronal Nitric Oxide Signaling Mediates Post-synaptic Long-Term Depression of Striatal Glutamatergic Synapses. AB - Experience-driven plasticity of glutamatergic synapses on striatal spiny projection neurons (SPNs) is thought to be essential to goal-directed behavior and habit formation. One major form of striatal plasticity, long-term depression (LTD), has long appeared to be expressed only pre-synaptically. Contrary to this view, nitric oxide (NO) generated by striatal interneurons was found to induce a post-synaptically expressed form of LTD at SPN glutamatergic synapses. This form of LTD was dependent on signaling through guanylyl cyclase and protein kinase G, both of which are abundantly expressed by SPNs. NO-LTD was unaffected by local synaptic activity or antagonism of endocannabinoid (eCb) and dopamine receptors, all of which modulate canonical, pre-synaptic LTD. Moreover, NO signaling disrupted induction of this canonical LTD by inhibiting dendritic Ca(2+) channels regulating eCb synthesis. These results establish an interneuron-dependent, heterosynaptic form of post-synaptic LTD that could act to promote stability of the striatal network during learning. PMID- 26549447 TI - A Testis-Specific Chaperone and the Chromatin Remodeler ISWI Mediate Repackaging of the Paternal Genome. AB - During spermatogenesis, the paternal genome is repackaged into a non-nucleosomal, highly compacted chromatin structure. Bioinformatic analysis revealed that Drosophila sperm chromatin proteins are characterized by a motif related to the high-mobility group (HMG) box, which we termed male-specific transcript (MST)-HMG box. MST77F is a MST-HMG-box protein that forms an essential component of sperm chromatin. The deposition of MST77F onto the paternal genome requires the chaperone function of tNAP, a testis-specific NAP protein. MST77F, in turn, enables the stable incorporation of MST35Ba and MST35Bb into sperm chromatin. Following MST-HMG-box protein deposition, the ATP-dependent chromatin remodeler ISWI mediates the appropriate organization of sperm chromatin. Conversely, at fertilization, maternal ISWI targets the paternal genome and drives its repackaging into de-condensed nucleosomal chromatin. Failure of this transition in ISWI mutant embryos is followed by mitotic defects, aneuploidy, and haploid embryonic divisions. Thus, ISWI enables bi-directional transitions between two fundamentally different forms of chromatin. PMID- 26549448 TI - Low-Cell-Number Epigenome Profiling Aids the Study of Lens Aging and Hematopoiesis. AB - Understanding how chromatin modification regulates development and disease can be limited by available material. Despite recent progress, balancing high-quality and reliable mapping using chromatin-immunoprecipitation-based deep sequencing (ChIP-seq) remains a challenge. We report two techniques, recovery via protection (RP)-ChIP-seq and favored amplification RP-ChIP-seq (FARP-ChIP-seq), that provide reproducible mapping in as few as 500 cells. RP-ChIP-seq allows detection of age associated epigenetic changes in a single mouse lens, whereas FARP-ChIP-seq accurately maps histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in long term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), and multi potent progenitors (MPPs) from one mouse. These datasets not only highlight genes that may be involved in lens aging but also indicate a lack of H3K4me3/H3K27me3 bivalency on hematopoietic genes in HSCs. PMID- 26549449 TI - Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways. AB - The central question in stem cell regulation is how the balance between self renewal and differentiation is controlled at the molecular level. This study uses germline stem cells (GSCs) in the Drosophila ovary to demonstrate that the Drosophila CCR4 homolog Twin is required intrinsically to promote both GSC self renewal and progeny differentiation. Twin/CCR4 is one of the two catalytic subunits in the highly conserved CCR4-NOT mRNA deadenylase complex. Twin works within the CCR4-NOT complex to intrinsically maintain GSC self-renewal, at least partly by sustaining E-cadherin-mediated GSC-niche interaction and preventing transposable element-induced DNA damage. It promotes GSC progeny differentiation by forming protein complexes with differentiation factors Bam and Bgcn independently of other CCR4-NOT components. Interestingly, Bam can competitively inhibit the association of Twin with Pop2 in the CCR4-NOT complex. Therefore, this study demonstrates that Twin has important intrinsic roles in promoting GSC self-renewal and progeny differentiation by functioning in different protein complexes. PMID- 26549451 TI - Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair. AB - The nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome (HGPS). SIRT6 deficiency leads to defective genomic maintenance and accelerated aging similar to HGPS, suggesting a potential link between lamin A and SIRT6. Here, we report that lamin A is an endogenous activator of SIRT6 and facilitates chromatin localization of SIRT6 upon DNA damage. Lamin A promotes SIRT6-dependent DNA-PKcs (DNA-PK catalytic subunit) recruitment to chromatin, CtIP deacetylation, and PARP1 mono-ADP ribosylation in response to DNA damage. The presence of progerin jeopardizes SIRT6 activation and compromises SIRT6-mediated molecular events in response to DNA damage. These data reveal a critical role for lamin A in regulating SIRT6 activities, suggesting that defects in SIRT6 functions contribute to impaired DNA repair and accelerated aging in HGPS. PMID- 26549450 TI - An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens. AB - There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ~3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical chemical interactions termed the Antifungal Combinations Matrix (ACM). Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens. PMID- 26549452 TI - PTEN Controls the DNA Replication Process through MCM2 in Response to Replicative Stress. AB - PTEN is a tumor suppressor frequently mutated in human cancers. PTEN inhibits the phosphatidylinositol 3-kinase (PI3K)-AKT cascade, and nuclear PTEN guards the genome by multiple mechanisms. Here, we report that PTEN physically associates with the minichromosome maintenance complex component 2 (MCM2), which is essential for DNA replication. Specifically, PTEN dephosphorylates MCM2 at serine 41 (S41) and restricts replication fork progression under replicative stress. PTEN disruption results in unrestrained fork progression upon replication stalling, which is similar to the phenotype of cells expressing the phosphomimic MCM2 mutant S41D. Moreover, PTEN is necessary for prevention of chromosomal aberrations under replication stress. This study demonstrates that PTEN regulates DNA replication through MCM2 and loss of PTEN function leads to replication defects and genomic instability. We propose that PTEN plays a critical role in maintaining genetic stability through a replication-specific mechanism, and this is a crucial facet of PTEN tumor suppressor activity. PMID- 26549453 TI - Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control. AB - The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson's disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD) by inhibiting small conductance Ca(2+)-activated K(+) channels (SKs) of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB)-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control. PMID- 26549454 TI - Slow-gamma Rhythms Coordinate Cingulate Cortical Responses to Hippocampal Sharp Wave Ripples during Wakefulness. AB - Behavioral changes in response to reward require monitoring past behavior relative to present outcomes. This is thought to involve a fine coordination between the hippocampus (HIPP), which stores and replays memories of past events, and cortical regions such as cingulate cortex, responsible for behavioral planning. Sharp-wave ripple (SWR)-mediated memory replay in the HIPP of awake rodents contributes to learning, but cortical responses to hippocampal SWR during wakefulness are not known. We now show that in rats, during quiet-wakefulness, cingulate neurons exhibit significant responses to SWR, as well as increased modulation by the accompanying hippocampal local field potential slow-gamma oscillation, a rhythm associated with intra-hippocampal information processing. The magnitude of cingulate neurons' responses to SWR is significantly correlated with the degree of their modulation by HIPP slow-gamma. We hypothesize that during pauses cingulate neurons transiently access episodic information concerning previous choices, replayed by HIPP SWR, to evaluate past trajectories in light of their outcome. PMID- 26549456 TI - Genomic Alterations in CIITA Are Frequent in Primary Mediastinal Large B Cell Lymphoma and Are Associated with Diminished MHC Class II Expression. AB - Primary mediastinal large B cell lymphoma (PMBCL) is an aggressive non-Hodgkin's lymphoma, predominantly affecting young patients. We analyzed 45 primary PMBCL tumor biopsies and 3 PMBCL-derived cell lines for the presence of genetic alterations involving the major histocompatibility complex (MHC) class II transactivator CIITA and found frequent aberrations consisting of structural genomic rearrangements, missense, nonsense, and frame-shift mutations (53% of primary tumor biopsies and all cell lines). We also detected intron 1 mutations in 47% of the cases, and detailed sequence analysis strongly suggests AID mediated aberrant somatic hypermutation as the mutational mechanism. Furthermore, we demonstrate that genomic lesions in CIITA result in decreased protein expression and reduction of MHC class II surface expression, creating an immune privilege phenotype in PMBCL. In summary, we establish CIITA alterations as a common mechanism of immune escape through reduction of MHC class II expression in PMBCL, with potential implications for future treatments targeting microenvironment-related biology. PMID- 26549455 TI - Engineered Mammalian RNAi Can Elicit Antiviral Protection that Negates the Requirement for the Interferon Response. AB - Although the intrinsic antiviral cell defenses of many kingdoms utilize pathogen specific small RNAs, the antiviral response of chordates is primarily protein based and not uniquely tailored to the incoming microbe. In an effort to explain this evolutionary bifurcation, we determined whether antiviral RNAi was sufficient to replace the protein-based type I interferon (IFN-I) system of mammals. To this end, we recreated an RNAi-like response in mammals and determined its effectiveness to combat influenza A virus in vivo in the presence and absence of the canonical IFN-I system. Mammalian antiviral RNAi, elicited by either host- or virus-derived small RNAs, effectively attenuated virus and prevented disease independently of the innate immune response. These data find that chordates could have utilized RNAi as their primary antiviral cell defense and suggest that the IFN-I system emerged as a result of natural selection imposed by ancient pathogens. PMID- 26549457 TI - Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage Restricted Cells Rather Than Bipotent Progenitors. AB - Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe beta5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe beta5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult beta5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal beta5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny. PMID- 26549458 TI - Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery. AB - Transcription elongation regulates the expression of many genes, including oncogenes. Histone deacetylase (HDAC) inhibitors (HDACIs) block elongation, suggesting that HDACs are involved in gene activation. To understand this, we analyzed nascent transcription and elongation factor binding genome-wide after perturbation of elongation with small molecule inhibitors. We found that HDACI mediated repression requires heat shock protein 90 (HSP90) activity. HDACIs promote the association of RNA polymerase II (RNAP2) and negative elongation factor (NELF), a complex stabilized by HSP90, at the same genomic sites. Additionally, HDACIs redistribute bromodomain-containing protein 4 (BRD4), a key elongation factor involved in enhancer activity. BRD4 binds to newly acetylated sites, and its occupancy at promoters and enhancers is reduced. Furthermore, HDACIs reduce enhancer activity, as measured by enhancer RNA production. Therefore, HDACs are required for limiting acetylation in gene bodies and intergenic regions. This facilitates the binding of elongation factors to properly acetylated promoters and enhancers for efficient elongation. PMID- 26549459 TI - Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells. AB - Variation in the level of mtDNA heteroplasmy in adult tissues is commonly seen in patients with a mixture of wild-type and mutant mtDNA. A mixture of different mtDNA variants may influence such variation and cause mtDNA segregation bias. We analyzed cellular heterogeneity in embryonic stem cells (ESCs) derived from a polymorphic mouse model containing NZB and BALB mtDNA genotypes. In ESCs, inter colony heterogeneity varied up to 61%, whereas intra-colony heterogeneity varied up to 100%. Three out of five cell lines displayed nearly homoplasmic BALB and NZB mtDNA haplotypes in differentiated single cells. The proportion of NZB mtDNA genotype increased with progressive passaging (0.39%; p = 0.002). These results demonstrate the bimodal segregation of mtDNA haplotypes, indicating the occurrence of tissues with variable levels of heteroplasmies in individuals with mtDNA mutations. Furthermore, proliferation of one mtDNA genotype over another may pose the risk of accumulating mutant mtDNAs during subsequent cell divisions. PMID- 26549461 TI - DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium. AB - VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb(-/-) embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis. PMID- 26549460 TI - Global Reprogramming of Host SUMOylation during Influenza Virus Infection. AB - Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID- 26549462 TI - Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters. AB - Primiparous ewes (n=32) were assigned to dietary treatments in a 2*2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P?0.001) maternal pancreatic mass (g) and alpha-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and alpha-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 um2) and giant (?512 001 um2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P?0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 um2) while fetuses had more (P<0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters (P?0.02). Larger insulin-containing clusters were observed in fetuses (P<0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased alpha amylase content. Nutrient restriction decreased the number of pancreatic insulin containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial. PMID- 26549463 TI - Integrins and haptoglobin: Molecules overexpressed in ovarian cancer. AB - Integrins are adhesion molecules whose expression is upregulated during different cellular processes such as adhesion, growth, proliferation, migration, survival and differentiation, all of which are involved in neoplastic development. Several reports have linked the overexpression of integrins with epithelial ovarian cancer (EOC). Furthermore, fucosylated haptoglobin (Hp) isoforms with antioxidant activity and synthesized primarily in the liver have also been associated with various types of cancer, including ovarian cancer. Here, we determined the level of expression of three integrin heterodimers (alpha5beta1, alpha6beta4, and alphaVbeta3) and fucosyltated Hp in two different settings: cell cultures and biopsies from ovarian cancer patients. On the one hand, integrin heterodimers were analyzed in the ovarian cancer cell line (SKOV-3), two primary cultures (INCan017 and INCan019) and a tumor derived from INCan017 (T-017) by Western blot. Statistical analysis was performed using one-way ANOVA. The SKOV-3 cell line, INCan017 and INCan019 primary cultures, and the T-017 tumor showed increased expression patterns of the alpha5, alphaV, beta1, beta3, and beta4 integrin subunits when compared with healthy ovary tissue. We then analyzed the expression pattern of the integrin subunits as well as the fucosylated Hp in biopsies from patients with different histotypes of EOC by immunofluorescence. alpha5beta1 and alpha6beta4 integrins were expressed by 90% of the samples, whereas 80% expressed the alphaVbeta3 integrin. Furthermore, Hp, fucosylated or not, was present at high levels in most biopsies. In fact, there was a statistical correlation between the expression of integrins or Hp and the presence of the disease given that alpha5beta1, alpha6beta4, and alphaVbeta3 integrins, Hp, fucosylated Hp and additional fucosylation state of proteins were highly expressed in biopsies of EOC histotypes when compared with healthy ovarian tissue. However, the statistical analysis showed no association of the presence of integrins, Hp or fucosylation with clinical or pathological characteristics of EOC patients. These results suggest that increased expression of these molecules and of the fucosylation modification are characteristics of the malignant process itself. Therefore, these molecules may be promising therapeutic targets in patients with this type of neoplasia. PMID- 26549464 TI - The Biarzo case in northern Italy: is the temporal dynamic of swine mitochondrial DNA lineages in Europe related to domestication? AB - Genetically-based reconstructions of the history of pig domestication in Europe are based on two major pillars: 1) the temporal changes of mitochondrial DNA lineages are related to domestication; 2) Near Eastern haplotypes which appeared and then disappeared in some sites across Europe are genetic markers of the first Near Eastern domestic pigs. We typed a small but informative fragment of the mitochondrial DNA in 23 Sus scrofa samples from a site in north eastern Italy (Biarzo shelter) which provides a continuous record across a ~6,000 year time frame from the Upper Palaeolithic to the Neolithic. We additionally carried out several radiocarbon dating. We found that a rapid mitochondrial DNA turnover occurred during the Mesolithic, suggesting that substantial changes in the composition of pig mitochondrial lineages can occur naturally across few millennia independently of domestication processes. Moreover, so-called Near Eastern haplotypes were present here at least two millennia before the arrival of Neolithic package in the same area. Consequently, we recommend a re-evaluation of the previous idea that Neolithic farmers introduced pigs domesticated in the Near East, and that Mesolithic communities acquired domestic pigs via cultural exchanges, to include the possibility of a more parsimonious hypothesis of local domestication in Europe. PMID- 26549465 TI - Implementation of the malaria candidate vaccine RTS,S/AS01. PMID- 26549467 TI - A balanced secondary structure predictor. AB - Secondary structure (SS) refers to the local spatial organization of a polypeptide backbone atoms of a protein. Accurate prediction of SS can provide crucial features to form the next higher level of 3D structure of a protein accurately. SS has three different major components, helix (H), beta (E) and coil (C). Most of the SS predictors express imbalanced accuracies by claiming higher prediction performances in predicting H and C, and on the contrary having low accuracy in E predictions. E component being in low count, a predictor may show very good overall performance by over-predicting H and C and under predicting E, which can make such predictors biologically inapplicable. In this work we are motivated to develop a balanced SS predictor by incorporating 33 physicochemical properties into 15-tuble peptides via Chou's general PseAAC, which allowed obtaining higher accuracies in predicting all three SS components. Our approach uses three different support vector machines for binary classification of the major classes and then form optimized multiclass predictor using genetic algorithm (GA). The trained three binary SVMs are E versus non-E (i.e., E/!E), C/!C and H/!H. This GA based optimized and combined three class predictor, called cSVM, is further combined with SPINE X to form the proposed final balanced predictor, called MetaSSPred. This novel paradigm assists us in optimizing the precision and recall. We prepared two independent test datasets (CB471 and N295) to compare the performance of our predictors with SPINE X. MetaSSPred significantly increases beta accuracy (QE) for both the datasets. QE score of MetaSSPred on CB471 and N295 were 71.7% and 74.4% respectively. These scores are 20.9% and 19.0% improvement over the QE scores given by SPINE X alone on CB471 and N295 datasets respectively. Standard deviations of the accuracies across three SS classes of MetaSSPred on CB471 and N295 datasets were 4.2% and 2.3% respectively. On the other hand, for SPINE X, these values are 12.9% and 10.9% respectively. These findings suggest that the proposed MetaSSPred is a well balanced SS predictor compared to the state-of-the-art SPINE X predictor. PMID- 26549466 TI - Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models. AB - BACKGROUND: The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. METHODS: We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5-17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2-10 year olds (PfPR2-10; range 3-65%). We considered two vaccine schedules: three doses at ages 6, 7.5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2-10 per dose. FINDINGS: In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93,940 (range 20,490 126,540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116,480 (31,450-160,410) clinical cases and 484 (189-859) deaths for the four dose schedule, per 100,000 fully vaccinated children. A positive impact is also predicted at a PfPR2-10 of 5-10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18-211) per clinical case averted and $80 (44-279) per DALY averted for the three-dose schedule, and of $25 (16-222) and $87 (48-244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2-10 levels. INTERPRETATION: We predict a significant public health impact and high cost effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. FUNDING: PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO. PMID- 26549468 TI - PAM: Particle automata model in simulation of Fusarium graminearum pathogen expansion. AB - The multi-scale nature and inherent complexity of biological systems are a great challenge for computer modeling and classical modeling paradigms. We present a novel particle automata modeling metaphor in the context of developing a 3D model of Fusarium graminearum infection in wheat. The system consisting of the host plant and Fusarium pathogen cells can be represented by an ensemble of discrete particles defined by a set of attributes. The cells-particles can interact with each other mimicking mechanical resistance of the cell walls and cell coalescence. The particles can move, while some of their attributes can be changed according to prescribed rules. The rules can represent cellular scales of a complex system, while the integrated particle automata model (PAM) simulates its overall multi-scale behavior. We show that due to the ability of mimicking mechanical interactions of Fusarium tip cells with the host tissue, the model is able to simulate realistic penetration properties of the colonization process reproducing both vertical and lateral Fusarium invasion scenarios. The comparison of simulation results with micrographs from laboratory experiments shows encouraging qualitative agreement between the two. PMID- 26549469 TI - An evolutionary stability perspective on oncogenesis control in mature T-cell populations. AB - Here we present a mathematical model for the dynamics of oncogenesis control in mature T-cell populations within the blood and lymphatic system. T-cell homeostasis is maintained by clonal competition for trophic niches (survival signals stimulated through interactions with self-antigens bound to major histocompatibility molecules), where a clone is defined as the set of T cells carrying the same antigen specific T-cell receptor (TCR). We analytically derive fitness functions of healthy and leukemic clone variants, respectively, that capture the dependency of the stability of the healthy T-cell pool against leukemic invaders on clonal diversity and kinetic parameters. Similar to the stability of ecosystems with high biodiversity, leukemic mutants are suppressed within polyclonal T-cell populations, i.e., in the presence of a huge number of different TCRs. To the contrary, for a low clonal diversity the leukemic clone variants are able to invade the healthy T-cell pool. The model, therefore, describes the experimentally observed phenomenon that preleukemic clone variants prevail in quasi-monoclonal experimental settings (in mice), whereas in polyclonal settings the healthy TCR variants are able to suppress the outgrowth of tumours. Between the two extremal situations of mono- and polyclonality there exists a range of coexistence of healthy and oncogenic clone variants with moderate fitness (stability) each. A variation of cell cycle times considerably changes the dynamics within this coexistence region. Faster proliferating variants increase their chance to dominate. Finally, a simplified niche variation scheme illustrates a possible mechanism to increase clonal T-cell diversity given a small niche diversity. PMID- 26549470 TI - A biophysical model of cell evolution after cytotoxic treatments: Damage, repair and cell response. AB - We present a theoretical agent-based model of cell evolution under the action of cytotoxic treatments, such as radiotherapy or chemotherapy. The major features of cell cycle and proliferation, cell damage and repair, and chemical diffusion are included. Cell evolution is based on a discrete Markov chain, with cells stepping along a sequence of discrete internal states from 'normal' to 'inactive'. Probabilistic laws are introduced for each type of event a cell can undergo during its life: duplication, arrest, senescence, damage, reparation, or death. We adjust the model parameters on a series of cell irradiation experiments, carried out in a clinical LINAC, in which the damage and repair kinetics of single- and double-strand breaks are followed. Two showcase applications of the model are then presented. In the first one, we reconstruct the cell survival curves from a number of published low- and high-dose irradiation experiments. We reobtain a very good description of the data without assuming the well-known linear-quadratic model, but instead including a variable DSB repair probability. The repair capability of the model spontaneously saturates to an exponential decay at increasingly high doses. As a second test, we attempt to simulate the two extreme possibilities of the so-called 'bystander' effect in radiotherapy: the 'local' effect versus a 'global' effect, respectively activated by the short range or long-range diffusion of some factor, presumably secreted by the irradiated cells. Even with an oversimplified simulation, we could demonstrate a sizeable difference in the proliferation rate of non-irradiated cells, the proliferation acceleration being much larger for the global than the local effect, for relatively small fractions of irradiated cells in the colony. PMID- 26549471 TI - In reply: Predictability of prevention of hypoxia by nasal high-flow system in dental procedures. PMID- 26549472 TI - Special Contribution: Third Molar Clinical Trials Annotated Bibliography. AB - PURPOSE: To provide clinicians with an annotated bibliography of published articles from research funded externally by the Oral and Maxillofacial Surgery Foundation, spanning 1996 to 2015, addressing the topic of third molar management. MATERIALS AND METHODS: A brief summary for each article was generated by the respective authors. RESULTS: The complete annotated bibliography generated by the authors is included in the Appendix. CONCLUSION: The annotated bibliography provides clinicians and other interested individuals with a summary of current literature emanating from clinical studies on third molar topics. PMID- 26549473 TI - Oral Surgical Procedures Performed Safely in Patients With Head and Neck Arteriovenous Malformations: A Retrospective Case Series of 12 Patients. AB - PURPOSE: This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss. MATERIALS AND METHODS: Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites. RESULTS: Direct puncture sclerotherapy with Surgiflo or n butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively. CONCLUSION: Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon. PMID- 26549474 TI - Reconstruction of Tongue Defects With the Contralateral Nasolabial Island Flap. AB - PURPOSE: Reconstruction of tongue defects after cancer resection is challenging for reconstructive surgeons. Conventional local flaps are usually compromised in patients with suspected ipsilateral neck metastasis. To extend the application of the nasolabial flap, especially in circumstances in which a free flap is unavailable, the contralateral nasolabial island flap was used, with favorable outcomes. PATIENTS AND METHODS: Seven patients presenting with tongue carcinoma underwent surgical resection and neck dissection. Tongue defects were simultaneously reconstructed using a contralateral nasolabial island flap. Clinical outcomes, including locoregional recurrence and distant metastasis, were recorded. Subjective functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. RESULTS: All flaps survived without partial or complete necrosis. All patients survived without locoregional recurrence or distant metastasis during follow-up (6 months to 2 years). Functional outcomes were satisfactory, especially swallowing and speech functions. Donor-site morbidity was minimal and the scars were inconspicuously hidden in the nasolabial fold. CONCLUSIONS: The contralateral nasolabial island flap is technically feasible and can be an excellent option for tongue reconstruction without compromising oncologic safety. PMID- 26549475 TI - Trajectories of psychological distress after prison release: implications for mental health service need in ex-prisoners. AB - BACKGROUND: Understanding individual-level changes in mental health status after prison release is crucial to providing targeted and effective mental health care to ex-prisoners. We aimed to describe trajectories of psychological distress following prison discharge and compare these trajectories with mental health service use in the community. METHOD: The Kessler Psychological Distress Scale (K10) was administered to 1216 sentenced adult prisoners in Queensland, Australia, before prison release and approximately 1, 3 and 6 months after release. We used group-based trajectory modeling to identify K10 trajectories after release. Contact with community mental health services in the year following release was assessed via data linkage. RESULTS: We identified five trajectory groups, representing consistently low (51.1% of the cohort), consistently moderate (29.8%), high increasing (11.6%), high declining (5.5%) and consistently very high (1.9%) psychological distress. Mood disorder, anxiety disorder, history of self-harm and risky drug use were risk factors for the high increasing, very high and high declining trajectory groups. Women were over represented in the high increasing and high declining groups, but men were at higher risk of very high psychological distress. Within the high increasing and very high groups, 25% of participants accessed community mental health services in the first year post-release, for a median of 4.4 contact hours. CONCLUSIONS: For the majority of prisoners with high to very high psychological distress, distress persists after release. However, contact with mental health services in the community appears low. Further research is required to understand barriers to mental health service access among ex-prisoners. PMID- 26549476 TI - Mitochondrial response in a toddler-aged swine model following diffuse non-impact traumatic brain injury. AB - Traumatic brain injury (TBI) is an important health problem, and a leading cause of death in children worldwide. Mitochondrial dysfunction is a critical component of the secondary TBI cascades. Mitochondrial response in the pediatric brain has limited investigation, despite evidence that the developing brain's response differs from that of the adult, especially in diffuse non-impact TBI. We performed a detailed evaluation of mitochondrial bioenergetics using high resolution respirometry in a swine model of diffuse TBI (rapid non-impact rotational injury: RNR), and examined the cortex and hippocampus. A substrate uncoupler-inhibitor-titration protocol examined the role of the individual complexes as well as the uncoupled maximal respiration. Respiration per mg of tissue was also related to citrate synthase activity (CS) as an attempt to control for variability in mitochondrial content following injury. Diffuse RNR stimulated increased complex II-driven respiration relative to mitochondrial content in the hippocampus compared to shams. LEAK (State 4o) respiration increased in both regions, with decreased respiratory ratios of convergent oxidative phosphorylation through complex I and II, compared to sham animals, indicating uncoupling of oxidative phosphorylation at 24h. The study suggests that proportionately, complex I contribution to convergent mitochondrial respiration was reduced in the hippocampus after RNR, with a simultaneous increase in complex-II driven respiration. Mitochondrial respiration 24h after diffuse TBI varies by location within the brain. We concluded that significant uncoupling of oxidative phosphorylation and alterations in convergent respiration through complex I- and complex II-driven respiration reveals therapeutic opportunities for the injured at-risk pediatric brain. PMID- 26549477 TI - Biological activity of a small molecule indole analog, 1-[(1H-indol-3 yl)methylene]-2-phenylhydrazine (HMPH), in chronic inflammation. AB - A synthetic small molecule, 1-[(1H-indol-3-yl)methylene]-2-phenylhydrazine (HMPH) was conveniently synthesised by a one-step reaction, purified and characterised by chromatographic and spectroscopic methods. HMPH scavenged free radicals and inhibited lipopolysaccharide (LPS)-induced ROS generation and NO release in RAW 264.7 cells without signs of any detectable cytotoxicity. HMPH inhibited lipid peroxidation (LPO) with IC50 of 135 +/- 9 as against 58 +/- 8 MUM for alpha tocopherol. Further, HMPH (>50 MUM) significantly reduced the LPS-induced TNF alpha release in mouse peritoneal macrophages and in human peripheral blood mononuclear cells (PBMCs). HMPH did not show any visible signs of toxicity in rats up to 400 mg/kg/intraperitoneal and 2000 mg/kg/oral. HMPH at 25 and 50 mg/kg attenuated neutrophil infiltration in air-pouch lavage and bronchoalveolar lavage (BAL) in rat models. HMPH also reduced myeloperoxidase (MPO), nitrite and TNF alpha in air-pouch lavage in addition to MPO in plasma. HMPH reduced acute paw inflammation in carrageenan-induced paw-edema. HMPH consistently decreased both ipsilateral and contralateral paw inflammation, minimised the clinical scores of arthritis, prevented body weight (B.wt.) loss, attenuated serum C-reactive protein (C-RP) and rheumatoid factors (RF) in rat model of adjuvant-induced arthritis. Histopathology and radio-graphical reports show that HMPH reduced bone erosion in both ipsilateral and contralateral paw joints. Failure to inhibit COX suggests that effectiveness of HMPH in both acute and chronic inflammation is mediated by a multimodal mechanism involving modulation of immunity, attenuating TNF-alpha, protecting bone attrition and reducing oxidative stress. PMID- 26549478 TI - Resveratrol induces cell death and inhibits human herpesvirus 8 replication in primary effusion lymphoma cells. AB - Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been reported to inhibit proliferation of various cancer cells. However, the effects of resveratrol on the human herpesvirus 8 (HHV8) harboring primary effusion lymphoma (PEL) cells remains unclear. The anti-proliferation effects and possible mechanisms of resveratrol in the HHV8 harboring PEL cells were examined in this study. Results showed that resveratrol induced caspase-3 activation and the formation of acidic vacuoles in the HHV8 harboring PEL cells, indicating resveratrol treatment could cause apoptosis and autophagy in PEL cells. In addition, resveratrol treatment increased ROS generation but did not lead to HHV8 reactivation. ROS scavenger (N acetyl cysteine, NAC) could attenuate both the resveratrol induced caspase-3 activity and the formation of acidic vacuoles, but failed to attenuate resveratrol induced PEL cell death. Caspase inhibitor, autophagy inhibitors and necroptosis inhibitor could not block resveratrol induced PEL cell death. Moreover, resveratrol disrupted HHV8 latent infection, inhibited HHV8 lytic gene expression and decreased virus progeny production. Overexpression of HHV8-encoded viral FLICE inhibitory protein (vFLIP) could partially block resveratrol induced cell death in PEL cells. These data suggest that resveratrol-induced cell death in PEL cells may be mediated by disruption of HHV8 replication. Resveratrol may be a potential anti-HHV8 drug and an effective treatment for HHV8-related tumors. PMID- 26549479 TI - Catalpol downregulates vascular endothelial-cadherin expression and induces vascular hyperpermeability. AB - Catalpol, an iridiod glucoside isolated from Rehmannia glutinosa, has been reported to possess anti-inflammatory properties. However, the molecular mechanisms underlying this effect have not been fully elucidated. This study aimed to investigate the effects of catalpol on vascular permeability. Using Transwell permeability assays and measurements of trans-endothelial electrical resistance (TEER), it was demonstrated that 1 mM catalpol induces a significant increase in the permeability of the monolayers of human umbilical vein endothelial cells (HUVECs). Western blotting and immunofluorescence demonstrated that catalpol inhibits the expression of vascular endothelial (VE)-cadherin, the key component of adherens junctions, but not occludin, the major constituent of tight junctions. In addition, catalpol inhibits the ETS transcription factor ERG, a positive regulator of VE-cadherin. Knockdown of ERG expression compromised the catalpol-induced reduction of TEER in HUVECs. The present study revealed a novel effect of catalpol on vascular permeability and gave insight into the multifaceted roles of catalpol in inflammation. PMID- 26549480 TI - Relationship between patient safety climate and standard precaution adherence: a systematic review of the literature. AB - Standard precaution (SP) adherence is universally suboptimal, despite being a core component of healthcare-associated infection (HCAI) prevention and healthcare worker (HCW) safety. Emerging evidence suggests that patient safety climate (PSC) factors may improve HCW behaviours. Our aim was to examine the relationship between PSC and SP adherence by HCWs in acute care hospitals. A systematic review was conducted as guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Three electronic databases were comprehensively searched for literature published or available in English between 2000 and 2014. Seven of 888 articles identified were eligible for final inclusion in the review. Two reviewers independently assessed study quality using a validated quality tool. The seven articles were assigned quality scores ranging from 7 to 10 of 10 possible points. Five measured all aspects of SP and two solely measured needlestick and sharps handling. Three included a secondary outcome of HCW exposure; none included HCAIs. All reported a statistically significant relationship between better PSC and greater SP adherence and used data from self-report surveys including validated PSC measures or measures of management support and leadership. Although limited in number, studies were of high quality and confirmed that PSC and SP adherence were correlated, suggesting that efforts to improve PSC may enhance adherence to a core component of HCAI prevention and HCW safety. More clearly evident is the need for additional high quality research. PMID- 26549481 TI - Design of a microfluidic device to quantify dynamic intra-nuclear deformation during cell migration through confining environments. AB - The ability of cells to migrate through tissues and interstitial spaces is an essential factor during development and tissue homeostasis, immune cell mobility, and in various human diseases. Deformation of the nucleus and its associated lamina during 3-D migration is gathering increasing interest in the context of cancer metastasis, with the underlying hypothesis that a softer nucleus, resulting from reduced levels of lamin A/C, may aid tumour spreading. However, current methods to study the migration of cells in confining three dimensional (3 D) environments are limited by their imprecise control over the confinement, physiological relevance, and/or compatibility with high resolution imaging techniques. We describe the design of a polydimethylsiloxane (PDMS) microfluidic device composed of channels with precisely-defined constrictions mimicking physiological environments that enable high resolution imaging of live and fixed cells. The device promotes easy cell loading and rapid, yet long-lasting (>24 hours) chemotactic gradient formation without the need for continuous perfusion. Using this device, we obtained detailed, quantitative measurements of dynamic nuclear deformation as cells migrate through tight spaces, revealing distinct phases of nuclear translocation through the constriction, buckling of the nuclear lamina, and severe intranuclear strain. Furthermore, we found that lamin A/C deficient cells exhibited increased and more plastic nuclear deformations compared to wild-type cells but only minimal changes in nuclear volume, implying that low lamin A/C levels facilitate migration through constrictions by increasing nuclear deformability rather than compressibility. The integration of our migration devices with high resolution time-lapse imaging provides a powerful new approach to study intracellular mechanics and dynamics in a variety of physiologically-relevant applications, ranging from cancer cell invasion to immune cell recruitment. PMID- 26549482 TI - Determination of the vertical ground reaction forces acting upon individual limbs during healthy and clinical gait. AB - In gait lab, the quantification of the ground reaction forces (GRFs) acting upon individual limbs is required for dynamic analysis. However, using a single force plate, only the resultant GRF acting on both limbs is available. The aims of this study are (a) to develop an algorithm allowing a reliable detection of the front foot contact (FC) and the back foot off (FO) time events when walking on a single plate, (b) to reconstruct the vertical GRFs acting upon each limb during the double contact phase (DC) and (c) to evaluate this reconstruction on healthy and clinical gait trials. For the purpose of the study, 811 force measurements during DC were analyzed based on walking trials from 27 healthy subjects and 88 patients. FC and FO are reliably detected using a novel method based on the distance covered by the centre of pressure. The algorithm for the force reconstruction is a revised version of the approach of Davis and Cavanagh [24]. In order to assess the robustness of the algorithm, we compare the resulting GRFs with the real forces measured with individual force plates. The median of the relative error on force reconstruction is 1.8% for the healthy gait and 2.5% for the clinical gait. The reconstructed and the real GRFs during DC are strongly correlated for both healthy and clinical gait data (R(2)=0.998 and 0.991, respectively). PMID- 26549483 TI - Can a one-day practical lesson in surgical skills encourage medical students to consider a surgical career? AB - Interest in a surgical career is declining among medical students, and many more need to commit themselves to becoming surgeons to cope with this. We have therefore developed a one-day practical lesson in surgical skills to find out whether a short course such as this can make students more enthusiastic about surgery, and about subsequently pursuing a career in one of its subspecialties. Fifty-four randomly-selected medical students did a one-day practical course in the skills required for maxillofacial surgical specialties. The 4 subdivisions involved - traumatology, resection of a tumour (cancer surgery), plastic surgery (microsurgery), and cleft lip and palate surgery. All students took written tests and completed an evaluation form about their interest in a surgical career before and after training. There was a significant increase in test scores in almost all categories at the end of the course, and significantly more students were prepared to consider a surgical career or a career in maxillofacial surgery after the training. This study shows that a one-day training course in surgical skills can significantly improve medical students' surgical knowledge, and might encourage them to enter a surgical career. We recommend the integration of a short training course such as this into the medical school curriculum. Only time and further evaluation will tell whether this increased exposure to surgical techniques can be transformed into additional surgeons. PMID- 26549484 TI - Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming. AB - The mechanisms of somatic cell reprogramming have been revealed at multiple levels. However, the lack of tools to monitor different reactive oxygen species (ROS) has left their distinct signals and roles in reprogramming unknown. We hypothesized that mitochondrial flashes (mitoflashes), recently identified spontaneous bursts of mitochondrial superoxide signaling, play a role in reprogramming. Here we show that the frequency of mitoflashes transiently increases, accompanied by flash amplitude reduction, during the early stages of reprogramming. This transient activation of mitoflashes at the early stage enhances reprogramming, whereas sustained activation impairs reprogramming. The reprogramming-promoting function of mitoflashes occurs via the upregulation of Nanog expression that is associated with decreases in the methylation status of the Nanog promoter through Tet2 occupancy. Together our findings provide a previously unknown role for superoxide signaling mediated epigenetic regulation in cell fate determination. PMID- 26549486 TI - The anti-tumour activity of rLj-RGD4, an RGD toxin protein from Lampetra japonica, on human laryngeal squamous carcinoma Hep-2 cells in nude mice. AB - PURPOSE: The objective of this study is to investigate the antiproliferative activity and mechanism of integrin-binding rLj-RGD4 in a Hep-2 human laryngeal carcinoma-bearing nude mouse model. METHODS: Human laryngeal squamous carcinoma cells (Hep-2) were inoculated subcutaneously into the axilla of nude mice to generate a Hep-2 human laryngeal carcinoma-bearing nude mouse model. When the Hep 2 xenograft model was successfully established, the animals were randomly separated into five groups. Three groups were treated with different dosages of rLj-RGD4. Cisplatin was administered to the positive control group, and normal saline (NaCl) was administered to the negative control group for 3 weeks. The body weights and the survival of the nude mice were evaluated, and the volumes and weights of the solid tumours were measured. The mechanism underlying rLj-RGD4 inhibition of tumour growth in transplanted Hep-2 human laryngeal carcinoma bearing nude mice was evaluated by haematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL), measurement of intratumoural microvessel density (MVD), Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The tumour volumes and weights of the treatment groups were reduced compared with the model group, and survival times were improved by rLj-RGD4 treatment in Hep-2 human laryngeal carcinoma-bearing nude mice. The number of apoptotic Hep-2 human cells and intratumoural MVD significantly decreased after the administration of rLj-RGD4. In the xenograft tissue of animals treated with rLj-RGD4, FAK, PI3K, and Akt expression was unaltered, whereas P-FAK, P-PI3K, Bcl-2, P-Akt, and VEGF levels were down-regulated. In addition, activated caspase-3, activated caspase 9, and Bax levels were up-regulated. CONCLUSION: rLj-RGD4 exhibits potent in vivo activity and inhibits the growth of transplanted Hep-2 human laryngeal carcinoma cells in a nude mouse model. Thus, these results indicate that the recombinant RGD toxin protein rLj-RGD4 may serve as a potent clinical therapy for human laryngeal squamous carcinoma. PMID- 26549485 TI - Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance. AB - Chronic, low-grade inflammation triggered by excess intake of dietary lipids has been proposed to contribute to the pathogenesis of metabolic disorders, such as obesity, insulin resistance, type 2 diabetes, and atherosclerosis. Although considerable evidence supports a causal association between inflammation and metabolic diseases, most tests of this link have been performed in cold-stressed mice that are housed below their thermoneutral zone. We report here that thermoneutral housing of mice has a profound effect on the development of metabolic inflammation, insulin resistance, and atherosclerosis. Mice housed at thermoneutrality develop metabolic inflammation in adipose tissue and in the vasculature at an accelerated rate. Unexpectedly, this increased inflammatory response contributes to the progression of atherosclerosis but not insulin resistance. These findings not only suggest that metabolic inflammation can be uncoupled from obesity-associated insulin resistance, but also point to how thermal stress might limit our ability to faithfully model human diseases in mice. PMID- 26549487 TI - Spatial distribution of heavy metal accumulation in the sediments after dam construction. AB - The sedimentary environment has been modified in the Geum River where an estuary dam and midstream dams were constructed. Furthermore, the Geum River tributaries deliver contaminants from the wastewater of an industrial complex. However, the influence of tributaries and dams on sedimentary metal deposition has not been extensively studied. The objectives of this study are to assess metal accumulation and to investigate the source of the metals. Sediments were collected in the main channel and two tributaries on October 2013. Abnormal accumulations of fine sediments were not observed above the midstream dams. Chromium, Ni, and Zn showed higher concentrations in above the midstream dam, but their concentrations were not related to grain size. Cadmium, Cu, Pb, and Hg were much higher upstream from the first midstream dam and came from one of the major tributaries. Arsenic was the only element found at higher concentrations downstream from the last midstream dam and was likely sourced from abandoned mines and/or agricultural activity. The pollution indexes indicated deposition of all metals, except Cr and Ni, may have been affected by anthropogenic activity. With respect to long-term accumulation of the metals, accumulation of Pb, Zn, and Cu by anthropogenic input largely increased, implying accumulation of these metals has continued due to anthropogenic activity since the estuary dam was constructed. Our results suggest that changes in river flow caused by the estuary dam and anthropogenic input from tributaries sources increased the accumulation of heavy metals (e.g., Pb, Zn, Cu, and As). PMID- 26549488 TI - Telephone Assessment and Skill-Building Kit for Stroke Caregivers: A Randomized Controlled Clinical Trial. AB - BACKGROUND AND PURPOSE: There are few evidence-based programs for stroke family caregivers postdischarge. The purpose of this study was to evaluate efficacy of the Telephone Assessment and Skill-Building Kit (TASK II), a nurse-led intervention enabling caregivers to build skills based on assessment of their own needs. METHODS: A total of 254 stroke caregivers (primarily female TASK II/information, support, and referral 78.0%/78.6%; white 70.7%/72.1%; about half spouses 48.4%/46.6%) were randomized to the TASK II intervention (n=123) or to an information, support, and referral group (n=131). Both groups received 8 weekly telephone sessions, with a booster at 12 weeks. General linear models with repeated measures tested efficacy, controlling for patient hospital days and call minutes. Prespecified 8-week primary outcomes were depressive symptoms (with Patient Health Questionnaire Depressive Symptom Scale PHQ-9 >=5), life changes, and unhealthy days. RESULTS: Among caregivers with baseline PHQ-9 >=5, those randomized to the TASK II intervention had a greater reduction in depressive symptoms from baseline to 8, 24, and 52 weeks and greater improvement in life changes from baseline to 12 weeks compared with the information, support, and referral group (P<0.05); but not found for the total sample. Although not sustained at 12, 24, or 52 weeks, caregivers randomized to the TASK II intervention had a relatively greater reduction in unhealthy days from baseline to 8 weeks (P<0.05). CONCLUSIONS: The TASK II intervention reduced depressive symptoms and improved life changes for caregivers with mild to severe depressive symptoms. The TASK II intervention reduced unhealthy days for the total sample, although not sustained over the long term. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01275495. PMID- 26549489 TI - Rates and predictors of three-year mortality in older people in rural Tanzania. AB - BACKGROUND: There are few data on mortality rates in the general elderly living in sub-Saharan Africa. We aimed to detail three-year mortality rates in a population of rural community-dwelling older adults in northern Tanzania. METHODS: We performed a community-based study of 2232 people aged 70 years and over living in Hai district, Tanzania. At baseline, participants underwent clinical assessment for disability, neurological disorders, hypertension, atrial fibrillation and memory problems. At three-year follow-up mortality data were collected. Mortality rates were compared to UK estimates. RESULTS: At follow-up, data were available for 1873 subjects (83.9%). Of those, 208 (11.1%, 95% CI 9.7 12.5) had died. The age-standardised mortality rate was 10.2% (95% CI 8.8-11.6). Age-standardised mortality rates were lower than estimated for the UK (13.9%). In Cox regression analysis, greater age, higher levels of functional disability, use of a walking aid, subjective report of memory problems, being severely underweight and being normotensive were significant predictors of mortality. CONCLUSIONS: Those who survive to old age in Tanzania appear to have relatively low mortality rates. Physical and cognitive disabilities were strongly associated with mortality risk in this elderly community-dwelling population. The association between blood pressure and mortality merits further study. PMID- 26549490 TI - Systematic arthroscopic investigation of the bovine stifle joint. AB - The objective of the present study was to establish a protocol for arthroscopic exploration of the bovine stifle joint using craniomedial, caudolateral and caudomedial approaches. An anatomic and arthroscopic study using 26 cadaveric limbs from 13 non-lame adult dairy cows was performed. The craniomedial approach was created between the middle and medial patellar ligaments to investigate the cranial pouches of the stifle joint. The inter-condylar eminence, the proximal aspect of the medial femoral trochlear ridge and the lateral aspect of the lateral femoral condyle were used as starting points for systematic examination of the medial femorotibial, the femoropatellar and the lateral femorotibial joints, respectively. The observed structures were: the suprapatellar pouch, articular surfaces of the patella, femoral trochlear ridges, cruciate ligaments, menisci, and the meniscotibial ligaments. The arthroscopic portal for the caudomedial femorotibial pouch was about 6-8 cm caudal to the medial collateral ligament. The proximal and distal caudolateral femorotibial pouches were explored 3 cm and 1.5 cm caudal to the ipsilateral collateral ligament, respectively. The observed structures were the caudal aspect of femoral condyles, menisci, caudal cruciate ligament, popliteal tendon and the meniscofemoral ligament. Restricted joint size and risk of common peroneal nerve damage were the major limitations for exploration of the caudal femorotibial compartments. The study described the arthroscopic portals and normal intra-articular anatomy of the bovine stifle joint but further investigations are warranted to validate these techniques in clinical cases. PMID- 26549491 TI - At the Tip of an Iceberg: Prenatal Marijuana and Its Possible Relation to Neuropsychiatric Outcome in the Offspring. AB - Endocannabinoids regulate brain development via modulating neural proliferation, migration, and the differentiation of lineage-committed cells. In the fetal nervous system, (endo)cannabinoid-sensing receptors and the enzymatic machinery of endocannabinoid metabolism exhibit a cellular distribution map different from that in the adult, implying distinct functions. Notably, cannabinoid receptors serve as molecular targets for the psychotropic plant-derived cannabis constituent Delta(9)-tetrahydrocannainol, as well as synthetic derivatives (designer drugs). Over 180 million people use cannabis for recreational or medical purposes globally. Recreational cannabis is recognized as a niche drug for adolescents and young adults. This review combines data from human and experimental studies to show that long-term and heavy cannabis use during pregnancy can impair brain maturation and predispose the offspring to neurodevelopmental disorders. By discussing the mechanisms of cannabinoid receptor-mediated signaling events at critical stages of fetal brain development, we organize histopathologic, biochemical, molecular, and behavioral findings into a logical hypothesis predicting neuronal vulnerability to and attenuated adaptation toward environmental challenges (stress, drug exposure, medication) in children affected by in utero cannabinoid exposure. Conversely, we suggest that endocannabinoid signaling can be an appealing druggable target to dampen neuronal activity if pre-existing pathologies associate with circuit hyperexcitability. Yet, we warn that the lack of critical data from longitudinal follow-up studies precludes valid conclusions on possible delayed and adverse side effects. Overall, our conclusion weighs in on the ongoing public debate on cannabis legalization, particularly in medical contexts. PMID- 26549493 TI - Clostridium difficile infection and intestinal microbiota interactions. AB - Clostridium difficile remains the leading cause of healthcare-associated diarrhoea and outbreaks continue to occur worldwide. Aside from nosocomial C. difficile infection, the bacterium is also increasingly important as a community pathogen. Furthermore, asymptomatic carriage of C. difficile in neonates, adults and animals is also well recognised. The investigation of the gut's microbial communities, in both healthy subjects and patients suffering C. difficile infection (CDI), provides findings and information relevant for developing new successful approaches for its treatment, such as faecal microbiota transplantation, or for the prophylaxis of the infection by modification of the gut microbiota using functional foods and beverages. The analysis of all available data shows new insights into the role of intestinal microbiota in health and disease. PMID- 26549492 TI - An analysis of the influence of sex hormones on Balb/c mice infected with Plasmodium berghei. AB - Sex steroids can determine several responses in the clinical evolution of malaria. Seventy Balb-c mice were randomly distributed into 7 groups (10 mice per group): G1 to G6 corresponding to castrated females, castrated females that received estradiol cypionate, uncastrated females, castrated males, castrated males that received intramuscular testosterone decanoate and uncastrated males infected with Plasmodium berghei, and G7, the control group. The mice were evaluated with regard to survival, parasitemia, temperature, body weight, hemoglobin level (anemia) and splenic index. Castrated infected females had lower rates of survival. In the castrated male, the administration of testosterone had a negative influence on survival. There was a progressive increase in parasitemia without repercussions for survival. Castration had a significant influence on weight gain in females. Weight loss was observed in all mice, except those in groups G2 and G5, although this bore no direct relation to parasitemia. A significant and progressive decline in temperature and hemoglobin levels occurred in mice over the course of their infection, which differed from the G7 group. The weight of the spleen in relation to total body weight did not differ among the groups of infected mice, but was significantly higher than it was for the control group. PMID- 26549494 TI - "It Has No Color, It Has No Gender, It's Gender Bending": Gender and Sexuality Fluidity and Subversiveness in Drag Performance. AB - Gender identity is a key question for drag performers. Previous research has shown a lack of consensus about the subversiveness and gender fluidity of drag performers. This article examines the question: How does the relationship between performers and their audience affect the subversive nature and gender representation of drag performers in this study? Furthermore, is this relationship complicated by sexuality? This study uses ethnographic and interview methods, examining experiences of 10 drag performers. Findings indicate mutuality in the relationship between performers and audience. The recursiveness of this relationship provides a constant feedback to the performers in their effort to displace the audience's previously held notions. The performers have fluid understandings of gender and sexuality, often presenting multiple genders in and out of drag. Interactions between performers and their audience indicate their belief in gender fluidity; moreover, the drag performers themselves desire to be subversive and gender and sexually fluid. PMID- 26549496 TI - Locators versus magnetic attachment effect on peri-implant tissue health of immediate loaded two implants retaining a mandibular overdenture: a 1-year randomised trial. AB - This study aimed to evaluate peri-implant tissue health of immediate loaded two implants retaining a mandibular overdenture with either magnetic or locator attachment. Thirty two completely edentulous patients (20 males/12 females) were randomly assigned into two groups. Each patient received two implants in the canine area of the mandible using flapless surgical technique. Mandibular overdentures were immediately connected to the implants with either magnetic (group I, GI) or locator (group II, GII) attachments. Peri-implant tissue health was evaluated clinically in terms of plaque scores (PI), bleeding scores (BI), probing depth (PD), implant stability (ISQ) and interleukin-1-beta (IL-1b) concentrations in peri-implant sulcular fluid. PI, BI and PD were measured at mesial, distal, buccal and lingual surfaces of each implant. Radiographic evaluation was performed in terms of vertical (VBL) and horizontal (HBLO) alveolar bone loss. Evaluations were performed 2 weeks (T0), 6 months (T1) and 12 months (T2) after overdenture insertion. Plague scores, PD, IL-1b, VBL and HBLO increased significantly with time. ISQ decreased significantly with time. BI showed no significant differences between observation times. GI recorded significant higher PI, ISQ and IL-1b at T2 compared to GII. GII recorded significant higher VBL than GI at T2 only. For HBLO, no significant differences between groups were noted. VBL and HBLO showed a significant positive correlation with PD. Locator attachments for immediate loaded implants retaining mandibular overdentures are associated with decreased plaque accumulation, decreased implant stability, decreased interleukin-1beta concentration in peri-implant crevicular fluid and increased per-implant vertical bone loss compared to magnetic attachments after 1 year. PMID- 26549497 TI - Corrigendum. AB - Article title: "War on Drugs Redux: Welcome to the War on Doping in Sports". Author: Brian R. Alexander. Journal: Substance Use & Misuse. Bilbiometrics: Volume 49, Issue 9, Pages 1190-1193. DOI: 10.3109/10826084.2014.904119. Publisher: Informa Healthcare USA, Inc. The following parenthetical sentence found on p. 1191 was incorrect: (ASADA has previously obtained the private medical records of athletes as part of a fishing expedition looking for unusual drug prescribing.) ASADA demanded to see the medical records, but after the plan was revealed, and objections raised, the agency dropped its request before obtaining any. Therefore, the sentence should be corrected as: (ASADA has previously demanded the private medical records of athletes as part of a fishing expedition looking for unusual drug prescribing.) PMID- 26549495 TI - Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma. AB - BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment. RESULTS: In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5-8.0] mg/L) and CLD (6.1[3.6-9.6] mg/L) patients as compared to controls (2.0[1.5-2.7] mg/L, p < 0.001). sCD163 correlated with Child-Pugh and MELD scores in both HCC and CLD patients. Patients with high sCD163 levels had shorter progression-free survival (p < 0.001), but not overall survival (p = 0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts. CONCLUSIONS: We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression. PMID- 26549498 TI - Fra-1 is upregulated in lung cancer tissues and inhibits the apoptosis of lung cancer cells by the P53 signaling pathway. AB - Fos-related antigen-1 (Fra-1) is a member of the activator protein-1 transcription factor superfamily. It plays important roles in oncogenesis in various types of malignancies. Herein, we investigated the expression of Fra-1 in lung cancer tissues by qPCR, immunohistochemistry, and western blot technologies. The results showed that Fra-1 was overexpressed in the lung cancer tissues when compared with the level in the adjacent non-cancerous tissues. To explore the possible mechanism of Fra-1 in lung cancer, we elucidated the effect of Fra-1 on the apoptosis of lung cancer H460 cells, and found that the rate of cell apoptosis was decreased in the H460/Fra-1 cells compared with the H460 or H460/vector cells. Cell apoptosis is closely related with a reduction in mitochondrial membrane potential (DeltaPsim) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of Fra-1 in the lung cancer H460 cells, led to an increase in DeltaPsim and and a decrease in intracellular ROS and Ca2+ concentrations. Furthermore, we found that Fra-1 was correlated with dysregulation of the P53 signaling pathway in lung cancer tissues in vitro. At the same time, we found that Fra-1 overexpression affected the expression of MDM2 and P53 in vivo. In summary, our results suggest that Fra-1 is upregulated in lung cancer tissues and functions by affecting the P53 signaling pathway in lung cancer. PMID- 26549500 TI - Advances in temporary mechanical support for treatment of cardiogenic shock. AB - Mechanical circulatory support devices are the mainstay of treatment for severe cardiogenic shock refractory to pharmacologic therapy. Their evolution over the past few decades has been remarkable with a common theme of developing reliable, less bulky and more easily percutaneously implantable devices. The goal of this article is to review existing devices and advances in technology and provide insight into direction of further research and evolution of mechanical circulatory support devices for temporary support. PMID- 26549501 TI - Selective protected state preparation of coupled dissipative quantum emitters. AB - Inherent binary or collective interactions in ensembles of quantum emitters induce a spread in the energy and lifetime of their eigenstates. While this typically causes fast decay and dephasing, in many cases certain special entangled collective states with minimal decay can be found, which possess ideal properties for spectroscopy, precision measurements or information storage. We show that for a specific choice of laser frequency, power and geometry or a suitable configuration of control fields one can efficiently prepare these states. We demonstrate this by studying preparation schemes for strongly subradiant entangled states of a chain of dipole-dipole coupled emitters. The prepared state fidelity and its entanglement depth is further improved via spatial excitation phase engineering or tailored magnetic fields. PMID- 26549499 TI - Diversity of CRISPR-Cas immune systems and molecular machines. AB - Bacterial adaptive immunity hinges on CRISPR-Cas systems that provide DNA encoded, RNA-mediated targeting of exogenous nucleic acids. A plethora of CRISPR molecular machines occur broadly in prokaryotic genomes, with a diversity of Cas nucleases that can be repurposed for various applications. PMID- 26549502 TI - Openness to Using Non-cigarette Tobacco Products Among U.S. Young Adults. AB - INTRODUCTION: National data indicate that the prevalence of non-cigarette tobacco product use is highest among young adults; however, little is known about their openness to use these products in the future and associated risk factors. This study sought to characterize openness to using non-cigarette tobacco products and associated factors among U.S. young adults. METHODS: In 2014, National Adult Tobacco Survey data (2012-2013) were analyzed to characterize openness to using the following tobacco products among all young adults aged 18-29 years (N=5,985): cigars; electronic cigarettes ("e-cigarettes"); hookah; pipe tobacco; chew, snuff, or dip; snus; and dissolvables. Among those who were not current users of each product, multivariable logistic regression was used to examine associations between demographics, cigarette smoking status, lifetime use of other non cigarette products, perceived harm and addictiveness of smoking, and receipt of tobacco industry promotions and openness to using each product. RESULTS: Among all young adults, openness to using non-cigarette tobacco products was greatest for hookah (28.2%); e-cigarettes (25.5%); and cigars (19.1%). In multivariable analyses, which included non-current users of each product, non-current ever, current, and former smokers were more likely than never smokers to be open to using most examined products, as were men and adults aged 18-24 years. Receipt of tobacco industry promotions was associated with openness to using e-cigarettes; chew, snuff, or dip; and snus. CONCLUSIONS: There is substantial openness to trying non-cigarette tobacco products among U.S. young adults. Young adults are an important population to consider for interventions targeting non-cigarette tobacco product use. PMID- 26549503 TI - Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats. AB - This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats. PMID- 26549504 TI - Promotion of Remyelination by Sulfasalazine in a Transgenic Zebrafish Model of Demyelination. AB - Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS. PMID- 26549505 TI - Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-kappaB Signaling. AB - Rheumatoid arthritis is a chronic inflammatory disease that leads to bone and cartilage erosion. The inhibition of osteoblast differentiation by the inflammatory factor TNF-alpha is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-alpha mediated inhibition of osteoblast differentiation is required to improve therapeutic efficacy of rheumatoid arthritis. Here, we explored the potential role of rocaglamide-A, a component of Aglaia plant, in osteoblast differentiation. Rocaglamide-A prevented TNF-alpha mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells. Mechanistically, Rocaglamide-A inhibited the phosphorylation of NF-kappaB component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-kappaB responsible transcriptional activity. Oppositely, overexpression of p65 reversed rocaglamide-A's protective effects on osteoblast differentiation. Collectively, rocaglamide-A protected and stimulated osteoblast differentiation via blocking NF-kappaB pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases. PMID- 26549506 TI - Aggressive Measures to Decrease "Door to Balloon" Time and Incidence of Unnecessary Cardiac Catheterization: Potential Risks and Role of Quality Improvement. AB - OBJECTIVE: To assess the impact of an aggressive protocol to decrease the time from hospital arrival to onset of reperfusion therapy ("door to balloon [DTB] time") on the incidence of false-positive (FP) diagnosis of ST-segment elevation myocardial infarction (STEMI) and in-hospital mortality. PATIENTS AND METHODS: The study population included 1031 consecutive patients with presumed STEMI and confirmed ST-segment elevation who underwent emergent catheterization between July 1, 2008, and December 1, 2012, On July 1, 2009, we instituted an aggressive protocol to reduce DTB time. A quality improvement (QI) initiative was introduced on January 1, 2011, to maintain short DTB while improving outcomes. Outcomes were compared before and after the initiation of the DTB time protocol and similarly before and after the QI initiative. Outcomes were DTB time, the incidence of FP STEMI, and in-hospital mortality. A review of the emergency catheterization database for the 10-year period from January 1, 2001, through December 31, 2010, was performed for historical comparison. RESULTS: Of the 1031 consecutive patients with presumed STEMI who were assessed, 170 were considered to have FP STEMI. The median DTB time decreased significantly from 76 to 61 minutes with the aggressive DTB time protocol (P=.001), accompanied by an increase of FP-STEMI (7.7% vs 16.5%; P=.02). Although a nonsignificant reduction of in-hospital mortality occurred in patients with true-positive STEMI (P=.60), a significant increase in in-hospital mortality was seen in patients with FP-STEMI (P=.03). After the QI initiative, a shorter DTB time (59 minutes) was maintained while decreasing FP-STEMI in-hospital mortality. CONCLUSION: Aggressive measures to reduce DTB time were associated with an increased incidence of FP-STEMI and FP STEMI in-hospital mortality. Efforts to reduce DTB time should be monitored systematically to avoid unnecessary procedures that may delay other appropriate therapies in critically ill patients. PMID- 26549507 TI - A nationwide assessment of asthma-mental health nexus among veterans. AB - OBJECTIVE: In this study, we evaluated the association between both current and lifetime asthma to that of mental illness among veterans in the USA. METHODS: We utilized the 2005-2013 National Survey on Drug Use and Health data, a national population-based survey in the USA. Mental illness was defined as past year major depressive episode and doctor diagnosis of depression. Survey-weighted univariate and multivariable regression analyses were utilized. A total of 20,581 veterans were included in the study. RESULTS: A 4.00% and 7.50% prevalence of current and lifetime asthma were noted among veterans, respectively. A significantly higher prevalence of major depressive episode was noted among veterans with current asthma (8.23%), as compared to those without (4.68%), with a similar trend noted among those with lifetime asthma versus those without (7.84% vs. 4.58%). Doctor diagnosis of depression among veterans was higher among those with current asthma (11.83% vs. 5.86%) and lifetime asthma (10.32% vs. 5.76%), as compared to those without asthma. Upon adjusting for confounders, current asthma was significantly associated with past year major depressive episode [adjusted odds ratio (aOR) = 1.65) and depression diagnosis (aOR = 1.88). Similarly, veterans with lifetime asthma, as compared to those without, had higher odds of past year major depressive episode (aOR = 1.56) and depression diagnosis (aOR = 1.66). CONCLUSION: The asthma/mental health nexus is significant among the US veterans. Such results warrant the need for integrated care to address mental health burden among veterans with asthma. PMID- 26549508 TI - Fabrication of functional 3D hepatic tissues with polarized hepatocytes by stacking endothelial cell sheets in vitro. AB - Cell sheet stratification technology has been used for reconstituting highly functional three-dimensional (3D) hepatic tissues in vitro. Triple-layered hepatic tissues with a hepatocyte-specific polarity were fabricated by sandwiching a hepatocyte sheet (Hep sheet) between two endothelial cell (EC) sheets. The morphological and functional characteristics of the triple-layered hepatic construct (EC-Hep-EC) were evaluated and compared with those of a double layered hepatic construct with a single EC sheet (Hep-EC) and a Hep sheet only. Transmission electron microscope (TEM) observations revealed that the extracellular matrix was observed to be deposited in the space between the ECs and hepatocytes on both the upper and lower sides of the hepatocytes in the EC Hep-EC construct. Immunohistochemistry with basolateral (CD147) and apical [multidrug resistance-associated protein (MRP2)] membrane polarity markers clearly showed the recovery of in vivo-like hepatocyte polarization in the EC-Hep EC group. In addition, hepatocyte-specific functions, including albumin secretion, ammonia removal and the induction of cytochrome P450, were also highly preserved. The presented technology for stratifying multiple cell sheets was simple in operation and successfully reproduced both the heterotypic/homotypic cell-cell and cell-matrix interactions with the inherent hepatocyte configurations, thus closely mimicking the in vivo environment. The triple layered 3D hepatic constructs could therefore be valuable as a new experiment tool for drug-screening tests, an implantable tissue model for cell-based therapies and an efficient culture platform for bioartificial liver devices. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549509 TI - Urinary neopterin, a non-invasive marker of mammalian cellular immune activation, is highly stable under field conditions. AB - Studying immunity and immune function in ecology and evolution requires field studies, but there has been a dearth of non-invasive markers of immune activation available for studying large wild mammals. Recently, we analytically and biologically validated the measurement of urinary neopterin (NEO), a biomarker of cellular immune activation, in captive macaques. However, applying this to free ranging settings is complicated by issues involving sample collection, processing, storage, and transport. Here, we collected urine samples from captive macaques and undertook experiments simulating common field issues. We tested the effects on urinary NEO sample measurements following: dirt and faecal contamination; storage at room temperature; differences in processing and long term storage methods (freezing, lyophilising, blotting onto filter paper); and freeze-thaw cycles. Our results show that concentrations of urinary NEO are highly stable--they are not affected by soil or faecal contamination, can be collected on filter paper and stored for many months frozen or lyophilised with minimal effect, and are resistant to multiple 24 hr freeze-thaws. With the addition of a biocidal preservative, concentrations are even stable at room temperature for long periods. Urinary NEO is remarkably resilient, and is highly suitable for non-invasive field studies of cellular immune responses in wild large mammals. PMID- 26549510 TI - Self-reported psychosocial factors among in vitro fertilization patients interviewed alone or with the partner. AB - The purpose of this study was to compare the sociodemographic and psychosocial characteristics reported by female in vitro fertilization (IVF) patients interviewed alone or with the partner in heterosexual couples. During 12 months (2011-2012), all patients undergoing IVF or intracytoplasmic sperm injection at one public reproductive medicine unit, in Portugal, were interviewed on the day of the diagnosis of pregnancy, being recruited 221 women interviewed with the partner and 92 interviewed alone. Interviewers collected data on sociodemographic and obstetric characteristics; and anxiety, depression, social support and partner relationship were collected by self-administered questionnaires. chi2 test was used to assess the independent association between the categorical variables and being interviewed alone or with the partner. For continuous variables, mean or median differences were compared by the t-test or the Mann Whitney test, according to data distribution. No statistically significant differences were found in the self-reporting of depression, anxiety, social support and partner relationship or in sociodemographic and obstetric characteristics between women interviewed alone or with the partner. Although women interviewed alone were older and more frequently had children than women interviewed with the partner, no significant associations were observed. Thus, having a male partner present in the research setting during a self-administered questionnaire seems not to influence women's responses to psychosocial measures. Other outcomes and settings need to be evaluated to support evidence-based guidelines for research on infertility. PMID- 26549512 TI - Large-Area Metasurface Perfect Absorbers from Visible to Near-Infrared. AB - An absorptive metasurface based on film-coupled colloidal silver nanocubes is demonstrated. The metasurfaces are fabricated using simple dip-coating methods and can be deposited over large areas and on arbitrarily shaped objects. The surfaces show nearly complete absorption, good off-angle performance, and the resonance can be tuned from the visible to the near-infrared. PMID- 26549511 TI - Identifying robust communities and multi-community nodes by combining top-down and bottom-up approaches to clustering. AB - Biological functions are carried out by groups of interacting molecules, cells or tissues, known as communities. Membership in these communities may overlap when biological components are involved in multiple functions. However, traditional clustering methods detect non-overlapping communities. These detected communities may also be unstable and difficult to replicate, because traditional methods are sensitive to noise and parameter settings. These aspects of traditional clustering methods limit our ability to detect biological communities, and therefore our ability to understand biological functions. To address these limitations and detect robust overlapping biological communities, we propose an unorthodox clustering method called SpeakEasy which identifies communities using top-down and bottom-up approaches simultaneously. Specifically, nodes join communities based on their local connections, as well as global information about the network structure. This method can quantify the stability of each community, automatically identify the number of communities, and quickly cluster networks with hundreds of thousands of nodes. SpeakEasy shows top performance on synthetic clustering benchmarks and accurately identifies meaningful biological communities in a range of datasets, including: gene microarrays, protein interactions, sorted cell populations, electrophysiology and fMRI brain imaging. PMID- 26549513 TI - Daptomycin antibiotic lock therapy for hemodialysis patients with Gram-positive bloodstream infections following use of tunneled, cuffed hemodialysis catheters: retrospective single center analysis. AB - Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis patients. We assessed the efficacy of systemic daptomycin (DPT) plus DPT antibiotic lock therapy (DPT-ALT) for catheter salvage in patients with Gram positive CRBSIs. This is a retrospective study of hemodialysis patients with tunneled and cuffed hemodialysis catheters. All patients were from a single institution in Taipei and received systemic DPT plus DPT-ALT for the treatment of Gram-positive CRBSI. Successful resolution of CRBSI was implemented. Resolution of fever within 48 hours, negative result of repeated blood cultures after resolution of fever, no clinical evidence of CRBSI relapse and no need for catheter removal were measured. Fifteen hemodialysis patients received DPT-ALT for CRBSI, nine with coagulase-negative Staphylococcus (CONS), two with methicillin-resistant Staphylococcus aureus (MRSA), three with methicillin sensitive Staphylococcus aureus (MSSA) and one with polymicrobial infections. Systemic DPT plus DPT-ALT cured 11 patients (73.3%). Treatment failed in all three MRSA cases (two with MRSA and one with MRSA + Enterococcus faecalis). Retrospective design and small sample size were the limitations of this study. Systemic DPT plus DPT-ALT appears to be a promising treatment for CRBSI from CONS and MSSA, but not for MRSA CRBSI. Systemic DPT plus DPT-ALT should be considered for patients with CRBSIs caused by certain species. PMID- 26549514 TI - Application and optimization of organic-inorganic hybrid monolithic capillary electrochromatography for in vivo cefdinir determination with microdialysis. AB - In this study, an organic-inorganic hybrid monolithic capillary column was applied and optimized for the determination of cefdinir in plasma, and the electro-osmotic flow that usually hinders migration in reverse polarity became a driving force. The Sample used for pharmacokinetic research was collected by microdialysis using phosphate buffer (pH 7.4) as perfusate, and a volume of 60 MUL fluid was mixed with 140 MUL of acetonitrile. By using a silica allyldimethyldodecylammonium monolithic column (100 MUm inner diameter, 21 cm effective length and 31.2 cm total length), and a mobile phase consisting of phosphate and acetonitrile (pH 4.5, 50:50, v/v), at a voltage of 20 kV, the analytes were successfully separated with the background within 2.5 min. The detection wavelength was 214 nm. The calibration curve showed a good linearity (r(2) = 0.9994) over the concentration range of 0.2-50 MUg/mL. The proposed method showed good specificity, linearity, sensitivity, precision and recovery, and the introduction of field amplified sample stacking helped to improve the low recovery caused by microdialysis. This method was successfully applied to quantify cefdinir in rat plasma to support a pre-clinical pharmacokinetic trial. PMID- 26549515 TI - Structure prediction, expression, and antigenicity of c-terminal of GRP78. AB - Glucose-regulated protein 78 (GRP78) is a typical endoplasmic reticulum luminal chaperone having a main role in the activation of the unfolded protein response. Because of hypoxia and nutrient deprivation in the tumor microenvironment, expression of GRP78 in these cells becomes higher than the native cells, which makes it a suitable candidate for cancer targeting. Suppression of survival signals by antibody production against C-terminal domain of GR78 (CGRP) can induce apoptosis of cancer cells. The aim of this study was in silico analysis, recombinant production, and characterization of CGRP in Escherichia coli. Structural prediction of CGRP by bioinformatics tools was done and the construct containing optimized sequence was transferred to E. coli T7 shuffle. Expression was induced by isopropyl-beta-d-thiogalactoside, and recombinant protein was purified by Ni-NTA agarose resin. The content of secondary structures was obtained by circular dichroism (CD) spectrum. CGRP immunogenicity was evaluated from the immunized mouse sera. SDS-PAGE analysis showed CGRP expression in E. coli. CD spectrum also confirmed prediction of structures by bioinformatics tools. The enzyme-linked immunosorbent assay using sera from immunized mice revealed CGRP as a good immunogen. The results obtained in this study showed that the structure of truncated CGRP is very similar to its structure in the whole protein context. This protein can be used in cancer researches. PMID- 26549517 TI - The role of nursing team continuity in the treatment of very-low-birth-weight infants: findings from a pilot study. AB - AIM: To assess the association between nursing team continuity and quality of care. BACKGROUND: Research on nurse staffing and its effect on quality of care is investigated to different degrees. However, very few studies have observed whether the continuous deployment of nursing staff is associated with quality of care. METHODS: This study was conducted in two university neonatal intensive care units (NICUs). We matched nurse schedule data for the NICUs with nursing sensitive patient outcomes and quality of care, as perceived by parents. We used analysis of variance to analyse differences in nursing team continuity between NICUs and regression analyses to identify associations with the outcome measures. RESULTS: There were considerable differences between units in terms of team continuity of nursing staff. Positive associations were found between team continuity and a higher rate of non-invasive respiratory support as well as parents' perceptions of how well they knew their nurse. CONCLUSIONS: The findings show remarkable differences in staff assignment in the different NICUs. In addition to appropriate staffing levels, scheduling nursing teams continuously would appear to play a role in influencing treatment quality. IMPLICATIONS FOR NURSING MANAGEMENT: This paper emphasises the importance of carefully considered staff scheduling decisions. PMID- 26549516 TI - Parental autonomy granting and child perceived control: effects on the everyday emotional experience of anxious youth. AB - BACKGROUND: Childhood anxiety is associated with low levels of parental autonomy granting and child perceived control, elevated child emotional reactivity and deficits in child emotion regulation. In early childhood, low levels of parental autonomy granting are thought to decrease child perceived control, which in turn leads to increases in child negative emotion. Later in development, perceived control may become a more stable, trait-like characteristic that amplifies the relationship between parental autonomy granting and child negative emotion. The purpose of this study was to test mediation and moderation models linking parental autonomy granting and child perceived control with child emotional reactivity and emotion regulation in anxious youth. METHODS: Clinically anxious youth (N = 106) and their primary caregivers were assessed prior to beginning treatment. Children were administered a structured diagnostic interview and participated in a parent-child interaction task that was behaviorally coded for parental autonomy granting. Children completed an ecological momentary assessment protocol during which they reported on perceived control, emotional reactivity (anxiety and physiological arousal) and emotion regulation strategy use in response to daily negative life events. RESULTS: The relationship between parental autonomy granting and both child emotional reactivity and emotion regulation strategy use was moderated by child perceived control: the highest levels of self-reported physiological responding and the lowest levels of acceptance in response to negative events occurred in children low in perceived control with parents high in autonomy granting. Evidence for a mediational model was not found. In addition, child perceived control over negative life events was related to less anxious reactivity and greater use of both problem solving and cognitive restructuring as emotion regulation strategies. CONCLUSION: Both parental autonomy granting and child perceived control play important roles in the everyday emotional experience of clinically anxious children. PMID- 26549518 TI - Horizontally acquired oligopeptide transporters favour adaptation of Saccharomyces cerevisiae wine yeast to oenological environment. AB - In the past decade, horizontal gene transfer (HGT) has emerged as a major evolutionary process that has shaped the genome of Saccharomyces cerevisiae wine yeasts. We recently showed that a large Torulaspora microellipsoides genomic island carrying two oligopeptide transporters encoded by FOT genes increases the fitness of wine yeast during fermentation of grape must. However, the impact of these genes on the metabolic network of S. cerevisiae remained uncharacterized. Here we show that Fot-mediated peptide uptake substantially affects the glutamate node and the NADPH/NADP(+) balance, resulting in the delayed uptake of free amino acids and altered profiles of metabolites and volatile compounds. Transcriptome analysis revealed that cells using a higher amount of oligopeptides from grape must are less stressed and display substantial variation in the expression of genes in the central pathways of carbon and nitrogen metabolism, amino acid and protein biosynthesis, and the oxidative stress response. These regulations shed light on the molecular and metabolic mechanisms involved in the higher performance and fitness conferred by the HGT-acquired FOT genes, pinpointing metabolic effects that can positively affect the organoleptic balance of wines. PMID- 26549519 TI - IL-6 Inhibits Starvation-induced Autophagy via the STAT3/Bcl-2 Signaling Pathway. AB - IL-6, a pleiotropic cytokine, has been investigated for its role in regulating autophagy. Yet, its mechanism of action remains unclear. Here, we show that IL-6 exerted anti-autophagic effects on U937 cells through the STAT3 signaling pathway in vitro. The addition of IL-6 to starved U937 cells significantly activated the phosphorylation level of STAT3 (p-STAT3) at Tyr705 and reduced the protein levels of microtubule-associated protein 1 light chain 3 of type II (LC3-II) and Beclin 1. By immunoblotting, we also observed a positive correlation between the p-STAT3 level and Bcl-2 level. Furthermore, treatment with a STAT3 inhibitor, LLL12, or overexpression of a mutant form, STAT3Y705F, reversed the inhibitory effect of IL 6 on autophagy. Knockdown of Beclin 1 or Atg14 by siRNA and over-expression of Beclin 1 indicated the involvement of class III PI3K complex in IL-6-mediated inhibition of autophagy. Taken together, these data indicate that IL-6 inhibits starvation-induced autophagy and that p-STAT3 mediates the signal transduction from IL-6 to downstream proteins including Bcl-2 and Beclin1. PMID- 26549520 TI - Dissipation pattern of flubendiamide residues on capsicum fruit (Capsicum annuum L.) under field and controlled environmental conditions. AB - This investigation was undertaken to compare the dissipation pattern of flubendiamide in capsicum fruits under poly-house and open field after giving spray applications at the recommended and double doses of 48 g a.i. ha(-1) and 96 g a.i. ha(-1). Extraction and purification of capsicum fruit samples were carried out by the QuEChERS method. Residues of flubendiamide and its metabolite, des iodo flubendiamide, were analyzed by high-performance liquid chromatography photodiode array, and confirmed by liquid chromatography-mass spectrometry/mass spectrometry. Limit of quantification of the method was 0.05 mg kg(-1), and recovery of the insecticides was in the range of 89.6-104.3%, with relative standard deviation being 4.5-11.5%. The measurement uncertainty of the analytical method was in the range of 10.7-15.7%. Initial residue deposits of flubendiamide on capsicum fruits grown under poly-house conditions were (0.977 and 1.834 mg kg( 1)) higher than that grown in the field (0.665 and 1.545 mg kg(-1)). Flubendiamide residues persisted for 15 days in field-grown and for 25 days in poly-house-grown capsicum fruits. The residues were degraded with the half-lives of 4.3-4.7 and 5.6-6.6 days in field and poly-house respectively. Des-iodo flubendiamide was not detected in capsicum fruits or soil. The residues of flubendiamide degraded to below the maximum residue limit notified by Codex Alimentarius Commission (FAO/WHO) after 1 and 6 days in open field, and 3 and 10 days in poly-house. The results of the study indicated that flubendiamide applied to capsicum under controlled environmental conditions required longer pre-harvest interval to allow its residues to dissipate to the safe level. PMID- 26549521 TI - Effect of a Single Water Molecule on the Electronic Absorption by o- and p Nitrophenolate: A Shift to the Red or to the Blue? AB - Many photoactive biomolecules are anions and exhibit pipi* optical transitions but with a degree of charge transfer (CT) character determined by the local environment. The phenolate moiety is a common structural motif among biochromophores and luminophores, and nitrophenolates are good model systems because the nitro substituent allows for CT-like transitions. Here we report gas phase absorption spectra of o- and p-nitrophenolate.H2O complexes to decipher the effect of just one H2O and compare them with ab initio calculations of vertical excitation energies. The experimental band maximum is at 3.01 and 3.00 eV for ortho and para isomers, respectively, and is red-shifted by 0.10 and 0.13 eV relative to the bare ions, respectively. These shifts indicate that the transition has become more CT-like because of localization of negative charge on the phenolate oxygen, i.e., diminished delocalization of the negative excess charge. However, the transition bears less CT than that of m-nitrophenolate.H2O because this complex absorbs further to the red (2.56 eV). Our work emphasizes the importance of local perturbations: one water causes a larger shift than experienced in bulk for para isomer and almost the full shift for ortho isomer. Predicting microenvironmental effects in the boundary between CT and non-CT with high accuracy is nontrivial. However, in agreement with experiment, our calculations show a competition between the effects of electronic delocalization and electrostatic interaction with the solvent molecule. As a result, the excitation energy of ortho and para isomers is less sensitive to hydration than that of the meta isomer because donor and acceptor orbitals are only weakly coupled in the meta isomer. PMID- 26549522 TI - Clinical significance and role of LKB1 in gastric cancer. AB - Liver kinase B1 (LKB1) functions as a tumor suppressor gene, and loss in the expression of LKB1 contributes to human carcinogenesis and tumor progression. The present study investigated the association between LKB1 and gastric cancer. SGC 7901 gastric cancer cell lines and 63 patients with gastric cancer were examined in the present study, and lentivirus transfection, reverse transription quantitative polymerase chain reaction and flow cytometric analyses were performed. By examining the expression of LKB1 using immunohistochemical analyses, the present study found that the expression of LKB1 was reduced in the gastric cancer tissues, and restoration of the expression of LKB1 reduced tumor cell viability, migration rate and the expression of CD44, induced cell cycle arrest at the G2 phase of the cell cycle, and increased the sensitivity of the gastric cancer cells to anticancer drugs. LKB1 protein is a tumor-suppressor in gastric cancer and may be potentially be developed as a novel gene therapy target in the treatment of gastric cancer. PMID- 26549523 TI - An EGFR/Src-dependent beta4 integrin/FAK complex contributes to malignancy of breast cancer. AB - beta4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients, and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between beta4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of beta4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of beta4 integrin, which, in turn, recruits FAK to beta4 integrin and leads to FAK activation and signaling. Upon disruption of the beta4 integrin/FAK complex, tumorigenesis and metastasis in triple negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of beta4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent beta4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer. PMID- 26549524 TI - Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica, Reduces LRRC8A Expression and Volume-Sensitive Release of Organic Osmolytes in Human Lung Epithelial Cancer Cells. AB - We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 ug/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 -> 200 mOsm) by 60%. C75 (20 ug/mL, 24 h), a gamma-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 ug/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to gamma-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4 ) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 MUM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells. PMID- 26549525 TI - Cryogenic abnormal thermal expansion properties of carbon-doped La(Fe,Si)13 compounds. AB - Recently, La(Fe,Si)13-based compounds have attracted much attention due to their isotropic and tunable abnormal thermal expansion (ATE) properties as well as bright prospects for practical applications. In this research, we have prepared cubic NaZn13-type carbon-doped La(Fe,Si)13 compounds by the arc-melting method, and their ATE and magnetic properties were investigated by means of variable temperature X-ray diffraction, strain gauge and the physical property measurement system (PPMS). The experimental results indicate that both micro and macro negative thermal expansion (NTE) behaviors gradually weaken with the increase of interstitial carbon atoms. Moreover, the temperature region with the most remarkable NTE properties has been broadened and near zero thermal expansion (NZTE) behavior occurs in the bulk carbon-doped La(Fe,Si)13 compounds. PMID- 26549526 TI - Development and psychometric evaluation of a questionnaire on nurses' clinical competence eye care in intensive care unit patients. AB - BACKGROUND: Given the high prevalence of eye disorders in intensive care units, evaluating critical care nurses' competence in providing standard eye care is a matter of utmost importance. However, to the best of our knowledge, there is no valid questionnaire for measuring nurses' competence to undertake eye care. AIMS: The aim of this study was to develop and evaluate the psychometric properties of a questionnaire on nurses' clinical competence in providing eye care to patients hospitalized in intensive care units. DESIGN: This was a psychometric study. METHODS: We initially performed a literature review and developed a 38-item questionnaire consisting of knowledge, attitude and practice domains. We invited a panel of experts and a group of critical care nurses to assess the content and face validity of the questionnaire. Thereafter, we evaluated its construct validity by using the exploratory factor analysis and the known-groups comparison technique. Moreover, the test-retest and the internal consistency evaluation techniques were used for assessing the reliability of the questionnaire. RESULTS: Totally, 35 items remained in the final version of the questionnaire. Based on the results of the exploratory factor analysis, we categorized the items of the questionnaire into three factors. The Cronbach's alpha for the attitude and the practice domains as well as the Kuder-Richardson 20 for the knowledge domain showed satisfactory internal consistency. The Cronbach's alpha for the whole questionnaire also was 0.83. CONCLUSION: The results of this study suggest that the nurses' clinical competence in eye care questionnaire has a good factor structure and an acceptable reliability. RELEVANCE TO CLINICAL PRACTICE: A complication of sedation and coma is that some patients are unable to maintain effective eyelid closure. These patients present a higher risk of eye complications. Development of tools for evaluating nurses' competence in providing standard eye care is a fundamental prerequisite for improving the quality of eye care. PMID- 26549527 TI - Nuclear dynamics in the metastable phase of the solid acid caesium hydrogen sulfate. AB - High-resolution spectroscopic measurements using thermal and epithermal neutrons and first-principles calculations within the framework of density-functional theory are used to investigate the nuclear dynamics of light and heavy species in the metastable phase of caesium hydrogen sulfate. Within the generalised-gradient approximation, extensive calculations show that both 'standard' and 'hard' formulations of the Perdew-Burke-Ernzerhof functional supplemented by Tkatchenko Scheffler dispersion corrections provide an excellent description of the known structure, underlying vibrational density of states, and nuclear momentum distributions measured at 10 and 300 K. Encouraged by the agreement between experiment and computational predictions, we provide a quantitative appraisal of the quantum contributions to nuclear motions in this solid acid. From this analysis, we find that only the heavier caesium atoms reach the classical limit at room temperature. Contrary to naive expectation, sulfur exhibits a more pronounced quantum character relative to classical predictions than the lighter oxygen atom. We interpret this hitherto unexplored nuclear quantum effect as arising from the tighter binding environment of this species in this technologically relevant material. PMID- 26549528 TI - Oral insulin delivery systems using chitosan-based formulation: a review. AB - INTRODUCTION: There are several hurdles to oral insulin delivery (OID): mainly, enzymatic proteolysis, gastric degradation, and an absorption barrier. Researchers have been attempting to overcome these natural barriers through chitosan-based insulin formulations. AREAS COVERED: In this paper, the authors review OID formulations to elucidate their techniques and evaluate their performance through a set of defined parameters and suggest overall outlooks and future directions. This review covers 86 articles and reveals that most oral insulin formulations were obtained through poly-electrolytic complexation or chemical modification techniques. The in-vitro results reported by the articles are mapped into a '30x70 performance window' to distinguish the best OID formulations. The review shows that most formulations were effective in addressing the gastric and enzymatic barriers but were not as effective in overcoming the absorption barrier of the gastrointestinal tract. EXPERT OPINION: Oral insulin delivery has been a topic of immense research with most efforts dedicated to developing a formidable insulin formulation that overcomes gastrointestinal tract barriers. While most OID formulations perform better under experimental conditions, their performance in in-vivo studies is not as effective. Thus, to make oral insulin delivery a reality, special attention is needed toward improving the in-vivo insulin absorption through the gut. PMID- 26549529 TI - Bulk-Induced 1/f Noise at the Surface of Three-Dimensional Topological Insulators. AB - Slow intrinsic fluctuations of resistance, also known as the flicker noise or 1/f noise, in the surface transport of strong topological insulators (TIs) is a poorly understood phenomenon. Here, we have systematically explored the 1/f-noise in field-effect transistors (FET) of mechanically exfoliated Bi1.6Sb0.4Te2Se TI films when transport occurs predominantly via the surface states. We find that the slow kinetics of the charge disorder within the bulk of the TI induces mobility fluctuations at the surface, providing a new source of intrinsic 1/f noise that is unique to bulk TI systems. At small channel thickness, the noise magnitude can be extremely small, corresponding to the phenomenological Hooge parameter gammaH as low as ~10(-4), but it increases rapidly when channel thickness exceeds ~1 MUm. From the temperature (T)-dependence of noise, which displayed sharp peaks at characteristic values of T, we identified generation recombination processes from interband transitions within the TI bulk as the dominant source of the mobility fluctuations in surface transport. Our experiment not only establishes an intrinsic microscopic origin of noise in TI surface channels, but also reveals a unique spectroscopic information on the impurity bands that can be useful in bulk TI systems in general. PMID- 26549530 TI - Sequential In Vitro Cyclization by Cytochrome P450 Enzymes of Glycopeptide Antibiotic Precursors Bearing the X-Domain from Nonribosomal Peptide Biosynthesis. AB - The biosynthesis of the glycopeptide antibiotics, which include vancomycin and teicoplanin, relies on the interplay between the peptide-producing non-ribosomal peptide synthetase (NRPS) and Cytochrome P450 enzymes (P450s) that catalyze side chain crosslinking of the peptide. We demonstrate that sequential in vitro P450 catalyzed cyclization of peptide substrates is enabled by the use of an NRPS peptide carrier protein (PCP)-X di-domain as a P450 recruitment platform. This study reveals that whilst the precursor peptide sequence influences the installation of the second crosslink by the P450 OxyAtei , activity is not restricted to the native teicoplanin peptide. Initial peptide cyclization is possible with teicoplanin and vancomycin OxyB homologues, and the latter displays excellent activity with all substrate combinations tested. By using non-natural X domain substrates, bicyclization of hexapeptides was also shown, which demonstrates the utility of this method for the cyclization of varied peptide substrates in vitro. PMID- 26549531 TI - Insulin decreases autophagy and leads to cartilage degradation. AB - OBJECTIVE: Autophagy, a key homeostasis mechanism, is defective in Osteoarthritis (OA) and Type 2 Diabetes (T2D). T2D has been proposed as a risk factor for OA. We hypothesized that diabetes impairs articular cartilage integrity by decreasing autophagy. Our objective was to investigate the effects of high glucose and insulin, characteristics of T2D, on cartilage homeostasis. METHODS: Immortalized human chondrocytes (TC28a2) and primary human chondrocytes (HC) were cultured in 25 mM or 0 mM glucose and treated with insulin (10, 100, 500 nM) for 2, 6 or 24 h. Activity of LC3-II, Akt and rpS6 was evaluated by Western blotting (WB). Human cartilage explants were cultivated with 25 mM glucose and insulin (100,1000 nM) for 24 h to evaluate histopathology. MMP-13 and IL-1beta expression was determined by immunohistochemistry and WB. Effects of Rapamycin (10 MUM) were analyzed by WB. LC3 and rpS6 expression was determined by WB in chondrocytes from Healthy, Non Diabetic-OA and Diabetic-OA patients. RESULTS: Insulin downregulates autophagy by reducing LC3 II expression and increasing Akt and rpS6 phosphorylation. Loss of proteoglycans and increased MMP-13 and IL-1beta expression was observed after insulin treatment. Autophagy activation by rapamycin reversed insulin effects. Importantly, chondrocytes from diabetic-OA patients showed decreased LC3 and increased p-rpS6 expression compared to Healthy and Non-Diabetic OA patients. CONCLUSIONS: These results suggest that decreased autophagy might be a mechanism by which diabetes influences cartilage degradation. Pharmacological activation of autophagy may be an effective therapeutic approach to prevent T2D-induced cartilage damage. PMID- 26549532 TI - Multiwalled Carbon Nanotubes at the Interface of Pickering Emulsions. AB - Carbon nanotubes exhibit very unique properties in biphasic systems. Their interparticle attraction leads to reduced droplet coalescence rates and corresponding improvements in emulsion stability. Here we use covalent and noncovalent techniques to modify the hydrophilicity of multiwalled carbon nanotubes (MWCNTs) and study their resulting behavior at an oil-water interface. By using both paraffin wax/water and dodecane/water systems, the thickness of the layer of MWNTs at the interface and resulting emulsion stability are shown to vary significantly with the approach used to modify the MWNTs. Increased hydrophilicity of the MWNTs shifts the emulsions from water-in-oil to oil-in water. The stability of the emulsion is found to correlate with the thickness of nanotubes populating the oil-water interface and relative strength of the carbon nanotube network. The addition of a surfactant decreases the thickness of nanotubes at the interface and enhances the overall interfacial area stabilized at the expense of increased droplet coalescence rates. To the best of our knowledge, this is the first time the interfacial thickness of modified carbon nanotubes has been quantified and correlated to emulsion stability. PMID- 26549533 TI - The first prognostic model for stroke and death in patients with systolic heart failure. AB - BACKGROUND: Patients with systolic heart failure (HF) are at increased risk of both ischemic stroke and death. Currently, no risk scores are available to identify HF patients at high risk of stroke or death. The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial studied 2305 HF patients, in sinus rhythm, followed for up to 6 years (3.5+/-1.5 years). This trial showed no overall difference in those treated with warfarin vs aspirin with regard to death or stroke. The present study develops the first prognostic model to identify patients at higher risk of stroke or death based on their overall risk profile. METHODS AND RESULTS: A scoring algorithm using 8 readily obtainable clinical characteristics as predictors, age, gender, hemoglobin, blood urea nitrogen, ejection fraction, diastolic blood pressure, diabetes status, and prior stroke or transient ischemic attack (C-index=0.65, 95% CI: 0.613-0.681), was developed. It was validated internally using a bootstrap method. In predicting 1-year survival for death alone, our 8-predictor model had an AUC of 0.63 (95% CI: 0.579-0.678) while the 14-predictor Seattle model had an AUC of 0.72. The Seattle model did not report stroke. CONCLUSIONS: This novel prognostic model predicts the overall risk of ischemic stroke or death for HF patients. This model compares favorably for death with the Seattle model and has the added utility of including stroke as an endpoint. Use of this model will help identify those patients in need of more intensive monitoring and therapy and may help identify appropriate populations for trials of new therapies. CLINICAL TRIAL REGISTRATION: http://www.Clinicatrials.govNCT00041938. PMID- 26549535 TI - Ultraporous nanocrystalline TiO2-based films: synthesis, patterning and application as anti-reflective, self-cleaning, superhydrophilic coatings. AB - Crack-free, anatase-based optical coatings with a refractive index down to 1.27, a porosity up to 80 vol%, and a tunable thickness up to 1.5 MUm were fabricated. The extraordinary stability of the porosity upon thermally induced crystallisation and template removal was attributed to the combined effects of the presence of 10% molar silica in the inorganic phase, a flash treatment at 500 degrees C, and the use of templates with different dimensions ranging from a few nanometers to 50 nm. The hierarchical porous system was directly patterned by UV lithography and used as multifunctional anti-reflective, self-cleaning coatings. PMID- 26549534 TI - Exploration and practice of methods and processes of evidence-based rapid review on peer review of WHO EML application. AB - OBJECTIVE: After 38 years of development, the procedure of selection and evaluation of the World Health Organization Essential Medicine List (WHO EML) is increasingly scientific and formal. However, peer review for the applications of World Health Organization Essential Medicine List is always required in a short period. It is necessary to build up a set of methods and processes for rapid review. METHOD: We identified the process of evidenced-based rapid review on WHO EML application for peer reviews according to 11 items which were required during reporting of the peer review results of the proposals. RESULTS: The most important items for the rapid review of World Health Organization Essential Medicine List peer reviewers are (1) to confirm the requirements and identify the purposes; (2) to establish the research questions and translate the questions into the 'Participants, Interventions, Comparators, Outcomes, Study design' (PICOS) format; (3) to search and screen available evidence, for which high-level evidence is preferred, such as systematic reviews or meta-analyses, health technology assessment, clinical guidelines; (4) to extract data, where we extract primary information based on the purposes; (5) to synthesize data by qualitative methods, assess the quality of evidence, and compare the results; (6) to provide the answers to the applications, quality of evidences and strength of recommendations. CONCLUSIONS: Our study established a set of methods and processes for the rapid review of World Health Organization Essential Medicine List peer review, and our findings were used to guide the reviewers to fulfill the 19(th) World Health Organization Essential Medicine List peer review. The methods and processes were feasible and met the necessary requirements in terms of time and quality. Continuous improvement and evaluation in practice are warranted. PMID- 26549536 TI - Pitfall in the Diagnosis of Fructose-1,6-Bisphosphatase Deficiency: Difficulty in Detecting Glycerol-3-Phosphate with Solvent Extraction in Urinary GC/MS Analysis. AB - Fructose-1,6-bisphosphatase (FBPase), an enzyme involved in gluconeogenesis, catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. FBPase deficiency is an autosomal recessive inherited disorder, characterized by episodic attacks of hypoglycemia, ketosis, and lactic acidosis during fasting. In general, urinary organic acid analysis using gas chromatography-mass spectrometry (GC/MS) is very useful for the diagnosis of FBPase deficiency, because the appearance of glycerol or glycerol-3-phosphate in the urine is characteristic of this disease. Here, we report a case of FBPase deficiency in a girl with a history of several severe lactic acidosis events, both as a neonate and after the age of 12 months. The patient was identified as a compound heterozygote with two mutations in the FBPase 1 gene: c.841G>A (p.Glu281Lys) and c.960_961insG (p.Ser321fs). The c.841G>A is a newly identified pathogenic mutation. An abnormal level of glycerol-3-phosphate was not detected in the conventional urinary organic acid analysis using GC/MS after solvent extraction. This method, which is a widely used diagnostic standard, could not detect increased levels of glycerol or glycerol-3-phosphate in the patient's urine, which was sampled during the episode. However, glycerol and glycerol-3 phosphate were detected in the same sample, when it was analyzed using GC/MS with the urease pretreatment non-extraction method. Patients with FBPase deficiency have good glycemic control after correct treatment. Therefore, accurate and early diagnosis is essential for a good prognosis. Accordingly, when a patient presents with hypoglycemia and lactic acidosis, it is important to select the appropriate method of urinalysis for organic acids by GC/MS. PMID- 26549538 TI - Dynamics of the layer-by-layer assembly of a poly(acrylic acid)-lanthanide complex colloid and poly(diallyldimethyl ammonium). AB - Poly(acrylic acid) (PAA) and lanthanide (Ln) ions, such as Ce(3+), Eu(3+), and Tb(3+), were prepared as dispersed complex colloidal particles through three different protocols with rigorous control of the pH value and mixing ratio. The negatively charged PAA-Ln complex particles were layer-by-layer (LbL) assembled with positively charged poly(diallyldimethyl ammonium) (PDDA) to prepare a thin film. The film thickness growth is much quicker than PDDA/PAA film. Due to the incorporation of Ln(3+) ions, the film exhibits fluorescence. During LbL assembly, PDDA-PAA association based on electrostatic force and PAA-Ce association based on coordination are in competition, which leads to the LbL assembly of PDDA and PAA-Ln complex colloidal particles being a complicated dynamic process. PMID- 26549537 TI - 3D matrix-based cell cultures: Automated analysis of tumor cell survival and proliferation. AB - Three-dimensional ex vivo cell cultures mimic physiological in vivo growth conditions thereby significantly contributing to our understanding of tumor cell growth and survival, therapy resistance and identification of novel potent cancer targets. In the present study, we describe advanced three-dimensional cell culture methodology for investigating cellular survival and proliferation in human carcinoma cells after cancer therapy including molecular therapeutics. Single cells are embedded into laminin-rich extracellular matrix and can be treated with cytotoxic drugs, ionizing or UV radiation or any other substance of interest when consolidated and approximating in vivo morphology. Subsequently, cells are allowed to grow for automated determination of clonogenic survival (colony number) or proliferation (colony size). The entire protocol of 3D cell plating takes ~1 h working time and pursues for ~7 days before evaluation. This newly developed method broadens the spectrum of exploration of malignant tumors and other diseases and enables the obtainment of more reliable data on cancer treatment efficacy. PMID- 26549539 TI - Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection. AB - Single-molecule surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Many conventional substrates have a broad distribution of SERS enhancements, which compromise reproducibility and result in slow response times for single-molecule detection. Here we report a smart plasmonic sensor that can reversibly trap a single molecule at hotspots for rapid single-molecule detection. The sensor was fabricated through electrostatic self-assembly of gold nanoparticles onto a gold/silica-coated silicon substrate, producing a high yield of uniformly distributed hotspots on the surface. The hotspots were isolated with a monolayer of a thermoresponsive polymer (poly(N-isopropylacrylamide)), which act as gates for molecular trapping at the hotspots. The sensor shows not only a good SERS reproducibility but also a capability to repetitively trap and release molecules for single-molecular sensing. The single-molecule sensitivity is experimentally verified using SERS spectral blinking and bianalyte methods. PMID- 26549540 TI - Regulation of tumorigenic Wnt signaling by cyclooxygenase-2, 5-lipoxygenase and their pharmacological inhibitors: A basis for novel drugs targeting cancer cells? AB - Canonical Wnt signaling is a highly conserved pathway with a prominent role in embryogenic development, adult tissue homeostasis, cell polarization, stem cell biology, cell differentiation, and proliferation. Furthermore, canonical Wnt signaling is of pivotal importance in the pathogenesis of a number of cancer types and crucially affects tumor initiation, cancer cell proliferation, cancer cell apoptosis, and metastasis. Reports over the last decade have provided strong evidence for a pathophysiological role of Wnt signaling in non-malignant classical inflammatory and neurodegenerative diseases. Although, several agents suppressing the Wnt pathway at different levels have been identified, the development of clinically relevant Wnt-inhibiting agents remains challenging due to selectivity and toxicity issues. Several studies have shown that long-term administration of non-steroidal anti-inflammatory drugs protects against colon cancer and potentially other tumor types by interfering both with the COX and the Wnt pathway. Our own studies have shown that non-steroidal anti-inflammatory drugs suppress Wnt signaling by targeting the pro-inflammatory enzyme 5 lipoxygenase which is the key enzyme pathophysiologically involved in the synthesis of leukotrienes. Furthermore, we found a direct link between the 5 lipoxygenase and Wnt signaling pathways, which is essential for the maintenance of leukemic stem cells. Accordingly, genetic and pharmacological inhibition of 5 lipoxygenase led to an impairment of Wnt-dependent acute and chronic myeloid leukemic stem cells. We believe that 5-lipoxygenase inhibitors might represent a novel type of Wnt inhibitor activating a potentially naturally occurring novel mechanism of suppression of Wnt signaling that is non-toxic, at least in mice, and is potentially well tolerated in patients. PMID- 26549541 TI - Metabotropic glutamate receptors as targets for new antipsychotic drugs: Historical perspective and critical comparative assessment. AB - In this review, we aim to present, discuss and clarify our current understanding regarding the prediction of possible antipsychotic effects of metabotropic glutamate (mGlu) receptor ligands. The number of preclinical trials clearly indicates, that this group of compounds constitutes an excellent alternative to presently used antipsychotic therapy, being effective not only to positive, but also negative and cognitive symptoms of schizophrenia. Although the results of clinical trials that were performed for the group of mGlu2/3 agonists were not so enthusiastic as in animal studies, they still showed that mGlu ligands do not induced variety of side effects typical for presently used antipsychotics, and were generally well tolerated. The lack of satisfactory effectiveness towards schizophrenia symptoms of mGlu2/3 activators in humans could be a result of variety of uncontrolled factors and unidentified biomarkers different for each schizophrenia patient, that should be taken into consideration in the future set of clinical trials. The subject is still open for further research, and the novel classes of mGlu5 or mGlu2/3 agonists/PAMs were recently introduced, including the large group of compounds from the third group of mGlu receptors, especially of mGlu4 subtype. Finally, more precise treatment based on simultaneous administration of minimal doses of the ligands for two or more receptors, seems to be promising in the context of symptoms-specific schizophrenia treatment. PMID- 26549542 TI - Treatment of Sarcopenic Dysphagia with Rehabilitation and Nutritional Support: A Comprehensive Approach. PMID- 26549543 TI - Editorial: Metabolic Diseases: Drugs and Mitochondrial Targets. PMID- 26549544 TI - Influence of Vanin-1 and Catalytic Products in Liver During Normal and Oxidative Stress Conditions. AB - In liver, cysteamine in all probability represents a "low-capacity, high affinity" scavenger of ROS. The available body of evidence suggests that reduced cysteamine and oxidized cystamine exist in equilibrium and that this ratio acts as an active redox sensor within the cell much like GSH. During normal liver homeostasis cysteamine's antioxidant properties are evident. Highly metabolic and/or pro-oxidative conditions, such as in mice treated with peroxisome proliferators, shift this equilibrium to favor the oxidized form. Under these conditions, cystamine is likely able to inactivate proteins involved in energy biogenesis through cysteaminylation of critical Cys residues as has been shown in vitro. This would allow cystamine to function as a "metabolic brake" to prevent the formation of additional ROS. In vivo, subcellular localization, pH, reducing capacity, FMO status and metabolic rate are all probable factors in determining the cysteamine:cystamine ratio. The availability of free cysteamine is also regulated by hydrolysis of pantetheine by pantetheinase. This cleavage results in the formation of pantothenic acid, a precursor to Coenzyme A which is prominently involved with lipid metabolism and energy production by the beta -oxidation pathway and TCA cycle, respectively. Expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. The use of Vnn1 knockout mice has provided clear evidence that Vnn1 modulates redox and immune pathways In vivo, both of which appear at least partially due to a loss of cysteamine/cystamine. Immunologically, Vnn1 expression may influence cell signaling indirectly through maintenance of disulfide bonds or directly by interaction of pantetheinase on the cell surface. Cysteamine treatment has been used clinically as an antidote to APAP poisoning and in animal models against hepatotoxicants including APAP, galactosamine and CCl4. Protection in animal models occurs even when administered up to 12 hours following intoxication, suggesting that protection is the result of effects that occur downstream of bioactivation and covalent binding of reactive metabolites to target cellular macromolecules. Currently, the downstream influences of Vnn1 expression and cysteamine at endogenous concentrations remain largely unknown. Vnn1 knockout mice represent a valuable tool available to researchers investigating these events. Future studies in the field are needed to elucidate the precise mechanisms by which pantetheinase and/or cysteamine impact immune cell recruitment, cell signaling and survival, though it is clear that these factors have far reaching implications in the fields of immunology and toxicology. PMID- 26549545 TI - Comparison between linear and proportional hazard models for the analysis of age at first lambing in the Ripollesa breed. AB - Age at first lambing (AFL) plays a key role on the reproductive performance of sheep flocks, although there are no genetic selection programs accounting for this trait in the sheep industry. This could be due to the non-Gaussian distribution pattern of AFL data, which must be properly accounted for by the analytical model. In this manuscript, two different parameterizations were implemented to analyze AFL in the Ripollesa sheep breed, that is, the skew Gaussian mixed linear model (sGML) and the piecewise Weibull proportional hazards model (PWPH). Data were available from 10 235 ewes born between 1972 and 2013 in 14 purebred Ripollesa flocks located in the north-east region of Spain. On average, ewes gave their first lambing short after their first year and a half of life (590.9 days), and within-flock averages ranged between 523.4 days and 696.6 days. Model fit was compared using the deviance information criterion (DIC; the smaller the DIC statistic, the better the model fit). Model sGML was clearly penalized (DIC=200 059), whereas model PWPH provided smaller estimates and reached the minimum DIC when one cut point was added to the initial Weibull model (DIC=132 545). The pure Weibull baseline and parameterizations with two or more cut points were discarded due to larger DIC estimates (>134 200). The only systematic effect influencing AFL was the season of birth, where summer- and fall born ewes showed a remarkable shortening of their AFL, whereas neither birth type nor birth weight had a relevant impact on this reproductive trait. On the other hand, heritability on the original scale derived from model PWPH was high, with a model estimate place at 0.114 and its highest posterior density region ranging from 0.079 and 0.143. As conclusion, Gaussian-related mixed linear models should be avoided when analyzing AFL, whereas model PWPH must be viewed as better alternative with superior goodness of fit; moreover, the additive genetic background underlying this reproductive trait supports its inclusion into current genetic selection programs given its economic importance. PMID- 26549546 TI - Ratiometric and colorimetric near-infrared sensors for multi-channel detection of cyanide ion and their application to measure beta-glucosidase. AB - A near-infrared sensor for cyanide ion (CN(-)) was developed via internal charge transfer (ICT). This sensor can selectively detect CN(-) either through dual ratiometric fluorescence (logarithm of I414/I564 and I803/I564) or under various absorption (356 and 440 nm) and emission (414, 564 and 803 nm) channels. Especially, the proposed method can be employed to measure beta-glucosidase by detecting CN(-) traces in commercial amygdalin samples. PMID- 26549547 TI - Post-Coital Urinary Incontinence: Lessons Learned about Pelvic Neuronal Pathways. PMID- 26549548 TI - Should Geometric Mean Calculation of Differential Renal Function be Used When Evaluating Children with Moderate to Severe Hydronephrosis? PMID- 26549550 TI - Effects of CDC42 on the proliferation and invasion of gastric cancer cells. AB - Cell division cycle 42 (CDC42), which is a member of the Rho GTPase family, has been reported to regulate the metastasis of various human cancer cells; however, the role of CDC42 in gastric cancer (GC) remains unclear. The present study aimed to investigate the effects of CDC42 on the proliferation, migration and invasion of GC. Furthermore, the molecular mechanisms underlying the effects of CDC42 on GC were explored. The expression levels of CDC42 in the AGS and SGC7901 human GC cell lines were reduced by RNA interference. Knockdown of CDC42 significantly inhibited the proliferation of AGS and SGC7901 cells, and it was suggested that this inhibitory process may be due to cell cycle arrest at G1/S phase and downregulation of cyclin A, cyclin D1, cyclin E and proliferating cell nuclear antigen. Furthermore, knockdown of CDC42 markedly inhibited the migration and invasion of GC cells, and suppressed the expression of matrix metalloproteinase 9. These results indicated that CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of GC, and it may be considered a potential therapeutic target in GC. PMID- 26549552 TI - WILLINGNESS TO PAY FOR LUNG CANCER TREATMENT: PATIENT VERSUS GENERAL PUBLIC VALUES-ERRATUM. AB - Owing to an editorial error, in the article by Thongprasert et al. (1) in the August 2015 issue of International Journal of Technical Assessment in Health Care, Bruce Crawford was incorrectly listed as the corresponding author. The corresponding author is Unchalee Permsuwan. PMID- 26549551 TI - Efficacy of a Brief Intervention to Reduce Substance Use and Human Immunodeficiency Virus Infection Risk Among Latino Youth. AB - PURPOSE: Familias Unidas is an efficacious and effective family-based intervention for preventing and reducing substance use and unsafe sexual behaviors among Latino youth. To facilitate its dissemination, Familias Unidas was shortened from a 12-week intervention to a 6-week intervention and evaluated. We hypothesized that brief Familias Unidas would be efficacious in reducing substance use and unsafe sexual behaviors relative to a comparison condition. METHODS: We randomized 160 ninth-grade Latino adolescents and their families to brief Familias Unidas or a community practice control condition. Adolescents were surveyed at baseline and 6, 12, and 24 months after baseline. RESULTS: At 24 months, youth randomized to brief Familias Unidas had a significantly lower sexual initiation rate (34.0%) relative to control (55.0%), p = .02. Brief Familias Unidas also increased positive parenting. Moderation analyses revealed that brief Familias Unidas was significantly associated with decreased substance use initiation among girls (30.4% vs. 64.0%, respectively; p = .02), but not boys (28.0% vs. 26.7%, respectively; p = .91). Brief Familias Unidas was also significantly associated with reduced unsafe sex among adolescents aged 15 years or less (p < .001), but not among older adolescents (p = .37). Moderating effects were also found for family-level variables. CONCLUSIONS: Brief Familias Unidas was efficacious in reducing sex initiation and improving positive parenting. Moderation analyses suggested that brief Familias Unidas was efficacious in reducing substance use initiation and unsafe sex for certain Hispanic adolescent subgroups, highlighting the importance of conducting moderation analyses, and of targeting interventions for specific subgroups. PMID- 26549553 TI - Erratum to: design of chemical space networks using a Tanimoto similarity variant based upon maximum common substructures. PMID- 26549554 TI - Physiological responses to Tai Chi in stable patients with COPD. AB - We compared the physiological work, judged by oxygen uptake, esophageal pressure swing and diaphragm electromyography, elicited by Tai Chi compared with that elicited by constant rate treadmill walking at 60% of maximal load in eleven patients with COPD (Mean FEV1 61% predicted, FEV1/FVC 47%). Dynamic hyperinflation was assessed by inspiratory capacity and twitch quadriceps tension (TwQ) elicited by supramaximal magnetic stimulation of the femoral nerve was also measured before and after both exercises. The EMGdi and esophageal pressure at the end of exercise were similar for both treadmill exercise and Tai Chi (0.109+/ 0.047 mV vs 0.118+/-0.061 mV for EMGdi and 22.3+/-7.1 cmH2O vs 21.9+/-8.1 cmH2O for esophageal pressure). Moreover the mean values of oxygen uptake during Tai Chi and treadmill exercise did not differ significantly: 11.3 ml/kg/min (51.1% of maximal oxygen uptake derived from incremental exercise) and 13.4 ml/kg/min (52.5%) respectively, p>0.05. Respiratory rate during Tai Chi was significantly lower than that during treadmill exercise. Both Tai Chi and treadmill exercise elicited a fall in IC at end exercise, indicating dynamic hyperinflation, but this was statistically significant only after treadmill exercise. TwQ decreased significantly after Tai Chi but not after treadmill. We conclude that Tai Chi constitutes a physiologically similar stimulus to treadmill exercise and may therefore be an acceptable modality for pulmonary rehabilitation which may be culturally more acceptable in some parts of the world. PMID- 26549555 TI - Diaphragm muscle weakness and increased UCP-3 gene expression following acute hypoxic stress in the mouse. AB - The effects of acute hypoxia on the diaphragm are largely unknown despite the clinical relevance to respiratory conditions such as acute respiratory distress syndrome and ventilator-induced lung injury. Adult male C57BL6/J mice were exposed to 1, 4 or 8h of hypoxia (FiO2=0.10) or normoxia. Ventilation was assessed by whole-body plethysmography during gas exposures. Diaphragm isotonic contractile parameters were assessed ex vivo. Diaphragm gene expression was determined using qRT-PCR. Acute hypoxic stress resulted in significant diaphragm muscle weakness. Gene expression data revealed that hypoxia results in temporal changes in various transcriptional genes regulating mitochondrial function and a time-dependent progressive increase in the expression of the mitochondrial uncoupling protein 3 (UCP-3) with concomitant changes in genes encoding sarcoplasmic reticulum calcium release proteins. Altered gene expression and muscle weakness are likely due to direct effects of hypoxic stress per se, and not related to increased diaphragm muscle activity, as there was no persistent change in ventilation during hypoxic exposure. These findings suggest a potentially critical role for hypoxia in diaphragm muscle remodeling in acute respiratory-related disorders. PMID- 26549556 TI - Sequential change in physicochemical properties of LDL during oxidative modification. AB - Oxidized LDL is thought to be a highly atherogenic lipoprotein. Structural background of this pathogenesis, however, has not yet been well defined. Physicochemical characterization of this lipoprotein is still controversial, which therefore makes it difficult to take a mechanistic approach to its atherogenicity. We thus conducted investigation of time-dependent changes in chemical compositions and alternation of physical properties of LDL in detail during its oxidation induced by human embryonic endothelial cells and copper ions. The oxidation caused hydrolysis of glycerolipids being demonstrated as decrease of triglyceride and choline-phospholipid and increase of lysophosphatidylcholine. Fragmentation of apoB was also induced while over-all protein components stayed with the particles. The density of the particles continuously shifted to higher fractions for all the particles to reach d >= 1.044 after 10h incubation. The average diameter of LDL, however, decreased from 28.1 nm to 25.6 nm by 5h and increased to 27.1 nm towards 20 h incubation with the increase of discoid particles. These dynamic changes can be interpreted by losing fatty acyl group from the core lipid components perhaps due to oxidative degradation and by increase of surface lysophosphatidylcholine to cause remodeling of the particles. PMID- 26549557 TI - Collective motion of mammalian cell cohorts in 3D. AB - Collective cell migration is ubiquitous in biology, from development to cancer; it occurs in complex systems comprised of heterogeneous cell types, signals and matrices, and requires large scale regulation in space and time. Understanding how cells achieve organized collective motility is crucial to addressing cellular and tissue function and disease progression. While current two-dimensional model systems recapitulate the dynamic properties of collective cell migration, quantitative three-dimensional equivalent model systems have proved elusive. To establish such a model system, we study cell collectives by tracking individuals within cell cohorts embedded in three dimensional collagen scaffolding. We develop a custom algorithm to quantify the temporal and spatial heterogeneity of motion in cell cohorts during motility events. In the absence of external driving agents, we show that these cohorts rotate in short bursts, <2 hours, and translate for up to 6 hours. We observe, track, and analyze three dimensional motion of cell cohorts composed of 3-31 cells, and pave a path toward understanding cell collectives in 3D as a complex emergent system. PMID- 26549558 TI - Is Single-Dose Etomidate Induction Safe in Emergency Intubation of Critically Ill Patients? PMID- 26549559 TI - HMGB1: A critical mediator for oxidized-low density lipoproteins induced atherosclerosis. PMID- 26549560 TI - Ticagrelor therapy in patients with advanced conduction disease: Is it really safe? PMID- 26549561 TI - Pheochromocytoma and takotsubo. PMID- 26549562 TI - Possibilities and limitations for co-transplantation of cardiac atrial appendage stem cells and mesenchymal stem cells for myocardial repair. PMID- 26549563 TI - Could familial hypercholesterolemia oppose the diabetogenic effect of statin? Comments on a new SAFEHEART study. PMID- 26549564 TI - Pacemaker indication in first-degree AV block patients: Factors beyond the PR interval/HR slope. PMID- 26549565 TI - Survival after primary percutaneous coronary intervention. PMID- 26549566 TI - Fault diagnosis and fault-tolerant finite control set-model predictive control of a multiphase voltage-source inverter supplying BLDC motor. AB - Due to its fault tolerance, a multiphase brushless direct current (BLDC) motor can meet high reliability demand for application in electric vehicles. The voltage-source inverter (VSI) supplying the motor is subjected to open circuit faults. Therefore, it is necessary to design a fault-tolerant (FT) control algorithm with an embedded fault diagnosis (FD) block. In this paper, finite control set-model predictive control (FCS-MPC) is developed to implement the fault-tolerant control algorithm of a five-phase BLDC motor. The developed control method is fast, simple, and flexible. A FD method based on available information from the control block is proposed; this method is simple, robust to common transients in motor and able to localize multiple open circuit faults. The proposed FD and FT control algorithm are embedded in a five-phase BLDC motor drive. In order to validate the theory presented, simulation and experimental results are conducted on a five-phase two-level VSI supplying a five-phase BLDC motor. PMID- 26549567 TI - Tuning the Model Predictive Control of a Crude Distillation Unit. AB - Tuning the parameters of the Model Predictive Control (MPC) of an industrial Crude Distillation Unit (CDU) is considered here. A realistic scenario is depicted where the inputs of the CDU system have optimizing targets, which are provided by the Real Time Optimization layer of the control structure. It is considered the nominal case, in which both the CDU model and the MPC model are the same. The process outputs are controlled inside zones instead of at fixed set points. Then, the tuning procedure has to define the weights that penalize the output error with respect to the control zone, the weights that penalize the deviation of the inputs from their targets, as well as the weights that penalize the input moves. A tuning approach based on multi-objective optimization is proposed and applied to the MPC of the CDU system. The performance of the controller tuned with the proposed approach is compared through simulation with the results of an existing approach also based on multi-objective optimization. The simulation results are similar, but the proposed approach has a computational load significantly lower than the existing method. The tuning effort is also much lower than in the conventional practical approaches that are usually based on ad hoc procedures. PMID- 26549568 TI - Exploring midwives' perception of confidence around facilitating water birth in Western Australia: A qualitative descriptive study. AB - OBJECTIVE: the option of labouring and/or birthing immersed in warm water has become widely available throughout hospitals in the United Kingdom and Europe over the last two decades. The practice, which also occurs in New Zealand and interstate in Australia, has until recently only been available in Western Australia for women birthing at home with a small publically funded Community Midwifery Program. Despite its popularity and acceptance elsewhere, birth in water has only recently become an option for women attending some public health services in Western Australia. The Clinical Guidelines developed for the local context that support water birth require that the midwives be confident and competent to care for these women. The issue of competency can be addressed with relative ease by maternity care providers; however confidence is rather more difficult to teach, foster and attain. Clinical confidence is an integral element of clinical judgement and promotes patient safety and comfort. For this reason confident midwives are an essential requirement to support the option of water birth in Western Australia. The aim of this study was to capture midwives' perceptions of becoming and being confident in conducting water birth in addition to factors perceived to inhibit and facilitate the development of that confidence. DESIGN: a modified grounded theory methodology with thematic analysis. SETTINGS: four public maternity services offering the option of water birth in the Perth metropolitan area. PARTICIPANTS: registered midwives employed at one of the four publicly funded maternity services that offered the option of water birth between June 2011 and June 2013. Sixteen midwives were interviewed on a one to one basis. An additional 10 midwives participated in a focus group interview. FINDINGS: three main categories emerged from the data analysis: what came before the journey, becoming confident - the journey and staying confident. Each contained between three and five subcategories. Together they depicted how midwives describe the journey to becoming confident to support women who have chosen the option to water birth and how they are able to retain that confidence once achieved. IMPLICATIONS FOR PRACTICE: three key implications emerged from this study, the first was that students and graduate midwives could benefit from the opportunity to work in midwifery led maternity settings that support normal physiological child birth and that accessing such practical placements should be encouraged. Secondly, maternity services would benefit from learning opportunities directed specifically at experienced midwives addressing their particular requirements. Finally, midwives are the custodians of normal physiological birth, attendance at educational days with a focus on supporting this primary role should be mandatory, to inform midwives on current evidence found to support normal birth which includes options such as water birth. PMID- 26549570 TI - PBOV1 correlates with progression of ovarian cancer and inhibits proliferation of ovarian cancer cells. AB - Prostate and breast cancer overexpressed 1 (PBOV1) is significantly upregulated in prostate, breast and bladder cancer, while its expression status in ovarian cancer and its clinical significance are unclear. We examined the expression levels of PBOV1 mRNA and protein in ovarian cancer cell lines and primary tissues using real-time PCR and western blotting. Immunohistochemistry was employed to analyze PBOV1 expression in 17 normal ovaries, 13 cystadenoma tissues, 14 borderline tumor tissues, and 165 clinicopathologically characterized ovarian cancers. There was negative PBOV1 expression in the 17 normal ovarian epithelial tissues. Compared to the normal ovarian epithelial cells, PBOV1 mRNA and protein were overexpressed in ovarian cancer cell lines. There was high PBOV1 protein expression in the ovarian cancer tissues from 59 of the 165 (35.8%) patients; PBOV1 expression was weak in 106 (64.2%) patients. Notably, there were significant negative associations between high PBOV1 expression and ascending histological grade, late pT/pN/pM, and International Federation of Gynecology and Obstetrics (FIGO) stage (P<0.05). Patients with high PBOV1 expression had longer overall survival; patients with low PBOV1 expression had shorter survival. Multivariate analysis revealed that PBOV1 upregulation is an independent prognostic indicator for ovarian cancer and might serve as a tumor-suppressor gene. Furthermore, PBOV1 overexpression inhibited ovarian cancer cell proliferation and tumorigenesis in vitro and in a tumor transplantation nude mouse model. In conclusion, our results suggest that PBOV1 may play an important role in suppressing ovarian cancer proliferation and carcinogenesis. PBOV1 may be a novel and useful prognostic marker and potential target for treating human ovarian cancer. PMID- 26549569 TI - LKB1 Regulates Cerebellar Development by Controlling Sonic Hedgehog-mediated Granule Cell Precursor Proliferation and Granule Cell Migration. AB - The Liver Kinase B1 (LKB1) gene plays crucial roles in cell differentiation, proliferation and the establishment of cell polarity. We created LKB1 conditional knockout mice (LKB1(Atoh1) CKO) to investigate the function of LKB1 in cerebellar development. The LKB1(Atoh1) CKO mice displayed motor dysfunction. In the LKB1(Atoh1) CKO cerebellum, the overall structure had a larger volume and more lobules. LKB1 inactivation led to an increased proliferation of granule cell precursors (GCPs), aberrant granule cell migration and overproduction of unipolar brush cells. To investigate the mechanism underlying the abnormal foliation, we examined sonic hedgehog signalling (Shh) by testing its transcriptional mediators, the Gli proteins, which regulate the GCPs proliferation and cerebellar foliation during cerebellar development. The expression levels of Gli genes were significantly increased in the mutant cerebellum. In vitro assays showed that the proliferation of cultured GCPs from mutant cerebellum significantly increased, whereas the proliferation of mutant GCPs significantly decreased in the presence of a Shh inhibitor GDC-0049. Thus, LKB1 deficiency in the LKB1(Atoh1) CKO mice enhanced Shh signalling, leading to the excessive GCP proliferation and the formation of extra lobules. We proposed that LKB1 regulates cerebellar development by controlling GCPs proliferation through Shh signalling during cerebellar development. PMID- 26549571 TI - Is It Dating Violence or Just "Drunken Behavior"? Judgments of Intimate Partner Violence When the Perpetrator Is Under the Influence of Alcohol. AB - BACKGROUND: Previous research has shown a strong bias for laypersons to believe alcohol use and aggression to go hand-in-hand (see Quigley & Leonard, 2006 ). Furthermore, research has shown that alcohol use can be seen as a mitigating circumstance for aggression, resulting in a reduction of blame and accountability (Bullock, 2002 ; Katz & Arias, 2001 ; Tryggvesson, 2004 ). OBJECTIVES: The present study investigated observers' judgments of intimate partner violence (IPV) when the perpetrator was under the influence of alcohol. We hypothesized that participants would view violent behavior as more common and less abusive if they thought the perpetrator was under the influence of alcohol. METHODS: College students (n = 79) viewed a video depicting an increasingly abusive interaction between college-age dating partners (see Witte & Kendra, 2010 ) and half of the participants were lead to believe that the perpetrator was drinking alcohol prior to the interaction. Participants rated the videotaped vignette at four timepoints to assess the degree to which they believed the interaction was normal/common and abusive. RESULTS: Observers judged the abusive behavior as more common and less abusive when alcohol was involved, but only for psychologically abusive behaviors and moderately severe physically abusive behaviors. CONCLUSIONS/IMPORTANCE: The results of this study provide support for the notion that direct observers of IPV judge moderately abusive behavior as more common and less abusive when alcohol is involved. With this, theories concerning alcohol expectancies and interpretations of interpersonal violence can be more readily applied to real-life scenarios, such as in the validity of eye-witness testimony. PMID- 26549572 TI - Cancer treatment in determination of hearing loss. AB - INTRODUCTION: Chemotherapy and radiotherapy in oncology have repercussions in hearing health, and can damage structures of the inner ear. These repercussions usually, result in a bilateral and irreversible hearing loss. OBJECTIVE: To identify sensorineural hearing loss cases with complaints of tinnitus and difficulty in speech understanding and investigate their relationship with the types of chemotherapy and radiotherapy the patients received. METHODS: Cross sectional, clinical, observational, analytical, historical cohort study of 58 subjects treated in a public hospital in the state of Sergipe, diagnosed with neoplasia. The subjects were submitted to anamnesis, conventional pure tone audiometry, and speech recognition threshold. RESULTS: Of the 116 ears, 25.9% presented sensorioneural hearing loss characterized by changes in high frequencies. There was a positive correlation between hearing loss and the association of chemotherapy and radiotherapy (p=0.035; R=0.196). The auditory complaint analysis shows that most of the subjects had tinnitus and speech understanding difficulty, even with a normal auditory threshold. CONCLUSIONS: Cancer treatment causes hearing loss, associated with the administration of chemotherapy and radiotherapy. Cyclophosphamide increased the risk of causing hearing loss. Complaints of tinnitus and speech understanding difficulty were observed. PMID- 26549573 TI - Improved predictive ability of the Montreal Cognitive Assessment for diagnosing dementia in a community-based study. AB - INTRODUCTION: We compared the predictive ability of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to diagnose dementia in a community-based study. METHODS: A total of 276 people aged 60 years or older were enrolled. All of the participants were administered face-to-face interview questionnaires and MoCA and MMSE examinations. The receiver operating characteristic curve method and area under curve were performed to assess the predictive ability for diagnosing dementia. RESULTS: The 276 participants had a mean age of 67.9 +/- 6.1 years and mean education duration of 11.4 +/- 4.0 years. In general, the MoCA yielded higher AUCs (0.891) with favorable sensitivity (78 %) and excellent specificity (94 %) compared with the MMSE in differentiating the participants with and without dementia in either the total sample or all subgroups. CONCLUSION: Our study determined a higher predictive ability in the MoCA than in the MMSE for diagnosing dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in a community-based sample with a broader range of education level. PMID- 26549574 TI - Short-term follow-up systems for positive newborn screens in the Washington Metropolitan Area and the United States. AB - For most inherited metabolic disorders on newborn screening (NBS) panels, prompt, expert confirmation and treatment are critical to optimize clinical outcomes for children with inherited metabolic diseases (IMD). In the Washington Metropolitan Area (WMA), 3 different short-term follow-up (STFU) systems exist for linking infants with positive newborn screens for IMD to appropriate specialty care. We diagrammed the STFU systems for the District of Columbia, Maryland and Virginia and calculated clinically relevant intervals of time between NBS collection and diagnosis/treatment initiation. We also surveyed representatives from 48 other state NBS programs to classify the STFU systems in the rest of the country. We found that in the WMA the STFU system that did not include the IMD specialist at the same time as the primary care provider (PCP) was associated with a longer median collection-to-specialist contact interval for true positive NBS for critical diagnoses (p=0.013). Nationally, 25% of state NBS programs report having a STFU system that does not include the IMD specialist at the same time as the PCP. In conclusion, there is variability among the STFU systems employed by NBS programs in the US which may lead to delays in diagnosis confirmation and treatment. National standards for STFU systems that include early involvement of an IMD specialist for all presumed positive NBS results may decrease the collection-to-specialist contact interval which could improve clinical outcomes in children with IMD. PMID- 26549575 TI - Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy. AB - Coenzyme A (CoA) is a ubiquitous cofactor involved in numerous essential biochemical transformations, and along with its thioesters is a key regulator of intermediary metabolism. Pantothenate (vitamin B5) phosphorylation by pantothenate kinase (PanK) is thought to control the rate of CoA production. Pantothenate kinase associated neurodegeneration is a hereditary disease that arises from mutations that inactivate the human PANK2 gene. Aryl phosphoramidate phosphopantothenate derivatives were prepared to test the feasibility of using phosphopantothenate replacement therapy to bypass the genetic deficiency in the Pank1(-/-) mouse model. The efficacies of candidate compounds were first compared by measuring the ability to increase CoA levels in Pank1(-/-) mouse embryo fibroblasts. Administration of selected candidate compounds to Pank1(-/-) mice corrected their deficiency in hepatic CoA. The PanK bypass was confirmed by the incorporation of intact phosphopantothenate into CoA using triple-isotopically labeled compound. These results provide strong support for PanK as a master regulator of intracellular CoA and illustrate the feasibility of employing PanK bypass therapy to restore CoA levels in genetically deficient mice. PMID- 26549576 TI - A discrete-choice experiment to quantify patient preferences for frequency of glucagon-like peptide-1 receptor agonist injections in the treatment of type 2 diabetes. AB - OBJECTIVE: Understanding patients' preferences for attributes of injectable antihyperglycemic regimens may improve patient satisfaction and medication adherence. Our objective was to quantify the preferences of patients with type 2 diabetes mellitus (T2DM) for reducing the frequency of glucagon-like peptide-1 receptor agonist injections from once daily to once weekly. METHODS: A total of 643 respondents with a self-reported physician diagnosis of type 2 diabetes completed a web-based discrete-choice experiment survey. The sample included four prespecified subgroups: currently using exenatide once weekly (n = 150), liraglutide once daily (n = 153), insulin (but not exenatide once weekly or liraglutide) (n = 156), and no injectable treatment (n = 184). Device attributes included type of injection device, needle size and pain, injection frequency, refrigeration, and injection-site reactions. Random-parameters logit was used to estimate the relative impact of device attributes on treatment choice for each subgroup. RESULTS: In all subgroups, changing injection frequency from daily to weekly (independent of the effect of injection frequency on preferences for other attributes) was the most important predictor of treatment choice. Switching from a longer and thicker needle to a shorter and thinner needle and eliminating injection-site reactions were also statistically significant predictors of device choice (P < 0.05). Exenatide once weekly users and those not currently using injections were more likely to choose a treatment with characteristics similar to exenatide once weekly. CONCLUSIONS: The treatment attribute most important to patients choosing among hypothetical injectable treatments for T2DM was injection frequency: patients preferred weekly over daily injections. LIMITATIONS: The primary limitations of this study are that it included only a limited number of attributes that may not reflect the full complexity of patient choices, diagnosis was self-reported, and patients were recruited from an Internet panel and may not be representative of the T2DM patient population. PMID- 26549577 TI - Microparticulate beta-glucan vaccine conjugates phagocytized by dendritic cells activate both naive CD4 and CD8 T cells in vitro. AB - Microparticulate beta-glucan (MG) conjugated to vaccine antigen has been shown to serve as an effective adjuvant in vivo. To further study antigen presentation by MG:vaccine conjugates, bone marrow-derived dendritic cells (BMDC) were treated with MG conjugated to ovalbumin (OVA), then interacted with splenocytes from DO11.10 transgenic mice expressing an OVA peptide-specific T cell receptor. BMDC treated with MG:OVA induced significantly higher numbers of activated (CD25+CD69+) OVA-specific CD4+ T cells than BMDC treated with OVA alone. BMDC treated with MG:OVA upregulated CD86 and CD40 expression as well as MG alone, indicating that conjugation of OVA does not alter the immunostimulatory capacity of MG. Activation of CD8+ OVA-specific OT-1 cells showed that MG:OVA is also capable of enhancing cross-presentation by BMDC to CD8+ cytotoxic T cells. These results show that MG acts as an adjuvant to enhance antigen presentation by dendritic cells to naive, antigen-specific CD4 and CD8 T cells. PMID- 26549578 TI - Peripheral, functional and postural asymmetries related to the preferred chewing side in adults with natural dentition. AB - The aim of this cross-sectional study was to determine the preferred chewing side and whether chewing side preference is related to peripheral, functional or postural lateral preferences. One hundred and forty-six adults with natural dentition performed three masticatory assays, each consisting of five trials of chewing three pieces of silicon placed into a latex bag for 20 cycles, either freestyle or unilaterally on the right- or left-hand side. Occlusal contact area in the intercuspal position, maximum bite force, masticatory performance and cycle duration were measured and the lateral asymmetry of these variables was calculated. Laterality tests were performed to determine handedness, footedness, earedness and eyedness as functional preferences, and hand-clasping, arm-folding and leg-crossing as postural lateral preferences. The preferred chewing side was determined using three different methods: assessment of the first chewing cycle for each trial, calculation of the asymmetry index from all cycles and application of a visual analogue scale. Bivariate relationship and multiple linear regression analyses were performed. Among unilateral chewers, 77% of them preferred the right side for chewing. The factors most closely related to the preferred chewing side were asymmetry of bite force, asymmetry of masticatory performance and earedness, which explained up to 16% of the variance. Although several functional or postural lateral preferences seem to be related to the preferred chewing side, peripheral factors such as asymmetry of bite force and of masticatory performance are the most closely related to the preferred chewing side in adults with natural dentition. PMID- 26549579 TI - A quantitative review of the postmortem evidence for decreased cortical N-methyl D-aspartate receptor expression levels in schizophrenia: How can we link molecular abnormalities to mismatch negativity deficits? AB - Evidence suggests that anomalous mismatch negativity (MMN) in schizophrenia is related to glutamatergic abnormalities, possibly involving N-methyl-D-aspartate (NMDA) receptors. Decreased cortical expressions of NMDA receptor subunits have been observed in schizophrenia, though not consistently. To aid with integration and interpretation of previous work, we performed a meta-analysis of effect sizes of mRNA or protein levels of the obligatory NR1 subunit in prefrontal cortex from people with schizophrenia. In schizophrenia compared to unaffected controls the pooled effect size was -0.64 (95% confidence interval: -1.08 to -0.20) for NR1 mRNA reduction and -0.44 (95% confidence interval: -0.80 to -0.07) for NR1 protein reduction. These results represent the first step to a deeper understanding of the region-specific, cell-specific, and stage-specific NMDA receptor hypofunction in schizophrenia, which could be linked to mismatch negativity deficits via transgenic and pharmacological animal models. PMID- 26549580 TI - New and Improved Techniques for the Study of Pathogenic Fungi. AB - Fungal pathogens pose serious threats to human, plant, and ecosystem health. Improved diagnostics and antifungal strategies are therefore urgently required. Here, we review recent developments in online bioinformatic tools and associated interactive data archives, which enable sophisticated comparative genomics and functional analysis of fungal pathogens in silico. Additionally, we highlight cutting-edge experimental techniques, including conditional expression systems, recyclable markers, RNA interference, genome editing, compound screens, infection models, and robotic automation, which are promising to revolutionize the study of both human and plant pathogenic fungi. These novel techniques will allow vital knowledge gaps to be addressed with regard to the evolution of virulence, host pathogen interactions and antifungal drug therapies in both the clinic and agriculture. This, in turn, will enable delivery of improved diagnosis and durable disease-control strategies. PMID- 26549581 TI - The Mineralosphere Concept: Mineralogical Control of the Distribution and Function of Mineral-associated Bacterial Communities. AB - Soil is composed of a mosaic of different rocks and minerals, usually considered as an inert substrata for microbial colonization. However, recent findings suggest that minerals, in soils and elsewhere, favour the development of specific microbial communities according to their mineralogy, nutritive content, and weatherability. Based upon recent studies, we highlight how bacterial communities are distributed on the surface of, and in close proximity to, minerals. We also consider the potential role of the mineral-associated bacterial communities in mineral weathering and nutrient cycling in soils, with a specific focus on nutrient-poor and acidic forest ecosystems. We propose to define this microbial habitat as the mineralosphere, where key drivers of the microbial communities are the physicochemical properties of the minerals. PMID- 26549582 TI - Aim, Load, Fire: The Type VI Secretion System, a Bacterial Nanoweapon. AB - Bacteria utilise specialised protein secretion systems to interact with host organisms, competitor bacteria, and the environment. The Type VI secretion system (T6SS) is a versatile weapon deployed by many bacterial species to target either host cells or rival bacteria. The widespread occurrence and significance of the T6SS is becoming increasingly appreciated, as is its intriguing mode of action. The T6SS delivers multiple, diverse effector proteins directly into target cells using a dynamic 'firing' mechanism related to the action of contractile bacteriophage tails. Here, we summarise the contribution of recent findings to our developing picture of how the T6SS assembles and fires, how it is loaded with different types of effectors, and how it can be aimed towards an incoming assault. PMID- 26549583 TI - An in-depth examination into pharmacy technician worklife through an organizational behavior framework. AB - BACKGROUND: Pharmacy technicians are a vital part of the health care workforce. Little is known about perceptions of their own work environment that would engender more effective recruitment, retention, and management strategies by pharmacists and employers. OBJECTIVES: The purpose of this study was to gain a greater understanding of certified pharmacy technician worklife. Specific objectives included the identification of themes of worklife phenomena to assist with the development of appropriate responses by other pharmacy stakeholders and to ascertain the contribution of various factors engendering or discouraging career commitment of pharmacy technicians. METHODS: Semi-structured in-depth interviews were carried out with a convenience sample of pharmacy technicians in one U.S. state, who varied by their work settings and level of experience. The interview guide and corresponding participant responses were framed from around an organizational cultural basis rooted in organizational behavior theory. Notes from the interviews were analyzed thematically using directed content analysis. RESULTS: Four primary themes emerged, including: career impetus, job responsibilities, quality of work life, and equitable partnership. The data revealed pharmacy technicians' need for self-actualization and recognition of the value they bring to the organization. The participants identified primary responsibilities that contribute to their sense of worth and those that if not managed adequately potentially detract from their well-being and effectiveness. Findings in regard to rate of pay corroborate previous work on wages as both an intrinsic and extrinsic motivator. Pharmacy technicians seek equity among each other (their peers) and in a mutually beneficial relationship with their employing organization. CONCLUSIONS: This study provides the impetus for interventions and further study that should serve to enhance pharmacy technician effectiveness, quality of work life, and longevity in an emerging profession. PMID- 26549584 TI - Shock assisted ionization injection in laser-plasma accelerators. AB - Ionization injection is a simple and efficient method to trap an electron beam in a laser plasma accelerator. Yet, because of a long injection length, this injection technique leads generally to the production of large energy spread electron beams. Here, we propose to use a shock front transition to localize the injection. Experimental results show that the energy spread can be reduced down to 10 MeV and that the beam energy can be tuned by varying the position of the shock. This simple technique leads to very stable and reliable injection even for modest laser energy. It should therefore become a unique tool for the development of laser-plasma accelerators. PMID- 26549585 TI - Still trying to pick the best asparaginase preparation. PMID- 26549587 TI - Chemotherapy improves survival in appendiceal cancer. PMID- 26549586 TI - Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05 001): a randomised, open-label phase 3 trial. AB - BACKGROUND: l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05 001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia. METHODS: DFCI 05-001 enrolled patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia from 11 consortium sites in the USA and Canada. Patients were assigned to an initial risk group on the basis of their baseline characteristics and then underwent 32 days of induction therapy. Those who achieved complete remission after induction therapy were assigned to a final risk group and were eligible to participate in a randomised comparison of intravenous PEG-asparaginase (15 doses of 2500 IU/m(2) every 2 weeks) or intramuscular native E colil-asparaginase (30 doses of 25 000 IU/m(2) weekly), beginning at week 7 after study entry. Randomisation (1:1) was unmasked, and was done by a statistician-generated allocation sequence using a permuted blocks algorithm (block size of 4), stratified by final risk group. The primary endpoint of the randomised comparison was the overall frequency of asparaginase-related toxicities (defined as allergy, pancreatitis, and thrombotic or bleeding complications). Predefined secondary endpoints were disease-free survival, serum asparaginase activity, and quality of life during therapy as assessed by PedsQL surveys. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00400946. FINDINGS: Between April 22, 2005, and Feb 12, 2010, 551 eligible patients were enrolled. 526 patients achieved complete remission after induction, of whom 463 were randomly assigned to receive intramuscular native E colil asparaginase (n=231) or intravenous PEG-asparaginase (n=232). The two treatment groups did not differ significantly in the overall frequency of asparaginase related toxicities (65 [28%] of 232 patients in the intravenous PEG-asparaginase group vs 59 [26%] of 231 patients in the intramuscular native E colil asparaginase group, p=0.60), or in the individual frequency of allergy (p=0.36), pancreatitis (p=0.55), or thrombotic or bleeding complications (p=0.26). Median follow-up was 6.0 years (IQR 5.0-7.1). 5-year disease-free survival was 90% (95% CI 86-94) for patients assigned to intravenous PEG-asparaginase and 89% (85-93) for those assigned to intramuscular native E colil-asparaginase (p=0.58). The median nadir serum asparaginase activity was significantly higher in patients who received intravenous PEG-asparaginase than in those who received intramuscular native E colil-asparaginase. Significantly more anxiety was reported by both patients and parent-proxy in the intramuscular native E colil-asparaginase group than in the intravenous PEG-asparaginase group. Scores for other domains were similar between the groups. The most common grade 3 or worse adverse events were bacterial or fungal infections (47 [20%] of 232 in the intravenous PEG asparaginase group vs 51 [22%] of 231 patients in the intramuscular E colil asparaginase group) and asparaginase-related allergic reactions (14 [6%] vs 6 [3%]). INTERPRETATION: Intravenous PEG-asparaginase was not more toxic than, was similarly efficacious to, and was associated with decreased anxiety compared with intramuscular native E colil-asparaginase, supporting its use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukaemia. FUNDING: National Cancer Institute and Enzon Pharmaceuticals. PMID- 26549588 TI - Sorafenib and novel multikinase inhibitors in AML. PMID- 26549590 TI - Low BMI linked to worse colorectal cancer outcomes. PMID- 26549591 TI - Personalising the treatment of prostate cancer. PMID- 26549589 TI - Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. AB - BACKGROUND: Preclinical data and results from non-randomised trials suggest that the multikinase inhibitor sorafenib might be an effective drug for the treatment of acute myeloid leukaemia. We investigated the efficacy and tolerability of sorafenib versus placebo in addition to standard chemotherapy in patients with acute myeloid leukaemia aged 60 years or younger. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was done at 25 sites in Germany. We enrolled patients aged 18-60 years with newly diagnosed, previously untreated acute myeloid leukaemia who had a WHO clinical performance score 0-2, adequate renal and liver function, no cardiac comorbidities, and no recent trauma or operation. Patients were randomly assigned (1:1) to receive two cycles of induction therapy with daunorubicin (60 mg/m(2) on days 3-5) plus cytarabine (100 mg/m(2) on days 1-7), followed by three cycles of high-dose cytarabine consolidation therapy (3 g/m(2) twice daily on days 1, 3, and 5) plus either sorafenib (400 mg twice daily) or placebo on days 10-19 of induction cycles 1 and 2, from day 8 of each consolidation, and as maintenance for 12 months. Allogeneic stem-cell transplantation was scheduled for all intermediate-risk patients with a sibling donor and for all high-risk patients with a matched donor in first remission. Computer-generated randomisation was done in blocks. The primary endpoint was event-free survival, with an event defined as either primary treatment failure or relapse or death, assessed in all randomised patients who received at least one dose of study treatment. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00893373, and the EU Clinical Trials Register (2008-004968-40). FINDINGS: Between March 27, 2009, and Nov 28, 2011, 276 patients were enrolled and randomised, of whom nine did not receive study medication. 267 patients were included in the primary analysis (placebo, n=133; sorafenib, n=134). With a median follow-up of 36 months (IQR 35.5-38.1), median event-free survival was 9 months (95% CI 4-15) in the placebo group versus 21 months (9-32) in the sorafenib group, corresponding to a 3-year event-free survival of 22% (95% CI 13-32) in the placebo group versus 40% (29-51) in the sorafenib group (hazard ratio [HR] 0.64, 95% CI; 0.45-0.91; p=0.013). The most common grade 3-4 adverse events in both groups were fever (71 [53%] in the placebo group vs 73 [54%] in the sorafenib group), infections (55 [41%] vs 46 [34%]), pneumonia (21 [16%] vs 20 [14%]), and pain (13 [10%] vs 15 [11%]). Grade 3 or worse adverse events that were significantly more common in the sorafenib group than the placebo group were fever (relative risk [RR] 1.54, 95% CI 1.04 2.28), diarrhoea (RR 7.89, 2.94-25.2), bleeding (RR 3.75, 1.5-10.0), cardiac events (RR 3.46, 1.15-11.8), hand-foot-skin reaction (only in sorafenib group), and rash (RR 4.06, 1.25-15.7). INTERPRETATION: In patients with acute myeloid leukaemia aged 60 years or younger, the addition of sorafenib to standard chemotherapy has antileukaemic efficacy but also increased toxicity. Our findings suggest that kinase inhibitors could be a useful addition to curative treatment for acute myeloid leukaemia. Overall survival after long-term follow-up and strategies to reduce toxicity are needed to determine the future role of sorafenib in treatment of this disease. FUNDING: Bayer HealthCare. PMID- 26549592 TI - A new way to target p53-defective colorectal cancer. PMID- 26549593 TI - Overexpression of miR-210 is Associated with Poor Prognosis of Acute Myeloid Leukemia. AB - BACKGROUND: MicroRNAs play important roles in regulation of the initiation and progression of AML. MiR-210 is closely related with cancer development; however, whether miR-210 expression level correlates with clinical correlation in AML is unknown. Thus, the aim of this study was to investigate the potential relationship between miR-210 expression and AML prognosis. MATERIAL AND METHODS: Real-time quantitative PCR was carried out to examine the expression level of miR 210 in bone marrow and serum obtained from AML patients and healthy controls. Then the correlation between miR-210 expression and a variety of important clinical parameters (such as overall survival, relapse-free survival, and prognostic value) were further studied. RESULTS: The expression level of miR-210 was significantly higher in the bone marrow and serum of AML patients than that of healthy controls (p<0.001). Moreover, miR-210 expression was associated with various AML clinicopathological parameters, including FAB classification and cytogenetics. The serum miR-210 expression level was reduced significantly when the patients achieved complete remission (p=0.02). The high miR-210 expression group had both poorer relapse-free survival (p=0.015) and worse overall survival (p=0.008). In the multivariate analysis model, miR-210 was identified as an independent prognostic marker. CONCLUSIONS: MiR-210 up-regulation was associated with poor prognosis in AML and it might be useful as a marker for predicting the clinical outcome of AML patients. PMID- 26549594 TI - Long-Term Degradation of Self-Reinforced Poly-Levo (96%)/Dextro (4%)-Lactide/beta Tricalcium Phosphate Biocomposite Interference Screws. AB - PURPOSE: To evaluate the long-term in vivo degradation of biocomposite interference screws made with self-reinforced poly-levo (96%)/dextro (4%) lactide/beta-tricalcium phosphate [SR-PL(96)/D(4)LA/beta-TCP]. METHODS: A study of the in vivo biologic behavior of an SR-PL(96)/D(4)LA/beta-TCP biocomposite interference screw was initiated in 2011 using an anterior cruciate ligament (ACL) reconstruction model. Eight patients undergoing a bone-patellar tendon-bone ACL reconstruction fixed at both the femur and tibia with an SR PL(96)/D(4)LA/beta-TCP screw at least 36 months earlier were evaluated by physical, radiographic, and computed tomography (CT) evaluations. Lysholm, Tegner, Cincinnati, and International Knee Documentation Committee scores were obtained. After incomplete degradation was observed in these 8 patients, a subsequent series of 17 patients were evaluated at a minimum of 48 months after surgery. By use of CT scans, Hounsfield unit (HU) data were obtained at the femoral and tibial screw and other bone sites. An ossification quality score (range, 1 to 4) was used to determine osteoconductivity at the screw sites. RESULTS: Eleven male and 6 female patients evaluated by CT scan and radiographs at a mean of 50 months (range, 48 to 61 months) after surgery showed bone plug healing to the tunnel wall and the SR-PL(96)/D(4)LA/beta-TCP screws were replaced with material that was calcified and non-trabecular. Osteoconductivity was present in 24 of 34 tunnels (70.58%) and nearly complete or complete (type 3 or 4 ossification) in 11 of 34 (32.35%). Mean screw site densities (femoral, 242 HU; tibial, 240 HU) were consistent with cancellous bone density. One positive pivot shift test was found. Lysholm, Cincinnati, Tegner, and International Knee Documentation Committee activity scores improved from 44.5, 40.7, 2.3, and 1.4, respectively, preoperatively to 92, 92.4, 5.7, and 3.3, respectively, at follow up (P < .0001). The average postoperative Single Assessment Numeric Evaluation score was 92. The mean KT arthrometer (MEDmetric, San Diego, CA) difference was 1.25 mm. CONCLUSIONS: The SR-PL(96)/D(4)LA/beta-TCP interference screw was replaced with calcified, non-trabecular material 4 years after implantation in a bone-patellar tendon-bone ACL reconstruction model. Osteoconductivity was confirmed in 24 of 34 screw sites (71%), with nearly complete or complete filling in 11 of 34 (33%). The SR-PL(96)/D(4)LA/beta-TCP biocomposite interference screw is osteoconductive. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26549595 TI - Psychoactive Properties of Opioids and the Experience of Pain. PMID- 26549597 TI - Correction notice. PMID- 26549596 TI - Interpreting at the End of Life: A Systematic Review of the Impact of Interpreters on the Delivery of Palliative Care Services to Cancer Patients With Limited English Proficiency. AB - CONTEXT: Language barriers can influence the health quality and outcomes of limited English proficiency (LEP) patients at end of life, including symptom assessment and utilization of hospice services. OBJECTIVES: To determine how professional medical interpreters influence the delivery of palliative care services to LEP patients. METHODS: We conducted a systematic review of the literature in all available languages of six databases from 1960 to 2014. Studies evaluated use of language services for LEP patients who received palliative care services. Data were abstracted from 10 articles and collected on study design, size, comparison groups, outcomes, and interpreter characteristics. RESULTS: Six qualitative and four quantitative studies assessed the use of interpreters in palliative care. All studies found that the quality of care provided to LEP patients receiving palliative services is influenced by the type of interpreter used. When professional interpreters were not used, LEP patients and families had inadequate understanding about diagnosis and prognosis during goals of care conversations, and patients had worse symptom management at the end of life, including pain and anxiety. Half of the studies concluded that professional interpreters were not used adequately, and several studies suggested that premeetings between clinicians and interpreters were important to discuss topics and terminology to be used during goals of care discussions. CONCLUSION: LEP patients had worse quality of end-of-life care and goals of care discussions when professional interpreters were not used. More intervention studies are needed to improve the quality of care provided to LEP patients and families receiving palliative services. PMID- 26549598 TI - Self-assembly of tissue spheroids on polymeric membranes. AB - In this study, multicellular tissue spheroids were fabricated on polymeric membranes in order to accelerate the fusion process and tissue formation. To this purpose, tissue spheroids composed of three different cell types, myoblasts, fibroblasts and neural cells, were formed and cultured on agarose and membranes of polycaprolactone (PCL) and chitosan (CHT). Membranes prepared by a phase inversion technique display different physicochemical, mechanical and transport properties, which can affect the fusion process. The membranes accelerated the fusion process of a pair of spheroids with respect to the inert substrate. In this process, a critical role is played by the membrane properties, especially by their mechanical characteristics and oxygen and carbon dioxide mass transfer. The rate of fusion was quantified and found to be similar for fibroblast, myoblast and neural tissue spheroids on membranes, which completed the fusion within 3 days. These spheroids underwent faster fusion and maturation on PCL membrane than on agarose, the rate of fusion being proportional to the value of oxygen and carbon dioxide permeances and elastic characteristics. Consequently, tissue spheroids on the membranes expressed high biological activity in terms of oxygen uptake, making them more suitable as building blocks in the fabrication of tissues and organs. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26549599 TI - Anxiety is associated with increased risk of dementia in older Swedish twins. AB - INTRODUCTION: We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association. METHODS: Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. RESULTS: Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01-1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02 1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95-1.20), indicating genetic mediation. DISCUSSION: Anxiety symptoms were associated with increased risk of dementia. Genetic factors common to dementia and anxiety partially mediated this association. PMID- 26549600 TI - Exercise prescription for non-specific chronic low back pain (NSCLBP): a qualitative study of patients' experiences of involvement in decision making. AB - BACKGROUND: The culture of current clinical practice calls for collaboration between therapists and patients, sharing power and responsibility. This paper reports on the findings of a qualitative study of exercise prescription for patients with NSCLBP, taking into account issues such as decision making and how this accords with patient preferences and experiences. OBJECTIVE: To understand the treatment decision making experiences, information and decision support needs of patients with NSCLBP who have been offered exercise as part of their management plan. DESIGN: A qualitative study using a philosophical hermeneutic approach. METHODS: Semi-structured interviews with eight patients (including use of brief patient vignettes) was undertaken to explore their personal experiences of receiving exercise as part of the management of their NSCLBP, and their involvement in decisions regarding their care. FINDINGS: The findings provide a detailed insight into patients' perceptions and experiences of receiving exercise based management strategies. Four themes were formed from the texts: (1) patients' expectations and patients' needs are not synonymous, (2) information is necessary but often not sufficient, (3) not all decisions need to be shared, and (4) wanting to be treated as an individual. CONCLUSIONS: Shared decision making did not appear to happen in physiotherapy clinical practice, but equally may not be what every patient wants. The overall feeling of the patients was that the therapist was dominant in structuring the interactions, leaving the patients feeling disempowered to question and contribute to the decision making. PMID- 26549601 TI - Exercise adherence: integrating theory, evidence and behaviour change techniques. PMID- 26549605 TI - Accelerated CO2 transport on surface of AgO nanoparticles in ionic liquid BMIMBF4. AB - The AgO nanoparticles were utilized for a CO2 separation membrane. The AgO nanoparticles were successfully generated in ionic liquid 1-butyl-3-methyl imidazolium tetrafluoroborate (BMIMBF4) by favorable interaction between the surface of particles and the counteranion of BMIMBF4. The generated AgO nanoparticles were confirmed by TEM, and the average size was 20 nm. Coordinative interactions of dissociated AgO particles with BMIM(+)BF4(-) were investigated by FT-Raman spectroscopy. When the ionic liquid BMIMBF4 containing AgO nanoparticles was utilized as a CO2 separation membrane, the separation performance was largely enhanced. PMID- 26549607 TI - Electrochemically Preadsorbed Collagen Promotes Adult Human Mesenchymal Stem Cell Adhesion. AB - The present article reports on the effect of electric potential on the adsorption of collagen type I (the most abundant component of the organic phase of bone) onto optically transparent carbon electrodes (OTCE) and its mediation on subsequent adhesion of adult, human, mesenchymal stem cells (hMSCs). For this purpose, adsorption of collagen type I was investigated as a function of the protein concentration (0.01, 0.1, and 0.25 mg/mL) and applied potential (open circuit potential [OCP; control], +400, +800, and +1500 mV). The resulting substrate surfaces were characterized using spectroscopic ellipsometry, atomic force microscopy, and cyclic voltammetry. Adsorption of collagen type I onto OTCE was affected by the potential applied to the sorbent surface and the concentration of protein. The higher the applied potential and protein concentration, the higher the adsorbed amount (Gammacollagen). It was also observed that the application of potential values higher than +800 mV resulted in the oxidation of the adsorbed protein. Subsequent adhesion of hMSCs on the OTCEs (precoated with the collagen type I films) under standard cell culture conditions for 2 h was affected by the extent of collagen preadsorbed onto the OTCE substrates. Specifically, enhanced hMSCs adhesion was observed when the Gammacollagen was the highest. When the collagen type I was oxidized (under applied potential equal to +1500 mV), however, hMSCs adhesion was decreased. These results provide the first correlation between the effects of electric potential on protein adsorption and subsequent modulation of anchorage-dependent cell adhesion. PMID- 26549606 TI - Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies. AB - Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task-related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia-related alterations in task-related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task-related increases or decreases in dystonia patients compared to healthy controls. The meta-analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task-related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task-related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between-group differences in task-related activity were retrieved in a sub analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547-557, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26549609 TI - A rare cause of abdominal pain: Catheter in the middle hepatic vein. AB - Hemodialysis catheters are vital for chronic renal failure patients. Permanent tunneled dialysis catheters may be inserted through the jugular, subclavian, and femoral veins. In this paper, we aimed to present the computed tomography findings of a chronic renal failure patient who had referred our clinic with abdominal pain and dyspnea symptoms. This patient had a formerly inserted hemodialysis catheter for chronic renal failure and her catheter was found to be extending towards the middle hepatic vein with the tip leaning onto the parenchyma. Hemodialysis catheters can provide instant vascular access and can also be used for the consecutive procedures. Permanent hemodialysis catheters are ideal for long-term use when placing an arteriovenous fistula is contraindicated or is no longer possible under conditions like advanced heart failure, peripheral artery disease or short life expectancy. The internal jugular, subclavian, the femoral veins, and the inferior vena cava can be used for catheter insertion. The tip of the catheters inserted in the neck or the thorax must extend to the vena cava superior. Catheter malposition may both lead to fatal outcomes and ineffective dialysis. It is important to obtain chest X-rays after the procedure, particularly to detect catheter malposition. PMID- 26549608 TI - Macrophage accumulation in gut mucosa differentiates AIDS from chronic SIV infection in rhesus macaques. AB - The relationship between recruitment of mononuclear phagocytes to lymphoid and gut tissues and disease in HIV and SIV infection remains unclear. To address this question, we conducted cross-sectional analyses of dendritic cell (DC) subsets and CD163(+) macrophages in lymph nodes (LNs) and ileum of rhesus macaques with acute and chronic SIV infection and AIDS. In LNs significant differences were only evident when comparing uninfected and AIDS groups, with loss of myeloid DCs and CD103(+) DCs from peripheral and mesenteric LNs, respectively, and accumulation of plasmacytoid DCs and macrophages in mesenteric LNs. In contrast, there were fourfold more macrophages in ileum lamina propria in macaques with AIDS compared with chronic infection, and this increased to 40-fold in Peyer's patches. Gut macrophages exceeded plasmacytoid DCs and CD103(+) DCs by ten- to 17 fold in monkeys with AIDS but were at similar low frequencies as DCs in chronic infection. Gut macrophages in macaques with AIDS expressed IFN-alpha and TNF alpha consistent with cell activation. CD163(+) macrophages also accumulated in gut mucosa in acute infection but lacked expression of IFN-alpha and TNF-alpha. These data reveal a relationship between inflammatory macrophage accumulation in gut mucosa and disease and suggest a role for macrophages in AIDS pathogenesis. PMID- 26549610 TI - Analysis of four pentacyclic triterpenoid acids in several bioactive botanicals with gas and liquid chromatography and mass spectrometry detection. AB - Several pentacyclic triterpenoid acids including betulinic, oleanolic, and ursolic acids were reported to have health beneficial properties such as antiviral and anti-inflammatory properties, as well as the capability to inhibit "in vitro" the development of various cancer cell types. For this reason betulinic, oleanolic, and ursolic acids are used as neutraceuticals. For the analysis of the pentacyclic triterpenoid acids in complex plant materials, an improved scheme was developed, involving a qualitative screening using silylation and gas chromatography with mass spectrometry analysis, followed by quantitation using a novel liquid chromatography with tandem mass spectrometry procedure. The use of the two methods provides more reliable information regarding the plant materials with unknown composition. Besides betulinic, oleanolic, and ursolic acids that were analyzed, by this procedure a fourth pentacyclic triterpenoid acid was identified and quantitated that was not previously reported to be present in plants. This acid has been identified as 3beta-3-hydroxy-lupa 18,20(29)-dien-28-oic acid. The newly identified acid has a structure as a derivative of lupane, although lupane with a double bond in the 18-position was not previously reported as present in plants. The new liquid chromatography with tandem mass spectrometry procedure developed for this study offers a very low limit of quantitation, excellent precision, and robustness. Rosemary was found to contain the largest levels of pentacyclic triterpenoid acids among all the analyzed botanicals. PMID- 26549611 TI - Improved strategy for recombinant production and purification of antimicrobial peptide tachyplesin I and its analogs with high cell selectivity. AB - Here, we report an efficient procedure for recombinant production and purification of tachyplesin I (THI) with a final yield of 17 mg/L of the culture medium. The peptide was expressed in Escherichia coli as a part of the thioredoxin fusion protein. With the use of soluble expression followed by immobilized metal-ion affinity chromatography, the recombinant protein cleavage and reversed-phase high-performance liquid chromatography, a yield of THI did not exceed 6.5 mg/L of the culture medium. Further optimization studies were carried out to improve the protein expression level and simplify purification procedure of the target peptide. To achieve better yield of the peptide, we used high-cell density bacterial expression. The formed inclusion bodies were highly enriched with the fusion protein, which allowed us to perform direct chemical cleavage of the inclusion bodies solubilized in 6 M guanidine-HCl with subsequent selective precipitation of proteins with trifluoroacetic acid. This enabled us to avoid an extra step of purification by immobilized metal-ion affinity chromatography. The developed procedure has made it possible to obtain biologically active THI and was used for screening a number of its mutant analogs. As a result, several selective and nonhemolytic analogs were developed. Significant reduction in hemolytic activity without losing antimicrobial activity was achieved by substitution of tyrosine or isoleucine residue in the beta-turn region of the molecule with hydrophilic serine. The present study affords further insight into molecular mechanism of antimicrobial action of tachyplesin and gains a better understanding of structure-activity relationships in its analogs. This is aimed at searching for novel antibiotics on the basis of antimicrobial peptides with reduced cytotoxicity. PMID- 26549612 TI - Sperm traits in farmed and wild Atlantic salmon Salmo salar. AB - Differences in sperm metabolism and morphology between wild and non-local farmed Atlantic salmon Salmo salar were assessed by measuring metabolic enzyme activities and length of sperm flagella. No differences were observed between wild and farmed S. salar sperm with regards to cell counts or any of the biochemical variables assessed. Flagella of sperm cells were significantly longer in wild than farmed S. salar; however, this did not result in higher energy levels or different fertilization rates. PMID- 26549613 TI - What more can be done to popularize phonosurgical ideas in everyday handling of vocal folds? AB - This paper is focused on vocal fold surgery with phonosurgical intent. The aim of this review is to broaden phonosurgical knowledge, spread the ideas of the European Laryngological Society (ELS) on phonosurgery and translate the layered structure and physiology of the vocal fold described in Hirano's classic body cover model into the graphic illustration of the "fluttering sleeve" created by Dikkers. In numerous countries, where phonosurgery is a relatively novel field of knowledge or still in its infancy, simple patterns and plain associations will serve the best in popularizing sophisticated vocal fold anatomy and preservation surgery and converting it into everyday routine. PMID- 26549615 TI - Electrically Tunable Epsilon-Near-Zero (ENZ) Metafilm Absorbers. AB - Enhancing and spectrally controlling light absorption is of great practical and fundamental importance. In optoelectronic devices consisting of layered semiconductors and metals, absorption has traditionally been manipulated with the help of Fabry-Perot resonances. Even further control over the spectral light absorption properties of thin films has been achieved by patterning them into dense arrays of subwavelength resonant structures to form metafilms. As the next logical step, we demonstrate electrical control over light absorption in metafilms constructed from dense arrays of actively tunable plasmonic cavities. This control is achieved by embedding indium tin oxide (ITO) into these cavities. ITO affords significant tuning of its optical properties by means of electrically induced carrier depletion and accumulation. We demonstrate that particularly large changes in the reflectance from such metafilms (up to 15% P) can be achieved by operating the ITO in the epsilon-near-zero (ENZ) frequency regime where its electrical permittivity changes sign from negative to positive values. PMID- 26549614 TI - The role of biology in planetary evolution: cyanobacterial primary production in low-oxygen Proterozoic oceans. AB - Understanding the role of biology in planetary evolution remains an outstanding challenge to geobiologists. Progress towards unravelling this puzzle for Earth is hindered by the scarcity of well-preserved rocks from the Archean (4.0 to 2.5 Gyr ago) and Proterozoic (2.5 to 0.5 Gyr ago) Eons. In addition, the microscopic life that dominated Earth's biota for most of its history left a poor fossil record, consisting primarily of lithified microbial mats, rare microbial body fossils and membrane-derived hydrocarbon molecules that are still challenging to interpret. However, it is clear from the sulfur isotope record and other geochemical proxies that the production of oxygen or oxidizing power radically changed Earth's surface and atmosphere during the Proterozoic Eon, pushing it away from the more reducing conditions prevalent during the Archean. In addition to ancient rocks, our reconstruction of Earth's redox evolution is informed by our knowledge of biogeochemical cycles catalysed by extant biota. The emergence of oxygenic photosynthesis in ancient cyanobacteria represents one of the most impressive microbial innovations in Earth's history, and oxygenic photosynthesis is the largest source of O2 in the atmosphere today. Thus the study of microbial metabolisms and evolution provides an important link between extant biota and the clues from the geologic record. Here, we consider the physiology of cyanobacteria (the only microorganisms capable of oxygenic photosynthesis), their co-occurrence with anoxygenic phototrophs in a variety of environments and their persistence in low-oxygen environments, including in water columns as well as mats, throughout much of Earth's history. We examine insights gained from both the rock record and cyanobacteria presently living in early Earth analogue ecosystems and synthesize current knowledge of these ancient microbial mediators in planetary redox evolution. Our analysis supports the hypothesis that anoxygenic photosynthesis, including the activity of metabolically versatile cyanobacteria, played an important role in delaying the oxygenation of Earth's surface ocean during the Proterozoic Eon. PMID- 26549616 TI - You can go your own way: effectiveness of participant-driven versus experimenter driven processing strategies in memory training and transfer. AB - Cognitive training programs that instruct specific strategies frequently show limited transfer. Open-ended approaches can achieve greater transfer, but may fail to benefit many older adults due to age deficits in self-initiated processing. We examined whether a compromise that encourages effort at encoding without an experimenter-prescribed strategy might yield better results. Older adults completed memory training under conditions that either (1) mandated a specific strategy to increase deep, associative encoding, (2) attempted to suppress such encoding by mandating rote rehearsal, or (3) encouraged time and effort toward encoding but allowed for strategy choice. The experimenter-enforced associative encoding strategy succeeded in creating integrated representations of studied items, but training-task progress was related to pre-existing ability. Independent of condition assignment, self-reported deep encoding was associated with positive training and transfer effects, suggesting that the most beneficial outcomes occur when environmental support guiding effort is provided but participants generate their own strategies. PMID- 26549617 TI - Adenovirus-mediated overexpression of cystic fibrosis transmembrane conductance regulator enhances invasiveness and motility of serous ovarian cancer cells. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate-binding cassette transporter family, members of which are involved in several types of cancer. Previous studies by our group reported that CFTR was highly expressed in serous ovarian cancer (SOC) tissues, and that knockdown of CFTR suppressed the proliferation of ovarian cancer in vitro and in vivo. Thus, the aim of the present study was to construct a recombinant adenoviral vector for the expression of the human CFTR gene in order to study the role of CFTR overexpression in the malignant invasion and migration of SOC cells in vitro. The present study then focused on the mechanisms of the role of CFTR in the migratory and invasive malignant properties of SOC cells. The CFTR gene was inserted into an adenoviral vector by using the AdEasy system in order to obtain the Ad-CFTR overexpression vector, which was used to transfect the A2780 SOC cell line. Reverse-transcription polymerase chain reaction, western blot analysis and immunofluorescence were performed to detect the expression and localization of CFTR. Cell invasion and motility of the transfected cells compared with those of control cells were observed using Transwell and wound healing assays. A ~4,700 bp fragment of the CFTR gene was confirmed to be correctly cloned in the adenoviral vector and amplification of Ad-CFTR was observed in HEK293 cells during package. After 48 h of transfection with Ad-CFTR, ~90% of A2780 cells were red fluorescence protein-positive. Immunofluorescence showed that following transfection, CFTR expression was increased and CFTR was located in the cell membrane and cytoplasm. CFTR overexpression was shown to enhance the invasion and motility of A2780 cells in vitro. Furthermore, the effects of CFTR overexpression on the activation c-Src signaling were observed by western blot analysis. CFTR overexpressing cells showed the lowest activity of phospho-Src (Tyr530), suggesting that CFTR may affect the activation of c-Src signaling. The results of the present study demonstrated that adenovirus-mediated CFTR overexpression enhanced cell invasion and motility of SOC cells in vitro. Furthermore, CFTR may be critical for the activation of c-Src signaling. PMID- 26549618 TI - Observation of Landau levels on nitrogen-doped flat graphite surfaces without external magnetic fields. AB - Under perpendicular external magnetic fields, two-dimensional carriers exhibit Landau levels (LLs). However, it has recently been reported that LLs have been observed on graphene and graphite surfaces without external magnetic fields being applied. These anomalous LLs have been ascribed primarily to a strain of graphene sheets, leading to in-plane hopping modulation of electrons. Here, we report the observation of the LLs of massive Dirac fermions on atomically flat areas of a nitrogen-doped graphite surface in the absence of external magnetic fields. The corresponding magnetic fields were estimated to be as much as approximately 100 T. The generation of the LLs at the area with negligible strain can be explained by inequivalent hopping of pi electrons that takes place at the perimeter of high potential domains surrounded by positively charged substituted graphitic-nitrogen atoms. PMID- 26549619 TI - Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation. AB - Gymnemic acid is a mixture of triterpenoid saponins of oleanane class, isolated from Gymnema sylvestre Wild R.Br (family: Asclepidaceae), an herbal plant used in traditional medicine to treat diabetes. Effect of gymnemic acid (0.1-20 ug/mL) on in vitro mitogen (concanavalin A and lipopolysaccharide)-induced splenic lymphocyte proliferation was studied using rat as model. Significant (p < 0.05) stimulation of lymphoproliferation was observed in cultures treated with 10 and 20 ug/mL concentration of gymnemic acid in the absence or presence of mitogens. The present study suggests that gymnemic acid has immunomodulatory property, stimulating lymphoid components of immune system, and the traditional knowledge of anti-diabetic property of G. sylvestre is scientifically supplemented with its immunomodulatory properties. PMID- 26549620 TI - Reductive cleavage of carbon-chlorine bonds at catalytic and non-catalytic electrodes in 1-butyl-3-methylimidazolium tetrafluoroborate. AB - Dissociative electron transfer (DET) to a series of organic chlorides at glassy carbon (GC), silver and copper electrodes has been studied in 1-butyl-3 methylimidazolium tetrafluoroborate. The overall results of this study show that the ionic liquid behaves like molecular solvents such as acetonitrile and dimethylfomamide. It is found that aromatic chlorides follow a stepwise mechanism, whereas concerted electron transfer/bond cleavage is the preferred reaction mechanism for alkyl and benzyl chlorides. Ag and Cu show catalytic effects only when the DET follows a concerted mechanism, but Ag proves to be a much better electrocatalyst than Cu. A series of substituted benzyl chlorides (Z C6H4CH2Cl, Z = H, 3-OCH3, 3-F, 4-Cl, and 3-CF3) show interesting results providing some insight into the reaction dynamics. The process occurs by a concerted mechanism and, albeit a constant standard potential for the whole series, Ep on GC and Cu, which does not show catalytic activity, is significantly affected by the substituents. In contrast, Ag shows good catalytic activity and, as expected, Ep does not change with the substituent. This difference in behavior may be rationalized by considering ion-dipole interactions between R and Cl(-) as opposed to adsorption of the fragments on the electrode surface. PMID- 26549621 TI - In silico characterization of protein partial molecular volumes and hydration shells. AB - In this paper we present a computational approach, based on NVT molecular dynamics trajectories, that allows the direct evaluation of the protein partial molecular volume. The results obtained for five different globular proteins demonstrate the accuracy of this computational procedure in reproducing protein partial molecular volumes, providing quantitative characterization of the hydration shell in terms of the protein excluded volume, hydration shell ellipsoidal volume and related solvent density. Remarkably, our data indicate for the hydration shell a ~10% solvent density increase with respect to the liquid water bulk density, in excellent agreement with the available experimental data. PMID- 26549622 TI - Fluorogenic nanoreactor assembly with boosted sensing kinetics for timely imaging of cellular hydrogen peroxide. AB - The precise detection of endogenous H2O2 has been considered to be a useful tool for understanding cell physiology. Here, we have developed a nanoreactor co incorporated with a H2O2-responsive fluorogenic molecule and a catalytic additive. The fast sensing kinetics allows us to visualize a subcellular response in real-time. PMID- 26549623 TI - Mesoporous silica formulation strategies for drug dissolution enhancement: a review. AB - INTRODUCTION: Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture. AREAS COVERED: This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered. EXPERT OPINION: Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future. PMID- 26549624 TI - Implications of the Differential Toxicological Effects of III-V Ionic and Particulate Materials for Hazard Assessment of Semiconductor Slurries. AB - Because of tunable band gaps, high carrier mobility, and low-energy consumption rates, III-V materials are attractive for use in semiconductor wafers. However, these wafers require chemical mechanical planarization (CMP) for polishing, which leads to the generation of large quantities of hazardous waste including particulate and ionic III-V debris. Although the toxic effects of micron-sized III-V materials have been studied in vivo, no comprehensive assessment has been undertaken to elucidate the hazardous effects of submicron particulates and released III-V ionic components. Since III-V materials may contribute disproportionately to the hazard of CMP slurries, we obtained GaP, InP, GaAs, and InAs as micron- (0.2-3 MUm) and nanoscale (<100 nm) particles for comparative studies of their cytotoxic potential in macrophage (THP-1) and lung epithelial (BEAS-2B) cell lines. We found that nanosized III-V arsenides, including GaAs and InAs, could induce significantly more cytotoxicity over a 24-72 h observation period. In contrast, GaP and InP particulates of all sizes as well as ionic GaCl3 and InCl3 were substantially less hazardous. The principal mechanism of III-V arsenide nanoparticle toxicity is dissolution and shedding of toxic As(III) and, to a lesser extent, As(V) ions. GaAs dissolves in the cell culture medium as well as in acidifying intracellular compartments, while InAs dissolves (more slowly) inside cells. Chelation of released As by 2,3-dimercapto-1-propanesulfonic acid interfered in GaAs toxicity. Collectively, these results demonstrate that III-V arsenides, GaAs and InAs nanoparticles, contribute in a major way to the toxicity of III-V materials that could appear in slurries. This finding is of importance for considering how to deal with the hazard potential of CMP slurries. PMID- 26549625 TI - Selective Extraction and In Situ Reduction of Precious Metal Salts from Model Waste To Generate Hybrid Gels with Embedded Electrocatalytic Nanoparticles. AB - A hydrogel based on 1,3:2,4-dibenzylidenesorbitol (DBS), modified with acyl hydrazides which extracts gold/silver salts from model waste is reported, with preferential uptake of precious heavy metals over other common metals. Reduction of gold/silver salts occurs spontaneously in the gel to yield metal nanoparticles located on the gel nanofibers. High nanoparticle loadings can be achieved, endowing the gel with electrochemical activity. These hybrid gels exhibit higher conductances than gels doped with carbon nanotubes, and can be used to modify electrode surfaces, enhancing electrocatalysis. We reason this simple, industrially and environmentally relevant approach to conducting materials is of considerable significance. PMID- 26549626 TI - A new face of sleep: The impact of post-learning sleep on recognition memory for face-name associations. AB - Sleep has been demonstrated to improve consolidation of many types of new memories. However, few prior studies have examined how sleep impacts learning of face-name associations. The recognition of a new face along with the associated name is an important human cognitive skill. Here we investigated whether post presentation sleep impacts recognition memory of new face-name associations in healthy adults. Fourteen participants were tested twice. Each time, they were presented 20 photos of faces with a corresponding name. Twelve hours later, they were shown each face twice, once with the correct and once with an incorrect name, and asked if each face-name combination was correct and to rate their confidence. In one condition the 12-h interval between presentation and recall included an 8-h nighttime sleep opportunity ("Sleep"), while in the other condition they remained awake ("Wake"). There were more correct and highly confident correct responses when the interval between presentation and recall included a sleep opportunity, although improvement between the "Wake" and "Sleep" conditions was not related to duration of sleep or any sleep stage. These data suggest that a nighttime sleep opportunity improves the ability to correctly recognize face-name associations. Further studies investigating the mechanism of this improvement are important, as this finding has implications for individuals with sleep disturbances and/or memory impairments. PMID- 26549628 TI - Oscillatory Changes of the Heterogeneous Reactive Layer Detected with the Motional Resistance during the Galvanostatic Deposition of Copper in Sulfuric Solution. AB - Metallic copper was galvanostatically deposited on quartz|gold resonant electrodes by applying a constant current in a 0.5 M CuSO4/0.1 M H2SO4 aqueous solution. Galvanostatic copper deposition is one of the best methodologies to calibrate the electrochemical quartz crystal microbalances (EQCM), a gravimetric sensor to evaluate changes in mass during the electrochemical reactions through the Sauerbrey equation. The simultaneous measurement of mass, current density, and motional resistance by an EQCM with motional resistance monitoring allows us to characterize the processes occurring on the electrode surface and at the interfacial regions with unprecedented detail. During the galvanostatic copper deposition, Cu(H2O)4(OH)2 is accumulated close to the copper surface, generating a passive layer. This passive layer can act as Cu(2+) reservoir for the Cu(2+) -> Cu process since the copper deposition is not affected. The analysis of motional resistance evolution in different experimental conditions reveals that the passive layer is formed by the reaction of oxidizing agents generated at the counter electrode with the metallic copper surface. The simplistic Cu(2+) -> Cu process is completed with a more detailed mechanism, which includes the passive layer formation/dissolution and the transport of species from the counter electrode surface (Pt) to the working electrode surface. The results further support the calibration procedure of EQCM by the galvanostatic deposition of copper in sulfuric solutions. However, we suggest applying high current densities, separating the counter electrode and quartz|gold resonant electrode about 0.5 cm, and keeping oxygen in solution for the EQCM calibration. Moreover, the better interval time to calculate the Sauerbrey's constant from charge and resonant frequency data is between 150 and 300 s. PMID- 26549627 TI - Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness. AB - Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness. PMID- 26549629 TI - Early auditory processing evoked potentials (N100) show a continuum of blunting from clinical high risk to psychosis in a pediatric sample. AB - BACKGROUND: The N100 is a negative deflection in the surface EEG approximately 100 ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms. This phenomenon has received little attention in pediatric populations. METHOD: This cross-sectional study compared the N100 response measured via the average EEG response at the left medial frontal position FC1 to 150 sinusoidal tones in participants ages 5 to 17 years with a CHR syndrome (n=29), a psychotic disorder (n=22), or healthy controls (n=17). RESULTS: Linear regression analyses that considered potential covariates (age, gender, handedness, family mental health history, medication usage) revealed decreasing N100 amplitude with increasing severity of psychotic symptomatology from healthy to CHR to psychotic level. CONCLUSIONS: Longitudinal assessment of the N100 in CHR children who do and do not develop psychosis will inform whether it predicts transition to psychosis and if its response to treatment predicts symptom change. PMID- 26549630 TI - Increased interleukin-2 serum levels were associated with psychopathological symptoms and cognitive deficits in treatment-resistant schizophrenia. AB - Accumulating evidence showed that interleukin-2 (IL-2) may be involved in the pathophysiology of schizophrenia. Increased IL-2 levels have been found in the serum of schizophrenia patients with mixed results. In the present study, we assessed serum IL-2 levels in a large group of 160 schizophrenia patients compared to 60 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum IL-2 levels were measured by sandwich ELISA. The results showed that IL-2 levels were significantly higher in chronic patients with schizophrenia than in healthy control subjects (p<0.001). Correlation analysis revealed a significantly negative association between IL-2 levels and the PANSS cognitive and positive subscales (both p<0.01). Stepwise multiple regression analyses confirmed IL-2 as the influencing factor for the cognitive and positive subscales of the PANSS. Our findings suggested that increased IL-2 may be involved in the cognitive impairments and psychopathology of chronic schizophrenia. PMID- 26549631 TI - A case of pseudo-Stauffer's syndrome related to asenapine use. AB - The authors present a case of suspected pseudo-Stauffer's syndrome in a male with treatment refractory schizoaffective disorder following asenapine use. We discuss our management of this case, and believe knowing about this potential adverse effect and it's management could be useful for clinicians. PMID- 26549632 TI - Effect of organic matter on nitrogenase metal cofactors homeostasis in Azotobacter vinelandii under diazotrophic conditions. AB - Biological nitrogen fixation can be catalysed by three isozymes of nitrogenase: molybdenum (Mo)-nitrogenase, vanadium (V)-nitrogenase and iron-only (Fe) nitrogenase. The activity of these isozymes strongly depends on their metal cofactors, molybdenum, vanadium and iron, and their bioavailability in ecosystems. Here, we show how metal bioavailability can be affected by the presence of tannic acid (organic matter), and the subsequent consequences on diazotrophic growth of the soil bacterium Azotobacter vinelandii. In the presence of tannic acids, A. vinelandii produces a higher amount of metallophores, which coincides with an active, regulated and concomitant acquisition of molybdenum and vanadium under cellular conditions that are usually considered not molybdenum limiting. The associated nitrogenase genes exhibit decreased nifD expression and increased vnfD expression. Thus, in limiting bioavailable metal conditions, A. vinelandii takes advantage of its nitrogenase diversity to ensure optimal diazotrophic growth. PMID- 26549633 TI - The size-dependent morphology of Pd nanoclusters formed by gas condensation. AB - Size-selected Pd nanoclusters in the size range from 887 to 10,000 atoms were synthesized in a magnetron sputtering, inert gas condensation cluster beam source equipped with a time of flight mass filter. Their morphologies were investigated using scanning transmission electron microscopy (STEM) and shown to be strongly size-dependent. The larger clusters exhibited elongated structures, which we attribute to the aggregation, through multiple collisions, of smaller clusters during the gas phase condensation process. This was confirmed from the atomically resolved STEM images of the Pd nanoclusters, which showed smaller primary clusters with their own crystalline structures. PMID- 26549634 TI - Validity of the Special Needs Education Assessment Tool (SNEAT), a Newly Developed Scale for Children with Disabilities. AB - The improvement of the quality of life (QOL) of children with disabilities has been considered important. Therefore, the Special Needs Education Assessment Tool (SNEAT) was developed based on the concept of QOL to objectively evaluate the educational outcome of children with disabilities. SNEAT consists of 11 items in three domains: physical functioning, mental health, and social functioning. This study aimed to verify the reliability and construct validity of SNEAT using 93 children collected from the classes on independent activities of daily living for children with disabilities in Okinawa Prefecture between October and November 2014. Survey data were collected in a longitudinal prospective cohort study. The reliability of SNEAT was verified via the internal consistency method and the test-pretest method; both the coefficient of Cronbach's alpha and the intra-class correlation coefficient were over 0.7. The validity of SNEAT was also verified via one-way repeated-measures ANOVA and the latent growth curve model. The scores of all the items and domains and the total scores obtained from one-way repeated measures ANOVA were the same as the predicted scores. SNEAT is valid based on its goodness-of-fit values obtained using the latent growth curve model, where the values of comparative fit index (0.983) and root mean square error of approximation (0.062) were within the goodness-of-fit range. These results indicate that SNEAT has high reliability and construct validity and may contribute to improve QOL of children with disabilities in the classes on independent activities of daily living for children with disabilities. PMID- 26549635 TI - Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions. AB - Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD. PMID- 26549637 TI - Atopic dermatitis: Age and race do matter! PMID- 26549638 TI - PF-04691502, a dual PI3K/mTOR inhibitor has potent pre-clinical activity by inducing apoptosis and G1 cell cycle arrest in aggressive B-cell non-Hodgkin lymphomas. AB - The PI3K/Akt/mTOR pathway is activated in a variety of human tumors including B cell non-Hodgkin lymphoma (B-NHL). Targeting this pathway has been validated in solid and hematological tumors. In the present study, we demonstrated that PF 04691502, a novel PI3K/mTOR inhibitor has potent activity in a panel of aggressive B-NHL cell lines including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). MTS analysis showed that PF-04691502 effectively inhibited cell proliferation with IC50 values ranging from 0.12 to 0.55 uM. Cells treated with PF-04691502 exhibited decreased phosphorylation of Akt and S6 ribosomal protein confirming the mechanism of action of a PI3K/mTOR inhibitor. Also, treatment of B-NHL cell lines with PF-04691502 induced apoptosis in a dose- and time-dependent manner. Moreover, PF-04691502 significantly induced G1 cell cycle arrest associated with a decrease in cyclin D1 which contributed to suppression of cell proliferation. Finally, rituximab enhanced apoptosis induced by PF-04691502. Taken together, our findings provide for the first time that PF 04691502 inhibits the constitutively activated PI3K/mTOR pathway in aggressive B cell NHL cell lines associated with inhibition of cell cycle progression, cell proliferation and promotion of apoptosis. These findings suggest that PF-04691502 is a novel therapeutic strategy in aggressive B-cell NHL and warrants early phase clinical trial evaluation with and without rituximab. PMID- 26549639 TI - Aging mechanism in model Pickering emulsion. AB - We study the stability of a model Pickering emulsion system using fluorinated oil and functionalized silica nanoparticles. A special counter-flow microfluidic set up was used to prepare monodisperse oil droplets in water. The wettability of the monodisperse silica nanoparticles (NPs) could be tuned by surface grafting and the surface coverage of the droplets was controlled using the microfluidic setup. For surface coverage as low as 23%, we observed a regime of Pickering emulsion stability where the surface coverage of emulsion droplets of constant size increases with time, coexisting with an excess of oil phase. Our results demonstrate that the previously observed limited coalescence regime where surface coverage tends to control the average size of the final droplets must be put in a broader perspective. PMID- 26549641 TI - In vivo real time non invasive monitoring of brain penetration of chemicals with near-infrared spectroscopy: Concomitant PK/PD analysis. AB - BACKGROUND: Near-infrared spectroscopy (NIRS) is a non-invasive technique that monitors changes in oxygenation of haemoglobin. The absorption spectra of near infrared light differ for the oxygenation-deoxygenation states of haemoglobin (oxygenate (HbO2) and deoxygenate (Hb), respectively) so that these two states can be directly monitored. COMPARISON WITH EXISTING METHOD(S): Different methodologies report different basal values of HbO2 and Hb absolute concentrations in brain. Here, we attempt to calculate basal HbO2 levels in rat CNS via evaluation of the influence of exogenous oxygen or exogenous carbon dioxide on the NIRS parameters measured in vivo. NEW METHOD: Furthermore the possibility that changes of haemoglobin oxygenation in rat brain as measured by NIRS might be a useful index of brain penetration of chemical entities has been investigated. Different compounds from different chemical classes were selected on the basis of parallel ex vivo and in vivo pharmacokinetic (PK/PD) studies of brain penetration and overall pharmacokinetic profile. RESULTS: It appeared that NIRS might contribute to assess brain penetration of chemical entities, i.e. significant changes in NIRS signals could be related to brain exposure, conversely the lack of significant changes in relevant NIRS parameters could be indicative of low brain exposure. CONCLUSIONS: This work is proposing a further innovation on NIRS preclinical applications i.e. a "chemical" NIRS [chNIRS] approach for determining penetration of drugs in animal brain. Therefore, chNIRS could became a non invasive methodology for studies on neurobiological processes and psychiatric diseases in preclinical but also a translational strategy from preclinical to clinical investigations. PMID- 26549642 TI - Ligand Exchange Governs the Crystal Structures in Binary Nanocrystal Superlattices. AB - The surface chemistry in colloidal nanocrystals on the final crystalline structure of binary superlattices produced by self-assembly of two sets of nanocrystals is hereby demonstrated. By mixing nanocrystals having two different sizes and the same coating agent, oleylamine (OAM), the binary nanocrystal superlattices that are produced, such as NaCl, AlB2, NaZn13, and MgZn2, are well in agreement with the crystalline structures predicted by the hard-sphere model, their formation being purely driven by entropic forces. By opposition, when large and small nanocrystals are coated with two different ligands [OAM and dodecanethiol (DDT), respectively] while keeping all other experimental conditions unchanged, the final binary structures markedly change and various structures with lower packing densities, such as Cu3Au, CaB6, and quasicrystals, are observed. This effect of the nanocrystals' coating agents could also be extended to other binary systems, such as Ag-Au and CoFe2O4-Ag supracrystalline binary lattices. In order to understand this effect, a mechanism based on ligand exchange process is proposed. Ligand exchange mechanism is believed to affect the thermodynamics in the formation of binary systems composed of two sets of nanocrystals with different sizes and bearing two different coating agents. Hence, the formation of binary superlattices with lower packing densities may be favored kinetically because the required energetic penalty is smaller than that of a denser structure. PMID- 26549640 TI - NADH oxidase-dependent CD39 expression by CD8(+) T cells modulates interferon gamma responses via generation of adenosine. AB - Interferon gamma (IFNgamma)-producing CD8(+) T cells (Tc1) play important roles in immunological disease. We now report that CD3/CD28-mediated stimulation of CD8(+) T cells to generate Tc1 cells, not only increases IFNgamma production but also boosts the generation of reactive oxygen species (ROS) and augments expression of CD39. Inhibition of NADPH oxidases or knockdown of gp91phox in CD8(+) T cells abrogates ROS generation, which in turn modulates JNK and NFkappaB signalling with decreases in both IFNgamma levels and CD39 expression. CD39(+)CD8(+) T cells substantially inhibit IFNgamma production by CD39(-)CD8(+) T cells via the paracrine generation of adenosine, which is operational via adenosine type 2A receptors. Increases in numbers of CD39(+)CD8(+) T cells and associated enhancements in ROS signal transduction are noted in cells from patients with Crohn's disease. Our findings provide insights into Tc1-mediated IFNgamma responses and ROS generation and link these pathways to CD39/adenosine mediated effects in immunological disease. PMID- 26549643 TI - Genetic and phenotypic correlations among feed efficiency, production and selected conformation traits in dairy cows. AB - The difficulties and costs of measuring individual feed intake in dairy cattle are the primary factors limiting the genetic study of feed intake and utilisation, and hence the potential of their subsequent industry-wide applications. However, indirect selection based on heritable, easily measurable, and genetically correlated traits, such as conformation traits, may be an alternative approach to improve feed efficiency. The aim of this study was to estimate genetic and phenotypic correlations among feed intake, production, and feed efficiency traits (particularly residual feed intake; RFI) with routinely recorded conformation traits. A total of 496 repeated records from 260 Holstein dairy cows in different lactations (260, 159 and 77 from first, second and third lactation, respectively) were considered in this study. Individual daily feed intake and monthly BW and body condition scores of these animals were recorded from 5 to 305 days in milk within each lactation from June 2007 to July 2013. Milk yield and composition data of all animals within each lactation were retrieved, and the first lactation conformation traits for primiparous animals were extracted from databases. Individual RFI over 301 days was estimated using linear regression of total 301 days actual energy intake on a total of 301 days estimated traits of metabolic BW, milk production energy requirement, and empty BW change. Pair-wise bivariate animal models were used to estimate genetic and phenotypic parameters among the studied traits. Estimated heritabilities of total intake and production traits ranged from 0.27+/-0.07 for lactation actual energy intake to 0.45+/-0.08 for average body condition score over 301 days of the lactation period. RFI showed a moderate heritability estimate (0.20+/-0.03) and non-significant phenotypic and genetic correlations with lactation 3.5 % fat corrected milk and average BW over lactation. Among the conformation traits, dairy strength, stature, rear attachment width, chest width and pin width had significant (P<0.05) moderate to strong genetic correlations with RFI. Combinations of these conformation traits could be used as RFI indicators in the dairy genetic improvement programmes to increase the accuracy of the genetic evaluation of feed intake and utilisation included in the index. PMID- 26549644 TI - Excess salt exacerbates blood-brain barrier disruption via a p38/MAPK/SGK1 dependent pathway in permanent cerebral ischemia. AB - High salt diet (HSD) is one of the most important risk factors that contribute to many vascular diseases including ischemic stroke. One proposed mechanism underlying the disruption of blood-brain barrier (BBB) mediated by HSD is indirectly through enhancing blood pressure. The direct role of HSD on BBB integrity is unclear. Our purpose is to determine whether and how HSD might be involved in BBB breakdown during ischemia. To test that, we induced model of cerebral ischemia by permanent middle cerebral artery ligation (pMCAL) in either normal diet or HSD fed mice. We observed that HSD significantly enhanced ischemic brain damage which was associated with enhanced BBB disruption, increased leukocytes infiltration and loss of tight junction (TJ) proteins expression without apparently altering blood pressure. Our in vitro experiment also revealed that sodium chloride (NaCl) treatment down-regulated TJ protein expression by endothelial cells and substantially increased BBB permeability during starvation. Inhibition of p38/MAPK/SGK1 pathway eliminated the effect of NaCl on BBB permeability in vitro. In addition, we noticed a positive correlation between urinary sodium levels and ischemic lesion size in stroke patients. Together, our study demonstrates a hypertension-independent role of HSD during ischemia and provides rationale for post cerebral ischemic attack management. PMID- 26549646 TI - New transcription factors involved with postnatal ventral prostate gland development in male Wistar rats during the first week. AB - AIMS: The high incidence in men of prostatic diseases, including benign and malignant tumors, makes the understanding of prostate development and biology very important. Understanding the organogenesis of the prostate gland has been a substantial challenge as "prostatic code" is not well defined at the present time. The novelty of this work lies in unveiling new transcription factors (TFs) during neonatal ventral prostate (VP) gland development in male Wistar rats. MAIN METHODS: The techniques of qRT-PCR and immunohistochemistry have been employed to perform this work while the VP gland was obtained from neonatal rats at day zero (the day of birth) day 3 and 6. KEY FINDINGS: 16 TFs were studied and we found an increased expression of Eya2, Lhrh and Znf142, invariable levels of Znf703 and Dbp, and decreased expression of 11 others at postnatal development day 3 and 6 as compared to day zero. ZNF703 was found by immunohistochemistry in epithelial cells at days 0, 3 and 6. qRT-PCR for Eya2 and Dmrt2 showed the highest and lowest fold change for them respectively, and immunohistochemistry showed that the former is being expressed at the three selected time points while the latter appears to be diminishing with very few cells expressing it until day 6. SIGNIFICANCE: Results from this work is reporting the role of these TFs for the first time and will significantly contribute to the current understanding of the development and branching morphogenesis of the neonatal VP gland during the first week of postnatal development. PMID- 26549645 TI - Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology. AB - Neuropeptide Y (NPY) is a sympathetic neurotransmitter with pleiotropic actions, many of which are highly relevant to tumor biology. Consequently, the peptide has been implicated as a factor regulating the growth of a variety of tumors. Among them, two pediatric malignancies with high endogenous NPY synthesis and release - neuroblastoma and Ewing sarcoma - became excellent models to investigate the role of NPY in tumor growth and progression. The stimulatory effect on tumor cell proliferation, survival, and migration, as well as angiogenesis in these tumors, is mediated by two NPY receptors, Y2R and Y5R, which are expressed in either a constitutive or inducible manner. Of particular importance are interactions of the NPY system with the tumor microenvironment, as hypoxic conditions commonly occurring in solid tumors strongly activate the NPY/Y2R/Y5R axis. This activation is triggered by hypoxia-induced up-regulation of Y2R/Y5R expression and stimulation of dipeptidyl peptidase IV (DPPIV), which converts NPY to a selective Y2R/Y5R agonist, NPY(3-36). While previous studies focused mainly on the effects of NPY on tumor growth and vascularization, they also provided insight into the potential role of the peptide in tumor progression into a metastatic and chemoresistant phenotype. This review summarizes our current knowledge of the role of NPY in neuroblastoma and Ewing sarcoma and its interactions with the tumor microenvironment in the context of findings in other malignancies, as well as discusses future directions and potential clinical implications of these discoveries. PMID- 26549647 TI - Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review. AB - Organochlorine pesticides (OCPs) are persistent and bioaccumulative environmental contaminants with potential neurotoxic effects. The growing body of evidence has demonstrated that prenatal exposure to organochlorines (OCs) is associated with impairment of neuropsychological development. The hypothesis is consistent with recent studies emphasizing the correlation of environmental as well as genetic factors to the pathophysiology of neurodevelopmental and neurobehavioral defects. It has been suggested that maternal exposure to OCPs results in impaired motor and cognitive development in newborns and infants. Moreover, in utero exposure to these compounds contributes to the etiology of autism. Although impaired neurodevelopment occurs through prenatal exposure to OCs, breastfeeding causes postnatal toxicity in the infants. Parkinson's disease (PD) is another neurological disorder, which has been associated with exposure to OCs, leading to alpha-synuclein accumulation and depletion of dopaminergic neurons. The study aimed to review the potential association between pre- and post-natal exposure to OCs and impaired neurodevelopmental processes during pregnancy and neuropsychological diseases such as PD, behavioral alterations, seizures and autism. PMID- 26549648 TI - Imiquimod inhibits the growth of SGC-7901 cells in vitro through induction of autophagy and apoptosis. AB - Imiquimod, the most prominent Toll-like receptor 7 agonist, has direct anti-tumor activity and can induce autophagy and apoptosis in various types of human cancer. The aim of the present study was to examine the anti-tumor effects of imiquimod and their underlying mechanisms in SGC-7901 cells. Imiquimod exerted an inhibitory effect on cell proliferation in a dose- and time-dependent manner as indicated by an MTT assay. Imiquimod induced autophagy as well as apoptosis, while simultaneous treatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased the toxicity of imiquimod. Furthermore, blocking of autophagy by 3-MA exerted an inhibitory effect on imiquimod-induced apoptosis, which indicated that autophagy can function as a mechanism which, upon activation, directly leads to apoptosis and cell death of SGC-7901 cells. The results of the present study suggested that imiquimod has potent direct activity against gastric cancer cells by inducing autophagy and apoptosis. PMID- 26549650 TI - Development and Characterization of a Microemulsion System Containing Amphotericin B with Potential Ocular Applications. AB - BACKGROUND: Amphotericin B eye drops are widely used in the treatment of ocular infections. However, amphotericin's toxicity leads to low patient compliance and aggravation of symptoms. This work describes the development of a microemulsion system containing amphotericin B, aiming for its use in ocular applications. METHODS: The microemulsion was developed by the titration technique. The physicochemical characteristics were determined with both loaded and unloaded amphotericin B-microemulsion. The nanostructures were analyzed by polarized light microscopy. The microdilution method was used to establish the minimum inhibitory concentration against fungal strains, and, therefore, evaluate the microemulsion activity. Additionally, in order to evaluate the microemulsion toxicity an in vitro toxicity assay against red blood cells was performed. RESULTS: The performed studies showed that the presence of amphotericin B loaded into the system did not induce serious changes in the physicochemical properties of the microemulsion when compared to the unloaded system. The spectrophotometric studies depicted amphotericin B-self-associated species, which allow predicting its behavior in vitro. The high pressure liquid chromatography results revealed high drug content entrapment in the microemulsion droplet. Finally, the amphotericin B-microemulsion in vitro susceptibility test showed high activity against Candida strains and a low toxicity profile against red blood cells when compared to Fungizone(r). CONCLUSION: The physicochemical characterization of the microemulsion demonstrated that its characteristics are compatible with the topical ocular route, making it eligible for consideration as a new and interesting amphotericin B-deliverydosage form to be used as eye drop formulation. PMID- 26549649 TI - Selenium in the Therapy of Neurological Diseases. Where is it Going? AB - Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson's disease, Alzheimer's disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies. Undoubtedly, the remarkable progress that has been made in understanding the biological function of Se in the brain has opened up new potential possibilities for the treatment of neurological diseases by using Se as a potential drug. However, further research in the search for optimal Se donors is necessary in order to achieve an effective and safe therapeutic income. PMID- 26549652 TI - Mutational analysis of mitochondrial DNA in Brugada syndrome. AB - BACKGROUND: Brugada syndrome (BrS) is a primary electrical disease associated with an increased risk of sudden cardiac death due to ventricular fibrillation. This pathology has nuclear heterogeneous genetic origins, and at present, molecular diagnostic tests on nuclear DNA cover only 30% of BrS patients. The aim of this study was to assess the possible involvement of mitochondrial (mt) DNA variants in BrS since their etiological role in several cardiomyopathies has already been described. METHODS AND RESULTS: The whole mt genome of BrS patients was sequenced and analyzed. A specific mtDNA mutation responsible for BrS can be excluded, but BrS patient d-loop was found to be more polymorphic than that of control cases (P=0.003). Moreover, there appears to be an association between patients with the highest number of variants (n>20) and four mt Single Nucleotide Polymorphism (SNPs) (T4216C, A11251G, C15452A, T16126C) and the most severe BrS phenotype (P=0.002). CONCLUSIONS: The high substitution rate found in BrS patient mtDNA is unlikely to be the primary cause of the disease, but it could represent an important cofactor in the manifestation of the BrS phenotype. Evidence suggesting that a specific mtDNA allelic combination and a high number of mtDNA SNPs may be associated with more severe cases of BrS represents the starting point for further cohort studies aiming to test whether this mt genetic condition could be a genetic modulator of the BrS clinical phenotype. PMID- 26549653 TI - An Acute Encephalopathy Accelerated by a Large Amount of Milk Consumption. PMID- 26549654 TI - From Novice to Seasoned Practitioner: a Qualitative Investigation of Genetic Counselor Professional Development. AB - Research on genetic counselor professional development would characterize typical developmental processes, inform training and supervision, and promote life-long development opportunities. To date, however no studies have comprehensively examined this phenomenon. The aims of this study were to investigate the nature of professional development for genetic counselors (processes, influences, and outcomes) and whether professional development varies across experience levels. Thirty-four genetic counselors participated in semi-structured telephone interviews exploring their perspectives on their professional development. Participants were sampled from three levels of post-degree genetic counseling experience: novice (0-5 years), experienced (6-14 years), and seasoned (>15 years). Using modified Consensual Qualitative Research and grounded theory methods, themes, domains, and categories were extracted from the data. The themes reflect genetic counselors' evolving perceptions of their professional development and its relationship to: (a) being a clinician, (b) their professional identity, and (c) the field itself. Across experience levels, prevalent influences on professional development were interpersonal (e.g., experiences with patients, genetic counseling colleagues) and involved professional and personal life events. Common developmental experiences included greater confidence and less anxiety over time, being less information-driven and more emotion-focused with patients, delivering "bad news" to patients remains challenging, and individuals' professional development experiences parallel genetic counseling's development as a field. With a few noteworthy exceptions, professional development was similar across experience levels. A preliminary model of genetic counselor professional development is proposed suggesting development occurs in a non-linear fashion throughout the professional lifespan. Each component of the model mutually influences the others, and there are positive and negative avenues of development. PMID- 26549655 TI - GlycA, a marker of acute phase glycoproteins, and the risk of incident type 2 diabetes mellitus: PREVEND study. AB - BACKGROUND: GlycA is a recently developed glycoprotein biomarker of systemic inflammation that may be predictive of incident type 2 diabetes mellitus (T2DM). METHODS: Analytical performance of the GlycA test, measured on the Vantera(r) Clinical Analyzer, was evaluated. To test its prospective association with T2DM, GlycA was measured in 4524 individuals from the PREVEND study and a survival analysis was performed with a mean follow-up period of 7.3y. RESULTS: Imprecision for the GlycA test ranged from 1.3-2.3% and linearity was established between 150 and 1588MUmol/l. During the follow-up period, 220 new T2DM cases were ascertained. In analyses adjusted for relevant covariates, GlycA was associated with incident T2DM; hazard ratio (HR) for the highest vs. lowest quartile 1.77 [95% Confidence Interval (CI): 1.10-2.86, P=0.01], whereas the association of high sensitivity C-reactive protein (hsCRP) with T2DM was not significant. GlycA remained associated with incident T2DM after additional adjustment for hsCRP; HR 1.71 [1.00-2.92, P=0.04]. A multivariable adjusted analysis of dichotomized subgroups showed that the hazard for incident T2DM was highest in the subgroup with high GlycA and low hsCRP (P=0.03). CONCLUSIONS: The performance characteristics of the GlycA test reveal that it is suitable for clinical applications, including assessment of the risk of future T2DM. PMID- 26549656 TI - Novel nonsense mutation (p.Ile411Metfs*12) in the SLC19A2 gene causing Thiamine Responsive Megaloblastic Anemia in an Indian patient. AB - Thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive disorder, is caused by mutations in SLC19A2 gene encodes a high affinity thiamine transporter (THTR-1). The occurrence of TRMA is diagnosed by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Here, we report a female TRMA patient of Indian descent born to 4th degree consanguineous parents presented with retinitis pigmentosa and vision impairment, who had a novel homozygous mutation (c.1232delT/ter422; p.Ile411Metfs*12) in 5th exon of SLC19A2 gene that causes premature termination of hTHTR-1. PROSITE analysis predicted to abrogate GPCRs family-1 signature motif in the variant by this mutation c.1232delT/ter422, suggesting uncharacteristic rhodopsin function leading to cause RP clinically. Thiamine transport activity by the clinical variant was severely inhibited than wild-type THTR-1. Confocal imaging had shown that the variant p.I411Mfs*12 is targeted to the cell membrane and showed no discrepancy in membrane expression than wild-type. Our findings are the first report, to the best of our knowledge, on this novel nonsense mutation of hTHTR-1 causing TRMA in an Indian patient through functionally impaired thiamine transporter activity. PMID- 26549651 TI - Can We Selectively Reduce Appetite for Energy-Dense Foods? An Overview of Pharmacological Strategies for Modification of Food Preference Behavior. AB - Excessive intake of food, especially palatable and energy-dense carbohydrates and fats, is largely responsible for the growing incidence of obesity worldwide. Although there are a number of candidate antiobesity drugs, only a few of them have been proven able to inhibit appetite for palatable foods without the concurrent reduction in regular food consumption. In this review, we discuss the interrelationships between homeostatic and hedonic food intake control mechanisms in promoting overeating with palatable foods and assess the potential usefulness of systemically administered pharmaceuticals that impinge on the endogenous cannabinoid, opioid, aminergic, cholinergic, and peptidergic systems in the modification of food preference behavior. Also, certain dietary supplements with the potency to reduce specifically palatable food intake are presented. Based on human and animal studies, we indicate the most promising therapies and agents that influence the effectiveness of appetite-modifying drugs. It should be stressed, however, that most of the data included in our review come from preclinical studies; therefore, further investigations aimed at confirming the effectiveness and safety of the aforementioned medications in the treatment of obese humans are necessary. PMID- 26549657 TI - Atypical plasma lipid profiles in leukemia. AB - Numerous studies have reported alterations in the plasma lipid profiles of leukemia patients. However, there are several inconsistencies in these reports. The present review highlights and compiles findings from different research groups regarding association of plasma lipoprotein levels with the risk of developing leukemia. We have also discussed the clinical significance of plasma lipid profiles in management of leukemia. Furthermore, the potential role of plasma lipids in promoting leukemogenesis is also highlighted. PMID- 26549658 TI - TBMS1 exerts its cytotoxicity in NCI-H460 lung cancer cells through nucleolar stress-induced p53/MDM2-dependent mechanism, a quantitative proteomics study. AB - Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1 induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-kappaB signaling pathways. PMID- 26549659 TI - The use of turning tasks in clinical gait analysis for children with cerebral palsy. AB - BACKGROUND: Turning while walking is a crucial component of locomotion that is performed using an outside (step) or inside (spin) limb strategy. The aims of this paper were to determine how children with cerebral palsy perform turning maneuvers and if specific kinematic and kinetic adaptations occur compared to their typically developing peers. METHODS: Motion capture data from twenty-two children with cerebral palsy and fifty-four typically developing children were collected during straight and 90 degrees turning gait trials. Experimental data were used to compute spatio-temporal parameters, margin of stability, ground reaction force impulse, as well as joint kinematics and kinetics. FINDINGS: Both child groups preferred turning using the spin strategy. The group of children with cerebral palsy exhibited the following adaptations during turning gait compared to the typically developing group: stride length was decreased across all phases of the turn with largest effect size for the depart phase (2.02), stride width was reduced during the turn phase, but with a smaller effect size (0.71), and the average margin of stability during the approach phase of turning was reduced (effect size of 0.98). Few overall group differences were found for joint kinematic and kinetic measures; however, in many cases, the intra-subject differences between straight walking and turning gait were larger for the majority of children with cerebral palsy than for the typically developing children. INTERPRETATION: In children with cerebral palsy, turning gait may be a better discriminant of pathology than straight walking and could be used to improve the management of gait abnormalities. PMID- 26549660 TI - Ewing's sarcoma of the cervix, a diagnostic dilemma: a case report and review of the literature. AB - INTRODUCTION: Ewing's sarcoma belongs to a spectrum of neoplastic diseases known as Ewing's family of tumors. This family of tumors is usually seen in osseous sites. Ewing's sarcoma of the cervix is extremely rare, with only 18 cases reported in the English literature. The immunohistochemical profile of Ewing's sarcoma overlaps with other malignancies like small cell carcinoma. The rarity and complex pathologic picture of Ewing's sarcoma of the cervix creates the potential for misdiagnosis. Hence, we believe this case needs to be reported to add to the available literature. CASE PRESENTATION: A 49-year-old white Caucasian woman presented with vaginal bleeding. A pelvic examination revealed a cystic lesion arising from her cervix. Examination of a biopsy specimen revealed a poorly differentiated neoplasm, with sheets of small hyperchromatic cells, staining weakly for neuroendocrine markers. She was diagnosed with small cell carcinoma and started on concurrent chemotherapy and radiation. However, additional positive immunostaining for CD99 was strongly suggestive of Ewing's sarcoma. Fluorescence in situ hybridization revealed ESWR1 gene rearrangement, confirming Ewing's sarcoma. Our patient underwent surgery, which confirmed stage IIB Ewing's sarcoma. She received adjuvant chemotherapy but died from progressive metastatic disease after four cycles. CONCLUSION: With early diagnosis and appropriate treatment, Ewing's sarcoma of the cervix can be a potentially curable disease. However, owing to overlapping clinical and histopathological features, the diagnosis poses a challenge to oncologists and pathologists. This article guides pathologists to consider Ewing's sarcoma in the differential diagnosis of small cell carcinoma with weak staining for neuroendocrine markers. This literature review will benefit oncologists encountering this rare entity. PMID- 26549661 TI - Electroanalytical devices with pins and thread. AB - This work describes the adaptive use of conventional stainless steel pins-used in unmodified form or coated with carbon paste-as working, counter, and quasi reference electrodes in electrochemical devices fabricated using cotton thread or embossed omniphobic R(F) paper to contain the electrolyte and sample. For some applications, these pin electrodes may be easier to modify and use than printed electrodes, and their position and orientation can be changed as needed. Electroanalytical devices capable of multiplex analysis (thread-based arrays or 96-well plates) were easily fabricated using pins as electrodes in either thread or omniphobic R(F) paper. PMID- 26549663 TI - Transfer efficiency of Staphylococcus aureus between nitrile exam gloves and nonporous fomites. AB - This report describes fomite transmission of Staphylococcus aureus amongst various surfaces. A contact transfer protocol was completed to evaluate the movement of S aureus between a person wearing nitrile gloves and either: handshaking with another person with gloved hands, touching a plastic cellular telephone back, or touching a stainless steel rod. The data in this preliminary study imply that the highest bacterial transfer is with metal surfaces followed by plastic. Interestingly, glove-to-glove transfer occurred but transfered less bacteria than a plastic or metal surface. The observations from this study point to the need to clearly define hygiene behaviors to reduce the potential of hand- and surface-mediated transmission. PMID- 26549662 TI - Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation. AB - Irreversible electroporation (IRE) with microsecond-pulsed electric fields (MUsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after MUsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that MUsPEF ablation affects liver tissue and is less effective in vessels, which enable MUsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation. PMID- 26549664 TI - PrP genotype frequencies and risk evaluation for scrapie in dairy sheep breeds from southern Italy. AB - Concerns regarding scrapie in sheep breeding have increased in the last few decades. The present study was carried out in dairy sheep breeds from southern Italy. In order to find breeding animals resistant to scrapie, the PrP genes of 1,205 animals from entire flocks of dairy native Apulian Leccese and Altamurana breeds, and Sicilian Comisana breed, were analysed for polymorphisms at codons 136, 154, and 171 related to scrapie resistance/susceptibility. The Altamurana breed was considered as two populations (Alt-Cav and Alt-Cra-Zoe), based on presumed cross-breeding. A total of five alleles and ten different genotypes were found. The ARQ allele was predominant for all breeds followed by ARR, the most resistant allele to scrapie, which was highly prevalent in Comisana (50%) and in native Alt-Cav (42.4%). The VRQ allele, associated with the highest susceptibility to scrapie, was detected at not negligeable levels in allocthonous Comisana (3.5%), at a low frequency (0.2%) in native Leccese and Alt-Cra-Zoe, while it was absent in Alt-Cav. The frequencies of PrP genotypes with a very low susceptibility risk to scrapie (R1) was higher in Comisana and Alt-Cav. The most susceptible genotype, ARQ/VRQ, was found only in Comisana. Within the Altamurana breed, there were notable differences between Alt-Cav and Alt-Cra-Zoe sheep. The Alt-Cav was characterised by the absence of VRQ and AHQ alleles and by the higher frequency of the ARR/ARR genotype (18.7%). Breeding programs, mainly in endangered breeds such as Altamurana, should be conducted gradually, combining resistance to scrapie, maintenance of genetic variability, and production. PMID- 26549665 TI - Creating a model to detect dairy cattle farms with poor welfare using a national database. AB - The objective of this study was to determine whether dairy farms with poor cow welfare could be identified using a national database for bovine identification and registration that monitors cattle deaths and movements. The welfare of dairy cattle was assessed using the Welfare Quality((r)) protocol (WQ) on 24 Portuguese dairy farms and on 1930 animals. Five farms were classified as having poor welfare and the other 19 were classified as having good welfare. Fourteen million records from the national cattle database were analysed to identify potential welfare indicators for dairy farms. Fifteen potential national welfare indicators were calculated based on that database, and the link between the results on the WQ evaluation and the national cattle database was made using the identification code of each farm. Within the potential national welfare indicators, only two were significantly different between farms with good welfare and poor welfare, 'proportion of on-farm deaths' (p<0.01) and 'female/male birth ratio' (p<0.05). To determine whether the database welfare indicators could be used to distinguish farms with good welfare from farms with poor welfare, we created a model using the classifier J48 of Waikato Environment for Knowledge Analysis. The model was a decision tree based on two variables, 'proportion of on-farm deaths' and 'calving to-calving interval', and it was able to correctly identify 70% and 79% of the farms classified as having poor and good welfare, respectively. The national cattle database analysis could be useful in helping official veterinary services in detecting farms that have poor welfare and also in determining which welfare indicators are poor on each particular farm. PMID- 26549666 TI - Local anesthetics exacerbate antibiotic-induced anaphylactic shock. PMID- 26549667 TI - Prediction of intra-hospital mortality after severe trauma: which pre-hospital score is the most accurate? AB - PURPOSE: Computing trauma scores in the field allows immediate severity assessment for appropriate triage. Two pre-hospital scores can be useful in this context: the Triage-Revised Trauma Score (T-RTS) and the Mechanism, Glasgow, Age and arterial Pressure (MGAP) score. The Trauma Revised Injury Severity Score (TRISS), not applicable in the pre-hospital setting, is the reference score to predict in-hospital mortality after severe trauma. The aim of this study was to compare T-RTS, MGAP and TRISS in a cohort of consecutive patients admitted in the Trauma system of the Northern French Alps(TRENAU). MATERIALS AND METHODS: From 2009 to 2011, 3260 patients with suspected severe trauma according to the Vittel criteria were included in the TRENAU registry. All data necessary to compute T RTS, MGAP and TRISS were collected in patients admitted to one level-I, two level II and ten level-III trauma centers. The primary endpoint was death from any cause during hospital stay. Discriminative power of each score to predict mortality was measured using receiver operating curve (ROC) analysis. To test the relevancy of each score for triage, we also tested their sensitivity at usual cut offs. We expected a sensitivity higher than 95% to limit undertriage. RESULTS: The TRISS score showed the highest area under the ROC curve (0.95 [CI 95% 0.94 0.97], p<0.01). Pre-hospital MGAP score had significantly higher AUC compared to T-RTS (0.93 [CI 95% 0.91-0.95] vs 0.86 [CI 95% 0.83-0.89], respectively, p<0.01). MGAP score<23 had a sensitivity of 88% to detect mortality. Sensitivities of T RTS<12 and TRISS<0.91 were 79% and 87%, respectively. DISCUSSION/CONCLUSION: Pre hospital calculation of the MGAP score appeared superior to T-RTS score in predicting intra-hospital mortality in a cohort of trauma patients. Although TRISS had the highest AUC, this score can only be available after hospital admission. These findings suggest that the MGAP score could be of interest in the pre-hospital setting to assess patients' severity. However, its lack of sensitivity indicates that MGAP should not replace the decision scheme to direct the most severe patients to level-I trauma center. PMID- 26549668 TI - Rationale for more consistent choice of surgical approaches for acetabular fractures. AB - OBJECTIVES: All acetabular fractures are difficult to treat surgically, but there are four types involving two columns that are particularly challenging. The choice of surgical approach is crucial. The purpose of the study was to determine and evaluate the factors influencing the choice of surgical approach for two column acetabular fractures. We hypothesised that more accurate preoperative planning, sophisticated technical capabilities, and evolution of surgeon experience will result in more consistent use of non-extensile single surgical approaches. We also evaluated the outcomes of surgical treatment and the correlation with the surgical approach used. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: A total of 156 patients with 157 acetabular fractures involving two columns (Letournel T-types and both-column) treated surgically in a 25-year period (1988-2013) were included in the study. The acetabular fractures in this study were divided into two groups according to the date of surgery: 81 in Group 1 (1998-2002) and 76 in Group 2 (2003-2013). All fractures were classified preoperatively according to the Judet and Letournel classification system and Matta's categorisation of surgical approach. Four surgical approaches were used: single Kocher-Langenbeck (KL), single ilioinguinal (II), combined Kocher-Langenbeck and ilioinguinal (KL+II), and extended iliofemoral (EIF). The efficacy of the surgical approach utilised was assessed using three parameters: anatomical reduction, surgical time and intraoperative complications. RESULTS: There was no statistical difference between Group 1 and Group 2 in the distribution of T-type (p=0.424) and both-column (p=0.425) fractures. In Group 2 more acetabular fractures were treated through single non-extensile approaches compared with Group 1 (90.8% vs. 54.3%, p<0.001). Increase in single approach surgery resulted in shorter mean surgical time (p<0.001) and significant increase in anatomical reduction (p=0.039). The frequency of intraoperative complications was not statistically different (p=0.07) between the two groups, but there was a trend to fewer complications in Group 2. CONCLUSIONS: The surgical approaches chosen for acetabular fractures that involve two columns (Letournel T-types and both-column) should become more consistent. The results of this study indicate that the majority of such acetabular fractures can be treated successfully through single surgical approaches. PMID- 26549669 TI - Implementing the Surgical Apgar Score in patients with trauma hip fracture. AB - BACKGROUND: Trauma hip fractures in elderly patients are associated with high postoperative long-term morbidity and mortality and premature death. The high mortality in these patients can be explained by various factors, including the fracture itself; the preoperative poor condition and comorbidities of these patients; the influence of stressors, such as surgery and type of anaesthesia, on the patient's condition; and the postoperative development of major complications, such as cardiac failure, pulmonary embolism, pneumonia, deep venous thrombosis and acute renal failure. Thus, the Surgical Apgar Score (SAS) could be a valuable tool for objective risk stratification of patients immediately after surgery, and to enable patients with higher risk to receive postoperative ICU care and good management both during and after the hospital stay. METHODS: The SAS was calculated retrospectively from the handwritten anaesthesia records of 43 trauma hip fracture patients treated operatively in the University Hospital Centre Zagreb over a 1-year period. The primary endpoints were the 30-days major postoperative complications and mortality, length of the ICU and hospital stay, and 6-months major complications development. Statistical analysis was applied to compare SAS with the patients' perioperative variables. RESULTS: A SAS<=4 in the trauma hip fracture patients was a significant predictor for the 30-days major postoperative complications with 80% specificity (95% CI: 0.587-0.864, p=0.0111). However, the SAS was not significant in the prediction of 30-days mortality (95% CI: 0.468-0.771, p=0.2238) and 6-months mortality (95% CI: 0.497-0.795, p=0.3997) as primary endpoints in the hip fracture surgery patients. CONCLUSION: The SAS shows how intraoperative events affect postoperative outcomes. Calculating the SAS in the operating theatre provides immediate, reliable, real-time feedback information about patient postoperative risk. The results of this study indicate that all trauma hip fracture patients with SAS<=4 should go to the ICU postoperatively and should be under intensive surveillance both during the hospital stay and after hospital discharge. PMID- 26549670 TI - Knockdown of long non-coding RNA HOTAIR inhibits proliferation and invasiveness and improves radiosensitivity in colorectal cancer. AB - Colorectal cancer (CRC) is still one of the most important neoplasias causing human death. Multidisciplinary therapy has won consensus in the management of CRC, of which, radiotherapy occupies an important position. However, radioresistance is still a major obstacle in local control of CRC. Overexpression of long non-coding RNA HOTAIR has been found to correlate with tumorigenesis and poor prognosis in several types of cancer. In the present study, we analyzed HOTAIR expression levels of 53 CRC patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of HOTAIR by RNA interference was performed to explore its roles in cell proliferation, migration, invasion, apoptosis and radiosensitivity. Results showed that CRC patients had higher HOTAIR expression in tumor tissues compared with adjacent normal tissues. In vitro, downregulation of HOTAIR reduced proliferation, migration and invasiveness while enhanced apoptosis and radio-sensitivity of CRC cells. Taken together, our findings suggest that long non-coding RNA HOTAIR expression is closely associated with tumor invasion and radiosensitivity, indicating the potential role in diagnostics and therapeutics of CRC. PMID- 26549671 TI - Differences between calcium-stimulated and storage-induced erythrocyte-derived microvesicles. AB - Microvesicles (MVs), or microparticles, are a complex, dynamic and functional part of cells. Red blood cell (RBC)-derived MVs are naturally produced in vivo (during normal aging processes or in several diseases) as well as ex vivo during cold storage of RBCs, or in vitro by ATP depletion or treatment with Ca(2+) and calcium ionophore. All these MVs are equivalently classified according to their size and/or surface markers. Nevertheless, their content in proteins can differ and a few differences in terms of lipid raft proteins, notably stomatin and flotillin-2, have been reported. Based on two-dimensional gel electrophoreses, the present study highlights the differences between MVs induced during storage of RBCs (storage-MVs) and MVs stimulated by Ca(2+) entry (Ca-MVs). Upon treatment, Ca-MVs are formed following a clear recruitment of Ca(2+)-binding proteins (sorcin, grancalcin, PDCD6) and particularly annexins (4 and 5). Therefore, it emerges that different molecular pathways are available to produce similar MVs by disturbing the membrane/cytoskeleton interactions. Interestingly, these differences provide non-negligible pieces of information on the parent cells, and the mechanisms and modes of actions involved in the formation of MVs. In addition to biophysical characterization, protein analysis is important to classify these cellular corpuscles and evaluate their potential impacts in diseases or transfusion medicine. PMID- 26549672 TI - Platelet microparticles in cryopreserved platelets: Potential mediators of haemostasis. AB - Platelet concentrates can be cryopreserved in dimethylsulphoxide (DMSO) and stored at -80 degrees C, which increases the shelf-life from 5 days to up to 4 years. Cryopreserved platelets have been shown to contain a high number of microparticles that have in vitro haemostatic activity. Further, when transfused, cryopreserved platelets have been shown to be at least as haemostatically active, as liquid-stored platelets, if not more so. Given that microparticles are traditionally considered to be pro-coagulant, it is likely that their presence in the cryopreserved component contributes to this haemostatic effect. However, as microparticles are known to mediate many physiological and pathological processes, including in thrombosis and cancer development and progression, further work is warranted to fully understand the functional scope of the microparticles in cryopreserved platelets. PMID- 26549673 TI - Do obese patients have worse outcomes after direct lateral interbody fusion compared to non-obese patients? AB - Obese patients undergoing lumbar spinal fusion surgery are a challenge to the operating surgeon. Direct lateral interbody fusion (DLIF) has been performed for degenerative disease of the lumbar spine with good outcomes; nevertheless, how obese patients fare compared to non-obese patients after DLIF remains unknown. The primary aim of this study is to compare rates of postoperative complications and long-term outcomes between obese and non-obese patients undergoing DLIF. Sixty-three patients (obese: 29, non-obese: 34) undergoing index DLIF for degenerative disease of the spine between 2010 and 2012 at our institution were retrospectively enrolled. We analyzed data on demographics, postoperative complications, back and leg pain, and functional disability over 2 years. Patients completed the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) back and leg pain numerical rating scores before surgery, then at 12 and 24 months after surgery. Outcomes and complication rates were compared between the cohorts. The cohorts were similar at baseline. Postoperative complications rates were similar between obese and non-obese patients. There was no statistically significant difference in the incidence of durotomy (p=0.91), anterior thigh numbness (p=0.60), cerebrospinal fluid leak (p=0.91), postoperative infection (p=0.37), or bleeding requiring transfusion (p=0.16). No patient experienced a nerve injury or psoas hematoma. Both cohorts had similar 2 year improvement in VAS for back pain, leg pain, and ODI. Our study demonstrates that obese and non obese patients undergoing DLIF have similar complication profiles; hence, a patient's weight should not be a contraindication to DLIF. PMID- 26549674 TI - Risk factors associated with distal catheter migration following ventriculoperitoneal shunt placement. AB - Ventriculoperitoneal (VP) shunt placement is used to treat hydrocephalus. Shunt migration following VP shunt placement has been reported. The risk factors related to this complication have not been previously evaluated to our knowledge. In this retrospective cohort study, we aimed to determine risk factors leading to distal catheter migration and review the literature on the current methods of management and prevention. Adult patients undergoing VP shunt placement from June 2011 to December 2013 at a single institution were identified using electronic health records. The records were reviewed for demographic and procedural information, and subsequent treatment characteristics. The parameters of patients with distal shunt migration were compared to those undergoing new VP shunt placement for the same time period. We identified 137 patients undergoing 157 new VP shunt procedures with an average age of 57.7 +/- standard deviation of 18.4 years old. There were 16 distal shunt migrations. Body mass index >30 kg/m(2) and number of previous shunt procedures were found to be independent risk factors for distal catheter migration. Obesity and number of previous shunt procedures were factors for distal catheter migration. Providers and patients should be aware of these possible risk factors prior to VP shunt placement. PMID- 26549675 TI - Recurrent glioblastoma: Current patterns of care in an Australian population. AB - This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, p<0.0001). All patients progressed after treatment for first progression with 43 patients (45%) receiving treatment at second progression. To our knowledge this is the first population-based pattern of care survey of treatment for rGBM in an era where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy. PMID- 26549676 TI - A novel technique for identifying the fistulous point in a direct carotid cavernous fistula. AB - The fistulous point in a direct carotid-cavernous fistula (CCF) can often be difficult to identify because of high-flow shunting. A novel technique that is useful for identifying the fistulous point is reported. A 71-year-old woman underwent endovascular therapy for a left direct CCF that presented with sudden diplopia and tinnitus. To identify the fistulous point, vertebral angiography with manual compression of the left carotid artery was attempted, as was slow injection of a contrast agent from a balloon guiding catheter, closing off the left internal carotid artery; however, the shunt flow was very rapid, and identification was not possible. Therefore, three-dimensional digital subtraction angiography of the vertebral artery was performed while also performing manual aspiration from the balloon guiding catheter, closing off the left internal carotid artery. This reduced early visualization of the cavernous sinus and enabled an aneurysm in the cavernous sinus to be clearly visualized. Embolization was performed transarterially and transvenously, and the shunt flow disappeared completely. Vertebral angiography combined with manual aspiration from a balloon guiding catheter closing off the internal carotid artery is useful for identifying the fistulous point in a direct CCF. PMID- 26549677 TI - Unusual presentation of unilateral intra-orbital optic nerve pilocytic astrocytoma of the juvenile type in a geriatric patient. AB - Optic nerve gliomas (ONG) are rare and seldom encountered in clinical practice. The pilocytic (astrocytoma) variant of ONG almost always presents during the first two decades of life. In this report, the authors discuss an unusual presentation of pilocytic astrocytoma of the juvenile type in an elderly Indian male. With this unusual presentation, ONG affecting the visual pathway should be considered as a possible differential of visual diminution in the elderly population. PMID- 26549678 TI - Atypical case of Morvan's syndrome. AB - Morvan's syndrome is a rare neurological condition characterized by the combination of neuromyotonia, autonomic instability and encephalopathy, associated with auto-antibodies against voltage-gated potassium channels. We report a patient with an initial presentation suggestive of typical Guillain Barre syndrome (GBS), who later developed clinical and laboratory features compatible with Morvan's syndrome. Several months after resolution of the neurological symptoms, as well as disappearance of the characteristic anti leucine-rich, glioma inactivated 1 (anti-LGI1) antibodies, the patient presented with episodes of fever of unknown origin, during which the antibodies became positive again, suggesting the possibility of a relapse. In this case, both the GBS-like symptoms at presentation and the isolated episodes of fever of unknown origin during follow-up are atypical, and may suggest the presence of an additional, yet unknown antibody. PMID- 26549679 TI - Endovascular treatment of posterior fossa arteriovenous malformations. AB - Infratentorial arteriovenous malformations (AVM) are rare, representing only 7 15% of cerebral AVM. The concentration of eloquent neurological structures and the high rate of bleeding presentation of AVM in this location complicate the management of such lesions. New therapeutic options, especially in endovascular therapy, have fundamentally modified the treatment strategy and also the outcome of posterior fossa AVM. Between 1999 and 2013, baseline, clinical and angiographic data of cerebral AVM were prospectively collected. We analyzed data from patients treated for a posterior fossa AVM, focusing on risk factors for bleeding, and clinical and angiographic outcomes. Sixty-nine patients (mean age 34 years, male to female ratio 2:1) were consecutively treated for an infratentorial AVM. Fifty-seven presented with hemorrhage, six with focal neurologic deficits, and the remaining six patients were diagnosed incidentally. The Spetzler-Martin grade was < 3 in 39 (56.5%) patients. Associated aneurysms were noted in 43.5% of patients. All patients were treated using endovascular procedures, associated with microsurgical resection in nine patients and with stereotactic radiosurgery in six. Mean follow-up was 28.5 months, with angiographic exclusion of the AVM in 72.5% of patients; 21.7% of patients presented a modified Rankin Score ? 3 at follow-up. Endovascular embolization seems to be a secure approach for posterior fossa AVM although a large number of sessions are necessary to achieve complete obliteration. Multi-disciplinary discussion and management is crucial to obtain the best cure rate without increasing procedural risks. PMID- 26549680 TI - The role and safety of the sitting position in instrumented cervical surgery. AB - Placing patients who are undergoing neurosurgical procedures to the cervical spine in the sitting position offers significant advantages. These must be counterbalanced against the risk of venous and paradoxical air embolism. This study addresses the role and safety of the sitting position for instrumented cervical surgery. Twenty-five consecutive patients who underwent instrumented cervical surgery in the sitting position were recruited via retrospective analysis. Complications arising from the surgical procedure - specifically venous air embolism - were recorded, as well as pre- and post-operative haemoglobin levels. The incidence of venous air embolism was 0% (97.5% one-sided confidence interval: 0-13.7%). However, five other complications occurred (incidence rate of 20% with a 95% confidence interval of 6.8-40.7%). With appropriate precautions, screening and specific indications, the sitting position can be safely used in more complex instrumented cervical surgery. PMID- 26549681 TI - Petrous apex cephalocele presenting with cerebrospinal fluid rhinorrhea in an adult. AB - Petrous apex cephalocele (PAC) is a rare condition with very few case reports in the literature. We report a 26-year-old man with cerebrospinal fluid rhinorrhea that was misdiagnosed elsewhere and operated unsuccessfully via the endonasal route. CT cisternography revealed a 3mm right PAC for which he underwent a right subtemporal extradural approach and successful repair. We present what is to our knowledge the first case report in the literature of an adult presenting with cerebrospinal fluid leak and discuss the diagnostic dilemmas in the diagnosis of PAC, difficulties in management and review the available literature. PMID- 26549682 TI - Measuring In Vivo Mitophagy. AB - Alterations in mitophagy have been increasingly linked to aging and age-related diseases. There are, however, no convenient methods to analyze mitophagy in vivo. Here, we describe a transgenic mouse model in which we expressed a mitochondrial targeted form of the fluorescent reporter Keima (mt-Keima). Keima is a coral derived protein that exhibits both pH-dependent excitation and resistance to lysosomal proteases. Comparison of a wide range of primary cells and tissues generated from the mt-Keima mouse revealed significant variations in basal mitophagy. In addition, we have employed the mt-Keima mice to analyze how mitophagy is altered by conditions including diet, oxygen availability, Huntingtin transgene expression, the absence of macroautophagy (ATG5 or ATG7 expression), an increase in mitochondrial mutational load, the presence of metastatic tumors, and normal aging. The ability to assess mitophagy under a host of varying environmental and genetic perturbations suggests that the mt-Keima mouse should be a valuable resource. PMID- 26549683 TI - Continuous Histone Replacement by Hira Is Essential for Normal Transcriptional Regulation and De Novo DNA Methylation during Mouse Oogenesis. AB - The integrity of chromatin, which provides a dynamic template for all DNA-related processes in eukaryotes, is maintained through replication-dependent and independent assembly pathways. To address the role of histone deposition in the absence of DNA replication, we deleted the H3.3 chaperone Hira in developing mouse oocytes. We show that chromatin of non-replicative developing oocytes is dynamic and that lack of continuous H3.3/H4 deposition alters chromatin structure, resulting in increased DNase I sensitivity, the accumulation of DNA damage, and a severe fertility phenotype. On the molecular level, abnormal chromatin structure leads to a dramatic decrease in the dynamic range of gene expression, the appearance of spurious transcripts, and inefficient de novo DNA methylation. Our study thus unequivocally shows the importance of continuous histone replacement and chromatin homeostasis for transcriptional regulation and normal developmental progression in a non-replicative system in vivo. PMID- 26549685 TI - Efficient kinetic resolution of (+/-)-menthol by a lipase from Thermomyces lanuginosus. AB - A lipase from Thermomyces lanuginosus (Lipozyme TL IM) exhibited high enantioselectivity for kinetic resolution of (+/-)-menthol in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied. The optimum reaction conditions for the transesterification reaction were found with vinyl acetate in the solvent of methyl tert-butyl ether with a vinyl acetate:(+/-)-menthol molar ratio of 5:1 and an enzyme concentration of 200 g/L at 30 degrees C. In these conditions, (-)-menthyl acetate with 99.3% enantiomeric excess was obtained, whereas the conversion was 34.7% with the reaction time of 12 H at the substrate concentration of 0.5 M. In addition, the enzyme allowed the substrate loading to be increased up to 1.5 M without the decrease of the enantioselectivity. These results indicated that Lipozyme TL IM was a promising biocatalyst in the resolution of (+/-)-menthol. PMID- 26549684 TI - Single-Molecule Imaging Reveals a Switch between Spurious and Functional ncRNA Transcription. AB - Eukaryotic transcription is pervasive, and many of the resulting RNAs are non coding. It is unknown whether ubiquitous transcription is functional or simply reflects stochastic transcriptional noise. By single-molecule visualization of the dynamic interplay between coding and non-coding transcription at the GAL locus in living yeast cells, we show that antisense GAL10 ncRNA transcription can switch between functional and spurious under different conditions. During galactose induction, GAL10 sense transcription occurs in short stochastic bursts, which are unaffected by transcription of antisense GAL10 ncRNA, even when both are present simultaneously at the same locus. In contrast, when GAL10 is not induced, ncRNA transcription is critical to prevent transcriptional leakage of GAL1 and GAL10. Suppression of ncRNA transcription by strand-specific CRISPR/dCas9 results in transcriptional leakage of the inducer GAL1, leading to a more sensitive transcription activation threshold, an alteration of metabolic switching, and a fitness defect in competition experiments. PMID- 26549686 TI - [Recurrent fevers in childhood]. AB - Recurrent fevers are defined as multiple stereotypical febrile episodes separated by spontaneous symptom-free intervals and occurring for months and years. Hereditary recurrent fevers are rare prototype Mendelian diseases due to inherited mutations in genes encoding partners of the innate immunity. Recurrent episodes of fever plus acute features of inflammation starting during childhood with family history are the main clues for suspecting HRF. Their common associated complication is AA amyloidosis. The diagnosis is made on clinical grounds but the genetic diagnosis may contribute in most cases of monogenic hereditary recurrent fevers. Recurrent fevers must be distinguished from intermittent fevers, mostly infectious, characterized by variation in associated symptoms from episode-to-episode and without periodicity. PMID- 26549687 TI - [Cluster headache differential diagnosis]. AB - Cluster headache is characterized by disabling stereotyped headache. Early diagnosis allows appropriate treatment, unfortunately diagnostic errors are frequent. The main differential diagnoses are other primary or essential headaches. Migraine, more frequent and whose diagnosis is carried by excess, trigeminal neuralgia or other trigemino-autonomic cephalgia. Vascular or tumoral underlying condition can mimic cluster headache, neck and brain imaging is recommended, ideally MRI. PMID- 26549688 TI - Transcription regulation of nuclear receptor PXR: Role of SUMO-1 modification and NDSM in receptor function. AB - Pregnane & Xenobiotic Receptor (PXR) is one of the 48 members of the nuclear receptor superfamily of ligand-modulated transcription factors. PXR plays an important role in metabolism and elimination of diverse noxious endobiotics and xenobiotics. Like in case of some nuclear receptors its function may also be differentially altered, positively or negatively, by various post-translational modifications. In this context, regulation of PXR function by SUMOylation is the subject of present investigation. Here, we report that human PXR is modified by SUMO-1 resulting in its enhanced transcriptional activity. RT-PCR analysis showed that PXR SUMOylation in presence of rifampicin also enhances the endogenous expression levels of key PXR-regulated genes like CYP3A4, CYP2C9, MDR1 and UGT1A1. In addition, mammalian two-hybrid assay exhibited enhanced interaction between PXR and co-activator SRC-1. EMSA results revealed that SUMOylation has no influence on the DNA binding ability of PXR. In silico analysis suggested that PXR protein contains four putative SUMOylation sites, centered at K108, K129, K160 and K170. In addition to this, we identified the presence of NDSM (Negative charge amino acid Dependent SUMOylation Motif) in PXR. Substitution of all its four putative lysine residues along with NDSM abolished the effect of SUMO-1 mediated transactivation function of PXR. Furthermore, we show that interaction between PXR and E2-conjugation enzyme UBCh9, an important step for implementation of SUMOylation event, was reduced in case of NDSM mutant PXRD115A. Overall, our results suggest that SUMOylation at specific sites on PXR protein are involved in enhancement of transcription function of this receptor. PMID- 26549689 TI - Effects of orexin A on glucose metabolism in human hepatocellular carcinoma in vitro via PI3K/Akt/mTOR-dependent and -independent mechanism. AB - Orexins are hypothalamic neuropeptides that regulate food intake, energy homeostasis, reward system and sleep/wakefulness states. The purpose of this study was to investigate the effects of orexin A on glucose metabolism in human hepatocellular carcinoma cell line, Hep3B, and determine the possible mechanisms. Hep3B cells were incubated with different concentrations of orexin A (10(-9)-10( 7) M) in vitro in the presence or absence of the orexin receptor 1 (OX1R) inhibitor (SB334867), Akt inhibitor (PF-04691502) and mammalian target of rapamycin (mTOR) inhibitor (temsirolimus). Subsequently, OX1R protein expression, glucose transporter 1 (GLUT1) expression, glucose uptake, the mRNA expression of lactate dehydrogenase (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase B (PDHB), lactate generation and mitochondrial pyruvate dehydrogenase (PDH) enzyme activity were measured. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was also determined. OX1R was expressed in hepatoma tissues and Hep3B cells. Stimulation of the Hep3B cells with orexin A resulted in a dose-dependent increase of GLUT1 expression and glucose uptake, which was associated with the activation of PI3K/Akt/mTOR pathway. Further, orexin A increased PDHB expression and PDH enzyme activity, decreased LDHA, PDK1 mRNA levels and lactate generation independent of PI3K/Akt/mTOR pathway. Our results demonstrated that orexin A directed the cellular metabolism towards mitochondrial glucose oxidation rather than glycolysis. These findings provide functional evidence of the metabolic actions of orexin A in hepatocellular carcinoma cells. PMID- 26549690 TI - Needle Fixation Profile: An Exploratory Assessment of Applicability in the Australian Context. AB - BACKGROUND: Needle fixation has the potential to undermine harm-reduction efforts and may affect up to one-quarter of all injecting drug users (IDUs). Being largely ignored in the extant literature, the majority of research on this phenomenon has been carried out exclusively in Cardiff, Wales. OBJECTIVES: The current exploratory study examined the applicability of needle fixation in a population of Australian IDUs to determine whether Australian IDUs were familiar with the behaviors and secondary gains that have been found to be associated with needle fixation and are assessed by the needle fixation profile (NEFPRO). METHODS: A mixed-method design utilizing semi-structured interviews and questionnaire data was employed. RESULTS: Australian IDUs were aware of or had experience with the behaviors and secondary gains that have been found to be associated with needle fixation. A number of other behaviors and secondary gains associated with injecting were discussed by participants during the semi structured interviews. CONCLUSIONS/IMPORTANCE: This study offers preliminary support for the use of NEFPRO as a clinical and research tool within Australia. To ensure that all avenues toward harm reduction are being explored, it would be fruitful to engage in further research concerning the cross-cultural representations of needle fixation specifically as well as the general influence of needle fixation in perpetuating injecting drug use. PMID- 26549691 TI - Conceptual and Operational Definitions of the Defining Characteristics and Related Factors of the Diagnosis Ineffective Health Management in People With Heart Failure. AB - OBJECTIVE: To construct conceptual and operational definitions for the defining characteristics (DCs) and related factors (RFs) of the nursing diagnosis (ND) ineffective health management for people with chronic heart failure. METHOD: Conceptual and operational definitions for the DC and RF were based on studies found in an integrative literature review in the databases Latin American Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, and MEDLINE by using the key words Nursing diagnosis, Heart Failure, and Patient Cooperation in different combinations. RESULTS: Conceptual and operational definitions for all the DCs and RFs were constructed. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The definitions will facilitate in the identification of ND in clinical practice in patients with heart failure, future research on ND validation, and education in undergraduate courses. PMID- 26549692 TI - Pregnancy-Induced ISG-15 and MX-1 Gene Expression is Detected in the Liver of Holstein-Friesian Heifers During Late Peri-Implantation Period. AB - The bovine embryonic signal interferon-tau (IFN-tau) produced by the trophoblast is known to pass through the uterine fluid towards the endometrium and further into the maternal blood, where IFN-tau induces specific expression of interferon stimulated gene expression (ISG), for example in peripheral leucocytes. In sheep, it was shown experimentally by administration of IFN-tau that ISG is also detectable in the liver. The objective was to test whether ISG can be detected in liver biopsy specimens from Holstein-Friesian heifers during early pregnancy. Liver biopsies were taken on day 18 from pregnant and non-pregnant heifers (n = 19), and the interferon-stimulated protein 15 kDa (ISG-15) and myxovirus resistance protein-1 (MX-1) gene expression was detected. The expression of both MX-1 (p: 24.33 +/- 7.40 vs np: 9.00 +/- 4.02) and ISG-15 (p: 43.73 +/- 23.22 vs 7.83 +/- 3.63) was higher in pregnant compared to non-pregnant heifers (p < 0.05). In conclusion, pregnancy induced ISG-15 and MX-1 gene expression in the liver already at day 18 in cattle. PMID- 26549693 TI - Impact of c-erbB-2 protein on 5-year survival rate of gastric cancer patients after surgery: a cohort study and meta-analysis. AB - OBJECTIVE: To explore the association of c-erbB-2 protein expression with clinicopathological characteristics and prognosis of gastric cancer (GC) after surgery. METHODS: A total of 133 patients undergoing surgical resection for GC between March 2006 and January 2009 in the Second Affiliated Hospital of Wenzhou Medical University were included in this study. c-erbB-2 protein expression was determined by immunohistochemistry. Afterwards, a meta-analysis was performed to further confirm the association between c-erbB-2 protein expression and GC by employing stringent inclusion and exclusion criteria. All data analyses were conducted with STATA 12.0 and SPSS 19.0. RESULTS: There was no significant difference in c-erbB-2 expression among patients with various parameters including age, gender and histological types (all p>0.05). Among 133 GC patients, 32 patients presented c-erbB-2-positive expression and 101 presented c-erbB-2 negative expression (24.1% vs. 75.9%). The c-erbB-2-positive expression rate was significantly higher in GC tissues of patients with lymph node metastasis than those without. Similarly, a significant increase in c-erbB-2 expression was observed in well/moderately differentiated GC tissues compared with poorly differentiated GC. Patients with negative c-erbB-2 expression had a higher 5-year survival rate than those with positive c-erbB-2 expression, which was consistent with the results of the meta-analysis (OR = 0.54, 95% CI 0.37-0.80, p = 0.002). CONCLUSIONS: Our study demonstrated that high expression of c-erbB-2 protein was strongly associated with lymph node metastasis, histological differentiation and 5-year survival rate in GC patients after surgery. PMID- 26549694 TI - A hierarchical view on material formation during pulsed-laser synthesis of nanoparticles in liquid. AB - Pulsed-laser assisted nanoparticle synthesis in liquids (PLAL) is a versatile tool for nanoparticle synthesis. However, fundamental aspects of structure formation during PLAL are presently poorly understood. We analyse the spatio temporal kinetics during PLAL by means of fast X-ray radiography (XR) and scanning small-angle X-ray scattering (SAXS), which permits us to probe the process on length scales from nanometers to millimeters with microsecond temporal resolution. We find that the global structural evolution, such as the dynamics of the vapor bubble can be correlated to the locus and evolution of silver nanoparticles. The bubble plays an important role in particle formation, as it confines the primary particles and redeposits them to the substrate. Agglomeration takes place for the confined particles in the second bubble. Additionally, upon the collapse of the second bubble a jet of confined material is ejected perpendicularly to the surface. We hypothesize that these kinetics influence the final particle size distribution and determine the quality of the resulting colloids, such as polydispersity and modality through the interplay between particle cloud compression and particle release into the liquid. PMID- 26549695 TI - Obeticholic acid for the treatment of primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy. PMID- 26549696 TI - A whole new ball game: Stem cell-derived epithelia in the study of host-microbe interactions. AB - Recent advances in developmental and stem cell biology have resulted in techniques that enable the generation and maintenance of complex epithelium in vitro. While these models have been utilized to study host development and disease, a renewed appreciation of host-microbe interactions has sparked interest in employing these new techniques to study microbes at the epithelial interface. Here we review the current advances in host-microbe interactions that have resulted from experiments using these complex epithelia. Furthermore we highlight aspects of these techniques that warrant further development to facilitate the study of host-microbe interactions. PMID- 26549697 TI - Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms. AB - We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19-9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words). PMID- 26549698 TI - Restraint Reduction at a Pediatric Psychiatric Hospital: A Ten-Year Journey. AB - BACKGROUND: Restraints are used as one of the safety interventions for children and adolescents in various community, hospital, and treatment settings. Although considered safety interventions, restraints are known to have many adverse effects on children and staff, including injuries; even reports of death are noted in the literature. OBJECTIVE: In an effort to reduce the use of restraints and to provide trauma-informed care in a 52-bed Pediatric Psychiatric Hospital, a quality improvement project was launched. INTERVENTIONS: Primary prevention principles based on trauma-informed and strength-based care were utilized to provide care for children and adolescents. Hospital leadership played an instrumental role in bringing positive culture change. Staff involvement and training in restraint reduction and prevention tools played a key role in this project. Debriefing and problem solving were effective interventions for the prevention of restraints. Involvement of youth and family in treatment planning built stronger relationships with staff and paved the way for better communication and trust, and improved understanding of strengths and needs of children and adolescents. RESULTS: Over a 10-year period, mechanical restraints decreased by 100%, from 485 in 2005 to "zero" in 2014 and none in the last 3 years. Physical restraints decreased by 88%, from 3,033 in 2005 to 379 in 2014. PMID- 26549699 TI - Oil-in-oil emulsions stabilised solely by solid particles. AB - A brief review of the stabilisation of emulsions of two immiscible oils is given. We then describe the use of fumed silica particles coated with either hydrocarbon or fluorocarbon groups in acting as sole stabilisers of emulsions of various vegetable oils with linear silicone oils (PDMS) of different viscosity. Transitional phase inversion of emulsions, containing equal volumes of the two oils, from silicone-in-vegetable (S/V) to vegetable-in-silicone (V/S) occurs upon increasing the hydrophobicity of the particles. Close to inversion, emulsions are stable to coalescence and gravity-induced separation for at least one year. Increasing the viscosity of the silicone oil enables stable S/V emulsions to be prepared even with relatively hydrophilic particles. Predictions of emulsion type from calculated contact angles of a silica particle at the oil-oil interface are in agreement with experiment provided a small polar contribution to the surface energy of the oils is included. We also show that stable multiple emulsions of V/S/V can be prepared in a two-step procedure using two particle types of different hydrophobicity. At fixed particle concentration, catastrophic phase inversion of emulsions from V/S to S/V can be effected by increasing the volume fraction of vegetable oil. Finally, in the case of sunflower oil + 20 cS PDMS, the study is extended to particles other than silica which differ in chemical type, particle size and particle shape. Consistent with the above findings, we find that only sufficiently hydrophobic particles (clay, zinc oxide, silicone, calcium carbonate) can act as efficient V/S emulsion stabilisers. PMID- 26549700 TI - Rethinking regeneration: empowerment of stem cells by inflammation. PMID- 26549701 TI - MiRNAs as biomarkers of high-risk pancreatic cysts: a possible holy grail for the early detection of pancreatic cancer. PMID- 26549702 TI - Identification and Characterization of Baicalin as a Phosphodiesterase 4 Inhibitor. AB - Asthma is a chronic inflammatory disease of lung airways, and pharmacological inhibitors of cyclic adenosine monophosphate-specific phosphodiesterase 4 (PDE4) have been considered as therapeutics for the treatment of asthma. However, development of PDE4 inhibitors in clinical trials has been hampered because of the severe side effects of non-selective PDE4 inhibitors. Here, screening of a plant extract library in conjunction with dereplication technology led to identification of baicalin as a new type of PDE4-selective inhibitor. We demonstrated that while rolipram inhibited the enzyme activity of a range of PDE4 subtypes in in vitro enzyme assays, baicalin selectively inhibited the enzyme activity of PDE4A and 4B. In addition, baicalin suppressed lipopolysaccharide induced TNF-alpha expression in macrophage where PDE4B plays a key role in lipopolysaccharide-induced signaling. Furthermore, baicalin treatment in an animal model of allergic asthma reduced inflammatory cell infiltration and TNF alpha levels in bronchoalveolar lavage fluids, indicating that the antiinflammatory effects of baicalin in vivo are attributable, in part, to its ability to inhibit PDE4. PMID- 26549703 TI - NET formation can occur independently of RIPK3 and MLKL signaling. AB - The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor-interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3-deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently of both RIPK3 and MLKL signaling. PMID- 26549705 TI - Rosemary Lowe-McConnell 1921-2014 (Freshwater Biological Association and British Museum of Natural History). PMID- 26549704 TI - Utility of a single serum testosterone measurement to determine response to topical testosterone replacement in hypogonadal men. AB - OBJECTIVE: To evaluate the utility of single serum testosterone measurement in patients receiving transdermal testosterone therapy. RESEARCH DESIGN AND METHODS: Data were from an open-label, 120 day, multi-center titration trial in androgen deficient men receiving an initial daily dose of 60 mg testosterone (testosterone topical solution 2%) applied to axillae (30 mg/axilla). Average concentration (Cavg) of serum testosterone (TT) was determined on days 15, 60, and 120; doses were adjusted to maintain normal Cavg (300-1050 ng/dL [10.4-36.4 nmol/L]). Accuracy of single serum TT measurements (2, 4, 8, 12, 16, and 20 hours post dose) was assessed in patients with Cavg TT within and below (<300 ng/dL [<10.4 nmol/L]) the normal range. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov - NCT00702650. MAIN OUTCOME MEASURE: Serum testosterone levels. RESULTS: In patients with normal Cavg (n = 85), 79% to 92% had serum testosterone levels within normal range 2, 4, 8, 12, 16, and 20 hours post-dose; significant effects of time post-dose for single testosterone measurement accuracy (P = 0.01) were observed: testing accuracy peaked 4-8 hours post-dose and tapered ~16 hours post dose. In 28/63 instances with low Cavg TT throughout the study a normal 2 hour serum TT level was observed. The average percentage (across all days) of discordant results between Cavg (<300 ng/dL [<10.4 nmol/L]) and single serum TT measurements (300-1050 ng/dL [10.4-36.4 nmol/L]) declined with increasing time from dose application (44% at 2 hours, 38% at 4 hours, 22% at 8 hours, 3% at 16 hours). CONCLUSIONS: Reliance on a single serum testosterone measurement to determine the need for dose adjustment of testosterone topical solution 2% may lead clinicians to change the dose unnecessarily, or alternatively, not increase the dose when necessary. The results reported here are limited to testosterone topical solution 2% and may not be applicable to other topical agents. PMID- 26549706 TI - The status of modeled claims. AB - The only acceptable modeled claims for costs and outcomes are those that are testable and can be validated in a timeframe that is acceptable to a formulary committee. This issue provides four papers which explore the methodological issues in validation, the UK experience with NICE, the questions a formulary committee should ask of modeled claims, and the role of Big Data in validating modeled claims. PMID- 26549707 TI - Nilotinib reduced the viability of human ovarian cancer cells via mitochondria dependent apoptosis, independent of JNK activation. AB - Nilotinib (AMN) induces apoptosis in various cancer cells; however the effect of AMN on human ovarian cancer cells is still unclear. A reduction in cell viability associated with the occurrence of apoptotic characteristics was observed in human SKOV-3 ovarian cancer cells under AMN but not sorafenib (SORA) or imatinib (STI) stimulation. Activation of apoptotic pathway including increased caspase (Casp)-3 and poly(ADP-ribose) polymerase 1 (PARP1) protein cleavage by AMN was detected with disrupted mitochondrial membrane potential (MMP) accompanied by decreased Bcl-2 protein and increased cytosolic cytochrome (Cyt) c/cleaved Casp-9 protein expressions was found, and AMN-induced cell death was inhibited by peptidyl Casp inhibitors, VAD, DEVD and LEHD. Increased phosphorylated c-Jun N-terminal kinase (JNK) protein expression was detected in AMN- but not SORA- or STI-treated SKOV-3 cells, and the JNK inhibitors, SP600125 and JNKI, showed slight but significant enhancement of AMN-induced cell death in SKOV-3 cells. The intracellular peroxide level was elevated by AMN and H2O2, and N-acetylcysteine (NAC) prevented H2O2- but not AMN-induced peroxide production and apoptosis in SKOV-3 cells. AMN induction of apoptosis with increased intracellular peroxide production and JNK protein phosphorylation was also identified in human A2780 ovarian cancer cells, cisplatin-resistant A2780CP cells, and clear ES-2 cells. The evidence supporting AMN effectively reducing the viability of human ovarian cancer cells via mitochondrion-dependent apoptosis is provided. PMID- 26549708 TI - A field pilot-scale study of biological treatment of heavy oil-produced water by biological filter with airlift aeration and hydrolytic acidification system. AB - Heavy oil-produced water (HOPW) is a by-product during heavy oil exploitation and can cause serious environmental pollution if discharged without adequate treatment. Commercial biochemical treatment units are important parts of HOPW treatment processes, but many are not in stable operation because of the toxic and refractory substances, salt, present. Therefore, pilot-scale experiments were conducted to evaluate the performance of hydrolytic acidification-biological filter with airlift aeration (HA-BFAA), a novel HOPW treatment system. Four strains isolated from oily sludge were used for bioaugmentation to enhance the biodegradation of organic pollutants. The isolated bacteria were evaluated using 3-day biochemical oxygen demand, oil, dodecyl benzene sulfonic acid, and chemical oxygen demand (COD) removals as evaluation indices. Bioaugmentation enhanced the COD removal by 43.5 mg/L under a volume load of 0.249 kg COD/m(3) day and hydraulic retention time of 33.6 h. The effluent COD was 70.9 mg/L and the corresponding COD removal was 75.0 %. The optimum volumetric air-to-water ratio was below 10. The removal ratios of the total extractable organic pollutants, alkanes, and poly-aromatic hydrocarbons were 71.1, 94.4, and 94.0 %, respectively. Results demonstrated that HA-BFAA was an excellent HOPW treatment system. PMID- 26549709 TI - Cs-137 in milk, vegetation, soil, and water near the former Soviet Union's Semipalatinsk Nuclear Test Site. AB - The present study was carried out to evaluate Cs-137 activity concentration in soil, water, vegetation, and cow's milk at 10 locations within three regions (Abai, Ayaguz, and Urdzhar) to the southeast of the Semipalatinsk Nuclear Test Site (SNTS) in Kazakhstan. Cs-137 activity concentrations, determined using a pure Ge gamma-ray spectrometer, showed that, all samples collected did not exceed the National maximum allowable limits of 10,000 Bq/kg for soil, 100 Bq/kg for cow's milk, 74 Bq/kg for vegetation, and 11 Bq/kg for water. Cs-137 is, therefore, not considered a health hazard in these regions. The highest levels of contamination were found in the Abai region, where the highest activity concentration of Cs-137 was 18.0 +/- 1.0 Bq/kg in soil, 7.60 +/- 0.31 Bq/kg in cow's milk, 4.00 +/- 0.14 Bq/kg in the vegetation, and 3.00 +/- 0.24 Bq/kg in water. The lowest levels were measured within the Urdzhar region, where 4.00 +/- 0.14 Bq/kg was found in the soil, 0.30 +/- 0.02 Bq/kg in the cow's milk, 1.00 +/- 0.03 Bq/kg in the vegetation, and 0.20 +/- 0.02 Bq/kg in the water. PMID- 26549710 TI - Estimates of long-term water total phosphorus (TP) concentrations in three large shallow lakes in the Yangtze River basin, China. AB - The shallow lakes in the eastern China developed on alluvial plains with high nutrient sediments, and most overflow into the Yangtze River with short hydraulic residence times, whereas they become eutrophic over long time periods. Assuming strong responses to hydrogeological changes in the basin, we attempted to determine the dynamic eutrophication history of these lakes. Although evaluation models for internal total phosphorus (TP) loading are widely used for deep lakes in Europe and North America, the accuracy of these models for shallow lakes that have smaller water volumes controlled by the geometrical morphology and greater basin area of alluvial plains is unknown. To describe the magnitude of changes in velocity of trophic state for the studied shallow lakes, we first evaluated the P retention model in relation to the major forces driving lake morphology, basin climate, and external discharge and then used the model to estimate changes in TP in three large shallow lakes (Taihu, Chao, and Poyang) over 60 years (1950-2009 AD). The observed levels of TP were verified against the relative error of the three lakes (<6.43 %) and Nash-Sutcliffe coefficients (0.67-0.75). The results showed that the predicted TP concentrations largely increased with hydraulic residence time, especially in extreme drought years, with a generally rising trend in trophic status. The simulated trophic state index showed that lakes Taihu and Poyang became eutrophic in the 1990s, whereas Lake Chao became eutrophic in the 1980s; lakes Taihu and Chao ultimately became hypereutrophic in the 2000s. The analysis suggested that the tropic status of the shallow lakes was affected by both the hydroclimate and geological sedimentation of the Yangtze River basin. This work will contribute to the development of an internal P loading model for further evaluating trophic states. PMID- 26549711 TI - Highly Conductive Graphene/Ag Hybrid Fibers for Flexible Fiber-Type Transistors. AB - Mechanically robust, flexible, and electrically conductive textiles are highly suitable for use in wearable electronic applications. In this study, highly conductive and flexible graphene/Ag hybrid fibers were prepared and used as electrodes for planar and fiber-type transistors. The graphene/Ag hybrid fibers were fabricated by the wet-spinning/drawing of giant graphene oxide and subsequent functionalization with Ag nanoparticles. The graphene/Ag hybrid fibers exhibited record-high electrical conductivity of up to 15,800 S cm(-1). As the graphene/Ag hybrid fibers can be easily cut and placed onto flexible substrates by simply gluing or stitching, ion gel-gated planar transistors were fabricated by using the hybrid fibers as source, drain, and gate electrodes. Finally, fiber type transistors were constructed by embedding the graphene/Ag hybrid fiber electrodes onto conventional polyurethane monofilaments, which exhibited excellent flexibility (highly bendable and rollable properties), high electrical performance (MUh = 15.6 cm(2) V(-1) s(-1), Ion/Ioff > 10(4)), and outstanding device performance stability (stable after 1,000 cycles of bending tests and being exposed for 30 days to ambient conditions). We believe that our simple methods for the fabrication of graphene/Ag hybrid fiber electrodes for use in fiber-type transistors can potentially be applied to the development all-organic wearable devices. PMID- 26549712 TI - Cultivating microbial dark matter in benzene-degrading methanogenic consortia. AB - The microbes responsible for anaerobic benzene biodegradation remain poorly characterized. In this study, we identified and quantified microbial populations in a series of 16 distinct methanogenic, benzene-degrading enrichment cultures using a combination of traditional 16S rRNA clone libraries (four cultures), pyrotag 16S rRNA amplicon sequencing (11 cultures), metagenome sequencing (1 culture) and quantitative polymerase chain reaction (qPCR; 12 cultures). An operational taxonomic unit (OTU) from the Deltaproteobacteria designated ORM2 that is only 84% to 86% similar to Syntrophus or Desulfobacterium spp. was consistently identified in all enrichment cultures, and typically comprised more than half of the bacterial sequences. In addition to ORM2, a sequence belonging to Parcubacteria (candidate division OD1) identified from the metagenome data was the only other OTU common to all the cultures surveyed. Culture transfers (1% and 0.1%) were made in the presence and absence of benzene, and the abundance of ORM2, OD1 and other OTUs was tracked over 415 days using qPCR. ORM2 sequence abundance increased only when benzene was present, while the abundance of OD1 and other OTUs increased even in the absence of benzene. Deltaproteobacterium ORM2 is unequivocally the benzene-metabolizing population. This study also hints at laboratory cultivation conditions for a member of the widely distributed yet uncultivated Parcubacteria (OD1). PMID- 26549713 TI - Making sense of it: intensive care patients' phenomenological accounts of story construction. AB - BACKGROUND: Patients entering intensive care encounter physical and psychological stress that may lead to psychological morbidity such as depression, anxiety and post-traumatic stress. It has been suggested that constructing a story may assist psychological recovery. However, this has been minimally investigated in intensive care patients. AIM: The aim of this article is to examine the process of story construction in people's phenomenological accounts of being a patient in the technological environment of intensive care. STUDY DESIGN: The study design was informed by Heideggerian phenomenology. METHODS: Semi-structured interviews were conducted with 19 patients who had been in intensive care for at least 4 days. Interviews were digitally recorded, transcribed and analysed utilizing Van Manen's framework for thematic analysis. FINDINGS: Making sense of their experiences in an intensive care unit appeared to be fundamental to story construction. Themes that arose were 'why am I here?', 'filling in the gaps', 'sorting the real from the unreal' and 'searching for familiarity'. These themes describe how participants sought temporal and causal coherence in order to construct their integrated and understandable story. Families appeared to play a critical role in helping participants fill in the gaps, sorting the real from the unreal and their subsequent psychological recovery. CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: The importance of early support from health care professionals to facilitate patients' story construction is highlighted. The study also emphasizes the role families play in supporting patients while they make sense of their experiences and the associated psychological recovery process. Further research to evaluate methods of facilitating story construction, such as nurse led debriefing and patient diaries, is recommended. In addition, an investigation of families' perceptions of their role in assisting patients construct their story may facilitate the development of strategies by health care professionals to effectively support families in their role. PMID- 26549715 TI - Application of linear pH gradients for the modeling of ion exchange chromatography: Separation of monoclonal antibody monomer from aggregates. AB - The mobile phase pH is a key parameter of every ion exchange chromatography process. However, mechanistic insights into the pH influence on the ion exchange chromatography equilibrium are rare. This work describes a mechanistic model capturing salt and pH influence in ion exchange chromatography. The pH dependence of the characteristic protein charge and the equilibrium constant is introduced to the steric mass action model based on a protein net charge model considering the number of amino acids interacting with the stationary phase. This allows the description of the adsorption equilibrium of the chromatographed proteins as a function of pH. The model parameters were determined for a monoclonal antibody monomer, dimer, and a higher aggregated species based on a manageable set of pH gradient experiments. Without further modification of the model parameters the transfer to salt gradient elution at fixed pH is demonstrated. A lumped rate model was used to predict the separation of the monoclonal antibody monomer/aggregate mixture in pH gradient elution and for a pH step elution procedure-also at increased protein loadings up to 48 g/L packed resin. The presented model combines both salt and pH influence and may be useful for the development and deeper understanding of an ion exchange chromatography separation. PMID- 26549714 TI - Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. AB - BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6 week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to 0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of life scores, or NT-proBNP levels. CONCLUSIONS: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.). PMID- 26549716 TI - [3D Printer and Its Impact on Neurosurgery]. PMID- 26549717 TI - [Responding to Arterial Perforation during Endovascular Neurosurgery]. AB - During endovascular neurosurgery, various devices, such as catheters, are passed through the intracranial arteries to access target vessels; the arteries can thereby be perforated. Even though such incidents are serious and should be dealt with appropriately, few case reports or standard procedures have been published. Herein, we report two cases of arterial perforation that occurred recently in our hospital. In the first case, the patient had been treated preoperatively using feeder occlusion of an arteriovenous malformation; the microcatheter perforated the feeder, which branched from the middle cerebral artery. The feeder and perforation site were occluded by injection of n-butyl 2-cyanoacrylate (NBCA) through the same microcatheter, and complete hemostasis was thereby achieved. The second case occurred during an embolization of the middle meningeal artery (MMA) to treat a refractory chronic subdural hematoma;the microcatheter perforated a branch of the MMA. Both the perforation and the artery were embolized using platinum coils and by injecting NBCA, and hemostasis was achieved. Considering the anatomical and pathological properties of the injured vessels, favorable results were achieved with appropriate intervention. PMID- 26549718 TI - [Computed Tomography Criteria for Mild Head Trauma in Childhood: A Retrospective Study]. AB - We retrospectively investigated 459 computed tomography (CT) scans of head injuries in children who were 7 years of age or younger that we experienced at our institute from 2008 to 2014, and investigated whether or not the algorithm created by the Pediatric Emergency Care Applied Research Network and the guidelines by the National Institute for Health and Care Excellence, which are the standards for CT scans of head injuries in infants, are adequate. As a result, all 12 cases that required surgery or resulted in serious brain damage fell into the category for CT recommendation according to both standards. Although several cases that fell into the category for consideration of CT involved intracranial lesions, all such cases were mild. There were some cases with negligible CT findings that were excluded by both standards. We believe that adapting these standards is significant for reducing the degree to which children are exposed to irradiation. PMID- 26549719 TI - [Stent-in-Stenting for In-Stent Stenosis after Carotid Artery Stenting:A Report of 2 Cases]. AB - Standard strategy for the treatment of subacute in-stent stenosis after carotid artery stenting remains controversial. We report the successful application of stent-in-stenting in 2 patients with subacute in-stent stenosis of the internal carotid arteries (ICA). The postoperative courses of both patients were uneventful, and the patency of the ICA was confirmed at the 2-year follow-up. In this study, medical treatment was not effective, and therefore, stent-in-stenting was used as an alternative treatment for subacute in-stent stenosis. PMID- 26549720 TI - [A Patient with Advanced Gastric Cancer who Underwent Emergency Stenting for Carotid Artery Stenosis]. AB - We report the case of a patient with advanced gastric cancer who underwent emergency stenting for carotid artery stenosis that was causing fluctuating symptoms of cerebral ischemic stroke. A 66-year-old man presented with transient dysarthria and right hemifacial palsy. Examination revealed left internal carotid artery stenosis, as well as anemia caused by advanced gastric cancer. The man was treated on an outpatient basis using antiplatelet medication and anti-cancer therapy. Two months later, he developed recurrent ischemic stroke;because of this progression, a stent was placed in the carotid artery. After surgery, the cerebral ischemia resolved and did not recur before his death 6 months later. In conclusion, surgical intervention is a viable treatment option for internal carotid artery stenosis in cancer patients whose general health status is good. PMID- 26549721 TI - [Three Cases of Moyamoya Disease with a History of Kawasaki Disease]. AB - Here, we report three cases of moyamoya disease with a history of Kawasaki disease. A 33-year-old man was found to have stenotic lesions of the internal carotid arteries(ICAs)on both sides at a nearby hospital where he visited complaining of headache and lisping. He had received immunoglobulin therapy for Kawasaki disease at the ages of 1, 2, and 6 years. MRI showed only a chronic ischemic lesion in the white matter. Angiography showed occlusion at the terminal portion of the ICAs on both sides. He was diagnosed with moyamoya disease, but as he had no symptoms and preserved cerebral blood flow (CBF), he was kept under observation. An 8-year-old boy was diagnosed with moyamoya disease and underwent right encephaloduroarteriosynangiosis at a nearby hospital. He had received immunoglobulin therapy for Kawasaki disease at the age of 1 year. His ischemic symptoms worsened. Although MRI detected no apparent ischemic lesion, angiography revealed severe stenosis at the terminal portions of the ICAs on both sides, and 123I-IMP SPECT showed CBF impairment. Bilateral direct bypass was performed. His father was subsequently also diagnosed with moyamoya disease. A 4-year-old girl with epilepsy was diagnosed with moyamoya disease at a nearby hospital. She had been treated with aspirin for Kawasaki disease at the age of 1 year. MRI detected no remarkable ischemic lesions, but angiography revealed mild stenosis at the terminal portions of the ICAs on both sides. Five months later, her ischemic symptoms were worsening with progressing stenotic lesions, and she underwent bilateral direct bypass. PMID- 26549722 TI - [A Case of Percutaneous Transluminal Angioplasty and Stenting for Dacron Bypass Graft Stenosis with Cerebral Infarction]. AB - A 62-year-old man presented to the emergency room with mild dysarthria and right motor weakness. The patient was diagnosed with aortic dissection (DeBakey type III) in the cardiovascular department of our institution two years ago and was then treated with left carotid-bilateral subclavian bypass with collagen-seated Dacron graft followed by thoracic endovascular aortic repair (TEVER) with stent graft placement. Magnetic resonance imaging on admission showed cerebral infarction with left proximal middle cerebral artery occlusion in the left cerebral hemisphere. Three-dimensional computed tomography angiography (3D-CTA) demonstrated a stenotic lesion at the anastomosis of the right subclavian artery and the bypass graft. It also showed the partial left common carotid artery, suggestive of an endoleak in the thoracic stent graft. The patient was diagnosed with artery-to-artery embolism due to bypass graft stenosis or endoleak in the thoracic stent graft and was treated with conservative therapy. He gradually recovered from the neurological deficit and underwent endovascular angioplasty with a balloon-expandable stent for bypass graft stenosis by using the distal balloon protection method and the left proximal common carotid artery occlusion with coils 1 month later. One-year follow-up 3D-CTA showed good patency of the stent in the bypass graft. No recurrence of cerebral infarction was observed during the postoperative course. PMID- 26549724 TI - [Update Knowledge for Brain Tumors (1) Epidemiology and Registry of Brain Tumors]. PMID- 26549723 TI - [Spontaneous Dilatation of Carotid Artery Stents Three Months after the Procedure, without the Need for Post-CAS Balloon Dilatation]. AB - OBJECTIVE: The aim of this retrospective study was to investigate whether the radial force of a self-expandable stent alone is sufficient to dilate an atherosclerotic carotid artery without the need for post-carotid artery stenting (CAS) balloon dilatation (PCasBD). METHODS: We included in our analysis patients who had undergone (1) elective CAS without PCasBD from January 2012 to March 2014, and (2) follow-up conventional angiography 3 months after CAS. We recorded the patients' baseline characteristics and stent types (open-cell [OP] or closed cell [CL]). Using the minimum width on the lateral projection, stent diameters (SDs) were measured at the site both post-operatively and 3 months after CAS. RESULTS: Fifty-eight lesions in 55 patients were analyzed. The average age of the patients was 74.4 years;the median SD immediately after CAS was 3.27 mm (interquartile range: 3.09-3.64 mm), while after 3 months it was 3.97 mm (3.58 4.25 mm), a significant increase (p<0.0001). In Regarding OP stents specifically (n=18), the median SD increased from 3.59 to 4.05 mm, while the median diameter of CL stents (n=44) increased from 3.22 to 3.83 mm. The median diameter of OP stents was larger than that of CL stents at both time points (p<0.05), whereas the expansion rate of CL stents was higher. CONCLUSION: All stents had spontaneously dilated by 10% to 20% without PCasBD. The diameter of OP stents was larger than that of CL stents, both immediately and 3 months after CAS.(Received:April 1, 2015, Accepted:August 3, 2015). PMID- 26549725 TI - miR-21: A gene of dual regulation in breast cancer. AB - Breast cancer is characterized by an elevated capacity for tumor invasion and lymph node metastasis, but the cause remains to be determined. Recent studies suggest that microRNAs (miRNAs) can regulate the evolution of malignant behavior by regulating multiple target genes. A key oncomir in carcinogenesis is miR-21, which is consistently upregulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and searched for miR-21 targets.Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-21 expression by quantificational real-time polymerase chain reaction (qRT-PCR), followed by analysis of the correlation between gonad hormone indices in peripheral blood and miR-21 expression in cancerous tissues from the same patients. Cell proliferation, colony formation, migration and invasion were then examined to determine the role of miR-21 in regulating breast cancer cells. Finally, western blotting was performed to determine if miR-21 regulated expression of signal transducers and activators of transcription 3 (STAT3), and assays of cell proliferation, colony formation, migration and invasion were performed to examine the role of STAT3 in regulation of breast cancer cells. We found that expression of miR-21 increased from normal through benign to cancerous breast tissues. Enhanced miR-21 expression was associated with serum levels of follicle-stimulating hormone, estradiol, beta-human chorionic gonadotropin, testosterone and prolactin in patients with breast cancer. Furthermore, cell proliferation, colony formation, migration and invasion were increased after overexpression of miR-21 in breast cancer cells and reduced by miR-21 suppression. In addition, we identified a putative miR-21 binding site in the 3' untranslated region of the STAT3 gene using an online bioinformatical tool. We found that protein expression of STAT3 was significantly downregulated when breast cancer cells were transfected with miR-21 mimics, and was significantly upregulated in breast cancer cells transfected with a miR-21 inhibitor. Finally, we found that cell proliferation, colony formation, migration and invasion were decreased by treatment with 2.5 nM of Stattic, an inhibitor of STAT3 activation. Our data suggest that miR-21 expression is increased in breast cancer and plays an important role as a tumor gene by targeting STAT3, which may act as a double response controller in breast cancer. PMID- 26549726 TI - Minimum oxygen flow needed for vital support during simulated post cardiorespiratory arrest resuscitation. AB - According to the ERC and the AHA guidelines, FiO2 should be titrated to achieve an O2Sat >= 94%. The aim of this study was to determine the minimum oxygen flow and time needed to reach an FiO2 of 0.32 and 0.80 during post-cardiac arrest care. An experimental analysis was performed that consisted of a simulated post cardiac arrest situation. Different resuscitators were tested and connected to an artificial lung: Mark IV, SPUR II, Revivator Res-Q, O-TWO. The oxygen flow levels tested were 2, 5, 10 and 15 lpm. Bonferroni and Mann-Whitney U tests were used. An FiO2 of 0.32 or more was obtained using any of the oxygen flow and resuscitators. Only the Mark IV achieved an FiO2 of 0.80 after a minimum of 75s ventilating with 2 or 5 lpm. Clinical and statistical differences (P<.05) were found: at 15 lpm it took 35s to reach an FiO2 of 0.80 or more for Mark IV (85.6 [0.3]) and Revivator (84.3 [1.5]) compared to 50s for SPUR II (87.1 [6.4]); at 2 lpm, all of the devices reached an FiO2 of >= 0.32 at 30s(Mark IV (34.8 [1.3]), Revivator (35.7 [1.5]) and SPUR II (34.4 [2.1]), except for O-TWO, which took 35s (36.3 [4.3]). Patients could be ventilated with any of the resuscitators using 2 lpm to obtain an FiO2 of 0.32, although possibly O-TWO would be the last option during the first 60s. In order to reach an FiO2 of 0.80, ventilating with 10 lpm should be sufficient, and preferably using Mark IV or Revivator Res-Q. In conclusion, on observing the results of our study, in any possible scenario, it would be advisable to use Revivator Res-Q or Mark IV rather than O-TWO or SPUR II. PMID- 26549727 TI - Letter to the editor: "Immunosuppressive drug therapy--biopharmaceutical challenges and remedies". PMID- 26549728 TI - Improved method of gastrostomy tube replacement using a small-caliber transnasal endoscope. AB - CONCLUSION: Gastrostomy tube replacement using a new approach through the abdominal-wall stoma with a small-caliber trans-nasal endoscope is feasible, fast, and safe compared with the trans-oral approach. OBJECTIVES: To evaluate the feasibility of a new technique using a trans-nasal endoscope for gastrostomy tube replacement. METHODS: Between June 2005 and December 2013 in the Peking University Third Hospital, 69 patients underwent gastrostomy tube replacement using the trans-oral approach (conventional method) or a small-caliber trans nasal endoscope inserted through the abdominal-wall stoma (new method). A retrospective review was performed of the medical records of those patients, including demography and information about the surgical procedure and any complications. Patients were classified into the conventional group and the new method group. Descriptive statistics for all continuous variables were mean +/- standard deviation and for categorical variables were number and percentage. RESULTS: Gastrostomy tube replacement was achieved in 69 of 69 cases (100%); 23 of these procedures were performed using the new method. The surgery time with the conventional method (8.3 +/- 2.0 min) was significantly longer than with the new method (6.0 +/- 0.9 min, p < 0.001). With the conventional method, there was one patient (2%) with post-operative fever and skin infection; no complications occurred with the new method. PMID- 26549729 TI - Porous nanoarchitectures of spinel-type transition metal oxides for electrochemical energy storage systems. AB - Transition metal oxides possessing two kinds of metals (denoted as AxB3-xO4, which is generally defined as a spinel structure; A, B = Co, Ni, Zn, Mn, Fe, etc.), with stoichiometric or even non-stoichiometric compositions, have recently attracted great interest in electrochemical energy storage systems (ESSs). The spinel-type transition metal oxides exhibit outstanding electrochemical activity and stability, and thus, they can play a key role in realising cost-effective and environmentally friendly ESSs. Moreover, porous nanoarchitectures can offer a large number of electrochemically active sites and, at the same time, facilitate transport of charge carriers (electrons and ions) during energy storage reactions. In the design of spinel-type transition metal oxides for energy storage applications, therefore, nanostructural engineering is one of the most essential approaches to achieving high electrochemical performance in ESSs. In this perspective, we introduce spinel-type transition metal oxides with various transition metals and present recent research advances in material design of spinel-type transition metal oxides with tunable architectures (shape, porosity, and size) and compositions on the micro- and nano-scale. Furthermore, their technological applications as electrode materials for next-generation ESSs, including metal-air batteries, lithium-ion batteries, and supercapacitors, are discussed. PMID- 26549730 TI - Factor Structure and Gender Stability of the Brazilian Version of the Pornography Consumption Inventory. AB - There are a few instruments available to measure pornograhy consumption-related constructs, and this lack of instruments can compromise the validity of research findings. The Pornography Consumption Inventory (PCI) assesses four motivations for pornography consumption, and it has been validated in hypersexual men and medical students. However, whether the psychometric properties of this instrument are comparable across genders remains unclear. Multigroup confirmatory factor analysis (MGCFA) was used to verify the invariance of the structure of the PCI across male (100) and female (105) university students. The confirmatory factor analysis (CFA) for each group showed a reasonably good fit of the data to the four-factor model. The MGCFA model included only factor loadings constrained to be equal between both genders (DeltaCFI < 0.01 and p > 0.05). However, the DeltaCFI did not support a strong and strict factorial invariance, DeltaCFI > 0.01. Although both genders seemed to agree with the conceptualization of pornography and motivations for consuming it, the PCI was not gender-invariant, as men showed a stronger degree of motivation to consume pornographic material than women did. The implications of these findings regarding the measurement of motivations for pornography use are outlined. PMID- 26549731 TI - Liposome Membrane as a Platform for the L-Pro-Catalyzed Michael Addition of trans beta-Nitrostyrene and Acetone. AB - Herein, we show that the L-proline (L-Pro)-catalyzed Michael addition of trans beta-nitrostyrene and acetone can proceed in "water" using liposome membranes and that the membrane fluidity and polarity are major controlling factors for this reaction. The highest conversion and rate constant of the reaction within the liposomes was achieved with the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-3-trimethylammoniumpropane (DPTAP) system. The catalytic activity of L-Pro in the liposome suspension was found to be comparable to that in a DMSO system. The reaction rate constant was found to be controlled by both the phase state of the liposome membrane and the surface charge on the membrane. Greater enantioselectivity was achieved in the presence of the liposomes than in DMSO solution, with corresponding enantiomeric excess values of 97.6% for the DOPC/DPTAP liposome system and 10% in DMSO. The hydrophobic region of the liposome membrane, which is a relatively stable self-organizing system, can serve as an effective "platform" for molecular recognition and selective conversion in aqueous media. PMID- 26549732 TI - Tunable porosity of 3D-networks with germanium nodes. AB - Eight hyper cross-linked polymers based on tetrakis(4-ethynylphenyl)germanium and tetrakis(4-ethynylphenyl)methane are presented. After investigation of their N2 adsorption properties at 77 K, the porosity of the germanium-based porous organic polymers (POPs) was modulated under acidic conditions, offering an easy and direct way, in a single step, to tune the adsorption properties. PMID- 26549733 TI - Controlling Selectivity by Controlling the Path of Trajectories. AB - Consideration of the role of dynamic trajectories in [1,2]- and [2,3]-sigmatropic rearrangements suggests a counterintuitive approach to controlling the selectivity. In our hypothesis, [2,3] selectivity can be promoted by reaction conditions that thermodynamically disfavor the [2,3] rearrangement step and thereby make the transition state later. The application of this idea has led to a successful prescription for dictating the selectivity in Stevens/Sommelet Hauser rearrangements of ammonium ylides. A combination of kinetic isotope effects, crossover experiments, and computational dynamic trajectories support the idea that the selectivity is controlled through control of the path of trajectories. PMID- 26549734 TI - A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice. AB - AIM: The main pathophysiology of abdominal aortic aneurysm (AAA) considerably overlaps with that of atherosclerosis. We reported that incretins [glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP)] or a dipeptidyl peptidase-4 inhibitor (DPP-4I) suppressed atherosclerosis in apolipoprotein E-null (Apoe-/-) mice. Here we investigated the effects of incretin-related agents on AAA in a mouse model. METHODS: Apoe-/- mice maintained on an atherogenic diet were subcutaneously infused with saline, Ang II (2000 ng/kg/min), Ang II, and native GLP-1 (2.16 nmol/kg/day) or Ang II and native GIP (25 nmol/kg/day) for 4 weeks. DPP-4I (MK0626, 6 mg/kg/day) was provided in the diet to the Ang II-infused mice with or without incretin receptor antagonists [(Pro3) GIP and exendin (9-39)]. RESULTS: AAA occurred in 70% of the animals receiving Ang II. DPP-4I reduced this rate to 40% and significantly suppressed AAA dilatation, fibrosis, and thrombosis. In contrast, incretins failed to attenuate AAA. Incretin receptor blockers did not reverse the suppressive effects of DPP-4I on AAA. In the aorta, DPP-4I significantly reduced the expression of Interleukin-1beta and increased that of tissue inhibitor of metalloproteinase (TIMP)-2. In addition, DPP-4I increased the ratio of TIMP-2 to matrix metalloproteinases-9. CONCLUSIONS: DPP-4I, MK0626, but not native incretins has protective effects against AAA in Ang II-infused Apoe-/- mice via suppression of inflammation, proteolysis, and fibrosis in the aortic wall. PMID- 26549735 TI - Capturing VE-Cadherin-Positive Endothelial Progenitor Cells for in-stent Vascular Repair. PMID- 26549738 TI - High-Speed Multipass Coulter Counter with Ultrahigh Resolution. AB - Coulter counters measure the size of particles in solution by passing them through an orifice and measuring a resistive pulse, i.e., a drop in the ionic current flowing between two electrodes placed on either side of the orifice. The magnitude of the pulse gives information on the size of the particle; however, resolution is limited by variability in the path of the translocation, due to the Brownian motion of the particle. We present a simple yet powerful modified Coulter counter that uses programmable data acquisition hardware to switch the voltage after sensing the resistive pulse of a nanoparticle passing through the orifice of a nanopipet. Switching the voltage reverses the direction of the driving force on the particle and, when this detect-switch cycle is repeated, allows us to pass an individual nanoparticle through the orifice thousands of times. By measuring individual particles more than 100 times per second we rapidly determine the distribution of the resistive pulses for each particle, which allows us to accurately determine the mean pulse amplitude and deliver considerably improved size resolution over a conventional Coulter counter. We show that single polystyrene nanoparticles can be shuttled back and forth and monitored for minutes, leading to a precisely determined mean blocking current equating to sub-angstrom size resolution. PMID- 26549737 TI - Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. AB - Gastric cancer (GC) is the second most common cause of cancer-associated mortality worldwide. Previous studies suggest that mitogen-activated protein kinase kinase kinase kinase isoform 4 (MAP4K4) is involved in cancer cell growth, apoptosis and migration. In the present study, bioinformatics analysis and reverse transcription-quantitative polymerase chain reaction were performed to determine if MAP4K4 was overexpressed in GC. The knockdown of MAP4K4 by RNA interference in GC cells markedly inhibited cell proliferation, which may be mediated by cell cycle arrest in the G1 phase. The silencing of MAP4K4 also induced cell apoptosis by increasing the ratio of Bax/Bcl-2. In addition, Notch signaling was markedly reduced by MAP4K4 silencing. The results of the present study suggested that inhibition of MAP4K4 may be a therapeutic strategy for GC. PMID- 26549736 TI - MiR-150 impairs inflammatory cytokine production by targeting ARRB-2 after blocking CD28/B7 costimulatory pathway. AB - MiR-150, a major modulator negatively regulating the development and differentiation of various immune cells, is widely involved in orchestrating inflammation. In transplantation immunity, miR-150 can effectively induce immune tolerance, although the underlying mechanisms have not been fully elucidated. In the current study, we found that miR-150 is elevated after blocking CD28/B7 co stimulatory signaling pathway and impaired IL-2 production by targeting ARRB2. Further investigation suggested that miR-150 not only repressed the level of ARRB2/PDE4 directly but also prevented AKT/ARRB2/PDE4 trimer recruitment into the lipid raft by inhibiting the activities of PI3K and AKT through the cAMP-PKA-Csk signaling pathway. This leads to the interruption of cAMP degradation and subsequently results in inhibition of the NF-kB pathway and reduced production of both IL-2 and TNF. In conclusion, our study demonstrated that miR-150 can effectively prevent CD28/B7 co-stimulatory signaling transduction, decrease production of inflammatory cytokines, such as IL-2 and TNF, and elicit the induction of immune tolerance. Therefore, miR-150 could become a novel potential therapeutic target in transplantation immunology. PMID- 26549739 TI - Searching photodynamic activity in honey. PMID- 26549740 TI - Attachment and prejudice: The mediating role of empathy. AB - In two studies, we examined the novel hypothesis that empathy is a mechanism through which the relationship between attachment patterns and prejudice can be explained. Study 1 examined primed attachment security (vs. neutral prime), empathy, and prejudice towards immigrants. Study 2 examined primed attachment patterns (secure, avoidant, anxious), empathy subscales (perspective taking, empathic concern, personal distress), and prejudice towards Muslims. Across both studies, empathy mediated the relationship between primed attachment security and low prejudice levels. The findings suggest that enhancing felt security and empathic skills in individuals high in attachment-avoidance may lead to reduced prejudice. PMID- 26549741 TI - Epigenetic stimulation of polyketide production in Chaetomium cancroideum by an NAD(+)-dependent HDAC inhibitor. AB - Exposure of the fungus Chaetomium cancroideum to an NAD(+)-dependent HDAC inhibitor, nicotinamide, enhanced the production of aromatic and branched aliphatic polyketides, which allowed us to isolate new secondary metabolites, chaetophenol G and cancrolides A and B. Their structures were determined using spectroscopic analyses, and their absolute configuration was elucidated by electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and chemical transformations. Biosynthesis of the branched aliphatic polyketide skeletons in cancrolides A and B was evidenced by conducting a feeding experiment using compounds labeled with a (13)C stable isotope. PMID- 26549742 TI - Paving the Way to Novel Phosphorus-Based Architectures: A Noncatalyzed Protocol to Access Six-Membered Heterocycles. AB - Phosphorus-based heterocycles provide access to materials with properties that are inaccessible from all-carbon architectures. The unique hybridization of phosphorus gives rise to electron-accepting capacities, a large variety of coordination reactions, and the possibility of controlling the electronic properties through phosphorus postfunctionalization. Herein, we describe a new noncatalyzed synthetic protocol to prepare fused six-membered phosphorus heterocycles. In particular, we report the synthesis of novel phosphaphenalenes. These fused systems exhibit the benefits of both five- and six-membered phosphorus heterocycles and enable a series of versatile postfunctionalization reactions. This work thus opens up new horizons in the field of conjugated materials. PMID- 26549743 TI - The Pseudomonas aeruginosa AmrZ C-terminal domain mediates tetramerization and is required for its activator and repressor functions. AB - Pseudomonas aeruginosa is an important bacterial opportunistic pathogen, presenting a significant threat towards individuals with underlying diseases such as cystic fibrosis. The transcription factor AmrZ regulates expression of multiple P. aeruginosa virulence factors. AmrZ belongs to the ribbon-helix-helix protein superfamily, in which many members function as dimers, yet others form higher order oligomers. In this study, four independent approaches were undertaken and demonstrated that the primary AmrZ form in solution is tetrameric. Deletion of the AmrZ C-terminal domain leads to loss of tetramerization and reduced DNA binding to both activated and repressed target promoters. Additionally, the C-terminal domain is essential for efficient AmrZ-mediated activation and repression of its targets. PMID- 26549744 TI - Is it me? Verbal self-monitoring neural network and clinical insight in schizophrenia. AB - Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia. PMID- 26549745 TI - Psychometric Properties of the Asthma Symptom Diary (ASD), a Diary for Use in Clinical Trials of Persistent Asthma. AB - BACKGROUND: No currently available asthma symptom diary has sufficient validation to be recommended for use as a core asthma outcome measure. OBJECTIVE: The objective of this study was to provide validation data for the 10-item asthma symptom diary (ASD). METHODS: Data were collected in a 4-week prospective, observational study. Subjects completed 3 study visits, completing the ASD twice daily at home for 28 days. Psychometric properties in terms of dimensionality, reliability, validity, and responsiveness were assessed. RESULTS: Data from 276 subjects were analyzed; mean age was 42.9 (standard deviation [SD] = 16.4) years, mean asthma duration was 23.3 (SD = 16.8) years, and 69.6% were female. Confirmatory factor and Rasch analysis supported the ASD as unidimensional and adequately measuring the spectrum of asthma symptom severity. High Cronbach's alpha (0.94) and intraclass correlation coefficients (0.89-0.95) supported reliability. A high correlation between the 7-day average ASD score and the Asthma Control Questionnaire (ACQ) total score (r = 0.75) and Asthma Quality of Life Questionnaire total scores (r = -0.76), and a moderate correlation with FEV1% predicted (r = -0.30) supported convergent validity. Significant differences (P < .001) between groups classified by ACQ scores supported known group validity. The 7-day average ASD scores were responsive to change, with significantly higher score changes (P < .001) in responders versus nonresponders. Minimally important differences were calculated and found to be in the range of 0.1-0.3. CONCLUSION: Results of this study indicated that the ASD is a reliable and valid asthma symptom measure for use in adult and adolescent asthma patients to evaluate the effect of treatment on asthma in clinical trials. PMID- 26549746 TI - Individual honey bee (Apis cerana) foragers adjust their fuel load to match variability in forage reward. AB - Animals may adjust their behavior according to their perception of risk. Here we show that free-flying honey bee (Apis cerana) foragers mitigate the risk of starvation in the field when foraging on a food source that offers variable rewards by carrying more 'fuel' food on their outward journey. We trained foragers to a feeder located 1.2 km from each of four colonies. On average foragers carried 12.7% greater volume of fuel, equivalent to 30.2% more glucose when foraging on a variable source (a random sequence of 0.5, 1.5 and 2.5 M sucrose solution, average sucrose content 1.5 M) than when forging on a consistent source (constant 1.5 M sucrose solution). Our findings complement an earlier study that showed that foragers decrease their fuel load as they become more familiar with a foraging place. We suggest that honey bee foragers are risk sensitive, and carry more fuel to minimize the risk of starvation in the field when a foraging trip is perceived as being risky, either because the forager is unfamiliar with the foraging site, or because the forage available at a familiar site offers variable rewards. PMID- 26549747 TI - Insulin induces the expression of FGF2 but does not synergize with it during angiogenesis. AB - Cardiovascular and ischemic diseases are often associated with diabetes mellitus and develop due to occlusion of blood vessels leading to the blockage and insufficient blood supply to the target organs. Current therapeutic strategies for treating these pathologies include growth factor-, gene- and stem cell-based therapies. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) have been used in clinical trials to induce blood vessels. On the other hand, increased levels of both these growth factors have been observed with intense insulin therapy in diabetes mellitus patients further leading to increased risk of retinopathy. This suggests the presence of a possible crosstalk between insulin, FGF and VEGF pathways during angiogenesis. In the present work, we report the likely absence of synergistic effect between insulin and FGF-2. This was initially observed at morphological and histological levels using chick embryonic chorioallantoic membrane (CAM) assay and confirmed by analyzing the expression of angiogenesis regulatory genes by semi-quantitative reverse transcriptase PCR (RT-PCR). Absence of combinatorial effect between insulin, FGF 2 and VEGF during angiogenesis was also demonstrated using CAM assay. PMID- 26549748 TI - Convergent evolution of marine mammals is associated with distinct substitutions in common genes. AB - Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection. PMID- 26549750 TI - Euedaphic and hemiedaphic Collembola suffer larger damages than epedaphic species to nitrogen input. AB - Wetlands are commonly limited in available nitrogen. But marshes in the Sanjiang Plain, Northeastern China suffer large amounts of exogenous nitrogen from agriculture fertilization after wetland reclamation. This paper focuses on the ecological effects of a short-term increase of nitrogen input on collembolan communities. Our results show a significant decrease in collembolan abundance and Shannon diversity index, and the abundance of euedaphic and hemiedaphic collembolans decreased faster than epedaphic collembolans. These results indicate that euedaphic or hemiedaphic fauna suffer more biodiversity loss caused by nitrogen deposition than epedaphic fauna and call for more researches on trait based approaches under environmental stress in the future. PMID- 26549749 TI - Microfluidic devices to enrich and isolate circulating tumor cells. AB - Given the potential clinical impact of circulating tumor cells (CTCs) in blood as a clinical biomarker for the diagnosis and prognosis of various cancers, a myriad of detection methods for CTCs have been recently introduced. Among those, a series of microfluidic devices are particularly promising as they uniquely offer micro-scale analytical systems that are highlighted by low consumption of samples and reagents, high flexibility to accommodate other cutting-edge technologies, precise and well-defined flow behaviors, and automation capability, presenting significant advantages over conventional larger scale systems. In this review, we highlight the advantages of microfluidic devices and their potential for translation into CTC detection methods, categorized by miniaturization of bench top analytical instruments, integration capability with nanotechnologies, and in situ or sequential analysis of captured CTCs. This review provides a comprehensive overview of recent advances in CTC detection achieved through application of microfluidic devices and the challenges that these promising technologies must overcome to be clinically impactful. PMID- 26549751 TI - Persistence of detectable insecticidal proteins from Bacillus thuringiensis (Cry) and toxicity after adsorption on contrasting soils. AB - Insecticidal Cry, or Bt, proteins are produced by the soil-endemic bacterium, Bacillus thuringiensis and some genetically modified crops. Their environmental fate depends on interactions with soil. Little is known about the toxicity of adsorbed proteins and the change in toxicity over time. We incubated Cry1Ac and Cry2A in contrasting soils subjected to different treatments to inhibit microbial activity. The toxin was chemically extracted and immunoassayed. Manduca sexta was the target insect for biotests. Extractable toxin decreased during incubation for up to four weeks. Toxicity of Cry1Ac was maintained in the adsorbed state, but lost after 2 weeks incubation at 25 degrees C. The decline in extractable protein and toxicity were much slower at 4 degrees C with no significant effect of soil sterilization. The major driving force for decline may be time-dependent fixation of adsorbed protein, leading to a decrease in the extraction yield in vitro, paralleled by decreasing solubilisation in the larval gut. PMID- 26549752 TI - p53-dependent apoptosis contributes to di-(2-ethylhexyl) phthalate-induced hepatotoxicity. AB - Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread non-occupational human exposure through multiple routes and media. DEHP has various deleterious effects including hepatotoxicity. p53 protein is a central sensor in cell apoptosis. In order to clarify the roles of p53 in DEHP-induced hepatotoxicity, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30 days; BRL cells (rat liver cell line) were treated with DEHP for 24 h after pretreatment with NAC or small interfering RNA (siRNA). Results indicated that after exposure to DEHP, hepatic histological changes such as hepatocyte edema, vacuolation and hepatic sinusoidal dilation, and increased apoptosis index were observed. In the liver, DEHP induced oxidative stress and DNA damage, which activated p53 in vivo and in vitro. Pretreatment with NAC significantly reduced ROS level and p53 expression in BRL cells. The suppressed Mdm2 also contributed to p53 accumulation. Activated p53 mediated hepatocyte apoptosis via the intrinsic mitochondrial pathway, inhibiting anti apoptotic Bcl-2 and Bcl-xL and inducing pro-apoptotic Bax, cytochrome c and caspases. In p53-silenced BRL cells, hepatocyte apoptosis mediated by p53 was attenuated. PCNA protein level was upregulated after p53 gene silencing. However, the Fas/FasL apoptotic pathway did not exhibit activated signs in DEHP-caused hepatotoxicity. Taken together, DEHP-caused oxidative stress and Mdm2 downregulation contribute to p53 activation. The p53-dependent apoptotic pathway plays critical and indispensable roles in DEHP-induced hepatotoxicity, while the Fas/FasL pathway does not involve in this molecular event. PMID- 26549753 TI - Effect assessment of engineered nanoparticles in solid media - Current insight and the way forward. AB - Engineered Nanoparticles (ENPs) present novel/added challenges to the established effect assessment modus operandi, requiring an update of used methods. ENPs are dimensionally and physically different from conventional chemicals, which imply that the metrics with which we relate effect and the type of effect responses are different from that of the conventional approach. Effects on organisms are often preceded by changes on the sub-organismal level (cell, genes), dedicated tools have vast potential to detect earlier (and link to) effects on higher levels of organization. High-throughput screening (HTS) is rapid, cost-effective and specific. One way forward is to link HTS to population outcomes, targeting a systems toxicology approach. Although the benefits of integrating various levels of information may seem obvious, this is an even more decisive aspect when rapid answers are needed for ENPs. Here we rank the available tools/methods, highlight main study gaps and list priority needs and the way forward. PMID- 26549754 TI - Reliability of stable Pb isotopes to identify Pb sources and verifying biological fractionation of Pb isotopes in goats and chickens. AB - Stable Pb isotope ratios (Pb-IRs) have been recognized as an efficient tool for identifying sources. This study carried out at Kabwe mining area, Zambia, to elucidate the presence or absence of Pb isotope fractionation in goat and chicken, to evaluate the reliability of identifying Pb pollution sources via analysis of Pb-IRs, and to assess whether a threshold for blood Pb levels (Pb-B) for biological fractionation was present. The variation of Pb-IRs in goat decreased with an increase in Pb-B and were fixed at certain values close to those of the dominant source of Pb exposure at Pb-B > 5 MUg/dL. However, chickens did not show a clear relationship for Pb-IRs against Pb-B, or a fractionation threshold. Given these, the biological fractionation of Pb isotopes should not occur in chickens but in goats, and the threshold for triggering biological fractionation is at around 5 MUg/dL of Pb-B in goats. PMID- 26549755 TI - Development of sintering-resistant CaO-based sorbent derived from eggshells and bauxite tailings for cyclic CO2 capture. AB - Carbon dioxide, one of the major greenhouse gases, are believed to be a major contributor to global warming. As a consequence, it is imperative for us to control and remove CO2 emissions. The CaO, a kind of effective CO2 sorbent at high temperature, has attracted increasing attention due to some potential advantages. The main drawback in practical application is the deterioration of CO2 capture capacity following multiples cycles. In the present study, novel low cost porous CaO-based sorbents with excellent CO2 absorption-desorption performance were synthesized using bauxite tailings (BTs) and eggshells as raw materials via solid-phase method. Effect of different BTs content on CO2 absorption-desorption properties was investigated. Phase composition and morphologies were analyzed by XRD and SEM, and CO2 absorption properties were investigated by the simultaneous thermogravimetric analyzer. The as-prepared CaO based sorbent doped with 10 wt% BTs showed superior CO2 absorption stability during multiple absorption-desorption cycles, with being >55% conversion after 40 cycles. This improved CO2 absorption performance was attributed to the particular morphologies of the CaO-based sorbents. Additionally, during absorption desorption cycles the occurrence of Ca12Al14O33 phase is considered to be responsible for the excellent CO2 absorption performance of CaO-based sorbents. In the meanwhile, the use of solid waste eggshell and BTs not only decreases the release of solid waste, but also moderates the greenhouse effect resulted from CO2. PMID- 26549757 TI - Platelet - derived CD154 antigen in patients with chronic kidney disease. AB - INTRODUCTION: CD154 is a surface glycoprotein present on activated platelets, lymphocytes and mast cells. It mediates the transmission of information between cells and initiates an inflammatory response. The interaction of CD154 with its receptor CD40 leads to increase in concentrations of soluble forms of both molecules (sCD154, sCD40), which has an important prognostic value in cardiovascular complications. The metabolic disorders in chronic kidney disease (CKD), chronic inflammation, increased oxidative stress and type of renal replacement therapy may influence on the balance of sCD154/sCD40 in plasma and blood platelets. The purpose of the reasearch was to analyse the concentrations of sCD154 antigen and sCD40 receptor in platelet pure plasma (PPP) and platelet rich plasma (PRP) of patients with CKD treated conservatively, haemodialysed and on petitoneal dialysis. METHODS: The group examined comprised 141 patients with chronic kidney disease: in pre-dialysis stage (n = 68), haemodialysed (n = 38) and on peritoneal dialysis (n = 35). The concentrations of sCD154 and sCD40 in PRP and PPP were determined with an ELISA method. The biochemical parameters were obtained using colorimetric method. RESULTS: The concentrations of sCD154 and sCD40 in PPP and PRP in examined group were significantly different depending on the method of renal replacement therapy. The haemodialysis procedure caused a significant increase in sCD40 concentration in PRP. The concentrations of sCD40 and sCD154 were correlated with lipid parameters. CONCLUSIONS: The type of renal replacement therapy influences on platelet activation which may be a factor contributing to increased cardiovascular complications in patients suffering from CKD. PMID- 26549756 TI - Chemostat culture systems support diverse bacteriophage communities from human feces. AB - BACKGROUND: Most human microbiota studies focus on bacteria inhabiting body surfaces, but these surfaces also are home to large populations of viruses. Many are bacteriophages, and their role in driving bacterial diversity is difficult to decipher without the use of in vitro ecosystems that can reproduce human microbial communities. RESULTS: We used chemostat culture systems known to harbor diverse fecal bacteria to decipher whether these cultures also are home to phage communities. We found that there are vast viral communities inhabiting these ecosystems, with estimated concentrations similar to those found in human feces. The viral communities are composed entirely of bacteriophages and likely contain both temperate and lytic phages based on their similarities to other known phages. We examined the cultured phage communities at five separate time points over 24 days and found that they were highly individual-specific, suggesting that much of the subject-specificity found in human viromes also is captured by this culture-based system. A high proportion of the community membership is conserved over time, but the cultured communities maintain more similarity with other intra subject cultures than they do to human feces. In four of the five subjects, estimated viral diversity between fecal and cultured communities was highly similar. CONCLUSIONS: Because the diversity of phages in these cultured fecal communities have similarities to those found in humans, we believe these communities can serve as valuable ecosystems to help uncover the role of phages in human microbial communities. PMID- 26549758 TI - Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2. AB - T-cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related genes and the activation of lymphocyte-specific programmes. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor forms a complex with Polycomb repressive complex 2 (PRC2) in CD4(-)CD8(-) thymocytes and allows its binding to more than 500 developmentally regulated loci, including those normally activated in haematopoietic stem cells and others induced by the Notch pathway. Loss of Ikaros in CD4(-)CD8(-) cells leads to reduced histone H3 lysine 27 trimethylation and ectopic gene expression. Furthermore, Ikaros binding triggers PRC2 recruitment and Ikaros interacts with PRC2 independently of the nucleosome remodelling and deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells. PMID- 26549760 TI - Drug release from ordered mesoporous silicas. AB - The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation. PMID- 26549759 TI - Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli. AB - During urinary tract infection (UTI), the second most common bacterial infection, dynamic interactions take place between uropathogenic E. coli (UPEC) and host urothelial cells. While significant strides have been made in the identification of the virulence factors of UPEC, our understanding of how the urothelial cells mobilize innate defenses against the invading UPEC remains rudimentary. Here we show that mouse urothelium responds to the adhesion of type 1-fimbriated UPEC by rapidly activating the canonical NF-kappaB selectively in terminally differentiated, superficial (umbrella) cells. This activation depends on a dual ligand/receptor system, one between FimH adhesin and uroplakin Ia and another between lipopolysaccharide and Toll-like receptor 4. When activated, all the nuclei (up to 11) of a multinucleated umbrella cell are affected, leading to significant amplification of proinflammatory signals. Intermediate and basal cells of the urothelium undergo NF-kappaB activation only if the umbrella cells are detached or if the UPEC persistently express type 1-fimbriae. Inhibition of NF-kappaB prevents the urothelium from clearing the intracellular bacterial communities, leading to prolonged bladder colonization by UPEC. Based on these data, we propose a model of dual ligand/receptor system in innate urothelial defenses against UPEC. PMID- 26549761 TI - Transient transfection of macrophage migration inhibitory factor small interfering RNA disrupts the biological behavior of oral squamous carcinoma cells. AB - Macrophage migration inhibitory factor (MIF) is closely associated with tumorigenesis. The present study aimed to investigate the effects of MIF on the proliferation, migration and colony formation of oral squamous cell carcinoma (OSCC), and to quantify the protein expression levels of MIF in OSCC tissue samples. Firstly, small interfering (si)RNA was used to knock down the gene expression of MIF in Tca8113, HN5 and SCC25 OSCC cells. Secondly, proliferation, migration and colony formation of the OSCC cells were determined by MTT, transmigration and colony formation assays, respectively. Western blotting was performed to detect changes in the protein expression levels of the epithelial mesenchymal transition markers, Twist-related protein 1 (Twist1), matrix metalloproteinase (MMP)-2 and MMP-9. Finally, immunohistochemistry was used to examine the protein expression of MIF in OSCC tissue samples. The results demonstrated that siRNA against MIF significantly downregulated the expression levels of MIF in all OSCC cells, and decreased their proliferation and migration ability. Colony formation ability was also inhibited in the OSCC cells following transfection with MIF siRNA. Furthermore, western blotting demonstrated that the protein expression of Twist1 was decreased similarly to those of MIF. The protein expression of MMP-2 revealed no change, whereas that of MMP-9 decreased. The protein expression of MIF was detected in OSCC tissue samples with staining predominantly located in the cell membrane and cytoplasm. The present study demonstrated that MIF may be important in the pathogenesis and progression of OSCC, and indicated its potential therapeutic value. PMID- 26549762 TI - Mechanical cytoprotection: A review of cytoskeleton-protection approaches for cells. AB - We review a class of cutting-edge approaches for cytoprotection of cells exposed to assaults such as sustained deformations, chemotherapy, radiotherapy, or ischemia. These approaches will enhance cell survival by mechanically protecting the structure and dynamics of the actin cytoskeleton (CSK). Cortical actin provides structural support to the plasma membrane (PM), protecting its integrity. Consequently, assaults can fragment the actin cortex leading to local, mechanical failure of the PM and poration of the cell. This disrupts normal trafficking of biomolecules across the PM, leading to loss of homeostasis and eventually, to cell death and tissue necrosis. Two different approaches to cytoskeletal protection are covered in this review paper. The first is to supply energy-related molecules to maintain and enhance the energy-consuming dynamics of the actin CSK. The second is to stabilize newly formed actin CSK directly for example through cross-linking or reinforcement at PM anchoring sites. Research in this area is clearly still in its infancy. Very few studies have gone beyond characterizing the effects of induced damage to the actin CSK (and subsequent PM collapse). Recent work, focusing instead on sustaining the actin under non physiological or pathophysiological conditions, has shown great promise. Such cytoskeletal-protection may find medical applications in preventing or minimizing tissue damage when tissues are unhealthy or at risk, or in enhancing cell performance under stress. Here, we condense the relevant cell biology and biomechanics background, assess candidate cytoskeletal protective agents, and review published works that have shown potential for medical benefit in experimental model systems. PMID- 26549763 TI - A point-wise normalization method for development of biofidelity response corridors. AB - An updated technique to develop biofidelity response corridors (BRCs) is presented. BRCs provide a representative range of time-dependent responses from multiple experimental tests of a parameter from multiple biological surrogates (often cadaveric). The study describes an approach for BRC development based on previous research, but that includes two key modifications for application to impact and accelerative loading. First, signal alignment conducted prior to calculation of the BRC considers only the loading portion of the signal, as opposed to the full time history. Second, a point-wise normalization (PWN) technique is introduced to calculate correlation coefficients between signals. The PWN equally weighs all time points within the loading portion of the signals and as such, bypasses aspects of the response that are not controlled by the experimentalist such as internal dynamics of the specimen, and interaction with surrounding structures. An application of the method is presented using previously-published thoracic loading data from 8 lateral sled PMHS tests conducted at 8.9m/s. Using this method, the mean signals showed a peak lateral load of 8.48kN and peak chest acceleration of 86.0g which were similar to previously-published research (8.93kN and 100.0g respectively). The peaks occurred at similar times in the current and previous studies, but were delayed an average of 2.1ms in the updated method. The mean time shifts calculated with the method ranged from 7.5% to 9.5% of the event. The method may be of use in traditional injury biomechanics studies and emerging work on non-horizontal accelerative loading. PMID- 26549764 TI - Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc. AB - The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12-20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration. PMID- 26549765 TI - Zone-specific integrated cartilage repair using a scaffold-free tissue engineered construct derived from allogenic synovial mesenchymal stem cells: Biomechanical and histological assessments. AB - The purpose of the present study was to investigate the zone-specific integration properties of articular cartilage defects treated in vivo with scaffold-free three-dimensional tissue-engineered constructs (TECs) derived from allogenic synovial mesenchymal stem cells (MSCs) in a porcine model. The TEC derived from the synovial MSCs was implanted into chondral defects in the medial femoral condyle of the knee. The integration boundary of repair tissue with the adjacent host cartilage was morphologically and biomechanically evaluated at 6 months post implantation. Histological assessments showed that the repair tissue in each zone was well integrated with the adjacent host cartilage, with an apparent secure continuity of the extracellular matrix. There were no significant differences in histological scores between the integration boundary and the center of the repair tissue at every zone. Nonetheless, in all the specimens subjected to mechanical testing, failure occurred at the integration boundary. The average tensile strength of the integration boundary vs normal cartilage was 0.6 vs 4.9, 3.0 vs 12.6, and 5.5 vs 12.8MPa at the superficial, middle, and deep layers, respectively. Thus, these results indicate the most fragile point in the repair tissue remained at the integration boundary in spite of the apparent secure tissue continuity and equivalent histological quality with the center of the repair tissue. Such tissue vulnerability at the surface integration boundary could affect the long-term durability of the tissue repair, and thus, special consideration will be needed in the post-operative rehabilitation programming to enhance the longevity of such repair tissues in response to normal knee loading. PMID- 26549766 TI - Fluid-flow dependent response of intervertebral discs under cyclic loading: On the role of specimen preparation and preconditioning. AB - In vivo during the day, intervertebral discs are loaded mainly in compression causing fluid and height losses that are subsequently fully recovered overnight due to fluid inflow under smaller compression. However, in vitro, fluid flow through the endplates, in particular fluid imbibition, is hampered possibly by blood clots formed post mortem. Despite earlier in vitro studies, it remains yet unclear if and how fluid flow conditions in vitro could properly emulate those in vivo. Effects of various preload magnitudes (no preload, 0.06 and 0.28 MPa) and disc-bone preparation conditions (e.g., w/o bony endplates) on disc height and nucleus pressure were investigated using 54 bovine specimens. Changes in specimen height and pressure at different nucleus locations were used as surrogate measures to assess the fluid content and flow within the discs. Under all investigated preparation conditions and preload magnitudes, no significant pressure recovery could be obtained during low loading phases, even without bony endplates. On the contrary, partial to full displacement recovery were reached in particular under 0.28 MPa preload. Results highlight the significant role of disc preload magnitude in disc height recovery during low loading periods. Attention should hence be given in future studies to the proper selection of preload magnitude and duration as well as the animal models used if in vivo response is intended to be replicated. Findings also indicate that flushing the endplates or injection of bone cement respectively neither facilitates nor impedes fluid flow into or out of the disc to a noticeable degree in this bovine disc model. PMID- 26549767 TI - High-sensitivity elemental ionization for quantitative detection of halogenated compounds. AB - The rising importance of organohalogens in environmental, pharmaceutical, and biological applications has drawn attention to analysis of these compounds in recent years. Elemental mass spectrometry (MS) is particularly advantageous in this regard because of its ability to quantify without compound-specific standards. However, low sensitivity of conventional elemental MS for halogens has hampered applications of this powerful method in organohalogen analyses. To this end, we have developed a high-sensitivity elemental ion source compatible with widely available atmospheric-sampling mass spectrometers. We utilize a helium oxygen plasma for atomization followed by negative ion formation in plasma afterglow, a configuration termed as plasma-assisted reaction chemical ionization (PARCI). The effect of oxygen on in-plasma and afterglow reactions is investigated, leading to fundamental understanding of ion generation processes as well as optimized operating conditions. Coupled to a gas chromatograph, PARCI shows constant ionization efficiency for F, Cl, and Br regardless of the chemical structure of the compounds. Negative ionization in the afterglow improves halide ion formation efficiency and eliminates isobaric interferences, offering sub picogram elemental detection for F, Cl, and Br using low-resolution MS. Notably, the detection limit for F is about one order of magnitude better than other elemental MS techniques. The high sensitivity and facile adoptability of PARCI pave the way for combined elemental-molecular characterization, a comprehensive analytical scheme for rapid identification and quantification of organohalogens. PMID- 26549768 TI - Effect of group size and maize silage dietary levels on behaviour, health, carcass and meat quality of Mediterranean buffaloes. AB - The effects of different dietary levels of maize silage (10% v. 36% DM) and group size (7 v. 14 animals) were assessed on growth performance and in vivo digestibility of 28 male fattening buffaloes. In addition, the effects of diet on meat quality and group size on behaviour and immune response were separately evaluated. Animals were weighed and assigned to three groups. The high silage - low size group (HL) was fed a total mixed ration (TMR) containing 36% DM of maize silage and consisted of seven animals (age 12.7+/-2.6 months; BW 382.2+/-67.7 kg at the start of the study). The low silage - low size group (LL) was fed a TMR containing 10% DM of maize silage and consisted of seven animals (age 13.0+/-2.7 months; BW 389.4+/-72.3 kg). The high silage - high size group (HH) was fed the 36% maize silage DM diet and consisted of 14 animals (age 13.9+/-3.25 months; BW 416.5+/-73.9 kg). Total space allowance (3.2 indoor+3.2 outdoor m2/animal) was kept constant in the three groups, as well as the ratio of animals to drinkers (seven animals per water bowl) and the manger space (70 cm per animal). Growth performance, carcass characteristics and digestibility were influenced neither by dietary treatment nor by group size, even if the group fed 36% maize silage diet showed a higher fibre digestibility. No effect of diet was found on meat quality. Group size did not affect the behavioural activities with the exception of drinking (1.04+/-0.35% v. 2.60+/-0.35%; P<0.01 for groups HL and HH, respectively) and vigilance (2.58+/-0.46% v. 1.20+/-0.46%; P<0.05 for groups HL and HH, respectively). Immune responses were not affected by group size. PMID- 26549769 TI - Child protection workers dealing with child abuse: The contribution of personal, social and organizational resources to secondary traumatization. AB - The present study compared secondary traumatization among child protection social workers versus social workers employed at social service departments. In addition, based on Conservation of Resources (COR) theory, the study examined the contribution of working in the field of child protection as well as the contribution of background variables, personal resources (mastery), and resources in the workers' social and organizational environment (social support, effectiveness of supervision, and role stress) to secondary traumatization. The findings indicate that levels of mastery and years of work experience contributed negatively to secondary traumatization, whereas exposure to child maltreatment, trauma history, and role stress contributed positively to secondary traumatization. However, no significant contribution was found for social support and effectiveness of supervision. The study identifies factors that can prevent distress among professionals such as child protection workers, who are exposed to the trauma of child abuse victims. Recommendations are provided accordingly. PMID- 26549770 TI - Health Care for Adolescents in Taiwan: An Emerging Role of Pediatricians. PMID- 26549771 TI - Commercialisation of Biomarker Tests for Mental Illnesses: Advances and Obstacles. AB - Substantial strides have been made in the field of biomarker research for mental illnesses over the past few decades. However, no US FDA-cleared blood-based biomarker tests have been translated into routine clinical practice. Here, we review the challenges associated with commercialisation of research findings and discuss how these challenges can impede scientific impact and progress. Overall evidence indicates that a lack of research funding and poor reproducibility of findings were the most important obstacles to commercialization of biomarker tests. Fraud, pre-analytical and analytical limitations, and inappropriate statistical analysis are major contributors to poor reproducibility. Increasingly, these issues are acknowledged and actions are being taken to improve data validity, raising the hope that robust biomarker tests will become available in the foreseeable future. PMID- 26549772 TI - Hair Coloration by Gene Regulation: Fact or Fiction? AB - The unravelling of hair pigmentation genetics and robust delivery systems to the hair follicle (HF) will allow the development of a new class of colouring products. The challenge will be changing hair colour from inside out by safely regulating the activity of target genes through the specific delivery of synthetic/natural compounds, proteins, genes, or small RNAs. PMID- 26549773 TI - Pretreatment of biomass. PMID- 26549774 TI - Proximate causes of the variation of the human sex ratio at birth. AB - There is evidence that the human sex ratio (proportion males at birth) is the result of two processes. First, the sexes of zygotes (from which the primary sex ratio would be calculated) are thought to be partially controlled by the hormone levels of both parents around the time of conception. Second, this primary sex ratio is apparently modified downwards by male-sex-selective spontaneous abortion caused by high levels of maternal stress-induced adrenal androgens, thus yielding the sex ratio at birth (the secondary sex ratio). Since maternal stress is one cause of spontaneous abortion (and of other forms of reproductive sub optimality), and since some forms of pharmacological treatment of maternal stress are deleterious to the foetus, best practice would suggest non-pharmacological treatment (e.g. psychotherapy, hypnosis or massage) for pregnant women who have a previous history of spontaneous abortion, preterm birth or low-birth-weight infants. PMID- 26549775 TI - Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses. AB - Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile, Fusobacterium varium, Haemophilus parainfluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development. PMID- 26549776 TI - Perception et receptivite des proches-aidants a l'egard de la videosurveillance intelligente pour la detection des chutes des aines a domicile. AB - To address the issue of falls, which are increasing as the population ages, an intelligent video-monitoring system is being developed. The aim of the study is to explore caregivers' perceptions of and receptiveness to a prototype of this fall detection system. A cross-sectional mixed-method study was carried out with individual interviews of 18 caregivers. Statistical frequencies and content analysis were conducted (SPSS and N'Vivo). The results show that most participants (n = 15/18) liked the intelligent video-monitoring system and were willing to use it. They would worry less if they could be alerted if a care recipient fell, but they were concerned about privacy and cost. Participants had a positive perception of the system and expressed their wishes regarding the kind of alert and the person to contact in case of a fall. PMID- 26549777 TI - RADBIOMOD: A simple program for utilising biological modelling in radiotherapy plan evaluation. AB - PURPOSE: Radiotherapy plan evaluation is currently performed by assessing physical parameters, which has many limitations. Biological modelling can potentially allow plan evaluation that is more reflective of clinical outcomes, however further research is required into this field before it can be used clinically. METHODS: A simple program, RADBIOMOD, has been developed using Visual Basic for Applications (VBA) for Microsoft Excel that incorporates multiple different biological models for radiotherapy plan evaluation, including modified Poisson tumour control probability (TCP), modified Zaider-Minerbo TCP, Lyman Kutcher-Burman normal tissue complication probability (NTCP), equivalent uniform dose (EUD), EUD-based TCP, EUD-based NTCP, and uncomplicated tumour control probability (UTCP). RADBIOMOD was compared to existing biological modelling calculators for 15 sample cases. RESULTS: Comparing RADBIOMOD to the existing biological modelling calculators, all models tested had mean absolute errors and root mean square errors less than 1%. CONCLUSIONS: RADBIOMOD produces results that are non-significantly different from existing biological modelling calculators for the models tested. It is hoped that this freely available, user friendly program will aid future research into biological modelling. PMID- 26549778 TI - A prospective evaluation of the anterior horn of the lateral meniscus as a landmark for tibial tunnel placement in anterior cruciate ligament (ACL) reconstruction. AB - BACKGROUND: The goal of this study was to prospectively evaluate the accuracy and consistency of the anterior horn of the lateral meniscus as a landmark in achieving the desired tibial tunnel location during primary anterior cruciate ligament (ACL) reconstruction. METHODS: One hundred consecutive adult patients undergoing primary ACL reconstruction were enrolled in the study. One sports fellowship trained surgeon performed all ACL reconstructions using independent tunnel drilling with an accessory anteromedial portal for the femoral tunnel. All guide pins for the tibial tunnel were placed using a 55-degree guide using the posterior border of the anterior horn of the lateral meniscus as a landmark. Following pin placement, a true lateral fluoroscopic image was obtained. These were digitally analyzed to measure the location of the pin along the length of the tibial plateau. RESULTS: The average anteroposterior (A-P) distance achieved using the posterior border of the anterior horn of the lateral meniscus as a landmark for tibial tunnel placement was 37.0%+/-5.2% (mean+/-standard deviation) [range 26.4%-49.2%]. 66% of tibial tunnels were located between 30.0% and 39.9% of the A-P tibial distance. Only 18% of tibial tunnels localized between 40.0% and 44.9%, the area of the anatomic footprint described by Staubli and Rauschning [9] 16% of patients were significant outliers, with tunnels localizing to 25.0% 29.9% (6 patients) or 45.0%-49.9% (10 patients). CONCLUSIONS: Use of the posterior border of the anterior horn of the lateral meniscus as a landmark for tibial tunnel placement during anatomic ACL reconstruction yields an inconsistent tunnel location. LEVEL OF EVIDENCE: II, Prospective study. PMID- 26549779 TI - Differences in developmental strategies between long-settled and invasion-front populations of the cane toad in Australia. AB - Phenotypic plasticity can enhance a species' ability to persist in a new and stressful environment, so that reaction norms are expected to evolve as organisms encounter novel environments. Biological invasions provide a robust system to investigate such changes. We measured the rates of early growth and development in tadpoles of invasive cane toads (Rhinella marina) in Australia, from a range of locations and at different larval densities. Populations in long-colonized areas have had the opportunity to adapt to local conditions, whereas at the expanding range edge, the invader is likely to encounter challenges that are both novel and unpredictable. We thus expected invasion-vanguard populations to exhibit less phenotypic plasticity than range-core populations. Compared to clutches from long-colonized areas, clutches from the invasion front were indeed less plastic (i.e. rates of larval growth and development were less sensitive to density). In contrast, those rates were highly variable in clutches from the invasion front, even among siblings from the same clutch under standard conditions. Clutches with highly variable rates of growth and development under constant conditions had lower phenotypic plasticity, suggesting a trade-off between these two strategies. Although these results reveal a strong pattern, further investigation is needed to determine whether these different developmental strategies are adaptive (i.e. adaptive phenotypic plasticity vs. bet-hedging) or instead are driven by geographic variation in genetic quality or parental effects. PMID- 26549780 TI - Comorbidities of epilepsy: current concepts and future perspectives. AB - The burden of comorbidity in people with epilepsy is high. Several diseases, including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Several mechanisms explain how epilepsy and comorbidities are associated, including shared risk factors and bidirectional relations. There is a pressing need for new and validated screening instruments and guidelines to help with the early detection and treatment of comorbid conditions. Preliminary evidence suggests that some conditions, such as depression and migraine, negatively affect seizure outcome and quality of life. Further investigation is needed to explore these relations and the effects of targeted interventions. Future advances in the investigation of the comorbidities of epilepsy will strengthen our understanding of epilepsy and could play an important part in stratification for genetic studies. PMID- 26549781 TI - MRI quantifies neuromuscular disease progression. PMID- 26549782 TI - MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. AB - BACKGROUND: A substantial impediment to progress in trials of new therapies in neuromuscular disorders is the absence of responsive outcome measures that correlate with patient functional deficits and are sensitive to early disease processes. Irrespective of the primary molecular defect, neuromuscular disorder pathological processes include disturbance of intramuscular water distribution followed by intramuscular fat accumulation, both quantifiable by MRI. In pathologically distinct neuromuscular disorders, we aimed to determine the comparative responsiveness of MRI outcome measures over 1 year, the validity of MRI outcome measures by cross-sectional correlation against functionally relevant clinical measures, and the sensitivity of specific MRI indices to early muscle water changes before intramuscular fat accumulation beyond the healthy control range. METHODS: We did a prospective observational cohort study of patients with either Charcot-Marie-Tooth disease 1A or inclusion body myositis who were attending the inherited neuropathy or muscle clinics at the Medical Research Council (MRC) Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK. Genetic confirmation of the chromosome 17p11.2 duplication was required for Charcot-Marie-Tooth disease 1A, and classification as pathologically or clinically definite by MRC criteria was required for inclusion body myositis. Exclusion criteria were concomitant diseases and safety related MRI contraindications. Healthy age-matched and sex-matched controls were also recruited. Assessments were done at baseline and 1 year. The MRI outcomes fat fraction, transverse relaxation time (T2), and magnetisation transfer ratio (MTR)-were analysed during the 12-month follow-up, by measuring correlation with functionally relevant clinical measures, and for T2 and MTR, sensitivity in muscles with fat fraction less than the 95th percentile of the control group. FINDINGS: Between Jan 19, 2010, and July 7, 2011, we recruited 20 patients with Charcot-Marie-Tooth disease 1A, 20 patients with inclusion body myositis, and 29 healthy controls (allocated to one or both of the 20-participant matched-control subgroups). Whole muscle fat fraction increased significantly during the 12-month follow-up at calf level (mean absolute change 1.2%, 95% CI 0.5-1.9, p=0.002) but not thigh level (0.2%, -0.2 to 0.6, p=0.38) in patients with Charcot-Marie-Tooth disease 1A, and at calf level (2.6%, 1.3-4.0, p=0.002) and thigh level (3.3%, 1.8 4.9, p=0.0007) in patients with inclusion body myositis. Fat fraction correlated with the lower limb components of the inclusion body myositis functional rating score (rho=-0.64, p=0.002) and the Charcot-Marie-Tooth examination score (rho=0.63, p=0.003). Longitudinal T2 and MTR changed consistently with fat fraction but more variably. In muscles with a fat fraction lower than the control group 95th percentile, T2 was increased in patients compared with controls (regression coefficients: inclusion body myositis thigh 4.0 ms [SE 0.5], calf 3.5 ms [0.6]; Charcot-Marie-Tooth 1A thigh 1.0 ms [0.3], calf 2.0 ms [0.3]) and MTR reduced compared with controls (inclusion body myositis thigh -1.5 percentage units [pu; 0.2], calf -1.1 pu [0.2]; Charcot-Marie-Tooth 1A thigh -0.3 pu [0.1], calf -0.7 pu [0.1]). INTERPRETATION: MRI outcome measures can monitor intramuscular fat accumulation with high responsiveness, show validity by correlation with conventional functional measures, and detect muscle water changes preceding marked intramuscular fat accumulation. Confirmation of our results in further cohorts with these and other muscle-wasting disorders would suggest that MRI biomarkers might prove valuable in experimental trials. FUNDING: Medical Research Council UK. PMID- 26549784 TI - Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells. AB - Many viruses have evolved strategies of so-called "superinfection exclusion" to prevent re-infection of a cell that the same virus has already infected. Although Old World arenavirus infection results in down-regulation of its viral receptor and thus superinfection exclusion, whether New World arenaviruses have evolved such a mechanism remains unclear. Here we show that acute infection by the New World Junin virus (JUNV) failed to down-regulate the transferrin receptor and did not induce superinfection exclusion. We observed that Vero cells infected by a first round of JUNV (Candid1 strain) preserve an ability to internalize new incoming JUNV particles that is comparable to that of non-infected cells. Moreover, we developed a dual infection assay with the wild-type Candid1 JUNV and a recombinant JUNV-GFP virus to discriminate between first and second infections at the transcriptional and translational levels. We found that Vero and A549 cells already infected by JUNV were fully competent to transcribe viral RNA from a second round of infection. Furthermore, flow cytometry analysis of viral protein expression indicated that viral translation was normal, regardless of whether cells were previously infected or not. We conclude that in acutely infected cells, Junin virus lacks a superinfection exclusion mechanism. PMID- 26549785 TI - Faster reduction in hyperinflation and improvement in lung ventilation inhomogeneity promoted by aclidinium compared to glycopyrronium in severe stable COPD patients. A randomized crossover study. AB - Standard spyrometric assessment in chronic obstructive pulmonary disease (COPD) only evaluates bronchial obstruction. However, airflow limitation and hyperinflation are the main pathophysiological factors responsible for dyspnoea and reduced exercise tolerance in patients with COPD. This study evaluated the effects of aclidinium bromide 400 MUg and glycopyrronium bromide 50 MUg on these parameters. Patients with stable severe/very severe COPD were randomized in this double-blind, double-dummy, crossover, Phase IV study. Patients received single doses of each drug on separate days. Primary endpoints were changes in residual volume (RV) and intra-thoracic gas volume (ITGV), assessed by full-body plethysmography. Other endpoints included changes variations in lung ventilation inhomogeneity (Phase III slope of single-breath nitrogen washout test, SBN2), dyspnoea visual analogue scale, and pulmonary specific total airway resistances. Assessments were performed at baseline and 5, 15, 30, 60, and 180 min post administration. Thirty-seven patients were randomized (31 male; mean age 71 years). Aclidinium and glycopyrronium significantly improved ITGV versus baseline at all-time points (p < 0.05). Significant improvements in RV were observed after 5 min with aclidinium and after 60 min with glycopyrronium. RV improvements were significantly greater with aclidinium than glycopyrronium from 5 to 60 min post administration (p < 0.05). Both treatments improved dyspnoea versus baseline at all-time points (p < 0.05). Aclidinium significantly improved ventilation inhomogeneity versus baseline at all-time points; no significant changes were observed for glycopyrronium. For the first time two long-acting muscarinic antagonists have been compared in acute conditions with body plethysmography and SBN2 test. We demonstrated that both aclidinium and glycopyrronium significantly reduce hyperinflation and dyspnoea in severe and very severe COPD patients. Aclidinium however promoted a faster reduction in RV and was the only able to reduce lung ventilation inhomogeneity. Trial Registration numbers available on Clinicaltrials.gov: NCT02181023. PMID- 26549787 TI - Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease. AB - Alzheimer's disease (AD) is a neurodegenerative disease affecting over 20 million people worldwide, mainly adult subjects in advanced age. Over 240 different fully penetrant autosomal dominant mutations in 532 families around the world have been described in three genes [i.e., amyloid precursor protein (APP), and presenilins (PSEN1 and PSEN2)] causing 50% of all Familial AD. We report a new mutation (p.Ile408Thr, c. 1223T>C) in the PSEN1 gene in one autosomal dominant Late Onset AD patient. The genetic variation occurred in a conserved domain of the protein and was present in the proband and in the younger sister who is likely to be prodromal AD. Thus, we suggest that this variant will have probably a pathogenic effect, hypothesizing a possible key role of this new mutation in the pathogenesis of Alzheimer's disease for this family. PMID- 26549786 TI - Role of the dorsal medulla in the neurogenesis of airway protection. AB - The dorsal medulla encompassing the nucleus of the tractus solitarius (NTS) and surrounding reticular formation (RF) has an important role in processing sensory information from the upper and lower airways for the generation and control of airway protective behaviors. These behaviors, such as cough and swallow, historically have been studied in isolation. However, recent information indicates that these and other airway protective behaviors are coordinated to minimize risk of aspiration. The dorsal medullary neural circuits that include the NTS are responsible for rhythmogenesis for repetitive swallowing, but previous models have assigned a role for this portion of the network for coughing that is restricted to monosynaptic sensory processing. We propose a more complex NTS/RF circuit that controls expression of swallowing and coughing and the coordination of these behaviors. The proposed circuit is supported by recordings of activity patterns of selected neural elements in vivo and simulations of a computational model of the brainstem circuit for breathing, coughing, and swallowing. This circuit includes separate rhythmic sub-circuits for all three behaviors. The revised NTS/RF circuit can account for the mode of action of antitussive drugs on the cough motor pattern, as well as the unique coordination of cough and swallow by a meta-behavioral control system for airway protection. PMID- 26549788 TI - Aging and the complexity of center of pressure in static and dynamic postural tasks. AB - The experiment was set-up to investigate the hypothesis that there is an age related bi-directional change in complexity of the center of pressure (COP) depending on postural task demands. Healthy young (19-28 year) and old (65-74 year) adults were instructed to match, in two 25s trials for each condition, the COP with constant and sine-wave targets at 2 levels (5 and 40%) of the maximal COP distance (MCD). The root mean square error of COP increased with aging in both MCD levels and tasks. Multi-scale entropy (MSE) and detrended fluctuation analysis showed that the complexity of COP in the old adults was lower compared to the young in the constant target, whereas it was higher in the sine-wave target. The task dependent age-related bi-directional change of COP complexity is counter to the hypothesis of a universal loss of complexity with aging but shows that there is loss of adaptive change in complexity driven by the COP dynamics. PMID- 26549789 TI - Dual-energy computed tomography for detection of coronary artery disease. AB - Recent technological advances in computed tomography (CT) technology have fulfilled the prerequisites for the cardiac application of dual-energy CT (DECT) imaging. By exploiting the unique characteristics of materials when exposed to two different x-ray energies, DECT holds great promise for the diagnosis and management of coronary artery disease. It allows for the assessment of myocardial perfusion to discern the hemodynamic significance of coronary disease and possesses high accuracy for the detection and characterization of coronary plaques, while facilitating reductions in radiation dose. As such, DECT enabled cardiac CT to advance beyond the mere detection of coronary stenosis expanding its role in the evaluation and management of coronary atherosclerosis. PMID- 26549790 TI - Prediction of amino acid positions specific for functional groups in a protein family based on local sequence similarity. AB - The exchange of single amino acid residue in protein can substantially affect the specificity of molecular recognition. Many protein families can be divided into the groups based on specificity to recognized ligands. Prediction of group discriminating residues within the certain family is extremely necessary for theoretical studies, enzyme engineering, drug design, and so on. The most existing methods use the multiple sequence alignment. They have the limitations in prediction accuracy due to the family sequence divergence and ligand-based grouping. We developed a new method SPrOS (Specificity Projection On Sequence) for estimating the specificity of residues to user-defined groups. SPrOS compares the sequence segments from the test protein and training proteins. Contrary to other segment-comparison approaches extracting the string motifs, SPrOS calculates the scores for single positions by the similarity of their surroundings. The method was evaluated on the simulated sequences and real protein families. The high-prediction accuracy was achieved for simulated sequences, in which SPrOS detected specific positions not predicted with the alignment-based method. For bacterial transcription factors (LacI/GalR) clearly divided into functional groups, the predicted specific residues corresponded to the published experimental data. In a more complicated case of protein kinases classified by inhibitor specificity, the positions predicted with high significance were located in ligand-binding areas. As the ligand specificity is not necessary coincided with phylogeny, evolutionary-coupled mutations could disturb the detection of ligand-specific residues. Excluding proximate homologs of the test protein kinase from the training set, we improved the prediction of the ligand-specific residues. The SPrOS is available at http://www.way2drug.com/spros/ PMID- 26549791 TI - Evaluating Shortened Versions of the AUDIT as Screeners for Alcohol Use Problems in a General Population Study. AB - BACKGROUND: Efficient alcohol screening measures are important to prevent or treat alcohol use disorders (AUDs). OBJECTIVES: We studied different versions of the Alcohol Use Disorders Identification Test (AUDIT) comparing their performance to the full AUDIT and an AUD measure as screeners for alcohol use problems in Goa, India. METHODS: Data from a general population study on 743 male drinkers aged 18-49 years are reported. Drinkers completed the AUDIT and an AUD measure. We created shorter versions of the AUDIT by (a) collapsing AUDIT item responses into three and two categories and (b) deleting two items with the lowest factor loadings. Each version was evaluated using factor, reliability and validity, and differential item functioning (DIF) analysis by age, education, standard of living index (SLI), and area of residence. RESULTS: A single factor solution was found for each version with lower factor loadings for items on guilt and concern. There were no significant differences among the different AUDIT versions in predicting AUD. No significant DIF was found by education, SLI or area of residence. DIF was observed for the alcohol frequency item by age. CONCLUSIONS/IMPORTANCE: The AUDIT may be used with dichotomized response options without loss of predictive validity. A shortened eight-item dichotomized scale can adequately screen for AUDs in Goa when brevity is of paramount importance, although with lower predictive validity. Although the frequency item was endorsed more by older men, there is no evidence that the AUDIT items perform differently in other groups of male drinkers in Goa. PMID- 26549792 TI - Assessment of DNA double-strand breaks induced by intravascular iodinated contrast media following in vitro irradiation and in vivo, during paediatric cardiac catheterization. AB - Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X-ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess gammaH2AX-foci induction, which corresponded to the number of DNA double-strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double strand breaks beyond that induced by radiation for >= 17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double-strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X-ray radiation investigations. PMID- 26549793 TI - Anhydrous Amorphous Calcium Oxalate Nanoparticles from Ionic Liquids: Stable Crystallization Intermediates in the Formation of Whewellite. AB - The mechanisms by which amorphous intermediates transform into crystalline materials are not well understood. To test the viability and the limits of the classical crystallization, new model systems for crystallization are needed. With a view to elucidating the formation of an amorphous precursor and its subsequent crystallization, the crystallization of calcium oxalate, a biomineral widely occurring in plants, is investigated. Amorphous calcium oxalate (ACO) precipitated from an aqueous solution is described as a hydrated metastable phase, as often observed during low-temperature inorganic synthesis and biomineralization. In the presence of water, ACO rapidly transforms into hydrated whewellite (monohydrate, CaC2 O4 ?H2 O, COM). The problem of fast crystallization kinetics is circumvented by synthesizing anhydrous ACO from a pure ionic liquid (IL-ACO) for the first time. IL-ACO is stable in the absence of water at ambient temperature. It is obtained as well-defined, non-agglomerated particles with diameters of 15-20 nm. When exposed to water, it crystallizes to give (hydrated) COM through a dissolution/recrystallization mechanism. PMID- 26549795 TI - Prevalence of overweight/obesity and fitness level in preschool children from the north compared with the south of Europe: an exploration with two countries. AB - BACKGROUND: North-south differences in the prevalence of obesity and fitness levels have been found in European adolescents, yet it is unknown if such differences already exist in very young children. OBJECTIVES: This study aims to compare the prevalence of overweight/obesity and fitness levels in preschool children aged 4 years from Sweden (north of Europe) and Spain (south of Europe). METHODS: The sample consisted of 315 Swedish and 128 Spanish preschoolers. Anthropometry (weight, height, waist circumference) and fitness (strength, speed agility, balance and cardiorespiratory fitness) were assessed. Analysis of covariance adjusted for age, sex and height/body mass index (BMI) was used. RESULTS: Preschool children from Sweden had lower prevalence of overweight/obesity than their peers from Spain (World Obesity Federation, mean difference, MD = -9%, P = 0.010; World Health Organization, MD = -11%, P = 0.011). Concerning fitness, preschoolers from Spain were more fit in terms of upper-muscular strength (MD = +0.4 kg, P = 0.010), speed-agility (MD = -1.9 s, P = 0.001), balance (MD = +4.0 s, P = 0.001) and cardiorespiratory fitness (MD = boys = +6.6 laps, girls = +2.3 laps; P < 0.001 for all), yet they had worse lower muscular strength (MD = -7.1, P <= 0.001) than those from Sweden. Differences in upper-muscular strength were largely explained by differences in BMI, and differences in cardiorespiratory fitness should be interpreted cautiously due to some methodological deviations. CONCLUSIONS: These findings suggest that a higher prevalence of overweight/obesity in Spain compared with Sweden is present already at early childhood, while differences in physical fitness components showed mixed findings. PMID- 26549794 TI - Revisiting the reference genomes of human pathogenic Cryptosporidium species: reannotation of C. parvum Iowa and a new C. hominis reference. AB - Cryptosporidium parvum and C. hominis are the most relevant species of this genus for human health. Both cause a self-limiting diarrhea in immunocompetent individuals, but cause potentially life-threatening disease in the immunocompromised. Despite the importance of these pathogens, only one reference genome of each has been analyzed and published. These two reference genomes were sequenced using automated capillary sequencing; as of yet, no next generation sequencing technology has been applied to improve their assemblies and annotations. For C. hominis, the main challenge that prevents a larger number of genomes to be sequenced is its resistance to axenic culture. In the present study, we employed next generation technology to analyse the genomic DNA and RNA to generate a new reference genome sequence of a C. hominis strain isolated directly from human stool and a new genome annotation of the C. parvum Iowa reference genome. PMID- 26549796 TI - Profile of Institutional Ethics Committees in Dental Teaching Institutions in Kerala, India. AB - OBJECTIVES: To assess the existence, structure, and functioning of Institutional Ethics Committees (IECs) in dental teaching institutions in Kerala. METHODOLOGY: A cross-sectional questionnaire-based survey was conducted by personally approaching Heads of Institutions/Ethics Committee (EC) in-charge of all dental colleges (23) in Kerala. The validated questionnaire consisted of two parts. The first part pertained to details of institutions, and the second part assessed the structure and functioning of the IEC. The data obtained was tabulated and analyzed using descriptive statistics. RESULTS: Of the participating 17 colleges, 13 colleges had a functioning IEC. Only four of these IECs were accredited to a central agency. Only one among the 12 colleges completely adhered to recommended structure. Regarding the functioning of IECs, 69% of the IECs had neither a separate application form for ethical review of proposals nor a proforma for its evaluation. On average, more than ten proposals were reviewed in a single EC meeting in 54% of the colleges. Nearly 40% of the IECs had no representation of a lay person. CONCLUSION: The absence of IEC in four colleges and non-accreditation to a central agency was a matter of concern. Enforced accreditation is the need of the hour to ensure ethical protection to human participants. PMID- 26549797 TI - gammadelta T cells support gut Ag-reactive colitogenic effector T-cell generation by enhancing Ag presentation by CD11b(+) DCs in the mesenteric LN. AB - T cells expressing the gammadelta TCR are dominant T-cell subsets in the intestinal immune system. We previously demonstrated that gammadelta T cells play important roles in augmenting Th17-type colitogenic immune responses in a T-cell induced colitic inflammation model. However, its underlying mechanism remains poorly understood. In this study, an in vitro coculture system using effector T cells enriched in gut Ag-reactive cells was employed as a readout tool to search for gut Ag presenting APCs. We found that the presence of gammadelta T cells dramatically enhances gut Ag presentation within the mLN in mice. Gut Ag presentation by CD11b(+) DC subsets was particularly controlled by gammadelta T cells. Interestingly, gammadelta T-cell entry to the lymph nodes was essential to improve the Ag presentation. Therefore, our results highlight that gammadelta T cells play a previously unrecognized role to support colitogenic immunity by regulating gut Ag presentation in the draining LN. PMID- 26549798 TI - Does Spatial Access to Mammography Have an Effect on Early Stage of Breast Cancer Diagnosis? A county-level Analysis for New York State. PMID- 26549799 TI - Prognostic Impact and Late Evolution of Untreated Moderate (2/4+) Functional Tricuspid Regurgitation in Patients Undergoing Aortic Valve Replacement. AB - OBJECTIVES: The aim of the present study was to evaluate the prognostic impact and late evolution of associated tricuspid regurgitation (TR) 2/4+ after aortic valve replacement (AVR). METHODS: We evaluated 61 patients who underwent AVR between 2003 and 2012 (35 for aortic stenosis [AS], 26 for aortic regurgitation [AR]) with associated untreated TR 2/4+. Patients with concomitant mitral disease were excluded. Median follow-up was 3.2 years. Serial echocardiographic and clinical data were collected and analyzed. RESULTS: Mean age was 65 +/- 13 years; 26% of the patients were in NYHA class III-IV. Left ventricular ejection fraction was 53 +/- 11%. Comorbidity included: chronic obstructive pulmonary disease in 5%, chronic renal failure in 13%, coronary artery disease in 20%, history of stroke/TIA in 8%. Thirty-day mortality was 1.6%. Overall actuarial survival was 83 +/- 6% at 6.5 years, with a freedom from cardiac death of 90 +/- 5%. Freedom from TR >=3+ was 86 +/- 6% at 6.5 years. At last follow-up, 82% of the patients had TR 0-1/4+, 9% had TR 2/4+, 4.5% had TR 3/4+ and 4.5% had TR 4/4+. Occurrence of TR >= 3+ at follow-up was associated with increased cardiac mortality (HR 10.5; p = 0.009). CONCLUSIONS: preoperative untreated TR 2/4+ improves or remains stable in the majority of patients. The poor outcomes associated with TR > 2+ suggest the need for better methods to identify subjects at risk for TR progression. PMID- 26549802 TI - Validation of modeled pharmacoeconomic claims in formulary submissions. AB - Modeled or simulated claims for costs and outcomes are a key element in formulary submissions and comparative assessments of drug products and devices; however, all too often these claims are presented in a form that is either unverifiable or potentially verifiable but in a time frame that is of no practical use to formulary committees and others who may be committed to ongoing disease-area and therapeutic-class reviews. On the assumption that formulary committees are interested in testable predictions for product performance in target populations and ongoing disease area and therapeutic reviews, the methodological standards that should be applied are those that are accepted in the natural sciences. Claims should be presented in a form that is amenable to falsification. If not, they have no scientific standing. Certainly one can follow ISPOR-SMDM standards for validating the assumptions underpinning a model or simulation. There is clearly an important role for simulations as an input to policy initiatives and developing claims for healthcare interventions and testable hypotheses; however, one would not evaluate such claims on the realism or otherwise of the model. The only standard is one of the model's ability to predict outcomes successfully in a time frame that is practical and useful. No other standard is acceptable. This sets the stage for an active research agenda. PMID- 26549800 TI - Molecular mechanisms regulating NLRP3 inflammasome activation. AB - Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1beta. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inflammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome. PMID- 26549801 TI - Magnesium ion influx reduces neuroinflammation in Abeta precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin 1beta. AB - Alzheimer's disease (AD) has been associated with magnesium ion (Mg2+) deficits and interleukin-1beta (IL-1beta) elevations in the serum or brains of AD patients. However, the mechanisms regulating IL-1beta expression during Mg2+ dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1beta reduction using a recently developed compound, magnesium-L-threonate (MgT). Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system, we delineated the signaling pathways by which MgT suppressed the expression of IL-1beta in glial cells. In detail, we found that MgT incubation stimulated the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and peroxisome proliferator-activated receptor gamma (PPARgamma) signaling pathways by phosphorylation, which resulted in IL-1beta suppression. Simultaneous inhibition of the phosphorylation of ERK1/2 and PPARgamma induced IL 1beta upregulation in MgT-stimulated glial cells. In accordance with our in vitro data, the intracerebroventricular (i.c.v) injection of MgT into the ventricles of APP/PS1 transgenic mice and treatment of Abeta precursor protein (APP)/PS1 brain slices suppressed the mRNA and protein expression of IL-1beta. These in vivo observations were further supported by the oral administration of MgT for 5 months. Importantly, Mg2+ influx into the ventricles of the mice blocked the effects of IL-1beta or amyloid beta-protein oligomers in the cerebrospinal fluid. This reduced the stimulation of IL-1beta expression in the cerebral cortex of APP/PS1 transgenic mice, which potentially contributed to the inhibition of neuroinflammation. PMID- 26549803 TI - Gingival crevicular fluid vascular endothelial cell growth factor and platelet derived growth factor-BB release profile following the use of perforated barrier membranes during treatment of intrabony defects: a randomized clinical trial. AB - BACKGROUND AND OBJECTIVE: Perforated barrier membranes open channels between the suprabony and intrabony compartments of the defect, which could allow for more physiologic cellular interactions between different components of the periodontium during guided tissue regeneration surgery. To test this assumption, this study was designed to evaluate levels of vascular endothelial cell growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in gingival crevicular fluid during the early stages of healing of localized intrabony defects treated with perforated membranes (PMs) or non-PMs, as compared with open flap debridement. MATERIAL AND METHODS: Thirty non-smoking patients with severe chronic periodontitis participated in this prospective, randomized and single blinded trial. Each patient contributed one interproximal defect that was randomly assigned to the PM group (n = 10), occlusive membrane (OM) group (n = 10) or open flap debridement (OFD) group (n = 10). Plaque index, gingival index, probing depth, clinical attachment level and the intrabony depth of the defect were measured at baseline and reassessed at 6 and 9 mo after therapy. Gingival crevicular fluid samples were collected on days 1, 3, 7, 14, 21 and 30 d after therapy for the changes in VEGF and PDGF-BB levels. RESULTS: During the early stages of healing (1, 3 and 7 d), the mean VEGF and PDGF-BB concentrations at sites treated with PMs and OFD peaked with a statistically significant difference as compared with the OM-treated group. VEGF and PDGF-BB levels at sites treated with PMs and OFD were not statistically different. Growth factor levels decreased sharply in the samples obtained at days 21 and 30 with non-significant differences between the three groups. Nine months after therapy, the PM-treated group showed a statistically significant improvement in probing depth, clinical attachment level and intrabony defect compared to the OM and OFD groups. CONCLUSIONS: Within the limits of the present study, one can conclude that PM coverage of periodontal defects is associated with initial gingival crevicular fluid growth factor upregulation that could improve the clinical outcomes of guided tissue regeneration surgery. PMID- 26549804 TI - Relation of infant motor development with nonverbal intelligence, language comprehension and neuropsychological functioning in childhood: a population-based study. AB - Within a population-based study of 3356 children, we investigated whether infant neuromotor development was associated with cognition in early childhood. Neuromotor development was examined with an adapted version of Touwen's Neurodevelopmental Examination between 9 and 20 weeks. Parents rated their children's executive functioning at 4 years. At age 6 years, children performed intelligence and language comprehension tests, using Dutch test batteries. At age 6-9 years, neuropsychological functioning was assessed in 486 children using the validated NEPSY-II-NL test battery. We showed that less optimal neurodevelopment in infancy may predict poor mental rotation, immediate memory, shifting, and planning; but not nonverbal intelligence or language comprehension. PMID- 26549805 TI - CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype. AB - Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research. PMID- 26549807 TI - Integrated approach to understanding the onset and pathogenesis of black band disease in corals. AB - Emerging infectious diseases are contributing to global declines in coral reef ecosystems, highlighting a growing need for aetiological knowledge to develop effective management strategies. In this review, we focus on black band disease (BBD), one of the most virulent diseases and the only polymicrobial disease so far known to affect corals. A multipartite microbial consortium dominated by Cyanobacteria, but also including sulfur-cycling bacteria, other bacterial groups and members of the Archaea and Eukarya, forms a sulfide-rich anaerobic mat that migrates across the surface of coral colonies, killing the underlying tissues. The polymicrobial nature of the disease challenges classic aetiological approaches to unravelling disease causation. Here, we synthesize current knowledge on the range of pathogens forming the microbial consortium with recent studies on the transmission, biogeochemistry and environmental drivers of BBD to develop a conceptual model of BBD pathogenesis. The model illustrates how the development of BBD virulence factors is linked to a cascade of microbial community shifts and associated functional roles that progressively develop the microbial consortium from comparatively benign cyanobacterial patches to virulent BBD lesions. This review showcases how an approach that integrates multiple key aspects of the disease provides insights essential to elucidating the aetiology of BBD. PMID- 26549806 TI - Glycyrrhetinic acid induces cytoprotective autophagy via the inositol-requiring enzyme 1alpha-c-Jun N-terminal kinase cascade in non-small cell lung cancer cells. AB - Glycerrhetinic acid (GA), one of the main bioactive constituents of Glycyrrhiza uralensis Fisch, exerts anti-cancer effects on various cancer cells. We confirmed that GA inhibited cell proliferation and induced apoptosis in non-small cell lung cancer A549 and NCI-H1299 cells. GA also induced expression of autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and punta formation of green fluorescent protein microtubule-associated protein light-chain 3. We further proved that expression of GA-increased autophagy marker was attributed to activation instead of suppression of autophagic flux. The c-jun N-terminal kinase (JNK) pathway was activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. The endoplasmic reticulum (ER) stress responses were also apparently stimulated by GA by triggering the inositol-requiring enzyme 1alpha (IRE1alpha) pathway. The GA induced JNK pathway activation and autophagy were decreased by IRE1alpha knockdown, and inhibition of autophagy or the JNK cascade increased GA-stimulated IRE1alpha expression. In addition, GA-induced cell proliferative inhibition and apoptosis were increased by inhibition of autophagy or the JNK pathway. Our study was the first to demonstrate that GA induces cytoprotective autophagy in non small cell lung cancer cells by activating the IRE1alpha-JNK/c-jun pathway. The combined treatment of autophagy inhibitors markedly enhances the anti-neoplasmic activity of GA. Such combination shows potential as a strategy for GA or GA contained prescriptions in cancer therapy. PMID- 26549808 TI - A Single-Center Experience of Aortic and Iliac Artery Aneurysm Treated with Multilayer Flow Modulator. AB - BACKGROUND: The aim of this study was to analyze our series of endovascular treatments using a multilayer flow modulator (MFM) and to show the midterm results. METHODS: At our institution, 8 patients were treated with an MFM. Four patients presented with an aortic aneurysm (2 type II thoracoabdominal aortic aneurysms [TAAAs], 1 type IV TAAA, and 1 juxtarenal abdominal aortic aneurysm) and 4 with an aneurysm involving the common iliac artery. Mortality, rupture and secondary intervention, major complications, patency of collateral vessels, and volume analysis were evaluated. Treated patients were followed up with computed tomography angiography at 1, 3, 6, and 12 months. RESULTS: Results showed no 30 day mortality or major complications; technical success was achieved in 87.5% of patients, patency of collateral vessels was reached in all cases at intraoperative completion angiography. Mean follow-up was 22.1 months (range, 18 30), survival rate was 87.5%, and one case of death unrelated to MFM treatment was reported. During follow-up, MFM and collateral vessel patency were observed in all cases. Secondary endovascular or open surgical procedures were not needed during follow-up. Volume analysis showed a slight increase in patients with aortic aneurysm, and an overall trend to increase in thrombosis was observed in all cases. CONCLUSIONS: Endovascular treatment of aneurysms with MFM seems to have encouraging midterm results. Should our results be confirmed by larger series and longer follow-up studies, MFM may become a viable alternative to other endovascular approaches. PMID- 26549809 TI - Contemporary Outcomes for Open Infrainguinal Bypass in the Endovascular Era. AB - BACKGROUND: The role of infrainguinal bypasses in this era of increasing endovascular interventions remains the subject of significant debate. In this study, we evaluate contemporary long-term outcomes of lower-extremity open revascularization for peripheral arterial disease (PAD). METHODS: We evaluated all patients who underwent infrainguinal bypass with autogenous vein conduits for claudication or critical limb ischemia in our institution between January 1st, 2007 and July 31st, 2014. Kaplan-Meier and Cox regression analyses were used to evaluate graft failure and identify its predictors. Outcomes were defined per the Society for Vascular Surgery standards. RESULTS: There were 428 autogenous vein grafts (femoro-popliteal: 32%, femoro-tibial: 39%, popliteo-tibial: 27%, and tibio-tibial: 2%) placed in 368 patients (mean age of 67 +/- 11.4 years). Most patients were male (59%), white (73%), and presented with critical limb ischemia (81%). Sixty-five cases (15%) were redo bypasses. Arm veins and spliced vein conduits were used in 15% and 14% of cases, respectively. Primary patency at 1, 3, and 5 years was 66%, 59%, and 55%, respectively. Primary-assisted patency was 78%, 69%, and 64% at 1, 3, and 5 years, respectively. Secondary patency was 88%, 84%, and 82% at 1, 3, and 5 years, respectively. Patency was higher for grafts harvested from the lower versus upper extremities and for proximal versus distal bypass (all P < 0.05). Limb salvage rate was 88% after a mean follow-up of 2 +/- 1.8 years. Significant predictors of graft failure were younger age, diabetes mellitus, and hyperlipidemia (all P < 0.05). CONCLUSIONS: In this contemporary cohort of patients, we have demonstrated that infrainguinal bypass for lower extremity revascularization has good long-term outcomes in patients with symptomatic PAD. Patency and limb salvage rates are optimized with careful selection of autogenous conduits, close monitoring of high-risk groups and management of comorbidities. PMID- 26549810 TI - Thrombomodulin Induces a Quiescent Phenotype and Inhibits Migration in Vascular Smooth Muscle Cells In Vitro. AB - BACKGROUND: Loss of critical endothelial cell function and subsequent vascular smooth muscle cell (VSMC) migration is central to the pathology of injury-induced neointimal hyperplasia and recurrent stenosis. Thrombomodulin (TM), well known for its function as an endothelial surface anticoagulant, may have an unknown direct effect on VSMC physiology that would be lost after injury. Here, we examined a novel effect of TM on VSMC by testing the hypothesis that direct application of TM induces favorable changes to the morphology of VSMC and inhibits their migration. METHODS: Primary human VSMC were harvested using the explant technique and used in early passage (1-4) for all experiments. Laser scanning confocal fluorescent imaging was performed to assess the effect of soluble TM on VSMC morphology. In vitro, migration of VSMC was measured using: (1) a 4-hr modified Boyden chemotaxis assay and (2) a 24-hr electric cell substrate impedance sensing injury migration assay. Migration experiments were conducted with VSMC exposed to increasing doses of soluble recombinant TM. Recombinant thrombin served as a positive control and serum-free media as a negative control for all experimentation. Data were analyzed using a Student's t test or repeated measures analysis of variance where appropriate (alpha < 0.05). RESULTS: VSMC exposed to TM clearly demonstrated a quiescent morphology with organized stress fibers consistent with a quiescent, differentiated, contractile phenotype; whereas, thrombin stimulation led to an activated, dedifferentiated, synthetic phenotype. VSMC demonstrated a low, baseline level of migration in unstimulated serum-free conditions. Thrombin significantly stimulated VSMC migration as expected. TM, independent of thrombin, significantly inhibited baseline VSMC migration in a dose-response fashion. The maximal inhibition was observed at (5 MUg/mL) with 70% reduction (56 +/- 1.7 vs. 18 +/- 3.5 cells/5 high power fields, P = 0.0005). CONCLUSIONS: TM has a direct effect on VSMC resulting in a quiescent, differentiated and contractile phenotype, and inhibition of migration. This effect is independent of the presence of thrombin. These findings provide new knowledge in understanding the pathophysiology of vascular injury and support a strategy focused on restoring key endothelial function to prevent intimal hyperplasia. PMID- 26549811 TI - Amputation Rates for Patients with Diabetes and Peripheral Arterial Disease: The Effects of Race and Region. AB - BACKGROUND: It remains unknown whether care of high-risk vascular patients with both diabetes and peripheral arterial disease (PAD) is improving. We examined national trends in care of patients with both PAD and diabetes. METHODS: A cohort of patients diagnosed with PAD and diabetes between 2007 and 2011 undergoing open or endovascular diagnostic or revascularization procedures was analyzed using Medicare claims data. Main outcome measure was amputation-free survival measured from time of initial revascularization procedure to 24 months, stratified by race and hospital referral region (HRR). RESULTS: From 2007 to 2011, 2.3 per 1,000 patients underwent a major amputation with the higher rate among black patients (5.5 per 1,000 vs. 1.9 per 1,000; P < 0.001) compared with nonblack. The rate varied widely by HRR (1.2 per 1,000-6.2 per 1,000), with higher variation in amputation rates in black patients (2.1-16.1 per 1,000). Overall, amputation-free survival was approximately 74.6% at 2 years, 68.4% among black patients, and 75.4% among nonblack patients, with the disparity between the 2 groups increasing over time. CONCLUSIONS: Prevalence of concurrent PAD and diabetes is increasing, but amputation rates and amputation-free survival vary significantly by both race and HRR. Prevention and care coordination effort should aim to limit racial disparities in the treatment and outcomes of these high-risk patients. PMID- 26549812 TI - Modelling the structure of sludge aggregates. AB - The structure of sludge is closely associated with the process of wastewater treatment. Synthetic dyestuff wastewater and sewage were coagulated using the PAX and PIX methods, and electro-coagulated on aluminium electrodes. The processes of wastewater treatment were supported with an organic polymer. The images of surface structures of the investigated sludge were obtained using scanning electron microscopy (SEM). The software image analysis permitted obtaining plots log A vs. log P, wherein A is the surface area and P is the perimeter of the object, for individual objects comprised in the structure of the sludge. The resulting database confirmed the 'self-similarity' of the structural objects in the studied groups of sludge, which enabled calculating their fractal dimension and proposing models for these objects. A quantitative description of the sludge aggregates permitted proposing a mechanism of the processes responsible for their formation. In the paper, also, the impact of the structure of the investigated sludge on the process of sedimentation, and dehydration of the thickened sludge after sedimentation, was discussed. PMID- 26549813 TI - Broadband and enhanced nonlinear optical response of MoS2/graphene nanocomposites for ultrafast photonics applications. AB - Due to their relatively high compatibility with specific photonic structures, strong light-matter interactions and unique nonlinear optical response, two dimensional (2D) materials, such as graphene and transition metal dichalcogenides, are attractive for ultrafast photonics applications. Here, we fabricate MoS2/graphene nanocomposites by a typical hydrothermal method. In addition, we systematically investigate their nonlinear optical responses. Our experiments indicate that the combined advantages of ultrafast relaxation, a broadband response from graphene, and the strong light-matter interaction from MoS2, can be integrated together by composition. The optical properties in terms of carrier relaxation dynamics, saturation intensity and modulation depth suggest great potential for the MoS2/graphene nanocomposites in photonics applications. We have further fabricated 2D nanocomposites based optical saturable absorbers and integrated them into a 1.5 MUm Erbium-doped fiber laser to demonstrate Q switched and mode-locked pulse generation. The fabrication of 2D nanocomposites assembled from different types of 2D materials, via this simple and scalable growth approach, paves the way for the formation and tuning of new 2D materials with desirable photonic properties and applications. PMID- 26549814 TI - Comparative analysis of peptidoglycan recognition proteins in endoparasitoid wasp Microplitis mediator. AB - Peptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characterized six PGRPs from endoparasitoid wasp, Microplitis mediator (MmePGRPs). To understand the roles of PGRPs in parasitoid wasps, we analyzed their evolutionary relationship and orthology, expression profiles during different developmental stages, and transcriptional expression following infection with Gram-positive and -negative bacteria and a fungus. MmePGRP-S1 was significantly induced in response to pathogenic infection. This prompted us to evaluate the effects of RNA interference mediated gene specific knockdown of MmePGRP-S1. The knockdown of MmePGRP-S1 (iMmePGRP-S1) dramatically affected wasps' survival following challenge by Micrococcus luteus, indicating the involvement of this particular PGRP in immune responses against Gram-positive bacteria. This action is likely to be mediated by the Toll pathway, but the mechanism remains to be determined. MmePGRP-S1 does not play a significant role in anti-fungal immunity as indicated by the survival rate of iMmePGRP-S1 wasps. This study provides a comprehensive characterization of PGRPs in the economically important hymenopteran species M. mediator. PMID- 26549815 TI - Long-term cognitive sequelae in a case of Wernicke's encephalopathy after allogeneic stem cell transplantation. AB - We describe the case of a non-alcoholic patient with chronic myeloid leukemia who developed iatrogenic Wernicke's encephalopathy (WE) following stem cell transplantation. Four years after the WE acute event, the patient's cognitive profile was mainly characterized by moderate memory impairment, and functional and daily-living difficulties. Our report sustains the hypothesis that a iatrogenic form of WE may produce long-term cognitive sequelae even when thiamine therapy is administered in the acute phase until the resolution of the neurological signs. PMID- 26549816 TI - Ethanol extract of Kalopanax septemlobus leaf induces caspase-dependent apoptosis associated with activation of AMPK in human hepatocellular carcinoma cells. AB - The Kalopanax septemlobus leaf (Thunb.) Koidz. has been used as a traditional medicine herb for the treatment of various human diseases for hundreds of years. In this study, we investigated the mechanism underlying the inhibitory effects of an ethanol extract of K. septemlobus leaf (EEKS) on proliferation of HepG2 hepatocellular carcinoma cells. For this study, cell viability and apoptosis were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, DAPI (4,6-diamidino-2-phenylindole) staining, agarose gel electrophoresis, and flow cytometry. Measurements of the mitochondrial membrane potential (MMP), caspase activity assays and western blots were conducted to determine whether HepG2 cell death occurred by apoptosis. Treatment of HepG2 cells with EEKS concentration-dependently reduced cell survival while significantly increasing the ratio of apoptotic cells. EEKS treatment increased the levels of the death receptors (DRs), DR4 and DR5, and activated caspases, as well as promoting proteolytic degradation of poly(ADP-ribose)-polymerase associated with the downregulation of protein expression of members of the inhibitor of apoptosis protein family. Treatment with EEKS also caused truncation of Bid, translocation of pro-apoptotic Bax to the mitochondria, and loss of mitochondrial membrane permeabilization, thereby inducing the release of cytochrome c into the cytosol. However, treatment of HepG2 cells with a pan caspase inhibitor reversed EEKS-induced apoptosis and growth suppression, indicating that EEKS appears to induce apoptosis though a caspase-dependent mechanism involving both intrinsic and extrinsic apoptotic pathways. In addition, the phosphorylation level of AMP-activated protein kinase (AMPK) was elevated when cells were exposed to EEKS. A specific inhibitor for AMPK attenuated the EEKS-induced activation of caspases, and consequently prevented the EEKS-induced apoptosis and reduction in cell viability. Overall, our findings suggest that EEKS inhibits the growth of HepG2 cells by inducing AMPK-mediated caspase dependent apoptosis, suggesting the potential therapeutic application of EEKS in the treatment or prevention of cancers. PMID- 26549817 TI - Phasor Representation of Monomer-Excimer Kinetics: General Results and Application to Pyrene. AB - Phasor plots of the fluorescence intensity decay (plots of the Fourier sine transform versus the Fourier cosine transform, for one or several angular frequencies) are being increasingly used in studies of homogeneous and heterogeneous systems. In this work, the phasor approach is applied to monomer excimer kinetics. The results obtained allow a clear visualization of the information contained in the decays. The monomer phasor falls inside the universal circle, whereas the excimer phasor lies outside it, but within the double-exponential outer boundary curve. The monomer and excimer phasors, along with those corresponding to the two exponential components of the decays, fall on a common straight line and obey the generalized lever rule. The clockwise trajectories described by both phasors upon monomer concentration increase are identified. The phasor approach allows discussing in a single graphic not only the effect of concentration but also that of rate constants, including the evolution from irreversible kinetics to fast excited-state equilibrium upon a temperature increase. The obtained results are applied to the fluorescence decays of pyrene monomer and excimer in methylcyclohexane at room temperature. A straightforward method of monomer-excimer lifetime data analysis based on linear plots is also introduced. PMID- 26549818 TI - Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target. AB - BACKGROUND: Integrin-linked kinase (ILK) is a serine-threonine kinase that regulates interactions between the cell and the extracellular matrix. In many cancers, overexpression of ILK leads to increased cell proliferation, motility, and invasion. We hypothesized that ILK functions as a regulator of viability and migration in thyroid cancer cells. METHODS: Eleven human thyroid cancer cell lines were screened for ILK protein expression. The cell lines with the greatest expression were treated with either ILK small interfering RNA (siRNA) or a novel ILK inhibitor, T315, and the effects were evaluated via Western blot and migration assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays were performed to assess cell viability. RESULTS: siRNA against ILK decreased phosphorylation of downstream effectors Akt and MLC, as well as decreased migration. Treatment with T315 showed a dose-related decrease in both Akt and MLC phosphorylation, as well as decreased migration. 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays showed T315 to have an half maximal inhibitory concentration of less than 1 MUM in cell lines with high ILK expression. CONCLUSION: ILK is expressed differentially in thyroid cancer cell lines. Both ILK siRNA and T315 inhibit motility of thyroid cancer cell lines, and T315 is shown to be cytotoxic at low concentrations. Altogether, our study suggests that ILK may represent an important kinase in aggressive thyroid cancers. PMID- 26549819 TI - Randomized controlled clinical trial comparing radioguided occult lesion localization with wire-guided lesion localization to evaluate their efficacy and accuracy in the localization of nonpalpable breast lesions. AB - PURPOSE: The aim of this study was to compare the radioguided occult lesion localization (ROLL) technique with the wire-guided lesion localization (WGLL) technique to assess their efficacy and accuracy in the localization of nonpalpable breast lesions in patients at a unique reference medical center. These patients' reports were negative for malignancy but included highly suspicious imaging findings. METHODS: A controlled clinical trial was designed to compare the WGLL and ROLL techniques in women presenting with breast lesions diagnosed by mammography or ultrasonography at the Instituto Nacional de Cancerologia in Bogota, Colombia, from March 2006 to June 2011. RESULTS: This study examined 129 patients; 64 (49.6%) patients were treated with ROLL, and 65 (51.4%) were treated with WGLL. The ROLL technique achieved better median lesion centricity (ROLL = 11.7 and WGLL = 15.4; P = .038). No significant differences were found regarding demographic variables, operative specimen characteristics, the need to extend margins, operative complications, the degree of difficulty, or patient or surgeon satisfaction. CONCLUSION: The ROLL technique is as effective as WGLL for the localization of nonpalpable breast lesions. In our study, ROLL achieved better lesion centricity. Therefore, we propose that this technique could be used as a standard procedure in the detection of nonpalpable breast lesions at experienced centers. PMID- 26549820 TI - Discussion. PMID- 26549821 TI - Poorer Subjective Sleep Quality Is Related to Higher Fantasy-Induced Sexual Arousal in Women of Reproductive Age. AB - Lack of sleep enhances erections and lubrication the next day. This raises the possibility that poorer subjective sleep quality is related to sexual arousal. To test this hypothesis, sexual arousal was elicited in 70 Portuguese women of reproductive age by means of fantasy. The level of salivary testosterone before and shortly after fantasy was determined by luminescence immunoassays. Participants completed the Pittsburgh Sleep Quality Index (PSQI), reported their sexual arousal before and during fantasy, and how anxious they were after the fantasy. The hypothesis was confirmed. Anxiety did not explain the association, but testosterone response (poststimulus minus baseline) had a slight explanatory effect. PMID- 26549822 TI - Adverse drug reactions in children: a ten-year review of reporting to the Portuguese Pharmacovigilance System. AB - OBJECTIVE: Adverse drug reactions (ADR) are a public health problem. They cause significant morbidity, mortality and health costs. Less is known about pediatric ADR. Our goal was to characterize a pediatric case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) during the past 10 years. RESEARCH DESIGN AND METHODS: Retrospective analysis of ADR reports concerning patients till 17 years old received by the PPS between 2003 and 2012. We evaluated patients' demographic data and involved drugs, as well as characteristics and seriousness of reactions, stratified by age groups. RESULTS: We found 1742 reports (50% females) corresponding to 9.7% of the total received. The age of the patients varied from 0 to 17 years (median: 5 years, interquartile range: 10.6), with 566 cases (32%) occurring in patients younger than 2y. Among the 1195 serious cases, 31% (370) episodes led to hospitalization. In 32 cases (2%) there was a fatal outcome. Most of the ADR reported referred to general disorders and administration site conditions, followed by skin and subcutaneous tissue reactions. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (17%). CONCLUSIONS: Pediatric ADR represents about 10% of the reports received by the PPS. Most ADR were considered serious. Major findings varied according to age groups. PMID- 26549823 TI - Malignant Transformation of Teratoma to Adenocarcinoma With Complete Remission With All-Trans Retinoic Acid-Based Treatment and Surgery. PMID- 26549824 TI - A Drug Interaction Between Cabozantinib and Warfarin in a Patient With Renal Cell Carcinoma. PMID- 26549825 TI - Solvent and Substituent Effects on the Aggregation Behavior of Surface-Active Ionic Liquids with Aromatic Counterions and the Dispersion of Carbon Nanotubes in their Hexagonal Liquid Crystalline Phase. AB - The aggregation behavior of surface-active ionic liquids (SAILs) 1-dodecyl-3 methylimidazolium m- and p-hydroxybenzoate (m-C12mimHB and p-C12mimHB) in water and ethylammonium nitrate (EAN) was investigated. Surface tension measurements indicate that the cmc values of SAILs in EAN are much higher than those in water, resulting from the weaker solvophobic effect of EAN, and the stronger stability of SAILs/EAN complexes proven by DFT calculations. Compared to 1-dodecyl-3 methylimidazolium salicylate (C12mimSal), the effect of substituent position leads to weaker interactions between aromatic counterions and headgroups. The hexagonal liquid crystal (H1) phase formed by C12mimHB in water or EAN at a higher concentration was determined by polarized optical microscopy (POM), small angle X-ray scattering (SAXS), and rheology techniques. Structural parameters estimated from SAXS curves suggest that the higher SAILs concentration or temperature leads to a smaller lattice parameter (a0) and a denser arrangement of cylinders. For C12mimHB, the formation of the H1 phase in H2O is easier than that in EAN. Furthermore, compared to C12mimSal, C12mimHB exists over a broad region of the hexagonal liquid crystalline (H1) phase, which is due to the different position of the substituents on the aromatic ring of counterions. Therefore, the H1 phase of the lypotropic liquid crystals (LLCs) formed in the C12mimHB/H2O system exhibits excellent performance in uniformly dispersing multiwalled carbon nanotubes (MWCNTs). Increasing the concentration of MWCNTs results in a larger lattice parameter (a0) value, indicating the integration of MWCNTs within the cylinders of the H1 phase. The rheological measurement results demonstrate that MWCNTs/LLCs composites are highly viscoelastic, and the presence of MWCNTs obviously strengthens the apparent viscosity of the H1 phase. PMID- 26549826 TI - Spatial frequency heterodyne imaging of aqueous phase transitions inside multi walled carbon nanotubes. AB - The evaporation and condensation of water on multi-walled carbon nanotube (MWCNT) surfaces was studied as a function of temperature and time using X-ray spatial frequency heterodyne imaging (SFHI). SFHI is an imaging modality that produces an absorption and scatter image in a single exposure, and has increased sensitivity to variations in electron density relative to more common place X-ray imaging techniques. Differing features exhibited in the temporal scatter intensity profiles recorded during evaporation and condensation revealed the existence of an absorption-desorption hysteresis. Effects on the aforementioned phenomena due to chemical functionalization of the carbon nanotube surfaces were also monitored. The increased interaction potential between the functionalized MWCNT walls and water molecules altered the evaporation event time scale and increased the temperature at which condensation could take place. Theoretical calculations were used to correlate the shape of the observed scatter profiles during condensation to changes in the MWCNT cross section geometry and configuration of the contained water volume. Changes in evaporation time scales with temperature coincided with the boiling point for confined water predicted by the Kelvin equation, indicating that a thermodynamic description of mesoscopic confined water is permissible in some instances. PMID- 26549827 TI - A simple and controllable graphene-templated approach to synthesise 2D silica based nanomaterials using water-in-oil microemulsions. AB - Using the versatility of silica chemistry, we describe herein a simple and controllable approach to synthesise two-dimensional (2D) silica-based nanomaterials: the diversity and utility of the resulting structures offer excellent platforms for many potential applications. PMID- 26549828 TI - Characteristics of audiogram configuration in multiple-system atrophy C and cortical cerebellar atrophy. AB - CONCLUSION: The prevalence of low-tone hearing loss (LTHL) is significantly high in spinocerebellar degeneration (SCD) with cerebellar predominance, including multiple-system atrophy C (MSA-C) and cortical cerebellar atrophy (CCA). OBJECTIVE: This study aimed to test the hypothesis that SCD with cerebellar predominance, MSA-C and CCA may cause auditory symptoms. METHODS: The shape and threshold of pure-tone audiograms were evaluated for MSA-C (n = 47; mean (+/- SD) age, 61.6 +/- 8.9 years), CCA (n = 16; 62.8 +/- 9.5 years), and age-matched controls (n = 169; 62.5 +/- 10.7 years). To differentiate specific hearing loss for MSA-C and CCA from presbycusis, the shape of audiograms was examined based on previously established audiological criteria. RESULTS: When audiogram shape was defined according to audiological criteria, the odds ratio for LTHL in SCD compared to controls was 2.492 (95% confidence interval (CI) = 1.208-5.139; p < 0.05, Pearson's Chi-square test) in MSA-C and 2.194 (95% CI = 0.709-6.795) in CCA. When the selection of audiogram shape according to these criteria was verified by three certified audiologists, odds ratios for LTHL in MSA-C and CCA were 3.243 (95% CI = 1.320-7.969) and 3.692 (95% CI = 1.052-12.957), respectively, significantly higher than in controls. PMID- 26549829 TI - A simple cytogenetic method to detect chromosomally integrated human herpesvirus 6. AB - Some healthy individuals carry human herpesvirus-6 (HHV-6) within a host chromosome, which is called inherited chromosomally integrated human herpesvirus 6 (iciHHV-6). Because iciHHV-6 is generally considered a non-pathogenic condition, it is important to distinguish iciHHV-6 from HHV-6 reactivation in immunocompromised hosts because both conditions manifest high copy numbers of the HHV-6 in peripheral blood mononuclear cells. Although fluorescent in situ hybridization (FISH) is a reliable method for the diagnosis of iciHHV-6, HHV-6 specific FISH probes are not commercially available. In our present study, we established a simple PCR-based method for producing FISH probes that can detect the chromosomal integration site of iciHHV-6 at high sensitivity. Using these probes, we confirmed that HHV-6 signals were consistently located at the telomeric region in all of the 13 iciHHV-6 individuals examined. Interestingly, in all seven Japanese iciHHV-6A patients, signals were detected exclusively on chromosome 22q. This method provides a simple and fast approach for iciHHV-6 diagnosis in the clinical laboratory. PMID- 26549830 TI - Phosphorproteome Changes of Myofibrillar Proteins at Early Post-mortem Time in Relation to Pork Quality As Affected by Season. AB - The effect of season on phosphorylation of myofibrillar proteins and meat quality of pork longissimus muscles was investigated. Muscle samples were obtained from 40 pork carcasses (10 for each season) at 45 min and 3 and 9 h post-mortem. Myofibrillar proteins were extracted, separated by SDS-PAGE, quantified by phosphor-specific staining, and finally identified by LC-MS/MS. Muscle pH, glycogen, and ATP were measured, and pale, soft, and exudative (PSE) meat was identified by pH value at 45 min post-mortem. A total of 23 bands were detected on SDS-PAGE gels. The phosphorylation levels of bands did not differ between PSE and normal meat. However, the phosphorylation levels of 22 bands were significantly changed by season. Nine of them showed different changes from 45 min to 9 h post-mortem, which were identified to be involved in energy metabolism and sarcomere contraction. Correlation analysis indicated the regulatory progress of these proteins during rigor mortis. These observations contribute to a better understanding of the biochemical processes for the conversion of muscle to meat varying with season. PMID- 26549831 TI - The opinions of occupational physicians about maintaining healthy workers by means of medical examinations in Japan using the Delphi method. AB - OBJECTIVES: In Japan, employee fitness for work is determined by annual medical examinations. It may be possible to reduce the variability in the results of work fitness determination, particularly for situation, if there is consensus among experts regarding consideration of limitation of work by means of a single parameter. METHODS: Consensus building was attempted among 104 occupational physicians by employing a 3-round Delphi method. Among the medical examination parameters for which at least 50% of participants agreed in the 3rd round of the survey that the parameter would independently merit consideration for limitation of work, the values of the parameters proposed as criterion values that trigger consideration of limitation of work were sought. Parameters, along with their most frequently proposed criterion values, were defined in the study group meeting as parameters for which consensus was reached. RESULTS: Consensus was obtained for 8 parameters: systolic blood pressure 180 mmHg (86.6%), diastolic blood pressure 110 mmHg (85.9%), postprandial plasma glucose 300 mg/dl (76.9%), fasting plasma glucose 200 mg/dl (69.1%), Cre 2.0mg/dl (67.2%), HbA1c (JDS) 10% (62.3%), ALT 200 U/l (61.6%), and Hb 8 g/l (58.5%). CONCLUSIONS: To support physicians who give advice to employers about work-related measures based on the results of general medical examinations of employees, expert consensus information was obtained that can serve as background material for making judgements. It is expected that the use of this information will facilitate the ability to take appropriate measures after medical examination of employees. PMID- 26549832 TI - An investigation of a cluster of cervical herniated discs among container truck drivers with occupational exposure to whole-body vibration. AB - OBJECTIVE: This study aimed to determine if occupational exposure to whole-body vibration is associated with cervical intervertebral disc herniation among container truck drivers. METHODS: We conducted a walk-through survey among container truck drivers and unexposed workers. We also measured the vibration hazard of the container truck over the driver's back and seat when the driver was loading a container and driving the loaded truck. RESULTS AND DISCUSSION: Among the 38 workers interviewed, 32 were container truck drivers. Four of them reported cervical herniated discs, and all of these individuals were container truck drivers with a job tenure of greater than 10 years. Self-reported cervical herniated disc, nuchal pain, nocturia, arm/forearm weakness, arm/forearm numbness, and finger numbness were significantly more prevalent as the driver's duration of exposure increased (all p values of test for trend <0.05). The vibration of the truck during and after loading a container was considered the main cause of herniated disc. When a container truck was driven with a loaded container, both the vertical and horizontal vibrating acceleration over the seat and back sites exceeded the 8-hr exposure level based on the ISO 2631-1 criteria. The transient vibration dose values (VDVs) measured during misaligned or unsmooth loading operations were usually greater than the upper bounds of the health guidance caution zone for the 8-hr VDV. CONCLUSIONS: Our investigation disclosed a cluster of cervical intervertebral disc herniation that was associated with the vibration hazard during long-term container truck driving under full load and possibly aggravated by misaligned loading operations. PMID- 26549833 TI - Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers. AB - OBJECTIVES: Even though shift work has been suspected to be a risk factor for cardiovascular disease, little research has been done to determine the logical underlying inflammation mechanisms. This study investigated the association between shift work and circulating total and differential leukocyte counts among Chinese steel workers. METHODS: The subjects were 1,654 line workers in a steel plant, who responded to a cross-sectional survey with a questionnaire on basic attributes, life style, and sleep. All workers in the plant received a periodic health checkup. Total and differential leukocytes counts were also examined in the checkup. RESULTS: Shift workers had higher rates of alcohol use, smoking, poor sleep, poor physical exercise, and obesity than daytime workers. In further analysis, we found that the peripheral total WBC, monocyte, neutrophil, and lymphocyte counts were also greater in shift workers than in daytime workers. When subjects were divided into quartiles according to total WBC, neutrophil, monocyte, and lymphocyte counts, increased leukocyte count was associated with shift work. Using stepwise linear regression analysis, smoking, obesity, and shift work were independently associated with total WBC, monocyte, neutrophil, and lymphocyte counts. CONCLUSIONS: This study indicates that peripheral total and differential leukocyte counts are significantly higher in shift workers, which suggests that shift work may be a risk factor of cardiovascular disease. Applicable intervention strategies are needed for prevention of cardiovascular disease for shift workers. PMID- 26549834 TI - Neonicotinoid concentrations in urine from chronic kidney disease patients in the North Central Region of Sri Lanka. AB - OBJECTIVES: Neonicotinoid insecticides have been widely used around the world since the 1990s. Reports have been made since the 1990s of rice paddy farmers in the North Central Region (NCR) of Sri Lanka suffering from chronic kidney disease with unknown etiology (CKDu). A preliminary evaluation of the exposure of local farmers in the NCR of Sri Lanka to neonicotinoids was performed. METHODS: We analyzed neonicotinoid and neonicotinoid metabolite concentrations in spot urine samples. We selected 40 samples, 10 from farmers with CKDu and 10 from controls from each of two areas, Medawachchiya and Girandurukotte. RESULTS: Imidacloprid and desmethyl-acetamiprid were found at significantly higher concentrations in the control samples (with medians of 51 ng/l and 340 ng/l, respectively) than in the CKDu samples (medians of 15 ng/l and 150 ng/l, respectively) when the results were not adjusted for the creatinine contents. None of the six compounds that were measured in the urine samples were found at significantly higher concentrations in the CKDu samples than in the control samples. None of the neonicotinoid concentrations in the samples analyzed in this study exceeded the concentrations that have been found in samples from the general population of Japan. CONCLUSIONS: Farmers (both with and without CKDu) living in CKDu-endemic areas in the NCR of Sri Lanka are exposed to lower neonicotinoid concentrations than non-occupationally exposed residents of Japan. PMID- 26549835 TI - Underlying spirituality and mental health: the role of burnout. AB - OBJECTIVE: This study investigated the effects of burnout on the relationship between spirituality and mental health among healthcare workers in Hong Kong. METHODS: Using a cross-sectional design, 312 healthcare workers (mean age=38.6, SD=9.9; 77.7% females) in a mental rehabilitation institution completed a self administered questionnaire on anxiety, depression, burnout, and daily spiritual experiences. Multivariate regressions were used to test the effects of burnout on the relationships between daily spiritual experiences and anxiety and depression. RESULTS: After adjusting for age, education level, marital status, and staff ranking, higher levels of daily spiritual experience were associated with lower levels of burnout (beta=-0.22, p<0.01), depression (beta=-0.68, p<0.01), and anxiety (beta=-0.05, p<0.01). Burnout was found to have a significant partial mediating effect on the relationship between daily spiritual experiences and depression (z=-2.99, p<0.01), accounting for 37.8% of the variation in depression. Burnout also completely mediated the relationship between daily spiritual experiences and anxiety (z=-3.06, p<0.01), accounting for 73.9% of the variation in anxiety. CONCLUSIONS: The results suggested that the association between spirituality and mental health is influenced by the level of burnout, thereby supporting the role of burnout as a potential mediator. Moreover, day-to day spiritual practice was found to be potentially protective against burnout and mental health problems. Future interventions could incorporate spirituality training to reduce burnout so as to improve the well-being of healthcare workers. PMID- 26549836 TI - Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers. AB - OBJECTIVES: Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. METHODS: Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 +/- 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. RESULTS: The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. CONCLUSIONS: While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities. PMID- 26549837 TI - Impacts of users' antisocial behaviors in an ophthalmologic emergency department- a qualitative study. AB - BACKGROUND: Health-care workers in emergency departments are frequently exposed to risk of antisocial behavior and violence (ABV) by users. Underreporting of ABV by health-care professionals has been identified. In order to understand this phenomenon, we explored the experience of ABV in 30 health workers in an ophthalmology emergency department in the Rhone-Alpes administrative region of France. METHODS: A grounded theory qualitative approach was followed. Data were collected from field observations, 30 semistructured individual interviews, violence report forms, and 364 patient satisfaction questionnaires. Qualitative thematic content analysis of the interviews was performed with qualitative data analysis software. RESULTS: Third-party antisocial behaviors and violence were an everyday occurrence, with varying levels of seriousness: impoliteness, vulgarity, nonrecognition, insults, verbal threats, and aggressive gestures. Health-care workers adopted various strategies to adapt to such violence: proactive and reactive attitudes and avoidance. Several organizational factors concerning the political and economic context, hospital work organization, and health workers' behavior were identified as potentially contributing to ABV. Excessive waiting times, lack of user information, and understaffing emerged as factors contributing to users' ABV. CONCLUSIONS: Antisocial behaviors by hospital users are underreported by professionals and under-recognized. They appear to be like continuous occupational exposure leading to delayed adverse consequences either on workers' health or motivation. However, violence in hospitals is not the result of only the action of users, and it may be related to work organization and workers' own behaviors. Only a grounded analysis of the causes of violence in the local work context can uncover relevant solutions. PMID- 26549838 TI - Downregulation of delta opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug-resistant human hepatocellular carcinoma cells to 5 FU. AB - delta opioid receptor (DOR) was the first opioid receptor of the G protein coupled receptor family to be cloned. Our previous studies demonstrated that DOR is involved in regulating the development and progression of human hepatocellular carcinoma (HCC), and is involved in the regulation of the processes of invasion and metastasis of HCC cells. However, whether DOR is involved in the development and progression of drug resistance in HCC has not been reported and requires further elucidation. The aim of the present study was to investigate the expression levels of DOR in the drug-resistant HCC BEL-7402/5-fluorouracil (BEL/FU) cell line, and its effects on drug resistance, in order to preliminarily elucidate the effects of DOR in HCC drug resistance. The results of the present study demonstrated that DOR was expressed at high levels in the BEL/FU cells, and the expression levels were higher, compared with those in normal liver cells. When the expression of DOR was silenced, the proliferation of the drug-resistant HCC cells were unaffected. However, when the cells were co-treated with a therapeutic dose of 5-FU, the proliferation rate of the BEL/FU cells was significantly inhibited, a large number of cells underwent apoptosis, cell cycle progression was arrested and changes in the expression levels of drug-resistant proteins were observed. Overall, the expression of DOR was upregulated in the drug-resistant HCC cells, and its functional status was closely associated with drug resistance in HCC. Therefore, DOR may become a recognized target molecule with important roles in the clinical treatment of drug-resistant HCC. PMID- 26549839 TI - Stretchable Random Lasers with Tunable Coherent Loops. AB - Stretchability represents a key feature for the emerging world of realistic applications in areas, including wearable gadgets, health monitors, and robotic skins. Many optical and electronic technologies that can respond to large strain deformations have been developed. Laser plays a very important role in our daily life since it was discovered, which is highly desirable for the development of stretchable devices. Herein, stretchable random lasers with tunable coherent loops are designed, fabricated, and demonstrated. To illustrate our working principle, the stretchable random laser is made possible by transferring unique ZnO nanobrushes on top of polydimethylsiloxane (PDMS) elastomer substrate. Apart from the traditional gain material of ZnO nanorods, ZnO nanobrushes were used as optical gain materials so they can serve as scattering centers and provide the Fabry-Perot cavity to enhance laser action. The stretchable PDMS substrate gives the degree of freedom to mechanically tune the coherent loops of the random laser action by changing the density of ZnO nanobrushes. It is found that the number of laser modes increases with increasing external strain applied on the PDMS substrate due to the enhanced possibility for the formation of coherent loops. The device can be stretched by up to 30% strain and subjected to more than 100 cycles without loss in laser action. The result shows a major advance for the further development of man-made smart stretchable devices. PMID- 26549841 TI - Effective chemiluminogenic systems based on acridinium esters bearing substituents of various electronic and steric properties. AB - A series of 10-methyl-9-(phenoxycarbonyl)acridinium trifluoromethanesulfonates (XAEs), bearing substituents of various characteristics in the lateral benzene ring (2-halogen, 2,6-dihalogen, 2-trifluoromethyl, 2-nitro, 2-methoxy, 3-halogen and 4-halogen) were synthesized with high yields, identified and subjected to a physicochemical and theoretical investigation. The main task of the work was to assess the mechanism and optimal conditions of light emission in various liquid systems based on the above salts in order to evaluate their potential usefulness as chemiluminescence (CL) labels and indicators in ultra-sensitive analyses. Density functional theory (DFT) calculations were performed to investigate the detailed mechanism of the oxidation of 9-substituted 10-methylacridinium cations involved in XAEs by hydrogen peroxide in alkaline media. Three general pathways were drawn, which are termed the "light path" (chemiluminogenic) and there were two "dark paths" (non-chemiluminogenic): hydrolytic and "pseudobase". The CL time profiles, triggered in alkaline solutions containing hydrogen peroxide, enabled us to establish crucial physicochemical parameters, including pseudo-first order kinetic constants of CL decay and relative efficiencies of emission. In order to optimize the systems' luminogenic performance, different bases, such as sodium hydroxide, tetrabutylammonium hydroxide (TBAOH) and 1,8-diazabicyclo[5.4.0]undec 7-ene (DBU), as well as enhancers, such as cationic, zwitterionic and neutral surfactants (cetyltrimethylammonium chloride (CTAC), N,N-dimethyldodecylammonio 1,3-propane sulfonate (DDAPS) and Triton X-100, respectively) were tested. The results revealed the optimal CL systems, which enabled us to obtain substantially higher emissions than typical ones, based on acridinium esters or luminol. The derived parameters, characterizing the potential utility of the acridinium esters, such as stability in aqueous environments and usefulness (the product of emission efficiency and stability at a given pH), enabled us to reveal the best candidates and their practical applications. The post-reaction mixtures, analyzed by means of chromatography (RP-HPLC) and mass spectrometry (ESI-MS), allowed us to verify the occurrence and population of the products that were theoretically predicted, i.e. 10-methyl-9-acridinone (NMAON), 10-methylacridinium-9-carboxylic acid (NMACA) and substituted phenols (RPhOHs). PMID- 26549840 TI - Multiple Intercostal Space Electrocardiogram Allows Accurate Localization of Outflow Tract Ventricular Arrhythmia Origin. AB - BACKGROUND: Multiple intercostal recordings were supposed to get a more comprehensive view of the depolarization vector of the outflow tract ventricular arrhythmia (OT-VA), which may help to identify the OT-VA more accurately. This study was undertaken to develop a more accurate electrocardiogram (ECG) criterion for differentiating between left and right OT-VA origins. METHODS: We studied OT VA with a left bundle branch block pattern and inferior axis QRS morphology in 47 patients with successful catheter ablation in the right ventricular OT (RVOT; n = 37) or aortic coronary cusp (ACC; n = 10). Superior and inferior precordial leads were taken together with the routine 12-lead ECG. The ECG during the OT-VA and during sinus beats were analyzed. Transition ratio, transition zone (TZ) index, R/S amplitude ratio, and R-wave duration ratio were measured in the regular, superior, and inferior precordial leads. RESULTS: The combined TZ index, TZ index inferior was significantly smaller, while the V2 inferior transition ratio was significantly larger for ACC origins than RVOT origins (P < 0.05). The area under the curve for the combined TZ index by a receiver operating characteristic analysis was 0.974, which was significantly larger than other parameters. A cutoff value <=0.25 predicted an ACC origin with 94% sensitivity and 100% specificity. This advantage of the parameter over others also held true for a subanalysis of OT-VAs with a lead V3 precordial transition or TZ index = 0. CONCLUSIONS: The combined TZ index outperformed other ECG criteria to differentiate left from right OT-VA origins. PMID- 26549842 TI - Soil and Rhizosphere Associated Fungi in Gray Mangroves (Avicennia marina) from the Red Sea--A Metagenomic Approach. AB - Covering a quarter of the world's tropical coastlines and being one of the most threatened ecosystems, mangroves are among the major sources of terrestrial organic matter to oceans and harbor a wide microbial diversity. In order to protect, restore, and better understand these ecosystems, researchers have extensively studied their microbiology, yet few surveys have focused on their fungal communities. Our lack of knowledge is even more pronounced for specific fungal populations, such as the ones associated with the rhizosphere. Likewise, the Red Sea gray mangroves (Avicennia marina) remain poorly characterized, and understanding of their fungal communities still relies on cultivation-dependent methods. In this study, we analyzed metagenomic datasets from gray mangrove rhizosphere and bulk soil samples collected in the Red Sea coast, to obtain a snapshot of their fungal communities. Our data indicated that Ascomycota was the dominant phylum (76%-85%), while Basidiomycota was less abundant (14%-24%), yet present in higher numbers than usually reported for such environments. Fungal communities were more stable within the rhizosphere than within the bulk soil, both at class and genus level. This finding is consistent with the intrinsic patchiness in soil sediments and with the selection of specific microbial communities by plant roots. Our study indicates the presence of several species on this mycobiome that were not previously reported as mangrove-associated. In particular, we detected representatives of several commercially-used fungi, e.g., producers of secreted cellulases and anaerobic producers of cellulosomes. These results represent additional insights into the fungal community of the gray mangroves of the Red Sea, and show that they are significantly richer than previously reported. PMID- 26549843 TI - Borane-Catalyzed Reductive alpha-Silylation of Conjugated Esters and Amides Leaving Carbonyl Groups Intact. AB - Described herein is the development of the B(C6F5)3-catalyzed hydrosilylation of alpha,beta-unsaturated esters and amides to afford synthetically valuable alpha silyl carbonyl products. The alpha-silylation occurs chemoselectively, thus leaving the labile carbonyl groups intact. The reaction features a broad scope of both acyclic and cyclic substrates, and the synthetic utility of the obtained alpha-silyl carbonyl products is also demonstrated. Mechanistic studies revealed two operative steps: fast 1,4-hydrosilylation of conjugated carbonyls and then slow silyl group migration of a silyl ether intermediate. PMID- 26549844 TI - Structural Determinants of the Selectivity of 3-Benzyluracil-1-acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10. AB - The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2-(3-(4-chloro-3-nitrobenzyl)-2,4 dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetic acid (JF0048, 3) and 2-(2,4-dioxo-3 (2,3,4,5-tetrabromo-6-methoxybenzyl)-3,4-dihydropyrimidin-1(2H)-yl)acetic acid (JF0049, 4), which selectively target these enzymes. Although 3 and 4 share the 3 benzyluracil-1-acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE-19 cells, whereas 4 stops proliferation in human lung cancer NCI-H460 cells. PMID- 26549845 TI - Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature. AB - Retinal diseases are the leading causes of irreversible visual impairment and blindness in the developed countries. Human retina has limited regenerative power to replace cell loss. Stem cell replacement therapy has been proposed as a viable option. Previously, we have induced human adult periodontal ligament stem cells (PDLSCs) to the retinal lineage. In this study, we modified our induction protocol to direct human adult PDLSCs into retinal ganglion-like cells and determined the microRNA (miRNA) signature of this transdifferentiation process. The differentiated PDLSCs demonstrated the characteristics of functional neurons as they expressed neuronal and retinal ganglion cell markers (ATOH7, POU4F2, beta III tubulin, MAP2, TAU, NEUROD1 and SIX3), formed synapses and showed glutamate induced calcium responses as well as spontaneous electrical activities. The global miRNA expression profiling identified 44 upregulated and 27 downregulated human miRNAs after retinal induction. Gene ontology analysis of the predicted miRNA target genes confirmed the transdifferentiation is closely related to neuronal differentiation processes. Furthermore, the expressions of 2 miRNA targeted candidates, VEGF and PTEN, were significantly upregulated during the induction process. This study identified the transdifferentiation process of human adult stem cells into retinal ganglion-like cells and revealed the involvement of both genetic and miRNA regulatory mechanisms. PMID- 26549846 TI - Sensitive detection of NMR for thin films. AB - NMR can provide valuable information about thin films, but its relatively low sensitivity allows data acquisition only from bulk samples. The sensitivity problem is circumvented by detection schemes with higher sensitivity and/or enhanced polarization. In most of these ingenious techniques, electrons play a central role through hyperfine interactions with the nuclei of interest or the conversion of the spin orientation to an electric charge. The state of the art in NMR is the control of a single nuclear spin state, the complete form of which is one of the ultimate goals of nanotechnology. PMID- 26549847 TI - Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells. AB - Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB MNCs) of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses. PMID- 26549848 TI - Reprogramming of Polycomb-Mediated Gene Silencing in Embryonic Stem Cells by the miR-290 Family and the Methyltransferase Ash1l. AB - Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR(-/-) ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Polycomb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family. PMID- 26549850 TI - Isolation of Human Colon Stem Cells Using Surface Expression of PTK7. AB - Insertion of reporter cassettes into the Lgr5 locus has enabled the characterization of mouse intestinal stem cells (ISCs). However, low cell surface abundance of LGR5 protein and lack of high-affinity anti-LGR5 antibodies represent a roadblock to efficiently isolate human colonic stem cells (hCoSCs). We set out to identify stem cell markers that would allow for purification of hCoSCs. In an unbiased approach, membrane-enriched protein fractions derived from in vitro human colonic organoids were analyzed by quantitative mass spectrometry. Protein tyrosine pseudokinase PTK7 specified a cell population within human colonic organoids characterized by highest self-renewal and re-seeding capacity. Antibodies recognizing the extracellular domain of PTK7 allowed us to isolate and expand hCoSCs directly from patient-derived mucosa samples. Human PTK7+ cells display features of canonical Lgr5+ ISCs and include a fraction of cells that undergo differentiation toward enteroendocrine lineage that resemble crypt label retaining cells (LRCs). PMID- 26549849 TI - A Chemical Biology Study of Human Pluripotent Stem Cells Unveils HSPA8 as a Key Regulator of Pluripotency. AB - Chemical biology methods such as high-throughput screening (HTS) and affinity based target identification can be used to probe biological systems on a biomacromolecule level, providing valuable insights into the molecular mechanisms of those systems. Here, by establishing a human embryonal carcinoma cell-based HTS platform, we screened 171,077 small molecules for regulators of pluripotency and identified a small molecule, Displurigen, that potently disrupts hESC pluripotency by targeting heat shock 70-kDa protein 8 (HSPA8), the constitutively expressed member of the 70-kDa heat shock protein family, as elucidated using affinity-based target identification techniques and confirmed by loss-of-function and gain-of-function assays. We demonstrated that HSPA8 maintains pluripotency by binding to the master pluripotency regulator OCT4 and facilitating its DNA binding activity. PMID- 26549852 TI - Enhanced Psychosocial Support for Caregiver Burden for Patients With Chronic Kidney Failure Choosing Not to Be Treated by Dialysis or Transplantation: A Pilot Randomized Controlled Trial. AB - BACKGROUND: Family caregivers of patients with chronic kidney failure have increased burden, as reflected by their high frequency of physical and mental disturbances. The impact of enhanced psychosocial support to caregivers of patients with chronic kidney failure remains unclear. STUDY DESIGN: Open-label randomized controlled trial. SETTING & PARTICIPANTS: All new patients referred to the renal palliative clinic were screened. Caregivers of patients who met the following criteria were recruited: (1) chronic kidney failure as defined by creatinine clearance < 15 mL/min, (2) opted for conservative management by nephrology team or patient, (3) never treated with dialysis or transplantation, and (4) able to provide informed consent. INTERVENTIONS: Random assignment to treatment with enhanced psychosocial support or standard renal care (control). Enhanced psychosocial support included counseling and psychosocial interventions by an on-site palliative care nurse and designated social worker. Each caregiver was followed up at 2- to 4-week intervals for up to 6 months. OUTCOMES: Zarit Burden Inventory (ZBI) and Hospital Anxiety and Depression Scale (HADS) in caregivers and McGill Quality of Life scores in patients of both groups were compared. RESULTS: 29 pairs of family caregivers/patients with chronic kidney failure were randomly assigned (intervention, n=14; control, n=15). Mean ages of patients and caregivers were 81.6 +/- 5.1 and 59.8 +/- 14.2 (SD) years, respectively. The intervention group showed significantly lower ZBI scores than the control group at 1 and 3 months (22.0 +/- 5.3 vs 31.6 +/- 9.5 and 21.3 +/- 6.6 vs 33.4 +/- 7.2; P=0.006 and P=0.009, respectively). HADS anxiety scores of caregivers who received the intervention were significantly lower than those of controls at 1 and 3 months (7.1 +/- 3.2 vs 10.1 +/- 2.2 and 6.5 +/- 4.5 vs 11.0 +/- 3.1; P=0.01 and P=0.03, respectively). Insignificant reductions in ZBI and HADS scores were found at 6 months. 19 patients died (intervention, n=10; control, n=9) during the study period. LIMITATIONS: The study is limited by a relatively small sample size and short duration. CONCLUSIONS: Enhanced psychosocial support program in patients with chronic kidney failure and caregivers resulted in an early significant reduction in caregiver burden and anxiety. PMID- 26549851 TI - Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes. AB - The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs. PMID- 26549853 TI - ATPergic signalling during seizures and epilepsy. AB - Much progress has been made over the last few decades in the identification of new anti-epileptic drugs (AEDs). However, 30% of epilepsy patients suffer poor seizure control. This underscores the need to identify alternative druggable neurotransmitter systems and drugs with novel mechanisms of action. An emerging concept is that seizure generation involves a complex interplay between neurons and glial cells at the tripartite synapse and neuroinflammation has been proposed as one of the main drivers of epileptogenesis. The ATP-gated purinergic receptor family is expressed throughout the brain and is functional on neurons and glial cells. ATP is released in high amounts into the extracellular space after increased neuronal activity and during chronic inflammation and cell death to act as a neuro- and gliotransmitter. Emerging work shows pharmacological targeting of ATP-gated purinergic P2 receptors can potently modulate seizure generation, inflammatory processes and seizure-induced brain damage. To date, work showing the functional contribution of P2 receptors has been mainly performed in animal models of acute seizures, in particular, by targeting the ionotropic P2X7 receptor subtype. Other ionotropic P2X and metabotropic P2Y receptor family members have also been implicated in pathological processes following seizures such as the P2X4 receptor and the P2Y12 receptor. However, during epilepsy, the characterization of P2 receptors was mostly restricted to the study of expressional changes of the different receptor subtypes. This review summarizes the work to date on ATP-mediated signalling during seizures and the functional impact of targeting the ATP-gated purinergic receptors on seizures and seizure induced pathology. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID- 26549854 TI - Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice. AB - Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder. Several types of treatments have been tested to block or delay the onset of the disease, but none have been completely successful. Diet, lifestyle and natural products are currently the main scientific focuses. Here, we evaluate the effects of oral administration of the monoterpene linalool (25 mg/kg), every 48 h for 3 months, on aged (21-24 months old) mice with a triple transgenic model of AD (3xTg-AD) mice. Linalool-treated 3xTg-AD mice showed improved learning and spatial memory and greater risk assessment behavior during the elevated plus maze. Hippocampi and amygdalae from linalool-treated 3xTg-AD mice exhibited a significant reduction in extracellular beta-amyloidosis, tauopathy, astrogliosis and microgliosis as well as a significant reduction in the levels of the pro inflammatory markers p38 MAPK, NOS2, COX2 and IL-1beta. Together, our findings suggest that linalool reverses the histopathological hallmarks of AD and restores cognitive and emotional functions via an anti-inflammatory effect. Thus, linalool may be an AD prevention candidate for preclinical studies. PMID- 26549856 TI - Breathing a little bit easier .... PMID- 26549855 TI - A potential prognostic long non-coding RNA signature to predict metastasis-free survival of breast cancer patients. AB - Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes, and dysregulated lncRNAs have demonstrated potential roles as biomarkers and therapeutic targets for cancer prognosis and treatment. In this study, by repurposing microarray probes, we analyzed lncRNA expression profiles of 916 breast cancer patients from the Gene Expression Omnibus (GEO). Nine lncRNAs were identified to be significantly associated with metastasis-free survival (MFS) in the training dataset of 254 patients using the Cox proportional hazards regression model. These nine lncRNAs were then combined to form a single prognostic signature for predicting metastatic risk in breast cancer patients that was able to classify patients in the training dataset into high- and low risk subgroups with significantly different MFSs (median 2.4 years versus 3.0 years, log-rank test p < 0.001). This nine-lncRNA signature was similarly effective for prognosis in a testing dataset and two independent datasets. Further analysis showed that the predictive ability of the signature was independent of clinical variables, including age, ER status, ESR1 status and ERBB2 status. Our results indicated that lncRNA signature could be a useful prognostic marker to predict metastatic risk in breast cancer patients and may improve upon our understanding of the molecular mechanisms underlying breast cancer metastasis. PMID- 26549857 TI - Arm flexion during ultrasound assists localization of an intramuscular etonogestrel contraceptive implant. AB - A nonpalpable etonogestrel implant was identified by high-frequency ultrasound in the biceps muscle 4-6mm below the skin. Active elbow flexion resulted in proximal movement of the implant relative to the ultrasound probe, suggesting localization in the muscle. This maneuver may assist in verifying intramuscular placement prior to surgical excision. PMID- 26549858 TI - tRNA--the golden standard in molecular biology. AB - Transfer RNAs (tRNAs) represent a major class of RNA molecules. Their primary function is to help decode a messenger RNA (mRNA) sequence in order to synthesize protein and thus ensures the precise translation of genetic information that is imprinted in DNA. The discovery of tRNA in the late 1950's provided critical insight into a genetic machinery when little was known about the central dogma of molecular biology. In 1965, Robert Holley determined the first nucleotide sequence of alanine transfer RNA (tRNA(Ala)) which earned him the 1968 Nobel Prize in Physiology or Medicine. Today, tRNA is one of the best described and characterized biological molecules. Here we review some of the key historical events in tRNA research which led to breakthrough discoveries and new developments in molecular biology. PMID- 26549860 TI - Multi-walled carbon nanotubes as solid-phase extraction sorbents for simultaneous determination of type A trichothecenes in maize, wheat and rice by ultra-high performance liquid chromatography-tandem mass spectrometry. AB - A solid-phase extraction (SPE) procedure using multi-walled carbon nanotubes (MWCNTs) as sorbents coupled with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed for simultaneous determination of four type A trichothecenes in maize, wheat and rice for the first time. Several key parameters including the composition of sample loading solutions, washing and elution solvents were thoroughly investigated to achieve optimal SPE recoveries and efficiency. Performance of the MWCNTs materials was significantly affected by pH, and after optimization, n-hexane and 5% methanol aqueous solution as the washing solutions and methanol containing 1% formic acid as the elution solvent presented an excellent purification efficiency for the four targets in the different matrices. The method was validated by determining the linearity (R(2)>=0.992), recovery (73.4-113.7%), precision (1.2-17.1%) and sensitivity (limit of quantification in the range of 0.02-0.10MUg/kg), and was further applied for simultaneous determination of type A trichothecenes in 30 samples. Although low contamination levels of type A trichothecenes in wheat, maize and rice were observed revealing mitigated risks to consumers in Shanghai, China, the developed method has proven to be a valuable tool for type A trichothecenes monitoring in complex crop matrices. PMID- 26549861 TI - Relationships between rabbit semen characteristics and fertilising ability after insemination. AB - This study aimed to analyse the relationship between rabbit semen characteristics and semen fertilising ability after insemination, which is generally found to be weak. Our hypothesis was that using high semen dilutions (1 : 19), non-oestrus stimulated does, and homospermic inseminations would make it easier to predict semen fertilising ability. Semen characteristics were evaluated on 275 ejaculates of 128 INRA1001 bucks, distributed into five successive batches. A total of 1970 inseminations were performed. The continuous semen variables were subdivided into three classes of similar size to account for any non-linear relationship between semen characteristics and fertilising ability. Mass motility was divided into two classes according to the presence or absence of waves under microscope observation. Libido, the presence or absence of gel, volume, percentage of progressive sperms, curvilinear velocity, beat frequency of the flagellum, and straightness and linearity of sperm movement did not affect fertility, prolificacy or productivity. It was confirmed that mass motility, estimated by visual observation under the microscope, significantly influenced fertility as well as the percentage of motile and of rapid sperms, and the amplitude of lateral head displacement, estimated by a computer-assisted semen analysis system. To a lesser extent, the percentage of motile cells and of rapid cells significantly influenced prolificacy. Consequently, mass motility and the percentage of motile cells significantly influenced rabbit doe productivity (+1 live births/AI when the semen showed at least a beginning of wave movement, or when the percentage of motile cells was >84%). Interestingly, a gain of 1.5 rabbits was observed when the percentage of rapid cells changed from 64% to 79%, whereas productivity significantly dropped beyond 83% of rapid cells, reflecting a non-linear relationship. PMID- 26549859 TI - Whole genome re-sequencing of date palms yields insights into diversification of a fruit tree crop. AB - Date palms (Phoenix dactylifera) are the most significant perennial crop in arid regions of the Middle East and North Africa. Here, we present a comprehensive catalogue of approximately seven million single nucleotide polymorphisms in date palms based on whole genome re-sequencing of a collection of 62 cultivars. Population structure analysis indicates a major genetic divide between North Africa and the Middle East/South Asian date palms, with evidence of admixture in cultivars from Egypt and Sudan. Genome-wide scans for selection suggest at least 56 genomic regions associated with selective sweeps that may underlie geographic adaptation. We report candidate mutations for trait variation, including nonsense polymorphisms and presence/absence variation in gene content in pathways for key agronomic traits. We also identify a copia-like retrotransposon insertion polymorphism in the R2R3 myb-like orthologue of the oil palm virescens gene associated with fruit colour variation. This analysis documents patterns of post domestication diversification and provides a genomic resource for this economically important perennial tree crop. PMID- 26549862 TI - Atrophy of type I and II muscle fibers is reversible in the case of grade >2 fatty degeneration of the supraspinatus muscle: an experimental study in rabbits. AB - BACKGROUND: Although clinical investigations indicate that the limit of reversibility of rotator cuff muscles fibers type I and II atrophy is grade 2 of fatty degeneration (FD) according to the Goutallier computed tomography classification, little is known about the morphometric verification of these findings. METHODS: The supraspinatus tendon was detached from the greater tubercle and the infraspinatus and subscapularis in 12 rabbits, and a 12-week observation period followed. This proved to be sufficient for development of grade >2 FD of the supraspinatus tendon. The tendon was then reinserted. The animals were euthanized 24 weeks after tendon reconstruction. The sections of middle part of supraspinatus were stained for adenosine triphosphatase reaction, and morphometric measurements were taken of type I and II muscle fiber diameters. The contralateral shoulders served as controls. RESULTS: The macroscopic inspection of the supraspinatus tendons revealed complete healing in all cases. No statistically significant differences were found between controls and operated on shoulders for type I (P = .13) and type II (P = .55) muscle fibers. CONCLUSIONS: Atrophy of type I and II muscle fibers in rabbit supraspinatus muscle, characterized by grade >2 fatty degeneration according to the Goutallier computed tomography classification, is reversible after 24 weeks from reattachment of its tendon. A requirement for type I and II muscle fibers hypertrophy is a change in the biomechanical and functional conditions of the muscle after its tendon is reconstructed. PMID- 26549863 TI - Reimplantation surgery in patients with implantable cardioverter defibrillators: A qualitative study. AB - OBJECTIVE: The purpose of this study was to examine the experience of recurrent surgery for patients with implantable cardioverter defibrillators (ICD). BACKGROUND: Device replacement is typically required every 4-7 years due to battery depletion. Furthermore, recurrent surgery may be related to lead malfunction or pocket infection. METHODS: Ethnographic methods were used for data collection with 23 ICD reimplanted recipients, 12 men and 11 women, 26-85 years of age. Data were analyzed using a with-in case and cross-case method. RESULTS: Three major themes were identified: Anticipation regarding implantation with three sub-themes of logistics and social considerations, decisions regarding replacement, and financial considerations. Relinquishing control and somatic changes frame perceptions related to the operative and postoperative periods. CONCLUSIONS: The frequency of ICD reimplantation differentiates it from other surgical interventions. Perceptions varied according to past experiences and present day social, financial, and somatic differences. Recipients are resolved to life-long surgery aided by their trust in health care professionals. PMID- 26549864 TI - Depression, anxiety and stress among patients with dialysis and the association with quality of life. AB - Studies addressing the nature of relationship between psychological symptoms and quality of life among dialysis patients in Malaysia are scarce. Hence, this study is intended to investigate the association between psychological symptoms such as depression, anxiety and stress on the quality of life in dialysis patients. A cross sectional multicentre study was conducted from May to October 2012 at 15 centres that provide haemodialysis and/or peritoneal dialysis. Apart from socio demographic profile data collection, WHOQOL-BREF and DASS21 questionnaires were administered to study subjects. All three psychological symptoms had significant impact on quality of life domains of physical health, psychological health, social impact, perceived environment and overall quality of life. These findings suggest that subjects with symptoms of depression, anxiety and stress had poorer quality of life than those without, highlighting the negative impact of psychological symptoms. PMID- 26549865 TI - A Delphi consensus study on salvage brachytherapy for prostate cancer relapse after radiotherapy, a Uro-GEC study. AB - BACKGROUND AND PURPOSE: Patients treated with low radiotherapy dose or treated at young age are at a risk of developing local relapse. Although data are preliminary, brachytherapy seems an attractive treatment option for recurrent prostate cancer after previous radiotherapy. Therefore, the UroGEC group of the GEC-ESTRO conducted a Delphi study, to explore expert opinion on the management of salvage prostate brachytherapy. MATERIAL AND METHODS: For this study, a series of digital questionnaires were sent, which enabled data collection from an international group of experienced participants. Consensus was defined as 80% agreement for each question. RESULTS: Eighteen experts completed all rounds of the Delphi study. After the final round consensus was reached on 17 out of 38 (45%) questions. Consensus was reached in 52% of questions about patient selection, in 50% of the questions about diagnostic tests and in 22% of the questions on performing salvage prostate brachytherapy. CONCLUSIONS: The group was able to find consensus on less than half of the questions. Most consensus was reached on topics involving patient selection and diagnostic tests, where participants could build on their experience of daily practice. However, the way to perform the salvage treatment is less established and results in more disagreement between participants. PMID- 26549866 TI - Innominate and Axillary Cannulation in Aortic Arch Surgery Provide Similar Neuroprotection. AB - BACKGROUND: Contemporaneous trends in cerebral protection during aortic arch surgery include moderate hypothermia (22 degrees C-28 degrees C) and continuous antegrade cerebral perfusion (ACP). Innominate artery cannulation is a simplified, alternative route for ACP; however, clinical outcomes have yet to be evaluated against the gold standard of axillary cannulation. METHODS: Between 2008 and 2015, 140 consecutive patients underwent hemiarch reconstruction with moderate hypothermia and continuous ACP at 2 institutions. Axillary cannulation was used in 74 patients (31.1% female, 64.8 +/- 12.7 years) and the remaining 66 patients (24.2% female, 60.8 +/- 10.5 years) had direct cannulation of the innominate artery for delivery of ACP. RESULTS: Although there were no statistically significant differences in complications, neurological events were almost twice as frequent in innominate (19.7%) than in axillary (10.8%; P = 0.142) whereas prolonged mechanical ventilation was much more common with axillary (17.6%) vs innominate (7.6%; P = 0.078). There were no mortalities in the axillary group and 1 in the innominate group (0% vs 1.5%; P > 0.471) and no statistically significant differences in any other postoperative complications or hospital length of stay. There was a reduction in total operating room time in the innominate group (axillary 454 +/- 115 minutes, innominate 318 +/- 125 minutes; P < 0.001), and in the matched subgroup analysis of patients who underwent Bentall and hemiarch reconstruction (axillary 456 +/- 109 minutes, innominate 370 +/- 106 minutes; P = 0.003). CONCLUSIONS: Axillary and innominate artery cannulation for ACP during proximal aortic arch reconstructive surgery resulted in similarly excellent neurological outcomes. Innominate artery cannulation might reduce total surgical time. Possible clinically relevant differences in neurological and respiratory complications require assessment in randomized controlled trials. PMID- 26549867 TI - The emerging age of endovascular treatment of acute ischaemic stroke and the role of CT angiography in patient work-up: a guide for the radiologist. AB - Recent trial evidence suggests that for patients suffering large-vessel occlusive stroke, endovascular therapy based on the stent-retriever technique is associated with superior clinical outcomes when compared to intravenous thrombolysis alone. The challenge now is how this service is to be delivered. This may involve both centralisation of services around large cities and development of robust networks to receive patients from district general hospitals situated further afield. Both diagnostic and interventional neuroradiology will need to expand. Furthermore, we suggest that it would be advantageous for radiology departments in those hospitals receiving hyperacute stroke patients to perform computed tomography (CT) angiography in addition to non-contrast CT, which also has implications for service delivery in these units. This could swiftly aid identification of patients who might benefit from thrombectomy and improve decision-making through demonstration of occlusive thrombus and of collateral status. PMID- 26549868 TI - Fluoroscopically guided transforaminal epidural steroid injections at a quaternary-care teaching institution: effect of trainee involvement and patient body mass index on fluoroscopy time and patient dose. AB - AIM: To investigate whether there are differences in fluoroscopy time and patient dose for fluoroscopically guided lumbar transforaminal epidural steroid injections (TFESIs) performed by staff radiologists versus with trainees and to evaluate the effect of patient body mass index (BMI) on fluoroscopy time and patient dose, including their interactions with other variables. MATERIALS AND METHODS: Single-level lumbar TFESIs (n=1844) between 1 January 2011 and 31 December 2013 were reviewed. Fluoroscopy time, reference point air kerma (Ka,r), and kerma area product (KAP) were recorded. BMI and trainee involvement were examined as predictors of fluoroscopy time, Ka,r, and KAP in models adjusted for age and gender in multivariable linear models. Stratified models of BMI groups by trainee presence were performed. RESULTS: Increased age was the only significant predictor of increased fluoroscopy time (p<0.0001). Ka,r and KAP were significantly higher in patients with a higher BMI (p<0.0001 and p=0.0009). When stratified by BMI, longer fluoroscopy time predicted increased Ka,r and KAP in all groups (p<0.0001). Trainee involvement was not a statistically significant predictor of fluoroscopy time or Ka,r in any BMI category. KAP was lower with trainees in the overweight group (p=0.0009) and higher in male patients for all BMI categories (p<0.02). CONCLUSION: Trainee involvement did not result in increased fluoroscopy time or patient dose. BMI did not affect fluoroscopy time; however, overweight and obese patients received significantly higher Ka,r and KAP. Male patients received a higher KAP in all BMI categories. Limiting fluoroscopy time and good collimation practices should be reinforced in these patients. PMID- 26549869 TI - Do split sleep/wake schedules reduce or increase sleepiness for continuous operations? AB - This study compared the impact of split and consolidated sleep/wake schedules on subjective sleepiness during the biological day and biological night. This was achieved using a between-group design involving two forced desynchrony protocols: consolidated sleep/wake and split sleep/wake. Both protocols included 7*28-h days with 9.33h in bed and 18.67h of wake each day. While the consolidated sleep/wake protocol had 1*9.33-h sleep opportunity and 1*18.67-h wake period each day, the split sleep/wake protocol had 2*4.67-h sleep opportunities and 2*9.33-h wake periods each day. For both protocols, subjective sleepiness was measured using the Karolinska Sleepiness Scale every 2.5h during wake. A total of 29 healthy adult males participated, with 13 in the consolidated sleep/wake group (mean age=22.5 yrs) and 16 in the split sleep/wake group (mean age=22.6 yrs). On average, subjective sleepiness during wake periods of the split condition was significantly higher than that during the first half of wake periods of the consolidated condition, but was similar to the level during the second half. These findings were observed for wake periods that occurred during both the biological day and biological night. Previous data have shown that cognitive impairment at night is lower for split schedules than consolidated schedules, but the current data indicate that feelings of sleepiness are greater for split schedules than consolidated schedules for at least half of the time awake. Thus, it should be explained to people operating split sleep/wake schedules that although they may perform well, they are likely to feel sleepy. PMID- 26549870 TI - Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. AB - Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 8-10million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity. PMID- 26549871 TI - [A social-health care coordination reference in the fields of mental health and child abuse]. AB - The intervention in families with children at risk of abuse stays as a clear example of the need for intersectional coordination mechanisms within the socio health care framework. Different health services (such as primary care, paediatrics, mental health, community and social services, family support teams and schools) create a network in order to link their main goals in the interest of ensuring children's welfare and improving families situation. This essay aims at describing a performance based on the mentioned guidelines, even though there is no accepted and widespread protocol in this regard. We start our research with a one parent family with two children. The mother suffers from a mental health disorder and she fails to adhere to treatment. Both the father of the two children and his family took advantage of this situation to discredit the mother's capability of taking care of her children. This perception had a great impact in her self-esteem and therefore in her willingness and strength to recover. Meetings were held to share relevant information about both the family's general situation, the children's quality of life and the mother's health. Based on this information, the main goals were set in each professional field in order to develop the intervention project. This example of intersectional coordination shows the importance of its standardization for the sake of ensuring a comprehensive attention towards situations that involve initially individuals but that ends up affecting the whole family. PMID- 26549872 TI - Concurrent visualization of crossing renal vessels with split-bolus magnetic resonance urography. PMID- 26549873 TI - High success rate with new modified endoscopic treatment for high-grade VUR: A pilot study with preliminary report. AB - PURPOSE: Despite the benefits of the minimally invasive endoscopic treatment for vesicoureteral reflux (VUR) it has a major drawback which is low success rate in high grade VUR. For overcoming this problem, we introduce a new modified technique of endoscopic treatment called periureteral injection technique (PIT). MATERIALS AND METHODS: In a prospective study a total of 37 ureters in 19 boys and 14 girls were treated, including 3 bilateral cases. Of 37 units, 30 (81.1%) had grade IV and 7 (18.9%) had grade V primary VUR (18 right, 13 left and 3 bilateral units). Subureteral injection of Vantris((r)) was done at the 5-o'clock and 7-o'clock positions in which the direction of injecting needles were almost parallel. Pre- and post-operative evaluation included urinalysis, urinary tract ultrasonography, voiding cystourethrography (VCUG), dimercaptosuccinic acid scan and urodynamic studies. RESULTS: The median age was 38 months (range 8-125). At 6 months follow up period confirmed with VCUG, the VUR has been disappeared in 34 (91.8%) units and 3 units [2 (5.4%) grade II and 1 (2.7%) had grade III)] had downgraded VUR. Complications included early fever due to urinary tract infection in 1 children, transient dysuria in 2 patients and low back pain in one patient (Summary Table). CONCLUSION: The success rate of PIT for treatment of high grade VUR is high. However, further studies with more patients and longer follow up periods are needed to draw final conclusion. PMID- 26549874 TI - The structure of Resuscitation promoting factor B from M. tuberculosis reveals unexpected ubiquitin-like domains. AB - BACKGROUND: RpfB is a key factor in resuscitation from dormancy of Mycobacterium tuberculosis. This protein is a cell-wall glycosidase, which cleaves cell-wall peptidoglycan. RpfB is structurally complex and is composed of three types of domains, including a catalytic, a G5 and three DUF348 domains. Structural information is currently limited to a portion of the protein including only the catalytic and G5 domains. To gain insights into the structure and function of all domains we have undertaken structural investigations on a large protein fragment containing all three types of domains that constitute RpfB (RpfB3D). METHODS: The structural features of RpfB3D have been investigated combining x-ray crystallography and biophysical studies. RESULTS AND CONCLUSIONS: The crystal structure of RpfB3D provides the first structural characterization of a DUF348 domain and revealed an unexpected structural relationship with ubiquitin. The crystal structure also provides specific structural features of these domains explaining their frequent association with G5 domains. GENERAL SIGNIFICANCE: Results provided novel insights into the mechanism of peptidoglycan degradation necessary to the resuscitation of M. tuberculosis. Features of the DUF348 domain add structural data to a large set of proteins embedding this domain. Based on its structural similarity to ubiquitin and frequent association to the G5 domain, we propose to name this domain as G5-linked-Ubiquitin-like domain, UBLG5. PMID- 26549875 TI - Circulatory changes associated with the closure of the ductus arteriosus in hatching emu (Dromaius novaehollandiae). AB - In developing avian embryos, the right and left ductus arteriosi (DA) allow for a shunt of systemic venous return away from the lungs to the body and chorioallantoic membrane (CAM). Unlike in mammals where the transition from placental respiration to lung respiration is instantaneous, in birds the transition from embryonic CAM respiration to lung respiration can take over 24h. To understand the physiological consequences of this long transition we examined circulatory changes and DA morphological changes during hatching in the emu (Dromaius novaehollandiae), a primitive ratite bird. By tracking microspheres injected into a CAM vein, we observed no change in DA blood flow between the pre pipped to internally pipped stages. Two hours after external pipping, however, a significant decrease in DA blood flow occurred, evident from a decreased systemic blood flow and subsequent increased lung blood flow. Upon hatching, the right-to left shunt disappeared. These physiological changes in DA blood flow correspond with a large decrease in DA lumen diameter from the pre-pipped stages to Day 1 hatchlings. Upon hatching, the right-to-left shunt disappeared and at the same time apoptosis of smooth muscle cells began remodeling the DA for permanent closure. After the initial smooth muscle contraction, the lumen disappeared as intimal cushioning formed, the internal elastic lamina degenerated, and numerous cells underwent regulated apoptosis. The DA closed rapidly between the initiation of external pipping and hatching, resulting in circulatory patterns similar to the adult. This response is most likely produced by increased DA constriction in response to increased arterial oxygen levels and the initiation of vessel remodeling. PMID- 26549876 TI - A comparative study of the response to repeated chasing stress in Atlantic salmon (Salmo salar L.) parr and post-smolts. AB - When Atlantic salmon parr migrate from fresh water towards the sea, they undergo extensive morphological, neural, physiological and behavioural changes. Such changes have the potential to affect their responsiveness to various environmental factors that impose stress. In this study we compared the stress responses in parr and post-smolt salmon following exposure to repeated chasing stress (RCS) for three weeks. At the end of this period, all fish were challenged with a novel stressor and sampled before (T0) and after 1h (T1). Parr had a higher growth rate than post-smolts. Plasma cortisol declined in the RCS groups within the first week suggesting a rapid habituation/desensitisation of the endocrine stress axis. As a result of the desensitised HPI axis, RCS groups showed a reduced cortisol response when exposed to the novel stressor. In preoptic area (POA) crf mRNA levels were higher in all post-smolt groups compared to parr. 11betahsd2 decreased by RCS and by the novel stressor in post-smolt controls (T1), whereas no effect of either stress was seen in parr. The grs were low in all groups except for parr controls. In pituitary, parr controls had higher levels of crf1r mRNA than the other parr and post-smolt groups, whilst pomcb was higher in post-smolt control groups. Overall, 11betahsd2 transcript abundance in parr was lower than post-smolt groups; after the novel stressor pomcs, grs and mr were up-regulated in parr control (T1). In summary, we highlight differences in the central stress response between parr and post-smolt salmon following RCS. PMID- 26549878 TI - Peroxyl radical reactions with carotenoids in microemulsions: Influence of microemulsion composition and the nature of peroxyl radical precursor. AB - The reactions of acetylperoxyl radicals with different carotenoids (7,7'-dihydro beta-carotene and zeta-carotene) in SDS and CTAC microemulsions of different compositions were investigated using laser flash photolysis (LFP) coupled with kinetic absorption spectroscopy. The primary objective of this study was to explore the influence of microemulsion composition and the type of surfactant used on the yields and kinetics of various transients formed from the reaction of acetylperoxyl radicals with carotenoids. Also, the influence of the site (hydrocarbon phases or aqueous phase) of generation of the peroxyl radical precursor was examined by using 4-acetyl-4-phenylpiperidine hydrochloride (APPHCl) and 1,1-diphenylacetone (11DPA) as water-soluble and lipid-soluble peroxyl radical precursors, respectively. LFP of peroxyl radical precursors with 7,7'-dihydro-beta-carotene (77DH) in different microemulsions gives rise to the formation of three distinct transients namely addition radical (lambdamax=460 nm), near infrared transient1 (NIR, lambdamax=700 nm) and 7,7'-dihydro-beta carotene radical cation (77DH(*+), lambdamax=770 nm). In addition, for zeta carotene (ZETA) two transients (near infrared transient1 (NIR1, lambdamax=660 nm) and zeta-carotene radical cation (ZETA(*+), lambdamax=730-740 nm)) are generated following LFP of peroxyl radical precursors in the presence of zeta-carotene (ZETA) in different microemulsions. The results show that the composition of the microemulsion strongly influences the observed yield and kinetics of the transients formed from the reactions of peroxyl radicals (acetylperoxyl radicals) with carotenoids (77DH and ZETA). Also, the type of surfactant used in the microemulsions influences the yield of the transients formed. The dependence of the transient yields and kinetics on microemulsion composition (or the type of surfactant used in the microemulsion) can be attributed to the change of the polarity of the microenvironment of the carotenoid. Furthermore, the nature of the peroxyl radical precursor used (water-soluble or lipid-soluble peroxyl radical precursors) has little influence on the yields and kinetics of the transients formed from the reaction of peroxyl radicals with carotenoids. In the context of the interest in carotenoids as radical scavenging antioxidants, the fates of the addition radicals (formed from the reaction of carotenoid with peroxyl radicals) and carotenoid radical cations are discussed. PMID- 26549879 TI - Consensus for defining and reporting complications after esophagectomy: an important new step in place for using the same language. PMID- 26549877 TI - Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a. AB - Nrf2 regulates the expression of numerous anti-oxidant, anti-inflammatory, and metabolic genes. We observed that, paradoxically, Nrf2 protein levels decline in the livers of aged rats despite the inflammatory environment evident in that organ. To examine the cause(s) of this loss, we investigated the age-related changes in Nrf2 protein homeostasis and activation in cultured hepatocytes from young (4-6 months) and old (24-28 months) Fischer 344 rats. While no age dependent change in Nrf2 mRNA levels was observed (p>0.05), Nrf2 protein content, and the basal and anetholetrithione (A3T)-induced expression of Nrf2-dependent genes were attenuated with age. Conversely, overexpression of Nrf2 in cells from old animals reinstated gene induction. Treatment with A3T, along with bortezomib to inhibit degradation of existing protein, caused Nrf2 to accumulate significantly in cells from young animals (p<0.05), but not old, indicating a lack of new Nrf2 synthesis. We hypothesized that the loss of Nrf2 protein synthesis with age may partly stem from an age-related increase in microRNA inhibition of Nrf2 translation. Microarray analysis revealed that six microRNAs significantly increase >2-fold with age (p<0.05). One of these, miRNA-146a, is predicted to bind Nrf2 mRNA. Transfection of hepatocytes from young rats with a miRNA-146a mimic caused a 55% attenuation of Nrf2 translation that paralleled the age-related loss of Nrf2. Overall, these results provide novel insights for the age-related decline in Nrf2 and identify new targets to maintain Nrf2-dependent detoxification with age. PMID- 26549880 TI - Effects of tertiapin-Q and ZD7288 on changes in sinoatrial pacemaker rhythm during vagal stimulation. AB - Heart rate slowing produced by cardiac parasympathetic (vagal) stimulation is thought to be the result of modulation of the acetylcholine-activated K(+) current (IK,ACh) and the pacemaker current (If) in sinoatrial (SAN) pacemaker cells. However, the contribution of these and other ion currents to vagal slowing is controversial. Here, we examined the contributions of IK,ACh and If to vagal slowing in 15 isolated, vagal-innervated preparations of guinea-pig atria, using 300 nM tertiapin-Q (TQ) and 2 MUM ZD7288 to obtain full and substantial block of these currents, respectively. Blocking IK,ACh alone reduced atrial rate responses to 10-s trains of regular vagal stimulation (supramaximal stimulation, 2-ms duration, 1-10 Hz) by ~50% (P<0.01; N=11); blocking If alone had no effect (N=7). Blocking both IK,ACh and If produced ~90% reduction (P<0.01; N=4). Atrial cycle length response to a single burst of vagal stimuli (3 stimuli at 50 Hz), delivered at the optimum phase of the cycle was strongly suppressed by blocking IK,ACh (reduced by 98%; P<0.01; N=9), and modestly reduced by blocking If alone (by ~43%; P=0.20; N=6). The response was abolished by combined block of IK,ACh and If (P=0.04; N=4). Our data show that modulation of IK,ACh and If is sufficient to account for all the vagal slowing observed in this preparation. The vagally-induced negative shift in activation potential for If will be opposed by hyperpolarisation of SAN through activation of IK,ACh. Thus removal of IK,ACh by TQ may have exaggerated the overall contribution of If to vagal slowing. PMID- 26549881 TI - Ineffective VTA Disinhibition in Protracted Opiate Withdrawal. AB - Recently, Kaufling and Aston-Jones showed that, under protracted opiate withdrawal, control of dopamine activity by the tail of the ventral tegmental area shifts from a bidirectional influence towards one-way inhibition. Beyond dysphoric states accompanying withdrawal, these results may also impact research on depression and individual differences in coping and affect. PMID- 26549883 TI - Long-Range Attention Networks: Circuit Motifs Underlying Endogenously Controlled Stimulus Selection. AB - Attention networks comprise brain areas whose coordinated activity implements stimulus selection. This selection is reflected in spatially referenced priority maps across frontal-parietal-collicular areas and is controlled through interactions with circuits representing behavioral goals, including prefrontal, cingulate, and striatal circuits, among others. We review how these goal providing structures control stimulus selection through long-range dynamic projection motifs. These motifs (i) combine feature-tuned subnetworks to a distributed priority map, (ii) establish endogenously controlled, long-range coherent activity at 4-10 Hz theta and 12-30 Hz beta-band frequencies, and (iii) are composed of unique cell types implementing long-range networks through disynaptic disinhibition, dendritic gating, and feedforward inhibitory gain control. This evidence reveals common circuit motifs used to coordinate attentionally selected information across multi-node brain networks during goal directed behavior. PMID- 26549882 TI - Innate Immunity Fights Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most common age-related dementia. Pathognomonic accumulation of cerebral beta-amyloid plaques likely results from imbalanced production and removal of amyloid-beta (Abeta) peptides. In AD, innate immune cells lose their ability to restrict cerebral Abeta accumulation. At least in principle, mononuclear phagocytes can be enlisted to clear Abeta/beta-amyloid from the brain. While the classical focus has been on dampening neuroinflammation in the context of AD, we hypothesize that rebalancing cerebral innate immunity by inhibiting actions of key anti-inflammatory cytokines returns the brain to a physiological state. Recent experiments demonstrating beneficial effects of blocking anti-inflammatory cytokine signaling in preclinical mouse models provide supportive evidence. This concept represents an important step toward innate immune-targeted therapy to combat AD. PMID- 26549884 TI - Neuropeptide Y: An Anti-Aging Player? AB - Accumulating evidence suggests that neuropeptide Y (NPY) has a role in aging and lifespan determination. In this review, we critically discuss age-related changes in NPY levels in the brain, together with recent findings concerning the contribution of NPY to, and impact on, six hallmarks of aging, specifically: loss of proteostasis, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing, cellular senescence, and mitochondrial dysfunction. Understanding how NPY contributes to, and counteracts, these hallmarks of aging will open new avenues of research on limiting damage related to aging. PMID- 26549885 TI - New Mendelian Disorders of Painlessness. AB - Erroneous activation of the pain-sensing system, as in chronic or neuropathic pain, represents a major health burden with insufficient treatment options. However, the study of genetic disorders rendering individuals completely unable to feel pain offers hope. All causes of congenital painlessness affect nociceptors, evolutionarily conserved specialist neurons able to sense all type of tissue damage. The discovery of new genes essential for sensing pain (SCN11A, PRDM12, and CLTCL1) has provided unexpected insights into the biological mechanisms that drive distinct stages of nociception. Drugs targeting two previously discovered painlessness genes, NGF and SCN9A, are currently in late stage clinical trials; thus, characterization of these new painlessness genes has significant potential for the generation of new classes of analgesics. PMID- 26549886 TI - Neural Cross-Frequency Coupling: Connecting Architectures, Mechanisms, and Functions. AB - Neural oscillations are ubiquitously observed in the mammalian brain, but it has proven difficult to tie oscillatory patterns to specific cognitive operations. Notably, the coupling between neural oscillations at different timescales has recently received much attention, both from experimentalists and theoreticians. We review the mechanisms underlying various forms of this cross-frequency coupling. We show that different types of neural oscillators and cross-frequency interactions yield distinct signatures in neural dynamics. Finally, we associate these mechanisms with several putative functions of cross-frequency coupling, including neural representations of multiple environmental items, communication over distant areas, internal clocking of neural processes, and modulation of neural processing based on temporal predictions. PMID- 26549887 TI - Scattering attributes of one-dimensional semiconducting oxide nanomaterials individually probed for varying light-matter interaction angles. AB - We report the characteristic optical responses of one-dimensional semiconducting oxide nanomaterials by examining the individual nanorods (NRs) of ZnO, SnO2, indium tin oxide, and zinc tin oxide under precisely controlled, light-matter interaction geometry. Scattering signals from a large set of NRs of the different types are evaluated spatially along the NR length while varying the NR tilt angle, incident light polarization, and analyzer rotation. Subsequently, we identify material-indiscriminate, NR tilt angle- and incident polarization dependent scattering behaviors exhibiting continuous, intermittent, and discrete responses. The insight gained from this study can advance our fundamental understanding of the optical behaviors of the technologically useful nanomaterials and, at the same time, promote the development of highly miniaturized, photonic and bio-optical devices utilizing the spatially controllable, optical responses of the individual semiconducting oxide NRs. PMID- 26549888 TI - Improving z-tracking accuracy in the two-photon single-particle tracking microscope. AB - Here, we present a method that can improve the z-tracking accuracy of the recently invented TSUNAMI (Tracking of Single particles Using Nonlinear And Multiplexed Illumination) microscope. This method utilizes a maximum likelihood estimator (MLE) to determine the particle's 3D position that maximizes the likelihood of the observed time-correlated photon count distribution. Our Monte Carlo simulations show that the MLE-based tracking scheme can improve the z tracking accuracy of TSUNAMI microscope by 1.7 fold. In addition, MLE is also found to reduce the temporal correlation of the z-tracking error. Taking advantage of the smaller and less temporally correlated z-tracking error, we have precisely recovered the hybridization-melting kinetics of a DNA model system from thousands of short single-particle trajectories in silico. Our method can be generally applied to other 3D single-particle tracking techniques. PMID- 26549889 TI - Influence of humic substances on electrochemical degradation of trichloroethylene in limestone aquifers. AB - In this study we investigate the influence of humic substances (HS) on electrochemical transformation of trichloroethylene (TCE) in groundwater from limestone aquifers. A laboratory flow-through column with an electrochemical reactor that consists of a palladized iron foam cathode followed by a MMO anode was used to induce TCE electro-reduction in groundwater. Up to 82.9% TCE removal was achieved in the absence of HS. Presence of 1, 2, 5, and 10 mgTOC L-1 reduced TCE removal to 70.9%, 61.4%, 51.8% and 19.5%, respectively. The inverse correlation between HS content and TCE removal was linear. Total organic carbon (TOC), dissolved organic carbon (DOC) and absorption properties (A=254 nm, 365 nm and 436 nm) normalized to DOC, were monitored during treatment to understand the behavior and impacts of HS under electrochemical processes. Changes in all parameters occurred mainly after contact with the cathode, which implies that the HS are reacting either directly with electrons from the cathode or with H2 formed at the cathode surface. Since hydrodechlorination is the primary TCE reduction mechanism in this setup, reactions of the HS with the cathode limit transformation of TCE. The presence of limestone gravel reduced the impact of HS on TCE removal. The study concludes that presence of humic substances adversely affects TCE removal from contaminated groundwater by electrochemical reduction using palladized cathodes. PMID- 26549890 TI - Predicting the Academic Achievement of Deaf and Hard-of-Hearing Students From Individual, Household, Communication, and Educational Factors. AB - Research suggests that the academic achievement of deaf and hard-of-hearing (DHH) students is the result of a complex interplay of many factors. These factors include characteristics of the students (e.g., hearing thresholds, language fluencies, mode of communication, and communication functioning), characteristics of their family environments (e.g., parent education level, socioeconomic status), and experiences inside and outside school (e.g., school placement, having been retained at grade level). This paper examines the relative importance of such characteristics to U.S. DHH secondary students' academic achievement as indicated by the Woodcock-Johnson III subtests in passage comprehension, mathematics calculation, science, and social studies. Data were obtained for approximately 500 DHH secondary students who had attended regular secondary schools or state-sponsored special schools designed for DHH students. Across all subject areas, having attended regular secondary schools and having better spoken language were associated with higher test scores. Significant negative predictors of achievement varied by type of subtest but included having an additional diagnosis of a learning disability, having a mild hearing loss, and being African American or Hispanic. The findings have important implications for policy and practice in educating DHH students as well for interpreting previous research. PMID- 26549891 TI - The Design and Operation of Ultra-Sensitive and Tunable Radio-Frequency Interferometers. AB - Dielectric spectroscopy (DS) is an important technique for scientific and technological investigations in various areas. DS sensitivity and operating frequency ranges are critical for many applications, including lab-on-chip development where sample volumes are small with a wide range of dynamic processes to probe. In this work, we present the design and operation considerations of radio-frequency (RF) interferometers that are based on power-dividers (PDs) and quadrature-hybrids (QHs). Such interferometers are proposed to address the sensitivity and frequency tuning challenges of current DS techniques. Verified algorithms together with mathematical models are presented to quantify material properties from scattering parameters for three common transmission line sensing structures, i.e., coplanar waveguides (CPWs), conductor-backed CPWs, and microstrip lines. A high-sensitivity and stable QH-based interferometer is demonstrated by measuring glucose-water solution at a concentration level that is ten times lower than some recent RF sensors while our sample volume is ~1 nL. Composition analysis of ternary mixture solutions are also demonstrated with a PD based interferometer. Further work is needed to address issues like system automation, model improvement at high frequencies, and interferometer scaling. PMID- 26549892 TI - Does Marriage Moderate Genetic Effects on Delinquency and Violence? AB - Using data from the National Longitudinal Study of Adolescent to Adult Health (N = 1,254), the authors investigated whether marriage can foster desistance from delinquency and violence by moderating genetic effects. In contrast to existing gene-environment research that typically focuses on one or a few genetic polymorphisms, they extended a recently developed mixed linear model to consider the collective influence of 580 single nucleotide polymorphisms in 64 genes related to aggression and risky behavior. The mixed linear model estimates the proportion of variance in the phenotype that is explained by the single nucleotide polymorphisms. The authors found that the proportion of variance in delinquency/violence explained was smaller among married individuals than unmarried individuals. Because selection, confounding, and heterogeneity may bias the estimate of the Gene * Marriage interaction, they conducted a series of analyses to address these issues. The findings suggest that the Gene * Marriage interaction results were not seriously affected by these issues. PMID- 26549893 TI - Food Based Complementary Feeding Strategies for Breastfed Infants: What's the Evidence that it Matters? AB - The period of complementary feeding represents a major portion of the 1000 day critical window and thus impacts a period of substantial and dynamic infant development. This review highlights and synthesizes findings of several recent studies conducted to evaluate food based strategies on outcomes related to micronutrient status, growth and neurocognitive development. Particular emphasis is placed on interventions using meat or fortified products to impact iron and zinc intakes, due to the dependence of breastfed infants on complementary food choices to meet requirements for these two critical micronutrients. Regular consumption of modest amounts of meat or fortified cereals provides adequate absorbed zinc to meet estimated physiologic requirements, whereas homeostatic adaptation to lower zinc intake from unfortified cereal/plant staples is inadequate to meet requirements. Iron fortification of cereals may be somewhat more effective than meat to improve iron status, but neither prevents iron deficiency in breastfed infants, even in westernized settings. Improvements in the quality of complementary foods have had very modest effects on linear growth in settings where stunting is prevalent. Maternal education is strongly associated with both linear growth and with child neurodevelopment. The determinants of early growth faltering are more complex and intractable than 'simple' dietary deficiencies of micronutrients. Solutions to growth faltering in young children most likely need to be multi-factorial, and almost certainly will need to start earlier than the complementary feeding period. PMID- 26549894 TI - The Role of Organ Transplantation in Pediatrics. PMID- 26549895 TI - Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants. AB - A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo. PMID- 26549897 TI - Local innovations and country ownership for sustainable development. PMID- 26549898 TI - Gender, health and the Sustainable Development Goals. PMID- 26549899 TI - Public health round-up. PMID- 26549900 TI - Averting climate change's health effects in Fiji. AB - Pacific islanders face up to the dire health effects of global warming. Atasa Moceituba and Monique Tsang report. PMID- 26549901 TI - Don't wait for Paris summit to improve health. AB - How developing countries will make the transition to sustainable clean-energy economies is a major challenge for the United Nations summit that opens in Paris this month. Christiana Figueres talks to Andreia Azevedo Soares. PMID- 26549902 TI - An insecticide-treated bed-net campaign and childhood malaria in Burkina Faso. AB - OBJECTIVE: To investigate if the first national insecticide-treated bed-net campaign in Burkina Faso, done in 2010, was followed by a decrease in childhood malaria in a district with high baseline transmission of the disease. METHODS: We obtained data on the prevalence of Plasmodium falciparum parasitaemia in children aged 2 weeks to 36 months from malaria surveys in 2009 and 2011. We assessed morbidity in children younger than 5 years by comparing data from the Nouna health district's health management information system before and after the campaign in 2010. We analysed mortality data from 2008 to 2012 from Nouna's health and demographic surveillance system. FINDINGS: The bed-net campaign was associated with an increase in the reported use of insecticide-treated nets. In 2009, 73% (630/869) of children reportedly slept under nets. In 2011, 92% (449/487) did. The campaign had no effect on the proportion of young children with P. falciparum parasitaemia after the rainy season; 52% (442/858) in 2009 and 53% (263/499) in 2011. Cases of malaria increased markedly after the campaign, as did the number of children presenting with other diseases. The campaign was not associated with any changes in child mortality. CONCLUSION: The 2010 insecticide treated net campaign in Burkina Faso was not associated with a decrease in care seeking for malaria or all-cause mortality in children younger than 5 years. The most likely explanation is the high coverage of nets in the study area before the campaign which could have had an effect on mosquito vectors, limiting the campaign's impact. PMID- 26549903 TI - Facility-based active management of the third stage of labour: assessment of quality in six countries in sub-Saharan Africa. AB - OBJECTIVE: To assess the quality of facility-based active management of the third stage of labour in Ethiopia, Kenya, Madagascar, Mozambique, Rwanda and the United Republic of Tanzania. METHODS: Between 2009 and 2012, using a cross-sectional design, 2317 women in 390 health facilities were directly observed during the third stage of labour. Observers recorded the use of uterotonic medicines, controlled cord traction and uterine massage. Facility infrastructure and supplies needed for active management were audited and relevant guidelines reviewed. FINDINGS: Most (94%; 2173) of the women observed were given oxytocin (2043) or another uterotonic (130). The frequencies of controlled cord traction and uterine massage and the timing of uterotonic administration showed considerable between-country variation. Of the women given a uterotonic, 1640 (76%) received it within three minutes of the birth. Uterotonics and related supplies were generally available onsite. Although all of the study countries had national policies and/or guidelines that supported the active management of the third stage of labour, the presence of guidelines in facilities varied across countries and only 377 (36%) of 1037 investigated providers had received relevant training in the previous three years. CONCLUSION: In the study countries, quality and coverage of the active management of the third stage of labour were high. However, to improve active management, there needs to be more research on optimizing the timing of uterotonic administration. Training on the use of new clinical guidelines and implementation research on the best methods to update such training are also needed. PMID- 26549904 TI - Using patient-held records to evaluate contraceptive use in Malawi. AB - OBJECTIVE: To investigate a method of using patient-held records to collect contraception data in Malawi, that could be used to explore contraceptive discontinuation and method switching. METHODS: In 2012, all 7393 women aged 15 to 49 years living in the area covered by the Karonga demographic surveillance site were offered a family planning card, which was attached to the woman's health passport - a patient-held medical record. Health-care providers were trained to use the cards to record details of contraception given to women. During the study, providers underwent refresher training sessions and received motivational text messages to improve data completeness. After one year, the family planning cards were collected for analysis. FINDINGS: Of the 7393 eligible women, 6861 (92.8%) received a family planning card and 4678 (63.3%) returned it after one year. Details of 87.3% (2725/3122) of contacts between health-care providers and the women had been recorded by health-care providers on either family planning cards or health passports. Lower-level health-care providers were more diligent at recording data on the family planning cards than higher-level providers. CONCLUSION: The use of family planning cards was an effective way of recording details of contraception provided by family planning providers. The involvement of health-care providers was key to the success of this approach. Data collected in this way should prove helpful in producing accurate estimates of method switching and the continuity of contraceptive use by women. PMID- 26549905 TI - Cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis in China. AB - OBJECTIVE: To investigate the cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis launched in four sites in China in 2011. METHODS: In 2011-2012, we reviewed the records of 172 patients with drug-resistant tuberculosis who enrolled in the comprehensive programme and we collected relevant administrative data from hospitals and China's public health agency. For comparison, we examined a cohort of 81 patients who were treated for drug resistant tuberculosis in 2006-2009. We performed a cost-effectiveness analysis, from a societal perspective, that included probabilistic uncertainty. We measured early treatment outcomes based on three-month culture results and modelled longer term outcomes to facilitate estimation of the comprehensive programme's cost per disability-adjusted life-year (DALY) averted. FINDINGS: The comprehensive programme cost 8837 United States dollars (US$) per patient treated. Low enrolment rates meant that some fixed costs were higher, per patient, than expected. Although the comprehensive programme appeared 30 times more costly than the previous one, it resulted in greater health benefits. The comprehensive programme, which cost US$ 639 (95% credible interval: 112 to 1322) per DALY averted, satisfied the World Health Organization's criterion for a very cost effective intervention. CONCLUSION: The comprehensive programme, which included rapid screening, standardized care and financial protection, improved individual outcomes for MDR tuberculosis in a cost-effective manner. To support post-2015 global heath targets, the comprehensive programme should be expanded to non residents and other areas of China. PMID- 26549906 TI - Evidence on global medical travel. AB - The potential benefits of travelling across national borders to obtain medical treatment include improved care, decreased costs and reduced waiting times. However, medical travel involves additional risks, compared to obtaining treatment domestically. We review the publicly-available evidence on medical travel. We suggest that medical travel needs to be understood in terms of its potential risks and benefits so that it can be evaluated against alternatives by patients who are seeking care. We propose three domains -quality standards, informed decision-making, economic and legal protection - in which better evidence could support the development of medical travel policies. PMID- 26549907 TI - Tuberculosis control in China: use of modelling to develop targets and policies. AB - It is unclear if current programmes in China can achieve the post-2015 global targets for tuberculosis - 50% reduction in incidence and a 75% reduction in mortality by 2025. Chinese policy-makers need to maintain the recent decline in the prevalence of tuberculosis, while revising control policies to cope with an epidemic of drug-resistant tuberculosis and the effects of ongoing health reform. Health reforms are expected to shift patients from tuberculosis dispensaries to designated hospitals. We developed a mathematical model of tuberculosis control in China to help set appropriate targets and prioritize interventions that might be implemented in the next 10 years. This model indicates that, even under the most optimistic scenario - improved treatment in tuberculosis dispensaries, introduction of a new effective regimen for the treatment of drug-susceptible tuberculosis and optimal care of cases of multidrug-resistant tuberculosis - the current global targets for tuberculosis are unlikely to be reached. However, reductions in the incidence of multidrug-resistant tuberculosis should be feasible. We conclude that a shift of patients from tuberculosis dispensaries to designated hospitals is likely to hamper efforts at tuberculosis control if cure rates in the designated hospitals cannot be maintained at a high level. Our results can inform the planning of tuberculosis control in China. PMID- 26549908 TI - Access to hepatitis C medicines. AB - Hepatitis C is a global epidemic. Worldwide, 185 million people are estimated to be infected, most of whom live in low- and middle-income countries. Recent advances in the development of antiviral drugs have produced therapies that are more effective, safer and better tolerated than existing treatments for the disease. These therapies present an opportunity to curb the epidemic, provided that they are affordable, that generic production of these medicines is scaled up and that awareness and screening programmes are strengthened. Pharmaceutical companies have a central role to play. We examined the marketed products, pipelines and access to medicine strategies of 20 of the world's largest pharmaceutical companies. Six of these companies are developing medicines for hepatitis C: AbbVie, Bristol-Myers Squibb, Gilead, Johnson & Johnson, Merck & Co. and Roche. These companies employ a range of approaches to supporting hepatitis C treatment, including pricing strategies, voluntary licensing, capacity building and drug donations. We give an overview of the engagement of these companies in addressing access to hepatitis C products. We suggest actions companies can take to play a greater role in curbing this epidemic: (i) prioritizing affordability assessments; (ii) developing access strategies early in the product lifecycle; and (iii) licensing to manufacturers of generic medicines. PMID- 26549909 TI - Implementation of information and communication technologies for health in Bangladesh. AB - PROBLEM: Bangladesh has yet to develop a fully integrated health information system infrastructure that is critical to guiding policy development and planning. APPROACH: Initial pilot telemedicine and eHealth programmes were not coordinated at national level. However, in 2011, a national eHealth policy was implemented. LOCAL SETTING: Bangladesh has made substantial improvements to its health system. However, the country still faces public health challenges with limited and inequitable access to health services and lack of adequate resources to meet the demands of the population. RELEVANT CHANGES: In 2008, eHealth services were introduced, including computerization of health facilities at sub district levels, internet connections, internet servers and an mHealth service for communicating with health-care providers. Health facilities at sub-district levels were provided with internet connections and servers. In 482 upazila health complexes and district hospitals, an mHealth service was set-up where an on-duty doctor is available for patients at all hours to provide consultations by mobile phone. A government operated telemedicine service was initiated and by 2014, 43 fully equipped centres were in service. These centres provide medical consultations by qualified physicians to patients visiting rural and remote community clinics and union health centres. LESSONS LEARNT: Despite early pilot interventions and successful implementation, progress in adopting eHealth strategies in Bangladesh has been slow. There is a lack of common standards on information technology for health, which causes difficulties in data management and sharing among different databases. Limited internet bandwidth and the high cost of infrastructure and software development are barriers to adoption of these technologies. PMID- 26549911 TI - The right to water in the slums of Mumbai, India. PMID- 26549910 TI - Exposure to cold weather during a mass gathering in the Philippines. AB - PROBLEM: The visit of Pope Francis to the Philippines in January 2015 coincided with a tropical storm. For security reasons, the only road in and out of the area was closed 14.5 hours before the Pope's arrival. This meant that people had to wait for many hours with little shelter at the site. Medical teams in the field reported high numbers of people with cold stress during the mass gathering. APPROACH: To review the event from a public health perspective, we examined the consultations made by medical teams in the field and interviewed key stakeholders, focusing on cold stress as a public health risk. LOCAL SETTING: The key reason for the Pope's visit to Palo and Tacloban was the devastation caused in these cities by typhoon Haiyan in 2013. We estimated that the visit attracted 300 000 people. The medical teams were advised to consider cold stress risks two days before the event but no other measures were taken. RELEVANT CHANGES: Of the 1051 people seeking medical care, 231 people were experiencing symptoms of cold stress. People with cold stress ranged from 2 to 89 years of age and were more likely to be female than male, 173 (75%) versus 57 (25%). LESSONS LEARNT: Planning for mass gatherings should consider a wide range of public health risks, including cold stress. Improved data collection from the field is necessary to maximize the benefits of post-event evaluations and improve public health preparedness. Security measures to ensure the safety of key figures must be balanced with public health risks. PMID- 26549912 TI - Influence of Oil Contamination on Physical and Biological Properties of Forest Soil After Chainsaw Use. AB - Forestry works using chainsaws result in up to 7 million liters of various mineral oils being soaked annually into forest soils. These substances, containing a complex mixture of polycyclic aromatic hydrocarbons (PAHs), are highly toxic. The aim of the study was to determine the effect of oil contamination with PAHs on the physical and biological properties of forest soils. The study area was located in southern Poland in the Miechow forest district. The experiment was conducted on four treatment blocks with various amounts of oil addition. The study included the determination of PAH content, dehydrogenase and urease activity, and biomass of earthworms. Physical properties were determined using the dryer method and Kopecky rings of 250 cm3 volume. The results obtained confirmed the hypothesis that oil contamination with PAHs modified the physical properties of forest soils and oil had a negative impact on enzyme activity in soil. Enzyme activity in the studied soils was negatively correlated with PAH content. Earthworm population density reflected the contamination level of oil-contaminated soils. PMID- 26549914 TI - Social Anthropology and Social Science History. AB - In the 1970s, when the social science history movement emerged in the United States, leading to the founding of the Social Science History Association, a simultaneous movement arose in which historians looked to cultural anthropology for inspiration. Although both movements involved historians turning to social sciences for theory and method, they reflected very different views of the nature of the historical enterprise. Cultural anthropology, most notably as preached by Clifford Geertz, became a means by which historians could find a theoretical basis in the social sciences for rejecting a scientific paradigm. This article examines this development while also exploring the complex ways cultural anthropology has embraced-and shunned-history in recent years. PMID- 26549913 TI - Can Visual Field Progression be Predicted by Confocal Scanning Laser Ophthalmoscopic Imaging of the Optic Nerve Head in Glaucoma? (An American Ophthalmological Society Thesis). AB - PURPOSE: To determine whether confocal scanning laser ophthalmoscopic imaging (Heidelberg retinal tomography [HRT]) can predict visual field change in glaucoma. METHODS: The study included 561 patients with glaucoma or ocular hypertension whose clinical course was followed at the Mount Sinai Faculty practice. Humphrey visual fields (HVFs) and HRT images were collected on one randomly selected eye per patient. Glaucoma progression was determined by the presence of two sequential statistically significant negative slopes in mean deviation (MD) or visual field index (VFI) at any point during the study period. Trend-based analysis on HRT parameters was used to determine progressive changes and whether these occurred before or after HVF change. Sensitivity and specificity of HRT to predict HVF change were calculated. HVF rate of change was correlated to the rate of change detected by HRT imaging. RESULTS: Approximately 17% of patients progressed by either MD or VFI criteria. MD and VFI correlated highly and identified overlapping sets of patients as progressing. HRT global parameters had poor sensitivity (~42%) and moderate specificity (~67%) to predict HVF progression. Regional stereometric parameters were more sensitive (69%-78%) but significantly less specific (24%-27%). Sensitivity of global stereometric parameters in detecting HVF change was not significantly affected by the level of visual field damage (P=.3, Fisher exact test). HVF rate of change did not correlate with rate of change of HRT parameters. CONCLUSIONS: Trend-based analysis of HRT parameters has poor sensitivity and specificity in predicting HVF change. This may be related specifically to HRT imaging or may reflect the fact that in some patients with glaucoma, functional changes precede structural alterations. PMID- 26549915 TI - CONDYLAR RESORPTION IN PATIENTS WITH TMD. AB - The objective of this study is to determine the nature of the difference between condyle morphology of osteoarthritic temporomandibular joint (TMJ) and non osteoarthritic TMJ, using 3D surface models constructed from cone-beam CT (CBCT) images. Three-dimensional Shape Correspondence was used to localize and quantify condylar morphological differences of 20 patients with RDC/TMD group III (arthralgia, arthritis, arthrosis) compared to 40 asymptomatic subjects. Three dimensional models of right and left condyles for each subject were constructed from CBCT images and shape analysis performed using the publicly available SPHARM PDM software. The right and left condyles were normalized using rigid Procrustes alignment to an overall mean condylar surface per group. The mean differences between groups were compared using the Hotelling T2 analysis with permutation test derived p-values, corrected for False Discovery Rate. The differences between the group mean surfaces were visualized with color-coded magnitude and difference vectors. The condylar morphology of the TMD group was statistically significantly different from the asymptomatic group (p = 0.05, average surface distance differences of 1.9 mm for the right condyles and 2.3 mm for the left condyles). The average condylar morphology in the TMD patients showed resorption of the anterior surface of the lateral pole and flattening of the articular surface compared to the mean morphology in asymptomatic subjects. The condylar morphology and condylar dimensions of the TMD patients were different, on average, from those of the asymptomatic subjects. The preliminary findings in this cross-sectional study will lead to future investigations to elucidate osteoarthritic changes in TMD and their role in the pathophysiology of TMD. Supported by NIDCR DE017727. PMID- 26549916 TI - Tractional Forces, Work and Energy Densities in the Human TMJ. AB - The role of mechanics in degenerative joint disease of the temporomandibular joint (TMJ) is largely unknown. Objectives were to: 1) develop an empirical model to relate variables of cartilage mechanics and tractional forces; and 2) use the empirical model to estimate tractional forces for calculations of work done (mJ) and energy densities (mJ/mm3) in living human TMJs. Sixty-four porcine discs were statically, then dynamically loaded. Aspect ratios and velocities of stress fields, compressive strains, and tractional forces were recorded and fit to a quadratic equation to derive the empirical model. Aspect ratios and velocities of stress-fields and cartilage thicknesses then were measured via dynamic stereometry in 15 humans with healthy TMJs and 11 with TMJ disc displacement. These data were used in the empirical model to estimate tractional forces for each TMJ, and then mechanical work done and energy densities were calculated. Mechanical work (mJ) was on average 20 times greater in TMJs with disc displacement than in healthy TMJs (P<0.02). TMJs with disc displacement showed 350% more mechanical work (mJ) and 180% higher energy densities in women compared to men (P<0.02). A power analysis (alpha=0.05, beta=0.90) indicated that 40 women and 40 men would be required to detect a 50% difference in TMJ energy densities between genders. Mechanical work was significantly higher (P<=0.05) in TMJs with disc displacement compared to healthy TMJs, and mechanical work done and energy densities were significantly higher (P<=0.05) in TMJs with disc displacement in women compare to men. PMID- 26549917 TI - REGISTRATION OF ORTHODONTIC DIGITAL MODELS. AB - Current methods to assess outcomes and change in orthodontics are comparison of photographs, cephalometric measurements and superimpositions, and comparisons/measurements on dental casts. Digital models are a relatively new records modality in orthodontics. They offer numerous advantages in terms of storage space, spatial registration and superimposition. The purpose of this chapter is to determine the reproducibility of: 1) establishing occlusion of independently scanned digital models; and 2) registering digital models obtained after treatment on their homologous digital model setups produced before treatment. Reliability of both procedures was assessed with two random samples of five patient's models. In both experiments, three replicate positionings of the models per patient were created and variability in position was evaluated by the maximum surface difference between replicates, and the standard deviation of the surface distances between replicates respectively. Based on the data obtained, we concluded that it is reliable to register independently scanned models to a scanned surface of the models in occlusion. Surface-to-surface registration of final orthodontic digital models to planned setup models also is reproducible. PMID- 26549918 TI - Synthesis and characterization of ZnFe2O4 nanoparticles and its biomedical applications. AB - Biomedical applications of ZnFe2O4 nanoparticle are preferable among all kinds of ferrites due to the compatibility of Zn2+ ions for human bodies. We have followed the soft chemical route to synthesize chitosan and PEG coated ZnFe2O4 nanoparticles and also the chitosan-coated-nanoparticles encapsulated with liposome. X-ray diffraction studies by the Mo Kalpha target, showed the formation of single phase spinel structure. The lattice parameter turned out to be 8.48A and grain size ~ 4.8 nm (+/- 0.1 nm). Similar particle size was observed by transmission electron microscope analysis. HRTEM studies showed the distinct lattice fringes thus confirming the good crystallinity of the synthesized nanoparticles. M-H curve at room temperature showed the prepared sample was superparamagnetic in nature, which is also confirmed by the doublets of Mossbauer spectroscopy. Relaxivity values (r2) of Chitosan and PEG coated ZnFe2O4 nanoparticles are 68 and 76 mM-1s-1 respectively. In order to achieve further biocompatibility the chitosan-coated-nanoparticles were encapsulated with liposome. The r2 relaxivity was found as 54mM-1s-1. MR images obtained from the in vitro experiments based on phantoms demonstrated good contrast enhancement. Induction heating of bare and coated particles was investigated to reveal the self heating temperature rising properties of ZnFe2O4 nanoparticles. PMID- 26549919 TI - Relationship Involvement Among Young Adults: Are Asian American Men an Exceptional Case? AB - Asian American men and women have been largely neglected in previous studies of romantic relationship formation and status. Using data from the first and fourth waves of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examine romantic and sexual involvement among young adults, most of who were between the ages of 25 to 32 (N=11,555). Drawing from explanations that focus on structural and cultural elements as well as racial hierarchies, we examine the factors that promote and impede involvement in romantic/sexual relationships. We use logistic regression to model current involvement of men and women separately and find, with the exception of Filipino men, Asian men are significantly less likely than white men to be currently involved with a romantic partner, even after controlling for a wide array of characteristics. Our results suggest that the racial hierarchy framework best explains lower likelihood of involvement among Asian American men. PMID- 26549920 TI - Matrix Completion Discriminant Analysis. AB - Matrix completion discriminant analysis (MCDA) is designed for semi-supervised learning where the rate of missingness is high and predictors vastly outnumber cases. MCDA operates by mapping class labels to the vertices of a regular simplex. With c classes, these vertices are arranged on the surface of the unit sphere in c - 1 dimensional Euclidean space. Because all pairs of vertices are equidistant, the classes are treated symmetrically. To assign unlabeled cases to classes, the data is entered into a large matrix (cases along rows and predictors along columns) that is augmented by vertex coordinates stored in the last c - 1 columns. Once the matrix is constructed, its missing entries can be filled in by matrix completion. To carry out matrix completion, one minimizes a sum of squares plus a nuclear norm penalty. The simplest solution invokes an MM algorithm and singular value decomposition. Choice of the penalty tuning constant can be achieved by cross validation on randomly withheld case labels. Once the matrix is completed, an unlabeled case is assigned to the class vertex closest to the point deposited in its last c - 1 columns. A variety of examples drawn from the statistical literature demonstrate that MCDA is competitive on traditional problems and outperforms alternatives on large-scale problems. PMID- 26549922 TI - Microemulsion Synthesis of Iron Core/Iron Oxide Shell Magnetic Nanoparticles and Their Physicochemical Properties. AB - Iron magnetic nanoparticles were synthesized under an inert atmosphere via the reaction between FeCl3 and NaBH4 in droplets of water in a microemulsion consisting of octane with cetyl trimethylammonium bromide and butanol as surfactants. A thin Fe3O4 layer was produced on the iron nanoparticles using slow, controlled oxidation at room temperature. A silica shell was deposited on the Fe3O4 using 3-aminopropyltrimethoxysilane following the method of Zhang et al. [Mater. Sci. Eng. C 30 (2010) 92-97]. The structure and chemistry of the resulting nanoparticles were studied using variety of methods and their magnetic properties were determined. The diameter of the iron core was typically 8-16 nm, while the thickness of the Fe3O4 shell was 2-3 nm. The presence of the silica layer was confirmed using Fourier transform infra-red spectroscopy and the number of NH2-groups on each nanoparticle was determined based on colorimetric tests using ortho-phthalaldehyde. PMID- 26549923 TI - Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis. AB - OBJECTIVE: An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. METHODS: The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. RESULTS: The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. CONCLUSION: Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID- 26549924 TI - Allelic Imbalance of mRNA Associated with alpha2-HS Glycoprotein (Fetuin-A) Polymorphism. AB - Alpha 2-HS glycoprotein (AHSG), also designated as fetuin-A, exhibits polymorphism in population genetics consisting of two major alleles of AHSG(*) 1 and AHSG(*) 2. The serum level in the AHSG(*) 1 homozygote is significantly higher than that of the AHSG(*) 2 homozygote. This study examined the molecular mechanism for the cis-regulatory expression. To quantitate allele-specific mRNA in intra-assays of the heterozygote, RT-PCR method employing primers that were incorporated to the two closely located SNPs was developed. The respective magnitudes of AHSG(*) 1 to AHSG(*) 2 in the liver tissues and hepatic culture cells of PLC/PRF/5 were determined quantitatively as 2.5-fold and 6.2-fold. The mRNA expressional difference of two major alleles was observed, which is consistent with that in the serum level. The culture cells carried heterozygous genotypes in rs4917 and rs4918, but homozygous one in rs2248690. It was unlikely that the imbalance was derived from the SNP located in the promotor site. Furthermore, to investigate the effect of mRNA degradation, RNA synthesis in the cell culture was inhibited potently by the addition of actinomycin-D. No marked change was apparent between the two alleles. The results indicated that the cis regulatory expressional difference is expected to occur at the level of transcription or splicing of mRNA. PMID- 26549925 TI - Applying the Consensual Method of Estimating Poverty in a Low Income African Setting. AB - We present the first study of multidimensional poverty in Benin using the consensual or socially perceived necessities approach. There is a remarkable level consensus about what constitutes the necessities of life and an adequate standard of living. Following Townsend's concept of relative deprivation, we show how social consensus provides the basis for a reliable and valid index of multiple deprivation, which can be used to reflect multidimensional poverty. We discuss the issue of adaptive preferences, which has previously been used to criticise the consensual approach, and provide evidence to contest the claim that the poor adjust their aspirations downwards. PMID- 26549921 TI - The ecological foundations of transmission potential and vector-borne disease in urban landscapes. AB - Urban transmission of arthropod-vectored disease has increased in recent decades. Understanding and managing transmission potential in urban landscapes requires integration of sociological and ecological processes that regulate vector population dynamics, feeding behavior, and vector-pathogen interactions in these unique ecosystems. Vectorial capacity is a key metric for generating predictive understanding about transmission potential in systems with obligate vector transmission. This review evaluates how urban conditions, specifically habitat suitability and local temperature regimes, and the heterogeneity of urban landscapes can influence the biologically-relevant parameters that define vectorial capacity: vector density, survivorship, biting rate, extrinsic incubation period, and vector competence.Urban landscapes represent unique mosaics of habitat. Incidence of vector-borne disease in urban host populations is rarely, if ever, evenly distributed across an urban area. The persistence and quality of vector habitat can vary significantly across socio-economic boundaries to influence vector species composition and abundance, often generating socio economically distinct gradients of transmission potential across neighborhoods.Urban regions often experience unique temperature regimes, broadly termed urban heat islands (UHI). Arthropod vectors are ectothermic organisms and their growth, survival, and behavior are highly sensitive to environmental temperatures. Vector response to UHI conditions is dependent on regional temperature profiles relative to the vector's thermal performance range. In temperate climates UHI can facilitate increased vector development rates while having countervailing influence on survival and feeding behavior. Understanding how urban heat island (UHI) conditions alter thermal and moisture constraints across the vector life cycle to influence transmission processes is an important direction for both empirical and modeling research.There remain persistent gaps in understanding of vital rates and drivers in mosquito-vectored disease systems, and vast holes in understanding for other arthropod vectored diseases. Empirical studies are needed to better understand the physiological constraints and socio ecological processes that generate heterogeneity in critical transmission parameters, including vector survival and fitness. Likewise, laboratory experiments and transmission models must evaluate vector response to realistic field conditions, including variability in sociological and environmental conditions. PMID- 26549926 TI - Shale Failure Mechanics and Intervention Measures in Underground Coal Mines: Results From 50 Years of Ground Control Safety Research. AB - Ground control research in underground coal mines has been ongoing for over 50 years. One of the most problematic issues in underground coal mines is roof failures associated with weak shale. This paper will present a historical narrative on the research the National Institute for Occupational Safety and Health has conducted in relation to rock mechanics and shale. This paper begins by first discussing how shale is classified in relation to coal mining. Characterizing and planning for weak roof sequences is an important step in developing an engineering solution to prevent roof failures. Next, the failure mechanics associated with the weak characteristics of shale will be discussed. Understanding these failure mechanics also aids in applying the correct engineering solutions. The various solutions that have been implemented in the underground coal mining industry to control the different modes of failure will be summarized. Finally, a discussion on current and future research relating to rock mechanics and shale is presented. The overall goal of the paper is to share the collective ground control experience of controlling roof structures dominated by shale rock in underground coal mining. PMID- 26549927 TI - A Philosophical Concept of Deprivation and Its Use in the Attachment-Focused Treatment of Violence. AB - Theories in both contemporary psychotherapy and ancient philosophy associate deprivation with wrongdoing and suffering, but operate with different under standings of deprivation. The article will focus on two concepts of deprivation, one psychological and the other one ontological, as advanced by Bowlby in attachment theory, and Augustine of Hippo (354-430 CE). In attachment theory deprivation is something one suffers as a result of the others' actions (receipt of insensitive caregiving in early childhood); it has neuropsychological effects, it relates to violent behaviour later in life, and it is therapeutically treated mainly by emotional sensory work directed at attaining self-regulation. Understanding deprivation as Augustine does (i.e., diminishment of a being's inner unity and order caused by one's exercise of will) introduces a distinctive philosophical view on formation and can inform a type of reflective-behavioural work centred on forming impaired volitional and emotional capacities, and on reclaiming agency and responsibility both for what can be called self-deprivation and for ways to counter deprivation in offenders and victims. PMID- 26549928 TI - A Simple Method for Quick-Freezing. AB - In conventional freeze-fracture replicas produced from tissue cryoprotected with glycerol, the hydrophobic inner surfaces of membranes are revealed, but hydrophillic structures are obscured in the surrounding ice. Quick-freezing of tissue obviates the need for glycerol, which prevents the removal of this ice by etching or freeze-drying, but the major problem in freezing without glycerol cryoprotection is ice crystal formation. We describe here a simple method for quick-freezing tissue, in the absence of glycerol, on a nitrogen-cooled copper block with a hand-held specimen holder. This method freezes samples well enough to preserve molecular detail that can be revealed by subsequent etching. We show some examples of the quality of this freezing with respect to the visualization of molecular detail in isolated protein molecules such as ferritin and catalase. Furthermore, we show examples of in situ cellular structures that are revealed by this method, and we compare the structure seen in these replicas with structures preserved by quick-freezing at liquid helium temperatures. PMID- 26549929 TI - Toxic metal(loid) speciation during weathering of iron sulfide mine tailings under semi-arid climate. AB - Toxic metalliferous mine-tailings pose a significant health risk to ecosystems and neighboring communities from wind and water dispersion of particulates containing high concentrations of toxic metal(loid)s (e.g., Pb, As, Zn). Tailings are particularly vulnerable to erosion before vegetative cover can be reestablished, i.e., decades or longer in semi-arid environments without intervention. Metal(loid) speciation, linked directly to bioaccessibility and lability, is controlled by mineral weathering and is a key consideration when assessing human and environmental health risks associated with mine sites. At the semi-arid Iron King Mine and Humboldt Smelter Superfund site in central Arizona, the mineral assemblage of the top 2 m of tailings has been previously characterized. A distinct redox gradient was observed in the top 0.5 m of the tailings and the mineral assemblage indicates progressive transformation of ferrous iron sulfides to ferrihydrite and gypsum, which, in turn weather to form schwertmannite and then jarosite accompanied by a progressive decrease in pH (7.3 to 2.3). Within the geochemical context of this reaction front, we examined enriched toxic metal(loid)s As, Pb, and Zn with surficial concentrations 41.1, 10.7, 39.3 mM kg-1 (3080, 2200, and 2570 mg kg-1), respectively. The highest bulk concentrations of As and Zn occur at the redox boundary representing a 1.7 and 4.2 fold enrichment relative to surficial concentrations, respectively, indicating the translocation of toxic elements from the gossan zone to either the underlying redox boundary or the surface crust. Metal speciation was also examined as a function of depth using X-ray absorption spectroscopy (XAS). The deepest sample (180 cm) contains sulfides (e.g., pyrite, arsenopyrite, galena, and sphalerite). Samples from the redox transition zone (25-54 cm) contain a mixture of sulfides, carbonates (siderite, ankerite, cerrusite, and smithsonite) and metal(loid)s sorbed to neoformed secondary Fe phases, principally ferrihydrite. In surface samples (0-35 cm), metal(loid)s are found as sorbed species or incorporated into secondary Fe hydroxysulfate phases, such as schwertmannite and jarosites. Metal-bearing efflorescent salts (e.g., ZnSO4.nH2O) were detected in the surficial sample. Taken together, these data suggest the bioaccessibility and lability of metal(loid)s are altered by mineral weathering, which results in both the downward migration of metal(loid)s to the redox boundary, as well as the precipitation of metal salts at the surface. PMID- 26549930 TI - Multitasking With Television Among Adolescents. AB - Using Ecological Momentary Assessment, we explored predictors of adolescents' television (TV) multitasking behaviors. We investigated whether demographic characteristics (age, gender, race/ethnicity, and maternal education) predict adolescents' likelihood of multitasking with TV. We also explored whether characteristics of the TV-multitasking moment (affect, TV genre, attention to people, and media multitasking) predict adolescents' likelihood of paying primary versus secondary attention to TV. Demographic characteristics do not predict TV multitasking. In TV-multitasking moments, primary attention to TV was more likely if adolescents experienced negative affect, watched a drama, or attended to people; it was less likely if they used computers or video games. PMID- 26549931 TI - Personal narratives, well-being, and gender in adolescence. AB - Relations between narratives, especially the inclusion of internal state language within narratives, and well-being have been found in adults. However, research with adolescents has been sparse and the findings inconsistent. We examined gender differences in adolescents' personal autobiographical narratives as well as relations between internal state language and emotional well-being. Mirroring previous research with different age groups, we found that females narrate both positive and negative personal experiences in more emotional ways than do males. Also, adolescent females include more cognitive processing words indicative of self-reflection than do adolescent males. Adolescent males who told personal narratives richer in internal state language displayed higher levels of well being, but there were no relations between internal state language in personal narratives and well-being for adolescent females. These results are interpreted in terms of gender differences in emotional processing and understanding. Directions for future research are discussed. PMID- 26549932 TI - Enhancing understanding and improving prediction of severe weather through spatiotemporal relational learning. AB - Severe weather, including tornadoes, thunderstorms, wind, and hail annually cause significant loss of life and property. We are developing spatiotemporal machine learning techniques that will enable meteorologists to improve the prediction of these events by improving their understanding of the fundamental causes of the phenomena and by building skillful empirical predictive models. In this paper, we present significant enhancements of our Spatiotemporal Relational Probability Trees that enable autonomous discovery of spatiotemporal relationships as well as learning with arbitrary shapes. We focus our evaluation on two real-world case studies using our technique: predicting tornadoes in Oklahoma and predicting aircraft turbulence in the United States. We also discuss how to evaluate success for a machine learning algorithm in the severe weather domain, which will enable new methods such as ours to transfer from research to operations, provide a set of lessons learned for embedded machine learning applications, and discuss how to field our technique. PMID- 26549933 TI - Using random forests to diagnose aviation turbulence. AB - Atmospheric turbulence poses a significant hazard to aviation, with severe encounters costing airlines millions of dollars per year in compensation, aircraft damage, and delays due to required post-event inspections and repairs. Moreover, attempts to avoid turbulent airspace cause flight delays and en route deviations that increase air traffic controller workload, disrupt schedules of air crews and passengers and use extra fuel. For these reasons, the Federal Aviation Administration and the National Aeronautics and Space Administration have funded the development of automated turbulence detection, diagnosis and forecasting products. This paper describes a methodology for fusing data from diverse sources and producing a real-time diagnosis of turbulence associated with thunderstorms, a significant cause of weather delays and turbulence encounters that is not well-addressed by current turbulence forecasts. The data fusion algorithm is trained using a retrospective dataset that includes objective turbulence reports from commercial aircraft and collocated predictor data. It is evaluated on an independent test set using several performance metrics including receiver operating characteristic curves, which are used for FAA turbulence product evaluations prior to their deployment. A prototype implementation fuses data from Doppler radar, geostationary satellites, a lightning detection network and a numerical weather prediction model to produce deterministic and probabilistic turbulence assessments suitable for use by air traffic managers, dispatchers and pilots. The algorithm is scheduled to be operationally implemented at the National Weather Service's Aviation Weather Center in 2014. PMID- 26549934 TI - Synthesis and characterization of a multi-arm poly(acrylic acid) star polymer for application in sustained delivery of cisplatin and a nitric oxide prodrug. AB - Functionalized polymeric nanocarriers have been recognized as drug delivery platforms for delivering therapeutic concentrations of chemotherapies. Of this category, star-shaped multiarm polymers are emerging candidates for targeted delivery of anti-cancer drugs, due to their compact structure, narrow size distribution, large surface area and high water solubility. In this study, we synthesized a multi-arm poly(acrylic acid) star polymer via MADIX/RAFT polymerization and characterized it using NMR and size exclusion chromatography. The poly(acrylic acid) star polymer demonstrated excellent water solubility and extremely low viscosity, making it highly suited for targeted drug delivery. Subsequently, we selected a hydrophilic drug, cisplatin, and a hydrophobic nitric oxide-donating prodrug, O2-(2,4-dinitrophenyl) 1-[4-(2-hydroxy)ethyl]-3 methylpiperazin-1-yl]diazen-1-ium-1,2-diolate, as two model compounds to evaluate the feasibility of using poly(acrylic acid) star polymers for delivery of chemotherapeutics. After synthesizing and characterizing two poly(acrylic acid) star polymer-based nanoconjugates, poly(acrylic acid)-cisplatin (acid-Pt) and poly(acrylic acid)-nitric oxide prodrug (acid-NO), the in vitro drug release kinetics of both acid-Pt and acid-NO were determined at physiological conditions. In summary, we have designed and evaluated a polymeric nanocarrier for sustained delivery of chemotherapies, either as a single treatment or a combination therapy regimen. PMID- 26549935 TI - Porosity, permeability and 3D fracture network characterisation of dolomite reservoir rock samples. AB - With fractured rocks making up an important part of hydrocarbon reservoirs worldwide, detailed analysis of fractures and fracture networks is essential. However, common analyses on drill core and plug samples taken from such reservoirs (including hand specimen analysis, thin section analysis and laboratory porosity and permeability determination) however suffer from various problems, such as having a limited resolution, providing only 2D and no internal structure information, being destructive on the samples and/or not being representative for full fracture networks. In this paper, we therefore explore the use of an additional method - non-destructive 3D X-ray micro-Computed Tomography (MUCT) - to obtain more information on such fractured samples. Seven plug-sized samples were selected from narrowly fractured rocks of the Hauptdolomit formation, taken from wellbores in the Vienna basin, Austria. These samples span a range of different fault rocks in a fault zone interpretation, from damage zone to fault core. We process the 3D MUCT data in this study by a Hessian-based fracture filtering routine and can successfully extract porosity, fracture aperture, fracture density and fracture orientations - in bulk as well as locally. Additionally, thin sections made from selected plug samples provide 2D information with a much higher detail than the MUCT data. Finally, gas- and water permeability measurements under confining pressure provide an important link (at least in order of magnitude) towards more realistic reservoir conditions. This study shows that 3D MUCT can be applied efficiently on plug sized samples of naturally fractured rocks, and that although there are limitations, several important parameters can be extracted. MUCT can therefore be a useful addition to studies on such reservoir rocks, and provide valuable input for modelling and simulations. Also permeability experiments under confining pressure provide important additional insights. Combining these and other methods can therefore be a powerful approach in microstructural analysis of reservoir rocks, especially when applying the concepts that we present (on a small set of samples) in a larger study, in an automated and standardised manner. PMID- 26549937 TI - Psychological Outcome in Young Survivors of Severe TBI: A Cross-Informant Comparison. AB - OBJECTIVE: To investigate the psychological outcome and the agreement between self-ratings and proxy-ratings in young individuals after severe traumatic brain injury (TBI). METHODS: Twenty pairs of former patients who sustained a severe TBI in their adolescence or early adulthood and their significant others (SOs) were contacted around 66 months after injury to complete a measure of psychological and behavioral problems. The Adult Self-Report 18-59 and the Adult Behavior Checklist 18-59 were used. RESULTS: Results showed significant differences compared to the normative sample in the domains withdrawal, attention, and intrusive and internalizing problems. Good or excellent levels of agreement were found between the self-rating and the proxy-rating in overt areas such as somatic complaints and aggressive and intrusive behavior. Fair or poor levels of agreement were found in nonovert areas such as anxiety and depression, withdrawal, thought and attention problems, and personal strength. CONCLUSION: The findings show that young patients experience psychological dysfunction. Our study suggests that the use of either a self-rating or a proxy-rating would be appropriate for evaluating overt domains, regarding the good to excellent levels of agreement. However, in nonovert domains, such as withdrawal and attention, an additional proxy-rating from a SO could provide supplementary information and build a more complete objective assessment. PMID- 26549936 TI - Life after Adolescent and Adult Moderate and Severe Traumatic Brain Injury: Self Reported Executive, Emotional, and Behavioural Function 2-5 Years after Injury. AB - Survivors of moderate-severe Traumatic Brain Injury (TBI) are at risk for long term cognitive, emotional, and behavioural problems. This prospective cohort study investigated self-reported executive, emotional, and behavioural problems in the late chronic phase of moderate and severe TBI, if demographic characteristics (i.e., age, years of education), injury characteristics (Glasgow Coma Scale score, MRI findings such as traumatic axonal injury (TAI), or duration of posttraumatic amnesia), symptoms of depression, or neuropsychological variables in the first year after injury predicted long-term self-reported function. Self-reported executive, emotional, and behavioural functioning were assessed among individuals with moderate and severe TBI (N = 67, age range 15-65 years at time of injury) 2-5 years after TBI, compared to a healthy matched control group (N = 72). Results revealed significantly more attentional, emotional regulation, and psychological difficulties in the TBI group than controls. Demographic and early clinical variables were associated with poorer cognitive and emotional outcome. Fewer years of education and depressive symptoms predicted greater executive dysfunction. Younger age at injury predicted more aggressive and rule-breaking behaviour. TAI and depressive symptoms predicted Internalizing problems and greater executive dysfunction. In conclusion, age, education, TAI, and depression appear to elevate risk for poor long-term outcome, emphasising the need for long-term follow-up of patients presenting with risk factors. PMID- 26549938 TI - Mixing in microfluidic devices and enhancement methods. AB - Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel's hydraulic diameter, flow velocity, and solution's kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types. PMID- 26549939 TI - Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension. AB - The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-beta, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism. PMID- 26549940 TI - Mediators of Inflammation: Inflammation in Cancer, Chronic Diseases, and Wound Healing. PMID- 26549941 TI - Association of Adipokines with Insulin Resistance, Microvascular Dysfunction, and Endothelial Dysfunction in Healthy Young Adults. AB - Proinflammatory adipokines (inflammation markers) from visceral adipose tissue may initiate the development of insulin resistance (IR) and endothelial dysfunction (ED). This study's objective was to investigate the association of five inflammation markers (CRP and four adipokines: IL-6, TNFalpha, PAI-1, and adiponectin) with IR (quantitative insulin resistance check index (QUICKI)), microvascular measures (capillary density and albumin-to-creatinine ratio (ACR)), and endothelial measures (forearm blood flow (FBF) increases from resting baseline to maximal vasodilation). Analyses were conducted via multiple linear regression. The 295 study participants were between 18 and 45 years of age, without diabetes or hypertension. They included 24% African Americans and 21% Asians with average body mass index of 25.4 kg/m(2). All five inflammation markers were significantly associated with QUICKI. All but adiponectin were significantly associated with capillary density, but none were associated with ACR. Finally, IL-6 and PAI-1 were significantly associated with FBF increase. We also identified a potential interaction between obesity and IL-6 among normal weight and overweight participants: IL-6 appeared to be positively associated with QUICKI and capillary density (beneficial effect), but the inverse was true among obese individuals. These study findings suggest that inflammation measures may be potential early markers of cardiovascular risk in young asymptomatic individuals. PMID- 26549944 TI - Heterotopic ossification after hemiarthroplasty of the hip - A comparison of three common approaches. AB - OBJECTIVE: Heterotopic ossification (HO) about the hip after total hip arthroplasty and internal fixation of the hip, pelvis, and acetabulum has been linked to surgical approach. However, no study has investigated surgical approach and HO in patients undergoing hemiarthroplasty. We therefore aimed to explore the influence of operative approach in patients undergoing hemiarthroplasty. METHODS: Through a retrospective case series at an Urban level I trauma center, we found 80 patients over the age of 60 undergoing hemiarthroplasty for femoral neck fractures from 2000 to 2009. Patient charts, operative notes, and radiographs were reviewed for demographics, operative approach (anterior: A, anterior lateral: AL, posterior: P), and any development of HO. Fisher's exact test compared rates of HO among the three approaches. Student's t-tests compared Brooker Classification levels of HO among the approaches. RESULTS: 82 hemiarthroplasties (26 A, 32 AL, 24 P) were included for analysis. 22 patients (27%) had HO. There was no significant difference in the development of HO based upon surgical approach: A: 19% (n = 5); AL: 34% (n = 11); P: 25% (n = 6). There was a significant difference in the grade of HO based on Brooker Classification (BC) with the posterior approach resulting in significantly lower grade of HO: A (BC: 2.60); AL (BC: 2.64); P (BC: 1.50) (p = 0.012). CONCLUSIONS: Our data is the first to evaluate surgical approach and HO in patients with hemiarthroplasty. Patients have a significant risk of developing higher grade HO based on surgical approach (A or AL). Orthopedists should be mindful of these risks when considering A or AL approaches. PMID- 26549943 TI - HSP90 and HSP70: Implication in Inflammation Processes and Therapeutic Approaches for Myeloproliferative Neoplasms. AB - Myeloproliferative neoplasms (MPN) are clonal stem cell disorders that lead to the excessive production of one or more blood cell lineages. It has been reported that, in most MPN, inflammatory cytokines are frequently increased, indicating that inflammation plays a crucial role in these disorders. Heat shock proteins (HSP) are induced in response to many stressful conditions from heat shock to hypoxia and inflammation. Besides their chaperone and cytoprotective functions, HSPs are key players during inflammation, hence the term "chaperokine." Through their chaperone activity, HSP90, a stabilizer of many oncogenes (e.g., JAK2), and HSP70, a powerful antiapoptotic chaperone, tightly regulate Nuclear Factor-kappa B signalling, a critical pathway in mediating inflammatory responses. In light of this potential, several HSP90 inhibitors have been generated as anticancer agents able to degrade oncogenes. As it turns out, however, these drugs are also potent inhibitors of the inflammatory response in various diseases. Given the chaperone potential of HSP70 and the fact that HSP90 inhibitors induce HSP70, interest in HSP70 inhibitors is also increasing. Here, we focus on the implication of HSP90 and HSP70 in inflammatory responses and on the emergence of new therapeutic approaches in MPN based on HSP inhibitors. PMID- 26549945 TI - Comparative study of fresh femoral neck fractures managed by multiple cancellous screws with and without fibular graft in young adults. AB - OBJECTIVES: Aim of our study was to assess the role of addition of fibular strut graft to multiple cancellous screws in functional outcome, union and complications associated with those managed by only multiple cancellous screws in fresh femoral neck fractures. METHODS: A randomized control trial study was conducted on the patients of femoral neck fractures managed with multiple cancellous screws (group A) and multiple cancellous screws with fibular graft (group B). Patients aged between 20 and 50 years, having Gardens type III or IV fracture with duration of injury less than two weeks were included in the study. RESULTS: Eighty seven cases were analysed n = 45 were in group A and n = 42 in group B. Functional outcome (Harris hip score) was excellent in 30 patients in group A as compared to 12 in Group B which was statistically significant favouring group A. The time of full weight bearing, union and non union rates showed no statistical significance (p > 0.05). On statistical grounds none of the procedures proved to be better than other. CONCLUSIONS: Fresh femoral neck fracture in young adults managed with multiple cancellous screws fixation with fibular graft has no added advantage over multiple cancellous screws fixation alone. PMID- 26549946 TI - The clinical profile of musculoskeletal injuries in children attending a major hospital in Delhi, India. AB - BACKGROUND: Children are vulnerable to musculoskeletal injuries both at home and on the street for various reasons. Morbidity and disabilities resulting from these, mostly preventable, injuries, make them a burden to their families and society. The role of various factors associated with injuries is often not documented. METHODS: This prospective study, done on 100 children aged up to 12 years with musculoskeletal trauma, analysed in details, the various modes of injuries. RESULTS: One in every five patient was a child below 12 years of age. Boys were injured more than girls. Injuries, especially fractures, were most common in the extremities, the upper limb more commonly injured than the lower limb. Most of the injuries occurred at home. The most common mode of injuries was falls that happened while playing both within and outside the home, followed by road traffic accidents. Most injuries occurred during daytime. CONCLUSIONS: Injuries in children were found to be preventable. Small interventions while constructing homes can contribute tremendously to injury prevention and control in children. Parental awareness about the various modes of injury, role of supervised playing and their responsibility towards injury prevention can play a key role in reducing the morbidity associated with childhood fractures. PMID- 26549942 TI - Interleukin-1 Family Cytokines in Liver Diseases. AB - The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL 1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL 33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases. PMID- 26549947 TI - Revision knee arthroplasty with a rotating-hinge design in elderly patients with instability following total knee arthroplasty. AB - BACKGROUND: Revision knee arthroplasty with a rotating-hinge design could be an option for the treatment of instability following total knee arthroplasty (TKA) in elderly patients. PURPOSE: To evaluate the clinical and radiographic results of revision arthroplasties in TKAs with instability using a rotating-hinge design in elderly patients. METHODS: We retrospectively reviewed 96 rotating-hinge arthroplasties. The average age of the patients was 79 years (range, 75-86 years); the minimum follow-up was 5 years (mean, 7.3 years; range, 5-10 years). Patients were evaluated clinically (Knee Society score) and radiographically (position of prosthetic components, signs of loosening, bone loss). RESULTS: At a minimum followup of 5 years (mean, 7.3 years; range, 5-10 years), Knee Society pain scores improved from 37 preoperatively to 79 postoperatively, and function scores improved from 34 to 53. ROM improved on average from -15 degrees of extension and 80 degrees of flexion before surgery to -5 degrees of extension and 120 degrees of flexion at the last followup (p = 0.03). No loosening of implants was observed. Nonprogressive radiolucent lines were identified around the femoral and tibial components in 2 knees. One patient required reoperation because of a periprosthetic infection. CONCLUSIONS: Revision arthroplasty with a rotating-hinge design provided substantial improvement in function and a reduction in pain in elderly patients with instability following TKA. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26549949 TI - Pseudo-winging of scapula due to benign lesions of ventral surface of scapula - Two unusual causes. AB - Winging of the scapula due to benign lesion of ventral surface of scapula is one of the rare cause and difficult to diagnose in first place. We present two unusual cases of pseudo winging of scapula due to benign lesions of scapula. First case was of 23 year old male with solitary osteochondroma of ventral surface of scapula. Second was 38 year old female with hemangioma involving subscapular muscles. Both the patients presented to us with dull aching pain over right scapular and shoulder region of 6 months duration with gradually increasing pseudo-winging of scapula. On examination there was mild tenderness over superomedial border of scapula with scapular snapping(5) or 'clunk' on hyper abduction of shoulder. Further radiographic evaluation of right scapular region revealed solitary osteochondroma of ventral surface of right scapula in first case whereas MRI revealed hemangioma of subscapular muscles in second case. Hemangioma was initially treated by weekly injecting sclerosing agent (Inj. Polidocanol) locally for 4 weeks. Both lesions were later treated by excision and subsequent follow up revealed disappearance of pain and winging of scapula. CONCLUSION: Winging of the scapula due to solitary osteochondroma and subscapular hemangioma of the scapula may present with an initial diagnostic difficulty but appropriate knowledge of literature and diagnostic acumen can give excellent results. PMID- 26549948 TI - Management of diabetic foot: Brief synopsis for busy orthopedist. AB - According to available medical reports, over 10% of diabetic patients will develop foot ulcers during their lifetimes. This condition still remains great challenges to many clinicians. Various mechanisms may explain treatment-resistant entity. Treatment varies widely, relying on the severity of the ulceration as well as the presence of infection or ischemia. However, the most important things to keep in mind should consist of the following: 1) appropriate debridement; 2) off-loading of pressure; 3) effective control of infection; 4) local wound care strategy; 5) timely reconstructive surgery. The ideal flap for diabetic foot reconstruction should provide a well-vascularized tissue to control infection, adequate contour for footwear, durability, and solid anchorage to resist shearing forces. A thorough assessment of patient's general condition and voluntary motivation of the patient should be warranted to prevent any sort of postoperative recurrence. PMID- 26549950 TI - An isolated dorso-medial dislocation of navicular bone: A case report. AB - An isolated dislocation of tarsal navicular is extremely rare injury. Usually it is associated with fracture of navicular itself or other tarsal bones of foot along with disruption of medial or lateral column of foot. Mechanism of injury is complex but usually a severe abduction force is required to produce such injury in a planter flexed foot. A 30 year old male presented with isolated navicular dislocation. Management required open reduction and fixation with k-wires. These injuries have specific complications including avascular necrosis of navicular and post-traumatic arthritis. PMID- 26549951 TI - Cysticercosis of Soleus muscle presenting as isolated calf pain. AB - CNS is the most common site of involvement by cysticercosis. Symptomatic involvement of isolated skeletal muscle by solitary cysticercosis cyst is extremely rare. We report a rare and unusual case of cysticercosis presenting as acute calf pain, which is a diagnostic challenge. But the diagnosis was reached by sero-radiological examination and patient was managed conservatively by medical means. PMID- 26549952 TI - Isolated volar fracture-dislocation of the base of the second metacarpal bone by indirect injury. AB - Isolated volar fracture-dislocation of the second carpometacarpal joint is extremely rare, and no case of indirect injury has been reported. We are presenting a case of indirect injury, treated by open reduction with volar approach. Three-dimensional computed tomography was helpful for confirming and making surgical plan for this injury. PMID- 26549953 TI - Non-union coronal fracture femoral condyle, sandwich technique : A case report. AB - Coronal fractures of the femoral condyle (Hoffa fracture) are rare injuries but can be managed with satisfactory outcome if properly treated. We discuss an unusual case of a young adult male presenting with 9 month old neglected Hoffa fracture with pain, stiffness and limitation of knee movement, managed with sandwich bone grafting technique.(1). PMID- 26549954 TI - Quiz. PMID- 26549955 TI - Errata. AB - [This corrects the article DOI: 10.11919/j.issn.1002-0829.215026.]. PMID- 26549956 TI - Challenges to the uniqueness of psychotic experience in psychosis: insights on research methodology and intervention. AB - Paul Bebbington's recent Special Article on the value of psychosocial epidemiology as a tool for understanding the symptomatology of psychosis provides a fresh perspective on understanding the etiology of schizophrenia and related psychotic conditions. Assessment of psychotic-like experiences in non-clinical populations may help to clarify the role of non-psychotic symptoms such as anxiety and depression in the onset and course of psychotic disorders. This approach may also make it possible to expand the repertoire of interventions for preventing the onset or ameliorating the course of psychotic conditions. There is, however, a long road to travel before the mapping of the relationships between brain pathology, psychological symptoms, environmental stressors, and clinical diagnoses are sufficiently detailed to merit the creation of a new psychiatric nosology. PMID- 26549957 TI - Efficacy and safety of treating patients with refractory schizophrenia with antipsychotic medication and adjunctive electroconvulsive therapy: a systematic review and meta-analysis. AB - BACKGROUND: The efficacy and safety of the combined treatment of refractory schizophrenia with antipsychotic medications and electroconvulsive therapy (ECT) remain uncertain. AIMS: Conduct systematic review and meta-analysis of available literature in English and Chinese about ECT in the treatment of refractory schizophrenia. METHODS: English and Chinese databases were searched for studies published prior to May 20, 2015 regarding the efficacy and safety of the combined treatment of refractory schizophrenia with antipsychotic medications and ECT. Two researchers selected and evaluated studies independently using pre-defined criteria. Review Manager 5.3 software was used for data analysis. RESULTS: A total of 22 randomized control studies, 18 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 18 of the 22 studies with a pooled sample of 1394 individuals found that compared to treatment with antipsychotic medications alone, combined treatment with antipsychotic medications and ECT had significantly higher rates of achieving study-specific criteria of 'clinical improvement' (RR=1.25, 95%CI=1.14-1.37). Based on the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, the quality of evidence for this assessment of efficacy was 'moderate'. However, the proportion of participants who experienced headache during the treatment was significantly higher in the combined treatment group (RR=9.10, 95%CI=3.97-20.86, based on a pooled sample of 517 from 8 studies) and the proportion who experienced memory impairment was also higher in the combined treatment group (RR=6.48, 95%CI=3.54-11.87, based on a pooled sample of 577 from 7 studies). The quality of evidence about these adverse events was rated as 'very low'. CONCLUSIONS: There are very few high quality randomized controlled clinical trials about the combination of antipsychotic medications and ECT in the treatment of refractory schizophrenia. This meta-analysis found that the combination of antipsychotic medications and ECT could improve psychiatric symptoms in patients with refractory schizophrenia, but the incomplete methodological information provided for most of the studies, publication bias (favoring studies with better outcomes in the combined treatment group), and the low quality of evidence about adverse outcomes, cognitive impairment, and overall functioning raise questions about the validity of the results. PMID- 26549958 TI - Single-blind, randomized controlled trial of effectiveness of Naikan therapy as an adjunctive treatment for schizophrenia over a one-year follow-up period. AB - BACKGROUND: Current treatments for schizophrenia are often only partially effective. AIMS: Assess the possible benefit of using adjunctive Naikan therapy, a cognitive approach based on self-reflection that originated in Japan for the treatment of schizophrenia. METHODS: After resolution of acute psychotic symptoms, 235 psychiatric inpatients with schizophrenia who had a middle school education or higher were randomly assigned to a control group (n=112) that received routine medication and inpatient rehabilitative treatment or an intervention group (n=123) that also received adjunctive Naikan therapy for 2 hours daily, 5 days a week for 4 weeks. The patients were then discharged and followed up for 12 months. The Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance scale (PSP), and Insight and Attitude Questionnaire (ITAQ) were used to assess patients at enrollment, after the 1 month intervention, and after the 12-month follow-up. Evaluators were blind to the group assignment of patients. RESULTS: Only 13 (10.6%) of the intervention group participants relapsed over the 12-month follow-up, but 23 (20.5%) control group participants relapsed (X(2)=4.50, p=0.034). Using a modified intention-to treat analysis and a repeated measure analysis of variance, the PANSS, PSP, and ITAQ total scores all showed significantly greater improvement over the 12-month follow-up in the Naikan group than in the control group. The drop in mean chlorpromazine-equivalent dosage from enrollment to the end of follow-up was significantly different in the intervention group but not in the control group, though the change in dosage over time between groups was not statistically significant. CONCLUSIONS: This study provides robust support for the effectiveness of Naikan therapy as an adjunctive treatment during the recovery period of schizophrenia. Compared to treatment as usually, adjunctive Naikan therapy can sustain the improvement in psychotic symptoms achieved during acute treatment, improve insight about the illness, enhance social functioning, and reduce relapse over a one-year follow-up period. Further research of this treatment with larger and more diverse samples of patients with schizophrenia is merited. PMID- 26549959 TI - Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind, double-dummy, randomized controlled clinical trial. AB - BACKGROUND: This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603). AIMS: Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD). METHODS: This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40-60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial. Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention to-treat (ITT) method with 146 in the experimental group and 150 in the control group. RESULTS: Both groups experienced 29 dropouts during the 8-week trial. HAMD 17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X(2)=0.62 p=0.433), remission rate (41.1% v. 51.3%, X(2)=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X(2)=0.14, p=0.705). CONCLUSIONS: Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China. PMID- 26549960 TI - Comparison of the effectiveness of duloxetine in depressed patients with and without a family history of affective disorders in first-degree relatives. AB - BACKGROUND: It remains unclear whether or not a positive family history of affective disorders predicts the effectiveness of antidepressant treatment of depression. AIMS: Assess the relationship of a family history of affective disorders to the efficacy of duloxetine in the treatment of depressive disorder. METHODS: Seventy-seven patients with depressive disorder (as defined by the 10th edition of the International Classification of Diseases, ICD-10) were enrolled in the study and treated with standard doses of duloxetine for 12 weeks. Among these patients 37 had a family history of affective disorder in first-degree relatives and 40 did not. The Hamilton Depression rating scale (HAMD-17), Hamilton Anxiety rating scale (HAMA), Side Effects Rating Scale (SERS), Snaith-Hamilton Pleasure Scale (SHAPS), and Beck Depression Inventory (BDI) were assessed at baseline and at the end of the 2(nd), 4(th), 6(th), 8(th), and 12(th) week after enrollment. Repeated measures analysis of variance and logistic regression were used to analyze the association between a family history of affective disorders and the efficacy of duloxetine. RESULTS: Patients with a positive family history of affective disorders had an earlier age of onset, a longer duration of illness, a higher level of psychic anxiety, and more prominent anhedonia. Repeated measures analysis of variance showed a significant improvement in the severity of depression over the 12 weeks but no differences in the magnitude or speed of improvement between the two groups. Treatment was considered effective (i.e., drop in baseline HAMD-17 total score of >=50%) in 75.7% of those with a family history of affective disorders and in 77.5% of those without a family history (X(2)=0.04, p=0.850). CONCLUSIONS: Family history of affective disorders is not associated with the effectiveness of duloxetine in the acute treatment of depressive disorder. PMID- 26549961 TI - Comorbid bipolar disorder and obsessive-compulsive disorder. AB - Obsessive-compulsive symptoms are common in patients with bipolar disorders. This comorbid condition complicates the clinical treatment of the two disorders, so identifying these individuals is important. We discuss the comorbid occurrence of obsessive-compulsive disorder and bipolar disorder, introduce possible etiological mechanisms that could result in this common comorbid condition, discuss recent research advances in the area, and propose some clinical principles for managing such patients. PMID- 26549962 TI - Obsessive compulsive symptoms in bipolar disorder patients: a comorbid disorder or a subtype of bipolar disorder? AB - Over the last decade increasing attention has been focused on individuals that simultaneously meet the criteria of two or more mental disorders. One of these comorbid conditions, comorbid bipolar disorder and obsessive compulsive disorder, is relatively common among patients with a primary diagnosis of bipolar disorder. But there is little research about the diagnosis and treatment of this comorbid condition, particularly in China. The available studies are primarily cross sectional studies with small samples, so they are of limited use in understanding the etiology and course of this combined condition. A review of the limited literature suggests that this is a relatively severe, refractory subtype of bipolar disorder that only occasionally merits being considered a comorbid disorder. Larger prospective studies are needed to clarify the etiology, prognosis, and appropriate treatment for this comorbid condition. PMID- 26549963 TI - Case report of comorbid schizophrenia and obsessive compulsive disorder in a patient who was tube-fed for four years by family members because of his refusal to eat. AB - Refusal to eat is a common presentation in many psychiatric disorders including obsessive compulsive disorder and schizophrenia. In the acute situation it may be a medical emergency; when it becomes chronic it can become an ingrained behavior that is difficult to change. The diagnosis of individuals who refuse to eat may be difficult, particularly in persons with comorbid medical problems, impaired intelligence, or lack of insight into their condition. Tube-feeding is an effective short-term intervention that can be discontinued when the patient re starts oral intake. However, in some situations patients may become dependent on the use of tube-feeding. We present a case report of a patient with schizophrenia, obsessive compulsive disorder, borderline intelligence, and seizure disorder who was tube-fed by his family members for more than three years because he refused to eat orally. PMID- 26549964 TI - Introduction to longitudinal data analysis in psychiatric research. AB - The onset, course, and management of mental health problems typically occur over relatively long periods of time, so a substantial proportion of psychiatric research - particularly the research that can provide clear answers about the complex interaction of biological, psychological, and social factors - requires multiple assessments of individuals and the environments in which they live over time. However, many psychiatric researchers use incorrect statistical methods to analyze this type of longitudinal data, a problem that can result in unrecognized bias in analytic results and, thus, incorrect conclusions. This paper provides an introduction to the topic of longitudinal data analysis. It discusses the different dataset structures used in the analysis of longitudinal data, the classification and management of missing data, and methods of adjusting for intra individual correlation when developing multivariate regression models using longitudinal data. PMID- 26549965 TI - Convergence and Stability of a Class of Iteratively Re-weighted Least Squares Algorithms for Sparse Signal Recovery in the Presence of Noise. AB - In this paper, we study the theoretical properties of a class of iteratively re weighted least squares (IRLS) algorithms for sparse signal recovery in the presence of noise. We demonstrate a one-to-one correspondence between this class of algorithms and a class of Expectation-Maximization (EM) algorithms for constrained maximum likelihood estimation under a Gaussian scale mixture (GSM) distribution. The IRLS algorithms we consider are parametrized by 0 < nu <= 1 and epsilon > 0. The EM formalism, as well as the connection to GSMs, allow us to establish that the IRLS(nu, epsilon) algorithms minimize epsilon-smooth versions of the l nu 'norms'. We leverage EM theory to show that, for each 0 < nu <= 1, the limit points of the sequence of IRLS(nu, epsilon) iterates are stationary point of the epsilon-smooth l nu 'norm' minimization problem on the constraint set. Finally, we employ techniques from Compressive sampling (CS) theory to show that the class of IRLS(nu, epsilon) algorithms is stable for each 0 < nu <= 1, if the limit point of the iterates coincides the global minimizer. For the case nu = 1, we show that the algorithm converges exponentially fast to a neighborhood of the stationary point, and outline its generalization to super-exponential convergence for nu < 1. We demonstrate our claims via simulation experiments. The simplicity of IRLS, along with the theoretical guarantees provided in this contribution, make a compelling case for its adoption as a standard tool for sparse signal recovery. PMID- 26549966 TI - Affective Self-Regulation Trajectories During Secondary School Predict Substance Use Among Urban Minority Young Adults. AB - This study explored the relationship between trajectories of affective self regulation skills during secondary school and young adult substance use in a large multi-ethnic, urban sample (N = 995). During secondary school, participants completed a measure of cognitive and behavioral skills used to control negative, unpleasant emotions or perceived stress. As young adults, participants reported on the frequency and quantity of their alcohol, cigarette, and marijuana use in a telephone interview. Controlling for demographic variables, self-regulation did not significantly change over adolescence, although there was significant variation in participants' rates of growth and decline. Lower seventh grade self regulation and less steep increases in self-regulation were predictive of higher young adult substance use. Male participants had significantly lower initial self regulation and higher young adult substance use. The results suggest that interventions that build affective self-regulation skills in adolescence may decrease the risk of young adult substance use. PMID- 26549967 TI - Effects of Meditation on Symptoms of Knee Osteoarthritis. AB - OBJECTIVE: The aim of this study was to investigate changes in knee pain, function, and related indices in older adults with osteoarthritis (OA) of the knee, following an 8-week meditation program. METHODS: Eleven community-dwelling adults with physician- confirmed knee OA were enrolled in the study. Core outcomes included recommended measures of knee pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] and 11-point numeric rating scale [NRS]), function (WOMAC), and perceived global status (patient global assessment). Additional outcomes included: perceived stress; stress hardiness; mood; sleep; and sympathetic activation. Following baseline assessment, participants were trained briefly in mantra meditation and instructed to meditate for 15-20 minutes twice daily for 8 weeks, and to record each practice session on a daily log. Changes over time were analyzed using paired t-tests. RESULTS: Nine participants (82%) completed the study. Participants had statistically significant improvements in all core outcomes: knee pain (WOMAC: 47.7% +/- 25.1% reduction, P = 0.001; NRS: 42.6% +/- 34.6% reduction, P < 0.01); function (44.8% +/- 29.9, P = 0.001); and global status (45.7% +/- 36.5, P = 0.01); as well as knee stiffness (P = 0.005), mood (P = 0.05), and a WOMAC proxy for sleep disturbance (P = 0.005). CONCLUSIONS: Findings from this pilot study suggest that a mantra meditation program may help reduce knee pain and dysfunction, as well as improving mood and related outcomes in adults with knee OA. PMID- 26549968 TI - Classroom Race/Ethnic Composition, Family-School Connections, and the Transition to School. AB - Using data from the Early Childhood Longitudinal Study-Kindergarten Cohort (N = 13,970), we examined whether two aspects of school-family connections-parental involvement and communication quality-accounted for the association between classroom composition and children's academic and socioemotional functioning following the transition to elementary school. For students with more same race/ethnic representation in their classrooms, greater classroom race/ethnic diversity promoted more parental involvement, which in turn promoted children's interpersonal skills and reading achievement. Classroom diversity made little difference on parental involvement when students had fewer same-race/ethnic peers in the classroom. Teacher-parent communication quality did not emerge as an explanatory mechanism, and findings did not vary by the race/ethnic match between students and their teachers. PMID- 26549970 TI - Immunohistochemical Markers of Soft Tissue Tumors: Pathologic Diagnosis, Genetic Contributions, and Therapeutic Options. AB - After ~30 years of widespread usage, immunohistochemistry (IHC) has become a standard method of diagnosis for surgical pathology. Because of the plethora of diagnoses and often subtle nature of diagnostic criteria, IHC finds particular utility in soft tissue tumors. The use of progressively small amounts of tissue for diagnosis highlights the importance of this method. The sensitivity and crispness of IHC stains have progressively improved with the advent of new techniques. Traditionally, IHC detects cell-typic markers that characterize cell phenotypes, such as chromogranin for neuroectodermal tissue, myogenin for skeletal muscle, and cytokeratin for epithelium. However, the advent of genetic discoveries have led to IHC testing for detection of fusion gene products or overexpressed oncogenes associated with deletions and mutations. Proliferation based markers such as Ki-67 can also be used for prognosis and grading, but more standardization is needed. Development of monoclonal antibody-based pharmaceuticals, such as imatinib or crizotinib, holds the promise of tailored anticancer therapy. IHC thus has assumed importance not only for diagnosis but also for guidance of personalized medicine. PMID- 26549969 TI - Regeneration in the nervous system with erythropoietin. AB - Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system. PMID- 26549971 TI - Trends in Alcohol's Harms to Others (AHTO) and Co-occurrence of Family-Related AHTO: The Four US National Alcohol Surveys, 2000-2015. AB - Various harms from others' drinking have been studied individually and at single points in time. We conducted a US population 15-year trend analysis and extend prior research by studying associations of depression with combinations of four harms - family/marriage difficulties, financial troubles, assault, and vandalism attributed to partners or family members. Data come from four National Alcohol Surveys conducted by telephone in 2000, 2005, 2010, and 2015 (analytic sample = 21,184). Weighted logistic regression models estimated time trends adjusting for victim characteristics (gender, age, race/ethnicity, marital status, poverty, employment, family history of alcohol problems, and drinking maximum). The 2015 survey asked the source of the harm; we used similar models to examine characteristics, including anxiety and depression, associated with various combinations of family/marriage, financial, and assault harms due to partner's/spouse's/family members' drinking. A significant upward trend (P <0.001) from 2000 to 2015 was seen for financial troubles but not for other harms due to someone else's drinking. In 2015, depression and/or anxiety were strongly associated with exposures to harms and combinations of harms identified as stemming from drinking spouse/partner and/or family members. The results shed new light on 15-year trends and associations of harms with personal characteristics. A replicated finding is how the victim's own heavy drinking pattern is implicated in risks for exposures to harms from someone else's drinking. Documenting risk factors for and mental health impacts is important for interventions to reduce alcohol's harm to others. PMID- 26549972 TI - Overview of the Benzene and Other Toxics Exposure (BEE-TEX) Field Study. AB - The Benzene and other Toxics Exposure (BEE-TEX) field study was an experimental campaign designed to demonstrate novel methods for measuring ambient concentrations of hazardous air pollutants (HAPs) in real time and to attribute these concentrations to quantified releases from specific emission points in industrial facilities while operating outside facility fence lines. BEE-TEX was conducted in February 2015 at three neighboring communities in the Houston Ship Channel of Texas, where a large number of petrochemical facilities are concentrated. The novel technologies deployed during BEE-TEX included: (1) tomographic remote sensing based on differential optical absorption spectroscopy; (2) real-time broadcasting of ambient air monitoring data over the World Wide Web; (3) real-time source attribution and quantification of HAP emissions based on either tomographic or mobile measurement platforms; and (4) the use of cultured human lung cells in vitro as portable indicators of HAP exposure. PMID- 26549973 TI - Associations of the A66G Methionine Synthase Reductase Polymorphism in Colorectal Cancer: A Systematic Review and Meta-Analysis. AB - Inconsistency in the reported associations between the A66G polymorphism in the methionine synthase reductase (MTRR) gene and colorectal cancer (CRC) prompted a meta-analysis, so that we could obtain a more precise estimate. Databases searches of the published literature yielded 20 case-control studies from 17 articles (8,371 cases and 12,574 controls). We calculated pooled odds ratios (ORs) and 95% confidence intervals in three genetic comparisons (A allele, G allele, and A/G genotype). We found no evidence of overall associations between MTRR A66G and CRC risk (OR 0.96-1.05, P = 0.12-0.44). This was materially unchanged when reanalyzed without the Hardy-Weinberg equilibrium (HWE)-deviating studies (OR 0.97-1.06, P = 0.11-0.65). In the A allele comparison, however, outlier treatment generated significant protection (OR 0.91, P = 0.01). Combined removal of the outliers and HWE-deviating studies reflected this summary effect (OR 0.90, P = 0.01) as did the pooled OR from high-quality studies (OR 0.90, P = 0.01). Only the Asian subgroup showed significant (both at P = 0.05) A allele (OR 1.13) and A/G genotype (OR 0.88) associations. In conclusion, post-outlier A allele effects were protective. Our study also suggests ethnic-specific associations with Asian susceptibility and protection in the A allele and A/G genotype comparisons, respectively. Folate status showed no association of this polymorphism with CRC. PMID- 26549974 TI - ASCORBIC ACID - MODULATION OF ARSENIC TRIOXIDE TOXICITY: IMPLICATION FOR THE CLINICAL TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA. AB - BACKGROUND: Acute Promyelocytic Leukemia (APL) is a subtype of acute leukemia which can affect people of any age. It strikes about 1,500 patients in the United States each year. Recent in vitro and in vivo studies have shown that arsenic trioxide (ATO) can induce clinical remission in de-novo and APL patients that have relapsed from conventional treatment. Ascorbic acid (AA) is an anti-oxidant and free radical scavenger effective against peroxyl- and hydroxyl-radicals, superoxide, singlet oxygen and peroxynitrite. Although research has shown that AA can prevent cancer by deactivating free radicals before they can damage DNA and initiate tumor growth, there are also published reports indicating that it may act as a pro-oxidant that helps the body's own free radical defense mechanism destroy tumors in their early stages. AIM: The aim of this research was to study the modulatory effect of AA on ATO-induced oxidative stress in leukemia cells. METHODS: In the present investigation, we performed the MTT assay and trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) production in HL-60 cells co exposed to ascorbic acid (AA) and ATO. RESULTS: The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in MDA levels with increasing doses of AA. From these results, we concluded that the addition of the ascorbic acid to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS). CONCLUSIONS: Based on these direct in vitro findings, our study provides evidence that AA may extend the therapeutic spectrum of ATO, and improve the clinical outcome associated with ATO monotherapy in vivo. PMID- 26549975 TI - N-Acetyl-cysteine Protection Against Lead-Induced Oxidative Stress and Genotoxicity in Human Liver Carcinoma (HepG2) Cells. AB - The human liver carcinoma (HepG2) cells as well as other cell lines are particularly susceptible to oxidative damage, and it is therefore important to find agents that protect against this process. N-acetyl-cysteine (NAC) is the acetylated form of L-cysteine. It has an impressive list of protective effects including: antioxidant activity, decrease of the biologically effective dose of carcinogens, anti-inflammatory activity, immunological effects, inhibition of progression to malignancy and metastasis, and protection from the adverse effects of chemopreventive and chemotherapeutic agents. Previous studies in our laboratory have shown that lead nitrate induces cytotoxicity and oxidative stress to HepG2 cells in a dose-dependent manner. In this research, we hypothesized that the antioxidant, n-acetyl-l-cysteine attenuates oxidative stress and genotoxicity, and thereby provides cellular protection against lead toxicity. To this hypothesis, we performed the thiobarbituric acid test for lipid peroxidation and the microgel electrophoresis (comet) assay for genotoxicity. The results generated from the thiobarbituric acid test showed a significant reduction of lipid peroxidation by-product (malondialdehyde) in HepG2 cells co-exposed to NAC and lead nitrate compared to lead nitrate alone. Incubation of HepG2 cells with increasing concentrations of NAC decreased the amount of MDA formation progressively in lead nitrate-treated HepG2 cells. Data obtained from the comet assay indicated a strong dose-response relationship with regard to lead nitrate induced genotoxic damage in HepG2 cells. However, the addition of NAC in vitro showed a significant reduction (p < 0.05) in the comet tail length, percentage of DNA cleavage, comet tail moment, as well as comet tail arm respectively in cells co-treated with NAC and lead nitrate. Findings from these studies demonstrated that NAC inhibits malondialdehyde (MDA) production and genotoxicity in lead nitrate-treated HepG2 cells in a dose-dependent manner. Under this in vitro condition, NAC was found to be effective in reducing MDA formation, cellular injury, and genotoxic damage in HepG2 cells exposed to lead nitrate. PMID- 26549976 TI - The effects of common medications on volumetric phallometry. AB - Phallometry is a physiological measure of sexual response widely used for the assessment of paedophilia among sexual offenders. Although many medications decrease penile response sufficiently to interfere with sexual intercourse, it is unknown to what extent such medications might interfere with phallometric testing. In the current study, we utilized a naturalistic convenience sample of 1078 men who attended a clinic for assessment of sexual preferences, mostly related to sexual offence convictions. In the present analyses, we quantified the differences in penile response during phallometric assessment associated with taking a range of common medications. Participants on medication typically showed less penile output than participants not taking medications; however, differences were largely accounted for by age rather than by medication status. Though most medications were associated with decreases in penile responsivity during volumetric phallometric testing, such changes were small in absolute terms and appeared to be associated with ageing rather than with the medications themselves. PMID- 26549977 TI - Communication media and the dead: from the Stone Age to Facebook. AB - This article argues as follows: (i) The presence of the dead within a society depends in part on available communication technologies, specifically speech, stone, sculpture, writing, printing, photography and phonography (including the mass media), and most recently the internet. (ii) Each communication technology affords possibilities for the dead to construct and legitimate particular social groups and institutions - from the oral construction of kinship, to the megalithic legitimation of the territorial rights of chiefdoms, to the written word's construction of world religions and nations, to the photographic and phonographic construction of celebrity-based neo-tribalism, and to the digital reconstruction of family and friendship. (iii) Historically, concerns about the dead have on a number of occasions aided the development of new communication technologies - the causal connection between the two can go both ways. The argument is based primarily on critical synthesis of existing research literature. PMID- 26549978 TI - Generation 3 PAMAM dendrimer TAMRA conjugates containing precise dye/dendrimer ratios. AB - The synthesis, isolation, and characterization of generation 3 poly(amidoamine) (G3 PAMAM) dendrimer containing precise ratios of 5-carboxytetramethylrhodamine succinimidyl ester (TAMRA) dye (n = 1-3) per polymer particle are reported. Stochastic conjugation of TAMRA dye to the dendrimer was followed by separation into precise dye-polymer ratios using rp-HPLC. The isolated materials were characterized by rp-UPLC, MALDI-TOF-MS, and 1H NMR spectroscopy, UV-vis, and fluorescence spectroscopies. PMID- 26549979 TI - Enhancement effects of chelating agents on the degradation of tetrachloroethene in Fe(III) catalyzed percarbonate system. AB - The performance of Fe(III)-based catalyzed sodium percarbonate (SPC) for stimulating the oxidation of tetrachloroethene (PCE) for groundwater remediation applications was investigated. The chelating agents citric acid monohydrate (CIT), oxalic acid (OA), and Glutamic acid (Glu) significantly enhanced the degradation of PCE. Conversely, ethylenediaminetetraacetic acid (EDTA) had a negative impact on PCE degradation, which may due to its strong Fe chelation and HO* scavenging abilities. However, excessive SPC or chelating agent will retard PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO* radical oxidation in both the chelated and non-chelated systems, while O2*- also participated in the non-chelated system and the OA and Glu modified systems. According to the electron paramagnetic resonance (EPR) studies, the presence of HO* in the Fe(III)/SPC system was maintained much longer than that in the Fe(II)/SPC system. The results indicated that the addition of CIT, OA or Glu indeed enhanced the generation of HO* in the first 10 min and promoted degradation efficiency by increasing the amount of Fe(III) and maintaining the concentration of HO* radicals in solution. In conclusion, chelated Fe(III)-based catalyzed SPC oxidation is a promising method for the remediation of PCE contaminated groundwater. PMID- 26549980 TI - Synthesis of thiol derivatives of azobenzocrown ethers. The preliminary studies on recognition of alkali metal ions by gold nanoparticles functionalized with azobenzocrown and lipoic acid. AB - The article presents the synthesis of novel 13- and 16-membered azobenzocrown derivatives with peripheral thiol moieties and preliminary studies assessing their possible application in plasmonic sensors based on gold nanoparticles. The effect of the length of the chain connecting the macrocycle with the thiol group and the effect of the presence of the additional functional compound, i.e. lipoic acid, on the sensor response was analyzed. Colloidal gold nanoparticles modified with a 16-membered crown with a thiol group on oxyethylene (compound 12) or oxybutylene (compound 13) linker was found to have good properties, allowing for detection of potassium ions in aqueous solutions at concentrations 8-20 mM for bifunctionalized nanogold and 4-26 mM for less stable, colloidal gold modified only with thiol derivatives of azobenzocrowns. The response towards potassium cations of bifunctionalized nanogold modified with compound 13 was more stable in time than for the system incorporating compound 12. Compound 13, obtained with the highest yield among all presented thiol derivatives of azobenzocrowns, was selected for further, more detailed, studies. PMID- 26549984 TI - Occupational Consciousness. AB - Occupational consciousness refers to ongoing awareness of the dynamics of hegemony and recognition that dominant practices are sustained through what people do every day, with implications for personal and collective health. The emergence of the construct in post-apartheid South Africa signifies the country's ongoing struggle with negotiating long-standing dynamics of power that were laid down during colonialism, and maintained under black majority rule. Consciousness, a key component of the new terminology, is framed from post-colonial perspectives - notably work by Biko and Fanon - and grounded in the philosophy of liberation, in order to draw attention to continuing unequal intersubjective relations that play out through human occupation. The paper also draws important links between occupational consciousness and other related constructs, namely occupational possibilities, occupational choice, occupational apartheid, and collective occupation. The use of the term 'consciousness' in sociology, with related or different meanings, is also explored. Occupational consciousness is then advanced as a critical notion that frames everyday doing as a potentially liberating response to oppressive social structures. This paper advances theorizing as a scholarly practice in occupational science, and could potentially expand inter or transdisciplinary work for critical conceptualizations of human occupation. PMID- 26549983 TI - On the possibility of tree-level leptogenesis from Kalb-Ramond torsion background. AB - In this work we consider a phenomenological model for leptogenesis in the context of a Standard Model Extension with an axial-like background coupling to fermions that violates both Lorentz and CPT symmetries. The latter is motivated by a background geometry of the early Universe involving a particular kind of torsion, arising from the Kalb-Ramond antisymmetric tensor field which appears in the gravitational multiplet of string theory, although we do not restrict ourselves to this framework. It is shown that leptogenesis can occur even at tree level and with only one generation of right-handed heavy Majorana neutrinos, due to [Formula: see text] and CPT violation introduced by the background geometry. Important issues for the model, including (a) its compatibility with a conventional-like cosmology and (b) current-era phenomenology (characterised by very stringent bounds on the allowed amount of torsion) are pointed out, and potential ways of resolving them, within the framework of string-theory models, are discussed. PMID- 26549985 TI - Supervisors' pedagogical role at a clinical education ward - an ethnographic study. AB - BACKGROUND: Clinical practice is essential for health care students. The supervisor's role and how supervision should be organized are challenging issues for educators and clinicians. Clinical education wards have been established to meet these challenges and they are units with a pedagogical framework facilitating students' training in real clinical settings. Supervisors support students to link together theoretical and practical knowledge and skills. From students' perspectives, clinical education wards have shown potential to enhance students' learning. Thus there is a need for deeper understanding of supervisors' pedagogical role in this context. We explored supervisors' approaches to students' learning at a clinical education ward where students are encouraged to independently take care of patients. METHOD: An ethnographic approach was used to study encounters between patients, students and supervisors. The setting was a clinical education ward for nursing students at a university hospital. Ten observations with ten patients, 11 students and five supervisors were included in the study. After each observation, individual follow-up interviews with all participants and a group interview with supervisors were conducted. Data were analysed using an ethnographic approach. RESULTS: Supervisors' pedagogical role has to do with balancing patient care and student learning. The students were given independence, which created pedagogical challenges for the supervisors. They handled these challenges by collaborating as a supervisory team and taking different acts of supervision such as allowing students their independence, being there for students and by applying patient-centredness. CONCLUSION: The supervisors' pedagogical role was perceived as to facilitate students' learning as a team. Supervisors were both patient- and student-centred by making a nursing care plan for the patients and a learning plan for the students. The plans were guided by clinical and pedagogical guidelines, individually adjusted and followed up. PMID- 26549986 TI - The perseverance time of informal carers for people with dementia: results of a two-year longitudinal follow-up study. AB - BACKGROUND: Given the projected increase of people with dementia over the next few decades and the related demand for informal care, an important question for health policy makers is to what extent and for how long informal carers can be expected to provide care in a sustainable way. This study aimed to investigate the perseverance time of informal carers for people with dementia. METHODS: A 2 year longitudinal cohort study was conducted. Questionnaires were used to collect data about the care situation, the impact of caregiving on carers and their need for support, and the anticipated and realized perseverance time of informal carers for people with dementia living at home. The data were analysed using bivariate and multivariate analyses. RESULTS: Two hundred twenty-three carers for people with dementia were included in the study and 25 (11.2 %) dropped out during the follow-up. The results show that after 1 year, 74 (37.4 %) of 198 patients were still living at home, and after 2 years, 44 (22.2 %) patients were still living at home. The variables that were associated with this outcome were identified. When informal carers anticipated that their perseverance time would be less than 1 year, this was indicative of their actual perseverance time. CONCLUSIONS: Anticipated perseverance time provides a fair indication of the actual duration of informal care. It is most accurate when carers anticipate a limited rather than an unlimited perseverance time. Although further research is required to support these findings, the concept of perseverance time may be considered a useful additional instrument in health policy and clinical practice for monitoring carers' need for support and for planning the transition of care from home to a nursing home. PMID- 26549987 TI - Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. AB - Cyclooxygenase-2 (COX-2), an inducible form of the enzyme that catalyzes the first step in the synthesis of prostanoids, is associated with inflammatory diseases and carcinogenesis, which is suspected to promote angiogenesis and tissue invasion of tumors and resistance to apoptosis. Meanwhile, COX-2 contributes to immune evasion and resistance to cancer immunotherapy, which plays a crucial role in the innate and adaptive immune response. The activity of COX-2 PGE2-EP signal pathway can suppress Dendritic cells (DCs), natural killer (NK), T cells, type-1 immunity excluding type-2 immunity which promote tumor immune evasion. COX-2 and the prostaglandin cascade play important roles in the "inflammogenesis of cancer". In addition, COX-inhibitors can inhibit tumor immune evasion. Therefore, we can exert the COX-inhibitors to facilitate the patients to benefit from addition of COX-inhibitors to standard cytotoxic therapy. PMID- 26549988 TI - CFTR Knockdown induces proinflammatory changes in intestinal epithelial cells. AB - BACKGROUND: Hyperinflammation is a hallmark feature of cystic fibrosis (CF) airways. However, inflammation has also been documented systemically and, more recently, in extrapulmonary CF-affected tissues such as the pancreas and intestine. The pathogenesis of CF-related inflammation and more specifically the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in that respect are not entirely understood. We have tested the hypothesis that genetic depletion of CFTR will affect the inflammatory status of human intestinal epithelial cell lines. METHODS: CFTR expression was genetically depleted from Caco-2/15 and HT-29 cells using short hairpin RNA interference (shRNAi). Inflammatory conditions were induced by the addition of human recombinant tumor necrosis factor (TNF) or Interleukin-1beta (IL-1beta) for various periods of time. Gene expression, mRNA stability and secreted levels of interleukin (IL)-6, 8 and 10 were assessed. Analysis of pro- and anti-inflammatory signaling pathways including mitogen-activated protein kinases (p38, ERK 1/2 and JNK), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IkappaBalpha), and nuclear factor-kappa B (NF-kappaB) was also performed. Eosinophils were counted in the jejunal mucosa of Cftr-/- and Cftr+/+ mice. RESULTS: CFTR gene and protein knockdown caused a significant increase in basal secretion of IL-8 as well as in IL-1beta-induced secretion of IL-6 and -8. Release of the anti-inflammatory cytokine, IL-10, remained unaffected by CFTR depletion. The enhanced secretion of IL-8 stems in part from increased IL8 mRNA levels and greater activation of ERK1/2 MAPK, IkappaBalpha and NF-kappaB in the CFTR knockdown cells. By contrast, phosphorylation levels of p38 and JNK MAPK did not differ between control and knockdown cells. We also found a higher number of infiltrating eosinophils in the jejunal mucosa of Cftr -/- females, but not males, compared to Cftr +/+ mice, thus providing in vivo support to our in vitro findings. CONCLUSION: Collectively, these data underscore the role played by CFTR in regulating the intestinal inflammatory responses. Such findings lend support to the theory that CFTR exerts functions that may go beyond its role as a chloride channel whereby its disruption may prevent cells to optimally respond to exogenous or endogenous challenges. These observations are of particular interest to CF patients who were found to display alterations in their intestinal microbiota, thus predisposing them to pathogens that may elicit exaggerated inflammatory responses. PMID- 26549989 TI - What do women know about breast cancer prophylaxis and a healthy style of life? AB - AIM: The aim of the study was to determine the factors influencing women's knowledge concerning breast cancer prophylaxis and find out the sources of the knowledge. BACKGROUND: In the Greater Poland region, breast cancer has been the most frequently detected tumour for years. The percentage of breast cancer cases has increased by 31% in the last decade. MATERIALS AND METHODS: The study encompassed 337 women aged 40-59 who participated in the mammographic examinations. An original research tool was used which assessed the level of knowledge concerning breast cancer prophylaxis, the knowledge of health-oriented behaviour in this regard and the influence of the medical personnel on women's education. RESULTS: Age is a factor diversifying the knowledge of the breast self examination method. Doctors and nurses were rarely indicated as a source of knowledge concerning breast cancer prophylaxis. The subjects presented a high level of knowledge of the factors increasing the risk of developing cancer. CONCLUSIONS: A correlation between the level of education and the knowledge of one's own breast to a degree which enables a woman to detect even a slight change was observed. Vital findings also concern the sources of knowledge concerning breast cancer prophylaxis. The results of the studies indicated little informative support on the part of the medical personnel; therefore, one should call for supplementing training courses for doctors and nurses focusing on the issues of prophylaxis, including the method of breast self-examination. PMID- 26549991 TI - Pattern of radiotherapy care in Bulgaria. AB - The paper reveals the changing pattern of Bulgarian Radiotherapy (RT) care after the successful implementation of 15 projects for 100 million euro under the European Regional Development Fund in Operational Programme for Regional Development 2007-2013. The project enables a total one-step modernization of 14 Bulgarian RT Centres and creation of a new one. At the end of the Programme (mid 2015), 16 new Linacs and 2 modern cobalt machines will be available together with 11 virtual CT simulators, 5 CT simulators, 1 MRI and 1 PET CT for RT planning and all dosimetry facilities needed. Such a modernization has moved Bulgarian RT forward, with 2.7 MV units per one million of population (MV/mln.inh) in comparison with 0.9 MV/mln.inh in 2012. Guild of Bulgarian Radiotherapists includes 70 doctors, 46 physicists and 10 engineers, together with 118 RTTs and 114 nurses and they all have treated 16,447 patients in 2013. Major problems are inadequate reimbursement from the monopolistic Health Insurance Fund (900 euro for 3D conformal RT and 1500 euro for IMRT); fragmentation of RT care with 1-2 MV units per Centre; no payment for patient travel expenses; need for quick and profound education of 26% of doctors and 46% of physicists without RT license, along with continuous education for all others; and resource for 5000-9000 more patients to be treated yearly by RT in order to reach 45-50% from current service of 32%. After 15 years of struggle of RT experts, finally the pattern of Bulgarian RT care at 2014-2015 is approaching the level of modern European RT. PMID- 26549990 TI - Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature. AB - Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients. PMID- 26549992 TI - Influence of the type of imaging on the delineation process during the treatment planning. AB - AIM: The aim of this study was to compare the intra- and interobserver contouring variability for structures with density of organ at risk in two types of tomography: kilovoltage computed tomography (KVCT) versus megavoltage computed tomography (MVCT). The intra- and interobserver differences were examined on both types of tomography for structures which simulate human tissue or organs. MATERIALS AND METHODS: Six structures with density of the liver, bone, trachea, lung, soft tissue and muscle were created and used. For the measurements, the special water phantom with all structures was designed. To evaluate interobserver variability, five observers delineated the structures in both types of computed tomography (CT). RESULTS: Intraobserver variability was in the range of 1-14% and was the largest for the liver. The observers segmented larger volumes on MVCT compared with KVCT for the trachea (79.56 ccm vs.74.91 ccm), lung (87.61 vs. 82.50), soft tissue (154.24 vs. 145.47) and muscle (164.01 vs. 157.89). For the liver (98.13 vs. 99.38) and bone (51.86 vs. 67.97), the volume on MVCT was smaller than KVCT. The statistically significant differences between observers were observed for structures with density of the liver, bone and soft tissue on KVCT and for the liver, lung and soft tissue on MVCT. For the structures with density of the trachea and muscles, there were no significant differences for both types of tomography. CONCLUSIONS: During the contouring process the interobserver and intraobserver contouring uncertainty was larger on MVCT, especially for structures with HU near 80, compared with KVCT. PMID- 26549993 TI - Dosimetric impact of different multileaf collimators on prostate intensity modulated treatment planning. AB - AIM: The main purpose of this study is to perform a dosimetric comparison on target volumes and organs at risks (OARs) between prostate intensity modulated treatment plans (IMRT) optimized with different multileaf collimators (MLCs). BACKGROUND: The use of MLCs with a small leaf width in the IMRT optimization may improve conformity around the tumor target whilst reducing the dose to normal tissues. MATERIALS AND METHODS: Two linacs mounting MLCs with 5 and 10 mm leaf width, respectively, implemented in Pinnacle(3) treatment planning system were used for this work. Nineteen patients with prostate carcinoma undergoing a radiotherapy treatment were enrolled. Treatment planning with different setup arrangements (7 and 5 beams) were performed for each patient and each machine. Dose volume histograms (DVHs) cut-off points were used in the treatment planning comparison. RESULTS: Comparable planning target volume (PTV) coverage was obtained with 7- and 5-beam configuration (both with 5 and 10 mm MLC leaf-width). The comparison of bladder and rectum DVH cut-off points for the 5-beam arrangement shows that 52.6% of the plans optimized with a larger leaf-width did not satisfy at least one of the OARs' constraints. This percentage is reduced to 10.5% for the smaller leaf-width. If a 7-beam arrangement is used the value of 52.6% decreases to 21.1% while the value of 10.5% remains unchanged. CONCLUSION: MLCs collimators with different widths and number of leaves lead to a comparable prostate treatment planning if a proper adjustment is made of the number of gantry angles. PMID- 26549994 TI - Comparison of manual and inverse optimisation techniques in high dose rate intracavitary brachytherapy of cervical cancer: A dosimetric study. AB - AIMS AND OBJECTIVES: To compare dosimetrically the manual optimisation with IPSA using dose volume histograms (DVH) among patients treated for carcinoma of cervix with intracavitary brachytherapy. BACKGROUND: With the advent of advanced imaging modalities, there has been a shift from conventional X-ray based planning to three-dimensional planning. Manual optimisation is widely used across various institutions but it is time consuming and operator dependant. Inverse planning simulated annealing (IPSA) is now available in various brachytherapy planning systems. But there is a paucity of studies comparing manual optimisation and IPSA in treatment of carcinoma cervix with intracavitary brachytherapy and hence this study. MATERIALS AND METHODS: Fifteen consecutive patients treated between December 2013 and March 2014 with intracavitary brachytherapy for carcinoma of cervix were selected for this study. All patients were initially treated with external beam radiotherapy followed by intracavitary brachytherapy. The DVH was evaluated and compared between manually optimised plans and IPSA in the same set of patients. RESULTS: There was a significant improvement in the HRCTV coverage, mean V100 of 87.75% and 82.37% (p = 0.001) and conformity index 0.67 and 0.6 (p = 0.007) for plans generated using IPSA and manual optimisation, respectively. Homogeneity index and dose to the OARs remained similar between the two groups. CONCLUSION: The use of inverse planning in intracavitary brachytherapy of cervix has shown a significant improvement in the target volume coverage when compared with manual planning. PMID- 26549995 TI - SIMBOSPROST: Prevalence of metabolic syndrome and osteoporosis in prostate cancer patients treated with radiotherapy and androgen deprivation therapy: A multicentre, cross-sectional study. AB - AIM: To assess the prevalence of metabolic syndrome (MetS) and osteoporosis in patients with prostate cancer (PCa) treated with radical radiotherapy (RT) with or without androgen deprivation therapy (ADT). BACKGROUND: Worldwide, the prevalence of MetS is estimated to range from 20% to 25% of the adult population. However, prevalence rates are much higher in PCa patients (pts) who undergo ADT. MATERIALS AND METHODS: Multicentre cross-sectional study of 270 pts in Spain with PCa. Patients were divided into 3 groups based on the duration of ADT (6, 12-18, >=24 months) and compared to a control group without ADT. MetS was defined according to NCEP ATP III criteria. Osteoporosis was assessed by DEXA. RESULTS: A total of 270 pts, treated from November 2011 to October 2012, were included. Of these, 122 pts (47%) fulfilled the criteria for MetS. The median age of this group was significantly higher (71.3 vs. 69.38 years, p = 0.028). MetS prevalence was 50% in the control group. In pts who received ADT, prevalence was 44.8% after 6 months of ADT, 45.3% after 12-18 months, and 50% after >=24 months (pns). Most pts (168/270; 62%) underwent DEXA. Of those tested, 78 (46.4%) had osteopenia and only 11 (6.5%) had osteoporosis. CONCLUSIONS: The prevalence of MetS in pts with PCa treated with radical RT was higher (47%) than in the general population. However, there were no significant differences in the duration of ADT administration. The prevalence of osteoporosis was low. These findings suggest that the prevalence of MetS in PCa patients may be higher than previously reported. PMID- 26549996 TI - Pancreatic cancer and SBRT: A new potential option? AB - Local control remains a major issue for patients with unresectable, locally advanced pancreatic cancer (LAPC). The role of radiation therapy in the management of LAPC represents an area of some controversy. Stereotactic body radiotherapy is an emerging treatment option for LAPC as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation. The objective of this review is to present the rationale for stereotactic body radiotherapy in LAPC, as well as to discuss the potential limitations and caveats of the currently available studies. PMID- 26549997 TI - Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report. AB - AIM: To report a single-institution experience using postoperative pelvic Intensity Modulation Radiation Therapy (IMRT) using tomotherapy accelerators (TA) in postoperative endometrial cancer (EC) regarding ICRU 83 recommendations. BACKGROUND: IMRT in gynecological malignancies provides excellent dosimetric data, lower rates of adverse events and clinical data similar to historical series. MATERIAL AND METHODS: Seventy-six patients with EC were postoperatively treated with adjuvant IMRT using TA. The IMRT dose was 45 Gy for patients without positive lymph nodes and Type I histology and 50.4 Gy for patients with positive lymph nodes and/or type II histology. RESULTS: With a median follow-up of 29 months, the 12- and 24-month Overall Survival (OS) and Disease-Free Survival (DFS) were 96%, 93%, 87%, and 74%, respectively. Age of less than 60 years was associated with better OS (HR: 8.9; CI: 1.1-68) and DFS (HR: 3.5; CI: 1.2-10.2). Patients with Type II and Type I Grade III histology had a worse OS (HR: 3.3; CI: 1.1-11). Five women (6.6%) presented in-field local vaginal recurrence, 2 (2.6%) presented non-in-field vaginal recurrence, 4 (5.2%) presented pelvic node and distant recurrence and 11 (14.4%) presented only distant metastases. One patient stopped radiation treatment due to Grade III acute diarrhea. No Grade III late toxicity was observed. Planning Target Volume (PTV) coverage showed mean D2, D50, D95, and D98 of 51.64-46.23 Gy, 49.49-44.97 Gy, 48.62-43.96 Gy, and 48.47-43.58 Gy for patients who received 45 and 50.4 Gy, respectively. CONCLUSIONS: IMRT with TA in postoperative EC shows excellent conformity and homogeneity of PTV dose. Without Grade III late toxicity, data from this cohort demonstrated the utility of IMRT. PMID- 26549998 TI - Carcinoma of unknown primary in the head and neck: The evaluation of the effectiveness of (18)F-FDG-PET/CT, own experience. AB - AIM: The aim of the present study was to estimate the clinical effectiveness of (18)F-FDG-PET/CT in the detection of the primary tumor in patients with histologically proven squamous cell carcinoma cervical lymph nodes metastasis from an unknown primary. BACKGROUND: (18)F-fluorodeoxyglucose positron emission tomography combined with CT ((18)F-FDG-PET/CT) is believed to be very helpful in localization of primary tumor in CUP Syndrome patients. MATERIAL AND METHOD: 41 patients referred to Poznan Medical University Department of Head and Neck Surgery from January 2010 to December 2013 with CUP Syndrome were included in the study. All patients presented fine-needle biopsy proven squamous cell carcinoma metastasis of the upper-, or mid neck lymph nodes. The final results were obtained from the histopathologic reports of tissue samples from anatomical regions suspected for primary tumor, additional imaging exams as well as clinical follow-up data. RESULTS: The (18)F-FDG-PET/CT successfully detected primary tumor in 7 out of 41 patients (17%). In two more cases the primary tumor was indicated in the lung. 24 of 41 patients (58.5%) analyzed in our study remained without evidence of a primary tumor. In 4 cases (9.75%) we did not reveal any pathology within the localizations indicated by PET/CT on panendoscopy. In 4 cases we obtained histological confirmation of neoplasm on panendoscopy despite the negative results of PET/CT examinations. CONCLUSION: We may suppose a relatively high usefulness of (18)F-FDG-PET/CT in the diagnosis process of CUP Syndrome patients. High NPV may indicate patients with no symptoms of primary tumor, which allows to avoid extensive resection or extra imaging. PMID- 26549999 TI - Volumetric modulated arc therapy for synchronous bilateral whole breast irradiation - A case study. AB - PURPOSE: The treatment planning of bilateral breast irradiation (BBI) is a challenging task. The overlapping of tangential fields is usually unavoidable without compromising the target coverage. The purpose of this study was to investigate the technical feasibility and benefits of a single isocentre volumetric modulated arc therapy (VMAT) in BBI. METHODS AND MATERIALS: Two women with bilateral breast cancer were included in this case study. The first patient (Pat#1) underwent a bilateral breast-conserving surgery and sentinel lymph node biopsy. The second patient (Pat#2) underwent a bilateral ablation and axillary lymph node dissection. Planning target volumes (PTV) and organs at risk were delineated on CT images. VMAT plans were created with four (two for both sides, Pat#1) or two (one for each breast, Pat#2) separate VMAT fields. Subsequently, traditional tangential field plans were generated for each patient and the dosimetric parameters were compared. RESULTS: The treatment times of the patients with VMAT were less than 15 min with daily CBCT imaging. When compared to the standard tangential field technique, the VMAT plans improved the PTV dose coverage and dose homogeneity with improved sparing of lungs and heart. With traditional field arrangement, the overlapping of the tangential fields was inevitable without significantly compromising the target coverage, whereas with VMAT the hotspots were avoided. The patients were treated with the VMAT technique and no acute skin toxicity was observed with either of the patients. CONCLUSIONS: A single isocentre VMAT technique has been implemented clinically for BBI. With the VMAT techniques, the dose delivery was quick and the hotspots in the field overlapping areas were avoided. The PTV dose coverage was superior in VMAT plans when compared with conventional tangential technique plans. PMID- 26550000 TI - The Effects of Respondents' Consent to be Recorded on Interview Length and Data Quality in a National Panel Study. AB - Recording interviews is a key feature of quality control protocols for most survey organizations. We examine the effects on interview length and data quality of a new protocol adopted by a national panel study. The protocol recorded a randomly chosen one-third of all interviews digitally, although all respondents were asked for permission to record their interview, and interviewers were blind to whether or not interviews were recorded. We find that the recording software slowed the interview slightly. Interviewer knowledge that the interview may be recorded improved data quality, but this knowledge also increased the length of the interview. Interviewers with higher education and performance ratings were less reactive to the new recording protocol. Survey managers may face a trade-off between higher data quality and longer interviews when determining recording protocols. PMID- 26550001 TI - Web-Based Couple Interventions: Do They Have a Future? AB - To examine the current and potential future impact of formal and informal resources to enhance romantic relationships, 1,160 individuals were surveyed. When asked about resources previously utilized, participants reported that numerous forms of relationship help, including talking to a friend/coworker/family member, an individual therapist, and reading self-help materials had a larger impact than attending couple therapy. When asked about potential resources they would be likely to use in the future for relationship problems, participants indicated a strong preference for online self-help resources that included detailed feedback paired with a comprehensive, structured program. Implications for future development and dissemination are discussed. PMID- 26550002 TI - Knowledge gaps among public librarians seeking vaccination information: A qualitative study. AB - Public libraries have been called the "first responders" to the specialized health information needs of the general public. The challenges inherent in consumer health information (CHI) service are centered around the Patron, the Librarian, the Information Resources, and the Library itself. The pilot study involved interviews with nine individual library workers in eight public libraries in four library systems: the District of Columbia, Montgomery and Prince George's Counties in Maryland, and Fairfax County in Virginia. Library workers were asked about common consumer health information requests, the nature of their collections, and the role of public libraries in meeting these information needs. The subjects were also presented with a hypothetical scenario, and their responses suggest knowledge gaps. The findings point to the increasing necessity and importance of training and support for public librarians, as well as the importance of understanding where the medical knowledge gaps exist. Public librarians need to commit to formal evaluation of their skill sets and knowledge gaps, in order to identify areas to which libraries can devote limited resources. PMID- 26550003 TI - A robust and effective time-independent route to the calculation of Resonance Raman spectra of large molecules in condensed phases with the inclusion of Duschinsky, Herzberg-Teller, anharmonic, and environmental effects. AB - We present an effective time-independent implementation to model vibrational resonance Raman (RR) spectra of medium-large molecular systems with the inclusion of Franck-Condon (FC) and Herzberg-Teller (HT) effects and a full account of the possible differences between the harmonic potential energy surfaces of the ground and resonant electronic states. Thanks to a number of algorithmic improvements and very effective parallelization, the full computations of fundamentals, overtones, and combination bands can be routinely performed for large systems possibly involving more than two electronic states. In order to improve the accuracy of the results, an effective inclusion of the leading anharmonic effects is also possible, together with environmental contributions under different solvation regimes. Reduced-dimensionality approaches can further enlarge the range of applications of this new tool. Applications to imidazole, pyrene, and chlorophyll a1 in solution are reported, as well as comparisons with available experimental data. PMID- 26550004 TI - Stereo-electronic, vibrational, and environmental contributions to polarizabilities of large molecular systems: a feasible anharmonic protocol. AB - Reliable computations of linear and non-linear optical properties of molecular systems in condensed phases require a proper account of stereo-electronic, vibrational, and environmental effects. In the framework of density functional theory, these effects can be accurately introduced using second-order vibrational perturbation theory in conjunction with polarizable continuum models. We illustrate the combination of an anharmonic description of the ground-state potential energy surface with solvation effects treated with the polarizable continuum model (PCM) in the calculation of the electronic, zero-point, and pure vibrational polarizabilities of selected systems. The description of the solvation environment is enriched by taking into account the dynamical aspects of the solute-solvent interactions through the inclusion of both electronic and vibrational non-equilbrium effects, as well as the direct effect of the solvent on the electric field that generates the molecular response (local field effect). This treatment yields accurate results which can be directly compared with experimental findings without the need of empirical corrections. PMID- 26550005 TI - Teen Pregnancy Prevention Program Recommendations from Urban and Reservation Northern Plains American Indian Community Members. AB - Despite declines over the past few decades, the United States has one of the highest rates of teen pregnancy compared to other industrialized nations. American Indian youth have experienced higher rates of teen pregnancy compared to the overall population for decades. Although it's known that community and cultural adaptation enhance program effectiveness, few teen pregnancy prevention programs have published on recommendations for adapting these programs to address the specific needs of Northern Plains American Indian youth. We employed a mixed methods analysis of 24 focus groups and 20 interviews with a combined total of 185 urban and reservation-based American Indian youth and elders, local health care providers, and local school personnel to detail recommendations for the cultural adaptation, content, and implementation of a teen pregnancy prevention program specific to this population. Gender differences and urban /reservation site differences in the types of recommendations offered and the potential reasons for these differences are discussed. PMID- 26550006 TI - Trench Safety-Using a Qualitative Approach to Understand Barriers and Develop Strategies to Improve Trenching Practices. AB - Despite efforts to ensure workplace safety and health, injuries and fatalities related to trenching and excavation remain alarmingly high in the construction industry. Because properly installed trenching protective systems can potentially reduce the significant number of trenching fatalities, there is clearly a need to identify the barriers to the use of these systems and to develop strategies to ensure these systems are utilized consistently. The current study reports on the results of focus groups with construction workers and safety management personnel to better understand these barriers and to identify solutions. The results suggest several factors, from poor planning to pressures from experienced workers and supervisors, which present barriers to safe trenching practices. Based on the results, it is recommended that safety trainings incorporate unique messages for new workers, experienced workers and management in an effort to motivate each group to work safely as well as provide them with solutions to overcome the identified barriers. PMID- 26550007 TI - A novel nonparametric measure of explained variation for survival data with an easy graphical interpretation. AB - INTRODUCTION: For survival data the coefficient of determination cannot be used to describe how good a model fits to the data. Therefore, several measures of explained variation for survival data have been proposed in recent years. METHODS: We analyse an existing measure of explained variation with regard to minimisation aspects and demonstrate that these are not fulfilled for the measure. RESULTS: In analogy to the least squares method from linear regression analysis we develop a novel measure for categorical covariates which is based only on the Kaplan-Meier estimator. Hence, the novel measure is a completely nonparametric measure with an easy graphical interpretation. For the novel measure different weighting possibilities are available and a statistical test of significance can be performed. Eventually, we apply the novel measure and further measures of explained variation to a dataset comprising persons with a histopathological papillary thyroid carcinoma. CONCLUSION: We propose a novel measure of explained variation with a comprehensible derivation as well as a graphical interpretation, which may be used in further analyses with survival data. PMID- 26550008 TI - Can we resist another person's gaze? AB - Adaptive adjustments of strategies are needed to optimize behavior in a dynamic and uncertain world. A key function in implementing flexible behavior and exerting self-control is represented by the ability to stop the execution of an action when it is no longer appropriate for the environmental requests. Importantly, stimuli in our environment are not equally relevant and some are more valuable than others. One example is the gaze of other people, which is known to convey important social information about their direction of attention and their emotional and mental states. Indeed, gaze direction has a significant impact on the execution of voluntary saccades of an observer since it is capable of inducing in the observer an automatic gaze-following behavior: a phenomenon named social or joint attention. Nevertheless, people can exert volitional inhibitory control on saccadic eye movements during their planning. Little is known about the interaction between gaze direction signals and volitional inhibition of saccades. To fill this gap, we administered a countermanding task to 15 healthy participants in which they were asked to observe the eye region of a face with the eyes shut appearing at central fixation. In one condition, participants were required to suppress a saccade, that was previously instructed by a gaze shift toward one of two peripheral targets, when the eyes were suddenly shut down (social condition, SC). In a second condition, participants were asked to inhibit a saccade, that was previously instructed by a change in color of one of the two same targets, when a change of color of a central picture occurred (non-social condition, N-SC). We found that inhibitory control was more impaired in the SC, suggesting that actions initiated and stopped by social cues conveyed by the eyes are more difficult to withhold. This is probably due to the social value intrinsically linked to these cues and the many uses we make of them. PMID- 26550009 TI - The epidemiology of scorpion stings in tropical areas of Kermanshah province, Iran, during 2008 and 2009. AB - BACKGROUND: Scorpion stings are an acute health problem in tropical regions. Awareness of this problem is fundamental for establishing preventive interventions, thus prompting the present study to determine the scorpion-sting incidence in tropical areas of Kermanshah province during 2008 and 2009. METHODS: In a retrospective study, all records related to scorpion sting patients from the health centers of tropical areas of Kermanshah were studied by a census and checklist. Data were analyzed by the software SPSS-16 using descriptive and inferential tests. RESULTS: The incidence of scorpion stings was 334.37/100,000 inhabitants in 2008 and 339.07/100000 in 2009. Mean and standard deviation of age were 30.55 +/- 16.99. Scorpion stings were more common in rural areas (59.6 %) and occurred more often in summer (52.9 %). Nearly 48 % of bites were to patients' hands and 47.5 % of patients were injured between midnight and 6 a.m. While 92.9 % of patients had mild symptoms, scorpion antivenom was prescribed to 88.8 % of victims, 94.5 % of whom were discharged after outpatient treatment. The relationship between antivenom therapy and clinical symptoms was not significant. CONCLUSIONS: Due to the relatively high incidence of scorpion stings in tropical areas of Kermanshah, it is recommended that the inhabitants be educated through the mass media about how to prevent the stings and apply preliminary treatment. PMID- 26550010 TI - Two Different Points of View through Artificial Intelligence and Vector Autoregressive Models for Ex Post and Ex Ante Forecasting. AB - The ANN method has been applied by means of multilayered feedforward neural networks (MLFNs) by using different macroeconomic variables such as the exchange rate of USD/TRY, gold prices, and the Borsa Istanbul (BIST) 100 index based on monthly data over the period of January 2000 and September 2014 for Turkey. Vector autoregressive (VAR) method has also been applied with the same variables for the same period of time. In this study, different from other studies conducted up to the present, ENCOG machine learning framework has been used along with JAVA programming language in order to constitute the ANN. The training of network has been done by resilient propagation method. The ex post and ex ante estimates obtained by the ANN method have been compared with the results obtained by the econometric forecasting method of VAR. Strikingly, our findings based on the ANN method reveal that there is a possibility of financial distress or a financial crisis in Turkey starting from October 2017. The results which were obtained with the method of VAR also support the results of ANN method. Additionally, our results indicate that the ANN approach has more superior prediction performance than the VAR method. PMID- 26550012 TI - The Role of Interferon in the Management of BCG Refractory Nonmuscle Invasive Bladder Cancer. AB - Background. Thirty to forty percent of patients with high grade nonmuscle invasive bladder cancer (NMIBC) fail to respond to intravesical therapy with bacillus Calmette-Guerin (BCG). Interferon-alpha2B plus BCG has been shown to be effective in a subset of patients with NMIBC BCG refractory disease. Here we present a contemporary series on the effectiveness and safety of intravesical BCG plus interferon-alpha2B therapy in patients with BCG refractory NMIBC. Methods. From January of 2005 to April of 2014 we retrospectively found 44 patients who underwent induction with combination IFN/BCG for the management of BCG refractory NMIBC. A chart review was performed to assess initial pathological stage/grade, pathological stage/grade at the time of induction, time to IFN/BCG failure, pathological stage/grade at failure, postfailure therapy, and current disease state. Results. Of the 44 patients who met criteria for the analysis. High risk disease was found in 88.6% of patients at induction. The 12-month and 24-month recurrence-free survival were 38.6% and 18.2%, respectively. 25 (56.8%) ultimately had disease recurrence. Radical cystectomy was performed in 16 (36.4%) patients. Conclusion. Combination BCG plus interferon-alpha2B remains a reasonably safe alternative treatment for select patients with BCG refractory disease prior to proceeding to radical cystectomy. PMID- 26550013 TI - Evaluating the Efficacy of Treatment with a GnRH Analogue in Patients with Central Precocious Puberty. AB - Objective. GnRH analogues (GnRHa) are used in the treatment of central precocious puberty (CPP). The purpose of this study was to evaluate the efficacy of treatment with a GnRHa (leuprolide acetate) in patients with CPP. Subjects and Methods. A total of 62 female child patients who had been diagnosed with CPP, rapidly progressive precocious puberty (RP-PP), or advanced puberty (AP) and started on GnRHa treatment (leuprolide acetate, Lucrin depot, 3.75 mg once every 28 days) were included in the study. The efficacy of treatment was evaluated with anthropometric data obtained, progression of pubertal symptoms observed, as well as GnRHa tests, and, when necessary, intravenous GnRH tests carried out in physical examinations that were performed once every 3 months. Results. In the current study, treatment of early/advanced puberty at a dose of 3.75 mg once every 28 days resulted in the suppression of the HHG axis in 85.5% of the patients. Conclusion. The findings of this study revealed that a high starting dose of leuprolide acetate may not be necessary in every patient for the treatment of CPP. Starting at a dose of 3.75 mg once every 28 days and increasing it with regard to findings in follow-ups would be a better approach. PMID- 26550011 TI - Exploring the Physiological Link between Psoriasis and Mood Disorders. AB - Psoriasis is a chronic, immune-mediated skin condition with a high rate of psychiatric comorbidity, which often goes unrecognized. Beyond the negative consequences of mood disorders like depression and anxiety on patient quality of life, evidence suggests that these conditions can worsen the severity of psoriatic disease. The mechanisms behind this relationship are not entirely understood, but inflammation seems to be a key feature linking psoriasis with mood disorders, and physiologic modulators of this inflammation, including the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, demonstrate changes with psychopathology that may be contributory. Cyclical disruptions in the secretion of the sleep hormone, melatonin, are also observed in both depression and psoriasis, and with well-recognized anti-inflammatory and antioxidant activity, this aberration may represent a shared contributor to both conditions as well as common comorbidities like diabetes and cardiovascular disease. While understanding the complexities of the biological mechanisms at play will be key in optimizing the management of patients with comorbid psoriasis and depression/anxiety, one thing is certain: recognition of psychiatric comorbidity is an imperative first step in effectively treating these patients as a whole. Evidence that improvement in mood decreases psoriasis severity underscores how psychological awareness can be critical to clinicians in their practice. PMID- 26550014 TI - The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance. AB - Background. The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance. Methods. 42 obese female patients who had gigantomastia were operated on. We recorded patients' demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference. Results. Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively. Conclusion. Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk. PMID- 26550015 TI - The Iron Status of Sickle Cell Anaemia Patients in Ilorin, North Central Nigeria. AB - Objectives. Sickle cell anaemia (SCA) is one of the commonest genetic disorders in the world. It is characterized by anaemia, periodic attacks of thrombotic pain, and chronic systemic organ damage. Recent studies have suggested that individuals with SCA especially from developing countries are more likely to be iron deficient rather than have iron overload. The study aims to determine the iron status of SCA patients in Ilorin, Nigeria. Methods. A cross-sectional study of 45 SCA patients in steady state and 45 non-SCA controls was undertaken. FBC, blood film, sFC, sTfR, and sTfR/log sFC index were done on all subjects. Results. The mean patients' serum ferritin (589.33 +/- 427.61 ng/mL) was significantly higher than the mean serum ferritin of the controls (184.53 +/- 119.74 ng/mL). The mean serum transferrin receptor of the patients (4.24 +/- 0.17 MUg/mL) was higher than that of the controls (3.96 +/- 0.17 MUg/mL) (p = 0.290). The mean serum transferrin receptor (sTfR)/log serum ferritin index of the patients (1.65 +/- 0.27 MUg/mL) was significantly lower than that of the control (1.82 +/- 0.18 MUg/mL) (p = 0.031). Conclusion. Iron deficiency is uncommon in SCA patients and periodic monitoring of the haematological, biochemical, and clinical features for iron status in SCA patients is advised. PMID- 26550016 TI - Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion. AB - Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine 10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity. PMID- 26550017 TI - Ongoing Pregnancies following Cosmetic Micromanipulation of Preimplantation Embryos in Patients with Implantation Failure. AB - Cosmetic micromanipulation is defined as fragment and coarse granulation removal from preimplantation embryos. We report two cases of pregnancies in patients with implantation failure following cosmetic micromanipulation. PMID- 26550018 TI - Arctigenin from Fructus Arctii (Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers. AB - Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco 2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function. PMID- 26550020 TI - Moxibustion Reduces Ovarian Granulosa Cell Apoptosis Associated with Perimenopause in a Natural Aging Rat Model. AB - In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell (GC) apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM) modulated the circulating levels of estradiol and follicle stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause. PMID- 26550019 TI - Plumbagin Ameliorates CCl 4 -Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway. AB - Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 MUM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of alpha-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells. PMID- 26550021 TI - An Improved PID Algorithm Based on Insulin-on-Board Estimate for Blood Glucose Control with Type 1 Diabetes. AB - Automated closed-loop insulin infusion therapy has been studied for many years. In closed-loop system, the control algorithm is the key technique of precise insulin infusion. The control algorithm needs to be designed and validated. In this paper, an improved PID algorithm based on insulin-on-board estimate is proposed and computer simulations are done using a combinational mathematical model of the dynamics of blood glucose-insulin regulation in the blood system. The simulation results demonstrate that the improved PID algorithm can perform well in different carbohydrate ingestion and different insulin sensitivity situations. Compared with the traditional PID algorithm, the control performance is improved obviously and hypoglycemia can be avoided. To verify the effectiveness of the proposed control algorithm, in silico testing is done using the UVa/Padova virtual patient software. PMID- 26550022 TI - Nonlinear Time Domain Relation between Respiratory Phase and Timing of the First Heart Sound. AB - The previous studies on respiratory physiology have indicated that inspiration and expiration have opposite effects on heart hemodynamics. The basic reason why these opposite hemodynamic changes cause regular timing variations in heart sounds is the heart sound generation mechanism that the acoustic vibration is triggered by heart hemodynamics. It is observed that the timing of the first heart sound has nonlinear relation with respiratory phase; that is, the timing delay with respect to the R-wave increases with inspiration and oppositely decreases with expiration. This paper models the nonlinear relation by a Hammerstein-Wiener model where the respiratory phase is the input and the timing is the output. The parameter estimation for the model is presented. The model is tested by the data collected from 12 healthy subjects in terms of mean square error and model fitness. The results show that the model can approximate the nonlinear relation very well. The average square error and the average fitness for all the subjects are about 0.01 and 0.94, respectively. The timing of the first heart sound related to respiratory phase can be accurately predicted by the model. The model has potential applications in fast and easy monitoring of respiration and heart hemodynamics induced by respiration. PMID- 26550023 TI - Enhanced Z-LDA for Small Sample Size Training in Brain-Computer Interface Systems. AB - BACKGROUND: Usually the training set of online brain-computer interface (BCI) experiment is small. For the small training set, it lacks enough information to deeply train the classifier, resulting in the poor classification performance during online testing. METHODS: In this paper, on the basis of Z-LDA, we further calculate the classification probability of Z-LDA and then use it to select the reliable samples from the testing set to enlarge the training set, aiming to mine the additional information from testing set to adjust the biased classification boundary obtained from the small training set. The proposed approach is an extension of previous Z-LDA and is named enhanced Z-LDA (EZ-LDA). RESULTS: We evaluated the classification performance of LDA, Z-LDA, and EZ-LDA on simulation and real BCI datasets with different sizes of training samples, and classification results showed EZ-LDA achieved the best classification performance. CONCLUSIONS: EZ-LDA is promising to deal with the small sample size training problem usually existing in online BCI system. PMID- 26550024 TI - A Model of Regularization Parameter Determination in Low-Dose X-Ray CT Reconstruction Based on Dictionary Learning. AB - In recent years, X-ray computed tomography (CT) is becoming widely used to reveal patient's anatomical information. However, the side effect of radiation, relating to genetic or cancerous diseases, has caused great public concern. The problem is how to minimize radiation dose significantly while maintaining image quality. As a practical application of compressed sensing theory, one category of methods takes total variation (TV) minimization as the sparse constraint, which makes it possible and effective to get a reconstruction image of high quality in the undersampling situation. On the other hand, a preliminary attempt of low-dose CT reconstruction based on dictionary learning seems to be another effective choice. But some critical parameters, such as the regularization parameter, cannot be determined by detecting datasets. In this paper, we propose a reweighted objective function that contributes to a numerical calculation model of the regularization parameter. A number of experiments demonstrate that this strategy performs well with better reconstruction images and saving of a large amount of time. PMID- 26550025 TI - Metallothionein ameliorates burn sepsis partly via activation of Akt signaling pathway in mice: a randomized animal study. AB - INTRODUCTION: Metallothioneins (MTs) are a family of cysteine-rich and low molecular-weight proteins that can regulate metal metabolism and act as antioxidants. Recent studies showed that MTs played a protective role in excessive inflammation and sepsis. However, the role of MTs in burn sepsis remains unclear. This study is designed to investigate the role of MTs in burn sepsis in an experimental mouse model. METHODS: MT-I/II knockout (-/-) mice on a C57BL/6 background and their wild-type (WT) littermates were randomly divided into sham burn, burn, burn sepsis, Zn treated and Zn-MT-2 treated groups. Levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was detected by spectrophotometry. In in vitro study, exogenous MT was added to macrophages that stimulated with serum from burn sepsis mice with or without Akt inhibitor LY294002. The IL-1 beta and IL-6 mRNA expression were detected by quantitative real-time polymerase chain reaction. The levels of Akt expression were determined by western blot. RESULTS: Burn sepsis induced significantly elevated levels of inflammatory cytokines in serum and increased inflammatory infiltration in the liver and lung. These effects were more prominent in MT (-/-) mice than in WT mice. Furthermore, exogenous MT-2 inhibited these elevated inflammatory response in both WT and MT ( /-) mice. MT-2 up-regulated Akt phosphorylation and abrogated the increase of IL 1beta and IL-6 mRNA expression from macrophages that stimulated with burn sepsis serum. These effects of MT-2 were abolished in the presence of LY294002. CONCLUSION: MT-2 ameliorates burn sepsis by attenuating inflammatory response and diminishing inflammatory organ damage, which is at least partly mediated by activation of Akt signaling pathway. PMID- 26550026 TI - The impact of early surgical intervention in free intestinal perforation: a time to-intervention pilot study. AB - PURPOSES: An abdominal inflammatory focus is the second most often source of sepsis with a high risk of death in surgical intensive care units. By establishing evidence-based bundled strategies the surviving sepsis campaign provided an optimized rapid and continuous treatment of these emergency patients. Hereby the hospital mortality decreased from 35 to 30 %. Sepsis treatment is based on three major therapeutic elements: surgical treatment (source control), antiinfective treatment, and supportive care. The international guidelines of the surviving sepsis campaign were updated recently and recommend rapid diagnosis of the infection and source control within the first 12 h after the diagnosis (grade 1c). Interestingly this recommendation is mainly based on studies on soft tissue infections. METHODS: In this retrospective analysis 76 septic patients with an intraabdominal inflammatory focus were included. All patients underwent surgery at different time-points after diagnosis. RESULTS: With 80 % patients of the early intervention group had an improved overall survival (vs. 73 % in the late intervention group). CONCLUSIONS: Literature on the time dependency of early source control is rare and in part contradicting. Results of this pilot study reveal that immediate surgical intervention might be of advantage for septic emergency patients. Further multi-center approaches will be necessary to evaluate, whether the TTI has any impact on the outcome of septic patients with intestinal perforation. PMID- 26550027 TI - Erratum to: Psychosomatic complaints and sense of coherence among adolescents in a county in Sweden: a cross-sectional school survey. PMID- 26550028 TI - Stress-induced cortisol is associated with generation of non-negative interpretations during cognitive reappraisal. AB - BACKGROUND: Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes. METHODS: A total of 36 participants (Mean age = 21.3 years, SD = 1.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level. RESULTS: Participants were allocated post-hoc to either a responder (n = 19) or non-responder group (n = 17) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled. CONCLUSIONS: Although baseline cortisol and sex may have impacted the results, the results suggest that stress-induced cortisol is associated with difficulty in non-negative interpretation generation during the cognitive reappraisal process. PMID- 26550029 TI - Identification of structural alerts for liver and kidney toxicity using repeated dose toxicity data. AB - BACKGROUND: The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed. RESULTS: We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP). CONCLUSIONS: It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances. PMID- 26550030 TI - What is "colonial" about medieval colonial medicine? Iberian health in global context. AB - Colonial medicine is a thriving field of study in the history of nineteenth- and twentieth-century medicine. Medicine can be used as a lens to view colonialism in action and as a way to critique colonialism. This article argues that key debates and ideas from that modern field can fruitfully be applied to the Middle Ages, especially for the early empires of Spain and Portugal (mid-fourteenth to mid sixteenth centuries). The article identifies key modern debates, explores approaches to colonization and colonialism in the Middle Ages and discusses how medieval and modern medicine and healthcare could be compared using colonial and postcolonial discourses. The article ends with three case studies of healthcare encounters in Madeira, Granada and Hispaniola at the end of the fifteenth century. PMID- 26550031 TI - Lipid production in association of filamentous fungi with genetically modified cyanobacterial cells. AB - BACKGROUND: Numerous strategies have evolved recently for the generation of genetically modified or synthetic microalgae and cyanobacteria designed for production of ethanol, biodiesel and other fuels. In spite of their obvious attractiveness there are still a number of challenges that can affect their economic viability: the high costs associated with (1) harvesting, which can account for up to 50 % of the total biofuel's cost, (2) nutrients supply and (3) oil extraction. Fungal-assisted bio-flocculation of microalgae is gaining increasing attention due to its high efficiency, no need for added chemicals and low energy inputs. The implementation of renewable alternative carbon, nitrogen and phosphorus sources from agricultural wastes and wastewaters for growing algae and fungi makes this strategy economically attractive. RESULTS: This work demonstrates that the filamentous fungi, Aspergillus fumigatus can efficiently flocculate the unicellular cyanobacteria Synechocystis PCC 6803 and its genetically modified derivatives that have been altered to enable secretion of free fatty acids into growth media. Secreted free fatty acids are potentially used by fungal cells as a carbon source for growth and ex-novo production of lipids. For most of genetically modified strains the total lipid yields extracted from the fungal-cyanobacterial pellets were found to be higher than additive yields of lipids and total free fatty acids produced by fungal and Synechocystis components when grown in mono-cultures. The synergistic effect observed in fungal Synechocystis associations was also found in bioremediation rates when animal husbandry wastewater was used an alternative source of nitrogen and phosphorus. CONCLUSION: Fungal assisted flocculation can complement and assist in large scale biofuel production from wild-type and genetically modified Synechocystis PCC 6803 strains by (1) efficient harvesting of cyanobacterial cells and (2) producing of high yields of lipids accumulated in fungal-cyanobacterial pellets. PMID- 26550032 TI - First insights on the retroelement Rex1 in the cytogenetics of frogs. AB - BACKGROUND: While some transposable elements (TEs) have been found in the sequenced genomes of frog species, detailed studies of these elements have been lacking. In this work, we investigated the occurrence of the Rex1 element, which is widespread in fish, in anurans of the genus Physalaemus. We isolated and characterized the reverse transcriptase (RT)-coding sequences of Rex1 elements of five species of this genus. RESULTS: The amino acid sequences deduced from the nucleotide sequences of the isolated fragments allowed us to unambiguously identify regions corresponding to domains 3-7 of RT. Some of the nucleotide sequences isolated from Physlaemus ephippifer and P. albonotatus had internal deletions, suggesting that these fragments are likely not active TEs, despite being derived from a Rex1 element. When hybridized with metaphase chromosomes, Rex1 probes were revealed at the pericentromeric heterochromatic region of the short arm of chromosome 3 of the P. ephippifer karyotype. Neither other heterochromatin sites of the P. ephippifer karyotype nor any chromosomal regions of the karyotypes of P. albonotatus, P. spiniger and P. albifrons were detected with these probes. CONCLUSIONS: Rex1 elements were found in the genomes of five species of Physalaemus but clustered in only the P. ephippifer karyotype, in contrast to observations in some species of fish, where large chromosomal sites with Rex1 elements are typically present. PMID- 26550033 TI - Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP: a new familial case. AB - BACKGROUND: Thrombocytopenia-absent radius syndrome (TAR; MIM 274000) is a rare autosomal recessive disorder combining specific skeletal abnormalities with a reduced platelet count. TAR syndrome has been associated with the compound inheritance of an interstitial microdeletion in 1q21.1 and a low frequency noncoding RBM8A SNP. RESULTS: Here, we report on a patient with scapulo-humeral hypoplasia, bilateral radio-ulnar agenesis with intact thumbs, bilateral proximal positioning of the first metacarpal, bilateral fifth finger clinodactyly, bilateral radial deviation of the hands, and thrombocytopenia. Molecular studies showed compound heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant in hemizygous state, inherited from the father and the mother, respectively. A second aborted fetus presented TAR features and 1q21.1 microdeletion. DISCUSSION: The complex inheritance pattern resulted in reduced expression of Y14, the protein encoded by RBM8A, and a component of the core exon junction complex (EJC) in platelets. Further studies are needed to explain how Y14 insufficiency and subsequent defects of the EJC could cause the skeletal, haematological and additional features of TAR syndrome. In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome. CONCLUSION: In this study, we discuss other factors that could influence the overall phenotype of patients affected by TAR syndrome. PMID- 26550035 TI - Editorial. PMID- 26550034 TI - Tip60 complex binds to active Pol II promoters and a subset of enhancers and co regulates the c-Myc network in mouse embryonic stem cells. AB - BACKGROUND: Tip60 (KAT5) is the histone acetyltransferase (HAT) of the mammalian Tip60/NuA4 complex. While Tip60 is important for early mouse development and mouse embryonic stem cell (mESC) pluripotency, the function of Tip60 as reflected in a genome-wide context is not yet well understood. RESULTS: Gel filtration of nuclear mESCs extracts indicate incorporation of Tip60 into large molecular complexes and exclude the existence of large quantities of "free" Tip60 within the nuclei of ESCs. Thus, monitoring of Tip60 binding to the genome should reflect the behaviour of Tip60-containing complexes. The genome-wide mapping of Tip60 binding in mESCs by chromatin immunoprecipitation (ChIP) coupled with high throughput sequencing (ChIP-seq) shows that the Tip60 complex is present at promoter regions of predominantly active genes that are bound by RNA polymerase II (Pol II) and contain the H3K4me3 histone mark. The coactivator HAT complexes, Tip60- and Mof (KAT8)-containing (NSL and MSL), show a global overlap at promoters, whereas distinct binding profiles at enhancers suggest different regulatory functions of each essential HAT complex. Interestingly, Tip60 enrichment peaks at about 200 bp downstream of the transcription start sites suggesting a function for the Tip60 complexes in addition to histone acetylation. The comparison of genome-wide binding profiles of Tip60 and c-Myc, a somatic cell reprogramming factor that binds predominantly to active genes in mESCs, demonstrate that Tip60 and c-Myc co-bind at 50-60 % of their binding sites. We also show that the Tip60 complex binds to a subset of bivalent developmental genes and defines a set of mESC-specific enhancer as well as super-enhancer regions. CONCLUSIONS: Our study suggests that the Tip60 complex functions as a global transcriptional co-activator at most active Pol II promoters, co-regulates the ESC-specific c-Myc network, important for ESC self-renewal and cell metabolism and acts at a subset of active distal regulatory elements, or super enhancers, in mESCs. PMID- 26550036 TI - Community-oriented integrated care and health promotion - views from the street. AB - On the 1st and 2nd May 2015, participants at the RCGP London City Health Conference debated practical ways to achieve integrated care at community level. In five connected workshops, participants reviewed current work and identified ways to overcome some of the problems that had become apparent. In this paper, we summarise the conclusions of each workshop, and provide an overall comment. There are layers of complexity in community-oriented integrated care that are not apparent at first sight. The difficult thing is not persuading people that it matters, but finding ways to do it that are practical and sustainable. The dynamic and complex nature of the territory is bewildering. The expectation of silo-operating and linear thinking, and the language and models that encourage it, pervade health and social care. Comprehensive integration is possible, but the theory and practice are unfamiliar to many. Images, theories and models are needed to help people from all parts of the system to see big pictures and focused detail at the same time and oscillate between them to envision-integrated whole systems. Infrastructure needs to enable this, with coordination hubs, locality-based multidisciplinary meetings and cycles of inter-organisational improvement to nurture relationships across organisational boundaries. PMID- 26550037 TI - Singling out the double effect - sexual health advice and contraception are ethically distinct. AB - This article is a response to an article previously published in LJPC, which employed the doctrine of double effect to explain the Gillick judgement and exculpate health care workers who provide contraceptives and sexual health advice to under-16s. In this analysis, the two acts: provision of contraceptives and provision of sexual health advice are examined separately against the four criteria of the doctrine of double effect. In conclusion, whilst sexual health advice provision fits into the doctrine reasonably well, in the case of contraceptive provision, the validity of the doctrine of double effect is more doubtful. PMID- 26550038 TI - Singling out the double effect - some further comment. AB - We comment on a paper published in the same issue of the London Journal of Primary Care. We applaud Bow's engagement with the ethical issues in a previous LJPC paper but argue that further work is needed to establish the everyday moral concerns of health care workers in primary care. We also suggest that the ethical distinction between advice and medication and devices may be artificial if both have an effect on a patient. PMID- 26550039 TI - Steroid-induced hyperglycaemia in primary care. PMID- 26550040 TI - Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients. AB - BACKGROUND: Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays. FINDINGS: Seventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells. CONCLUSION: CD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This case-control study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases. PMID- 26550042 TI - Innovative Physics and Engineering Research in Nuclear Medicine and Molecular Imaging: A Message from the Associate Editor. PMID- 26550043 TI - PET Radioligands for Imaging of Tau Pathology: Current Status. AB - The incidence of Alzheimer's disease (AD), a progressive neurodegenerative disorder, continues to soar with the rapid growth of the elderly population, thus creating an enormous social and economic burden. Although disease-modifying drugs to treat AD are not yet available, several candidate drugs are in clinical trials. Most of these drugs are expected to be effective at the early stages of the disease, and therefore the early and accurate diagnosis of AD will be a critical factor in efforts to improve the prognosis of patients with AD. This review focuses on lead radioligands developed to date and their preclinical data in order to facilitate the development of tau-specific positron emission tomography radioligands that are of great interest to the scientific community. PMID- 26550041 TI - Real-time monitoring efficiency and toxicity of chemotherapy in patients with advanced lung cancer. AB - BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST) guideline and Common Terminology Criteria for Adverse Events (CTCAE) criteria are used to assess chemotherapy efficiency and toxicity in patients with advanced lung cancer. However, no real-time, synchronous indicators that can evaluate chemotherapy outcomes are available. We wanted to evaluate tumor response and toxicity in advanced lung cancer chemotherapy by using a novel synchronous strategy. RESULTS: We enrolled 316 patients with advanced lung cancer who were treated with cisplatin-based therapy and followed up them for 3 years. Plasma was obtained before and after every chemotherapy cycle. We quantitative assayed total plasma DNA and methylation of the APC/RASSF1A genes. Four parameters were assessed: methylation level before chemotherapy (meth0 h), methylation level 24 h after chemotherapy (meth24 h), total plasma DNA concentration before chemotherapy (DNA0 h), and total plasma DNA concentration 24 h after chemotherapy (DNA24 h). When meth24 h > meth0 h of at least one gene was used to predict tumor response, the correct prediction rate was 82.4 %. Additionally, patients for whom DNA24 h/DNA0 h <= 2 had mild toxicities. Therefore, meth24 h > meth0 h and DNA24 h/DNA0 h <= 2 were defined as criteria for better tumor response and fewer adverse events with a high correct prediction rate (84.7 %). CONCLUSIONS: Quantitative analysis of total plasma DNA and plasma APC/RASSF1A methylation provide a real time synchronous rapid monitoring indicator for therapeutic outcomes of advanced lung cancer, which could be a reference or supplementary guidelines in evaluating chemotherapy effects. PMID- 26550044 TI - Click Reaction: An Applicable Radiolabeling Method for Molecular Imaging. AB - In recent years, the click reaction has found rapidly growing applications in the field of radiochemistry, ranging from a practical labeling method to molecular imaging of biomacromolecules. This present review details the development of highly reliable, powerful and selective click chemistry reactions for the rapid synthesis of new radiotracers for molecular imaging. PMID- 26550045 TI - Analysis of Clinical Factors for the Determination of Optimal Serum Level of Thyrotropin After Recombinant Human Thyroid-Stimulating Hormone Administration. AB - PURPOSE: To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH. METHODS: We retrospectively analyzed 276 patients with differentiated thyroid cancer (DTC), post-thyroidectomy and remnant ablation. Pearson's correlation coefficient test was used to evaluate the correlation between serum levels of TSH after rhTSH stimulation and various clinical factors, including age, sex, height, weight, body mass index (BMI), body surface area (BSA), serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR). Linear regression analysis was used to determine the predictors of the degree of increase in serum TSH level after rhTSH stimulation. RESULTS: After the rhTSH injections, all subjects achieved TSH levels of >30 MUU/mL, with a mean of 203.8 +/- 83.4 MUU/mL. On univariate analysis, age (r = 0.255) and serum creatinine (r = 0.169) level were positive predictors for higher levels of serum TSH after rhTSH stimulation, while weight (r = -0.239), BMI (r = -0.223), BSA (r = -0.217), and estimated GFR (r = -0.199) were negative predictors. Multiple linear regression analysis revealed that serum creatinine was the most powerful independent predictor for serum levels of TSH, followed by age, BSA, and BMI. CONCLUSIONS: An increment in serum TSH after rhTSH stimulation was significantly affected by age, BSA, BMI, and creatinine, with creatinine being the most powerful predictor. By understanding the difference in the increased levels of TSH in various subjects, their dose of rhTSH can be adjusted during scheduling for radioiodine ablation, or during follow-up (recurrence surveillance) after surgery and ablation. PMID- 26550047 TI - Comparison of Diagnostic Sensitivity and Quantitative Indices Between (68)Ga DOTATOC PET/CT and (111)In-Pentetreotide SPECT/CT in Neuroendocrine Tumors: a Preliminary Report. AB - PURPOSE: In-pentetreotide has been used for neuroendocrine tumors expressing somatostatin receptors. Recently, (68)Ga-DOTATOC PET has been used with the advantage of high image quality. In this study, we compared quantitative indices between (111)In-pentetreotide SPECT/CT and (68)Ga-DOTATOC PET/CT. METHODS: Thirteen patients diagnosed with neuroendocrine tumors were prospectively recruited. Patients underwent (111)In-pentetreotide scans with SPECT/CT and (68)Ga-DOTATOC PET/CT before treatment. The number and location of lesions were analyzed on both imaging techniques to compare lesion detectability. Additionally, the maximal uptake count of each lesion and mean uptake count of the lungs were measured on both imagings, and target-to-normal lung ratios (TNR) were calculated as quantitative indices. RESULTS: Among 13 patients, 10 exhibited lesions with increased uptake on (111)In-pentetreotide SPECT/CT and/or (68)Ga DOTATOC PET/CT. Scans with SPECT/CT detected 19 lesions, all of which were also detected on PET/CT. Moreover, 16 additional lesions were detected on PET/CT (6 in the liver, 9 in the pancreas and 1 in the spleen). PET/CT exhibited a significantly higher sensitivity than SPECT/CT (100 % vs. 54 %, P < 0.001). TNR was significantly higher on PET/CT than on SPECT/CT (99.9 +/- 84.3 vs. 71.1 +/- 114.9, P < 0.001) in spite of a significant correlation (r = 0.692, P = 0.01). CONCLUSION: Ga-DOTATOC PET/CT has a higher diagnostic sensitivity than (111)In pentetreotide scans with SPECT/CT. The TNR on PET/CT is higher than that of SPECT/CT, which also suggests the higher sensitivity of PET/CT. (111)In pentetreotide SPECT/CT should be used carefully if it is used instead of (68)Ga DOTATOC PET/CT. PMID- 26550046 TI - Correlation of Consecutive Serum Thyroglobulin Levels During Hormone Withdrawal and Failure of Initial Radioiodine Ablation in Thyroid Cancer Patients. AB - OBJECTIVE: The aim of this study was to evaluate the value of thyroglobulin (Tg) kinetics during preparation of radioiodine ablation for prediction of initial radioiodine ablation failure in thyroid cancer patients. METHODS: Thyroid cancer patients after total thyroidectomy who underwent radioiodine ablation with 3-4 weeks of hormone withdrawal between May 2011 and January 2012 were included. Consecutive serum Tg levels 5-10 days before ablation (Tg1) and on the day of ablation (Tg2) were obtained. The difference between Tg1 and Tg2 (DeltaTg), daily change rate of Tg (DeltaTg/day) and Tg doubling time (Tg-DT) were calculated. Success of initial ablation was determined by the results of the follow-up ultrasonography, diagnostic radioiodine scan and stimulated Tg level after 6 to 20 months. RESULTS: A total of 143 patients were included. Failed ablation was reported in 52 patients. Tg2 higher than 5.6 ng/ml and Tg-DT shorter than 4.2 days were significantly related to a high risk of ablation failure. DeltaTg and DeltaTg/day did not show significant correlation with ablation failure. CONCLUSIONS: Thyroglobulin kinetics on consecutive blood sampling during hormone withdrawal may be helpful in predicting patients with higher risk of treatment failure of initial radioiodine ablation therapy in thyroid cancer patients. PMID- 26550048 TI - Prognostic Value of Metabolic Tumor Volume on (11)C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma. AB - PURPOSE: C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. METHODS: A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNRmax, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNRmax, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). RESULTS: Median PFS of all patients was 7.9 months (range 1.0-53.8 months). In univariate analysis, MTV (cutoff 35 cm(3)) was a significant prognostic factor for PFS (P = 0.01), whereas TNRmax (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). CONCLUSION: MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNRmax is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication. PMID- 26550049 TI - The Utility of Segmental Analysis in Cardiac I-123 MIBG SPECT in Parkinson's Disease. AB - PURPOSE: Cardiac images using I-123 metaiodobenzylguanidine (MIBG) are widely used to evaluate cardiac sympathetic denervation in Parkinson's disease (PD). The aim of this study was to evaluate the utility of segmental analysis on cardiac MIBG SPECT in PD patients. MATERIALS AND METHODS: In total, 36 patients with PD (n = 26) or essential tremor (ET, n = 10) who underwent MIBG cardiac SPECT were enrolled. The heart-to-mediastinum (H/M) ratios of MIBG uptake were acquired on planar images. For the segmental analysis of SPECT images, we evaluated the summed defect score (SDS) using a 17-segment model. The diagnostic abilities of H/M ratios and segmental parameters on MIBG SPECT were assessed by ROC curve analysis. RESULTS: The H/M ratios were significantly lower in PD than in ET patients (p < 0.05). On segmental analysis, SDS was significantly higher in PD patients than in the ET group (7.04 +/- 4.09 vs. 2.90 +/- 2.80; p = 0.006). The defect score of the anteroseptal region showed a significant difference between the groups (p = 0.002). The ROC analysis suggested only SDS (AUC = 0.785, p = 0.0003) and defect scores in the anteroseptal (AUC = 0.800, p < 0.0001) and inferior (AUC = 0.667, p = 0.013) regions showed significant diagnostic ability to differentiate PD from ET. CONCLUSIONS: Segmental parameters from cardiac MIBG SPECT images can provide additional information to differentiate PD from ET patients. Beyond H/M ratios from planar images, we recommend an MIBG SPECT study to evaluate sympathetic denervation in PD. PMID- 26550050 TI - Software-Based Hybrid Perfusion SPECT/CT Provides Diagnostic Accuracy When Other Pulmonary Embolism Imaging Is Indeterminate. AB - PURPOSE: To investigate the diagnostic performance of perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) in patients suspected to have pulmonary embolism (PE) but with indeterminate computed tomographic pulmonary angiography (CTPA) or planar ventilation/perfusion (V/Q) scans. METHODS: This retrospective study included two groups of patients. Group I consisted of 49 patients with nondiagnostic CTPA. These 49 patients underwent subsequent V/Q scans. Further Q-SPECTs were obtained in patients with indeterminate planar images and fused with existing CTPA. Group II consisted of 182 non-CTPA patients with indeterminate V/Q scans. These 182 patients underwent further Q-SPECT and separate noncontrast low-dose CT chest. Fusion Q-SPECT/CT scans were obtained through FDA-approved software and interpreted according to published criteria as positive, negative, or indeterminate for PE. Upon retrospective analyses, the final diagnosis was made using composite reference standards including all available clinical and imaging information for at least 6 month follow-up. RESULTS: In group I patients, 1 was positive, 24 were negative, and another 24 (49 %, 24/49) were indeterminate. In the subsequent 24 Q SPECT/CTPAs, 4 were positive, 19 were negative, and 1 was indeterminate (4.2 %, 1/24). In group II patients, 9 (4.9 %, 9/182) were indeterminate, 33 were positive, and 140 were negative. The combined nondiagnostic rate for Q-SPECT/CT was only 4.9 % (10/206). There was six false-negative and one false-positive Q SPECT/CT examinations. The sensitivity, specificity, and positive and negative predictive value of Q-SPECT/CT were 85.7 % (36/42), 99.4 % (153/154), 97.3 % (36/37) and 96.2 % (153/159), respectively. CONCLUSIONS: Q-SPECT/CT improves the diagnostic rate with promising accuracy in diagnosing PE that yields a satisfactory clinical verdict, especially when the CTPA and planar V/Q scan are indeterminate. PMID- 26550051 TI - The Alginate Layer for Improving Doxorubicin Release and Radiolabeling Stability of Chitosan Hydrogels. AB - PURPOSE: Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated. METHODS: Chitosan was chemically modified using a chelator for I 131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 degrees C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 degrees C for 12 days. RESULTS: Formatting the alginate crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 +/- 10 MUm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 +/- 0.8, 67.3 +/- 1.4, and 71.8 +/- 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the released Dox for 12 days was decreased to 47.6 +/- 1.4, 51.1 +/- 1.4, and 57.5 +/- 1.6 % for 0.25, 0.50, and 1.00 mg Dox used, respectively. The radiolabeling stability of DI-CSH in human serum was improved by alginate layer. CONCLUSIONS: The formation of alginate layer on the surface of the DI-CSH is useful for improving the drug release behavior and radiolabeling stability. PMID- 26550052 TI - The Utility of Intraoperative Handheld Gamma Camera for Detection of Sentinel Lymph Nodes in Melanoma. AB - Accurate identification of the sentinel lymph node (SLN) is an important prognostic factor for melanoma. In a minority of cases drainage to interval nodal basins, such as the epitrochlear region, are possible. Intraoperative handheld gamma cameras have been used to detect SLNs which are located in different anatomical localizations. In this case we report the utility of an intraoperative handheld gamma camera in the localization of epitrochlear drainage of distal upper extremity melanoma and its impact on surgical procedure. PMID- 26550053 TI - Multicentric Primary Angiosarcoma of Bone Mimicking Metastasis on (18)F-FDG PET/CT in a Patient with a History of Sigmoid Colon Cancer: a Case Report. AB - Primary angiosarcoma of the bone (PAB) is a rare and fatal high-grade malignant vascular bone tumor. We report a rare case of multicentric PAB mimicking bone metastasis in a 59-year-old female patient with a history of sigmoid colon cancer. This patient complained of lower back and pelvic pain and presented with multiple osteolytic bone lesions on plain radiography and pelvic computed tomography. First, bone metastasis of sigmoid colon cancer was suspected. However, on the (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) scan, the patient presented unusual multiple hypermetabolic osteolytic bone lesions involving contiguous bones of the lower half of the body. After bone biopsy, these lesions were confirmed to be multicentric PAB. To the best of our knowledge, this is the first case report of an (18)F-FDG PET/CT scan in a patient with multicentric primary bone angiosarcoma. PMID- 26550054 TI - Malignant Peritoneal Mesothelioma Masquerades as Peritoneal Metastasis on (18)F FDG PET/CT Scans; a Rare Diagnosis that Should Not Be Missed. AB - Malignant peritoneal mesothelioma (MPM) is a rare but fatal tumor. The clinical presentations and imaging findings are nonspecific and resemble various diseases, including peritoneal metastasis. Imaging findings of MPH on (18)F-(18)F fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) are diverse and not well described. We report the two cases of biopsy-proven MPH using (18)F-FDG PET/CT. In our cases, interesting disease patterns-including MPH arising from visceral peritoneal lining of kidney that suffer from polycystic disease and from the parietal peritoneum beneath the appendectomy scar-were presented. One case showed classical metastases localized within the abdominal cavity; while the other case exhibited the rare pattern of extensive multi-organ metastases. By knowing the possible variations and diagnostic pitfalls of (18)F-FDG PET/CT findings in MPM, more accurate interpretation of such mysterious cancer is attainable. PMID- 26550055 TI - Isolated Central Nervous System Relapse After 10 Years in a Case of Primary Testicular Lymphoma Detected on (18)F-FDG PET/CT. PMID- 26550056 TI - NaF18-PET/CT Imaging of Secondary Hyperparathyroidism. PMID- 26550057 TI - Tc-99m-HMPAO-Labeled Leukocyte SPECT/CT in Pediatrics: Detecting Candida albicans Tricuspid Endocarditis. PMID- 26550058 TI - Erratum to: Changes in Skeletal Tumor Activity on (18)F-choline PET/CT in Patients Receiving (223)Radium Radionuclide Therapy for Metastatic Prostate Cancer. AB - [This corrects the article DOI: 10.1007/s13139-014-0314-0.]. PMID- 26550061 TI - Hydrochemical Characterization of Groundwater Quality for Drinking and Agricultural Purposes: A Case Study in Rafsanjan Plain, Iran. AB - One of the important purposes of hydrology is to ensure water supply in accordance with the quality criteria for agricultural, industrial, and drinking water uses. The groundwater is the main source of water supply in arid and semi arid regions. This study was conducted to evaluate factors regulating groundwater quality in Rafsanjan plain. A total of 1040 groundwater samples randomly were collected from different areas of Rafsanjan. Then, each sample was analyzed for the major ions based on standard methods. The pH, SAR, EC, and TDS parameters and concentrations of Ca2+, Mg2+, and Na+ cations, and Cl-, [Formula: see text], [Formula: see text] and [Formula: see text] anions were measured. Also boron concentration in each sample was determined. Although, maximum and minimum values of EC and TDS linked to the Anar-Beyaz area and Eastern Urban, respectively, irrigation water EC condition, however, was critical in the study areas. The pH value in Western Urban was higher than the other areas, and its value for Anar Beyaz area was lower than the other areas, but pH value is at the optimal level in all the study areas. The results showed that hazard state with respect to Mg was critical except in Koshkoueiyeh and Anar-Beyaz areas, that these areas are marginal for irrigation use with little harm with reference to Mg. From the results, it was concluded that the status of boron concentration in study areas was critical. According to the hydrochemistry diagrams, the main groundwater type in different study areas was NaCl. Groundwater quality was not appropriate for drinking usage, and its status for agricultural practices was unsuitable in these areas. PMID- 26550059 TI - Role of gammadelta T Cells in Lung Inflammation. AB - The resident population of gammadelta T cells in the normal lung is small but during lung inflammation, gammadelta T cells can increase dramatically. Histological analysis reveals diverse interactions between gammadelta T cells and other pulmonary leukocytes. Studies in animal models show that gammadelta T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis. Lung inflammation threatens vital lung functions. Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of gammadelta T cells as well as interactions of these cells with other pulmonary leukocytes. PMID- 26550060 TI - A Systematic Review of Loneliness and Common Chronic Physical Conditions in Adults. AB - Loneliness is a prevalent and global problem for adult populations and has been linked to multiple chronic conditions in quantitative studies. This paper presents a systematic review of quantitative studies that examined the links between loneliness and common chronic conditions including: heart disease, hypertension, stroke, lung disease, and metabolic disorders. A comprehensive literature search process guided by the PRISMA statement led to the inclusion of 33 articles that measure loneliness in chronic illness populations. Loneliness is a significant biopsychosocial stressor that is prevalent in adults with heart disease, hypertension, stroke, and lung disease. The relationships among loneliness, obesity, and metabolic disorders are understudied but current research indicates that loneliness is associated with obesity and with psychological stress in obese persons. Limited interventions have demonstrated long-term effectiveness for reducing loneliness in adults with these same chronic conditions. Future longitudinal randomized trials that enhance knowledge of how diminishing loneliness can lead to improved health outcomes in persons with common chronic conditions would continue to build evidence to support the translation of findings to recommendations for clinical care. PMID- 26550062 TI - Proposal of ecographic classification for seroma after laparoscopic ventral hernia repair. AB - INTRODUCTION: Seroma is one of the most common complications after laparoscopic ventral hernia repair (LVHR), even if the incidence brought in literature is varying because definition and criterions of evaluation employed in the different studies are not always the same. This study proposes a classification for seroma after LVHR based on ultrasound findings, useful for an assessment of this complication. MATERIALS AND METHODS: On 93 patients submitted to LVHR an ultrasound of the abdominal wall after 3, 7, 15, 21 and 28 days and subsequently at a distance of 3 and 6 months was performed postoperatively. At each control site, sonomorphology characteristics and size of seroma (if present) were noted. RESULTS: At the end of the study using ultrasound findings obtained, a classification scheme for seroma articulated into three groups based on the parameters detected (site, sonomorphology character and volume) was developed, each of which is subdivided into five different classes to which a precise score is assigned. From the sum of the scores assigned, a value (between 3 and 15) that represents a prognostic index (PI) is obtained. A low PI is typical of small asymptomatic seroma that resolves spontaneously in a short time and without the need for invasive therapies; a high PI is typical of more or less symptomatic voluminous seroma that tends to persist for long periods and which often requires an interventional therapeutic approach. CONCLUSIONS: This proposed classification helps to perform a precise nosological assessment of seroma after LVHR, allowing the surgeon to predict the clinical and temporal evolution of this complication and to plan appropriate therapy from time to time. Furthermore this classification can represent a tool to assess the uniqueness of seroma formation in relation to surgical technique used, to the type of material employed and to the method of mesh fixing. PMID- 26550063 TI - Ultrasound in obstructive lung diseases: the effect of airway obstruction on diaphragm kinetics. A short pictorial essay. AB - The ultrasound study of the chest is showing a continuous development. This technique could be helpful in managing several chest diseases, but it is limited to the acoustic windows provided by intercostal spaces and by the inability to study healthy lung parenchyma and all intra-parenchymal diseases such as chronic obstructive lung disease (COPD), because the interaction between ventilated lung and ultrasound generates only artifacts. Currently, there are few applications of ultrasound that are useful in COPD, with recent studies providing some innovation potentially useful in clinical practice. The similarity of the trend between the time/volume curve of spirometry and the M-mode representation of diaphragm during forced breath allowed to identify the M-mode Index of Obstruction (MIO), an index obtained from the ratio between forced diaphragmatic excursion in the first second (FEDE1, cm) and the maximal expiratory diaphragmatic excursion (EDEMax, cm). MIO has shown a linear correlation with the ratio between forced expiratory volume in the first second (FEV1) and vital capacity (VC), used in spirometry to identify airways obstruction. The value of MIO seems to be lower in patients affected by airways obstruction as showed by a recent study. The technique is easy to learn and fast to perform and the analysis could be provided with any ultrasound machine equipped with M-mode. In conclusion, these findings, if confirmed by other studies, could suggest a new add-on screening tool for obstructive lung diseases, in particular COPD, that could be performed during a routine abdominal ultrasound exam. PMID- 26550064 TI - Ultrasound in newborns and children suffering from non-traumatic acute abdominal pain: imaging with clinical and surgical correlation. AB - The purpose of this article is to review ultrasonographic appearance of the most common causes of non-traumatic acute abdominal pain in pediatric patients and to understand the applications and limitations of this technique giving a practical approach showing different clinical cases. A pictorial review of cases was made presenting the most common causes of neonatal and pediatric non-traumatic acute abdominal pain; sonographic features are discussed. Ultrasound in conjunction with Color Doppler imaging is a valuable tool in the evaluation of neonatal and pediatric non-traumatic acute abdominal pain; causes of acute abdomen in children could vary depending on the ages of the children. PMID- 26550065 TI - Neck schwannoma diagnosed by core needle biopsy: a case report. AB - Here we present a case of a 58 year old man referred to our hospital to undergo neck and thyroid ultrasonography (US) following palpable neck mass. US revealed a solid hypoechoic nodule in right thyroid lobe, and a solid lesion on the right laterocervical neck region with ultrasound suspicious features of neoplastic lymph node. In order to achieve a diagnosis of the neck mass and to get a proper evaluation of the thyroid nodule, we decided to perform a fine-needle aspiration (FNA) of both lesions. At cytopathologic examination the thyroid nodule appeared as benign, while cytologic sampling of the neck lesion was inadequate for a proper evaluation. Thus, we performed core needle biopsy (CNB) of the neck lesion like recently proposed for thyroid lesions; also, to definitively exclude malignancy of thyroid nodule, this also underwent CNB. Histologic report of CNB confirmed benign thyroid nodule, while the neck lesion revealed a proliferation of neuronal type consistent with schwannoma. The patient has been addressed to clinical and ultrasonographic follow-up. CNB appears as a safe and minimally invasive approach to diagnose indeterminate neck masses and avoid unnecessary diagnostic surgery. PMID- 26550066 TI - A rare case of sigmoid colon obstruction in patient with ulcerative colitis: role of transabdominal ultrasound-guided biopsy. AB - INTRODUCTION: Endometriosis is a common chronic gynaecological disease affecting 10 % of women of reproductive age. Of these 5-12 % may present bowel endometriosis that may be asymptomatic or associated with aspecific symptoms even bowel obstruction. CASE PRESENTATION: The case of a 41-year-old woman with history of ulcerative colitis, previous diagnosis of ovarian endometriosis, recurrent abdominal pain not related to the menstrual cycle, with abdominal pain and obstinate constipation for 2 weeks was referred. The patient underwent colonoscopy, transabdominal ultrasound and ultrasound-guided fine-needle biopsy to have a diagnosis. DISCUSSION: Endometriosis should be considered in the differential diagnosis of every woman of childbearing age who presents with gastrointestinal or abdominal symptoms. As demonstrated in our case and by the burgeoning literature in this field, we believe that the role of transabdominal ultrasound should be reconsidered in the management of abdominal diseases because this examination associated with ultrasound-guided fine-needle biopsy allows, in expert hands, to obtain adequate histological samples avoiding patients to undergo more invasive tests to get a diagnosis. PMID- 26550067 TI - Accidental ultrasound finding of a big asymptomatic intestinal leiomyoma in an anticoagulated patient with macrohematuria. PMID- 26550068 TI - Ultrasound-guided percutaneous cholecystostomy in acute cholecystitis: case vignette and review of the technique. AB - Acute cholecystitis is a frequent condition. Although cholecystectomy is the indicated treatment of this entity, it cannot be performed in some high-risk surgery patients, such as critically ill or those with multiple comorbidities. In these non-uncommon scenarios, percutaneous cholecystostomy is the recommended alternative treatment, which allows immediate decompression and drainage of the acutely inflamed gallbladder and thus reducing the patient's symptoms and the systemic inflammatory response. Ultrasound is the imaging method of choice to guide the percutaneous cholecystostomy procedure due to its real-time guidance, lack of ionizing radiation and portability, avoiding the need to transfer unhealthy patients to the radiology department. We will review the ultrasound guided percutaneous cholecystostomy procedure, of special interest for radiologists, surgeons, and also intensive care and emergency physicians. PMID- 26550069 TI - Acute acalculous cholecystitis and cardiovascular disease: a land of confusion. AB - Acute acalculous cholecystitis (AAC) can be defined as acute inflammatory disease of the gallbladder without evidence of gallstones. The first case was reported in 1844 by Duncan et al.; however, some cases may have been missed previously in view of the complexity of the diagnosis. Several risk factors have been identified, and cardiovascular disease (CVD), in view of its multiple mechanisms of action, seems to play a key role. Atypical clinical onset, paucity of symptoms, overlap with comorbidities, and lack of robust, controlled trials result often in under or misdiagnosed cases. Moreover, laboratory results may be negative or not specific in the late stage of the disease, when a surgical treatment cannot be longer helpful if complications arise. A rapid diagnosis is therefore essential to achieve a prompt treatment and to avoid further clinical deterioration. In this short review, we would present the current evidence regarding epidemiology, pathophysiology, and clinical presentation of the complex relation between AAC and CVD. Then, we fully emphasize the role of ultrasound to achieve an early diagnosis and an appropriate treatment in suspected cases, reducing mortality and complications rates. PMID- 26550070 TI - Positive impact of elastography in breast cancer diagnosis: an institutional experience. AB - Elastography (ES) is a technique that, when associated with traditional B mode ultrasound (US), allows the degree of elasticity of tissue to be evaluated according to a color scale system. The aims of the study were to compare the diagnostic characteristics of two widely used techniques adopted in breast cancer screening; US and color Doppler (CD), with those of the same two techniques plus ES, and assessment of the same diagnostic characteristics when the three methods were applied to lesions < or >1 cm. Methods used included subjecting 212 women to investigations aimed at the early diagnosis of breast cancer outside the screening model, whereby 395 lesions were detected by US, ES, and CD, with a definitive diagnosis proved by histological exam. The diagnostic performance of US, ES, CD, and their combinations was calculated. The results showed that comparing the diagnostic characteristics of the three methods with reference to the definitive histological results for malignant breast lesions, the best diagnostic accuracy was obtained when US, ES, and CD were combined (0.837). For lesions <1 cm, diagnostic accuracy was 0.782, and for those >1 cm, it was 0.886. In the lesions <1 cm, which were more difficult to study, a positive ES score (>4) appeared to be sufficient to deepen the diagnosis, even though 35 % of the ES or US positive lesions were not malignant. By contrast, in lesions >1 cm, the probability of having a malignant lesion when all three tests were positive was very high (97 %). It was concluded that early diagnosis is a key factor in breast cancer, so an economically sustainable, non-invasive pathway is the target of diagnostic breast imaging. PMID- 26550071 TI - Role of US in evaluating breast implant integrity. AB - PURPOSE: To assess the diagnostic accuracy and inter-observer variability of ultrasound (US) in recognizing signs of intra or extra-capsular rupture of silicone breast implants by using the magnetic resonance imaging (MRI) findings as the reference standard. METHODS: 150 patients for a total of 300 implants underwent breast US and subsequently MR examination searching for signs of intra or extra-capsular rupture. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for breast US having MRI findings as the reference standard. Cohen's kappa statistics was used in order to assess inter-observer agreement for US. RESULTS: 170/300 (57 %) implant ruptures were detected at US (intra-capsular n = 110, extra-capsular n = 60). By comparing US findings with MR results, overall sensitivity, specificity, accuracy, PPV, and NPV of 79, 63, 70, 65, and 77 %, respectively, were found for breast US. In case of intra-capsular rupture, sensitivity, specificity, accuracy, PPV, and NPV of 63, 63, 63, 45, and 77 %, respectively, were obtained; 100 % values were found for extra-capsular rupture US diagnosis. CONCLUSION: US can be used as the first examination in patients with breast implants. US intra-capsular rupture detection requires further evaluation by MRI; in case of extra-capsular rupture US diagnosis, surgical implant removal could be proposed without further investigations. PMID- 26550072 TI - Core needle biopsy of soft tissue tumors, CEUS vs US guided: a pilot study. AB - PURPOSE: The purpose of this study was to evaluate the usefulness of contrast enhanced ultrasonography (CEUS) in the bioptic sampling of soft tissue tumors (STT) compared with unenhanced ultrasonography alone. METHODS: This is a prospective longitudinal study of 40 patients subjected to ultrasonography (US) guided core needle biopsy (CNB) to characterize a suspected STT. Three series of bioptic samplings were carried out on each patient, respectively using unenhanced US alone and CEUS in both the areas of the tumor enhanced or not by the contrast medium. All bioptic samples underwent a histological evaluation and the results were analyzed by comparing the histology of the biopsy with the definitive diagnosis in 15 surgically excised samples. RESULTS: 27 (67.5 %) of the 40 patients completed the entire study procedure; in 19 cases (70.3 %) the three bioptic samplings gave unanimous results, also when compared to the surgical specimen; in seven cases (25.9 %) use of CEUS allowed to obtain additional or more accurate information about the mass in question, compared to simple US guidance without contrast; in one patient (3.7 %) sampling obtained using unenhanced ultrasonography guidance and in the areas enhanced by the contrast agent had precisely the same results of the surgical specimen. CONCLUSIONS: CEUS, due to its ability to evaluate microvascular areas, has proven to be a promising method in guiding bioptic sampling of soft tissue tumor, directing the needle to the most significant areas of the tumor. Given the small number of patients evaluated in our study, to achieve statistically significant results, it would be appropriate to obtain a larger sample size, since the very first results seem to be encouraging and to justify the increase of the population. PMID- 26550074 TI - Joint effusion of the knee: potentialities and limitations of ultrasonography. AB - PURPOSE: This study aimed at comparing the diagnostic accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) for the detection of joint effusion of the knee. METHODS: For this retrospective study, approbation by the institutional review board was not required, and written informed consent from the patients was waived. One hundred and fifty-eight patients (83 men and 75 women; median age 41.2 years; age range 13-81 years) who underwent US and MRI of the knee were included in the study. The sensitivity and specificity of US with respect to MRI in the evaluation of the effusion of the knee and in each recess were compared. RESULTS: In evaluating joint effusion of the knee, compared with MRI, US correctly identified 78 of 96 patients with joint effusion, showing a sensitivity of 81.3 % and a specificity of 100 %, with a positive predictive value (PPV) of 100 % and a negative predictive value (NPV) of 77.5 % (p value = 0.001). Various results were obtained comparing ultrasound with MRI, regarding the various recesses. CONCLUSION: US showed high specificity and sensitivity in diagnosing knee joint effusion and could be used in patients who cannot undergo MRI. PMID- 26550073 TI - Inferior vena cava collapsibility loses correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure. AB - PURPOSE: Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear. METHODS: Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra abdominal pressure (IAP) phase via laparoscopic insufflation to 15 mmHg. IVC measurements were done at 1-2 cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter - min diameter)/max diameter * 100 %. Chi square, t test, correlation procedure (CORR) and Fisher's exact analyses were completed. RESULTS: A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46 +/- 15 years, with 75 % female and 69 % African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r (2) = 0.86, p < 0.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r (2) = 0.21, p = 0.52) or IAP (r (2) = 0.26, p = 0.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5 mm +/- 4.9) compared to spontaneous breathing (20.6 mm +/- 4.8, p = 0.04) and PPV (21.8 mm +/- 5.6, p = 0.01). CONCLUSION: IJV and IVC collapsibility correlated during spontaneous breathing but there was no statistically significant correlation during increased thoracic or intra-abdominal pressure. Increased intra-abdominal pressure was associated with a significant smaller maximal IVC diameter and cautions the reliability of IVC diameter in clinical settings that are associated with intra abdominal hypertension or abdominal compartment syndrome. PMID- 26550075 TI - Breast hamartoma: ultrasound, elastosonographic, and mammographic features. Mini pictorial essay. AB - Hamartomas, also known as fibroadenolipomas, are rare, benign formations that can develop in various organs, including the breast. They present clinically as a soft, mobile nodular lesions and are generally asymptomatic. They may be discovered incidentally during imaging studies performed for other reasons. Owing to the increasingly widespread use of mammographic screening, the diagnosis of breast hamartomas is on the rise. The masses are associated with specific mammographic and sonographic features that reflect their diverse tissue components. They also appear to present reproducible features on elastography. This article reviews the typical features of breast hamartomas seen on these three imaging modalities. PMID- 26550076 TI - Fracture of the sesamoid bones of the thumb associated with volar plate injury: ultrasound diagnosis. AB - The fractures of sesamoid bones of the hand are rare, sometimes the diagnosis is missed. We report a case of fracture of both the ulnar and radial sesamoids of the metacarpophalangeal (MCP) joint of the thumb. The trauma (hyperextension of the thumb during a soccer match) also caused a lesion of the volar plate. The diagnosis was made by ultrasound (US) and confirmed by CT scan. PMID- 26550077 TI - Muscle and fat mapping of the trunk: a case study. AB - The following case study examines the muscle and fat thickness of the trunk in a 25-year-old, former collegiate gymnast. Previous studies have quantified total and regional skeletal muscle mass using magnetic resonance imaging and muscle volume and distribution using ultrasound. However, to the best of our knowledge, the distribution and symmetry of skeletal muscle and subcutaneous adipose tissue (AT) of the anterior and posterior trunk have never been investigated. Ultrasound was used to identify skeletal muscle and AT thickness of 143 data points on the anterior portion of the trunk and 140 data points on the posterior portion of the trunk. Muscle thickness values in the anterior trunk ranged from 0.5 to 5.6 cm, and muscle thickness of the posterior trunk ranged from 0.6 to 6.6 cm. Total muscle volume of the trunk was 2935 and 4195 cm(3) for the anterior and posterior portions, respectively. The total predicted muscle mass in the anterior and posterior trunk was 7.4 kg. This case study begins to provide a picture of the distribution and symmetry of skeletal muscle and AT of the trunk. Future studies are necessary to confirm these findings and examine relationships among different populations. PMID- 26550078 TI - Diagnosis of abdominal mural aortic thrombus following discovery of common femoral artery and vein thrombosis by point-of-care ultrasound. AB - Acute limb ischemia (ALI) is a limb-threatening and life-threatening disease process. Mural aortic thrombosis (MAT) is a rare cause of ALI. While there is limited evidence on the use of bedside ultrasound for the detection of ALI or MAT, duplex ultrasound remains the standard in the diagnosis and ultimate medical decision-making in patients with acute and chronic limb ischemia. Point-of-care ultrasound may be used in the evaluation of patients with signs and symptoms of this disease entity. This is a case of a 79-year-old female with a complicated medical history, who presented with a pulseless right leg and abdominal tenderness. The patient quickly decompensated requiring intubation for airway protection. A post-intubation arterial blood gas (ABG) was unsuccessfully attempted in the right femoral artery, prompting an ultrasound-guided ABG. On B mode ultrasound evaluation, echogenic material was visualized in the right common femoral artery without evidence of Doppler flow signal. Additionally, a partially obstructing echogenic material was also noted at the femoro-saphenous vein junction with only partial compressibility by compression sonography. A computed tomography angiography of the aorta was performed indicating extensive infrarenal aortic thrombosis. The patient expired despite the relatively prompt diagnosis, highlighting the importance of early identification of acute arterial occlusion. PMID- 26550080 TI - Electrophysiological and anatomical background of the fusion configuration of diastolic and presystolic Purkinje potentials in patients with verapamil sensitive idiopathic left ventricular tachycardia. AB - BACKGROUND: It is unclear whether false tendons (FTs) are a substantial part of the reentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT). This study aimed to prove the association between FTs and the slow conduction zone by evaluating the electro-anatomical relationship between the so-called diastolic Purkinje (Pd) potentials and FTs using an electro anatomical mapping (EAM) system (CARTO). METHODS: The 1st protocol evaluated the spatial distribution of Pd and presystolic Purkinje (Pp) potentials in 6 IVLT patients using a conventional CARTO system. In the remaining 2 patients (2nd protocol), the electro-anatomical relationship between the Pd-Pp fusion potential and the septal connection of the FT was evaluated using an EAM system incorporating an intra-cardiac echo (CARTO-Sound). RESULTS: Pd potentials were observed in the posterior-posteroseptal region of the LV and had a slow conduction property, whereas Pp potentials were widely distributed in the interventricular (IV) septum. At the intersection of the 2 regions, which was located in the mid-posteroseptal area, both Pd and Pp potentials were closely spaced and often had a fused configuration. In the latter 2 patients (2nd protocol), it was confirmed that the intra-cardiac points at which the Pd-Pp fusion potential was recorded were located in the vicinity of the attachment site of the FT to the IV septum. In all patients, ILVTs were successfully eliminated by the application of radiofrequency at those points. CONCLUSION: FTs may at least partly contribute to the formation of the Pd potential, and thus form a critical part of the reentry circuit of ILVT. PMID- 26550079 TI - Radiofrequency ablation for thyroid nodules: which indications? The first Italian opinion statement. PMID- 26550082 TI - Pace mapping in the atrium using bipolar electrograms from widely spaced electrodes. AB - BACKGROUND: Pace mapping is a useful tool but is of limited utility for the atrium because of poor spatial resolution. We investigated the use of bipolar electrograms recorded from widely spaced electrodes in order to improve the resolution of pace mapping. METHODS: This prospective study included patients undergoing a clinical electrophysiology study. Unipolar pacing from either the superior or inferior lateral right atrium was performed to simulate atrial tachycardia. Twelve-lead electrocardiograms were recorded during pacing as a template. In addition, three intracardiac bipolar electrograms from a set of widely spaced electrodes were also recorded. Subsequently, unipolar pacing was performed from electrodes at known distances from the initial pacing site, and the morphology of P waves in the electrocardiogram and bipolar electrograms were compared with that of the template. Morphological comparison was performed by a cardiologist and by automated computerized matching. Spatial resolution was calculated as the minimum distance at which there was no match. RESULTS: Fifteen patients participated in the study. Distance at which differences in morphology were noted was smaller in the bipolar electrograms compared to that indicated by P waves in the electrocardiogram, when matched by the cardiologist (6.1+/-3.8 mm vs. 9.9+/-5.2 mm, p=0.012) or by automated analysis (4+/-0 mm vs. 9.9+/-4 mm, p<0.001). CONCLUSIONS: Use of three bipolar electrograms recorded from a set of widely spaced electrodes in the right atrium improves the resolution of pace mapping compared to that using P waves from surface electrocardiograms alone. PMID- 26550081 TI - Seasonal, weekly, and circadian distribution of ventricular fibrillation in patients with J-wave syndrome from the J-PREVENT registry. AB - BACKGROUND: Ventricular fibrillation (VF) in Brugada syndrome (BrS) is known to occur more frequently during nighttime and from spring to early summer. In this study, we investigated whether early repolarization syndrome (ERS) has the same seasonal, weekly, and circadian distribution of VF events as BrS using data from the "J-wave associated with prior cardiac event" (J-PREVENT) registry. METHODS: The study included 90 consecutive patients with BrS and 31 patients with ERS during a mean follow-up of 49+/-37 months. Follow-up data from implantable cardioverter-defibrillators were evaluated in all cases. RESULTS: In patients with ERS, the circadian distribution of VF episodes differed among the four 6-h periods, with a significant peak from midnight to 6:00 am (p<0.01) similar to that observed in BrS patients. However, VF occurred more frequently on weekends in patients with ERS, whereas on weekdays in patients with BrS (p<0.01). The months of peak VF occurrence also differed between the groups, with the frequency of VF episodes at peak between December and March in ERS patients and between March and June in BrS patients. In ERS patients, VF events had an inverse correlation with air temperature (r=-0.726, p<0.01). CONCLUSIONS: ERS and BrS patients show similar nighttime increases in the occurrence of VF, but different seasonal and weekly distributions, suggesting a pathophysiological difference between the two syndromes. PMID- 26550083 TI - Prevention of immediate recurrence of atrial fibrillation with low-dose landiolol after radiofrequency catheter ablation. AB - BACKGROUND: Immediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter ablation is commonly observed within 3 d after the procedure. The mechanism and pharmacological management of immediate AF recurrence remain unclear. METHODS: A total of 50 consecutive patients with paroxysmal AF were randomized to receive either low-dose landiolol (landiolol group) or a placebo (placebo group). In the landiolol group, intravenous landiolol (0.5 MUg kg(-1) min(-1)) was administered for 3 d after AF ablation. RESULTS: No serious adverse event associated with RF catheter ablation or landiolol administration was observed. The prevalence of immediate AF recurrence (<=3 d after RF catheter ablation) was significantly lower in the landiolol group than in the placebo group (16% vs. 48%, p=0.015). Although the postprocedural change in heart rate was significantly lower in the landiolol group compared to that in the placebo group, the changes in blood pressure and body temperature were not different between the two groups. Multiple logistic regression analysis revealed that landiolol treatment was the only independent predictor of immediate AF recurrence after ablation (odds ratio: 0.180; 95% confidence interval: 0.044-0.729; p=0.016). CONCLUSIONS: Prophylactic administration of low-dose landiolol after AF ablation may be effective and safe for preventing immediate AF recurrence within 3 d after AF ablation. PMID- 26550085 TI - Usefulness of the wearable cardioverter defibrillator in patients in the early post-myocardial infarction phase with high risk of sudden cardiac death: A single center European experience. AB - BACKGROUND: The effectiveness of the wearable cardioverter defibrillator (WCD) therapy in early post-myocardial infarction (MI) patients remains uncertain. METHODS: We analyzed the characteristics and outcomes of patients who received a WCD in the early post-MI phase. RESULTS: Twenty-four patients were followed-up for 8 months (range, 4-16 months). Two patients (8.3%) received appropriate shocks. Left ventricular ejection fraction improved after the WCD therapy (P<0.01). Fourteen patients (58%) received an implantable cardioverter defibrillator at the end of the follow-up period. CONCLUSION: Early post-MI patients at high risk of sudden cardiac death may benefit from WCD therapy. PMID- 26550084 TI - Topographic variability of the left atrium and pulmonary veins assessed by 3D-CT predicts the recurrence of atrial fibrillation after catheter ablation. AB - BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). However, the assessment of anatomical information and predictors of AF recurrence remain unclear. We investigated the relationship between anatomical information on the left atrium (LA) and pulmonary veins (PVs) from three-dimensional computed tomography images and the recurrence of AF after CA. METHODS: Sixty-seven consecutive AF patients (mean age: 62+/-10 years, median AF history: 42 (12; 60) months, mean LA size: 41+/-7 mm, paroxysmal: 56%) underwent CA and were followed for 19+/-10 months. The segmented surface areas (antral, posterior, septal, and lateral) and dimensions (between the anterior and posterior walls, the right inferior PV and mitral annulus [MA], the right superior PV and MA, the left superior PV and MA, and the mitral isthmus) of the LA were evaluated three dimensionally using the NavX system. The cross-sectional areas of the PVs were also evaluated. RESULTS: After the follow-up period, 49 patients (73%) remained free from AF. A multivariate analysis showed that the diameter of the mitral isthmus and cross-sectional area of the right upper PV were associated with AF recurrence (odds ratio: 1.070, CI: 1.02-1.12, p=0.001; odds ratio: 0.41, CI: 0.21-0.77, p=0.006). CONCLUSION: Enlargement of the mitral isthmus and a smaller right superior PV cross-sectional area were associated with AF recurrence. PMID- 26550086 TI - Clinical presentation and course of long QT syndrome in Thai children. AB - BACKGROUND: Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that can lead to lethal arrhythmia and sudden cardiac death in healthy young people. The clinical characteristics of LQTS are variable and depend on the subtype of long QT syndrome, which differ among populations. This single hospital-based case review study examined the clinical presentation of long QT syndrome and the outcomes of its treatment in 20 Thai children at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. METHODS: Inpatient and outpatient records of children (aged 0-14 years) diagnosed with long QT syndrome from January 1, 1998, to September 30, 2013, were retrospectively reviewed. Presentation at diagnosis, treatments, and clinical courses were collected and analyzed. In the 20 subjects, total Schwartz scores totaled 5.2+/-0.9 points, and mean age at diagnosis was 7.6+/-4.4 years (range, 1 day-13.8 years). The patients were assigned to one of 3 groups based on trigger events: 50% of patients had events at rest (sleep or at rest), 35% experienced adrenergic-mediated events (e.g., stress, exercise, startle), and 15% were asymptomatic. Excluding the 3 patients who died at first presentation, 100% of patients received a beta blocker, and 47.1% were treated with an automatic implantable cardioverter defibrillator (AICD). RESULTS: At follow-up (median=959 days; range, 1-4170 days), 4 patients (20%) were known to have died, 3 of whom died shortly after the diagnosis. Among patients who survived the initial event, 52.9% (9 of 17) experienced cardiac events (appropriate AICD shock, death, and/or syncope) during the follow-up period. The mean duration from diagnosis to cardiac event was 1420+/-759 days (range, 497-2499 days). CONCLUSIONS: All 20 patients with LQTS were mostly symptomatic at presentation. Owing to the geographical region and ethnicity of the Thai population, we conclude that the ratio of patients who develop cardiac symptoms at rest or during sleep might be higher than in other Asian countries. PMID- 26550087 TI - Comparison of the effects of bepridil and aprindine for the prevention of atrial fibrillation after cardiac and aortic surgery: A prospective randomized study. AB - BACKGROUND: Approximately one-third of the patients undergoing cardiovascular surgery reportedly experience paroxysmal atrial fibrillation (AF) during the postoperative period. However, the usefulness of antiarrhythmic drugs for preventing postoperative AF recurrence in the Japanese population has not been extensively studied. METHODS: From a total of 118 patients who developed postoperative paroxysmal AF between April 2009 and March 2011, 72 patients (45 men, mean age 68+/-8 years) requiring treatment for postoperative AF due to symptoms lasting >=30 min were enrolled to prospectively investigate the efficacy of oral bepridil (100 mg/day, n=37) or aprindine (40 mg/day, n=35). RESULT: The AF recurrence-free survival rates at 1, 3, 7, and 14 days were 100%, 94%, 57%, and 49%, respectively, in the aprindine group, and 100%, 97%, 86%, and 76%, respectively, in the bepridil group (P=0.028, aprindine vs. bepridil). CONCLUSION: Bepridil, at a fixed dose of 100 mg/day, was considered to be more effective than a routine dose of aprindine for the prevention of postoperative AF recurrence. PMID- 26550088 TI - Usefulness of brain natriuretic peptide for predicting left atrial appendage thrombus in patients with unanticoagulated nonvalvular persistent atrial fibrillation. AB - BACKGROUND: The CHADS2 scoring system is simple and widely accepted for predicting thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Although congestive heart failure (CHF) is a component of the CHADS2 score, the definition of CHF remains unclear. We previously reported that the presence of CHF was a strong predictor of left atrial appendage (LAA) thrombus. Therefore, the present study aimed to elucidate the relationship between LAA thrombus and the brain natriuretic peptide (BNP) level in patients with unanticoagulated NVAF. METHODS: The study included 524 consecutive patients with NVAF who had undergone transesophageal echocardiography to detect intracardiac thrombus before cardioversion between January 2006 and December 2008, at Hiroshima City Asa Hospital. The exclusion criteria were as follows: paroxysmal atrial fibrillation, unknown BNP levels, prothrombin time international normalized ratio >=2.0, and hospitalization for systemic thromboembolism. RESULTS: Receiver operating characteristic analysis yielded optimal plasma BNP cut-off levels of 157.1 pg/mL (area under the curve, 0.91; p<0.01) and 251.2 pg/mL (area under the curve, 0.70; p<0.01) for identifying CHF and detecting LAA thrombus, respectively. Multivariate analyses demonstrated that a BNP level >251.2 pg/mL was an independent predictor of LAA thrombus (odds ratio, 3.51; 95% confidence interval, 1.08-10.7; p=0.046). CONCLUSIONS: In patients with unanticoagulated NVAF, a BNP level >251.2 pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF. PMID- 26550090 TI - Coved-type ST-elevation during ablation of ischemic ventricular tachycardia. AB - A coved-type electrocardiogram (ECG) change in Brugada syndrome is suggested to be the result of abnormally delayed depolarization over the right ventricular outflow tract; however, ischemia of the conus branch of the right coronary artery presents the same ECG change. A 63-year-old man with a history of myocardial infarction demonstrated a transient coved-type ECG change during catheter ablation of ventricular tachycardia. The ECG change appeared during left ventricular mapping without any chest symptoms, and recovered spontaneously. A pilsicainide test was negative and a coved-type ECG did not appear during the perioperative or follow-up period. PMID- 26550089 TI - Right coronary artery perforation by an active-fixation atrial pacing lead resulting in life-threatening tamponade. AB - Cardiac tamponade resulting from perforation of a cardiac chamber is a relatively rare complication of pacemaker implantation. We report the first case of perforation of the right coronary artery related to the implantation of a screw in atrial pacing lead, presenting as life-threatening cardiac tamponade. We report the case of a 72-year-old woman with complete atrioventricular block and dyspnea on exertion. A permanent pacemaker was implanted with bipolar Medtronic active-fixation leads positioned in the right atrial appendage and at the right ventricular basal septum without any difficulty. Approximately 3.5 h after the procedure, the patient complained of nausea, and the systolic blood pressure decreased to less than 60 mmHg. Echocardiography revealed a large pericardial effusion. Because the effects of pericardiocentesis lasted for less than an hour, the patient underwent a thoracotomy. After evacuation of a massive hemopericardium, bright red blood was seen gushing out from the right coronary artery, which was located on the opposite site of the right atrial appendage where a small portion of the screw tip was observed to be penetrating the atrial wall. The right coronary artery perforation was repaired using autologous pericardium-reinforced 7-0 prolene mattress sutures. Perforation of the right coronary artery is a potential complication and should be part of the differential diagnosis of cardiac tamponade after pacemaker implantation. PMID- 26550091 TI - A case of paroxysmal atrial fibrillation with a non-pulmonary vein trigger identified by intravenous adenosine triphosphate infusion. AB - A 54-year-old woman was referred to our institution with frequent chest discomfort and was diagnosed with drug-refractory paroxysmal atrial fibrillation. Radiofrequency catheter ablation (RFCA) was performed using a three-dimensional electroanatomic mapping system. After completion of left and right circumferential pulmonary vein isolation (CPVI), an intravenous bolus of adenosine triphosphate (ATP, 20 mg) was administered to evaluate the electric reconduction between the pulmonary vein (PV) and left atrium (LA). Although no PV LA reconduction was observed, atrial fibrillation (AF) was reproducibly induced. As the duration of AF was very short (<20 s), no further RFCA to the LA was performed. One month later, the patient presented with frequent atrial tachyarrhythmias (ATs), and RFCA was repeated. Although no electric reconduction was observed in the left- or right-sided PVs, incessant ATs and AF were induced after an intravenous bolus administration of ATP. The earliest atrial activation site initiating ATs was consistently identified from electrodes positioned in the superior vena cava (SVC), and both ATs and AF were no longer inducible after electric isolation of the SVC. ATP-induced PV/non-PV ectopy may be a marker of increased susceptibility to autonomic triggers of AF and could potentially predict recurrent AF after CPVI. PMID- 26550092 TI - Ablation of an atriofascicular accessory pathway with a zero-fluoroscopy procedure. AB - A 16-year-old patient with recurrent palpitations and documented left bundle branch block superior axis wide complex tachycardia underwent an electrophysiological study and ablation with a zero-fluoroscopy procedure. The electrophysiological study showed a decremental antegrade conducting atriofascicular pathway. Three-dimensional CARTO-guided mapping of the tricuspid annulus in sinus rhythm was performed, and a distinct signal corresponding to the accessory pathway potential of the atriofascicular pathway was found in the posterolateral region. By using an SR0 sheath and a 4-mm-tip catheter, radiofrequency application was delivered at this point on the annulus and successfully eliminated conduction through the accessory pathway. PMID- 26550093 TI - Permanent cardiac pacing in a patient with persistent left superior vena cava and concomitant agenesis of the right-sided superior vena cava. AB - Persistent left superior vena cava (PLSVC) can be incidentally detected during pacemaker implantation from the left pectoral side. Optimal site pacing is technically difficult, and lead stability of the right ventricle (RV) can lead to such a situation. We describe a case of successful single-chamber pacemaker implantation in a 76-year-old woman with a PLSVC and concomitant agenesis of the right-sided superior vena cava, after failed attempts with the conventional procedure. The pacemaker had been working well after 12 months of follow-up. PMID- 26550094 TI - A case of dual atrioventricular nodal nonreentrant tachycardia: An unusual cause of tachycardia-induced cardiomyopathy. AB - We report on a 45-year-old female who developed cardiomyopathy due to incessant dual atrioventricular nodal nonreentrant tachycardia. Her condition was completely resolved by performing radiofrequency ablation of the slow pathway. PMID- 26550095 TI - Successful implantable cardioverter-defibrillator implantation through a communicating branch of the persistent left superior vena cava. AB - A left pectoral dual chamber implantable cardioverter-defibrillator (ICD) was successfully implanted through a small branch communicating between a persistent left superior vena cava (PLSVC) and right-sided venous drainage with long sheaths. Postprocedural computed tomography identified the communicating branch. ICD lead implantation through a PLSVC is challenging and sometimes unsuccessful. This case illustrates an alternative approach for ICD lead implantation in patients with a PLSVC. A PLSVC system should be carefully inspected for any communicating branches that can be utilized for lead implantation in order to increase the chance of success and minimize the risk of complications. PMID- 26550096 TI - Q wave and ST segment elevation in inferior leads: What is the diagnosis? PMID- 26549982 TI - Measurements of the [Formula: see text][Formula: see text] production cross sections in the [Formula: see text] channel in proton-proton collisions at [Formula: see text] and [Formula: see text] and combined constraints on triple gauge couplings. AB - Measurements of the [Formula: see text][Formula: see text] production cross sections in proton-proton collisions at center-of-mass energies of 7 and 8[Formula: see text] are presented. Candidate events for the leptonic decay mode [Formula: see text], where [Formula: see text] denotes an electron or a muon, are reconstructed and selected from data corresponding to an integrated luminosity of 5.1 (19.6)[Formula: see text] at 7 (8)[Formula: see text] collected with the CMS experiment. The measured cross sections, [Formula: see text] at 7[Formula: see text], and [Formula: see text] at 8[Formula: see text], are in good agreement with the standard model predictions with next-to-leading-order accuracy. The selected data are analyzed to search for anomalous triple gauge couplings involving the [Formula: see text][Formula: see text] final state. In the absence of any deviation from the standard model predictions, limits are set on the relevant parameters. These limits are then combined with the previously published CMS results for [Formula: see text][Formula: see text] in 4[Formula: see text] final states, yielding the most stringent constraints on the anomalous couplings. PMID- 26550097 TI - Preventing Relapse Following Smoking Cessation. AB - Cigarette smoking is the leading cause of preventable deaths worldwide. Long-term smoking cessation can drastically reduce people's risk for developing smoking related disease. The research literature points to a need for clearer operationalization and differentiation between smoking cessation and relapse prevention interventions and outcomes. That said, extensive meta-analyses and research studies have indicated that there are various efficacious smoking interventions that can both support smoking cessation and relapse prevention efforts. Specifically, behavioral treatments, relapse prevention psychotherapy, pharmacologic interventions, motivational enhancement, smoking reduction to quit, brief advice, alternative intervention modes (telephone, Internet, computer), self-help, and tailored treatments can help prepare smokers for longer-term abstinence. Although these methods vary on reach, they are relatively efficacious, particularly in combined formats. PMID- 26550098 TI - Seasonal variation in the distribution of daily stepping in 11-13 year old school children. AB - PURPOSE: Seasonality studies in adolescent's physical activity (PA) tend to report total PA (e.g. steps/day) rather than more specific detail such as steps/hour. This study compared the detailed changes in PA between seasons. METHODS: Thirty three adolescents (baseline age 12.2 +/- 0.3y) wore the activPAL activity monitor for 8 days on two occasions. RESULTS: Steps/day were higher in summer (Mdn = 12,879) than winter (Mdn = 10,512), p<.001. Steps/hour were significantly higher in summer compared to winter between 17:00 and 21:00 (p<. 044). No steps/day differences were found between boys and girls at either time point (p>.05), however, boys had significantly higher step counts in summer between '13:00-14:00' (p=.023), '19:00-20:00' (p=.032) and '20:00-21:00' (p=.023). CONCLUSION: Total steps/day masked sex differences within specific hours of the day, particularly evening times. Detailed daily patterns of PA are required to fully understand differences between sexes and across seasons. PMID- 26550101 TI - Fusion of a supernumerary tooth to right mandibular second molar: a case report and literature review. AB - Gemination or fusion is a rare occurrence in the mandibular posterior teeth. The aim of this article is to describe the problems encountered and the strategy employed in treating such cases. A 34 years old patient came with the complaint of spontaneous and radiating pain in the right mandibular posterior region. The tooth in concern was an anomalous 'double' second mandibular molar diagnosed as having necrotic pulp with chronic apical abscess of endodontic origin. The present case emphasizes the importance of identifying anatomical anomalies during treatment of fused teeth with supernumerary tooth, and the need for the use of advanced imaging modalities like CBCT which is a critical aid in the diagnosis of such cases. Fused teeth can be managed quite efficiently by an overall combined treatment including both endodontic and periodontal therapy. PMID- 26550099 TI - Association between X-ray repair cross-complementing group 1 gene polymorphisms and glioma risk: a systematic review and meta-analysis based on 22 case-control studies. AB - OBJECTIVES: Glioma is the most common central nervous system tumor. This systematic review and meta-analysis is aimed to systematically assess the association of XRCC1 polymorphisms with the risk of glioma. METHODS: Such databases as EMbase, PubMed, The Cochrane Library, the China National Knowledge Infrastructure (CNKI) platforms, VIP and WanFang were searched up to April 2015 to collect case-control studies of association between XRCC1 polymorphisms and glioma. Data were extracted and meta-analysis was conducted by using Stata 12.0 softwares. RESULTS: A total of 22 studies were included in the meta-analysis, including 18503 glioma patients and 24367 controls. The overall data indicated that XRCC1 Arg194Trp (C>T) polymorphism significantly increased glioma risk (allele C versus T: OR=0.72, 95% CI=0.55-0.93, CC versus TT: OR=0.55, 95% CI=0.46 0.67; CC versus CT+TT: OR=0.64, 95% CI=0.45-0.91 and CC+CT vs. TT: OR=0.61, 95% CI=0.51-0.74), especially in Asia ethnicity. XRCC1 Arg280His (G>A) polymorphism has no association with glioma (allele G versus A: OR=1.01, 95% CI=0.83-1.22; GG versus AA: OR=1.07, 95% CI=0.66-1.75; GA versus AA: OR=1.01, 95% CI=0.77-1.32; GG versus GA+AA: OR=1.01, 95% CI=0.84-1.22 and GG+GT versus AA: OR=1.06, 95% CI=0.67 1.69). XRCC1 Arg399Gln (G>A) polymorphism will significantly increase glioma risk in Asian (allele G versus A: OR=0.78, 95% CI= 0.72-0.84; GG versus AA: OR=0.56, 95% CI=0.47-0.66; GA versus AA OR=0.71, 95% CI=0.59-0.84; GG versus GA+AA: OR=0.76, 95% CI=0.68-0.84 and GG+GA vs. AA: OR=0.62, 95% CI=0.53-0.73) but not Caucasian ethnicity. XRCC1 Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Ser593Arg (C>G) and Glu491Lys (G>A) polymorphisms increased glioma risk in different degrees. CONCLUSION: This meta-analysis suggested that XRCC1 Arg194Trp and XRCC1 Arg399Gln (G>A) polymorphisms led to susceptibility to glioma in Asian but not Caucasian population. XRCC1 Glu491Lys (G>A), Pro161Leu (C>T), Leu387Leu (G>A), Pro602Thr (C>A), Thr304Ala (A>G) and Ser593Arg (C>G) polymorphisms will increase glioma risk. However, XRCC1 Arg280His (G>A) is irrelevant to the increased or decreased glioma risk. PMID- 26550100 TI - Clinical efficacy of dexmedetomidine versus propofol in children undergoing magnetic resonance imaging: a meta-analysis. AB - Dexmedetomidine, as a sole or combinable sedative, has served in pediatric sedation undergoing MRI. However, clinical effects of dexmedetomidine are still controversial. This meta-analysis was to assess the effects between dexmedetomidine and propofol in children undergoing MRI, especially outcomes and adverse events of patients. Multiple Electronic Database searched including MEDLINE, Embase and the Cochrane library, and updated to April 2015. All statistical analysis utilized review manager to perform, the Cochrane collaboration's software preparation and maintenance of Cochrane systematic reviews. Five trials with a total of 337 patients were included. Compared with propofol group, dexmedetomidine significantly increased the recovery time (WMD: 10.70 min; 95% CI: 4.26-17.13; P = 0.001). The duration of sedation did not appear to decrease for the patients who received dexmedetomidine than for those who received propofol (WMD: 19.96 min; 95% CI: -4.12-44.04; P = 0.1). There were statistically significant increased in the pediatric anesthesia emergence Delirium scores of 5-min after awakening (WMD: 2.40; 95% CI: 1.00 to 3.81; P = 0.0008) and 10-min after awakening (WMD: 3.06; 95% CI: 1.81 to 4.31; P < 0.00001) in patients who were treated with dexmedetomidine than propofol. Improved the prognosis of patients, nonetheless, dexmedetomidine must have an indispensable role to undergoing pediatric MRI scanning. Compared with propofol, however, dexmedetomidine did not induce the duration of sedation and might lead to a longer recovery time. PMID- 26550102 TI - Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis. AB - BACKGROUND: Numerous studies have focused on the association between MMP-12-82A>G polymorphism and cancer risk, but produced inconsistent results. Therefore, we performed a meta-analysis of case-control study to evaluate the association of MMP-12-82A>G polymorphism and cancer risk. METHODS: A systematic literature search was conducted among PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI) and Wangfang databases updated on May 1st, 2015. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between this polymorphism and cancer risk. RESULTS: A total of seventeen case-control studies with 7,450 cases and 7,348 controls were identified and analyzed. Overall, there was no statistically significant association between MMP-12-82A>G polymorphism and increased risk of cancer under all genetic models. Subgroup analysis by ethnicity observed that there is no strong relationship between MMP-12-82A>G polymorphism and cancer risk among Asian and European populations. Furthermore, stratified analysis based on the source of control revealed no statistically significant association between MMP-12-82A>G polymorphism and cancer risk either in hospital-based or population-based studies. However, when we stratified analysis based on cancer type, significant association was found in ovarian cancer, but not in other types of cancer. CONCLUSION: This meta-analysis suggests that MMP-12-82A>G polymorphism is not significantly associated with overall cancer risk. However, MMP-12-82A>G polymorphism may increase the susceptibility to ovarian cancer. PMID- 26550103 TI - CYP1A1 MspI polymorphism and susceptibility to lung cancer in the Chinese population: an updated meta-analysis and review. AB - BACKGROUND: Although many epidemiologic studies have investigated the CYP1A1 MspI gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. OBJECTIVE: To clarify the effects of CYP1A1 MspI polymorphisms on the risk of LC, an update meta-analysis was performed in only Chinese population. METHODS: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. RESULTS: A total of 22 studies including 3016 LC cases and 3932 controls were involved in this meta-analysis. Overall, significant association was found between CYP1A1 MspI polymorphism and LC risk when all studies in the Chinese population pooled into this meta-analysis (CC vs. TT: OR = 1.42, 95% CI = 1.11-1.80; CT + CC vs. TT: OR = 1.26, 95% CI = 1.06-1.50; CC vs. CT + TT: OR = 1.30, 95% CI = 1.04-1.61; C vs. T: OR = 1.21, 95% CI = 1.07-1.37). In subgroup analyses stratified by ethnicity and source of controls, significantly increased risk was found in Chinese Han people and in population-based studies. CONCLUSIONS: This meta-analysis provides the evidence that CYP1A1 MspI polymorphism may contribute to the LC development in the Chinese population and studies with large sample size and wider spectrum of population are warranted to verify this finding. PMID- 26550104 TI - Sphingosylphosphorylcholine in cancer progress. AB - Sphingosylphosphorylcholine (SPC) is a naturally occurring bioactive sphingolipid in blood plasma, metabolizing from the hydrolysis of the membrane sphingolipid. It has been shown to exert multifunctional role in cell physiological regulation either as an intracellular second messenger or as an extracellular agent through G protein coupled receptors (GPCRs). Because of elevated levels of SPC in malicious ascites of patients with cancer, the role of SPC in tumor progression has prompted wide interest. The factor was reported to affect the proliferation and/or migration of many cancer cells, including pancreatic cancer cells, epithelial ovarian carcinoma cells, rat C6 glioma cells, neuroblastoma cells, melanoma cells, and human leukemia cells. This review covers current knowledge of the role of SPC in tumor. PMID- 26550105 TI - Roles of antibody against oxygenized low density lipoprotein in atherosclerosis: recent advances. AB - Atherosclerosis is a chronic immune inflammatory disease. Atherosclerosis and relevant disease are threatening human life and health. Oxygenized low density lipoprotein (oxLDL) is a molecular basis in the pathogenesis of atherosclerosis and able to induce inflammation, stimulate immune system and interfere with lipid metabolism in the occurrence and development of atherosclerosis. Antibody against oxLDL has been an important molecule in the immune related pathogenesis of atherosclerosis. In available studies on atherosclerosis, antibody against oxLDL has been a focus, but how oxLDL acts to affect the atherosclerosis and relevant diseases, whether oxLDL is protective or detrimental, and whether oxLDL acts in different ways at different stages of atherosclerosis are still unclear. This paper focuses on the role of antibody against oxLDL in the atherosclerosis and relevant diseases, and summarizes the advances in this field, aiming to provide new clue and new methods for the therapy of atherosclerosis. PMID- 26550106 TI - Sphingosine kinase 1/sphingosine 1-phosphate signalling pathway as a potential therapeutic target of pulmonary hypertension. AB - Pulmonary hypertension is characterized by extensive vascular remodelling, leading to increased pulmonary vascular resistance and eventual death due to right heart failure. The pathogenesis of pulmonary hypertension involves vascular endothelial dysfunction and disordered vascular smooth muscle cell (VSMC) proliferation and migration, but the exact processes remain unknown. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid involved in a wide spectrum of biological processes. S1P has been shown to regulate VSMC proliferation and migration and vascular tension via a family of five S1P G-protein-coupled receptors (S1P1-SIP5). S1P has been shown to have both a vasoconstrictive and vasodilating effect. The S1P receptors S1P1 and S1P3 promote, while S1P2 inhibits VSMC proliferation and migration in vitro in response to S1P. Moreover, it has been reported recently that sphingosine kinase 1 and S1P2 inhibitors might be useful therapeutic agents in the treatment of empirical pulmonary hypertension. The sphingosine kinase 1/S1P signalling pathways may play a role in the pathogenesis of pulmonary hypertension. Modulation of this pathway may offer novel therapeutic strategies. PMID- 26550107 TI - Effect of chewing gum on the postoperative recovery of gastrointestinal function. AB - Postoperative gastrointestinal dysfunction remains a source of morbidity and the major determinant of length of stay after abdominal operation. There are many different reasons for postoperative gastrointestinal dysfunction such as stress response, perioperative interventions, bowel manipulation and so on. The mechanism of enhanced recovery from postoperative gastrointestinal dysfunction with the help of chewing gum is believed to be the cephalic-vagal stimulation of digestion which increases the promotability of neural and humoral factors that act on different parts of the gastrointestinal tract. Recently, there were a series of randomized controlled trials to confirm the role of chewing gum in the recovery of gastrointestinal function. The results suggested that chewing gum enhanced early recovery of bowel function following abdominal surgery expect the gastrointestinal surgery. However, the effect of chewing gum in gastrointestinal surgery was controversial. PMID- 26550108 TI - Accidental infusion leakage at subgalea in infants: report of 6 cases. AB - Infiltration remains the commonest iatrogenic injury within infants care. We report a series of 6 infants affected by accidental infusion leakage occurring in subgalea. They were applied wet-hot compresses by sterile gauze, and topically administrated mucopolysaccharide polysulfate (MPS) cream following hot compress. There was no skin impairment in all cases. Early recognition and appropriate care for topical skin are essential to minimize the extent of accidental infusion leakage. PMID- 26550109 TI - Meta-analysis of magnetic resonance imaging for the differential diagnosis of spinal degeneration. AB - To systematically evaluate the clinical significance of magnetic resonance imaging for the identification and diagnosis of spinal degenerative changes. We searched Cochrane Library, PubMed, EMbase, CNKI, WanFang Data, Medalink, VIP and CBM databases for clinical studies on the significance of magnetic resonance imaging for the differential diagnosis of spinal degeneration; retrieval time was from database building to October 2014. Two reviewers independently screened the literature, extracted data and evaluated methodological quality according to the inclusion and exclusion criteria. Meta-DiSc 1.4 software was used for meta analysis. The study included six documents, 10 independent results and a total of 505 individuals. Meta-analysis showed that: In the present study, the efficacy of magnetic resonance imaging in the differential diagnosis of cervical and lumbar degeneration was firstly analyzed and discussed using the Meta-Disc 1.4 software. SPE: chi(2) = 77.59, P = 0.000, I(2) = 88.4%; SEN: chi(2) = 167.25, P = 0.000, I(2) = 94.6%; DOR: Cochran-Q = 71.64, P = 0.000. Meta-analysis of random effect model showed that: SEN merge = 0.849 [95% CI (0.816,0.878)], SPE merge = 0.745 [95% CI (0.695, 0.792)], + LR = 2.735 [95% CI (1.600, -4.676)], - LR = 0.245 [95% CI (0.122, -0.493)], DOR merge = 21.158 [95% CI (5.234, -85.529)], SROC AUC = 0.8698; the results had good stability. Then the efficacy of magnetic resonance imaging in the differential diagnosis of cervical degeneration was analyzed and the results showed that: SPE: chi(2) = 6.92, P = 0.075, I(2) = 56.6%; SEN: chi(2) = 81.73, P = 0.000, I(2) = 96.3%; DOR: Cochran-Q = 12.71, P = 0.005. Meta analysis of random effect model showed that: SEN merge = 0.799 [95% CI (0.741, 0.850)], SPE merge = 0.769 [95% CI (0.683, -0.840)], + LR = 2.506 [95% CI (1.399, -4.489)], - LR = 0.363 [95% CI (0.149, -0.882)], DOR merge = 11.949 [95% CI (2.195, -65.036)], SROC AUC = 0.8210. The stability was good. Finally, analysis of six independent studies on the efficacy of magnetic resonance imaging in the differential diagnosis of lumbar degeneration was performed: SPE: chi(2) = 70.13, P = 0.000, I(2) = 92.9%; SEN: chi(2) = 78.35, P = 0.000, I(2) = 93.6%; DOR: Cochran-Q = 58.04, P = 0.000. Meta-analysis of random effect model showed that: SEN merge = 0.732 [95% CI (0.667, -0.791)] SPE merge = 0.883 [95% CI (0.843, 0.916)], + LR = 3.072 [95% CI (1.330, -7.091)], - LR = 0.190 [95% CI (0.063, 0.572)], DOR merge = 30.252 [95% CI (3.060, -299.13)], SROC AUC = 0.8994. Sensitivity analysis was performed by excluding each study individually and the results showed no significant changes in SEN and SPE merge, indicating good stability of the meta-analysis. Existing studies confirm that MRI had good sensitivity and specificity for the differential diagnosis of cervical and lumbar degeneration; the positive ratio in cervical and lumbar degeneration group was 3 to 10 times of that in non-degeneration control group; the efficacy for differential diagnosis was good; combined with the good maneuverability in clinical diagnosis of spinal degeneration, it can be used as effective and feasible method for clinical differential diagnosis of spinal degenerative diseases. PMID- 26550110 TI - The role of gene variants of the inflammatory markers CRP and TNF-alpha in cardiovascular heart disease: systematic review and meta-analysis. AB - It is widely acknowledged that cardiovascular heart disease (CHD) has a genetic influence. Several studies have investigated the role of inflammatory markers like C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) in the causation of cardiovascular diseases. Although there have been several positive studies associating CRP and TNF-alpha genes with CHD, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue. The meta-analysis was conducted with 22 articles of genetic association studies of CRP (G1059C rs1800947, C1444T rs1130864, C717T rs2794521 and G3872A rs1205) and TNF-alpha (C857T rs1799724, C863A rs1800630 and T1031C rs1799964) genes. To analyze the association of these variants with CHD we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian population using the same four models. CRP and TNF-alpha gene polymorphisms showed a positive significant association with CHD. This study provides evidence that rs2794521 of the CRP gene and rs1799724, rs1800630 and rs1799964 of the TNF-alpha gene polymorphisms may be risk factors to manifest CHD. The analysis of rs1800947 and rs1205 of the CRP gene yielded a protective effect in the pathogenesis of this disease. Only the analysis of the rs1130864 polymorphism showed a lack of association with CHD. To have conclusive outcomes it is necessary to integrate more studies to confirm our findings. PMID- 26550111 TI - Anticoagulant therapies versus heparin for the prevention of hemodialysis catheter-related complications: systematic review and meta-analysis of prospective randomized controlled trials. AB - Locking of central venous catheters with heparin is an accepted practice to maintain catheter patency between dialysis sessions. However, this practice may cause other adverse reactions. Although many studies suggest benefits of other catheter lock solutions over heparin on these grounds, no consensus has been reached for clinical practice. A systematic review and meta-analysis was performed of randomized controlled trials (RCT) that compared antimicrobial containing or citrate-alone catheter lock solutions with heparin alone in patients undergoing hemodialysis with central venous catheters. Medline, Cochrane Central Register of Controlled Trials from EMBASE, and PubMed were searched for articles published through June 2014. The primary outcomes were catheter-related bacteremia (CRB) and catheter malfunction (CM). The secondary outcomes were bleeding, exit-site infection (ESI), clinical sepsis, and all-cause mortality. Seventeen RCTs met the inclusion criteria. The meta-analysis showed that antimicrobial-containing and citrate-alone lock solutions were superior to heparin for preventing CRB (both P < 0.01). Although antimicrobial-containing lock solutions significantly affected clinical sepsis (P < 0.01), they did not affect ESI, bleeding, or all-cause mortality. Incidence of CM episodes was lower in patients receiving antibiotics + heparin and gentamicin + citrate (both P < 0.05), while other antimicrobial-containing and citrate-alone lock solutions showed no difference. Only citrate-alone lock solutions significantly decreased bleeding and ESI episodes (both P < 0.05). Compared with heparin, antimicrobial containing lock solutions more effectively prevent CRB and clinical sepsis. Antibiotics + heparin and gentamicin + citrate solutions showing better prevention of CM. Citrate-alone lock solutions result in fewer CRB, bleeding and ESI episodes. PMID- 26550112 TI - Polymorphisms in the intercellular adhesion molecule 1 gene and cancer risk: a meta-analysis. AB - OBJECTIVES: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis. DESIGN AND METHODS: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate. RESULTS: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility. CONCLUSIONS: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians. PMID- 26550113 TI - IL-6/STAT3/SOCS3 signaling pathway playing a regulatory role in ulcerative colitis carcinogenesis. AB - OBJECTIVE: Large-scale clinical studies have shown that ulcerative colities were related with colorectal cancer. In this study, animal model was established by AOM/DSS method to explore the activation of IL-6-STAT3-SOCS3 signaling pathway and the expression of pathway-related proteins in ulcerative colitis carcinogenesis, in order to lay a foundation for exploring the regulation mechanism of IL-6/STAT3/SOCS3 signaling pathway in ulcerative colitis carcinogenesis. METHOD: AOM/DSS modeling method was used to establish animal models of ulcerative colitis carcinogenesis; colonic mucosa specimens were collected at different time points for pathological examination. Immunohistochemical method and western blot were used to detect the expression of IL6, STAT3 and SOCS3 protein in the control group, UC model + empty vector group and UC model + STAT3 knockout group. RESULTS: In UC model + empty vector group, IL6 and STAT3 expression was increased as lesion degree increased (P < 0.05). The expression of SOCS3 was weakened and the degree of activation decreased (P < 0.05). IL6 expression increased in UC model + STAT3 knockout group (P < 0.05) while the expression of SOCS3 decreased; compared with the UC model + empty vector group, there was a significant difference (P < 0.05). CONCLUSION: The expression and activation of IL6 and STAT3 expression were enhanced in ulcerative colitis carcinogenesis, and their expression increased with the lesion degree increased, reflecting the disease progression to a certain extent. The expression and activation of SOCS3 expression decreased. STAT3 had a certain effect on the expression of SOCS3, playing a certain regulatory role in ulcerative colitis carcinogenesis. PMID- 26550114 TI - Up-regulation of miR-506 inhibits cell growth and disrupt the cell cycle by targeting YAP in breast cancer cells. AB - MicroRNAs (miRNAs) are a small class of non-coding RNAs that are extensively deregulated in various cancers. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-506 in breast cancer and to validate whether miR-506 could regulate proliferation of breast cancer cells by targeting YAP (Yes associated protein) gene. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-506 in breast cancer and adjacent non-cancerous breast tissues. To characterize the miR 506 function, MTT assays, colony formation assays, cell migration assays, cell invasion assays and cell cycle assays were used. Finally, luciferase reporter assays were performed to validate the regulation of a putative target of miR-506, in corroboration with western blot assays. We found that expression of miR-506 was commonly down-regulated in breast cancer cells and breast cancer specimens when compared with that in non-malignant breast epithelial cells and adjacent normal tissues. Up-regulation of miR-506 inhibited cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-506 directly bound to the 3'-untranslated region (3'-UTR) of YAP. Western blot analysis verified that miR-506 regulated the expression of YAP at the protein levels. These findings suggest that miR-506 exerts as a tumor suppressor in breast cancer and up-regulation of miR-506 expression inhibits cellular growth, cell migration and invasion as well as disrupt the cell cycle by targeting YAP. Our study demonstrates that the miR 506/YAP axis may help us better understand the molecular mechanisms of breast cancer progression. PMID- 26550115 TI - Effects of interleukin 10 polymorphisms on the development of hepatitis B virus infection: a systemic review and meta-analysis. AB - Current opinion varies in the roles of the IL-10 polymorphisms in the process of hepatitis B virus (HBV) infection. We have performed a systemic review and up dated meta-analysis including 37 eligible case-control studies to summarize all the available data on the association between IL-10 polymorphisms and development of HBV infection. In the present study, we found that the IL-10-1082 G/A, -592 C/A polymorphisms were associated with a significantly decreased risk of chronic HBV infection (AA + GA vs. GG: P = 0.003, OR = 0.55, 95% CI = 0.37-0.82; AA vs. CA + CC: P = 0.03, OR = 0.83, 95% CI = 0.71-0.98). While the -819 C/T TT carriers were associated with a borderline significantly decreased risk of chronic HBV infection (TT vs. CT + CC: P = 0.05, OR = 0.82, 95% CI = 0.68-1.00). Significant result was observed in the association between IL-10-1082 G/A polymorphism and HBV clearance (AA vs. GG: P = 0.04, OR = 1.33, 95% CI = 1.01-1.75). In addition, significant association was found between the -1082 G/A, -819 C/T polymorphisms and an increased risk of progression of HBV infection from asymptomatic carrier to chronic hepatitis B (AA + GA vs. GG: P = 0.0003, OR = 2.13, 95% CI = 1.41 3.22; TT + CT vs. CC: P = 0.005, OR = 1.53, 95% CI = 1.13-2.07), whereas the -592 C/A polymorphism was associated with a significantly decreased risk of progression from asymptomatic carrier to hepatocellular carcinoma (AA vs. CC: P = 0.02, OR = 0.63, 95% CI = 0.43-0.92). Our meta-analysis suggested that the IL-10 polymorphisms might be associated with a decreased risk of chronic HBV infection, while the -1082 AA carriers might be more likely to clear HBV following acute infection. In addition, these three polymorphisms might cast in roles of the progression of HBV infection. PMID- 26550116 TI - Evaluation of activity of an estrogen-derivative as cardioprotector drug using an ischemia-reperfusion injury model. AB - Myocardial ischemia/reperfusion injury is a serious problem involved in cardiovascular diseases. There data which indicate that some steroids induce cardioprotective effects on myocardial ischemia-reperfusion injury; however their activity and the molecular mechanism involved on myocardial ischemia-reperfusion injury are very confusing. Therefore, in this study some estrogen derivatives (compound 3 to 7) were synthesized with the objective of evaluating its activity on myocardial ischemia/reperfusion injury using an isolated heart model. Additionally, molecular mechanism involved in the activity exerted by the compounds 3 to 7 on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in absence or presence of following compounds; prazosin, metoprolol, indomethacin and nifedipine. The results showed that 7 reduce infarct size compared with the estrone and other estrogen derivatives (compounds 3, 4, 5, and 6). Other results showed that 7 significantly increase the perfusion pressure and coronary resistance in isolated heart in comparison with estrone, 3, 4, 5, and 6. Finally, other data indicate that 7 increased the left ventricular pressure in a dose-dependent manner; however, this phenomenon was significantly inhibited by nifedipine. In conclusion, all these data suggest that 7 exert a cardioprotective effect through calcium channels activation and consequently induce changes in the left ventricular pressure levels. This phenomenon results in decrease of myocardial necrosis after ischemia and reperfusion. PMID- 26550117 TI - Prognostic value of melanoma cell adhesion molecule expression in cancers: a meta analysis. AB - Melanoma cell adhesion molecule (MACM) has been reported in many studies as a novel bio-marker for its prognosis value in cancers. But the prognosis significance of MACM expression in cancer remains inconclusive. Therefore, we conducted a system review and meta-analysis to assess its prognosis value in cancers. A systematic search through Pubmed, EMBASE and Cochran Library database was conducted. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the prognosis value of MACM expression. Eleven studies with 2657 cases were included after sorting out 462 articles for this meta-analysis. The results of the fixed-model depending on the heterogeneity in studies demonstrated that MACM expression was significantly associated with overall survival (OS) in cancer (HR=2.84, 95% CI: 1.10-7.31, P<0.00001). Furthermore, subgroup analysis indicated that high expressed MACM predicted a poor OS in both Asian (HR=2.52, 95% CI: 1.80-3.52, P<0.00001) and Caucasian (HR=2.40, 95% CI: 2.01-2.88, P<0.00001). In conclusion, high expression of MACM was significantly associated with a poor prognostic outcome in cancer. MACM can be regarded as a novel bio marker in different types of cancers and can be used to evaluate the prognosis of therapeutic effect during clinical practices. PMID- 26550118 TI - Busulfan plus fludarabine compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematologic neoplasms: a meta-analysis. AB - OBJECTIVES: The aim of the article is to critically appraise and synthesize available evidence regarding the efficacy and regimen-related toxicity (RRT) of Busulfan plus fludarabine (BuFlu) compared to busulfan plus cyclophosphamide (BuCy) as a conditioning regimen, prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic neoplasms. METHODS: A meta analysis was attempted on clinical controlled trials (CCTs), randomized or non randomized controlled trials (RCTs or non-RCTs), comparing BuCy with BuFlu. We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and event-free survival (EFS), acute graft-versus-host-disease (aGVHD). Chronic GVHD (extensive) and other toxicity were secondary endpoints. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta analysis. RESULTS: Nine clinical controlled trials were included, of which 4 tries were RCTs involving 584 patients and the other 5 were non-RCTs involving 571 patients. The cumulative incidences of OS, EFS, acute graft-versus-host disease (aGVHD) were not significantly different between the two regimens. The non-relapse mortality was higher in BuCy but non-significant increment (RR=1.48, 95% CI: [0.97-2.26]). Liver related toxicity was significantly higher with BuCy compared to BuFlu (RR=1.90, 95% CI: [1.00-3.61]). CONCLUSION: Liver related toxicity is significantly lesser with BuFlu, but BuFlu regimen has no significant benefits compared with BuCy in OS, EFS, aGVHD. For all this, the weight of evidence favors BuFlu over BuCy as a first choice-conditioning regimen for patients with hematologic neoplasms, especially for people who have poor liver function. PMID- 26550119 TI - Epithelial-mesenchymal transition and mesenchymal-epithelial transition response during differentiation of growth-plate chondrocytes in endochondral ossification. AB - For linear longitudinal bone elongation, the stem-like progenitor chondrocytes distributed in resting zone (RZ) of growth plate have a capacity to differentiate towards the spindle chondrocytes in proliferative zone (PZ), then towards the columnar and tightly adjacent chondrocytes in hypertrophic zone (HZ). We hypothesized this process of endochondral ossification with cells morphological change was occurred along with the inter-conversion between epithelial to mesenchymal cell types. Consistent with this hypothesis, our study demonstrated the chondrocytes highly expressed mesenchymal-like biomarkers and loss of epithelial surface markers in PZ, while converse in RZ and HZ of the growth plate in mice distal tibia in vivo. To further determine these process and correlation regulatory pathway, the 4-week old male and female mice were treated with estradiol cypionate or oxandrolone, then investigated the response of epithelial- and mesenchymal biomarkers, and demonstrated that estrogen blocked the EMT process from RZ to PZ while androgen promoted MET from PZ to HZ. Our observations supported the hypotheses that the growth plate firstly go through EMT from RZ to PZ, then MET process from PZ to HZ during the epiphyseal fusion. Our results could interpret the different roles of estrogen and androgen in growth plate cartilage when endochondral ossification. PMID- 26550120 TI - Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. AB - BACKGROUND/AIMS: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. METHODOLOGY: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). RESULTS: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). CONCLUSIONS: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID- 26550121 TI - Diagnostic performance of ADCs in different ROIs for breast lesions. AB - OBJECTIVE: The purpose of this study was to explore the diagnostic performance of apparent diffusion coefficient (ADC) values for breast lesions by different measuring methods and find out the optimum measuring method. METHODS: ADCW-mean and ADCW-min were obtained by whole-measurement method, while ADCmean and ADCmin were extracted by spot-measurement method. Four ADCs were analyzed by One-way ANOVA and Independent T-test. The diagnostic performances of these four ADCs were calculated by receiver operating characteristics (ROC) curves and the area under the curves (AUC) were compared through Z-test. RESULTS: For the whole-measurement method, there were significant differences between malignant and benign lesions (ADCW-mean=1.014+/-0.197 for malignant, ADCW-mean=1.650+/-0.348 for benign, F=37.511, P<0.001; ADCW-min=0.627+/-0.144 for malignant, ADCW-min=1.245+/-0.290 for benign, F=41.446, P<0.001), as well as the spot-measurement method (ADCmean=1.010+/-0.234 for malignant, ADCmean=1.648+/-0.392 for benign, F=34.580, P<0.001; ADCmin=0.817+/-0.203 for malignant, ADCmin=1.411+/-0.357 for benign, F=40.039, P<0.001). The optimal diagnostic threshold of ADCW-mean, ADCW-min, ADCmean, and ADCmin values were 1.223*10(-3) mm(2)/s, 0.897*10(-3) mm(2)/s, 1.315*10(-3) mm(2)/s, and 1.111*10(-3) mm(2)/s, respectively. ROC curves indicated that the AUC for ADCW-min (0.969) was statistically significant higher than the AUC for ADCW-mean (0.940; Z=2.473, p=0.013), ADCmean (0.919; Z=3.691, P=0.000), and ADCmin (0.928; Z=3.634, P=0.000). The AUC for ADCW-mean was also significantly higher than the AUC for ADCmean (Z=2.863, P=0.004). CONCLUSION: The results provided evidence that the most reliable and accurate value in demonstrating the limitation of diffusion may be ADCW-min, and it has the highest diagnostic value in distinguishing breast lesions from malignant to benign. PMID- 26550122 TI - Protective effect of neovibsanin B on spatial cognitive functions of rats with cerebrovascular hypoperfusion. AB - Neovibsanins are believed to be promising candidates for the development of novel therapeutic agents to treat neurological diseases like Alzheimer's disease. It has been shown that chronic cerebral hypoperfusion is linked to neurodegenerative disorders and their subsequent cognitive impairment. In the present study effect of neovibsanin B (NVB) on spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. The cerebrovascular hypoperfusion rat model was prepared by bilateral common carotid arteries occlusion (2VO). Morris water maze (MWM) test was employed to examine the effect of NVB on spatial cognitive function before and after 2VO intervention. The animals were divided into two groups; long-term memory (LTM) and short-term memory (STM) groups. Each of the groups was subdivided into 3 subgroups: control, untreated and NVB treated groups. After ten weeks of the surgery, all the subgroups were tested with MWM. The results of working memory test for both control and NVB treated groups revealed that escape latency time and total distance travelled were significantly lower compared to untreated group. Similarly, the maze test performance was observed to be significantly improved for control and NVB treated groups. Moreover, the probe memory test performance for control and NVB treated groups was markedly better than untreated group. Thus NVB has a significant effect on the spatial cognitive preservation in rats with chronic cerebral hypoperfusion. Thus NVB can be a promising agent for the spatial cognitive functions improvement. PMID- 26550124 TI - Comparison of clinical and radiological outcomes after automated open lumbar discectomy and conventional microdiscectomy: a prospective randomized trial. AB - OBJECTIVE: Microdiscectomy (MD) is the gold standard for surgical discectomy. As a minimally invasive discectomy, automated open lumbar discectomy (AOLD) is designed to preserve annular integrity and disc height as well as effectively remove herniated disc and degenerated disc material. However, there have been no prospective clinical studies comparing their effectiveness. The study was designed to compare clinical and radiological outcomes after AOLD with those of MD. METHODS: Seventy-eight patients were evaluated for unilateral leg pain with the presence of disc herniation on magnetic resonance imaging (MRI) scans at a single attributable level. Sixty-two patients were enrolled; 33 patients (53%) were randomly assigned to the AOLD group and the remaining 29 patients (47%) were assigned to the MD group. Follow-up assessment was performed for 19 of the AOLD patients and 17 of the MD patients. The average follow-up period was 20 months. Clinical and functional outcomes were assessed using VAS and ODI scores. Change of disc height (DH), instability, and disc degeneration were assessed from radiographs, while Modic change and reherniation were assessed using MRI scans. RESULTS: Postoperative VAS scores for leg pain and ODI scores for function were significantly improved in both groups. Postoperative VAS for back pain tended to decrease in the MD group but the decrease was statistically insignificant (P = 0.081). The postoperative VAS for back pain was significantly reduced in the AOLD group (P = 0.012). Patients from the MD group showed greater DH reduction than the AOLD group (P = 0.049). The MD group experienced greater disc degeneration and Modic change than the AOLD group. Follow-up MRI revealed 2 cases of reherniation in the AOLD group; 1 case was symptomatic, the other was asymptomatic. CONCLUSIONS: AOLD showed comparable clinical and radiological outcomes to conventional MD. AOLD preserves the central disc and removes only the loose degenerative disc fragments that are the main cause of reherniation by small annulotomy. Our results suggest that preservation of the central disc prevents loss of disc height and segmental instability, which is related to postdiscectomy back pain. PMID- 26550125 TI - CD14 gene-159C/T polymorphism and coronary artery disease: a meta-analysis involving 4467 subjects. AB - BACKGROUND: The cluster of differentiation antigen 14 (CD14) gene-159C/T polymorphism has been implied to be associated with coronary artery disease (CAD) susceptibility. However, the separate studies results are still conflicting between each other. OBJECTIVE AND METHODS: To investigate the relationship between CD14 gene-159C/T polymorphism and CAD, a meta-analysis including 4467 subjects from 7 individual studies was performed. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals. RESULTS: There was a significant association between CD14 gene -159C/T polymorphism and CAD in the whole population under allelic (OR: 1.280, 95% CI: 1.000-1.630, P=0.05), recessive (OR: 1.760, 95% CI: 1.120-2.750, P=0.01), homozygous (OR: 1.693, 95% CI: 1.008-2.843, P=0.046), and additive genetic models (OR: 1.278, 95% CI: 1.000-1.633, P=0.050). No significant association was found between them under dominant (OR: 0.580, 95% CI: 0.310 1.110, P=0.10) and heterozygous genetic models (OR: 1.334, 95% CI: 0.870-2.045, P=0.186). In the subgroup analysis, a significant association was detected in Chinese population (P<0.05), while there was no significant association in the Caucasian subgroup (P>0.05). CONCLUSIONS: CD14 gene -159C/T polymorphism was significantly associated with CAD susceptibility, particularly in the Chinese population. The person with T allele of CD14 gene -159C/T polymorphism might predispose to CAD. There was no distinct association between them in the Caucasian subgroup. PMID- 26550123 TI - Efficacy of dexmedetomidine on postoperative nausea and vomiting: a meta-analysis of randomized controlled trials. AB - PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently searched PubMed, Embase and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs). The meta-analysis was performed with Review Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) = 0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95% CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 ug/kg (RR = 0.46, 95% CI: 0.34 to 0.62) and 1.0 ug/kg (RR = 0.29, 95% CI: 0.12 to 0.75), respectively. The antiemetic effect can only be achieved intravenously, not epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that of widely used agents, such as propofol, midazolam etc., but better than opioid analgesics. Moreover, application of dexmedetomidine reduced intraoperative requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to 0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority to placebo, but not to all other anesthetic agents on PONV. And this efficacy may be related to a reduced consumption of intraoperative opioids. PMID- 26550126 TI - Screening feature genes of lung carcinoma with DNA microarray analysis. AB - Lung carcinoma is the most common and aggressive malignant tumor with poor clinical outcome. Identification of new marker of lung cancer is essential for the diagnosis and prognosis of the disease. To identify differentially expressed genes (DEGs) and find associated pathways that may function as targets of lung cancer. Gene expression profiling of GSE40791 were downloaded from GEO (Gene Expression Omnibus), including 100 normal specimens and 94 lung cancer samples. The DEGs were screened out by LIMMA package in R language. Besides, novel genes associated with lung cancer were identified by co-expression analysis. Then, GO enrichment and transcription binding site analysis were performed on these DEGs, and novel genes were predicted using DAVID. Finally, PPI network was constructed by String software in order to get the hub codes involved in cancer carcinoma. A total of 541 DEGs were filtered out between normal samples and patients with lung carcinoma, including 155 up-regulated genes and 386 down-regulated genes. Additionally, nine novel genes, CA4, CDC20, CHRDL1, DLGAP5, EMCN, GPM6A, NUSAP1, S1PR1 and TCF21, were figured out. The transcription biding site analysis showed that these genes were regulated by LHX3, HNF3B, CDP, HFH1, FOXO4, STAT, SOX5, MEF2, FOXO3 and SRY. Hub codes as BUB1B, MAD2L and TOP2A may play as target genes in lung carcinoma in the result of PPI network analysis. Newly predicted genes and hub codes can perform as target genes for diagnose and clinical therapy of lung cancer. PMID- 26550127 TI - Impacts of fluorescent superparamagnetic iron oxide (SPIO)-labeled materials on biological characteristics and osteogenesis of bone marrow mesenchymal stem cells (BMSCs). AB - The aim of this study was to investigate the impacts of fluorescent superparamagnetic iron oxide particles (Molday ION Rhodamine B, MIRB) on bioactivities and osteogenetic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). The Cell Counting Kit-8 (CCK-8) method was used to detect the proliferation of superparamagnetic iron oxide (SPIO)-labeled BMSCs and observed the distribution of MIRB in cells; real time -polymerase chain reaction (RT-PCR) method was used to analyze the expressions of such osteogenesis-related genes as bone sialoprotein, alkaline phosphatase (ALP), RUNX2, bonemorphogeneticprotein-2 (BMP-2), type 1 collagen (COL-1) and type 3 collagen (COL-3); ALP-Alizarin red staining and poly-biochemical analyzer were used to qualitatively and quantitatively analyze the osteogenetic metabolites. The labeled MIRB particles distributed in the cytoplasm of BMSCs, the diameter of larger particles could be up to several hundred nanometers, and concentrated around the nuclei, the particles far away from the nuclei were smaller, but the labeled-cells' skeletons and adherent morphology did not change significantly; under the concentration of 25 MUg Fe/mL of, MIRB did not affect cellular viabilities of BMSCs, but the gene expressions of bone sialoprotein, ALP, RUNX2 and BMP-2 were decreased, and the secretion amount of ALP and osteocalcin were also declined. MIRB would not affect the proliferation and cell structures of BMSCs, but the SPIO particles aggregated and formed larger granules around the nuclei, which might affect the osteogenesis of BMSCs. PMID- 26550129 TI - Accuracy and efficacy of osteotomy in total knee arthroplasty with patient specific navigational template. AB - This study develops and validates a novel patient-specific navigational template for total knee arthroplasty (TKA). A total of 70 patients who underwent TKA were randomized and divided into conventional method group and navigational template group. In the navigational template group, the patient-specific navigational templates were designed and used intraoperatively to assist 35 patients with knee arthroplasty. Information on operation time and blood loss was recorded. After surgery, the positions of the prosthesis were evaluated using CT scan and X-rays. Analysis showed significant differences in errors between the two techniques. In addition, mean operation time and mean blood loss were statistically and significantly lower in the navigational template group than in the conventional group. Overall, the navigational template method showed a high degree of accuracy and efficacy. PMID- 26550128 TI - Anti-tumor effect of RGD modified PTX loaded liposome on prostatic cancer. AB - In this study, we report an active targeting liposomal formulation directed by a novel peptide (RGD) that specifically binds to the integrins receptors overexpressed on prostatic cancer cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of RGD modified liposomes on PC-3 cells and DU145 cells. The uptake efficiency of RGD-LP was 5.2 times higher than that of LP on PC-3 cells. The uptake efficiency of RGD-LP was 3.2 times higher than that of LP on DU145 cells. The anti-proliferative activity of RGD-LP-PTX against PC-3 cells and DU145 cells were much stronger compared to that of LP-PTX and free PTX, respectively. The tumor spheroids experiment revealed that RGD-LP-PTX was more efficaciously internalized into tumor spheroids than LP in both PC-3 cells and DU145 cells. Compared to LP-PTX and free PTX, RGD LP-PTX showed the greatest tumor growth inhibitory effect in vivo. In brief, the RGD-LP may be an efficient targeting drug delivery system for prostatic cancer. PMID- 26550130 TI - Single-agent bortezomib or bortezomib-based regimens as consolidation therapy after autologous hematopoietic stem cell transplantation in multiple myeloma: a meta-analysis of randomized controlled trials. AB - The efficacy and safety of single-agent bortezomib or bortezomib-based regimens as consolidation therapy after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM) has been in question. To address the issue, we conducted a meta-analysis of two randomized double-blind placebo controlled studies involving a total of 691 patients. The primary outcomes of interest were progression-free survival (PFS) and response rate. Secondary outcomes included overall survival (OS) and adverse events. There was a marked benefit in 3-year PFS with bortezomib (Odds Ratio [OR] = 1.52, 95% confidence interval [CI] = 1.11 to 2.08), whereas there was no difference in 3-year overall survival (OS; OR = 0.91, 95% CI = 0.60 to 1.37). More bortezomib-treated paitents achieved at least a very good partial response (>= VGPR) (OR = 1.73, 95% CI = 1.19 to 2.51). The rate of complete response or near-complete response (CR/nCR) was significantly higher with bortezomib consolidation therapy (OR = 1.62, 95% CI = 1.18 to 2.22). For adverse events, more patients in the bortezomib consolidation therapy arm experienced peripheral neuropathy (OR = 4.03, 95% CI = 2.72 to 5.96). Significant differences were also seen with those experiencing peripheral neuropathy greater than grade 2 (OR = 4.26, 95% CI = 1.06 to 17.11). Based on these results, we conclude that single-agent bortezomib or bortezomib based regimens as consolidation therapy after ASCT in patients with MM was effective in the improvement of PFS and response rate. However, peripheral neuropathy must be closely monitored. PMID- 26550131 TI - Glucocorticoids offer protection against myocardial injury in a murine model of sepsis. AB - Sepsis is a serious infection-related complication that, in causing significant inflammation, often leads to myocardial injury. Severe inflammation, including in sepsis, is sometimes treated with exogenous glucocorticoids (GCs). Here, to explore the potential effect of GCs to protect against myocardial injury, we created a model of sepsis in rats by performing cecal ligation and puncture (CLP) in 96 rats randomly divided into sham-operated control (N=32), untreated sepsis (CLP, N=32), and GC-treated sepsis (N=32) groups. At 3, 6, 12, and 24 h after surgery, the changes in cardiac hemodynamic indexes, serum inflammatory response factor levels, and myocardial enzymes were measured, along with mitochondrial membrane potential in myocardial cells, apoptosis of myocardial cells, and the expression of nuclear factor kappa B (NF-kappaB p65) in myocardial tissues. Pathological changes in myocardial cells were also observed. Compared to the sham operated group, CLP rats experienced deterioration of left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dP/dtmax), and the maximum rate of left ventricular pressure drop (-dP/dtmax). CLP rats also had a rise in serum tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), cardiac troponin I (cTnI), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and NF-kappaB p65 in myocardial tissues. The GCs-treated group had lower levels of these inflammatory response molecules than the CLP group, with the exception of anti-inflammatory cytokine interleukin 10 (IL-10), which was higher in the GC-treated rats than the CLP group at each time point post-surgery. Compared to the sham group, CLP rats had a rise in myocardial cell apoptosis and a drop in mitochondrial membrane potential in myocardial cells. In addition, GCs-treated rats had a marked drop in the myocardial cell apoptosis rate and a rise in the mitochondrial membrane potential compared to CLP rats. After intervention with GCs, the pathological changes in heart tissues were also reduced compared to those in the sepsis group. Based on these results, we conclude that exogenous GCs can inhibit a drop in myocardial mitochondrial membrane potential and inhibit myocardial cell apoptosis by blocking the activation of NF-kappaB, decreasing the generation of proinflammatory cytokines, and relieving inflammatory injury in heart tissues. PMID- 26550132 TI - Application research on three-dimensional ultrasonic skeletal imaging mode in detecting fetal upper jaw bone. AB - OBJECTIVE: To detect three-dimensional (3D) ultrasound appearance of fetal normal and abnormal supermaxilla bone's anatomy using skeletal rendering mode, and to compare the success rate of 3D images in different gestational age groups. METHODS: Using three-dimensional ultrasound skeletal rendering mode of voluson 730 and voluson E8 ultrasound systems, the fetal supermaxilla bones were reconstructed, the supermaxilla bones include two hundred and sixty-one cases with the range from 12 to 40 gestaional weeks that were normal supermaxilla proved by 2D ultrasound exam, three cases that were the specimens of fetal normal supermaxilla, and eight cases that were abnormal supermaxilla. The normal supermaxilla's imaging success rates of different gestational ages were contrasted. RESULTS: The success rate of normal fetal supermaxilla bone's formation and structure with the 3D image was 97.9% during the gestation of 12~15(+6) weeks, 96.0% of 16~21(+6) weeks, 98.4% of 22~27(+6) weeks, 68.6% of 28~35(+6) weeks, 27.5% of 36~40 weeks. Through the X(2) test, there was no significant difference in the success rate of displaying among the gestation of 12~15(+6) weeks, 16~21(+6) weeks and 22~27(+6) weeks. The success rate during the gestation of 36~40 weeks was the lowest among all the gestation. Big anatomic structures of fetal supermaxilla in 3D images can be shown, but detail cannot. The success rate of cleft palate with 3D image was 100% (8 cases). CONCLUSIONS: 3D ultrasound can supply more detailed and comprehensive information of fetal supermaxilla bone. The better fit examine weeks for obtaining 3D images are within 12~35(+6) weeks, the best fit examine weeks are within 16~27(+6) weeks. The function of 3D skeletal rendering mode image can display cleft palate clearly. PMID- 26550133 TI - Peroxisome proliferator-activated receptor gamma (PPARG) polymorphisms and breast cancer susceptibility: a meta-analysis. AB - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARG), a nuclear hormone receptor, plays a critical role in the lipid and glucose homeostasis, adipocyte differentiation, as well as intracellular insulin-signaling events. Several studies have been conducted to explore the associations of PPARG polymorphisms with breast cancer (BC), yet the findings are inconsistent. METHODS: Databases of Pubmed and Embase were searched until October 5, 2014. The association between PPARG polymorphisms and BC risk was determined by crude odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS: Finally, there are nine publications involving 3,931 BC cases and 5,382 controls included in this meta-analysis. No significant association was observed between PPARG rs1801282 C>G variants and overall BC risk in all genetic comparison models. However, in a subgroup analysis by ethnicity, significant association was observed between PPARG rs1801282 C>G variants and decreased BC risk in three genetic models: GG+CG vs. CC (OR, 0.83; 95% CI, 0.71-0.96; P = 0.011), CG vs. CC (OR, 0.82; 95% CI, 0.71-0.96; P = 0.011) and G vs. C (OR, 0.85; 95% CI, 0.75 0.97; P = 0.016) in Caucasians and in a subgroup analysis by menopausal status, significantly decreased BC risk was also found in two genetic models: GG+CG vs. CC (OR, 0.79; 95% CI, 0.67-0.95; P = 0.011) and CG vs. CC (OR, 0.77; 95% CI, 0.64 0.92; P = 0.005) in post-menopause subgroup. For PPARG rs3856806 C>T, we found no significant association between PPARG rs3856806 C>T polymorphism and breast cancer. CONCLUSIONS: In summary, despite some limitations, the results suggest that PPARG rs1801282 C>G polymorphism may be a protective factor for BC in Caucasians and in post-menopause women. PMID- 26550134 TI - Mesenchymal status of lymphatic endothelial cell: enlightening treatment of lymphatic malformation. AB - In contrast to blood capillaries, lymphatic capillaries in peripheral tissues are composed of a single-cell layer of lymphatic endothelial cells (LECs) without a covering of mural cells. However, in lymphatic malformations, the enlarged lymphatic vessels were covered with mural cells. This study aimed to understand the molecular mechanism of differences between human dermal lymphatic endothelial cells (HDLECs) and human umbilical vein endothelial cells (HUVECs) and to determine the changes of LECs in the pathological condition of lymphatic malformation. Results showed that HDLECs exhibited lower expression of endothelial proteins, including VE-cadherin and CD31, than HUVECs; HDLECs also showed higher expression of mesenchymal proteins, including alpha-SMA, SM22alpha, calponin, and epithelial mesenchymal transition-related transcription factor Slug, than HUVECs. Likewise, HDLECs displayed higher permeability and weaker recruitment of SMCs than HUVECs; HDLECs also exhibited low PDGF-BB expression. TGF-beta2 treatment and FGF2 depletion enhanced mesenchymal marker expression with increased permeability and reduced SMC recruitment. By contrast, Slug depletion in HDLECs enhanced VE-cadherin expression, inhibited alpha-SMA expression, decreased permeability, and enhanced PDGF-BB expression. These results suggested that HDLECs were in a mesenchymal status, which contributed to their functions and might determine their identities. Our data also revealed that miR143/145 was implicated in the mesenchymal status of HDLECs. In lymphatic malformations (LMs) treated with OK-432 sclerotherapy, immunohistochemistry results showed that Prox1 expression was reduced and mural cell investment was increased; these results indicated that LECs lost their mesenchymal status after OK-432 treatment was administered. The decreased mesenchymal status of LECs in LMs may induce dilated vessel constriction, which could be the mechanism of OK 432 sclerotherapy. PMID- 26550135 TI - Herbal compound Naoshuantong capsule attenuates retinal injury in ischemia/reperfusion rat model by inhibiting apoptosis. AB - OBJECTIVES: Ischemic ophthalmopathy threatens people's lives and health. The herbal compound medication, Naoshuantong capsule, plays a critical role in the treatment of cardiac-cerebral vascular diseases; however, the roles and mechanisms of action of Naoshuantong capsule in ischemic ophthalmopathy is unknown. The objective of the present study was to determine the effect and mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy in rats. METHODS: In this study a rat model of ischemic ophthalmopathy was constructed using a high intra-ocular pressure-induced ischemia/reperfusion model. The effects of Naoshuantong capsule on ischemic ophthalmopathy were detected using electroretinography, and changes in retinal ultrastructure were examined by HE staining and electron microscopy. The mechanism of action of Naoshuantong capsule on ischemic ophthalmopathy was explored by immunofluorescence and real-time PCR. RESULTS: Rat models of ischemic ophthalmopathy were successfully constructed by intra-ocular hypertension, which presented decreased amplitudes of the electroretinogram (ERG-b) wave and total retinal thickness, intracellular damage, increased expression of Bax and caspase 3, and decreased expression of Bcl-2. Treatment with Naoshuantong capsule attenuated the changes and damage to the ischemic retina in the rat model, inhibited the over-expression of Bax and caspase 3, and increased the expression of Bcl-2. CONCLUSION: Our study indicated that Naoshuantong capsule attenuates retinal damage in rat models of ischemic ophthalmopathy, possibly by inhibiting apoptosis. PMID- 26550136 TI - The association of three BACE1 gene polymorphisms (exon5 C/G, intron 5 T/G and 3'UTR T/A) with sporadic Alzheimer's disease susceptibility: a meta-analysis. AB - Despite biological support for a role of Beta-site APP-cleaving enzyme 1 (BACE1) in sporadic Alzheimer's disease (SAD), studies about the BACE1 genetic polymorphisms in SAD are inconsistent. To explore whether the BACE1 polymorphisms confers susceptibility to SAD, the current meta-analysis was conducted to evaluate the gene-disease association in relevant studies. The serious databases were researched to identify studies. The association between BACE1 (exon5 C/G, intron 5 T/G or 3'UTR T/A) polymorphism and SAD risk was evaluated by odds ratios (ORs) together with their 95% confidence intervals (CIs). The combined results showed no significant difference in all models on the basis of all studies for BACE1 (exon5 C/G, intron 5 T/G or 3'UTR T/A) polymorphisms. When subgroup analysis was performed based on ethnicity and the epsilon 4 allele of apolipoprotein E (APOEepsilon4) carriers status, significant associations were demonstrated (CC versus CG+GG: OR=1.37, 95% CI=1.04-1.82, P=0.03<0.05 and CC versus CG: OR=1.49, 95% CI=1.11-2.01, P=0.01<0.05) for APOEepsilon4 carriers status. The pooled results suggest the BACE1 (exon5 C/G, intron 5 T/G or 3'UTR T/A) polymorphism could be not a risk factor for SAD. However, individuals with CC genotype have higher risk of SAD with APOEepsilon4 carrier status, and gene gene interaction might affect on the association. Further studies with large sample size, especially in subgroup analysis, should be done to confirm these findings. PMID- 26550137 TI - In-vitro rescue and recovery studies of human melanoma (BLM) cell growth, adhesion and migration functions after treatment with progesterone. AB - Treatment of human melanoma (BLM) cells for 48 hrs with progesterone resulted in a significant inhibition of cell growth. The mechanism of growth inhibition was due to autophagy and this action of progesterone was not mediated through progesterone receptor. As cells were floating during treatment, adhesion assay was performed, which showed complete loss of adhesion. When cells were allowed to recover after treatment by culturing in growth medium without progesterone, there was recovery in cell growth. Preliminary experiments on adhesion and recovery cell growth prompted us to suppress autophagic lysosomal degradation with 3 methyladenine (3-MA), which resulted in partial rescue of cell growth, adhesion and migration functions. The above experimental design gave rise to two experimental groups viz., progesterone treated and 3-MA rescued. Since, recovery studies also showed improvement in cell growth, progesterone treated and 3-MA rescued groups were allowed to recover on their own for first 48 hrs and then a second 48 hrs. Comparison of in-vitro cell growth, adhesion and migration functions of progesterone treated, 3-MA rescued and recovered human melanoma cells revealed that the recovery of 3-MA rescued cells was better than the recovery of progesterone treated cells in terms of cell growth and adhesion functions. These in-vitro experiments not only provided the scientific basis for epidemiological findings that menstruating females were better protected in melanoma, but also showed the potential of progesterone to act as an anti-cancer agent for melanoma treatment. PMID- 26550138 TI - MicroRNA-18a as a promising biomarker for cancer detection: a meta-analysis. AB - Patients with cancer discovered at an early stage have relatively high survival rates. Increasing researches have shown the potential of detecting dysregulated microRNA-18a (miR-18a) to diagnose cancer. However, non-uniform results in previous studies were found. Thus, this meta-analysis was conducted to further explore the clinical applicability of miR-18a as an ideal biomarker for cancer detection. Suitable articles were obtained from online databases like PubMed, Embase, Cochrane, CBM and Wanfang. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of our meta-analysis. The pooled diagnostic parameters like specificity, sensitivity, diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and NLR) and area under the summary receiver operator characteristic curve (SROC) were pooled to assess the entire test accuracy. Overall, 10 studies from 9 articles, including 979 patients with cancer and 713 healthy controls were involved in our meta-analysis. The pooled sensitivity was 0.78 (95% CI: 0.70-0.84) and the corresponding specificity was 0.82 (95% CI: 0.73-0.89). The merged PLR was 4.3 (95% CI: 2.8 6.8), NLR was 0.27 (95% CI: 0.20-0.37), and DOR was 16 (95% CI: 8-31). The pooled AUC was 0.86 (95% CI: 0.83-0.89). Our meta-analysis suggested that miR-18a might open up a new field for novel clinical cancer screening with the merits of high accuracy, non-invasiveness, convenience and cheap cost. However, more reliable studies in larger cohort should be conducted before it is used. PMID- 26550139 TI - Expansion of CD14(+)CD16(+) monocytes is related to acute leukemia. AB - BACKGROUND: OBJECTIVE: Aim to investigate the proportion of CD14(+)CD16(+) monocytes and understand the pathogenesis of this monocyte subset in acute leukemia. METHODS: Flow cytometry was utilized to study the phenotype expression of CD14(+)CD16(+) monocytes and CD3(+) T lymphocytes in peripheral blood derived from patients with acute leukemia. All the data were analyzed by SPSS 13.0 software. RESULTS: The proportion of CD14(+)CD16(+) monocytes including both intermediate and non-classical monocytes, increased significantly in patients with acute leukemia and changed negatively or positively according to the disease process. Meanwhile, the proportion of CD14(+)CD16(+) monocytes was inversely correlated with absolute number of CD4(+) T lymphocytes, ratio of CD4(+)/CD8(+) T cells, and positively correlated with the proportion of neutrophil granulocytes. CONCLUSIONS: The proportion of CD14(+)CD16(+) monocytes (especially the intermediate subpopulation) is related to the progression of acute leukemia, and the expansion of this monocyte subset could indicate the severity of the disease. PMID- 26550140 TI - Aqueous extracts of Fructus Ligustri Lucide induce gastric carcinoma cell apoptosis and G2/M cycle arrest. AB - OBJECTIVE: Previous studies have shown that Fructus Ligustri Lucide (FLL) can be used to anti-cancer. However, the mechanism by which FLL mediate this effect is unclear. In the present study, aqueous extracts of FLL induced cell apoptosis in human gastric carcinoma cell was investigated. METHODS: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting. RESULTS: Treatment of human gastric carcinoma cells with FLL induced cell death in a dose- and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the early and terminal phase of apoptosis cells had gained after FLL treatment as compared to untreated group. Moreover, human gastric carcinoma cells were exposed to the aqueous extracts of FLL for 48 h, which resulted in an accumulation of cells in G2/M phase. Apoptotic bodies were clearly observed in human gastric carcinoma that had been treated with FLL for 48 h and then stained with Hochest 33342. Treatment of gastric carcinoma cells with increasing doses of FLL and increasing durations significantly increased the protein expression of Bax and Caspase3, decreased the anti-apoptotic Bcl-2 level. The expression of CDC2 and cdc25C were downregulated upon FLL treatment in human gastric carcinoma. In contrast, p53 and p21 were obviously upregulated by FLL treatment in a concentration-dependent manner. CONCLUSIONS: These results confirmed that FLL could induce apoptosis in human gastric carcinoma, the underlying molecular mechanisms, at least partially, through activation p21/p53 and suppression CDC2/cdc25C signaling in vitro. PMID- 26550141 TI - MicroRNAs level as an initial screening method for early-stage lung cancer: a bivariate diagnostic random-effects meta-analysis. AB - Accumulating studies suggested that microRNAs (miRNAs) can have high diagnostic value as a non-invasive and cost-effective procedure with high sensitivity and specificity in the detection of early-stage lung cancer. However, there is inconsistency observed in the results of relevant studies. Therefore, we performed this meta-analysis to evaluate diagnostic value of miRNAs based on all related studies. A total of 38 studies from 13 included articles were used for the analysis, consisting of 510 patients and 465 healthy controls. All analyses were performed on the R 3.2.0 software. The bivariate random-effects meta analysis model was applied to obtain the following pooled parameters: sensitivity, 0.797 (95% CI: 0.756-0.832); false positive rate, 0.296 (95% CI: 0.250-0.346); and AUC, 0.818. In addition, subgroup analyses were conducted, showing not only that a combination of multiple miRNAs as biomarkers have greater diagnostic value for early-stage lung cancer (sensitivity, false positive rate and AUC of 83%, 25.2% and 0.858, respectively) had a higher diagnostic accuracy than single miRNA (sensitivity, false positive rate and AUC of 78.3%, 31.6% and 0.799, respectively), but also that specimen from circulating system (sensitivity, false positive rate and AUC of 82.5%, 30.5% and 0.836, respectively) provide better biomarkers than specimen from non-circulating system (sensitivity, false positive rate and AUC of 73.8%, 26.5% and 0.796, respectively). In summary, the current meta-analysis suggests that miRNAs as biomarkers, particularly a combination of multiple tumor-specific miRNAs from circulating system, have moderately high clinical diagnostic value in the detection of early-stage lung cancer. However, the clinical diagnostic utilization and additional improvements of miRNAs as biomarkers for early-stage lung cancer detection still remain to be further validated by more future studies. PMID- 26550142 TI - The study of energy metabolism in bladder cancer cells in co-culture conditions using a microfluidic chip. AB - OBJECTIVES: This study aimed to systematically analyze changes in mitochondrial related protein expression in bladder cancer cells and tumor-associated fibroblasts and to investigate the characteristics of bladder cancer cell energy metabolism. METHODS: In this study, we utilized the following techniques to achieve the objectives: (1) a co-culture system of bladder tumor cells and fibroblasts was built using a microfluidic chip as a three-dimensional culture system; (2) the concentration of lactic acid in the medium from the different groups was determined using an automatic micro-plate reader; (3) a qualitative analysis of mitochondria-related protein expression was performed by immunofluorescent staining; and (4) a quantitative analysis of mitochondrial associated protein expression was conducted via Western blot. SPSS software was utilized to analyze the data. RESULTS: (1) Determination of lactic acid concentration: The lactic acid concentration was determined to be highest in the experimental group, followed by the T24 cell control group and then the fibroblast control group. (2) Qualitative results: In the control group, the mitochondrial-related protein fluorescence intensity was higher in the fibroblasts compared with the cancer cells, and the fluorescence intensity of the fibroblasts was reduced compared with the experimental group. The mitochondrial related protein fluorescence intensity of the cancer cells was higher in the experimental group compared with the control group, and the opposite results were obtained with the fibroblasts. (3) Quantitative results: The expression of mitochondria-related proteins was higher in fibroblasts compared with cancer cells in the control group, and the opposite results were obtained in the experimental group (P<0.05). The expression of mitochondria-related proteins was increased in cancer cells in the experimental group compared with the control group; the opposite results were observed for the fibroblasts (P<0.05). CONCLUSIONS: The energy metabolism of bladder tumor cells does not parallel the "Warburg effect" because even under sufficient oxygen conditions, cancer cells still undergo glycolysis. Bladder cancer cells also have an efficient oxidative phosphorylation process wherein cancer cells promote glycolysis in adjacent interstitial cells, thereby causing increased formation of nutritional precursors. These high-energy metabolites are transferred to adjacent tumor cells in a specified direction and enter the Krebs Cycle. Ultimately, oxidative phosphorylation increases, and sufficient ATP is produced. PMID- 26550143 TI - Curculigoside regulates proliferation, differentiation, and pro-inflammatory cytokines levels in dexamethasone-induced rat calvarial osteoblasts. AB - BACKGROUND: Curculigoside (CCG), one of the main bioactive phenolic compounds isolated from the rhizome of Curculigo orchioides Gaertn., is reported to prevent bone loss in ovariectomized rats. However, the underlying molecular mechanisms are largely unknown. Therefore, we investigated the effects of CCG on proliferation and differentiation of calvarial osteoblasts and discussed the related mechanisms. MATERIALS AND METHODS: Osteoblasts were incubated with dexamethasone (DEX) in the absence or presence of CCG concentrations for 24-72 h. Cell proliferation was evaluated by Cell Counting Kit-8 assay. Mitochondria membrane potential (MMP) and reactive oxygen species (ROS) were assessed by flow cytometry. We assessed the anti-inflammatory responses of CCG on DEX-induced osteoblasts by an enzyme-linked immunosorbent assay (ELISA). Relative protein expression of BMP-2, b-catenin, RANKL, OPG and RANK was measured using Western blotting. RESULTS: It was found that osteoblasts proliferation decreased significantly after treated with 1 MUM of dexamethasone (DEX), compared with untreated osteoblasts and the cytotoxic effect of DEX was reversed remarkably when pretreatment with 25-100 MUg/ml of CCG. Pretreatment with 25-100 MUg/ml of CCG increased MMP level and decreased ROS production in osteoblasts induced by DEX. In addition, DEX-induced inhibition of differentiation markers such as alkaline phosphatase (ALP), OPG, BMP-2, beta-catenin, IGF-1 and M-CSF level, and promotion of differentiation markers such as RANKL and RANK was significantly reversed in the presence of CCG. CCG also reversed DEX-induced production of pro inflammatory cytokines. CONCLUSIONS: These results provide new insights into the osteoblast-protective mechanisms of CCG through inducing proliferation and differentiation and reducing the inflammatory responses, indicating that CCG may be developed as an agent for the prevention and treatment of osteoporosis. PMID- 26549981 TI - ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider. AB - This paper reviews and extends searches for the direct pair production of the scalar supersymmetric partners of the top and bottom quarks in proton-proton collisions collected by the ATLAS collaboration during the LHC Run 1. Most of the analyses use 20 [Formula: see text] of collisions at a centre-of-mass energy of [Formula: see text] TeV, although in some case an additional [Formula: see text] of collision data at [Formula: see text] TeV are used. New analyses are introduced to improve the sensitivity to specific regions of the model parameter space. Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models. PMID- 26550144 TI - Lowering blood ammonia prevents hepatocyte injury and apoptosis. AB - To study hepatocyte injure through establishing the rat model of acute hepatic failure (ALF). ALF rat model was established by administration with D galactosamine and LPS, and then giving lowering blood ammonia (LBA) treatment. Besides, the intervention groups were injected with ornithine and aspartate. The control groups were injected saline. Blood ammonia, ALT, AST, TNF-alpha and IL-6 in blood samples were test at 12 hrs and 24 hrs after treatment with LBA. Hepatocyte apoptosis were tested by TUNEL and DNA Ladder. Expression of P53 and SPP1 were detected by RT-PCR. RESULTS: showed that blood ammonia in hepatic failure group and intervention group compared with blank control group was significantly increased at 12 h, 24 h; intervention group compared with hepatic failure group was significantly reduced (P<0.05). Serum ALT, AST in 24 h group were higher than 12 h. 12 h intervention group was decreased compared with hepatic failure group, but there was no significant statistically difference (P>0.05). 24 h intervention group compared with hepatic failure group was significantly reduced (P<0.05). Except the control group, DNA ladder and the TUNEL results showed hepatocyte apoptosis rate increased in 24 h compared with 12 h. Intervention group compared with hepatic failure group was significantly reducing (P<0.05). IL-6, TNF-alpha, p53 expression levels were increased with time (24 h>12 h). The hepatic failure and intervention group compared with blank control group was significantly increased; Intervention group compared with hepatic failure group was significantly reducing (P<0.05). SPP1 gene was high expression in ALF rat model. SPP1 level in hepatic failure and intervention group compared with control group was significantly increased, and intervention group compared with hepatic failure group was significantly reducing (P<0.05). In conclusion, hepatocyte apoptosis is an important pathological change in ALF rat mode, and lowing ammonia can reduce liver injury and apoptosis. Blood TNF-alpha, IL-6 and SPP1 may be more sensitive injure indicators. PMID- 26550145 TI - Modified and systematically-designed installation procedure for spinal cord stimulation in the decubitus position under local anesthesia: a introductory technical case report. AB - INTRODUCTION: Spinal cord stimulation (SCS) is sometimes preferable in some refractory chronic lower back pain (LBP) pathologies. SCS involves an insertion of electrode leads into the epidural space in the prone position under local anesthesia, followed by neurostimulator implantation under local/general anesthesia. These continuous procedures can cause transient post-operative LBP exacerbation and to make temporary pockets that will store redundant leads in it with some risk of subcutaneous irritation and infection in addition to making extra incisions. We introduce a modified simpler method for SCS implantation, systematically designed to be performed only under local anesthesia in a decubitus, non-prone position. MATERIALS AND METHODS: An 81-year-old patient with FBSS was treated. A physician was able to insert SCS leads with ease while the patient was in a decubitus position. The patient was comfortable, under totally local anesthesia, and the procedure produced no extra subcutaneous pockets. RESULT: The patient felt almost no LBP and reported no pain exacerbation during the operation. The SCS installation provided the patient with great improvement in both her lower back (NRS from 8 to 0-1) and leg (from 7 to 2) pain with a great improvement in her daily life activities. No adverse events were observed during the perioperative period. CONCLUSION: The modified SCS insertion method enabled us to achieve both intraoperative pain relief and complete SCS implantation in a minimally invasive manner. PMID- 26550146 TI - Arachidonic acid attenuates learning and memory dysfunction induced by repeated isoflurane anesthesia in rats. AB - This study aims to explore the effects of arachidonic acid (ARA) on learning and memory dysfunction in rats exposed to repeated isoflurane anesthesia and the underlying mechanisms. Fifty rats were randomly divided into five groups: sham control group, isoflurane group, low dose ARA + isoflurane group, moderate dose ARA + isoflurane group, high dose ARA + isoflurane group. The Morris water maze test was performed to assess learning and memory function and the hippocampus tissues were obtained for biochemical analysis. The results showed that administration of ARA improved learning and memory deficit induced by repeated isofluane anesthesia in Morris water maze test and in a dose-dependent manner. Additionally, ARA increased the activities of choline acetyl transferase (ChAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of acetycholine (Ach) and gamma-amino-butyric acid (GABA), whereas decreased the activity of acetylcholine esterase (AchE), the content of glutamate (Glu) and malondialdehyde (MDA), and the radio of Glu/GABA. Meanwhile, ARA elevated the ratio of Bcl-2/Bax and inhibited the activity of caspase-3. In conclusion, ARA has potential therapeutic value in alleviating isoflurane-induced learning and memory impairment. The mechanism might be involved in regulating the cholinergic and Glu/GABA regulatory system, decreasing oxidative damage and inhibiting cell apoptosis. PMID- 26550147 TI - Andrographolide plays an important role in bleomycin-induced pulmonary fibrosis treatment. AB - Pulmonary fibrosis (PF) leads to chronic inflammation and accumulation of macrophages, neutrophils, and lymphocytes in the alveoli. The factors involved in the development of PF include reactive oxygen species and tissue remodelling regulators. The present study demonstrates the effect of andrographolide on bleomycin (BLM)-induced PF in Sprague-Dawley rats. We investigated the total bronchoalveolar lavage fluid protein (BALF) and hydroxyproline (HYP) content along with the level of oxidative stress markers like malondialdehyde (MDA) and GSH/GSSG ratio. In addition, the levels of MMP-1 and TIMP-1 were also analysed. The results revealed an increase in BALF protein, HYP, and MDA contents and decrease in GSH/GSSG ratio of the lungs in animals treated with BLM. However, andrographolide treatment caused a reversal of the BLM induced changes after 20 or 40 days. Treatment with andrographolide suppressed oxidative stress with the decrease of MDA and the increase of the GSH/GSSG ratio. Andrographolide also improved the BLM mediated changes in the MMP-1/TIMP-1 ratio. Therefore, andrographolide has a potential therapeutic effect in the prevention of PF. PMID- 26550151 TI - Study on encapsulation of chlorine dioxide in gelatin microsphere for reducing release rate. AB - OBJECTIVE: This study aims to explore the effects of encapsulation of chlorine dioxide in a hydrophilic biodegradable polymer gelatin to reduce its release rate. METHODS: An emulsification-coacervation method was adopted. The characterizations of chlorine dioxide-gelatin microspheres were described. Using UV-vis spectrophotometer the lambdamax of chlorine dioxide was observed at 358 nm. The particle size and distribution of chlorine oxide-gelatin microspheres was measured by a dynamic light scattering (DLS) method, the diameter was (1400~1900) nm. The entrapment of chlorine dioxide-gelatin microspheres was confirmed by IR. The surface morphology, size, and shape of chlorine dioxide-gelatin microspheres were analyzed using Scanning electron microscope (SEM). RESULTS: It showed that the encapsulated microspheres size was around 2000 nm with uniform distribution. The percentage entrapment of chlorine dioxide in the encapsulated samples was about 80~85%. A slow release study of chlorine dioxide from the encapsulated biopolymer (gelatin) in air was also carried out, which showed continuous release up to ten days. CONCLUSIONS: It can be concluded that it is possible to make a slow release formulation of ClO2 by entrapped in a hydrophilic biodegradable polymer gelatin. ClO2-gelatin microspheres can stable release low concentration ClO2 gas over an extended period. PMID- 26550148 TI - Anti-inflammatory effect of emodin on lipopolysaccharide-induced keratitis in Wistar rats. AB - Emodin, a major bioactive extract of several Chinese herbs, has been shown to have a number of biological activities including antiviral, anti-inflammatory, anti-tumor, anti-fibrosis etc. In the present study, we investigated the effects of emodin as an anti-inflammatory agent on lipopolysaccharide (LPS) induced keratitis in Wistar rats. Clinical score, slit-lamp microscope were used to determine corneal inflammatory response. Corneal structure was observed by hematoxylin-eosin staining and transmission electron microscopy. Messenger ribonucleic acid levels of tight junction protein and cytokines were determined by reverse transcription- polymerase chain reaction. The activation of nuclear factor-kappa B (NF-kappaB) was detected with Western blot. We found that disorganized corneal tissue and cellular structures were observed in keratitis rats and emodin could deduce inflammatory response and improve corneal structure. Pretreated with emodin could up-regulate and down-regulate the mRNA expression of occludin and Interleukin-6. The activation of NF-kappaB could be inhibited partly after emodin treatment. In conclusion, emodin reduced corneal inflammation in LPS induced keratitis in Wistar rats due to its capability of inhibition in NF-kappaB activation. PMID- 26550149 TI - Effects of calcitriol on structural changes of kidney in C57BL/6J mouse model. AB - Thisaim of the studyisto investigate the effects of calcitriol (vitamin D) on mouse kidneys under obese conditions. Male C57BL/6J mice were maintained on either low fat diet (LFD) or high fat diet (HFD) with/without calcitriol treatment (150 IU/kg/day) for 16 consecutive weeks. Results of HFD fed mice demonstrated more weight gain and showed numerous structural abnormalities in the corticomedullary region compared to those under control and LFD conditions. Near nephropathy condition in HFD mice were characterized by damage in renal tubules, including dilatation of interstitial cells and blood vessels. Furthermore, exfoliation and shedding of proximal tubular cells takes place. The conditions further worsen by thickening the basement membrane and interstitial inflammation, as evidenced by abundant interstitial debris. Additionally, a large number of degenerated mitochondria, fat droplets, lysosomal bodies' mesangial expansion, and cellular debris were found throughout the kidney. Sustained cell hypertrophy was also evident by transmission electron microscope confirming a marked increase in degeneration of cells within renal areas. No significant variances were detected in the glomerulus' area and diameter in both low and high fat diets with/without calcitriol treatment as well as inner and outer diameters of both distal and proximal tubule in all groups. Evidently, calcitriolcould act as a protective agent to normalize kidney structure in obese condition. This study suggests that calcitriol could normalize the function of kidney and protect its structural integrity in obesity. PMID- 26550150 TI - MicroRNA 192 regulates chemo-resistance of lung adenocarcinoma for gemcitabine and cisplatin combined therapy by targeting Bcl-2. AB - Lung cancer is the most leading cause of cancer-related death worldwide, with non small-cell lung cancer (NSCLC) accounting for over 80% of all lung cancer cases. Patients with NSCLC are mostly treated with platinum-based chemotherapy. Chemoresistance is a leading cause of chemo-therapy failure in NSCLC treatment. Recent studies have shown that dysregulation of microRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. In this paper, we try to test whether miR-192 regulates chemo-resistance in human carcinoma A549 mice model by targeting Bcl-2. Mice model of human lung adenocarcinoma was built up, and was used for gemcitabine and cisplatin combined chemotherapy. MTT assay, real-time RT-PCR, western blotting assay were used to investigate miR-192 expression levels, cell viability ratio and Bcl-2 protein expression levels. MiR-192 expression level in A549 cells is significantly higher than in normal human bronchial epithelial cells. MiR-192 inhibitor treated tumor exhibits sensitivity to cisplatin and gemcitabine therapy. Bcl-2 mRNA and protein expression levels up-regulated in miR-192 inhibitor treated tumor. Bcl-2 is a key regulator for miR-192 related chemotherapy resistance. In this study, we demonstrate that miR-192 regulates chemoresistance for gemcitabine and cisplatin combined chemotherapy in human adenocarcinoma lung cancer A549 cells, and Bcl-2 is the target of miR-192. PMID- 26550152 TI - VEGF silencing inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via PI3K/AKT signaling pathway. AB - Vascular endothelial growth factor (VEGF) is one of the most potently angiogenic factors which promotes generation of tumor vasculature. VEGF is usually up regulated in multiple cancers include osteosarcoma and gliomas. To further explore the potential molecular mechanism that inhibits tumor growth induced by interference of VEGF expression, we constructed an Lv-shVEGF vector and assessed the efficiency of VEGF silencing and its influence on U2OS cells. Our data demonstrated that Lv-shVEGF has high inhibition efficiency on VEGF expression, which inhibits proliferation and promotes apoptosis of U2OS cells in vitro. Our results also indicated that inhibition of VEGF expression suppresses osteosarcoma tumor growth in vivo, VEGF inhibition reduces osteosarcoma angiogenesis. We also found that the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) activation was considerably reduced after osteosarcoma cells were treated with Lv shVEGF. Taken together, our data demonstrated that VEGF silencing suppresses cells proliferation, promotes cells apoptosis and reduces osteosarcoma angiogenesis through inactivation of PI3K/AKT signaling pathway. PMID- 26550153 TI - A comparison of oral squamous cell carcinoma between young and old patients in a single medical center in China. AB - PURPOSE: There is no consensus regarding the clinical course and prognosis for oral squamous cell carcinoma (SCC) in young patients. In this study, we report our experience with the management of oral squamous cell carcinoma, with a special focus on patients younger than 40 years old. METHODS: From 2005 to 2012, all patients were treated for oral (gingiva, the anterior 2/3 of tongue, floor of the mouth and buccal) SCC in our medical center were enrolled. RESULTS: We enrolled 430 patients, of whom 31 (7.2%) patients (19 male and 12 female) were younger than 40 years. Among the patients under 40, tumors were most commonly found on the tongue (15; 48.4%); there was recurrence in 10 (52.6%) male patients, and six (31.6%) male patients died of disease; and there was recurrence in seven (58.3%) female patients, while three (25.0%) female patients died of disease. In young patients with tongue carcinoma, five (33.3%) died of the disease and four (25%) young patients with carcinoma at other sites died of the disease. The older (>40 years old) patient group had similar rates of recurrence free survival and disease-specific survival to the young (<40 years old) patient group. CONCLUSION: In the young group, patients with tongue carcinoma tended to have a poorer prognosis than patients with carcinoma at other sites. The clinical course and prognosis were similar between the two groups, but younger patients were more likely to have a recurrence. PMID- 26550154 TI - Inhibitory effect of trichostatin on allograft rejection of corneal transplantation in rats. AB - BACKGROUND: Using a rat penetrating keratoplasty model, this study aims to explore the inhibitory effect of hachimycin on corneal graft rejection, to provide new basis for its clinical application. MATERIALS AND METHODS: Female adult Sprague-Dawley (SD) rats weighing between 220-250 g were used as acceptors and male or female Wistar rats weighing between 220-250 g were used as donors. The rats with a successful keratoplasty were randomly divided into 3 groups with 10 rats in each group. Group A: penetrating keratoplasty group; Group B: penetrating keratoplasty followed by the application of control eye drops containing eye drops matrix dissolved in 20 g/L DMSO and 900 mL/L artificial tear; Group C: penetrating keratoplasty followed by the application of 0.5 g/L hachimycin eye drops. Hachimycin was dissolved in vitamin E to obtain an eye solution with a pH value of 6~7, and stored at 4 degrees C. The local application of hachimycin eye drops started 5 days after the keratoplasty surgery, 5 times per day until the onset of rejection response. At 4 days after the keratoplasty surgery, slit-lamp microscope was used to observe the transplanted cornea once every two days, and a rejection index (RI) of 0-12 was obtained according to the three graft components represented by corneal transparency, edema, and corneal neovascularization. RESULTS: Penetrating keratoplasty was successfully performed on all the 3 groups of rats. Five days after the keratoplasty, both the transparency and the implant edema showed a score of 1-2 degrees in group A and B. Two weeks later, both these two grafts components increased to a score of 2-3 degrees in group A and B, with an active neovascularization. The group C also showed a transparency and implant edema of 1-2 degrees five days after the keratoplasty surgery. However, a transparent implant without edema was observed in group C two weeks after the keratoplasty surgery. In addition, the newly formed blood vessels disappeared and the retina appeared in a good status and in the correct position. The corneal transparency, edema, corneal neovascularization, and total RI scores of the 3 groups clearly indicated that the group B showed an improvement compared to the group A (P < 0.05), since in group B the new vessels were only distributed in the corneal limbus at five days after the surgery. However, at two weeks after the surgery no statistically significant difference in neovascularization degree was observed in group B when compared with group A, while a statistically significant decrease of neovascularization was observed in group C (P < 0.05). CONCLUSIONS: Hachimycin may inhibit the rejection responses after penetrating keratoplasty by the reduction of corneal edema, transparency and neovascularization. PMID- 26550155 TI - Association of glutathione S-transferase T1, M1 and P1 polymorphisms in the breast cancer risk: a meta-analysis in Asian population. AB - BACKGROUND: Published data regarding the associations between glutathione S transferase (GST) T1, M1 and P1 polymorphisms and breast cancer risk are inconclusive. The aim of this study is to comprehensively evaluate the genetic risk of GST genes for breast cancer. MATERIALS AND METHODS: A systematic literature search was carried out in Pubmed, Medline (Ovid), Embase, CBM, CNKI, Weipu, and Wanfang database, covering all publications (last search was performed on May 20, 2015). Statistical analysis was performed using Revman 5.2 and STATA 12.0 softwares. RESULTS: A total of 12,035 cases and 13,911 controls in 34 case control studies were included in this meta-analysis. The results suggested that the GSTM1 and GSTP1 polymorphisms can obviously increase the risk of breast cancer in Asian population (odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.04-1.33, P = 0.008 and OR = 1.23, 95% CI = 1.07-1.41, P = 0.003, respectively), especially in East Asian (OR = 1.14, 95% CI = 1.01-1.27, P = 0.03 and OR = 1.15, 95% CI = 1.03-1.28, P = 0.01, respectively) and hospital-based case-control study (HCC) group (OR = 1.32, 95% CI = 1.11-1.56, P = 0.001 and OR = 1.38, 95% CI = 1.03-1.84, P = 0.03, respectively), while the association between GSTT1 null genotype and breast cancer risk is not significant (OR = 1.08, 95% CI = 0.93-1.25, P = 0.3). CONCLUSIONS: This meta-analysis indicated that the GSTM1 and GSTP1 polymorphisms might significantly contribute to breast cancer susceptibility in Asian population, especially in East Asian, while the GSTT1 polymorphism might not be associated with breast cancer. PMID- 26550156 TI - Cyclooxygenase-2 -1195G>A (rs689466) polymorphism and cancer susceptibility: an updated meta-analysis involving 50,672 subjects. AB - The association between cyclooxygenase-2 (COX-2) -1195G>A (rs689466) polymorphism and cancer risk has been extensively explored. However, the results of previous studies remain controversial. To address this gap, we performed an updated meta analysis of fifty-eight studies involving a total of 50,672 subjects. Searching of PubMed and Embase databases was performed for publications on the association between COX-2 -1195G>A polymorphism and the risk of cancer. Statistical correlation was identified between COX-2 -1195G>A variants and overall cancer risk in five genetic models. In a sub-group analysis based on cancer type, significant association between COX-2 -1195G>A polymorphism and increased risk of gastric cancer, pancreatic cancer, hepatocellular carcinoma and other cancers was found. In a sub-group analysis by ethnicity, increased cancer risk was observed among Asians instead of Caucasians, Africans and mixed populations. Furthermore, in a sub-group analysis based on cancer system, increased cancer risk was found in digestive system cancer and other system cancer. Non-parametric "trim-and fill" method was harnessed as a sensitivity analysis method and the results suggested our findings reliable. In summary, the results of our meta-analysis highlight that COX-2 -1195G>A polymorphism may be a risk factor for cancer. PMID- 26550157 TI - Severe pneumonia in the elderly: a multivariate analysis of risk factors. AB - Pneumonia is the second leading reason for hospitalization of medicare beneficiaries. The mortality rate is high, especially in the elderly. In this study, we aimed to determine the risk factors associated with severe pneumonia in the elderly. Retrospective study was conducted and data of old patients with severe pneumonia were collected. They were divided into two groups: the experiment group (death group) and the control (living group). The general situation, underlying diseases, laboratory tests, types of etiology, imaging analysis and treatment situation of patients were analyzed and compared. Univariate analysis and logistic multivariate regression analysis were used to screen the related and independent risk factors for the diagnosis of severe pneumonia in the elderly. In univariate analysis, there were many factors had statistical significance including chronic kidney disease, electrolyte disturbance, low phosphorus and so on. Result of logistic multivariate regression analysis showed pro-BNP level and serum prealbumin were independent risk factors. In sputum culture, the relevance ratio of acinetobacter baumannii was the highest in gram negative bacteria followed by klebsiella pneumoniae. In gram positive bacteria, the relevance ratio of staphylococcus aureus was the highest. In conclusion, the analysis on risk factors for severe pneumonia has great clinical significance on improving the prognosis. PMID- 26550158 TI - Clusterin silencing sensitizes pancreatic cancer MIA-PaCa-2 cells to gmcitabine via regulation of NF-kB/Bcl-2 signaling. AB - Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. Our recent study has demonstrated that knockdown of clusterin sensitizes pancreatic cancer cell lines to gmcitabine treatment. However the details of this survival mechanism remain undefined. Of the various downstream targets of CLU, we examined activation of the NF-kB transcription factor and subsequent transcriptional regulation of BCL-2 gene in pancreatic cancer cell MIA-PaCa-2. The MIA-PaCa-2 cells were transfected with an antisense oligonucleotide (ASO) against clusterin, which led to a decreased protein level of the antiapoptotic gene BCL-2. Furthermore, inhibition of CLU decreased the function of NF-kB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway increased the apoptotic effect of gmcitabine chemotherapy. Re-activated NF-kB resulted in attenuation of ASO induced effects, followed by the bcl-2 upregulation, and bcl-2 re-inhibition resulted in attenuation of Re-activated NF-kB -induced effects. Animals injected with ASO CLU in MIA-PaCa-2 cells combined with gmcitabine treatment had fewer tumors than gmcitabine or ASO CLU alone. These findings suggest that knockdown of CLU sensitized MIA-PaCa-2 cells to gmcitabine chemotherapy through modulating NF Kb/bcl-2 pathway. PMID- 26550159 TI - The radioprotective effects of Moringa oleifera against mobile phone electromagnetic radiation-induced infertility in rats. AB - The present study has investigated the effects of mobile phone electromagnetic radiation (EMR) on fertility in rats. The purpose of this study was to explore the capability of polyphenolic-rich Moringa oleifera leaf extract in protecting rat testis against EMR-induced impairments based on evaluation of sperm count, viability, motility, sperm cell morphology, anti-oxidants (SOD & CAT), oxidative stress marker, testis tissue histopathology and PCNA immunohistochemistry. The sample consisted of sixty male Wistar rats which were divided into four equal groups. The first group (the control) received only standard diet while the second group was supplemented daily and for eight weeks with 200 mg/kg aqueous extract of Moringa leaves. The third group was exposed to 900 MHz fields for one hour a day and for (7) days a week. As for the fourth group, it was exposed to mobile phone radiation and received the Moringa extract. The results showed that the EMR treated group exhibited a significantly decrease sperm parameters. Furthermore, concurrent exposure to EMR and treated with MOE significantly enhanced the sperm parameters. However, histological results in EMR group showed irregular seminiferous tubules, few spermatogonia, giant multinucleated cells, degenerated spermatozoa and the number of Leydig cells was significantly reduced. PCNA labeling indices were significant in EMR group versus the control group. Also, EMR affects spermatogenesis and causes to apoptosis due to the heat and other stress-related EMR in testis tissue. This study concludes that chronic exposure to EMR marked testicular injury which can be prevented by Moringa oleifera leaf extract. PMID- 26550160 TI - IL-8 up-regulates proliferative angiogenesis in ischemic myocardium in rabbits through phosphorylation of Akt/GSK-3beta(ser9) dependent pathways. AB - BACKGROUND: Therapeutic myocardial angiogenesis is an important compensatory mechanism in severely coronary stenosis. Previous studies demonstrated that interleukin-8 (IL-8) not only plays an important role in inflammation, but also a potent angiogenic factor through p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-kappaB (NK-kappaB)-dependent pathway in carcinoma. Our study sought to investigate the effects of IL-8 on the angiogenesis and the underlying mechanism in the ischemic myocardium. METHODS: Acute myocardial infarction animal model was established with male rabbits by directly suturing the left anterior descending branch, then lentivirus-mediated IL-8 was quarterly injected into the borderline of infarction area immediately. We employed CoCl2 induced hypoxic HUVECs for in vitro ischemia study. Left ventricular end-diastolic diameter (LVEDd) and ejection fraction (EF) were measured by echocardiography in pre operation and at 6(th) week after operation. CD34 was detected with immunohistochemisty to analyse angiogenesis. Western blot was performed with regard to IL-8, protein kinase B (PKB/Akt) and Glycogen synthase kinase 3beta(ser9) (GSK-3beta(ser9)). For the HUVECs' proliferation and apoptosis, multiscan spectrum reader at A570 nm and annexin V-FITC/PI staining method were used respectively. RESULTS: The levels of IL-8, phosphorylated Akt and GSK 3beta(ser9) in focal myocardium significantly increased, and the over expression of IL-8 led to an increasing in angiogenesis in rabbits. Hypoxia inhibited cell proliferation and promoted apoptosis. IL-8 induced cell proliferation, phosphorylation of Akt and GSK-3beta(ser9), inhibited apoptosis and Caspase3 expression in HUVECs, which were attenuated by anti-IL-8 or the Akt inhibitor LY294002. CONCLUSIONS: The present results indicate that IL-8 can increase angiogenesis in myocardial infarction, which maybe through enhancing Akt and GSK 3beta(ser9) expression, and inhibiting myocardial apoptosis. PMID- 26550161 TI - Adenovirus expressing IFN-lambda (Ad/hIFN-lambda) produced anti-tumor effects through inducing apoptosis in human tongue squamous cell carcinoma cell. AB - OBJECTIVE: To investigate the potential therapeutic effects of adenovirus expressing IFN-lambda1 and IFN-lambda2 (Ad/hIFN-lambda) in treating squamous cell carcinoma of the oral tongue (SCCOT) and to explore the underlying mechanisms. METHODS: Two SCCOT cell lines HSC-3 and Tca8113 were adopted as study objects. Cell Counting Kit-8 (CCK-8) cell proliferation and viability assay was performed to evaluate the antiproliferative effects of Ad/hIFN-lambda and IFN-lambda treatments at different dosages. Flow cytometry (FCM) was performed to investigate the apoptosis rate induced by Ad/hIFN-lambda. In vivo study was performed through evaluating tumorigenicity and tumor volume on BALB/c nu/nu mice inoculated with HSC-3 cells with or without infection of Ad/hIFN-lambda. qPCR was used to screen important apoptosis related genes expression and western blot (WB) was performed to verify the results. WB was also used to test the phosphorylation of STATs protein in the JAK/STAT signaling pathways. RESULTS: Our results indicated an obvious antiproliferative effect of Ad/hIFN-lambda in vitro on infected HSC-3 and Tca8113 cells. The antiproliferative effects started to appear at 48 h (day 2) after infection. IFN-lambdas alone treating HSC-3 and Tca8113 cells also showed a dose-dependent inhibitory manner. Though the antiproliferative effects did not show on 24 h (day 1), early apoptosis rate already increased significantly in cells infected with Ad/hIFN-lambda (P<0.05) detected by FCM. The underlying mechanisms of antiproliferative activity rely on the IFN-lambda signaling by phosphorylation of STATs protein. Expression of Bax, Bcl-2 and Caspase-3 were promoted by Ad/hIFN-lambda leading to higher apoptosis rate. Upper stream of p21 and Rb dephosphorylation explained the Caspase-3 activation. Animal study showed that HSC-3 cells infected with Ad/hIFN-lambda significantly promoted the survival rate and decreased mean tumor volume comparing to HSC-3 cells group. CONCLUSION: Ad/hIFN-lambda injection had obvious antiproliferative effects on HSC-3 and Tca8113 cells. Ad/hIFN-lambda induced apoptosis in SCCOT cells through increasing Bcl-2, Bax and Caspase-3 expression. Ad/hIFN-lambda is a potential therapeutic strategy in treating oral tongue carcinoma. PMID- 26550162 TI - NOD1 agonist iE-DAP reverses effects of cigarette smoke extract on NOD1 signal pathway in human oral mucosal epithelial cells. AB - Smoking is a well-known risk factor for many systemic diseases and oral disorders. Smoking has been recognized to cause diminished defense, persistent inflammation and result in disease development. Nucleotide binding oligomerization domain 1 (NOD1) signal pathway plays a key role in innate immune and tissue homeostasis. Our recent studies confirmed that cigarette smoke extract (CSE) could inhibit NOD1 expression and affect expression levels of crucial molecules of NOD1 signaling in oral mucosal epithelial cells. In the present study, immortalized human oral mucosal epithelial (Leuk-1) cells were treated with CSE, iE-DAP (NOD1 agonist), CSE + iE-DAP, respectively. Western blotting analysis demonstrated that iE-DAP triggered NOD1 expression of leuk-1 cells in a dose-dependent manner. iE-DAP also reversed the suppressive effect of CSE on NOD1 expression and prevented the overactivation of RIP2 and P-NF-kappaB following CSE exposure. Real-time PCR and ELISA results confirmed that iE-DAP reversed CSE mediated effects on the mRNA levels and releases of IL-6, IL-8, TNF-alpha and IFN gamma by Leuk-1 cells. Taken together, our results indicated that NOD1 activation with iE-DAP could reverse CSE-mediated effects on NOD1 signaling in human oral mucosal epithelial cells. PMID- 26550163 TI - Association of homocysteine with type 1 diabetes mellitus: a meta-analysis. AB - PURPOSE: To figure out the association between plasma Hcy status and type 1 diabetes mellitus (T1DM). METHODS: We searched the PubMed Web of Science, and The Cochrane Library to identify eligible studies. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of selected studies. All analyses were performed using the STATA, version 12 software. RESULTS: 15 studies were included in this investigation. Our meta-analysis indicated that plasma Hcy concentrations in T1DM patients without any complications were normal compared with healthy people [13 studies, SMD: -0.08, 95% confidence interval (CI): -0.44 to 0.28, P=0.67]. However, a significant elevation of plasma Hcy concentrations was observed in T1DM patients with only diabetic retinopathy (DR) (5 studies, SMD: 0.34, 95% CI: 0.13 to 0.55, P=0.002), only diabetic nephropathy (DN) (4 studies, SMD: 0.76, 95% CI: 0.18 to 1.33, P=0.01) and both the two complications (3 studies, SMD: 1.05, 95% CI: 0.03 to 2.07, P=0.043) compared with T1DM patients without any complications. CONCLUSIONS: Homocysteine levels elevate in T1DM patients with DR and DN, but don't elevate in T1DM without any complications. PMID- 26550164 TI - Notch1/3 and p53/p21 are a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines. AB - OBJECTIVE: Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway. METHODS: The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively. RESULTS: The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell. CONCLUSIONS: This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines. PMID- 26550165 TI - Comparisons of negative pressure wound therapy and ultrasonic debridement for diabetic foot ulcers: a network meta-analysis. AB - OBJECTIVE: a network meta-analysis was performed to compare the strength and weakness of negative pressure wound therapy (NPWT) with ultrasound debridement (UD) as for diabetic foot ulcers (DFU). METHODS: PubMed, Ovid EMBASE, Web of Science, Cochrane library databases, and Chinese Biomedical Literature Database were searched till February 2015. Clinical compared studies of negative pressure wound therapy and ultrasound debridement were enrolled. The primary efficacy outcomes included healed ulcers, reduction of ulcer areas and time to closure. Secondary amputation including major and minor amputations was used to assess the safety profile. RESULTS: Out of 715 studies, 32 were selected which enrolled 2880 diabetic patients. The pooled analysis revealed that NPWT including vacuum assisted closure (VAC) and vacuum sealing drainage (VSD) were as efficacious as ultrasound debridement improving healed ulcers, odds ratio, 0.86; 95% CI 0.28 to 2.6 and 1.2; 95% CI 0.38 to 4, respectively. However, both were better to standard wound care in wound healing patients. Compared with the standard wound care treated diabetic foot ulcers, NPWT and UD resulted in a significantly superior efficacy in time to wound closure and decrement in area of wound. No significances were observed between NPWT and UD groups in both indicators. Fewer patients tended to receive amputation in NPWT and UD groups compared to standard wound care group. CONCLUSIONS: The results of the network meta-analysis indicated that negative pressure wound therapy was similar to ultrasound debridement for diabetic foot ulcers, but better than standard wound care both in efficacy and safety profile. PMID- 26550166 TI - Lack of association between interleukin-2 (IL-2) gene rs2069762 polymorphism and cancer risk: a meta-analysis. AB - Interleukin-2 (IL-2) is an important member of the cytokines that play critical roles in carcinogenesis. Many studies have investigated the association between IL-2 rs2069762 polymorphism and cancer risk; however, the results remain controversial. The aim of this study is to assess the correlation between IL-2 rs2069762 polymorphism and cancer risk. All eligible case-control studies accorded with criteria published up to March 30, 2015 were identified by searching Embase and PubMed databases. Association between IL-2 rs2069762 polymorphism and cancer risk was assessed by crude odds ratios (ORs) with 95% confidence intervals (CIs), respectively. Ten case-control studies from nine publications with 3095 cases and 4480 controls were included. Overall, IL-2 rs2069762 polymorphism was not associated with cancer risk in five genetic models (G vs. T: OR = 1.07, 95% CI = 0.95-1.21, P = 0.278; GG vs. TT: OR = 1.16, 95% CI = 0.86-1.57, P = 0.317; GG + TG vs. TT: OR = 1.09, 95% CI = 0.93-1.28, P = 0.273; GG vs. TT + TG: OR = 1.11, 95% CI = 0.85-1.44, P = 0.451; TG vs. TT: OR = 1.08, 95% CI = 0.92-1.28, P = 0.339, respectively). Similar results were also obtained after stratified by ethnicity and cancer type. This meta-analysis indicates that IL-2 rs2069762 T>G polymorphism is not associated with cancer risk. And the same conclusion is drawn after stratified by cancer type and ethnicity. PMID- 26550167 TI - The association between DVWA polymorphisms and osteoarthritis susceptibility: a genetic meta-analysis. AB - It has been reported that the double von Willebrandfactor domain A (DVWA) gene polymorphisms may be associated with osteoarthritis (OA) risk. However, some studies yielded conflicting results. Therefore, we conducted a comprehensive meta analysis to identify the association of DVWA gene polymorphisms and the susceptibility to OA. We conducted a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet (CNKI) and Wangfang databases up to May 15, 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 11 studies from five articles with 13,579 subjectswere included in this meta-analysis. The overall results indicated that there was a significant association between DVWA rs7639618 polymorphism and OA susceptibility observed in dominant and co-dominant models. In the subgroup analysis, we found that DVWA gene rs7639618 and rs11718863 polymorphism was associated with OA risk in Asians (GG+GA vs. AA: OR=1.34, P<0.001; G vs. A: OR=1.29, P=0.019). Furthermore, for rs7639618, the dominant (GG+GA) and heterozygote (GA) may strongly increase the knee OA susceptibility (GG+GA vs. AA: OR=1.27, P<0.001), especially in Asians. In addition, as for rs11718863, a trend of increased knee OA risk was found in Asians (TT+TA vs. AA: OR=1.54, P<0.001). In conclusion, the meta-analysis results suggested that DVWArs7639618 and rs11718863 polymorphisms may increase the risk of knee OA susceptibility in Asians, but not in Caucasians. However, no significant association between SNP rs7639618 and rs11718863 and hip OA risk was identified. PMID- 26550169 TI - Captopril, an angiotensin-converting enzyme inhibitor, possesses chondroprotective efficacy in a rat model of osteoarthritis through suppression local renin-angiotensin system. AB - OBJECTIVE: A local tissue-specific renin-angiotensin system (local RAS) has emerged as a regulator of cartilage development and homeostasis. However, no report has described the chondroprotective efficacy of RAS inhibitor. Therefore, we studied the pharmacological function of captopril on hypertrophic differentiation of chondrocytes, cartilaginous degeneration and RAS components expression in a rat model of osteoarthritis (OA). METHODS: OA was surgically induced in the right knee of male rats. Animal groups included age matched sham control (sham group), OA placebo (OA group), and OA treated with captopril (CAP group). Eight weeks after the induction of OA, the tibias were isolated and the sagittal sections were stained with Safranin O and Masson-Trichrome. The mRNA and protein expression of RAS components were measured by qRT-PCR and western blotting respectively. RESULTS: The thickness of articular cartilage was reduced in the proximal tibia of the OA group, and decreased thickness of articular cartilage of the OA mice was effectively reversed by captopril treatment. Histological analyses revealed remarkable chondrocytes abnormality in OA rats, which were characterized by a marked expansion of hypertrophic zone and inhibition of proliferative zone of chondrocytes in the epiphyseal growth plate of tibia. However, captopril-treated could reverse chondrocytes abnormality in OA rats. Furthermore, the mRNA and protein expression of RAS components, renin, ACE, Ang II AT1R were upregulated in the proximal tibia of OA rats, however, the AT2R expression was suppressed. Intriguingly, captopril-treated could inhibit the activation of RAS in OA rats. CONCLUSIONS: The present study demonstrated that captopril could attenuate OA-induced osteoarticular injury, at least partially, through suppression local RAS. PMID- 26550168 TI - Protective effects of remote ischemic preconditioning in isolated rat hearts. AB - To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID- 26550170 TI - Use an alginate scaffold-bone marrow stromal cell (BMSC) complex for the treatment of acute liver failure in rats. AB - To evaluate the effects of alginate scaffold-bone marrow stromal cell (BMSC) in the treatment of acute liver failure in rats and provide a basis for in vivo application of artificial liver tissue. CM-DiI-labeled BMSCs were planted and grown on alginate scaffolds to form alginate scaffold-BMSC complex. Alginate scaffold-BMSC complex (the experimental group) or alginate scaffolds (the control group) were placed onto the surface of liver wound of rats after 70% of hepatectomy. The scaffold-BMSC complex and alginate scaffolds were removed after 4 weeks and fluorescence microscopy was used to track the growth and distribution of CM-DiI-labeled BMSCs. The liver tissues were stained for albumin and glycogen to investigate the differentiation of BMSCs on alginate scaffolds. The survival rate and liver function were also compared between the two groups of rats. BMSCs on alginate scaffolds and liver tissues were clearly demonstrated by CM-DiI labeling. BMSCs on alginate scaffolds secreted albumin and produced glycogen. The survival rate and liver function of the rats of the experimental group were significantly higher than that the control group rats. Alginate scaffold-BMSC complex promotes the regeneration of liver tissues in rats of acute liver failure. PMID- 26550171 TI - Interleukin-6 gene -174G/C polymorphism and bronchial asthma risk: a meta analysis. AB - The Interleukin-6 (IL-6) genetic polymorphism is associated with bronchial asthma, a number of studies have been conducted to investigate the association between IL-6 gene -174G/C polymorphism and bronchial asthma risk. However, the results are inconclusive. This meta-analysis aims to investigate whether -174G/C polymorphism is a potential risk factor for bronchial asthma. We searched Web of Science, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI) and Wanfang Database from inception through December 1st, 2014. Meta-analysis was performed using the STATA 12.0. Overall, a significantly reduced risk for asthma was found in IL-6 -174 CC genotype (CC vs. GG: OR = 0. 51, 95% CI = 0.27-0.96, P = 0.038). Furthermore, analysis by ethnicity indicated that there was a markedly reduced risk for asthma in IL-6 -174 CC genotype in Caucasian (CC vs. GG: OR = 0.51, 95% CI = 0.27-0.96, P = 0.038). Analysis by age indicated that there was a significantly reduced risk for asthma in IL-6 -174 CC genotype in adults (CC vs. GG: OR = 0.47, 95% CI = 0.23-0.97, P = 0.042). In conclusion, the current meta analysis indicates that IL-6 -174 CC genotype may be a protective factor against asthma in Caucasian and adults. PMID- 26550172 TI - Long non-coding RNA UCA1 contributes to the progression of prostate cancer and regulates proliferation through KLF4-KRT6/13 signaling pathway. AB - Long non-coding RNAs (lncRNAs) UCA1 have been shown to paly an important regulatory roles in cancer biology, and UCA1 dysfunction is related to TNM stage, metastasis and postoperative survival in several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of prostate cancer (PC) remain largely unclear. Herein, we found that UCA1 was abnormally upregulated in tumor tissues from PC patients, and patients with high UCA1 levels had a significantly poorer prognosis. Intriguingly, the mRNA and protein levels of KLF4 were significantly increased in tumor tissues, which was highly correlated to UCA1 levels. Moreover, UCA1 depletion inhibited the growth and induced apoptosis in PC3 and LNCaP cell lines. In addition, UCA1 loss-of-function could decrease KLF4 expression, subsequently, the downregulation of KRT6 and KRT13. Taken together, our study indicated that UCA1 had a crucial role in the tumorigenesis of PC. Moreover, UCA1 loss-of-function inhibited cell proliferation and induced cell apoptosis, at least partially, through inactivation KLF4-KRT6/13 cascade. PMID- 26550173 TI - Effects of cryptotanshinone on the expression levels of inflammatory factors in myocardial cells caused by Ang II and its mechanism. AB - OBJECTIVE: This study aims to explore the effects of the traditional Chinese medicine monomer cryptotanshinone (CTS) on the expression levels of inflammatory factors in myocardial cells caused by Ang II and its mechanism. METHODS: The neonatal rat myocardial cells were cultured in vitro in this study. Their purities were identified by immunocytochemical method. The cellular viability in different groups was determined by MTT assay. The levels of TNF-alpha and IL-6 in the supernatant of cell culture were detected with ELISA method. The levels of intracellular reactive oxygen species (ROS) were detected by Dihydrogen ethidium (DHE) staining method. The location changes of NF-kappaB in cells were detected by immunofluorescence method. RESULTS: The purity of primary cultured neonatal rat myocardial cells was over 95%, CTS had no obvious effect on the viability of cells while it inhibited the increased levels of TNF-alpha, IL-6 and ROS caused by Ang II with dose dependent. NF-kappaB mainly distributed in the cytoplasmic region in normal cells, it translocated to the nucleus after Ang II stimulation while CTS inhibited the translocation. CONCLUSIONS: CTS could inhibit the inflammatory factors such as TNF-alpha and IL-6 in myocardial cells induced by Ang II with dose dependent, its mechanism may be related with that CTS could decrease the levels of ROS in myocardial cells and inhibit NF-kappaB translocation into the nucleus. PMID- 26550174 TI - Correlation between single nucleotide polymorphism of FCRL-3 gene and Graves' disease in Han population of northern Anhui province, China. AB - OBJECTIVE: The frequency distribution of A/G genotype at position-169 in promoter of FCRL3 gene (Fc receptor-like 3) was identified in Han population of northern Anhui Province. The correlation between single nucleotide polymorphism (SNP) at this site and genetic susceptibility of Graves disease (GD) was discussed. How the genotype at this position correlated to age, gender, severity of goiter, presence or absence of exophthalmos, levels of thyrotrophin receptor antibody (TRab), thyroid peroxidase antibody (TpoAb) and anti-thyroglobulin antibody (TgAb) and thyroid function was analyzed in details. METHOD: Peripheral venous blood was collected for DNA extraction. SNP at position-169 in the promoter of FCRL3 gene was determined by using PCR-RELP among 180 GD cases and 146 normal subjects. Thyroid function tests and antibody detection were performed. RESULTS: The frequency of GG genotype of position-169 in promoter of FCRL3 gene was higher in GD group than in control group. The frequency was 28.9% and 13.8%, respectively, showing significant differences in intergroup comparison (chi(2)=6.618, P=0.046). The G allele frequency of GD group and control group was 49.4% and 40.4%, respectively, also showing significant differences between the groups (chi(2)=5.308, P=0.021). GD cases with AA, AG and GG genotypes at position 169 in FCRL3 promoter had significant differences in serum level of TRAb (chi(2)=7.319, P=0.026). However, no significant differences in gender, severity of goiter, TpoAb and TgAb level, presence or absence of exophthalmos and thyroid function (FT3, FT4, TSH) were found between the three genotypes (P>0.05). CONCLUSION: A/G SNP at position-169 in promoter of FCRL3 gene was correlated with susceptibility to GD among Han population in northern Anhui Province. G allele may contribute to the susceptibility to GD and correlate to positive TRAb result in thyroid diseases, but not to age of onset, gender, presence or absence of exophthalmos, thyroid function, TpoAb and TgAb level or severity of goiter. PMID- 26550175 TI - Percutaneous transapical access for pulmonary vein mapping and ablation in a porcine model with a new high-density electroanatomical mapping system. AB - INTRODUCTION: The porcine model is generally accepted for the development and testing of new forms oftherapy including ablation of atrial fibrillation (AF). However, the challenging left atrial (LA) and pulmonary vein (PV) anatomy enables only limited percutaneous catheter-based PV access. RESULTS: Here we present I) an alternative percutaneous transapical access, which enables easy and safe retrograde transmitral LA and PV mapping and ablation; II) early experience of LA mapping and successful circumferential PV isolation with novel mapping system (Rhythmia(TM)) and new generation of ablation catheter equipped with micro electrodes (IntellaTip MiFi). CONCLUSION: Although the experience with the transapical approach is limited, the initial results are promising as this may offer an alternative approach for tasting new technologies and translational research. PMID- 26550176 TI - Accuracy of bronchoalveolar lavage enzyme-linked immunospot assay to diagnose smear-negative tuberculosis: a meta-analysis. AB - PURPOSE: While the bronchoalveolar lavage enzyme-linked immunospot assay (BAL ELISPOT) shows promise for diagnosing smear-negative tuberculosis, its accuracy remains controversial. We meta-analyzed the available evidence to obtain a clearer understanding of the diagnostic accuracy. METHODS: Studies of the diagnostic performance of ELI-SPOT on smear-negative tuberculosis were identified through systematic searches of the PubMed and EMBASE databases. Pooled data on sensitivity, specificity and other measures of accuracy were meta-analyzed using a random-effects model. Summary receiver operating characteristic curves were used to assess overall test performance. RESULTS: A total of 7 studies were included in the meta-analysis. Diagnostic performance was as follows: sensitivity, 0.89 (95% CI 0.84 to 0.93); specificity, 0.78 (95% CI 0.74 to 0.81); positive likelihood ratio, 4.2 (95% CI 2.42 to 7.28); negative likelihood ratio, 0.14 (95% CI 0.06 to 0.33); diagnostic odds ratio, 36.16 (95% CI 9.70 to 134.73); and area under the curve, 0.9605 (SEM 0.0247). CONCLUSIONS: Available evidence suggests that BAL-ELISPOT may perform better than blood-ELISPOT for both screening and confirming a diagnosis of smear-negative tuberculosis. Nevertheless, BAL-ELISPOT should be not used alone but rather in parallel with clinical manifestations and conventional tests to ensure reliable diagnosis. PMID- 26550177 TI - Wnt/beta-catenin up-regulates Midkine expression in glioma cells. AB - Midkine, also known as neurite growth-promoting factor 2 (NEGF2), plays an important role in cell proliferation, apoptosis and differentiation. Recent studies have shown that Midkine is up-regulated in several types of human cancers. However, the molecular mechanism for its up-regulation remains poorly understood. Activation of Wnt/beta-catenin signaling is viewed as crucial for multiple tumor growth and metastasis, including glioma. In the present study, we found that Wnt3a administration or transfection of a constitutively activated beta-catenin promoted Midkine expression in glioma cells. We further identified a TCF/LEF binding site, with which beta-catenin interacts, on the proximal promoter region of Midkine gene, by luciferase reporter and chromatin immunoprecipitation assays. Thus, our results suggest a previously unknown Wnt/beta-catenin/Midkine molecular network controlling glioma development. PMID- 26550178 TI - Effect of hypoxia inducible factor-1 antisense oligonucleotide on liver cancer. AB - Hepatocellular carcinoma (HCC) is one of the most frequent primary malignancies of the liver and is resistant to anticancer drugs. Hypoxia is a master cause of tumor resistance to chemotherapy. Hypoxia-inducible factor-one alpha (HIF-1alpha) plays a key role in the adaptive responses to hypoxic environments. HIF-1alpha is constitutively up-regulated in several tumor types might thus be implicated in tumor therapy resistance. We hypothesized that disruption of HIF-1alpha pathway could reverse the hypoxia-induced resistance to chemotherapy. In this report, we prepared DOTAP (a liposome formulation of a mono-cationic lipid N-[1-(2,3 Dioleoyloxy)]- N,N,N-trimethylammonium propane methylsulfate in sterile water) cationic liposomes containing an antisense oligonucleotide (AsODN) against HIF 1alpha. Gene transfer of antisense HIF-1alpha was effective in suppressing tumor growth, angiogenesis, and cell proliferation, and inducing cell apoptosis. Our results suggested that antisense HIF-1alpha therapy could be a therapeutic strategy for treating HCC. PMID- 26550179 TI - Angiotensin receptor blockers (ARBs) reduce the risk of lung cancer: a systematic review and meta-analysis. AB - Angiotensin receptor blockers (ARBs) are the most commonly used blood pressure lowering drugs in the world. However, the preventive value of ARBs on lung cancer is still controversial. Therefore, it was necessary for us to perform a meta analysis to evaluate the value of ARBs on lung cancer risk. We searched the PubMed database as well as the Web of Science database. The overall effect was measured by odds ratio (OR) and corresponding 95% confidence intervals (CI). The significance of the pooled ORs was determined by the Z test with a P value less than 0.05 considering statistically significant. In this meta-analysis, we found ARBs could decrease the lung cancer risk (OR=0.81, 95% CI 0.69-0.54). The stability of the results was tested by sensitivity analysis. The result was not a significant change, suggesting that the result of our meta-analysis was stable. In conclusion, our meta-analysis demonstrated that ARBs was significantly associated with lower lung cancer. PMID- 26550180 TI - Peroxisome proliferator-activated receptor gamma (PPARG) rs1801282 C>G polymorphism is associated with cancer susceptibility in asians: an updated meta analysis. AB - Peroxisome proliferator-activated receptor gamma (PPARG) is related to inflammation and plays an important role in the development of cancer. PPARG rs1801282 C>G polymorphism might influence the risk of cancer by regulating production of PPARG gene. Hence, a comprehensive meta-analysis was conducted to explore the association of PPARG rs1801282 C>G polymorphism with cancer susceptibility. An extensive search of PubMed and Embase databases for all relevant publications was carried out. A total of 38 publications with 16,844 cancer cases and 23,736 controls for PPARG rs1801282 C>G polymorphism were recruited in our study. Our results indicated that PPARG rs1801282 C>G variants were associated with an increased cancer risk in Asian populations and gastric cancer. In summary, the findings suggest that PPARG rs1801282 C>G polymorphism may play a crucial role in malignant transformation and the development of cancer. PMID- 26550181 TI - RNA interference-mediated NOTCH3 knockdown induces phenotype switching of vascular smooth muscle cells in vitro. AB - Notch3 plays an important role in differentiation, migration and signal transduction of vascular smooth muscle cells (VSMCs). In this study, we used RNA interference (RNAi) technique to investigate the effect of knocking down the expression of the NOTCH3 gene in VSMCs on the phenotype determination under pathologic status. Real-time PCR and Western Blot experiments verified the expression levels of Notch3 mRNA and protein were reduced more than 40% and 50% in the NOTCH3 siRNA group. When the expression of Notch3 was decreased, the proliferation, apoptosis and immigration of VSMCs were enhanced compared to control groups (P < 0.01). NOTCH3 siRNA VSMCs observed using confocal microscopy showed abnormal nuclear configuration, a disorganized actin filament system, polygonal cell shapes, and decreasing cell sizes. Additionally, knocking down the expression of NOTCH3 may evoke the CASR and FAK expression. In Conclusion, interfering with the expression of NOTCH3 causes VSMCs to exhibit an intermediate phenotype. CaSR and FAK may be involved in the Notch3 signaling pathway. PMID- 26550182 TI - Lack of association between cyclin D1 A870G (rs9344) polymorphism and esophageal squamous cell carcinoma risk: case-control study and meta-analysis. AB - Studies examining the association between the cyclin D1 (CCND1) A870G (rs9344 G>A) polymorphism and esophageal squamous cell carcinoma (ESCC) have yielded inconsistent results. Here, we conducted a hospital-based case-control study in a Chinese Han population to assess the association between the CCND1 A870G polymorphism and ESCC. We then performed a meta-analysis to further investigate this association. We recruited 629 patients with ESCC and 686 cancer-free controls. Genotyping was performed with the polymerase chain reaction-ligase detection reactions (PCR-LDR) method. The meta-analysis was performed with the STATA 12.0 software. The case-control study showed no significant difference between the ESCC cases and controls in the allele frequencies or genotype distributions of the CCND1 A870G polymorphism. To obtain a more precise estimate of this relationship, we performed a meta-analysis of seven case-control studies involving a total of 2080 ESCC cases and 2833 controls. The meta-analysis suggested that the CCND1 A870G polymorphism is not associated with a risk of ESCC. A further subgroup analysis based on ethnicity also detected no association. This study suggests that the CCND1 A870G polymorphism is not associated with the risk of ESCC. PMID- 26550183 TI - Estrogen receptor alpha (ESR1) IVS1-397T>C polymorphism lowers risk of fracture. AB - BACKGROUND: Genetic factors are reported to affect fracture incidence. Many groups have explored the correlation of fracture risk with ESR1 IVS1-397T>C. The observed associations, however, are largely inconsistent. This meta-analysis of data from early-released studies was performed in an effort to determine the role of IVS1-397T>C in fracture. METHODS: Relevant studies were searched through Pubmed, Embase, ScienceDirect, and Wiley Online Library databases. 16 studies meeting all selection criteria were finally identified. We calculated ORs with 95% CIs to assess risk of fracture. Subgroup analyses were performed by subtype, ethnicity and gender. RESULTS: Data on 2916 cases and 19170 controls were analyzed in the meta-analysis. Overall, we found moderately decreased risk in association with IVS1-397 CC genotype (OR = 0.82, 95% CI = 0.73-0.92; OR = 0.84, 95% CI = 0.76-0.94). The decrease persisted in both hip fracture (OR = 0.82, 95% CI = 0.71-0.94; OR = 0.83, 95% CI = 0.73-0.94) and vertebral fracture (OR = 0.67, 95% CI = 0.50-0.91; OR = 0.78, 95% CI = 0.64-0.97; OR = 0.82, 95% CI = 0.68-0.98) when data were stratified by subtype. We also found a significant trend of decreasing risk in relation to the CC genotype in Caucasian, male and female. All fixed-effects meta-analysis results were homogeneous. CONCLUSION: The meta analysis demonstrates that risk of fracture seems likely to be decreased due to IVS1-397 CC or CT genotype. PMID- 26550184 TI - Effects of parasagittal meningiomas on intracranial venous circulation assessed by the virtual reality technology. AB - OBJECTIVE: This study is to investigate the compensatory intracranial venous pathways in parasagittal meningiomas (PSM) patients by virtual reality technology. METHODS: A total of 48 PSM patients (tumor group) and 20 patients with trigeminal neuralgia and hemifacial spasm but without intracranial venous diseases (control group) were enrolled. All patients underwent 3D CE-MRV examination. The 3D reconstructed images by virtual reality technology were used for assessment of diameter and number of intracranial veins, tumor location, venous sinus invasion degree and collateral circulation formation. RESULTS: Diameter of bridging veins in posterior 1/3 superior sagittal sinus (SSS) in tumor group was significantly smaller than that of the control group (P < 0.05). For tumors located in mid 1/3 SSS, diameter of bridging veins and vein of Labbe (VL) in posterior 1/3 SSS decreased significantly (P < 0.05). For tumors located in posterior 1/3 SSS, bridging vein number and transverse sinus (TS) diameter significantly decreased while superficial Sylvian vein (SSV) diameter increased significantly (P < 0.05). Compared with tumor in posterior 1/3 SSS subgroup, number of bridging veins in the tumor in mid 1/3 SSS subgroup increased significantly (P < 0.05). Compared with control group, only the bridging vein number in anterior 1/3 SSS segment in invasion Type 3-4 tumor subgroup decreased significantly (P < 0.05). Diameter of TS and bridging veins in posterior 1/3 SSS segment in sinus invasion Type 5-6 tumor subgroup decreased significantly (P < 0.05). Compared with control group, only the diameter of VL and TS of collateral circulation Grade 1 tumor subgroup decreased significantly (P < 0.05) while in Grade 3 tumor subgroup, TS diameter decreased and SSV diameter increased significantly (P < 0.05). CONCLUSIONS: The intracranial blood flow is mainly drained through SSV drainage after SSS occlusion by PSM. PMID- 26550185 TI - Xiangqing anodyne spray (XQAS): a combination of ethanol extracts of Cynanchum paniculatum and Illicium henryi for treating soft-tissue injury. AB - PURPOSE: To compare the pharmacodynamic effects of an anodyne spray (XQAS) containing extracts of two herbs, Cynanchum paniculatum (CP) and Illicium henryi (IH), with those of spray containing the vehicle alone, CP alone (CPS) or IH alone (IHS), when applied topically acute soft tissue injury (STI) in an animal model. METHODS: Acute closed STI was modeled by hammer blow in the hind leg muscle of rat. In the acute test, XQAS, vehicle and normal saline (NS) were applied topically with instantly and repeatedly every 2 h for 8 h after modeling. In the chronic test, XQAS, vehicle, NS, CPS and IHS were applied topically respectively with instantly and repeatedly every 8 h for 96 h after modeling. RESULTS: XQAS (150 MUl/time) rapidly suppressed STI-caused muscle swelling, high contents of inflammatory mediators such as prostaglandin-E2, interleukin-lbeta, nitric oxide and so on. XQAS (100 and 250 MUl/time) also showed chronic effects with dose-dependent suppressions of muscle swelling, up-regulated mRNA expressions of nuclear factor-kappaB p65 (NF-kappaB p65), cyclooxygenase-2 and interleukin-lbeta, high contents of inflammatory mediators, and muscle cells impairment and necrosis induced by STI, while XQAS was more effective than CPS or HIS on treating STI. CONCLUSION: XQAS can suppress STI-caused increased gene expressions of NF-kappaB p65 and its downstream genes which mediate biosyntheses of inflammatory mediators, resulting in suppressed swelling, inflammatory reaction and cell impairment in the injured muscle. There is a synergistic effect between CPS and IHS on curing STI. PMID- 26550186 TI - Prognostic significance of placenta growth factor expression in patients with multiple cancers: a meta-analysis. AB - BACKGROUND: Placenta growth factor (PLGF) is a member of the vascular endothelial growth factor (VEGF) family which is associated with the progression and metastasis of cancer. However, whether it can be used to predict prognosis in multiple cancer is still inconsistent. METHODS: A meta-analysis was performed by searching electronic databases updated to December 2014. Eligible studies which evaluated the relationship between PLGF expression level and survival of patients with multiple cancers were conducted. Overall survival (OS), progression-free survival (PFS), hazard ratio (HR), and 95% confidence intervals (CI) were calculated. RESULTS: Nineteen studies with a variety of cancers were included for the meta-analysis. Combined HR suggested that high expression of PLGF significantly associated with a poor OS (HR=1.69, 95% CI, 1.32-2.16), and PFS (HR=1.8, 95% CI, 1.33-2.44) in patients with different cancers. Moreover, a subgroup analysis based on cancer type demonstrated that high expression level of PLGF predict poor OS in both digestive system carcinoma (HR=1.63, 95% CI, 1.21 2.19; I(2)=80.7%, P<0.001) and respiratory system tumor (HR=1.75, 95% CI, 1.28 2.41; I(2)=0.0%, P=0.394). For PFS, the similar result was found in respiratory system tumor (HR=1.64, 95% CI, 1.23-2.19; I(2)=0.0%, P=0.807), but not in digestive system carcinoma (HR=1.81, 95% CI, 0.93-3.52; I(2)=80.2%, P<0.001). CONCLUSION: Our meta-analysis demonstrates that PLGF might be regarded as a poor prognostic fact for multiple cancers. More large-scale and well-designed studies are still needed to strengthen our findings. PMID- 26550187 TI - Involvement of AQP 1 in the cardio-protective effect of remifentanil post conditioning in ischemia/reperfusion rats. AB - BACKGROUND: our research aim to study the role of AQP1 in the cardioprotective effect of remifentanil post-conditioning for myocardial ischemia/reperfusion injury. METHODS: Ninety Sprague-Dawley (SD) rats were divided into 6 groups: sham operation group (Sham group), myocardial ischemia and reperfusion group (I/R group), postconditioning of remifentanil group (R-post), postconditioning of remifentanil plus AQP1 inhibitor acetazolamide group (R-post +Ace), postconditioning of remifentanil plus opioid-receptor antagonist compounds (R post +AC), postconditioning of remifentanil plus AQP1 enhancer arginine vasopressin (R-post +AV). All groups except the sham operation group were given 30 min ischemia in left anterior descending (LAD) coronary arteries. All groups were then given 120 min reperfusion to the LAD. Before reperfusion, the R-post, R post +Ace, R-post +AC, R-post +AV groups were given 10 min remifentanil post conditioning. Hemodynamic data were measured every 30 min after initiation of ischemia. The rats' hearts were exercised for detecting infarct size and water content in the left ventricle, and AQP1 expression were also detected. RESULTS: The R-post group showed a significant reduction of the infarct size compared to the I/R group. The effect of R-post for reducing infarct size was slightly enhanced by adding acetazolamide to R-post, so significant differences could still be found when compared R-post+Ace group to the I/R group. The effect of infarct size reduction brought by R-post was blocked by the opioid-receptor antagonist compounds. This effect was also blocked by the AQP1 enhancer. Similar outcomes were found considering the water content of the left ventricle and the AQP1 expression. CONCLUSION: Cardioprotective effect of remifentanil post conditioning may initiate through inhibiting the function of AQP1. PMID- 26550188 TI - Correlation of secreted protein acidic and rich in cysteine with diabetic nephropathy. AB - To detect the serum concentrations of secreted protein acidic and rich in cysteine (SPARC) in patients with diabetic nephropathy and SPARC mRNA and protein expressions in renal tissue of db/db mice (C57BL/KsJ, diabetic nephropathy mice), thus preliminary exploration on the role of secreted protein acidic riches in cysteine in the development of diabetic nephropathy were carried out. Serum SPARC levels in normal subjects, patients with type 2 diabetes mellitus (without diabetic nephropathy), chronic renal failure (without diabetes mellitus), and diabetic nephropathy were determined with enzyme-linked immunosorbent assay. 12 week-old db/db mice (db/db group) and its littermate wild-type control mice (NC group) were selected with 6 from each group, and the kidney tissue were taken. RT PCR, Western blot, and immunofluorescence were used to detect the mRNA, targeted protein expressions of SPARC and the staining of renal tissue. The serum level of SPARC in diabetic nephropathy group was significantly higher than those in normal group, type 2 diabetes mellitus, and chronic renal failure group (P < 0.05 or P < 0.01). The SPARC level in the type 2 diabetes mellitus group was higher than that in normal group (P < 0.05), but there was no difference between normal group and chronic renal failure. SPARC mRNA and protein levels in renal tissue of db/db mice were higher compared with the normal control group (P < 0.05). The long term hyperglycemic state in patients with diabetic nephropathy causes pathological change of renal tissue. Simultaneously, increased secretion of SPARC from renal tissue results in elevation of serum SPARC level. SPARC correlates with the occurrence and progression of diabetes, and it may play a role in pathological change of diabetic nephropathy. PMID- 26550189 TI - Anxiolytic effect of essential oils of Salvia miltiorrhiza in rats. AB - This study aims to investigate the anxiolytic effects of essential oil from S. miltiorrhiza in rats. The elevated plus maze test and the social interaction test were performed to evaluate the anxiolytic effects of essential oil. The levels of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) in cerebral cortex of rats as well as the plasma corticosterone (CORT) level were examined in the rats with the treatment of essential oil. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders. The catalepsy test was carried out to investigate whether essential oil induces the catalepsy. Our results showed that oral administration of essential oil increased the percentage of time spent in the open arms and increased the number of entries to the open arms in the elevated plus maze test. Oral administration of essential oil also increased the time for social interaction in rats. No apparent extrapyramidal symptom (EPS) was observed in the animals with essential oil treatment. The effect of essential oil in the intracellular chloride (Cl(-)) concentration in the cultured human neuroblastoma cells was assessed. Treatment with essential oil (50-100 mg/kg) increased intracellular Cl(-) concentration in the cell culture in a dose-dependent manner, suggesting the involvement of GABAA receptor-Cl(-) ion channel. Together, our data indicate an anxiolytic effect induced by the essential oil from S. miltiorrhiza. PMID- 26550190 TI - Prognostic significance of osteopontin in patients with non-small cell lung cancer: results from a meta-analysis. AB - BACKGROUNDS: Non-small cell lung cancer (NSCLC) is one of the most common malignancies with a high mortality level. Recently, a variety of studies explored the role of osteopontin (OPN) expression in the prognosis of NSCLC, but the results were controversial. METHODS: We performed a meta-analysis of eligible studies to evaluate the prognostic significance of OPN expression in NSCLC patients. In order to assess the association between OPN and OS and DFS/PFS, hazard ratio (HR) with 95% confidence interval (CI) was calculated. RESULTS: A total of ten studies comprising 1420 patients were included in the meta-analysis. The summary results indicated that high OPN expression was a poor predictor for OS (HR = 2.19, 95% CI: 1.6-2.98), and DFS/PFS (HR = 2, 95% CI: 1.66-2.41). Subgroup analysis revealed that high OPN expression was a negative prognostic marker for OS and DFS/PFS regardless of ethnicity background, treatment and OPN detection method. CONCLUSION: Our results showed that increased OPN expression significantly correlated with poor OS and DPS/PFS in NSCLC patients. PMID- 26550191 TI - Bone mesenchymal stem cells overexpressing FGF4 contribute to liver regeneration in an animal model of liver cirrhosis. AB - It is recognized that Fibroblast Growth Factor 4 (FGF-4) could not only increase the proliferation of bone marrow mesenchymal stem cells (BMSCs), but also induce BMSCs into hepatocyte-like cells in vitro. However, the role of FGF4 played in liver regeneration in vivo is unclear. This study constructed FGF4 overexpressing BMSCs and then transplanted them into cirrhotic rats to investigate the role of FGF4 played in liver regeneration. The results showed that FGF4 promoted the location of the BMSCs only at the early stage, and more proliferating cell nuclear antigen (PCNA), epithelial cell adhesion molecule (EpCAM) and Jagged-1 positive hepatocytes were found in the cirrhotic rats. This study indicated that FGF4 transduced BMSCs contributed to liver regeneration might by the transplanted microenvironment. PMID- 26550192 TI - The effect of ozone on blood pressure in DOCA-salt-induced hypertensive rats. AB - BACKGROUND: Hypertension is a risk factor for the cardiovascular diseases. Ozone as a therapeutic agent for the treatment of several disorders. We aimed to observe the effects of ozone on the blood pressure in DOCA-salt hypertensive rats. METHODS: Twenty three young Sprague Dawley male rats were divided into three groups; Control (C), Hypertension (H) and Hypertension + Ozone (HO). Hypertension was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly, 4 weeks, whereas intraperitoneal ozone was administered (1.1 mg/kg) for 10 days. Serum endothelin-1, nitric oxide and renin levels were measured with ELISA. Blood pressures were monitored using a tail cuff system. Endothelin-1, ET receptor A and ET receptor B mRNA expression in heart and vascular tissue were assessed by quantitative reverse transcription polymerase chain reaction. RESULTS: Blood pressure, serum endothelin-1 and ET receptor A mRNA expression levels were increased in H group, whereas serum renin, nitric oxide and ET receptor B mRNA expression levels in the heart and vascular tissue decreased compared with C and HO groups, which were counteracted by ozone treatment. CONCLUSION: Ozone treatment decreases blood pressure and is effective in preventing the progression of hypertensive disease, the mechanisms of which are associated with anti vasoconstrictor effects through reducing the levels of serum endothelin-1 and ET receptor A mRNA expression in the heart and vascular tissue. PMID- 26550193 TI - Role of WISP3 siRNA in proliferation, apoptosis and invasion of bladder cancer cells. AB - Bladder cancer (BC) is the most common cancers of the urinary tract worldwide, killing thousands of people a year. WISP3 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of proteins. Increasing evidences have linked abnormal levels of CCN family members to tumorigenic effects. In the present study, we found that WISP3 was overexpressed in BC. Knockdown of WISP3by RNA interference in two BC cell lines (5367 and SCaBER cells) significantly inhibited cell proliferation, which may be mediated by cell cycle arrest in G1 phase. Moreover, silencing of WISP3 also induced cell apoptosis via increasing the expression of caspase 3 and caspase 9. Depletion of WISP3 notably inhibited the invasion of BC cells. Our data suggests that inhibition of WISP3 may be a therapeutic strategy for BC. PMID- 26550194 TI - Survival implications of pretreatment pelvic CT in rectal cancer patients after neoadjuvant chemoradiotherapy and surgery. AB - PURPOSE: To determine the correlation between pretreatment computed tomography (CT) data and survival duration after neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. MATERIALS AND METHODS: 122 consecutive patients with advanced rectal cancer were assessed retrospectively. Pretreatment imaging and postoperative data were evaluated through Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: Pretreatment CT identified 557 metastatic lymph nodes (mean, 4.55 per patient; median 4). Survival durations were measured during the period between the application of CT and death or the last follow-up examination. Univariate analysis showed that the following factors had a significant impact on survival: maximum tumor diameter (P = 0.019), distance from inferior tumor margin to anorectal ring (P <0.0001), number of lymph nodes involved in patients with short-axis, lymph node diameter >=8 mm (P <0.0001) in pretreatment CT, distance from the anorectal ring (P = 0.027), ypN stage (P = 0.0008), ypM stage (P = 0.046) and number of metastatic lymph nodes (P <0.0001) in clinical assessment. Multivariate analysis showed that the following factors were significant: number of lymph nodes in patients with short-axis lymph node diameter >=5 mm but <8 mm (P = 0.044) and in those with this diameter >=8 mm (P = 0.028; pretreatment CT) and number of metastatic lymph nodes (assessed in histopathological examination). CONCLUSION: Pretreatment lymph node size and number can predict survival duration after treatment for locally advanced rectal cancer. For patients with lymph nodes >8 mm (short-axis diameter) and/or >1, such lymph nodes tend to have a poor performance for prognosis. PMID- 26550195 TI - Impact of MDM2 309T>G polymorphism on sarcomagenesis. AB - BACKGROUND: A series of epidemiological studies have attempted to evaluate the impact of 309T>G polymorphism in MDM2 gene frequently identified as a susceptibility loci for various cancers on malignant sarcomas, however the reported conclusions remain inconsistent and elusive. We pooled all usable data sets in order to systematically assess the association between 309T>G polymorphism and sarcoma risk. METHODS: To identify as many informative studies with complete data as possible, we searched a number of databases (PubMed, EBSCO, BIOSIS, the Cochrane Library, ISI Web of Science, Wiley Online Library and Embase). Inclusion criteria were defined to select the eligible studies. The fixed effects meta-analysis was properly used to calculate the pooled ORs and 95% CIs. MAJOR FINDINGS: We eventually identified six studies evaluating the association of sarcoma risk with 309T>G polymorphism. People with 309-GG were found to have 43% greater risk of sarcoma relative to people with 309-TT (OR, 1.43; 95% CI, 1.01~2.03; Pheterogeneity, 0.45). In the G vs. T genetic model, the risk reduced to 19% (OR, 1.19; 95% CI, 1.01~1.40; Pheterogeneity, 0.50). Statistical data showed no significant heterogeneity or publication bias in the meta-analysis. CONCLUSION: These data demonstrate that 309T>G polymorphism located within the MDM2 gene may act as modifier factor for sarcomas. A weakness of this analysis is that the findings cannot be explainable when the subtypes are separated and additional larger investigations are needed to identify the role of 309T>G polymorphism in each form of sarcoma. PMID- 26550196 TI - Bioinformatics analysis of the squalene synthase gene and the amino acid sequence in ginseng species. AB - The cDNA sequence, their structure, physical properties, signal peptide, hydrophobicity, hydrophilicity, subcellular localization domain of transmembrane domain and evolutionary relationship of encoded amino acid sequences were analyzed in squalene synthase of 9 species of ginseng plant using bioinformatics methods on GenBank. The results showed that the averaged similarity of squalene synthase cDNA sequence structure in Ginseng species was 96.245%, the similarity of the amino acid encoding sequence was 95.5%. The secondary structure prediction results showed that the amino acid sequence of 9 squalene synthase had alpha helix and random coil as the main components. After the phylogenetic analysis in 9 kinds of ginseng species, we found that they can be divided into two subfamilies. The analysis showed that plants, animals, yeasts belonged to different species, the homology was high within plant species and animal species. By analyzing the ginseng species squalene synthase and their encoding gene bioinformatics features, we can provide the theoretical reference for the squalene synthase gene cloning and the genetic manipulation. PMID- 26550197 TI - Lipoxin A4 ameliorates ischemia/reperfusion induced spinal cord injury in rabbit model. AB - Ischemia/reperfusion (I/R) induced spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repairaortic aneurysms. This study aims to investigate the neuroprotective effects of Lipoxin A4 and its potential mechanism in a rabbit model with I/R spinal cord injury. Forty-five rabbits were randomly divided into three groups: sham group, I/R group and Lipoxin A4 group. Rabbits were subject to 30 min aortic occlusion to induce transient spinal cord ischemia. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, as well as local malondialdehyde (MDA) and total superoxide dismutase (SOD) activity analysis. All animals in the I/R group became paraplegic. While after 48 hour treatment, compared with I/R group, Lipoxin A4 significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). These results suggest that Lipoxin A4 can ameliorate I/R induced spinal cord injury in Rabbit through its antiapoptosis and antioxidant activity. PMID- 26550198 TI - A novel method to derive and expand mice neural stem cells efficiently without neuro-sphere formation. AB - Neural stem cells (NSCs) are multi-potent stem cells able to self-renew and generate immature and differentiated cell populations by asymmetric division. The NSCs are of considerable interest for cell replacement in neuro-degenerative diseases. NSCs are usually identified and expanded by their ability to generate free-floating aggregates termed neurospheres. However, neurospheres are not a pure population of NSCs with as little as 1% population in primary spheres. Neurospheres also contain neurons, astrocytes and oligodendrocytes. The heterogeneity of these cells may hinder their repopulation potential when used in cell transplantation. Furthermore, to obtain 1 million NSCs by the neurosphere protocol usually takes one month, which is inconvenient for future clinical trials. In this study, we tried to derive the NSCs from mice embryo neuroepithelium without neurosphere formation. Three different protocols were compared. We generated a direct and efficient NSCs generation, expanding and freezing protocol. This protocol can provide sufficient amount of the NSCs from first a few passages for cell transplantation. PMID- 26550199 TI - MRI research of diaphragma sellae in patients with pituitary adenoma. AB - This study is to investigate the clinical significance of diaphragma sellae in patients with pituitary adenoma by MR images. A total of 47 cases of pituitary adenoma patients were enrolled in this study. Preoperative and postoperative MR scanning together with preoperative 3D-GE sequential scanning were performed. A series of parameters of diaphragma sellae were measured and compared. Tumor height was greater in patients with convex diaphragma sellae than that in patients with concave diaphragma sellae. The width and height of diaphragmal opening were positively related to tumor height. Diaphragmal opening width in the invasive group was greater than that of the non invasive group. Diaphragmal opening width in the non total resection group was significantly greater than that in the total resection group. Tumor resection rate was negatively correlated to diaphragmal opening width in the non total resection group. Lift angle of bilateral epidural around diaphragmal opening was positively related to tumor height. Enhanced 3D-GE images can perfectly display diaphragma sellae and parameters of tumor height and tumor invasiveness are related to diaphragmal opening diameter. PMID- 26550200 TI - Serum thymidine kinase 1 levels correlate with clinical characteristics of esophageal squamous cell carcinoma. AB - Patients with esophageal cancer are often diagnosed at advanced stages, leading to poor prognosis. Biomarkers are needed to enable earlier detection as well as to aid in the prediction of prognosis, but to date these tools remain scarce. Thymidine kinase (TK1) has been shown to exhibit altered expression levels in esophageal tumor cells, therefore this study sought to determine whether serum TK1 levels are also altered and, if so, to assess the utility of TK1 as a biomarker in esophageal squamous cell carcinoma. Eighty patients with esophageal squamous cell carcinoma were included as the case group and 80 healthy persons were selected as the control group. Serum TK1 levels, postoperatively for cancer patients, were detected by chemiluminescence. Follow-up was performed for cancer patients to determine the progression free survival (PFS) and overall survival (OS). Serum TK1 levels were significantly higher in cases of esophageal cancer than in healthy control individuals (t=7.235, P<0.05). When cancer cases were sub divided into lower and higher serum TK1 levels, based on the mean level of 3.38 pmol/L, statistically significant differences in TNM stage, tumor differentiation, and lymph node metastasis were observed between patients with >=3.38 pmol/L and <3.38 pmol/L (chi(2)=28.134, 3.187, 7.234, P<0.05). The average OS of all esophageal cancer patients was 30.13 months, and the average PFS was 24.73 months. However, when the cases were divided by serum TK1 level, average OS of those with higher serum TK1 (>=3.38 pmol/L) was significantly lower (23.98 mo) than those with lower serum TK1 (32.96 mo) (chi(2)=5.439, P<0.05). Similarly, average PFS was significantly lower in patients with higher serum TK1 (17.65 mo versus 27.62) (chi(2)=4.640, P<0.05). OS was correlated with TNM stage (hazard ratio, HR=3.116), degree of tumor differentiation (HR=0.427), lymph node metastasis (HR=0.535), and serum TK1 level (HR=1.913) (Wald chi(2)=6.782, 6.228, 4.562, 5.681, P<0.05). Similarly, PFS was correlated with TMN stage (HR=2.153), degree of tumor differentiation (HR=0.627), and serum TK1 level (HR=1.632) (Wald chi(2)=7.035, 5.335, 4.887, P<0.05). Thus, patients with esophageal squamous cell carcinoma exhibit higher circulating TK1 levels, consistent with findings of increased TK1 expression in tumor cells. Further, the correlation of serum TK1 levels with clinical features of esophageal cancer and with patient survival suggest that serum TK1 may serve as a valuable biomarker for predicting patient prognosis. PMID- 26550201 TI - Effects of calcium-sensing receptors on apoptosis in rat hippocampus during hypoxia/re-oxygenation through the ERK1/2 pathway. AB - OBJECTIVES: To explore the effects of calcium-sensing receptors (CaSR) on apoptosis in rat hippocampus during hypoxia/re-oxygenation (H/R). METHODS: After post-culturing of isolated rat hippocampus, the cultures were subjected to H/R, meanwhile gadolinium chloride (GdCl3, agonist of CaSR) and NPS 2390 (antagonists of CaSR) was added to reperfusion solution. The number of hippocampal neuron, cell proliferation assay and apoptosis rate was determined by inverted microscope, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometer (FCM). Besides, caspase-3, Bax, cytochrome C (Cyt-c), extracellular signal-regulated protein kinase (ERK) 1/2, pERK1/2, P38 and pP38 were analyzed by western blotting. RESULTS: The hippocampal neuron number and cell viability were significantly decreased after H/R treatment, and were further significantly reduced when co-treatment with CaSR agonist GdCl3. But the effects of GdCl3 were attenuated by NPS-2390. Whereas, apoptosis rate, the expression level of caspase-3, Bax and Cyt-c were all significantly increased under H/R condition, and was further significantly increased by GdCl3, but were reversed by NPS-2390 (P < 0.05). Moreover, there were no significant differences in expression of ERK1/2, P38 and pP38 among different groups. However, the expression of pERK1/2 was significantly increased after H/R treatment, but was significantly reduced by NPS 2390 (P < 0.05). CONCLUSION: The results suggest that CaSR might play significant roles in the induction of hippocampus apoptosis in rat during H/R through phosphorylation of ERK1/2. PMID- 26550202 TI - Presurgical orthodontic decompensation alters alveolar bone condition around mandibular incisors in adults with skeletal Class III malocclusion. AB - This study is to use cone beam computed tomography (CBCT) to acquire accurate radiographic images for alveolar bone in lower incisors and the change after presurgical orthodontic treatment. Seventeen patients with skeletal Class III malocclusion, ten normal occlusion subjects, and fifteen patients treated with orthodontic treatment and orthognathic surgery were included. CBCT images were obtained. The labial and lingual inclinations of mandibular incisors, the thickness of alveolar bone, the vertical alveolar height and root length were measured. Alveolar bone thickness at the apex in patients with skeletal Class III malocclusion was thinner than normal subjects. The vertical alveolar bone heights at labial and lingual sides in patients with skeletal Class III malocclusion were both reduced compared with normal subjects, especially at the labial side. There were statistically significant correlations between lower incisor inclination and alveolar bone morphology. After orthodontics, the incisors root apex was closer to the lingual side of alveolar bone. The alveolar bone thickness at apex was not statistically changed. The vertical alveolar bone heights at the labial and lingual sides were both significantly reduced especially the lingual side after presurgical orthodontic treatment. The root length was not significantly changed. In conclusion, the alveolar bone thickness at apex is thinner and the vertical alveolar height is reduced at the labial side. Forward movement of lower incisors during presurgical orthodontic treatment can render the lower incisors root apex closer to the lingual side and the vertical alveolar height is reduced. PMID- 26550203 TI - A simple and stable galactosemic cataract model for rats. AB - Rat galactosemic cataract is commonly used in the investigation of sugar cataract. In current study, 21-day sprague-dawley (SD) rats were randomly divided into two groups (n=42), which were fed by normal water and galactose solution (12.5%-10%) for 18 days respectively. Every 3 days, lens opacity was observed by a slit lamp, and 6 rats of each group were executed for the analysis of aldose reductase (AR) activity, galactitol level and AR mRNA expression. Morphological results showed that small vacuoles initially appeared in the equatorial area before the 6th day, then subsequently extended to the whole anterior capsule, and eventually developed to mature cataract on the 18th day. AR of galactosemic lenses was significantly activated in the first stage and then slowly dropped to the end accompanied by the related changes of galactitol. AR mRNA expression also was upregulated and reached the peak at the 6th day. This study appears to confirm that galactosemic cataract can be induced for 21-day SD rats by only drinking 12.5% to 10% galactose solution, and this model is simple, economical and stable as to meet the research needs. PMID- 26550204 TI - Accuracy of contrast-enhanced ultrasound in the identification of thyroid nodules: a meta-analysis. AB - This meta-analysis aimed to identify the accuracy of contrast-enhanced ultrasonography (CEUS) on the diagnosis of thyroid nodules. PubMed, Chinese Biomedical Medical databases (CNKI), Wan Fang (Chinese), and EBSCO database were searched from inception through April 15, 2015 without language and geographic restrictions. MetaDisc version 1.4 software was applied for this meta-analysis. We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratio (LR+/LR-), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Twenty-five eligible studies were included in this meta-analysis. A total of 424 in 1154 nodules is malignant thyroid tumors. After all thyroid lesions were histologically confirmed by CEUS, the pooled Sen was 0.88 (95% confidence interval [CI] 0.85-0.91); the pooled Spe was 0.90 (95% CI 0.88-0.92). The pooled positive LR+ was 8.69(95% CI 5.78-13.09); the pooled negative LR- was 0.15 (95% CI 0.12-0.19). The pooled DOR of CEUS in the diagnosis of thyroid nodules was 63.18 (95% CI 37.82-105.53). The area under the SROC curve was 0.946 (standard error [SE] = 0.010). Our meta-analysis indicates that CEUS may have high accuracy in diagnosis the difference between benign and malignant thyroid nodules. US is a traditional tool in the diagnosis thyroid nodules. However, with the development of science and technology, the emerging of CEUS significantly improve accuracy in the diagnosis thyroid nodules. PMID- 26550205 TI - A canine model of osteonecrosis of the femoral head induced by MRI guided argon helium cryotherapy system. AB - OBJECTIVE: This study is to identify the reliability of osteonecrosis of the femoral head (ONFH) modeling established by MRI guided argon helium cryotherapy system in beagles. METHODS: A total of 15 beagles were used to establish the ONFH model. The left femoral heads of the beagles received two cycles of argon helium freezing-thawing under MRI guidance and were considered as experimental group while the right femoral heads received only one cycle of argon helium freezing thawing and were considered as the control group. X-ray, MRI, general shape and histological examinations were performed so as to identify the effect of modeling. RESULTS: At 4 week after modeling, MRI showed obvious bilateral hip joint effusion and marked femoral head bone marrow high signal. At 8 week after surgery, abnormal signal appeared in bilateral femoral heads. T1WI showed irregular patchy low signal, T2WI showed irregular mixed signals and the joint capsule effusion showed long T1 and T2 changes. Twelve weeks after operation, T1WI showed a low signal strip with clear boundary and T2WI showed intermediate signal. The changes of the left femoral heads were significant while compared with those of the right sides. The lacunae rates of femoral heads in the experimental group at 4, 8, and 12 week after surgery (40.75 +/- 3.77, 57.46 +/- 4.01, 50.27 +/- 2.98) were higher than those in control group (30.08 +/- 3.61, 49.43 +/- 2.82, 40.56 +/- 2.73). CONCLUSION: Canine model of ONFH was successfully established using an argon helium cryotherapy system. PMID- 26550206 TI - Relationship between pituitary adenoma texture and collagen content revealed by comparative study of MRI and pathology analysis. AB - This study is to reveal the relationship between pituitary adenomas and tumor texture by comparing MRI and pathologic results. Preoperative imaging data of 38 cases of pituitary adenoma patients and collagen content of tumor specimens measured by histopathological were analyzed and compared. T2WI and diffusion coefficient assessment were used to reveal the relationship between tumor texture and collagen content. There were 13 cases of soft texture, 17 cases of medium texture and 8 cases of tough texture tumors. Signal intensity of different texture Pituitary adenomas had significant difference on T2WI and ADC map (P < 0.05). The signal intensity ratio of tumor and pons on T2WI had high consistency with tumor texture. Mean collagen contents of soft, medium and tough texture group were 1.51% +/- 0.91%, 7.35% +/- 2.99% and 18.10% +/- 8.24%, respectively. There were significant differences in collagen content of different texture tumors (P < 0.01). The signal intensity of T2WI and ADC images have prediction value for pituitary adenomas texture and T2WI is more reliable. PMID- 26550207 TI - RhoA activity increased in myocardium of arrhythmogenic cardiomyopathy patients and affected connexin 43 protein expression in HL-1 cells. AB - Arrhythmogenic cardiomyopathy (AC) is a familial heart muscle disease with mutations of desmosomal gene and its pathogenesis is related with mutations of desmosomal gene and abnormality of connexin43 (Cx43). One of Rho GTPase, RhoA involves in many pathological processes and is regulated by desmosomal gene PKP2. We aim to identify if PKP2 regulate RhoA activity in myocardium of AC patients, the activity change of RhoA in patients' myocardium and to investigate the effect of active RhoA on the protein expression of Cx43 in myocardial cells. The protein expression level was assessed by western blot and the activity of RhoA was assessed by RhoA protein activation assay. Our results showed that the expression of PKP2 was decreased in myocardium of three patients, one of which carried PKP2 mutations. The activity of RhoA in myocardium was increased in myocardium of AC as compared with healthy control except for the patient with PKP2 mutation, the expression of Cx43 was also increased in those patients with increased activity of RhoA. The results in vitro demonstrated that the increase of active RhoA can cause the change of protein expression of Cx43 in HL-1 cardiomyocytes. In conclusion, regulation of RhoA activity is complex in the myocardium of AC and the activity of RhoA is increased in AC patients without PKP2 mutations. What's more, the active RhoA affects the protein expression of Cx43 in vivo and in vitro, this may be the possible disease mechanism of AC. PMID- 26550208 TI - Angiotensinogen polymorphism and ischemic stroke risk. AB - The angiotensinogen M235T polymorphism was associated with ischemic stroke risk. However, the results were controversial. Thus, a meta-analysis was conducted. NCBI, Medline, Web of Science and Embase databases were systematically searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. There was a significant association between angiotensinogen M235T polymorphism and ischemic stroke risk (OR = 1.69; 95% CI, 1.35-2.11; P < 0.001). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with ischemic stroke in Asian (OR = 1.85; 95% CI, 1.45-2.35; P < 0.001). In the age subgroup, we found that angiotensinogen M235T polymorphism could increase both early-onset ischemic stroke risk (OR = 1.88; 95% CI, 1.33-2.43; P < 0.001) and late-onset ischemic stroke risk (OR = 1.20; 95% CI, 1.01-1.39; P = 0.04). This meta-analysis suggested that angiotensinogen M235T polymorphism was associated with ischemic stroke. PMID- 26550209 TI - Prognostic role of microRNA-25 in cancers: evidence from a meta-analysis. AB - BACKGROUND: miRNAs have been participated in human carcinogenesis as tumor oncogenes or suppressors, and have a prognostic significant for patients with cancers. In recent years, miR-25 was found associated with clinical value of cancerous patients. Meanwhile the miR-25 showed a different expression in related studies. Therefore, we summarize the results from a variety of studies using a meta-analysis, in order to explain the prognostic value of miR-25 in many human cancers. METHODS: The articles were retrieved from the on-line databases, PubMed, EMBASE and CNKI. We extracted and estimated the hazard ratios (HRs) for overall survival (OS), which compared the high and low expression levels of miR-25 in patients with a different of cancers. Pooled HRs and 95% confidence intervals (CIs) were calculated. RESULTS: Eight studies of 868 patients were selected into the final meta-analysis after a strict filtering and qualifying process. Fixed model or random model method was chosen depending on the heterogeneity between the studies. For OS, higher miR-25 expression could significantly predict worse outcome with the pooled HR of 2.434 (95% CI 1.330-3.539, P=0.000). The subgroup analysis showed that high expressed miR-25 could worsen OS in Chinese patients with pooled HR of 1.895 (95% CI 1.096-2.693, P=0.007). The sensitive analysis showed that removing the document one by one, there no obvious change of HR of 0.823 (95% CI 0.385-1.260). No bias existed in the group. CONCLUSION: Our study indicates that high expression level of miR-25 corresponds with poor survival in cancerous patients, and the expression of miR-25 could be a promising prognostic biomarker in the future. PMID- 26550210 TI - Association between IL-17F rs763780 polymorphism and susceptibility of asthma: a meta-analysis. AB - Published data on the association between interleukin-17F (IL-17F) rs763780 polymorphism and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, Elsevier, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates and funnel plots were inspected for indication of publication bias. Seven studies with a total of 4200 subjects were finally identified. Overall, we found no significant association between IL-17F rs763780 polymorphism and asthma susceptibility (G vs. A: OR = 1.08, 95% CI = 0.81-1.44, P = 0.62; GA vs. AA: OR = 1.11, 95% CI = 0.84-1.47, P = 0.47; GG + GA vs. AA: OR = 1.07, 95% CI = 0.79 1.44, P = 0.65). After categorizing studies into different subgroups on the basis of ethnicity and age, there remained no significant association (all P > 0.05). Sensitivity analysis demonstrated the stability of our results and publication bias was not evident. The present meta-analysis, combining all currently available data, suggests that IL-17F rs763780 polymorphism is not associated with the susceptibility of asthma. PMID- 26550211 TI - Effects of combined alendronate and alfacalcidol on prevention of fractures in osteoporosis patients: a network meta-analysis. AB - BACKGROUND: Published literatures report controversial results about the effect of combined treatment with alendronate and alfacalcidol for the prevention of fractures in osteoporosis patients. METHODS: Seven common databases were searched for related randomized controlled trials published up to April, 2015. Bayesian random effects network meta-analysis was used to assess the pairwise odds ratios (OR), 95% credible intervals (CI). RESULTS: Thirteen randomized controlled trials were identified (3710 patients). The network meta-analysis results indicated that combining treatment with alendronate and alfacalcidol was significantly better to prevent bone fractures in osteoporosis patients than alendronate (OR=0.53, 95% CI: 0.19-0.95) and alfacalcidol (OR=0.25, 95% CI: 0.08-0.49). In addition, there was no significant difference for adverse events among the three therapeutic regimen. CONCLUSIONS: Combined treatment with alendronate and alfacalcidol was more active than the monotherapies in preventing bone fractures in osteoporosis patients. Large-scale randomized, controlled trials are recommended to confirm the result. PMID- 26550212 TI - Comparison of dietary energy and macronutrient intake at different levels of glucose metabolism. AB - The aim of this study was to evaluate energy and glycolipid metabolism by determining the intake of energy and macronutrients in persons with differing glucose metabolisms. In total, 147 patients who were newly diagnosed with pre diabetes, 177 patients with diabetes, 139 patients who were previously diagnosed with diabetes, and 140 patients with normal blood sugar were selected from the 103rd Regiment of Xinjiang. All patients had Han nationality and were over 30 years old. Their energy and macronutrient intakes were analyzed from data obtained from a 3-day food weighing household investigation. Compared to the normal group, the patients in the previously and newly diagnosed diabetic groups were older, less educated, and had a greater prevalence of hypertension (P<0.05). Compared to the normal group, patients with abnormal glucose metabolism had larger waist circumferences; higher systolic and diastolic blood pressure; higher postprandial glucose; higher total cholesterol; lower high-density lipoprotein cholesterol (HDL-C; P<0.05); higher intakes of energy, carbohydrates, and fat; and lower intakes of protein and fiber. In addition, the newly and previously diagnosed patients had higher fasting glucose levels (P<0.05). Compared to the normal group, patients with abnormal glucose metabolism in each sex subgroup also had larger waist circumferences, and more men had abdominal obesity (P<0.05). Diabetes or pre-diabetes patients had a higher intake of energy, carbohydrates, and fat, but a lower intake of proteins and fiber. They had severe abdominal obesity, a greater prevalence of hypertension, higher total cholesterol levels, lower HDL-C, and poor blood glucose and glycosylated hemoglobin levels, especially postprandial plasma glucose levels. PMID- 26550213 TI - Biocompatibility and drug release behavior of chitosan/poly (vinyl alcohol) corneal shield in vivo. AB - Backgound: Chitosan/polyvinyl alcohol corneal cap has good biocompatibility and drug slow release characteristics, which provided new treatment method for anterior segment disease. Our study was to evaluate biocompatibility of poly (vinyl alcohol)/chitosan corneal shield's intraocular and investigate its feasibility to treat ocular surface disorders. METHODS: Thirty-six white rabbits were randomly divided into four groups. Slit lamp observation were conducted at 1, 3, 7 and 10 days after operation. Corneal and conjunctiva tissue harvested from the experimental groups was observed by HE staining 10 days after operation. The aqueous humor was aspirated from the anterior chamber at each designated time point (1, 3, 7 and 10 days). The cornea and conjunctive were collected at 10 days. The concentration of each tissue was analyzed by ultra-performance liquid chromatography and microscope observation. RESULTS: In all groups, mild hyperemia was observed 1 day after operation, and there was no obvious inflammatory reaction occurring on the seventh and tenth day. No corneal edema and inflammatory reaction of anterior chamber occurred till the tenth day. For histopathology, there was no obviously mild chronic and inflammatory reaction occurred, and no significant difference between the corneal shield with-in groups and with-out groups. The drug concentrations in corneal and conjunctival in group (A, B) were significantly lower than eye drops in the control group (C, D), and blank corneal cover in group C was significantly sham operation in group D. CONCLUSION: The results indicated that the proposed membrane combined with ophthalmic solution has substantial potential as ocular delivery system. PMID- 26550214 TI - Molecular mechanism of HEIH and HULC in the proliferation and invasion of hepatoma cells. AB - OBJECTIVE: To study the expression and molecular mechanism of long noncoding RNAs (lncRNA) including HEIH and HULC in proliferation and invasion of hepatoma cells. METHODS: We detected the expression of HEIH and HULC in hepatocellular carcinoma cell line (MHCC97L and HepG2), as well as in human normal hepatocyte line (cHL 7702) by real-time PCR. Using MTT and transwell, we investigated the effect of HEIH and HULC on proliferation and invasion of hepatoma cells with siRNA and expression plasmid. To explore the molecular mechanism, we use western blot to reveal the role of HEIH and HULC in tumor invasion related gene expression. RESULTS: The expression of HEIH and HULC in hepatocellular carcinoma cell line was significantly increased compared with human normal hepatocyte line (P<0.05). The expression of HULC in HepG2 was higher than that in MHCC97L. The over expression of HULC could enhance proliferation of MHCC97L and HepG2, however, the over-expression of HEIH could not. The over-expression of HULC and HEIH could promote invasion of MHCC97L and HepG2. Invasion of MHCC97L and HepG2 did not have significant change after down-regulating of HEIH and HULC by siRNA. Over expression of HULC up-regulated the expression of Snail in HepG2. CONCLUSIONS: The expression of HEIH and HULC increased significantly in hepatocellular carcinoma cell line compared with that in human normal hepatocyte line. HULC could promote proliferation of hepatoma cells. HEIH and HULC play an important role in the invasion of hepatocellular carcinoma cell. PMID- 26550215 TI - Comparison of the efficacy and safety of laparoscopic-assisted operations and open operations for Hirschsprung's disease: evidence from a meta-analysis. AB - PURPOSE: To determine the efficacy and safety of laparoscopic-assisted operations compared with open operations, used for the treatment of Hirschsprung's disease (HD). METHODS: Pertinent studies were identified by searching of PubMed and Web of Science. We analyzed dichotomous variables by estimating odds ratios (OR) with their 95% confidence interval (CI) and continuous variables using the weighted mean difference (WMD) with the 95% CI. The random effect model was used to combine the results. RESULTS: Nine articles involving a total of 421 patients were included in this meta-analysis. For operation time of patients with HD, pooled data demonstrated a significantly shorter time in the laparoscopic operations group compared with open operations group (WMD = -0.27, 95% CI = 0.49, -0.05). The intraoperative blood loss was fewer in the laparoscopic operations group than open operations group (WMD = -1.05, 95% CI = -1.56, -0.54). The length of postoperative hospital was significantly shorter in the laparoscopic operations group. The number of complications was significantly lower in laparoscopic operations group than open operations group. CONCLUSIONS: Our results suggested that laparoscopic-assisted operation is generally safer and more reliable than open operation for patients with HD. PMID- 26550216 TI - The role of great auricular-facial nerve neurorrhaphy in facial nerve damage. AB - BACKGROUND: Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. METHODS: Rat models of facial nerve cut (FC), facial nerve end to end anastomosis (FF), facial-great auricular neurorrhaphy (FG), and control (Ctrl) were established. Apex nasi amesiality observation, electrophysiology and immunofluorescence assays were employed to investigate the function and mechanism. RESULTS: In apex nasi amesiality observation, it was found apex nasi amesiality of FG group was partly recovered. Additionally, electrophysiology and immunofluorescence assays revealed that facial-great auricular neurorrhaphy could transfer nerve impulse and express AChR which was better than facial nerve cut and worse than facial nerve end to end anastomosis. CONCLUSIONS: The present study indicated that great auricular-facial nerve neurorrhaphy is a substantial solution for facial lesion repair, as it is efficiently preventing facial muscles atrophy by generating neurotransmitter like ACh. PMID- 26550217 TI - Cytotoxic effects of beta-carboline alkaloids on human gastric cancer SGC-7901 cells. AB - To investigate the cytotoxic effects of beta-carboline alkaloids on human gastric cancer SGC-7901 cells. Human gastric cancer SGC-790s1 cells were treated with beta-carboline alkaloids at the concentration of 0, 10, 20, 30 and 40 MUg/ml for 48 hr. Cell viability was measured by Cell Counting Kit-8 assay. Cell apoptosis was detected by Hoechst 33258 staining and DNA fragmentation analysis. The expression of phosphatase and tensin homolog (PTEN) and extracellular signal regulated kinase (ERK) was examined by quantitative real-time PCR (qRT-PCR) assay and western blot analysis. beta-carboline alkaloids inhibited the growth of SGC 7901 cells concentration dependently. beta-carboline alkaloids treated SGC-7901 cells displayed apoptotic nuclei as detected using Hoechst 33258 staining. beta carboline alkaloids also induced DNA ladder, indicative of apoptosis in SGC-7901 cells concentration-dependently. Furthermore, beta-carboline alkaloids increased PTEN and decreased ERK mRNA expression in SGC-7901 cells in a concentration dependent manner. They also increased PTEN and decreased ERK protein expression. beta-carboline alkaloids inhibit the growth and induce apoptosis of SGC-7901 cells. The cytotoxic effects of beta-carboline alkaloids might correlate with increased PTEN expression and decreased ERK expression in SGC-7901 cells. PMID- 26550218 TI - Association of CCND1 gene polymorphism with cervical cancer susceptibility in Caucasian population: a meta-analysis. AB - OBJECTIVE: To study G870A polymorphism in CCND1 gene and the risk of cervical cancer susceptibility in Caucasian population by meta-analysis. METHODS: Search the correlative study of G870A polymorphism in CCND1 gene and cervical cancer susceptibility in PubMed and EMBASE database, and extract the reference data according to the including criteria. We used RevMan 5.2 software to merge the OR value and 95% confidence interval and to perform meta-analysis. RESULTS: Five case-control studies were enrolled into the analysis, including 1665 patients with cervical cancer and 2511 healthy people as control. It was revealed by meta analysis that, in the Caucasian population, there was no significant correlation between G870A polymorphism in CCND1 gene and the risk of cervical cancer (G allele vs. A: OR = 1.01, 95% CI = 0.80-1.27, P = 0.95; AA vs. GA + GG: OR = 1.13, 95% CI = 0.98-1.30, P = 0.10; (GA + AA) vs. GG: OR = 1.15, 95% CI = 0.72-1.85, P = 0.55). CONCLUSION: G870A polymorphism in CCND1 gene may be uncorrelated with the development of cervical cancer in Caucasian population. PMID- 26550219 TI - Effects of combined thymosin and hydrocortisone on immune response in septic mice. AB - This study is to investigate the effects of the thymosin alpha1 (Talpha1) and hydrocortisone (HC) combination treatment on the immune responses in septic mice. According to different treatments, mice were divided into the control group (n = 18), the sepsis model group (n = 18), the Talpha1 group (n = 18), the HC group (n = 18), and the Talpha1+HC group (n = 18). Septic mouse model was established by the intraperitoneal injection of lipopolysaccharide (LPS). At 72 h after modeling, flow cytometry was used to analyze the dendritic cell (DC) numbers in peripheral blood and the expressions of MHC II and CD86. Tumor necrosis factor alpha (TNF-alpha) level was measured by ELISA. Treatments of Talpha1 and/or HC dramatically increased the survival rates of LPS-induced septic mice. Flow cytometry showed that, the DC numbers in peripheral blood were significantly decreased in the sepsis model group, which could be dramatically elevated by Talpha1 treatment alone and in combination with HC (Talpha1+HC). However, the DCs were undetectable in the HC group. In addition, the MHC II expression level was decreased in the sepsis model group, which was further declined in the Talpha1 and Talpha1+HC groups. The expression level of CD86 was elevated in the model group, which could be significantly down-regulated by the treatments of Talpha1 and Talpha1+HC. ELISA showed that, the peripheral blood TNF-alpha level in the HC group was lower than in the sepsis model group. Compared with the sepsis model group, the TNF-alpha levels were significantly elevated in the Talpha1 and Talpha1+HC groups. Talpha1 and HC combination treatment could improve the immune function and regulate the inflammatory response to increase the survival rates of LPS-induced septic mice. PMID- 26550220 TI - Protection effect of survivin protein overexpression on acute myocardial infarction in rats. AB - To investigate the protective effect of adenovirus mediated Survivin protein overexpression on acute myocardial infarction in rats. 45 acute myocardial infarction rat models were constructed by suture method and were randomly divided into sham group, model group and treatment group. The treatment group was injected with Survivin gene packed virus via ventricle. The model group was injected with equal titer of adenovirus packed empty vector. The sham group was not ligated. These rats were killed in 96 h after treatment. The levels of Survivin, Caspase-3, caspase-7 mRNA and protein in myocardial tissues were detected by real-time fluorescence quantitative PCR and Western blot. Myocardium tissue cell apoptosis were analyzed by TUNEL staining, the immunology of myocardial infarction tissue was analyzed by TTC staining. Compared with model group and sham group, the level of survivin protein in myocardium tissue of rats in treatment group was significantly increased (P<0.05). Compared with sham group, the levels of caspase-3 and caspase-7 mRNA and protein in myocardial tissue of rats in model group and treatment group were significantly increased, but the treatment group were significantly lower than those of model group (P<0.05). The myocardium cell apoptosis index and myocardial infarction areas of rats in model group and treatment group were significantly higher than those of sham group, but the treatment group were significantly lower than those of model group (P<0.05). In conclusion, Survivin protein overexpression in myocardial tissue can significantly inhibit the expression of apoptosis promoting factor in myocardial tissue of acute myocardial infarction rats, reduce the apoptosis index of myocardial cells and the myocardial infarct size, which has great significance for protecting myocardial function. PMID- 26550221 TI - Abductor digiti minimi muscle flap transfer to prevent wound healing complications after ORIF of calcaneal fractures. AB - OBJECTIVES: To examine the transfer of abductor digiti minimi (ADM) muscle flaps as a method for preventing wound healing complications in cases of closed calcaneal fractures treated with open reduction and internal fixation (ORIF). METHOD: DESIGN: Retrospective review. PATIENTS: Twenty-six cases of acute closed calcaneal fracture in patients at risk for serious wound complications or with serious fractures. INTERVENTION: During the ORIF surgery, an ADM muscle flap was removed and used to cover the plate, filling the gap between the plate and skin. MAIN OUTCOME MEASURES: Wound healing rates, postoperative complications, and time to heal. RESULTS: All wounds healed uneventfully, except for one case of minor superficial epithelial necrosis during the early postoperative period, which was treated conservatively. All patients regained ambulatory status with regular foot apparel. At last follow-up, the patients presented no clinical, laboratory, or radiological signs of complications. CONCLUSIONS: This ADM muscle flap transfer technique appeared to successfully prevent wound healing complications among patients undergoing ORIF for closed calcaneal fractures. This method offers a promising treatment option for calcaneal fractures in patients at high risk for serious wound complications, and future studies with greater numbers of cases are needed to further investigate its clinical application. PMID- 26550222 TI - Short interfering RNA directed against the GOLPH3 gene enhances the effect of chemotherapy against oral squamous cell carcinoma by regulating Caspase3, Bcl2 and cytochrome-c expression. AB - Growing evidence reported that Golgi phosphoprotein 3 (GOLPH3) was involved in the progression of several human cancers. To determine whether knockout of GOLPH3 enhances the effect of Chemotherapy against cell growth of oral squamous cell carcinoma in vitro. OSCC cells were transfected with Golph3 plasmid, Golph3-RNAi and the relative control plasmids. Transfected Tca-8113 cells treated with cis Dichlorodiamineplatinum (DDP; 0, 0.05, 0.25, 1.25, 6.25 and 31.25 ug/ml) or Paclitaxe (0, 2, 10, 50, 250 and 1250 nM) or Adriamycin (0, 0.25, 0.5, 1, 2 and 4 ug/ml) for 24 h, respectively, was determined using MTT assay. Apoptosis-related protein expression Cytochrome-C, Caspase3 and Bcl-2 was analyzed by RT-PCR and western blots. Result of MTT showed that Golph3-RNAi transfected Tca-8113 cells enhanced the effect of chemotherapy, and the effect was strengthened with the increasing concentration of drugs, and the Golph3 plasmid transfected Tca-8113 cells showed the opposite effect. RT-PCR and western blots assays revealed that expression of cytochrome-C and caspase3 were up-regulated, while Bcl-2 expression was down-regulated in Golph3-RNAi transfected Tca-8113 cells. Taken together, this study demonstrated that GOLPH3 had potent pro-tumor growth and decreased the effect of Chemotherapy, and its mechanism is primarily via cell anti-apoptosis, down-regulating the expression of cytochrome-C and caspase3, up-regulating Bcl-2 expression. PMID- 26550223 TI - Laparoscopic surgery for removal of choledochal cysts and Roux-en-Y anastomosis. AB - Choledochal cyst is prevalent in female than male. Diagnosis and management of choledochal cyst is important in clinical practice, or else, patients may develop cholangiocarcinoma. Currently, complete resection is the standard method for the treatment of choledochal cyst. However, traditional open surgery is usually needed in these procedures, which may induce postoperative injuries. In this case, we present our experiences for the management of choledochal cyst through radical removal combined with Roux-en-Y anastomosis under laparoscope. Our procedures are minimally invasive and the outcomes are satisfactory during the follow up. PMID- 26550224 TI - The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. AB - To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease. PMID- 26550225 TI - Association of DNMT3B -283 T > C and -579 G > T polymorphisms with decreased cancer risk: evidence from a meta-analysis. AB - Numerous studies have explored the association of polymorphisms in the DNA methyltransferase 3b (DNMT3B) gene with the risk of different types of cancer, but yielded controversial results. Therefore, we performed a meta-analysis to derive a more precise estimation of the association between three widely-studied DNMT3B polymorphisms and overall cancer susceptibility. Totally, 4 studies with 1234 cases and 1337 controls were eligible for DNMT3B -283 T > C (rs6087990), 19 studies with 5332 cases and 7407 controls for DNMT3B -149 C > T (rs2424913), and 14 studies with 3933 cases and 4436 controls for DNMT3B -579 G > T (rs1569686). Overall, DNMT3B -283 T > C was associated with a significantly reduced risk of overall cancer (T vs. C: OR = 0.84, 95% CI = 0.71-0.99, P = 0.039). Likewise, the association of DNMT3B -579 G > T with a decreased overall cancer risk was also observed (heterozygous: OR = 0.77, 95% CI = 0.65-0.91, P = 0.003 and dominant: OR = 0.80, 95% CI = 0.66-0.98, P = 0.029); in the subgroup analysis, the protective association was found for lung and colorectal cancer, but not for head and neck cancer. Finally, the pooled analysis showed no significant association between DNMT3B -149 C > T and overall cancer susceptibility, but stratification analysis indicated that this polymorphism decreased the risk of developing head and neck cancer (heterozygous: OR = 0.73, 95% CI = 0.59-0.90, P = 0.003 and dominant: OR = 0.76, 95% CI = 0.61-0.93, P = 0.009). In conclusion, our results suggested that DNMT3B -283 T > C and DNMT3B -579 G > T but DNMT3B -149 C > T might confer protection against overall cancer risk. In the future, large and well-designed case-control studies are needed to validate our findings. PMID- 26550226 TI - Evaluation of three-dimensional printing for internal fixation of unstable pelvic fracture from minimal invasive para-rectus abdominis approach: a preliminary report. AB - OBJECTIVE: The aim of this study is to evaluate the efficacy and feasibility of three-dimensional printing (3D printing) assisted internal fixation of unstable pelvic fracture from minimal invasive para-rectus abdominis approach. METHODS: A total of 38 patients with unstable pelvic fractures were analyzed retrospectively from August 2012 to February 2014. All cases were treated operatively with internal fixation assisted by three-dimensional printing from minimal invasive para-rectus abdominis approach. Both preoperative CT and three-dimensional reconstruction were performed. Pelvic model was created by 3D printing. Data including the best entry points, plate position and direction and length of screw were obtained from simulated operation based on 3D printing pelvic model. The diaplasis and internal fixation were performed by minimal invasive para-rectus abdominis approach according to the optimized dada in real surgical procedure. Matta and Majeed score were used to evaluate currative effects after operation. RESULTS: According to the Matta standard, the outcome of the diaplasis achieved 97.37% with excellent and good. Majeed assessment showed 94.4% with excellent and good. The imageological examination showed consistency of internal fixation and simulated operation. The mean operation time was 110 minutes, mean intraoperative blood loss 320 ml, and mean incision length 6.5 cm. All patients have achieved clinical healing, with mean healing time of 8 weeks. CONCLUSION: Three dimensional printing assisted internal fixation of unstable pelvic fracture from minimal invasive para-rectus abdominis approach is feasible and effective. This method has the advantages of trauma minimally, bleeding less, healing rapidly and satisfactory reduction, and worthwhile for spreading in clinical practice. PMID- 26550228 TI - Sonographic assessment of placental location: a mere notional description or an important key to improve both pregnancy and perinatal obstetrical care? A large cohort study. AB - During a standard obstetrical sonogram, the assessment of placental location (PL) is often limited to a mere notional description without formulating any association to possible implications on pregnancy and childbirth. The aim of the study was to speculate if different sites of PL may have a role in influencing fetal presentation-(FP) at birth and if certain pregnancy-complications may be more closely associated with one rather than with another PL. We conducted an observational-prospective-cohort study on pregnant women referred to the Ob/Gyn Unit of Padua University for routine third-trimester ultrasound scan. For all eligible patients we evaluated the correlation between sites of PL and perinatal maternal/fetal outcomes. Non-cephalic presentation was found in 1.4% of anterior, 8.9% of posterior, 6.2% of fundal and 7.2% of lateral insertions. FP at the beginning of the third trimester as opposed to presentation at birth was concordant in 90.3% of anterior, 63.3% of posterior and 76.5% of lateral insertions. Considering only non-cephalic fetuses we observed a decreasing probability for spontaneous rotation in the following lies: 88% anterior-PL, 80% posterior-PL, 77% lateral-PL, and 70% fundal-PL. Patients with posterior-PL (significantly associated with previous-CS) had a significantly higher CS-rate (due to previous-CS and breech-presentation). Significant differences were found in terms of gestational-hypertension and fresh-placental-weight between different sites of PL. In conclusion our data showed that an understanding of the role that PL plays in influencing the incidence of certain maternal-fetal conditions may assist Clinicians in improving perinatal maternal/fetal outcomes. PMID- 26550229 TI - Investigation of relationship of visceral body fat and inflammatory markers with metabolic syndrome and its components among apparently healthy individuals. AB - Metabolic syndrome is a cluster of disorders and great risk for cardiovascular diseases. We aimed to investigate association between severity of metabolic syndrome (MetS) and anthropometric measurements, and to evaluate correlation of MetS and its components with metabolic deterioration and inflammatory indexes. The cross-sectional study enrolled 1474 patients with obesity and overweight. The patients were grouped as MetS and Non-MetS, and were sub-grouped as group 1 (three criteria), 2 (four criteria) and 3 (>= five criteria) according to NCEP ATP III. Mean age was 38.7 +/- 11.9 years and BMI was 35.1 +/- 6.3 kg/m(2). Lipid profile, anthropometric and blood pressure measurements, liver function tests, bioelectric impedance body fat compositions, insulin resistance and HbA1c, and spot urinary albumin-creatinine ratio were significantly different between groups of MetS and Non-MetS. Age, lipid profile, bioelectric impedance fat analyses, BMI, blood pressure values, glucose, insulin resistance, uric acid and hs-CRP levels were significantly different between groups of MetS component groups. ROC analysis revealed that hs-CRP was found to be more predictive for severity of metabolic syndrome components 3 and 4 (P=0.030); uric acid and visceral fat were more actual to predict severity of metabolic syndrome between 3 and 5 MetS components, (P=0.006) and uric acid was detected as more actual to predict severity of MetS between 4 and 5 components (P=0.023). In conclusion, uric acid, hs-CRP and visceral body fat composition were useful to predict to severity of MetS in primary care. PMID- 26550227 TI - Diverting stoma with anterior resection for rectal cancer: does it reduce overall anastomotic leakage and leaks requiring laparotomy? AB - Anastomotic leakage (AL) after resection for rectal carcinoma accelerates morbidity and mortality rates, extends hospital stay, and increases treatment costs, particularly when requiring laparotomy. The role of a protective diverting stoma (DS) in avoiding leakage has repeatedly been discussed, but prospective randomized studies on this subject are rare and their results contradictory. The MEDLINE database was searched for studies of AL requiring laparotomy and of the associated rate of protective DSs in initial anterior resection (AR) to review these studies systematically. The collected data were used to determine the average rate of AL requiring laparotomy after rectal cancer surgery in the DS group compared with that in the non-DS group. A total of 930 abstracts were retrieved from MEDLINE; 15 articles on AR and 22 on low/ultralow AR (LAR) were included in the review and analysis. The overall rate of AL requiring laparotomy was 6.57% (813/12, 376) in the AR studies and 4.13% (157/3, 802) in the LAR studies. In the AR studies, the pooled AL rate in the DS group was higher than that in the non-DS group (12.30% vs. 9.16%, P < 0.001). However, the pooled rate of AL requiring laparotomy in the DS group was lower than that in the non-DS group (3.69% vs. 7.42%, P < 0.001). In the LAR studies, the pooled AL rate in the DS group was lower than that in the non-DS group (7.74% vs. 9.64%, P = 0.045). The pooled rate of AL requiring laparotomy in the DS group was also lower than that in the non-DS group (2.67% vs. 5.21%, P < 0.001). By contrast, the pooled rate of definitive stomas and mortality caused by AL did not have any statistical difference between the DS and non-DS groups in both AR studies (definitive stomas: 0% vs. 0.65%; mortality: 0.95% vs. 1.19%) and LAR studies (definitive stomas: 1.03% vs. 1.01%; mortality: 0.35% vs. 0.36%). Protective DSs significantly decrease the rate of AL in LAR. AL requiring surgical correction was significantly reduced in the DS group in both AR and LAR studies. Protective DSs did not affect the definitive stomas and mortality rate; this lack of an effect warrants further high-quality clinical trials. PMID- 26550230 TI - The management of filter-related caval thrombosis complicated by heparin-induced thrombocytopenia and thrombosis. AB - This report evaluates the efficiency and safety of catheter-directed thrombolysis (CDT) using tissue plasminogen activator (tPA) and argatroban for the treatment of IVC filter thrombosis complicated by heparin-induced thrombocytopenia (HIT). From October 2012 to December 2014, 19 patients with unilateral lower extremity deep venous thrombosis were treated with standard anticoagulation, filter placement and urokinase-based CDT, all of whom developed IVC filter thrombosis and HIT. A revised protocol (tPA-based CDT and argatroban-based anticoagulation) was performed to treat IVC thrombosis. The extent of lysis was graded from I to III. Technical and clinical outcomes and complications were monitored. A total of 22 filters were implanted, 20 of which were retrieved later. The technical success rate of revised CDT for IVC thrombosis was 100%. On evaluating IVC thrombus, thirteen cases (68.4%, 13/19) were identified as grade III (complete resolution of thrombus) and six (31.6%, 6/19) as grade II (50-99% resolution of thrombus). No major bleeding related to CDT occurred. HIT in all patients was successfully treated with argatroban. Two patients with malignant tumor died during the follow-up. For patients with IVC filter thrombosis complicated by HIT, it seems tPA-based CDT and argatroban is an alternative regimen. PMID- 26550231 TI - Metformin therapy and prostate cancer risk: a meta-analysis of observational studies. AB - OBJECTIVE: Several observational studies have shown that metformin therapy may modify the risk of prostate cancer. We carried out a meta-analysis of relevant studies evaluating the effect of metformin therapy on prostate cancer risk. METHODS: We searched pubmed database (January 1966-February 2014) for case control and cohort studies that assessed metformin therapy and prostate cancer risk. Two authors independently assessed eligibility and extracted data. Summary RRs was calculated using fixed-effects model or random-effects model. Heterogeneity among studies was examined using Q and I(2) statistics. RESULTS: We included six cohort studies and four case-control studies in the present meta analysis, comprising 863,769 participants and 39,073 prostate cancer cases. The pooled RR of prostate cancer in relation to metformin therapy was 0.92 (95% CI: 0.84-1.02, P = 0.112). When we stratified the various studies by study type, we found that metformin therapy was associated with a significant reduced risk of prostate cancer among cohort studies (RR = 0.92, 95% CI [0.87, 0.96], P<0.001); however, no significant association was detected among case-control studies (RR = 0.95, 95% CI [0.78, 1.16], P = 0.632). There was also no indication of publication bias as suggested by Begg's test (P = 0.421) and Egger's test (P = 0.627). CONCLUSION: Our findings indicate that metformin therapy is not significantly associated with lower prostate cancer risk. PMID- 26550232 TI - Echocardiographic evaluation of pulmonary venous blood flow and cardiac function changes during one-lung ventilation. AB - OBJECTIVES: The intra-pulmonary shunt induced by one-lung ventilation (OLV), is alleviated by increased pulmonary blood flow by gravitational redistribution and hypoxic pulmonary vasoconstriction. We investigated the changes of pulmonary venous blood flow (PVBF) and biventricular function during OLV with echocardiography. And the correlation between PVBF and intra-pulmonary shunt fraction (Qs/Qt) was evaluated. METHODS: PVBF of the left upper pulmonary vein and cardiac function were measured with echocardiography in twenty-five patients who underwent elective thoracic surgery in left lateral decubitus. Qs/Qt and PaO2 were measured with blood gas analysis. Data was obtained at 10 min after two-lung ventilation in supine (TLV-S) and lateral decubitus position (TLV-L), and at 10, 20 and 30 min after OLV in lateral decubitus position (OLV-10, -20 and -30). RESULTS: There were significant changes in PVBF among TLV-S, TLV-L and OLV-10 (959.5+/-280.8, 1416.9+/-489.7 and 1999.9+/-670.5 ml/min; P<0.05, respectively). There were not differences in PVBF, Qs/Qt and PaO2 among OLV-10, -20 and -30. There were an inverse correlation between percent change of PVBF and change of Qs/Qt (r(2) = 0.5; P<0.0001) and positive correlations between the percent change of PVBF and change of PaO2 (r(2) = 0.4; P<0.0001) during OLV over TLV-L. No significant changes in biventricular systolic and diastolic function were observed during positional change and OLV. CONCLUSIONS: A remarkable change of PVBF relevant to gravitational distribution and hypoxic pulmonary vasoconstriction was proved by echocardiography. And PVBF changes could represent the changes of Qs/Qt and PaO2 during OLV. However, biventricular function was not impaired during OLV. PMID- 26550233 TI - Co-transplantation of hippocampal neural stem cells and astrocytes and microvascular endothelial cells improve the memory in ischemic stroke rat. AB - BACKGROUND: Neural stem cells (NSCs) are promising for ischemia stroke because they can replace damaged or lost cells. However, the adult central nervous system (CNS) does not provide an optimal microenvironment for exogenous NSCs to survive, proliferation and differentiation. We established a co-transplantation system with NSCs and astrocyte and brain microvascular endothelial cells (BMECs) to explore whether it can improve the memory ability in ischemic stroke rat. METHODS: After building the ischemic stroke in 50 rats by middle cerebral artery occlusion and reperfusion (MCAO/R), transplantation of NSCs and astrocyte and BMECs were performed with different combination. RESULTS: Laser doppler flowmetry and MRI were used to detect the ischemia of the model and 42 rats survived for the Morris water-maze test. The test shows that co-transplantation with the three different cells together can improve memory deficits in MCAO/R rat and it is the most effect group. Grafting with two cells have more effect in memory improving than one cell while transplanting NSC alone has no obvious effect on memory improving. CONCLUSIONS: In NSC niche, astrocytes and BMECs are the most important cells to regulate and interaction with NSCs. Co-transplantation NSCs with astrocyte and BMECs can improve the memory ability in ischemia rat, which maybe the result of microenvironment improve by the astrocyte and BMECs. PMID- 26550234 TI - Diagnostic value of virtual touch tissue imaging quantification for benign and malignant breast lesions with different sizes. AB - The study was to explore diagnostic value of the virtual touch tissue imaging quantification (VTIQ) in distinguishing benign and malignant breast lesions of variable sizes. We performed conventional ultrasound and VTIQ in 139 breast lesions. The lesions were categorized into three groups according to size (group 1, <= 10 mm; group 2, 10-20 mm; and group 3, > 20 mm), and their mean, min, and max shear wave velocities (SWVs) were measured. Diagnoses were confirmed by pathological examination after surgery or needle biopsy. Receiver-operating characteristic curves (ROC) were constructed to determine the optimum cut-off values, calculate the area under curve (AUC), the sensitivity, specificity and accuracy for each velocity. For all groups, the mean, min, and max SWVs of malignant lesions were significantly higher than those of benign lesions (P < 0.05). The cut-off values of mean, min, and max SWVs were not significantly different among the three groups. In addition, the diagnostic performance of mean, min, and max SWV values is analogous, regardless of lesion size. In conclusion, VTIQ is a strong complement to conventional ultrasound, which is a promising method in the differential diagnosis of the breast lesions with different sizes. Further studies validate our results as well as reduce the number of unnecessary biopsies, regardless of size is warranted. PMID- 26550235 TI - Lentivirus-Mediated knockdown of tectonic family member 1 inhibits medulloblastoma cell proliferation. AB - Tectonic family member 1 (TCTN1) encodes a member of the tectonic family which are evolutionarily conserved secreted and transmembrane proteins, involving in a diverse variety of developmental processes. It has been demonstrated that tectonics expressed in regions that participate in Hedgehog (Hh) signaling during mouse embryonic development and was imperative for Hh-mediated patterning of the ventral neural tube. However, the expression and regulation of tectonics in human tumor is still not clear. In this study, shRNA-expressing lentivirus was constructed to knockdown TCTN1 in medulloblastoma cell line Daoy. The results showed that knockdown of TCTN1 inhibited cell proliferation and colony formation in Daoy cell line, also caused cell cycle arrest at the G2/M boundary. Taken all together, our data suggest that TCTN1 might play an important role in the progression of medulloblastoma. PMID- 26550236 TI - Vibration exercise decreases insulin resistance and modulates the insulin signaling pathway in a type 2 diabetic rat model. AB - Vibration exercise (VE) is a new type of physical training, but little is known about its effects on insulin resistance at the molecular level. A Sprague-Dawley rat model of type 2 diabetes with insulin resistance was induced with a high-fat diet and low-dose streptozotocin. Animals were then subjected to 8 wk of VE consisting of placing the rats on a vibration stand bracket (8 cm * 8 cm * 20 cm) with a maximum vertical vibration displacement of 52 mm for 15 min twice a day, 6 d each week. Various metabolic markers and the phosphorylation and expression of proteins within the PI3K/AKT insulin signaling pathway were assessed. The high fat diet and low-dose streptozotocin increased food intake, body weight, and levels of blood glucose, triglycerides, total cholesterol, and free fatty acids, while Kitt rate, 2-deoxyglucose uptake, and glycogen levels were decreased. These effects were ameliorated in animals receiving VE. VE treatment activated the PI3K/AKT insulin-signaling pathway, and also increased the expression of GLUT4. In conclusion, VE improved the metabolic issues associated with the diabetic state by suppressing the reduction of IRS1, AKT2, and GLUT4 in the diabetic condition, indicating that VE could be used as a therapeutic intervention for insulin resistance and type 2 diabetes. PMID- 26550237 TI - Imaging findings of bile duct hamartomas: a case report and literature review. AB - Bile duct hamartomas (BHs), also called von Meyenburg complex (VMC), are benign biliary malformations that originate from disorganization of the small intrahepatic bile ducts. This disorganization is often associated with the abnormal involution of embryonic ductal end plates in the liver. This is clinically significant, as the development of BHs can cause diagnostic confusion with liver metastases and small hepatocellular carcinoma (SHCC). Currently, we report a specific case of BHs and review the literature to better define and diagnose BHs. In the following case, a 37 year-old male bearing a lesion in his liver is presented and undergoes both radiological and pathological diagnosis. The lesion is preliminarily suspected to be a hepatic hemangioma by examination of conventional ultrasound (US), contrast enhanced ultrasound (CEUS), computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). However, SHCC is suspected by follow-up analysis of US and CEUS, due to the patient's background history of hepatitis B and growth of the lesion and a tumor feeding vessel in BHs via CEUS. However, BHs are finally diagnosed by biopsy pathology under the guidance of ultrasound. Therefore, we believe pathology is imperative for correct diagnosis of BHs over other similar diseases when the imaging findings are atypical. Here we report the novel and unique detection of a tumor-feeding vessel, which mimicked SHCC strongly, during the course of CEUS. We also present a comprehensive review of the previous reported radiological examination related to BHs. PMID- 26550238 TI - Osteogenic differentiation of CD271(+) cells from rabbit bone marrow cultured on three phase PCL/TZ-HA bioactive scaffolds: comparative study with mesenchymal stem cells (MSCs). AB - Tissue engineering is one of the major challenges of orthopedics and trauma surgery for bone regeneration. Biomaterials filled with mesenchymal stem cells (MSCs) are considered the most promising approach in bone tissue engineering. Furthermore, our previous study showed that the multi-phase poly [epsilon caprolactone]/thermoplastic zein-hydroxyapatite (PCL/TZ-HA) biomaterials improved rabbit (r) MSCs adhesion and osteoblast differentiation, thus demonstrating high potential of this bioengineered scaffold for bone regeneration. In the recent past, CD271 has been applied as a specific selective marker for the enrichment of MSCs from bone marrow (BM-MSCs). In the present study, we aimed at establishing whether CD271-based enrichment could be an efficient method for the selection of rBM-MSCs, displaying higher ability in osteogenic differentiation than non selected rBM-MSCs in an in vitro system. CD271(+) cells were isolated from rabbit bone marrow and were compared with rMSCs in their proliferation rate and osteogenic differentiation capability. Furthermore, rCD271(+) cells were tested in their ability to adhere, proliferate and differentiate into osteogenic lineage, while growing on PCL/TZ-HA scaffolds, in comparison to rMSCs. Our result demonstrate that rCD271(+) cells were able to adhere, proliferate and differentiate into osteoblasts when cultured on PCL/TZ-HA scaffolds in significantly higher levels as compared to rMSCs. Based on these findings, CD271 marker might serve as an optimal alternative MSCs selection method for the potential preclinical and clinical application of these cells in bone tissue regeneration. PMID- 26550239 TI - Comparison of photosynthesis and fluorescent parameters between Dendrobium officinale and Dendrobium loddigesii. AB - OBJECTIVE: To investigate the photosynthesis and fluorescent parameters between Dendrobium officinale and Dendrobium loddigesii, based on which to provide helpful information for the artificial cultivation of these cultivars. METHODS: Seeds were placed on the MS medium supplemented with 0.2 mg/L NAA, 2% (w/v) sucrose, 15% (v/v) potato extracts and powered agar (pH 5.8). Two months after germination, seedlings (n = 10) were transferred onto rooting medium containing MS medium supplemented with 0.5 mg/L NAA, 3% (w/v) sucrose, 20% (v/v) potato extracts and 10/00 (w/v) activated carbon (pH 5.8) in a glass bottle (6.5 cm in diameter and 9.5 cm in height) with a white transparent plastic cap. Chlorophyll content was determined using the UV-Vis spectrophotometric method. In addition, rates of oxygen evolution and uptake were measured. The chlorophyll fluorescence was determined at room temperature using PAM 2000 chlorophyll fluorometer (Heinz Walz GmbH, Germany). RESULTS: From month 5 to month 10, the overall contents of both chlorophyll a and chlorophyll b were higher in D. loddigesii compared with those in D. officinale. No statistical differences were observed in the apparent photosynthetic rate (APR) between D. loddigesii and D. officinale. No statistical difference was noticed in the Fo, Fm and Fv between D. loddigesii and D. officinale (P > 0.05). Significant increase was noticed in the oxygen consuming in PSI in month-8 and month-10 compared with that of month-6 in D. loddigesii. Nevertheless, in the D. officinale, the oxygen consuming in PSI in month-6 was remarkably increased with those of month-8 and month-10, respectively. CONCLUSIONS: The photosynthesis and fluorescence parameters varied in the seedling of D. loddigesii and D. officinale. Such information could contribute to the artificial cultivation of these cultivars. PMID- 26550240 TI - Genes associated with sodium fluoride-induced human osteoblast apoptosis. AB - This study aims to explore the potential pathways and molecular characteristics of fluorine-induced osteoblast apoptosis. In vitro fluorine-induced model was established with an osteogenesis sarcoma cell line Saos-2. Then flow cytometry was used to determine the mitochondrial membrane potential at 24 h after the intervention. 84 apoptosis-related genes in the cells were determined using the functional polymerase chain reaction (PCR) chip and part of the differentially expressed genes was verified with immune blotting. When the stimulated concentration of sodium fluoride were 20 mg/L, 40 mg/L and 80 mg/L, the mitochondrial membrane potential of the osteoblast cells were 27.0%, 28.8% and 38.6%, respectively, significantly higher than that in the blank control group (P<0.05). The PCR chip detection found 13 up-regulating genes and 15 down regulating genes, among which the expression of Bim, Caspase 9, Caspase 14, B cell lymphoma-2 (BCL2) and BAX increased with the doses of sodium fluoride, while the expression of Caspase 3 down-regulated in 5 mg/L sodium fluoride but up regulated at the concentration of sodium fluoride more than 10 mg/L. Caspase 7 expression showed no obvious difference between the different concentration groups. However, Caspase 10 decreased with the increasing doses of sodium fluoride. Fluoride-induced osteoblast apoptosis may be through the mitochondrial pathway (including endoplasmic reticulum stress pathway) and death receptor pathway. PMID- 26550241 TI - Effect of laryngeal mask airway placement on the optimal site and success rate of venipuncture via the right internal jugular vein. AB - The placement of a laryngeal mask airway (LMA) changes the relative positions of the common carotid artery (CCA) and right internal jugular vein (IJV), thereby affecting venipuncture via the right IJV. Therefore, we went on to determine the optimal site for puncturing the IJV after LMA-SupremeTM placement. In this study, forty-six patients were placed with a LMA-SupremeTM (size 3 or 4), and the right IJV was punctured at either of the three points (anterior, middle or posterior point). The CCA diameters and overlap between the right IJV and CCA were recorded before and after the LMA-SupremeTM placement. Finally, the success rates of IJV puncturing at the three aforementioned points were compared. We found that the size of the LMA-SupremeTM had no effect on patient respiration during the procedure. Overlap between the right IJV and CCA at the anterior and middle points was significantly increased after size 3 LMA-SupremeTM placements; Size 4 masks decreased the CCA diameters at the middle and posterior points, and significantly increased overlap between the right IJV and CCA at all the three points; IJV punctures performed after placement of size 3 LMA-SupremeTM had higher success rate than those performed after placement of size 4 masks, and were less likely to result in accidental arterial puncture. In conclusion, our study demonstrated that placement of size 3 LMA-SupremeTM caused little change in overlapping between the right IJV and CCA and the incidence of accidental arterial puncture; particularly for punctures performed at the posterior point. Therefore, we recommend venipuncture at the posterior point after placement of a LMA-SupremeTM. PMID- 26550242 TI - Association between IL-10 polymorphisms (-1082A/G, -592A/C and -819T/C) and oral cancer risk. AB - Interleukin-10 (IL-10) is likely to be closely correlated with the outbreak and progression of cancers though aiding tumors to free from the immune response. In previous studies, several polymorphisms sites including -1082A/G, -592A/C and 819T/C in the promoter region of IL-10 gene were proved to be involved in oral cancer. The purpose of this study was to further explore this association via a meta-analysis. There were four publications with 3783 cases and 4245 controls retrieved though electronic databases. The association among three IL-10 polymorphisms sites was estimated by summary odds ratios (ORs) and 95% confidence intervals (95% CIs) which were calculated using fixed-effect model. Subgroup analysis by ethnicity (Asian or Caucasian) was also performed for the analysis of IL-10-1082A/G polymorphism (three studies in Asians and one study in Caucasian). As a result, we found a moderately increased risk which was related to IL-10 1082A/G polymorphism in oral cancer under all the five contrasts [GG vs. AA: OR (95% CI)=2.95 (1.94-4.48); GG+AG vs. AA: OR (95% CI)=1.59 (1.35-1.86); GG vs. AG+AA: OR (95% CI)=2.59 (1.71-3.94); Allele G vs. Allele A: OR (95% CI)=1.68 (1.46-1.94); AG vs. AA: OR (95% CI)=1.53 (1.29-1.81)]. Additionally, the increased risk of oral cancer was also observed in Asians and Caucasians. However, the pooled data indicated that IL-10 -592A/C and -819T/C polymorphisms sites had no relationship with oral cancer risk. Taken together, the IL-10 1082A/G polymorphism site may act as a risk factor in oral cancer, and this issue still needs to be further verified. PMID- 26550243 TI - Plasma fibrinogen lever and risk of coronary heart disease among Chinese population: a systematic review and meta-analysis. AB - Coronary heart disease (CHD) remains the leading causes of death and disability for men and women in most developed countries. It may soon become the leading cause of death in developing countries. Several studies have examined the role of fibrinogen levels in the prediction of atherosclerosis and CHD events. The aim of this study was to explore the effects of plasma fibrinogen levels in Chinese patients with CHD and to examine the relationship of fibrinogen. We performed this meta-analysis of prospective studies of plasma fibrinogen level in relation to CHD risk in electronic database of Medline, EMBase, the Cochrane Library and CNKI (China National Knowledge Infrastructure). Plasma fibrinogen levels were calculated by mean difference with 95% confidence intervals (CI) in patients with CHD and related controls without CHD. The selected 23 studies included 2984 CHD cases and 2279 controls. Our results found that plasma fibrinogen levels of patients were significantly higher than control group (P<0.0001). The predicted odds ratio (OR) for a 1 g/L higher plasma fibrinogen level was 0.94 (95% CI=0.78 1.10). Furthermore, fibrinogen levels were slightly related to age-related CHD patients. The plasma fibrinogen lever was correlated with CHD in the Chinese population, and may be a risk factor and predictor of CHD. Further studies assessing any causal relevance of fibrinogen levels to disease are required. PMID- 26550244 TI - Expression of purinergic receptor P2Y4 in Schwann cell following nerve regeneration. AB - OBJECTIVE: Emerging evidences suggested an important role of purinergic receptor P2Y4 in nerve system. The present study aims to investigate the localization and possible function of P2Y4 receptor in recurrent laryngeal nerve (RLN) following regeneration. METHODS: Right RLN of fifty Sprague-Dawley rats was cut and immediately repaired with PLGA/chitosan nerve conduit. Immunofluorescence, real time qPCR and Western blot were used to detect the expression alterations of P2Y4 receptor. RESULTS: Weak immunostaining signals of P2Y4 receptor were located on the plasmalemma of Schwann cell (SC) with regular arrangement of axons in normal RLN. On the post-injury 4th day, the sprouting axons regrowed along the degenerated SCs intensively expressing P2Y4 receptor. On the post-injury 7th day, the regenerating axons existed in multicellular cords of P2Y4 receptor-positive SCs occupying the nerve gap. On the post-injury 14th day, the axons grew along the bands of P2Y4 receptor-positive SCs exhibiting the regularly parallel distribution. On the post-injury 30th day, mild immunostaining signals of P2Y4 receptor still existed on SC surface, and the regenerated axons were located inside the remodeled endoneurium tube. In accordance with immunofluorescence findings, the transcription and protein expression levels of P2Y4 were significantly increased after the injury and the peak value appeared on the post injury 7th day, compared to control group (P < 0.05). CONCLUSION: Data from the present study suggested a potential role of P2Y4 receptors in functional modulation of SCs in the regeneration of RLN. PMID- 26550245 TI - Chemokine (C-C motif) ligand 5 -28C>G is significantly associated with an increased risk of tuberculosis: a meta-analysis. AB - OBJECTIVE: Chemokine (C-C motif) ligand 5 (CCL5) has been shown to play an important role in antimycobacterial immune responses. Previous studies have extensively reported that the CCL5 -28C>G gene polymorphism is associated with susceptibility to tuberculosis (TB). However, the results of these studies have been inconsistent. To investigate the relationship between the CCL5 -28C>G and the risk of TB, we performed a meta-analysis. METHODS: We searched articles published before June 6, 2014 from PubMed, CNKI, and Wanfang databases. Data were extracted from all eligible publications independently by two investigators and statistically analyzed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the strength of the association between CCL5 polymorphism and TB. RESULTS: Four case-control studies including 647 TB cases and 726 controls were involved in the meta-analysis. Our meta-analysis indicated the CCL5 -28C>G gene polymorphism was significantly associated with increased risk of TB (G vs. C: 3.75, 95% CI = 1.76-7.99; GG vs. CC: OR = 30.26, 95% CI = 14.28-64.12). CONCLUSION: Our results suggested that the -28C>G polymorphism is significantly associated with higher TB risk, which is opposite from previously published reports. However, the number of the study is limited, additional well-designed studies are required to elucidate the association between the CCL5 -28C>G gene polymorphism and TB. PMID- 26550246 TI - Reduction of alpha1GABAA receptor mediated by tyrosine kinase C (PKC) phosphorylation in a mouse model of fragile X syndrome. AB - Fragile X syndrome (FXS) caused by lack of fragile X mental retardation protein (Fmr1) is the most common cause of inherited intellectual disability and characterized by many cognitive disturbances like attention deficit, autistic behavior, and audiogenic seizure and have region-specific altered expression of some gamma-aminobutyric acid (GABAA) receptor subunits. Quantitative real-time polymerase chain reaction and western blot experiments were performed in the cultured cortical neurons and forebrain obtained from wild-type (WT) and Fmr1 KO mice demonstrate the reduction in the expression of alpha1 gamma-aminobutyric acid (alpha1GABAA) receptor, phospho-alpha1GABAA receptor, PKC and phosphor-PKC in Fmr1 KO mice comparing with WT mice, both in vivo and in vitro. Furthermore, we found that the phosphorylation of the alpha1GABAA receptor was mediated by PKC. Our results elucidate that the lower phosphorylation of the alpha1GABAA receptor mediated by PKC neutralizes the seizure-promoting effects in Fmr1 KO mice and point to the potential therapeutic targets of alpha1GABAA agonists for the treatment of fragile X syndrome. PMID- 26550247 TI - BAMBI inhibits skin fibrosis in keloid through suppressing TGF-beta1-induced hypernomic fibroblast cell proliferation and excessive accumulation of collagen I. AB - Keloids are scars characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Hypernomic growth of fibroblast cells and excessive accumulation of collagens, especially collagen I, made important contribution to keloid formation. Transforming growth factor-beta 1 (TGF-beta1) was a key ruler for the dermal fibrosis. Here, we found that BMP and activin membrane-bound inhibitor (BAMBI), a pseudo-receptor of TGF-beta1, was being decreased during the human keloid development and in vitro keloid cell growth. To investigate the effect of BAMBI on keloid development, pcDNA-BAMBI expression vector were transfected into the human primary keloid cells. Then the cell proliferation and viability were detected with EdU and MTT methods and expression of TGF-beta1 and collagen I/III were examined by Western blotting analysis. The results showed that, compared to the control, BAMBI overexpression suppressed the cell proliferation and expression of TGF-beta1 and collagen I (P < 0.05), whereas, TGFbeta1 overexpression rescued the suppression. Finally, pcDNA-BAMBI expression vector was subcutaneously injected into transplanted human keloid in nude mice. During the 6 weeks of in vivo experiment, pcDNA-BAMBI injection significantly suppressed the growth of the implanted keloids and the ratio of collagen I in the keloids. Therefore, BAMBI had an effect on inhibition of keloid growth through suppressing TGF-beta1-induced fibroblast cell proliferation and excessive accumulation of collagen I. PMID- 26550248 TI - Correlation between expression of NF-E2-related factor 2 and progression of gastric cancer. AB - OBJECTIVE: Nuclear factor E2-related factor 2 (Nrf2) plays a part in antioxidant and phase II detoxification enzymes in cells by the up regulation of many antioxidant response elements (ARE) related gene transcription. Nrf2 not only protect the normal cells, but also can protect cancer cells from the effect of cell stress, which is helpful to the survival of cancer cell. Some studies show that the expression of Nrf2 has important clinical significance in cancer patients, but the analysis of gastrointestinal tumor Nrf2 comprehensive expression has not been reported. The aim of this study is to evaluate the expression of Nrf2 in gastric cancer by immunohistochemistry and analyze its related clinical significance. METHODS: 180 cases of gastric cancer patients receive the gastrectomy and lymphadenectomy, and the resection of tissue is expressesd in paraffin embedded sections by immunohistochemical analysis of Nrf2. And the difference between groups use chi(2) (chi-square criterion) test, and will be analyzed by Fisher's exact test and Mann-Whitney U test. Use univariate and multivariate analysis, Kaplan-Meier curve and log-rank to test and evaluate the correlation between the expression of Nrf2 and the clinical pathological features. RESULTS: The immune reaction of Nrf2 is mainly found in gastric cancer cell nucleus, which positive expression is closely related to the tumor size, depth of invasion, lymph node metastasis, lymphatic invasion and histological analysis (all P<0.05). The log-rank test shows that the survival rate of Nrf2 positive expression group is significantly lower than that of the negative expression group (P<0.01). The Nrf2 positive expression is closely related to the drug resistance of adjuvant chemotherapy on the basis of 5FU (P=0.022). CONCLUSION: There is a positive correlation between the expression of Nrf2 and the invasion of gastric cancer, which can be used as a potential indicator of patients' poor prognosis. PMID- 26550249 TI - Role of dendritic cell-mediated abnormal immune response in visceral hypersensitivity. AB - The role of dendritic cells (DCs) in irritable bowel syndrome (IBS) is unclear. This study tested the hypothesis that intestinal DCs induced visceral hypersensitivity in IBS rats through mast cell (MC) activation. The IBS rat model was established by combining colorectal distension with restraint stress. The number of CD103-positive cells in colon was higher in the IBS group. Expression of PAR-2, IL-4 and IL-9 in the colonic mucosa was higher in the IBS group. Mesenteric lymph node DCs (MLNDCs) and splenic CD4(+)/CD8(+) T cells were isolated and purified by a magnetic labeling-based technique; they were cultured alone or co-cultured (T4+DC/T8+DC). The coculture of MLNDCs and CD4(+) T cells had the highest IL-4 secretion in the IBS group, while IL-9 expression was higher in the cultures containing CD8(+) T cells. Our findings indicate that an increased number of DCs in the colon stimulated CD4(+) T cells to secrete high levels of IL-4, which led to the activation of MCs and subsequently resulted in visceral hypersensitivity. PMID- 26550250 TI - Relationships between genetic polymorphisms of E670G in PCSK9 gene and coronary artery disease: a meta-analysis. AB - OBJECTIVE: Proprotein convertase subtilisin-like kexin type 9 (PCSK9) gene E670G Polymorphism has been reported to be associated with coronary artery disease (CAD) and risk factors. However, the results remain controversial. We sought to perform a meta-analysis to investigate the relationships between genetic polymorphisms of E670G in PCSK9 gene and the risk of CAD. METHODS: Literature searches were performed to identify all published relevant case-control studies without any language restrictions. Meta-analysis was conducted using the Review Manager software (version 5.2). Heterogeneity was investigated and measured using Cochran's Q-statistic and the inconsistency index (I(2)) test; Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated. RESULTS: A total of 5 case-control studies among 871 patients with CAD and 1144 control subjects were included in the meta-analysis. we found a correlation between PCSK9 genetic polymorphisms and increased risk for CAD under all of the genetic model (allele model: OR: 1.56, 95% CI: 1.21-2.01, P < 0.001; dominant model: OR: 1.46, 95% CI: 1.14-1.88, P = 0.003; recessive model: OR: 3.46, 95% CI: 1.19-10.10, P = 0.02; homozygous model: OR: 3.89, 95% CI: 1.35-11.20, P = 0.01; Heterozygous model: OR: 1.43, 95% CI: 1.08-1.92, P = 0.01; respectively). CONCLUSION: The results of the meta-analysis indicated that genetic polymorphism of E670G in PCSK9 gene might be involved in pathogenesis of CAD; the 670G carriers may be closely related to the risk of CAD. PMID- 26550251 TI - Prostate stem cell antigen variation rs2294008 associated with the risk of bladder cancer. AB - Several studies reported Prostate stem cell antigen (PSCA) rs2294008 was susceptibly associated with bladder cancer (BC) risk. However, the results were not entirely consistent. The aim of this study was to investigate the association between rs2294008 and BC risk. Comprehensive meta-analysis was preformed to provide a more precise assessment of the association between rs2294008 and BC risk. Twenty five studies involving 14,244 BC patients and 53,963 controls were included in our meta-analysis. The crude odds ratios (ORs) and the 95% confidence intervals (95% CIs) were used to evaluate the strength of the association. Pooled results indicated that the PSCA variant rs2294008-T was significantly connected with an increased risk of BC (OR = 1.15, 95% CI = 1.12-1.18, P(z) < 0.0001). Moreover, stratified analyses showed that rs2294008 significantly increased BC risk in European (OR = 1.10, 95% CI = 1.05-1.15, P(z) < 0.0001), North American (OR = 1.18, 95% CI = 1.12-1.24, P(z) < 0.0001), and Asian (OR = 1.17, 95% CI = 1.13-1.22, P(z) < 0.0001). In conclusion, our meta-analysis demonstrated that the PSCA rs2294008 is a risk factor for BC in European, Asian and North American. Further large case-control studies are needed to assess the relationship in other populations. Biologically functional studies are needed to verify the molecular mechanisms in the pathogenesis of BC. PMID- 26550252 TI - Perineural invasion is an independent predictor of biochemical recurrence of prostate cancer after local treatment: a meta-analysis. AB - Controversy still existed regarding the role of perineural invasion (PNI) in prostate cancer. The present meta-analysis aimed to investigate the association between PNI and biochemical recurrence (BCR) of prostate cancer after local treatment. A systematic search of Medline, Embase and CENTRAL was performed for eligible studies. Pooled estimates of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were acquired by using the generic inverse variance method. Subgroup analyses were performed by the method treating prostate cancer including radical prostatectomy (RP) and radiotherapy (RT) as well as the specimens which were acquired from RP and biopsy. A total of 12 studies incorporating 5188 patients were included in the meta-analysis. Overall, PNI was significantly associated with BCR (HR 1.59, 95% CI 1.37-1.84). Similarly, a significant correlation between PNI and BCR was also found in RP series (HR 1.51, 95% CI 1.25-1.83) and RT series (HR 1.70, 95% CI 1.35-2.13). PNI predicted BCR of prostate cancer in both RP (HR 1.51, 95% CI 1.23-1.85) and biopsy specimens (HR 1.68, 95% CI 1.36-2.09). PNI was demonstrated to be associated with higher risk for BCR of prostate cancer after local treatment. Therefore, PNI should be considered when assessing the risk of BCR in prostate cancer, thereby to achieve the best treatment. PMID- 26550253 TI - Protective effects of low-dose rapamycin combined with valsartan on podocytes of diabetic rats. AB - The aim of this study was to study the impacts and the mechanisms of low-dose rapamycin combined with valsartan on the renal functions of diabetic nephropathy (DN) rats. 50 SD rats were randomly divided into the normal control group (group A, n=10) and the DN model group (n=40), the DN model group was intraperitoneally injected streptozocin (STZ) for the modeling, which were then equally divided into the DN group (group B), the rapamycin group (group C, orally administrated rapamycin 1 mg/kg/d), the valsartan group (group D, orally administrated valsartan 30 mg/kg/d) and the combined therapy group (group E, orally administrated rapamycin 1 mg/kg/d + valsartan 30 mg/kg/d). Group A and group B were orally administrated the same amount of 0.5% carboxymethylcellulose. After 8 week treatment, the rats of each group were killed for the renal functional and pathological detection, as well as the expression detection of nephrin and podocin of kidney tissues. Compared with group A, the renal functions of the DN model groups were all decreased, and the pathological changes were significant. Meanwhile, the expressions of nephrin/podocin were reduced (P<0.05); among which group B exhibited the most serious changes, while the situations of group E were improved after the combined treatment, the expressions of nephrin/podocin were increased. Low-dose rapamycin and valsartan could enhance the expressions of nephrin and podocin, reduce kidney damages, thus achieving the protective effects towards the kidneys, and the effects of the combined therapy were superior to those of monotherapy. PMID- 26550254 TI - Association of programmed death-1 gene polymorphism rs2227981 with tumor: evidence from a meta analysis. AB - To investigate the association of programmed death-1 gene polymorphism rs2227981 with tumor risk. The PubMed, Medline, Ovid Medline, EMBASE, Web of Knowledge were searched. Meta-analyses were conducted using RevMan 5.2.2 software. Total six researches involving in a total of 1427 tumor patients and 1811 healthy control people were included into this meta analysis. There was no association of PD-1 gene polymorphism with total tumor risk under four genetic models. (CT+TT vs CC, OR=1.09, 95% CI=0.80-1.49, P=0.59; CT+CC vs TT, OR=0.93, 95% CI=0.52-1.66, P=0.61; TT vs CC, OR=0.99, 95% CI=0.57-1.72, P=0.97; CT vs CC, OR=1.16, 95% CI=0.80-1.70, P=0.43). The sub-group analysis shown there were a significantly difference on association of PD-1 gene polymorphism with digestive system tumor risk between tumor patients and healthy control people, except recessive model. (CT+TT vs CC, OR=1.57, 95% CI=1.20-2.07, P=0.001; TT vs CC, OR=1.67, 95% CI=1.12 2.49, P=0.01; CT vs CC, OR=1.51, 95% CI=1.13-2.01, P=0.005). Moreover, the meta analysis results shown that there were association of PD-1 gene polymorphism with tumor risk under two models for the tumor specific occurring only in women. (CT+TT vs CC, OR=0.80, 95% CI=0.67-0.95, P=0.01; TT vs CC, OR=0.61, 95% CI=0.44 0.83, P=0.002). This study suggests that PD-1 gene polymorphism rs2227981 is associated with specific tumor types, including digestive system tumor and tumor specific occurring in woman. PMID- 26550255 TI - A comprehensive expression profile of micrornas in rat's pituitary. AB - MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that act as a negative regulator of most mRNAs. miRNAs influence the gene expression as transcriptional regulators and play an important role in many fundamental biological processes. It is generally acknowledged that miRNAs have a very important affection on mammalian pituitary. However, the answers of which role miRNAs play in the development of sexual function or how much they contribute to the pituitary function are not exactly. In our study, we used three female 21-day old rats and three female 12-month-old rats to analysis the function of miRNAs. By the analyses of microarray data, we finished the stem-loop real-time RT-PCR for the differentially expressed miRNAs. We detected a total of 93 differentially expressed miRNAs between 21-day-old rats' pituitary and 12-month-old rats'. Stem loop real-time RT-PCR suggests that the obtained data is of high credibility. Among these miRNAs, 7 miRNAs' expression (rno-miR-880, rno-miR-503, rno-miR-125a 3p, rno-miR-3596b, rno-miR-30e, rno-miR-214 and rno-miR-22) are significant different (P<=0.05). In a word, this study identified a number of specific changes in the expression of miRNAs, in rats by detecting the expression profile of miRNAs in rat's pituitary, and all of that lay the foundation for elucidating the regulatory mechanisms of miRNAs in rat's reproduction process. These differentially expressed miRNAs may play a very important role in rat's reproduction process. PMID- 26550256 TI - Up-regulation of serum miR-744 predicts poor prognosis in patients with nasopharyngeal carcinoma. AB - BACKGROUND: MiRNAs has been shown to be implicated in the pathogenesis of many human diseases including cancer. Dysregulation of miR-744 is common in a number of cancers, indicating miR-774 might be closely correlated with the tumorigenesis process. However, the role and clinical significance of miR-774 in nasopharyngeal carcinoma (NPC) is poorly known. Thus the aim of this study is to investigate whether there was any clinical value of serum miR-744 in detecting and predicting the prognosis of NPC. MATERIALS AND METHODS: Real-time PCR was used to examine the expression level of serum miR-744 in patients with NPC and the healthy volunteers. The changes in serum miR-744 expression level of NPC patients after receiving chemo-radiotherapy were also evaluated. The association between pre treatment serum miR-744 expression level and NPC clinicopathological parameters was investigated. Finally we employed Kaplan-Meier method and Cox proportional hazards model to evaluate the clinical value of serum miR-744 in predicting the prognosis of NPC. RESULTS: Our study showed the expression level of serum miR-744 was significant higher in patients with NPC in comparison with healthy controls (P<0.01). The serum miR-744 expression level was down-regulated significantly in NPC patients after receiving chemo-radiotherapy (P<0.01). The Pre-treatment Serum miR-744 expression level was correlated with various important NPC clinicopathological parameters including N stage, clinical stage and grade. In addition, NPC patients with higher serum miR-744 expression had poorer 5 year overall survival rate and relapse-free survival rate. What was more, serum miR 744 was showed to be an independent factor for predicting the prognosis of NPC. CONCLUSION: Serum miR-744 was up-regulated in NPC patients. Higher expression level of serum miR-744 was closely correlated with was associated with poor prognosis in NPC and it might be employed as a potential biomarker for predicting the clinical outcome of NPC patients. PMID- 26550257 TI - The protective effect of intraperitoneal medical ozone preconditioning and treatment on hepatotoxicity induced by methotrexate. AB - The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone preconditioning was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-alpha, IL-1beta, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone preconditioning and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats. PMID- 26550258 TI - A randomized controlled trial to assess the efficacy and safety of doubling dose clopidogrel versus ticagrelor for the treatment of acute coronary syndrome in patients with CYP2C19*2 homozygotes. AB - BACKGROUND: Compared with non-reversible, indirect P2Y12 inhibitor clopidogrel, ticagrelor is a reversible, direct acting inhibitor. The CYP2C19*2 allele is a common genetic variant in individuals that need given higher clopidogrel in acute coronary syndrome patients. OBJECTIVE: We aimed to assess a pharmacogenetic approach of doubling dose clopidogrel compare with standard dose of ticagrelor among carriers with the CYP2C19*2 homozygotes. MATERIALS AND METHODS: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) with clopidogrel (600 mg loading dose, 150 mg daily thereafter) for the prevention of cardiovascular events in CYP2C19*2 homozygotes patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. RESULTS: After genetic test to identify carriers of the CYP2C19*2 allele from 2295 patients, 224 cases with CYP2C19*2 homozygotes were enrolled into our prospective, randomized trial. Patients were random assignment with colpidogrel group (n = 112) and ticagrelor group (n = 112). The two groups were similar in terms of baseline characteristics. After the first 600 mg loading dose of clopidogrel, patients carrying two CYP2C19*2 allele had weaker PRU inhibition (39.8+/-37.4 vs 27.9+/-12.4; P = 0.001) and more bleeding adverse events (20.5% vs. 7.1%; hazard ratio = 2.88; 95% [CI], 1.34-6.15; P = 0.001) compared to those taking standard dose of ticagrelor. CONCLUSIONS: In CYP2C19*2 carriers with ACS, ticagrlor is as effective as high clopidogrel in reducing platelet reactivity, particularly in first days. This study suggests that ticagrelor may be much better than doubling dose clopidogrel in patients with CYP2C19*2 in according to platelet reactivity monitoring. Use of ticagrelor instead of clopidogrel may eliminate the need for genetic testing and lead to less mild bleeding adverse. PMID- 26550259 TI - Association between serum ferritin levels and metabolic syndrome: an updated meta analysis. AB - It is definite that the serum iron level has a positive correlation with the risk of obesity. However, the association between increased serum ferritin levels and the metabolic syndrome still remains controversial. The purpose of this meta analysis is to confirm the association between serum ferritin levels and metabolic syndrome. We searched PubMed and the China National Knowledge Infrastructure (CNKI) for relevant articles that assessed the association between serum ferritin levels and metabolic syndrome and were published between 2006 and 2014. Review Manage 5.3 software was used to collect and analysis the data cited in the ultimately selected papers. The variance was exhibited using the forest plot and the heterogeneity among studies was examined using the I(2) index. We use the funnel plot to evaluate the publication bias. Cross-sectional study, case control study and prospective cohort study met our inclusion criteria including data from a total of 4,797 participants. The pooled odds ratio (OR) for the metabolic syndrome comparing the highest and lowest category of ferritin levels was 1.20 (95% CI: 0.69, 1.71; I(2)=96%). The meta-analysis demonstrates that elevated ferritin levels are positive aassociated with metabolic syndrome. PMID- 26550260 TI - Effects of high mobility group box 1 and nuclear factor kappaB on neointimal hyperplasia after common carotid artery balloon injury. AB - This study is to investigate the effects of high mobility group box 1 (HMGB-1) and nuclear factor kappaB (NF-kappaB) on intimal hyperplasia after carotid artery balloon injury. A total of 28 male SD rats were subjected to balloon catheter injury at left side carotid artery and this side was considered as experimental group. The right side was taken as control group. Common carotid arteries were harvested at 6 h, 3 d, 7 d and 14 d after balloon injury. The intimal thickness and lumen area were analyzed by HE staining and computerized method. HMGB-1 expression was tested by RT-PCR and NF-kappaB was detected by EMSA. Among the 28 rats, 4 were excluded due to failed modeling or death and the other 24 rats were included for analysis. Carotid endarterectomy, intimal hyperplasia and restenosis were found after balloon injury. Intimal hyperplasia appeared on 3 d and was significant on 14 d after injury. The ratio of intima/media in the experimental group increased significantly compared with the control group (P < 0.05). HMGB-1 was scarcely expressed in control group. It increased 6 h and peaked on 14 d after injury, with significant difference compared with the control group (P < 0.01). Similarly to HMGB-1, NF-kappaB was rarely expressed in control group, and its level increased since 6 h and peaked on 14 d after injury. Intimal hyperplasia after carotid artery balloon injury was found in rat model and this might be induced by enhanced expression of HMGB-1 and NF-kappaB. PMID- 26550261 TI - Molecular mechanism of increased sensitivity of cisplatin to ovarian cancer by inhibition of microRNA-23a expression. AB - OBJECTIVE: The aim of this study is to investigate the sensitivity change and the preliminary mechanism of ovarian cancer cells on the resistant to chemotherapeutic drugs by inhibiting miR-23a expression. METHODS: The ovarian cancer cell lines A2780 was administrated with antagomir-23a and platinum, and then the cell proliferation inhibition rate was determined by MTT assay. The cell cycle distribution was detected by flow cytometric analysis. The apoptotic morphological changes were analyzed by Hoechst33258 staining. The glycoprotein P gp expression changes were detected by Western blot analysis. RESULTS: The cell proliferation inhibition rate increased significantly after the administration of miR-23a and platinum (P<0.01). The middle concentration of drug efficacy IC50 in experimental group decreased by 83.76% compared with that in control group, which was 17.89 MUmol/L vs 110.18 MUmol/L (P<0.01). The cell lines A2780 were arrested in G0/G1 phase and apoptosis rate kept increasing (P<0.05). The cell nuclei stained by Hoechst33258 were obviously enhanced and demonstrated apoptosis morphology, such as condense, pyknosis. Compared with control group, the levels of P-gp protein expression in experimental group decreased along with the increase of the cisplatin concentration (P<0.05). CONCLUSION: The inhibition of miR-23a expression could significantly increase the sensitivity of cisplatin towards tumor cells, and it was probably because the negative regulatory factors of miR-23a target genes was released, and as a result, the expression of P-gp protein was inhibited. PMID- 26550262 TI - The relationship between glycated hemoglobin and blood glucose levels of 75 and 100 gram oral glucose tolerance test during gestational diabetes diagnosis. AB - OBJECTIVE: The diagnosis of gestational diabetes mellitus (GDM) is an important issue in terms of prevention of maternal and fetal complications. In our study we aimed to evaluate the relation of HbA1c and blood glucose levels of 75 and 50-100 gram oral glucose tolerance test (OGTT) in pregnant patients who were screened for GDM. MATERIALS AND METHODS: The parameters of 913 pregnant women screened for GDM are evaluated retrospectively. The two steps screening with 50-100 gram OGTT were used in 576 patients. The remaining 337 patients were screened with 75 gram OGTT. RESULTS: The HbA1c levels of patients having high blood glucose (>=153 mg/dl) levels at 2(nd) hour in 75 gram OGTT were significantly higher than patients having normal blood glucose levels at 2(nd) hour of 75 gram OGTT (P=0.038). Correlation analyses showed no significant relation between any blood glucose level of 100 gram OGTT and HbA1c level. Whereas in 75 gram OGTT 1(st) and 2(nd) hour blood glucose levels were found to have a significant relation with A1c levels (P=0.001, P=0.001 respectively). CONCLUSION: HbA1c may be used as an important tool in the diagnosis of GDM. But due to the variation of HbA1c in pregnant women and there is not an absolute cut-off level for A1c, it may be more reliable to evaluate HbA1c level together with the blood glucose levels in OGTT. PMID- 26550263 TI - The role of mitochondrial tRNA mutations in lung cancer. AB - Alternations in mitochondrial genome resulting in mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondrial tRNA (mt tRNA) is known for its high frequencies of polymorphisms and mutations, however, the roles of these mutations and polymorphisms in lung cancer are among heated debates. To evaluate the possible roles of reported mt-tRNA mutations in lung cancer, we examine recent published paper concerning three mt-tRNA mutations with lung cancer: A7460G in tRNA(Ser (UCN)) gene, G5563A in tRNA(Trp) gene and A12172G in tRNA(His) gene. We perform the phylogenetic approach to investigate the deleterious roles of these mutations in lung cancer, moreover, we use bioinformatics tool to predict the secondary structure of mt-tRNAs with and without these mutations. In addition, through the application of pathogenicity scoring system, we find that only the A12172G mutation is regarded as a pathogenic mutation, whereas other mutations may act as neutral polymorphisms in human population. Thus, our study provides the novel insight into the molecular pathogenesis of mt-tRNA mutations in lung cancer. PMID- 26550265 TI - Detection of stably expressed piRNAs in human blood. AB - BACKGROUND: Circulating microRNAs are potential markers for disease detection. A novel class of small non-coding RNAs called Piwi-interacting RNAs (piRNAs) has been recently reported to participate in the epigenetic regulation of cancers and other diseases. This study aims to discover blood-based piRNAs which can be used as markers for disease detection and monitoring. MATERIALS AND METHODS: We selected five piRNAs for detection, namely, has-piR-651, has-piR-823, has-piR 36707, has-piR-36741 and has-piR-57125. Serum or plasma samples were used to isolate small RNAs, including the piRNAs. The extracted small RNAs were reverse transcribed in the presence of a poly-A polymerase with an oligo-dT adaptor, and quantitative real-time PCR (qRT-PCR) was applied to measure the levels of piRNAs. Room-temperature incubation and repetitive freeze-thaw cycles were performed to measure the stability of the piRNAs. RESULTS: Unlike the four other piRNAs, has piR-57125 was present in both the serum and plasma samples. Regardless of the serum or plasma samples, qRT-PCR analysis indicated that the Ct values showed no remarkable variation with prolonged incubation time (P > 0.05). We also detected the Ct values of the samples with repetitive freeze-thaw cycles and observed a similar trend (P > 0.05) among the samples with diverse freeze-thaw cycles. CONCLUSION: This study is the first to report that piRNAs are stably expressed in human serum or plasma samples. Therefore, piRNAs can serve as valuable blood based biomarkers for disease detection and monitoring. PMID- 26550264 TI - Decorin protects human hepatoma HepG2 cells against oxygen-glucose deprivation via modulating autophagy. AB - This study is to investigate the effects of decorin (DCN) on human hepatoma HepG2 cells under oxygen-glucose deprivation (OGD) condition. HepG2 cells were cultured under OGD condition. CCK-8 assay was used to assess the cell survival, and flow cytometry was performed to detect the apoptosis. Protein expression levels were detected with Western blot analysis. Transfection was performed with liposome, and cells were screened with G418. The cell survival rates were significantly decreased in the OGD groups. When treated with autophagy inhibitor 3-MA, the survival rates were further declined in these cells. Moreover, flow cytometry indicated that apoptosis occurred in the HepG2 cells under OGD condition, and the apoptosis rates were significantly increased by the 3-MA treatment. Western blot analysis showed that, the expression levels of DCN were significantly elevated in OGD-preconditioned HepG2 cells. Meanwhile, the expression level of Beclin1 and the LC3BI/LC3BII ratio were significantly increased, while the expression level of P62 was significantly decreased, in HepG2 cells under OGD condition. Over expression of DCN significantly increased the expression level of Beclin1 and the LC3BI/LC3BII ratio, while no significant changes were observed in the P62 expression level, in HepG2 cells. Under the OGD condition, the apoptosis rate was also significantly decreased in DCN-transfected HepG2 cells. DCN protects HepG2 cells against OGD-induced injury, via regulating autophagy. These results might contribute to a better understanding of the roles of DCN and autophagy in hepatocellular carcinoma, and the potential treatment for the disease. PMID- 26550266 TI - Prediction of liver injury using the BP-ANN model with metabolic parameters in overweight and obese Chinese subjects. AB - Nonalcoholic fatty liver disease (NAFLD) is often associated with dyslipidemia. Metabolic disequilibrium, resulting from being overweight and obesity, increases risk to cardiovascular system and chronic liver disease. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) are standard clinical markers for liver injury. In this study, we examined association of body mass index (BMI) and metabolic markers with serum ALT, AST and GGT activity in an overweight and obese Chinese population. A total of 421 overweight and obese Chinese adults (211 males and 210 females) from The First Affiliated Hospital of Wenzhou Medical University were recruited in this study in 2014. All participants underwent anthropometric measures and phlebotomy after an overnight fast. Elevated ALT, AST and GGT levels were found in 17%, 5% and 24%, respectively. There were significant correlations between ALT and BMI, plasma triglycerides (TG), cholesterol, HDL and glucose, and between AST and plasma TG and cholesterol. GGT also correlated with plasma TG, cholesterol and glucose. The levels of ALT, AST and GGT could be predicted by BMI, plasma TG, cholesterol, HDL and glucose using the back propagation artificial neural network model (BP-ANN). These data suggest that abnormal metabolic markers could be used to monitor liver function to determine whether liver damage has occurred in overweight and obese individuals. This approach has clinical utility with respect to early scanning of liver injury or NAFLD based on routinely available metabolic data in overweight and obese population. PMID- 26550267 TI - The lower expression of gonadotropin-releasing hormone receptor associated with poor prognosis in gastric cancer. AB - AIMS: Expression of gonadotropin-releasing hormone receptor (GnRHR) has been demonstrated in a number of malignancies. The aim is to investigate the expression of GnRHR and prognosis in gastric cancer. METHODS AND MATERIALS: GnRHR mRNA was examined in tumor and non-tumor tissues from 48 gastric cancer patients by Real-time PCR. The GnRHR protein expression was performed by immunohistochemical analysis. RESULTS: The expression of GnRHR mRNA was higher (mean +/- SD, -10.06 +/- 1.28) in gastric tumor tissues than matched non-tumor tissues (mean +/- SD, -12.43 +/- 1.33). GnRHR mRNA expression was associated with lymph node metastasis, distant metastasis, and TNM stage. We found the decreased expression of GnRHR mRNA were significantly correlated with poor overall survival (P = 0.003). Immunocytochemical staining of GnRHR in tumor tissues showed mainly weak staining (43.48%, 10/23) and moderate staining (21.74%, 5/23) in high GnRHR mRNA patients, and mainly negative staining in low GnRHR mRNA patients. And the staining of GnRHR was not detection in tumor tissues for more than half of gastric patients (52.08%, 25/48). These results implied that the loss of GnRHR protein could be a main event in gastric cancer. CONCLUSION: The GnRHR expression is very low in gastric cancer, and the loss of GnRHR expression could be a poor prognostic factor, which implied that GnRHR could play an important role in the development of gastric cancer. PMID- 26550268 TI - RAGE/NF-kappaB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model. AB - Lipopolysaccharide (LPS) is known to induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Accumulating data suggest the crucial role of RAGE in the pathogenesis of ALI/ARDS. However, the mechanism by which RAGE mediates inflammatory lung injury in the neonates remains elusive. In this study we established LPS-induced ALI model in neonate rats, and investigated the role of RAGE/NF-kappaB signaling in mediating ALI. We found that RAGE antibody or bortezomib reduced LPS-induced histopathological abnormalities in the lung and lung damage score. RAGE antibody or bortezomib also reduced TNF-alpha level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-kappaB expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-kappaB signaling. Interference with RAGE/NF-kappaB signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS. PMID- 26550269 TI - Fasudil alleviates traumatic optic neuropathy by inhibiting Rho signaling pathway. AB - OBJECTIVES: The present study is to investigate the pathological changes in rabbits with traumatic optic neuropathy (TON), as well as the effect of fasudil on the lesions. METHODS: A total of 144 New Zealand rabbits were successfully established as TON models. Twelve hours after surgery, the rabbits in control, dexamethasone, and fasudil groups were administrated with saline, dexamethasone, and fasudil via ear veins, respectively. Then, retinas of the rabbits were obtained at 72 h and on days 7, 14 and 21 after surgery. The pathological changes in retina and optic nerves were observed by hematoxylin and eosin staining and transmission electron microscopy. The expression levels of Rho-associated genes were measured using quantitative real-time polymerase chain reaction. RESULTS: In control group, the axons were swelling, and mitochondria showed vacuolation after optic nerve crush. Mitochondria were swelled slightly in dexamethasone group. By contrast, nerves in fasudil group were repaired. Retinal ganglion cells in control group were reduced significantly due to optic nerve crush. The loss of retinal ganglion cells was alleviated in fasudil group. Quantitative real-time polymerase chain reaction showed that the expression of Rho-associated genes were down-regulated. CONCLUSIONS: The present study demonstrates that fasudil inhibits the apoptosis of retinal ganglion cells and ameliorates damages of optic nerves in traumatic optic neuropathy. PMID- 26550270 TI - Morphology of mouse sinoatrial node and its expression of NF-160 and HCN4. AB - OBJECTIVE: To explore the morphology and cell component of the sinoatrial node in adult mice and to observe the expressions of neurofilament protein (NF-160) and hyperpolarization-activated cyclic nucleotide regulation of cation channel 4 (HCN4) in sinus node cells. METHODS: The right and left atria were collected from 10 adult mice. After paraffin embedding and serial section, these sections underwent Masson trichrome staining and NF-160 immunohistochemical staining, respectively, followed by observation under a light microscope. The right and left atria from another 5 mice were used for immunofluorescence staining using NF 160 and HCN4 antibodies, respectively, followed by observation under a confocal microscope. RESULTS: The mouse sinoatrial node was close to the superior vena cava and below the epicardium. The shape of the mouse sinoatrial node was ovoid or irregular in the horizontal sections. We clearly saw a sinus node artery passing through the sinoatrial node, so the artery can be used as a location marker of the sinoatrial node. Immunofluorescence displayed the expression of NF 160 and HCN4 in both pacemaker cells and transitional cells of the sinoatrial node. Finally, sinoatrial node migrated along with Purkinje fibers of the right atrium. CONCLUSION: The position of mouse sinoatrial node is more stable. The distal end of sinoatrial node extends to the right subendocardial layer and migrates with Purkinje fibers. In mouse sinoatrial node, both pacemaker cells and transitional cells are regularly distributed, and all have HCN4 and NF-160 expression. PMID- 26550271 TI - Expression of FOXC2 in renal cell carcinoma and its relationship to clinical pathological features. AB - OBJECTIVE: This study aimed to investigate expression level of FOXC2 and its relationship to clinical pathological features of renal cell carcinoma (RCC). METHODS: The expression levels of FOXC2 in RCC tissues and normal renal tissues (62 samples, respectively) were detected by immunohistochemistry and PCR Array. Statistics analyses were done with SPSS to compare the differences between RCC tissues and normal renal tissue, and to explore the relationship between the expression level of FOXC2 and the clinical pathological features of RCC. RESULTS: Expression level of FOXC2 in RCC tissues was significantly higher than in normal renal tissues, and other related cancer genes also highly expressed in RCC tissues. FOXC2 expression was positively associated with clinical stage and pathological grade (P < 0.05), but not significantly related to the gender and age (P > 0.05). CONCLUSION: The expression of FOXC2 in renal cell carcinoma was significantly higher than that in normal renal tissues. It is suggested that FOXC2 might play a crucial role in the occurrence and development of RCC and could be an important prognostic indicator for clinical therapy. PMID- 26550272 TI - Finite element analysis of the stability of combined plate internal fixation in posterior wall fractures of acetabulum. AB - OBJECTIVE: This study aims to explore the mechanical stability of combined plate internal fixation in posterior wall fractures of the acetabulum. METHODS: The fracture and internal fixation models were established in this study and they were divided into four kinds of internal fixation models, finite element analysis was performed. The four groups were 2 mini-plates and 1 reconstruction plate fixation (A), Reconstruction plate internal fixation group (B), 2 screws internal fixation group (C) and mini-plates internal fixation group (D). The displacement of each node was measured and evaluated. RESULTS: There was no distortion in the geometric shape of the finite element model. The results of stress showed that it was less in the anterior pelvic ring and distributed uniform in labrum acetabulare; the stress was bigger in the upper and middle of sacroiliac joint and sciatic notch in sitting position. CONCLUSIONS: Combined plate internal fixation for posterior wall fractures of acetabular were stable and reliable, it is better than the other three methods. PMID- 26550273 TI - Lower serum bilirubin concentration in patients with migraine. AB - BACKGROUND: Bilirubin has been seen as a toxic waste product since it is product of heme metabolism. It's the latest in a series of studies showed that the concentration of serum bilirubin is associated with various diseases such as multiple sclerosis, hypertension and cardiovascular diseases (CVD). However, no study to investigate the association between serum bilirubin and migraine, thus, our aim is to investigate the association between serum bilirubin and migraine. METHODS: Serum samples were collected from 120 patients with migraine and 128 healthy individuals, serum total bilirubin (Tbil), serum direct bilirubin (Dbil) and serum indirect bilirubin (Ibil) concentration were measured to this study. RESULTS: Tbil, Dbil and Ibil concentration were significantly lower in patients with migraine than healthy controls. Tbil, Dbil and Ibil concentration also were lower in patients with migraine compared with healthy controls when serum bilirubin concentration further was grouped by gender. CONCLUSIONS: We found evidence that lower serum bilirubin in patients with migraine, serum bilirubin may be useful markers to estimate neurogenic inflammation in patients with migraine. PMID- 26550274 TI - Surgical treatment for a paraplegic patient induced by congenital factor X deficiency. AB - Congenital factor X (FX) deficiency is a rare disease which usually leads to coagulation disorders. We reported a case of paraplegic patient induced by traumatic spinal epidural hematoma which was associated with congenital FX deficiency. The treatments of this patient included elevating FX activity (FX: C) by adding fresh-frozen plasma (FFP) or prothrombin complex concentration (PCC) to improve his coagulation function, and doing operation to remove his spinal hematoma. Symptoms started to resolve after operation. Besides, we found one of his elder brother had the same disease as the patient himself via family follow up. They can survive because their FX: C are relatively high enough to keep them away from fatal bleeding. PMID- 26550275 TI - Regional tissue immune responses after sciatic nerve injury in rats. AB - Inflammatory cells play a critical role during nerve regeneration following peripheral nerve injury. In this study, we investigated immune responses in rat sciatic nerve after injury. Wistar rats were randomly divided into the sciatic nerve injury (model) group and control group. The right sciatic nerve of rats in the model group was transected and sutured end-to-end. Our results showed that rats in the model group functionally recovered following sciatic nerve injury. We detected inflammatory cell infiltration in the remaining sciatic nerves following injury. In addition, expression of interferon-gamma (INF-gamma), interleukin-10 (IL-10), and the INF-gamma/IL-10 ratio was significantly elevated one week following nerve injury, but gradually decreased thereafter. Our findings demonstrate that immune responses and inflammatory cell activation are involved during recovery from sciatic nerve injury. PMID- 26550276 TI - MDM2 T309G polymorphism and esophageal cancer risk: a meta-analysis. AB - Murine double minute 2 (MDM2) has suggested to play an important role in esophageal cancer. The association between MDM2 T309G polymorphism and esophageal cancer risk was inconclusive. To clarify the possible association, we conducted a meta-analysis. We searched in the PubMed, Embase, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 6 studies with 4909 cases and controls were included based on the search criteria. The MDM2 T309G polymorphism was associated with a significantly decreased risk of esophageal cancer (OR=0.88; 95% CI, 0.81-0.96; I(2)=22%). When stratified by type of race, a significantly decreased esophageal cancer risk were observed in Asians (OR=0.85; 95% CI, 0.78-0.93; I(2)=0%). In conclusion, this meta-analysis suggested that MDM2 T309G polymorphism was associated with a significantly decreased risk of esophageal cancer. PMID- 26550277 TI - Three different methods for treating multiple enchondromatosis in one hand. AB - Ollier's disease remains comparatively rare, and is a non-hereditary cartilage dysplasia of bone. It is usually associated with problems such as deformity and fracture. Three different methods were used in a one-hand of 15-year-old boy reporting his pain in the left hand and swellings. After the curettage of tumor, regarding as the differences of all parts of the bone structure reconstruction in the patient's hand, we chose three following methods for this boy, i.e. fixed by the locking plate with calcium phosphate cement, filled with allograft bone, curetted the tumor without any bone graft. After the surgery, the patient was able to perform full motion of the operated hand. No evidence of recurrence was noted four years after surgery. To choose the different ways with bone grafts or not that relies on the patients' conditions for bone structure reconstruction. However, patients with large osseous defects or pathological fracture, we demand full bone graft and reliable internal fixation. After surgery, early exercises can reach a desirable result and functional recovery. PMID- 26550278 TI - The use of latex foley catheter in repair of hypospadias the most common seen congenital penile anomaly. AB - OBJECTIVE: Hypospadias is the most common congenital penile anomaly occurring in 1/300 live births. Various surgery techniques are used in repair of hypospadias. Infant and children with hypospadias are usually admitted to emergency services by worried their parents for the first time. TIP urethroplasty is widely used in the repair of hypospadias, but the use of urethral catheters is still a matter for discussion. Herein, we described our experiences with the use of an unsutured latex foley catheter placed in the glans for 24 to 48 hours. METHODS: A retrospective chart review was performed on 38 patients who underwent Tubularized incised plate (TIP) hypospadias repair from 2009 to 2011. Of these, 35 patients who had two-way latex Foley catheters placed for 24 h to 48 hands were followed for at least 12 month. RESULTS: Excellent cosmetic results were obtained in all patients. Urinary tract infection developed in two patients (5.7%). one patient (2.8%) who had mild urethral repair breakdown was repaired in the office environment. CONCLUSION: We observed very low complication rates in application of a two-way latex Foley catheter in hypospadias surgery and found that this method can be used safely. Moreover, the catheter can be used for traction purposes during the procedure. At the end of the 24 to 48 h period, removal of the two-way latex urethral catheter with balloon does not harm the urethral repair. To reach a definite conclusion, larger studies are needed. PMID- 26550279 TI - Gait modification strategies of trunk over left stance phase in patients with right anterior cruciate ligament deficiency. AB - PURPOSE: To investigate the gait modification strategies of trunk over left stance phase in patients with right anterior cruciate ligament deficiency (ACL D). METHODS: Thirty-six patients with right ACL-D and thirty-six health subjects (control) were recruited to undergo a 3-dimensional (3D) gait analysis. Coordinate data from 26 reflective markers positioned on the body surface of participants were recorded with a 3D optical video motion capture system, as they walked on the ground, ascended and descended a custom-built staircase. Angle changes in the 3-planes under different walking conditions were analyzed. RESULTS: There were statistically significant differences between the two groups in the trunk at the transverse plane angle in most measurements. With the walk pattern of stair descent, the trunk at all 3-plane angles, at the maximum value of the left knee sagittal/coronal/transverse plane moment, was significantly different between the two groups (P <= 0.03). CONCLUSIONS: Our findings suggested that special gait modification of trunk is apparent over stance of left (healthy) side in patients with right ACL-D. The results of this study may supply more insight with respect to improving the diagnosis and rehabilitation of ACL-D. This information may also be helpful for a better use of walk and stair tasks as part of a rehabilitation program and provide a safe guideline for the patients. PMID- 26550280 TI - The effect of prediagnostic aspirin use on the prognosis of stage III colorectal cancer. AB - BACKGROUND: Many studies have suggested that the regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, has a protective effect and survival benefit on colorectal cancer (CRC). However, recent data suggest that CRCs have different responses to NSAIDs depending on the timing of NSAID initiation, duration of NSAID use, and molecular characteristics of the tumor. The aim of this study was to evaluate the effect of long-term prediagnostic aspirin use on the prognosis of stage III CRC. METHODS: From 2007 to 2009, patients who were diagnosed with stage III CRC were recruited, and their medical records were retrospectively analyzed. Patients were divided into prediagnostic aspirin users (who used aspirin for more than three months continuously before CRC diagnosis) and non-users (who did not use of aspirin and NSAIDs). The two groups were compared in terms of recurrence, cancer-specific mortality, disease free survival (DFS), and cancer-specific survival. In an experimental study, three CRC cell lines (Caco2, SW480, and DLD-1) were pretreated with aspirin (1 mM) for four days or 28 days to make aspirin-resistant cells, treated with 5 fluorouracil (5-FU; 2 uM), and apoptosis was measured with flow cytometry using Annexin-V and propidium iodide double staining. RESULTS: Compared with the aspirin non-users (N=565), the prediagnostic aspirin users (N=121) were not different in terms of baseline characteristics including tumor characteristics, except for comorbidities and diabetes medication and statin use, which were higher in the prediagnostic aspirin users. Recurrence and cancer-specific mortality in stage III CRC were significantly higher in prediagnostic aspirin users than non-users (46.7% vs. 32.3%, P=0.003 and 32.2% vs. 19.8%, P=0.003, respectively). Survival analysis using Cox proportional hazards modeling demonstrated that DFS was significantly worse in prediagnostic aspirin users than non-users (HR, 1.525 (1.018-2.286); P=0.041). In cell line experiments, long-term aspirin pretreatment induced an increase in 5-FU-induced apoptosis in SW480 cells compared with control treatment without aspirin pretreatment. However, Caco2 cells showed a significant decrease of apoptosis in the same experiments and no change in DLD1 cells. CONCLUSION: Prediagnostic long-term aspirin use in stage III CRC could be a negative prognostic factor depending on the characteristics of the CRC. PMID- 26550281 TI - Genetic effects of common polymorphisms in estrogen receptor alpha gene on osteoarthritis: a meta-analysis. AB - OBJECTIVE: The estrogen receptor alpha (ESR1) gene has been implicated in the etiology of osteoarthritis (OA). However, the results are conflicting. We assessed the association of three common ESR1 polymorphisms, rs2234693, rs9340799 and rs2228480, with OA in this meta-analysis. METHODS: A comprehensive search was performed to identify related studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed or random effects model. RESULTS: 15 studies (7036 cases and 9669 controls) for rs2234693 polymorphism, 14 studies (3904 cases and 6991 controls) for rs9340799 and 3 studies (331 cases and 619 controls) for rs2228480 polymorphism were identified. The final results indicated that the G allele in ESR1 rs9340799 was associated with decreased OA risk (GG+GA vs. AA: OR=0.878, 95% CI=0.792-0.972, P=0.012; G vs. A: OR=0.902, 95% CI=0.836 0.975, P=0.009). The A allele in rs2228480 might be associated with increased OA risk. But no significant association of rs2234693 polymorphism with OA susceptibility was observed. CONCLUSIONS: This meta-analysis indicates rs9340799 and rs2228480 rather than rs2234693 polymorphisms are associated with the incidence of OA. Some stable associations should be further confirmed in future. PMID- 26550282 TI - A useful surgical strategy for proximal tibial fractures (AO/OTA type 41-C) with diaphyseal involvement. AB - Relatively few studies have addressed surgical strategy for complex proximal tibial fractures by now. The purpose of this study was to assess the results of a single lateral locking plate using minimally invasive plate osteosynthesis (MIPO) for proximal tibia fractures (AO/OTA type 41-C) with diaphyseal involvement. From Jun 2009 to Jun 2014, 20 patients (fifteen women and five men, mean age 35.8 years) were managed for proximal tibial fractures which extend into the diaphyseal region of the bone, including three 41-C1, eleven 41-C2, and six 41 C3. Twelve patients were open fractures. A single lateral locking plate characterized by percutaneous technology was used with or without additional lag screws. Mobilization was started immediately after the procedure, and non-weight bearing was maintained for at least 6 weeks, then progressively weight bearing depends on both clinical and x-ray findings. Primary union was achieved by 16 of the 20 study subjects. Early bone grafting was performed in 4 cases with a massive initial bone defect and staged bone grafting was used in one to treat nonunion. The mean articular step off was 1.0 mm (range, 0-3 mm). No patient had misalignment greater than 10 degrees . Acceptable range of knee motion of >=120 degrees was achieved in sixteen, and the mean knee Hass score was 87.4 at final follow-up visits. The complications included superficial infection in one patient. In conclusion, the surgical strategy can provide favorable results in the treatment of proximal tibial fractures (AO/OTA type 41-C) with diaphyseal involvement. PMID- 26550283 TI - Predictive accuracy comparison of MELD and Child-Turcotte-Pugh scores for survival in patients underwent TIPS placement: a systematic meta-analytic review. AB - BACKGROUND: Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores have been used commonly to predict the survival in the patients with liver diseases underwent transjugular intrahepatic portosystemic shunt (TIPS). However, a debate has continued for years whether CTP could be replaced by MELD score. We performed a systematic meta-analytic review to compare the prediction capability of both scores in survival among patients with TIPS. METHODS: Retrospective cohort studies among patients with TIPS were published as of May 2013 were identified by systematically searching four electronic literature database, such as Ovid Medline, PubMed, EMBASE, and ISI Web of Science. The difference of standardized mean difference (SMD) of c-statistics for the predictive accuracy of 1-, 3-, 6-, and 12-month survival for both MELD and CP scores, defined as effect size (ES), was calculated for each individual study and then pooled across studies using standard meta-analyses with a random effects model. Publication bias was evaluated using funnel plots and Kendall's rank correlation tests. RESULTS: 174 researches articles or conference abstracts were searched and reviewed using the combination of relevant terms in the articles. Finally, 11 articles were defined as eligible studies to evaluate simultaneously the predictive accuracy of MELD and CTP scores. In the meta-analyses, MELD score was superior to CP score in predicting 3-month survival after TIPS (mean ES, 0.63; 95% confidence interval [CI], 0.13-1.14; P=0.01), but the predictive capability in 1-month, 6-month, and 12-month survival was not significant (1 month: mean ES, 0.79; 95% CI, -0.24-1.83; P=0.13; 6-month: mean ES, 0.46; 95% CI, -2.46-3.37; P=0.76; 12-month: mean ES, 0.36; 95% CI, -0.25-0.96; P=0.25). CONCLUSIONS: No enough evidence are confirmed so far that MELD score is better than CTP score to assess the overall prognosis after TIPS, especially long-term predictions, but 3-month predictive capability of MELD score significantly outperform CTP score. PMID- 26550284 TI - The clinical effect of percutaneous kyphoplasty for the treatment of multiple osteoporotic vertebral compression fractures and the prevention of new vertebral fractures. AB - This study aimed to investigate the clinical effect of percutaneous kyphoplasty and the precautions against adjacent vertebral refractures in the treatment of multiple osteoporotic vertebral compression fractures. 54 cases (128 vertebrae) with multiple osteoporotic vertebral compression fractures from July 2007 to December 2013 treated with percutaneous kyphoplasty were retrospectively reviewed. 36 cases of them suffered from bi-segment vertebral fractures, 16 cases with tri-segment vertebral fractures and 2 cases with quadri-segment vertebral fractures. The operative effect was evaluated by visual analogue scale (VAS) score and oswestry disability index (ODI) score. Then the reasons for adjacent vertebral refractures were analyzed and the precautions were proposed. 54 cases (128 vertebrae) were admitted with percutaneous kyphoplasty successfully. No pulmonary embolism, spinal cord injury and other serious complications were found. The follow-up took 3-33 months with the average of 12 months. There was significant difference of VAS scores and ODI scores between pre-operation and post-operation (P<0.05). Bone cement leakage occurred in 23 vertebrae, and the incidence rate was 18.0%. 8 cases sustained adjacent vertebral refractures including 3 cases in the contiguous vertebral bodies and 5 cases in the interval vertebral bodies, and the incidence rate was 14.8%. 5 cases gained fracture healing after additional percutaneous kyphoplasty procedures while the other 3 cases were healed basically after conservative treatment for three months. In conclusion, percutaneous kyphoplasty is safe and effective to treat multiple osteoporotic vertebral compression fractures. However, the risk of new adjacent vertebral fractures in the multiple osteoporotic vertebral compression fractures is higher than that in the single osteoporotic vertebral compression fracture. Timely and proper treatment can reduce refractures. PMID- 26550285 TI - The clinical characteristic and risk of capsule incomplete and retention in Crohn's disease. AB - OBJECTIVE: To evaluate capsule endoscopy in terms of incomplete examinations and capsule retentions, to describe the characteristic of these events and to find risk factors for these events. METHODS: This retrospective and consecutive case control study includes data of 204 capsule enteroscopy examinations in patients with Crohn's Disease, performed at the first hospital affiliated to zhejiang university medical school from June 2003 to April 2014. RESULTS: The frequency of complete examinations was 56.9%. Male gender (OR=2.48, P=0.026), abdominal pain (OR=2.88, P=0.002), melena/bloody stools/OB+ (OR=3.34, P=0.009) were risk factors for an incomplete examination. Capsule retention occurred in 8.33% (n=17). The ratio of male and female was 12:5. While the average age of these patients was 42.2+/-16.2, and the average course of disease was 52.5+/-46.6 months. Of the seventeen cases of retained capsules, four patients chose to undergo surgery to remove the capsule for occurring symptoms of intestinal obstruction, spontaneous passage occurred in twelve patients after medical treatment, and one patient still have the capsule retained after 16 months of expectation. The longest capsule retained time in patients was four years. Risk factors for capsule retention was abdominal distention (OR=8.45, P=0.006). CONCLUSIONS: The majority of capsule endoscopy retention develops into spontaneous passage after medical treatment. Therefore capsule endoscopy is considered a safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in patients with known Crohn's disease. PMID- 26550287 TI - Two types of isolated epileptic nystagmus: case report. AB - Epileptic nystagmus (EN) is a quick, repetitive jerky movement of the eyeball caused by seizure activity, unaccompanied by other ictal phenomena rare. Here, we described two cases, one characterized by binocular and the other by monocular isolated epileptic nystagmus (IEN), and we identified the characteristics of the etiology, clinical manifestations, electroencephalogram, imaging, treatment and prognosis in epileptic nystagmus through reviewing literature. We found IEN occurs more frequently in children than in adults. Etiological factors included trauma, cerebral vascular disease, tumor, and anoxia. The frequency of IEN was high, which varied from several to hundreds of times per day, and the duration of it was usually less than 1 minute. EN and its subtypes, such as epileptic monocular nystagmus, vertical epileptic nystagmus, epileptic skew deviation, periodic alternating nystagmus, and partial oculo-clonic status, are rare. The fast phase of the nystagmus was contralateral to the epileptogenic zone in most cases. Periodic lateralized epileptiform discharges (PLEDs) is a distinct EEG pattern in EN. Our findings suggested that the occipital lobe may plays a key role in the origin of EN. PMID- 26550286 TI - Association between IL-6 and related risk factors of metabolic syndrome and cardiovascular disease in young rats. AB - OBJECTIVE: Metabolic syndrome (MS) is conceived as the pathogenic basis of an increased cardiovascular burden. We investigate the correlation between interleukin-6 (IL-6) and the risk factors of MS and cardiovascular disease (CVD) in diet-induced model of MS and determined whether IL-6 was associated with the prevalence of MS and cardiovascular disease. METHODS: A total of 40 Spague-Dawley (SD) rats were randomly divided into high-fat and high salt (FSC) group, high-fat (FC) group and normal control (NC) group. After feeding for 7 weeks, fasting blood glucose (FBG) and fasting insulin (FIN) were measured at the 60 min, 120 min and 180 min after the glucose administration. Blood pressure, body weight, height, waist circumference (WC), liver weight, visceral fat weight as well as blood lipid profile were determined at the end of 7-week. Furthermore, IL-6 levels from adipose tissues were analyzed using ELISA, and the correlation between IL-6 and the risk factors of MS and cardiovascular disease was investigated. RESULTS: After treatment with different diets, significant difference was noted in the WC, body mass index (BMI), visceral fat weight and liver weight of FSC group compared with those of NC group (P<0.05). The levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triacylglycerol (TG) and low density lipoprotein (LDL) were markedly elevated in FSC group compared with those in NC group, while the level of high density lipoprotein (HDL) was remarkable lower in FSC group (P<0.05). After glucose administration, the concentrations of blood glucose and insulin were significant higher in FSC group than those in NC group at different time points (P<0.05). Moreover, high-fat and high salt diet brought about significant elevation of IL-6 compared with that with normal or high-fat diet in SD rats. Furthermore, IL-6 was significantly associated with FIN, HOMA-IR, LDL, TC, TG, HDL, visceral fat mass and body weight in FSC group, while IL-6 was markedly correlated with TC, LDL, TG, visceral fat mass and body weight (P<0.05). CONCLUSION: A characteristic rat model of MS may be induced by the high-fat and high-salt diet. IL-6 may be considered as an early and representative marker in the pathogenesis of MS and related cardiovascular burden. PMID- 26550288 TI - Guidance value of intracranial venous circulation evaluation to parasagittal meningioma operation. AB - OBJECTIVE: This study is to investigate the value of intracranial venous circulation evaluation in guiding the surgery for parasagittal meningioma. METHODS: A total of 44 parasagittal meningioma (PSM) patients received 3D CE-MRV scanning. The obtained images were reconstructed by virtual reality (VR) technology. Venous collateral circulation was evaluated. Postoperative follow-up was carried out. RESULTS: Among 44 PSM patients, 41 cases were with resection of Simpson grade I/II (93.18%) and 6 cases were with permanent neurological dysfunction (13.64%). Venous sinus thrombosis occurred in the remaining 3 patients (6.82%), with 2 cases cured and 1 case died. The mortality rate was 2.27%. Recurrence occurred in one case (2.27%) after discharge. In 9 cases, tumor adjacent SSS was transected and the poor prognosis rate was 33.33%. SSS was opened in 3 cases and after removal of the tumor the broken end was sutured directly. The poor prognosis occurred in one case (33.33%). Electrocoagulation was carried out to the SSS wall in 32 cases without opening venous sinus and 2 cases were with poor prognosis (6.25%). The three different venous sinus treatment methods had no significantly difference on the prognosis of patients (P > 0.05). CONCLUSIONS: Preoperative evaluation of intracranial venous circulation with VR technology and 3D CE-MRV may help making individual surgical plans, reduce venous injury and improve the prognosis of PSM patients. PMID- 26550289 TI - Case-matched analysis of combined thoracoscopic-laparoscopic versus open esophagectomy for esophageal squamous cell carcinoma. AB - The aim of this study is to evaluate surgical results and long-term survival of combined thoracoscopic-laparoscopic esophagectomy (TLE) performed for esophageal squamous cell carcinoma. Data of 59 patients with esophageal squamous cell carcinoma, undergoing TLE from January 2007 to January 2015, were compared to a control group of 59 patients who underwent open esophagectomy (OE) during the same period. The two groups were matched in terms of age, sex, American Society of Anesthesiology (ASA) score and clinical TNM stage. Laparoscopic approach resulted in longer operating time (P=0.003) and lower blood loss (P=0.000). There was no difference in perioperative morbidity and mortality rate; TLE approach was associated with a shorter hospital stay (P=0.000). After a mean follow up of 38 months, 5-year disease free survival and 5-year overall survival were 38% and 50% for TLE group, and 36% and 45% for OE group (P>0.05). TLE for esophageal squamous cell carcinoma is feasible and safe in selected patients and can result in good surgical results, with similar outcomes in terms of long-term outcomes. PMID- 26550290 TI - Baseline quantitative hepatitis B core antibody could strongly predict survival for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. AB - The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) in HCC patients after transarterial chemoembolization (TACE) is rare. The aim of this study was to determine the prognostic significance of anti-HBc in HCC patients after TACE. A total of 66 HCC patients with complete data and treated with TACE in Nanfang Hospital, Southern Medical University were retrospectively analyzed. Univariate analyses were performed for 20 pretreatment variables and those with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. Among the 66 HCC patients, the 0.5-, 1-, and 2-year overall survival rates were 92.42%, 50.00%, and 21.21%, respectively. We defined 11.88 S/CO, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict the OS rate in HCC patients after TACE. Univariate and multivariate analyses revealed that baseline anti-HBc level, AFP level and vascular invasion were the only three independent significant prognostic factors of overall survival (P = 0.001, 0.020 and 0.010, respectively). We demonstrated that baseline anti-HBc level, combining AFP level and vascular invasion, might be a novel biomarker for predicting the survival of HCC patients after TACE. PMID- 26550291 TI - Correlation of TLR2 and TLR4 expressions in peripheral blood mononuclear cells to Th1- and Th2-type immune responses in children with henoch-schonlein purpura. AB - We discussed the correlation of TLR2 (Toll-like receptor) and TLR4 expressions in peripheral blood mononuclear cells (PBMCs) to Th1- and Th2-type immune responses in children with Henoch-Schonlein Purpura (HSP). The role of TLR2 and TLR4 in the pathogenesis of HSP was analyzed. Sixty-four HSP children treated at our hospital from October 2011 to November 2012 were enrolled and divided into NHSPN group (complicated by renal impairment, 36 cases) and HSPN group (not complicated by renal impairment, 28 cases). In the meantime, 30 normal children receiving physical examination at our hospital were recruited as controls. Peripheral blood T cell subgroups and TLR2 and TLR4 expressions in PBMCs were detected by using flow cytometry; relative expression levels of TLR2 and TLR4 mRNA in PBMCs by real time quantitative fluorescence PCR, and plasma levels of IFN-gamma, IL-4 and IL-6 by ELISA method. Relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in children with HSP were significantly higher than those of the controls (P<0.01). The relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in HSPN group were obviously higher than those in NHSPN group (P<0.05; P<0.01; P<0.01; P<0.01); CD3(+) T cells and CD3(+)CD4(+) T cells in HSP group were significantly decreased, while CD3(+)CD8(+) T cells and CD3(+)HLADR(+) T activated cells were considerably increased (P<0.01); The plasma levels of IL-4 and IL-6 in HSP group were significantly higher than those of the normal controls (P<0.01, P<0.01); IFN gamma level in the former was much lower than in the control group (P<0.05); IFN gamma/IL-4 ratio in the former was also lower than that in the control (P<0.01); TLR2 and TLR4 expressions in HSP group showed significantly positive correlation with the plasma levels of IL-4 and IL-6 (P<0.01, P<0.05; P<0.01, P<0.01) and significantly negative correlation with IFN-gamma/IL-4 ratio (P<0.01; P<0.01). TLR2 and TLR4 activation may be involved in the pathogenesis of HSP. TLR2 and TLR4 overactivation may induce HSP-related renal impairment; Children with HSP showed T-cell disorders and Th1/Th2 imbalance. Activated TLR2 and TLR4 possibly mediate the pathogenesis of HSP by upregulating Th2-type immune responses. PMID- 26550292 TI - Effect of disulfiram on ketamine-induced cardiotoxicity in rats. AB - It is known that ketamine increases the production of catecholamines, causing oxidative damage to the heart. Suppression of the production of catecholamines by disulfiram, a drug with antioxidant properties, indicates that disulfiram may decrease ketamine-induced cardiotoxicity. The objective of the present study was to investigate the effect of disulfiram on ketamine-induced cardiotoxicity in rats. Disulfiram was administered by oral gavage in doses of 25 mg/kg to rats in the DK-25 group and 50 mg/kg to rats in the DK-50 group. Distilled water was applied in the ketamine control (KC) and healthy (HG) rat groups. At one hour after drug administration and subsequently at ten-minute intervals, a 60 mg/kg dose of ketamine was intraperitoneally injected in the rats in all groups other than HG, and anesthesia was maintained for three hours. Disulfiram prevented both increase in the levels of parameters indicating oxidative and myocardial damage and decrease of antioxidant levels in the heart tissue with ketamine in a dose dependent manner. Disulfiram better prevented occurrence of cardiotoxicity with ketamine in the 50 mg/kg dose than in the 25 mg/kg dose. It is concluded that disulfiram may usefully be applied in clinical practice in the prevention of cardiotoxicity as observed during anesthesia with ketamine. PMID- 26550293 TI - Effects of vitamin D on kidney histology and trpv1 channels in doxorubicin induced nephropathy. AB - Doxorubicin (DXR) is an antineoplastic agent of the anthracycline group, and may show nephrotoxic effects in animal models and humans. We investigated changes in kidney tissue following doxorubicin treatment and the effects of vitamin D on kidney tissue and TRPV1 channels. In this study, 24 adult male Wistar Albino rats were used. The animals were divided into four groups of six animals. During the 14-day experiment period, Group I did not have any application. 200 IU/day cholecalciferol was administered orally to Group II. Group III received 10 mg/kg single dose of DXR intraperitoneally (IP); and Group IV had a single 10 mg/kg dose of IP DXR and 200 IU/day of oral cholecalciferol. At the end of the experiment, the rats were decapitated, and their kidney tissues were removed. TRPV1 expression and apoptosis were detected in the tissue section by using immunohistochemical, TUNEL and real time-PCR (RT-PCR) techniques. The findings were examined and photographed with BH2 Olympus photomicroscope. As result of immunohistochemical staining, RT-PCR and examination with light microscope, it was found that the TRPV 1 immunoreactivity of the DXR group decreased in comparison with the control group, and the vitamin D application did not reverse this effect. Apoptosis detected by the TUNEL method tended to increase in the doxorubicin group and was relatively reversed with the administration of vitamin D. Tissue malondialdehyde (MDA) levels were observed to correlate with the findings of apoptosis. This study showed that vitamin D has anti- apoptotic and antioxidant effects on kidney tissue after DXR-induced injury. PMID- 26550294 TI - Effect of subarachnoid hemorrhage on voltage-dependence calcium channel current in cerebral artery smooth muscle cells. AB - OBJECTIVE: To investigate the effect of subarachnoid hemorrhage (SAH) on voltage dependent calcium channel (VDCC) current in cerebral artery smooth muscle cells (SMCs), oxyhemoglobins (OxyHb) concentration and vasospasm. METHOD: Thirty-six clean SD rats were used to establish SAH model by injecting autologous arterial blood into suprasellar cistern with the aid of stereotaxic instrument. They were divided into arterial SAH group (14 rats), venous SAH group (13 rats) and sham operation group (9 rats), and OxyHb concentrations were measured in the first two groups. Relative membrane surface area of cerebral artery SMCs, resting potential and VDCC current were measured using a patch clamp at day 3 after modeling; cerebral blood flow (CBF) was measured by using fluorescent microsphere-based lateral flow assay. RESULTS: OxyHb concentration of arterial SAH group (127+/-4 g/L) was higher than that of venous SAH group (54+/-6 g/L) and sham operation group (50+/-5 g/L), with significant difference (P<0.05); The maximum VDCC current (3.22+/-0.31 pA/pF) of the arterial SAH group was obviously higher than that of venous SAH group (2.19+/-0.27 pA/pF) and sham operation group (2.18+/ 0.29 pA/pF), also showing a significant difference (P<0.05). For arterial SAH group, VDCC current consisted of L- and R-type calcium current, and for venous SAH group the VDCC current consisted of L-type calcium current; CBF of arterial SAH group (0.83+/-0.14 ml/g/min) was significantly higher than that of venous SAH group (1.28+/-0.28 ml/g/min) and sham operation group (1.35+/-0.19 ml/g/min) (P<0.05). CONCLUSION: The effect of arterial SAH was greater on the expression and function of VDCCs in cerebral artery SMCs than venous SAH. This may be explained by the differences in the concentration and composition of pathogenic agents for vasospasm in the arterial and venous blood, such as OxyHb. PMID- 26550295 TI - Long-term follow-up after laparoscopic versus open distal gastrectomy for advanced gastric cancer. AB - This study aimed to compare the long-term outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer. Between January 2007 and December 2014, patients with advanced gastric cancer underwent distal gastrectomy by laparoscopic or open approach were identified. Patients in both groups were selected after being matched by age, gender, American Society of Anesthesiologists (ASA) class and clinical TNM stage using propensity score method, to create two comparable groups: laparoscopy and open groups, and prognosis were compared between these two groups. After the patients were matched, 86 patients in each group were selected for analysis. There were no significant differences in the clinicopathological features between the two groups. There were significant differences between the laparoscopy and open groups in terms of blood loss, duration of surgery, and hospital stay. The 5-year overall survival rate was 59% in laparoscopy group, and 56% in open group (P=0.523). The 5-year disease-free survival rate was 52% and 46%, respectively (P=0.362). According to the univariate and multivariate analysis, this type of surgical approach was not a prognostic factor for long-term outcomes. The current results indicated that laparoscopic distal gastrectomy is associated with similar overall survival and disease-free survival for advanced gastric cancer. PMID- 26550296 TI - Video-assisted thoracoscopic surgery versus open resection of lung metastases from colorectal cancer. AB - This study aimed to compare the short and long-term survival outcomes between video-assisted thoracoscopic surgery (VATS) and open resection of lung metastases from colorectal cancer. Between January 2006 and January 2013, 57 patients underwent VATS of lung metastases from colorectal cancer. These patients were compared with a consecutive matched group of 57 patients who underwent open resection within the same period. The two groups were similar in terms of age, gender, tumor size, number of tumors, tumor laterality and type of pulmonary resections. The operative time was longer in the VATS group, but the estimated blood loss was less in the VATS group than in the open group. Postoperative 30 day mortality, 30-day complications were similar between the groups. More complications were classified as major in patients underwent open resection, though the difference was not significant (P = 0.297). The 5-year overall survival rate was 50% for VATS and 46% for open resection (P = 0.251). The 5-year overall disease-free survival time was similar in two groups (P = 0.457). The findings suggest that VATS is associated with less blood loss than open resection for lung metastases of colorectal cancer. According to our results, VATS for lung metastases from colorectal cancer is equivalent to open resection in terms of long-term survival outcomes. PMID- 26550297 TI - Short and long-term outcomes after gastrectomy for gastric carcinoma in elderly patients. AB - As worldwide life expectancy rises, the number of candidates for surgical treatment of gastric carcinoma over 70 years will increase. This study aims to examine outcomes after gastric carcinoma in elderly patients. This study is a retrospective review of 697 patients undergoing gastrectomy with radical intent for gastric carcinoma during January 2007 to January 2013. A total of 534 patients were less than 70 years old (group A), and 163 patients 70 years or greater (group B). We analyzed the effect of age on short and long-term variables including overall survival and disease-free survival. Major morbidity was observed to occur in 19 patients of group A, and 15 of group B. Mortality, both 30-day and 90-day was observed in 1 and 3 of group A, and 3 and 6 of group B. Five-year overall survival and disease-free survival was 61% and 60% for group A, 50% and 43% for group B respectively. Gastrectomy should be carefully considered in patients 70 years old and can be justified with low mortality and acceptable long-term outcomes. PMID- 26550299 TI - Relationship between lipoprotein lipase gene polymorphism and hemorrhagic stroke in a Chinese population. AB - OBJECTIVE: To investigate the relationship between lipoprotein lipase (LPL) gene polymorphism and cerebral hemorrhage in a Chinese population. METHOD: This study was based on the case-control study, PCR-RELP and sequencing method were utilized for genotyping. LPL gene Hind III polymorphism was detected both in 300 patients with cerebral hemorrhage (CH group) and in 300 healthy control subjects (control group). Blood lipid level and blood glucose were detected at the same time. RESULT: Our results showed that G allele frequency was significant lower in the CH group than that in the control group (OR=0.611; 95% CI: 0.427-0.876, P=0.001). We also found both GG (OR=0.543, 95% CI: 0.233-0.988; P=0.041) and TG (OR=0.609, 95% CI: 0.387-0.959, P=0.032) genotype were frequent in the control group than that in the CH group. TG level of the groups who carry TT genotype were much higher than that of the groups carrying TG+GG genotype (P<0.05). By means of adjusting age, hypertension and hyperglycemia, logistic multivariate regression analysis revealed that LPL Hind III G allele might be a protective factor (OR=0.601, 95% CI: 0.231-0.876; P=0.001) in the present study. CONCLUSION: It is suggested that LPL Hind III G allelic mutation might be a protective factor against cerebral hemorrhage disease in Chinese population. PMID- 26550298 TI - Creative arts program as an intervention for PTSD: a randomized clinical trial with motor vehicle accident survivors. AB - The aim of this study is to determine whether the creative arts program (HA) is effective in preventing the onset of Posttraumatic stress disorder (PTSD). PTSD develops in 10-20% of motor vehicle accident survivors (MVAs). MVAs in the initial months after the accident were randomly assigned to receive 8-week HA intervention (n = 26) or wait the list (WL, n = 26). The arts program consisted of writing and drawing. PTSD severity was assessed at 2, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale, CAPS) and self-report instrument (Impact of Event Scale-Revised, IES-R). Secondary outcomes were post-traumatic growth (PTG), depression and anxiety symptoms. Repeated measures analysis of variance indicated that both HA and WL group exhibited a significant effect of time (P < 0.01) on CAPS, but no significant group differences over time. There were no group differences on depression or anxiety over time. Pessimists did not benefit more from attending the HA than they did from attending the WL. Our results fail to support the hypothesis that the creative arts program is effect in avoiding MVA-related PTSD symptoms. But it only seems to be a short-term, rather than a long-term effect. PMID- 26550300 TI - Clinical value of microRNA-23a upregulation in non-small cell lung cancer. AB - BACKGROUND: MiR-23a function as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC. METHODS: Tissue samples were obtained from 127 NSCLC patients who underwent complete resection at Yantaishan Hospital from March 2008 to January 2014. The expression level of miR 23a was detected in NSCLC tissues and the matched adjacent lung tissues by qRT PCR. The survival analysis was estimated by the Kaplan-Meier method and was compared by using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The expression level of miR-23a was significantly up-regulated in NSCLC tissues compared with matched adjacent lung tissues (P<0.001). The expression of miR-23a in NSCLC tissues was significantly associated with the smoking status (P=0.001), tumor size (P=0.002), lymphnode metastasis (P<0.001), TNM stage (P=0.001), and tumor differentiation (P=0.004). The overall survival was significantly lower in patients with higher miR-23a expression than in patients with lower miR-23a expression (P=0.02). In addition, multivariate analysis demonstrated that high miR-23a expression (HR=3.558, 95% CI: 2.982-6.635, P=0.011) was significant prognostic factor for NSCLC patients. CONCLUSIONS: miR-23a might play an oncogenic role in NSCLC and is a poor prognostic factor. Our results must be verified by large-scale prospective studies with standardized methodology. PMID- 26550301 TI - Video-assisted thoracoscopic surgery for non-small-cell lung cancer is beneficial to elderly patients. AB - The aim of this study was to explore whether video-assisted thoracoscopic surgery (VATS) has short or long-term benefits in elderly patients with non-small-cell lung cancer compared with open surgery. Between June 2007 and December 2014, 579 patients older than 70 years underwent radical pulmonary resection for non-small cell lung cancer, including 138 who received VATS and 441 who received open surgery. A retrospective pair-matched study was performed to compare 194 patients (97 pairs) who underwent either VATS or open resection. Patients were matched by age, sex, comorbidity, American Society of Anesthesiologists (ASA) score, tumor location, clinical TNM stage, and extent of pulmonary resection. Short and long term outcomes were compared between the two groups. The overall incidence of postoperative 30-day complications was significantly lower in the VATS group than in the open surgery group. The major postoperative 30-day complication trended lower in the VATS group but was not significantly different. The length of postoperative hospital stay was significantly shorter. Kaplan-Meier analysis showed that 5-year disease-free survival and overall survival was similar between the two groups. In summary, in surgical management of elderly patients with non small-cell lung cancer, VATS is associated with lower rates of morbidity as well as comparable disease-free survival and overall survival outcomes. PMID- 26550302 TI - Allopregnanolone attenuates Abeta25-35-induced neurotoxicity in PC12 cells by reducing oxidative stress. AB - Massive accumulation of amyloid beta (Abeta) has been implicated as a pivotal event in the pathogenesis of Alzheimer's disease. The underlying mechanisms of Abeta-induced neurotoxicity include generation of reactive oxidative species (ROS), inflammation, and neurons loss. Allopregnano-lone (APalpha), a neurosteroid derive from neuroactive progesterone, has been demonstrated to have neuroprotective properties in vivo and vitro. In the present study, the effects of APalpha on oxidative damage in Abeta25-35-treated pheochromocytoma (PC12) cells were investigated. Pretreatment of APalpha significantly attenuated Abeta25 35-induced neuronal death. APalpha decreased the intracellular ROS generation and reduced lipid peroxidation induced by Abeta25-35. In addition, APalpha treatment enhanced antioxidant enzyme superoxide dismutase (SOD) activity. This study demonstrates that APalpha exerts a protective effect against Abeta25-35-induced neurotoxicity in PC12 cells. The protective role of APalpha likely results from inhibition of oxidative stress. PMID- 26550303 TI - Effect of low dose rocuronium in preventing ventilation leak for flexible laryngeal mask airway during radical mastectomy. AB - The flexible laryngeal mask airway (FLMA) is becoming more and more popular in general anesthesia during surgery of head, neck and upper chest. But very limited information has been published about whether muscle relaxant was necessary or not for anesthesia with FLMA. To investigate whether low-dose muscle relaxant is necessary in preventing ventilation leak of FLMA in radical mastectomy, forty eight female patients undergoing radical mastectomy were enrolled in the study. They were randomly divided into low-dose muscle relaxant (LD-MR) group and non muscle relaxant (non-MR) group. All the included patients received total intravenous anesthesia (with propofol, fentanyl and remifentanil) and controlled mechanical ventilation with FLMA during the surgery. Patients in LD-MR group received 0.4 mg/kg rocuronium during anesthesia induction, while patients in non MR group received equivalent volumes of physiological saline. Insertion time was shorter in LD-MR group than that in non-MR group (P < 0.05). Peak airway pressures and ventilation leak volumes at 10, 20 and 30 minutes were lower in LD MR group than those in non-MR group (P < 0.05). No difference was found between LD-MR and non-MR group in terms of emergence time, FLMA extraction time, and maximum tidal volumes before FLMA extraction. The results show that low-dose rocuronium could reduce the ventilation leak for mechanical ventilation with FLMA during radical mastectomy without prolonging the emergence time. PMID- 26550304 TI - Does transcutaneous electric acupoint stimulation improve the quality of recovery after thyroidectomy? A prospective randomized controlled trial. AB - BACKGROUND: We evaluated the effects of transcutaneous electric acupoint stimulation (TEAS) on the postoperative quality of recovery after thyroidectomy with general anesthesia in this prospective, randomized, double-blind, placebo controlled study. METHODS: Eight-four American Society of Anesthesiologists physical status (ASA) I or II patients undergoing thyroidectomy were randomly allocated to TEAS or control groups. The primary outcome was the quality of recovery, which was assessed on the day before surgery and 24 h after surgery using the Quality of Recovery 40 questionnaire (QoR-40). Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), postoperative pain intensity, duration of post anesthesia care unit (PACU) stay and patient's satisfaction. RESULTS: Global QoR-40 score at 24 h after surgery was higher in the TEAS group (median [interquartile range], 183 [172-190]) compared with the control group (168 [154-183]) (P < 0.001). Compared with the control group, postoperative pain intensity and the cumulative number of opioids administered was lower in the TEAS group patients (P < 0.001). TEAS reduced the incidence of PONV and dizziness (P = 0.001), as well as the duration of PACU stay (P < 0.001). Simultaneously, the patient's satisfaction scores were higher in the TEAS group (P = 0.002). CONCLUSION: Preoperative TEAS enhances the quality of recovery, postoperative analgesia and patient's satisfaction, alleviates postoperative side effects and accelerates discharge after general anesthesia for thyroidectomy. PMID- 26550305 TI - Pre-miR-149 rs71428439 polymorphism is associated with increased cancer risk and AKT1/cyclinD1 signaling in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common lethal malignancies in the world, and the current knowledge on the molecular and genetic basis of HCC is still limited. Previous study has shown miR-149 plays a tumor suppressive role in HCC, here we aimed to investigate the association between rs71428439 polymorphism, which located in the pre-miR-149, and the risk of HCC in a Chinese Han population. A total of 177 HCC patients and 103 healthy controls were genotyped, by a multivariate logistic regression, we found that individuals with GG genotype have significantly higher risk of HCC (adjusted OR=3.397, 95% CI=1.565-7.375, P=0.002) compared with those with AA genotype, similar results were also observed in recessive model (adjusted OR=2.563, 95% CI=1.300-5.054, P=0.007) and dominant model (adjusted OR=2.074, 95% CI=1.147-3.752, P=0.016). We further observed that tumor tissues in patients with GG genotype expressed lower level of miR-149 compared with those with AA or AG genotype, and consequently, AKT1, a pre-validated miR-149 target in vitro, was found to have higher expression level in tumors with GG genotype. In summary, our data indicated that rs71428439 may be a genetic risk factor of HCC in the Chinese Han population, and its mechanism possibly involves downregulated miR-149 expression and upregulated AKT1 expression. PMID- 26550306 TI - Effects of sevoflurane preconditioning on lung injury during one lung ventilation. AB - BACKGROUND: To study the lung protective effects of heme oxygenase-1 (HO-1) expression and sevoflurane preconditioning in patients with lobectomy. METHODS: 30 patients receiving lobectomy were divided into two groups: propofol intravenous anesthesia group (Pro group) and sevoflurane preconditioning group (Sev group). In Pro group, propofol was used for intravenous anesthetic. In Sev group, 1%-2% sevoflurane was used during anesthesia induction to one lung ventilation (OLV). Venous blood was taken before OLV (T1), at the end of OLV (T2) and at 30 min after lung ventilation (T3) to measure the concentration of serum malondialdehyde (MDA) in two groups. HO-1 protein and mRNA expression in resected lung tissue were measured with PT-PCR and Western blot technique. Oxygenation index was detected at 2 hours after operation. RESULTS: HO-1 protein (2.88+/-0.23 ng/ml) and mRNA expression in Sev group were significantly higher compared to protein (1.89+/-0.12 ng/ml)and mRNA expression in Pro group (P<0.05). Difference was not found in MDA concentration at T1 compared to T2 (P>0.05), however, at T3, MDA concentration was higher in Pro group than that in Sev group (P<0.05). oxygenation index in Sev group was 380+/-67 mmHg, which was significantly different from that in Pro group (290+/-56 mmHg) (P<0.05). CONCLUSION: Sevoflurane preconditioning can reduce oxidative stress injury induced by OLV and protect lung tissue by increasing HO-1 expression in lung tissue. PMID- 26550307 TI - Correlation of axial length and corneal curvature with diopter in eyes of adults with anisometropia. AB - PURPOSE: To analyze the causes of anisometropia. METHODS: Between June 2011 and November 2012 101 participants were divided into three groups. The refraction comprising the degree of refractive errors in the presence of astigmatism which was converted into the degree of spherical equivalent as well as ocular axial length (AL), corneal curvature (CR), average corneal power (ave K) and diopters were measured. RESULTS: The differences of ocular AL/CR and CR between two eyes were statistically significant among the three groups (P < 0.05). Standardized regression coefficients obtained by a multiple linear regression analysis indicated that AL/CR, AL and ave K differences correlated with anisometropia in descending order. CONCLUSION: The difference of AL/CR ratios between the eyes was the main cause for anisometropia, followed by AL and ave K values. PMID- 26550308 TI - Correlation of NGX6 expression with clinicopathologic features and prognosis in colon cancer. AB - OBJECTIVE: The aim was to explore the correlation of NGX6 expression with clinicopathological features and prognosis in colon cancer. METHODS: Clinicopathological feature of 145 patients with colon cancer were analyzed.NGX6 expression was measured using immunohistochemistry methods. The correlation of NGX6 expression with clinicopathological features and prognosis were assessed. RESULTS: Among 145 cases of colon cancer, NGX6 positive expression were found in 76 (52.4%) cases and NGX6 negative expression were found in 69 (47.6%) cases. The expression of NGX6 was closely associated with size tumor, lymph node metastasis and TNM stage (P=0.002, 0.012, and 0.039, respectively). Kaplan-Meier analysis showed that NGX6 negative expression was associated with shorter disease-free survival (DFS) (P=0.029) and overall survival (OS) (P=0.015). Multivariate survival analysis demonstrated that NGX6 expression was the important independent prognostic factor for colon cancer (P=0.022). CONCLUSION: NGX6 is involved in the invasion and metastasis activity of colon cancer. NGX6 could may be applied as a novel and promising prognostic marker for colon cancer. PMID- 26550309 TI - Incidence of abdominal incisional hernia in developing country: a retrospective cohort study. AB - OBJECTIVE: To estimate the incidence of abdominal incisional hernia in developing countries. METHODS: This population-based retrospective cohort study identified all patients with abdominal surgery between 2006 to 2011 in Aden Public Hospital, Aden, Yemen and the Second Hospital Affiliated with Dalian Medical University, Dalian, China. The cohort was followed from their first until 1 year after their last abdominal surgery within the inclusion period or until the first of the following events: hernia repair, death, emigration, second abdominal surgery. For patients who had a hernia repair, hospital records regarding the surgery and previous abdominal surgery were tracked and manually analyzed to confirm the relationship between hernia repair and abdominal surgery. RESULTS: We identified 2096 patients who had abdominal surgery during the inclusion period and 51 cases were excluded. During follow-up, 80 of these patients who had a hernia requiring repair were analyzed. Of these 20 had infected incision and 80 had non-infected incision. The incidence is significantly higher in infected incision (20/202) than that in non-infected incision (60/1843). There were no any differences in the incidence between Aden and Dalian. CONCLUSIONS: The overall incidence of abdominal incisional hernia requiring surgical repair within 1 year after abdominal surgery was 80/2045 in a population from Aden and Dalian. Infected incision is prone to occur incisional hernia during the follow-up period. PMID- 26550310 TI - A new technique for immediate endoscopic realignment of post-traumatic bulbar urethral rupture. AB - OBJECTIVES: Urethral injury with partial or complete disruption of urethral integrity can lead to voiding problems and serious infections. We report a new management technique involving immediate endoscopic realignment with drainage via peel-away sheath for post-traumatic bulbar urethral rupture. METHODS: Thirteen patients presenting with post-traumatic bulbar urethral rupture between July 2010 and May 2013 were treated. An 18F peel-away sheath was inserted into the anterior urethra, then a ureteroscope or nephroscope was inserted into the peel-away sheath with continuous normal saline infusion and drainage through the cavity between ureteroscope and sheath to maintain operative field clarity. A guide wire was negotiated across the disruption to the bladder and an 18F Foley catheter inserted for 2-4 weeks. Rupture severity was evaluated by urethroscopy during operation. Two patients had partial urethral rupture and 11 complete rupture. Before Foley catheter removal, pericatheter urethrography was performed to determine if urinary extravasation had occurred. Urethroscopy was performed after catheter removal. Follow-up uroflowmetry was conducted monthly for 1 year. RESULTS: This technique was successful in all patients and none experienced urinary extravasation or required open surgery. Mean operation time was 4.9+/-1.6 min (3-8 min) and the mean Foley catheter indwelling time was 25.8+/-5.3 days. During follow-up (18.4+/-5.4 months, 12-26 months), 6 patients developed urethral strictures (8.7+/-10.5 weeks, 1-28 weeks post-treatment). Strictures were managed by internal urethrotomy (1 patient) or urethral sound dilation (5) without open urethroplasty. CONCLUSIONS: Immediate endoscopic realignment with drainage via peel-away sheath is a fast, effective, and safe technique for bulbar urethral rupture. PMID- 26550311 TI - Surgical interventions for gastric cancer: a review of systematic reviews. AB - AIM: To evaluate methodological quality and the extent of concordance among meta analysis and/or systematic reviews on surgical interventions for gastric cancer (GC). METHODS: A comprehensive search of PubMed, Medline, EMBASE, the Cochrane library and the DARE database was conducted to identify the reviews comparing different surgical interventions for GC prior to April 2014. After applying included criteria, available data were summarized and appraised by the Oxman and Guyatt scale. RESULTS: Fifty six reviews were included. Forty five reviews (80.4%) were well conducted, with scores of adapted Oxman and Guyatt scale >= 14. The reviews differed in criteria for avoiding bias and assessing the validity of the primary studies. Many primary studies displayed major methodological flaws, such as randomization, allocation concealment, and dropouts and withdrawals. According to the concordance assessment, laparoscopy-assisted gastrectomy (LAG) was superior to open gastrectomy, and laparoscopy-assisted distal gastrectomy was superior to open distal gastrectomy in short-term outcomes. However, the concordance regarding other surgical interventions, such as D1 vs. D2 lymphadenectomy, and robotic gastrectomy vs. LAG were absent. CONCLUSION: Systematic reviews on surgical interventions for GC displayed relatively high methodological quality. The improvement of methodological quality and reporting was necessary for primary studies. The superiority of laparoscopic over open surgery was demonstrated. But concordance on other surgical interventions was rare, which needed more well-designed RCTs and systematic reviews. PMID- 26550312 TI - A single-center experience of hemofiltration treatment for acute aortic dissection (Stanford type A) complicated with postoperative acute renal failure. AB - OBJECTIVE: To investigate the effect of continuous venovenous hemofiltration (CVVH) for aortic dissection patients with acute renal failure after surgery in retrospective manner. METHODS: A total of thirty-seven aortic dissection patients with postoperative acute renal failure accepted CVVH therapy. The effect of CVVH was evaluated by analyzing clinical condition changes and laboratory examination results. RESULTS: After treatment of CVVH, renal function and clinical symptoms were significantly improved in thirty patients. Eight of the thirty patients got completely renal function recovery within two weeks after CVVH therapy; and twenty-two of the thirty patients got completely renal function recovery within four weeks after CVVH therapy. Nevertheless, seven patients got no benefit from CVVH therapy with poor prognosis. CONCLUSION: CVVH is an effective treatment to most aortic dissection patients with postoperative acute renal failure. The effect of CVVH was correlated with original renal function, early CVVH therapy, and continuous intensive care. PMID- 26550313 TI - Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population. AB - Cholangiocarcinoma (CCA) is the most common malignant heterogeneous polygenetic carcinoma with a high incidence in Asia. Most patients would die within 1 year after diagnosis and the 5 year survival rate is less than 10-20% worldwide. Single nucleotide polymorphisms (SNPs) in genes regulate telomere maintenance, mitosis, and inflammation, and may help predict individual susceptibility to certain drugs, environmental factor, and risks to particular diseases. The gene gene interaction and the regulation of SNPs have not been assessed extensively in CCA. According to our previous study, the GRB2-associated-binding protein (Gab1) gene rs3805246 (X(2) =5.015, P=0.025, OR=0.531, 95% CI 0.304-0.928) and epidermal growth factor receptor (EGFR) gene rs2007000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675) presented significant difference between CCA patients and controls. This study conducted a population-based analysis using 225 CCA cases (153 biliary tract cancer patients and 72 gall bladder cancer patients) to assess the association between SNPs and progression of CCA patients, including the overall survival and the prognosis analysis. Results showed that an increased susceptibility of BTC was significantly associated with SNP loci distribution frequency in EGFR rs2107000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675). Furthermore, multivariate factor regression analysis represented cholelithiasis medical history of BTC patients can be an effective evaluation criteria of BTC susceptibility in early stage. This study also assessed the relationship between these genotypic polymorphisms and clinicopathologic data, including tumor differentiation stage and overall survival. This is the first study identifying that EGFR polymorphisms are associated with BTC and EGFR rs2017000 polymorphisms may be an important survival predictor in BTC patients. PMID- 26550314 TI - Clinical efficacy and safety of paclitaxel plus carboplatin as neoadjuvant chemotherapy prior to radical hysterectomy and pelvic lymphadenectomy for Stage IB2-IIB cervical cancer. AB - OBJECTIVE: To assess the efficacy and toxicity of the combination of paclitaxel plus carboplatin as neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC) prior to radical hysterectomy and pelvic lymphadenectomy. METHODS: We reviewed patients with cervical cancer of the International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IIB who underwent neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin followed by radical hysterectomy (NACT group) or only received primary radical surgery (PRS group) in our hospital between Jan 2007 and Jan 2012. Toxicity, NACT response, surgery pathological factors and survival data were collected and analyzed. RESULTS: In the NACT group, the overall response rate was 71.3% (82/115). Eighteen (15.7%) patients achieved complete remission. Well differentiated tumors showed a more favorable response to NACT (P=0.011). Myelosuppression was the most common adverse effect (51.7%) and serious adverse effects were rare (3.4%). The median follow-up period was 44 months (range, 6-75). The NACT responders had significantly longer OS and PFS when compared to the non-NACT responders and patients in the PRS group. CONCLUSION: Patients with LACC can benefit from neoadjuvant chemotherapy with paclitaxel plus carboplatin when they have response to the chemotherapeutic agents. PMID- 26550315 TI - Estimating the burden of invasive Group B Streptococcal disease in young infants in southern mainland China: an observational study. AB - OBJECTIVES: To estimate the incidence, case fatality ratio and serotypes associated with early-onset (EOD) and late-onset (LOD) invasive GBS disease in infants in southern mainland China. METHODS: During the six-month study period, infants aged <= 90 days with culture-confirmed GBS disease born in the study hospitals or elsewhere, but presenting to a study hospital, were enrolled. GBS positive cultures were genotyped, serotyped and sequence typed. The incidence rate was calculated for infants born in the study hospitals, and case fatality ratio and causative serotypes identified for all enrolled GBS cases. RESULTS: Ten cases were enrolled: 2 EOD cases born in the study hospitals and 8 LOD cases born elsewhere. Incidence rate was 0.28 (95% confidence interval: 0.08-1.03, n = 2/7061 successfully followed-up consenting subjects); no cases resulted in fatality. In the 8 GBS isolates available for typing, 4 serotypes (Ia, Ib, III and V) and 5 multi-locus sequence types (1, 10, 12, 17 and 23) were identified. CONCLUSIONS: This is the first study specifically investigating the incidence of GBS invasive disease in infants in southern mainland China. Incidence and case fatality were low but further research is needed in larger, more diverse cohorts to estimate disease burden for the broader Chinese population. PMID- 26550316 TI - Extended anterolateral approach for treatment of posterolateral tibial plateau fractures improves operative procedure and patient prognosis. AB - PURPOSE: The treatment of posterolateral tibial plateau fracture remains controversial and challenging. Several approaches for this fracture have been applied for direct exposure and support plate fixation. However, several structures are to be at risk via posterior approach, which may affect exposure and plate application. To solve this problem, an extended anterolateral approach was developed and reported. METHODS: 15 patients with posterolateral tibial plateau fractures treated with this approach were reviewed. The primary outcomes, such as Rasmussen functional score, and the secondary outcomes, such as knee deformity, postoperative infection, as well as complications were evaluated. RESULTS: All 15 cases have been followed up for 12 to 30 months (19.7 months at average). Rasmussen functional score after surgeries was 25.0 +/- 2.8 points. A score >= 27 points was considered as excellent (ten patients), a score of 20-26 points (four patients) was considered as good; and a score of 10-19 points (one patient) was considered as fair. Anatomic reductions were obtained in 14 patients, but a 3 mm gap was found in one patient. For all patients, there were no wound complications, nonunion, valgus knee deformities, plate loosening or breakages, or fracture re-displacements. No vascular or neural injuries occurred in any patient. CONCLUSION: The extended anterolateral approach provides excellent visualization, which can facilitate the internal fixation and reduction of posterolateral tibial plateau fractures, and shows encouraging results. PMID- 26550317 TI - Efficacies and adverse reactions of modified vitamin supplement programs before pemetrexed chemotherapy as a second-line treatment against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma. AB - OBJECTIVE: This study aims to observe the efficacies and adverse reactions of modified vitamin programs before pemetrexed chemotherapy (second-line treatment) against epidermal growth factor receptor (EGFR) mutant wild-type lung adenocarcinoma. METHODS: 477 patients with IIIB, phase IV glomerular filtration rate (GFR) mutant-negative lung adenocarcinomas and performed pemetrexed chemotherapy were collected and divided into group A (167 cases, with modified program) and group B (310 cases, with traditional program). The modified program was: orally administrated 400 MUg folic acid once per day and 1 day before the first-round pemetrexed chemotherapy, until the 21st day of the final administration of pemetrexed, and intramuscularly injected 500 MUg vitamin B12 1 day before the first-round pemetrexed chemotherapy, and injected once 1 day before every round pemetrexed treatment. RESULTS: Comparison between group A and group B: mean chemotherapy cycles (4.08 vs 3.98); effectiveness rate (22.16% vs 22.90%); disease control rate (56.51% vs 55.00%); without significant difference (P > 0.05). Two groups currently all reached the median overall survival (OS). The median progression-free survival (PFS): 4.2 vs 4.1 months; OS: 12.9 vs 13.2 months, without statistical difference (P > 0.05). Such side effects between the two groups as leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, fatigue, creatinine increasing, alanine transaminase (ALT) increasing, stomatitis, peripheral neuropathy, alopecia and rash had no significant difference (P > 0.05). CONCLUSIONS: The modified vitamin supportive treatment could ensure the efficacy, significantly simplify, facilitate the clinical application, and increase the associated toxicities, indicating that the pemetrexed-based chemotherapy did not need to be delayed because applying the vitamin supportive treatment. PMID- 26550318 TI - Comparison of functional magnetic resonance imaging in cerebral activation between normal Uygur and Mandarin participants in semantic identification task. AB - PURPOSE: This study utilized blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) technology to study the activated cerebral regions in normal participants whose native language was Uyghur or Chinese. METHODS: We collected the fMRI data from 15 Uyghur-speaking volunteers and 15 Mandarin-speaking volunteers when executing the semantic identification task and compared the results of two groups. RESULTS: Statistically significant difference of brain activation was found primarily in the left anterior cingulate gyrus (BA23) and the midline precuneus (P<0.05). When performing the semantic identification task, the Uyghur group exhibited significant activation in these two regions, whereas the Chinese group demonstrated relatively weak activation in these areas. CONCLUSION: The cerebral regions activated by Uyghur and Chinese semantic identification are not identical, the dominant hemisphere for both languages is the left cerebral hemisphere. The left anterior cingulate gyrus might have a language function in Uyghur semantic processing. PMID- 26550319 TI - Correlation of macrophage inflammatory protein-1alpha single gene polymorphisms with the susceptibility to pigeon breeder's lung in chinese uygur population. AB - OBJECTIVE: To investigate the correlation of macrophage inflammatory protein 1alpha (MIP-1alpha) gene single nucleotide polymorphisms (SNP) with the susceptibility to pigeon breeder's lung (PBL) in Chinese Uygur population. METHODS: A total of 92 Uygur from Xinjiang, China were enrolled in the study. Among them, there were 32 patients with PBL, 30 negative controls with history of exposure to pigeons and 30 normal controls without pigeons contact. SNP genotyping for 24 SNPs of MIP-1alpha were performed. RESULTS: Genotype distribution of MIP-1alpha SNPs rs1049191, rs1049195, rs3210166, rs1130374 and rs5029407 were significantly different among the three groups (P<0.05). CONCLUSION: MIP-1alpha SNPs rs1049191, rs1049195, rs3210166, rs1130374 and rs5029407 might have correlation with the susceptibility to pigeon breeder's lung in Chinese Uygur population. PMID- 26550320 TI - Does uterine gauze packing increase the risk of puerperal morbidity in the management of postpartum hemorrhage during caesarean section: a retrospective cohort study. AB - BACKGROUND: To compare the outcomes especially the puerperal morbidity of uterine gauze packing (UGP) with those of uterine balloon tamponade (UBT) in the management of postpartum hemorrhage (PPH) during caesarean section (c-section). METHODS: It was considered success as no requirement for either a further therapy or hysterectomy for PPH. The postpartum infection risk was pragmatically measured as puerperal morbidity. RESULTS: The identified PPH subjects were subdivided into two groups for comparison, in which UGP or UBT was used as second-line therapy for women undergoing c-sections between January 2010 and September 2014. Of the 318 c-section subjects initially treated by basic managements for expected PPH, 99 cases underwent UGP and 66 UBT as the second-line therapies to stop persistent bleeding. The success rates of the UGP and UBT groups were 90.91 and 87.88%, respectively. Only one patient in UBT group resorted to hysterectomy. The respective rates of puerperal morbidity were 10.10 and 13.64%, with risk ratio of 0.74 (95% CI: 0.32, 1.72). There were no significant differences between the two groups even after the adjustment for potential confounding factors. CONCLUSION: UGP appears to be effective in treating PPH during c-section without an observed increase in the risk of potential postpartum infection when compared with UBT. UGP could be recommended as routine for patients who are not responding to conventional basic therapies in addressing PPH, along with the provision of appropriate training. PMID- 26550321 TI - Interference of strength training can obviously increase the effect of moxibustion treatment on patients with knee joints injuries. AB - OBJECTIVE: Observe the effects of Acupoint moxibustion combined with muscle training in treating the patients with knee joints strain. METHODS: The 36 patients with knee joint strains were divided into the experimental group and control group with the method of random number table, each group including 18 cases. The control group was treated with Acupoint moxibustion, while the experimental groups were treated with Acupoint moxibustion combined with muscle training. Before the treatment and after the treatment lasting 12 weeks, the therapy effects and improvement of the knee-joint muscle force for the 2 groups of patients were respectively evaluated. RESULTS: Through the treatment of 12 weeks, the clinical symptoms of control group were evidently improved than prior treatment , but the improvement effects of the knee-joint muscle force (the peak torques of bend and stretch respectively were (32.8 +/- 8.8) N.m and (35.0 +/- 11.2) N.m were not significant (P > 0.05); while the clinical symptoms and knee joint muscle force of experimental group (the peak torques of bend and stretch respectively were (40.3 +/- 9.3) N.m and (42.3 +/- 10.6) N.m were evidently improved than prior-treatment, and the improvement range was also evidently better than the control group (P < 0.05). CONCLUSION: The Acupoint moxibustion combined with muscle force training had synergistic effects in treating the patients with elderly knee-joint strain, could further relieve the pain on knee joints, and improve the joint' s movement, such therapy was worthy to promote and apply in clinic. PMID- 26550322 TI - Neuropsychological profile in Chinese patients with Parkinson's disease and normal global cognition according to Mini-Mental State Examination Score. AB - OBJECT: Cognitive impairments have been reported to be more common in non demented patients with Parkinson's disease (PD) and education levels play an important role in intelligence. The studies on cognitive impairments in Chinese PD patients with higher education levels and normal global cognition according to Mini-Mental State Examination Score (MMSE) have not been reported. METHODS: We enrolled 69 consecutive PD patients with over 6 years education levels and a MMSE score above 24 (of 30) and performed a battery of neuropsychological scales. RESULTS: There are extensive cognitive domain impairments in PD patients with "normal" global cognitive according to MMSE. Montreal Cognitive Assessment (MoCA) is a highly sensitive scale to screen cognitive impairments in PD. CONCLUSION: The cutoff score of 28 on the MMSE screening for cognitive impairment in Chinese PD patients with high education levels may be more appropriate. PMID- 26550323 TI - Predictors of slow flow in angiographically normal coronary arteries. AB - INTRODUCTION: Slow coronary flow (SCF) is a well-known angiographic finding; however, the pathophysiology of SCF remains only partially understood. In this study, we have examined the risk factors of slow coronary flow. METHODS: Seventy patients with angiographically proven SCF were studied along with 60 control participants. Patients were divided into 2 groups based on the angiographic findings as with or without SCF. In both groups, clinical information was collected and laboratory parameters were measured and compared. RESULTS: Patients with SCF had higher serum uric acid, creatinine and hemoglobin levels. They also more commonly had a history of smoking. On the other hand, C-reactive protein and hematologic parameters such as mean platelet volume (MPV), red cell distribution width (RDW), and neutrophil to lymphocyte (N/L) ratio did not differ significantly between the two groups. In the logistic regression analysis, only uric acid (odds ratio [OR]=1.583, 95% confidence interval [CI]=1.011-2.349, P=0.034) was found as an independent correlate of SCF. CONCLUSIONS: This study demonstrates that serum uric acid level is significantly correlated with SCF and may play a role in the development of the condition. These findings provide impetus for additional studies to confirm these results and treatment of SCF. PMID- 26550324 TI - Influences of anterior capsule polishing on effective lens position after cataract surgery: a randomized controlled trial. AB - To evaluate the effects of anterior capsule polishing on effective lens position (ELP) and the actual axial movements of IOLs by measuring the anterior chamber depth (ACD). This prospective randomized double-blind controlled clinical trial included patients who underwent bilateral uneventful cataract surgeries and were implanted the same IOLs (SN60WF). Extensive polishing was performed randomly in the anterior capsule of one eye with Whitman Shepherd double-ended capsule polisher, and the opposite unpolished capsule was used as the control. The ACD was measured 1 day, 1 week, 1 month, 3 months and 6 months after surgery with the anterior segment optical coherence tomography (AS-OCT). The actual axial movement of IOL was defined as the root mean square (RMS) of the change in ELP at each visit. A total of 40 eyes of 20 patients were included, and 10 patients (50%) were men. All the patients underwent uneventful surgeries without intraoperative or postoperative complications, and returned on time for measurements. The mean age of them was 70.5+/-7.6 years (range 56 to 79 years). No significant differences were observed between the mean ELP of the control group and the polished group (P>0.05). Nevertheless, the ELPRMS of the polished group was significantly smaller than that of the control group (P=0.005). Polishing anterior capsule intraoperatively improved the axial position stability of the IOL in the long term. PMID- 26550325 TI - Influence of dexmedetomidine on incidence of adverse reactions introduced by hemabate in postpartum hemorrhage during cesarean section. AB - OBJECTIVE: The purpose of our study was to observe the influence of dexmedetomidine on complications caused by hemabate in patients undergoing caesarean section. METHODS: A total of 120 females (age range, 20-40 years) at 35 40 weeks gestation who delivered by cesarean between September, 2014 and December, 2014 were enrolled in our study. Patients were randomly allocated into three groups that received intravenously physiological saline 20 mL (placebo group), lower dose (0.5 MUg kg(-1)) of dexmedetomidine (low-dex gruop) and higher dose (1 MUg kg(-1)) of dexmedetomidine (high-dex group) during cesarean section, following the delivery of the infant and intramuscular hemabate injection. RESULTS: Nausea, vomiting, chest congestion and elevated blood pressure were the most common adverse events of placebo group. Compared with placebo group, the above mentioned adverse reactions decreased significantly in both low-dex group and high-dex group (P<0.05), whereas there were no significant difference between low-dex group and high-dex group (P>0.05). As to patient satisfaction score, low dex group and high-dex group were all higher than placebo group (P<0.05). Furthermore, there were more patients satisfied with high-dex group than low-dex group (P<0.05). CONCLUSION: Dexmedetomidine (0.5 MUg kg(-1) and 1 MUg kg(-1)) were all effective in preventing adverse reactions introduced by hemabate and improve parturients' satisfaction in patients undergoing cesarean delivery. And higher dose (1 MUg kg(-1)) of dexmedetomidine is superior to lower dose (0.5 MUg kg(-1)) in patient satisfaction. PMID- 26550326 TI - Efficacy of surfactant at different gestational ages for infants with respiratory distress syndrome. AB - Since exogenous surfactant replacement therapy was first used to prevent respiratory distress syndrome (RDS), it has become the main method for treatment of RDS. However, in some infants, death is inevitable despite intensive care and surfactant replacement therapy, especially in near-term and term infants. The main purpose of this study was to compare the therapeutic effect of pulmonary surfactant for infants at different gestational ages and to investigate whether exogenous surfactant replacement therapy is effective for all newborns with RDS. Data on surfactant replacement therapy, including blood gas, oxygenation function parameters and therapy results, were collected from 135 infants who were diagnosed with RDS during three years at a tertiary neonatal intensive care unit. According to gestational age, the subjects were classified into three groups as follows: group 1: gestational age <35 weeks (n=54); group 2: 35 weeks <= gestational age <37 weeks (n=35); group 3: gestational age >=37 weeks (n=46). Six hours after surfactant was given, there were significantly better blood gas results in group 1 and worse results in groups 2 and 3. Similar oxygenation function parameter results were observed in the three groups. In addition, there was a trend toward an increased rate of repeated surfactant administration with increasing gestational age. For near-term and term infants, the efficacy of surfactant therapy was not as good as it was for preterm infants. The causes of RDS in near-term and term infants might be different from those in preterm infants and should be studied further. PMID- 26550327 TI - Low levels of serum 25-hydroxyvitamin D and risk of metabolic syndrome in China. AB - Recent evidence indicates the potential role of vitamin D in the prevention of Metabolic syndrome (MetSyn). This is an analytical cross sectional study. A total of 3275 subjects were investigated. 25-hydroxyvitamin D(25[OH]D) was detected by electrochemiluminescence immunoassay (ECLIA) technology. Metabolic syndrome was defined according to the definition of International Diabetes Federation (IDF). Among the participants, the prevalence of the MetSyn was 6.0%. The prevalence of vitamin D deficiency and insufficiency was 50.1% and 25.0% respectively. Subjects with MetSyn presented with significantly lower 25(OH)Vit D serum levels compared with non-MetSyn group. The results shows that vitamin D deficiency is common in Chinese adults, and subjects with lower serum 25(OH)D have a higher risk of the MetSyn. The cut-off value of serum 25(OH)D that reflected MetSyn in Chinese adluts was 15.655 ng/mL. PMID- 26550328 TI - Treatment of tibial eminence fractures with arthroscopic suture fixation technique: a retrospective study. AB - AIMS: The present study aims to investigate the clinical outcomes of arthroscopic suture fixation in treating tibial eminence fracture with a retrospective study design of two years' follow-up. METHODS: A total of 33 patients with imaging evidence of tibial eminence avulsion fractures who underwent arthroscopic surgery between 2008 and 2012 were included in this study. The inclusion criteria for the study were a displaced tibial eminence avulsion fracture and anterior knee instability of grade II or higher inskeletally mature patients. These patients were treated with arthroscopic suture fixation and followed with a mean period of 24 months. Anteroposterior and lateral radiographs were obtained 3 months postoperatively to assess fracture healing. At 24 months after surgery, all patients were evaluated by an independent orthopaedic professor with clinical examination like anteroposterior laxity (Lachman-Noulis and anterior drawer tests) and Rolimeter knee tester (Aircast, Vista, CA). Knee range of motion was evaluated actively and passively with a goniometer. Knee function was evaluated by the Lysholm and International Knee Documentation Committee (IKDC) scores. Knee radiographs in standing anteroposterior, standing lateral, and Merchant views were examined for alignment, joint space narrowing, and degenerative knee changes. RESULTS: No major complication like infection, deep venous thrombosis, or neurovascular deficit happened peri-operatively. At the final follow-up, there were no symptoms of instability and no clinical signs of ACL deficiency. Radiographs showed that all fractures healed 3 months post-operative, but at the last follow-up, there was one person with degenerative changes like joint space narrowing in radiographs. Anterior translation of the tibia was 0.47 mm on average (0 to 2.5 mm) compared with the uninjured side. Range-of-motion measurement showed a mean extension deficit of 1.5 degrees (0 degrees to 5 degrees ) and a mean flexion deficit of 2.7 degrees (0 degrees to 10 degrees ) compared with the unaffected side. The mean Lysholm score was 96 (85 to 100), and the mean IKDC score was 94 (80 to 100). Overall, the IKDC grade was A (normal) in 24 patients (58%), B (nearly normal) in 8 patients (33%), and C (abnormal) in 1 patient (8%). CONCLUSION: The present study demonstrated tibial eminence fractures in adults can be effectively treated with arthroscopic suture fixation. PMID- 26550329 TI - Fertility-conservation combined therapy with hysteroscopic resection and oral progesterone for local early stage endometrial carcinoma in young women. AB - OBJECTS: This paper explored the suitable population for the combined therapy of hysteroscopic resection and oral megestrol acetate (MA) to treat local stage I endometrial cancer. Therapeutic effectiveness, safety, as well as pregnancy rate and relapse rate after treatment were also examined. The aim was to provide guidance for the treating similar cases in the future. METHODS: This perspective study analyzed the clinical data of early stage endometrial cancer patients who have received combined therapy of hysteroscopic resection of local endometrial lesion and oral administration of MA at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai. RESULTS: A total of six patients met the entry criteria and were enrolled into the trial. All of them achieved a pathologic complete response to hysteroscopic resection of local lesion combined with oral administration of MA for 3 months to 6 months. Among the patients, three became pregnant after natural conception and had healthy infants delivered vaginally at full term without assistance. No relapse occurred in the follow-up study over 48.5 months on average. CONCLUSIONS: In early-stage endometrial cancer, young patients who had already given birth demand may receive hysteroscopic resection combined with oral administration of MA as conservative treatment. The patients can consider natural conception after complete remission, but a close follow-up was crucial to ensuring that the patients were free from other factors affecting childbearing ability. PMID- 26550330 TI - Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats? AB - Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-alpha, IL-1beta, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-alpha and IL-1beta (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue. PMID- 26550331 TI - Protective effects against hepatic ischemia-reperfusion injury after rat orthotopic liver transplantation because of BCL-2 overexpression. AB - This study aims to investigate the protective effects and mechanism of recombinant adenovirus Ad.VSG-hBCL-2 towards ischemia/reperfusion injury in rat liver graft. Recombinant adenovirus Ad.VSG-hBCL-2 was injected into the donor rat liver of the experiment group through the portal vein, the laparotomy was performed for liver 36 h later, and the liver was save in lactated Ringer's solution at 4 degrees C for 4 h, "two-cuff method" was used to perform the orthotopic liver transplantation. The bile secretion situations of two groups were observed 6 h after the portal vein reflow; the recipient rats were killed to detect the plasma levels of AST, ALT and LDH. And the expressions of Bcl-2 and TNF-alpha in liver tissue, and TUNEL assay was used to detect the apoptosis of liver tissue cells, electron microscopy was used to observe the changes of subcellular structures of liver tissue. 6 h after the surgery, the immunohistochemistry and Western Blot test showed that the Bcl-2 expression in the liver of the experiment group significantly increased than the control group, the bile secretion increased, the levels of AST, ALT and LDH were significantly lower, and the TNF-alpha expression increased significantly. The changes of cellular morphology of the experiment group were milder, and the apoptotic index was significantly lower than the control group. The portal vein-transfected recombinant adenovirus Ad.VSG-hBCL-2 could be effectively expressed in rat liver, and the high expressed Bcl-2 could reduce the ischemia/reperfusion injury in the transplanted liver. PMID- 26550332 TI - Comparison of bupivacaine and parecoxib for postoperative pain relief after laparoscopic cholecystectomy: a randomized controlled trial. AB - BACKGROUND: Pain is the most common complaint of patients on the first day after laparoscopic cholecystectomy (LC). The aim of this study was to compare the efficacy of local anesthesia with bupivacaine and intravenous parecoxib on postoperative abdominal pain relief up to 24 h after surgery. METHODS: One hundred and eighty patients who underwent LC were randomized to one of three groups with sixty patients each: Group A received 50 mg 0.5% bupivacaine subcutaneously at trocar sites before incision closure; Group B received intravenous parecoxib (40 mg) after entering the recovery room; Group C did not receive postoperative analgesia unless needed and was served as control. The postoperative pain at 1, 2, 4, 8, 12, and 24 h after the operation was assessed using a visual analog scale (VAS). Secondary outcomes, including intraoperative and postoperative complications, the incidence of shoulder pain, pethidine requirements, postoperative nausea and vomiting, and hospital stay were also recorded. RESULTS: At 1, 2, and 4 hours after surgery, VAS pain scores were significantly lower in group A and B compared with group C (P < 0.05 for all). There was no significant difference among the three groups at 8, 12, and 24 hours after the procedure (P > 0.05 for all). A repeated-measures ANOVA analysis revealed that VAS pain scores over the first 24 hours after LC were significantly lower in group A and B compared with group C (P = 0.014 and P = 0.029 for between group comparison, respectively). Furthermore, the percentage of patients requiring postoperative rescue analgesics was significantly higher in group C as compared with group A and group B (P = 0.018). CONCLUSION: Local anesthesia with bupivacaine and intravenous parecoxib are both effective at decreasing postoperative pain and pethidine requirements after LC. PMID- 26550333 TI - Different regulation of Toll-like receptor 4 expression on blood CD14(+) monocytes by simvastatin in patients with sepsis and severe sepsis. AB - We have demonstrated that regulation of Toll-like receptor 4 (TLR4) surface expression levels on blood CD14(+) monocytes by simvastatin treatment in patient with sepsis is different from that in patients with severe sepsis. In patients with sepsis simvastatin treatment statistically significantly decreased TLR4 surface expression level on blood CD14(+) monocytes, while in patients with severe sepsis simvastatin treatment had no significant influence on TLR4 surface expression level on blood CD14(+) monocytes. The changes of plasma interleukin-6 (IL-6) induced by simvastatin in patients with sepsis and severe sepsis were similar with that of TLR4. Our results indicated simvastatin treatment differently influenced inflammation process in patients with sepsis and severe sepsis, which might partially explain the discrepancy, presented by previous trials, about the therapeutic effects of simvastatin treatment in patients with sepsis and severe sepsis. PMID- 26550334 TI - Diffusion-weighted magnetic resonance imaging in predicting the radiosensitivity of cervical cancer. AB - This study investigates the application value of diffusion-weighted magnetic resonance imaging in predicting cervical cancer radiosensitivity. Twenty-five patients who were newly diagnosed as cervical cancer and accepted simple radiotherapy were included in this study. Before external irradiation, 20 GY and at the end of irradiation, routine 1.5 T MRI and diffusion-weighted magnetic resonance imaging scanning were carried. Apparent diffusion coefficient (ADC) value of primary tumor was measured. Its correlation with tumor regression rate was analyzed. ADC values of before irradiation, 20 GY and at the end of irradiation was (0.93 +/- 0.14) * 10(-3) mm(2)/s, (1.25 +/- 0.17) * 10(-3) mm(2)/s and (1.55 +/- 0.13) * 10(-3) mm(2)/s, respectively. There were statistical significant differences (P< 0.01). D-value of ADC values between before and 20 GY external irradiation was (0.33 +/- 0.16) mm(2)/s. The tumor volume before and at the end of external irradiation were (37.48 +/- 26.83) cm(3) and (4.41 +/- 3.72) cm(3) respectively, with tumor regression rate of before and after external irradiation of (0.86 +/- 0.11). ADC values of before irradiation, 20 GY and at the end of irradiation did not correlate with tumor regression rate. D-value of ADC values between before and 20 GY external irradiation positively correlated with tumor regression rate (r = 0.423, P = 0.035). ADC value of cervical cancer increased after radiotherapy and early changes of ADC value was positively correlated with tumor regression rate, thus, ADC value could be used as a potential prediction factor for cervical cancer radiosensitivity. PMID- 26550335 TI - Effect of nucleoprotein factor-kB (NF-kappaB) in endothelial cells during high blood flow-associated pulmonary vascular remodeling on vasoactive substances adrenomedullin and prostacyclin. AB - The aim of this study was to investigate the role of nucleoprotein factor-kB (NF kappaB) on the production and secretion of vasoactive substances adrenomedullin (ADM) and prostacyclin (PGI2) by endothelial cells in a high blood flow, pulmonary hypertension in vivo model. Fifty male Wistar rats were randomly divided into four groups: 15 rats received shunt surgery (Tn group); 15 rats received shunt surgery + NF-kappaB inhibitor [pyrrolidine dithiocarbamate (PDTC)] (Ti group); 10 rats received sham surgery (Co group); and 10 rats were negative controls (Cn group). A left to right shunt pulmonary hypertension model was established in groups Tn and Ti. Rats in the Ti group received an intraperitoneal injection of PDTC (120 mg/kg.d) one hour before the operation for 2 weeks, and rats in the Co group were processed in the same fashion as that of the experimental groups, except that they did not undergo surgery. After 12 weeks, pulmonary artery systolic pressure was measured by cardiac catheterization, pulmonary arterial endothelial cells were isolated, and NF-kappaB, ADM and PGI2 protein expressions were measured in the endothelium using immunohistochemistry. ADM and PGI2 expressions were significantly lower in the Tn group relative to those of the Cn group (P<0.01) but no difference in the Ti group (P>0.05). Expressions in the Co and Cn groups were not significantly different (P>0.05). Heightened NF-kappaB activity in pulmonary arterial endothelial cells during high blood flow can suppress the synthesis and secretion of ADM and PGI2, potentially leading to vascular remodeling and pulmonary hypertension. PMID- 26550336 TI - Can red cell distribution width be a marker of disease activity in ulcerative colitis? AB - AIM: The current study aimed to investigate the association between disease activity and red cell distribution width (RDW) levels in ulcerative colitis and to determine whether RDW can be used as a marker of disease activity in non anemic ulcerative colitis. METHODS: The RDW levels of 310 ulcerative colitis patients who underwent colonoscopy were analyzed retrospectively. The patients were divided into two groups (active disease and remission) according to the endoscopic activity index. In addition, the accuracy of RDW in determining disease activity in non-anemic patients was assessed. The efficacy of RDW in determining disease activity was compared to that of white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate. RESULTS: Two hundred and six (66.5%) patients had active disease, and 104 (33.5%) were in remission. The mean RDW levels in patients with active ulcerative colitis and in those in remission were 16.8+/-2.9 and 15.5+/-1.4, respectively (P<0.001). Ninety six (46.6%) patients in the active disease group and 89 (85.6%) in the remission group were non-anemic, and their respective RDW levels were 15.4+/-1.2 and 15.3+/ 1.1 (P=0.267). The sensitivity and specificity of RDW in determining inflammation were 41% and 91%, respectively (AUC 0.65, P<0.001). CONCLUSIONS: This study demonstrated that RDW can be used as a marker for disease activity in ulcerative colitis, but it did not have the same efficacy in the non-anemic group. PMID- 26550337 TI - Clinical comparison of Zero-profile interbody fusion device and anterior cervical plate interbody fusion in treating cervical spondylosis. AB - OBJECTIVE: the aim of the study was to compare the clinical effect of Zero profile interbody fusion device (Zero-P) with anterior cervical plate interbody fusion system (PCB) in treating cervical spondylosis. METHODS: a total of 98 patients with cervical spondylosis (110 segments) in February 2011 to January 2013 were included in our hospital. All participants were randomly divided into observation group and control group with 49 cases in each group. The observation group was treated with Zero-P, while the control group received PCB treatment. Comparison of the two groups in neurological function score (JOA), pain visual analogue scale (VAS), the neck disability index (NDI), quality of life score (SF 36) and cervical curvature (Cobb angle) change were recorded and analyzed before and after treatment. RESULTS: The observation group was found with 90% excellent and good rate, which was higher than that of the control group (80%). Dysphagia rate in observational group was 16.33% (8/49), which was significantly less than that in control group (46.94%). Operation time and bleeding volume in the observation group was less than those in control group. Postoperative improvements of JOA score, VAS score, and NDI in observational group were also significantly better than that in control group (P<0.05). CONCLUSION: The clinical effect of Zero-P and PCB for the treatment of cervical spondylosis was quite fair, but Zero-P showed a better therapeutic effect with improvement of life quality. PMID- 26550338 TI - Drug-resistant gene of blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 in Acinetobacter baumannii. AB - We distinguished the four alleles of OXA subgroups from 339 strains of Acinetobacter baumannii using Polymerase Chain Reaction, and investigated distributions of OXA subgroups in clinical isolated strains. A total of 196 Acinetobacter baumannii were isolated from the Central Hospital of Zhumadian between 2010 and 2014. Amplification of OXA genes, blaOXA-23, blaOXA-24, blaOXA 51 and blaOXA-58, were performed by PCR. Patients with Acinetobacter baumannii were selected from ICU, pneumology, emergency and cerebral surgery, accounting for 33.67%, 17.86%, 16.33% and 32.14%, respectively. Most strains showed resistance to different classes of agents, especially in ceftazidime, piperacillin, cefepime, nitrofurantoin and ertapenem. Multiplex PCR results showed, out of the 339 isolated strains, 164 (48.38%) were blaOXA-51, 157 (46.31%) were blaOXA-23, 18 (5.31%) were blaOXA-58, and no strain for blaOXA-24. 143 (47.67%) strains of blaOXA-51, 143 (47.67%) strains of blaOXA-23, and 14 (4.66%) strains of blaOXA-58 showed multidrug-resistant. In conclusion, our study found that OXA-51 and OXA-23 were the main mechanisms of resistant or sensitivity to carbapenems. PMID- 26550339 TI - Magnesium sulfate inhibits sufentanil-induced cough during anesthetic induction. AB - Sufentanil-induced cough is a common phenomenon during the induction of anesthesia. This double-blind, randomized, and placebo-controlled study was designed to investigate the effects of prophylactic magnesium sulfate (MgSO4) on the incidence and severity of sufentanil-induced cough. A total of 165 patients who were scheduled for elective surgery under general anesthesia were allocated into three groups (I, II, and III; n = 55 each) that were injected with either 50 ml of normal saline, 30 or 50 mg/kg of MgSO4 (diluted with normal saline into 50 ml). One minute following the injection, all patients were injected with 1.0 MUg/kg of sufentanil within 5 s. The incidence and severity of cough were recorded 30 s after the sufentanil injection. The hemodynamic parameters and plasma magnesium concentration of the patients were also noted. Three patients dropped out the study due to an obvious burning sensation during the injection of 50 mg/kg of MgSO4. Although the injection of 50 mg/kg of MgSO4 increased the plasma magnesium level, the increase remained within the therapeutic range (2-4 mmol/L). The incidence of cough was much higher in group I than in groups II and III (47.1% vs. 16.4% and 7.6%, respectively, P < 0.05). Compared with group I, group III had the lowest incidence of mild cough and both groups II and III had lower incidence of moderate and severe cough (P < 0.05). There were no differences in the hemodynamic data at three timepoints among the three groups. In conclusion, sufentanil-induced cough may be suppressed effectively and safely by prophylactic use of 30 mg/kg of MgSO4 during anesthetic induction. PMID- 26550340 TI - Association study between SMPD1 p.L302P and sporadic Parkinson's disease in ethnic Chinese population. AB - PURPOSE: The protein encoded by sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) is a lysosomal acid sphingomyelinase. While there are increasing evidences to suggest that lysosomal enzyme defects and Parkinson's disease (PD) have strong associations, and recently, SMPD1 p.L302P (c.T911C, NM_000543) was found to be a risk factor for PD in Ashkenazi Jewish ancestry population, we try to investigate the possible association between SMPD1 p.L302P and sporadic PD in ethnic Chinese population. METHODS: 455 sporadic PD and 476 health controls were included in our study. SMPD1 p.L302P (c.T911C) was genotyped by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and the results were confirmed by Sanger sequencing. RESULTS: Our results showed that none of 455 sporadic PD and 476 health controls carried p.L302P. All of the 931 subjects' genotypes were wild type TT. Our data indicated that in an ethnic Chinese population, p.L302P did not appear to be enriched in sporadic PD, and p.L302P may not be a risk factor for Chinese sporadic PD. And combine our data with the results from previous studies, we found that all of the 2,268 participants of Chinese population carrying no p.L302P. CONCLUSIONS: We could make a conclusion that p.L302P may not be common events for Chinese population. Sequencing of SMPD1 gene to find additional novel rare variants in the SMPD1 gene in diverse populations is needed. PMID- 26550341 TI - A meta-analysis of XPD/ERCC2 Lys751Gln polymorphism and melanoma susceptibility. AB - We performed a comprehensive meta-analysis to determine the association between XPD/ERCC2 Lys751Gln polymorphism and melanoma susceptibility. Based on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between XPD/ERCC2 Lys751Gln polymorphism and melanoma risk. A total of 5,961 cases and 8,669 controls in studies were included in this meta-analysis. All studies were conducted in Caucasian populations. Allele model (Lys vs. Gln: P = 0.53; OR = 0.98, 95% CI = 0.91-1.05), and homozygous model (Lys/ Lys vs. Gln/Gln: P = 0.32; OR = 0.93, 95% CI = 0.81 to 1.07) did not show increased risk of developing melanoma. Similarly, dominant model (Lys/ Lys+Lys/Gln vs. Gln/Gln: P = 0.18; OR = 0.93, 95% CI = 0.83 to 1.03) and recessive model (Lys/ Lys vs. Lys/Gln+Gln/Gln: P = 0.73; OR = 0.98, 95% CI = 0.88 to 1.09) failed to show increased risk of developing melanoma. Our pooled data suggest that there was no evidence for a major role of XPD/ERCC2 Lys751Gln polymorphism in the pathogenesis of melanoma among Caucasian populations. PMID- 26550342 TI - Klotho protein lowered in senile patients with brady sinus arrhythmia. AB - OBJECTIVE: To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. METHODS: 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. RESULTS: The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. CONCLUSION: The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node. PMID- 26550343 TI - Polymorphisms in checkpoint kinase 2 may contribute to lymph node metastasis from esophageal cancer. AB - Esophageal cancer, which is commonly accompanied by lymph node metastasis, is among the deadliest of cancers and carries a grim prognosis. We investigated the association between genetic variation in checkpoint kinase 2 (CHEK2), which has been linked to metastasis in other cancers, and the risk of developing lymph node metastasis from esophageal cancer. CHEK2-122 G/C genotypes were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in 296 subjects with esophageal cancer (67 cases with and 229 cases without lymph node metastasis). The associations between CHEK2 genotypes and the risk of lymph node metastasis from esophageal cancer were estimated by computing odds ratios (OR) and their 95% confidence intervals (CI). The CHEK2 GG, GC, and CC genotype frequencies in patients with and without lymph node metastasis were 47.8%, 40.3%, and 11.9% and 31.0%, 50.7%, and 18.3% respectively, and were statistically significant (chi(2) =6.591, P=0.037). Logistic regression analyses revealed that the CHEK2-122 GC genotype significantly reduced the risk of lymph node metastasis (adjusted OR=0.54, 95% CI=0.29-0.93, P=0.028) compared to the GG genotype. Subsequently, we propose that the CHEK2-122 G/C polymorphism may play a protective role in preventing lymph node metastasis from esophageal cancer, and may also provide insight toward determining patient prognosis without the use of surgery. PMID- 26550344 TI - Clinical significance of C-reactive protein levels in the determination of pathological type of acute appendicitis. AB - OBJECTIVE: To investigate the significance of C-reactive protein (CRP) in the discrimination of acute appendicitis pathology and its guiding role in the timing of surgery. METHODS: 307 patients in our hospital from July 2012 to December 2013 were selected, who received appendectomy and simultaneous detections of WBC, neutrophil percentage and CRP; and Logistic regression analysis and Roc analysis of these indicators were conducted; Roc curve was drawn. RESULTS: Logistic regression analysis showed that the proportion of neutrophils and CRP were the risk factors to determine gangrenous appendicitis, but the box chart and Roc curves showed that C-reactive protein was superior to neutrophil classification in determining gangrenous appendicitis (areas under the curve were 0.882 and 0.667 respectively), and the best diagnostic cutoff value was 44.42 mg/L (sensitivity 73.1%, specificity 89.5%). CONCLUSION: C-reactive protein levels can help distinguish pathological types of acute appendicitis, which can be used as a reference index for surgery determination. PMID- 26550345 TI - Mild cognitive impairment risk factor survey of the Xinjiang Uyghur and Han elderly. AB - To understand risk factors of the Xinjiang Uyghur, Han two ethnic elderly with mild cognitive impairment (mild cognitive impairment, MCI), and provide evidence for in-depth study of the causes and prevention of MCI. The MCI epidemiological survey was based on Xinjiang Uyghur and Han residents with 60 years of age or older. The total number of participants is 5398, including 3931 Uyghur residents, and 1467 Han residents. There are 456 participants with MMSE score 2 points above the demarcation points, excluded from the survey for dementia, cerebrovascular disease and other central nervous system disorders, according to case-control study method of random selection in epidemiological survey. In accordance with the clinical diagnostic criteria of MCI, which is from Disorder Diagnostic and Statistical Manual (the revised version of the fourth edition (DSM-IV) from of the American Psychiatric Association, there are 305 cases of MCI, including 159 cases of Han, 146 cases of Uyghur. In the Han groups: univariate analysis showed a correlation (P < 0.05) between sex, age, blood pressure, triglyceride (TG), low density lipoprotein (LDL-ch) and MCI. Multivariate Logistic regression analysis showed: age, hypertension, TG, LDL-ch (increased) may increase the risk of MCI (OR values were: 1.115, 1.981, 1.315, 1.495, with P < 0.05). In the Uyghur groups: univariate analysis showed a correlation (P < 0.05) between age, gender, hypertension, abnormal glucose metabolism, TG, TC, LDL-ch and MCI. Multivariate Logistic regression analysis showed: age, hypertension, abnormal glucose metabolism, TG, TC, LDL-ch (increased), women have a higher risk of MCI (OR values were: 1.063, 2.145, 2.879, 2.078, 1.429, 1.485, 0.462, P < 0.05). Age, hypertension, TG and LDL-ch are risk factors of MCI for Han population, while age, hypertension, abnormal glucose metabolism, TG, TC and LDL-ch are risk factors of MCI for Uyghur population. PMID- 26550346 TI - The prevalence of erectile dysfunction among subjects with late-onset hypogonadism: a population-based study in China. AB - INTRODUCTION: The concurrence of chronic diseases and some well-defined risk factors significantly impacts the prevalence of erectile dysfunction (ED). AIM: To determine whether late-onset hypogonadism (LOH) impacts the prevalence of ED using investigation reproductive health data of middle-aged and aging males in China. METHODS: The reproductive health status of 1498 males, aged 40-69 years, was evaluated using questionnaires of LOH based on the Androgen Deficiency in Aging Males (ADAM) and Aging Male Symptoms scale (AMS), as well as the International Index of Erectile Function-5 (IIEF-5) assessment. The 10th percentile of serum total testosterone (TT) and calculated free testosterone (cFT) levels of controls were set as cut-off levels of AD. The main outcome measures were used to assess the prevalence of LOH and ED according to different subject characteristics. RESULTS: Of the 1472 subjects who completed the questionnaires who supplied hormone measurements, the prevalence of self-reported ED and identified by the IIEF-5 assessment were 11.28% and 77.85%, respectively. The IIEF-5 assessment revealed a prevalence of ED of 55.34%, 88.20%, and 91.77%, respectively, among those aged 40-49, 50-59, and 60-69 years. AD rates of ED subjects were 13.73% and 40.69% according to the TT and cFT cut-off levels. The prevalence of ED among subjects positive for LOH (ADAM+ and AMS+) were 88.81% and 95.80%, respectively. The prevalence of ED among the AD subjects (TT and cFT cut off levels) with LOH (ADAM+ and AMS+) were 86.67%/81.82%. And the prevalence of ED among clinical LOH subjects (ADAM+ and AMS+) were 89.51%/98.48%. CONCLUSIONS: We found that middle-aged and aging Chinese males were at a relatively high risk of ED. The prevalence of ED among subjects with LOH symptoms was greater than in all recruited subjects. The effect of LOH on the prevalence of ED far outweighed the risk of decreased testosterone levels. PMID- 26550347 TI - Genetic polymorphisms in the PDZK1 gene and susceptibility to gout in male Han Chinese: a case-control study. AB - PDZK1 acts as a scaffolding protein for a large variety of transporter and regulatory proteins, and has been identified in the kidney. The PDZK1 locus has been determined to be associated with the serum urate concentration. However, the evidence supporting this protein's association with gout is equivocal. In the current study, we investigated the association between two single nucleotide polymorphisms (SNPs) (rs12129861 and rs1967017) in the PDZK1 gene with gout in a male Chinese Han population. A total of 824 subjects were enrolled in this case control study (400 gout cases and 424 controls). PDZK1 genotyping was carried out by polymerase chain reaction (PCR) and ligase detection reaction (LDR) assays methods. The relationships were evaluated using the pooled odds ratios (ORs) and their 95 % confidence intervals (CI). The results of our case-control study demonstrated that the gout and control groups exhibited significant differences in the distribution of genotypes at rs12129861 (OR = 0.727, P = 0.015) and rs1967017 (OR = 0.705, P = 0.016), suggesting that PDZK1 genetic polymorphisms were associated with increased risks of gout in male Han Chinese. However, there were no differences in the distribution of genotypes at rs12129861 (odds ratio (OR) = 0.744, P > 0.05) and rs1967017 (OR = 0.706, P > 0.05) in patients with gout with kidney stones and without kidney stones. PMID- 26550348 TI - Effect of cigarette smoking and alcohol consumption on disease activity and physical functioning in ankylosing spondylitis: a cross-sectional study. AB - The effect of cigarette smoking and alcohol consumption on the disease activity and physical functioning in ankylosing spondylitis (AS) is currently understated. Present study aims to investigate the relationship between them. A total of 425 patients with AS were recruited in the study and their smoking and drinking habit were investigated with a semi-quantitative food frequency questionnaire. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Metrology Index (BASMI) were evaluated. Parameters including fingertip-to-floor distance, overall assessment of health, nocturnal pain, total back pain and morning stiffness were analyzed as well. Blood erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined. For 118 (27.8%) AS patients with smoking habit, the scorings of BASDAI, BASFI, BASMI and other physical parameters (including fingertip-to-floor, overall assessment of health, nocturnal pain and total back pain) were higher than those in patients without smoking. 101 (23.8%) AS patients with alcohol consumption demonstrated significantly higher scores in BASMI (P < 0.05). In hierarchical multiple regression analysis, the cigarette smoking and alcohol consumption variables contributed to the variance in BASDAI scores, adding an additional 1.6% to the overall R-square, resulting in a final R-square of 5.1%. Smoking has a negative effect on disease activity of patients with AS and the patients' physical functioning. Alcohol consumption would aggravate the overall physical functioning of AS patient. The results indicated the potential benefit of quitting smoking and drinking for AS patients. PMID- 26550349 TI - Serum soluble major histocompatibility complex class I-related chain A/B expression in patients with alcoholic liver disease in Hainan Li community. AB - BACKGROUND/AIMS: To study the expression and clinical significance of serum soluble major histocompatibility complex class I-related chain A/B (sMICA/B), and its correlation with percentage of CD4(+), CD8(+), and NK cells, Liver fibrosis screening test, and liver enzymes in alcoholic liver disease (ALD). METHODS: Hainan Li ALD patients (n = 141) and healthy Li subjects (n = 100) were enrolled for the study. Liver enzymes were measured using automatic biochemical analyzer and Liver fibrosis screening test was used to study the correlation. In addition, sMICA/B expression in serum and percentage of CD4(+), CD8(+), and NK cells were determined using ELISA and flow cytometry respectively. RESULTS: Liver fibrosis screening test results and liver enzymes concentration were significantly higher (both P < 0.01), whereas the expression of sMICA and sMICB was significantly indifferent (P > 0.01) between ALD patients and healthy controls. However, percentage of CD4(+), CD8(+), and NK cells were statistically lower in ALD patients than in healthy controls. The Kendall's tau-b correlation coefficient for sMICA and sMICB/sMICA and LV was 0.561 and 0.120 respectively (P < 0.01). Pearson correlation coefficient of sMICA with the percentage of CD4(+), CD8(+)%, and NK cells was -0.587, -0.525, and -0.232 respectively, whereas the coefficient of sMICB was -0.590, -0.554, and -0.292 respectively (P < 0.01). CONCLUSION: 1. Liver fibrosis screening test is an excellent non-invasive approach for the diagnosis of hepatic fibrosis and shows significant correlation with liver enzymes. 2. sMICA and sMICB failed to assess the degree of hepatic fibrosis. 3. Decreased percentage of CD4(+), CD8(+), and NK cells were attributed as one of the risk factors for ALD. PMID- 26550350 TI - Early enteral nutrition in combination with parenteral nutrition in elderly patients after surgery due to gastrointestinal cancer. AB - OBJECTIVE: To evaluate the therapeutic effects of nutritional support via different routes in elderly patients after surgery for gastrointestinal (GI) cancer. METHODS: 105 patients with GI cancer were randomly divided into early enteral nutrition (EEN) group (n = 35), total parenteral nutrition (TPN) group (n = 35) and EN+PN group (n = 35). RESULTS: The nutrition status and immunity were significantly compromised in all patients, while the liver function was improved at 3 days after surgery as compared to those before surgery. At 7 days after surgery, they returned to preoperative level. The nutrition status was comparable among 3 groups at 3 and 7 days after surgery (P > 0.05). ALT, AST, ALP and GGT in TNP group were significantly higher than those in EEN group and EN+PN group (P < 0.05), whereas there was no significant difference in the liver function between EEN group and EN+PN group (P > 0.05). The CD3+ cells, CD4+ cells and CD4/CD8 in EEN group and EN+PN group were significantly higher than those in TPN group (P < 0.05), but significant difference was not observed between EEN group and EN+PN group (P > 0.05). The NK cells in EN+PN group were significantly higher than in TPN group (P < 0.01). The incidence of diarrhea in EEN group was significantly higher than in TPN group and EN+PN group (P < 0.05). CONCLUSION: EN+PN is superior to EEN alone and TPN alone in the old patients with GI cancer in reducing the postoperative complications, improving the immunity and decreasing the hospital stay. PMID- 26550351 TI - Acute hypotension after total knee arthroplasty and its nursing strategy. AB - OBJECTIVE: To determine the factors affecting postoperative acute hypotension after total knee arthroplasty (TKA) and provide a basis for guiding the clinical prevention. METHODS: Between May 2001 and May 2013, a total of 495 patients undergoing routine TKA were analyzed retrospectively. Independent risk factors related to postoperative acute hypotension after TKA were determined by univariate and multivariate analysis. RESULTS: Of the 495 patients undergoing TKA, 61 (12.32%) developed postoperative acute hypotension after surgery. Univariate analysis showed that preoperative Neu, time of surgery, time of anesthesia, pressure of tourniquet, time of using tourniquet, preoperative hypertension, age and type of surgery were significant influencing factors, whereas by multivariate analysis, only age, pressure of tourniquet and type of surgery were significant influencing factors. CONCLUSION: Factors those were associated with a significantly increased postoperative acute hypotension after TKA included age, pressure of tourniquet and type of surgery. Achieving a good preoperative and postoperative evaluation and monitoring vital signs and disease change contribute to the detection, intervention and salvage for the acute hypotension. PMID- 26550352 TI - A novel insight in exploring the positive end expiratory pressure for sustained ventilation after lung recruitment in a porcine model of acute respiratory distress syndrome. AB - The aim of the present study was to explore a novel insight to determine the positive end expiratory pressure (PEEP) for sustained ventilation after lung recruitment in an acute respiratory distress syndrome (ARDS) model. Continuous infusion of oleic acid was performed to establish a ARDS model. Pressure control ventilation (PCV) was applied for lung recruitment with PEEP of 20 cm H2O. After lung recruitment, maneuver was changed to volume-controlled ventilation and PEEP titration were performed by decreasing PEEP gradually starting from the level of 20 cm H2O. The optimal level of PEEP for sustained ventilation was set as the lowest PEEP until oxygen partial pressure (PaO2) plus carbon dioxide partial pressure (PaCO2) >=400 mmHg. Hemodynamic and respiratory parameters at basal level, ARDS state and different levels of PEEP around the optimal PEEP were recorded. The defined optimal PEEP was 13.14 +/- 1.35 cm H2O. Respiratory parameters including intrapulmonary shunt (Qs/Qt) and arterial oxygen saturation (SaO2) were significantly improved by various levels of PEEP for sustained ventilation after lung recruitment (P<0.05). Static compliance (Cst) and dynamic compliance (Cdyn) were also significantly increased after application of different levels of PEEP ventilation after lung recruitment (P<0.05). There was no significant statistic difference on most hemodynamic parameters (P>0.05) between various levels of PEEP. The application of different PEEP levels around the defined optimal PEEP had an obvious improvement on respiratory mechanics and gas exchange for collapsed lung tissue without influencing the hemodynamics. PMID- 26550353 TI - Infective endocarditis: a tertiary referral centre experience from Turkey. AB - INTRODUCTION: We aimed to define the current characteristics of infective endocarditis (IE) in a part of Turkey. METHODS: All patients who were hospitalized in our hospital with a diagnosis of IE between 2009 and 2014 were included in the study. Data were collected from archives records of all patients. Modified Duke criteria were used for diagnosis. RESULTS: There were 85 IE cases during the study period. The mean age of patients was 52 years. Fourty eight of patients were males. Native valves involved in 47%, prostetic valves involved in 40% and pacemaker or ICD lead IE in 13% of patients. Mitral valve was the most common site of vegetationb (38%). The most common valvular pathology was mitral regurgitation. The most common predisposing factor was prosthetic valve disease (40%). Positive culture rate was 68%. Staphylococci were the most frequent causative microorganisms isolated (27%) followed by Streptococcus spp. (11%). In hospital mortality rate was 36%. CONCLUSION: In Turkey, IE occurs in relatively young patients. In high developed part of Turkey, prosthetic and dejenerative valve disease is taking the place of rheumatic valve disease as a predisposing factor. Surgery is an important factor for preventing mortality. PMID- 26550354 TI - Diagnosis of children's attention deficit hyperactivity disorder (ADHD) and its association with cytomegalovirus infection with ADHD: a historical review. AB - As the most common mental disorder identified in children and teenagers, attention deficit hyperactivity disorder (ADHD) affects millions of children and their families, making it a critical health issue worldwide. This article reviewed the historical opinions about the diagnosis of ADHD and defined different subtypes of this disorder. It also summarized the current diagnostic criteria and available medications. After re-visiting the etiology of ADHD in the sense of both genetic and environment factors, it was further hypothesized that viral infection might be involved in ADHD pathogenesis. Human cytomegalovirus (HCMV) infection may be associated with ADHD, although both clinical observations and animal studies need to be performed for validation. PMID- 26550355 TI - Application of ultrasound-guided subcostal transversus abdominis plane block in gastric cancer patients undergoing open gastrectomy. AB - BACKGROUND: To observe intraoperative and postoperative analgesic effect of ultrasound-guided subcostal transversus abdominis plane (TAP) block in gastric cancer patients undergoing open gastrectomy. MATERIAL AND METHODS: Forty patients with gastric cancer underwent open gastrectomy were randomly assigned into groups R and S. All patients received ultrasound-guided subcostal bilateral TAP under general anesthesia, and then were injected with 40 ml of 0.375% ropivacaine (group R) or equivalent amount of normal saline (group S). The surgery was performed in 30 min following the blocking. Intraoperatively, BIS value was maintained between 45 and 65. Patient-controlled intravenous analgesia pump was properly connected after the operation. Intraoperative changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were observed and the dosage of sufentanil and alternative drugs was closely monitored during the surgery. Visual analogue scale (VAS) scores and related surgical complications were recorded at 2, 4, 6, 12, 24 and 48 h following the operation. RESULTS: The SBP, DBP and HR changes in the group R were significantly decreased compared with those in the group S (all P<0.01). In both groups, desirable analgesic effect was obtained. The VAS scores at postoperative 2, 4, 6 and 12 h after the surgery in the group R were significantly lower than those in the group S (all P<0.05). No TAP puncture-induced adverse reaction was observed in both groups. CONCLUSION: Ultrasound-guided subcostal transversus abdominis plane block has the advantages of accurate localization and high success rate. Clinical application of this technique in open gastrectomy can significantly decrease intraoperative and postoperative dosage of analgesics and exert desirable analgesic effect. PMID- 26550356 TI - Effects of simvastatin and atorvastatin on biochemical and hematological markers in patients with risk of cardiovascular diseases. AB - OBJECTIVE: This study aimed to investigate the effects of simvastatin (SVS) and atorvastatin (AVS) on the biochemical and hematological markers in patients with risk of cardiovascular diseases. METHODS: One hundred and fifty outpatients were enrolled from the Department of Cardiology. Patients were treated with AVS or SVS. The lipids and hematological parameters were measured at baseline and after 4-week treatment, and the risk factors of cardiovascular diseases were recorded. RESULTS: After 4-week treatment, the lipids significantly changed. However, for hematological parameters, only mean platelet volume (MPV) significantly decreased after statins treatment (SVS: t = 68.748, P = 0.000; AVS: t = 39.472, P = 0.000), and the extent of decline was similar between SVS group and AVS group (t = 1.063, P = 0.289). There were no correlations between MPV and lipids. SVS and AVS had comparable effects on the lipid parameters after 4-week treatment, and there were no significant correlations of DeltaMPV with the Deltatotal cholesterol, Deltahigh density lipoprotein-cholesterol, Deltalow density lipoprotein cholesterol, Deltatriglyceride, Deltaapolipoproteint A1, Deltaapolipoproteint B and Deltalipoproteint (a) after treatments (all P > 0.05). CONCLUSION: After statins treatment, the lipids significantly change; only MPV significantly decreases among hematological parameters, but it has no relationship with lipids reduction. The synthetic atorvastatin has similar effects to native simvastatin in the management of patients with risk for cardiovascular diseases. PMID- 26550357 TI - Preoperative risk factors for prolonged postoperative ventilation following thymectomy in myasthenia gravis. AB - Adequate preoperative evaluation and preparation for surgery are required to prevent prolonged mechanical ventilation after thymectomy, and facilitate the recovery of patients with myasthenia gravis (MG). The objective of this study was to identify the preoperative risk factors for extubation failure after thymectomy in patients with MG. METHODS: A retrospective study was conducted on 61 patients with MG who underwent extended thymectomy. Several factors were evaluated including patients' demographic data, preoperative medical therapies, medical history, and comorbidities. Multivariate logistic regression analysis was used to identify the predictors of late extubation after thymectomy for MG. RESULTS: Fourteen patients (22.95%) required breathing support after anesthesia or endotracheal re-intubation within 48 h. Univariate analysis illustrated that the quantitative MG (QMG) grade (odds ratio [OR] = 1.368, P = 0.000), preoperative muscle strength (OR = 0.279, P = 0.000), use of pyridostigmine (OR = 1.011, P = 0.024) and prednisone (OR = 1.059, P = 0.022), preoperative lung function (OR = 4.875, P = 0.016), low preoperative cholinesterase levels (OR = 0.999, P = 0.014), impaired preoperative swallowing muscle activity (OR = 7.619, P = 0.003), and positivity for acetylcholine receptor antibodies (OR = 14.143, P = 0.001) were significant predictors of prolonged postoperative intubation. Multivariate logistic regression analysis revealed that the QMG score (OR = 3.408, P = 0.000) and Myasthenia Gravis Foundation of America (MGFA) classification (OR = 28.683, P = 0.002) were independent risk factors for prolonged postoperative intubation. CONCLUSION: The preoperative MGFA clinical classification and QMG score were independent risk factors for prolonged postoperative intubation in patients with MG. PMID- 26550358 TI - Three pro-nuclei (3PN) incidence factors and clinical outcomes: a retrospective study from the fresh embryo transfer of in vitro fertilization with donor sperm (IVF-D). AB - OBJECTIVES: The aim of this study was to explore the main factors of 3PN incidence and determine whether the presence of 3PN could lead to a worse pregnancy outcome. METHODS: This study included 508 IVF-D (in vitro fertilization with donor sperm) cycles from January 2013 to September 2014. The patients were divided into three groups as follows: group 1 included patients with no 3PN zygotes, group 2 included patients with 1%-25% 3PN zygotes and group 3 included patients with > 25% 3PN zygotes. RESULTS: We observed that more retrieved oocytes and higher HCG day peak E2 value could result in 3PN incidence more easily. When the 3PN zygotes rate was > 25%, the percentages of normal fertilization (68.4% and 66.3% and 46.4%, P < 0.001), day 3 grade I+II embryos (41.2% and 38.6% and 25.8%, P < 0.001), day 3 grade I+II+III embryos (68.7% and 65.2% and 61.4%, P = 0.032) and implantation rates (52.1% and 50.8% and 45.4%, P = 0.026) were significantly lower than that in the other two groups respectively. The pregnancy rate was lower in 3PN > 25% group than that in the other two groups but there was no significant difference (65.2% and 66.7% and 55.6%, P = 0.266). The cleavage (98.3% and 97.2% and 98.2%, P = 0.063) and early abortion (7.1% and 8.0% and 8.6%, P = 0.930) rate were identical among three groups. CONCLUSIONS: More retrieved oocytes and higher HCG day peak E2 value could result in 3PN incidence more easily. Interestingly, normal fertilization rate, day-3 grade I+II embryos rate, day-3 grade I+II+III embryos rate and implantation rate were significantly lower in IVF-D cycles with a 3PN incidence of > 25%. The number of day-3 grade I+II embryos might be a key factor for pregnancy in IVF-D cycles with a 3PN incidence of > 25%. PMID- 26550359 TI - Association between clusterin polymorphisms and esophageal squamous cell carcinoma risk in Han Chinese population. AB - Genetic susceptibility plays an essential role in an individual's risk of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between clusterin (CLU) gene polymorphisms and ESCC risk. We undertook a case-control study to analyze three CLU polymorphisms (gene rs9331888 C>G, rs17466684 A>G and rs1532278 T>C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 642 patients with ESCC and 658 control participants, and performed CLU genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in rs17466684 and rs1532278. However, gene rs9331888 C>G genotype was at increased risk of ESCCs (P=0.037; odds ratio (OR)=1.089, 95% CI: 1.006 1.175). Moreover, rs9331888 G/G genotype ESCCs were more significantly common in patients with tumor size of >5 cm than T allele ESCC and in cases of poor differentiation and lower advanced pathological stage. In conclusion, polymorphism in rs9331888 C>G was observed to be associated with susceptibility of ESCC. Nevertheless, further investigation with a larger sample size is needed to support our results. PMID- 26550360 TI - Early interventional therapy for acute massive pulmonary embolism guided by minimally invasive hemodynamic monitoring. AB - AIM: The aim of this study was to investigate the clinical significance of minimally invasive hemodynamic monitoring in the early catheter-based intervention for acute massive pulmonary embolism (PE). METHODS: A total of 40 cases with acute massive PE were randomized into experimental and control group with 20 cases in each group. In the experimental group, the hemodynamics was monitored via Vigileo/FloTrac system, while echocardiography was used in the control group. Twelve hours after systemic thrombolysis, catheter-based clot fragmentation and local thrombolysis were employed in the experimental group if Vigileo/FloTrac system revealed hemodynamic abnormality. For the control group, the application of catheter was determined by the findings in echocardiography at 24 hours after systemic thrombolysis. RESULTS: A total of 12 cases in the experimental group underwent catheter therapy successfully while 4 cases in the control group received the same treatment. Compared to the control group, 12 hours after catheter intervention the experimental group had higher PaO2/FIO2 and right ventricular ejection fraction (RVEF) but lower pulmonary artery systolic pressure (PASP), indicating the effectiveness of Vigileo/FloTrac monitoring. The 28-day survival rates were identical between the groups although one patent in the control group died. Both the RVEF and PASP were significantly improved in the experimental group in 6 months compared to the control group. CONCLUSIONS: In massive PE, hemodynamic monitoring via Vigileo/FloTrac system might be useful in the decision making for catheter intervention after systemic thrombolysis and might improve the outcomes for patients. PMID- 26550362 TI - Application of transanal ileus tube in acute obstructive left-sided colorectal cancer. AB - OBJECTIVE: The efficacy of transanal ileus tube in acute obstructive left-sided colorectal cancer was discussed. METHOD: A total of 101 cases of acute obstructive left-sided colorectal cancer were divided into two treatment groups. For the experimental group consisting of 52 cases, decompression was performed using transanal ileus tube along with drainage and flushing as preparations for one-stage resection and anastomosis. For the control group consisting of 49 cases, the traditional preoperative preparation including fasting and water deprivation, gastrointestinal (GI) decompression, enema and nutritional therapy was performed. RESULTS: After the ileus tube was indwelled for 3 days, the abdominal circumference, GI decompression amount, and maximum transverse diameter of colon proximal to obstruction changed significantly in the experimental group. The response rate within 24 h and the operation rate of one-stage resection and anastomosis were higher. The incidence and mortality rate after surgery were reduced, the hospitalization time was shorter, and less expenditures were incurred. CONCLUSION: Decompression using transanal ileus tube along with drainage and flushing as preparations for one-stage resection and anastomosis is a safe and effective method for treating acute obstructive left-sided colorectal cancer. PMID- 26550361 TI - Impact of Xuebijing and ulinastatin as assistance for hemoperfusion in treating acute paraquat poisoning. AB - OBJECTIVE: As the effect of Xuebijing as combined treatment in hemoperfusion (HP) toward acute paraquat (PQ) poisoning is not clear. We retrospectively analyzed 119 cases of acute paraquat poisoning in Tianjin first central hospital; the patients were divided into 3 groups based on treatment. Control (group A) patients underwent standard hemoperfusion with conventional treatment, while the experimental groups combined hemoperfusion with Xuebijing (group B) or ulinastatin (group C). Standard biomedical indicators, such as organ dysfunction and mortality were recorded and compiled, both in short (<7 days) and long (7-28 days) terms. Then, the effect of Xuebijing in combination to the standard (HP) treatment was evaluated by direct comparison. The results showed that using either Xuebijing or ulinastatin as additional treatment to standard HP significantly helped the overall outcomes, as evidenced by lower organ dysfunction and mortality. In addition, Xuebijing (group B) yielded a more pronounced improvement compared with ulinastatin (group C) in combination with HP (All P<0.05). Our findings indicated that both Xuebijing and ulinastatin provided positive impacts on HP treatment toward acute paraquat poisoning, with better outcomes observed with Xuebijing, which should be considered for more frequent use in clinical practice. PMID- 26550363 TI - Astragalus on the anti-fatigue effect in hypoxic mice. AB - OBJECTIVE: Astragalus is a traditional Chinese medicine to improve the function of the body. The purpose of this study is to investigate the effect of astragalus on improvement of anti-fatigue capacity in mice under simulated plateau environment. METHODS: Male Kunming mice were randomly divided into the following groups: the control group, astragalus treatment groups in low dosage (LD) (1.0 g/kg.d), mid dosage (MD) (3.0 g/kg.d), and high dosage (HD) (30 g/kg.d). The control group were fed under normoxia environment, and hypoxic mice were fed at a stimulated elevation of 5000 meters. After continuous intragastric administration for 10 days, exhaustive swimming experiment was conducted in the anoxic environment. The swimming time, glucose and lactic acid concentration in blood, glycogen contents in liver, SOD and MDA were determined. RESULTS: Compared with the control group, the swimming time of each astragalus treated group was evidently prolonged (P < 0.05), and the area under the blood lactic acid curve was significantly decreased (P < 0.05). In the high and middle dose of astragalus group, liver glycogen was obviously increased. After exhausted swimming, glycogen contents in blood and SOD were significantly increased, while MDA was evidently reduced (P < 0.05). CONCLUSION: Astragalus can alleviate physical fatigue in mice under simulated plateau environment. It has an obvious anti-fatigue effect and it's worthy of further study. PMID- 26550364 TI - Therapeutic effects and complications of simplified pericardial devascularization for patients with portal hypertension. AB - OBJECTIVES: To evaluate the therapeutic effects and complications of simplified pericardial devascularization for patients with portal hypertension. METHODS: By means of prospective study, 212 patients who underwent simplified pericardial devascularization (Group A) and 309 patients who underwent traditional pericardial devascularization (Group B) were followed up from 2003' to 2011'. Results were performed with the general condition of the patients and the incidence of complications to assess the value of the two operating methods. RESULTS: The operating time was 1.0-3.83 hours (mean 1.94 +/- 0.32 hours) in Group A versus 1.67-4.50 hours (mean 2.86 +/- 0.40 hours) in Group B. The amount of bleeding, postoperative hospital stay and hospitalization expenses were 110 500 ml (mean 224.81 +/- 78.44 ml), 7-22 days (mean 10.41 +/- 4.01 days) and 15700 27500 yuan with an average of 19300 +/- 1600 yuan in Group A and 200-700 ml (mean 423.50 +/- 85.19 ml), 9-32 days (mean 14.76 +/- 4.52 days) and 18700-44500 yuan with an average of 23400 +/- 2200 yuan in Group B. In September 2012', successful follow-up was completed for 438 patients, of which, 181 underwent the simplified devascularization with 31 patients lost (follow-up rate 85.4%). Meanwhile, 257 patients in Group B were followed up completely and 52 patients were lost (follow up rate 83.2%). The follow-up time ranged from 1 to 9.5 years and the average time was 5.03 +/- 2.13 years. The mortality, rebleeding rate, rate of hepatic encephalopathy, rate of ascites and the incidence of gastric fistula and (or) esophageal fistula were 6.1%, 6.1%, 1.7%, 8.3% and 0 in Group A versus 14.0%, 15.2%, 4.3%, 17.7% and 3.1% in Group B. CONCLUSIONS: The final results suggested that simplified pericardial devascularization performed more effectively and conveniently than the traditional method, depending on the mitigated operative wound and the shortened operation time. We concluded that simplified pericardial devascularization was better in treatment of portal hypertension compared than the traditional method. PMID- 26550365 TI - Assessment of tracheal intubation in adults after induction with sevoflurane and different doses of propofol: a randomly controlled trial. AB - Intubation without prior administration of muscle relaxants is a common practice in children and adults with potential difficult airways. We aimed to investigate the effects of adding different doses of propofol on tracheal intubation and the time to return of spontaneous breathing during inhalation induction of patients. 150 patients undergoing operations were randomly given propofol IV at 1.0, 1.5 and 2.0 mg/kg (namely 1.0-propofol, 1.5-propofol and 2.0-propofol, respectively) after inhalational induction with sevoflurane. Tracheal intubating conditions, time to return of spontaneous breathing, postoperative hoarseness, end-tidal carbon dioxide concentration (PETCO2), and pulse oxygen saturations (SpO2) were assessed. Tracheal intubation was successful in all patients. Intubating conditions were acceptable in 31/50, 42/50 and 47/50 in those subjects given propofol 1.0, 1.5 or 2.0 mg/kg, respectively. Intubation scores were similar in groups 1.5-propofol and 2.0-propofol, and were significantly higher than in group 1.0-propofol (P = 0.013). Time to return of spontaneous breathing in group 2.0 propofol was significantly prolonged compared with groups 1.5-propofol and 1.0 propofol (197.0 +/- 49.4 sec vs. 130.4 +/- 32.7 sec, P < 0.001; 197.0 +/- 49.4 sec vs. 104.8 +/- 22.6 sec, P < 0.001, respectively). SpO2 in group 2.0-propofol was significantly lower than group 1.0-propofol and 1.5-propofol. However, PETCO2 in group 2.0-propofol was significantly higher than in groups 1.0-propofol or 1.5 propofol. Propofol at a dose of 1.5 mg/kg provides intubating conditions similar to propofol at 2.0 mg/kg in patients. Time to return of spontaneous breathing followed by a dose of 1.5 mg/kg propofol was significantly shorter than that followed by a dose of 2.0 mg/kg propofol. PMID- 26550366 TI - Analysis of the serum reproductive system related autoantibodies of infertility patients in Tianjin region of China. AB - OBJECT: Reproductive system related autoantibodies have been proposed to be associated with natural infertility. However, large scale systematic analysis of these of antibodies has not been conducted. The aim of this study is to analyze the positive rate of antisperm antibody (ASAb), anti-endometrium antibody (EMAb), anti-ovary antibody (AOAb), anti-zona pellucida antibody (AZP) and anticardiolipin antibody (ACA) in infertility patients in Tianjin region of China. METHODS: 1305 male and 1711 female primary infertility patients and 1100 female secondary infertility patients were included in this study, as well as 627 healthy female controls. The above autoantibodies were tested and the positive rates in each group were calculated. RESULTS: the positive rate of ASAb were significantly higher in primary infertility female than that in male, further analysis revealed that primary infertility population all exhibit significant higher positive rate of EMAb, AOAb, AZP and ACA compared with control group. Furthermore, the positive rates of all the antibodies in primary infertility female were significantly higher than those in secondary infertility female. CONCLUSIONS: Our study thus indicates that these autoantibodies might be associated with immunological related primary infertility and may have clinical significance in its diagnosis and treatment. PMID- 26550367 TI - The influence of hypoglycemic drugs on exercise-mediated hypoglycemic effects in elderly type 2 diabetic patients. AB - BACKGROUND: To evaluate the impact of different hypoglycemic drugs on exercise mediated blood glucose (BG) reduction. METHODS: One-hundred and five retirees who were diagnosed with type 2 diabetes mellitus (T2DM) within a two-year period were included in this study. The participants were instructed to walk for 20 to 30 minutes at a moderate-speed (4.0 to 4.5 km/h) after breakfast. Blood pressure and fingertip BG were measured before and after walking. RESULTS: The rate of BG reduction was significantly higher in all exercise groups when compared to that of non-exercised patients. Among all groups, BG declined the most in the un medicated group, while the lowest BG reduction was observed in the acarbose group. Surprisingly, the BG reduction in acarbose group was significantly lower when compared with non-acarbose groups (P<0.0001). Interestingly, after further correcting for sex, age, BMI, diabetes history, walking time, walking speed and walking distance, only age was found to be an influencing factor (t=-3.304, P=0.001). Pearson correlation of age and BG reduction showed that correlation coefficient of age was only 0.183 and revealed no statistical significance. CONCLUSIONS: Walking at a moderate speed for 20 to30 minutes after breakfast provided a beneficial BG reduction effect in elderly T2DM patients. Among the medicated groups, the smallest BG reduction rate was observed in patients taking acarbose. We suggest that acarbose might influence hypoglycemic effects of exercise. The results of this study will be helpful for determining the best clinical usage of hypoglycemic medications in elderly T2DM patients. PMID- 26550368 TI - Relationship between chronic tonsillitis and Henoch-Schonlein purpura. AB - The aim of this study was to explore the relationship between children's chronic tonsillitis and Henoch-Schonlein purpura (HSP). We randomly selected 56 cases of HSP children with chronic tonsillitis during December 2009 to December 2012, 26 cases for surgery group and 30 cases for non-surgery. The duration of abdominal pain and rash, 24 hours urine protein quantity, urine red blood cell count, titre of anti streptolysin O (ASO) and complement C3 (C3) were compared and analyzed with statistical method. Compared with the non-surgery group, the duration of abdominal pain and rash, overcast days of urine protein and occult blood in the surgery group were improved significantly (P < 0.05). 24 hours urine protein quantity and urine red blood cell count of the surgery group were improved significantly after surgery (P < 0.01). Chronic tonsillitis was one of the important factors leading to recurrent rash and inducing Henoch-Schonlein purpura nephritis. Tonsillectomy was an alternative mean to treat HSP children with chronic tonsillitis. PMID- 26550369 TI - The association between SDF-1 G801A polymorphism and non-small cell lung cancer risk in a Chinese Han population. AB - BACKGROUND: SDF-1 G801A polymorphism is reported to correlate with cancer susceptibility. However, the association between SDF-1 G801A polymorphism and non small cell lung cancer (NSCLC) risk in Chinese populations remains unknown. MATERIAL AND METHODS: A total of 408 NSCLC patients and 303 health controls included in this study. Restriction length fragment polymorphism (RFLP) analysis was used to assess the frequencies of SDF-1 G801A polymorphic variant. RESULTS: No significant association was found between SDF-1 G801A polymorphism and NSCLC risk (OR=1.268, 95% CI 0.811-2.583, P=0.361). Furthermore, SDF-1 G801A polymorphism was not correlated with histological type (P=0.697) and TNM stage (P=0.276). CONCLUSION: SDF-1 G801A polymorphism was not a risk factor for NSCLC in Chinese Han population. PMID- 26550370 TI - Liver kinase B1 promoter CpG island methylation is related to lung cancer and smoking. AB - The aim of this study was to explore the association of CpG islands methylation of liver kinase B1 (LKB1) with primary lung cancer and smoking, providing a theoretical basis for the demethylating drug to treat lung cancer by detecting the LKB1 promoter CpG methylation. mRNA expression of LKB1 were detected by in situ hybridization and methylation status on Hap II locus of the promoter of LKB1 was analyzed by methylation-specific polymerase chain reaction (PCR). 7 of 80 LKB1 positive cases had methylation on CpG islands while 18 of 44 LKB1 negative cases had methylation on CpG islands. The difference was significant between CpG island methylation and LKB1 expression. 8 of 54 cases of early and middle lung cancer were detected LKB1 promoter CpG island methylation while 30 controls were not detected, the difference was significant. 5 of 64 more-than-5-year cases had methylation on CpG islands while 20 of 60 less-than-5-year cases had methylation. The difference was significant between of 5-year survival and CpG island methylation of LKB1. 22 of 74 smoking cases of lung cancer had methylation on CpG islands of LKB1 while only 3 of 50 non-smoking cases had methylation. The difference of smoking and CpG island methylation of LKB1 was significant. LKB1 promoter CpG islands aberrant methylation is closely associated with the occurrence, development and prognosis of lung cancer, especially with smoking history including clinical early diagnosis and prognosis. CpG islands methylation in the promoter of LKB1 is likely important one of the mechanism of smoking associated lung cancer. PMID- 26550371 TI - Distribution of monocyte chemoattractant protein-1 (MCP-1 A-2518G) and chemokine receptor (CCR2-V64Iota) gene variants in hyperbilirubinemic newborns. AB - Hyperbilirubinemia is one of the most crucial syndromes, which is characterized by high levels of bilirubin, especially when it occurs in newborns. Bilirubin has cytoprotective properties with an antioxidant function and plays several major roles in the inflammation process with its members such as chemokines. The monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family and it has been associated with the inflammatory process. There are no data on the chemokine and its receptor genotypes in hyperbilirubinemic newborns to show their distribution. The aim of this study is to investigate the genotypic relationship of MCP-1 and its receptor CCR2-V64Iota with hyperbilirubinemia in Turkish newborns. A total of 85 newborns were included in the study: 20 infants with hyperbilirubinemia (hyperbilirubinemic group) and 65 infants without hyperbilirubinemia (non-hyperbilirubinemic group). Genotyping of MCP-1 A-2518G and CCR2-V64Iota gene polymorphisms were detected by PCR-RFLP, respectively. MCP 1 GG genotype in patients was higher than the controls and this genotype had 2.69 times higher risk for hyperbilirubinemic neonates (P: 0.20). The frequency of MCP 1 A-2518G G+ genotype in patients was higher than the controls (55.0% and 38.5%, respectively). The results of our preliminary study suggest that MCP-1 G+ genotype has the ability to increase the hyperbilirubinemia risk of newborns. These results should be focused on to research on a larger scale to confirm the findings. PMID- 26550372 TI - Efficiency of treatment with rituximab in platelet transfusion refractoriness: a study of 7 cases. AB - OBJECTIVE: The purpose of our study was to evaluate the efficacy and safety of rituximab in treatment of immune PR. METHODS: We retrospective analysis 7 paitents (5 aplastic anemia, 2 myelodysplastic syndrome) with immune PR who received at least 3 weekly infusions of rituximab (375 mg/m(2)). RESULTS: All enrolled patients acquired improvement of platelets transfusion more than 2 months (CCI >= 4.5 * 10(9)/L). We first found that there were 2 patterns of response to rituximab treatment in patients with immune PR, which the early but transient after the first rituximab administration and the late but continuous beginning to appear at 3 weeks from the start of treatment. CONCLUSION: Rituximab is a promising treatment in patients with immune PR and giving the opportunity and time for cure the disease. PMID- 26550373 TI - Traditional Chinese medical herbs staged therapy in infertile women with endometriosis: a clinical study. AB - BACKGROUND: Endometriosis is a common gynecological disease defined as the presence of endometrioid tissue (glands and stroma) outside the uterus. About 30 to 40% patients with endometriosis are infertile. In traditional Chinese medical system, endometriosis associated infertility is mostly caused by kidney deficiency and blood stasis. The herb of reinforcing kidney and removing blood stasis is designed to treat the disease. MATERIAL AND METHODS: All the 80 up-to standard patients were divided into two different groups exactly according to the random principle. They were treated with hormone and traditional Chinese medical herb separately. After half year's therapy, all the patients received one year's follow-up. Their transvaginal ultrasonographic changes, serum hormone levels and pregnancy rate were recorded to analysis the effect. RESULTS: No significant difference happened in two groups' demographic and clinical characteristics (P > 0.05). After the treatment, the effect on serum hormone levels and specific markers are significant (P < 0.05). The transvaginal ultrasonographic changes were positive, too. The text on hepatic and renal function confirmed to the safety of the herb. Compared to hormone therapy, the traditional Chinese medical herb is safe and effective for endometriosis patients with infertility. CONCLUSION: Compared with hormone therapy, traditional Chinese medical herb's two staged therapy is effective and safe for endometriosis patients with infertility. PMID- 26550374 TI - Tongue acupuncture in treatment of post-stroke dysphagia. AB - Tongue acupuncture is a technique that treats illness through acupuncture applied to the tongue. This study was designed to assess its therapeutic effects in the treatment of post-stroke dysphagia. A clinical control study was conducted with randomly selected 180 patients with post-stroke dysphagia. The patients were assigned into 2 groups: 90 in the Tongue acupuncture group received tongue acupuncture on the basis of conventional medication, 90 in the conventional acupuncture group received acupuncture on the neck and wrist. Acupoints in the tongue are Juanquan (EX-HN10) (at the midpoint of dorsal raphe of the tongue) and Haiquan (EX-HN11) (Sublingual frenulum midpoint). Acupoits on the body are Fengchi (GB20) and Neiguan (PC6). The effective rate, the national institutes of health stroke scale (NIHSS), TV X-ray fluoroscopy swallowing function (VFSS), the incidence rate of pneumonia were used to evaluate the efficacy after 4 weeks treatment. The NIHSS and VFSS of tongue acupuncture group were improved significantly than that of the conventional group (P < 0.01, respectively). The incidence rate of pneumonia decreased (P < 0. 01). The effective rate of the tongue acupuncture group was higher than that of conventional group (96.67% vs. 66.67%, P < 0. 01). On the basis of the conventional medication, tongue acupuncture would effectively improve the swallow functions, decrease the neurological deficit and reduce the incidence of pneumonia in patients with post stroke dysphagia. PMID- 26550375 TI - Glycididazole sodium combined with radioiodine therapy for patients with differentiated thyroid carcinoma (DTC). AB - The aim of the present study was to evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with radioiodine therapy for patients with DTC cervical metastases. 53 patients of DTC cervical lymph node metastasis were randomly divided into 2 groups, where 24 cases were treated with 4.44 GBq of (131)I alone, 29 cases were treated with 800 mg/m(2) of CMNa combined with 4.44 GBq of (131)I. Peripheral blood samples were collected before and after treatment to perform measurements of routine blood test, liver function, renal function, parathyroid hormone (PTH), lymphocyte micronucleus rates and chromosome mutation. The results showed that rates of complete response (CR) in CMNa combined with radioiodine group (65.5%) were significantly higher than that in radioiodine monotherapy group (37.5%). Furthermore, CMNa combined with adioiodine treatment significantly increased the percentage of thyroglobulin (Tg) reduction at 12 weeks after treatment (P<0.05). There is no significant difference in blood routine, liver function, renal function, PTH, lymphocyte micronucleus rates and chromosome mutation rates before and 12 weeks after treatment (P>0.05). These results indicate 4.44 GBq of (131)I treatment combined with 800 mg/m(2) of CMNa could significantly improve clinical efficacy of DTC patients without increasing side effects. PMID- 26550376 TI - Factors associated with pancreatic infection in patients with severe acute pancreatisis. AB - OBJECTIVE: To identify potential risk factors associated with pancreatic infection in severe acute pancreatisis (SAP) patients, thus providing evidence for clinical prediction and treatment. METHODS: A total of 42 patients with SAP collected in our hospital from January 2013 to July 2014 were divided into two groups according to the presence or absence of pancreatic infection and retrospectively analyzed. Clinical characteristics and laboratory examine results of the two groups including age, sex, APACHE II score, serum amylase, serum calcium, blood glucose, ALT, AST, hyoxemia, serum albumin, serum creatinine and blood urea nitrogen were investigated for their relevance to pancreatic infection. RESULTS: The overall occurrence of secondary pancreatic infection of the 42 patients was 52.38%. A significantly positive correlation was revealed between the incidence rate of the secondary pancreatic infection and the factors including hyoxemia, blood creatinine and urea nitrogen in SAP patients (P < 0.05 or P < 0.01). Meanwhile, the level of serum albumin was negatively correlated with the rate of secondary infection in SAP patients (P < 0.01). The rest factors showed no significant correlation (P > 0.05). CONCLUSION: Hyoxemia, blood creatinine and urea nitrogen are potential factors leading to pancreatic infection in SAP patients, while an increase of serum albumin may reduce the incidence of infection. PMID- 26550377 TI - Preoperative risk factors for early postoperative urinary continence recovery after non-nerve-sparing radical prostatectomy in Chinese patients: a single institute retrospective analysis. AB - Urinary incontinence (UI) remained a significant complication after radical prostatectomy and led to impaired quality of life. Early continence is a goal to take into consideration for better patient satisfaction after radical prostatectomy. To identify the independent preoperative risk factors associated with UI after radical prostatectomy (RP), we evaluated 446 patients treated with non-nerve-sparing RP between 2010 and 2013 at our institution. The incontinence rate was 98.7% and 46.6% after catheter removal and 3 months after surgery, respectively. We examined several preoperative factors including age, smoking, body mass index (BMI), comorbidities such as hypertension and diabetes, preoperative prostate-specific antigen (PSA) level, Gleason score, and preoperative pelvic floor muscle exercise (PFME). The results suggested preoperative PFME was the only independent protective risk factor for immediate continence after catheter removal. At 3 month following surgery, age at surgery represented a risk factor for delayed continence, while BMI and preoperative PFME were the protective risk factors for postoperative UI. Our results supported that age and preoperative PFME were predictive factors for early continence after RP. These findings could help clinicians to counsel men and their partners about postoperative incontinence. PMID- 26550378 TI - Efficacy of methylprednisolone sodium succinate for injection (postotic injection) on the auditory threshold and speech recognition rate of sudden deafness patients. AB - OBJECTIVE: To investigate the effect of injecting the methylprednisolone in the ear for the sudden deafness and the improvement of speech discrimination test. METHODS: 50 inpatients with a sudden hearing loss were recruited. Inject the methylprednisolone in the subperiosteal of the ear which is 0.5 cm distance to the ear ditch every three days. Methylprednisolone was placed for fifteen days. Simultaneously vasodilation, neurotrophic, thrombolysis and insulin hypoglycemia were administered in all patients. Pure tone test and speech discrimination test were conducted at Days 7 & 14 after intervention. RESULTS: The outcome was as follows: cure (n = 8), efficacy (n = 9), effect (n = 18) and no effect (n = 15) respectively. The overall effective rate of 70%. The improvement of pure tone threshold and speech discrimination had significant statistical difference (P < 0.05). CONCLUSION: The therapy of postaural methylprednisolone injection can decrease pure tone threshold effectively and increased speech discrimination with a sudden hearing loss. PMID- 26550379 TI - Effect of preemptive analgesia with parecoxib sodium in patients undergoing radical resection of lung cancer. AB - OBJECTIVE: To discuss the effect of preemptive analgesia with parecoxib sodium in patients undergoing radical resection of lung cancer. METHODS: 115 cases of lung cancer patients with American society of anesthesiologists class (ASA) grade I~II who received selective operation were randomly divided into the research group and the control group. The research group patients were given preoperative parecoxib sodium 40 mg plus postoperative normal saline 2 ml, while the control group patients were treated with preoperative normal saline 2 ml plus postoperative parecoxib sodium 40 mg. The pain condition at postoperative 1, 2, 4, 8, 12, 24 and 48 h were evaluated by visual analogue scale (VAS), and emergence agitation was tested by agitation score. RESULTS: Finally there were 56 cases and 57 cases can be used for evaluation in the research group and control group. The VAS scores after 1, 2, 4, 8, 12, 24 and 48 h in the research group and control group were [2.23+/-0.45, 2.35+/-0.48, 2.51+/-0.51, 2.41+/-0.45, 2.28+/ 0.42, 2.16+/-0.39, 2.11+/-0.40] and [3.80+/-0.62, 4.01+/-0.64, 4.31+/-0.67, 4.10+/-0.64, 3.65+/-0.70, 3.12+/-0.66, 2.46+/-0.53], respectively. The research group were obviously lower than the control group, the difference were statistically significant (P<0.05). The rate of agitation was 24.44% (11/56) in the research group, significantly lower than the control group of 59.65% (34/57) (P<0.05). CONCLUSION: Preemptive analgesia with parecoxib sodium can obviously relieve acute pain using in patients undergoing radical resection of lung cancer, and is helpful to reduce the incidence of emergence agitation. PMID- 26550380 TI - Analysis on correlation of white matter lesion and lacunar infarction with vascular cognitive impairment. AB - OBJECTIVE: To investigate the correlation of white matter lesion (WML) and lacunar infarction (LI) with vascular cognitive impairment. To investigate the correlation of cognitive changes of vascular dementia (VD) patients with lacunar infarction (LI) and white matter lesion (WML). METHODS: The clinical data of 60 cases of VD patients were evaluated and analyzed by combining with imageological findings and cognitive function assessment. RESULTS: Multiple LI and WML were negatively correlated with both mini-mental state examination (MMSE) scale scores (r = -0.401, P = 0.036) and clock drawing test (CDT) scale scores (r = -0.482, P = 0.028); the LI number in occipital lobe was negatively correlated with MMSE scores (r = 0.338, P = 0.048), the LI number in temporal lobe was negatively correlated with CDT scores (r = -0.235, P = 0.047), and the LI number in frontal lobe was negatively correlated with MoCA scores (r = -0.450, P = 0.039). CONCLUSION: All of LI location and number as well as WML are independent influencing factors of cognitive impairment of VD patients. PMID- 26550381 TI - Effects of epidural analgesia with different concentrations of bupivacaine plus fentanyl on pain in patients undergoing thoracic surgery. AB - OBJECTIVE: To investigate and compared the efficacy and safety of epidural analgesia with different concentrations of bupivacaine plus fentanyl on pain in patients undergoing thoracic surgery. METHODS: 120 cases undergoing elective thoracic surgery were randomly divided into A, B, C and D four groups each with 30 cases, and they were treated with 0.25% (A group), 0.375% (B group), 0.50% (C group) and 0.75% (D group) bupivacaine plus fentanyl 0.4 mg. The pain conditions postoperative 4 h, 8 h, 12 h, 24 h and 48 h were evaluated by visual analogue scale (VAS). The PCA pressing numbers and incidence of adverse reactions were compared between the four groups. RESULTS: By postoperative 4 h, the VAS in D group were obviously lower than those in the other three groups (P all <0.05), and the other three groups showed no significances (P>0.05). However, the four groups showed no significant differences in VAS by postoperative 8 h, 12 h, 24 h and 48 h (P all >0.05). The incidences of respiratory depression in C and D groups were markedly higher than those in A and B groups (P all <0.05). CONCLUSIONS: 0.25%~0.375% bupivacaine plus fentanyl 0.4 mg using in epidural analgesia in patients undergoing thoracic surgery can lead to safe and effective analgesic effect. PMID- 26550382 TI - Evaluating ECG-aided tip localization of peripherally inserted central catheter in patients with cancer. AB - OBJECTIVE: To evaluate ECG-aided tip localization of peripherally inserted central catheter (PICC) in the patients with cancer. METHODS: Between September and December 2014, 170 patients undergoing PICC were divided into observation group and control group (each group with 85 patients). In observation group, patients received ECG-aided tip localization of PICC. In control group, PICC was performed with conventional method. After PICC was performed, all patients took orthophoria chest radiograph (OCR) to check whether the tip position of PICC was appropriate. Finally, successful rate of the first PICC was compared between the two groups. RESULTS: In observation group, OCR showed that the tip of PICC was located in middle and low one-third of superior vena cava in 85 patients. In control group, OCR showed that the tip of PICC was located between superior vena cava and right atrium in 75 patients. The successful rate of the first PICC was significantly higher in observation group than in control group (P < 0.05). CONCLUSION: ECG-aided tip localization of PICC is accurate and safe, and is worth clinically recommending. PMID- 26550383 TI - Treatment of renal uric acid stone by extracorporeal shock wave lithotripsy combined with sodium bicarbonate: 2 case reports. AB - Uric acid stone is the most comment radiolucent renal stone with high recurrence rate, which would further cause acute upper urinary tract obstruction and kidney failure. Here we report two cases of renal uric acid stone from December 2012 to April 2013. One 43-year-old male patient suffered from chronic uric acid nephrolithiasis caused by the long-term indwelling of bilateral double-J stent. Another 69-year-old patient was also diagnosed with uric acid nephrolithiasis at the right kidney. Both patients were first treated with extracorporeal shock wave lithotripsy (ESWL), followed by 1.5% sodium bicarbonate dissolution therapy. After a week of the treatment, the uric acid stones in both patients were completely dissolved without retrograde infection. In summary, the use of ESWL and sodium bicarbonate dissolution therapy as a combined modality is a safe, effective, inexpensive treatment for uric acid nephrolithiasis. PMID- 26550384 TI - The application of temporo-occipital fascial flap in the wound of medium scalp defect with bone exposure. AB - We are aimed to observe the effect of applying the combined temporo-occipital fascial flap in the medium scalp defect with bone exposure. Three cases of moderate scalp defect with bone exposure were admitted by The 89th Hospital of PLA and China-Japan Friendship Hospital from October 2009 to March 2014, and the wounds were repaired by application of the temporo-occipital fascial flap with medium-thickness skin grafting. And then these 3 patients were followed up after the operation, and the wound repair was observed. These 3 cases of fascial flaps all survived well with good appearance and covered the wound completely. Fibrosarcoma of one case had a relapse 3 months after operation, and the other two cases were followed up from 6 months to 3 years. Meanwhile, the appearance and function were satisfactory. The communicating branches between superficial temporal artery and occipital artery are rich. Therefore we designed and utilized the long temporo-occipital fascial flap containing the ipsilateral occipital superficial fascia to repair the scalp defect with bone exposure, and the curative effect is satisfactory. PMID- 26550385 TI - Application of MSCTA combined with VRT in the operation of cervical dumbbell tumors. AB - Cervical dumbbell tumor poses great difficulties for neurosurgical treatment and incurs remarkable local recurrence rate as the formidable problem for neurosurgery. However, as the routine preoperative evaluation scheme, MRI and CT failed to reveal the mutual three-dimensional relationships between tumor and adjacent structures. Here, we report the clinical application of MSCTA and VRT in three-dimensional reconstruction of cervical dumbbell tumors. From January 2012 to July 2014, 24 patients diagnosed with cervical dumbbell tumor were retrospectively analyzed. All patients enrolled were indicated for preoperative MSCTA/VRT image reconstruction to explore the three-dimensional stereoscopic anatomical relationships among neuroma, spinal cord and vertebral artery to achieve optimal surgical approach from multiple configurations and surgical practice. Three-dimensional mutual anatomical relationships among tumor, adjacent vessels and vertebrae were vividly reconstructed by MSCTA/VRT in all patients in accordance with intraoperative findings. Multiple configurations for optimal surgical approach contribute to total resection of tumor, minimal damage to vessels and nerves, and maximal maintenance of cervical spine stability. Preoperative MSCTA/VRT contributes to reconstruction of three-dimensional stereoscopic anatomical relationships between cervical dumbbell tumor and adjacent structures for optimal surgical approach by multiple configurations and reduction of intraoperative damages and postoperative complications. PMID- 26550386 TI - A case of methylprednisolone treatment for interstitial pneumonia induced by gefitinibin. AB - In this case, an old man was diagnosed as lung cancer, clinical stage IV. In order to alleviate cancer, this patient was treated with gefitinib. Three months later, symptoms such as a significant weakness, chest tightness and shortness of breath after sports arised and intensifying. Implosive therapy with high dose methylprednisolone is used to control the weakness caused by gefitinib. Eight days after treatment, patient's condition significantly improved. The use of methylprednisolone can effectively treat interstitial pneumonia induced by gefitinibin, help patients get better from critical condition such as type I respiratory failure. This new discovery is a good guidance for clinical treatment of gefitinibin caused interstitial pneumonia. PMID- 26550387 TI - Single transverse-orientation cage via MIS-TLIF approach for the treatment of degenerative lumbar disease: a technical note. AB - BACKGROUND: Single transverse cage placed in the anterior vertebral column can better maintain lumbar lordosis and sagittal alignment and is frequently used via the lateral transpsoas approach. However, there is no clear description in the literature of the steps required to place the single transverse cage during the instrumented transforaminal lumbar interbody fusion (TLIF) procedure for the treatment of degenerative lumbar disease. The objective of this study is to describe the technique using single transverse-orientation cage when performing TLIF procedures. MATERIALS AND METHODS: We present 18 illustrative cases in which single transverse-orientation cage was placed according to a step-by-step technique that can be used during the TLIF procedure. Information acquired included procedure time, intraoperative blood loss and postoperative complications. The preoperative and postoperative Oswestry Disability Index (ODI) and the visual analogue scale (VAS) scores were recorded. Changes in disc height and segmental lordosis were measured at radiographs. RESULTS: The single transverse-orientation cage was successfully placed in 18 patients in a stepwise technique to achieve lumbar fusion. Using this technique, the patients significantly improved clinically and radiographically at postoperative visits. CONCLUSIONS: This is the first report demonstrating the safety and efficacy of instrumented TLIF with single transverse-orientation cage for the treatment of degenerative lumbar disease. Single transverse-orientation cage via MIS-TLIF approach can maintain greater lumbar lordosis and avoid the unique complications of lateral transpsoas approach. Understanding the options for cage placement is important for surgeons considering the use of this technique. PMID- 26550388 TI - Anesthetic management of a parturient with mirror syndrome: a case report. AB - Mirror syndrome is a rare clinical entity consisting of fetal and placental hydrops with maternal edema. It is associated with an increase in fetal mortality and maternal morbility. We describe the anesthetic management of a parturient with Mirror syndrome complicated by HELLP syndrome and massive postpartum hemorrhage, who required general anesthesia for cesarean delivery. PMID- 26550389 TI - Comparison of the efficacy of recombinant human brain natriuretic peptide with saline hydration in preventing contrast-induced nephropathy in patients undergoing coronary angiography with or without concomitant percutaneous coronary intervention. AB - The incidence of contrast-induced nephropathy has an increasing trend as a result of increased use of contrast media during coronary interventional procedures. Contrast-induced nephropathy is one of the major causes for hospital acquired renal failure after coronary interventional procedures. In this study, a total of 126 enrolled patients undergoing elective coronary angiography and/or percutaneous coronary intervention were randomly divided into two groups to investigate the efficacy of recombinant human brain natriuretic peptide in preventing contrast-induced nephropathy in patients undergoing elective coronary angiography and/or percutaneous coronary intervention. Our results showed that there was no statistically significant difference in the primary end points, with similar incidence of contrast-induced nephropathy in the two groups (P=0.770). In compared with the hydration group, the elevation of serum creatinine in the recombinant human brain natriuretic peptide group was less, especially at 48 hours (P=0.047) and at 72 hours (P=0.048) after the procedure. The creatinine clearance from baseline to 72 hours after the procedure was higher in the BNP group than in the hydration group. There were significant differences in creatinine clearance at 48 hours (P=0.016) and at 72 hours (P=0.019) between the two groups. In spite of similar incidence of contrast-induced nephropathy, recombinant human brain natriuretic peptide has its advantages for the protection of the renal function associated with better protection of renal function in patients undergoing elective coronary angiography and/or percutaneous coronary intervention, compared with saline hydration. PMID- 26550390 TI - A giant symptomatic cardiac lipoma recurring at the fifth year. AB - Cardiac lipomas are extremely rare in the heart diseases and only few present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 48-year-old woman who with a 2-year history of recurrent dyspnea with mild anemia was admitted to our hospital as a huge mass was found in her mediastinum. After complete surgical tumor resection, she was recurred at the fifth year. This case underlines the giant cardiac lipomas had a slightly higher risk of recurrence over the next five years. PMID- 26550391 TI - Dangerous blind tracheal intubation attempt due to fiberscope non-availability in a pediatric patient with retropharyngeal abscess caused by a large fish bone. AB - In China, foods containing bones are sometimes fed to young infants. Occasionally, this practice results in bone aspiration and retropharyngeal abscess, a potentially life-threatening infection in the deep space of the neck that can compromise the airway. The main concern in managing patients with retropharyngeal abscess is airway management. In China, not all hospitals and operating rooms are equipped with fiberscopes, particularly pediatric-size fiberscopes. Emergency airway management can be dangerous when a fiberscope is unavailable. We present the case of a 21-month-old baby girl with a retropharyngeal abscess secondary to fish bone ingestion. During an attempted blind tracheal intubation due to fiberscope non-availability, the abscess ruptured, and the pus released from it obstructed the airway. The patient was successfully treated despite the inadequate resources and dangerous complication. We recommend a detailed preoperative airway assessment and preparation for fiberscopic tracheal intubation in such patients to prevent this dangerous complication. PMID- 26550392 TI - Mixed epithelial and stromal tumor of the kidney: a rare case report and review of the literatures. AB - Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare complex renal neoplasm composed of a mixture of cystic and solid components. Until date only few cases of MESTK have been reported. We present here a rare case of MESTK that was diagnosed in a 56-year-old female. The patients were referred to our hospital due to a mass on the right kidney identified incidentally in a routine physical examination. A pre-operative diagnosis of cystic renal cell carcinoma was made and a right radical nephrectomy was carried out. Macroscopically, a cystic tumor was noticed in the upper portion of the right kidney. Various-sized cysts accompanied by multiple cysts and few solid areas were observed. Immunohistochemically, various epithelial markers as well as stromal markers were identified. Taken together with all the immunohistochemical results and morphological pattern of the tumor, a diagnosis of MESTK was made. MESTK is relatively rare and generally benign. However, it is difficult to distinguish between benign or malignant tumors according to the current radiological method. Therefore a complete resection of the tumor by partial or radical nephrectomy is suggested. PMID- 26550393 TI - Adding dexmedetomidine to ropivacaine for lumbar plexus and sciatic nerve block for amputation of lower limb in high-risk patient-a case report. AB - The ischemia necrosis of limb frequently requires surgery of amputation. Lumbar plexus and sciatic nerve block is an ideal intra-operative anesthetic and post operative antalgic technique for patients of amputation, especially for high-risk patients who have severe cardio-cerebrovascular diseases. However, the duration of analgesia of peripheral nerve block is hardly sufficient to avoid the postoperative pain and the usage of opioids. In this case, a 79-year-old man, with multiple cerebral infarcts, congestive heart failure, atrial flutter and syncope, was treated with an above knee amputation because of ischemia necrosis of his left lower limb. Dexmedetomidine 1 MUg/kg was added to 0.33% ropivacaine for lumbar plexus and sciatic nerve block in this case for intra-operative anesthesia and post-operative analgesia. The sensory function was blocked fully for surgery and the duration of analgesia maintained 26 hours with haemodynamic stability and moderate sedation. The patient did not complain pain and require any supplementary analgesics after surgery. This case showed that adding 1 MUg/kg dexmedetomidine to ropivacaine for lumbar plexus and sciatic nerve block may be a feasible and safe technique for high-risk patients for lower limb surgery of amputation. PMID- 26550394 TI - Double-level osteotomy and one-stage reconstruction with long intramedullary femoral nail to correct a severe proximal and diaphyseal femur deformity in a patient with polyostotic fibrous dysplasia: case report and literatures review. AB - Proximal femur is often involved with varus and retroversion deformity in polyostotic fibrous dysplasia (PFD). Multiple corrective osteotomies with intramedullary nails in two stages is recommended procedure as some authors described. We report a case using double-level osteotomy and one-stage reconstruction with intramedullary nail in a patient with painful proximal femur and diaphysis varus deformity, the neck-shaft angle was corrected from 95 degrees pre-operatively to 125 degrees post-operatively, the patient was free of pain and no evidence of recurrence at the 24-month follow up. The operative design and method were described, and a review of related literatures about the treatment alteration for PFD and relevant operative selection were also performed. PMID- 26550395 TI - Uterine artery embolization for hemorrhage resulting from second-trimester abortion in women with scarred uterus: report of two cases. AB - This study was conducted to investigate the effect of uterine artery embolization for the treatment of hemorrhage following second-trimester labor induction for women with scarred uterus. Two cases of second-trimester abortion were retrospectively reviewed, both of which had a history of caesarean delivery and were complicated by gestational anemia. One was at 18 weeks' gestation and presented with persistent vaginal bleeding for two months resulting in relatively large area of blood clot in uterine cavity. The other was at 25 weeks' gestation with partial hydatidiform mole and presented with intermittent vaginal bleeding. Both patients presented with continuous and heavy vaginal bleeding after oral administration of mifepristone for labor induction, with one cervix left unopened, while the other cervix 3 cm left dilatation, yet felt obstructed by pregnant tissue. Both patients were immediately treated with uterine artery embolization (UAE). Both patients presented with alleviated hemorrhage and regular uterine contraction after UAE, followed by smooth induction of labor. No hemorrhage occurred since then during the follow-up. The results suggest that UAE is safe and effective for the treatment of massive hemorrhage of second-trimester abortion in women with scarred uterus. It can reduce time period of labor induction and alleviate hemorrhage, which not only rescues patients but also avoids cesarean sections and retains fertility for the pregnant. PMID- 26550396 TI - Common variable immune deficiency associated Hodgkin's lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report. AB - Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin's lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26*17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 MUg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes for our patient inability to control his EBV infection which eventually lead to hemophagocytic lymphohistiocytosis. To conclude, rare simultaneous manifestation of primary immune deficiencies (PID), Hodgkin's lymphoma and EBV-HLH occurred in our patient which have concordant immunological mechanism that eventually lead poor prognosis in our patient. PMID- 26550397 TI - A T-cell prolymphocytic leukemia case with central nervous system involvement. AB - T-cell prolymphocytic leukemia (T-PLL) is an aggressive mature T cell neoplasm that typically involves peripheral blood, bone marrow, lymph nodes and spleen. It is a rare disease that comprises 2-5% of mature lymphocytic leukemia in adults. Here we present a T-PLL patient with CNS involvement. A 74-year-old man admitted to a hospital in April 2014 with vomiting. He was diagnosed as chronic lymphocytic leukemia (CLL) and R-CVP (Rituximab, cyclophosphamide, vincristine and prednisolone) chemotherapy protocol was started. After the first two cycles of chemotherapy, the patient's mental functions improved. However after the 3(rd) cycle of chemotherapy was given in July 2014 the general situation of the patient deteriorated and ptosis of the left eye and facial paralysis developed. Then the patient was referred to our medical center. An MR of the brain revealed linear contrast enhancement around the bilateral 3(rd), 7(th) and 8(th) cranial nerves which indicated cranial involvement by the lymphoproliferative process (Figure 1). Cerebrospinal fluid cytological examination confirmed the diagnosis. Based on these and bone marrow aspiration and biopsy findings a diagnosis of T-PLL was rendered (Figure 3). In September 2014 the patient died suddenly due to a cardiac arrest. Differential diagnosis is very important in T-PLL. Both T-PLL and chronic lymphocytic leukemia (CLL) may present with splenomegaly and lymphocytosis as well as circulating prolymphocytes in blood. Typical CLL cells are like mature lymphocytes with dense nucleus and aggregated chromatin. To conclude, CNS involvement in T-PLL is a rare finding and differential diagnosis of T-PLL is very important. PMID- 26550398 TI - Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient. AB - In the clinical setting, bleeding is a common manifestation of acute promyelocytic leukemia (APL), whereas thrombosis is relatively rare, especially as an initial symptom. Here, we report an unusual case of APL with acute myocardial infarction as the first manifestation and cerebral infarction as the relapse manifestation in a healthy young woman. This unique case emphasizes that a thrombotic event could be the first manifestation of an underlying hematological disorder such as APL and could also be a sign of relapse. Rapid detection of the underlying disorder and the timely use of anticoagulation therapy and ATRA are crucial for preventing further deterioration of the disease and saving the patient's life. PMID- 26550399 TI - Severe injury of bilateral elbow joints with unilateral terrible triad of the elbow and unilateral suspected terrible triad of the elbow complicated with olecranon fracture: one case report. AB - Terrible triad of the elbow is characterized as posterior dislocation of the elbow joint accompanied by the fractures of the radial head and coronoid process of the ulna, which is rarely seen in clinical practice, especially because the mild fracture is barely detected by imaging method In this study, we reported one case of serious complex bilateral elbow injury, presenting with unilateral typical terrible triad of the elbow and suspected terrible triad of the elbow complicated with olecranon fracture on the other side. Clinical experience was obtained during the diagnosis and treatment procedures. PMID- 26550400 TI - The first calcified acoustic neurinoma identified in China: a case report and literature review. AB - Here we reported the first case of left cerebellopontine angle acoustic neurinoma with calcification in our department. The patient was 65 year-old, suffering from progressive loss of hearing in the left ear for about 30 years and headache with unsteady gait for approximately 6 months. Head CT & MRI scan identified an intracranial lesion located on left cerebellopontine angle. Left suboccipital retrosigmoid approach was applied to perform the operation after patient consent. The tumor was completely resected without complication and the patient recovered well. Histological findings revealed Spindle-shaped tumor cells tightly compacted to form the Antoni A region, while loosely arranged to form the Antoni B region. Hyaline degeneration and calcification formation were observed across the majority of the tumor. PMID- 26550401 TI - Invasive fungal infection caused by geotrichum capitatum in patients with acute lymphoblastic leukemia: a case study and literature review. AB - Geotrichum capitatum infection has a very low incidence rate with atypical clinical symptoms, making diagnosis difficult, and it has a poor prognosis. The incidence is even more rare in China. This paper reports the first case of infection caused by G. capitatum during bone marrow suppression after chemotherapy in a Chinese patient with acute lymphoblastic leukemia. In addition, it reports a systematic literature review of diagnosis and treatment. The patient with acute lymphoblastic leukemia was confirmed to be infected with G. capitatum, involving lung, liver and skin, through a blood culture test. Caspofungin, amphotericin B loposome, and a combination therapy of amphotericin B liposome and voriconazole were used in succession for treatment. Despite normal body temperature and a slight improvement of clinical symptoms with the combination therapy treatment, the patient died 40 days after chemotherapy due to heart and lung failure. PMID- 26550402 TI - Stent implantation technique through PEG-like pathway for treatment of malignant gastroduodenal obstruction. AB - OBJECTIVE: To investigate feasibility and safety of stent implantation technique through percutaneous endoscopic gastrostomy (PEG)-like pathway for treatment of malignant gastroduodenal obstructions. METHODS: Twelve patients with malignant gastroduodenal obstructions accepted PEG-like operations. A stent implantation pathway was established in abdominal wall under endoscopic guide. A guide wire and a stent release device were introduced through this pathway followed by an intestinal stent implantation. After operation, efficacy and safety of this technique were assessed by collecting data such as operation time, complications, postoperative medication, and hospitalization time during postoperative 2-12 months of follow-up. RESULTS: Twelve patients were successfully treated with stent implantation technique through PEG-like pathway for the first time. The average operation time was 31 minutes. No severe complications occurred during treatment. On the fourth days after operation, patents were give liquid diet and treatment of rehydration, acid suppression, hemostasis and anti-inflammation. The average hospitalization time was 5 days. The follow-up time was 2-12 months. Twelve (100%) patients achieved complete remissions. The stent related complications and obstruction did not appear within 2 months after operations. The quality of life improved significantly. CONCLUSION: The stent implantation technique through PEG-like pathway for treatment of malignant gastroduodenal obstruction is a feasible, effective, and safe choice. PMID- 26550403 TI - A hepatic cancer patient with Guillain-Barre syndrome during the perioperative period of partial hepatectomy: a case report. AB - We reported a case of hepatic cancer patient with Guillain-Barre syndrome during the perioperative period of partial hepatectomy in the present study. We analyzed the clinical data and described the characteristics of this patient. PMID- 26550404 TI - Restricted diffusion in the splenium of the corpus callosum in organophosphate induced delayed neuropathy: case report and review of literatures. AB - We described a 35 year-old female who developed organophosphate induced delayed neuropathy (OPIDN) with an unusal clinical manifestation and neuroradiological presentation. CASE REPORT: A 35-year-old woman came into contact with organophosphate pesticide by remissly inhalation. She got transient unconsciousness lasting for nearly 2 hours and developed transient hematuria and hyperhidrotic subsequently. She received atropine as treatment and got a satisfying recovery and was hospital discharged without any symptoms. But 20 days later the patient displayed symptoms including headache, vertigo, mental and memory decline, and was hospitalized again. Clinical manifestations, laboratorial findings, images data will be presented. The brain magnetic resonance imaging (MRI) showed an unusal neuroradiological presentation characterized by restricted diffusion in the splenium of the corpus callosum. The patient recovered satisfactorily after administration of corticosteroids and immunogloblin. CONCLUSION: OPIDN may develop in some susceptible individuals even by inhalation and sometimes with central nervous system involvement. Treatment with corticosteroids and intravenous immunogloblins was found to achieve good results. PMID- 26550405 TI - Zebra guidewire damage by Holmium: YAG laser and management of removal. AB - The zebra guidewire is widely used in endoscopic surgery. Because of its central mental core, it is not easy to break or shear off within the urinary tract. We report a case about the breakage of zebra guidewire in ureteroscopy (URS) with Holmium: YAG laser lithotripsy. It is easily to be managed by percutaneous access or open surgery. For the purpose of minimal invasiveness and risk, we performed a retrograde flexible ureteroscopy and extracted it successfully without any complication. To our knowledge, this is the first case report on flexible ureteroscopy to remove the residual tip of damaged guidewire in renal. PMID- 26550406 TI - Successful laparoscopic common bile duct exploration in a patient with factor V deficiency, a case report and review of literature. AB - Factor V deficiency is a rare bleeding disorder. Fresh frozen plasma (FFP) is the only source of factor V because factor V concentrates is not available now. We present here a patient had concomitant gallbladder and common bile (CBD) stones with factor V deficiency. The patient is successfully treated by laparoscopic CBD exploration and cholecystectomy with perioperative fresh frozen plasma transfusion. To best of our knowledge, this is the first report of laparoscopic surgery successfully performed in a factor V deficiency patient. Our result suggest that laparoscopic surgery in a factor V deficient patient can be performed safely if normal coagulation profile is achieved after injection of FFP. Our experience in this case also indicate that the incidence of delayed bleeding after surgery is low once hemostasis is successfully obtained during operation and there is no need to continue FFP infusion beyond day 2 postoperative. PMID- 26550407 TI - Unilateral internuclear ophthalmoplegia with upbeat nystagmus from ischemic origin: evidence for the paramedian tract neurons as a vertical neural integrator? AB - Only a few cases with unilateral internuclear ophthalmoplegia have been reported presenting vertical nystagmus, and few of them provides convincing evidence for the paramedian tract neuron to be a vertical neural integrator. We report a patient who suffered from confined dorsal mid-upper pontine infarction showing unilateral internuclear ophthalmoplegia with upbeat nystagmus in primary position. This case possibly provide evidence that paramedian tract neurons may act as a vertical neural integrator in human. PMID- 26550408 TI - Orbital apex syndrome and meningoencephalitis: a rare complication of herpes zoster. AB - Orbital apex syndrome is a rare manifestation of Herpes Zoster (HZ). HZ Mmeningoencephalitis are also rare in immunocompetent persons. We report a rare case that was considered to be HZ meningoencephalitis with orbital apex syndrome in an immunocompetent female. The patient initially manifested with HZ skin lesions and lose of her left sight, diplopia, ptosis, followed by headache, neck pain, and fever, dizziness. Cerebrospinal fluid analysis showed elevation of lymphocytes and protein. A MRI abnormality was remarkable for the presence of a left cerebellum, occipital lobe as well as dura lesion. Head computed tomography and Magnetic resonance venography was normal. Corticosteroid therapy and antiviral therapy was effective to decrease the headache and skin pain. Symptoms were markedly improved after corticosteroid therapy. Three months later, we called the patient to follow up. Her meningoencephalitis symptom recovered. Her follow up brain MRI was normal. But left blindness and external ophthalmoplegia was persistent. This case suggested HZ could affect central nervous system and peripheral nervous system at the same time. PMID- 26550409 TI - Abdominal pain and diarrhea caused by splenic arteriovenous fistula: a case report. AB - Abdominal pain and diarrhea were the most common symptoms in clinics, which could be caused by various diseases such as acute gastroenteritis, intestinal cancer and so on. Here, we report an unusual case of splenic arteriovenous fistula (SAVF) with splenectomy history. Our patient was initially presented with the symptoms of abdominal pain and diarrhea. The diagnosis of SAVF was identified by computed tomography angiography and Doppler's ultrasonic examination. The patient with SAVF was successfully cured by surgical ligation and recovered uneventfully postoperatively. PMID- 26550410 TI - Gene expression profile of human esophageal squamous carcinoma cell line TE-1. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly causes of cancer worldwide. However, to date, the mechanisms underlying its pathogenesis remain unclear. The present study investigated the gene expression profile of human esophageal cancer cell line TE-1, a cell model for ESCC, to gain insight to the genetic regulation of this disease. Human esophageal cancer TE-1 cells and normal esophageal HET-1A cells were cultured for isolation of total RNA. Differential expression of RNA transcripts was assessed using the Agilent 4*44 K microarray, combined with real-time PCR (qRT-PCR) for validation. Classification and function of the differential genes were illustrated by bioinformatics processing including hierarchical clustering and gene ontology (GO) analysis. We identified 4,986 transcripts with differential expression (fold change >=1.5, P<0.05), including 2,368 up-regulated and 2,618 down-regulated transcripts. GO analysis showed that the dysregulated transcripts were associated with biological process, cellular component, and molecular function. After bioinformatic analysis of significantly regulated signaling pathways, we found these transcripts may target 35 gene pathways, including p53 signaling, glioma, ubiquitin-mediated proteolysis, insulin signaling, cell cycle, inositol phosphate metabolism, mTOR signaling, and MAPK signaling. The differentially expressed transcripts were screened between the esophageal cancer cell line TE-1 and normal esophageal cell line HET-1A, as well as their target gene pathways. Further data mining is related to prevention and treatment of esophageal cancer. PMID- 26550411 TI - Leptin receptor gene polymorphisms and risk of hypertension: a meta-analysis. AB - OBJECTIVE: To assess the relationship between the polymorphisms of leptin receptor gene and hypertension. METHODS: Meta analysis was conducted by using RevMan 5.3. Relevant literatures were retrieved by searching PubMed using the keywords "Hypertension", "Leptin Receptor", "OB Receptor", "LEPR Protein". RESULTS: Fifteen studies with a total of 5955 patients with hypertension and 3830 healthy controls were included in this meta-analysis. The results showed that Gln223Arg gene polymorphism was significantly higher in hypertension patients than in control (OR=1.36, 95% CI=1.23-1.51, P<0.00001). However, no statistically significant difference was found in Lys109Arg polymorphism between hypertension patients and control (OR=0.99, 95% CI=0.85-1.16, P=0.91). CONCLUSION: Gln223Arg, but not Lys109Arg gene polymorphism, is higher in hypertension patients, suggesting that patients with Gln223Arg allele carry a higher risk to develop hypertension. PMID- 26550412 TI - Optic radiation mapping reduces the risk of visual field deficits in anterior temporal lobe resection. AB - Anterior temporal lobe resection (ATLR) is often complicated by superior quadrant visual field deficits (VFDs) because of damage to the anterior portion of the optic radiation (Meyer's loop). This study reports the evaluation of optic radiation mapping in protecting against VFDs in the ATLR. We retrospectively analyzed 52 patients with medically refractory temporal lobe epilepsy undergoing ATLR between January 2012 and December 2013. The surgical operations in Group I (n=32) were performed with the modified ATLR, and the operations in Group II (n=20) were aided by combining optic radiation mapping by diffusion tensor imaging, microscopic-based neuronavigation and the intraoperative magnetic resonance imaging (iMRI) technique. A t-test was used to compare the size of ATLR, and a chi square test was applied for the postoperative VFD and seizure outcomes. The optic radiation was reconstructed in all patients in Group II. The size of ATLR was 5.11+/-1.34 cm (3.3-8 cm), and 3.24+/-0.75 cm (2.2-4.8 cm) in Groups I and II, respectively; the size of ATLR was significantly smaller in Group II (F=9.803; P=0.00). The visual fields assessment by the Humphrey Field Analyser 30-2 test showed 27 patients (84.4%) in Group I suffered VFDs at 3 months post-operation, whereas only eight patients (40.0%) in Group II showed VFDs (Pearson chi square =11.01; P=0.001). The 6-month follow-up survey showed that 90.6% of patients in Group I achieved a good outcome (Engel class I-II), outperforming 85.0% in Group II, however, there was no statistically significant difference (chi square =0.382, P=0.581). This techniques of combining optic radiation mapping, microscopic-based neuronavigation and iMRI aided in precise mapping and hence reduction of the risk of visual field deficits in ATLR. The size of ATLR guided by optic radiation mapping was significantly smaller but the seizure outcome was not significantly affected. PMID- 26550413 TI - Effect of GABA on blood pressure and blood dynamics of anesthetic rats. AB - BACKGROUND: This study aimed to investigate GABA effects on blood pressure and blood dynamics of anesthetic rats by observing spontaneously hypertensive rats under both anesthesia and waking state. MATERIALS AND METHODS: 72 male waking Wistar-Kyokos (WKY) rats and 72 male anesthetized spontaneously hypertensive (SHR) rats were randomly divided into control group and experimental group (N = 36 each). Rats were further divided into three subgroups (N = 12 each), which received 15 MUmol GABA, 35 nmol muscimol, or 4 nmol dicentrine into unilateral paraventricular nucleus, respectively. Rats in the control group (WKY1) and experimental group (SHR1) were compared for the GABA effect on blood pressure (MAP), heart rate (HR), and arterial baroreceptor reflex function (BRS) changes under waking state. Anesthetic WKY rats (WKY2) and spontaneously hypertensive rats (SHR2) were compared for the GABA effect on those abovementioned indexes. Abdominal aorta mean arterial pressure, heart rate, and arterial baroreceptor reflex function changes were compared in all rats. RESULTS: MAP, HR, and BRS were slightly lower in the rats under anesthetic state than in waking state before treatment (P < 0.05); they did not show significant changes between anesthetic and waking state, however, after treatment (P > 0.05). Unilateral paraventricular nucleus injection of GABA or muscimol elevated MAP, HR, and BRS in both normal and spontaneously hypertensive rats under waking or anesthetic state (P < 0.05). In addition, the amplitudes of changes of three indicators in spontaneously hypertensive group were markedly higher than those of control group (P < 0.05). Dicentrine could induce MAP and HR to increase, while BRS decreased significantly (P < 0.05). The amplitudes of changes in spontaneously hypertensive group were larger than those of normal group (P < 0.05). CONCLUSION: Centrally GABA injection can enhance the BRS function in spontaneously hypertensive rats and adjust heart rate to reduce the blood pressure fluctuation. It may play a role in reducing blood pressure and protecting cardiovascular function. PMID- 26550414 TI - Effects of the intermittent injection with super-low pressure on the postoperative pain control during the uterine artery embolization for uterine myoma. AB - OBJECTIVE: Uterine artery embolization (UAE) has been commonly used for uterine myoma with satisfactory effects, but the pain during and following the procedure with an occurrence rate in 100%. The aim of this study was to observe the effects of intermittent injection with super-low pressure on pain control during the UAE for uterine myoma. METHODS: 67 subjects were divided into 2 groups with 47 in group A and 20 in group B. A underwent UAE with the intermittent injection at super-low pressure, while B underwent routine UAE. Pain was assessed according to WHO analgesic ladder. Meanwhile, all were scored with the visual analogue scale (VAS). RESULTS: The numbers of first, second and third step analgesic user in Group A were 21, 18 and 6, respectively, with 2 non-analgesic users, while in Group B were 4, 6 and 10, respectively without non-analgesic user (chi-square = 7.043, P = 0.008). VAS showed good pain control in 23 cases, satisfactory in 18 and poor in 6 in Group A, while in Group B, were 4, 8 and 8, respectively (chi square = 7.329, P = 0.007). Mean follow-up was 16.5 months (range, 6-32 months). The abnormal menstruation was improved and the ultrasound examination 6 months later demonstrated a significant decrease in the diameter of myoma (from 6.65 +/- 2.40 cm to 5.22 +/- 1.86 cm, t = 3.186, P = 0.002). CONCLUSION: The application of intermittent injection with super-low pressure during UAE can decrease and possibly eliminate post-operative pain. But the procedure time was increased. PMID- 26550415 TI - Impacts of phosphatase and tensin homology deleted on chromosome ten (PTEN) inhibiting chitosan scaffold on growth and differentiation of neural stem cells. AB - OBJECTIVE: The aim of this study was to investigate growth and differentiation of neural stem cells (NSCs) on the phosphatase and tensin homology deleted on chromosome ten (PTEN)-inhibitor-adsorbed chitosan scaffold. METHODS: NSCs were divide into the chitosan group and the control groups, and performed CCK-8 test on 1(st), 3(rd) and 7(th) d to compare the proliferation between the 2 groups. The chitosan scaffold adsorbed PTEN inhibitor bpv (pic), and the empty scaffold was used as the control for co-culture of NSCs, immunofluorescence staining was performed on 7(th) d to detect the differentiation of NSCs on the scaffold. RESULTS: The results of CCK-8 test showed no significant difference in the absorbance between the 2 groups. Immunofluorescence staining showed that the NSCs numbers of the bpv scaffold group were more than the empty scaffold group, among which the anti-glial fibrillary acidic protein (GFAP) positive cells were less than the empty scaffold group, while the anti-beta-Tubulin III positive cells were more than the empty scaffold group, the two groups both showed rare anti receptor-interacting protein (RIP) positive cells. CONCLUSIONS: Chitosan scaffold exhibited good compatibility to NSCs, the PTEN-inhibitor-adsorbed chitosan scaffold could promote the migration of NSCs towards the scaffold and their differentiation towards neurons. PMID- 26550416 TI - Lycopene attenuates early brain injury and inflammation following subarachnoid hemorrhage in rats. AB - Early brain injury (EBI), following subarachnoid hemorrhage (SAH), includes blood brain barrier (BBB) disruption and consequent edema formation. This study aims to evaluate the effect of lycopene on early brain injury and inflammation in SAH. Neurological deficits, brain water content and Evans blue dye extravasation were evaluated after the treatment with lycopene. Besides neuronal apoptosis,some inflammatory cytokines were also detected. The results suggested that administration of lycopene following SAH significantly ameliorated EBI, including brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In addition, it also ameliorated inflammation triggered by SAH. In conclusion, post-SAH lycopene administration may attenuate EBI in SAH, possibly through ameliorating neuronal apoptosis, maintaining BBB integrity and attenuating inflammation. PMID- 26550417 TI - Expression of Toll-like receptor 4 in ovarian serous adenocarcinoma and correlation with clinical stage and pathological grade. AB - Toll-like receptor 4 (TLR4) plays an essential role in adaptive and innate immunity, and its expression has been described in various tumors. This study aimed to examine the expression of TLR4 in serous tumors and to evaluate its correlation to clinicopathological parameters. The expression of TLR4 was immunohistochemically examined in 63 species of normal ovarian epithelia and 336 species of serous epithelial lesions. Moreover, the association between TLR4 expression and various clinicopathologic features was assessed. The expression intensity of TLR4 in benign and borderline to malignant ovarian tumours showed a gradual rising trend. We identified positive correlations between TLR4 expression levels and both FIGO stage and pathological stage. In serous adenocarcinoma, TLR4 expression levels were significantly associated with chemoresistance. There was no relationship between the expression of TLR4 and the patient's age or pretreatment serum CA125 levels. Our data suggest that TLR4 might stimulate serous ovarian carcinoma initiation and progression. TLR4 expression is correlated with poor chemoresponse, which has important implications for the development of new therapeutic strategies for drug-resistant ovarian cancer. PMID- 26550418 TI - Efficacy and safety evaluation of intra-articular injection of tranexamic acid in total knee arthroplasty operation with temporarily drainage close. AB - OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) injection during primary total knee arthroplasty (TKA) for reducing postoperative hemorrhage. METHODS: 100 cases of patients admitted to our hospital and underwent primary unilateral TKA from January 2012 to December 2014 were enrolled in this study and they were divided randomly into two groups. For the TXA group, 1 g TXA was dissolved in 50 ml 0.9% sodium chloride solution and injected after prosthesis implantation but before cavity close. Conventional drainage clamping was carried for 4 h and the drainage tube was removed 48 h postoperative. For the control group, similar measures were taken except for that no TXA was dissolved in 0.9% sodium chloride solution. Postoperative hemoglobin, blood coagulation index, total blood loss volume, drainage volume, blood transfusion rate and lower extremity deep vein thrombosis (DVT) rate in both groups were observed and the efficacy and safety of this surgical treatment were evaluated. RESULTS: There were no significant differences in operation time, postoperative platelet and APPT, D-dimer, lower limb venous thrombosis incidence rate 1 week after operation between the two groups. Postoperative drainage volume, hemoglobin, total blood loss and blood transfusion rate in the TXA group were significantly lower than those of the control group. Ecchymosis of lower extremity peripheral incision and its surroundings was significantly milder than that of the control group. CONCLUSION: Intraoperative intra-articular injection of TXA in TKA can significantly reduce the initial postoperative hemorrhage and blood transfusion rate at the early stage after operation. PMID- 26550419 TI - Little association between the interleukin 10-3575T/A polymorphism and cancer risk: pooled analysis of 15608 cancer cases and 17539 controls. AB - The aim of the present work was to evaluate the association between the interleukin 10 (IL-10) -3575T/A (rs1800890) polymorphism and cancer risk. We performed a met-analysis based on 15 studies, including 15608 cancer cases and 17539 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association, and performed sensitivity analyses. In the stratified analyses by all included studies, no association between IL-10 3575T/A (rs1800890) polymorphism and cancer risk (OR=0.966, 95% CI=0.889-1.05, P=0.417 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.257 for AA vs. AT+TT; OR=1.008, 95% CI=0.964-1.054, P=0.723 for AA+AT vs. TT) was observed. In the stratified analyses by cancer type of lymphoma and non-lymphoma, no association between them was also detected (Lymphoma: OR=1.021, 95% CI=0.962-1.083, P=0.496 for A vs. T; OR=1.029, 95% CI=0.967-1.095, P=0.363 for AA vs. AT+TT; OR=1.017, 95% CI=0.952-1.086, P=0.626 for AA+AT vs. TT; Non-lymphoma: OR=0.966 95% CI=0.889 1.51, P=0.245 for A vs. T; OR=1.035, 95% CI=0.975-1.1, P=0.287 for AA vs. AT+TT; OR=1.017, 95% CI=0.948-1.091, P=0.967 for AA+AT vs. TT). The results were the same by sensitivity analyses. No publication bias was existed in the analysis. The interleukin 10-3575T/A polymorphism may have no association with cancer risk. PMID- 26550420 TI - Association of tea consumption and the risk of thyroid cancer: a meta-analysis. AB - OBJECTIVES: Epidemiological studies evaluating the association of tea consumption and the risk of thyroid cancer risk have produced inconsistent results. Thus, we conducted a meta-analysis to assess the relationship between tea consumption and thyroid cancer risk. METHODS: Pertinent studies were identified by a search in PubMed and Web of Knowledge. The random effect model was used based to combine the results. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Finally, 11 articles with 14 studies (2 cohort studies and 12 case control studies) involving 2,955 thyroid cancer cases and 106,447 participants were included in this meta-analysis. The relative risk (95% confidence interval) of thyroid cancer for the highest versus the lowest category of tea consumption was 0.774 (95% CI = 0.619-0.967), and the associations were also significant in Europe and America, but not in the Asia. No publication bias was found. CONCLUSIONS: Our analysis indicated that higher tea consumption may have a protective effect on thyroid cancer, especially in Europe and America. PMID- 26550421 TI - miR-29a promotes myocardial cell apoptosis induced by high glucose through down regulating IGF-1. AB - This study was aimed to investigate the role of miR-29a in myocardial cell apoptosis induced by high glucose. Myocardial cells were cultured in normal (5.6 mmol/l) or high glucose medium (30 mmol/l). The apoptotic rate of myocardial cells was evaluated using flow cytometry. The mRNA levels of Bax, Bcl-2, miR-29a, and IGF-1 were determined using real-time quantitative PCR (RT-qPCR). The level of IGF-1 in the culture medium was analyzed using enzyme-linked immunosorbent assay (ELISA). The interaction sites between miR-29a and IGF-1 was analyzed using the the Targetscan program. The regulatory effect of miR-29a on the expression of IGF-1 was investigated using dual luciferase reporter system. The results showed that the expression of miR-29a and the Bax/Bcl-2 ratio in myocardial cells were significantly increased after the cells were cultured in high glucose medium for 72 h, which was consistent with increased apoptosis of myocardial cells. The expression of IGF-1 in myocardial cells was significantly decreased after the cells were cultured in high glucose medium for 72 and 96 h. Targetscan identified a potential binding site on the 3'-UTR of IGF-1 for miR-29a. We also observed that miR-29a mimic and miR-29a inhibitor reduced and increased the expression of IGF-1 in myocardial cells cultured in high glucose medium, respectively. Dual luciferase reporter analysis showed that miR-29a significantly reduced the fluorescence intensity of wild-type psichek2-IGF-1-3'UTR-WT but the fluorescence intensity of mutant psichek2-IGF-1-3'UTR-MT was not significantly affected. In conclusions, the expression of miR-29a in myocardial cells cultured in high glucose medium was significantly increased, which down-regulated IGF-1 and increased myocardial cell apoptosis. PMID- 26550422 TI - One-stent versus two-stent techniques for distal unprotected left main coronary artery bifurcation lesions. AB - OBJECTIVE: To assess the clinical outcomes of percutaneous coronary intervention (PCI) with single-stent versus double-stents implantation in distal unprotected left main coronary artery (ULMCA) bifurcation lesions and evaluate their merits and demerits in this clinical setting. METHODS: 88 patients with distal ULMCA bifurcation lesions and treated with PCI with single or double stents implantation (50 in the one-stent group and 38 in the two-stent group) was included. RESULTS: No significant difference in the number of left main and multivessel disease, stenosis rate of left main, inner diameter of left main vessel, and distal bifurcation angle was noted. The procedural success rate was 100%. Single-stent group had significantly lower ostial residual stenosis of left anterior descending and higher ostial residual stenosis of left circumflex as compared to double-stent group. During the hospitalization period, no major adverse cardiovascular events were observed in the two groups. During the follow up period, restenosis was observed in 1 case in single-stent group and in 2 cases in double-stent group, respectively. Recurrence of angina and target lesion revascularization was observed in 6 and 1 case in single-stent group, and 4 and 2 cases in double-stent group, respectively. There was no acute myocardial infarction, in-stent thrombosis and cardiac death in both of the groups. CONCLUSIONS: Both stenting strategies were feasible for distal ULMCA bifurcation lesions with a high operation success rate and safety. Single-stent technique had lower ostial residual stenosis of left anterior descending whereas double-stents technique had lower ostial residual stenosis of left circumflex. PMID- 26550423 TI - Comparison of two kinds of cutaneous ureterostomy using in radical cystectomy. AB - OBJECTIVE: To investigate the merits and 10 year follow-up results of two kinds of cutaneous ureterostomy operation in patients with the radical cystectomy. METHODS: We retrospective analyzed the information of patients underwent radical cystectomy in the past 10 years, comparing and analyzing the consequence of application value, early and long-term follow-up results using two kinds of cutaneous ureterostomy in patients with radical cystectomy. RESULTS: Unilateral ureteral cutaneous ureterostomy didn't increase patients' early and long-term complications, and improved the patient's life satisfaction. CONCLUSION: The unilateral cutaneous ureterostomy didn't increase postoperative complications in patients, while improving the patient's life satisfaction. Unilateral ureteral cutaneous ureterostomy is an important complement to urinary diversion after radical cystectomy and the best choice for cutaneous ureterostomy. PMID- 26550424 TI - Clinical comparison of percutaneous coronary intervention with domestic drug eluting stents versus off pump coronary artery bypass grafting in unprotected left main coronary artery disease. AB - OBJECTIVE: The aim of our study was to compare the clinical outcomes of percutaneous coronary intervention (PCI) with domestic drug-eluting stents (DES) and off pump coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery (ULMCA) disease. METHODS: A total of 227 patients with ULMCA disease and underwent revascularization was included. One hundred and six patients were treated with PCI with domestic DES implantation and 121 patients with off pump CABG. Clinical outcomes with respect to the major adverse cardiovascular and cerebrovascular events (MACCE) including death any cause, non-fatal myocardial infarction (MI), stroke, and target vessel revascularization (TVR) during hospitalization and at 12-month follow-up were recorded. RESULTS: There was no significant difference between the domestic DES and off pump CABG groups in the risk of death, non-fatal MI, stroke, and TVR during hospitalization and at 12-month follow-up. Overall in-hospital MACCE in PCI versus CABG was 0.94% versus 5.78% (P<0.05). The overall MACCE at 12-month follow up in PCI versus CABG was in 3.77% versus 3.31% (P>0.05). CONCLUSIONS: Domestic DES is feasible and safety in the treatment of ULMCA lesions. When compared with off-pump CABG, domestic DES achieved similar completeness of revascularization, similar in-hospital and 12-month follow-up outcomes. A longer follow-up is needed. PMID- 26550425 TI - Correlation between GDF 15 gene polymorphism and the collateral circulation in acute non-ST segment elevated myocardial infarction. AB - OBJECTIVE: To investigate the correlation between growth differentiation factor 15 (GDF 15) + 157 A/T polymorphism and the formation of collateral circulation in acute non-ST segment elevated myocardial infarction in Han population of Shandong province. METHOD: The medical records of 200 cases of patients undergoing selective coronary angiography were analyzed, and the arterial blood specimens of included patients were collected before coronary angiography. Based on the results of coronary angiography, patients were divided into acute myocardial infarction (AMI) group and normal control group; AMI group was divided into collateral group and non-collateral group by Rentrop's grading method; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to analyze the GDF 15 + 157 A/T polymorphism in the two groups. RESULTS: There were statistically significant differences in GDF 15 + 157 A/T AA and AT distribution between AMI group and the control group (P = 0.002); and there was statistically significant difference in allele frequencies between the two groups (P = 0.006); for AMI group, there were statistically significant differences in GDFAA and AT genotype distribution between patients with and without collateral (P = 0.014), and there was statistically significant difference in allele frequencies between the two (P = 0.025). CONCLUSION: There was correlation between GDF 15 + 157 A/T polymorphism and the formation of collateral circulation in patients with non-ST-segment elevated myocardial infarction. PMID- 26550426 TI - Preparation and antitumor effects of glaucocalyxin A-gamma-cyclodextrin clathrate. AB - OBJECTIVE: To improve the water solubility of glaucocalyxin A (GLA) by the preparation of glaucocalyxin A gamma-cyclodextrin clathrate (GLA-gamma-CD) and to investigate the inhibitory effect of GLA-gamma-CD on tumor growth in S180 cell xenografts. MATERIALS AND METHODS: GLA-gamma-CD, gamma-cyclodextrin (gamma-CD) and GLA were combined at a mass ratio of 1:1, dissolved in 60 degrees C water by stirring. GLA completely entrapped by the gamma-CD was verified by differential thermal analysis, the GLA content was determined. Phase solubility, solubility, and in vitro dissolution rate experiments were performed. The S180 xenograft mouse model was used to observe the tumor inhibitory effects of GLA-gamma-CD and GLA, and the TUNEL assay was used to detect differences in their rates of tumor cell apoptosis induction. RESULTS: After combination with gamma-CD, the solubility of GLA-gamma-CD was 21.78-fold greater than that of GLA. The in vitro dissolution rate of GLA-gamma-CD was significantly greater than that of GLA, and reached more than 90% in 20 min. Furthermore, GLA-gamma-CD was more effective than GLA as an inhibitor of S180 tumor cells; the inhibitory rate of the high dose group reached 57.26%, which was 54.11% greater than the inhibitory rate of the GLA group at the same dose. In addition, GLA-gamma-CD induced tumor cell apoptosis more effectively than did GLA. CONCLUSION: The water solubility of GLA significantly increased in combination with gamma-CD resulting in the production of GLA-gamma-CD. Furthermore, GLA-gamma-CD was more effective than GLA as an inducer of S180 tumor cell apoptosis and an inhibitor of tumor growth. PMID- 26550428 TI - Effect of RhoA gene silencing on proliferation and migration of gastric MGC-803 cells. AB - In this study, the expression of silencing RhoA gene in gastric MGC-803 Cells was investigated, in order to discuss the effect of RhoA gene on cell proliferation, cell cycles and tumor migration. SiRNA sequence of RhoA gene was designed and synthesized; MGC-803 cells were transfected by Lipofectamine(TM2000). The expression of RhoA gene in mRNA and protein after interference was detected by RT PCR and Western blot; flow cytometry was used to detect the cell cycle; cell proliferation was detected by CCK-8 assay and cell migration was detected by scratch healing assay. RhoA expression in mRNA and protein of the experimental group was significantly lower than that of the control group and blank group, and the difference was statistically significant (P < 0.05). The growth rate significantly slowed down in experimental group; the cell cycle was arrested in the G0/G1 phase and the number of cells in S-phase reduced; there was a statistically significant difference (P < 0.05). Scratch healing assay showed that cell migration of the experimental group was significantly decreased, with a statistically significant difference (P < 0.05). Specific interference on RhoA gene expression could inhibit the proliferation and migration of MGC-803 cells; therefore, siRNA sequences of RhoA gene may be an effective target for the treatment of gastric cancer. PMID- 26550427 TI - Efficacy of rutin in inhibiting neuronal apoptosis and cognitive disturbances in sevoflurane or propofol exposed neonatal mice. AB - Sevoflurane and propofol are widely used in pediatric anesthesia. Neurotoxicity of sevoflurane and propofol in developing brain has been reported and these effects raise concerns on the usage of the drugs. We investigated the influence of rutin, a flavonoid on the neurodegenerative effects of sevoflurane and propofol and on memory and cognition in neonatal rodent model. Separate groups of neonatal mice (C57BL/6) were administered with rutin at 25 or 50 mg/kg body weight (b.wt) from post natal day 2 (P1) to P21. P7 mice were exposed to 2.9% sevoflurane and/or propofol (150 mg/kg b.wt). Neuroapoptosis was assessed by measuring activated caspase-3 and by Fluoro-Jade C staining. Plasma S100beta levels were detected by ELISA. Morris water maze test was performed to test learning and memory impairments in the animals. General behaviour of the mice was also assessed. Anesthesia exposure caused severe neuroapoptosis and also raised the levels of plasma S100beta. Neuroapoptosis, memory and cognitive deficits observed following anesthetics were comparatively more profound in mice on exposure to combined drug (sevoflurane and propofol) than in those exposed to either of the anesthetics. Rutin at both the doses was effective in reducing the apoptotic cell counts and enhanced the memory and cognitive abilities. Rutin supplementation offered significant protection against anesthetic induced neurodegeneration and learning and memory disturbances. PMID- 26550429 TI - Diagnosis efficiency for pulmonary embolism using magnetic resonance imaging method: a meta-analysis. AB - PE (Pulmonary embolism, PE) is a common disease, usually caused by blockage of pulmonary artery and its branches due to exogenous or endogenous embolic obstruction. PE always be misdiagnosed in clinical. The aim of this study is to calculate the sensitivity and specificity of magnetic resonance imaging (MRI) in assessing the resectability of PE. In this study, a meta-analysis of the reported sensitivity and specificity of each study with 95% confidence intervals (CI) was performed. Five studies were included in the meta-analysis. The results indicated that the quality assessment scores ranged from 11 to 13, with a mean study quality score of 12. The sensitivity and specificity values including 95% CI at the patient level were calculated. The sensitivities ranged from 78% to 100%, and the specificity ranged from 99% to 100%. The pooled sensitivity value including 95% CI was 0.83 (0.78-0.88), and with inconsistency (I (2)) of 62.8%. The pooled specificity value including 95% CI was 0.99 (0.98-1.00), with inconsistency (I(2)) of 0.0%. Pooled positive likelihood ratio (PLR) (95% CI) was 70.22 (29.04 169.76), and the pooled negative likelihood ratio (NLR) (95% CI) was 0.19 (0.14 0.25). The overall diagnostic odds ratio (DOR) (95% CI) was 448.98 (163.47 1233.18). The summary receiver operating characteristic (SROC) data illustrated that the area under the curve (AUC) was 0.9852. In conclusion, the MRI method may be acts as a potential and assistant method for the PE diagnosis. PMID- 26550430 TI - Calcium intake and hip fracture risk: a meta-analysis of prospective cohort studies. AB - It has been suggested that the amount of calcium intake may influence hip fracture incidence. However, the results of the researches in this regard are inconsistent. We performed this meta-analysis to estimate the association between calcium intake and hip fracture risk. Prospective cohort studies on calcium intake and hip fracture risk were identified by searching databases from the period 1960 to 2014. Results from individual studies were synthetically combined using STATA 11 software. The results indicated that a total of 8 prospective cohort studies were included in our meta-analysis, involving 2,435 cases and 267,759 participants. The combined relative risk (RR) of hip fracture for highest compared with lowest amount calcium intake was 0.97 (95% confidence interval [CI]: 0.89-1.07). Little evidence of publication bias was found. In conclusion, this meta-analysis provides evidence of no association between calcium intake and hip fracture risk. However, this finding is based on only a limited number of included studies. PMID- 26550431 TI - Plumbagin shows anticancer activity in human osteosarcoma (MG-63) cells via the inhibition of S-Phase checkpoints and down-regulation of c-myc. AB - OBJECTIVE: Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae), has been extensively studied for its pharmacological activities and reported to show a good anti-cancer activity in different human cancer cell lines. It is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. Plumbagin is also known to inhibit NF-kappaB, JNK (Hsu), PKCepsilon, and STAT-3. However, the anti-proliferatory activity and their core molecular mechanisms have been poorly determined. METHODS: Human osteosarcoma (MG 63) cells were exposed to plumbagin and the anti-proliferative activity was evaluated by MTT assay. The mechanism of action for the growth inhibitory activity of plumbagin on MG-63 cells was evaluated using flow cytometry for cell cycle distribution, and western blot for assessment of accumulation and phosphorylation of potential target proteins. Furthermore, morphology of MG-63 cells was assessed after treatment with Plumbagin. RESULTS: Plumbagin has significantly induced growth inhibition against osteosarcoma MG-63 cells, primarily by S-phase cell cycle arrest which is confirmed by the down regulation of cyclin A and CDK2 protein levels determined by western blot analysis. It was also found that plumbagin has triggered the DNA damage in MG-63 cells, subsequently initiating the arrest in S-phase, which is evident by the up regulation of phosphorylated p53 and histone. Furthermore, plumbagin resulted in the down-regulation of c-myc protein expression in the MG-63 cells. CONCLUSION: Plumbagin has triggered DNA damage and had induced S-phase arrest in MG-63 cells, suggesting it to be a potential compound in treatment against malignant human osteosarcoma. PMID- 26550432 TI - Conchal compression: is it a new syndrome? AB - OBJECTIVES/HYPOTHESIS: To describe the diagnostic criteria and treatments of concha compression syndrome (CCS). PATIENTS AND METHODS: Patients who reported at least 3 times rhinosinusitis attacks per year were considered in this study. All patients met the diagnosis criteria of rhinosinusitis based on clinical history, showed a nasal septal spur compressing concha on their endoscopic examination and had no findings of rhinosinusitis on their paranasal sinus CT scans but showed concha ondularis. These patients were recognized as suffering from CCS and consequently were surgically treated. RESULTS: 85 patients diagnosed with CCS were included in this study. 25 of the patients were classified as middle, 53 as inferior and 7 as both middle and inferior CCS. Septal spur removal was performed on 16 of the patients whereas the remaining 69 patients received spur removal with septoplasty. After surgery, most of patients' symptoms improved clinically. CONCLUSION: The importance and the necessity of further investigations into this newly-defined syndrome in the differential diagnosis of rhino-neurogenic symptoms is made clear by this study. PMID- 26550433 TI - Exogenous hTERT gene transfected endothelial progenitor cells from bone marrow promoted angiogenesis in ischemic myocardium of rats. AB - OBJECTIVE: To explore the biological behavior and the revascularizative ability of endothelial progenitor cells (EPCs) transfected with human telomerase reverse transcriptase (hTERT) gene. METHODS: EPCs were isolated from mononuclear cells in bone marrow by using the method of density gradient centrifugation, then cultured with differential velocity adherent method, EPCs were transfected by recombinant plasmid carrying GFP report gene EGFP-hTERT. The EPCs secretion and proliferation ability were detected before and after transfection. The expression of EPCs mRNA were detected by RT-PCR before and after transfection. The new capillaries of infarct area were observed. RESULTS: After transgenesis, the proliferation of EPCs were increased, and the secretion of NO, LDH, iNOS by EPCs were significantly increased compared to the non-transgenesis group. After transplanted the transfected EPCs into the ischemic myocardial of rats, revascularization were increased obviously. CONCLUSION: EPCs maintained the original biological characteristics after transfecting exogenous hTER gene, the proliferation and survival rate were up-regulated significantly, and the revascularization ability of EPCs were significantly strengthen. PMID- 26550434 TI - Successful single-lung ventilation using a bronchial occluder for repair a large tracheoesophageal fistula: a case report. AB - A 25-year-old girl was found a large tracheoesophageal fistula (TEF) 20 cm away from the incisors by gastroscope. It was a consequence of prolong intubation after the head operation because of right temporal lobe cerebral hemorrhage broken into ventricles. The patient was tracheotomy and retained spontaneous breathing. Operation was planned to via cervical and thoracic abdominal esophageal transection plus cervical esophagogastrostomy to repair the fistula under single lung ventilation under general anesthesia. Here we report a successful case using an endotracheal tube (EET) combine with a bronchial occluder for single ventilation to repair a large TEF. PMID- 26550435 TI - Treating heterogeneous emphysema by lung volume reduction surgery using one-way valve stent implantation. AB - PURPOSE: To retrospectively analyze the efficacy and complications of lung volume reduction surgery (LVRS) using one-way valve stent implantation in three heterogeneous emphysema cases. METHODS: We performed bronchoscopic, lung CT, pulmonary function (PF) and 6-minute walk distance (6MWD) tests respectively before operation and 1 month, and 3 and 6 months after operation to estimate the surgical effects in the 3 cases by comparing the test results. RESULTS: After operation, all the three cases had worsened symptoms of cough and expectoration; two of them had hemoptysis, EVB-related infections and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), one of them had airway distortion and respiratory failure and still one of them had granulation hyperplasia. Postoperative reexamination results revealed that one patient had obviously increased forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and 6-minute walk distance (6MWD) and right upper pulmonary atelectasis, but no apparent improvements in FEV1, FVC, and 6MWD were found in the other two patients. CONCLUSIONS: The patient with postoperative pulmonary atelectasis was found with significantly improved PF at the first month after surgery, but the PFs thereof had a drop at the sixth month after surgery due to EVB-related infections. No obvious improvements in the PFs of all the three patients were observed in the reexamination performed six months after surgery. The long-term effects of LVRS with one-way valve stent implantation are uncertain, and further studies should be carried out in the future. PMID- 26550436 TI - Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5. AB - BACKGROUND: Notch signaling is indicated as novel therapeutic targets to prevent recurrence of breast cancer. LncRNAs were identified as downstream target of Notch pathway. However, the exact mechanisms involved in Notch signaling, lncRNAs and breast cancer remain to be explained. OBJECTIVE: This original research aimed to determine the prognostic implications of Notch-1 for breast cancer, and explain mechanisms involved in regulation of lnRNA GAS5 by Notch-1, and identify the function of this mechanism on breast cancer. METHOD: Thirty breast cancer patients were included from The First Affiliated Hospital of Anhui Medical University (China) since January 2006 in this study. The mRNA level by RT-PCR and protein level of Notch-1 by western blot in tumor tissues and adjacent normal tissues were evaluated and 5-year survival analysis was applied to examine the significance of Notch-1. The levels of ten reported lncRNAs were determined by RT PCR, and subsequently linear analysis was applied to analyze the relationship between these four unique lncRNAs and protein level of Notch-1, which identified the most relevant lncRNA GAS5 with Notch-1 in breast cancer. Subsequently, Notch1 siRNA was applied to influence the expression of Notch-1 in T47D, then the level of RSA5 was measured by RT-PCR, and CCK-8 assay was applied to measure the proliferation of T47D cells. RESULTS: High level of Notch-1 provided a poor prognosis in breast cancer. Interference of Notch-1 significantly suppressed proliferation of T47D cell (P < 0.05), and significantly increased the level of GAS5. CONCLUSION: Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5. PMID- 26550437 TI - Retaining of PTCA guide wire in the left ventricular lead and subsequent application of epicardial electrode when CRT-D implantation in a patient with severe heart failure and persistent left superior vena cava: a case report. AB - OBJECTIVE: One patient with severe heart failure (LV 92 mm, EF 28%) was treated by cardiac resynchronization therapy (CRT). METHOD: During the operation, it was found that double superior vena cava coexisted, and selective coronary venography cannot clearly show every branch. It was difficult to push ventriculus sinister electrode to sideward vein, so the electrode was released to far end of frontal septal branch along great cardiac vein. RESULT: However, because of insufficient braced force of ventriculus sinister electrode, 0.014 PTCA guide wire was detained in the electrode. 2 years later, two spots of PTCA guide wire retained in ventriculus sinister electrode broke in atrium dextrum, so the implantation of epicardial electrode was conducted. CONCLUSION: After the operation, heart failure was relieved. After 43 months, the battery of pacemaker depleted, so the pacemaker was changed. The effect since follow-up visit was good, LV decreased to 86 mm, EF increased to 32%, and SPWMD time limit shortened from 147 ms to 45 ms. The therapeutic experience of this patient indicated that the effect of detaining PTCA guide wire to enhance braced force in implantation of ventriculus sinister is unreliable and inappropriate to be advocated. PMID- 26550438 TI - Predictive value of microRNAs as novel biomarkers in detection of lymphoma. AB - MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks' funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application. PMID- 26550439 TI - Efficiency of high-frequency oscillatory ventilation combined with pulmonary surfactant in the treatment of neonatal meconium aspiration syndrome. AB - The aim of this study was to investigate the clinical efficiency of the use high frequency oscillatory ventilation (HFOV) combined with pulmonary surfactant (PS) for the treatment of neonatal meconium aspiration syndrome (MAS). Clinical data of 53 MAS patients admitted to neonatal intensive care unit (NICU) was collected and the patients were divided into 3 groups according to the different treatment approach: group 1 conventional mechanical ventilation (CMV); group 2 HFOV; group 3 HFOV + PS. By monitoring the changes in oxygenation function indicators such as inhaled oxygen concentration (FiO2), oxygenation index (OI) and arterial oxygen tension/alveolar arterial oxygen tension (a/ApO2) of three groups after 2, 12, 24, 48 h of treatment, the usage of the ventilator, duration of hospitalization, changes in clinical manifestations and outcomes of three groups were analyzed. As compared to group 1, the difference in all the oxygenation function indicators after treatment in group 2 and group 3 was statistically significant at different points in time (P < 0.05). However, the timing and extent of the change in the indicators in group 3 were more significant than in group 2; as compared to group 1, the ventilation time, duration of the oxygen therapy and hospitalization time of group 2 and group 3 were significantly shorter and the difference was statistically significant (P < 0.05). Early use of HFOV combined with PS to treat MAS has significant therapeutic effect, especially for the treatment of severe MAS where it can be used as a safer and more effective rescue measure. PMID- 26550440 TI - Ginsenoside Rd mitigates myocardial ischemia-reperfusion injury via Nrf2/HO-1 signaling pathway. AB - Ginsenoside Rd (GsRd) reportedly protects the heart against ischemia-reperfusion (I/R) injury. Nrf2/HO-1 signaling plays a key role in attenuating oxidative stress. However, it remains unclear whether GsRd protects against myocardial I/R injury via Nrf2/HO-1 signaling. This study aimed to investigate the role of Nrf2/HO-1 signaling in the cardioprotective effect of GsRd. Rats received 30 min ischemia followed by 2 h reperfusion. Cardiac function, infarct size and serum CK, LDH, cTnI levels were detected. The expression of Nrf2 and HO-1 was detected by western blot. The results suggested that GsRd attenuated myocardial I/R injury as evidenced by improved cardiac function, decreased infarct size and decreased levels of serum CK, LDH and cTnI. In addition, GsRd administration enhanced the expression of Nrf2 and HO-1. In conclusion, the present study shows that GsRd protects against myocardial I/R injury via Nrf2/HO-1 signaling. PMID- 26550441 TI - Early acetabular cartilage degeneration in a rabbit model of developmental dysplasia of the hip. AB - BACKGROUND: Mild developmental dysplasia of hip (DDH) causes high morbidity of osteoarthritis (OA) on adult. It is thought that change of collagen and proteoglycans in cartilage may be the direct reasons for osteoarthritis. OBJECTIVE: To detect the changes of the expressions of type II collagen of acetabular cartilage in early DDH and to investigate the relevance between type II collagen and the degeneration mechanism of the acetabular cartilage. METHODS: The rabbit model of DDH was successfully established by applying the method of knee extending and fixing with cylinder cast in which left lower extremity as experimental group and right one as control group, checking with X-ray after 5 weeks. The stains of H&E and toluidine blue were applied on the samples of acetabular cartilage to observe the morphological changes of chondrocytes and extracellular matrix (ECM). The immunohistochemical staining and Western-blot were employed to respectively qualify and quantitate the expression of type II collagen. RESULTS: Pathohistology observing indicated the signs of retrogressive changes of acetabular cartilage in experimental group. Also, the positive stained cells in type II collagen in experimental group was higher based on immunohistochemiscal staining. The quantitative amounts of type II collagen by Western-blot in experimental group was higher significant difference existed between two groups (t = 2.18, P < 0.05). CONCLUSIONS: The expression of type II collagen is correlated to a degeneration of acetabular cartilage and increase obviously in early DDH. PMID- 26550442 TI - Cardioprotective effect of berberine against myocardial ischemia/reperfusion injury via attenuating mitochondrial dysfunction and apoptosis. AB - Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptischinensis, has been shown to display a wide range of pharmacological effects. The present study aims to investigate the effect of berberine on myocardial ischemia/reperfusion. Sixty male Sprague-Dawley rats were randomized equally into three groups: sham group, IR group, IR + berberine group. Rats were treated with berberine for 4 weeks and then I/R was performed. Myocardial infarction area was measured. Serum levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) were assayed. Myocardial apoptosis was detected by terminal dexynucleotidyltransferase (TdT) mediated dUTP nick end labeling (TUNEL). Mitochondrial function, including MMP and complex I activity, was assayed. Besides, the expression of Bcl-2, Bax and cytochrome c were detected by Western blot. Our results suggested that berberine decreased myocardial infarction area, and decreased serum levels of CK-MB, LDH and cTnI. Berberine attenuates myocardial apoptosis and improved mitochondrial dysfunction. Berberine up-regulates the expression of Bcl-2 and mitochondrial cytochrome c and down-regulates the expression of Bax and cytosolic cytochrome c. In conclusion, berberine protects the heart from ischemia/reperfusion injury via attenuating mitochondrial dysfunction and myocardial apoptosis. PMID- 26550443 TI - Clinical observations of supraventricular arrhythmias in patients with brugada syndrome. AB - OBJECTIVE: To study various types of supraventricular arrhythmias in patients with Brugada Syndrome. METHODS: Forty six patients with ECG of spontaneous type Brugada and with ventricular and/or supraventricular tachyarrhythmia, without structural heart diseases which were excluded by echocardiography, underwent 24 h Holter recording, electrophysiological study and/or radiofrequency ablation. RESULTS: There were thirty-nine male and seven female (mean age 37.44 years) among total forty-six patients. Twenty one patients had family histories of tachycardia, twentythree patients experienced episodes of syncope, and three patients were resuscitated from cardiac arrest. One patient had ventricular fibrillation and third degree atrioventricular block, eleven patients had polymorphic ventricular tachycardia and five patients had monomorphic ventricular tachycardia. Fourteen patients had atrial tachyarrhythmia, paroxysmal supraventricular tachycardia was found in five patients including four Wolf Parkinson-White syndrome, two patients hadventricular tachycardia and third degree atrioventricular block, one of them had atrial fibrillation, two patients had both supraventricular tachycardia and ventricular tachycardia, three patients had both atrial tachyarrhythmia and supraventricular tachycardia, two third degree atrioventricular block patients had atrial flutter, one patienthad both atrial tachyrhythmia and ventricular tachycardia. Radiofrequency blation was performed in thirty-nine patients and succeed in thirty-two, four patients were implanted with pacemakers, and four patients had implantable cardioverter defibrillators. CONCLUSION: In addition to ventricular tachycardia and ventricular fibrillation, patients with Brugada syndrome exhibit various supraventricular tachyarrhythmia and third degree atrioventricular block. In patients with Brugada syndrome, the dysfunction of the cardiac ion channel, which related to mutation of cardiac sodium channelgene, is not limited in His Purkinje system and ventricular myocardium, but also in the atrium and atrioventricular node, which may serves as a cause of dispersion of repolarization and phase 2 reentry leading to various arrhythmias. PMID- 26550444 TI - Meta-analysis of chemotherapy and dendritic cells with cytokine-induced killer cells in the treatment of non-small-cell lung cancer. AB - BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the most fatal cancers, which leads to large number of people dead. Followed by surgery, chemotherapy and radiotherapy, chemotherapy combined dendritic cells with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in NSCLC for some time, but little consistent beneficial results are provided. So, it is essential to weigh the pros and cons of the new therapeutic method. METHODS: We searched the randomized controlled trials of NSCLC mainly by PubMed database. Terms combination of "cytokine-induced killer cells", "tumor" and "cancer" were used. After evaluating the heterogeneity of selected studies, then we performed the meta-analysis. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed. RESULTS: Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P=0.02) and progression free survival (PFS) (P=0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P=0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P=0.21), 2-year PFS (P=0.10), overall response rate (ORR) (P=0.76) and partial response (PR) (P=0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest. CONCLUSIONS: Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients. PMID- 26550445 TI - CYP1B1 gene mutations with incomplete penetrance in a Chinese pedigree with primary congenital glaucoma: a case report and review of literatures. AB - To investigate the cytochrome P4501B1 (CYP1B1) mutations in a three-generation Chinese Han family with PCG, the 2 and 3 coding exons of CYP1B1 gene were amplified by PCR, and were directly sequenced using Sanger bidirectional sequencing reactions. The mutation c.517 G>A p.E173K was detected in all the affected individuals (which showed homozygous AA genotype) and not in all the unaffected ones except one individual. The mutation c.517 G>A p.E173K is associated with disease causing in this pedigree. And the possible genetic model is recessive inheritance. One apparently unaffected individual had mutations and haplotypes identical to her affected sibs suggested incomplete penetrance in this pedigree. PMID- 26550446 TI - Research on cultivating medical students' self-learning ability using teaching system integrated with learning analysis technology. AB - Along with the advancement of information technology and the era of big data education, using learning process data to provide strategic decision-making in cultivating and improving medical students' self-learning ability has become a trend in educational research. Educator Abuwen Toffler said once, the illiterates in the future may not be the people not able to read and write, but not capable to know how to learn. Serving as educational institutions cultivating medical students' learning ability, colleges and universities should not only instruct specific professional knowledge and skills, but also develop medical students' self-learning ability. In this research, we built a teaching system which can help to restore medical students' self-learning processes and analyze their learning outcomes and behaviors. To evaluate the effectiveness of the system in supporting medical students' self-learning, an experiment was conducted in 116 medical students from two grades. The results indicated that problems in self learning process through this system was consistent with problems raised from traditional classroom teaching. Moreover, the experimental group (using this system) acted better than control group (using traditional classroom teaching) to some extent. Thus, this system can not only help medical students to develop their self-learning ability, but also enhances the ability of teachers to target medical students' questions quickly, improving the efficiency of answering questions in class. PMID- 26550448 TI - Pterostilbene attenuates inflammation in rat heart subjected to ischemia reperfusion: role of TLR4/NF-kappaB signaling pathway [Retraction]. AB - [This retracts the article on p. 1737 in vol. 8, PMID: 25932102.]. PMID- 26550447 TI - Acute and subchronic toxicity as well as evaluation of safety pharmacology of traditional Chinese medicine "Huhezi". AB - The study was conducted to evaluate the toxicity and safety pharmacology of the traditional Chinese medicine, "Huhezi" granules. The results of acute toxicity test showed that the granules' LD50 was more than 5000 mg/kg, which indicated that the "Huhezi" belonged to actually non-toxic drug. Subchronic toxicity study showed that non-toxic reaction were detected in high (1000 mg/kg), medium (500 mg/kg) and low dose (250 mg/kg) of "Huhezi" groups by measuring rat body weight, organ coefficient, blood physiological indexes and blood biochemical indexes. Pathological examination showed that no tissue lesions were observed in test organs except liver (mild granular degenerationand reversible vesicular degeneration), spleen (Langerhans cells infiltrating) and kidney (homogeneous red staining of renal tubule). Safety pharmacology study found that "Huhezi" had no effects on the central nervous system, respiratory system and cardiovascular system. These results suggested that the dose of "Huhezi" at or below 1000 mg/kg through oral administration is considered safe. PMID- 26550449 TI - Quantitative functional MRI in a clinical orthotopic model of pancreatic cancer in immunocompetent Lewis rats. AB - OBJECTIVE: To demonstrate feasibility of performing quantitative MRI measurements in an immuno-competent rat model of pancreatic cancer by comparing in vivo anatomic and quantitative imaging measurements to tumor dissemination observations and histologic assays at necropsy. Meterials and methods: Rat ductal pancreatic adenocarcinoma DSL-6A/C1 cell line and Lewis rats were used for these studies. 10(8) DSL-6A/C1 cells were injected subcutaneously into the right flank of donor rats. Donor tumors reaching 10 mm were excised, and 1 mm(3) tumor fragments were implanted within recipient rat pancreas during mini-laparotomy. T1 weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced (DCE) MRI were performed using a Bruker 7.0T ClinScan. After MRI, all animals underwent autopsy. Primary tumor size was measured, and dissemination score was used to assess local invasion and distant metastasis. Primary tumor and all sites of metastases were harvested and fixed for H&E, Masson's trichrome, and rat anti CD34 staining. Trichrome slides were scanned and digitized for measurement of fibrotic tissue areas. Anti-CD34 slides were used for microvessel density (MVD) measurements. RESULTS: Primary tumors, local invasion, and distant metastases were confirmed for all rats. No significant differences were found between in vivo MRI measurements (48.7 +/- 5.3 mm) and ex vivo caliper measurements (43.6 +/ 3.6 mm) of primary tumor sizes (p > .05). Spleen, liver, diaphragm, peritoneum, and abdominal wall metastases were observed on MRI but smaller lung, mediastinum, omen, and mesentery metastases were only observed at necropsy. Contrast uptake observed during DCE measurements was significantly greater in both primary and metastatic tumor tissues compared to skeletal muscle and normal liver tissues. Both primary and metastatic tumors were hyper-intense in T2-weighted images and hypo-intense in T1-weighted images, but no differences were found between quantitative T2 measurements in primary tumors and that in metastases. Similarly, quantitative ADC measurements were similar for both primary tumor and liver metastases (1.13 +/- 0.3 * 10(-3) and 1.24 +/- 0.4 * 10(-3) mm(2)/s, respectively). Histologic fibrosis and MVD measurements were similar in primary tumors and metastases. CONCLUSIONS: Anatomic and quantitative functional MRI measurements are feasible in orthotropic DSL rat model and will permit non invasive monitoring of tumor responses during longitudinal studies intended to develop new interventional therapies for primary and metastatic disease. PMID- 26550450 TI - Adhesion: a confounding bias in murine cervical heterotopic heart transplantation. AB - Tissue adhesion is a common postsurgical phenomenon among the human population. This complication also occurs in murine transplant models. In this study, we investigated the impact of adhesion on murine cervical heterotopic heart transplantation by using sodium hyaluronate (SH) as an anti-adhesive agent. Our study revealed that SH administration produced no significant effect on histological change, TNF-alpha, IFN-gamma, MCP-1, IL-2, IL-6 and IL-10 expression, CD4(+) T, CD8(+) T, or neutrophil and macrophage counts. Our findings suggest that SH was biocompatible and non-immunogenic. Later, we observed that adhesion not only affected the survival of the graft without mediating rejection, but was closely related to the severity of rejection as manifested by larger and more severe adhesion formation in total-allomismatched and MHC class II allomismatched murine cardiac allografts. Therefore, we inferred that using the murine cervical heterotopic heart transplant model may lead to an exaggerated p value in statistical significance testing which could mislead experimenters in considering that the results are more significant than the fact. To the best of our knowledge, this study is the first demonstration that proves that adhesion was a confounding bias in the murine cervical heterotopic heart transplant model and highlights the possibilities for improvement in future use. PMID- 26550451 TI - Silencing c-Kit expression in human DCs suppresses Th2, Th17 response but enhances Th1 response. AB - Dendritic cells (DCs) are integral to the differentiation of T helper cells into T helper type 1 TH1, TH2 and TH17 subsets. RNA interference (RNAi), which causes the degradation of any RNA in a sequence specific manner, is a posttranscriptional gene silencing mechanism. Targeting the c-Kit in DCs has been used as an approach to enhance antitumor immunity. Here, we shwed that transfection of DCs with siRNA specific for c-Kit gene can significantly knock down c-Kit. When exposed to TNF-alpha, immature DCs transfected with c-Kit siRNA can differentiate into mature DCs without reducing viability or IL-12p70 production. The c-Kit siRNA-treated DCs exhibited an increased allostimulatory capacity in a lymphocyte proliferation assay. Furthermore, c-Kit siRNA transfected DCs enhanced TH1 responses by increasing IFN-gamma and decreasing IL 4 production, and much stronger cytotoxic activity was observed when DCs were co transfected with c-Kit siRNA and an endogenous tumor antigen in vitro. Our findings indicate that silencing the c-Kit gene in DCs with siRNA may offer a potential approach to enhance antitumor immunotherapy. PMID- 26550452 TI - MTRR silencing inhibits growth and cisplatin resistance of ovarian carcinoma via inducing apoptosis and reducing autophagy. AB - Methionine synthase reductase (MTRR) is involved in the DNA synthesis and production of S-adenosylmethionine (SAM) and plays an important role in the carcinogenesis. However, the role of MTRR in the resistance of ovarian cancer (OC) to chemotherapy has yet to be elucidated. In order to investigate the clinical significance of MTRR in OC, MTRR expression was reduced by using the RNA interference technique, and therefore, and the tumor growth and cisplatin resistance were evaluated in vitro and in vivo. Results showed MTRR expression increased orderly from normal tissues, benign ovarian tumor to OC tissue. MTRR over-expression in OC tissue was correlated with pathologic type (P=0.005), grade (P=0.037), FIGO stage (P=0.001), organ metastasis (P=0.009) and platinum resistance (P=0.038). MTRR silencing inhibited cell proliferation, cisplatin resistance and autophagy, and induced apoptosis of OC cells. In addition, MTRR silencing also affected the caspase expression as well as mTOR signaling pathway. Further, the tumor volume in MTRR-suppressed SKOV3/DDP mice treated with cisplatin significantly decreased when compared with controls (P<0.05). In summary, MTRR expression, which is increased in human OC, is related to the differentiation and cisplatin resistance of OC cells. MTRR silencing inhibits cell growth and cisplatin resistance by regulating caspase expression and mTOR signaling pathway in OC cells. It is suggested that MTRR may be a potential target for the therapy of OC. PMID- 26550453 TI - PX-12 inhibits the growth of hepatocelluar carcinoma by inducing S-phase arrest, ROS-dependent apoptosis and enhances 5-FU cytotoxicity. AB - BACKGROUND: 1-methylpropyl 2-imidazolyl disulfide (PX-12), a thioredoxin 1 (Trx1) inhibitor, has been investigated in a number of ancers, but its effectiveness in the treatment of hepatocellular carcinoma (HCC) has not been reported. PX-12 has generated considerable interest in its use in a variety of solid tumors, yet most studies have confined their interests to using PX-12 as a single agent. The aim of this study is to investigate whether PX-12 inhibits cell growth and has a synergistic anti-tumor effect in combination with 5-fluorouracil (5-FU) in HCC. METHODS: Cells were treated with different concentrations of PX-12 and 5-FU. Cell viability assays, colony formation assay, cell cycle assay, reactive oxygen species (ROS) assay, apoptosis analysis, western blot assay, immunohistochemistry and xenograft tumorigenicity assay were performed. RESULTS: Treatment with PX-12 inhibited cell growth, induced S-phase arrest, and increased ROS levels. PX-12 induced apoptosis and inhibition of colony formation were associated with the generation of ROS, and inhibition of ROS attenuated PX-12-induced apoptosis and inhibition of colony formation. Treatment with PX-12 increased the expression of bax and reduced the expression of bcl-2, indicating that PX-12-mediated apoptosis is mitochondria-dependent. PX-12 also exerted a synergistic effect with 5-FU tosignificantly suppress tumorigenicity both in vitro and in vivo. Inhibition of ROS accumulation reduced the synergistic effect of PX-12 and 5-FU. CONCLUSIONS: PX-12 has anti-tumor activity and a synergistic effect in combination with 5-FU in HCC. Treatment with PX-12 alone or in combination with 5-FU may have clinical use in the treatment of HCC and other cancers. PMID- 26550454 TI - NF-kappaB protects human neuroblastoma cells from nitric oxide-induced apoptosis through upregulating biglycan. AB - Excessive nitric oxide (NO) produced in inflammation may result in oxidative stress, which is closely related to the neurodegenerative diseases and brain damage. Massive NO production can enhance NF-kappaB activity in various neural cells, but the function of this activation by NO and the target genes transactivated by NF-kappaB are still largely unknown. In the present study, our results showed sodium nitropruside (SNP), a NO donor, triggered apoptotic cell death and NF-kappaB activation in human neuroblastoma SH-EP1 cells, and inhibition of NF-kappaB activation by its super endogenous inhibitor, I kappaBalphaM, sensitized SH-EP1 cells to NO-induced apoptosis. Conversely, NF kappaB activation induced by insulin-like growth factor (IGF)-1 antagonizes NO induced apoptotic cell death in SH-EP1 cells. In addition, cDNA microarray analysis showed biglycan, an extracellular glycoprotein, was up-regulated by NF kappaB, and recombinant biglycan protein conferred a protective effect on NF kappaB mediated NO-induced apoptotic cell death in SH-EP1 cells. These findings suggest biglycan may serve as a potential target in preventing NO-induced neurodegenerative diseases. PMID- 26550455 TI - Low molecular weight fucoidan ameliorates diabetic nephropathy via inhibiting epithelial-mesenchymal transition and fibrotic processes. AB - Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and may lead to end-stage renal disease (ESRD) and chronic renal failure. The aim of this study was to determine whether low-molecular-weight fucoidan (LMWF) can reduce harmful transforming growth factor-beta (TGF-beta) mediated renal fibrosis in DN using in vitro and in vivo experimental models. The experimental results showed that LMWF significantly reversed TGF-beta1-induced epithelial-mesenchymal transition and dose-dependently inhibited accumulation of extracellular matrix proteins, including connective tissue growth factor and fibronectin. It was found that LMWF significantly reduced blood urea nitrogen and blood creatinine in both type 1 and type 2 diabetic rat models. H&E, PAS and Masson's trichrome staining of kidney tissue showed LMWF significantly reduced renal interstitial fibrosis. Treatment with LMWF significantly increased E cadherin expression and reduced alpha-SMA, CTGF and fibronectin expression in both type 1 and type 2 diabetic models. LMWF also decreased the phosphorylation of Akt, ERK1/2, p38 and Smad3 in vitro and in vivo. These data suggest that LMWF may protect kidney from dysfunction and fibrogenesis by inhibiting TGF-beta pathway and have the potential benefit to slow down the progression of DN. PMID- 26550456 TI - miR-128 modulates hepatocellular carcinoma by inhibition of ITGA2 and ITGA5 expression. AB - Dysregulation of miRNAs is a common feature in human cancers, but this phenomenon has not been studied extensively in hepatocellular carcinoma (HCC). miR-128 has been found to be downregulated in cancer. However its role in HCC remains unclear. miR-128 was underexpressed in HCC tissues and cell lines compared with their normal controls. Additionally, ITGA2 and ITGA5 were predicted as the target genes of miR-128. ITGA2 and ITGA5 were inversely correlated with the expression of miR-128 in HCC cells. Importantly, we demonstrate that the overexpression of miR-128 significantly inhibits HCC cell metastasis and stem-cell like properties via ITGA2 and ITGA5. Our results suggest the existence of a novel miR-128-ITGA pathway and indicate that miR-128 acts as a tumor suppressor during hepatocellular carcinogenesis. These results may provide a promising alternative strategy for the therapeutic treatment of HCC. PMID- 26550457 TI - The altered autophagy mediated by TFEB in animal and cell models of amyotrophic lateral sclerosis. AB - Autophagy is an intracellular degradation process that clears away aggregated proteins or aged and damaged organelles. Abnormalities in autophagy result in defects in clearance of these misfolded and aggregate proteins, which have been associated with neurodegenerative disorders. A key neuropathological hallmark of amyotrophic lateral sclerosis (ALS) that contributes to the progressive loss of motor neurons is abnormal protein aggregation of mutant Cu/Zn superoxide dismutase1 (SOD1). TFEB is a recently described gene that regulates autophagy. Several studies have reported that autophagy is altered in ALS, but little is known about the role and mechanisms of TFEB-mediated autophagy during the progression of ALS. In this study, altered expression of TFEB and Beclin-1 were detected in the spinal cords of ALS transgenic mice at different stages and in an NSC-34 cell model with the SOD1-G93A mutation using RT-PCR, western blot, and immunohistochemistry. The majority of cells positive for TFEB and Beclin-1 are beta-tubulin III-labeled neurons, especially in the anterior horn of the gray matter. Overexpression of TFEB in NSC-34 cells with the SOD1-G93A mutation increased the mRNA and protein levels of Beclin-1, accompanied by increased levels of LC3-II protein. MTS assay revealed that TFEB overexpression increased proliferation and survival of NSC-34 cells with the SOD1-G93A mutation. Our findings suggest that TFEB promotes autophagy by enhancing the expression of Beclin-1. The altered autophagy mediated by TFEB is a key element in the pathogenesis of ALS, making TFEB a very promising target for the development of novel drugs and new gene therapeutics for ALS. PMID- 26550458 TI - The effect of synthetic alpha-tricalcium phosphate on osteogenic differentiation of rat bone mesenchymal stem cells. AB - The reconstruction of large bone defects has been the focus in bone tissue engineering research. By acting as synthetic frameworks for cell growth and tissue formation, biomaterials can play a critical role in bone tissue engineering. Among various biomaterials, calcium phosphate based materials include hydroxyapatite (HA), alpha-tricalcium phosphate (alpha-TCP), and beta tricalcium phosphate (beta-TCP) are widely used as scaffold materials in bone tissue engineering. However, little is known about the effect of alpha-TCP alone on the osteogenic differentiation of the BMSCs. To this end, we synthesized alpha TCP using a novel co-precipitation method. The synthetic alpha-TCP was then incubated with rat BMSCs under osteogenic inductive medium culture conditions, followed by the analysis of the mRNA levels of various osteogenesis-related genes, including ALP, Rux2, COL-I, and SP7, using a quantitative RT-PCR method. Following incubation of BMSCs with 20 MUg/ml alpha-TCP, cells reached confluency after 7 days. Additionally, the MTT analysis showed that alpha-TCP at concentration of 10-20 MUg/ml had good biocompatibility with BMSCs, showing no significant inhibition of rat BMSCs proliferation. Furthermore, the synthetic alpha-TCP (20 MUg/ml), when incubated with rat BMSCs in the osteogenic culture medium, increased the mRNA levels of various osteogenesis-related genes, including ALP, Rux2, COL-I, and SP7. Finally, treatment of synthetic alpha-TCP (20 MUg/ml) potentiated calcium nodule formations after incubation with rat BMSCs in osteogenic culture medium for 21 days, as compared with non-treated control. Taken together, the results in the present study suggested that alpha-TCP alone likely promotes rat BMSCs osteogenic differentiation through up-regulating ALP, Col-I, Runx2, and SP7 gene expression. PMID- 26550459 TI - Eplerenone attenuates cardiac dysfunction and oxidative stress in beta-receptor stimulated myocardial infarcted rats. AB - Eplerenone is a competitive antagonist of the aldosterone receptor with an additional PI3K-Akt activity. The existing cram has been intended to explore, whether eplerenone treatment attenuates the expansion of myocardial infarction in isoproterenol treated rats by restoring hemodynamic, biochemical, and histopathological changes. Isoproterenol induced cardiotoxicity was evidenced by marked ST elevation, decrease in systolic, diastolic, mean arterial pressures. Maximal positive rate of developed left ventricular pressure (+LVdP/dt max, a indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt max, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load) were also shown. In addition, a significant reduction in activities of myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione level along with increase in malondialdehyde content were observed. Oral pre-treatment with eplerenone (50, 100 and 150 mg/kg) daily for a period of 14 days, constructively modulated the studied parameters in isoproterenol-induced myocardial injury. The protective role of eplerenone on isoproterenolinduced myocardial damage was further confirmed by histopathological examinations. Eplerenone at doses of 100 mg/kg and 150 mg/kg produced more pronounced protective effects than 50 mg/kg body weight. Together, our study provides evidence for protective effects of eplerenone on myocardium in experimentally induced myocardial infarction. PMID- 26550460 TI - Upregulation of cyclooxygenase-2 is associated with activation of the alternative nuclear factor kappa B signaling pathway in colonic adenocarcinoma. AB - Cyclooxygenase-2 expression by malignant tumors, including colonic adenocarcinoma, is associated with increased tumor aggression and poor prognosis. Nuclear factor kappa B is a key regulator of cyclooxygenase-2 and is regulated by two pathways, the 'canonical' and the 'alternative' pathway. The alternative pathway is triggered by members of the tumor necrosis factor cytokine family, including RelB and p52. This present study was undertaken to evaluate cyclooxygenase-2 and the alternative nuclear factor-kappa B signaling pathway in colonic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue samples diagnosed with colonic adenocarcinoma and a human colonic adenocarcinoma cell line, LS174, were studied. The expression of cyclooxygenase-2, RelB and p52 were determined using immunohistochemistry, immunofluorescence, and Western blots. Quantitative analysis of mRNA by real-time reverse transcriptase polymerase chain reaction and chromatin immunoprecipitation were performed on the tissue and cell samples. To investigate nuclear factor kappa B gene regulation of the cyclooxygenase-2 gene, dual luciferase assays were performed, and LS174 cells were transfected with RelB or p100/p52 short interfering RNA. Upregulation of cyclooxygenase-2 was associated with activation of the alternative nuclear factor kappa B signaling pathway components RelB, and p52, in colonic adenocarcinoma cells in tissues and the cell line, LS174. Chromatin immunoprecipitation assay determined that cyclooxygenase-2 gene was associated with both RelB and p52. A luciferase reporter assay showed that the nuclear factor kappa B enhancer of cyclooxygenase-2 was sufficient to regulate the transcriptional activity of a heterologous promoter in LS174 cells. RNA interference-mediated knockdown of RelB or p52 resulted in significant inhibition of cyclooxygenase-2 at both mRNA and protein levels in LS174 cells. These findings support a potential role for inhibition of components of the alternative nuclear factor kappa B signaling pathway, RelB-p52-cyclooxygenase-2, as a possible therapeutic target in the treatment of adenocarcinoma of the colon. Further studies on the role of this pathway in this and other malignancies are recommended. PMID- 26550461 TI - High expression of WISP-1 correlates with poor prognosis in pancreatic ductal adenocarcinoma. AB - WNT1 inducible signaling pathway protein 1 (WISP-1) is a member of the CCN family of growth factors and reported to possess an important role in tumorigenesis by triggering downstream events via integrin signaling. However, the exact role of WISP-1 in cancer remains unclear. In this study, we examined the expression pattern of WISP-1 at both mRNA and protein levels and evaluated the prognostic value of WISP-1 in pancreatic ductal adenocarcinoma (PDA). Expression of WISP-1 at mRNA level was upregulated in 17/24 tumor tissues compared to the matched adjacent non-tumor tissues and the result was confirmed by western blotting at protein level. Immunohistochemical staining of 194 pairs of PDA specimens suggested that high expression of WISP-1 is strongly correlated with clinical stage (P=0.003), T classification (P=0.008) and liver metastasis (P=0.012). Consistently, Kaplan-Meier survival curves indicated that patients with high expression of WISP-1 had a shorter survival time independent of clinical stage and lymphatic metastasis status. Moreover, univariate and multivariate analysis confirmed WISP-1 expression, age, classification and liver metastasis as independent prognostic factors for overall survival of PDA patients. Taken together, these results suggest that WISP-1 may serve as a potential prognostic biomarker for PDA. PMID- 26550462 TI - Identification of a novel role of RING finger protein 11 promoting the metastasis of murine melanoma cells. AB - Melanoma is the leading cause of skin cancer death owing to its highly metastatic nature and resistance to chemotherapy. It may account for 80% of the deaths relating to skin cancers. Once it progressed to metastatic stage, no current effective treatment is available for melanoma. Therefore, in-depth understanding of the mechanism underlying the metastatic process is imperative and would be of great help for improving the treatment of melanoma. Here, wedemonstrate that RING finger protein 11 (RNF11) disruption by insertional mutagenesis impairs the metastatic potential of murine melanoma B16F10 cells. The requirement of RNF11 in the migration of melanoma cells is further confirmed by gene knockdown and overexpression experiments in vitro. Together, our findings suggest a novel role of RNF11 in promoting the metastasis of melanoma cells which may potentially be useful for the treatment of melanoma by developing a new intervention target. PMID- 26550463 TI - The human subject: an integrative animal model for 21(st) century heart failure research. AB - Heart failure remains a leading cause of death and it is a major cause of morbidity and mortality affecting tens of millions of people worldwide. Despite decades of extensive research conducted at enormous expense, only a handful of interventions have significantly impacted survival in heart failure. Even the most widely prescribed treatments act primarily to slow disease progression, do not provide sustained survival advantage, and have adverse side effects. Since mortality remains about 50% within five years of diagnosis, the need to increase our understanding of heart failure disease mechanisms and development of preventive and reparative therapies remains critical. Currently, the vast majority of basic science heart failure research is conducted using animal models ranging from fruit flies to primates; however, insights gleaned from decades of animal-based research efforts have not been proportional to research success in terms of deciphering human heart failure and developing effective therapeutics for human patients. Here we discuss the reasons for this translational discrepancy which can be equally attributed to the use of erroneous animal models and the lack of widespread use of human-based research methodologies and address why and how we must position our own species at center stage as the quintessential animal model for 21(st) century heart failure research. If the ultimate goal of the scientific community is to tackle the epidemic status of heart failure, the best way to achieve that goal is through prioritizing human based, human-relevant research. PMID- 26550464 TI - Protective effect of histamine microinjected into the cerebellar fastigial nucleus on stress-induced gastric mucosal damage in rats. AB - AIMS: We investigated the effffects and the possible mechanism of microinjection of histamine into cerebellar fastigial nucleus (FN) on stress-induced gastric mucosal damage (SGMD) in rats. The effect of microinjection of histamine into FN on SGMD was observed. METHODS: The model of SGMD was established by restraint and water (21 +/- 1 degrees C)-immersion (RWI) for 3 h in rats. The gastric mucosal damage index indicated the severity of SGMD. Western blotting was performed to assess gastric mucosal cell apoptosis and proliferation. RESULTS: We observed that histamine microinjection into the FN markedly attenuated SGMD in a dose dependent manner, and was prevented by pre-treatment with the ranitidine (a selective histamine H2 receptor antagonist) into the FN. The effect of histamine was abolished by pre-treatment with 3-MPA (a glutamic acid decarboxylase antagonist) into the FN. There was a decrease in the discharge frequency of greater splanchnic nerve, and an increase in gastric mucosal blood flow after histamine injection into the FN. Additionally, anti-apoptotic and anti-oxidative factors of gastric mucosa might be involved in this process. CONCLUSION: The exogenous histamine in FN participates in the regulation of SGMD, and our results may help to provide new ideas on the treatment of gastroenterological diseases. PMID- 26550465 TI - Biological roles of human bone morphogenetic protein 9 in the bone microenvironment of human breast cancer MDA-MB-231 cells. AB - Bone marrow stroma plays a critical role in the bone metastasis of breast cancer. Bone marrow-derived mesenchymal stem cells (BMSC) are critical to facilitate cancer progression. Human bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor and one of bone-stored growth factors involved in both promotion and inhibition of different cancers. However, it is unclear whether BMP9 correlates with the bone metastasis of breast cancer. This study was to evaluate the role of BMP9 in the interaction between BMSC and breast cancer cells (BCC). To determine whether BMP9 is able to block the tumor promoting effect of BMSC, an in vitro model was developed using breast cancer MDA-MB-231 cells co cultured with bone marrow-derived mesenchymal stem cells HS-5 with-BMP9 overexpression. The expressions of metastasis-related genes were detected to identify important factors mediating the role of BMP9 in breast cancer cells. Results showed BMP9 could inhibit invasion and promote apoptosis of MDA-MB-231 cells. The expressions of interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP 2) and monocyte chemoattratctant protein-1 (MCP-1) decreased in the MDA-MB-231 cells of BMP9 over-expression group, and the expressions of epithelial mesenchymal transition (EMT)-related molecules was also reduced. On the other hand, the expression of stromal cell derived factor-1 (SDF-1) decreased in HS-5 cells of BMP9 over-expression group. Taken together, BMP9 is able to inhibit the migration and promote the apoptosis of breast cancer by regulating the interaction between MDA-MB-231 cells and HS-5 cells in which SDF-1/CXCR4-PI3K pathway and EMT are involved. PMID- 26550466 TI - The FDA's Final Rule on Expedited Safety Reporting: Statistical Considerations. AB - In March 2011, a Final Rule for expedited reporting of serious adverse events took effect in the United States for studies conducted under an Investigational New Drug (IND) application. In December 2012, the U.S. Food and Drug Administration (FDA) promulgated a final Guidance describing the operationalization of this Final Rule. The Rule and Guidance clarified that a clinical trial sponsor should have evidence suggesting causality before defining an unexpected serious adverse event as a suspected adverse reaction that would require expedited reporting to the FDA. The Rule's emphasis on the need for evidence suggestive of a causal relation should lead to fewer events being reported but, among those reported, a higher percentage actually being caused by the product being tested. This article reviews the practices that were common before the Final Rule was issued and the approach the New Rule specifies. It then discusses methods for operationalizing the Final Rule with particular focus on relevant statistical considerations. It concludes with a set of recommendations addressed to Sponsors and to the FDA in implementing the Final Rule. PMID- 26550468 TI - Letters to the Editor. PMID- 26550467 TI - Early modern human dispersal from Africa: genomic evidence for multiple waves of migration. AB - BACKGROUND: Anthropological and genetic data agree in indicating the African continent as the main place of origin for anatomically modern humans. However, it is unclear whether early modern humans left Africa through a single, major process, dispersing simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Oceania, and later through a northern route crossing the Levant. RESULTS: Here, we show that accurate genomic estimates of the divergence times between European and African populations are more recent than those between Australo-Melanesia and Africa and incompatible with the effects of a single dispersal. This difference cannot possibly be accounted for by the effects of either hybridization with archaic human forms in Australo-Melanesia or back migration from Europe into Africa. Furthermore, in several populations of Asia we found evidence for relatively recent genetic admixture events, which could have obscured the signatures of the earliest processes. CONCLUSIONS: We conclude that the hypothesis of a single major human dispersal from Africa appears hardly compatible with the observed historical and geographical patterns of genome diversity and that Australo Melanesian populations seem still to retain a genomic signature of a more ancient divergence from Africa. PMID- 26535109 TI - Detecting miRNA Mentions and Relations in Biomedical Literature. AB - Introduction: MicroRNAs (miRNAs) have demonstrated their potential as post transcriptional gene expression regulators, participating in a wide spectrum of regulatory events such as apoptosis, differentiation, and stress response. Apart from the role of miRNAs in normal physiology, their dysregulation is implicated in a vast array of diseases. Dissection of miRNA-related associations are valuable for contemplating their mechanism in diseases, leading to the discovery of novel miRNAs for disease prognosis, diagnosis, and therapy. Motivation: Apart from databases and prediction tools, miRNA-related information is largely available as unstructured text. Manual retrieval of these associations can be labor-intensive due to steadily growing number of publications. Additionally, most of the published miRNA entity recognition methods are keyword based, further subjected to manual inspection for retrieval of relations. Despite the fact that several databases host miRNA-associations derived from text, lower sensitivity and lack of published details for miRNA entity recognition and associated relations identification has motivated the need for developing comprehensive methods that are freely available for the scientific community. Additionally, the lack of a standard corpus for miRNA-relations has caused difficulty in evaluating the available systems. We propose methods to automatically extract mentions of miRNAs, species, genes/proteins, disease, and relations from scientific literature. Our generated corpora, along with dictionaries, and miRNA regular expression are freely available for academic purposes. To our knowledge, these resources are the most comprehensive developed so far. Results: The identification of specific miRNA mentions reaches a recall of 0.94 and precision of 0.93. Extraction of miRNA-disease and miRNA-gene relations lead to an F 1 score of up to 0.76. A comparison of the information extracted by our approach to the databases miR2Disease and miRSel for the extraction of Alzheimer's disease related relations shows the capability of our proposed methods in identifying correct relations with improved sensitivity. The published resources and described methods can help the researchers for maximal retrieval of miRNA relations and generation of miRNA-regulatory networks. Availability: The training and test corpora, annotation guidelines, developed dictionaries, and supplementary files are available at http://www.scai.fraunhofer.de/mirna corpora.html. PMID- 26535109 TI - Detecting miRNA Mentions and Relations in Biomedical Literature. AB - INTRODUCTION: MicroRNAs (miRNAs) have demonstrated their potential as post transcriptional gene expression regulators, participating in a wide spectrum of regulatory events such as apoptosis, differentiation, and stress response. Apart from the role of miRNAs in normal physiology, their dysregulation is implicated in a vast array of diseases. Dissection of miRNA-related associations are valuable for contemplating their mechanism in diseases, leading to the discovery of novel miRNAs for disease prognosis, diagnosis, and therapy. MOTIVATION: Apart from databases and prediction tools, miRNA-related information is largely available as unstructured text. Manual retrieval of these associations can be labor-intensive due to steadily growing number of publications. Additionally, most of the published miRNA entity recognition methods are keyword based, further subjected to manual inspection for retrieval of relations. Despite the fact that several databases host miRNA-associations derived from text, lower sensitivity and lack of published details for miRNA entity recognition and associated relations identification has motivated the need for developing comprehensive methods that are freely available for the scientific community. Additionally, the lack of a standard corpus for miRNA-relations has caused difficulty in evaluating the available systems. We propose methods to automatically extract mentions of miRNAs, species, genes/proteins, disease, and relations from scientific literature. Our generated corpora, along with dictionaries, and miRNA regular expression are freely available for academic purposes. To our knowledge, these resources are the most comprehensive developed so far. RESULTS: The identification of specific miRNA mentions reaches a recall of 0.94 and precision of 0.93. Extraction of miRNA-disease and miRNA-gene relations lead to an F 1 score of up to 0.76. A comparison of the information extracted by our approach to the databases miR2Disease and miRSel for the extraction of Alzheimer's disease related relations shows the capability of our proposed methods in identifying correct relations with improved sensitivity. The published resources and described methods can help the researchers for maximal retrieval of miRNA relations and generation of miRNA-regulatory networks. AVAILABILITY: The training and test corpora, annotation guidelines, developed dictionaries, and supplementary files are available at http://www.scai.fraunhofer.de/mirna corpora.html. PMID- 26535110 TI - Effect of environmental and cultural conditions on medium pH and explant growth performance of Douglas-fir ( Pseudotsuga menziesii) shoot cultures. AB - The medium pH level of plant tissue cultures has been shown to be essential to many aspects of explant development and growth. Sensitivity or tolerance of medium pH change in vitro varies according to specific requirements of individual species. The objectives of this study are to 1) determine medium pH change over time in storage conditions and with presence of explants, 2) evaluate the effects of medium pH change on explant growth performance and 3) assess the effects of adding a pH stabilizer, 2-(N-morpholino)ethanesulfonic acid (MES) that is commonly used in Douglas-fir micropropagation medium. Vegetative buds were collected in the spring before breaking dormancy from juvenile and mature donor trees for conducting these evaluations. Medium, with or without MES, was pre adjusted to five pH levels before adding MES, agar and autoclaving. Medium pH changes and explant growth parameters were measured at eight different incubation times. Overall, MES provided a more stable medium pH, relative to starting pH values, under both light and dark storage conditions as well as with presence of explants. A general trend of decreasing medium pH over time was found comparing explants from juvenile and mature donor genotypes. Explant height and weight growth increased over time, but differ among explants from juvenile and mature donor genotypes. Our findings suggest that a 21-day subculture practice may best sustain medium freshness, medium pH level and desirable explant growth. PMID- 26539290 TI - Rampant software errors may undermine scientific results. AB - The opportunities for both subtle and profound errors in software and data management are boundless, yet they remain surprisingly underappreciated. Here I estimate that any reported scientific result could very well be wrong if data have passed through a computer, and that these errors may remain largely undetected. It is therefore necessary to greatly expand our efforts to validate scientific software and computed results. PMID- 26550474 TI - In vitro antimicrobial activity of a novel compound, Mul-1867, against clinically important bacteria. AB - BACKGROUND: The antimicrobial activity of Mul-1867, a novel synthetic compound, was tested against 18 bacterial strains, including clinical isolates and reference strains from culture collections. METHODS: The minimal inhibitory concentration (MICs) and minimal bactericidal concentration (MBCs) were determined by using the broth macrodilution method. The kinetics of the inhibitory effects of Mul-1867 against biofilm-growing microorganisms was assessed at time-kill test in vitro against 48-h-old biofilms of Staphylococcus aureus and Escherichia coli. Transmission electron microscopy analyses was conducted to examine cell disruption. RESULTS: A comparative assessment of the antimicrobial activities of Mul-1867 and chlorhexidine digluconate (CHG), used as a control antimicrobial, indicated that Mul-1867 was significantly more effective as a disinfectant than CHG. Mul-1867 showed potent antimicrobial activities against all the tested bacteria (MIC: 0.03-0.5 MUg/mL). Furthermore, MBC/MIC ratio of Mul-1867 for all tested strains was less than or equal to 4. Time-kill studies showed that treatment with Mul-1867 (0.05-2 %) reduced bacterial numbers by 2.8-4.8 log10 colony forming units (CFU)/mL within 15-60 s. Bactericidal activity of Mul-1867 was confirmed by morphological changes revealed by TEM suggested that the killing of bacteria was the result of membrane disruption. CONCLUSION: Overall, these data indicated that Mul-1867 may be a promising antimicrobial for the treatment and prevention of human infections. PMID- 26550473 TI - Full-length single-cell RNA-seq applied to a viral human cancer: applications to HPV expression and splicing analysis in HeLa S3 cells. AB - BACKGROUND: Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas. Recent single-cell RNA seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied. HeLa is a well characterized HPV+ cervical cancer cell line. RESULT: We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip. Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing. Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions. Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level. By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins. CONCLUSION: Our results reveal the heterogeneity of a virus-infected cell line. It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers. PMID- 26550475 TI - Crystal structures of CaSiO3 polymorphs control growth and osteogenic differentiation of human mesenchymal stem cells on bioceramic surfaces. AB - The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure-reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, beta-CaSiO3) and wollastonite (wol, alpha CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were more osteoinductive for the former. Thus, we showed that crystal structure is a fundamental parameter to be considered in the intelligent design of pro-osteogenic, partially resorbable bioceramics. PMID- 26550476 TI - Association of Beck Depression Inventory score and Temperament and Character Inventory-125 in patients with eating disorders and severe malnutrition. AB - The authors investigated the association between personality and physical/mental status in malnourished patients with eating disorders. A total of 45 patients with anorexia nervosa, avoidant/restrictive food intake disorder, and other specified feeding or eating disorders were included and compared with 39 healthy controls. Personality characteristics and severity of depression were assessed using the Temperament and Character Inventory-125 and Beck's Depression Inventory. Depression correlated with harm avoidance and self-directedness in both cases and controls. Body mass index did not correlate with personality in either group. These findings should be verified by longitudinal studies with higher weight/weight recovered patients. PMID- 26550477 TI - Evaluation of an online training program in eating disorders for health professionals in Australia. AB - BACKGROUND: Early detection and treatment of eating disorders is instrumental in positive health outcomes for this serious public health concern. As such, workforce development in screening, diagnosis and early treatment of eating disorders is needed. Research has demonstrated both high rates of failure to accurately diagnose and treat cases early and low levels of perceived access to training in eating disorders by health professionals-representing an urgent need for clinician training in this area. However, significant barriers to the access of evidence-based training programs exist, including availability, cost and time, particularly when large geographic distances are involved. Online learning presents a solution to workforce challenges, as it can be delivered anywhere, at a fraction of the cost of traditional training, timing is user controlled, and a growing body of research is demonstrating it as effective as face-to-face training. The Centre for Eating and Dieting Disorders in Australia has developed an Online Training Program In Eating Disorders, to educate health professionals in the nature, identification, assessment and management of eating disorders. The aim of the current study was to evaluate the ability of this online learning course to improve clinician levels of knowledge, skill and confidence to treat eating disorders. As well as its effect on stigmatised beliefs about eating disorders known to effect treatment delivery. METHODS: One-hundred-eighty-seven health professionals participated in the program. A pre training questionnaire and a post training evaluation examined participants' levels of knowledge, skill and confidence to treat eating disorders, as well attitudes and beliefs about people with eating disorders. RESULTS: Significant improvements in knowledge, skill, and confidence to treat eating disorders was found between pre and post program assessment in health professionals who completed the course, along with a significant decrease in stigmatised beliefs about eating disorders. DISCUSSION: The results of this study demonstrated that the online training program was an effective tool in increasing health professionals' level of knowledge, skill and confidence to treat people with eating disorders. The results also demonstrated that online training reduced health professionals' personal bias towards people with eating disorders. Limitations of this study include the use of self-report measures rather than observation of the health professional in clinical practice. As a result, it is not possible to make determinations regarding the translation of these results to clinical settings. CONCLUSIONS: The findings of this study suggest that online training programs may present an innovative solution to the considerable workforce development challenges faced by clinicians needing training in eating disorders. PMID- 26550478 TI - Three cases of appendicitis with anorexia nervosa under inpatient care. AB - BACKGROUND: Little is known about the occurrence of appendicitis during the re nourishment period in anorexia nervosa (AN). We report three cases of appendicitis in patients with AN that occurred after hospitalization for treatment of AN. CASE PRESENTATION: Case 1 is a 34-year-old female, case 2 is a 17-year-old female and case 3 is a 38-year-old female. Constipation was observed in all three cases. Careful management of defecation might be essential to prevent appendicitis among AN patients during the re-nourishment period under inpatient care. In addition, mild and diffuse symptoms were observed in all three cases. Therefore, diagnosis proved to be difficult to make and abdominal computed tomography was particularly helpful in all cases. As the symptoms were diffuse, the condition of appendicitis turned out to be more severe and complicated in one case. Additionally, the incidence of appendicitis in AN in the current study might be higher than that in the normal population. CONCLUSIONS: These findings suggest that appendicitis should be considered as one of the potentially important complications in the therapy for AN. PMID- 26550479 TI - Sonoporation efficacy on SiHa cells in vitro at raised bath temperatures experimental validation of a prototype sonoporation device. AB - BACKGROUND: A device was devised which aimed to reduce the time and expertise required to perform sonoporation on adherent cell cultures. This prototype device was used to examine the superficial effect of bath temperature on sonoporation efficacy. METHODS: The prototype device consisted of six ultrasound transducers affixed beneath an Opticell stage. Six transducers with nominal diameters of 20 mm were constructed and the acoustic field of each was characterized using hydrophone scanning. A near field treatment plane was chosen for each transducer to minimize field heterogeneity in the near field. Cervical cancer-derived SiHa cells were exposed to nine different treatments in the presence of plasmid DNA expressing green fluorescent protein (GFP). Ultrasound treatment with Definity ultrasound contrast agent (US+UCA) present, ultrasound treatment without contrast agent present (US), and a sham ultrasound treatment in the presence of ultrasound contrast agent (CA) were each performed at bath temperatures of 37, 39.5, and 42 degrees C. Each treatment was performed in biological triplicate. GFP expression and PARP expression following treatment were measured using fluorescent microscopy and digital image processing. Cell detachment was measured using phase contrast microscopy before and after treatment. RESULTS: Mean (+/- s.d.) transfection rates for the US+UCA treatment were 5.4(+/-0.92), 5.8(+/-1.3), and 5.3(+/-1.1) % at 37, 39.5, and 42 degrees C, respectively. GFP expression and cell detachment were both significantly affected by the presence of ultrasound contrast agent (p < 0.001, p < 0.001). Neither GFP expression, PARP expression, or detachment differed significantly between bath temperatures. CONCLUSIONS: Bath temperature did not impact the efficacy of sonoporation treatment on SiHa cells in vitro. The prototype device was found to be suitable for performing sonoporation on adherent cell cultures and will reduce the time and expertise required for conducting sonoporation experiments on adherent cell cultures in the future. PMID- 26550480 TI - Target antigens for Hs-14 monoclonal antibody and their various expression in normozoospermic and asthenozoospermic men. AB - BACKGROUND: Poor semen quality is one of the main causes of infertility. We have generated a set of monoclonal antibodies to human sperm and used them to investigate sperm quality. Some of these antibodies found differences in the expression of proteins between normal sperm and pathological sperm displaying severe defects. One of them was the Hs-14 antibody. The aim of this paper was to determine the target protein of the Hs-14 monoclonal antibody and to investigate the expression of the Hs-14-reacting protein on the sperm of asthenozoospermic men with sperm motility defect and of healthy normozoospermic men. METHODS: Indirect immunofluorescence, one-dimensional and two-dimensional polyacrylamide gel electrophoresis, immunoblotting and mass spectrometry. RESULTS: The Hs-14 antibody binds fibronectin, beta-tubulin and valosin-containing protein - new name for this protein is transitional endoplasmic reticulum ATPase (TERA). Since the Hs-14 reaction with TERA remained the strongest at the highest antibody dilution, and Hs-14 consistently labelled the same spot or band as the monospecific anti-TERA antibody on immunoblots, we assume that TERA is an Hs-14 specific protein. Binding of fibronectin and beta-tubulin might represent nonspecific cross-reactivity or Hs-14 reaction with similar epitopes of these proteins. A significant difference (P < 0.001) in immunofluorescence staining with Hs-14 was found between the normozoospermic and asthenozoospermic men. CONCLUSION: The Hs-14 antibody enables discrimination between sterile or subfertile asthenozoospermic and fertile normozoospermic men. Decreased levels of TERA in men can be used as a biomarker of reduced fertility. PMID- 26550481 TI - Diffuse interstitial and multiple cavitary lung lesions due to Talaromyces marneffei infection in a non-HIV patient. AB - A 57-year-old man presented with unproductive cough and dyspnea for 6 months in Fujian Province, China. His misuse of a large amount of steroids (accumulated dose equivalent to 3530 mg prednisolone) resulted in Talaromyces marneffei infection. Chest computed tomographic scan revealed diffuse interstitial and multiple cavitary lung lesions. Treatment with amphotericin B combined with itraconazole resulted in total recovery, with marked regression of lung lesions. PMID- 26550482 TI - Overlooked Holmes' clinical signs: reevaluation by recent physiological findings. AB - Holmes proposed not only the term ataxia, but also opposite clinical signs related to muscle recruitment, which have escaped clinical attention; (1) asthenia, representing delay in initiating muscle contraction and slowness in attaining exertion of full power, and (2) adventitiousness, representing adventitious movements. Recent physiological studies have shown that cerebellar outputs are modified by release or facilitation of Purkinje cell-mediated inhibition on dentate neurons. We believe that asthenia and adventitiousness, which correlate with deficits in the control of disinhibition and inhibition, respectively, deserve more attention in clinical examination. PMID- 26550483 TI - Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance. AB - BACKGROUND: Dimethyl fumarate (DMF), a disease-modifying therapy for multiple sclerosis (MS), causes lymphopenia in a fraction of patients. The clinical significance of this is unknown. Several cases of progressive multifocal leukoencephalopathy in lymphopenic fumarate-treated patients have raised concerns about drug safety. Since lymphocytes contribute to MS pathology, lymphopenia may also be a biomarker for response to the drug. OBJECTIVE: The objective of this manuscript is to evaluate risk factors for DMF-induced lymphopenia and drug failure in a real-world population of MS patients. METHODS: We conducted a retrospective cohort study of 221 patients prescribed DMF at a single academic medical center between March 2013 and February 2015. RESULTS: Grade 2-3 lymphopenia developed in 17% of the total cohort and did not resolve during DMF treatment. Older age (>55), lower baseline absolute lymphocyte count and recent natalizumab exposure increased the risk of developing moderate to severe lymphopenia while on DMF. Lymphopenia was not predictive of good clinical response or of breakthrough MS activity on DMF. CONCLUSIONS: Lymphopenia develops in a significant minority of DMF-treated patients, and if grade 2 or worse, is unlikely to resolve while on the drug. Increased vigilance in lymphocyte monitoring and infection awareness is particularly warranted in older patients and those switching from natalizumab. PMID- 26550484 TI - Relationship between obesity and coronary heart disease among urban Bangladeshi men and women. AB - The aim of the study was to examine the association of different measures of obesity (body mass index or BMI, waist circumference or WC, waist to hip ratio or WHR and waist height ratio or WHtR) with coronary heart disease (CHD) in a Bangladeshi population. The study included 189 hospitalized CHD cases (133 men and 52 women) and 201 controls (137 men and 68 women). Logistic regression was done to assess the associations between obesity and CHD. The mean age was 53.1 +/ 8.3 for men and 51.9 +/- 8.4 for women. After adjustment for confounders the odds ratio (OR) of CHD for men was 1.69 (95% CI, 1.24-2.32), 1.94 (95% CI 1.40 2.70), and 1.32 (95% CI, 1.01-2.16) per 1 standard deviation (SD) increase in BMI, WC, and WHtR respectively. The OR for women was 2.64 (CI, 1.61-4.34), 1.82 (95% CI 1.12-2.95), 2.32 (95% CI, 1.36-3.96), and 1.94 (95% CI, 1.23-3.07) per 1 SD increase in BMI, WC, WHtR and WHR respectively. Since both total obesity and abdominal adiposity were associated with development of CHD and since measurement of WC and BMI are inexpensive, both should be included in the clinical setting for CHD risk assessment for this group of population. PMID- 26550485 TI - Effect of Malathion on Reproductive Parameters of Engorged Female Rhipicephalus (Boophilus) microplus Ticks of Punjab Districts, India. AB - The present study was aimed at evaluating effects of malathion on the various reproductive parameters, namely, egg mass weight (EMW), reproductive index (RI), percentage inhibition of oviposition (%IO), and hatchability percentage of eggs of Rhipicephalus (Boophilus) microplus (Canestrini 1887) females from 19 districts of Punjab, India. The effect on various parameters was found to be dose dependent and more discernible upon exposure to higher concentrations. Complete cessation of egg laying was recorded in tick isolates on exposure to 5000 ppm and above. The values of %IO ranged in 4.4-68.6, 25.2-76.2, 35.6-100.0, 45.7-100.0, and 71.4-100.0 in groups treated with 1250, 2500, 5000, 10000, and 20000 ppm of malathion, respectively. A low hatching % was recorded in eggs of all treated female ticks in comparison to control treated with distilled water and complete inhibition of hatching was recorded at 10000 ppm and above. However, the survival of the hatched larvae was not affected and was similar to control group. The results of the current study can be of immense help in formulation and implementation of effective tick control measures. PMID- 26550486 TI - Comment on "Extraction of Iron from the Rabbit Anterior Chamber with Reverse Iontophoresis". PMID- 26550487 TI - A Comparative Study between Vitrectomy with Internal Tamponade and a New Modified Fiber Optic Illuminated Ando Plombe for Cases of Macular Hole Retinal Detachment in Myopic Eyes. AB - Aim. To compare pars plana vitrectomy (PPV) with silicone tamponade or gas (Groups Ia and Ib) and a new modified Ando plombe equipped with a fiber optic light (Group II) for cases with macular hole retinal detachment (MHRD) in high myopic eyes (axial length > 26 mm). Methods. A prospective interventional randomized case series included 60 eyes (20 in each group). Successful outcome was considered if the retina was completely attached at the end of the follow-up period. Complications were identified for each group. Results. Visual acuity improved by 37.31%, 40.67%, and 49.40% in Groups Ia, Ib, and II, respectively. The success rate was 55%, 60%, and 100% in Groups Ia , Ib, and II, respectively, with a statistically significant difference between Groups Ia, Ib, and II (p < 0.001 in Ia, p: 0.002 in Ib). Complications rates were 60%, 45%, and 20% in Groups Ia, Ib, and II, respectively, with a statistically significant difference between Groups Ia and II (p: 0.01). Conclusion. Fiber optic illuminated Ando plombe allows better positioning under the macula and consequently improves the success rate of epimacular buckling in comparison to PPV with internal tamponade in MMHRD. PMID- 26550488 TI - A Concept Mapping Study of Physicians' Perceptions of Factors Influencing Management and Control of Hypertension in Sub-Saharan Africa. AB - Hypertension, once a rare problem in Sub-Saharan Africa (SSA), is predicted to be a major cause of death by 2020 with mortality rates as high as 75%. However, comprehensive knowledge of provider-level factors that influence optimal management is limited. The objective of the current study was to discover physicians' perceptions of factors influencing optimal management and control of hypertension in SSA. Twelve physicians attending the Cardiovascular Research Training (CaRT) Institute at the University of Ghana, College of Health Sciences, were invited to complete a concept mapping process that included brainstorming the factors influencing optimal management and control of hypertension in patients, sorting and organizing the factors into similar domains, and rating the importance and feasibility of efforts to address these factors. The highest ranked important and feasible factors include helping patients accept their condition and availability of adequate equipment to enable the provision of needed care. The findings suggest that patient self-efficacy and support, physician-related factors, policy factors, and economic factors are important aspects that must be addressed to achieve optimal hypertension management. Given the work demands identified by physicians, future research should investigate cost-effective strategies of shifting physician responsibilities to well-trained no-physician clinicians in order to improve hypertension management. PMID- 26550489 TI - Provider Adherence to National Guidelines for Managing Hypertension in African Americans. AB - Purpose. To evaluate provider adherence to national guidelines for the treatment of hypertension in African Americans. Design. A descriptive, preexperimental, quantitative method. Methods. Electronic medical records were reviewed and data were obtained from 62 charts. Clinical data collected included blood pressure readings, medications prescribed, laboratory studies, lifestyle modification, referral to hypertension specialist, and follow-up care. Findings. Overall provider adherence was 75%. Weight loss, sodium restriction, and physical activity recommendations were documented on 82.3% of patients. DASH diet and alcohol consumption were documented in 6.5% of participants. Follow-up was documented in 96.6% of the patients with controlled blood pressure and 9.1% in patients with uncontrolled blood pressure. Adherence in prescribing ACEIs in patients with a comorbidity of DM was documented in 70% of participants. Microalbumin levels were ordered in 15.2% of participants. Laboratory adherence prior to prescribing medications was documented in 0% of the patients and biannual routine labs were documented in 65% of participants. Conclusion. Provider adherence overall was moderate. Despite moderate provider adherence, BP outcomes and provider adherence were not related. Contributing factors that may explain this lack of correlation include patient barriers such as nonadherence to medication and lifestyle modification recommendations and lack of adequate follow up. Further research is warranted. PMID- 26550490 TI - Single Tablet Regimen Usage and Efficacy in the Treatment of HIV Infection in Australia. AB - Single tablet regimens (STRs) for HIV infection improve patient satisfaction, quality of life, medication adherence, and virological suppression compared to multitablet regimens (MTRs). This is the first study assessing STR uptake and durability in Australia. This retrospective audit of all patients receiving an STR (n = 299) at a large Sydney HIV clinic (January 2012-December 2013) assessed patient demographics, treatment prior to STR, HIV RNA load and CD4 during MTR and STR dosing, and reasons for STR switch. 206 patients switched from previous antiretroviral treatment to an STR, of which 88% switched from an MTR. Reasons for switching included desire to simplify treatment (57%), reduced side effects or toxicity (18%), and cost-saving for the patient. There was no switching for virological failure. Compared to when on an MTR, patients switching to an STR had significantly lower HIV RNA counts (p < 0.001) and significantly higher CD4 counts (p < 0.001). The discontinuation rate from STR was very low and all patients who switched to an STR maintained virological suppression throughout the study duration, although the study is limited by the absence of a control group. PMID- 26550491 TI - Influence of Moxifloxacin on Hepatic Redox Status and Plasma Biomarkers of Hepatotoxicity and Nephrotoxicity in Rat. AB - Moxifloxacin is a broad spectrum fluoroquinolone antibacterial agent. We examined the hepatic redox status and plasma biomarkers of nephrotoxicity and hepatotoxicity in rat following administration of moxifloxacin (MXF). Twenty-four Wistar rats, 180-200 g, were randomized into four groups (I-IV). Animals in group I (control) received 1 mL of distilled water, while animals in groups II, III, and IV received 1 mL each of MXF equivalent to 4 mg/kg b.w., 8 mg/kg b.w., and 16 mg/kg b.w., respectively. After seven days, plasma urea, bilirubin, and creatinine were significantly (P < 0.05) elevated in the MXF-treated animals. Activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were significantly increased in the plasma of MXF-treated animals compared to control. Also plasma total cholesterol, HDL-cholesterol, LDL cholesterol, and triglycerides increased significantly in the MXF-treated groups relative to control. Moreover, MXF triggered a significant decrease in hepatic catalase, superoxide dismutase, and glutathione-S transferase activities. Likewise, MXF caused a decrease in the hepatic levels of glutathione and vitamin C. A significant increase in hepatic MDA content was also observed in the MXF treated animals relative to control. Overall, our data suggest that the half therapeutic, therapeutic, and twice the therapeutic dose of MXF induced nephrotoxicity, hepatotoxicity, and altered hepatic redox balance in rats. PMID- 26550492 TI - AngiomiRs: Potential Biomarkers of Pregnancy's Vascular Pathologies. AB - In recent years, microRNAs (miRNAs) have been the focus of research for their role in posttranscriptional regulation and as potential biomarkers of risk for disease development. Their identification in specific physiological processes, like angiogenesis, a key pathway in placental vascular development in pregnancy, suggests an important role of miRNAs that regulate angiogenesis (angiomiRs). Many complications of pregnancy have in common placental vascular alterations, involving an imbalance in the angiogenesis process in the development of conditions such as preeclampsia, intrauterine growth restriction, and gestational diabetes, complications with the highest rates of morbimortality in pregnancy. Many studies have identified angiomiRs with differential expression profiles in each of these diseases; however, this evidence requires further studies focused on evaluating their potential as biomarkers of risk for the angiomiRs detected, to establish correlations between placental tissue and serum/plasma expression profiles. Therefore, the objective of this review is to highlight the best angiomiRs detected in placental tissue and serum/plasma in each of these three pathologies to show the current data available for potential biomarkers and to propose future research strategies on this topic. PMID- 26550493 TI - Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis. AB - Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60-89 mL/min/1.73 m(2). Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was >=90, 60-89, and 30-59 mL/min/1.73 m(2) in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI. PMID- 26550494 TI - Cardiac Implantable Electronic Device Infection: From an Infection Prevention Perspective. AB - A cardiac implantable electronic device (CIED) is indicated for patients with severely reduced ejection fraction or with life-threatening cardiac arrhythmias. Infection related to a CIED is one of the most feared complications of this life saving device. The rate of CIED infection has been estimated to be between 2 and 25; though evidence shows that this rate continues to rise with increasing expenditure to the patient as well as healthcare systems. Multiple risk factors have been attributed to the increased rates of CIED infection and host comorbidities as well as procedure related risks. Infection prevention efforts are being developed as defined bundles in numerous hospitals around the country given the increased morbidity and mortality from CIED related infections. This paper aims at reviewing the various infection prevention measures employed at hospitals and also highlights the areas that have relatively less established evidence for efficacy. PMID- 26550495 TI - Eating Behaviours of British University Students: A Cluster Analysis on a Neglected Issue. AB - Unhealthy diet is a primary risk factor for noncommunicable diseases. University student populations are known to engage in health risking lifestyle behaviours including risky eating behaviours. The purpose of this study was to examine eating behaviour patterns in a population of British university students using a two-step cluster analysis. Consumption prevalence of snack, convenience, and fast foods in addition to fruit and vegetables was measured using a self-report "Student Eating Behaviours" questionnaire on 345 undergraduate university students. Four clusters were identified: "risky eating behaviours," "mixed eating behaviours," "moderate eating behaviours," and "favourable eating behaviours." Nineteen percent of students were categorised as having "favourable eating behaviours" whilst just under a third of students were categorised within the two most risky clusters. Riskier eating behaviour patterns were associated with living on campus and Christian faith. The findings of this study highlight the importance of university microenvironments on eating behaviours in university student populations. Religion as a mediator of eating behaviours is a novel finding. PMID- 26550497 TI - Boerhaave Syndrome, Pneumothorax, and Chylothorax in a Critically Ill Patient with Tuberous Sclerosis Complex. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant, variably expressed multisystem disease. The predominant pulmonary features of TSC are identical to those of lymphangioleiomyomatosis (LAM). Pneumothorax, multifocal micronodular pneumocyte hyperplasia, and chylothorax are rare complications of TSC. We report a young male with pneumothorax, lung nodules, and chylous effusion who developed empyema thoracis after esophageal rupture. Hospital course was complicated by respiratory failure. Family opted to transfer to hospice care. Chylothorax is a rare complication of TSC with few scattered reports mostly in female patients. Patients with TSC are usually managed by multispecialists and it is important to be aware of the rare pulmonary manifestations of this disease. A male patient with TSC having lung nodules presenting with chylothorax and empyema thoracis from Boerhaave syndrome makes our case unique. PMID- 26550496 TI - Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats. AB - Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair. PMID- 26550498 TI - Delirium Accompanied by Cholinergic Deficiency and Organ Failure in a 73-Year-Old Critically Ill Patient: Physostigmine as a Therapeutic Option. AB - Delirium is a common problem in ICU patients, resulting in prolonged ICU stay and increased mortality. A cholinergic deficiency in the central nervous system is supposed to be a relevant pathophysiologic process in delirium. Acetylcholine is a major transmitter of the parasympathetic nervous system influencing several organs (e.g., heart and kidneys) and the inflammatory response too. This perception might explain that delirium is not an individual symptom, but rather a part of a symptom complex with various disorders of the whole organism. The cholinergic deficiency could not be quantified up to now. Using the possibility of bedside determination of the acetylcholinesterase activity (AChE activity), we assumed to objectify the cholinergic homeostasis within minutes. As reported here, the postoperative delirium was accompanied by a massive hemodynamic and renal deterioration of unclear genesis. We identified the altered AChE activity as a plausible pathophysiological mechanism. The pharmacological intervention with the indirect parasympathomimetic physostigmine led to a quick and lasting improvement of the patient's cognitive, hemodynamic, and renal status. In summary, severe delirium is not always an attendant phenomenon of critical illness. It might be causal for multiple organ deterioration if it is based on cholinergic deficiency and has to be treated at his pathophysiological roots whenever possible. PMID- 26550499 TI - Empedobacter brevis Bacteremia in a Patient Infected with HIV: Case Report and Review of Literature. AB - Clinical disease caused by Empedobacter brevis (E. brevis) is very rare. We report the first case of E. brevis bacteremia in a patient with HIV and review the current literature. A 69-year-old man with human immunodeficiency virus (HIV) and CD4 count of 319 presented with chief complaints of black tarry stools, nausea and vomiting for 2 days. Physical exam was significant for abdominal pain on palpation with no rebound or guarding. His total leukocyte count was 32,000 cells/MUL with 82% neutrophils and 9% bands. Emergent colonoscopy and endoscopic esophagogastroduodenoscopy showed esophageal candidiasis, a nonbleeding gastric ulcer, and diverticulosis. Blood cultures drawn on days 1, 2, and 3 of hospitalization grew E. brevis. Patient improved with intravenous antibiotics. This case is unusual, raising the possibility of gastrointestinal colonization as a source of the patient's bacteremia. In conclusion, E. brevis is an emerging pathogen that can cause serious health care associated infections. PMID- 26550500 TI - Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids. AB - The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity. PMID- 26550501 TI - An Unexpected Cause of Severe Hypokalemia. AB - We describe an unusual case of severe hypokalemia with electrocardiographic changes, due to licorice consumption, in a 15-year-old female student with no previous medical history. Prompt replacement of potassium and cessation of licorice ingestion resulted in a favourable outcome. We also discuss the pathophysiology and diagnosis, emphasizing the importance of a detailed anamnesis to rule out an often forgotten cause of hypokalemia as the licorice poisoning. PMID- 26550502 TI - Focal (123)I-FP-CIT SPECT Abnormality in Midbrain Vascular Parkinsonism. AB - Cerebrovascular diseases are considered among possible causes of acute/subacute parkinsonism, representing up to 22% of secondary movement disorders. In cases of suspected vascular parkinsonism (VP), dopamine transporter SPECT has been highly recommended to exclude nigrostriatal dopaminergic degeneration. We report the case of a hemiparkinsonism related to a left midbrain infarct with focal lateralized putaminal abnormalities at (123)I-FP-CIT SPECT imaging. The asymmetric uptake at dopamine transporter SPECT was different to findings commonly observed in typical PD pattern, because the ipsilateral striatum, in opposite to idiopathic PD, showed normal tracer binding. However, this selective parkinsonism after infarction of the midbrain was responsive to levodopa. In conclusion, we retain that there is a need of more functional imaging studies in VP addressed to a more consistent classification of its different clinical forms and to a better understanding of the adequate pharmacological management. PMID- 26550503 TI - CPAP Therapy Improves Intractable Hemifacial Spasm. AB - The correlation between obstructive sleep apnea (OSA) and hemifacial spasm has never been reported in the literature. Here, we report a case of OSA-induced hypertension with intractable hemifacial spasm in which both conditions improved after continuous positive airway pressure treatment. PMID- 26550504 TI - An Unusual Case of Invasive Kaposi's Sarcoma with Primary Effusion Lymphoma in an HIV Positive Patient: Case Report and Literature Review. AB - We report a case of AIDS-related Kaposi's sarcoma (KS) with Primary Effusion Lymphoma (PEL) in a 28-year-old, African American male. Kaposi's sarcoma is an AIDS defining disease and typically will disseminate early in the course of the disease affecting the skin, mucous membranes, gastrointestinal tract, lymph nodes, and lungs. This case reports an unusual presentation of the disease along with primary effusion lymphoma. Although the most common organ systems affected by KS are the respiratory and the gastrointestinal systems, the lungs of this patient did not show any evidence of KS. Additionally, the patient demonstrates the rarely seen liver and unique pancreatic involvement by KS along with unusual synchronous bilateral pleural and peritoneal cavity involvement by PEL, adding to the distinct pattern of invasive AIDS-related Kaposi's sarcoma. PMID- 26550505 TI - Is It Safe to Restart Antivascular Endothelial Growth Factor Therapy in Patients with Renal Cell Carcinoma after Cardiac Ischemia? AB - Agents targeting vascular endothelial growth factor (VEGF) represent active drugs in treating patients with advanced renal cell carcinoma (RCC). Studies have shown that sunitinib and axitinib can be associated with cardiac toxicity. Whether these agents should be restarted in patients who experience cardiac ischemia remains uncertain. Here, we present three patients with metastatic RCC who restarted sunitinib or axitinib after intervention of active ischemic cardiac disease without causing subsequent relevant cardiac events. This experience suggests that these agents can be continued after management of cardiac ischemia. PMID- 26550506 TI - Mucoepidermoid Carcinoma of the Palatine Tonsil. AB - Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy in both adults and children. It has a slight female predilection and usually presents as a painless, rubber-like or soft mass, which may be fixed or mobile. Histologically, MEC is comprised of a mixture of cell types including mucous, epidermoid, and intermediate cells that can be arranged in solid nests or cystic structures. In the oral cavity, it most frequently occurs at the palate or buccal mucosa. The present paper aimed to describe an unusual case of MEC arising in the palatine tonsil. PMID- 26550507 TI - Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen. AB - Optic disc drusen (ODD) are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION) who received the diagnosis of bilateral optic disc drusen five years earlier and thereby reiterated the association of ODD and acute NAION. PMID- 26550508 TI - Medical and Surgical Treatment in Pediatric Orbital Myositis Associated with Coxsackie Virus. AB - Purpose. To report a case of orbital myositis associated with Coxsackie virus and its medical and surgical approach. Methods. Complete ophthalmological examination and imaging and analytical investigation were performed. Results. A 6-year-old male presented with subacute painless binocular horizontal diplopia. Examination revealed bilateral best-corrected visual acuity (BCVA) of 20/20 and right eye 45 prism-dioptre (PD) esotropia in near and distance fixations, with no motility restrictions. Serologic screening was positive for Coxsackie virus acute infection and computerized tomography (CT) suggested right eye medial rectus orbital myositis. An oral corticosteroid 1.0 mg/kg/day regimen was started. A new CT after two months showed symmetrical lesions in both medial rectus muscles. Corticosteroids were increased to 1.5 mg/kg/day. After imagiological resolution on the 4th month, alternating 45 PD esotropia persisted. Bilateral 7 mm medial rectus recession was performed after 1 year without spontaneous recovery. At 1 year follow-up, the patient is orthophoric with 200'' stereopsis and bilateral 20/20 BCVA. Conclusions. To our knowledge, this is the first reported case of orbital myositis associated with Coxsackie virus. This is also the first reported case of isolated strabismus surgery after orbital myositis in pediatric age, highlighting the favourable aesthetic and functional outcomes even in cases of late ocular motility disorders. PMID- 26550509 TI - Uncommon Variant of Type II Monteggia Fracture with Concomitant Distal Humeral Fracture. AB - Monteggia fracture-dislocation, a common injury sustained by pediatric population, is a rare entity in adults. It was first observed by Giovanni Battista Monteggia and later classified by Bado into 4 groups. The term "Monteggia equivalent or variant" was introduced to describe certain injuries with similar radiographic pattern and biomechanism of injury. Since then various types and their variants have been described in the literature. We present a complex fracture pattern in a 55-year-old male not previously described in the literature along with its treatment modality and favorable outcome. PMID- 26550510 TI - Detached Anterior Horn of the Medial Meniscus Mimicking a Parameniscal Cyst. AB - We report a case of a detached anterior horn of the medial meniscus with anterior knee pain. Preoperative magnetic resonance images of the knee were initially interpreted as a parameniscal cyst. Arthroscopic examination revealed subluxation of the anterior horn of the medial meniscus due to detachment from its anterior tibial insertion. Arthroscopic fixation with a suture anchor was successful and the cystic lesion was no longer visible on postoperative images. PMID- 26550511 TI - Follicular Thyroid Carcinoma Metastatic to the Kidney: Report of a Case with Cytohistologic Correlation. AB - Here we report a case of a 45-year-old female who underwent thyroidectomy for thyroid cancer and presented 20 years later with a left renal mass. CT-guided core biopsy was performed, and imprints and histologic sections of the biopsy showed cells resembling thyroid follicular cells with a background containing colloid. Immunohistochemistry revealed positivity for thyroglobulin and thyroid transcription factor 1, consistent with metastatic follicular thyroid carcinoma (FTC). The patient later underwent radical nephrectomy; histologic sections of the resected tumor revealed an encapsulated lesion morphologically similar to the biopsy specimen. Thyroid metastases to the kidney are extremely rare and are often detected during postthyroidectomy surveillance by elevation in thyroid hormone levels, (131)I scintigraphy, or (18)F-fluorodeoxyglucose uptake in positron emission tomography studies. Treatment involves total thyroidectomy, resection of the metastatic foci, and (131)I therapy. The differential diagnoses of renal metastasis of FTC include the encapsulated follicular variant of papillary thyroid carcinoma (PTC), which possesses some of the nuclear features seen in conventional PTC but may occasionally be indistinguishable from FTC in cytologic preparations, and renal lesions such as benign thyroidization of the kidney and thyroid-like follicular carcinoma of the kidney, which mimic FTC in histologic appearance but do not stain with thyroid markers. PMID- 26550512 TI - Corrigendum to "Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism". PMID- 26550513 TI - Radiographic Thrombus within the External Jugular Vein: Report of a Rare Case and Review of the Literature. AB - We are reporting a case of a 91-year-old male with a primary malignancy of the right parotid gland with radiographic thrombus extension within the right external jugular vein. He was treated with palliative radiation therapy to the right parotid mass with a marked clinical response. The rarity of this occurrence as documented in the review of the literature provides for uncertainty with regard to proper management. Radiographic evidence of thrombus in the absence of clinical manifestations, the role of anticoagulation, and the proper radiation target delineation were all challenges encountered in the care of this patient. Our case represents a rare occurrence with unique radiologic findings that has implications for management. PMID- 26550514 TI - An Unusual Association: Iliopsoas Bursitis Related to Calcium Pyrophosphate Crystal Arthritis. AB - A 71-year-old man with osteoarthritis and chondrocalcinosis came to our observation developing a swelling in the groin region after a recent left colectomy for adenocarcinoma. The imaging techniques revealed the presence of an iliopsoas bursitis in connection with the hip. The synovial fluid analysis detected the presence of calcium pyrophosphate (CPP) crystals and allowed the final and unusual diagnosis of iliopsoas bursitis related to acute CPP crystal hip arthritis. PMID- 26550515 TI - A Rare Complication of Composite Dual Mesh: Migration and Enterocutaneous Fistula Formation. AB - Introduction. Mesh is commonly employed for abdominal hernia repair because it ensures a low recurrence rate. However, enterocutaneous fistula due to mesh migration can occur as a very rare, late complication, for which diagnosis is very difficult. Presentation of Case. Here we report the case of an enterocutaneous fistula due to late mesh migration in a mentally retarded, diabetic, 35-year-old male after umbilical hernia repair with composite dual mesh in 2010. Discussion. Mesh is a foreign substance, because of that some of the complications including hematoma, seroma, foreign body reaction, organ damage, infection, mesh rejection, and fistula formation may occur after implantation of the mesh. In the literature, most cases of mesh-associated enterocutaneous fistula due to migration involved polypropylene meshes. Conclusion. This case serves as a reminder of migration of composite dual meshes. PMID- 26550516 TI - A Case of Pneumococcal Peritonitis after Caesarean Section in a Healthy Woman. AB - Pneumococcal peritonitis is prevalent in children and adults with comorbidities but extremely rare in healthy adults. Here we describe a case of pneumococcal peritonitis in a previously healthy woman with no known risk factors who presented with constipation, abdominal pain, and distention. Her only past medical history was an uncomplicated C-section two months prior to presentation. A laparotomy revealed a pneumococcal peritonitis without visible source of infection. The patient remained hospitalized until completion of antibiotic regimen with Ceftriaxone and resolution of symptoms. This report adds to the small body of evidence showing possible pneumococcal peritonitis in healthy young adults. PMID- 26550517 TI - Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands). AB - Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions. PMID- 26550519 TI - Diagnosis of Obstructive Sleep Apnea in Parkinson's Disease Patients: Is Unattended Portable Monitoring a Suitable Tool? AB - Purpose. Obstructive sleep apnea (OSA) is frequent in Parkinson's disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD. Methods. Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n = 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds. Results. Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction. Conclusion. PM was adequate to "rule in" moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction. PMID- 26550518 TI - Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted? AB - Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a "nerve mast cell-myofibroblast axis" in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions. PMID- 26550520 TI - Characterization of Nutritional Composition, Antioxidative Capacity, and Sensory Attributes of Seomae Mugwort, a Native Korean Variety of Artemisia argyi H. Lev. & Vaniot. AB - Few studies have investigated Seomae mugwort (a Korean native mugwort variety of Artemisia argyi H. Lev. & Vaniot), exclusively cultivated in the southern Korean peninsula, and the possibility of its use as a food resource. In the present study, we compared the nutritional and chemical properties as well as sensory attributes of Seomae mugwort and the commonly consumed species Artemisia princeps Pamp. In comparison with A. princeps, Seomae mugwort had higher contents of polyunsaturated fatty acids, total phenolic compounds, vitamin C, and essential amino acids. In addition, Seomae mugwort had better radical scavenging activity and more diverse volatile compounds than A. princeps as well as favorable sensory attributes when consumed as tea. Given that scant information is available regarding the Seomae mugwort and its biological, chemical, and sensory characteristics, the results herein may provide important characterization data for further industrial and research applications of this mugwort variety. PMID- 26550521 TI - Antifungal Effect of Lavender Essential Oil (Lavandula angustifolia) and Clotrimazole on Candida albicans: An In Vitro Study. AB - Background. The treatment of candidiasis infections is an important problem in the health care system. This study aimed to investigate the in vitro effect of lavender essential oil and clotrimazole on isolated C. albicans from vaginal candidiasis. Materials and Methods. In this clinical trial, C. albicans isolated from the vaginal discharge samples was obtained. Results. The pairwise comparison showed that lavender and clotrimazole had a significant difference; this difference in the lavender group was lower than clotrimazole. But, after 48 hours, there was no difference seen between groups. There was a significant difference between clotrimazole and DMSO groups. Comparing the changes between groups based on the same dilution, at 24 h and 48 h in clotrimazole group, showed a significant difference two times in the fungal cell count that its average during 48 h was less than 24 h. A significant difference was observed between the two periods in lavender group, only at the dilutions of 1/20 and 1/80. The average fungal cell count after 48 h was also lower in lavender group. Conclusions. Given that the lavender has antifungal activity, this can be used as an antifungal agent. However, more clinical studies are necessary to validate its use in candida infection. PMID- 26550522 TI - Perceptions of Nigerian Women about Human Papilloma Virus, Cervical Cancer, and HPV Vaccine. AB - Background. Cervical cancer caused by human papilloma virus (HPV) though preventable has claimed the lives of many women worldwide. This study was embarked upon to evaluate the general knowledge and perceptions of Nigerian women on HPV, cervical cancer, and HPV vaccine. Methods. Structured questionnaires were administered to a cross section of 737 women randomly selected from the general population in two southwestern States of Nigeria. Statistical analysis was done using SPSS computer software version 16. A P value >0.05 was considered statistically significant. Results. One hundred and seventy-six (23.9%) of the respondents had knowledge of HPV; 474 (64.3%) are aware of cervical cancer but only 136 (18.5%) know that HPV causes cervical cancer. 200 (27.1%) are aware that there is an HPV vaccine while 300 (40.7%) had knowledge of Pap smear test. Two hundred and sixty (35.3%) of the respondents know that early detection of HPV can prevent cervical cancer and in spite of this, only 110 (14.9%) have taken the Pap smear test before while 151 (20.5%) are not willing to go for the test at all. Conclusions. There is therefore the need to create proper awareness on the HPV and its possible consequence of cervical carcinoma. PMID- 26550523 TI - Welcoming a global microbiome initiative proposal for precision dentistry. PMID- 26550524 TI - Assessment of buccal bone thickness of aesthetic maxillary region: a cone-beam computed tomography study. AB - PURPOSE: The aim of this study was to analyze the anatomical dimensions of the buccal bone walls of the aesthetic maxillary region for immediate implant placement, based upon cone-beam computed tomography (CBCT) scans in a sample of adult patients. METHODS: Two calibrated examiners analyzed a sample of 50 CBCT scans, performing morphometric analyses of both incisors and canines on the left and right sides. Subsequently, in the sagittal view, a line was traced through the major axis of the selected tooth. Then, a second line (E) was traced from the buccal to the palatal wall at the level of the observed bone ridges. The heights of the buccal and palatal bone ridges were determined at the major axis of the tooth. The buccal bone thickness was measured across five lines. The first was at the level of line E. The second was at the most apical point of the tooth, and the other three lines were equidistant between the apical and the cervical lines, and parallel to them. Statistical analysis was performed with a significance level of P<=0.05 for the bone thickness means and standard deviations per tooth and patient for the five lines at varying depths. RESULTS: The means of the buccal wall thicknesses in the central incisors, lateral incisors and canines were 1.14+/-0.65 mm, 0.95+/-0.67 mm and 1.15+/-0.68 mm, respectively. Additionally, only on the left side were significant differences in some measurements of buccal bone thickness observed according to age and gender. However, age and gender did not show significant differences in heights between the palatal and buccal plates. In a few cases, the buccal wall had a greater height than the palatal wall. CONCLUSIONS: Less than 10% of sites showed more than a 2-mm thickness of the buccal bone wall, with the exception of the central incisor region, wherein 14.4% of cases were >=2 mm. PMID- 26550525 TI - Peri-implant crevicular fluid levels of cathepsin-K, RANKL, and OPG around standard, short, and mini dental implants after prosthodontic loading. AB - PURPOSE: Despite the high success rates of endosseous dental implants, their placement is restricted according to the height and volume of bone available. The use of short or mini dental implants could be one way to overcome this limitation. Thus, this study aimed to compare standard, short, and mini dental implants with regard to associated clinical parameters and peri-implant crevicular fluid (PICF) levels of cathepsin -K (CTSK), RANK ligand (RANKL), and osteoprotegerin (OPG), after prosthodontic loading. METHODS: A total of 78 non submerged implants (Euroteknika, Aesthetica(+2), Sallanches, France) were installed in 30 subjects (13 male, 17 female; range, 26-62 years) who visited the clinic of the Periodontology Department, Faculty of Dentistry, Selcuk University. Sampling and measurements were performed on the loading date (baseline) and 2, 14, and 90 days after loading. Assessment of the peri-implant status for the implant sites was performed using the pocket probing depth (PPD), modified plaque index, modified gingival index, modified sulcular bleeding index, and radiographic signs of bone loss. PICF samples collected from each implant were evaluated for CTSK, RANKL, and OPG levels using the ELISA method. Keratinized tissue and marginal bone loss (MBL) were also noted. RESULTS: Clinical parameters statistically significantly increased in each group but did not show statistical differences between groups without PPD. Although implant groups showed a higher MBL in the upper jaw, only the standard dental group demonstrated a statistically significant difference. At 90 days, the OPG: sRANKL ratio and total amounts of CTSK for each group did not differ from baseline. CONCLUSIONS: Within the limitations of this study, both short and mini dental implants were achieving the same outcomes as the standard dental implants in the early period after loading. PMID- 26550526 TI - Humoral immune responses to periodontal pathogens in the elderly. AB - PURPOSE: Elderly people are thought to be more susceptible to periodontal disease due to reduced immune function associated with aging. However, little information is available on the nature of immune responses against putative periodontal pathogens in geriatric patients. The purpose of this study was to evaluate the serum IgG antibody responses to six periodontal pathogens in geriatric subjects. METHODS: The study population consisted of 85 geriatric patients and was divided into three groups: 29 mild (MCP), 27 moderate (MoCP) and 29 severe (SCP) chronic periodontitis patients. Serum levels of IgG antibody to Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Prevotella intermedia were measured by enzyme-linked immunosorbent assay (ELISA) and compared among the groups. RESULTS: All three groups showed levels of serum IgG in response to P. gingivalis, A. actinomycetemcomitans, and P. intermedia that were three to four times higher than levels of IgG to T. forsythia, T. denticola, and F. nucleatum. There were no significant differences among all three groups in IgG response to P. gingivalis (P=0.065), T. forsythia (P=0.057), T. denticola (P=0.1), and P. intermedia (P=0.167), although the IgG levels tended to be higher in patients with SCP than in those with MCP or MoCP (with the exception of those for P. intermedia). In contrast, there were significant differences among the groups in IgG levels in response to F. nucleatum (P=0.001) and A. actinomycetemcomitans (P=0.003). IgG levels to A. actinomycetemcomitans were higher in patients with MCP than in those with MoCP or SCP. CONCLUSIONS: When IgG levels were compared among three periodontal disease groups, only IgG levels to F. nucleatum significantly increased with the severity of disease. On the contrary, IgG levels to A. actinomycetemcomitans decreased significantly in patients with SCP compared to those with MCP. There were no significant differences in the IgG levels for P. gingivalis, T. forsythia, T. denticola, and P. intermedia among geriatric patients with chronic periodontitis. PMID- 26550527 TI - Effect of root planing on the reduction of probing depth and the gain of clinical attachment depending on the mode of interproximal bone resorption. AB - PURPOSE: The purpose of the present study was to evaluate the effect of root planing on the reduction of probing pocket depth and the gain of clinical attachment depending on the pattern of bone resorption (vertical versus horizontal bone loss) in the interproximal aspect of premolar teeth that showed an initial probing pocket depth of 4-6 mm. METHODS: In this study, we analyzed 68 teeth (15 from the maxilla and 53 from the mandible) from 32 patients with chronic periodontitis (17 men and 15 women; mean age, 53.6 years). The probing pocket depth and clinical attachment level at all six sites around each tooth were recorded before treatment to establish a baseline value, and then three months and six months after root planing. RESULTS: The reduction in interdental pocket depth was 1.1 mm in teeth that experienced horizontal bone loss and 0.7 mm in teeth that experienced vertical bone loss. Interdental attachment was increased by 1.0 mm in teeth with horizontal bone loss and by 0.7 mm in teeth with vertical bone loss. The reduction of probing pocket depth and the gain of clinical attachment occurred regardless of defect patterns three and six months after root planing. CONCLUSIONS: The reduction of pocket depth and gain in the clinical attachment level were significantly larger in horizontally patterned interproximal bone defects than in vertical bone defects. PMID- 26550528 TI - New targets for controlling Ebola virus disease. PMID- 26550529 TI - Intracerebral hemorrhage revealing a Cushing's disease. AB - Secondary hypertension related to endocrine disease is uncommon. Here, we report a case of hypertensive intracerebral hemorrhage associated with Cushing's disease. PMID- 26550530 TI - The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction. AB - OBJECTIVE: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. BACKGROUND: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. MATERIAL AND METHODS: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. RESULTS: QTc max. interval, QTc dispersion and Tpeak Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24+/-14.7 ms vs. 433.55+/-14.4 ms, P<0.000; 44.98+/-18.78 ms vs. 32.05+/-17.9 ms, P<0.000; 32.60+/-1.6 ms vs. 17.46+/-2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). CONCLUSION: The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization. PMID- 26550531 TI - Multivariate analysis of the volumetric capnograph for PaCO2 estimation. AB - PURPOSE: End-tidal CO2 (eTCO2) can be used to estimate the arterial CO2 (PaCO2) under steady-state conditions, but that relationship deteriorates during hemodynamic or respiratory instability. We developed a multivariate method to improve our ability to estimate the PaCO2, by using additional information contained in the volumetric capnograph (Vcap) waveform. We tested this approach using data from a porcine model of chest trauma/hemorrhage. METHODS: This experiment consisted of 3 stages: pre-injury, injury/resuscitation, and post injury. In stage I, anesthetized pigs (n=26) underwent ventilator maneuvers (tidal volume and respiratory rate) to induce hypo-or hyper-ventilation. In stage II, pigs underwent either (A) unilateral pulmonary contusion, hemorrhage, and resuscitation (n=13); or (B) bilateral pulmonary contusion (n=13) followed by 30 min of monitoring. In stage III, the ventilator maneuvers were repeated. The following Vcap features were measured: eTCO2, phase 2 slope (p2m), phase 3 slope (p3m), and inter-breath interval. The data were fit to 2 models: (1) multivariate linear regression and (2) a machine-learning model (M5P). RESULTS: 1750 10-breath sets were analyzed. Univariate models employing eTCO2 alone were adequate during stages I and III. During stage II, mean error for the linear model was -8.44 mmHg (R(2)=0.14, P<0.001) and for M5P it was -5.98 mmHg (R(2)=0.13, P<0.01). By adding Vcap features, all models exhibited improvement. In stage II, the mean error of the linear model improved to -4.64 mmHg (R(2)=0.11, P<0.01), and that of the M5P model improved to -1.62 mmHg (R(2)=0.25, P<0.01). CONCLUSIONS: By incorporating Vcap waveform features, multivariate methods modestly improved PaCO2 estimation, especially during periods of hemodynamic and respiratory instability. Further work would be needed to produce a clinically useful CO2 monitoring system under these challenging conditions. PMID- 26550532 TI - Shivlilik burns: injuries resulting from traditional celebrations. AB - INTRODUCTION: In Konya, Turkey, the community celebrates the traditional ceremony of Shivlilik, which occurs on the first day of the seventh month in the lunar based Hijri calendar. In the evening, people light bonfires of tires in the streets, and children and young people attempt to jump over the flames. Flame burns regularly occur due to falling. Attention should be given to preventing injuries such as these that are caused by social and regional customs. METHODS: This retrospective study was carried out using data from the Konya Education and Research Hospital Burn Unit. Patients admitted to our hospital between June, 2009, and May, 2012, was evaluated. RESULTS: Eleven patients were admitted to hospital with flame burns caused by jumping over fires on the days when the traditional Shivlilik ceremony was celebrated. The clinical data evaluated included the patient's age and sex, the depth of the burn injury, the total burned surface area (TBSA), and the distribution of the burn areas. CONCLUSIONS: Serious flame burns occur because of the traditional Shivlilik ceremony. We must promote some changes in this ceremony in order to prevent these burns. PMID- 26550533 TI - Intraoral chemical burn in an elderly patient with dementia. AB - We describe the case of a 77 year-old Japanese woman who was referred to the Department of Oral and Maxillofacial Surgery at Tokyo Women's Medical University Hospital with symptoms of spontaneous intraoral pain and dysphagia evoked by accidental alkaline (calcium oxide) ingestion. The stomach and esophagus were examined under endoscopy, but no evidence of burns or ulceration associated with the calcium oxide was apparent in the upper gastrointestinal tract. Oral care, antibacterial therapy (cefmetazole sodium) and nutritional management were performed after hospitalization. Mucosal erosions, dysphagia and pneumonia were almost resolved after 16 days of oral care and antibacterial treatment. Re-burn of the oral mucosa associated with accidental ingestion was not reported after discharge. Oral management may have potential to improve the management of intraoral chemical burns, but symptomatic treatment remains the only strategy for burn management. Accidental ingestion of chemicals by patients with impaired cognition may result in dire consequences and prevention is thus more important than burn management. PMID- 26550534 TI - Transfer between an Algerian and a French hospital of four multi-drug resistant bacterial strains together via a single patient. AB - A 5 years-old girl, seriously burnt with fire, was first hospitalized during four days in an hospital at Alger, and then transferred to our hospital at Paris. Admitted in our intensive care burns unit, she was third degree burnt on 78% of total body surface area, already treated with imipenem and vancomycin at her arrival. Clinical aggravation was rapidly observed and death occurred within 24 hours. Cultures of blood and multiple wound swabs yielded 3 multi-drug resistant bacterial strains: Acinetobacter baumannii with carbapenemase OXA-23, Pseudomonas aeruginosa serotype O11 with metallo-beta-lactamase VIM-4 and Klebsiella pneumoniae with CTX-M-15 extended-spectrum beta-lactamase. Culture of a rectal swab showed colonization by Enterococcus faecium with vanA glycopeptides resistance. Patients colonized with one or two multi-drug-resistant strains were not rare in our burns unit, especially those transferred from Algeria, but this case of a single patient harboring four multi-drug-resistant strains is exceptional. PMID- 26550535 TI - PET studies in epilepsy. AB - Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. (18)Fluoro-2-deoxyglucose ((18)F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5 HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that (11)C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous sclerosis complex. (15)O-H2O PET was reported to have a similar sensitivity to FDG-PET in detecting epileptic foci. PMID- 26550536 TI - Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET: a comprehensive review of pre-clinical studies. AB - Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy 3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can be visualized and quantified non invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to the applied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether (18)F-FDG and/or (18)F-FLT PET can be used for prediction of treatment response has been analyzed in many studies both following treatment with conventional chemotherapeutic agents but also following treatment with different targeted therapies, e.g. monoclonal antibodies and small molecules inhibitors. The results from these studies have been most variable; in some studies early changes in (18)F-FDG and (18)F-FLT uptake predicted later tumor regression whereas in other studies no change in tracer uptake was observed despite the treatment being effective. The present review gives an overview of pre-clinical studies that have used (18)F-FDG and/or (18)F-FLT PET for response monitoring of cancer therapeutics. PMID- 26550537 TI - Quantitative myocardial blood flow with Rubidium-82 PET: a clinical perspective. AB - Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1) identification of the extent of a multivessel coronary artery disease (CAD) burden, 2) patients with balanced 3 vessel CAD, 3) patients with subclinical CAD, and 4) patients with regional flow variance, despite of a high global MFR. A more accurate assessment of the ischemic burden in patients with intermediate pretest probability of CAD can support the clinical decision-making in treatment of CAD patients as a complementary tool to the invasive coronary angiography (CAG). Recently, several studies have proven Rubidium-82 ((82)Rb) PET's long-term prognostic value by a significant association between compromised global MFR and major adverse cardiovascular events (MACE), and together with new diagnostic possibilities from measuring the longitudinal myocardial perfusion gradient, cardiac (82)Rb PET faces a promising clinical future. This article reviews current evidence on quantitative (82)Rb PET's ability to diagnose and risk stratify CAD patients, while assessing the potential of the modality in clinical practice. PMID- 26550538 TI - Comparison of (18)F-FDG PET/CT and PET/MRI in patients with multiple myeloma. AB - PET/MRI represents a promising hybrid imaging modality with several potential clinical applications. Although PET/MRI seems highly attractive in the diagnostic approach of multiple myeloma (MM), its role has not yet been evaluated. The aims of this prospective study are to evaluate the feasibility of (18)F-FDG PET/MRI in detection of MM lesions, and to investigate the reproducibility of bone marrow lesions detection and quantitative data of (18)F-FDG uptake between the functional (PET) component of PET/CT and PET/MRI in MM patients. The study includes 30 MM patients. All patients initially underwent (18)F-FDG PET/CT (60 min p.i.), followed by PET/MRI (120 min p.i.). PET/CT and PET/MRI data were assessed and compared based on qualitative (lesion detection) and quantitative (SUV) evaluation. The hybrid PET/MRI system provided good image quality in all cases without artefacts. PET/MRI identified 65 of the 69 lesions, which were detectable with PET/CT (94.2%). Quantitative PET evaluations showed the following mean values in MM lesions: SUVaverage=5.5 and SUVmax=7.9 for PET/CT; SUVaverage=3.9 and SUVmax=5.8 for PET/MRI. Both SUVaverage and SUVmax were significantly higher on PET/CT than on PET/MRI. Spearman correlation analysis demonstrated a strong correlation between both lesional SUVaverage (r=0.744) and lesional SUVmax (r=0.855) values derived from PET/CT and PET/MRI. Regarding detection of myeloma skeletal lesions, PET/MRI exhibited equivalent performance to PET/CT. In terms of tracer uptake quantitation, a significant correlation between the two techniques was demonstrated, despite the statistically significant differences in lesional SUVs between PET/CT and PET/MRI. PMID- 26550539 TI - Application of (18)F-FDG PET and diffusion weighted imaging (DWI) in multiple myeloma: comparison of functional imaging modalities. AB - Aim of this prospective study was to assess the sensitivity of positron emission tomography (PET) and diffusion-weighted imaging (DWI) in detecting multiple myeloma (MM) lesions, using the well-established morphologic modalities magnetic resonance imaging (MRI) and computed tomography (CT) as the standard of reference (RS). The study included 24 MM patients (15 newly diagnosed, 9 pre-treated). All underwent (18)F-FDG PET/CT and wholebody DWI. The findings in PET and DWI were compared to matching imaging findings in combined non-enhanced T1w, fat-saturated T2w (TIRM)- MRI, and low-dose CT. Patient-based analysis revealed that 15/24 patients (10 primary MM, 5 pre-treated) had myeloma lesions according to our RS. PET was positive in 13/24 patients (11 primary MM, 2 pre-treated) and DWI in 18/24 patients (12 primary MM, 6 pre-treated). Lesion-based analysis demonstrated 128 MM lesions, of which PET depicted 60/128 lesions (sensitivity 47%), while DWI depicted 99/128 lesions (sensitivity 77%). Further analysis including only the 15 untreated MM patients revealed a sensitivity of 90% for both PET and DWI and an overall concordance of PET and DWI of 72%. In conclusion, DWI was more sensitive than (18)F-FDG PET in detecting myeloma lesions in a mixed population of primary and pre-treated MM patients. However, (18)F-FDG PET and DWI demonstrated equivalent sensitivities in the sub-population of primary, untreated MM patients. This higher sensitivity of DWI in pre-treated patients may be due to the fact that (18)F-FDG PET becomes negative earlier in the course of treatment in contrary to MRI, in which already treated lesions can remain visible. PMID- 26550540 TI - Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts. AB - Bavituximab is a chimeric monoclonal antibody with immune modulating and tumor associated vascular disrupting properties demonstrated in models of non-small cell lung cancer (NSCLC). The molecular target of Bavituximab, phosphatidylserine (PS), is exposed on the outer leaflet of the membrane bi-layer of malignant vascular endothelial cells and tumor cells to a greater extent than on normal tissues. We evaluated the tumor-targeting properties of Bavituximab for imaging of NSCLC xenografts when radiolabeled with (111)In through conjugation with a bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). In vitro binding of (111)In-DOTA-Bavituximab to PS was determined by enzyme-linked immunosorbent assay (ELISA). Biodistribution of (111)In-DOTA Bavituximab was conducted in normal rats, which provided data for dosimetry calculation. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed in athymic nude rats bearing A549 NSCLC xenografts. At the molar conjugation ratio of 0.54 DOTA per Bavituximab, the PS binding affinity of (111)In-DOTA-Bavituximab was comparable to that of unmodified Bavituximab. Based on the quantitative SPECT/CT imaging data analysis, (111)In DOTA-Bavituximab demonstrated tumor-specific uptake as measured by the tumor tomuscle ratio, which peaked at 5.2 at 72 hr post-injection. In contrast, the control antibody only presented a contrast of 1.2 at the same time point.These findings may underlie the diagnostic efficacy and relative low rates of systemic vascular and immune-related toxicities of this immunoconjugate. Future applications of (111)In-DOTA-bavituximab may include prediction of efficacy, indication of tumor immunologic status, or characterization of radiographic findings. PMID- 26550541 TI - Quantitative differences in [(18)F] NaF PET/CT: TOF versus non-TOF measurements. AB - [(18)F] sodium fluoride (NaF) PET/CT is a current, clinically relevant method to assess bone metastases. Time-of-flight (TOF) PET provides better statistical data quality, which can improve either lower image noise or improve resolution, or both, depending on the image reconstruction. Improved resolution can improve quantitative measurements of standardized uptake value (SUV) in small structures. These quantitative differences may be important in both clinical interpretation and multicenter clinical trials where quantification is integral to assessing response to therapy. The purpose of this study is to determine if and by how much SUV quantitatively differs between TOF and conventional non-TOF reconstructions in [(18)F] NaF PET/CT. SUV measurements (mean and maximum) were compared in TOF and non-TOF [(18)F] NaF PET-CT reconstructions for 47 prostate cancer patients in normal regions including: soft tissue (n=282 total regions; liver, aorta, posterior abdominal fat, bladder, brain, and paraspinal muscles), and osseous structures (n=188; T12 vertebral body, femoral diaphyseal cortex, femoral head, and lateral rib). Comparisons were also made for benign degenerative changes (n=281) and metastases (n=159). TOF and non-TOF SUVs were assessed with paired t test and linear correlations. Normal soft tissue showed lower SUVmean for TOF compared to non-TOF in liver, brain, and adipose. All osseous structures showed higher SUVmean for TOF compared to non-TOF including normal regions, degenerative joint disease, and metastases. For all metastatic lesions, the average SUVmean increased by 2.5%, and in degenerative joint disease it increased by 3.5% on TOF reconstructions. Smaller lesion size was a significant factor influencing this increase in SUVmean. TOF SUVmean values are higher in osseous structures and lower in background soft tissue structures. While these differences are statistically significant, the magnitudes of these changes are relatively modest. Smaller osseous lesions may have higher contrast and higher SUVmean values with TOF reconstruction compared to non-TOF reconstructions. The differences in TOF vs. non-TOF images should be considered when evaluating response to therapy and in the design of multi-center clinical trials. PMID- 26550542 TI - Separation of beta-amyloid binding and white matter uptake of (18)F-flutemetamol using spectral analysis. AB - The kinetic components of the beta-amyloid ligand (18)F-flutemetamol binding in grey and white matter were investigated through spectral analysis, and a method developed for creation of parametric images separating grey and white matter uptake. Tracer uptake in grey and white matter and cerebellar cortex was analyzed through spectral analysis in six subjects, with (n=4) or without (n=2) apparent beta-amyloid deposition, having undergone dynamic (18)F-flutemetamol scanning with arterial blood sampling. The spectra were divided into three components: slow, intermediate and fast basis function rates. The contribution of each of the components to total volume of distribution (VT) was assessed for different tissue types. The slow component dominated in white matter (average 90%), had a higher contribution to grey matter VT in subjects with beta-amyloid deposition (average 44%) than without (average 6%) and was absent in cerebellar cortex, attributing the slow component of (18)F-flutemetamol uptake in grey matter to beta-amyloid binding. Parametric images of voxel-based spectral analysis were created for VT, the slow component and images segmented based on the slow component contribution; confirming that grey matter and white matter uptake can be discriminated on voxel level using a threshold for the contribution from the slow component to VT. PMID- 26550543 TI - Dosage optimization in positron emission tomography: state-of-the-art methods and future prospects. AB - Positron emission tomography (PET) is widely used nowadays for tumor staging and therapy response in the clinic. However, average PET radiation exposure has increased due to higher PET utilization. This study aims to review state-of-the art PET tracer dosage optimization methods after accounting for the effects of human body attenuation and scan protocol parameters on the counting rate. In particular, the relationship between the noise equivalent count rate (NECR) and the dosage (NECR-dosage curve) for a range of clinical PET systems and body attenuation sizes will be systematically studied to prospectively estimate the minimum dosage required for sufficiently high NECR. The optimization criterion can be determined either as a function of the peak of the NECR-dosage curve or as a fixed NECR score when NECR uniformity across a patient population is important. In addition, the systematic NECR assessments within a controllable environment of realistic simulations and phantom experiments can lead to a NECR-dosage response model, capable of predicting the optimal dosage for every individual PET scan. Unlike conventional guidelines suggesting considerably large dosage levels for obese patients, NECR-based optimization recommends: i) moderate dosage to achieve 90% of peak NECR for obese patients, ii) considerable dosage reduction for slimmer patients such that uniform NECR is attained across the patient population, and iii) prolongation of scans for PET/MR protocols, where longer PET acquisitions are affordable due to lengthy MR sequences, with motion compensation becoming important then. Finally, the need for continuous adaptation of dosage optimization to emerging technologies will be discussed. PMID- 26550545 TI - Ergonomic Assessment of Floor-based and Overhead Lifts. AB - Manual full-body vertical lifts of patients have high risk for developing musculoskeletal disorders. Two primary types of battery-powered lift assist devices are available for these tasks: floor-based and overhead-mounted devices. Studies suggest that the operation of floor-based devices may require excessive pushing and pulling forces and that overhead-mounted devices are safer and require lower operating forces. This study evaluated required operating hand forces and resulting biomechanical spinal loading for overhead-mounted lifts versus floor-based lifts across various floor surfaces and patient weight conditions. We did not examine differences in how operators performed the tasks, but rather focused on differences in required operating forces and estimated biomechanical loads across various exposure conditions for a typical operator. Findings show that the floor-based lifts exceeded recommended exposure limits for pushing and pulling for many of the floor/weight conditions and that the overhead mounted lifts did not. As expected, forces and spinal loads were greater for nonlinoleum floor surfaces compared with linoleum floors. Based on these findings, it is suggested that overhead-mounted devices be used whenever possible, particularly in instances where carpeted floors would be encountered. PMID- 26550544 TI - The use of dynamic nuclear polarization (13)C-pyruvate MRS in cancer. AB - In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is (13)C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized (13)C-pyruvate results in appearance of (13)C-lactate, (13)C-alanine and (13)C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced (13)C pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized (13)C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated (13)C lactate/(13)C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized (13)C MRS imaging of cancer. PMID- 26550546 TI - Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection. AB - Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Naive (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-gamma producing T cells were markedly decreased. Although CD14(high)CD16- proinflammatory monocytes were modestly increased, IFN gammaR+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD CD38+CD27(lo)) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. PMID- 26550547 TI - Treatment of Diabetes and/or Hypertension Using Medicinal Plants in Cameroon. AB - Medicinal plants have served as valuable starting materials for drug development in both developing and developed countries. Today, more than 80% of the people living in Africa were depended on medicinal plants based medicines to satisfy their healthcare needs. The main goal of the present study was to collect and document information on herbal remedies traditionally used for the treatment of diabetes and/or hypertension in Cameroon. To reach this objective, data were collected from 328 patients who have been diagnosed at least once by a physician as diabetics and/or hypertension patients. One hundred and eighty two (182) among them took for a period of 10 days different varieties of medicinal plants which were prepared in form of decoction, maceration and infusion and administered orally twice or three times daily. As result, 70% of patients who used plants were relieved at the end of the treatment. Thirty-three plants have been recorded and documented for the treatment of diabetes and/or hypertension. The results of this study can stimulate a sustainable development by providing the basis for drugs discovery and by documenting biodiversity for long time exploitation. PMID- 26550548 TI - Use of Traditional Botanical Medicines During Pregnancy in Rural Rwanda. AB - OBJECTIVE: To evaluate the perceptions of healthcare and traditional medicine providers regarding the type, indications, side effects, and prevalence of traditional medicine use amongst pregnant women in a rural Rwandan population. METHODS: Six focus groups with physicians, nurses, and community health workers and four individual in-depth interviews with traditional medicine providers were held. Qualitative data was gathered using a structured questionnaire querying perceptions of the type, indications, side effects, and prevalence of use of traditional medicines in pregnancy. RESULTS: The healthcare provider groups perceived a high prevalence of traditional botanical medicine use by pregnant women (50-80%). All three groups reported similar indications for use of the medicines and the socioeconomic status of the pregnant women who use them. The traditional medicine providers and the healthcare providers both perceived that the most commonly used medicine is a mixture of many plants, called Inkuri. The most serious side effect reported was abnormally bright green meconium with a poor neonatal respiratory drive. Thirty-five traditional medicines were identified that are used during pregnancy. CONCLUSION: Perceptions of high prevalence of use of traditional medicines during pregnancy with possible negative perinatal outcomes exist in areas of rural Rwanda. PMID- 26550549 TI - Pseudoaddiction: Fact or Fiction? An Investigation of the Medical Literature. AB - Tremendous growth in opioid prescribing over two decades in the USA has correlated with proportional increases in diversion, addiction, and overdose deaths. Pseudoaddiction, a concept coined in 1989, has frequently been cited to indicate that under-treatment of pain, rather than addiction, is the more pressing and authentic clinical problem in opioid-seeking patients. This investigative review searched Medline articles containing the term "pseudoaddiction" to determine its footprint in the literature with a focus on how it has been characterized and empirically validated. By 2014, pseudoaddiction was discussed in 224 articles. Only 18 of these articles contributed to or questioned pseudoaddiction from an anecdotal or theoretical standpoint, and none empirically tested or confirmed its existence. Twelve of these articles, including all four that acknowledged pharmaceutical funding, were proponents of pseudoaddiction. These papers described pseudoaddiction as an iatrogenic disease resulting from withholding opioids for pain that can be diagnosed, prevented, and treated with more aggressive opioid treatment. In contrast, six articles, none with pharmaceutical support, questioned pseudoaddiction as a clinical construct. Empirical evidence supporting pseudoaddiction as a diagnosis distinct from addiction has not emerged. Nevertheless, the term has been accepted and proliferated in the literature as a justification for opioid therapy for non terminal pain in patients who may appear to be addicted but should not, from the perspective of pseudoaddiction, be diagnosed with addiction. Future studies should examine whether acceptance of pseudoaddiction has complicated accurate pain assessment and treatment, and whether it has contributed to or reflected medical-cultural shifts that produced the iatrogenic opioid addiction epidemic. PMID- 26550550 TI - Exploring the Relationship Between Childhood Maltreatment and Addiction: A Review of the Neurocognitive Evidence. AB - Childhood maltreatment has been shown to increase the risk of a range of psychiatric disorders including substance use disorders (SUDs) and is associated with the onset, course and severity of illness. We review the evidence for alterations in brain structure and neurocognitive processing in individuals who have experienced childhood maltreatment, focusing specifically on changes related to reward processing, executive functioning and affect processing. Changes in these neurocognitive systems have been documented in adults presenting with SUDs, who are typically characterized by heightened subcortico-striatal responses to salient stimuli and impairments in fronto-cingulate regulation. Maltreatment specific effects in these processing domains may account for the particularly severe clinical presentation of SUDs in adults with histories of maltreatment in childhood. The findings are considered in relation to the theory of latent vulnerability, which contends that alterations in these neurocognitive systems may reflect calibration to early risk environments that in turn increases the risk of developing of SUDs later in life. PMID- 26550551 TI - Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach. AB - Substance abuse and drug addiction are two of the most common psychopathologies among the general population. While a host of risk factors are associated with the onset of drug abuse and drug addiction, there is a growing body of evidence pointing to the powerful influence of early adverse experiences, both child neglect and maltreatment, as well as drug use and abuse in parents and/or primary caretakers. We consider the case for drug addiction as a developmental disorder, outlining the need to consider the role of genetic, epigenetic, and neurobiological factors alongside experiences of adversity at key stages of development. Such a multilevel approach within a developmental framework has the potential to reframe our understanding of how addiction emerges and is maintained, and is essential if we are to identify the mechanisms underlying this disorder to better inform effective treatment and prevention across the generations. PMID- 26550553 TI - Cost analysis of hospitalized Clostridium difficile-associated diarrhea (CDAD). AB - AIM: Clostridium difficile-associated diarrhea (CDAD) causes heavy financial burden on healthcare systems worldwide. As with all hospital-acquired infections, prolonged hospital stays are the main cost driver. Previous cost studies only include hospital billing data and compare the length of stay in contrast to non infected patients. To date, a survey of actual cost has not yet been conducted. METHOD: A retrospective analysis of data for patients with nosocomial CDAD was carried out over a 1-year period at the University Hospital of Greifswald. Based on identification of CDAD related treatment processes, cost of hygienic measures, antibiotics and laboratory as well as revenue losses due to bed blockage and increased length of stay were calculated. RESULTS: 19 patients were included in the analysis. On average, a CDAD patient causes additional costs of ? 5,262.96. Revenue losses due to extended length of stay take the highest proportion with ? 2,555.59 per case, followed by loss in revenue due to bed blockage during isolation with ? 2,413.08 per case. Overall, these opportunity costs accounted for 94.41% of total costs. In contrast, costs for hygienic measures (? 253.98), pharmaceuticals (? 22.88) and laboratory (? 17.44) are quite low. CONCLUSION: CDAD results in significant additional costs for the hospital. This survey of actual costs confirms previous study results. PMID- 26550552 TI - Human Ascariasis: Diagnostics Update. AB - Soil-transmitted helminths (STHs) infect over one billion people worldwide. Ascariasis may mimic a number of conditions, and individual clinical diagnosis often requires a thorough work-up. Kato-Katz thick smears are the standard detection method for Ascaris and, despite low sensitivity, are often used for mapping and monitoring and evaluation of national control programmes. Although increased sampling (number of stools) and diagnostic (number of examinations per stool) efforts can improve sensitivity, Kato-Katz is less sensitive than other microscopy methods such as FLOTAC(r). Antibody-based diagnostics may be a sensitive diagnostic tool; however, their usefulness is limited to assessing transmission in areas aiming for elimination. Molecular diagnostics are highly sensitive and specific, but high costs limit their use to individual diagnosis, drug - efficacy studies and identification of Ascaris suum. Increased investments in research on Ascaris and other STHs are urgently required for the development of diagnostic assays to support efforts to reduce human suffering caused by these infections. PMID- 26550554 TI - Epidemiology and contemporary risk profile of traumatic spinal cord injury in Switzerland. AB - BACKGROUND: Traumatic spinal cord injury (TSCI) has a high personal and socio economic impact. Effective public health prevention policies that aim to reduce this burden are reliant on contemporary information of the risk and underlying causes of TSCI. This study contextualizes Swiss annual incidence rates within the European context, and provides detailed estimates by age, gender and etiology towards informing targeted intervention strategies. METHODS: TSCI cases that occurred in the years 2005 to 2012 were identified as part of the Swiss Spinal Cord Injury (SwiSCI) cohort study through a rehabilitation-based study of local medical files. RESULTS: The crude annual incidence rate (IR) estimate of TSCI for the study period was 18.0 (95 % confidence interval 16.9-19.2) per one million population; standardized to the WHO world population IR was 21.7 (20.3-23.1) population. The injury rate of TSCI in Switzerland was intermediate in comparison to estimates for other European countries, which ranged from around 8.3 in Denmark to 33.6 per million in Greece. Males exhibited consistently higher IRs than females, with a highest IR ratio (IRR) of 3.9 (2.8-5.5) in young adults (aged 16 to 30). Sports and leisure and transport-related injuries were the predominant causes of TSCI in the youngest age group (aged 16 to 30); falls were the predominant cause among the oldest age group (76 years or over). With increasing age, a greater proportion of fall-related TSCIs were due to low-level falls, with more than 80 % of fall-related TSCIs due to low-level falls in the oldest age group. CONCLUSIONS: Evidence suggests sports/leisure- and transport related injuries in young men and falls among the elderly as prime targets for prevention policies and programs. PMID- 26550555 TI - Use of geographic information systems to assess the error associated with the use of place of residence in injury research. AB - BACKGROUND: In any spatial research, the use of accurate location data is critical to the reliability of the results. Unfortunately, however, many of the administrative data sets used in injury research do not include the location at which the injury takes place. The aim of this paper is to examine the error associated with using place of residence as opposed to place of injury when identifying injury hotspots and hospital access. METHODS: Traumatic Brian Injury (TBI) data from the BC Trauma Registry (BCTR) was used to identify all TBI patients admitted to BC hospitals between January 2000 and March 2013. In order to estimate how locational error impacts the identification of injury hotspots, the data was aggregated to the level of dissemination area (DA) and census tract (CT) and a linear regression was performed using place of residence as a predictor for place of injury. In order to assess the impact of locational error in studies examining hospital access, an analysis of the driving time between place of injury and place of residence and the difference in driving time between place of residence and the treatment hospital, and place of injury and the same hospital was conducted. RESULTS: The driving time analysis indicated that 73.3 % of the injuries occurred within 5 min of place of residence, 11.2 % between five and ten minutes and 15.5 % over 20 min. Misclassification error occurs at both the DA and CT level. The residual map of the DA clearly shows more detailed misclassification. As expected, the driving time between place of residence and place of injury and the difference between these same two locations and the treatment hospital share a positive relationship. In fact, the larger the distance was between the two locations, the larger the error was when estimating access to hospital. CONCLUSIONS: Our results highlight the need for more systematic recording of place of injury as this will allow researchers to more accurately pinpoint where injuries occur. It will also allow researchers to identify the causes of these injuries and to determine how these injuries might be prevented. PMID- 26550556 TI - What determines adult cognitive skills? Influences of pre-school, school, and post-school experiences in Guatemala. AB - Most empirical investigations of the effects of cognitive skills assume that they are produced by schooling. Drawing on longitudinal data to estimate production functions for adult verbal and nonverbal cognitive skills, we find that: (1) School attainment has a significant and substantial effect on adult verbal cognitive skills but not on adult nonverbal cognitive skills; and (2) Pre-school and post-school experiences also have substantial positive significant effects on adult cognitive skills. Pre-school experiences captured by height for age at 6 years substantially and significantly increase adult nonverbal cognitive skills, even after controlling for school attainment. Post-school tenure in skilled jobs has significant positive effects on both types of cognitive skills. The findings (1) reinforce the importance of early life investments; (2) support the importance of childhood nutrition ("Flynn effect") and work complexity in explaining increases in nonverbal cognitive skills; (3) call into question interpretations of studies reporting productivity impacts of cognitive skills that do not control for endogeneity; and (4) point to limitations in using adult school attainment alone to represent human capital. PMID- 26550557 TI - A Novel Codon-optimized SIV Gag-pol Immunogen for Gene-based Vaccination. AB - Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four "self-cleaving" picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences. PMID- 26550558 TI - Long-term efficacy of vildagliptin in patients with type 2 diabetes undergoing hemodialysis. AB - BACKGROUND: There are few studies evaluating long-term glycemic control using a dipeptidyl peptidase-4 inhibitor in type 2 diabetes patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the safety and efficacy of vildagliptin therapy over 2 years in type 2 diabetes with ESRD. METHODS: Patients with ESRD resulting from type 2 diabetes requiring dialysis who had >=20 % glycated albumin (GA) were enrolled. Vildagliptin 50 mg once daily was administered for 2 years. Changes in GA and dry weight were evaluated. RESULTS: In 32 patients (24 men and 8 women) aged 68.3 +/- 1.9 years, vildagliptin 50 mg once daily was administered for 2 years, but the dose was increased to 50 mg twice daily in 15 patients. GA was significantly reduced by 2.6 +/- 0.6 %, from 22.4 +/- 0.6 % at baseline to 19.8 +/- 0.4 % at 2 years. After 2 years of vildagliptin therapy, 15 (46.9 %) of 32 patients achieved a GA level of <20 %. Dry weight changed slightly, with an increase of 1.3 +/- 0.8 kg at 2 years. No adverse drug reactions related to treatment with vildagliptin were seen. CONCLUSIONS: Vildagliptin is a promising therapeutic option for safe, effective glycemic control in type 2 diabetic patients with ESRD. PMID- 26550559 TI - Temporomandibular joint disorder from skull-base osteomyelitis: a case report. AB - Skull-base osteomyelitis is a rare disease affecting the medulla of the temporal, sphenoid, and occipital bones. In general, it occurs due to external ear canal infections caused by malignant external otitis. Skull-base osteomyelitis usually affects elderly diabetic patients. The patient, a 58-year-old man, was referred for evaluation and management of the left jaw. Clinical examination of the patient revealed pain in the left jaw and mouth-opening deflection to the left. The maximum active mouth opening was measured to about 27 mm. Panoramic, CT, and CBCT revealed bone resorption patterns in the left condyle. Through control of diabetes, continued pharmacological treatment, arthrocentesis, and occlusal stabilization appliance therapy were carried out. The extent of active mouth opening was increased to 45 mm, and pain in the left jaw joint was alleviated. This was a case wherein complications caused by failure to control diabetes induced skull-base osteomyelitis. There is a need for continued discussion about the advantages and disadvantages of arthrocentesis with lavage for patients with skull-base osteomyelitis and other treatment options. PMID- 26550560 TI - Facelift incision and superficial musculoaponeurotic system advancement in parotidectomy: case reports. AB - Surgical procedures for parotidectomy had been developed to gain adequate approach, prevent morbidity of nerve, and give esthetic satisfaction. We performed two cases of parotidectomy through facelift incision. One case was reconstructed with superficial musculoaponeurotic system (SMAS) flap and sternocleidomastoid (SCM) muscle rotated flap at the parotid bed. In second case, same procedures were performed, but collagen membrane was additionally implanted for prevention of Frey's syndrome. After surgery, two cases showed esthetic results without neck scar and hollow defect on parotid bed area. PMID- 26550562 TI - Molecular identification and susceptibility of clinically relevant Scedosporium spp. in China. AB - As various new sibling species within the Scedosporium spp. have been described recently, this study was conducted to investigate distribution and antifungal susceptibility profiles of the different species of Scedosporium spp. in China. Twenty-one clinical strains of Scedosporium from China and two strains from Japan were reidentified by MLSA. The analysis included BT2, CAL, RPB, SOD, and ACT and the combination of the five loci. Pseudallescheria boydii complex (17 strains) and S. apiospermum (6 strains) were identified. P. boydii complex included four closely related subgroups: P. boydii (9 strains), P. ellipsoidea (6 strains), P. fusoidea (1 strain), and P. angusta (1 strain). There were no significant differences in MICs for neither VOR, POS, nor AMB over all the five species in study. For itraconazole, intraspecific diversity was evident. PMID- 26550561 TI - Evidence of Mitochondrial Dysfunction within the Complex Genetic Etiology of Schizophrenia. AB - Genetic evidence has supported the hypothesis that schizophrenia (SZ) is a polygenic disorder caused by the disruption in function of several or many genes. The most common and reproducible cellular phenotype associated with SZ is a reduction in dendritic spines within the neocortex, suggesting alterations in dendritic architecture may cause aberrant cortical circuitry and SZ symptoms. Here, we review evidence supporting a multifactorial model of mitochondrial dysfunction in SZ etiology and discuss how these multiple paths to mitochondrial dysfunction may contribute to dendritic spine loss and/or underdevelopment in some SZ subjects. The pathophysiological role of mitochondrial dysfunction in SZ is based upon genomic analyses of both the mitochondrial genome and nuclear genes involved in mitochondrial function. Previous studies and preliminary data suggest SZ is associated with specific alleles and haplogroups of the mitochondrial genome, and also correlates with a reduction in mitochondrial copy number and an increase in synonymous and nonsynonymous substitutions of mitochondrial DNA. Mitochondrial dysfunction has also been widely implicated in SZ by genome-wide association, exome sequencing, altered gene expression, proteomics, microscopy analyses, and induced pluripotent stem cell studies. Together, these data support the hypothesis that SZ is a polygenic disorder with an enrichment of mitochondrial targets. PMID- 26550563 TI - Immunohistochemical expression of ornithine decarboxylase, diamine oxidase, putrescine, and spermine in normal canine enterocolic mucosa, in chronic colitis, and in colorectal cancer. AB - We compared the immunohistochemical expression of putrescine (PUT), spermine (SPM), ornithine decarboxylase (ODC), and diamine oxidase (DAO) in bioptic samples of canine colonic mucosa with chronic inflammation (i.e., granulomatous colitis and lymphoplasmacytic colitis) or neoplasia. Single and total polyamines levels were significantly higher in neoplastic tissue than in normal samples. Samples with different degrees of inflammation showed a general decrease expression of ODC if compared to controls; SPM was practically not expressed in control samples and very low in samples with chronic-granulomatous inflammation. In carcinomatous samples, the ODC activity was higher with respect to controls and samples with inflammation. This is the first description of polyamines expression in dog colonic mucosa in normal and in different pathological conditions, suggesting that the balance between polyamine degradation and biosynthesis is evidently disengaged during neoplasia. PMID- 26550564 TI - The level of circulating endothelial progenitor cell is associated with cerebral vasoreactivity: a pilot study. AB - Endothelial progenitor cell is known to be able to repair injured vessels. We assessed the hypothesis that endothelial progenitor cell also modulates cerebral endothelial function in healthy status. We used transcranial color-coded sonography to measure middle cerebral arterial vasoreactivity to CO2 (breath holding index) in healthy subjects and observed its relationship with the number of circulating CD34CD133+ cells. To detect significant correlations between each characteristic and breath-holding index of middle cerebral artery, we used univariate and multivariate regression analyses. 22 young healthy subjects were included in the present study (6 men, 16 women; mean age: 28.45 +/- 3.98 years, range: 22-34 years). The mean breath-holding index and CD45(low)CD34+CD133+ cells number were 0.95 +/- 0.48% and 0.52 +/- 0.26, respectively. The level of CD34CD133+ cells was independently associated with middle cerebral artery's vasoreactivity (r = 0.439, P = 0.04). Our results suggest that endothelial progenitor cell also modulates healthy cerebral vessels' endothelial function. This ability of endothelial progenitor cell could be potentially applied therapeutically and for prevention in conditions with cerebral endothelial dysfunction and cerebral ischemia. PMID- 26550565 TI - Bone regeneration by nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) scaffolds seeded with human umbilical cord mesenchymal stem cells in the calvarial defects of the nude mice. AB - In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro and subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n = 18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p < 0.01). On the basis of previous studies in vitro and in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage. PMID- 26550566 TI - Production of monoclonal antibodies in plants for cancer immunotherapy. AB - Plants are considered as an alternative platform for recombinant monoclonal antibody (mAb) production due to the improvement and diversification of transgenic techniques. The diversity of plant species offers a multitude of possibilities for the valorization of genetic resources. Moreover, plants can be propagated indefinitely, providing cheap biomass production on a large scale in controlled conditions. Thus, recent studies have shown the successful development of plant systems for the production of mAbs for cancer immunotherapy. However, their several limitations have to be resolved for efficient antibody production in plants. PMID- 26550567 TI - Current and new approaches in GMO detection: challenges and solutions. AB - In many countries, genetically modified organisms (GMO) legislations have been established in order to guarantee the traceability of food/feed products on the market and to protect the consumer freedom of choice. Therefore, several GMO detection strategies, mainly based on DNA, have been developed to implement these legislations. Due to its numerous advantages, the quantitative PCR (qPCR) is the method of choice for the enforcement laboratories in GMO routine analysis. However, given the increasing number and diversity of GMO developed and put on the market around the world, some technical hurdles could be encountered with the qPCR technology, mainly owing to its inherent properties. To address these challenges, alternative GMO detection methods have been developed, allowing faster detections of single GM target (e.g., loop-mediated isothermal amplification), simultaneous detections of multiple GM targets (e.g., PCR capillary gel electrophoresis, microarray, and Luminex), more accurate quantification of GM targets (e.g., digital PCR), or characterization of partially known (e.g., DNA walking and Next Generation Sequencing (NGS)) or unknown (e.g., NGS) GMO. The benefits and drawbacks of these methods are discussed in this review. PMID- 26550568 TI - Regulation of synthesis and roles of hyaluronan in peritoneal dialysis. AB - Hyaluronan (HA) is a ubiquitous extracellular matrix glycosaminoglycan composed of repeated disaccharide units of alternating D-glucuronic acid and D-N acetylglucosamine residues linked via alternating beta-1,4 and beta-1,3 glycosidic bonds. HA is synthesized in humans by HA synthase (HAS) enzymes 1, 2, and 3, which are encoded by the corresponding HAS genes. Previous in vitro studies have shown characteristic changes in HAS expression and increased HA synthesis in response to wounding and proinflammatory cytokines in human peritoneal mesothelial cells. In addition, in vivo models and human peritoneal biopsy samples have provided evidence of changes in HA metabolism in the fibrosis that at present accompanies peritoneal dialysis treatment. This review discusses these published observations and how they might contribute to improvement in peritoneal dialysis. PMID- 26550569 TI - ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment. AB - TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment. PMID- 26550570 TI - An electromechanical left ventricular wedge model to study the effects of deformation on repolarization during heart failure. AB - Heart failure is a major and costly problem in public health, which, in certain cases, may lead to death. The failing heart undergo a series of electrical and structural changes that provide the underlying basis for disturbances like arrhythmias. Computer models of coupled electrical and mechanical activities of the heart can be used to advance our understanding of the complex feedback mechanisms involved. In this context, there is a lack of studies that consider heart failure remodeling using strongly coupled electromechanics. We present a strongly coupled electromechanical model to study the effects of deformation on a human left ventricle wedge considering normal and hypertrophic heart failure conditions. We demonstrate through a series of simulations that when a strongly coupled electromechanical model is used, deformation results in the thickening of the ventricular wall that in turn increases transmural dispersion of repolarization. These effects were analyzed in both normal and failing heart conditions. We also present transmural electrograms obtained from these simulations. Our results suggest that the waveform of electrograms, particularly the T-wave, is influenced by cardiac contraction on both normal and pathological conditions. PMID- 26550571 TI - Building integrated ontological knowledge structures with efficient approximation algorithms. AB - The integration of ontologies builds knowledge structures which brings new understanding on existing terminologies and their associations. With the steady increase in the number of ontologies, automatic integration of ontologies is preferable over manual solutions in many applications. However, available works on ontology integration are largely heuristic without guarantees on the quality of the integration results. In this work, we focus on the integration of ontologies with hierarchical structures. We identified optimal structures in this problem and proposed optimal and efficient approximation algorithms for integrating a pair of ontologies. Furthermore, we extend the basic problem to address the integration of a large number of ontologies, and correspondingly we proposed an efficient approximation algorithm for integrating multiple ontologies. The empirical study on both real ontologies and synthetic data demonstrates the effectiveness of our proposed approaches. In addition, the results of integration between gene ontology and National Drug File Reference Terminology suggest that our method provides a novel way to perform association studies between biomedical terms. PMID- 26550572 TI - Actions of probiotics on trinitrobenzenesulfonic acid-induced colitis in rats. AB - We investigated the actions of probiotics, Streptococcus faecalis 129 BIO 3B (SF3B), in a trinitrobenzenesulfonic acid- (TNBS-) induced colitis model in rats. After TNBS was administered into the colons of rats for induction of colitis, the rats were divided into two groups: one group was given a control diet and the other group was given a diet containing SF3B for 14 days. There were no apparent differences in body weight, diarrhea period, macroscopic colitis score, and colonic weight/length ratio between the control group and SF3B group, suggesting that induction of colitis was not prevented by SF3B. Next, we investigated whether SF3B-containing diet intake affects the restoration of enteric neurotransmissions being damaged during induction of colitis by TNBS using isolated colonic preparations. Recovery of the nitrergic component was greater in the SF3B group than in the control group. A compensatory appearance of nontachykininergic and noncholinergic excitatory components was less in the SF3B group than in the control group. In conclusion, the present study suggests that SF3B-containing diet intake can partially prevent disruptions of enteric neurotransmissions induced after onset of TNBS-induced colitis, suggesting that SF3B has therapeutic potential. PMID- 26550573 TI - Smooth muscle cells of penis in the rat: noninvasive quantification with shear wave elastography. AB - PURPOSE: Smooth muscle cells (SMCs) of cavernosum play an important role in erection. It is of great significance to quantitatively analyze the level of SMCs in penis. In this study, we investigated the feasibility of shear wave elastography (SWE) on evaluating the level of SMCs in penis quantitatively. MATERIALS AND METHODS: Twenty healthy male rats were selected. The SWE imaging of penis was carried out and then immunohistochemistry analysis of penis was performed to analyze the expression of alpha smooth muscle actin in penis. The measurement index of SWE examination was tissue stiffness (TS). The measurement index of immunohistochemistry analysis was positive area percentage of alpha smooth muscle actin (AP). RESULTS: Sixty sets of data of TS and AP were obtained. The results showed that TS was significantly correlated with AP and the correlation coefficient was -0.618 (p < 0.001). The result of TS had been plotted against the AP measurements. The relation between the two results has been fitted with quadric curve; the goodness-of-fit index was 0.364 (p < 0.001). CONCLUSIONS: The level of SMCs in penis was successfully quantified in vivo with SWE. SWE can be used clinically for evaluating the level of SMCs in penis quantitatively. PMID- 26550574 TI - The diagnosis value of promoter methylation of UCHL1 in the serum for progression of gastric cancer. AB - BACKGROUND: Aberrant promoter methylation has been considered as a potential molecular marker for gastric cancer (GC). However, the role of methylation of FLNC, THBS1, and UCHL1 in the development and progression of GC has not been explored. METHODS: The promoter methylation status of UCHL1, FLNC, THBS1, and DLEC1 was assessed by quantitative methylation-specific PCR (QMSP) in the serum of 82 GC patients, 46 chronic atrophic gastritis (CAG) subjects, and 40 healthy controls. RESULTS: All four genes had significantly higher methylation levels in GC patients than in CAG and control subjects. However, only UCHL1 methylation was significantly correlated with the tumor stage and lymph node metastasis. While THBS1 methylation was altered in an age-dependent manner, FLNC methylation was correlated with differentiation and Helicobacter pylori infection. DLEC1 methylation was only associated with tumor size. Moreover, methylated UCHL1 with or without THBS1 in the serum was found to be significantly associated with a poor prognosis. CONCLUSION: The promoter methylation degree of FLNC, THBS1, UCHL1, and DLEC1 in serum could tell the existence of GC and only UCHL1 in the serum was also associated with poor prognosis of GC. PMID- 26550575 TI - Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention. PMID- 26550576 TI - Ras oncogene-mediated progressive silencing of extracellular superoxide dismutase in tumorigenesis. AB - Extracellular superoxide dismutase (SOD3) is a secreted enzyme that uses superoxide anion as a substrate in a dismutase reaction that results in the formation of hydrogen peroxide. Both of these reactive oxygen species affect growth signaling in cells. Although SOD3 has growth-supporting characteristics, the expression of SOD3 is downregulated in epithelial cancer cells. In the current work, we studied the mechanisms regulating SOD3 expression in vitro using thyroid cell models representing different stages of thyroid cancer. We demonstrate that a low level of RAS activation increases SOD3 mRNA synthesis that then gradually decreases with increasing levels of RAS activation and the decreasing degree of differentiation of the cancer cells. Our data indicate that SOD3 regulation can be divided into two classes. The first class involves RAS driven reversible regulation of SOD3 expression that can be mediated by the following mechanisms: RAS GTPase regulatory genes that are responsible for SOD3 self-regulation; RAS-stimulated p38 MAPK activation; and RAS-activated increased expression of the mir21 microRNA, which inversely correlates with sod3 mRNA expression. The second class involves permanent silencing of SOD3 mediated by epigenetic DNA methylation in cells that represent more advanced cancers. Therefore, the work suggests that SOD3 belongs to the group of ras oncogene silenced genes. PMID- 26550577 TI - Glutamine may repress the weak LPS and enhance the strong heat shock induction of monocyte and lymphocyte HSP72 proteins but may not modulate the HSP72 mRNA in patients with sepsis or trauma. AB - OBJECTIVE: We assessed the lipopolysaccharide (LPS) or heat shock (HS) induction of heat shock protein-72 (HSP72) in peripheral blood mononuclear cells (PBMCs) of patients with severe sepsis (SS) or trauma-related systemic inflammatory response syndrome (SIRS), compared to healthy individuals (H); we also investigated any pre- or posttreatment modulating glutamine (Gln) effect. METHODS: SS (11), SIRS (10), and H (19) PBMCs were incubated with 1 MUg/mL LPS or 43 degrees HS. Gln 10 mM was either added 1 h before or 1 h after induction or was not added at all. We measured monocyte (m), lymphocyte (l), mRNA HSP72, HSP72 polymorphisms, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and cortisol levels. RESULTS: Baseline lHSP72 was higher in SS (p < 0.03), and mHSP72 in SIRS (p < 0.02), compared to H. Only HS induced l/mHSP72/mRNA HSP72; LPS induced IL-6, IL-8, IL-10, and MCP-1. Induced mRNA was related to l/mHSP72, and was related negatively to cytokines. Intracellular l/mHSP72/HSP72 mRNA was related to serum ILs, not being influenced by cortisol, illness severity, and HSP72 polymorphisms. Gln did not induce mRNA in any group but modified l/mHSP72 after LPS/HS induction unpredictably. CONCLUSIONS: HSP72 mRNA and l/mHSP72 are higher among critically ill patients, further induced by HS, not by LPS. HSP72 proteins and HSP72 mRNA are related to serum ILs and are negatively related to supernatant cytokines, not being influenced by HSP72 polymorphisms, cortisol, or illness severity. Gln may depress l/mHSP72 after LPS exposure and enhance them after HS induction, but it may not affect early induced HSP72 mRNA. PMID- 26550579 TI - Ocular surgical models for immune and angiogenic responses. AB - Corneal transplantation serves as a reproducible and simple surgical model to study mechanisms regulating immunity and angiogenesis. The simplicity of the model allows for systematic analysis of different mechanisms involved in immune and angiogenic privilege and their failures. This protocol describes how to induce neovessels and inflammation in an actively regulated avascular and immune privileged site. This involves placing intra-stromal corneal sutures for two weeks, disrupting the privileges, and performing corneal transplantation subsequently. Privileged and non-privileged recipient responses to donor cornea can be compared to identify key immunological mechanisms that underlie angiogenesis and graft rejection. This protocol can also be adapted to the growing repertoire of genetic models available in the mouse, and is a valuable tool to elucidate molecular mechanisms mediating acceptance or failure of corneal graft. The model could be used to assess the potential of therapeutic molecules to enhance graft survival in vivo. PMID- 26550578 TI - Contribution of Genetic Factors to Sjogren's Syndrome and Sjogren's Syndrome Related Lymphomagenesis. AB - We aimed to summarize the current evidence related to the contributory role of genetic factors in the pathogenesis of Sjogren's syndrome (SS) and SS-related lymphoma. Genes within the major histocompatibility complex (MHC) locus previously considered conferring increased susceptibility to SS development have been also revealed as important contributors in recent genome wide association studies. Moreover, genetic variations outside the MHC locus involving genes in type I interferon pathway, NF-kappaB signaling, B- and T-cell function and methylation processes have been shown to be associated with both SS and SS related lymphoma development. Appreciating the functional implications of SS related genetic variants could provide further insights into our understanding of SS heterogeneity, allowing the design of tailored therapeutic interventions. PMID- 26550581 TI - Examination of the Blood Brain Barrier integrity in a mouse model of the neurodegenerative Canavan's disease. PMID- 26550580 TI - Geographic Expansion of Lyme Disease in the Southeastern United States, 2000 2014. AB - Background. The majority of Lyme disease cases in the United States are acquired on the east coast between northern Virginia and New England. In recent years the geographic extent of Lyme disease has been expanding, raising the prospect of Lyme disease becoming endemic in the southeast. Methods. We collected confirmed and probable cases of Lyme disease from 2000 through 2014 from the Virginia Department of Health and North Carolina Department of Public Health and entered them in a geographic information system. We performed spatial and spatiotemporal cluster analyses to characterize Lyme disease expansion. Results. There was a marked increase in Lyme disease cases in Virginia, particularly from 2007 onwards. Northern Virginia experienced intensification and geographic expansion of Lyme disease cases. The most notable area of expansion was to the southwest along the Appalachian Mountains with development of a new disease cluster in the southern Virginia mountain region. Conclusions. The geographic distribution of Lyme disease cases significantly expanded in Virginia between 2000 and 2014, particularly southward in the Virginia mountain ranges. If these trends continue, North Carolina can expect autochthonous Lyme disease transmission in its mountain region in the coming years. PMID- 26550582 TI - New Approach for the Development of Improved Traditional Medicine: Case of a Preparation of an Oral Hypoglycemic Medicine from Laportea ovalifolia (Schumach. & Thonn.) Chew. (Urticaceae). AB - A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, Laportea ovalifolia was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries. PMID- 26550584 TI - Self-archiving of Our Own Articles: Romeo and Juliet Notes. PMID- 26550583 TI - Does Size Impact Attention and Recall of Graphic Health Warnings? AB - OBJECTIVE: To evaluate the attention paid to larger sizes of graphic health warnings (GHWs) embedded within cigarette advertisements so as to assess their impacts on rural smokers. METHODS: Daily smokers (N = 298) were randomly assigned to view a cigarette advertisement with 3 conditions: 2 intervention conditions with GHW comprising 20% or 33% of the ad area, or a text-only control. Eye tracking software measured attention in milliseconds. Binary outcome mediation was conducted. RESULTS: Intervention participants spent 24% of their time viewing the GHWs, compared to 10% for control (p < .01). The odds of GHW recall in the combined (20% and 33%) intervention group were 3.3 times higher than controls. Total dwell time mediated 33% of the effect of the graphic condition on any recall. CONCLUSIONS: GHWs in 20% of cigarette advertisement space attracted significantly more attention than text-only warnings; larger GHWs did not increase attention. Attention was significantly associated with warning recall; total time viewing mediated warning recall. Tobacco ads should include GHWs to attract the attention of smokers. PMID- 26550586 TI - Knee Fusion or Above-The-Knee Amputation after Failed Two-Stage Reimplantation Total Knee Arthroplasty. AB - Prosthetic joint infection (PJI) is a serious complication of total knee arthroplasty (TKA). Control of infection after a failed two-stage TKA is not always possible, and the resolution of infection may require an above-knee amputation (AKA) or a the-knee (KF). The purpose of this review is to determine which treatment method (AKA or KF) yields better function and ambulatory status for patients after a failed two-stage reimplantation. A PubMed search related to the resolution of infection by means of an above-the-knee amputation (AKA) or a knee fusion was performed until 10 January 2015. The key words were: infected TKA and above-the-knee amputation. Five hundred and sixty-six papers were found, of which ten were reviewed because they were focused on the topic of the article. KF should be strongly considered as the treatment of choice for patients who have persistent infected TKA after a failed two-stage revision arthroplasty. Patients can walk at least inside the house, and activity of daily living independence is achieved by the patients with successful KF, although walking aids, including a shoe lift, are required. An intramedullary nail leads to better functional results than an external fixator. The functional outcome after AKA performed after TKA is poor. A substantial percentage of the patients never fit with a prosthesis, and those who are seldom obtain functional independence. Only 50% of patients are able to walk after AKA. Patients receiving KF for treating recurrent PJI after TKA have better function and ambulatory status compared to patients receiving AKA. KF must be recommended as the treatment of choice for patients who have persistent infected TKA after a failed two-stage reimplantation procedure. PMID- 26550587 TI - Correlation of Reconstructed Scaphoid Morphology with Clinical Outcomes. AB - BACKGROUND: Scaphoid malunion alters the carpal kinematics and impairs clinical outcome because of pain, weakness, restricted range of motion and predisposing the wrist joint to early osteoarthritis. The aim of this study was to evaluate the influence of the scaphoid morphological angles on clinical outcomes in patients with reconstructed scaphoid by non-vascularized bone graft. METHODS: Seventeen male patients with the mean age of 31.7+/-3.7 years and mean non-union time of 31.5+/-14.7 months were enrolled in this retrospective study. Average follow up was 48.8+/-9.4 months. At the last follow-up, the patients were evaluated clinically for pain, wrist range of motion, grip strength, and wrist functional status. They were also evaluated radiologically by wrist radiographs and computerized tomography (CT). The overall clinical outcomes were evaluated by the Cooney wrist function score. The morphology of the reconstructed scaphoids was evaluated by the lateral intrascaphoid angle, antroposterior intrascaphoid angle, dorsal cortical angle, measuring the length (mm), and height-to-length ratio on CT scan. The radiological measurements were compared against the overall clinical outcomes. RESULTS: There were 7 excellent, 7 good, 3 fair clinical results. The mean Cooney wrist function score was 83+/-4. The mean lateral intrascaphoid angle was 34.8+/-1.4 degrees, mean antroposterior intrascaphoid angle was 33.4+/-2.2 degrees, mean dorsal cortical angle was 158.3+/-4.8 degrees, mean scaphoid length was 22.1+/- 0.7 mm, and mean scaphoid height-to-length ratio was 0.74+/-0.04. There were no significant statistical correlations between the lateral intrascaphoid angles, antroposterior intrascaphoid angles, dorsal cortical angles, scaphoid lengths and scaphoid height-to-length ratios and Cooney wrist scores in the patients. CONCLUSION: In the current study, all the patients had some degree of scaphoid malunion; however, the radiological measurements of the reconstructed scaphoids did not correlate with the clinical outcomes. PMID- 26550588 TI - Normal Age-Related Alterations on Distal Radius Radiography. AB - BACKGROUND: The present study was designed to ascertain serial changes on distal radius radiographic parameters attributable to aging. METHODS: In this prospective study, the sample consisted of 120 healthy individuals who were divided into four age groups each containing 15 males and 15 females. In the two below-20-year-old groups, only ulnar variance could be investigated. Wrist radiography was taken and then parameters of the distal radius were measured and compared based on age and sex. RESULTS: Average UV was -2.48 mm and -1.6 mm in the 2-9 and 10-19-year-old age groups, respectively. Also, in the two above-20 year-old groups, the average radial inclination (RI), palmar tilt (PT), radial length (RL), and UV was 23.7o, 12.4o, 10.5 and +1.1 mm, respectively. Considering ulnar variance, no significant difference was found between the 2-9- and 10-19 year-old groups, as well as among the two above-20-year-old groups. However, a significant difference was observed between the below 20 and above 20 groups. The study results showed no significant differences between males and females in any of the study groups. DISCUSSION: There is significant ulnar variance change toward less negative ulnar variance with aging until maturity. PMID- 26550585 TI - Failure of Anterior Cruciate Ligament Reconstruction. AB - The present review classifies and describes the multifactorial causes of anterior cruciate ligament (ACL) surgery failure, concentrating on preventing and resolving such situations. The article particularly focuses on those causes that require ACL revision due to recurrent instability, without neglecting those that affect function or produce persistent pain. Although primary ACL reconstruction has satisfactory outcome rates as high as 97%, it is important to identify the causes of failure, because satisfactory outcomes in revision surgery can drop to as much as 76%. It is often possible to identify a primary or secondary cause of ACL surgery failure; even the most meticulous planning can give rise to unexpected findings during the intervention. The adopted protocol should therefore be sufficiently flexible to adapt to the course of surgery. Preoperative patient counseling is essential. The surgeon should limit the patient's expectations for the outcome by explaining the complexity of this kind of procedure. With adequate preoperative planning, close attention to details and realistic patient expectations, ACL revision surgery may offer beneficial and satisfactory results for the patient. PMID- 26550589 TI - Introduction of a New Suture Method in Repair of Peripheral Nerves Injured with a Sharp Mechanism. AB - BACKGROUND: The standard method for repair of an injured peripheal nerve is epineural repair with separate sutures. Herein we describe a method in which the nerve is sutured with continous sutures. In fact this method has not been utilized for nerve repair previously and our purpose was to compare it to the standard method. If it proved to be successful it would replace the standard method in certain circumstances. METHODS: The proposal of the clinical trial was given a reference number form the ethics comitee. 25 dogs in which the scaitic nerve was cut by a sharp blade under genaeral anesthesia were divided randomly into three groups: control (5 dogs), repair of sciatic nerve with simple sutures (10) and repair with continous sutures (10). In the control group the nerve was not repaired at all. After 6 weeks the dogs were killed and the nerve was studied by light and electronic microscopes. The amount of consumed suture material, time of repair, myelin thickness and axon diiameter were examined. Ultrastructural studies were performed to assess degeneration and regeneration findings. RESULTS: Time of repair and the amount of consumed suture material were significantly lower in the continous group (P<0.001). No difference was found with regard to light microscopy findings and regeneration was confirmed by electron microscopy in the continous group. CONCLUSION: The method described in the present study, provided a result similar to the standard method. Though undobtfully it has some limitations, can replace the standard method in many circumstances. PMID- 26550590 TI - Outcome of ACL Reconstruction and Concomitant Articular Injury Treatment. AB - BACKGROUND: Articular cartilage injuries are a common clinical problem at the time of ACL reconstruction with an incidence rate of 16-46%. Good results of ACL reconstruction combined with the treatment of chondral lesions have been published in some studies. METHOD: After statistical analysis 30 patients were selected and divided in 2 groups. The first group consisted of 15 patients with isolated ACL tear without any other concomitant injuries and the second group consisted of 15 patients with ACL tear and concomitant high grade (grade 3 or 4 of outerbridge classification) contained articular cartilage injuries during arthroscopy. Group 1 underwent ACL reconstruction and group 2 underwent ACL reconstruction combined with chondroplasty via the drilling or microfracture technique. For each patient the Lysholm knee score questionnaire was completed before surgery, 6 months and 1 year after surgery. RESULTS: The mean Lysholm knee score in both groups improves: 9.6 points after 6 months and 16.06 points after 1 year in group 1, 23.26 points after 6 months, 30.66 after 1 year in group 2, which was statistically significant (Pvalue<0.05). CONCLUSION: Improvement in the Lysholm knee score in both groups shows that ACL reconstruction with concomitant chondroplasty in high grade chondral injuries has good results with patient satisfaction and improvement in their quality of life. PMID- 26550591 TI - Functional Outcome Following Arthroscopic ACL Reconstruction with Rigid Fix: A Retrospective Observational Study. AB - BACKGROUND: No uniform consensus exists to decide type of fixation for arthroscopic anterior cruciate ligament reconstruction. Hypothsis: There is similar functional outcome after rigid fix compared to other methods of fixation which has been published. STUDY DESIGN: Retrospective observational study. METHODS: A total of 50 patients underwent arthroscopic anterior cruciate ligament reconstruction with hamstring tendons using femoral Rigid fix cross-pin and interference screw tibial fixation. The evaluation methods were clinical examination, IKDC scores, Lysholm and pre injury and post reconstruction Tegner score. Patients were followed up from minimum of 6 months to 4 year seven months. RESULTS: C In our study of sample size 50 we found that mean age of patients was 30.8 Years with male preponderance. Mean post operative IKDC and Lysholm score has been 75.6 and 84.4 respectively. Mean Tegner pre-injury score and post reconstruction score has been 5.4 and 4.26. Box plot comparison of pre injury and post operativeTegner score reveals a statistically significant difference with respect to paired t test P<0.001. CONCLUSIONS: Arthroscopic anterior cruciate ligament reconstruction with femoral rigid fix cross pins and tibial interference screws results in comparable short term to midterm functional results compared to other types of fixation. PMID- 26550592 TI - Risk of Spermatic Cord Injury During Anterior Pelvic Ring and Acetabular Surgery: An Anatomical Study. AB - BACKGROUND: Anterior pelvic ring surgery includes a variety of plating techniques and insertion of retrograde superior pubic ramus screws. Anterior acetabular surgery also includes fixation through an ilioinguinal or Stoppa approach. These exposures risk injury to the spermatic cord and accompanying genital branch of the genitofemoral nerve. The primary aim of this study was to identify the distance between the midline and the spermatic cords in adult male cadaveric specimens. The secondary aim was to determine spermatic cord diameters and measure the distance between the spermatic cord and implant during instrumentation of a retrograde superior pubic ramus medullary screw. METHODS: Extended Pfannenstiel and Stoppa approaches were performed on 18 embalmed male cadavers bilaterally. Spermatic cord characteristics were recorded and a number of measurements were performed to determine the distance of implants and the midline from the spermatic cord. RESULTS: The average distance between the midline and spermatic cords was 34.2 mm. The average distance between the spermatic cord and implant was 18.2 mm. Eleven of the thirty-six dissections had abnormalities including cord lipomas and inguinal hernias. The average cord diameter was 18.6 mm. The average cord diameter in those with abnormalities was 24.9 mm and 16 mm in those without abnormalities, this difference was statistically significant. DISCUSSION: Due to the proximity of the spermatic cord, the surgeon should either formally expose the cord or limit lateral dissection from the midline during Pfannenstiel and Stoppa exposures. Similarly, the surgeon should use soft-tissue sleeves and oscillating drills to avoid injury to the contralateral spermatic cord during the insertion of retrograde superior pubic ramus medullary screws. PMID- 26550593 TI - Inguinal Abnormalities in Male Patients with Acetabular Fractures Treated Using an Ilioinguinal Exposure. AB - BACKGROUND: Surgeons performing an ilioinguinal exposure for acetabular fracture surgery need to be aware of aberrant findings such as inguinal hernias and spermatic cord lesions. The purpose of this study is to report these occurrences in a clinical series of adult males undergoing acetabular fracture fixation and a series of adult male cadavers. The secondary aim is to characterize these abnormalities to aid surgeons in detecting these abnormalities preoperatively and coordinating a surgical plan with a general surgeon. METHODS: Clinical study- Retrospective review of treated acetabular fractures through an ilioinguinal approach. Incidence of inguinal canal and spermatic cord abnormalities requiring general surgery consultation were identified. Corresponding CT scans were reviewed and radiographic characteristics of the spermatic cord abnormalities and/or hernias were noted. Cadaveric study- 18 male cadavers dissected bilaterally using an ilioinguinal exposure. The inguinal canal and the contents of the spermatic cord were identified and characterized. RESULTS: Clinical Study- 5.7% (5/87) of patients had spermatic cord lesion and/or inguinal hernia requiring general surgical intervention. Preoperative pelvic CT scan review identified abnormalities noted intraoperatively in four of the five patients. Cord lipomas visualized as enlargements of the spermatic cord with homogeneous density. Hernias visualized as enlarged spermatic cords with heterogeneous density. Cadaver Study- 31% (11/36) of cadavers studied had spermatic cord and/or inguinal canal abnormalities. Average cord diameter in those with abnormalities was 24.9 mm (15-28) compared to 16 mm (11-22) in normal cords, which was statistically significant. DISCUSSION: The clinical and cadaveric findings emphasize the importance of understanding inguinal abnormalities and the value of detecting them preoperatively. The preoperative pelvic CT scans were highly sensitive in detecting inguinal abnormalities. PMID- 26550594 TI - Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery. AB - BACKGROUND: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient's satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. METHODS: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA) with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5ug/kg sublingually) and morphine (0.2mg/kg intravenously). Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes), and in the ward (at 3, 6 and 12 hours). SPSS version 19 software was used for data analysis and the significance level was set at P<0.05. RESULTS: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7+/-16.2 years. There was no significant difference between the two groups in terms of baseline characteristics. Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P<0.001). Postoperative mean heart rate in the buprenorphine group was four beats lower than the morphine group (P<0.001). Also, in the buprenorphine 48.6% and in the morphine group 86.7% of cases were conscious in recovery (P=0.001) with a higher rate of pruritus in the latter group (P=0.001). CONCLUSION: Sublingual buprenorphine administration before anesthesia induction in closed reduction surgery can lead to better postoperative pain control in comparison to intravenous morphine. Due to simple usage and longer postoperative sedation, sublingual buprenorphine is recommended as a suitable drug in closed reduction surgery. PMID- 26550595 TI - Assessment of Correlation Between MRI and Arthroscopic Pathologic Findings in the Shoulder Joint. AB - BACKGROUND: The objective of this study was to determine the diagnostic value of magnetic resonance imaging for shoulder joint pathologies and then compare the results with arthroscopy, the standard for joint diagnosis. METHODS: In this cross-sectional study, 80 patients with shoulder joint disorders, who underwent final arthroscopy, were studied. Based on patients' medical history and physical examinations, shoulder MRI was requested if paraclinical investigations were. If non-surgical therapies failed, arthroscopy of the affected shoulder was done and the same structures were inspected. Subsequently, sensitivity, specificity, and positive and negative predictive values (PPV) and (NPV) of MRI were determined by arthroscopy comparisons. RESULTS: The highest sensitivity, specificity, PPV and NPV were found in MRI pathology reports that included: Hill-Sach lesion (0.910), infraspinatus tendon (0.985), supraspinatus tendon (0.930), and biceps tendon (0.954), respectively. Rotator interval (0.250), biceps labrum complex (0.805), subscapularis tendon (0.538) and anterior labrum lesions (0.604) had the lowest sensitivity, specificity, PPV and NPV, respectively. CONCLUSION: The results showed that MRI can be a useful tool in ruling out possible abnormalities in the shoulder and to give clues to the most probable diagnosis. Although knowing some practical skills in order to successfully perform the procedure and experience of the radiologist with suitable feedback by surgeon is necessary. PMID- 26550596 TI - Bacille Calmette-Guerin Osteomyelitis. AB - BACKGROUND: Tuberculosis is an essential problem for healthcare systems especially in developing countries. All newborns are given Bacillus Calmette Guerin (BCG) vaccine in Iran which is prepared from live bovine tuberculosis bacillus, and is given to protect against tuberculosis. Osteomyelitis secondary to BCG vaccination is rare and usually involves epiphysis of long tubular bones. METHODS: 4 patients, 3 males and a female entered this study and were between 11 to 24 months old. The involved bones were first metatarsi, talus, humerus and tibia bone. The main radiologic finding was lytic lesion with cortical destruction and periosteal reaction. RESULTS: 3 patients underwent core needle biopsy and the one with the proximal tibia involvement, underwent open surgery. Pathology report suggested granulomatous osteomyelitis and typical caseous necrosis compatible with tuberculosis. Surgical treatment for these patients was curettage and debridement of the bone lesion and involved tissues around. The patients got standard anti TB pharmacotherapy, were completely cured and no short term complication was seen in a one year follow up. CONCLUSION: BCG osteomyelitis and cold abscess, should be kept in mind when assessing a child presenting chronic symptoms like pain, limping or local swelling of extremities. The long interval time between BCG vaccination and outbreak of the culture-negative abscess is a major point which emphasizes on pathologic evaluation. Image guided tissue biopsy and PCR studies confirm diagnosis. Early use of a surgical curettage and debridement along with chemotherapy soon afterwards, enabled these children to enjoy a satisfactory clinical outcome. PMID- 26550597 TI - Unusual Presentation of Synovial Sarcoma as Meniscal Cyst: A Case Report. AB - Periarticular cyst and cystic soft tissue lesion around the knee are common. Synovial sarcoma is a rare and malignant soft tissue tumor accounting for approximately 5% of soft tissue sarcoma. A case is presented where a lesion adjacent to the joint line of the knee was diagnosed clinically and on imaging as a meniscal cyst. MRI signal was homogenous and no concomitant meniscal tears were seen. The tissue diagnosis was monophasic synovial sarcoma. PMID- 26550598 TI - First Carpometacarpal Joint Dislocation and Review of Literatures. AB - Dislocation of the first carpometacarpal (CMC) is a rare occurrence. Treatment of this dislocation varies from closed reduction and casting to ligament repair. Neglected dislocation or incomplete reduction of the 1(st) CMC cause chronic instability and painful arthritis, muscle imbalance and decreased grip force. In our study 6 patients is evaluated that were visited in less than 24 hours from their injury. All were primarily reduced and except one patient later injured ligament were repaired. All patient after 6 months had normal range of motion without pain and they had not any complaint. Stability at the 1(st) CMC joint is dependent on static and dynamic forces. However, dislocation of the 1(st) CMC occur rare, but important function of the thumb specially in gripping and grasping makes it a significant problem. Injured ligament should repair for increased stability of 1(st) CMC joint, because neglected dislocation or incomplete reduction cause chronic instability and painful arthritis. PMID- 26550599 TI - Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. AB - Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1]. In this study, we assess the susceptibility of DC to lower concentrations of long chain bases. 0.2-10.0 uM long-chain bases and GML were not cytotoxic to DC; 40.0-80.0 uM long-chain bases, but not GML, were cytotoxic for DC; and 80.0 uM long-chain bases were cytotoxic to DC and induced cellular damage and death in less than 20 mins. Overall, the LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections. PMID- 26550600 TI - Assessment of current mass spectrometric workflows for the quantification of low abundant proteins and phosphorylation sites. AB - The data described here provide a systematic performance evaluation of popular data-dependent (DDA) and independent (DIA) mass spectrometric (MS) workflows currently used in quantitative proteomics. We assessed the limits of identification, quantification and detection for each method by analyzing a dilution series of 20 unmodified and 10 phosphorylated synthetic heavy labeled reference peptides, respectively, covering six orders of magnitude in peptide concentration with and without a complex human cell digest background. We found that all methods performed very similarly in the absence of background proteins, however, when analyzing whole cell lysates, targeted methods were at least 5-10 times more sensitive than directed or DDA methods. In particular, higher stage fragmentation (MS3) of the neutral loss peak using a linear ion trap increased dynamic quantification range of some phosphopeptides up to 100-fold. We illustrate the power of this targeted MS3 approach for phosphopeptide monitoring by successfully quantifying 9 phosphorylation sites of the kinetochore and spindle assembly checkpoint component Mad1 over different cell cycle states from non-enriched pull-down samples. The data are associated to the research article 'Evaluation of data-dependent and data-independent mass spectrometric workflows for sensitive quantification of proteins and phosphorylation sites' (Bauer et al., 2014) [1]. The mass spectrometry and the analysis dataset have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD000964. PMID- 26550602 TI - Application of Response Surface Methodology for Modeling of Postweld Heat Treatment Process in a Pressure Vessel Steel ASTM A516 Grade 70. AB - This research studied the application of the response surface methodology (RSM) and central composite design (CCD) experiment in mathematical model and optimizes postweld heat treatment (PWHT). The material of study is a pressure vessel steel ASTM A516 grade 70 that is used for gas metal arc welding. PWHT parameters examined in this study included PWHT temperatures and time. The resulting materials were examined using CCD experiment and the RSM to determine the resulting material tensile strength test, observed with optical microscopy and scanning electron microscopy. The experimental results show that using a full quadratic model with the proposed mathematical model is YTS = -285.521 + 15.706X1 + 2.514X2 - 0.004X1(2) - 0.001X2(2) - 0.029X1X2. Tensile strength parameters of PWHT were optimized PWHT time of 5.00 hr and PWHT temperature of 645.75 degrees C. The results show that the PWHT time is the dominant mechanism used to modify the tensile strength compared to the PWHT temperatures. This phenomenon could be explained by the fact that pearlite can contribute to higher tensile strength. Pearlite has an intensity, which results in increased material tensile strength. The research described here can be used as material data on PWHT parameters for an ASTM A516 grade 70 weld. PMID- 26550601 TI - Genetic diversity and population structure in Physalis peruviana and related taxa based on InDels and SNPs derived from COSII and IRG markers. AB - The genus Physalis is common in the Americas and includes several economically important species, among them Physalis peruviana that produces appetizing edible fruits. We studied the genetic diversity and population structure of P. peruviana and characterized 47 accessions of this species along with 13 accessions of related taxa consisting of 222 individuals from the Colombian Corporation of Agricultural Research (CORPOICA) germplasm collection, using Conserved Orthologous Sequences (COSII) and Immunity Related Genes (IRGs). In addition, 642 Single Nucleotide Polymorphism (SNPs) markers were identified and used for the genetic diversity analysis. A total of 121 alleles were detected in 24 InDels loci ranging from 2 to 9 alleles per locus, with an average of 5.04 alleles per locus. The average number of alleles in the SNP markers was two. The observed heterozygosity for P. peruviana with InDel and SNP markers was higher (0.48 and 0.59) than the expected heterozygosity (0.30 and 0.41). Interestingly, the observed heterozygosity in related taxa (0.4 and 0.12) was lower than the expected heterozygosity (0.59 and 0.25). The coefficient of population differentiation FST was 0.143 (InDels) and 0.038 (SNPs), showing a relatively low level of genetic differentiation among P. peruviana and related taxa. Higher levels of genetic variation were instead observed within populations based on the AMOVA analysis. Population structure analysis supported the presence of two main groups and PCA analysis based on SNP markers revealed two distinct clusters in the P. peruviana accessions corresponding to their state of cultivation. In this study, we identified molecular markers useful to detect genetic variation in Physalis germplasm for assisting conservation and crossbreeding strategies. PMID- 26550603 TI - Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption. AB - Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S box design and key generation significantly reduce the computational cost of video encryption with no compromise in security. PMID- 26550604 TI - In Vitro Seeds Germination and Seedling Growth of Bambara Groundnut (Vigna subterranea (L.) Verdc. (Fabaceae)). AB - Bambara groundnut (Vigna subterranea (L.) Verdc.) is an indigenous grain legume. It occupies a prominent place in the strategies to ensure food security in sub Saharan Africa. Development of an efficient in vitro regeneration system, a prerequisite for genetic transformation application, requires the establishment of optimal conditions for seeds germination and plantlets development. Three types of seeds were inoculated on different basal media devoid of growth regulators. Various strengths of the medium of choice and the type and concentration of carbon source were also investigated. Responses to germination varied with the type of seed. Embryonic axis (EA) followed by seeds without coat (SWtC) germinated rapidly and expressed a high rate of germination. The growth performances of plantlets varied with the basal medium composition and the seeds type. The optimal growth performances of plants were displayed on half strength MS basal medium with SWtC and EA as source of seeds. Addition of 3% sucrose in the culture medium was more suitable for a maximum growth of plantlets derived from EA. PMID- 26550605 TI - Modeling and Simulation of Offshore Wind Power Platform for 5 MW Baseline NREL Turbine. AB - This paper presents the modeling and simulation of offshore wind power platform for oil and gas companies. Wind energy has become the fastest growing renewable energy in the world and major gains in terms of energy generation are achievable when turbines are moved offshore. The objective of this project is to propose new design of an offshore wind power platform. Offshore wind turbine (OWT) is composed of three main structures comprising the rotor/blades, the tower nacelle, and the supporting structure. The modeling analysis was focused on the nacelle and supporting structure. The completed final design was analyzed using finite element modeling tool ANSYS to obtain the structure's response towards loading conditions and to ensure it complies with guidelines laid out by classification authority Det Norske Veritas. As a result, a new model of the offshore wind power platform for 5 MW Baseline NREL turbine was proposed. PMID- 26550606 TI - Context dependent utilization of serine in cancer. AB - Serine and glycine have diverse biological functions but the general and context dependent utilizations of these nutrients in cancer are unknown. Our recent work integrates genomics data and isotope tracing using computational tools to study serine utilization across multiple cancer and normal human samples. PMID- 26550607 TI - Corpora Amylacea in Neurodegenerative Diseases: Cause or Effect? AB - The presence of corpora amylacea (CA) in the CNS is associated with both normal aging and neurodegenerative conditions including Alzheimer's disease (AD) and vascular dementia (VaD). CA are spherical bodies ranging in diameter (10-50 MUm) and whose origin has been documented to be derived from both neural and glial sources. CA are reported to be primarily composed of glucose polymers, but approximately 4% of the total weight of CA is consistently composed of protein. CA are typically localized in the subpial, periventricular and perivascular regions within the CNS. The presence of CA in VaD has recently been documented and of interest was the localization of CA within the hippocampus proper. Despite numerous efforts, the precise role of CA in normal aging or disease is not known. The purpose of this mini review is to highlight the potential function of CA in various neurodegenerative disorders with an emphasis on the potential role if any these structures may play in the etiology of these diseases. PMID- 26550609 TI - The New National Healthcare Safety Network (NHSN) Healthcare Personnel Influenza Vaccination Measure. PMID- 26550608 TI - Magnetic Resonance Imaging and Spectroscopy: Application to Experimental Neuro Oncology. AB - The development and use of animal brain tumor models over the past 25 years has helped to advance our understanding of both tumor biology and the effectiveness of new therapeutic approaches. The application of MRI and MRS as noninvasive tools for in vivo studies of intracerebral tumor models provides unique possibilities for furthering our knowledge of brain cancer. This article provides a brief background of traditional techniques used to evaluate growth and treatment efficacy in rodent brain tumor models and overviews the use of MR for quantitating intracerebral tumor growth kinetics and therapeutic response of experimental brain tumors from work conducted in this laboratory. The application of MRI and MRS in rodent brain tumor models for evaluation of novel therapeutic approaches, including gene transfer technology, is discussed. Finally, initial results with diffusion MRI for monitoring the treatment of brain tumors is introduced. PMID- 26550610 TI - Determination of Crystalline Silica in Dust at Low Concentrations by Low Temperature Infrared Spectrometry. AB - The American Conference of Governmental Industrial Hygienists (ACGIH) accepted a lower threshold limit value (TLV) for respirable crystalline silica (RCS) exposure of 25 MUg/m3, half of the previous TLV. This change is problematic because the current standard sampling and measurement practices used by NIOSH, OSHA, and MSHA are not sensitive enough to allow an analyst to confidently determine samples acquired near the TLV. In response to this need for a more sensitive method to analyze respirable dust filter samples for crystalline silica, a modification of current NIOSH infrared spectrometric methods is being developed. The additional sensitivity is gained by performing the infrared absorbance measurements at 77 K where absorbance peaks are more intense by virtue of being narrower. A quick-change cryostat has been fabricated such that a sample can be introduced to the spectrometer and cooled to 77 K in 5 min, interrogated for 1 min, and removed and the cryostat readied for another sample in 2 min, for a turnaround time of 8 min per sample, which is brief compared to the time required to prepare and redeposit a sample. Therefore, samples can be acquired and interrogated with legacy samplers, filters, pumps, spectrometers, and sample preparation, the only modification being the addition of a cryostat to the spectrometer. Preliminary experiments demonstrate that the peak-to-background ratio of the quartz signature band near 800 cm-1 increases by approximately 50 % on cooling from room temperature to 77 K. The slopes of the calibration curve derived from standards interrogated at both room temperature and 77 K indicate that the low-temperature method is approximately 25 % more sensitive. PMID- 26550611 TI - The Development of Emotional and Behavioral Control in Early Childhood: Heterotypic Continuity and Relations to Early School Adjustment. AB - We examined heterotypic continuity of emotional and behavioral control (EBC) across early childhood and related early manifestations of EBC to children's school adjustment in 310 low-income, ethnically diverse boys. Multiple informants and methods were used to measure different indicators of EBC at 18, 24, 42, and 60 months, which were chosen to reflect salient regulatory challenges children face across development. Teachers rated boys' externalizing and internalizing behaviors, and social skills at 72 months. Results indicated a modest degree of heterotypic continuity of EBC, with different constructs of EBC associated between adjacent time points and, in some instances, across more distant time points. Further, children who had struggled with early EBC demonstrated higher externalizing problems and lower social skills in school. Findings suggest that early deficits in EBC may be a target for early identification and prevention, as they may forecast continued difficulty in later-developing EBC skills and socioemotional problems. PMID- 26550612 TI - Motion Compensated Abdominal Diffusion Weighted MRI by Simultaneous Image Registration and Model Estimation (SIR-ME). AB - Non-invasive characterization of water molecule's mobility variations by quantitative analysis of diffusion-weighted MRI (DW-MRI) signal decay in the abdomen has the potential to serve as a biomarker in gastrointestinal and oncological applications. Accurate and reproducible estimation of the signal decay model parameters is challenging due to the presence of respiratory, cardiac, and peristalsis motion. Independent registration of each b-value image to the b-value=0 s/mm(2) image prior to parameter estimation might be sub-optimal because of the low SNR and contrast difference between images of varying b-value. In this work, we introduce a motion-compensated parameter estimation framework that simultaneously solves image registration and model estimation (SIR-ME) problems by utilizing the interdependence of acquired volumes along the diffusion weighting dimension. We evaluated the improvement in model parameters estimation accuracy using 16 in-vivo DW-MRI data sets of Crohn's disease patients by comparing parameter estimates obtained using the SIR-ME model to the parameter estimates obtained by fitting the signal decay model to the acquired DW-MRI images. The proposed SIR-ME model reduced the average root-mean-square error between the observed signal and the fitted model by more than 50%. Moreover, the SIR-ME model estimates discriminate between normal and abnormal bowel loops better than the standard parameter estimates. PMID- 26550614 TI - [Editorial Comment of the article: The second kidney transplantation in Spain]. PMID- 26550613 TI - Multi-scale Heat Kernel based Volumetric Morphology Signature. AB - Here we introduce a novel multi-scale heat kernel based regional shape statistical approach that may improve statistical power on the structural analysis. The mechanism of this analysis is driven by the graph spectrum and the heat kernel theory, to capture the volumetric geometry information in the constructed tetrahedral mesh. In order to capture profound volumetric changes, we first use the volumetric Laplace-Beltrami operator to determine the point pair correspondence between two boundary surfaces by computing the streamline in the tetrahedral mesh. Secondly, we propose a multi-scale volumetric morphology signature to describe the transition probability by random walk between the point pairs, which reflects the inherent geometric characteristics. Thirdly, a point distribution model is applied to reduce the dimensionality of the volumetric morphology signatures and generate the internal structure features. The multi scale and physics based internal structure features may bring stronger statistical power than other traditional methods for volumetric morphology analysis. To validate our method, we apply support vector machine to classify synthetic data and brain MR images. In our experiments, the proposed work outperformed FreeSurfer thickness features in Alzheimer's disease patient and normal control subject classification analysis. PMID- 26550615 TI - [Bone metastasis of prostatic adenocarcinoma. Image collection]. PMID- 26550616 TI - [Urothelial transitional cell carcinoma located in fossa navicularis]. PMID- 26550617 TI - [Pyonephrosis secondary to bladder catheter misplaced in the pelvic ureter]. PMID- 26550618 TI - [Dr. Fernando Arocena Lanz]. PMID- 26550619 TI - [Renal hematoma in tuberous sclerosis patient with several renal angiomyolipomas]. PMID- 26550621 TI - [Editorial]. PMID- 26550620 TI - [Not Available]. PMID- 26550622 TI - Giant cyst of the prostate. PMID- 26550623 TI - [Urethrovesical redo anastomosis after accidental removal of the urethral catheter after radical prostatectomy]. PMID- 26550624 TI - [Non-invasive ventilation]. AB - Within the last decade the use of non-invasive ventilation has expanded. This article reviews the studies on non-invasive ventilation in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD), cardiogenic pulmonary oedema, acute respiratory distress syndrome, asthma and neuromuscular disease. Its beneficial effect has primarily been found in exacerbations of COPD where it reduces mortality with a number needed to treat of ten when added to standard medical treatment. No other conclusive evidence of the superiority of non-invasive ventilation compared to other modalities has been shown. PMID- 26550626 TI - [Growth hormone deficiency in children]. AB - Growth hormone (GH) deficiency may be of congenital origin and may present with typical clinical signs and symptoms very early in postnatal life, but may also present later during childhood with growth deceleration. In a short-statured child suspected of GH deficiency, diagnostic procedures include appropriate auxological measurements using updated national growth references, bone age determination, and biochemical evaluation. GH dose is adjusted every three months based on height changes and serum insulin-like growth factor-I concentration. After cessation of linear growth, GH secretion should be re-evaluated during transitional care from a paediatric to an adult endocrinological setting. PMID- 26550625 TI - [Optimized thiopurine treatment in chronic inflammatory bowel disease]. AB - Thiopurines are effective in maintaining remission in chronic inflammatory bowel diseases, but incomplete response or side effects are common during standard-dose treatment. In this article thiopurine metabolism and pharmacogenetic aspects are summarized showing their benefits in improving therapy in chronic inflammatory bowel disease. An increasing body of evidence suggests that a large part of the observed non-pancreatic side effects and poor responses can be solved by tailoring thiopurine therapy using measurement of thiopurine methyltransferase and metabolites and by using a combination therapy with low-dose thiopurines and allopurinol. PMID- 26550627 TI - [Diagnosis and treatment of cerebral venous sinus thrombosis]. AB - Thrombosis of the cerebral sinuses most often affects younger adults. Headache is a common complaint and can be accom-panied by vomiting and papilloedema. The diagnosis rests on magnetic resonance imaging and the treatment consists of heparin or low-molecular weight heparin followed by vitamin K antagonists for three months or more. In fulminant cases local thrombolysis is administered, while symptomatic treatment for increased intracranial pressure is given. In retrospective analyses this approach has been associated with a good outcome - even in cases treated by decompressive craniectomy. PMID- 26550628 TI - [A three-day course can increase knowledge and interest in disaster medicine for medical students]. AB - The incidence of disasters increases and the need for physicians with an interest in disaster medicine is essential. As an early introduction of disaster medicine, medical students from Denmark, members of the Students' Society for Anesthesiology and Traumatology, participated on a three-day course, Trauma Days 2013, with full-scale simulations. The students underwent debriefings and questionnaires were handed out. 94% of the students increased their interest in disaster medicine. PMID- 26550629 TI - [Clinical communication skills training is an educational challenge]. AB - This qualitative study presents results from a development project of clinical communication skills training for physicians in a paediatric ward. Overall, the doctors express that the training positively supports their clinical work and that it provides a model for discussing communication challenges with colleagues. Challenges, however, are time constraints and overcoming conventional hierarchical structures. Prerequisites for ward-based communication training thus are: a suitable timeframe, use of a structured feedback model, managerial backup, and support from external expertise. PMID- 26550630 TI - [Early Warning Score in primary care in Denmark]. AB - This study investigates the implementation of Early Warning Score in primary care. Infections such as pneumonia or urinary tract infections are more frequent in older age and mortality increases with age. Early diagnosis of such conditions is thus important. This study showed that Early Warning Score in primary care is adequate to trace elderly in need of medical assistance. At a score <= 2 24% were visited by a doctor or admitted directly. At a score >= 5 this number increased to 45%. At a score <= 5 11% were admitted to hospital and at a score >= 5 31% were admitted to hospital. PMID- 26550631 TI - [Shared decision making in psychiatry]. AB - In the paradigm of recovery-oriented care in mental health the central decision model is shared decision making (SDM). In the article we describe the model of SDM and the reason why it has been identified as important in mental health care. We also review the central literature of SDM in mental health and some of the decision aids just beginning to be developed to enhance SDM, thereby pointing to the need of documenting the effect of using decision aids and to further research on the effect of SDM on the recovery process of people in mental health care. PMID- 26550632 TI - [Posttraumatic stress disorder is correlated to irritable bowel syndrome]. AB - Stress influences the whole body, including the gut. Irritable bowel syndrome (IBS) is a syndrome characterized by gastrointestinal symptoms, with the absence of clinical signs. IBS is seen in several psychiatric co-morbidities. Only few studies have examined the association between IBS and posttraumatic stress disorder (PTSD). There are several hypotheses of how this association can be explained, e.g. oxytocin dysregulation, hypothalamic-pituitary-adrenal axis dysfunction, the vulnerability of the patient group, post-infectious irritable bowel and side effects of the medical treatment of PTSD. PMID- 26550633 TI - [In Process Citation]. PMID- 26550634 TI - [In Process Citation]. PMID- 26550635 TI - [Not Available]. PMID- 26550636 TI - [Not Available]. PMID- 26550637 TI - Getting to know Dr. Paul Sweeney. PMID- 26550638 TI - [Not Available]. PMID- 26550639 TI - [Not Available]. PMID- 26550640 TI - [In Process Citation]. PMID- 26550641 TI - [Not Available]. PMID- 26550642 TI - [In Process Citation]. PMID- 26550643 TI - In Memoriam: David B. Gray, PhD, Scientist, Colleague, and Advocate. PMID- 26550644 TI - Measurement Characteristics and Clinical Utility of the Clinical Test of Sensory Interaction on Balance (CTSIB) and Modified CTSIB in Individuals With Vestibular Dysfunction. PMID- 26550645 TI - [PENILE PARAFFINOMA: RECONSTRUCTIVE SURGERY WITH COLLAGEN MATRIX AND SKIN GRAFTS]. PMID- 26550646 TI - [Not Available]. PMID- 26550647 TI - Retraction notice to "High-mobility group protein B1 (HMGB1) is a novel biomarker for human ovarian cancer" [Gynecol. Oncol. 126 (2012) 109-117]. PMID- 26550648 TI - [Hotspots and difficulties of clinical and basic research in cholestatic liver disease]. PMID- 26550649 TI - [Diagnosis and treatment of cholestatic liver disease]. PMID- 26550651 TI - [Individualized treatment of biliary liver abscess: report of 19 cases]. PMID- 26550650 TI - [CDR3 spectratyping analysis and complementary decision area 3 sequence determination for CD4+CD25+ Tregs in patients with chronic hepatitis B]. PMID- 26550652 TI - [Treatment of esophageal and gastric varices by balloon-occluded retrograde transvenous obliteration using lauromacrogol foam sclerotherapy]. PMID- 26550653 TI - [Diabetic retinopathy induced by PEG-IFN-alpha2a plus ribavirin in chronic hepatitis C: a literature review]. PMID- 26550654 TI - [Diagnosis and treatment of portal hypertension caused by superior mesenteric arteriovenous fistula]. PMID- 26550655 TI - Brien Anthony Holden, Ph.D., D.Sc., O.A.M. January 6, 1942 - July 27, 2015: Beloved Husband, Dad, Grandfather, Brother, Friend, Mentor, and Colleague. PMID- 26550656 TI - [Not Available]. PMID- 26550657 TI - A tribute to Professor Wan-Yu Chen. PMID- 26550658 TI - Productivity and Impact of the Top 100 Cited Huntington's Disease Investigators. AB - Huntington's disease (HD), research has grown dramatically over the last 25 years of research to the point where an analysis of productivity is warranted. We have compiled a list of the 100 most-cited researchers in HD together with H-Indices as a means to assess productivity and impact over the last 25 years. We also present a table of the most cited researchers of the last decade for comparison. PMID- 26550659 TI - Understanding the pressures on a DAO. PMID- 26550660 TI - Mental health nursing--'a good fit'. PMID- 26550661 TI - Taking the deep breath of courage. PMID- 26550662 TI - Recognising the right of Maori to health. PMID- 26550663 TI - Increasing organ donation among American Indians. PMID- 26550664 TI - 'Our communities are constantly in grief'. PMID- 26550666 TI - Mental health: Including a focus on physical health. PMID- 26550665 TI - Gerontology: Older people at risk of depression. PMID- 26550667 TI - Future employment law changes must address growing wealth gap--lawyer. PMID- 26550668 TI - Aged care: Deal reached with largest provider. PMID- 26550669 TI - Aged care: 'Ground-breaking' pay increase. PMID- 26550670 TI - Primary health care: Two national deals reached. PMID- 26550671 TI - Parliament 'unsafe' place to work, according to EEO Commissioner. PMID- 26550672 TI - DHBs: South Canterbury to quit aged care. PMID- 26550673 TI - Private hospitals: Proposed deal for hospices. PMID- 26550674 TI - Poor planning, communication lead to missteps in care of Ebola patient. AB - A panel of experts examining the diagnosis and care of Thomas Eric Duncan, a patient diagnosed with Ebola Virus Disease (EVD) in the United States in 2014, and the cases of two nurses who contracted EVD while caring for Duncan, has unveiled its findings along with recommendations to prevent many of the missteps that occurred during the crisis. While the independent panel was convened at the direction of Texas Health Resources, the parent company of Texas Health Presbyterian Hospital in Dallas, observers and the panel itself note that the findings should help hospitals, EDs, and communities across the country prepare for the next infectious disease event. The expert panel noted that ED personnel relied too heavily on the electronic medical record (EMR) to communicate with other members of the care team, and that important information, such as the patient's travel history, was not prioritized or highlighted in the EMR. Patient satisfaction and other operational objectives took precedence over patient safety during Duncan's ED visit, according to the expert panel's findings. The clinical team failed to pick up on changes in the patient's clinical status, missing an opportunity to re-evaluate Duncan and properly diagnosis him with EVD during his first visit to the ED. Confusion over the roles and responsibilities of local and federal health authorities, and inadequate preparation for an infectious disease event led to missteps. The expert panel suggests conducting practice drills that include all participating organizations, and hospital leaders should consider infectious disease threats as well as other types of disasters. PMID- 26550675 TI - Travel history key to picking up on signs of bubonic plague. AB - Health officials note an uptick in cases of bubonic plague in the United States this year, with at least 12 reported human cases reported since April 1. The CDC notes that healthcare providers should consider plague in patients who have traveled to plague-endemic areas and exhibit fever, headache, chills, weakness, and one or more swollen or tender and painful lymph nodes, referred to as buboes. Officials note that the disease rarely passes from person to person, but that this is a concern with patients who have developed the pneumonic form of the disease. Health officials note that in recent years there has been an average of seven cases of human plague each year in the United States, and that most of these cases are the bubonic form of the illness. Four patients confirmed to have plague this year have died, including the most recent case, a Utah man in his 70s. Most cases of plague in the United States occur in two regions. The first includes northern New Mexico, northern Arizona, and southern Colorado, and the second includes California, southern Oregon, and far western Nevada. When plague is suspected, treatment with antibiotics should begin immediately. PMID- 26550676 TI - Interdisciplinary mistrust, communication breakdowns cited in survey of ED handoffs. AB - Both emergency and inpatient physicians agree that miscommunication during interunit handoffs can compromise patient care and that sequential handoffs are particularly problematic, according to a new study conducted at the University of Nebraska Medical Center (UNMC) in Omaha, NE. The study highlights physician survey data showing that there is mistrust between inpatient and emergency physicians, and that which provider is responsible for patient care can be unclear when a verbal handoff is made. To make improvements, UNMC has been piloting a tool aimed at standardizing verbal and written handoff communications. Nearly a third of all the participating physicians surveyed reported having handoff-related adverse events, and most put the blame on ineffective communication. Ninety-four percent of emergency physicians surveyed indicated that they had to defend their clinical decisions at least some of the time. The admitting physicians largely validated this concern, with more than 25% noting that they usually disagree with decisions made in the ED. Using the situation, background, assessment, recommendation (SBAR) form of communication as a starting point, an intervention tool aims to streamline handoff communications, both verbally and in the electronic medical record. PMID- 26550677 TI - Synthesis of 2,3-Dihydro-1H-azepine and 1H-Azepin-2(3H)-one Derivatives From Intramolecular Condensation between Stable Tertiary Enamides and Aldehydes. AB - A new strategy to construct 2,3-dihydro-1H-azepine and 1H-azepin-2(3H)-one heterocyclic rings is reported based on emerging tertiary enamide synthons. Under very mild conditions employing BBr3 as a Lewis acid catalyst and P2O5 as an additive, tertiary enamides that contain a formyl group underwent highly efficient and scalable intramolecular cyclic condensation to afford diverse 2,3 dihydro-1H-azepine and 1H-azepin-2(3H)-one derivatives in 71-96% yields. The reaction proceeded most probably through a nucleophilic addition of enamides to aldehyde, deprotonation, and dehydration cascade. Application of the method in the synthesis of dihydro-azepino[2,1-a]isoindol-5-ones, the core structure of naturally occurring lennoxamine, was also demonstrated. PMID- 26550678 TI - Potassium-Ion Oxygen Battery Based on a High Capacity Antimony Anode. AB - Recent investigations into the application of potassium in the form of potassium oxygen, potassium-sulfur, and potassium-ion batteries represent a new approach to moving beyond current lithium-ion technology. Herein, we report on a high capacity anode material for use in potassium-oxygen and potassium-ion batteries. An antimony-based electrode exhibits a reversible storage capacity of 650 mAh/g (98% of theoretical capacity, 660 mAh/g) corresponding to the formation of a cubic K3Sb alloy. The Sb electrode can cycle for over 50 cycles at a capacity of 250 mAh/g, which is one of the highest reported capacities for a potassium-ion anode material. X-ray diffraction and galvanostatic techniques were used to study the alloy structure and cycling performance, respectively. Cyclic voltammetry and electrochemical impedance spectroscopy were used to provide insight into the thermodynamics and kinetics of the K-Sb alloying reaction. Finally, we explore the application of this anode material in the form of a K3Sb-O2 cell which displays relatively high operating voltages, low overpotentials, increased safety, and interfacial stability, effectively demonstrating its applicability to the field of metal oxygen batteries. PMID- 26550679 TI - Predicting probation revocation and residential facility placement at juvenile probation review hearings: Youth-specific and hearing-specific factors. AB - Although most justice-involved youth receive probation as a community-based alternative to residential facility placement, many of these youth are later committed to residential facilities when their probation dispositions are revoked at probation review hearings. The limited research investigating predictors of facility placement following juvenile probation revocation has focused primarily on youth-specific factors rather than on factors that can change from hearing to hearing, such as noncompliance with court-imposed probation conditions. The current study addressed this gap, using generalized estimating equation analyses with 77 youths' archived public defender files--providing data from 268 review hearings--to evaluate the role of both youth-specific factors (e.g., demographic characteristics) and hearing-specific factors (e.g., noncompliance with imposed probation requirements) in residential facility commitment. Results revealed that youth who were absent from the examined review hearing, were rearrested, failed to comply with school-related probation requirements, or failed to appear as directed at the prior review hearing were more likely to have probation revoked and be placed in a juvenile correctional facility. Such findings might help identify groups of youth at greater risk for facility commitment and might inform the guidance provided to juvenile probationers by their families, attorneys, and probation officers. PMID- 26550680 TI - Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. AB - Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (gammaGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities. PMID- 26550681 TI - Tunable Electromagnetic Coupling in Plasmonic Nanostructures Mediated by Thermoresponsive Polymer Brushes. AB - A smart and highly SERS-active plasmonic platform was designed by coupling regular arrays of nanotriangles to colloidal gold nanorods via a thermoresponsive polymer spacer (poly(N-isopropylacrylamide), PNIPAM). The substrates were prepared by combining a top-down and a bottom-up approach based on nanosphere lithography, surface-initiated controlled radical polymerization, and colloidal assembly. This multistep strategy provided regular hexagonal arrays of nanotriangles functionalized by polymer brushes and colloidal gold nanorods, confined exclusively on the nanotriangle surface. Interestingly, one could finely tune the gold nanorod impregnation on the polymer-coated nanostructures by adjusting the polymer layer thickness, leading to highly coupled plasmonic systems for intense SERS signal. Moreover, the thermoresponsive properties of the PNIPAM brushes could be wisely handled in order to monitor the SERS activity of the nanostructures coupled via this polymer spacer. The coupled hybrid plasmonic nanostructures designed in this work are therefore very promising smart platforms for the sensitive detection of analytes by SERS. PMID- 26550682 TI - A Suite of Tetraphenylethylene-Based Discrete Organoplatinum(II) Metallacycles: Controllable Structure and Stoichiometry, Aggregation-Induced Emission, and Nitroaromatics Sensing. AB - Materials that organize multiple functionally active sites, especially those with aggregation-induced emission (AIE) properties, are of growing interest due to their widespread applications. Despite promising early architectures, the fabrication and preparation of multiple AIEgens, such as multiple tetraphenylethylene (multi-TPE) units, in a single entity remain a big challenge due to the tedious covalent synthetic procedures often accompanying such preparations. Coordination-driven self-assembly is an alternative synthetic methodology with the potential to deliver multi-TPE architectures with light emitting characteristics. Herein, we report the preparation of a new family of discrete multi-TPE metallacycles in which two pendant phenyl rings of the TPE units remain unused as a structural element, representing novel AIE-active metal organic materials based on supramolecular coordination complex platforms. These metallacycles possess relatively high molar absorption coefficients but weak fluorescent emission under dilute conditions because of the ability of the untethered phenyl rings to undergo torsional motion as a non-radiative decay pathway. Upon molecular aggregation, the multi-TPE metallacycles show AIE activity with markedly enhanced quantum yields. Moreover, on account of their AIE characteristics in the condensed state and ability to interact with electron deficient substrates, the photophysics of these metallacycles is sensitive to the presence of nitroaromatics, motivating their use as sensors. This work represents a unification of themes including molecular self-assembly, AIE, and fluorescence sensing and establishes structure-property-application relationships of multi-TPE scaffolds. The fundamental knowledge obtained from the current research facilitates progress in the field of metal-organic materials, metal-coordination induced emission, and fluorescent sensing. PMID- 26550683 TI - Theoretical Study of FH2- Electron Photodetachment Spectra on New Ab Initio Potential Energy Surfaces. AB - The FH2- anion has a stable structure that resembles a configuration in the vicinity of the transition state for neutral reaction F + H2 -> HF + H. Electron photodetachment spectra of the FH2- anion reveal the neutral reaction dynamics in the critical transition-state region. Accurate quantum dynamics simulations of the photodetachment spectra using highly accurate new ab initio potential energy surfaces for both anionic and neutral FH2 are performed and compared with all available experimental results. The results provide reliable interpretations for the experimental observations of FH2- photoelectron detachment and reveal a detailed picture of the molecular dynamics around the transition state of the F + H2 reaction. The latest high-resolution photoelectron detachment spectra [Kim et al. Science, 2015, 349, 510-513] confirm the high accuracy of our new potential energy surface for describing the resonance-enhanced reactivity of the neutral F + H2 reaction. PMID- 26550684 TI - Artificial Avidin-Based Receptors for a Panel of Small Molecules. AB - Proteins with high specificity, affinity, and stability are needed for biomolecular recognition in a plethora of applications. Antibodies are powerful affinity tools, but they may also suffer from limitations such as low stability and high production costs. Avidin and streptavidin provide a promising scaffold for protein engineering, and due to their ultratight binding to D-biotin they are widely used in various biotechnological and biomedical applications. In this study, we demonstrate that the avidin scaffold is suitable for use as a novel receptor for several biologically active small molecules: Artificial, chicken avidin-based proteins, antidins, were generated using a directed evolution method for progesterone, hydrocortisone, testosterone, cholic acid, ketoprofen, and folic acid, all with micromolar to nanomolar affinity and significantly reduced biotin-binding affinity. We also describe the crystal structure of an antidin, sbAvd-2(I117Y), a steroid-binding avidin, which proves that the avidin scaffold can tolerate significant modifications without losing its characteristic tetrameric beta-barrel structure, helping us to further design avidin-based small molecule receptors. PMID- 26550685 TI - Withdrawn: Bone marrow fat and the decline of B lymphopoiesis in rabbits. PMID- 26550686 TI - Diagnosing hypogonadism and treating decisions in different parts of the world: shifts in patterns between 2006 and 2015. AB - AIM: Variations in diagnosing and treating testosterone (T) deficiency between different regions of the world were analyzed in 2006, and repeated in 2010. At present, the changes since 2006 were analyzed. METHODS: About 731 physicians were interviewed in Europe, South Africa, Central and South America regarding factors determining: (1) prescription of T or withholding T, (2) factors in the long-term use of T and the role of T formulations therein, (3) awareness of the wider spectrum of action of T (cardiometabolic disease) (4) reimbursement of T and its impact on (continued) use and (5) best strategies for information on T for physicians. RESULTS: Total T was a key factor in identifying hypogonadism, but for >80% of physicians, clinical symptoms were weighed during diagnosis. Once diagnosed, >85% received T treatment, but the treatment compliance was problematic. Of these patients, 36% decided not to start or continue the treatment. CONCLUSION: More hypogonadal men are treated than before, but ~20% goes unidentified. Physicians have a greater awareness that T deficiency can be an element in cardiovascular and metabolic disease, but more education of physicians on diagnosis and treatment of hypogonadism are needed. Problems with reimbursement of T are barriers in the prescription of T and its use by patients. PMID- 26550688 TI - Cyclopentadiene Construction via Rh-Catalyzed Carbene/Alkyne Metathesis Terminated with Intramolecular Formal [3 + 2] Cycloaddition. AB - A new type of intramolecular carbene cascade reaction of alkynyl-tethered styryl diazoesters is presented, which is terminated with a formal [3 + 2] cycloaddition to give the bicyclic cyclopentadiene derivatives in high yields and selectivity. Additionally, it was found that the beta-H shift is the dominating process in the case of alkyl alkyne-tethered substrates. PMID- 26550687 TI - Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. AB - RATIONALE: Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. OBJECTIVES: To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. METHODS: Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting beta2-agonist fluticasone furoate/vilanterol 100/25 MUg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. MEASUREMENTS AND MAIN RESULTS: There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. CONCLUSIONS: Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885). PMID- 26550691 TI - Corrigendum. PMID- 26550690 TI - C-termini are essential and distinct for nucleic acid binding of human NABP1 and NABP2. AB - BACKGROUND: Human Nucleic Acid Binding Protein 1 and 2 (hNABP1 and 2; also known as hSSB2 and 1, respectively) are two newly identified single-stranded (ss) DNA binding proteins (SSB). Both NABP1 and NABP2 have a conserved oligonucleotide/oligosaccharide-binding (OB)-fold domain and a divergent carboxy terminal domain, the functional importance of which is unknown. METHODS: Recombinant hNABP1/2 proteins were purified using affinity and size exclusion chromatography and their identities confirmed by mass spectrometry. Oligomerization state was checked by sucrose gradient centrifugation. Secondary structure was determined by circular dichroism spectroscopy. Nucleic acid binding ability was examined by EMSA and ITC. RESULTS: Both hNABP1 and hNABP2 exist as monomers in solution; however, hNABP2 exhibits anomalous behavior. CD spectroscopy revealed that the C-terminus of hNABP2 is highly disordered. Deletion of the C-terminal tail diminishes the DNA binding ability and protein stability of hNABP2. Although both hNABP1 and hNABP2 prefer to bind ssDNA than double-stranded (ds) DNA, hNABP1 has a higher affinity for ssDNA than hNABP2. Unlike hNABP2, hNABP1 protein binds and multimerizes on ssDNA with the C-terminal tail responsible for its multimerization. Both hNABP1 and hNABP2 are able to bind single-stranded RNA, with hNABP2 having a higher affinity than hNABP1. CONCLUSIONS: Biochemical evidence suggests that the C-terminal region of NABP1 and NABP2 is essential for their functionality and may lead to different roles in DNA and RNA metabolism. GENERAL SIGNIFICANCE: This is the first report demonstrating the regulation and functional properties of the C-terminal domain of hNABP1/2, which might be a general characteristic of OB-fold proteins. PMID- 26550692 TI - First European Congress on Hereditary ATTR amyloidosis. PMID- 26550693 TI - Mitochondrial dynamics and mitophagy in Parkinson's disease: A fly point of view. AB - Mitochondria are double membrane-bounded organelles residing in the cytoplasm of almost all eukaryotic cells, which convert energy from the disposal of organic substrates into an electrochemical gradient that is in turn converted into ATP. However, the ion gradient that is generated through the oxidation of nutrients, may lead to the production of reactive oxygen species (ROS), which can generate free radicals, damaging cells and contributing to disease. Originally described as static structures, to date they are considered extremely plastic and dynamic organelles. In this respect, mitochondrial dynamics is crucial to prevent potential damage that is generated by ROS. For instance, mitochondria elongate to dilute oxidized proteins into the mitochondrial network, and they fragment to allow selective elimination of dysfunctional mitochondria via mitophagy. Accordingly, mitochondrial dynamics perturbation may compromise the selective elimination of damaged proteins and dysfunctional organelles and lead to the development of different diseases including neurodegenerative diseases. In recent years the fruit fly Drosophila melanogaster has proved to be a valuable model system to evaluate the consequences of mitochondria quality control dysfunction in vivo, particularly with respect to PINK1/Parkin dependent dysregulation of mitophagy in the onset of Parkinson's Disease (PD). The current challenge is to be able to use fly based genetic strategies to gain further insights into molecular mechanisms underlying disease in order to develop new therapeutic strategies. This article is part of a Special Issue entitled: Role of mitochondria in physiological and pathophysiological functions in the central nervous system. PMID- 26550695 TI - Phosphatase activity of Bombyx mori nucleopolyhedrovirus PTP is dispensable for enhanced locomotory activity in B. mori larvae. AB - Baculovirus-induced enhanced locomotory activity (ELA) is not induced in caterpillars infected with a mutant Bombyx mori nucleopolyhedrovirus (BmNPV) or Autographa californica multiple nucleopolyhedrovirus (AcMNPV) lacking a functional protein tyrosine phosphatase gene (ptp). Previous studies suggest that the PTP proteins from BmNPV and AcMNPV act in different ways to induce ELA, i.e., BmNPV PTP is utilized as a virion structural component, whereas AcMNPV PTP requires its phosphatase activity. Here, I generated and characterized two new BmNPV mutants expressing enzymatically inactive PTP proteins and confirmed that the phosphatase activity of PTP is not required for ELA induction in BmNPV infected B. mori larvae. PMID- 26550689 TI - Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. AB - BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (+/-SD) 2-year LVESVI was 52.6+/-27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6+/-39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.). PMID- 26550696 TI - Visual Acuity Outcomes of the Boston Keratoprosthesis Type 1: Multicenter Study Results. AB - PURPOSE: To report logarithm of the minimal angle of resolution (logMAR) visual outcomes of the Boston keratoprosthesis type 1. DESIGN: Prospective cohort study. METHODS: Preoperative, intraoperative, and postoperative parameters of 300 eyes of 300 patients who underwent implantation of a Boston keratoprosthesis type 1 device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers were collected. RESULTS: After an average of 17.1 +/- 14.8 months, visual acuity improved significantly (P < .0001) to a mean final value of 0.89 +/- 0.64 (20/150). There were also significantly fewer eyes with light perception (6.7%; n = 19; P < .0001), although 3.1% (n = 9) progressed to no light perception. There was no association between age (P = .08), sex (P = .959), operative side (P = .167), or failure (P = .494) and final visual acuity. The median time to achieve 20/200 visual acuity was 1 month (95% confidence interval 1.0-6.0) and it was retained for an average of 47.8 months. Multivariate analysis, controlling for preoperative visual acuity, demonstrated 2 factors associated with final visual outcome: chemical injury was associated with better final vision (P = .007), whereas age-related macular degeneration was associated with poorer vision (P < .0001). CONCLUSIONS: The Boston keratoprosthesis type 1 is an effective device for rehabilitation in advanced ocular surface disease, resulting in a significant improvement in visual acuity. Eyes achieved a mean value of 20/150 (0.89 +/- 0.64 logMAR units) after 6 months and this was relatively stable thereafter. The best visual prognosis is observed in chemical injury eyes, whereas the worst prognosis is in aniridia, although the latter has limited visual potential. PMID- 26550697 TI - Relationship between serum uric acid level and cardiometabolic risks in nondiabetic patients with schizophrenia. AB - This study examined the relationship between serum levels of uric acid and insulin resistance and metabolic syndrome in nondiabetic patients with schizophrenia. Outpatients diagnosed with schizophrenia or schizoaffective disorder participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine serum levels of metabolic measures. A total of 135 patients were recruited for the study. A significant positive relationship was found between serum levels of uric acid and the homeostasis model of assessing insulin resistance (log transformed, r=0.394, P<0.001), and a significant negative relationship was found between serum levels of uric acid and low-density lipoprotein particle size (log transformed, r=-0.306, P=0.001) after controlling for potential confounding variables. Hierarchical multiple regression suggested that serum uric acid level is a significant predictor of insulin resistance (P=0.001) and of low-density lipoprotein particle size (P<0.015). Further, logistic regression showed that serum uric acid levels strongly predicted the condition of metabolic syndrome (odds ratio 0.630, 95% confidence interval 0.463-0.856, P=0.003). This study suggested that uric acid may be a clinically useful biomarker to indicate cardiometabolic risks in nondiabetic patients with schizophrenia. PMID- 26550694 TI - Recombinant Slit2 attenuates neuroinflammation after surgical brain injury by inhibiting peripheral immune cell infiltration via Robo1-srGAP1 pathway in a rat model. AB - BACKGROUND AND PURPOSE: Peripheral immune cell infiltration to the brain tissue at the perisurgical site can promote neuroinflammation after surgical brain injury (SBI). Slit2, an extracellular matrix protein, has been reported to reduce leukocyte migration. This study evaluated the effect of recombinant Slit2 and the role of its receptor roundabout1 (Robo1) and its downstream mediator Slit-Robo GTPase activating protein 1 (srGAP1)-Cdc42 on peripheral immune cell infiltration after SBI in a rat model. METHODS: One hundred and fifty-three adult male Sprague Dawley rats (280-350 g) were used. Partial resection of right frontal lobe was performed to induce SBI. Slit2 siRNA was administered by intracerebroventricular injection 24h before SBI. Recombinant Slit2 was injected intraperitoneally 1h before SBI. Recombinant Robo1 used as a decoy receptor was co-administered with recombinant Slit2. srGAP1 siRNA was administered by intracerebroventricular injection 24h before SBI. Post-assessments included brain water content measurement, neurological tests, ELISA, Western blot, immunohistochemistry, and Cdc42 activity assay. RESULTS: Endogenous Slit2 was increased after SBI. Robo1 was expressed by peripheral immune cells. Endogenous Slit2 knockdown worsened brain edema after SBI. Recombinant Slit2 administration reduced brain edema, neurological deficits, and pro-inflammatory cytokines after SBI. Recombinant Slit2 reduced peripheral immune cell markers cluster of differentiation 45 (CD45) and myeloperoxidase (MPO), as well as Cdc42 activity in the perisurgical brain tissue which was reversed by recombinant Robo1 co-administration and srGAP1 siRNA. CONCLUSIONS: Recombinant Slit2 improved outcomes by reducing neuroinflammation after SBI, possibly by decreasing peripheral immune cell infiltration to the perisurgical site through Robo1-srGAP1 mediated inhibition of Cdc42 activity. These results suggest that Slit2 may be beneficial to reduce SBI induced neuroinflammation. PMID- 26550698 TI - [Support in diagnostics and therapy]. AB - There is no proven effective treatment for many diseases today that proves to be one of the greatest problems of health care. Therefore, different therapeutic decisions are made in connection with the same disease by hospitals. There is a growing need for reviews which summarize the information collected from professional literature with scientific methods. The aim of the authors was to show the limitations of conventional narrative reviews, and to present the method and importance of systematic reviews to Hungarian professionals. Systematic reviews are transparent studies which are based on a predetermined protocol and collate all empirical evidence to answer a specific research question, and consequently provide more reliable results. They use explicit and systematic methods to minimize bias, and provide evidence for clinicians and policy makers to help them make diagnostic and therapeutic decisions which are essential in several fields of the health care system and health policy, too. PMID- 26550699 TI - [Lactose intolerance: past and present. Part 1]. AB - Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy. PMID- 26550700 TI - [Applicability of hospital reports submitted for reimbursement purposes for epidemiological studies based on the example of ischemic cerebrovascular diseases]. AB - INTRODUCTION: In single-payer health care financing systems data extracted from hospital report forms submitted for reimbursement purposes may be used for epidemiological investigations. AIM: Based on data submitted by 14 neurological wards in Central Hungary the authors examined the reliability of these reports. METHOD: Analyses were performed for the 3-digit codes of the 10th version of the International Classification of Diseases for cerebral infarcts (ICD-10 I63+I64) reported for the National Health Insurance Fund. RESULTS: The number of cases in individual hospitals changed between a decrease by 35% and an increase by 73% from the first to the second half of the year 2012, reflecting changes in the size of the catchment area of the hospitals in July 2012. Of those with an ICD-10 I63 or I64 discharge diagnosis 54-84% had acute stroke. Neurological wards cared for 34-98% of all stroke patients. The diagnoses submitted for reimbursement purposes corresponded in over 99% to the diagnoses in the hospital discharge reports. Inaccuracies occurred in a larger proportion (about 20%) in coding the DRG financing categories. CONCLUSIONS: Databases created from hospital reports submitted for reimbursement purposes can be used reliably in Hungary for stroke epidemiological studies. PMID- 26550701 TI - [Laparoscopic resection of persistent patent urachus]. AB - The urachus in the foetus is a fibromuscular duct, which connects the allantois to the bladder and it is usually occluded in the 4-5th gestation months. Incomplete occlusion of the urachus at the time of birth is considered to be physiological, but later it can lead to recurrent discharge and inflammation of the umbilicus. To establish the diagnosis, ultrasound is the first examination of choice. A 19-year old obese female patient presented with umbilical discharge, and a persistent urachus was detected by ultrasound. After incision of the peritoneum the duct was excised from the umbilicus to the dome of the bladder by 3-port laparoscopy where the duct was clipped. The operation time was 38 minutes. The patient required minor analgesia on one single occasion in the postoperative period and was discharged on the first postoperative day. The authors recommend laparoscopic operation for the urachal remnant; the enlarged duct on the ventral abdominal wall can be better detected from the umbilicus to the Retzius spatium with 30-degree camera, and the cosmetic outcome is also more favourable. PMID- 26550702 TI - [Beyond the impact factor. Reflections on the book of Stefanie Haustein]. AB - The excellent book on multidimensional journal evaluation by Stefanie Haustein helps to find the place of the impact factor in the complex system of journal evaluation indicators. By delimiting the dimensions of evaluation and the user groups, the author of the book creates a framework that serves as a novel and useful guidance both for the lay reader and the expert. PMID- 26550703 TI - [Amazing stories of cesarean section]. PMID- 26550705 TI - A mathematical model for Crimean-Congo haemorrhagic fever: tick-borne dynamics with conferred host immunity. AB - Crimean-Congo haemorrhagic fever (CCHF) is a highly contagious tick-borne disease that impacts many countries in parts of Africa, Europe, Asia, and the Middle East. Outbreaks are episodic, but deadly. Due to the highly contagious nature of this disease, suspected cases are taken extremely serious, with very strong control measures implemented almost immediately. It is primarily those living on farms, livestock workers, and medical workers who are at risk. The virus responsible for CCHF is transmitted asymptomatically and transiently to livestock, and symptomatically to humans. The fatality rate in human cases can be very high. The number of methods and directions of viral transmission is large, including tick-to-tick, tick-to-livestock, tick-to-human, livestock-to-tick, livestock-to-human, and human-to-human. We model CCHF using a deterministic system of nonlinear differential equations. This compartment model allows us to analyse threshold parameters and equilibria describing the magnitude and progression of cases of the disease in a hypothetical outbreak. PMID- 26550706 TI - An assessment of air quality reflecting the chemosensory irritation impact of mixtures of volatile organic compounds. AB - We present a method to assess the air quality of an environment based on the chemosensory irritation impact of mixtures of volatile organic compounds (VOCs) present in such environment. We begin by approximating the sigmoid function that characterizes psychometric plots of probability of irritation detection (Q) versus VOC vapor concentration to a linear function. First, we apply an established equation that correlates and predicts human sensory irritation thresholds (SIT) (i.e., nasal and eye irritation) based on the transfer of the VOC from the gas phase to biophases, e.g., nasal mucus and tear film. Second, we expand the equation to include other biological data (e.g., odor detection thresholds) and to include further VOCs that act mainly by "specific" effects rather than by transfer (i.e., "physical") effects as defined in the article. Then we show that, for 72 VOCs in common, Q values based on our calculated SITs are consistent with the Threshold Limit Values (TLVs) listed for those same VOCs on the basis of sensory irritation by the American Conference of Governmental Industrial Hygienists (ACGIH). Third, we set two equations to calculate the probability (Qmix) that a given air sample containing a number of VOCs could elicit chemosensory irritation: one equation based on response addition (Qmix scale: 0.00 to 1.00) and the other based on dose addition (1000*Qmix scale: 0 to 2000). We further validate the applicability of our air quality assessment method by showing that both Qmix scales provide values consistent with the expected sensory irritation burden from VOC mixtures present in a wide variety of indoor and outdoor environments as reported on field studies in the literature. These scales take into account both the concentration of VOCs at a particular site and the propensity of the VOCs to evoke sensory irritation. PMID- 26550707 TI - Novel Cadmium Responsive MicroRNAs in Daphnia pulex. AB - Daphnia pulex is a widely used toxicological model and is known for its sensitivity to cadmium (Cd). Recent research suggests that microRNAs (miRNAs) play a critical role in animal responses to heavy metals. To investigate the functions of D. pulex miRNAs under Cd exposure, we analyzed the miRNA profiles of D. pulex after 48 h using miRNA microarrays and validated our findings by q-PCR. miRNA dpu-let-7 was identified as a stably expressed gene and used as a reference. We identified 22 and 21 differentially expressed miRNAs under low (20 MUg/L CdCl2) and high-exposure (40 MUg/L CdCl2) concentrations compared to controls, respectively. Cellular functions of predicted miRNA target Cd responsive genes included oxidative stress, ion transport, mitochondrial damage, and DNA repair. An insulin-related network was also identified in relation to several Cd-responsive miRNAs. The expression of three predicted target genes for miR-71 and miR-210 were evaluated, and expression of two of them (SCN2A and SLC31A1) was negatively correlated with the expression of their regulator miRNAs. We show miR-210 is hypoxia-responsive in D. pulex and propose Cd and hypoxia induce miR-210 via a same HIF1alpha modulated pathway. Collectively, this research advances our understanding on the role of miRNAs in response to heavy metal exposure. PMID- 26550708 TI - Neurodegenerative diseases: From available treatments to prospective herbal therapy. AB - Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and many others represent a relevant health problem with age worldwide. Efforts have been made in recent years to discover the mechanism of neurodegenerative diseases and prospective therapy that can help to slow down the effects of the aging and prevent these diseases. Since pathogenesis of these diseases involves multiple factors therefore the important task for neuroscientists is to identify such multiple factors and prevent age-associated neurodegenerative diseases. For these neurodegenerative diseases yet we have only palliative therapies and none of them significantly capable to slow down or halt the underlying pathology. Polyphenolic compounds such as flavonoids present in vegetables and fruits are believed to have anti-aging properties and reduce the risk of neurodegenerative diseases. Despite their abundance, investigations into the benefits of these polyphenolic compounds in human health have only recently begun. Preclinical and clinical studies have demonstrated the potential beneficial effects of flavonoids in neurons. Although clinical trials on the effectiveness of dietary flavonoids to treat human diseases are limited but various animal models and cell culture studies have shown a great promise in developing these compounds as suitable therapeutic targets. In this review, we elaborate the neuroprotective properties of flavonoids especially their applications in prevention and intervention of different neurodegenerative diseases. Their multi-target properties may allow them to be potential dietary supplement in prevention and treatment of the age associated neurodegenerative diseases. PMID- 26550709 TI - Production of extracellular fructans by Gluconobacter nephelii P1464. AB - Bacterial extracellular fructans, known as levans, have potential applications in food, pharmaceutical and cosmetic industries and high fructan producing strains could contribute into the cost reduction and more extensive commercial usage of them. An acetic acid bacteria (AAB) isolate P1464 was obtained from the Microbial Strain Collection of Institute of Microbiology and Biotechnology, University of Latvia and identified as Gluconobacter nephelii by DNA-DNA hybridization and the formation of extracellular fructans by this strain was confirmed. Isolated extracellular fructose polymers were characterized using FT-IR spectroscopy and the structural features of fructan appeared as similar to the reference sample of bacterial levan. Molecular mass estimates showed that the isolated G. nephelii P1464 fructose polymer has a relatively small molecular weight (Mw 1122.939 +/- 153.453 kDa) and a sizeable polydispersity (Mw/Mn = 21.57 +/- 1.60), as compared with other AAB, which could promote their physiological activity, including the prebiotic effects. Obtained at different cultivation conditions characteristics of fructan production, including the biotechnological indices such as the productivity (Qp) and yield (Yp/s) ranging from 0.774 to 1.244 g l(-1) h and from 0.181 to 0.436 g g(-1) , respectively, confirmed, that G. nephelii P1464 could be used as promising strain for commercial production of levan. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial fructans, known as levans, have extensive options for practical usage, however, actually limited due to high production costs. Therefore, the searches for efficient producer strains should be an urgent task to reduce costs. This study is the first report on the formation of fructans by a novel strain of acetic acid bacteria (AAB) Gluconobacter nephelii P1464. Characteristics obtained at different cultivation conditions confirmed the operation of a competitive and perspective producer strain. Isolated extracellular fructans are characterized by a lower molecular weight as compared with other AAB which could promote their physiological activity, including the prebiotic effects. PMID- 26550710 TI - Necessary and Sufficient Conditions for an Extended Noncontextuality in a Broad Class of Quantum Mechanical Systems. AB - The notion of (non)contextuality pertains to sets of properties measured one subset (context) at a time. We extend this notion to include so-called inconsistently connected systems, in which the measurements of a given property in different contexts may have different distributions, due to contextual biases in experimental design or physical interactions (signaling): a system of measurements has a maximally noncontextual description if they can be imposed a joint distribution on in which the measurements of any one property in different contexts are equal to each other with the maximal probability allowed by their different distributions. We derive necessary and sufficient conditions for the existence of such a description in a broad class of systems including Klyachko Can-Binicioglu-Shumvosky-type (KCBS), EPR-Bell-type, and Leggett-Garg-type systems. Because these conditions allow for inconsistent connectedness, they are applicable to real experiments. We illustrate this by analyzing an experiment by Lapkiewicz and colleagues aimed at testing contextuality in a KCBS-type system. PMID- 26550711 TI - Stochastic Independence as a Resource in Small-Scale Thermodynamics. AB - It is well known in thermodynamics that the creation of correlations costs work. It seems then a truism that if a thermodynamic transformation A->B is impossible, so will be any transformation that in sending A to B also correlates among them some auxiliary systems C. Surprisingly, we show that this is not the case for nonequilibrium thermodynamics of microscopic systems. On the contrary, the creation of correlations greatly extends the set of accessible states, to the point that we can perform on individual systems and in a single shot any transformation that would otherwise be possible only if the number of systems involved was very large. We also show that one only ever needs to create a vanishingly small amount of correlations (as measured by mutual information) among a small number of auxiliary systems (never more than three). The many, severe constraints of microscopic thermodynamics are reduced to the sole requirement that the nonequilibrium free energy decreases in the transformation. This shows that, in principle, reliable extraction of work equal to the free energy of a system can be performed by microscopic engines. PMID- 26550712 TI - Secrecy in Prepare-and-Measure Clauser-Horne-Shimony-Holt Tests with a Qubit Bound. AB - The security of device-independent (DI) quantum key distribution (QKD) protocols relies on the violation of Bell inequalities. As such, their security can be established based on minimal assumptions about the devices, but their implementation necessarily requires the distribution of entangled states. In a setting with fully trusted devices, any entanglement-based protocol is essentially equivalent to a corresponding prepare-and-measure protocol. This correspondence, however, is not generally valid in the DI setting unless one makes extra assumptions about the devices. Here we prove that a known tight lower bound on the min entropy in terms of the Clauser-Horne-Shimony-Holt Bell correlator, which has featured in a number of entanglement-based DI QKD security proofs, also holds in a prepare-and-measure setting, subject only to the assumption that the source is limited to a two-dimensional Hilbert space. PMID- 26550713 TI - Operational Multipartite Entanglement Measures. AB - We introduce two operational entanglement measures that are applicable for arbitrary multipartite (pure or mixed) states. One of them characterizes the potentiality of a state to generate other states via local operations assisted by classical communication and the other characterizes the simplicity of generating the state at hand. We show how these measures can be generalized to two classes of entanglement measures. Moreover, we compute the new measures for pure few partite systems and use them to characterize the entanglement contained in a three-qubit state. We identify the Greenberger-Horne-Zeilinger and W state as the most powerful pure three-qubit states regarding state manipulation. PMID- 26550714 TI - Remote Entanglement by Coherent Multiplication of Concurrent Quantum Signals. AB - Concurrent remote entanglement of distant, noninteracting quantum entities is a crucial function for quantum information processing. In contrast with the existing protocols which employ the addition of signals to generate entanglement between two remote qubits, the continuous variable protocol we present is based on the multiplication of signals. This protocol can be straightforwardly implemented by a novel Josephson junction mixing circuit. Our scheme would be able to generate provable entanglement even in the presence of practical imperfections: finite quantum efficiency of detectors and undesired photon loss in current state-of-the-art devices. PMID- 26550715 TI - Bulk-Boundary Duality, Gauge Invariance, and Quantum Error Corrections. AB - Recently, Almheiri, Dong, and Harlow have argued that the localization of bulk information in a boundary dual should be understood in terms of quantum error correction. We show that this structure appears naturally when the gauge invariance of the boundary theory is incorporated. This provides a new understanding of the nonuniqueness of the bulk fields (precursors). It suggests a close connection between gauge invariance and the emergence of spacetime. PMID- 26550717 TI - B->pill Form Factors for New Physics Searches from Lattice QCD. AB - The rare decay B->pil^{+}l^{-} arises from b->d flavor-changing neutral currents and could be sensitive to physics beyond the standard model. Here, we present the first ab initio QCD calculation of the B->pi tensor form factor f_{T}. Together with the vector and scalar form factors f_{+} and f_{0} from our companion work [J. A. Bailey et al., Phys. Rev. D 92, 014024 (2015)], these parametrize the hadronic contribution to B->pi semileptonic decays in any extension of the standard model. We obtain the total branching ratio BR(B^{+}->pi^{+}MU^{+}MU^{ })=20.4(2.1)*10^{-9} in the standard model, which is the most precise theoretical determination to date, and agrees with the recent measurement from the LHCb experiment [R. Aaij et al., J. High Energy Phys. 12 (2012) 125]. PMID- 26550716 TI - Polarization Transfer in Wide-Angle Compton Scattering and Single-Pion Photoproduction from the Proton. AB - Wide-angle exclusive Compton scattering and single-pion photoproduction from the proton have been investigated via measurement of the polarization transfer from a circularly polarized photon beam to the recoil proton. The wide-angle Compton scattering polarization transfer was analyzed at an incident photon energy of 3.7 GeV at a proton scattering angle of theta_{cm}^{p}=70 degrees . The longitudinal transfer K_{LL}, measured to be 0.645+/-0.059+/-0.048, where the first error is statistical and the second is systematic, has the same sign as predicted for the reaction mechanism in which the photon interacts with a single quark carrying the spin of the proton. However, the observed value is ~3 times larger than predicted by the generalized-parton-distribution-based calculations, which indicates a significant unknown contribution to the scattering amplitude. PMID- 26550719 TI - Generating Isolated Elliptically Polarized Attosecond Pulses Using Bichromatic Counterrotating Circularly Polarized Laser Fields. AB - We theoretically demonstrate the possibility to generate both trains and isolated attosecond pulses with high ellipticity in a practical experimental setup. The scheme uses circularly polarized, counterrotating two-color driving pulses carried at the fundamental and its second harmonic. Using a model Ne atom, we numerically show that highly elliptic attosecond pulses are generated already at the single-atom level. Isolated pulses are produced by using few-cycle drivers with controlled time delay between them. PMID- 26550720 TI - Virtual Sequential Picture for Nonsequential Two-Photon Double Ionization of Helium. AB - By using a model based on the second-order time-dependent perturbation theory, we show that the nonsequential two-photon double ionization of He can be understood in a virtual sequential picture: to excite the final double continuum state |k_{1},k_{2}? by absorbing two photons from the ground state |1s^{2},^{1}S_{0}?, the single continuum states |1s,k_{1}? and |1s,k_{2}? serve as the dominant intermediate states. This virtual sequential picture is verified by the perfect agreement of the total ionization cross section, respectively, calculated by this model and by the sophisticated numerical solution to the full-dimensional time dependent Schrodinger equation. This model, without the consideration of the electron correlation in the final double continuum state, works well for a wide range of laser parameters extending from the nonsequential to the sequential regime. The present Letter demonstrates that the electron correlation in the final double continuum state is not important in evaluating the total cross section, while it is indispensable for an accurate computation of a triply differential cross section. In addition, the virtual sequential picture bridges the sequential and nonsequential two-photon double ionization and reveals connections and distinctions between them. PMID- 26550721 TI - Geometric Phase Appears in the Ultracold Hydrogen Exchange Reaction. AB - Quantum reactive scattering calculations for the hydrogen exchange reaction H+H_{2}(v=4,j=0)->H+H_{2}(v^{'}, j^{'}) and its isotopic analogues are reported for ultracold collision energies. Because of the unique properties associated with ultracold collisions, it is shown that the geometric phase effectively controls the reactivity. The rotationally resolved rate coefficients computed with and without the geometric phase are shown to differ by up to 4 orders of magnitude. The effect is also significant in the vibrationally resolved and total rate coefficients. The dynamical origin of the effect is discussed and the large geometric phase effect reported here might be exploited to control the reactivity through the application of external fields or by the selection of a particular nuclear spin state. PMID- 26550722 TI - Polarization Engineering in Photonic Crystal Waveguides for Spin-Photon Entanglers. AB - By performing a full analysis of the projected local density of states (LDOS) in a photonic crystal waveguide, we show that phase plays a crucial role in the symmetry of the light-matter interaction. By considering a quantum dot (QD) spin coupled to a photonic crystal waveguide (PCW) mode, we demonstrate that the light matter interaction can be asymmetric, leading to unidirectional emission and a deterministic entangled photon source. Further we show that understanding the phase associated with both the LDOS and the QD spin is essential for a range of devices that can be realized with a QD in a PCW. We also show how suppression of quantum interference prevents dipole induced reflection in the waveguide, and highlight a fundamental breakdown of the semiclassical dipole approximation for describing light-matter interactions in these spin dependent systems. PMID- 26550723 TI - One-Wave Optical Phase Conjugation Mirror by Actively Coupling Arbitrary Light Fields into a Single-Mode Reflector. AB - Rewinding the arrow of time via phase conjugation is an intriguing phenomenon made possible by the wave property of light. Here, we demonstrate the realization of a one-wave optical phase conjugation mirror using a spatial light modulator. An adaptable single-mode filter is created, and a phase-conjugate beam is then prepared by reverse propagation through this filter. Our method is simple, alignment free, and fast while allowing high power throughput in the time reversed wave, which has not been simultaneously demonstrated before. Using our method, we demonstrate high throughput full-field light delivery through highly scattering biological tissue and multimode fibers, even for quantum dot fluorescence. PMID- 26550724 TI - Why Hexagonal Basalt Columns? AB - Basalt columns with their preferably hexagonal cross sections are a fascinating example of pattern formation by crack propagation. Junctions of three propagating crack faces rearrange such that the initial right angles between them tend to approach 120 degrees , which enables the cracks to form a pattern of regular hexagons. To promote understanding of the path on which the ideal configuration can be reached, two periodically repeatable models are presented here involving linear elastic fracture mechanics and applying the principle of maximum energy release rate. They describe the evolution of the crack pattern as a transition from rectangular start configuration to the hexagonal pattern. This is done analytically and by means of three-dimensional finite element simulation. The latter technique reproduces the curved crack path involved in this transition. PMID- 26550725 TI - Logarithmic Mean Temperature Profiles and Their Connection to Plume Emissions in Turbulent Rayleigh-Benard Convection. AB - Two-dimensional simulations of Rayleigh-Benard convection at Ra=5*10^{10} show that vertical logarithmic mean temperature profiles can be observed in regions of the boundary layer where thermal plumes are emitted. The profile is logarithmic only in these regions and not in the rest of the boundary layer where it is sheared by the large-scale wind and impacted by plumes. In addition, the logarithmic behavior is not visible in the horizontal average. The findings reveal that the temperature profiles are strongly connected to thermal plume emission, and they support a perception that parts of the boundary layer can be turbulent while others are not. The transition to the ultimate regime, in which the boundary layers are considered to be fully turbulent, can therefore be understood as a gradual increase in the fraction of the plume-emitting ("turbulent") regions of the boundary layer. PMID- 26550726 TI - Comparative Experimental Study of Fixed Temperature and Fixed Heat Flux Boundary Conditions in Turbulent Thermal Convection. AB - We report the first experimental study of the influences of the thermal boundary condition on turbulent thermal convection. Two configurations were examined: one had a constant heat flux at the bottom boundary and a constant temperature at the top (CFCT cell); the other had constant temperatures at both boundaries (CTCT cell). In addition to producing different temperature stability in the boundary layers, the differences in the boundary condition lead to rather unexpected changes in the flow dynamics. It is found that, surprisingly, reversals of the large-scale circulation occur more frequently in the CTCT cell than in the CFCT cell, despite the fact that in the former its flow strength is on average 9% larger than that in the latter. Our results not only show which aspects of the thermal boundary condition are important in thermal turbulence, but also reveal that, counterintuitively, the stability of the flow is not directly coupled to its strength. PMID- 26550727 TI - Squaring the Circle: Geometric Skewness and Symmetry Breaking for Passive Scalar Transport in Ducts and Pipes. AB - We study the role geometry plays in the emergence of asymmetries in diffusing passive scalars advected by pressure-driven flows in ducts and pipes of different aspect ratios. We uncover nonintuitive, multi-time-scale behavior gauged by a new statistic, which we term "geometric skewness" S^{G}, which measures instantaneously forming asymmetries at short times due to flow geometry. This signature distinguishes elliptical pipes of any aspect ratio, for which S^{G}=0, from rectangular ducts whose S^{G} is generically nonzero, and, interestingly, shows that a special duct of aspect ratio ~0.53335 behaves like a circular pipe as its geometric skewness vanishes. Using a combination of exact solutions, novel short-time asymptotics, and Monte Carlo simulations, we establish the relevant time scales for plateaus and extrema in the evolution of the skewness and kurtosis for our class of geometries. For ducts limiting to channel geometries, we present new exact, single-series formulas for the first four moments on slices used to benchmark Monte Carlo simulations. PMID- 26550728 TI - Wetting Driven by Thermal Fluctuations on Terraced Nanostructures. AB - Theoretical analysis and fully atomistic molecular dynamics simulations reveal a Brownian ratchet mechanism by which thermal fluctuations drive the net displacement of immiscible liquids confined in channels or pores with micro- or nanoscale dimensions. The thermally driven displacement is induced by surface nanostructures with directional asymmetry and can occur against the direction of action of wetting or capillary forces. Mean displacement rates in molecular dynamics simulations are predicted via analytical solution of a Smoluchowski diffusion equation for the position probability density. The proposed physical mechanisms and derived analytical expressions can be applied to engineer surface nanostructures for controlling the dynamics of diverse wetting processes such as capillary filling, wicking, and imbibition in micro- or nanoscale systems. PMID- 26550729 TI - Nonresonant Charged-Particle Acceleration by Electrostatic Waves Propagating across Fluctuating Magnetic Field. AB - In this Letter, we demonstrate the effect of nonresonant charged-particle acceleration by an electrostatic wave propagating across the background magnetic field. We show that in the absence of resonance (i.e., when particle velocities are much smaller than the wave phase velocity) particles can be accelerated by electrostatic waves provided that the adiabaticity of particle motion is destroyed by magnetic field fluctuations. Thus, in a system with stochastic particle dynamics the electrostatic wave should be damped even in the absence of Landau resonance. The proposed mechanism is responsible for the acceleration of particles that cannot be accelerated via resonant wave-particle interactions. Simplicity of this straightforward acceleration scenario indicates a wide range of possible applications. PMID- 26550730 TI - Electron Rephasing in a Laser-Wakefield Accelerator. AB - An important limit for energy gain in laser-plasma wakefield accelerators is the dephasing length, after which the electron beam reaches the decelerating region of the wakefield and starts to decelerate. Here, we propose to manipulate the phase of the electron beam in the wakefield, in order to bring the beam back into the accelerating region, hence increasing the final beam energy. This rephasing is operated by placing an upward density step in the beam path. In a first experiment, we demonstrate the principle of this technique using a large energy spread electron beam. Then, we show that it can be used to increase the energy of monoenergetic electron beams by more than 50%. PMID- 26550731 TI - Quantum Dynamics with Spatiotemporal Control of Interactions in a Stable Bose Einstein Condensate. AB - Optical control of atomic interactions in quantum gases is a long-sought goal of cold atom research. Previous experiments have been hindered by rapid decay of the quantum gas and parasitic deformation of the trap potential. We develop and implement a generic scheme for optical control of Feshbach resonances which yields long quantum gas lifetimes and a negligible parasitic dipole force. We show that fast and local control of interactions leads to intriguing quantum dynamics in new regimes, highlighted by the formation of van der Waals molecules and localized collapse of a Bose condensate. PMID- 26550732 TI - Quantum Mechanical Stabilization of a Collapsing Bose-Bose Mixture. AB - According to the mean-field theory a condensed Bose-Bose mixture collapses when the interspecies attraction becomes stronger than the geometrical average of the intraspecies repulsions, g_{12}^{2}>g_{11}g_{22}. We show that instead of collapsing such a mixture gets into a dilute liquidlike droplet state stabilized by quantum fluctuations thus providing a direct manifestation of beyond mean field effects. We study various properties of the droplet and find, in particular, that in a wide range of parameters its excitation spectrum lies entirely above the particle emission threshold. The droplet thus automatically evaporates itself to zero temperature, the property potentially interesting by itself and from the viewpoint of sympathetic cooling of other systems. PMID- 26550733 TI - Dissipation of Quasiclassical Turbulence in Superfluid ^{4}He. AB - We compare the decay of turbulence in superfluid ^{4}He produced by a moving grid to the decay of turbulence created by either impulsive spin-down to rest or by intense ion injection. In all cases, the vortex line density L decays at late time t as L?t^{-3/2}. At temperatures above 0.8 K, all methods result in the same rate of decay. Below 0.8 K, the spin-down turbulence maintains initial rotation and decays slower than grid turbulence and ion-jet turbulence. This may be due to a decoupling of the large-scale superfluid flow from the normal component at low temperatures, which changes its effective boundary condition from no-slip to slip. PMID- 26550734 TI - Spinor Condensates on a Cylindrical Surface in Synthetic Gauge Fields. AB - We show that by modifying the setup of the recent experiment that creates a "Dirac string" one can engineer a quasi-2D spinor Bose-Einstein condensate on a cylindrical surface, with a synthetic magnetic field normal to the surface. Because of the muticonnectivity of the surface, there are two types of vortices (called A and B) with the same vorticity. This is very different from the planar case, which only has one kind of vortex for fixed circulation. As the strength of the synthetic gauge field increases, the ground states will form a necklace of alternating AB vortices surrounding the lateral midpoint of the cylinder, and will split into two A and B necklaces at higher synthetic gauge fields. The fact that even the basic vortex structure of a Bose-Einstein condensate is altered in a cylindrical surface implies that richer phenomena are in store for quantum gases in other curved surfaces. PMID- 26550735 TI - Maximizing the Strength of Fiber Bundles under Uniform Loading. AB - The collective strength of a system of fibers, each having a failure threshold drawn randomly from a distribution, indicates the maximum load carrying capacity of different disordered systems ranging from disordered solids, power-grid networks, to traffic in a parallel system of roads. In many of the cases where the redistribution of load following a local failure can be controlled, it is a natural requirement to find the most efficient redistribution scheme, i.e., following which system can carry the maximum load. We address the question here and find that the answer depends on the mode of loading. We analytically find the maximum strength and corresponding redistribution schemes for sudden and quasistatic loading. The associated phase transition from partial to total failure by increasing the load has been studied. The universality class is found to be dependent on the redistribution mechanism. PMID- 26550736 TI - Phase Diagram of Pyrochlore Iridates: All-in-All-out Magnetic Ordering and Non Fermi-Liquid Properties. AB - We study the prototype 5d pyrochlore iridate Y_{2}Ir_{2}O_{7} from first principles using the local density approximation and dynamical mean-field theory (LDA+DMFT). We map out the phase diagram in the space of temperature, on-site Coulomb repulsion U, and filling. Consistent with experiments, we find that an all-in-all-out ordered insulating phase is stable for realistic values of U. The trigonal crystal field enhances the hybridization between the j_{eff}=1/2 and j_{eff}=3/2 states, and strong interband correlations are induced by the Coulomb interaction, which indicates that a three-band description is important. We demonstrate a substantial band narrowing in the paramagnetic metallic phase and non-Fermi-liquid behavior in the electron- or hole-doped system originating from long-lived quasi-spin-moments induced by nearly flat bands. PMID- 26550737 TI - Localized Majorana-Like Modes in a Number-Conserving Setting: An Exactly Solvable Model. AB - In this Letter we present, in a number conserving framework, a model of interacting fermions in a two-wire geometry supporting nonlocal zero-energy Majorana-like edge excitations. The model has an exactly solvable line, on varying the density of fermions, described by a topologically nontrivial ground state wave function. Away from the exactly solvable line we study the system by means of the numerical density matrix renormalization group. We characterize its topological properties through the explicit calculation of a degenerate entanglement spectrum and of the braiding operators which are exponentially localized at the edges. Furthermore, we establish the presence of a gap in its single particle spectrum while the Hamiltonian is gapless, and compute the correlations between the edge modes as well as the superfluid correlations. The topological phase covers a sizable portion of the phase diagram, the solvable line being one of its boundaries. PMID- 26550738 TI - Spin-Orbital Excitation Continuum and Anomalous Electron-Phonon Interaction in the Mott Insulator LaTiO_{3}. AB - Raman scattering experiments on stoichiometric, Mott-insulating LaTiO_{3} over a wide range of excitation energies reveal a broad electronic continuum which is featureless in the paramagnetic state, but develops a gap of ~800 cm^{-1} upon cooling below the Neel temperature T_{N}=146 K. In the antiferromagnetic state, the spectral weight below the gap is transferred to well-defined spectral features due to spin and orbital excitations. Low-energy phonons exhibit pronounced Fano anomalies indicative of strong interaction with the electron system for T>T_{N}, but become sharp and symmetric for T=H^{*}?25 T. PMID- 26550746 TI - Nonrelativistic Dynamics of the Amplitude (Higgs) Mode in Superconductors. AB - Despite the formal analogy with the Higgs particle, the amplitude fluctuations of the order parameter in weakly coupled superconductors do not identify a real mode with a Lorentz-invariant dynamics. Indeed, its resonance occurs at 2Delta_{0}, which coincides with the threshold 2E_{gap} for quasiparticle excitations that spoil any relativistic dynamics. Here we investigate the fate of the Higgs mode in the unconventional case where 2E_{gap} becomes larger than 2Delta_{0}, as due to strong coupling or strong disorder. We show that also in this situation, the amplitude fluctuations never identify a real mode at 2Delta_{0}, since such a "bosonic" limit is always reached via strong mixing with the phase fluctuations, which dominate the low-energy part of the spectrum. Our results have direct implications for the interpretation of the subgap optical absorption in disordered superconductors. PMID- 26550748 TI - Spin Nematics, Valence-Bond Solids, and Spin Liquids in SO(N) Quantum Spin Models on the Triangular Lattice. AB - We introduce a simple model of SO(N) spins with two-site interactions which is amenable to quantum Monte Carlo studies without a sign problem on nonbipartite lattices. We present numerical results for this model on the two-dimensional triangular lattice where we find evidence for a spin nematic at small N, a valence-bond solid at large N, and a quantum spin liquid at intermediate N. By the introduction of a sign-free four-site interaction, we uncover a rich phase diagram with evidence for both first-order and exotic continuous phase transitions. PMID- 26550747 TI - Complete Generalized Gibbs Ensembles in an Interacting Theory. AB - In integrable many-particle systems, it is widely believed that the stationary state reached at late times after a quantum quench can be described by a generalized Gibbs ensemble (GGE) constructed from their extensive number of conserved charges. A crucial issue is then to identify a complete set of these charges, enabling the GGE to provide exact steady-state predictions. Here we solve this long-standing problem for the case of the spin-1/2 Heisenberg chain by explicitly constructing a GGE which uniquely fixes the macrostate describing the stationary behavior after a general quantum quench. A crucial ingredient in our method, which readily generalizes to other integrable models, are recently discovered quasilocal charges. As a test, we reproduce the exact postquench steady state of the Neel quench problem obtained previously by means of the Quench Action method. PMID- 26550749 TI - Rayleigh-Jeans Condensation of Pumped Magnons in Thin-Film Ferromagnets. AB - We show that the formation of a magnon condensate in thin ferromagnetic films can be explained within the framework of a classical stochastic non-Markovian Landau Lifshitz-Gilbert equation where the properties of the random magnetic field and the dissipation are determined by the underlying phonon dynamics. We have numerically solved this equation for a tangentially magnetized yttrium-iron garnet film in the presence of a parallel parametric pumping field. We obtain a complete description of all stages of the nonequilibrium time evolution of the magnon gas which is in excellent agreement with experiments. Our calculation proves that the experimentally observed condensation of magnons in yttrium-iron garnet at room temperature is a purely classical phenomenon which should be called Rayleigh-Jeans rather than Bose-Einstein condensation. PMID- 26550750 TI - Long-Range Phase Coherence in Double-Barrier Magnetic Tunnel Junctions with a Large Thick Metallic Quantum Well. AB - Double-barrier heterostructures are model systems for the study of electron tunneling and discrete energy levels in a quantum well (QW). Until now resonant tunneling phenomena in metallic QWs have been observed for limited thicknesses (1 2 nm) under which electron phase coherence is conserved. In the present study we show evidence of QW resonance states in Fe QWs up to 12 nm thick and at room temperature in fully epitaxial double MgAlO_{x} barrier magnetic tunnel junctions. The electron phase coherence displayed in this QW is of unprecedented quality because of a homogenous interface phase shift due to the small lattice mismatch at the Fe-MgAlO_{x} interface. The physical understanding of the critical role of interface strain on QW phase coherence will greatly promote the development of spin-dependent quantum resonant tunneling applications. PMID- 26550751 TI - Electric-Field Control of the Orbital Occupancy and Magnetic Moment of a Transition-Metal Oxide. AB - By using soft-x-ray linear and magnetic dichroism on La_{0.825}Sr_{0.175}MnO_{3}/PbZr_{0.2}Ti_{0.8}O_{3} ferromagnetic-ferroelectric heterostructures we demonstrate a nonvolatile modulation of the Mn 3d orbital anisotropy and magnetic moment. X-ray absorption spectroscopy at the Mn L_{2,3} edges shows that the ferroelectric polarization direction modifies the carrier density, the spin moment, and the orbital splitting of t_{2g} and e_{g} Mn 3d states. These results are consistent with polar distortions of the oxygen octahedra surrounding the Mn ions induced by the switching of the ferroelectric polarization. PMID- 26550752 TI - Dynamical Fano-Like Interference between Rabi Oscillations and Coherent Phonons in a Semiconductor Microcavity System. AB - We report on dynamical interference between short-lived Rabi oscillations and long-lived coherent phonons in CuCl semiconductor microcavities resulting from the coupling between the two oscillations. The Fourier-transformed spectra of the time-domain signals obtained from semiconductor microcavities by using a pump probe technique show that the intensity of the coherent longitudinal optical phonon of CuCl is enhanced by increasing that of the Rabi oscillation, which indicates that the coherent phonon is driven by the Rabi oscillation through the Frohlich interaction. Moreover, as the Rabi oscillation frequency decreases upon crossing the phonon frequency, the spectral profile of the coherent phonon changes from a peak to a dip with an asymmetric structure. The continuous wavelet transformation reveals that these peak and dip structures originate from constructive and destructive interference between Rabi oscillations and coherent phonons, respectively. We demonstrate that the asymmetric spectral structures in relation to the frequency detuning are well reproduced by using a classical coupled oscillator model on the basis of dynamical Fano-like interference. PMID- 26550753 TI - Effective Wall Friction in Wall-Bounded 3D Dense Granular Flows. AB - We report numerical simulations on granular shear flows confined between two flat but frictional sidewalls. Novel regimes differing by their strain localization features are observed. They originate from the competition between dissipation at the sidewalls and dissipation in the bulk of the flow. The effective friction at sidewalls is characterized (effective friction coefficient and orientation of the friction force) for each regime, and its interdependence with slip and force fluctuations is pointed out. We propose a simple scaling law linking the slip velocity to the granular temperature in the main flow direction which leads naturally to another scaling law for the effective friction. PMID- 26550754 TI - Noise-Induced Mechanism for Biological Homochirality of Early Life Self Replicators. AB - The observed single-handedness of biological amino acids and sugars has long been attributed to autocatalysis. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here, we present a theory for a stochastic individual-level model of autocatalysis due to early life self-replicators. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states, in both well-mixed and spatially extended systems. We conclude that autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition. PMID- 26550755 TI - Constant Stress and Pressure Rheology of Colloidal Suspensions. AB - We study the constant stress and pressure rheology of dense hard-sphere colloidal suspensions using Brownian dynamics simulation. Expressing the flow behavior in terms of the friction coefficient-the ratio of shear to normal stress-reveals a shear arrest point from the collapse of the rheological data in the non-Brownian limit. The flow curves agree quantitatively (when scaled) with the experiments of Boyer et al. [Phys. Rev. Lett. 107, 188301 (2011)]. Near suspension arrest, both the shear and the incremental normal viscosities display a universal power law divergence. This work shows the important role of jamming on the arrest of colloidal suspensions and illustrates the care needed when conducting and analyzing experiments and simulations near the flow-arrest transition. PMID- 26550756 TI - Tracer Shape and Local Media Structure Determine the Trend of Translation Rotation Decoupling in Two-Dimensional Colloids. AB - The translational diffusion of tracers in glass-forming materials often violates the Stokes-Einstein relation while their rotation follows the Debye-Stokes Einstein relation faithfully, thus decoupling translational and rotational diffusion. In this Letter, we show by performing molecular dynamics simulations for two-dimensional (2D) colloids that the tracer shape and the local media structure are critical such that rotational diffusion is either suppressed or enhanced depending on the tracer shape. For square tracers dissimilar in structure to the local media structure of 2D colloids, the translation-rotation decoupling occurs and the rotational diffusion is enhanced relative to the translation. For sufficiently large diamond tracers similar in structure to the local media structure, tracers undergo rotational hopping motions and their rotation is suppressed relative to the translation. For distorted-diamond tracers, the decoupling is marginal. Translational diffusion does not change significantly with the tracer shape and obeys the Stokes-Einstein relation. PMID- 26550757 TI - Controlling Chirality of Entropic Crystals. AB - Colloidal crystal structures with complexity and diversity rivaling atomic and molecular crystals have been predicted and obtained for hard particles by entropy maximization. However, thus far homochiral colloidal crystals, which are candidates for photonic metamaterials, are absent. Using Monte Carlo simulations we show that chiral polyhedra exhibiting weak directional entropic forces self assemble either an achiral crystal or a chiral crystal with limited control over the crystal handedness. Building blocks with stronger faceting exhibit higher selectivity and assemble a chiral crystal with handedness uniquely determined by the particle chirality. Tuning the strength of directional entropic forces by means of particle rounding or the use of depletants allows for reconfiguration between achiral and homochiral crystals. We rationalize our findings by quantifying the chirality strength of each particle, both from particle geometry and potential of mean force and torque diagrams. PMID- 26550758 TI - Publisher's Note: Measurement of the Ratio of Branching Fractions B(B[over -]^{0} >D^{*+}tau^{-}nu[over -]_{tau})/B(B[over -]^{0}->D^{*+}MU^{-}nu[over -]_{MU}) [Phys. Rev. Lett. 115, 111803 (2015)]. PMID- 26550718 TI - Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element V_{tb}. AB - We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb^{-1} per experiment. The t-channel cross section is measured to be sigma_{t}=2.25_{-0.31}^{+0.29} pb. We also present the combinations of the two dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s+t channel cross section measurement resulting in sigma_{s+t}=3.30_{-0.40}^{+0.52} pb, without assuming the standard model value for the ratio sigma_{s}/sigma_{t}. The resulting value of the magnitude of the top-to-bottom quark coupling is |V_{tb}|=1.02_{-0.05}^{+0.06}, corresponding to |V_{tb}|>0.92 at the 95% C.L. PMID- 26550759 TI - Publisher's Note: Magnetoanisotropic Andreev Reflection in Ferromagnet Superconductor Junctions [Phys. Rev. Lett. 115, 116601 (2015)]. PMID- 26550760 TI - Publisher's Note: Impurities in Bose-Einstein Condensates: From Polaron to Soliton [Phys. Rev. Lett. 115, 135305 (2015)]. PMID- 26550761 TI - Depression among older adults in Greece: an undetected disorder? PMID- 26550762 TI - In vitro dose and duration dependent approaches for the assessment of ameliorative effects of nanoconjugated vancomycin against Staphylococcus aureus infection induced oxidative stress in murine peritoneal macrophages. AB - AIMS: The present study was aimed to evaluate the in vitro ameliorative effect of nanoconjugated vancomycin (NV) against vancomycin sensitive and resistant strains of Staphylococcus aureus infection-induced oxidative stress in murine peritoneal macrophage. METHODS: Peritoneal macrophages from mice were treated with VSSA and VRSA (5 * 10(6) CFU/mL), VSSA + NV (5-250 MUg/ml) and VRSA + NV (5-250 MUg/ml) for 18 h, having 3 h interval in culture media; and the superoxide anion generation, lipid peroxidation, protein oxidation, antioxidant enzymes status and glutathione enzymes activity were monitored. RESULTS: The significantly increased free radical generation, lipid peroxidation, protein carbonyls and oxidized glutathione levels were observed in VSSA and VRSA treated group as compared to control group; where as reduced glutathione level, antioxidant enzymes status and glutathione dependent enzymes were decreased significantly. All these changes come near to control in NV treated group in a dose and duration dependent fashion. Among the different doses and duration intervals of NV, maximum ameliorative effect was observed by 100 MUg/ml for 12 h treatment which does not produce any damage to the cell. CONCLUSIONS: These findings suggest the potential use and beneficial role of nanoconjugated vancomycin as a modulator of S. aureus infection-induced cellular damage in murine peritoneal macrophage. PMID- 26550763 TI - In-depth snapshot of the equine subgingival microbiome. AB - This study explored the range of bacterial taxa present within healthy subgingival (below the gum-line) niches in the horse oral cavity using 16S rRNA gene amplicon pyrosequencing. Pooled subgingival plaque samples were collected from approximately 200 sulcus sites from two horses (EQ1, EQ2) for analysis. A total of 14,260 quality-filtered pyrosequencing reads were obtained, which were assigned to 3875 operational taxonomic units (OTUs; 99% identity cut-off); 1907 OTUs for EQ1 and 2156 OTUs for EQ2. Diverse taxa from 12 phyla were identified, including Actinobacteria (3.17%), Bacteroidetes (25.11%), Chloroflexi (0.04%), Firmicutes (27.57%), Fusobacteria (5.15%), Proteobacteria (37.67%), Spirochaetes (0.15%), Synergistetes (0.22%), Tenericutes (0.16%), GN02 (0.19%), SR1 (0.01%) and TM7 (0.37%). Many OTUs were not closely related to known phylotypes, and may represent 'equine-specific' taxa. Phylotypes corresponding to Gammaproteobacteria were abundant, including Actinobacillus spp. (8.75%), unclassified Pasteurellaceae (9.90%) and Moraxella spp. (9.58%). PCR targeting the Synergistetes and Spirochaetes phyla was performed, and resultant plasmid libraries of 16S rRNA gene amplicons (ca. 1480 bp) were Sanger sequenced. Twenty six Spirochaetes OTUs, and 16 Synergistetes OTUs were identified (99% identity cut-off). These 'species-level' OTUs were assigned Equine Oral Taxon (EOT) numbers, whose phylogenies and taxonomy were comprehensively investigated, in conjunction with corresponding Synergistetes and Spirochaetes OTUs identified by pyrosequencing. The vast majority of Spirochaetes taxa belonged to the genus Treponema, which corresponded to 7 of the 10 human oral treponeme phylogroups. Other Spirochaetes taxa belonging to the Leptospiraceae family were observed; but many treponemes commonly implicated in animal hoof/foot and non-oral soft tissue infections; e.g. Treponema phagedenis, Treponema pedis, Treponema refringens, Treponema calligyrum; were not identified here. Diverse Synergistetes taxa corresponding to oral clusters A and B were identified, which included Fretibacterium fastidiosum and Pyramidobacter piscolens. Taken together, our data reveals that equine subgingival plaque microbiota shares many similarities with the human, canine and feline oral microbiomes. PMID- 26550764 TI - Moonlight-like proteins of the cell wall protect sessile cells of Candida from oxidative stress. AB - Biofilms of Candida species are associated with high morbidity and hospital mortality. Candida forms biofilms by adhering to human host epithelium through cell wall proteins (CWP) and simultaneously neutralizing the reactive oxygen species (ROS) produced during the respiratory burst by phagocytic cells. The purpose of this paper is to identify the CWP of Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis expressed after exposure to different concentrations of H2O2 using a proteomic approach. CWP obtained from sessile cells, both treated and untreated with the oxidizing agent, were resolved by one and two-dimensional (2D-PAGE) gels and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Some of these proteins were identified and found to correspond to moonlighting CWP such as: (i) glycolytic enzymes, (ii) heat shock, (iii) OSR proteins, (iv) general metabolic enzymes and (v) highly conserved proteins, which are up- or down-regulated in the presence or absence of ROS. We also found that the expression of these CWP is different for each Candida species. Moreover, RT-PCR assays allowed us to demonstrate that transcription of the gene coding for Eno1, one of the moonlight-like CWP identified in response to the oxidant agent, is differentially regulated. To our knowledge this is the first demonstration that, in response to oxidative stress, each species of Candida, differentially regulates the expression of moonlighting CWP, which may protect the organism from the ROS generated during phagocytosis. Presumptively, these proteins allow the pathogen to adhere and form a biofilm, and eventually cause invasive candidiasis in the human host. We propose that, in addition to the antioxidant mechanisms present in Candida, the moonlighting CWP also confer protection to these pathogens from oxidative stress. PMID- 26550765 TI - Reversible Local and Global Switching in Multicomponent Supramolecular Networks: Controlled Guest Release and Capture at the Solution/Solid Interface. AB - Dynamically switchable supramolecular systems offer exciting possibilities in building smart surfaces, the structure and thus the function of which can be controlled by using external stimuli. Here we demonstrate an elegant approach where the guest binding ability of a supramolecular surface can be controlled by inducing structural transitions in it. A physisorbed self-assembled network of a simple hydrogen bonding building block is used as a switching platform. We illustrate that the reversible transition between porous and nonporous networks can be accomplished using an electric field or applying a thermal stimulus. These transitions are used to achieve controlled guest release or capture at the solution-solid interface. The electric field and the temperature-mediated methods of guest release are operative at different length scales. While the former triggers the transition and thus guest release at the nanometer scale, the latter is effective over a much larger scale. The flexibility associated with physisorbed self-assembled networks renders this approach an attractive alternative to conventional switchable systems. PMID- 26550766 TI - Toward a Research Agenda on Pediatric Trauma and Critical Illness. PMID- 26550767 TI - Protective Factors for Adults From Low-Childhood Socioeconomic Circumstances: The Benefits of Shift-and-Persist for Allostatic Load: Erratum. PMID- 26550768 TI - Long-term employment outcomes following traumatic brain injury and orthopaedic trauma: A ten-year prospective study. AB - OBJECTIVE: To investigate the trajectory and predictors of employment over a period of 10 years following traumatic brain injury and traumatic orthopaedic injury. DESIGN: Prospective follow-up at 1, 2, 5 and 10 years post-injury. PARTICIPANTS: Seventy-nine individuals with traumatic brain injury and 79 with traumatic orthopaedic injury recruited from Epworth HealthCare in Melbourne, Australia during inpatient rehabilitation. METHODS: Information was obtained from medical files and self-report questionnaires. RESULTS: Individuals with traumatic brain injury were less likely to be competitively employed during the period up to 10 years post-injury compared with individuals with traumatic orthopaedic injury, although there was evidence of increasing employment participation during that time. More severe traumatic brain injury, older age, pre-injury psychological treatment, and studying or having a blue-collar occupation at time of injury were associated with poorer employment outcomes. Individuals with traumatic brain injury had spent less time with their current employer and were less likely to have increased responsibility since the injury than those with traumatic orthopaedic injury. At least half of each group reported difficulty at work due to fatigue. CONCLUSION: Given the potential for gains in employment participation over an extended time-frame, there may be benefit in ongoing access to individualized vocational rehabilitation. Particular areas of focus would include managing fatigue and psychiatric disorders, and exploring supported occupational activity for all levels of injury severity. PMID- 26550769 TI - Change: The law of life. PMID- 26550770 TI - Determining octanol-water partition coefficients for extremely hydrophobic chemicals by combining "slow stirring" and solid-phase microextraction. AB - Octanol-water partition coefficients (KOW ) are widely used in fate and effects modeling of chemicals. Still, high-quality experimental KOW data are scarce, in particular for very hydrophobic chemicals. This hampers reliable assessments of several fate and effect parameters and the development and validation of new models. One reason for the limited availability of experimental values may relate to the challenging nature of KOW measurements. In the present study, KOW values for 13 polycyclic aromatic hydrocarbons were determined with the gold standard "slow-stirring" method (log KOW 4.6-7.2). These values were then used as reference data for the development of an alternative method for measuring KOW . This approach combined slow stirring and equilibrium sampling of the extremely low aqueous concentrations with polydimethylsiloxane-coated solid-phase microextraction fibers, applying experimentally determined fiber-water partition coefficients. It resulted in KOW values matching the slow-stirring data very well. Therefore, the method was subsequently applied to a series of 17 moderately to extremely hydrophobic petrochemical compounds. The obtained KOW values spanned almost 6 orders of magnitude, with the highest value measuring 10(10.6) . The present study demonstrates that the hydrophobicity domain within which experimental KOW measurements are possible can be extended with the help of solid phase microextraction and that experimentally determined KOW values can exceed the proposed upper limit of 10(9) . Environ Toxicol Chem 2016;35:1371-1377. (c) 2015 SETAC. PMID- 26550771 TI - Bioinspired Nanosucker Array for Enhancing Bioelectricity Generation in Microbial Fuel Cells. AB - A bioinspired active anode with a suction effect is demonstrated for microbial fuel cells by constructing polypyrrole (PPy) nanotubular arrays on carbon textiles. The oxygen in the inner space of the nanosucker can be depleted by micro-organisms with the capability of facul-tative respiration, forming a vacuum, which then activates the electrode to draw the microorganism by suction and thus improve the bioelectricity generation. PMID- 26550772 TI - Efficient genotype compression and analysis of large genetic-variation data sets. AB - Genotype Query Tools (GQT) is an indexing strategy that expedites analyses of genome-variation data sets in Variant Call Format based on sample genotypes, phenotypes and relationships. GQT's compressed genotype index minimizes decompression for analysis, and its performance relative to that of existing methods improves with cohort size. We show substantial (up to 443-fold) gains in performance over existing methods and demonstrate GQT's utility for exploring massive data sets involving thousands to millions of genomes. GQT can be accessed at https://github.com/ryanlayer/gqt. PMID- 26550773 TI - MSPLIT-DIA: sensitive peptide identification for data-independent acquisition. PMID- 26550774 TI - Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe. AB - Photoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ~ 100-MUm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ~ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales. PMID- 26550775 TI - Yield and Textural Characteristics of Panela Cheeses Produced with Dairy Vegetable Protein (Soybean or Peanut) Blends Supplemented with Transglutaminase. AB - The study evaluated panela cheeses made from dairy-plant protein blends, using soybean or peanut protein isolates, supplemented with transglutaminase (TG). Plant proteins were isolated using an alkaline extraction method followed by acid precipitation, and added to the dairy system in order to increase 50% or 100% the protein concentration. The total protein extraction for peanut and soybean isolates was 30.3% and 54.6%, respectively (based on initial protein content of sources), and no impairment of their essential amino acid profile was detected. Cheeses supplemented with TG and soybean showed the highest moisture and crude yield (>67.8% and 20.7%, respectively), whereas protein content was higher in the peanut isolate--added samples without TG (>67.4%). Cheese solids yield (ratio between final and initial solids) was higher for treatments with TG and 100% of plant protein addition (>50.7%). Regarding texture, 4 parameters were measured: hardness, cohesiveness, chewiness, and springiness. All cheeses containing soybean isolates and TG presented the highest chewiness and cohesiveness values, similar to those of the control treatment. Springiness was similar for all treatments, but hardness was higher in cheeses prepared with the peanut protein isolate added with TG. From these results it can be concluded that panela cheeses can be elaborated following a traditional procedure, but with the addition of soybean or peanut protein to the dairy ingredients. Cheeses containing these protein isolates showed higher protein than the milk control cheese and similar textural characteristics. PMID- 26550776 TI - Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. AB - BACKGROUND: Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes. PURPOSE: To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide). DATA SOURCES: MEDLINE, EMBASE, and Ovid Healthstar (inception through 30 June 2015), and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the first quarter of 2015). STUDY SELECTION: 4 researchers double-screened articles for longitudinal studies that compared women with and without breast implants and reported long-term health outcomes of interest. DATA EXTRACTION: 4 researchers extracted data on participant and implant characteristics, analytic methods, and results. DATA SYNTHESIS: 32 studies (in 58 publications) met eligibility criteria. Random effects model meta-analyses of effect sizes were conducted when feasible. For most outcomes, there was at most only a single adequately adjusted study, which usually found no significant associations. There were possible associations with decreased risk for primary breast and endometrial cancers and increased risks for lung cancer, rheumatoid arthritis, Sjogren syndrome, and Raynaud syndrome. Evidence on breast implants and other outcomes either was limited or did not exist. LIMITATION: The evidence was most frequently not specific to silicone gel implants, and studies were rarely adequately adjusted for potential confounders. CONCLUSION: The evidence remains inconclusive about any association between silicone gel implants and long-term health outcomes. Better evidence is needed from existing large studies, which can be reanalyzed to clarify the strength of associations between silicone gel implants and health outcomes. PRIMARY FUNDING SOURCE: The Plastic Surgery Foundation. PMID- 26550777 TI - Characterization of Human CD8(+)TCR(-) Facilitating Cells In Vitro and In Vivo in a NOD/SCID/IL2rgamma(null) Mouse Model. AB - CD8(+)/TCR(-) facilitating cells (FCs) in mouse bone marrow (BM) significantly enhance engraftment of hematopoietic stem/progenitor cells (HSPCs). Human FC phenotype and mechanism of action remain to be defined. We report, for the first time, the phenotypic characterization of human FCs and correlation of phenotype with function. Approximately half of human FCs are CD8(+)/TCR(-)/CD56 negative (CD56(neg)); the remainder are CD8(+)/TCR(-)/CD56 bright (CD56(bright)). The CD56(neg) FC subpopulation significantly promotes homing of HSPCs to BM in nonobese diabetic/severe combined immunodeficiency/IL-2 receptor gamma-chain knockout mouse recipients and enhances hematopoietic colony formation in vitro. The CD56(neg) FC subpopulation promotes rapid reconstitution of donor HSPCs without graft-versus-host disease (GVHD); recipients of CD56(bright) FCs plus HSPCs exhibit low donor chimerism early after transplantation, but the level of chimerism significantly increases with time. Recipients of HSPCs plus CD56(neg) or CD56(bright) FCs showed durable donor chimerism at significantly higher levels in BM. The majority of both FC subpopulations express CXCR4. Coculture of CD56(bright) FCs with HSPCs upregulates cathelicidin and beta-defensin 2, factors that prime responsiveness of HSPCs to stromal cell-derived factor 1. Both FC subpopulations significantly upregulated mRNA expression of the HSPC growth factors and Flt3 ligand. These results indicate that human FCs exert a direct effect on HSPCs to enhance engraftment. Human FCs offer a potential regulatory cell-based therapy for enhancement of engraftment and prevention of GVHD. PMID- 26550778 TI - Host cell protein impurities in chromatographic polishing steps for monoclonal antibody purification. AB - Downstream purification of monoclonal antibodies (mAbs) is normally performed using a platform process that is empirically tuned to optimize impurity removal for each new product. A more fundamental understanding of impurities and the product itself would provide insights into the rational design of efficient downstream processes. This work examines the chromatographic properties of Chinese hamster ovary host cell protein (HCP) impurities in non-affinity chromatographic resins commonly used in polishing steps for monoclonal antibody purification: ion-exchange, hydrophobic interaction, and multimodal. Using proteomic analysis, the specific HCP impurities that elute close to mAb products are identified for these resins at typical downstream processing conditions. Additionally, the interactions of HCP impurities with mAb products are profiled to determine the total extent of product association and the specific HCP species that form associative complexes under conditions encountered in polishing columns. Product association and co-elution were both identified as viable mechanisms of HCP retention for the non-affinity resins tested here. A relatively large sub-population of HCP impurities was found to co-elute or associate with mAbs in each polishing column, but only a small population of HCPs-including lipoprotein lipase, chrondroitin sulfate proteoglycan 4, nidogen-1, and SPARC were identified as difficult to remove across an entire downstream mAb process. Biotechnol. Bioeng. 2016;113: 1260-1272. (c) 2015 Wiley Periodicals, Inc. PMID- 26550779 TI - Moving to a Highly Walkable Neighborhood and Incidence of Hypertension: A Propensity-Score Matched Cohort Study. AB - BACKGROUND: The impact of moving to a neighborhood more conducive to utilitarian walking on the risk of incident hypertension is uncertain. OBJECTIVE: Our study aimed to examine the effect of moving to a highly walkable neighborhood on the risk of incident hypertension. METHODS: A population-based propensity-score matched cohort study design was used based on the Ontario population from the Canadian Community Health Survey (2001-2010). Participants were adults >= 20 years of age who moved from a low-walkability neighborhood (defined as any neighborhood with a Walk Score < 90) to either a high- (Walk Score >= 90) or another low-walkability neighborhood. The incidence of hypertension was assessed by linking the cohort to administrative health databases using a validated algorithm. Propensity-score matched Cox proportional hazard models were used. Annual health examination was used as a control event. RESULTS: Among the 1,057 propensity-score matched pairs there was a significantly lower risk of incident hypertension in the low to high vs. the low to low-walkability groups [hazard ratio = 0.46; 95% CI, 0.26, 0.81, p < 0.01]. The crude hypertension incidence rates were 18.0 per 1,000 person-years (95% CI: 11.6, 24.8) among the low- to low walkability movers compared with 8.6 per 1,000 person-years (95% CI: 5.3, 12.7) among the low- to high-walkability movers (p < 0.001). There were no significant differences in the hazard of annual health examination between the two mover groups. CONCLUSIONS: Moving to a highly walkable neighborhood was associated with a significantly lower risk of incident hypertension. Future research should assess whether specific attributes of walkable neighborhoods (e.g., amenities, density, land-use mix) may be driving this relationship. CITATION: Chiu M, Rezai MR, Maclagan LC, Austin PC, Shah BR, Redelmeier DA, Tu JV. 2016. Moving to a highly walkable neighborhood and incidence of hypertension: a propensity-score matched cohort study. Environ Health Perspect 124:754-760; http://dx.doi.org/10.1289/ehp.1510425. PMID- 26550781 TI - Catalyst performance and mechanism of catalytic combustion of dichloromethane (CH2Cl2) over Ce doped TiO2. AB - TiO2 and Ce/TiO2 were synthesized and subsequently used for the catalytic combustion of DCM. TiO2 had abundant Lewis acid sites and was responsible for the adsorption and the rupture of C-Cl bonds. However, TiO2 tended to be inactivated because of chloride poisoning due to the adsorption and accumulation of Cl species over the surface. While, Ce/TiO2 obtained total oxidation of CH2Cl2 at 335 degrees C and exhibited stable DCM removal activity on 100h long-time stability tests at 330 degrees C without any catalyst deactivation. The doped cerium generated Ce(3+) chemical states and surface active oxygen, and therefore played important roles from two aspects as follows. First of all, the poisoning of Cl for Ce/TiO2 was inhibited to some extent by CeO2 due to the rapid removal of Cl on the surface of CeO2, which has been verified by NH3-IR characterization. In the other hand, CeO2 enhanced the further deep oxidation of C-H from byproducts and retained the certain oxidation of CO to CO2. Based on the DRIFT characterization and the catalysts activity tests, a two-step reaction pathway for the catalytic combustion of DCM on Ce/TiO2 catalyst was proposed. PMID- 26550780 TI - High conversion of HAuCl4 into gold nanorods: A re-seeding approach. AB - Gold nanorods with varying aspect ratios have been utilized in recent years for a wide range of applications including vaccines, surface enhanced Raman spectroscopy (SERS) substrates, and as medicinal therapeutic agents. The surfactant-directed seed mediated approach is an aqueous based protocol that produces monodisperse nanorods with controlled aspect ratios. However, an inherent problem with this approach is poor efficiency of gold conversion from HAuCl4 into nanorods. In fact only ~15% of gold is converted, motivating the need for alternate synthetic protocols in order to make the process more scalable and efficient as gold nanorods progress toward commercial applications. In the current study, we have significantly improved this conversion by growing rods in several iterations of supernatant solutions that were previously discarded as waste. Inductively coupled plasma mass spectrometry (ICP-MS) data indicates ~14% gold conversion per nanorod solution with a total recovery of ~75%. Gold nanorods prepared in consecutive supernatant solutions generally have slightly increased aspect ratios and maintain stability and monodispersity as measured by UV-vis and TEM. The increased nanorod yield minimizes gold waste and results in a greener synthetic approach. PMID- 26550782 TI - Kinetic modeling and design of colloidal lock and key assembly. AB - We investigate the kinetics of colloidal lock and key particle assembly by modeling transitions between free, non-specifically and specifically (dumbbells) bound pairs to enable the rapid formation of specific pairs. We expand on a model introduced in a previous publication (Colon-Melendez et al., 2015) to account for the shape complementarity between the lock and the key particle. Specifically we develop a theory to predict free energy differences between specific and non specific states based on the interaction potential between arbitrary surfaces and apply this to the interaction of a spherical key particle with the concave dimple surface. Our results show that a lock particle dimple slightly wider than the key particle radius results in optimal binding, but also show escape rates much smaller than those observed in experimental measurements described in the paper cited above. We assess the possible sources of error in experiments and in analysis, including spatial and temporal resolution of the confocal microscopy method used to measure kinetic coefficients, the polydispersity of the lock dimple size, and the sedimentation of the particles in a quasi-two-dimensional layer. We find that the largest sources of variation are in the limited temporal resolution of the experiments, which we account for in our theory, and in the quasi-two-dimensional nature of the experiment that leads to misidentification of non-specific pairs as specific ones. Accounting for these sources of variation results in very good quantitative agreement with experimental data. PMID- 26550783 TI - Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery. AB - Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (~180nm) and surface charge ( 30mV). Nanostructured lipid carriers showed a higher cellular uptake and permeability across the barrier, but solid lipid nanoparticles could enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles were able to cross the intestinal barrier by a preferential transcellular route. This work contributed to a better knowledge of the developed nanosystems for the oral delivery of a wide spectrum of drugs. PMID- 26550784 TI - Bio-inspired durable, superhydrophobic magnetic particles for oil/water separation. AB - In the present study, superhydrophobic and superoleophilic microparticles with magnetic property were fabricated by combining the oxidation and self polymerization of dopamine and formation of Fe3O4 nanoparticles on the surface of the polydopamine (PDA) particles, followed by modification with low surface energy material. The modified PDA/Fe3O4 particles showed high water repellency with contact angle (CA) measured at 153.7+/-1.6 degrees and high oil affinity. The superhydrophobic microparticles preserved high water CA after aging test, showing excellent durability. The microparticles were employed to effectively remove oil from water in different routes. Superhydrophobic sponge was prepared by modifying with the achieved microparticles. The sponge exhibited high absorption capability of oil, with weight gains ranging from 1348% to 7268%. The results suggest this work might provide a promising candidate for oily pollutants/water separation and transportation. PMID- 26550785 TI - Static yield stress of a magnetorheological fluid containing Pickering emulsion polymerized Fe2O3/polystyrene composite particles. AB - The flow behaviors of magnetorheological (MR) suspensions containing Pickering emulsion polymerized Fe2O3/polystyrene (PS) composite particles were reanalyzed using the Seo-Seo model. The experimental shear stress data obtained experimentally from the magnetorheological fluid fit well to the Seo-Seo model, indicating that this model can describe the structural reformation process of the aligned fibers at various shear rates. Unlike the dynamic yield stress obtained from the Cho-Choi-Jhon (CCJ) model, the static yield stresses obtained from the Seo-Seo model exhibit the same quadratic dependence on the magnetic field strength for both pure Fe2O3 particle suspension and Fe2O3/PS particle suspensions, which is in agreement with the predictions of the polarization model. The static yield stress plausibly explains the difference in underlying mechanism of MR fluids. PMID- 26550786 TI - Polydopamine-based surface modification of mesoporous silica nanoparticles as pH sensitive drug delivery vehicles for cancer therapy. AB - A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs-DES-PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs-DES-PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs-DES and MSNs-DES-PDA were totally different, and the drug release of MSNs-DES-PDA accelerated with increasing acidity. MSNs-DES-PDA can be internalized into cells. In vitro experiments demonstrated that MSNs-DES-PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy. PMID- 26550787 TI - Evaluation of Efficacy of Bone Scan With SPECT/CT in the Management of Low Back Pain: A Study Supported by Differential Diagnostic Local Anesthetic Blocks. AB - INTRODUCTION: Conventional radiologic modalities provide details only about the anatomic aspect of the various structures of the spine. Frequently the structures that show abnormal morphology may not be the cause of low back pain (LBP). Functional imaging in the form of bone scan along with single photon emission computerized tomography (SPECT/CT) may be helpful in identifying structures causing pain, whether morphologically normal or not. The objective of this study is to evaluate the role of bone scan with SPECT/CT in management of patients with LBP. METHODS: This is randomized double-blinded controlled study performed on 80 patients with LBP aged 20 to 80 years, ASA physical status I to III. Patients were randomized into bone scan and control groups consisting of 40 patients each. On the basis of the clinical features and radiologic findings a clinical diagnosis was made. After making a clinical diagnosis, the patients in bone scan group were subjected to bone scan with SPECT/CT. On the basis of the finding of the bone scan and SPECT/CT, a new working diagnosis was made and intervention was performed according to the new working diagnosis. Diagnostic blocks in the control group were given based on clinical diagnosis. Controlled comparative diagnostic blocks were performed with local anesthetic. The pain score just after the diagnostic block and at the time of discharge (approximately 4 h later) was recorded; the pain relief was recorded in percentage. RESULTS: In both the groups, sacroilitis was the most common diagnosis followed by facet joint arthropathy. The number of patients obtaining pain relief of >50% was significantly higher in the bone scan-positive group as compared with the control group. Three new clinical conditions were identified in the bone scan group. These conditions were multiple myeloma, avascular necrosis of the femoral head, and ankylosing spondylitis. CONCLUSIONS: Bone scan with SPECT/CT was found to complement the clinical workup of patients with LBP. Inclusion of bone scan with SPECT/CT in LBP management protocol can help in making a correct diagnosis. At times it might bring out some new information that may be vital for further management of the patients with LBP. PMID- 26550788 TI - Clinical use of plasma chitotriosidase in severe sepsis. AB - Plasma chitotriosidase activity (ChT) was previously proposed to quantify severity of sepsis. In a complex surgical case, with prolonged sepsis and consistently high ChT, we found that the least increased values occurred in stages of extreme illness, with profound hypocholesterolemia. ChT needs better characterization before becoming a reliable biomarker of septic evolution. PMID- 26550789 TI - Metabolite Profiling and Comparison of Bioactivity in Antrodia cinnamomea and Antrodia salmonea Fruiting Bodies. AB - Antrodia cinnamomea is a precious edible mushroom endemic to Taiwan that has been claimed to have significant health promotion activities. Antrodia salmonea is a new species of the genus Antrodia. In this study, we compared the metabolites and bioactivity of A. cinnamomea and A. salmonea fruiting bodies. The volatiles of A. cinnamomea and A. salmonea were characterized and 3,4,5-trimethoxybenzaldehyde was found to be the most abundant compound in A. cinnamomea; the other abundant compounds were delta-guaiene, isolongifolene, 1-octen-3-ol, 4-terpinenol, alpha guaiene, and p-cymene. In A. salmonea, the main volatiles were alpha-cedrene, 1 octen-3-ol, D-limonene, cadinadiene, germacrene D, isolongifolene, and alpha muurolene. Furthermore, five ergostane-type triterpenoids and two lanostane-type triterpenoids were selected as index compounds characterizing A. cinnamomea and A. salmonea extracts. The content of each compound varied between the two species. (R,S)-antcin B was the most abundant compound in A. cinnamomea fruiting bodies (75.18 +/- 0.11 ug/mg). However, (R,S)-antcin C (184.85 +/- 0.96 ug/mg) was the major triterpenoid in the A. salmonea fruiting body. Furthermore, two compounds, antcin M and methyl antcinate K, were only present in the A. salmonea fingerprint; therefore, antcin M and methyl antcinate K may be important for distinguishing between A. cinnamomea and A. salmonea fruiting bodies. Finally, examination of anti-inflammation activity and cytotoxicity showed that A. salmonea had more anti-inflammatory activity than A. cinnamomea; however, A. salmonea was more cytotoxic than A. cinnamomea. In conclusion, the composition and bioactivity of the fruiting bodies of A. cinnamomea and A. salmonea varies. Therefore, it is recommended that further toxicological evaluation and investigation of the biological activity of A. salmonea is carried out to ensure its safe and efficacious use as an alternative to A. cinnamomea. PMID- 26550790 TI - Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion. AB - Acute kidney injury is a common and severe complication of acute myocardial infarction and cardiac surgery. It results in increased mortality, morbidity, and duration of hospitalization. Baicalein is a component of the root of Scutellaria baicalensis, which has traditionally been used to treat cardiovascular and liver diseases in Asia. In this study, we investigated whether baicalein can attenuate kidney injury induced by myocardial ischemia and reperfusion in rats. Myocardial ischemia and reperfusion, induced by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery, significantly increased blood urea nitrogen and creatinine levels in addition to causing histological changes in the kidneys. Kidney apoptosis was also significantly increased. Furthermore, myocardial ischemia and reperfusion significantly increased the serum levels of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 as well as the tumor necrosis factor-alpha levels in the kidneys. Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion. In addition, the increases in the serum levels of tumor necrosis factor-alpha, interleukin-1, and interleukin-6, and of tumor necrosis factor alpha in the kidneys were significantly reduced. Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys. The phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was also significantly increased. In conclusion, baicalein significantly attenuates kidney injury induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to the inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-alpha production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2. PMID- 26550791 TI - The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition. AB - Glycation, the non-enzymatic binding of glucose to free amino groups of an amino acid, yields irreversible heterogeneous compounds known as advanced glycation end products. Those products play a significant role in diabetic complications. In the present article we briefly discuss the contribution of advanced glycation end products to the pathogenesis of diabetic complications, such as atherosclerosis, diabetic retinopathy, nephropathy, neuropathy, and wound healing. Then we mention the various mechanisms by which polyphenols inhibit the formation of advanced glycation end products. Finally, recent supporting documents are presented to clarify the inhibitory effects of polyphenols on the formation of advanced glycation end products. Phytochemicals apply several antiglycation mechanisms, including glucose metabolism, amelioration of oxidative stress, scavenging of dicarbonyl species, and up/down-regulation of gene expression. To utilize polyphenols in order to remedy diabetic complications, we must explore, examine and clarify the action mechanisms of the components of polyphenols. PMID- 26550793 TI - Improving the Health of Persons With Serious Mental Illness. PMID- 26550792 TI - Case-specific performance of MM-PBSA, MM-GBSA, and SIE in virtual screening. AB - In drug discovery the reliable prediction of binding free energies is of crucial importance. Methods that combine molecular mechanics force fields with continuum solvent models have become popular because of their high accuracy and relatively good computational efficiency. In this research we studied the performance of molecular mechanics generalized Born surface area (MM-GBSA), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and solvated interaction energy (SIE) both in their virtual screening efficiency and their ability to predict experimentally determined binding affinities for five different protein targets. The protein-ligand complexes were derived with two different approaches important in virtual screening: molecular docking and ligand-based similarity search methods. The results show significant differences between the different binding energy calculation methods. However, the length of the molecular dynamics simulation was not of crucial importance for accuracy of results. PMID- 26550794 TI - THE WEBER THESIS OF CALVINISM AND CAPITALISM--ITS VARIOUS VERSIONS AND THEIR "FATE" IN SOCIAL SCIENCE. AB - The paper identifies and examines various multiple renditions of the so-called Weber Thesis of an historical association and convergence between ascetic Protestantism, above all Calvinism, and the emergence and development of modern capitalism as an economic spirit and system. Specifically, it detects at least four different versions and formulations or interpretations, thus casting doubt in the common view of the Weber Thesis as a single and monolithic theory or hypothesis. The paper also considers the status of the multiple versions of the Weber Thesis in post-Weberian and contemporary sociology and related disciplines like economics and history. It concludes that the weaker, relaxed renditions of the Weber Thesis have attained a greater success and more endured in contemporary social science than have its stronger, stricter versions. PMID- 26550796 TI - Furosemide Pharmacokinetics in Adult Rats become Abnormal with an Adverse Intrauterine Environment and Modulated by a Post-Weaning High-Fat Diet. AB - Adult individuals born with intrauterine growth restriction (IUGR) have physiological maladaptations that significantly increase risk of chronic disease. We suggested that such abnormalities in organ function would alter pharmacokinetics throughout life, exacerbated by environmental mismatch. Pregnant and lactating rats were fed either a purified control diet (18% protein) or low protein diet (9% protein) to produce IUGR offspring. Offspring were weaned onto either laboratory chow (11% fat) or high-fat diet (45% fat). Adult offspring (5 months old) were dosed with furosemide (10 mg/kg i.p.) and serum and urine collected. The overall exposure profile in IUGR males was significantly reduced due to a ~35% increase in both clearance and volume of distribution. Females appeared resistant to the IUGR phenotype. The effects of the high-fat diet trended in the opposite direction to that of IUGR, with increased drug exposure due to decreases in both clearance (31% males, 46% females) and volume of distribution (24% males, 44% females), with a 10% longer half-life in both genders. The alterations in furosemide pharmacokinetics and pharmacodynamics were explained by changes in the expression of renal organic anion transporters 1 and 3, and sodium-potassium-chloride cotransporter-2. In summary, this study suggests that IUGR and diet interact to produce subpopulations with similar body-weights but dissimilar pharmacokinetic profiles; this underlines the limitation of one size-fits-all dosing which does not account for physiological differences in body composition resulting from IUGR and diet. PMID- 26550797 TI - Real-time high-frequency colour Doppler ultrasound detection of cutaneous Dermatobia hominis myiasis. PMID- 26550798 TI - In air a spin crossover active iron(II) complex of amine/NCBH3(-) ligands is converted to a low spin complex of imine/CN(-) ligands. AB - Two new mononuclear Fe(II) complexes, [FeL1(NCBH3)2] (1) and [FeL2(CN)2].3H2O (2) (L1 = N,N'-bis(2-pyridylmethyl)-1,2-ethanediamine, L2 = N-(2-pyridylmethyl)-N'-(2 pyridylmethylene)-1,2-ethanediamine) were synthesized from the same starting solution under different atmospheric conditions. Complex 1 was isolated under an N2 atmosphere with an expected molecular structure, namely a tetradentate L1 ligand and two NCBH3(-) co-ligands wrapping an iron(ii) ion. It exhibits a gradual spin crossover centered around 355 K, as confirmed by X-ray crystallography, magnetic, DSC and Mossbauer studies. Complex 2 was isolated in the presence of air. One of the secondary amine groups in L1 undergoes an in situ oxidative dehydrogenation, forming a new monoimine asymmetric ligand L2. Besides, a CN(-) co-ligand is also in situ generated from NCBH3(-) during the reaction. The strong ligand field strength imposed by CN(-) and L2 stabilizes 2 in the LS state. Solvent water molecules in complex 2 are hydrogen bonded into a well defined 1D water chain. 2 shows a proton conductivity of 8.9 * 10(-5) S cm(-1) at 55 degrees C and 95% relative humidity. PMID- 26550800 TI - 'Am I moving?' An illusion of agency and ownership in mirror-touch synaesthesia. AB - Mirror-touch synaesthesia (MTS) is a condition that leads people to experience tactile sensations on their own body when watching at someone else being touched. Recent accounts postulate that MTS is linked with atypical self-other representations. It has been suggested that this may be associated with disturbances in two main components of self-awareness: sense of agency and sense of ownership. This study investigates changes in sense of agency and sense of ownership in MTS. Using a paradigm that deliberately blurs the boundaries between the self and the other, we not only found that MTS affects sense of agency and sense of ownership, but that these aspects of self-awareness are affected differently. We suggest that alterations in sense of agency can be linked to more profound disturbances in sense of ownership in MTS, and that MTS may be characterised by underlying difficulties in self-other processing. PMID- 26550801 TI - Believe it or not: Moving non-biological stimuli believed to have human origin can be represented as human movement. AB - Does our brain treat non-biological movements (e.g. moving abstract shapes or robots) in the same way as human movements? The current work tested whether the movement of a non-biological rectangular object, believed to be based on a human action is represented within the observer's motor system. A novel visuomotor priming task was designed to pit true imitative compatibility, due to human action representation against more general stimulus response compatibility that has confounded previous belief experiments. Stimulus response compatibility effects were found for the object. However, imitative compatibility was found when participants repeated the object task with the belief that the object was based on a human finger movement, and when they performed the task viewing a real human hand. These results provide the first demonstration that non-biological stimuli can be represented as a human movement if they are believed to have human agency and have implications for interactions with technology and robots. PMID- 26550799 TI - The mouse Foxi3 transcription factor is necessary for the development of posterior placodes. AB - The inner ear develops from the otic placode, one of the cranial placodes that arise from a region of ectoderm adjacent to the anterior neural plate called the pre-placodal domain. We have identified a Forkhead family transcription factor, Foxi3, that is expressed in the pre-placodal domain and down-regulated when the otic placode is induced. We now show that Foxi3 mutant mice do not form otic placodes as evidenced by expression changes in early molecular markers and the lack of thickened placodal ectoderm, an otic cup or otocyst. Some preplacodal genes downstream of Foxi3-Gata3, Six1 and Eya1-are not expressed in the ectoderm of Foxi3 mutant mice, and the ectoderm exhibits signs of increased apoptosis. We also show that Fgf signals from the hindbrain and cranial mesoderm, which are necessary for otic placode induction, are received by pre-placodal ectoderm in Foxi3 mutants, but do not initiate otic induction. Finally, we show that the epibranchial placodes that develop in close proximity to the otic placode and the mandibular division of the trigeminal ganglion are missing in Foxi3 mutants. Our data suggest that Foxi3 is necessary to prime pre-placodal ectoderm for the correct interpretation of inductive signals for the otic and epibranchial placodes. PMID- 26550802 TI - Can I cut the Gordian tnok? The impact of pronounceability, actual solvability, and length on intuitive problem assessments of anagrams. AB - When assessing a problem, many cues can be used to predict solvability and solving effort. Some of these cues, however, can be misleading. The present approach shows that a feature of a problem that is actually related to solving difficulty is used as a cue for solving ease when assessing the problem in the first place. For anagrams, it is an established effect that easy-to-pronounce anagrams (e.g., NOGAL) take more time to being solved than hard-to-pronounce anagrams (e.g., HNWEI). However, when assessing an anagram in the first place, individuals use the feature of pronounceability to predict solving ease, because pronounceability is an instantiation of the general mechanism of processing fluency. Participants (total N=536) received short and long anagrams and nonanagrams and judged solvability and solving ease intuitively without actually solving the items. Easy-to-pronounce letter strings were more frequently judged as being solvable than hard-to-pronounce letters strings (Experiment 1), and were estimated to require less effort (Experiments 2, 4-7) and time to be solved (Experiment 3). This effect was robust for short and long items, anagrams and nonanagrams, and presentation timings from 4 down to 0.5s, and affected novices and experts alike. Spontaneous solutions did not mediate this effect. Participants were sensitive to actual solvability even for long anagrams (6-11 letters long) presented only for 500 ms. PMID- 26550804 TI - Reducing genomic instability in iPSCs. PMID- 26550803 TI - Adults with poor reading skills: How lexical knowledge interacts with scores on standardized reading comprehension tests. AB - Millions of adults in the United States lack the necessary literacy skills for most living wage jobs. For students from adult learning classes, we used a lexical decision task to measure their knowledge of words and we used a decision making model (Ratcliff's, 1978, diffusion model) to abstract the mechanisms underlying their performance from their RTs and accuracy. We also collected scores for each participant on standardized IQ tests and standardized reading tests used commonly in the education literature. We found significant correlations between the model's estimates of the strengths with which words are represented in memory and scores for some of the standardized tests but not others. The findings point to the feasibility and utility of combining a test of word knowledge, lexical decision, that is well-established in psycholinguistic research, a decision-making model that supplies information about underlying mechanisms, and standardized tests. The goal for future research is to use this combination of approaches to understand better how basic processes relate to standardized tests with the eventual aim of understanding what these tests are measuring and what the specific difficulties are for individual, low-literacy adults. PMID- 26550805 TI - Single-Electron Transmetalation: Synthesis of 1,1-Diaryl-2,2,2-trifluoroethanes by Photoredox/Nickel Dual Catalytic Cross-Coupling. AB - Novel methods for the incorporation of fluorinated subunits into organic frameworks are important in pharmaceutical, agrochemical, and materials science applications. Herein, the first method for the cross-coupling of benzylic alpha trifluoromethylated alkylboron reagents with (hetero)aryl bromides is achieved through application of a photoredox/nickel dual catalytic system. The harsh conditions and high temperatures required by conventional Suzuki-coupling protocols are avoided by exploitation of an odd-electron pathway that permits room temperature transmetalation of these recalcitrant reagents. This method represents the first direct and general route for the synthesis of unsymmetrical 1,1-diaryl-2,2,2-trifluoroethanes, thereby providing efficient access to a previously unexplored chemical space. PMID- 26550806 TI - A survey of lung cancer in rural and remote Aboriginal and Torres Strait Islander communities in Queensland: health views that impact on early diagnosis and treatment. AB - BACKGROUND: Lung cancer incidence, mortality and hospitalisation rates are higher for Indigenous Australians compared with non-Indigenous Australians and increase again when living in more remote areas. If Indigenous Australians are made more aware of lung cancer through better access to health services and programmes, lung cancer outcomes might improve. AIM: We aimed to survey the level of lung cancer awareness in rural and remote Aboriginal and Torres Strait Islander communities and discover perceived barriers to timely diagnosis and treatment of lung cancer. METHODS: Interviews were conducted in three discrete outer regional and remote Aboriginal communities and one urban setting in Queensland. Participants included Aboriginal and Torres Strait Islander peoples from three target population groups: patients referred for medical treatment with symptoms suspicious of lung cancer or confirmed lung cancer; Indigenous health workers; community members aged 18 years and over. Participants gave written, informed consent. RESULTS: Of 51 community members and 14 Indigenous health workers, 32 reflected they knew very little about lung cancer, 60 cited smoking as the cause of lung cancer and 54 recognised warning symptoms as a prompt to seek healthcare. Indigenous health workers were not able to describe a healthcare pathway that would apply to a patient with suspected lung cancer. CONCLUSION: The two main barriers identified as impacting on quality healthcare were communication and follow-up processes. These could be addressed by service improvement activities. PMID- 26550795 TI - Trial of Continuous or Interrupted Chest Compressions during CPR. AB - BACKGROUND: During cardiopulmonary resuscitation (CPR) in patients with out-of hospital cardiac arrest, the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival. We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations. METHODS: This cluster-randomized trial with crossover included 114 emergency medical service (EMS) agencies. Adults with non trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions (intervention group) or interrupted chest compressions (control group). The primary outcome was the rate of survival to hospital discharge. Secondary outcomes included the modified Rankin scale score (on a scale from 0 to 6, with a score of <=3 indicating favorable neurologic function). CPR process was measured to assess compliance. RESULTS: Of 23,711 patients included in the primary analysis, 12,653 were assigned to the intervention group and 11,058 to the control group. A total of 1129 of 12,613 patients with available data (9.0%) in the intervention group and 1072 of 11,035 with available data (9.7%) in the control group survived until discharge (difference, -0.7 percentage points; 95% confidence interval [CI], -1.5 to 0.1; P=0.07); 7.0% of the patients in the intervention group and 7.7% of those in the control group survived with favorable neurologic function at discharge (difference, -0.6 percentage points; 95% CI, -1.4 to 0.1, P=0.09). Hospital-free survival was significantly shorter in the intervention group than in the control group (mean difference, -0.2 days; 95% CI, -0.3 to -0.1; P=0.004). CONCLUSIONS: In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions. (Funded by the National Heart, Lung, and Blood Institute and others; ROC CCC ClinicalTrials.gov number, NCT01372748.). PMID- 26550807 TI - Posterior capsule opacity in Retinitis Pigmentosa according to different biomaterials of intraocular lenses: Our clinical experience. AB - BACKGROUND AND AIM: Complicated Cataract is frequently associated with Retinitis Pigmentosa (RP). This retinopathy is a great cause of visual impairment, and cataract surgery may resolve partially the situation and restore sight. Unfortunately, in this case there is a very high incidence of Posterior Capsule Opacity (PCO) ranging in several studies a percentage of 100% at six months. Our goal was to evaluate whether the high incidence of PCO is associated to specific type of Intraocular Lens (IOL) biomaterials. MATERIALS AND METHODS: This observational retrospective study deals with 75 eyes of 43 patients affected with RP who underwent to cataract surgery with posterior chamber IOL implants (40% ECCE and 60% Phaco). Selected biomaterials were: 30 Poly (methyl methacrylate) (PMMA), 11 silicone, 34 acrylic. Observations were performed with retro illumination camera and when recorded capsular fibrosis a PCO YAG laser capsulotomy was made. The patients were controlled at 3-6-12 months after the initial surgical treatment. RESULTS: At three months of follow up, 80% of patients with PMMA, 81.8% silicone implants underwent to YAG capsulotomy while only 44% of acrylic type. At six months of follow-up 83.3% of patients with PMMA and 81.8% silicone implants underwent to YAG capsulotomy while only 49.88% of acrylic type. At 12 months of follow up 89.9% of patients with PMMA and 90.95 silicone implants underwent to YAG capsulotomy while only 52.82% of acrylic type. CONCLUSIONS: We could not be able to differentiate incidence between different brand type of lens in PMMA. For Acrylic lens instead we noted an incidence of PCO of 41.38% with hydrophobic material and 60.0% of hydrophilic material. In conclusion to avoid massive PCO in RP, our experience is statistically significant, in fact the protective action of smooth material hydrophobic lens avoids the epithelial growth and fibrosis towards the center of visual axis. PMID- 26550808 TI - [Local and late complications in anorectal surgery]. AB - BACKGROUND AND AIMS: Our experience in colon-proctology showed the need to update the post-surgical complications score we published (1), adding others that may have an impact on outcome of treatment. The aim of this study was to assess the efficacy of a score obtained from the analysis of the quality of life and severity of complications after proctologic surgery. MATERIALS AND METHODS: Between January and December 2013, we studied 150 patients undergoing several ano rectal surgeries for the presence of hemorrhoids of grade III and IV (63 patients), anal fissures (42 patients), anal fistulas (19 patients), rectocele (15 patients) and mucosal prolapse of the rectum (11 patients). After surgery, patients were evaluated through outpatient visits at 3, 6 and 12 months, by a questionnaire concerning the surgery complications and quality of life, the latter expressed with a score from 0 (poor) to 10 (excellent). RESULTS: Only 134 patients [mean age: 49 years (range 35-61 years), 62 M] completed the entire follow-up. The score of complications has been gradually decreasing from 11.3 (baseline) to 9.6 to 3 months, 3.6 to 6 months and 2.3 at 12 months, while the score of the quality of life progressively increased from 4.5 to 6, 8 and 8.5 respectively (p<0.05), with a correlation between the two score (r=-0.6, p= 0.03). CONCLUSIONS: The quantification by scores of quality of life and postoperative complications in colon-proctology is an important prognostic predictor. PMID- 26550809 TI - [Genetic test for cancer and intra-family communication: freedom vs. responsibility]. AB - Genetic tests affect not only single patients but also their genetic relatives. In some cases, they in fact allow to acquire information not only about a single patient, but also about those who are genetically linked (genetic relatives). By appealing to the principle of autonomy, the patient can refuse to be informed of the test result, or to inform their relatives on the risk of a pathology. How might the relatives' right to know be reconciled with the will of a patient who refuses to know or to inform? Among the large number of moral dilemmas that this field can raise, the article aims to reply to the above mentioned question and to analyse in depth some aspects of intra-family communication within the field of genetic tests for cancer. PMID- 26550810 TI - [The involvement of pulmonary interstitial tissue in multisystemic lupus erythematosus: interdisciplinarity and role of the pneumologists]. AB - The Author remarks the interstitial lung involvement in systemic lupus erythematosus. This secondary respiratory manifestation is infrequent as well as the consequent pulmonary hypertension making it possible to miss or delay the diagnosis. Therefore the interdisciplinary evaluation of the multisystemic disease lupus erythematosus needs. In this context the role of the pneumologists is relevant for the global treatment of the patients with LES in particular as concerns the early detection of the clinical and functional respiratory symptoms as well as the appropriate treatment plan within their specialistic competence. PMID- 26550811 TI - The underlying mechanism of action for various medicinal properties of Piper betle (betel). AB - Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine. PMID- 26550812 TI - Facial transplants: current situation and ethical issues. AB - The first transplantation of a face from a cadaver was performed in 2005, since when about thirty have been performed globally. The technique is now beginning to appear in Italy. Face transplants are performed exclusively on persons who have suffered devastating lesions to the face. The ethical problems involved are very considerable, particularly where personal identity is concerned. The case records reveal surprisingly positive outcomes regarding both clinical follow-up and functional recovery, as well as psychological aspects and social integration. Thus, while early documents addressing the ethical issues involved in facial transplants were somewhat cautious or even unfavourable on the subject of this technique, a positive approach is now more prevalent. PMID- 26550813 TI - Randomized and controlled prospective trials of Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia. AB - OBJECTIVE: To evaluate the efficacy of ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia. MATERIALS AND METHODS: 128 cases of lower back or anterior abdominal wall acute post-herpetic neuralgia patients were selected. They were randomly divided into two groups. Group A: oral treatment only with gabapentin + celecoxib + amitriptyline. Group B: while taking these drugs, patients were treated with radiofrequency (RF) pulses using a portable ultrasound device using the paravertebral puncture technique. In both groups, sudden outbreaks of pain were treated with immediate release 10mg morphine tablets. Visual analogue scale (VAS) was used for pain score, Pittsburgh Sleep Quality Index scale (PSQI) was used to evaluate sleep quality and morphine consumption were recorded at different time points, before and after treatment. Treatment efficiency was calculated while the occurrence of complications was documented. RESULTS: At each time point after treatment, VAS scores were lower, but scores in the RF group was significantly lower than those of the oral-only group. In terms of sleep quality scores and morphine consumption between the two groups, the RF group was significantly lower than the oral-only group. During the procedure no error occurred with needle penetrating the abdominal cavity, chest, offal or blood vessels. CONCLUSIONS: Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment of lower back or anterior abdominal wall post-herpetic neuralgia proved effective by reducing morphine use in patients and led to fewer adverse reactions. PMID- 26550814 TI - [Effectiveness of a protocol treatment for overweight/obese patients (SIAN - ASL RMA)]. AB - OBJECTIVES: To evaluate the efficacy of treatment protocols in patients overweight/obese, pertaining to outpatient of dietary preventive of SIAN (in English: Service of Food Hygiene and Nutrition) RMA. MATERIALS AND METHODS: We extracted data from the medical records of patients with BMI>=25 (2009-2012). It was conducted a descriptive analysis, univariate analysis (chi-square test; p<=0.05) and multivariate logistic regression analysis considering as "weight loss" the outcome measure. RESULTS: There were 762 records (76.2% female; mean age 52 years). BMI average of beginning treatment: 30.26; BMI of the end of treatment: 28.37; minimum maximum range of variation of weight after treatment: 28.9 Kg and +6.5 Kg. The 55.2% of the sample has lost up to 4.9 kg, 32.4% from 5.0 to 9.9 kg, 8.1% from 10.0 to 19.9 Kg, 0.9% from 20 to 28.9 Kg. The higher initial BMI and the longer treatment, have a lower likelihood of weight loss (B= 1.267, p<0.001; B =-0.408, p<0.001); females and those who have an older age are more likely to lose weight (B=0.030, p<0.003; B=1.260, p<0.001). CONCLUSIONS: The current study highlight the efficacy of treatment protocols in overweight/obese patients. The population that benefits from the treatment more rigidly set on the estimated caloric needs is the one that starts from lower BMI and who therefore need less time to reach a certain weight loss. Instead, those who started from higher BMI is a population supposedly "binger", more resistant to the single dietary treatment and, as recognized by the scientific community, it requires a multidisciplinary approach. PMID- 26550815 TI - Changes in Transversus Abdominis Muscle Thickness after Lumbo-Pelvic Core Stabilization Training among Chronic Low Back Pain Individuals. AB - OBJECTIVE: Lumbo-pelvic core stabilization training (LPST) is one of the therapeutic exercises common in practice for rehabilitation of patients with chronic low back pain. This study was carried out to examine the therapeutic effects of LPST on the muscle thickness of transversus abdominis (TrA) at rest and during contraction among patients with chronic non-specific low back pain. MATERIALS AND METHODS: A total of 25 participants (7 males and 18 females) with chronic non-specific low back pain participated in a within-subject, repeated measures, double-blinded, placebo-controlled comparisons trial. The participants received three different types of experimental therapeutic training conditions which includes the lumbo-pelvic core stabilization training (LPST), the placebo treatment with passive cycling (PC) and a controlled intervention with rest (CI). The interventions were carried out by randomization with 48 hours between the sessions. The effectiveness of interventions was studied by measuring the changes in muscle thickness of TrA at rest and during contraction using a real time ultrasonography. RESULTS: Repeated measures ANOVA demonstrated that the LPST provided significant therapeutic benefits as measured by an increase in the muscle thickness of the TrA at rest (p<0.05) and during contraction (p<0.01). The percentage change of the muscle thickness observed during LPST was significantly higher (p<0.01) when compared to the other two experimental training conditions. CONCLUSIONS: The findings indicated that the LPST might provide therapeutic benefits by increasing the muscle thickness and function of TrA. Therefore, it is suggested that LPST technique should be considered as part of management program for treatment of low back pain. PMID- 26550816 TI - Prevalence of Diabetes Mellitus (DM) in a population of men affected by Erectile Dysfunction (ED). AB - AIMS: A) to evaluate the prevalence of patients affected by Diabetes Mellitus (DM) in a population of men with Erectile Dysfunction (ED); B) to define the epidemiological, biochemical and therapeutic aspects. MATERIALS AND METHODS: N.934 subjects referred at our Andrology Unit for ED were studied. The diagnosis of ED was evaluated using the IIEF-5 questionnaire (Total score <=21). RESULTS: The prevalence of subjects affected by DM in a population of men with ED was 19.5% (182/934). The age ranges were: >=55 years (108/182; 59.3%); >=40<55 years (70/182; 38.5%); <40 years (4/182; 2.2%). HbA1c mean value was 7.9% +/- 0.8%. No significant differences were found in DM onset timing or in anti-diabetic treatment. In n.125/182 cases (68.7%) the ED onset followed the diagnosis of DM; in n.34/182 cases (18.7%) it appeared at the same time; and in n.23/182 cases (12.6%) appeared before DM diagnosis. ED TREATMENT: in n.18/182 subjects (9.9%) there was a concomitant hypotestosteronemia; these patients were treated only with testosterone replacement; this treatment was efficacious (IIEF-5 total score >=22) in 8/18 subjects (44.4%). In n.146/182 subjects (80.2%) a treatment with PDE5-i was given. Of these 146 subjects, the therapy was given "on demand" to 108 subjects (efficacy in 50.9%; 55/108) and "once a day" to the remaining 38 subjects (efficacy 63.1%, 24/38) (p=0.428, n.s.). N.15/182 subjects (8.2%) were treated with intracavernous injections of Alprostadil (efficacy in 8/15, 53.3%). In n.3/182 subjects (1.6%) a penile prosthesis was implanted. CONCLUSIONS: DM is one of the most frequent organic causes of ED; there were many strategies to treat this symptom without interfering with the antidiabetic treatment. Finally, ED can be predictive of DM. PMID- 26550817 TI - [Evaluation of the combined treatment of oral viscosupplementation with hyaluronic acid intra-articular injection on symptomatic knee osteoarthritis]. AB - OBJECTIVES: Numerous clinical evidences support the treatment of knee OA (KOA) with oral formulations based on hyaluronic acid (HA) and chondroitin sulfate (CS). The formulation aim of the present study (IA) combines a hydrolyzed low molecular weight collagen matrix providing high content of depolymerised HA and CS, with methylsulfonylmethane (MSM), Manganese and a milk glycoprotein. The goal was to evaluate whether combined treatment with intra - articular injection of HA and AI is more effective than treatment with HA only for the symptomatic treatment of knee OA. MATERIALS AND METHODS: Randomized, double-blind, placebo controlled clinical trial. Patients (nr = 100), after undergoing an intra articular injection with HA, were randomized to receive IA or placebo for 3 months. The efficacy of the treatment was assessed by measuring at baseline, 1 and 3 months, the values of the VAS pain scale, the Knee injury and Osteoarthritis Outcome Score, the Tegner Lysholm Knee Scoring Scale, Lequesne algofunctional index and the consumption of NSAIDs and analgesics. RESULTS: The treatment group HA + IA showed a positive trend compared to the group treated with HA only for all the efficacy variables observed, in particular regarding the VAS and the analgesic consumption. CONCLUSIONS: The evidences obtained in this study point out that the oral viscosupplementation with the formulation aim of the present study (IA) represents a valuable, manageable, effective and well tolerated aid, useful to maintain and extend the benefits obtained with intra - articular injection of HA, helping to significantly reduce the use of painkillers by patients. PMID- 26550818 TI - Male ductal carcinoma in situ (DCIS): treatment strategies in this rare entity. AB - Ductal carcinoma in situ (DCIS) in females is a recognized premalignant disease. However, its occurrence in males is rare. Articles describing this disease are scarce with documented occurrence is less than 7% worldwide. We report a case of 52 year-old gentleman presented with 6 months history of left breast lump. It was painless with no nipple discharge. Despite an inconclusive biopsy, lumpectomy was performed in view of the suspicion of malignant disease. Histopathology confirms DCIS. He underwent mastectomy and sentinel lymph nodes. Most treatment strategies are based on evidence on female breast malignancy and modifications are needed due to the different pathological pathway in male. PMID- 26550819 TI - Disordered eating behavior and mental health correlates among treatment seeking obese women. AB - BACKGROUND AND OBJECTIVES: Previous research has suggest that obesity is associated with increased risk for psychopathological disorders, however, little is known about which obese patients are most vulnerable to psychopathological disorders. We therefore investigated 126 treatment-seeking obese women to describe eating disorder pathology and mental health correlates, and to identify disordered eating behaviors that may place obese at increased risk for psychopathological disorders. MATERIALS AND METHODS: The Structured Clinical Interview for DSM-IV (SCID) was used to identify Eating Disorders (ED). A battery of psychological tests, including the Anxiety Scale Questionnaire (ASQ,) Clinical Depression Questionnaire (CDQ), Eating Disorder Inventory-2 (EDI-2) Eating Attitudes Test-26 (EAT-26) scales and structured clinical interview were administered to all the patients. We analyzed the link between psychopathological disorders and eating attitudes by using both multiple regression analysis and non parametric correlation. RESULTS: Disordered eating behaviors and emotional behavioral aspects related to Anorexia Nervosa, such as ineffectiveness, are strongly linked to the depression and anxiety in obese subjects. No correlation was found between psychopathological disorders and age or anthropometric measurements. CONCLUSIONS: Findings corroborate earlier work indicating that psychological distress is elevated in obese treatment seeking, bolstering the need for mental health assessment of such individuals. The feeling of ineffectiveness constitutes the major predictor of psychopathological aspects. This is an important result which may inform the development of effective interventions for obese patients and prevention of psychopathological disorders. PMID- 26550820 TI - [A couple in the sect: between freedom of membership and risks of abuse]. AB - Psychological cults are of particular interest to criminologists due to their complex and multi-faceted structures. They may come in the form of organizations, movements, and training centers that make promises to their victims of developing or strengthening their psycho-relational capacities, thus resulting in improvements in their social, professional, and personal lives. Starting from the complex and delicate story of a professional couple who join a cult, the authors describe one case of a organization that are referred to as "psycho-sects", and with a significant number of followers. These cases came to our attention through judicial authorities, and they offer us an opportunity to look at two aspects associated with psycho-sects: The need of individuals to belong to such groups; and the risk of abuse and violence that they face. PMID- 26550821 TI - Prevention and treatment of nephrolithiasis: a review on the role of spa therapy. AB - The prevalence and incidence of nephrolithiasis is reported to be increasing across the world. It is a disease of increased urinary concentration of stone forming salts. The physicochemical mechanism of stone formation includes precipitation, homogenous/heterogeneous nucleation, growth, aggregation and concretion of various modulators in urine. Necessary condition to develop stones is urinary supersaturation, due to reduced urinary volume or to an excesses solutes. Fluid intake is the main determinant of urine volume. Urine dilution can significantly decrease both the crystallization rate of the urinary salts and the aggregation of the crystals. A correct fluid intake can act on different effects: urinary tract washing, urinary volume increasing and dilution of solutes. In addition mineral waters have other particular features: greater diuretic effect, more important urinary dilution with solutes and microbial concentration reduction, urinary pH changes, superior washout effect due to mechanical effects and ureteral contractions. Adequate water intake is the most important conservative strategy in urolithiasis prevention; particularly hydropinotherapy with oligomineral water should be considered as an important instrument to prevent stones in subjects predisposed to the disease (family members of people suffering from kidney stones), to reduce relapses, and can help to eliminate residual fragments also after extracorporeal shock wave lithotripsy. It is recommended a management with increased mineral water intake to promote urine volume of at least 2.5L each day to prevent stone formation. Obviously water intake shall be varied in relation to the presence of contraindications or any diseases. PMID- 26550822 TI - [Head trauma with clinical and medical legal interest]. AB - In clinical and legal cases some injuries found in living patient or dead body can give rise to difficulties of interpretation regarding the nature of the legally relevant formation mechanism. A field of study that offers often this issue is the brain hemorrhage that it could be traumatic or no traumatic. The authors propose a narrative review of the literature that enables us to recognize in the analysis of the kind of bleeding or type of associated lesions, useful and updated support tools for settlement of the case in question. PMID- 26550823 TI - DNA-dependent formation of transcription factor pairs alters their binding specificity. AB - Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs. However, interactions between DNA-bound TFs have not been systematically characterized. To identify TF pairs that bind cooperatively to DNA, and to characterize their spacing and orientation preferences, we have performed consecutive affinity purification systematic evolution of ligands by exponential enrichment (CAP SELEX) analysis of 9,400 TF-TF-DNA interactions. This analysis revealed 315 TF-TF interactions recognizing 618 heterodimeric motifs, most of which have not been previously described. The observed cooperativity occurred promiscuously between TFs from diverse structural families. Structural analysis of the TF pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their identified recognition site, revealed that the interactions between the TFs were predominantly mediated by DNA. Most TF pair sites identified involved a large overlap between individual TF recognition motifs, and resulted in recognition of composite sites that were markedly different from the individual TF's motifs. Together, our results indicate that the DNA molecule commonly plays an active role in cooperative interactions that define the gene regulatory lexicon. PMID- 26550824 TI - Decapentaplegic and growth control in the developing Drosophila wing. AB - As a central model for morphogen action during animal development, the bone morphogenetic protein 2/4 (BMP2/4)-like ligand Decapentaplegic (Dpp) is proposed to form a long-range signalling gradient that directs both growth and pattern formation during Drosophila wing disc development. While the patterning role of Dpp secreted from a stripe of cells along the anterior-posterior compartmental boundary is well established, the mechanism by which a Dpp gradient directs uniform cell proliferation remains controversial and poorly understood. Here, to determine the precise spatiotemporal requirements for Dpp during wing disc development, we use CRISPR-Cas9-mediated genome editing to generate a flippase recognition target (FRT)-dependent conditional null allele. By genetically removing Dpp from its endogenous stripe domain, we confirm the requirement of Dpp for the activation of a downstream phospho-Mothers against dpp (p-Mad) gradient and the regulation of the patterning targets spalt (sal), optomotor blind (omb; also known as bifid) and brinker (brk). Surprisingly, however, third-instar wing blade primordia devoid of compartmental dpp expression maintain relatively normal rates of cell proliferation and exhibit only mild defects in growth. These results indicate that during the latter half of larval development, the Dpp morphogen gradient emanating from the anterior-posterior compartment boundary is not directly required for wing disc growth. PMID- 26550825 TI - Extra adsorption and adsorbate superlattice formation in metal-organic frameworks. AB - Metal-organic frameworks (MOFs) have a high internal surface area and widely tunable composition, which make them useful for applications involving adsorption, such as hydrogen, methane or carbon dioxide storage. The selectivity and uptake capacity of the adsorption process are determined by interactions involving the adsorbates and their porous host materials. But, although the interactions of adsorbate molecules with the internal MOF surface and also amongst themselves within individual pores have been extensively studied, adsorbate-adsorbate interactions across pore walls have not been explored. Here we show that local strain in the MOF, induced by pore filling, can give rise to collective and long-range adsorbate-adsorbate interactions and the formation of adsorbate superlattices that extend beyond an original MOF unit cell. Specifically, we use in situ small-angle X-ray scattering to track and map the distribution and ordering of adsorbate molecules in five members of the mesoporous MOF-74 series along entire adsorption-desorption isotherms. We find in all cases that the capillary condensation that fills the pores gives rise to the formation of 'extra adsorption domains'-that is, domains spanning several neighbouring pores, which have a higher adsorbate density than non-domain pores. In the case of one MOF, IRMOF-74-V-hex, these domains form a superlattice structure that is difficult to reconcile with the prevailing view of pore-filling as a stochastic process. The visualization of the adsorption process provided by our data, with clear evidence for initial adsorbate aggregation in distinct domains and ordering before an even distribution is finally reached, should help to improve our understanding of this process and may thereby improve our ability to exploit it practically. PMID- 26550826 TI - Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. AB - At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID- 26550829 TI - Molecular Pathology of Adult T-Cell Leukemia/Lymphoma. AB - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm of highly pleomorphic lymphoid cells. ATLL is usually widely disseminated, and it is caused by human T-cell leukemia virus type 1 (HTLV-1). It is a disease with a long latency, and affected individuals are usually exposed to the virus very early in life. The cumulative incidence of ATLL is estimated to be 2.5% among HTLV-1 carriers. ATLL cells express CD2, CD3, CD5, CD4, and CD25, as well as CCR4 and FoxP3 of the regulatory T-cell marker. HTLV-1 is causally linked to ATLL, but infection alone is not sufficient to result in neoplastic transformation. A significant finding in this connection is that the Tax viral protein leads to transcriptional activation of many genes, while the HTLV-1 basic leucine zipper factor is thought to be important for T-cell proliferation and oncogenesis. Half of ATLL cases retain the ability to express HTLV-1 Tax, which is a target of HTLV 1-specific cytotoxic T lymphocytes (CTL). An increase in HTLV-1-specific CTL responses is observed in some asymptomatic HTLV-1 carriers. Although HTLV-1 specific CTL are also present in the peripheral blood of ATLL patients, they do not expand sufficiently. We investigated the clinicopathological features and analyzed the staining of Tax-specific CTL and FoxP3. Tax-specific CTL correlated inversely with FoxP3, an increase in the ratio of CD163+ tumor-associated macrophages was associated with worse clinical prognosis, and ATLL cell lines proliferated significantly following direct co-culture with M2 macrophages. Several clinical variants of ATLL have been identified: acute, lymphomatous, chronic, and smoldering. Oligo-array comparative genomic hybridization revealed that genomic loss of 9p21.3 was a significant characteristic of acute-type, but not of chronic-type ATLL. Furthermore, we found that genomic alteration of CD58, which is implicated in immune escape, is more frequently observed in acute than in chronic ATLL. Interestingly, the chronic cases with cell cycle deregulation and disruption of immunosurveillance mechanism were associated with faster progression to acute ATLL. Immune evasion, microenvironment, and genetic alteration are therefore important in the multi-step progression of ATLL lymphomagenesis. PMID- 26550828 TI - Transcriptional regulators form diverse groups with context-dependent regulatory functions. AB - One of the most important questions in biology is how transcription factors (TFs) and cofactors control enhancer function and thus gene expression. Enhancer activation usually requires combinations of several TFs, indicating that TFs function synergistically and combinatorially. However, while TF binding has been extensively studied, little is known about how combinations of TFs and cofactors control enhancer function once they are bound. It is typically unclear which TFs participate in combinatorial enhancer activation, whether different TFs form functionally distinct groups, or if certain TFs might substitute for each other in defined enhancer contexts. Here we assess the potential regulatory contributions of TFs and cofactors to combinatorial enhancer control with enhancer complementation assays. We recruited GAL4-DNA-binding-domain fusions of 812 Drosophila TFs and cofactors to 24 enhancer contexts and measured enhancer activities by 82,752 luciferase assays in S2 cells. Most factors were functional in at least one context, yet their contributions differed between contexts and varied from repression to activation (up to 289-fold) for individual factors. Based on functional similarities across contexts, we define 15 groups of TFs that differ in developmental functions and protein sequence features. Similar TFs can substitute for each other, enabling enhancer re-engineering by exchanging TF motifs, and TF-cofactor pairs cooperate during enhancer control and interact physically. Overall, we show that activators and repressors can have diverse regulatory functions that typically depend on the enhancer context. The systematic functional characterization of TFs and cofactors should further our understanding of combinatorial enhancer control and gene regulation. PMID- 26550827 TI - Dpp spreading is required for medial but not for lateral wing disc growth. AB - Drosophila Decapentaplegic (Dpp) has served as a paradigm to study morphogen dependent growth control. However, the role of a Dpp gradient in tissue growth remains highly controversial. Two fundamentally different models have been proposed: the 'temporal rule' model suggests that all cells of the wing imaginal disc divide upon a 50% increase in Dpp signalling, whereas the 'growth equalization model' suggests that Dpp is only essential for proliferation control of the central cells. Here, to discriminate between these two models, we generated and used morphotrap, a membrane-tethered anti-green fluorescent protein (GFP) nanobody, which enables immobilization of enhanced (e)GFP::Dpp on the cell surface, thereby abolishing Dpp gradient formation. We find that in the absence of Dpp spreading, wing disc patterning is lost; however, lateral cells still divide at normal rates. These data are consistent with the growth equalization model, but do not fit a global temporal rule model in the wing imaginal disc. PMID- 26550830 TI - Genetic Disorders with Tau Pathology: A Review of the Literature and Report of Two Patients with Tauopathy and Positive Family Histories. AB - BACKGROUND: Tauopathies are a group of neurodegenerative disorders characterized by the pathological accumulation of hyperphosphorylated and insoluble tau protein within neurons and glia. Although most cases are sporadic, hereditary tauopathies have also been reported. SUMMARY: In this article, we review genetic disorders in which tau pathology has been reported and present two novel families with primary tauopathies. Mutations in the microtubule-associated protein tau gene (MAPT) cause a small subset of primary tauopathies. Mutations in 21 other genes and an 18q deletion syndrome have also been reported to be associated with tau pathology reminiscent of Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease or Pick's disease. In 8 of the 21 genes, tau pathology was only seen in cases with some 'specific' mutations. In the remaining genes, tau pathology, often in the form of Alzheimer-type neurofibrillary lesions, was a common finding but was 'not mutation specific'. The probands of the two families were diagnosed with progressive supranuclear palsy based on clinicopathological evaluation. Their family histories were relevant for parkinsonism in 3 siblings of family 1 and 1 brother and the father from family 2, but these were not autopsy-confirmed. DNA from the brains of the probands from these families was screened for MAPT and leucine-rich repeat kinase 2 gene mutations, but no mutations were identified. KEY MESSAGES: MAPT mutations are a cause of familial tauopathies, but other genes have also been associated with tau pathology. Novel genes still await discovery. PMID- 26550831 TI - Anaphylaxis to Intravenous Tramadol in a Child. AB - Hypersensitivity reactions to tramadol are rare and the drug is commonly considered safe. Here, we report the first case of anaphylaxis to tramadol in a child. We point out the difficulty in reaching a confident diagnosis when testing opioid alkaloid drugs with histamine-releasing properties. Additionally, we showed the importance of a well-performed allergy work-up, especially when testing drugs with low experience and when standardized concentrations have not been tested. Moreover, this case provides insight into the possibility of severe reactions, and even anaphylaxis, to tramadol. PMID- 26550832 TI - The Protective Effect of INH2BP, a Novel PARP Inhibitor 5-Iodo-6-Amino-1,2 Benzopyrone, Against Hydrogen Peroxide-Induced Apoptosis Through ERK and p38 MAPK in H9c2 Cells. AB - INH2BP (5-iodo-6-amino-1,2-benzopyrone), a poly-ADP ribose polymerase inhibitor, has been shown to possess anti-cancer, anti-viral, and anti-inflammation properties. The aim of this study was to investigate the protective effect of INH2BP against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells. While the treatment of H9c2 cardiomyoblasts cells with hydrogen peroxide (H2O2) caused a loss of cell viability and an increase in the number of apoptotic cells, INH2BP significantly protected the cells against H2O2-induced cell death without any cytotoxicity. Our data also shows that INH2BP significantly scavenged intracellular reactive oxygen species (ROS), and markedly enhanced the expression of antioxidant enzymes such as Mn-SOD (superoxide) and Cu/Zn-SOD, and heme oxygenase-1, which was accompanied by the concomitant activation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in H9c2 cells. The effects of INH2BP on ERK1/2 and p38 MAPK phosphorylation were abrogated by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. In addition, inhibition of ERK1/2 and p38 MAPK by these inhibitors significantly attenuated INH2BP-mediated H9c2 viability as well as cleaved caspases-3, Bax, and Bcl-2 activation. Taken together, these results demonstrate that INH2BP prevents H2O2-induced apoptosis in H9c2 cells by reducing the production of intracellular ROS, regulating apoptotic-related proteins, and the activation of the ERK1/2 and p38 MAPK. PMID- 26550834 TI - Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience. AB - BACKGROUND: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. METHODS: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. RESULTS: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. CONCLUSION: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life. PMID- 26550833 TI - No Evidence that Infection Alters Global Recombination Rate in House Mice. AB - Recombination rate is a complex trait, with genetic and environmental factors shaping observed patterns of variation. Although recent studies have begun to unravel the genetic basis of recombination rate differences between organisms, less attention has focused on the environmental determinants of crossover rates. Here, we test the effect of one ubiquitous environmental pressure-bacterial infection-on global recombination frequency in mammals. We applied MLH1 mapping to assay global crossover rates in male mice infected with the pathogenic bacterium Borrelia burgdorferi, the causative agent of Lyme Disease, and uninfected control animals. Despite ample statistical power to identify biologically relevant differences between infected and uninfected animals, we find no evidence for a global recombination rate response to bacterial infection. Moreover, broad-scale patterns of crossover distribution, including the number of achiasmate bivalents, are not affected by infection status. Although pathogen exposure can plastically increase recombination in some species, our findings suggest that recombination rates in house mice may be resilient to at least some forms of infection stress. This negative result motivates future experiments with alternative house mouse pathogens to evaluate the generality of this conclusion. PMID- 26550835 TI - Algorithmic Optimisation Method for Improving Use Case Points Estimation. AB - This paper presents a new size estimation method that can be used to estimate size level for software engineering projects. The Algorithmic Optimisation Method is based on Use Case Points and on Multiple Least Square Regression. The method is derived into three phases. The first phase deals with calculation Use Case Points and correction coefficients values. Correction coefficients are obtained by using Multiple Least Square Regression. New project is estimated in the second and third phase. In the second phase Use Case Points parameters for new estimation are set up and in the third phase project estimation is performed. Final estimation is obtained by using newly developed estimation equation, which used two correction coefficients. The Algorithmic Optimisation Method performs approximately 43% better than the Use Case Points method, based on their magnitude of relative error score. All results were evaluated by standard approach: visual inspection, goodness of fit measure and statistical significance. PMID- 26550836 TI - Amenorrhea after Endoscopic Third Ventriculostomy for a Failed Shunt in Spina Bifida: Case Report and Review of the Literature. AB - BACKGROUND: Secondary endoscopic third ventriculostomy (ETV) for the management of shunt failure may be efficacious, though it may be followed by more frequent complications (including endocrinological impairment, e.g., amenorrhea) compared to primary ETV. These complications are usually underreported in the literature. AIM: We report a case of secondary amenorrhea after ETV for the management of shunt failure in a young woman with hydrocephalus associated with myelomeningocele. METHODS: A 25-year-old woman affected by hydrocephalus and myelomeningocele was admitted for secondary ETV for the management of shunt failure. The endoscopic procedure was preferred over shunt revision based on good results of secondary ETV, especially in patients with hydrocephalus associated with Chiari II malformation and spina bifida. RESULTS: Despite the surgery being uneventful, the patient had early (postoperative seizure) and late (secondary amenorrhea) complications. In the early postoperative period, she received external ventricular drainage followed by VP shunt reimplantation 2 weeks later. There was no neurological morbidity, but 1 month after the ETV she reported secondary amenorrhea and weight gain. Laboratory investigations ruled out hyperprolactinemia, which had been treated with cabergoline administration with no efficacy since the patient was still without regular periods 1 year later. CONCLUSION: ETV may be followed by endocrinological complications like amenorrhea that are rarely reported. PMID- 26550837 TI - Heat Transfer in MHD Mixed Convection Flow of a Ferrofluid along a Vertical Channel. AB - This study investigated heat transfer in magnetohydrodynamic (MHD) mixed convection flow of ferrofluid along a vertical channel. The channel with non uniform wall temperatures was taken in a vertical direction with transverse magnetic field. Water with nanoparticles of magnetite (Fe3O4) was selected as a conventional base fluid. In addition, non-magnetic (Al2O3) aluminium oxide nanoparticles were also used. Comparison between magnetic and magnetite nanoparticles were also conducted. Fluid motion was originated due to buoyancy force together with applied pressure gradient. The problem was modelled in terms of partial differential equations with physical boundary conditions. Analytical solutions were obtained for velocity and temperature. Graphical results were plotted and discussed. It was found that temperature and velocity of ferrofluids depend strongly on viscosity and thermal conductivity together with magnetic field. The results of the present study when compared concurred with published work. PMID- 26550839 TI - Organocatalytic Asymmetric Michael/Cyclization Cascade Reactions of 3 Hydroxyoxindoles/3-Aminooxindoles with alpha,beta-Unsaturated Acyl Phosphonates for the Construction of Spirocyclic Oxindole-gamma-lactones/lactams. AB - Enantioselective Michael/cyclization cascade reactions of 3-hydroxyoxindoles/3 aminooxindoles with alpha,beta-unsaturated acyl phosphonates by using a cinchonine derived squaramide as the catalyst were developed. A broad range of spirocyclic oxindole-gamma-lactones/lactams could be obtained in moderate to excellent yields (up to 98%) with good to excellent diastereo- and enantioselectivities (up to >99:1 dr and 97% ee) under mild conditions. This work represents the first example about the alpha,beta-unsaturated acyl phosphonates for the asymmetric construction of spirocyclic oxindoles. PMID- 26550838 TI - Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2. AB - CDK5RAP2 is one of the primary microcephaly genes that are associated with reduced brain size and mental retardation. We have previously shown that human CDK5RAP2 exists as a full-length form (hCDK5RAP2) or an alternatively spliced variant form (hCDK5RAP2-V1) that is lacking exon 32. The equivalent of hCDK5RAP2 V1 has been reported in rat and mouse but the presence of full-length equivalent hCDK5RAP2 in rat and mouse has not been examined. Here, we demonstrate that rat expresses both a full length and an alternatively spliced variant form of CDK5RAP2 that are equivalent to our previously reported hCDK5RAP2 and hCDK5RAP2 V1, repectively. However, mouse expresses only one form of CDK5RAP2 that is equivalent to the human and rat alternatively spliced variant forms. Knowledge of this expression of different forms of CDK5RAP2 in human, rat and mouse is essential in selecting the appropriate model for studies of CDK5RAP2 and primary microcephaly but our findings further indicate the evolutionary divergence of mouse from the human and rat species. PMID- 26550840 TI - Three-Dimensional BC/PEDOT Composite Nanofibers with High Performance for Electrode-Cell Interface. AB - There is an increasing need to synthesize biocompatible nanofibers with excellent mechanical and electrical performance for electrochemical and biomedical applications. Here we report a facile approach to prepare electroactive and flexible 3D nanostructured biomaterials with high performance based on bacterial cellulose (BC) nanofibers. Our approach can coat BC nanofibers with poly(3,4 ethylenedioxythiophene) (PEDOT) by in situ interfacial polymerization in a controllable manner. The PEDOT coating thickness is adjustable by the monomer concentration or reaction time during polymerization, producing nanofibers with a total diameter ranging from 30 to 200 nm. This fabrication process also provides a convenient method to tune different parameters such as the average pore size and electrical conductivity on the demands of actual applications. Our experiments have demonstrated that the 3D BC/PEDOT nanofibers exhibit high specific surface area, excellent mechanical properties, electroactive stability, and low cell cytotoxicity. With electrical stimulation, calcium imaging of PC12 neural cells on BC/PEDOT nanofibers has revealed a significant increase in the percentage of cells with higher action potentials, suggesting an enhanced capacitance effect of charge injection. As an attractive solution to the challenge of designing better electrode-cell interfaces, 3D BC/PEDOT nanofibers promise many important applications such as biosensing devices, smart drug delivery systems, and implantable electrodes for tissue engineering. PMID- 26550841 TI - Ab Initio MD Simulations of the Bronsted Acidity of Glutathione in Aqueous Solutions: Predicting pKa Shifts of the Cysteine Residue. AB - The tripeptide glutathione (GSH) is one of the most abundant peptides and the major repository for nonprotein sulfur in both animal and plant cells. It plays a critical role in intracellular oxidative stress management by the reversible formation of glutathione disulfide with the thiol-disulfide pair acting as a redox buffer. The state of charge of the ionizable groups of GSH can influence the redox couple, and hence the pKa value of the cysteine residue of GSH is critical to its functioning. Here we report ab initio Car-Parrinello molecular dynamics simulations of glutathione solvated by 200 water molecules, all of which are considered in the simulation. We show that the free-energy landscape for the protonation-deprotonation reaction of the cysteine residue of GSH computed using metadynamics sampling provides accurate estimates of the pKa and correctly predicts the shift in the dissociation constant values as compared with the isolated cysteine amino acid. PMID- 26550842 TI - Metal-based optical probes for live cell imaging of nitroxyl (HNO). AB - Nitroxyl (HNO) is a biological signaling agent that displays distinctive reactivity compared to nitric oxide (NO). As a consequence, these two reactive nitrogen species trigger different physiological responses. Selective detection of HNO over NO has been a challenge for chemists, and several fluorogenic molecular probes have been recently developed with that goal in mind. Common constructs take advantage of the HNO-induced reduction of Cu(II) to Cu(I). The sensing mechanism of such probes relies on the ability of the unpaired electron in a d orbital of the Cu(II) center to quench the fluorescence of a photoemissive ligand by either an electron or energy transfer mechanism. Experimental and theoretical mechanistic studies suggest that proton-coupled electron transfer mediates this process, and careful tuning of the copper coordination environment has led to sensors with optimized selectivity and kinetics. The current optical probes cover the visible and near-infrared regions of the spectrum. This palette of sensors comprises structurally and functionally diverse fluorophores such as coumarin (blue/green emission), boron dipyrromethane (BODIPY, green emission), benzoresorufin (red emission), and dihydroxanthenes (near-infrared emission). Many of these sensors have been successfully applied to detect HNO production in live cells. For example, copper-based optical probes have been used to detect HNO production in live mammalian cells that have been treated with H2S and various nitrosating agents. These studies have established a link between HSNO, the smallest S-nitrosothiol, and HNO. In addition, a near-infrared HNO sensor has been used to perform multicolor/multianalyte microscopy, revealing that exogenously applied HNO elevates the concentration of intracellular mobile zinc. This mobilization of zinc ions is presumably a consequence of nitrosation of cysteine residues in zinc-chelating proteins such as metallothionein. Future challenges for the optical imaging of HNO include devising probes that can detect HNO reversibly, especially because ratiometric imaging can only report equilibrium concentrations when the sensing event is reversible. Another important aspect that needs to be addressed is the creation of probes that can sense HNO in specific subcellular locations. These tools would be useful to identify the organelles in which HNO is produced in mammalian cells and probe the intracellular signaling networks in which this reactive nitrogen species is involved. In addition, near-infrared emitting probes might be applied to detect HNO in thicker specimens, such as acute tissue slices and even live animals, enabling the investigation of the roles of HNO in physiological or pathological conditions in multicellular systems. PMID- 26550843 TI - Superior Oxygen Stability of N-Heterocyclic Carbene-Coated Au Nanocrystals: Comparison with Dodecanethiol. AB - The stability of Au nanocrystals (NCs) coated with different N-heterocyclic carbenes (NHCs) or dodecanethiol (DDT) to oxygen-based treatments was investigated. A dominant effect of the ligand type was observed with a significantly greater oxygen resistance of NHC-coated Au NCs compared to that of the thiol-based analogues. NHC-coated Au NCs are stable to 10 W oxygen plasma etching for up to 180 s whereas the integrity of DDT-coated Au NCs is strongly affected by the same treatment from 60-80 s. In the latter case, the average size of the NCs (from 2.6 to 6.3 nm) and the method of synthesis have no effect on the stability. NHC-coated Au NCs were found to generate of a smaller quantity of ligand-derived species under molecular oxygen treatment, which could account for the increased stability. PMID- 26550845 TI - Periodicity, Electronic Structures, and Bonding of Gold Tetrahalides [AuX4]- (X = F, Cl, Br, I, At, Uus). AB - Systematic theoretical and experimental investigations have been performed to understand the periodicity, electronic structures, and bonding of gold halides using tetrahalide [AuX4](-) anions (X = F, Cl, Br, I, At, Uus). The [AuX4](-) (X = Cl, Br, I) anions were experimentally produced in the gas phase, and their negative-ion photoelectron spectra were obtained, exhibiting rich and well resolved spectral peaks. As expected, Au-X bonds in such series contain generally increasing covalency when halogen ligands become heavier. We calculated the adiabatic electron detachment energies as well as vertical electron detachment energies using density functional theory methods with scalar relativistic and spin-orbit coupling effects. The computationally simulated photoelectron spectra are in good agreement with the experimental ones. Our results show that the trivalent Au(III) oxidation state becomes progressively less stable while Au(I) tends to be preferred when the halides become heavier along the Periodic Table. This series of molecules provides an example for manipulating the oxidation state of metals in complexes through ligand design. PMID- 26550844 TI - 4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino} 3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel. AB - Recent post hoc analyses of several clinical trials with P2Y12 antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y12 antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model. PMID- 26550846 TI - Variation in Alkaloid Production from Genetically Diverse Lolium Accessions Infected with Epichloe Species. AB - Widespread infection of Epichloe occultans in annual ryegrass in Australia suggests that infection provides its weedy host, Lolium rigidum, some ecological advantage. Initial studies determined the distribution and profiles of known Epichloe alkaloids (epoxy-janthitrems, ergovaline, lolines, lolitrem B, and peramine) in plant extracts using a combination of GC-FID and HPLC techniques utilizing a single accession of Australian L. rigidum. However, the lolines N acetylnorloline (NANL) and N-formylloline (NFL) were the only alkaloids detected and were highly concentrated in the immature inflorescences of mature plants. Additional glasshouse studies subjected a wide range of Australian L. rigidum haplotypes and international annual Lolium accessions to a suite of analyses to determine alkaloid levels and profiles. Again, NFL and NANL were the key lolines produced, with NFL consistently predominating. Considerable variation in alkaloid production was found both within and between biotypes and accessions evaluated under identical conditions, at the same maturation stage and on the same tissue type. The pyrrolopyrazine alkaloid peramine was also present in 8 out of 17 Australian biotypes of L. rigidum and 7 out of 33 international accessions infected with Epichloe spp.; the highest peramine concentrations were observed in seed extracts from L. rigidum collected from Australia. This study represents the first report of alkaloids from a geographically diverse collection of annual ryegrass germplasm infected with Epichloe spp. when grown under identical controlled conditions. PMID- 26550848 TI - E-Selective Semi-Hydrogenation of Alkynes by Heterobimetallic Catalysis. AB - A unique cooperative H2 activation reaction by heterobimetallic (NHC)M'-MCp(CO)2 complexes (NHC = N-heterocyclic carbene, M' = Cu or Ag, M = Fe or Ru) has been leveraged to develop a catalytic alkyne semi-hydrogenation transformation. The optimal Ag-Ru catalyst gives high selectivity for converting alkynes to E alkenes, a rare selectivity mode for reduction reactions with H2. The transformation is tolerant of many reducible functional groups. Computational analysis of H2 activation thermodynamics guided rational catalyst development. Bimetallic alkyne hydrogenation and alkene isomerization mechanisms are proposed. PMID- 26550849 TI - Perylene Bisimide as a Promising Zinc Oxide Surface Modifier: Enhanced Interfacial Combination for Highly Efficient Inverted Polymer Solar Cells. AB - We report the application of a perylene bisimide (PBI-H) as zinc oxide (ZnO) surface modifier to afford an organic-inorganic co-interlayer for highly efficient inverted organic photovoltaics (i-OPV). By thermal annealing, a N-Zn chemical bond formed between PBI-H and ZnO, inducing close organic-inorganic combination. In addition, this co-interlayer shows decreased work function and increased electron transportation and conductivity, which are benefits for the cathode to enhance charge extraction efficiency and decrease recombination losses. As a result a highly efficient i-OPV was achieved with a power conversion efficiency (PCE) of 9.43% based on this co-interlayer with PTB7:PC71BM as the active layer, which shows over 35% enhancement compared to that of the device without the PBI-H layer. Moreover, this co-interlayer was widely applicable for i OPVs based on various material systems, such as P3HT:PC61BM and PTB7-Th:PC71BM, resulting in PCE as high as 4.78% and 10.31%, respectively. PMID- 26550847 TI - p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET. AB - Zirconium-89 has an ideal half-life for use in antibody-based PET imaging; however, when used with the chelator DFO, there is an accumulation of radioactivity in the bone, suggesting that the (89)Zr(4+) cation is being released in vivo. Therefore, a more robust chelator for (89)Zr could reduce the in vivo release and the dose to nontarget tissues. Evaluation of the ligand 3,4,3 (LI-1,2-HOPO) demonstrated efficient binding of (89)Zr(4+) and high stability; therefore, we developed a bifunctional derivative, p-SCN-Bn-HOPO, for conjugation to an antibody. A Zr-HOPO crystal structure was obtained showing that the Zr is fully coordinated by the octadentate HOPO ligand, as expected, forming a stable complex. p-SCN-Bn-HOPO was synthesized through a novel pathway. Both p-SCN-Bn HOPO and p-SCN-Bn-DFO were conjugated to trastuzumab and radiolabeled with (89)Zr. Both complexes labeled efficiently and achieved specific activities of approximately 2 mCi/mg. PET imaging studies in nude mice with BT474 tumors (n = 4) showed good tumor uptake for both compounds, but with a marked decrease in bone uptake for the (89)Zr-HOPO-trastuzumab images. Biodistribution data confirmed the lower bone activity, measuring 17.0%ID/g in the bone at 336 h for (89)Zr-DFO-trastuzumab while (89)Zr-HOPO-trastuzumab only had 2.4%ID/g. We successfully synthesized p-SCN-Bn-HOPO, a bifunctional derivative of 3,4,3-(LI 1,2-HOPO) as a potential chelator for (89)Zr. In vivo studies demonstrate the successful use of (89)Zr-HOPO-trastuzumab to image BT474 breast cancer with low background, good tumor to organ contrast, and, importantly, very low bone uptake. The reduced bone uptake seen with (89)Zr-HOPO-trastuzumab suggests superior stability of the (89)Zr-HOPO complex. PMID- 26550850 TI - Impact of Capacitive Effect and Ion Migration on the Hysteretic Behavior of Perovskite Solar Cells. AB - In the past five years, perovskite solar cells (PSCs) based on organometal halide perovskite have exhibited extraordinary photovoltaic (PV) performance. However, the PV measurements of PSCs have been widely recognized to depend on voltage scanning condition (hysteretic current density-voltage [J-V] behavior), as well as on voltage treatment history. In this study, we find that varied PSC responses are attributable to two causes. First, capacitive effect associated with electrode polarization provides a slow transient non-steady-state photocurrent that modifies the J-V response. Second, modification of interfacial barriers induced by ion migration can modulate charge-collection efficiency so that it causes a pseudo-steady-state photocurrent, which changes according to previous voltage conditioning. Both phenomena are strongly influenced by ions accumulating at outer interfaces, but their electrical and PV effects are different. The time scale for decay of capacitive current is on the order of seconds, whereas the slow redistribution of mobile ions requires several minutes. PMID- 26550851 TI - Preparation of N-Substituted N-Arylsulfonylglycines and Their Use in Peptoid Synthesis. AB - To increase the chemical diversity accessible with peptoids and peptide-peptoid hybrids, N-alkylated arylsulfonamides were used to prepare side chain protected N substituted glycines compatible with solid-phase synthesis. The described procedures give access to peptoid monomers bearing a wide variety of functional groups from commercially available amines in four straightforward steps. The prepared N-substituted N-arylsulfonylglycines were used as monomers in solid phase synthesis to introduce relevant functionalized side chains into peptoid oligomers and peptide-peptoid hybrids. PMID- 26550852 TI - Quasiparticle Properties of a Mobile Impurity in a Bose-Einstein Condensate. AB - We develop a systematic perturbation theory for the quasiparticle properties of a single impurity immersed in a Bose-Einstein condensate. Analytical results are derived for the impurity energy, effective mass, and residue to third order in the impurity-boson scattering length. The energy is shown to depend logarithmically on the scattering length to third order, whereas the residue and the effective mass are given by analytical power series. When the boson-boson scattering length equals the boson-impurity scattering length, the energy has the same structure as that of a weakly interacting Bose gas, including terms of the Lee-Huang-Yang and fourth order logarithmic form. Our results, which cannot be obtained within the canonical Frohlich model of an impurity interacting with phonons, provide valuable benchmarks for many-body theories and for experiments. PMID- 26550853 TI - From Floquet to Dicke: Quantum Spin Hall Insulator Interacting with Quantum Light. AB - Time-periodic perturbations due to classical electromagnetic fields are useful to engineer the topological properties of matter using the Floquet theory. Here we investigate the effect of quantized electromagnetic fields by focusing on the quantized light-matter interaction on the edge state of a quantum spin Hall insulator. A Dicke-type superradiant phase transition occurs at arbitrary weak coupling, the electronic spectrum acquires a finite gap, and the resulting ground state manifold is topological with a Chern number of +/-1. When the total number of excitations is conserved, a photocurrent is generated along the edge, being pseudoquantized as omegaln(1/omega) in the low-frequency limit and decaying as 1/omega for high frequencies with omega the photon frequency. The photon spectral function exhibits a clean Goldstone mode, a Higgs-like collective mode at the optical gap and the polariton continuum. PMID- 26550854 TI - Controlled Rephasing of Single Collective Spin Excitations in a Cold Atomic Quantum Memory. AB - We demonstrate active control of inhomogeneous dephasing and rephasing for single collective atomic spin excitations (spin waves) created by spontaneous Raman scattering in a quantum memory based on cold 87Rb atoms. The control is provided by a reversible external magnetic field gradient inducing an inhomogeneous broadening of the atomic hyperfine levels. We demonstrate experimentally that active rephasing preserves the single photon nature of the retrieved photons. Finally, we show that the control of the inhomogeneous dephasing enables the creation of time-separated spin waves in a single ensemble followed by a selective read-out in time. This is an important step towards the implementation of a functional temporally multiplexed quantum repeater node. PMID- 26550855 TI - Phase-Reference-Free Experiment of Measurement-Device-Independent Quantum Key Distribution. AB - Measurement-device-independent quantum key distribution (MDI QKD) is a substantial step toward practical information-theoretic security for key sharing between remote legitimate users (Alice and Bob). As with other standard device dependent quantum key distribution protocols, such as BB84, MDI QKD assumes that the reference frames have been shared between Alice and Bob. In practice, a nontrivial alignment procedure is often necessary, which requires system resources and may significantly reduce the secure key generation rate. Here, we propose a phase-coding reference-frame-independent MDI QKD scheme that requires no phase alignment between the interferometers of two distant legitimate parties. As a demonstration, a proof-of-principle experiment using Faraday-Michelson interferometers is presented. The experimental system worked at 1 MHz, and an average secure key rate of 8.309 bps was obtained at a fiber length of 20 km between Alice and Bob. The system can maintain a positive key generation rate without phase compensation under normal conditions. The results exhibit the feasibility of our system for use in mature MDI QKD devices and its value for network scenarios. PMID- 26550856 TI - Experimental Generation of Robust Entanglement from Classical Correlations via Local Dissipation. AB - We experimentally show how classical correlations can be turned into quantum entanglement, via the presence of dissipation and the action of a CNOT gate. We first implement a simple two-qubit protocol in which entanglement production is not possible in the absence of such kind of noise, while it arises with its introduction, and is proportional to its amount. We then perform a more elaborate four-qubit experiment, by employing two hyperentangled photons initially carrying only classical correlations. We demonstrate a scheme where the entanglement is generated via local dissipation, with the advantage of being robust against local unitaries performed by an adversary. PMID- 26550857 TI - Proposal for High-Fidelity Quantum Simulation Using a Hybrid Dressed State. AB - A fundamental goal of quantum technologies concerns the exploitation of quantum coherent dynamics for the realization of novel quantum applications such as quantum computing, quantum simulation, and quantum metrology. A key challenge on the way towards these goals remains the protection of quantum coherent dynamics from environmental noise. Here, we propose a concept of a hybrid dressed state from a pair of continuously driven systems. It allows sufficiently strong driving fields to suppress the effect of environmental noise while at the same time being insusceptible to both the amplitude and phase noise in the continuous driving fields. This combination of robust features significantly enhances coherence times under realistic conditions and at the same time provides new flexibility in Hamiltonian engineering that otherwise is not achievable. We demonstrate theoretically applications of our scheme for a noise-resistant analog quantum simulation in the well-studied physical systems of nitrogen-vacancy centers in diamond and of trapped ions. The scheme may also be exploited for quantum computation and quantum metrology. PMID- 26550858 TI - Quantum Hilbert Hotel. AB - In 1924 David Hilbert conceived a paradoxical tale involving a hotel with an infinite number of rooms to illustrate some aspects of the mathematical notion of "infinity." In continuous-variable quantum mechanics we routinely make use of infinite state spaces: here we show that such a theoretical apparatus can accommodate an analog of Hilbert's hotel paradox. We devise a protocol that, mimicking what happens to the guests of the hotel, maps the amplitudes of an infinite eigenbasis to twice their original quantum number in a coherent and deterministic manner, producing infinitely many unoccupied levels in the process. We demonstrate the feasibility of the protocol by experimentally realizing it on the orbital angular momentum of a paraxial field. This new non-Gaussian operation may be exploited, for example, for enhancing the sensitivity of NOON states, for increasing the capacity of a channel, or for multiplexing multiple channels into a single one. PMID- 26550859 TI - Compactness of Neutron Stars. AB - Recent progress in the determination of both masses and radii of neutron stars is starting to place stringent constraints on the dense matter equation of state. In particular, new theoretical developments together with improved statistical tools seem to favor stellar radii that are significantly smaller than those predicted by models using purely nucleonic equations of state. Given that the underlying equation of state must also account for the observation of 2M? neutron stars, theoretical approaches to the study of the dense matter equation of state are facing serious challenges. In response to this challenge, we compute the underlying equation of state associated with an assumed mass-radius template similar to the "common radius" assumption used in recent studies. Once such a mass-radius template is adopted, the equation of state follows directly from the implementation of Lindblom's algorithm; assumptions on the nature or composition of the dense stellar core are not required. By analyzing mass-radius profiles with a maximum mass consistent with observation and common radii in the 8-11 km range, a lower limit on the stellar radius of a 1.4M? neutron star of RNS?10.7 km is required to prevent the equation of state from violating causality. PMID- 26550860 TI - Checking the Dark Matter Origin of a 3.53 keV Line with the Milky Way Center. AB - We detect a line at 3.539+/-0.011 keV in the deep exposure data set of the Galactic center region, observed with the x-ray multi-mirror mission Newton. The dark matter interpretation of the signal observed in the Perseus galaxy cluster, the Andromeda galaxy [A. Boyarsky et al., Phys. Rev. Lett. 113, 251301 (2014)], and in the stacked spectra of galaxy clusters [E. Bulbul et al., Astrophys. J. 789, 13 (2014)], together with nonobservation of the line in blank-sky data, put both lower and upper limits on the possible intensity of the line in the Galactic center data. Our result is consistent with these constraints for a class of Milky Way mass models, presented previously by observers, and would correspond to the radiative decay dark matter lifetime, tauDM~6-8*10(27) sec. Although it is hard to exclude an astrophysical origin of this line based on the Galactic center data alone, this is an important consistency check of the hypothesis that encourages us to check it with more observational data that are expected by the end of 2015. PMID- 26550861 TI - Theoretically Palatable Flavor Combinations of Astrophysical Neutrinos. AB - The flavor composition of high-energy astrophysical neutrinos can reveal the physics governing their production, propagation, and interaction. The IceCube Collaboration has published the first experimental determination of the ratio of the flux in each flavor to the total. We present, as a theoretical counterpart, new results for the allowed ranges of flavor ratios at Earth for arbitrary flavor ratios in the sources. Our results will allow IceCube to more quickly identify when their data imply standard physics, a general class of new physics with arbitrary (incoherent) combinations of mass eigenstates, or new physics that goes beyond that, e.g., with terms that dominate the Hamiltonian at high energy. PMID- 26550862 TI - Effect of New Physics in Astrophysical Neutrino Flavor. AB - Astrophysical neutrinos are powerful tools for investigating the fundamental properties of particle physics through their flavor content. In this Letter, we perform the first general new physics study on ultrahigh energy neutrino flavor content by introducing effective operators. We find that, at the current limits on these operators, new physics terms cause maximal effects on the flavor content; however, the flavor content on the Earth is confined to a region related to the assumed initial flavor content. Furthermore, we conclude that a precise measure of the flavor content on the Earth will provide orders of magnitude improvement on new physics bounds. Finally, we discuss the current best fits of flavor content of the IceCube data and their interplay with new physics scenarios. PMID- 26550863 TI - Exact Path Integral for 3D Quantum Gravity. AB - Three-dimensional Euclidean pure gravity with a negative cosmological constant can be formulated in terms of the Chern-Simons theory, classically. This theory can be written in a supersymmetric way by introducing auxiliary gauginos and scalars. We calculate the exact partition function of this Chern-Simons theory by using the localization technique. Thus, we obtain the quantum gravity partition function, assuming that it can be obtained nonperturbatively by summing over partition functions of the Chern-Simons theory on topologically different manifolds. The resultant partition function is modular invariant, and, in the case in which the central charge is expected to be 24, it is the J function, predicted by Witten. PMID- 26550865 TI - Goldstone Gauginos. AB - Models of supersymmetry with Dirac gauginos provide an attractive scenario for physics beyond the standard model. The "supersoft" radiative corrections and suppressed supersymmetry production at colliders provide for more natural theories and an understanding of why no new states have been seen. Unfortunately, these models are handicapped by a tachyon which is naturally present in existing models of Dirac gauginos. We argue that this tachyon is absent, with the phenomenological successes of the model preserved, if the right-handed gaugino is a (pseudo-)Goldstone field of a spontaneously broken anomalous flavor symmetry. PMID- 26550867 TI - Disentangling Mass and Mixing Hierarchies. AB - We present a fully perturbative mechanism that naturally generates mass hierarchies for the standard model (SM) fermions in a flavor-blind sector. The dynamics generating the mass hierarchies can therefore be independent from the source of flavor violation, and hence this dynamics may operate at a much lower scale. This mechanism works by dynamically enforcing simultaneous diagonalization -alignment--among a set of flavor-breaking spurions, as well as generating highly singular spectra for them. It also has general applications in model building beyond the SM, wherever alignment between exotic and SM sources of flavor violation is desired. PMID- 26550868 TI - Beyond-Standard-Model Tensor Interaction and Hadron Phenomenology. AB - We evaluate the impact of recent developments in hadron phenomenology on extracting possible fundamental tensor interactions beyond the standard model. We show that a novel class of observables, including the chiral-odd generalized parton distributions, and the transversity parton distribution function can contribute to the constraints on this quantity. Experimental extractions of the tensor hadronic matrix elements, if sufficiently precise, will provide a, so far, absent testing ground for lattice QCD calculations. PMID- 26550869 TI - Mass Measurement of 56Sc Reveals a Small A = 56 Odd-Even Mass Staggering, Implying a Cooler Accreted Neutron Star Crust. AB - We present the mass excesses of (52-57)Sc, obtained from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. The masses of 56Sc and 57Sc were determined for the first time with atomic mass excesses of -24.85(59)((-54)(+0)) MeV and -21.0(1.3) MeV, respectively, where the asymmetric uncertainty for 56Sc was included due to possible contamination from a long-lived isomer. The 56Sc mass indicates a small odd-even mass staggering in the A = 56 mass chain towards the neutron drip line, significantly deviating from trends predicted by the global FRDM mass model and favoring trends predicted by the UNEDF0 and UNEDF1 density functional calculations. Together with new shell-model calculations of the electron-capture strength function of 56Sc, our results strongly reduce uncertainties in model calculations of the heating and cooling at the 56Ti electron-capture layer in the outer crust of accreting neutron stars. We find that, in contrast to previous studies, neither strong neutrino cooling nor strong heating occurs in this layer. We conclude that Urca cooling in the outer crusts of accreting neutron stars that exhibit superbursts or high temperature steady-state burning, which are predicted to be rich in A~56 nuclei, is considerably weaker than predicted. Urca cooling must instead be dominated by electron capture on the small amounts of adjacent odd-A nuclei contained in the superburst and high temperature steady-state burning ashes. This may explain the absence of strong crust Urca cooling inferred from the observed cooling light curve of the transiently accreting x-ray source MAXI J0556-332. PMID- 26550871 TI - Sagnac Interferometry with a Single Atomic Clock. AB - The Sagnac effect enables interferometric measurements of rotation with high precision. Using matter waves instead of light promises resolution enhancement by orders of magnitude that scales with particle mass. So far, the paradigm for matter wave Sagnac interferometry relies on de Broglie waves and thus on free propagation of atoms either in free fall or within waveguides. However, the Sagnac effect can be expressed as a proper time difference experienced by two observers moving in opposite directions along closed paths and has indeed been measured with atomic clocks flown around Earth. Inspired by this, we investigate an interferometer comprised of a single atomic clock. The Sagnac effect manifests as a phase shift between trapped atoms in different internal states after transportation along closed paths in opposite directions, without any free propagation. With analytic models, we quantify limitations of the scheme arising from atomic dynamics and finite temperature. Furthermore, we suggest an implementation with previously demonstrated technology. PMID- 26550872 TI - Spin-Mixing Interferometry with Bose-Einstein Condensates. AB - Unstable spinor Bose-Einstein condensates are ideal candidates to create nonlinear three-mode interferometers. Our analysis goes beyond the standard SU(1,1) parametric approach and therefore provides the regime of parameters where sub-shot-noise sensitivities can be reached with respect to the input total average number of particles. Decoherence due to particle losses and finite detection efficiency are also considered. PMID- 26550873 TI - Probe of Rydberg-Atom Transitions via an Amplitude-Modulated Optical Standing Wave with a Ponderomotive Interaction. AB - In ponderomotive spectroscopy an amplitude-modulated optical standing wave is employed to probe Rydberg-atom transitions, utilizing a ponderomotive rather than a dipole-field interaction. Here, we engage nonlinearities in the modulation to drive dipole-forbidden transitions up to the fifth order. We reach transition frequencies approaching the sub-THz regime. We also demonstrate magic-wavelength conditions, which result in symmetric spectral lines with a Fourier-limited peak at the line center. Applicability to precision measurement is discussed. PMID- 26550874 TI - Self-Ordered Limit Cycles, Chaos, and Phase Slippage with a Superfluid inside an Optical Resonator. AB - We study dynamical phases of a driven Bose-Einstein condensate coupled to the light field of a high-Q optical cavity. For high field seeking atoms at red detuning the system is known to show a transition from a spatially homogeneous steady state to a self-ordered regular lattice exhibiting superradiant scattering into the cavity. For blue atom pump detuning the particles are repelled from the maxima of the light-induced optical potential suppressing scattering. We show that this generates a new dynamical instability of the self-ordered phase, leading to the appearance of self-ordered stable limit cycles characterized by large amplitude self-sustained oscillations of both the condensate density and cavity field. The limit cycles evolve into chaotic behavior by period doubling. Large amplitude oscillations of the condensate are accompanied by phase slippage through soliton nucleation at a rate that increases in the chaotic regime. Different from a superfluid in a closed setup, this driven dissipative superfluid is not destroyed by the proliferation of solitons since kinetic energy is removed through cavity losses. PMID- 26550870 TI - Observation of Gravitationally Induced Vertical Striation of Polarized Ultracold Neutrons by Spin-Echo Spectroscopy. AB - We describe a spin-echo method for ultracold neutrons (UCNs) confined in a precession chamber and exposed to a |B0|=1 MUT magnetic field. We have demonstrated that the analysis of UCN spin-echo resonance signals in combination with knowledge of the ambient magnetic field provides an excellent method by which to reconstruct the energy spectrum of a confined ensemble of neutrons. The method takes advantage of the relative dephasing of spins arising from a gravitationally induced striation of stored UCNs of different energies, and also permits an improved determination of the vertical magnetic-field gradient with an exceptional accuracy of 1.1 pT/cm. This novel combination of a well-known nuclear resonance method and gravitationally induced vertical striation is unique in the realm of nuclear and particle physics and should prove to be invaluable for the assessment of systematic effects in precision experiments such as searches for an electric dipole moment of the neutron or the measurement of the neutron lifetime. PMID- 26550875 TI - Above-Threshold Ionization of Quasiperiodic Structures by Low-Frequency Laser Fields. AB - We investigate the theoretical problem of the photoelectron cutoff change in periodical structures induced by an infrared laser field. We use a one dimensional Kronig-Penney potential including a finite number of wells, and the analysis is fulfilled by resolving the time-dependent Schrodinger equation. The electron spectra, calculated for an increasing number of wells, clearly show that a plateau quickly appears as the periodic nature of the potential builds up, even at a moderate intensity (10 TW/cm(2)). Varying the intensity from 10 to 30 TW/cm(2) we observe a net increase of both the yield and accessible energy range of the ionization spectrum. In order to gain insight into the dynamics of the system at these intensities, we use an analytical approach, based on exact solutions of the full Hamiltonian in a periodic potential. We show that the population transfers efficiently from lower to upper bands when the Bloch and laser frequencies become comparable. The model leads to a quantitative prediction of the intensity range where ionization enters the nonperturbative regime. Moreover, it reveals the physics underlying the increase of the photoelectron energy cutoff at moderate intensities, as observed experimentally. PMID- 26550876 TI - Deterministic Generation of Arbitrary Photonic States Assisted by Dissipation. AB - A scheme to utilize atomlike emitters coupled to nanophotonic waveguides is proposed for the generation of many-body entangled states and for the reversible mapping of these states of matter to photonic states of an optical pulse in the waveguide. Our protocol makes use of decoherence-free subspaces (DFSs) for the atomic emitters with coherent evolution within the DFSs enforced by strong dissipative coupling to the waveguide. By switching from subradiant to superradiant states, entangled atomic states are mapped to photonic states with high fidelity. An implementation using ultracold atoms coupled to a photonic crystal waveguide is discussed. PMID- 26550877 TI - Generation of Terahertz Surface Plasmon Polaritons Using Nondiffractive Bessel Beams with Orbital Angular Momentum. AB - Bessel vortex beams with topological charges of l=+/-1 and l=+/-2 were produced in the terahertz spectral range from a free electron laser Gaussian beam (lambda=141 MUm) transformed using silicon binary diffractive optical elements. The spatial characteristics of the beams were obtained using a microbolometer array. A radius to path length ratio of 1:100 was achieved for nondiffractive beams with the average power of 30 W. Surface plasmon polaritons (SPPs) on gold zinc-sulphide-air interfaces were generated due to diffraction of vortex beams on a sample edge. A new effect, a dependence of the efficiency of SPP generation on the direction of the azimuthal component of incident-radiation Poynting vector, was revealed. PMID- 26550878 TI - Synchronization and Phase Noise Reduction in Micromechanical Oscillator Arrays Coupled through Light. AB - Synchronization of many coupled oscillators is widely found in nature and has the potential to revolutionize timing technologies. Here, we demonstrate synchronization in arrays of silicon nitride micromechanical oscillators coupled in an all-to-all configuration purely through an optical radiation field. We show that the phase noise of the synchronized oscillators can be improved by almost 10 dB below the phase noise limit for each individual oscillator. These results open a practical route towards synchronized oscillator networks. PMID- 26550879 TI - Wettability Stabilizes Fluid Invasion into Porous Media via Nonlocal, Cooperative Pore Filling. AB - We study the impact of the wetting properties on the immiscible displacement of a viscous fluid in disordered porous media. We present a novel pore-scale model that captures wettability and dynamic effects, including the spatiotemporal nonlocality associated with interface readjustments. Our simulations show that increasing the wettability of the invading fluid (the contact angle) promotes cooperative pore filling that stabilizes the invasion and that this effect is suppressed as the flow rate increases, due to viscous instabilities. We use scaling analysis to derive two dimensionless numbers that predict the mode of displacement. By elucidating the underlying mechanisms, we explain classical yet intriguing experimental observations. These insights could be used to improve technologies such as hydraulic fracturing, CO2 geosequestration, and microfluidics. PMID- 26550880 TI - Blockage of Water Flow in Carbon Nanotubes by Ions Due to Interactions between Cations and Aromatic Rings. AB - Combining classical molecular dynamics simulations and density functional theory calculations, we find that cations block water flow through narrow (6,6)-type carbon nanotubes (CNTs) because of interactions between cations and aromatic rings in CNTs. In wide CNTs, these interactions trap the cations in the interior of the CNT, inducing unexpected open or closed state switching of ion transfer under a strong electric field, which is consistent with experiments. These findings will help to develop new methods to facilitate water and ion transport across CNTs. PMID- 26550881 TI - Lattice-Assisted Spectroscopy: A Generalized Scanning Tunneling Microscope for Ultracold Atoms. AB - We propose a scheme to measure the frequency-resolved local particle and hole spectra of any optical lattice-confined system of correlated ultracold atoms that offers single-site addressing and imaging, which is now an experimental reality. Combining perturbation theory and time-dependent density matrix renormalization group simulations, we quantitatively test and validate this approach of lattice assisted spectroscopy on several one-dimensional example systems, such as the superfluid and Mott insulator, with and without a parabolic trap, and finally on edge states of the bosonic Su-Schrieffer-Heeger model. We highlight extensions of our basic scheme to obtain an even wider variety of interesting and important frequency resolved spectra. PMID- 26550864 TI - Search for Violation of CPT and Lorentz Invariance in Bs(0) Meson Oscillations. AB - We present the first search for CPT-violating effects in the mixing of Bs(0) mesons using the full Run II data set with an integrated luminosity of 10.4 fb( 1) of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. We measure the CPT-violating asymmetry in the decay Bs(0)->MU(+/-)Ds(+/-) as a function of celestial direction and sidereal phase. We find no evidence for CPT-violating effects and place limits on the direction and magnitude of flavor-dependent CPT- and Lorentz-invariance violating coupling coefficients. We find 95% confidence intervals of Deltaa?<1.2*10(-12) GeV and ( 0.8D(-) charge transition we can increase the tunnel rates to a nearby single electron transistor charge sensor by nearly 2 orders of magnitude, allowing faster qubit read-out (1 ms) with minimum loss in read-out fidelity (98.4%) compared to read out at the D(+)<->D(0) transition (99.6%). Furthermore, we show that read-out via the D(-) charge state can be used to rapidly initialize the electron spin qubit in its ground state with a fidelity of F(I)=99.8%. PMID- 26550897 TI - Emergent SU(3) Symmetry in Random Spin-1 Chains. AB - We show that generic SU(2)-invariant random spin-1 chains have phases with an emergent SU(3) symmetry. We map out the full zero-temperature phase diagram and identify two different phases: (i) a conventional random-singlet phase (RSP) of strongly bound spin pairs [SU(3) "mesons"] and (ii) an unconventional RSP of bound SU(3) "baryons," which are formed, in the great majority, by spin trios located at random positions. The emergent SU(3) symmetry dictates that susceptibilities and correlation functions of both dipolar and quadrupolar spin operators have the same asymptotic behavior. PMID- 26550898 TI - Resonating-Valence-Bond Physics Is Not Always Governed by the Shortest Tunneling Loops. AB - It is well known that the low-energy sector of quantum spin liquids and other magnetically disordered systems is governed by short-ranged resonating-valence bonds. Here we show that the standard minimal truncation to the nearest-neighbor valence-bond basis fails completely even for systems where it should work the most, according to received wisdom. This paradigm shift is demonstrated for the quantum spin-1/2 square kagome, where strong geometric frustration, similar to the kagome, prevents magnetic ordering down to zero temperature. The shortest tunneling events bear the strongest longer-range singlet fluctuations, leading to amplitudes that do not drop exponentially with the length of the loop L, and to an unexpected loop-six valence-bond crystal, which is otherwise very high in energy at the minimal truncation level. The low-energy effective description gives in addition a clear example of correlated loop processes that depend not only on the type of the loop but also on its lattice embedding, a direct manifestation of the long-range nature of the virtual singlets. PMID- 26550899 TI - Rare-Earth Triangular Lattice Spin Liquid: A Single-Crystal Study of YbMgGaO4. AB - YbMgGaO4, a structurally perfect two-dimensional triangular lattice with an odd number of electrons per unit cell and spin-orbit entangled effective spin-1/2 local moments for the Yb(3+) ions, is likely to experimentally realize the quantum spin liquid ground state. We report the first experimental characterization of single-crystal YbMgGaO4 samples. Because of the spin-orbit entanglement, the interaction between the neighboring Yb(3+) moments depends on the bond orientations and is highly anisotropic in the spin space. We carry out thermodynamic and the electron spin resonance measurements to confirm the anisotropic nature of the spin interaction as well as to quantitatively determine the couplings. Our result is a first step towards the theoretical understanding of the possible quantum spin liquid ground state in this system and sheds new light on the search for quantum spin liquids in strong spin-orbit coupled insulators. PMID- 26550900 TI - First-Principles Study of the Magnetic Structure of Na2IrO3. AB - The iridate Na2IrO3 was proposed to be a realization of the Kitaev model with a quantum spin liquid ground state. Experiments have now established that this material hosts a zigzag antiferromagnetic order. However, the previous assignment of the ordered moment direction to the a axis is controversial. We examine the magnetic moment direction of Na2IrO3 using the local spin density approximation plus spin orbit coupling+U calculations. Our calculations reveal that the total energy is minimized when the zigzag-ordered moments are aligned along g~a+c direction. The dependence of the total energy on moment directions can be explained by adding anisotropic interactions to the nearest-neighbor Kitaev Heisenberg model, on which the spin-wave spectrum is also calculated. The revision of ordered moments is very important to understanding and achieving possible exotic electronic phases in this compound. PMID- 26550901 TI - Adjacent Fe-Vacancy Interactions as the Origin of Room Temperature Ferromagnetism in (In(1-x)Fe(x))2O3. AB - Dilute magnetic semiconductors (DMSs) show great promise for applications in spin based electronics, but in most cases continue to elude explanations of their magnetic behavior. Here, we combine quantitative x-ray spectroscopy and Anderson impurity model calculations to study ferromagnetic Fe-substituted In2O3 films, and we identify a subset of Fe atoms adjacent to oxygen vacancies in the crystal lattice which are responsible for the observed room temperature ferromagnetism. Using resonant inelastic x-ray scattering, we map out the near gap electronic structure and provide further support for this conclusion. Serving as a concrete verification of recent theoretical results and indirect experimental evidence, these results solidify the role of impurity-vacancy coupling in oxide-based DMSs. PMID- 26550902 TI - General Differential Contact Identities for Macromolecules. AB - We discuss general Maxwell identities relating a macromolecule's charge, the forces acting at its surface, and the osmotic pressure of the solution in which it sits. The identities are closely related to the contact value relations that hold for certain special geometries, but are more general. In particular, the Maxwell identities can be applied to any macromolecule geometry, and they hold both within and outside of mean-field theory. Examples illustrate that combining the identities with approximate treatments of screening can often return simple, accurate osmotic pressure estimates. PMID- 26550903 TI - Criticality in the Approach to Failure in Amorphous Solids. AB - Failure of amorphous solids is fundamental to various phenomena, including landslides and earthquakes. Recent experiments indicate that highly plastic regions form elongated structures that are especially apparent near the maximal shear stress Sigmamax where failure occurs. This observation suggested that Sigmamax acts as a critical point where the length scale of those structures diverges, possibly causing macroscopic transient shear bands. Here, we argue instead that the entire solid phase (SigmaK(*0)MU(+)MU(-) Decays. AB - A search is presented for hidden-sector bosons, chi, produced in the decay B(0) >K*(892)(0)chi, with K*(892)(0)->K(+)pi(-) and chi->MU(+)MU(-). The search is performed using pp-collision data corresponding to 3.0 fb(-1) collected with the LHCb detector. No significant signal is observed in the accessible mass range 214<=m(chi)<=4350 MeV, and upper limits are placed on the branching fraction product B(B(0)->K*(892)(0)chi)*B(chi->MU(+)MU(-)) as a function of the mass and lifetime of the chi boson. These limits are of the order of 10(-9) for chi lifetimes less than 100 ps over most of the m(chi) range, and place the most stringent constraints to date on many theories that predict the existence of additional low-mass bosons. PMID- 26550904 TI - Propulsion and Instability of a Flexible Helical Rod Rotating in a Viscous Fluid. AB - We combine experiments with simulations to investigate the fluid-structure interaction of a flexible helical rod rotating in a viscous fluid, under low Reynolds number conditions. Our analysis takes into account the coupling between the geometrically nonlinear behavior of the elastic rod with a nonlocal hydrodynamic model for the fluid loading. We quantify the resulting propulsive force, as well as the buckling instability of the originally helical filament that occurs above a critical rotation velocity. A scaling analysis is performed to rationalize the onset of this instability. A universal phase diagram is constructed to map out the region of successful propulsion and the corresponding boundary of stability is established. Comparing our results with data for flagellated bacteria suggests that this instability may be exploited in nature for physiological purposes. PMID- 26550905 TI - Three-Dimensional Conformation of Folded Polymers in Single Crystals. AB - The chain-folding mechanism and structure of semicrystalline polymers have long been controversial. Solid-state NMR was applied to determine the chain trajectory of (13)C CH3-labeled isotactic poly(1-butene) (iPB1) in form III chiral single crystals blended with nonlabeled iPB1 crystallized in dilute solutions under low supercooling. An advanced (13)C-(13)C double-quantum NMR technique probing the spatial proximity pattern of labeled (13)C nuclei revealed that the chains adopt a three-dimensional (3D) conformation in single crystals. The determined results indicate a two-step crystallization process of (i) cluster formation via self folding in the precrystallization stage and (ii) deposition of the nanoclusters as a building block at the growth front in single crystals. PMID- 26550906 TI - Comment on "General Non-Markovian Dynamics of Open Quantum Systems". PMID- 26550907 TI - Zhang et al. Reply. PMID- 26550908 TI - Erratum: New Steady-State Quiescent High-Confinement Plasma in an Experimental Advanced Superconducting Tokamak [Phys. Rev. Lett. 114, 055001 (2015)]. PMID- 26550909 TI - Publisher's Note: Decay and Fission Hindrance of Two- and Four-Quasiparticle K Isomers in (254)Rf [Phys. Rev. Lett. 115, 132502 (2015)]. PMID- 26550910 TI - Photodynamic therapy for basal cell carcinoma. AB - Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma. PMID- 26550911 TI - Characterization of emissions from a desktop 3D printer and indoor air measurements in office settings. AB - Emissions from a desktop 3D printer based on fused deposition modeling (FDM) technology were measured in a test chamber and indoor air was monitored in office settings. Ultrafine aerosol (UFA) emissions were higher while printing a standard object with polylactic acid (PLA) than with acrylonitrile butadiene styrene (ABS) polymer (2.1 * 10(9) vs. 2.4 * 10(8) particles/min). Prolonged use of the printer led to higher emission rates (factor 2 with PLA and 4 with ABS, measured after seven months of occasional use). UFA consisted mainly of volatile droplets, and some small (100-300 nm diameter) iron containing and soot-like particles were found. Emissions of inhalable and respirable dust were below the limit of detection (LOD) when measured gravimetrically, and only slightly higher than background when measured with an aerosol spectrometer. Emissions of volatile organic compounds (VOC) were in the range of 10 ug/min. Styrene accounted for more than 50% of total VOC emitted when printing with ABS; for PLA, methyl methacrylate (MMA, 37% of TVOC) was detected as the predominant compound. Two polycyclic aromatic hydrocarbons (PAH), fluoranthene and pyrene, were observed in very low amounts. All other analyzed PAH, as well as inorganic gases and metal emissions except iron (Fe) and zinc (Zn), were below the LOD or did not differ from background without printing. A single 3D print (165 min) in a large, well ventilated office did not significantly increase the UFA and VOC concentrations, whereas these were readily detectable in a small, unventilated room, with UFA concentrations increasing by 2,000 particles/cm(3) and MMA reaching a peak of 21 ug/m(3) and still being detectable in the room even 20 hr after printing. PMID- 26550912 TI - Altered force perception in stroke survivors with spastic hemiplegia. AB - OBJECTIVE: To investigate the effect of spasticity and involuntary synergistic activation on force perception during voluntary activation of spastic paretic muscles. METHODS: Eleven stroke subjects with spastic hemiparesis performed various isometric elbow-flexion force-matching tasks. Subjects were instructed to generate a target reference force with visual feedback using one arm (impaired or non-impaired) and then to produce a force with the other arm to match the magnitude of the reference force without visual feedback. The reference arm was at rest in unilateral exertion trials and maintained contraction in bilateral exertion trials during the matching force-production period. RESULTS: Both force and effort mismatches occurred in most conditions, and there were asymmetries in force perception. When the non-impaired arm was the matching arm, effort and force overestimation occurred, but effort was matched better than force. When the impaired arm was the matching arm, force underestimation and effort overestimation occurred, but force was matched better than effort. No difference in matching performance was found between unilateral and bilateral exertion matching tasks. CONCLUSION: Overall, both force and effort misperceptions occur in stroke survivors with spasticity. Spasticity and spastic synergistic activation probably contribute to force and effort misperception during voluntary activation in chronic stroke. PMID- 26550913 TI - [Psychological adjustment following lower limb amputation]. AB - Rehabilitation of lower limb amputees and the fitting of their prosthesis depend highly on the psychological adjustment process and motivational state of the patient. The loss of a limb is extremely challenging and can cause various physical and psychological problems. Depression, anxiety, decreased well-being and quality of life, body image dissatisfaction and changes in self-concept and identity are frequent after lower limb amputation. In the interest of adjustment patients have to cope with the emerging changes and difficulties in their lifes as well as the problems in psychological functioning. It is important for them to accept the alterations in their body and identity, and integrate them in a new self-concept in which process motivation is a fundamental issue. The aim of this article is to review the literature on psychological consequences of lower limb amputation, and to propose an integrative way of rehabilitation for lower limb amputees. PMID- 26550914 TI - [New perspectives of mourning]. AB - Grief is a natural part of life and it is always individual. Researchers have tried and still try to develop different theories to interpret, explain, and approach this particular phenomenon. The aim of the authors was to review the theoretical literature of mourning and to present new bereavement theories for domestic professionals. From the first half of the 20th century until presently mourning theories have undergone significant changes. Today the determinant models includes the flexible, coping-oriented dual process model, meaning reconstruction model which focuses on the meaning making, and the model which focuses on the development after the loss. The authors conclude that experts, who work in the clinical area should know the prevailing theories of grief, because they encounter often with loss at work. The presented models may contribute to more efficient work, to better understanding of the mourning process and to a better support of families. PMID- 26550915 TI - [Prognostic factors in light chain amyloidosis]. AB - INTRODUCTION: Light chain amyloidosis is characterized by extracellular deposition of a fibrillar material derived from immunglobulin light chain fragments. AIM: The aim of the authors was to assess survival depending on cardiac involvement, therapy, and presence of myeloma. METHOD: The authors studied a retrospective cohort of 29 patients with light chain amyloidosis (13 kappa, 16 lambda) treated in their institution between 2005 and 2014. RESULTS: Twenty-one patients had primary amyloidosis, while 8 had coexisting multiple myeloma. One, two and three or more organs were involved in 4, 8, and 17 patients, respectively. Cardiac involvement (22 cases) inversely correlated with survival. Fifteen (52%) patients received chemotherapy only, while 14 (48%) underwent autologous stem cell transplantation with a median survival of 87 and 11.4 months, respectively. Two patients had heart transplantation and survived 70 and 30 months. Median overall survival was 75.8 months. CONCLUSIONS: Cardiac transplantation followed by autologous stem cell transplantation is feasible in selected patients with light chain amyloidosis and heart failure. PMID- 26550916 TI - [Minimally invasive surgical treatment of ulcerative colitis--long-term results]. AB - INTRODUCTION: For the surgical treatment of ulcerative colitis, laparoscopy is used more widely, but less data are available on long-term results in Hungary. AIM: The aim of the authors was to compare the mean 47.8-month follow-up results of patients treated with conventional and minimally invasive surgical methods. METHOD: Between January 1, 2005 and December 31, 2014, 56 patients were treated with surgery (20 emergencies, and 36 elective cases). Laparoscopy was used in 33 and conventional method in 23 cases. RESULTS: There was no difference between the two groups in hospital and intensive care unit stay, bowel function recovery, need for transfusion, and complications during the perioperative period. Regarding long-term complications, the occurrence of intestinal obstruction, septic condition and other complications were significantly fewer in the laparoscopy group. The quality of life improved in both groups after the surgery. CONCLUSIONS: Laparoscopy can be used safely; it provides good quality of life and better cosmetic results, and the long-term rate of complications is lower as compared to open surgery. PMID- 26550917 TI - [Stereotactic radiosurgery of abdominal cancer metastases. Report on the first successful extracranial radiosurgical intervention in Hungary]. AB - Due to the development and increasing effectiveness of novel cancer therapies, the role of local treatments in metastatic diseases have been increasing in the last decades. The aim of the authors was to present the first successful extracranial stereotactic radiosurgical intervention in Hungary. A 58-year-old male patient with gastric adenocarcinoma underwent surgery and adjuvant chemotherapy. Later, surgical removal of suprarenal gland metastases and first line chemotherapy were carried out. Four years after the first surgery a follow up computed tomographic scan revealed bifocal peritoneal metastases caudally from the edge of the liver and the left kidney with diameters of 2 cm in size. Definitive stereotactic body radiosurgery of 12 Gy single dose was performed using cone beam computed tomography image guidance and intensity modulated arc therapy with two pairs of arcs. The total duration of the procedure was only 25 min and early or late side effects were not observed. Follow up computed tomography scans performed 3 and 7 months after the intervention showed complete regression of the metastases. The authors conclude that stereotactic body radiosurgery can be a safe and effective alternative of metastasis surgery in case of slow growing oligo-metastases. PMID- 26550918 TI - Analyzing the anti-ischemia-reperfusion injury effects of ginsenoside Rb1 mediated through the inhibition of p38alpha MAPK. AB - Recent studies have demonstrated that ginsenoside Rb1 protects the myocardium from ischemia-reperfusion (I/R) injury. However, the precise mechanisms for this protection have not been determined. This study aimed to determine whether the attenuation of I/R-induced myocardial injury by ginsenoside Rb1 (GS Rb1) is due to inhibition of p38alpha mitogen-activated protein kinase (MAPK). Sprague-Dawley rats were distributed among 6 treatment groups: sham group; I/R group; p38 MAPK inhibitor SB203580 group (SB + I/R); GS Rb1 group (GS + I/R); p38 MAPK agonist anisomycin group (Ani + I/R); and the GS Rb1 + Ani group (GS + Ani + I/R). All of the anaesthetized rats, except those in the sham group, underwent an open-chest procedure that involved 30 min of myocardial ischemia followed by 2 h of reperfusion. Myocardial infarction size (MIS), caspase-3 activity, and levels of the cytokine tumor necrosis factor alpha (TNF-alpha) in the myocardium were monitored. The expressions of p38alpha MAPK, caspase-3, and TNF-alpha in the myocardium were assayed. GS Rb1 reduced MIS and attenuated caspase-3 activity and the levels of TNF-alpha in the myocardium. Protein expression of total p38alpha MAPK was not significantly altered. In the Ani + I/R and I/R groups, the levels of phospho-p38alpha MAPK were significantly increased compared with the sham group, and these increased levels were reduced with GS Rb1. Hemodynamic parameters were not significantly different between the GS + I/R and SB + I/R groups. GS Rb1 exerts an anti-apoptotic effect that protects against I/R injury by inhibiting p38alpha MAPK phosphorylation, suggesting that GS Rb1-mediated protection requires the inhibition of p38alpha MAPK. PMID- 26550919 TI - Are urge incontinence and aging risk factors of erectile dysfunction in patients with male lower urinary tract symptoms? AB - INTRODUCTION: Several studies have indicated that erectile dysfunction (ED) patients also suffer from lower urinary tract symptoms (LUTS). We investigated a group of men with LUTS and assessed their sexual function with the aim of being able to predict ED risk factors and introduce ED treatments earlier for this patient group. METHODS: International Prostate Symptom Score (IPSS), Overactive Bladder Symptoms Score (OABSS) and Sexual Health Inventory for Men (SHIM) score were obtained from 236 men with LUTS at their first out-patients visit. Clinical parameters such as body mass index, prostate volume, residual urine volume and prostate specific antigen were also evaluated. The relationship between the SHIM score and other clinical data was analyzed. RESULTS: According to the SHIM score, ED in men with LUTS was severe 15%, moderate 19%, moderate to mild 28%, mild 17%, normal 7% and data was incomplete in 14%. Based on the results of a multivariate analysis, aging (p < 0.001) and OAB severity (p = 0.024) were significantly correlated to severe and moderate ED. Furthermore, among OAB symptoms score items, urge urinary incontinence was a risk factor for severe and moderate ED (p = 0.005). CONCLUSION: Aging and OAB (notably urinary urge incontinence) are risk factors for severe and moderate ED in men with LUTS. PMID- 26550920 TI - Time to Reassess Blood-Pressure Goals. PMID- 26550922 TI - Erratum. AB - Alison M Dines, David M Wood, Christopher Yates, Fridtjof Heyerdahl, Knut Erik Hovda, Isabelle Giraudon, Roumen Sedefov, and Paul I Dargan, Euro-Den Research Group. (2015) Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN) Clinical Toxicology, 53 (09), pp. 893 900.http://10.3109/15563650.2015.1088157 When the above article was first published online the Euro-DEN Research Group contributors were not listed correctly. This has now been corrected in the online version. Taylor & Francis apologises for this error. PMID- 26550921 TI - Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists. AB - Human precision-cut lung slices (hPCLSs) provide a unique ex vivo model for translational research. However, the limited and unpredictable availability of human lung tissue greatly impedes their use. Here, we demonstrate that cryopreservation of hPCLSs facilitates banking of live human lung tissue for routine use. Our results show that cryopreservation had little effect on overall cell viability and vital functions of immune cells, including phagocytes and T lymphocytes. In addition, airway contraction and relaxation in response to specific agonists and antagonists, respectively, were unchanged after cryopreservation. At the subcellular level, cryopreserved hPCLSs maintained Ca(2+)-dependent regulatory mechanisms for the control of airway smooth muscle cell contractility. To exemplify the use of cryopreserved hPCLSs in smooth muscle research, we provide evidence that bitter-taste receptor (TAS2R) agonists relax airways by blocking Ca(2+) oscillations in airway smooth muscle cells. In conclusion, the banking of cryopreserved hPCLSs provides a robust bioassay for translational research of lung physiology and disease. PMID- 26550923 TI - Observational Study on Less Invasive Surfactant Administration (LISA) in Preterm Infants<29 Weeks--Short and Long-term Outcomes. AB - BACKGROUND: A recent trial has demonstrated short-term benefits of a new minimal invasive procedure of surfactant administration in spontaneously breathing preterm infants >= 26 weeks (less invasive surfactant administration, LISA). AIM: To assess safety as well as short- and long-term outcomes of the LISA procedure in preterm infants between 23-28 weeks of gestation. STUDY DESIGN: Preterm infants born between 23+0 and 28+6 weeks gestational age during 2 periods, 18 months before (Period 1, n=44) and 18 months after introduction of LISA (Period 2, n=53), were analyzed for neonatal outcomes. 52% of discharged infants were assessed for neurodevelopmental outcome at corrected age of 3 years. RESULTS: In Period 2, 66% of the preterm infants needing surfactant were treated by the new method of LISA. In this period, fewer patient had to be ventilated during the first 3 days of life (42 vs. 77%, p<0.0005) and overall (55 vs. 77%, p=0.02). The median duration of mechanical ventilation was 2 vs. 3 days (p=0.056). Survival without BPD was 68% in period 1 and 74% in period 2 (p=0.29). In period 2, fewer infants received antibiotics after the third day of life (43 vs. 66%, p=0.04), systemic glucocorticoids were less frequently used (7.5 vs. 23%, p=0.04), and more infants received doxapram (34 vs. 2.3%, p<0.0001). Mental Developmental Index (89 vs. 98, p=0.16) and Physical Developmental Index (83 vs. 91, p=0.03) at 3 years improved between the 2 periods. CONCLUSION: Implementation of the LISA method on a neonatal ward was safe and feasible and was associated with less need for mechanical ventilation in infants >24 weeks. As our study was retrospective the observed trends for better pulmonary and neurocognitive outcomes should be interpreted with caution until results from randomized trials on the LISA procedure are available. PMID- 26550925 TI - Implant Placement in Failed Endodontic Sites: A Review. AB - Dental implants may fail to osseointegrate in sites of endodontic failure. This may occur as a result colonization by various anaerobic and facultative bacterial species. If an implant is placed in a site where vegetative bacteria are residing, the implant may fail to integrate if a bacterial colonization proceeds coronally. If the implant apical cortical bone is thin or if there is an apical fenestration, the colonization may proceed through the thin or nonexistent bone through the covering mucosa, relieving inflammatory pressure to create an apical (retrograde) peri-implantitis. Enterococcus faecalis may be the prime culprit in these types of implant failures. After thorough debridement, the implant may be immediately placed after extraction of an endodontically failed tooth, and the patient treated with an appropriate antibiotic. Alternatively waiting for postextraction healing and subsequent implant placement can be done. Nevertheless, either way may allow for the formation of bacterial vegetative forms or biofilms. The implant surface may be colonized when the surface is exposed to the bacteria. Thorough debridement is crucial. Nonetheless, organisms may persist. Randomized controlled trials are needed to elucidate this issue. PMID- 26550924 TI - Disorder-specific and shared neurophysiological impairments of attention and inhibition in women with attention-deficit/hyperactivity disorder and women with bipolar disorder. AB - BACKGROUND: In adults, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) have certain overlapping symptoms, which can lead to uncertainty regarding the boundaries of the two disorders. Despite evidence of cognitive impairments in both disorders separately, such as in attentional and inhibitory processes, data on direct comparisons across ADHD and BD on cognitive neurophysiological measures are as yet limited. METHOD: We directly compared cognitive performance and event-related potential measures from a cued continuous performance test in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. RESULTS: The NoGo-N2 was attenuated in women with BD, reflecting reduced conflict monitoring, compared with women with ADHD and controls (both p < 0.05). Both ADHD and BD groups showed a reduced NoGo-P3, reflecting inhibitory control, compared with controls (both p < 0.05). In addition, the contingent negative variation was significantly reduced in the ADHD group (p = 0.05), with a trend in the BD group (p = 0.07), compared with controls. CONCLUSIONS: These findings indicate potential disorder-specific (conflict monitoring) and overlapping (inhibitory control, and potentially response preparation) neurophysiological impairments in women with ADHD and women with BD. The identified neurophysiological parameters further our understanding of neurophysiological impairments in women with ADHD and BD, and are candidate biomarkers that may aid in the identification of the diagnostic boundaries of the two disorders. PMID- 26550926 TI - Clinical utility of serum samples for human parechovirus type 3 infection in neonates and young infants: The 2014 epidemic in Japan. AB - During the 2014 human parechovirus type 3 (HPeV3) epidemic in Niigata, Japan, this prospective observational study identified HPeV3 from 43/85 (51%) febrile young infants <4 months using PCR analysis of serum (n = 42) and/or cerebrospinal fluid (CSF) (n = 32) and genetic sequencing of the VP1 region of HPeV3. HPeV3 infected patients (median age, 32 days; range, 4-113 days) were diagnosed as having sepsis (79%), sepsis-like syndrome (19%), or encephalitis with septic shock (2%). Other than fever, mottled skin (67%) was significantly more frequent in HPeV3-infected patients than other virus-infected patients (P = 0.005). The rate of HPeV3 RNA detection in CSF without pleocytosis was high (88%; 28/32). Among the 32 patients whose serum and CSF samples were available, all patients were positive for serum PCR; however, 4 (12%) patients were negative for CSF PCR. Serum HPeV3 RNA level on admission was associated with younger age (P = 0.002), bad temper (P = 0.041), and grunting (P = 0.008). Among 6 patients with sequential data on serum HPeV3 RNA level, levels decreased rapidly without specific therapy. In conclusion, serum samples at disease onset are the most useful compared to CSF in detection of HPeV RNA and serum HPeV3 RNA level on admission was associated with important clinical manifestations in HPeV3-infected patients. PMID- 26550927 TI - Carboxymethyl lysine induces EMT in podocytes through transcription factor ZEB2: Implications for podocyte depletion and proteinuria in diabetes mellitus. AB - Advanced glycation end-products (AGEs) are implicated in the pathogenesis of diabetic nephropathy (DN). N-carboxymethyl-lysine (CML) is one of the predominant AGEs that accumulate in all renal compartments of diabetic patients. Nevertheless, the direct effect of CML on podocyte biology has not been explored. In this study, we demonstrate the induction of the transcription factor Zeb2 in podocytes upon exposure to CML through activation of NF-kB signaling cascade. Zeb2 orchestrates epithelial-mesenchymal transformation (EMT), during which cell cell and cell-extracellular matrix interactions are feeble and enable epithelial cells to become invasive. CML treatment induced both NF-kB and Zeb2 promoter activity and suppressed E-cadherin promoter activity. Inhibition of NF-kB activity prevented CML dependent induction of Zeb2 and loss of E-cadherin. While the exposure of podocytes to CML results in increased podocyte permeability, shRNA-mediated knockdown of Zeb2 expression abrogated CML-mediated podocyte permeability. Further, in vivo findings of elevated CML levels concurrent with increased expression of ZEB2 in glomeruli and proteinuria in diabetic rats confirm that CML-mediated manifestations in the kidney under chronic diabetes conditions. These in vitro and in vivo results envisage the novel axis of NFkB ZEB2 in podocytes playing a significant role in eliciting EMT and pathogenesis of DN. PMID- 26550928 TI - The tuberous sclerosis complex model Eker (TSC2+/-) rat exhibits hyperglycemia and hyperketonemia due to decreased glycolysis in the liver. AB - Tuberous sclerosis complex (TSC) presents as benign tumors that affect the brain, kidneys, lungs and skin. The inactivation of TSC2 gene, through loss of heterozygosity is responsible for tumor development in TSC. Since TSC patients are carriers of heterozygous a TSC2; mutation, to reveal the risk factors which these patients carry prior to tumor development is important. In this experiment, Eker rat which carry a mutation in this TSC2 gene were analyzed for their metabolic changes. Wild-type (TSC2+/+) and heterozygous mutant TSC2 (TSC2+/-) Eker rats were raised for 100 days. As a result, the Eker rats were found to exhibit hyperglycemia and hyperketonemia. However the high ketone body production in the liver was observed without accompanying increased levels of plasma free fatty acids or insulin. Further, production of the ketone body beta hydroxybutyrate was inhibited due to the low NADH/NAD(+) ratio resulting from the restraint on glycolysis, which was followed by inhibition of the malate-aspartate shuttle and TCA cycle. Therefore, we conclude that glycolysis is restrained in the livers of TSC2 heterozygous mutant rats, and these defects lead to abnormal production of acetoacetate. PMID- 26550930 TI - Intensity distribution analysis of cathodoluminescence using the energy loss distribution of electrons. AB - We present an intensity distribution analysis of cathodoluminescence (CL) excited with a focused electron beam in a luminescent thin film. The energy loss distribution is applied to the developed analysis method in order to determine the arrangement of the dipole locations along the path of the electron traveling in the film. Propagating light emitted from each dipole is analyzed with the finite-difference time-domain (FDTD) method. CL distribution near the film surface is evaluated as a nanometric light source. It is found that a light source with 30 nm widths is generated in the film by the focused electron beam. We also discuss the accuracy of the developed analysis method by comparison with experimental results. The analysis results are brought into good agreement with the experimental results by introducing the energy loss distribution. PMID- 26550929 TI - Untargeted metabolite profiling reveals that nitric oxide bioynthesis is an endogenous modulator of carotenoid biosynthesis in Deinococcus radiodurans and is required for extreme ionizing radiation resistance. AB - Deinococcus radiodurans (Drad) is the most radioresistant organism known. Although mechanisms that underlie the extreme radioresistance of Drad are incompletely defined, resistance to UV irradiation-induced killing was found to be greatly attenuated in an NO synthase (NOS) knockout strain of Drad (Deltanos). We now show that endogenous NO production is also critical for protection of Drad against gamma-irradiation (3000 Gy), a result of accelerated growth recovery, not protection against killing. NO-donor treatment rescued radiosensitization in Deltanos Drad but did not influence radiosensitivity in wild type Drad. To discover molecular mechanisms by which endogenous NO confers radioresistance, metabolite profiling studies were performed. Untargeted LC-MS-based metabolite profiling in Drad quantified relative abundances of 1425 molecules and levels of 294 of these were altered by >5-fold (p < 0.01). Unexpectedly, these studies identified a dramatic perturbation in carotenoid biosynthetic intermediates in Deltanos Drad, including a reciprocal switch in the pathway end-products from deoxydeinoxanthin to deinoxanthin. NO supplementation rescued these nos deletion associated changes in carotenoid biosynthesis, and fully-restored radioresistance to wildtype levels. Because carotenoids were shown to be important contributors to radioprotection in Drad, our findings suggest that endogenously-produced NO serves to maintain a spectrum of carotenoids critical for Drad's ability to withstand radiation insult. PMID- 26550932 TI - Appropriate Use Criteria for Coronary Revascularization and the Learning Health System: A Good Start. PMID- 26550931 TI - Single atom spectroscopy: Decreased scattering delocalization at high energy losses, effects of atomic movement and X-ray fluorescence yield. AB - Single atom localization and identification is crucial in understanding effects which depend on the specific local environment of atoms. In advanced nanometer scale materials, the characteristics of individual atoms may play an important role. Here, we describe spectroscopic experiments (electron energy loss spectroscopy, EELS, and Energy Dispersed X-ray spectroscopy, EDX) using a low voltage transmission electron microscope designed towards single atom analysis. For EELS, we discuss the advantages of using lower primary electron energy (30 keV and 60 keV) and higher energy losses (above 800 eV). The effect of atomic movement is considered. Finally, we discuss the possibility of using atomically resolved EELS and EDX data to measure the fluorescence yield for X-ray emission. PMID- 26550933 TI - Comments on the opinions published by Bergman et al. (2015) on Critical Comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals (Lamb et al., 2014). AB - Recently Bergman et al. (2015) took issue with our comments (Lamb et al., 2014) on the WHO-UNEP(1) report entitled the "State of the Science of Endocrine Disrupting Chemicals - 2012" (WHO 2013a). We find several key differences between their view and ours regarding the selection of studies and presentation of data related to endocrine disrupting chemicals (EDCs) under the WHO-IPCS(2) definition (2002). In this response we address the factors that we think are most important: 1. the difference between hazard and risk; 2. the different approaches for hazard identification (weight of the evidence [WOE] vs. emphasizing positive findings over null results); and 3. the lack of a justification for conceptual or practical differences between EDCs and other groups of agents. PMID- 26550934 TI - Characterizing the Hospice and Palliative Care Workforce in the U.S.: Clinician Demographics and Professional Responsibilities. AB - CONTEXT: Palliative care services are growing at an unprecedented pace. Yet, the characteristics of the clinician population who deliver these services are not known. Information on the roles, motivations, and future plans of the clinician workforce would allow for planning to sustain and grow the field. OBJECTIVES: To better understand the characteristics of clinicians within the field of hospice and palliative care. METHODS: From June through December 2013, we conducted an electronic survey of American Academy of Hospice and Palliative Medicine members. We queried information on demographics, professional roles and responsibilities, motivations for entering the field, and future plans. We compared palliative care and hospice populations alongside clinician roles using chi-square analyses. Multivariable logistic regression was used to identify predictors of leaving the field early. RESULTS: A total of 1365 persons, representing a 30% response rate, participated. Our survey findings revealed a current palliative care clinician workforce that is older, predominantly female, and generally with less than 10 years clinical experience in the field. Most clinicians have both clinical hospice and palliative care responsibilities. Many cite personal or professional growth or influential experiences during training or practice as motivations to enter the field. CONCLUSION: Palliative care clinicians are a heterogeneous group. We identified motivations for entering the field that can be leveraged to sustain and grow the workforce. PMID- 26550935 TI - Advance Care Discussions: Pediatric Clinician Preparedness and Practices. AB - CONTEXT: Few data exist regarding clinician preparedness to participate in advance care discussions (ACD) and the practices surrounding these discussions for children with life-threatening conditions. OBJECTIVES: We sought to understand pediatric clinician preparedness to participate in ACD and the practices surrounding these discussions. METHODS: A survey was administered to assess clinician attitudes and behaviors regarding ACD. RESULTS: Two hundred sixty-six clinicians (107 physicians and 159 nurses) responded to the survey (response rate 53.6%). Seventy-five percent of clinicians felt prepared to participate in ACD. Most clinicians believed they were prepared to express empathy (98.8%), discuss goals of care for an adolescent patient (90.3%), and elicit a parent's hopes (90.3%). Conversely, several felt unprepared to discuss resuscitation status with school-aged (59.7%) and adolescent (48.5%) patients and to conduct a family conference (39.5%). The most frequent topics addressed were: parents' understanding of the patient's illness (75.5%), primary goals of the parent (75.1%), and the parents' understanding of prognosis (71.1%). Conversely, the topics least commonly discussed were as follows: belief system of the patient/family (22.0%), patient's hopes (21.2%), and the patient's perceptions of his/her quality of life (19.8%). Notably, 40% of clinicians believe that caring for patients with poor prognoses is depressing, and this was more common among less-experienced clinicians (P = 0.048). CONCLUSION: Many clinicians believe they are prepared to participate in ACD, but practices are not consistent with expert recommendations for optimal ACD. Educational interventions aimed at improving clinician knowledge, attitudes, and behavior, and greater clinician support may enhance health care provider ACD preparedness and skills. PMID- 26550936 TI - Building Resiliency in a Palliative Care Team: A Pilot Study. AB - CONTEXT: Palliative care clinicians (PCCs) are vulnerable to burnout as a result of chronic stress related to working with seriously ill patients. Burnout can lead to absenteeism, ineffective communication, medical errors, and job turnover. Interventions that promote better coping with stress are needed in this population. OBJECTIVES: This pilot study tested the feasibility of the Relaxation Response Resiliency Program for Palliative Care Clinicians, a program targeted to decrease stress and increase resiliency, in a multidisciplinary cohort of PCCs (N = 16) at a major academic medical center. METHODS: A physician delivered the intervention over two months in five sessions (12 hours total). Data were collected the week before the program start and two months after completion. The main outcome was feasibility of the program. Changes in perceived stress, positive and negative affect, perspective taking, optimism, satisfaction with life, and self-efficacy were examined using nonparametric statistical tests. Effect size was quantified using Cohen's d. RESULTS: The intervention was feasible; all participants attended at least four of the five sessions, and there was no attrition. After the intervention, participants showed reductions in perceived stress and improvements in perspective taking. CONCLUSION: Our findings suggest that a novel team-based resiliency intervention based on elicitation of the relaxation response was feasible and may help promote resiliency and protect against the negative consequences of stress for PCCs. PMID- 26550937 TI - Symptom Clusters From Dialysis to Renal Transplantation: A Five-Year Longitudinal Study. AB - CONTEXT: Patients on dialysis experience multiple concurrent and often related symptoms defined as symptom clusters. Renal transplantation (RTX) is thought to reduce symptom experience and improve health-related quality of life. No longitudinal study has assessed symptoms and symptom clusters in patients in the transition from dialysis to RTX. OBJECTIVES: We aimed to assess changes in symptom prevalence, identify symptom clusters after RTX, and evaluate the effect of the treatment conversion on predefined symptom clusters. METHODS: A cohort of patients on chronic dialysis (n = 110) was followed prospectively with measurements of health-related quality of life using the Kidney Disease and Quality of Life-Short Form (KDQOL-SF) during dialysis (baseline) and after subsequent RTX. Predefined symptom clusters based on 11 symptoms listed in KDQOL SF were previously generated using principal component analysis with varimax rotation, that is, uremic (nausea, lack of appetite, dizziness, feeling squeezed out, shortness of breath, and chest pain), neuromuscular (numbness, sore muscle, and cramps), and skin (itching and dry skin) clusters. Stratified analyses were undertaken to identify characteristics associated with change in the symptom clusters after RTX. Cohen's d was used as effect size. RESULTS: Of the 110 patients, mean age was 51.3 +/- 14.4 years, and 66% were males. After RTX, the estimated glomerular filtration rate was 54 (interquartile range [IQR] 45-72) mL/minute/1.73 m2. Median follow-up time from assessments during dialysis was 55 (IQR 50-59) months, and follow-up time after RTX was 41 (IQR 34-51) months. The total symptom score improved (73 +/- 16 vs. 82 +/- 15, P = 0.001, and Cohen's d = 0.6), and the number of symptoms was reduced (6.5 +/- 2.6 vs. 4.7 +/- 3.0, P = 0.001). Seven symptoms improved statistically after RTX, but only two with Cohen's d > 0.5 (itching and cramps). The scores of the predefined symptom clusters improved after RTX: uremic (82 +/- 16 vs. 85 +/- 17, P = 0.008, and Cohen's d = 0.2), neuromuscular (66 +/- 24 vs. 79 +/- 18, P = 0.001, and Cohen's d = 0.6), and skin cluster (62 +/- 27 vs. 78 +/- 22, P = 0.001, and Cohen's d = 0.6). Symptom clusters could not be generated after RTX. CONCLUSION: Although symptoms and symptom clusters were reduced after RTX, the clinical relevance of the reductions was ambiguous. Symptom clusters could not be generated after RTX, suggesting that use of the KDQOL-SF may not be optimal to assess symptoms in RTX patients. PMID- 26550938 TI - The TDIF signaling network. AB - Plant growth and development are coordinately controlled by intercellular signaling molecules. CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION-related (CLE) peptides are crucial intercellular signaling molecules that control plant meristem maintenance. CLE peptides are perceived by plasma membrane-located receptor-like kinases, followed by the initiation of intracellular signaling cascades. Recent studies have uncovered these intracellular signaling networks involving signal divergence and integration. This review summarizes recent advances in the study of TDIF peptide signaling pathway, a representative model of CLE peptide signaling, focusing on newly uncovered biological functions and unique signal transduction mechanisms. PMID- 26550939 TI - The cytoskeleton in the pollen tube. AB - The cytoskeleton in pollen tubes has been intensively studied, because of its abundance and prominent roles and because the pollen tube is an excellent experimental system for cell biological studies. Pollen actin microfilaments (MFs) exist as multiple distinct populations, each participating in a specific cellular trafficking or organization process. Consequently, MFs are essential for pollen tube growth and are tightly regulated in response to various signals. Pollen microtubules (MTs) are non-essential and less characterized, but recent studies have implicated MTs in vesicle trafficking and cell wall construction in pollen tubes. This review summarizes recent advances in understanding the organization and regulation of both MFs and MTs and discusses their roles in cellular trafficking and the modulation of pollen-tube tip growth. PMID- 26550940 TI - Relating specific connexin co-expression ratio to connexon composition and gap junction function. AB - Cardiac connexin 43 (Cx43), Cx40 and Cx45 are co-expressed at distinct ratios in myocytes. This pattern is considered a key factor in regulating the gap junction channels composition, properties and function and remains poorly understood. This work aims to correlate gap junction function with the connexin composition of the channels at accurate ratios Cx43:Cx40 and Cx43:Cx45. Rat liver epithelial cells that endogenously express Cx43 were stably transfected to induce expression of accurate levels of Cx40 or Cx45 that may be present in various areas of the heart (e.g. atria and ventricular conduction system). Induction of Cx40 does not increase the amounts of junctional connexins (Cx43 and Cx40), whereas induction of Cx45 increases the amounts of junctional connexins (Cx43 and Cx45). Interestingly, the non-junctional fraction of Cx43 remains unaffected upon induction of Cx40 and Cx45. Co-immunoprecipitation studies show low level of Cx40/Cx43 heteromerisation and undetectable Cx45/Cx43 heteromerisation. Functional characterisation shows that induction of Cx40 and Cx45 decreases Lucifer Yellow transfer. Electrical coupling is decreased by Cx45 induction, whereas it is decreased at low induction of Cx40 and increased at high induction. These data indicate a fine regulation of the gap junction channel make-up in function of the type and the ratio of co-expressed Cxs that specifically regulates chemical and electrical coupling. This reflects specific gap junction function in regulating impulse propagation in the healthy heart, and a pro arrhythmic potential of connexin remodelling in the diseased heart. PMID- 26550941 TI - Comparison of cortical folding measures for evaluation of developing human brain. AB - We evaluated 22 measures of cortical folding, 20 derived from local curvature (curvature-based measures) and two based on other features (sulcal depth and gyrification index), for their capacity to distinguish between normal and aberrant cortical development. Cortical surfaces were reconstructed from 12 term born control and 63 prematurely-born infants. Preterm infants underwent 2-4 MR imaging sessions between 27 and 42weeks postmenstrual age (PMA). Term infants underwent a single MR imaging session during the first postnatal week. Preterm infants were divided into two groups. One group (38 infants) had no/minimal abnormalities on qualitative assessment of conventional MR images. The second group (25 infants) consisted of infants with injury on conventional MRI at term equivalent PMA. For both preterm infant groups, all folding measures increased or decreased monotonically with increasing PMA, but only sulcal depth and gyrification index differentiated preterm infants with brain injury from those without. We also compared scans obtained at term equivalent PMA (36-42weeks) for all three groups. No curvature-based measured distinguished between the groups, whereas sulcal depth distinguished term control from injured preterm infants and gyrification index distinguished all three groups. When incorporating total cerebral volume into the statistical model, sulcal depth no longer distinguished between the groups, though gyrification index distinguished between all three groups and positive shape index distinguished between the term control and uninjured preterm groups. We also analyzed folding measures averaged over brain lobes separately. These results demonstrated similar patterns to those obtained from the whole brain analyses. Overall, though the curvature-based measures changed during this period of rapid cerebral development, they were not sensitive for detecting the differences in folding associated with brain injury and/or preterm birth. In contrast, gyrification index was effective in differentiating these groups. PMID- 26550942 TI - Clinical characteristics and prognosis of mah-jong-induced epilepsy: A cohort review of 56 patients. AB - OBJECTIVE: The objective of this study was to investigate the clinical characteristics of reflex epilepsy elicited by playing mah-jong in Western China. METHODS: Consecutive patients with reflex epilepsy triggered by mah-jong from Jan 2011 to April 2014 were recruited at West China Hospital. Each patient underwent EEG recording and brain MRI scan. All clinical data were reviewed. Each patient had at least 12 months of follow-up. RESULTS: Fifty-six patients were included, with majority of them being male (52/56, 92.9%). Mean age was 43.9 +/- 10.0 years. Mean age at seizure onset was 35.1 +/- 16.3 years. Mean duration of reflex epilepsy was 4.0 +/- 2.2 years. The mean follow-up time was 32.0 +/- 13.2 months. Seventeen patients (30.4%) took antiepileptic drugs. Regardless of the medication, all 14 patients who avoided playing mah-jong reached seizure freedom, and 22 of the 42 patients (52.4%) who still played mah-jong continued to have seizures (p<0.05). CONCLUSIONS: Reflex epilepsy induced by mah-jong is a unique type of epilepsy in the Chinese population and usually occurs in adults after a long time lag of playing mah-jong. Avoiding the triggers is the most effective treatment for epilepsy. PMID- 26550943 TI - Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism. AB - Canavan disease (CD) is a neurological disorder caused by an interruption in the metabolism of N-acetylaspartate (NAA). Numerous mutations have been found in the enzyme that hydrolyzes NAA, and the catalytic activity of aspartoacylase is significantly impaired in CD patients. Recent studies have also supported an important role in CD for the enzyme that catalyzes the synthesis of NAA in the brain. However, previous attempts to study this enzyme had not succeeded in obtaining a soluble, stable and active form of this membrane-associated protein. We have now utilized fusion constructs with solubilizing protein partners to obtain an active and soluble form of aspartate N-acetyltransferase. Characterization of the properties of this enzyme has set the stage for the development of selective inhibitors that can lower the elevated levels of NAA that are observed in CD patients and potentially serve as a new treatment therapy. PMID- 26550944 TI - A score to predict the risk of emergency caesarean delivery in women with antepartum bleeding and placenta praevia. AB - OBJECTIVE: To identify antenatal events associated with emergency caesarean sections in women presenting with antepartum bleeding and placenta praevia and to establish a score to predict the risk of emergency caesarean after a first bleeding episode has resolved. STUDY DESIGN: This retrospective multicentre study included 250 women presenting with antepartum bleeding and placenta praevia from 20 weeks of gestation until term in three maternity units. The score was constructed from data from 163 women after identification of antenatal risk factors associated with emergency caesareans for profuse bleeding due to placenta praevia. It was validated on a second independent cohort of 87 women. RESULTS: Three variables were significantly associated with emergency caesareans: major or complete praevia, defined as complete or partial praevia (OR=33.15 (95% CI 4.3 257); p=0.001), occurrence of 3 or more episodes of antepartum of uterine bleeding (OR=2.53 (95% CI 1.1-5.86); p=0.03), and a first (sentinel) bleeding episode before 29 weeks of gestation (OR=2.64 (95% CI 1.17-5.98); p=0.02). A fourth variable, moderate or severe antepartum uterine bleeding, was significantly associated with emergency caesareans in the univariate but not the multivariate analysis (p=0.006). These four variables were incorporated into a weighted scoring system that included major praevia (4 points), three or more episodes of antepartum bleeding (3), first bleeding episode before 29 weeks of gestation (3), and bleeding episode estimated as moderate or severe (1). A score >=6/11 had a sensitivity of 83% and a specificity of 65% for predicting an emergency caesarean in the score development group and 95% and 62% in the validation group. CONCLUSION: A scoring system for placenta praevia with previous bleeding events, based on intensity, gestational age at sentinel bleed (before 29 weeks), number of bleeding episodes (>=3) and type of praevia (major) might be helpful to guide obstetric management and especially to determine the need for admission. PMID- 26550945 TI - Use of vasopressin vs epinephrine to reduce haemorrhage during myomectomy: a randomized controlled trial. AB - OBJECTIVE: To compare the effectiveness and safety of vasopressin with epinephrine for reducing blood loss during laparoscopic myomectomy. STUDY DESIGN: Sixty patients undergoing laparoscopic myomectomy were allocated at random to receive either dilute vasopressin or epinephrine into the serosal and/or overlying myometrium, and just around the myoma. The surgeon was blinded to the group allocation. Blood loss, duration of surgery, degree of surgical difficulty, postoperative pain scores and complications were compared. RESULTS: Patient characteristics (e.g. age, body mass index, demographic data), number of myomas, and location and size of the largest myoma were similar between the two study groups. There were no differences in operative blood loss, operative time, subjective surgical difficulty or postoperative pain between the two groups. Transient and non-serious increases in systolic and diastolic blood pressure and heart rate following intra-operative intramyometrial and/or perimyometrial injection of the vasoconstrictive agent only occurred in the epinephrine group, but the difference between the groups was not significant (13% vs 0%, p=0.112). No significant postoperative complications were observed in either group. CONCLUSIONS: Injection of dilute epinephrine before laparoscopic myomectomy was comparable to injection of dilute vasopressin in terms of operative blood loss, operative time, subjective surgical difficulty, postoperative pain and complications. PMID- 26550946 TI - The effects of TRIM5alpha polymorphism on HIV-2ROD and SIVmac239 replication in PBMCs from Chinese rhesus macaques and Vietnamese-origin cynomolgus macaques. AB - Because of the difficulty of obtaining Indian-origin rhesus macaques, Chinese origin rhesus macaques (CR) and Vietnamese-origin cynomolgus macaques (CM) are now used frequently in HIV/AIDS research. Nonetheless, the effects of TRIM5alpha polymorphism on viral replication in both CR and CM are unclear. To address these questions, we recruited 70 unrelated CR and 40 unrelated CM and studied the effect of TRIM5alpha polymorphism on HIV-2ROD and SIVmac239 replication in PBMCs. We found that 3 polymorphisms, located in the B30.2 domain of CR TRIM5alpha formed a haplotype and affected HIV-2ROD replication. In addition, we found that the variant Y178H, located in the Coiled-coil domain of CM TRIM5alpha, affected TRIM5alpha-mediated HIV-2ROD restriction. Finally, two polymorphisms, located in the Coiled-coil domain, altered anti-SIVmac239 activity in CR. We concluded that, CM TRIM5alpha polymorphism could alter HIV-2ROD infection; however, a different domain of CR TRIM5alpha was responsible for restricting different virus replication. PMID- 26550948 TI - Experimental infection of peridomestic mammals with emergent H7N9 (A/Anhui/1/2013) influenza A virus: Implications for biosecurity and wet markets. AB - During 2013, a novel avian-origin H7N9 influenza A virus (IAV) emerged in China and subsequently caused large economic and public health burdens. We experimentally infected three common peridomestic wild mammals with H7N9 (A/Anhui/1/2013) IAV. Striped skunks exhibited the highest burden of disease followed by raccoons and cottontail rabbits. Striped skunks also produced the highest levels of viral shedding (up to 10(6.4)PFU/mL nasal flush) followed by cottontail rabbits (up to 10(5.8)PFU/mL nasal flush) and raccoons (up to 10(5.2)PFU/mL nasal flush). Thus, various mammalian species, especially those that are peridomestic, could play a role in the epidemiology of emergent H7N9 IAV. Mammals should be accounted for in biosecurity plans associated with H7N9 and their presence in wet markets, dependent on species, could lead to increased transmission among interspecific species aggregations and may also pose an elevated zoonotic disease risk to visitors and workers of such markets. PMID- 26550947 TI - Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode. AB - Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. PMID- 26550949 TI - Glycyrrhizin attenuates isoflurane-induced cognitive deficits in neonatal rats via its anti-inflammatory activity. AB - Children exposed to general anesthetics such as isoflurane are maybe at an increased risk of cognitive impairment. Recent studies have indicated that this kind of cognitive decline is associated with neuroinflammation in the hippocampus of neonatal rodents. Glycyrrhizin is a naturally available compound for the treatment of inflammatory and neurodegenerative diseases. We therefore aimed to investigate the effects of glycyrrhizin on the isoflurane-induced cognitive deficits and hippocampal neuroinflammation in the neonatal rats. Seven day-old rats were exposed to 1.8% isoflurane for 4h. Saline and glycyrrhizin solution was injected intraperitoneally 30min prior to isoflurane or control gas exposure. The effects of isoflurane and glycyrrhizin treatment on memory performance were examined using Morris Water Maze (MWM) task. The protein expression of high mobility group box 1 (HMGB1), NFkappaB, Bcl-2, Bax and cleaved (active) caspase-3 were determined by Western blot assay. The protein levels of TNF-alpha and IL 1beta were detected by enzyme-linked immunosorbent assay (ELISA). The combination of ELISA and Western blot results showed that glycyrrhizin attenuated isoflurane induced increases of pro-inflammatory cytokines (TNF-alpha and IL-1beta) and activation of HMGB1/NFkappaB signaling pathway in the hippocampus of neonatal rats. Furthermore, glycyrrhizin treatment prevented the deficits in spatial memory induced by neonatal exposure to isoflurane. Consistent with these observations, we found that glycyrrhizin alleviated isoflurane-induced neuroapoptosis and down-regulations of PSD-95 and SNAP-25 in the hippocampus of neonatal rats. These results suggest that glycyrrhizin may be a potential therapeutic agent for developmental neurotoxicity and subsequent cognitive decline induced by neonatal exposure to general anesthetics. PMID- 26550950 TI - Event-related brain responses while listening to entire pieces of music. AB - Brain responses to discrete short sounds have been studied intensively using the event-related potential (ERP) method, in which the electroencephalogram (EEG) signal is divided into epochs time-locked to stimuli of interest. Here we introduce and apply a novel technique which enables one to isolate ERPs in human elicited by continuous music. The ERPs were recorded during listening to a Tango Nuevo piece, a deep techno track and an acoustic lullaby. Acoustic features related to timbre, harmony, and dynamics of the audio signal were computationally extracted from the musical pieces. Negative deflation occurring around 100 milliseconds after the stimulus onset (N100) and positive deflation occurring around 200 milliseconds after the stimulus onset (P200) ERP responses to peak changes in the acoustic features were distinguishable and were often largest for Tango Nuevo. In addition to large changes in these musical features, long phases of low values that precede a rapid increase - and that we will call Preceding Low Feature Phases - followed by a rapid increase enhanced the amplitudes of N100 and P200 responses. These ERP responses resembled those to simpler sounds, making it possible to utilize the tradition of ERP research with naturalistic paradigms. PMID- 26550951 TI - Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection. AB - Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA. Sprague-Dawley rats were fed with a diet rich in omega-3 PUFA during 10 days before myocardial infarction (MI). Two days before MI, rats received a daily dose of Meloxicam, an inhibitor of cyclooxygenase-2, PD146176, an inhibitor of 15-lipoxygenase, both inhibitors or vehicle. MI was induced by the occlusion of the left coronary artery for 40min followed by reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion while caspase-3, -8 and Akt activities were assessed at 30min of reperfusion. Rats receiving inhibitors, alone or in combination, showed a larger infarct size than those receiving omega-3 PUFA alone. Caspase-3 and -8 activities are higher in ischemic areas with inhibitors while Akt activity is diminished in groups treated with inhibitors. Moreover, the study showed that RvD1 restores cardioprotection when added to the inhibitors. Results from this study indicate that the inhibition of the metabolism of Omega-3 PUFA attenuate their cardioprotective properties. Then, resolvins seem to be an important mediator in the cardioprotection conferred by omega-3 PUFA in our experimental model of MI. PMID- 26550953 TI - Created unequal: Temporal dynamics of modal and amodal boundary interpolation. AB - In this study we manipulate the distribution of contrast polarity reversals in inducing configurations to create novel variants of modal and amodal completion. The novel variants, better equated in their geometric and photometric characteristics offer a superior way to probe similarities and differences in the temporal dynamics that underlie different forms of perceptual completion. We use dot localisation to directly compare the spatial characteristics of modally and amodally interpolated contours at presentation durations ranging from 120 to 300ms and find robust differences in the spatiotemporal formation of modally and amodally completed boundaries. Modally completed contours are localised more accurately and with better spatial precision across all presentation durations. Our results challenge the assumption that the boundary interpolation system depends solely on the geometrical relatability of inducing fragments and suggest that boundary interpolation depends on the spatial distribution of local luminance relationships. As an alternative to the strong version of the identity hypothesis, we propose that modal and amodal completion are mediated by different mechanisms, triggered by particular configurations of contrast polarity. PMID- 26550952 TI - Bromo-honaucin A inhibits osteoclastogenic differentiation in RAW 264.7 cells via Akt and ERK signaling pathways. AB - Osteoclasts are unique bone remodeling cells derived from multinucleated myeloid progenitor cells. They play homeostatic vital roles in skeletal modeling and remodeling but also destroy bone masses in many pathological conditions such as osteoporosis and rheumatoid arthritis. Receptor activation of NF-kappaB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of bromo-honaucin A (Br-H A) isolated from Leptolyngbya crossbyana (cyanobacterium). To investigate the mechanism of the inhibitory effect of Br-H A on osteoclastogenesis, we employed Br-H Ain RANKL-treated murine monocyte/macrophage RAW 264.7 cells for osteoclastic differentiation in-vitro. The inhibitory effects on in-vitro osteoclastogenesis was evaluated by counting the number of Tartarate resistant acid phospatase (TRAP) positive multinucleated cells and by measuring the expression level of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), cathepsin K (CATH K), GRB2-associated-binding protein 2 (GAB2), c-terminal myc kinase (C-MYC), C-terminal Src kinase (C-SRC) and Microphthalmia-associated transcription factor (MITF). Moreover, Br-H A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Finally, Br-H A clearly decreased the expression of Akt and also decreased the activation of ERK. Thus, the study identifies Br-H A as potent inhibitor potentialin the treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone degradation. PMID- 26550954 TI - Tilt aftereffect due to adaptation to natural stimuli. AB - The human visual system continuously adjusts to the current environment. To investigate these adjustments, biases in observers' perceptions owing to changes in the visual environment are measured (visual aftereffects). Typically, the stimuli used are synthetic and are composed of oriented patterns such as lines or gratings. These patterns are known to activate individual neurons in the visual cortex, but cover only a small subset of actual visual stimulations. To overcome this drawback, recent research has focused on synthetic patterns that mimic several aspects of natural stimulation. However, the aftereffects of natural stimulation per-se remain largely unexplored. Here, we interleaved presentations of unmodified natural image adaptors, selected according to criteria favoring content at a particular orientation, with presentations of targets that test a perceived orientation. This allowed us to measure the change in the perceived orientation, namely the tilt aftereffect (TAE), which resulted from repeated image presentations. Results show a close to standard TAE with adaptor durations around 500ms, which is reduced with longer presentations. Importantly, our method can be generalized to investigate other aftereffects by selecting images differently. PMID- 26550956 TI - Does executive function mediate the path from mothers' depressive symptoms to young children's problem behaviors? AB - This study investigated the mediation role played by children's executive function in the relationship between exposure to mild maternal depressive symptoms and problem behaviors. At ages 2, 3, and 6years, 143 children completed executive function tasks and a verbal ability test. Mothers completed the Beck Depression Inventory at each time-point, and teachers completed the Strengths and Difficulties Questionnaire at child age 6. Longitudinal autoregressive mediation models showed a mediation effect that was significant and quite specific; executive function (and not verbal ability) at age 3 mediated the path between mothers' depressive symptoms (but not general social disadvantage) at the first time-point and children's externalizing and internalizing problems at age 6. Improving children's executive functioning might protect them against the adverse effects of exposure to maternal depressive symptoms. PMID- 26550955 TI - Transcriptional control of cell fate in the stomatal lineage. AB - The Arabidopsis stomatal lineage is a microcosm of development; it undergoes selection of precursor cells, asymmetric and stem cell-like divisions, cell commitment and finally, acquisition of terminal cell fates. Recent transcriptomic approaches revealed major shifts in gene expression accompanying each fate transition, and mechanistic analysis of key bHLH transcription factors, along with mathematical modeling, has begun to unravel how these major shifts are coordinated. In addition, stomatal initiation is proving to be a tractable model for defining the genetic and epigenetic basis of stable cell identities and for understanding the integration of environmental responses into developmental programs. PMID- 26550958 TI - Going to work ill: A meta-analysis of the correlates of presenteeism and a dual path model. AB - Interest in presenteeism, attending work while ill, has flourished in light of its consequences for individual well-being and organizational productivity. Our goal was to identify its most significant causes and correlates by quantitatively summarizing the extant research. Additionally, we built an empirical model of some key correlates and compared the etiology of presenteeism versus absenteeism. We used meta-analysis (in total, K = 109 samples, N = 175,965) to investigate the correlates of presenteeism and meta-analytic structural equation modeling to test the empirical model. Salient correlates of working while ill included general ill health, constraints on absenteeism (e.g., strict absence policies, job insecurity), elevated job demands and felt stress, lack of job and personal resources (e.g., low support and low optimism), negative relational experiences (e.g., perceived discrimination), and positive attitudes (satisfaction, engagement, and commitment). Moreover, our dual process model clarified how job demands and job and personal resources elicit presenteeism via both health impairment and motivational paths, and they explained more variation in presenteeism than absenteeism. The study sheds light on the controversial act of presenteeism, uncovering both positive and negative underlying mechanisms. The greater variance explained in presenteeism as opposed to absenteeism underlines the opportunities for researchers to meaningfully investigate the behavior and for organizations to manage it. (PsycINFO Database Record PMID- 26550957 TI - The role of nonverbal working memory in morphosyntactic processing by school-aged monolingual and bilingual children. AB - The current study examined the relationship between nonverbal working memory and morphosyntactic processing in monolingual native speakers of English and bilingual speakers of English and Spanish. We tested 42 monolingual children and 42 bilingual children between the ages of 8 and 10years matched on age and nonverbal IQ. Children were administered an auditory Grammaticality Judgment task in English to measure morphosyntactic processing and a visual N-Back task and Corsi Blocks task to measure nonverbal working memory capacity. Analyses revealed that monolinguals were more sensitive to English morphosyntactic information than bilinguals, but the groups did not differ in reaction times or response bias. Furthermore, higher nonverbal working memory capacity was associated with greater sensitivity to morphosyntactic violations in bilinguals but not in monolinguals. The findings suggest that nonverbal working memory skills link more tightly to syntactic processing in populations with lower levels of language knowledge. PMID- 26550959 TI - Body Awareness as an Important Target in Multidisciplinary Chronic Pain Treatment: Mediation and Subgroup Analyses. AB - BACKGROUND: The results of a recently performed randomized clinical trial showed that the effect of a multidisciplinary treatment of chronic pain patients on body awareness (BA), catastrophizing, and depression was improved by adding psychomotor therapy (PMT), an intervention targeting BA. No significant effects were found on quality of life and disability. The present follow-up study aimed to explore the relationship between improvements in BA and multidisciplinary chronic pain rehabilitation treatment outcome across treatment conditions and the possible mediating effect of BA between treatment conditions. Furthermore, the hypothesis that patients with low BA benefit more from PMT was investigated. METHODS: In total, 94 patients with chronic pain participated in a randomized clinical trial comparing multidisciplinary treatment as usual (TAU) with TAU plus PMT. Outcome variables were health-related quality of life, disability, and depression. Self-efficacy and catastrophizing were the process variables of treatment and the potential mediating factors in the relationship between BA and the outcome variables. The data were analyzed by linear mixed-model analysis. RESULTS: Improvements in BA were related to improvements in all outcome variables across treatment conditions. The relationships were partly mediated by self efficacy, catastrophizing, or both. In the regression model with depression as the outcome variable, the regression coefficient of treatment (ie, PMT vs. TAU) decreased by 34% and became nonsignificant when BA was added as a potential mediator. Patients with low BA seemed to benefit more from PMT than patients with high BA, especially on depression, BA, and catastrophizing. CONCLUSIONS: BA might be an important target of treatment to improve the multidisciplinary treatment outcome in chronic pain patients. Furthermore, PMT is an intervention that seems to provide its benefits through improving BA and may be especially beneficial for patients with low BA. PMID- 26550960 TI - Muscle Triggers as a Possible Source of Pain in a Subgroup of Tension-type Headache Patients? AB - OBJECTIVES: Tension-type headache (TTH) is a common condition but the underlying etiology is not understood. Episodic TTH may develop into chronic TTH, and some possible triggers may be involved in generation and maintenance. Nociceptive generators and hyperexcitable spots in neck and shoulder regions may to some degree contribute to TTH. The current paper highlights some of the possible triggers and associated pain mechanisms involved in TTH and discusses whether inhibition of these possible triggers may provide new treatment options. RESULTS: This paper presents possible pathophysiological factors in TTH, the role of muscle pain, and how referred pain from triggers can contribute to development, maintenance of sensitization, or both. Referred pain patterns from trigger points and associated muscle hyperalgesia seem to be clinically important factors. Damping the nociceptive peripheral drive may not only reduce the number of TTH attacks but may also prevent, delay the transition from episodic into more chronic TTH, or both. The role of muscle triggers in driving TTH is debated as the pathogenesis of such triggers is not fully understood. Furthermore, inhibiting the drive from the triggers does not consistently modulate TTH. DISCUSSION: Understanding the possible triggers in TTH, muscle hyperalgesia, and widespread pain sensitization, may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions. Currently, there is a striking difference between the clinical observational studies favoring the role of muscle triggers in TTH and the intervention studies generally not supporting the role of muscle triggers in TTH. PMID- 26550961 TI - Involvement of CCL3/CCR5 Signaling in Dorsal Root Ganglion in Remifentanil induced Hyperalgesia in Rats. AB - BACKGROUND: Several mechanisms of remifentanil-induced hyperalgesia in spinal cord mainly have been explained such as N-methyl-D-aspartate receptors activation, but the mechanism in dorsal root ganglion (DRG) is poorly understood. It has been reported that CCL3 may be a regulator in both inflammatory pain and hyperalgesia. In this paper we explored whether CCL3 and CCR5, the mainly receptor of CCL3, play a role in the remifentanil-induced hyperalgesia in DRG by using a rat model with remifentanil administration. MATERIALS AND METHODS: The von Frey test and hot plate test were performed to measure the different threshold to evaluate mechanical and thermal hyperalgesia. Real-time polymerase chain reaction and Western blot analysis were used to evaluate time course of CCL3 and CCR5 expression in DRG after remifentanil infusion. The changes of glial cells and the expression of CCL3 and CCR5 were detected by immunofluorescence assay. Finally, intrathecal injection of CCL3-neutralizing antibody and maraviroc, the CCR5 antagonists, were used sevoflurane to confirm the role of CCL3/CCR5 signaling in the rat model of remifentanil-induced hyperalgesia. RESULTS: Remifentanil infusion profoundly increased thermal and mechanical hyperalgesia from 2 to 48 hours according to paw withdrawal latency (PWL) and paw withdrawal thresholds (PWT) (mean+/-SD, hyperalgesia vs. control, 17.4+/-0.91 vs. 8.5+/-1.46 s; 20.1+/-0.32 vs. 9.6+/-0.5 g, n=8). Moreover, the expression of mRNAs and proteins of CCL3 and its receptor CCR5 in DRG were dramatically increased after remifentanil infusion as compared with the normal saline group. We also found that CCL3 and CCR5 were colocalized with glial cells or neurons. Furthermore, intrathecal injection of CCL3-neutralizing antibody (mean+/-SD, hyperalgesia vs. control, 17.4+/-0.91 vs. 8.5+/-1.46 s; 20.1+/-0.32 vs. 9.6+/-0.5 g, n=5) and maraviroc(mean+/-SD, hyperalgesia vs. control, 17.4+/-0.91 vs. 8.5+/ 1.46 s; 20.1+/-0.32 vs. 9.6+/-0.5 g, n=5) were able to suppress remifentanil related thermal and mechanical hyperalgesia according to behavioral test. CONCLUSIONS: The results highlighted the fact that CCL3 and its receptor CCR5 in DRG might contribute to remifentanil-induced hyperalgesia. Thus CCL3/CCR5 signaling may be further considered in the development of new therapeutic strategies. PMID- 26550962 TI - Radical Reactions of Alkyl 2-Bromo-2,2-difluoroacetates with Vinyl Ethers: "Omitted" Examples and Application for the Synthesis of 3,3-Difluoro-GABA. AB - Addition reactions of perfluoroalkyl radicals to ordinary or polyfluorinated alkenes have been frequently used to synthesize perfluoroalkylated organic compounds. Here ethyl/methyl 2-bromo-2,2-difluoroacetate, diethyl (bromodifluoromethyl)phosphonate, [(bromodifluoromethyl)sulfonyl]benzene, and ethyl 2-bromo-2-fluoroacetate were involved in Na2S2O4-mediated radical additions to vinyl ethers in the presence of alcohols to give difluoro or monofluoroacetyl substituted acetals or corresponding difluoromethylphosphonate- and (difluoromethylphenyl)sulfonyl-substituted alkyl acetals. This methodology has also been applied as a key step in the synthesis of hitherto unknown 3,3-difluoro GABA, completing the series of isomeric difluoro GABAs. Comparison of the pKa values of 3-fluoro- and 3,3-difluoro-GABA with that of the fluorine free parent compound showed that introduction of each fluorine lead to acidification of both the amino and the carboxyl functions by approximately one unit. PMID- 26550963 TI - Seasonal Variation in the Incidence of Late-onset Bleb-related Infection After Filtering Surgery in Japan: The Japan Glaucoma Society Survey of Bleb-related Infection Report 3. AB - PURPOSE: To investigate seasonal variations in the incidence of late-onset bleb related infection after filtering surgery in Japan and the relationship between season and other factors. PATIENTS AND METHODS: This multicenter, prospective study is part of a 5-year-long Japan Glaucoma Society survey of bleb-related infection. We analyzed 156 cases of first-time infections (106 men, 50 women) encountered over 5 years to determine the seasonal variation using the Roger test and the relationships between season, sex, and age by logistic regression analysis. RESULTS: We noted significant monthly seasonal variation in the incidence of infection, which was the highest in January and February (23 and 18 infections, respectively; P=0.018) and lowest from August to November (9, 9, 11, and 8 infections, in that order). Multiple logistic regression analysis revealed that infections were most frequent among women in spring (odds ratio, 8.43; P=0.005). Staphylococcus aureus and Streptococcus spp. infections were more frequent in warmer seasons than in winter. Less virulent species, namely, coagulase-negative Staphylococcus spp., Corynebacterium spp., and Enterococcus spp., were frequently detected in winter. Coagulase-negative Staphylococcus spp. and Haemophilus influenzae were more frequent in women and men, respectively. CONCLUSIONS: The incidence of late-onset bleb-related infection showed significant seasonal variation and sex differences. The climate in Japan may influence the incidence of bleb-related infection. Moreover, besides climate, physical activity level and lifestyle may contribute to the seasonal variation in the incidence and sex differences in the involved bacterial agents of bleb related infections in Japan. PMID- 26550964 TI - Persistence of Glaucoma Therapy and Visual Field Progression. AB - PURPOSE: To determine the association of visual field (VF) progression with medication persistence in a cohort on glaucoma therapy. PATIENTS AND METHODS: Pharmacy records were examined over 3 years for patients started on glaucoma monotherapy. A patient was persistent if a prescription was refilled for the same medication < 90 days after the previous prescription had lapsed; otherwise was nonpersistent. Only patients with > 5 reliable VFs within 1-year pretherapy and 6 year posttherapy were included. Progression was analyzed with pointwise linear regression and defined using 2 criteria: (A) >= 2 adjacent progressing points (slope P < 0.01) in 1 hemifield; and (B) >= 3 progressing points (slope P < 0.01). The mean number and mean slope of progressing points and the mean global slopes were determined. RESULTS: Of 1206 patient eyes (131 persistent, 1075 nonpersistent), 941 were excluded leaving 175 (47 persistent and 128 nonpersistent) for analysis. The mean follow-up durations were 59.3 +/- 10.9 and 58.2 +/- 9.7 months (P = 0.07) for persistent and nonpersistent eyes, respectively. Overall, 2/47 (4.3%) and 10/128 (7.8%) eyes progressed among persistent and nonpersistent patients, respectively (P = 0.52) using criterion A and 1/47 (2.1%) and 12/128 (9.4%; P = 0.19) eyes using criterion B. Mean number of progressing points (0.3 +/- 0.9 vs. 0.7 +/- 1.8; P = 0.17), mean slope of progressing points (-2.2 +/- 1.1 vs. -2.8 +/- 1.3 dB/y; P = 0.27), and mean global slope (0.7 +/- 0.5 vs. -0.1 +/- 0.8 dB/y; P = 0.07) were similar for persistent and nonpersistent patients, respectively. CONCLUSION: There were small but appreciable differences in VF progression rates between persistent and nonpersistent patient eyes on glaucoma drops, but differences were not significant. PMID- 26550966 TI - Bleb-like Finding Caused by Idiopathic Scleral Thinning in an Eye With Absolute Glaucoma. AB - PURPOSE: To evaluate a bleb-like finding in an eye with absolute glaucoma using anterior-segment optical coherence tomography (AS-OCT). METHODS: A 35-year-old woman complained of sudden-onset pain in the right eye. She had been diagnosed with keratitis at 1.5 years old and the onset of secondary glaucoma was identified at 13 years old. At the age of 26 years, transscleral contact diode laser cyclophotocoagulation therapy was performed, except for the upper quadrant, because scleral thinning was noted at that time. At the age of 35 years, she was blind in her right eye and corneal opacity and a bleb-like structure in the upper conjunctiva was seen with a slit-lamp examination. This bleb-like structure was removed surgically at bulbar exenteration, and the pathology was examined. RESULTS: AS-OCT showed a bleb-like internal structure with a single large empty space and thin scleral tissue and relatively thin walls with high optical density. Pathology indicated that the high optical density bleb wall was connective tissue. On AS-OCT, the internal surface of the empty space was very smooth, which matched the pathology. Histochemically, there were goblet cells, as in normal conjunctiva, but not in the conjunctiva over the aqueous space. CONCLUSIONS: AS-OCT images found that the intrableb structure was in good agreement with the pathology results; these conjunctival changes were very similar to those after a standard trabeculectomy. PMID- 26550965 TI - Comparison of Eye Drop Instillation Before and After Use of Drop Application Strips in Glaucoma Patients on Chronic Topical Therapy. AB - PURPOSE: To evaluate the impact of using drop application strips on eye drop instillation in glaucoma patients on chronic topical ocular hypotensive therapy. METHODS: A total of 72 patients with primary open-angle glaucoma with an uncorrected visual acuity of 3/60 or more, self-administering topical antiglaucoma medication for >1 year were evaluated. One eye of each patient was included in the study. Patients were instructed to instill 0.5% carboxymethyl cellulose drop in 1 eye. They were then instructed to instill the same drop using the drop application strips. RESULTS: Mean age of the patients included in the study was 50.39 +/- 12.04 years. Before assistance of drop application strips, 35 (48.61%) patients placed the drop into the eye without any contact of the dropper nozzle, and, after application of the drop application strips, 66 (91.67%) patients placed the drop in the eye without any contact (P=0.025). The number of patients putting the first drop of drug into the eye without spilling over the adenexae increased from 30 (41.67%) to 45 (62.5%) after application of the strip (P<0.001). The mean number of drops instilled to get 1 drop into the eye decreased from 2 +/- 0.95 to 1.56 +/- 0.78 when the drop application strip was used (P<0.001). CONCLUSIONS: Use of a drop application strip causes a significant decrease in contact of the eye drop bottle nozzle with the eyeball and eyelid, decreases the number of drops instilled to get 1 drop into the eye, and is associated with an overall improvement in eye drop instillation. PMID- 26550967 TI - Risk Factors of Disease Progression After Cataract Surgery in Chronic Angle closure Glaucoma Patients. AB - PURPOSE: To evaluate clinical risk factors of disease progression after cataract surgery using phacoemulsification with posterior chamber intraocular lens implantation, in eyes with chronic angle-closure glaucoma (CACG) and coexisting cataract. DESIGN: Retrospective study. METHODS: The data of 56 eyes of 45 CACG patients who had undergone uncomplicated phacoemulsification with posterior chamber intraocular lens implantation were retrospectively analyzed. Disease progression was defined as glaucomatous optic nerve change or visual field (VF) deterioration according to the European Glaucoma Society guideline. Correlations between VF progression and various preoperative and postoperative factors were determined by chi and independent t tests. Linear regression analysis [(odds ratio (OR)] was used to determine predictive risk factors for disease progression using univariate and multivariate analyses. RESULTS: The mean postoperative follow-up period was 45.13 +/- 17.54 (24 to 84) months. Fourteen eyes (25%) with cataracts diagnosed with CACG progressed after phacoemulsification, but the remaining 42 eyes (75%) did not. According to univariate analysis, disease progression was significantly associated with older age, more number of preoperative/postoperative antiglaucoma drugs, higher scores of preoperative pattern standard deviation, and lower scores of preoperative and postoperative visual field index (VFI) (P<0.05). Using multivariate analysis, a lower score of preoperative VFI (OR: 0.86, P=0.044) and lower postoperative intraocular pressure (IOP) reduction, which was not sustained below 20% less than the preoperative mean IOP, were significantly correlated with disease progression after cataract surgery (OR: 8.44, P=0.048). CONCLUSIONS: CACG patients with low preoperative VFI and high postoperative IOP are at risk for disease progression even after uncomplicated cataract surgery. PMID- 26550968 TI - Immunohistochemical Characterization of the Ectopic Epithelium Devoid of Goblet Cells From a Posttraumatic Iris Cyst Causing Mucogenic Glaucoma. AB - PURPOSE: Mucogenic glaucoma is an unusual form of secondary open-angle glaucoma caused by intracameral ectopic mucus-producing epithelium. To date, only 3 cases have been described in detail. Numerous goblet cells in the specimens indicated a possible conjunctival origin. We immunohistochemically characterized the implanted epithelium from an iris cyst responsible for mucogenic glaucoma. METHODS: A series of immunostaining analyses were performed on a sector iridectomy specimen derived from an eye with mucogenic glaucoma and a history of limbal penetrating injury. An iris cyst was present in the inferonasal quadrant of the right eye of a 58-year-old man. The anterior chamber was filled with hazy, translucent material, and the chamber angle was gonioscopically open. The cyst was resected due to medically uncontrollable high intraocular pressure. RESULTS: The ectopic epithelium was mostly positive for CK19, a corneal and conjunctival epithelial marker. Negative staining for MUC5AC, a secretory mucin, and positive staining for MUC1, a membrane-bound mucin, corroborated the absence of goblet cells. Ectopic epithelial cells were abundantly positive for CK15, a limbal basal cell marker, but there was patchy immunostaining of CK13, a conjunctival epithelial marker, and sparse labeling with CK12, a corneal epithelial marker. Immunostaining patterns of CK15, CK13, and CK12 were nearly mutually exclusive. CONCLUSIONS: The ectopic epithelium of an iris cyst causing mucogenic glaucoma was most likely to originate from limbal basal cells, which showed dual direction of differentiation toward both the conjunctival and corneal epithelia. The membrane-bound mucin may have caused mucogenic glaucoma in the absence of goblet cells. PMID- 26550969 TI - Intraocular Pressure Spike and Corneal Decompensation Following Selective Laser Trabeculoplasty in Patients With Exfoliation Glaucoma. AB - PURPOSE: To report 5 cases of intractable intraocular pressure (IOP) elevation and 2 cases of corneal failure in patients with exfoliation glaucoma after undergoing selective laser trabeculoplasty (SLT). METHODS: SLT was performed for the treatment of exfoliation glaucoma in 5 patients, all of whom subsequently developed significant IOP elevation within 1 to 5 weeks following treatment. Two patients went on to develop corneal endothelial failure requiring transplantation within 9 to 11 months. RESULTS: All 5 patients failed to respond adequately to topical antiglaucoma therapy and required trabeculectomy. Two patients required secondary implantation of a glaucoma drainage device. Two patients suffered significant endothelial injury requiring corneal transplantation (one receiving penetrating keratoplasty and another receiving Descemet stripping automated endothelial keratoplasty). CONCLUSIONS: Significant and persistent IOP spikes requiring surgical intervention following SLT are extremely rare, with only 1 other case series of 4 patients (all with heavily pigmented angles) reported in the literature. Exfoliation patients, and likely all patients with heavily pigmented angles, should be considered at higher risk for developing this complication. Corneal endothelial failure is similarly rare. Nine cases have been reported in the literature, none requiring corneal transplantation. Further clinical attention and research is needed to help elucidate what factors (both pressure-dependent and pressure-independent) may predispose patients to corneal changes following SLT. PMID- 26550970 TI - Obstructive Sleep Apnea and Retinal Nerve Fiber Layer Thickness: A Meta-analysis. AB - STUDY OBJECTIVES: The association between obstructive sleep apnea syndrome (OSAS) and retinal nerve fiber layer (RNFL) thickness has been examined in many studies. However, the findings are inconsistent. Our goal is to evaluate the association between OSAS and RNFL thickness by performing a meta-analysis. METHODS: We conducted a PubMed database search in November 2014 to identify studies on OSAS and RNFL. Reference lists of retrieved articles were also reviewed. A fixed effects model was used to compute the summary mean difference (MD). RESULTS: Six studies involving 1034 eyes were included in the meta-analysis. The overall combined MD of RNFL in OSAS patients compared with control participants was -2.03 um [95% confidence interval (CI), -3.67 to -0.4; P=0.01]. The overall combined MDs of RNFL thickness in relation to moderate OSAS and severe OSAS were -2.49 um (95% CI: -4.54 to -0.44; P=0.02) and -6.36 um (95% CI: -8.4 to -4.32; P<0.001). But no significant difference was observed in mild OSAS; the combined MD was 2.05 um (95% CI: -4.23 to 0.13; P=0.07). Association was also observed in OSAS and RNFL thickness of the inferior quadrant, with a combined MD of -3.31 um (95% CI: -6.19 to -0.42; P=0.02). CONCLUSIONS: This meta-analysis provides evidence that OSAS is associated with RNFL thickness. Furthermore, it was observed that the greater the severity of OSAS, the greater the loss of RNFL. Among the 4 quadrants observed, the most affected quadrant was the inferior quadrant, and the least affected was the temporal quadrant. OSAS may have an impact on changes in RNFL and therefore more attention should be paid to patients with this condition. PMID- 26550971 TI - Dual Endotemponade for Extensive Long-standing Cyclodialysis Using Sulcus-fixated Cionni Ring and PCIOL. AB - A young patient presented with visual acuity of hand movements only, unrecordable intraocular pressure, and total cataract after trauma 12 months ago. She reported failure to improve with conservative therapy as well as a direct cycloplexy elsewhere. After cleft localization on preoperative gonioscopy, ultrasound biomicroscopy (UBM), and intraoperative gonioscopy, a partial-thickness scleral flap was fashioned at the site of maximum cleft height. Following phacoaspiration, a multipiece intraocular lens was implanted in the sulcus; its haptics aligned to the axis with maximum height of cyclodialysis. A Cionni ring placed in sulcus was sutured to sclera under the flap to provide additional tamponading effect. Postoperative UBM and gonioscopy confirmed cleft closure. Normalization of intraocular pressure was found on repeated follow-ups till 1 year (12 to 14 mm Hg). UBM showed increase in sulcus diameter, and "double indentation sign" on the ciliary body. PMID- 26550972 TI - Effect of Axial Length on Macular Ganglion Cell Complex Thickness and on Early Glaucoma Diagnosis by Spectral-Domain Optical Coherence Tomography. AB - PURPOSE: To investigate the effects of the axial length (AL)-related ocular magnification on the thickness of the macular ganglion cell complex (mGCC), and the diagnostic accuracy of the built-in normative database of the spectral-domain optical coherence tomographic (SD-OCT) instrument for early glaucoma detection. METHODS: This retrospective study included 41 eyes with early primary open-angle glaucoma and 36 normal eyes. The mGCC thickness within a 20-degree circle, equivalent to a 6 mm diameter in the Gullstrand model eye, was measured in the SD OCT images. The magnification effect was corrected using Bennett formula, and the mGCC thickness within the actual 6 mm diameter circle was determined. RESULTS: In normal eyes, the inferior corrected mGCC was significantly correlated with the AL (beta=-0.40, P=0.028), but correction for the magnification reduced the correlation. In 38 nonhighly myopic eyes, the sensitivity and specificity of the SD-OCT's significance maps for distinguishing early glaucoma were 95.0% and 94.4% when using either the uncorrected or the corrected mGCC. In 39 highly myopic eyes, the diagnostic accuracy was lower when using the uncorrected mGCC thickness (sensitivity was 95.2% and specificity was 44.4%), and was not improved when using the corrected mGCC (81.0% and 61.1%, respectively). CONCLUSIONS: The inferior mGCC was thinner in eyes with longer AL. The accuracy of the diagnosis with the SD-OCT built-in normative database for early glaucoma was not improved significantly by the correction of the AL-associated magnification in highly myopic eyes. Evaluation of highly myopic eyes with the nonhighly myopic normative database can lead to misdiagnosis. PMID- 26550973 TI - Management of Elevated Intraocular Pressure Associated With Subluxated/Dislocated Lenses by Combining Trabeculectomy With Adjunctive Mitomycin C With Lensectomy, Vitrectomy, and Scleral Fixation of Intraocular Lens. AB - AIM: To evaluate the short-term outcomes of lensectomy, combined with vitrectomy, scleral-fixated intraocular lens (SFIOL), and trabeculectomy with adjunctive mitomycin C (MMC) in patients with subluxated/dislocated crystalline lenses with associated elevated intraocular pressure (IOP). MATERIALS AND METHODS: This retrospective case series included 51 eyes of 51 patients who underwent lensectomy, vitrectomy, and SFIOL combined with trabeculectomy with MMC between 2003 and 2012. The main outcome measures assessed were IOP, change in visual acuity, IOP-lowering medications, and the complications and reoperation rates. RESULTS: The most common etiology observed was blunt trauma in 35 eyes (68.6%). Glaucomatous optic neuropathy was detected in 13 eyes (25.49%) preoperatively. The IOP reduced significantly from a preoperative mean of 26.3+/-11.5 mm Hg to 13+/-4.6 mm Hg (P<0.001) at the final visit. The mean preoperative number of IOP lowering medications of 2.9+/-0.8 reduced to 0.3+/-0.7 at last follow-up (P<0.001). The best-corrected visual acuity (Snellens) improved significantly from 20/600 to 20/60 (P<0.001). Complete success defined as IOP<=21 mm Hg without medications was achieved in 93%+/-5% and 80%+/-13% at 1 and 2 years, respectively. Major postoperative complications included retinal detachment in one eye and SFIOL dislocation in another. CONCLUSIONS: The technique of combining SFIOLs with trabeculectomy with adjunctive MMC in the management of subluxated/dislocated lenses resulted in good IOP control and improvement in visual acuity. PMID- 26550974 TI - CYP1B1 and MYOC Mutations in Vietnamese Primary Congenital Glaucoma Patients. AB - PURPOSE: Primary congenital glaucoma (PCG, OMIM 231300), the most common glaucoma in infancy, is caused by developmental defects in the anterior chamber angle. The 3 implicated genes are cytochrome P450 family I subfamily B polypeptide 1 (CYP1B1), latent transforming growth factor beta-binding protein 2 (LTBP2), and myocilin (MYOC). In this study, we sought to determine CYP1B1 and MYOC sequence variations in a Vietnamese cohort of index cases with PCG and their families. METHODS: Thirty Vietnamese subjects with PCG and 120 normal Vietnamese subjects were recruited. PCG was defined by the presence of at least 2 of the following clinical manifestations: increased corneal diameter (>10 mm at birth), corneal edema, Haab's striae, optic disc changes, and absence of other ocular or systemic diseases associated with childhood glaucoma. The coding exons, intron and exon boundaries, and untranslated regions of CYP1B1 and MYOC genes were PCR amplified and subjected to bidirectional sequencing in all subjects. RESULTS: We identified 2 homozygous and 3 heterozygous CYP1B1 sequence alterations in our study subjects. Among the 5 mutations identified, 2 (p.H279L and p.L283F) were novel mutations, whereas 3 (p.A121_S122insDRPAFA, p.L107V, and p.V320L) had been previously reported in PCG cases. None of these mutations was observed in any of the 120 controls. Haplotypes generated with 6 non-disease-causing intragenic single nucleotide polymorphisms detected in CYP1B1 indicated that the most common haplotype in Vietnamese population is similar to that found in Chinese and Japanese. The genotype-phenotype correlation showed no significant difference between mutation and no-mutation groups for quantitative clinical features (presenting intraocular pressure, corneal diameter, number of surgeries performed, the cup-to-disc ratio) as well as for qualitative factors (bilateral cases, phenotype severity, and the prognosis) (P>0.05). CONCLUSIONS: Five out of 30 families with PCG (16.7%) had disease attributable to CYP1B1 alterations suggesting that CYP1B1 is not the major gene causing PCG in Vietnamese unlike in the case of Arab or Romany patients. This percentage is similar to that detected in studies of Japanese and Chinese patients with sporadic PCG. PCG has proven to be an ocular disease of genetic heterogeneity, calling for further studies to identify novel genes causing this disease. PMID- 26550975 TI - Segmental Analysis of Macular Layers in Patients With Unilateral Primary Open Angle Glaucoma. AB - PURPOSE: To measure the thicknesses of the inner layers of the macula in both eyes of patients with unilateral primary open-angle glaucoma (POAG) and compare them with normal control eyes. METHODS: This prospective, cross-sectional pilot study enrolled patients with unilateral POAG, who had visual field defect in only 1 eye, and controls with a normal eye examination. Horizontal and vertical B-scan images centered on the fovea were obtained using spectral domain optical coherence. Semiautomatic delineation and segmentation of the inner layers of the retina were performed to evaluate macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses. Mean, superior, inferior, nasal, and temporal inner macular layer thicknesses were compared between affected eyes, fellow eyes without visual field defect, and control eyes. RESULTS: Nineteen patients with unilateral POAG and 14 normal control eyes were enrolled. In the affected POAG eyes, thinning of the mRNFL, GCC, and GC-IPL layers on horizontal and vertical scans were significant when compared with controls (P<0.05), particularly on vertical scans (P<0.001). The mean regional macular GCC and GC-IPL were most severely thinned in the inferior and temporal perifoveal regions. The unaffected eye of patients with unilateral POAG showed significant thinning of the mRNFL only in the vertical scan when compared with normal controls (P<0.05). CONCLUSIONS: Spectral domain optical coherence tomography detected significant thinning of the mRNFL, GCC, and GC-IPL in the affected eyes of patients with unilateral POAG. Fellow eyes showed early structural changes only in the vertical mRNFL scans when compared with normal controls. PMID- 26550976 TI - Shared Care in Monitoring Stable Glaucoma Patients: A Randomized Controlled Trial. AB - PURPOSE: Comparing the quality of care provided by a hospital-based shared care glaucoma follow-up unit with care as usual. PATIENTS AND METHODS: This randomized controlled trial included stable glaucoma patients and patients at risk for developing glaucoma. Patients in the Usual Care group (n=410) were seen by glaucoma specialists. In the glaucoma follow-up unit group (n=405), patients visited the glaucoma follow-up unit twice followed by a visit to a glaucoma specialist. The main outcome measures were: compliance to the working protocol by glaucoma follow-up unit employees; difference in intraocular pressure between baseline and at >=18 months; and patient satisfaction. RESULTS: Glaucoma follow up unit employees closely adhered to the working protocol for the measurement of intraocular pressure, visual acuity and GDx (>=97.5% of all visits). Humphrey Field Analyzer examinations were not performed as frequently as prescribed by the working protocol, but more often than in the Usual Care group. In a small minority of patients that required back-referral, the protocol was disregarded, notably when criteria were only slightly exceeded. There was no statistically significant difference in changes in intraocular pressure between the 2 treatment groups (P=0.854). Patients were slightly more satisfied with the glaucoma follow up unit employees than with the glaucoma specialists (scores: 8.56 vs. 8.40; P=0.006). CONCLUSIONS: In general, the hospital-based shared care glaucoma follow up closely observed its working protocol and patients preferred it slightly over the usual care provided by medical doctors. The glaucoma follow-up unit operated satisfactorily and might serve as a model for shared care strategies elsewhere. PMID- 26550977 TI - Adherence With the Use of Target Intraocular Pressure for Glaucoma Patients in a Large University Practice. AB - PURPOSE: To determine how often glaucoma specialists set a target intraocular pressure (IOP) and how they respond when the target is not achieved. METHODS: We reviewed 250 randomly selected charts of glaucoma patients seen by 5 glaucoma specialists to identify whether a target IOP was specifically set and to detail the plan of action when the target was exceeded. RESULTS: A target IOP was present for at least 1 eye in 66% of patients (165/250). Among the patients of 5 physicians, the percentage with a target IOP for both eyes ranged from 90% to 34%. Half of eyes with no target had an explaining feature, whereas the other half did not. The study visit IOP exceeded the target in at least 1 eye in 29% (50/173) of patients. When the target was not met, 66% (33/50) had a notation of action taken, with no significant difference among physicians in whether any action was taken (P=0.64). The significant differences among the 5 physicians in the use of target IOP were potentially associated with patient demographic and clinical features, such as age, race, treatment intensity, and visual field damage, which differed among the 5 practices (all P<0.05). CONCLUSIONS: Target IOP was recorded in the large majority of patient charts, but its use varied by physician and patient characteristics. On nearly one third of visits, IOP exceeded the target, indicating the need for active decision-making and management changes. PMID- 26550978 TI - Long-term Surgical Outcomes of 180-Degree Suture Trabeculotomy in Korean Patients With Primary Congenital Glaucoma. AB - PURPOSE: To investigate the surgical outcomes of 180-degree suture trabeculotomy in Korean patients with primary congenital glaucoma (PCG). PATIENTS AND METHODS: This retrospective study included 21 eyes of 17 children with PCG who underwent 180-degree suture trabeculotomy as a first surgical procedure. Surgical success was defined as (1) an intraocular pressure (IOP)<22 mm Hg with or without medication; (2) no additional intraocular surgery; and (3) no evidence of progressive optic disc cupping. The main outcome measure was the success rate of 180-degree suture trabeculotomy. Secondary outcome measures were IOP, number of glaucoma medications, and occurrence of complications. RESULTS: Of the 21 eyes included, 18 (85.7%) were classified as having achieved success at the final visit (mean last follow-up or failure time, 54.91+/-45.68 mo). Median age at surgery was 11.97 months with mean IOP 29.8+/-9.6 mm Hg, on average of 1.52 medications. The mean IOP at the final visit was 16.9+/-5.6 mm Hg on an average of 0.38 medications. The surgical success rate of 180-degree suture trabeculotomy at 1, 3, and 5 years was 95.0%, 87.7%, and 78.9%, respectively (Kaplan-Meier analysis). Three eyes underwent second operations and the mean time to failure was 29.39+/-19.75 months. Hyphema was observed in 10 eyes, but it cleared up within 7.6 days. CONCLUSION: The 180-degree suture trabeculotomy performed for PCG had a significant IOP-lowering effect and caused no remarkable complications. PMID- 26550979 TI - Uveal Effusion: Clinical Features, Management, and Visual Outcomes in a Retrospective Case Series. AB - PURPOSE: To present the experience of a tertiary care ophthalmic institution in the assessment and management of uncommon causes of uveal effusion and related complications. MATERIALS AND METHODS: A retrospective chart review was conducted of 12 patients diagnosed with uveal effusion and managed at our institution between 1996 and 2012. The presenting features, investigations, management, and outcomes were analyzed for each case. RESULTS: The case series encompasses a variety of clinical conditions that cause uveal effusion including inflammatory, hydrostatic, and idiopathic mechanisms. Two thirds of the patients presented with secondary angle closure. Half of the patients had serous retinal detachment. Modern imaging techniques including ultrasound biomicroscopy and high-resolution magnetic resonance imaging were critical in making the diagnosis. Seven of the 12 patients responded to medical treatment and 4 required scleral surgery. Uveal effusions resolved in all patients after treatment. CONCLUSIONS: Uveal effusion is a complex and poorly understood clinical entity with significant visual morbidity and is caused by a range of ocular and systemic diseases. Effective management is critically dependent on the underlying cause. PMID- 26550980 TI - Outcomes of Nd: YAG Goniopuncture After Viscocanalostomy/Phacoviscocanalostomy. AB - PURPOSE: The aim of this study is to evaluate the safety and efficacy of laser goniopuncture (LGP) to lower intraocular pressure (IOP) post-viscocanalostomy (VC)/phacoviscocanalostomy (PVC). Outcomes include: IOP reduction from pre-LGP levels and the need for further topical antiglaucomatous medication or surgery. PATIENTS AND METHODS: A total of 541 eyes that underwent VC/PVC between 2009 and 2012, at the Stanley eye unit in Abergele were included in the study. INCLUSION CRITERIA: All patients who had LGP at any timepoint after VC/PVC when target IOP was not achieved +/- progression in visual field with at least 6 months of follow up data.Statistical analysis was performed on IOP values pre- and post-LGP, involving chi, Fischer exact, Mann-Whitney U, and Wilcoxon tests. A P-value of <0.05 was accepted as the level of significance. RESULTS: Of the 515 included eyes, 136 (26%) required LGP after a mean of 15.11+/-9.73 months after surgery (95% confidence interval, 13.46-16.76 mo), ranging from 1 to 42 months. LGP reduced IOP significantly from a mean of 22.92+/-5.80 to 17.08+/-5.30 mm Hg immediately for all eyes, a reduction of 5.84 mm Hg (or a 25% reduction) (P<0.0001). IOP significantly reduced in the VC group with a mean reduction of 7.60 mm Hg compared with 4.85 mm Hg in the PVC group immediately after the procedure (P=0.0038). LGP was required sooner in the VC group compared with PVC, 11.35 and 14.57 months, respectively (P=0.0393). A total of 69 (62%) eyes were commenced on topical IOP-lowering medications, mean 7.26+/-6.41 months after LGP. CONCLUSIONS: This study supports previous evidence that LGP enhances the IOP lowering success of VC/PVC. The advantages of LGP are that it is a minimally invasive clinic-based procedure with a low complication rate. PMID- 26550981 TI - Effect of Laser in Situ Keratomileusis on Schiotz, Goldmann, and Dynamic Contour Tonometric Measurements. AB - PURPOSE: To assess the effect of laser in situ keratomileusis (LASIK) on ocular rigidity and compare its effect on intraocular pressure (IOP) readings with Goldmann applanation tonometry (GAT), Schiotz indentation tonometry (ST), and dynamic contour tonometry (DCT). PATIENTS AND METHODS: Prospective, observational, single-masked study. Eighty-one patients who underwent myopic LASIK and 108 unoperated myopic control patients were included in the study. The IOP was measured using GAT, DCT, and ST. The coefficient of ocular rigidity (Ko) was obtained from the regression analysis of the 3 readings obtained with each weight of the ST. Linear multiple regression analysis was performed with dummy variables to assess the effects of age, central corneal thickness (CCT), and refractive surgery on measured IOP values. RESULTS: Age, CCT, and previous LASIK explained 39.41% of the IOP readings with GAT, 25.31% with DCT, and 3.28% with ST. LASIK caused a mean decrease of -2.51 mm Hg in IOP readings (P=0.000) with GAT, -1.29 mm Hg (P=0.036) with DCT, and no significant change in IOP readings with ST (P=0.299). Significant differences in the Ko were observed between the LASIK and control groups. The Ko values were unrelated to age and CCT in the LASIK and control groups. CONCLUSIONS: ST seems to be less affected by previous LASIK procedures. There is a difference in the ocular rigidity between the unoperated and LASIK eyes that is not correlated with the CCT. Therefore, ST seems to measure changes in the biomechanical behavior of corneas that underwent LASIK surgery. PMID- 26550982 TI - Assessing the Role of the Family/Support System Perspective in Patients With Glaucoma. AB - PURPOSE: To investigate the role of the family/friends support system for patients with glaucoma and their perspective on barriers to effective glaucoma management. METHODS: Six focus groups were conducted in 3 geographically and ethnically diverse areas of the United States (Los Angeles, CA; Rochester, MN; Durham, NC) that included 31 participants; 68% (21/31) were family members and friends of glaucoma patients with poor vision and 32% (10/31) were support system individuals of patients with good vision. Content analysis was used to identify important themes. Semiquantitative analysis was used to measure the frequency of each theme. RESULTS: A total of 134 relevant comments were made in the 6 focus groups and 72% of relevant comments were made by individuals providing support for patients with poor vision. Family members and friends mentioned the following areas of concern regarding patients' glaucoma care: patient education (19.4%), doctor-patient relationship (17.9%), their own lack of involvement in the patient's medical care (17.2%), frustration with glaucoma and with the patient (14.9%), patient dependency on caregivers (14.9%), patient frustration with the disease (10.4%), and sex differences in coping mechanisms (5.2%). CONCLUSIONS: Support system individuals tend to be minimally involved in the patient's glaucoma status and care. This is especially true for support system members of patients with glaucoma who maintain good vision and those who do not have any other personal experiences with difficulties from glaucoma. Many of these family members express an interest in acquiring more education about glaucoma and becoming more involved in the patient's glaucoma care. PMID- 26550983 TI - Polyethylenimine Interfacial Layers in Inverted Organic Photovoltaic Devices: Effects of Ethoxylation and Molecular Weight on Efficiency and Temporal Stability. AB - We report a comparative study of polyethylenimine (PEI) and ethoxylated polyethylenimine (PEIE) cathode buffer layers in high performance inverted organic photovoltaic devices. The work function of the indium-tin oxide (ITO)/zinc oxide (ZnO) cathode was reduced substantially (Deltaphi = 0.73-1.09 eV) as the molecular weight of PEI was varied from 800 g mol(-1) to 750 000 g mol(-1) compared with the observed much smaller reduction when using a PEIE thin film (Deltaphi = 0.56 eV). The reference inverted polymer solar cells based on the small band gap polymer PBDTT-FTTE (ITO/ZnO/PBDTT-FTTE:PC70BM/MoO3/Ag), without a cathode buffer layer, had an average power conversion efficiency (PCE) of 6.06 +/- 0.22%. Incorporation of a PEIE cathode buffer layer in the same PBDTT FTTE:PC70BM blend devices gave an enhanced performance with a PCE of 7.37 +/- 0.53%. In contrast, an even greater photovoltaic efficiency with a PCE of 8.22 +/ 0.10% was obtained in similar PBDTT-FTTE:PC70BM blend solar cells containing a PEI cathode buffer layer. The temporal stability of the inverted polymer solar cells was found to increase with increasing molecular weight of the cathode buffer layer. The results show that PEI is superior to PEIE as a cathode buffer layer in high performance organic photovoltaic devices and that the highest molecular weight PEI interlayer provides the highest temporal stability. PMID- 26550985 TI - In Situ Study on the Evolution of Multimodal Particle Size Distributions of ZnO Quantum Dots: Some General Rules for the Occurrence of Multimodalities. AB - Properties of small semiconductor nanoparticles (NPs) are strongly governed by their size. Precise characterization is a key requirement for tailored dispersities and thus for high-quality devices. Results of a careful analysis of particle size distributions (PSDs) of ZnO are presented combining advantages of UV/vis absorption spectroscopy, analytical ultracentrifugation, and small-angle X ray scattering (SAXS). Our study reveals that careful cross-validation of these different methods is mandatory to end up with reliable resolution. PSDs of ZnO NPs are multimodal on a size range of 2-8 nm, a finding that is not yet sufficiently addressed. In the second part of our work the evolution of PSDs was studied using in situ SAXS. General principles for the appearance of multimodalities covering a temperature range between 15 and 45 degrees C were found which are solely determined by the aging state indicated by the size of the medium-sized fraction. Whenever this fraction exceeds a critical diameter, a new multimodality is identified, independent of the particular time-temperature combination. A fraction of larger particles aggregates first before a fraction of smaller particles is detected. Fixed multimodalities have not yet been addressed adequately and could only be evidenced due to careful size analysis. PMID- 26550984 TI - Interpolated average CT for PET attenuation correction in different lesion characteristics. AB - OBJECTIVE: Previously we proposed using an interpolated average computed tomography (IACT) method as a low-dose alternate of cine average computed tomography (CACT) for PET attenuation correction (AC). This study aims to evaluate its performance for thoracic lesions with different characteristics in simulations and clinical patients. MATERIALS AND METHODS: We used the XCAT phantom to simulate noisy fluorine-18 fluorodeoxyglucose (18F-FDG) distribution with respiratory motion amplitudes of 2 and 3 cm. Average activity and attenuation maps represented static PET and CACT, respectively. IACT was generated by the end-inspiration and end-expiration phases of the attenuation maps (HCT-in and HCT-ex) using a deformable registration method. Spherical lesions with diameters of 10 and 20 mm with four target-to-background ratios (TBRs) were simulated at four different locations individually, including the lower left lung, lower right lung, middle right lung, and upper right lung. Five patients with a total of six thoracic lesions were recruited. They were scanned 1 h after 315-480 MBq F-FDG injection. Simulated and clinical PET sinograms were reconstructed with AC using (i) CACT, (ii) IACT, and (iii) helical computed tomography (HCTs). The TBRs and mean standardized uptake value were analyzed. RESULTS: Significant artifacts were observed in PET HCTs from visual assessment. For both simulation and clinical study, PET IACT was more similar to PET CACT in terms of TBRs and mean standardized uptake value. The differences between CACT/IACT and HCTs were more significant for lesions located at the lower lungs. CONCLUSION: The IACT is a robust and low-dose AC method for improved thoracic lesion localization and quantitation for a wide range of lesion characteristics. PMID- 26550986 TI - H2O Dissociation-Induced Aluminum Oxide Growth on Oxidized Al(111) Surfaces. AB - The interaction of water vapor with amorphous aluminum oxide films on Al(111) is studied using X-ray photoelectron spectroscopy to elucidate the passivation mechanism of the oxidized Al(111) surfaces. Exposure of the aluminum oxide film to water vapor results in self-limiting Al2O3/Al(OH)3 bilayer film growth via counter-diffusion of both ions, Al outward and OH inward, where a thinner starting aluminum oxide film is more reactive toward H2O dissociation-induced oxide growth because of the thickness-dependent ionic transport in the aluminum oxide film. The aluminum oxide film exhibits reactivity toward H2O dissociation in both low-vapor pressure [p(H2O) = 1 * 10(-6) Torr] and intermediate-vapor pressure [p(H2O) = 5 Torr] regimes. Compared to the oxide film growth by exposure to a p(H2O) of 1 * 10(-6) Torr, the exposure to a p(H2O) of 5 Torr results in the formation of a more open structure of the inner Al(OH)3 layer and a more compact outer Al2O3 layer, demonstrating the vapor-pressure-dependent atomic structure in the passivating layer. PMID- 26550987 TI - Clinical Application of Anti-CCR4 Monoclonal Antibody. AB - Mogamulizumab (KW-0761) is a humanized anti-CCR4 monoclonal antibody with a defucosylated Fc region (Potelligent(r) Technology), which markedly enhances antibody-dependent cellular cytotoxicity by increasing its binding affinity to the Fcx03B3; receptor expressed on effector cells. It is an effective agent for patients with CCR4-positive adult T-cell leukemia and peripheral T-cell lymphoma, for which no standard therapy exists, and it has an acceptable toxicity profile. In addition, because CCR4 is expressed on CD45RA-FOXP3highCD4+ effector regulatory T (Treg) cells, it is an even more attractive target, because Treg cells involved in the tumor escape from host immunity in the tumor microenvironment. Based on this concept, we conducted a clinical study of mogamulizumab for the treatment of CCR4-negative advanced or recurrent solid cancer, with the aim of depleting effector Treg cells and thus boosting anti cancer immune responses. In this study, mogamulizumab infusion at doses ranging from 0.1 to 1.0 mg/kg was safe and well tolerated. Four of 10 patients showed stable disease during treatment and showed long-term survival. Mogamulizumab efficiently depleted effector Treg cells even at the lowest dose of 0.1 mg/kg, and an augmentation or induction of specific immune responses to cancer/testis antigens was observed in some patients. In the near future, a novel immunotherapy targeting Treg cells with mogamulizumab will be offered to patients with different types of cancer. PMID- 26550988 TI - Defining the Genetic Architecture of Alzheimer's Disease: Where Next. AB - BACKGROUND: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. SUMMARY: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a significant proportion of genetic variation in disease pathology is yet to be detected. Rare variation is being investigated through exome chip and next-generation sequencing experiments, which have already identified new protective and risk variants. Using a polygenic risk score approach, it is now possible to identify population groups with the greatest and fewest biological susceptibilities to disease. This method has proved more effective in predicting disease status than individual, genome-wide significant variants of small/moderate effect. Future studies will establish the specific functional changes that contribute to disease by piloting novel cellular modelling techniques using reprogrammed induced pluripotent stem cells from individuals with selected risk profiles. This will allow a variety of models to be produced to help understand disease mechanisms and test new drug therapies. KEY MESSAGES: Alzheimer's disease is a polygenic trait that has been linked to deficits in immunity, endocytosis, cholesterol metabolism and ubiquitination. Future work will focus on identifying rare disease susceptibility loci, unpicking the functional significance of the known risk loci and piloting novel cellular modelling techniques. PMID- 26550989 TI - Pyruvate to Lactate Metabolic Changes during Neurodevelopment Measured Dynamically Using Hyperpolarized 13C Imaging in Juvenile Murine Brain. AB - Hyperpolarized 13C magnetic resonance imaging has recently been used to dynamically image metabolism in vivo. This technique provides the capability to investigate metabolic changes in mouse brain development over multiple time points. In this study, we used 13C magnetic resonance spectroscopic imaging and hyperpolarized 13C-1-labeled pyruvate to analyze its conversion into lactate. We also applied T2-weighted anatomical imaging to examine brain volume changes starting from postnatal day 18 (P18). We combined these results with body weight measurements for a comprehensive interpretation of mouse brain maturation. Both the produced lactate level and pyruvate to lactate conversion rate decreased with increasing age in a linear manner. Total brain volume remained the same after P18, even though body weight continued to grow exponentially. Our results have shown that the rate of metabolism of 13C-1 pyruvate to lactate in brain is high in the young mouse and decreases with age. The brain at P18 is still relatively immature and continues to develop even as the total brain volume remains the same. PMID- 26550990 TI - Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T. AB - For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 MUl and 27 MUl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli. PMID- 26550991 TI - DNA Methylation Patterns Can Estimate Nonequivalent Outcomes of Breast Cancer with the Same Receptor Subtypes. AB - Breast cancer has various molecular subtypes and displays high heterogeneity. Aberrant DNA methylation is involved in tumor origin, development and progression. Moreover, distinct DNA methylation patterns are associated with specific breast cancer subtypes. We explored DNA methylation patterns in association with gene expression to assess their impact on the prognosis of breast cancer based on Infinium 450K arrays (training set) from The Cancer Genome Atlas (TCGA). The DNA methylation patterns of 12 featured genes that had a high correlation with gene expression were identified through univariate and multivariable Cox proportional hazards models and used to define the methylation risk score (MRS). An improved ability to distinguish the power of the DNA methylation pattern from the 12 featured genes (p = 0.00103) was observed compared with the average methylation levels (p = 0.956) or gene expression (p = 0.909). Furthermore, MRS provided a good prognostic value for breast cancers even when the patients had the same receptor status. We found that ER-, PR- or Her2- samples with high-MRS had the worst 5-year survival rate and overall survival time. An independent test set including 28 patients with death as an outcome was used to test the validity of the MRS of the 12 featured genes; this analysis obtained a prognostic value equivalent to the training set. The predict power was validated through two independent datasets from the GEO database. The DNA methylation pattern is a powerful predictor of breast cancer survival, and can predict outcomes of the same breast cancer molecular subtypes. PMID- 26550993 TI - Reply: To PMID 25658178. PMID- 26550992 TI - GsCML27, a Gene Encoding a Calcium-Binding Ef-Hand Protein from Glycine soja, Plays Differential Roles in Plant Responses to Bicarbonate, Salt and Osmotic Stresses. AB - Calcium, as the most widely accepted messenger, plays an important role in plant stress responses through calcium-dependent signaling pathways. The calmodulin like family genes (CMLs) encode Ca2+ sensors and function in signaling transduction in response to environmental stimuli. However, until now, the function of plant CML proteins, especially soybean CMLs, is largely unknown. Here, we isolated a Glycine soja CML protein GsCML27, with four conserved EF hands domains, and identified it as a calcium-binding protein through far-UV CD spectroscopy. We further found that expression of GsCML27 was induced by bicarbonate, salt and osmotic stresses. Interestingly, ectopic expression of GsCML27 in Arabidopsis enhanced plant tolerance to bicarbonate stress, but decreased the salt and osmotic tolerance during the seed germination and early growth stages. Furthermore, we found that ectopic expression of GsCML27 decreases salt tolerance through modifying both the cellular ionic (Na+, K+) content and the osmotic stress regulation. GsCML27 ectopic expression also decreased the expression levels of osmotic stress-responsive genes. Moreover, we also showed that GsCML27 localized in the whole cell, including cytoplasm, plasma membrane and nucleus in Arabidopsis protoplasts and onion epidermal cells, and displayed high expression in roots and embryos. Together, these data present evidence that GsCML27 as a Ca2+-binding EF-hand protein plays a role in plant responses to bicarbonate, salt and osmotic stresses. PMID- 26550994 TI - Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease. AB - Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Abeta(1-42) and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Abeta(1-42) levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Abeta(1-42) and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD. PMID- 26550995 TI - Changes in insulin sensitivity and secretion after sleeve gastrectomy. AB - BACKGROUND: Sleeve gastrectomy is indicated for the treatment of obesity and related co-morbidity including diabetes. The dynamic changes in insulin secretion and sensitivity after sleeve gastrectomy are unknown. METHODS: Whole-body insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique, and insulin secretion by C-peptide deconvolution after an oral glucose tolerance test (OGTT), before and 3, 6 and 12 months after sleeve gastrectomy in morbidly obese subjects. The time course of glucagon-like peptide (GLP) 1, as a marker of insulin secretion following OGTT, was also assessed. RESULTS: Ten patients were included in the study. Median (range) baseline insulin sensitivity (M-value) increased from 84.0 (20.2-131.4) mmol per kg per min at baseline to 122.8 (99.0 179.3) mmol per kg per min at 12 months after surgery (P = 0.015). Fasting insulin sensitivity, measured by homeostatic model assessment of insulin resistance, which represents a surrogate index of hepatic insulin resistance, decreased from 3.3 (1.9-5.5) to 0.7 (0.5-1.1) mg/dl . uunits/ml (P < 0.001). Total insulin secretion, measured as incremental area under the curve (AUC), after OGTT decreased from 360.4 (347.9-548.0) to 190.1 (10.1-252.0) mmol/l . 180 min at 12 months (P = 0.011). The AUC for GLP-1 increased from 258.5 (97.5-552.6) to 5531.8 (4143.0-7540.9) pmol/l . 180 min at 12 months after sleeve gastrectomy (P < 0.001). In multiple regression analysis, 51 per cent of the M-value variability was explained by GLP-1 secretion. CONCLUSION: Sleeve gastrectomy improved insulin sensitivity and reduced insulin secretion within 6 months after surgery. Although there was a correlation between insulin sensitivity and bodyweight, the major driver of the improvement in insulin sensitivity was GLP-1 secretion. PMID- 26550996 TI - Change in quality of life of people with dementia in residential care facilities: a 3-year follow-up study. PMID- 26550997 TI - Community-Level Social Capital and Psychological Distress among the Elderly in Japan: A Population-Based Study. AB - Despite accumulating evidence, previous studies have not clearly separated the contribution of community-level social capital on mental health from that of individual-level social support. We examined the association between community level social capital and psychological distress in a sample of older Japanese individuals, taking into account the effects of individual-level social capital and social support. We collected data via a cross-sectional survey among all residents aged >=65 in three rural municipalities in Okayama Prefecture. We measured two components of social capital in the questionnaire: perceptions of trust and reciprocity in the community. Community-level social capital was obtained by aggregating individual responses and calculating the proportion of subjects reporting mistrust and lack of reciprocity. Psychological distress was assessed by the Kessler Psychological Distress scale. We calculated rate ratios [corrected] (RRs) and 95% confidence intervals (CIs) for psychological distress using two-level Poisson regression models (9,761 individuals nested within 35 communities). The prevalence of psychological distress was 39.8%. Low community level social capital was associated with psychological distress, even after controlling for individual-level social support, age, sex, educational attainment, frequency of alcohol consumption, smoking status, body mass index, marital status, socioeconomic status, and number of cohabiters. The adjusted RRs per 10% increase of the proportion of mistrust and lack of reciprocity in the communities were 1.23 (95% CI: 1.01-1.51) and 1.12 (95% CI: 1.02-1.24), respectively. Lower levels of community-level social capital are associated with psychological distress among the Japanese elderly population, even after adjusting for individual-level perceptions of social capital and social support. PMID- 26550999 TI - Perioperative Blood Transfusion, Age at Surgery, and Prognosis in a Database of 526 Upper Gastrointestinal Cancers. AB - AIMS: It is demonstrated that older animals have significantly weaker responses to new alloantigen stimulation than young animals, but the effect on prognosis of perioperative blood transfusion in relation to patient age is unknown. This study is retrospective review to investigate the relationship between perioperative blood transfusion, age at surgery, and clinical outcome in upper gastrointestinal cancer patients. METHODS: We analyzed data of 526 upper gastrointestinal cancer patients who underwent curative resection from 2005 to 2010. RESULTS: In esophageal cancer patients, patients with blood transfusion experienced significantly shorter overall survival (OS; univariate HR 2.50, p = 0.0006) and disease-free survival (DFS; univariate HR 1.71, p = 0.016) than patients without. Similar results were observed in gastric cancer patients (OS; univariate HR 3.35, p = 0.0001 and DFS; univariate HR = 3.18, p < 0.0001). Furthermore perioperative blood transfusion may be an independent prognostic factor in esophageal cancer patients (multivariate HR = 2.07, p = 0.026). Interestingly, age at surgery significantly affected the influence of blood transfusion on patient outcome in esophageal cancer patients (p for interaction = 0.022). CONCLUSION: The negative effect of perioperative blood transfusion was particularly evident among younger patients with esophageal cancer. PMID- 26550998 TI - What Dyadic Reparation Is Meant to Do: An Association with Infant Cortisol Reactivity. AB - BACKGROUND: The latency to reparation of interactive mismatches (interactive repair) is argued to regulate infant distress on a psychobiological level, and maternal anxiety disorders might impair infant regulation. SAMPLING AND METHODS: A total of 46 dyads (19 mothers with an anxiety disorder, 27 controls) were analyzed for associations between interactive repair and infant cortisol reactivity during the Face-to-Face-Still-Face paradigm 3-4 months postpartum. Missing cortisol values (n = 16) were imputed. Analyses were conducted on both the original and the pooled imputed data. RESULTS: Interactive repair during the reunion episode was associated with infant cortisol reactivity (original data: p < 0.01; pooled data: p < 0.01) but not maternal anxiety disorder (p > 0.23). Additional stepwise regression analyses found that latency to repair during play (p < 0.01), an interaction between distress during the first trimester of pregnancy and latency to repair during reunion (p < 0.01) and infant self comforting behaviors during the reunion episode (p = 0.04) made independent contributions to cortisol reactivity in the final regression model. CONCLUSIONS: This is the first study demonstrating that interactive repair is related to infant psychobiological stress reactivity. The lack of a relation to maternal anxiety disorder may be due to the small sample size. However, this result emphasizes that infants respond to what they experience and not to the maternal diagnostic category. PMID- 26551000 TI - Vibrational Spectroscopic Observation of Atomic-Scale Local Surface Sites Using Site-Selective Signal Enhancement. AB - Molecule-substrate interactions are sensitively affected by atomic-scale surface structures. Unique activity in heterogeneous catalysts or electrocatalysts is often related with local surface sites with specific structures. We demonstrate that adsorption geometry of a model molecule with an isocyanide anchor is drastically varied among one-fold atop, two-fold bridge, and three-fold hollow configurations with increasing the size of atomic-scale local surface sites of Pd islands on an Au(111) model surface. The vibrational spectroscopic observation of such local information is realized by site-selective and self-assembled formation of hotspots, where Raman scattering intensity is significantly enhanced via excitation of localized surface plasmons. PMID- 26551001 TI - Overview: Cancer Stem Cell and Tumor Environment. AB - It is becoming clear that cancer cells display features of normal tissue organization in the microenvironment, where cancer stem cells (CSCs) can drive tumor growth in the tumor environment. It has been proposed that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and tumor heterogeneity. The concept of leukemia stem cells (LSCs) also becomes critical in understanding the pathogenesis of leukemia, and alterations in the bone marrow niche are commonly observed in blood malignancies and directly contribute to the aberrant function of disease-initiating LSCs. We describe the cutting-edge progress regarding LSC research and the promising clinical strategies with LSC-targeted therapy. PMID- 26551003 TI - Got It! Let's Cool It! But What's Next in Organ Donor Research? PMID- 26551002 TI - Tau Immunotherapy. AB - In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115 9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-beta (Abeta) pathology, greater clinical efficacy may be achieved by clearing tau than Abeta aggregates in the later stages of the disease, when cognitive impairments become evident. Substantial insight has now been obtained regarding which epitopes to target, mechanism of action and potential toxicity, but much remains to be clarified. All of these factors likely depend on the model/disease or stage of pathology and the immunogen/antibody. Interestingly, tau antibodies interact with the protein both extra- and intracellularly, but the importance of each site for tau clearance is not well defined. Some antibodies are readily taken up into neurons, whereas others are not. It can be argued that extracellular clearance may be safer but less efficacious than intraneuronal clearance and/or sequestration to prevent secretion and further spread of tau pathology. Development of therapeutic tau antibodies has led to antibody-derived imaging probes, which are more specific than the dye-based compounds that are already in clinical trials. Such specificity may give valuable information on the pathological tau epitope profile, which could then guide the selection of therapeutic antibodies for maximal efficacy and safety. Hopefully, tau immunotherapy will be effective in clinical trials, and further advanced by mechanistic clarification in experimental models with insights from biomarkers and postmortem analyses of clinical subjects. PMID- 26551004 TI - HybProbes-based real-time PCR assay for specific identification of Streptomyces scabies and Streptomyces europaeiscabiei, the potato common scab pathogens. AB - The aim of this study was to develop and validate a HybProbes-based real-time PCR assay targeting the trpB gene for specific identification of Streptomyces scabies and Streptomyces europaeiscabiei. Four primer pairs and a fluorescent probe were designed and evaluated for specificity in identifying S. scabies and Streptomyces europaeiscabiei, the potato common scab pathogens. The specificity of the HybProbes-based real-time PCR assay was evaluated using 46 bacterial strains, 23 Streptomyces strains and 23 non-Streptomyces bacterial species. Specific and strong fluorescence signals were detected from all nine strains of S. scabies and Streptomyces europaeiscabiei. No fluorescence signal was detected from 14 strains of other Streptomyces species and all non-Streptomyces strains. The identification was corroborated by the melting curve analysis that was performed immediately after the amplification step. Eight of the nine S. scabies and S. europaeiscabiei strains exhibited a unique melting peak, at Tm of 69.1 degrees C while one strain, Warba-6, had a melt peak at Tm of 65.4 degrees C. This difference in Tm peaks could be attributed to a guanine to cytosine mutation in strain Warba-6 at the region spanning the donor HybProbe. The reported HybProbes assay provides a more specific tool for accurate identification of S. scabies and S. europaeiscabiei strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports a novel assay based on HybProbes chemistry for rapid and accurate identification of the potato common scab pathogens. Since the HybProbes chemistry requires two probes for positive identification, the assay is considered to be more specific than conventional PCR or TaqMan real-time PCR. The developed assay would be a useful tool with great potential in early diagnosis and detection of common scab pathogens of potatoes in infected plants or for surveillance of potatoes grown in soil environment. PMID- 26551005 TI - Clinical Implications of TbetaRII Expression in Breast Cancer. AB - OBJECTIVE: To explore the relationship between TbetaRII [type II TGFbeta (transforming growth factor beta) receptor] expression and clinicopathological characteristics, and to evaluate the prognostic significance of TbetaRII expression in breast cancer. METHODS: Clinicopathological data and prognostic information of 108 patients with histologically confirmed breast cancer who were surgically treated at China Medical University between January 2007 and September 2008 were reviewed and the association between the clinicopathological characteristics and TbetaRII expression was analyzed by chi-square test and multivariate analysis. The expression of TbetaRII was assessed by immunohistochemistry. RESULTS: Of the 108 patients, 60 cases were TbetaRII positive and 48 cases were negative. There was no significant association between TbetaRII expression of the patients older than 40 years and that of the younger than 40 years (56.0% vs 50.0%; P = 0.742). The TbetaRII expression rate was significantly increased in patients with lymph node metastasis compared to those without lymph node metastasis (67.40% vs 46.8%; P = 0.033). Statistically significant relationships were found between increasing tumor clinical stage and high TbetaRII expression (P = 0.011). TbetaRII expression was not associated with the expression of ER(estrogen receptor), PR, (progesterone receptor), Her-2 (human epidermal growth factor receptor 2) (P = 0.925,P = 0.861, and P = 0.840, respectively). Patients with high TbetaRII expression showed poorer 5-year disease-free survival (DFS) compared to those with low expression (66.7% vs 45.6%; P = 0.028) by univariate analysis. Survival analysis demonstrated that TbetaRII was associated with poor DFS (P = 0.011). Subgroup analysis revealed that TbetaRII expression was associated with shorter DFS in patients with lymph node metastasis, ER-positive, PR-positive or Her-2-negative tumors (P = 0.006, P = 0.016, P = 0.022, and P = 0.033, respectively). Cox regression analysis revealed that high TbetaRII expression was related to poor 5-year DFS, and it was an independent factor for predicting the poor outcome for breast cancer patients (P = 0.016). CONCLUSIONS: High levels of TbetaRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year DFS in patients with breast cancer. TbetaRII may be a potential prognostic marker for breast cancer. PMID- 26551006 TI - Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality. AB - BACKGROUND: The relationship between central obesity and survival in community dwelling adults with normal body mass index (BMI) is not well-known. OBJECTIVE: To examine total and cardiovascular mortality risks associated with central obesity and normal BMI. DESIGN: Stratified multistage probability design. SETTING: NHANES III (Third National Health and Nutrition Examination Survey). PARTICIPANTS: 15,184 adults (52.3% women) aged 18 to 90 years. MEASUREMENTS: Multivariable Cox proportional hazards models were used to evaluate the relationship of obesity patterns defined by BMI and waist-to-hip ratio (WHR) and total and cardiovascular mortality risk after adjustment for confounding factors. RESULTS: Persons with normal-weight central obesity had the worst long-term survival. For example, a man with a normal BMI (22 kg/m2) and central obesity had greater total mortality risk than one with similar BMI but no central obesity (hazard ratio [HR], 1.87 [95% CI, 1.53 to 2.29]), and this man had twice the mortality risk of participants who were overweight or obese according to BMI only (HR, 2.24 [CI, 1.52 to 3.32] and 2.42 [CI, 1.30 to 4.53], respectively). Women with normal-weight central obesity also had a higher mortality risk than those with similar BMI but no central obesity (HR, 1.48 [CI, 1.35 to 1.62]) and those who were obese according to BMI only (HR, 1.32 [CI, 1.15 to 1.51]). Expected survival estimates were consistently lower for those with central obesity when age and BMI were controlled for. LIMITATIONS: Body fat distribution was assessed based on anthropometric indicators alone. Information on comorbidities was collected by self-report. CONCLUSION: Normal-weight central obesity defined by WHR is associated with higher mortality than BMI-defined obesity, particularly in the absence of central fat distribution. PRIMARY FUNDING SOURCE: National Institutes of Health, American Heart Association, European Regional Development Fund, and Czech Ministry of Health. PMID- 26551007 TI - Erythropoietin Modulates Cerebral and Serum Degradation Products from Excess Calpain Activation following Prenatal Hypoxia-Ischemia. AB - Preterm infants suffer central nervous system (CNS) injury from hypoxia-ischemia and inflammation - termed encephalopathy of prematurity. Mature CNS injury activates caspase and calpain proteases. Erythropoietin (EPO) limits apoptosis mediated by activated caspases, but its role in modulating calpain activation has not yet been investigated extensively following injury to the developing CNS. We hypothesized that excess calpain activation degrades developmentally regulated molecules essential for CNS circuit formation, myelination and axon integrity, including neuronal potassium-chloride co-transporter (KCC2), myelin basic protein (MBP) and phosphorylated neurofilament (pNF), respectively. Further, we predicted that post-injury EPO treatment could mitigate CNS calpain-mediated degradation. Using prenatal transient systemic hypoxia-ischemia (TSHI) in rats to mimic CNS injury from extreme preterm birth, and postnatal EPO treatment with a clinically relevant dosing regimen, we found sustained postnatal excess cortical calpain activation following prenatal TSHI, as shown by the cleavage of alpha II-spectrin (alphaII-spectrin) into 145-kDa alphaII-spectrin degradation products (alphaII SDPs) and p35 into p25. Postnatal expression of the endogenous calpain inhibitor calpastatin was also reduced following prenatal TSHI. Calpain substrate expression following TSHI, including cortical KCC2, MBP and NF, was modulated by postnatal EPO treatment. Calpain activation was reflected in serum levels of alphaII-SDPs and KCC2 fragments, and notably, EPO treatment also modulated KCC2 fragment levels. Together, these data indicate that excess calpain activity contributes to the pathogenesis of encephalopathy of prematurity. Serum biomarkers of calpain activation may detect ongoing cerebral injury and responsiveness to EPO or similar neuroprotective strategies. PMID- 26551009 TI - [Tempora mutantur... et nos? The future of the Hungarian anatomy teaching in reflection of the German trends]. AB - The traditional four-semester anatomy is a subject to change: next to the external pressure, there is an intrinsic need to shift the emphasis. The mapping of the strengths, weaknesses and threats of the Hungarian anatomy teaching helps to formulate the directions of possible development. Current trends in the German medical education should be carefully followed. Nowadays, nearly 25% of the medical students in Germany are studying according to the new, integrated "Modellstudiengang", i.e. all the conventional subjects are reorganised into organ system thematic blocks. The unified German written final exam system provides an objective assessment parameter: to rank the 36 German medical schools according to the results of the anatomy exams. The homepage-published data, the number of semesters or teaching hours, or the thematic concept of the subject alone cannot explain the rankings of the medical schools according to the anatomy exam results. The greatest challenges of the Hungarian anatomy teaching today are: the development of an outcome-oriented, unified, practical system of requirements, the redefinition of the subject, the more effective interaction with the clinical colleagues, solving the problems of faculty recruitment and establishing the vertical integration of anatomy. PMID- 26551008 TI - Novel Etoposide Analogue Modulates Expression of Angiogenesis Associated microRNAs and Regulates Cell Proliferation by Targeting STAT3 in Breast Cancer. AB - Tumor microenvironment play role in angiogenesis and carcinogenesis. Etoposide, a known topoisomerase II inhibitor induces DNA damage resulting in cell cycle arrest. We developed a novel Etoposide analogue, Quinazolino-4beta amidopodophyllotoxin (C-10) that show better efficacy in regulating cell proliferation and angiogenesis. We evaluated its role on expression of microRNAs 15, 16, 17 and 221 and its targets Bcl-2, STAT3 and VEGF that dictate cell proliferation and angiogenesis. Docking studies clearly demonstrated the binding of Etoposide and C-10 to STAT3. We conclude that combination of Etoposide or C-10 with miR-15, 16, 17 and 221 as a new approach to induce apoptosis and control angiogenesis in breast cancer. PMID- 26551010 TI - [How did cholesterol levels change in a village in Bekes County, Hungary, during the last 20 years?]. AB - INTRODUCTION: There are only limited data about the change of cholesterol levels at population level in Hungary. AIM: The aim of the authors was to compare current serum cholesterol levels to those measured 20 years ago in residents of a village in Bekes County, Hungary. METHOD: Using a database of a general ptactitioner, serum cholesterol levels of 778 persons who participated in a screening program in 1994 in the village Mehkerek in Bekes County were compared to those obtained 20 years later from 392 randomly selected persons matching age and gender. RESULTS: The serum total cholesterol level of persons over 50 years was decreased by 5.9%, from 5.94+/-1.41 to 5.59+/-1.33 mmol/L (p<=0.01), while it remained unchanged in persons younger than 50 years of age. CONCLUSIONS: The decrease of serum cholesterol level observed in patients over 50 years of age can be a consequence of the widely used lipid lowering medication. The lack of change in persons below 50 years of age draws the attention that principles of primary prevention (diet, regular physical activity) should be used more consistently, and medical therapy should be applied when it is recommended by the guidelines. PMID- 26551011 TI - [Comparative analysis of attitudes of ambulance personnel and paramedic students regarding death and dying]. AB - INTRODUCTION: The emergency care staff witness the experience of dying and death on a daily basis. AIM: The aim of the study was to evaluate and compare the current and future ambulance personnel's fear of death and its influencing factors. METHOD: Quantitative, cross-sectional comparative study was conducted including 106 participants (active rescue ambulance personnel, n = 45 persons; paramedic students, n = 61). A voluntary, anonymous questionnaire survey method (the Neimeyer-Moore Multidimensional Fear of Death Scale) was used for data collection. The data were analyzed using descriptive and mathematical statistical tests (T-test, analysis of variance). RESULTS: The students had a greater fear in the "Fear for Significant Others" factor (p = 0.001). Students showed stronger fear who lived in cities, had higher educational qualifications, who where women (p = 0.036), singles (p = 0.046), those who have not seen a dying person (p = 0.017) and those who were never witnessed death. Greater fear characterized the ambulance personnel who were village residents, those living in a partnership (p = 0.027), those with lower educational level (p = 0.041) and those who had been working for a longer time. CONCLUSIONS: There is no significant difference between the levels of fear of death of the present and future ambulance personnel. However, the practice-oriented education is very important and, training associated with death and dying should be integrated in the educational schedules of the paramedic students. PMID- 26551012 TI - [Successful treatment of an inoperable periauricular planocellular carcinoma]. AB - Surgery has been considered the first choice of treatment in planocellular skin cancers. However, adjuvant radiotherapy is often required in R1 resection or in lymph node positivity. Inoperable cases are also treated with ionizing radiation with palliative purpose. The authors present a case report of a successful treatment of an 87-year-old diabetic patient with a T4N1M0 stage periauricular destructive tumour treated with 3D conformal adaptive radiotherapy. Complete remission occurred although the initial treatment aim was only palliation. PMID- 26551013 TI - [95 years of the Urology Department of Semmelweis University, Budapest, Hungary]. PMID- 26551015 TI - Balancing research and funding using value of information and portfolio tools for nanomaterial risk classification. AB - Risk research for nanomaterials is currently prioritized by means of expert workshops and other deliberative processes. However, analytical techniques that quantify and compare alternative research investments are increasingly recommended. Here, we apply value of information and portfolio decision analysis methods commonly applied in financial and operations management-to prioritize risk research for multiwalled carbon nanotubes and nanoparticulate silver and titanium dioxide. We modify the widely accepted CB Nanotool hazard evaluation framework, which combines nano- and bulk-material properties into a hazard score, to operate probabilistically with uncertain inputs. Literature is reviewed to develop uncertain estimates for each input parameter, and a Monte Carlo simulation is applied to assess how different research strategies can improve hazard classification. The relative cost of each research experiment is elicited from experts, which enables identification of efficient research portfolios combinations of experiments that lead to the greatest improvement in hazard classification at the lowest cost. Nanoparticle shape, diameter, solubility and surface reactivity were most frequently identified within efficient portfolios in our results. PMID- 26551016 TI - Charge transport in strongly coupled quantum dot solids. AB - The emergence of high-mobility, colloidal semiconductor quantum dot (QD) solids has triggered fundamental studies that map the evolution from carrier hopping through localized quantum-confined states to band-like charge transport in delocalized and hybridized states of strongly coupled QD solids, in analogy with the construction of solids from atoms. Increased coupling in QD solids has led to record-breaking performance in QD devices, such as electronic transistors and circuitry, optoelectronic light-emitting diodes, photovoltaic devices and photodetectors, and thermoelectric devices. Here, we review the advances in synthesis, assembly, ligand treatments and doping that have enabled high-mobility QD solids, as well as the experiments and theory that depict band-like transport in the QD solid state. We also present recent QD devices and discuss future prospects for QD materials and device design. PMID- 26551017 TI - Spin-orbit torque magnetization switching controlled by geometry. AB - Magnetization reversal by an electric current is essential for future magnetic data storage technology, such as magnetic random access memories. Typically, an electric current is injected into a pillar-shaped magnetic element, and switching relies on the transfer of spin momentum from a ferromagnetic reference layer (an approach known as spin-transfer torque). Recently, an alternative technique has emerged that uses spin-orbit torque (SOT) and allows the magnetization to be reversed without a polarizing layer by transferring angular momentum directly from the crystal lattice. With spin-orbit torque, the current is no longer applied perpendicularly, but is in the plane of the magnetic thin film. Therefore, the current flow is no longer restricted to a single direction and can have any orientation within the film plane. Here, we use Kerr microscopy to examine spin-orbit torque-driven domain wall motion in Co/AlOx wires with different shapes and orientations on top of a current-carrying Pt layer. The displacement of the domain walls is found to be highly dependent on the angle between the direction of the current and domain wall motion, and asymmetric and nonlinear with respect to the current polarity. Using these insights, devices are fabricated in which magnetization switching is determined entirely by the geometry of the device. PMID- 26551018 TI - A global analysis of parenchyma tissue fractions in secondary xylem of seed plants. AB - Parenchyma is an important tissue in secondary xylem of seed plants, with functions ranging from storage to defence and with effects on the physical and mechanical properties of wood. Currently, we lack a large-scale quantitative analysis of ray parenchyma (RP) and axial parenchyma (AP) tissue fractions. Here, we use data from the literature on AP and RP fractions to investigate the potential relationships of climate and growth form with total ray and axial parenchyma fractions (RAP). We found a 29-fold variation in RAP fraction, which was more strongly related to temperature than with precipitation. Stem succulents had the highest RAP values (mean +/- SD: 70.2 +/- 22.0%), followed by lianas (50.1 +/- 16.3%), angiosperm trees and shrubs (26.3 +/- 12.4%), and conifers (7.6 +/- 2.6%). Differences in RAP fraction between temperate and tropical angiosperm trees (21.1 +/- 7.9% vs 36.2 +/- 13.4%, respectively) are due to differences in the AP fraction, which is typically three times higher in tropical than in temperate trees, but not in RP fraction. Our results illustrate that both temperature and growth form are important drivers of RAP fractions. These findings should help pave the way to better understand the various functions of RAP in plants. PMID- 26551019 TI - Retrospective comparison of early- versus late-insulin therapy regarding effect on time to resolution of diabetic ketosis and ketoacidosis in dogs and cats: 60 cases (2003-2013). AB - OBJECTIVE: To determine whether early insulin administration (<=6 h after admission) results in more rapid resolution of diabetic ketosis (DK) and ketoacidosis (DKA), shorter duration of hospitalization, and higher incidence of complications, and whether more severe ketonuria is associated with longer time to resolution of DK/DKA. DESIGN: Retrospective study (January 1, 2003-March 1, 2013). SETTING: University teaching hospital. ANIMALS: Sixty dogs and cats with DK or DKA receiving short-acting insulin therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed and data recorded including signalment; previous history of diabetes; intake temperature, blood pressure, blood glucose, pH, base excess, and degree of ketonuria; time to short acting insulin therapy and resolution of DK/DKA; length of hospitalization; and complications. Insulin was initiated <=6 hours in the early group and >6 hours in the late group after hospital admission. Early group patients had more rapid resolution of DK/DKA after starting short-acting insulin therapy (36.4 +/- 22.6 vs. 55.4 +/- 26.6 h, P = 0.014). There was no difference in duration of hospitalization or complications. More severe ketonuria resulted in longer time to resolution of DK/DKA after initiation of short-acting insulin (severe: 50.9 +/ 24.2; moderate: 29.6 +/- 19; mild: 23.4 +/- 21.9 h, P = 0.005, all individual pairwise comparisons P < 0.05). CONCLUSIONS: Early insulin administration is associated with more rapid resolution of DK/DKA without an associated increase in complication rates. DK/DKA took longer to resolve with more severe ketonuria. Prospective studies are warranted to identify specific time targets for insulin administration in DK/DKA patients. PMID- 26551020 TI - Working Toward a Solution: The Unanswered Questions About Silicone Gel Breast Implants. PMID- 26551021 TI - Anti-alpha-enolase is a prognostic marker in postoperative lung cancer patients. AB - Our previous studies suggest that antibodies against ENO1 (anti-ENO1 Ab) have a protective role in patients with non-small cell lung carcinoma. In this study, we evaluated the prognostic value of anti-ENO1 Ab levels in non-small cell lung carcinoma patients undergoing surgery. Circulating levels of anti-ENO1 Ab were assessed in 85 non-small cell lung carcinoma patients before and after surgery, and were correlated with clinical outcome. After surgery, patients with a higher increase of anti-ENO1 Ab had a lower hazard ratio and a better progression-free survival. Using animal models, we demonstrated that tumor cells reduce the circulating levels of anti-ENO1 Ab through physical absorption and neutralization of anti-ENO1 Ab with surface-expressed and secreted ENO1, respectively. Mice transplanted with ENO1-overexpressing tumors generated ENO1-specific regulatory T cells to suppress the production of anti-ENO1 Ab. Our results suggest that the increase of anti-ENO1 Ab may reflect anti-tumor immune responses and serve as a prognostic marker in postoperative lung cancer patients. PMID- 26551022 TI - Global Transcriptome Analysis of the Tentacle of the Jellyfish Cyanea capillata Using Deep Sequencing and Expressed Sequence Tags: Insight into the Toxin- and Degenerative Disease-Related Transcripts. AB - BACKGROUND: Jellyfish contain diverse toxins and other bioactive components. However, large-scale identification of novel toxins and bioactive components from jellyfish has been hampered by the low efficiency of traditional isolation and purification methods. RESULTS: We performed de novo transcriptome sequencing of the tentacle tissue of the jellyfish Cyanea capillata. A total of 51,304,108 reads were obtained and assembled into 50,536 unigenes. Of these, 21,357 unigenes had homologues in public databases, but the remaining unigenes had no significant matches due to the limited sequence information available and species-specific novel sequences. Functional annotation of the unigenes also revealed general gene expression profile characteristics in the tentacle of C. capillata. A primary goal of this study was to identify putative toxin transcripts. As expected, we screened many transcripts encoding proteins similar to several well-known toxin families including phospholipases, metalloproteases, serine proteases and serine protease inhibitors. In addition, some transcripts also resembled molecules with potential toxic activities, including cnidarian CfTX-like toxins with hemolytic activity, plancitoxin-1, venom toxin-like peptide-6, histamine-releasing factor, neprilysin, dipeptidyl peptidase 4, vascular endothelial growth factor A, angiotensin-converting enzyme-like and endothelin-converting enzyme 1-like proteins. Most of these molecules have not been previously reported in jellyfish. Interestingly, we also characterized a number of transcripts with similarities to proteins relevant to several degenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases. This is the first description of degenerative disease-associated genes in jellyfish. CONCLUSION: We obtained a well-categorized and annotated transcriptome of C. capillata tentacle that will be an important and valuable resource for further understanding of jellyfish at the molecular level and information on the underlying molecular mechanisms of jellyfish stinging. The findings of this study may also be used in comparative studies of gene expression profiling among different jellyfish species. PMID- 26551024 TI - Bringing Leukemia Stem Cells into the Clinic. AB - Outcomes in acute myeloid leukemia (AML) remain poor due to high rates of relapse. Thus, there is an urgent unmet medical need for new therapies that can more effectively kill the leukemia stem cells (LSC) and recently recognized preleukemic hematopoietic stem cells (preL-HSC) that can drive relapsed disease. In order to develop such therapies, a better understanding of the biology of these stem cell populations is required. The best functional assays for stem cells are xenotransplantation models using immunodeficient mouse recipients. Here, we present evidence of the clinical validity of such models for studying the biology of AML stem cells and propose a new paradigm for the development of LSC-targeted agents and biomarker tools for patient selection. PMID- 26551025 TI - Tau as the Converging Protein between Chronic Stress and Alzheimer's Disease Synaptic Pathology. AB - BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology and still undefined initiators. Several risk factors have been suggested for AD with recent evidence supporting an etiopathogenic role of chronic environmental stress and glucocorticoids (GCs, stress hormones) in the development of the disease. Indeed, both AD and chronic stress are associated with neuronal atrophy, synaptic loss and cognitive impairment. Our previous studies have demonstrated the aggravating role of stress and GCs on AD pathology, including Tau hyperphosphorylation and aggregation and cognitive deficits in various AD models. In light of the suggested involvement of Tau missorting in AD synaptotoxity and the dual cytoplasmic and synaptic role of Tau, our recent studies focused on the possible role of Tau in the underlying cascades of stress/GC neuronal malfunction/atrophy in wild-type animals by monitoring the intracellular localization of Tau and its phosphorylation status in different cellular compartments. SUMMARY: Biochemical, ultrastructural, behavioral and neurostructural analysis have helped demonstrate that prolonged GC administration leads to dendritic remodeling and spine atrophy and loss in the rat hippocampus triggering Tau missorting at hippocampal synapses with the participation of specific phosphorylated Tau isoforms in this synaptic accumulation. KEY MESSAGES: The above findings suggest that Tau plays an essential role in mediating the neurodegenerative effects of stress and GCs towards the development of AD pathology. In addition, they highlight the involvement of Tau missorting in mechanism(s) of synaptic atrophy, beyond AD adding to our limited knowledge of the mechanisms through which stress causes brain pathology. PMID- 26551023 TI - Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials. AB - BACKGROUND: Infection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB. OBJECTIVE: Systematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR). SEARCH STRATEGY: Electronic databases were searched to identify relevant articles in English available by September 11th 2015. SELECTION CRITERIA: Research articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials. DATA ANALYSIS: A qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity. MAIN RESULTS: This review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis. CONCLUSIONS: IPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals. PMID- 26551026 TI - Sensory Characteristics and Comparison of Commercial Plain Yogurts and 2 New Production Sample Options. AB - This research determined the sensory characteristics of currently available plain yogurts available in U.S. supermarkets and examined how 3 "more sustainable" prototypes compared. The prototypes, nonfat set-style yogurts pre-acidified after pasteurization with lemon juice or citric acid at 80 ppm to pH 6.2, had shorter fermentation times than the lab-made control. These reduced fermentation times could result in energy reductions and potentially substantiate a "sustainable" marketing claim, a concept gaining traction with consumers. Twenty-six commercial yogurts, varying in percent milk fat, milk source (organic or conventional), and processing (set-style, stirred, or strained/Greek-style), were also included. Using descriptive sensory analysis, a 6-person highly trained panel scored the intensity of 25 flavor and 10 texture attributes on a 15-point scale. Three replications were carried out, and all samples were tested at least 10 d prior to the end of their shelf-lives. The samples differed for 19 flavor and all 10 texture attributes. Cluster analysis indicated approximately 7 flavor and 5 texture clusters. The prototype pre-acidified with lemon juice was similar to category leaders nonfat yogurt varieties. The prototype pre-acidified with citric acid was similar in texture but was less sour. Although no legal definitions exist for "sustainable," the prototypes' sensory characteristics are comparable to those of popular yogurts indicating potential market viability. This research also demonstrates potential for making yogurt that is in line with growing consumer expectations for sustainability. Despite the current diversity, several combinations of flavor and texture were not represented. PMID- 26551027 TI - Lead exposure reduces carotenoid-based coloration and constitutive immunity in wild mallards. AB - The ingestion of spent lead (Pb) from ammunition is a known cause of mortality in waterfowl, but little is known about sublethal effects produced by Pb poisoning on birds, especially in wild populations. The authors studied potential sublethal effects associated with Pb exposure in mallards (Anas platyrhynchos) from the Ebro delta (northeastern Spain) after a ban on Pb ammunition. They analyzed the relationships between blood Pb levels and oxidative stress, immune response, and carotenoid-based coloration, which are known to be influenced by oxidative stress. Levels of Pb were reduced by half from 6 yr to 9 yr after the ban. Lipid peroxidation was positively related to Pb levels in females. The delta aminolevulinic acid dehydratase activity was suppressed by Pb exposure and negatively associated with the activity of antioxidant enzymes. Carotenoid levels were positively associated with blood Pb concentration in both sexes, and males with higher Pb levels presented a less intense coloration in legs and beak. Levels of Pb were positively related to hemolytic activity of circulating immune system components and negatively related to lysozyme levels. In summary, Pb exposure was associated in a gender-specific way with increased oxidative stress, consequences on color expression, and impaired constitutive immunity. In females, antioxidants seemed to be allocated mostly in reproduction rather than in self maintenance, whereas males seemed to better maintain oxidative balance to the detriment of coloration. Environ Toxicol Chem 2016;35:1516-1525. (c) 2015 SETAC. PMID- 26551028 TI - Comparison of high-dose intravenous immunoglobulin (IVIG) in a 5% and a 10% solution does not reveal a significantly different spectrum of side-effects. PMID- 26551029 TI - Phosphorylcholine-Based Zwitterionic Biocompatible Thermogel. AB - Zwitterionic polymers have been investigated as surface-coating materials due to their low protein adsorption properties, which reduce immunogenicity, biofouling, and bacterial adsorption of coated materials. Most zwitterionic polymers, reported so far, are based on (meth)acrylate polymers which can induce toxicity by residual monomers or amines produced by degradation. Here, we report a new zwitterionic polymer consisting of phosphorylcholine (PC) and biocompatible poly(propylene glycol) (PPG) as a new thermogelling material. The PC-PPG-PC polymer aqueous solution undergoes unique multiple sol-gel transitions as the temperature increases. A heat-induced unimer-to-micelle transition, changes in ionic interactions, and dehydration of PPG are involved in the sol-gel transitions. Based on the broad gel window and low protein adsorption properties, the PC-PPG-PC thermogel is proved for sustained delivery of protein drugs and stem cells over 1 week. PMID- 26551030 TI - Flexibility is Key: Synthesis of a Tripyridylamine (TPA) Congener with a Phosphorus Apical Donor and Coordination to Cobalt(II). AB - Tripyridylamine (TPA), a tetradentate ligand that forms 5-membered chelate rings upon metal coordination, has demonstrated significant utility in synthetic inorganic chemistry. An analogue with a phosphorus apical donor is a desirable target for tuning electronic structure and enhancing reactivity. However, this congener has been synthetically elusive. Prior attempts have resulted in tridentate coordination to transition metal ions due to a lack of ligand flexibility. Herein, we report the successful synthesis of tris(2 pyridylmethyl)proazaphosphatrane (TPAP), a more accommodating tripyridyl ligand containing an apical phosphorus donor. The TPAP ligand forms 6-membered chelate rings upon coordination and binds in the desired tetradentate fashion to a Co(II) ion. Structural studies elucidate the importance of ligand flexibility in tripodal ligands featuring phosphorus donors. Cyclic voltammetry, UV-vis, and solution magnetic susceptibility experiments of [Co(TPAP)(CH3CN)](2+) are also reported and compared to [Co(TPA)(CH3CN)](2+). Notably, magnetic susceptibility measurements of [Co(TPAP)(CH3CN)](2+) indicate a low spin electronic configuration, in contrast to [Co(TPA)(CH3CN)](2+), which is high spin. PMID- 26551031 TI - Treatment of Renal Stones >=20 mm with Extracorporeal Shock Wave Lithotripsy. AB - AIMS: To identify subgroups of patients with renal stones >=20 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy. METHODS: A total of 376 patients with renal stones >=20 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious. RESULTS: At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area <=50% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones <=400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film. CONCLUSIONS: For renal stones with a surface area <=400 mm2 and a radiodensity equal to or less than that of the 12th rib as determined by a KUB film, ESWL may be considered the first line of treatment, even for stones with a diameter >=20 mm. For large stones requiring repeat treatments, the surface area of the residual stones after the first ESWL is a predictor of the final treatment result. PMID- 26551032 TI - Large Variability of Proanthocyanidin Content and Composition in Sainfoin (Onobrychis viciifolia). AB - Proanthocyanidins (PAs) in sainfoin (Onobrychis viciifolia Scop.) are of interest to ameliorate the sustainability of livestock production. However, sainfoin forage yield and PA concentrations, as well as their composition, require optimization. Individual plants of 27 sainfoin accessions from four continents were analyzed with LC-ESI-QqQ-MS/MS for PA concentrations and simple phenolic compounds. Large variability existed in PA concentrations (23.0-47.5 mg g(-1) leaf dry matter (DM)), share of prodelphinidins (79-96%), and mean degree of polymerization (11-14) among, but also within, accessions. PAs were mainly located in leaves (26.8 mg g(-1) DM), whereas stems had less PAs (7.8 mg g(-1) DM). Overall, high-yielding plants had lower PA leaf concentrations (R(2) = 0.16, P < 0.001) and fewer leaves (R(2) = 0.66, P < 0.001). However, the results show that these two trade-offs between yield and bioactive PAs can be overcome. PMID- 26551033 TI - Cross-dressing: an alternative mechanism for antigen presentation. AB - Cross-dressing involves the transfer of preformed functional peptide-MHC complexes from the surface of donor cells to recipient cells, such as dendritic cells (DCs). These cross-dressed cells might eventually present the intact, unprocessed peptide-MHC complexes to T lymphocytes. In this review we will discuss some recent findings concerning the intercellular transfer of preformed MHC complexes and the possible mechanisms by which the transfer may occur. We will report evidences showing that both MHC class I and MHC class II functional complexes might be transferred, highlighting the physiological relevance of these cross-dressed cells for the presentation of exogenous antigens to both cytotoxic and helper T lymphocytes. PMID- 26551034 TI - Discovery and Structure-Guided Optimization of Diarylmethanesulfonamide Disrupters of Glucokinase-Glucokinase Regulatory Protein (GK-GKRP) Binding: Strategic Use of a N -> S (nN -> sigma*S-X) Interaction for Conformational Constraint. AB - The HTS-based discovery and structure-guided optimization of a novel series of GKRP-selective GK-GKRP disrupters are revealed. Diarylmethanesulfonamide hit 6 (hGK-hGKRP IC50 = 1.2 MUM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 MUM). A stabilizing interaction between a nitrogen atom lone pair and an aromatic sulfur system (nN -> sigma*S-X) in 32 was exploited to conformationally constrain a biaryl linkage and allow contact with key residues in GKRP. Lead compound 32 was shown to induce GK translocation from the nucleus to the cytoplasm in rats (IHC score = 0; 10 mg/kg po, 6 h) and blood glucose reduction in mice (POC = -45%; 100 mg/kg po, 3 h). X-ray analyses of 32 and several precursors bound to GKRP were also obtained. This novel disrupter of GK GKRP binding enables further exploration of GKRP as a potential therapeutic target for type II diabetes and highlights the value of exploiting unconventional nonbonded interactions in drug design. PMID- 26551035 TI - Assessing the Quality of Sick Child Care Provided by Community Health Workers. AB - BACKGROUND: As community case management of childhood illness expands in low income countries, there is a need to assess the quality of care provided by community health workers. This study had the following objectives: 1) examine methods of recruitment of sick children for assessment of quality of care, 2) assess the validity of register review (RR) and direct observation only (DO) compared to direct observation with re-examination (DO+RE), and 3) assess the effect of observation on community health worker performance. METHODS: We conducted a survey to assess the quality of care provided by Ethiopian Health Extension Workers (HEWs). The sample of children was obtained through spontaneous consultation, HEW mobilization, or recruitment by the survey team. We assessed patient characteristics by recruitment method. Estimates of indicators of quality of care obtained using RR and DO were compared to gold standard estimates obtained through DO+RE. Sensitivity, specificity, and the area under receiver operator characteristic curve (AUC) were calculated to assess the validity of RR and DO. To assess the Hawthorne effect, we compared estimates from RR for children who were observed by the survey team to estimates from RR for children who were not observed by the survey team. RESULTS: Participants included 137 HEWs and 257 sick children in 103 health posts, plus 544 children from patient registers. Children mobilized by HEWs had the highest proportion of severe illness (27%). Indicators of quality of care from RR and DO had high sensitivity for most indicators, but specificity was low. The AUC for different indicators from RR ranged from 0.47 to 0.76, with only one indicator above 0.75. The AUC of indicators from DO ranged from 0.54 to 1.0, with three indicators above 0.75. The differences between estimates of correct care for observed versus not observed children were small. CONCLUSIONS: Mobilization by HEWs and recruitment by the survey teams were feasible, but potentially biased, methods of obtaining sick children. Register review and DO underestimated performance errors. Our data suggest that being observed had only a small positive effect on the performance of HEWs. PMID- 26551036 TI - Comparison of Recombination Dynamics in CH3NH3PbBr3 and CH3NH3PbI3 Perovskite Films: Influence of Exciton Binding Energy. AB - Understanding carrier recombination in semiconductors is a critical component when developing practical applications. Here we measure and compare the monomolecular, bimolecular, and trimolecular (Auger) recombination rate constants of CH3NH3PbBr3 and CH3NH3PbI3. The monomolecular and bimolecular recombination rate constants for both samples are limited by trap-assisted recombination. The bimolecular recombination rate constant for CH3NH3PbBr3 is ~3.3 times larger than that for CH3NH3PbI3 and both are in line with that found for radiative recombination in other direct-gap semiconductors. The Auger recombination rate constant is 4 times larger in lead-bromide-based perovskite compared with lead iodide-based perovskite and does not follow the reduced Auger rate when the bandgap increases. The increased Auger recombination rate, which is enhanced by Coulomb interactions, can be ascribed to the larger exciton binding energy, ~40 meV, in CH3NH3PbBr3 compared with ~13 meV in CH3NH3PbI3. PMID- 26551038 TI - The Radical Anion of Cyclopentasilane-Fused Hexasilabenzvalene. AB - The radical anion of cyclopentasilane-fused hexasilabenzvalene was synthesized by the reduction of the corresponding neutral compound. X-ray crystallographic analysis showed a more trans-bent structure of the disilene moiety than the neutral compound. Theoretical calculations showed that the highly trans-bent structure is attributed to the hexasilabenzvalene structure. The EPR spectrum showed that an unpaired electron exists mainly at the disilene moiety. In the UV/Vis spectrum, a large bathochromic shift was observed compared with the neutral compound. PMID- 26551039 TI - Relative Photoionization Cross Sections of Super-Atom Molecular Orbitals (SAMOs) in C60. AB - The electronic structure and photoinduced dynamics of fullerenes, especially C60, is of great interest because these molecules are model systems for more complex molecules and nanomaterials. In this work we have used Rydberg Fingerprint Spectroscopy to determine the relative ionization intensities from excited SAMO (Rydberg-like) states in C60 as a function of laser wavelength. The relative ionization intensities are then compared to the ratio of the photoionization widths of the Rydberg-like states, computed in time-dependent density functional theory (TD-DFT). The agreement is remarkably good when the same photon order is required to energetically access the excited states. This illustrates the predictive potential of quantum chemistry for studying photoionization of large, complex molecules as well as confirming the assumption that is often made concerning the multiphoton excitation and rapid energy redistribution in the fullerenes. PMID- 26551037 TI - Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains. AB - Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL. PMID- 26551040 TI - Emergency Laparoscopic Sigmoidectomy for Perforated Diverticulitis with Generalised Peritonitis: A Systematic Review. AB - BACKGROUND: Laparoscopic sigmoidectomy for diverticulitis has initially been confined to the elective setting. However, open acute sigmoidectomy for perforated diverticulitis is associated with high morbidity rates that might be reduced after laparoscopic surgery. The aim of this systematic review was to assess the feasibility of emergency laparoscopic sigmoidectomy for perforated diverticulitis. METHODS: We performed a systematic search of PubMed, EMBASE and CENTRAL. All studies reporting on patients with perforated diverticulitis (Hinchey III-IV) treated by laparoscopic sigmoidectomy in the acute phase were included, regardless of design. RESULTS: We included 4 case series and one cohort study (total of 104 patients) out of 1,706 references. Hartmann's procedure (HP) was performed in 84 patients and primary anastomosis in 20. The mean operating time varied between 115 and 200 min. The conversion rate varied from 0 to 19%. The mean length of hospital stay ranged between 6 and 16 days. Surgical re intervention was necessary in 2 patients. In 20 patients operated upon without defunctioning ileostomy, no anastomotic leakage was reported. Three patients died during the postoperative period. Stoma reversal after HP was performed in 60 out of 79 evaluable patients (76%). CONCLUSIONS: Acute laparoscopic sigmoidectomy for the treatment of perforated diverticulitis is feasible in selected patients provided they are handled by experienced hands. PMID- 26551041 TI - Energy and Electron Transfer Dynamics within a Series of Perylene Diimide/Cyclophane Systems. AB - Artificial photosynthetic systems for solar energy conversion exploit both covalent and supramolecular chemistry to produce favorable arrangements of light harvesting and redox-active chromophores in space. An understanding of the interplay between key processes for photosynthesis, namely light-harvesting, energy transfer, and photoinduced charge separation and the design of novel, self assembling components capable of these processes are imperative for the realization of multifunctional integrated systems. We report our investigations on the potential of extended tetracationic cyclophane/perylene diimide systems as components for artificial photosynthetic applications. We show how the selection of appropriate heterocycles, as extending units, allows for tuning of the electron accumulation and photophysical properties of the extended tetracationic cyclophanes. Spectroscopic techniques confirm energy transfer between the extended tetracationic cyclophanes and perylene diimide is ultrafast and quantitative, while the heterocycle specifically influences the energy transfer related parameters and the acceptor excited state. PMID- 26551042 TI - The twofold diagnosis of personality disorder: How do personality dysfunction and pathological traits increment each other at successive levels of the trait hierarchy? AB - Besides the categorical classification of personality disorders (PDs) in Section II of the DSM-5 (American Psychiatric Association, 2013), which has been transferred as such from DSM-IV, Section III provides an alternative model to stimulate further research on the dimensional conceptualization of PDs. In this alternative system, a PD diagnosis is based on 2 essential criteria: impaired personality functioning and the presence of pathological traits. One topic that warrants further research concerns the incremental validity of these 2 components. The current study addresses this issue in a mixed community-patient sample (N = 233). First, Goldberg's (2006) "bass-ackwards" method was used to examine the hierarchical structure of pathological traits as measured by the Dimensional Assessment of Personality Pathology (DAPP-BQ; Livesley & Jackson, 2009). We then extracted a single higher order factor from the Severity Index of Personality Problems (SIPP-118; Verheul et al., 2008) to derive 1 coherent indicator of personality dysfunction. Correlation and hierarchical regression analyses were used to determine the incremental validity of the dysfunction factor versus the trait components at succeeding levels of the DAPP-BQ hierarchy. The results only partially supported the 2-component PD diagnosis, as traits and dysfunction appeared to have only limited incremental validity. Moreover, lower order traits were generally unable to outperform higher order components in predicting specific DSM-IV PDs. Implications for the conceptualization and assessment of personality pathology are discussed. (PsycINFO Database Record PMID- 26551043 TI - Daily diary study of personality disorder traits: Momentary affect and cognitive appraisals in response to stressful events. AB - Difficulties in emotional expression and emotion regulation are core features of many personality disorders (PDs); yet, we know relatively little about how individuals with PDs affectively respond to stressful situations. The present study seeks to fill this gap in the literature by examining how PD traits are associated with emotional responses to subjective daily stressors, while accounting for cognition and type of stressor experienced (interpersonal vs. noninterpersonal). PD features were measured with the Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2) diagnostic scores. Participants (N = 77) completed a 1-week experience sampling procedure that measured affect and cognition related to a current stressor 5 times per day. Hierarchical linear modeling (HLM) was used to examine whether and how baseline PD features, momentary cognitions, and type of stressor predicted level of affect. Results demonstrated that paranoid, borderline, and avoidant PD traits predicted negative affect beyond what could be accounted for by cognitions and type of stressor. No PD traits predicted positive affect after accounting for the effects of cognitive appraisals and type of stressor. Findings have implications for validating the role of affect in PDs and understanding how individuals with PDs react in the presence of daily hassles. (PsycINFO Database Record PMID- 26551044 TI - Er:YAG ablative fractional laser-primed photodynamic therapy with methyl aminolevulinate as an alternative treatment option for patients with thin nodular basal cell carcinoma: 12-month follow-up results of a randomized, prospective, comparative trial. AB - BACKGROUND: Surgical excision is conventionally regarded as the treatment of choice for nodular basal cell carcinoma (nBCC), and methyl aminolevulinate photodynamic therapy (MAL-PDT) has relatively low efficacy for nBCC. However, Er:YAG ablative fractional laser (AFL)-primed MAL-PDT (Er:YAG AFL-PDT) may offer enhanced efficacy for nBCC, especially thin nBCC (thickness <=2 mm). OBJECTIVE: We compared Er:YAG AFL-PDT with conventional MAL-PDT for thin facial nBCC in Korean patients. METHODS: Thirty-nine patients (42 lesions) with primary, histologically proven thin nBCCs were randomized to Er:YAG AFL-PDT (single session, n = 20) or conventional MAL-PDT (two sessions, 7 days apart, n = 19). Efficacy, recurrence rate, cosmetic outcomes and safety were assessed 1 week, 3 months and 12 months after the last treatment. RESULTS: Three months after the final treatment, overall complete response rates were 84.2% with Er:YAG AFL-PDT and 50% with MAL-PDT (P = 0.026). The recurrence rate was significantly lower with Er:YAG AFL-PDT (6.3%) than with MAL-PDT (55.6%) at 12 months (P = 0.006). Er:YAG AFL-PDT and MAL-PDT did not differ significantly with respect to cosmetic outcomes or safety. CONCLUSIONS: Er:YAG AFL-PDT can be used as an alternative treatment option for patients who have thin nBCC and are not suitable for surgical treatment. PMID- 26551045 TI - Glucagon-Like Peptide-1 Formulation--the Present and Future Development in Diabetes Treatment. AB - Type 2 diabetes mellitus is a chronic metabolic disorder that has become the fourth leading cause of death in the developed countries. The disorder is characterized by pancreatic beta-cells dysfunction, which causes hyperglycaemia leading to several other complications. Treatment by far, which focuses on insulin administration and glycaemic control, has not been satisfactory. Glucagon like peptide-1 (GLP1) is an endogenous peptide that stimulates post-prandial insulin secretion. Despite being able to mimic the effect of insulin, GLP1 has not been the target drug in diabetes treatment due to the peptide's metabolic instability. After a decade-long effort to improve the pharmacokinetics of GLP1, a number of GLP1 analogues are currently available on the market. The current Minireview does not discuss these drugs but presents strategies that were undertaken to address the weaknesses of the native GLP1, particularly drug delivery techniques used in developing GLP1 nanoparticles and modified GLP1 molecule. The article highlights how each of the selected preparations has improved the efficacy of GLP1, and more importantly, through an overview of these studies, it will provide an insight into strategies that may be adopted in the future in the development of a more effective oral GLP1 formulation. PMID- 26551046 TI - Luminescent Polymer Composite Films Containing Coal-Derived Graphene Quantum Dots. AB - Luminescent polymer composite materials, based on poly(vinyl alcohol) (PVA), as a matrix polymer and graphene quantum dots (GQDs) derived from coal, were prepared by casting from aqueous solutions. The coal-derived GQDs impart fluorescent properties to the polymer matrix, and the fabricated composite films exhibit solid state fluorescence. Optical, thermal, and fluorescent properties of the PVA/GQD nanocomposites have been studied. High optical transparency of the composite films (78 to 91%) and excellent dispersion of the nanoparticles are observed at GQD concentrations from 1 to 5 wt %. The maximum intensity of materials photoluminescence has been achieved at 10 wt % GQD content. These materials could be used in light emitting diodes (LEDs), flexible electronic displays, and other optoelectronic applications. PMID- 26551047 TI - Diabetes Screening Among Underserved Adults With Severe Mental Illness Who Take Antipsychotic Medications. PMID- 26551049 TI - Comparative tissue expression of American lobster (Homarus americanus) immune genes during bacterial and scuticociliate challenge. AB - The American lobster (Homarus americanus) fishery is the most economically significant fishery in Canada; although comparatively little is known about the lobsters' response to pathogenic challenge. This is the first study to investigate the expression of immune genes in tissues outside of the lobster hepatopancreas in response to challenges by the Gram-positive bacteria, Aerococcus viridans var. homari or the scuticociliate parasite, Anophryoides haemophila. The hepatopancreas has been regarded as the major humoral immune organ in crustaceans, but the contribution of other organs and tissues to the molecular immune response has largely been overlooked. This study used RT-qPCR to monitor the gene expression of several immune genes including three anti lipopolysaccharide isoforms (ALF) Homame ALF-B1, Homame ALF-C1 and ALFHa-1, acute phase serum amyloid protein A (SAA), as well as thioredoxin and hexokinase, in antennal gland and gill tissues. Our findings indicate that the gene expression of the SAA and all ALF isoforms in the antennal gland and gill tissues increased in response to pathogenic challenge. However, there was differential expression of individual ALF isoforms that were dependent on both the tissue, and the pathogen used in the challenge. The gene expression changes of several immune genes were found to be higher in the antennal gland than have been previously reported for the hepatopancreas. This study demonstrates that increased immune gene expression from the gill and antennal gland over the course of pathogen induced disease contributes to the immune response of H. americanus. PMID- 26551050 TI - Identification and characterization of a novel Toll-like receptor 2 homologue in the large yellow croaker Larimichthys crocea. AB - Toll-like receptors (TLRs) are key components of innate immunity that play significant roles in immune defence against pathogen invasion. In the present study, we identified a novel TLR2 homologue (LycTLR2b) in large yellow croaker (Larimichthys crocea) that shared low sequence identity with the previously reported large yellow croaker TLR2 (tentatively named LycTLR2a). The full-length cDNA of LycTLR2b was 2926 nucleotides (nt) long and encoded a protein consisting of 797 amino acids (aa). The deduced LycTLR2b protein exhibited a typical TLR domain architecture including a signal peptide, seven leucine-rich repeats (LRRs) in the extracellular region, a transmembrane domain, and a Toll-Interleukin 1 receptor (TIR) domain in the cytoplasmic region. Phylogenetic analysis showed that both LycTLR2a and LycTLR2b fall into a major clade formed by all TLR2 sequences, and are divided into two distinct branches. Genomic organization revealed that the LycTLR2b gene lacks intron, which is similar to zebrafish and human TLR2 genes, whereas the LycTLR2a gene contains multiple introns, as found in damselfish TLR2a and Fugu TLR2 genes. Syntenic analysis suggested that the occurrence of LycTLR2a and LycTLR2b may result from a relatively recent genome duplication event. LycTLR2b mRNA was constitutively expressed in all tissues examined although at different levels. Following bacterial vaccine challenge, LycTLR2b expression levels were significantly up-regulated in both spleen and head kidney tissues. Taken together, these results indicated that two different TLR2 homologues, which may play roles in antibacterial immunity, exist in large yellow croaker. PMID- 26551052 TI - Systematic review of cardiopulmonary exercise testing post stroke: Are we adhering to practice recommendations? AB - OBJECTIVE: To systematically review the use of cardiopulmonary exercise testing in people who have survived a stroke. The following questions are addressed: (i) What are the testing procedures used? (ii) What are the patient, safety and outcomes characteristics in the cardiopulmonary exercise testing procedures? (iii) Which criteria are used to determine maximum oxygen uptake (VO2peak/max) in the cardiopulmonary exercise testing procedures? METHODS: Systematic review of studies of cardiopulmonary exercise testing in stroke survivors. PubMed, EMBASE, and CINAHL were searched from inception until January 2014. MeSH headings and keywords used were: oxygen capacity, oxygen consumption, oxygen uptake, peak VO2, max VO2, aerobic fitness, physical fitness, aerobic capacity, physical endurance and stroke. Search and selection were performed independently by 2 reviewers. Sixty studies were scrutinized, including 2,104 stroke survivors. RESULTS: Protocols included treadmill (n = 21), bicycle (n = 33), stepper (n = 3) and arm (n = 1) ergometry. Five studies reported 11 adverse events (1%). Secondary outcomes were reported in few studies, which hampered interpretation of the patient's effort, and hence the value of the VO2peak. CONCLUSION: Most studies did not adhere, or insufficiently adhered, to the existing cardiopulmonary exercise testing guidelines for exercise testing. Thus, the results of cardiopulmonary exercise testing protocols in stroke patients cannot be compared. PMID- 26551051 TI - Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. AB - BACKGROUND: Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. OBJECTIVE: To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). SETTING: 48 U.S. sites. PATIENTS: 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. MEASUREMENTS: Sustained virologic response at 12 weeks (SVR12). RESULTS: In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. LIMITATION: The study was open-label, no inferential statistics were planned, and sample sizes were small. CONCLUSION: Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. PRIMARY FUNDING SOURCE: Gilead Sciences. PMID- 26551053 TI - Wittig Reaction: Domino Olefination and Stereoselectivity DFT Study. Synthesis of the Miharamycins' Bicyclic Sugar Moiety. AB - 2-O-Acyl protected-d-ribo-3-uloses reacted with [(ethoxycarbonyl)methylene]triphenylphosphorane in acetonitrile to afford regio- and stereoselectively 2-(Z)-alkenes in 10-60 min under microwave irradiation. This domino reaction is proposed to proceed via tautomerization of 3-ulose to enol, acyl migration, tautomerization to the 3-O-acyl-2-ulose, and Wittig reaction. Alternatively, in chloroform, regioselective 3-olefination of 2-O pivaloyl-3-uloses gave (E)-alkenes, key precursors for the miharamycins' bicyclic sugar moiety. PMID- 26551055 TI - A Bioinspired Multifunctional Heterogeneous Membrane with Ultrahigh Ionic Rectification and Highly Efficient Selective Ionic Gating. AB - A bioinspired multifunctional heterogeneous membrane composed of a block copolymer (PS-b-P4VP) membrane and a porous anodic alumina membrane is fabricated. The ionic rectification is so strong that the maximum ratio is ~489, and the chemical actuation of the anion or cation gate from the "OFF" to the "ON" state promotes a 98.5% increase in the channel conductance. PMID- 26551054 TI - Select Rab GTPases Regulate the Pulmonary Endothelium via Endosomal Trafficking of Vascular Endothelial-Cadherin. AB - Pulmonary edema occurs in settings of acute lung injury, in diseases, such as pneumonia, and in acute respiratory distress syndrome. The lung interendothelial junctions are maintained in part by vascular endothelial (VE)-cadherin, an adherens junction protein, and its surface expression is regulated by endocytic trafficking. The Rab family of small GTPases are regulators of endocytic trafficking. The key trafficking pathways are regulated by Rab4, -7, and -9. Rab4 regulates the recycling of endosomes to the cell surface through a rapid-shuttle process, whereas Rab7 and -9 regulate trafficking to the late endosome/lysosome for degradation or from the trans-Golgi network to the late endosome, respectively. We recently demonstrated a role for the endosomal adaptor protein, p18, in regulation of the pulmonary endothelium through enhanced recycling of VE cadherin to adherens junction. Thus, we hypothesized that Rab4, -7, and -9 regulate pulmonary endothelial barrier function through modulating trafficking of VE-cadherin-positive endosomes. We used Rab mutants with varying activities and associations to the endosome to study endothelial barrier function in vitro and in vivo. Our study demonstrates a key role for Rab4 activation and Rab9 inhibition in regulation of vascular permeability through enhanced VE-cadherin expression at the interendothelial junction. We further showed that endothelial barrier function mediated through Rab4 is dependent on extracellular signal regulated kinase phosphorylation and activity. Thus, we demonstrate that Rab4 and -9 regulate VE-cadherin levels at the cell surface to modulate the pulmonary endothelium through extracellular signal-regulated kinase-dependent and independent pathways, respectively. We propose that regulating select Rab GTPases represents novel therapeutic strategies for patients suffering with acute respiratory distress syndrome. PMID- 26551057 TI - A frustrated ferrimagnet Cu5(VO4)2(OH)4 with a 1/5 magnetization plateau on a new spin-lattice of alternating triangular and honeycomb strips. AB - Cu5(VO4)2(OH)4 (turanite) is a layered compound, exhibiting a copper(II) oxide layer in the [0 1 1] plane composed of edge-sharing CuO6 octahedra. Each Cu-O layer is further separated by VO4 tetrahedra. Closer scrutiny found that the copper(II) oxide layer in the compound represents a totally new geometrically frustrated lattice, a 1/6 depleted triangular lattice. More specifically, the spin network in the [0 1 1] plane is formed by the alternate ranking of triangular and honeycomb strips. Magnetic measurements show that the Cu5(VO4)2(OH)4 behaves as a spin-1/2 ferrimagnet with a Tc = ~4.5 K. It exhibits an unusual 1/5 magnetization plateau arising from the competition between antiferromagnetic and ferromagnetic interactions caused by the strong frustration. The possible spin-arrangements are also suggested. PMID- 26551056 TI - Ecophysiology of environmental Aspergillus fumigatus and comparison with clinical strains on gliotoxin production and elastase activity. AB - The aim of this manuscript was to study the influence of water activity (aW ) and pH in the ecophysiological behaviour of Aspergillus fumigatus strains at human body temperature. In addition, gliotoxin production and enzymatic ability among environmental (n = 2) and clinical (n = 5) strains were compared. Ecophysiological study of environmental strains was performed on agar silage incubated at 37 degrees C, studying the interaction at eight aW levels (0.8, 0.85, 0.9, 0.92, 0.94, 0.96, 0.98 and 0.99) and eight pH levels (3.5, 4, 4.5, 5, 6, 7, 7.5 and 8). Considering the influence of the assumed lung conditions on growth of A. fumigatus (aW 0.98/0.99 and pH of 7/7.5), the optimal condition for the development of A. fumigatus RC031 was at aW 0.99 at pH 7. At aW 0.98/0.99 and pH of 7/7.5, the highest growth rate and the lowest lag phase was reported, whereas there were no significant differences at aW 0.98/0.99 and pH 7/7.5 interactions on growth of A. fumigatus RC032. Gliotoxin production of A. fumigatus strains was evaluated. The gliotoxin production was similar in clinical and environmental strains. Elastin activity was studied in solid medium, highest elastase activity index was found for clinical strain A. fumigatus RC0676, followed by the environmental strain A. fumigatus RC031. Opportunistic environmental strains can be considered as pathogenic in some cases when rural workers are exposed constantly to handling silage. SIGNIFICANCE AND IMPACT OF THE STUDY: Aspergillus fumigatus is one of the main opportunist pathogen agents causing invasive aspergillosis. Rural workers present a constant exposition to A. fumigatus spores caused by feed-borne manipulation. In this study, environmental A. fumigatus strains were able to grow and produce gliotoxin onto the studied conditions including the lung ones. Environmental and clinical strains were physiologically similar and could be an important putative infection source in rural workers. PMID- 26551058 TI - A SPRINT to the Finish. PMID- 26551059 TI - Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. AB - Optogenetics allows rapid, temporally specific control of neuronal activity by targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose considerable physical constraints on natural behaviors. In this report we bypass these limitations using technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliques that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain. PMID- 26551060 TI - Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors. AB - Genome editing with targeted nucleases and DNA donor templates homologous to the break site has proven challenging in human hematopoietic stem and progenitor cells (HSPCs), and particularly in the most primitive, long-term repopulating cell population. Here we report that combining electroporation of zinc finger nuclease (ZFN) mRNA with donor template delivery by adeno-associated virus (AAV) serotype 6 vectors directs efficient genome editing in HSPCs, achieving site specific insertion of a GFP cassette at the CCR5 and AAVS1 loci in mobilized peripheral blood CD34+ HSPCs at mean frequencies of 17% and 26%, respectively, and in fetal liver HSPCs at 19% and 43%, respectively. Notably, this approach modified the CD34+CD133+CD90+ cell population, a minor component of CD34+ cells that contains long-term repopulating hematopoietic stem cells (HSCs). Genome edited HSPCs also engrafted in immune-deficient mice long-term, confirming that HSCs are targeted by this approach. Our results provide a strategy for more robust application of genome-editing technologies in HSPCs. PMID- 26551061 TI - Calmodulin inhibition regulates morphological and functional changes related to the actin cytoskeleton in pure microglial cells. AB - The roles of calmodulin (CaM), a multifunctional intracellular calcium receptor protein, as concerns selected morphological and functional characteristics of pure microglial cells derived from mixed primary cultures from embryonal forebrains of rats, were investigated through use of the CaM antagonists calmidazolium (CALMID) and trifluoperazine (TFP). The intracellular localization of the CaM protein relative to phalloidin, a bicyclic heptapeptide that binds only to filamentous actin, and the ionized calcium-binding adaptor molecule 1 (Iba1), a microglia-specific actin-binding protein, was determined by immunocytochemistry, with quantitative analysis by immunoblotting. In unchallenged and untreated (control) microglia, high concentrations of CaM protein were found mainly perinuclearly in ameboid microglia, while the cell cortex had a smaller CaM content that diminished progressively deeper into the branches in the ramified microglia. The amounts and intracellular distributions of both Iba1 and CaM proteins were altered after lipopolysaccharide (LPS) challenge in activated microglia. CALMID and TFP exerted different, sometimes opposing, effects on many morphological, cytoskeletal and functional characteristics of the microglial cells. They affected the CaM and Iba1 protein expressions and their intracellular localizations differently, inhibited cell proliferation, viability and fluid-phase phagocytosis to different degrees both in unchallenged and in LPS-treated (immunologically challenged) cells, and differentially affected the reorganization of the actin cytoskeleton in the microglial cell cortex, influencing lamellipodia, filopodia and podosome formation. In summary, these CaM antagonists altered different aspects of filamentous actin-based cell morphology and related functions with variable efficacy, which could be important in deciphering the roles of CaM in regulating microglial functions in health and disease. PMID- 26551062 TI - Evidence for the protective effects of curcumin against oxyhemoglobin-induced injury in rat cortical neurons. AB - Curcumin (CCM) is a natural polyphenolic compound in Curcuma longa that has been reported to exhibit neuroprotective effects. Subarachnoid hemorrhage (SAH) is a severe neurological disorder with an unsatisfactory prognosis. Oxyhemoglobin (OxyHb) plays an important role in mediating the neurological deficits following SAH. The present study, therefore, aimed to investigate the effect of CCM on primary cortical neurons exposed to OxyHb neurotoxicity. Cortical neurons were exposed to OxyHb at a concentration of 10 MUM in the presence or absence of 5 MUM (low dose) or 10 MUM (high dose) CCM for 24 h. Morphological changes in the neurons were observed. Cell viability and lactate dehydrogenase (LDH) release were assayed to determine the extent of cell injury. Additionally, levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH Px), and reactive oxygen species (ROS) were measured. Neuronal apoptosis was assayed via TUNEL staining and protein levels of cleaved caspase-3, Bax, and Bcl 2 were measured by Western blot. Levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and IL-6 were measured using ELISA kits. Our results suggested that CCM at both low and high doses markedly improved cell viability and decreased LDH release. CCM treatment decreased neuronal apoptosis. Additionally, oxidative stress and inflammation induced by OxyHb were alleviated by CCM treatment. In conclusion, CCM inhibits neuronal apoptosis, and alleviates oxidative stress and inflammation in neurons subjected to OxyHb, suggesting that it may be beneficial in the treatment of brain damage following SAH. PMID- 26551063 TI - Intracellular mechanisms involved in copper-gonadotropin-releasing hormone (Cu GnRH) complex-induced cAMP/PKA signaling in female rat anterior pituitary cells in vitro. AB - The copper-gonadotropin-releasing hormone molecule (Cu-GnRH) is a GnRH analog, which preserves its amino acid sequence, but which contains a Cu(2+) ion stably bound to the nitrogen atoms including that of the imidazole ring of Histidine(2). A previous report indicated that Cu-GnRH was able to activate cAMP/PKA signaling in anterior pituitary cells in vitro, but raised the question of which intracellular mechanism(s) mediated the Cu-GnRH-induced cAMP synthesis in gonadotropes. To investigate this mechanism, in the present study, female rat anterior pituitary cells in vitro were pretreated with 0.1 MUM antide, a GnRH antagonist; 0.1 MUM cetrorelix, a GnRH receptor antagonist; 0.1 MUM PACAP6-38, a PAC-1 receptor antagonist; 2 MUM GF109203X, a protein kinase C inhibitor; 50 mM PMA, a protein kinase C activator; the protein kinase A inhibitors H89 (30 MUM) and KT5720 (60 nM); factors affecting intracellular calcium activity: 2.5 mM EGTA; 2 MUM thapsigargin; 5 MUM A23187, a Ca(2+) ionophore; or 10 MUg/ml cycloheximide, a protein synthesis inhibitor. After one of the above pretreatments, cells were incubated in the presence of 0.1 MUM Cu-GnRH for 0.5, 1, and 3 h. Radioimmunoassay analysis of cAMP confirmed the functional link between Cu-GnRH stimulation and cAMP/PKA signal transduction in rat anterior pituitary cells, demonstrating increased intracellular cAMP, which was reduced in the presence of specific PKA inhibitors. The stimulatory effect of Cu-GnRH on cAMP production was partly dependent on GnRH receptor activation. In addition, an indirect and Ca(2+)-dependent mechanism might be involved in intracellular adenylate cyclase stimulation. Neither activation of protein kinase C nor new protein synthesis was involved in the Cu-GnRH-induced increase of cAMP in the rat anterior pituitary primary cultures. Presented data indicate that conformational changes of GnRH molecule resulting from cooper ion coordination affect specific pharmacological properties of Cu-GnRH molecule including specific pattern of intracellular activity induced by complex in anterior pituitary cells in vitro. PMID- 26551064 TI - Neurotrophic effects of amyloid precursor protein peptide 165 in vitro. AB - Diabetic encephalopathy is one of the risk factors for Alzheimer's disease. Our previous findings indicated that animals with diabetic encephalopathy exhibit learning and memory impairment in addition to hippocampal neurodegeneration, both of which are ameliorated with amyloid precursor protein (APP) 17-mer (APP17) peptide treatment. Although APP17 is neuroprotective, it is susceptible to enzymatic degradation. Derived from the active sequence structure of APP17, we have previously structurally transformed and modified several APP5-mer peptides (APP328-332 [RERMS], APP 5). We have developed seven different derivatives of APP5, including several analogs. Results from the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay on human neuroblastoma SH-SY5Y cells in the present study showed that P165 was the most neuroprotective APP5 derivative. Furthermore, we tested the effects of APP5 and P165 on the number of cells and the release of lactate dehydrogenase. Western immunoblot analyses were also performed. The digestion rates of P165 and APP5 were determined by the pepsin digestion test. P165 resisted pepsin digestion significantly more than APP5. Therefore, P165 may be optimal for oral administration. Overall, these findings suggest that P165 may be a potential drug for the treatment of diabetic encephalopathy. PMID- 26551065 TI - Triazole double-headed ribonucleosides as inhibitors of eosinophil derived neurotoxin. AB - Eosinophil derived neurotoxin (EDN) is an eosinophil secretion protein and a member of the Ribonuclease A (RNase A) superfamily involved in the immune response system and inflammatory disorders. The pathological actions of EDN are strongly dependent on the enzymatic activity and therefore, it is of significant interest to discover potent and specific inhibitors of EDN. In this framework we have assessed the inhibitory potency of triazole double-headed ribonucleosides. We present here an efficient method for the heterologous production and purification of EDN together with the synthesis of nucleosides and their biochemical evaluation in RNase A and EDN. Two groups of double-headed nucleosides were synthesized by the attachment of a purine or a pyrimidine base, through a triazole group at the 3'-C position of a pyrimidine or a purine ribonucleoside, respectively. Based on previous data with mononucleosides these compounds were expected to improve the inhibitory potency for RNase A and specificity for EDN. Kinetics data revealed that despite the rational, all but one, double-headed ribonucleosides were less potent than the respective mononucleosides while they were also more specific for ribonuclease A than for EDN. Compound 11c (9-[3'-[4-[(cytosine-1-yl)methyl]-1,2,3-triazol-1-yl]-beta-d ribofuranosyl]adenine) displayed a stronger preference for EDN than for ribonuclease A and a Ki value of 58MUM. This is the first time that an inhibitor is reported to have a better potency for EDN than for RNase A. The crystal structure of EDN-11c complex reveals the structural basis of its potency and selectivity providing important guidelines for future structure-based inhibitor design efforts. PMID- 26551067 TI - Novel Technique: Knee Arthrodesis Using Trabecular Metal Cones with Intramedullary Nailing and Intramedullary Autograft. AB - The failed total knee arthroplasty is a challenge to the surgeon and the patient. Infection, bone loss, and instability lead to a chronically painful and dysfunctional limb. Two-stage revision arthroplasty has been successful in clearing a majority of periprosthetic joint infections. However, there are many cases when the multiply revised and infected total knee arthroplasty cannot be salvaged. We report, a review of knee arthrodesis and a novel technique to manage significant bone loss. The use of trabecular metal cones and a long intramedullary nail can be used in concert with an autologous intramedullary bone graft to provide a stable, length restoring construct with sufficient biology to heal very large bone voids. With this technique we have successfully restored function and stability in the failed knee arthroplasty. PMID- 26551066 TI - Effect of Sodium Hyaluronate on Recovery after Arthroscopic Knee Surgery. AB - The aim of this study was to evaluate the effect of a single immediate postoperative instillation of 10 mL of sodium hyaluronate (Viscoseal) into the knee following arthroscopy. A single-center, prospective, randomized, controlled study was undertaken. Consenting knee arthroscopy patients were randomized into two groups following surgery: the study group received 10 mL of sodium hyaluronate intra-articularly, while the control group received an intra articular instillation of 10 mL of Bupivacaine. Pre- and postoperative visual analogue scale scores for pain and Western Ontario and McMaster Universities (WOMAC) scores for knee function were obtained. Overall, 48 patients under the care of a single surgeon were randomized into two groups of 24. There were no statistically significant demographic differences at baseline. Three patients were lost to follow-up. There was a statistically significant difference in pain scores favoring the study group compared with the control group at 3 and 6 weeks postoperatively (p < 0.05), and a statistically significant difference in WOMAC scores favoring the study group compared with the control group at 3 and 6 weeks postoperatively (p = 0.01). Synovial fluid replacement with sodium hyaluronate following arthroscopic knee surgery conferred statistically significant improvements in pain and function scores compared with Bupivacaine in the short term (3-6 weeks). PMID- 26551068 TI - Pulmonary Findings on Computed Tomography in Asymptomatic Total Joint Arthroplasty Patients. AB - An increase in the diagnosis of pulmonary embolus (PE) in the early postoperative period has been attributed to the use of multidetector 64-slice computed tomographic (CT) scans. It was suspected that this finding was the result of marrow or fat emboli that are commonly associated with arthroplasty rather than a true venous thromboembolic phenomenon. The purpose of this study was to determine the baseline pulmonary findings in asymptomatic patients after total joint arthroplasty (TJA). Over a 1-year period, an institutional review board-approved prospective study of 20 asymptomatic patients using a multidetector 64-slice CT scanner was performed. Overall, 15 TKAs and 5 total hip arthroplasties were included for analysis. All of the CT scans were negative for PE. There were no signs of microemboli or fat emboli on any scan. No patient went on to develop a PE at 2 years postoperatively. Despite the fact that emboli are created during TJA, if emboli are seen on a CT scan postoperatively, they should be assumed to be real events with clinical sequelae. If pulmonary symptoms develop postoperatively, they should not simply be assumed to be the result of fat or marrow embolism. PMID- 26551069 TI - Management of Posterior Articular Depression in Tibial Plateau Fractures. AB - Fractures involving the posterior aspect of the tibial plateau are challenging fractures to treat. Articular depression in tibial plateau fractures is usually addressed by elevation of the fragment(s), filling the residual defect with bone graft or bone substitute, and "raft" support of the articular fracture reduction with screws through a medially and/or laterally based plate. Posterior tibial plateau articular depression presents unique challenges for obtaining and maintaining fracture reduction. To obtain the goals of anatomic reduction and stable fixation, a thorough understanding of the fracture, specific approaches, reduction techniques, and stabilization strategies is needed. This article reviews the most current strategies for treating tibial plateau fracture patients with posterior articular depression. PMID- 26551070 TI - Limited Added Value of the Posterolateral Approach. AB - BACKGROUND: Posterolateral tibial plateau fractures (AO/OTA 41-B or 41-C) represent a minority of proximal tibia fractures. Numerous surgical approaches have been described, each with unique variations and limitations. The purpose of this study is to quantitatively and qualitatively compare the surface area and structures exposed by four surgical approaches to the posterolateral proximal tibia. METHODS: Four published surgical approaches-direct posterolateral (DPL), transfibular (TF), posteromedial (PM), and anterolateral (AL)-were performed on 10 fresh-frozen cadavers. Once each exposure was obtained, a ruler was placed in the surgical field and calibrated digital images obtained. Overall, 10 bony and soft tissue landmarks were identified and the surgeon's ability to see or touch each landmark was recorded sequentially for each exposure. RESULTS: An average of 3.9 +/- 2.7 cm(2) of posterolateral proximal tibial cortex was exposed by the DPL approach with significantly more surface area exposed by the TF, PM, and AL approaches (p < 0.01). The AL and PM approaches revealed a significantly larger area of tibial metaphysis and, when used together, consistently exposed posterior metaphyseal and intra-articular structures. CONCLUSION: A combination of the AL and PM approaches allows comparable surgical exposure to the proximal tibial when compared with two posterolateral approaches. These approaches can be employed together for reduction and fixation of injuries to the posterolateral tibial plateau and allow direct evaluation of the articular surface. Dedicated posterolateral approaches should be reserved for certain clinical situations, including proximal tibiofibular joint fracture or dislocation. PMID- 26551071 TI - Possible contributing role of Epstein-Barr virus (EBV) as a cofactor in human papillomavirus (HPV)-associated cervical carcinogenesis. AB - BACKGROUND: Persistent infection with EBV has been linked to the development of malignancies including HPV-associated cervical carcinoma. However, the role of EBV in HPV-associated cervical cancer is still poorly understood. OBJECTIVE: To determine the possible contributing role of EBV in HPV-associated cervical carcinogenesis according to HPV genotypes, HPV genome status and EBV localization. STUDY DESIGN: Cervical tissues, including 82 with no squamous intraepithelial lesions (noSILs), 85 low-grade SILs (LSILs), 85 high grade SILs (HSILs) and 40 squamous cell carcinoma samples (SCC) were investigated using PCR and dot blot hybridization for EBV detection and PCR and reverse line blot hybridization for HPV genotyping. The amplification of papillomavirus oncogene transcripts assay and in situ hybridization were used to determine HPV physical status and EBV EBER localization, respectively. RESULTS: EBV was detected increasingly from noSIL (13.4%), LSIL (29.4%) to HSIL (49.4%) samples. The prevalence of HPV-EBV co-infection was significantly higher in any grade of lesion than in noSIL samples (p<0.05) including noSIL (1.2%; 95% confidence intervals [CI]=0.0-3.6%, relative risk [RR]=1), LSIL (18.8%, 95% CI=10.5-27.1%, RR=15.4), HSIL (41.2%, 95% CI=30.7-51.6%, RR=33.8) and SCC (30.0%, 95% CI=15.8 44.2%, RR=24.6). Interestingly, HPV-EBV co-infection was more common in cases with episomal forms of high-risk (HR) HPV whereas HPV alone was more common in cases with integrated HR-HPV. In addition, EBER staining demonstrated that EBV was mainly present in infiltrating lymphocytes. CONCLUSION: Infiltrating EBV infected lymphocytes may play a role in cancer progression of cervical lesion containing episomal HR-HPV. PMID- 26551073 TI - Treating agitation and aggression in patients with Alzheimer's disease with escitalopram. PMID- 26551074 TI - The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST complex. AB - Tetrahymena telomerase holoenzyme subunits p75, p45 and p19 form a subcomplex (7 4-1) peripheral to the catalytic core. We report structures of p45 and p19 and reveal them as the Stn1 and Ten1 subunits of the CST complex, which stimulates telomerase complementary-strand synthesis. 7-4-1 binds telomeric single-stranded DNA, and mutant p19 overexpression causes telomere 3'-overhang elongation. We propose that telomerase-tethered Tetrahymena CST coordinates telomere G-strand and C-strand synthesis. PMID- 26551072 TI - Mechanisms of divalent metal toxicity in affective disorders. AB - Metals are required for proper brain development and play an important role in a number of neurobiological functions. The divalent metal transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress promoted by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID- 26551075 TI - EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src. AB - Aberrant activation of the EGF receptor (EGFR) contributes to many human cancers by activating the Ras-MAPK pathway and other pathways. EGFR signaling is augmented by Src-family kinases, but the mechanism is poorly understood. Here, we show that human EGFR preferentially phosphorylates peptide substrates that are primed by a prior phosphorylation. Using peptides based on the sequence of the adaptor protein Shc1, we show that Src mediates the priming phosphorylation, thus promoting subsequent phosphorylation by EGFR. Importantly, the doubly phosphorylated Shc1 peptide binds more tightly than singly phosphorylated peptide to the Ras activator Grb2; this binding is a key step in activating the Ras-MAPK pathway. Finally, a crystal structure of EGFR in complex with a primed Shc1 peptide reveals the structural basis for EGFR substrate specificity. These results provide a molecular explanation for the integration of Src and EGFR signaling with downstream effectors such as Ras. PMID- 26551076 TI - R loops regulate promoter-proximal chromatin architecture and cellular differentiation. AB - Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R loops, RNA-DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin-regulatory complexes, Tip60-p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60-p400 histone acetyltransferase complex binds to nascent transcripts; however, transcription promotes chromatin binding of Tip60 p400 but not PRC2. Interestingly, we observed higher Tip60-p400 and lower PRC2 levels at genes marked by promoter-proximal R loops. Furthermore, disruption of R loops broadly decreased Tip60-p400 occupancy and increased PRC2 occupancy genome wide. In agreement with these alterations, ESCs partially depleted of R loops exhibited impaired differentiation. These results show that R loops act both positively and negatively in modulating the recruitment of key pluripotency regulators. PMID- 26551078 TI - Nuclear staining of fgfr-2/stat-5 and runx-2 in mucinous breast cancer. AB - Mucinous carcinoma (MBC) is a rare subtype of breast cancer characterized by the production of variable amounts of mucin, with a prognosis better than that of non mucinous carcinomas (NMBC). The aim of this project was to evaluate the expression of STAT-5, RUNX-2, and FGFR-2 in a cohort of MBC and compare it with that of NMBC using standard immunohistochemistry. STAT-5 and RUNX-2 are two transcription factors with cytoplasmic and/or nuclear localization that have been related to FGFR-2, a tyrosine kinase growth factor receptor that can interact with STAT-5 and with PR in the nuclei of breast cancer cells. Membranous, cytoplasmic, and nuclear staining were evaluated and expressed as the percentage of stained cells (0-100%) multiplied by the staining intensity (0-3), thus obtaining an index ranging from 0 to 300. Nuclear and/or cytoplasmic immunoreactivity of the three proteins were detected in a high number of NMBC. Nuclear FGFR-2 staining correlated with nuclear STAT-5 (p<0.05) and nuclear RUNX 2 (p<0.01) in both tumor types; however MBC had a significant higher expression of nuclear FGFR-2 (p<0.01) and RUNX-2 (p<0.05) than that of NMBC, and displayed positive immunoreactivity of the 3 proteins in 70.8% of the cases. These results suggest that these proteins may have a role in the progression of the mucinous phenotype, in which nuclear STAT-5 may inhibit RUNX-2 prometastatic effect. PMID- 26551079 TI - Susceptibility of monocytes to activation correlates with atherogenic mitochondrial DNA mutations. AB - We have recently evaluated the susceptibility of circulating monocytes to pro- and anti-inflammatory activation comparing samples from healthy individuals and patients with asymptomatic carotid atherosclerosis. Surprisingly, we found a dramatic individual difference in susceptibility to activation between monocytes isolated from the blood of different subjects, regardless of the presence or absence of atherosclerosis. In the present study the monocyte susceptibility to pro-inflammatory activation was evaluated in comparison with mitochondrial DNA mutations that have previously been shown to correlate with the degree of carotid atherosclerosis assessed by intima-media thickness. Among the mutations associated with atherosclerosis were both homoplasmic (absence or presence of the mutation) or heteroplasmic (different proportions of mutant allele). It was found that two homoplasmic mutations, A1811G and G9477A, tended to correlate with the degree of monocyte susceptibility to activation. At the same time, the mutation G9477A inversely correlated with the degree of monocyte activability, that is, the mutation was more prevalent in monocytes with a low degree of activability. We have found that at least three heteroplasmic mutations of mtDNA (G14459A, A1555G, G12315A) earlier known to be associated with human atherosclerosis, also correlate with proinflammatory activation of circulating human monocytes. We suggest that some mutations can cause mitochondrial dysfunction, which in turn may lead to changes of macrophage activities in atherosclerosis. PMID- 26551077 TI - The role of lipids in mechanosensation. AB - The ability of proteins to sense membrane tension is pervasive in biology. A higher-resolution structure of the Escherichia coli small-conductance mechanosensitive channel MscS identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids, and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (with two acyl chains) from MscS pockets and trigger channel opening. We propose that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS. When interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable, and the channel gates. PMID- 26551080 TI - Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways. AB - In the present study, chemopreventive efficacy of hesperidin was evaluated against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in wistar rats. Nephrotoxicity was induced by single intraperitoneal injection of Fe-NTA (9 mg Fe/kg b.wt). Renal cancer was initiated by the administration of N-nitrosodiethylamine (DEN 200mg/kg b.wt ip) and promoted by Fe-NTA (9 mg Fe/kg b.wt ip) twice weekly for 16 weeks. Efficacy of hesperidin against Fe-NTA-induced nephrotoxicity was assessed in terms of biochemical estimation of antioxidant enzyme activities viz. reduced renal GSH, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, superoxide dismutase and renal toxicity markers (BUN, Creatinine, KIM 1). Administration of Fe-NTA significantly depleted antioxidant renal armory, enhanced renal lipid peroxidation as well as the levels of BUN, creatinine and KIM-1. However, simultaneous pretreatment of hesperidin restored their levels in a dose dependent manner. Expression of apoptotic markers caspase-3, caspase-9, bax, bcl-2 and proliferative marker PCNA along with inflammatory markers (NFkappaB, iNOS, TNF-alpha) were also analysed to assess the chemopreventive potential of hesperidin in two-stage renal carcinogenesis model. Hesperidin was found to induce caspase-3, caspase-9, bax expression and downregulate bcl-2, NFkappaB, iNOS, TNF-alpha, PCNA expression. Histopathological findings further revealed hesperidin's chemopreventive efficacy by restoring the renal morphology. Our results provide a powerful evidence suggesting hesperidin to be a potent chemopreventive agent against renal carcinogenesis possibly by virtue of its antioxidant properties and by modulation of multiple molecular pathways. PMID- 26551081 TI - The influence of DNA degradation in formalin-fixed, paraffin-embedded (FFPE) tissue on locus-specific methylation assessment by MS-HRM. AB - Readily accessible formalin-fixed paraffin embedded (FFPE) tissues are a highly valuable source of genetic material for molecular analyses in both research and in vitro diagnostics but frequently genetic material in those samples is highly degraded. With locus-specific methylation changes being widely investigated for use as biomarkers in various aspects of clinical disease management, we aimed to evaluate to what extent standard laboratory procedures can approximate the quality of the DNA extracted from FFPE samples prior to methylation analyses. DNA quality in 107 FFPE non-small cell lung cancer (NSCLC) samples was evaluated using spectrophotometry and gel electrophoresis. Subsequently, the quality assessment results were correlated with the results of locus specific methylation assessment with methylation sensitive high resolution melting (MS-HRM). The correlation of template quality with PCR amplification performance and HRM based methylation detection indicated a significant influence of DNA quality on PCR amplification but not on methylation assessment. In conclusion, standard laboratory procedures fairly well approximate DNA degradation of FFPE samples and DNA degradation does not seem to considerably affect locus-specific methylation assessment by MS-HRM. PMID- 26551082 TI - CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer. AB - BACKGROUND: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. METHODS: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. RESULTS: A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right sided tumors (p<0.05), poorly differentiated tumors (p<0.05), and MMR-deficient tumors (p<0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p<0.01), poorly differentiated tumors (p<0.001), and MMR deficient tumors (p<0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. CONCLUSION: We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated. PMID- 26551083 TI - Neutrophil's weapons in atherosclerosis. AB - Neutrophils are important components of immunity associated with inflammatory responses against a broad spectrum of pathogens. These cells could be rapidly activated by proinflammatory stimuli and migrate to the inflamed and infected sites where they release a variety of cytotoxic molecules with antimicrobial activity. Neutrophil antibacterial factors include extracellular proteases, redox enzymes, antimicrobial peptides, and small bioactive molecules. In resting neutrophils, these factors are stored in granules and released upon activation during degranulation. These factors could be also secreted in a neutrophil derived microparticle-dependent fashion. Neutrophils exhibit a unique property to produce neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins to catch and kill bacteria. Neutrophil-released factors are efficient in inactivation and elimination of pathogens through oxidation dependent or independent damage of bacterial cells, inactivation and neutralization of virulence factors and other mechanisms. However, in chronic atherosclerosis-associated inflammation, protective function of neutrophils could be impaired and misdirected against own cells. This could lead to deleterious effects and progressive vascular injury. In atherogenesis, a pathogenic role of neutrophils could be especially seen in early stages associated with endothelial dysfunction and induction of vascular inflammation and in late atherosclerosis associated with plaque rupture and atherothrombosis. Assuming a prominent impact of neutrophils in cardiovascular pathology, developing therapeutic strategies targeting neutrophil-specific antigens could have a promising clinical potential. PMID- 26551084 TI - Reactive protoplasmic and fibrous astrocytes contain high levels of calpain cleaved alpha 2 spectrin. AB - Calpain, a family of calcium-dependent neutral proteases, plays important roles in neurophysiology and pathology through the proteolytic modification of cytoskeletal proteins, receptors and kinases. Alpha 2 spectrin (alphaII spectrin) is a major substrate for this protease family, and the presence of the alphaII spectrin breakdown product (alphaIotaIota spectrin BDP) in a cell is evidence of calpain activity triggered by enhanced intracytoplasmic Ca(2+) concentrations. Astrocytes, the most dynamic CNS cells, respond to micro-environmental changes or noxious stimuli by elevating intracytoplasmic Ca(2+) concentration to become activated. As one measure of whether calpains are involved with reactive glial transformation, we examined paraffin sections of the human cerebral cortex and white matter by immunohistochemistry with an antibody specific for the calpain mediated alphaIotaIota spectrin BDP. We also performed conventional double immunohistochemistry as well as immunofluorescent studies utilizing antibodies against alphaIotaIota spectrin BDP as well as glial fibrillary acidic protein (GFAP). We found strong immunopositivity in selected protoplasmic and fibrous astrocytes, and in transitional forms that raise the possibility of some of fibrous astrocytes emerging from protoplasmic astrocytes. Immunoreactive astrocytes were numerous in brain sections from cases with severe cardiac and/or respiratory diseases in the current study as opposed to our previous study of cases without significant clinical conditions that failed to reveal such remarkable immunohistochemical alterations. Our study suggests that astrocytes become alphaIotaIota spectrin BDP immunopositive in various stages of activation, and that spectrin cleavage product persists even in fully reactive astrocytes. Immunohistochemistry for alphaIotaIota spectrin BDP thus marks reactive astrocytes, and highlights the likelihood that calpains and their proteolytic processing of spectrin participate in the morphologic and physiologic transition from resting protoplasmic astrocytes to reactive fibrous astrocytes. PMID- 26551086 TI - Pituitary adenoma-neuronal choristoma is a pituitary adenoma with ganglionic differentiation. AB - The presence of ganglion cells within an endocrine pituitary tumor has been named hamartoma, choristoma, gangliocytoma, or most recently pituitary adenoma-neuronal choristoma (PANCH). The presence of neuronal differentiation in regular pituitary adenomas has been previously suggested, however, its origin, the extent of its presence, and the relationship between the neuronal elements and the pituitary adenoma remain uncertain. Thus, to further explore the neuronal potential of pituitary tumors, we used immunohistochemistry on pituitary tumors of different grades, with a neuronal antigen protein (NeuN) antibody as a specific marker for mature neuronal differentiation. We found NeuN expression in 26.47% (9/34) cases of pituitary tumors without ganglionic differentiation (7 adenomas, 1 atypical adenoma and 1 pituitary carcinoma), in addition to NeuN expression in pituitary adenomas with ganglionic cells (2/2). Thus, neuronal expression is an innate property of pituitary adenomas. We propose that the rare presence of ganglionic cells in pituitary adenomas is not the result of a separate lesion or "collision sellar tumors", as previously suggested, but a ganglionic neuronal differentiation in an endocrine neoplasm. The ganglionic cells may be arising from uncommitted stem/progenitor cells that contain both neuronal and endocrine properties. A label of "pituitary adenoma with ganglionic differentiation" would better reflect the dual differentiation in a neuroendocrine tumor than the current label "PANCH". PMID- 26551085 TI - Induction of CYP2E1 in non-alcoholic fatty liver diseases. AB - Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 was elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids. PMID- 26551087 TI - Multinucleated giant cells in atherosclerotic plaques of human carotid arteries: Identification of osteoclast-like cells and their specific proteins in artery wall. AB - The mechanism(s) mediating atherosclerotic calcification may be similar to those governing bone remodeling, and osteoblast-like cells have been observed in plaque. We tested the hypothesis that osteoclast-like cells (OLCs) also exist in atherosclerotic arteries. In 205 tissue blocks obtained from 21 patients undergoing carotid endarterectomy, we performed histopathologic analysis, histochemical staining for tartrate-resistant acid phosphatase (TRAP), and immunohistochemical analysis for osteoclast and macrophage antigens, including CD68, colony stimulating factor-1 receptor (CSF-1R), cathepsin K (cat-K), receptor activator of nuclear factor-kappaB (RANK), and osteoprotegerin (OPG). Lesions were classified according to the AHA system, and further grouped as calcified or non-calcified (with necrotic cores or suture granulomas). Multinucleated giant cells morphologically similar to osteoclasts were frequently seen, sometimes exhibited morphologic evidence of polarization, were closely associated with regions of calcification, fibrosis, or granulomatous tissue, and also appeared to be associated with neovascularization and regions of intraplaque hemorrhage. TRAP-positive cells often expressed the osteoclast-associated antigens cat-K, RANK, and OPG. Calcification typically occurred at the base of plaque or in necrotic cores in various morphologies, including a fine powdery pattern, a diffuse pattern of larger deposits near cholesterol clefts and necrotic centers, and nodular forms. Regions of frank ossification were rarely observed. CONCLUSION: OLCs are frequently found in plaque, and co-localize with sub-regions of cholesterol deposition, mineralization, and necrotic and foreign debris. True bone tissue is rare in carotid plaque, although more common in other arteries. Our findings suggest that arterial OLCs might degrade mineral deposits, prevent formation of calcification or both and therefore counterbalance the activity of the osteoblast-like cells in atherosclerosis. PMID- 26551088 TI - Observational Evidence for Involvement of Nitrate Radicals in Nighttime Oxidation of Mercury. AB - In the atmosphere, reactive forms of mercury species can be produced by oxidation of the dominant gaseous elemental mercury (GEM). The oxidation of GEM is an important driver for deposition, but oxidation pathways currently are poorly constrained and likely differ among regions. In this study, continuous measurements of atmospheric nitrate radical (NO3) concentrations and mercury speciation (i.e., elemental and reactive, oxidized forms) were performed during a six week period in the urban air shed of Jerusalem, Israel during summer 2012, to investigate the potential nighttime contribution of nitrate radicals to oxidized mercury formation. Average nighttime concentrations of reactive gaseous mercury (RGM) were almost equivalent to daytime levels (25 pg m(-3) and 27 pg m(-3) respectively), in contrast to early morning and evening RGM levels which dropped to low levels (9 and 13 pg m(-3)). During daytime, the presence of RGM was increased when solar radiation exceeded 200 W m(-2), suggesting a photochemical process for daytime RGM formation. Ozone concentrations were largely unrelated to daytime RGM. Nighttime RGM concentrations were relatively high (with a maximum of 97 pg m(-3)) compared to nighttime levels in other urban regions. A strong correlation was observed between nighttime RGM concentrations and nitrate radical concentration (R(2) averaging 0.47), while correlations to other variables were weak (e.g., RH; R(2) = 0.35) or absent (e.g., ozone, wind speed and direction, pollution tracers such as CO or SO2). Detailed analyses suggest that advection processes or tropospheric influences were unlikely to explain the strong nighttime correlations between NO3 and RGM, although these processes may contribute to these relationships. Our observations suggest that NO3 radicals may play a role in RGM formation, possibly due to a direct chemical involvement in GEM oxidation. Since physical data, however, suggest that NO3 unlikely initiates GEM oxidation, NO3 may play a secondary role in GEM oxidation through the addition to an unstable Hg(I) radical species. PMID- 26551089 TI - Cognitive and Motor Aspects of Parkinson's Disease Associated with Dysphagia. AB - BACKGROUND: Dysphagia is a common symptom and an important prognostic factor in Parkinson's disease (PD). Although cognitive and motor dysfunctions may contribute to dysphagia in patients with PD, any specific association between such problems and swallowing functions is unclear. Here, we examined the potential relationship between cognitive/motor components and swallowing functions in PD. We evaluated the contributions of cognition and motor function to the components of swallowing via video fluoroscopic swallowing (VFS) experiments. METHODS: We prospectively enrolled 56 patients without dementia having PD. Parkinson's disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). All participants received neuropsychological tests covering general mental status, visuospatial function, attention, language, learning and memory, and frontal executive function. The well-validated "modified barium swallow impairment profile" scoring system was applied during VFS studies to quantify swallowing impairments. Finally, correlations between neuropsychological or motor functions and impairment in swallowing components were calculated. RESULTS: The most significant correlations were found between the frontal/executive or learning/memory domains and the oral phase of swallowing, though a minor component of the pharyngeal phase correlated with frontal function as well. Bradykinesia and the UPDRS total score were associated with both the pharyngeal and oral phases. CONCLUSIONS: Our findings suggest that cognitive dysfunctions are associated with the oral phase of swallowing in patients with early stage PD while the severity of motor symptoms may be associated with overall swallowing function. PMID- 26551090 TI - Dissecting Aneurysm of the Recurrent Artery of Heubner in a Patient With Osteogenesis Imperfecta. PMID- 26551092 TI - Unbounded Violation of Quantum Steering Inequalities. AB - We construct steering inequalities that exhibit unbounded violation. The concept was to exploit the relationship between steering violation and the uncertainty relation. To this end, we apply mutually unbiased bases and anticommuting observables, known to exhibit the strongest uncertainty. In both cases, we are able to procure unbounded violations. Our approach is much more constructive and transparent than the operator space theory approach employed to obtain large violation of Bell inequalities. Importantly, using anticommuting observables we are able to obtain a dichotomic steering inequality with unbounded violation. Thus far, there is no analogous result for Bell inequalities. Interestingly, both the dichotomic inequality and one of our inequalities cannot be directly obtained from existing uncertainty relations, which strongly suggest the existence of an unknown kind of uncertainty relation. PMID- 26551093 TI - Dynamics and Interaction of Vortex Lines in an Elongated Bose-Einstein Condensate. AB - We study the real-time dynamics of vortices in a large elongated Bose-Einstein condensate (BEC) of sodium atoms using a stroboscopic technique. Vortices are produced via the Kibble-Zurek mechanism in a quench across the BEC transition and they slowly precess keeping their orientation perpendicular to the long axis of the trap as expected for solitonic vortices in a highly anisotropic condensate. Good agreement with theoretical predictions is found for the precession period as a function of the orbit amplitude and the number of condensed atoms. In configurations with two or more vortices, we see signatures of vortex-vortex interaction in the shape and visibility of the orbits. In addition, when more than two vortices are present, their decay is faster than the thermal decay observed for one or two vortices. The possible role of vortex reconnection processes is discussed. PMID- 26551094 TI - Proposed Robust Entanglement-Based Magnetic Field Sensor Beyond the Standard Quantum Limit. AB - Recently, there have been significant developments in entanglement-based quantum metrology. However, entanglement is fragile against experimental imperfections, and quantum sensing to beat the standard quantum limit in scaling has not yet been achieved in realistic systems. Here, we show that it is possible to overcome such restrictions so that one can sense a magnetic field with an accuracy beyond the standard quantum limit even under the effect of decoherence, by using a realistic entangled state that can be easily created even with current technology. Our scheme could pave the way for the realizations of practical entanglement-based magnetic field sensors. PMID- 26551095 TI - Does the Collapse of a Supramassive Neutron Star Leave a Debris Disk? AB - One possible channel for black hole formation is the collapse of a rigidly rotating massive neutron star as it loses its angular momentum or gains excessive mass through accretion. It was proposed that part of the neutron star may form a debris disk around the black hole. Such short-lived massive disks could be the sources of powerful jets emitting cosmological gamma-ray bursts. Whether the collapse creates a disk depends on the equation of state of the neutron star. We survey a wide range of equations of states allowed by observations and find that disk formation is unfeasible. We conclude that this channel of black hole formation is incapable of producing powerful jets, and discuss implications for models of gamma-ray bursts. PMID- 26551096 TI - Emerging Hawking-Like Radiation from Gravitational Bremsstrahlung Beyond the Planck Scale. AB - We argue that, as a consequence of the graviton's spin-2, its bremsstrahlung in trans-Planckian-energy (E?M(P)) gravitational scattering at small deflection angle can be nicely expressed in terms of helicity-transformation phases and their transfer within the scattering process. The resulting spectrum exhibits deeply sub-Planckian characteristic energies of order M(P)(2)/E?M(P) (reminiscent of Hawking radiation), a suppressed fragmentation region, and a reduced rapidity plateau, in broad agreement with recent classical estimates. PMID- 26551091 TI - Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder. AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is characterized by a wide range of cognitive and behavioral abnormalities. Genetic research has identified large numbers of genes that contribute to ASD phenotypes. There is compelling evidence that environmental factors contribute to ASD through influences that differentially impact the brain through epigenetic mechanisms. Both genetic mutations and epigenetic influences alter gene expression in different cell types of the brain. Mutations impact the expression of large numbers of genes and also have downstream consequences depending on specific pathways associated with the mutation. Environmental factors impact the expression of sets of genes by altering methylation/hydroxymethylation patterns, local histone modification patterns and chromatin remodeling. Herein, we discuss recent developments in the research of ASD with a focus on epigenetic pathways as a complement to current genetic screening. PMID- 26551097 TI - Central Charges and the Sign of Entanglement in 4D Conformal Field Theories. AB - We explore properties of the universal terms in the entanglement entropy and logarithmic negativity in 4D conformal field theories, aiming to clarify the ways in which they behave like the analogous entanglement measures in quantum mechanics. We show that, unlike entanglement entropy in finite-dimensional systems, the sign of the universal part of entanglement entropy is indeterminate. In particular, if and only if the central charges obey a>c, the entanglement across certain classes of entangling surfaces can become arbitrarily negative, depending on the geometry and topology of the surface. The negative contribution is proportional to the product of a-c and the genus of the surface. Similarly, we show that in a>c theories, the logarithmic negativity does not always exceed the entanglement entropy. PMID- 26551098 TI - Continuous Multiscale Entanglement Renormalization Ansatz as Holographic Surface State Correspondence. AB - We present how the surface-state correspondence, conjectured by Miyaji and Takayanagi, works in the setup of AdS(3)/CFT(2) by generalizing the formulation of a continuous multiscale entanglement renormalization group ansatz. The boundary states in conformal field theories play a crucial role in our formulation and the bulk diffeomorphism is naturally taken into account. We give an identification of bulk local operators which reproduces correct scalar field solutions on AdS(3) and bulk scalar propagators. We also calculate the information metric for a locally excited state and show that it reproduces the time slice of AdS(3). PMID- 26551099 TI - Standard Model as a Double Field Theory. AB - We show that, without any extra physical degree introduced, the standard model can be readily reformulated as a double field theory. Consequently, the standard model can couple to an arbitrary stringy gravitational background in an O(4,4) T duality covariant manner and manifest two independent local Lorentz symmetries, Spin(1,3)*Spin(3,1). While the diagonal gauge fixing of the twofold spin groups leads to the conventional formulation on the flat Minkowskian background, the enhanced symmetry makes the standard model more rigid, and also stringy, than it appeared. The CP violating theta term may no longer be allowed by the symmetry, and hence the strong CP problem can be solved. There are now stronger constraints imposed on the possible higher order corrections. We speculate that the quarks and the leptons may belong to the two different spin classes. PMID- 26551100 TI - "Lagrangian" for a Non-Lagrangian Field Theory with N=2 Supersymmetry. AB - We suggest that at least some of the strongly coupled N=2 quantum field theories in 4D can have a nonconformal N=1 Lagrangian description flowing to them at low energies. In particular, we construct such a description for the N=2 rank one superconformal field theory with E(6) flavor symmetry, for which a Lagrangian description was previously unavailable. We utilize this description to compute several supersymmetric partition functions. PMID- 26551101 TI - Completing the Picture of the Roper Resonance. AB - We employ a continuum approach to the three valence-quark bound-state problem in relativistic quantum field theory to predict a range of properties of the proton's radial excitation and thereby unify them with those of numerous other hadrons. Our analysis indicates that the nucleon's first radial excitation is the Roper resonance. It consists of a core of three dressed quarks, which expresses its valence-quark content and whose charge radius is 80% larger than the proton analogue. That core is complemented by a meson cloud, which reduces the observed Roper mass by roughly 20%. The meson cloud materially affects long-wavelength characteristics of the Roper electroproduction amplitudes but the quark core is revealed to probes with Q(2)?3m(N)(2). PMID- 26551102 TI - Scalar Hint from the Diboson Excess? AB - In view of the recent diboson resonant excesses reported by both ATLAS and CMS Collaborations, we suggest that a new weak singlet pseudoscalar particle eta(WZ) may decay into two weak bosons while being produced in gluon fusion at the LHC. The couplings to the gauge bosons can arise from a Wess-Zumino-Witten anomaly term and thus we study an effective model based on the anomaly term as a well motivated phenomenological model. In models where the pseudoscalar particle arises as a composite state, the coefficients of the anomalous couplings can be related to the fermion components of the underlying dynamics. We provide an example to test the feasibility of the idea. PMID- 26551103 TI - Detecting Stealth Dark Matter Directly through Electromagnetic Polarizability. AB - We calculate the spin-independent scattering cross section for direct detection that results from the electromagnetic polarizability of a composite scalar "stealth baryon" dark matter candidate, arising from a dark SU(4) confining gauge theory-"stealth dark matter." In the nonrelativistic limit, electromagnetic polarizability proceeds through a dimension-7 interaction leading to a very small scattering cross section for dark matter with weak-scale masses. This represents a lower bound on the scattering cross section for composite dark matter theories with electromagnetically charged constituents. We carry out lattice calculations of the polarizability for the lightest "baryon" states in SU(3) and SU(4) gauge theories using the background field method on quenched configurations. We find the polarizabilities of SU(3) and SU(4) to be comparable (within about 50%) normalized to the stealth baryon mass, which is suggestive for extensions to larger SU(N) groups. The resulting scattering cross sections with a xenon target are shown to be potentially detectable in the dark matter mass range of about 200 700 GeV, where the lower bound is from the existing LUX constraint while the upper bound is the coherent neutrino background. Significant uncertainties in the cross section remain due to the more complicated interaction of the polarizablity operator with nuclear structure; however, the steep dependence on the dark matter mass, 1/m(B)(6), suggests the observable dark matter mass range is not appreciably modified. We briefly highlight collider searches for the mesons in the theory as well as the indirect astrophysical effects that may also provide excellent probes of stealth dark matter. PMID- 26551104 TI - Semivisible Jets: Dark Matter Undercover at the LHC. AB - Dark matter may be a composite particle that is accessible via a weakly coupled portal. If these hidden-sector states are produced at the Large Hadron Collider (LHC), they would undergo a QCD-like shower. This would result in a spray of stable invisible dark matter along with unstable states that decay back to the standard model. Such "semivisible" jets arise, for example, when their production and decay are driven by a leptophobic Z' resonance; the resulting signature is characterized by significant missing energy aligned along the direction of one of the jets. These events are vetoed by the current suite of searches employed by the LHC, resulting in low acceptance. This Letter will demonstrate that the transverse mass-computed using the final-state jets and the missing energy provides a powerful discriminator between the signal and the QCD background. Assuming that the Z' couples to the standard model quarks with the same strength as the Z(0), the proposed search can discover (exclude) Z' masses up to 2.5 TeV (3.5 TeV) with 100 fb(-1) of 14 TeV data at the LHC. PMID- 26551105 TI - Towards Exotic Hidden-Charm Pentaquarks in QCD. AB - Inspired by P(c)(4380) and P(c)(4450) recently observed by LHCb, a QCD sum rule investigation is performed, by which they can be identified as exotic hidden charm pentaquarks composed of an anticharmed meson and a charmed baryon. Our results suggest that P(c)(4380) and P(c)(4450) have quantum numbers J(P)=3/2(-) and 5/2(+), respectively. Furthermore, two extra hidden-charm pentaqurks with configurations DSigma(c)(*) and D(*)Sigma(c)(*) are predicted, which have spin parity quantum numbers J(P)=3/2(-) and J(P)=5/2(+), respectively. As an important extension, the mass predictions of hidden-bottom pentaquarks are also given. Searches for these partners of P(c)(4380) and P(c)(4450) are especially accessible at future experiments like LHCb and BelleII. PMID- 26551106 TI - (97)(37)Rb(60): The Cornerstone of the Region of Deformation around A ~ 100 [corrected]. AB - Excited states of the neutron-rich nuclei (97,99)Rb were populated for the first time using the multistep Coulomb excitation of radioactive beams. Comparisons of the results with particle-rotor model calculations provide clear identification for the ground-state rotational band of (97)Rb as being built on the pig(9/2) [431] 3/2(+) Nilsson-model configuration. The ground-state excitation spectra of the Rb isotopes show a marked distinction between single-particle-like structures below N=60 and rotational bands above. The present study defines the limits of the deformed region around A~100 and indicates that the deformation of (97)Rb is essentially the same as that observed well inside the deformed region. It further highlights the power of the Coulomb-excitation technique for obtaining spectroscopic information far from stability. The (99)Rb case demonstrates the challenges of studies with very short-lived postaccelerated radioactive beams. PMID- 26551108 TI - Pathway for the Production of Neutron-Rich Isotopes around the N=126 Shell Closure. AB - Absolute cross sections for isotopically identified products formed in multinucleon transfer in the (136)Xe+(198)Pt system at ~8 MeV/nucleon are reported. The isotopic distributions obtained using a large acceptance spectrometer demonstrated the production of the "hard-to-reach" neutron-rich isotopes for Z<78 around the N=126 shell closure far from stability. The main contribution to the formation of these exotic nuclei is shown to arise in collisions with a small kinetic energy dissipation. The present experimental finding corroborates for the first time recent predictions that multinucleon transfer reactions would be the optimum method to populate and characterize neutron-rich isotopes around N=126 which are crucial for understanding both astrophysically relevant processes and the evolution of "magic" numbers far from stability. PMID- 26551109 TI - Rydberg Excitation of a Single Trapped Ion. AB - We demonstrate excitation of a single trapped cold (40)Ca(+) ion to Rydberg levels by laser radiation in the vacuum ultraviolet at a wavelength of 122 nm. Observed resonances are identified as 3d(2)D(3/2) to 51F, 52F and 3d(2)D(5/2) to 64F. We model the line shape and our results imply a large state-dependent coupling to the trapping potential. Rydberg ions are of great interest for future applications in quantum computing and simulation, in which large dipolar interactions are combined with the superb experimental control offered by Paul traps. PMID- 26551110 TI - Simultaneous Measurement of the Three-Dimensional Orientation of Excitation and Emission Dipoles. AB - The emission properties of most fluorescent emitters, such as dye molecules or solid-state color centers, can be well described by the model of an oscillating electric dipole. However, the orientations of their excitation and emission dipoles are, in most cases, not parallel. Although single molecule excitation and emission dipole orientation measurements have been performed in the past, no experimental method has so far looked at the three-dimensional excitation and emission dipole geometry of individual emitters simultaneously. We present the first experimental study, using defocused imaging in conjunction with radially polarized excitation scanning, to measure both the excitation as well as emission dipole orientations of single molecules, which allows us to sample the distribution of their mutual orientation. We find an unexpectedly broad distribution of the angle between both dipoles which we attribute to the interaction between the observed molecules and the substrate they are immobilized on. PMID- 26551111 TI - Enhancement of Ultracold Molecule Formation Using Shaped Nanosecond Frequency Chirps. AB - We demonstrate that judicious shaping of a nanosecond-time-scale frequency chirp can dramatically enhance the formation rate of ultracold (87)Rb(2) molecules. Starting with ultracold (87)Rb atoms, we apply pulses of frequency-chirped light to first photoassociate the atoms into excited molecules and then, later in the chirp, deexcite these molecules into a high vibrational level of the lowest triplet state a (3)Sigma(u)(+). The enhancing chirp shape passes through the absorption and stimulated emission transitions relatively slowly, thus increasing their adiabaticity, but jumps quickly between them to minimize the effects of spontaneous emission. Comparisons with quantum simulations for various chirp shapes support this enhancement mechanism. PMID- 26551107 TI - Measurement of the Target-Normal Single-Spin Asymmetry in Quasielastic Scattering from the Reaction (3)He(?)(e,e'). AB - We report the first measurement of the target single-spin asymmetry, A(y), in quasielastic scattering from the inclusive reaction (3)He(?)(e,e') on a (3)He gas target polarized normal to the lepton scattering plane. Assuming time-reversal invariance, this asymmetry is strictly zero for one-photon exchange. A nonzero A(y) can arise from the interference between the one- and two-photon exchange processes which is sensitive to the details of the substructure of the nucleon. An experiment recently completed at Jefferson Lab yielded asymmetries with high statistical precision at Q(2)=0.13, 0.46, and 0.97 GeV(2). These measurements demonstrate, for the first time, that the (3)He asymmetry is clearly nonzero and negative at the 4sigma-9sigma level. Using measured proton-to-(3)He cross-section ratios and the effective polarization approximation, neutron asymmetries of -(1 3)% were obtained. The neutron asymmetry at high Q(2) is related to moments of the generalized parton distributions (GPDs). Our measured neutron asymmetry at Q(2)=0.97 GeV(2) agrees well with a prediction based on two-photon exchange using a GPD model and thus provides a new, independent constraint on these distributions. PMID- 26551112 TI - Attosecond Coherent Control of Single and Double Photoionization in Argon. AB - Ultrafast high harmonic beams provide new opportunities for coherently controlling excitation and ionization processes in atoms, molecules, and materials on attosecond time scales by employing multiphoton two-pathway electron wave-packet quantum interferences. Here we use spectrally tailored and frequency tuned vacuum and extreme ultraviolet harmonic combs, together with two phase locked infrared laser fields, to show how the total single and double photoionization yields of argon can be coherently modulated by controlling the relative phases of both optical and electronic-wave-packet quantum interferences. This Letter is the first to apply quantum control techniques to double photoionization, which is a fundamental process where a single, high-energy photon ionizes two electrons simultaneously from an atom. PMID- 26551113 TI - Nature of the Volume Isotope Effect in Ice. AB - The substitution of hydrogen (H) by deuterium (D) in ice Ih and in its H-ordered version, ice XI, produces an anomalous form of volume isotope effect (VIE), i.e., volume expansion. This VIE contrasts with the normal VIE (volume contraction) predicted in ice-VIII and in its H-disordered form, ice VII. Here we investigate the VIE in ice XI and in ice VIII using first principles quasiharmonic calculations. We conclude that normal and anomalous VIEs can be produced in ice VIII and ice XI in sequence by application of pressure (ice XI starting at negative pressures) followed by a third type-anomalous VIE with zero-point volume contraction. The latter should also contribute to the isotope effect in the ice VII -> ice X transition. The predicted change between normal and anomalous VIE in ice VIII at 14.3 GPa and 300 K is well reproduced experimentally in ice VII using x-ray diffraction measurements. The present discussion of the VIE is general, and conclusions should be applicable to other solid phases of H(2)O, possibly to liquid water under pressure, and to other H-bonded materials. PMID- 26551114 TI - Deviations from Boltzmann-Gibbs Statistics in Confined Optical Lattices. AB - We investigate the semiclassical phase-space probability distribution P(x,p) of cold atoms in a Sisyphus cooling lattice with an additional harmonic confinement. We pose the question of whether this nonequilibrium steady state satisfies the equivalence of energy and probability. This equivalence is the foundation of Boltzmann-Gibbs and generalized thermostatic statistics, and a prerequisite for the description in terms of a temperature. At large energies, P(x,p) depends only on the Hamiltonian H(x,p) and the answer to the question is yes. In distinction to the Boltzmann-Gibbs state, the large-energy tails are power laws P(x,p)?H(x,p)(-1/D), where D is related to the depth of the optical lattice. At intermediate energies, however, P(x,p) cannot be expressed as a function of the Hamiltonian and the equivalence between energy and probability breaks down. As a consequence the average potential and kinetic energy differ and no well-defined temperature can be assigned. The Boltzmann-Gibbs state is regained only in the limit of deep optical lattices. For strong confinement relative to the damping, we derive an explicit expression for the stationary phase-space distribution. PMID- 26551115 TI - Ultraefficient Coupling of a Quantum Emitter to the Tunable Guided Plasmons of a Carbon Nanotube. AB - We show that a single quantum emitter can efficiently couple to the tunable plasmons of a highly doped single-wall carbon nanotube (SWCNT). Plasmons in these quasi-one-dimensional carbon structures exhibit deep subwavelength confinement that pushes the coupling efficiency close to 100% over a very broad spectral range. This phenomenon takes place for distances and tube diameters comprising the nanometer and micrometer scales. In particular, we find a beta factor ~1 for QEs placed 1-100 nm away from SWCNTs that are just a few nanometers in diameter, while the corresponding Purcell factor exceeds 10(6). PMID- 26551116 TI - Blackbody Theory for Hyperbolic Materials. AB - The blackbody theory is revisited in the case of thermal electromagnetic fields inside uniaxial anisotropic media in thermal equilibrium with a heat bath. When these media are hyperbolic, we show that the spectral energy density of these fields radically differs from that predicted by Planck's blackbody theory and that the maximum of the spectral energy density determined by Wien's law is redshifted. Finally, we derive the Stefan-Boltzmann law for hyperbolic media which becomes a quadratic function of the heat bath temperature. PMID- 26551117 TI - Controlling Viscous Fingering Using Time-Dependent Strategies. AB - Control and stabilization of viscous fingering of immiscible fluids impacts a wide variety of pressure-driven multiphase flows. We report theoretical and experimental results on a time-dependent control strategy by manipulating the gap thickness b(t) in a lifting Hele-Shaw cell in the power-law form b(t)=b(1)t(1/7). Experimental results show good quantitative agreement with the predictions of linear stability analysis. By choosing the value of a single time-independent control parameter, we can either totally suppress the viscous fingering instability or maintain a series of nonsplitting viscous fingers during the fluid displacement process. In addition to the gap thickness of a Hele-Shaw cell, time dependent control strategies can, in principle, also be placed on the injection rate, viscosity of the displaced fluid, and interfacial tension between the two fluids. PMID- 26551118 TI - Evidence of Branching Phenomena in Current-Driven Ionization Waves. AB - This Letter reports the first fully consistent experimental observations of current-driven ionization waves conforming to the magnetohydrodynamic Rankine Hugoniot model for hydromagnetic shocks. Detailed measurements of the thermodynamic and electrodynamic plasma state variables across the ionization region confirm the existence of two types of waves, corresponding to the upper and lower solution branches of the Hugoniot curve. These waves are generated by pulsed currents in a coaxial gas-fed plasma accelerator. The coupling between the state variables of this complex, transient, three-dimensional system shows a remarkable quantitative agreement of less than 8% deviation from the quasisteady, one-dimensional theoretical model. PMID- 26551119 TI - Avoiding Tokamak Disruptions by Applying Static Magnetic Fields That Align Locked Modes with Stabilizing Wave-Driven Currents. AB - Nonrotating ("locked") magnetic islands often lead to complete losses of confinement in tokamak plasmas, called major disruptions. Here locked islands were suppressed for the first time, by a combination of applied three-dimensional magnetic fields and injected millimeter waves. The applied fields were used to control the phase of locking and so align the island O point with the region where the injected waves generated noninductive currents. This resulted in stabilization of the locked island, disruption avoidance, recovery of high confinement, and high pressure, in accordance with the expected dependencies upon wave power and relative phase between the O point and driven current. PMID- 26551120 TI - Generation of Large-Scale Magnetic Fields by Small-Scale Dynamo in Shear Flows. AB - We propose a new mechanism for a turbulent mean-field dynamo in which the magnetic fluctuations resulting from a small-scale dynamo drive the generation of large-scale magnetic fields. This is in stark contrast to the common idea that small-scale magnetic fields should be harmful to large-scale dynamo action. These dynamos occur in the presence of a large-scale velocity shear and do not require net helicity, resulting from off-diagonal components of the turbulent resistivity tensor as the magnetic analogue of the "shear-current" effect. Given the inevitable existence of nonhelical small-scale magnetic fields in turbulent plasmas, as well as the generic nature of velocity shear, the suggested mechanism may help explain the generation of large-scale magnetic fields across a wide range of astrophysical objects. PMID- 26551121 TI - Role of Ion Kinetic Physics in the Interaction of Magnetic Flux Ropes. AB - To explain many natural magnetized plasma phenomena, it is crucial to understand how rates of collisionless magnetic reconnection scale in large magnetohydrodynamic (MHD) scale systems. Simulations of isolated current sheets conclude such rates are independent of system size and can be reproduced by the Hall-MHD model, but neglect sheet formation and coupling to MHD scales. Here, it is shown for the problem of flux-rope merging, which includes this formation and coupling, that the Hall-MHD model fails to reproduce the kinetic results. The minimum sufficient model must retain ion kinetic effects, which set the ion diffusion region geometry and give time-averaged rates that reduce significantly with system size, leading to different global evolution in large systems. PMID- 26551122 TI - Dynamical Quasicondensation of Hard-Core Bosons at Finite Momenta. AB - Long-range order in quantum many-body systems is usually associated with equilibrium situations. Here, we experimentally investigate the quasicondensation of strongly interacting bosons at finite momenta in a far-from-equilibrium case. We prepare an inhomogeneous initial state consisting of one-dimensional Mott insulators in the center of otherwise empty one-dimensional chains in an optical lattice with a lattice constant d. After suddenly quenching the trapping potential to zero, we observe the onset of coherence in spontaneously forming quasicondensates in the lattice. Remarkably, the emerging phase order differs from the ground-state order and is characterized by peaks at finite momenta +/ (pi/2)(h/d) in the momentum distribution function. PMID- 26551123 TI - Atomic-Level Understanding of "Asymmetric Twins" in Boron Carbide. AB - Recent observations of planar defects in boron carbide have been shown to deviate from perfect mirror symmetry and are referred to as "asymmetric twins." Here, we demonstrate that these asymmetric twins are really phase boundaries that form in stoichiometric B(4)C (i.e., B(12)C(3)) but not in B(13)C(2). TEM observations and ab initio simulations have been coupled to show that these planar defects result from an interplay of stoichiometry, atomic positioning, icosahedral twinning, and structural hierarchy. The composition of icosahedra in B(4)C is B(11)C and translation of the carbon atom from a polar to equatorial site leads to a shift in bonding and a slight distortion of the lattice. No such distortion is observed in boron-rich B(13)C(2) because the icosahedra do not contain carbon. Implications for tailoring boron carbide with stoichiometry and extrapolations to other hierarchical crystalline materials are discussed. PMID- 26551124 TI - Elastic Waves Scattering without Conversion in Metamaterials with Simultaneous Zero Indices for Longitudinal and Transverse Waves. AB - We theoretically investigate elastic waves propagating in metamaterials with simultaneous zero indices for both the longitudinal and transverse waves. With scattering objects (here cylinders) present in the metamaterial slabs, while the elastic waves can mostly transmit through the metamaterial slabs perfectly, exhibiting the well-known cloaking effect of zero-index metamaterials, they nevertheless become totally blocked at resonances, indicating strong elastic wave scattering by the objects in the cases. However, despite the occurrence of the elastic wave scattering, there is, counterintuitively, no mode conversion between the longitudinal and transverse waves in the process, completely in contrast to that in conventional elastic media. A design of a two-dimensional phononic crystal with these peculiar properties is presented. PMID- 26551125 TI - X-Ray Photon Correlation Spectroscopy Reveals Intermittent Aging Dynamics in a Metallic Glass. AB - We use coherent x rays to probe the aging dynamics of a metallic glass directly on the atomic level. Contrary to the common assumption of a steady slowing down of the dynamics usually observed in macroscopic studies, we show that the structural relaxation processes underlying aging in this metallic glass are intermittent and highly heterogeneous at the atomic scale. Moreover, physical aging is triggered by cooperative atomic rearrangements, driven by the relaxation of internal stresses. The rich diversity of this behavior reflects a complex energy landscape, giving rise to a unique type of glassy-state dynamics. PMID- 26551126 TI - Electron Microscopy of Probability Currents at Atomic Resolution. AB - Atomic resolution transmission electron microscopy records the spatially resolved scattered electron density to infer positions, density, and species of atoms. These data are indispensable for studying the relation between structure and properties in solids. Here, we show how this signal can be augmented by the lateral probability current of the scattered electrons in the object plane at similar resolutions and fields of view. The currents are reconstructed from a series of three atomic resolution TEM images recorded under a slight difference of perpendicular line foci. The technique does not rely on the coherence of the electron beam and can be used to reveal electric, magnetic, and strain fields with incoherent electron beams as well as correlations in inelastic transitions, such as electron magnetic chiral dichroism. PMID- 26551127 TI - Frohlich Electron-Phonon Vertex from First Principles. AB - We develop a method for calculating the electron-phonon vertex in polar semiconductors and insulators from first principles. The present formalism generalizes the Frohlich vertex to the case of anisotropic materials and multiple phonon branches, and can be used either as a postprocessing correction to standard electron-phonon calculations, or in conjunction with ab initio interpolation based on maximally localized Wannier functions. We demonstrate this formalism by investigating the electron-phonon interactions in anatase TiO(2), and show that the polar vertex significantly reduces the electron lifetimes and enhances the anisotropy of the coupling. The present work enables ab initio calculations of carrier mobilities, lifetimes, mass enhancement, and pairing in polar materials. PMID- 26551128 TI - Collapse of the Mott Gap and Emergence of a Nodal Liquid in Lightly Doped Sr(2)IrO(4). AB - We report angle resolved photoemission experiments on the electron doped Heisenberg antiferromagnet (Sr(1-x)La(x))(2)IrO(4). For a doping level of x=0.05, we find an unusual metallic state with coherent nodal excitations and an antinodal pseudogap bearing strong similarities with underdoped cuprates. This state emerges from a rapid collapse of the Mott gap with doping resulting in a large underlying Fermi surface that is backfolded by a (pi,pi) reciprocal lattice vector which we attribute to the intrinsic structural distortion of Sr(2)IrO(4). PMID- 26551129 TI - Development of Path Integral Monte Carlo Simulations with Localized Nodal Surfaces for Second-Row Elements. AB - We extend the applicability range of fermionic path integral Monte Carlo simulations to heavier elements and lower temperatures by introducing various localized nodal surfaces. Hartree-Fock nodes yield the most accurate prediction for pressure and internal energy, which we combine with the results from density functional molecular dynamics simulations to obtain a consistent equation of state for hot, dense silicon under plasma conditions and in the regime of warm dense matter (2.3-18.6 g cm(-3), 5.0*10(5)-1.3*10(8) K). The shock Hugoniot curve is derived and the structure of the fluid is characterized with various pair correlation functions. PMID- 26551130 TI - Magnetoinfrared Spectroscopy of Landau Levels and Zeeman Splitting of Three Dimensional Massless Dirac Fermions in ZrTe(5). AB - We present a magnetoinfrared spectroscopy study on a newly identified three dimensional (3D) Dirac semimetal ZrTe(5). We observe clear transitions between Landau levels and their further splitting under a magnetic field. Both the sequence of transitions and their field dependence follow quantitatively the relation expected for 3D massless Dirac fermions. The measurement also reveals an exceptionally low magnetic field needed to drive the compound into its quantum limit, demonstrating that ZrTe(5) is an extremely clean system and ideal platform for studying 3D Dirac fermions. The splitting of the Landau levels provides direct, bulk spectroscopic evidence that a relatively weak magnetic field can produce a sizable Zeeman effect on the 3D Dirac fermions, which lifts the spin degeneracy of Landau levels. Our analysis indicates that the compound evolves from a Dirac semimetal into a topological line-node semimetal under the current magnetic field configuration. PMID- 26551131 TI - Detecting Band Inversions by Measuring the Environment: Fingerprints of Electronic Band Topology in Bulk Phonon Linewidths. AB - The interplay between topological phases of matter and dissipative baths constitutes an emergent research topic with links to condensed matter, photonic crystals, cold atomic gases, and quantum information. While recent studies suggest that dissipative baths can induce topological phases in intrinsically trivial quantum materials, the backaction of topological invariants on dissipative baths is overlooked. By exploring this backaction for a centrosymmetric Dirac insulator coupled to phonons, we show that the linewidths of bulk optical phonons can reveal electronic band inversions. This result is the first known example where topological phases of an open quantum system may be detected by measuring the bulk properties of the surrounding environment. PMID- 26551132 TI - Interplay of Electron and Nuclear Spin Noise in n-Type GaAs. AB - We present spin-noise spectroscopy measurements on an ensemble of donor-bound electrons in ultrapure GaAs:Si covering temporal dynamics over 6 orders of magnitude from milliseconds to nanoseconds. The spin-noise spectra detected at the donor-bound exciton transition show the multifaceted dynamical regime of the ubiquitous mutual electron and nuclear spin interaction typical for III-V-based semiconductor systems. The experiment distinctly reveals the finite Overhauser shift of an electron spin precession at zero external magnetic field and a second contribution around zero frequency stemming from the electron spin components parallel to the nuclear spin fluctuations. Moreover, at very low frequencies, features related with time-dependent nuclear spin fluctuations are clearly resolved making it possible to study the intricate nuclear spin dynamics at zero and low magnetic fields. The findings are in agreement with the developed model of electron and nuclear spin noise. PMID- 26551133 TI - Intrinsic Transparent Conductors without Doping. AB - Transparent conductors (TCs) combine the usually contraindicated properties of electrical conductivity with optical transparency and are generally made by starting with a transparent insulator and making it conductive via heavy doping, an approach that generally faces severe "doping bottlenecks." We propose a different idea for TC design-starting with a metallic conductor and designing transparency by control of intrinsic interband transitions and intraband plasmonic frequency. We identify the specific design principles for three such prototypical intrinsic TC classes and then search computationally for materials that satisfy them. Remarkably, one of the intrinsic TC, Ag(3)Al(22)O(34), is predicted also to be a prototype 3D compounds that manifest natural 2D electron gas regions with very high electron density and conductivity. PMID- 26551134 TI - Nonanalyticity, Valley Quantum Phases, and Lightlike Exciton Dispersion in Monolayer Transition Metal Dichalcogenides: Theory and First-Principles Calculations. AB - Exciton dispersion as a function of center-of-mass momentum Q is essential to the understanding of exciton dynamics. We use the ab initio GW-Bethe-Salpeter equation method to calculate the dispersion of excitons in monolayer MoS(2) and find a nonanalytic lightlike dispersion. This behavior arises from an unusual |Q| term in both the intra- and intervalley exchange of the electron-hole interaction, which concurrently gives rise to a valley quantum phase of winding number two. A simple effective Hamiltonian to Q(2) order with analytic solutions is derived to describe quantitatively these behaviors. PMID- 26551135 TI - Exchange-Induced Spin Blockade in a Two-Electron Double Quantum Dot. AB - We have experimentally identified the exchange-induced spin blockade in a GaAs double quantum dot. The transport is suppressed only when the eigenstates are well-defined singlet and triplet states, and thus sensitive to dynamic nuclear spin polarization that causes singlet-triplet mixing. This gives rise to unusual current spectra, such as a sharp current dip and an asymmetric current profile near the triplet resonance of a double quantum dot. Numerical simulations suggest that the current dip is a signature of identical nuclear-spin polarization in the two dots, which is attractive for coherent spin manipulations in a material with nuclear spins. PMID- 26551136 TI - Evolution of Density of States and a Spin-Resolved Checkerboard-Type Pattern Associated with the Majorana Bound State. AB - In terms of the Bogoliubov-de Gennes approach, we investigate the Majorana bound state (MBS) in a vortex of proximity-induced superconductivity on the surface of a topological insulator. Mapping out the local density of states (LDOS) of quasiparticle excitations as a function of energy and distance from the vortex center, it is found that the spectral distribution evolves from a V shape to a Y shape with the emergence of a MBS upon variation of the chemical potential, consistent with the STM/STS measurement in a very recent experiment [Xu et al., Phys. Rev. Lett. 114, 017001 (2015)] on a Bi(2)Te(3) thin layer on the top of NbSe(2). Moreover, we demonstrate that there is a checkerboard-type pattern in the relative LDOS between the spin-up and -down channels, where the quantum mechanical wave function of the MBS manifests itself clearly as a single quantum state. Therefore, a spin-resolved STM/STS technique is expected to be able to provide phase-sensitive evidence for a MBS in the vortex core of a topological superconductor. PMID- 26551137 TI - Emergent Power-Law Phase in the 2D Heisenberg Windmill Antiferromagnet: A Computational Experiment. AB - In an extensive computational experiment, we test Polyakov's conjecture that under certain circumstances an isotropic Heisenberg model can develop algebraic spin correlations. We demonstrate the emergence of a multispin U(1) order parameter in a Heisenberg antiferromagnet on interpenetrating honeycomb and triangular lattices. The correlations of this relative phase angle are observed to decay algebraically at intermediate temperatures in an extended critical phase. Using finite-size scaling we show that both phase transitions are of the Berezinskii-Kosterlitz-Thouless type, and at lower temperatures we find long range Z(6) order. PMID- 26551138 TI - Elastic Gauge Fields in Weyl Semimetals. AB - We show that, as happens in graphene, elastic deformations couple to the electronic degrees of freedom as pseudogauge fields in Weyl semimetals. We derive the form of the elastic gauge fields in a tight-binding model hosting Weyl nodes and see that this vector electron-phonon coupling is chiral, providing an example of axial gauge fields in three dimensions. As an example of the new response functions that arise associated with these elastic gauge fields, we derive a nonzero phonon Hall viscosity for the neutral system at zero temperature. The axial nature of the fields provides a test of the chiral anomaly in high energy with three axial vector couplings. PMID- 26551139 TI - Solitonic Spin-Liquid State Due to the Violation of the Lifshitz Condition in Fe(1+y)Te. AB - A combination of phenomenological analysis and Mossbauer spectroscopy experiments on the tetragonal Fe(1+y)Te system indicates that the magnetic ordering transition in compounds with higher Fe excess, y>=0.11, is unconventional. Experimentally, a liquidlike magnetic precursor with quasistatic spin order is found from significantly broadened Mossbauer spectra at temperatures above the antiferromagnetic transition. The incommensurate spin-density wave order in Fe(1+y)Te is described by a magnetic free energy that violates the weak Lifshitz condition in the Landau theory of second-order transitions. The presence of multiple Lifshitz invariants provides the mechanism to create multidimensional, twisted, and modulated solitonic phases. PMID- 26551140 TI - Topological Characterization of Extended Quantum Ising Models. AB - We show that a class of exactly solvable quantum Ising models, including the transverse-field Ising model and anisotropic XY model, can be characterized as the loops in a two-dimensional auxiliary space. The transverse-field Ising model corresponds to a circle and the XY model corresponds to an ellipse, while other models yield cardioid, limacon, hypocycloid, and Lissajous curves etc. It is shown that the variation of the ground state energy density, which is a function of the loop, experiences a nonanalytical point when the winding number of the corresponding loop changes. The winding number can serve as a topological quantum number of the quantum phases in the extended quantum Ising model, which sheds some light upon the relation between quantum phase transition and the geometrical order parameter characterizing the phase diagram. PMID- 26551141 TI - Spin-Peierls Instability of Three-Dimensional Spin Liquids with Majorana Fermi Surfaces. AB - Three-dimensional (3D) variants of the Kitaev model can harbor gapless spin liquids with a Majorana Fermi surface on certain tricoordinated lattice structures such as the recently introduced hyperoctagon lattice. Here, we investigate Fermi surface instabilities arising from additional spin exchange terms (such as a Heisenberg coupling) which introduce interactions between the emergent Majorana fermion degrees of freedom. We show that independent of the sign and structure of the interactions, the Majorana surface is always unstable. Generically, the system spontaneously doubles its unit cell at exponentially small temperatures and forms a spin liquid with line nodes. Depending on the microscopics, further symmetries of the system can be broken at this transition. These spin-Peierls instabilities of a 3D spin liquid are closely related to BCS instabilities of fermions. PMID- 26551142 TI - Stochastic Approach to Phonon-Assisted Optical Absorption. AB - We develop a first-principles theory of phonon-assisted optical absorption in semiconductors and insulators which incorporates the temperature dependence of the electronic structure. We show that the Hall-Bardeen-Blatt theory of indirect optical absorption and the Allen-Heine theory of temperature-dependent band structures can be derived from the present formalism by retaining only one-phonon processes. We demonstrate this method by calculating the optical absorption coefficient of silicon using an importance sampling Monte Carlo scheme, and we obtain temperature-dependent line shapes and band gaps in good agreement with experiment. The present approach opens the way to predictive calculations of the optical properties of solids at finite temperature. PMID- 26551143 TI - Experimental Demonstration of Effective Medium Approximation Breakdown in Deeply Subwavelength All-Dielectric Multilayers. AB - We report the first experimental demonstration of anomalous breakdown of the effective medium approximation in all-dielectric deeply subwavelength thickness (d~lambda/160-lambda/30) multilayers, as recently predicted theoretically [H. H. Sheinfux et al., Phys. Rev. Lett. 113, 243901 (2014)]. Multilayer stacks are composed of alternating alumina and titania layers fabricated using atomic layer deposition. For light incident on such multilayers at angles near the total internal reflection, we observe pronounced differences in the reflectance spectra for structures with 10- vs 20-nm thick layers, as well as for structures with different layers ordering, contrary to the predictions of the effective medium approximation. The reflectance difference can reach values up to 0.5, owing to the chosen geometrical configuration with an additional resonator layer employed for the enhancement of the effect. Our results are important for the development of new high-precision multilayer ellipsometry methods and schemes, as well as in a broad range of sensing applications. PMID- 26551144 TI - Comment on "Decrease of Atmospheric Neutron Counts Observed during Thunderstorms". PMID- 26551145 TI - Alekseenko et al. Reply. PMID- 26551146 TI - Erratum: Direct Measurement of the (23)Na(alpha,p)(26)Mg Reaction Cross Section at Energies Relevant for the Production of Galactic (26)Al [Phys. Rev. Lett. 112, 152701 (2014)]. PMID- 26551147 TI - Single-domain antibodies for biomedical applications. AB - Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development. PMID- 26551149 TI - Gold nanoparticles induce apoptosis, endoplasmic reticulum stress events and cleavage of cytoskeletal proteins in human neutrophils. AB - Gold nanoparticles (AuNPs) are promising candidates for developing nanomedicines, for the treatment of different disorders, including inflammatory diseases. However, how AuNPs could alter the biology of human neutrophils, key player cells in inflammation, is a poorly documented area of research. Here we found that, although AuNP of 20 nm (AuNP20) could be internalized in cytosolic vacuoles but that AuNP70 were localized at the cell membrane, both induced apoptosis similarly by a caspase-dependent mechanism. AuNPs induced degradation of the cytoskeletal proteins vimentin, lamin B1 and gelsolin, but, unexpectedly, did not increase their cell surface expression. Consequent with caspase-4 processing, AuNPs were found to activate endoplasmic reticulum (ER)-stress, as evidenced by activation of the three ER sensors, IRE1 (inositol-requiring protein-1), ATF-6 (activating transcription factor-6) and PERK (protein kinase RNA (PKR)-like ER kinase). AuNPs are novel human neutrophil proapoptotic agents indicating that they are toxic to these cells. However, the fact that they do not induce cell surface expression of cytoskeletal proteins could decrease potential adverse effects and toxicity of AuNPs by limiting, for example, the production of autoantibody against cytoskeleton components. PMID- 26551148 TI - Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in the etiology of renal cell carcinoma. AB - BACKGROUND: Meat-cooking mutagens may be associated with renal cell carcinoma (RCC) risk. In the current study, the authors examined associations between meat cooking mutagens, genetic susceptibility variants, and risk of RCC. METHODS: The authors used 659 newly diagnosed RCC cases and 699 healthy controls to investigate the association between dietary intake of meat-cooking mutagens and RCC. They examined whether associations varied by risk factors for RCC and genetic susceptibility variants previously identified from genome-wide association studies. Odds ratios and 95% confidence intervals were estimated using tertiles of intake of dietary polycyclic aromatic hydrocarbons/heterocyclic amines. RESULTS: Dietary intake of the mutagenic compounds 2-amino-3,8 dimethylimidazo-(4,5-f) quinoxaline (MeIQx) and 2-amino-1 methyl-6 phenylimidazo(4,5-b)pyridine (PhIP) were found to be significantly associated with an increased risk of RCC (odds ratios across tertiles: 1.00 [referent], 1.28 [95% confidence interval, 0.94-1.74], and 1.95 [95% confidence interval, 1.43 2.66] [P for trend <.001], respectively; and 1.00 [referent], 1.41 [95% confidence interval, 1.04-1.90], and 1.54 [95% confidence interval, 1.14-2.07] [P for trend =.02], respectively). The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5 trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06). CONCLUSIONS: The intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions. PMID- 26551150 TI - Identification of TIM-3 as a Leukemic Stem Cell Surface Molecule in Primary Acute Myeloid Leukemia. AB - Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target in AML. Eradication of LSCs should be a critical and efficient therapeutic approach for the cure of AML. T-cell immunoglobulin mucin-3 (TIM-3) is expressed in most types of AML LSCs, but not in normal hematopoietic stem cells (HSCs); therefore, TIM-3 would be one of the promising therapeutic targets to specifically kill AML LSCs, sparing normal HSCs. In xenograft models reconstituted with human AML LSCs or human normal HSCs, an anti-human TIM-3 mouse antibody with cytotoxic activities exerts a potent anti leukemic effect by targeting AML LSCs but does not affect normal human hematopoiesis in vivo. Here, we would like to introduce the recent studies on TIM 3 in normal and malignant hematopoiesis. PMID- 26551151 TI - Variability in group size and the evolution of collective action. AB - Models of the evolution of collective action typically assume that interactions occur in groups of identical size. In contrast, social interactions between animals occur in groups of widely dispersed size. This paper models collective action problems as two-strategy multiplayer games and studies the effect of variability in group size on the evolution of cooperative behavior under the replicator dynamics. The analysis identifies elementary conditions on the payoff structure of the game implying that the evolution of cooperative behavior is promoted or inhibited when the group size experienced by a focal player is more or less variable. Similar but more stringent conditions are applicable when the confounding effect of size-biased sampling, which causes the group-size distribution experienced by a focal player to differ from the statistical distribution of group sizes, is taken into account. PMID- 26551152 TI - A non-linear mathematical model for a three species ecosystem: Hippos in Lake Edward. AB - In this work we study a non-linear mathematical model based on three different interacting species. We apply our model to Lake Edward ecosystem consisting in hippos, tilapia fishes and human inhabitants. In this case, we estimate the values of the key parameters using actual data and show the reliability of the proposed model as a predictive tool. We also show, via numerical calculations and parameter values that the ecosystem associated to the lake is very far from reaching a stable equilibrium. Through our analysis we provide the conditions for a possible coexistence among the three species. PMID- 26551153 TI - Emergent behaviour in a chlorophenol-mineralising three-tiered microbial 'food web'. AB - Anaerobic digestion enables the water industry to treat wastewater as a resource for generating energy and recovering valuable by-products. The complexity of the anaerobic digestion process has motivated the development of complex models. However, this complexity makes it intractable to pin-point stability and emergent behaviour. Here, the widely used Anaerobic Digestion Model No. 1 (ADM1) has been reduced to its very backbone, a syntrophic two-tiered microbial 'food chain' and a slightly more complex three-tiered microbial 'food web', with their stability analysed as a function of the inflowing substrate concentration and dilution rate. Parameterised for phenol and chlorophenol degradation, steady-states were always stable and non-oscillatory. Low input concentrations of chlorophenol were sufficient to maintain chlorophenol- and phenol-degrading populations but resulted in poor conversion and a hydrogen flux that was too low to sustain hydrogenotrophic methanogens. The addition of hydrogen and phenol boosted the populations of all three organisms, resulting in the counterintuitive phenomena that (i) the phenol degraders were stimulated by adding hydrogen, even though hydrogen inhibits phenol degradation, and (ii) the dechlorinators indirectly benefitted from measures that stimulated their hydrogenotrophic competitors; both phenomena hint at emergent behaviour. PMID- 26551154 TI - The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes. AB - The anti-tumour and pro-tumour roles of Th1/Th2 immune cells and M1/M2 macrophages have been documented by numerous experimental studies. However, it is still unknown how these immune cells interact with each other to control tumour dynamics. Here, we use a mathematical model for the interactions between mouse melanoma cells, Th2/Th1 cells and M2/M1 macrophages, to investigate the unknown role of the re-polarisation between M1 and M2 macrophages on tumour growth. The results show that tumour growth is associated with a type-II immune response described by large numbers of Th2 and M2 cells. Moreover, we show that (i) the ratio k of the transition rates k12 (for the re-polarisation M1->M2) and k21 (for the re-polarisation M2->M1) is important in reducing tumour population, and (ii) the particular values of these transition rates control the delay in tumour growth and the final tumour size. We also perform a sensitivity analysis to investigate the effect of various model parameters on changes in the tumour cell population, and confirm that the ratio k alone and the ratio of M2 and M1 macrophage populations at earlier times (e.g., day 7) cannot always predict the final tumour size. PMID- 26551155 TI - Algorithmic height compression of unordered trees. AB - By nature, tree structures frequently present similarities between their sub parts. Making use of this redundancy, different types of tree compression techniques have been designed in the literature to reduce the complexity of tree structures. A popular and efficient way to compress a tree consists of merging its isomorphic subtrees, which produces a directed acyclic graph (DAG) equivalent to the original tree. An important property of this method is that the compressed structure (i.e. the DAG) has the same height as the original tree, thus limiting partially the possibility of compression. In this paper we address the problem of further compressing this DAG in height. The difficulty is that compression must be carried out on substructures that are not exactly isomorphic as they are strictly nested within each-other. We thus introduced a notion of quasi isomorphism between subtrees that makes it possible to define similar patterns along any given path in a tree. We then proposed an algorithm to detect these patterns and to merge them, thus leading to compressed structures corresponding to DAGs augmented with return edges. In this way, redundant information is removed from the original tree in both width and height, thus achieving minimal structural compression. The complete compression algorithm is then illustrated on the compression of various plant-like structures. PMID- 26551156 TI - Mathematical modeling of drug resistance due to KRAS mutation in colorectal cancer. AB - The most challenging task in colorectal cancer research nowadays is to understand the development of acquired resistance to anti-EGFR drugs. The key reason for this problem is the KRAS mutations appearance after the treatment with monoclonal antibodies (moAb). Here we present a mathematical model for the analysis of KRAS mutations behavior in colorectal cancer with respect to moAb treatments. To evaluate the drug performance we have developed equations for two types of tumors cells, KRAS mutated and KRAS wild-type. Both tumor cell populations were treated with a combination of moAb and chemotherapy drugs. It was observed that even the minimal initial concentration of KRAS mutation before the treatment has the ability to make the tumor refractory to the treatment. Minor population of KRAS mutations has strong influence on large number of wild-type cells as well rendering them resistant to chemotherapy. Patient's immune responses are specifically taken into considerations and it is found that, in case of KRAS mutations, the immune strength does not affect medication efficacy. Finally, cetuximab (moAb) and irinotecan (chemotherapy) drugs are analyzed as first-line treatment of colorectal cancer with few KRAS mutated cells. Results show that this combined treatment could be only effective for patients with high immune strengths and it should not be recommended as first-line therapy for patients with moderate immune strengths or weak immune systems because of a potential risk of relapse, with KRAS mutant cells acquired resistance involved with them. PMID- 26551157 TI - Quantifying morphological features of actin cytoskeletal filaments in plant cells based on mathematical morphology. AB - By quantifying the morphological properties of biological structures, we can better evaluate complex shapes and detect subtle morphological changes in organisms. In this paper, we propose a shape analysis method based on morphological image processing, and apply it to image analysis of actin cytoskeletal filaments in root hair cells of Arabidopsis thaliana. In plant cells, the actin cytoskeletal filaments have critical roles in various cellular processes such as vesicle trafficking and organelle motility. The dynamics of vesicles and organelles in plant cells depend on actin cytoskeletal filaments, regulating cell division and cell enlargement. To better understand the actin dependent organelle motility, we attempted to quantify the organization of actin filaments in the root hair cells of the root hair defective 3 (rhd3) mutant. RHD3 is involved in actin organization, and its defect has been reported to affect the dynamics of various vesicles and organelles. We measured three shape features of the actin filaments in wild-type and mutant plants. One feature (thickness) was depicted on a grayscale; the others (describing the complexity of the filament network patterns in two-dimensional space) were depicted as binary features. The morphological phenotypes of the cytoskeletal filaments clearly differed between wild-type and mutant. Subtle variations of filament morphology among the mutants were detected and statistically quantified. PMID- 26551158 TI - Noisy predator-prey model explains oscillation patterns in sockeye salmon data. AB - A model of sockeye salmon population dynamics that incorporates predator-prey dynamics in the nursery lakes, salmon migration and stochastic effects is compared to Fraser River sockeye salmon spawner numbers with respect to cyclic dominance. For this comparison we use a method developed by White et al. (2014) to calculate measures for the consistency and strength of cyclic dominance in the time series using its wavelet transform. We find that the model can match the oscillation patterns found in nature, both for persistently oscillating populations and for intermittent oscillations. It matches persistently oscillating populations much better than a model that does not incorporate predator-prey interaction. Persistent oscillations are more likely to occur in the model if the growth conditions for the sockeye fry are good and the coupling to the predator is strong. PMID- 26551159 TI - Time-delayed model of immune response in plants. AB - In the studies of plant infections, the plant immune response is known to play an essential role. In this paper we derive and analyse a new mathematical model of plant immune response with particular account for post-transcriptional gene silencing (PTGS). Besides biologically accurate representation of the PTGS dynamics, the model explicitly includes two time delays to represent the maturation time of the growing plant tissue and the non-instantaneous nature of the PTGS. Through analytical and numerical analysis of stability of the steady states of the model we identify parameter regions associated with recovery and resistant phenotypes, as well as possible chronic infections. Dynamics of the system in these regimes is illustrated by numerical simulations of the model. PMID- 26551160 TI - Understanding PGE2, LXA4 and LTB4 balance during Mycobacterium tuberculosis infection through mathematical model. AB - Infection of humans with Mycobacterium tuberculosis (Mtb) results in diverse outcomes that range from acute disease to establishment of persistence and to even clearance of the pathogen. These different outcomes represent the combined result of host heterogeneity on the one hand, and virulence properties of the infecting strain of pathogen on the other. From the standpoint of the host, the balance between PGE2, LXA4 and LTB4 represents at least one of the factors that dictates the eventual pathophysiology. We therefore built an ODE model to describe the host-pathogen interaction and studied the local stability properties of the system, to obtain the parametric conditions that lead to different disease outcomes. We then modulated levels of the pro- and anti-inflammatory lipid mediators to better understand the convergence between host phenotype and factors that relate to virulence properties of the pathogen. Global sensitivity analysis, using the variance-based method of extended Fourier Amplitude Sensitivity Test (eFAST), revealed that disease severity was indeed defined by combined effects of phenotypic variability at the level of both host and pathogen. Interestingly here, [PGE2] was found to act as a switch between bacterial clearance and acute disease. Our mathematical model suggests that development of more effective treatments for tuberculosis will be contingent upon a better understanding of how the intrinsic variability at the level of both host and pathogen contribute to influence the nature of interactions between these two entities. PMID- 26551161 TI - Biomimetically Ornamented Rapid Prototyping Fabrication of an Apatite-Collagen Polycaprolactone Composite Construct with Nano-Micro-Macro Hierarchical Structure for Large Bone Defect Treatment. AB - Biomaterial-based bone graft substitute with favorable mechanical and biological properties could be used as an alternative to autograft for large defect treatment. Here, an apatite-collagen-polycaprolactone (Ap-Col-PCL) composite construct was developed with unique nano-micro-macro hierarchical architectures by combining rapid prototyping (RP) fabrication technology and a 3D functionalization strategy. Macroporous PCL framework was fabricated using RP technology, then functionalized by collagen incorporation and biomimetic deposition. Ap-Col-PCL composite construct was characterized with hierarchical architectures of a nanoscale (~100 nm thickness and ~1 MUm length) platelike apatite coating on the microporous (126 +/- 18 MUm) collagen networks, which homogeneously filled the macroporous (~1000 MUm) PCL frameworks and possessed a favorable hydrophilic property and compressive modulus (68.75 +/- 3.39 MPa) similar to that of cancellous bone. Moreover, in vitro cell culture assay and in vivo critical-sized bone defect implantation demonstrated that the Ap-Col-PCL construct could not only significantly increase the cell adhesion capability (2.0 fold) and promote faster cell proliferation but also successfully bridge the segmental long bone defect within 12 weeks with much more bone regeneration (5.2 fold), better osteointegration (7.2-fold), and a faster new bone deposition rate (2.9-fold). Our study demonstrated that biomimetically ornamented Ap-Col-PCL constructs exhibit a favorable mechanical property, more bone tissue ingrowth, and better osteointegration capability as an effective bone graft substitute for critical-sized bone defect treatment; meanwhile, it can also harness the advantages of RP technology, in particular, facilitating the customization of the shape and size of implants according to medical images during clinical application. PMID- 26551162 TI - Functionalized Nanofiber Meshes Enhance Immunosorbent Assays. AB - Three-dimensional substrates with high surface-to-volume ratios and subsequently large protein binding capacities are of interest for advanced immunosorbent assays utilizing integrated microfluidics and nanosensing elements. A library of bioactive and antifouling electrospun nanofiber substrates, which are composed of high-molecular-weight poly(oxanorbornene) derivatives, is described. Specifically, a set of copolymers are synthesized from three 7-oxanorbornene monomers to create a set of water insoluble copolymers with both biotin (bioactive) and triethylene glycol (TEG) (antifouling) functionality. Porous three-dimensional nanofiber meshes are electrospun from these copolymers with the ability to specifically bind streptavidin while minimizing the nonspecific binding of other proteins. Fluorescently labeled streptavidin is used to quantify the streptavidin binding capacity of each mesh type through confocal microscopy. A simplified enzyme-linked immunosorbent assay (ELISA) is presented to assess the protein binding capabilities and detection limits of these nanofiber meshes under both static conditions (26 h) and flow conditions (1 h) for a model target protein (i.e., mouse IgG) using a horseradish peroxidase (HRP) colorimetric assay. Bioactive and antifouling nanofiber meshes outperform traditional streptavidin-coated polystyrene plates under flow, validating their use in future advanced immunosorbent assays and their compatibility with microfluidic-based biosensors. PMID- 26551164 TI - Yb(OTf)3-Mediated Access to Furans from beta-Ketothioamides via Eschenmoser Sulfide Contraction Reaction. AB - A mild and straightforward synthetic protocol for construction of a furan skeleton promoted by Yb(OTf)3 from beta-ketothioamides and arylglyoxals has been developed at room temperature. Importantly, this protocol involves a tandem sequence that includes aldol condensation, N-cyclization, ring opening, O cyclization, S-cyclization, and Eschenmoser sulfide contraction. PMID- 26551163 TI - Appropriate Use Criteria for Coronary Revascularization and Trends in Utilization, Patient Selection, and Appropriateness of Percutaneous Coronary Intervention. AB - IMPORTANCE: Appropriate Use Criteria for Coronary Revascularization were developed to critically evaluate and improve patient selection for percutaneous coronary intervention (PCI). National trends in the appropriateness of PCI have not been examined. OBJECTIVE: To examine trends in PCI utilization, patient selection, and procedural appropriateness following the introduction of Appropriate Use Criteria. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, longitudinal, cross-sectional analysis of patients undergoing PCI between July 1, 2009, and December 31, 2014, at hospitals continuously participating in the National Cardiovascular Data Registry CathPCI registry over the study period. MAIN OUTCOMES AND MEASURES: Proportion of nonacute PCIs classified as inappropriate at the patient and hospital level using the 2012 Appropriate Use Criteria for Coronary Revascularization. RESULTS: A total of 2.7 million PCI procedures from 766 hospitals were included. Annual PCI volume of acute indications was consistent over the study period (377,540 in 2010; 374,543 in 2014), but the volume of nonacute PCIs decreased from 89,704 in 2010 to 59,375 in 2014. Among patients undergoing nonacute PCI, there were significant increases in angina severity (Canadian Cardiovascular Society grade III/IV angina, 15.8% in 2010 and 38.4% in 2014), use of antianginal medications prior to PCI (at least 2 antianginal medications, 22.3% in 2010 and 35.1% in 2014), and high-risk findings on noninvasive testing (22.2% in 2010 and 33.2% in 2014) (P < .001 for all), but only modest increases in multivessel coronary artery disease (43.7% in 2010 and 47.5% in 2014, P < .001). The proportion of nonacute PCIs classified as inappropriate decreased from 26.2% (95% CI, 25.8%-26.6%) to 13.3% (95% CI, 13.1% 13.6%), and the absolute number of inappropriate PCIs decreased from 21,781 to 7921. Hospital-level variation in the proportion of PCIs classified as inappropriate persisted over the study period (median, 12.6% [interquartile range, 5.9%-22.9%] in 2014). CONCLUSIONS AND RELEVANCE: Since the publication of the Appropriate Use Criteria for Coronary Revascularization in 2009, there have been significant reductions in the volume of nonacute PCI. The proportion of nonacute PCIs classified as inappropriate has declined, although hospital-level variation in inappropriate PCI persists. PMID- 26551165 TI - Structural Dynamics of the Potassium Channel Blocker ShK: SRLS Analysis of (15)N Relaxation. AB - The 35-residue ShK peptide binds with high affinity to voltage-gated potassium channels. The dynamics of the binding surface was studied recently with (microsecond to millisecond) (15)N relaxation dispersion and (picosecond to nanosecond) (15)N spin relaxation of the N-H bonds. Relaxation dispersion revealed microsecond conformational-exchange-mediated exposure of the functionally important Y23 side chain to the peptide surface. The spin relaxation parameters acquired at 14.1 and 16.45 T have been subjected to model-free (MF) analysis, which yielded a squared generalized order parameter, S(2), of approximately 0.85 for virtually all of the N-H bonds. Only a "rigid backbone" evaluation could be inferred. We ascribe this limited information to the simplicity of MF in the context of challenging data. To improve the analysis, we apply the slowly relaxing local structure (SRLS) approach, which is a generalization of MF. SRLS describes N-H bond dynamics in ShK in terms of a local potential, u, ranging from 10 to 18.5 kBT, and a local diffusion rate, D2, ranging from 4.2 * 10(8) to 2.4 * 10(10) s(-1). This analysis shows that u is outstandingly strong for Y23 and relatively weak for K22, whereas D2 is slow for Y23 and fast for K22. These observations are relevant functionally because of the key role of the K22-Y23 dyad in ShK binding to potassium channels. The disulfide bond network exhibits a medium-strength potential and an alternating wave-like D2 pattern. This is indicative of moderate structural restraints and motional plasticity, in support of, although not directly correlated with, the microsecond binding-related conformational exchange process detected previously. Thus, new information on functionally important residues in ShK and its overall conformational stability emerged from the SRLS analysis, as compared with the previous MF-based estimate of backbone dynamics as backbone rigidity. PMID- 26551166 TI - The Certified Midwife Credential and the Case for National Implementation. PMID- 26551167 TI - [Theoretical basis and clinical benefits of dry salt inhalation therapy]. AB - Dry salt inhalation (halotherapy) reproduces the microclimate of salt caves, with beneficial effect on health. Sodium chloride crystals are disrupted into very small particles (with a diameter less than 3 um), and this powder is artificially exhaled into the air of a comfortable room (its temperature is between 20-22 degrees C, and the relative humidity is low). The end-concentration of the salt in the air of the room will be between 10-30 mg/m(3). The sick (or healthy) persons spend 30-60 minutes in this room, usually 10-20 times. Due to the greater osmotic pressure the inhaled salt diminishes the oedema of the bronchial mucosa, decreases its inflammation, dissolves the mucus, and makes expectoration easier and faster (expectoration of air pollution and allergens will be faster, too). It inhibits the growth of bacteria and, in some case, kills them. Phagocyte activity is also increased. It has beneficial effect on the well being of the patients, and a relaxation effect on the central nervous system. It can prevent, or at least decrease the frequency of the respiratory tract inflammations. It produces better lung function parameters, diminishes bronchial hyperreactivity, which is the sign of decreasing inflammation. Its beneficial effect is true not only in inflammation of the lower respiratory tract, but also in acute or chronic upper airways inflammations. According to the international literature it has beneficial effect for some chronic dermatological disease, too, such as psoriasis, pyoderma and atopic dermatitis. This treatment (called as Indiso) is available under medical control in Hungary, too. PMID- 26551168 TI - [Recent advances in the treatment of antineutrophil cytoplasm antibody associated vasculitides]. AB - The authors review the nomenclature of vasculitides and the classification of antineutrophil cytoplasm antibody associated vasculitides and present the method of measuring disease activity (Five-factor Score, Birmingham Vasculitis Activity Score) and its role in defining therapeutical needs. They discuss the treatment algorithm of antineutrophil cytoplasm antibody associated vasculitides, present the sometimes equipotential medications used during the induction therapy followed by a maintenance regimen, and outline their usage and possible side effects that may require medical attention. They point out the importance of plasmapheresis as an adjunctive treatment in some cases, as well as indications and possible outcome of kidney transplantation in therapy-resistant cases. Finally, they review several ongoing clinical studies, as their outcome will probably influence therapeutical opportunities of antineutrophil cytoplasm antibody associated vasculitides in the next few years. PMID- 26551169 TI - [On-site fine-needle aspiration cytology of thyroid nodules. Quality assurance of the Bethesda System for Reporting Thyroid Cytopathology (2008)]. AB - INTRODUCTION: The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. AIM: The aim of this study was to determine the quality assurance of fine needle aspiration cytology of thyroid nodules. METHOD: Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 1384 patient with thyroid nodule underwent fine needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. CONCLUSION: The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values. PMID- 26551170 TI - [Abstracts of the invited and announced lectures to be presented at the 2015 Annual Congress of the Hungarian Society of Clinical Nutrition. Matrahaza, October 15-17, 2015]. PMID- 26551172 TI - Preterm Breech Presentation: A Comparison of Intended Vaginal and Intended Cesarean Delivery. AB - OBJECTIVE: To study the association of the intended mode of delivery and perinatal morbidity and mortality among breech fetuses who are delivered preterm. METHODS: We conducted a nationwide cohort study of women with a singleton pregnancy in breech presentation who delivered preterm (26 0/7-36 6/7 weeks of gestation) in the years 2000-2011. We compared perinatal outcomes according to the intended and actual mode of delivery using multivariate logistic regression analysis. We performed subgroup analyses of gestational age and parity. RESULTS: We studied 8,356 women with a preterm singleton breech delivery. Intended cesarean delivery (n=1,935) was not associated with a significant reduction in perinatal mortality compared with intended vaginal delivery (n=6,421) (1.3% compared with 1.5%; adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.60-1.57). However, the composite of perinatal mortality and morbidity was significantly reduced in the intended cesarean delivery group (8.7% compared with 10.4%; adjusted OR 0.77, 95% CI 0.63-0.93). In the subgroup of women delivering at 28-32 weeks of gestation, intended cesarean delivery was associated with a 1.7% risk of perinatal mortality compared with 4.1% with intended vaginal delivery (adjusted OR 0.27, 95% CI 0.10-0.77) and significantly reduced composite mortality and severe morbidity, 5.9% compared with 10.1% (adjusted OR 0.37, 95% CI 0.20-0.68). CONCLUSION: In women delivering a preterm breech fetus, cesarean delivery is associated with reduced perinatal mortality and morbidity. LEVEL OF EVIDENCE: II. PMID- 26551173 TI - Urinary Tract Injury at Benign Gynecologic Surgery and the Role of Cystoscopy: A Systematic Review and Meta-analysis. AB - OBJECTIVE: To calculate the rates of urinary tract injury detected during and after benign gynecologic surgery. To explore the role of routine intraoperative cystoscopy and determine if it helps in reducing injuries detected postoperatively. DATA SOURCES: We conducted a literature search for urinary tract injuries at benign gynecologic surgery in PubMed, EMBASE, ClinicalTrials.gov, and Web of Science from January 2004 to August 2014. We combined our results with a database from a previously published systematic review to include earlier studies. METHODS OF STUDY SELECTION: A total of 79 studies met our inclusion criteria. Excluded were letters to the editor, studies involving only selective cystoscopy in higher risk patients, case reports, and reports that included injuries resulting from obstetric or oncologic procedures. TABULATION, INTEGRATION, AND RESULTS: Data from each report were classified according to type of surgery into vaginal hysterectomy, abdominal hysterectomy, laparoscopic hysterectomy, other (nonrobotic) gynecologic and urogynecologic surgery, robotic hysterectomy, and other robotic gynecologic and urogynecologic surgery. We determined the ureteric and bladder injury rates for each surgery type from studies in which routine intraoperative cystoscopy was performed and separately from studies in which it was not performed. Intraoperatively detected rates of ureteric and bladder injury were markedly higher with routine intraoperative cystoscopy. We obtained an adjusted ureteric injury rate of 0.3% and a bladder injury rate of 0.8%. The estimated postoperative ureteric injury detection rates per 1,000 surgeries were 1.6 without routine cystoscopy and 0.7 with routine cystoscopy. Postoperative bladder injury detection rates per 1,000 surgeries were 0.8 without routine cystoscopy and 1.0 with routine cystoscopy. CONCLUSION: Although routine cystoscopy clearly increases the intraoperative detection rate of urinary tract injuries, this systematic review of 79 mostly retrospective studies shows that it does not appear to have much effect on the postoperative injury detection rate. PMID- 26551174 TI - Treatment of Aggressive Pelvic Fibromatosis With Interferon. AB - BACKGROUND: Fibromatosis is a rare, noninvasive but aggressive tumor. The tumor displaces tissue by "pushing" the normal structures aside. Optimal treatment should be individualized. CASE: A 35-year-old woman presented with a recurrent fibromatosis, which filled the vagina and extended into the pelvis. The classical surgical removal would have had a high morbidity. Therefore, it was decided, after shared decision-making, to opt for treatment with interferon. The side effects of the therapy were tolerable, and a complete regression of the fibromatosis was achieved. At present, 13 years after the diagnosis and 7 years after discontinuation of the therapy, the patient is well with no signs of disease. CONCLUSION: Interferon may be considered as primary treatment for extensive pelvic fibromatosis. PMID- 26551175 TI - A Multi-State Analysis of Early-Term Delivery Trends and the Association With Term Stillbirth. AB - OBJECTIVE: To investigate whether reduction in early-term deliveries was associated with increasing rates of term stillbirth. METHODS: This is a retrospective descriptive analysis of variation in term delivery timing and stillbirth from 2005 to 2011 based on birth certificate and fetal death data. Early-term deliveries (37 0/7-38 6/7 weeks of gestation) as a percentage of total term delivery and term stillbirth rates were calculated for each state, both overall and for low- and high-risk women. We analyzed whether state-level changes in early-term deliveries and term stillbirth were correlated using Pearson correlation coefficients. States were also categorized as high or low reduction (above or below the national average) and changes in stillbirth rates for these groups were analyzed using a Cochrane-Armitage test for linear trend. RESULTS: There was a decline in early-term deliveries across the United States: 1,123,467 of 3,533,233 term, singleton births occurred in the early term in 2005 (31.8%) as compared with 978,294 of 3,429,172 (28.5%) in 2011. Reductions varied widely by state. There was no change in the term stillbirth rate (123/100,000 births in 2005 compared with 130/100,000 in 2011; P=.189) nor change in the high reduction states alone. There was no correlation between state-level changes in early-term deliveries and term stillbirth. There was an increase in term stillbirths among women with diabetes (from 238/100,000 to 300/100,000 births; P=.010), independent of changes in early-term delivery timing. CONCLUSION: The reduction in early-term deliveries across the United States between 2005 and 2011 was not associated with an increase in the rate of term stillbirth. LEVEL OF EVIDENCE: II. PMID- 26551176 TI - Yoga in Pregnancy: An Examination of Maternal and Fetal Responses to 26 Yoga Postures. AB - OBJECTIVE: To examine the acute maternal and fetal effects of yoga postures and suspected contraindicated postures in a prospective cohort of healthy pregnant women in the third trimester. METHODS: This was a prospective study that evaluated pregnant women between 35 0/7 and 37 6/7 weeks of gestation in a one-on one yoga session. A baseline nonstress test, vital signs, and pulse oximetry were performed. Participants then assumed 26 yoga postures. Vital signs, pulse oximetry, tocometry, and continuous fetal heart rate monitoring were obtained in each posture. Postsession nonstress test, vital signs, and pulse oximetry were obtained. Participants were contacted 24 hours postsession. RESULTS: Twenty-five healthy pregnant women were evaluated. Ten reported regular yoga practice, eight were familiar with yoga, and seven had no yoga experience. Yoga groups were similar in age, race, body mass index, gestational age, and parity. Presession and postsession nonstress tests were reactive. Presession and postsession data showed no change in maternal heart rate, temperature, pulse oximetry, or fetal heart rate. During the 26 yoga postures, vital signs, pulse oximetry, and uterine tocometry remained normal in all women and in all postures. The fetal heart rate across all 26 postures was normal. There were no falls or injuries during the total cumulative 650 poses. No participants reported decreased fetal movement, contractions, leakage of fluid, or vaginal bleeding in the 24-hour follow-up. CONCLUSION: All 26 yoga postures were well-tolerated with no acute adverse maternal physiologic or fetal heart rate changes. LEVEL OF EVIDENCE: III. PMID- 26551177 TI - Gender Differences in Scholarly Productivity Within Academic Gynecologic Oncology Departments. AB - OBJECTIVE: To estimate whether there is a gender difference in scholarly productivity among academic gynecologic oncologists. METHODS: In this cross sectional study, the academic rank and gender of gynecologic oncology faculty in the United States were determined from online residency and fellowship directories and departmental web sites. Each individual's h-index and years of publication were determined from Scopus (a citation database of peer-reviewed literature). The h-index is a quantification of an author's scholarly productivity that combines the number of publications with the number of times the publications have been cited. We generated descriptive statistics and compared rank, gender, and productivity scores. RESULTS: Five hundred seven academic faculty within 137 U.S. teaching programs were identified. Of these, 215 (42%) were female and 292 (58%) were male. Men had significantly higher median h indices than women, 16 compared with 8, respectively (P<.001). Women were more likely to be of junior academic rank with 63% of assistant professors being female compared with 20% of full professors. When stratifying h-indices by gender and academic rank, men had significantly higher h-indices at the assistant professor level (7 compared with 5, P<.001); however, this difference disappeared at the higher ranks. Stratifying by the years of active publication, there was no significant difference between genders. CONCLUSION: Female gynecologic oncologists at the assistant professor level had lower scholarly productivity than men; however, at higher academic ranks, they equaled their male counterparts. Women were more junior in rank, had published for fewer years, and were underrepresented in leadership positions. LEVEL OF EVIDENCE: III. PMID- 26551178 TI - A Cost-Benefit Analysis of Low-Dose Aspirin Prophylaxis for the Prevention of Preeclampsia in the United States. AB - OBJECTIVE: To develop a decision model to evaluate the risks, benefits, and costs of different approaches to aspirin prophylaxis for the approximately 4 million pregnant women in the United States annually. METHODS: We created a decision model to evaluate four approaches to aspirin prophylaxis in the United States: no prophylaxis, prophylaxis per American College of Obstetricians and Gynecologists (the College) recommendations, prophylaxis per U.S. Preventive Services Task Force recommendations, and universal prophylaxis. We included the costs associated with aspirin, preeclampsia, preterm birth, and potential aspirin associated adverse effects. TreeAge Pro 2011 was used to perform the analysis. RESULTS: The estimated rate of preeclampsia would be 4.18% without prophylaxis compared with 4.17% with the College approach in which 0.35% (n=14,000) of women receive aspirin, 3.83% with the U.S. Preventive Services Task Force approach in which 23.5% (n=940,800) receive aspirin, and 3.81% with universal prophylaxis. Compared with no prophylaxis, the U.S. Preventive Services Task Force approach would save $377.4 million in direct medical care costs annually, and universal prophylaxis would save $365 million assuming 4 million births each year. The U.S. Preventive Services Task Force approach is the most cost-beneficial in 79% of probabilistic simulations. Assuming a willingness to pay of $100,000 per neonatal quality-adjusted life-year gained, the universal approach is the most cost effective in more than 99% of simulations. CONCLUSION: Both the U.S. Preventive Services Task Force approach and universal prophylaxis would reduce morbidity, save lives, and lower health care costs in the United States to a much greater degree than the approach currently recommended by the College. PMID- 26551179 TI - Association of Women's Reproductive History With Long-term Mortality and Effect of Socioeconomic Factors. AB - OBJECTIVE: To assess the effects of socioeconomic factors on the association between parity and long-term maternal mortality. METHODS: This was a population based cohort study of mothers with births registered in the Medical Birth Registry of Norway during the period 1967-2009. We estimated age-specific (40-69 years) cardiovascular and noncardiovascular mortality ratios by number of births using Cox proportional hazard models. To assess effect modification by mothers' attained education, we stratified on low (less than 11 years) and high (11 years or greater) educational level. We further evaluated fathers' mortality by number of births using the same analytical approach. RESULTS: Mothers with low education had higher mortality (cardiovascular: hazard ratio 2.62, 95% confidence interval [CI] 2.34-2.93, noncardiovascular: hazard ratio 1.67, 95% CI 1.62-1.73). Among mothers with low education, cardiovascular mortality increased linearly with each additional birth above one (P trend=.02). In contrast, among mothers with high education, cardiovascular mortality declined with added births (P trend=.045). For noncardiovascular mortality there was no association among mothers with low education, whereas mortality declined with increasing number of births among mothers with high education (P trend<.01). Father's mortality showed similar associations with number of births when stratified on maternal education. CONCLUSION: Women's long-term mortality rose with number of births only for cardiovascular causes of death and only among mothers with low education. Partners of women with low education had similar increasing risk with increasing number of births. Maternal educational level is a strong modifier of the association between parity and long-term mortality. LEVEL OF EVIDENCE: II. PMID- 26551181 TI - The Likelihood of Change in Fetal Presentation During the Third Trimester in Twin Pregnancies. AB - OBJECTIVE: To estimate the likelihood and identify predictors of spontaneous fetal version during the third trimester in twins using data from a multicenter randomized controlled trial on mode of delivery in twin pregnancies. METHODS: Women with twin pregnancies after 32 weeks of gestation in which twin A was vertex were randomized to planned cesarean or planned vaginal delivery. In the current study we analyzed the likelihood of a spontaneous version of any of the twins between ultrasound assessment at the time of randomization and delivery. RESULTS: A total of 2,603 women were analyzed. Twin A tended to persist in the vertex presentation after 32 weeks of gestation with a spontaneous version rate to nonvertex presentation of 3.0% (95% confidence interval [CI] 2.3-3.7%). Twin B was less stable and underwent spontaneous version in 24.8% (95% CI 23.1-26.5%) of cases; the rate remained higher than 20% even after 34 weeks of gestation. On multivariable analysis, twin A was more likely to undergo version when twin B was smaller (adjusted odds ratio [OR] 2.0, 95% CI 1.04-3.3), when twin B was breech (adjusted OR 3.7, 95% CI 2.2-6.4) or transverse (adjusted OR 2.9, 95% CI 1.6 5.5), and when the interval to delivery exceeded 4 weeks (adjusted OR 2.5, 95% CI 1.3-5.0). Twin B was more likely to undergo version when it was in the breech presentation (adjusted OR 1.7, 95% CI 1.4-2.1) or transverse lie (adjusted OR 3.1, 95% CI 2.5-3.9) compared with vertex presentation, when it was smaller (adjusted OR 1.7, 95% CI 1.1-2.0), when the interval to delivery exceeded 4 weeks (adjusted OR 1.7, 95% CI 1.3-2.4), and in multiparous women (adjusted OR 1.3, 95% CI 1.04-1.5). CONCLUSION: The likelihood of spontaneous version of twin A after 32 weeks of gestation is low when twin A is in the vertex presentation but is much higher for twin B, even late during the third trimester. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187369. LEVEL OF EVIDENCE: II. PMID- 26551180 TI - Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women. AB - OBJECTIVE: To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. METHODS: A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. RESULTS: There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). CONCLUSION: Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. LEVEL OF EVIDENCE: II. PMID- 26551182 TI - Association of Preoperative Thrombocytosis and Leukocytosis With Postoperative Morbidity and Mortality Among Patients With Ovarian Cancer. AB - OBJECTIVE: To examine whether preoperative thrombocytosis or leukocytosis is associated with increased postoperative morbidity or mortality. METHODS: Patients with ovarian cancer undergoing primary surgery from 2005 to 2012 were identified from the American College of Surgeons National Surgical Quality Improvement Project. Thrombocytosis was defined as platelets greater than 450,000/mm and leukocytosis as white blood cells greater than 10,000/mm. We examined 30-day postoperative complications and mortality. Descriptive statistics and adjusted multivariable logistic regression were used for analysis. RESULTS: We identified 1,072 patients. The incidence of thrombocytosis was 9.6%, leukocytosis was 18.7%, and 4.9% had both. Leukocytosis was associated with major complication (16.5% compared with 10.3%, P=.01) but not postoperative death (3.0% compared with 1.3%, P=.08). Thrombocytosis was also associated with major complication (19.4% compared with 10.7%, P<.01) but not postoperative death (2.9% compared with 1.5%, P=.30). Patients with both thrombocytosis and leukocytosis had increased rates of both major complication (22.6% compared with 10.9%, P<.001) and mortality (5.7% compared with 1.4%, P=.02). In logistic regression adjusting for age, comorbidities, and surgical complexity, major complication remained associated with thrombocytosis (adjusted odds ratio [OR] 2.16, 95% confidence interval [CI], 1.25-3.74, P<.01) and leukocytosis (adjusted OR 1.78, 95% CI, 1.13-2.80, P=.01). Additionally, thrombocytosis and leukocytosis together were associated with postoperative death (adjusted OR 5.4, 95% CI, 1.4-22.3, P=.02). CONCLUSION: Preoperative thrombocytosis or leukocytosis is associated with an increased risk of major postoperative complication. Patients with both thrombocytosis and leukocytosis experienced twice the rate of major complication and a fourfold increase in postoperative death. LEVEL OF EVIDENCE: II. PMID- 26551183 TI - Contraceptive Use Among Women With Medical Conditions in a Nationwide Privately Insured Population. AB - OBJECTIVE: To examine contraceptive use among women with selected medical conditions. METHODS: We used a nationwide health care claims database to identify women aged 15-44 years continuously enrolled in private insurance during 2004 2011 with and without selected medical conditions. We assessed current permanent and reversible prescription contraceptive use during October 1, 2010, to September 30, 2011, with diagnosis, procedure, and pharmacy codes and calculated prevalence by age and condition. We used polytomous logistic regression to calculate odds of female sterilization or reversible prescription methods compared with neither. Among users of reversible methods, we used logistic regression to calculate odds of using long-acting reversible contraceptives compared with shorter acting methods. RESULTS: A low proportion of women with medical conditions were using sterilization or reversible prescription methods (45% and 30% of women aged 15-34 and 35-44 years, respectively), and this proportion was consistently lower among the older age group across all medical conditions. Across both age groups, sterilization and long-acting reversible contraceptives were used less frequently than shorter acting methods (injectable, pill, patch, or ring). The odds of sterilization were higher among women with any compared with no condition for women aged 15-34 years (odds ratio [OR] 4.9, 95% confidence interval [CI], 4.5-5.3) and 35-44 years (OR 1.2, 95% CI, 1.1-1.2). Among women using reversible prescription methods, the odds of using long-acting reversible contraceptives were increased among those with any compared with no condition for women aged 15-34 years (OR 2.2, 95% CI, 2.1-2.5) and 35-44 years (OR 1.1, 95% CI, 1.1-1.2). CONCLUSION: Despite the potential for serious maternal and fetal pregnancy-associated risks, contraceptive use was not optimal among women with medical conditions. LEVEL OF EVIDENCE: III. PMID- 26551184 TI - Elective Induction of Labor Compared With Expectant Management of Nulliparous Women at 39 Weeks of Gestation: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate whether the elective induction of labor in nulliparous women with an unfavorable cervix affects the cesarean delivery rate. METHODS: We conducted a randomized controlled trial at a tertiary care medical center. Nulliparous woman between 38 0/7 and 38 6/7 weeks of gestation who were least 18 years of age with a singleton gestation and a Bishop score of 5 or less were randomized to elective induction of labor or expectant management. The induction of labor group was induced within 1 week of enrollment but not before 39 0/7 weeks of gestation. The control group continued routine prenatal care with admission for labor or obstetric indication. The primary outcome was cesarean delivery. Assuming a 20% rate in women in a control group, 80% power, and a goal to detect a twofold increase to 40% in the induction of labor group, 162 patients were needed. RESULTS: From March 2010 to February 2014, 82 patients were randomly allocated to induction of labor and 80 to expectant management. Baseline characteristics were similar between groups. The cesarean delivery rate in the induction of labor group was 30.5% (25/82) compared with 17.7% (14/79) in the expectant management group (relative risk 1.72, 95% confidence interval 0.96 3.06). CONCLUSION: In nulliparous women with a Bishop score of 5 or less, elective induction after 39 0/7 weeks of gestation compared with expectant management of pregnancy did not double the rate of cesarean delivery. CLINICAL TRIAL REGISTRACTION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01076062. LEVEL OF EVIDENCE: I. PMID- 26551185 TI - Women's Health Care Teams and the Future of Obstetrics and Gynecology. AB - Health care delivery is in a stage of transformation and a meaningful change in provision of care must also be accompanied by changes in the educational process of health care professionals. This article lays out a roadmap to better prepare obstetrician-gynecologists (ob-gyns) to succeed in interdisciplinary women's health care teams. Just as our current educational programs emphasize the development of competent surgical skills, our future programs must encourage and support the development of communication, teamwork, and leadership skills for ob gyns. Formal integration of these fundamentals at all levels of the health care training continuum will create an educational system designed to equip all practitioners with a basic level of knowledge and provide opportunities to acquire additional knowledge and skills as needs and interest dictate. Integral to the implementation will be the evaluation of the effects of the contributions of interprofessional education on patient, practice, and health system outcomes. Successful demonstration of value will lead to the sustainability of the educational programs through recognition by physicians, health care teams, academia, health care systems, and payers. PMID- 26551186 TI - Maternal and Neonatal Outcomes by Attempted Mode of Operative Delivery From a Low Station in the Second Stage of Labor. AB - OBJECTIVE: To evaluate maternal and neonatal outcomes by attempted mode of operative delivery from a low station in the second stage of labor. METHODS: Retrospective study of 2,518 women carrying singleton fetuses at 37 weeks of gestation or greater who underwent attempted forceps-assisted delivery, attempted vacuum-assisted vaginal delivery, or cesarean delivery from a low station in the second stage of labor. Primary outcomes were stratified by parity and included a maternal adverse outcome composite (postpartum hemorrhage, transfusion, endometritis, peripartum hysterectomy, or intensive care unit admission) and a neonatal adverse outcome composite (5-minute Apgar score less than 4, respiratory morbidity, neonatal intensive care unit admission, shoulder dystocia, birth trauma, or sepsis). RESULTS: In nulliparous patients, the maternal adverse composite was not significantly different between women who underwent attempted forceps (12.1% compared with 10.8%, adjusted odds ratio [OR] 0.77, 95% confidence interval [CI] 0.40-1.34) or vacuum (8.3% compared with 10.8%, adjusted OR 0.68, 95% CI 0.40-1.16) delivery compared with cesarean delivery. Among parous women, the maternal adverse composite was not significantly different with attempted forceps (10.7% compared with 12.5%, adjusted OR 0.40, 95% CI 0.09-1.71) or vacuum (11.3% compared with 12.5%, adjusted OR 0.44, 95% CI 0.11-1.72) compared with cesarean delivery. Compared with neonates delivered by cesarean, the neonatal adverse composite was significantly lower among neonates born to nulliparous women who underwent attempted forceps (9.4% compared with 16.7%, adjusted OR 0.44, 95% CI 0.27-0.72) but not among those who underwent vacuum delivery (11.9% compared with 16.7%, adjusted OR 0.68, 95% CI 0.44-1.04). Among parous women, the neonatal adverse composite was not significantly different after attempted forceps (4.1% compared with 12.5%, adjusted OR 0.28, 95% CI 0.06-1.35) or vacuum (12.5% compared with 12.5%, adjusted OR 1.03, 95% CI 0.28-3.87) compared with cesarean delivery. CONCLUSION: A trial of forceps delivery from a low station compared with cesarean delivery was associated with decreased neonatal morbidity among neonates born to nulliparous women. LEVEL OF EVIDENCE: II. PMID- 26551187 TI - Management for Elderly Women With Advanced-Stage, High-Grade Endometrial Cancer. AB - OBJECTIVE: To examine the treatment and survival of elderly women diagnosed with advanced-stage, high-grade endometrial cancer. METHODS: We performed a retrospective cohort study of women diagnosed between 2003 and 2011 with advanced stage, high-grade endometrial cancers (grade 3 adenocarcinoma, carcinosarcoma, clear-cell carcinoma, and uterine serous carcinoma) using the National Cancer Database. Women were stratified by age: younger than 55, 55-64, 65-74, 75-84, and 85 years old or older. Multivariate logistic regression models and Cox proportional hazards survival methods for all-cause mortality were used for analyses. RESULTS: Twenty thousand four hundred sixty-eight patients were included, 14.9% younger than 55 years, 30.9% 55-64 years, 31.1% 65-74 years, 18.8% 75-84 years, and 4.3% 85 years old or older. Patients younger than 55 years had surgery more frequently compared with patients 75-84 years (97.2% compared with 95.8%; P<.001) and 85 years or older (97.2% compared with 94.8%; P<.001) and a higher rate of lymph node dissection (78.7% compared with 70.5%; P<.001 and 78.7% compared with 59.5%; P<.001, respectively). Women younger than 55 years old were more likely to receive chemotherapy compared with those 75-84 years (63.9% compared with 42.2%; P<.001) and 85 years old or older (63.9% compared with 22%; P<.001). After adjusting for prognostic factors, women ages 75-84 and 85 years or older were less likely to have received chemotherapy compared with women younger than 55 years (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.29-0.38 and OR 0.12, 95% CI 0.10-0.14). The same was true with surgery (OR 0.63, 95% CI 0.45 0.88 and OR 0.46, 95% CI 0.30-0.70) and radiotherapy (OR 0.61, 95% CI 0.53-0.70 and OR 0.45, 95% CI 0.37-0.56). The Cox regression model showed that in women with stage III disease, women 75-84 years had a twofold higher risk of death (hazard ratio [HR] 2.38, 95% CI 2.14-2.65) and those 85 years or older had a threefold higher risk (HR 3.16, 95% CI 2.76-3.61) compared with patients younger than 55 years. Patients with stage IV and age 75-84 years had a 24% increased risk of death (HR 1.24, 95% CI 1.11-1.40) and those 85 years or older had a 52% increased risk (HR 1.52, 95% CI 1.29-1.79). CONCLUSION: Elderly women with high grade endometrial cancer are less likely to be treated with surgery, chemotherapy, or radiation. LEVEL OF EVIDENCE: II. PMID- 26551188 TI - Trends in Stillbirth by Gestational Age in the United States, 2006-2012. AB - OBJECTIVE: To evaluate stillbirth trends by gestational age. METHODS: National Center for Health Statistics' fetal death and live birth data files were used to analyze the 2006 and 2012 cohorts of deliveries and compute gestational age specific stillbirth rates at 20 weeks of gestation or greater using two methods: traditional (eg, stillbirths at 38 weeks of gestation/live births and stillbirths at 38 weeks of gestation) and prospective (stillbirths at 38 weeks of gestation/number of women still pregnant at 38 weeks of gestation). Changes in rates and in the percent distribution of stillbirths and live births were assessed. RESULTS: In 2006 and 2012, the stillbirth rate was 6.05 stillbirths per 1,000 deliveries. There was little change in the percent distribution of stillbirths by gestational age from 2006 to 2012. However, the percent distribution of live births by gestational age changed considerably: births at 34 38 weeks of gestation decreased by 10-16%, and births at 39 weeks of gestation increased by 17%. Traditionally computed stillbirth rates were unchanged at most gestational ages, but rose at 24-27, 34-36, 37, and 38 weeks of gestation. However, rates were influenced by decreases in births at those gestational ages; the pattern of stillbirths by gestational age was unchanged. In contrast, there were no differences in prospective stillbirth rates at 21-42 weeks of gestation. CONCLUSION: The lack of change in prospective stillbirth rates from 2006 to 2012 suggests that preventing nonmedically indicated deliveries before 39 weeks of gestation did not increase the U.S. stillbirth rate. LEVEL OF EVIDENCE: II. PMID- 26551189 TI - Stillbirth and the 39-Week Rule: Can We Be Reassured? PMID- 26551190 TI - Just Do It!: Routine Cystoscopy Should Be Done at the Time of Gynecologic Surgery. PMID- 26551191 TI - Every Woman, Every Time: Opportunity for Improvement. PMID- 26551192 TI - Connect the Dots... PMID- 26551193 TI - What Is New in Prevention of Perinatal Human Immunodeficiency Virus Transmission?: Best Articles From the Past Year. AB - This month we focus on current research in perinatal human immunodeficiency virus transmission. Dr. Jamieson discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts. PMID- 26551194 TI - Recommendations for Follow-up Care for Gynecologic Cancer Survivors. AB - Gynecologic cancer survivors are expected to increase in number over the coming years. This is attributable in part to an increased incidence of gynecologic malignancies as the population ages. Earlier detection and improved treatments will lead to improved survival. Women who have completed their cancer treatment and are disease-free enter a phase of follow-up care. This care can be provided by gynecologic oncologists, general gynecologists, or primary care practitioners, depending on local practices and geographic area. The key components of follow-up include complete history and physical examination. There should be judicious use of appropriate testing to detect disease recurrence, assessment, and management of therapy-related symptoms and provision of psychosocial support. Well-woman care and ongoing screening for other malignancies remain an important component of care that should not be overlooked. This review provides recommendations regarding follow-up care for women with gynecologic malignancies. There is very little high-quality evidence available to guide such care. PMID- 26551195 TI - Imaging System for Vaginal Surgery. AB - BACKGROUND: The vaginal surgeon is challenged with performing complex procedures within a surgical field of limited light and exposure. INSTRUMENT: The video telescopic operating microscope is an illumination and imaging system that provides visualization during open surgical procedures with a limited field of view. The imaging system is positioned within the surgical field and then secured to the operating room table with a maneuverable holding arm. A high-definition camera and Xenon light source allow transmission of the magnified image to a high definition monitor in the operating room. The monitor screen is positioned above the patient for the surgeon and assistants to view real time throughout the operation. EXPERIENCE: The video telescopic operating microscope system was used to provide surgical illumination and magnification during total vaginal hysterectomy and salpingectomy, midurethral sling, and release of vaginal scar procedures. All procedures were completed without complications. The video telescopic operating microscope provided illumination of the vaginal operative field and display of the magnified image onto high-definition monitors in the operating room for the surgeon and staff to simultaneously view the procedures. CONCLUSION: The video telescopic operating microscope provides high-definition display, magnification, and illumination during vaginal surgery. PMID- 26551196 TI - Skin Preparation for Prevention of Surgical Site Infection After Cesarean Delivery: A Randomized Controlled Trial. AB - OBJECTIVE: To compare chlorhexidine with alcohol, povidone-iodine with alcohol, and both applied sequentially to estimate their relative effectiveness in prevention of surgical site infections after cesarean delivery. METHODS: Women undergoing nonemergent cesarean birth at greater than 37 0/7 weeks of gestation were randomly allocated to one of three antiseptic skin preparations: povidone iodine with alcohol, chlorhexidine with alcohol, or the sequential combination of both solutions. The primary outcome was surgical site infection reported within the first 30 days postpartum. Based on a surgical site infection rate of 12%, an anticipated 50% reduction for the combination group relative to either single skin preparation group, with a power of 0.90 and an alpha of 0.05, 430 women per group were needed to detect a difference. RESULTS: From January 2013 to July 2014, 1,404 women were randomly assigned to one of three groups: povidone-iodine with alcohol (n=463), chlorhexidine with alcohol (n=474), or both (n=467). The groups were similar with respect to demographics, medical disorders, indication for cesarean delivery, operative time, and blood loss. The overall rate of surgical site infection-4.3%-was lower than anticipated. The skin preparation groups had similar surgical site infection rates: povidone-iodine 4.6%, chlorhexidine with alcohol 4.5%, and sequential 3.9% (P=.85). CONCLUSION: The skin preparation techniques resulted in similar rates of surgical site infections. Our study provides no support for any particular method of skin preparation before cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01870583. LEVEL OF EVIDENCE: I. PMID- 26551197 TI - Gene expression and metabolic responses of HepG2/C3A cells exposed to flame retardants and dust extracts at concentrations relevant to indoor environmental exposures. AB - Humans are routinely exposed to mixtures of flame retardants (FRs) from multiple sources including indoor dust. As a model to explore the potential effects of FR exposure from indoor dust on human health, the molecular responses of human hepatoma cells (HepG2/C3A cells) to a defined mixture of FRs and to a dust extract were investigated using multiple non-targeted omics approaches. A solvent extract of an indoor dust standard reference material SRM2585 was used as the surrogate dust sample, while a mixture of four FRs (TCEP, TCIPP, TDCIPP and HBCD) was used to mimic the FR mixture in the indoor dust. Cytotoxicity tests indicated there were no significant changes to cell viability or cell integrity after a 24- or 72-h exposure of HepG2/C3A cells to the FR mixture or to the dust extract. However, transcriptomics revealed changes in gene expression associated with the metabolism of xenobiotics (e.g. CYP1A1, CYP1A2, CYP2B6) in the dust extract group but not in the FR mixture group after a 72-h exposure. Few metabolic or lipidomic changes were detected in response to either the FR mixture or to the dust extract group. Given that the dust extract contained components that elicited a biological response, in contrast to the lack of response induced by the FR mixture, our findings suggest that the most likely causes of the molecular responses to indoor dust exposure lie in components other than the four FRs investigated, e.g. caused by PAHs or PCBs. PMID- 26551198 TI - Effects of formaldehyde exposure on anxiety-like and depression-like behavior, cognition, central levels of glucocorticoid receptor and tyrosine hydroxylase in mice. AB - Formaldehyde exposure is toxic to the brains of mammals, but the mechanism remains unclear. We investigated the effects of inhaled formaldehyde on anxiety, depression, cognitive capacity and central levels of glucocorticoid receptor and tyrosine hydroxylase in mice. After exposure to 0, 1 or 2 ppm gaseous formaldehyde for one week, we measured anxiety-like behavior using open field and elevated plus-maze tests, depression-like behavior using a forced swimming test, learning and memory using novel object recognition tests, levels of glucocorticoid receptors in the hippocampus and tyrosine hydroxylase in the Arc, MPOA, ZI and VTA using immuhistochemistry. We found that inhalation of 1 ppm formaldehyde reduced levels of anxiety-like behavior. Inhalation of 2 ppm formaldehyde reduced body weight, but increased levels of depression-like behavior, impaired novel object recognition, and lowered the numbers of glucocorticoid receptor immonureactive neurons in the hippocampus and tyrosine hydroxylase immonureactive neurons in the ventral tegmental area and the zona incerta, medial preoptic area. Different concentrations of gaseous formaldehyde result in different effects on anxiety, depression-like behavior and cognition ability which may be associated with alterations in hippocampal glucocorticoid receptors and brain tyrosine hydroxylase levels. PMID- 26551200 TI - Introduction to the Theme "Cancer Pharmacology". PMID- 26551199 TI - Nanoparticulate mineral matter from basalt dust wastes. AB - Ultra-fine and nano-particles derived from basalt dust wastes (BDW) during "stonemeal" soil fertilizer application have been the subject of some concern recently around the world for their possible adverse effects on human health and environmental pollution. Samples of BDW utilized were obtained from companies in the mining district of Nova Prata in southern Brazil for chemical characterization and nano-mineralogy investigation, using an integrated application of advanced characterization techniques such as X-ray diffraction (XRD), High Resolution-Transmission Electron microscopy (HR-TEM)/(Energy Dispersive Spectroscopy) EDS/(selected-area diffraction pattern) SAED, Field Emission-Scanning Electron Microscopy (FE-SEM)/EDS and granulometric distribution analysis. The investigation has revealed that BDW materials are dominated by SiO2, Al2O3 and Fe2O3, with a complex micromineralogy including alkali feldspar, augite, barite, labradorite, hematite, heulandrite, gypsum, kaolinite, quartz, and smectite. In addition we have identified a number of trace metals such as Cd, Cu, Cr, Zn that are preferentially concentrated into the finer, inhalable, dust fraction and could so present a health hazard in the urban areas around the basalt mining zone. The implication of this observation is that use of these nanometric-sized particulates as soil fertilizer may present different health challenges to those of conventional fertilizers, inviting future work regarding the relative toxicities of these materials. Our investigation on the particle size distribution, nano-particle mineralogy and chemical composition in typical BDW samples highlights the need to develop cleaning procedures to minimise exposure to these natural fertilizing basalt dust wastes and is thus of direct relevance to both the industrial sector of basalt mining and to agriculture in the region. PMID- 26551201 TI - A Cost Analysis of Tolerance Induction for Two-Haplotype Match Kidney Transplant Recipients. PMID- 26551203 TI - Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells. AB - Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 MUM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies. PMID- 26551204 TI - Comparative characterization of nucleotides, nucleosides and nucleobases in Abelmoschus manihot roots, stems, leaves and flowers during different growth periods by UPLC-TQ-MS/MS. AB - Nucleotides, nucleosides and nucleobases have been proven as important bioactive compounds related to many physiological processes. Abelmoschus manihot (L.) Medicus from the family of Malvaceae is an annual herbal plant of folk medicine widely distributed in Oceania and Asia. However, up to now, no detailed information could be available for the types and contents of nucleotides, nucleosides and nucleobases contained in A. manihot roots, stems, leaves as well as the flowers. In the present study, an UPLC-TQ-MS/MS method was established for detection of the twelve nucleotides, nucleosides and nucleobases. The validated method was successfully applied to identify the 12 analytes in different parts of A. manihot harvested at ten growth periods. 2'-deoxyinosine was not detected in all of the A. manihot samples. The data demonstrated that the distribution and concentration of the 12 compounds in A. manihot four parts were arranged in a decreasing order as leaf>flower>stem>root. Based on the results, the leaves and flowers of A. manihot could be developed as health products possessed nutraceutical and bioactive properties in the future. This method might also be utilized for the quality control of the A. manihot leaves and other herbal medicines being rich in nucleotides, nucleosides and nulecobases. PMID- 26551202 TI - Raw Sap Consumption Habits and Its Association with Knowledge of Nipah Virus in Two Endemic Districts in Bangladesh. AB - Human Nipah virus (NiV) infection in Bangladesh is a fatal disease that can be transmitted from bats to humans who drink contaminated raw date palm sap collected overnight during the cold season. Our study aimed to understand date palm sap consumption habits of rural residents and factors associated with consumption. In November-December 2012 the field team interviewed adult respondents from randomly selected villages from Rajbari and Kushtia Districts in Bangladesh. We calculated the proportion of people who consumed raw sap and had heard about a disease from raw sap consumption. We assessed the factors associated with raw sap consumption by calculating prevalence ratios (PR) adjusted for village level clustering effects. Among the 1,777 respondents interviewed, half (50%) reported drinking raw sap during the previous sap collection season and 37% consumed raw sap at least once per month. Few respondents (5%) heard about NiV. Thirty-seven percent of respondents reported hearing about a disease transmitted through raw sap consumption, inclusive of a 10% who related it with milder illness like diarrhea, vomiting or indigestion rather than NiV. Respondents who harvested date palm trees in their household were more likely to drink sap than those who did not own date palm trees (79% vs. 65% PR 1.2, 95% CI 1.1-1.3, p<0.001). When sap was available, respondents who heard about a disease from raw sap consumption were just as likely to drink it as those who did not hear about a disease (69% vs. 67%, PR 1.0, 95% CI 0.9-1.1, p = 0.512). Respondents' knowledge of NiV was low. They might not have properly understood the risk of NiV, and were likely to drink sap when it was available. Implementing strategies to increase awareness about the risks of NiV and protect sap from bats might reduce the risk of NiV transmission. PMID- 26551205 TI - Separation and purification of two new and two known alkaloids from leaves of Nitraria sibirica by pH-zone-refining counter-current chromatography. AB - The total alkaloids from Nitraria sibirica leaves have been confirmed to exhibit significant protective effects against inflammatory renal injury, hypertension and albuminuria in angiotensin II-salt hypertension. In the present study, a separation method of pH-zone-refining counter-current chromatography was established for separation of the alkaloids from N. sibirica. The separation was performed with a solvent system of MtBE-n-BuOH-H2O (2:2:5, v/v) at a flow rate of 2.0mL/min. And 15mM triethylamine (TEA) was added to the upper organic phase, while 10mM hydrochloric acid was added to the lower aqueous phase. As a result, a new alkaloid, schobemine (5.6mg), and a known alkaloid, nitraramine (5.0mg), together with fractions A and B were obtained from the total alkaloids of N. sibirica. The fractions A and B were further purified by means of pH-zone refining counter-current chromatography with solvent systems of n-hexane-n-BuOH H2O (1.5:3.5:5, v/v) and (2:3:5, v/v), respectively. TEA (10mM) was added to the upper phase, and 10mM of HCl was added to the lower phase in above two solvent systems, respectively. As a result, a known alkaloid, schoberidine (5.0mg), and a new alkaloid, schoberimine (3.0mg) were obtained from fractions A and B, respectively. The purities of the compounds were measured by HPLC-ELSD, and their structures were identified by ESI-MS, 1D and 2D NMR. PMID- 26551206 TI - Capillary electrophoresis with end-column electrochemiluminescence for ultrasensitive determination of urapidil hydrochloride in rat plasma and its application to pharmacokinetics study. AB - A simple, sensitive and selective method for determination of urapidil hydrochloride was developed using capillary electrophoresis with electrochemiluminescence (CE-ECL) technique for the first time. Under the optimized experimental conditions, the ECL intensity was linear with the concentration of urapidil hydrochloride in the range from 0.050 to 50.0ng/mL and the detection limit was 0.014ng/mL (S/N=3). The proposed method was used for studying pharmacokinetics of urapidil hydrochloride in rat plasma and the main pharmacokinetic parameters of the peak concentration (Cmax), half life time (T1/2) and peak concentration time (Tmax) were 240.45+/-21.15ng/mL, 0.58+/-0.16h and 1.08+/-0.13h, respectively. The recoveries of urapidil hydrochloride in the diluted extracts of rat plasma samples ranged from 96.68 to 98.82%. The RSD was lower than 3%. PMID- 26551207 TI - Determination of residual arsenic compounds in chicken muscle by ultra performance liquid chromatography coupled with ultraviolet detection after pre column derivatization with toluene-3,4-dithiol. AB - A simple and sensitive derivatization method using toluene-3,4-dithiol as a derivatization reagent for the simultaneous analysis of seven arsenic compounds (roxarsone, nitarsone, p-arsanilic acid, o-arsanilic acid, phenylarsonic acid, phenylarsine oxide, and mono-methylarsonic acid) in chicken muscle was developed and validated by ultra-performance liquid chromatography coupled with ultraviolet detection (UPLC-UV). The structure of the derivatized arsenic compounds was confirmed by liquid chromatography-ion trap mass spectrometry or gas chromatography-mass spectrometry. Optimization of the derivatization reaction conditions was carried out by investigating the influence of reagent concentration, buffer or additive acids, temperature, and time. The optimized conditions were a derivatization reagent concentration of 20mg/mL with 0.05mol/L HCl as an additive acid at 60 degrees C for 15min. In this study, baseline separation of arsenic compounds could be achieved within 13min, except for phenylarsonic acid and phenylarsine oxide whose derivatized products are equal. The developed method was successfully validated and applied to 12 chicken muscle samples from Korean districts and other countries. PMID- 26551208 TI - Investigation of cell culture volatilomes using solid phase micro extraction: Options and pitfalls exemplified with adenocarcinoma cell lines. AB - Three strategies to sample volatile organic compounds (VOC) from lung cancer cell lines cultured in vitro were compared. Headspace solid phase microextraction was applied in situ to culture flasks and alternatively to subsamples of headspace gas or to nutrient solution subsamples followed by gas chromatography-mass spectrometry. The direct quantification of 55 VOC in the headspace of cell cultures was validated and is discussed with respect to reproducibility and system-related interferences. The role of the VOC background from culture media and usually employed polystyrene culture vessels is examined and was seen to invoke potentially misleading conclusions. The commercial A549 and two further adenocarcinoma cell lines displayed largely similar VOC profiles with distinct differences regarding certain individual substances. There is evidence for the inappropriateness of the standard cell culturing methods in the search for volatile cancer markers. PMID- 26551210 TI - The elution of certain protein affinity tags with millimolar concentrations of diclofenac. AB - Diclofenac (2-[(2, 6-dichlorophenyl)amino] benzeneacetic acid) is a sparingly soluble, nonsteroidal anti-inflammatory drug therapeutically acting at low micromolar concentrations. In pH range from 8 to 11, its aqueous solubility can be increased up to 200 times by the presence of counter ions such as sodium. Our protein interaction studies revealed that a millimolar concentration of sodium diclofenac is able to elute glutathione S-transferase (GST), cellulose binding protein (CBD), and maltose binding protein (MBP) but not histidine-tagged or PDZ tagged proteins from their affinity resins. The elution efficiency of diclofenac is comparable with the eluting agents normally used at similar concentrations. Native gel electrophoresis of sodium diclofenac-treated proteins showed that the interaction is non-covalent and non-denaturing. These results suggest that sodium diclofenac, in addition to its pharmaceutical applications, can also be exploited as a lead for the development of new proteomics reagents. PMID- 26551209 TI - Quantitative analysis of intracellular nucleoside triphosphates and other polar metabolites using ion pair reversed-phase liquid chromatography coupled with tandem mass spectrometry. AB - Simultaneous, quantitative determination of intracellular nucleoside triphosphates and other polar metabolites using liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS) represents a bioanalytic challenge because of charged, highly hydrophilic analytes presented at a large concentration range in a complex matrix. In this study, an ion pair LC MS/MS method using triethylamine (TEA)-hexafluoroisopropanol (HFIP) ion-pair mobile phase was optimized and validated for simultaneous and unambiguous determination of 8 nucleoside triphosphates (including ATP, CTP, GTP, UTP, dATP, dCTP, dGTP, and dTTP) in cellular samples. Compared to the the less volatile ion pair reagent, triethylammonium acetate (100mM, pH 7.0), the combination of HFIP (100mM) and TEA (8.6mM) increased the MS signal intensity by about 50-fold, while retaining comparable chromatographic resolution. The isotope-labeled internal standard method was used for the quantitation. Lower limits of quantitation were determined at 0.5nM for CTP, UTP, dATP, dCTP, and dTTP, at 1nM for ATP, and at 5nM for GTP and dGTP. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method validation (<15%). While the present method was validated for the quantitation of intracellular nucleoside triphosphates, it had a broad application potential for quantitative profiling of nucleoside mono- and bi-phosphates as well as other polar, ionic metabolic intermediates (including carbohydrate derivatives, carboxylic acid derivatives, co-acyl A derivatives, fatty acyls, and others) in biological samples. PMID- 26551211 TI - The Usage Behavior and Intention Stability of Nurses: An Empirical Study of a Nursing Information System. AB - BACKGROUND: Many prior studies of technology adoption treat user intention as the single predictor of actual usage behavior. However, as many researchers of behavioral science have pointed out, multiple factors mediate the relationship between user intention and usage behavior. PURPOSE: The present article explores the factors that mediate the relationship between intention and actual behavior. We develop a conceptual framework that is based on the Technology Acceptance Model III and behavior theory to further elicit system usage behavior and to confirm "intention stability" and "past experience" as two significant mediating factors in this relationship. METHODS: The target system was a nursing information system that had been recently adopted by a medical center in central Taiwan. Data were collected using a questionnaire survey conducted in two rounds. Two hundred forty-five valid questionnaires were returned (response rate: 49%). Mediated moderation was analyzed to explore the presence of mediators or moderators between intention and behavior. RESULTS: The results support that intention stability is a mediated moderator and that prior experience is a moderator of the relationship between intention and behavior. These two factors increased by over 13.6% the explanatory power of intention on actual behavior. Furthermore, this study expanded the scope of prior research by confirming intention stability as a moderating variable between intention and behavior. Finally, this study identified the moderating effect of past experience on the intention-behavior relationship, indicating that past experience enhances the predictive power of intention on behavior. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study may assist hospital managers to better understand the nursing information system usage behaviors of nursing staff and to develop ways to enhance the intention stability of these staff. Managers may improve the familiarity of nursing staff with the system by increasing their system-related practice time. More experience should enhance staff system skills and resolve problems such as the need for extra work hours or overtime because of initial system unfamiliarity. Improved work efficiency should then allow nurses to divert more time from administrative work to patient care and training. This positive circle of support is expected to increase the willingness of nurses to accept and take advantage of the system. PMID- 26551212 TI - A Comparison Study of Single-Parent Families Living on Remote, Rural Islands and in Urban Settings in Japan. AB - BACKGROUND: Nursing interventions that aim to enhance the family environment are necessary to help single-parent families with children to improve family functioning. The cultural and social factors that are unique to Japan's remote islands should be considered to assess the influence of this unique setting on family functioning. PURPOSE: The objectives of this study were to evaluate the family functioning of child-rearing single-parent families living in different environments and to investigate the association between family demographics and family functioning. METHODS: A self-administered questionnaire, the Japanese version of the Survey of Family Environment, was used to evaluate the sufficiency of family functioning. The participants were families with children enrolled in nurseries and kindergartens who were either living in remote, rural islands or in an urban city on the mainland in Japan. RESULTS: Family functioning was significantly higher for single-parent families living on the islands than for those living in the city in terms of media use, participation in community activities, and the collaboration of family members in child-rearing. Family functioning of single-parent families correlated significantly with household income, the parent's gender, family members' health, and family life cycle. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Single-parent families living on Japanese offshore islands maintained family functioning through mutual support and the effective use of information technology. Nevertheless, single-parent families require additional support to improve their healthcare and financial situations. PMID- 26551213 TI - A Study on the Effects of a Health Education Intervention on Anxiety and Pain During Colonoscopy Procedures. AB - BACKGROUND: Colonoscopy is currently considered the best screening tool in the diagnosis of colon diseases. However, this procedure often causes pain and discomfort in patients, thus reducing patient willingness to undergo and comply with this procedure. PURPOSE: This study explores the effects of providing procedure-related information to patients receiving colonoscopy in terms of anxiety and pain reduction and identifies factors that influence the pain and anxiety experienced by patients during this procedure. METHODS: This study adopted a quasi-experimental design that targeted colonoscopy patients in outpatient clinics. Two hundred thirteen patients were recruited, with 103 patients in the experimental group and 110 in the control group. Participants were recruited between January and April 2011. All of the participants received standard care, and only those participants who were assigned to the experimental group were asked to watch "A Guide to the Colonoscopy Procedure," a multimedia health informatics CD-ROM. RESULTS: Anxiety scores of the experimental group dropped from 48.7 +/- 11.6 to 39.2 +/- 8.7 after the intervention. The average pain score of the experimental group was significantly lower than that of the control group (3.8 +/- 2.5 vs. 5.0 +/- 2.7). Furthermore, trait anxiety, gender, and educational level were identified as the main predictors for state anxiety, and state anxiety was identified as an important predictor for pain during the colonoscopy examination. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study found that using a multimedia health informatics CD-ROM to provide information on the colonoscopy procedure effectively reduced the examination-related anxiety and pain of patients. PMID- 26551214 TI - The Impact of Job Involvement on Emotional Labor to Customer-Oriented Behavior: An Empirical Study of Hospital Nurses. AB - BACKGROUND: Healthcare is a profession that requires a high level of emotional labor (EL). Nurses provide frontline services in hospitals and thus typically experience high levels of EL. The quality of services that nurses provide impacts on how patients evaluate the service quality of hospitals. PURPOSE: The aim of this study is to explore the relationships among EL, job involvement (JI), and customer-oriented behavior (COB) in the context of the nursing profession. METHODS: The participants in this study were nurses at eight hospitals, all located in Taiwan. This study used a self-reporting questionnaire. Research data were gathered at two discrete periods (A and B). Questionnaire A collected data on EL and JI, and Questionnaire B collected data on COB. Five hundred questionnaires were sent out to qualified participants, and 472 valid questionnaires were returned. Hierarchical regression analysis was used to test the hypotheses. RESULTS: The expression of positive emotion (EPE) and the suppression of negative emotion (SNE) were found to positively affect the patient oriented COB. Furthermore, the EPE was found to positively affect the task oriented COB. In terms of the moderating effect of JI, JI was found to relate positively to the EPE, patient-oriented COB, and task-oriented COB. In addition, higher values of JI were found to weaken the relationship between the SNE and the task-oriented COB. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: It has become an increasingly popular practice for hospital organizations to work to promote the COB of their nursing staffs. The results of this study prove empirically that a relationship exists among EL, COB, and JI in nurses. This study contributes to the related literature, enhances the knowledge of hospital and nursing administrators with regard to EL and COB, and offers a reference for hospital managers who are responsible for designing and executing multidisciplinary programs and for managing hospital-based human resources. PMID- 26551215 TI - Psychometric Evaluation of the Cigarette Withdrawal Scale (Chinese Version) in Male Smokers in Taiwan. AB - BACKGROUND: Symptoms of smoking withdrawal are a central feature of nicotine dependence. A valid and reliable measure of these symptoms is important to better understand nicotine dependence and to develop effective interventions. PURPOSE: The objective of this study was to examine the validity and reliability of the Chinese version of the Cigarette Withdrawal Scale (CWS-C). METHODS: This study conducted cross-sectional surveys in two phases. In the first phase, exploratory factor analysis was used to test the underlying factor structure, the criterion validity, and the reliability of the CWS-C. A reliability test was conducted to assess the internal consistency and stability of the instrument. In the second phase, confirmatory factor analysis validated the factor model that had been proposed in earlier empirical research. The total sample size used in analysis was 497. RESULTS: The CWS-C achieved a level of efficacy that was similar to the English version. Exploratory factor analysis showed that the six factors of the instrument accounted for 80.3% of the variance. The full scale and all of the subscale items, with the exception of the appetite-weight gain subscale (r = .12, p = .09), were significantly associated with the Fagerstrom Test for Nicotine Dependence (r = .25-.50, p < .05). The Cronbach's alpha of the full scale was .93, with retest coefficient of .84. Confirmatory factor analysis confirmed that the CWS-C had six correlated factors. Field testing showed that the CWS-C is a reliable and valid Chinese-language instrument for assessing the symptoms of cigarette withdrawal. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The CWS-C performed well in terms of reliability and validity in several tests conducted on male Taiwanese smokers. Accurate measurement is expected to help health professionals better understand smoker quitting patterns and the severity of withdrawal symptoms and to develop improved withdrawal-symptom treatment interventions. PMID- 26551216 TI - The Effects of an Empowerment Intervention on Renal Transplant Recipients: A Randomized Controlled Trial. AB - BACKGROUND: Renal transplantation is a vital treatment for end-stage renal disease. To help improve quality of life after renal transplant surgery, interventions are needed to strengthen the coping skills and self-care behaviors of patients. However, most research studies on self-care after renal transplantation have addressed related factors. Few studies have examined the effects of interventions on renal transplant recipients. PURPOSE: This study investigated the effects of an empowerment support group on the empowerment levels and self-care behaviors of renal transplant recipients. METHODS: This study was a randomized controlled trial. Eligible participants were individuals who had undergone a renal transplant within the past 20 years, were 18 years old or older, were able to read and write in Chinese, and were willing to participate. We recruited 122 renal transplant recipients from two medical centers in southern Taiwan. The renal transplant outpatients were randomly assigned into empowerment support (n = 56) and comparison (n = 66) groups. The developed measures as well as the content, protocols, and the two groups were assessed for reliability and validity. The intervention involved one 2-hour meeting every 2 weeks for a total of six meetings. The topics included goal setting, problem solving, coping with daily stress, seeking social support, and staying motivated. The sessions consisted of introductions that highlighted the topic, group discussions, identifying areas of difficulty with self-care behaviors after renal transplant, and developing a set of goals and strategies to overcome these problems. RESULTS: The empowerment group reported significant increases both in terms of level of empowerment (F = 5.29, p = .023) based on age and time interaction (F = 9.86, p < .001) and in terms of self-care behaviors (F = 7.15, p = .009). Moreover, these increases were significantly larger than the increases recorded by the comparison group. In addition, these increases were particularly large in the older empowerment-group participants with lower pretest scores for empowerment. CONCLUSIONS: Empowerment support may be critical to improve the empowerment and self-care behaviors of renal transplant patients. The results of this study may be applied to improve patient education and empowerment programs for renal transplant patients. Furthermore, these programs may be adjusted to take into consideration the learning preferences or needs of different age groups. PMID- 26551217 TI - Flexible, Transparent, Thickness-Controllable SWCNT/PEDOT:PSS Hybrid Films Based on Coffee-Ring Lithography for Functional Noncontact Sensing Device. AB - Flexible transparent conductive films (FTCFs) as the essential components of the next generation of functional circuits and devices are presently attracting more attention. Here, a new strategy has been demonstrated to fabricate thickness controllable FTCFs through coffee ring lithography (CRL) of single-wall carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate ( PEDOT: PSS) hybrid ink. The influence of ink concentration and volume on the thickness and size of hybrid film has been investigated systematically. Results show that the final FTCFs present a high performance, including a homogeneous thickness of 60-65 nm, a sheet resistance of 1.8 kohm/sq, a visible/infrared-range transmittance (79%, PET = 90%), and a dynamic mechanical property (>1000 cycle, much better than ITO film), respectively, when SWCNT concentration is 0.2 mg/mL, ink volume is 0.4 MUL, drying at room temperature. Moreover, the benefits of these kinds of FTCFs have been verified through a full transparent, flexible noncontact sensing panel (3 * 4 sensing pixels) and a flexible battery-free wireless sensor based on a humidity sensing mechanism, showing excellent human/machine interaction with high sensitivity, good stability, and fast response/recovery ability. PMID- 26551219 TI - Co-contamination of Cu and Cd in paddy fields: Using periphyton to entrap heavy metals. AB - The ubiquitous native periphyton was used to entrap Cu and Cd from paddy fields. Results showed that Cu- and Cd-hydrate species such as CuOH(+), Cu2(OH)2(2+), CdOH(+), and Cu3(OH)4(2+) decreased with time in the presence of periphyton. When the initial concentrations of Cu and Cd were 10mg/L, the heavy metal content in the periphyton fluctuated from 145.20mg/kg to 342.42 mg/kg for Cu and from 101.75 mg/kg to 236.29 mg/kg for Cd after 2h exposure. The concentration of Cd in periphytic cells varied from 42.93 mg/kg to 174 mg/kg after 2h. The dominant periphyton microorganism species shifted from photoautotrophs to heterotrophs during the exposure of periphyton to Cu and Cd co-contamination. Although Cu and Cd could inhibit periphyton photosynthesis and carbon utilization, the periphyton was able to adapt to the test conditions. Cu and Cd accumulation in rice markedly decreased in the presence of periphyton while the number of rice seeds germinating was higher in the periphyton treatments. These results suggest that the inclusion of native periphyton in paddy fields provides a promising buffer to minimize the effects of Cu and Cd pollution on rice growth and food safety. PMID- 26551220 TI - Bioremediation of industrially contaminated soil using compost and plant technology. AB - Compost technology can be utilized for bioremediation of contaminated soil using the active microorganisms present in the matrix of contaminants. This study examined bioremediation of industrially polluted soil using the compost and plant technology. Soil samples were collected at the vicinity of three industrial locations in Ogun State and a goldmine site in Iperindo, Osun State in March, 2014. The compost used was made from cow dung, water hyacinth and sawdust for a period of twelve weeks. The matured compost was mixed with contaminated soil samples in a five-ratio pot experimental design. The compost and contaminated soil samples were analyzed using the standard procedures for pH, electrical conductivity (EC), organic carbon (OC), total nitrogen (TN), phosphorus, exchangeable cations (Na, K, Ca and Mg) and heavy metals (Fe, Mn, Cu, Zn and Cr). Kenaf (Hibiscus cannabinus) seeds were also planted for co-remediation of metals. The growth parameters of Kenaf plants were observed weekly for a period of one month. Results showed that during the one-month remediation experiment, treatments with 'compost-only' removed 49 +/- 8% Mn, 32 +/- 7% Fe, 29 +/- 11% Zn, 27 +/- 6% Cu and 11 +/- 5% Cr from the contaminated soil. On the other hand, treatments with 'compost+plant' remediated 71 +/- 8% Mn, 63 +/- 3% Fe, 59 +/- 11% Zn, 40 +/- 6% Cu and 5 +/- 4% Cr. Enrichment factor (EF) of metals in the compost was low while that of Cu (EF=7.3) and Zn (EF=8.6) were high in the contaminated soils. Bioaccumulation factor (BF) revealed low metal uptake by Kenaf plant. The growth parameters of Kenaf plant showed steady increments from week 1 to week 4 of planting. PMID- 26551218 TI - Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation. AB - The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID- 26551221 TI - Quaternary ammonium salts with tetrafluoroborate anion: Phytotoxicity and oxidative stress in terrestrial plants. AB - This paper discusses the impact of four quaternary ammonium salts (QAS) such as tetraethylammonium tetrafluoroborate [TEA][BF4], tetrabutylammonium tetrafluoroborate [TBA][BF4], tetrahexylammonium tetrafluoroborate [THA][BF4], and tetraoctylammonium tetrafluoroborate [TOA][BF4] on the growth and development of spring barley and common radish. Analogous tests were performed with the inorganic salt ammonium tetrafluoroborate [A][BF4] for comparison purposes. Results indicated that the phytotoxicity of the QAS applied is dependent on the concentration of the substance and their number of carbon atoms. The most toxic compound was [TBA][BF4], causing the greatest drop in fresh weight of both study plants, similar to the phytotoxic effects of [A][BF4]. All the tested compounds caused oxidative stress in spring barley and common radish seedlings due to a drop in the chlorophyll content. Stress was also observed in plants, which was indicated by the increased level of ROS (reactive oxygen species) such as H2O2 and lipid peroxidation of MDA (malondialdehyde). Due to the stress, both plants displayed changes in the activity of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Based on the results of the study, it was concluded that changes in chlorophyll levels and peroxidase activity are the best biomarkers to determine oxidative stress in plants. PMID- 26551222 TI - Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy. AB - Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe3O4NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe3O4NPs (B-Fe3O4NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe3O4NPs did not induce cell death within 24h even at concentrations up to 400 MUg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe3O4NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B Fe3O4NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B Fe3O4NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe3O4NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B Fe3O4NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe3O4NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation. PMID- 26551223 TI - Comparative evaluation of magnetite-graphene oxide and magnetite-reduced graphene oxide composite for As(III) and As(V) removal. AB - Arsenic removal using Fe3O4-graphene oxide composite (M-GO) and Fe3O4-reduced graphene oxide composite (M-rGO) was investigated. The M-GO was more effective to adsorb both As(III) and As(V) than M-rGO, because the more functional groups existing on the M-GO could lead to synthesize more Fe3O4 with M-GO. As(III) was more favorable to be adsorbed than As(V) onto both M-GO and M-rGO. According to the effect of pH on arsenic removal, the electrostatic interaction between the positively charged surface of Fe3O4-graphene based adsorbents and anionic As(V) species was a major factor to adsorb As(V). The adsorption mechanism of As(III), on the other hand, was strongly affected by a surface complexation, rather than electrostatic interactions. Consequently, in terms of the process energy consumption, energy saving could be achieved via omitting the reduction process to fabricate M-rGO from M-GO and the pre-oxidation process to convert As(III) to As(V). PMID- 26551224 TI - Adsorptive desulphurization study of liquid fuels using Tin (Sn) impregnated activated charcoal. AB - Keeping in view the growing concern regarding desulphurization of petroleum products, the present study was under taken to investigate the efficiency of tin impregnated activated charcoal (Sn-AC) as a potential adsorbent for the desulphurization of model and real commercial straight run kerosene and diesel oil samples. The adsorbent Sn-AC was prepared by wet impregnation process in the laboratory and characterized by SEM, EDX and surface area analysis. Initial experiments were carried out using model oil, which was prepared by dissolving dibenzothiophene (DBT) in cyclohexane, the optimum conditions for desulfurization were found to be, 60 degrees C temperature, 1h contact time and adsorbent dosage of 0.8g, under which about 99.4% of DBT removal was attained. Under optimized conditions the desulfurization of real oil i.e., kerosene and diesel oil was also investigated. Kinetic studies revealed that DBT adsorption followed pseudo second order kinetics and the data best fits in the Langmuir adsorption isotherm as compared to Freundlich adsorption isotherm model. The adsorbent could be easily regenerated simply by washing with toluene for a multiple cycles and reused without losing its efficiency. PMID- 26551226 TI - Self-flocculated powdered activated carbon with different oxidation methods and their influence on adsorption behavior. AB - The commercial powdered activated carbon (PAC) has been selectively oxidized by two methods. The two oxidized methods are wet oxidation with ammonium persulfate and thermal treatment after acidification with hydrochloride acid, respectively. The two oxidized PAC were then functionalized with thermoresponsive poly (N isopropylacrylamide) (PNIPAM) in aqueous solution at ambient temperature. Comparing the two oxidized PAC products and their grafted derivatives, the oxidized PAC modified with thermal treatment after acidification shows larger surface area of 1184 m(2)/g and better adsorption of bisphenol A. Its derivative also exhibits relatively large surface area and adsorption capacity after grafted with PNIPAM. The maximum surface adsorption capacity simulated under Langmuir Models reached 156 mg/g. In addition, the grafted PAC products show self flocculation behaviors with rapid response to temperature because of the thermal phase transition and entanglement behaviors of PNIPAM. The present study provides a new way to obtain carboxyl-rich activated carbon with large surface area and better adsorption capacity. The retrievable grafted PAC with good self flocculation effect responsive to temperature will have high potential application in water remediation which requires pre-heating and emergency water treatment in the wild. PMID- 26551225 TI - (Bio)transformation of 2,4-dinitroanisole (DNAN) in soils. AB - Recent studies have begun to assess the environmental fate and toxicity of 2,4 dinitroanisole (DNAN), an insensitive munition compound of interest to defense agencies. Aerobic and anaerobic DNAN biotransformation in soils was evaluated in this study. Under aerobic conditions, there was little evidence of transformation; most observed removal was attributed to adsorption and subsequent slow chemical reactions. Under anaerobic conditions, DNAN was reductively (bio)transformed and the rate of the transformation was positively correlated with soil organic carbon (OC) up to a threshold of 2.07% OC. H2 addition enhanced the nitroreduction rate compared to endogenous treatments lacking H2. Heat-killed treatments provided rates similar to the endogenous treatment, suggesting that abiotic factors play a role in DNAN reduction. Ten (bio)transformation products were detected by high-resolution mass spectrometry. The proposed transformation pathway involves reduction of DNAN to aromatic amines, with putative reactive nitroso-intermediates coupling with the amines to form azo dimers. Secondary reactions include N-alkyl substitution, O-demethylation (sometimes followed by dehydroxylation), and removal of an N-containing group. Globally, our results suggest that the main reaction DNAN undergoes in anaerobic soils is nitroreduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN), followed by anaerobic coupling reactions yielding azo-dimers. The dimers were subsequently subject to further (bio)transformations. PMID- 26551227 TI - A best comprehension about the toxicity of phenylsulfonyl carboxylates in Vibrio fischeri using quantitative structure activity/property relationship methods. AB - Aromatic sulfones comprise a class of chemicals used in agrochemical and pharmaceutical industries and as floatation and extractant agents in petrochemical and metallurgy industries. In this study, new QSA(P)R studies were carried out to predict the toxicity against Vibrio fischeri of a set of 52 aromatic sulfones. The same approach was used to evaluate the relationship between these endpoint and the water solubility, another important environmental endpoint. The study resulted in models of good statistical quality and mechanistic interpretation with a possible correlation between the two endpoints, but the toxic effect is also likely to depend on other physicochemical properties. The use of the PLS2, a method not commonly used in QSA(P)R studies, also produced models of greater reliability, and the relationship between the two endpoints was reinforced to some degree. These results are useful for better understanding the process by which these compounds exert their environmental toxicity, thus aiding in the development of industrially useful compounds with less potential environmental damage. PMID- 26551229 TI - Construct Validity of the Trunk Impairment Classification System in Relation to Objective Measures of Trunk Impairment. AB - OBJECTIVE: To determine the validity of the Trunk Impairment Classification system (TIC) with 4 possible scores (0, most impaired; 0.5; 1.0; 1.5, least impaired) in relation to objective, instrumented measures of impairment. DESIGN: Cross-sectional design. SETTING: National wheelchair rugby and basketball competitions of The Netherlands and Belgium. PARTICIPANTS: Volunteer sample of athletes (N=34) with a minimum of 1-year experience in their sport. INTERVENTIONS: Static sitting balance tasks on a stable and unstable surface; dynamic sitting balance tasks in anterior-posterior, left-right, and oblique directions; and trunk muscle strength tasks in forward, left, right, and backward directions. MAIN OUTCOME MEASURES: Sway area of the center of pressure in static sitting balance, maximum excursion of center of pressure displacement in dynamic sitting balance, and maximum isometric force in trunk muscle strength. RESULTS: Athletes with TIC score 0 were not able to sit unsupported. The Kruskal-Wallis test showed a significant difference in trunk muscle strength (P<.001) and dynamic balance in the oblique direction forward to the left and backward to the right between the TIC scores (P=.012). Post hoc analysis showed a significant difference between TIC score 0 and the other TIC scores for trunk muscle strength in all directions. There was a significant difference between TIC score 1.5 on one hand and TIC scores 0.5 and 1.0 on the other hand for dynamic balance in the right oblique direction. CONCLUSIONS: The TIC is a valid scale for trunk impairment, which measures neuromusculoskeletal trunk impairment, independent of the health condition causing the impairment. Additional research is needed for coordination impairment and to assess whether TIC scores 0.5 and 1.0 should continue as separate scores. PMID- 26551228 TI - Measurement of Voluntary Cough Production and Airway Protection in Parkinson Disease. AB - OBJECTIVE: To examine relations between peak expiratory (cough) airflow rate and swallowing symptom severity in participants with Parkinson disease (PD). DESIGN: Cross-sectional study. SETTING: Outpatient radiology clinic at an acute care hospital. PARTICIPANTS: Men and women with PD (N=68). INTERVENTIONS: Participants were cued to cough into an analog peak flow meter then swallowed three 20-mL thin liquid barium boluses. Analyses were directed at detecting potential relations among disease severity, swallowing symptom severity, and peak expiratory (cough) airflow rate. MAIN OUTCOME MEASURES: Peak expiratory (cough) airflow rate and swallow symptom severity. RESULTS: Peak expiratory (cough) airflow rate varied significantly across swallowing severity classifications. Participants with more severe disease displayed a significant, linear decrease in peak expiratory (cough) airflow rate than those participants with earlier stage, less severe disease. Swallowing symptom severity varied significantly across groups when comparing participants with less severe PD with those with more severe PD. Participants with early stage PD demonstrated little to no swallowing symptoms and had the highest measures of peak expiratory (cough) airflow rate. In contrast, participants with the most severe swallowing symptoms also displayed the lowest measures of peak expiratory (cough) airflow rate. CONCLUSIONS: Relations existed among PD severity, swallowing symptom severity, and peak expiratory (cough) airflow rate in participants with PD. Peak expiratory (cough) airflow rate may eventually stand as a noninvasive predictor of aspiration risk in those with PD, particularly those with later stage disease. Inclusion of peak expiratory (cough) airflow rates into existing clinical swallowing assessments may increase the sensitivity and predictive validity of these assessments. PMID- 26551230 TI - Comparison of a Cognitive-Behavioral Coping Skills Group to a Peer Support Group in a Brain Injury Population. AB - OBJECTIVE: To compare the efficacy of 2 group treatments for persons with brain injury (BI) and their caregivers in promoting perceived self-efficacy (PSE) and emotional and neurobehavioral functioning. DESIGN: Randomized controlled trial. SETTING: Outpatient BI rehabilitation. PARTICIPANTS: Subjects (N=38), including 19 with BI and 19 caregivers, participated in a BI coping skills group or a support group. INTERVENTIONS: BI coping skills is a manualized cognitive behavioral treatment (CBT). CBT was compared with a structurally equivalent support group. MAIN OUTCOME MEASURES: Brain Injury Coping Skills Questionnaire (PSE), Brief Symptom Inventory-18 ([BSI-18]; emotional distress), and Frontal Systems Behavior Scale (neurobehavioral functions). RESULTS: There were no significant differences between survivors and caregivers on the Brain Injury Coping Skills Questionnaire and BSI-18; therefore, groups were combined during final analyses. Frontal Systems Behavior Scale caregiver data were used for analysis. Both groups showed significantly improved PSE between baseline and follow-up on repeated-measures analysis of variance, with the CBT group showing greater stabilization of change. There was no significant group by time interaction on measures of neurobehavioral functions, but the CBT group showed significant improvements at 3-month follow-up. No significant effects were found on the BSI-18. CONCLUSIONS: To our knowledge, no studies to date have been published comparing a CBT intervention with a support group in a BI population with caregiver participation. This study showed that given equivalent group structure, individuals with BI and caregivers may benefit from either type of intervention in enhancing PSE or maintaining emotional stability. However, there was a trend for individuals who received CBT to maintain the effects of improved PSE, whereas support group participants showed a trend for decline. This study offers a new conceptualization that with certain group dynamics and support, individuals with BI and caregivers may benefit similarly from either a support group or CBT intervention. However, because our sample did not include individuals in clinically significant emotional distress, we cannot rule out the possibility that those with more significant challenges in PSE or emotional functions may show greater benefits with a CBT group. PMID- 26551232 TI - Nonequilibrium-Plasma-Synthesized ZnO Nanocrystals with Plasmon Resonance Tunable via Al Doping and Quantum Confinement. AB - Metal oxide semiconductor nanocrystals (NCs) exhibit localized surface plasmon resonances (LSPRs) tunable within the infrared (IR) region of the electromagnetic spectrum by vacancy or impurity doping. Although a variety of these NCs have been produced using colloidal synthesis methods, incorporation and activation of dopants in the liquid phase has often been challenging. Herein, using Al-doped ZnO (AZO) NCs as an example, we demonstrate the potential of nonthermal plasma synthesis as an alternative strategy for the production of doped metal oxide NCs. Exploiting unique, thoroughly nonequilibrium synthesis conditions, we obtain NCs in which dopants are not segregated to the NC surfaces and local doping levels are high near the NC centers. Thus, we achieve overall doping levels as high as 2 * 10(20) cm(-3) in NCs with diameters ranging from 12.6 to 3.6 nm, and for the first time experimentally demonstrate a clear quantum confinement blue shift of the LSPR energy in vacancy- and impurity-doped semiconductor NCs. We propose that doping of central cores and heavy doping of small NCs are achievable via nonthermal plasma synthesis, because chemical potential differences between dopant and host atoms-which hinder dopant incorporation in colloidal synthesis are irrelevant when NC nucleation and growth proceed via irreversible interactions among highly reactive gas-phase ions and radicals and ligand-free NC surfaces. We explore how the distinctive nucleation and growth kinetics occurring in the plasma influences dopant distribution and activation, defect structure, and impurity phase formation. PMID- 26551231 TI - Tomato MBD5, a methyl CpG binding domain protein, physically interacting with UV damaged DNA binding protein-1, functions in multiple processes. AB - In tomato (Solanum lycopersicum), high pigment mutations (hp-1 and hp-2) were mapped to genes encoding UV-damaged DNA binding protein 1 (DDB1) and de-etiolated 1 (DET1), respectively. Here we characterized a tomato methyl-CpG-binding domain protein SlMBD5 identified by yeast two-hybrid screening using SlDDB1 as a bait. Yeast two-hybrid assay demonstrated that the physical interaction of SlMBD5 with SlDDB1 is mediated by the C-termini of SlMBD5 and the beta-propeller-C (BPC) of SlDDB1. Co-immunoprecipitation analyses revealed that SlMBD5 associates with SlDDB1-interacting partners including SlDET1, SlCUL4, SlRBX1a and SlRBX1b in vivo. SlMBD5 was shown to target to nucleus and dimerizes via its MBD motif. Electrophoresis mobility shift analysis suggested that the MBD of SlMBD5 specifically binds to methylated CpG dinucleotides but not to methylated CpHpG or CpHpH dinucleotides. SlMBD5 expressed in protoplast is capable of activating transcription of CG islands, whereas CUL4/DDB1 antagonizes this effect. Overexpressing SlMBD5 resulted in diverse developmental alterations including darker green fruits with increased plastid level and elevated pigmentation, as well as enhanced expression of SlGLK2, a key regulator of plastid biogenesis. Taken together, we hypothesize that the physical interaction of SlMBD5 with the CUL4-DDB1-DET1 complex component may affect its binding activity to methylated DNA and subsequently attenuate its transcription activation of downstream genes. PMID- 26551233 TI - Administration of Ferric Citrate Hydrate Decreases Circulating FGF23 Levels Independently of Serum Phosphate Levels in Hemodialysis Patients with Iron Deficiency. AB - BACKGROUND/AIM: Dietary phosphate intake and vitamin D receptor activator (VDRA) regulate fibroblast growth factor 23 (FGF23); iron may modulate FGF23 metabolism. We aimed to determine whether oral iron supplementation influences serum FGF23 concentration in hemodialysis (HD) patients, while excluding the effect of dietary phosphate intake. METHODS: This prospective study enrolled 27 maintenance HD patients with iron deficiency and hyperphosphatemia treated with sevelamer HCl. The phosphate binder was changed from sevelamer-HCl to ferric citrate hydrate (FCH) to maintain constant phosphate levels. VDRA, other phosphate binders, and cinacalcet HCl were not changed. Serum intact FGF23, C-terminal FGF23 (C-term FGF23), intact parathyroid hormone (PTH), 1,25(OH)2D and other parameters were monitored for 12 weeks. RESULTS: Serum phosphate levels (5.89 +/- 1.45 mg/dl at baseline, 5.54 +/- 1.35 mg/dl at 12 weeks) and 1,25(OH)2D levels were unchanged. Serum ferritin levels increased from 25.6 +/- 24.3 ng/ml at baseline to 55.8 +/- 33.5 ng/ml at 12 weeks with FCH administration. Serum intact FGF23 and C-term FGF23 levels significantly decreased at 12 weeks compared with baseline (2,000 (1,300.0-3,471.4) to 1,771.4 (1,142.9-2,342.9) pg/ml, p = 0.01, and 1,608.7 (634.8-2,308.7) to 1,165.2 (626.1-1,547.8) RU/ml, p = 0.007, respectively); serum intact PTH levels significantly increased (96 (65-125) to 173 (114-283) pg/ml, p < 0.001). CONCLUSIONS: Oral FCH administration decreased serum intact FGF23 and C-term FGF23 levels and increased intact PTH levels; phosphate and 1,25(OH)2D levels were unchanged. Oral FCH administration to treat iron deficiency is a possible strategy for reducing serum FGF23 levels independent of phosphate and VDRA. PMID- 26551234 TI - Effectiveness of Endoluminal Vacuum-assisted Closure Therapy (Endosponge) for the Treatment of Pelvic Anastomotic Leakage After Colorectal Surgery. AB - Anastomotic leakage is a serious complication with significant morbidity and mortality. The popularity of endoscopic treatment (Endo-SPONGE) is increasing for distally located colorectal pouch-anal anastomotic leakages. This was a retrospective study of 15 cases involving the application of the Endo-SPONGE for anastomotic leakage following proctectomy between May 2009 and May 2014. Of the 15 cases, lower anterior resection occurred in 12 cases (80%), and pouch-anal anastomosis in 3 cases (18%). In 8 patients (55%), the endosponge was applied during the early term, and in 7 patients (45%) during the late term. The average number of applications was 2.2 (range, 1 to 5). Treatment was discontinued due to the progression of pelvic sepsis in 2 patients and due to bleeding in 1 patient. Lumen integrity was achieved in 12 cases. Lumen integrity after anastomotic leakages can be preserved by endoluminal vacuum therapy, which permits the closure of the stoma without requiring reconstructive surgery. PMID- 26551235 TI - Laparoscopic Cecostomy Tube Placement. AB - Fecal incontinence is a debilitating problem for many children, especially those with anorectal malformations. Historically, surgical options have included the Malone antegrade continence enema, using an appendicostomy for antegrade colonic enemas. Since the development of this procedure, multiple alternatives have been developed, including the Chait cecostomy tube. Here, we present our technique for laparoscopic cecostomy tube placement. We find that this approach has several advantages, including mobilization of the cecum to allow the tube to be placed below the waistline for optimal cosmesis and comfort, increased safety provided by direct vision of needle access to the cecum, and increased security of the cecum to the abdominal wall allowing for safer tube replacement should it become dislodged in the early postoperative period. PMID- 26551236 TI - Endoscopic Web Localization for Laparoscopic Duodenal Web Excision. AB - When performing an open duodenal web excision, it is helpful to identify the web using a nasogastric tube because it is often difficult to determine where the web origin is located when looking at the serosal side of the bowel. However, it may be challenging to navigate the nasogastric tube to the web during laparoscopy. We present a novel technique that utilizes intraoperative endoscopy to precisely identify the location of the duodenal web, facilitating laparoscopic excision. Intraoperative endoscopy was implemented in the case of a 3-month-old boy undergoing laparoscopic excision of a duodenal web. With endoscopic visualization and transillumination, the duodenal web was precisely identified and excised laparoscopically. A supplemental video of the case presentation and technique is provided in the online version of this manuscript (Supplemental Digital Content 1, http://links.lww.com/SLE/A134). The procedure was completed successfully and the patient did well postoperatively. Flexible endoscopy is a useful adjunct for duodenal web localization during laparoscopy, improving on the previous method of estimating the location based on a change in duodenal caliber. PMID- 26551237 TI - Comparative analysis of the mechanisms of sulfur anion oxidation and reduction by dsr operon to maintain environmental sulfur balance. AB - Sulfur metabolism is one of the oldest known redox geochemical cycles in our atmosphere. These redox processes utilize different sulfur anions and the reactions are performed by the gene products of dsr operon from phylogenetically diverse sets of microorganisms. The operon is involved in the maintenance of environmental sulfur balance. Interestingly, the dsr operon is found to be present in both sulfur anion oxidizing and reducing microorganisms and in both types of organisms DsrAB protein complex plays a vital role. Though there are various reports regarding the genetics of dsr operon there are practically no reports dealing with the structural aspects of sulfur metabolism by dsr operon. In our present study, we tried to compare the mechanisms of sulfur anion oxidation and reduction by Allochromatium vinosum and Desulfovibrio vulgaris respectively through DsrAB protein complex. We analyzed the modes of bindings of sulfur anions to the DsrAB protein complex and observed that for sulfur anion oxidizers, sulfide and thiosulfate are the best substrates whereas for reducers sulfate and sulfite have the best binding abilities. We analyzed the binding interaction pattern of the DsrA and DsrB proteins while forming the DsrAB protein complexes in Desulfovibrio vulgaris and Allochromatium vinosum. To our knowledge this is the first report that analyzes the differences in binding patterns of sulfur substrates with DsrAB protein from these two microorganisms. This study would therefore be essential to predict the biochemical mechanism of sulfur anion oxidation and reduction by these two microorganisms i.e., Desulfovibrio vulgaris (sulfur anion reducer) and Allochromatium vinosum (sulfur anion oxidizer). Our observations also highlight the mechanism of sulfur geochemical cycle which has important implications in future study of sulfur metabolism as it has a huge application in waste remediation and production of industrial bio-products viz. vitamins, bio-polyesters and bio-hydrogen. PMID- 26551238 TI - Neuroethical implications of deep brain stimulation in degenerative disorders. AB - PURPOSE OF REVIEW: The use of deep brain stimulation (DBS) in degenerative diseases involving cognitive impairment raises important ethical issues. This review takes into account the previous publications on the ethical issues of DBS to re-evaluate this technique in the framework of cognitive degenerative diseases, especially Alzheimer's disease and dementia associated to Parkinson's disease. RECENT FINDINGS: The serendipitous discovery of the properties of DBS in memory enhancement fostered the expectations of the patients, the experts, and the industry involved in the production of the devices. Nonetheless, there is still a lack of evidence of its effectiveness in slowing or stopping the evolution of the initial cognitive decline into dementia, and a lack of a cognitive model to explain its effects on the memory circuit. SUMMARY: Applying the principles for the ethical assessment of new treatments in biomedicine to the use of DBS in cognitive impairment and especially in memory loss, we conclude that any use of this technique for this indication should be reserved to experimental settings, with clear protocols and strict inclusion criteria for the selection of the possible candidates for surgery. PMID- 26551239 TI - Tumor treating fields: a new standard treatment for glioblastoma? AB - PURPOSE OF REVIEW: Tumor treating fields (TTFields), an external therapeutic device with antimitotic properties, is a Food and Drug Administration approved treatment for recurrent glioblastoma (GBM) that has been reported to be efficacious in newly diagnosed GBM as well. RECENT FINDINGS: Preclinical data show that TTFields is an antimitotic agent that additionally augments response to alkylator-based chemotherapy. In a single study, nearly 15% of recurrent GBM treated with TTFields alone display durable responses. Responses may be delayed, sometimes after an initial progression, and are highly correlated to treatment compliance and to survival. In newly diagnosed GBM, a preplanned interim analysis of the phase III randomized trial (standard of care with or without TTFields) showed a statistically significant effect of TTFields resulting in a net gain of 3 months in both progression-free and overall survival. SUMMARY: TTFields is a novel noninvasive therapeutic option for recurrent GBM. The role of TTFields in newly diagnosed GBM will be adjudicated pending publication of the final results of the randomized EF-14 trial. If these results are compelling, this may result in accelerated approval and potentially a new standard of care for newly diagnosed GBM. PMID- 26551241 TI - PCR-mediated gene modification strategy for construction of fluorescent protein fusions in Candida parapsilosis. AB - Candida parapsilosis is a common cause of invasive candidiasis, especially in premature infants, even surpassing Candida albicans as the most frequently identified Candida species in some newborn intensive care units. Whereas many molecular tools are available to facilitate the study of C. albicans, relatively few have been developed for C. parapsilosis. In this study, we show that plasmids harbouring green, yellow and mCherry fluorescent protein sequences, previously developed for expression in C. albicans, can be used to construct fluorescent fusion proteins in C. parapsilosis by PCR-mediated gene modification. Further, the strategy can be used in clinical isolates of C. parapsilosis, which are typically prototrophic, because the plasmids include NAT1, a dominant selectable trait that confers resistance to the antibiotic nourseothricin. Overall, these tools will be useful to yeast researchers who require the ability to visualize C. parapsilosis directly, e.g. in in vitro and in vivo infection models. In addition, this strategy can be used to generate fluorescence in other C. parapsilosis clinical isolates and to tag sequences of interest for protein localization studies. Lastly, the ability to express up to three different fluorescent proteins will allow researchers to visualize and differentiate C. parapsilosis and/or C. albicans clinical isolates from each other in mixed infection models. PMID- 26551242 TI - Silicone Gel Breast Implants: What We Know About Safety After All These Years. PMID- 26551244 TI - Explosive generalization of nodular vasculitis - Mycobacterium marinum challenges the paradigm. PMID- 26551243 TI - Physicochemical Properties of Starch Isolated from Bracken (Pteridium aquilinim) Rhizome. AB - Bracken (Pteridium aquilinum) is an important wild plant starch resource worldwide. In this work, starch was separated from bracken rhizome, and the physicochemical properties of this starch were systematically investigated and compared with 2 other common starches, that is, starches from waxy maize and potato. There were significant differences in shape, birefringence patterns, size distribution, and amylose content between bracken and the 2 other starches. X-ray diffraction analysis revealed that bracken starch exhibited a typical C-type crystalline structure. Bracken starch presented, respectively, lower and higher relative degree of crystallinity than waxy maize and potato starches. Ordered structures in particle surface differed among these 3 starches. The swelling power tendency of bracken starch in different temperature intervals was very similar to that of potato starch. The viscosity parameters during gelatinization were the lowest in waxy maize, followed by bracken and potato starches. The contents of 3 nutritional components, that is, rapidly digestible, slowly digestible, and resistant starches in native, gelatinized, and retrograded starch from bracken rhizome presented more similarities with potato starch than waxy maize starch. These finding indicated that physicochemical properties of bracken starch showed more similarities with potato starch than waxy maize starch. PMID- 26551245 TI - Two new abietane diterpenoid glycosides from Clinopodium chinense. AB - Two new abietane diterpenoid glycosides, named clinopoditerpenes B (1) and C (2), were isolated from Clinopodium chinese. The structures of the new compounds were determined on the basis of extensive spectral analysis. Compound 1 exhibited cardioprotective effect against H2O2-induced apoptosis in H9c2 cells. PMID- 26551246 TI - Influence of Copper Oxidation State on the Bonding and Electronic Structure of Cobalt-Copper Complexes. AB - Heterobimetallic complexes that pair cobalt and copper were synthesized and characterized by a suite of physical methods, including X-ray diffraction, X-ray anomalous scattering, cyclic voltammetry, magnetometry, electronic absorption spectroscopy, electron paramagnetic resonance, and quantum chemical methods. Both Cu(II) and Cu(I) reagents were independently added to a Co(II) metalloligand to provide (py3tren)CoCuCl (1-Cl) and (py3tren)CoCu(CH3CN) (2-CH3CN), respectively, where py3tren is the triply deprotonated form of N,N,N-tris(2-(2 pyridylamino)ethyl)amine. Complex 2-CH3CN can lose the acetonitrile ligand to generate a coordination polymer consistent with the formula "(py3tren)CoCu" (2). One-electron chemical oxidation of 2-CH3CN with AgOTf generated (py3tren)CoCuOTf (1-OTf). The Cu(II)/Cu(I) redox couple for 1-OTf and 2-CH3CN is reversible at 0.56 and -0.33 V vs Fc(+)/Fc, respectively. The copper oxidation state impacts the electronic structure of the heterobimetallic core, as well as the nature of the Co-Cu interaction. Quantum chemical calculations showed modest electron delocalization in the (CoCu)(+4) state via a Co-Cu sigma bond that is weakened by partial population of the Co-Cu sigma antibonding orbital. By contrast, no covalent Co-Cu bonding is predicted for the (CoCu)(+3) analogue, and the d electrons are fully localized at individual metals. PMID- 26551247 TI - Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and Bayesian phylogenetic analysis to characterize Candida clinical isolates. AB - Clinical Candida isolates from two different hospitals in Rome were identified and clustered by MALDI-TOF MS system and their origin and evolution estimated by Bayesian phylogenetic analysis. The different species of Candida were correctly identified and clustered separately, confirming the ability of these techniques to discriminate between different Candida species. Focusing MALDI-TOF analysis on a single Candida species, Candida albicans and Candida parapsilosis strains clustered differently for hospital setting as well as for period of isolation than Candida glabrata and Candida tropicalis isolates. The evolutionary rates of C. albicans and C. parapsilosis (1.93*10(-2) and 1.17*10( 2)substitutions/site/year, respectively) were in agreement with a higher rate of mutation of these species, even in a narrow period, than what was observed in C. glabrata and C. tropicalis strains (6.99*10(-4) and 7.52*10( 3)substitutions/site/year, respectively). C. albicans resulted as the species with the highest between and within clades genetic distance values in agreement with the temporal-related clustering found by MALDI-TOF and the high evolutionary rate 1.93*10(-2)substitutions/site/year. PMID- 26551249 TI - Control of I-V hysteresis in CH3NH3PbI3 perovskite solar cell. AB - Mismatch of current (I)-voltage (V) curves with respect to the scan direction, so called I-V hysteresis, raises critical issue in MAPbI3 (MA = CH3NH3) perovskite solar cell. Although ferroelectric and ion migration have been proposed as a basis for the hysteresis, origin of hysteresis has not been apparently unraveled. We report here on the origin of I-V hysteresis of perovskite solar cell that was systematically evaluated by the interface-dependent electrode polarizations. Frequency (f)-dependent capacitance (C) revealed that the normal planar structure with the TiO2/MAPbI3/spiro-MeOTAD configuration showed most significant I-V hysteresis along with highest capacitance (10(-2) F/cm(2)) among the studied cell configurations. Substantial reduction in capacitance to 10(-3) F/cm(2) was observed upon replacing TiO2 with PCBM, indicative of the TiO2 layer being mainly responsible for the hysteresis. The capacitance was intensively reduced to 10(-5) F/cm(2) and C-f feature shifted to higher frequency for the hysteresis-free planar structures with combination of PEDOT: PSS, NiO, and PCBM, which underlines the spiro-MeOTAD in part contributes to the hysteresis. This work is expected to provide a key to the solution of the problem on I-V hysteresis in perovskite solar cell. PMID- 26551248 TI - Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A Novel Antimycobacterial Class Targeting Mycobacterial Respiration. AB - High-throughput screening of a library of small polar molecules against Mycobacterium tuberculosis led to the identification of a phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing the ester moiety with a methyl oxadiazole bioisostere. A route utilizing polymer supported reagents was designed and executed to explore structure-activity relationships with respect to the N-benzyl substituent, leading to compounds with nanomolar activity. The frontrunner compound (5h) from these studies was well tolerated in mice. A M. tuberculosis cytochrome bd oxidase deletion mutant (DeltacydKO) was hyper-susceptible to compounds from this series, and a strain carrying a single point mutation in qcrB, the gene encoding a subunit of the menaquinol cytochrome c oxidoreductase, was resistant to compounds in this series. In combination, these observations indicate that this novel class of antimycobacterial compounds inhibits the cytochrome bc1 complex, a validated drug target in M. tuberculosis. PMID- 26551250 TI - Correction to ametoctradin is a potent qo site inhibitor of the mitochondrial respiration complex III. PMID- 26551251 TI - The Contributions of Segmental and Suprasegmental Information in Reading Chinese Characters Aloud. AB - The Chinese writing system provides an excellent case for testing the contribution of segmental and suprasegmental information in reading words aloud within the same language. In logographic Chinese characters, neither segmental nor tonal information is explicitly represented, whereas in Pinyin, an alphabetic transcription of the character, both are explicitly represented. Two primed naming experiments were conducted in which the targets were always written characters. When logographic characters served as the primes (Experiment 1), syllable segmental and tonal information appeared to be represented and encoded as an integral unit which in turn facilitated target character naming. When Pinyin served as the primes (Experiment 2), the explicit phonetic representation facilitated encoding of both segmental and suprasegmental information, but with later access to suprasegmental information. In addition, Chinese speakers were faster to name characters than Pinyin in a simple naming task (Experiment 3), suggesting that Pinyin may be read via a phonological assembly route, whereas characters may be read via a lexical route. Taken together, our findings point to the need to consider the contributions of both segmental and suprasegmental information and the time course in the well-established models for reading aloud, as well as the cognitive mechanisms underlying the reading aloud of logographic characters versus alphabetic Pinyin script. PMID- 26551252 TI - School engagement, acculturation, and mental health among migrant adolescents in Israel. AB - This study aimed to explore the role of school engagement and the mediation effect of acculturation in predicting 1.5 and second-generation migrant adolescents' mental health and risk behaviors. Participants included 448 seventh to tenth grade Israeli students (mean age 14.50, 53% boys): 128 non-Jewish 1.5 generation migrant adolescents (children of migrants living in Israel), 118 second-generation migrants (children of migrants born and living in Israel), and an age-matched sample of 202 native-born Jewish adolescents. All participants completed a battery of questionnaires assessing mental health symptoms, engagement in risk behaviors, social adjustment, and school engagement. Both migrant adolescent groups also completed an acculturation questionnaire. Differences between groups in school engagement, mental health symptoms, and risk behavior were examined, and structural equation modeling (SEM) was used to investigate the hypothesized mediating effect of acculturation. Findings revealed substantially higher levels of mental health symptoms (p < .001) and risk behaviors (p = .001) among 1.5 and second-generation migrant adolescents compared with native-born adolescents, with no significant differences between 1.5 generation and second-generation migrants. Migrants' age and gender were associated with mental health symptoms and risk behaviors-older participants engaged in more risk behaviors (p = .02), and females had elevated mental health symptoms (p = .007). Identification with the host country mediated the relationships between school engagement and mental health symptoms (ps .006 and .008) and risk behaviors (ps .001 and .004) in 1.5 generation and second generation migrants, respectively. The results are discussed in reference to current theories and research, as well as practical implications for prevention and intervention. (PsycINFO Database Record PMID- 26551253 TI - Latino immigration: Preparing school psychologists to meet students' needs. AB - As the population of immigrant Latino students continues to rise, school psychologists serving Latino children and families must develop the knowledge and skills necessary to provide high-quality psychological services to culturally and linguistically diverse students from immigrant families. Following a review of the relevant literature on the educational, social, and emotional needs of immigrant Latino children, we describe Project SUPERB (Scholars Using Psychology and Education to Reach Bilinguals), a grant-funded initiative to address the shortage of bilingual (Spanish-English) school psychologists. We discuss important issues regarding training and preparation to develop the competencies necessary for effective assessment, intervention, and collaboration in the context of school settings to help immigrant children achieve success. Finally, we identify ways in which school psychologists may adopt a leadership role in working with schools and families to promote positive outcomes. (PsycINFO Database Record PMID- 26551254 TI - Understanding the relationship between inattention and early literacy trajectories in kindergarten. AB - The purpose of this study was to examine the relationship between inattention, academic enabling behaviors (i.e., motivation, engagement, and interpersonal skills), and early literacy outcomes. Kindergarten students (N = 181; 55.2% male; 62% white) from two research sites (Southeastern U.S. and Eastern Canada) were assessed using the Letter Naming and Letter Sound Fluency AIMSweb Tests of Early Literacy (Shinn & Shinn, 2012) at three points across the school year. Their teachers provided information on the level of attention-deficit/hyperactivity disorder symptoms (ADHD Symptom Checklist-4; Gadow & Sprafkin, 2008) and academic enabling behaviors (Academic Competence Evaluation Scales; DiPerna & Elliott, 2000). Structural equation modeling (SEM) was used to determine predictors of initial level and growth in early literacy. Specifically, a series of models were tested to determine if a multidimensional model of academic enablers (AEs) mediated the relationship. Engagement predicted students' initial levels of early literacy, suggesting that this is an important mediator to consider between inattention and early literacy skills. Motivation related positively to engagement. Inattention also predicted both motivation and interpersonal skills in the negative direction. These findings suggest that AEs play an important role in the relationship between inattention and early literacy. AEs provide malleable targets for intervention and should be considered when developing intervention for youth at risk for academic failure. (PsycINFO Database Record PMID- 26551256 TI - Generalized acute subcutaneous edema as a rare cutaneous manifestation of severe dermatomyositis. PMID- 26551255 TI - miR-599 Inhibits Vascular Smooth Muscle Cells Proliferation and Migration by Targeting TGFB2. AB - Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of cardiovascular diseases including coronary heart disease, restenosis and atherosclerosis. MicroRNAs are a class of small, non-coding and endogenous RNAs that play critical roles in VSMCs function. In this study, we showed that PDGF-bb, as a stimulant, promoted VSMCs proliferation and suppressed the expression of miR-599. Moreover, overexpression of miR-599 inhibited VSMCs proliferation and also suppressed the PCNA and ki-67 expression. In addition, we demonstrated that ectopic expression of miR-599 repressed the VSMCs migration. We also showed that miR-599 inhibited type I collagen, type V collagen and proteoglycan expression. Furthermore, we identified TGFb2 as a direct target gene of miR-599 in VSMCs. Overexpression of TGFb2 reversed miR-599 induced inhibition of VSMCs proliferation and type I collagen, type V collagen and proteoglycan expression. In conclusion, our findings suggest miR-599 plays a crucial role in controlling VSMCs proliferation and matrix gene expression by regulating TGFb2 expression. PMID- 26551257 TI - Spleen preservation versus splenectomy in laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer: A comparison of short-term outcomes. AB - INTRODUCTION: Splenic hilar lymph node dissection via a splenectomy for advanced proximal gastric cancer remains controversial. Recently, a laparoscopic spleen preserving hilar lymph node dissection procedure was described in several publications. To assess the feasibility and safety of spleen-preserving laparoscopic total gastrectomy with D2 lymphadenectomy (LTG-D2), the present retrospective study compared the short-term surgical outcomes between spleen preservation and splenectomy during laparoscopic D2 total gastrectomy (LTG-D2S). METHOD: This study included 59 patients who underwent LTG-D2 and 19 patients who underwent LTG-D2S. RESULTS: The mean operation time did not significantly differ between the LTG-D2 and LTG-D2S groups (339.4 +/- 56.8 vs 356.8 +/- 46.0 min). The mean blood loss tended to be smaller in the LTG-D2 group than in the LTG-D2S group (105.9 +/- 89.7 vs 210.0 +/- 149.5 mL). The mean number of retrieved lymph nodes did not significantly differ between the LTG-D2 and LTG-D2S groups (39.9 +/ 17.0 vs 40.6 +/- 14.9), and the mean number of retrieved lymph nodes at the splenic hilum also did not significantly differ between the LTG-D2 and LTG-D2S groups (1.3 +/- 1.7 vs 2.4 +/- 2.6). Mild pancreatic fistula occurred in three cases (5%) in the LTG-D2 group and in three cases (15.8%) in the LTG-D2S group. CONCLUSION: A LTG-D2 is feasible in terms of the short-term outcomes. However, the indications for this complicated procedure should be considered carefully. PMID- 26551258 TI - Efficacy and Feasibility of Salvage Living Donor Liver Transplantation after Initial Liver Resection in Patients with Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: Liver transplantation (LT) is promising method of treatment for hepatocellular carcinoma (HCC) patients, but is limited by donor organ shortages and tumor progression during long wait periods. This study investigated the efficacy of salvage living donor LT (LDLT) after initial liver resection (LR) in HCC patients. METHODS: Sixty patients with HCC who underwent primary LDLT (n = 45) or salvage LDLT after initial LR (n = 15) were enrolled. Significant prognostic variables determined by univariate analysis were subjected to multivariate analysis using a Cox proportional hazard regression model. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were used to adjust for selection bias between groups. RESULTS: The salvage group had significantly higher Child-Pugh class A (p = 0.003), >=3 pretransplant treatments (p = 0.007), and reoperation rates for postoperative bleeding (p = 0.032) than the primary LDLT group, whereas overall and recurrence-free survival rates were comparable. After IPTW matching, the salvage LDLT group had significantly more reoperations for postoperative bleeding (hazard ratio 7.948, p = 0.017). CONCLUSIONS: First-line LR followed by salvage LDLT allows survival equal to that of primary LDLT. Salvage LDLT following primary LR could be an effective therapy. PMID- 26551259 TI - Patterns of Institutional Review of Percutaneous Coronary Intervention Appropriateness and the Effect on Quality of Care and Clinical Outcomes. PMID- 26551260 TI - Don't throw the baby out with the bathwater: Depressive traits are part and parcel of neuroticism. PMID- 26551262 TI - Leachate/domestic wastewater aerobic co-treatment: A pilot-scale study using multivariate analysis. AB - Multivariate analysis was used to identify the variables affecting the performance of pilot-scale activated sludge (AS) reactors treating old leachate from a landfill and from domestic wastewater. Raw leachate was pre-treated using air stripping to partially remove the total ammoniacal nitrogen (TAN). The control AS reactor (AS-0%) was loaded only with domestic wastewater, whereas the other reactor was loaded with mixtures containing leachate at volumetric ratios of 2 and 5%. The best removal efficiencies were obtained for a ratio of 2%, as follows: 70 +/- 4% for total suspended solids (TSS), 70 +/- 3% for soluble chemical oxygen demand (SCOD), 70 +/- 4% for dissolved organic carbon (DOC), and 51 +/- 9% for the leachate slowly biodegradable organic matter (SBOM). Fourier transform infrared (FTIR) spectroscopic analysis confirmed that most of the SBOM was removed by partial biodegradation rather than dilution or adsorption of organics in the sludge. Nitrification was approximately 80% in the AS-0% and AS 2% reactors. No significant accumulation of heavy metals was observed for any of the tested volumetric ratios. Principal component analysis (PCA) and partial least squares (PLS) indicated that the data dimension could be reduced and that TAN, SCOD, DOC and nitrification efficiency were the main variables that affected the performance of the AS reactors. PMID- 26551261 TI - Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis. AB - Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer's Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic organization of the optic radiation including a successful reconstruction of Meyer's loop. Then, using the reconstructed optic radiation bundle from the HCP cohort, we construct a probabilistic atlas and demonstrate its consistency with a post-mortem atlas. Finally, we generate a shape-based representation of the optic radiation for morphometry analysis. PMID- 26551263 TI - Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. AB - BACKGROUND: Effective treatment options are needed for patients with genotype 1 or 3 hepatitis C virus (HCV) infection in whom previous therapy has failed. OBJECTIVE: To assess the efficacy and safety of sofosbuvir plus velpatasvir, with and without ribavirin, in treatment-experienced patients. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01909804). SETTING: 58 sites in Australia, New Zealand, and the United States. PATIENTS: Treatment-experienced adults with genotype 3 HCV infection without cirrhosis (cohort 1) and with compensated cirrhosis (cohort 2) and patients with genotype 1 HCV infection that was unsuccessfully treated with a protease inhibitor with peginterferon and ribavirin (50% could have compensated cirrhosis) (cohort 3). INTERVENTION: All patients received 12 weeks of treatment that included 400 mg of sofosbuvir once daily. Patients in each cohort were randomly assigned to 25 mg of velpatasvir once daily with or without ribavirin or 100 mg of velpatasvir once daily with or without ribavirin. MEASUREMENTS: Proportion of patients with sustained virologic response at week 12 after treatment (SVR12). RESULTS: In cohort 1, SVR12 rates were 85% with 25 mg of velpatasvir, 96% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 100% with 100 mg of velpatasvir plus ribavirin. In cohort 2, SVR12 rates were 58% with 25 mg of velpatasvir, 84% with 25 mg of velpatasvir plus ribavirin, 88% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. In cohort 3, SVR12 rates were 100% with 25 mg of velpatasvir, 97% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. The most common adverse events were headache, fatigue, and nausea. LIMITATION: Treatment assignments were not blinded, and no inferential statistics were planned. CONCLUSION: Treatment with 400 mg of sofosbuvir plus 100 mg of velpatasvir for 12 weeks was well-tolerated and highly effective in treatment-experienced patients with genotype 1 or 3 HCV infection. PRIMARY FUNDING SOURCE: Gilead Sciences. PMID- 26551264 TI - Epidemiology of Melanocytic Naevi in Children from Lleida, Catalonia, Spain: Protective Role of Sunscreen in the Development of Acquired Moles. AB - The worldwide incidence of malignant melanoma is increasing. The number of pigmented naevi and amount of solar exposure are important risk factors. The aim of this study was to characterize a paediatric population (from Lleida, Catalonia, Spain) in terms of phenotype, sun behaviour and naevi prevalence. Data on the numbers and distributions of acquired naevi in 369 children, aged 4, 8 and 14 years, were collected and correlated with age, sex, skin phototype and environmental factors (annual/lifetime intermittent and chronic sun exposure, sunburns and sunscreen use). The density of naevi increased with age. Boys had more naevi on the trunk and girls had more naevi on the legs. Children with light skin phototype had more naevi. A higher level of accumulated sun exposure correlated with a higher number of naevi in children with non-adequate sunscreen use. In conclusion, several risk factors associated with naevi density and distribution were found, as previously reported by others. Multivariate analysis confirmed a protective role of sunscreen in the development of acquired melanocytic naevi. PMID- 26551265 TI - The relation between stress and alcohol use among Hispanic adolescents. AB - We explored the relation between 8 domains of Hispanic stress and alcohol use and frequency of use in a sample of Hispanic adolescents between 11 and 19 years old (N = 901). Independent t tests were used to compare means of domains of Hispanic stress between adolescents who reported alcohol use and those who reported no use. In addition, multinomial logistic regression was used to examine whether domains of Hispanic stress were related to alcohol use and whether the relation differed by gender and age. Multiple imputation was used to address missing data. In the analytic sample, 75.8% (n = 683) reported no use and 24.2% (n = 218) reported alcohol use during the previous 30 days. Higher mean Hispanic stress scores were observed among youths who reported alcohol use during the previous 30 days in 5 domains: acculturation gap, community and gang violence, family economic, discrimination, and family and drug-related stress. Increased community and gang violence, family and drug, and acculturative gap stress were found to be associated with some alcohol use categories beyond the effect of other domains. Few differences in the association between Hispanic stress and alcohol use by gender and age were observed. Study findings indicate that family and drug related, community and gang violence, and acculturative gap stress domains are salient factors related to alcohol use among Hispanic adolescents, and their implications for prevention science are discussed. PMID- 26551266 TI - Development and psychometric properties of the Smoking Restraint Questionnaire. AB - Restraint is a component of self-control that focuses on the deliberate reduction of an undesired behavior and is theorized to play a role in smoking reduction and cessation. However, there exists no instrument to assess smoking restraint. This research aimed to develop the Smoking Restraint Questionnaire (SRQ) to meet this need. Participants were 406 smokers (48% female; 52.2% nondaily) with a mean age of 38.83 years (SD = 12.05). They completed a baseline questionnaire designed to assess smoking restraint. They also completed 21 days of ecological momentary assessment (EMA), during which they recorded each cigarette smoked and answered questions related to planned restraint every morning, and restraint attempts every evening. The 4-item questionnaire of smoking restraint was found to fit a single factor (root mean square error of approximation = .038, comparative fit index = .99, Tucker-Lewis index = .99), and the resulting composite was reliable (composite reliability = 0.74). The questionnaire contains items that assess the setting of weekly restraint goals and attempts at not lighting up when tempted to smoke. Participant SRQ scores positively correlated with EMA data on plans to restrain (p < .001) and frequency of restraint attempts (p < .001). These correlations suggest that the SRQ has good predictive validity in relation to the intention and behaviors of smoking reduction. The SRQ is promising as a measure of smoking restraint and may enable further research and insights into smoking reduction and cessation. PMID- 26551268 TI - The Puerto Rico Healthcare Crisis. AB - The Commonwealth of Puerto Rico is an organized nonincorporated territory of the United States with a population of more than 3.5 million U.S. citizens. The island has been the focus of much recent attention due to the recent default on its debt (estimated at more than $70 billion), high poverty rates, and increasing unemployment. Less attention, however, has been given to the island's healthcare system, which many believe is on the verge of collapsing. Healthcare makes up 20% of the Puerto Rican economy, and this crisis affects reimbursement rates for physicians while promoting the disintegration of the island's healthcare infrastructure. A major contributor relates to a disparity in federal funding provided to support the island's healthcare system when compared with that provided to the states in the mainland and Hawaii. Puerto Rico receives less federal funding for healthcare than the other 50 states and the District of Columbia even though it pays its share of social security and Medicare taxes. To make matters worse, the U.S. Center for Medicaid and Medicare Services is planning soon to implement another 11% cut in Medical Advantage reimbursements. This disparity in support for healthcare is considered responsible for ~$25 billion of Puerto Rico's total debt. The impact of these events on the health of Puerto Ricans in the island cannot be entirely predicted, but the loss of healthcare providers and diminished access to care are a certainty, and quality care will suffer, leading to serious implications for those with chronic medical disorders including respiratory disease. PMID- 26551267 TI - Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length. AB - Conceptualizations of links between stress and cellular aging in childhood suggest that accumulating stress predicts shorter leukocyte telomere length (LTL). At the same time, several models suggest that emotional reactivity to stressors may play a key role in predicting cellular aging. Using intensive repeated measures, we tested whether exposure or emotional "reactivity" to conflict and warmth in the family were related to LTL. Children (N=39; 30 target children and 9 siblings) between 8 and 13 years of age completed daily diary questionnaires for 56 consecutive days assessing daily warmth and conflict in the marital and the parent-child dyad, and daily positive and negative mood. To assess exposure to conflict and warmth, diary scale scores were averaged over the 56 days. Mood "reactivity" was operationalized by using multilevel modeling to generate estimates of the slope of warmth or conflict scores (marital and parent child, separately) predicting same-day mood for each individual child. After diary collection, a blood sample was collected to determine LTL. Among children aged 8-13 years, a stronger association between negative mood and marital conflict, suggesting greater negative mood reactivity to marital conflict, was related to shorter LTL (B=-1.51, p<.01). A stronger association between positive mood and marital affection, suggesting positive mood reactivity, was related to longer LTL (B=1.15, p<.05). These effects were independent of exposure to family and marital conflict and warmth, and positive and negative mood over a two-month period. To our knowledge, these findings, although cross-sectional, represent the first evidence showing that link between children's affective responses and daily family interactions may have implications for telomere length. PMID- 26551270 TI - A novel greenish yellow-orange red Ba3Y4O9:Bi(3+),Eu(3+) phosphor with efficient energy transfer for UV-LEDs. AB - A series of novel color-tunable Ba3Y4O9:Bi(3+),Eu(3+) phosphors were prepared for the first time via the high-temperature solid-state reaction route. The effect of Bi(3+) concentration on the emission intensity of Ba3Y4O9:Bi(3+) was investigated. The emission spectra of the Ba3Y4O9:Bi(3+),Eu(3+) phosphors present both a greenish yellow band of Bi(3+) emission centered at 523 nm, and many characteristic emission lines of Eu(3+), derived from the allowed (3)P1-(1)S0 transition of the Bi(3+) ion and the (5)D0-(7)FJ transition of the Eu(3+) ion, respectively. The energy transfer phenomenon from Bi(3+) to Eu(3+) ions is observed under UV excitation in Bi(3+), Eu(3+) co-doped Ba3Y4O9 phosphors, and their transfer mechanism is demonstrated to be a resonant type via dipole quadrupole interaction. The critical distance between Bi(3+) and Eu(3+) for the energy transfer effect was calculated via the concentration quenching and spectral overlap methods. Results show that color tuning from greenish yellow to orange red can be realized by adjusting the mole ratio of Bi(3+) and Eu(3+) concentrations based on the principle of energy transfer. Moreover, temperature dependent PL properties, CIE chromaticity coordinates and quantum yields of Ba3Y4O9:Bi(3+),Eu(3+) phosphors were also supplied. It is illustrated that the as prepared Ba3Y4O9:Bi(3+),Eu(3+) phosphors can be potential candidates for color tunable phosphors applied in UV-pumped LEDs. PMID- 26551269 TI - Healthcare professionals' views on the mutual consistency of the Finnish Classification of Nursing Interventions and the Oulu Patient Classification. AB - BACKGROUND: Various classification schemes have been used for clinical and administrative purposes, but their concepts have seldom been cross-mapped. Cross mapping is a formal method that can be used for examining existing classifications' validity. AIM: The aim was to cross-map two nursing classifications - the Finnish Classification of Nursing Interventions (FiCNI, version 3.0), developed for structured nursing documentation, and the Oulu Patient Classification (OPCq), created for daily assessment of nursing intensity and evaluate their mutual consistency. The objective was to obtain information on the content equivalence of the two classifications and the consistency of the concepts used, to inform further development of both. METHODS: The Delphi method was utilised, with a panel of experts that included terminology developers, researchers, teachers and nurses (n = 16). Four Delphi rounds were required. In these, panellists selected the most relevant content from the OPCq subareas (n = 6) for each FiCNI main category and subcategory (n = 307). In cases of doubt, respondents were asked to justify their choices. RESULTS: Response rates ranged from 68.8 to 93.8% in the Delphi rounds. After three rounds, 81.4% of the FiCNI categories were cross-mapped with sufficient consensus. A fourth round was needed for 57 FiCNI categories (18.6%). Most FiCNI categories (29.3%) were cross-mapped to the OPCq's subarea 2. Deficiencies in the concepts' clarity and in the OPCq's content areas complicated the cross-mapping. The most unambiguous categories of the FiCNI were found in the respiratory, cardiac and activity components. The components showing greatest ambiguity were skin integrity, mental balance and safety. CONCLUSION: The content and concepts used in both classifications need further development. The cross-mapping results can be utilised for developing reuse of structured nursing data in assessment of nursing intensity and in decision-making in human-resources planning. PMID- 26551271 TI - Regional Shape Control of Strategically Assembled Multishape Memory Vitrimers. AB - Hot-pressing shape memory vitrimers lead to multishape memory, multifunctionality, easy reconfiguration, and the possibility of mass production of arbitrary smart structures. PMID- 26551273 TI - Transient junction anisotropies orient annular cell polarization in the Drosophila airway tubes. AB - In contrast to planes, three-dimensional (3D) structures such as tubes are physically anisotropic. Tubular organs exhibit a striking orientation of landmarks according to the physical anisotropy of the 3D shape, in addition to planar cell polarization. However, the influence of 3D tissue topography on the constituting cells remains underexplored. Here, we identify a regulatory network polarizing cellular biochemistry according to the physical anisotropy of the 3D tube geometry (tube cell polarization) by a genome-wide, tissue-specific RNAi screen. During Drosophila airway remodelling, each apical cellular junction is equipotent to establish perpendicular actomyosin cables, irrespective of the longitudinal or transverse tube axis. A dynamic transverse enrichment of atypical protein kinase C (aPKC) shifts the balance and transiently targets activated small GTPase RhoA, myosin phosphorylation and Rab11 vesicle trafficking to longitudinal junctions. We propose that the PAR complex translates tube physical anisotropy into longitudinal junctional anisotropy, where cell-cell communication aligns the contractile cytoskeleton of neighbouring cells. PMID- 26551275 TI - Wild rufous hummingbirds use local landmarks to return to rewarded locations. AB - Animals may remember an important location with reference to one or more visual landmarks. In the laboratory, birds and mammals often preferentially use landmarks near a goal ("local landmarks") to return to that location at a later date. Although we know very little about how animals in the wild use landmarks to remember locations, mammals in the wild appear to prefer to use distant landmarks to return to rewarded locations. To examine what cues wild birds use when returning to a goal, we trained free-living hummingbirds to search for a reward at a location that was specified by three nearby visual landmarks. Following training we expanded the landmark array to test the extent that the birds relied on the local landmarks to return to the reward. During the test the hummingbirds' search was best explained by the birds having used the experimental landmarks to remember the reward location. How the birds used the landmarks was not clear and seemed to change over the course of each test. These wild hummingbirds, then, can learn locations in reference to nearby visual landmarks. PMID- 26551276 TI - Predicting the long-term durability of hemp-lime renders in inland and coastal areas using Mediterranean, Tropical and Semi-arid climatic simulations. AB - Hemp-based composites are eco-friendly building materials as they improve energy efficiency in buildings and entail low waste production and pollutant emissions during their manufacturing process. Nevertheless, the organic nature of hemp enhances the bio-receptivity of the material, with likely negative consequences for its long-term performance in the building. The main purpose of this study was to study the response at macro- and micro-scale of hemp-lime renders subjected to weathering simulations in an environmental cabinet (one year was condensed in twelve days), so as to predict their long-term durability in coastal and inland areas with Mediterranean, Tropical and Semi-arid climates, also in relation with the lime type used. The simulated climatic conditions caused almost unnoticeable mass, volume and colour changes in hemp-lime renders. No efflorescence or physical breakdown was detected in samples subjected to NaCl, because the salt mainly precipitates on the surface of samples and is washed away by the rain. Although there was no visible microbial colonisation, alkaliphilic fungi (mainly Penicillium and Aspergillus) and bacteria (mainly Bacillus and Micrococcus) were isolated in all samples. Microbial growth and diversification were higher under Tropical climate, due to heavier rainfall. The influence of the bacterial activity on the hardening of samples has also been discussed here and related with the formation and stabilisation of vaterite in hemp-lime mixes. This study has demonstrated that hemp-lime renders show good durability towards a wide range of environmental conditions and factors. However, it might be useful to take some specific preventive and maintenance measures to reduce the bio-receptivity of this material, thus ensuring a longer durability on site. PMID- 26551277 TI - Long-term impact of biochar on the immobilisation of nickel (II) and zinc (II) and the revegetation of a contaminated site. AB - A field remediation treatment was carried out to examine the long-term effect of biochar on the immobilisation of metals and the revegetation of a contaminated site in Castleford, UK. The extracted concentrations of nickel (Ni) (II) and zinc (Zn) (II) in the carbonic acid leaching tests were reduced by 83-98% over three years. The extracted Ni (II) and Zn (II) concentrations three years after the treatment were comparable to a cement-based treatment study carried out in a parallel manner on the same site. The sequential extraction results indicated that biochar addition (0.5-2%) increased the residue fractions of Ni (II) (from 51% to 61-66%) and Zn (II) (from 7% to 27-35%) in the soils through competitive sorption, which may have resulted in the reduction of leachabilities of Ni (II) (from 0.35% to 0.12-0.15%) and Zn (II) (from 0.12% to 0.01%) in the plots with biochar compared with that without biochar three years after the treatment. The germination of grass in the plots on site failed. Further laboratory pot study suggested that larger amounts of biochar (5% or more) and compost (5% or more) were needed for the success of revegetation on this site. This study suggests the effectiveness and potential of biochar application in immobilising heavy metals in contaminated site in the long term. PMID- 26551274 TI - IRE1alpha is an endogenous substrate of endoplasmic-reticulum-associated degradation. AB - Endoplasmic reticulum (ER)-associated degradation (ERAD) represents a principle quality control mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unexplored. Here we discover that IRE1alpha, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. ERAD-mediated IRE1alpha degradation occurs under basal conditions in a BiP dependent manner, requires both the intramembrane hydrophilic residues of IRE1alpha and the lectin protein OS9, and is attenuated by ER stress. ERAD deficiency causes IRE1alpha protein stabilization, accumulation and mild activation both in vitro and in vivo. Although enterocyte-specific Sel1L-knockout mice (Sel1L(DeltaIEC)) are viable and seem normal, they are highly susceptible to experimental colitis and inflammation-associated dysbiosis, in an IRE1alpha dependent but CHOP-independent manner. Hence, Sel1L-Hrd1 ERAD serves a distinct, essential function in restraint of IRE1alpha signalling in vivo by managing its protein turnover. PMID- 26551278 TI - Seasonal characteristics and current sources of OCPs and PCBs and enantiomeric signatures of chiral OCPs in the atmosphere of Vietnam. AB - Passive air samplers (PAS) were deployed concurrently at 15 locations (nine urban sites and six rural sites) in Vietnam and exposed for approximately 6 weeks from June 26, 2012 to August 26, 2012 and from December 8, 2012 to February 8, 2013. The concentration, composition and enantiomeric signatures of the target compound and Air Mass Backward Trajectories of the 15 sampling sites are presented and discussed in this study. Relatively clean air mass from ocean and similar concentrations and composition of POPs between the south and north of Vietnam indicate that local emissions is most likely the major source of POPs in Vietnam. Technical DDT and technical HCH were widely used in Vietnam and corresponding quantitative data suggests the sporadic use. The preferential degradation of (+) alpha-HCH was found in all sampling sites, which could be a regional characteristic of Vietnam. High trans-/cis-chlordane (TC/CC) ratios indicate the current use of technical chlordane for termite control. PCA estimated that main source of PCBs present in the atmosphere of Vietnam was uncontrolled discarded e waste. PMID- 26551279 TI - Modular organization of Interleukin-6 and Interleukin-11 alpha-receptors. AB - Interleukin (IL)-6 and IL-11 are the only canonical members of the IL-6 family of cytokines that induce signaling through a homodimer of the common beta-receptor glycoprotein (gp)130. A pre-requisite for signal transduction is the initial binding of the cytokines to their unique alpha-receptors, IL-6R and IL-11R. The cell-type specific expression of the two receptors determines the target cells of IL-6 and IL-11, because gp130 is ubiquitously expressed. However, ciliary neurotrophic factor (CNTF) and IL-27p28/IL-30 have been described as additional ligands for the IL-6R, underlining a remarkable plasticity among the cytokines of the IL-6 family and their receptors. In this study, we show that neither IL-6 nor IL-11 can bind to and signal through the alpha-receptor of the respective other cytokine. We further create eight chimeric IL-6/IL-11 receptors, which are all biologically active. We find that the domains D1 to D3, which contain the cytokine binding module (CBM), determine which cytokine can activate the chimeric receptor, whereas the stalk region, the transmembrane region, or the intracellular region do not participate in the ligand selectivity of the receptor and are therefore interchangeable between IL-6R and IL-11R. These results suggest a modular organization of the IL-6R and IL-11R, and a similar signal transduction complex of the two cytokines. PMID- 26551280 TI - Joint surgery in von Willebrand disease: a multicentre cross-sectional study. AB - BACKGROUND: Joint bleeds are reported by 23% of von Willebrand disease (VWD) patients and associated with orthopaedic surgery. Limited data are available on joint surgery in VWD. AIM: To assess the prevalence, indications, management and complications of joint surgery in VWD patients. METHODS: 804 VWD patients with historically lowest von Willebrand factor (VWF) activity <=30 U dL-1 completed a questionnaire on joint bleeds, joint damage and orthopaedic surgery. We retrieved additional medical file data of patients who underwent surgery on large joints (shoulder, elbow, hip, knee or ankle). RESULTS: 116 out of 804 patients (14%) reported large joint surgery. Compared to VWD patients without previous orthopaedic surgery, these 116 patients reported more frequently a history of joint bleeds and joint damage (41% vs. 20%, P < 0.001 and 61% vs. 20%, P < 0.001). Medical file data on 126 large joint surgeries in 79 VWD patients revealed that this surgery was associated with joint damage due to prior joint bleeds in 24% of the procedures. Preoperative clotting factor correction (CFC) to prevent bleeding was administered in most cases (81%). Documentation on postoperative bleeding was found in 23 surgeries (18%). CONCLUSIONS: Large joint surgery is reported by 14% of VWD patients, related to joint bleeds in 24% and seems associated with bleeding complications frequently despite perioperative CFC. PMID- 26551281 TI - A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma. AB - NUT midline carcinoma (NMC) is a fatal cancer that arises in various tissues along the upper midline of the body. The defining molecular feature of NMC is a chromosomal translocation that joins (in the majority of cases) the nuclear testis gene NUT (NUTM1) to the bromodomain protein family member 4 (BRD4) and thereby creating a fusion oncogene that disrupts cellular differentiation and drives the disease. In this study, we report the case of an adolescent NMC patient presenting with severe facial pain, proptosis and visual impairment due to a mass arising from the ethmoid sinus that invaded the right orbit and frontal lobe. Treatment involved radical resection, including exenteration of the affected eye with the view to consolidate treatment with radiation therapy; however, the patient experienced rapid tumor progression and passed away 79 days post resection. Molecular analysis of the tumor tissue identified a novel in frame BRD4-NUT transcript, with BRD4 exon 15 fused to the last 124 nucleotides of NUT exon 2 (BRD4-NUT ex15:ex2Deltant1-585). The partial deletion of NUT exon 2 was attributed to a mid-exonic genomic breakpoint and the subsequent activation of a cryptic splice site further downstream within the exon. Inhibition of the canonical 3' acceptor splice site of NUT intron 1 in cell lines expressing the most common NMC fusion transcripts (PER-403, BRD4-NUT ex11:ex2; PER-624, BRD4-NUT ex15:ex2) induced alternative splicing from the same cryptic splice site as identified in the patient. Detection of low levels of an in-frame BRD4-NUT ex11:ex2Deltant1-585 transcript in PER-403 confirmed endogenous splicing from this alternative exon 2 splice site. Although further studies are necessary to assess the clinical relevance of the increasing number of variant fusions described in NMC, the findings presented in this case identify alternative splicing as a mechanism that contributes to this pathogenic complexity. PMID- 26551282 TI - Insulin-related signaling pathways elicited by light in photoreceptor nuclei from bovine retina. AB - Retina light stimulation triggers phototransduction events as well as different signaling mechanisms in outer segments (sensorial portion) of photoreceptor cells. We have recently reported a novel light-dependent activation of diacylglycerol kinase (DAGK) and protein kinase C (PKC) at the nuclear level of photoreceptor cells. The aim of the present study was to analyze whether ex-vivo light exposure of bovine retinas also modulates insulin-related signaling pathways in nuclei from photoreceptor cells. To this end, a nuclear fraction enriched in small nuclei from photoreceptor cells (PNF) was obtained using a modified nuclear isolation protocol. In PNF obtained from bovine retinas exposed to light or darkness, the presence of insulin receptor (IR) and phosphorylated insulin receptor (pIR), the activation of Akt, p38 and extracellular signal regulated kinase (ERK1/2) and the local action of insulin on lipid kinases were studied. Immunofluorescence (IF) and Western blot (WB) studies revealed the presence of IR in photoreceptor nuclei. In PNF a light-dependent increase in IR total content was observed. The presence of activated IR (pIR) was also observed in PNF by WB, being its content higher in PNF from light than in to darkness. Light exposure also produced a significant increase in the content of p-Akt (3 fold) and p-p38 (60%) without changes in total Akt and p38. In addition, an increase in the content of total ERK1/2 (2 fold) was found without changes in p ERK/total ERK ratio, indicating that light induces translocation of p-ERK to the nucleus. Polyphosphoinositide kinase and diacylglycerol kinase (DAGK) activities were measured in isolated nuclei from light-activated or darkness-adapted retinas through the formation of polyphosphoinositides (PPIs) and phosphatidic acid (PA) using nuclear lipid substrates and [gamma-(32)P]ATP as radioactive substrate. A light-dependent increase in PPIs and PA formation was detected when isolated nuclei were exposed to 0.8 MUM insulin plus 0.2 mM vanadate. WB studies revealed that retina's exposure to insulin under light condition increased nuclear IR content. In addition, PNF exposure to insulin increased ERK1/2 phosphorylation with no changes in total ERK1/2. Our results demonstrate the presence and the functional state of IR in the nucleus from photoreceptor cells. They also show that molecular signaling components linked to tyrosine kinase receptors and MAPK pathways, such as Akt and ERK1/2, respectively, are present in photoreceptor nuclei and are regulated by insulin and light. PMID- 26551283 TI - Quantification of Food Waste Disposal in the United States: A Meta-Analysis. AB - Food waste has major consequences for social, nutritional, economic, and environmental issues, and yet the amount of food waste disposed in the U.S. has not been accurately quantified. We introduce the transparent and repeatable methods of meta-analysis and systematic reviewing to determine how much food is discarded in the U.S., and to determine if specific factors drive increased disposal. The aggregate proportion of food waste in U.S. municipal solid waste from 1995 to 2013 was found to be 0.147 (95% CI 0.137-0.157) of total disposed waste, which is lower than that estimated by U.S. Environmental Protection Agency for the same period (0.176). The proportion of food waste increased significantly with time, with the western U.S. region having consistently and significantly higher proportions of food waste than other regions. There were no significant differences in food waste between rural and urban samples, or between commercial/institutional and residential samples. The aggregate disposal rate for food waste was 0.615 pounds (0.279 kg) (95% CI 0.565-0.664) of food waste disposed per person per day, which equates to over 35.5 million tons (32.2 million tonnes) of food waste disposed annually in the U.S. PMID- 26551284 TI - The Global Nutrition Report 2015: what we need to do to advance progress in addressing malnutrition in all its forms. PMID- 26551285 TI - Epithelial-mesenchymal transition in prostatic disease. AB - A fully differentiated epithelium of the normal prostate gland allows epithelial cells to de-differentiate into mesenchymal-like derivatives via the process of epithelial-mesenchymal transition (EMT) and redifferentiate via the reverse process, mesenchymal-epithelial transition. This review discusses the phenotypic changes associated with EMT and its programming in the development of the two growth disorders of the aging prostate gland, benign prostatic hyperplasia and prostate adenocarcinoma. Considering the cellular heterogeneity that characterizes both conditions, identifying the transcriptional programming of the phenotypic framework defining EMT and its reverse process mesenchymal-epithelial transition in their pathological landscape will enable novel platforms for biomarker-driven therapeutics and their implementation in benign prostatic hyperplasia and prostate cancer. PMID- 26551286 TI - The 2014 Lush Prize awards. PMID- 26551287 TI - Barriers to the Uptake of Human-based Test Methods, and How to Overcome Them. AB - Although there is growing concern as to the questionable value of animal-based methods for determining the safety and efficacy of new medicines, which has in turn led to many groups developing innovative human-based methods, there are many barriers to their adoption for regulatory submissions. The reasons for this are various, and include a lack of confidence that the available human-based methods, be they in vivo, in silico or in vitro, can be sufficiently predictive of clinical outcomes. However, this is not the only problem: the issue of validation presents a serious impediment to progress, a particularly frustrating situation, in view of the fact that the existing animal-based methods have never themselves been formally validated. Superimposed upon this is the issue of regulatory requirements, where, although regulators may be willing to accept non-animal approaches in place of particular animal tests, nowhere is this explicitly stated in their guidelines. Such problems are far from trivial, and represent major hurdles to be overcome. In addition, there are a range of other barriers, real or self-imposed, that are hindering a more-predictive approach to establishing a new drug's clinical safety and efficacy profiles. Some of these barriers are identified, and ways forward are suggested. PMID- 26551288 TI - 2014 Lush Science Prize. AB - The Lush Prize supports animal-free testing by rewarding the most effective projects and individuals who have been working toward the goal of replacing animals in product or ingredient safety testing. A Background Paper is prepared each year, prior to the judging process, to provide the panel with a brief overview of current developments in the field of Replacement alternatives, particularly those relevant to the concept of toxicity pathways. This Background Paper includes information on recent work by the relevant scientific institutions and projects in this area, including AXLR8, OECD, CAAT, The Hamner Institutes, the Human Toxome Project, EURL ECVAM, ICCVAM, the US Tox21 Programme, the ToxCast programme, and the Human Toxicology Project Consortium. Recent developments in toxicity pathway research are also assessed by reviewing the relevant literature, with a view to presenting the two papers receiving the highest score to the judges for consideration. PMID- 26551289 TI - Toward the Replacement of Animal Experiments through the Bioinformatics-driven Analysis of 'Omics' Data from Human Cell Cultures. AB - This paper outlines the work for which Roland Grafstrom and Pekka Kohonen were awarded the 2014 Lush Science Prize. The research activities of the Grafstrom laboratory have, for many years, covered cancer biology studies, as well as the development and application of toxicity-predictive in vitro models to determine chemical safety. Through the integration of in silico analyses of diverse types of genomics data (transcriptomic and proteomic), their efforts have proved to fit well into the recently-developed Adverse Outcome Pathway paradigm. Genomics analysis within state-of-the-art cancer biology research and Toxicology in the 21st Century concepts share many technological tools. A key category within the Three Rs paradigm is the Replacement of animals in toxicity testing with alternative methods, such as bioinformatics-driven analyses of data obtained from human cell cultures exposed to diverse toxicants. This work was recently expanded within the pan-European SEURAT-1 project (Safety Evaluation Ultimately Replacing Animal Testing), to replace repeat-dose toxicity testing with data-rich analyses of sophisticated cell culture models. The aims and objectives of the SEURAT project have been to guide the application, analysis, interpretation and storage of 'omics' technology-derived data within the service-oriented sub-project, ToxBank. Particularly addressing the Lush Science Prize focus on the relevance of toxicity pathways, a 'data warehouse' that is under continuous expansion, coupled with the development of novel data storage and management methods for toxicology, serve to address data integration across multiple 'omics' technologies. The prize winners' guiding principles and concepts for modern knowledge management of toxicological data are summarised. The translation of basic discovery results ranged from chemical-testing and material-testing data, to information relevant to human health and environmental safety. PMID- 26551291 TI - The 'Genomic Revolution' and its Impact on Medical Research. PMID- 26551290 TI - Humane Education in Brazil: Organisation, Challenges and Opportunities. AB - Humane education and the debate on alternatives to harmful animal use for training is a relatively recent issue in Brazil. While animal use in secondary education has been illegal since the late 1970s, animal use in higher science education is widespread. However, alternatives to animal experiments in research and testing have recently received attention from the Government, especially after the first legislation on animal experiments was passed, in 2008. This article proposes that higher science education should be based on a critical and humane approach. It outlines the recent establishment of the Brazilian Network for Humane Education (RedEH), as a result of the project, Mapping Animal Use for Undergraduate Education in Brazil, which was recognised by the 2014 Lush Prize. The network aims to create a platform to promote change in science education in Brazil, starting by quantitatively and qualitatively understanding animal use, developing new approaches adapted to the current needs in Brazil and Latin America, and communicating these initiatives nationally. This paper explores the trajectory of alternatives and replacement methods to harmful animal use in training and education, as well as the status of humane education in Brazil, from the point of view of educators and researchers engaged with the network. PMID- 26551293 TI - 19. Russell and Burch after 1959. PMID- 26551292 TI - A New Approach to Optimising the Use of Animal Models in Drug Discovery through Big Data Sharing. PMID- 26551294 TI - Immune system disturbances in Clouston syndrome. AB - BACKGROUND: Clouston syndrome belongs to the family of ectodermal dysplasias. So far, a defective immune response has not been reported in Clouston syndrome. We report, for the first time, immunological particularities of a large multigenerational Polish family with Clouston syndrome. METHODS: Five members of the same family with Clouston syndrome, aged 6-76 years, and 20 healthy volunteers, aged 19-73 years, were enrolled in the study. In all participants, the ability of neutrophils to phagocytize opsonized Escherichia coli was assessed. Granulocyte oxidative burst was determined quantitatively, and an isolation of peripheral blood mononuclear cells and the detection of lymphocyte subsets were performed. All patients with Clouston syndrome underwent microscopic assessment of hair shafts, x-rays of the skull and hand bones, extra- and intraoral examination, and panoramic x-rays. RESULTS: Compared to the controls, all patients with Clouston syndrome presented with significantly reduced phagocytic activities of granulocytes and monocytes (P < 0.05). The percentages of granulocytes and monocytes being positive for oxidative burst were also significantly reduced in all patients with Clouston syndrome (P < 0.05). No disturbances in the percentages and absolute counts of T CD3+, T CD3+/CD4+, T CD3+/CD8+, natural killer, and B CD19+ cells were found. CONCLUSION: Although this study expands knowledge about Clouston syndrome, it also raises many questions. The results provide evidence of significantly reduced phagocytic activity and oxidative bursts of cells playing crucial roles in a nonspecific immune response. Further studies are required to understand the underlying mechanism of the hereby described abnormalities. PMID- 26551295 TI - ChromClust: A semi-supervised chromatin clustering toolkit for mining histone modifications interplay. AB - Mining patterns of histone modifications interplay from epigenomic profiles are one of the leading research areas these days. Various methods based on clustering approaches and hidden Markov models have been presented so far with some limitations. Here we present ChromClust, a semi-supervised clustering tool for mining commonly occurring histone modifications at various locations of the genome. Applying our method to 11 chromatin marks in nine human cell types recovered 11 clusters based on distinct chromatin signatures mapping to various elements of the genome. Our approach is efficient in respect to time and space usage along with the added facility of maintaining database at the backend. It outperforms the existing methods with respect to mining patterns in a semi supervised fashion mapping to various functional elements of the genome. It will aid in future by saving the resources of time and space along with efficiently retrieving the hidden interplay of histone combinations. PMID- 26551296 TI - Reoperations following Robot-Assisted Radical Cystectomy: A Decade of Experience. AB - PURPOSE: There is a paucity of data regarding the operative management of complications after robot-assisted radical cystectomy. We reviewed operative management of robot-assisted radical cystectomy specific complications during our 10-year experience with this procedure and assessed the feasibility, safety and outcomes of robot-assisted reoperations. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent surgical interventions for robot-assisted radical cystectomy specific complications between 2005 and 2015. Univariable and multivariable logistic regression models were fit to evaluate predictors of surgical intervention after robot-assisted radical cystectomy. Kaplan-Meier curves were used to describe time to surgical interventions. RESULTS: A total of 92 patients (23%) underwent surgical intervention after robot-assisted radical cystectomy. Mean followup was 27 months. Average time to any surgical intervention after cystectomy was 14 months. The reoperation rate was 5%, 2% and 16% at 30, 31 to 90 and greater than 90 days, respectively. Using the Kaplan-Meier method surgical interventions occurred at a rate of 30% at 2 years and 46% at 5 years. Interventions for ureteroileal complications were the most common (48 cases) followed by interventions for bowel obstruction, fistulas and abdominal wall related complications (11 cases). Clavien 3 or greater complications and neoadjuvant chemotherapy were associated with surgical intervention. CONCLUSIONS: Even in experienced hands the long-term complications of robot-assisted radical cystectomy are notable. Of our patients 23% required surgical interventions after the procedure. Our initial experience with robot-assisted management of robot-assisted radical cystectomy complications appears safe and feasible, although the decision to proceed is determined primarily by surgeon experience. PMID- 26551297 TI - Development of Castration Resistant Prostate Cancer can be Predicted by a DNA Hypermethylation Profile. AB - PURPOSE: Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. MATERIALS AND METHODS: Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. RESULTS: We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. CONCLUSIONS: Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It could serve as a marker of the treatment response. PMID- 26551298 TI - Quantitative Ultrasound for Measuring Obstructive Severity in Children with Hydronephrosis. AB - PURPOSE: We define sonographic biomarkers for hydronephrotic renal units that can predict the necessity of diuretic nuclear renography. MATERIALS AND METHODS: We selected a cohort of 50 consecutive patients with hydronephrosis of varying severity in whom 2-dimensional sonography and diuretic mercaptoacetyltriglycine renography had been performed. A total of 131 morphological parameters were computed using quantitative image analysis algorithms. Machine learning techniques were then applied to identify ultrasound based safety thresholds that agreed with the t1/2 for washout. A best fit model was then derived for each threshold level of t1/2 that would be clinically relevant at 20, 30 and 40 minutes. Receiver operating characteristic curve analysis was performed. Sensitivity, specificity and area under the receiver operating characteristic curve were determined. Improvement obtained by the quantitative imaging method compared to the Society for Fetal Urology grading system and the hydronephrosis index was statistically verified. RESULTS: For the 3 thresholds considered and at 100% sensitivity the specificities of the quantitative imaging method were 94%, 70% and 74%, respectively. Corresponding area under the receiver operating characteristic curve values were 0.98, 0.94 and 0.94, respectively. Improvement obtained by the quantitative imaging method over the Society for Fetal Urology grade and hydronephrosis index was statistically significant (p <0.05 in all cases). CONCLUSIONS: Quantitative imaging analysis of renal sonograms in children with hydronephrosis can identify thresholds of clinically significant washout times with 100% sensitivity to decrease the number of diuretic renograms in up to 62% of children. PMID- 26551299 TI - Identification and analysis of house-keeping and tissue-specific genes based on RNA-seq data sets across 15 mouse tissues. AB - Recently, RNA-seq has become widely used technology for transcriptome profiling due to its single-base accuracy and high-throughput speciality. In this study, we applied a computational approach on an integrated RNA-seq dataset across 15 normal mouse tissues, and consequently assigned 8408 house-keeping (HK) genes and 2581 tissue-specific (TS) genes among UCSC RefGene annotation. Apart from some basic genomic features, we also performed expression, function and pathway analysis with clustering, DAVID and Ingenuity Pathway Analysis, indicating the physiological connections (tissues) and diverse biological roles of HK genes (fundamental processes) and TS genes (tissue-corresponding processes). Moreover, we used RT-PCR method to test 18 candidate HK genes and finally identified a novel list of highly stable internal control genes: Ywhae, Ddb 1, Eif4h, etc. In summary, this study provides a new HK gene and TS gene resource for further genetic and evolution research and helps us better understand morphogenesis and biological diversity in mouse. PMID- 26551300 TI - Identification and characterization of the cDNA sequence encoding amelogenin in rabbit (Oryctolagus cuniculus). AB - Amelogenins, the most abundant proteins in tooth enamel extracellular matrix (ECM), are essential for tooth amelogenesis. The nucleotide sequence of amelogenin gene (AMEL) for rabbit, as an important member of mammals and good continuously growing incisor model, is important for comparative and evolutional study. Previous studies about rabbit amelogenin proteins got no consensus yet even as to their existence or size. In this study, with combined usage of in silico and molecular cloning technologies, we identified sequences of two transcripts of rabbit amelogenin, resulting from the alternative splicing of the 45-bp exon 4. The coding regions of the two transcripts are of 567- and 522-bp, encoding 188 and 173 amino acids including a 17-residue signal peptide, respectively. Sequence analysis revealed that rabbit amelogenin features in extremely high GC-content in nucleotide sequence and Alanine content in protein sequence. Detailed comparison of amino acid sequence with other mammals showed that the rabbit amelogenin protein is conserved in the sites and regions important for protein functions. Overall, our results uncovered the mysteries about rabbit amelogenin and revealed its sequence peculiarities. PMID- 26551301 TI - Revealing the function of a novel splice-site mutation of CHD7 in CHARGE syndrome. AB - Most cases of CHARGE syndrome are sporadic and autosomal dominant. CHD7 is a major causative gene of CHARGE syndrome. In this study, we screened CHD7 in two Turkish patients demonstrating symptoms of CHARGE syndrome such as coloboma, heart defect, choanal atresia, retarded growth, genital abnomalities and ear anomalies. Two mutations of CHD7 were identified including a novel splice-site mutation (c.2443-2A>G) and a previously known frameshift mutation (c.2504_2508delATCTT). We performed exon trapping analysis to determine the effect of the c.2443-2A>G mutation at the transcriptional level, and found that it caused a complete skip of exon 7 and splicing at a cryptic splice acceptor site. Our current study is the second study demonstrating an exon 7 deficit in CHD7. Results of previous studies suggest that the c.2443-2A>G mutation affects the formation of nasal tissues and the neural retina during early development, resulting in choanal atresia and coloboma, respectively. The findings of the present study will improve our understanding of the genetic causes of CHARGE syndrome. PMID- 26551302 TI - Manganese Oxide-Based Chemically Powered Micromotors. AB - Chemically powered micromotors represent an exciting research area in nanotechnology. Such artificial devices are typically driven by catalytic bubble formation, taking place at the solid-liquid interface. Platinum has been most frequently used for the fabrication of different micromotors due to its superior catalytic efficiency. Other materials typically suffer from slow speeds and require very high concentrations of chemical fuel. Here, we report preparation and characterization of fast moving micromotors based on manganese oxide (MnO2) with different geometrical shapes (tubes, rods, and spheres). On the basis of the results, the prepared micromotors reached the highest speeds (up to ~900 MUm s( 1) in 10% H2O2) reported to date for any MnO2-based micromotors. Moreover, they moved by bubble propulsion even at very low concentrations of peroxide fuel. Thus, MnO2 represents a promising material for the preparation of micromotors for various biomedical or environmental applications, where high speeds are desired. PMID- 26551303 TI - Impact of Water-Depletion Layer on Transport in Hydrophobic Nanochannels. AB - Recent experiments showed that by fabricating nanofluidic channels with hydrophobic materials, the measured amplitudes of both electroosmotic flow (EOF) and ionic current deviated significantly from the conventional electrokinetic modeling indication. Among these unexpected observations, the complicated dependence of EOF on the surface charge concentration of the channel wall remains most confusing. In this work we give a complete and unified picture for the phenomena by outlining the competing two mechanisms in the water-depletion layer around the channel wall: the decreasing trend of fluidic flow due to the redistribution of net charges, and the increasing trend because of the reduced solution viscosity there. Our quantitative evaluation illustrates that the alternate dominating by the two mechanisms leads to the observed transport behaviors. Furthermore, by considering the decreasing of ionic mobility in the depletion layer, our calculations show quantitative agreement with the latest experiments using BN nanotube channels. PMID- 26551272 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. AB - BACKGROUND: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS: We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive treatment group than in the standard-treatment group. CONCLUSIONS: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.). PMID- 26551304 TI - Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: The CANOA Randomized Clinical Trial. AB - IMPORTANCE: The occurrence of new-onset migraine attacks is a complication of transcatheter atrial septal defect (ASD) closure. It has been suggested that clopidogrel may reduce migraine attacks after ASD closure. OBJECTIVE: To assess the efficacy of clopidogrel, used in addition to taking aspirin, for the prevention of migraine attacks following ASD closure. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind clinical trial performed in 6 university hospitals in Canada. Participants were 171 patients with an indication for ASD closure and no history of migraine. INTERVENTIONS: Patients were randomized (1:1) to receive dual antiplatelet therapy (aspirin + clopidogrel [the clopidogrel group], n = 84) vs single antiplatelet therapy (aspirin + placebo [the placebo group], n = 87) for 3 months following transcatheter ASD closure. The first patient was enrolled in December 2008, and the last follow-up was completed in February 2015. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the monthly number of migraine days within the 3 months following ASD closure in the entire study population. The incidence and severity of new-onset migraine attacks, as evaluated by the Migraine Disability Assessment questionnaire, were prespecified secondary end points. A zero-inflated Poisson regression model was used for data analysis. RESULTS: The mean (SD) age of the participants was 49 (15) years and 62% (106) were women. Patients in the clopidogrel group had a reduced mean (SD) number of monthly migraine days within the 3 months following the procedure (0.4 [95% CI, 0.07 to 0.69] days) vs the placebo group (1.4 [95% CI, 0.54 to 2.26] days; difference, -1.02 days [95% CI, -1.94 to -0.10 days]; incident risk ratio [IRR], 0.61 [95% CI, 0.41 to 0.91]; P = .04) and a lower incidence of migraine attacks following ASD closure (9.5% for the clopidogrel group vs 21.8% for the placebo group; difference, -12.3% [95% CI, -23% to -1.6%]; odds ratio [OR], 0.38 [95% CI, 0.15 to 0.89]; P = .03). Among patients with migraines, those in the clopidogrel group had less-severe migraine attacks (zero patients with moderately or severely disabling migraine attacks vs 37% [7 patients] in the placebo group; difference, -36.8% [95% CI, -58.5% to -15.2%]; P = .046). There were no between-group differences in the rate of patients with at least 1 adverse event (16.7% [14 patients] in the clopidogrel group vs 21.8% [19 patients] in the placebo group; difference, -5.2% [95% CI, -17% to 6.6%]; P = .44). CONCLUSIONS AND RELEVANCE: Among patients who underwent transcatheter ASD closure, the use of clopidogrel and aspirin, compared with aspirin alone, resulted in a lower monthly frequency of migraine attacks over 3 months. Further studies are needed to assess generalizability and durability of this effect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799045. PMID- 26551306 TI - Laterally Mounted Azobenzenes on Platforms. AB - Triazatriangulenium ions have previously been used as platforms to prepare self assembled monolayers of functional molecules such as azobenzenes with vertical orientation and that are free-standing on gold surfaces. We have now prepared azobenzenes that are spanned between two posts which are attached on two platforms. Absorbed on a gold surface, the azobenzene should be laterally oriented at a distance of more than 4 A above and thus electronically decoupled from the surface, and the system should perform a muscle-type movement upon isomerization. PMID- 26551305 TI - Overview: New Modality for Cancer Treatment. AB - Cancer immunotherapy is now becoming a promising modality of cancer treatment upon the clinical successes of adoptive T-cell transfer and immune checkpoint blockade. At the 30th Nagoya International Cancer Treatment Symposium, Marcel R.M. van den Brink (Memorial Sloan Kettering Cancer Center, MSKCC, New York, N.Y., USA) showed novel strategies to control malignant relapse and graft-versus host disease, both major obstacles for clinical benefits in allogeneic hematopoietic stem cell transplantation. Alexander M. Lesokhin (MSKCC, New York, N.Y., USA) presented an overview of immune checkpoint blockade, particularly focusing on hematologic malignancies stressing the importance of immunomonitoring to identify biomarkers. PMID- 26551307 TI - Rotational Diffusion of Nonpolar and Ionic Solutes in 1-Alkyl-3-methylimidazolium Tetrafluoroborate-LiBF4 Mixtures: Does the Electrolyte Induce the Structure Making or Structure-Breaking Effect? AB - Rotational diffusion of three structurally similar solutes, 9-phenylanthracene (9 PA), fluorescein (FL), and rhodamine 110 (R110), has been investigated in 1-butyl 3-methylimidazolium tetrafluoroborate-lithium tetrafluoroborate ([BMIM][BF4] LiBF4) mixtures to understand the influence of the added electrolyte on the mobility of nonpolar, anionic, and cationic solute molecules. It has been observed that the reorientation times of the nonpolar solute 9-PA become progressively shorter with an increase in the concentration of LiBF4 at a given viscosity (eta) and temperature (T). In the case of ionic solutes also, a decrease in the reorientation times has been observed upon the addition of the electrolyte compared to those obtained in the neat ionic liquid at a given eta/T. However, this decrease is found to be independent of [LiBF4]. 9-PA being a nonpolar solute is located in the nonpolar domains of the ionic liquid. An enhancement in [LiBF4] leads to an increase in the sizes of the nonpolar domains resulting in the faster rotation of the solute. Anionic solute FL and cationic solute R110, which are located in the ionic region experience specific interactions with the cation and anion of the ionic liquid, respectively. In the presence of electrolyte, however, the strengths of these specific interactions diminish as the ions of the ionic liquid are not readily accessible to the solute molecules due to the organized structure, which results in faster rotation. These observations suggest that addition of LiBF4 induces a structure-making effect in the ionic liquid. PMID- 26551308 TI - [At the border of pluri- and multipotency: the neural crest stem cells]. AB - The neural crest is a transient, multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the neuronal and glial components of the peripheral nervous system to the ectomesenchymal derivatives of the craniofacial area and pigment cells in the skin. Intriguingly, the neural crest derived stem cells are not only present in the embryonic neural crest, but also in their target tissues in the fetus and adult. These postmigratory stem cells, at least partially, resemble their multipotency. Moreover, fully differentiated neural crest-derived cells such as Schwann cells and melanocytes are able to dedifferentiate into stem-like progenitors. Here the authors review current understanding of this unique plasticity and its potential application in stem cell biology as well as in regenerative medicine. PMID- 26551309 TI - [Inborn error of cholesterol biosynthesis: Smith-Lemli-Opitz syndrome]. AB - Smith-Lemli-Opitz syndrome is an autosomal recessive mental retardation and multiple malformation syndrome caused by deficiency of the 7-dehydrocholesterol reductase, the enzyme catalyzing the last step in cholesterol biosynthesis. The authors summarize the pathophysiology, epidemiology, clinical picture, diagnostics and therapy of the disease based on a review of the international literature. Since 2004, fourteen patients have been diagnosed with Smith-Lemli Opitz syndrome in Hungary, which suggests an underdiagnosis of the disease based upon estimated incidence data. Due to deficiency of the 7-dehydrocholesterol reductase, serum cholesterol concentration is low and 7-dehydrocholesterol concentration is elevated in blood and tissues; the latter being highly specific for the syndrome. Detection of disease-causing mutations makes the prenatal diagnosis possible. The clinical spectrum is wide, the most common symptom is syndactyly of the second and third toes. Standard therapy is cholesterol supplementation. Recent publications suggest that oxidative compounds of 7 dehydrocholesterol may play a role in the pathophysiology of the disease as well. PMID- 26551310 TI - [Palliative care in non-cancer, chronic, progressive diseases]. AB - Malignant and other chronic diseases cause the death of 2.5 million people in Europe annually. It is anticipated that this number will grow due to the aging of the European population. The death of a significant proportion of patients having progressive chronic disease is preceded by an extended end of life stadium. In this stage the patients have severe symptoms and pain that necessitate their symptomatic treatment and palliative care. The assessment of the life expectancy of patients, estimation of the prognosis of their illness and, therefore, selection of patients with a need of intensified palliative care often pose difficulties. This paper provides a summary on the basic elements of "good palliative care". It introduces the most frequent models for the procession of chronic diseases and those indicators that help practicing doctors to recognise easier patients with a need of intensified palliative care, and as a result provides more adequate medical attendance that is better suited to the specific needs of the patients. PMID- 26551311 TI - [Effect of healthy diet and physical activity on the level of non-HDL cholesterol in obese subjects without cardiovascular disease and diabetes mellitus]. AB - INTRODUCTION: Prevention program including lifestyle changes was initiated with the participation of obese and overweight subjects recruited from the practices of 29 family doctors. AIM: The aim of the author was to analyse changes of non HDL-cholesterol levels, especially when triglyceride levels were above 2.26 mmol/l, and when non-HDL cholesterol levels were high in association with low HDL cholesterol levels in overweight or obese subjects who had no cardiovascular disease and diabetes mellitus. METHOD: Data obtained from 1192 subjects (424 men and 768 women) before and 12 month after inclusion into the prevention program was analysed. RESULTS: The average level of non-HDL-cholesterol in the whole group of subjects decreased from 4.74 to 4.64 mmol/l, but the change was not significant. However, the average concentration of non-HDL-cholesterol was reduced significantly from 4.87 to 4.4 mmol/l in men, whereas no significant change was detected in women. In cases when triglyceride levels were higher than 2.26 mmol/l, the non-HDL-cholesterol level was reduced by 0.65 mmol/l. In cases when the non-HDL-cholesterol level was high in association with low HDL cholesterol level, the non-HDL-cholesterol was significantly decreased from 5.22 to 4.48 mmol/l. In addition, in cases when HDL-cholesterol levels were low, the average level of the HDL-cholesterol significantly increased from 0.84 to 1.3 mmol/l. CONCLUSIONS: Lifestyle changes decrease the level of atherogenic lipid fractions, particularly in men with high triglyceride levels. Improvement of the atherogenic lipid profile in response to lifestyle changes is related not only to the reduction of atherogenic lipid fractions, but also to the increase of HDL cholesterol level. PMID- 26551312 TI - [A new questionnaire for the assessment of parental health literacy]. AB - INTRODUCTION: Parental health literacy is an important factor of pediatric health. Although it is thorougly studied in other countries, neither proper definition, nor adequate tool for its measurement exists in Hungarian. AIM: The aim of this work was to define the dimensions of parental health literacy and to introduce a questionnaire for its measurement. METHOD: Opinions of parents, pediatric nurses and pediatricians on parental health literacy were used to establish the definition and basic components. Based on these and previously standardized tests a new questionnaire was developed. RESULTS: Four dimensions of parental health literacy were formulated such as knowledge, functional literacy, self-confidence and motivation. The new questionnaire assesses all four dimension through eight topics. CONCLUSIONS: This is the first culturally adapted definition and test of parental health literacy in Hungarian. With its application the efficacy of both primary care services and health education may be improved and the correlation between parental health literacy and pediatric health may be properly studied. PMID- 26551314 TI - CYP2D6 copy number distribution in the US population. AB - The cytochrome P450 2D6 (CYP2D6) gene is perhaps the most well characterized gene involved in drug metabolism and is known to have both gene duplication and deletion variants that are inheritable and stable. In a set of over 30,000 deidentified clinical samples we found that 12.6% of all patients tested had zero, one, or three or more copies of the CYP2D6 gene. On the basis of the combined frequency and impact of these variants, we believe that CYP2D6 copy number variation may account for the single most impactful genetic anomaly as it relates to pharmacogenetic directed therapies. PMID- 26551315 TI - Metalaxyl Resistance in Phytophthora infestans: Assessing Role of RPA190 Gene and Diversity Within Clonal Lineages. AB - Prior work has shown that the inheritance of resistance to metalaxyl, an oomycete specific fungicide, is complex and may involve multiple genes. Recent research indicated that a single nucleotide polymorphism (SNP) in the gene encoding RPA190, the largest subunit of RNA polymerase I, confers resistance to metalaxyl (or mefenoxam) in some isolates of the potato late blight pathogen Phytophthora infestans. Using both DNA sequencing and high resolution melt assays for distinguishing RPA190 alleles, we show here that the SNP is absent from certain resistant isolates of P. infestans from North America, Europe, and Mexico. The SNP is present in some members of the US-23 and US-24 clonal lineages, but these tend to be fairly sensitive to the fungicide based on artificial media and field test data. Diversity in the level of sensitivity, RPA190 genotype, and RPA190 copy number was observed in these lineages but were uncorrelated. Controlled laboratory crosses demonstrated that RPA190 did not cosegregate with metalaxyl resistance from a Mexican and British isolate. We conclude that while metalaxyl may be used to control many contemporary strains of P. infestans, an assay based on RPA190 will not be sufficient to diagnose the sensitivity levels of isolates. PMID- 26551316 TI - Nanomedicine for Infectious Disease Applications: Innovation towards Broad Spectrum Treatment of Viral Infections. AB - Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. PMID- 26551318 TI - Need for Rectal Biopsy for Childhood Constipation Predicts Severity of Illness and Need for Laxatives. AB - OBJECTIVES: This study aimed to examine the long-term clinical outcomes of children with severe constipation, as defined by need for rectal biopsy (RB), and to determine which baseline characteristics were predictors of successful outcome. METHODS: Children with severe constipation who underwent RB for evaluation of Hirschsprung disease at a tertiary medical center were eligible. A cohort of children with constipation without a history of RB served as controls (matched 2:1 by sex and age). Retrospective chart review of clinic visits was performed at baseline, 3, 6, 12, 18, and 24 months. Successful clinical outcomes were defined as >=3 bowel movements weekly for >=4 weeks, with <=2 fecal incontinence episodes monthly, irrespective of laxative use. RESULTS: A total of 175 RB children (90 boys, mean age: 6.7 years) were matched to 350 controls. Mean duration of constipation symptoms before intake in the RB group was significantly longer compared with controls (3.7 vs 0.4 years, P < 0.001). By 24 months, the cumulative percentage of children achieving at least 1 period of successful outcome was significantly higher in the control group compared with RB population (73% vs 24%, P < 0.001). Multivariate analysis revealed that younger age (P = 0.001, odds ratio 0.87) and shorter duration of constipation before RB (P = 0.03, odds ratio 0.45) were significant predictors of successful outcome. CONCLUSIONS: Only one-quarter of patients with severe constipation achieved successful outcome during 2-year follow-up. Younger age and shorter duration of constipation at time of biopsy were predictors of successful outcomes, emphasizing the importance of early diagnosis and initiation of treatment in this population. PMID- 26551317 TI - Practical Use of Infliximab Concentration Monitoring in Pediatric Crohn Disease. AB - OBJECTIVES: Therapeutic drug monitoring (TDM) that guides infliximab (IFX) intensification strategies has been shown to improve IFX efficacy. We conducted a review to evaluate the utility of TDM in the assessment and subsequent management of IFX loss of response in our pediatric population with Crohn disease (CD). METHODS: Single-center retrospective study of patients with CD receiving IFX that had TDM from December 2009 to September 2013. We defined subtherapeutic trough as a drug level below the detection limit of the Prometheus enzyme-linked immunoabsorbant assay and Anser reference values (1.4 and 1 MUg/mL, respectively) or a mid-interval level <12 MUg/mL. RESULTS: One hundred ninety-one IFX concentration tests were performed on 72 patients with CD with loss of response to therapy as the primary indication (72%). 34% of all TDM were subtherapeutic. After initial TDM, 25 of the 72 patients received regimen intensification with 72% in clinical remission at 6 months. Including all of the TDM that resulted in IFX dose intensification, we found a significant improvement in 6-month remission rates whether intensification followed mid-interval (88% remission) or trough (56% remission) testing (P = 0.026). Antibody to infliximab was found in 14 patients with 5 occurring in the first year of therapy. Furthermore, 71% of patients with antibody to infliximab that were switched to an alternative anti tumor necrosis factor achieved clinical remission at six months. In multivariable regression analysis, we found IFX dose (mg/kg), IFX dosing frequency (weeks), and the erythrocyte sedimentation rate at the previous infusion were significantly associated with the IFX concentration. CONCLUSIONS: TDM in our pediatric population with CD led to informed clinical decisions and improved rates of clinical remission. PMID- 26551319 TI - Decreased Expression of Enterocyte Nutrient Assimilation Genes and Proteins in the Small Intestine of Cystic Fibrosis Mouse. AB - OBJECTIVES: Cystic fibrosis (CF) has major effects on the intestinal tract with potential consequences on nutrition, but these are not fully understood. I investigated the possibility of altered enterocyte maturation in CF, as suggested by decreased enterocyte nutrient assimilation gene expression in published transcriptome analysis of the small intestine of CF mouse. METHODS: In CF and wild-type (WT) mice, enterocyte gene/protein expression was analyzed by quantitative realtime polymerase chain reaction (qRT-PCR), enzyme histochemistry, immunohistochemistry, and Western blot. One group of mice was maintained on a control liquid diet; to manipulate the gut microbiota, a second group was treated with oral antibiotics; to improve hydration of the gut lumen, a third group was given a laxative drinking solution. RESULTS: On the control diet in the CF intestine, there were decreased levels (67%-85% reduction of WT levels) of enterocyte genes/proteins. Antibiotics did not normalize the expression of enterocyte markers in the CF mouse. In contrast, the laxative treatment of CF mice significantly increased expression to near WT levels. CONCLUSIONS: These studies suggest that the environment of the CF intestinal lumen plays a role in reduced maturation of enterocytes. Because changing the gut lumen environment can affect enterocyte maturation, this is not a cell-autonomous effect of loss of CF transmembrane conductance regulator. PMID- 26551320 TI - Electrochemically Functionalized Seamless Three-Dimensional Graphene-Carbon Nanotube Hybrid for Direct Electron Transfer of Glucose Oxidase and Bioelectrocatalysis. AB - Three-dimensional seamless chemical vapor deposition (CVD) grown graphene-carbon nanotubes (G-CNT) hybrid film has been studied for its potential in achieving direct electron transfer (DET) of glucose oxidase (GOx) and its bioelectrocatalytic activity in glucose detection. A two-step CVD method was employed for the synthesis of seamless G-CNT hybrid film where CNTs are grown on already grown graphene film on copper foil using iron as a catalyst. Physical characterization using SEM and TEM show uniform dense coverage of multiwall carbon nanotubes (MWCNT) grown directly on graphene with seamless contacts. The G CNT hybrid film was electrochemically modified to introduce oxygenated functional groups for DET favorable immobilization of GOx. Pristine and electrochemically functionalized G-CNT film was characterized by electrochemical impedance spectroscopy (EIS), cyclic voltammetry, X-ray photoelectron-spectroscopy, and Raman spectroscopy. The DET between GOx and electrochemically oxidized G-CNT electrode was studied using cyclic voltammetry which showed a pair of well defined and quasi-reversible redox peaks with a formal potential of -459 mV at pH 7 corresponding to the redox site of GOx. The constructed electrode detected glucose concentration over the clinically relevant range of 2-8 mM with the highest sensitivity of 19.31 MUA/mM/cm(2) compared to reported composite hybrid electrodes of graphene oxide and CNTs. Electrochemically functionalized CVD grown seamless G-CNT structure used in this work has potential to be used for development of artificial mediatorless redox enzyme based biosensors and biofuel cells. PMID- 26551321 TI - Wearing a Wetsuit Alters Upper Extremity Motion during Simulated Surfboard Paddling. AB - Surfers often wear wetsuits while paddling in the ocean. This neoprene covering may be beneficial to upper extremity movement by helping to improve proprioceptive acuity, or it may be detrimental by providing increased resistance. The purpose of this study was to evaluate the effects of wearing a wetsuit on muscle activation, upper extremity motion, heart rate, and oxygen consumption during simulated surfboard paddling in the laboratory. Twelve male, recreational surfers performed two paddling trials at a constant workload on a swim bench ergometer both with and without a wetsuit. Kinematic data and EMG were acquired from the right arm via motion capture, and oxygen consumption and heart rate were recorded with a metabolic cart and heart rate monitor. Wearing a wetsuit had no significant effect on oxygen consumption or heart rate. A significant increase in EMG activation was observed for the middle deltoid but not for any of the other shoulder muscle evaluated. Finally, approximate entropy and estimates of the maximum Lyapunov exponent increased significantly for vertical trajectory of the right wrist (i.e. stroke height) when a wetsuit was worn. These results suggest that a 2mm wetsuit has little effect on the energy cost of paddling at lower workloads but does affect arm motion. These changes may be the result of enhanced proprioceptive acuity due to mechanical compression from the wetsuit. PMID- 26551322 TI - Soybean phosphatidylcholine liposomes as model membranes to study lipid peroxidation photoinduced by pterin. AB - Oxidized pterins, efficient photosensitizers under UVA irradiation, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Soybean phosphatidylcholine (SoyPC) liposomes were employed as model membranes to investigate if pterin (Ptr), the parent compound of oxidized pterins, is able to photoinduced lipid peroxidation. Size exclusion chromatography and dialysis experiments showed that Ptr is not encapsulated inside the liposomes and the lipid membrane is permeable to this compound. The formation of conjugated dienes and trienes, upon UVA irradiation, was followed by absorption at 234 and 270 nm, respectively. The photoproducts were characterized by mass spectrometry and oxygenation of SoyPC was demonstrated. In addition, analysis of MS/MS spectra suggested the formation hydroperoxides. Finally, the biological implications of the findings are discussed. PMID- 26551323 TI - Sub-ten-nanometer heterogeneity of solid supported lipid membranes determined by solution atomic force microscopy. AB - Visually detecting nanoscopic structures in lipid membranes is important for elucidating lipid-lipid interactions, which are suggested to play a role in mediating membrane rafts. We use solution atomic force microscopy (AFM) to study lateral and normal organization in multicomponent lipid membranes supported by mica substrate. Nanoscopic heterogeneity is observed in a three-component system composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/brain sphingomyelin (bSM)/cholesterol (Chol). We find sub-ten-nanometer correlation lengths that are used to describe membrane lateral organization. In addition, we find that the correlation length is independent on cholesterol concentration, while the height fluctuation (variation) is not. To explore the mechanism that controls the size of membrane heterogeneity, we extend our study to a four component system composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/POPC/bSM/Chol. By systematically adjusting the relative amount of DOPC and POPC, we obtain macroscopic-to-nanoscopic size transition of membrane heterogeneity. In contrast to the results from vesicle based fluorescence microscopy, we find that the structural transition is continuous both in the lateral and normal directions. We compare our nanoscopic structures to two theoretical models, and find that both the critical fluctuations and the nanodomain models are not sufficient to account for our solution AFM data. Finally, we propose a nanoheterogeneity model that could serve as the organization principle of the observed nanoscopic structures in multicomponent lipid membranes. PMID- 26551324 TI - Boosting Local Field Enhancement by on-Chip Nanofocusing and Impedance-Matched Plasmonic Antennas. AB - Strongly confined surface plasmon-polariton modes can be used for efficiently delivering the electromagnetic energy to nanosized volumes by reducing the cross sections of propagating modes far beyond the diffraction limit, that is, by nanofocusing. This process results in significant local-field enhancement that can advantageously be exploited in modern optical nanotechnologies, including signal processing, biochemical sensing, imaging, and spectroscopy. Here, we propose, analyze, and experimentally demonstrate on-chip nanofocusing followed by impedance-matched nanowire antenna excitation in the end-fire geometry at telecom wavelengths. Numerical and experimental evidence of the efficient excitation of dipole and quadrupole (dark) antenna modes are provided, revealing underlying physical mechanisms and analogies with the operation of plane-wave Fabry-Perot interferometers. The unique combination of efficient nanofocusing and nanoantenna resonant excitation realized in our experiments offers a major boost to the field intensity enhancement up to ~12000, with the enhanced field being evenly distributed over the gap volume of 30 * 30 * 10 nm(3), and promises thereby a variety of useful on-chip functionalities within sensing, nonlinear spectroscopy and signal processing. PMID- 26551325 TI - Haemaphysalis longicornis tick bites are a possible cause of red meat allergy in Japan. AB - Recent studies revealed that Amblyomma or Ixodes tick bites may cause red meat allergy, in which galactose-alpha-1,3-galactose (alpha-Gal) is a major IgE binding epitope. The incidence of red meat allergy is high in Shimane Prefecture, as is tick-transmitted Japanese spotted fever. Therefore, we speculated that tick bites may cause these meat allergies. The carbohydrate alpha-Gal was detected in the salivary gland protein of Haemaphysalis longicornis (H. longicornis), the vector for Japanese spotted fever, by immunoblotting using anti-alpha-Gal antibody. H. longicornis salivary gland protein-specific IgE was detected in the sera of 24 of 30 patients with red meat allergies. Sensitization to tick salivary gland protein containing alpha-Gal is possibly a major etiology of red meat allergy; the carbohydrate plays a crucial role in its allergenicity. These results further indicate that the alpha-Gal epitope is present not only in Amblyomma or Ixodes, but also in Haemaphysalis. PMID- 26551327 TI - Breastsleeping or not? PMID- 26551326 TI - Trinitrotoluene Induces Endoplasmic Reticulum Stress and Apoptosis in HePG2 Cells. AB - BACKGROUND: This study aims to describe trinitrotoluene (TNT)-induced endoplasmic reticulum stress (ERS) and apoptosis in HePG2 cells. MATERIAL AND METHODS: HePG2 cells were cultured in vitro with 0, 6, 12, or 24 MUg/ml TNT solution for 12, 24, and 48 h. Western blotting was performed to detect intracellular ERS-related proteins, including glucose-regulated protein (GRP) 78, GRP94, Caspase 4, p-Jun N terminal kinase (JNK), and C/EBP homologous protein (CHOP). Real-time PCR was used to measure mRNA expression from the respective genes. RESULTS: The expressions of ERS-related proteins GRP78 and GRP94 as well as mRNA and protein expression of ERS signaling apoptotic CHOP in the TNT treatment group were significantly increased. In addition, the mRNA and protein expression levels of ERS-induced apoptotic protein Caspase-4 were significantly increased. Flow cytometry revealed that after TNT treatment, the apoptosis rate also significantly increased. CONCLUSIONS: TNT could increase the expression levels of GRP78, GRP94, Caspase-4, and CHOP in HePG2 cells; this increase in protein expression might be involved in HePG2 apoptosis through the induction of the ERS pathway. PMID- 26551329 TI - A Novel, Real-Time, In Vivo Mouse Retinal Imaging System. AB - PURPOSE: To develop an efficient, low-cost instrument for robust real-time imaging of the mouse retina in vivo, and assess system capabilities by evaluating various animal models. METHODS: Following multiple disappointing attempts to visualize the mouse retina during a subretinal injection using commercially available systems, we identified the key limitation to be inadequate illumination due to off axis illumination and poor optical train optimization. Therefore, we designed a paraxial illumination system for Greenough-type stereo dissecting microscope incorporating an optimized optical launch and an efficiently coupled fiber optic delivery system. Excitation and emission filters control spectral bandwidth. A color coupled-charged device (CCD) camera is coupled to the microscope for image capture. Although, field of view (FOV) is constrained by the small pupil aperture, the high optical power of the mouse eye, and the long working distance (needed for surgical manipulations), these limitations can be compensated by eye positioning in order to observe the entire retina. RESULTS: The retinal imaging system delivers an adjustable narrow beam to the dilated pupil with minimal vignetting. The optic nerve, vasculature, and posterior pole are crisply visualized and the entire retina can be observed through eye positioning. Normal and degenerative retinal phenotypes can be followed over time. Subretinal or intraocular injection procedures are followed in real time. Real-time, intravenous fluorescein angiography for the live mouse has been achieved. CONCLUSIONS: A novel device is established for real-time viewing and image capture of the small animal retina during subretinal injections for preclinical gene therapy studies. PMID- 26551330 TI - Phenotype Characteristics of Fellow Eyes in Patients With Early Onset of Neovascular Age-Related Macular Degeneration. AB - PURPOSE: To investigate phenotype characteristics of fellow eyes in patients with early onset of neovascular age-related macular degeneration (NVAMD). METHODS: Patients with new-onset unilateral NVAMD between 50 and 65 years (n = 57, early onset choroidal neovascularization [CNV] group) or >80 years (n = 47, late-onset CNV group) or with nonneovascular AMD (n = 98, no-CNV group) were included. Fellow eyes in both CNV groups and the eyes with the more severe AMD staging in the no-CNV group were used to evaluate number and size of macular drusen, extramacular drusen (EMD), pigmentary abnormalities, and retinal pigment epithelium (RPE) atrophy on color photographs and hyperreflective dots (HRD) and reticular pseudodrusen (RPD) on spectral-domain optical coherence tomography (SDOCT) scans. Regression analysis was used to compare groups. RESULTS: Occurrence of >20 macular drusen was more frequent in the early-onset CNV group than the late-onset CNV group (odds ratio [OR] 2.93; P = 0.01) or the no-CNV group (OR 2.17; P = 0.02). Retinal pigment epithelium atrophy, RPD, and HRD appeared less frequently in the early-onset CNV group than in the late-onset CNV group (RPE atrophy: OR 0.11; P = 0.005; RPD: OR 0.04; P = 9.38 * 10-10, HRD: OR 0.30; P = 0.004) and no-CNV group (RPE atrophy: OR 0.12; P = 0.005; RPD: OR 0.40, P = 0.03, HRD: not significant). No differences were detected regarding presence of large drusen, pigmentary abnormalities, and EMD. CONCLUSIONS: A large number of macular drusen in the fellow eye appeared to be characteristic for early onset of NVAMD, whereas RPE atrophy, HRD, and RPD were more frequently present in AMD patients > 80 years. Prospective trials with patients converting to NVAMD are required to further analyze morphologic characteristics for early versus late development of advanced AMD. PMID- 26551331 TI - Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers. AB - PURPOSE: To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort. METHODS: Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (30 degrees , 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured. RESULTS: In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range. CONCLUSIONS: With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible. PMID- 26551333 TI - Effects of Flavor and Texture on the Sensory Perception of Gouda-Type Cheese Varieties during Ripening Using Multivariate Analysis. AB - The impact of flavor composition, texture, and other factors on desirability of different commercial sources of Gouda-type cheese using multivariate analyses on the basis of sensory and instrumental analyses were investigated. Volatile aroma compounds were measured using headspace solid-phase microextraction gas chromatography/mass spectrometry (GC/MS) and steam distillation extraction (SDE) GC/MS, and fatty acid composition, low-molecular-weight compounds, including amino acids, and organic acids, as well pH, texture, and color were measured to determine their relationship with sensory perception. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to discriminate between 2 different ripening periods in 7 sample sets, revealing that ethanol, ethyl acetate, hexanoic acid, and octanoic acid increased with increasing sensory attribute scores for sweetness, fruity, and sulfurous. A partial least squares (PLS) regression model was constructed to predict the desirability of cheese using these parameters. We showed that texture and buttery flavors are important factors affecting the desirability of Gouda-type cheeses for Japanese consumers using these multivariate analyses. PMID- 26551332 TI - Compromised Optic Nerve Blood Flow and Autoregulation Secondary to Neural Degeneration. AB - PURPOSE: To test the hypothesis that optic nerve head (ONH) blood flow (BF) and autoregulation compromise are consequences of optic nerve degeneration induced by surgical optic nerve transection (ONT). METHODS: In both eyes of five nonhuman primates, peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by spectral-domain optical coherence tomography. Optic nerve head BF and dynamic autoregulation responses to a rapid manometric IOP increase (from 10-40 mm Hg) were measured by Laser Speckle Flowgraphy. The measurements were conducted every 10 to 15 days before and after unilateral ONT. Post-ONT measurements were repeated until RNFLT in the ONT eye was reduced by more than 40% of baseline value. RESULTS: After ONT, RNFLT, and ONH BF progressively declined over time (P < 0.0001 and P = 0.02, respectively). Longitudinal changes between the two were highly correlated (P < 0.0001). When data was grouped by test session, the first significant decreases for RNFLT and BF were found 13 +/- 0.8 and 24 +/- 3.2 days post ONT, respectively (P < 0.05, both). At the final time point (55 +/- 0.5 days post ONT), RNFLT, and BF were reduced by 44% +/- 2.0% and 38 +/- 5.0% from baseline, respectively. Dynamic autoregulation analysis showed marginal increased response time in post-ONT eyes (P = 0.05). Control eyes showed no longitudinal changes for any parameter. CONCLUSIONS: The close association between RNFLT loss and ONH BF decrease following optic nerve degeneration demonstrated a clear cause and effect relationship. Increased BF response time appears to be a sign of dynamic autoregulation dysfunction in this ONT model. PMID- 26551334 TI - NIR-Laser-Switched In Vivo Smart Nanocapsules for Synergic Photothermal and Chemotherapy of Tumors. AB - In vivo MEO2 MA@MEO2 MA-co-OEGMA-CuS-DOX (G-CuS-DOX) nanocapsules increase the temperature of tumors from room temperature to 57 degrees C due to the photothermal effect under irradiation from a 915-nm laser. When the temperature exceeds 42 degrees C, photothermal therapy of G-CuS-DOX is switched on. Simultaneously, higher temperatures (>LCST, 42 degrees C) induce volume shrinkage of G-CuS-DOX in vivo, leading to the controllable release of the anticancer drug DOX. If the NIR laser is switched off, both therapy effects are interrupted immediately. PMID- 26551335 TI - First report of the nutritional profile and antioxidant potential of Holothuria arguinensis, a new resource for aquaculture in Europe. AB - This work reports for the first time the nutritional profile and antioxidant potential of the edible sea cucumber Holothuria arguinensis from the North eastern Atlantic. H. arguinensis has high levels of protein, with the amino acids profile dominated by alanine, glycine and proline and low lysine/arginine ratios. Its carbohydrate and energetic contents are also low as well as the total lipid levels, although its lipid profile is rich in polyunsaturated fatty acids (PUFA), especially arachidonic, eicosapentaenoic and docosahexaenoic acids. In addition, H. arguinensis has high levels of calcium. The water and ethanol extracts show ability to scavenge free radicals and to chelate copper and iron ions. Our results indicate that H. arguinensis has a balanced nutritional quality suitable for human consumption. In addition, it contains compounds with antioxidant potential; thus its intake can contribute for a healthy and well-balanced diet. PMID- 26551336 TI - Isothermal Amplification of Nucleic Acids. AB - Isothermal amplification of nucleic acids is a simple process that rapidly and efficiently accumulates nucleic acid sequences at constant temperature. Since the early 1990s, various isothermal amplification techniques have been developed as alternatives to polymerase chain reaction (PCR). These isothermal amplification methods have been used for biosensing targets such as DNA, RNA, cells, proteins, small molecules, and ions. The applications of these techniques for in situ or intracellular bioimaging and sequencing have been amply demonstrated. Amplicons produced by isothermal amplification methods have also been utilized to construct versatile nucleic acid nanomaterials for promising applications in biomedicine, bioimaging, and biosensing. The integration of isothermal amplification into microsystems or portable devices improves nucleic acid-based on-site assays and confers high sensitivity. Single-cell and single-molecule analyses have also been implemented based on integrated microfluidic systems. In this review, we provide a comprehensive overview of the isothermal amplification of nucleic acids encompassing work published in the past two decades. First, different isothermal amplification techniques are classified into three types based on reaction kinetics. Then, we summarize the applications of isothermal amplification in bioanalysis, diagnostics, nanotechnology, materials science, and device integration. Finally, several challenges and perspectives in the field are discussed. PMID- 26551337 TI - Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3 3 Protein-Protein Interactions. AB - Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan parasite Giardia duodenalis, which affects annually over 200 million people worldwide. The limited antigiardial drug arsenal and the emergence of clinical cases refractory to standard treatments dictate the need for new chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively involved in protein-protein interactions (PPIs) with pSer/pThr clients, represents a highly promising target. Despite homology with human counterparts, the single 14 3-3 of G. duodenalis (g14-3-3) is characterized by a constitutive phosphorylation in a region critical for target binding, thus affecting the function and the conformation of g14-3-3/clients interaction. However, to approach the design of specific small molecule modulators of g14-3-3 PPIs, structural elucidations are required. Here, we present a detailed computational and crystallographic study exploring the implications of g14-3-3 phosphorylation on protein structure and target binding. Self-Guided Langevin Dynamics and classical molecular dynamics simulations show that phosphorylation affects locally and globally g14-3-3 conformation, inducing a structural rearrangement more suitable for target binding. Profitable features for g14-3-3/clients interaction were highlighted using a hydrophobicity-based descriptor to characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in complex with a mode-1 prototype phosphopeptide was solved and combined with structure-based simulations to identify molecular features relevant for clients binding to g14-3-3. The data presented herein provide a further and structural understanding of g14-3-3 features and set the basis for drug design studies. PMID- 26551338 TI - Developing ALK Immunohistochemistry and In Situ Hybridization Proficiency Testing for Non-Small Cell Lung Cancer in Canada: Canadian Immunohistochemistry Quality Control Challenges and Successes. AB - Intrachromosomal rearrangements involving the ALK gene are found in 3% to 5% of non-small cell lung cancers. Crizotinib is a tyrosine kinase inhibitor that has been shown to prolong progression-free survival in patients with advanced non small cell lung cancer harboring ALK gene rearrangements. In Canada, ALK immunohistochemistry (IHC) is used as a screening test before confirmation by fluorescence in situ hybridization (FISH). Canadian Immunohistochemistry Quality Control (CIQC) provides ALK (Lung Cancer) proficiency testing (PT) for Canadian IHC laboratories. Samples included 32 previously characterized cases (IHC and FISH) either from the Canadian ALK (CALK) project or from CIQC reference laboratories. The same design was used for both runs. A total of 20 laboratories participated in Run 1 and 22 in Run 2. Some laboratories participated in the anticipation of future need and used the PT exercise as a part of test development and validation. Results of the IHC testing were first self-reported using the CIQC TMA Scorer and then evaluated by expert assessment. FISH results were self-reported only. Participants also reported details about IHC and FISH protocols. The kappa-values were calculated, for which values >0.80 were used as acceptable results, respectively. The pass rate between the 2 runs and between different primary antibodies were compared. Six of the 22 protocols (27%) in Run 1 and 15 of the 22 (68%) protocols in Run 2 passed the CIQC PT criteria for IHC testing. The increase in the pass rate for Run 2 was significant (P=0.03, Wilcoxon signed-rank test). All reported FISH results were correct. CALK laboratories had significantly higher kappa-values than non-CALK laboratories (P=0.002, t test). PT for IHC for rare diseases such as ALK-positive lung cancer is feasible, but challenging. The academic nature of the CIQC program and collaboration on a national level facilitated the development of appropriate PT samples. Participating laboratories made use of the PT exercise either to confirm that their testing was properly calibrated or to improve their protocols, which was confirmed by the achievement of significantly better results in Run 2. They also used CIQC's PT program for new test development and optimization. PMID- 26551340 TI - Patterns and Significance of PIM Kinases in Urothelial Carcinoma. AB - BACKGROUND: The Provirus integrating site Moloney murine leukemia virus (Pim) family are proteins with serine/threonine kinase activity. Studies have demonstrated overexpression of Pims in cancer. To our knowledge, only a single study has examined Pim-1 in urothelial carcinoma. The aim of this investigation was to evaluate Pim-1, Pim-2, and Pim-3 in urothelial carcinoma and assess for expression that may contribute to disease progression and serve as a site for targeted therapy. METHODS: This retrospective study included 137 cases taken from specimens from the University of Utah, Department of Pathology (2008 to 2011). Tissue was stained with antibodies against Pim-1, Pim-2, and Pim-3. Cases were classified into 3 groups, based upon current World Health Organization criteria (invasive high-grade urothelial carcinoma [IHG] [n=84], noninvasive high-grade urothelial carcinoma/carcinoma in situ [n=32], and noninvasive low-grade urothelial carcinoma [NILG] [n=21]). Cases were scored and recorded as positive or negative on the basis of the percentage of cells with cytoplasmic and/or nuclear staining. RESULTS: NILG showed higher expression of Pim-1 (relative expression rate [RER]=2.28; 95% confidence interval [CI], 0.183-0.764) and Pim-3 (RER=3.06; 95% CI, 0.423-0.816) compared with other lesions. IHG had lower expression of Pim-1 (RER=0.31; 95% CI, 0.401-0.844) and Pim-3 (RER=0.354; 95% CI, 0.322-0.816) and noninvasive high-grade urothelial carcinoma (NIHG) demonstrated increased expression of Pim-1 and (RER=2.09; 95% CI, 0.124-0.739) and Pim-2 (RER=1.70; 95% CI, 0.151-0.591). At least 1 Pim kinase protein was expressed at the following rates: 49% in IHG, 66% in NIHG, and 76% in NILG. CONCLUSION: A high percentage of urothelial carcinomas express Pim kinases. Pim expression differs in NILG, NIHG, and IHG lesions. PMID- 26551339 TI - The Clinicopathologic Spectrum of Rapidly Progressive Glomerulonephritis Based on Glomerular Immune Deposition and Antineutrophil Cytoplasmic Antibody. AB - Rapidly progressive glomerulonephritis presents crescentic glomerulonephritis (CrGN) pathologically. Immune complex (IC)-mediated CrGN is characterized by glomerular IC deposits, whereas pauci-immune CrGN is characterized by presence of antineutrophil cytoplasmic antibody (ANCA) and absence of glomerular IC deposits. CrGN cases presenting both IC deposits and ANCA were common. We retrospectively investigated 91patients with rapidly progressive glomerulonephritis, including 36 patients with idiopathic IC-mediated CrGN and 55 patients with pauci-immune CrGN. On the basis of ANCA and IC deposits, there were 42 patients with ANCA alone (ANCA+IC-), 6 patients with IC deposits alone (ANCA-IC+), 30 patients with both ANCA and IC deposits (ANCA+IC+), and 13 patients with neither ANCA nor IC deposits. The patients with IC-mediated CrGN had more proteinuria, lower estimated glomerular filtration rate (eGFR), higher percentage of cellular crescent formation, and a worse renal outcome compared with those with pauci immune CrGN. The ANCA+IC+ CrGN patients had lower eGFR level, higher percentage of crescent formation and a tendency of more proteinuria, and worse renal outcome compared with ANCA+IC- CrGN patients, but had no significant differences on the above characteristics compared with ANCA-IC+ CrGN patients. Within a median 7.1 months, 22 patients developed end-stage renal disease. Cox regression revealed the factors including lower eGFR level, more proteinuria, lower platelet level, higher glomerular global sclerosis rate, and glomerular IgG deposits were the independent factors for worse renal outcome. In conclusion, the clinicopathologic spectrum of ANCA+IC+ CrGN was similar with IC-mediated CrGN and glomerular IgG deposition was one of the independent factors for worse renal outcome. PMID- 26551341 TI - Novel Clonal der(9)t(5;9)(q31;q34) Cytogenetic Translocation in a Giant Cell Tumor of Bone. AB - Giant cell tumor of the bone (GCTB) is a benign but locally aggressive neoplasm of long bones with higher chances of local recurrence. Many cytogenetic studies have reported clonal telomeric associations with GCTB. Here, we report for the first time a novel clonal translocation, der(9)t(5;9)(q31;q34), in a 25-year-old male patient with GCTB in the left distal femur. The biological significance of this translocation remains to be determined. PMID- 26551342 TI - Meroterpenoids from a Tropical Dysidea sp. Sponge. AB - Six new meroterpenoids (1-6), along with arenarol (7), a known rearranged drimane sesquiterpene hydroquinone, were isolated from a Dysidea sp. sponge collected from the Federated States of Micronesia. On the basis of the results of combined spectroscopic analysis, compound 1 was determined to be the cyclic ether derivative of 7, whereas 2 and 3 were assigned as the corresponding sesquiterpene quinones containing taurine-derived substituents. Compounds 4-6 possess a novel tetracyclic skeleton formed by a direct linkage between the quinone and sesquiterpene moieties. The configurations of these new compounds were assigned on the basis of combined NOESY and ECD analysis. These compounds exhibited cytotoxic and antimicrobial activities and weak inhibition against Na(+)/K(+) ATPase. PMID- 26551343 TI - Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery. AB - Branched poly(ethylenimine) (PEI) 25 kDa is an efficient gene delivery vector with outstanding gene condensation ability and great endosome escape activity. However, it also induces higher cytotoxicity. Transfection efficiency and toxicity of PEI are highly dependent upon their molecular weight and structure. We developed a bioreducible poly(ethylenimine) (PEI (-s-s-)) derived from low molecular weight PEI (1.8 kDa) for efficient gene delivery. Bioreducible core molecule is expected to increase molecular weight and reduce the cytotoxicity of the copolymer. PEI (-s-s-) polyplexes showed higher transfection efficiency and lower cytotoxicity compared to branched PEI 25 kDa, Lipofectamine(r) 2000 and, FuGENE(r) 6. In addition, PEI (-s-s-) derivative (16 kDa) formed stable polyplexes with a zeta-potential value of +34 mV and polyplex size of 61 nm. PEI (-s-s-) derivative (16 kDa) showed excellent transfection efficiency: 3.6 times higher than branched PEI 25 kDa in HeLa cells and 7.4 times higher than Lipofectamine(r) 2000 in H9C2 cell. The derivatives also showed lower cytotoxicity compared with Lipofectamine(r) 2000 and PEI 25 kDa in various cell types. In addition, newly synthesized PEI (-s-s-) derivatives have high reproducibility. PMID- 26551344 TI - Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis. AB - Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased alpha-smooth muscle actin (alpha-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis. PMID- 26551345 TI - Lipid-dendrimer hybrid nanosystem as a novel delivery system for paclitaxel to treat ovarian cancer. AB - Combining lipids and dendrimers into one formulation is an emerging platform in the drug delivery field. This study aims to (i) develop and characterize a lipid dendrimer hybrid (LDH) nanosystem for the hydrophobic anticancer drug paclitaxel, and (ii) evaluate its in vitro and in vivo anti-cancer activity in ovarian cancer models. The LDH nanosystems were prepared from 1,2-dipalmitoyl-sn-glycero-3 phosphocholine and poly (amidoamine) (PAMAM) G4.0. The size and zeta potential of the LDH nanosystem were 37.6 +/- 6.1n m and +2.9 +/- 0.1 mV, respectively, with vesicular morphology observed under cryo-TEM. The encapsulation efficiency of paclitaxel in the LDH system was 78.0 +/- 2.1%. The potency of paclitaxel could be significantly improved by 37-fold when presented in the LDH nanosystem as compared to free drug, whereby paclitaxel and PAMAM G4.0 acted synergistically in killing the ovarian cancer cells. As shown by fluorescence confocal microscopy, majority of the lipids in the LDH nanosystem were located in the plasma membrane, while the dendrimers were distributed intracellularly upon uptake. Despite the use of a 10-fold lower paclitaxel dose, the survival of IGROV-1 ovarian tumor bearing animals could be significantly prolonged by the paclitaxel-loaded LDH nanosystem, as reflected by a 50% increase in the median survival time. Such hybrid nanosystem emerged from combining two established drug delivery platforms could pave way for the development of multifunctional delivery systems for potential theranostic applications. PMID- 26551347 TI - Influence of spin multiplicity on the melting of Na55(+). AB - The influence of spin multiplicity on the melting of the Na55(+) cluster has been investigated by means of all-electron Kohn-Sham Born-Oppenheimer molecular dynamics simulations. On the basis of the quantitative agreement between the experimental and theoretical melting temperature and latent heat a detailed analysis of the cluster dynamics was performed. This analysis showed a significant structure deformation of the cluster that is inconsistent with the geometrical shell closing concept. In subsequent structure optimizations a high spin ground state in perfect icosahedral symmetry was found for the Na55(+) cluster. The Born-Oppenheimer molecular dynamics of this high-spin Na55(+) cluster indicates a particular thermal stability of the icosahedral cluster structure. A new electronic mechanism, named subshell closing, is suggested as the origin for this enhanced thermal stability of the icosahedral cluster structure. This mechanism is a natural extension of the common jellium model. By its nature, the subshell closing mechanism is general for finite systems and expected to be found in many other clusters for which the jellium model is applicable. PMID- 26551346 TI - PEG modified liposomes containing CRX-601 adjuvant in combination with methylglycol chitosan enhance the murine sublingual immune response to influenza vaccination. AB - The mucosa is the primary point of entry for pathogens making it an important vaccination site to produce a protective mucosal immune response. While the sublingual (SL) mucosa presents several barriers to vaccine penetration, its unique anatomy and physiology makes it one of the best options for mucosal vaccination. Efficient and directed delivery of adjuvants and antigens to appropriate immune mediators in the SL tissue will aid in development of effective SL vaccines against infectious diseases. Herein we demonstrate a robust immune response against influenza antigens co-delivered sublingually with engineered liposomes carrying the synthetic Toll-like receptor-4 agonist, CRX 601. Liposome modification with PEG copolymers (Pluronics), phospholipid-PEG conjugates and chitosan were evaluated for their ability to generate an immune response in a SL murine influenza vaccine model. Phospholipid-PEG conjugates were more effective than Pluronic copolymers in generating stable, surface neutral liposomes. SL vaccination with surface modified liposomes carrying CRX-601 adjuvant generated significant improvements in flu-specific responses compared with unmodified liposomes. Furthermore, the coating of modified liposomes with methylglycol chitosan produced the most effective flu-specific immune response. These results demonstrate efficient SL vaccine delivery utilizing a combination of a muco-adhesive and surface neutral liposomes to achieve a robust mucosal and systemic immune response. PMID- 26551348 TI - HYPOFRACTIONATED RADIOTHERAPY FOR MACROSCOPIC CANINE SOFT TISSUE SARCOMA: A RETROSPECTIVE STUDY OF 50 CASES TREATED WITH A 5 * 6 GY PROTOCOL WITH OR WITHOUT METRONOMIC CHEMOTHERAPY. AB - Wide surgical resection or a marginal/incomplete resection followed by full course radiation therapy is the current standard of care for canine soft tissue sarcoma. The purpose of this retrospective, descriptive, bi-institutional study was to determine the effectiveness and toxicity of a hypofractionated 5 * 6 Gy protocol on macroscopic canine soft tissue sarcoma in terms of progression-free interval (PFI) and overall survival (OS), and to identify prognostic factors for patient outcome. Dogs with macroscopic soft tissue sarcoma irradiated with 5 * 6 Gy were eligible for the study. Progression-free interval and OS were compared with respect to different tumor and patient characteristics by the Kaplan-Meier method and multivariable Cox regression analysis. Fifty dogs with macroscopic disease were included. All dogs received the same radiation therapy protocol; part of the group (n = 20) received postradiation metronomic chemotherapy. Median PFI for all cases was 419 days (95% confidence interval (CI): 287-551) and median OS was 513 days (95% CI: 368-658). Dogs with tumors on the limbs had significantly longer PFI and OS, compared with head or trunk. Increasing tumor burden decreased OS. The addition of metronomic chemotherapy yielded a significantly longer OS (757 days (95% CI: 570-944) compared with dogs that did not receive systemic treatment (286 days (95% CI: 0-518), (P = 0.023)), but did not influence progression-free interval. Toxicity was low throughout all treatments. The 5 * 6 Gy radiation therapy protocol was well tolerated and provided long PFI and OS in dogs with macroscopic soft tissue sarcoma. PMID- 26551349 TI - Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma. AB - There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA-urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features. We retrieved HCC characteristic lncRNAs, lncRNA-UCA1 and lncRNA-WRAP53, based on the microarray signature profiling (released by LncRNADisease database). Quantitative reverse transcriptase polymerase chain reaction assay (RT-qPCR) was then used to evaluate the expression of selected lncRNAs in the serum of 160 participants. Furthermore, in 20 of 82 HCC cases involved in the study, we examined the expression of lncRNA UCA1 and lncRNA-WRAP53 in 20 HCC tissues and adjacent nontumor tissues and analyzed its correlation with the serum level of these lncRNAs. The prognostic significance of the investigated parameters in HCC patients was explored. We found that lncRNA-UCA1 and lncRNA-WRAP53 were significantly higher in sera of HCC than those with chronic HCV infection or healthy volunteers. Our data suggested that the increased expression of UCA1 and WRAP53 was associated with advanced clinical parameters in HCC. Of note, tissue levels of the chosen lncRNAs strongly correlate with their sera level. The combination of both lncRNAs with serum alpha fetoprotein resulted in improved sensitivity to 100%. The median follow-up period was 21.5 months. LncRNA-WRAP53 was significant independent prognostic markers in relapse-free survival. LncRNA-UCA1 and lncRNA-WRAP53 upregulation may serve as novel serum biomarkers for HCC diagnosis and prognosis. PMID- 26551350 TI - Calcium-sensing receptor (CaSR)-mediated anti-inflammatory effects of L-amino acids in intestinal epithelial cells. AB - Calcium-sensing receptor (CaSR) plays an essential role in sensing nutrients and monitoring ion balance in the human gut. However, no discovery of CaSR-mediated anti-inflammatory effect of l-amino acids (l-AAs) on the gut system has been reported. The aim of this study is to screen and identify the anti-inflammatory activity of various l-AAs in intestinal epithelial cells (IECs) and stepwise illustrate a possible molecular mechanism for anti-inflammation. We used Caco-2 and HT-29 cell lines to evaluate the anti-inflammatory activity of l-AAs and revealed that l-tryptophan (l-Trp) and l-valine (l-Val) have strong anti inflammatory activity consistent in both cell lines. l-Trp treatment (5 mM) reduced TNF-alpha-induced IL-8 secretion from HT-29 or Caco-2 cells to about 50 or 40%, respectively. l-Trp also significantly inhibited the expression of phosphorylation of JNK or IkappaBalpha to around 50% in HT-29 cells. However, the above inhibitory effects of l-Trp on inflammatory responses in TNF-alpha-induced HT-29 cells were abrogated by NPS-2143. The result of CaSR antagonist NPS-2143 pretreatment study suggests l-Trp exerts anti-inflammatory effects on IECs through CaSR activation. The involvement of beta-arrestin2 was then found to block tumor necrosis factor (TNF)-alpha-induced signaling pathways after CaSR activated by l-Trp. These results validate a novel mechanism underlying CaSR agonistic l-AAs exerting anti-inflammatory effects on human intestinal epithelia. PMID- 26551352 TI - Primary gingival squamous cell carcinoma in a xeroderma pigmentosum type C patient. PMID- 26551351 TI - Capuchin monkeys (Cebus apella) modulate their use of an uncertainty response depending on risk. AB - Metacognition refers to thinking about thinking, and there has been a great deal of interest in how this ability manifests across primates. Based on much of the work to date, a tentative division has been drawn with New World monkeys on 1 side and Old World monkeys and apes on the other. Specifically, Old World monkeys, apes, and humans often show patterns reflecting metacognition, but New World monkeys typically do not, or show less convincing behavioral patterns. However, recent data suggest that this difference may relate to other aspects of some experimental tasks. For example, 1 possibility is that risk tolerance affects how capuchin monkeys, a New World primate species, tend to perform. Specifically, it has recently been argued that on tasks in which there are 2 or 3 options, the "risk" of guessing is tolerable for capuchins because there is a high probability of being correct even if they "know they do not know" or feel something akin to uncertainty. The current study investigated this possibility by manipulating the degree of risk (2-choices vs. 6-choices) and found that capuchin monkeys used the uncertainty response more on 6-choice trials than on 2-choice trials. We also found that rate of reward does not appear to underlie these patterns of performance, and propose that the degree of risk is modulating capuchin monkeys' use of the uncertainty response. Thus, the apparent differences between New and Old World monkeys in metacognition may reflect differences in risk tolerance rather than access to metacognitive states. PMID- 26551353 TI - Pentannulation of Heterocycles by Virtue of Precious Metal Catalysis. AB - Pentannulated heterocycles are the key structural subunit of many natural and biologically active compounds. Over the last decades, many precious metal assisted pentannulations have been described as a consequence of an extensive research. This Focus Review gives an overview of precious metal-catalyzed reactions applied to the synthesis of cyclopenta-fused heterocycles in the last five years. PMID- 26551354 TI - Update on Medical Practices That Should Be Questioned in 2015. AB - IMPORTANCE: Overuse of medical care, consisting primarily of overdiagnosis and overtreatment, is a common clinical problem. OBJECTIVES: To identify and highlight articles published in 2014 that are most likely to influence medical overuse, organized into the categories of overdiagnosis, overtreatment, and methods to avoid overuse, and to review these articles and interpret them for their importance to clinical medicine. EVIDENCE REVIEW: A structured review of English-language articles in PubMed published in 2014 and a review of tables of contents of relevant journals to identify potential articles that related to medical overuse in adults. FINDINGS: We reviewed 910 articles, of which 440 addressed medical overuse. Of these, 104 were deemed most relevant based on the presentation of original data, quality of methods, magnitude of clinical effect, and number of patients potentially affected. The 10 most influential articles were selected by author consensus using the same criteria. Findings included lack of benefit for screening pelvic examinations (positive predictive value <5%), carotid artery screening (no reduction in stroke), and thyroid ultrasonography (15-fold increase in thyroid cancer). The harms of cancer screening included unnecessary surgery and complications. Head computed tomography was an overused diagnostic test (clinically significant findings in 4% [7 of 172] of head computed tomographic scans). Overtreatment included acetaminophen for low back pain, perioperative aspirin use, medications to increase high-density lipoprotein cholesterol level, stenting for renal artery stenosis, and prolonged opioid use after surgery (use >90 days in 3% [1229 of 39,140] of patients). CONCLUSIONS AND RELEVANCE: Many common medical practices should be reconsidered. It is anticipated that our review will promote reflection on these 10 articles and lead to questioning of other non-evidence-based practices. PMID- 26551356 TI - Dissociable contribution of nucleus accumbens and dorsolateral striatum to the acquisition of risk choice behavior in the rat. AB - While a growing body of research has suggested that the mesocorticolimbic dopamine systems play a key role in decision making under risk, how the nucleus accumbens (NAC) is involved in the acquisition of risk choice behavior remains unclear. This study used a T-maze task to assess risk-based decision making in which the rat was required to assess the risk by choosing to enter either a small and certain reward arm or a large but uncertain reward arm of the maze. The latter option, when chosen, resulted in provision of 2, 4, or 8 sweeten pellets with a probability (p) of 0.5, 0.25, or 0.125, respectively. Thus the latter arm provided three different conditions of reward ratio, compared to the choice of former arm, which always provided 1 pellet with p=1. This risk choice task was then run with the expected value being equality between the binary choice options. The experimental rats first received an excitoneurotoxic lesion affecting either the NAC or the dorsolateral striatum (DLS) and this was followed by post-lesion behavioral examination. The sham lesion control rats acquired a stable risk choice with regard to each reward ratio over a 10-day test. The pattern of choice behavior appeared in risk-seeking when p=0.5 to obtain 2 pellets, and was risk-averse when larger reward resulted in lower p. The NAC lesion significantly disrupted the acquisition of the aforementioned risk choice behavior and apparently shifted the choice into a risk-averse style for all three reward ratios. No such effect was observed in the rats with DLS lesions. Neither the gross motor action nor the discrimination of different reward magnitudes was impaired by the lesions affecting either the NAC or DLS as assessed by an additional experiment. These findings suggest that firstly there is heterogeneity between NAC and DLS with respect to risk-based decision making, and that secondly the NAC is involved and critical to the acquisition of behavioral choice under risk, specially when the expected value of the reward under the two choice options is equal. PMID- 26551355 TI - Noncytolytic CD8+ Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non Progressing Rhesus Macaques. AB - The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this unique phenomenon, the ability of CD8+ T cells to suppress viral replication in vitro was investigated in 16 uninfected, longitudinally in 23 SIV-infected long-term non progressing (LTNPs), and 10 SIV-infected rhesus macaques with progressing disease. An acute infection assay utilizing CD4+ cells from MHC-mismatched monkeys to avoid cytolytic responses was employed. The study has identified CNAR as a long-term stable activity that inversely correlated with plasma viral load. The activity was also detected in CD8+ cells of uninfected macaques, which indicates that CNAR is not necessarily a virus specific response but increases after SIV-infection. Physical contact between CD4+ and CD8+ cells was mainly involved in mediating viral inhibition. Loss of this activity appeared to be due to a loss of CNAR-expressing CD8+ cells as well as a reduction of CNAR-responsive CD4+ cells. In contrast, in vitro viral replication did not differ in CD4+ cells from un-infected macaques, CNAR(+) and CNAR(-) LTNPs. A role for transitional memory cells in supporting CNAR in the macaque model of AIDS was questionable. CNAR appears to represent an important part of the immune response displayed by CD8+ T cells which might be underestimated up to now. PMID- 26551357 TI - Local Climate Experts: The Influence of Local TV Weather Information on Climate Change Perceptions. AB - Individuals who identify changes in their local climate are also more likely to report that they have personally experienced global climate change. One way that people may come to recognize that their local climate is changing is through information provided by local TV weather forecasters. Using random digit dialing, 2,000 adult local TV news viewers in Virginia were surveyed to determine whether routine exposure to local TV weather forecasts influences their perceptions of extreme weather in Virginia, and their perceptions about climate change more generally. Results indicate that paying attention to TV weather forecasts is associated with beliefs that extreme weather is becoming more frequent in Virginia, which in turn is associated with stronger beliefs and concerns about climate change. These associations were strongest for individuals who trust their local TV weathercaster as a source of information about climate change, and for those who identify as politically conservative or moderate. The findings add support to the literature suggesting that TV weathercasters can play an important role in educating the public about climate change. PMID- 26551358 TI - Psychosocial Determinants of Cannabis Dependence: A Systematic Review of the Literature. AB - BACKGROUND: Many studies have examined factors associated with the first onset of cannabis use and abuse. Currently, there is relatively little research regarding conditions under which cannabis dependence is more likely to emerge. Although previous studies have examined different potential determinants of cannabis dependence, to our knowledge, a systematic review is lacking. AIMS: The study aims to identify recent findings regarding psychosocial determinants of cannabis dependence and to summarize them systematically. METHODS: A literature search in 4 databases - Embase, Medline, PsycINFO and PSYNDEX - was conducted. Searches were limited to publications between 2000 and April 2014, English and German as languages and humans as study subjects. RESULTS: Our search detected a total of 10,568 studies. Twenty-six studies finally met inclusion criteria. Consumption patterns such as a regular cannabis use independent of social context and an early onset of use (11-15 years) were correlates of cannabis dependence. Moreover, early reactions to cannabis use and coping-oriented use motives explained additional variance. Stress factors and critical life events such as parental separation and early parental death as well as mental and social conflicts have also been linked with development of cannabis dependence. Additionally, comorbid mental disorders correlated with cannabis dependence. CONCLUSION: Numerous factors were shown to have an impact on transition to cannabis dependence. In particular, a wide range of mental disorders has been linked to an elevated risk of becoming dependent. The development of a dependence syndrome seems to be associated with diverse processes, in which social, biological and intra-individual factors interact in a complex manner. Nevertheless, the link between cannabis dependence and predisposing factors could not be resolved convincingly by most studies due to methodological weaknesses regarding dependence criteria. PMID- 26551359 TI - Effects of post-mortem aging time and type of aging on palatability of low marbled beef loins. AB - The study objective was to evaluate the effect of post-mortem aging period (14 to 49days), dry vs. wet (D vs W) type of aging on the palatability of bone-in (BI) beef short loins (n=96) and boneless (BL) strip loins (n=96) possessing United States Department of Agriculture marbling scores between Slight and Small. Warner Bratzler shear force (WBSF) scores decreased linearly over time (P=0.0001). WBSF was not influenced by aging method or loin type. Aged flavor was higher for DBL than for DBI with WBL and WBI intermediate. Dry aging strip loins increase aged flavor yet did not improve beefy flavor compared to wet aging. Based on objective data and panelist's scores for tenderness, juiciness and aged flavor, a boneless, 28days wet aged strip steak, cooked to 71 degrees C would provide the best combination of eating satisfaction and value. PMID- 26551360 TI - Dexmedetomidine: A Review of a Newer Sedative in Dentistry. AB - Dexmedetomidine is a central alpha-2 agonist, similar to Clonidine, but 8 times more specific for the central alpha-2 receptor which causes sedation with minimal depression of respiration, making it safe for sedation during procedures. It is widely used in the field of medicine for many procedures especially premedication, awake intubation, and sedation of patients in intensive care units and pediatric procedural sedation. OBJECTIVE: To do a systematic review of the pharmacology, pharmacodynamics, as well as the usage of newer sedative drug- Dexmedetomidine in dentistry. STUDY DESIGN: The search for articles was conducted in Pub Med, including the articles published in English until Oct 2014. Both animal and human studies were included using the key words, "Dexmedetomidine", "Dexmedetomidine in sedation", "Dexmedetomidine in Dentistry", and "Dexmedetomidine in Pediatric dentistry". The Articles obtained were checked for their quality methodology and inference of the studies and selected for review. RESULTS: Initial search retrieved 2436 articles, out of which 44 articles were on the subject of Dexmedetomidine in dentistry. Five of which articles were on the usage of Dexmedetomidine in pediatric dentistry. These studies were included in systematic review. CONCLUSION: The study revealed that Dexmedetomidine being a new drug with its added advantages makes a better choice for sedation in dentistry. But with limited studies on Dexmedetomidine, the recommendation to use the drug exclusively is still under debate. PMID- 26551361 TI - Prosthetic Oral Rehabilitation of a Child With S-ECC: A Case Report with Histopathologic Analysis. AB - The aim of this case report is to describe the treatment planning of a young child with severe early childhood caries (S-ECC) as well as the prosthetic rehabilitation technique. A 3-year-old female child was referred to the pediatric dentistry clinic with the chief complaint of tooth pain, difficulty in eating and recurrent hospitalizations caused by dental infections. The mother reported intermittent episodes of fever and recurrent swelling of child's face. The girl presented angular cheilitis and was referred to a dietitian. The treatment plain consisted on a behavior changes in oral hygiene habits, exodontias of all primary teeth and oral rehabilitation with a prosthesis. The extracted teeth with periapical lesions were submitted to histopathologic analysis (hematoxilin and eosin staining) and revealed an inflammatory infiltrate. The aesthetic requirement of children with S-ECC has been a challenge to pediatric dentists. In the present case, the oral rehabilitation provided for the children better aesthetic, nutrition, phonation, and functional conditions. PMID- 26551362 TI - Native Language Spoken as a Risk Marker for Tooth Decay. AB - OBJECTIVE: The purpose of this study was to assess dmft, the number of decayed, missing (due to caries), and/ or filled primary teeth, of English-speaking and non-English speaking patients of a hospital based pediatric dental clinic under the age of 72 months to determine if native language is a risk marker for tooth decay. STUDY DESIGN: Records from an outpatient dental clinic which met the inclusion criteria were reviewed. Patient demographics and dmft score were recorded, and the patients were separated into three groups by the native language spoken by their parents: English, Spanish and all other languages. RESULTS: A total of 419 charts were assessed: 253 English-speaking, 126 Spanish speaking, and 40 other native languages. After accounting for patient characteristics, dmft was significantly higher for the other language group than for the English-speaking (p<0.001) and Spanish-speaking groups (p<0.05), however the English-speaking and Spanish-speaking groups were not different from each other (p>0.05). CONCLUSIONS: Those patients under 72 months of age whose parents' native language is not English or Spanish, have the highest risk for increased dmft when compared to English and Spanish speaking patients. Providers should consider taking additional time to educate patients and their parents, in their native language, on the importance of routine dental care and oral hygiene. PMID- 26551363 TI - Levels of Stress among General Practitioners, Students and Specialists In Pediatric Dentistry during Dental Treatment. AB - OBJECTIVE: To assess self-reported stress during the performance of different procedures in pediatric dentistry, according to the professional experience of the dentists. STUDY DESIGN: During the years 2010 to 2011, an anonymous survey was administered by means of an internet link, and by distribution at professional meetings of dentists . RESULTS: No statistically significant differences in stress were reported for maxilla and mandibular procedures. Placement of a rubber dam was rated as the most stressful procedure among dental students. For general practitioners and specialists, injection of local anesthesia to an anxious child was the most stressful procedure, regardless of age, sex, or years of professional experience. A negative correlation was found between years of experience and level of stress for all the procedures surveyed, but not for the use of nitrous oxide. No differences were found between male and female dentists in stress scores for any of the procedures. CONCLUSION: Higher rates of stress during operative procedures were reported among dental students than among experienced dentists. Anxiety of the pediatric patients, but not the location of the procedure: maxillary or mandibular, affected the dentists' reported level of stress. PMID- 26551364 TI - Comparison of Parental Satisfaction with Three Tooth-Colored Full-Coronal Restorations in Primary Maxillary Incisors. AB - OBJECTIVES: To evaluate and compare the parental satisfaction among resin composite strip crown, preveneered stainless steel crown (PVSSC) and the newly introduced pre-fabricated primary zirconia crown for restoring maxillary primary incisors. STUDY DESIGN: A prospective clinical study on 39 children with carious or traumatized primary maxillary incisors. They were randomly and equally distributed in three groups and received one of the full-coronal restorations. Children were recalled to evaluate and compare parental satisfaction about performance of crowns after one year through a questionnaire. RESULTS: Parents were satisfied with all three tooth colored full-coronal restoration techniques. A significant relationship was found between colour of PVSSC (p=0.003) and durability of resin strip crowns (p=0.009) with the overall parental satisfaction levels. Parents who gave poor ratings in these two variables however rated their overall acceptance levels as being satisfied. CONCLUSION: Parental overall satisfaction was highest for zirconia primary crowns followed by resin composite strip crowns and lowest satisfaction was reported for pre-veneered SSCs. Parents were least satisfied with durability of resin composite strip crowns and colour of pre-veneered stainless steel crowns. However, this did not affect their overall satisfaction with these crowns. PMID- 26551366 TI - Effect of Honey and Green Tea Solutions on Streptococcus mutans. AB - OBJECTIVES: The aim of this cross-sectional in vivo study was to assess the effect of green tea and honey solutions on the level of salivary Streptococcus mutans. STUDY DESIGN: A convenient sample of 30 Saudi boys aged 7-10 years were randomly assigned into 2 groups of 15 each. Saliva sample was collected for analysis of level of S. mutans before rinsing. Commercial honey and green tea were prepared for use and each child was asked to rinse for two minutes using 10 mL of the prepared honey or green tea solutions according to their group. Saliva samples were collected again after rinsing. The collected saliva samples were prepared and colony forming unit (CFU) of S. mutans per mL of saliva was calculated. RESULTS: The mean number of S. mutans before and after rinsing with honey and green tea solutions were 2.28* 10(8)(2.622*10(8)), 5.64 *10(7)(1.03*10(8)), 1.17*10(9)(2.012*10(9)) and 2.59*10(8) (3.668*10(8)) respectively. A statistically significant reduction in the average number of S. mutans at baseline and post intervention in the children who were assigned to the honey (P=0.001) and green tea (P=0.001) groups was found. CONCLUSIONS: A single time mouth rinsing with honey and green tea solutions for two minutes effectively reduced the number of salivary S. mutans of 7-10 years old boys. PMID- 26551365 TI - Evaluation of Solubility and Microleakage of Glass Carbomer Sealant. AB - AIM: This study was carried out to evaluate and compare solubility and microleakage of the newly introduced moisture tolerant glass carbomer sealant. STUDY DESIGN: For evaluation of solubility, 20 specimens of glass carbomer and conventional glass ionomer were prepared and immersed in artificial saliva of pH 4 and 6 for seven days. The difference between initial and final weight was calculated. For evaluation of microleakage, glass carbomer was compared with a conventional resin sealant. 20 premolar teeth indicated for orthodontic extraction were collected and divided into two groups and the respective sealants were applied. It was subjected to thermocycling and then kept immersed in methylene blue for 24 hours. Dye penetration was scored. RESULTS: The glass carbomer specimens were less soluble than the conventional glass ionomer at both pH values. There was no significant difference in the microleakage. CONCLUSION: Being moisture resistant, glass carbomer can be used as an alternative fissure sealant material; especially in young children with partially erupted teeth and where obtaining moisture control is difficult. PMID- 26551367 TI - Acquired Oral Microflora of Newborns During the First 48 Hours of Life. AB - OBJECTIVE: To compare the oral microflora of a newborn during first hours after birth and after two days, and determine whether the newborn acquires his mother's microflora during this period. STUDY DESIGN: Saliva samples were taken from 50 newborns, on their first day of life, two days after, and from their mothers. Those samples were checked for total aerobic cultivated bacteria and mutans streptococci. RESULTS: Soon after birth, most newborns lacked any of the tested microorganisms in their oral cavity. Two days later, oral microorganisms were detected. A significant correlation was found between the total aerobic cultivated bacteria counts of the mothers, and of their newborns. CONCLUSIONS: It can be assumed, that on the first 48 hours of life, the newborn gains a major part of his oral microflora from his mother. These results might shade light on a possible to control and change the acquired microflora, at the very beginning of a human's life, creating a new, but less cariogenic flora. An accurate protocol should be examine to avoid this initial transmission during these days, while the mother and her newborn are still in the hospital, and thus might be possible to reduce caries prevalence in the future. PMID- 26551368 TI - Efficiency and Reliability of Thermal and Electrical Tests to Evaluate Pulp Status in Primary Teeth with Assessment of Anxiety Levels in Children. AB - OBJECTIVE: Assessing the pulp status plays a vital role in diagnosis and treatment planning in dentistry especially in children, who may not be able to verbalize their dental symptoms. Pulp sensibility test is used as a valuable investigation to evaluate the state of pulp. The aim of this study is to assess the efficiency and reliability of thermal and electrical pulp tests in primary teeth and to rule out the anxiety level involved in each tests. STUDY DESIGN: 30 children aged between 6 to 8 years with carious primary molar teeth in need of conservative pulp therapy were included in this study. 3 tests at random were employed on each tooth which includes cold, heat, electrical pulp test. The sensitivity, specificity, positive predictive value and negative predictive value were evaluated based on the clinical visual examination on access opening and the accuracy for each test was calculated. The Facial Image Scale (FIS) was used to assess the state of dental anxiety in children due to these pulp sensibility tests. RESULTS: The highest accuracy rate was calculated for EPT (0.814) followed by cold test (0.777) and heat test (0.759). CONCLUSION: No significant association was found between the accuracy of all the three tests. (P value > 0.05). Cold test is the most reliable test due to its simplicity and ease to perform. (FIS -1.53). PMID- 26551369 TI - Dentin Optical Density in Molars Subjected to Partial Carious Dentin Removal. AB - AIM: This study aimed to evaluate changes in the optical density of dentin in primary molars with deep caries three to six months after they were subjected to partial carious dentin removal. STUDY DESIGN: This was a blind controlled, clinical therapy study. Standardized digitalized bitewing radiographs of 42 teeth were analyzed using Adobe Photoshop((r)) to quantitatively determine the gray scale of the affected dentin beneath the restoration, in comparison with healthy dentin. A mixed-effects model was used for statistical analysis. The gray tone level was considered a dependent variable; the tooth region and the time, in addition to the interaction between them, were the independent variables. Values of p < 0.05 were significant. RESULTS: During the interval between time zero and three months, the gray tone levels of affected dentin varied from 80.99 +/- 3.17 to 98.57 +/- 3.17; i.e., an estimated increase of 18 (p < 0.0001). The values for healthy dentin ranged from 118.22 +/- 3.17 to 122.02 +/- 3.17; i.e., a mean increase of four in the gray tone levels (p = 0.0003). During the interval between three and six months, both healthy and affected dentin showed similar behavior (98.57 +/- 3.17 to 103.32 +/- 3.20 and 122.02 +/- 3.7 to 126.56 +/- 3.20, respectively) (p = 0.0001). CONCLUSIONS: Significant increments were observed in the optical density of the affected dentin after three months compared to that of healthy dentin in primary molars treated using the partial carious dentin removal technique. PMID- 26551370 TI - Association of Amelogenin with High Caries Experience in Indian Children. AB - OBJECTIVE: The purpose of this study was to identify alterations in amelogenin gene that are associated with dental caries susceptibility and to develop a non invasive early screening test for caries risk. STUDY DESIGN: 60 individuals were selected for the study based on the inclusion and exclusion criteria and were divided into two groups based on DMFT score. DMFT was scored according to World Health Organization guidelines. Saliva obtained from all participants was stored in Indogenix DNA Self-Collection kits at 4 degrees C. DNA was extracted according to the manufacturer's instructions. Once the entire DNA was isolated from each sample it was put forward for PCR amplification. The amplified amelogenin gene was then run on 2% agarose gel stained with ethidium bromide. The amplified gene was processed by SSCP technique to find out the altered bands and then subjected to DNA sequencing for identification of alterations in the amino acid sequence of amelogenin gene. RESULTS: The sequencing data showed the presence of mutation. Samples showing mutation (43.3%) showed high correlation with caries (80.7%) experience which was statistically significant. CONCLUSION: Understanding the genetics of dental caries susceptibility will provide new insights into the caries process in individuals and will facilitate the development of targeted preventive strategies. PMID- 26551371 TI - Evaluation of Different Root Canal Obturation Methods in Primary Teeth Using Cone Beam Computerized Tomography. AB - OBJECTIVE: To evaluate the efficiency of 3 different obturation techniques; motor driven lentulospiral, hand held lentulospiral and reamer in primary anterior teeth and presence of voids by analyzing with CBCT. STUDY DESIGN: 60 single rooted extracted primary teeth were prepared and obturated with ZOE paste. Obturation methods were divided into three groups. GROUP I- motor driven lentulo spiral, II- hand held lentulo spiral and III- reamer. Obturated samples were scanned in CBCT machine and images were analysed for the evaluation of their quality of fill comprising presence, location and size of voids. RESULTS: At all the locations, Group II had maximum number of sites with voids when compared to other two groups. However, statistically significant intergroup differences were observed only at coronal third location (p=0.001) and overall assessment (p=0.003). Number of affected sites revealed the difference between Groups I and II be significant statistically (p=0.002) while the difference between Groups I and III and between Groups II and III was not significant statistically (p>0.05). At all the locations as well as for combined assessment, Group I had minimum mean size of the void. CONCLUSION: Motor driven lentulo spiral technique demonstrated more number of optimal fills with fewer voids when compared to hand held lentulo spiral technique and reamer. PMID- 26551372 TI - Pain Perception: Computerized versus Traditional Local Anesthesia in Pediatric Patients. AB - BACKGROUND: Local anesthetic injection is one of the most anxiety- provoking procedure for both children and adult patients in dentistry. A computerized system for slow delivery of local anesthetic has been developed as a possible solution to reduce the pain related to the local anesthetic injection. STUDY DESIGN: The present study was conducted to evaluate and compare pain perception rates in pediatric patients with computerized system and traditional methods, both objectively and subjectively. STUDY DESIGN: It was a randomized controlled study in one hundred children aged 8-12 years in healthy physical and mental state, assessed as being cooperative, requiring extraction of maxillary primary molars. Children were divided into two groups by random sampling - Group A received buccal and palatal infiltration injection using Wand, while Group B received buccal and palatal infiltration using traditional syringe. Visual Analog scale (VAS) was used for subjective evaluation of pain perception by patient. Sound, Eye, Motor (SEM) scale was used as an objective method where sound, eye and motor reactions of patient were observed and heart rate measurement using pulse oximeter was used as the physiological parameter for objective evaluation. RESULTS: Patients experienced significantly less pain of injection with the computerized method during palatal infiltration, while less pain was not statistically significant during buccal infiltration. Heart rate increased during both buccal and palatal infiltration in traditional and computerized local anesthesia, but difference between traditional and computerized method was not statistically significant. CONCLUSION: It was concluded that pain perception was significantly more during traditional palatal infiltration injection as compared to computerized palatal infiltration, while there was no difference in pain perception during buccal infiltration in both the groups. PMID- 26551373 TI - Tuberculosis of the Cheek: A Rare Presentation. AB - Tuberculosis (TB) typically attacks the lungs. The oral lesions either primary or secondary are rarely seen and often overlooked by the clinician. More so, their atypical presentations make the diagnosis challenging; especially when they are present before the systemic symptoms become apparent. We report a case of primary tuberculosis in a 4 year old female child in a very uncommon location, the cheek. The timely diagnosis and antitubercular therapy resulted in complete resolution of the swelling within 6 months. PMID- 26551374 TI - A Retrospective Study of 248 Pediatric Oral Sedations Utilizing the Combination of Meperidine and Hydroxyzine for Dental Treatment. AB - Oral sedation for pre-cooperative and anxious pediatric patients is an important tool for the pediatric dentist. Few studies have examined the sedation regimen of meperidine and hydroxyzine. OBJECTIVES: The primary goal of this study was to evaluate the overall safety and effectiveness of the meperidine/hydroxyzine drug combination. Secondary goals included detecting potential factors that alter sedation effectiveness. STUDY DESIGN: Two hundred and forty eight electronic health records of pediatric patients (131 females, 117 males) who received meperidine/hydroxyzine sedations in a university setting were evaluated. Pediatric dental residents rated each case according to the Frankl behavioral scale and for effectiveness. Numerous factors were analyzed to evaluate their significance on overall effectiveness. Factors examined included age at time of treatment, gender, ASA status, Frankl score at various points during treatment, sextant of treatment, operator experience, dosage, use of nitrous oxide, and any complications encountered during treatment, both major and minor. RESULTS: Over 81% of sedations were considered effective or very effective. Statistically significant findings included age of patient, pre-sedation behavior, and willingness to take the medication. Less than 5% of sedations were aborted due to behavior. Only one major complication was found, which was not related to the sedation. CONCLUSIONS: Meperidine combined with hydroxyzine is a safe and effective sedation regimen for uncooperative or pre-cooperative children during dental treatment. PMID- 26551375 TI - Retrospective Study of Association between Displacement of Maxillary Canine and Tooth Agenesis. AB - OBJECTIVE: The purpose of this study was to investigate the interrelationships between displacement of maxillary canine and tooth agenesis in age from 10 to 19 years. STUDY DESIGN: The panoramic radiographs of 128 subjects with displacement of maxillary canine and 600 subjects without displacement of maxillary canine were examined. The panoramic radiographs taken between 2003 and 2013 were used for diagnosis other related dental anomalies, including permanent tooth agenesis and small maxillary lateral incisor. RESULTS: Patients with maxillary canine displacement had a significantly higher prevalence rate of permanent tooth agenesis excluding of third molars (p < 0.05). Significant increase in occurrence of tooth agenesis of maxillary lateral incisor (p < 0.05), maxillary second premolar (p < 0.05) and small maxillary lateral incisor (p < 0.05). In contrast, the mandibular second premolar did not show any significant difference (p > 0.05). CONCLUSION: This study indicates that there is positive relationship between displacement of maxillary canine, small maxillary lateral incisor and permanent tooth agenesis. Especially, maxillary lateral incisor and maxillary second premolar have strong association with maxillary canine displacement. Consequently, permanent tooth agenesis and small maxillary lateral incisor can be a predictor of maxillary canine displacement. PMID- 26551376 TI - The Many Paradoxes of Our Modern World: Is There Really an Obesity Paradox or Is It Only a Matter of Adiposity Assessment? PMID- 26551377 TI - Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis? AB - Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; 2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo. PMID- 26551378 TI - An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures. AB - Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures. PMID- 26551379 TI - Are community matrons truly invisible? PMID- 26551380 TI - Use of oral nutrition supplements in the diet of malnourished older people. PMID- 26551381 TI - Recommendations for assessing and preventing falls in adults of all ages with rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a debilitating disease that affects younger as well as older adults. It is associated with a high risk of injurious falls due to problems such as lower-limb muscle weakness, balance impairment, swollen and tender joints, pain, and fatigue. Falls are typically associated with older people; hence, many professionals do not recognise the risks for younger persons with diseases such as RA. Falls can lead to devastating consequences, such as fatalities, hip fractures (with 50% of those affected never regaining their previous level of mobility and 30% dying within 1 year), or loss of independence and confidence. Research has shown that many people are either unaware or deny their risk of falling. Therefore, it is important that health professionals, such as community nurses, are aware of the risk factors, methods of assessment, and evidence-based preventative measures, so that falls can be avoided in this population. This article presents research and practice implications for community nurses to enable them to assess, treat, and appropriately refer adults with RA who are also at risk of falls. PMID- 26551382 TI - Learning to deal with crisis in the home: Part 1--developing community simulation scenarios. AB - Contemporary health care is increasingly being located in the community. From the evident changes in demographics and general health, it can be derived that the people whom student nurses care for are likely to have multiple comorbidities and be vulnerable to clinical deterioration. These nurses are required to develop a range of transferrable skills to meet the demands of the population. The challenge for educators of preregistration student nurses is to develop educational strategies to prepare them with the skills, knowledge, and confidence necessary to recognise and manage deterioration appropriately in any context. This article is the first of two papers discussing the stimulus, design, and delivery of an educational innovation that focuses on the recognition and management of the deteriorating patient. The article explores current literature about community-focused simulation highlighting the potential learning opportunities resulting from contextualising simulation scenarios specific to the community setting. PMID- 26551383 TI - Emphasising the role of community and district nurses in Parkinson's care. PMID- 26551384 TI - 'I can't walk away': understanding the complexities in embedding a new nurse role. AB - BACKGROUND: The community matron (CM) role was introduced in England to provide a single point of access to patients living with comorbid long-term conditions who had, or were at risk of, frequent emergency hospitalisation. AIM: This study explored the factors that affected embedding of the CM role. The qualitative study was undertaken in community health services in two cities and a rural area in central England. METHOD: Participants comprised health professionals (n=30) including CMs, community service managers, and service commissioners; patients (n=10); and their family carers (n=5). RESULTS: Findings reveal that participants were largely positive about the role. However, difficulties with role setup had led to numerous changes in service delivery, which affected how the role has embedded. CONCLUSION: Many aspects of the CM role are invisible to other health professionals. Invisibility of community nursing, rather than autonomy of the CM role, seems to be a key factor in the challenges of embedding the role. PMID- 26551385 TI - Selecting appropriate absorbent products to treat urinary incontinence. AB - Urinary incontinence can have a significant negative effect on a person's life, especially if left unmanaged and untreated. Continence assessment, often carried out by community nurses, is an important element in the management of a person's urinary incontinence, and so is the selection of appropriate absorbent incontinence pads. This article reviews: the causes and effects of urinary incontinence; how to derive the most appropriate information from a continence assessment; strategies for selecting incontinence pads for a person, on the basis of the results of the continence assessment; and some of the problems and risks associated with the use of incontinence pads. PMID- 26551386 TI - Innovating in rural health in Wales: applied findings from the practitioner's perspective. AB - The demand for novel and innovative activity is commonplace in health and social care owing to multiple factors, such as ageing, lack of new resources, or the rising prevalence of long-term conditions. These factors are felt more acutely in rural communities because of a variety of influences, for example, access and a more rapidly ageing population. This study, conducted in rural Wales from 2011 to 2012, aims to explore practitioners' perceptions of the process of innovating in health and social care. A mixed-methods approach, including a questionnaire and interviews, was employed. Findings centre on the phases of innovating from generation to future activity. The lack of clarity around the term 'innovation' is found to hinder the innovation process, with risk (averseness) further stifling activity. An organisational culture of expectation and support is reported to be fundamental to initiating innovative activity. PMID- 26551387 TI - Understanding the Code: safeguarding vulnerable adults. AB - Under the provisions of the Nursing and Midwifery Council's revised Code (2015) , all district and community nurses have a professional duty to safeguard vulnerable adults from abuse. With adult abuse continuing to increase, all members of the district and community nursing teams are well placed to identify and take action to safeguard the vulnerable. In this article, Richard Griffith explains how the Care Act 2014 seeks to improve the safeguarding of vulnerable adults and the role of district and community nurses in that process. PMID- 26551388 TI - Looking at palliative care from a wider perspective. PMID- 26551389 TI - Contending with the chronicity of HIV and associated comorbidities. PMID- 26551390 TI - Learning from excellence. PMID- 26551392 TI - An effect of the substituent position and metal type on the electropolymerization properties of chalcone substituted metallophthalocyanines. AB - Cobalt(II) and manganese(III) phthalocyanines bearing peripherally and non peripherally tetra substituted {(2E)-3-[4-(dimethylamino)phenyl]prop-2 enoyl}phenoxy groups were synthesized by cyclotetramerization of the phthalonitrile derivatives and their electrochemical properties were examined using CV and SWV techniques for the first time. The novel compounds were characterized by using IR, (1)H-NMR, (13)C-NMR, UV-Vis and MS spectral data. Cyclic and square wave voltammetry revealed well-defined metal-based and ligand based reduction processes within the complexes. Electrochemical measurements exhibit that all complexes oxidatively electropolymerized on the Pt working electrode during repetitive cyclic voltammetry measurements. This study is the first example of electropolymerization of peripherally and non-peripherally tetra chalcone substituted cobalt(II) and manganese(III) phthalocyanines. The types of the metal centers of the complexes and the position of substituents affect the character of the polymerization processes. PMID- 26551391 TI - Potential therapeutic effects of mTOR inhibition in atherosclerosis. AB - Despite significant improvement in the management of atherosclerosis, this slowly progressing disease continues to affect countless patients around the world. Recently, the mechanistic target of rapamycin (mTOR) has been identified as a pre eminent factor in the development of atherosclerosis. mTOR is a constitutively active kinase found in two different multiprotein complexes, mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the value of mTORC1 inhibition to prevent the development of atherosclerotic plaques in several animal models. Rapalog-eluting stents have also shown extraordinary results in humans, even though the exact mechanism for this anti-atherosclerotic effect remains elusive. Unfortunately, rapalogs are known to trigger diverse undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These adverse effects include dyslipidaemia and insulin resistance, both known triggers of atherosclerosis. Several strategies, such as combination therapy with statins and metformin, have been suggested to oppose rapalog-mediated adverse effects. Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine monophosphate-activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis. Intermittent regimens and dose reduction have also been proposed to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2-related side effects. PMID- 26551393 TI - Independent Control of Topography for 3D Patterning of the ECM Microenvironment. AB - Biomimetic extracellular matrix (ECM) topographies driven by the magnetic-field directed self-assembly of ECM protein-coated magnetic beads are fabricated. This novel bottom-up method allows us to program isotropic, anisotropic, and diverse hybrid ECM patterns without changing other physicochemical properties of the scaffold material. It is demonstrated that this 3D anisotropic matrix is able to guide the dendritic protrusion of cells. PMID- 26551394 TI - Redefining Blood-Pressure Targets--SPRINT Starts the Marathon. PMID- 26551395 TI - Class D beta-lactamases do exist in Gram-positive bacteria. AB - Production of beta-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to beta-lactams, the largest class of antibiotics, which have saved countless lives since their inception 70 years ago. Although several hundred efficient class D enzymes have been identified in Gram negative pathogens over the last four decades, none have been reported in Gram positive bacteria. Here we demonstrate that efficient class D beta-lactamases capable of hydrolyzing a wide array of beta-lactam substrates are widely disseminated in various species of environmental Gram-positive organisms. Class D enzymes of Gram-positive bacteria have a distinct structural architecture and employ a unique substrate-binding mode that is quite different from that of all currently known class A, C and D beta-lactamases. These enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes. PMID- 26551396 TI - Structural determinants of reductive terpene cyclization in iridoid biosynthesis. AB - The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a mechanism inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5beta-reductase are highlighted. PMID- 26551397 TI - Kindlin-2 promotes invasiveness of prostate cancer cells via NF-kappaB-dependent upregulation of matrix metalloproteinases. AB - Invasive progression is the major lethal cause of prostate cancer. In this study, we aimed to investigate the role of kindlin-2, an integrin-binding focal adhesion protein, in the regulation of invasiveness of prostate cancer. We found that downregulation of kindlin-2 using small interfering RNA (siRNA) technology significantly inhibited the invasion of PC-3 and DU-145 prostate cancer cells in a Matrigel Transwell assay. Conversely, overexpression of kindlin-2 promoted the invasiveness of prostate cancer cells. Kindlin-2 overexpression was found to activate nuclear factor (NF)-kappaB-dependent signaling and upregulate the expression of matrix metalloproteinase-9 (MMP-9) and MMP-2, whereas kindlin-2 silencing led to opposing effects on the expression of NF-kappaB and MMPs. Most importantly, kindlin-2-induced invasiveness was almost completely abolished by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB signaling) or co-transfection with MMP-9 or MMP-2 siRNA. Taken together, our data indicate that kindlin-2 promotes the invasiveness of prostate cancer cells largely through NF-kappaB-dependent upregulation of MMP-9 and MMP-2. Further studies are warranted to evaluate the significance of kindlin-2 as a therapeutic target for metastatic prostate cancer. PMID- 26551398 TI - Gene expression profile of vascular ischemia-reperfusion injury in rhesus monkeys. AB - The vascular system particularly endothelium is sensitive to ischemia-reperfusion (I/R) injury, which is a big challenge in surgical practices and many vascular disorders. In the present study, we reported the global gene expression changes in a 2-h ischemia and 4-h reperfusion injury induced in the hind limb vessels of rhesus monkeys (Macaca mulatta) using microarray technique. RESULTS: The histological results showed abnormal morphology of endothelial cells after 2-h ischemia and the hematological detection found slightly extension of coagulation time after I/R treatment. Furthermore, we found distinct alterations in gene expression patterns during I/R process. These identified genes are mostly involved in inflammation, immune response, apoptosis, and cell stress signaling pathways. The significantly up-regulated genes included IL-6, regulator of G protein signaling 8, selectin E, and metallothionein 2A, et al. Whist, the robustly down-regulated genes included NECAP endocytosis associated 2, transglutaminase 2, and fibronectin 1, et al. CONCLUSION: Our results indicate that inflammation, primarily characterized by gene expression changes of cytokines and chemokines is the most important event in the early stage of I/R injury in blood vessels. PMID- 26551399 TI - Impact of childhood emotional abuse on neocortical neurometabolites and complex emotional processing in patients with generalized anxiety disorder. AB - BACKGROUND: The rostral prefrontal cortex (RPFC) is involved in reflective thought processes such as self-knowledge and person perception. We hypothesized that childhood emotional abuse, which is disruptive of emotional regulation, would differentially impact neurometabolite concentrations of the RPFC, and related neocortical areas, in adults with generalized anxiety disorder (GAD) versus healthy controls. METHODS: GAD patients (n=16; females=11) and medically healthy volunteers (n=16; F=10) were assessed using the Childhood Trauma Questionnaire (CTQ), specifically the emotional abuse category. Proton magnetic resonance spectroscopy imaging examined 3 regions of interest (ROI) from the most rostral slice from the Duyn et al. (1993) multivoxel imaging modality: rostral prefrontal cortex (BA 10,9), premotor cortex (BA 6,8) and secondary somatosensory and associated parietal cortex (BA 5,7). Metabolites included N-acetyl-aspartate, creatine, and choline. RESULTS: GAD patients reported higher emotional abuse scores versus controls. An omnibus general linear model including 3 ROI, 3 metabolites, and laterality as dependent variables revealed a significant diagnosis by CTQ emotional abuse score interactive effect. In controls, all 3 ROI for all 3 metabolites on both sides demonstrated a significant inverse relationship with emotional abuse scores; none were significant in GAD patients. LIMITATIONS: A major limitation is the uneven distribution of emotional abuse scores between the controls and GAD patients, with GAD patients reporting higher scores. CONCLUSION: Unlike controls, GAD patients appear compromised in forming a molecular representation reflective of magnitude of childhood emotional abuse. The neurometabolites in GAD patients appear non-aligned to childhood emotional abuse, suggesting potential consequences for normative "theory of mind" processes and emotional function in certain anxiety disorders. PMID- 26551400 TI - Momentary assessment of PTSD symptoms and sexual risk behavior in male OEF/OIF/OND Veterans. AB - BACKGROUND: Post-traumatic stress disorder (PTSD) in Veterans is associated with increased sexual risk behaviors, but the nature of this association is not well understood. Typical PTSD measurement deriving a summary estimate of symptom severity over a period of time precludes inferences about symptom variability, and whether momentary changes in symptom severity predict risk behavior. METHODS: We assessed the feasibility of measuring daily PTSD symptoms, substance use, and high-risk sexual behavior in Veterans using ecological momentary assessment (EMA). Feasibility indicators were survey completion, PTSD symptom variability, and variability in rates of substance use and sexual risk behavior. Nine male Veterans completed web-based questionnaires by cell phone three times per day for 28 days. RESULTS: Median within-day survey completion rates maintained near 90%, and PTSD symptoms showed high within-person variability, ranging up to 59 points on the 80-point scale. Six Veterans reported alcohol or substance use, and substance users reported use of more than one drug. Eight Veterans reported 1 to 28 high-risk sexual events. Heightened PTSD-related negative affect and externalizing behaviors preceded high-risk sexual events. Greater PTSD symptom instability was associated with having multiple sexual partners in the 28-day period. LIMITATIONS: These results are preliminary, given this small sample size, and multiple comparisons, and should be verified with larger Veteran samples. CONCLUSIONS: Results support the feasibility and utility of using of EMA to better understand the relationship between PTSD symptoms and sexual risk behavior in Veterans. Specific antecedent-risk behavior patterns provide promise for focused clinical interventions. PMID- 26551401 TI - The microtubule-associated molecular pathways may be genetically disrupted in patients with Bipolar Disorder. Insights from the molecular cascades. AB - Bipolar Disorder is a severe disease characterized by pathological mood swings from major depressive episodes to manic ones and vice versa. The biological underpinnings of Bipolar Disorder have yet to be defined. As a consequence, pharmacological treatments are suboptimal. In the present paper we test the hypothesis that the molecular pathways involved with the direct targets of lithium, hold significantly more genetic variations associated with BD. A molecular pathway approach finds its rationale in the polygenic nature of the disease. The pathways were tested in a sample of ~ 7,000 patients and controls. Data are available from the public NIMH database. The definition of the pathways was conducted according to the National Cancer Institute (http://pid.nci.nih.gov/). As a result, 3 out of the 18 tested pathways related to lithium action resisted the permutation analysis and were found to be associated with BD. These pathways were related to Reelin, Integrins and Aurora. A pool of genes selected from the ones linked with the above pathways was further investigated in order to identify the fine molecular mechanics shared by our significant pathways and also their link with lithium mechanism of action. The data obtained point out to a possible involvement of microtubule-related mechanics. PMID- 26551402 TI - Mental health symptom severity in cannabis using and non-using Veterans with probable PTSD. AB - BACKGROUND: Posttraumatic Stress Disorder (PTSD) is a disabling illness suffered by many Veterans returning from war. Some Veterans believe that cannabis may be therapeutic for PTSD. The purpose of this study was to better understand the association between cannabis use and PTSD symptoms. METHODS: The study was a matched case-control cross-sectional evaluation of the psychiatric and sociocultural associations of cannabis use in Veterans with probable PTSD. Patient self-report measures were examined comparing cannabis users (cases) to non-users (controls) who were case-matched on age and gender. RESULTS: Results indicated that there were no significant differences between cases and controls in mean PTSD Checklist-Civilian version (PCL-C) scores (59.2 and 59.1, respectively). There was also no association between PTSD scores and frequency of cannabis use. It was also observed that cases were more likely to be non Caucasian, financially challenged, and unmarried. LIMITATIONS: The sample is a convenience sample of Veterans being referred for a clinical assessment and therefore, sampling biases may limit the generalizability of the results to other populations including Veterans not seeking health care in the Veterans Affairs (VA) system. CONCLUSIONS: The results do not support the theory that cannabis use would be associated with less severe PTSD symptoms. Results do suggest important sociocultural differences in cannabis users compared to controls. PMID- 26551403 TI - Emotional reactivity to valence-loaded stimuli are related to treatment response of neurocognitive therapy. AB - Emotional Context Insensitivity (ECI) is a psychological feature observed in depressed patients characterized by a decreased emotional reactivity when presented to positive- and negative valence-loaded stimuli. Given that fronto cingulate-limbic circuits are implicated in abnormal reactivity to valence-loaded stimuli, neurocognitive treatments engaging the prefrontal cortex may be able to modulate this emotional blunting observed in MDD. Therefore, our goal was to evaluate emotional reactivity in depressed patients before and after a combination of neurocognitive interventions that engage the prefrontal cortex (cognitive control training and/or transcranial direct current stimulation). In line with the premises of the ECI framework, before the start of the antidepressant intervention, patients showed blunted emotional reactivity after exposure to negative valence-loaded stimuli. This emotional reactivity pattern changed after 9 sessions of the intervention: positive affect decreased and negative affect increased after watching a series of negative valence-loaded stimuli (i.e. images). Interestingly, higher emotional reactivity (as indexed by a larger increase in negative affect after watching the valence-loaded stimuli) at baseline predicted reductions in depression symptoms after the intervention. On the other hand, higher emotional reactivity (as indexed by a decrease in positive affect) after the intervention was marginally associated with reductions in depression symptoms. To conclude, emotional reactivity increased after the neurocognitive antidepressant intervention and it was directly associated to the degree of depression improvement. PMID- 26551404 TI - Lighting the mood of depressed youth: Feasibility and efficacy of a 2 week placebo controlled bright light treatment for juvenile inpatients. PMID- 26551405 TI - Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression. AB - OBJECTIVE: Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCT's) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCT's. METHOD: Three authors identified RCT's from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCT's of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. RESULTS: Overall, 40 RCT's were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (beta=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (beta= 1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (beta= 1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). CONCLUSIONS: Exercise is well tolerated by people with depression and drop out in RCT's is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription. PMID- 26551406 TI - Characterizing exercise-induced feelings after one bout of exercise among adolescents with and without bipolar disorder. AB - BACKGROUND: Exercise may be a practical, non-pharmacological strategy for symptom and health management for adolescents with bipolar disorder (BD). The purpose of this study was to determine if adolescents with BD experience changes in exercise induced feelings from one bout of exercise similar to their otherwise healthy peers. METHODS: Thirty-two adolescents with BD (Age (SD)=16.91 (1.4)) and 31 healthy adolescents (Age (SD)=15.68 (1.76)) completed the Exercise-Induced Feeling Inventory (EFI) before and after a 20-min bout of moderate intensity exercise (heart rate goal of 60-80% of the age estimated maximum [220 - 0.7*age]) on a cycle ergometer. Repeated-Measures ANCOVA was conducted on the four EFI subscales, controlling for age and BMI. RESULTS: There were no significant between-group differences on any subscales. An increase in Physical Exhaustion was of negligible effect size in both groups (BD: d=0.05; CONTROL: d=0.16). There was an improvement in Revitalization (BD: d=0.49; CONTROL: d=0.61) and a reduction in Tranquility (BD: d=-0.33; CONTROL: d=-0.29) post-exercise of moderate and small effect size, respectively. The control group reported an increase in Positive Engagement that was of small-to-medium effect size, (d=0.41) with negligible change in the BD group (d=0.17). Healthy adolescents reported a significantly greater tolerance for high intensity exercise than adolescents with BD. LIMITATIONS: Emotions were only assessed at two time points. CONCLUSIONS: Adolescents with BD experience similar exercise-induced emotional benefits as their healthy peers. Experimental research is needed to examine the role of exercise as a strategy to regulate mood-related symptoms. PMID- 26551407 TI - The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: A systematic review and meta-analysis. AB - BACKGROUND: A number of randomised controlled trials report a beneficial effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on emotional lability (EL) and related domains (e.g. oppositional behaviour, conduct problems). Given that n-3 PUFA supplementation shows a significant effect on reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) and that EL and related behaviours commonly co-occurs with ADHD, it is important that there is a more conclusive picture as to the effect of n-3 PUFA on these co-occurring clinical domains. METHODS: Databases (Ovid Medline, Embase, Psychinfo) were searched for trials assessing the effects of n-3 PUFA on EL, oppositional behaviour, aggression and conduct problems. We included trials in children who had ADHD or a related neurodevelopmental disorder. RESULTS: Of the 1775 identified studies, 10 were included in the meta-analysis. In the primary analyses n-3 PUFA supplementation did not show improvements in measures of EL, oppositional behaviour, conduct problems or aggression. However subgroup analyses of higher quality studies and those meeting strict inclusion criteria found a significant reduction in EL and oppositional behaviour. LIMITATIONS: A number of treatment effects may have failed to reach statistical significance due to small sample sizes and within and between study heterogeneity in terms of design and study participants. CONCLUSIONS: These results exclude the possibility of moderate to large effects. They provide suggestive evidence of small effects of n 3 PUFA on reducing EL and oppositional behaviour in subgroups of children with ADHD. PMID- 26551409 TI - US experience with recombinant factor VIIa for surgery and other invasive procedures in acquired haemophilia: analysis from the Hemostasis and Thrombosis Research Society Registry. AB - INTRODUCTION: Acquired haemophilia (AH) is a rare disorder caused by autoantibodies against factor VIII. AIM: The Hemostasis & Thrombosis Research Society (HTRS) Registry was used to monitor the safety of recombinant FVII (rFVIIa). This study aims to report data from the HTRS Registry regarding safety and efficacy of rFVIIa for haemostatic management of surgeries and other invasive procedures in patients with AH. METHODS: For each rFVIIa-treated procedure, the initial dose, total dose, average infused dose, number of doses and treatment duration were calculated. Efficacy was assessed on a 4-point scale. RESULTS: Of 166 registered patients with AH, 37 patients underwent 58 procedures [30 (51%) rFVIIa-treated]. The median (range) age of all patients undergoing procedures was 70 (13-93) years; for rFVIIa-treated patients, 74 (28-89) years. Approximately 67% (39/58) of all procedures were elective. Overall, the most common procedures were endoscopy (12) and central venous access device (10); rFVIIa was used preoperatively (11), postoperatively (13) and during six follow-up procedures during ongoing postoperative rFVIIa treatment. The median (range) initial dose was 90.0 (44-187) MUg kg(-1) preoperatively and 106.0 (56-270) MUg kg(-1) postoperatively. For rFVIIa-treated episodes with a reported outcome, 20 (91%) were rated excellent/good or no additional agents used and 2 (9%) were rated as poor/ineffective requiring a switch to another bypassing agent. No thromboembolic events were reported. CONCLUSIONS: Adequate haemostasis was provided for 91% of rFVIIa-treated procedures at doses largely conforming to the package insert. No safety concerns were reported. PMID- 26551410 TI - Bioaccessibility of PAHs in Fuel Soot Assessed by an in Vitro Digestive Model with Absorptive Sink: Effect of Food Ingestion. AB - We investigated the effects of changing physiological conditions in the digestive tract expected with food ingestion on the apparent bioaccessibility (Bapp) of 11 polycyclic aromatic hydrocarbons (PAHs) in a fuel soot. A previously established in vitro digestive model was applied that included silicone sheet as a third phase absorptive sink simulating passive transfer of PAHs to intestinal epithelium in the small intestine stage. The Bapp is defined as the fraction found in the digestive fluid plus sheet after digestion. We determined that Bapp was independent of gastric pH and addition of nonlipid milk representing dietary proteins and carbohydrates, whereas it increased with bile acids concentration (2.0-10 g/L), small intestinal pH (5.00-7.35), and addition of soybean oil representing dietary lipid (100% and 200% of the mean daily ingestion by 2-5 year olds in the U.S.). Bapp of PAHs increases with small intestinal pH due to the combined effects of mass transfer promotion from nonlabile to labile sorbed states in the soot, weaker sorption of the labile state, and increasingly favorable partitioning from the digestive fluid to the silicone sink. Under fed conditions, Bapp increases with inclusion of lipids due to the combined effects of mass transfer promotion from nonlabile to labile states, and increasingly favorable partitioning into bile acid micelles. Our results indicate significant variability in soot PAH bioaccessibility within the range of physiological conditions experienced by humans, and suggest that bioaccessibility will increase with coconsumption of food, especially food with high fat content. PMID- 26551408 TI - Resting-state functional network connectivity in prefrontal regions differs between unmedicated patients with bipolar and major depressive disorders. AB - BACKGROUND: Differentiating bipolar disorder (BD) from major depressive disorder (MDD) often poses a major clinical challenge, and optimal clinical care can be hindered by misdiagnoses. This study investigated the differences between BD and MDD in resting-state functional network connectivity (FNC) using a data-driven image analysis method. METHODS: In this study, fMRI data were collected from unmedicated subjects including 13 BD, 40 MDD and 33 healthy controls (HC). The FNC was calculated between functional brain networks derived from fMRI using group independent component analysis (ICA). Group comparisons were performed on connectivity strengths and other graph measures of FNC matrices. RESULTS: Statistical tests showed that, compared to MDD, the FNC in BD was characterized by more closely connected and more efficient topological structures as assessed by graph theory. The differences were found at both the whole-brain-level and the functional-network-level in prefrontal networks located in the dorsolateral/ventrolateral prefrontal cortex (DLPFC, VLPFC) and anterior cingulate cortex (ACC). Furthermore, interconnected structures in these networks in both patient groups were negatively associated with symptom severity on depression rating scales. LIMITATIONS: As patients were unmedicated, the sample sizes were relatively small, although they were comparable to those in previous fMRI studies comparing BD and MDD. CONCLUSIONS: Our results suggest that the differences in FNC of the PFC reflect distinct pathophysiological mechanisms in BD and MDD. Such findings ultimately may elucidate the neural pathways in which distinct functional changes can give rise to the clinical differences observed between these syndromes. PMID- 26551411 TI - In vivo assessment of closantel ovicidal activity in Fasciola hepatica eggs. AB - Anthelmintic resistance in livestock parasites is currently a worldwide problem. Fasciola hepatica is a cosmopolitan parasite which causes considerable loss in sheep and cattle production systems all over the world. Chemotherapy is currently the main tool available for its control. The intensive use of triclabendazole, the drug of choice for more than 20 years, has resulted in the development of resistant strains. The therapeutic options are adulticides such as closantel (salicylanilide anthelmintic that binds extensively to plasma albumin) to treat chronic fascioliasis in sheep, and cattle. In the present work, an Egg Hatch Assay (EHA) and morphometric studies were used to evaluate in vivo the ovicidal activity and morphology F. hepatica eggs, recovered from closantel treated sheep collected at different time intervals post treatment. Statistically significant differences (p < 0.0001) were observed in egg morphometry between the control and the treated groups in all the parameters studied. Eggs recovered from treated animals tend to be narrower and longer. Significant differences were found in the embryonation and hatching of eggs between 36 h post treatment (32, 5%) vs. approximately 85% in control, 12 h and 24 h post treatment. Our results confirm that closantel affects in vivo the normal development of the eggs. As one of the first effects, this drug affects the performance of the trematode's reproductive physiology. Even though closantel treated animals may still eliminate eggs in the first days post treatment, these are not viable. PMID- 26551412 TI - Immunization with Neospora caninum profilin induces limited protection and a regulatory T-cell response in mice. AB - Profilins are actin-binding proteins that regulate the polymerization of actin filaments. In apicomplexan parasites, they are essential for invasion. Profilins also trigger the immune response of the host by activating TLRs on dendritic cells (DCs), inducing the production of pro-inflammatory cytokines. In this study we characterized for the first time the immune response and protection elicited by a vaccine based on Neospora caninum profilin in mice. Groups of eight BALB/c mice received either two doses of a recombinant N. caninum profilin expressed in Escherichia coli. (rNcPRO) or PBS, both formulated with an aqueous soy-based adjuvant enriched in TLR-agonists. Specific anti-profilin antibodies were detected in rNcPRO-vaccinated animals, mainly IgM and IgG3, which were consumed after infection. Splenocytes from rNcPRO-immunized animals proliferated after an in vitro stimulation with rNcPRO before and after challenge. An impairment of the cellular response was observed in NcPRO vaccinated and infected mice following an in vitro stimulation with native antigens of N. caninum, related to an increase in the percentage of CD4+CD25+FoxP3+. Two out of five rNcPRO-vaccinated challenged mice were protected; they were negative for parasite DNA in the brain and showed no histopathological lesions, which were found in all PBS-vaccinated animals. As a whole, our results provide evidence of a regulatory response elicited by immunization with rNcPRO, and suggest a role of profilin in the modulation and/or evasion of immune responses against N. caninum. PMID- 26551413 TI - Protective effect of chorioamnionitis on the development of bronchopulmonary dysplasia triggered by postnatal systemic inflammation in neonatal rats. AB - BACKGROUND: Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model. METHODS: One microgram of lipopolysaccharide (LPS) or vehicle was injected into the amniotic sacs 2 d before delivery (E20). After birth, 0.25 mg/kg of LPS or vehicle was injected into the peritoneum of pups on postnatal day (P)1, P3, and P5. On P7 and P14, peripheral blood (PB), bronchoalveolar lavage fluid (BALF), and lung tissue were obtained and analyzed. RESULTS: Postnatal i.p. injections of LPS significantly increased neutrophil counts in PB and BALF on P7 and P14. Similarly, proinflammatory cytokine and angiogenic factor transcript levels were increased in the lung by i.p. LPS on P7. Alveolar and pulmonary vascular development was markedly disrupted by i.p. LPS on P14. However, pretreatment with i.a. LPS significantly negated the detrimental effects of postnatal i.p. LPS on PB and BALF neutrophil counts and on lung proinflammatory cytokine expression and histopathological changes. CONCLUSION: Exposure to early postnatal systemic LPS induces BPD, an arrest in alveolarization, in neonatal rats. Preceding exposure to i.a. LPS protects the lungs against BPD triggered by postnatal systemic inflammation. PMID- 26551415 TI - Risk of secondary solid malignancies after allogeneic hematopoietic stem cell transplantation and preventive strategies. AB - The risk of secondary solid malignancies is increased after allogeneic hematopoietic stem cell transplantation (HSCT). The risk starts at about 10 years after HSCT and continues even 20 years later. The most common secondary malignancies include squamous cell carcinoma of skin, genitourinary tract and oral cavity; lung and breast cancers. The use of total body irradiation or conditioning chemotherapy, chronic graft-versus-host disease and duration since HSCT can influence the risk of secondary solid malignancies. Secondary solid malignancies are common causes of nonrelapse mortality in long-term survivors and may account for up to 10% of late deaths. Avoiding smoking, alcohol use and excess sun exposure may reduce the risk. Cancer prevention guidelines are largely consensus-driven and follow the recommendations for general population. PMID- 26551414 TI - Systematic revision of the adeleid haemogregarines, with creation of Bartazoon n. g., reassignment of Hepatozoon argantis Garnham, 1954 to Hemolivia, and molecular data on Hemolivia stellata. AB - Life cycles and molecular data for terrestrial haemogregarines are reviewed in this article. Collection material was re-examined: Hepatozoon argantis Garnham, 1954 in Argas brumpti was reassigned to Hemolivia as Hemolivia argantis (Garnham, 1954) n. comb.; parasite DNA was extracted from a tick crush on smear of an archived slide of Hemolivia stellata in Amblyomma rotondatum, then the 18S ssrRNA gene was amplified by PCR. A systematic revision of the group is proposed, based on biological life cycles and phylogenetic reconstruction. Four types of life cycles, based on parasite vector, vertebrate host and the characteristics of their development, are defined. We propose combining species, based on their biology, into four groups (types I, II, III and IV). The characters of each type are defined and associated with a type genus and a type species. The biological characters of each type are associated with a different genus and a type species. The phylogenetic reconstruction with sequences deposited in the databases and our own new sequence of Hemolivia stellata is consistent with this classification. The classification is as follows: Type I, Hepatozoon Miller, 1908, type species H. perniciosum Miller, 1908; Type II, Karyolysus Labbe, 1894, type species K. lacertae (Danilewsky, 1886) Reichenow, 1913; Type III Hemolivia Petit et al., 1990, type species H. stellata, Petit et al., 1990; and Type IV: Bartazoon n. g., type species B. breinli (Mackerras, 1960). PMID- 26551416 TI - Three new serotypes of Rhodococcus equi in Prescott's serotyping system - Short communication. AB - Three new serotypes were found among Rhodococcus equi strains, which could not be assigned into any of the seven serotypes of Prescott's system. Fortythree R. equi strains out of 44 previously nontypable ones isolated in Hungary could be allocated into one of the three new serotypes using the agar gel immunodiffusion (AGID) test. The three new suggested serotypes are serotype 8 (proposed reference strain: HNCMB-138003), serotype 9 (proposed reference strain: HNCMB-138004) and serotype 10 (proposed reference strain: HNCMB-138005). Hyperimmune sera produced in rabbits against the new serotypes and reference strains gave precipitation only with their homologous antigens, and no crossreactions were observed. All of the previously nontypable isolates from clinical samples of horses (lung abscesses, intestinal lymph nodes, mediastinal lymph nodes) proved to be serotype 8, while strains of serotypes 8, 9 and 10 could be isolated from nasal and rectal swabs of horses and from the soil. Serotype 9 dominated among the previously nontypable strains of swine origin. One of the previously nontypable human strains was serotype 10. This serotype was also isolated from pigs, horses and the soil. The description of the three new serotypes can help us reveal new correlations between the host species, geographical origin and serotype of R. equi isolates. PMID- 26551417 TI - Vertical transmission of Mycoplasma wenyonii in cattle, supported by analysis of the ribonuclease P RNA gene - Short communication. AB - The vertical transmission of Mycoplasma (M.) wenyonii was investigated in beef cattle raised on a farm in Japan by analysing the ribonuclease P RNA (rnpB) gene sequence using PCR. Peripheral blood samples from 17 dams infected with M. wenyonii and from their neonatal calves were collected and colostrum samples were taken from cows immediately after parturition, and subsequently the blood samples of calves were monitored continuously for three months. At birth on day 0, although no rnpB gene was detected in the colostrum of any of the dams, four (23.5%) of the 17 calves born were positive. At three months after delivery, the number of positive calves decreased to three. Although horizontal transmission by blood-feeding arthropod vectors has been basically accepted as the most common route of haemoplasma infection, these findings suggest that vertical transmission is, at least in part, another most likely route of M. wenyonii infection in cattle. PMID- 26551418 TI - Complement sensitivity and factor H binding of European Francisella tularensis ssp. holarctica strains in selected animal species. AB - Francisella tularensis is a Gram-negative bacterium, the causative agent of the zoonotic disease tularaemia. The bacterium has developed several extracellular and intracellular strategies to evade the hosts' innate and adaptive immune responses. The aims of the study were to examine complement sensitivity of wild and attenuated F. tularensis ssp. holarctica strains in animal hosts of distinct sensitivity to the bacterium, to compare the complement-evading ability of wild strains of different phylogeographic background, and to examine the role of factor H in the host-pathogen interactions. Complement sensitivity assays were carried out on various F. tularensis ssp. holarctica wild strains and on the attenuated live vaccine strain (LVS) with sera of the highly sensitive house mouse (Mus musculus), the moderately sensitive European brown hare (Lepus europaeus) and the relatively resistant cattle (Bos taurus). Specific binding of complement regulator factor H to bacterial membrane proteins was examined by Western blot assays. All wild strains interacted with the hosts' complement system and showed no significant differences in their survivability. The attenuated LVS was resistant to serum killing in mouse, but was lysed in the sera of hare and cattle. Direct binding of factor H to F. tularensis membrane proteins was not detected. PMID- 26551419 TI - Vaccine potential of a nonflagellated, virulence-plasmid-cured (fliD-, pSEVDelta) mutant of Salmonella Enteritidis for chickens. AB - The aim of these studies was to assess residual virulence and early protective capacity of a negatively markered live attenuated vaccine candidate Salmonella Enteritidis mutant against a highly virulent S. Enteritidis strain using a dayold chicken model. Nonflagellated FliD negative mutants of Salmonella Enteritidis 11 (SE11) with and without the virulence plasmid proved to be sufficiently attenuated (limited invasiveness in vitro/in vivo) without reduced ability to colonise chicken gut. The early protective activity of a nonflagellated, virulence-plasmidcured (fliD-, pSEVDelta) mutant against organ invasion, caecal colonisation and faecal shedding by the highly virulent challenge strain S. Enteritidis 147 Nal(R) proved to be effective and safe. The innate and adaptive immunity was demonstrable during the first four weeks of life, and the serological response was clearly distinguishable from the response induced by the wild parental strain. In conclusion, we provided data for the first time about a virulence-plasmid-cured, nonflagellated mutant of S. Enteritidis to serve as a basis for development of a negatively markered potential live oral vaccine against virulent S. Enteritidis in chicken. PMID- 26551420 TI - Pregnancy-associated changes of serum biochemical values in Lipizzaner broodmares. AB - The aims of this study were to detect physiological changes in blood biochemical parameters throughout gestation, to compare the findings in nonpregnant and pregnant Lipizzaner mares in early-mid and late pregnancy, and to provide reference values for clinical chemistry parameters in this horse breed. A total of 136 venous blood samples were collected from 20 pregnant and 10 nonpregnant (control) asymptomatic Lipizzaner broodmares for biochemical analyses. Twelve parameters (albumin, total protein, urea, triglycerides, glucose, creatinine, alkaline phosphatase, aspartate transaminase, glutamate dehydrogenase, gammaglutamyltransferase, creatine kinase and lactate dehydrogenase) were measured. For the statistical analyses, correlation, analysis of variance and Kruskal-Wallis H-test were used to evaluate the possible associations between parameters. Serum triglyceride levels proved to be significantly different in pregnant mares compared to the control group. Total protein and urea levels significantly decreased, while glucose, triglyceride and glutamate dehydrogenase values increased from approx. the fifth month of gestation until parturition. Four biochemical parameters (albumin, aspartate transaminase, total protein and urea) were lower and three other variables (glucose, alkaline phosphatase and creatinine) were significantly higher in late-term pregnant mares than in mares in early or mid-gestation. It is concluded that reference values not only reflect the species, breed and sex but also the reproductive status of animals. PMID- 26551421 TI - Comparison of a qualitative canine C-reactive protein test to a quantitative test and traditional markers of inflammation - Short communication. AB - Qualitative tests for C-reactive protein (CRP) are available for use in dogs, and provide a rapid in-house method of detecting acute inflammation. The aim of this study was to compare results from a qualitative CRP lateral flow test (Teco CRP FASTest) to those obtained from a quantitative CRP ELISA and to traditional methods of detecting inflammation, including total leukocyte and neutrophil numbers, presence of immature neutrophils and a left shift, presence or absence of toxic changes in neutrophils and plasma fibrinogen concentration in whole blood and serum samples collected from 113 client-owned dogs. More dogs had CRP FASTest positive results than had quantitatively increased CRP (ELISA) or increases in traditional methods used for measuring inflammation. Few dogs had increases in markers of inflammation but no elevated CRP. The qualitative CRP FASTest was found to be a sensitive test for detecting increased CRP concentration and was positive more frequently than were traditional markers of inflammation. PMID- 26551422 TI - Characteristics of urolithiasis in the dog population of Hungary from 2001 to 2012. AB - The objective of this study was to describe the epidemiology of canine urolithiasis in Hungary in order to determine the annual incidence of urolithiasis and to identify breeds at risk for different types of urolithiasis. Data of a total of 2,543 canine uroliths analysed in the laboratory of the Budapest Urolith Centre were evaluated retrospectively from 2001 to 2012. Logistic regression was used to assess odds ratios for the proportion of each affected breed compared to those of crossbreeds. The annual incidence of urolithiasis was evaluated by the number of submissions compared to the estimated number of dogs in the population from which the samples originated. Epidemiologic data revealed a relatively high and increasing proportion of struvite urolithiasis. Statistical analysis of breed predispositions resulted in the detection of breeds not having been reported at risk (e.g. Bernese Mountain dog - struvite, Bichon Frise, Bolognese, Tibetan Terrier - purine, French Bulldog - cystine). Conflicting results were revealed for some other breeds previously described as being affected by certain types of urolithiasis (Chihuahua, Pekingese, Shih Tzu, English Cocker Spaniel). Regardless of the type of urolithiasis, its average cumulative incidence in the dog population of Hungary was found to be 1.76/10,000/year. PMID- 26551423 TI - Coxiella burnetii antibody dynamics in heifers born to vaccinated versus non vaccinated dams in a chronically infected dairy herd. AB - This study was designed to compare Coxiella burnetii antibody dynamics in heifers born to vaccinated or non-vaccinated dams in a single high-producing dairy herd chronically infected with the bacterium. Antibody dynamics were examined from birth to the postpartum period in replacement heifers (n = 14) born to non vaccinated dams (n = 7) or to dams that had been vaccinated on gestation days 171 177 (n = 7) and 192-198. Samples of blood, milk, faeces, vaginal fluid, colostrum and cotyledons (the latter two only at parturition) were obtained in the dams over the period from gestation days 171-177 to postpartum days 91-97. Blood samples were used to detect antibodies against C. burnetii and remaining samples for PCR identification of the bacterium. In their calves/heifers, blood samples for antibody determinations were collected from birth to postpartum at the time points 1-7 and 22-28 days and 3, 6 and 12 months of age; 90-96 and 210-216 days of gestation; and 22-28 days postpartum. All calves were born seronegative for C. burnetii. Irrespective of the shedding status of their mothers (7 were C. burnetii shedders), seroconversion occurred after colostrum intake in all calves born to seropositive cows (n = 9) and in two of three vaccinated seronegative dams. Thereafter antibody titres gradually declined and by 6 months of age all calves were seronegative. Seronegativity persisted until their first postpartum period. These findings indicate that cows vaccinated during advanced pregnancy transfer immunity to their calves via the colostrum. Maternal C. burnetii antibodies in calves persisted for three months in calves born both to seronegative vaccinated and seropositive dams. PMID- 26551424 TI - First record of Ixodes ariadnae in Germany - Short communication. AB - A long-legged tick was collected from a hibernating greater mouse-eared bat (Myotis myotis) in Baden-Wurttemberg, Germany. Based on morphological characteristics as well as on partial COI and 16S rDNA gene sequences the tick was identified as an engorged female of Ixodes ariadnae. The greater mouseeared bat is a new host record for this tick species. Taking into account the geographical position of the collection site and the known migration distance of the greater mouse-eared bat, the present data suggest the autochthonous occurrence of I. ariadnae in Germany. This is the first record of I. ariadnae in Germany, and in any country other than Hungary, where this species has been recently discovered. PMID- 26551425 TI - Treatment of naturally acquired demodectic mange with amitraz in two harbour seals (Phoca vitulina). AB - Two male harbour seals (Phoca vitulina; 33 and 35 years old, respectively), housed since 2002 at a zoo for exhibition purposes, developed severe, multifocal and diffuse skin lesions. Skin scrapings and microscopy for parasites as well as pure cultures for bacteria and dermatophytes were carried out to identify the aetiological agent. Skin scrapings showed that lesions appearing on the seals were caused by an infestation of Demodex mites, which is uncommon in marine mammals, and were not due to other causative agents (parasites, bacteria or dermatophytes). Treatment with amitraz (0.01%) once a week for three weeks and with ampicillin (10 mg/kg SID per os) for six days eliminated the mites and resolved the clinical signs of demodectic mange in the harbour seals. The purpose of this report is to describe the successful treatment of naturally acquired demodectic mange with amitraz in harbour seals. PMID- 26551426 TI - Permanent prevalence of Nosema ceranae in honey bees (Apis mellifera) in Hungary. AB - Nosema ceranae is present in honey bee (Apis mellifera L.) colonies worldwide. Studies on the comparative virulence of N. ceranae and N. apis showed significant differences in individual mortality, and the prevalence of N. ceranae seems to be predominant in both the continental and the Mediterranean climate regions. This study attempted to monitor the geographical and seasonal distribution of these two Nosema species in Hungary, using a simple laboratory method. The distribution of N. ceranae and N. apis infection rates along all seasons was homogeneous (P = 0.57). In co-infected samples, the intensity of N. ceranae infection was always significantly higher than that of N. apis infection (P < 0.001). The infection rate of infected bees in exterior samples was higher than in interior samples in each season; however, the differences were not statistically significant. The species N. ceranae had been present in Hungary already in 2004. Statistical analysis of data shows that the infection level is best represented by sampling exterior bees to establish the proportion of infected bees rather than by determining the mean spore count. PMID- 26551427 TI - Correlation between bull fertility and sperm cell velocity parameters generated by computer-assisted semen analysis. AB - Motility is one of the most important characteristics associated with the fertilising ability of spermatozoa indicating their viability and structural integrity. Therefore, the examination of motility constitutes an integral part of semen analysis. Computer-assisted semen analysis (CASA) allows an accurate and objective assessment of different sperm motion characteristics with high repeatability. The aim of this study was to evaluate the different kinematic (velocity) parameters of frozen/thawed bull semen and determine if any of them could be correlated with their fertilising capability after insemination based on the achieved pregnancy rate. Ejaculates from 10 bulls were collected and frozen. The kinematic/velocity parameters of spermatozoa were measured by CASA and compared to the pregnancy results of almost 9,000 females artificially inseminated (AI) with frozen semen of any of the 10 tested bulls. The data of the experiments are summarised mainly with a focus on the effects of individual velocities (curvilinear velocity: VCL, straight-line velocity: VSL, average path velocity: VAP) on fertility rather than on the influence of progressive motility as a whole. We conclude that VAP is the most useful semen motility characteristic which has clinical relevance in the prediction of fertility. PMID- 26551428 TI - Survey indicates circulation of 4/91 and QX-type infectious bronchitis viruses in Hungary in 2014 - Short communication. AB - Understanding the epidemiology and improving vaccinal protection against the highly variable chicken infectious bronchitis virus (IBV) requires the knowledge of circulating IBV serotypes/genotypes in defined geographic areas. Accordingly, the authors initiated a survey among the major poultry producers in Hungary in order to reveal the prevailing IBV serotypes in the country. Tracheal swabs and organ samples (caecal tonsils, kidneys, and trachea) were collected from broiler, layer, and meat-type breeder flocks, and were subjected to IBV detection by virus isolation and polymerase chain reaction (PCR). The IBV-positive samples were further characterised by nucleotide sequencing and phylogenetic analysis of a portion of the S1 IBV gene. Seventeen out of the 26 submitted samples proved to be positive for IBV. Sequence analyses revealed ten 4/91 and six QX serotypes, and a single D274 type IB virus. One sample contained a mixture of QX and Massachusetts serotype viruses. Presumably most of the 4/91 and D274 type viruses were vaccine strains. The proportion of QX type viruses and their observed variation are in good agreement with the situation in a few other European countries. The detected viruses clustered largely according to their geographic origin, with a few exceptions. If updated regularly, the preliminary 'virus map' will be useful for the adjustment of vaccination protocols. PMID- 26551429 TI - Serum inoculation as a possibility for elimination of porcine reproductive and respiratory syndrome (PRRS) from a farrow-to-finish pig farm. AB - The large heterogeneity among porcine reproductive and respiratory syndrome virus (PRRSV) isolates is probably the main obstacle to its effective control using current commercial vaccines. Intentionally exposing all breeding pigs to PRRSV circulating on the farm could eliminate porcine reproductive and respiratory syndrome (PRRS) from the herd. The objective of this study was to eliminate PRRS from a farrow-to-finish pig farm by serum inoculation. The owner was acquainted with the strict biosecurity measures. Breeding pigs were immunised with serum, which was obtained from PRRSV-positive weaners from the same farm. The percent of antibody high positive breeding pigs decreased six months after serum inoculation, while 34 months after serum inoculation no more antibody high positive pigs were detected and 56.8% of breeding pigs and all other categories were free of antibodies. In the breeding herd no virus was detected during all testing while PRRSV circulated in 2-month-old weaners until 12 months after serum inoculation. Later all tested samples from weaners, growers and fatteners were negative. Herd closure and the adoption of strict biosecurity measures are essential. Serum inoculation of the breeding herd proved to be a successful measure for eliminating PRRS from this farrow-to-finish farm. PMID- 26551431 TI - TNF-alpha from hippocampal microglia induces working memory deficits by acute stress in mice. AB - The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-alpha levels were significantly elevated after acute stress, and acute stress-induced TNF-alpha was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-alpha were not elevated after acute stress. Etanercept (TNF-alpha inhibitor) recovered working memory deficits in accordance with hippocampal TNF-alpha reductions. Overall, results suggest that TNF-alpha from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. PMID- 26551430 TI - Effect of Medicaid Expansions on Health Insurance Coverage and Access to Care among Low-Income Adults with Behavioral Health Conditions. AB - OBJECTIVE: To examine the effect of Medicaid expansions on health insurance coverage and access to care among low-income adults with behavioral health conditions. DATA SOURCES/STUDY SETTING: Nine years (2004-2012) of individual level cross-sectional data from a restricted-access version of National Survey on Drug Use and Health. STUDY DESIGN: A quasi-experimental difference-in-differences design comparing outcomes among residents in 14 states that implemented Medicaid expansions for low-income adults under the Section S1115 waiver with those residing in the rest of the country. DATA COLLECTION/EXTRACTION METHODS: The analytic sample includes low-income adult respondents with household incomes below 200 percent of the federal poverty level who have a behavioral health condition: approximately 28,400 low-income adults have past-year serious psychological distress and 24,900 low-income adults have a past-year substance use disorder (SUD). PRINCIPAL FINDINGS: Among low-income adults with behavioral health conditions, Medicaid expansions were associated with a reduction in the rate of uninsurance (p < .05), a reduction in the probability of perceiving an unmet need for mental health (MH) treatment (p < .05) and for SUD treatment (p < .05), as well as an increase in the probability of receiving MH treatment (p < .01). CONCLUSIONS: The ongoing implementation of Medicaid expansions has the potential to improve health insurance coverage and access to care for low-income adults with behavioral health conditions. PMID- 26551432 TI - Sevoflurane aggregates cognitive dysfunction and hippocampal oxidative stress induced by beta-amyloid in rats. AB - AIMS: To investigate the effects of sevoflurane inhalation on beta-amyloid (Abeta)-induced cognitive disorders and hippocampal oxidative stress in rat models. MATERIALS AND METHODS: Cognitive dysfunction is induced by hippocampal injection of Abeta1-40 (10MUg in 2MUl) for 22days. To explore the effect of sevoflurane inhalation on Abeta1-40 induced cognitive disorder, two doses of sevoflurane inhalation are used: 1.3% (Abeta+S1) and 2.6% (Abeta+S2). Sham operation (Sham, for operation control), saline injection (Control, for injection control) and 30% oxygen inhalation after Abeta1-40 injection (Abeta+O2, for inhalation control) were used as controls. All rats were further tested in electrical Y-maze and Morris water maze. Serum S100beta levels, hippocampal superoxide dismutase (SOD) activity, S100beta expression and malonyldialdehyde (MDA) concentrations were further quantified. KEY FINDINGS: Rats in Abeta+O2, Abeta+S1 and Abeta+S2 groups had lower number of correct actions in the electrical Y maze task, longer escape latencies, less time exploring the original platform, elevated serum S100beta levels, depressed hippocampal SOD activity, S100beta expression and higher MDA concentrations compared to control group (p<0.05). Such difference was not significant between Abeta+S1 and Abeta+O2 rats. Rats in Abeta+S2 group, however, showed significantly impaired performances compared to those in Abeta+S1 group (p<0.05). SIGNIFICANCE: Sevoflurane (2.6%) can aggravate the Abeta-induced cognitive dysfunction, possibly via the intracerebral oxidative stress response. PMID- 26551433 TI - Predicting SGA neonates using first-trimester screening: influence of previous pregnancy's birthweight and PAPP-A MoM. AB - OBJECTIVE: Investigating the proportions of anamnestic and biochemical variables of the previous and current pregnancies for the prediction of small for gestational age (SGA) neonates in the current pregnancy. METHODS: In this observational retrospective study, 45 029 pregnancies were examined, including 3862 patients with more than one pregnancy. Odds ratios for SGA using anamnestic parameters and pregnancy-associated plasma protein A (PAPP-A) values from all pregnancies were estimated by using a logistic regression model. RESULTS: There were 2552 (5.7%) SGA neonates. Two threshold PAPP-A values were identified at 0.15 MoM and 0.33 MoM with probabilities for SGA of 23% and 17%, respectively. A previous SGA < 10th centile and a current PAPP-A MoM value < 5th centile result in odds ratios of 4.8 (95% CI: 3.5-6.5) and 3.0 (95% CI: 1.8-5.0), respectively. The parameters' combined odds ratio is 14.1 (95% CI: 3.9-50.3) with a number needed to screen of ten for one SGA neonate at a detection rate of 37%. CONCLUSION: Information on previous pregnancies affected by SGA and a current pregnancy's low PAPP-A value are reliable predictors for a SGA delivery. First trimester biochemical analysis should be maintained to detect women at risk for delivering a SGA neonate. PMID- 26551434 TI - Reprint of "Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms". AB - Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300s(-1)) and injection moulding (approximately 900s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in identifying processing conditions, polymer miscibility and plasticisation phenomena. PMID- 26551435 TI - Modeling the Role of Bulk and Surface Characteristics of Carbon Fiber on Thermal Conductance across the Carbon-Fiber/Matrix Interface. AB - The rapid heating of carbon-fiber-reinforced polymer matrix composites leads to complex thermophysical interactions which not only are dependent on the thermal properties of the constituents and microstructure but are also dependent on the thermal transport between the fiber and resin interfaces. Using atomistic molecular dynamics simulations, the thermal conductance across the interface between a carbon-fiber near-surface region and bismaleimide monomer matrix is calculated as a function of the interface and bulk features of the carbon fiber. The surface of the carbon fiber is modeled as sheets of graphitic carbon with (a) varying degrees of surface functionality, (b) varying defect concentrations in the surface-carbon model (pure graphitic vs partially graphitic), (c) varying orientation of graphitic carbon at the interface, (d) varying interface saturation (dangling vs saturated bonds), (e) varying degrees of surface roughness, and (f) incorporating high conductive fillers (carbon nanotubes) at the interface. After combining separately equilibrated matrix system and different surface-carbon models, thermal energy exchange is investigated in terms of interface thermal conductance across the carbon fiber and the matrix. It is observed that modifications in the studied parameters (a-f) often lead to significant modulation of thermal conductance across the interface and, thus, showcases the role of interface tailoring and surface-carbon morphology toward thermal energy exchange. More importantly, the results provide key bounds and a realistic degree of variation to the interface thermal conductance values at fiber/matrix interfaces as a function of different surface-carbon features. PMID- 26551437 TI - Subarachnoid Hemorrhage and Loss of Consciousness. PMID- 26551436 TI - Enhancing Protein Capture Using a Combination of Nanoyeast Single-Chain Fragment Affinity Reagents and Alternating Current Electrohydrodynamic Forces. AB - New high-performance detection technologies and more robust protein capture agents can be combined to both rapidly and specifically capture and detect protein biomarkers associated with disease in complex biological samples. Here we demonstrate the use of recently developed recombinant affinity reagents, namely nanoyeast-scFv, in combination with alternating current electrohydrodynamic (ac EHD)-induced shear forces, to enhance capture performance during protein biomarker analysis. The use of ac-EHD significantly improves fluid transport across the capture domain, resulting in enhanced sensor-target interaction and simultaneous displacement of nonspecific molecules from the electrode surface. We demonstrate this simple proof-of-concept approach for the capture and detection of Entamoeba histolytica antigens from disinfected stool, within a span of 5 min using an ac-EHD microfluidic device. Under an ac-EHD field, antigens were captured on a nanoyeast-scFv immobilized device and subsequently detected using a quantum dot conjugated antibody. This immunosensor specifically detected antigen in disinfected stool with low background noise at concentrations down to 58.8 fM with an interassay reproducibility (%RSD of n = 3) < 17.2%, and in buffer down to 5.88 fM with an interassay reproducibility (% RSD, n = 3) of 8.4%. Furthermore, antigen detection using this immunosensor was 10 times more sensitive than previously obtained with the same nanoyeast-scFv reagents in a microfluidic device employing surface-enhanced Raman scattering (SERS) detection in buffer and at least 200 times more sensitive than methods using screen printed gold electrodes in disinfected stool. We predict this rapid and sensitive approach using these stable affinity reagents may offer a new methodology to detect protein disease biomarkers from biological matrices. PMID- 26551438 TI - Quinolone-Hydroxyquinoline Tautomerism in Quinolone 3-Esters. Preserving the 4 Oxoquinoline Structure To Retain Antimalarial Activity. AB - Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silico at the yeast Qo site established a key role for the 4-oxo and N-H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4 hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated. We describe the synthesis, structure, photochemistry, and activity against multidrug-resistant P. falciparum strain Dd2 of ethyl 4-oxo-7 methylquinoline-3-carboxylate (7Me-OQE) and ethyl 4-hydroxy-5-methylquinoline-3 carboxylate (5Me-HQE), obtained from diethyl 2-[((3 methylphenyl)amino)methylene]malonate. Theoretically (B3LYP/6-311++G(d,p)), 5Me HQE and 7Me-OQE show clear preference for the hydroxyquinoline form. The difference between the lowest energy hydroxyquinoline and quinolone forms is 27 and 38 kJ mol(-1), for 5Me-HQE and 7Me-OQE, respectively. Calculations of aromaticity indexes show that in 5Me-HQE both rings are aromatic, while in the corresponding oxo tautomers the nitrogen-containing ring is essentially non aromatic. The structure of monomeric 5Me-HQE was studied using matrix isolation coupled to FTIR spectroscopy. No traces of 4-oxoquinoline tautomers were found in the experimental IR spectra, revealing that the species present in the crystal, 5Me-HQE.HCl, was lost HCl upon sublimation but did not tautomerize. Continuous broadband irradiation (lambda > 220 nm; 130 min) of the matrix led to only partial photodecomposition of 5Me-HQE (ca. 1/3). PMID- 26551439 TI - (13)C NMR Studies, Molecular Order, and Mesophase Properties of Thiophene Mesogens. AB - Three-ring mesogens with a core comprising thiophene linked to one phenyl ring directly and to the other via flexible ester are synthesized with terminal alkoxy chains to probe the mesophase properties and find the molecular order. The phenyl thiophene link in the core offers a comparison of the mesophase features with the molecular shape of the mesogen. The synthesized mesogens display enantiotropic polymesomorphism and accordingly nematic, smectic A, smectic C and smectic B mesophases are perceived depending upon the terminal chain length. For some of the homologues, monotropic higher order smectic phases such as smectic F and crystal E are also witnessed. The existence of polymesomorphism are originally observed by HOPM and DSC and further confirmed by powder X-ray diffraction studies. For the C8 homologue, high resolution solid state (13)C NMR spectroscopy is employed to find the molecular structure in the liquid crystalline phase and using the 2D SLF technique, the (13)C-(1)H dipolar couplings are extracted to calculate the order parameter. By comparing the ratio of local order of thiophene as well as phenyl rings, we establish the bent-core shape of the mesogen. Importantly, for assigning the carbon chemical shifts of the core unit of aligned C8 mesogen, the (13)C NMR measured in mesophase of the synthetic intermediate is employed. Thus, the proposed approach addresses the key step in the spectral assignment of target mesogens with the use of (13)C NMR data of mesomorphic intermediate. PMID- 26551440 TI - Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage. AB - OBJECTIVE: To evaluate whether microfluidic sperm sorters (MFSSs) allow effective recovery of sorted motile sperm without DNA damage compared with the centrifugation and swim-up procedure. DESIGN: Experimental laboratory study. All participants completed questionnaires regarding previous and/or current diseases, surgery, reproductive experiences, lifestyle factors, and date of the preceding ejaculation. SETTING: University research laboratory. PATIENT(S): Male volunteers were recruited without setting conditions. Semen samples from healthy volunteers (n = 37) were collected in sterile containers by masturbation. INTERVENTION(S): Flow cytometric measurement and sperm chromatin structure assay analysis of DNA damage after sperm preparation using MFSS and the centrifugation and swim-up procedure. MAIN OUTCOME MEASURE(S): Efficacy and efficiency of sperm preparation, correlation between sperm DNA fragmentation index (DFI) and semen parameters, and relationship between basic characteristics and DFI after the centrifugation and swim-up procedure. RESULT(S): Final sperm concentration and motility were significantly different between the centrifugation and swim-up procedure and MFSS sperm preparations. A significantly lower sperm DNA fragmentation rate was detected with MFSS compared with the centrifugation and swim-up procedure use. No correlation was observed between DFI and smoking or drinking, but significant correlations were observed between DFI and medication use and sexual abstinence duration. CONCLUSION(S): MFSSs can be used to efficiently and reliably prepare sperm compared with the centrifugation and swim-up procedure. Further research on the clinical use of MFSSs is required to evaluate the safety and usefulness of this device. PMID- 26551441 TI - Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011-2012. AB - OBJECTIVE: To assess the characteristics of IVF cycles for which preimplantation genetic diagnosis (PGD) was used and to evaluate indications for PGD and treatment outcomes associated with this procedure as compared with cycles without PGD with the data from the U.S. National ART Surveillance System. DESIGN: Retrospective cohort study. SETTING: None. PATIENT(S): Fresh autologous cycles that involved transfer of at least one embryo at blastocyst when available. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): PGD indications and age-specific reproductive outcomes. RESULT(S): There were a total of 97,069 non-PGD cycles and 9,833 PGD cycles: 55.6% were performed for aneuploidy screening (PGD Aneuploidy), 29.1% for other reasons (PGD Other), and 15.3% for genetic testing (PGD Genetic). In comparison to non-PGD cycles, PGD Aneuploidy cycles showed a decreased odds of miscarriage among women 35-37 years (adjusted odds ratio [aOR] 0.62; 95% CI, 0.45 0.87) and women >37 years (aOR 0.55; 95% CI, 0.43-0.70); and an increased odds of clinical pregnancy (aOR 1.18; 95% CI, 1.05-1.34), live-birth delivery (aOR 1.43; 95% CI, 1.26-1.62), and multiple-birth delivery (aOR 1.98; 95% CI, 1.52-2.57) among women >37 years. CONCLUSION(S): Aneuploidy screening was the most common indication for PGD. Use of PGD was not observed to be associated with an increased odds of clinical pregnancy or live birth for women <35 years. PGD for aneuploidy was associated with a decreased odds of miscarriage for women >35 years, but an increased odds of a live-birth and a multiple live-birth delivery among women >37 years. PMID- 26551442 TI - Vigorous exercise is associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure. AB - OBJECTIVE: To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. DESIGN: Cross-sectional study. SETTING: Tertiary academic institution. PATIENT(S): Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013. INTERVENTION(S): International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. MAIN OUTCOME MEASURE(S): Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). RESULT(S): The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99). CONCLUSION(S): Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity. PMID- 26551443 TI - Exposure Duration-Dependent Ovarian Recovery in Methoxychlor-Treated Mice. AB - The pesticide methoxychlor (MXC) is known to target ovarian antral follicles in the mouse. In previous in vivo studies, MXC administration for 20 days increased atresia, but did not affect female fertility immediately after dosing. Thus, we hypothesized that perhaps not enough time had elapsed between the onset of MXC induced atresia and actual follicle loss to result in reduced fertility. The current study was undertaken to determine whether MXC treatment for 20 days results in reduced antral follicle numbers and fertility at 30 and 60 days after dosing. To test this hypothesis, adult CD-1 female mice were dosed with vehicle control or MXC (64 mg/kg/day) for 20 days. At 30 and 60 days postdosing, the mice were either subjected to fertility tests or their ovaries were collected and subjected to histological evaluation of follicle numbers and atresia. The results indicate that at 30 days after the completion of dosing, MXC significantly increased atresia and reduced primordial and total follicle numbers, but did not affect fertility compared to controls. At 60 days after completion of dosing, MXC did not significantly affect fertility, follicle numbers, or atresia compared to controls. Collectively, these data indicate that the ovary may be able to recover from MXC treatment for 20 days. PMID- 26551445 TI - Effectiveness of Lactobacillus reuteri DSM 17938 for the Prevention of Nosocomial Diarrhea in Children: A Randomized, Double-blind, Placebo-controlled Trial. AB - BACKGROUND: Multiple studies of probiotics used to prevent nosocomial diarrhea have provided conflicting results. The effects likely depend on the probiotic strain and/or dosage. The aim of this study was to assess the effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri; daily dose of 1 * 10 colony forming units) for preventing nosocomial diarrhea in children. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial in 184 children, 1-48 months of age, admitted to the hospital for reasons other than diarrhea. A computer-generated randomization scheme was used to allocate participants to receive either L. reuteri (n = 91) at a daily dose of 1 * 10 colony forming units, for the duration of hospitalization, or an identical appearing placebo (n = 93). Patients, study personnel and data analysts were blinded to assignment. The primary outcome was the occurrence of nosocomial diarrhea (>=3 loose or watery stools in 24 hours that occurred >72 hours after admission). Analysis was by intention-to-treat. RESULTS: Baseline characteristics were similar in the 2 groups. Nosocomial diarrhea occurred in 13 (7.1%) children. No difference was found between the L. reuteri and the placebo groups (7/91 vs 6/93, respectively; relative risk: 1.19; 95% confidence interval: 0.43-3.27). There was also no difference between the L. reuteri and placebo groups for any of the secondary outcomes, including adverse effects. Rotavirus vaccination status had no effect on the results. CONCLUSION: L. reuteri in the dosage regimen used was not effective in preventing nosocomial diarrhea in children. PMID- 26551444 TI - [Evidence-based therapy of polycystic ovarian syndrome]. AB - Polycystic ovary syndrome is recognized as the most common hormonal and metabolic disorder likely to affect women. The heterogeneous endocrinopathy is characterized by clinical and/or biochemical hyperandrogenism, oligo- or amenorrhoea, anovulatory infertility, and polycystic ovarian morphology. The syndrome is often associated with obesity, hyperinsulinemia and adversely affects endocrine, metabolic, and cardiovascular health. The symptoms and complaint of the patients vary with age. To maximise health gain of the syndrome, adequate, evidence based effective, efficient and safe treatment is necessary. This article summarises the highest available evidence provided by studies, meta-analysis and systematic reviews about the therapeutical possibilities for treating obesity, hyperandrogenism, menstrual abnormalities, infertility and psychological problems related to polycystic ovary syndrome. PMID- 26551446 TI - Assessment of Prime-boost Vaccination Using an AS03B-adjuvanted Influenza A (H5N1) Vaccine: A Randomized Trial in Children of Three to Less Than Eighteen Years of Age. AB - BACKGROUND: Heterologous prime-boost vaccination is a pandemic response strategy utilizing subtype-matched vaccine at pandemic onset followed by strain-matched vaccine once available. Persistence of immune response and safety of influenza A (H5N1) vaccine adjuvanted with adjuvant system containing alpha-tocopherol and squalene in an oil-in-water emulsion (AS03B) were evaluated. METHODS: An open phase 3 active-controlled study (www.clinicaltrials.gov NCT01379937) assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005-H5N1-AS03B in children 3 to <18 years of age, given 6 months after 2-dose priming with A/Indonesia/05/2005-H5N1-AS03B (H5N1(2) -H5N1 group) compared with a single dose of A/turkey/Turkey/1/2005-H5N1-AS03B in unprimed subjects (hepatitis A vaccine (HAV)-H5N1 group). Hemagglutinin inhibition responses and microneutralization antibodies were assessed to 6 months after booster vaccination. RESULTS: Hemagglutinin inhibition antibody responses against A/turkey/Turkey/1/2005-H5N1 were superior in the H5N1(2)-H5N1 versus the hepatitis A vaccine-H5N1 group overall and in each age strata (3 to <10 and 10 to <18 years). Anamnestic immune responses were demonstrated against vaccine homologous/heterologous strains in the H5N1(2)-H5N1 group. Injection site pain and fever increased with consecutive doses for children <6 years (H5N1(2)-H5N1). Immune responses to vaccine-homologous/heterologous strains persisted to 6 months after booster vaccination in the H5N1(2)-H5N1 group. CONCLUSIONS: Heterologous H5N1-AS03B-adjuvanted booster vaccination in children/adolescents was immunogenic for vaccine-homologous and heterologous strains following 2-dose priming, with immune persistence for at least 6 months. Prime-boost strategies using H5N1-AS03 could be effectively employed in this age group. PMID- 26551447 TI - Absence of Bordetella pertussis Among Infants Hospitalized for Bronchiolitis in Finland, 2008-2010. AB - In 169 Finnish infants hospitalized for bronchiolitis at age <6 months in 2008 2010, nasopharyngeal aspirates were tested by polymerase chain reaction for Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with respiratory syncytial virus), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005. PMID- 26551448 TI - Virulence and Simple Sequence Repeat Marker Segregation in a Puccinia striiformis f. sp. tritici Population Produced by Selfing a Chinese Isolate on Berberis shensiana. AB - Puccinia striiformis f. sp. tritici, the causal agent of wheat stripe rust, frequently produces new races overcoming resistance in wheat cultivars. A recently identified race, V26 with virulence to Yr26 and many other stripe rust resistance genes, has a high potential to cause epidemics in China. In this study, teliospores from a single-urediniospore isolate of V26 (Pinglan 17-7) produced on the wheat line 92R137 (Yr26) were used to produce a sexual population through selfing by infecting Berberis shensiana plants under controlled conditions. One hundred and eighteen progeny isolates and the parental isolate were phenotyped for virulence/avirulence on 24 Yr gene lines of wheat. These progeny isolates were all avirulent to Yr5, Yr8, Yr15, and YrTr1 and virulent to Yr1, Yr2, Yr7, Yr9, Yr10, Yr17, Yr24, Yr25, Yr26, YrA, YrExp2, and YrV23, indicating that the parental isolate is homozygous avirulent or homozygous virulent at these loci. The progeny population segregated for avirulence to Yr6, Yr43, and YrSP at one locus (3 avirulent:1 virulent ratio); for virulence to Yr27 and Yr28 at one locus (3 virulent:1 avirulent); and for Yr4, Yr32, and Yr44 at two loci (15 virulent:1 avirulent). Among the eight segregating avirulence/virulence loci, association was found between virulence to Yr4 and Yr32, as well as between virulence to Yr6 and Yr43 based on chi(2) tests. From 82 genotypically different progeny isolates, 24 pathotypes and 82 multilocus genotypes were identified. The results show that a highly diverse population can be produced from a single isolate by selfing on a barberry plant and sexually produced population can be used to genetically characterize virulence of the stripe rust pathogen. PMID- 26551449 TI - Localization of 'Candidatus Liberibacter solanacearum' and Evidence for Surface Appendages in the Potato Psyllid Vector. AB - The potato psyllid Bactericera cockerelli is implicated as the vector of the causal agent of zebra chip of potato and vein-greening of tomato diseases. Until now, visual identification of bacteria in the genus 'Candidatus Liberibacter' has relied on direct imaging by light and electron microscopy without labeling, or with whole-organ fluorescence labeling only. In this study, aldehyde fixative followed by a coagulant fixative, was used to process adult psyllids for transmission electron microscopy (TEM) colloidal gold in situ hybridization experiments. Results indicated that 'Ca. Liberibacter solanacearum' (CLso) specific DNA probes annealed to a bacterium that formed extensive, monocultural biofilms on gut, salivary gland, and oral region tissues, confirming that it is one morphotype of potentially others, that is rod-shaped, approximately 2.5 um in diameter and of variable length, and has a rough, granular cytosol. In addition, CLso, prepared from shredded midguts, and negatively stained for TEM, possessed pili- and flagella-like surface appendages. Genes implicating coding capacity for both types of surface structures are encoded in the CLso genome sequence. Neither type was seen for CLso associated with biofilms within or on digestive organs, suggesting that their production is stimulated only in certain environments, putatively, in the gut during adhesion leading to multiplication, and in hemolymph to afford systemic invasion. PMID- 26551450 TI - Diversity of Xanthomonas campestris Isolates from Symptomatic Crucifers in New York State. AB - To assess the diversity of Xanthomonas campestris spp. infecting crucifers in New York, 154 isolates were collected over 10 years across the state. The goal was to determine if isolates of the pathogen were overwintering in New York and serving as primary inoculum in subsequent years, or if novel isolates were entering the state each year. Pure cultures of isolates were characterized using multilocus sequence analysis (MLSA), a greenhouse pathogenicity assay, repetitive element polymerase chain reaction (Rep-PCR) using the BOX-A1R primer, and enzyme-linked immunosorbent assay. The MLSA scheme proved to be more efficient than Rep-PCR for a large sample population and for comparison with global isolates. X. campestris isolated from crucifers in New York comprised of X. campestris pv. campestris and X. campestris pv. raphani, with X. campestris pv. raphani being predominately isolated from transplants. Evidence for unique haplotypes persisting on the same farm for several years due to improper seedbed rotations was documented in addition to novel haplotypes being spread throughout states through infected transplants and seed. Rep-PCR confirmed the high diversity of X. campestris and was used to generate 15 unique fingerprint patterns from isolates collected in the first 5 years. A worldwide comparison of isolates suggests that the X. campestris pv. campestris population appears to be very homogenous with dominant haplotypes persisting for extended periods and being globally disseminated. PMID- 26551451 TI - Host Transcriptional Profiling at Early and Later Stages of the Compatible Interaction Between Phaseolus vulgaris and Meloidogyne incognita. AB - The root-knot nematode (Meloidogyne incognita) is one of most devastating pathogens that attack the common bean crop. Although there is evidence that some cultivars have race-specific resistance against M. incognita, these resistance sources have not proved effective, and nematodes are able to circumvent the host's defense system. We constructed RNA-seq based libraries and used a high throughput sequencing platform to analyze the plant responses to M. incognita. Assessments were performed at 4 and 10 days after inoculation corresponding to the stages of nematode penetration and giant cell development, respectively. Large-scale transcript mapping to the common bean reference genome (G19833) resulted in the identification of 27,195 unigenes. Of these, 797 host genes were found to be differentially expressed. The functional annotation results confirm the complex interplay between abiotic and biotic stress signaling pathways. High expression levels of the wounding-responsive genes were observed over the interaction. At early response, an overexpression of the N gene, a TIR-NBS-LRR resistance gene, was understood as a host attempt to overcome the pathogen attack. However, the repression of heat shock proteins resulted in a lack of reactive oxygen species accumulation and absence of a hypersensitive response. Furthermore, the host basal response was broken by the repression of the ethylene/jasmonate pathway later in the response, resulting in a continuous compatible process with consequent plant susceptibility. PMID- 26551452 TI - Porous Hybrid Composites of Few-Layer MoS2 Nanosheets Embedded in a Carbon Matrix with an Excellent Supercapacitor Electrode Performance. AB - Porous hierarchical architectures of few-layer MoS2 nanosheets dispersed in carbon matrix are prepared by a microwave-hydrothermal method followed by annealing treatment via using glucose as C source and structure-directing agent and (NH4 )2 MoS4 as both Mo and S sources. It is found that the morphology and size of the secondary building units (SBUs), the size and layer number of MoS2 nanosheets as well as the distribution of MoS2 nanosheets in carbon matrix, can be effectively controlled by simply adjusting the molar ratio of (NH4 )2 MoS4 to glucose, leading to the materials with a low charge-transfer resistance, many electrochemical active sites and a robust structure for an outstanding energy storage performance including a high specific capacitance (589 F g(-1) at 0.5 A g(-1) ), a good rate capability (364 F g(-1) at 20 A g(-1) ), and an excellent cycling stability (retention 104% after 2000 cycles) for application in supercapacitors. The exceptional rate capability endows the electrode with a high energy density of 72.7 Wh kg(-1) and a high power density of 12.0 kW kg(-1) simultaneously. This work presents a facile and scalable approach for synthesizing novel heterostructures of MoS2 -based electrode materials with an enhanced rate capability and cyclability for potential application in supercapacitor. PMID- 26551453 TI - Segmentation of liver and spleen based on computational anatomy models. AB - Accurate segmentation of abdominal organs is a key step in developing a computer aided diagnosis (CAD) system. Probabilistic atlas based on human anatomical structure, used as a priori information in a Bayes framework, has been widely used for organ segmentation. How to register the probabilistic atlas to the patient volume is the main challenge. Additionally, there is the disadvantage that the conventional probabilistic atlas may cause a bias toward the specific patient study because of the single reference. Taking these into consideration, a template matching framework based on an iterative probabilistic atlas for liver and spleen segmentation is presented in this paper. First, a bounding box based on human anatomical localization, which refers to the statistical geometric location of the organ, is detected for the candidate organ. Then, the probabilistic atlas is used as a template to find the organ in this bounding box by using template matching technology. We applied our method to 60 datasets including normal and pathological cases. For the liver, the Dice/Tanimoto volume overlaps were 0.930/0.870, the root-mean-squared error (RMSE) was 2.906mm. For the spleen, quantification led to 0.922 Dice/0.857 Tanimoto overlaps, 1.992mm RMSE. The algorithm is robust in segmenting normal and abnormal spleens and livers, such as the presence of tumors and large morphological changes. Comparing our method with conventional and recently developed atlas-based methods, our results show an improvement in the segmentation accuracy for multi-organs (p<0.00001). PMID- 26551454 TI - Sieve-based relation extraction of gene regulatory networks from biological literature. AB - BACKGROUND: Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. RESULTS: We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming data into skip-mention sequences is appropriate for detecting relations between distant mentions. CONCLUSIONS: Linear-chain conditional random fields, along with appropriate data transformations, can be efficiently used to extract relations. The sieve-based architecture simplifies the system as new sieves can be easily added or removed and each sieve can utilize the results of previous ones. Furthermore, sieves with conditional random fields can be trained on arbitrary text data and hence are applicable to broad range of relation extraction tasks and data domains. PMID- 26551455 TI - Long non-coding MIAT mediates high glucose-induced renal tubular epithelial injury. AB - BACKGROUND AND OBJECTIVE: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury. METHODS: Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65 mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in vitro high glucose-triggered human renal tubular epithelial cell line (HK 2) was used to explore the mechanism underling MIAT regulated high glucose induced tubular damage. RESULTS: In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression. CONCLUSION: In summary, our data suggested that MIAT/Nrf2 served as an important signaling pathway for high glucose induced renal tubular epithelial injury. PMID- 26551456 TI - Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-beta peptide. AB - Aggregation of amyloid-beta (Abeta) peptides is a characteristic pathological feature of Alzheimer's disease. We have exploited the relationship between solvent exposure and intrinsic fluorescence of a single tyrosine residue, Tyr10, in the Abeta sequence to probe structural features of the monomeric, oligomeric and fibrillar forms of the 42-residue Abeta1-42. By monitoring the quenching of Tyr10 fluorescence upon addition of water-soluble acrylamide, we show that in Abeta1-42 oligomers this residue is solvent-exposed to a similar extent to that found in the unfolded monomer. By contrast, Tyr10 is significantly shielded from acrylamide quenching in Abeta1-42 fibrils, consistent with its proximity to the fibrillar cross-beta core. Furthermore, circular dichroism measurements reveal that Abeta1-42 oligomers have a considerably lower beta-sheet content than the Abeta1-42 fibrils, indicative of a less ordered molecular arrangement in the former. Taken together these findings suggest significant differences in the structural assembly of oligomers and fibrils that are consistent with differences in their biological effects. PMID- 26551457 TI - Carbonic anhydrases and their functional differences in human and mouse sperm physiology. AB - Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm. PMID- 26551458 TI - Mammalian farnesyltransferase alpha subunit regulates vacuolar protein sorting associated protein 4A (Vps4A)--dependent intracellular trafficking through recycling endosomes. AB - The protein farnesyltransferase (FTase) mediates posttranslational modification of proteins with isoprenoid lipids. FTase is a heterodimer and although the beta subunit harbors the active site, it requires the alpha subunit for its activity. Here we explore the other functions of the FTase alpha subunit in addition to its established role in protein prenylation. We found that in the absence of the beta subunit, the alpha subunit of FTase forms a stable autonomous dimeric structure in solution. We identify interactors of FTase alpha using mass spectrometry, followed by rapid in vitro analysis using the Leishmania tarentolae cell - free system. Vps4A was validated for direct binding to the FTase alpha subunit both in vitro and in vivo. Analysis of the interaction with Vps4A in Hek 293 cells demonstrated that FTase alpha controls trafficking of transferrin receptor upstream of this protein. These results point to the existence of previously undetected biological functions of the FTase alpha subunit that includes control of intracellular membrane trafficking. PMID- 26551459 TI - Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer. AB - Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer. PMID- 26551460 TI - High-affinity interaction between interleukin-11 and S100P protein. AB - Interleukin-11 (IL-11) and S100P are oncoproteins co-expressed in numerous cancers, which might favor their interaction during oncogenesis. We have explored the possibility of this interaction by surface plasmon resonance spectroscopy, intrinsic fluorescence, and chemical crosslinking. Recombinant forms of IL-11 and S100P interact with each other under physiological level of calcium ions. IL-11 molecule has at least two S100P-binding sites with dissociation constants of 32 nM and 288 nM, which is 5-13-fold lower than its affinity to extracellular domain of IL-11 receptor subunit alpha. S100P does not alter IL-11-induced STAT3 activation in HEK293 cells co-expressing IL-11 receptors, but could affect other tumorigenic signaling pathways. The highly specific IL-11 - S100P interaction occurring under physiologically relevant conditions should be taken into consideration upon development of the antineoplastics inhibiting IL-11 signaling. PMID- 26551461 TI - Temporal and organ-specific detection of cNMPs including cUMP in the zebrafish. AB - The cyclic pyrimidine nucleotides cCMP and cUMP occur in mammalian cell lines. Recently, cCMP was also identified in mouse organs. Due to technical difficulties, it has not been possible to detect cUMP in organs or tissues yet. Here, we have generated a temporal profile of the occurrence of nucleoside 3',5' cyclic monophosphates during different developmental stages of embryogenesis and in different organs of the adult zebrafish Danio rerio. Cyclic nucleotides were quantified by high performance liquid chromatography quadrupole tandem mass spectrometry. The identity of cCMP and cUMP in the zebrafish was confirmed by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. We show for the first time that cUMP can be detected during embryogenesis and in adult organs of this vertebrate model system. PMID- 26551462 TI - Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration. AB - Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease modifying therapies in SBMA. PMID- 26551463 TI - Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle. AB - Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1alpha was higher in EDL, and phospho-eIF2alpha was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging. PMID- 26551465 TI - Indomethacin-induced intestinal epithelial cell damage is mediated by pVHL activation through the degradation of collagen I and HIF-1alpha. AB - Non-steroidal anti-inflammatory drug (NSAID)-induced epithelial cell damage occurs not only in the stomach but also in the intestines and colon. Although several studies have investigated the related mechanism underlying lower gastrointestinal tract injury, the details of this mechanism are still unclear. Since it was reported that protein degradation might play an important role, herein, we focused on one of the major ubiquitin E3 ligases, the von Hippel Lindau protein (pVHL). To understand whether pVHL is involved in the observed cell damage, we examined whether indomethacin (IM) treatment affects pVHL expression in the rat IEC6 intestinal epithelial cell line. We showed that pVHL was upregulated after IM treatment through increased oxidative stress. pVHL siRNA prevented cell injury after IM treatment. Furthermore, the collagen I and HIF 1alpha protein band intensities were both decreased after IM treatment, whereas MG132 reversed the proteins' downregulation, indicating that the IM treatment induced downregulation was due to the degradation through pVHL-mediated polyubiquitination. Co-immunoprecipitation showed that pVHL interacted with both collagen I and HIF-1alpha. The degradation of collagen I and HIF-1alpha after IM treatment was reversed by siVHL or a Mn-SOD mimetic, Mn(III)TMPyP. The expression of collagen I and HIF-1alpha was correlated with pVHL expression level, whereas only HIF-1alpha, not collagen I, was upregulated after the treatment of a prolyl hydroxylase inhibitor, CoCl2. The effect of pVHL on the intestinal epithelium after IM treatment was also tested in vivo. Western blot analyses were used to test whether pVHL's protein expression level might increase after oral administration of IM to mice, and which showed that IM upregulated pVHL expression and degraded collagen I and HIF-1alpha, consistent with the data obtained in IEC6 cells. These data suggested that intestinal epithelial cells were injured after IM treatment through the pVHL overexpression-induced degradation of collagen I or HIF-1alpha. Therefore, pVHL might be a molecular target for IM-induced intestinal epithelial cell injury. PMID- 26551464 TI - Mutation of the gene encoding the ribonuclease P RNA in the hyperthermophilic archaeon Thermococcus kodakarensis causes decreased growth rate and impaired processing of tRNA precursors. AB - Ribonuclease P (RNase P) catalyzes the processing of 5' leader sequences of tRNA precursors in all three phylogenetic domains. RNase P also plays an essential role in non-tRNA biogenesis in bacterial and eukaryotic cells. For archaeal RNase Ps, additional functions, however, remain poorly understood. To gain insight into the biological function of archaeal RNase Ps in vivo, we prepared archaeal mutants KUWDeltaP3, KUWDeltaP8, and KUWDeltaP16, in which the gene segments encoding stem-loops containing helices, respectively, P3, P8 and P16 in RNase P RNA (TkopRNA) of the hyperthermophilic archaeon Thermococcus kodakarensis were deleted. Phenotypic analysis showed that KUWDeltaP3 and KUWDeltaP16 grew slowly compared with wild-type T. kodakarensis KUW1, while KUWDeltaP8 displayed no difference from T. kodakarensis KUW1. RNase P isolated using an affinity-tag from KUWDeltaP3 had reduced pre-tRNA cleavage activity compared with that from T. kodakarensis KUW1. Moreover, quantitative RT-PCR (qRT-PCR) and Northern blots analyses of KUWDeltaP3 showed greater accumulation of unprocessed transcripts for pre-tRNAs than that of T. kodakarensis KUW1. The current study represents the first attempt to prepare mutant T. kodakarensis with impaired RNase P for functional investigation. Comparative whole-transcriptome analysis of T. kodakarensis KUW1 and KUWDeltaP3 should allow for the comprehensive identification of RNA substrates for archaeal RNase Ps. PMID- 26551466 TI - Kibra and aPKC regulate starvation-induced autophagy in Drosophila. AB - Autophagy is a bulk degradation system that functions in response to cellular stresses such as metabolic stress, endoplasmic reticulum stress, oxidative stress, and developmental processes. During autophagy, cytoplasmic components are captured in double-membrane vesicles called autophagosomes. The autophagosome fuses with the lysosome, producing a vacuole known as an autolysosome. The cellular components are degraded by lysosomal proteases and recycled. Autophagy is important for maintaining cellular homeostasis, and the process is evolutionarily conserved. Kibra is an upstream regulator of the hippo signaling pathway, which controls organ size by affecting cell growth, proliferation, and apoptosis. Kibra is mainly localized in the apical membrane domain of epithelial cells and acts as a scaffold protein. We found that Kibra is required for autophagy to function properly. The absence of Kibra caused defects in the formation of autophagic vesicles and autophagic degradation. We also found that the well-known cell polarity protein aPKC interacts with Kibra, and its activity affects autophagy upstream of Kibra. Constitutively active aPKC decreased autophagic vesicle formation and autophagic degradation. We confirmed the interaction between aPKC and Kibra in S2 cells and Drosophila larva. Taken together, our data suggest that Kibra and aPKC are essential for regulating starvation-induced autophagy. PMID- 26551467 TI - A salmon DNA scaffold promotes osteogenesis through activation of sodium dependent phosphate cotransporters. AB - We previously reported the promotion of bone regeneration in calvarial defects of both normal and ovariectomy-induced osteoporotic rats, with the use of biodegradable DNA/protamine scaffold. However, the method by which this DNA containing scaffold promotes bone formation is still not understood. We hypothesize that the salmon DNA, from which this scaffold is derived, has an osteoinductive effect on pre-osteoblasts and osteoblasts. We examined the effects of salmon DNA on osteoblastic differentiation and calcification in MC3T3-E1 cells, mouse osteoblasts, in vitro and bone regeneration in a calvarial defect model of aged mouse in vivo. The salmon DNA fragments (300 bps) upregulated the expression of the osteogenic markers, such as alkaline phosphatase, Runx2, and osterix (Osx) in MC3T3E1 cells compared with incubation with osteogenic induction medium alone. Measurement of phosphate ion concentrations in cultures showed that the DNA scaffold degraded phosphate ions were released to the cell cultures. Interestingly, we found that the inclusion of DNA in osteoblastic cell cultures upregulated the expression of sodium-dependent phosphate (NaPi) cotransporters, SLC20A1 and SLC34A2, in MC3T3-E1 cells in a time dependent manner. Furthermore, the inclusion of DNA in cell cultures increased the transcellular permeability of phosphate. Conversely, the incubation of phosphonoformic acid, an inhibitor of NaPi cotransporters, attenuated the DNA-induced expression and activation of SLC20A1 and SLC34A2 in MC3T3-E1 cells, resulting in suppression of the osteogenic markers. The implantation of a salmon DNA scaffold disk promoted bone regeneration using calvarial defect models in 30-week-old mice. Our results indicate that the phosphate released from salmon DNA upregulated the expression and activation of NaPi cotransporters, resulting in the promotion of bone regeneration. PMID- 26551470 TI - What you can do to improve adult immunization rates. PMID- 26551468 TI - Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal Transplant Recipients. AB - BACKGROUND: Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new onset diabetes after transplantation (NODAT). OBJECTIVE: To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post transplant complications). METHODS: We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia. RESULTS: Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (P<0.0001) are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001), non-White race (P = 0.002), BMI (P = 0.002), HDL cholesterol (P = 0.003), uric acid (P = 0.012), and using steroid (P = 0.007) are the significant risk factors for the recurrent cases of hyperglycemia. DISCUSSION: This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature. PMID- 26551469 TI - Femtosecond Laser-Controlled Tip-to-Tip Assembly and Welding of Gold Nanorods. AB - Directed assembly of gold nanorods through the use of dithiolated molecular linkers is one of the most efficient methodologies for the morphologically controlled tip-to-tip assembly of this type of anisotropic nanocrystals. However, in a direct analogy to molecular polymerization synthesis, this process is characterized by difficulties in chain-growth control over nanoparticle oligomers. In particular, it is nearly impossible to favor the formation of one type of oligomer, making the methodology hard to use for actual applications in nanoplasmonics. We propose here a light-controlled synthetic procedure that allows obtaining selected plasmonic oligomers in high yield and with reaction times in the scale of minutes by irradiation with low fluence near-infrared (NIR) femtosecond laser pulses. Selective inhibition of the formation of gold nanorod n mers (trimers) with a longitudinal localized surface plasmon in resonance with a 800 nm Ti:sapphire laser, allowed efficient trapping of the (n - 1)-mers (dimers) by hot spot mediated photothermal decomposition of the interparticle molecular linkers. Laser irradiation at higher energies produced near-field enhancement at the interparticle gaps, which is large enough to melt gold nanorod tips, offering a new pathway toward tip-to-tip welding of gold nanorod oligomers with a plasmonic response at the NIR. Thorough optical and electron microscopy characterization indicates that plasmonic oligomers can be selectively trapped and welded, which has been analyzed in terms of a model that predicts with reasonable accuracy the relative concentrations of the main plasmonic species. PMID- 26551471 TI - Generalized, well-dispersed rash . wheal development after tactile irritation . normal vital signs . Dx? PMID- 26551472 TI - PURLs: This adjunct medication can speed CAP recovery. AB - Adding prednisone to the antibiotic regimen can help patients hospitalized with community-acquired pneumonia to stabilize more quickly and leave the hospital sooner. PMID- 26551473 TI - Rash, diarrhea, and eosinophilia. PMID- 26551474 TI - Drug-induced liver injury: Diagnosing (and treating) it early. AB - Drug-induced liver injury can have an insidious--and unpredictable--course. Left unchecked, it can progress to liver failure. This article and algorithm can facilitate prompt diagnosis and treatment. PMID- 26551475 TI - Help Desk Answers: Are overweight children likely to become overweight adults? PMID- 26551476 TI - Office visits should be a "dance," not a dictate. PMID- 26551477 TI - COPD: Optimizing treatment. PMID- 26551478 TI - Clinical Inquiry: Does high dietary soy intake affect a woman's risk of primary or recurrent breast cancer? PMID- 26551479 TI - Linear rash from shoulder to wrist. PMID- 26551480 TI - Left subconjunctival hemorrhage . renal dysfunction . international normalized ratio of 4.5 . Dx? PMID- 26551481 TI - YouTube as a patient-information source for root canal treatment. AB - AIM: To assess the content and completeness of YoutubeTM as an information source for patients undergoing root canal treatment procedures. METHODOLOGY: YouTubeTM (https://www.youtube.com/) was searched for information using three relevant treatment search terms ('endodontics', 'root canal' and 'root canal treatment'). After exclusions (language, no audio, >15 min, duplicates), 20 videos per search term were selected. General video assessment included duration, ownership, views, age, likes/dislikes, target audience and video/audio quality, whilst content was analysed under six categories ('aetiology', 'anatomy', 'symptoms', 'procedure', 'postoperative course' and 'prognosis'). Content was scored for completeness level and statistically analysed using anova and post hoc Tukey's test (P < 0.05). RESULTS: To obtain 60 acceptable videos, 124 were assessed. Depending on the search term employed, the video content and ownership differed markedly. There was wide variation in both the number of video views and 'likes/dislikes'. The average video age was 788 days. In total, 46% of videos were 'posted' by a dentist/specialist source; however, this was search term specific rising to 70% of uploads for the search 'endodontic', whilst laypersons contributed 18% of uploads for the search 'root canal treatment'. Every video lacked content in the designated six categories, although 'procedure' details were covered more frequently and in better detail than other categories. Videos posted by dental professional (P = 0.046) and commercial sources (P = 0.009) were significantly more complete than videos posted by laypeople. CONCLUSIONS: YouTubeTM videos for endodontic search terms varied significantly by source and content and were generally incomplete. The danger of patient reliance on YouTubeTM is highlighted, as is the need for endodontic professionals to play an active role in directing patients towards alternative high-quality information sources. PMID- 26551483 TI - Safety and effectiveness of insulin detemir in combination with oral antidiabetic agents in an outpatient specialist setting: results of the Italian SOLVETM observational study. AB - AIM: The addition of basal insulin to oral antidiabetics (OADs) is described by a large number of guidelines and commonly used in clinical practice as a way to start insulin therapy in patients with type 2 diabetes mellitus in order to maximize compliance and minimise the impact of side effects (mainly hypoglycemia and body weight increase). METHODS: SOLVETM was a 24-week international observational study conducted in 10 countries (including Italy) for the evaluation of the safety and effectiveness of once-daily insulin detemir as add on therapy in patients with type 2 diabetes mellitus (T2DM) already treated with one or more OADs. The Italian arm of the SolveTM Study aimed to evaluate the safety and the effectiveness of once-daily insulin detemir in combination with OAD agents for the treatment of patients with T2DM in the Italian outpatient specialist setting. The primary endpoint was to assess the incidence of serious adverse drug reactions (SADRs) including in the specific major hypoglycemic events during 24 weeks of once-daily insulin detemir treatment. RESULTS: A total of 4625 patients were enrolled in the study by 223 Italian centres for diabetes care. At baseline the mean (+/-SD) demographic characteristics of the patients were: age 66.5 (+/-10.0) years, duration of diabetes 13.25 (+/-8.14) years, weight 78.95 (+/-15.86) kg and BMI 29.5 (+/-5.0) kg/m2. At the end of the study, 3 SADRs (of which 2 were major hypoglycemia) were reported in 2 patients (<0.1%). The percentage of patients with at least 1 minor hypoglycemic event during the 4 weeks preceding insulin initiation was 3.6%. Following insulin initiation, 5.7% (as recorded at baseline visit) had at least 1 minor hypoglycemic event, which decreased slightly by the end of the study compared to baseline (4.8%). In addition, before insulin initiation the mean (+/-SD) glycemic control values were: fasting plasma glucose (FPG) 11.43 (+/-3.2) mmol/L and HbA1c 9.16% (+/ 1.46). At the end of the study, HbA1c was reduced by 1.35% (+/-1.57) (P<0.001), FPG was reduced by 3.34 mmol/L (P<0.001) and the percentage of patients with HbA1c<7% was 21.9%. A mean reduction of 0.52 kg of body weight (P<0.001) was observed compared to before insulin initiation; the body weight reduction was more pronounced in patients with higher BMI before insulin initiation (-1.0 kg for 3095% and provide the real possibility of eliminating hepatitis C virus. PMID- 26551492 TI - The use of ambulatory blood pressure measurement. AB - Measurement of ambulatory blood pressure is recommended by the National Institute for Health and Care Excellence guidelines to confirm the diagnosis of hypertension in the UK. This article describes the use of ambulatory devices, and discusses the benefits and disadvantages of their use in clinical practice. PMID- 26551493 TI - Deciding on a combination of anticoagulant and antiplatelet drugs. AB - Patients being treated for atrial fibrillation may develop cardiovascular disease before or after the onset of their heart rhythm problem, and may require a combination of antiplatelet and anticoagulant drugs. This article describes the evidence for the combinations used to treat acute coronary syndrome in patients with atrial fibrillation. PMID- 26551494 TI - Promoting equality by assessing discrimination in clinical practice. AB - How well do you understand your impact on the opportunities of others, and their impact on your opportunities? Do you reflect on the equality of your values and whether your behaviour could be improved? This article gives an overview of these issues for hospital doctors. PMID- 26551495 TI - Diagnosing and treating hepatic encephalopathy. AB - Hepatic encephalopathy is a complex condition. This article considers the efficacy of the methods used in its diagnosis and management and discusses the impact of minimal hepatic encephalopathy on patients and the ethics of its treatment. PMID- 26551496 TI - Readmission rates and financial penalties after ear, nose and throat surgery: how can we improve? AB - INTRODUCTION: Since April 2011, all patient readmissions within 30 days have resulted in a financial penalty to the hospital trust, and therefore the responsible department. These costs may be substantial and potentially preventable. METHODS: A service evaluation of readmissions within 30 days of discharge, over a 12-month period (January-December 2012), was performed in the ear, nose and throat department of a district general hospital, and findings were used as a basis to suggest areas for potential quality improvement. AIMS: To determine the number of readmissions, causes of readmission and resulting costs, and to explore how these readmissions may be prevented. RESULTS: The departmental 30-day readmission rate over the study period was 3.12% (81/2606). The commonest causes of readmission (33.3%) were complications following tonsillectomy (27/81) such as pain, infection or bleeding. Over a third of these patients (30/81) were readmitted for less than 24 hours, with the average length of stay being less than 2.5 days. Financial implications: In 2011 the trust had 7526 emergency readmissions which were eligible for penalty within the 30-day time frame. This resulted in a loss of income of more than L60 000 to the ear, nose and throat department. CONCLUSIONS: Optimizing postoperative care and improving patient understanding of common complications may reduce readmission rates, thus limiting the financial burden on the trust. These areas could serve as a basis for future quality improvement projects. PMID- 26551498 TI - John Coakley Lettsom: physician and philanthropist. PMID- 26551497 TI - Performing lumbar punctures for suspected CNS infections: experience and practice of trainee doctors. AB - Lumbar punctures are essential in the management of suspected CNS infections. However, despite clear guidelines their use can be haphazard. This survey investigated the training, knowledge and experience of UK doctors in training in relation to lumbar punctures. PMID- 26551499 TI - Renal tubular acidosis type 1 causing hypokalaemic periodic paralysis. PMID- 26551500 TI - Stomal metastasis of colorectal cancer. PMID- 26551501 TI - Timing of surgery following recent ischaemic stroke. PMID- 26551502 TI - Relapsing polychondritis presenting as recurrent otitis externa. PMID- 26551503 TI - Tackling NHS litigation costs needs better professional oversight. PMID- 26551504 TI - Erratum. PMID- 26551506 TI - Is there a role for codeine in paediatric anaesthetic practice? PMID- 26551507 TI - Cutaneous lupus erythematosus. PMID- 26551508 TI - Cutaneous drug rashes. PMID- 26551509 TI - The Koebner phenomenon. PMID- 26551510 TI - Pyoderma gangrenosum. PMID- 26551512 TI - Looking Back at the 30th Nagoya International Cancer Treatment Symposium. PMID- 26551513 TI - Alkaloids with Different Carbon Units from Myrioneuron faberi. AB - Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7. PMID- 26551514 TI - Reply to "Repurposing of metformin in liver injury: The JNK conundrum". PMID- 26551515 TI - Capitalising on improved rates of diagnosis of early hepatocellular carcinoma. PMID- 26551516 TI - Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems. AB - BACKGROUND & AIMS: Multiple staging systems have been proposed for hepatocellular carcinoma (HCC). However there is no consensus regarding which system provides the best prognostic accuracy. We aimed to investigate the performance of 11 currently used HCC staging systems. METHODS: Between 2002 and 2013, a large prospective dataset of 3182 HCC patients were enrolled. The baseline characteristics and staging information were collected. Independent predictors of survival were identified. Homogeneity and corrected Akaike information criterion (AICc) were compared between each system. RESULTS: The median follow-up duration was 17months. Independent predictors of adverse outcome were serum albumin <3.5g/dl, bilirubin ?1mg/dl, creatinine ?1mg/dl, alpha-fetoprotein ?20ng/ml, alkaline phosphatase ?200IU/L, presence of ascites, multiple tumor nodules, maximal tumor size >5cm, presence of vascular invasion, presence of extrahepatic metastasis, and poor performance status (all p<0.001). Significant differences in survival were found across all stages of the 11 systems except between Hong Kong Liver Cancer stage IV and V, Japan Integrated Staging score 4 and 5, and Tokyo score 5 through 8. The Cancer of the Liver Italian Program (CLIP) score was associated with the highest homogeneity and lowest AICc value in the entire cohort. In subgroup analysis, the CLIP score was also superior in patients with hepatitis B- or hepatitis C-related HCC and in patients receiving curative or non curative treatments. CONCLUSIONS: The CLIP staging system is stable and consistently the best prognostic model in all patients and in patients with different viral etiology and treatment strategy. PMID- 26551517 TI - Adverse effects of platelets on post-hepatectomy outcomes in patients with hepatocellular carcinoma. PMID- 26551511 TI - Small Molecule Active Site Directed Tools for Studying Human Caspases. AB - Caspases are proteases of clan CD and were described for the first time more than two decades ago. They play critical roles in the control of regulated cell death pathways including apoptosis and inflammation. Due to their involvement in the development of various diseases like cancer, neurodegenerative diseases, or autoimmune disorders, caspases have been intensively investigated as potential drug targets, both in academic and industrial laboratories. This review presents a thorough, deep, and systematic assessment of all technologies developed over the years for the investigation of caspase activity and specificity using substrates and inhibitors, as well as activity based probes, which in recent years have attracted considerable interest due to their usefulness in the investigation of biological functions of this family of enzymes. PMID- 26551518 TI - Molecular Dynamics of Membrane-Spanning DNA Channels: Conductance Mechanism, Electro-Osmotic Transport, and Mechanical Gating. AB - DNA self-assembly has emerged as a new paradigm for design of biomimetic membrane channels. Several experimental groups have already demonstrated assembly and insertion of DNA channels into lipid bilayer membranes; however, the structure of the channels and their conductance mechanism have remained undetermined. Here, we report the results of molecular dynamics simulations that characterized the biophysical properties of the DNA membrane channels with atomic precision. We show that, while overall remaining stable, the local structure of the channels undergoes considerable fluctuations, departing from the idealized design. The transmembrane ionic current flows both through the central pore of the channel as well as along the DNA walls and through the gaps in the DNA structure. Surprisingly, we find that the conductance of DNA channels depend on the membrane tension, making them potentially suitable for force-sensing applications. Finally, we show that electro-osmosis governs the transport of druglike molecules through the DNA channels. PMID- 26551519 TI - The extent of default visual perspective taking in complex layouts. AB - Emerging research suggests that visual perspective taking might be based in part on a default, early developing cognitive process. This hypothesis receives support from experiments demonstrating that adults experience interference from task-irrelevant perspectives of depicted agents even when participants are making judgments about their own perspective. However, a number of recent articles conclude that this self-judgment interference effect may be because of simple directional cues alone, and might, therefore, not reflect processes specific to visual perspective taking. In 3 studies, we demonstrate that self-judgment interference is constrained by agents' apparent line-of-sight access to subspaces in realistic rendered scenes. Participants displayed processing costs when their perspective conflicted with that of an avatar, who faced in the direction of all possible targets but could not see some of the targets because of occlusion. This interference effect occurred using 2 different configurations of occluders, and disappeared when windows were added to the occluders, allowing avatars line of sight access to all of the targets visible to the participant. These results demonstrate that default perspective taking is not attributable to directional cues alone but instead reflects a relatively sophisticated calculation of an agent's line of sight. (PsycINFO Database Record PMID- 26551521 TI - Cystic fibrosis program directors' attitudes toward sexual and reproductive health in young women with CF. AB - INTRODUCTION: Advancements in therapy have led to dramatic increases in the life expectancy of patients with cystic fibrosis (CF). As survival improves, young women with CF will have expectations for their sexual and reproductive health (SRH) futures similar to their counterparts without CF. As they face unique CF specific SRH concerns, they may rely on CF care providers for disease-specific SRH care provision. The purpose of this study was to investigate the attitudes of CF providers toward female SRH and perceived barriers in the current CF care model. MATERIALS AND METHODS: U.S. CF program directors (n = 16) participated in qualitative interviews investigating attitudes and barriers to female CF SRH care. Interviews were audio-recorded, transcribed, and coded using a thematic analysis approach. RESULTS: Participants (nine pediatric, five adult, and two combined) all agreed CF providers have a fundamental role in CF female SRH care. Most respondents named lack of time and patient and provider discomfort as significant barriers to effective SRH communication. Other reported barriers included: lack of training in SRH, family members in the room, low priority of SRH in setting of other CF issues, and lack of adequate rapport with patients. DISCUSSION: This is the first study to assess the attitudes and experiences of CF care providers toward SRH discussion and care among female CF patients. Despite their perceived fundamental role in CF female SRH care, CF providers face significant barriers. Investment in provider training is needed to better address the complex SRH needs of young female patients. PMID- 26551520 TI - Subacute cutaneous lupus erythematosus induced by capecitabine: 5-FU was innocent. PMID- 26551522 TI - Structural Insights into Ternary Complex Formation of Human CARM1 with Various Substrates. AB - Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine N-methyltransferase (PRMT) enzyme that has been implicated in a variety of cancers. CARM1 is known to methylate histone H3 and nonhistone substrates. To date, several crystal structures of CARM1 have been solved, including structures with small molecule inhibitors, but no ternary structures with nucleoside and peptide substrates have been reported. Here, the crystal structures of human CARM1 with the S-adenosylmethione (SAM) mimic sinefungin and three different peptide sequences from histone H3 and PABP1 are presented, with both nonmethylated and singly methylated arginine residues exemplified. This is the first example of multiple substrate sequences solved in a single PRMT enzyme and demonstrates how the CARM1 binding site is capable of accommodating a variety of peptide sequences while maintaining a core binding mode for the unmethylated and monomethylated substrates. Comparison of these with other PRMT enzyme-peptide structures shows hydrogen bonding patterns that may be thematic of these binding sites. PMID- 26551523 TI - CD/MCD/VTVH-MCD Studies of Escherichia coli Bacterioferritin Support a Binuclear Iron Cofactor Site. AB - Ferritins and bacterioferritins (Bfrs) utilize a binuclear non-heme iron binding site to catalyze oxidation of Fe(II), leading to formation of an iron mineral core within a protein shell. Unlike ferritins, in which the diiron site binds Fe(II) as a substrate, which then autoxidizes and migrates to the mineral core, the diiron site in Bfr has a 2-His/4-carboxylate ligand set that is commonly found in diiron cofactor enzymes. Bfrs could, therefore, utilize the diiron site as a cofactor rather than for substrate iron binding. In this study, we applied circular dichroism (CD), magnetic CD (MCD), and variable-temperature, variable field MCD (VTVH-MCD) spectroscopies to define the geometric and electronic structures of the biferrous active site in Escherichia coli Bfr. For these studies, we used an engineered M52L variant, which is known to eliminate binding of a heme cofactor but to have very minor effects on either iron oxidation or mineral core formation. We also examined an H46A/D50A/M52L Bfr variant, which additionally disrupts a previously observed mononuclear non-heme iron binding site inside the protein shell. The spectral analyses define a binuclear and an additional mononuclear ferrous site. The biferrous site shows two different five coordinate centers. After O2 oxidation and re-reduction, only the mononuclear ferrous signal is eliminated. The retention of the biferrous but not the mononuclear ferrous site upon O2 cycling supports a mechanism in which the binuclear site acts as a cofactor for the O2 reaction, while the mononuclear site binds the substrate Fe(II) that, after its oxidation to Fe(III), migrates to the mineral core. PMID- 26551524 TI - Surgical Intervention in Terminal Illness--Doing Everything: A Teachable Moment. PMID- 26551525 TI - Comparison of vaginal microbial community structure in healthy and endometritis dairy cows by PCR-DGGE and real-time PCR. AB - The normal vaginal microflora provides protection against infections of the reproductive tract. Previous studies have focused on the isolation and screening of probiotic strains from the vagina of cows; however, the vaginal microflora of postpartum cows is poorly characterized. The present study was conducted to evaluate and characterize the vaginal microflora of healthy postpartum cows in relation to postpartum cows with endometritis by using PCR followed by denaturing gradient gel electrophoresis (PCR-DGGE) and Real-time PCR. The study population comprised 5 healthy cows and 5 cows with endometritis. The results indicated that the vaginal bacterial microflora of healthy postpartum cows was dominated by Lactobacillus sakei subsp. and Weissella koreensis, while there were no dominant bacterial species in the vaginal microflora of postpartum cows with endometritis. Common microorganisms such as Bacteroides spp., Fusobacterium spp., Enterococcus spp., Prevotella spp., Clostridium perfringens strains, and Escherichia coli were detected in both groups of cows by Real-time PCR. The bacterial diversity in the vagina of cows with endometritis was significantly higher than that in healthy cows. The results indicated that the vaginal microflora of cows with endometritis was more diverse and lacked dominant bacterial species as compared to that of the healthy cows, suggesting that disruption of the normal vaginal microflora may contribute to the onset of endometritis. This microbial community analysis provided information that might be used to develop probiotics to treat endometritis in cows; however, further investigation is needed. PMID- 26551526 TI - SH2 Ligand-Like Effects of Second Cytosolic Domain of Na/K-ATPase alpha1 Subunit on Src Kinase. AB - Our previous studies have suggested that the alpha1 Na/K-ATPase interacts with Src to form a receptor complex. In vitro binding assays indicate an interaction between second cytosolic domain (CD2) of Na/K-ATPase alpha1 subunit and Src SH2 domain. Since SH2 domain targets Src to specific signaling complexes, we expressed CD2 as a cytosolic protein and studied whether it could act as a Src SH2 ligand in LLC-PK1 cells. Co-immunoprecipitation analyses indicated a direct binding of CD2 to Src, consistent with the in vitro binding data. Functionally, CD2 expression increased basal Src activity, suggesting a Src SH2 ligand-like property of CD2. Consistently, we found that CD2 expression attenuated several signaling pathways where Src plays an important role. For instance, although it increased surface expression of Na/K-ATPase, it decreased ouabain-induced activation of Src and ERK by blocking the formation of Na/K-ATPase/Src complex. Moreover, it also attenuated cell attachment-induced activation of Src/FAK. Consequently, CD2 delayed cell spreading, and inhibited cell proliferation. Furthermore, these effects appear to be Src-specific because CD2 expression had no effect on EGF-induced activation of EGF receptor and ERK. Hence, the new findings indicate the importance of Na/K-ATPase/Src interaction in ouabain induced signal transduction, and support the proposition that the CD2 peptide may be utilized as a Src SH2 ligand capable of blocking Src-dependent signaling pathways via a different mechanism from a general Src kinase inhibitor. PMID- 26551527 TI - Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer. AB - OBJECTIVES: Previous non-simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment. METHODS: We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body 18F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV. RESULTS: 92 lesions were detected. We found a significant inverse correlation between SUVmax and ADCmin (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = 0.362, p = 0.05) and between SUVmean and ADCmin (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUVmax and ADCmin (r = -0.747, p = 0.002) and SUVmean and ADCmin (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05). CONCLUSIONS: Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions. PMID- 26551528 TI - Olive Oil, Sunflower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study). AB - Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. One hundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79 100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin. PMID- 26551529 TI - An Autopsy Case of Dementia with Lewy Bodies with Vocal Cord Abductor Paralysis. PMID- 26551530 TI - Midlife Eriksonian psychosocial development: Setting the stage for late-life cognitive and emotional health. AB - Erikson's (1950) model of adult psychosocial development outlines the significance of successful involvement within one's relationships, work, and community for healthy aging. He theorized that the consequences of not meeting developmental challenges included stagnation and emotional despair. Drawing on this model, the present study uses prospective longitudinal data to examine how the quality of assessed Eriksonian psychosocial development in midlife relates to late-life cognitive and emotional functioning. In particular we were interested to see whether late-life depression mediated the relationship between Eriksonian development and specific domains of cognitive functioning (i.e., executive functioning and memory). Participants were 159 men from the over-75 year longitudinal Study of Adult Development. The sample was comprised of men from both higher and lower socioeconomic strata. Eriksonian psychosocial development was coded from men's narrative responses to interviews between the ages of 30-47 (Vaillant & Milofsky, 1980). In late life (ages 75-85) men completed a performance-based neuropsychological assessment measuring global cognitive status, executive functioning, and memory. In addition depressive symptomatology was assessed using the Geriatric Depression Scale. Our results indicated that higher midlife Eriksonian psychosocial development was associated with stronger global cognitive functioning and executive functioning, and lower levels of depression 3 to 4 decades later. There was no significant association between Eriksonian development and late-life memory. Late-life depression mediated the relationship between Eriksonian development and both global cognition and executive functioning. All of these results controlled for highest level of education and adolescent intelligence. Findings have important implications for understanding the lasting benefits of psychosocial engagement in mid-adulthood for late-life cognitive and emotional health. In addition, it may be that less successful psychosocial development increases levels of depression making individuals more vulnerable to specific areas of cognitive decline. PMID- 26551531 TI - Summaries for Patients. Normal-Weight Central Obesity and Mortality. PMID- 26551532 TI - Does marital status matter in an HIV hyperendemic country? Findings from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. AB - South Africa has experienced declining marriage rates and the increasing practice of cohabitation without marriage. This study aims to improve the understanding of the relationship between marital status and HIV in South Africa, an HIV hyperendemic country, through an analysis of findings from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. The nationally representative population-based cross-sectional survey collected data on HIV and socio-demographic and behavioural determinants in South Africa. This analysis considered respondents aged 16 years and older who consented to participate in the survey and provided dried blood spot specimens for HIV testing (N = 17,356). After controlling for age, race, having multiple sexual partners, condom use at last sex, urban/rural dwelling and level of household income, those who were married living with their spouse had significantly reduced odds of being HIV positive compared to all other marital spouses groups. HIV incidence was 0.27% among respondents who were married living with their spouses; the highest HIV incidence was found in the cohabiting group (2.91%). Later marriage (after age 24) was associated with increased odds of HIV prevalence. Our analysis suggests an association between marital status and HIV prevalence and incidence in contemporary South Africa, where odds of being HIV-positive were found to be lower among married individuals who lived with their spouses compared to all other marital status groups. HIV prevention messages therefore need to be targeted to unmarried populations, especially cohabitating populations. As low socio-economic status, low social cohesion and the resulting destabilization of sexual relationships may explain the increased risk of HIV among unmarried populations, it is necessary to address structural issues including poverty that create an environment unfavourable to stable sexual relationships. PMID- 26551533 TI - A HPLC-MS/MS method for the quantitation of free, conjugated, and total HDND-7, a novel hesperetin derivative, in rat plasma and tissues: Application to the pharmacokinetic and tissue distribution study. AB - A sensitive and reliable HPLC-MS/MS method was developed and validated for the determination of free (unconjugated), glucuronidated, sulfated, and total (free and conjugated) HDND-7 in rat plasma and tissues. Plasma and tissues samples were treated prior to and after the enzyme hydrolysis. Chromatographic separation was achieved on a Phenomenex Luna C18 column (150 * 4.6mm, 3 MUm), using isocratic mobile phase consisting of 0.1% formic acid-acetonitrile (50:50, v/v) at a flow rate of 300 MUl/min. The detection was performed on a triple quadruple tandem mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 5.0 min. The detection was operated by multiple reaction monitoring (MRM) of the transitions of m/z 429.3 -> 223.9 for HDND-7 and 272.9 -> 152.9 for naringenin (IS), respectively. This method was validated in terms of specificity, linearity, precision, accuracy, and stability. The calibration curves for plasma and tissues were linear over a wide concentration range of 0.02-40 MUg/ml with a lower limit of quantification (LLOQ) of 0.02 MUg/ml. Mean extraction recoveries in plasma and tissues ranged from 87.4 to 97.1% and from 54.2 to 70.5%, respectively. The intra- and inter-day precision values were below 15% and the accuracy was within +/- 15%. The samples were stable under all the tested conditions. This method has been successfully applied to the pharmacokinetic study following oral doses of 25, 50 and 100mg/kg and intravenous dose of 25mg/kg, and tissue distribution study following oral dose of 50mg/kg. PMID- 26551534 TI - Determination of endogenous concentration of gamma-hydroxybutyric acid (GHB) in hair through an ad hoc GC-MS analysis: A study on a wide population and influence of gender and age. AB - gamma-Hydroxybutyric acid (GHB) spread for recreational purposes or as "rape drug" represents a hard issue for forensic toxicologists due to its endogenous nature. It is clear that an actual and reliable discrimination between basal and exogenous levels is mandatory to achieve a correct evaluation of conscious/unconscious administration. This research aimed to study the GHB baseline in hair samples, collected from 150 volunteers, non-consumers of any drugs of abuse, in order to evaluate if a generic cut-off value could be accepted, also focusing on potential influences of gender and age. The analysis consisted of an overnight incubation with NaOH at 56 degrees C, liquid-liquid extraction with ethylacetate and trimethylsylil derivatization. Detection was carried out through gas chromatography-mass spectrometry in single ion monitoring (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in "blank" hair was estimated by the standard addition method. Concentration range was 0.279-2.839 ng/mg. In males, the average GHB levels were higher than in females (0.829 vs 0.596 ng/mg, respectively), especially in the first age category (<30 years, 1.008 vs 0.606 ng/mg, respectively). Age influences on GHB levels seemed to be different among the two sexes: in male population concentrations were higher <30 (1.008 ng/mg) and similar in the other age ranges (0.762 ng/mg, 30-50; 0.763 ng/mg, >50); in female, quite similar levels were registered throughout all the age categories (0.606 ng/mg, <30; 0.536 ng/mg, 30-50; 0.691 ng/mg, >50). Further study should be performed on GHB physiology in order to better understand these differences among ages and genders. Moreover, we demonstrated that for hair analysis a cut-off reference value is not strictly mandatory, underlining the great interpretative valence of segmental analysis. PMID- 26551535 TI - Screening and identification of three typical phenylethanoid glycosides metabolites from Cistanches Herba by human intestinal bacteria using UPLC/Q-TOF MS. AB - Acteoside, isoacteoside, and 2'-acetylacteoside are three representative phenylethanoid glycosides (PhGs), which are widely distributed in many plants and also known as the active components of Cistanches Herba. However, the extremely low oral bioavailability of acteoside in rats implies that these structural similar components may go through multiple sequential routes of hydrolysis in gastrointestinal tract before they are absorbed into blood. Therefore, the metabolites of these three components and other PhGs from gastrointestinal tract such as echinacoside, are supposed to be the bioactive elements. In this study, we established an approach combining ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) with MS(E) technology and MetaboLynxTM software for the rapid metabolic profiling of acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria. As a result, 11 metabolites of acteoside, 7 metabolites of isoacteoside, and 11 metabolites of 2'-acetylacteoside were identified respectively. 8 metabolic pathways including deglycosylation, de-rhamnose, de-hydroxytyrosol, de-caffeoyl, deacetylation, reduction, acetylation, and sulfate conjugation were proposed to involve in the generation of these metabolites. Furthermore, we found that the degraded metabolites hydroxytyrosol (HT) and 3-hydroxyphenylpropionic (3-HPP) were transformed from acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria and demonstrated similar bioactivities to their precursors. These findings are significant for our understanding of the metabolism of PhGs and the proposed metabolic pathways of bioactive components might be crucial for further pharmacokinetic evaluations of Cistanches Herba. PMID- 26551536 TI - A novel fluorescence aptasensor for 8-hydroxy-2'-deoxyguanosine based on the conformational switching of K(+)-stabilized G-quadruplex. AB - A sensitive, lable-free and low cost fluorescence aptasensor was developed for detecting 8-hydroxy-2'-deoxyguanosine (8-OHdG) by using 8-OHdG aptamer (Apt) as a recognition probe and N-methyl mesoporphyrin IX (NMM) as a reporter. The method is based on the conformational switching of a K(+)-stabilized G-quadruplex to a 8 OHdG-stabilized one. NMM can selectively bind to K(+)-stabilized G-quadruplex instead of 8-OHdG-stabilized one. The addition of 8-OHdG in the solution of Apt - K(+) ions leads to a sharp change in fluorescence intensity, which showed a good linear response toward 8-OHdG concentration ranging from 3.96 nM to 211 nM with a detection limit of 1.19 nM. The relative standard deviation and the recovery were 1.23-3.26% (n=11) and 94.8-106.7%, respectively. The proposed aptasensor consists of only an aptamer probe and a specific dye NMM, avoiding the complex and expensive labeling procedure. Thus it is much cheaper and more applicable. PMID- 26551537 TI - Identification, characterization and distribution of monoterpene indole alkaloids in Rauwolfia species by Orbitrap Velos Pro mass spectrometer. AB - Monoterpene indole alkaloids (MIAs) are medicinally important class of compounds abundant in the roots of Rauwolfia species (Apocynaceae). MIAs such as yohimbine (aphrodisiac agent) and reserpine (antihypertensive, tranquilizer) are the official drugs included in Model List of Essential Drugs of World Health Organization (WHO). Therefore, we have attempt to identify and characterize the MIAs in the crude extracts of six Rauwolfia species using ultrahigh-performance liquid chromatography coupled with Orbitrap Velos Pro hybrid mass spectrometer. The identity of the MIAs were construed using the high resolution tandem mass spectrometry (HRMS/MS) spectra of standard compounds 'yohimbine' and 'reserpine' in higher energy collisional dissociation (HCD) and collision-induced dissociation (CID) modes. The diagnostic fragment ions found in HCD mode was highly affected by variation of normalized collision energy (NCE) and gave few product ions ('C-F') while CID produced intense and more diagnostic product ions ('A-F'). Consequently, CID-MS/MS mode provided significantly more structural information about basic skeleton and therefore the recommended mode for analysis of MIAs. Furthermore, six diagnostic fragmentation pathways were established by multi-stage mass analysis (MS(n) (n=5)) analysis which gave information regarding the substitution. Fragment ions 'A-F' revealed the number and position of substituents on indole and terpene moieties. The proposed diagnostic fragmentation pathways have been successfully applied for identification and characterization of MIAs in crude root extracts of six Rauwolfia species. Ten bioactive reserpine class of MIAs were tentatively identified and characterized on the basis of chromatographic and mass spectrometric features as well as HRMS/MS an MS(n) (n=4) analysis. PMID- 26551539 TI - Self-Healing, Fully Functional, and Multiparametric Flexible Sensing Platform. AB - A non-biological and flexible self-healing platform has tailored sensitivity toward one or a combination of pressure, strain, gas analytes, and temperature. For demonstration, a complete self-healing device is described in the form of a bendable and stretchable chemiresistor, where every part is self-healing. PMID- 26551538 TI - Evaluation of an oral uracil loading test to identify DPD-deficient patients using a limited sampling strategy. AB - AIM: Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe toxicity following 5-fluorouracil (5FU) or capecitabine (CAP) treatment. Uracil (U) can be used as a probe to determine systemic DPD activity. The present study was performed to assess the sensitivity and specificity of a U loading dose for detecting DPD deficiency. METHODS: Cancer patients with Common Toxicity Score (CTC) grade III or IV toxicity after the first or second cycle of 5-FU or CAP treatment were asked to participate. Based on DPD activity in PBMCs, patients were divided into two groups: DPD activity in peripheral blood mononuclear cells (PBMCs) <5 nmol mg(-1) *h(-1) (deficient group) and >= 5 nmol mg(-1) *h(-1) . U 500 mg m(-2) was administered orally and plasma concentrations of U and dihydrouracil (DHU) were determined. In the deficient group, polymerase chain reaction amplification of all 23 coding exons and flanking intronic regions of DPYD was performed. A U pharmacokinetic model was developed and used to determine the maximum enzymatic conversion capacity (Vmax ) of the DPD enzyme for each patient. The sensitivity and specificity of Vmax, U concentration and the U/DHU concentration ratio were determined. RESULTS: A total of 47 patients were included (19 DPD deficient, 28 DPD normal). Of the pharmacokinetic parameters investigated, a sensitivity and specificity of 80% and 98%, respectively, was obtained for the U/DHU ratio at t = 120 min. CONCLUSIONS: The high sensitivity of the U/DHU ratio at t = 120 min for detecting DPD deficiency, as defined by DPD activity in PBMCs, showed that the oral U loading dose can effectively identify patients with reduced DPD activity. PMID- 26551540 TI - CLINICAL DECISIONS. Blood-Pressure Control. PMID- 26551541 TI - Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice. AB - Climbing fiber inputs to Purkinje cells are thought to be involved in generating the instructive signals that drive cerebellar learning. To investigate how these instructive signals are encoded, we recorded the activity of individual climbing fibers during cerebellum-dependent eyeblink conditioning in mice. We found that climbing fibers signaled both the unexpected delivery and the unexpected omission of the periocular airpuff that served as the instructive signal for eyeblink conditioning. In addition, we observed that climbing fibers activated by periocular airpuffs also responded to stimuli from other sensory modalities if those stimuli were novel or if they predicted that the periocular airpuff was about to be presented. This pattern of climbing fiber activity is markedly similar to the responses of dopamine neurons during reinforcement learning, which have been shown to encode a particular type of instructive signal known as a temporal difference prediction error. PMID- 26551542 TI - G9a is essential for epigenetic silencing of K(+) channel genes in acute-to chronic pain transition. AB - Neuropathic pain is a debilitating clinical problem and difficult to treat. Nerve injury causes a long-lasting reduction in K(+) channel expression in the dorsal root ganglion (DRG), but little is known about the epigenetic mechanisms involved. We found that nerve injury increased dimethylation of Lys9 on histone H3 (H3K9me2) at Kcna4, Kcnd2, Kcnq2 and Kcnma1 promoters but did not affect levels of DNA methylation on these genes in DRGs. Nerve injury increased activity of euchromatic histone-lysine N-methyltransferase-2 (G9a), histone deacetylases and enhancer of zeste homolog-2 (EZH2), but only G9a inhibition consistently restored K(+) channel expression. Selective knockout of the gene encoding G9a in DRG neurons completely blocked K(+) channel silencing and chronic pain development after nerve injury. Remarkably, RNA sequencing analysis revealed that G9a inhibition not only reactivated 40 of 42 silenced genes associated with K(+) channels but also normalized 638 genes down- or upregulated by nerve injury. Thus G9a has a dominant function in transcriptional repression of K(+) channels and in acute-to-chronic pain transition after nerve injury. PMID- 26551543 TI - Optogenetic acidification of synaptic vesicles and lysosomes. AB - Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes. PMID- 26551544 TI - Piezo2 is the principal mechanotransduction channel for proprioception. AB - Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors. PMID- 26551546 TI - Decreased amyloid-beta and increased neuronal hyperactivity by immunotherapy in Alzheimer's models. AB - Among the most promising approaches for treating Alzheimer's disease is immunotherapy with amyloid-beta (Abeta)-targeting antibodies. Using in vivo two photon imaging in mouse models, we found that two different antibodies to Abeta used for treatment were ineffective at repairing neuronal dysfunction and caused an increase in cortical hyperactivity. This unexpected finding provides a possible cellular explanation for the lack of cognitive improvement by immunotherapy in human studies. PMID- 26551547 TI - Impact of topical application of sulfur mustard on mice skin and distant organs DNA repair enzyme signature. AB - Sulfur mustard (SM) is a chemical warfare agent that, upon topical application, damages skin and reaches internal organs through diffusion in blood. Two major toxic consequences of SM exposure are inflammation, associated with oxidative stress, and the formation of alkylated DNA bases. In the present study, we investigated the impact of exposure to SM on DNA repair, using two different functional DNA repair assays which provide information on several Base Excision Repair (BER) and Excision/Synthesis Repair (ESR) activities. BER activities were reduced in all organs as early as 4h after exposure, with the exception of the defense systems against 8-oxo-guanine and hypoxanthine which were stimulated. Interestingly, the resulting BER intermediates could activate inflammation signals, aggravating the inflammation triggered by SM exposure and leading to increased oxidative stress. ESR activities were found to be mostly inhibited in skin, brain and kidneys. In contrast, in the lung there was a general increase in ESR activities. In summary, exposure to SM leads to a significant decrease in DNA repair in most organs, concomitant with the formation of DNA damage. These synergistic genotoxic effects are likely to participate in the high toxicity of this alkylating agent. Lungs, possibly better equipped with repair enzymes to handle exogenous exposure, are the exception. PMID- 26551545 TI - Parcellating cortical functional networks in individuals. AB - The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and behavior. Here we developed a cortical parcellation approach to accurately map functional organization at the individual level using resting-state functional magnetic resonance imaging (fMRI). A population-based functional atlas and a map of inter-individual variability were employed to guide the iterative search for functional networks in individual subjects. Functional networks mapped by this approach were highly reproducible within subjects and effectively captured the variability across subjects, including individual differences in brain lateralization. The algorithm performed well across different subject populations and data types, including task fMRI data. The approach was then validated by invasive cortical stimulation mapping in surgical patients, suggesting potential for use in clinical applications. PMID- 26551548 TI - Zebra mussel as a new tool to show evidence of freshwater contamination by waterborne Toxoplasma gondii. AB - AIMS: The objective of this study was to evaluate if freshwater bivalves can be used to detect the presence of Toxoplasma gondii in water bodies. METHODS AND RESULTS: Zebra mussels (Dreissena polymorpha) were caged for 1 month upstream and downstream of the discharge points of wastewater treatment plants (WWTPs). Physiological status was assessed to assure good health of bivalves during transplantation. The presence of T. gondii was investigated in mussel tissues by qPCR. In autumn, T. gondii was detected in mussels caged downstream of the discharge points of two WWTPs. In spring, it was detected upstream of one WWTP. CONCLUSIONS: For the first time, T. gondii DNA has been shown in a continental mollusc in environmental conditions. This highlights the interest of an active approach that could be applied independently of the presence or accessibility of autochthonous populations, and underlines the presence of T. gondii in natural waters under pressure of WWTP discharge at a certain time of the year. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that transplanted zebra mussels could be used as biosamplers to reveal contamination of freshwater systems by T. gondii. PMID- 26551549 TI - Genomic Characterization of Dehalococcoides mccartyi Strain JNA That Reductively Dechlorinates Tetrachloroethene and Polychlorinated Biphenyls. AB - Dehalococcoides mccartyi strain JNA detoxifies highly chlorinated polychlorinated biphenyl (PCB) mixtures via 85 distinct dechlorination reactions, suggesting that it has great potential for PCB bioremediation. However, its genomic and functional gene information remain unknown due to extremely slow growth of strain JNA with PCBs. In this study, we used tetracholorethene (PCE) as an alternative electron acceptor to grow sufficient biomass of strain JNA for subsequent genome sequencing and functional gene identification. Analysis of the assembled draft genome (1 462 509 bp) revealed the presence of 29 putative reductive dehalogenase (RDase) genes. Among them, JNA_RD8 and JNA_RD11 genes were highly transcribed in both PCE- and PCB-fed cultures. Furthermore, in vitro assays with crude cell lysate from PCE grown cells revealed dechlorination activity against both PCE and 2,2',3,4,4',5,5'-heptachlorobiphenyl. These data suggest that both JNA_RD8 and JNA_RD11 may be bifunctional PCE/PCB RDases. This study deepens the knowledge of organohalide respiration of PCBs and facilitates in situ PCB-bioremediation with strain JNA. PMID- 26551550 TI - Ramosetron Reduces Symptoms of Irritable Bowel Syndrome With Diarrhea and Improves Quality of Life in Women. AB - BACKGROUND & AIMS: Previous studies have indicated that serotonin-3-receptor antagonists might have a sex-specific effect in patients with irritable bowel syndrome with diarrhea (IBS-D). Alosetron has been approved for the treatment of only women, and ramosetron has been approved for the treatment for only men. We performed a randomized, placebo-controlled, phase 3 study to determine whether ramosetron reduces symptoms of IBS-D in women. METHODS: We performed a prospective study of 576 female outpatients with IBS-D (according to the Rome III criteria), from February 2013 through February 2014, at 70 academic Gastroenterology Departments in Japan. After a 1-week baseline period, subjects received either 2.5 MUg ramosetron (n = 292) or placebo (n = 284) once daily for 12 weeks. Primary end points were the monthly rates of response for relief from overall IBS symptoms and increased stool consistency at the last evaluation point. Quality of life (QOL) also was quantified. RESULTS: A significantly higher proportion of patients given ramosetron reported global improvement (50.7%; 95% confidence interval [CI], 44.8-56.6) than patients given placebo (32.0%; 95% CI, 26.7-37.8)--a difference of 18.6% (95% CI, 10.7-26.5; P < .001). The relative risk was 1.58 (95% CI, 1.29-1.94) and the number needed to treat was 6 (95% CI, 4 10). A significantly higher proportion of patients in the ramosetron group reported increased stool consistency (40.8%; 95% CI, 35.1%-46.6%) than in the placebo group (24.3%; 95% CI, 19.4%-29.7%)--a difference of 16.5% (95% CI, 8.9% 24.0%; P < .001). Patients receiving ramosetron had significant reductions in abdominal pain and discomfort (P = .001) and greater improvement in QOL (P = .002) compared with placebo. Ramosetron induced constipation in 11.0% of patients. CONCLUSIONS: In a randomized, placebo-controlled study of 576 women with IBS-D, 2.5 MUg ramosetron per day reduced symptoms and increased stool consistency and QOL. Clinicaltrials.gov no: NCT01870895. PMID- 26551551 TI - Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk. AB - There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared it with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, therefore camelid HEV, which is genotype 7, might infect human beings. Our finding links consumption of camel-derived food products to post transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents. PMID- 26551553 TI - Double esophageal perforation by ingested foreign body: Endoscopic and surgical approach. A case report. AB - INTRODUCTION: Esophageal perforation in adults is most frequently caused by ingested foreign bodies. They can migrate through the esophageal wall, damaging the nearby organs such as the aorta or the trachea, with fatal outcome. After the diagnosis, the viable treatments for extracting the foreign body and repairing the perforation are several. The appropriate treatment, may be endoscopic, surgical or combined, depending on the level of the perforation, on the co morbidities of the patient and on the available resources. PRESENTATION OF CASE: This paper describes a case of a 68 years old patient with a double EP caused by a meat-bone that perforated the thoracic esophageal wall, approaching the aorta on the left side and the azygos vein on the right side. DISCUSSION: Because of the double transfixion and the position near the aorta and the azygos, it was not possible to remove safely the bone during the endoscopy. The management required a combined endoscopic and surgical approach. This way it was possible to detect easily the location of the perforation, to remove safely the foreign body, to repair the perforation both from the outside and from the inside, and to place the nasogastric tube under direct vision. CONCLUSION: Even when the type of esophageal perforation requires surgical treatment, the simultaneous use of endoscopy proved to be an advantage in order to extract the foreign body safely, to perform a double repair of the perforation and to place the nasogastric tube under direct vision. PMID- 26551554 TI - A case of Menetrier's disease without Helicobacter pylori or hypoalbuminemia. AB - INTRODUCTION: Menetrier's disease is a rare premalignant hypertrophic gastropathy. It is characterized by huge gastric mucosal folds, peripheral edema due to protein loss and upper GIT symptoms such as epigastric pain, discomfort, nausea and vomiting. PRESENTATION OF CASE: Female patient 35 years old complaining of severe epigastric pain, dyspepsia, nausea and vomiting for 1 year. Upper GIT endoscopy and CT scan revealed thickening of gastric mucosa. Endoscopic biopsy was non-specific but showed moderate grade dysplasia and no Helicobacter pylori infection. All laboratory investigations were within normal including serum albumin. She underwent total gastrectomy with marked postoperative improvement of symptoms after recovery. Postoperative pathology revealed gastric fovular hyperplasia and glandular atrophy which are diagnostic for Menetrier's disease. DISCUSSION: the preoperative diagnosis of Menetrier's disease in this case was challenged by its unusual features. There were neither H. pylori nor hypoalbuminemia. Literature review showed similarcases which can raise the suspicion of the presence of an undescribed subtype of the disease. CONCLUSION: Menetrier's disease should be suspected in cases of upper GIT symptoms and hypertrophied gastric mucosa with or without H. pylori or hypoalbuminemia. The preoperative diagnosis could not be confirmed unless a whole mucosal thickness biopsy is performed. Surgical management is a good option when medical treatment fails to relieve the symptoms and erase the risk of malignancy. PMID- 26551555 TI - Sigmoid volvulus during pregnancy: A rare non-obstetric complication. Report of a case and review of the literature. AB - INTRODUCTION: Sigmoid volvulus is a rare cause of intestinal obstruction during pregnancy associated with high maternal and foetal mortality. Effective management represents a challenge due to delayed presentation, obstructive symptoms regarded as pregnancy-related and hesitation in using radiological evaluation. PRESENTATION OF CASE: We report a case of a lady, pregnant for 26 weeks and with a 5 day history of abdominal pain and constipation. She underwent concomitant caesarean section and laparotomy for intestinal obstruction. Intra operatively, the sigmoid colon was extensively dilated and gangrenous. The ischemic colon was resected and a Hartmann's procedure was performed. A preterm male child was delivered and admitted to neonatal intensive care. The post operative course was uneventful and the patient was discharged home on the 9th post-operative day. Six months later she underwent an uneventful reversal of the Hartmann's procedure. DISCUSSION: Sigmoid volvulus is the most common cause of bowel obstruction during pregnancy, accounting for up to 44% of reported cases. We have reviewed the available literature on this topic and present another case managed at our institution. CONCLUSION: Diagnosis of sigmoid volvulus in pregnancy is a challenge, but a delay in diagnosis increases the rates of feto maternal mortality. A high incidence of clinical suspicion and timely surgical intervention are the key to a favourable outcome. PMID- 26551556 TI - A delayed foreskin-sparing approach to the management of penile fractures in uncircumcised Jamaican men. AB - INTRODUCTION: The traditional surgical approach to penile fracture is to perform a circumferential subcoronal degloving incision emergently to repair the injury. This approach necessitates circumcision to avoid foreskin complications. We present four men who had a delayed foreskin-sparing approach and discuss its advantages. PRESENTATION OF CASE: Four of five uncircumcised patients who had suspected penile fractures secondary to coital injury, and without suspicion of concomitant urethral injury, had a delayed exploration, seven days after injury, utilizing an incision directly over the palpable haematoma, at the location of the tunical defect, thereby resulting in foreskin preservation. Two of 5 patients had repair under general anaesthesia, one under local anaesthesia and surgery was cancelled in another because upon reassessment at seven days he had normal erections and a normal penile examination. At follow up, all men had good functional and cosmetic outcomes. DISCUSSION: Uncircumcised patients with penile fractures, without suspicion of urethral injury, may undergo a delayed repair without prophylactic circumcision since there is minimal risk of foreskin complications. Delayed repair decreases the incidence of negative explorations by fostering a conservative approach in mimicking conditions such as superficial vein lacerations. It also enables the use of local anaesthesia in an elective ambulatory setting. CONCLUSION: Delayed repair of penile fractures results in foreskin preservation, facilitates elective ambulatory care under local anaesthesia and decreases the incidence of negative surgical explorations. PMID- 26551557 TI - Stability analysis and optimal control of an epidemic model with awareness programs by media. AB - The impact of awareness campaigns and behavioral responses on epidemic outbreaks has been reported at times. However, to what extent does the provision of awareness and behavioral changes affect the epidemic trajectory is unknown, but important from the public health standpoint. To address this question, we formulate a mathematical model to study the effect of awareness campaigns by media on the outbreak of an epidemic. The awareness campaigns are treated as an intervention for the emergent disease. These awareness campaigns divide the whole populations into two subpopulation; aware and unaware, by inducing behavioral changes amongst them. The awareness campaigns are included explicitly as a separate dynamic variable in the modeling process. The model is analyzed qualitatively using stability theory of differential equations. We have also identified an optimal implementation rate of awareness campaigns so that disease can be controlled with minimal possible expenditure on awareness campaigns, using optimal control theory. The control setting is investigated analytically using optimal control theory, and the numerical solutions illustrating the optimal regimens under various assumptions are also shown. PMID- 26551552 TI - Leukocyte Trafficking to the Small Intestine and Colon. AB - Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein-coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin alpha4beta7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation. PMID- 26551558 TI - Cicada Wing Surface Topography: An Investigation into the Bactericidal Properties of Nanostructural Features. AB - Recently, the surface of the wings of the Psaltoda claripennis cicada species has been shown to possess bactericidal properties and it has been suggested that the nanostructure present on the wings was responsible for the bacterial death. We have studied the surface-based nanostructure and bactericidal activity of the wings of three different cicadas (Megapomponia intermedia, Ayuthia spectabile and Cryptotympana aguila) in order to correlate the relationship between the observed surface topographical features and their bactericidal properties. Atomic force microscopy and scanning electron microscopy performed in this study revealed that the tested wing species contained a highly uniform, nanopillar structure on the surface. The bactericidal properties of the cicada wings were investigated by assessing the viability of autofluorescent Pseudomonas fluorescens cells following static adhesion assays and targeted dead/live fluorescence staining through direct microscopic counting methods. These experiments revealed a 20-25% bacterial surface coverage on all tested wing species; however, significant bactericidal properties were observed in the M. intermedia and C. aguila species as revealed by the high dead:live cell ratio on their surfaces. The combined results suggest a strong correlation between the bactericidal properties of the wings and the scale of the nanotopography present on the different wing surfaces. PMID- 26551559 TI - Update on pathology, staging and molecular pathology of endometrial (uterine corpus) adenocarcinoma. AB - Endometrial carcinoma is comprised of two major groups: type I that is hormonally driven with a good prognosis and type II that is hormone independent with a poor prognosis. The two most common subtypes are endometrioid adenocarcinoma, the prototypic type I cancer, and uterine serous carcinoma, the prototypic type II cancer, each with their own distinct precursor lesion. The histologic type, as codified by the WHO Tumor Classification system, grade, and stage are used to guide treatment. There is an increasing interest in screening for familial risk factors, specifically Lynch syndrome. A molecular classification of endometrial cancers holds promise for future improvements in care. PMID- 26551560 TI - Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development. AB - Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of enhancer of zeste homolog 2 (EZH2)-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in cell cycle regulation, germline development and embryogenesis. Notably, the H3K9me2 modification extends to active enhancer elements where it promotes developmentally-linked gene silencing and directly marks promoters and gene bodies. This epigenetic mechanism is important for priming gene regulatory networks for critical cell fate decisions in rapidly proliferating postimplantation epiblast cells. PMID- 26551561 TI - Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch. AB - Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells--including germline stem cells--become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions--GLP-1/Notch signaling--becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance. PMID- 26551562 TI - Propagated infra-slow intrinsic brain activity reorganizes across wake and slow wave sleep. AB - Propagation of slow intrinsic brain activity has been widely observed in electrophysiogical studies of slow wave sleep (SWS). However, in human resting state fMRI (rs-fMRI), intrinsic activity has been understood predominantly in terms of zero-lag temporal synchrony (functional connectivity) within systems known as resting state networks (RSNs). Prior rs-fMRI studies have found that RSNs are generally preserved across wake and sleep. Here, we use a recently developed analysis technique to study propagation of infra-slow intrinsic blood oxygen level dependent (BOLD) signals in normal adults during wake and SWS. This analysis reveals marked changes in propagation patterns in SWS vs. wake. Broadly, ordered propagation is preserved within traditionally defined RSNs but lost between RSNs. Additionally, propagation between cerebral cortex and subcortical structures reverses directions, and intra-cortical propagation becomes reorganized, especially in visual and sensorimotor cortices. These findings show that propagated rs-fMRI activity informs theoretical accounts of the neural functions of sleep. PMID- 26551563 TI - Neuromodulation of excitatory synaptogenesis in striatal development. AB - Dopamine is released in the striatum during development and impacts the activity of Protein Kinase A (PKA) in striatal spiny projection neurons (SPNs). We examined whether dopaminergic neuromodulation regulates activity-dependent glutamatergic synapse formation in the developing striatum. Systemic in vivo treatment with Galphas-coupled G-protein receptors (GPCRs) agonists enhanced excitatory synapses on direct pathway striatal spiny projection neurons (dSPNs), whereas rapid production of excitatory synapses on indirect pathway neurons (iSPNs) required the activation of Galphas GPCRs in SPNs of both pathways. Nevertheless, in vitro Galphas activation was sufficient to enhance spinogenesis induced by glutamate photolysis in both dSPNs and iSPNs, suggesting that iSPNs in intact neural circuits have additional requirements for rapid synaptic development. We evaluated the in vivo effects of enhanced glutamate release from corticostriatal axons and postsynaptic PKA and discovered a mechanism of developmental plasticity wherein rapid synaptogenesis is promoted by the coordinated actions of glutamate and postsynaptic Galphas-coupled receptors. PMID- 26551564 TI - A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. AB - Small G-proteins of the ADP-ribosylation-factor-like (Arl) subfamily have been shown to be crucial to ciliogenesis and cilia maintenance. Active Arl3 is involved in targeting and releasing lipidated cargo proteins from their carriers PDE6delta and UNC119a/b to the cilium. However, the guanine nucleotide exchange factor (GEF) which activates Arl3 is unknown. Here we show that the ciliary G protein Arl13B mutated in Joubert syndrome is the GEF for Arl3, and its function is conserved in evolution. The GEF activity of Arl13B is mediated by the G-domain plus an additional C-terminal helix. The switch regions of Arl13B are involved in the interaction with Arl3. Overexpression of Arl13B in mammalian cell lines leads to an increased Arl3.GTP level, whereas Arl13B Joubert-Syndrome patient mutations impair GEF activity and thus Arl3 activation. We anticipate that through Arl13B's exclusive ciliary localization, Arl3 activation is spatially restricted and thereby an Arl3.GTP compartment generated where ciliary cargo is specifically released. PMID- 26551566 TI - Mast cell, the peculiar member of the immune system: A homeostatic aspect. AB - The mast cell is a member of the immune system having a basic role in allergic (anaphylactic) reactions. However, it contains, synthesizes, stores and secretes lots of substances, which initiates other reactions or participates in them. These are in connection with the deterioration of tissue correlation, as malignant tumors, angiogenesis, wound healing, pregnancy and different pathological conditions. In addition - as other members of the immune system - mast cells can synthesize, store and secrete hormones characteristic to the endocrine glands and can transport them to the site of requirement (packed transport), or produce and employ them locally. The effect of mast cells is controversial and frequently dual, stimulatory or inhibitory to the same organ or process. This is likely due to the heterogeneity of the mast cells, in morphology and cell content alike and dependent on the actual condition of the targeted tissue. The cells are transported in an unmatured form by the blood circulation and are exposed to microenvironmental effects, which influence their maturation. Their enrichment around tumors suggested using them as targets for tumor therapy more than fifty years ago (by the author), however, this idea lives its renaissance now. The review discusses the facts and ideas critically. PMID- 26551567 TI - Identification and characterization of CTX-M-15 producing Klebsiella pneumoniae clone ST101 in a Hungarian university teaching hospital. AB - We investigated the molecular epidemiology of extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae isolates derived from the teaching hospitals of University of Pecs, Pecs, Hungary in the time period 2004-2008. Molecular typing, antimicrobial susceptibility testing, detection of common beta lactamase genes (bla(CTX-M), bla(TEM) and bla(SHV)) and virulence associated traits (hypermucoviscosity, magA, k2a, rmpA, siderophores, type 1 and 3 fimbria, biofilm formation, serum resistance) were performed for 102 isolates. The results showed the presence of three major ciprofloxacin resistant CTX-M-15 producing clones (ST15 n = 69, ST101 n = 10, and ST147 n = 9), of which ST15 was predominant and universally widespread. Considering distribution in time and place, ST101 and ST147 were detected at fewer inpatient units and within a narrower time frame, as compared to ST15. Beside major clones, eleven minor clones were identified, and were shown to harbour the following beta-lactamase genes: six clones carried bla(CTX-M), four clones harboured bla(SHV-5) and one clone possessed both bla(CTX-M) and ESBL type bla(SHV). Among the SHV-5 producing K. pneumoniae clones a novel sequence type was found, namely ST1193, which harboured a unique infB allele. Different virulence factor content and peculiar antimicrobial susceptibility profile were characteristic for each clone. In contrast to major clone isolates, which showed high level resistance to ciprofloxacin, minor clone isolates displayed significantly lower MIC values for ciprofloxacin suggesting a role for fluoroquinolones in the dissemination of the major K. pneumoniae clones. This is the first description of the CTX-M-15 producing K. pneumoniae clone ST101 in Hungary. PMID- 26551565 TI - APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses. AB - The amyloid precursor protein (APP), whose mutations cause familial Alzheimer's disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a gamma-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer's disease, alterations of this synaptic role of APP could contribute to dementia. PMID- 26551568 TI - Diversity of Cryphonectria parasitica populations from the Carpathian Basin. AB - The ascomycetous fungus Cryphonectria parasitica (Murr.) is one of the most important fungal pathogens of chestnut (Castanea sativa Mill.), causing chestnut blight. It is originated from Eastern Asia and was introduced into North America, and later into Europe. Almost 100 C. parasitica isolates were collected mainly from the Carpathian Basin to study their diversity and phylogenetic relationships. Three nuclear molecular markers were tested: (i) internal transcribed spacers (ITS), (ii) translation elongation factor 1 subunit alpha (tef1), and (iii) six microsatellite loci. The ITS region proved to be highly polymorphic but this kind of variability did not reflect the geographical regions of the isolates, while the tef1 sequences were identical in all isolates. Microsatellite haplotype diversity was relatively high (0.923-0.984) calculated for the fungal populations of the Carpathian Basin. This may have resulted from the multiple introductions from diverse origins of the populations, close to the first site of observation in Northern Italy. The BAPS analysis of the microsatellite markers occasionally grouped together samples from remote geographical origin, suggesting human assistance in the introduction of new C. parasitica haplotypes from distinct areas. PMID- 26551569 TI - Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report. AB - The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively. PMID- 26551570 TI - Study of Th1/Th2 balance in peripheral blood mononuclear cells of patients with alopecia areata. AB - Alopecia areata represents an autoimmune pathological process driven primarily by cellular aberrations contained within the immune system, which activates various humoral and cellular elements of the immune response. The aim of this study was to determine the mRNA expression levels of T-bet and GATA-3 as potential inducers of T helper (Th)1 and Th2 differentiation, respectively, as well as Th1(IFN gamma) and Th2(IL-4) cytokine mRNA expression in patients with alopecia areata. Using real-time reverse transcriptase PCR (RT-PCR), the relative amounts of T bet, GATA-3, IFN-gamma, and IL-4 mRNA transcripts were determined in PBMCs from 20 Iranian patients with alopecia areata and compared with those of 20 healthy control subjects. In comparison with the normal group, T-bet and IFN-gamma mRNA expression levels were significantly up-regulated in the alopecia areata patients, while GATA-3 and IL-4 mRNA expression levels were down-regulated. Notably, positive correlation (P < 0.05) was found between IFN-gamma and T-bet levels in patients and controls. In addition, significant positive correlations existed between GATA-3 and IL-4 (P < 0.05). These results indicate that a Th1/Th2 imbalance exists in alopecia areata, and it may be implicated in the pathogenesis of disease. PMID- 26551571 TI - Evaluation of antimicrobial resistance of Helicobacter pylori in the last 15 years in West Poland. AB - Increasing resistance to drugs represents a serious problem in treatment of infections with Helicobacter pylori, providing cause of frequent therapeutic failures. Present study aimed at analysis of changes in resistance of H. pylori to antibiotics in West Poland within the recent 15 years. 108 strains of H. pylori were analysed, isolated from gastric mucosa of adult patients. Group 1 involved 66 strains isolated in years of 1998/1999. Group 2 comprised 42 isolates obtained in years of 2013/2014. Susceptibility to amoxicillin (AMX), clarithromycin (CL), tetracycline (TC) and metronidazole (MTZ) was determined by E-test (AB Biodisc). All strains on both studied groups were susceptible to AMX. In group 1 all strains proved to be susceptible to TC, while 9% and 36% of tested strains were resistant to CL and MTZ, respectively. By contrast, in group 2, 31% and 83% of strains were resistant to CL and MTZ, respectively. In parallel, 14% strains were found to be resistant to TC (according to EUCAST interpretations). In West Poland, within recent 15 years a dramatic increase was noted in H. pylori strains resistant to metronidazole. In parallel, a significant increase was noted in proportion of strains resistant to clarithromycin. PMID- 26551572 TI - Antibiotic susceptibility of sulfamethoxazole-trimethoprim resistant Stenotrophomonas maltophilia strains isolated at a tertiary care centre in Hungary. AB - Sulfamethoxazole-trimethoprim (SXT) is the drug-of-choice in Stenotrophomonas maltophilia caused infections. There has been an increase in resistance to SXT of S. maltophilia over recent years. In this study 30 S. maltophilia clinical isolates resistant to SXT were investigated. Antibiotic susceptibilities for ciprofloxacin, moxifloxacin, levofloxacin, doxycycline, tigecycline, ceftazidime, colistin and chloramphenicol were determined by broth microdilution method. None of the strains were susceptible to ciprofloxacin, tigecycline, ceftazidime or colistin. Only 37% of the isolates were susceptible to levofloxacin or moxifloxacin. Two isolates resistant to all tested antibiotic agents and two others susceptible only to doxycycline were further investigated: susceptibility for combinations of antibiotics was analyzed by checkerboard technique. According to the fractional inhibitory concentration indices calculated, moxifloxacin plus ceftazidime combination was found to be synergistic in each case. Genetic testing revealed the predominance of sul1 gene. Our study concluded that the range of effective antibiotic agents is even more limited in infections caused by SXT resistant S. maltophilia. In these cases, in vitro synergistic antibiotic combinations could be potential therapeutic options. PMID- 26551573 TI - Relationship between kinetics of growth and production of exo-electrons: Case study with Geobacter toluenoxydans. AB - Kinetics of growth and product formation of G. toluenoxydans DSMZ 19350 strain were investigated using sodium-acetate as substrate and Fe(3+)-ions and fumarate as electron acceptor. Response surface method was adapted for evaluation of growth of bacteria. Results showed that maximum growth was detected in the case of 2.2 g/L substrate concentration. Application of higher substrate concentration (>2.5 g/L sodium acetate) significantly inhibits the bacterial growth. Luong's model was found to be the most suitable to determine kinetic parameters (MU(max) = 0.033 1/h, KS = 0.205 g/L) of growth of G.toluenoxydans strain, and the growth was completely inhibited at substrate concentration higher than 3.1 g/L. In the case of product formation the Haldane model was used and kinetic parameters are MU(Pmax) = 0.123 mg/h, K(PS)= 0.184 g/L. Correlation between microbial growth and product formation was observed using the Luedeking-Piret empirical method. Both factors (growth and number of cells) affected significantly iron(III)-reduction, thus the product formation. These results are important and open the possibility to design a continuous MFC setting operating with G. toluenoxydans as biocatalyst. PMID- 26551574 TI - Significance of yeasts in bloodstream infection: Epidemiology and predisposing factors of Candidaemia in adult patients at a university hospital (2010-2014). AB - The incidence of Candida bloodstream infection (BSI) has increased during the past decades. Species distribution is changing worldwide, and non-albicans Candida spp. are becoming more prevalent. Acquired resistance to antifungal agents has been documented in several reports. The aim of our study was to assess the epidemiology and antifungal susceptibility of Candida isolates from BSI at our institute. The incidence of Candida BSI increased during the first four years of our investigation, from 1.7 to 3.5 episodes / 10 000 admissions, then dropped to 2.66 episodes / 10 000 admissions in the last year. The most frequently isolated species was C. albicans (63%), followed by C. glabrata (13%), C. parapsilosis (10.2%), C. tropicalis (9.3%), and C. krusei (3.7%). One isolate each of C. kefyr, C. fabianii and C. inconspicua were detected. The percentage of C. albicans remained stable throughout the study period. The most frequent risk factors of Candida BSI in our patient population were intensive care treatment (60.4%), abdominal surgery (52.5%), and solid malignancy (30.7%). All isolates were wild-type organisms, no acquired antifungal resistance was detected. PMID- 26551575 TI - Single-cell technologies to study the immune system. AB - The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. PMID- 26551576 TI - Nuclear organization of some immunohistochemically identifiable neural systems in two species of the Euarchontoglires: A Lagomorph, Lepus capensis, and a Scandentia, Tupaia belangeri. AB - The present study describes the organization of the nuclei of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of two members of Euarchontoglires, Lepus capensis and Tupaia belangeri. The aim of the present study was to investigate the nuclear complement of these neural systems in comparison to previous studies on Euarchontoglires and generally with other mammalian species. Brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei revealed in the current study were similar between the species investigated and to mammals generally, but certain differences in the nuclear complement highlight potential phylogenetic interrelationships within the Euarchontoglires and across mammals. In the northern tree shrew the nucleus of the trapezoid body contained neurons immunoreactive to the choline acetyltransferase antibody with some of these neurons extending into the lamellae within the superior olivary nuclear complex (SON). The cholinergic nature of the neurons of this nucleus, and the extension of cholinergic neurons into the SON, has not been noted in any mammal studied to date. In addition, cholinergic neurons forming the medullary tegmental field were also present in the northern tree shrew. Regarding the catecholaminergic system, the cape hare presented with the rodent specific rostral dorsal midline medullary nucleus (C3), and the northern tree shrew lacked both the ventral and dorsal divisions of the anterior hypothalamic group (A15v and A15d). Both species were lacking the primate/megachiropteran specific compact portion of the locus coeruleus complex (A6c). The nuclei of the serotonergic and orexinergic systems of both species were similar to those seen across most Eutherian mammals. Our results lend support to the monophyly of the Glires, and more broadly suggest that the megachiropterans are more closely related to the primates than are any other members of Euarchontoglires studied to date. PMID- 26551577 TI - Object-based attentional facilitation and inhibition are neuropsychologically dissociated. AB - Salient peripheral cues produce a transient shift of attention which is superseded by a sustained inhibitory effect. Cueing part of an object produces an inhibitory cueing effect (ICE) that spreads throughout the object. In dynamic scenes the ICE stays with objects as they move. We examined object-centred attentional facilitation and inhibition in a patient with visual form agnosia. There was no evidence of object-centred attentional facilitation. In contrast, object-centred ICE was observed in 3 out of 4 tasks. These inhibitory effects were strongest where cues to objecthood were highly salient. These data are evidence of a neuropsychological dissociation between the facilitatory and inhibitory effects of attentional cueing. From a theoretical perspective the findings suggest that 'grouped arrays' are sufficient for object-based inhibition, but insufficient to generate object-centred attentional facilitation. PMID- 26551578 TI - A Simple and Universal Technique To Extract One- and Two-Dimensional Nanomaterials from Contaminated Water. AB - We demonstrate a universal approach to extract one- and two-dimensional nanomaterials from contaminated water, which is based on a microscopic oil-water interface trapping mechanism. Results indicate that carbon nanotubes, graphene, boron nitride nanotubes, boron nitride nanosheets, and zinc oxide nanowires can be successfully extracted from contaminated water at a successful rate of nearly 100%. The effects of surfactants, particle shape, and type of organic extraction fluids are evaluated. The proposed extraction mechanism is also supported by in situ monitoring of the extraction process. We believe that this extraction approach will prove important for the purification of water contaminated by nanoparticles and will support the widespread adoption of nanomaterial applications. PMID- 26551579 TI - A Cathodic "Signal-off" Photoelectrochemical Aptasensor for Ultrasensitive and Selective Detection of Oxytetracycline. AB - A novel cathodic "signal-off" strategy was proposed for photoelectrochemical (PEC) aptasensing of oxytetracycline (OTC). The PEC sensor was constructed by employing a p-type semiconductor BiOI doped with graphene (G) as photoactive species and OTC-binding aptamer as a recognition element. The morphological structure and crystalline phases of obtained BiOI-G nanocomposites were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The UV-visible absorption spectroscopic analysis indicated that doping of BiOI with graphene improved the absorption of materials in the visible light region. Moreover, graphene could facilitate the electron transfer of BiOI modified electrode. As a result, the cathodic photocurrent response of BiOI under visible light irradiation was significantly promoted when a suitable amount of graphene was doped. When amine-functionalized OTC-binding aptamer was immobilized on the BiOI-G modified electrode, a cathodic PEC aptasensor was fabricated, which exhibited a declined photocurrent response to OTC. Under the optimized conditions, the photocurrent response of aptamer/BiOI-G/FTO was linearly proportional to the concentration of OTC ranging from 4.0 to 150 nM, with a detection limit (3S/N) of 0.9 nM. This novel PEC sensing strategy demonstrated an ultrasensitive method for OTC detection with high selectivity and good stability. PMID- 26551580 TI - Isolated Right Vein of Labbe Thrombosis. PMID- 26551581 TI - Conformation and Aggregation of LKalpha14 Peptide in Bulk Water and at the Air/Water Interface. AB - Historically, the protein folding problem has mainly been associated with understanding the relationship between amino acid sequence and structure. However, it is known that both the conformation of individual molecules and their aggregation strongly depend on the environmental conditions. Here, we study the aggregation behavior of the model peptide LKalpha14 (with amino acid sequence LKKLLKLLKKLLKL) in bulk water and at the air/water interface. We start by a quantitative analysis of the conformational space of a single LKalpha14 in bulk water. Next, in order to analyze the aggregation tendency of LKalpha14, by using the umbrella sampling technique we calculate the potential of mean force for pulling a single peptide from an n-molecule aggregate. In agreement with the experimental results, our calculations yield the optimal aggregate size as four. This equilibrium state is achieved by two opposing forces: Coulomb repulsion between the lysine side chains and the reduction of solvent accessible hydrophobic surface area upon aggregation. At the vacuum/water interface, however, even dimers of LKalpha14 become marginally stable, and any larger aggregate falls apart instantaneously. Our results indicate that even though the interface is highly influential in stabilizing the alpha-helix conformation for a single molecule, it significantly reduces the attraction between two LKalpha14 peptides, along with their aggregation tendency. PMID- 26551582 TI - A framework for energy use indicators and their reporting in life cycle assessment. AB - Energy use is a common impact category in life cycle assessment (LCA). Many different energy use indicators are used in LCA studies, accounting for energy use in different ways. Often, however, the choice behind which energy use indicator is applied is poorly described and motivated. To contribute to a more purposeful selection of energy use indicators and to ensure consistent and transparent reporting of energy use in LCA, a general framework for energy use indicator construction and reporting in LCA studies will be presented in this article. The framework differentiates between 1) renewable and nonrenewable energies, 2) primary and secondary energies, and 3) energy intended for energy purposes versus energy intended for material purposes. This framework is described both graphically and mathematically. Furthermore, the framework is illustrated through application to a number of energy use indicators that are frequently used in LCA studies: cumulative energy demand (CED), nonrenewable cumulative energy demand (NRCED), fossil energy use (FEU), primary fossil energy use (PFEU), and secondary energy use (SEU). To illustrate how the application of different energy use indicators may lead to different results, cradle-to-gate energy use of the bionanomaterial cellulose nanofibrils (CNF) is assessed using 5 different indicators and showing a factor of 3 differences between the highest and lowest results. The relevance of different energy use indicators to different actors and contexts will be discussed, and further developments of the framework are then suggested. Integr Environ Assess Manag 2016;12:429-436. (c) 2015 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC. PMID- 26551583 TI - Trends in Ambulatory Self-Report: The Role of Momentary Experience in Psychosomatic Medicine: Erratum. PMID- 26551584 TI - Mental Stress-Induced Ischemia in Patients With Coronary Artery Disease: Echocardiographic Characteristics and Relation to Exercise-Induced Ischemia: Erratum. PMID- 26551585 TI - FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma. AB - OBJECTIVE: The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). METHODS: FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy. RESULTS: The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC. CONCLUSION: FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC. PMID- 26551586 TI - Radon in spring waters in the south of Catalonia. AB - Spring waters in the south of Catalonia were analysed to determine the (222)Rn activity in order to be able to establish a correlation between the obtained values with the geology of the area of origin of these samples, and also estimate the potential health risks associated with (222)Rn. Most of the analysed samples (90%) show (222)Rn activities lower than 100Bq/L (exposure limit in water recommended by the World Health Organisation and EU directive 2013/51/EURATOM). However, in some cases, the activity values found for this isotope exceeded those levels and this can be attributed to the geology of the area where the spring waters are located, which is predominantly of granitic characteristics. To verify the origin of the radon present in the analysed samples, the obtained activity values were compared with the activities of its parents ((226)Ra, (238)U and (234)U). Finally, we have calculated the annual effective dose from all the radionuclides measured in spring water samples. The results showed that the higher contribution due to spring water ingestion come from (222)Rn and (226)Ra. The resulting contribution to the annual effective dose due to radon ingestion varies between 10.2 and 765.8 MUSv/y, and the total annual effective dose due to his parents, (226)Ra, (234)U and (238)U varies between 0.8 and 21.2 MUSv/y so the consumption of these waters does not involve any risks to population due to its natural radioactivity content. PMID- 26551587 TI - Tritium levels in milk in the vicinity of chronic tritium releases. AB - Tritium is the radioactive isotope of hydrogen. It can be integrated into most biological molecules. Even though its radiotoxicity is weak, the effects of tritium can be increased following concentration in critical compartments of living organisms. For a better understanding of tritium circulation in the environment and to highlight transfer constants between compartments, we studied the tritiation of different agricultural matrices chronically exposed to tritium. Milk is one of the most frequently monitored foodstuffs in the vicinity of points known for chronic release of radionuclides firstly because dairy products find their way into most homes but also because it integrates deposition over large areas at a local scale. It is a food which contains all the main nutrients, especially proteins, carbohydrates and lipids. We thus studied the tritium levels of milk in chronic exposure conditions by comparing the tritiation of the main hydrogenated components of milk, first, component by component, then, sample by sample. Significant correlations were found between the specific activities of drinking water and free water of milk as well as between the tritium levels of cattle feed dry matter and of the main organic components of milk. Our findings stress the importance of the metabolism on the distribution of tritium in the different compartments. Overall, dilution of hydrogen in the environmental compartments was found to play an important role dimming possible isotopic effects even in a food chain chronically exposed to tritium. PMID- 26551588 TI - Soil radon dynamics in the Amer fault zone: An example of very high seasonal variations. AB - Soil radon levels of the Amer fault zone have been measured for a 4 year-period with the aim of checking seasonal fluctuations obtained in previous studies and to understand radon origin and dynamics. In this manuscript additional results are presented: updated continuous and integrated soil radon measurements, radionuclide content of soil materials and a detailed analysis of an urban profile by means of the electrical resistivity imaging technique and punctual soil radon, thoron and CO2 measurements. Integrated and continuous measurements present a wide range of values, [0.2-151.6] kBq m(-3) for radon, [4.5-39.6] kBq m(-3) for thoron and [4.0-71.2] g m(-2) day(-1) for CO2. The highest soil radon levels in the vicinity of the Amer fault (>40 kBq m(-3)) are found close to the fractured areas and present very important fluctuations repeated every year, with values in summer much higher than in winter, confirming previous studies. The highest radon values, up to 150 kBq m(-3), do not have a local origin because the mean value of radium concentration in this soil (19 +/- 5 Bq kg(-1)) could not explain these values. Then soil radon migration through the fractures, influenced by atmospheric parameters, is assumed to account for such a high seasonal fluctuation. As main conclusion, in fractured areas, seasonal variations of soil radon concentration can be very important even in places where average soil radon concentration and radium content are not especially high. In these cases the migration capability of the soil is given not by intrinsic permeability but by the fracture structure. Potential risk estimation based on soil radon concentration and intrinsic permeability must be complemented with geological information in fractured systems. PMID- 26551590 TI - Vertical Flow Lithography for Fabrication of 3D Anisotropic Particles. AB - A microfluidics-based method for the 3D fabrication of anisotropic particles is reported. The method uses a vertical microchannel where tunable light patterns solidify photocurable resins for stacking multiple layers of the resins, thus enabling an application of stereolithography concepts to conventional flow lithography. Multilayered, tapered, and angular compartmental microparticles are demonstrated. PMID- 26551589 TI - Molecular docking and structure-based virtual screening studies of potential drug target, CAAX prenyl proteases, of Leishmania donovani. AB - Targeting CAAX prenyl proteases of Leishmania donovani can be a good approach towards developing a drug molecule against Leishmaniasis. We have modeled the structure of CAAX prenyl protease I and II of L. donovani, using homology modeling approach. The structures were further validated using Ramachandran plot and ProSA. Active site prediction has shown difference in the amino acid residues present at the active site of CAAX prenyl protease I and CAAX prenyl protease II. The electrostatic potential surface of the CAAX prenyl protease I and II has revealed that CAAX prenyl protease I has more electropositive and electronegative potentials as compared CAAX prenyl protease II suggesting significant difference in their activity. Molecular docking with known bisubstrate analog inhibitors of protein farnesyl transferase and peptidyl (acyloxy) methyl ketones reveals significant binding of these molecules with CAAX prenyl protease I, but comparatively less binding with CAAX prenyl protease II. New and potent inhibitors were also found using structure-based virtual screening. The best docked compounds obtained from virtual screening were subjected to induced fit docking to get best docked configurations. Prediction of drug-like characteristics has revealed that the best docked compounds are in line with Lipinski's rule. Moreover, best docked protein-ligand complexes of CAAX prenyl protease I and II are found to be stable throughout 20 ns simulation. Overall, the study has identified potent drug molecules targeting CAAX prenyl protease I and II of L. donovani whose drug candidature can be verified further using biochemical and cellular studies. PMID- 26551591 TI - Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: A two-center study. AB - BACKGROUND: The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue. MATERIAL AND METHODS: We studied 212 consecutive patients (age 72.5 +/- 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve. RESULTS: CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without. CONCLUSION: The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology. PMID- 26551593 TI - Creating Drug Solubilization Compartments via Phase Separation in Multicomponent Buccal Patches Prepared by Direct Hot Melt Extrusion-Injection Molding. AB - Creating in situ phase separation in solid dispersion based formulations to allow enhanced functionality of the dosage form, such as improving dissolution of poorly soluble model drug as well as being mucoadhesive, can significantly maximize the in vitro and in vivo performance of the dosage form. This formulation strategy can benefit a wide range of solid dosage forms for oral and alternative routes of delivery. This study using buccal patches as an example created separated phases in situ of the buccal patches by selecting the excipients with different miscibility with each other and the model drug. The quaternary dispersion based buccal patches containing PEG, PEO, Tween 80, and felodipine were prepared by direct hot melt extrusion-injection molding (HME-IM). The partial miscibility between Tween 80 and semicrystalline PEG-PEO led to the phase separation after extrusion. The Tween phases acted as drug solubilization compartments, and the PEG-PEO phase had the primary function of providing mucoadhesion and carrier controlled dissolution. As felodipine was preferably solubilized in the amorphous regions of PEG-PEO, the high crystallinity of PEG PEO resulted in an overall low drug solubilizing capacity. Tween 80 was added to improve the solubilization capacity of the system as the model drug showed good solubility in Tween. Increasing the drug loading led to the supersaturation of drug in Tween compartments and crystalline drug dispersed in PEG-PEO phases. The spatial distribution of these phase-separated compartments was mapped using X-ray micro-CT, which revealed that the domain size and heterogeneity of the phase separation increased with increasing the drug loading. The outcome of this study provides new insights into the applicability of in situ formed phase separation as a formulation strategy for the delivery of poorly soluble drugs and demonstrated the basic principle of excipient selection for such technology. PMID- 26551594 TI - Optimizing graph-based patterns to extract biomedical events from the literature. AB - IN BIONLP-ST 2013: We participated in the BioNLP 2013 shared tasks on event extraction. Our extraction method is based on the search for an approximate subgraph isomorphism between key context dependencies of events and graphs of input sentences. Our system was able to address both the GENIA (GE) task focusing on 13 molecular biology related event types and the Cancer Genetics (CG) task targeting a challenging group of 40 cancer biology related event types with varying arguments concerning 18 kinds of biological entities. In addition to adapting our system to the two tasks, we also attempted to integrate semantics into the graph matching scheme using a distributional similarity model for more events, and evaluated the event extraction impact of using paths of all possible lengths as key context dependencies beyond using only the shortest paths in our system. We achieved a 46.38% F-score in the CG task (ranking 3rd) and a 48.93% F score in the GE task (ranking 4th). AFTER BIONLP-ST 2013: We explored three ways to further extend our event extraction system in our previously published work: (1) We allow non-essential nodes to be skipped, and incorporated a node skipping penalty into the subgraph distance function of our approximate subgraph matching algorithm. (2) Instead of assigning a unified subgraph distance threshold to all patterns of an event type, we learned a customized threshold for each pattern. (3) We implemented the well-known Empirical Risk Minimization (ERM) principle to optimize the event pattern set by balancing prediction errors on training data against regularization. When evaluated on the official GE task test data, these extensions help to improve the extraction precision from 62% to 65%. However, the overall F-score stays equivalent to the previous performance due to a 1% drop in recall. PMID- 26551595 TI - Staff attributions of the causes of challenging behaviour in children and adults with profound intellectual and multiple disabilities. AB - A study has shown that staff do not generally perceive challenging behaviour in people with profound intellectual and multiple disabilities (PIMD) as being of serious consequence. In this study we aimed to gain a better understanding of the causal explanations that direct care and support staff give for challenging behaviour in this group. The purpose of this study was twofold: (1) to determine the way staff attribute challenging behaviour in children and adults with PIMD; and (2) to analyse whether more experienced staff attribute challenging behaviour in children and adults with PIMD differently than less experienced staff. In total, 195 direct support staff and an equal number of children and adults with PIMD participated in the study. Direct support staff filled out the Challenging behaviour Attribution Scale (five causal explanatory models of challenging behaviour) to explain challenging behaviour in one individual that they supported. The results show that direct support staff as a whole report the biomedical model as the most plausible explanation for challenging behaviour in children and adults with PIMD. However, in the present study the mean scores on all models are low. This might indicate that a large number of staff found none of the models particularly useful as possible explanations of challenging behaviour in people with PIMD. This could mean that staff have difficulties stating the cause of challenging behaviour in this group. Another possible explanation could be that there is little scientific knowledge about causing and maintaining factors of challenging behaviour in people with PIMD. It could also mean that staff have additional explanations for challenging behaviour in this target group that are not mentioned in the instrument used. Future research should address these issues. No differences were found between more experienced and less experienced direct support staff. PMID- 26551596 TI - Haptic-2D: A new haptic test battery assessing the tactual abilities of sighted and visually impaired children and adolescents with two-dimensional raised materials. AB - To fill an important gap in the psychometric assessment of children and adolescents with impaired vision, we designed a new battery of haptic tests, called Haptic-2D, for visually impaired and sighted individuals aged five to 18 years. Unlike existing batteries, ours uses only two-dimensional raised materials that participants explore using active touch. It is composed of 11 haptic tests, measuring scanning skills, tactile discrimination skills, spatial comprehension skills, short-term tactile memory, and comprehension of tactile pictures. We administered this battery to 138 participants, half of whom were sighted (n=69), and half visually impaired (blind, n=16; low vision, n=53). Results indicated a significant main effect of age on haptic scores, but no main effect of vision or Age * Vision interaction effect. Reliability of test items was satisfactory (Cronbach's alpha, alpha=0.51-0.84). Convergent validity was good, as shown by a significant correlation (age partialled out) between total haptic scores and scores on the B101 test (rp=0.51, n=47). Discriminant validity was also satisfactory, as attested by a lower but still significant partial correlation between total haptic scores and the raw score on the verbal WISC (rp=0.43, n=62). Finally, test-retest reliability was good (rs=0.93, n=12; interval of one to two months). This new psychometric tool should prove useful to practitioners working with young people with impaired vision. PMID- 26551597 TI - Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus. AB - Chemokines attract leukocytes to sites of infection in a G protein-coupled receptor (GPCR) and glycosaminoglycan (GAG) dependent manner. Therefore, chemokines are crucial molecules for proper functioning of our antimicrobial defense mechanisms. In addition, some chemokines have GPCR-independent defensin like antimicrobial activities against bacteria and fungi. Recently, high affinity for GAGs has been reported for the positively charged COOH-terminal region of the chemokine CXCL9. In addition to CXCL9, also CXCL12gamma has such a positively charged COOH-terminal region with about 50% positively charged amino acids. In this report, we compared the affinity of COOH-terminal peptides of CXCL9 and CXCL12gamma for GAGs and KD values in the low nM range were detected. Several enveloped viruses such as herpesviruses, hepatitis viruses, human immunodeficiency virus (HIV), dengue virus (DENV), etc. are known to bind to GAGs such as the negatively charged heparan sulfate (HS). In this way GAGs are important for the initial contacts between viruses and host cells and for the infection of the cell. Thus, inhibiting the virus-cell interactions, by blocking GAG-binding sites on the host cell, might be a way to target multiple virus families and resistant strains. This article reports that the COOH-terminal peptides of CXCL9 and CXCL12gamma have antiviral activity against DENV serotype 2, clinical and laboratory strains of herpes simplex virus (HSV)-1 and respiratory syncytial virus (RSV). Moreover, we show that CXCL9(74-103) competes with DENV envelope protein domain III for binding to heparin. These short chemokine-derived peptides may be lead molecules for the development of novel antiviral agents. PMID- 26551598 TI - Arginase-2 is cooperatively up-regulated by nitric oxide and histone deacetylase inhibition in human umbilical artery endothelial cells. AB - Arginase-2 counteracts endothelial nitric oxide synthase (eNOS) activity in human endothelium, and its expression is negatively controlled by histone deacetylase (HDAC2). Conversely NO inhibits HDAC and previous studies suggest that arginase-2 is up-regulated by NO. We studied whether NO regulates arginase-2 expression in umbilical artery endothelial cells (HUAEC) increasing ARG2 promoter accessibility. HUAEC exposed to NOC-18 (NO donor, 1-100 MUM, 0-24 h) showed an increase in arginase-2 but a decrease in eNOS mRNA levels in a time-dependent manner, with a maximal effect at 100 MUM (24 h). Conversely NOS inhibition with L NAME (100 MUM) reduced arginase-2 mRNA and protein levels, an effect reverted by co-incubation with NOC-18. Treatment with TSA paralleled the effects of NO on arginase-2 and eNOS at mRNA and protein levels, with maximal effect at 10 MUM. Co incubation of NOC-18 (100 MUM) with a sub-maximal concentration of TSA (1 MUM) potentiated the increase in arginase-2 mRNA levels, whilst L-NAME prevented TSA dependent arginase-2 induction. The effects on arginase-2 mRNA were paralleled by changes in chromatin accessibility, as well as increased levels of H3K9 and H4K12 acetylation, at ARG2 proximal (-579 to -367 and -280 to -73 bp from TSS) and core (-121 to +126 bp from TSS) promoter. Finally NO-dependent arginase-2 induction was prevented by pre-incubation for 10 min with the cysteine blocker MMTS (10 mM). These data showed for the first time that NO up-regulates arginase-2 expression in primary cultured human endothelial cells by an epigenetic-mediated mechanism increasing ARG2 promoter accessibility suggesting a negative regulatory loop for eNOS activity. PMID- 26551599 TI - Condensation-Driven Assembly of Boron-Containing Bis(Heteroaryl) Motifs Using a Linchpin Approach. AB - Herein, we describe the bromomethyl acyl boronate linchpin--an enabling reagent for the condensation-driven assembly of novel bis(heteroaryl) motifs. This building block is readily accessible from commercially available starting materials. A variety of 2-amino- and 2-methylpyridines were reacted with MIDA protected bromomethyl acylboronate to afford 2-boryl imidazo[1,2-a]pyridine and 2 boryl indolizine derivatives, respectively, in excellent yields. Subsequent condensation with hydroxyamidines and hydrazonamides converted the intermediate heterocycles into novel boron-containing bis(heteroaryl) units characterized by high thermal stability. PMID- 26551600 TI - A LONG-TERM FOLLOW-UP STUDY OF A RANDOMIZED CONTROLLED TRIAL OF MOTHER-INFANT PSYCHOANALYTIC TREATMENT: OUTCOMES ON MOTHERS AND INTERACTIONS. AB - An earlier randomized controlled trial (RCT) compared 80 mother-infant dyads in a Stockholm sample. One had received mother-infant psychoanalytic treatment [mother infant psychoanalytic therapies (MIP) group], and the other received Child Health Center care (CHCC group). Effects were found on mother-reported depression and expert-rated mother-infant relationship qualities and maternal sensitivity. When the children were 412 years, the dyads were followed up with assessments of the children's attachment representations, social and emotional development, and global functioning, and the mothers' psychological well-being and representations of the child as well as the mother-child interactions. We gathered data from 66 cases approximately 312 years' posttreatment. All scores involving the mothers had now approached community levels. We found effects on maternal depression in favor of MIP, but no other between-group differences. The MIP treatments seemed to have helped the mothers to recover more quickly on personal well-being, to become more sensitive to their babies' suffering, and to better support and appreciate their children throughout infancy and toddlerhood. If so, this would explain why the MIP children had a better global functioning and were more often "OK" and less often "Troubled" at 412 years. PMID- 26551602 TI - Nickel-Free Alternatives Raise Awareness. AB - Allergic contact dermatitis to nickel is a global health problem. Worldwide, nickel continues to be the most prevalent and relevant contact allergen detected in tested populations for the last 30 years. Thus, the need for nickel-free products is palpable. We present a sustainable resource to aid providers and consumers in locating a wide variety of nickel free alternatives. PMID- 26551603 TI - "Parabenoia" Debunked, or "Who's Afraid of Parabens?". AB - Parabens have been used as preservatives in foods, injectables, and topical preparations for nearly 10 decades. Present in nature, rapidly metabolized by skin and liver enzymes, they have an excellent safety record. However, in the past 15 years, they have been under scrutiny for their alleged estrogenic and antiandrogenic effects, as well as their putative role in promoting cancerogenesis through endocrine disruption. Scientific articles supporting these assertions have led the European Community to ban or restrict the use of some parabens. Despite that methylparaben and ethylparaben have negligible endocrine disruption activity, the food, pharmaceutical, and cosmetic industries are under pressure from scare campaigns in the media and are responding by replacing parabens with other biocides that cause multiple cases, and even worldwide epidemics, of allergic contact sensitization. In the present review, we present a balanced account of the published literature about the metabolism and potential toxicology of parabens. PMID- 26551604 TI - Epidermal Expression of Filaggrin/Profilaggrin Is Decreased in Atopic Dermatitis: Reverse Association With Mast Cell Tryptase and IL-6 but Not With Clinical Severity. AB - BACKGROUND: A decrease in filaggrin expression contributes to the pathogenesis of atopic dermatitis (AD) and can be modified by inflammatory factors. OBJECTIVES: The aim of this study was to determine the correlation of (pro)filaggrin (filaggrin and profilaggrin) expression with clinical severity in AD and with mast cell (MC) tryptase, chymase, and IL-6. METHODS: Punch biopsies were collected from 17 patients with moderate-to-severe AD and from 10 psoriatic patients. Atopic dermatitis severity was measured using different clinical parameters. (Pro)filaggrin, MC tryptase, chymase, and IL-6 were stained using immunohistochemical, enzymehistochemical, and sequential double-staining methods. RESULTS: (Pro)filaggrin expression was lower in the lesional than in the nonlesional granular layer in AD and was correlated negatively with itch severity but not with other severity parameters. (Pro)filaggrin expression was also decreased in the psoriatic lesions. In AD, (pro)filaggrin expression correlated negatively with the number of tryptase MCs in the nonlesional granular layer and with IL-6 MCs in both the nonlesional and lesional granular layers. CONCLUSION: (Pro)filaggrin expression is decreased in AD and is reversely associated with MC tryptase and IL-6. However, it does not associate with disease severity, and it was also decreased in psoriasis. PMID- 26551605 TI - Cutaneous Delayed-Type Hypersensitivity to Surfactants. AB - BACKGROUND: Repeated and prolonged use of surfactants can cause irritant as well as allergic contact dermatitis. OBJECTIVE: This study reports the frequency of positive patch test results to surfactants tested on the North American Contact Dermatitis Group screening series including cocamidopropyl betaine (CAPB), amidoamine (AA), dimethylaminopropylamine (DMAPA), oleamidopropyl dimethylamine (OPD), and cocamide diethanolamide (CDEA), and correlations of positive reactions between CAPB and the other surfactants. METHODS: This was a retrospective analysis of 10 877 patients patch tested between 2009 and 2014 to the surfactants CAPB, AA, DMAPA, OPD, and CDEA. Frequencies of positive reactions to these surfactants were calculated, and trends of reactivity between the surfactants analyzed. CONCLUSIONS: The OPD had the highest rate of positive patch reactions (2.3%) followed by DMAPA (1.7%), and CAPB (1.4%). The AA and CDEA had the lowest rate of positive reactions (0.8%). There was a high degree of overlap in positive patch tests between the surfactants. The CDEA was the least likely to coreact with another surfactant. PMID- 26551606 TI - Patch Testing for Metal Allergy With Manufacturer-Supplied Materials Before Nuss Bar Insertion. AB - INTRODUCTION: The increasing use of metal implantable devices has raised awareness of nickel allergy. Preoperative patch testing for patients with pectus excavatum (PE) with a known metal allergy or history of atopy is an accepted practice before the Nuss procedure. The Nuss bar manufacturer offers a metal disc for preoperative testing for metal sensitivities. However, the efficacy of this disc is not well understood. OBJECTIVE: The purpose of this study was to determine the sensitivity of the metal disc in detecting nickel allergy compared with that of standard patch testing. METHODS: Two PE patients were referred for preoperative patch testing with the metal disc to screen for metal allergy before the Nuss procedure. Based on our initial findings, 7 patients without PE scheduled for patch testing for the evaluation of chronic dermatitis were additionally tested with the metal disc if they were found to have risk factors for nickel allergy. All patch testing was performed according to set standards. CONCLUSIONS: The metal disc may not be adequately sensitive to determine nickel allergy before the Nuss procedure. Patch testing alone with standard formulations of nickel sulfate in petrolatum may be more sensitive in diagnosing nickel allergy. PMID- 26551607 TI - Occupational Contact Dermatitis: Workers' Compensation Patch Test Results of Portland, Oregon, 2005-2014. AB - BACKGROUND: Workers are exposed to potential irritants and allergens with constant introduction of new industrial chemicals in the workplace. OBJECTIVE: Characterize the final diagnoses, demographics, occupations, exposures, clinical presentations, patch test results, dermatologic histories, and risk factors of workers evaluated for suspected work-related allergic contact dermatitis (ACD). METHODS: A retrospective chart review of 310 workers' compensation independent medical examinations evaluated for suspected work-related ACD was performed. Workers were seen in a community dermatology clinic in Portland, Oregon, from 2005 to 2014. Evaluation included history, physical examination, patch testing, and further diagnostic workup when indicated. RESULTS: Hand dermatitis was the most common presentation (n = 148, 47.7%). Prevalent occupations included health care workers (n = 51, 16.5%), custodial staff (n = 41, 13.2%), and machinists (n = 36, 11.6%). Allergic contact dermatitis (47.5%) was more common than irritant contact dermatitis (ICD) (38.9%) in those diagnosed as having occupational skin disease (n = 185). The highest-frequency work-related allergens were thiuram mix (21 of 88, 23.9%), carba mix (20 of 88, 22.7%), potassium dichromate (9 of 88, 10.2%), and epoxy resin (9 of 88, 10.2%). CONCLUSIONS: Allergic contact dermatitis and ICD are common occupational skin disorders. In this population of workers' compensation referrals, ACD was more common, with 73.3% of those cases work related, compared with 86.7% of ICD. Blue collar work and wet work were risk factors for the development of ACD and ICD. PMID- 26551608 TI - Contact Allergy to Surfactants in a Hypoallergenic Liquid Cleanser. AB - : Surfactants are a relatively rare cause of allergic contact dermatitis (ACD) and testing patients to personal care products containing these ingredients has historically been difficult given their irritant properties. Using the semiopen technique, we were able to identify ACD to a hypoallergenic liquid cleanser in 2 patients who presented to our patch test clinic only months apart. Additional patch testing to individual ingredients led to subsequent identification of 3 novel surfactant allergens (sodium lauroyl sarcosinate, isostearamidopropyl morpholine lactate, and disodium lauroamphodiacetate). Only one of these allergens, sodium lauroyl sarcosinate, has previously been reported as a cause of ACD. PMID- 26551609 TI - Occupational Airborne Contact Dermatitis From Proton Pump Inhibitors. AB - Few published reports have described occupational contact dermatitis from proton pump inhibitor (PPI) exposure in the literature. We present an additional case of a 58-year-old male pharmaceutical worker with an occupational airborne allergic contact dermatitis to PPIs confirmed by patch testing. This is a novel report of workplace exposure to dexlansoprazole and esomeprazole PPIs with resultant clinical contact allergy and relevant positive patch test results to these 2 agents. A literature review of all previously reported cases of occupational contact dermatitis to PPI is summarized. The case also emphasizes the importance of even minute exposures when considering workplace accommodation. PMID- 26551610 TI - Erythroderma due to Unwitting Exposure to an Unobvious Allergen Source. PMID- 26551612 TI - Hyporeactive Products 2015: An Adjunct in the Treatment of Contact Dermatitis and Other Chronic Eczemas. PMID- 26551611 TI - Peri-Anal Ulcerations in a Patient With Essential Pruritus. PMID- 26551613 TI - Bilayer Effects of Antimalarial Compounds. AB - Because of the perpetual development of resistance to current therapies for malaria, the Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process. We tested the 80 most potent compounds from the box for bilayer-mediated effects on membrane protein conformational changes (a measure of likely toxicity) in a gramicidin-based stopped flow fluorescence assay. Among the Malaria Box compounds tested, four compounds altered membrane properties (p< 0.05); MMV007384 stood out as a potent bilayer perturbing compound that is toxic in many cell-based assays, suggesting that testing for membrane perturbation could help identify toxic compounds. In any case, MMV007384 should be approached with caution, if at all. PMID- 26551614 TI - Post-Synthesis Incorporation of 64Cu in CuS Nanocrystals to Radiolabel Photothermal Probes: A Feasible Approach for Clinics. AB - We report a simple method for the incorporation of Cu(I) or (64)Cu(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or (64)Cu(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of (64)Cu ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice. PMID- 26551615 TI - Applying Knowledge of Species-Typical Scavenging Behavior to the Search and Recovery of Mammalian Skeletal Remains. AB - Forensic investigations involving animal scavenging of human remains require a physical search of the scene and surrounding areas. However, there is currently no standard procedure in the U.K. for physical searches of scavenged human remains. The Winthrop and grid search methods used by police specialist searchers for scavenged remains were examined through the use of mock red fox (Vulpes vulpes) scatter scenes. Forty-two police specialist searchers from two different regions within the U.K. were divided between those briefed and not briefed with fox-typical scavenging information. Briefing searchers with scavenging information significantly affected the recovery of scattered bones (chi(2) = 11.45, df = 1, p = 0.001). Searchers briefed with scavenging information were 2.05 times more likely to recover bones. Adaptions to search methods used by searchers were evident on a regional level, such that searchers more accustom to a peri-urban to rural region recovered a higher percentage of scattered bones (58.33%, n = 84). PMID- 26551616 TI - Multiferroic Heterostructures Integrating Ferroelectric and Magnetic Materials. AB - Multiferroic heterostructures can be synthesized by integrating monolithic ferroelectric and magnetic materials, with interfacial coupling between electric polarization and magnetization, through the exchange of elastic, electric, and magnetic energy. Although the nature of the interfaces remains to be unraveled, such cross coupling can be utilized to manipulate the magnetization (or polarization) with an electric (or magnetic) field, known as a converse (or direct) magnetoelectric effect. It can be exploited to significantly improve the performance of or/and add new functionalities to many existing or emerging devices such as memory devices, tunable microwave devices, sensors, etc. The exciting technological potential, along with the rich physical phenomena at the interface, has sparked intensive research on multiferroic heterostructures for more than a decade. Here, we summarize the most recent progresses in the fundamental principles and potential applications of the interface-based magnetoelectric effect in multiferroic heterostructures, and present our perspectives on some key issues that require further study in order to realize their practical device applications. PMID- 26551617 TI - Genetic studies of Russian patients with amyotrophic lateral sclerosis. AB - Our objective was to search for mutations in genes SOD1, TARDBP, C9orf72, ANG, ATXN2 and VEGF in Russian patients with amyotrophic lateral sclerosis (ALS). A group of 208 Russian patients with ALS was examined. Molecular genetic analysis was conducted using direct sequencing, fragment analysis, and real-time PCR. We found eight different point mutations in the SOD1 gene, with the frequency of mutations being 50% in familial ALS and 3% in sporadic ALS. No mutations were found in exon 6 of the TARDBP gene; however, deletion c.715-126delG in intron 5 of TARDBP was over-represented in ALS patients compared to controls (38% vs. 26.6%; chi(2 )= 13.17; p = 0.002). Hexanucleotide repeat expansion of the C9orf72 gene was revealed in 2.5% of sporadic ALS patients. Mutations in the ANG gene were identified in 1.5% of sporadic ALS patients. The presence of an intermediate number (28-33) of GAC repeats in the ATXN2 gene was observed significantly more often in the study group compared to the control group (5% vs. 1.7%; chi(2 )= 3.89; p = 0.0486). In the cohort examined, we found an association between the disease and the risk A-allele and the A/A genotype at the -2578S/A locus of the VEGF gene. In conclusion, we determined for the first time the genetic basis of ALS in a Russian population. PMID- 26551618 TI - Predictive Value of Cytokeratin 7 Immunohistochemistry in Cervical Low-grade Squamous Intraepithelial Lesion as a Marker for Risk of Progression to a High grade Lesion. AB - The squamocolumnar junction (SCJ) cell population of the uterine cervix is a discrete epithelial area and the putative source of the majority of high-grade squamous intraepithelial lesions (HSIL). The SCJ cells can be identified by immunohistochemical (IHC) stains including cytokeratin 7 (CK7). Others have theorized that an SCJ marker-positive low-grade squamous intraepithelial lesion (LSIL) has a higher risk for future HSIL compared with an SCJ marker-negative LSIL. This study has 2 aims: first, to refine the definition of a positive CK7 immunostaining pattern in cervical lesions, and, second, to test the hypothesis that CK7 positivity in LSIL indicates higher risk for future HSIL, with both questions addressed using a data set with consensus diagnoses. One hundred cases each of LSIL, moderate HSIL (CIN2), and severe HSIL (CIN3) were stained for CK7, with positivity defined as a diffuse cytoplasmic staining pattern (>5 to 6 contiguous cells); all others were considered negative. Using this model, 34% of CIN1, 45% of CIN2, and 60% of CIN3 were CK7 positive. With follow-up, CK7 positive LSILs were more likely to progress to HSIL compared with CK7-negative LSIL (32% vs. 11%, P=0.05), in concordance with the results of other researchers. This study simplifies cervical CK7 IHC grading into a reproducible system and supports the thesis that CK7 positivity in LSIL is associated with increased risk for future HSIL. Larger cohorts using consensus-diagnosed LSIL are needed to confirm these results before CK7 may be considered for clinical validation. PMID- 26551619 TI - Papillary Immature Metaplasia of the Anal Canal: A Low-grade Lesion That Can Mimic a High-grade Lesion. AB - In a natural history study of anal human papillomavirus (HPV) infection and HPV related lesions among homosexual men in Sydney, Australia, we identified 15 examples of papillary immature metaplasia (PIM) in anal biopsy samples. PIM has previously been described in the cervix, but not in the anal canal. PIM is a form of exophytic low-grade squamous intraepithelial lesion (eLSIL) also known as condyloma. In contrast to the maturing keratinocytes and koilocytosis seen in conventional eLSIL, the slender papillary structures of PIM have a surface population of immature squamous cells. In our anal samples PIM was characterized by close proximity to conventional eLSIL, was negative for p16 (p16) expression, and revealed the presence of a single low-risk HPV genotype (either 6 or 11) in laser capture microdissected lesions. The clinical significance of recognizing PIM lies in preventing misdiagnosis as high-grade squamous intraepithelial lesion, (the presumed precursor to anal cancer), due to the morphologic immaturity of the cell population. In routine practice, awareness of anal canal PIM and p16 immunostaining will prevent this. Further study of the natural history of anal canal PIM is needed. PMID- 26551620 TI - Broadening the Morphologic Spectrum of Bartonella henselae Lymphadenitis: Analysis of 100 Molecularly Characterized Cases. AB - Bartonella henselae lymphadenitis, or cat-scratch lymphadenitis (CSL), is classically associated with stellate microabscesses, occasional giant cells, and extension of the inflammatory infiltrate into perinodal soft tissue. Availability of B. henselae molecular testing on tissue specimens has broadened our understanding of the morphologic variation in this disease. Here we sought to describe the histopathologic features of the largest series to date of molecularly proven CSL. B. henselae polymerase chain reaction-positive tissue specimens from 2010 to 2012 were identified, and hematoxylin and eosin slides were reviewed. A single-step 16S-23S rRNA-based polymerase chain reaction testing was used to identify B. henselae on formalin-fixed, paraffin-embedded tissues. A total of 100 B. henselae-positive cases were identified. The median age of the patients was 26.5 years (range, 1 to 69 y). Ninety-two percent of cases presented in lymph nodes, with 66% of these occurring above the diaphragm, most commonly in the cervical chain. Of 100 cases, 57 had classical CSL features of necrotizing granulomas with microabscesses, with or without surrounding palisading histiocytes. In contrast, 43/100 cases lacked the prototypical microabscesses of CSL including: 23 cases (53.5%) with features of fungal/mycobacterial lymphadenitis, 6 (14%) cases with features of Kikuchi lymphadenitis, and 4 cases (9.3%) with the classic histologic triad of toxoplasma lymphadenitis. In summary, B. henselae lymphadenitis may lack the typical microabscesses in almost half of cases and may closely mimic other reactive, especially infectious, lymphadenopathies. Given the lack of specificity of many of these features, a low threshold for B. henselae molecular testing on tissue is warranted in the appropriate clinical context. PMID- 26551621 TI - Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors. AB - Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC. PMID- 26551622 TI - SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type. AB - The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric adenocarcinomas showed any SATB2 staining. In a subset of tumors for which CK7, CK20, and CDX2 were available, SATB2 was never positive in any tumor of any origin that was CK7+CK20-CDX2-. Among tumors that coexpressed all 3 markers (CK7+CK20+CDX2+), 6/7 SATB2 tumors were of colorectal or appendiceal origin, and 1/7 was a primary ovarian borderline tumor. We conclude that ovarian tumors with mucinous or endometrioid features that express SATB2 are unlikely to be of primary ovarian origin unless there is a component of mature teratoma in the ovary; instead, attention should be directed to a colorectal or appendiceal origin. SATB2 may be of particular value in ovarian mucinous tumors that are positive for all 3 markers (CK7+CK20+CDX2+), as SATB2 staining strongly implicates a colorectal or appendiceal origin. PMID- 26551623 TI - SWI/SNF Complex-deficient Undifferentiated/Rhabdoid Carcinomas of the Gastrointestinal Tract: A Series of 13 Cases Highlighting Mutually Exclusive Loss of SMARCA4 and SMARCA2 and Frequent Co-inactivation of SMARCB1 and SMARCA2. AB - Undifferentiated gastrointestinal tract carcinomas are rare highly aggressive neoplasms with frequent but not obligatory rhabdoid features. Recent studies showed loss of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin remodeling complex, in 50% of tested cases. However, the molecular pathways underlying histologically similar but SMARCB1-intact cases are unknown. We herein analyzed 13 cases for expression of 4 SWI/SNF complex subunits SMARCB1, SMARCA2, SMARCA4, and ARID1A and the mismatch-repair proteins MLH1, MSH2, MSH6, and PMS2 by immunohistochemistry. Patients included 12 men and 1 woman aged 32 to 81 years (median, 57 y). Site of origin was colon (5), small bowel (2), stomach (3), small+large intestine (1), small intestine+ampulla of Vater (1), and esophagogastric junction (1). All tumors showed anaplastic large to medium-sized cells with variable rhabdoid features, pleomorphic giant cells, and, rarely, spindle cell foci. Abortive gland formation was seen in 3 cases and bona fide glandular component in 1 case. Most cases strongly expressed vimentin and variably pancytokeratin. In total, 12/13 cases (92%) showed loss of at least 1 SWI/SNF component. Loss of SMARCB1 (5/13), SMARCA2 (10/13), SMARCA4 (2/13), and ARID1A (2/13) was observed either in combination or isolated. SMARCA2 loss was isolated in 5 cases and coexisted with lost SMARCB1 in 5 cases (all 5 SMARCB1 deficient tumors showed loss of SMARCA2 as well). Co-inactivation of SMARCB1 and SMARCA4 or of SMARCA2 and SMARCA4 was not observed. Two mismatch-repair-deficient cases (MLH1/PMS2) showed concurrent loss of SMARCB1, SMARCA2, and (one of them) ARID1A. This study illustrates for the first time loss of different components of the SWI/SNF complex other than SMARCB1 in undifferentiated gastrointestinal carcinomas including novel SMARCA4-deficient and SMARCA2-deficient cases. Our results underline the close link between SWI/SNF deficiency and the aggressive rhabdoid phenotype. Frequent loss of SMARCA2 possibly points to fragility/vulnerability of the SWI/SNF complex as a consequence of lost core subunit SMARCB1. The exact molecular mechanisms underlying co-inactivation of different SWI/SNF subunits merit further investigations. PMID- 26551624 TI - Enacted and implied stigma for dementia in a community in south-west Nigeria. AB - BACKGROUND: Dementia is a chronic progressive disease that mostly affects the elderly. There is often a stigma surrounding dementia patients because of poor awareness about the disease. In Nigeria, this stigma and related attitudes have not been fully explored. In this study, we assessed the attitude of people towards demented individuals in a transitional community in Nigeria. METHODS: The study used a mixed methods approach. Focused group discussions exploring the concept of dementia were conducted among six community groups, and quantitative data was obtained from an interviewer-administered questionnaire. A total of 313 respondents were selected with a cluster sampling technique. RESULTS: Only 212 respondents (67.7%) were aware of dementia. 'Memory loss disease', 'ageing disease', 'disease of insanity', 'brain disorder', 'disease of forgetfulness', and 'dull brain' are the common names used to describe dementia in the community. Enacted stigma was evident as 36% of respondents felt dementia was associated with shame and embarrassment in the community. Implied stigma was evident in another third that opined that demented individuals would prefer not to know or let others know that they have the disease. Also, 28% were of the opinion that people do not take those with dementia seriously. Of the 22 (10.4%) that reported having received structured information about dementia, 16 (72.7%) got the information from health facilities. Qualitative data revealed the presence of enacted stigma in the community as some referred to affected individuals by derogatory names such as 'madman'. Some statements from the focus group discussion participants also gave useful insights into the scorn with which demented individuals are sometimes treated. CONCLUSION: The presence of enacted and implied stigma related to dementia within the community calls for concern. More research efforts are needed to unravel the burden of stigma within communities and best practice for stigma-reducing interventions. PMID- 26551625 TI - Overview: A New Era of Cancer Genome in Myeloid Malignancies. AB - In the Myeloid session of the 30th Nagoya International Cancer Treatment Symposium, three speakers were invited. Prof. Clara Bloomfield emphasized the importance of genetic alterations for the prognostic stratification and treatment of acute myeloid leukemia (AML). Dr. Eytan Stein showed that there are promising anti-leukemia effects of IDH2 inhibitor, AG-221, and DOT1L inhibitor, EPZ-5676, based on early-phase clinical studies. Prof. Seishi Ogawa presented a review of the clonal dynamics of secondary myelodysplastic syndrome (MDS) derived from aplastic anemia (AA). From these presentations, we are confident that molecular analysis-based individualized therapies will be realized within a few years. PMID- 26551626 TI - Modeling the distinct phases of skill acquisition. AB - A focus of early mathematics education is to build fluency through practice. Several models of skill acquisition have sought to explain the increase in fluency because of practice by modeling both the learning mechanisms driving this speedup and the changes in cognitive processes involved in executing the skill (such as transitioning from calculation to retrieval). In the current study, we use hidden Markov modeling to identify transitions in the learning process. This method accounts for the gradual speedup in problem solving and also uncovers abrupt changes in reaction time, which reflect changes in the cognitive processes that participants are using to solve math problems. We find that as participants practice solving math problems they transition through 3 distinct learning states. Each learning state shows some speedup with practice, but the major speedups are produced by transitions between learning states. In examining and comparing the behavioral and neurological profiles of each of these states, we find parallels with the 3 phases of skill acquisition proposed by Fitts and Posner (1967): a cognitive, an associative, and an autonomous phase. (PsycINFO Database Record PMID- 26551627 TI - When intensions do not map onto extensions: Individual differences in conceptualization. AB - Concepts are represented in the mind through knowledge of their extensions (the class of items to which the concept applies) and intensions (features that distinguish that class of items). A common assumption among theories of concepts is that the 2 aspects are intimately related. Hence if there is systematic individual variation in concept representation, the variation should correlate between extensional and intensional measures. A pair of individuals with similar extensional beliefs about a given concept should also share similar intensional beliefs. To test this notion, exemplars (extensions) and features (intensions) of common categories were rated for typicality and importance respectively across 2 occasions. Within-subject consistency was greater than between-subjects consensus on each task, providing evidence for systematic individual variation. Furthermore, the similarity structure between individuals for each task was stable across occasions. However, across 5 samples, similarity between individuals for extensional judgments did not map onto similarity between individuals for intensional judgments. The results challenge the assumption common to many theories of conceptual representation that intensions determine extensions and support a hybrid view of concepts where there is a disconnection between the conceptual resources that are used for the 2 tasks. PMID- 26551628 TI - Peripheral quantitative computed tomography (pQCT) bone measurements in children with cystic fibrosis. AB - BACKGROUND: Individuals with cystic fibrosis (CF) have low bone density and increased fracture risk. METHODS: Cross-sectional study investigating whole body bone mineral content (WBBMC), bone geometry and strength in 12 children with CF compared to 23 age- and sex-matched controls with and without adjusting for age, height, and body composition. RESULTS: CF group had lower WBBMC than controls (P = 0.007) with larger differences at older ages (age-by-group, P = 0.08). CF group had decreased height (P = 0.006), a trend of lower lean mass per height (P = 0.08), and no difference in relationship between WBBMC and lean mass compared to controls (P = 0.65). Periosteal and endosteal circumferences were smaller in CF (each, P = 0.02). Positive relationships of cortical area and bone strength with age were attenuated with CF (group-by-age; each, P < 0.01). CONCLUSION: Children with CF have similar WBBMC relative to lean mass as controls. Cortical bone area and bone strength were less in CF group compared to controls, with greater differences in older children. PMID- 26551629 TI - Eccrine poroma: correlation of reflectance confocal microscopy and histopathology of horizontal sections. PMID- 26551630 TI - Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma. AB - Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5"-azido neomycin B and its FDA approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics. PMID- 26551631 TI - Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue. AB - The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. On the basis of this crystal structure as well as a wealth of biochemical studies, we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid. PMID- 26551632 TI - The Role of Government in Health Care Reform in the United States and England. PMID- 26551633 TI - Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States. AB - One of the major projects of the Worldwide Network for Blood and Marrow Transplantation (WBMT) is to promote hematopoietic stem cell transplantation (HSCT) in emerging countries in the world. For these countries, HLA haploidentical HSCT (haplo-HSCT) from family members is an attractive approach because of its cost effectiveness. To learn the current status, including recent trends, of haplo-HSCT, the WBMT invited speakers from major transplant centers in 3 regions (Asia, Europe, and North America) to present at its annual WBMT Joint Session. This article represents the direct reports from these 3 speakers in addition to introductions by 2 WBMT speakers who address data from the Global Transplant Activity survey. It must be emphasized, however, that certain promising results of haplo-HSCT presented in this article were obtained at well experienced institutes. PMID- 26551634 TI - Bone Marrow Harvesting of Allogeneic Donors in an Outpatient Setting: A Single Center Experience. AB - The aim of this retrospective study was to assess the safety and efficacy of bone marrow (BM) harvesting of allogeneic donors in an outpatient setting. Data of 226 related and unrelated donors who underwent BM harvest under general anesthesia at our institution from 2002 to 2014 were analyzed. Sixteen patients were a priori planned for admission for social reasons and 210 patients underwent BM harvesting with the intention to perform this procedure on an outpatient basis. To identify factors that predispose for hospital admission, we retrospectively analyzed donor characteristics and collection parameters. Outpatient treatment was performed in 178 of 210 donors (85%), whereas 32 donors (15%) required admission for clinical reasons (mainly clinically relevant anemia and circulatory problems). These individuals were not significantly different in sex distribution, age, donor's body weight, and the proportion of related donors from those who were not admitted. However, we found a significantly higher collection volume per kilogram donor's body weight in inpatients compared with volume for outpatients (16 versus 13 mL/kg body weight, P < .001). Severe adverse events or deaths occurred neither in the inpatient nor in the outpatient setting. Our study demonstrated that BM harvest in an outpatient setting is safe and feasible for the majority of allogeneic donors. A high volume of BM represented a major risk factor for inpatient admission. PMID- 26551635 TI - Myeloablative, but not Reduced-Intensity, Conditioning Overcomes the Negative Effect of Flow-Cytometric Evidence of Leukemia in Acute Myeloid Leukemia. AB - Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS), and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens in 203 patients (MAC, n = 80, and RIC, n = 123) with no morphologic evidence of persistent AML pretransplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pretransplant standard sensitivity FC to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, DFS, and OS (multiple regression HR, 3.8; 95% CI, 1.7 to 8.7; P < .01 for relapse; HR, 2.9; 95% CI, 1.4 to 5.9; P < .01 for DFS; and HR, 3.4; 95% CI, 1.7 to 7; P < .01 for OS). In contrast, FC+ status was not associated with relapse or decreased OS after MAC. These data suggest that MAC, but not RIC, overcomes the negative effect of pretransplant FC+ after sibling or UCB alloHCT. Therefore, a deeper pretransplant leukemia-free state is preferred for those treated with RIC. PMID- 26551636 TI - Combination Therapy for Graft-versus-Host Disease Prophylaxis with Etanercept and Extracorporeal Photopheresis: Results of a Phase II Clinical Trial. AB - Reduced-intensity conditioning (RIC) regimens minimize early toxicity after allogeneic hematopoietic cell transplantation (HCT) by placing greater reliance on establishing a graft-versus-leukemia effect (GVL). Because graft-versus-host disease (GVHD) and GVL are tightly linked, inhibition of T cell populations that cause GVHD may lead to an unintended increased risk of relapse in the RIC setting. Although not completely understood, etanercept and extracorporeal photopheresis (ECP) are thought to ameliorate GVHD without direct T cell inhibition. We hypothesized that adding these 2 agents to a standard GVHD prophylaxis regimen of tacrolimus and mycophenolate mofetil (MMF) would improve survival by reducing GVHD-related mortality without increasing relapse rates. Therefore, we conducted a prospective phase II clinical trial that incorporated tacrolimus, MMF, etanercept, and ECP as GVHD prophylaxis in 48 patients undergoing RIC unrelated donor transplantation. The preferred RIC was fludarabine 160 mg/m(2) + busulfan 6.4 mg/kg to 12.8 mg/kg +/- total body irradiation 200 cGy. Etanercept .4 mg/kg (maximum dose, 25 mg) was given subcutaneously twice weekly for 8 weeks after HCT and ECP was given for 12 treatments, starting weekly on day 28 weekly and tapering off by day 180. The median age of the study patients was 60 (range, 18 to 71) years. Donors were 7/8 (n = 14, 29%) or 8/8 (n = 34, 71%) HLA matched. All patients engrafted neutrophils at a median of 12 days. The cumulative incidence of grades II to IV acute GVHD at day 100 was 46%, but it was typically sensitive to initial steroid treatment (84% day 56 complete response/partial response rate). Overall survival at 1 year in this older, frequently mismatched unrelated donor setting was excellent (73%) because of low rates of nonrelapse mortality (21%) and relapse (19%). However, this strategy was not effective at preventing a high incidence of chronic GVHD and late deaths led to a drop in 2-year survival, declining to 56%, reflecting a high incidence of chronic GVHD. PMID- 26551637 TI - Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD. AB - Allogeneic hematopoietic cell transplantation (alloHCT) as a postremission therapy in patients with FLT3-ITD-positive intermediate-risk acute myeloid leukemia (AML) remains controversial. FLT3-ITD mutations are heterogeneous with respect to allelic ratio, location, and length of the insertion, with a high mutant-to-wild-type ratio consistently associated with inferior prognosis. We retrospectively analyzed the role of alloHCT in first remission in relationship to the allelic ratio and presence or absence of nucleophosmin 1 mutations (NPM1) in the Study Alliance Leukemia AML2003 trial. FLT3-ITD mutations were detected in 209 patients and concomitant NPM1 mutations in 148 patients. Applying a predefined cutoff ratio of .8, AML was grouped into high- and low-ratio FLT3-ITD AML (HR(FLT3-ITD) and LR(FLT3-ITD)). Sixty-one patients (29%) were transplanted in first remission. Overall survival (OS) (HR, .3; 95% CI, .16 to .7; P = .004) and event-free survival (EFS) (HR, .4; 95% CI, .16 to .9; P = .02) were significantly increased in patients with HR(FLT3-ITD) AML who received alloHCT as consolidation treatment compared with patients who received consolidation chemotherapy. Patients with LR(FLT3-ITD) AML and wild-type NPM1 who received alloHCT in first remission had increased OS (HR, .3; 95% CI, .1 to .8; P = .02) and EFS (HR, .2; 95% CI, .1 to .8; P = .02), whereas alloHCT in first remission did not have a significant impact on OS and EFS in patients with LR(FLT3-ITD) AML and concomitant NPM1 mutation. In conclusion, our results provide additional evidence that alloHCT in first remission improves EFS and OS in patients with HR(FLT3-ITD) AML and in patients with LR(FLT3-ITD) AML and wild-type NPM1. PMID- 26551638 TI - Clinical Findings and Provision of Care in Haemodialysis Patients with Chronic Itch: New Results from the German Epidemiological Haemodialysis Itch Study. AB - The German Epidemiological Haemodialysis Itch Study (GEHIS) has shown that more than one-third of haemodialysis (HD) patients have chronic itch (CI). As part of GEHIS, 216 patients with current CI were offered a dermatological examination, of whom 177 were investigated. According to the clinical classification of the International Forum for the Study of Itch (IFSI), 43.5% (n = 77) of the patients examined had CI with no skin lesions (IFSI II), 37.9% (n = 67) had secondary scratch lesions (IFSI III), and 18.6% (n = 33) primarily had diseased skin (IFSI I). Severity of CI and itch-related quality of life (ItchyQoL) showed a significant association only with IFSI III. Of the patients in this study, 89.8% (n = 159) had xerosis cutis. Only 40.4% (n = 80) had ever sought medical help for CI, 46.4% (n = 32) of whom were in the category IFSI III. Only 32.4% (n = 77) had ever received any treatment for CI and [AQ1] these patients had significantly more severe CI. The current analyses demonstrate that CI is a frequently disregarded symptom in HD patients. PMID- 26551639 TI - Microvascular Disease After Renal Transplantation. AB - BACKGROUND/AIMS: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5. METHODS: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson's modification of the Parr-Hubbard formula. RESULTS: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 +/- 7.5 um and 137.9 +/- 14.9 um, p=0.12; and 199.1 +/- 17.8 um and 202.4 +/- 27.8 um, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively). CONCLUSIONS: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post-transplantation. PMID- 26551640 TI - Informal carers: if we don't know, how can we help? PMID- 26551641 TI - Informal carers and wound management: an integrative literature review. AB - OBJECTIVE: The consequences of informal care giving have been well documented in recent decades, and in many fields of illness and chronic disease, the role of informal carers has been recognised and investigated. Informal caregivers in the field of wound management and prevention have been largely unnoticed, despite the chronic nature of many wounds, the enduring nature of treatments and the impact on the physical and social environment; factors likely to have a significant impact on family and friends. The aim of this study was to consider what published evidence is available regarding the experience and role of informal caregivers in wound management or prevention. METHOD: An integrated literature review was completed in October 2014 searching ESBCOhost database, Wound Management Association websites, and reviewing reference lists of accessed papers. RESULTS: A number of challenges were noted in accessing information about informal carers in relation to wound management and prevention. Most of these arose from the scarcity of studies for which informal carers was the primary focus. The available evidence suggests that informal carers have a role in wound management and prevention and that their involvement is likely to represent a noteworthy economic contribution to the wound management health-care team. Wound management was also determined to yield physical and psychological impacts for the carer. There was limited evidence of structured information, support or training for informal carers, which was flagged by carers as an area of need. CONCLUSION: General conclusions about the burdensome experience and the valuable role of carers were the main interpretations possible from the evidence. More research which purposively and comprehensively examines the experience and role of informal caregivers is required. This knowledge would provide a foundation upon which interventions and support for informal carers and patients can be generated, which could further serve to enhance wound healing and the prevention of skin damage. PMID- 26551642 TI - Slough and biofilm: removal of barriers to wound healing by desloughing. AB - The presence of non-viable tissue in a chronic wound presents a barrier against effective wound healing, hence removal facilitates healing and reduces areas where microorganisms can attach and form biofilms, effectively reducing the risk of infection. Wound debridement is a necessary process in those wounds that have evidence of cellular debris and non-viable tissue. As slough is a form of non viable tissue we hypothesise that it will support the attachment and development of biofilms. Biofilms are entities that have serious implications in raising the risk of infection and delaying wound healing. In those wounds that contain only slough, high-risk debridement methods are not considered necessary for its removal. The use of mechanical techniques for removing the slough is regarded as posing a much lower risk to the patient and the wound bed. The process of removing slough from a wound is referred to as 'desloughing'. We propose that mechanical desloughing is a low-risk method of debridement to aid the specific removal of slough. Slough in a wound is a recurrent issue for a large majority of patients. Consequently, desloughing should not be deemed a one-off process but an on-going procedure referred to as 'maintenance desloughing'. Maintenance desloughing will help to achieve and maintain a healthy wound bed and aid the removal of wound biofilms, facilitating wound healing. PMID- 26551643 TI - Investigating the pressure-reducing effect of wound dressings. AB - OBJECTIVE: Currently, polyurethane foam dressings are commercially available from many manufacturers. However, the pressure-reducing effect is expected to differ by the formulation and combination of the main and secondary ingredients and by manufacturing method. In this study, we investigated the effects of pressure reduction using dressing materials with various structural characteristics, including polyurethane foam dressings based on the engineering point of view, focusing on the dry state. METHOD: Pressure was measured in a model that simulated compression on the sacral region in a decubitus position. Pressure was measured for different dressings: ten products, consisting of five types of material (polyurethane foam, hydropolymeric, Hydrofiber, hydrocolloid, and low adherent absorbent). RESULTS: All dressings used in this study showed significantly reduced pressure. ALLEVYN Non-Adhesive had the lowest pressure at 35.833 +/- 1.155 mmHg, and DuoDERM Extra Thin CGF had the highest pressure at 66.867 +/- 1.060 mmHg. The pressure of the control was 74.667 +/- 1.405 mmHg. The other dressings were: ALLEVYN Adhesive: 44.233 +/- 0.777 mmHg; ALLEVYN Gentle Border: 46.967 +/- 1.537mmHg; Mepilex Border: 53.867 +/- 0.231 mmHg; Biatain Silicone: 56.000 +/- 0.520 mmHg; TIELLE: 57.267 +/- 3.403 mmHg;Versiva XC: 65.900 +/- 0.800 mmHg; DuoDERM CGF: 57.267 +/- 1.007 mmHg; and Melolin: 53.433 +/- 1.973 mmHg. CONCLUSION: The pressure-reducing effect of dressing differs not only by material type but also by product. That is, the pressure-reducing effect can differ even if the dressings are of the same material type, such as polyurethane foam. Our study investigated only the effect of materials and structural characteristics on the cushion of dressings in the dry state. Therefore, further investigation is needed to confirm the effect of pressure reduction by dressing to meet the conditions in the clinic. PMID- 26551644 TI - Measurement of diabetic wounds with optical coherence tomography-based air-jet indentation system and a material testing system. AB - OBJECTIVE: Material testing system is a conventional but destructive method for measuring the biomechanical properties of wound tissues in basic research. The recently developed optical coherence tomography-based air-jet indentation system is a non-destructive method for measuring these properties of soft tissues in a non-contact manner. The aim of the study was to examine the correlation between the biomechanical properties of wound tissues measured by the two systems. METHOD: Young male Sprague-Dawley rats with streptozotocin-induced diabetic were wounded by a 6 mm biopsy punch on their hind limbs. The biomechanical properties of wound tissues were assessed with the two systems on post-wounding days 3, 7, 10, 14, and 21. Wound sections were stained with picro-sirius red for analysis on the collagen fibres. Data obtained on the different days were charted to obtain the change in biomechanical properties across the time points, and then pooled to examine the correlation between measurements made by the two devices. Qualitative analysis to determine any correlation between indentation stiffness measured by the air-jet indentation system and the orientation of collagen fibres. RESULTS: The indentation stiffness is significantly negatively correlated to the maximum load, maximum tensile stress, and Young's modulus by the material testing system (all p<0.05). The orientation of collagen changes with the indentation stiffness over time. CONCLUSION: Our findings support the use of optical coherence tomography-based air-jet indentation system to evaluate the biomechanical properties of wounds in a non-contact manner. It is a potential clinical device to examine the biomechanical properties of chronic wounds in vivo in a repeatable manner. PMID- 26551645 TI - Dehydrated human amnion/chorion membrane treatment of venous leg ulcers: correlation between 4-week and 24-week outcomes. AB - OBJECTIVE: To evaluate correct correlation between an intermediate rate of wound reduction (40% wound area reduction after 4-weeks treatment) and complete healing at 24 weeks in patients with a venous leg ulcer (VLU). METHOD: A retrospective follow-up study of patients completing a multicenter randomised controlled trial (RCT) comparing the number of patients achieving at least 40% healing of their VLU within 4-weeks of treatment with either dehydrated human amnion/chorion membrane (dHACM) allograft or multilayer compression only was conducted. Outcomes assessed were rates of complete healing within 24 weeks of enrolment and days to healing. Data were divided into two groups based on status at RCT completion (healed at least 40% yes or no). Correct correlation with status at 4 weeks and complete healing within 24 weeks was determined. Clinical characteristics were also compared for patients with and without correct correlation between 4-week and 24-week status. RESULTS: We identified 55 patients at 5 study sites. Some 47 without complete healing during the initial study were eligible. As three patients were lost to follow-up we evaluated 44 records. Of these, 20 (45.4%) had reduced wound size of >=40% and 24 (55%) had <40% reduction during the initial study. Complete healing occurred in 16/20 (80%) of the >=40% group at a mean of 46 days, p=0.0027 and 8/24 (33.3%) of the <40% group at a mean of 103.6 days, p=0.0023. Overall, correct correlation of status at 4 weeks and ultimate healing status of VLU occurred in 32/44 patients (73%). CONCLUSION: These results confirm that the intermediate outcome used in our initial study is a viable predictor of ultimate VLU healing. PMID- 26551646 TI - What is the ideal interval between dressing changes during negative pressure wound therapy for open traumatic fractures? AB - OBJECTIVE: Negative pressure wound therapy (NPWT) is effective in infection control during treatment of severe open fractures. However frequent dressing changes during NPWT are costly and cause patient discomfort. If the interval between dressing changes could be extended, these problems would be reduced. In this article we compare the outcomes of open IIIB fractures with 3-day versus 7 day intervals between dressing changes. METHOD: Patients who sustained Gustilo IIIB open fractures were included. All underwent conventional orthopaedic fixation with delayed latissimus dorsi flap coverage. Group 1 had 3-day intervals between dressing changes and group 2 had 7-day intervals. The final outcomes in the two groups were analysed. RESULTS: There were 38 patients in group 1 and 34 patients in group 2. Although the period between admission and final operation was similar in the two groups, the mean number of NPWT changes was 4.54 in 3 day in group 1 and 1.95 in group 2 (p<0.001). This led to a difference in NPWT related costs; $341.26 in group 1 and $237.49 in group 2 (p<0.001). There was no difference in the frequency of complications such as infection or non-union of fractures. CONCLUSION: NPWT is useful treatment option for open fractures, to bridge between initial debridement and final microsurgical tissue transfer. Considering patient comfort, the costs related to the NPWT, and the final flap results, a 7-day interval between changes of the NPWT is acceptable. PMID- 26551647 TI - The use of a collagen matrix in hard-to-heal venous leg ulcers. AB - OBJECTIVE: The effects of a collagen dressing on hard-to-heal venous leg ulcers (vlUs) were evaluated in this prospective, randomised, controlled study. METHOD: Patients with hard-to-heal vlU were included and divided into two groups using the block randomisation method. The first group was treated with a collagen and an alginate dressing (group A), and the second group with an alginate dressing alone (group b). both groups also had a short-stretch compression system applied at every dressing change. The dressings were changed twice a week for 12 weeks or until the ulcer was healed. Granulation tissue improvement, wound size, overall dressing performance and dressing comfort were evaluated and recorded. RESULTS: A total of 40 patients completed the study evaluation period. Group A had a 65% increase in granulation tissue compared to 38% in group b. The mean ulcer area was reduced to 45% in group A compared to 20% in group b at 12 weeks. no significant side effects were detected in either group. Patients of both groups were satisfied with their treatment and healing progress. CONCLUSION: The results of this study showed the effectiveness and safety of a collagen dressing in hard to-heal vlUs as an adjunctive therapy with compression bandaging. These encouraging results may positively affect the quality of life of patients with chronic wounds. PMID- 26551648 TI - Children with Autism Understand Indirect Speech Acts: Evidence from a Semi Structured Act-Out Task. AB - Children with Autism Spectrum Disorder are often said to present a global pragmatic impairment. However, there is some observational evidence that context based comprehension of indirect requests may be preserved in autism. In order to provide experimental confirmation to this hypothesis, indirect speech act comprehension was tested in a group of 15 children with autism between 7 and 12 years and a group of 20 typically developing children between 2:7 and 3:6 years. The aim of the study was to determine whether children with autism can display genuinely contextual understanding of indirect requests. The experiment consisted of a three-pronged semi-structured task involving Mr Potato Head. In the first phase a declarative sentence was uttered by one adult as an instruction to put a garment on a Mr Potato Head toy; in the second the same sentence was uttered as a comment on a picture by another speaker; in the third phase the same sentence was uttered as a comment on a picture by the first speaker. Children with autism complied with the indirect request in the first phase and demonstrated the capacity to inhibit the directive interpretation in phases 2 and 3. TD children had some difficulty in understanding the indirect instruction in phase 1. These results call for a more nuanced view of pragmatic dysfunction in autism. PMID- 26551649 TI - Game Theoretical Analysis on Cooperation Stability and Incentive Effectiveness in Community Networks. AB - Community networks, the distinguishing feature of which is membership admittance, appear on P2P networks, social networks, and conventional Web networks. Joining the network costs money, time or network bandwidth, but the individuals get access to special resources owned by the community in return. The prosperity and stability of the community are determined by both the policy of admittance and the attraction of the privileges gained by joining. However, some misbehaving users can get the dedicated resources with some illicit and low-cost approaches, which introduce instability into the community, a phenomenon that will destroy the membership policy. In this paper, we analyze on the stability using game theory on such a phenomenon. We propose a game-theoretical model of stability analysis in community networks and provide conditions for a stable community. We then extend the model to analyze the effectiveness of different incentive policies, which could be used when the community cannot maintain its members in certain situations. Then we verify those models through a simulation. Finally, we discuss several ways to promote community network's stability by adjusting the network's properties and give some proposal on the designs of these types of networks from the points of game theory and stability. PMID- 26551650 TI - Acidogenic fermentation of Scenedesmus sp.-AMDD: Comparison of volatile fatty acids yields between mesophilic and thermophilic conditions. AB - This study compared the acidogenic fermentation of Scenedesmus sp.-AMDD at laboratory-scale, under mesophilic (35 degrees C) and thermophilic conditions (55 degrees C). Preliminary batch tests were performed to evaluate best conditions for volatile fatty acid (VFA) production from microalgal biomass, with respect to the inoculum, pH and nutrients. The use of bovine manure as inoculum, the operating pH of 4.5 and the addition of a nutrient mix, resulted in a high VFA production of up to 222mgg(-1) total volatile solid (TVS), with a butyrate share of 27%. Both digesters displayed similar hydrolytic activity with 0.38+/-0.02 and 0.42+/-0.03 g soluble chemical oxygen demand (COD)g(-1) TVS for the digesters operated at 35 and 55 degrees C, respectively. Mesophilic conditions were more favorable for VFA production, which reached 171+/-5, compared to 88+/-12 mg soluble CODg(-1) TVS added under thermophilic conditions (94% more). It was shown that in both digesters, butyrate was the predominant VFA. PMID- 26551651 TI - Semi-aerobic fermentation as a novel pre-treatment to obtain VFA and increase methane yield from primary sludge. AB - There is a growing trend to consider organic wastes as potential sources of renewable energy and value-add products. Fermentation products have emerged as attractive value-add option due to relative easy production and broad application range. However, pre-fermentation and extraction of soluble products may impact down-stream treatment processes, particularly energy recovery by anaerobic digestion. This paper investigates primary sludge pre-fermentation at different temperatures (20, 37, 55, and 70 degrees C), treatment times (12, 24, 48, and 72h), and oxygen availability (semi-aerobic, anaerobic); and its impact on anaerobic digestion. Pre-fermentation at 20 and 37 degrees C succeeded for VFA production with acetate and propionate being major products. Pre-fermentation at 37, 55, and 70 degrees C resulted in higher solubilisation yield but it reduced sludge methane potential by 20%. Under semi-aerobic conditions, pre-fermentation allowed both VFA recovery (43gCODVFAkg(-1)VS) and improved methane potential. The latter phenomenon was linked to fungi that colonised the sludge top layer during pre-fermentation. PMID- 26551652 TI - Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept. AB - The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery. PMID- 26551653 TI - Ethanol fermentation integrated with PDMS composite membrane: An effective process. AB - The polydimethylsiloxane (PDMS) membrane, prepared in water phase, was investigated in separation ethanol from model ethanol/water mixture and fermentation-pervaporation integrated process. Results showed that the PDMS membrane could effectively separate ethanol from model solution. When integrated with batch ethanol fermentation, the ethanol productivity was enhanced compared with conventional process. Fed-batch and continuous ethanol fermentation with pervaporation were also performed and studied. 396.2-663.7g/m(2)h and 332.4 548.1g/m(2)h of total flux with separation factor of 8.6-11.7 and 8-11.6, were generated in the fed-batch and continuous fermentation with pervaporation scenario, respectively. At the same time, high titre ethanol production of ~417.2g/L and ~446.3g/L were also achieved on the permeate side of membrane in the two scenarios, respectively. The integrated process was environmental friendly and energy saving, and has a promising perspective in long-terms operation. PMID- 26551654 TI - Estimation of beech pyrolysis kinetic parameters by Shuffled Complex Evolution. AB - The pyrolysis kinetics of a typical biomass energy feedstock, beech, was investigated based on thermogravimetric analysis over a wide heating rate range from 5K/min to 80K/min. A three-component (corresponding to hemicellulose, cellulose and lignin) parallel decomposition reaction scheme was applied to describe the experimental data. The resulting kinetic reaction model was coupled to an evolutionary optimization algorithm (Shuffled Complex Evolution, SCE) to obtain model parameters. To the authors' knowledge, this is the first study in which SCE has been used in the context of thermogravimetry. The kinetic parameters were simultaneously optimized against data for 10, 20 and 60K/min heating rates, providing excellent fits to experimental data. Furthermore, it was shown that the optimized parameters were applicable to heating rates (5 and 80K/min) beyond those used to generate them. Finally, the predicted results based on optimized parameters were contrasted with those based on the literature. PMID- 26551655 TI - Assessing the Patient Care Implications of "Concierge" and Other Direct Patient Contracting Practices: A Policy Position Paper From the American College of Physicians. AB - As physicians seek innovative practice models, one that is gaining ground is for practices to contract with patients to pay directly for some or all services often called cash-only, retainer, boutique, concierge, or direct primary care or specialty care practices. Such descriptions do not reflect the variability found in practices. For the purposes of this paper, the American College of Physicians (ACP) defines a direct patient contracting practice (DPCP) as any practice that directly contracts with patients to pay out-of-pocket for some or all of the services provided by the practice, in lieu of or in addition to traditional insurance arrangements, and/or charges an administrative fee to patients, sometimes called a retainer or concierge fee, often in return for a promise of more personalized and accessible care. This definition encompasses the practice types previously described. The move to DPCPs is based on the premise that access and quality of care will be improved without third-party payers imposing themselves between the patient and the physician. Yet concerns have been raised that DPCPs may cause access issues for patients who cannot afford to pay directly for care. This ACP position paper, initiated and written by its Medical Practice and Quality Committee and approved by the Board of Regents on 25 July 2015, assesses the impact of DPCPs on access, cost, and quality; discusses principles from the ACP Ethics Manual, Sixth Edition, that should apply to all practice types; and makes recommendations to mitigate any adverse effect on underserved patients. PMID- 26551656 TI - Democratic parenting beliefs and observed parental sensitivity: Reciprocal influences between coparents. AB - Three hundred sixty-five 2-parent families from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development were rated by trained observers on their parenting behavior at 6 assessments ranging from 6 months after the child's birth to when the child was in fifth grade (M = 10.4 years old at fifth grade). Across assessments, parents reported on their parenting beliefs and mothers reported on the child's externalizing behavior problems. Parenting beliefs predicted change in parenting behavior, and to a lesser degree parenting behavior predicted change in parenting beliefs. Parenting behavior and parenting beliefs both showed reciprocal effects between coparents, after controlling for child externalizing behavior and parent education. (PsycINFO Database Record PMID- 26551657 TI - The influence of family unions and parenthood transitions on self-development. AB - The present study discusses the impact of union and parenthood transitions on individuals' self-esteem and sense of mastery development from midadolescence to young adulthood by using multilevel analyses with longitudinal data of 7,339 individuals between ages 15 and 38. The results show that, first, individuals in marital unions show significantly greater rates of growth in self-esteem and sense of mastery, compared with singles. Therefore, entering into marriage provides greater protections to individuals' self-esteem and sense of mastery. Second, the transition to parenthood brings significant decreases in levels and increases in rates of change in self-esteem and sense of mastery among new parents. The degree of the aforementioned changes differs by new parents' gender, union status, and living arrangement with the child at childbirth. Women are influenced more negatively than men. Living with the child at childbirth reduces the degree of decreases in self-esteem and sense of mastery, especially for mothers. In sum, from midadolescence to young adulthood, the development of individuals' self-esteem and sense of mastery is shaped by their union and parenthood transitions. Moreover, the context where these transitions take place, including the type of union and the living arrangement, moderates the degree of the impact. Our findings have important implications for research and practice in promoting the family transition experience. PMID- 26551658 TI - Effects of economic hardship: Testing the family stress model over time. AB - The current study evaluated connections between marital distress, harsh parenting, and child externalizing behaviors in line with predictions from the Family Stress Model (FSM). Prospective, longitudinal data came from 273 mothers, fathers, and children participating when the child was 2, between 3 and 5, and between 6 and 10 years old. Assessments included observational and self-report measures. Information regarding economic hardship and economic pressure were assessed during toddlerhood, and parental emotional distress, couple conflict, and harsh parenting were collected during early childhood. Child externalizing behavior was assessed during both toddlerhood and middle childhood. Results were consistent with predictions from the FSM in that economic hardship led to economic pressure, which was associated with parental emotional distress and couple conflict. This conflict was associated with harsh parenting and child problem behavior. This pathway remained statistically significant controlling for externalizing behavior in toddlerhood. PMID- 26551659 TI - A longitudinal examination of positive parenting following an acceptance-based couple intervention. AB - Positive parenting practices have been shown to be essential for healthy child development, and yet have also been found to be particularly challenging for parents to enact and maintain. This article explores an innovative approach for increasing positive parenting by targeting specific positive emotional processes within marital relationships. Couple emotional acceptance is a powerful mechanism that has repeatedly been found to improve romantic relationships, but whether these effects extend to the larger family environment is less well understood. The current longitudinal study examined the impact of improved relational acceptance after a couple intervention on mother's and father's positive parenting. Participants included 244 parents (122 couples) in the Marriage Checkup (MC) study, a randomized, controlled, acceptance-based, intervention study. Data indicated that both women and men experienced significantly greater felt acceptance 2 weeks after the MC intervention, treatment women demonstrated greater positive parenting 2 weeks after the intervention, and all treatment participants' positive parenting was better maintained than control couple's 6 months later. Importantly, although mothers' positive parenting was not influenced by different levels of felt acceptance, changes in father's positive parenting were positively associated with changes in felt acceptance. As men felt more accepted by their wives, their levels of positive parenting changed in kind, and this effect on positive parenting was found to be mediated by felt acceptance 2 weeks after the MC. Overall, findings supported the potential benefits of targeting couple acceptance to generate positive cascades throughout the larger family system. PMID- 26551660 TI - Emergence of novel nephropathogenic infectious bronchitis viruses currently circulating in Chinese chicken flocks. AB - The emergence of novel infectious bronchitis viruses (IBVs) has been reported worldwide. Between 2011 and 2014, eight IBV isolates were identified from disease outbreaks in northeast China. In the current study we analysed the S1 gene of these eight IBV isolates in addition to the complete genome of five of them. We confirmed that these isolates emerged through the recombination of LX4 and Taiwan group 1 (TW1) viruses at two switch sites, one was in the Nsp 16 region and the other in the spike protein gene. The S1 gene in these viruses exhibited high nucleotide similarity with TW1-like viruses; the TW1 genotype was found to be present in southern China from 2009. Pathogenicity experiments in chickens using three of the eight virus isolates revealed that they were nephropathogenic and had similar pathogenicity to the parental viruses. The results of our study demonstrate that recombination, coupled with mutations, is responsible for the emergence of novel IBVs. PMID- 26551661 TI - Emotional face processing in post-traumatic stress disorder after reconsolidation impairment using propranolol: A pilot fMRI study. AB - Individuals with post-traumatic stress disorder (PTSD) exhibit exaggerated emotional reactions to threatening stimuli, which may represent deregulated fear conditioning, associated with long-term adaptations in the sympathetic nervous system. Within a repeated measures design, functional magnetic resonance imaging (fMRI) was employed to investigate neural responses to threat in PTSD participants (N=7), during the presentation of emotional facial expressions. Scans were separated by 6 weekly reconsolidation impairment treatment sessions, consisting of traumatic memory reactivation under the influence of propranolol. Greater activation before versus after treatment emerged in the thalamus and amygdala during fearful versus neutral face processing. Furthermore, participants showed greater activation after versus before treatment in the right anterior cingulate, during fearful relative to happy face processing. PTSD symptoms significantly improved (d=1.75), post-treatment. These preliminary results suggest that aberrant emotional responding is modulated by noradrenergic plasticity within the amygdala-prefrontal cortex circuit, a neural substrate for the pharmacological treatment of PTSD. PMID- 26551662 TI - Treatment of sulfonylurea and insulin overdose. AB - The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l(-1) . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide. PMID- 26551663 TI - Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins. AB - BACKGROUND: Many observational studies have shown a protective effect of physical activity on cognitive ageing, but interventional studies have been less convincing. This may be due to short time scales of interventions, suboptimal interventional regimes or lack of lasting effect. Confounding through common genetic and developmental causes is also possible. OBJECTIVES: We aimed to test whether muscle fitness (measured by leg power) could predict cognitive change in a healthy older population over a 10-year time interval, how this performed alongside other predictors of cognitive ageing, and whether this effect was confounded by factors shared by twins. In addition, we investigated whether differences in leg power were predictive of differences in brain structure and function after 12 years of follow-up in identical twin pairs. METHODS: A total of 324 healthy female twins (average age at baseline 55, range 43-73) performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) at two time points 10 years apart. Linear regression modelling was used to assess the relationships between baseline leg power, physical activity and subsequent cognitive change, adjusting comprehensively for baseline covariates (including heart disease, diabetes, blood pressure, fasting blood glucose, lipids, diet, body habitus, smoking and alcohol habits, reading IQ, socioeconomic status and birthweight). A discordant twin approach was used to adjust for factors shared by twins. A subset of monozygotic pairs then underwent magnetic resonance imaging. The relationship between muscle fitness and brain structure and function was assessed using linear regression modelling and paired t tests. RESULTS: A striking protective relationship was found between muscle fitness (leg power) and both 10-year cognitive change [fully adjusted model standardised beta-coefficient (Stdbeta) = 0.174, p = 0.002] and subsequent total grey matter (Stdbeta = 0.362, p = 0.005). These effects were robust in discordant twin analyses, where within-pair difference in physical fitness was also predictive of within-pair difference in lateral ventricle size. There was a weak independent effect of self-reported physical activity. CONCLUSION: Leg power predicts both cognitive ageing and global brain structure, despite controlling for common genetics and early life environment shared by twins. Interventions targeted to improve leg power in the long term may help reach a universal goal of healthy cognitive ageing. PMID- 26551664 TI - Host-guest complexation of di-cyclohexanocucurbit[6]uril and hexa cyclohexanocucurbit[6]uril with alkyldiammonium ions: a comparative study. AB - The host-guest complexation of symmetrical di-cyclohexanocucurbit[6]uril (Cy2Q[6]) and hexa-cyclohexanocucurbit[6]uril (Cy6Q[6]) with a series of alkyldiammonium ions (H(3+)N(CH(2))nNH(3+), n = 2-8) has been studied both in solution and in the gas phase. (1)H NMR data indicate that all alkyldiammonium ions have inclusion interactions with both hosts except for the ethanediammonium ion. In addition, if the alkyl chain of the alkyldiammonium ion is longer than n = 5 methylene groups, compressed conformation may occur, which depends on the cavity shape of the hosts and the length of the alkyl chain. Isothermal titration calorimetry (ITC) studies point out that the host-guest complexations of both hosts with the latter five alkyldiammonium ions are enthalpically driven. The comparison of the thermodynamic data reveals that the enthalpies of the van der Waals interactions contribute more to the host-guest complexation enthalpy than the ion-dipole interactions. The enthalpic gain arises from the van der Waals interactions and the reduction of entropy upon the host-guest complexation is strongly affected by the cavity shape of the host. Gas phase structures of long alkyldiammonium guests within both hosts are completely different from those in aqueous solution. PMID- 26551665 TI - Versatile Soft Grippers with Intrinsic Electroadhesion Based on Multifunctional Polymer Actuators. AB - A highly versatile soft gripper that can handle an unprecedented range of object types is developed based on a new design of dielectric elastomer actuators employing an interdigitated electrode geometry, simultaneously maximizing both electroadhesion and electrostatic actuation while incorporating self-sensing. The multifunctionality of the actuator leads to a highly integrated, lightweight, fast, soft gripper with simplified structure and control. PMID- 26551666 TI - Achilles' Lead: Will Pacemakers Break Free? PMID- 26551667 TI - The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome. AB - Sezary syndrome is a leukemic and aggressive form of cutaneous T cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4(+) T cells. Here we performed whole-exome sequencing of tumor-normal sample pairs from 25 patients with Sezary syndrome and 17 patients with other CTCLs. These analyses identified a distinctive pattern of somatic copy number alterations in Sezary syndrome, including highly prevalent chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A and CDKN1B tumor suppressors. Mutation analysis identified a broad spectrum of somatic mutations in key genes involved in epigenetic regulation (TET2, CREBBP, KMT2D (MLL2), KMT2C (MLL3), BRD9, SMARCA4 and CHD3) and signaling, including MAPK1, BRAF, CARD11 and PRKG1 mutations driving increased MAPK, NF-kappaB and NFAT activity upon T cell receptor stimulation. Collectively, our findings provide new insights into the genetics of Sezary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases. PMID- 26551668 TI - Mutations in the transcriptional repressor REST predispose to Wilms tumor. AB - Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1 silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development. Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for ~2% of Wilms tumor. PMID- 26551669 TI - Clock-like mutational processes in human somatic cells. AB - During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operating in human somatic cells. PMID- 26551670 TI - Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. AB - Sezary syndrome is a rare leukemic form of cutaneous T cell lymphoma characterized by generalized redness, scaling, itching and increased numbers of circulating atypical T lymphocytes. It is rarely curable, with poor prognosis. Here we present a multiplatform genomic analysis of 37 patients with Sezary syndrome that implicates dysregulation of cell cycle checkpoint and T cell signaling. Frequent somatic alterations were identified in TP53, CARD11, CCR4, PLCG1, CDKN2A, ARID1A, RPS6KA1 and ZEB1. Activating CCR4 and CARD11 mutations were detected in nearly one-third of patients. ZEB1, encoding a transcription repressor essential for T cell differentiation, was deleted in over one-half of patients. IL32 and IL2RG were overexpressed in nearly all cases. Our results demonstrate profound disruption of key signaling pathways in Sezary syndrome and suggest potential targets for new therapies. PMID- 26551671 TI - A recently evolved hexose transporter variant confers resistance to multiple pathogens in wheat. AB - As there are numerous pathogen species that cause disease and limit yields of crops, such as wheat (Triticum aestivum), single genes that provide resistance to multiple pathogens are valuable in crop improvement. The mechanistic basis of multi-pathogen resistance is largely unknown. Here we use comparative genomics, mutagenesis and transformation to isolate the wheat Lr67 gene, which confers partial resistance to all three wheat rust pathogen species and powdery mildew. The Lr67 resistance gene encodes a predicted hexose transporter (LR67res) that differs from the susceptible form of the same protein (LR67sus) by two amino acids that are conserved in orthologous hexose transporters. Sugar uptake assays show that LR67sus, and related proteins encoded by homeoalleles, function as high affinity glucose transporters. LR67res exerts a dominant-negative effect through heterodimerization with these functional transporters to reduce glucose uptake. Alterations in hexose transport in infected leaves may explain its ability to reduce the growth of multiple biotrophic pathogen species. PMID- 26551673 TI - An investigation into the usefulness of different empirical modeling techniques for better control of spray-on fluidized bed melt granulation. AB - Melt granulation in fluid bed processors is an emerging technique, but literature data regarding the modeling of this granulation method are lacking. In the present study different techniques (response surface analysis, multilayer perceptron neural network, and partial least squares method) were applied for modeling of spray-on fluidized bed melt granulation. Experiments were organized in line with central composite design. The effect of binder content and spray air pressure on granule properties was evaluated. The results obtained indicate that binder content can be identified as a critical factor controlling the granule size and size distribution. It was found that agglomeration mechanism involved, i.e., granule shape, can be greatly influenced by binder properties. The spray air pressure was identified as critical process parameter affecting granule flowability. The results presented indicate that application of in silico tools enables enhanced understanding and better control of novel pharmaceutical processes, such as melt granulation in fluidized bed. The artificial neural networks and partial least squares method were found to be superior to response surface methodology in prediction of granule properties. According to the results obtained, application of more advanced empirical modeling techniques complementary to design of experiments can be a suitable approach in defining the design space and optimization of spray-on fluidized bed melt granulation. PMID- 26551674 TI - An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms. AB - Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit((r)) L30 D-55, Eudragit((r)) EPO, Opadry((r)) AMB and Sepifilm((r)) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25 degrees C). Accelerated stability studies were undertaken at 75% RH/25 degrees C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit((r)) L30 D 55), 0.35% (Opadry((r)) AMB), 0.49% (Sepifilm((r)) LP) and 0.76% (Eudragit((r)) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit(r) L30 D-55 coated cores 78.8%; Opadry((r)) AMB coated cores 76.2%, Sepifilm((r)) LP coated cores 76.0% and Eudragit((r)) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms. PMID- 26551675 TI - In situ polyethylene sebacate particulate carriers as an alternative to Freund's adjuvant for delivery of a contraceptive peptide vaccine--A feasibility study. AB - The present study evaluates the feasibility of particulate carriers of a biodegradable polymer polyethylene sebacate (PES) as an alternative to Freund's adjuvant in the design of a peptide vaccine formulation. The vaccine formulation comprised of PES and the antigen KLH conjugated 80kDa HSA peptide-1 dissolved in N-methyl-2-pyrrolidone (NMP)/NMP-water as solvent. The antigen revealed good stability and the formulations were readily syringeable. Intradermal injection of the formulations resulted in the formation of PES particulates in situ at the site of injection. The NMP formulations revealed larger particulates which elicited no immunogenic response when injected in rabbits. On the other hand the NMP-water formulation revealed formation of microparticles which were significantly smaller in size, in combination with a small fraction of nanoparticles. It elicited an antibody titer up to 1:3200 in rabbits following intradermal injection. Western blot confirmed generation of antibodies specific to the peptide. Contraceptive efficacy was confirmed by loss of sperm motility and head-to-head agglutination of sperms in the treatment group. Unlike the severe reactions observed with administration of Freund's adjuvant, only mild hypersensitivity reaction was observed with the PES formulations. The mild reaction coupled with the contraceptive efficacy observed suggested PES particulates as a viable alternative to Freund's adjuvant. PMID- 26551676 TI - Dynamic metabolic flux analysis using a convex analysis approach: Application to hybridoma cell cultures in perfusion. AB - In recent years, dynamic metabolic flux analysis (DMFA) has been developed in order to evaluate the dynamic evolution of the metabolic fluxes. Most of the proposed approaches are dedicated to exactly determined or overdetermined systems. When an underdetermined system is considered, the literature suggests the use of dynamic flux balance analysis (DFBA). However the main challenge of this approach is to determine an appropriate objective function, which remains valid over the whole culture. In this work, we propose an alternative dynamic metabolic flux analysis based on convex analysis, DMFCA, which allows the determination of bounded intervals for the fluxes using the available knowledge of the metabolic network and information provided by the time evolution of extracellular component concentrations. Smoothing splines and mass balance differential equations are used to estimate the time evolution of the uptake and excretion rates from this experimental data. The main advantage of the proposed procedure is that it does not require additional constraints or objective functions, and provides relatively narrow intervals for the intracellular metabolic fluxes. DMFCA is applied to experimental data from hybridoma HB58 cell perfusion cultures, in order to investigate the influence of the operating mode (batch and perfusion) on the metabolic flux distribution. PMID- 26551677 TI - Ebola viral load at diagnosis associates with patient outcome and outbreak evolution. AB - BACKGROUND: Ebola virus (EBOV) causes periodic outbreaks of life-threatening EBOV disease in Africa. Historically, these outbreaks have been relatively small and geographically contained; however, the magnitude of the EBOV outbreak that began in 2014 in West Africa has been unprecedented. The aim of this study was to describe the viral kinetics of EBOV during this outbreak and identify factors that contribute to outbreak progression. METHODS: From July to December 2014, one laboratory in Sierra Leone processed over 2,700 patient samples for EBOV detection by quantitative PCR (qPCR). Viremia was measured following patient admission. Age, sex, and approximate time of symptom onset were also recorded for each patient. The data was analyzed using various mathematical models to find trends of potential interest. RESULTS: The analysis revealed a significant difference (P = 2.7 * 10(-77)) between the initial viremia of survivors (4.02 log10 genome equivalents [GEQ]/ml) and nonsurvivors (6.18 log10 GEQ/ml). At the population level, patient viral loads were higher on average in July than in November, even when accounting for outcome and time since onset of symptoms. This decrease in viral loads temporally correlated with an increase in circulating EBOV-specific IgG antibodies among individuals who were suspected of being infected but shown to be negative for the virus by PCR. CONCLUSIONS: Our results indicate that initial viremia is associated with outcome of the individual and outbreak duration; therefore, care must be taken in planning clinical trials and interventions. Additional research in virus adaptation and the impacts of host factors on EBOV transmission and pathogenesis is needed. PMID- 26551678 TI - Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. AB - Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM. PMID- 26551679 TI - Coordinate expression of heme and globin is essential for effective erythropoiesis. AB - Erythropoiesis requires rapid and extensive hemoglobin production. Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a potent inducer of oxidative damage, its levels within cellular compartments require stringent regulation. Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear. Here, we determined that erythropoiesis failure occurs in these animals at the CFU E/proerythroblast stage, a point at which the transferrin receptor (CD71) is upregulated, iron is imported, and heme is synthesized--before ample globin is produced. From the CFU-E/proerythroblast (CD71(+) Ter119(-) cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119(-) erythroid cells when studying erythroid marrow failure in murine models. PMID- 26551680 TI - Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV infected macaques. AB - Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection. PMID- 26551681 TI - Platelet-derived HMGB1 is a critical mediator of thrombosis. AB - Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation. PMID- 26551682 TI - Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors. AB - The incidence of cancer is higher in the elderly; however, many of the underlying mechanisms for this association remain unexplored. Here, we have shown that B cell progenitors in old mice exhibit marked signaling, gene expression, and metabolic defects. Moreover, B cell progenitors that developed from hematopoietic stem cells (HSCs) transferred from young mice into aged animals exhibited similar fitness defects. We further demonstrated that ectopic expression of the oncogenes BCR-ABL, NRAS(V12), or Myc restored B cell progenitor fitness, leading to selection for oncogenically initiated cells and leukemogenesis specifically in the context of an aged hematopoietic system. Aging was associated with increased inflammation in the BM microenvironment, and induction of inflammation in young mice phenocopied aging-associated B lymphopoiesis. Conversely, a reduction of inflammation in aged mice via transgenic expression of alpha-1-antitrypsin or IL 37 preserved the function of B cell progenitors and prevented NRAS(V12)-mediated oncogenesis. We conclude that chronic inflammatory microenvironments in old age lead to reductions in the fitness of B cell progenitor populations. This reduced progenitor pool fitness engenders selection for cells harboring oncogenic mutations, in part due to their ability to correct aging-associated functional defects. Thus, modulation of inflammation--a common feature of aging--has the potential to limit aging-associated oncogenesis. PMID- 26551683 TI - Rabbit antithymocyte globulin-induced serum sickness disease and human kidney graft survival. AB - BACKGROUND: Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and alpha-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment. METHODS: We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Donnees Informatisees et Validees en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation. RESULTS: SSD was significantly associated with long term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients. CONCLUSION: In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients. FUNDING: This study was funded by Societe d'Acceleration du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation. PMID- 26551686 TI - From single chemicals to mixtures--reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow. AB - The aquatic environment is polluted with thousands of chemicals. It is currently unclear which of these pose a significant threat to aquatic biota. The typical exposure scenario is now represented by a widespread blanket of contamination composed of myriads of individual pollutants-each typically present at a low concentration. The synthetic steroids, 17alpha-ethinylestradiol and levonorgestrel, have been widely reported to be present in the aquatic environment in the low ng to sub-ng/l range. They are widely used in contraceptive formulations, both individually and in combination. Our research employed the fathead minnow (Pimephales promelas) 21 day 'pair-breeding' assay to assess reproductive output when pairs of fish were exposed to the single chemicals at low environmentally relevant concentrations, and then to a binary mixture of them. A variety of endpoints were assessed, including egg production, which was inhibited in a concentration-dependent manner by both the individual chemicals and the mixture. Significant, sex specific effects were also seen with both chemicals, at differing levels of biological organisation. Plasma concentrations of EE2 and levonorgestrel were predicted and in the case of levonorgestrel measured, and compared with the human therapeutic plasma concentrations (Read-Across approach) to support the interpretation of the results. A novel quantitative method was developed for the data analysis, which ensured a suitable endpoint for the comparative mixture assessment. This approach compares the reproductive performance from individual pairs of fish during chemical exposure to its pre-treatment performance. The responses from the empirical mixture study were compared to predictions derived from the single substance data. We hypothesised combined responses which were best described by the concept of concentration addition, and found no clear indications against this additivity expectation. However, the effect profiles support the current knowledge that both compounds act in different ways to reduce egg production in fish, and suggest that probably response addition (also called Independent action) is the more appropriate mixture model in this case. PMID- 26551684 TI - Blood kinetics of Ebola virus in survivors and nonsurvivors. AB - BACKGROUND: Infection with Ebola virus (EBOV) results in a life-threatening disease, with reported mortality rates between 50%-70%. The factors that determine patient survival are poorly understood; however, clinical observations indicate that EBOV viremia may be associated with fatal outcome. We conducted a study of the kinetics of Zaire EBOV viremia in patients with EBOV disease (EVD) who were managed at an Ebola Treatment Centre in Sierra Leone during the recent West African outbreak. METHODS: Data from 84 EVD patients (38 survivors, 46 nonsurvivors) were analyzed, and EBOV viremia was quantified between 2 and 13 days after symptom onset. Time since symptom onset and clinical outcome were used as independent variables to compare EBOV viral kinetics in survivors and nonsurvivors. RESULTS: In all patients, EBOV viremia kinetics was a quadratic function of time; however, EBOV viremia was 0.94 logarithm (log) copies per ml (cp/ml) (P = 0.011) higher in nonsurvivors than in survivors from day 2 after the onset of symptoms. Survivors reached peak viremia levels at an earlier time after symptom onset than nonsurvivors (day 5 versus day 7) and had lower mean peak viremia levels compared with nonsurvivors (7.46 log cp/ml; 95% CI, 7.17-7.76 vs. 8.60 log cp/ml; 95% CI, 8.27-8.93). Before reaching peak values, EBOV viremia similarly increased both in survivors and nonsurvivors; however, the decay of viremia after the peak was much stronger in survivors than in nonsurvivors. CONCLUSION: Our results demonstrate that plasma concentrations of EBOV are markedly different between survivors and nonsurvivors at very early time points after symptom onset and may be predicative of outcome. Further studies focused on the early phase of the disease will be required to identify the causal and prognostic factors that determine patient outcome. FUNDING: Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY's private donations; and Royal Engineers for DFID-UK. PMID- 26551685 TI - Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer. AB - Mutations in genes encoding chromatin-remodeling proteins are often identified in a variety of cancers. For example, the histone demethylase JARID1C is frequently inactivated in patients with clear cell renal cell carcinoma (ccRCC); however, it is largely unknown how JARID1C dysfunction promotes cancer. Here, we determined that JARID1C binds broadly to chromatin domains characterized by the trimethylation of lysine 9 (H3K9me3), which is a histone mark enriched in heterochromatin. Moreover, we found that JARID1C localizes on heterochromatin, is required for heterochromatin replication, and forms a complex with established players of heterochromatin assembly, including SUV39H1 and HP1alpha, as well as with proteins not previously associated with heterochromatin assembly, such as the cullin 4 (CUL4) complex adaptor protein DDB1. Transcription on heterochromatin is tightly suppressed to safeguard the genome, and in ccRCC cells, JARID1C inactivation led to the unrestrained expression of heterochromatic noncoding RNAs (ncRNAs) that in turn triggered genomic instability. Moreover, ccRCC patients harboring JARID1C mutations exhibited aberrant ncRNA expression and increased genomic rearrangements compared with ccRCC patients with tumors endowed with other genetic lesions. Together, these data suggest that inactivation of JARID1C in renal cancer leads to heterochromatin disruption, genomic rearrangement, and aggressive ccRCCs. Moreover, our results shed light on a mechanism that underlies genomic instability in sporadic cancers. PMID- 26551687 TI - Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae. AB - The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. PMID- 26551688 TI - The long-term survival of Propionibacterium freudenreichii in a context of nutrient shortage. AB - AIMS: Propionibacterium freudenreichii is an actinobacterium widely used in dairy industry during the ripening process of Swiss-type cheeses and which presents probiotic properties. P. freudenreichii is reportedly a hardy bacterium, able to survive during the cheese-making process and when subjected to digestive stresses. During this study the long-term survival (LTS) of P. freudenreichii was investigated for 11 days by means of phenotypic characterization in a culture medium without the addition of any nutrients. METHODS AND RESULTS: For 11 days, in a non-nutrient supplemented culture medium, eight strains were monitored by measuring their optical density, counting colony-forming units (CFU) and using LIVE/DEAD staining and microscopy observation. Under these conditions, all strains displayed high survival rates in the culture medium, their culturability reaching more than 9 log10 CFU ml(-1) after 2 days. After 11 days, this value ranged from 7.8 to 8.2 log10 CFU ml(-1) depending on the strain, and at least 50% of the P. freudenreichii population displayed an intact envelope. As lysis of part of a bacterial population may be a microbial strategy to recover nutrients, in CIRM-BIA 138 (the strain with the highest population at day 11), cell lysis was assessed by quantifying intact bacterial cells using qPCR targeting the housekeeping gene tuf. No lysis was observed. CONCLUSION: Taken together, our results suggest that P. freudenreichii strains use a viable but nonculturable state to adapt to the LTS phase. SIGNIFICANCE AND IMPACT OF THE STUDY: Assessing the viability of P. freudenreichii and understanding their mechanisms for survival should be of great interest regarding their potential probiotic applications. PMID- 26551689 TI - TSPO as a target for glioblastoma therapeutics. AB - The translocator protein (TSPO) is an 18-kDa five-transmembrane protein, which is primarily found in the outer mitochondrial membrane. Levels of this protein are up-regulated in the most aggressive and common glioma, glioblastoma multiforme (GM). Levels of TSPO also correlate with GM clinical outcome, suggesting that TSPO may be a novel GM diagnostic imaging agent. Therapeutically, targeting the TSPO may provide a mechanism to abrogate the apoptotic-resistant, invasive and aggressive nature of GM and may also provide a way of targeting other anti-cancer treatments to GM sites. This review highlights recent progress in research on TSPO-based diagnostic imaging and therapeutics for GM. PMID- 26551690 TI - Targeting mitochondrial energy metabolism with TSPO ligands. AB - The translocator protein (18 kDa) (TSPO) resides on the outer mitochondrial membrane where it is believed to participate in cholesterol transport and steroid hormone synthesis. Although it is almost ubiquitously expressed, what TSPO does in non-steroidogenic tissues is largely unexplored. Recent studies report changes in glucose homoeostasis and cellular energy production when TSPO function is modulated by selective ligands or by genetic loss-of-function. This review summarizes findings that connect TSPO function with the regulation of mitochondrial energy metabolism. The juxtaposition of TSPO at the cytosolic/mitochondrial interface and the existence of endogenous ligands that are regulated by metabolism suggest that TSPO functions to adapt mitochondrial to cellular metabolism. From a pharmacological perspective the specific up regulation of TSPO in neuro-inflammatory and injury-induced conditions make TSPO an interesting, druggable target of mitochondrial metabolism. PMID- 26551672 TI - Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. AB - We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease. PMID- 26551691 TI - TSPO is a REDOX regulator of cell mitophagy. AB - The mitochondrial 18-kDa translocator protein (TSPO) was originally discovered as a peripheral binding site of benzodiazepines to be later described as a core element of cholesterol trafficking between cytosol and mitochondria from which the current nomenclature originated. The high affinity it exhibits with chemicals (i.e. PK11195) has generated interest in the development of mitochondrial based TSPO-binding drugs for in vitro and in vivo analysis. Increased TSPO expression is observed in numerous pathologies such as cancer and inflammatory conditions of the central nervous system (CNS) that have been successfully exploited via protocols of positron emission tomography (PET) imaging. We endeavoured to dissect the molecular role of TSPO in mitochondrial cell biology and discovered a functional link with quality control mechanisms operated by selective autophagy. This review focuses on the current understanding of this pathway and focuses on the interplay with reactive oxygen species (ROS) and the voltage-dependent anion channel (VDAC), to which TSPO binds, in the regulation of cell mitophagy and hence homoeostasis of the mitochondrial network as a whole. PMID- 26551692 TI - Guwiyang Wurra--'Fire Mouse': a global gene knockout model for TSPO/PBR drug development, loss-of-function and mechanisms of compensation studies. AB - The highly conserved 18-kDa translocator protein (TSPO) or peripheral benzodiazepine receptor (PBR), is being investigated as a diagnostic and therapeutic target for disease conditions ranging from inflammation to neurodegeneration and behavioural illnesses. Many functions have been attributed to TSPO/PBR including a role in the mitochondrial permeability transition pore (MPTP), steroidogenesis and energy metabolism. In this review, we detail the recent developments in determining the physiological role of TSPO/PBR, specifically based on data obtained from the recently generated Tspo knockout mouse models. In addition to defining the role of TSPO/PBR, we also describe the value of Tspo knockout mice in determining the selectivity, specificity and presence of any off-target effects of TSPO/PBR ligands. PMID- 26551693 TI - Targeting the 18-kDa translocator protein: recent perspectives for neuroprotection. AB - The translocator protein (TSPO, 18 kDa), mainly localized in the outer mitochondrial membrane of steroidogenic tissues, is involved in several cellular functions. TSPO level alterations have been reported in a number of human disorders, particularly in cancer, psychiatric and neurological diseases. In the central nervous system (CNS), TSPO is usually expressed in glial cells, but also in some neuronal cell types. Interestingly, the expression of TSPO on glial cells rises after brain injury and increased TSPO expression is often observed in neurological disorders, gliomas, encephalitis and traumatic injury. Since TSPO is up-regulated in brain diseases, several structurally different classes of ligands targeting TSPO have been described as potential diagnostic or therapeutic agents. Recent researches have reported that TSPO ligands might be valuable in the treatment of brain diseases. This review focuses on currently available TSPO ligands, as useful tools for the treatment of neurodegeneration, neuro inflammation and neurotrauma. PMID- 26551694 TI - Structure of the mammalian TSPO/PBR protein. AB - The 3D structure of the 18-kDa transmembrane (TM) protein TSPO (translocator protein)/PBR (peripheral benzodiazepine receptor), which contains a binding site for benzodiazepines, is important to better understand its function and regulation by endogenous and synthetic ligands. We have recently determined the structure of mammalian TSPO/PBR in complex with the diagnostic ligand PK11195 [1 (2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; Jaremko et al. (2014) Science 343: , 1363-1366], providing for the first time atomic level insight into the conformation of this protein, which is up-regulated in various pathological conditions including Alzheimer's disease and Parkinson's disease. Here, we review the studies which have probed the structural properties of mammalian TSPO/PBR as well as the homologues bacterial tryptophan-rich sensory proteins (TspOs) over the years and provide detailed insight into the 3D structure of mouse TSPO (mTSPO)/PBR in complex with PK11195. PMID- 26551695 TI - Translocator protein: pharmacology and steroidogenesis. AB - The translocator protein (TSPO; 18k Da) is an evolutionarily conserved outer mitochondrial membrane (OMM) protein highly expressed in steroid-synthesizing cells and found to possess a number of physiological and drug-binding partners. Extensive pharmacological, biochemical and cell biological research over the years has led to a model of TSPO involvement in mitochondrial cholesterol transport and promotion of steroid synthesis, a model guiding the design of drugs useful in stimulating neurosteroid synthesis and alleviating psychopathological symptoms. The involvement of TSPO in these processes has been called into question; however, with the publication of TSPO-deletion mouse models which saw no changes in steroid production. Here, we review work characterizing TSPO in steroidogenesis and offer perspective to research into TSPO pharmacology and its involvement in steroid biosynthesis. PMID- 26551696 TI - The 18-kDa mitochondrial translocator protein in gliomas: from the bench to bedside. AB - The 18-kDa mitochondrial translocator protein (TSPO) is known to be highly expressed in several types of cancer, including gliomas, whereas expression in normal brain is low. TSPO functions in glioma are still incompletely understood. The TSPO can be quantified pre-operatively with molecular imaging making it an ideal candidate for personalized treatment of patient with glioma. Studies have proposed to exploit the TSPO as a transporter of chemotherapics to selectively target tumour cells in the brain. Our studies proved that positron emission tomography (PET)-imaging can contribute to predict progression of patients with glioma and that molecular imaging with TSPO-specific ligands is suitable to stratify patients in view of TSPO-targeted treatment. Finally, we proved that TSPO in gliomas is predominantly expressed by tumour cells. PMID- 26551698 TI - TSPO: functions and applications of a mitochondrial stress response pathway. AB - The mitochondrial outer membrane protein TSPO (translocator protein) lies in a privileged position at the interface between mitochondrion and cytosol. Since the initially discovery, nearly forty years ago, it has generated major interest among various disciplines of modern experimental and applied biomedicine. The focused meeting we have organized aimed at summarizing the state of the art knowledge on TSPO and the discipline-based segregated concepts that have made this an exciting and active field of science. The scientists who have generously contributed the event have agreed to generate a special issue here published- stemmed from the discussion of the vent. This consists in a series of contributions via which the know-how is shared aiming to inspire current and future endeavours to validate and accelerate the impact of TSPO science in human pathophysiology and clinical applications. PMID- 26551697 TI - The methodology of TSPO imaging with positron emission tomography. AB - The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [(11)C]-(R)-PK11195, a radiolabelled specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers. PMID- 26551699 TI - NRF2 and microRNAs: new but awaited relations. AB - The nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor is a key player in the cellular antioxidant response and it also controls various other functions in a cell-type specific manner. Due to these key functions, a tight control of NRF2 expression and activity is essential. This regulation is exerted at multiple levels, including transcriptional regulation and proteasomal degradation. Recent studies revealed important roles of miRNAs (miRs) in the control of NRF2 activity through direct targeting of the NRF2 mRNA and of mRNAs encoding proteins that control the level and activity of NRF2. In addition, NRF2 itself has been identified as a regulator of miRs, which exert some of the functions of NRF2 in metabolic regulation and also novel functions in the regulation of cell adhesion. Here, we summarize the roles and mechanisms of action of miRs in the regulation of NRF2 activity and as downstream effectors of this transcription factor. PMID- 26551700 TI - The spatiotemporal regulation of the Keap1-Nrf2 pathway and its importance in cellular bioenergetics. AB - The Kelch-like ECH associated protein 1 (Keap1)-NF-E2 p45-related factor 2 (Nrf2) pathway regulates networks of proteins that protect against the cumulative damage of oxidants, electrophiles and misfolded proteins. The interaction between transcription factor Nrf2 and its main negative cytoplasmic regulator Keap1 follows a cycle whereby the protein complex sequentially adopts two conformations: 'open', in which Nrf2 binds to one monomer of Keap1, followed by 'closed', in which Nrf2 interacts with both members of the Keap1 dimer. Electrophiles and oxidants (inducers) are recognized by cysteine sensors within Keap1, disrupting its ability to target Nrf2 for ubiquitination and degradation. Consequently, the protein complex accumulates in the 'closed' conformation, free Keap1 is not regenerated and newly synthesized Nrf2 is stabilized to activate target-gene transcription. The prevailing view of the Keap1-Nrf2 pathway, for which there exists a wealth of experimental evidence, is that it lies at the heart of cellular defence, playing crucial roles in adaptation and survival under conditions of stress. More recently, the significance of Nrf2 in intermediary metabolism and mitochondrial physiology has also been recognized, adding another layer of cytoprotection to the repertoire of functions of Nrf2. One way by which Nrf2 influences mitochondrial activity is through increasing the availability of substrates (NADH and FADH2) for respiration. Another way is through accelerating fatty acid oxidation (FAO). These findings reinforce the reciprocal relationship between oxidative phosphorylation and the cellular redox state, and highlight the key role of Nrf2 in regulating this balance. PMID- 26551701 TI - Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of beta-TrCP and GSK-3. AB - Nuclear factor-erythroid 2 p45 (NF-E2 p45)-related factor 2 (Nrf2) is a master regulator of redox homoeostasis that allows cells to adapt to oxidative stress and also promotes cell proliferation. In this review, we describe the molecular mechanisms by which oxidants/electrophilic agents and growth factors increase Nrf2 activity. In the former case, oxidants/electrophiles increase the stability of Nrf2 by antagonizing the ability of Kelch-like ECH-associated protein 1 (Keap1) to target the transcription factor for proteasomal degradation via the cullin-3 (Cul3)-RING ubiquitin ligase CRL(Keap1). In the latter case, we speculate that growth factors increase the stability of Nrf2 by stimulating phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB)/Akt signalling, which in turn results in inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) and in doing so prevents the formation of a DSGIS motif-containing phosphodegron in Nrf2 that is recognized by the beta-transducin repeat-containing protein (beta TrCP) Cul1-based E3 ubiquitin ligase complex SCF(beta-TrCP). We present data showing that in the absence of Keap1, the electrophile tert-butyl hydroquinone (tBHQ) can stimulate Nrf2 activity and induce the Nrf2-target gene NAD(P)H: quinone oxidoreductase-1 (NQO1), whilst simultaneously causing inhibitory phosphorylation of GSK-3beta at Ser(9). Together, these observations suggest that tBHQ can suppress the ability of SCF(beta-TrCP) to target Nrf2 for proteasomal degradation by increasing PI3K-PKB/Akt signalling. We also propose a scheme that explains how other protein kinases that inhibit GSK-3 could stimulate induction of Nrf2-target genes by preventing formation of the DSGIS motif-containing phosphodegron in Nrf2. PMID- 26551702 TI - Dissecting molecular cross-talk between Nrf2 and NF-kappaB response pathways. AB - In most tissues, cells are exposed to frequent changes in levels of oxidative stress and inflammation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappaB (NF-kappaB) are the two key transcription factors that regulate cellular responses to oxidative stress and inflammation respectively. Pharmacological and genetic studies suggest that there is functional cross-talk between these two important pathways. The absence of Nrf2 can exacerbate NF kappaB activity leading to increased cytokine production, whereas NF-kappaB can modulate Nrf2 transcription and activity, having both positive and negative effects on the target gene expression. This review focuses on the potentially complex molecular mechanisms that link the Nrf2 and NF-kappaB pathways and the importance of designing more effective therapeutic strategies to prevent or treat a broad range of neurological disorders. PMID- 26551703 TI - Redox-based regulation of neural stem cell function and Nrf2. AB - Neural stem cells (NSCs) play vital roles in the development and maintenance of brain tissues throughout life. They can also potentially act as powerful sources of regeneration and repair during pathology to replace degenerating cells and counteract deleterious changes in the tissue microenvironment. However, both aging and neurodegeneration involve an up-regulation of processes, such as oxidative stress, inflammation, somatic mutations, and reduction in growth factors in neural tissues, which threaten the robust functioning of NSCs. Nevertheless, recent evidence also indicates that NSCs may possess the intrinsic capability to cope with such stressors in their microenvironment. Whereas the mechanisms governing the responses of NSCs to stress are diverse, a common theme that is emerging suggests that underlying changes in intracellular redox status are crucial. Here we discuss such redox-based regulation of NSCs, particularly in relation to nuclear erythroid factor 2-like 2 (Nrf2), which is a key cellular stress resistance factor, and its implications for successfully harnessing NSC therapeutic potential towards developing cell-based therapeutics for nervous system disorders. PMID- 26551704 TI - Interplay between cytosolic disulfide reductase systems and the Nrf2/Keap1 pathway. AB - NADPH transfers reducing power from bioenergetic pathways to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR) to support essential reductive systems. Surprisingly, it was recently shown that mouse livers lacking both TrxR1 and GR ('TR/GR-null') can sustain redox (reduction-oxidation) homoeostasis using a previously unrecognized NADPH-independent source of reducing power fuelled by dietary methionine. The NADPH-dependent systems are robustly redundant in liver, such that disruption of either TrxR1 or GR alone does not cause oxidative stress. However, disruption of TrxR1 induces transcription factor Nrf2 (nuclear factor erythroid-derived 2-like-2) whereas disruption of GR does not. This suggests the Nrf2 pathway responds directly to the status of the thioredoxin-1 (Trx1) system. The proximal regulator of Nrf2 is Keap1 (Kelch-like ECH-associated protein-1), a cysteine (Cys)-rich protein that normally interacts transiently with Nrf2, targeting it for degradation. During oxidative stress, this interaction is stabilized, preventing degradation of newly synthesized Nrf2, thereby allowing Nrf2 accumulation. Within the Trx1 system, TrxR1 and peroxiredoxins (Prxs) contain some of the most reactive nucleophilic residues in the cell, making them likely targets for oxidants or electrophiles. We propose that Keap1 activity and therefore Nrf2 is regulated by interactions of Trx1 system enzymes with oxidants. In TR/GR-null livers, Nrf2 activity is further induced, revealing that TrxR independent systems also repress Nrf2 and these might be induced by more extreme challenges. PMID- 26551705 TI - Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism. AB - Cancer cells adapt their metabolism to their increased needs for energy and substrates for protein, lipid and nucleic acid synthesis. Nuclear erythroid factor 2-like 2 (Nrf2) pathway is usually activated in cancers and has been suggested to promote cancer cell survival mainly by inducing a large battery of cytoprotective genes. This mini review focuses on metabolic pathways, beyond cytoprotection, which can be directly or indirectly regulated by Nrf2 in cancer cells to affect their survival. The pentose phosphate pathway (PPP) is enhanced by Nrf2 in cancers and aids their growth. PPP has also been found to be up regulated in non-cancer tissues and other pathways, such as de novo lipogenesis, have been found to be repressed after activation of the Nrf2 pathway. The importance of these Nrf2-regulated metabolic pathways in cancer compared with non cancer state remains to be determined. Last but not least, the importance of context about Nrf2 and cancer is highlighted as the Nrf2 pathway may be activated in cancers but its pharmacological activators are useful in chemoprevention. PMID- 26551706 TI - Dysregulation of the Keap1-Nrf2 pathway in cancer. AB - Accumulating evidence suggests that dysregulation of the Kelch-like ECH associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway resulting in constitutively active Nrf2 and increased expression of cytoprotective Nrf2 target genes, has a pivotal role in cancer. Cancer cells are able to hijack the Keap1-Nrf2 system via multiple mechanisms leading to enhanced chemo- and radio-resistance and proliferation via metabolic reprogramming as well as inhibition of apoptosis. In this mini-review, we will describe the mechanisms leading to increased Nrf2 activity in cancer with a focus on the information achieved from large-scale multi-omics projects across various cancer types. PMID- 26551707 TI - Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1). AB - The nuclear erythroid 2-like 2 transcription factor (NRF2), is a major regulator of cellular redox balance. Although NRF2 activation is generally regarded as beneficial to human health, recent studies have identified that sustained NRF2 activation is over-represented in many cancers. This raises the question regarding the role of NRF2 activation in the development and progression of those cancers. This review focuses on the mechanisms and the effects of NRF2 activation in two hereditary cancer predisposition syndromes: hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary tyrosinemia type 1 (HT1). Because the cancer initiating mutations in these hereditary syndromes are well defined, they offer a unique opportunity to explore the roles of NRF2 activation in the early stages of carcinogenesis. Over the years, a variety of approaches have been utilized to study the biology of HLRCC and HT1. In HLRCC, in vitro studies have demonstrated the importance of NRF2 activation in sustaining cancer cell proliferation. In the mouse model of HT1 however, NRF2 activation seems to protect cells from malignant transformation. In both HT1 and HLRCC, NRF2 activation promotes the clearance of electrophilic metabolites, enabling cells to survive cancer-initiating mutations. Biological insights gained from the hereditary syndromes' studies may shed light on to the roles of NRF2 activation in sporadic tumours. PMID- 26551708 TI - Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress. AB - Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre clinical identification of chemicals and drugs with toxic liability in humans. PMID- 26551710 TI - Frequency modulated translocational oscillations of Nrf2, a transcription factor functioning like a wireless sensor. AB - The discovery that nuclear factor erythroid 2-related factor 2 (Nrf2) undergoes translocational oscillations from cytoplasm to nucleus in human cells with frequency modulation linked to activation of a stress-stimulated cytoprotective response raises the prospect that the Nrf2 works mechanistically analogous to a wireless sensor. Herein, we consider how this new model of Nrf2 oscillation resolves previous inexplicable experimental findings on Nrf2 regulation and why it is fit-for-purpose. Further investigation is required to assess how generally applicable the oscillatory mechanism is and if characteristics of this regulatory control can be found in vivo. It suggests there are multiple, potentially re enforcing receptors for Nrf2 activation, indicating that potent Nrf2 activation for improved health and treatment of disease may be achieved through combination of Nrf2 system stimulants. PMID- 26551709 TI - Nrf2 as a master regulator of tissue damage control and disease tolerance to infection. AB - Damage control refers to those actions made towards minimizing damage or loss. Depending on the context, these can range from emergency procedures dealing with the sinking of a ship or to a surgery dealing with severe trauma or even to an imaginary company in Marvel comics, which repairs damaged property arising from conflicts between super heroes and villains. In the context of host microbe interactions, tissue damage control refers to an adaptive response that limits the extent of tissue damage associated with infection. Tissue damage control can limit the severity of infectious diseases without interfering with pathogen burden, conferring disease tolerance to infection. This contrasts with immune driven resistance mechanisms, which although essential to protect the host from infection, can impose tissue damage to host parenchyma tissues. This damaging effect is countered by stress responses that confer tissue damage control and disease tolerance to infection. Here we discuss how the stress response regulated by the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) acts in such a manner. PMID- 26551711 TI - Peptide and small molecule inhibitors of the Keap1-Nrf2 protein-protein interaction. AB - The transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2) up regulates the expression of a range of cytoprotective enzymes with antioxidant response elements in their promoter regions and thus can protect cells against oxidative damage. Increasing Nrf2 activity has been proposed as a therapeutic intervention in a range of chronic neurodegenerative conditions and cancer chemoprevention. One of the main mechanisms by which Nrf2 is negatively regulated involves an interaction with the ubiquitination facilitator protein, Kelch-like ECH-associated protein 1 (Keap1) that facilitates degradation of Nrf2. Inhibition of this process underlies the mode of action of a broad group of compounds that increase Nrf2 activity. A number of natural products, including the isothiocyanate sulforaphane, up-regulate Nrf2 by interacting with Keap1 in a covalent manner to stall its activity. Recently, a number of peptide and small molecule inhibitors of the protein-protein interaction (PPI) between Keap1 and Nrf2 have been described. These classes of compound have contrasting modes of action at the molecular level and there is emerging evidence that their biological activities have similarities and differences. This review describes the various classes of PPI inhibitor that have been described in the literature and the biological evaluations that have been performed. PMID- 26551713 TI - The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic. AB - The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, with gene called NFE2L2) is a master regulator of the antioxidant response. In the last decade, interest has intensified in this research area as its importance in several physiological and pathological processes has become widely recognized; these include redox signalling and redox homoeostasis, drug metabolism and disposition, intermediary metabolism, cellular adaptation to stress, chemoprevention and chemoresistance, toxicity, inflammation, neurodegeneration, lipogenesis and aging. Regulation of Nrf2 is complex and although much attention has focussed on its repression by Kelch-like ECH-associated protein-1 (Keap1), recently it has become increasingly apparent that it is also controlled by cross talk with other signalling pathways including the glycogen synthase kinase-3 (GSK 3)-beta-transducin repeat-containing protein (beta-TrCP) axis, ERAD (endoplasmic reticulum-associated degradation)-associated E3 ubiquitin-protein ligase (Hrd1, also called synoviolin), nuclear factor-kappa B (NF-kappaB), Notch and AMP kinase. Due to its beneficial role in several diseases, Nrf2 has become a major therapeutic target, with novel natural, synthetic and targeted small molecules currently under investigation to modulate the pathway and in clinical trials. PMID- 26551712 TI - Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention. AB - Nrf2 (nuclear factor erytheroid-derived-2-like 2) transcriptional programmes are activated by a variety of cellular stress conditions to maintain cellular homoeostasis. Under non-stress conditions, Nrf2 is under tight regulation by the ubiquitin proteasome system (UPS). Detailed mechanistic investigations have shown the Kelch-like ECH-associated protein 1 (Keap1)-cullin3 (Cul3)-ring-box1 (Rbx1) E3-ligase to be the primary Nrf2 regulatory system. Recently, both beta transducin repeat-containing E3 ubiquitin protein ligase (beta-TrCP) and E3 ubiquitin-protein ligase synoviolin (Hrd1) have been identified as novel E3 ubiquitin ligases that negatively regulate Nrf2 through Keap1-independent mechanisms. In addition to UPS-mediated regulation of Nrf2, investigations have revealed a cross-talk between Nrf2 and the autophagic pathway resulting in activation of Nrf2 in a non-canonical manner. In addition to regulation at the protein level, Nrf2 was recently shown to be regulated at the transcriptional level by oncogenic K-rat sarcoma (Ras). A consequence of these differential regulatory mechanisms is the dual role of Nrf2 in cancer: the canonical, protective role and the non-canonical 'dark-side' of Nrf2. Based on the protective role of Nrf2, a vast effort has been dedicated towards identifying novel chemical inducers of Nrf2 for the purpose of chemoprevention. On the other hand, upon malignant transformation, some cancer cells have a constitutively high level of Nrf2 offering a growth advantage, as well as rendering cancer cells resistant to chemotherapeutics. This discovery has led to a new paradigm in cancer treatment; the initially counterintuitive use of Nrf2 inhibitors as adjuvants in chemotherapy. Herein, we will discuss the mechanisms of Nrf2 regulation and how this detailed molecular understanding can be leveraged to develop Nrf2 modulators to prevent diseases, mitigate disease progression or overcome chemoresistance. PMID- 26551714 TI - Engineering activated protein C to maximize therapeutic efficacy. AB - The anticoagulant-activated protein C (APC) acts not solely as a crucial regulator of thrombus formation following vascular injury, but also as a potent signalling enzyme with important functions in the control of both acute and chronic inflammatory disease. These properties have been exploited to therapeutic effect in diverse animal models of inflammatory disease, wherein recombinant APC administration has proven to effectively limit disease progression. Subsequent clinical trials led to the use of recombinant APC (Xigris) for the treatment of severe sepsis. Although originally deemed successful, Xigris was ultimately withdrawn due to lack of efficacy and an unacceptable bleeding risk. Despite this apparent failure, the problems that beset Xigris usage may be tractable using protein engineering approaches. In this review, we detail the protein engineering approaches that have been utilized to improve the therapeutic characteristics of recombinant APC, from early studies in which the distinct anti-coagulant and signalling activities of APC were separated to reduce bleeding risk, to current attempts to enhance APC cytoprotective signalling output for increased therapeutic efficacy at lower APC dosage. These novel engineered variants represent the next stage in the development of safer, more efficacious APC therapy in disease settings in which APC plays a protective role. PMID- 26551715 TI - Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact. AB - Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition. PMID- 26551716 TI - The blood-brain barrier endothelium: a target for pro-inflammatory cytokines. AB - An intact functioning blood-brain barrier (BBB) is fundamental to proper homoeostatic maintenance and perfusion of the central nervous system (CNS). Inflammatory damage to the unique microvascular endothelial cell monolayer that constitutes the luminal BBB surface, leading to elevated capillary permeability, has been linked to various neurological disorders ranging from ischaemic stroke and traumatic brain injury, to neurodegenerative disease and CNS infections. Moreover, the neuroinflammatory cascade that typically accompanies BBB failure in these circumstances has been strongly linked to elevated levels of pro inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). This mini review will examine our current knowledge of how cytokines may dysregulate the interendothelial paracellular pathway leading to elevated BBB permeability. The mechanistic role of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase)-induced oxidative stress in these events will also be addressed. PMID- 26551718 TI - Dysregulation of the endothelium following Staphylococcus aureus infection. AB - The cardiovascular system is typically a sterile environment; however entry of a microorganism into the circulation can cause potentially life threatening cardiac and/or vascular disease. Staphylococcus aureus endothelial cell interactions are arguably the most important interactions in the pathogenesis of cardiovascular infection. These interactions can trigger cardiac valve destruction in the case of endocarditis, multi-organ dysfunction in the case of sepsis and coagulopathy. Here, we review the interactions between S. aureus and endothelial cells and discuss the implications of these interactions in the progression of cardiovascular infection. PMID- 26551717 TI - Novel insights into the regulation of cyclooxygenase-2 expression by platelet cancer cell cross-talk. AB - Platelets are activated by the interaction with cancer cells and release enhanced levels of lipid mediators [such as thromboxane (TX)A2 and prostaglandin (PG)E2, generated from arachidonic acid (AA) by the activity of cyclooxygenase (COX)-1], granule content, including ADP and growth factors, chemokines, proteases and Wnt proteins. Moreover, activated platelets shed different vesicles, such as microparticles (MPs) and exosomes (rich in genetic material such as mRNAs and miRNAs). These platelet-derived products induce several phenotypic changes in cancer cells which confer high metastatic capacity. A central event involves an aberrant expression of COX-2 which influences cell-cycle progression and contribute to the acquisition of a cell migratory phenotype through the induction of epithelial mesenchymal transition genes and down-regulation of E-cadherin expression. The identification of novel molecular determinants involved in the cross-talk between platelets and cancer cells has led to identify novel targets for anti-cancer drug development. PMID- 26551719 TI - Role of chemokine receptors CXCR4 and CXCR7 for platelet function. AB - Platelet-derived SDF-1alpha (stromal cell derived factor-alpha) mediates inflammation, immune defence and repair mechanisms at site of tissue injury. This review summarizes the relative expression of CXC chemokine receptor 4 (CXCR4) and CXCR7 in platelets, their dynamic trafficking in presence of ligands like chemokine C-X-C-motif ligand 11 (CXCL11), CXCL12 and MIF (macrophage migration inhibitory factor); how these receptors differentially mediate the functional and survival response to the chemokines CXCL11, CXCL12 and MIF. We further elaborate and emphasize the prognostic significance of platelet surface expression of CXCR4 CXCR7 in the context of coronary artery disease (CAD). SDF-1alpha/CXCL12, CXCL11, MIF effects mediated through CXCR4 and CXCR7 may play a regulatory role at the site of vascular and tissue inflammation, immune defence and repair where activated platelets reach as forerunners and function as critical players. PMID- 26551720 TI - The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease. AB - The intestinal epithelium represents one of our most important interfaces with the external environment. It must remain tightly balanced to allow nutrient absorption, but maintain barrier function and immune homoeostasis, a failure of which results in chronic infection or debilitating inflammatory bowel disease (IBD). The intestinal epithelium mainly consists of absorptive enterocytes and secretory goblet and Paneth cells and has recently come to light as being an essential modulator of immunity as opposed to a simple passive barrier. Each epithelial sub-type can produce specific immune modulating factors, driving innate immunity to pathogens as well as preventing autoimmunity. The enteroendocrine cells comprise just 1% of this epithelium, but collectively form the bodies' largest endocrine system. The mechanisms of enteroendocrine cell peptide secretion during feeding, metabolism and nutrient absorption are well studied; but their potential interactions with the enriched numbers of surrounding immune cells remain largely unexplored. This review focuses on alterations in enteroendocrine cell number and peptide secretion during inflammation and disease, highlighting the few in depth studies which have attempted to dissect the immune driven mechanisms that drive these phenomena. Moreover, the emerging potential of enteroendocrine cells acting as innate sensors of intestinal perturbation and secreting peptides to directly orchestrate immune cell function will be proposed. In summary, the data generated from these studies have begun to unravel a complex cross-talk between immune and enteroendocrine cells, highlighting the emerging immunoendocrine axis as a potential target for therapeutic strategies for infections and inflammatory disorders of the intestine. PMID- 26551721 TI - CD8+ T-cell senescence: no role for mTOR. AB - Aging is accompanied by immune decline leading to increased incidence of infections and malignancies, given the demographic shift of humans towards an older age the identification of strategies for the manipulation of immunity is an important goal. Evidence implicates mammalian target of rapamycin (mTOR) to be a key modulator of aging and the use of mTOR inhibitors has been shown to ameliorate much age-related pathology; however, recent data suggest that senescent CD8(+) T-cells function independently of mTOR. This review article will challenge the perceived dogma that mTOR universally controls CD8(+) T-cell function. PMID- 26551722 TI - Metabolic signatures linked to macrophage polarization: from glucose metabolism to oxidative phosphorylation. AB - Macrophages are present in a large variety of locations, playing distinct functions that are determined by its developmental origin and by the nature of the activators of the microenvironment. Macrophage activation can be classified as pro-inflammatory (M1 polarization) or anti-inflammatory-pro-resolution deactivation (M2), these profiles coexisting in the course of the immune response and playing a relevant functional role in the onset of inflammation (Figure 1). Several groups have analysed the metabolic aspects associated with macrophage activation to answer the question about what changes in the regulation of energy metabolism and biosynthesis of anabolic precursors accompany the different types of polarization and to what extent they are necessary for the expression of the activation phenotypes. The interest of these studies is to regulate macrophage function by altering their metabolic activity in a 'therapeutic way'. PMID- 26551723 TI - Manipulating membrane lipid profiles to restore T-cell function in autoimmunity. AB - Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T cells from patients with the autoimmune disease systemic lupus erythematosus (SLE). PMID- 26551724 TI - Liver X receptors in immune cell function in humans. AB - The liver X receptors (LXRs), LXRalpha and LXRbeta, are transcription factors with well-established roles in the regulation of lipid metabolism and cholesterol homeostasis. In addition, LXRs influence innate and adaptive immunity, including responses to inflammatory stimuli, proliferation and differentiation, migration, apoptosis and survival. However, the majority of work describing the role of LXRs in immune cells has been carried out in mouse models, and there are a number of known species-specific differences concerning LXR function. Here we review what is known about the role of LXRs in human immune cells, demonstrating the importance of these receptors in the integration of lipid metabolism and immune function, but also highlighting the need for a better understanding of the species, isoform, and cell-type specific effects of LXR activation. PMID- 26551725 TI - Metabolic regulation of natural killer cells. AB - Natural killer (NK) cells have key roles in anti-viral and anti-tumour immune responses. Recent research demonstrates that cellular metabolism is an important determinant for the function of pro-inflammatory immune cells, including activated NK cells. The mammalian target of rapamcyin (mTOR) complex 1 (mTORC1) has been identified as a key metabolic regulator that promotes glycolytic metabolism in multiple immune cell subsets. Glycolysis is integrally linked to pro-inflammatory immune responses such that activated NK cells and effector T cell subsets are reliant on sufficient glucose availability for maximal effector function. This article will discuss the regulation of cellular metabolism in NK cells as compared with that of T lymphocytes and discuss the implications for NK cell responses to viral infection and cancer. PMID- 26551726 TI - High Exposure to Organophosphate Flame Retardants in Infants: Associations with Baby Products. AB - Infant products containing polyurethane foam are commonly treated with organophosphate flame retardants (PFRs), including tris(1,3-dichloro-2 propyl)phosphate (TDCIPP) and triphenyl phosphate (TPHP). Infants may have greater exposure due to greater contact with these products, yet little is known about levels of exposure or the factors contributing to higher exposure. We recruited children age 2-18 months from North Carolina to investigate PFR exposure (n = 43; recruited 2014-2015). Parents provided information on potential sources and modifiers of exposure, and reported whether they owned common infant products. We measured five PFR metabolites in urine samples collected from children. TDCIPP and TPHP metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP)) were most commonly detected (>93% detect). Other metabolites were detected infrequently (<35% detect). Although we did not observe a clear age trend for infants, BDCIPP levels were substantially higher than those reported for adults (geometric mean = 7.3 ng/mL). The number of infant products owned was strongly associated with BDCIPP; children with >16 products had BDCIPP levels that were 6.8 times those with <13 (p = 0.02). Infants attending daycare centers also had higher BDCIPP levels (3.7 times those of others; p = 0.07), suggesting time spent in this microenvironment contributes to higher exposure. In contrast, DPHP levels were not related to products owned, time in different microenvironments, or behavior. PMID- 26551727 TI - Nodular lymphoid hyperplasia of the GI tract. PMID- 26551728 TI - A miraculous colonoscopy: from anus to mouth. PMID- 26551729 TI - Acute spinal cord infarction after EUS-guided celiac plexus neurolysis. PMID- 26551730 TI - EUS-guided cyanoacrylate injection for treatment of endoscopically obscured bleeding gastric varices. PMID- 26551731 TI - Cap-assisted endoscopic mucosal resection of large nonampullary duodenal polyps in MYH-associated polyposis syndrome. PMID- 26551732 TI - Robotic-assisted flexible colonoscopy: preliminary safety and efficiency in humans. AB - BACKGROUND AND AIMS: The flexible endoscope is used as a platform for minimally invasive interventions. However, control of the conventional endoscope and multiple instruments is difficult. Robotic assistance could provide a solution and better control for a single operator. A novel platform should also enable interventions in areas that are currently difficult to reach. This study evaluates the safety and efficacy of a robotic platform that guides a conventional endoscope through the large bowel. METHODS: Adult patients scheduled for routine diagnostic colonoscopy were included in this feasibility study. The endoscope was introduced using a robotic add-on to provide tip bending and air/water actuation. The endoscopist directly controlled the endoscope shaft. Upon cecal intubation, the add-on was detached and the procedure continued using conventional control. Primary evaluation parameters were the number of serious adverse events and the percentage of successful cecal intubations. RESULTS: The procedure was performed on 22 consecutive patients who all gave informed consent. There were no serious adverse events. Cecal intubation was successful in 15 patients (68%) using the robotic add-on. Six cases were completed after conversion to conventional control: 3 cases were converted to pass sharp angulation in the flexures and 3 cases were converted after technical difficulties. One case was not successful with either technique because of severe diverticulosis. CONCLUSIONS: The robotic add-on steering module allows safe endoscope intubation to reach intervention sites throughout the large bowel. The next step is to clinically evaluate complementary instrument and shaft-guiding modules in therapeutic procedures. PMID- 26551733 TI - Crash protectiveness to occupant injury and vehicle damage: An investigation on major car brands. AB - This study sets out to investigate vehicles' crash protectiveness on occupant injury and vehicle damage, which can be deemed as an extension of the traditional crash worthiness. A Bayesian bivariate hierarchical ordered logistic (BVHOL) model is developed to estimate the occupant protectiveness (OP) and vehicle protectiveness (VP) of 23 major car brands in Florida, with considering vehicles' crash aggressivity and controlling external factors. The proposed model not only takes over the strength of the existing hierarchical ordered logistic (HOL) model, i.e. specifying the order characteristics of crash outcomes and cross crash heterogeneities, but also accounts for the correlation between the two crash responses, driver injury and vehicle damage. A total of 7335 two-vehicle crash records with 14,670 cars involved in Florida are used for the investigation. From the estimation results, it's found that most of the luxury cars such as Cadillac, Volvo and Lexus possess excellent OP and VP while some brands such as KIA and Saturn perform very badly in both aspects. The ranks of the estimated safety performance indices are even compared to the counterparts in Huang et al. study [Huang, H., Hu, S., Abdel-Aty, M., 2014. Indexing crash worthiness and crash aggressivity by major car brands. Safety Science 62, 339 347]. The results show that the rank of occupant protectiveness index (OPI) is relatively coherent with that of crash worthiness index, but the ranks of crash aggressivity index in both studies is more different from each other. Meanwhile, a great discrepancy between the OPI rank and that of vehicle protectiveness index is found. What's more, the results of control variables and hyper-parameters estimation as well as comparison to HOL models with separate or identical threshold errors, demonstrate the validity and advancement of the proposed model and the robustness of the estimated OP and VP. PMID- 26551734 TI - Trends in local newspaper reporting of London cyclist fatalities 1992-2012: the role of the media in shaping the systems dynamics of cycling. AB - BACKGROUND: Successfully increasing cycling across a broad range of the population would confer important health benefits, but many potential cyclists are deterred by fears about traffic danger. Media coverage of road traffic crashes may reinforce this perception. As part of a wider effort to model the system dynamics of urban cycling, in this paper we examined how media coverage of cyclist fatalities in London changed across a period when the prevalence of cycling doubled. We compared this with changes in the coverage of motorcyclist fatalities as a control group. METHODS: Police records of traffic crashes (STATS19) were used to identify all cyclist and motorcyclist fatalities in London between 1992 and 2012. We searched electronic archives of London's largest local newspaper to identify relevant articles (January 1992-April 2014), and sought to identify which police-reported fatalities received any media coverage. We repeated this in three smaller English cities. RESULTS: Across the period when cycling trips doubled in London, the proportion of fatalities covered in the local media increased from 6% in 1992-1994 to 75% in 2010-2012. By contrast, the coverage of motorcyclist fatalities remained low (4% in 1992-1994 versus 5% in 2010-2012; p=0.007 for interaction between mode and time period). Comparisons with other English cities suggested that the changes observed in London might not occur in smaller cities with lower absolute numbers of crashes, as in these settings fatalities are almost always covered regardless of mode share (79-100% coverage for both cyclist and motorcyclist fatalities). CONCLUSION: In large cities, an increase in the popularity (and therefore 'newsworthiness') of cycling may increase the propensity of the media to cover cyclist fatalities. This has the potential to give the public the impression that cycling has become more dangerous, and thereby initiate a negative feedback loop that dampens down further increases in cycling. Understanding these complex roles of the media in shaping cycling trends may help identify effective policy levers to achieve sustained growth in cycling. PMID- 26551736 TI - Enhancing the linear flow of fine granules through the addition of elongated particles. AB - Sandglasses have been used to record time for thousands of years because of their constant flow rates; however, they now are drawing attention for their substantial scientific importance and extensive industrial applications. The presence of elongated particles in a binary granular system is believed to result in undesired flow because their shape implies a larger resistance to flow. However, our experiments demonstrate that the addition of elongated particles can substantially reduce the flow fluctuation of fine granules and produce a stable linear flow similar to that in an hourglass. On the basis of experimental data and previous reports of flow dynamics, we observed that the linear flow is driven by the "needle particle effect," including flow orientation, reduced agglomeration, and local perturbation. This phenomenon is observed in several binary granular systems, including fine granules and secondary elongated particles, which demonstrates that our simple method can be widely applied to the accurate measurement of granular flows in industry. PMID- 26551735 TI - Anticipatory activation of the unfolded protein response by epidermal growth factor is required for immediate early gene expression and cell proliferation. AB - The onco-protein epidermal growth factor (EGF) initiates a cascade that includes activation of the ERK and AKT signaling pathways and alters gene expression. We describe a new action of EGF-EGF receptor (EGFR), rapid anticipatory activation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR). Within 2 min, EGF elicits EGFR dependent activation of phospholipase C gamma (PLCgamma), producing inositol triphosphate (IP3), which binds to IP3 receptor (IP3R), opening the endoplasmic reticulum IP3R Ca(2+) channels, resulting in increased intracellular Ca(2+). This calcium release leads to transient and moderate activation of the IRE1alpha and ATF6alpha arms of the UPR, resulting in induction of BiP chaperone. Knockdown or inhibition of EGFR, PLCgamma or IP3R blocks the increase in intracellular Ca(2+). While blocking the increase in intracellular Ca(2+) by locking the IP3R calcium channel with 2-APB had no effect on EGF activation of the ERK or AKT signaling pathways, it abolished the rapid EGF-mediated induction and repression of gene expression. Knockdown of ATF6alpha or XBP1, which regulate UPR-induced chaperone production, inhibited EGF stimulated cell proliferation. Supporting biological relevance, increased levels of EGF receptor during tumor progression were correlated with increased expression of the UPR gene signature. Anticipatory activation of the UPR is a new role for EGF. Since UPR activation occurs in <2 min, it is an initial cell response when EGF binds EGFR. PMID- 26551737 TI - VEGFR-1 activation-induced MMP-9-dependent invasion in hepatocellular carcinoma. AB - AIM: VEGFR-1 can promote invasion through epithelial-mesenchymal transition induction in hepatocellular carcinoma (HCC). This study aims to elucidate VEGFR-1 impact on proteolytic enzymes profile involved with invasion. MATERIALS & METHODS: The effect on cell invasion was evaluated by invasive and migration assays with and without VEGFR-1 activation. The mechanism was investigated by real-time PCR, western blot and gelatin zymography using inhibitors for MMP-9. In total, 95 HCC patients were enrolled for its clinical value evaluation. RESULTS: VEGFR-1 activation induced invasion in HCC cells with an increase in the expression and activity of MMP-9 and Snail. MMP-9 blockage effectively inhibited VEGFR-1-induced invasion. High coexpression of both in HCC predicted a worse clinical outcome. CONCLUSION: Data show a novel VEGFR-1 activation-to-MMP-9 mechanism promoting HCC invasion. PMID- 26551739 TI - Greetings to the Reader. PMID- 26551740 TI - Regulation of TRPC6 ion channels in podocytes - Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases. AB - The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury. PMID- 26551741 TI - Radiofrequency ablation of focal atrial tachycardia: Benefit of electroanatomical mapping over conventional mapping. AB - BACKGROUND: Catheter ablation is a proven therapy of focal atrial tachycardia. However limited information is available about the additional value of electroanatomical over conventional mapping methods for this specific arrhythmia. METHODS: Consecutive catheter ablation procedures of FAT were analyzed in two cardiology centres. Only conventional mapping was used in 30 of the 60 procedures whereas additionally CARTO mapping was performed in another 30 procedures. Acute, six-month success rate, and procedural data were analyzed. RESULTS: Localization of ectopic foci is congruent with previously published data. There was no statistically significant difference between procedure time and fluoroscopy time using additionally CARTO mapping, compared to conventional mapping only. Acute success rate was higher in procedures guided by CARTO mapping than in procedures based on conventional mapping (27/30 vs. 18/30, p = 0.0081). During the 6-month follow-up period there was a better outcome (p = 0.045) in case of CARTO guided procedures (success: 11 cases, partial success: 12 cases, failure: 4 cases) compared to conventional mapping (success: 4 cases, partial success: 18 cases, failure: 7 cases). CONCLUSIONS: Catheter ablation of focal atrial tachycardias using the CARTO electroanatomical mapping system seems to provide higher acute and 6-month success rate compared to ablation using conventional mapping methods only. PMID- 26551738 TI - Ectopic lymphoid follicles: inducible centres for generating antigen-specific immune responses within tissues. AB - Lymphoid neogenesis is traditionally viewed as a pre-programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen-specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto-immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease. PMID- 26551742 TI - Characteristics of cardiorespiratory output determining factors among 11-19-year old boys at rest and during maximal load: Its impact on systolic hypertension. AB - As consequence of the expansion of sedentary lifestyle among schoolchildren the prevalence of particular symptoms related to decreased cardiorespiratory fitness increases. The purpose of this study was twofolds, on one hand to compare boys in three developmental groups: second childhood (G1), puberty (G2), young adult (G3) and on the other hand to compare groups classified on resting systolic blood pressure (RSBP) to differentiate cardiorespiratory output determining factors both at rest and at maximal load. Randomly selected apparently healthy boys were assessed, all subjects (n = 282) performed an incremental treadmill test until fatigue. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), and oxygen consumption were measured. Resting HR was higher and resting SBP and DBP were lower in the G1 as compared to G2 and G3 (p < 0.05) but not differed at maximal loads. However indicators of cardiovascular load differed between groups. The oxygen pulse and Q were the lowest in the G1 and increased significantly between groups (p < 0.05). In conclusion based on our data we can suggest that there is an observable development of hypertension associated with maturation and cardiac output determining factors. PMID- 26551743 TI - Oscillation of tissue oxygen index in non-exercising muscle during exercise. AB - The purpose of the present study was to examine how oscillation of tissue oxygen index (TOI) in non-exercising exercise is affected during high-intensity and low intensity exercises. Three exercises were performed with exercise intensities of 30% and 70% peak oxygen uptake (Vo(2)peak) for 12 min and with exercise intensity of 70% Vo(2)peak for 30 s. TOI in non-exercising muscle (biceps brachii) during the exercises for 12 min was determined by nearinfrared spectroscopy. TOI in the non-exercising muscle during the exercises was analyzed by fast Fourier transform (FFT) to obtain power spectra density (PSD). The frequency at which maximal PSD appeared (Fmax) during the exercise with 70% Vo(2)peak for 12 min (0.00477 +/- 0.00172 Hz) was significantly lower than that during the exercise with 30% Vo2peak for 12 min (0.00781 +/- 0.00338 Hz). There were significant differences in blood pH and blood lactate between the exercise with 70% Vo(2)peak and the exercise with 30% Vo(2)peak. It is concluded that TOI in nonexercising muscle oscillates during low-intensity exercise as well as during high-intensity exercise and that the difference in Fmax between the two exercises is associated with the difference in increase in blood lactate derived from the exercise. PMID- 26551744 TI - Plasma volume after heat acclimation: Variations due to season, fitness and methods of measurement. AB - PURPOSE: The reported magnitude of plasma volume increase (Delta%PV) following heat acclimation (HA) varies widely. Variations may result from differences in measurement techniques, season and subjects' fitness. This report compares direct and indirect measurements of Delta%PV after 10 days of HA from studies in winter (WIN, n = 8) and summer (SUM, n = 10) in men, age 21-43 yr, at two fitness levels (VO(2)max: 35 and 51 ml/min/kg). Direct measurements were made before and after HA (cycling at 30% of VO(2)max at 50 degrees C, for 100 min/day) by carbon monoxide (CO) rebreathing and compared with indirect estimates from changes in hematocrit, hemoglobin and plasma protein concentration. RESULTS: Overall, Delta%PV by CO was small (2.9%) and greater in SUM than WIN (5.0 vs. 0.3%). Red cell, blood and plasma volumes/kg lean body mass increased in SUM and decreased in WIN, the difference being significant, and Delta%PV by CO was similar for high and low VO(2)max. CONCLUSION: Overall, indirect estimates of Delta%PV by hemoglobin and hematocrit were similar to CO, but tended to differentiate by fitness and not season. The difference in THb increase in SUM and decrease in WIN was significant. This probably accounts for the differences from the seasonal and fitness results by the direct CO method. PMID- 26551745 TI - Heat stress attenuates skeletal muscle atrophy of extensor digitorum longus in streptozotocin-induced diabetic rats. AB - To investigate whether heat stress attenuates skeletal muscle atrophy of the extensor digitorum longus (EDL) muscle in streptozotocin-induced diabetic rats, 12-week-old male Wistar rats were randomly assigned to four groups (n = 6 per group): control (Con), heat stress (HS), diabetes mellitus (DM), and diabetes mellitus/heat stress (DM + HS). Diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg). Heat stress was induced in the HS and DM + HS groups by immersion of the lower half of the body in hot water at 42 degrees C for 30 min; it was initiated 7 days after injection of streptozotocin, and was performed once a day, five times a week for 3 weeks. The muscle fiber cross sectional area of EDL muscles from diabetic and non-diabetic rats was determined; heat stress protein (HSP) 72 and HSP25 expression levels were also analyzed by western blotting. Diabetes-induced muscle fiber atrophy was attenuated upon heat stress treatment in diabetic rats. HSP72 and HSP25 expression was upregulated in the DM + HS group compared with the DM group. Our findings suggest that heat stress attenuates atrophy of the EDL muscle by upregulating HSP72 and HSP25 expression. PMID- 26551746 TI - Examination of the interaction of different lighting conditions and chronic mild stress in animal model. AB - We examined the effects of different shift work schedules and chronic mild stress (CMS) on mood using animal model. The most common international shift work schedules in nursing were applied by three groups of Wistar-rats and a control group with normal light-dark cycle. One subgroup from each group was subjected to CMS. Levels of anxiety and emotional life were evaluated in light-dark box. Differences between the groups according to independent and dependent variables were examined with one- and two-way analysis of variance, with a significance level defined at p < 0.05. Interaction of lighting regimen and CMS was proved to be significant according to time spent in the light compartment and the average number of changes between the light and dark compartments. Results of our examination confirm that the changes of lighting conditions evocate anxiety more prominently than CMS. No significant differences were found between the results of the low rotating group and the control group, supposing that this schedule is the least harmful to health. Our results on the association between the use of lighting regimens and the level of CMS provide evidence that the fast rotating shift work schedule puts the heaviest load on the organism of animals. PMID- 26551747 TI - A comparative study of the physical development and motor performance of mentally non-handicapped children and children with intellectual and development disabilities. AB - Several studies state that there might be a difference in the physical development and the motor performance of the mentally non-handicapped children and those with intellectual and development disabilities. The aim of our research was to compare the two groups from these aspects. The study included the assessment of the physical development and motor performance of altogether 225 primary school pupils (mentally non-handicapped and with intellectual and development disabilities) aged 8-11. The following indicators of physical development and build were examined: body height, body weight and body mass index (BMI), musculoskeletal plasticity index, biceps and triceps skinfold thickness. The motor tests included: 20 m dash, standing long jump, medicine-ball throwing, six minutes continuous running, obstacle race-test and a match test. We also examined the children's chronological (decimal) and morphological age. Data were analysed with SPSS programme. The differences between the averages were calculated with ANOVA and Fisher's LSD tests. The results show that the children with intellectual and development disabilities are in general less developed physically than non-handicapped children of the same age and sex. It is also concluded that in most motor tests the children with intellectual and development disabilities fall behind the non-handicapped ones. PMID- 26551748 TI - Effects of therapeutic horse riding on gait cycle parameters and some aspects of behavior of children with autism. AB - We studied effects of therapeutic riding on the development of children with autism. Experiments in walking is appropriate for assessing the coordination of movement and for following the changes. We found that therapeutic riding should be considered as a new form of rehabilitation. Twenty-six pupils (12 boys and 14 girls) of a special needs school participated in therapeutic riding. We analyzed walking twice during a school-term: full body analyses each time before and after one-month therapy. The research included a non-riding control group. All together 104 analyses were performed. We measured mental skills using Pedagogical Analysis and Curriculum (PAC) test consisting of four parts being communication, self care, motor skills and socialization. The Gait Cycle Analysis consists of the time-series analysis, the analysis of part of the gait cycle and the measurement of joint angles in each plane. We found significant differences between before and after the therapy in the length of the gait cycle that became more stable in the sagital plane and concluded that our results proved that horse therapy may be successfully used as an additional therapy for children with autism, and it may be a form of rehabilitation in cases when other therapies are not successful. PMID- 26551749 TI - Menstrual cycle phase effects free testosterone responses to prolonged aerobic exercise. AB - Research has shown that total testosterone (tT) levels in women increase acutely during a prolonged bout of aerobic exercise. Few studies, however, have considered the impact of the menstrual cycle phase on this response or have looked at the biologically active free testosterone (fT) form responses. Therefore, this study examined the fT concentration response independently and as a percentage (fT%) of tT to prolonged aerobic exercise during phases of the menstrual cycle with low estrogen-progesterone (L-EP; i.e., follicular phase) and high estrogen-progesterone (H-EP; i.e., luteal phase). Ten healthy, recreationally trained, eumennorrheic women (X +/- SD: age = 20 +/- 2 y, mass = 58.7 +/- 8.3 kg, body fat = 22.3 +/- 4.9 %, VO(2max) = 50.7 +/- 9.0 ml/kg/min) participated in a laboratory based study and completed a 60-minute treadmill run during the L-EP and H-EP menstrual phases at ~70% of VO(2max). Blood was drawn prior to (PRE), immediately after (POST) and following 30 minutes of recovery (30POST) with each 60-minute run. During H-EP, there was a significant increase in fT concentrations from PRE to POST (p < 0.01) while in L-EP fT levels were unchanged; which resulted in fT being significantly higher at H-EP POST versus L EP POST (p < 0.03). Area-under-the-curve (AUC) responses were calculated, for fT the total AUC was greater in H-EP than L-EP (p < 0.04). There was no significant interaction of fT% between phases and exercise sampling time. There was, however, a main effect for exercise where fT% POST was a greater proportion of tT than at PRE (p < 0.01). In summary, hormonal changes associated with the menstrual cycle impact fT response to a prolonged aerobic exercise bout; specifically, there being higher levels under H-EP conditions. This suggests more biologically active T is available during exercise in this phase. This response may be a function of the higher core temperatures found with H-EP causing greater sex hormone binding protein release of T, or could be a function of greater degrees of glandular production. Further work is warranted to elucidate the mechanism of this occurrence. It is recommended that researchers examining T responses to exercise in women look at both tT and fT forms in order to have an accurate endocrine assessment in women. PMID- 26551750 TI - Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions. AB - Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis. PMID- 26551751 TI - Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation. AB - Inhalation of carbon black nanoparticles (CBNPs) causes pulmonary inflammation; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 mice were intratracheally instilled with 162 MUg CBNPs alongside vehicle controls. Lung tissues were examined 3h, and 1, 2, 3, 4, 5, 14, and 42 days (d) post-exposure. Global gene expression and pulmonary inflammation were assessed. DNA damage was evaluated in bronchoalveolar lavage (BAL) cells and lung tissue using the comet assay. Increased neutrophil influx was observed at all time-points. DNA strand breaks were increased in BAL cells 3h post-exposure, and in lung tissues 2-5d post-exposure. Approximately 2600 genes were differentially expressed (+/- 1.5 fold; p <= 0.05) across all time-points in the lungs of exposed mice. Altered transcript levels were associated with immune inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common respiratory infectious diseases. Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3h post-exposure declining to base-levels by 3d, increasing again at 14 d, and then persisting to 42 d post-exposure. Thus, this single CBNP exposure that was equivalent to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42 d post-exposure, raising concern over the chronic effects of CBNP exposure. PMID- 26551752 TI - Integrative analysis of genes and miRNA alterations in human embryonic stem cells derived neural cells after exposure to silver nanoparticles. AB - Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200MUg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. PMID- 26551753 TI - Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos. AB - The toxicity mechanism of nanoparticles on vertebrate cardiovascular system is still unclear, especially on the low-level exposure. This study was to explore the toxic effect and mechanisms of low-dose exposure of silica nanoparticles (SiNPs) on cardiac function in zebrafish embryos via the intravenous microinjection. The dosage of SiNPs was based on the no observed adverse effect level (NOAEL) of malformation assessment in zebrafish embryos. The mainly cardiac toxicity phenotypes induced by SiNPs were pericardial edema and bradycardia but had no effect on atrioventricular block. Using o-Dianisidine for erythrocyte staining, the cardiac output of zebrafish embryos was decreased in a dose dependent manner. Microarray analysis and bioinformatics analysis were performed to screen the differential expression genes and possible pathway involved in cardiac function. SiNPs induced whole-embryo oxidative stress and neutrophil mediated cardiac inflammation in Tg(mpo:GFP) zebrafish. Inflammatory cells were observed in atrium of SiNPs-treated zebrafish heart by histopathological examination. In addition, the expression of TNNT2 protein, a cardiac contraction marker in heart tissue had been down-regulated compared to control group using immunohistochemistry. Confirmed by qRT-PCR and western blot assays, results showed that SiNPs inhibited the calcium signaling pathway and cardiac muscle contraction via the down-regulated of related genes, such as ATPase-related genes (atp2a1l, atp1b2b, atp1a3b), calcium channel-related genes (cacna1ab, cacna1da) and the regulatory gene tnnc1a for cardiac troponin C. Moreover, the protein level of TNNT2 was decreased in a dose-dependent manner. For the first time, our results demonstrated that SiNPs induced cardiac dysfunction via the neutrophil mediated cardiac inflammation and cardiac contraction in zebrafish embryos. PMID- 26551754 TI - Hyphenation of Hadamard Encoded Multiplexing Liquid Chromatography and Circular Dichroism Detection to Improve the Signal-to-Noise Ratio in Chiral Analysis. AB - The hyphenation of HPLC and circular dichroism (CD) detection is a useful analytical tool that can significantly facilitate the analysis (e.g., the assignment of the configuration) and quantitation of chiral compounds. HPLC-CD chromatograms often exhibit a low signal-to-noise ratio compared to chromatograms obtained by conventional UV detection. In this study we demonstrate for the first time the hyphenation of Hadamard encoded multiplexing HPLC with circular dichroism detection where positive and negative signals overlap. Here, a macro control of the HPLC instrument that was developed for conventional HPLC was implemented in HPLC-CD. In the chiral analysis of racemic samples, exemplified for warfarin, the signal-to-noise ratio could be enhanced by an order of magnitude. The presented results highlight the great modularity of the software controlled implementation of multiplexing and its facile transfer to other detection techniques. PMID- 26551756 TI - Genetic Correlation Between Schizophrenia and Epilepsy. PMID- 26551755 TI - Oriented Bioconjugation of Unmodified Antibodies to Quantum Dots Capped with Copolymeric Ligands as Versatile Cellular Imaging Tools. AB - Distinctive optical properties of inorganic quantum dot (QD) nanoparticles promise highly valuable probes for fluorescence-based detection methods, particularly for in vivo diagnostics, cell phenotyping via multiple markers or single molecule tracking. However, despite high hopes, this promise has not been fully realized yet, mainly due to difficulties at producing stable, nontoxic QD bioconjugates of negligible nonspecific binding. Here, a universal platform for antibody binding to QDs is presented that builds upon the controlled functionalization of CdSe/CdS/ZnS nanoparticles capped with a multidentate dithiol/zwitterion copolymer ligand. In a change-of-paradigm approach, thiol groups are concomitantly used as anchoring and bioconjugation units to covalently bind up to 10 protein A molecules per QD while preserving their long-term colloidal stability. Protein A conjugated to QDs then enables the oriented, stoichiometrically controlled immobilization of whole, unmodified antibodies by simple incubation. This QD-protein A immobilization platform displays remarkable antibody functionality retention after binding, usually a compromised property in antibody conjugation to surfaces. Typical QD-protein A-antibody assemblies contain about three fully functional antibodies. Validation experiments show that these nanobioconjugates overcome current limitations since they retain their colloidal stability and antibody functionality over 6 months, exhibit low nonspecific interactions with live cells and have very low toxicity: after 48 h incubation with 1 MUM QD bioconjugates, HeLa cells retain more than 80% of their cellular metabolism. Finally, these QD nanobioconjugates possess a high specificity for extra- and intracellular targets in live and fixed cells. The dithiol/zwitterion QD-protein A nanoconjugates have thus a latent potential to become an off-the-shelf tool destined to unresolved biological questions. PMID- 26551757 TI - Interaction of Charged Colloidal Particles at the Air-Water Interface. AB - We study, using Monte Carlo simulations, the interaction between charged colloidal particles confined to the air-water interface. The dependence of force on ionic strength and counterion valence is explored. For 1:1 electrolyte, we find that the electrostatic interaction at the interface is very close to the one observed in the bulk. On the other hand, for salts with multivalent counterions, an interface produces an enhanced attraction between like charged colloids. Finally, we explore the effect of induced surface charge at the air-water interface on the interaction between colloidal particles. PMID- 26551758 TI - Flow Cytometric Analysis of Mononuclear Phagocytes in Nondiseased Human Lung and Lung-Draining Lymph Nodes. AB - RATIONALE: The pulmonary mononuclear phagocyte system is a critical host defense mechanism composed of macrophages, monocytes, monocyte-derived cells, and dendritic cells. However, our current characterization of these cells is limited because it is derived largely from animal studies and analysis of human mononuclear phagocytes from blood and small tissue resections around tumors. OBJECTIVES: Phenotypic and morphologic characterization of mononuclear phagocytes that potentially access inhaled antigens in human lungs. METHODS: We acquired and analyzed pulmonary mononuclear phagocytes from fully intact nondiseased human lungs (including the major blood vessels and draining lymph nodes) obtained en bloc from 72 individual donors. Differential labeling of hematopoietic cells via intrabronchial and intravenous administration of antibodies within the same lobe was used to identify extravascular tissue-resident mononuclear phagocytes and exclude cells within the vascular lumen. Multiparameter flow cytometry was used to identify mononuclear phagocyte populations among cells labeled by each route of antibody delivery. MEASUREMENTS AND MAIN RESULTS: We performed a phenotypic analysis of pulmonary mononuclear phagocytes isolated from whole nondiseased human lungs and lung-draining lymph nodes. Five pulmonary mononuclear phagocytes were observed, including macrophages, monocyte-derived cells, and dendritic cells that were phenotypically distinct from cell populations found in blood. CONCLUSIONS: Different mononuclear phagocytes, particularly dendritic cells, were labeled by intravascular and intrabronchial antibody delivery, countering the notion that tissue and blood mononuclear phagocytes are equivalent systems. Phenotypic descriptions of the mononuclear phagocytes in nondiseased lungs provide a precedent for comparative studies in diseased lungs and potential targets for therapeutics. PMID- 26551759 TI - A bioanalytical assay to distinguish cellular uptake routes for liposomes. AB - Lipid-based nanoparticles are frequently used for drug or DNA delivery into mammalian cells. However it is difficult to determine whether such particles are taken up via endocytosis or fusion to the plasma membrane. Here, we propose a simple and reliable analytical method to do so based on the unique spectral properties of the fluorescent tracer BODIPY FL. At high local concentrations, this dye displays an additional red-shifted emission peak that is absent at low concentrations. In dye-loaded liposomes taken up by endocytosis, the local dye concentration did not significantly change upon internalization. Accordingly, unchanged fluorescence spectra were detected. When cells were incubated with liposomes able to fuse with the plasma membrane of mammalian cells, a reduction of local dye concentration and much weaker emission in the red-shifted peak were observed. The ratio of intensities in both fluorescence channels was shown to be a reliable indicator of the cellular uptake mechanism. PMID- 26551760 TI - Grapheme-Color Synesthesia and Posttraumatic Stress Disorder: Preliminary Results From the Veterans Health Study: Erratum. PMID- 26551761 TI - How intersectional constructions of sexuality, culture, and masculinity shape identities and sexual decision-making among men who have sex with men in coastal Kenya. AB - Men who have sex with men are increasingly recognised as one of the most vulnerable HIV risk groups in Kenya. Sex between men is highly stigmatised in Kenya, and efforts to provide sexual health services to men who have sex with men require a deeper understanding of their lived experiences; this includes how such men in Kenya construct their sexual identities and how these constructions affect sexual decision-making. Adult self-identified men who have sex with men (n = 26) in Malindi, Kenya, participated in individual interviews to examine sociocultural processes influencing sexual identity construction and decision-making. Four key themes were identified: (1) tensions between perceptions of 'homosexuality' versus being 'African', (2) gender-stereotyped beliefs about sexual positioning, (3) socioeconomic status and limitations to personal agency and (4) objectification and commodification of non-normative sexualities. Findings from this analysis emphasise the need to conceive of same-sex sexuality and HIV risk as context-dependent social phenomena. Multiple sociocultural axes were found to converge and shape sexual identity and sexual decision-making among this population. These axes and their interactive effects should be considered in the design of future interventions and other public health programmes for men who have sex with men in this region. PMID- 26551762 TI - The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes. AB - The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Concentrations of 6alpha-hydroxypaclitaxel and EXP-3174 were measured by high-performance liquid chromatography after incubations with paclitaxel, losartan or EXP-3174 in HLMs from seven donors with different CYP2C8 and CYP2C9 genotypes. The half maximal inhibitory concentration (IC50 ) values were not fully dependent on CYP2C8 genotypes. Although the degree of inhibition was small, losartan significantly inhibited the production of 6alpha hydroxypaclitaxel at a concentration of 1 MUmol/L in only HL20 with the CYP2C8*3/*3 genotype. HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Significant inhibition of 6alpha hydroxypaclitaxel formation by EXP-3174 could only be found at levels that were 50 times higher (100 MUmol/L) than the maximum concentration generated in the inhibition study using losartan. These results suggest that the metabolic interaction between losartan and paclitaxel is dependent on losartan itself rather than its metabolite and that the CYP2C8 inhibition by losartan is not affected by the CYP2C9 genotype. Further study is needed to define the effect of CYP2C8 genotypes on losartan-paclitaxel interaction. PMID- 26551763 TI - Protective Effect of Zingiber Officinale against CCl4-Induced Liver Fibrosis Is Mediated through Downregulating the TGF-beta1/Smad3 and NF-KB/IKB Pathways. AB - No ideal hepatoprotective agents are available in modern medicine to effectively prevent liver disorders. In this study, we aimed at evaluating the potential of Zingiber officinale in the regression of liver fibrosis and its underlining mechanism of action. To induce liver fibrosis, male Wistar rats received CCl4 (2 ml/kg/2 times/week; i.p.), with and without 300 or 600 mg/kg Z. officinale extract daily through oral gavage. To assess the protective effect of Z. officinale, liver function parameters, histopathology, inflammatory markers and gene expression of transforming growth factor-beta 1 (TGF-beta1)/Smad3 and nuclear factor-kappa B (NF-KB)/IKB pathways were analyzed. Results demonstrate that Z. officinale extract markedly prevented liver injury as evident by the decreased liver marker enzymes. Concurrent administration of Z. officinale significantly protected against the CCl4-induced inflammation as showed by the decreased pro-inflammatory cytokine levels as well as the downregulation of the NF-KB)/IKB and TGF-beta1/Smad3 pathways in CCl4-administered rats. In conclusion, our study provides evidence that the protective effect of Z. officinale against rat liver fibrosis could be explained through its ability to modulate the TGF beta1/Smad3 and NF-KB)/IKB signaling pathways. PMID- 26551764 TI - Electrical mapping in bipolar disorder patients during the oddball paradigm. AB - Bipolar disorder (BD) is characterized by an alternated occurrence between acute mania episodes and depression or remission moments. The objective of this study is to analyze the information processing changes in BP (Bipolar Patients) (euthymia, depression and mania) during the oddball paradigm, focusing on the P300 component, an electric potential of the cerebral cortex generated in response to external sensorial stimuli, which involves more complex neurophysiological processes related to stimulus interpretation. Twenty-eight bipolar disorder patients (BP) (17 women and 11 men with average age of 32.5, SD: 9.5) and eleven healthy controls (HC) (7 women and 4 men with average age of 29.78, SD: 6.89) were enrolled in this study. The bipolar patients were divided into 3 major groups (i.e., euthymic, depressive and maniac) according to the score on the Clinical Global Impression--Bipolar Version (CGI-BP). The subjects performed the oddball paradigm simultaneously to the EEG record. EEG data were also recorded before and after the execution of the task. A one-way ANOVA was applied to compare the P300 component among the groups. After observing P300 and the subcomponents P3a and P3b, a similarity of amplitude and latency between euthymic and depressive patients was observed, as well as small amplitude in the pre-frontal cortex and reduced P3a response. This can be evidence of impaired information processing, cognitive flexibility, working memory, executive functions and ability to shift the attention and processing to the target and away from distracting stimuli in BD. Such neuropsychological impairments are related to different BD symptoms, which should be known and considered, in order to develop effective clinical treatment strategies. PMID- 26551765 TI - How Patient Comments Affect Consumers' Use of Physician Performance Measures. AB - BACKGROUND: Patients' comments about doctors are increasingly available on the internet. The effects of these anecdotal accounts on consumers' engagement with reports on doctor quality, use of more statistically reliable performance measures, and ability to choose doctors wisely are unknown. OBJECTIVE: To examine the effects of providing patient comments along with standardized performance information in a web-based public report. DESIGN: Participants were randomly assigned to view 1 of 6 versions of a website presenting comparative performance information on fictitious primary care doctors. Versions varied by the combination of information types [Consumer Assessment of Healthcare Providers and Systems (CAHPS), Healthcare Effectiveness Data and Information Set (HEDIS), and patient comments] and number of doctors. PARTICIPANTS: A random sample of working age adults (N=848) from an online panel representing the noninstitutionalized population of the United States. MAIN MEASURES: Time spent and actions taken on the website, probing of standardized measures, and decision quality (chosen doctor rated highest on quantifiable metrics, chosen doctor not dominated by another choice). Secondary outcomes were perceived usefulness and trustworthiness of performance metrics and evaluations of the website. KEY RESULTS: Inclusion of patient comments increased time spent on the website by 35%-42% and actions taken (clicks) by 106%-117% compared with versions presenting only CAHPS and HEDIS measures (P<0.01). It also reduced participants' attention to standardized measures (eg, percentage of time probing HEDIS measures dropped by 67%, P<0.01). When patient comments were present, fewer participants chose the doctor scoring highest on standardized metrics (44%-49% vs. 61%-62%, P<0.01). CONCLUSIONS: Including patient comments in physician performance reports enhances consumers' engagement but reduces their attention to standardized measures and substantially increases suboptimal choices. More research is needed to explore whether integrated reporting strategies could leverage the positive effects of patient comments on consumer engagement without undermining consumers' use of other important metrics for informing choice among doctors. PMID- 26551766 TI - Application of the EVEX resource to event extraction and network construction: Shared Task entry and result analysis. AB - BACKGROUND: Modern methods for mining biomolecular interactions from literature typically make predictions based solely on the immediate textual context, in effect a single sentence. No prior work has been published on extending this context to the information automatically gathered from the whole biomedical literature. Thus, our motivation for this study is to explore whether mutually supporting evidence, aggregated across several documents can be utilized to improve the performance of the state-of-the-art event extraction systems. RESULTS: In the GE task, our re-ranking approach led to a modest performance increase and resulted in the first rank of the official Shared Task results with 50.97% F-score. Additionally, in this paper we explore and evaluate the usage of distributed vector representations for this challenge. CONCLUSIONS: For the GRN task, we were able to produce a gene regulatory network from the EVEX data, warranting the use of such generic large-scale text mining data in network biology settings. A detailed performance and error analysis provides more insight into the relatively low recall rates. PMID- 26551768 TI - Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats. AB - Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID- 26551767 TI - The role of prefrontal cortex during postural control in Parkinsonian syndromes a functional near-infrared spectroscopy study. AB - Postural instability represents a main source of disability in Parkinsonian syndromes and its pathophysiology is poorly understood. Indirect probes (i.e., mental imagery) of brain involvement support the role of prefrontal cortex as a key cortical region for postural control in older adults with and without Parkinsonian syndromes. Using functional near infrared spectroscopy (fNIRs) as a direct online cortical probe, this study aimed to compare neural activation patterns in prefrontal cortex, postural stability, and their respective interactions, in (1) patients with Parkinsonian syndromes; (2) those with mild parkinsonian signs; (3) and healthy older adults. Among 269 non-demented older adults (76.41 +/- 6.70 years, 56% women), 26 individuals presented with Parkinsonian syndromes (Unified Parkinson's disease rating scale (UPDRS): 11.08 +/- 3.60), 117 had mild parkinsonian signs (UPDRS: 3.21 +/- 2.49), and 126 individuals were included as a healthy control group. Participants were asked to stand upright and count silently for ten seconds while changes in oxygenated hemoglobin levels over prefrontal cortex were measured using fNIRs. We simultaneously evaluated postural stability with center of pressure velocity data recorded on an instrumented walkway. Compared to healthy controls and patients with mild parkinsonian signs, patients with Parkinsonian syndromes demonstrated significantly higher prefrontal oxygenation levels to maintain postural stability. The pattern of brain activation and postural control of participants with mild parkinsonian signs were similar to that of normal controls. These findings highlight the online role of the prefrontal cortex in postural control in patients with Parkinsonian syndromes and afford the opportunity to improve therapeutic options for postural instability. PMID- 26551769 TI - Stereoselective Synthesis of beta-Lactam-triflones under Catalyst-Free Conditions. AB - The first example of the synthesis of beta-lactam-triflones is described. Treatment of 2-diazo-1-aryl-2-(trifluoromethylsulfonyl)ethanones 1c-f with imines 2 under catalyst-free heating conditions provides pharmaceutically attractive multisubstituted beta-lactam-triflones 3 in good to high yields with regio- and diastereoselectivities. A successive Wolff rearrangement and Staudinger [2 + 2] cycloaddition reaction are key elements for the success of this transformation. PMID- 26551771 TI - Trichloroacetic Acid Versus Salicylic Acid in the Treatment of Acne Vulgaris in Dark-Skinned Patients. AB - BACKGROUND: Treatment options for acne include chemical peeling. Trichloroacetic acid (TCA) has been used for treating acne. The ability of TCA to diminish corneocyte cohesion and keratinocyte plugging addresses this mode of treatment. Salicylic acid is an excellent keratolytic agent. It is believed to function through solubilization of intercellular cement, thereby reducing corneocyte adhesion. OBJECTIVE: Comparing the therapeutic efficacy of TCA 25% peels with those of salicylic acid 30% in patients with acne vulgaris. MATERIALS AND METHODS: Twenty patients, Fitzpatrick skin Types III to V with facial acne, were enrolled. Twenty-five percent of TCA was applied to the right half of the face and 30% salicylic acid to the left half at 2-week interval for 2 months. RESULTS: Total improvement was more frequent with salicylic acid peeling (95%) versus (85%) with TCA. Total comedones improvement was more frequent with TCA peeling (80%) versus (70%) with salicylic acid. Improvement of inflammatory lesions was more frequent among the side treated with salicylic acid (85%) versus (80%) with TCA peeling. However, the results did not reach the statistical significance level. CONCLUSIONS: Trichloroacetic acid is more superior in treating comedonal lesions, whereas salicylic is more superior in treating inflammatory lesions, without significant different between their results. PMID- 26551770 TI - THE IMPACT OF DEPRESSION ON MATERNAL RESPONSES TO INFANT FACES IN PREGNANCY. AB - Research has suggested that prenatal depression may be associated with disrupted maternal responses to infant stimuli, with depressed pregnant women not showing the bias toward distressed infants as that observed in nondepressed pregnant women. The current study examined the effects of depression on self- reported responses to infant stimuli, in early pregnancy. Women with clinical depression (n = 38), and nondepressed women (n = 67) were recruited from a wider cognitive behavioral therapy trial. They completed Maternal Response Scales in which they were presented with images of distressed, neutral, and happy infant faces, with no time limit. The women rated their responses to these images along three dimensions--wanting to comfort, wanting to turn away, and feelings of anxiety- using Likert scales via a computerized task. There was evidence that women with depression in pregnancy showed different responses than did women without depression. Women with depression were substantially more likely to be in the highest quartile for ratings of wanting to turn away, odds (OR) ratio = 4.15, 95% confidence intervals (CIs) = 1.63-10.5, p = .003, and also were substantially less likely to be in the highest quartile for wanting to comfort a distressed infant face, OR = 0.22, 95% CIs = 0.09-0.54, p < .001. Findings are consistent with there being both a heightened avoidant and a reduced comforting response toward distressed infants in depressed pregnant women, providing some support that depression disrupts maternal preparations at a conscious level. PMID- 26551772 TI - Squamous Cell Carcinoma Arising in Hypertrophic Lichen Planus: A Review and Analysis of 38 Cases. AB - BACKGROUND: Hypertrophic lichen planus is a chronic variant of lichen planus with controversial malignant association. OBJECTIVE: To describe and analyze the relationship of squamous cell carcinoma (SCC) and hypertrophic lichen planus. MATERIALS AND METHODS: A retrospective chart review of patients with hypertrophic lichen planus and SCC was performed at the authors' institution. Thereafter, scientific databases were searched for articles reporting cases of SCC arising in hypertrophic lichen planus. Patient demographics, immune status, lichen planus features, and SCC data points were extracted for each patient and evaluated. RESULTS: Thirty-eight cases of SCC in hypertrophic lichen planus occurred in 16 women, average age: 61.4, and 22 men, average age: 51.3, after a lag time of 88 days to 40 years. Squamous cell carcinoma was uniformly located on the lower extremity. Men had larger SCC than women (p = .027) and a significantly longer lag time to SCC development (p = .002). Long lag time was associated with a smaller SCC size (p = .032). CONCLUSION: In the past, hypertrophic lichen planus and SCC have been considered isolated diseases. Based on an increasing number of cases, the association between hypertrophic lichen planus and keratinocyte malignancies warrants surveillance. PMID- 26551773 TI - Q-Switched 660-nm Versus 532-nm Nd: YAG Laser for the Treatment for Facial Lentigines in Asian Patients: A Prospective, Randomized, Double-Blinded, Split Face Comparison Pilot Study. AB - BACKGROUND: Q-switched (QS) 532-nm lasers are widely used to treat solar lentigines. OBJECTIVE: To compare the efficacy and safety of 660-nm and 532-nm QS neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers in the treatment for lentigines in Asians. MATERIALS AND METHODS: The halves of each face (randomly chosen) of 8 Korean Fitzpatrick Skin Type III-IV women with facial solar lentigines were treated with either 660-nm or 532-nm lasers. Pigmentation was measured objectively using a profilometric skin analysis tool and subjectively using the pigmentation area and severity index (PSI) score, global assessment of the aesthetic improvement scale (GAIS), and a patient satisfaction score at Weeks 4 and 8. RESULTS: Seven patients completed the study. No significant differences were found in the PSI, GAIS, patient satisfaction score, and melanin average score between the lasers. The melanin average level was significantly reduced by the 660-nm laser but not the 532-nm laser at Week 8 compared with the baseline. CONCLUSION: Both 660-nm and 532-nm QS Nd:YAG lasers effectively reduce pigmentation for up to 8 weeks with high patient satisfaction. The new 660-nm laser therefore increases the treatment options for lentigines in Asian skin. PMID- 26551774 TI - Commentary on Q-Switched 660-nm Versus 532-nm Nd: YAG Laser for the Treatment for Facial Lentigines in Asian Patients. PMID- 26551775 TI - TCRalphabeta CD19 depletion in allogeneic haematopoietic stem cell transplantation performed for Hurler syndrome. PMID- 26551776 TI - Torque teno virus in patients undergoing allogeneic hematopoietic stem cell transplantation for hematological malignancies. PMID- 26551777 TI - A prospective multicenter study of unrelated bone marrow transplants using a reduced-intensity conditioning regimen with low-dose ATG-F. PMID- 26551778 TI - T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes. AB - Unmanipulated haploidentical transplantation (Haplo-SCT) using post transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n=30) or high-risk CR (n=30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22-73 years), hematopoietic cell transplantation comorbidity index was ?3 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n=48, 80%), we found low incidences of grade 3-4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor. PMID- 26551779 TI - 'Coming of Age' of artificial intelligence: evolution of survivorship care through information technology. PMID- 26551780 TI - A risk-adapted approach to acute GVHD treatment: are we there yet? AB - Acute GVHD (aGVHD) is an immunologic complication of allogeneic hematopoietic cell transplantation (HCT) that can range from mild to life-threatening. Models to predict patients at risk of poor outcomes have been developed using both clinical and laboratory data, and the time to test these models in clinical trials has arrived. However, each modeling method has its potential advantages and limitations. In this mini-review, we summarize recent refinements to these models. We also suggest avenues for improving risk stratification through further studies of a patient's healing capacity and predisposition to endothelial damage, two factors that impact aGVHD outcomes but are absent from the current risk stratification models. PMID- 26551781 TI - Acute myeloid leukemia presenting with extensive bone marrow necrosis, leukemia cutis and testicular involvement: successful treatment with allogeneic hematopoietic stem cell transplantation. PMID- 26551782 TI - Nivolumab in a patient with refractory Hodgkin's lymphoma after allogeneic stem cell transplantation. PMID- 26551783 TI - Analytic morphomics: a novel CT imaging approach to quantify adipose tissue and muscle composition in allogeneic hematopoietic cell transplantation. PMID- 26551784 TI - Ordered Porous Pd Octahedra Covered with Monolayer Ru Atoms. AB - Monolayer Ru atoms covered highly ordered porous Pd octahedra have been synthesized via the underpotential deposition and thermodynamic control. Shape evolution from concave nanocube to octahedron with six hollow cavities was observed. Using aberration-corrected high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy, we provide quantitative evidence to prove that only a monolayer of Ru atoms was deposited on the surface of porous Pd octahedra. The as-prepared monolayer Ru atoms covered Pd nanostructures exhibited excellent catalytic property in terms of semihydrogenation of alkynes. PMID- 26551786 TI - Death from Hypothermia during a Training Course under "Extreme Conditions": Related to Two Cases. AB - Death from hypothermia following exhaustion or from various complicated pathologies is no longer a frequent cause of death among combat troops. During a training course under "extreme conditions" in the French Alps, two young African officers died. Confronted with these two clinically confirmed cases of hypothermia, the unknown anatomopathological and biological specificities associated with death from hypothermia were highlighted. In these typical and clinically confirmed cases of death from subacute exhaustion hypothermia, none of the signs revealed by the autopsy were specific. Although some recent publications have addressed the utility of postmortem biochemical markers when establishing a diagnosis, with no anamnesis, with no knowledge or analysis of the circumstances of death, and without an in situ examination of the body, it appears difficult, if not impossible, to confirm that death was caused by hypothermia. PMID- 26551785 TI - Polymorphisms in the Promoters of the MMP-2 and TIMP-2 Genes Are Associated with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population. AB - BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating stroke subtype. Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and the activities of MMPs are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). This study aimed to discuss relationship of MMP-2 and TIMP-2 to spontaneous deep ICH (SDICH) susceptibility and hematoma size. METHODS: Associations were tested by logistic regression and general linear models (GLM) where appropriate, adjusting with covariables of age, sex, hypertension, diabetes mellitus, smoking, and alcohol consumption. Association analyses were performed first by stratification of genders and then by the age of 65 years old (y/o). Elder population was defined as subjects who were older than 65 y/o. RESULTS: There were 396 SDICH patients and 376 control subjects in this study. In the elder group, rs7503607 C>A variant in TIMP-2 was associated with SDICH in male and overall patients (OR = 3.49, 95% CI 1.45 to 8.40, P = 0.005 and OR = 2.45, 95% CI 1.37 to 4.38, P = 0.003, respectively) in additive genetic model. In recessive genetic model, rs2285053 TT genotype in MMP-2 was correlated to SDICH in male patients and overall elder group (OR = 7.30, 95% CI 1.3 to 40, P = 0.02 and OR = 2.91, 95% CI 1.02 to 8.31, P = 0.046, respectively), and rs7503726 AA genotype in TIMP-2 was associated with SDICH in female patients (OR = 0.29, 95% CI 0.1 to 0.84, P = 0.02). In younger male and overall younger patients, SDICH patients who had supratentorial hemorrhage had significantly lower frequency of AA genotypes in rs7503726 than those with infratentorial hemorrhage (OR = 0.36, 95% CI 0.17 to 0.75, P = 0.006 and OR = 0.43, 95% CI 0.22 to 0.84, P = 0.014, respectively). Hemorrhage size increased by 9.7 (95% CI 2.1 to 43, P = 0.004) cm3 per minor allele (A) of the rs7503607 variant in the elder female patients and increased by 4.3 (95% CI 1.4 to 12.9, P = 0.009) cm3 per minor allele (A) in all elder patients. In younger patients, the hemorrhage size decreased by 3.3 (95% CI 1.2 to 9.5, P = 0.03) cm3 per minor allele of the s7503726 variant in the female patients. CONCLUSIONS: This study showed a significant association between the variants of MMP-2 and TIMP-2 promoters and SDICH susceptibility with significant age and gender differences. Hemorrhage location and size might be affected by TIMP-2 promoter variants in the SDICH patients. PMID- 26551787 TI - Effect of genetic and environmental factors on protein biomarkers for common non communicable disease and use of personally normalized plasma protein profiles (PNPPP). AB - OBJECTIVE: To study the impact of genetic and lifestyle factors on protein biomarkers and develop personally normalized plasma protein profiles (PNPPP) controlling for non-disease-related variance. MATERIALS AND METHODS: Proximity extension assays were used to measure 145 proteins in 632 controls and 344 cases with non-communicable diseases. RESULTS: Genetic and lifestyle factors explained 20-88% of the variation in healthy controls. Adjusting for these factors reduced the number of candidate biomarkers by 63%. CONCLUSION: PNPPP efficiently controls for non-disease-related variance, allowing both for efficient discovery of novel biomarkers and for covariate-independent linear cut-offs suitable for clinical use. PMID- 26551788 TI - Evaporation- and Solution-Process-Feasible Highly Efficient Thianthrene 9,9',10,10'-Tetraoxide-Based Thermally Activated Delayed Fluorescence Emitters with Reduced Efficiency Roll-Off. AB - Two novel evaporation- and solution-process-feasible thermally activated delayed fluorescence emitters, green-light-emission ACRDSO2 and yellow-light-emission PXZDSO2, based on a brand-new electron-acceptor moiety thianthrene-9,9',10,10' tetraoxide, are developed for organic light-emitting diodes. The solution processed devices, without any hole-transport layer, exhibit competitive performance and reduced efficiency roll-off compared with corresponding vacuum deposited devices. PMID- 26551789 TI - Consumption of garlic positively affects hedonic perception of axillary body odour. AB - Beneficial health properties of garlic, as well as its most common adverse effect - distinctive breath odour - are well-known. In contrast, analogous research on the effect of garlic on axillary odour is currently missing. Here, in three studies varying in the amount and nature of garlic provided (raw garlic in study 1 and 2, garlic capsules in study 3), we tested the effect of garlic consumption on the quality of axillary odour. A balanced within-subject experimental design was used. In total, 42 male odour donors were allocated to either a "garlic" or "non-garlic" condition, after which they wore axillary pads for 12 h to collect body odour. One week later, the conditions were reversed. Odour samples were then judged for their pleasantness, attractiveness, masculinity and intensity by 82 women. We found no significant differences in ratings of any characteristics in study 1. However, the odour of donors after an increased garlic dosage was assessed as significantly more pleasant, attractive and less intense (study 2), and more attractive and less intense in study 3. Our results indicate that garlic consumption may have positive effects on perceived body odour hedonicity, perhaps due to its health effects (e.g., antioxidant properties, antimicrobial activity). PMID- 26551790 TI - Oral versus intubated feeding and the effect on glycaemic and insulinaemic responses, gastric emptying and satiety. AB - Cephalic phase responses (CPR) are important in early initiation of digestion and maximal absorption of nutrients prior to ingestion. Bypassing CPR has been shown to have consequences on metabolic responses that may influence satiety. The aim of this study was to investigate if using gastric intubation to bypass oro pharyngeal and oesophageal exposure would reduce CPR including insulin and blood glucose and whether these impact on gastric emptying and satiety. Ten male subjects were tested on 2 occasions, 3-7 days apart after an overnight fast, in randomized order. Subjects were cannulated and intubated with a gastric tube for both tests. For test one, subjects ate 400 ml soup with a spoon and for test two the soup was infused into the stomach at an equivalent rate. Subsequently measurements of glycaemic (GR) and insulinaemic responses (IR) from cannula samples, breath samples for measurement of gastric emptying using the [(13)C] sodium acetate breath test and visual analogue scales (VAS) for satiety were taken over 180 min. There were differences in IR over the first 15 min (Oral: 169.0 +/- 22.1; Gastric 124.1 +/- 18.8; t(9) = 2.67; p = 0.028) but no difference in GR. There were differences in gastric emptying half time (Oral: 85.0 +/- 2.7; Gastric 79.4 +/- 3.3; t(9) = 2.40; p = 0.04) and ascension time (Oral: 68.2 +/- 2.2; Gastric 64.0 +/- 2.2; t(9) = 2.57; p = 0.03) with food taking longer to empty from the stomach on the Oral test day than on the Gastric test day. There was no significant difference in the satiety ratings. This study demonstrated that bypassing oro-pharyngeal and oesophageal exposure decreases the normal physiological CPR with detriment to IR and gastric emptying. PMID- 26551791 TI - Chronic exposure to carbon monoxide in two elderly patients using a kotatsu, a traditional Japanese charcoal-based heater. AB - We report on two elderly patients with cognitive impairments, for whom chronic carbon monoxide (CO) exposure was suspected based on elevated carboxyhaemoglobin levels in their serum. On their initial visits, cognitive impairment and brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of Alzheimer's-type dementia. However, after discontinuation of the use of a kotatsu, a charcoal-based heater, their serum carboxyhaemoglobin levels normalized and their physical symptoms resolved. Their cognitive function also slightly improved. The causal relationship between physical symptoms and cognitive impairment after chronic CO poisoning is uncertain; however, it is possible that chronic exposure to low CO levels exacerbated the clinical manifestation in our patients. PMID- 26551792 TI - Caregiving Factors Affecting Breastfeeding Duration Within a Neonatal Intensive Care Unit. AB - BACKGROUND: Increasingly, evidence supports oral feeding of very low birth-weight (VLBW) preterm infants exclusively at breast or with breast milk. Despite known breast milk benefits, outcomes related to exclusive breast milk provision are poor. Identifying factors that promote breast milk provision is critical. PURPOSE: Breastfeeding practices of mothers of VLBW infants admitted to neonatal intensive care unit were explored to identify factors associated with mode of feeding at discharge. METHOD: This retrospective study replicates previous work. Subjects were VLBW preterm infants consecutively admitted during a 24-month period. Primary outcomes included receiving any breast milk at discharge. Infant variables included gestational age, postmenstrual age of first direct breastfeeding, and comorbid conditions. Maternal variables included age and ethnicity. Nursing practice variables included first direct-to-breastfeeding, number of times to breast daily, and total direct-to-breastfeeding encounters 24 hours prior to discharge. RESULTS: A total of 96 VLBW infants (28.7 +/- 2.8 weeks' gestational age) met inclusion criteria. Of these, 48% received breast milk at discharge. Controlling for significant effect of length of stay, infants receiving first oral feed at breast were more likely discharged home receiving breast milk (adjusted odds ratio = 8.7; 95% confidence interval, 2.9-32.3; P < .0001). There were both an independent effect of first oral feed at breast and an interaction where infants of nonmarried women also benefited from the first oral feed at breast. IMPLICATIONS: Significant associations were found between first oral feeding at breast and infant receiving any breast milk at discharge. Targeting VLBW infants to receive first oral feeding at breast may yield the best outcome even among sickest and smallest infants. PMID- 26551793 TI - Mode of Birth Influences Preterm Infant Intestinal Colonization With Bacteroides Over the Early Neonatal Period. AB - BACKGROUND: Intestinal colonization during infancy is important to short- and long-term health outcomes. Bacteroides, an early member of the intestinal microbiome, is necessary for breaking down complex molecules within the intestine and function to assist the body's immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. PURPOSE: This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants, based on clinical factors including mode of birth, antibiotics, and nutrition. METHODS: Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real-time polymerase chain reaction. Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. RESULTS: We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via cesarean section (P < .001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. IMPLICATIONS FOR PRACTICE: These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via cesarean section aimed at overcoming delayed Bacteroides colonization. IMPLICATIONS FOR RESEARCH: Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health. PMID- 26551794 TI - Brucellosis in Sub-Saharan Africa: Current challenges for management, diagnosis and control. AB - Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed. PMID- 26551795 TI - Major Chemical Constituents of Bamboo Shoots (Phyllostachys pubescens): Qualitative and Quantitative Research. AB - Bamboo shoots are a delicacy in Asia. Two novel compounds, adenine-(1'R,2'R,3'R) cyclic butanetetraol carbonate (16) and (-)-(7R,8S)-(4-hydroxy-3 methoxyphenylglycerol 9-O-beta-D-[6-O-4-hydroxy-3-methoxybenzoyl]) glucopyranoside (20), together with 12 known nucleosides (1-12), 3 amino acids (13-15), beta-carboline (17), and 2 megastigmane glycosides (18, 19) were isolated from bamboo shoots (Phyllostachys pubescens). Their structures and absolute configurations were rigorously determined by detailed spectroscopic analysis, and the composition of carbohydrates in bamboo shoots was qualitatively detected and quantitatively analyzed with ion chromatography. A simple, rapid, sensitive, and accurate HPLC-UV analysis was built for routine edible quality control of bamboo shoots, and 12 major components of bamboo shoots were quantitatively analyzed. The major chemical constituents of bamboo shoots were determined to be carbohydrates, amino acids, and nucleotides. These findings are correctives to the usual view of bamboo shoots chemical composition, and the previous research reports about the chemical composition of bamboo shoots may have taken the aromatic amino acids and nucleotides for flavonoids and phenolic acids. PMID- 26551796 TI - Dynamic Optical Lattices of Subwavelength Spacing for Ultracold Atoms. AB - We propose a scheme for realizing lattice potentials of subwavelength spacing for ultracold atoms. It is based on spin-dependent optical lattices with a time periodic modulation. We show that the atomic motion is well described by the combined action of an effective, time-independent lattice of small spacing, together with a micromotion associated with the time modulation. A numerical simulation shows that an atomic gas can be adiabatically loaded into the effective lattice ground state, for time scales comparable to the ones required for adiabatic loading of standard optical lattices. We generalize our scheme to a two-dimensional geometry, leading to Bloch bands with nonzero Chern numbers. The realization of lattices of subwavelength spacing allows for the enhancement of energy scales, which could facilitate the achievement of strongly correlated (topological) states. PMID- 26551797 TI - Measurement-Induced Localization of an Ultracold Lattice Gas. AB - The process of measurement can modify the state of a quantum system and its subsequent evolution. Here, we demonstrate the control of quantum tunneling in an ultracold lattice gas by the measurement backaction imposed by the act of imaging the atoms, i.e., light scattering. By varying the rate of light scattering from the atomic ensemble, we show the crossover from the weak measurement regime, where position measurements have little influence on tunneling dynamics, to the strong measurement regime, where measurement-induced localization causes a large suppression of tunneling--a manifestation of the quantum Zeno effect. Our study realizes an experimental demonstration of the paradigmatic Heisenberg microscope and sheds light on the implications of measurement on the coherent evolution of a quantum system. PMID- 26551798 TI - Telecom-Wavelength Atomic Quantum Memory in Optical Fiber for Heralded Polarization Qubits. AB - Polarization-encoded photons at telecommunication wavelengths provide a compelling platform for practical realizations of photonic quantum information technologies due to the ease of performing single qubit manipulations, the availability of polarization-entangled photon-pair sources, and the possibility of leveraging existing fiber-optic links for distributing qubits over long distances. An optical quantum memory compatible with this platform could serve as a building block for these technologies. Here we present the first experimental demonstration of an atomic quantum memory that directly allows for reversible mapping of quantum states encoded in the polarization degree of freedom of a telecom-wavelength photon. We show that heralded polarization qubits at a telecom wavelength are stored and retrieved with near-unity fidelity by implementing the atomic frequency comb protocol in an ensemble of erbium atoms doped into an optical fiber. Despite remaining limitations in our proof-of-principle demonstration such as small storage efficiency and storage time, our broadband light-matter interface reveals the potential for use in future quantum information processing. PMID- 26551799 TI - Edwards Thermodynamics for a Driven Athermal System with Dry Friction. AB - We obtain, using semianalytical transfer operator techniques, the Edwards thermodynamics of a one-dimensional model of blocks connected by harmonic springs and subjected to dry friction. The theory is able to reproduce the linear divergence of the correlation length as a function of energy density observed in direct numerical simulations of the model under tapping dynamics. We further characterize analytically this divergence using a Gaussian approximation for the distribution of mechanically stable configurations, and show that it is related to the existence of a peculiar infinite temperature critical point. PMID- 26551800 TI - Scaling and Universality at Dynamical Quantum Phase Transitions. AB - Dynamical quantum phase transitions (DQPTs) at critical times appear as nonanalyticities during nonequilibrium quantum real-time evolution. Although there is evidence for a close relationship between DQPTs and equilibrium phase transitions, a major challenge is still to connect to fundamental concepts such as scaling and universality. In this work, renormalization group transformations in complex parameter space are formulated for quantum quenches in Ising models showing that the DQPTs are critical points associated with unstable fixed points of equilibrium Ising models. Therefore, these DQPTs obey scaling and universality. On the basis of numerical simulations, signatures of these DQPTs in the dynamical buildup of spin correlations are found with an associated power-law scaling determined solely by the fixed point's universality class. An outlook is given on how to explore this dynamical scaling experimentally in systems of trapped ions. PMID- 26551801 TI - Measuring Intermediate-Mass Black-Hole Binaries with Advanced Gravitational Wave Detectors. AB - We perform a systematic study to explore the accuracy with which the parameters of intermediate-mass black-hole binary systems can be measured from their gravitational wave (GW) signatures using second-generation GW detectors. We make use of the most recent reduced-order models containing inspiral, merger, and ringdown signals of aligned-spin effective-one-body waveforms to significantly speed up the calculations. We explore the phenomenology of the measurement accuracies for binaries with total masses between 50M(?) and 500M(?) and mass ratios between 0.1 and 1. We find that (i) at total masses below ~200M(?), where the signal-to-noise ratio is dominated by the inspiral portion of the signal, the chirp mass parameter can be accurately measured; (ii) at higher masses, the information content is dominated by the ringdown, and total mass is measured more accurately; (iii) the mass of the lower-mass companion is poorly estimated, especially at high total mass and more extreme mass ratios; and (iv) spin cannot be accurately measured for our injection set with nonspinning components. Most importantly, we find that for binaries with nonspinning components at all values of the mass ratio in the considered range and at a network signal-to-noise ratio of 15, analyzed with spin-aligned templates, the presence of an intermediate-mass black hole with mass >100M(?) can be confirmed with 95% confidence in any binary that includes a component with a mass of 130M(?) or greater. PMID- 26551802 TI - Precessional Instability in Binary Black Holes with Aligned Spins. AB - Binary black holes on quasicircular orbits with spins aligned with their orbital angular momentum have been test beds for analytic and numerical relativity for decades, not least because symmetry ensures that such configurations are equilibrium solutions to the spin-precession equations. In this work, we show that these solutions can be unstable when the spin of the higher-mass black hole is aligned with the orbital angular momentum and the spin of the lower-mass black hole is antialigned. Spins in these configurations are unstable to precession to large misalignment when the binary separation r is between the values r(ud+/ )=(?(chi(1))+/-?(qchi(2)))(4)(1-q)(-2)M, where M is the total mass, q=m(2)/m(1) is the mass ratio, and chi(1) (chi(2)) is the dimensionless spin of the more (less) massive black hole. This instability exists for a wide range of spin magnitudes and mass ratios and can occur in the strong-field regime near the merger. We describe the origin and nature of the instability using recently developed analytical techniques to characterize fully generic spin precession. This instability provides a channel to circumvent astrophysical spin alignment at large binary separations, allowing significant spin precession prior to merger affecting both gravitational-wave and electromagnetic signatures of stellar-mass and supermassive binary black holes. PMID- 26551803 TI - Dark Matter Ignition of Type Ia Supernovae. AB - Recent studies of low redshift type Ia supernovae (SN Ia) indicate that half explode from less than Chandrasekhar mass white dwarfs, implying ignition must proceed from something besides the canonical criticality of Chandrasekhar mass SN Ia progenitors. We show that 1-100 PeV mass asymmetric dark matter, with imminently detectable nucleon scattering interactions, can accumulate to the point of self-gravitation in a white dwarf and collapse, shedding gravitational potential energy by scattering off nuclei, thereby heating the white dwarf and igniting the flame front that precedes SN Ia. We combine data on SN Ia masses with data on the ages of SN Ia-adjacent stars. This combination reveals a 2.8sigma inverse correlation between SN Ia masses and ignition ages, which could result from increased capture of dark matter in 1.4 vs 1.1 solar mass white dwarfs. Future studies of SN Ia in galactic centers will provide additional tests of dark-matter-induced type Ia ignition. Remarkably, both bosonic and fermionic SN Ia-igniting dark matter also resolve the missing pulsar problem by forming black holes in ?10 Myr old pulsars at the center of the Milky Way. PMID- 26551804 TI - Chiral Alfven Wave in Anomalous Hydrodynamics. AB - We study the hydrodynamic regime of chiral plasmas at high temperature. We find a new type of gapless collective excitation induced by chiral effects in an external magnetic field. This is a transverse wave, and it is present even in incompressible fluids, unlike the chiral magnetic and chiral vortical waves. The velocity is proportional to the coefficient of the gravitational anomaly. We briefly discuss the possible relevance of this "chiral Alfven wave" in physical systems. PMID- 26551805 TI - Yangian Symmetry of Scattering Amplitudes and the Dilatation Operator in N=4 Supersymmetric Yang-Mills Theory. AB - It is known that the Yangian of PSU(2,2|4) is a symmetry of the tree-level S matrix of N=4 super Yang-Mills theory. On the other hand, the complete one-loop dilatation operator in the same theory commutes with the level-one Yangian generators only up to certain boundary terms found by Dolan, Nappi, and Witten. Using a result by Zwiebel, we show how the Yangian symmetry of the tree-level S matrix of N=4 super Yang-Mills theory implies precisely the Yangian invariance, up to boundary terms, of the one-loop dilatation operator. PMID- 26551808 TI - Nonperturbative Quantum Physics from Low-Order Perturbation Theory. AB - The Stark effect in hydrogen and the cubic anharmonic oscillator furnish examples of quantum systems where the perturbation results in a certain ionization probability by tunneling processes. Accordingly, the perturbed ground-state energy is shifted and broadened, thus acquiring an imaginary part which is considered to be a paradigm of nonperturbative behavior. Here we demonstrate how the low order coefficients of a divergent perturbation series can be used to obtain excellent approximations to both real and imaginary parts of the perturbed ground state eigenenergy. The key is to use analytic continuation functions with a built-in singularity structure within the complex plane of the coupling constant, which is tailored by means of Bender-Wu dispersion relations. In the examples discussed the analytic continuation functions are Gauss hypergeometric functions, which take as input fourth order perturbation theory and return excellent approximations to the complex perturbed eigenvalue. These functions are Borel consistent and dramatically outperform widely used Pade and Borel-Pade approaches, even for rather large values of the coupling constant. PMID- 26551809 TI - Ultrafast Charge Transfer of a Valence Double Hole in Glycine Driven Exclusively by Nuclear Motion. AB - We explore theoretically the ultrafast transfer of a double electron hole between the functional groups of glycine after K-shell ionization and subsequent Auger decay. Although a large energy gap of about 15 eV initially exists between the two electronic states involved and coherent electronic dynamics play no role in the hole transfer, we find that the double hole is transferred within 3 to 4 fs between both functional ends of the glycine molecule driven solely by specific nuclear displacements and non-Born-Oppenheimer effects. The nuclear displacements along specific vibrational modes are of the order of 15% of a typical chemical bond between carbon, oxygen, and nitrogen atoms and about 30% for bonds involving hydrogen atoms. The time required for the hole transfer corresponds to less than half a vibrational period of the involved nuclear modes. This finding challenges the common wisdom that nuclear dynamics of the molecular skeleton are unimportant for charge transfer processes at the few-femtosecond time scale and shows that they can even play a prominent role. It also indicates that in x-ray imaging experiments, in which ionization is unavoidable, valence electron redistribution caused by nuclear dynamics might be much faster than previously anticipated. Thus, non-Born-Oppenheimer effects may affect the apparent electron densities extracted from such measurements. PMID- 26551810 TI - Measurement of Dipole Matrix Elements with a Single Trapped Ion. AB - We demonstrate a method to determine dipole matrix elements by comparing measurements of dispersive and absorptive light ion interactions. We measure the matrix element pertaining to the Ca II H line, i.e., the 4(2)S(1/2)<->4(2)P(1/2) transition of (40)Ca(+), for which we find the value 2.8928(43) ea(0). Moreover, the method allows us to deduce the lifetime of the 4(2)P(1/2) state to be 6.904(26) ns, which is in agreement with predictions from recent theoretical calculations and resolves a long-standing discrepancy between calculated values and experimental results. PMID- 26551811 TI - Incompressible Polaritons in a Flat Band. AB - We study the interplay of geometric frustration and interactions in a nonequilibrium photonic lattice system exhibiting a polariton flat band as described by a variant of the Jaynes-Cummings-Hubbard model. We show how to engineer strong photonic correlations in such a driven, dissipative system by quenching the kinetic energy through frustration. This produces an incompressible state of photons characterized by short-ranged crystalline order with period doubling. The latter manifests itself in strong spatial correlations, i.e., on site and nearest-neighbor antibunching combined with extended density-wave oscillations at larger distances. We propose a state-of-the-art circuit QED realization of our system, which is tunable in situ. PMID- 26551806 TI - First Observation of the Hadronic Transition Upsilon(4S)->etah(b)(1P) and New Measurement of the h(b)(1P) and eta(b)(1S) Parameters. AB - Using a sample of 771.6*10(6) UpsilonUpsilon(4S) decays collected by the Belle experiment at the KEKB e(+)e(-) collider, we observe, for the first time, the transition Upsilon(4S)->etah(b)(1P) with the branching fraction B[Upsilon(4S) >etah(b)(1P)]=(2.18+/-0.11+/-0.18)*10(-3) and we measure the h(b)(1P) mass M(h(b)(1P))=(9899.3+/-0.4+/-1.0) MeV/c(2), corresponding to the hyperfine (HF) splitting DeltaM(HF)(1P)=(0.6+/-0.4+/-1.0) MeV/c(2). Using the transition h(b)(1P)->gammaeta(b)(1S), we measure the eta(b)(1S) mass M(eta(b)(1S))=(9400.7+/ 1.7+/-1.6) MeV/c(2), corresponding to DeltaM(HF)(1S)=(59.6+/-1.7+/-1.6) MeV/c(2), the eta(b)(1S) width Gamma(eta(b)(1S))=(8(-5)(+6)+/-5) MeV/c(2) and the branching fraction B[h(b)(1P)->gammaeta(b)(1S)]=(56+/-8+/-4)%. PMID- 26551813 TI - Anomalous Diffraction in Cold Magnetized Plasma. AB - Cold magnetized plasma possesses an anisotropic permittivity tensor with a unique dispersion relation that for adequate electron density and magnetic field results in anomalous diffraction of a right-hand circularly polarized beam. In this work, we demonstrate experimentally anomalous diffraction of a microwave beam in plasma. Additionally, decreasing the electron density enables observation of the transition of the material from a hyperbolic to a standard material. Manipulation of the control parameters will enable plasma to serve as a reconfigurable metamaterial-like medium. PMID- 26551812 TI - Raman-Free, Noble-Gas-Filled Photonic-Crystal Fiber Source for Ultrafast, Very Bright Twin-Beam Squeezed Vacuum. AB - We report a novel source of twin beams based on modulational instability in high pressure argon-filled hollow-core kagome-style photonic-crystal fiber. The source is Raman-free and manifests strong photon-number correlations for femtosecond pulses of squeezed vacuum with a record brightness of ~2500 photons per mode. The ultra-broadband (~50 THz) twin beams are frequency tunable and contain one spatial and less than 5 frequency modes. The presented source outperforms all previously reported squeezed-vacuum twin-beam sources in terms of brightness and low mode content. PMID- 26551814 TI - Universal Long-Range Nanometric Bending of Water by Light. AB - Resolving mechanical effects of light on fluids has fundamental importance with wide applications. Most experiments to date on optofluidic interface deformation exploited radiation forces exerted by normally incident lasers. However, the intriguing effects of photon momentum for any configuration, including the unique total internal reflection regime, where an evanescent wave leaks above the interface, remain largely unexplored. A major difficulty in resolving nanomechanical effects has been the lack of a sensitive detection technique. Here, we devise a simple setup whereby a probe laser produces high-contrast Newton-ring-like fringes from a sessile water drop. The mechanical action of the photon momentum of a pump beam modulates the fringes, thus allowing us to perform a direct noninvasive measurement of a nanometric bulge with sub-5-nm precision. Remarkably, a <10 nm difference in the height of the bulge due to different laser polarizations and nonlinear enhancement in the bulge near total internal reflection is isolated. In addition, the nanometric bulge is shown to extend far longer, 100 times beyond the pump spot. Our high precision data validate the century-old Minkowski theory for a general angle and offer potential for novel optofluidic devices and noncontact nanomanipulation strategies. PMID- 26551815 TI - Observation of Single-Mode, Kelvin-Helmholtz Instability in a Supersonic Flow. AB - We report the first observation, in a supersonic flow, of the evolution of the Kelvin-Helmholtz instability from a single-mode initial condition. To obtain these data, we used a novel experimental system to produce a steady shock wave of unprecedented duration in a laser-driven experiment. The shocked, flowing material creates a shear layer between two plasmas at high energy density. We measured the resulting interface structure using radiography. Hydrodynamic simulations reproduce the large-scale structures very well and the medium-scale structures fairly well, and imply that we observed the expected reduction in growth rate for supersonic shear flow. PMID- 26551816 TI - Quantum Oscillations without a Fermi Surface and the Anomalous de Haas-van Alphen Effect. AB - The de Haas-van Alphen effect (dHvAE), describing oscillations of the magnetization as a function of magnetic field, is commonly assumed to be a definite sign for the presence of a Fermi surface (FS). Indeed, the effect forms the basis of a well-established experimental procedure for accurately measuring FS topology and geometry of metallic systems, with parameters commonly extracted by fitting to the Lifshitz-Kosevich (LK) theory based on Fermi liquid theory. Here we show that, in contrast to this canonical situation, there can be quantum oscillations even for band insulators of certain types. We provide simple analytic formulas describing the temperature dependence of the quantum oscillations in this setting, showing strong deviations from LK theory. We draw connections to recent experiments and discuss how our results can be used in future experiments to accurately determine, e.g., hybridization gaps in heavy fermion systems. PMID- 26551817 TI - High-T(c) Superconductivity at the Interface between the CaCuO2 and SrTiO3 Insulating Oxides. AB - At interfaces between complex oxides it is possible to generate electronic systems with unusual electronic properties, which are not present in the isolated oxides. One important example is the appearance of superconductivity at the interface between insulating oxides, although, until now, with very low T(c). We report the occurrence of high T(c) superconductivity in the bilayer CaCuO(2)/SrTiO(3), where both the constituent oxides are insulating. In order to obtain a superconducting state, the CaCuO(2)/SrTiO(3) interface must be realized between the Ca plane of CaCuO(2) and the TiO(2) plane of SrTiO(3). Only in this case can oxygen ions be incorporated in the interface Ca plane, acting as apical oxygen for Cu and providing holes to the CuO(2) planes. A detailed hole doping spatial profile can be obtained by scanning transmission electron microscopy and electron-energy-loss spectroscopy at the O K edge, clearly showing that the (super)conductivity is confined to about 1-2 CaCuO(2) unit cells close to the interface with SrTiO(3). The results obtained for the CaCuO(2)/SrTiO(3) interface can be extended to multilayered high T(c) cuprates, contributing to explaining the dependence of T(c) on the number of CuO(2) planes in these systems. PMID- 26551818 TI - Ferromagnetic Spin Fluctuation and Unconventional Superconductivity in Rb2Cr3As3 Revealed by 75As NMR and NQR. AB - We report (75)As nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) studies on the superconductor Rb(2)Cr(3)As(3) with a quasi-one dimensional crystal structure. Below T~100 K, the spin-lattice relaxation rate (1/T(1)) divided by temperature, 1/T(1)T, increases upon cooling down to T(c)=4.8 K, showing a Curie-Weiss-like temperature dependence. The Knight shift also increases with decreasing temperature. These results suggest ferromagnetic spin fluctuation. In the superconducting state, 1/T(1) decreases rapidly below T(c) without a Hebel-Slichter peak, and follows a T(5) variation below T~3 K, which points to unconventional superconductivity with point nodes in the gap function. PMID- 26551819 TI - Two-Dimensional Superconductor with a Giant Rashba Effect: One-Atom-Layer Tl-Pb Compound on Si(111). AB - A one-atom-layer compound made of one monolayer of Tl and one-third monolayer of Pb on a Si(111) surface having ?3*?3 periodicity was found to exhibit a giant Rashba-type spin splitting of metallic surface-state bands together with two dimensional superconducting transport properties. Temperature-dependent angle resolved photoelectron spectroscopy revealed an enhanced electron-phonon coupling for one of the spin-split bands. In situ micro-four-point-probe conductivity measurements with and without magnetic field demonstrated that the (Tl, Pb)/Si(111) system transformed into the superconducting state at 2.25 K, followed by the Berezinskii-Kosterlitz-Thouless mechanism. The 2D Tl-Pb compound on Si(111) is believed to be the prototypical object for prospective studies of intriguing properties of the superconducting 2D system with lifted spin degeneracy, bearing in mind that its composition, atomic and electron band structures, and spin texture are already well established. PMID- 26551820 TI - Topological Magnon Bands in a Kagome Lattice Ferromagnet. AB - There is great interest in finding materials possessing quasiparticles with topological properties. Such materials may have novel excitations that exist on their boundaries which are protected against disorder. We report experimental evidence that magnons in an insulating kagome ferromagnet can have a topological band structure. Our neutron scattering measurements further reveal that one of the bands is flat due to the unique geometry of the kagome lattice. Spin wave calculations show that the measured band structure follows from a simple Heisenberg Hamiltonian with a Dzyaloshinkii-Moriya interaction. This serves as the first realization of an effectively two-dimensional topological magnon insulator--a new class of magnetic material that should display both a magnon Hall effect and protected chiral edge modes. PMID- 26551821 TI - Disorder-Driven Spin-Orbital Liquid Behavior in the Ba3XSb2O9 Materials. AB - Recent experiments on the Ba(3)XSb(2)O(9) family have revealed materials that potentially realize spin- and spin-orbital liquid physics. However, the lattice structure of these materials is complicated due to the presence of charged X(2+) Sb(5+) dumbbells, with two possible orientations. To model the lattice structure, we consider a frustrated model of charged dumbbells on the triangular lattice, with long-range Coulomb interactions. We study this model using Monte Carlo simulation, and find a freezing temperature, T(frz), at which the simulated structure factor matches well to low-temperature x-ray diffraction data for Ba(3)CuSb(2)O(9). At T=T(frz) we find a complicated "branching" structure of superexchange-linked X(2+) clusters, which form a fractal pattern with fractal dimension d(f)=1.90. We show that this gives a natural explanation for the presence of orphan spins. Finally we provide a plausible mechanism by which such dumbbell disorder can promote a spin-orbital resonant state with delocalized orphan spins. PMID- 26551822 TI - Ultrafast Nonlinear Response of Bulk Plasmons in Highly Doped ZnO Layers. AB - Longitudinal bulk plasmons in an n-doped ZnO layer system are studied by two color femtosecond pump-probe spectroscopy in the midinfrared. The optical bulk plasmon resonance identified in linear reflectivity spectra undergoes a strong redshift and a limited broadening upon intraband excitation of electrons. The nonlinear changes of plasmon absorption decay on a time scale of 2 ps and originate from the intraband redistribution of electrons. Theoretical calculations explain the plasmon redshift by the transient increase of the ensemble-averaged electron mass and the concomitantly reduced plasma frequency in the hot electron plasma. The observed bulk plasmon nonlinearity holds strong potential for applications in plasmonics. PMID- 26551824 TI - Entropy-Driven Chiral Order in a System of Achiral Bent Particles. AB - Why should achiral particles organize into a helical structure? Here, using theory and molecular dynamics simulations we show that at high concentration crescent-shaped particles interacting through a purely repulsive potential form the twist-bend nematic phase, which features helical order of the twofold symmetry axes of particles, with doubly degenerate handedness. Spontaneous breaking of the chiral symmetry is driven by the entropic gain that derives from the decrease in excluded volume in the helical arrangement. Crucial to this purpose is the concave shape of particles. This study is based on a general formulation of the Onsager theory, which includes biaxiality and polarity of phase and particles, in addition to the space modulation of order. Molecular dynamics simulations corroborate the theoretical predictions and provide further insights into the structure of the helical phase. PMID- 26551823 TI - Gigahertz Dielectric Polarization of Substitutional Single Niobium Atoms in Defective Graphitic Layers. AB - We synthesize two Nb/C composites with an order of magnitude difference in the density of single niobium atoms substituted into defective graphitic layers. The concentration and sites of single Nb atoms are identified using aberration corrected scanning transmission electron microscopy and density functional theory. Comparing the experimental complex permittivity spectra reveals that a representative dielectric resonance at ~16 GHz originates from the intrinsic polarization of single Nb atom sites, which is confirmed by theoretical simulations. The single-atom dielectric resonance represents the physical limit of the electromagnetic response of condensed matter, and thus might open up a new avenue for designing electromagnetic wave absorption materials. Single-atom resonance also has important implications in understanding the correlation between the macroscopic dielectric behaviors and the atomic-scale structural origin. PMID- 26551825 TI - Lagrangian Descriptors of Thermalized Transition States on Time-Varying Energy Surfaces. AB - Thermalized chemical reactions driven under dynamical load are characteristic of activated dynamics for arbitrary nonautonomous systems. Recent generalizations of transition state theory to obtain formally exact rates have required the construction of a time-dependent transition state trajectory. Here, we show that Lagrangian descriptors can be used to obtain this structure directly. By developing a phase space separatrix that is void of recrossings, these constructs allow for the principal criterion in the implementation of modern rate theories to be satisfied. Thus, the reactive flux over a time-varying barrier can be determined without ambiguity in chemical reactions. The generality of the formalism suggests that this approach is applicable to any activated system subjected to arbitrary driving and thermal fluctuations. PMID- 26551826 TI - Sensing Polymer Chain Dynamics through Ring Topology: A Neutron Spin Echo Study. AB - Using neutron spin echo spectroscopy, we show that the segmental dynamics of polymer rings immersed in linear chains is completely controlled by the host. This transforms rings into ideal probes for studying the entanglement dynamics of the embedding matrix. As a consequence of the unique ring topology, in long chain matrices the entanglement spacing is directly revealed, unaffected by local reptation of the host molecules beyond this distance. In shorter entangled matrices, where in the time frame of the experiment secondary effects such as contour length fluctuations or constraint release could play a role, the ring motion reveals that the contour length fluctuation is weaker than assumed in state-of-the-art rheology and that the constraint release is negligible. We expect that rings, as topological probes, will also grant direct access to molecular aspects of polymer motion which have been inaccessible until now within chains adhering to more complex architectures. PMID- 26551827 TI - Theory of the Sea Ice Thickness Distribution. AB - We use concepts from statistical physics to transform the original evolution equation for the sea ice thickness distribution g(h) from Thorndike et al. into a Fokker-Planck-like conservation law. The steady solution is g(h)=N(q)h(q)e(-h/H), where q and H are expressible in terms of moments over the transition probabilities between thickness categories. The solution exhibits the functional form used in observational fits and shows that for h?1, g(h) is controlled by both thermodynamics and mechanics, whereas for h?1 only mechanics controls g(h). Finally, we derive the underlying Langevin equation governing the dynamics of the ice thickness h, from which we predict the observed g(h). The genericity of our approach provides a framework for studying the geophysical-scale structure of the ice pack using methods of broad relevance in statistical mechanics. PMID- 26551828 TI - Comment on "Interplay between Water and TiO2 Anatase (101) Surface with Subsurface Oxygen Vacancy". PMID- 26551829 TI - Comment on "Boson Peak in Deeply Cooled Confined Water: A Possible Way to Explore the Existence of the Liquid-to-Liquid Transition in Water". PMID- 26551830 TI - Wang et al. Reply. PMID- 26551831 TI - Erratum: Fabry-Perot Interferometer with Quantum Mirrors: Nonlinear Light Transport and Rectification [Phys. Rev. Lett. 113, 243601 (2014)]. PMID- 26551832 TI - Erratum: Asymptotic Scaling Behavior of Self-Avoiding Walks on Critical Percolation Clusters [Phys. Rev. Lett. 113, 255701 (2014)]. PMID- 26551833 TI - Multiple eruptive milia on scalp. PMID- 26551834 TI - Overview: A New Era of Cancer Genomics in Lymphoid Malignancies. AB - Novel technologies including next-generation sequencing have not only delineated the molecular pathogenesis of lymphoid malignancies but also identified novel biomarkers predicting the outcome of specific therapies. In addition, many actionable genetic alterations, which can be targeted by either specific therapeutic compounds or monoclonal antibodies, have been discovered. An appropriate selection of the patients enrolled in clinical trials using novel drugs targeting specific mutations will usher in a new era of personalized medicine in clinical practice of lymphoid malignancies. PMID- 26551835 TI - Three Residues Make an Evolutionary Switch for Folding and RNA-Destabilizing Activity in the TTP Family of Proteins. AB - Tristetraprolin (TTP) binds to mRNA transcripts to promote their degradation. The TTP protein family in humans includes two other proteins, TIS11b and TIS11d. All three proteins contain a highly homologous RNA binding domain (RBD) that consists of two CCCH zinc fingers (ZFs). Both ZFs are folded in the absence of RNA in TIS11d and TIS11b. In TTP, however, only ZF1 adopts a stable fold. The focus of this study is to understand the origin and biological significance of the structural differences of the RBD. We identified three residues that affect the affinity for the structural Zn(2+) and determine the folding of ZF2 in the absence of RNA. We observed that the mRNA destabilizing activity of TTP was increased when the partially disordered RBD of TTP was replaced with the fully structured RBD of TIS11d, indicating that differences in the folded state of the RBD affect the activity of the proteins in the cell. PMID- 26551807 TI - Measurements of Elliptic and Triangular Flow in High-Multiplicity 3He+Au Collisions at ?(s(NN))=200 GeV. AB - We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity (3)He+Au collisions at ?(s(NN))=200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in (3)He+Au and in p+p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the (3)He+Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d+Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three (3)He nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems. PMID- 26551837 TI - A Glimpse of Microbial Power in Preventive Medicine. PMID- 26551836 TI - Mass Spectrometric Analysis of Surface-Exposed Regions in the Hexadecameric Phosphorylase Kinase Complex. AB - Phosphorylase kinase (PhK) is a 1.3 MDa (alphabetagammadelta)4 enzyme complex, in which alphabetagammadelta protomers associate in D2 symmetry to form two large octameric lobes that are interconnected by four bridges. The approximate locations of the subunits have been mapped in low-resolution cryo-electron microscopy structures of the complex; however, the disposition of the subunits within the complex remains largely unknown. We have used partial proteolysis and chemical footprinting in combination with high-resolution mass spectrometry to identify surface-exposed regions of the intact nonactivated and phospho-activated conformers. In addition to the known interaction of the gamma subunit's C terminal regulatory domain with the delta subunit (calmodulin), our exposure results indicate that the catalytic core of gamma may also anchor to the PhK complex at the bottom backside of its C-terminal lobe facing away from the active site cleft. Exposed loops on the alpha and beta regulatory subunits within the complex occur at regions overlapping with tissue-specific alternative RNA splice sites and regulatory phosphorylatable domains. Their phosphorylation alters the surface exposure of alpha and beta, corroborating previous biophysical and biochemical studies that detected phosphorylation-dependent conformational changes in these subunits; however, for the first time, specific affected regions have been identified. PMID- 26551838 TI - Early invasive fungal infections and colonization in patients with cirrhosis admitted to the intensive care unit. AB - Bacterial infections in cirrhosis are common and associated with increased mortality, but little is known about fungal infections. The aim of this study, a sub-analysis of the Fungal Infection Risk Evaluation study, was to assess the incidence and implications of early invasive fungal disease (IFD) in patients with cirrhosis admitted to intensive care units (ICU). Clinical and laboratory parameters collected in the first 3 days of ICU stay for 782 patients with cirrhosis and/or portal hypertension were analysed and compared with those of 273 patients with very severe cardiovascular disease (CVD). The CVD patients had more co-morbidities and higher APACHE II scores. The overall incidence of IFD was similar in the two groups, but the incidence of IFD in ICU was higher in liver patients (1% versus 0.4%; p 0.025) as was fungal colonization (23.8% versus 13.9%; p 0.001). The ICU and in-hospital mortality, and length of stay were similar in the two groups. A higher proportion of liver patients received antifungal therapy (19.2% versus 7%; p <0.0005). There was no difference in mortality between colonized patients who received antifungal therapy and colonized patients who did not. The incidence of IFD in patients with cirrhosis in ICU is higher compared with another high-risk group, although it is still very low. This risk might be higher in patients with advanced liver disease admitted with acute-on-chronic liver failure, and this should be investigated further. Our data do not support prophylactic use of antifungal therapy in cirrhosis. PMID- 26551840 TI - Characterization of an emergent clone of enteroinvasive Escherichia coli circulating in Europe. AB - Enteroinvasive Escherichia coli (EIEC) cause intestinal illness indistinguishable from that caused by Shigella, mainly in developing countries. Recently an upsurge of cases of EIEC infections has been observed in Europe, with two large outbreaks occurring in Italy and in the United Kingdom. We have characterized phenotypically and genotypically the strains responsible for these epidemics together with an additional isolate from a sporadic case isolated in Spain. The three isolates belonged to the same rare serotype O96:H19 and were of sequence type ST-99, never reported before in EIEC or Shigella. The EIEC strains investigated possessed all the virulence genes harboured on the large plasmid conferring the invasive phenotype to EIEC and Shigella while showing only some of the known chromosomal virulence genes and none of the described pathoadaptative mutations. At the same time, they displayed motility abilities and biochemical requirements resembling more closely those of the non-pathogenic E. coli rather than the EIEC and Shigella strains used as reference. Our observations suggested that the O96:H19 strains belong to an emerging EIEC clone, which could be the result of a recent event of acquisition of the invasion plasmid by commensal E. coli. PMID- 26551841 TI - Infections related to Actinotignum schaalii (formerly Actinobaculum schaalii): a 3-year prospective observational study on 50 cases. PMID- 26551842 TI - Correlation between body mass index and faecal microbiota from children. AB - Childhood obesity is an increasing problem at the global level and considered as a risk factor for obesity development and the associated co-morbidities in adult life. In this study, the occurrence of Bacteroides fragilis group, Clostridium spp., Bifidobacterium spp. and Escherichia coli in 84 faecal samples from 30 obese, 24 overweight and 30 lean children was verified by culture technique and quantitative determination by quantitative PCR. In addition, Lactobacillus spp. and Methanobrevibacter smithii were also analysed. A correlation between the body mass index (BMI) and these bacteria was sought. Bacteroides vulgatus, Clostridium perfringens and Bifidobacterium adolescentis were most prevalent in all samples evaluated by culture-method. The B. fragilis group were found at high concentrations in obese and overweight children when compared with the lean ones (p 0.015). The obese and overweight children harboured higher numbers of Lactobacillus spp. than lean children (p 0.022). The faecal concentrations of the B. fragilis group (r = 0.24; p 0.026) and Lactobacillus spp. (r = 0.44; p 0.002) were positively correlated with BMI. Bifidobacterium spp. were found in higher numbers in the lean group than the overweight and obese ones (p 0.042). Furthermore, a negative correlation between BMI and Bifidobacterium spp. copy number (r = -0.22; p 0.039) was observed. Our findings show some difference in the intestinal microbial ecosystem of obese children compared with the lean ones and a significant association between number of Lactobacillus spp. and B. fragilis group and BMI. PMID- 26551839 TI - Increased risk of virologic failure to the first antiretroviral regimen in HIV infected migrants compared to natives: data from the ICONA cohort. AB - Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004-2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) >200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL >200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67-0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8-8.5) in migrants and 2.7 in natives (95% CI 2.2-3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25-2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01-1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor-based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives. PMID- 26551843 TI - CMI editorial report, 2016. PMID- 26551844 TI - Seroprevalence of Toscana virus in dogs from Kabylia (Algeria). PMID- 26551845 TI - [Which Factors Affect Out-of-pocket Payments for Health Care Services Among Elderly Germans? Results of a Longitudinal Study]. AB - Background: In Germany, out-of-pocket payments (OOPP) account for a large proportion of total health expenditure. However, there are only few investigations on how morbidity-related, sociodemographic and lifestyle factors affect OOPP particularly in the older population. The aim of this study was to identify factors affecting OOPP for health care services among elderly Germans in a longitudinal setting. Methods: This longitudinal study used data from 2 follow up waves (3-year interval) from a population-based prospective cohort study (ESTHER study) collected in Saarland, Germany. At the first follow-up wave, subjects were between 57 and 84 years old. Participants provided comprehensive data including individual OOPP for the preceding 3 months. Fixed effects (FE) regressions were used to determine factors affecting OOPP. Results: Mean individual OOPP (3-month period) rose from ? 119 (first wave) to ? 136 (second wave). Longitudinal regressions showed that higher morbidity did not affect OOPP. Moreover, changes in sociodemographic as well as lifestyle factors were not related to changes in OOPP. Solely, exemption of OOPP reduced the dependent variable significantly. Conclusion: In contrast to cross-sectional findings for Germany, OOPP are not related to morbidity and income in this study. This underlines the complex nature of OOPP in old age and the need for longitudinal studies to gain some insight into the underlying causal factors. PMID- 26551846 TI - [Delegation of Medical Treatment to Non-physician Health Care Professionals: The Medical Care Structure agneszwei in Brandenburg - A Qualitative Acceptance Analysis]. AB - Backround: To address the increasing shortage of primary care physicians in rural regions, pilot model projects were tested, where general practitioners delegate certain physician tasks including house calls to qualified physician assistants. Evaluations show a high level of acceptance among participating physicians, medical assistants and patients. This study aims to measure the quality of cooperation among professionals participating in an outpatient health care delegation structure agneszwei with a focus on case management in Brandenburg. Methods: We conducted 10 qualitative semi-structured expert interviews among 6 physicians and 4 physician's assistants. Results: Physicians and physicians' assistants reported the cooperative action to be successful and as an advantage for patients. The precondition for successful cooperation is that non-physician health care professionals strictly respect the governance of the General Practitioners. Physicians report that the delegation of certain medical tasks reduces their everyday workload. Physician assistants derive professional satisfaction from the confidential relationship they have with the patients. All physician assistants are in favor of medical tasks being delegated to them in regular medical outpatient care, while most physicians are skeptical or reluctant despite their reported positive experience. Conclusion: Despite the high level of acceptance of delegating some medical tasks to physician assistants, the negotiation process of introducing cooperative working structures in the outpatient health care system is still at the beginning. PMID- 26551848 TI - [Evaluation of the Activities of Community Pharmacies during the Annual Campaign with Focus on Diabetes Prevention]. AB - With its increasing incidence, diabetes is one of the major challenges of the 21th century. Against this background, the Bavarian State Ministry of Public Health and Care Services (BStMGP) started in 2014 the campaign "Diabetes moves us!". The scientific institute for prevention in health care (WIPIG) supported the activities of Bavarian pharmacies and evaluated the extent to which they might be able to contribute towards prevention. Besides additional training of pharmaceutical staff, WIPIG initiated a diabetes prevention network. Pharmacies that were members of the network had the opportunity to order a campaign package including an evaluation questionnaire and to register their activity in the calendar of events of the campaign. A total of 215 pharmacies signed up for the diabetes prevention network and registered 103 events. The WIPIG received 67 completed evaluation questionnaires. Most often (86.6%) the pharmacies conducted a blood glucose screening; 76.1% carried out screening with the diabetes risk questionnaire FINDRISC of the German Diabetes Foundation and 22.4% gave a information lecture on diabetes. During the screening 2,502 persons had their blood sugar checked and 1,765 persons filled in the FINDRISC questionnaire. Overall, 190 persons were advised to visit their physician because of a very high blood glucose level. On the basis of the FINDRISC, 80.2% were advised to change their lifestyle to prevent type 2 diabetes. PMID- 26551847 TI - [Return to Work After Shoulder Arthroscopy as an Index of Cost Effectiveness]. AB - Cost-effectiveness of shoulder arthroscopy was analyzed and assessed by the days off work as part of the indirect costs. We retrospectively evaluated a group of 266 inpatients on sick leave after arthroscopic shoulder surgery. Mean duration till return to full duty was 9.5 days, the mean sick leave benefit was ? 485. There was a statistically significant difference in the mean time to return to work between the older (age >50) and the younger group (age under 50). Secondary data analysis of sick leave and sickness benefits as indirect costs of medical treatment seems to be well suited to provide essentiell information to health care policy makers and those charged with distributing disability funds. PMID- 26551849 TI - [The Role of Psychological and Technology-related Personality Traits and Knowledge Levels as Factors Influencing Adoption of Telemonitoring by Medical Professionals]. AB - OBJECTIVES: Information and communication technologies are becoming increasingly important in health care. Randomized clinical trials have shown that telemonitoring in particular leads to improved quality of care as well as shortened hospital stays and reduced health care costs. For its long-term anchoring in medical care, user-oriented technology needs to be developed, taking into account the complex structures of technology acceptance METHODS:: Knowledge of and attitudes towards telemonitoring amongst medical professionals were investigated using an online-based approach with a random sample of n=614; the response rate was 21% (n=133). The emergence of positive attitude patterns towards telemonitoring was analyzed using the relationships between psychological and technology-related personality traits, and perceived knowledge was determined using a regression model. RESULTS: Positive attitudes towards telemonitoring are significantly influenced by the individual's knowledge and agreeableness, which is strongly characterized by altruistic traits and interpersonal trust. There is a strong association with an improvement in the quality of care, while there are differences in attitudes towards telemonitoring between health care sectors and gender. Overall, only 57% of the physicians surveyed feel sufficiently informed about the use of telemonitoring. CONCLUSION: Medical evidence is crucial for the further development of telemedicine in general and telemonitoring in particular. Improvements need to be made in knowledge transfer, the exchange of best practice solutions and the anchoring of telemedicine in education and training. PMID- 26551850 TI - [Validation of SHI Claims Data Exemplified by Gender-specific Diagnoses]. AB - Aim: Use of statutory health insurance (SHI) data in health services research is increasing steadily and questions of validity are gaining importance. Using gender-specific diagnosis as an example, the aim of this study was to estimate the prevalence of implausible diagnosis and demonstrate an internal validation strategy. Method: The analysis is based on the SHI data from Baden-Wurttemberg for 2012. Subject of validation are gender-specific outpatient diagnoses that mismatch with the gender of the insured. To uncover this implausibility, it is necessary to clarify whether the diagnosis or the gender is wrong. The validation criteria used were the presence of further gender-specific diagnoses, the presence of gender-specific settlement items, the specialization of the physician in charge and the gender assignment of the first name of the insured. To review the quality of the validation, it was verified if the gender was changed during the following year. Results: Around 5.1% of all diagnoses were gender-specific and there was a mismatch between diagnosis and gender in 0.04% of these cases. All validation criteria were useful to sort out implausibility, whereas the last one was the most effective. Only 14% remained unsolved. From the total of 1 145 insured with implausible gender-specific diagnoses, one year later 128 had a new gender (in the data). 119 of these cases were rightly classified as insured with wrong gender and 9 cases were in the unsolved group. This confirms that the validation works well. Conclusion: Implausibility in SHI data is relatively small and can be solved with appropriate validation criteria. When validating SHI data, it is advisable to question all data used critically, to use multiple validation criteria instead of just one and to abandon the idea that reality and the associated data conform to standardized norms. Keeping these aspects in mind, analysis of SHI data is a good starting point for research in health services. PMID- 26551851 TI - [Advising Women to Avoid Excessive Gestational Weight Gain: What do Pregnant Women Think?] AB - Gestational weight gain above the IOM recommendations is a risk factor for both pregnancy complications and maternal and childhood overweight. Therefore, pregnant women should be advised about their weight gain. Do these women have special specific needs? A total of 34 pregnant women were interviewed. Using Mayring's frequency analysis, we found that these pregnant women were not aware of health consequences of excessive weight gain. Furthermore, we identified 4 main types of nutritional behavior: (i) women who are informed but do not put into practice their knowledge, (ii) women who adhere strictly to recommendations, (iii) women who are led by their physical feelings and (iv) women mostly indifferent. Women who were physically inactive before pregnancy did not start exercising in pregnancy. There are still information gaps on weight gain and healthy eating that have to be considered for future interventions. According to women's behavioral patterns, interventions might yield varying results. According to women's type of behavior, interventions might yield different success rates. Motivation and providing information on suitable exercise forms during pregnancy are challenging. PMID- 26551852 TI - ['NischE - Nicht von schlechten Eltern' - Evaluation of a Multidisciplinary Teamwork Approach to Support Children in Families with Mentally Ill Parents]. AB - Objective: Evaluation of a project offering low-threshold anonymous counseling services jointly by mental health services and child and youth services to support children in families with mentally ill parents Methods: Evaluating performance data and completed questionnaires returned by parents included in the project. Results: Between 2011-2014, 150 families received up to 10 sessions of family-oriented counseling. The survey results indicate a high level of satisfaction with the services of the cooperation project. The vast majority of respondents said that they would recommend this service to others or would themselves take advantage of the services again. Conclusion: A collaboration of service providers from psychiatry and child and youth welfare department resulting in continuous availability of counseling with a common family medical perspective represents a forward-looking model for families with a mentally ill parent. PMID- 26551853 TI - ["I cannot kiss my wife"- An Analysis of Daily Experiences of MRSA-carriers]. AB - Objectives: There are no data available on the quality of care after discharge from hospital and only limited data are available on the psychosocial effects of being an MRSA carrier within the German health system. Methods: Patients who tested positive for MRSA in the previous year were invited to take part in focus groups. Results: 2 focus groups with a total of 9 MRSA-carriers were conducted. The level of knowledge about MRSA differed between participants. In some cases, lack of information led to uncertainty and inappropriate measures to counteract MRSA. Some participants restricted their social contacts, especially to children, in order to prevent transmission. Patients experienced stigmatization in the health care system more often in inpatient care than in the outpatient sector. Only in a few cases both eradication therapy and swabs for control purposes were carried out. Conclusions: Information about the appropriate treatment and management of MRSA should be made available to patients more easily; in particular, patients need to be informed that MRSA is no threat to healthy individuals. Despite the desire of MRSA-carriers to become MRSA negative, treatment and control of MRSA seem to have low priority in the ambulant health care sector in Germany. PMID- 26551854 TI - ["Pflegestutzpunkte": Care Support Centers in Germany. Where are We Heading? Results of the Evaluation of all 48 Care Support Centers in Baden-Wurttemberg]. AB - "Pflegestutzpunkte", care support centers in Germany. Where are we heading? Results of the evaluation of all 48 care support centers in Baden-Wurttemberg. Objectives: The quantitative part of the study was based on an analysis of the structures and concepts as well as the type of services and demand for counseling services for elderly and vulnerable people of all 48 care support centers in Baden-Wurttemberg. The qualitative part included interviews of employees of the care support centers on the underlying concepts of their organization. Objectives: The counseling infrastructure for elderly and vulnerable people needs to be improved in terms of transparency, networking and coordination of its services. According to the German Care Reform, care support centers, known as "Pflegestutzpunkte," should solve this problem by placing all relevant counseling services under one roof. The objective of this study was to distinguish between the various care models of care support centers currently in existence and to investigate how different models meet legal requirements. Results and Conclusions: An evaluation of the interviews and surveys shows that not all legal requirements are met. The 4 main models of care support centers vary widely and are partially incomprehensible. It also remains unclear what role the care support centers play in counseling by health and nursing insurances. These needs for further development should be kept in mind in the planned expansion of care support centers. PMID- 26551855 TI - [Choice of Hospital for Childbirth in Switzerland: Decision Factors and Sources of Information]. AB - The introduction of Swiss DRG in 2012 offers women in Switzerland free choice of hospital. The objective of this study was to identify decision factors affecting the choice of hospital birth in Switzerland and to rate the degree of utilization of information sources. In seven Swiss hospitals, located in the German-speaking part of Switzerland, women in childbed were interviewed in writing. When choosing a hospital, factors rated by women as important were professional competence, good medical care, good obstetric competence, good nursing care and a neat and clean atmosphere. Important sources of information are recommendations of friends, own experience gained during previous hospital stays, the specialist, family, and the hospital homepage. Information meetings for pregnant women are essential for hospitals because they encourage women's decision to use the hospital. Web presence of the hospital and a good relationship with the specialists or family doctors are important, but experience of friends, family or one's own experience with stay at the hospital play a more important role. PMID- 26551856 TI - ["Mental Health in Adults with Intellectual Disabilities. Protective and Risk Factors for Depression and Anxiety" - a Cross-sectional Study]. AB - Background: There are not many studies investigating mental health of individuals with intellectual disability. The aim of this study is to provide data on depression and anxiety in individuals with intellectual disability. Method: In a cross-sectional study, we assessed women and men with intellectual disability (18 65 years) with a standardized instrument with 2 divisions (division 1: variables "residence", "self-determination capabilities", "violence experiences", division 2: variables "depression" and "anxiety" with the Patient Health Questionaire-4). Univariate and bivariate analysis of the data was performed. Result: Out of a total of 59% men and 41% women, 44 participated in the study (response rate=45%). Overall, 20% (n=9) of the participants had an increased PHQ-2 score. This can be used as an indicator for depression. 18% (n=8) of the subject group indicated an increased GAD-2 score. This can be used as an indicator of anxiety. Risk factors for depressive disorders were "an increased level of disability" (RR=11,8), "living with parents" (RR=6, 7), "limited self-determination capabilities"(RR=6,2) and "fear of new situations" (RR=5:0). Violence experiences were a risk factor (RR=13,3) for anxiety. Conclusion: In view of the special methodological challenges of this study, the target group is very small. Nevertheless, this is one of the first studies in Germany that reveals factors with an impact on the mental health of individuals with intellectual disabilities. The association of experience of violence with anxiety in individuals with intellectual disability represents an important challenge for public health. PMID- 26551857 TI - Radial Versus Femoral Access in Invasively Managed Patients With Acute Coronary Syndrome: A Systematic Review and Meta-analysis. AB - BACKGROUND: Studies in patients with acute coronary syndrome (ACS) undergoing invasive management showed conflicting conclusions regarding the effect of access site on outcomes. PURPOSE: To summarize evidence from recent, high-quality trials that compared clinical outcomes occurring with radial versus femoral access in invasively managed adults with ACS. DATA SOURCES: English-language publications in MEDLINE, EMBASE, and Cochrane databases between January 1990 and August 2015. STUDY SELECTION: Randomized trials of radial versus femoral access in invasively managed patients with ACS. DATA EXTRACTION: Two investigators independently extracted the study data and rated the risk of bias. DATA SYNTHESIS: Of 17 identified randomized trials, 4 were high-quality multicenter trials that involved a total of 17 133 patients. Pooled data from the 4 trials showed that radial access reduced death (relative risk [RR], 0.73 [95% CI, 0.59 to 0.90]; P = 0.003), major adverse cardiovascular events (RR, 0.86 [CI, 0.75 to 0.98]; P = 0.025), and major bleeding (RR, 0.57 [CI, 0.37 to 0.88]; P = 0.011). Radial procedures lasted slightly longer (standardized mean difference, 0.11 minutes) and had higher risk for access-site crossover (6.3% vs. 1.7%) than did femoral procedures. LIMITATION: Heterogeneity in outcomes definitions and potential treatment modifiers across studies, including operator experience in radial procedures and concurrent anticoagulant regimens. CONCLUSION: Compared with femoral access, radial access reduces mortality, major adverse cardiovascular events, and major bleeding in patients with ACS undergoing invasive management. PRIMARY FUNDING SOURCE: None. (PROSPERO registration number: CRD42015022031). PMID- 26551858 TI - Impaired Eukaryotic Elongation Factor 1A Expression in Alzheimer's Disease. AB - BACKGROUND/AIMS: Recent studies have indicated a link between the impaired capacity of de novo protein synthesis and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, it has been established that eukaryotic elongation factor 1A (eEF1A) plays a critical role in maintaining long-term synaptic plasticity, a cellular model for learning and memory. The aim of the present study is to determine whether brain eEF1A protein levels are dysregulated in brain tissue from AD patients compared with controls. METHODS: Postmortem human brain samples collected from patients clinically diagnosed as AD, and from age-matched healthy controls, were utilized for this study. Both Western blot and immunohistochemistry approaches were utilized to investigate the potential alteration of eEF1A protein levels by using a specific antibody. RESULTS: Our data demonstrate that eEF1A expression is reduced in AD patients in the hippocampus, but not in the cerebellum or midfrontal gyrus. Furthermore, immunohistochemical experiments reveal that neuronal eEF1A reduction in the AD hippocampus is localized to the CA1 and dentate gyrus, but not to the CA3. CONCLUSION: Dysregulation of eEF1A and its associated signaling pathways might represent novel molecular mechanisms underlying AD pathogenesis. Further investigation is necessary to determine whether eEF1A is a viable therapeutic target for AD and other cognitive syndromes. PMID- 26551859 TI - Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells. AB - Pterostilbene (PT), an analog of resveratrol, exerts a potent anti-inflammatory effect. However, the protective effects of PT against inflammation in endothelial cells have not been elucidated. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of endothelial cell inflammation. In this study, we explored the effect of PT on the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs) and elaborated the role of ERS in this process. TNF-alpha treatment significantly upregulated the levels of inflammation-related molecules in cell culture media, increased the adhesion of monocytes to HUVECs, and enhanced the expression of the MMP9 and ICAM proteins in HUVECs. Additionally, TNF-alpha potently increased ERS-related protein levels, such as GRP78 and p-eIF2alpha. However, PT treatment reversed the increased production of inflammatory cytokines and the adhesion of monocytes to HUVECs, as well as reduced the TNF-alpha-induced effects exerted by ERS-related molecules. Furthermore, thapsigargin (THA), an ERS inducer, attenuated the protective effect of PT against TNF-alpha-induced inflammation and ERS in HUVECs. Additionally, the downregulation of ERS signaling using siRNA targeting eIF2alpha and IRE1 not only inhibited ERS-related molecules but also simulated the therapeutic effects of PT on TNF-alpha-induced inflammation. In summary, PT treatment potently attenuates inflammation in vascular endothelial cells, which at least partly depends on the reduction of ERS. PMID- 26551860 TI - "God save us from psychologists as expert witnesses": the battle for forensic psychology in early twentieth-century Germany. AB - This article is focused on the jurisdictional battle between psychiatrists and psychologists over psychological expertise in legal contexts that took place during the first decades of the 20th century. Using, as an example, the debate between the psychologist William Stern, the psychiatrist Albert Moll, and the jurist Albert Hellwig, which occurred at the International Congress for Sexual Research held in Berlin in 1926, it aims to demonstrate the manner in which psychiatrists' responses to psychologists' attempts to gain admittance to Germany's courtrooms were shaped not only by epistemological and methodological objections, but also by changes to expert witnessing that had already encroached on psychiatrists' professional territory. Building upon recent work examining the relationship between psychologists and jurists prior to the First World War, this article also seeks to examine the role of judges and lawyers in the contest over forensic psychology in the mid-1920s, arguing that they ultimately became referees in the increasingly public disputes between psychiatrists and psychologists. PMID- 26551861 TI - The Hipp chronoscope versus the d'Arsonval chronometer: laboratory instruments measuring reaction times that distinguish German and French orientations of psychology. AB - Chronoscopes and chronographs were commonly used instruments that measured reaction times (RTs) in the first psychology laboratories. The Hipp chronoscope is commonly associated with the emergence of psychological laboratories in the late 19th century. This instrument is considered the key apparatus for the study of scientific psychology. Although German and American psychologists preferred the Hipp chronoscope, French psychologists of late 19th century favored another chronometer built by Jacques Arsene d'Arsonval (1851-1940). Unlike German and American psychologists, French psychologists demanded less precision in most experimental situations because they claimed that individual differences are very pronounced in a variety of situations. The advantage of the d'Arsonval chronometer was its portability and its simplicity. This article presents this chronometer and its advantages and drawbacks. The Hipp chronoscope and the d'Arsonval chronometer were the most commonly used apparatuses in Europe for the measurement of RTs until World War II, as is demonstrated by the catalogues of the time (Zimmermann and Boulitte). PMID- 26551862 TI - Theodor Waitz's theory of feelings and the rise of affective sciences in the mid 19th century. AB - The German psychologist Theodor Waitz (1821-1864) was an important theorist of affectivity in the mid-19th century. This article aims to revisit Waitz's contribution to affective psychology at a crucial moment of its history. First, I elaborate the context in which Waitz's ideas were carried out by showing how affective sciences emerged as an autonomous field of investigation between about 1770 and 1910. Second, I discuss the principles of Waitz's model of affectivity and their contextual significance. Third, I deal with the first major category of affective states identified by Waitz, namely, "formal feelings," which are supposed to be involved in the appraisal of the relational properties between representations. Fourth, I investigate "qualitative feelings," the second major category of affective states identified by Waitz, which refer to affective processes that relate to specific representational contents, namely, intellectual, aesthetic, and moral feelings. In conclusion, I emphasize the genealogical link between Waitz's pioneering research on musical feelings and current research on emotion and expectation in music. PMID- 26551864 TI - The influence of feeding crimped kernel maize silage on broiler production, nutrient digestibility and meat quality. AB - Two experiments were carried out in parallel with male Ross 308 broilers over 37 d. An experiment with a total of 736 broilers was performed to study the effect of dietary inclusion of crimped kernel maize silage (CKMS) on broiler production and meat quality. Another study with 32 broilers was carried out from 21 to 25 d to investigate the inclusion of CKMS on nutrient digestibility. In both trials, 4 dietary treatments were used: wheat-based feed (WBF), maize-based feed (MBF), maize-based feed supplemented with 15% CKMS (CKMS-15) and maize-based feed supplemented with 30% CKMS (CKMS-30). Compared with MBF, the dry matter (DM) intakes of broilers receiving CKMS-15 and CKMS-30, respectively, were numerically 7.5 and 6.2% higher and feed conversion ratio 6 and 12% poorer (significant for 30% CKMS), although there were no significant differences in AME content between the three diets. At 37 d, the body weight of birds receiving 15% CKMS was similar to birds fed with MBF. However, the inclusion of 30% CKMS decreased broiler growth. Dietary supplementation with CKMS significantly reduced the apparent digestibility of phosphorus. The fat digestibility was significantly lower for CKMS-30 than for the other three diets. Broiler mortality decreased significantly when CKMS was added to the diet. The consumption of drinking water was significantly lower in all maize-based diets as compared to WBF and was lowest in broilers fed with CKMS-30. An improved litter quality in terms of DM content and a lower frequency of foot pad lesions was observed with broilers supplemented with both dietary levels of CKMS. The addition of CKMS to maize-based diets increased juiciness, tenderness and crumbliness of the meat. In conclusion, the dietary supplementation of 15% CKMS had no negative effect on broiler growth and positively influenced bird welfare in terms of mortality and foot pad health. Therefore, the addition of 15% CKMS to maize-based diets is considered an advantageous feeding strategy in broiler production. PMID- 26551865 TI - Linear Interaction Energy Based Prediction of Cytochrome P450 1A2 Binding Affinities with Reliability Estimation. AB - Prediction of human Cytochrome P450 (CYP) binding affinities of small ligands, i.e., substrates and inhibitors, represents an important task for predicting drug drug interactions. A quantitative assessment of the ligand binding affinity towards different CYPs can provide an estimate of inhibitory activity or an indication of isoforms prone to interact with the substrate of inhibitors. However, the accuracy of global quantitative models for CYP substrate binding or inhibition based on traditional molecular descriptors can be limited, because of the lack of information on the structure and flexibility of the catalytic site of CYPs. Here we describe the application of a method that combines protein-ligand docking, Molecular Dynamics (MD) simulations and Linear Interaction Energy (LIE) theory, to allow for quantitative CYP affinity prediction. Using this combined approach, a LIE model for human CYP 1A2 was developed and evaluated, based on a structurally diverse dataset for which the estimated experimental uncertainty was 3.3 kJ mol-1. For the computed CYP 1A2 binding affinities, the model showed a root mean square error (RMSE) of 4.1 kJ mol-1 and a standard error in prediction (SDEP) in cross-validation of 4.3 kJ mol-1. A novel approach that includes information on both structural ligand description and protein-ligand interaction was developed for estimating the reliability of predictions, and was able to identify compounds from an external test set with a SDEP for the predicted affinities of 4.6 kJ mol-1 (corresponding to 0.8 pKi units). PMID- 26551866 TI - Sanitation, Stress, and Life Stage: A Systematic Data Collection Study among Women in Odisha, India. AB - Emerging evidence demonstrates how inadequate access to water and sanitation is linked to psychosocial stress, especially among women, forcing them to navigate social and physical barriers during their daily sanitation routines. We examine sanitation-related psychosocial stress (SRPS) across women's reproductive lives in three distinct geographic sites (urban slums, rural villages, and rural tribal villages) in Odisha, India. We explored daily sanitation practices of adolescent, newly married, pregnant, and established adult women (n = 60) and identified stressors encountered during sanitation. Responding to structured data collection methods, women ranked seven sanitation activities (defecation, urination, menstruation, bathing, post-defecation cleaning, carrying water, and changing clothes) based on stress (high to low) and level of freedom (associated with greatest freedom to having the most restrictions). Women then identified common stressors they encountered when practicing sanitation and sorted stressors in constrained piles based on frequency and severity of each issue. The constellation of factors influencing SRPS varies by life stage and location. Overall, sanitation behaviors that were most restricted (i.e., menstruation) were the most stressful. Women in different sites encountered different stressors, and the level of perceived severity varied based on site and life stage. Understanding the influence of place and life stage on SRPS provides a nuanced understanding of sanitation, and may help identify areas for intervention. PMID- 26551867 TI - Mucoadhesive thermo-responsive chitosan-g-poly(N-isopropylacrylamide) polymeric micelles via a one-pot gamma-radiation-assisted pathway. AB - Thermo-sensitive graft copolymer amphiphiles of chitosan (CS) and poly(N isopropylacrylamide) (PNiPAAm), CS-g-PNIPAAm, were successfully synthesized by a catalyst-less one-pot gamma (gamma)-radiation-assisted free radical polymerization at three different radiation doses: 5, 10 and 20 kGy. The chemical structure of the copolymers was confirmed by FTIR and solid-state (13)C NMR and the grafting extent by (1)H NMR and gravimetric analysis. In general, the higher the dose, the smaller the grafting due to the more significant NiPAAm homopolymerization. Due to the grafting of poly(NiPAAm) blocks, aqueous solutions of the different copolymers underwent a sharp transition upon heating above 32 degrees C, the characteristic lower critical solution temperature (LCST) of poly(NiPAAm). Then, the critical micellar concentration (CMC), the size and size distribution and the zeta-potential were characterized by dynamic light scattering (DLS) and the polymeric micelles visualized in suspension and quantified by Nanoparticle Tracking Analysis (NTA), at 37 degrees C. CMC values were in the 0.0012-0.0025%w/v range and micelles displayed sizes between 99 and 203 nm with low polydispersity (<0.160) and highly positive zeta-potential (>+15 mV) that suggested the partial conservation of the amine groups upon NiPAAm grafting. Consequently, polymeric micelles displayed the intrinsic mucoadhesiveness of CS, as established in vitro by the mucin solution assay. Finally, the encapsulation capacity of the micelles was assessed with the highly hydrophobic protease inhibitor antiretroviral indinavir free base (IDV). Polymeric micelles led to a significant 24-fold increase of the aqueous solubility from 63 MUg/mL to 1.45 mg/mL, a performance remarkably better than different poly(ethylene oxide)-b-poly(propylene oxide) block copolymers assessed before. Overall results highlight the potential of this nanotechnology platform to expand the application of polymeric micelles to mucosal administration routes. PMID- 26551868 TI - Propolis as lipid bioactive nano-carrier for topical nasal drug delivery. AB - Propolis shows therapeutic properties ascribed to the presence of some flavonoids, phenolic acids, and their esters; it is a natural multifunctional material, solid at room temperature, and composed mainly of resin and waxes. We therefore used propolis as a lipid material to prepare solid lipid nanoparticles (SLNs); SLNs are proposed bioactive medications for topical intranasal therapy. Suitable formulation parameters were studied and the SLNs obtained by the high shear homogenization method were characterized; a selected formulation was viscosized to increase the residence time. Dimensional, morphological, and solid state characterizations of the formulated SLNs were performed. In vitro and ex vivo permeation tests of diclofenac sodium, the model drug, and polyphenols were carried out. The propolis amount and surfactant concentration represent the key parameters that affect nanoparticle properties in terms of size, drug and polyphenol content, and physical stability. Size dispersions of about 600 nm and 0.4 PI were obtained, which do not change by increasing the viscosity. Drug is encapsulated in SLNs, as demonstrated by FTIR and DSC analyses. In vitro and ex vivo studies prove that drug and polyphenols do not cross the membranes; therefore, propolis-based SLNs could be used as delivery systems of diclofenac and flavonoids for the local treatment of nasal cavity diseases. Due to propolis composition, the proposed formulation could be used as a bioactive medication in which the carrier can exert a complementary effect with the loaded drug. PMID- 26551869 TI - Spiral assembly of amphiphilic cytarabine prodrug assisted by probe sonication: Enhanced therapy index for leukemia. AB - In order to overcome the drawbacks of cytarabine (Ara-C), such as low lipophilicity as well as short plasma half-life and rapid inactivation, a new derivative of Ara-C was designed by incorporation into the non-toxic material, oleic acid (OA), obtaining an amphiphilic small molecular weight prodrug (OA Ara). By a simple amidation reaction, OA-Ara was synthesized successfully with a yield up to 61.32%. It was for the first time to see that the novel prodrug molecules could assemble into the unexpectedly spiral assembly under probe ultrasonication in aqueous solution. The oil/water partition coefficient (Ko/w) and the permeability of cell membrane of the prodrug were significantly increased compared with Ara-C molecules. In addition, OA-Ara molecules were stable in various pH solutions and artificial digestives, which indicated that it could be administrated orally. Cell viability assay showed that the prodrug displayed much higher antiproliferative effect against K562 and HL60 cells due to its improvement of the lipophilicity and penetrability of cell membrane. These findings demonstrate the feasibility of utilizing structural modification to broaden the clinic application of Ara-C and thus provide an effective new therapeutic alternative for leukemia. PMID- 26551870 TI - QCM-D for non-destructive real-time assessment of Pseudomonas aeruginosa biofilm attachment to the substratum during biofilm growth. AB - Quartz crystal microbalance with dissipation monitoring (QCM-D) was used to investigate initial adhesion and subsequent biofilm growth of wild-type Pseudomonas aeruginosa PAO1 and a pili-deficient (DeltapilA) mutant PAO1 strain. Clean, sterilized, silica-coated QCM-D crystals were pre-coated with lysogeny broth (LB), seeded with a PAO1 strain and allowed to grow for 20 h at 37 degrees C in fresh LB injected at 100 MUL/min. QCM-D signals obtained for the wild-type PAO1 strain during the seeding period depict a large positive frequency shift that returns to baseline after ~20 min that is absent in the DeltapilA mutants, suggesting a dynamic pili-mediated attachment event for the wild-type PAO1 strain. During the subsequent growth period, significant and characteristic differences in the acquired QCM-D signals were observed between the wild-type and the DeltapilA mutant. Confocal laser scanning microscopy (CLSM) of the biofilm on the crystal surface showed that these differences could not be explained by differences in the extent of biofilm growth alone. When interpreted according to a coupled resonance model, the QCM-D observations suggest that pili are essential for coupling the developing biomass to the sensor surface. Total internal reflection fluorescence microscopy (TIRF) supports the hypothesis that the characteristic QCM-D signal is indicative of a dynamic attachment event, mediated by pili cell surface appendages pulling the wild-type PAO1 closer to the surface during the seeding period. We show that QCM-D offers direct, non-disruptive, in situ measurements of biofilm-substrate attachment. This technique has the potential to improve the current understanding of biofilm formation phenomena. PMID- 26551871 TI - Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: Ocular anti-inflammatory applications. AB - This work aimed the design and development of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for the ocular delivery of Carprofen (CP) by a central rotatable composite design 2(3)+ star. NPs showed adequate size for ocular administration (189.50 +/- 1.67 nm), low polydispersity (0.01 +/- 0.01), negative charge surface (-22.80 +/- 0.66 mV) and optimal entrapment efficiency (74.70 +/- 0.95%). Physicochemical analysis confirmed that CP was dispersed inside the NPs. The drug release followed a first order kinetic model providing greater sustained CP release after lyophilization. Ex vivo permeation analysis through isolated rabbit cornea revealed that a sufficient amount of CP was retained in the tissue avoiding excessive permeation and thus, potential systemic levels. Ex vivo ocular tolerance results showed no signs of ocular irritancy, which was also confirmed by in vivo Draize test. In vivo ocular anti-inflammatory efficacy test confirmed an optimal efficacy of NPs and its potential application in eye surgery. PMID- 26551872 TI - Immobilization of bioactive plasmin reduces the thrombogenicity of metal surfaces. AB - Components of many vascular prostheses including endovascular stents, heart valves and ventricular assist devices are made using metal alloys. In these blood contacting applications, metallic devices promote blood clotting, which is managed clinically by profound platelet suppression and/or anticoagulation. Here it is proposed that the localized immobilization of bioactive plasmin, a critical mediator of blood clot stability, may attenuate metallic prosthesis-induced thrombus formation. Previously described approaches to covalently immobilize biomolecules on implantable materials have relied on complex chemical linker chemistry, increasing the possibility of toxic side effects and reducing bioactivity. We utilize a plasma deposited thin film platform to covalently immobilize biologically active plasmin on stainless steel substrates, including stents. A range of in vitro whole blood assays demonstrate striking reductions in thrombus formation. This approach has profound potential to improve the efficacy of a wide range of metallic vascular implants. PMID- 26551873 TI - The protective and anti-inflammatory effects of glucagon-like peptide-2 in an experimental rat model of necrotizing enterocolitis. AB - Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease, that affects premature infants. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic hormone and reduces the inflammation. We suspected that GLP-2 would have protective and anti-inflammatory effects in an experimental rat model of NEC. NEC was induced in newborn rats by enteral feeding with hyperosmolar formula, asphyxial stress and enteral administration of lipopolysaccharide (LPS). Rats were randomly divided into the following four groups: dam-fed, NEC, NEC+GLP-2(L) given 80 MUg/kg/day of GLP-2, and NEC+GLP-2(H) given 800 MUg/kg/day of GLP-2. GLP 2 was administered subcutaneously every 6 h before stress. All animals surviving beyond 96 h or any that developed signs of distress were euthanized. The clinical sickness score in the NEC+GLP-2(H) group was significantly lower than that in the NEC group. The NEC score and the survival rate in the NEC+GLP-2(H) group was significantly improved compared with those in the NEC and the NEC+GLP-2(L) groups. Villous height and crypt depth in both the GLP-2 treatment groups were significantly increased compared with those in the NEC group. There were no significant differences in the crypt cell proliferation indices among the groups. Ileal interstitial TNF-alpha and IL-6 level in the NEC+GLP-2(H) group was decreased to the same levels in the dam-fed group. High dose GLP-2 administration improved the incidence and survival rate for NEC. It also decreased mucosal inflammatory cytokine production. These results support a potential therapeutic role for GLP-2 in the treatment of NEC. PMID- 26551874 TI - Endogenous opiates and behavior: 2014. AB - This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress induced analgesia); alcohol and drugs of abuse (emotional responses in opioid mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). PMID- 26551875 TI - Antidotes for poisoning by alcohols that form toxic metabolites. AB - The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience. PMID- 26551876 TI - Robust Superhydrophobic Foam: A Graphdiyne-Based Hierarchical Architecture for Oil/Water Separation. AB - Robust superhydrophobic foam is fabricated by combining an ordered graphdiyne based hierarchical structure with a low-surface-energy coating. This foam shows not only superhydrophobicity both in air (~160.1 degrees ) and in oil (~171.0 degrees ), but also high resistance toward abrasion cycles. Owing to its 3D porous structures and numerous superhydrophobic surfaces, it can easily separate oil from water with high efficiency and good recyclability. PMID- 26551878 TI - Assessment of nitric oxide (NO) redox reactions contribution to nitrous oxide (N2 O) formation during nitrification using a multispecies metabolic network model. AB - Over the coming decades nitrous oxide (N2O) is expected to become a dominant greenhouse gas and atmospheric ozone depleting substance. In wastewater treatment systems, N2O is majorly produced by nitrifying microbes through biochemical reduction of nitrite (NO2(-)) and nitric oxide (NO). However it is unknown if the amount of N2O formed is affected by alternative NO redox reactions catalyzed by oxidative nitrite oxidoreductase (NirK), cytochromes (i.e., P460 [CytP460] and 554 [Cyt554 ]) and flavohemoglobins (Hmp) in ammonia- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In this study, a mathematical model is developed to assess how N2O formation is affected by such alternative nitrogen redox transformations. The developed multispecies metabolic network model captures the nitrogen respiratory pathways inferred from genomes of eight AOB and NOB species. The performance of model variants, obtained as different combinations of active NO redox reactions, was assessed against nine experimental datasets for nitrifying cultures producing N2O at different concentration of electron donor and acceptor. Model predicted metabolic fluxes show that only variants that included NO oxidation to NO2(-) by CytP460 and Hmp in AOB gave statistically similar estimates to observed production rates of N2O, NO, NO2(-) and nitrate (NO3(-)), together with fractions of AOB and NOB species in biomass. Simulations showed that NO oxidation to NO2(-) decreased N2O formation by 60% without changing culture's NO2(-) production rate. Model variants including NO reduction to N2O by Cyt554 and cNor in NOB did not improve the accuracy of experimental datasets estimates, suggesting null N2O production by NOB during nitrification. Finally, the analysis shows that in nitrifying cultures transitioning from dissolved oxygen levels above 3.8 +/- 0.38 to <1.5 +/- 0.8 mg/L, NOB cells can oxidize the NO produced by AOB through reactions catalyzed by oxidative NirK. PMID- 26551877 TI - A Leadless Intracardiac Transcatheter Pacing System. AB - BACKGROUND: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. METHODS: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (<=2.0 V at a pulse width of 0.24 msec and an increase of <=1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies. RESULTS: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001). CONCLUSIONS: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.). PMID- 26551879 TI - Ethnopharmacological uses of Sempervivum tectorum L. in southern Serbia: Scientific confirmation for the use against otitis linked bacteria. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sempervivum tectorum L. (Crassulaceae), known as houseleek, is used in traditional medicine in the treatment of ear inflammation. It can be spread as a pack on wounds, sores, burns, and abscesses and also on painful areas attacked by gout as a refrigerant and astringent. Drinking tea prepared from leaves of S. tectorum is recommended for ulcer treatment. The present study was designed to investigate ethopharmacological use of S. tectorum in the southern Serbia and to further scientifically justify and confirm effectiveness of the leaf juice used in ethnomedicine for ear inflammation, against otitis linked bacteria. MATERIAL AND METHODS: Ethnopharmacological survey on the use of S. tectorum in southern Serbia was performed using semi structured questionnaires via a face-to-face interview. Chemical composition of the leaf juice regarding phenolic compounds and organic acids was analyzed. Antimicrobial activity was tested on bacteria isolated from ear swabs of the patients suffering from the ear pain (otitis). Anti-quorum-sensing activities of the juice were further investigated on Pseudomonas aeruginosa. RESULTS: Ethnopharmacological survey revealed the use of S. tectorum in southern Serbia for the treatment of ear pain, warts, cancer, stomachache, ulcer and high blood sugar level with the highest fidelity level (FL) for the ear pain. The phenolic composition of the S. tectorum leaf juice consisted of flavonol glycosides, with kaempferol-3-O rhamnosyl-glucoside-7-O-rhamnoside as the majority compound. Organic acids composition revealed malic acid as the most dominant one. Antimicrobial and anti quorum-sensing activities of the juice showed to be promising. CONCLUSION: Ethnopharmacological use of S. tectorum juice for treating ear pain is justified, since the juice possessed antimicrobial activity towards clinical isolates of bacteria linked to otitis. PMID- 26551881 TI - Prevalence of Human Cytomegalovirus and Epstein-Barr Virus in Chronic Periapical Lesions. AB - OBJECTIVE: The aim of this study was to investigate the presence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the tissue of chronic periapical lesions, and to compare the results in relation to the symptoms of patients and the size of the lesion. METHODS: Periapical lesions analyzed in the study were collected from the roots of the teeth indicated for extraction. Samples were divided according to the symptoms into groups of symptomatic and asymptomatic, and according the size into groups of small and large lesions. Polymerase chain reaction was used to detect HCMV and EBV. The amplification was performed in a DNA Thermal Cycler (Hybaid). RESULTS: Symptomatic lesions were 7.68 times more likely to be infected with HCMV than asymptomatic lesions (p < 0.001). Large symptomatic lesions were 73.50 times more likely to harbor HCMV than small symptomatic lesions (p < 0.001). Large symptomatic lesions were 7.64 times more likely to be infected with EBV than small symptomatic lesions (p = 0.05). Large symptomatic lesions were 5.38 times more likely to harbor dual HCMV/EBV infection than small symptomatic lesions (p = 0.115). CONCLUSION: Detection of HCMV and EBV in the samples of periapical lesions suggests an important role of herpesviruses in periapical tissue destruction. PMID- 26551880 TI - The cytotoxic T cell proteome and its shaping by the kinase mTOR. AB - We used high-resolution mass spectrometry to map the cytotoxic T lymphocyte (CTL) proteome and the effect of the metabolic checkpoint kinase mTORC1 on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes, and mTORC1 selectively repressed and promoted expression of a subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for negative control of the production of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) by mTORC1 in CTLs. mTORC1 repressed PtdIns(3,4,5)P3 production and determined the requirement for mTORC2 in activation of the kinase Akt. Our unbiased proteomic analysis thus provides comprehensive understanding of CTL identity and the control of CTL function by mTORC1. PMID- 26551882 TI - Cardiac MRI-based multi-modality imaging in clinical decision-making: Preliminary assessment of a management algorithm for patients with suspected cardiac mass. AB - BACKGROUND: Cardiac masses are rare with high morbidity and mortality that challenging the management. The purpose of this study was to evaluate the potential role of cardiac-MRI based multi-modality imaging in the clinical decision-making for patients with cardiac mass. METHODS: From November 2011 to May 2014, 59 consecutive patients (33 females; mean age, 48.2 +/- 21.1 [range, 0.6-85] years) with suspected cardiac mass were enrolled in this prospective single center study, underwent MRI based multi-modality imaging and were followed up for survival status. Management strategy (surgery, chemotherapy or observation) was based on patient's clinical status and cardiac mass imaging characteristics (location, morphology, hemodynamics, embolization risk, metastasis, and resectability). RESULTS: Using cardiac MRI, 39 patients were diagnosed with intra-cardiac neoplasm (28 benign, 11 malignant) and 20 with pseudo-tumors (13 thrombi, 4 cysts and 3 fat infiltration); 34 masses (23 neoplasms, 11 pseudo-tumors) were eligible for surgical removal, and 4 underwent PET-CT scan to further delineate characteristics and metastasis. Pathological examination revealed high accuracy of cardiac MRI in differentiating benign from malignant tumors (96%), and neoplasm from pseudo-tumors (100%). As for the 16 patients with cardiac neoplasm not surgically treated, the 9 with "benign" masses as per MRI-based multimodality imaging survived during follow-up, while all 7 with "malignancy" died; the 9 with pseudo-tumors not surgically treated also survived with good condition. The median follow-up period is 2 years (10 days-3 years). CONCLUSION: Cardiac MRI based multimodality imaging appears useful for risk stratification and clinical decision making for patients with suspected cardiac mass. PMID- 26551883 TI - Therapeutic effects of late outgrowth endothelial progenitor cells or mesenchymal stem cells derived from human umbilical cord blood on infarct repair. AB - BACKGROUND: This study sought to systematically investigate the derivation of late outgrowth endothelial progenitor cells (late EPC) and mesenchymal stem cells (MSC) from umbilical cord blood (UCB) and to examine their therapeutic effects on myocardial infarction (MI). METHODS: The expression of angiogenic genes was determined by qRT-PCR. Myocardial infarction (MI) was induced in rats, and cells were directly transplanted into the border regions of ischemic heart tissue. RESULTS: Culture of UCB mononuclear cells yielded two distinct types of cells by morphology after 2 weeks in the same culture conditions. These cells were identified as late EPC and MSC, and each was intramyocardially injected into rat hearts after induction of MI. Echocardiography and histologic analyses demonstrated that both EPC and MSC improved cardiac function and enhanced vascularization, although fibrosis was reduced only in the EPC transplanted hearts. Different paracrine factors were enriched in EPC and MSC. However, once injected into the hearts, they induced similar types of paracrine factors in the heart. Transplanted EPC or MSC were mostly localized at the perivascular areas. This study demonstrated that EPC and MSC can be simultaneously derived from UCB under the same initial culture conditions, and that common paracrine factors are involved in the repair of MI. CONCLUSION: Late EPC and MSC are effective for infarct repair, apparently mediated through common humoral mechanisms. PMID- 26551884 TI - Sudden cardiac death in neuromuscular disorders. AB - OBJECTIVES: The heart is frequently affected in neuromuscular disorders (NMDs). Some of these patients even experience sudden cardiac death (SCD). In the following review, we summarize recent findings concerning epidemiology, risk stratification, and prevention of SCD in NMDs. METHODS: Review of publications about SCD and NMDs by search of MEDLINE applying appropriate search terms. RESULTS: NMDs in which SCD was most frequently reported include myotonic dystrophy type 1, mitochondrial disorders, laminopathy, desminopathy, Danon disease, and amyotrophic lateral sclerosis. Risk factors for developing SCD vary considerably between NMDs and include positive family history for SCD, palpitations, arterial hypertension, ECG-abnormalities (bundle branch block, bifascicular block, QT-prolongation, increased QT-variability, early repolarization, T-wave alternans, ventricular tachycardia), late gadolinium enhancement as an equivalent of myocardial fibrosis, and noncompaction. NMD patients at risk for SCD require a thorough history, long-term ECG recordings, and cardiac MRI with contrast medium. In case a propensity for ventricular arrhythmias is documented, implantation of an implantable cardioverter defibrillator should be considered. CONCLUSIONS: SCD is the cause of death in various NMDs why these patients need to be thoroughly screened for risk factors of SCD. Verification of risk factors for SCD in NMDs requires appropriate management. PMID- 26551885 TI - Rare copy number variations in an adult with transposition of the great arteries emphasize the importance of updated genetic assessments in syndromic congenital cardiac disease. PMID- 26551886 TI - Response to the letter regarding article "Atrial fibrillation is a risk marker for worse in-hospital and long-term outcome in patients with peripheral artery disease". PMID- 26551888 TI - Microbiological characterization using combined culture dependent and independent approaches of Casizolu pasta filata cheese. AB - AIMS: Casizolu is a traditional Sardinian (Italy) pasta filata cheese made with cow raw milk belonging to Sardo-Modicana and/or Bruno-Sarda breeds added with natural whey starter. This work aims to describe the traditional technology of this product and to evaluate the microbial groups/species involved in the first month of ripening. METHODS AND RESULTS: Raw milk, curd after stretching and Casizolu cheese samples from two different farmsteads were subjected to enumeration of microbial groups, isolation and genotypic characterization of isolates and PCR temporal temperature gel electrophoresis (TTGE) analysis. The counts of lactobacilli and lactococci groups in raw milk were about 5-6 log UFC ml(-1) of milk. These counts tended to increase in curd and cheeses, reaching values higher than 8 log UFC g(-1) of cheese. Culture dependent and independent approaches employed in this work highlighted the fundamental role of Lactococcus lactis subsp. lactis, Streptococcus thermophilus and Lactobacillus paracasei in the manufacture and ripening of Casizolu cheese. Other species frequently isolated were Enterococcus durans, Enterococcus faecium, Enterococcus italicus while Enterococcus lactis, Streptococcus parauberis, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus brevis, Lactobacillus fermentum and Lactococcus raffinolactis were isolated occasionally. CONCLUSIONS: Lactococcus lactis subsp. lactis, Strep. thermophilus and Lact. paracasei were the principal bacterial species involved in the Casizolu cheese manufacturing and ripening. For the first time, Ent. italicus and Ent. lactis were isolated in the pasta filata cheese. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the first data on microbial groups and species involved in the manufacture of Casizolu cheese and highlights the role of Lact. paracasei and Enterococcus spp. from the earliest stages of ripening cheese; furthermore, provides evidence that raw milk cheese is a source of new strains and therefore a reservoir of microbial biodiversity. PMID- 26551887 TI - The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with high mortality. Treatments, which can result in significant morbidity, have not substantially changed in three decades. The second messenger cyclic GMP (cGMP), which targets protein kinase G (PKG), is generated by guanylate cyclases (GCs), and is rapidly hydrolyzed by phosphodiesterases (PDEs). Activation of the cGMP/PKG pathway is antineoplastic in several cancer types, but its impact on HNSCC has not been fully exploited. We found differential expression of critical components of this pathway in four HNSCC cell lines. Several activators of soluble GC (sGC), as well as inhibitors of PDE5, increased intracellular cGMP, reduced cell viability, and induced apoptosis in HNSCC cells. The apoptotic effects of the sGC activator BAY 41-2272 and the PDE5 inhibitor Tadalafil (Cialis) were mediated by PKG. Furthermore, Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. PMID- 26551889 TI - Response to gonadotropin-releasing hormone challenge: Seasonal variation in steroid production in a viviparous lizard, Tiliqua nigrolutea. AB - The hypothalamic-pituitary-gonadal axis plays a central role in the regulation of gamete maturation, sex steroid production and the stimulation of reproductive behaviours in vertebrates. In seasonal breeders, the timely activation and deactivation of this control system is important to ensure successful reproduction: this process is not well understood in species which breed irregularly. Males of the viviparous blotched blue-tongued lizard, Tiliqua nigrolutea, breed annually, while females display a multiennial cycle. We investigated seasonal variation in hypothalamic-pituitary-gonadal axis responsiveness in both sexes of T. nigrolutea. We measured changes in plasma concentrations of testosterone and estrogen in response to a single intraperitoneal injection of a GnRH agonist, chicken-II LH-RH, at three reproductively distinct times of year. Plasma testosterone concentrations in males were significantly increased during gonadal quiescence, but not initial or final spermatogenesis. There was no estrogen response in males at any time of year. Conversely, in females, there was an increase in plasma testosterone, but not estrogen, concentration, in reproductively quiescent females several months in advance of a successful pregnancy. These results indicate clear variation in HPG axis activity with sex, season and reproductive condition in this seasonally breeding viviparous lizard. This study opens the way for further investigation into the mechanisms by which internal (body condition) and external seasonal cues (temperature and photoperiod) are coordinated to regulate reproduction in irregularly-breeding reptiles. PMID- 26551890 TI - Transformation and Immobilization of Chromium by Arbuscular Mycorrhizal Fungi as Revealed by SEM-EDS, TEM-EDS, and XAFS. AB - Arbuscular mycorrhizal fungi (AMF), ubiquitous soil fungi that form symbiotic relationships with the majority of terrestrial plants, are known to play an important role in plant tolerance to chromium (Cr) contamination. However, the underlying mechanisms, especially the direct influences of AMF on the translocation and transformation of Cr in the soil-plant continuum, are still unresolved. In a two-compartment root-organ cultivation system, the extraradical mycelium (ERM) of mycorrhizal roots was treated with 0.05 mmol L(-1) Cr(VI) for 12 days to investigate the uptake, translocation, and transformation of Cr(VI) by AMF using inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy equipped with energy-dispersive spectroscopy (SEM-EDS), transmission electron microscopy equipped with energy-dispersive spectroscopy (TEM-EDS), and X-ray-absorption fine structure (XAFS) technologies. The results indicated that AMF can immobilize quantities of Cr via reduction of Cr(VI) to Cr(III), forming Cr(III)-phosphate analogues, likely on the fungal surface. Besides this, we also confirmed that the extraradical mycelium (ERM) can actively take up Cr [either in the form of Cr(VI) or Cr(III)] and transport Cr [potentially in the form of Cr(III)-histidine analogues] to mycorrhizal roots but immobilize most of the Cr(III) in the fungal structures. Based on an X-ray absorption near-edge spectroscopy analysis of Cr(VI)-treated roots, we proposed that the intraradical fungal structures can also immobilize Cr within mycorrhizal roots. Our findings confirmed the immobilization of Cr by AMF, which plays an essential role in the Cr(VI) tolerance of AM symbioses. PMID- 26551891 TI - Current state of biomarkers in ovarian cancer prognosis. AB - High-grade serous ovarian cancer remains one of the most lethal malignancies in women. Despite recent advances in surgical and pharmaceutical therapies, survival rates remain poor. A major impediment in management of this disease, that continues to contribute to poor overall survival rates, is resistance to standard carboplatin-paclitaxel combination chemotherapies. In addition to tumor cell intrinsic mechanisms leading to drug resistance, there is increasing awareness of the crucial role of the tumor microenvironment in mediating natural immune defense mechanisms and selective pressures that appear to facilitate chemotherapy sensitivity. We provide an overview of some of the promising new genetic and immunological biomarkers in ovarian cancer and discuss their biology and their likely clinical utility in future ovarian cancer management. PMID- 26551893 TI - Hypnosis modulates behavioural measures and subjective ratings about external and internal awareness. AB - In altered subjective states, the behavioural quantification of external and internal awareness remains challenging due to the need for reports on the subjects' behalf. With the aim to characterize the behavioural counterpart of external and internal awareness in a modified subjective condition, we used hypnosis during which subjects remain fully responsive. Eleven right-handed subjects reached a satisfactory level of hypnotisability as evidenced by subjective reports on arousal, absorption and dissociation. Compared to normal wakefulness, in hypnosis (a) participants' self-ratings for internal awareness increased and self-ratings for external awareness decreased, (b) the two awareness components tended to anticorrelate less and the switches between external and internal awareness self-ratings were less frequent, and (c) participants' reaction times were higher and lapses in key presses were more frequent. The identified imbalance between the two components of awareness is considered as of functional relevance to subjective (meta)cognition, possibly mediated by allocated attentional properties brought about by hypnosis. Our results highlight the presence of a cognitive counterpart in resting state, indicate that the modified contents of awareness are measurable behaviourally, and provide leverage for investigations of more challenging altered conscious states, such as anaesthesia, sleep and disorders of consciousness. PMID- 26551892 TI - Lifetime exposure to traumatic and other stressful life events and hair cortisol in a multi-racial/ethnic sample of pregnant women. AB - We examined whether lifetime exposure to stressful and traumatic events alters hypothalamic-pituitary-adrenal (HPA) axis functioning, as indexed by hair cortisol, regardless of associated psychopathology, among pregnant women of different racial/ethnic backgrounds. 180 women provided hair samples for measurement of integrated cortisol levels throughout pregnancy and information regarding their lifetime exposure to stressful and traumatic life events. Results indicate that increased lifetime exposure to traumatic events was associated with significantly greater hair cortisol over the course of pregnancy. Similarly, greater lifetime exposure to stressful and traumatic events weighted by reported negative impact (over the previous 12 months) was associated with significantly greater hair cortisol during pregnancy. All analyses controlled for maternal age, education, body mass index (BMI), use of inhaled corticosteroids, race/ethnicity, and post-traumatic stress disorder (PTSD) and depressive symptoms. Following stratification by race/ethnicity, associations between stressful and traumatic life events and hair cortisol were found among Black women only. This is the first study to consider associations between lifetime stress exposures and hair cortisol in a sociodemographically diverse sample of pregnant women. Increased exposure to stressful and traumatic events, independent of PTSD and depressive symptoms, was associated with higher cortisol production, particularly in Black women. Future research should investigate the influence of such increased cortisol exposure on developmental outcomes among offspring. PMID- 26551894 TI - The vgll3 Locus Controls Age at Maturity in Wild and Domesticated Atlantic Salmon (Salmo salar L.) Males. AB - Wild and domesticated Atlantic salmon males display large variation for sea age at sexual maturation, which varies between 1-5 years. Previous studies have uncovered a genetic predisposition for variation of age at maturity with moderate heritability, thus suggesting a polygenic or complex nature of this trait. The aim of this study was to identify associated genetic loci, genes and ultimately specific sequence variants conferring sea age at maturity in salmon. We performed a genome wide association study (GWAS) using a pool sequencing approach (20 individuals per river and phenotype) of male salmon returning to rivers as sexually mature either after one sea winter (2009) or three sea winters (2011) in six rivers in Norway. The study revealed one major selective sweep, which covered 76 significant SNPs in which 74 were found in a 370 kb region of chromosome 25. Genotyping other smolt year classes of wild and domesticated salmon confirmed this finding. Genotyping domesticated fish narrowed the haplotype region to four SNPs covering 2386 bp, containing the vgll3 gene, including two missense mutations explaining 33-36% phenotypic variation. A single locus was found to have a highly significant role in governing sea age at maturation in this species. The SNPs identified may be both used as markers to guide breeding for late maturity in salmon aquaculture and in monitoring programs of wild salmon. Interestingly, a SNP in proximity of the VGLL3 gene in humans (Homo sapiens), has previously been linked to age at puberty suggesting a conserved mechanism for timing of puberty in vertebrates. PMID- 26551895 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. AB - This commentary considers a recent article on how the proliferating use of atheoretical, confirmatory and diagnosis driven research approaches is resulting in the over-identification of behavioral addictions. In response to the original article, I reflect on the timeliness and value of its observations and expand on a central point it raises: The importance of thinking beyond diagnostic frameworks in developing a comprehensive understanding of addictive behaviors and associated treatments. PMID- 26551896 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Problems with atheoretical and confirmatory research approaches in the study of behavioral addictions. AB - BACKGROUND AND AIMS: This commentary is written in response to a paper by Billieux, Schimmenti, Khazaal, Maurage and Hereen (2015) published in the Journal of Behavioral Addictions. METHODS: It supports and extends the arguments by Billieux, Schimmenti et al. (2015): that the study of behavioral addictions too often rests on atheoretical and confirmatory research approaches. This tends to lead to theories that lack specificity and a neglect of the underlying processes that might explain why repetitive problem behaviors occur. RESULTS: In this commentary I extend the arguments by Billieux, Schimmenti et al. (2015) and argue that such research approaches might take us further away from conceptualizing psychiatric diagnoses that can be properly validated, which is already a problem in the field. Furthermore, I discuss whether the empirical support for conceptualizing repetitive problem behaviors as addictions might rest on research practices that have been methodologically biased to produce a result congruent with the proposal that substance addictions and behavioral addictions share similar traits. CONCLUSIONS: I conclude by presenting a number of ways of going forward, chief of which is the proposal that we might wish to go beyond a priori assumptions of addiction in favor of identifying the essential problem manifestations for each new potential behavioral addiction. PMID- 26551897 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Excessive behaviors are not necessarily addictive behaviors. AB - BACKGROUND AND AIMS: The commentary aims to provide clarity to the article "Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research." METHODS: We provide another viewpoint for the important issues of behavior addiction. RESULT: The course of behavior addiction should be further studied. The criteria of withdrawal and tolerance of behavior addiction are ill defined and need to be further evaluated. CONCLUSIONS: The etiology, course, presentation, and functional impairment of behavior addiction should be validated by evidence-based data before being defined as a disorder. PMID- 26551898 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. On the slippery slopes: The case of gambling addiction. AB - Billieux et al. (2015) propose that the recent proliferation of behavioral addictions has been driven by deficiencies in the underlying research strategy. This commentary considers how pathological gambling (now termed gambling disorder) traversed these challenges to become the first recognized behavioral addiction in the DSM-5. Ironically, many similar issues continue to exist in research on gambling disorder, including question-marks over the validity of tolerance, heterogeneity in gambling motives, and the under-specification of neuroimaging biomarkers. Nevertheless, I contend that the case for gambling disorder as a behavioral addiction has been bolstered by the existence of clear and consistent functional impairment (primarily in the form of debt), coupled with the development of a public health approach that has given emphasis to product features (i.e. the structural characteristics of gambling forms) as much as individual dispositions (the 'addictive personality'). PMID- 26551899 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. On functional and compulsive aspects of reinforcement pathologies. AB - BACKGROUND: This paper is a commentary to a debate article entitled: "Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research", by Billieux et al. (2015). METHODS AND AIM: This brief response focused on the necessity to better characterize psychological and related neurocognitive determinants of persistent deleterious actions associated or not with substance utilization. RESULTS: A majority of addicted people could be driven by psychological functional reasons to keep using drugs, gambling or buying despite the growing number of related negative consequences. In addition, a non-negligible proportion of them would need assistance to restore profound disturbances in basic learning processes involved in compulsive actions. CONCLUSIONS: The distinction between psychological functionality and compulsive aspects of addictive behaviors should represent a big step towards more efficient treatments. PMID- 26551900 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Defining and classifying non-substance or behavioral addictions. AB - Multiple controversies exist currently in the field of behavioral addictions. The opinion article by Billieux, Schimmenti, Khazaal, Maurage and Heeren (2015) proposes an approach to considering which behaviors might be considered as foci for addictions. The article raises multiple important points that foster further dialog and highlight the need for additional research. Given that how specific behaviors are considered from diagnostic and classification perspectives holds significant public health implications, targeting and eliminating current knowledge gaps relating to behavioral addictions is an important undertaking. PMID- 26551901 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. AB - This commentary supports the argument that there is an increasing tendency to subsume a range of excessive daily behaviors under the rubric of non-substance related behavioral addictions. The concept of behavioral addictions gained momentum in the 1990s with the recent reclassification of pathological gambling as a non-substance behavioral addiction in DSM-5 accelerating this process. The propensity to label a host of normal behaviors carried out to excess as pathological based simply on phenomenological similarities to addictive disorders will ultimately undermine the credibility of behavioral addiction as a valid construct. From a scientific perspective, anecdotal observation followed by the subsequent modification of the wording of existing substance dependence diagnostic criteria, and then searching for biopsychosocial correlates to justify classifying an excessive behavior resulting in harm as an addiction falls far short of accepted taxonomic standards. The differentiation of normal from non substance addictive behaviors ought to be grounded in sound conceptual, theoretical and empirical methodologies. There are other more parsimonious explanations accounting for such behaviors. Consideration needs to be given to excluding the possibility that excessive behaviors are due to situational environmental/social factors, or symptomatic of an existing affective disorder such as depression or personality traits characteristic of cluster B personalities (namely, impulsivity) rather than the advocating for the establishment of new disorders. PMID- 26551902 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Addictions as a psychosocial and cultural construction. AB - This commentary proposes a complementary perspective to that developed by Billieux, Schimmenti, Khazaal, Maurage and Heeren (2015). The addiction-as disease approach tends to sideline explanatory factors of a psychosocial, cultural, political, or historical nature. I therefore suggest taking into account not only the personal characteristics (loss of self-control, impulsivity) related to the disease model, but also the social determinants of addictive behaviors (weak social ties, social exclusion, hyperindividualism, poverty, unemployment, etc.). Moreover, the disease model of addiction removes addictive behaviors from the cultural and historical contexts that shape them. I argue that the cultural and historical reasons for which certain factors (such as loss of self-control) became so important in the explanation of addictive behaviors should be more thoroughly considered. PMID- 26551903 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Can the emerging domain of behavioral addictions bring a new reflection for the field of addictions, by stressing the issue of the context of addiction development? AB - BACKGROUND: This paper is a commentary to the article entitled: "Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research", by Billieux, Schimmenti, Khazaal, Maurage and Heeren (2015). METHODS AND AIMS: In this manuscript, we commented on two aspects developed by the authors. Billieux et al. (2015) propose that the recent development of propositions of behavioral addiction is driven by an unwise application of an addiction model to excessive behaviors and rests on a confirmatory research strategy that does not question the psychological processes underlying the development of the conduct. They also show that applying a process driven strategy leads to a more appropriate description of the reality of the behavior and conduct, in particular by describing a variety of motivations for the excessive behavior, which is central to understanding the nature of the conduct. We believe that this new approach, which is fruitful to the emerging domain of behavioral addictions, could also apply to the domain of addictions in general. The latter is characterized by the application of a generic biological model, largely influenced by animal models, focusing on neurophysiological determinants of addiction. This approach may have decreased the attention paid to dimensions of addictions that are more specifically human. We will firstly briefly argue on the limitation of this neurophysiological addiction model for the field of excessive behavioral conducts. Secondly, we will argue for an approach centered on the differentiation of motivations and on the adaptive dimension of the behavior when it first developed and on the evocation of a transition where the conduct became independent of its original function. CONCLUSIONS: The emerging domain of behavioral addictions, where no animal model has been developed so far, may bring a new reflection that may apply to the domain of addictions in general, with a specific attention to human questions. PMID- 26551904 TI - Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. The diagnostic pitfalls of surveys: If you score positive on a test of addiction, you still have a good chance not to be addicted. AB - BACKGROUND AND AIMS: Survey-based studies often fail to take into account the predictive value of a test, in other words, the probability of a person having (or not having) the disease when scoring positive (or negative) on the given screening test. METHODS: We re-visited the theory and basic calculations of diagnostic accuracy. RESULTS: In general, the lower the prevalence the worse the predictive value is. When the disorder is relatively rare, a positive test finding is typically not useful in confirming its presence given the high proportion of false positive cases. For example, using the Compulsive Buying Scale (Faber & O'Guinn, 1992) three in four people classified as having compulsive buying disorder will in fact not have the disorder. CONCLUSIONS: Screening tests are limited to serve as an early detection "gate" and only clinical (interview-based) studies are suitable to claim that a certain behaviour is truly "pathological". PMID- 26551905 TI - Addictive use of social networking sites can be explained by the interaction of Internet use expectancies, Internet literacy, and psychopathological symptoms. AB - BACKGROUND AND AIMS: Most people use the Internet in a functional way to achieve certain goals and needs. However, there is an increasing number of people who experience negative consequences like loss of control and distress based on an excessive use of the Internet and its specific online applications. Some approaches postulate similarities with behavioral addictions as well as substance dependencies. They differentiate between a generalized and a specific Internet addiction, such as the pathological use of social networking sites (SIA-SNS). Prior studies particularly identified the use of applications, personal characteristics, and psychopathological symptoms as significant predictors for the development and maintenance of this phenomenon. So far, it remains unclear how psychopathological symptoms like depression and social anxiety interact with individual expectancies of Internet use and capabilities of handling the Internet, summarized as Internet literacy. METHODS: The current study (N = 334) investigated the interaction of these components in a structural equation model. RESULTS: The results indicate that the effects of depression and social anxiety on SIA-SNS were mediated by Internet use expectancies and self-regulation. DISCUSSION: Thus, Internet use expectancies seem to be crucial for SIA-SNS, which is in line with prior models. CONCLUSIONS: SNS use may be reinforced by experienced gratification and relief from negative feelings. Individual competences in handling the Internet may be preventive for the development of SIA SNS. PMID- 26551906 TI - The independent relationship between trouble controlling Facebook use, time spent on the site and distress. AB - BACKGROUND AND AIMS: There is an emerging literature base on the relationship between maladaptive traits and "addiction" to social networking sites. These studies have operationalized addiction as either spending excessive amounts of time on social networking sites (SNS) or trouble controlling SNS use, but have not assessed the unique contribution of each of these constructs on outcomes in the same models. Moreover, these studies have exclusively been conducted with younger people rather than a heterogeneous sample. This study examined the independent relationship of a brief Facebook addiction scale, time spent on Facebook, and Facebook checking on positive and negative social domains, while controlling for self-esteem and social desirability. METHODS: Participants were recruited using e-mail, SNS posts and through Amazon's MTurk system. The sample included 489 respondents ages from 18 to approximately 70, who completed a 10-15 minute survey. RESULTS: Results indicate that neither time spent on Facebook nor Facebook checking was significantly associated with either self-esteem, fear of negative social evaluation or social comparison, while SNS addiction symptoms were each independently associated with Facebook usage. Neither time spent on Facebook nor SNS addiction symptoms were associated with positive social relationships. DISCUSSION: Overall results suggest that time on SNS and trouble controlling use should be considered independent constructs and that interventions should target underlying loss of control as the primary intervention target above ego syntonic time spent on the site. PMID- 26551907 TI - Do gamblers eat more salt? Testing a latent trait model of covariance in consumption. AB - A diverse class of stimuli, including certain foods, substances, media, and economic behaviours, may be described as 'reward-oriented' in that they provide immediate reinforcement with little initial investment. Neurophysiological and personality concepts, including dopaminergic dysfunction, reward sensitivity and rash impulsivity, each predict the existence of a latent behavioural trait that leads to increased consumption of all stimuli in this class. Whilst bivariate relationships (co-morbidities) are often reported in the literature, to our knowledge, a multivariate investigation of this possible trait has not been done. We surveyed 1,194 participants (550 male) on their typical weekly consumption of 11 types of reward-oriented stimuli, including fast food, salt, caffeine, television, gambling products, and illicit drugs. Confirmatory factor analysis was used to compare models in a 3*3 structure, based on the definition of a single latent factor (none, fixed loadings, or estimated loadings), and assumed residual covariance structure (none, a-priori / literature based, or post-hoc / data-driven). The inclusion of a single latent behavioural 'consumption' factor significantly improved model fit in all cases. Also confirming theoretical predictions, estimated factor loadings on reward-oriented indicators were uniformly positive, regardless of assumptions regarding residual covariances. Additionally, the latent trait was found to be negatively correlated with the non reward-oriented indicators of fruit and vegetable consumption. The findings support the notion of a single behavioural trait leading to increased consumption of reward-oriented stimuli across multiple modalities. We discuss implications regarding the concentration of negative lifestyle-related health behaviours. PMID- 26551908 TI - The role of negative mood states and consequences of hypersexual behaviours in predicting hypersexuality among university students. AB - BACKGROUND AND AIMS: The issue of whether hypersexual behaviours exist among university students is controversial because many of these individuals engage in sexual exploration during their time at university. To date, little is known about the correlates of hypersexual behaviours among university students in the UK. Therefore, the aims of this exploratory study were two-fold. Firstly, to explore and establish the correlates of hypersexual behaviours, and secondly, to investigate whether hypersexuality among university students can be predicted by variables relating to negative mood states (i.e., emotional dysregulation, loneliness, shame, and life satisfaction) and consequences of hypersexual behaviour. METHODS: Survey data from 165 British university students was analysed using regression analyses. RESULTS: The full regression model significantly predicted hypersexual behaviours. However, only a small number of predictor variables (i.e., gender, consequences of hypersexual behaviours, life satisfaction and emotional dysregulation) accounted for the significant unique influence on hypersexual behaviours among the sample. CONCLUSIONS: The study empirically supported the concept of hypersexual disorder. The implications of these findings are also discussed. PMID- 26551909 TI - Prevalence and co-occurrence of addictive behaviors among former alternative high school youth: A longitudinal follow-up study. AB - BACKGROUND AND AIMS: Recent work has studied addictions using a matrix measure, which taps multiple addictions through single responses for each type. This is the first longitudinal study using a matrix measure. METHODS: We investigated the use of this approach among former alternative high school youth (average age = 19.8 years at baseline; longitudinal n = 538) at risk for addictions. Lifetime and last 30-day prevalence of one or more of 11 addictions reviewed in other work was the primary focus (i.e., cigarettes, alcohol, hard drugs, shopping, gambling, Internet, love, sex, eating, work, and exercise). These were examined at two time points one year apart. Latent class and latent transition analyses (LCA and LTA) were conducted in Mplus. RESULTS: Prevalence rates were stable across the two time-points. As in the cross-sectional baseline analysis, the 2-class model (addiction class, non-addiction class) fit the data better at follow-up than models with more classes. Item-response or conditional probabilities for each addiction type did not differ between time-points. As a result, the LTA model utilized constrained the conditional probabilities to be equal across the two time-points. In the addiction class, larger conditional probabilities (i.e., 0.40 0.49) were found for love, sex, exercise, and work addictions; medium conditional probabilities (i.e., 0.17-0.27) were found for cigarette, alcohol, other drugs, eating, Internet and shopping addiction; and a small conditional probability (0.06) was found for gambling. DISCUSSION AND CONCLUSIONS: Persons in an addiction class tend to remain in this addiction class over a one-year period. PMID- 26551910 TI - The influence of exercise identity and social physique anxiety on exercise dependence. AB - BACKGROUND: Previous research has identified exercise identity and social physique anxiety as two independent factors that are associated with exercise dependence. AIMS: The purpose of our study was to investigate the unique and interactive effect of these two known correlates of exercise dependence in a sample of 1,766 female runners. METHODS: Regression analyses tested the main effects of exercise identity and social physique anxiety on exercise dependence. An interaction term was calculated to examine the potential moderating effect of social physique anxiety on the exercise identity and exercise dependence relationship. RESULTS: Results indicate a main effect for exercise identity and social physique anxiety on exercise dependence; and the interaction of these factors explained exercise dependence scores beyond the independent effects. Thus, social physique anxiety acted as a moderator in the exercise identity and exercise dependence relationship. DISCUSSION: Our results indicate that individuals who strongly identify themselves as an exerciser and also endorse a high degree of social physique anxiety may be at risk for developing exercise dependence. CONCLUSIONS: Our study supports previous research which has examined factors that may contribute to the development of exercise dependence and also suggests a previously unknown moderating relationship for social physique anxiety on exercise dependence. PMID- 26551911 TI - Relationship between smartphone addiction and physical activity in Chinese international students in Korea. AB - BACKGROUND AND AIMS: Excessive usage of smartphones may induce social problems, such as depression and impairment of social and emotional functioning. Moreover, its usage can impede physical activity, but the relationship between smartphone addiction and physical activity is obscure. Therefore, we examined the relationship and the impact of excessive smartphone use on physical activity. METHODS: This study collected data through the structured questionnaire consisting of general characteristics, the number and hours of smartphone usage, and the Smartphone Addiction Proneness Scale (SAPS) from 110 Chinese international students in Korea. The body composition and physical activity, such as the total daily number of steps and consumed calories, were measured. RESULTS: In this study, high-risk smartphone users showed less physical activity, such as the total number of steps taken and the average consumed calories per day. Moreover, their body composition, such as muscle mass and fat mass, was significantly different. Among these factors, the hours of smartphone use revealed the proportional relationship with smartphone addiction (beta = 0.209, p = 0.026), while the average number of walking steps per day showed a significant reverse proportional tendency in participants with smartphone addiction (beta = 0.883, p < 0.001). CONCLUSIONS: Participants with smartphone addiction were less likely to walk for each day. Namely, smartphone addiction may negatively influence physical health by reducing the amount of physical activity, such as walking, resulting in an increase of fat mass and a decrease of muscle mass associated with adverse health consequences. PMID- 26551912 TI - Eating disorder risk, exercise dependence, and body weight dissatisfaction among female nutrition and exercise science university majors. AB - BACKGROUND AND AIMS: Past research has examined eating disorder risk among college students majoring in Nutrition and has suggested an increased risk, while other studies contradict these results. Exercise Science majors, however, have yet to be fully examined regarding their risk for eating disorders and exercise dependence. Based on pressures to fit the image associated with careers related to these two disciplines, research is warranted to examine the potential risk for both eating disorder and exercise dependence. The purpose of this study is to compare eating disorder risk, exercise dependence, and body weight dissatisfaction (BWD) between Nutrition and Exercise Science majors, compared to students outside of these career pathways. METHODS: Participants (n = 89) were divided into three groups based on major; Nutrition majors (NUTR; n = 31), Exercise Science majors (EXSC; n = 30), and other majors (CON; n = 28). Participants were given the EAT-26 questionnaire and the Exercise Dependence Scale. BWD was calculated as the discrepancy between actual BMI and ideal BMI. RESULTS: The majority of participants expressed a desire to weigh less (83%) and EXSC had significantly (p = .03) greater BWD than NUTR. However, there were no significant differences in eating disorder risk or exercise dependence among majors. DISCUSSION AND CONCLUSIONS: This study suggested there was no significant difference in eating disorder risk or exercise dependence between the three groups (NUTR, EXSC, and CON). PMID- 26551914 TI - Galectin-1 Controls the Proliferation and Migration of Liver Sinusoidal Endothelial Cells and Their Interaction With Hepatocarcinoma Cells. AB - Galectin-1 (Gal1), a beta-galactoside-binding protein elevated in hepatocellular carcinoma (HCC), promotes epithelial-mesenchymal transition (EMT) and its expression correlates with HCC growth, invasiveness, and metastasis. During the early stages of HCC, transforming growth factor beta1 (TGF-beta1 ) acts as a tumor suppressor; however in advanced stages, HCC cells lose their cytostatic response to TGF-beta1 and undergo EMT. Here, we investigated the role of Gal1 on liver endothelial cell biology, and the interplay between Gal1 and TGF-beta1 in HCC progression. By Western blot and immunofluorescence, we analyzed Gal1 expression, secretion and localization in HepG2 and HuH-7 human HCC cells, and in SK-HEP-1 human liver sinusoidal endothelial cells (SECs). We used loss-of function and gain-of-function experiments to down- or up-regulate Gal1 expression, respectively, in HepG2 cells. We cultured SK-HEP-1 cells with conditioned media from HCC cells secreting different levels of Gal1, and demonstrated that Gal1 derived from tumor hepatocytes induced its own expression in SECs. Colorimetric and scratch-wound assays revealed that secretion of Gal1 by HCC cells induced SEC proliferation and migration. Moreover, by fluorescence microscopy we demonstrated that Gal1 promoted glycan-dependent heterotypic adhesion of HepG2 cells to SK-HEP-1 SECs. Furthermore, TGF-beta1 induced Gal1 expression and secretion by HCC cells, and promoted HepG2 cell adhesion to SK-HEP 1 SECs through a Gal1-dependent mechanism. Finally, Gal1 modulated HepG2 cell proliferation and sensitivity to TGF-beta1 -induced growth inhibition. Our results suggest that Gal1 and TGF-beta1 might function coordinately within the HCC microenvironment to regulate tumor growth, invasion, metastasis, and angiogenesis. PMID- 26551915 TI - Onsite Substitution Synthesis of Ultrathin Ni Nanofilms Loading Ultrafine Pt Nanoparticles for Hydrogen Evolution. AB - Here, the ultrathin Ni nanofilms loading ultrafine Pt nanoparticles (Ni/Pt nanocomposites) were synthesized by a simple substitution method for the electrocatalysis of hydrogen evolution reaction (HER). First, the ultrathin Ni nanofilms were prepared by using NaBH4 to reduce Ni salt. Then the ultrafine Pt nanoparticles attached on the surface of the ultrathin Ni nanofilms through the onsite substitution reaction between PtCl6(2-) and Ni element. X-ray photoelectron spectroscopy (XPS) experiment confirmed that Ni in Ni/Pt nanocomposites exists in the form of Ni(OH)2. Transmission electro microscope (TEM) study showed that the ultrafine Pt nanoparticles were sufficiently dispersed and loaded at Ni ultrathin nanofilms. The obtained Ni/Pt nanocomposites exhibited superior activity of HER and good stability in acidic media. It obtained 10 and 100 mA/cm(2) with overpotential of only 36 and 115 mV, respectively. The stability experiment of 20,000 s gave nearly negligible current decrease. On the one hand, the ultrathin Ni nanofilms help to disperse and form the ultrafine Pt nanoparticles. On the other hand, the ultrathin Ni nanofilms help to load the ultrafine Pt nanoparticles as catalyst support and immobilize both of them onto the electrode surface because of the high surface free energy of ultrathin nanofilm and the leading high adsorption ability. In addition, Ni itself exhibited somewhat electrocatalytic activity of HER, which contributed to the whole HER electrocatalysis of Ni/Pt nanocomposites. The excellent electrocatalysis may lead to the decreased consumption of expensive Pt and open up new opportunities for applications in hydrogen energy. PMID- 26551916 TI - Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator. AB - IMPORTANCE: Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA. OBJECTIVE: To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA. DESIGN, SETTING, AND PARTICIPANTS: This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period. EXPOSURES: Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke. MAIN OUTCOMES AND MEASURES: Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]). RESULTS: Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16 1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50). CONCLUSIONS AND RELEVANCE: Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy. PMID- 26551917 TI - Morphometric Analysis of Explant Lungs in Cystic Fibrosis. AB - RATIONALE: After repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking. OBJECTIVES: To quantify the involvement of small and large airways in end-stage CF. METHODS: Multidetector computed tomography (MDCT) and micro-CT were applied to 11 air-inflated CF explanted lungs and 7 control lungs to measure, count, and describe the airway and parenchymal abnormalities in end-stage CF lungs. Selected abnormalities were further investigated with thin section histology. MEASUREMENTS AND MAIN RESULTS: On MDCT, CF explanted lungs showed an increased median (interquartile range) number (631 [511-710] vs. 344 [277-349]; P = 0.003) and size of visible airways (cumulative airway diameter 217 cm [209-250] vs. 91 cm [80-105]; P < 0.001) compared with controls. Airway obstruction was seen, starting from generation 6 and increasing to 40 to 50% of airways from generation 9 onward. Micro-CT showed that the total number of terminal bronchioles was decreased (2.9/ml [2.6-4.4] vs. 5.3/ml [4.8-5.7]; P < 0.001); 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced (0.093 mm(2) [0.084-0.123] vs. 0.179 mm(2) [0.140-0.196]; P < 0.001). On micro-CT, 41% of the obstructed airways reopened more distally. This remodeling was confirmed on histological analysis. Parenchymal changes were also seen, mostly in a patchy and peribronchiolar distribution. CONCLUSIONS: Extensive changes of dilatation and obstruction in nearly all airway generations were observed in end-stage CF lung disease. PMID- 26551918 TI - So many options, where do we start? An overview of the care transitions literature. AB - BACKGROUND: Health systems are faced with a large array of transitional care interventions and patient populations to whom such activities might apply. PURPOSE: To summarize the health and utilization effects of transitional care interventions, and to identify common themes about intervention types, patient populations, or settings that modify these effects. DATA SOURCES: PubMed and Cochrane Database of Systematic Reviews (January 1950-May 2014), reference lists, and technical advisors. STUDY SELECTION: Systematic reviews of transitional care interventions that reported hospital readmission as an outcome. DATA EXTRACTION: We extracted transitional care procedures, patient populations, settings, readmissions, and health outcomes. We identified commonalities and compiled a narrative synthesis of emerging themes. DATA SYNTHESIS: Among 10 reviews of mixed patient populations, there was consistent evidence that enhanced discharge planning and hospital-at-home interventions reduced readmissions. Among 7 reviews in specific patient populations, transitional care interventions reduced readmission in patients with congestive heart failure and general medical populations. In general, interventions that reduced readmission addressed multiple aspects of the care transition, extended beyond hospital stay, and had the flexibility to accommodate individual patient needs. There was insufficient evidence on how caregiver involvement, transition to sites other than home, staffing, patient selection practices, or care settings modified intervention effects. CONCLUSIONS: Successful interventions are comprehensive, extend beyond hospital stay, and have the flexibility to respond to individual patient needs. The strength of evidence should be considered low because of heterogeneity in the interventions studied, patient populations, clinical settings, and implementation strategies. PMID- 26551921 TI - Evidence of Different Propofol Pharmacokinetics under Short and Prolonged Infusion Times in Rabbits. AB - Propofol is an anaesthetic widely used in both human beings and animals. However, the characterization of propofol pharmacokinetics (PK) is not well understood when long-term infusions are used. The main objective of this study was to explore the PK behaviour of propofol in a rabbit model during short and prolonged propofol infusions and to develop an internally validated PK model, for propofol dose individualization in the rabbit for future use. Population 1 (P1) was constituted by seven New Zealand rabbits and was used to characterize the PK profile of propofol at short infusions. Animals were anaesthetized with a bolus of 20 mg/kg, followed by an infusion rate of 50 mg/kg/hr of propofol at 1%, which was then maintained for 30 min. A second rabbit population (P2, n = 7) was sedated according to reflexes responses and Index of Consciousness values, for 20 consecutive hours using propofol 2% aiming at characterizing propofol behaviour at long-term infusions. Clinical data and blood samples were collected at specific time-points in both populations. Propofol plasma concentrations were determined by gas chromatography/ion trap mass spectrometry. The NONMEM VII software was used to evaluate the relationships between dose and plasma concentrations. A linear two-compartment model with different central compartment volume and plasma clearance (separately modelled in the two populations) was the one that best described propofol concentrations. The time course of propofol plasma concentrations was well characterized by the PK model developed, which simultaneously accounts for propofol short- and long-term infusions and can be used to optimize future PK studies in rabbits. PMID- 26551920 TI - Negotiating the use of female-initiated HIV prevention methods in a context of gender-based violence: the narrative of rape. AB - Female-initiated methods of HIV prevention are needed to address barriers to HIV prevention rooted in gender inequalities. Understanding the sociocultural context of pre-exposure prophylaxis (PrEP) trials, including gender-based violence, is thus critical. MTN-003C (VOICE-C), a qualitative sub-study of the larger MTN-003 (VOICE) trial, examined sociocultural barriers and facilitators to PrEP amongst women in Johannesburg. We conducted focus-group discussions, in-depth interviews and ethnographic interviews with 102 trial participants, 22 male partners, 17 community advisory board members and 23 community stakeholders. We analysed how discussions of rape are emblematic of the gendered context in which HIV risk occurs. Rape emerged spontaneously in half of discussions with community advisory board members, two-thirds with stakeholders and among one-fifth of interviews/discussions with trial participants. Rape was used to reframe HIV risk as external to women's or partner's behaviour and to justify the importance of PrEP. Our research illustrates how women, in contexts of high levels of sexual violence, may use existing gender inequalities to negotiate PrEP use. This suggests that future interventions should simultaneously address harmful gender attitudes, as well as equip women with alternative means to negotiate product use, in order to more effectively empower women to protect themselves from HIV. PMID- 26551922 TI - Overexpression of mutant dystrophin Dp71[INCREMENT]78-79 stimulates cell proliferation. AB - Dp71 dystrophin is the main DMD gene product expressed in the central nervous system. Experiments using PC12 cells as a neuronal model have shown that Dp71 isoforms are involved in differentiation, adhesion, cell division, and nuclear architecture. To contribute to the knowledge of Dp71 domains function, we previously reported the isolation and partial characterization of the dystrophin Dp71[INCREMENT]78-79 (a mutant that lacks exons 71, 78, and 79), which stimulates the neuronal differentiation of PC12-C11 clone. In this article, we generated a doxycycline (Dox)-inducible expression system in PC12 Tet-On cells (B10 cells) to overexpress and control the transcription of Dp71[INCREMENT]78-79. Western blotting and confocal microscopy showed an increase in the amount of Dp71[INCREMENT]78-79 (217+/-75-fold) with the addition of Dox to growth medium. Cell proliferation assays and morphometric analyses demonstrated that Dp71[INCREMENT]78-79 increases the growth rate of B10 cells and reduces the nerve growth factor-neuronal differentiation. Western blotting analysis revealed an upregulation in the expression of proliferating cell nuclear antigen, focal adhesion kinase, and beta-dystroglycan in B10 cells compared with control cells. Our results show that the inducible expression of Dp71[INCREMENT]78-79 increases the growth rate of PC12 Tet-On cells, suggesting a role of this protein in cell proliferation. PMID- 26551923 TI - Epileptic brain reorganization dynamics on the basis of the probability of connections. AB - Ictal and interictal epileptiform discharges affect brain functional dynamics, but the issue of how they occur is still under debate. The present study evaluated the brain electrical activity that underlies epileptic seizures by focusing analysis on four electroencephalographic time stages around seizure onset. The dynamics of the functional organization of the brain regions at rest, and then immediately before, during, and after, epileptic seizures in a group of five patients diagnosed with intractable temporal epilepsy was examined. The analysis is based on the probability of connections between different brain regions as determined by partial directed coherence. A probability-based graph is constructed for each stage and then the dynamics of reorganization is described using invariant measures on the basis of the graphs obtained. The functional reorganization of brain connectivity is illustrated for each time period, reflecting their temporal variations. The graph method applied proved to be useful in depicting temporal variations in functional brain connectivity because of ictal disruptions in temporal epilepsy, thus providing the possibility of further evaluation of these changes in individual cases to support medical decisions. PMID- 26551924 TI - Effect of Active Workstation on Energy Expenditure and Job Performance: A Systematic Review and Meta-analysis. AB - BACKGROUND: Recently developed active workstation could become a potential means for worksite physical activity and wellness promotion. The aim of this review was to quantitatively examine the effectiveness of active workstation in energy expenditure and job performance. METHODS: The literature search was conducted in 6 databases (PubMed, SPORTDiscuss, Web of Science, ProQuest, ScienceDirect, and Scopuse) for articles published up to February 2014, from which a systematic review and meta-analysis was conducted. RESULTS: The cumulative analysis for EE showed there was significant increase in EE using active workstation [mean effect size (MES): 1.47; 95% confidence interval (CI): 1.22 to 1.72, P < .0001]. Results from job performance indicated 2 findings: (1) active workstation did not affect selective attention, processing speed, speech quality, reading comprehension, interpretation and accuracy of transcription; and (2) it could decrease the efficiency of typing speed (MES: -0.55; CI: -0.88 to -0.21, P < .001) and mouse clicking (MES: -1.10; CI: -1.29 to -0.92, P < .001). CONCLUSION: Active workstation could significantly increase daily PA and be potentially useful in reducing workplace sedentariness. Although some parts of job performance were significantly lower, others were not. As a result there was little effect on real life work productivity if we made a good arrangement of job tasks. PMID- 26551925 TI - TEES 2.2: Biomedical Event Extraction for Diverse Corpora. AB - BACKGROUND: The Turku Event Extraction System (TEES) is a text mining program developed for the extraction of events, complex biomedical relationships, from scientific literature. Based on a graph-generation approach, the system detects events with the use of a rich feature set built via dependency parsing. The TEES system has achieved record performance in several of the shared tasks of its domain, and continues to be used in a variety of biomedical text mining tasks. RESULTS: The TEES system was quickly adapted to the BioNLP'13 Shared Task in order to provide a public baseline for derived systems. An automated approach was developed for learning the underlying annotation rules of event type, allowing immediate adaptation to the various subtasks, and leading to a first place in four out of eight tasks. The system for the automated learning of annotation rules is further enhanced in this paper to the point of requiring no manual adaptation to any of the BioNLP'13 tasks. Further, the scikit-learn machine learning library is integrated into the system, bringing a wide variety of machine learning methods usable with TEES in addition to the default SVM. A scikit-learn ensemble method is also used to analyze the importances of the features in the TEES feature sets. CONCLUSIONS: The TEES system was introduced for the BioNLP'09 Shared Task and has since then demonstrated good performance in several other shared tasks. By applying the current TEES 2.2 system to multiple corpora from these past shared tasks an overarching analysis of the most promising methods and possible pitfalls in the evolving field of biomedical event extraction are presented. PMID- 26551926 TI - Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway. AB - The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 MUg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation induced lung injury, likely through the PKR signaling pathway. PMID- 26551927 TI - A quantum chemical study of the reactivity of acetaminophen (paracetamol) toxic metabolite N-acetyl-p-benzoquinone imine with deoxyguanosine and glutathione. AB - Acetaminophen (APAP) forms some reactive metabolites that can react with DNA. APAP is a potentially genotoxic drug and is classified as a Group 3 drug according to International Agency for Research on Cancer (IARC). One of the possible mechanisms of APAP genotoxicity after long term of use is that its reactive quinone imine (QI) metabolite of acetaminophen (NAPQI), can chemically react with DNA after glutathione (GSH) depletion. A quantum chemical study of the reactions between the NAPQI and deoxyguanosine (dG) or GSH was performed. Activation energies (DeltaG(?)) for the reactions associated with the 1, 4 Michael addition were calculated on the M062X/6-311++G (d,p) level of theory. We modeled the reaction with dG as a multi-step process. The first step is rate limiting (DeltaG(?) = 26.7 kcal/mol) and consists of formation of a C-N bond between the C3 atom of the QI moiety and the N7 atom of dG. The second step involves proton transfer from the C3 moiety to the nitrogen atom of the QI with DeltaG(?) of 13.8 kcal/mol. The depurination reaction that follows has a DeltaG(?) of 25.7 kcal/mol. The calculated DeltaG(?) for the nucleophilic attack of the deprotonated S atom of GSH on the C3 atom of the NAPQI is 12.9 kcal/mol. Therefore, the QI will react with GSH much faster than with DNA. Our study gives mechanistic insight into the genotoxicity of the APAP metabolite and will be useful for estimating the genotoxic potential of existing drugs with a QI moiety. Our results show that clinical application of APAP is safe, while in the case of severely depleted GSH levels APAP should be administered with caution. PMID- 26551928 TI - Synergistic Acid-Promoted Synthesis of Highly Substituted Butenolides via the Annulation of Keto Acids and Tertiary Alcohols. AB - An efficient and practical approach to highly substituted butenolides via the annulation of keto acids and tertiary alcohols is described. The synergistic effect provided by the combination of Lewis and Bronsted acids is crucial to the reaction outcome. A variety of highly substituted butenolides are readily produced in synthetically useful yields. Water is the only waste from the reaction, therefore making it an environmentally benign and atom-economical process for butenolide synthesis. PMID- 26551929 TI - EFFICACY OF THE 20-WEEK CIRCLE OF SECURITY INTERVENTION: CHANGES IN CAREGIVER REFLECTIVE FUNCTIONING, REPRESENTATIONS, AND CHILD ATTACHMENT IN AN AUSTRALIAN CLINICAL SAMPLE. AB - Circle of Security is an attachment theory based intervention that aims to promote secure parent-child attachment relationships. Despite extensive uptake of the approach, there is limited empirical evidence regarding efficacy. The current study examined whether participation in the 20-week Circle of Security intervention resulted in positive caregiver-child relationship change in four domains: caregiver reflective functioning; caregiver representations of the child and the relationship with the child; child attachment security, and attachment disorganization. Archived pre- and postintervention data were analyzed from 83 clinically referred caregiver-child dyads (child age: 13-88 months) who completed the Circle of Security intervention in sequential cohorts and gave permission for their data to be included in the study. Caregivers completed the Circle of Security Interview, and dyads were filmed in the Strange Situation Procedure before and after the intervention. Results supported all four hypotheses: Caregiver reflective functioning, caregiving representations, and level of child attachment security increased after the intervention, and level of attachment disorganization decreased for those with high baseline levels. Those whose scores were least optimal prior to intervention showed the greatest change in all domains. This study adds to the evidence suggesting that the 20-week Circle of Security intervention results in significant relationship improvements for caregivers and their children. PMID- 26551930 TI - High-performance formaldehyde gas-sensors based on three dimensional center hollow ZnO. AB - Three dimensional (3D) center-hollow ZnO architectures assembled by nanoparticles have been successfully fabricated on a large scale via a template-free method using an oil bath. The samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller specific surface area, surface photocurrent and UV-Vis diffuse reflectance spectroscopy. The photoelectric gas-sensing results demonstrated that the 3D porous, center-hollow ZnO structures exhibited excellent sensitivity and good selectivity to formaldehyde under 365 nm light irradiation at room temperature. The gas response to 1 ppm formaldehyde can reach 70%, which is superior to the results reported in the literature, indicating that the 3D center-hollow ZnO architectures are ideal candidate materials for photoelectric gas sensors. The underlying mechanisms responsible for the high sensitivity and selectivity to formaldehyde are discussed, which provide a new pathway for designing novel VOC sensors. Moreover, the facile method presented in this paper has the advantage of low-cost and high-yield, which is suitable for the practical production processes. PMID- 26551932 TI - Development and initial validation of a disease-specific bowel continence questionnaire for inflammatory bowel disease patients: the ICIQ-IBD. AB - BACKGROUND AND AIMS: Faecal incontinence (FI) related to inflammatory bowel disease (IBD) affects up to 74% of patients and is often under-reported in clinical encounters. A previous study found that several important bowel function concerns of patients with IBD are not addressed by existing FI questionnaires, especially differences between symptoms in relapse and remission. We have therefore adapted an existing FI assessment questionnaire specifically for patients with IBD. METHODS: A total of 190 people participated in this study. Phase 1 (development): the initial draft of the new questionnaire was developed from previously collected data and from results of a modified Delphi survey of IBD clinicians; questions were refined through six rounds of cognitive interviewing (n=24). Phase 2 (validation): the final version was tested (n=166) and retested (n=143) 3-4 weeks later. RESULTS: Missing data were minimal (1-4%). Weighted kappa analysis showed moderate-to-good agreement for test-retest data. Factor rotational analysis revealed the relationship of questions with each other. The new questionnaire has two domains: 'Symptoms' and 'Quality of Life', recording remission and relapse scores with simple summary scores for each. An additional 10 stand-alone questions address issues of specific concern to patients with IBD. The questionnaire demonstrates the ability to capture changing symptoms and concerns between remission and relapse. CONCLUSION: The new questionnaire has good content validity and is stable and reliable. Further testing to establish sensitivity to change is needed. The scale can be used by patients, researchers and practitioners to assess severity, fluctuation and impact of IBD-related FI. PMID- 26551931 TI - Isolation and characterization of renal cancer stem cells from patient-derived xenografts. AB - As rapidly developing patient-derived xenografts (PDX) could represent potential sources of cancer stem cells (CSC), we selected and characterized non-cultured PDX cell suspensions from four different renal carcinomas (RCC). Only the cell suspensions from the serial xenografts (PDX-1 and PDX-2) of an undifferentiated RCC (RCC-41) adapted to the selective CSC medium. The cell suspension derived from the original tumor specimen (RCC-41-P-0) did not adapt to the selective medium and strongly expressed CSC-like markers (CD133 and CD105) together with the non-CSC tumor marker E-cadherin. In comparison, PDX-1 and PDX-2 cells exhibited evolution in their phenotype since PDX-1 cells were CD133high/CD105 /Ecadlow and PDX-2 cells were CD133low/CD105-/Ecad-. Both PDX subsets expressed additional stem cell markers (CD146/CD29/OCT4/NANOG/Nestin) but still contained non-CSC tumor cells. Therefore, using different cell sorting strategies, we characterized 3 different putative CSC subsets (RCC-41-PDX-1/CD132+, RCC-41-PDX 2/CD133-/EpCAMlow and RCC-41-PDX-2/CD133+/EpCAMbright). In addition, transcriptomic analysis showed that RCC-41-PDX-2/CD133- over-expressed the pluripotency gene ERBB4, while RCC-41-PDX-2/CD133+ over-expressed several tumor suppressor genes. These three CSC subsets displayed ALDH activity, formed serial spheroids and developed serial tumors in SCID mice, although RCC-41-PDX-1/CD132+ and RCC-41-PDX-2/CD133+ displayed less efficiently the above CSC properties. RCC 41-PDX-1/CD132+ tumors showed vessels of human origin with CSC displaying peri vascular distribution. By contrast, RCC-41-PDX-2 originated tumors exhibiting only vessels of mouse origin without CSC peri-vascular distribution.Altogether, our results indicate that PDX murine microenvironment promotes a continuous redesign of CSC phenotype, unmasking CSC subsets potentially present in a single RCC or generating ex novo different CSC-like subsets. PMID- 26551933 TI - Functional dyspepsia is associated with GNbeta3 C825T and CCK-AR T/C polymorphism. AB - BACKGROUND: A polymorphism (C825T) in G-protein beta polypeptide-3 (GNbeta3) gene alters intracellular signal transduction, which may cause motor or sensory abnormalities in the gastrointestinal tract. Cholecystokinin-A receptor (CCK-AR) gene T/C polymorphism is associated with a defective splicing of the primary transcript of CCK-AR mRNA, which may modulate satiety signal and delay gastric emptying. Therefore, we evaluated the role of these polymorphisms in patients with functional dyspepsia (FD) as compared with healthy controls (HC). PATIENTS AND METHODS: A total of 237 consecutive patients with FD (Rome III) and 250 HC were genotyped for GNbeta3 C825T and CCK-AR T/C polymorphisms (PCR-RFLP). RESULTS: Patients with FD [173 (73%) men, age: 38 +/- 12 years] were comparable with HC [195 (78%) men, age: 37 +/- 12 years] with respect to age and sex. Out of 237 patients, 26 (11%) had epigastric pain syndrome (EPS), 55 (23.2%) had postprandial distress syndrome (PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, TT genotype (associated with increased intracellular signal transduction) of GNbeta3 C825T polymorphism was more common among patients than among HC [26 (11%) vs. 12 (4.8%), P=0.014; odds ratio (OR): 2.47, 95% confidence interval (CI): 1.2-5.1]. CC (variant) genotype of CCK-AR T/C polymorphism was infrequent among patients than among HC [19 (8%) vs. 46 (18.4%), P=0.001; OR: 0.36, 95% CI: 0.19-0.66]. However, these polymorphisms were comparable among patients with different subtypes of FD (P=0.80 and 0.44). CONCLUSION: TT genotype of GNbeta3 C825T is more common among patients with FD than among HC, suggesting that increased signal transduction associated with this genotype may be important in its pathophysiology. However, CCK-AR polymorphism is protective against FD. PMID- 26551934 TI - From Targets to Treatments: Bridging Autoimmune Research to Advance Understanding of Alopecia Areata. AB - Alopecia areata is a common autoimmune skin disease resulting in the loss of hair on the scalp and elsewhere on the body that affects over 146 million people worldwide at some point in their lives. Founded in 1981, the National Alopecia Areata Foundation (NAAF) is a nonprofit organization that supports research to find a cure or acceptable treatment for alopecia areata, supports those with the disease, and educates the public about alopecia areata. NAAF conducts research summits every 2 years that are central to achieving the goals of a major strategic initiative, the Alopecia Areata Treatment Development Program, which are: to accelerate progress toward a safe, effective, affordable treatment or a cure for alopecia areata. These summits have played a key role in transforming the understanding of alopecia areata from largely inflammatory and dermatological perspectives to a focus on the genetic and immunological factors that are now recognized as driving and active determinants of the disease process. PMID- 26551935 TI - Overview of AA and Research Progress: What Have We Learned and Where Are We Headed? AB - During its 25th anniversary year, the National Alopecia Areata Foundation undertook a project to completely re-evaluate their research program and to help focus and direct future directions of alopecia areata research to better meet the goals of people with alopecia areata (AA) and the scientists working to discover mechanisms of disease and better treatments for AA. This project was embodied in four research summits in 2008, 2009, 2010, and 2012, as part of the Foundation's main strategic initiative, the Alopecia Areata Treatment Development Program to accelerate progress toward a viable alopecia areata treatment. The first summit was an evaluation of the progress of AA research in a global sense, with an emphasis on how to use the research programs to bring better treatments to patients. The second summit focused on immunology and how to better understand the autoimmune nature of AA. The third summit focused on developing a clinical research network that could most effectively bring new treatments to patients. The fourth summit consolidated the considerable evidence of the mechanisms of AA, and how these mechanisms could be targeted by modern therapies, many of which were being used effectively in other autoimmune diseases. These four summits laid the foundation for the fifth summit in the series: From Targets to Treatments: Bridging Autoimmune Research to Advance Understanding of Alopecia Areata. PMID- 26551936 TI - Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes. AB - Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the-as yet elusive-key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA. PMID- 26551937 TI - Therapy for Alopecia Areata in Mice by Stimulating the Hair Cycle with Parathyroid Hormone Agonists Linked to a Collagen-Binding Domain. AB - Alopecia areata is a common disorder in which autoimmune destruction of hair follicles results in patchy hair loss. Currently there is no adequate therapy, although immune modulator therapies are currently in development. Parathyroid hormone (PTH) is a hair cycle stimulator which shows promise in treating various forms of alopecia, although its short half-life limits its clinical use. PTH-CBD is a PTH analog which binds collagen, prolonging retention in skin. We tested effects of PTH-CBD in C3H/HeJ-engrafted mice, the animal model for alopecia areata, on hair growth and found that a significant proportion of animals had reduced hair loss (PTH-CBD: 13/21, 62% vs. CONTROL: 3/10, 30%; P<0.01). Histological analysis showed no change in immune response, but there was increased number of anagen hair follicles and increased production of beta catenin, a factor which initiates the anagen phase of the hair cycle. PTH-CBD thus shows promise as a therapy for alopecia areata, either alone or in conjunction with immune modulation therapy. PMID- 26551938 TI - Diphencyprone Treatment of Alopecia Areata: Postulated Mechanism of Action and Prospects for Therapeutic Synergy with RNA Interference. AB - Diphencyprone (DPCP) is a potent topical sensitizing agent that has been used since the late 1970s by physicians for the treatment of alopecia areata (AA), viral warts (human papillomavirus) and cutaneous metastases of melanoma. Although to date the compound is not approved as a drug by the FDA or EMA, physicians have continued to use DPCP because of its proven effects in these dermatological conditions. The use of the drug has been highly variable because of differences in compounding, and as a result, the literature reports vary widely in the concentrations used for sensitization and challenge treatment with DPCP. The efficacy of DPCP has generally been ascribed to immunological reactions by the host. Inducing inflammation with a contact sensitizer is counterintuitive to treating AA, an autoimmune disorder. We have hypothesized that the body's attempt to downregulate the inflammation caused by the contact sensitizer may also ameliorate AA. Studies using microarray and miRNA profiling may provide information about how DPCP induces inflammation in human skin at different times. Gene targets and microRNAs identified through these data may be modulated by an RNA interference approach to enhance DPCP efficacy and response rates. In addition, this approach may result in the discovery and development of drugs that are more potent and selective for the treatment of AA. PMID- 26551939 TI - Mechanisms of LtxA (Leukotoxin), a Potent New Anti-Inflammatory Agent for the Treatment of Alopecia Areata. AB - Alopecia areata is an autoimmune condition where activated, pro-inflammatory white blood cells (WBCs) attack the hair follicles, resulting in hair loss. Migration of these activated WBCs from the blood stream and into the follicle tissue requires interaction between the integrin, lymphocyte function-associated antigen-1 (LFA-1) on WBCs, and ICAM-1 on vascular endothelial cells. High levels of active LFA-1 are uniquely expressed on WBCs that are involved in autoimmune and inflammatory conditions. The natural biologic agent LtxA (Leukothera) preferentially targets and depletes disease activated and malignant WBCs by binding to active LFA-1. The experimental drug has demonstrated significant therapeutic efficacy against autoimmune/inflammatory conditions such as psoriasis and allergic asthma in mouse models for these diseases. In addition, when injected into rodents, rhesus macaques, and dogs, LtxA was demonstrated to be physiologically active, biologically specific, and extremely well-tolerated. LFA 1 is an attractive target for therapy because it is only normally present on WBCs and has been shown to be activated and overexpressed on WBCs that are responsible for autoimmune/inflammatory conditions. PMID- 26551940 TI - Animal Models for Alopecia Areata: What and Where? AB - Disease is not limited to humans. Rather, humans are but another mammal in a continuum, and as such, often share similar if not identical diseases with other mammalian species. Alopecia areata (AA) is such a disease. Natural disease occurs in humans, nonhuman primates, many domestic animals, and laboratory rodents. However, to be useful as models of human disease, affected animals need to be readily available to the research community, closely resemble the human disease, be easy to work with, and provide reproducible data. To date, the laboratory mouse (most if not all of the C3H substrains) and the Dundee experimental bald rat fit these criteria. Manipulations using full-thickness skin grafts or specific immune cell transfers have improved the models. New mouse models that carry a variety of genetic-based immunodeficiencies can now be used to recapitulate the human immune system and allow for human full-thickness skin grafts onto mice to investigate human-specific mechanistic and therapeutic questions. These models are summarized here including where they can currently be obtained from public access repositories. PMID- 26551941 TI - Excavating the Genome: Large-Scale Mutagenesis Screening for the Discovery of New Mouse Models. AB - Technology now exists for rapid screening of mutated laboratory mice to identify phenotypes associated with specific genetic mutations. Large repositories exist for spontaneous mutants and those induced by chemical mutagenesis, many of which have never been fully studied or comprehensively evaluated. To supplement these resources, a variety of techniques have been consolidated in an international effort to create mutations in all known protein coding genes in the mouse. With targeted embryonic stem cell lines now available for almost all protein coding genes and more recently CRISPR/Cas9 technology, large-scale efforts are underway to create further novel mutant mouse strains and to characterize their phenotypes. However, accurate diagnosis of skin, hair, and nail diseases still relies on careful gross and histological analysis, and while not automated to the level of the physiological phenotyping, histopathology still provides the most direct and accurate diagnosis and correlation with human diseases. As a result of these efforts, many new mouse dermatological disease models are being characterized and developed. PMID- 26551942 TI - Integration of the Transcription Factor-Regulated and Epigenetic Mechanisms in the Control of Keratinocyte Differentiation. AB - The epidermal differentiation program is regulated at several levels including signaling pathways, lineage-specific transcription factors, and epigenetic regulators that establish well-coordinated process of terminal differentiation resulting in formation of the epidermal barrier. The epigenetic regulatory machinery operates at several levels including modulation of covalent DNA/histone modifications, as well as through higher-order chromatin remodeling to establish long-range topological interactions between the genes and their enhancer elements. Epigenetic regulators exhibit both activating and repressive effects on chromatin in keratinocytes (KCs): whereas some of them promote terminal differentiation, the others stimulate proliferation of progenitor cells, as well as inhibit premature activation of terminal differentiation-associated genes. Transcription factor-regulated and epigenetic mechanisms are highly connected, and the p63 transcription factor has an important role in the higher-order chromatin remodeling of the KC-specific gene loci via direct control of the genome organizer Satb1 and ATP-dependent chromatin remodeler Brg1. However, additional efforts are required to fully understand the complexity of interactions between distinct transcription factors and epigenetic regulators in the control of KC differentiation. Further understanding of these interactions and their alterations in different pathological skin conditions will help to progress toward the development of novel approaches for the treatment of skin disorders by targeting epigenetic regulators and modulating chromatin organization in KCs. PMID- 26551943 TI - Big Data, Big Opportunities, and Big Challenges. AB - High-throughput assays have begun to revolutionize modern biology and medicine. The advent of cheap next-generation sequencing (NGS) has made it possible to interrogate cells and human populations as never before. Although this has allowed us to investigate the genetics, gene expression, and impacts of the microbiome, there remain both practical and conceptual challenges. These include data handling, storage, and statistical analysis, as well as an inherent problem of the analysis of heterogeneous cell populations. PMID- 26551944 TI - The Use of the Immune Epitope Database to Study Autoimmune Epitope Data Related to Alopecia Areata. AB - The Immune Epitope Database (IEDB) is a repository of published epitope data for infectious diseases, allergy, transplantation and autoimmunity. Herein we provide an introduction to the IEDB search interface, focusing on data related to autoimmune diseases, including alopecia areata (AA). We demonstrate how common questions related can be answered, such as how to search for specific autoantigens, epitope sequences, response types (B- and/or T-cell assays), or host, as well as how to search for epitopes of known major histocompatibility complex restriction and for data related to a specific disease. Our survey of the data found that while as a whole Autoimmunity-specific records represent a significant portion (~30%); epitopes reported for AA are remarkably few, just 23 epitopes from six antigens. This reveals a significant knowledge gap for AA, and suggests that additional mapping of epitopes and identification of novel AA associated autoantigens is warranted. Citing recently published examples, we show how bioinformatic, proteomic, and technological advances make it now increasingly feasible to identify epitopes and novel antigens in human disease. The goal herein was to increase awareness of the IEDB as a free resource for the scientific community and to demonstrate its use in finding (existing) and analyzing (prediction) epitope data. PMID- 26551945 TI - The Need for a Treatment: A Patient's Perspective. AB - Alopecia areata is not a life-threatening disease, but it is absolutely life altering. Alopecia areata can wreak havoc on a person's self-esteem at any age. Since the appearance of my first bald spot more than 35 years ago, millions have been diagnosed with alopecia areata and have had to endure emotional and social difficulties as a result. The scientific community has made tremendous strides in recent years to gain a better understanding of alopecia. Past, current, and planned clinical trials all provide hope to patients and their families that an effective treatment is on the horizon. PMID- 26551946 TI - Current Treatments for Alopecia Areata. AB - Selection of a therapy for a patient with alopecia areata (AA) is frequently based on the age of the patient, disease extent, perhaps disease duration, patient expectations, cost of therapy in terms of time commitment, and financial resources, as well as the results of screening laboratory studies that rule out the presence of other co-morbidities such as anemia, low iron stores, thyroid abnormalities, low vitamin D, or other autoimmune diseases. Although there is currently no cure for AA and no universally proven therapy that induces and sustains remission, many therapies are available which can be of benefit to both affected children and adults. Before selecting a treatment for patients with extensive long-standing AA, a scalp biopsy may provide useful information about the degree of inflammation and follicle differentiation. Recent clinical and translational research observations with the systemic Janus kinase (JAK) inhibitors and interleukin-2 (IL-2) have excited the clinical and AA patient communities and have led to clinical trials, as well as to the off-label use of these more expensive and targeted systemic therapies. PMID- 26551947 TI - ILK Index and Regrowth in Alopecia Areata. AB - There is insufficient data in the literature concerning optimal intralesional kenalog (ILK) dosing for the treatment of alopecia areata (AA). The purpose of this pilot study was to evaluate the utility of using the ratio of ILK received to initial Severity of Alopecia Tool (SALT) score to guide ILK dosing in patients with AA. Using photographic data from patients at baseline and 4-months follow up, hair loss in 15 patients treated with AA was retrospectively graded using the SALT scores. The ILK received/initial SALT score (ILK index) was calculated for each patient, and the mean ILK index for patients who experienced significant (>=50%) and suboptimal (<50%) hair regrowth at 4 months follow-up were compared. Patients who experienced suboptimal hair regrowth had a lower ILK index on average than patients who experienced significant improvement. Although the difference did not meet significance (<0.1), the trend suggests that the ILK index, a novel calculation, may be a useful tool for guiding ILK dosing in the treatment of AA. PMID- 26551948 TI - Clinical Efficacy of Diphenylcyclopropenone in Alopecia Areata: Retrospective Data Analysis of 50 Patients. AB - Diphenylcyclopropenone (DPCP) is widely considered the most effective topical immunotherapy for refractory or extensive alopecia areata (AA), but questions regarding how long to try DPCP therapy before terminating and what factors are prognostic of therapeutic success still remain unanswered. In this retrospective study of 50 AA patients, we evaluated DPCP efficacy and identified patient factors predictive of therapeutic success/failure. The median duration of DPCP treatment was 3 years, with 47% patients experiencing their first regrowth in the first 6 months of DPCP therapy, 20% between 6 months-1 year, and 8% between 1-2 years. In our study, treatment success, defined as ?50% terminal hair regrowth, was reached in 71% of alopecia totalis patients and in 56% of alopecia universalis patients. Three factors were statistically significant predictors of poor treatment outcome-extent of hair loss before DPCP treatment, history of thyroid disease, and extent of body hair involvement. Relapse was observed in 44% of patients and significantly associated with history of thyroid disease. Common side effects were itching, rash, and local lymphadenopathy. The results of this study support our belief that DPCP therapy is a viable treatment option, can be successfully accomplished at home, and should not be terminated before 2 years. PMID- 26551949 TI - Alopecia Areata Registry Accomplishments. PMID- 26551950 TI - Eosinophilic Esophagitis: Another Atopy-Related Alopecia Areata Trigger? AB - Alopecia areata (AA) is associated with atopy in 10-22% of patients, twice the prevalence in the general population. Patients can present with concomitant atopic dermatitis, hay fever, asthma, and even allergies to dust mites. In many cases, severity and flares of these atopic diatheses correlate with severity of AA. Herein we present a patient with AA affected by contemporaneous eosinophilic esophagitis (EoE). EoE is a recently recognized allergic disorder, mediated by eosiniphils and histamine. It is characterized by esophageal dysfunction and intraepithelial microabscesses. We propose that EoE be considered as a condition falling within the realm of atopic diseases, and a potential trigger of AA in affected patients. PMID- 26551951 TI - Prevalence of Comorbid Conditions and Sun-Induced Skin Cancers in Patients with Alopecia Areata. AB - Alopecia areata is a multifactorial autoimmune disease causing non-scarring hair loss. Recent genome-wide association studies have pointed to connections between alopecia areata and other autoimmune disorders. Research of clinical conditions positively and negatively associated with alopecia areata is crucial for discovering the pathological mechanisms of disease and further treatment options. PMID- 26551952 TI - Development of Uniform Protocol for Alopecia Areata Clinical Trials. AB - Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies. PMID- 26551953 TI - Industry Perspective on Alopecia Areata. AB - Recent advances in our understanding of the autoimmune basis of alopecia areata provide an opportunity to create novel effective pharmaceutical interventions. The current lack of approved therapies for alopecia areata presents a high unmet medical need, as well as a potentially attractive market opportunity. From an industry perspective, achieving clinical proof of concept (PoC) gates investments into larger approval studies. Recent investigator-initiated experience suggests that it may be possible to demonstrate rigorous PoC for new therapies in an attractive time frame with relatively fewer patients than were believed necessary in the past. However, the lack of prior regulatory approval precedent for pharmaceuticals to treat alopecia areata poses significant development challenges, and early interaction with the FDA and other stakeholders will be critically important in evaluating the path to approval and reimbursement for new treatments for this indication. This paper presents a brief industry perspective on the potential development of new alopecia areata therapeutics. PMID- 26551954 TI - Interfacial challenges in solid-state Li ion batteries. PMID- 26551955 TI - Platinum Metal-Free Catalysts for Selective Soft Oxidative Methane -> Ethylene Coupling. Scope and Mechanistic Observations. AB - Using abundant soft oxidants, a high methane-to-ethylene conversion might be achievable due to the low thermodynamic driving force for over-oxidation. Here we report on the oxidative coupling of methane by gaseous S2 (SOCM). The catalytic properties of Pd/Fe3O4 are compared with those of Fe3O4, and it is found that high ethylene selectivities can be achieved without noble metals; conversion and selectivity on Fe3O4 are stable for at least 48 h at SOCM conditions. SOCM data for 10 oxides are compared, and ethylene selectivities as high as 33% are found; the C2H4/C2H6 ratios of 9-12 observed at the highest S2 conversions are significantly higher than the C2H4/C2H6 ratios usually found in the CH4 coupling with O2. Complementary in-detail analytical studies show that, on Mg, Zr, Sm, W, and La catalysts, which strongly coke during the reaction, lower ethylene selectivities are observed than on Fe, Ti, and Cr catalysts, which only coke to a minor extent. Further catalyst-dependent changes during SOCM in surface area, surface composition, and partial conversion to oxysulfides and sulfides are discussed. Evidence concerning the reaction mechanism is obtained taking into account the selectivity for the different reaction products versus the contact time. CH4 coupling proceeds non-oxidatively with the evolution of H2 on some catalysts, and evidence is presented that C2H4 and C2H2 formation occur via C2H6 and C2H4 dehydrogenation, respectively. PMID- 26551956 TI - Practice Trends in the Use of Extracorporeal Treatments for Poisoning in Four Countries. AB - Extracorporeal treatments (ECTRs) such as hemodialysis (HD), enhance the elimination of a small number of toxins. Changes in overdose trends, prescribing practices, antidotes, and dialysis techniques may alter the indications and rates of ECTR use over time. This study analyzed trends in ECTR for poisonings in four countries. A retrospective study of national poison center databases from the United States, Denmark, United Kingdom, and five regional databases within Canada was performed. All cases of patients receiving an ECTR were included. ECTR cases were totalled annually and reported as annual rates per 100,000 exposures with stratification per types of ECTR and toxins. The data collection varied by countries. United States, 1985-2014; United Kingdom, 2011-2013; Denmark, 2005 2014, and regions of Canada as follows: Alberta, 1991-2015; Saskatchewan, 2001 2015; Nova Scotia-PEI, 2006-2015; Quebec, 2008-2014; Ontario-Manitoba, 2009-2015; British Columbia, 2012-2015. During the study period, the total number of ECTRs and rates per 100,000 exposures, respectively, were: United States, 40,258 and 65.7; United Kingdom, 343 and 232.6; Denmark, 616 and 305.5; Canada, 2709 and 177.5; case rates increased over time for the United States, Denmark, and Canada, but decreased in the United Kingdom. Across the United States and Denmark, HD was the preferred modality used. Toxins for which ECTR was most often used were: United States, ethylene glycol; Canada, methanol; United Kingdom, ethylene glycol; Denmark, salicylates. A high number of ECTRs were performed for atypical toxins such as acetaminophen and benzodiazepines. These data demonstrate a growing use of HD for poisoning with significant regional variations in the overall rates and indications. PMID- 26551959 TI - Association Between Glutamate Blockade and Fatigue in Patients With Multiple Sclerosis. PMID- 26551960 TI - Non-N-Methyl-D-Aspartate Receptor Antibody Encephalitis With Cerebellitis With Associated Ovarian Teratoma. PMID- 26551961 TI - Novel Variant of Miller Fisher Syndrome Occurring With Tumor Necrosis Factor alpha Antagonist Therapy. PMID- 26551962 TI - Use of Descriptive Terms in Medical Records. PMID- 26551963 TI - Use of Descriptive Terms in Medical Records. PMID- 26551964 TI - Use of Descriptive Terms in Medical Records-Reply. PMID- 26551966 TI - In Memoriam: Frank A. Rubino, MD. PMID- 26551967 TI - An automated cell viability quantification method for low-resolution confocal images of closely packed cells based on a modified gradient flow tracking algorithm. AB - Fluorescent-based live/dead labelling combined with fluorescent microscopy is one of the widely used and reliable methods for assessment of cell viability. This method is, however, not quantitative. Many image-processing methods have been proposed for cell quantification in an image. Among all these methods, several of them are capable of quantifying the number of cells in high-resolution images with closely packed cells. However, no method has addressed the quantification of the number of cells in low-resolution images containing closely packed cells with variable sizes. This paper presents a novel method for automatic quantification of live/dead cells in 2D fluorescent low-resolution images containing closely packed cells with variable sizes using a mean shift-based gradient flow tracking. Accuracy and performance of the method was tested on growth plate confocal images. Experimental results show that our algorithm has a better performance in comparison to other methods used in similar detection conditions. PMID- 26551968 TI - Monitoring testosterone levels in testosterone-treated men. AB - Dose adjustment with transdermal testosterone preparations should recognize the variability of serum total testosterone levels between applications and over the course of 24 h. Dose adjustments are also made difficult by between-laboratory assay variability. Low SHBG with obesity and diabetes lowers the total testosterone level, and free or bioavailable testosterone may prove to be a better choice for monitoring the progress and dosing of testosterone-treated men with adult onset hypogonadism. PMID- 26551970 TI - Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl] 8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT2 Receptor Agonist. AB - Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1 [(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3 g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans. PMID- 26551969 TI - Highly Elastic and Conductive Human-Based Protein Hybrid Hydrogels. AB - A highly elastic hybrid hydrogel of methacryloyl-substituted recombinant human tropoelastin (MeTro) and graphene oxide (GO) nanoparticles are developed. The synergistic effect of these two materials significantly enhances both ultimate strain (250%), reversible rotation (9700 degrees ), and the fracture energy (38.8 +/- 0.8 J m(-2) ) in the hybrid network. Furthermore, improved electrical signal propagation and subsequent contraction of the muscles connected by hybrid hydrogels are observed in ex vivo tests. PMID- 26551972 TI - Hyperostosis frontalis interna presenting as depression and parkinsonism in an older woman. PMID- 26551973 TI - Effect of Marangoni Flows on the Shape of Thin Sessile Droplets Evaporating into Air. AB - Freely receding evaporating sessile droplets of perfectly wetting liquids, for which the observed finite contact angles are attributed to evaporation, are studied with a Mach-Zehnder interferometer. The experimentally obtained droplet shapes are found to depart, under some conditions, from the classical macroscopic static profile of a sessile droplet. The observed deviations (or the absence thereof) are explained in terms of a Marangoni flow due to evaporation-induced thermal gradients along the liquid-air interface. When such a Marangoni effect is strong, the experimental profiles exhibit a maximum of the slope at a certain distance from the contact line. In this case, the axisymmetric flow is directed from the contact line to the apex (along the liquid-air interface), hence delivering more liquid to the center of the droplet and making it appear inflated. These findings are quantitatively confirmed by predictions of a lubrication model accounting for the impact of the Marangoni effect on the droplet shape. PMID- 26551971 TI - Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function. AB - Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition. PMID- 26551974 TI - Major Adverse Events and Relationship to Nil per Os Status in Pediatric Sedation/Anesthesia Outside the Operating Room: A Report of the Pediatric Sedation Research Consortium. AB - BACKGROUND: Studies that have attempted to define the incidence of aspiration or pulmonary complications during sedation/anesthesia of children with respect to nil per os (NPO) status or other factors are difficult because of the relatively infrequent rate of these complications. METHODS: The Pediatric Sedation Research Consortium consists of 42 participating institutions with elective sedation services that submit consecutive patient encounter information to a central database. The authors evaluated aspiration episodes and a combined outcome of major adverse events (defined as aspiration, death, cardiac arrest, or unplanned hospital admission) with respect to NPO status, American Society of Anesthesiologists physical status, age, propofol use, procedure types, and urgency of the procedure. RESULTS: A total of 139,142 procedural sedation/anesthesia encounters were collected between September 2, 2007 and November 9, 2011. There were 0 deaths, 10 aspirations, and 75 major complications. NPO status was known for 107,947 patients, of whom 25,401 (23.5 %) were not NPO. Aspiration occurred in 8 of 82,546 (0.97 events per 10,000) versus 2 of 25,401 (0.79 events per 10,000) patients who were NPO and not NPO, respectively (odds ratio, 0.81; 95% CI, 0.08 to 4.08; P = 0.79). Major complications occurred in 46 of 82,546 (5.57 events per 10,000) versus 15 of 25,401 (5.91 events per 10,000) (odds ratio, 1.06; 95% CI, 0.55 to 1.93; P = 0.88). Multivariate adjustment did not appreciably impact the effect of NPO status. CONCLUSIONS: The analysis suggests that aspiration is uncommon. NPO status for liquids and solids is not an independent predictor of major complications or aspiration in this sedation/anesthesia data set. PMID- 26551975 TI - Violent Death Rates: The US Compared with Other High-income OECD Countries, 2010. AB - BACKGROUND: Violent death is a serious problem in the United States. Previous research showing US rates of violent death compared with other high-income countries used data that are more than a decade old. METHODS: We examined 2010 mortality data obtained from the World Health Organization for populous, high income countries (n = 23). Death rates per 100,000 population were calculated for each country and for the aggregation of all non-US countries overall and by age and sex. Tests of significance were performed using Poisson and negative binomial regressions. RESULTS: US homicide rates were 7.0 times higher than in other high income countries, driven by a gun homicide rate that was 25.2 times higher. For 15- to 24-year-olds, the gun homicide rate in the United States was 49.0 times higher. Firearm-related suicide rates were 8.0 times higher in the United States, but the overall suicide rates were average. Unintentional firearm deaths were 6.2 times higher in the United States. The overall firearm death rate in the United States from all causes was 10.0 times higher. Ninety percent of women, 91% of children aged 0 to 14 years, 92% of youth aged 15 to 24 years, and 82% of all people killed by firearms were from the United States. CONCLUSIONS: The United States has an enormous firearm problem compared with other high-income countries, with higher rates of homicide and firearm-related suicide. Compared with 2003 estimates, the US firearm death rate remains unchanged while firearm death rates in other countries decreased. Thus, the already high relative rates of firearm homicide, firearm suicide, and unintentional firearm death in the United States compared with other high-income countries increased between 2003 and 2010. PMID- 26551976 TI - High Lung Cancer Incidence in Heavy Smokers Following Hospitalization due to Pneumonia. AB - INTRODUCTION: The rate of lung cancer incidence following pneumonia in heavy smokers is unknown. Heavy smokers hospitalized due to community-acquired pneumonia might be at high risk for subsequent lung cancer. The primary objective of this study was to determine lung cancer incidence in this high-risk population. PATIENTS AND METHODS: This was a single-center, retrospective cohort study that included heavy smokers hospitalized due to community-acquired pneumonia between January 1, 2007 and December 31, 2011 in Beilinson hospital, a large community hospital and tertiary center. Patients were identified by International Classification of Diseases, Ninth Revision coding from the hospital's registry. Two physicians reviewed every patient's medical file for patient demographics, smoking history, lung cancer risk factors, and anatomical location of pneumonia. Data were cross-checked with the database at the national cancer registry for new diagnoses of cancer. RESULTS: There were 381 admissions for community-acquired pneumonia included in the final analysis. Thirty-one cases (8.14%; 95% confidence interval [CI], 5.9%-11.2%) of lung cancer were diagnosed during the first year after hospitalization. Lung cancer incidence was significantly higher in patients who had upper-lobe pneumonia (23.8%; 95% CI, 14.9%-40%). Lung cancer was located within the lobe involved by the pneumonia in 75.8% of patients. CONCLUSIONS: A high lung cancer rate was found in heavy smokers admitted due to community-acquired pneumonia. The association was especially strong for patients with upper-lobe pneumonia. Screening with chest computed tomography should be strongly considered for these patients. PMID- 26551978 TI - The 'Springer Gene': Combating Familial Obesity with Technology and Exercise. PMID- 26551977 TI - Assessing the Caprini Score for Risk Assessment of Venous Thromboembolism in Hospitalized Medical Patients. AB - BACKGROUND: The optimal approach to assess risk of venous thromboembolism in hospitalized medical patients is unknown. We examined how well the Caprini risk assessment model predicts venous thromboembolism in hospitalized medical patients. METHODS: Between January 2011 and March 2014, venous thromboembolism events and risk factors were collected from non-intensive care unit medical patients hospitalized in facilities across Michigan. After calculation of the Caprini score for each patient, mixed logistic spline regression was used to determine the predicted probabilities of 90-day venous thromboembolism by receipt of pharmacologic prophylaxis across the Caprini risk continuum. RESULTS: A total of 670 (1.05%) of 63,548 eligible patients experienced a venous thromboembolism event within 90 days of hospital admission. The mean Caprini risk score was 4.94 (range, 0-28). Predictive modeling revealed a consistent linear increase in venous thromboembolism for Caprini scores between 1 and 10; estimates beyond a score of 10 were unstable. Receipt of pharmacologic prophylaxis resulted in a modest decrease in venous thromboembolism risk (odds ratio, 0.85; 95% confidence interval, 0.72-0.99; P = .04). However, the low overall incidence of venous thromboembolism led to large estimates of numbers needed to treat to prevent a single venous thromboembolism event. A Caprini cut-point demonstrating clear benefit of prophylaxis was not detected. CONCLUSIONS: Although a linear association between the Caprini risk assessment model and the risk of venous thromboembolism was noted, an extremely low incidence of venous thromboembolism events in non-intensive care unit medical patients was observed. The Caprini risk assessment model was unable to identify a subset of medical patients who benefit from pharmacologic prophylaxis. PMID- 26551979 TI - A Rare Cause of Multiple Bone Lesions: Metastasis or Not? PMID- 26551980 TI - Systemic Lupus Erythematosus in an Elderly Man Diagnosed by the Presence of Pericardial Fluid Lupus Erythematosus Cells. PMID- 26551981 TI - Uptake of Influenza Vaccination and Missed Opportunities Among Adults with High Risk Conditions, United States, 2013. AB - BACKGROUND: Since 1960, the Advisory Committee on Immunization Practices has recommended influenza vaccination for adults with certain high-risk conditions because of increased risk for complications from influenza infection. We assessed national influenza vaccination among persons ages 18-64 years with high-risk conditions. METHODS: We analyzed data from the 2012 and 2013 National Health Interview Survey. The Kaplan-Meier survival analysis procedure was used to estimate the cumulative proportion of influenza vaccination among adults ages 18 64 years with high-risk conditions. Potential missed opportunities for influenza vaccination were also evaluated. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with vaccination. RESULTS: Overall, 39.9 million adults ages 18-64 years (18.9%) had at least one high-risk condition. For adults ages 18-64 years with high-risk conditions, overall influenza vaccination coverage was 49.5%. Coverage among adults 50-64 years of age was significantly higher compared with those ages 18-49 years (59.3% vs 39.0%; P <.05). Among adults ages 18-64 years, coverage was 46.2% for those with chronic lung diseases, 50.5% for those with heart disease, 58.0% for those with diabetes, 62.5% for those with renal disease, and 56.4% for those with cancer. Overall, 90.1% reported at least one visit to a health care setting where vaccination could have been provided. Among adults ages 18-64 years with high-risk conditions, older age, being female, Hispanic ethnicity or Asian race, having one or more physician visits, a regular physician for health care, health insurance, and having ever received pneumococcal vaccination were independently associated with a higher likelihood of influenza vaccination. Being widowed/divorced/separated or never married and not being employed were independently associated with a lower likelihood of influenza vaccination. CONCLUSIONS: Influenza vaccination coverage varies substantially by age and high risk conditions but remains low. Approximately 50% of those with high-risk conditions remain unvaccinated. Health care providers should ensure they routinely assess influenza vaccination status, and recommend and offer vaccines to those with high-risk conditions. PMID- 26551983 TI - Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient. PMID- 26551982 TI - Trends in Coronary Atherosclerosis: A Tale of Two Population Subgroups. AB - BACKGROUND: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined. The present investigation of coronary artery disease trends for the period 1995 through 2012 was prompted by a desire for more detailed examination of more recent coronary artery disease trends in light of reports that the epidemics of obesity and diabetes have slowed and are perhaps ending. METHODS: This population based series of cross-sectional investigations identified all Olmsted County, Minnesota residents aged 16-64 years who died 1995 through 2012 (N = 2931). For decedents with nonnatural manner of death, pathology reports were reviewed for grade of atherosclerosis assigned each major epicardial coronary artery. Using logistic regression, we estimated calendar-year trends in grade (unadjusted and age- and sex-adjusted) for each artery, initially as an ordinal measure (range, 0 4); then, based on evidence of nonproportional odds, as a dichotomous variable (any atherosclerosis, yes/no) and as an ordinal measure for persons with atherosclerosis (range, 1-4). RESULTS: Of 474 nonnatural deaths, 453 (96%) were autopsied; 426 (90%) had coronary stenosis graded. In the ordinal-logistic model for trends in coronary artery disease grade (range, 0-4), the proportional odds assumption did not hold. In subsequent analysis as a dichotomous outcome (grades 0 vs 1-4), each artery exhibited a significant temporal decline in the proportion with any atherosclerosis. Conversely, for subjects with coronary artery disease grade 1-4, age- and sex-adjusted ordinal regression revealed no change over time in 2 arteries and statistically significant temporal increases in severity in 2 arteries. CONCLUSIONS: Findings suggest that efforts to prevent coronary artery disease onset have been relatively successful. However, statistically significant increases in the grade of atherosclerosis in 2 arteries among persons with coronary artery disease may be indicative of a major public health challenge. PMID- 26551984 TI - Home Treatment of Deep Venous Thrombosis According to Comorbid Conditions. AB - BACKGROUND: Cautious exploration of the safety of home treatment of deep venous thrombosis has been recommended by many. Our goal was to identify categories of patients with deep venous thrombosis who typically are hospitalized, and categories frequently treated at home. METHODS: The Nationwide Emergency Department Sample and the Nationwide Inpatient Sample, 2007-2012, were used to determine the number of patients seen in emergency departments throughout the US with deep venous thrombosis and no diagnosis of pulmonary embolism, the proportion of such patients hospitalized according to comorbid conditions and age, the proportion discharged early (<=2 days), and charges for hospitalization and emergency department visits. RESULTS: From 2007-2012, home treatment was selected for 905,152 of 2,671,452 (33.9%) patients with deep venous thrombosis. Home treatment was more frequent in those with no comorbid conditions than with comorbid conditions, 58.0% compared with 15.5% (P <.0001). Early discharge (<=2 days) was in 23.9% with no comorbid conditions, compared with 12.8% with comorbid conditions. Among patients aged 18-50 years, home treatment was selected in 62.9% with no comorbid conditions, compared with 24.2% with comorbid conditions (P <.0001). Among hospitalized patients with no comorbid conditions, 40.7% were aged 18-50 years. Their charges for hospitalization in 2012 were $494 million. CONCLUSION: Patients aged 50 years or younger with deep venous thrombosis and no comorbid conditions appear to be a group that can be targeted for more frequent home treatment, which would save millions of dollars. PMID- 26551985 TI - Should Statin Therapy Be Guided by Cardiovascular Risk Models? PMID- 26551986 TI - 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis? AB - BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether percent low-density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known. METHODS: Patients in the Treating to New Targets (TNT), Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials (patient-level data) randomized to a statin arm (atorvastatin 80 mg/10 mg or simvastatin 20 mg) were chosen. Patients were divided into groups based on attained LDL-C levels (<=70 vs >70 mg/dL) and percent LDL-C reduction (>=50% vs <50%). Primary outcome was major cardiovascular event defined as death due to coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1 statin dose; Step 2 add attained LDL-C levels (continuous variable); Step 3 add percent LDL-C reduction (continuous variable). Model 2: Steps 2 and 3 were reversed. RESULTS: Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (global chi square increased from 3.64 to 26.1 to 47.5; P <.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (global chi-square increased from 3.64 to 47.5 to 47.5; P <.0001 and .94, respectively). Among patients with attained LDL-C <=70 mg/dL, those with percent LDL-C reduction of <50% had a significantly higher risk of primary outcome (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.16-1.97; P = .002) and stroke (HR, 2.07; 95% CI, 1.46-2.93; P <.0001) and a numerically higher risk of death (HR, 1.37; 95% CI, 0.98-1.90; P = .06) when compared with the group with percent LDL-C reduction of >=50%. CONCLUSIONS: In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction. PMID- 26551988 TI - A meta-analysis of XPC Lys939Gln polymorphism and melanoma susceptibility. AB - BACKGROUND: It has been reported that polymorphisms of XPC Lys939Gln may affect the risk of melanom. However, the results have been inconsistent.We performed a comprehensive meta-analysis to determine the association between XPC Lys939Gln polymorphism and melanoma susceptibility. METHODS: Based on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between XPC Lys939Gln polymorphism and melanoma risk. RESULTS: A total of 4631 cases and 5111 controls in studies were included in this meta-analysis. All studies were conducted in Caucasian populations. Allele model (Gln vs. Lys: P = 0.22; OR = 1.07, 95% CI = 0.96-1.18), and homozygous model (Gln/Gln vs. Lys/Lys: P = 0.66; OR = 1.03, 95% CI = 0.91-1.17) did not show increased risk of developing melanoma. Similarly, dominant model Gln/Gln and Gln/Lys vs. Lys/Lys: P = 0.07; OR = 1.17, 95% CI = 0.99-1.40) and recessive model (Gln/Gln vs. Gln/Lys and Lys/Lys: P = 0.67; OR = 1.03, 95% CI = 0.90-1.19) failed to show increased risk of developing melanoma. CONCLUSION: Our pooled data suggest that there was no evidence for a major role of XPC Lys939Gln polymorphism in the pathogenesis of melanoma. PMID- 26551987 TI - Evaluation of direct phloroglucinolysis and colorimetric depolymerization assays and their applicability for determining condensed tannins in grape marc. AB - To determine the optimum methods for determining condensed tannin (CT) content in grape marc, butanol-hydrochloric acid assays and phloroglucinolysis were adapted for use, applied to a range of grape marc types, and the methods compared. Porter's assay (butanol-HCl) was found to give unreliable results due to nonlinear color responses to grape skin and seed tannin concentrations, whereas the modification to include acetone (Grabber's assay) overcame this. Differences between skin and seed tannin responses highlighted the need to adequately select the correct grape tannin standard, and the formation of pH-dependent color was accounted for through acidification of blank samples. For phloroglucinolysis, the inability to remove highly bound tannins from cell wall material was highlighted, although a measure of tannins remaining post-phloroglucinolysis (Grabber's assay) showed a trend with the level of exposure to oxidative storage or processing conditions. The comparison of CT concentrations from phloroglucinolysis and Grabber's assay gave poor correlation coefficients. PMID- 26551989 TI - Classification of Parkinson's Disease Gait Using Spatial-Temporal Gait Features. AB - Quantitative gait assessment is important in diagnosis and management of Parkinson's disease (PD); however, gait characteristics of a cohort are dispersed by patient physical properties including age, height, body mass, and gender, as well as walking speed, which may limit capacity to discern some pathological features. The aim of this study was twofold. First, to use a multiple regression normalization strategy that accounts for subject age, height, body mass, gender, and self-selected walking speed to identify differences in spatial-temporal gait features between PD patients and controls; and second, to evaluate the effectiveness of machine learning strategies in classifying PD gait after gait normalization. Spatial-temporal gait data during self-selected walking were obtained from 23 PD patients and 26 aged-matched controls. Data were normalized using standard dimensionless equations and multiple regression normalization. Machine learning strategies were then employed to classify PD gait using the raw gait data, data normalized using dimensionless equations, and data normalized using the multiple regression approach. After normalizing data using the dimensionless equations, only stride length, step length, and double support time were significantly different between PD patients and controls (p < 0.05); however, normalizing data using the multiple regression method revealed significant differences in stride length, cadence, stance time, and double support time. Random Forest resulted in a PD classification accuracy of 92.6% after normalizing gait data using the multiple regression approach, compared to 80.4% (support vector machine) and 86.2% (kernel Fisher discriminant) using raw data and data normalized using dimensionless equations, respectively. Our multiple regression normalization approach will assist in diagnosis and treatment of PD using spatial-temporal gait data. PMID- 26551990 TI - Streptomyces wadayamensis MppP Is a Pyridoxal 5'-Phosphate-Dependent L-Arginine alpha-Deaminase, gamma-Hydroxylase in the Enduracididine Biosynthetic Pathway. AB - L-Enduracididine (L-End) is a nonproteinogenic amino acid found in a number of bioactive peptides, including the antibiotics teixobactin, enduracidin, and mannopeptimycin. The potent activity of these compounds against antibiotic resistant pathogens like MRSA and their novel mode of action have garnered considerable interest for the development of these peptides into clinically relevant antibiotics. This goal has been hampered, at least in part, by the fact that L-End is difficult to synthesize and not currently commercially available. We have begun to elucidate the biosynthetic pathway of this unusual building block. In mannopeptimycin-producing strains, like Streptomyces wadayamensis, L End is produced from L-Arg by the action of three enzymes: MppP, MppQ, and MppR. Herein, we report the structural and functional characterization of MppP. This pyridoxal 5'-phosphate (PLP)-dependent enzyme was predicted to be a fold type I aminotransferase on the basis of sequence analysis. We show that MppP is actually the first example of a PLP-dependent hydroxylase that catalyzes a reaction of L Arg with dioxygen to yield a mixture of 2-oxo-4-hydroxy-5-guanidinovaleric acid and 2-oxo-5-guanidinovaleric acid in a 1.7:1 ratio. The structure of MppP with PLP bound to the catalytic lysine residue (Lys221) shows that, while the tertiary structure is very similar to those of the well-studied aminotransferases, there are differences in the arrangement of active site residues around the cofactor that likely account for the unusual activity of this enzyme. The structure of MppP with the substrate analogue D-Arg bound shows how the enzyme binds its substrate and indicates why D-Arg is not a substrate. On the basis of this work and previous work with MppR, we propose a plausible biosynthetic scheme for L End. PMID- 26551991 TI - Electronic Cigarette Use and Respiratory Symptoms in Chinese Adolescents in Hong Kong. PMID- 26551992 TI - Ghrelin Receptor Ligands Reaching Clinical Trials: From Peptides to Peptidomimetics; from Agonists to Antagonists. AB - In the recent decades, great progress has been made in the development of ghrelin receptor ligands. The discovery of the first in vitro only active peptide growth hormone secretagogue derived from Met-enkephalin was the foundation for later discoveries of the receptor and the endogenous ligand ghrelin. Since then, the scope of peptides, peptidomimetics, and small-molecules targeting the ghrelin receptor, GHS-R1a, has expanded dramatically. Numerous agonists have been tested in animals and several in humans, and a handful have progressed to clinical trials for indications such as growth hormone release, gastric emptying, and cachexia. However, with the exception of the approval of GHRP-2 for diagnostic purposes in Japan, none of the candidates have been successfully introduced into the market. More recently, the attention of researchers has been concentrated on developing antagonists and inverse agonists for pharmacological treatment of the ever-expanding obese and overweight population. In this review, we describe the development of GHS-R1a targeting agonists, antagonists, and inverse agonists. We focus on current and completed clinical trials and the therapeutic potential of currently available ligands. PMID- 26551993 TI - A Call to Arms: Radial Artery Access for Percutaneous Coronary Intervention. PMID- 26551994 TI - Satellite RNAs and Satellite Viruses. AB - Satellite RNAs and satellite viruses are extraviral components that can affect either the pathogenicity, the accumulation, or both of their associated viruses while themselves being dependent on the associated viruses as helper viruses for their infection. Most of these satellite RNAs are noncoding RNAs, and in many cases, have been shown to alter the interaction of their helper viruses with their hosts. In only a few cases have the functions of these satellite RNAs in such interactions been studied in detail. In particular, work on the satellite RNAs of Cucumber mosaic virus and Turnip crinkle virus have provided novel insights into RNAs functioning as noncoding RNAs. These effects are described and potential roles for satellite RNAs in the processes involved in symptom intensification or attenuation are discussed. In most cases, models describing these roles involve some aspect of RNA silencing or its suppression, either directly or indirectly involving the particular satellite RNA. PMID- 26551995 TI - Patterns of hypnotic response, revisited. AB - It has long been speculated that there are discrete patterns of responsiveness to hypnotic suggestions, perhaps paralleling the factor structure of hypnotizability. An earlier study by Brenneman and Kihlstrom (1986), employing cluster analysis, found evidence for 12 such profiles. A new study by Terhune (2015), employing latent profile analysis, found evidence for three such patterns among highly hypnotizable subjects, and a fourth comprising subjects of medium hypnotizability. Some differences between the two studies are described. Convincing identification of discrete "types" of high hypnotizability, such as dissociative and nondissociative, may require a larger dataset than is currently available, but also data pertaining directly to divisions in conscious awareness and experienced involuntariness. PMID- 26551996 TI - Perceptual confidence demonstrates trial-by-trial insight into the precision of audio-visual timing encoding. AB - Peoples' subjective feelings of confidence typically correlate positively with objective measures of task performance, even when no performance feedback is provided. This relationship has seldom been investigated in the field of human time perception. Here we find a positive relationship between the precision of human timing perception and decisional confidence. We first demonstrate that subjective audio-visual timing judgements are more precise when people report a high, as opposed to a low, level of confidence. We then find that this relationship is more likely to result from variance in sensory timing estimates than the application of variable decision criteria, as the relationship held when we adopted a measure of timing sensitivity designed to limit the influence of subjective criteria. Our results suggest analyses of timing perception and associated decisional confidence reflect the trial-by-trial variability with which timing has been encoded. PMID- 26551997 TI - Induced systemic listeriosis in Alectoris chukar chicks: clinical, histopathological and microbiological findings. AB - 1. Systemic listeriosis was induced in 14-d-old Chukar partridge chicks, Alectoris chukar, by intravenous injection of a suspension containing 10(6) cfu/ml of viable Listeria monocytogenes organisms to study the course of infection. 2. Septicaemic and encephalitic forms of listeriosis were observed in all birds. Infection resulted in a fever response 8-h post-inoculation. Disease rapidly developed over a 24-h period with decreased activity, lethargy, ruffled feathers, huddling, listlessness, inability to stand, wing droop, decreased feed and water consumption, growth depression, neural disturbances and finally death. Gross and histopathological changes were observed in the myocardium, proventriculus, gizzard, intestine, pancreas, kidney, liver, spleen, lung, meninges and joints. 3. The diversity of these clinical signs and lesions suggests a high susceptibility of Chukar partridge chicks to systemic listeriosis. PMID- 26551998 TI - Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease. AB - BACKGROUND: Sleep disturbances (SDs) are common in patients with all forms of dementia. However, most studies focus on Alzheimer's disease (AD) and less is known about the prevalence and characteristics of SD in dementia with Lewy bodies (DLB). OBJECTIVE: The aims of this cross-sectional study were: (1) to examine the frequency of SD in DLB versus AD; (2) to compare patients with and without SD with regard to relevant clinical variables, and (3) to investigate the associations between SD and medication use. METHODS: Patients with a first-time diagnosis of probable or possible DLB or AD were selected from the Dementia Study of Western Norway and recruited from clinics for old age psychiatry from 2010 until the end of 2013. RESULTS: In all, 123 (55.7%) subjects with dementia suffered from at least one SD. Insomnia was present in 77 (34.8%), and 34 (20.7%) patients had probable REM-sleep behaviour disorder (RBD). All SDs were also significantly more frequent in patients with DLB than in AD, and DLB patients also more often had several co-occurring SDs. The presence of any SD was associated with more neuropsychiatric symptoms, higher morbidity, more parkinsonian symptoms and excessive daytime sleepiness. Antiparkinsonian medication was used more often in RBD, restless leg syndrome (RLS) and periodic limb movements, and benzodiazepines were also common in RLS. CONCLUSIONS: Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB. PMID- 26551999 TI - ABCs of SLEEPING: A review of the evidence behind pediatric sleep practice recommendations. AB - The ABCs of SLEEPING mnemonic was developed to serve as an organizing framework for common pediatric sleep recommendations. The mnemonic stands for 1) age appropriate bedtimes and wake-times with consistency, 2) schedules and routines, 3) location, 4) exercise and diet, 5) no electronics in the bedroom or before bed, 6) positivity 7) independence when falling asleep and 8) needs of child met during the day, 9) equal great sleep. This review examines the empirical evidence behind the practices and recommendations captured by the ABCs of SLEEPING mnemonic for children aged 1 to 12. A search was conducted of key electronic databases (PubMed, PsycINFO, CINAHL, & EMBASE) to identify English articles that included the concepts of sleep, insomnia, and/or bedtime. 77 articles were eligible for inclusion and were coded to extract key details and findings regarding the relations between sleep practices identified in the ABCs of SLEEPING mnemonic and sleep outcomes. Findings provided preliminary support for many of the recommendations that are commonly made to families regarding healthy sleep practices. However, more robust investigations are needed to better understand the causal contributions of healthy sleep practices to the onset and maintenance of children's sleep problems. PMID- 26552001 TI - Novel CD8(+) cytotoxic T cell epitopes in bovine leukemia virus with cattle. AB - Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T cell leukemia virus (HTLV). The cytotoxic T lymphocyte (CTL) plays a key role in suppressing the progression of disease caused by BLV. T and B cell epitopes in BLV have been studied, but CD8(+) CTL epitopes remain poorly understood. We used a library of 115 synthetic peptides covering the entirety of the Env proteins (gp51 and gp30), the Gag proteins (p15, p24, and p12), and the Tax protein of BLV to identify 11 novel CD8(+) T cell epitopes (gp51N5, gp51N11, gp51N12, gp30N5, gp30N6, gp30N8, gp30N16, tax16, tax18, tax19, and tax20) in four calves experimentally infected with BLV. The number of CD8(+) T cell epitopes that could be identified in each calf correlated with the BLV proviral load. Interestingly, among the 11 epitopes identified, only gp51N11 was capable of inducing CD8(+) T cell-mediated cytotoxicity in all four calves, but it is not a suitable vaccine target because it shows a high degree of polymorphism according to the Wu-Kabat variability index. By contrast, no CTL epitopes were identified from the Gag structural protein. In addition, several epitopes were obtained from gp30 and Tax, indicating that cellular immunity against BLV is strongly targeted to these proteins. CD8(+) CTL epitopes from gp30 and Tax were less polymorphic than epitopes from. Indeed, peptides tax16, tax18, tax19, and tax20 include a leucine-rich activation domain that encompasses a transcriptional activation domain, and the gp30N16 peptide contains a proline rich region that interacts with a protein tyrosine phosphatase SHP1 to regulate B cell activation. Moreover, at least one CD8(+) CTL epitope derived from gp30 was identified in each of the four calves. These results indicate that BLV gp30 may be the best candidate for the development of a BLV vaccine. PMID- 26552000 TI - Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice. AB - Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette-Guerin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development. PMID- 26552002 TI - Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey. AB - BACKGROUND: Serious adverse events (SAEs) in clinical trials require reporting within 24h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience. METHODS: Members of the clinical advisory forum of experts (CAFE), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine. RESULTS: There were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p=0.0075; and maternal immunisation p=0.045). Amongst study investigators (n=43) this phenomenon was observed for three of the four scenarios: (JIA p=0.0236; developmental delay following infant immunisation p=0.0266; and developmental delay after maternal immunisation p=0.0495). CONCLUSIONS: SAE causality assessment is inconsistent amongst study investigators and can be influenced by the classification systems available to them. There is a pressing need for SAE classification systems to be standardised across study protocols. PMID- 26552004 TI - A Serendipitous Rendezvous with a Four-Center Two-Electron Bonded Intermediate in the Aerial Oxidation of Hydrazine. AB - Oxidation by dioxygen has a rich repertoire of mechanistic intricacies. Herein, we report a hitherto unknown paradigm of dioxygen activation reaction which propagates through a four center two electron (4c-2e) bound species. Using static DFT and ab initio quantum chemical techniques we have unraveled the oxidation pathway for hydrazine and its methylated analogues by dioxygen which involves formation of this unconventional 4c-2e bonded species en route to the oxidation products. Inconvertible evidence in favor of such an unprecedented dioxygen activation route is provided by capturing the events of formation of the 4c-2e species in aqueous phase for hydrazine and its congeners and the experimentally observed products from the respective 4c-2e species, like H2O2 and N2H2 , diazene in the case of hydrazine using Car-Parrinello molecular dynamics simulations. PMID- 26552003 TI - RT-qPCR-based microneutralization assay for human cytomegalovirus using fibroblasts and epithelial cells. AB - Human cytomegalovirus (HCMV) is a leading cause of congenital infection that can result in serious disabilities in affected children. To facilitate HCMV vaccine development, a microscale neutralization assay based on reverse transcription quantitative PCR (RT-qPCR) was developed to quantify HCMV-neutralizing antibodies. Our approach relies on the generation of crude lysates from virus infected cells that are amenable to direct analysis by RT-qPCR, thereby circumventing rate-limiting procedures associated with sample RNA extraction and purification. By serial passaging of the laboratory HCMV strain AD169 in epithelial cells (ARPE-19), a revertant virus with restored epithelial cell tropism, designated AD169(wt131), was obtained. AD169 and AD169(wt131) were evaluated in both epithelial cells (ARPE-19) and fibroblasts (MRC-5) by one-step RT-qPCR targeting the immediate-early gene IE1 transcript of HCMV. Expression kinetics indicated that RT-qPCR assessment could be conducted as early as 6h post infection. Human serum samples (n=30) from healthy donors were tested for HCMV specific IgG using a commercially available ELISA and for HCMV-neutralizing activity using our RT-qPCR-based neutralization assay. In agreement with the ELISA results, higher neutralizing activity was observed in the HCMV IgG seropositive group when compared with the HCMV IgG seronegative group. In addition, HCMV IgG seropositive human sera exhibited higher neutralizing titers using epithelial cells compared with using fibroblasts (geometric mean titers of 344 and 8 in ARPE-19 cells and MRC-5 cells, respectively). Our assay was robust to variation in input virus dose. In addition, a simple lysis buffer containing a non-ionic detergent was successfully demonstrated to be a less costly alternative to commercial reagents for cell-lysate preparation. Thus, our rapid HCMV neutralization assay may be a straightforward and flexible high-throughput tool for measuring antibody responses induced by vaccination and natural infection. PMID- 26552005 TI - High throughput determination of cleaning solutions to prevent the fouling of an anion exchange resin. AB - Effective cleaning of chromatography resin is required to prevent fouling and maximize the number of processing cycles which can be achieved. Optimization of resin cleaning procedures, however, can lead to prohibitive material, labor, and time requirements, even when using milliliter scale chromatography columns. In this work, high throughput (HT) techniques were used to evaluate cleaning agents for a monoclonal antibody (mAb) polishing step utilizing Fractogel((r)) EMD TMAE HiCap (M) anion exchange (AEX) resin. For this particular mAb feed stream, the AEX resin could not be fully restored with traditional NaCl and NaOH cleaning solutions, resulting in a loss of impurity capacity with resin cycling. Miniaturized microliter scale chromatography columns and an automated liquid handling system (LHS) were employed to evaluate various experimental cleaning conditions. Cleaning agents were monitored for their ability to maintain resin impurity capacity over multiple processing cycles by analyzing the flowthrough material for turbidity and high molecular weight (HMW) content. HT experiments indicated that a 167 mM acetic acid strip solution followed by a 0.5 M NaOH, 2 M NaCl sanitization provided approximately 90% cleaning improvement over solutions containing solely NaCl and/or NaOH. Results from the microliter scale HT experiments were confirmed in subsequent evaluations at the milliliter scale. These results identify cleaning agents which may restore resin performance for applications involving fouling species in ion exchange systems. In addition, this work demonstrates the use of miniaturized columns operated with an automated LHS for HT evaluation of chromatographic cleaning procedures, effectively decreasing material requirements while simultaneously increasing throughput. Biotechnol. Bioeng. 2016;113: 1251-1259. (c) 2015 Wiley Periodicals, Inc. PMID- 26552006 TI - Accelerating PS model-based dynamic cardiac MRI using compressed sensing. AB - High spatiotemporal resolution MRI is a challenging topic in dynamic MRI field. Partial separability (PS) model has been successfully applied to dynamic cardiac MRI by exploiting data redundancy. However, the model requires substantial preprocessing data to accurately estimate the model parameters before image reconstruction. Since compressed sensing (CS) is a potential technique to accelerate MRI by reducing the number of acquired data, the combination of PS and CS, named as Stepped-SparsePS, was introduced to accelerate the preprocessing data acquisition of PS in this work. The proposed Stepped-SparsePS method sequentially reconstructs a set of aliased dynamic images in each channel based on PS model and then the final dynamic images from the aliased images using CS. The results from numerical simulations and in vivo experiments demonstrate that Stepped-SparsePS could significantly reduce data acquisition time while preserving high spatiotemporal resolution. PMID- 26552007 TI - Continuous or Interrupted Chest Compressions for Cardiac Arrest. PMID- 26552008 TI - A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. AB - The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations. PMID- 26552010 TI - Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats. AB - Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. PMID- 26552009 TI - SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. AB - Human cancer genome sequencing has recently revealed that genes that encode subunits of SWI/SNF chromatin remodeling complexes are frequently mutated across a wide variety of cancers, and several subunits of the complex have been shown to have bona fide tumor suppressor activity. However, whether mutations in SWI/SNF subunits result in shared dependencies is unknown. Here we show that EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is essential in all tested cancer cell lines and xenografts harboring mutations of the SWI/SNF subunits ARID1A, PBRM1, and SMARCA4, which are several of the most frequently mutated SWI/SNF subunits in human cancer, but that co-occurrence of a Ras pathway mutation is correlated with abrogation of this dependence. Notably, we demonstrate that SWI/SNF-mutant cancer cells are primarily dependent on a non catalytic role of EZH2 in the stabilization of the PRC2 complex, and that they are only partially dependent on EZH2 histone methyltransferase activity. These results not only reveal a shared dependency of cancers with genetic alterations in SWI/SNF subunits, but also suggest that EZH2 enzymatic inhibitors now in clinical development may not fully suppress the oncogenic activity of EZH2. PMID- 26552011 TI - Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels. AB - Diabetics suffer from a higher risk of cognitive decline. cAMP response element binding protein (CREB) is a transcription factor associated with memory and synaptic plasticity. Here, we investigated the molecular changes in the hippocampus correlated with diabetes associated cognitive decline (DACD) from a CREB-centered perspective in a rat model of type 2 diabetes. Furthermore, we tested the therapeutic effect of rolipram on DACD. High-fat diet and low-dose streptozocin were adopted to induce diabetes in SD rats. Results show that supplementation with rolipram for 23 days (0.5mg/kg, once a day) improved the performance of diabetic rats in Morris water navigation task with increased level of CREB, brain-derived neurotrophic factor (BDNF), and Arc protein in the hippocampus. Rolipram, acting as an inhibitor of PDE4, was found to repair the imbalance in the CREB/BDNF/Arc pathway. This study may provide important insights into the mechanisms underlying DACD and provide new therapeutic targets for clinical treatment. PMID- 26552012 TI - Chromatin remodeling gene EZH2 involved in the genetic etiology of autism in Chinese Han population. AB - Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. Epigenetic factors play a critical role in the etiology of ASD. Enhancer of zest homolog 2 (EZH2), which encodes a histone methyltransferase, plays an important role in the process of chromatin remodeling during neurodevelopment. Further, EZH2 is located in chromosome 7q35-36, which is one of the linkage regions for autism. However, the genetic relationship between autism and EZH2 remains unclear. To investigate the association between EZH2 and autism in Chinese Han population, we performed a family-based association study between autism and three tagged single nucleotide polymorphisms (SNPs) that covered 95.4% of the whole region of EZH2. In the discovery cohort of 239 trios, two SNPs (rs740949 and rs6464926) showed a significant association with autism. To decrease false positive results, we expanded the sample size to 427 trios. A SNP (rs6464926) was significantly associated with autism even after Bonferroni correction (p=0.008). Haplotype G-T (rs740949 and rs6464926) was a risk factor for autism (Z=2.655, p=0.008, Global p=0.024). In silico function prediction for SNPs indicated that these two SNPs might be regulatory SNPs. Expression pattern of EZH2 showed that it is highly expressed in human embryonic brains. In conclusion, our findings demonstrate that EZH2 might contribute to the genetic etiology of autism in Chinese Han population. PMID- 26552013 TI - Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders. AB - Previous studies have indicated that the altered composition of polyunsaturated fatty acids (PUFAs) might contribute to the pathophysiology of autism spectrum disorder (ASD). We examined the relationship between the plasma fatty acid levels, expressed as MUg/ml, and the plasma levels of biomarkers of AA-related signaling mediators, such as ceruloplasmin, transferrin and superoxide dismutase, and assessed the behavioral symptoms of 30 individuals with ASD (mean age, 13.6 +/- 4.3 years old) compared with 20 age- and gender-matched normal controls (mean age, 13.2 +/- 5.4 years old) using Aberrant Behavior Checklists (ABC). The plasma levels of EPA and the plasma ratios of EPA/AA were significantly higher, while the plasma levels of AA and metabolites, such as 5,8,11,14-eicosatetraenoic acid, adrenic acid, and ceruloplasmin (Cp), were significantly lower in the 30 individuals with ASD compared with the 20 normal controls. The ABC scores were significantly increased in the ASD group compared with those of the control group. Thus, the results of the present study revealed that reduced plasma levels of AA and metabolites in association with high plasma EPA/AA ratios might down regulate AA-related signaling mediators, such as Cp. Subsequently, reduced plasma Cp levels might reduce the protective capacity for brain damage, resulting in the pathophysiology underlying the behavioral symptoms in individuals with ASD. These findings suggest that reduced plasma AA levels may downregulate Cp. PMID- 26552014 TI - Migration as a social determinant of health for irregular migrants: Israel as case study. AB - More than 150,000 irregular migrants reside in Israel, yet data regarding their utilization of and perceived barriers to health care services are limited. Drawing on semi-structured interviews conducted with 35 irregular migrant adults between January and September 2012, this article analyzes the role of migration as a social determinant of health for irregular migrants, and especially asylum seekers. We analyze two kinds of barriers faced by migrants when they attempt to access health care services: barriers resulting directly from their migration status, and barriers that are common among low-income communities but exacerbated by this status. Migration-related barriers included a lack of clear or consistent legislation; the threat of deportation; the inability to obtain work permits and resulting poverty and harsh living and working conditions; and discrimination. Barriers exacerbated by migrant status included prohibitive cost; poor and confusing organization of services; language barriers; perceived low quality of care; and social isolation. These findings support recent arguments that migrant status itself constitutes a social determinant of health that can intersect with other determinants to adversely affect health care access and health outcomes. Findings suggest that any meaningful effort to improve migrants' health will depend on the willingness of clinicians, public health officials, and policymakers to address the complex array of upstream political and socio economic factors that affect migrants' health rather than focusing on narrower questions of access to health care. PMID- 26552015 TI - Trade-offs and resource breadth processes as drivers of performance and specificity in a host-parasite system: a new integrative hypothesis. AB - One of the unresolved issues in the ecology of parasites is the relationship between host specificity and performance. Previous studies tested this relationship in different systems and obtained all possible outcomes. This led to the proposal of two hypotheses to explain conflicting results: the trade-off and resource breadth hypotheses, which are treated as mutually exclusive in the literature and were corroborated by different studies. In the present study, we used an extensive database on avian malaria from Brazil and combined analyses based on specificity indices and network theory, in order to test which of those hypotheses might best explain our model system. Contrary to our expectations, there was no correlation between specificity and prevalence, which contradicts both hypotheses. In addition, we detected a strong modular structure in our host parasite network and found that its modules were not composed of geographically close, but of phylogenetically close, host species. Based on our results, we reached the conclusion that trade-off and resource breadth hypotheses are not really mutually exclusive. As a conceptual solution we propose "The Integrative Hypothesis of Parasite Specialization", a novel theoretical model that explains the contradictory results found in our study and reported to date in the literature. PMID- 26552016 TI - Genotypic variation in host response to infection affects parasite reproductive rate. AB - Parasite fitness is largely influenced by a variation in host response due to the host's genetic background. Here we investigated the impact of host genotype on pathogen success in the snail vector of its castrating parasite, Schistosoma mansoni. We infected five inbred lines of Biomphalaria glabrata with two infection doses and followed their growth, reproductive output and parasite production throughout the course of infection. There was no difference in resistance to infection among inbred lines, but lines varied in their responses to infection and the numbers of parasites produced. Snails did not compensate for castration by increasing their fecundity during the early phase of infection (fecundity compensation). However, some lines were able to delay parasite shedding for up to 30 weeks, thus prolonging reproduction before the onset of castration. Here we propose this strategy as a novel defense against castrating pathogens in snails. Gigantism, a predicted outcome of castration due to energy reallocation, occurred early in infection (<15 weeks) and was not universal among the snail lines. Lines that did not show gigantism were also characterised by a high parasite production rate and low survivorship, perhaps indicating energy reallocation into parasite production and costly immune defense. We observed no differences in total parasite production among lines throughout the entire course of infection, although lines differed in their parasite reproductive rate. The average rate of parasite production varied among lines from 1300 to 2450 cercariae within a single 2h shedding period, resulting in a total production of 6981-29,509 cercariae over the lifetime of a single snail. Regardless of genetic background, snail size was a strong predictor of parasite reproduction: each millimetre increase in snail size at the time of the first shed resulted in up to 3500 more cercariae over the lifetime of the snail. The results of this study provide a detailed picture of variation in hosts' responses to infection and the resulting impacts on parasite fitness, further defining the intricacies of snail schistosome compatibility. PMID- 26552017 TI - Facilitating psychosexual adjustment for women undergoing pelvic radiotherapy: pilot of a novel patient psycho-educational resource. AB - PURPOSE: This pilot study aimed to obtain feedback on the feasibility, safety and acceptability of a psychosexual rehabilitation booklet developed for women undergoing pelvic radiation therapy (PRT) and to explore women's sexual, informational and supportive care needs post-PRT rehabilitation. METHODS: Twenty women treated with PRT for gynaecological or anorectal cancer within the last 5 years, who had received vaginal dilators, provided feedback on the format, content and utility of the booklet and discussed their post-treatment information needs, via a semi-structured phone interview. Women completed standardized (HADS, IES-R) and study-specific scales to characterize psychological status of the sample and to assess participants' booklet knowledge and feedback, respectively. RESULTS: The booklet was perceived as very helpful, informative and not distressing, providing additional information to that discussed with clinicians. After reading the booklet, women had good understanding of strategies to reduce the sexual impact of PRT. Many women reported that discussion of sexuality was often avoided during consultations, despite them experiencing distressing sexual experiences and difficulties post-PRT. CONCLUSIONS: This novel resource which addresses an important component of post-pelvic radiation care appears acceptable and highly valued. Findings have highlighted a need for sexual health communication training for clinicians who treat this population so that they can initiate conversations about vaginal health and sexual health in an informed and comfortable manner. The impact of the revised booklet on psychosexual and clinical outcomes is being evaluated in a multicentre RCT. PMID- 26552018 TI - Synthesis of raloxifene-chitosan conjugate: A novel chitosan derivative as a potential targeting vehicle. AB - Chitosan is a biocompatible, non-toxic and biodegradable biopolymer. Due to the presence of functional groups on its surface, it can be modified and used as a carrier in targeted drug/gene delivery systems. In this study, raloxifene (a selective estrogen receptor ligand) was conjugated to chitosan using different methods. The conjugates were investigated by means of FTIR, TGA and physical properties assessments. Cell viability was evaluated by XTT assay. FTIR and TGA results confirmed that the conjugation between chitosan and raloxifene occurred more efficiently when trimethyl chitosan in the presence of triethylamine and excess amount of linker was used. XTT assay on MCF-7 cell line illustrated that more than 80% of cells were viable after 24h exposure to selected molecules. These findings confirm that the conjugation of raloxifene-chitosan can occur successfully using special synthesis condition and this novel chitosan derivative can be introduced as a potential drug/gene targeting agent. PMID- 26552019 TI - Temperature dependent rapid annealing effect induces amorphous aggregation of human serum albumin. AB - This study represents an analysis of the thermal aggregation of human serum albumin (HSA) induced by novel rosin modified compounds. The aggregation process causes conformational alterations in the secondary and tertiary structures of the proteins. The conversion of globular protein to amorphous aggregates was carried out by spectroscopic, calorimetric and microscopic techniques to investigate the factors that are responsible for the structural, conformational and morphological alteration in the protein. Our outcome results show that the aggregation of HSA was dependent on the hydrophobicity, charge and temperature, because the formation of amorphous aggregates occurs in the presence of a novel cationic rosin compound, quaternary amine of rosin diethylaminoethyl ester (QRMAE), at 40 degrees C and pH 7.4 (but at 25 degrees C on similar pH value, there was no evidence of aggregate formation). In addition, the parent compound of QRMAE, i.e., abietic acid, and other derivatives such as nonionic rosin compounds [(RMPEG-750) and (RMA-MPEG-750)] do not shows the aggregating property. This work provides precise and necessary information that aid in the understanding the effects of rosin derivative compounds on HSA. This study also restrains important information for athletes, health providers, pharmaceutical companies, industries, and soft drink-processing companies. PMID- 26552020 TI - A comparison of eugenol and menthol on encapsulation characteristics with water soluble quaternized beta-cyclodextrin grafted chitosan. AB - Two guest molecules (eugenol and (-)-menthol) were investigated on inclusion complex formation with water-soluble quaternized beta-CD grafted with chitosan (QCD-g-CS). The inclusion complexes were prepared at varying mole ratios between eugenol or (-)-menthol and beta-CD (substituted on QCD-g-CS) by a conventional shaking method and obtained as solid powder by freeze-drying process. The results showed that encapsulation efficiency %EE decreased with increasing of initial eugenol or (-)-menthol loading whereas %loading increased with increasing of initial eugenol or (-)-menthol loading. The results indicated that inclusion complex formation between eugenol and QCD-g-CS was more favorable than that of ( )-menthol. To clarify this mechanism, molecular dynamics simulations were performed to explore their binding energy, solvation energy and total free energy of those complexes. It was found that the total free energy (DeltaG) of eugenol and (-)-menthol against QCD-g-CS (mole ratio of 1) in water-explicit system were 2108.91 kJ/mol and -344.45 kJ/mol, respectively. Moreover, molecular dynamic simulation of eugenol absorbed on surface QCD-g-CS (-205.73 kJ/mol) was shown to have a higher negative value than that of (-)-menthol on QCD-gCS (3182.31 kJ/mol). Furthermore, the release characteristics of the encapsulated powder were also investigated in simulated saliva pH 6.8 at 32 degrees C. The results suggested that (-)-menthol had higher release rate from the complexes than eugenol. In all cases, the release characteristics for those guest molecules could be characterized by the limited-diffusion kinetics. PMID- 26552021 TI - Intermittent hypoxia induces disturbances in craniofacial growth and defects in craniofacial morphology. AB - OBJECTIVES: To investigate intermittent hypoxia (IH) induced changes in craniofacial morphology and bone mineral density (BMD) in the mandible of growing rats. DESIGN: Seven-week-old male Sprague-Dawley rats were exposed to IH for 4 days or 3 weeks. Sham-operated rats simultaneously breathed room air. Lateral and transverse cephalometric radiographs of the craniofacial region were obtained, and the linear distances between cephalometric landmarks were statistically analyzed. BMD and bone microstructure of the mandible were evaluated using micro computed tomography (micro-CT). RESULTS: Cephalometric analyses demonstrated that exposure to IH only in the two groups for 3 weeks decreased the size of the mandibular and viscerocranial bones, but not that of the neurocranial bones, in early adolescent rats. These findings are consistent with upper airway narrowing and obstructive sleep apnea (OSA). Micro-CT showed that IH increased the BMD in the cancellous bone of the mandibular condyle and the inter-radicular alveolar bone in the mandibular first molar (M1) region. CONCLUSIONS: This study is the first to identify growth retardation of the craniofacial bones in an animal model of sleep apnea. Notably, 3 weeks of IH can induce multiple changes in the bones around the upper airway in pubertal rats, which can enhance upper airway narrowing and the development of OSA. The reproducibility of these results supports the validity and usefulness of this model. These findings also emphasize the critical importance of morphometric evaluation of patients with OSA. PMID- 26552022 TI - Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer. AB - AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized. PMID- 26552024 TI - [Clinical aspects of congenital maxillofacial deformities]. AB - The cleft lip and palate deformity is one of the most common type of congenital abnormalities. The aim of this paper is to summarise the literature knowledge about cleft lip and/or palate. The authors review and discuss international literature data on the prevention, genetic and environmental predisposing factors, anatomical and embryological features, as well as pre- and post-natal diagnosis and treatment of these deformities. The aetiology is multifactorial, driven by both genetic and environmental factors which lead to multifaceted phenotypes and clinical features of these malformations. The lack of the multidisciplinary knowledge about prenatal diagnosis, prevention, genetic aspects and treatment strategy could result in serious diagnostic errors, hence clinical teamwork is critically important to solve the problems of this pathology. Only the professional teamwork and multidisciplinary cooperation can guarantee the optimal level of health care and better quality of life for these patients and their families. PMID- 26552023 TI - Inhibition of anandamide hydrolysis dampens the neuroendocrine response to stress in neonatal rats subjected to suboptimal rearing conditions. AB - Exposure to stress during early development can exert profound effects on the maturation of the neuroendocrine stress axis. The endocannabinoid (ECB) system has recently surfaced as a fundamental component of the neuroendocrine stress response; however, the effect of early-life stress on neonatal ECB signaling and the capacity to which ECB enhancement may modulate neonatal stress responses is relatively unknown. The present study assessed whether exposure to early-life stress in the form of limited access to nesting/bedding material (LB) from postnatal (PND) day 2 to 9 alters neuroendocrine activity and hypothalamic ECB content in neonatal rats challenged with a novel immobilization stressor. Furthermore, we examined whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of anandamide (AEA) affects neuroendocrine responses in PND10 pups as a function of rearing conditions. Neonatal rats showed a robust increase in corticosterone (CORT) and adrenocorticotropin hormone (ACTH) secretion in response to immobilization stress, which was significantly blunted in pups reared in LB conditions. Accordingly, LB pups exhibited reduced stress-induced Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, with no significant differences in hypothalamic ECB content. Administration of the FAAH inhibitor URB597 (0.3 mg/kg, ip) 90 min prior to immobilization stress significantly dampened stress-induced CORT release, but only in pups reared in LB conditions. These results suggest that rearing in restricted bedding conditions dampens the neuroendocrine response to stress, while augmenting AEA mitigates stress-induced alterations in glucocorticoid secretion preferentially in pups subjected to early-life stress. PMID- 26552025 TI - [Clinical features of patients with juvenile and adult dermatomyositis]. AB - INTRODUCTION: Juvenile and adult dermatomysitis are chronic, immune-mediated inflammatory myopathies characterized by progressive proximal muscle weakness and typical skin symptoms. AIM: To compare the symptoms, laboratory and serological findings, treatment and disease course in children and adults suffering from dermatomyositis. METHOD: In this retrospective study, juvenile and adult dermatomyositis groups were formed. There were 27 patients with juvenile dermatomyositis (mean age, 8.7 years; mean follow-up time: 104.6 months) and 30 adult patients (mean age, 50.3; mean follow-up time: 58.1 months). RESULTS: In patients with juvenile dermatomyositis, treatment with intravenous immunoglobulin and cyclosporine A were more frequent as compared to adult patients. Acute onset of the disease was more frequent in adult patients than in those with juvenile disease. In children symptoms of the disease developed gradually. CONCLUSIONS: The findings confirm previously published data showing that there are differences between juvenile and adult patients with dermatomyositis. The authors recommend to follow the patients regularly after reaching remission to avoid bad patient compliance and decrease the number and severity of relapses. PMID- 26552026 TI - [Objective assessment of transfusion-related knowledge of nurses using modern test theory]. AB - INTRODUCTION: Clinical practice requires knowledge of health professionals for the application of problem solving of different tasks in various clinical settings. Therefore, a set of reliable measurement tools is required to assess various components of the professional knowledge including factual knowledge, skills and competence as outcomes of nursing education and training. Traditional questionnaires and test methods do not allow the measurement of these characteristics properly, as these tools typically provide overall scores without relevant insight into areas in which nurses perform well, and those where their knowledge and/or skills should be improved substantially. AIM: The aim of this nationwide survey conducted among nurses between November 2014 and February 2015 was to determine how the teaching/training objectives have been achieved in the nurses' transfusion practice. The authors attempted to exceed the capabilities of classical test theory and acquire a detailed picture about what the nurses know about transfusion therapy and how they are involved and behave in routine clinical practice. METHOD: The knowledge and skills of 657 participants were assessed using a validated instrument consisting of a set of questions covering every aspects of transfusion therapy. The answers to these items were evaluated on a binary (good or bad) scale. Recorded answers of the participants were analysed using hierarchical cluster analysis and item response theory tools such as the one-parametric Rasch model suitable for dichotomous data. Data analysis was performed with the SPSS program and the ltm module of the R statistical program. RESULTS: The paper presents the distribution of correct and incorrect answers to various questions about transfusion therapy along with the corresponding logit values and odds ratios, respectively. The characteristic curves of each item were determined on the basis of the number of correct answers that have been recorded. These curves highlight which questions were answered easily and which items were found harder to answer by the nurses who participated in the survey. In addition to the separate analysis of individual questions, a set of response patterns is also presented which shows how frequently the nurses responded correctly to different combinations (sub-sets) of questions. On the whole, nurses exhibited medium level performance in terms of knowledge and skills required for efficient and safe transfusion practice. CONCLUSIONS: Objective and reliable measurement of the level of acquired knowledge is a key requirement in nursing education. This paper, which demonstrates the use of cluster analysis and item response theory for the assessment of transfusion-related knowledge of nurses, focuses on this issue for the first time in nursing research. The results of this survey have revealed substantial limitations and deficiencies both in knowledge and skills of nurses which need to be addressed by training in order to improve the efficiency and safety of transfusion therapy. PMID- 26552027 TI - [Differential diagnosis of abdominal cysts in children]. AB - 19 children were diagnosed with abdominal cysts of different origin in the Surgical Unit of the Department of Pediatrics, Medical University of Pecs, Hungary between 2010 and 2013. The authors discuss the details of representative cases of a parovarial cyst, an intestinal duplication, and an omental cyst with emphasis on the clinical symptoms, diagnostic tools, and surgical interventions. The authors conclude that abdominal cysts often cause mild symptoms only, and they are discovered accidentally by ultrasound imaging performed for other reasons. In some cases, the cyst can cause severe complaints or even acute abdomen requiring emergency surgery. Laporoscopy may be a valuable method both in diagnosis and surgical therapy. Abdominal CT or MRI are not required in the majority of the patients. PMID- 26552028 TI - [Multiple sclerosis with stroke-like symptoms: a diagnostic challenge. Case report]. AB - Stroke-like presentation of multiple sclerosis is a challenging diagnosis requiring quick and efficient decision in order to provide the best possible therapeutical option. This case presentation focuses on the difficulties of the differential diagnostic process. Even if signs were misleading, the stepwise and structured approach with the use of adequate diagnostic tools revealed the most likely diagnosis and, thus, assured the best clinical care. PMID- 26552030 TI - Differentiation of Wines Treated with Wood Chips Based on Their Phenolic Content, Volatile Composition, and Sensory Parameters. AB - The effects of both wood chips addition and contact time on phenolic content, volatile composition, color parameters, and organoleptic character of red wine made by a native Greek variety (Agiorgitiko) were evaluated. For this purpose, chips from American, French, Slavonia oak, and Acacia were added in the wine after fermentation. A mixture consisting of 50% French and 50% Americal oak chips was also evaluated. In an attempt to categorize wine samples, various chemical parameters of wines and sensory parameters were studied after 1, 2, and 3 mo of contact time with chips. The results showed that regardless of the type of wood chips added in the wines, it was possible to differentiate the samples according to the contact time based on their phenolic composition and color parameters. In addition, wood-extracted volatile compounds seem to be the critical parameter that could separate the samples according to the wood type. The wines that were in contact with Acacia and Slavonia chips could be separated from the rest mainly due to their distinct sensory characters. PMID- 26552031 TI - Photochromic Properties of Tungsten Oxide/Methylcellulose Composite Film Containing Dispersing Agents. AB - Tungsten oxide-based photochromic films which changed reversibly in air between colorless- transparent in the dark and dark blue under UV irradiation were prepared by using methylcellulose as a film matrix and polyols such as ethylene glycol (EG), propylene glycol (PG), and glycerin (Gly) as dispersing agents. Influence of the dispersing agents and water in the films on the photochromic behavior was systematically studied. Under UV irradiation, absorption bands around 640 and 980 nm increased and the coloring rate was the following order: Gly > EG > PG. An increase in the amounts of dispersing agents or water accelerated the coloring rate. By increasing the water content of the film, a new absorption peak appeared at ca. 775 nm and the Raman spectra indicated a shift of W-O-W stretching vibration to lower wavenumber which was due to the formation of hydrogen bonding. All absorption spectra were fit by three Lorentz functions, whose bands were ascribed to various packing of WO6 octahedra. After the light was turned off, the formation of W(5+) was stopped and bleaching occurred by the reaction with O2 in air to recover its original transparent state. We anticipate that the biodegradable photochromic films developed in this study can be applied in recyclable display medium and especially in detachable films for glass windows whose light transmission properties are changed by sunlight, i.e., for usage as an alternative of smart windows without applying voltage. PMID- 26552032 TI - Stochastic Leader Gravitational Search Algorithm for Enhanced Adaptive Beamforming Technique. AB - In this paper, stochastic leader gravitational search algorithm (SL-GSA) based on randomized k is proposed. Standard GSA (SGSA) utilizes the best agents without any randomization, thus it is more prone to converge at suboptimal results. Initially, the new approach randomly choses k agents from the set of all agents to improve the global search ability. Gradually, the set of agents is reduced by eliminating the agents with the poorest performances to allow rapid convergence. The performance of the SL-GSA was analyzed for six well-known benchmark functions, and the results are compared with SGSA and some of its variants. Furthermore, the SL-GSA is applied to minimum variance distortionless response (MVDR) beamforming technique to ensure compatibility with real world optimization problems. The proposed algorithm demonstrates superior convergence rate and quality of solution for both real world problems and benchmark functions compared to original algorithm and other recent variants of SGSA. PMID- 26552033 TI - Loss of Consciousness at Onset of Subarachnoid Hemorrhage as an Important Marker of Early Brain Injury. AB - IMPORTANCE: Loss of consciousness (LOC) is a common presenting symptom of subarachnoid hemorrhage (SAH) that is presumed to result from transient intracranial circulatory arrest. OBJECTIVE: To clarify the association between LOC at onset of SAH, complications while in the hospital, and long-term outcome after SAH. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was conducted of 1460 consecutively treated patients with spontaneous SAH who were part of a prospective observational cohort study at a large urban academic medical center (the Columbia University SAH Outcomes Project or SHOP). Patients were enrolled between August 6, 1996, and July 23, 2012. Analysis was conducted from December 1, 2013, to February 28, 2015. EXPOSURES: Loss of consciousness at onset was identified by structured interview of the patient and first responders. Patients (80.5%) were observed for up to 1 year to assess functional recovery. MAIN OUTCOMES AND MEASURES: Modified Rankin scale scores were assigned based on telephone or in-person interviews of the patient, family members, or caregivers. Complications while in the hospital were predefined and adjudicated by the study team. RESULTS: Five hundred ninety patients (40.4%) reported LOC at onset of SAH. Loss of consciousness was associated with poor clinical grade, more subarachnoid and intraventricular blood seen on admission computed tomographic scan, and a higher frequency of global cerebral edema (P < .001). Loss of consciousness was also associated with more prehospital tonic-clonic activity (22.7% vs 4.2%; P < .001) and cardiopulmonary arrest (9.7% vs 0.5%, P < .001) vs patients who did not experience LOC. In multivariable analysis, death or severe disability at 12 months was independently associated with LOC after adjusting for established risk factors for poor outcome, including poor admission clinical grade (adjusted odds ratio, 1.94; 95% CI, 1.38-2.72; P < .001). There was no association between LOC at onset and delayed cerebral ischemia or aneurysm rebleeding. CONCLUSIONS AND RELEVANCE: Loss of consciousness at symptom onset is an important manifestation of early brain injury after SAH and a predictor of death or poor functional outcome at 12 months. PMID- 26552034 TI - Anterior petrosal approach: The safety of Kawase triangle as an anatomical landmark for anterior petrosectomy in petroclival meningiomas. AB - OBJECT: Anterior petrosectomy through the middle fossa is a well-described option for addressing cranial base lesions of the petroclival region. To access posterior fossa through middle fossa, we quantitatively evaluate the safety of Kawase triangle as an anatomical landmark. METHOD: We reviewed pre- and postoperative Multi-Slice CT scan (1mm thickness) of patients with petroclival meningioma between Jan 2009 and Sep 2013 in which anterior petrosectomy was performed to access the posterior fossa part of the tumor. The distances between drilling start and finish edge to the vital anatomical skull base structures such as internal auditory canal (IAC) and superior semicircular canal and petrous apex (petrous part of the carotid artery) were measured and analyzed. RESULTS: Drilling entrance length is directly related with tumor size. The distances between anatomical structures and drilling points decrease with increasing tumor size, but it always remains a safe margin between drilling points and IAC, internal carotid artery (ICA), and semicircular canals in axial and coronal views. CONCLUSION: The Kawase triangle is shown to be a safe anatomical landmark for anterior petrosectomy. The described landmarks avoid damage to the vital anatomical structures during access to the posterior fossa through middle fossa, despite temporal bone anatomical variations and different tumor sizes. PMID- 26552037 TI - B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation. AB - Alloreactive memory T cells mediate accelerated allograft rejection and transplant tolerance resistance. Recent studies have shown that B cell deficient MUMT mice fail to mount donor-specific memory T cell responses after transplantation. At the same time, other studies showed that pretransplant B cell depletion using rituximab (IgG1 anti-CD20 mAb) combined with cyclosporine A promoted the survival of islet allografts in monkeys. In this study, we investigated the effect of anti-CD20 antibody-mediated B cell depletion on the memory T cell alloresponse in mice. Wild-type and anti-OVA TCR transgenic mice were treated with an IgG2a anti-CD20 monoclonal antibody, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs but spared some B cells in the bone marrow. B cell depletion did not affect the direct alloresponse but resulted in a marked increase of indirect alloresponse after skin transplantation of naive mice. Furthermore, in allosensitized mice, anti CD20 mAb treatment enhanced the reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti-CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered. PMID- 26552038 TI - Behavioral and neurobiological correlates of childhood apraxia of speech in Italian children. AB - Childhood apraxia of speech (CAS) is a neurogenic Speech Sound Disorder whose etiology and neurobiological correlates are still unclear. In the present study, 32 Italian children with idiopathic CAS underwent a comprehensive speech and language, genetic and neuroradiological investigation aimed to gather information on the possible behavioral and neurobiological markers of the disorder. The results revealed four main aggregations of behavioral symptoms that indicate a multi-deficit disorder involving both motor-speech and language competence. Six children presented with chromosomal alterations. The familial aggregation rate for speech and language difficulties and the male to female ratio were both very high in the whole sample, supporting the hypothesis that genetic factors make substantial contribution to the risk of CAS. As expected in accordance with the diagnosis of idiopathic CAS, conventional MRI did not reveal macrostructural pathogenic neuroanatomical abnormalities, suggesting that CAS may be due to brain microstructural alterations. PMID- 26552039 TI - Effect of the Combination of Ezetimibe and Simvastatin on Gluconeogenesis and Oxygen Consumption in the Rat Liver. AB - The aim of this work was to investigate the effects of chronic treatment with the combination of ezetimibe and simvastatin on gluconeogenesis in rat liver. Rats were treated daily for 28 days with the combination of ezetimibe and simvastatin (10/40 mg/kg) by oral gavage. To measure gluconeogenesis and the associated pathways, isolated perfused rat liver was used. In addition, subcellular fractions, such as microsomes and mitochondria, were used for complementary measures of enzymatic activities. Treatment with the combination of simvastatin and ezetimibe resulted in a decrease in gluconeogenesis from pyruvate (-62%). Basal oxygen consumption of the treated animals was higher (+22%) than that of the control rats, but the resulting oxygen consumption that occurred after pyruvate infusion was 43% lower in animals treated with the combination of simvastatin and ezetimibe. Oxygen consumption in the livers from treated animals was completely inhibited by cyanide (electron transport chain inhibitor), but not by proadifen (cytochrome P450 inhibitor). Chronic treatment with ezetimibe/simvastatin decreased the activity of the key enzymes glucose-6 phosphatase and fructose-1,6-bisphosphatase by 59% and 45%, respectively, which is probably the major reason for the decreased gluconeogenesis seen in ezetimibe /simvastatin-treated rats. It is also possible that part of the effect of this combination on gluconeogenesis and on the oxygen consumption is related to the impairment of mitochondrial energy transduction. PMID- 26552040 TI - Effects of bariatric weight loss surgery on glucose metabolism, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese adults. AB - BACKGROUND: We determined effects of bariatric weight loss surgery on serum tartrate-resistant acid phosphatase 5a (TRACP 5a), inflammatory cytokines and glucose homeostasis in severely obese Chinese adults. METHODS: Severely obese adults undergoing bariatric surgery were recruited. Anthropometry, insulin resistance (IR), inflammatory markers and serum TRACP 5a were measured at baseline and 3, 6 and 12months postoperatively. RESULTS: Data of 93 patients, including 69 non-diabetic (non-DM group) and 24 diabetic (DM group), were analyzed. Anthropometry decreased significantly at 3months postoperatively in both groups; low-density lipoprotein cholesterol decreased obviously at 3, 6 and 12months in non-DM group, while improving significantly at 6 and 12months in DM group. Homeostasis model assessment for IR (HOMA-IR) improved significantly at 3, 6 and 12months in non-DM group and 12months in DM group. In DM group, C-reactive protein (CRP) decreased significantly at 3months postoperatively and inflammatory markers interleukin-6 (IL-6) and TRACP 5a improved at 6months postoperatively; in non-DM group, serum TRACP 5a decreased obviously at 12months postoperatively without significant changes in CRP and IL-6. CONCLUSION: Weight reduction by bariatric surgery decreases anthropometry, IR, lipids and inflammatory markers in severely obese Chinese adults. PMID- 26552041 TI - White-Light-Induced Collective Heating of Gold Nanocomposite/Bombyx mori Silk Thin Films with Ultrahigh Broadband Absorbance. AB - This paper describes a systematic investigation of the phenomenon of white-light induced heating in silk fibroin films embedded with gold nanoparticles (Au NPs). The Au NPs functioned to develop an ultrahigh broadband absorber, allowing white light to be used as a source for photothermal generation. With an increase of the Au content in the composite films, the absorbance was enhanced significantly around the localized surface plasmon resonance (LSPR) wavelength, while non-LSPR wavelengths were also increased dramatically. The greater amount of absorbed light increased the rate of photoheating. The optimized composite film exhibited ultrahigh absorbances of approximately 95% over the spectral range from 350 to 750 nm, with moderate absorbances (>60%) at longer wavelengths (750-1000 nm). As a result, the composite film absorbed almost all of the incident light and, accordingly, converted this optical energy to local heat. Therefore, significant temperature increases (ca. 100 degrees C) were readily obtained when we irradiated the composite film under a light-emitting diode or halogen lamp. Moreover, such composite films displayed linear light-to-heat responses with respect to the light intensity, as well as great photothermal stability. A broadband absorptive film coated on a simple Al/Si Schottky diode displayed a linear, significant, stable photo-thermo-electronic effect in response to varying the light intensity. PMID- 26552042 TI - Clinical and Anatomical Follow-up in Patients With Aneurysms Treated With the WEB Device: 1-Year Follow-up Report in the Cumulated Population of 2 Prospective, Multicenter Series (WEBCAST and French Observatory). AB - BACKGROUND: Flow disruption with WEB is an innovative endovascular approach for wide-neck bifurcation aneurysms. Initial series have shown a low complication rate with good efficacy. OBJECTIVE: To report clinical and anatomical results of the WEB treatment in the cumulated population of WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm) and French Observatory series. METHODS: WEBCAST and French Observatory are single-arm, prospective, multicenter, Good Clinical Practice studies dedicated to the evaluation of WEB treatment. Ruptured and unruptured bifurcation aneurysms located in the basilar artery, middle cerebral artery, anterior communicating artery, and internal carotid artery terminus were included in both studies. Clinical data were independently evaluated. Postoperative, 6-month (in WEBCAST), and 1-year aneurysm occlusion was independently evaluated with a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The cumulated population was 113 patients (74 female, 65.5%) 33 to 74 years of age with 114 aneurysms with a mean neck size of 5.6 mm. There was no mortality at 1 month, and morbidity was 2.7%. A statistically significant difference in the rate of occurrence of thromboembolic events was observed between the use of any antiplatelet agent and the use of no antiplatelet agent (P < .001). At 1 year, complete aneurysm occlusion was observed in 56.0%, neck remnant in 26.0%, and aneurysm remnant in 18.0%. Worsening of aneurysm occlusion between the procedure and 12 months was observed in 2.0% and between 6 months and 1 year in 7.1%. CONCLUSION: The analysis in this large cumulated population of studies confirms favorable safety and efficacy of WEB treatment. PMID- 26552043 TI - Commentary: Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery: A Histology-Based Evaluation. PMID- 26552044 TI - Does a More Centrally Located School Promote Walking to School? Spatial Centrality in School-Neighborhood Settings. AB - BACKGROUND: A public elementary school has traditionally functioned as an important center of a neighborhood, but this role has diminished with sprawling urban developments. Despite the large number of studies of children's walking to/from school (WTS), the school's location in relation to the larger neighborhood context has not been fully explored. This study is to examine the relationship between school's spatial centrality and children's WTS in urban, suburban and rural settings. METHODS: this study used school travel tally (11,721 students), environment audit, GIS and census data from 71 elementary school/neighborhoods in Texas, and employed the closeness centrality index to estimate a school's spatial centrality. Data were collected from 2009-2012. RESULTS: After controlling for neighborhood characteristics, it was found that more centrally located schools are likely to have higher proportions of WTS in the neighborhoods. And, among urban, suburban and rural settings, urban schools were the most and rural schools were the least likely to be centrally-located in the neighborhoods. CONCLUSIONS: The findings offer implications on school and community planning policies that can help promote WTS. Spatial centrality measures can be effective tools to identify environmental factors in complex urban networks related to human behaviors and community-based activities. PMID- 26552045 TI - Low PAPP-A: the impact of ultrasound to evaluate fetal growth. AB - OBJECTIVE: Our objective was to describe utilization and impact of sonographic growth assessment in pregnancies with low pregnancy-associated plasma protein-A (PAPP-A). METHODS: Singleton pregnancies with PAPP-A <=5th percentile and no other risk factors for fetal growth restriction from January 2011-June 2013 were included. Antepartum and delivery data were obtained by reviewing medical records. Outcomes of pregnancies referred for sonographic growth assessment were compared with those not referred for ultrasound. Fisher's exact test, chi-square analysis, and Mann-Whitney U were used for statistical comparison. RESULTS: Two hundred ninety-five patients were included. Of 285 pregnancies reaching the third trimester, 77.5% were referred for ultrasound, with the initial scan at a median gestational age of 28 weeks [26-29]. Referral for growth scans was associated with earlier gestational age at delivery and higher rates of delivery for fetal indications. Those who did not undergo growth scans were more likely to deliver a small for gestational age infant at term, 20.7% versus 35.0% (p = 0.04). There was one third-trimester fetal demise, occurring in a patient who had been undergoing growth scans. CONCLUSION: Growth scans in those with low PAPP-A were associated with delivery at earlier gestational age, with higher rates of delivery for fetal indications and lower rates of small for gestational age newborns at term. No significant differences in neonatal outcomes were observed. PMID- 26552046 TI - Regulation of intestinal SGLT1 by catestatin in hyperleptinemic type 2 diabetic mice. AB - The small intestine is the major site for nutrient absorption that is critical in maintenance of euglycemia. Leptin, a key hormone involved in energy homeostasis, directly affects nutrient transport across the intestinal epithelium. Catestatin (CST), a 21-amino acid peptide derived from proprotein chromogranin A, has been shown to modulate leptin signaling. Therefore, we reasoned that leptin and CST could modulate intestinal Na(+)-glucose transporter 1 (SGLT1) expression in the context of obesity and diabetes. We found that hyperleptinemic db/db mice exhibit increased mucosal mass, associated with an enhanced proliferative response and decreased apoptosis in intestinal crypts, a finding absent in leptin-deficient ob/ob mice. Intestinal SGLT1 abundance was significantly decreased in hyperleptinemic but not leptin-deficient mice, indicating leptin regulation of SGLT1 expression. Phlorizin, a SGLT1/2 inhibitor, was without effect in an oral glucose tolerance test in db/db mice. The alterations in architecture and SGLT1 abundance were not accompanied by changes in the localization of intestinal alkaline phosphatase, indicating intact differentiation. Treatment of db/db mice with CST restored intestinal SGLT1 abundance and intestinal turnover, suggesting a cross-talk between leptin and CST, without affecting plasma leptin levels. Consistent with this hypothesis, we identified structural homology between CST and the AB-loop of leptin and protein-protein docking revealed binding of CST and leptin with the Ig-like binding site-III of the leptin receptor. In summary, downregulation of SGLT1 in an obese type 2 diabetic mouse model with hyperleptinemia is presumably mediated via the short form of the leptin receptor and reduces overt hyperglycemia. PMID- 26552047 TI - Activation of endothelial NAD(P)H oxidase accelerates early glomerular injury in diabetic mice. AB - Increased generation of reactive oxygen species (ROS) is a common denominative pathogenic mechanism underlying vascular and renal complications in diabetes mellitus. Endothelial NAD(P)H oxidase is a major source of vascular ROS, and it has an important role in endothelial dysfunction. We hypothesized that activation of endothelial NAD(P)H oxidase initiates and worsens the progression of diabetic nephropathy, particularly in the development of albuminuria. We used transgenic mice with endothelial-targeted overexpression of the catalytic subunit of NAD(P)H oxidase, Nox2 (NOX2TG). NOX2TG mice were crossed with Akita insulin-dependent diabetic (Akita) mice that develop progressive hyperglycemia. We compared the progression of diabetic nephropathy in Akita versus NOX2TG-Akita mice. NOX2TG Akita mice and Akita mice developed significant albuminuria above the baseline at 6 and 10 weeks of age, respectively. Compared with Akita mice, NOX2TG-Akita mice exhibited higher levels of NAD(P)H oxidase activity in glomeruli, developed glomerular endothelial perturbations, and attenuated expression of glomerular glycocalyx. Moreover, in contrast to Akita mice, the NOX2TG-Akita mice had numerous endothelial microparticles (blebs), as detected by scanning electron microscopy, and increased glomerular permeability. Furthermore, NOX2TG-Akita mice exhibited distinct phenotypic changes in glomerular mesangial cells expressing alpha-smooth muscle actin, and in podocytes expressing increased levels of desmin, whereas the glomeruli generated increased levels of ROS. In conclusion, activation of endothelial NAD(P)H oxidase in the presence of hyperglycemia initiated and exacerbated diabetic nephropathy characterized by the development of albuminuria. Moreover, ROS generated in the endothelium compounded glomerular dysfunctions by altering the phenotypes of mesangial cells and compromising the integrity of the podocytes. PMID- 26552049 TI - Daylight photodynamic therapy with MAL cream for large-scale photodamaged skin based on the concept of 'actinic field damage': recommendations of an international expert group. AB - Conventional PDT (c-PDT) is a widely used and approved non-invasive treatment for actinic keratosis (AK). Recent clinical, histological and immunohistochemical observations have shown that c-PDT with methyl aminolevulinate (MAL) may also partially reverse the signs of photodamage. However, pain and the need for special light source equipment are limiting factors for its use, especially in the treatment of large areas. More recently, daylight PDT (DL-PDT) has been shown to be similar to c-PDT in the treatment of AK, nearly painless and more convenient to perform. To establish consensus on recommendations for the use of MAL DL-PDT in patients with large-scale photodamaged skin. The expert group was comprised of eight dermatologists. Consensus was developed based on the personal experience of the experts in c-PDT and DL-PDT, and results of an extensive literature review. MAL DL-PDT for large areas of photodamaged skin was evaluated and recommendations based on broad clinical experience were provided. As supported by evidence-based data from multicentre studies conducted in Australia and Europe, the authors defined the concept of 'actinic field damage' which refers to photodamage associated with actinic epidermal dysplasia, and provide comprehensive guidelines for the optimal use of DL-PDT in the treatment of actinic field damage. The authors concluded that MAL DL-PDT has a similar efficacy to c-PDT at 3-month (lesion complete response rate of 89% vs. 93% in the Australian study and 70% vs. 74% in the European study (95% C.I. = [-6.8;-0.3] and [-9.5;2.4] respectively) and 6-month follow-ups (97% maintenance of complete lesion response) in the treatment of AKs. The authors agree that DL-PDT is not only efficacious but also nearly pain-free and easy to perform, and therefore results in high patient acceptance especially for the treatment of areas of actinic field damage. PMID- 26552048 TI - Methylation of Cervical Neoplastic Cells Infected With Human Papillomavirus 16. AB - OBJECTIVE: This study was conducted to evaluate the role of methylation of adenylate cyclase activating peptide 1 (ADCYAP1), paired box gene 1 (PAX1), cell adhesion molecule 1 (CADM1), and T-lymphocyte maturation-associated protein (MAL) during carcinogenesis. METHODS: We evaluated the methylation of 4 genes by using the cervical carcinoma cell lines (CaSki, SiHa, HeLa, and C33A) and cervical neoplastic cells from 56 subjects with human papillomavirus 16 (HPV16)-infected low-grade squamous intraepithelial lesions (LSILs), 50 subjects with HPV16 infected high-grade squamous intraepithelial lesions (HSILs), and 24 subjects with HPV16-infected invasive cervical cancer who attended Seoul St. Mary's Hospital. Methylation of the 4 genes was evaluated using quantitative bisulfate pyrosequencing. RESULTS: The ADCYAP1 promoter was hypermethylated in the 4 cell lines (CaSki, 97.40 +/- 1.39; SiHa, 82.04 +/- 17.02; HeLa, 96.14 +/- 2.08; and C33A, 78 +/- 10.18). PAX1 and CADM1 were hypermethylated in the HPV16/18-infected cell lines CaSki (PAX1, 91.18 +/- 9.91; CADM1, 93.5 +/- 7.33), SiHa (PAX1, 96.14 +/- 2.08; CADM1, 93.15 +/- 8.81), and HeLa (PAX1, 82.04 +/- 17.02; CADM1, 92.43 +/- 9.95). MAL was hypermethylated in the CaSki cell line (96.04 +/- 4.74). Among human cervical neoplastic cells, the methylation indices of ADCYAP1 were 7.8 (95% confidence interval [95% CI], 7.0-8.6) in subjects with LSILs and 39.8 (95% CI, 29.0-54.7) in those with cervical cancer (P < 0.001); for PAX1, 7.2 (95% CI, 6.1 8.5) and 37.8 (95% CI, 27.1-52.7), respectively; for CADM1, 3.5 (95% CI, 3.0-4.0) and 17.7 (95% CI, 10.8-29.1), respectively; for MAL, 2.7 (95% CI, 2.5-3.0) and 13.0 (95% CI, 7.6-22.0), respectively (P < 0.001 for each). Immunohistochemical staining results were positive in the cytoplasm of subjects with low methylation of the 4 gene promoters; however, they were negative in the cytoplasm of those with hypermethylation of the 4 gene promoters. CONCLUSIONS: The results of this study suggest that the methylation of ADCYAP1, PAX1, CADM1, and MAL may be highly associated with the development of cervical cancer, and that gene expression can be suppressed by gene promoter hypermethylation. PMID- 26552050 TI - Simple technique for high-throughput marking of distinguishable micro-areas for microscopy. AB - Today's (nano)-functional materials, usually exhibiting complex physical properties require local investigation with different microscopy techniques covering different physical aspects such as dipolar and magnetic structure. However, often these must be employed on the very same sample position to be able to truly correlate those different information and corresponding properties. This can be very challenging if not impossible especially when samples lack prominent features for orientation. Here, we present a simple but effective method to mark hundreds of approximately 15*15 MUm sample areas at one time by using a commercial transmission electron microscopy grid as shadow mask in combination with thin-film deposition. Areas can be easily distinguished when using a reference or finder grid structure as shadow mask. We show that the method is suitable to combine many techniques such as light microscopy, scanning probe microscopy and scanning electron microscopy. Furthermore, we find that best results are achieved when depositing aluminium on a flat sample surface using electron-beam evaporation which ensures good line-of-sight deposition. This inexpensive high-throughput method has several advantageous over other marking techniques such as focused ion-beam processing especially when batch processing or marking of many areas is required. Nevertheless, the technique could be particularly valuable, when used in junction with, for example focused ion-beam sectioning to obtain a thin lamellar of a particular pre-selected area. PMID- 26552051 TI - Comparison of the Impact of Zinc Vacancies on Charge Separation and Charge Transfer at ZnO/Sexithienyl and ZnO/Fullerene Interfaces. AB - The impact of surface zinc vacancies on charge transfer and charge separation at donor/ZnO and acceptor/ZnO interfaces is identified via density functional theory calculations. The results show their effect to be related to the stronger internal electric field present near these vacancies. Thus, such surface defects can have a significant negative impact on the performance of hybrid solar cells using ZnO as electron acceptors. PMID- 26552052 TI - Highly selective category-specific deficits of visual processing at a stage of access to the semantic representation. PMID- 26552053 TI - Orange web space in a patient with pulmonary tuberculosis. PMID- 26552055 TI - A Novel Pd-Catalysed Annulation Reaction for the Syntheses of Pyrroloindoles and Pyrroloquinolines. AB - Pd-catalysed annulation reactions between indole derivatives and internal alkyne esters leading to various pyrrolo[1,2-a]indoles and pyrroloquinolines have been developed. The strategy involves an intermolecular addition of the indole nitrogen on to the internal alkyne ester followed by an intramolecular insertion of a vinyl-palladium complex into the carbonyl group. This method offers a facile and practical approach to pyrrolo[1,2-a]indoles and pyrroloquinolines. PMID- 26552056 TI - Recent progress towards all-renewable electricity supplies. PMID- 26552057 TI - Activating and optimizing MoS2 basal planes for hydrogen evolution through the formation of strained sulphur vacancies. AB - As a promising non-precious catalyst for the hydrogen evolution reaction (HER; refs ,,,,), molybdenum disulphide (MoS2) is known to contain active edge sites and an inert basal plane. Activating the MoS2 basal plane could further enhance its HER activity but is not often a strategy for doing so. Herein, we report the first activation and optimization of the basal plane of monolayer 2H-MoS2 for HER by introducing sulphur (S) vacancies and strain. Our theoretical and experimental results show that the S-vacancies are new catalytic sites in the basal plane, where gap states around the Fermi level allow hydrogen to bind directly to exposed Mo atoms. The hydrogen adsorption free energy (DeltaGH) can be further manipulated by straining the surface with S-vacancies, which fine-tunes the catalytic activity. Proper combinations of S-vacancy and strain yield the optimal DeltaGH = 0 eV, which allows us to achieve the highest intrinsic HER activity among molybdenum-sulphide-based catalysts. PMID- 26552058 TI - Tough bonding of hydrogels to diverse non-porous surfaces. AB - In many animals, the bonding of tendon and cartilage to bone is extremely tough (for example, interfacial toughness ~800 J m(-2); refs ,), yet such tough interfaces have not been achieved between synthetic hydrogels and non-porous surfaces of engineered solids. Here, we report a strategy to design tough transparent and conductive bonding of synthetic hydrogels containing 90% water to non-porous surfaces of diverse solids, including glass, silicon, ceramics, titanium and aluminium. The design strategy is to anchor the long-chain polymer networks of tough hydrogels covalently to non-porous solid surfaces, which can be achieved by the silanation of such surfaces. Compared with physical interactions, the chemical anchorage results in a higher intrinsic work of adhesion and in significant energy dissipation of bulk hydrogel during detachment, which lead to interfacial toughness values over 1,000 J m(-2). We also demonstrate applications of robust hydrogel-solid hybrids, including hydrogel superglues, mechanically protective hydrogel coatings, hydrogel joints for robotic structures and robust hydrogel-metal conductors. PMID- 26552059 TI - Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity. AB - Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL 1beta and IFN-gamma expression by regulating PI3K/Akt/mTOR signaling and NF kappaB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-beta expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries. PMID- 26552060 TI - Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation. AB - Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided. PMID- 26552062 TI - Evidence of a Link Between Grip Strength and Type 2 Diabetes Prevalence and Severity Among a National Sample of U.S. Adults. AB - OBJECTIVE: Examine the association between grip strength and type 2 diabetes prevalence and severity. METHODS: Using data from NHANES 2011-2012, objectively determined hand grip strength was assessed using the Takei digital grip strength dynamometer, with diabetes assessed via physician diagnosis and glycohemoglobin A1C. RESULTS: A 5 kg greater grip strength was associated with a 14% lower odds of having diabetes for men (ORadjusted = 0.86; 95% CI: 0.79 to 0.94; P = .002). Similarly, for women, a 5 kg greater grip strength was associated with an 18% lower odds of having diabetes (ORadjusted = 0.82; 95% CI: 0.69 to 0.97; P = .03). Grip strength was also associated with glycohemoglobin A1C among women with diabetes (betaadjusted = -0.26, 95% CI: -0.39 to -0.12; P = .001), which suggests that grip strength is associated with diabetes severity among women. CONCLUSIONS: For both men and women, grip strength is associated with type 2 diabetes presence, and among women, grip strength is associated with severity of type 2 diabetes. PMID- 26552061 TI - BACE-1, PS-1 and sAPPbeta Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies. AB - Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and fibber degeneration, represented by the accumulation of protein depots constituted by beta-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender paired healthy controls were collected and stored at -80 degrees C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-alpha), mitochondrial-related molecules (free plasmatic mitochondrial DNA [mtDNA], fibroblast growth factor-21 [FGF-21] and coenzyme-Q10 [CoQ]) and amyloidogenic-related molecules (beta-secretase-1 [BACE-1], presenilin-1 [PS-1], and soluble Abeta precursor protein [sAPPbeta]) were assessed with magnetic bead based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-alpha, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE 1, PS-1 and sAPPbeta levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies (p < 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE 1, PS-1 and sAPPbeta represent a good predictive noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis. PMID- 26552054 TI - Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. AB - IMPORTANCE: Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity. OBJECTIVE: To examine the association between supplemental probiotic use during the first year of life and islet autoimmunity among children at increased genetic risk of T1DM. DESIGN, SETTING, AND PARTICIPANTS: In this ongoing prospective cohort study that started September 1, 2004, children from 6 clinical centers, 3 in the United States (Colorado, Georgia/Florida, and Washington) and 3 in Europe (Finland, Germany, and Sweden), were followed up for T1DM-related autoantibodies. Blood samples were collected every 3 months between 3 and 48 months of age and every 6 months thereafter to determine persistent islet autoimmunity. Details of infant feeding, including probiotic supplementation and infant formula use, were monitored from birth using questionnaires and diaries. We applied time-to-event analysis to study the association between probiotic use and islet autoimmunity, stratifying by country and adjusting for family history of type 1 diabetes, HLA-DR-DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child's antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking. Altogether 8676 infants with an eligible genotype were enrolled in the follow-up study before the age of 4 months. The final sample consisted of 7473 children with the age range of 4 to 10 years (as of October 31, 2014). EXPOSURES: Early intake of probiotics. MAIN OUTCOMES AND MEASURES: Islet autoimmunity revealed by specific islet autoantibodies. RESULTS: Early probiotic supplementation (at the age of 0-27 days) was associated with a decreased risk of islet autoimmunity when compared with probiotic supplementation after 27 days or no probiotic supplementation (hazard ratio [HR], 0.66; 95% CI, 0.46-0.94). The association was accounted for by children with the DR3/4 genotype (HR, 0.40; 95% CI, 0.21-0.74) and was absent among other genotypes (HR, 0.97; 95% CI, 0.62 1.54). CONCLUSIONS AND RELEVANCE: Early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of T1DM. The result needs to be confirmed in further studies before any recommendation of probiotics use is made. PMID- 26552063 TI - Longitudinal Study on the Association Between Cardiorespiratory Fitness, Anthropometric Parameters and Blood Lipids. AB - BACKGROUND: Longitudinal evidence concerning the association between cardiorespiratory fitness (CRF) and blood lipids and between anthropometric parameters (ANTP) and blood lipids is limited. This study aimed to investigate the association between changes in CRF and ANTP and changes in blood lipids. METHODS: In 2002-2004 and 2012-2014, 652 participants were tested. CRF was measured as VO2peak using a maximal ergometer test. Waist circumference (WC) and Body Mass Index (BMI) were used as ANTP. Blood samples were analyzed for total cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides. A linear regression analysis was performed to investigate associations between changes in CRF and ANTP and changes in blood lipids. RESULTS: After adjustment a decrease in CRF was associated with an increase in triglycerides and a decrease in HDL cholesterol in men. An increase in WC was associated with an increase in TC, LDL cholesterol and ratio total/HDL cholesterol and a decrease in HDL cholesterol, while an increase in BMI was associated with an increase in ratio total/HDL cholesterol and a decrease in HDL cholesterol. CONCLUSIONS: WC and BMI were more longitudinally associated with blood lipids compared with CRF. Improving ANTP can enhance the blood lipid profile, while CRF had only limited influence. PMID- 26552065 TI - Use of Social Networking Sites and Adherence to Physical Activity and Screen Time Recommendations in Adolescents. AB - BACKGROUND: Adolescents are recommended to achieve >= 60 min/day of moderate-to vigorous physical activity (PA) and <=2 h/day of screen time (ST). This study examined the relationships between the use of social networking sites (SNSs) and adherence to PA and ST recommendations in a large sample of Canadian adolescents. METHODS: This cross-sectional school-based survey included a representative sample of 9388 students in grades 7 to 12 across Ontario, Canada. RESULTS: After adjustment for several confounding variables, results showed that male adolescents who use SNSs for fewer hours (<= 1 h/day) had greater odds of adherence to PA and to both PA and ST recommendations concurrently, while those who use it for more hours (>= 3 h/day) had lower odds of adherence to the ST recommendation. Female adolescents who use SNSs for more hours had lower odds of adherence to the ST recommendation (use of SNSs >= 2 h/day) and to both PA and ST recommendations concurrently (use of SNSs >= 5 h/day). CONCLUSIONS: Heavy use of SNSs has a negative influence on the adherence to the ST recommendation in both males and females; however, infrequent use of SNSs was related to the adherence to the PA recommendation and concurrent adherence to both recommendations in males only. PMID- 26552064 TI - Change in Physical Activity and Sedentary Time Associated With 2-Year Weight Loss in Obese Adults With Osteoarthritis. AB - BACKGROUND: We examined if changes in moderate-to-vigorous physical activity (MVPA), light activity, and sedentary behavior are related to weight change over a 2-year period in obese adults with/elevated risk for knee osteoarthritis. METHODS: Weight, physical activity, and sedentary time at baseline and 2 years were obtained from 459 obese participants from the Osteoarthritis Initiative. Weight change was categorized as >= 10 lbs, 5.0 to 9.9 lbs, 4.9 to -4.9 lbs, -5.0 to -9.9 lbs, and <= -10 lbs. We examined the association between 2-year weight change categories and changes in activity/sedentary time from accelerometer monitoring by multiple linear regression adjusted for baseline weight, demographic, and health factors. RESULTS: Across the 5 weight categories (loss to gain), average 2-year change ranged from -7.4 to 28.0 sedentary minutes/ day, 4.2 to -23.1 light activity minutes/day, and 3.2 to -4.9 MVPA minutes/day, respectively. Higher weight loss categories were separately associated with increased MVPA (P for trend < 0.001) and less sedentary gain (P for trend = 0.01). Weight loss categories had a strong trend with light activity gain but not statistically significant (P for trend = 0.06). CONCLUSIONS: Small increases in MVPA and decreases in sedentary time over 2 years were associated with weight loss among adults with obesity and with or at elevated risk for knee osteoarthritis. PMID- 26552066 TI - Recent data concerning heparanase: focus on fibrosis, inflammation and cancer. AB - Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-beta. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer. PMID- 26552067 TI - Glyoxalase biochemistry. AB - The glyoxalase enzyme system utilizes intracellular thiols such as glutathione to convert alpha-ketoaldehydes, such as methylglyoxal, into D-hydroxyacids. This overview discusses several main aspects of the glyoxalase system and its likely function in the cell. The control of methylglyoxal levels in the cell is an important biochemical imperative and high levels have been associated with major medical symptoms that relate to this metabolite's capability to covalently modify proteins, lipids and nucleic acid. PMID- 26552068 TI - Efficacy of subgingivally delivered atorvastatin and simvastatin as an adjunct to scaling and root planing. AB - BACKGROUND: The current understanding of the pathogenesis of periodontal disease has resulted in adjunctive use of various pharmacologic agents in periodontal therapy. The objective of this investigation was to assess the efficacy of atorvastatin and simvastatin (because of their pleiotropic properties) as an adjunct to dental scaling and root planing (SRP) by local delivery, i.e. placing them subgingivally, in the treatment of chronic periodontitis. METHODS: Local delivery systems for atorvastatin and simvastatin were prepared in sodium alginate suspension to be administered with calcium chloride solution. Patients diagnosed with chronic periodontitis were grouped as group 1, receiving SRP only (control), group 2, receiving SRP with subgingival delivery of 1.2% simvastatin, and group 3, receiving SRP with subgingival delivery of 1.2% atorvastatin. Clinical parameters and interleukin (IL) 1alpha levels in the gingival crevicular fluid (GCF) were assessed. RESULTS: All three groups showed significant reductions in clinical parameters and IL-1alpha levels in the GCF (p<0.05). However, the test groups did not show any statistically significant difference when compared with control. CONCLUSIONS: Subgingivally delivered atorvastatin and simvastatin as an adjunct to SRP is efficacious but did not demonstrate any added benefit as compared with SRP alone. PMID- 26552069 TI - Scalable High-Performance Image Registration Framework by Unsupervised Deep Feature Representations Learning. AB - Feature selection is a critical step in deformable image registration. In particular, selecting the most discriminative features that accurately and concisely describe complex morphological patterns in image patches improves correspondence detection, which in turn improves image registration accuracy. Furthermore, since more and more imaging modalities are being invented to better identify morphological changes in medical imaging data, the development of deformable image registration method that scales well to new image modalities or new image applications with little to no human intervention would have a significant impact on the medical image analysis community. To address these concerns, a learning-based image registration framework is proposed that uses deep learning to discover compact and highly discriminative features upon observed imaging data. Specifically, the proposed feature selection method uses a convolutional stacked autoencoder to identify intrinsic deep feature representations in image patches. Since deep learning is an unsupervised learning method, no ground truth label knowledge is required. This makes the proposed feature selection method more flexible to new imaging modalities since feature representations can be directly learned from the observed imaging data in a very short amount of time. Using the LONI and ADNI imaging datasets, image registration performance was compared to two existing state-of-the-art deformable image registration methods that use handcrafted features. To demonstrate the scalability of the proposed image registration framework, image registration experiments were conducted on 7.0-T brain MR images. In all experiments, the results showed that the new image registration framework consistently demonstrated more accurate registration results when compared to state of the art. PMID- 26552070 TI - Thermal Dynamics in Newborn and Juvenile Models Cooled by Total Liquid Ventilation. AB - BACKGROUND: Total liquid ventilation (TLV) consists in filling the lungs with a perfluorocarbon (PFC) and using a liquid ventilator to ensure a tidal volume of oxygenated, CO 2 -free and temperature-controlled PFC. Having a much higher thermal capacity than air, liquid PFCs assume that the filled lungs become an efficient heat exchanger with pulmonary circulation. OBJECTIVE: The objective of the present study was the development and validation of a parametric lumped thermal model of a subject in TLV. METHODS: The lungs were modeled as one compartment in which the control volume varied as a function of the tidal volume. The heat transfer in the body was modeled as seven parallel compartments representing organs and tissues. The thermal model of the lungs and body was validated with two groups of lambs of different ages and weights (newborn and juvenile) undergoing an ultrafast mild therapeutic hypothermia induction by TLV. RESULTS: The model error on all animals yielded a small mean error of -0.1 +/-0.4 ( degrees )C for the femoral artery and 0.0 +/-0.1 ( degrees )C for the pulmonary artery. CONCLUSION: The resulting experimental validation attests that the model provided an accurate estimation of the systemic arterial temperature and the venous return temperature. SIGNIFICANCE: This comprehensive thermal model of the lungs and body has the advantage of closely modeling the rapid thermal dynamics in TLV. The model can explain how the time to achieve mild hypothermia between newborn and juvenile lambs remained similar despite of highly different physiological and ventilatory parameters. The strength of the model is its strong relationship with the physiological parameters of the subjects, which suggests its suitability for projection to humans. PMID- 26552071 TI - Toward Standardized Acoustic Radiation Force (ARF)-Based Ultrasound Elasticity Measurements With Robotic Force Control. AB - OBJECTIVE: Acoustic radiation force (ARF)-based approaches to measure tissue elasticity require transmission of a focused high-energy acoustic pulse from a stationary ultrasound probe and ultrasound-based tracking of the resulting tissue displacements to obtain stiffness images or shear wave speed estimates. The method has established benefits in biomedical applications such as tumor detection and tissue fibrosis staging. One limitation, however, is the dependence on applied probe pressure, which is difficult to control manually and prohibits standardization of quantitative measurements. To overcome this limitation, we built a robot prototype that controls probe contact forces for shear wave speed quantification. METHODS: The robot was evaluated with controlled force increments applied to a tissue-mimicking phantom and in vivo abdominal tissue from three human volunteers. RESULTS: The root-mean-square error between the desired and measured forces was 0.07 N in the phantom and higher for the fatty layer of in vivo abdominal tissue. The mean shear wave speeds increased from 3.7 to 4.5 m/s in the phantom and 1.0 to 3.0 m/s in the in vivo fat for compressive forces ranging from 2.5 to 30 N. The standard deviation of shear wave speeds obtained with the robotic approach were low in most cases ( 0.2 m/s) and comparable to that obtained with a semiquantitative landmark-based method. CONCLUSION: Results are promising for the introduction of robotic systems to control the applied probe pressure for ARF-based measurements of tissue elasticity. SIGNIFICANCE: This approach has potential benefits in longitudinal studies of disease progression, comparative studies between patients, and large-scale multidimensional elasticity imaging. PMID- 26552072 TI - Robust PBPK/PD-Based Model Predictive Control of Blood Glucose. AB - GOAL: Automated glucose control (AGC) has not yet reached the point where it can be applied clinically [3]. Challenges are accuracy of subcutaneous (SC) glucose sensors, physiological lag times, and both inter- and intraindividual variability. To address above issues, we developed a novel scheme for MPC that can be applied to AGC. RESULTS: An individualizable generic whole-body physiology based pharmacokinetic and dynamics (PBPK/PD) model of the glucose, insulin, and glucagon metabolism has been used as the predictive kernel. The high level of mechanistic detail represented by the model takes full advantage of the potential of MPC and may make long-term prediction possible as it captures at least some relevant sources of variability [4]. Robustness against uncertainties was increased by a control cascade relying on proportional-integrative derivative based offset control. The performance of this AGC scheme was evaluated in silico and retrospectively using data from clinical trials. This analysis revealed that our approach handles sensor noise with a MARD of 10%-14%, and model uncertainties and disturbances. CONCLUSION: The results suggest that PBPK/PD models are well suited for MPC in a glucose control setting, and that their predictive power in combination with the integrated database-driven (a priori individualizable) model framework will help overcome current challenges in the development of AGC systems. SIGNIFICANCE: This study provides a new, generic, and robust mechanistic approach to AGC using a PBPK platform with extensive a priori (database) knowledge for individualization. PMID- 26552073 TI - Gait Characteristics When Walking on Different Slippery Walkways. AB - OBJECTIVE: This study sought to determine the changes in muscle activity about the ankle, knee, and hip in able-bodied people walking at steady state on surfaces with different degrees of slipperiness. METHODS: Muscle activity was measured through electromyographic signals from selected lower limb muscles and quantified to directly compare changes across surface conditions. RESULTS: Our results showed distinct changes in the patterns of muscle activity controlling each joint. Muscles controlling the ankle showed a significant reduction in activity as the surface became more slippery, presumably resulting in a compliant distal joint to facilitate full contact with the surface. Select muscles about the knee and hip showed a significant increase in activity as the surface became more slippery. This resulted in increased knee and hip flexion likely contributing to a lowering of the body's center of mass and stabilization of the proximal leg and trunk. CONCLUSION: These findings suggest a proximal-distal gradient in the control of muscle activity that could inform the future design of adaptable prosthetic controllers. SIGNIFICANCE: Walking on a slippery surface is extremely difficult, especially for individuals with lower limb amputations because current prostheses do not allow the compensatory changes in lower limb dynamics that occur involuntarily in unimpaired subjects. With recent advances in prosthetic control, there is the potential to provide some of these compensatory changes; however, we first need to understand how able-bodied individuals modulate their gait under these challenging conditions. PMID- 26552074 TI - Local Feature Discriminant Projection. AB - In this paper, we propose a novel subspace learning algorithm called Local Feature Discriminant Projection (LFDP) for supervised dimensionality reduction of local features. LFDP is able to efficiently seek a subspace to improve the discriminability of local features for classification. We make three novel contributions. First, the proposed LFDP is a general supervised subspace learning algorithm which provides an efficient way for dimensionality reduction of large scale local feature descriptors. Second, we introduce the Differential Scatter Discriminant Criterion (DSDC) to the subspace learning of local feature descriptors which avoids the matrix singularity problem. Third, we propose a generalized orthogonalization method to impose on projections, leading to a more compact and less redundant subspace. Extensive experimental validation on three benchmark datasets including UIUC-Sports, Scene-15 and MIT Indoor demonstrates that the proposed LFDP outperforms other dimensionality reduction methods and achieves state-of-the-art performance for image classification. PMID- 26552075 TI - Face Association for Videos Using Conditional Random Fields and Max-Margin Markov Networks. AB - We address the video-based face association problem, in which one attempts to extract the face tracks of multiple subjects while maintaining label consistency. Traditional tracking algorithms have difficulty in handling this task, especially when challenging nuisance factors like motion blur, low resolution or significant camera motions are present. We demonstrate that contextual features, in addition to face appearance itself, play an important role in this case. We propose principled methods to combine multiple features using Conditional Random Fields and Max-Margin Markov networks to infer labels for the detected faces. Different from many existing approaches, our algorithms work in online mode and hence have a wider range of applications. We address issues such as parameter learning, inference and handling false positves/negatives that arise in the proposed approach. Finally, we evaluate our approach on several public databases. PMID- 26552076 TI - Learning And-Or Models to Represent Context and Occlusion for Car Detection and Viewpoint Estimation. AB - This paper presents a method for learning an And-Or model to represent context and occlusion for car detection and viewpoint estimation. The learned And-Or model represents car-to-car context and occlusion configurations at three levels: (i) spatially-aligned cars, (ii) single car under different occlusion configurations, and (iii) a small number of parts. The And-Or model embeds a grammar for representing large structural and appearance variations in a reconfigurable hierarchy. The learning process consists of two stages in a weakly supervised way (i.e., only bounding boxes of single cars are annotated). Firstly, the structure of the And-Or model is learned with three components: (a) mining multi-car contextual patterns based on layouts of annotated single car bounding boxes, (b) mining occlusion configurations between single cars, and (c) learning different combinations of part visibility based on CAD simulations. The And-Or model is organized in a directed and acyclic graph which can be inferred by Dynamic Programming. Secondly, the model parameters (for appearance, deformation and bias) are jointly trained using Weak-Label Structural SVM. In experiments, we test our model on four car detection datasets - the KITTI dataset [1], the PASCAL VOC2007 car dataset [2], and two self-collected car datasets, namely the Street Parking car dataset and the Parking-Lot car dataset, and three datasets for car viewpoint estimation - the PASCAL VOC2006 car dataset [2], the 3D car dataset [3], and the PASCAL3D+ car dataset [4]. Compared with state-of-the-art variants of deformable part-based models and other methods, our model achieves significant improvement consistently on the four detection datasets, and comparable performance on car viewpoint estimation. PMID- 26552077 TI - Robust Correlated and Individual Component Analysis. AB - Recovering correlated and individual components of two, possibly temporally misaligned, sets of data is a fundamental task in disciplines such as image, vision, and behavior computing, with application to problems such as multi-modal fusion (via correlated components), predictive analysis, and clustering (via the individual ones). Here, we study the extraction of correlated and individual components under real-world conditions, namely i) the presence of gross non Gaussian noise and ii) temporally misaligned data. In this light, we propose a method for the Robust Correlated and Individual Component Analysis (RCICA) of two sets of data in the presence of gross, sparse errors. We furthermore extend RCICA in order to handle temporal incongruities arising in the data. To this end, two suitable optimization problems are solved. The generality of the proposed methods is demonstrated by applying them onto 4 applications, namely i) heterogeneous face recognition, ii) multi-modal feature fusion for human behavior analysis (i.e., audio-visual prediction of interest and conflict), iii) face clustering, and iv) thetemporal alignment of facial expressions. Experimental results on 2 synthetic and 7 real world datasets indicate the robustness and effectiveness of the proposed methodson these application domains, outperforming other state-of the-art methods in the field. PMID- 26552078 TI - Determining the Performance of Fluorescence Molecular Imaging Devices Using Traceable Working Standards With SI Units of Radiance. AB - To date, no emerging preclinical or clinical near-infrared fluorescence (NIRF) imaging devices for noninvasive and/or surgical guidance have their performances validated on working standards with SI units of radiance that enable comparison or quantitative quality assurance. In this work, we developed and deployed a methodology to calibrate a stable, solid phantom for emission radiance with International System of Units (SI) units of mW .sr(-1) .cm(-2) for use in characterizing the measurement sensitivity of ICCD and IsCMOS detection, signal to-noise ratio, and contrast. In addition, at calibrated radiances, we assess transverse and lateral resolution of ICCD and IsCMOS camera systems. The methodology allowed demonstration of superior SNR of the ICCD over the IsCMOS technology and superior resolution of the IsCMOS over the ICCD approach. Contrast depended upon the camera settings (binning and integration time) and gain of intensifier. Finally, because the architecture of CMOS and CCD camera systems results in vastly different performance, we comment on the utility of these technologies for small animal imaging as well as clinical applications for noninvasive and surgical guidance. PMID- 26552079 TI - Improving Optoacoustic Image Quality via Geometric Pixel Super-Resolution Approach. AB - High fidelity optoacoustic (photoacoustic) tomography requires dense spatial sampling of optoacoustic signals using point acoustic detectors. However, in practice, spatial resolution of the images is often limited by limited sampling either due to coarse multi-element arrays or time in raster scan measurements. Herein, we investigate a method that integrates information from multiple optoacoustic images acquired at sub-diffraction steps into one high resolution image by means of an iterative registration algorithm. Experimental validations performed in target phantoms and ex vivo tissue samples confirm that the suggested approach renders significant improvements in terms of optoacoustic image resolution and quality without introducing significant alterations into the signal acquisition hardware or inversion algorithms. PMID- 26552080 TI - Automatic Stem Cell Detection in Microscopic Whole Mouse Cryo-Imaging. AB - With its single cell sensitivity over volumes as large as or larger than a mouse, cryo-imaging enables imaging of stem cell biodistribution, homing, engraftment, and molecular mechanisms. We developed and evaluated a highly automated software tool to detect fluorescently labeled stem cells within very large ( ~ 200 GB) cryo-imaging datasets. Cell detection steps are: preprocess, remove immaterial regions, spatially filter to create features, identify candidate pixels, classify pixels using bagging decision trees, segment cell patches, and perform 3D labeling. There are options for analysis and visualization. To train the classifier, we created synthetic images by placing realistic digital cell models onto cryo-images of control mice devoid of cells. Very good cell detection results were (precision=98.49%, recall=99.97%) for synthetic cryo-images, (precision=97.81%, recall=97.71%) for manually evaluated, actual cryo-images, and false positives in control mice. An alpha-multiplier applied to features allows one to correct for experimental variations in cell brightness due to labeling. On dim cells (37% of standard brightness), with correction, we improved recall (49.26%-> 99.36%) without a significant drop in precision (99.99%-> 99.75%) . With tail vein injection, multipotent adult progenitor cells in a graft-versus host-disease model in the first days post injection were predominantly found in lung, liver, spleen, and bone marrow. Distribution was not simply related to blood flow. The lung contained clusters of cells while other tissues contained single cells. Our methods provided stem cell distribution anywhere in mouse with single cell sensitivity. Methods should provide a rational means of evaluating dosing, delivery methods, cell enhancements, and mechanisms for therapeutic cells. PMID- 26552081 TI - Ultrashort Microwave-Pumped Real-Time Thermoacoustic Breast Tumor Imaging System. AB - We report the design of a real-time thermoacoustic (TA) scanner dedicated to imaging deep breast tumors and investigate its imaging performance. The TA imaging system is composed of an ultrashort microwave pulse generator and a ring transducer array with 384 elements. By vertically scanning the transducer array that encircles the breast phantom, we achieve real-time, 3D thermoacoustic imaging (TAI) with an imaging speed of 16.7 frames per second. The stability of the microwave energy and its distribution in the cling-skin acoustic coupling cup are measured. The results indicate that there is a nearly uniform electromagnetic field in each XY-imaging plane. Three plastic tubes filled with salt water are imaged dynamically to evaluate the real-time performance of our system, followed by 3D imaging of an excised breast tumor embedded in a breast phantom. Finally, to demonstrate the potential for clinical applications, the excised breast of a ewe embedded with an ex vivo human breast tumor is imaged clearly with a contrast of about 1:2.8. The high imaging speed, large field of view, and 3D imaging performance of our dedicated TAI system provide the potential for clinical routine breast screening. PMID- 26552082 TI - An Algorithm for the Segmentation of Highly Abnormal Hearts Using a Generic Statistical Shape Model. AB - Statistical shape models (SSMs) have been widely employed in cardiac image segmentation. However, in conditions that induce severe shape abnormality and remodeling, such as in the case of pulmonary hypertension (PH) or hypertrophic cardiomyopathy (HCM), a single SSM is rarely capable of capturing the anatomical variability in the extremes of the distribution. This work presents a new algorithm for the segmentation of severely abnormal hearts. The algorithm is highly flexible, as it does not require a priori knowledge of the involved pathology or any specific parameter tuning to be applied to the cardiac image under analysis. The fundamental idea is to approximate the gross effect of the abnormality with a virtual remodeling transformation between the patient-specific geometry and the average shape of the reference model (e.g., average normal morphology). To define this mapping, a set of landmark points are automatically identified during boundary point search, by estimating the reliability of the candidate points. With the obtained transformation, the feature points extracted from the patient image volume are then projected onto the space of the reference SSM, where the model is used to effectively constrain and guide the segmentation process. The extracted shape in the reference space is finally propagated back to the original image of the abnormal heart to obtain the final segmentation. Detailed validation with patients diagnosed with PH and HCM shows the robustness and flexibility of the technique for the segmentation of highly abnormal hearts of different pathologies. PMID- 26552083 TI - Allan Variance Computed in Space Domain: Definition and Application to InSAR Data to Characterize Noise and Geophysical Signal. AB - The Allan variance was introduced 50 years ago for analyzing the stability of frequency standards. In addition to its metrological interest, it may be also considered as an estimator of the large trends of the power spectral density (PSD) of frequency deviation. For instance, the Allan variance is able to discriminate different types of noise characterized by different power laws in the PSD. The Allan variance was also used in other fields than time and frequency metrology: for more than 20 years, it has been used in accelerometry, geophysics, geodesy, astrophysics, and even finances. However, it seems that up to now, it has been exclusively applied for time series analysis. We propose here to use the Allan variance on spatial data. Interferometric synthetic aperture radar (InSAR) is used in geophysics to image ground displacements in space [over the synthetic aperture radar (SAR) image spatial coverage] and in time thanks to the regular SAR image acquisitions by dedicated satellites. The main limitation of the technique is the atmospheric disturbances that affect the radar signal while traveling from the sensor to the ground and back. In this paper, we propose to use the Allan variance for analyzing spatial data from InSAR measurements. The Allan variance was computed in XY mode as well as in radial mode for detecting different types of behavior for different space-scales, in the same way as the different types of noise versus the integration time in the classical time and frequency application. We found that radial Allan variance is the more appropriate way to have an estimator insensitive to the spatial axis and we applied it on SAR data acquired over eastern Turkey for the period 2003-2011. Spatial Allan variance allowed us to well characterize noise features, classically found in InSAR such as phase decorrelation producing white noise or atmospheric delays, behaving like a random walk signal. We finally applied the spatial Allan variance to an InSAR time series to detect when the geophysical signal, here the ground motion, emerges from the noise. PMID- 26552084 TI - Adaptive Light Modulation for Improved Resolution and Efficiency in All-Optical Pulse-Echo Ultrasound. AB - In biomedical all-optical pulse-echo ultrasound systems, ultrasound is generated with the photoacoustic effect by illuminating an optically absorbing structure with a temporally modulated light source. Nanosecond range laser pulses are typically used, which can yield bandwidths exceeding 100 MHz. However, acoustical attenuation within tissue or nonuniformities in the detector or source power spectra result in energy loss at the affected frequencies and in a reduced overall system efficiency. In this work, a laser diode is used to generate linear and nonlinear chirp optical modulations that are extended to microsecond time scales, with bandwidths constrained to the system sensitivity. Compared to those obtained using a 2-ns pulsed laser, pulse-echo images of a phantom obtained using linear chirp excitation exhibit similar axial resolution (99 versus 92 MUm, respectively) and signal-to-noise ratios (SNRs) (10.3 versus 9.6 dB). In addition, the axial point spread function (PSF) exhibits lower sidelobe levels in the case of chirp modulation. Using nonlinear (time-stretched) chirp excitations, where the nonlinearity is computed from measurements of the spectral sensitivity of the system, the power spectrum of the imaging system was flattened and its bandwidth broadened. Consequently, the PSF has a narrower axial extent and still lower sidelobe levels. Pulse-echo images acquired with time-stretched chirps as optical modulation have higher axial resolution (64 MUm) than those obtained with linear chirps, at the expense of a lower SNR (6.8 dB). Using a linear or time stretched chirp, the conversion efficiency from optical power to acoustical pressure improved by a factor of 70 or 61, respectively, compared to that obtained with pulsed excitation. PMID- 26552085 TI - A Focused Low-Intensity Pulsed Ultrasound (FLIPUS) System for Cell Stimulation: Physical and Biological Proof of Principle. AB - Quantitative ultrasound (QUS) is a promising technique for bone tissue evaluation. Highly focused transducers used for QUS also have the capability to be applied for tissue-regenerative purposes and can provide spatially limited deposition of acoustic energy. We describe a focused low-intensity pulsed ultrasound (FLIPUS) system, which has been developed for the stimulation of cell monolayers in the defocused far field of the transducer through the bottom of the well plate. Tissue culture well plates, carrying the cells, were incubated in a special chamber, immersed in a temperature-controlled water tank. A stimulation frequency of 3.6 MHz provided an optimal sound transmission through the polystyrene well plate. The ultrasound was pulsed for 20 min daily at 100-Hz repetition frequency with 27.8% duty cycle. The calibrated output intensity corresponded to I(SATA) = 44.5 +/- 7.1 mW/cm2, which is comparable to the most frequently reported nominal output levels in LIPUS studies. No temperature change by the ultrasound exposure was observed in the well plate. The system was used to stimulate rat mesenchymal stem cells (rMSCs). The applied intensity had no apoptotic effect and enhanced the expression of osteogenic markers, i.e., osteopontin (OPN), collagen 1 (Col-1), the osteoblast-specific transcription factor-Runx-2 and E11 protein, an early osteocyte marker, in stimulated cells on day 5. The proposed FLIPUS setup opens new perspectives for the evaluation of the mechanistic effects of LIPUS. PMID- 26552086 TI - Curve-Like Structure Extraction Using Minimal Path Propagation With Backtracking. AB - Minimal path techniques can efficiently extract geometrically curve-like structures by finding the path with minimal accumulated cost between two given endpoints. Though having found wide practical applications (e.g., line identification, crack detection, and vascular centerline extraction), minimal path techniques suffer from some notable problems. The first one is that they require setting two endpoints for each line to be extracted (endpoint problem). The second one is that the connection might fail when the geodesic distance between the two points is much shorter than the desirable minimal path (shortcut problem). In addition, when connecting two distant points, the minimal path connection might become inefficient as the accumulated cost increases over the propagation and results in leakage into some non-feature regions near the starting point (accumulation problem). To address these problems, this paper proposes an approach termed minimal path propagation with backtracking. We found that the information in the process of backtracking from reached points can be well utilized to overcome the above problems and improve the extraction performance. The whole algorithm is robust to parameter setting and allows a coarse setting of the starting point. Extensive experiments with both simulated and realistic data are performed to validate the performance of the proposed method. PMID- 26552087 TI - Texture-Independent Long-Term Tracking Using Virtual Corners. AB - Long-term tracking of an object, given only a single instance in an initial frame, remains an open problem. We propose a visual tracking algorithm, robust to many of the difficulties that often occur in real-world scenes. Correspondences of edge-based features are used, to overcome the reliance on the texture of the tracked object and improve invariance to lighting. Furthermore, we address long term stability, enabling the tracker to recover from drift and to provide redetection following object disappearance or occlusion. The two-module principle is similar to the successful state-of-the-art long-term TLD tracker; however, our approach offers better performance in benchmarks and extends to cases of low textured objects. This becomes obvious in cases of plain objects with no texture at all, where the edge-based approach proves the most beneficial. We perform several different experiments to validate the proposed method. First, results on short-term sequences show the performance of tracking challenging (low textured and/or transparent) objects that represent failure cases for competing the state of-the-art approaches. Second, long sequences are tracked, including one of almost 30 000 frames, which, to the best of our knowledge, is the longest tracking sequence reported to date. This tests the redetection and drift resistance properties of the tracker. Finally, we report the results of the proposed tracker on the VOT Challenge 2013 and 2014 data sets as well as on the VTB1.0 benchmark, and we show relative performance of the tracker compared with its competitors. All the results are comparable with the state of the art on sequences with textured objects and superior on non-textured objects. The new annotated sequences are made publicly available. PMID- 26552088 TI - Enhancing Sketch-Based Image Retrieval by Re-Ranking and Relevance Feedback. AB - A sketch-based image retrieval often needs to optimize the tradeoff between efficiency and precision. Index structures are typically applied to large-scale databases to realize efficient retrievals. However, the performance can be affected by quantization errors. Moreover, the ambiguousness of user-provided examples may also degrade the performance, when compared with traditional image retrieval methods. Sketch-based image retrieval systems that preserve the index structure are challenging. In this paper, we propose an effective sketch-based image retrieval approach with re-ranking and relevance feedback schemes. Our approach makes full use of the semantics in query sketches and the top ranked images of the initial results. We also apply relevance feedback to find more relevant images for the input query sketch. The integration of the two schemes results in mutual benefits and improves the performance of the sketch-based image retrieval. PMID- 26552089 TI - An EEMD-ICA Approach to Enhancing Artifact Rejection for Noisy Multivariate Neural Data. AB - As neural data are generally noisy, artifact rejection is crucial for data preprocessing. It has long been a grand research challenge for an approach which is able: 1) to remove the artifacts and 2) to avoid loss or disruption of the structural information at the same time, thus the risk of introducing bias to data interpretation may be minimized. In this study, an approach (namely EEMD ICA) was proposed to first decompose multivariate neural data that are possibly noisy into intrinsic mode functions (IMFs) using ensemble empirical mode decomposition (EEMD). Independent component analysis (ICA) was then applied to the IMFs to separate the artifactual components. The approach was tested against the classical ICA and the automatic wavelet ICA (AWICA) methods, which were dominant methods for artifact rejection. In order to evaluate the effectiveness of the proposed approach in handling neural data possibly with intensive noises, experiments on artifact removal were performed using semi-simulated data mixed with a variety of noises. Experimental results indicate that the proposed approach continuously outperforms the counterparts in terms of both normalized mean square error (NMSE) and Structure SIMilarity (SSIM). The superiority becomes even greater with the decrease of SNR in all cases, e.g., SSIM of the EEMD-ICA can almost double that of AWICA and triple that of ICA. To further examine the potentials of the approach in sophisticated applications, the approach together with the counterparts were used to preprocess a real-life epileptic EEG with absence seizure. Experiments were carried out with the focus on characterizing the dynamics of the data after artifact rejection, i.e., distinguishing seizure free, pre-seizure and seizure states. Using multi-scale permutation entropy to extract feature and linear discriminant analysis for classification, the EEMD-ICA performed the best for classifying the states (87.4%, about 4.1% and 8.7% higher than that of AWICA and ICA respectively), which was closest to the results of the manually selected dataset (89.7%). PMID- 26552090 TI - Crystalline Bacterial Surface Layer (S-Layer) Opens Golden Opportunities for Nanobiotechnology in Textiles. AB - This study focuses on the successful recrystallization of bacterial S-layer arrays of the Lactobacillus acidophilus ATCC 4356 at textile surfaces to create a novel method and material. Optimum bacterial growth was obtained at approximately 45 degrees C, pH 5.0, and 14 h pi. The cells were resuspended in guanidine hydrochloride and the 43 kDa S-protein was dialyzed and purified. The optimum reassembly on the polypropylene fabric surface in terms of scanning electron microscopy (SEM), reflectance, and uniformity (spectrophotometry) was obtained at 30 degrees C, pH 5.0 for 30 minutes in the presence of 2 gr/l (liquor ratio; 1:40) of the S-protein. Overall, our data showed that the functional aspects and specialty applications of the fabric would be very attractive for the textile and related sciences, and result in advanced technical textiles. PMID- 26552091 TI - A New Method to Predict RNA Secondary Structure Based on RNA Folding Simulation. AB - RNA plays an important role in various biological processes; hence, it is essential when determining the functions of RNA to research its secondary structures. So far, the accuracy of RNA secondary structure prediction remains an area in need of improvement. This paper presents a novel method for predicting RNA secondary structure based on an RNA folding simulation model. This model assumes that the process of RNA folding from the random coil state to full structure is staged and in every stage of folding, the final state of an RNA is determined by the optimal combination of helical regions, which are urgently essential to dynamics of RNA formation. This paper proposes the First Large Free Energy Difference (FLED) in order to find the helical regions most urgently needed for optimal final state formation among all the possible helical regions. Tests on the datasets with known structures from public databases demonstrate that our method can outperform other current RNA secondary structure prediction methods in terms of prediction accuracy. PMID- 26552092 TI - Online Estimation Method for Respiratory Parameters Based on a Pneumatic Model. AB - Mechanical ventilation is an important method to help people breathe. Respiratory parameters of ventilated patients are usually tracked for pulmonary diagnostics and respiratory treatment assessment. In this paper, to improve the estimation accuracy of respiratory parameters, a pneumatic model for mechanical ventilation was proposed. Furthermore, based on the mathematical model, a recursive least squares algorithm was adopted to estimate the respiratory parameters. Finally, through experimental and numerical study, it was demonstrated that the proposed estimation method was effective and the method can be used in pulmonary diagnostics and treatment. PMID- 26552093 TI - A Novel Method Using Abstract Convex Underestimation in Ab-Initio Protein Structure Prediction for Guiding Search in Conformational Feature Space. AB - To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more efficiently obtain the near-native protein structure. PMID- 26552094 TI - A Cooperative Framework for Fireworks Algorithm. AB - This paper presents a cooperative framework for fireworks algorithm (CoFFWA). A detailed analysis of existing fireworks algorithm (FWA) and its recently developed variants has revealed that ( i) the current selection strategy has the drawback that the contribution of the firework with the best fitness (denoted as core firework) overwhelms the contributions of all other fireworks (non-core fireworks) in the explosion operator, ( ii) the Gaussian mutation operator is not as effective as it is designed to be. To overcome these limitations, the CoFFWA is proposed, which significantly improves the exploitation capability by using an independent selection method and also increases the exploration capability by incorporating a crowdness-avoiding cooperative strategy among the fireworks. Experimental results on the CEC2013 benchmark functions indicate that CoFFWA outperforms the state-of-the-art FWA variants, artificial bee colony, differential evolution, and the standard particle swarm optimization SPSO2007/SPSO2011 in terms of convergence performance. PMID- 26552095 TI - Direct Extraction of Tumor Response Based on Ensemble Empirical Mode Decomposition for Image Reconstruction of Early Breast Cancer Detection by UWB. AB - A direct extraction method of tumor response based on ensemble empirical mode decomposition (EEMD) is proposed for early breast cancer detection by ultra-wide band (UWB) microwave imaging. With this approach, the image reconstruction for the tumor detection can be realized with only extracted signals from as-detected waveforms. The calibration process executed in the previous research for obtaining reference waveforms which stand for signals detected from the tumor free model is not required. The correctness of the method is testified by successfully detecting a 4 mm tumor located inside the glandular region in one breast model and by the model located at the interface between the gland and the fat, respectively. The reliability of the method is checked by distinguishing a tumor buried in the glandular tissue whose dielectric constant is 35. The feasibility of the method is confirmed by showing the correct tumor information in both simulation results and experimental results for the realistic 3-D printed breast phantom. PMID- 26552096 TI - Wireless Flexible Smart Bandage for Continuous Monitoring of Wound Oxygenation. AB - Current methods in treating chronic wounds have had limited success in large part due to the open loop nature of the treatment. We have created a localized 3D printed smart wound dressing platform that will allow for real-time data acquisition of oxygen concentration, which is an important indicator of wound healing. This will serve as the first leg of a feedback loop for a fully optimized treatment mechanism tailored to the individual patient. A flexible oxygen sensor was designed and fabricated with high sensitivity and linear current output. With a series of off-the-shelf electronic components including a programmable-gain analog front-end, a microcontroller and wireless radio, an integrated electronic system with data readout and wireless transmission capabilities was assembled in a compact package. Using an elastomeric material, a bandage with exceptional flexibility and tensile strength was 3D-printed. The bandage contains cavities for both the oxygen sensor and the electronic systems, with contacts interfacing the two systems. Our integrated, flexible platform is the first step toward providing a self-operating, highly optimized remote therapy for chronic wounds. PMID- 26552097 TI - Finite-Time State Estimation for Coupled Markovian Neural Networks With Sensor Nonlinearities. AB - This paper investigates the issue of finite-time state estimation for coupled Markovian neural networks subject to sensor nonlinearities, where the Markov chain with partially unknown transition probabilities is considered. A Luenberger type state estimator is proposed based on incomplete measurements, and the estimation error system is derived by using the Kronecker product. By using the Lyapunov method, sufficient conditions are established, which guarantee that the estimation error system is stochastically finite-time bounded and stochastically finite-time stable, respectively. Then, the estimator gains are obtained via solving a set of coupled linear matrix inequalities. Finally, a numerical example is given to illustrate the effectiveness of the proposed new design method. PMID- 26552098 TI - Cloud-Scale Genomic Signals Processing for Robust Large-Scale Cancer Genomic Microarray Data Analysis. AB - As microarray data available to scientists continues to increase in size and complexity, it has become overwhelmingly important to find multiple ways to bring forth oncological inference to the bioinformatics community through the analysis of large-scale cancer genomic (LSCG) DNA and mRNA microarray data that is useful to scientists. Though there have been many attempts to elucidate the issue of bringing forth biological interpretation by means of wavelet preprocessing and classification, there has not been a research effort that focuses on a cloud scale distributed parallel (CSDP) separable 1-D wavelet decomposition technique for denoising through differential expression thresholding and classification of LSCG microarray data. This research presents a novel methodology that utilizes a CSDP separable 1-D method for wavelet-based transformation in order to initialize a threshold which will retain significantly expressed genes through the denoising process for robust classification of cancer patients. Additionally, the overall study was implemented and encompassed within CSDP environment. The utilization of cloud computing and wavelet-based thresholding for denoising was used for the classification of samples within the Global Cancer Map, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas. The results proved that separable 1-D parallel distributed wavelet denoising in the cloud and differential expression thresholding increased the computational performance and enabled the generation of higher quality LSCG microarray datasets, which led to more accurate classification results. PMID- 26552100 TI - Event Detection in Twitter Microblogging. AB - The millions of tweets submitted daily overwhelm users who find it difficult to identify content of interest revealing the need for event detection algorithms in Twitter. Such algorithms are proposed in this paper covering both short (identifying what is currently happening) and long term periods (reviewing the most salient recently submitted events). For both scenarios, we propose fuzzy represented and timely evolved tweet-based theoretic information metrics to model Twitter dynamics. The Riemannian distance is also exploited with respect to words' signatures to minimize temporal effects due to submission delays. Events are detected through a multiassignment graph partitioning algorithm that: 1) optimally retains maximum coherence within a cluster and 2) while allowing a word to belong to several clusters (events). Experimental results on real-life data demonstrate that our approach outperforms other methods. PMID- 26552099 TI - Evaluation of AllergiSense Smartphone Tools for Adrenaline Injection Training. AB - Anaphylaxis is an increasingly prevalent life-threatening allergic condition that requires people with anaphylaxis and their caregivers to be trained in the avoidance of allergen triggers and in the administration of adrenaline autoinjectors. The prompt and correct administration of autoinjectors in the event of an anaphylactic reaction is a significant challenge in the management of anaphylaxis. Unfortunately, many people do not know how to use autoinjectors and either fail to use them or fail to use them correctly. This is due in part to deficiencies in training and also to the lack of a system encouraging continuous practice with feedback. Assistive smartphone healthcare technologies have demonstrated potential to support the management of chronic conditions such as diabetes and cardiovascular disease, but there have been deficiencies in their evaluation and there has been a lack of application to anaphylaxis. This paper describes AllergiSense, a smartphone app and sensing system for anaphylaxis management, and presents the results of a randomized, controlled, prepost evaluation of AllergiSense injection training and feedback tools with healthy participants. Participants whose training was supplemented with AllergiSense injection feedback achieved significantly better practiced injections with 90.5% performing correct injections compared to only 28.6% in the paper-only control group. In addition, the results provide insights into possible self-efficacy failings in traditional training and the benefits of embedding self-efficacy theory into the technology design process. PMID- 26552101 TI - Cooperative Differential Evolution With Multiple Populations for Multiobjective Optimization. AB - This paper presents a cooperative differential evolution (DE) with multiple populations for multiobjective optimization. The proposed algorithm has M single objective optimization subpopulations and an archive population for an M objective optimization problem. An adaptive DE is applied to each subpopulation to optimize the corresponding objective of the multiobjective optimization problem (MOP). The archive population is also optimized by an adaptive DE. The archive population is used not only to maintain all nondominated solutions found so far but also to guide each subpopulation to search along the whole Pareto front. These (M+1) populations cooperate to optimize all objectives of the MOP by using adaptive DEs. Simulation results on benchmark problems with two, three, and many objectives show that the proposed algorithm is better than some state-of-the art multiobjective DE algorithms and other popular multiobjective evolutionary algorithms. The online search behavior and parameter sensitivity of the proposed algorithm are also investigated. PMID- 26552102 TI - Consensus Under Bounded Noise in Discrete Network Systems: An Algorithm With Fast Convergence and High Accuracy. AB - Most existing works investigate consensus with noise following a certain distribution, e.g., Gaussian distribution, with fixed expectation and variance, which may not be satisfied in practical applications. This paper investigates the discrete system consensus under bounded noise, which is important and practical problem. We first provide necessary and sufficient conditions for the convergence of consensus under bounded noise. To be more general, we derive an analytical bound to show the max-min difference between the nodes' states when the general consensus algorithm converges to a stable state. Then, a novel consensus algorithm, fast consensus under bounded noise (FCBN), is proposed to eliminate the accumulative error caused by the bounded noise. It is proved that FCBN has a faster convergence speed and a higher consensus accuracy than general consensus algorithms. Extensive simulations demonstrate the effectiveness of the proposed algorithm. PMID- 26552103 TI - Value Iteration Adaptive Dynamic Programming for Optimal Control of Discrete-Time Nonlinear Systems. AB - In this paper, a value iteration adaptive dynamic programming (ADP) algorithm is developed to solve infinite horizon undiscounted optimal control problems for discrete-time nonlinear systems. The present value iteration ADP algorithm permits an arbitrary positive semi-definite function to initialize the algorithm. A novel convergence analysis is developed to guarantee that the iterative value function converges to the optimal performance index function. Initialized by different initial functions, it is proven that the iterative value function will be monotonically nonincreasing, monotonically nondecreasing, or nonmonotonic and will converge to the optimum. In this paper, for the first time, the admissibility properties of the iterative control laws are developed for value iteration algorithms. It is emphasized that new termination criteria are established to guarantee the effectiveness of the iterative control laws. Neural networks are used to approximate the iterative value function and compute the iterative control law, respectively, for facilitating the implementation of the iterative ADP algorithm. Finally, two simulation examples are given to illustrate the performance of the present method. PMID- 26552104 TI - Extreme Learning Machine With Subnetwork Hidden Nodes for Regression and Classification. AB - As demonstrated earlier, the learning effectiveness and learning speed of single hidden-layer feedforward neural networks are in general far slower than required, which has been a major bottleneck for many applications. Huang et al. proposed extreme learning machine (ELM) which improves the training speed by hundreds of times as compared to its predecessor learning techniques. This paper offers an ELM-based learning method that can grow subnetwork hidden nodes by pulling back residual network error to the hidden layer. Furthermore, the proposed method provides a similar or better generalization performance with remarkably fewer hidden nodes as compared to other ELM methods employing huge number of hidden nodes. Thus, the learning speed of the proposed technique is hundred times faster compared to other ELMs as well as to back propagation and support vector machines. The experimental validations for all methods are carried out on 32 data sets. PMID- 26552105 TI - Promoting Interactions Between Humans and Robots Using Robotic Emotional Behavior. AB - The objective of a socially assistive robot is to create a close and effective interaction with a human user for the purpose of giving assistance. In particular, the social interaction, guidance, and support that a socially assistive robot can provide a person can be very beneficial to patient-centered care. However, there are a number of research issues that need to be addressed in order to design such robots. This paper focuses on developing effective emotion based assistive behavior for a socially assistive robot intended for natural human-robot interaction (HRI) scenarios with explicit social and assistive task functionalities. In particular, in this paper, a unique emotional behavior module is presented and implemented in a learning-based control architecture for assistive HRI. The module is utilized to determine the appropriate emotions of the robot to display, as motivated by the well-being of the person, during assistive task-driven interactions in order to elicit suitable actions from users to accomplish a given person-centered assistive task. A novel online updating technique is used in order to allow the emotional model to adapt to new people and scenarios. Experiments presented show the effectiveness of utilizing robotic emotional assistive behavior during HRI scenarios. PMID- 26552106 TI - Good Practices for Learning to Recognize Actions Using FV and VLAD. AB - High dimensional representations such as Fisher vectors (FV) and vectors of locally aggregated descriptors (VLAD) have shown state-of-the-art accuracy for action recognition in videos. The high dimensionality, on the other hand, also causes computational difficulties when scaling up to large-scale video data. This paper makes three lines of contributions to learning to recognize actions using high dimensional representations. First, we reviewed several existing techniques that improve upon FV or VLAD in image classification, and performed extensive empirical evaluations to assess their applicability for action recognition. Our analyses of these empirical results show that normality and bimodality are essential to achieve high accuracy. Second, we proposed a new pooling strategy for VLAD and three simple, efficient, and effective transformations for both FV and VLAD. Both proposed methods have shown higher accuracy than the original FV/VLAD method in extensive evaluations. Third, we proposed and evaluated new feature selection and compression methods for the FV and VLAD representations. This strategy uses only 4% of the storage of the original representation, but achieves comparable or even higher accuracy. Based on these contributions, we recommend a set of good practices for action recognition in videos for practitioners in this field. PMID- 26552107 TI - Doctor Bakhshalian Responds. PMID- 26552108 TI - Zika virus outbreaks in the Americas. PMID- 26552109 TI - Malaria situation, 2015. PMID- 26552110 TI - Exempting Mental Health Peer Support Services From Copayments. Direct final rule; confirmation of effective date. AB - The Department of Veterans Affairs (VA) published a direct final rule amending its regulation that governs VA services that are not subject to copayment requirements for inpatient hospital care or outpatient medical care. Specifically, the regulation is amended to exempt mental health peer support services from having any required copayment. VA received no adverse comments concerning the direct final rule or its companion substantially identical proposed rule published in the Federal Register on the same date. This document confirms that the direct final rule became effective on January 27, 2015. In a companion document in this issue of the Federal Register, we are withdrawing as unnecessary the proposed rule. PMID- 26552111 TI - Medicare and Medicaid Programs; CY 2016 Home Health Prospective Payment System Rate Update; Home Health Value-Based Purchasing Model; and Home Health Quality Reporting Requirements. Final rule. AB - This final rule will update Home Health Prospective Payment System (HH PPS) rates, including the national, standardized 60-day episode payment rates, the national per-visit rates, and the non-routine medical supply (NRS) conversion factor under the Medicare prospective payment system for home health agencies (HHAs), effective for episodes ending on or after January 1, 2016. As required by the Affordable Care Act, this rule implements the 3rd year of the 4-year phase-in of the rebasing adjustments to the HH PPS payment rates. This rule updates the HH PPS case-mix weights using the most current, complete data available at the time of rulemaking and provides a clarification regarding the use of the "initial encounter'' seventh character applicable to certain ICD-10-CM code categories. This final rule will also finalize reductions to the national, standardized 60 day episode payment rate in CY 2016, CY 2017, and CY 2018 of 0.97 percent in each year to account for estimated case-mix growth unrelated to increases in patient acuity (nominal case-mix growth) between CY 2012 and CY 2014. In addition, this rule implements a HH value-based purchasing (HHVBP) model, beginning January 1, 2016, in which all Medicare-certified HHAs in selected states will be required to participate. Finally, this rule finalizes minor changes to the home health quality reporting program and minor technical regulations text changes. PMID- 26552112 TI - Medicare Program; End-Stage Renal Disease Prospective Payment System, and Quality Incentive Program. Final Rule. AB - This rule updates and makes revisions to the End-Stage Renal Disease (ESRD) Prospective Payment System (PPS) for calendar year (CY) 2016. This rule is necessary to ensure that ESRD facilities receive accurate Medicare payment amounts for furnishing outpatient maintenance dialysis treatments during calendar year 2016. This rule will also set forth requirements for the ESRD Quality Incentive Program (QIP), including for PYs 2017 through 2019. PMID- 26552113 TI - Margaret (Peggy) Wheelock (1945-2009): cell scientist, mentor and friend. PMID- 26552114 TI - Evidence appraisal of Brock AS, Steed LL, Freeman J, Garry B, Malpas P, Cotton P. Endoscope storage time: assessment of microbial colonization up to 21 days after reprocessing. PMID- 26552115 TI - National Preparedness Month: opportunities for nurse engagement. PMID- 26552117 TI - The value of music therapy in patient care. PMID- 26552116 TI - Preparing for respiratory disease outbreaks. PMID- 26552118 TI - [Ebola Virus Disease Outbreak Response in West Africa]. AB - The largest ever outbreak of Ebola virus disease has been spreading in West Africa. The authors were deployed to Liberia and Sierra Leone as short-term consultants for the World Health Organization. Our mission was to ensure clinical management and infection prevention and control priorities in frontline treatment centres. This paper describes how the disease is spread, its symptoms and progression, measures currently taken to ensure both infection control and the best possible care, and the significance of infections among health care workers. We adopted an approach which is detailed in the WHO Clinical Management of Patients with Viral Haemorrhagic Fever. Areas within the treatment centres were divided into either a "hot zone" or a "cold zone". Patients were interviewed, and those patients who met the criteria for suspected, probable or confirmed cases were moved to hot zones. All health care workers wore personal protective equipment when entering a hot zone and washed hands with a hypochlorite solution after each patient encounter. Among the problems which we encountered was a fundamental mismatch in the numbers of patients and nurses. The nurses often had to work alone in hot zones in protective equipment which limited physical movement and blurred vision. These factors contributed to fatigue due to prolonged outbreak response and may have resulted in infections among the nursing staff. In conclusion, we present the current situation in West Africa in regard to the recent outbreak of Ebola virus disease, specifically the clinical picture based on our observation. We further propose steps to be taken to handle the patient care safely and effectively. We hope our experience will contribute to national discussions on how to respond to the Ebola virus disease. PMID- 26552119 TI - [Evaluation of Norovirus Detection Method Based on a Newly Developed Bioluminescent Enzyme Immunoassay (BLEIA) System]. AB - Noroviruses (NoV) are a major cause of nonbacterial acute gastroenteritis. To efficiently control NoV infection, preventing the transmission of the virus from NoV-infected food-handlers to food may be crucial. At present, reverse transcription real-time PCR (rRT-PCR) methods may be used as a sensitive method to detect NoV, but the method has the drawbacks of being expensive and time consuming. Other conventional immunological methods such as ELISA and immuno chromatographic tests are more economical and easier to use than rRT-PCR, but these methods may not be highly sensitive. To overcome these problems, we have developed a novel bioluminescent enzyme immunoassay (BLEIA) system. The system is fully automated and this may enable the rapid, highly sensitive detection of NoV. To practically evaluate the BLEIA, we measured a number of fecal specimens from the patients with acute-gastroenteritis due to NoV infection or healthy adult volunteers in Japan. The performance of the BLEIA was compared with the Loop Mediated Isothermal Amplification (LAMP) assay and rRT-PCR. The sensitivity, specificity, and correspondence rate of the BLEIA were 93.1% (135/145), 100% (87/87), and 95.7% (222/232), respectively, and those of the LAMP assay were 91.0% (132/145), 98.9% (86/87), and 94.0% (218/232), respectively. A good correlation (r = 0.72) was obtained between the virus loads measured using rRT PCR and the cut-off index values of the BLEIA, and the sensitivity of the BLEIA was estimated to be 10(5)-10(6) copies/g stool samples. No cross-reactivity toward other closely related or enteric viruses was found. The results indicated that the BLEIA may be applicable for the conventional screening for NoV detection with a large number of fecal specimens from the patients and food-handlers. PMID- 26552120 TI - [Analysis of Non-serotype b Encapsulated Haemophilus influenzae Isolated from Pediatric Patients]. AB - We analyzed non-serotype b encapsulated Haemophilus influenzae (non-b Hi) isolated from pediatric patients at Chiba Children's Hospital during 2000-2012. Among 3,532 clinical isolates of H. influenzae, there were 57 (1.6%) strains of non-b Hi, 152 (4.3%) of serotype b H. influenzae (Hib), and 3,323 (94.1%) of non typeable H. influenzae (NTHi). Fifty-seven strains of non-b Hi were serotyped useing the slide agglutination test and PCR. Twenty-nine strains were identified as type e (Hie) and 28 as type f (Hif), and the results according to the slide agglutination test and PCR were completely identical. Whereas 52 of 57 strains (91.2%) were isolated from respiratory specimen, only one Hif strain (1.8%) was isolated from a sterile site. There were 47 (82.4%) beta-lactamase-non-producing ampicillin (ABPC)-sensitive strains (BLNAS), 5 (8.8%) beta-lactamase-producing strains (BLP), and only 1 (1.8%) beta-lactamase-non-producing ABPC-resistant strain (BLNAR). Thus the frequency of non-b Hi was lower than that of Hib. The source of non-b Hi was similar to that of NTHi, which was mainly isolated from respiratory specimen. Antimicrobial resistant pattern of non-b Hi was different from that of Hib in which the frequency of BLP was relatively high, and NTHi in which that of BLNAR was high. An increase of invasive H. influenzae infections caused by NTHi, Hie, and Hif was reported in the countries where Hib vaccine had been widely used. Because it is assumed that invasive non-Hib infection will be predominant in the near future in Japan, serotyping of invasive strains is crucial. Continuous monitoring of distribution of non-b Hi in the clinical isolates of H. influenzae is also important. PMID- 26552121 TI - [Antimicrobial Susceptibility and Resistance Mutations in Campylobacter jejuni and C. coli Isolates from Human and Meat Sources]. AB - Recently, there has been a marked increase in the number of reports of fluoroquinolone-resistant Campylobacter jejuni and Campylobacter coli. The aim of this study was to evaluate the prevalence of antimicrobial resistance and its genetic determinants in Campylobacter species isolated from meat and human subjects in Fukuoka Prefecture, Japan. Between 2011 and 2013, 55 and 64 isolates were collected from meat (chicken meat and beef liver) and humans, respectively, in this prefecture. Antimicrobial susceptibility tests were conducted using the agar dilution method in accordance with the Clinical and Laboratory Standards Institute guidelines, using the following 11 antimicrobial agents : cephalexin, cefoxitin, nalidixic acid, ciprofloxacin, levofloxacin, tetracycline, minocycline, ampicillin, streptomycin, kanamycin and erythromycin. The susceptibility rates of the isolates to three quinolones (nalidixic acid, ciprofloxacin, levofloxacin) were 43.7%, 41.2%, 40.3%, respectively. All the isolates were multidrug resistant. Whereas 46.9%-51.6% of the human isolates were resistant to one or more of the quinolones, only 32.7%-34.5% of the meat isolates were resistant to one or more of the drugs. DNA sequencing showed that of the 50 quinolone resistant isolates 44 had position 86 isoleucine (Ile) substituted for threonine (Thr) in the GyrA protein (Thr86Ile). This amino acid substitution resulted from ACA to ATA and ACT to ATT mutations of codon 86 in C. jejuni and C. coli, respectively. Furthermore, two of the four C. jejuni isolates lacking the Thr86Ile mutation had combined Ser22Gly-Asn203Ser substitutions, while the remaining two isolates had combined Ser22Gly-Asn203Ser-Ala 206Val substitutions. These four isolates also had cmeABC sequences that differed from the quinolone sensitive C. jejuni ATCC33560(T) strain. In conclusion, C. jejuni and C. coli have relatively high quinolone resistance, and are resistant to other antibiotics. The new combination of amino acid substitutions in the GyrA protein could pose a potential threat to public health in Japan. PMID- 26552122 TI - [The Usefulness of the Scan with 67Ga-citrate to Assess the Therapeutic Effect on Pneumocystis pneumonia with HIV-1 Infection]. AB - OBJECTIVE: Peumocystis pneumonia (PCP) is one of the common opportunistic infections with severe respiratory failure, and is sometimes life-threatening in patients with the acquired immunodeficiency syndrome. Although treatment for PCP is established, an appropriate treatment period has not been evaluated to clarify the risk factors for immune reconstitution inflammatory syndrome (IRIS) associated with PCP. METHOD: We retrospectively analyzed the clinical characteristics of risk factor, which are the treatment period for PCP, and 67Ga scintigraphy (Ga-S) at the 21st day from the start of the treatment for PCP, with 21 cases of PCP and HIV infection treated during 2005-2012 at Kyushu Medical Center. RESULT: The rate of residual uptake by Ga-S was assessed in 17 cases (81%). Four cases were diagnosed as being PCP-IRIS, and residual uptake by Ga-S was detected in all PCP-IRIS cases. The durations of the therapy were classified into three groups: 21 days, 28 days, and 35 days. All PCP-IRIS cases were treated in the period of 28 days. In contrast, in 11 cases that showed residual uptake by Ga-S, and were treated for PCP in 35 days, PCP-IRIS did not occur. Additionally, there were 4 cases in which residual uptake by Ga-S did not occur. They were treated with PCP for only 21 days, but did not show PCP-IRIS. CONCLUSION: In this study, we showed that Ga-S is useful to evaluate the therapeutic effect. Furthermore, we found that the occurrence of PCP-IRIS could be prevented with the early start of cART after 21 days treatment for PCP, when residual uptake by Ga-S after the first treatment for PCP was not detected. It may also be possible to start cART in the early phase after its treatment without the occurrence of PCP IRIS with the appropriate additional treatment of PCP for 14 days. These guidelines for treatment of PCP in HIV-infected adults and adolescents have been recommended for the duration of 21 days since 1984. We propose that for the prevention of PCP-IRIS, it is nessecory to reconsider recommendation for the treatment duration of 21 days, and meanwhile to evaluate the treatment effect of PCP with Ga-S, because PCP resistance to sulfa drugs, namely are trimethoprim sulfamethoxazole, is beginning to appear. PMID- 26552123 TI - [A Case of Disseminated Mycobacterium genavense Infection in an AIDS Patient. A Case Report and a Review of the Literature]. AB - A 44-year-old male, who was HIV seropositive, developped weight loss, high grade fever, and multiple lymphadenopathies. Bone marrow biopsy revealed a granuloma lesion, and at the same part of the specimen, Ziehl Neelsen staining showed multiple mycobacterium diffusely arranged in the histocytes. The culture did not show positive after 6 to 8 weeks. Finally we diagnosed disseminated Mycobacterium genavense using a house-keeping gene analysis including 16S rRNA sequencing of lymph punctate with fine needle aspiration and the specimen from the biopsy of the lymph node. If a specimen tests positive for Ziehl Neelsen staining smear positive, culture negative, and PCR negative for tuberculosis and Mycobacterium avium complex, we should consider M. genavense infection as one of the differential diagnoses. PMID- 26552124 TI - [A Case Strongly Suspected of Being Pulmonary Toxocariasis Showing Multiple Pulmonary Nodules with a Disappearing and Reappearing Halo Sign]. AB - We report herein on a case strongly suspected of being pulmonary toxocariasis. A 22-year-old Indonesian man referred to our hospital presented with abnormal chest shadows upon medical examination. He had no symptoms. He did not have any pets nor did he eat raw beef or chicken. Hematological examination revealed eosinophilia and elevation of IgE. Chest computed tomography revealed 3 pulmonary nodules with the halo sign. We suspected a parasite infection and performed antiparasite antibody testing. Ascaris suum was slightly positive on the screening test. As specific antibody against the larval excretory-secretory products of Toxocara canis, measured at the National Institute of Infectious Diseases, was positive (level 3 up to 8). Subsequently, the abnormal chest shadows disappeared. However, two months later, 2 pulmonary nodules with the halo sign reappeared in other places. Diagnostic therapy with albendazole was performed for 8 weeks. Mild hepatic impairment emerged during therapy, but it was within the allowed range. Thereafter, the results improved for the imaging findings, eosinophilia, serum IgE level, and specific antibody. The antibody level became negative two months after the treatment had ended. We should consider toxocariasis in the differential diagnosis of migratory nodular shadows with the halo sign on chest computed tomography, and immunoserological testing is useful for the diagnosis. PMID- 26552125 TI - [Three Cases of Tsutsugamushi Disease in Miyakojima Island, Okinawa, Japan]. AB - Tsutsugamushi disease (Scrub thyphus) has been reported from all over Japan except the Hokkaido area. In Okinawa, only one patient was reported in 2001, who was infected outside Okinawa Prefecture. The first case infected in Okinawa was reported at Miyakojima Island in 2008. We report herein on the second case diagnosed in 2010, and the third and fourth in 2011, and all three patients were suspected to have been infected at Ikemajima Island adjacent to the island of Miyakojima. The patients recovered without any severe complications after antibiotic therapy with tetracyclines. We should take Tsutsugamushi disease into consideration in the differential diagnosis for a patient with fever, skin rash, and/or eschar even in the Okinawa area. Implementation of appropriate information and education about the disease should be carried out for local residents and tourists. PMID- 26552126 TI - [A Case of Bacteremia Which Followed a Urinary Tract Infection by Oligella urethralis]. AB - An 82-year-old bedridden man with sequelae from a cerebral infarction was admitted to a welfare institution for the elderly. He developed a high fever and hematuria and was prescribed levofloxacin for the treatment of a suspected urinary tract infection. Although his condition improved, the symptoms subsequently recurred; therefore, levofloxacin was again administered. He remained febrile and was admitted to a hospital due to recalcitrant urinary tract infection. Immediately after admission, he developed ischuria and pyuria. Urine and blood cultures at admission indicated the presence of levofloxacin-resistant Oligella urethralis (O. urethralis). He recovered with ceftriaxone medication. To our knowledge, this is the first report of bacteremia associated with a urinary tract infection caused by O. urethralis in Japan. PMID- 26552127 TI - [A Case of Dengue Fever and Subsequent Long-lasting Depression Accompanied by Alopecia in a Japanese Traveler Returning from Bali, Indonesia]. AB - Recovery from dengue fever is generally rapid and uneventful. However, recuperation is often prolonged and may be accompanied by noticeable depression. We present herein on a traveler to Indonesia who developed long-lasting depression after the classic symptoms of dengue fever such as fever, arthralgia, and macropapular rash had resolved. A previously healthy 42-year old japanese woman presented to the Travel Clinic of Seirei Yokohama Hospital with complaints of 4 days of fever, joint aches, bone pain, and a macropapular rash on her torso. She had returned from Bali 5 days previously. During her 1-week stay, one day was spent in rural, mountainous areas where she was exposed to several mosquito bites. The 1st serum sample collected 4 days after the disease onset gave positive result in the rapid dengue IgM antibody test and the rapid dengue NS1 antigen immunechromatographic test. The DENV-1 genome was detected with RT-PCR. Her 13-year old son, who had accompanied her, was also diagnosed as having dengue fever and he recovered without event. The Above-mentioned symptoms resolved within one week. However, the patient suffered from prolonged depression. She also noticed loss of hair 3 months after the disease onset Administration of a Serotonin-Noradrenalin Reuptake Inhibitor and a minor tranquillizer required to allow her requied to lead a normal life. Although she gradually felt better, it took approximately 2 years until she had recovered completely without taking any antidepressant and minor tranquillizer. It is a well-known fact in endemic countries that dengue fever could have an significant impact on the patients' mental well-being. However, it appears that physicians in non-endemic countries are not fully aware of the prolonged depression, which can occur subsequent to the acute illness. Follow-up consultations of returing travelers who have recoverd from dengu fever should be arranged to monitor their mental and emotional states closely. PMID- 26552128 TI - [Homologous Analysis Using Repetitive-sequence-based PCR Typing of Exfoliative Toxin-producing Staphylococcus aureus Isolated from Our Hospital]. AB - We examined staphylococcal coagulase types and homologous analysis using the DiversiLab repetitive-sequence-based PCR system in exfoliative toxin (ET) producing Staphylococcus aureus. Twenty-two isolates (17 methicillin-sensitive Staphylococcus aureus (MSSA) and 5 methicillin-resistant Staphylococcus aureus (MRSA) isolates) obtained in our hospital from January 2012 and December 2013 were used. Three groups were classified according to the coagulase types and serotypes of ET. The first group (4 MSSA) showed coagulase type I and ET-A, and the second group (3 MSSA and 2 MRSA) showed coagulase type I and ET-B. The third group (10 MSSA and 3 MRSA) showed coagulase type V and ET-B. An analysis by DiversiLab demonstrated that homology was high in both the first and second groups. The homogenousness was high among the third group isolates except for the ocular isolates. In our hospital, three important groups were present according to a coagulase type and an ET type, and the homology of ocular isolates could be different from other materials isolates. PMID- 26552129 TI - [Detection and Serotyping of Streptococcus pneumoniae Carried in Healthy Adults with a Modified PCR Method]. AB - Detection of Streptococcus pneumoniae colonized in the pharynx of healthy carriers currently relies on conventional culture methods of direct plating with pharyngeal swab specimens. The accurate measurement of the carriage of pneumococci, however, has not been necessarily achieved with these methods due to low density colonization and contamination of numerous oral streptococci that express alpha-hemolysis. A PCR-based detection method of pneumococci-specific for lytA as well as PCR serotyping of S. pneumoniae was recently developed and their effectiveness was confirmed. We modified the reaction conditions of these methods to improve the detection rate and applied them to the measurement of S. pneumoniae carried in healthy adults. Pharyngeal swab specimens obtained from 110 healthy volunteers over 40 and living in Nagoya were enriched for 5 hours with broth medium supplemented with rabbit serum and the template DNA for PCR was extracted from the mixed enriched culture. Of 110 specimens 36 (32.7%) were lytA positive, the rate of which was much higher than the results of previous culture based studies. The DNA template preparations were then used for PCR-based serotyping with primers specific for each of the types included in pneumococcal 23 valent vaccine (PPV23). We found that 28 out of 36 lytA-positive carriers were identified as being positive for the serotypes belonging to PPV23, although serotypes 6A and 6B were indistinguishable with the PCR method. The most frequent serotype was serotype 14, and serotypes 4, 18C, and 6A/B were also frequently identified. Five lytA-positive carriers were previously vaccinated with PPV23, and among them, 4 were positive for serotypes contained in PPV23. We recommend PCR-based identification and serotyping of S. pneumoniae in broth enrichment culture of pharyngeal swab specimens as a reliable method for the surveillance of healthy carriers with low density colonization. PMID- 26552130 TI - [Clinical Features of Hospitalized Cases due to Influenza Virus A Infection in the 2011/2012 Season]. AB - In the 2011/2012 season, 18 patients were admitted to our hospital due to influenza virus A infection and the number had increased compared to the previous 3 years (average 5.3 patients/year). Therefore we evaluated the clinical characteristics, treatment, and prognosis of hospitalized cases. Although there were many reports on viral pneumonia caused by influenza (H1N1) 2009 among the young population in the 2009/ 2010 season, 16 out of 18 hospitalized patients were over 65 years-old in the 2011/2012 season. Major causes of admission were pneumonia in 8 cases, heart failure in 5 cases and bronchial asthma attack in 3 cases. The average age of 9 patients with pneumonia was higher significantly compared to 9 patients without pneumonia (average age 85.3 +/- 10.2 : 71.4 +/- 16.1, p < 0.05). Influenza vaccination was performed in 11 patients in total, and 6 out of 9 patients with pneumonia. The interval from illness onset to administration of neuraminidase inhibitors was 1.8 +/- 1.1 days in cases with pneumonia and 2.1 +/- 1.5 days in cases without pneumonia. Though 17 patients got well, one patient died from aspiration pneumonia after recovering from influenza A infection. In the 2011/2012 season, although many patients who had received vaccination needed to be hospitalized because of influenza A infection, the prognosis was fairly good. PMID- 26552131 TI - [Association between Diarrheal Infectious Diseases and Antidiarrheal Drugs Assessed with Prescription Surveillance]. AB - OBJECT: It appears to be possible to measure the outbreak of infectious diseases with accompanying diarrhea by early detection of an outbreak. However, because some diseases are reported weekly from sentinel medical institutions, early detection of outbreaks might be inadequate. In this study, we examined the number of patients with diarrhea assessed with prescription surveillance and validated its association with the number of patients who have infectious diseases with diarrhea. METHODS: The number of patients who were prescribed an antidiarrheal drug or intestinal drug was estimated for each prefecture using the prescription surveillance system from April 1, 2011 through March 31, 2014. Moreover, we examined the association between the prevalence of diarrhea in prescription surveillance and the number of patients with diarrheal infectious diseases. RESULTS: Results showed a positive correlation between the prevalence of diarrhea in prescription surveillance and the number of reported cases per sentinel with gastrointestinal infections. However, no positive correlation was found with the others infectious diseases. CONCLUSION: Estimation of the number of patients with diarrhea in prescription surveillance might facilitate early detection of an outbreak of gastrointestinal infections. PMID- 26552133 TI - [Invasive Aspergillosis Accompanied by a Subcutaneous Nodular Lesion]. AB - We report herein on a case of invasive aspergillosis accompanied by a subcutaneous nodular lesion. A 74-years-old male with myelodysplastic syndrome was hospitalized due to high fever and a painful subcutaneous nodule on the left thigh. Chest radiography and CT scans showed multiple nodular lesions of both lungs, and bacterial pneumonia was initially suspected. He was treated with meropenem, but the symptoms did not subside. Three days after admission, we found that beta-D-glucan levels were elevated at 52.6 pg/mL. He was treated with liposomal amphotericin B (L-AMB) for invasive fungal pneumonia, and the symptoms regressed thereafter. Excisional biopsy of the nodular lesion showed a cluster of septated and branching hyphae. Serum Aspergillus antigen tests and sputum fungal culture were negative, and the fungal species could not be identified. Thus, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) with the excised subcutaneous specimens, and as a result Aspergillus fumigatus infection was diagnosed. Invasive aspergillosis with a subcutaneous lesion is a rare case, and we found that treatment with L-AMB was effective. ISH, PCR and measurement of serum trough concentration of AMPH-B are useful in diagnosis and treatment. PMID- 26552132 TI - [Evaluation of a Rapid Antigen Detection Kit Targeting L7/L12 Ribosomal Protein for Mycoplasma pneumoniae]. AB - We evaluated the usefulness of a rapid antigen detection assay for L7/L12 ribosomal protein (Ribotest Mycoplasma; Asahi Kasei Pharma) for diagnosis of Mycoplasma pneumoniae (M. pneumoniae) infection. Nasopharyngeal swabs were obtained from patients with pneumonia and/or bronchitis; real-time PCR and the L 7/L12 antigen assays were performed with each sample. Serum was also taken from each patient, and the particle agglutination (PA) method was used to detect anti M. pneumoniae antibody in these samples. Macrolide-resistance genes were detected and M. pneumoniae P1 protein subtyping was performed on PCR-positive samples. PCR assays were positive for 85 of 212 specimens (40.1%). Sensitivity and specificity of the L7/L12 antigen assays relative to the PCR standard were 74.1% (63/85) and 81.1% (103/127), respectively. For PCR-positive specimens with a large quantity of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be high. In PCR-positive specimens with fewer than 1.0 x 10(6) copies/mL of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be low. When the PA method was used as the standard, the relative sensitivity and specificity of the L7/L12 antigen assays were 41.7% (5/12) and 75.3% (58/77), respectively, for single serum and 60.9% (14/23) and 85.7% (18/21), respectively, for paired sera. The macrolide-resistance gene A2063G was detected in 20 of the 30 tested PCR-positive specimens (66.7%). Of these 20 A2063G-positive specimens, 13 (65.0%) were positive for the L7/L12 antigen assays. Tne numbers of M. pneumoniae P1 subtypes were as follows: types I (22), IIa(2), IIc(1), and untypable (5). The L7/L12 antigen assays gave positive results for 17 of 21 (81.0%) subtype I, 1 of 2 (50.0%) IIa, and 1 of 1(100%) IIc specimens. PMID- 26552134 TI - [A Serious Case of Pseudomembranous Colitis in which Treatment with Endoscopic Vancomycin Sprinkling Got a Good Result]. AB - We report herein on a 71-year-old man who developed pseudomembranous colitis (PMC). He was treated with oral metronidazole and vancomycin prescription, but deteriorated, and developed a toxic megacolon. Under paralytic ileus condition, per os and enema treatment efficacy was thought to be limited. Sprinkling with vancomycin via colonoscopy was therefore performed, resulting in therapeutic success. Additionally, participation in infection control should be carried out with severe PMC cases like this. PMID- 26552136 TI - [A Case of Acute Respiratory Distress Syndrome (ARDS) Accompanied with Influenza (H1N1) 2009 Successfully Treated with Polymyxin B-immobilized Fiber Column-direct Hemoperfusion (PMX-DHP)]. AB - A 51-year-old man was admitted to our hospital because of fever and diarrhea. Chest X-ray revealed consolidation in the left lower lung field. Ceftriaxone and minocycline were given empirically, under the suspicion of bacterial or atypical pneumonia. In spite of treatment with antibiotics, the disease rapidly progressed to systemic inflammatory response syndrome. The diagnosis of acute respiratory distress syndrome (ARDS) accompanied with influenza (H1N1) 2009 was made because of positive findings of real-time polymerase chain reaction. While multidisciplinary treatment was performed, his condition was further deteriorated suggesting the excessive pro-inflammatory mediators. To remove them, we conducted polymyxin-B immobilized column-direct hemoperfusion (PMX-DHP), and his general condition recovered successfully. PMX-DHP may be a useful treatment choice for ARDS accompanied with influenza. PMID- 26552135 TI - [A Case of Disseminated Cutaneous Mycobacterium chelonae Infection Successfully Improved with Thermal Therapy]. AB - A 54-year-old female with dermatomyositis treated with cyclosporine and methylprednisolone presented with multiple subcutaneous nodules on her upper and lower extremities on December 2011. The number of lesions gradually increased. She had a history of surgical intervention such as debridement, skin graft of right lower leg due to trauma and subsequent bacterial infection on August 2011. Culture from a skin lesion on June 2012 confirmed Mycobacterium chelonae, which was susceptible to clarithromycin (CAM). We started treatment with CAM, imipenem/cilastatin (IPM/CS) and tobramycin (TOB) for 2 weeks. Then CAM monotherapy was continued, however CAM was discontinued because of liver dysfunction. In September 2012 new nodular lesions were observed on the left arm and right leg. We administrated azithromycin, IPM/CS and TOB. Subcutaneous nodules were partially improved, but new lesions appeared on her right leg. A culture of skin lesion yielded M. chelonae, which was highly resistant to CAM and IPM/CS. Based on the sensitivity test, moxifloxacin was used. However, there was no significant improvement in her skin lesions, so we started thermal therapy on day 57 after admission. She showed an excellent response to thermal therapy, and there has been no recurrence. PMID- 26552137 TI - [Direct Identification Results from Positive Blood Culture Bottles Using MALDI TOF MS]. PMID- 26552138 TI - [The mechanisms of drug resistance in prostate cancer]. AB - Drug therapy is one of the efficient methods for prostate cancer treatment. However, drug resistance greatly hindered the treatment of prostate cancer patients. Herein, the mechanisms of drug resistance in prostate cancer have been exhaustively reviewed, and that can provide an alternative strategy and new targets for anti-prostate cancer therapy. PMID- 26552139 TI - [Research progress of IgG4 in isotype selection of antibody drugs]. AB - Many specific therapeutic antibody drugs have been developed for different indications. In drug development, it has been found that the antibody isotype framework can not only affect the physical and chemical properties of therapeutic antibodies, but also influence the activity and therapeutic effect. As a result, IgG isotype selection should be considered carefully in antibody drug development strategies. Because of the unique biological characteristics, IgG4 isotype has been used in some therapeutic antibodies for which effector functions are not desired. In order to provide new ideas for the development of antibody drugs, the research and application progress of IgG4 isotype in therapeutic antibody drug development has been reviewed. PMID- 26552140 TI - [Eukaryotic elongation factor 2 kinase and cancer]. AB - Eukaryotic elongation factor 2 kinase (eEF2K) is well known as a Ca2+/calmodulin (CaM)-dependent kinase. eEF2K catalyzes the phosphorylation of eEF2 and subsequently inactivates eEF2 by impairing its ability to bind to the ribosome, thereby negatively modulates protein synthesis. The high expression of eEF2K has been found recently in several types of malignancies. As participating in the progress of tumor, eEF2K emerges a potential target for future cancer therapy. The relationship between eEF2K and tumor, and the latest progress of eEF2K inhibitors were summarized in this article. PMID- 26552141 TI - [Recent progress of dry powder inhalation of proteins and peptides]. AB - To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder. PMID- 26552142 TI - [m-Nisodipine inhibited 5-HT-induced proliferation of rat PASMCs through Rho/ROCK signal pathway]. AB - This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT (1 umol . L(-1)) treatment for 12-72 h significantly induced the proliferation of rat PASMCs (P<0.05 or P < 0.01), which were inhibited by m-Nis (1 x 10(-5), 1 x 10( 6), l x 10(-7), 1 x10(-8) mol . L(-1)) in dose-dependent manners (P < 0.05 or P < 0.01). Similarly, the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees (P < 0.05 or P < 0.01). Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway. PMID- 26552143 TI - [The action mechanisms of Morus alba leaves extract for the treatment of diabetes based on plasma metabolomics]. AB - In order to evaluate the effect and mechanism of the mulberry leaf alkaloid, flavones, and polysaccharide intervention on diabetes, the overall metabolite profiling characteristics for the plasma of diabetic mouse was performed by using an ultra-performance liquid chromatography/electrospray-tandem mass spectrometry (UPLC-ESI-MS). The 8 potential biomarkers were found in diabetic mice plasma based on the data of MS/MS characteristics obtained from the UPLC-OrbitrapMS analysis, which mainly involved in sphingolipids, amino acid metabolic pathway. The principal component analysis showed that the normal group and model group were obviously distinguished and implied that metabolic disturbance was happened in diabetic mice plasma. The extracts of mulberry leaf flavonoids, polysaccharide, alkaloid had exhibited the effects of callback function for diabetic mice through regulating the amino acid metabolism and sphingolipid metabolism. PMID- 26552144 TI - [TRPV1 channel-mediated thermogenesis is a common mode for the Chinese pungent hot or pungent-warm herbs to demonstrate their natures]. AB - To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent hot (warm) herbs to demonstrate their natures. PMID- 26552145 TI - [Establishment of MDCK cell models expressing human MATE1 or co-expressing with human OCT1 or OCT2]. AB - To establish single- and double-transfected transgenic cells stably expressing hMATE1, hMATE1 cDNA was cloned by RT-PCR from human cryopreserved kidney tissue, and subcloned into pcDNA3.1(+) plasmid by virtue of both HindIII and Kpn I restriction enzyme sites. Subsequently, the recombined pcDNA3.1(+)- hMATE1 plasmid was transfected into MDCK, MDCK-hOCT1 or MDCK-hOCT2 cells using Lipofectamine 2000 Reagent. After a 14-day-cultivation with hygromycin B at the concentration of 400 ug . mL(-1), all clones were screened with DAPI and MPP+ as substrates to identify the best candidate. The mRNA content of hMATE1, the cellular accumulation of metformin with or without cimetidine as inhibitor, or transportation of cimetidine was further valuated. The results showed that all of the three cell models over expressed hMATE1 mRNA. The cellular accumulation of metformin in MDCK-hMATE1 was 17.6 folds of the control cell, which was significantly inhibited by 100 umol . L(-1) cimetidine. The transcellular transport parameter net efflux ratios of cimetidine across MDCK-hOCT1/hMATE1 and MDCK-hOCT2/hMATE1 monolayer were 17.5 and 3.65, respectively. In conclusion, cell models with good hMATE1 function have been established successfully, which can be applied to study the drug transport or drug-drug interaction involving hMATE1 alone or together with hOCT1/2 in vitro. PMID- 26552146 TI - [The interactions between natural products and OATP1B1]. AB - Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 umol . L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use. PMID- 26552147 TI - [The anti-tumor activity and molecular mechanisms of an Aurora kinase inhibitor ZLJ213 in suppressing colon cancer growth]. AB - The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg . kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 umol . L(-1) analyzed by ELISA. Under the concentration of 0.08 umol . L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer. PMID- 26552148 TI - [Synthesis and antioxidative activity of flavone derivatives containing 1,2,4 triazole structure]. AB - Using bioactive compounds 7-hydroxy flavone, salicylaldehyde, cinnamic acid and 4 amino-5- mercapto-1,2,4-triazoles as starting materials, three new types of flavone derivatives containing 1,2,4-triazole structure were synthesized via different step reactions. These new compounds were characterized by 1IHNMR, ESI MS, IR and elemental analysis. Their scavenging effects on the superoxide radical (O2.-), hydroxyl radical (.OH), DPPH . radical and their total reduction activities were tested. The results showed that all of the compounds possessed some antioxidative activity at the concentration of 0.5 mg . mL(-1), but the scavenging ability of the target compounds was lower than that of the standard compound Vc. PMID- 26552149 TI - [Design, synthesis and antiproliferative activities of artemisinin derivatives substituted by N-heterocycles]. AB - Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF 7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing. PMID- 26552150 TI - [The mechanism of action of valsartan studied by HPLC-TOF/MS]. AB - High performance liquid chromatography-time-off-flight mass spectrometer (HPLC TOFMS) technology coupled with partial least squares discriminant analysis (PLS DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs. PMID- 26552151 TI - [UPLC-Q-TOF/MS analysis of phospholipids metabolite profiling in plasma of type 2 diabetes mellitus rat]. AB - This study reported the analysis of plasma phospholipid metabolism of the rats and the pathological biomarkers between the type 2 diabetes model control group (MC) and the normal control group (NC). SD rats were randomly divided into 2 groups: NC and MC. To investigate state of plasma metabolite profiling in normal body, type 2 diabetes mellitus (T2DM) model group using UPLC-Q-TOF/MS which was used as analysis tool in this research. The compounds were identified by UPLC-Q TOF/MS based on MS/MS fragment ions information, element composition in MassLynx 4.1 and the Lipid Maps database. The sign of two groups of samples in specific markers for screening was through a software package in R software (BioMark software). The results show that the pathological markers were mainly phosphatidylcholine (PC) and triglycerides (TG); the 2-acyl PC in the MC group was less more obviously than that in the NC group; high carbon number and high degree of unsaturation of the TG was reduced under the condition of type 2 diabetes. In the state of type 2 diabetes, metabolic changes occurred in rat plasma phospholipids obviously, which had a close relationship with the occurrence and development of T2DM. PMID- 26552152 TI - [Simultaneous determination and quantitation of anthraquinones, lignans and flavonoids in Xiao-Cheng-Qi Tang, Hou-Po-San-Wu Tang and Hou-Po-Da-Huang Tang by HPLC]. AB - A simple and selective HPLC method for simultaneous determination and quantification of anthraquinones, lignans and flavonoids in Xiao-Cheng-Qi Tang (XCQT), Hou-Po-San-Wu Tang (HPSWT) and Hou-Po-Da-Huang Tang (HPDHT) was developed and validated. An Agilent Zorbax SB-C 18 (4.6 mm x 250 mm, 5 um) column with the mobile phase of acetonitrile and 0.5% acetic acid aqueous solution in gradient elution mode was used. The flow rate was 1.0 mL . min(-1) at 30 degrees C, and injection volume was 10 uL. The detection wavelength was set at 254 nm and 294 nm simultaneously for the quantitative analysis. The current HPLC assay was validated for linearity, intra-day and inter-day precisions, accuracy, recovery and stability. The method was applied to the content comparison of the gallic acid, cinnamic acid, sennoside A, sennoside B, rhein, emodin, aloe-emodin, chrysophanol, physcion, magnolol, honokiol, narirutin, naringin, hesperidin, neohesperidin, hesperetin, naringenin and nobiletin in XCQT, HPSWT and HPDHT. The good linear equations of eighteen constituents were obtained within the investigated ranges (r > 0.998). The recovery of the method was 94.28%-99.89% and the precision was less than 5%. The sample was stable within 16 h. There were some differences between the contents of anthraquinones, lignans and flavonoids in analogous formulae about XCQT. XCQT contained the greatest abundance of anthraquinones and flavonoid, HPSWT contained the greatest abundance lignans. In conclusion, the methods are simple, low-cost, precise, accurate and reliable for the determination of eighteen constituents in analogous formulae about XCQT, and these results provide methodological support for its quality control. PMID- 26552153 TI - [Mechanism of cellular uptake and transport mediated by integrin receptor targeting trimethyl chitosan nanoparticles]. AB - This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avbeta3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 +/- 4.2) nm and (259.5 +/- 3.3) nm. Electric potential of those two nanoparticles were (33.5 +/- 0.8) mV and (25.7 +/- 1.6) mV. Encapsulation efficiencies were (76.0 +/- 2.2) % and (74.4 +/- 2.0) %. Drug loading efficacies were (50.1 +/- 2.1) % and (26.1 +/- 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs. PMID- 26552154 TI - [Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system]. AB - A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 +/- 0.42) nm, and zeta potential of (7.6 +/- 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma. PMID- 26552155 TI - [Mechanism of genuineness of Glycyrrhiza uralensis based on SNP of beta-Amyrin synthase gene]. AB - beta-Amyrin synthase (beta-AS) genes of Glycyrrhiza uralensis from 6 different regions were analyzed by PCR-SSCP and sequenced, then the correlationship between beta-AS SNP and regions of Glycyrrhiza uralensis were determined. According to the 1 coding single nucleotide polymorphism on the first exon of beta-AS gene at 94 bp site, Glycyrrhiza uralensis could be divided into 3 genotypes. In these genotypes, the percentage of 94A type in genuine regions was much higher, and it had significant differences with the percentage in non-genuine regions (P < 0.001). The results of the experiment proved that different beta-AS genotypes at 94 bp site from different regions may be one of the important reasons to result in the genuineness of Glycyrrhiza uralensis. PMID- 26552156 TI - [The expression of BmK AngM1 in Mut(s) and Mut(+) recombinants of Pichia pastoris]. AB - BmK AngM1 is a long-chain scorpion toxin purified from the venom of Buthus martensii Karsch. It has been reported to exhibit evident analgesic effect and low toxicity, and has the potential to be a novel analgesic drug. The BmKAngM1 gene was transformed into Pichiapastoris GS115. Mut+ and Mut(s) recombinant strains were screened by phenotype and Mut+ recombinant strains were used to detect BmK AngMl gene copy number in the real-time PCR. Expression of BmK AngM1 in the Mut+ recombinant strain was compared with that of the Mut(s) recombinant strain with the same single copy of BmK AngM1 gene under the same condition. The results indicated that the transcription level of BmK AngM1 gene in the Mut(s) recombinant strain was 2.7 fold of that in the Mut recombinant strain in the real time PCR, and the expression of BmK AngM 1 in the Mut(s) recombinant strain was 1.5 fold of that in the Mut+ recombinant strain. Therefore, Mut(s) recombinant strain showed better ability to express BmK AngM1 than Mut+ recombinant strain. PMID- 26552157 TI - [Research advances on analysis of medicinal plants transcriptome]. AB - The transcriptome represents the whole complement of RNA transcripts in cells or tissues and reflects the expressed genes at various life stages, tissue types, physiological states, and environmental conditions. Transcriptomics study concerning medicinal plants has become the most active area in medicinal plant genome research. Transcriptome analysis provides a comprehensive understanding of gene expression and its regulation. The study of its transcriptome has great significance in solving the questions of genetic evolution, genetic breeding, ecology and so on. Here we report the application status of transcriptomics in medicinal plants based on emergence, development and methodology of transcriptomics. PMID- 26552158 TI - [Bioinformatics analysis and expressed level of histone methyltransferase genes in Lonicera japonica]. AB - Twenty-three histone methyltransferase genes were obtained from transcriptome dataset of Lonicera japonica. The nucleotide and proteins characteristics, subcellular localization, senior structural domains and conservative forecasting were analyzed. The result of phylogenetic tree showed that 23 histone methyltransferases were mainly divided into two groups: lysine methyltransferase and arginine methyltransferases. The result of gene expression showed that 23 histone methyltransferases showed preference in terms of interspecies and organs. They were more expressed in buds of L. japonica than in L. japonica var. chinensis and lower in leaves of L. japonica than in L. japonica var. chinensis. Eight genes were specific expressed in flower. These results provided basis for further understanding the function of histone methyltransferase and epigenetic regulation of active ingredients of L. japonica. PMID- 26552159 TI - [Data mining of simple sequence repeats in transcriptome sequences of Tibetan medicinal plant Zangyinchen Swertia mussotii]. AB - MISA (MicroSAtelite) software was employed to screen SSRs in 68 787 contigs of Swertia mussotii transcriptome sequences. 5 610 SSRs were distributed in 5 099 contigs which accounted for 7.41% of 68 787 contigs. There are 220 kinds of SSR motifs existing in S. mussotii transcriptome. On average, SSRs occurred every 12.60 kb in length. In the SSRs, the tri-nucleotide repeat motif was the most abundant (45.99%), followed by the di-nucleotide (41.62%). AT/TA and AAT/TTA were the main types of motif in di-, tri-nucleotide repeats. The repeat numbers of SSRs which from S. mussotii transcriptome SSRs were mainly from 5 to 10 and motif length of them mostly ranged from 12 bp to 30 bp. A total of 30 651 contigs were annotated, and only 1 447 SSRs were occurred in protein-coding regions. In the six repeat motifs, tri-nucleotide repeats were the most abundant in coding regions (928). There are abundant SSRs in S. mussotii transcriptome with high frequency and various types, indicating their usefulness in theory. This research may lay the foundation for designing the targeted SSR primers and developing SSR molecular markers by mining the information of SSRs loci in S. mussotii transcriptome sequences data. PMID- 26552160 TI - [Identification and bioinformatics analysis of genes associated with MVA pathway in Magnolia officinalis]. AB - Methyl valerate (MVA) pathway is one of the important ways for synthesis of terpenoids. This study was based on data of the transcriptome sequencing of Magnolia officinalis, the associated genes MoACOT, MoHMGS, MoHMGR, MoMK in methyl valerate (MVA) pathway, were completed in detail by using bioinformatics methods. The results of analysis showed that MoACOT and MoMK were stable hydrophobic proteins, MoHMGS and MoHMGR were unstable hydrophobic protein. The secondary structures of all proteins were hybrid architecture,and alpha helical were the major motifs. There were no clear transmembrane domains in MoACOT, MoHMGS and MoMK, but two transmembrane domains were founded in MoHMGR which were from 39-61 aa and 82-104 aa resepectively. The results of evolutionary relationship analysis showed that MoACOT, MoHMGS, MoHMGR and MoMK had relative close relationship to angiosperm or dicotyledonous plants, and accorded with genetic evolution rule. From transcriptome data, transcripted level of MoACOT, MoHMGS, MoHMGR, MoMK in M. officinalis and M. officinalis var. biloba was not significantly different. The result provided theoretical reference for study on Methyl valerate (MVA) pathway of terpenoid of M. officinalis. PMID- 26552161 TI - [Transcriptome profiling and analysis of Panax japonicus var. major]. AB - The rhizome of Panax japonicus var. major have been used as the natural medicinal agent by Chinese traditional doctors for more than thousand years. Most of the therapeutic effects of P. japonicus var. major had been reported due to the presence of tetracyclic or pentacyclic triterpene saponins. In this study, Illumina pair-end RNA-sequencing and de novo splicing were done in order to understand the pathway of triterpenoid saponins in this species. The valid reads data of 15. 6 Gb were obtained. The 62 240 unigenes were finally obtained by de novo splicing. After annotation, we discovered 19 unigenes involved in ginsenoside backbone biosynthesis. Additionally, 69 unigenes and 18 unigenes were predicted to have potential function of cytochrome P450 and UDP glycosyltransferase based on the annotation results, which may encode enzymes responsible for ginsenoside backbone modification. This study provides global expressed datas for P. japonicus var. major, which will contribute significantly to further genome-wide research and analysis for this species. PMID- 26552162 TI - [Cloning and expression analysis of GGPPS gene from Panax notoginseng]. AB - According to the transcriptome dataset of Panax notoginseng, the key geranylgeranyl pyrophosphate synthase gene (GGPPS) in terpenoid backbone biosynthesis was selected to be cloned. Using specific primer pairs combining with RACE (rapid amplification of cDNA ends) technique, the full-length cDNA sequence with 1 203 bp, which containing a 1 035 bp open reading frame, was cloned and named as PnGGPPS. The corresponding full-length DNA sequence contained 2 370 bp, consisted of 1 intron and 2 exons. The deduced protein PnGGPPS contained 344 amino acids and shared more than 73% identity with GGPPS from Ricinus communis and Salvia miltiorrhiza. PnGGPPS also had specific Aspartic acid enrichment regions and other conserved domains, which belonged to the Isoprenoid Biosyn-C1 superfamily. The quantitative real-time PCR showed that PnGGPPS expressed in different tissues of 1, 2, 3 years old root, stem, leaf and 3 years old flower, and the expression level in 3 years old leaf was significant higher than that in other organs, which suggested that it might not only be involved in the regulation of the growth and development, but also be associated with the biosynthesis of chlorophyll and carotenoids, the development of chloroplast, the shade habit and the quality formation of P. notoginseng. PMID- 26552163 TI - [Advances in chemical constituents and bioactivity of Salvia genus]. AB - The genus Salvia in the family Lamiaceae with nearly 1 000 species, is widespread in temperate and tropical regions around the world. Many species of genus Salvia are important medicinal plants with a long history of which Danshen (the dried roots and rhizomes of S. miltiorrhiza) is one of the most popular herbal traditional medicines in Asian countries. The chemical constituents from Salvia plants mainly contain sesquiterpenoids, diterpenoids, triterpenoids, steroids and polyphenols etc, which exhibit antibacterial, antidermatophytic, antioxidant, anti-inflammatory, antineoplastic, antiplatelet aggregation activities and so on. In this article, the development of new constituents and their biological activities of Salvia genus in the past five years were reviewed and summarized for its further development and utilization. PMID- 26552164 TI - [Comparison between Lysimachiae Herba and Desmodii Styracifolii Herba in pharmacological activities]. AB - Lysimachiae Herba and Desmodii Styracifolii Herba are common traditional Chinese medicines for treating lithiasis. Both of them have efficacies of clearing heat, diuresis and eliminating calculi. However, there are some differences in their clinic applications. The former is mainly used to treat hepatolithiasis, gallstones, jaundice, stranguria and gout; Whereas the latter is mainly used to treat urinary calculus. In this paper, the pharmacological effects of Lysimachiae Herba and Desmodii Styracifolii Herba on removing calculus, choleresis, anti inflammation and oxidation resistance were compared and analyzed based on document retrieval. In conclusion, both of them show the preventive and therapeutic effects on kidney stones and gallstones. Particularly, Desmodii Styracifolii Herba has a better effect in treating the kidney stones, while Lysimachiae Herba has a better effect in treating cholesterol gallstones. PMID- 26552165 TI - [Graded ethanol precipitation method on physicochemical properties and antioxidant activities of polysaccharides extracted from Astragalus Radix]. AB - Astragalus polysaccharide has been widely used in food and medicinal industry owing to its health-promoting properties. In order to characterize better the relationship among molecular weight, structure-activity and activities, a simple method was used different concentration of ethanol including 30% (PW30), 50% (PW50), 70% (PW70), 75% (PW75), 80% (PW80) and 90% (PW90) to precipitate Astragalus polysaccharides into different molecular weight. As a result, PW90 showed smooth surface and the strongest antioxidant activity among these six fractions (P < 0.05). In conclusion, graded ethanol precipitation was a simple method to separate Astragalus polysaccharides into different molecular weight with different antioxidant activity fractions. PMID- 26552166 TI - [Weibull distribution for modeling drying of Angelicae Sinensis Radix and its application in moisture dynamics]. AB - To establish the water dynamics model for drying process of Angelicae Sinensis Radix, the Weibull distribution model was applied to study the moisture ratio variation curves, and compared the drying rate and drying activation energy with the drying methods of temperature controllable air drying, infrared drying under different temperatures (50, 60, 70 degrees C). The Weibull distribution model could well describe the drying curves, for the moisture ratio vs. drying time profiled of the model showed high correlation (R2 = 0. 994-0. 999). The result proved that the drying process of Angelicae Sinensis Radix belonged to falling rate drying period. For the drying process, the scale parameter (a) was related to the drying temperature, and decreased as the temperature increases. The shape parameter (beta) for the same drying method, drying temperature had little impact on the shape parameter. The moisture diffusion coefficient increase along with temperature increasing from 0.425 x 10(-9) m2 x s(-1) to 2.260 x 10(-9) m2 x s( 1). The activation energy for moisture diffusion was 68.82, 29.60 kJ x mol(-1) by temperature controllable air drying and infrared drying, respectively. Therefore, the Weibull distribution model can be used to predict the moisture removal of Angelicae Sinensis Radix in the drying process, which is great significance for the drying process of prediction, control and process optimization. The results provide the technical basis for the use of modern drying technology for industrial drying of Angelicae Sinensis Radix. PMID- 26552167 TI - [Application of microwave technology in extraction process of Guizhi Fuling capsule]. AB - In this paper, optimization of the conditions of microwave technique in extraction process of Guizhi Fuling capsule in the condition of a pilot scale was carried out. First of all, through the single factor experiment investigation of various factors, the overall impact tendency and range of each factor were determined. Secondly, L9 (3(4)) orthogonal test optimization was used, and the contents of gallic acid in liquid, paeoniflorin, benzoic acid, cinnamic acid, benzoyl paeoniflorin, amygdalin of the liquid medicine were detected. The extraction rate and comprehensive evaluation were calculated with the extraction effect, as the judgment basis. Theoptimum extraction process of Guizhi Fuling capsule by microwave technology was as follows: the ratio of liquid to solid was 6: 1 added to drinking water, the microwave power was 6 kW, extraction time was 20 min for 3 times. The process of the three batch of amplification through verification, the results are stable, and compared with conventional water extraction has the advantages of energy saving, time saving, high efficiency advantages. The above results show the optimum extracting technology of high efficiency, stable and feasible. PMID- 26552168 TI - [Optimization of method for determination of Salviae Miltiorrhizae Radix et Rhizoma]. AB - OBJECTIVE: To optimize the method in the Chinese Pharmacopoeia for determining Salviae Miltiorrhizae Radix et Rhizoma. METHOD: Tanshinone II(A) and salvianolic acid B were selected as the index in optimization of the sample preparation method of Salviae Miltiorrhizae Radix et Rhizoma in Chinese Pharmacopoeia. Orthogonal test was used to optimize the extraction process of Salviae Miltiorrhizae Radix et Rhizoma, and concentration of contents were detected by high performance liquid chromatography method. A detection of using methanol water (85: 15) at wavelength of 270 nm was employed for tanshinone II(A) and a detection of using methanol-acetonitrile-formic acid-water (30:10:1: 59) at wavelength of 286 nm was employed for salvianolic acid B. RESULT: The optimized extraction process of tanshinone II(A) and salvianolic acid B was: extracted by 90% methanol and reflux twice (0.5 h each time) at 75 degrees C, extracted by 70% methanol and reflux twice (1.5 h each time) at 75 degrees C, respectively. CONCLUSION: Optimized extraction and determination methods could be used to reflect the content of tanshinone II(A) and salvianolic acid B in Salviae Miltiorrhizae Radix et Rhizoma more accurately and efficiently. PMID- 26552169 TI - [A new bisabolane-type sesquiterpenoid from Coreopsis tinctoria]. AB - To study the chemical constituents of the inflorescences of Coreopsis tinctoria from Xinjiang, isolation and purification of constituents were carried out by column chromatography on macroporous resin (D101) , MCI gel, MDS gel, silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures of the compounds were identified by physicchemical properties and spectral data analysis. Fourteen compounds were isolated and identified as coretinterpenoid A (1), coretinphenol (2), quercetin (3), quercetin-3-O-beta-glucopyranoside (4), luteolin (5), taxifolin (6), 7, 3', 5'-trihydroxyflavanone (7), isookanin (8), isookanin-7-O beta-D-glucopyranoside (9), 5, 7, 3', 5'-tetrahydroxyflavanone-7-O-beta-D glucopyranoside (10), butein (11), okanin (12), sulfuretin (13), and linocinnamarin (14). Compound 1 was a new isabolane-type sesquiterpenoid and compounds 4, 10 and 13 were isolated from this plant for the first time. PMID- 26552170 TI - [Studies on chemical constituents from Psychotria straminea]. AB - The chemical consituents from Psychotria straminea were separated and purified by column chromatographies on silica gel, Sephadex LH-20, ODS and RP-HPLC. The strictures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis, as well as comparisons with the data in literature. Sixteen compounds were isolated and elucidated as tectochrysin (1), apigenin (2), kaempferol (3), luteolin (4), diosmetin (5), quercetin (6), kaempferol-4'-O-methylether (7), rhamnetin (8), 7-hydroxycoumarin (9), 7-methoxycoumarin (10), scopoletin (11), lupeol (12), 30-oxo-lupeol (13), lupenyl acetate (14), alpha-amyrin (15), and ursolic acid (16). This is the first study on the chemical composition of P. Straminea, and all compounds were isolated from P. straminea for the first time. In addition to compounds 6 and 9, the other compounds were isolated from the genus Psychotria for the first time. PMID- 26552171 TI - [Chemical investigation of triterpenoids from Dichrocephala benthamii]. AB - The triterpenoids of Dichrocephala benthamii were investigated by means of silica gel, Sephadex LH-20 and semi-preparative HPLC. Nine triterpenoids were isolated from D. benthamii. By analysis of the EI-MS, NMR spectra and comparison to the data reported in literatures, the structures of these compounds were determined as beta-amyrin formiate (1), beta-amyrin acetate (2), beta-amyrenol (3), beta amyrone (4), 3beta-hydroxy-olean-11, 13 (18)-diene (5) , Delta12-oleanene (6) , friedelin (7), dammaradienyl acetate (8), epi-friedeband (9), respectively. Compounds 1-8 were isolated for the first time form this genus, compound 9 was isolated for the first time from this plant, whereas beta-amyrin formiate (1) was a new natural product. PMID- 26552172 TI - [Chemical constituents from lipophilic parts in roots of Angelica dahurica var. formosana cv. Chuanbaizhi]. AB - The chemical constituents from lipophilic parts in the roots of Angelica dahurica var. formosana cv. Chuanbaizhi were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods on silica gel and HPLC, and the chemical structures of compounds were determined by spectral data analyses. Twenty-nine compounds were obtained and identified as isoimperatorin (1), beta-sitosterol (2), imperatorin (3), bergapten (4), osthenol (5), xanthotoxin (6), isoimpinellin (7), dehydrogeijerin (8), phellopterin (9), isodemethylfuropinarine (10), 7-demethylsuberosin (11), alloimperatorin (12), xanthotoxol (13), isooxypeucedanin (14), alloisoimperatorin (15), demethylfuropinarine (16), 5-hydroxy-8-methoxypsoralen (17), oxypeucedanin methanolate (18), pabulenol (19), byakangelicin (20), marmesin (21), (+) decursinol (22), heraclenol (23), oxypeucedanin hydrate (24), marmesinin (25), ulopterol (26), erythro-guaiacylglycerol-beta-ferulic acid ether (27), threo guaiacylglycerol-beta-ferulic acid ether (28), and uracil (29). Compounds 5, 8, 11, 18, 21-23, and 26-28 were obtained from the roots of title plant for the first time. PMID- 26552173 TI - [Determine resource chemical component in ginkgo pollen simultaneously by UPLC-TQ MS]. AB - The present study is to determine the flavonoid glycosides, terpene lactones, biflavones, gingko acid and procyanidins of ginkgo pollen. UPLC-TQ-MS technology was used for the determination of 24 kinds of resource chemical composition in ginkgo pollen qualitatively and quantitatively. The results shows that the contents of rutin, quercetion 3-O-[4-O-(alpha-L-rhamnosyl )-beta-D-glucoside] and kaempferolis were 120.9, 114.0, 222.1 MUg x g(-1). In this paper, the contents of 24 kinds of chemical components of ginkgo pollen were determinated by UPLC-TQ-MS for the first time. This method is simple and quick, which will be benefit for recycling utilization of ginkgo pollen. PMID- 26552174 TI - [Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism]. AB - OBJECTIVE: To study the effect of aqueous extracts of Polygonum multiflorum (AEPM) on bile acid synthesis, metabolism and transfer-related molecules in rat liver and the hepatotoxicity-related mechanism of P. multiflorum. METHOD: Sprague Dawley rats were orally administered with 30, 60 g x kg(-1) APEM once everyday for consecutively 28 days. At the end of the experiment, mRNA and protein expressions of hepatic MRP3, MRP2, BSEP, FXR and CYP7A1 were detected by Real time PCR and Western blot RESULT: Compared with the normal group, the AEPM high dose group showed significant increases in mRNA expressions of hepatic MRP3 and BSEP of male rats (P < 0.05); AEPM high and low dose groups revealed a notable decrease in mRNA expressions of hepatic FXR (P < 0.05) and remarkable rises in mRNA expressions of hepatic MRP3, MRP2, BSEP, CYP7A1 among female rats (P < 0.05). According to the test results of western blot assay, AEPM high and low dose groups showed consistent changes in protein and mRNA expressions hepatic MRP3, MRP2, BSEP, FXR, CYP7A1. CONCLUSION: The 28 oral administration with AEPM in rats showed a certain effect on expressions of bile acid synthesis, metabolism and transfer-related proteins, as well as cholestatic or choleretic effects in the mRNA expression. PMID- 26552175 TI - [OMT inhibited TGF-beta1-induced cardiac fibroblast proliferation via down regulating p38MAPK phosphorylation in vitro]. AB - OBJECTIVE: To investigate the inhibitory effects of OMT on TGF-beta1-induced CFBs proliferation, and then explore the mechanism. METHOD: The experiment was randomly divided into 6 groups as following: control group (serum free DMEM), model group (20 MUg x L(-1) TGF-beta1), OMT low dose group (1.89 x 10(-4) mol x L(-1) + 20 MUg x L(-1) TGF-beta1), OMT medium dose group (3.78 x 10(-4) mol x L( 1) + 20 MUg x L(-1) TGF-beta1), OMT high dose group (7.56 x 10(-4) mol x L(-1) + 20 MUg x L(-1) TGF-beta1), SB203580 group (p38MAPK blocking agent, 1 x 10(-5) mol x L(-1) + 20 MUg x L(-1) TGF-beta1). Vimentin of CFBs was identified by immunocytochemical methods, alpha-SMA of myFBs as well. Inhibitory effects of OMT on CFBs proliferation was detected by the MTT assay. Picric acid Sirius red staining was analyzed collagen type I and collagen type III deposition. Western blot was determined the expression of p38MAPK, p-p38MAPK, collagen type I and collagen type III. RESULT: MTT results showed that OMT significantly inhibited CFBs proliferation induced by TGF-beta1 (P < 0.01) alpha-SMA immunocytochemical experiments suggested that OMT could protect against the CFBs proliferation. OMT could significantly decrease the deposition of collagen type I and collagen type III by Western bloting and picric acid Sirius red staining. Western blot results showed that TGF-beta1 enhanced p38MAPK phosphorylation, however OMT attenuated the phosphorylation of p38MAPK induced by TGF-beta1 (P < 0.01). CONCLUSION: OMT can inhibit the CFBs proliferation induced by TGF-beta1, and its mechanism may be involved in inhibiting p38MAPK phosphorylation. PMID- 26552177 TI - [Effects of Kaixin San formulas on behavioristics and central monoamine neurotransmitters of chronic stress rats]. AB - The efficacy of Chinese herbal formula in treating depression has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on central monoamine neurotransmitters of chronic stress rats and against depression based on their different components in plasma, in order to discuss the efficacy-comparability relationship and the possible efficacy mechanism. The classic isolation method and the chronic unpredictable mild stress (CUMS) depression model were combined to investigate the changes in contents in hippocampus and monoamine neurotransmitters (NE, DA, 5-HT) and the components of some formulas in plasma with HPLC and UPLC-Q-TOF-MSE methods. As a result, Dingzhi Xiaowan recorded in Essential Recipes for Emergent Use Worth A Thousand significantly increased the behavioral scores, NE and 5-HT contents in hippocampus and NE, DA and 5-HT contents in cortex, with the best anti-depressant effect. Dingzhi Xiaowan recorded in Complete Records of Ancient and Modern Medical Works showed a notable increase in sucrose preference and open field score in model rats, NE content in hippocampus and NE, DA and 5-HT contents in cortex, with a certain anti anti-depressant effect. Kaixin San recorded in Ishinpo showed remarkable rise in weight of model rats. NE content in hippocampus and DA content in cortex. Puxin Decoction recorded in A Supplement to Recipes Worth A Thousand Gold showed 5-HT content in hippocampus and DA content in cortex. Kaixin San recorded in Yimenfang only showed DA content in cortex. Kaixin Wan recorded in Essential Recipes for Emergent Use Worth A Thousand did not mention the antidepressant effect. According to the results, the formulas' different anti-depressant effects may be related to the different plasma components. PMID- 26552176 TI - [Effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction on myocardial apoptosis and relevant protein expressions in miniature swine phlegm and blood stasis type coronary heart disease model]. AB - There have been very few studies on the effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in inhibiting apoptosis in myocardial ischemial injury caused by coronary heart disease. In this experiment, Gualou Xiebai Banxia decoction combined with-Xuefu Zhuyu decoction were used to intervene the miniature swine phlegm and blood stasis type coronary heart disease model, in order to observe the effect of the combined prescription on the myocardial apoptosis and the expressions of Bcl-2, Bax, Caspase-3, Caspase-9 in the model. Totally 15 Chinese experimental miniature swine were adopted and randomly divided into the control group, the model group and the phlegm and stasis-treating group. The model group and the stasis-treating group were fed with high fat diets for two weeks, intervened with the coronary artery injury and then given drugs and high fat diets for eight weeks. The control group was fed with ordinary diets for 10 weeks, without the coronary artery injury. After the experiment, myocardia at the juncture of infracted areas were collected and made into formalin-fixed paraffin sections. The TDT-mediate dUTP nick end labeling (TUNEL) assay was used to detect the myocardial apoptosis. The immunohistochemistry (IHC) technique was applied to detect Bcl-2, Bax, Caspase-3, Caspase-9 levels in myocardial tissues. According to the findings, the apoptosis indexes (AI) for the control group, the model group and the phlegm and stasis treating group were 0.92%, 27.68%, 17.28%, respectively. The AI of the phlegm and stasis-treating group was significantly lower than that of the model group (P < 0.01). Compared with the model group, the phlegm and stasis-treating group showed significantly higher Bcl-2 protein expression (P < 0.01) and lower Bax, Caspase-3 and Caspase-9 protein expressions (P < 0.01). In conclusion, Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction have a significant protective effect against the myocardial apoptosis in miniature swine phlegm and blood stasis type coronary heart disease model. PMID- 26552178 TI - [Study on effect of tetramethylpyrazine on proliferation and apoptosis of leukemic U937 cells and its mechanism]. AB - OBJECTIVE: To study the proliferation and apoptosis of tetramethylpyrazine (TMP) on leukemic U937 cells and its possible mechanism. METHOD: The inhibitory effect of TMP on the proliferation of U937 cells was detected by CCK-8 assay. The cell apoptosis and cycle distribution were examined by the flow cytometry. The mRNA expressions of bcl-2 and P27 were determined by the Real-time PCR. Western blot was carried out to detect bcl-2, caspase-3, cyclin E1, CDK2 and P27 expressions. RESULT: TMP inhibited the proliferation of U937 cells in a dose-and-time dependent manner, with IC50 value of 160 mg x L(-1) at 48 h. In addition, TMP could induce the apoptosis of U937 cells and block the cell cycle in G0/G1 phase. According to the results of Real-time PCR and Western blot, TMP could down regulate the expression of apoptosis-related molecule bcl-2, cycle-related protein cyclin E1 and CDK2 and up-regulate caspase-3 and P27. CONCLUSION: TMP shows the effects in inhibiting the proliferation of leukemic U937 cells and inducing the apoptosis. Its mechanism may be related to the impacts on the cell cycle distribution, down-regulation of the bcl-2 expression, which finally activates caspase-3, starts the apoptosis path and causes the cell apoptosis. PMID- 26552179 TI - [Effect of Ligusticum wallichii-containing serum on expressions of Toll-like receptor 4 and myeloid differentiation factor 88 in hepatic stellate cells]. AB - To observe the effect of Ligusticum wallichii-containing serum on the expressions of Toll-like receptor 4 and myeloid differentiation factor 88 in hepatic stellate cells. Clean-grade SD rats were randomly divided into 5 groups and orally given L. wallichii decoction, colchicine and normal saline for 7 d to prepare L. wallichii-containing serums. Except for the blank group, all of the remaining groups were stimulated with LPS 1 mg x L(-1) for 24 h. After being intervened, the L. wallichii-containing serums were cultured in 5% CO2 incubator at 37 degrees C for 24 hours. The expression of TLR4 and MyD88 were detected by RT-PCR and Western blot. After HSC was stimulated with LPS, TLR4 and MyD88 mRNA and protein expressions were significantly higher than the blank control group (P < 0.01). After being intervened with L. wallichii-containing serum, TLR4 and MyD88 mRNA and protein expressions were notably lower than the model group (P < 0.05 or P < 0.01). In conclusion, L. wallichii-containing serum could regulate the TLR4 signaling pathway and show the anti-fibrosis effect by inhibiting the expression of TLR4 and MyD88 in LPS-induced HSCs. PMID- 26552180 TI - [Study on material base of Ligusticum wallichii for treating brain ischemia and its molecular mechanism based on molecular docking]. AB - To explore the effective ingredients and mechanism of Ligusticum wallichii in treating brain ischemia. Four brain ischemia-related target proteins were selected in the joint screening for the 45 component in L. wallichii reported in literatures based on molecular docking by reference to the corresponding drugs in the market. According to the docking results, multiple components in L. wallichii, such as phthalides, were superior to the corresponding drugs in the market, suggesting that they may be the major effective components in L. wallichii for treating brain ischemia. The method can be used to study the material base and molecular mechanism of traditional Chinese medicines. PMID- 26552181 TI - [Numerical analysis on network characteristics of communities in herb-pairs network]. AB - To interpret the traditional Chinese medicine (TCM) theory by the network technology, in order to promote the modernization and programming of studies on compatibility of TCMs. In this paper, efforts were made to express the direct interactions between drugs through the herb-pair network, analyze the community characteristics of the network and its relations with blood-Qi theory, and study the expression of blood-Qi theory on the herb-pair network through prescriptions. According to the findings, the herb-pairs network showed a strong community structure characteristics; Each community is composed of a series of herb pairs with close correlations, and either blood efficacy or Qi efficacy but not both of them. Based on that, the 386 single TCM ingredients involved by the herb-pair network were divided into three types of communities: Blood (B) community, Qi (Q) community and uncertain community. According to the statistical results of 262 prescriptions mapped onto the three types of communities, if a prescription contains single herbs of the Q community, the probability that it contains single herbs o the B community is 99.84%; Meanwhile, there are 140 prescriptions containing single herbs of both the Q community and the B community. The result is completely coincident with the TCM Blood-Qi theory that single herbs belong to both Q and B communities or the B community, because Qi regulation leads to blood regulation, but not vice versa. For example, a patient with hemorrhage due to trauma or blood-heat, Qi tonifying prescriptions may aggravate hemorrhage. In this paper, authors found high-recognition macroscopic network numerical characteristics to network data reference for judging rationality of new prescriptions, and proved human blood and Qi relations from the perspective of data analysis. PMID- 26552182 TI - [Effect of Guizhi Fuling capsule and combination of active ingredients on rats with uterine myoma]. AB - It is to observe the therapeutic action of Guizhi Fuling capsule and the combination of active ingredients on model rats with uterine leiomyoma. The hysteromyoma rats models was established in rats by loading eatrogen, to observe the effect on pathological condition of uterus, uterus wet weight, the content of estradiol and progesterone. Guizhi Fuling capsule and the combination of active ingredients remarkably decreased uterus weight, restrained the excess proliferation of the smooth muscle of uterus, decreased the estraiol and progesterone in blood serum. Guizhi Fuling capsule and the combination of active ingredients can restrain the formation of hysteromyoma in a dose-dependent manner. Perhaps the combination of active ingredients is the material foundation of antihysteromyoma. PMID- 26552183 TI - [Study on effect of total matrines and extracts from Periplaneta americana on negative endometrial cancer cell JEC of progesterone receptors]. AB - To study the effect of total matrines and extracts from Periplaneta americana on negative endometrial cancer cell JEC of progesterone receptors. After detecting the effect of total matrine, extracts from P. americana and their combination on JEC cells' growth inhibition, cell cycle, P53 and c-erbB-2 gene protein expressions through MTT, flow cytometry instrument and Western blot method, the author found that, (1) MTT: total matrines and extracts from P. americana could inhibit the growth of JEC cell, with significant increase in the inhibitory effect in the combination group. (2) Flow cytometry instrument: the cell cycle at G0/G1 increased after the treatment with total matrines, the cell cycle at G2/M increased after the treatment with extracts from periplaneta americana, and the ratio of G0/G1 cell cycle in the combination group was significantly higher than the other groups, with inhibition in cell growth and statistical difference in inter-group comparison (P < 0.05). (3) Western blot: the expression level of P53 increased and c-erbB-2 decreased after the treatment with total matrines, extracts from P. americana and their combination on JEC cell, with statistical difference in inter-group comparison (P < 0.05). The above results suggested that total matrines, extracts from P. americana and their combination could induce cell cycle arrest and inhibit the growth of JEC cell by up-regulating P53 and down-regulating the c-erbB-2 level. PMID- 26552184 TI - [Identification of the metabolites of Dingzhi Xiaowan extract in depressive rat plasma, urine, feces and bile after intragastric administration]. AB - Dingzhi Xiaowan is a widely used traditional Chinese medicine in treating depression, which is a similar formula of Kaixinsan. In this research, a rapid ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method was established to analyze the metabolites of Dingzhi Xiaowan in depressive model rat plasma, bile, urine and feces. After we established Chronic unpredictable mild stress (CUMS) model rats and orally administrated Dingzhi Xiaowan, rat plasma, bile, urine and feces samples were collected and prepared. Using Waters Cortects UPLC C18 column (2.1 mm x 50 mm, 1.6 MUm), acetonitrile-0.1% formic acid mobile phase gradient, these samples were analyzed and 33 metabolites of nine bioactive compounds were detected and tentatively identified by Metabolynx. Among the 33 metabolites, three metabolites were identified from plasma sample, three came from bile sample, and 27 metabolites were identified from urine and feces samples. This approach provided a rapid method for characterizing the metabolites of Dingzhi Xiaowan and gave the truly active structures and the action mechanism of their antidepressant effects. PMID- 26552185 TI - [Toxicokinetics of bakuchiol, hepatic and renal toxicity in rats after single oral administration of Psoraleae Fructus and combination with Glycyrrhizae Radix et Rhizoma]. AB - To study the toxicokinetics of bakuchiol, hepatic and renal toxicity in rats after single oral administration of Psoraleae Fructus and combined with Glycyrrhizae Radix et Rhizoma, in order to provide scientific evidences for clinical safe medication use. A total of 35 SD rats were randomly divided into seven groups: vehicle (distilled water) control group, Glycyrrhizae Radix et Rhizoma group, positive control (aristolochic acid A) group, Psoraleae Fructus (40 g x kg(-1)) group( both male and female rats), Psoraleae Fructus and Glycyrrhizae Radix et Rhizoma (40 +20) g x kg(-1) group (both male and female rats). HPLC-UV method was used to determine the concentration of bakuchiol in rat plasma at different time points after single oral administration. Plasma alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), plasma creatinine (Cr), N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (Kim-1) were measured after administration for 24 h. The main toxicokinetics parameters of bakuchiol in rats exert significantly gender difference. When Psoraleae Fructus combination with Glycyrrhizae Radix et Rhizoma, the total area under the plasma concentration-time curve( AUC), C(max), and plasma clearance (CL) of bakuchiol were increased, respectively; CL, half life (t1/2) were decreased, and T(max) were prolonged. The biochemical indicators (including ALT, AST, BUN, Cr and KIM-1 level) in different dose of Psoraleae Fructus groups, were found no statistically significant difference when compared with vehicle control group. The level of NAG in both Psoraleae Fructus and compatibility with Glycyrrhizae Radix et Rhizoma groups were significant increased (P < 0.05). There are obvious effects on toxicokinetics of bakuchiol in rats when Psoraleae Fructus combined with Glycyrrhizae Radix et Rhizoma. Renal toxicity induced by Psoraleae Fructus at high dose was observed after single oral administration and no liver damage in rats was found. PMID- 26552186 TI - [Mining analysis and experience summary for chronic atrophic gastritis cases treated by Professor LIU Feng-bin]. AB - To summarize Professor LIU Feng-bin's clinical experience and theoretical thoughts on chronic atrophic gastritis (CAG), the study group designed a retrospective study on his case series and expert interview. First of all, the data of CAG patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine between 2009 and 2013, e. g. herbs, diseases, syndrome type, prescription amount and number of herbs, was collected and processed. The statistical description and binary logistic regression were used to determined the syndrome type, initial basic remedy and modification. During the statistics, a complete and sub-group analysis was performed simultaneously. After the expert interview, the syndrome type and medication were finalized. As a result, a total of 228 CAG patients aged at (50.30 +/- 10.18) were collected, including 151 males (66.23%). Of them, the TCM diagnosis and syndrome type were extracted from the information of 157 patients, including 115 cases with gastric stuffiness, 23 cases with gastric pain, 19 missing cases, 2 cases with spleen stomach weakness syndrome, 57 cases with spleen deficiency and dampness-heat syndrome, 18 cases with spleen-stomach disharmony syndrome, 23 cases with syndrome of liver depression syndrome, 21 cases with liver qi invading stomach syndrome and 26 qi and yin deficiency syndrome, respectively. All of the 228 patients used totally 104 herbs, while the subgroups with 157 patients used 94 herbs. The most frequently used 15 herbs used in each groups were analyzed to determine the initial basic remedy and modification. Subsequently, based on the information of the sub-groups with 157 patients, with the syndrome type as the dependent variable, the logistic regression analysis was made on the most frequently used 32 herbs, in order to determined the modification in herbs for different syndrome types. After experts reviewed and modified, they believed the main causes of CAG were dietary irregularities, moodiness and weak constitution; the pathogenesis of CAG was spleen deficiency with qi stagnation, heat depression and blood stasis in the stomach meridian. The above six syndrome types and 12 herbs were determined, including Pseudostellariae Radix, Poria, Atractylodismacrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Fritillariae Thunbergii Bulbus, Sepiae Endoconcha, Arecae Pericarpium, Aurantii Fructus, Perillae Caulis, Herba Hedyotis Diffusae, Scutellariae Barbatae Herba, Curcumae Rhizoma. This study summarized Professor LIU Feng-bin's clinical experience and theoretical thoughts of chronic atrophic gastritis based on clinical practice data and expert interview, with a rigorous design and good scientificity and practicability. PMID- 26552187 TI - [Clinical study on Yihong Kangnaoshuan capsule in treating lacunar infarction pure motor hemiparesis]. AB - With the treatment of lacunar cerebral infarction with pure motor hemiparesis (PMH) attach importance to the treatment effect, application benefit of Yihong Kangnaoshuan capsule in the treatment of further effect. Treatment of PMH is mainly depending on the thorough discussion on the cause, to determine the clinical value of treatment based on the principle of. Through the research of Zhejiang People's Hospital of Fenghua from 2013 March to 2014 September 178 cases of pure motor hemiparesis were the benefit of Yihong Kangnaoshuan capsule and vedrin capsule treatment, compared the indexes of efficacy after treatment and blood rheology. Finally found the benefits of Yihong Kangnaoshuan capsule in the application process with high safety, efficacy and greater proportion. And in favor of blood lipid and blood rheology indicators of stability, the repair of neurological function is more. Therefore, clinicians should be applied benefit of red brain thrombus capsule in the treatment of PMH. But the overall difference between drugs is need to further comparison, in order to ensure clinical curative effect. PMID- 26552188 TI - [Rapid multi-elemental analysis on four precious Tibetan medicines based on LIBS technique]. AB - The laser-induced breakdown spectroscopy (LIBS) was applied to perform a qualitative elementary analysis on four precious Tibetan medicines, i. e. Renqing Mangjue, Renqing Changjue, 25-herb coral pills and 25-herb pearl pills. The specific spectra of the four Tibetan medicines were established. In the experiment, Nd: YAG and 1 064 nm-baseband pulse laser were adopted to collect the spectra. A laser beam focused on the surface of the samples to generate plasma. Its spectral signal was detected by using spectrograph. Based on the National Institute of Standard and Technology (NIST) database, LIBS spectral lines were indentified. The four Tibetan medicines mainly included Ca, Na, K, Mg and other elements and C-N molecular band. Specifically, Fe was detected in Renqing Changjue and 25-herb pearl pills; heavy mental elements Hg and Cu were shown in Renqing Mangjue and Renqing Changjue; Ag was found in Renqing Changjue. The results demonstrated that LIBS is a reliable and rapid multi-element analysis on the four Tibetan medicines. With Real-time, rapid and nondestructive advantages, LIBS has a wide application prospect in the element analysis on ethnic medicines. PMID- 26552189 TI - [Morphological and TLC identification on Tibetan medicine Asteris Flos]. AB - Tibetan medicine Asteris Flos is the flowers of Aster souliei, A. flaccidus, and A. asteroides, with the function of clearing away heat and toxic matter, relieving cough, and removing phlegm. In order to control the quality of Asteris Flos, the morphological and chemical methods were established for identification of three origins. The morphological features of three species were described and photographed, and the microscopic characteristics of three drug powders were also described in detail and pictured. The results showed that three origins of Asteris Flos could be easily distinguished by their macro- and micro-morphologic features, and a key for distinguishing the three origins was given. Moreover, a TLC method, with apigenin-7-O-beta-D-glucurono pyranoside and chlorogenic acid as chemical references, was also established for the identification of three origins. The results showed that the TLC chromatograms of the flowers of A. souliei and A. flaccidus were very similar, but different from that of A. asteroides. The established macroscopic, powder microscopic and TLC methods for identification of three origins of AF were simple, accurate, and reproducible, and also effective and easy to operate. PMID- 26552190 TI - [Discussion about risk and management of Chinese patent medicine with double identity]. AB - Chinese patent medicine with double identity was a special phenomenon, and many preparations not only were prescription drugs but also over the counter ( OTC) drugs, which brought a lot of trouble. Based on statistics of list of OTC medicines of CFDA, related varieties, route of administration and functions of these drugs were searched. The causes of insufficient were analyzed and the potential risk was investigated. To ensure the safety of drug usage for the patient, risk management system should be set up by improving the technical requirements for registration, improving the drug labels and manuals, playing the role of pharmacists in pharmacy services and raising awareness of doctor and patient for these drugs. PMID- 26552191 TI - [Evolution, characteristics and enlightenment of self-innovation of traditional Chinese medicine industry]. AB - Traditional Chinese medicine industry is China's strategic emerging industry with great potential for self-innovation. Traditional Chinese medicine industry has successively experienced four stages which are the foundation (laying stage), the core status (establishing stage), the modern system (exploring stage), and the modernization system (constructing stage). Throughout the evolution of the self innovation in traditional Chinese medicine industry, it presents distinct characteristics which we can explore the beneficial enlightenment. PMID- 26552192 TI - [Efficacy analysis and theoretical study on Chinese herbal properties of Acai (Euterpe oleracea)]. AB - Acai (Euterpe oleracea) emerged as a source of herb has a long history in South America, which was approved by the Ministry of Health used in China and it has been introduced planting in Guangdong and Taiwan. This article summarized applied history of Acai and its present status in China. Did theoretical study on the Chinese herbal properties of Acai based on the Chinese traditional philosophical culture to analysis the function and symptom preliminary, combining with used for medical recordation, chemical component, biological activity. It is aiming at establishing the theoretical foundation for the application under the guidance of TCM theory. PMID- 26552193 TI - The challenges of end of life care in acute hospitals. PMID- 26552194 TI - Issues post-stroke for Muslim people in maintaining the practice of salat (prayer): A qualitative study. AB - BACKGROUND: Muslims throughout the world perform salat (prayer) five times a day; salat involves a person reciting the Holy Qur'an while being in several positions. There are several steps that should be carried out before prayer, including wudhu (ablution) and covering one's awrah (body). OBJECTIVES: To identify educational needs for stroke patients and their caregivers in Malaysia. Another purpose is to report on the needs identified by stroke patients and their families related to salat. METHODS: Descriptive qualitative study. Phase 1 involved semi-structured interviews with stroke patients (n = 5), family caregivers (n = 5) and health professionals (n = 12) in Kelantan Malaysia. Phase 2 involved presenting the findings from Phase 1 to the health professionals with the aim of establishing priorities and processes to develop education strategies for stroke patients and their families. RESULTS: Preparing for and performing salat was challenging for both patient and family carers to do following a stroke. Themes identified were prayer and the meaning of the stroke events for participants, difficulties praying post-stroke, prayer as part of rehabilitation therapy. CONCLUSION: Providing culturally safe care should include how nurses assess and support patients and their caregivers post stroke to meet their prayer needs. Nurses have a role in discussing with stroke patients and their families how in addition to its spiritual and customary benefits, prayer and for Muslims reciting the Holy Qur'an can have cognitive and rehabilitation benefits, as well as being a source of psychological support for stroke patients. PMID- 26552195 TI - The investigation of factors that influence self-care agency and daily life activities among the elderly in the northern region of Turkey. AB - BACKGROUND: The aim of this study was to determine the factors that influence self-care agency and daily life activities among the elderly in the northern region of Turkey. METHODS: This study of 372 elderly individuals was conducted between October 13, 2007, and January 25, 2008. The data obtained in this study was collected via a questionnaire and the Katz Basic Activities of Daily Living Scale and Exercise of Self-Care Agency Scale. Descriptive statistics, Student's t tests, one-way analysis of variance, and multiple regression analysis were used to evaluate the data. RESULTS: Regression analysis performed to determine the effects of sociodemographic and clinical features on the self-care agency of the elderly revealed a statistically significant negative relationship. The multiple regression correlation coefficient of this model was R = 0.635, and the corrected R2 value was 0.23. This model determined the self-care agency score of the elderly participants as 23%. The model is statistically significant (p < 0.05). CONCLUSIONS: The scores obtained in this study indicate that the majority of the elderly participants were independent; their levels of self-care agency were determined as falling within the middle level. PMID- 26552196 TI - The reasons students choose to undertake a nursing degree. AB - BACKGROUND: Determining the reasons people choose to study nursing may help educators and managers develop student-focussed and enticing nursing programmes. In Australia, little research has been undertaken with students entering nursing programmes and the reasons for their choice. OBJECTIVES: The aim of this study was to determine why new students choose to enter nursing at university. DESIGN: A descriptive survey design. SETTING: An urban university in Sydney, Australia. PARTICIPANTS: Undergraduate nursing students at the beginning of their first year of study. METHOD: An open-ended question relating to the reasons for students' choice of a nursing programme was included in the survey. The transcribed textual data were content analysed for words related to the students' choice. RESULTS: The students' reasons for entering nursing programmes were both personal and career related, with personal being more dominant. The reasons to start nursing were: being able to help and care for people, job security, the ability to enter tertiary education and the enjoyment or love of nursing. CONCLUSIONS: Nursing remains a career of choice for young and mature students entering university. It is seen to provide security, interest and opportunity to help and care for others. Universities must focus on this as they develop programmes for a generation where multiple changes of career appear inevitable during their lifetime. The nursing profession needs to look at career pathways after graduation that provide these challenges within nursing itself. PMID- 26552197 TI - The challenges of undergraduate mental health nursing education from the perspectives of heads of schools of nursing in Queensland, Australia. AB - The shortage of a skilled mental health nursing workforce is persistent and worsening. Research consistently demonstrates the inability of the comprehensive model of nursing education to meet nursing workforce needs in mental health. Introducing specialisation in mental health at undergraduate level has been suggested as a strategy to address this problem. Exploration of barriers to this educational approach is essential. The aim of this research is to examine with Queensland Heads of Schools of Nursing, the perceived barriers to a specialist mental health nursing stream within an undergraduate nursing programme. Qualitative exploratory methods, involving in-depth telephone interviews with Heads of Schools of Nursing in Queensland, Australia. Data were analysed thematically. Participants encountered a number of barriers revealed in five main themes: academic staffing; staff attitudes; funding and resource implications; industry support; entry points and articulation pathways. Barriers to the implementation of mental health nursing specialisation in undergraduate programmes are evident. While these barriers pose real threats, potential solutions are also evident. Most notably is the need for Schools of Nursing to become more co-operative in mounting mental health nursing specialisations in a smaller number of universities, where specialist expertise is identified. Quality mental health services rely on a sufficiently skilled and knowledgeable nursing workforce. To achieve this it is important to identify and implement the educational approach best suited to prepare nurses for practice in this field. PMID- 26552198 TI - Measures of clinical accuracy and indicators of the nursing diagnosis of delayed surgical recovery. AB - Delayed surgical recovery is a phenomenon of global concern that affects the results and costs of postoperative care. The aim of this study was to verify the accuracy of the defining characteristics of the diagnosis of delayed surgical recovery in patients after the fifth day in postoperative care. A cross-sectional observational study was conducted with 72 surgical patients to measure sensitivity, specificity, positive and negative predictive values, positive likelihood ratios and negative odds ratios. Diagnoses and the area under the ROC curve were analysed to investigate the diagnostic accuracy of each defining characteristic. Most patients were male (65.3%) with an average length of education of 17.4 years (SD = 1.88) and a mean age of 57.39 years (SD = 16.04), and 55 (76.4%) had the diagnosis of delayed surgical recovery. The variable time after surgery showed a statistical relationship with the diagnosis of delayed surgical recovery (p = .012). Seven characteristics showed high positive predictive values: postpones resumption of work/employment activities, fatigue, perception of needing more time to recover, requiring help to complete self-care, report of discomfort, evidence of interrupted healing of the surgical area, and difficulty in moving about. The only factor in the study that was associated with the diagnosis was postoperative surgical site infection (p = .028). PMID- 26552199 TI - Enhancing computer literacy and information retrieval skills: A rural and remote nursing and midwifery workforce study. AB - Nurses and midwives collectively, represent the largest workforce category in rural and remote areas of Australia. Maintaining currency of practice and attaining annual licensure with the Australian Health Practitioners Regulatory Authority (AHPRA) present challenges for individual nurses and midwives and for their health service managers. Engagement with information and communication technologies, in order for geographically isolated clinicians to access ongoing education and training, is considered a useful strategy to address such challenges. This paper presents a pre- and post-test study design. It examines the impact of an online continuing professional development (CPD) program on Australian rural nurses and midwives. The aims of the program were to increase basic skill acquisition in the utilisation of common computer software, the use of the Internet and the enhancement of email communication. Findings from the study demonstrate that participants who complete a relevant CPD program gain confidence in the use of information and communication technologies. Further, increased confidence leads to increased access to contemporary, reliable and important health care information on the Internet, in addition to clinicians adopting email as a regular method of communication. Health care employers commonly assume employees are skilled users of information and communication technologies. However, findings from this study contradict such assumptions. It is argued in the recommendations that health care employees should be given regular access to CPD programs designed to introduce them to information and communication technologies. Developing knowledge and skills in this area has the potential to improve staff productivity, raise health care standards and improve patient outcomes. PMID- 26552200 TI - Learning and assessing competence in reflective practice: Student evaluation of the relative value of aspects of an integrated, interactive reflective practice syllabus. AB - Although the literature is rich with information on the value of reflective practice, there is a paucity of information on techniques to assess whether professionals have learnt this essential skill. In this article, we describe the introduction and evaluation of an innovative, integrated, interactive approach to teaching and assessing competence in reflective practice using an online self directed learning package. As part of a new staff start up scholarship of teaching and learning grant project in an Australian university, we converted an existing one day reflective practice workshop for undergraduate nursing students to an interactive online learning package that could also be applicable for students in other health professions. The assessment of learning in the package was integrated with overall clinical competence assessment using Tanner's Clinical Judgement Model and Lasater's Clinical Judgement rubric to enable immediate online feedback to students on their progress. In this article, we focus on those aspects of the package that students evaluated as most beneficial to their learning, specifically immediate feedback by lecturers guided by Lasater's rubric. PMID- 26552201 TI - Effects of team-based learning on perceived teamwork and academic performance in a health assessment subject. AB - The purpose of this study was to examine the effectiveness of team-based learning (a well-recognized learning and teaching strategy), applied in a health assessment subject, on nursing students' perceived teamwork (team-efficacy and team skills) and academic performance (individual and team readiness assurance tests, and examination scores). A prospective, one-group, pre- and post-test design enrolled a convenience sample of 74 second-year nursing students at a university in Suwon, Korea. Team-based learning was applied in a 2-credit health assessment subject over a 16-week semester. All students received written material one week before each class for readiness preparation. After administering individual- and team-readiness assurance tests consecutively, the subject instructor gave immediate feedback and delivered a mini-lecture to the students. Finally, students carried out skill based application exercises. The findings showed significant improvements in the mean scores of students' perceived teamwork after the introduction of team-based learning. In addition, team-efficacy was associated with team-adaptability skills and team-interpersonal skills. Regarding academic performance, team readiness assurance tests were significantly higher than individual readiness assurance tests over time. Individual readiness assurance tests were significantly related with examination scores, while team readiness assurance tests were correlated with team-efficacy and team-interpersonal skills. The application of team-based learning in a health assessment subject can enhance students' perceived teamwork and academic performance. This finding suggests that team-based learning may be an effective learning and teaching strategy for improving team-work of nursing students, who need to collaborate and effectively communicate with health care providers to improve patients' health. PMID- 26552202 TI - Is there a relationship between the diversity characteristics of nursing students and their clinical placement experiences? A literature review. AB - BACKGROUND: There has been an increase in ethno-cultural, linguistic, and socio demographical diversity in students enrolling in undergraduate nursing programs. Diversity also involves other characteristics, but little is known about how diversity impacts on the clinical experiences of nursing students. AIM: The aim of this review is to identify studies which describe the clinical placement experiences of nursing students who have a broad range of diversity characteristics. METHODS: Major databases were searched and original studies published from 2003 to 30 June 2013 were eligible for inclusion. An expanded definition of diversity was used to include characteristics such as ethnicity, language, age, religion, gender, socioeconomic status, carer responsibilities, sexual orientation and special needs/disability. FINDINGS: Male gender and speaking English as a second language are diversity characteristics associated with a less positive clinical experience. These students are also more likely to leave their nursing program. Mature-aged students and those from ethnic minority groups were also noted to have a less positive clinical experience and in some cases, this also increased attrition. However, it was difficult to determine the impact of these characteristics alone as they appeared to be linked with other characteristics such as financial difficulties and carer responsibilities in the case of mature-aged students, and language and international student status in the case of ethnicity. CONCLUSIONS: Given the significant benefits associated with preparing a diverse nursing workforce, it is an imperative to better understand the impact of diversity on nursing students to ensure that every placement becomes a positive and valuable learning experience. PMID- 26552203 TI - The challenge of nurse innovation in the Australian context of universal health care. AB - As nursing pushes further into the realm of primary health care in Australia, an understanding of the challenges to achieving reasonable federal funding of nursing services needs to be understood. This understanding is underpinned by a comprehensive understanding of the concept of universal health care, how the concept relates to the Australian health care context, and the resultant challenges to innovation in health care service delivery in Australia. Universal health care is a global mission and was the most recent theme for the International Council of Nurses Congress in Australia. Universal health care as a concept represents a fundamental shift from the development and funding of discrete interventions or programmes, to that of developing systems of health care. The three critical elements required are a clear definition of what is considered health care and funded for who, how the system is financed, and evaluation. Australia has a system of universal health care and all three elements are addressed. Organised medicine, a key objector to the introduction of the current approach to universal health care in Australia, soon adapted to it, and now fiercely resists change. Medico centricity poses challenges to sustainability as innovation is inhibited. This challenge is illustrated through consideration of the implementation of the financial policy that gave Nurse Practitioners access as providers and prescribers within Medicare funded services. PMID- 26552204 TI - Psychosocial and environmental distress resulting from a volcanic eruption: Study protocol. AB - AIM: To examine the psychosocial and environmental distress resulting from the 2010 eruption of the Merapi volcano and explore the experience of living in an environment damaged by a volcanic eruption. BACKGROUND: Natural disasters cause psychosocial responses in survivors. While volcanic eruptions are an example of a natural disaster, little is currently known about the psychosocial impact on survivors. Volcanic eruptions also cause degradation of the environment, which is linked to environmental distress. However, little is currently known of this phenomenon. DESIGN: An explanatory mixed method study. METHODS: The research will be divided into three phases. The first phase will involve instrument modification, translation and testing. The second phase will involve a survey to a larger sample using the modified and tested questionnaire. The third phase will involve the collection of interviews from a sub set of the same participants as the second phase. DISCUSSION: Quantitative data will be analyzed to determine the extent of psychosocial and environmental distress experienced by the participants. Qualitative data will be analyzed to explain the variation among the participants. The results of the study will be used to develop strategies to support survivors in the future and to help ameliorate distress. PMID- 26552205 TI - Heart health in Lebanon and considerations for addressing the burden of cardiovascular disease. AB - INTRODUCTION: Lebanon is a small country located at the western boundary of the Middle East. Approximately 40% of health care in Lebanon is financed by the public sector. Cardiovascular diseases in Lebanon are scarcely addressed in the literature raising the need for baseline data on these health condition to be better treated. AIM: To (1) aggregate and define the burden of cardiovascular disease in Lebanon and (2) describe implications for policy, practice and research to improve health outcomes in Lebanon. METHOD: An integrative review was conducted of both peer-reviewed papers and unpublished reports. CINAHL, Medline, Google Scholar and Academic Search Complete were searched along with the websites of The World Health Organization, Ministry of Public Health Lebanon and Central Intelligence Agency of Lebanon. No year limit was applied to our search. RESULTS: The search yielded 28 peer-reviewed articles and 15 reports. Cardiovascular diseases are the leading cause of morbidity and mortality in Lebanon and is also the primary cause of hospital admission. A range of social, political, economic and cultural factors explain the burden of cardiovascular diseases, some of these risks are culture specific such as the arghile smoking and the high rates of familial hypercholesterolemia. Workforce shortage produced by high rates of migrating nurses also has an implication on the patients' outcomes. Conclusion: Much of the presented data are sourced from the gray literature; more research, using systematic and prospective data collection methods, are needed to inform health services planning, delivery and evaluation. Primary care needs to be enhanced to produce better outcomes for a population with high profile of cardiovascular risk factors. PMID- 26552206 TI - History as reflective practice: A model for integrating historical studies into nurse education. AB - The role of history in developing professional identity in nursing is well known, and the discipline of nursing history research continues to flourish. Yet this work often struggles to find its way into undergraduate university nurse education courses. We put forward a model for "history as reflective practice" in which we suggest that historical studies can be used as a form of evidence to develop critical thinking and clinical reasoning, as well as situate nursing practice within its social and political context. In this model, we draw on historical scholarship related to the profession, practice and person, focusing on work which demonstrates nursing's contribution to broader systems of health care. Drawing on Lewenson and Lynaugh's 'history by stealth' approach, curriculum mapping and constructive alignment techniques are used to identify the moments in an existing programme where historical scholarship is relevant to an intended learning outcome. We then use an interdisciplinary team to develop learning activities and assessment tasks drawing on both primary and secondary sources that are then embedded within existing subjects. This model encourages students to consider history as a way of knowing and as a form of evidence within their reflective practice. Furthermore, it creates knowledge that continues to foster and acknowledge nurses', and nursing's, contribution to the development of human health. PMID- 26552207 TI - [Platelets and erectile dysfunction]. AB - Platelets, small pieces of cytoplasm with biological activity, split and fall off the megakaryocytes and mature from the bone marrow. After stimulated, platelets produce nitric oxide to inhibit their own activation and aggregation. Pathologically, the injury of endothelial cells activates platelets and changes their functions. The release of inflammatory mediators and cytokines induces and enhances the development and progression of atherosclerosis, and thereby promotes the occurrence of erectile dysfunction. Besides, platelets and their related functional parameters may serve as important indicators in the diagnosis and treatment of erectile dysfunction. PMID- 26552208 TI - [Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer]. AB - OBJECTIVE: To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy. METHODS: We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry. RESULTS: The relative gray scales in the ADPC and CRPC groups were 0.59 +/- 0.01 and 1.14 +/- 0.02, with statistically significant differences from 0.62 +/- 0.03 in the ADT group (P < 0.05), and the Delta Ct values of Pim-1 were 6.15 +/- 0.34 and 4.56 +/ 0.23 in the former two groups, also with significant differences from 5.11 +/- 0.21 in the latter (P < 0.05). The results of 2-DeltaDelta Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 +/- 25] pg/ml) and CRPC ([870 +/- 23] pg/ml) than in the ADT ([170 +/- 32] pg/ml) and blank control groups (0 ug/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 +/- 0.002 and 0.032 +/- 0.009 in the ADPC group and 0.024 +/- 0.002 and 0.040 +/- 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 +/- 0.001 and 0.019 +/- 0.006) (P < 0.01). CONCLUSION: Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer. PMID- 26552209 TI - [Crypotanshione reduces the expression of metadherin in DU145 prostate cancer cells]. AB - OBJECTIVE: To investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells. METHODS: We treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours. RESULTS: CPT significantly inhibited the proliferation of the DU145 cells in a dose- and time dependent manner (P < 0.05). After treatment with 10 umol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 +/- 4.51), (55.07 +/ 5.67) and (70.84 +/- 4.66)%, respectively, significantly higher than (3.1 +/- 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 umol/L CPT for 48 hours (P < 0.05). CONCLUSION: CPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells. PMID- 26552210 TI - [Indirubin inhibits the proliferation of prostate cancer PC-3 cells]. AB - OBJECTIVE: To explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms. METHODS: We measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot. RESULTS: The viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 umol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 umol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c myc in the Wnt signaling pathway. CONCLUSION: Indirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway. PMID- 26552211 TI - [Effects of long non-coding RNA-HOTAIR on the cell cycle and invasiveness of prostate cancer]. AB - OBJECTIVE: To investigate the expression of long non-coding RNA-HOTAIR in prostate cancer cells and its effects on the growth and metastasis of the cells. METHODS: Using quantitative reverse-transcription PCR (qRT-PCR), we determined the relative expression of HOTAIR in the normal human prostate epithelial cell line RWPE-I and prostate cancer cell lines PC-3 and DU145. We detected the effects of HOTAIR on the cell cycle and invasiveness of prostate cancer cells by RNA interference, flow cytometry, and Transwell mitration assay. RESULTS: The expressions of HOTAIR in the PC3 and DU145 cells were increased 3.2 and 5.7 times, respectively, as compared with that in the normal RWPE-1 cells. After si HOTAIR interference, the prostate cancer cells were arrested in the G2 phase and downregulated in the G1 phase. The invasive ability of the prostate cancer cells was evidently inhibited, with the inhibition rates of 32% and 44% of the PC3 cells and 43% and 34% of the DU145 cells for si-HOTAIR1 and si-HOTAIR2, respectively. CONCLUSION: IncRNA HOTAIR is highly expressed in prostate cancer, which is associated with the growth and invasiveness of prostate cancer cells. HOTAIR is potentially a novel marker for the diagnosis and prognosis of prostate cancer. PMID- 26552212 TI - [Gefitineb inhibits the growth and induces the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro]. AB - OBJECTIVE: To observe the inhibitory effect of gefitineb on the proliferation and its inducing effect on the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro. METHODS: We treated I-10 Leydig testicular cancer cells of mice with gefitineb at 0, 1.25, 2.5, 5, 10, 20, and 40 umol/L. Then we determined the inhibitory effect of gefitineb on the growth of the cells by MTT, detected their early and late apoptosis by Annexin V-FITC/propidium iodide double staining and Hoechst 33258 nuclear staining, respectively, and observed the expressions of apoptosis-related proteins Bcl-2, Bax and caspase 3/9 by Western blot. RESULTS: Compared with the blank control group, gefitineb significantly inhibited the proliferation of the I-10 cells at 10 and 20 umol/L (P < 0.05). The survival rate of the cells was (32.4 +/- 2.8)% (P < 0.01) and their early and late apoptosis rates were (26.7 +/- 4.2)% and (59.33 +/- 10.2)% in the 40 umol/L group, significantly different from those in the control (P < 0.05 and P <0.01). In comparison with the blank control group, gefitineb at 10, 20, and 40 umol/L increased the expression of pro-apoptotic protein Bax by (41.9 +/- 7.1), (60.1 +/ 9.8), and (69.0 +/- 11.3)% (all P < 0.05), decreased that of apoptosis inhibitory protein Bcl-2 by (50.3 +/- 8.9), (63.9 +/- 6.9), and (88.7 +/- 13.9)% (all P < 0.05), and elevated that of the cleft proteins caspase-3 by (69.0 +/- 6.9)% (P < 0.05), (71.5 +/- 8.1)% (P < 0.05), and (110.9 +/- 14.2)% (P < 0.01) and caspase-9 by (51.8 +/- 4.9), (54.7 +/- 6.7), and (43.8 +/- 11.8)% (all P < 0.05). CONCLUSION: Gefitineb can increase the cytotoxicity of I-10 Leydig testicular cancer cells of mice and induce their apoptosis via the mitochondria mediated apoptosis signaling pathway. PMID- 26552213 TI - [Effects and complications of five surgical approaches to the treatment of varicocele: A comparative study]. AB - OBJECTIVE: To compare the effects and complications of subinguinal microscopic ligation, laparoscopic transperitoneal varicocelectomy, laparoscopic retroperitoneal varicocelectomy, open retroperitoneal high ligation, and interventional embolotherapy in the treatment of varicocele. METHODS: We conducted a retrospective study that included 632 varicocele patients treated by subinguinal microscopic ligation (group A, n = 79), laparoscopic transperitoneal varicocelectomy (group B, n = 120), laparoscopic retroperitoneal varicocelectomy (group C, n =137), open retroperitoneal high ligation (group D, n = 283), and interventional embolotherapy (group E, n = 13). We compared the baseline and 3 month postoperative semen parameters, postoperative complications, and pregnancy rate among the five groups of patients. RESULTS: The operation time was longer in groups A ([2.02 +/- 1.25] h) and E ([2.17 +/- 1.02] h) than in the other three groups, while the postoperative hospital stay was the shortest in group E ([1.1 +/- 0.1] d). Intestinal injury or incision bleeding occurred intraoperatively in 2 cases in group B and 1 case in group E. Postoperative scrotal edema developed in 3.7, 17, 10, and 19% of the patients in groups A, B, C, and D, respectively, but not in group E. The rate of 1-year recurrence was the lowest in group A (1.6%) and highest in group E (22%). Sperm concentration and the percentages of progressively motile sperm and morphologically normal sperm were improved postoperatively in all the patients (P < 0. 05), but there were no statistically significant differences among the five groups either in the above three parameters or in the postoperative pregnancy rate (P > 0. 05). CONCLUSION: In the surgical treatment of varicocele, laparoscopic retroperitoneal approach involves short operation time and few complications, subinguinal microscopic ligation has the advantages of little injury, rapid recovery, and few complications but requires specialized microsurgical techniques, and interventional embolotherapy leaves no incision scar and needs only local anesthesia and 1-day postoperative hospital stay, which is uitable for those with a contraindication to anesthesia. PMID- 26552214 TI - [Testicular teratoma in children: Analysis of 64 cases]. AB - OBJECTIVE: To improve the diagnosis and treatment of testicular teratoma in children by analysis of clinical data. METHODS: We retrospectively analyzed the clinical data about 64 cases of testicular teratoma treated in the Children's Hospital of Chongqing Medical University from 1995 to 2014. RESULTS: Sixty-one of the cases presented painless scrotal mass with a sense of bearing down and the other 3 cases were confirmed because of empty scrotum diagnosed as cryptorchidism. The level of serum alpha fetal protein ( AFP) was obviously increased in 46 cases but normal in the other 18 preoperatively. Ultrasonography manifested abnormal inhomogeneous echo zones with calcification or necrosis. X ray examination presented patchy or curvilinear high-density shadows in 28 cases. Forty-one of the patients underwent testis-sparing surgery (TSS) , 20 received high inguinal orchiectomy, and 3 refused surgical treatment. Pathological examination revealed 3 mature germinal layers in the 49 cases of mature teratoma and immature germinal tissue, including the original neural tube, and 11 cases of immature teratoma. The mature cases were exempted from chemotherapy, while the immature cases received the combination of cisplatin, etoposide, and bleomycin (PEB). The patients were followed up for 2 years postoperatively, which revealed no recurrence or metastasis. CONCLUSION: Most children with testicular teratoma presented painless scrotal mass with a sense of bearing down and with abnormal serum AFP in most cases. Ultrasonography and plain radiography of the scrotum contribute to the diagnosis of the tumor. TSS is the main treatment option and intraoperative frozen-section can help the surgeons decide on the surgical mode. Postoperative chemotherapy is necessitated for immature teratoma but not for mature cases. PMID- 26552215 TI - [Polypropylene mesh for testicular prothesis implantation: A report of 57 cases]. AB - OBJECTIVE: To search for an optimum method for testicular prothesis implantation in the treatment of testis loss. METHODS: We retrospectively analyzed the surgical methods and outcomes of 53 cases of terminal prostate cancer and 4 cases of unilateral testicular torsion treated by implantation of testicular prothesis with the polypropylene mesh. RESULTS: The 57 male patients all received testicular prothesis with the polypropylene mesh. All the patients were satisfied with the appearance and size of the scrotum after surgery. No scrotal hematoma, prosthesis infection, or autoimmune disease occurred postoperatively. CONCLUSION: Testis loss is not a rare condition clinically, for the treatment of which surgical implantation of testicular prothesis with the polypropylene mesh can achieve both a fine tissue compatibility and a desirable scrotal appearance. PMID- 26552216 TI - [Intracytoplasmic sperm injection does not improve the clinical outcomes of the males with 100% teratozoospermia]. AB - OBJECTIVE: To investigate whether intracytoplasmic sperm injection (ICSI) can improve the clinical outcomes of the male patients with 100% teratozoospermia. METHODS: We retrospectively analyzed the clinical data of 152 couples undergoing in vitro fertilization-embryo transfer (IVF-ET), including 75 cycles of IVF and 77 cycles of ICSI. We compared the rates of normal fertilization, high-quality embryos, transferrable embryos, implantation, clinical pregnancy, and abortion between the two groups. RESULTS: In the 100% teratozoospermia patients the number of transferrable embryos was significantly lower in the IVF than in the ICSI group (78.91% vs 84.92%, P < 0.05), while the rates of normal fertilization and implantation were higher in the former than in the latter (60.26% vs 57.87% and 48.00% vs 39.55%, both P > 0.05). There were no statistically significant differences between the two groups in the female age, Gn days, Gn dose, BMI, infertility duration, endometrial thickness, and basal serum FSH and E2. CONCLUSION: ICSI cannot improve the clinical outcomes of the male patients with 100% teratozoospermia. PMID- 26552217 TI - [Morinda Officinalis How improves cellphone radiation-induced abnormality of LH and LHR in male rats]. AB - OBJECTIVE: To investigate the effects of Morina Officinalis How (MOH) on the abnormal levels of serum luteotrophic hormone (LH) and LH receptor (LHR) in the testis tissue induced by cellphone radiation (CPR) in rats. METHODS: Fifty adult male SD rats were randomly divided into five groups of equal number: sham CPR, untreated CPR, negative double distilled water (DDW) control, aqueous MOH extract, and alcohol MOH extract. All the animals were exposed to mobile phone radiation except those of the sham CPR group. Then, the rats of the latter two groups were treated intragastrically with MOH at 20 g per kg of the body weight per day in water and alcohol, respectively. After 2. weeks of treatment, all the rats were sacrificed for measurement of the levels of serum LH and LHR in the testis tissue. RESULTS: The levels of serum LH and LHR were 30.15 +/- 8.71 and 33.28 +/- 6.61 in the aqueous MOH group and 0.96 +/- 0.06 and 0.94 +/- 0.08 in the alcohol MOH group, both significantly decreased as compared with the negative DDW controls (P < 0.05), but with no remarkable difference between the two MOH groups (P > 0.05). CONCLUSION: MOH can improve CPR-induced abnormality of LH and LHR in adult male rats. PMID- 26552218 TI - [Protective effect of Danxuetong injection against testicular injury after testis torsion/detorsion in rats]. AB - OBJECTIVE: To investigate the protective effect of Danxuetong injection (DXT, a combination of Danshen and Xueshuantong injections) against testicular ischemia reperfusion injury following testis torsion/detorsion in rats. METHODS: Thirty two 4-week-old healthy male SD rats were randomly divided into four groups of equal number: sham operation, normal saline, single DXT injection, and successive DXT injection. The rat models of testicular ischemia-reperfusion injury were established by 2-hour 720-degree torsion/detorsion of the unilateral testis. At 6 weeks after modeling, the rats were killed and their testes were harvested for measure- ment of testicular coefficients, sperm counts, sperm motility, and the levels of total anti-oxidative capacity (T-AOC) , superoxide dismutase (SOD) , nitric oxide synthase (NOS) , and malondialdehyde ( MDA) in the testis tissue. RESULTS: Compared with the rats of the normal saline group, those of the single DXT injection and successive DXT injection groups showed significant increases in the testicular coefficient (0.11 +/- 0.03 vs 0.35 +/- 0.04 and 0.40 +/- 0.06, P < 0.05), sperm count ([0.46 +/- 0.10] vs [1.44 +/- 0.50] and [3.00 +/- 1.28] x10(9)/ml, P < 0.05), sperm motility ([13.63 +/- 14.04] vs [39.63 +/- 5.04] and [76.31 +/- 3.67]%, P < 0.05), the activity of SOD (72.76 +/- 5.58 vs 116.25 +/- 8.83 and 133.20 +/- 13.84, P < 0.05), and the level of T-AOC (5.58 +/- 1.07 vs 13.34 +/- 5.81 and 19.21 +/- 5.69, P < 0.05), but a remarkable decrease in the content of MDA (42.38 +/- 8.94 vs 20.94 +/- 5.65 and 15.02 +/- 1.03, P < 0. 05) in the injured testes. CONCLUSION: DXT can effectively rid the testis tissue of oxygen free radicals, improve sperm count and motility by antioxidation, and protect the testis tissue of prepubertal rats against testicular ischemia reperfusion injury after testis torsion/detorsion. It also has a protective effect on the contralateral testis, and successive injection has a better effect than single injection of DXT. PMID- 26552219 TI - [Kidney-tonifying Chinese medicine for male infertility: A systematic review of randomized controlled trials]. AB - OBJECTIVE: To systematically evaluate the efficacy and safety of kidney-tonifying traditional Chinese medicine in the treatment of male infertility. METHODS: Based on the principles and methods of Cochrane systematic reviews, we searched CNKI, VIP, and Wanfang databases from inception to December 2012 for randomized controlled clinical trials addressing the treatment of male infertility with kidney-tonifying traditional Chinese medicine. According to the inclusion and exclusion criteria and retrieval strategies, we extracted the data, evaluated the quality of the included literature, and conducted meta-analysis using the RevMan 5. 2 software. RESULTS: Twenty trials involving 2,272 patients were included, and the sample size of each study was from 60 to 270 cases. All the studies were graded as of poor quality, with Jadad scores of no more than 3 points. The results of meta-analysis showed that the total effectiveness rate of traditional Chinese medicine versus Western medicine on male infertility was RR = 1.71, 95% CI 1.19-2.47, and that of Chinese-Western combined therapy versus Western medicine was RR = 1.15, 95% CI 1.01-1.30. Both traditional Chinese medicine and Chinese-Western combined therapy showed a significantly better total effectiveness than Western medicine alone in improving the pregnancy rate without serious adverse reactions. CONCLUSION: Due to the poor methodological quality and high heterogeneity of the included studies, the evidence for the efficacy and safety of kidney-tonifying traditional Chinese drugs in the treatment of male infertility is of but limited value, and further validation is needed by more high-quality studies. PMID- 26552220 TI - [Application of saw palmetto fruit extract in the treatment of prostate diseases]. AB - Saw palmetto fruit extract (SPE), as a herbal product, is widely used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Recent studies show that SPE also has some therapeutic effects on chronic prostatitis, prostate cancer, sexual dysfunction, and so on. This article presents an overview on the application of SPE in the treatment of BPH, prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome, with a discussion on its action mechanisms. PMID- 26552221 TI - [Epithelial mesenchymal transition in prostate cancer: Advances in current research]. AB - Epithelial mesenchymal transition (EMT) is a process of normal cell physiological development, in which epithelial cells transform into mesenchyme cells through a specific program. EMT plays a key role in inflammatory reaction, cell development, tumor invasion, and metastasis and has an interrelation with prostate cancer stem cells. Recent researches show the involvement of EMT in the development and metastasis of prostate cancer. This article reviews the specific roles and action mechanisms of EMT in the progression of prostate cancer. PMID- 26552222 TI - [Advances in the studies of concealed penis]. AB - Concealed penis is usually found in children, which affects the patients both physiologically and psychologically. Some of the patients are wrongly treated by circumcision, which may bring about serious consequences to the sexual life of the patients in their adulthood. In the recent years, this disease has been receiving more and more attention from both doctors and parents. However, controversies remain as to its classification, pathogenesis, pathology, and treatment. This paper focuses on the understanding and advances in the studies of concealed penis. PMID- 26552223 TI - [Computed tomography in evaluating the development of different types of pulmonary fibrosis in patients with interstitial lung diseases]. AB - OBJECTIVE: to assess the favorable and unfavorable types of lung tissue fibrotic changes in patients with interstitial lung diseases (ILD) detected by high resolution computed tomography (HRCT). MATERIAL AND METHODS. The results of examinations were analyzed in 385 patients: 181 with respiratory organ sarcoidosis, 130 with fibrosing alveolitis, 36 with histiocytosis X, and 38 with lymphangiolciomyomatosis. All the patients underwent HRCT; the data were compared with the results of comprehensive functional study of external respiration (CFSER), histological examination (in 70.1%), and the pattern of the disease. RESULTS: Comparison of the clinical and functional course of ILD with the types of lung tissue fibrotic changes detected by HRCT and morphological examination showed that the favorable types of pulmonary fibrosis included stringy central and peripheral interstitial fibrotic changes and the atelectatic type of fibrosis, the occurrence of which failed to affect the development of obvious perfusion and diffusion disorders and to give rise to respiratory failure. The unfavorable types of pulmonary fibrosis included the peripheral pulmonary interstitial fibrotic changes (acinar fibrosis, honeycomb lung), which led to restrictive changes and perfusion disorders, which were accompanied by significant respiratory failure, decreases in quality of life and survival, as well as fibrotic changes in the walls of long-lasting air-containing cysts and a fibrotic Aevity mass that resulted Ind complications (pulmonary hemorrhage, pneumothorax, and pneumomediastinum). CONCLUSION: The type of pulmonary fibrosis development is one of the major prognostic criteria for he course of ILD. HRCT makes it possible to assess its clinical picture as a whole and to reveal the type of development of fibrotic changes, their extent, the degree of involvement of the tracheobronchial tree in the process (formation of different types of bronchiectasis), concomitant extrapulmonary changes that may be clinically and functionally relevant (chest bone frame deformation, varying pleural changes, vascular disorders). Estimation of prognosis of the disease is most effective in comparing clinical, morphological, HRCT, and CFSER data. PMID- 26552224 TI - [Radio morphological changes in the femoral and tibial condyles in patients with arthrosis deformans of the knee]. AB - OBJECTIVE: to investigate the quantitative X-ray manifestations of gonarthrosis in patients in different age groups. MATERIAL AND METHODS: The results of radiography, computed tomography, and 64-slice multidetector computed tomography (MDCT) were analyzed in 86 patients aged 18 to 70 years with arthrosis deformans of the knee. RESULTS: Knee radiographic anatomic changes in arthrosis deformans are accompanied by the characteristic rearrangement of the femoral and tibial condyles. Quantitative bone density changes appear as an overall decrease in the bone mineral density of the femoral and tibial condyles in 18-35-year-old patients with arthrosis deformans (p<0.05) and a relative increase in that of medial tibial condyles in patients older than 55/60 years, in those with genu varum in particular. CONCLUSION: In the patients with arthrosis deformans, the bone radio morphological changes detected by MDCT have a much wider range of qualitative and quantitative characteristics. The data on condylar bone density are directly related to a treatment choice. Data postprocessing using the current visualization programs of working stations identifies minor bone structural changes that are also of importance in solving the tactical problems of medical and surgical treatments. PMID- 26552225 TI - [Magnetic resonance semiotics of prostate cancer according to the PI-RADS classification. The clinical diagnostic algorithm of a study]. AB - OBJECTIVE: to elaborate the magnetic resonance imaging (MRI) signs of prostate cancer (PC) in accordance with the PI-RADS classification during multiparametric MRI (mpMRI). MATERIAL AND METHODS: A total of 89 men aged 20 to 82 years were examined. A control group consisted of 8 (9%) healthy volunteers younger than 30 years of age with no urological history to obtain control images and MRI plots and 20 (22.5%) men aged 26-76 years, whose morphological changes were inflammatory and hyperplastic. The second age-matched group included 61 (68.5%) patients diagnosed with prostate cancer at morphological examination. A set of studies included digital rectal examination, serum prostate-specific antigen, and transrectal ultrasound-guided prostate biopsy. All the patients underwent prostate mpMRI applying a 3.0 T Achieva MRI scanner (Philips, the Netherlands). RESULTS: The patients have been found to have mpMRI signs that were typical of PC; its MRI semiotics according to the PI-RADS classification is presented. Each mpMRI procedure has been determined to be of importance and informative value in detecting PC. CONCLUSION: The comprehensive mpMRI approach to diagnosing PC improves the quality and diagnostic value of prostate MRI. PMID- 26552226 TI - [Determination of the efficiency of single-photon emission computed tomography with 99mTc-HMPAO-labelled leukocytes in the diagnosis of myocarditis: Comparison of scintigraphic and histological data]. AB - OBJECTIVE: to determine the efficiency of single-photon emission computed tomography (SPECT) with 99mTc-HMPAO- labelled leukocytes in diagnosing myocarditis, by comparing scintigraphic and histological data. MATERIAL AND METHODS: The investigation enrolled 35 patients with suspected myocarditis, who were planned to undergo coronaroventriculography or intervention with endomyocardial biopsy. Prior to endomyocardial biopsy, all the patients underwent myocardial scintigraphy using 99mTC-exametazime-labelled leukocytes. The results of myocardial scintigraphic and histological examinations were compared. RESULTS: Abnormal myocardial 99mTc-HMPAO-labelled leukocyte accumulation was detected in 7 (20%) examinees. Myocarditis was histologically verified in 9 (25.7%) persons. Our findings showed that the sensitivity of 99mTc-HMPAO-labelled leukocyte SPECT in diagnosing myocardial inflammatory changes was 62%; its specificity and diagnostic accuracy were 92% and 85%, respectively. Conclusion. 99mTc- HMPAO labelled leukocyte scintigraphy is today one of a few procedures for the primary noninvasive diagnosis of myocardial inflammation. However, in view of its sufficiently low sensitivity and laboriousness and the sigh cost of consumables, the technique is irrationally used in routine clinical practice. PMID- 26552227 TI - [Cystic duplication of the jejunum]. AB - The paper presents a clinical case of jejunal duplication, a rare anomaly of the gastrointestinal tract. It describes an algorithm for hospital diagnostic and therapeutic measures. The capacities of radiodiagnostic studies, such as ultrasonography and magnetic resonance imaging, applied to this clinical case, are analyzed. The paper is supplemented by a concise review of the literature. An update suggests that there are diagnostic difficulties in this anomaly, even when a complete set of radiation techniques is applied and trained specialists participate. PMID- 26552228 TI - [Phantom kidney at angionephroscintigraphy]. AB - Based on the analysis of the data available in the literature and own clinical observations, the authors consider the diagnostic value of the little known scintigraphic phantom kidney phenomenon, a vascular pool that is detected at the angiographic stage of 99mTc-DTPA dynamic renal scintigraphy and that mimics a removed or absent kidney. The paper describes two cases of the phantom kidney. In one case, the phantom kidney detected on the side of nephrectomy manifested a kidney cancer recurrence in the bed of the removed organ; in the other, the kidney-like vascular pool in the patient with left-sided pelvic dystopic kidney was due to the recording of the intestinal vasculature at the site of the expected kidney location. Adherence to a number of methodical conditions for conducting a study, as well as combined single-photon emission computed tomography/computed tomography examination will be able to avoid interpretation errors and to ensure an adequate further diagnostic algorithm. PMID- 26552229 TI - [Radiographic assessment of pulmonary hypertension: Methodical aspects]. AB - Pulmonary hypertension is a menacing complication of a number of diseases, which is responsible for high mortality rates and considerably poorer quality of life in a patient. The timely detection for pulmonary hypertension allows timely initiation of treatment, thus improvement in prognosis in the patient. Chest X ray is the most commonly used radiographic technique for various causes. Physicians' awareness about the radiographic manifestations of pulmonary hypertension may contribute to the earlier detection of this severe disease. Owing to the natural contrast of reflected structures, a chest X-ray film gives a unique opportunity to assess pulmonary circulation vessels, to reveal the signs of pulmonary hypertension, and to estimate trends in the course of the disease. The paper details a procedure for analysis and the normal radiographic anatomy of pulmonary circulation vessels, gives the present classification of pulmonary hypertension, and sets forth its X-ray semiotics. PMID- 26552230 TI - [Magnetic resonance imaging of the liver and spleen in the diagnosis of storage diseases]. AB - Storage diseases (thesaurismoses, storage reticuloses) are the common name of a large group of hyperplastic non-leukemic diseases characterized by congenital or acquired metabolic disturbances and abnormal accumulation of metabolic products in blood and/or cells of different organs and by hyperplasia of mononuclear phagocyte elements in the liver, spleen, bone marrow, lymph nodes, and other organs, which makes the diseases systemic. Among the imaging techniques for diffuse liver diseases, ultrasonography and X-ray computed tomography are most commonly used for their diagnosis and follow-up. Magnetic resonance imaging (MRI) has the highest sensitivity and specificity in diagnosing liver diseases. The paper considers the current MRI procedures that are used to diagnose storage diseases and to quantify found changes. For Gaucher's disease, the potentials of novel techniques, such as MR spectroscopy, diffusion-weighted imaging (DWI), and chemical shift imaging (Dickson's method) for the estimation of revealed changes, are described. For hemochromatosis, the contribution of T2 WI to the quantification of iron overload in the liver parenchyma is depicted, which is an alternative invasive procedure in its determination. Incorporation of MRI into the examination algorithm for patients with storage diseases will be able to improve the detection of these rare diseases and to monitor the efficiency of performed therapy. PMID- 26552231 TI - [Radiographic evaluation of cone-beam computed tomography for oral implants: maxillary sinus]. AB - Cone-beam computed tomography (CBCT) has an important function in understanding implant operations. CBCT can be used to evaluate the basic condition of implant site before implant operation and decide whether it is suitable for implanting. CBCT also ensures whether the direction of implant and the operation method are satisfactory. CBCT can be used pre- or post-operation as long as the case involves the maxillary sinus. Clinical implant cases using CBCT were introduced to evaluate the maxillary sinus pre- or post-operation. PMID- 26552232 TI - [Dentists should improve the ability to deal with medical emergencies in dental clinic]. AB - In recent years, the number of outpatients in stomatological hospital is in increasing year by year and being accompanied by the corresponding medical risks. One of the risks which may endanger the patient life is medical emergency which need emergency treatment by the dentists in dental clinical practice. The most common emergency type is syncope, followed by hyperventilation, drug overdose, adrenaline reaction and hypertension, etc. Unexpected events mainly occurred at the end of the treatment and before leaving the dental clinic, during or immediately after the local anesthesia, in the treatment process. Tooth extraction related emergency is the most frequently occurring emergency, followed by the local anesthesia related ones. It's strongly suggested that dentists should pay more attention to outpatient clinical emergency treatment, and related knowledge and skills training should be offered to improve the ability to handle medical emergencies. PMID- 26552233 TI - [Variations in protein concentration and albumin/globulin ratio of whole unstimulated saliva obtained from healthy people and patients with chronic periodontitis]. AB - OBJECTIVE: We detected and analyzed the clinical values of total protein (TP), albumin (ALB), globulin (GLB), and ALB/GLB ratio (A/G) of whole unstimulated saliva of healthy people to determine the time of day when saliva composition is relatively stable. We compared the protein concentration and A/G of whole unstimulated saliva of patients with chronic periodontitis with those of healthy volunteers to provide references for diagnostic methods and clinical applications of saliva. METHODS: The whole saliva of 37 healthy subjects were collected at 8:00, 9:30, 11:30, 13:00, 16:30, and 21:00. Meanwhile, the whole saliva of 24 patients with periodontitis was collected in the morning. Bicinchoninic acid method was used to detect the TP content. Saliva ALB was detected by GF-D800 semi automatic biochemical analyzer, and the GLB and A/G were calculated. Finally, the results were statistically analyzed using SPSS 19.0. RESULTS: Salivary protein compositions were stable in the morning on an empty stomach. Healthy people: TP, (1 354.35+/-389.52) ug.mL-1; ALB, (139.55+/-27.19) ug.mL-1; GLB, (1 211.80+/ 360.73) ug.mL-1; A/G, 0.126 3+/-0.041 7. Subjects with chronic periodontitis: TP, (2 611.56+/-231.62) ug.mL-1; ALB, (296.27+/-17.34) ug.mL-1; GLB, (2 315.69+/ 221.67) ug.mL-1; A/G, 0.156 2+/-0.017 3. The contents of TP, ALB, and GLB in healthy individuals at different periods within a day showed significant differences (P<0.05), which were mainly reflected in the levels before and after meals. No significant difference was detected in A/G. The concentrations of TP, ALB, and GLB were significantly increased in patients with chronic periodontitis compared with those in healthy volunteers. However, no significant difference existed in A/G. CONCLUSION: Salivary protein compositions are more stable in the morning than in other periods. Thus, mornings can be set as the time of specimen collection in future research. The concentrations of TP, ALB, and GLB in patients with chronic periodontitis are higher than those in healthy people. PMID- 26552234 TI - [Expression of connexin 43 gene during early dental development in zebra fish]. AB - OBJECTIVE: This study aims to investigate the expression of connexin 43 (cx43) gene during early development in zebra fish and provide a foundation for further research of cx43 gene in tooth development. METHODS: Total RNA was extracted within 72 h after fertilization of zebra fish embryos and then reversed transcribed to generate the cDNA library. The specific fragments of the cx43 gene were then cloned and connected to the PGEMT vector. After confirming the constructed plasmid, the corresponding RNA polymerase was chosen, and the digoxin labeled anti-sense mRNA probe of cx43 was synthesized in vitro. The cx43 gene expression of zebra fish indifferent stages was carried out by in situ hybridization. The relationship of the cx43 gene expression and anatomy of the pharyngeal teeth were compared by alizarin red staining. RESULTS: The mRNA antisense probe of cx43 was acquired. The positive signal of sepia was observed in the different stages of zebra fish pharyngeal teeth after fertilization. After fertilization for 9 days, the expression site of cx43 in situ hybridization was overlapped in accordance with the anatomical site of the pharyngeal teeth. CONCLUSION: cx43 gene participates in tooth development and mineralization process and plays a crucial role in later mineralization. PMID- 26552235 TI - [Topography and mechanical property of goat temporomandibular joint disc cells]. AB - OBJECTIVE: This study is performed to investigate the cell topographies and biomechanical properties of two different types of temporomandibular joint (TMJ) discs from goats by using JPK Nano Wizard 3 biological atomic force microscopy (AFM). This process provides a guideline for selecting seed cells for TMJ disc tissue engineering. METHODS: TMJ disc cells from primary goats were cultured by monolayer culture method. AFM was used to contact scan the topographies of the two types of TMJ disc cells under physiological environment. Approximately 20 chondrocyte-like and fibroblast-like cells were selected randomly to plot the force-versus-distance curves of the cytoplasm and nucleus. Young's modulus and adhesion were analyzed by JPK Data Processing. RESULTS: The triangle shapednucleus of the chondrocyte-like cell occupied a large portion of the cell. Cytoskeleton was arranged dendritically on the surface. Pseudopodia were extended from cell edges. The spindle-shaped nucleus of the fibroblast-like cell occupied a significantly larger region compared with the cytoplasmic region. Cytoskeleton was arranged regularly. Cell edges were smooth with less pseudopodia extended. No difference was found in the surface roughness between the two types of cells. According to the force-versus-distance curves, the Young's moduli of the two types of cells were not statistically different (P>0.05), but differences were found in the cytoplasmic regions (P=0.047). No statistical difference was found in the adhesions between the two types of cells (P>0.05). CONCLUSION: The AFM topography and curves were compared and analyzed. The two types of TMJ disc cells exhibited significantly different topographies, but only slight difference in their mechanical abilities. PMID- 26552236 TI - [Study on lingual mucosa carcinogenesis of C57BL/6 mice induced by 4 nitroquinoline 1-oxide]. AB - OBJECTIVE: This study aimed to induce carcinogenesis of lingual mucosa in C57BL/6 mice by feeding them 4-nitroquinoline 1-oxide (4NQO) solution. METHODS: A total of 85 C57BL/6 mice were randomly divided into distilled water control group (DD group, n=5), 1,2-propylene glycol control group (PG group, n=5), and experimental group (EP group, n= 75). The mice in the experimental group were medially fed in 15 cages. By contrast, the mice in DD, EP, and PG groups were watered with distilled water, 50 mg.L-1 4NQO solution, and 1,2-propylene glycol solution. The mice in EP group were executed every two weeks from week 0, and the mice in the control groups were sacrificed at the 28th week. The mice were weighed. Mucosal lesions were measured by macroscopic observation and histopathologic detection. RESULTS: One mouse in EP group died of unknown reason. The weight of the mice in EP group presented weight loss compared with the mice in DD and PG groups after the 24th week. Seventy-nine macroscopic lesions were observed in the lingual mucosa, oral floor, and upper palatal and buccal mucosa. A total of 70 macroscopic lesions (88.6%) were located in the lingual mucosa. Mucosal lesions changed from simple hyperplasia to squamous cell carcinomas. Well-differentiated squamous cell carcinomas were observed in all mice of EP group by pathological section at the 28th week. No lesion was found in the mice of DD and PG groups. CONCLUSION: The animal model of lingual squamous cell carcinomas was successfully established. The periods from 12th to 16th week and 20th to 28th week were the ideal times for the research on pathogenesis of early and medial-advanced stage during carcinogenesis of squamous cell carcinomas. PMID- 26552237 TI - [Effect of topically applied recombinant adenovirus of adiponectin on bone defect repair]. AB - OBJECTIVE: To investigate the effect of local administration of recombinant adenovirus of human adiponectin (hAPN) Ad-hAPN-EGFP on tibial defect repair of SD rats. METHODS: Tibial defect (2 mm) models of 36 SD rats (72 sides) were randomly divided into three groups (A, B, and C; n=24). The three groups were injected with Ad-hAPN-EGFP, Ad-EGFP, and normal saline, respectively, during operation and the day after operation. A week after the operation, the expression of hAPN and osteogenesis-related factors were detected by real-time polymerase chain reaction. Three weeks after operation, the tibias were examined by micro-computed tomography, hematoxylin-eosin staining, and Masson staining to evaluate the restoration of bone defects. RESULTS: 1) The hAPN expression was detected in group A but not in groups B and C. Osteogenesis-related factors expression of group A was significantly higher than that of the other groups (P<0.05). 2) Osteogenesis (including bone mineral density, relative bone volume, trabecular number and trabecular thickness) in group A were more evident than those in groups B and C (P<0.05). No significant differences were found between groups B and C (P>0.05). CONCLUSION: Local administration of recombinant adenovirus Ad hAPN-EGFP may be an effective strategy to improve the restoration of bone defects in vivo. PMID- 26552238 TI - [Programmed death ligand 1 negatively regulates inflammatory response of chronic periodontitis]. AB - OBJECTIVE: To investigate whether programmed death ligand 1 (PD-L1) expressed in the periodontal tissue of chronic periodontitis and the correlativity of PD-L1 and different degrees of chronic periodontitis, provide experience for immunoregulation mechanism, clinical treatment and prognosis of chronic periodontitis. METHODS: Gingiva and periodontal tissue of healthy people and chronic periodontitis patients were collected. Based on clinical probing, periodontal tissue were classified into three groups: periodontal tissues of healthy people, periodontal tissue of mild chronic periodontitis, periodontal tissue of severe chronic periodontitis. Fluorescent quantitation polymerase chain reaction was applied to explore the expression of PD-L1 mRNA in the periodontal tissue of the different groups. Western blot and immunohistochemistry method were utilized to test the expression of PD-L1 protein in the periodontal tissue of the different groups. Combining with clinical image data, the relationship between differentially expressions of PD-L1 and different degrees of chronic periodontitis was analyzed. RESULTS: The relative expression quantity of PD-L1 in the periodontal tissue of the mild chronic periodontitis was significantly higher that of the severe chronic periodontitis (P<0.01). The relative expression quantity of PD-L1 in the periodontal tissue of healthy subjects and severe chronic periodontitis had no statistical significance (P>0.05). CONCLUSION: The expression of PD-L1 in the periodontal tissue negativelv regulates inflammatory periodontal tissue damage. PMID- 26552239 TI - [Effects of Icariin promotion on proliferation and osteogenic differentiation of human periodontal ligament stem cells]. AB - OBJECTIVE: To evaluate the effects of Icariin (ICA) on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro and in vivo. METHODS: An enzymatic digestion block was used in vitro to culture hPDLSCs, which were separated and purified by limited dilution cloning. The hPDLSCs were identified using cell-surface markers and cocultured with 1 x 10(-7) mol.L-1 ICA solution. The proliferation ability of these cells was determined by thiazolyl blue tetrazolium bromide (MTT) assay. After staining with alkaline phosphatase (ALP), osteogenesis was detected by enzyme-linked immunosorbent assay. Osteoblast-related genes were analyzed by reverse transcription-polymerase chain reaction. Alizarin red staining was performed to measure the level of calcium deposition. The hPDLSCs were cocultured with 1 x 10( 7) mol.L-1 ICA and nano-hydroxyapatite scaffolds in vivo before transplantation into subcutaneous tissues of nude mice. Osteogenic abilities were histochemically analyzed after 30 days of induction. RESULTS: The hPDLSCs were affected by 1 x 10(-7) mol.L-1 ICA, and MTT assay showed that the proliferation of the groups treated with ICA in vitro was better than that of the control groups on the second day. The ALP activity of the treated hPDLSCs was significantly enhanced after cell culture for 3, 5, and 7 days. The gene expression of osteoblastic markers was also significantly enhanced after 7 days. The deposition of mineralization after incubation with 1 x 10(-7) mol.L-1 ICA increased compared with the control after cell culture for 14, 21, and 28 days. Furthermore, the bone expression of the treatment groups in vivo was significantly enhanced compared with that of the control groups. CONCLUSION: Treatment with 1 x 10(-7) mol.L-1 ICA can significantly promote proliferation and differentiation of hPDLSCs in vitro and in vivo. ICA can effectively function as a bioactive growth factor in periodontal tissue engineering to replace traditional growth factors. PMID- 26552240 TI - [Expression of bone morphogenetic protein receptor 2 in cleft mouse embryonic palate induced by retinoic acid]. AB - OBJECTIVE: To investigate the effects of all-trans retinoic acid (atRA) on the function of bone morphogenetic protein receptor 2 (BMPR2) expression in embryonic palate. METHODS: Cleft palate mice model was established by atRA. On gestation day (GD) 15 and GD 17, the pregnant mice were killed to obtain the embryos from the uteri. The embryonic palates were stained with hematoxylin-eosin, and the remaining sections were used for the immunohistochemistry of BMPR2 detection. Reverse transcription-polymerase chain reaction was performed to detect the expression levels of Bmpr2 mRNA. RESULTS: In the atRA-treated group, short extensions and failure to fuse with each other were observed. The positive expression of BMPR2 was detected in developing palatal process from GD 15 to GD 17 in the control group. Compared with those of the control group, BMPR2 protein and Bmpr2 mRNA decreased in the atRA-treated group (P<0.05). CONCLUSION: The treatment of pregnant mice with retinoic acid produces small palatal shelves in their fetuses and down-regulates BMPR2 expressions. PMID- 26552241 TI - [Effects of interleukin-18 and hypoxia-inducible factor-1alpha in serum and gingival tissues of rat model with periodontitis exposed to chronic intermittent hypoxia]. AB - OBJECTVE: This study evaluates the expression of interleukin-18 (IL-18) and hypoxia-inducible factor (HIF)-lalpha in rat periodontitis model exposed to normoxia and chronic intermittent hypoxia (CIH) environments. The possible correlation between periodontitis and obstructive sleep apnea-hypopnea syndrome (OSAHS) was also investigated. Methods: Thirty-two Sprague-Dawley (SD) rats were randomly assigned into four groups: normoxia control, normoxia periodontitis, hypoxia control, and hypoxia periodontitis groups. The periodontitis models were established by ligating the bilateral maxillary second molars and employing high carbohydrate diets. Rats in hypoxia control and hypoxia periodontitis groups were exposed to CIH treatment mimicking a moderately severe OSAHS condition. All animals were sacrificed after eight weeks, and the clinical periodontal indexes were detected. The levels of IL-18 and HIF-1alpha in serum and gingival tissues were determined using enzyme-linked immunosorbent assay (ELISA). The correlation between attachment loss (AL) and the levels of IL-18 and HIF-lalpha in hypoxia periodontitis group was evaluated. RESULTS: The levels of IL-18 and HIF-lalpha in hypoxia periodontitis group were significantly higher than that in normoxia periodontitis and hypoxia control groups (P<0.05). Furthermore, the levels of IL 18 and HIF-lalpha in serum (r-0.792, r=0.753, P<0.05) and gingival tissues (r 0.817, r=0.779, P<0.05) were positively correlated with AL. CONCLUSION: CIH could aggravate the destruction of periodontal tissues, which is correlated with IL-18 and HIF-lalpha levels. PMID- 26552242 TI - [Analysis of the color difference between discolored teeth and corresponding shade tabs in Vitapan Classical shade guide]. AB - OBJECTIVE: To analyze whether Vitapan Classical shade guide could be used to evaluate effectively the effect of tooth whitening. METHODS: A total of 67 patients underwent Beyond cold light tooth whitening between February 2009 and July 2014. The effect of treatment was evaluated by Vitapan Classical shade guide. The percentage of discolored teeth that could not be matched by the aforementioned shade guide was calculated. By contrast, the color difference between discolored teeth and corresponding shade tabs was calculated for discolored teeth that could be matched by the shade guide. RESULTS: Approximately 64% (16/25) of tetracycline teeth and 28% (17/61) of mottled-enamel teeth could not be matched using the Vitapan Classical shade guide, but yellow teeth were all matched, and the difference between any pair of teeth was statistically significant (P=0.000). For discolored teeth that could be matched, statistically significant difference was found in the DeltaL*, Deltab*, and DeltaE between tetracycline and yellow teeth, as well as between tetracycline and mottled-enamel teeth. However, no statistically significant difference was found between mottled enamel and yellow teeth. Moreover, no statistically significant difference was found in the Deltaa* among the three groups. CONCLUSION: Vitapan Classical shade guide could not be used to evaluate effectively the effect of tooth whitening, especially for tetracycline and mottled-enamel teeth. The evaluating method should be improved. PMID- 26552243 TI - [Sustained negative pressure drainage for treatment of severe maxillofacial and neck space infection]. AB - OBJECTIVE: This study observed the curative effect of sustained negative pressure drainage application on treatment of severe maxillofacial and neck space infection. METHODS: Incision and drainage were performed to treat 18 patients with severe maxillofacial and neck space infection. A small incision was made on the site of the most obvious swelling or fluctuations, and localized negative pressure was applied with a drainage device on the wound during suturing. RESULTS: Among the 18 patients, 14 were healed, whereas 4 underwent dehiscence of the wound after the operation. Negative pressure was lost as the drainage tubes were removed, and non-negative pressure drainage method was used instead. During the negative pressure treatment, swelling and pain did not increase after the operation. Other complications, such as asphyxia, septic shock, or mediastinal abscess, did not occur. All the patients were healed and eventually discharged from the hospital. CONCLUSION: Sustained negative pressure drainage, which is a modified version of the traditional method of incision and drainage, is an alternative treatment for severe maxillofacial and neck space infection. Such treatment reduces patient pain and eases doctor exertion. Thus, this method provides a new therapeutic strategy for severe maxillofacial and neck space infection. PMID- 26552244 TI - [Correlation analysis of the nasolabial angle of Angle's Class II division 1 malocclusion patients with vertical growth pattern after tooth extraction orthodontic treatment]. AB - OBJECTIVE: This study aims to evaluate the nasolabial angle change and the correlation analysis ot Angle'Is Class II division 1 malocclusion patients with vertical growth pattern after tooth extraction orthodontic treatment and provide experimental results to help in making orthodontic treatment plan and treatments. METHODS: A total of 38 Angle's Class II division 1 malocclusion patients with vertical growth pattern and tooth extraction orthodontic treatment were included in this study. Pre- and post-treatment cephalometric X-rays were performed, and 18 measurement items were measured. The change values of pre- and post-treatment, youngsters, and adults were compared to analyze the correlation of the nasolabial angle change. RESULTS: The nasolabial angle between youngsters and adults was enlarged after treatment, but the nasolabial angle of the adult group changed more significantly. Ul to FH, Ul to NA, U1-NA, Spr-Ptm were reduced after treatment, and the adult group decreased more significantly. The upper lip sulcus and flange thickness, A'-Ptm, upper lip length, and nose prominence were enlarged after the adolescent treatment, but the adult had a certain degree of decrease. The difference had statistical significance. In the correlation of the nasolabial angle change analysis of the two groups, namely, Ul to FH, Ul-NA and U1 to NA had significant negative correlation, significant positive correlation to the upper lip inclination angle, and more significant correlation in the adult group. Upper lip flange thickness and nasolabial angle were negatively correlated, and the upper lip sulcus thickness was positively correlated. However, no significant correlation was observed between these two in the adult group. CONCLUSION: The nasolabial angle change of adolescents with vertical growth pattern in class II division 1 malocclusion after extraction treatment is related to the upper anterior teeth hard tissue and upper lip soft tissue, whereas only adults and upper anterior teeth hard tissue are related. PMID- 26552245 TI - [Study on the effect of different impression methods on the marginal fit of all ceramic crowns]. AB - OBJECTIVE: To investigate the effect of three different impression methods on the marginal fit of all-ceramic crowns. The three methods include scanning silicone rubber impression, cast models, and direct optical impression. METHODS: The polymethyl methacrylate (PMMA) material of a mandibular first molar in standard model was prepared with 16 models duplicated. The all-ceramic crowns were prepared using three different impression methods. Accurate impressions were made using silicone rubber, and the cast models were obtained. The PMMA models, silicone rubber impressions, and cast models were scanned, and digital models of three groups were obtained to produce 48 zirconia all-ceramic crowns with computer aided design/computer aided manufacture. The marginal fit of these groups was measured by silicone rubber gap impression. Statistical analysis was performed with SPSS 17.0 software. RESULTS: The marginal fit of direct optical impression groups, silicone rubber impression groups, cast model groups was (69.18+/-9.47), (81.04+/-10.88), (84.42+/-9.96) um. A significant difference was observed in the marginal fit of the direct optical impression groups and the other groups (P<0.05). No statistically significant difference was observed in the marginal fit of the silicone rubber impression groups and the cast model groups (P>0.05). CONCLUSION: All marginal measurement sites are clinically acceptable by the three different impression scanning methods. The silicone rubber impression scanning method can be used for all-ceramic restorations. PMID- 26552246 TI - [Long-term follow-up study of titanium implant impact on pediatric mandibular growth and development]. AB - OBJECTIVE: To explore the impact of titanium implant on the growth and development of pediatric mandible after suffering from mandibular fracture and undergoing open reduction and internal fixation (ORIF) compared with those that underwent titanium plate removal postoperatively. METHODS: Fifteen pediatric patients with mandibular fracture who underwent ORIF were included in this study. Eight patients did not undergo titanium implant removal postoperatively, whereas the other seven patients underwent the routine. The postoperative data of the pediatrics were collected for comparative analysis by taking the patients' frontal and lateral photos, recording the inter-incisor distance, and measuring the height of mandibular ramus, length of the mandibular body, and combined length of the mandible in three-dimensional reconstruction image. RESULTS: All patients had acceptable facial contour, mouth opening, and occlusion, without obvious abnormalities. The radiography showed no significant difference between the bilateral mandibular lengths in the two groups of patients (P>0.05). CONCLUSION: The titanium plants have no significant impact on the growth and development of pediatric mandible postoperatively; hence, the question on whether the titanium plates should be removed or not may be neglected. The removal operation may lead to secondary trauma; thus, performing titanium plate removal routinely is not recommended. PMID- 26552247 TI - [Application of anterolateral thigh myocutaneous flap using computed tomography angiography for mouth-floor reconstruction after resection of middle-late stage carcinoma of mouth floor]. AB - OBJECTIVE: The aim of this study was to investigate the value of free anterolateral thigh myocutaneous flap (ALTMF) and computed tomography angiography (CTA) for the reconstruction of mouth-floor defects after the resection of middle late stage carcinoma of the mouth floor. METHODS: Sixteen cases of middle-late stage carcinomas of the mouth floor underwent radical resection, and mouth-floor and tongue defects were reconstructed with ALTMF. CTA was applied to plan the lateral circumflex femoral artery (LCFA) and its perforating vessel, which was verified during the operation. RESULTS: The position of the perforating vessel in the operation was fully consistent with that designed by the preoperative CTA. All 16 flaps completely survived. The appearance and function of all cases were both satisfactory. All donor sites were primarily closed and healed without functional morbidity. During the follow-up period of 6-36 months, 15 cases survived with acceptable aesthetic and functional results in mouth floor and tongue reconstruction, except for 1 case (T4N2M0) that died of metastasis carcinoma 10 months after operation. CONCLUSION: CTA can accurately locate the LCFA and artery perforator. Preoperative perforator planning using CTA in ALTMF transplantation is a reliable and useful method thatresults in safe operation with optimal outcome. The ALTMF is an ideal choice for the reconstruction of soft tissue defects after the resection of middle-late staie carcinoma of the mouth floor PMID- 26552248 TI - [Rare parotid gland tumors: enhanced computed tomography and pathological correlation]. AB - OBJECTIVE: To investigate the correlation between enhanced computed tomography (CT) findings and pathological results of rare parotid gland tumors, and improve diagnosis accuracy. METHODS: The enhanced CT manifestations of 22 cases with pathologically documented rare parotid gland tumors, which included 6 cases of basal cell tumor, 5 cases of myoepithelioma, 4 cases of vascular invasion, 3 cases of lymphatic cyst, 3 cases of lipoma, and 1 case of chondrosarcoma, were retrospectively analyzed. The location, size, shape, density, and relationship with surrounding structure were evaluated on CT images. RESULTS: The enhanced CT showed that basal cell tumors occurred in the superficial lobe of the parotid gland, with clear boundary, within the cystic lesion. The lesions were moderate to obviously enhanced, which may be accompanied by enlarged lymph nodes. Myoepithelial tumors were located in the superficial lobe of the parotid gland, with a small cystic prone and microcalcification within a few cases. The lesions were moderate to obviously enhanced. Hemangiomas of soft tissue mass prominent in the parotid gland surface were mild to significantly enhanced. Larger lesions may occupy the entire parotid gland, with uneven density and visible vein stone. The CT density values of the lymphatic cyst were usually higher. Chondrosarcoma mainly manifested cystic mass at the calcification edge. Lipoma with fat density mass exhibited clear boundary without enhancement. Fiber separation could be observed in the lesion. CONCLUSION: CT can reflect the pathological features of rare parotid gland tumors by demonstrating their corresponding imaging features. Enhanced CT is the most effective means of imaging to identify the nature of rare tumor of the parotid gland lesions. PMID- 26552249 TI - [Analysis of clinical and imaging findings in cementoblastoma]. AB - OBJECTIVE: To assess the clinical and imaging features of cementoblastoma for diagnosis and differential diagnosis. METHODS: Clinical and imaging data of 14 cases were selected for this retrospective study. RESULTS: A total of 14 cases of cementoblastoma patients with ages at diagnosis ranging from 11 years to 58 years (mean age, 27.6 years; median age, 21.0 years). The tumor affected 7 patients from each gender. The mandible was the main site of occurrence. The most common complaints were swelling and pain. Radiographic results showed that cementoblastoma typically presented as a well-circumscribed and radiopaque mass confluent with the involved tooth root and surrounded by a thin and uniform radio lucent border. Tumor parenchyma was generally mixed-density, which could be divided into two types, namely, homogeneous and heterogeneous patterns. Other significant imaging features included the periphery bone of the lesion sclerosis and cortical thickening of the lower edge of the mandible. CONCLUSION: Obvious characteristics are found in the clinical and imaging findings of cementoblastoma. Accurate recognition of this lesion is significant in clinic to avoid misdiagnoses. PMID- 26552250 TI - [Systematic review of magnetic resonance imaging in diagnosing mandibular invasion caused by oral cancers]. AB - OBJECTIVE: To evaluate the diagnostic value of magnetic resonance (MR) imaging in the diagnosis of mandibular invasion caused by oral cancers. METHODS: Medline, EMBASE, SIGLE, and Chinese biomedical literature database were searched electronically. Manual searching for 19 relevant Chinese journals was also performed. Two reviewers evaluated the literature and extracted the data. Meta Disc 1.4 was chosen to conduct the sensitivity (SEN), specificity (SPE), and 95% confidence interval (95%CI). RESULTS: Twelve studies with a total of 476 patients, namely, 5 prospective studies and 7 retrospective studies, were included. All the studies had unclear risk of bias. Meta-analysis result showed that the combination of SEN of MR in diagnosing mandibular invasion was 0.779 (95%CI: 0.719-0.831), combination of SPE was 0.823 (95%CI: 0.767-0.870), positive likelihood ratio was 3.442 (95%CI: 2.181-5.431), negative likelihood ratio was 0.286 (95%CI: 0.181- 0.451), and diagnostic odds ratio was 25.702 (95%CI: 13.406 49.273). The area under curve was 0.903 9 and Q* was 0.835 4. Meta-analysis was not processed when diagnosing mandibular medullary invasion because only two studies with 55 patients had been reported. The SEN was 0.838, and the SPE was 0.722. CONCLUSION: MR is efficient and has clinical value in the diagnosis of mandibular invasion caused by oral cancer. PMID- 26552251 TI - [Relation between obesity and oral health]. AB - Non-communicable diseases (NCDs) are important diseases that affect human health. Obesity is one of the major biological risk factors of NCDs. With the growing national economy and the increasing standard of living, the obesity problem is highlighted and could raise even more attention. Oral health is vital to overall health. To gain more recognition and popularize the monitoring of obesity in dentistry, this paper illustrates the status of present studies between obesity and oral health. PMID- 26552252 TI - [Diagnosis and management of intraparotid facial nerve schwannoma]. AB - Intraparotid facial nerve schwannoma (IFNS) is a rare benign tumor. The management of IFNS is very challenging because of the lack of appropriate methods for preoperative diagnosis, which is often conducted intraoperatively in most cases. This article reviewed the literature on IFNS recorded in PubMed from 1958 to 2014 and described in detail its clinical manifestations, diagnoses and differential diagnoses, and treatment options. Accurate diagnosis for IFNS mainly depends on intraoperative observation and postoperative histological examination. Preoperative facial nerve function, localization, and adherence, as well as preferences of IFNS patients are important factors to consider in the decision making process for IFNS management to optimize the outcomes. Surgical resection is usually reserved for patients with facial function of House-Brackmann grade III or worse; otherwise, conservative treatment can be adopted. PMID- 26552253 TI - [Garre's osteomyelitis with bilateral mandible: a case report]. AB - Garres osteomyelitis is a specific type of chronic osteomyelitis that most commonly occurs in young patients, secondary to dental infection, and affects the unilateral side of the mandible. Bilateral mandibular Garre's osteomyelitis is rare. In this article, a case of Garre's osteomyelitis with bilateral mandible is reported. Its etiology, clinical pathologic features, diagnosis, differential diagnosis, and treatment methods are discussed by reviewing relevant literature. PMID- 26552254 TI - [Giant benign symmetric lipomatosis of the neck: four case reports]. AB - Benign symmetric lipomatosis is a rare disease and may appear as a huge tumor in the neck. Four benign symmetric lipomatosis associated with gigantic painless mass or neck motion limitation were reported. Operative technique of one-time radical resection or stage resection was used to remove these tumors. One patient had a postoperative complication of incision effusion and infection, and three patients had no significant complication. At more than one-year follow-up, the motion and appearance of a patient's neck returned to normal, and no recurrence was observed. The etiology, clinical manifestations, diagnosis, and treatment of the disease were discussed. PMID- 26552255 TI - A conceptual framework to describe the ecology of fragmented landscapes and implications for conservation and management. AB - The study of the ecology of fragmented landscapes has been dominated by two assumptions: the unique unidirectional path from larger to smaller fragments and the negligible role of fragment species on fragment properties. An accurate conceptualization of fragmented landscapes requires consideration of the age and origin of the fragments, i.e., direct fragmentation or reverse fragmentation (generation or increase of vegetated fragments by colonization), and the habitat modifications of fragment species (autogenic processes). Colonization and autogenic processes alter the fragments' composition and function. Fragment metrics affect colonization. Autogenic processes are antagonized by disturbances and modulated by abiotic inputs. Fragment alterations by autogenic processes may explain the continuous species substitution detected in some fragments or the species persistence in others. Reverse fragmentation, a natural process in commonly disturbed landscapes, challenges the avoidance-of-habitat disturbance as the ultimate strategy for biodiversity conservation and stresses the importance of pioneer species that promote succession as resilience elements in fragmented landscapes. Among-fragment diversity, generated by local disturbances, can be essential for the resilience of fragmented landscapes, suggesting that conservation and habitat utilization can be complementary processes. Traditional agroforestry systems that depend on disturbance, fragmentation, colonization, and autogenic processes may provide important insights into fragmentation ecology. PMID- 26552256 TI - Can we infer plant facilitation from remote sensing? a test across global drylands. AB - Facilitation is a major force shaping the structure and diversity of plant communities in terrestrial ecosystems. Detecting positive plant-plant interactions relies on the combination of field experimentation and the demonstration of spatial association between neighboring plants. This has often restricted the study of facilitation to particular sites, limiting the development of systematic assessments of facilitation over regional and global scales. Here we explore whether the frequency of plant spatial associations detected from high-resolution remotely sensed images can be used to infer plant facilitation at the community level in drylands around the globe. We correlated the information from remotely sensed images freely available through Google Earth with detailed field assessments, and used a simple individual-based model to generate patch-size distributions using different assumptions about the type and strength of plant-plant interactions. Most of the patterns found from the remotely sensed images were more right skewed than the patterns from the null model simulating a random distribution. This suggests that the plants in the studied drylands show stronger spatial clustering than expected by chance. We found that positive plant co-occurrence, as measured in the field, was significantly related to the skewness of vegetation patch-size distribution measured using Google Earth images. Our findings suggest that the relative frequency of facilitation may be inferred from spatial pattern signals measured from remotely sensed images, since facilitation often determines positive co occurrence among neighboring plants. They pave the road for a systematic global assessment of the role of facilitation in terrestrial ecosystems. PMID- 26552257 TI - Quantifying ecosystem quality by modeling multi-attribute expert opinion. AB - The evaluation of ecosystem quality is inherently subjective, requiring decisions about which variables to notice or measure, and how these variables are integrated into a coherent evaluation. Despite the central role of human judgment, few evaluation methods address the subjectivity that is inherent in their design. There are, however, advantages to directly using opinion to create an expert system where the metric is constructed around opinion data. These advantages include stakeholder inclusion and the encouragement of a dialogue of data-driven criticism rather than subjective counter-opinion. We create an expert system to express the quality of a grassland ecosystem in Australia. We use an ensemble of bagged regression trees trained on calibrated expert preference data, to model the perceived quality of this grassland using a set of eight site variables as inputs. The model provides useful predictions of grassland quality, producing predictions similar to real expert evaluations of independent synthetic test sites not used to train the model. We apply the model to real grassland sites ranging from pristine to highly degraded, and confirm that our model orders the sites according to their degree of modification. We demonstrate that the use of too few experts produces relatively poor results, and show that for our problem the use of data from over twenty experts is appropriate. The scaling approach we used to calibrate between-expert data is shown to be an appropriate mechanism for aggregating the opinions of multiple experts. The resultant model will be useful in many contexts, and can be used by managers as a tool to evaluate real sites. It can also be integrated into ecological models of change as a means of evaluating predicted changes, for example, as a measure of utility when combined with cost estimates. The basic approach demonstrated here is applicable to any ecosystem, and we discuss the opportunities and limitations of its wider use. PMID- 26552258 TI - Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression. AB - Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-process feedback between vegetation and fire exist, they have been geographically limited or did not consider the influence of time between fires and weather. The availability of remotely sensed data identifying fire activity over the last four decades provides an opportunity to explicitly quantify-the ability of wildland fire to limit the progression of subsequent fire. Furthermore, advances in fire progression mapping now allow an evaluation of how daily weather as a top-down control modifies this effect. In this study, we evaluated the ability of wildland fire to create barriers that limit the spread of subsequent fire along a gradient representing time between fires in four large study areas in the western United States. Using fire progression maps in conjunction with weather station data, we also evaluated the influence of daily weather. Results indicate that wildland fire does limit subsequent fire spread in all four study areas, but this effect decays over time; wildland fire no longer limits subsequent fire spread 6-18 years after fire, depending on the study area. We also found that the ability of fire to regulate, subsequent fire progression was substantially reduced under extreme conditions compared to moderate weather conditions in all four study areas. This study increases understanding of the spatial feedbacks that can lead to self-regulating landscapes as well as the effects of top-down controls, such as weather, on these feedbacks. Our results will be useful to managers who seek to restore natural fire regimes or to exploit recent burns when managing fire. PMID- 26552259 TI - Landscape fragmentation, severe drought, and the new Amazon forest fire regime. AB - Changes in weather and land use are transforming the spatial and temporal characteristics of fire regimes in Amazonia, with important effects on the functioning of dense (i.e., closed-canopy), open-canopy, and transitional forests across the Basin. To quantify, document, and describe the characteristics and recent changes in forest fire regimes, we sampled 6 million ha of these three representative forests of the eastern and southern edges of the Amazon using 24 years (1983-2007) of satellite-derived annual forest fire scar maps and 16 years of monthly hot pixel information (1992-2007). Our results reveal that changes in forest fire regime properties differentially affected these three forest types in terms of area burned and fire scar size, frequency, and seasonality. During the study period, forest fires burned 15% (0.3 million ha), 44% (1 million ha), and 46% (0.6 million ha) of dense, open, and transitional forests, respectively. Total forest area burned and fire scar size tended to increase over time (even in years of average rainfall in open canopy and transitional forests). In dense forests, most of the temporal variability in fire regime properties was linked to El Nino Southern Oscillation (ENSO)-related droughts. Compared with dense forests, transitional and open forests experienced fires twice as frequently, with at least 20% of these forests' areas burning two or more times during the 24 year study period. Open and transitional forests also experienced higher deforestation rates than dense forests. During drier years, the end of the dry season was delayed by about a month, which resulted in larger burn scars and increases in overall area burned later in the season. These observations suggest that climate-mediated forest flammability is enhanced by landscape fragmentation caused by deforestation, as observed for open and transitional forests in the Eastern portion of the Amazon Basin. PMID- 26552260 TI - The consequences of photoperiodism for organisms in new climates. AB - A change in climate is known to affect seasonal timing (phenology) of the life stages of poikilothermic organisms whose development depends on temperature. Less understood is the potential for even greater disruption to the life cycle when a phenology shift exposes photoperiod-sensitive life stages to new day lengths. We present a conceptual framework and model to investigate the ways that photoperiod cued diapause can interact with a change in climate or latitude to influence voltinism in poikilothermic organisms. Our degree-day phenology model combines detailed spatial climate data, latitude- and date-specific photoperiods, and development and photoperiod response parameters. As an example, we model the biological control beetle Galerucella calmariensis and map the number of generations expected following its introduction into diverse climates throughout the continental United States. Incorporation of photoperiodism results in a complex geography of voltinism that differs markedly from predictions of traditional phenology models. Facultative multivoltine species will be prone to univoltism when transported to either warmer or southern climates due to exposure of the sensitive stage to shorter day lengths. When moved to more northern locations, they may attempt too many generations for the season duration thereby exposing vulnerable life stages to harsh weather in the fall. We further show that even small changes in temperature can result in large and unexpected shifts in voltinism. Analogous effects may be expected for organisms from wide variety of taxa that use photoperiod as a seasonal cue during some stage of their life cycle. Our approach is useful for understanding the performance and impacts of introduced pests and beneficial organisms as well as for predicting responses of resident species to climate change and climate variability. PMID- 26552261 TI - Modeling with uncertain science: estimating mitigation credits from abating lead poisoning in Golden Eagles. AB - Challenges arise when renewable energy development triggers "no net loss" policies for protected species, such as where wind energy facilities affect Golden Eagles in the western United States. When established mitigation approaches are insufficient to fully avoid or offset losses, conservation goals may still be achievable through experimental implementation of unproven mitigation methods provided they are analyzed within a framework that deals transparently and rigorously with uncertainty. We developed an approach to quantify and analyze compensatory mitigation that (1) relies on expert opinion elicited in a thoughtful and structured process to design the analysis (models) and supplement available data, (2) builds computational models as hypotheses about cause-effect relationships, (3) represents scientific uncertainty in stochastic model simulations, (4) provides probabilistic predictions of "relative" mortality with and without mitigation, (5) presents results in clear formats useful to applying risk management preferences (regulatory standards) and selecting strategies and levels of mitigation for immediate action, and (6) defines predictive parameters in units that could be monitored effectively, to support experimental adaptive management and reduction in uncertainty. We illustrate the approach with a case study characterized by high uncertainty about underlying biological processes and high conservation interest: estimating the quantitative effects of voluntary strategies to abate lead poisoning in Golden Eagles in Wyoming due to ingestion of spent game hunting ammunition. PMID- 26552262 TI - The differential effects of increasing frequency and magnitude of extreme events on coral populations. AB - Extreme events, which have profound ecological consequences, are changing in both frequency and magnitude with climate change. Because extreme temperatures induce coral bleaching, we can explore the relative impacts of changes in frequency and magnitude of high temperature events on coral reefs. Here, we combined climate projections and a dynamic population model to determine how changing bleaching regimes influence coral persistence. We additionally explored how coral traits and competition with macroalgae mediate changes in bleaching regimes. Our results predict that severe bleaching events reduce coral persistence more than frequent bleaching. Corals with low adult mortality and high growth rates are successful when bleaching is mild, but bleaching resistance is necessary to persist when bleaching is severe, regardless of frequency. The existence of macroalgae dominated stable states reduces coral persistence and changes the relative importance of coral traits. Building on previous studies, our results predict that management efforts may need to prioritize protection of "weaker" corals with high adult mortality when bleaching is mild, and protection of "stronger" corals with high bleaching resistance when bleaching is severe. In summary, future reef projections and conservation targets depend on both local bleaching regimes and biodiversity. PMID- 26552263 TI - Population dynamics of a northern-adapted mammal: disentangling the influence of predation and climate change. AB - Community structure and interspecific interactions are particularly vulnerable to rapidly changing climatic regimes. Recent changes in both climate and vertebrate community assemblages have created a unique opportunity to examine the impacts of two dynamic forces on population regulation. We examined the effects of warming winter conditions and the reestablishment of a previously extirpated predator, the fisher (Martes pennanti), on regulatory mechanisms in a northern-adapted mammal, the porcupine (Erethizon dorsatum), along their southern range boundary. Using a long-term (17-year) capture-recapture data set, we (1) quantified the impacts of climate change and increased fisher predation on the survival of adult porcupines at their regional southern terminus, (2) assessed recruitment (via both adult fecundity and juvenile survival) of porcupines, and (3) modeled the relative importance of predation and winter conditions on the demography and population growth rate (lambda). Severe winters and abundant predators interacted synergistically to reduce adult survivorship by as much as 44%, while expanding predator populations led to near reproductive failure among porcupines. Increasing predatory pressure, disruptions in this community module, and more frequent extreme winter weather events led to predicted extirpation within 50 years, whereas in the absence of predators, the population was viable. Our results provide a mechanistic understanding behind distributional shifts resulting from climate change and may be broadly relevant for predicting future distributional shifts in other northern-adapted mammalian species. PMID- 26552264 TI - Habitat restoration promotes pollinator persistence and colonization in intensively managed agriculture. AB - Widespread evidence of pollinator declines has led to policies supporting habitat restoration including in agricultural landscapes. Yet, little is yet known about the effectiveness of these restoration techniques for promoting stable populations and communities of pollinators, especially in intensively managed agricultural landscapes. Introducing floral resources, such as flowering hedgerows, to enhance intensively cultivated agricultural landscapes is known to increase the abundances of native insect pollinators in and around restored areas. Whether this is a result of local short-term concentration at flowers or indicative of true increases in the persistence and species richness of these communities remains unclear. It is also unknown whether this practice supports species of conservation concern (e.g., those with more specialized dietary requirements). Analyzing occupancies of native bees and syrphid flies from 330 surveys across 15 sites over eight years, we found that hedgerow restoration promotes rates of between-season persistence and colonization as compared with unrestored field edges. Enhanced persistence and colonization, in turn, led to the formation of more species-rich communities. We also find that hedgerows benefit floral resource specialists more than generalists, emphasizing the value of this restoration technique for conservation in agricultural landscapes. PMID- 26552265 TI - Effective time closures: quantifying the conservation benefits of input control for the Pacific chub mackerel fishery. AB - Restricting human access to a specific wildlife species, community, or ecosystem, i.e., input control, is one of the most popular tools to control human impacts for natural resource management and wildlife conservation. However, quantitative evaluations of input control are generally difficult, because it is unclear how much human impacts can actually be reduced by the control. We present a model framework to quantify the effectiveness of input control using day closures to reduce actual fishing impact by considering the observed fishery dynamics. The model framework was applied to the management of the Pacific stock of the chub mackerel (Scomber japonicus) fishery, in which fishing was suspended for one day following any day when the total mackerel catch exceeded a threshold level. We evaluated the management measure according to the following steps: (1) we fitted the daily observed catch and fishing effort data to a generalized linear model (GLM) or generalized autoregressive state-space model (GASSM), (2) we conducted population dynamics simulations based on annual catches randomly generated from the parameters estimated in the first step, (3) we quantified the effectiveness of day closures by comparing the results of two simulation scenarios with and without day closures, and (4) we conducted additional simulations based on different sets of explanatory variables and statistical models (sensitivity analysis). In the first step, we found that the GASSM explained the observed data far better than the simple GLM. The model parameterized with the estimates from the GASSM demonstrated that the day closures implemented from 2004 to 2009 would have decreased exploitation fractions by ~10% every year and increased the 2009 stock biomass by 37-46% (median), relative to the values without day closures. The sensitivity analysis revealed that the effectiveness of day closures was particularly influenced by autoregressive processes in the fishery data and by positive relationships between fishing effort and total biomass. Those results indicated the importance of human behavioral dynamics under input control in quantifying the conservation benefit of natural resource management and the applicability of our model framework to the evaluation of the input controls that are actually implemented. PMID- 26552266 TI - Insecticides promote viral outbreaks by altering herbivore competition. AB - While the management of biological invasions is often characterized by a series of single-specieg decisions, invasive species exist within larger food webs. These biotic interactions can alter the impact of control/eradication programs and may cause suppression efforts to inadvertently facilitate invasion spread and impact. We document the rapid replacement of the invasive Bemisia Middle East Asia Minor I (MEAM1) cryptic biotype by the cryptic Mediterranean (MED) biotype throughout China and demonstrate that MED is more tolerant of insecticides and a better vector of tomato yellow leaf curl virus (TYLCV) than MEAMJ. While MEAM1 usually excludes MED under natural conditions, insecticide application reverses the MEAM1-MED competitive hierarchy and allows MED to exclude MEAMI. The insecticide-mediated success of MED has led to TYLCV outbreaks throughout China. Our work strongly supports the hypothesis that insecticide use in China reverses the MEAMl-MED competitive hierarchy and allows MED to displace MEAM1 in managed landscapes. By promoting the dominance of a Bemisia species that is a competent viral vector, insecticides thus increase the spread and impact of TYLCV in heterogeneous agroecosystems. PMID- 26552267 TI - Predator identity influences the effect of habitat management on nest predation. AB - Predation is the leading cause of nest failure for many passerines and considerable effort is devoted to identifying the habitat characteristics and management practices that influence nest loss. The habitat components associated with nest loss are strongly influenced by the ecology of nest predators and differ among predator species as a result. Nevertheless, there is a tendency to generalize about the effects of habitat features and management on nest failure without considering how resulting patterns are influenced by nest predators. We examined how predator-specific patterns of nest loss differed among predators and in response to grassland management with fire and grazing by cattle (Bos taurus). We used video cameras to monitor and identify predators at nests of the Grasshopper Sparrow (Ammodramus savannarum), a species of conservation concern throughout its range. We observed predation by 15 different species that differed in their response to management and the habitat characteristics associated with nests they preyed on. Losses to mammals and snakes were more likely at nests with greater amounts of litter cover and tall fescue (Schedonorus phoenix). Mammals were less likely to prey on nests surrounded by greater forb cover. Nest predation by snakes was lower in burned areas, whereas predation by mammals and Brown-headed Cowbirds (Molothrus ater) was unaffected by the use of fire. Neither vegetation density at the nest, nor landscape context was related to nest loss by any predator taxon. Although there were many similarities, we identified important differences in the species composing the nest predator community between our. study and other published research. These differences are likely to be responsible for geographic variation in the influence of habitat features and management actions on nest success. Our results demonstrate the need for natural resource managers to incorporate knowledge of local nest predators and their ecology when developing management prescriptions aimed at enhancing the reproductive success of songbirds. PMID- 26552268 TI - Combined effects of climate, predation, and density dependence on Greater and Lesser Scaup population dynamics. AB - An understanding of species relationships is critical in the management and conservation of populations facing climate change, yet few studies address how climate alters species interactions and other population drivers. We use a long term, broad-scale data set of relative abundance to examine the influence of climate, predators, and density dependence on the population dynamics of declining scaup (Aythya) species within the core of their breeding range. The state-space modeling approach we use applies to a wide range of wildlife species, especially populations monitored over broad spatiotemporal extents. Using this approach, we found that immediate snow cover extent in the preceding winter and spring had the strongest effects, with increases in mean snow cover extent having a positive effect on the local surveyed abundance of scaup. The direct effects of mesopredator abundance on scaup population dynamics were weaker, but the results still indicated a potentil interactive process between climate and food web dynamics (mesopredators, alternative prey, and scaup). By considering climate variables and other potential effects on population dynamics, and using a rigorous estimation framework, we provide insight into complex ecological processes for guiding. conservation and policy actions aimed at mitigating and reversing the decline of scaup. PMID- 26552269 TI - Accuracy of nonmolecular identification of growth-hormone- transgenic coho salmon after simulated escape. AB - Concerns with transgenic animals include the potential ecological risks associated with release or escape to the natural environment, and a critical requirement for assessment of ecological effects is the ability to distinguish transgenic animals from wild type. Here, we explore geometric morphometrics (GeoM) and human expertise to distinguish growth-hormone-transgenic coho salmon (Oncorhynchus kisutch) specimens from wild type. First, we simulated an escape of 3-month-old hatchery-reared wild-type and transgenic fish to an artificial stream, and recaptured them at the time of seaward migration at an age of 13 months. Second, we reared fish in the stream from first-feeding fry until an age of 13 months, thereby simulating fish arising from a successful spawn in the wild of an escaped hatchery-reared transgenic fish. All fish were then assessed from 'photographs by visual identification (VID) by local staff and by GeoM based on 13 morphological landmarks. A leave-one-out discriminant analysis of GeoM data had on average 86% (72-100% for individual groups) accuracy in assigning the correct genotypes, whereas the human experts were correct, on average, in only 49% of cases (range of 18-100% for individual fish groups). However, serious errors (i.e., classifying transgenic specimens as wild type) occurred for 7% (GeoM) and 67% (VID) of transgenic fish, and all of these incorrect assignments arose with fish reared in the stream from the first-feeding stage. The results show that we presently lack the skills of visually distinguishing transgenic coho salmon from wild type with a high level of accuracy, but that further development of GeoM methods could be useful in identifying second-generation,fish from nature as a nonmolecular approach. PMID- 26552270 TI - Combining near infrared spectra of feces and geostatistics to generate forage nutritional quality maps across landscapes. AB - An important asset for the management of wild ungulates is recognizing the spatial distribution of forage quality across heterogeneous landscapes. To do so typically requires knowledge of which plant species are eaten, in what abundance they are eaten, and what their nutritional quality might be. Acquiring such data, however, may be difficult and time consuming. Here, we are proposing a rapid and cost-effective forage quality monitoring tool that combines near infrared (NIR) spectra of fecal samples and easily obtained data on plant community composition. Our approach rests on the premise that NIR spectra of fecal samples collected within low population density exclosures reflect the optimal forage quality of a given landscape. Forage quality can thus be based on the Mahalanobis distance of fecal spectral scans across the landscape relative to fecal spectral scans inside exclosures (referred to as DISTEX). The Gi* spatial autocorrelation statistic can then be applied among neighboring DISTEX values to detect and map "hot spots" and "cold spots" of nutritional quality over the landscape. We tested our approach in a heterogeneous boreal landscape on Anticosti Island (Quebec, Canada), where white-tailed deer (Odocoileus virginianus) populations over the landscape have ranged from 20 to 50 individuals/km2 for at least 80 years, resulting in a loss of most palatable and nutritious plant species. Our results suggest that hot spots of forage quality occur when old-growth balsam fir stands comprise >39.8% of 300 ha neighborhoods, whereas cold spots occur in laggs (i.e., transition zones from forest to peatland). In terms of ground-level indicator plant species, the presence of Canada bunchberry (Cornus canadensis) was highly correlated with hot spots, whereas tamarack (Larix laricina) was highly correlated with cold spots. Mean DISTEX values were positively and significantly correlated with the neutral detergent fiber and acid detergent lignin contents of feces. While our approach would need more independent field trials before it is fully validated, its low cost and ease of execution should make it a valuable tool for advancing both the basic and applied ecology of large herbivores. PMID- 26552271 TI - Modeling carbon-nutrient interactions during the early recovery of tundra after fire. AB - Fire frequency has dramatically increased in the tundra of northern Alaska, USA, which has major implications for the carbon budget of the region and the functioning of these ecosystems, which support important wildlife species. We investigated the postfire succession of plant and soil carbon (C), nitrogen (N), and phosphorus (P) fluxes and stocks along a burn severity gradient in the 2007 Anaktuvuk River fire scar in northern Alaska. Modeling results indicated that the early regrowth of postfire tundra vegetation was limited primarily by its canopy photosynthetic potential, rather than nutrient availability, because of the initially low leaf area and relatively high inorganic N and P concentrations in soil. Our simulations indicated that the postfire recovery of tundra vegetation was sustained predominantly by the uptake of residual inorganic N (i.e., in the remaining ash), and the redistribution of N and P from soil organic matter to vegetation. Although residual nutrients in ash were higher in the severe burn than the moderate burn, the moderate burn recovered faster because of the higher remaining biomass and consequent photosynthetic potential. Residual nutrients in ash allowed both burn sites to recover and exceed the unburned site in both aboveground biomass and production five years after the fire. The investigation of interactions among postfire C, N, and P cycles has contributed to a mechanistic understanding of the response of tundra ecosystems to fire disturbance. Our study provided insight on how the trajectory of recovery of tundra from wildfire is regulated during early succession. PMID- 26552272 TI - Climate-suitable planting as a strategy for maintaining forest productivity and functional diversity. AB - Within the time frame of the longevity of tree species, climate change will change faster than the ability of natural tree migration. Migration lags may result in reduced productivity and reduced diversity in forests under current management and climate change. We evaluated the efficacy of planting climate suitable tree species (CSP), those tree species with current or historic distributions immediately south of a focal landscape, to maintain or increase aboveground biomass productivity, and species and functional diversity. We modeled forest change with the LANDIS-II forest simulation model for 100 years (2000-2100) at a 2-ha cell resolution and five-year time steps within two landscapes in the Great Lakes region (northeastern Minnesota and northern lower Michigan, USA). We compared current climate to low- and high-emission futures. We simulated a low-emission climate future with the Intergovernmental Panel on Climate Change (IPCC) 2007 B1 emission scenario and the Parallel Climate Model Global Circulation Model (GCM). We simulated a high-emission climate future with the IPCC A1FI emission scenario and the Geophysical Fluid Dynamics Laboratory (GFDL) GCM. We compared current forest management practices (business-as-usual) to CSP management. In the CSP scenario, we simulated a target planting of 5.28% and 4.97% of forested area per five-year time step in the Minnesota and Michigan landscapes, respectively. We found that simulated CSP species successfully established in both landscapes under all climate scenarios. The presence of CSP species generally increased simulated aboveground biomass. Species diversity increased due to CSP; however, the effect on functional diversity was variable. Because the planted species were functionally similar to many native species, CSP did not result in a consistent increase nor decrease in functional diversity. These results provide an assessment of the potential efficacy and limitations of CSP management. These results have management implications for sites where diversity and productivity are expected to decline. Future efforts to restore a specific species or forest type may not be possible, but CSP may sustain a more general ecosystem service (e.g., aboveground biomass). PMID- 26552273 TI - Evaluating species richness: Biased ecological inference results from spatial heterogeneity in detection probabilities. AB - Accurate estimates of species richness are necessary to test predictions of ecological theory and evaluate biodiversity for conservation purposes. However, species richness is difficult to measure in the field because some species will almost always be overlooked due to their cryptic nature or the observer's failure to perceive their cues. Common measures of species richness that assume consistent observability across species are inviting because they may require only single counts of species at survey sites. Single-visit estimation methods ignore spatial and temporal variation in species detection probabilities related to survey or site conditions that may confound estimates of species richness. We used simulated and empirical data to evaluate the bias and precision of raw species counts, the limiting forms of jackknife and Chao estimators, and multispecies occupancy models when estimating species richness to evaluate whether the choice of estimator can affect inferences about the relationships between environmental conditions and community size under variable detection processes. Four simulated scenarios with realistic and variable detection processes were considered. Results of simulations indicated that (1) raw species counts were always biased low, (2) single-visit jackknife and Chao estimators were significantly biased regardless of detection process, (3) multispecies occupancy models were more precise and generally less biased than the jackknife and Chao estimators, and (4) spatial heterogeneity resulting from the effects of a site covariate on species detection probabilities had significant impacts on the inferred relationships between species richness and a spatially explicit environmental condition. For a real data set of bird observations in northwestern Alaska, USA, the four estimation methods produced different estimates of local species richness, which severely affected inferences about the effects of shrubs on local avian richness. Overall, our results indicate that neglecting the effects of site covariates on species detection probabilities may lead to significant bias in estimation of species richness, as well as the inferred relationships between community size and environmental covariates. PMID- 26552274 TI - Testing scale-dependent effects of seminatural habitats on farmland biodiversity. AB - The effectiveness of conservation interventions for maximizing biodiversity benefits from agri-environment schemes (AESs) is expected to depend on the quantity of seminatural habitats in the surrounding landscape. To verify this hypothesis, we developed a hierarchical sampling design to assess the effects of field boundary type and cover of seminatural habitats in the landscape at two nested spatial scales. We sampled three types of field boundaries with increasing structural complexity (grass margin, simple hedgerow, complex hedgerow) in paired landscapes with the presence or absence of seminatural habitats (radius 0.5 km), that in turn, were nested within 15 areas with different proportions of seminatural habitats at a larger spatial scale (10 X 10 km). Overall, 90 field boundaries were sampled across a Mediterranean'region (northeastern Italy). We considered species richness response across three different taxonomic groups: vascular plants, butterflies, and tachinid flies. No interactions between type of field boundary and surrounding landscape were found at either 0.5 and 10 km, indicating that the quality of field boundary had the same effect irrespective of the cover of seminatural habitats. At the local scale, extended-width grass margins yielded higher plant species richness, while hedgerows yielded higher species richness of butterflies and tachinids. At the 0.5-km landscape scale, the effect of the proportion of seminatural habitats was neutral for plants and tachinids, while butterflies were positively related to the proportion of forest. At the 10-km landscape scale, only butterflies responded positively to the proportion of seminatural habitats. Our study confirmed the importance of testing multiple scales when considering species from different taxa and with different mobility. We showed that the quality of field boundaries at the local scale was an important factor in enhancing farmland biodiversity. For butterflies, AESs should focus particular attention on preservation'of forest patches in agricultural landscapes within 0.5 kin, as well as the conservation of seminatural habitats at a wider landscape scale. PMID- 26552275 TI - Relating suborganismal processes to ecotoxicological and population level endpoints using a bioenergetic model. AB - Ecological effects of environmental stressors are commonly evaluated using organismal or suborganismal data, such as standardized toxicity tests that characterize responses of individuals (e.g., mortality and reproduction) and a rapidly growing body of "omics" data. A key challenge for environmental risk assessment is relating such information to population dynamics. One approach uses dynamic energy budget (DEB) models that relate growth and reproduction of individuals to underlying flows of energy and elemental matter. We hypothesize that suborganismal information identifies DEB parameters that are most likely impacted by a particular stressor and that the DEB model can then project suborganismal effects on life history and population endpoints. We formulate and parameterize a model of growth and reproduction for the water flea Daphnia magna. Our model resembles previous generic bioenergetic models, but has explicit representation of discrete molts, an important feature of Daphnia life history. We test its ability to predict six endpoints commonly used in chronic toxicity studies in specified food environments. With just one adjustable parameter, the model successfully predicts growth and reproduction of individuals from a wide array of experiments performed in multiple laboratories using different clones of D. magna raised on different food sources. Fecundity is the most sensitive endpoint, and there is broad correlation between the sensitivities of fecundity and long-run growth rate, as is desirable for the default metric used in chronic toxicity tests. Under some assumptions, we can combine our DEB model with the Euler-Lotka equation to estimate longrun population growth rates at different food levels. A review of Daphnia gene-expression experiments on the effects of contaminant exposure reveals several connections to model parameters, in particular a general trend of increased transcript expression of genes involved in energy assimilation and utilization at concentrations affecting growth and reproduction. The sensitivity of fecundity to many model parameters was consistent with frequent generalized observations of decreased expression of genes involved in reproductive physiology, but interpretation of these observations requires further mechanistic modeling. We thus propose an approach based on generic DEB models incorporating few essential species-specific features for rapid extrapolation of ecotoxicogenomic assays for Daphnia-based population risk assessment. PMID- 26552276 TI - Moderate land use changes plant functional composition without loss of functional diversity in India's Western Ghats. AB - The fields of ecology and conservation science increasingly recognize the importance of managing for functional composition and functional diversity to maintain critical ecosystem processes and services. However, little is known about the degree to which widespread but moderate forms of land use that maintain overall vegetation structure are compatible with the conservation of functional diversity. We assessed differences in plani functional composition and functional diversity across savanna woodlands in the Western Ghats, India, managed with varying degrees of biomass extraction, livestock grazing, and ground fire. Across the gradient of moderate land uses, we found shifts in functional composition but no overall decline in functional diversity with land, use intensification. Biomass extraction was associated with changes in dispersal mode, reduced seed mass, and lower overstory functional diversity. Livestock grazing was associated with shorter overstory species, reduced seed mass, and increased understory functional diversity. Nonnative invasive species contributed to shifts in understory functional composition with livestock grazing and increased functional diversity with more intensive land use. Our study highlights both the utility and some limitations of assessing conservation value with functional diversity. These results suggest that moderate-intensity local land use can be compatible with maintenance of functional diversity in savanna woodlands of the Western Ghats, and further efforts to maximize this compatibility would benefit conservation in South India's extensive human-managed landscapes. However, using functional diversity as the sole metric by which to gauge conservation value can mask threats from invasive species and loss of diversity within categories of biotic dispersal. Therefore, functional diversity metrics are likely to provide a valuable complement to, but not replacement for, other management targets such as species composition. PMID- 26552277 TI - Structure and composition of altered riparian forests in an agricultural Amazonian landscape. AB - Deforestation and fragmentation influence the microclimate, vegetation structure, and composition of remaining patches of tropical forest. In the southern Amazon, at the frontier of cropland expansion, forests are converted and fragmented in a pattern that leaves standing riparian forests whose dimensions are mandated by the Brazilian National Forest Code. These altered riparian forests share many characteristics of well-studied upland forest fragments, but differ because they remain connected to larger areas of forest downstream, and because they may experience wetter soil conditions because reduction of forest cover in the surrounding watershed raises groundwater levels and increases stream runoff. We compared forest regeneration, structure, composition, and diversity in four areas of intact riparian forest and four areas each of narrow, medium, and wide altered riparian forests that have been surrounded by agriculture since the early 1980s. We found that seedling abundance was reduced by as much as 64% and sapling abundance was reduced by as much as 67% in altered compared to intact riparian forests. The most pronounced differences between altered and intact forest occurred near forest edges and within the narrowest sections of altered riparian forests. Woody plant species composition differed and diversity was reduced in altered forests compared to intact riparian forests. However, despite being fragmented for several decades, large woody plant biomass and carbon storage, the number of live or dead large woody plants, mortality rates, and the size distribution of woody plants did not differ significantly between altered and intact riparian forests. Thus, even in these relatively narrow forests with high edge: area ratios, we saw no evidence of the increases in mortality and declines in biomass that have been found in other tropical forest fragment studies. However, because of the changes in both species community and reduced regeneration, it is unclear how long this relative lack of change will be sustained. Additionally, Brazil recently passed a law in their National Forest Code allowing narrower riparian buffers than those studied here in restored areas, which could affect their long-term sustainability. PMID- 26552278 TI - Biodiversity offsets are one solution to widespread poorly compensated biodiversity loss: a response to Curran et al.. PMID- 26552279 TI - The jury is still out on biodiversity offsets: reply to Quetier et al.. PMID- 26552280 TI - How do you feel about Medicaid Managed Care? PMID- 26552281 TI - Telemedicine Expanding in Arkansas Examples--UAMS and Beyond. PMID- 26552282 TI - Fontal Sinus Mucocele Manifests as Persistent Draining Abscess of Upper Eyelid. AB - Paranasal sinus mucocele and pyomucocele have a wide spectrum of symptomology and chronicity of clinical manifestations. We present a case of a 52-y/o previously healthy homeless male that presented with a 2-week history of a non-tender, persistently draining upper eyelid abscess, and 1-year history of nonspecific change of general appearance to his left eye. PMID- 26552283 TI - Quality Improvement is Unique in Arkansas Nursing Homes. PMID- 26552284 TI - Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8 Year-Old Child. AB - We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies. PMID- 26552286 TI - Looking forward. PMID- 26552285 TI - Budd-Chiari Syndrome in a patient with Multiple Hypercoagulopathies. AB - OBJECTIVE: To describe a patient with Budd-Chiari syndrome (BCS) found to have multiple hypercoagulopathies. CASE SUMMARY: A 33-year-old man who presented with abdominal distension, hematemesis, shortness of breath was found to have liver cirrhosis, portal hypertension and Budd-Chiari Syndrome. He was evaluated for hypercoagulability and was found to be heterozygous for Factor V Leiden mutation and his protein C level was 38% of normal. He was started on oral anticoagulation and underwent elective liver transplantation within 3 months of diagnosis. DISCUSSION: In patients with Budd-Chiari syndrome, factor V Leiden is the second most commonly identified prothrombotic state after primary myeloproliferative disorders. There may be a coexistence of several thrombophilic states in patients with Budd-Chiari Syndrome. CONCLUSIONS: Budd-Chiari syndrome is an uncommon disorder. Outcome is poor in many cases. Therefore, a successful diagnostic and therapeutic approach is of vital importance. A complete thrombophilia screening needs to be requested in all patients diagnosed with Budd-Chiari syndrome. Thorough investigation needs to be performed to identify an underlying process contributing to the hepatic venous outflow obstruction. PMID- 26552287 TI - Graduate of the first acute care surgery fellowship program reflects on the experience. PMID- 26552288 TI - Sharing clinical photographs: Patient rights, professional ethics, and institutional responsibilities. PMID- 26552289 TI - Advocacy and grassroots: Leveraging local issues at the national level. PMID- 26552290 TI - YFA Essay Contest winner: Promise of the profession: The chance to be human. PMID- 26552291 TI - The final rule on the Medicare Shared Savings Program. PMID- 26552292 TI - Improving access to surgical care in rural America: An interview with J. David Richardson. PMID- 26552293 TI - Improving resection rates in borderline resectable pancreatic cancer: Pilot study shows favorable results. PMID- 26552294 TI - ACS educational awards and MyCME. PMID- 26552295 TI - High reliability science and surgery: The Joint Commission's Robust Process Improvement methodology. PMID- 26552297 TI - ACS NSQIP conference: 10 years of putting the patient first. PMID- 26552296 TI - NTDB DATA POINTS: Fireworks. PMID- 26552298 TI - In memoriam: Dr. Norman McSwain, a pioneer in comprehensive trauma care. PMID- 26552299 TI - Thrombin modulates persistent sodium current in CA1 pyramidal neurons of young and adult rat hippocampus. AB - Serine protease thrombin, a key factor of blood coagulation, participates in many neuronal processes important for normal brain functioning and during pathological conditions involving abnormal neuronal synchronization, neurodegeneration and inflammation. Our previous study on CA3 pyramidal neurons showed that application ofthrombin through the activation of specific protease-activated receptor 1 (PAR1) produces a significant hyperpolarizing shift of the activation of the TTX sensitive persistent voltage-gated Na+ current (I(Nap)) thereby affecting membrane potential and seizure threshold at the network level. It was shown that PAR1 is also expressed in CA1 area of hippocampus and can be implicated in neuronal damage in this area after status epilepticus. The aim of the present study was to evaluate the effect of thrombin on I(NaP) in CA1 pyramidal neurons from adult and young rats. Using whole cell patch-clamp technique we demonstrate that thrombin application results in the hyperpolarization shift of I(NaP) activation as well as increase in the I(NaP) amplitude in both age groups. We have found that I(NaP) in pyramidal neurons of hippocampal CA 1 region is more vulnerable to the thrombin action than I(NaP) in pyramidal neurons of hippocampal CA3 region. We have also found that the immature hippocampus is more sensitive to thrombin action which emphasizes the contribution of thrombin-dependent pathway to the regulation of neuronal activity in immature brain. PMID- 26552300 TI - [PHYSICAL EXERCISE TRAINING CAN- CELS CONSTITUTIVE NOS UNCOUPLING AND INDUCED VIOLATIONS OF CARDIAC HEMODYNAMICS IN HYPERTENSION (PART III)]. AB - In the heart and heart mitochondria spontaneously hypertensive rats investigated the effect of physical exercise training (swimming in a moderate and excessive training mode) on the physiological indicators of cardiac hemodynamics and biochemical parameters that characterize the level of oxidative and nitrosative stress. The index of coupling Ca(2+)-dependent constitutive NO-synthases (cNOS = eNOS + nNOS) and biochemical index of dysfunction were calculated. It turned out that both modes of training is completely restored, and even exceed the reference values in untrained rats Wistar conjugate cNOS state and Ca(2+)-dependent synthesis of nitric oxide (NO). Intensity regime of exercise on the border of functionality have been ineffective for improving the functional state of the cardiovascular system and hypertension can provoke it further. Moderate physical training regime, on the contrary, improves the diastolic function of the heart due to an increase dP/dtmin, reducing end-diastolic pressure and a significant reduction in end-diastolic stiffness. Moderate exercise decreased peripheral resistance and cardiac afterload, as indicated by the decrease in end-systolic pressure and arterial stiffness, which contributed to more efficient and energy saving of heart work. Improve physiological indicators of cardiac hemodynamics and functional state of the heart in moderate mode of training correlated with changes in both the calculated indices. Moderate mode of training is recommended as a simple physiological preconditioning method for the prevention of cardiac dysfunction, hypertension as a result of state uncoupling cNOS and the resulting excessive generation of superoxide and, conversely, inhibition of Ca(2+) dependent synthesis of NO. PMID- 26552301 TI - [ROLE PHOSPHOINOSITID SIGNALING PATHWAY IN OPIOIDS CONTROL OF P2X3 RECEPTORS IN THE PRIMARY SENSORY NEURONS]. AB - Homomeric P2X3 receptors expressed in primary nociceptive neurons are crucial elements in the pain signal generation. In turn, opioid system regulates the intensity of this signal in both CNS and PNS. Here we describe the effects of opioids on P2X3 receptors in DRG neurons studied by using patch clamp technique. Activation of G-protein coupled opioid receptors by endogenous opioid Leu enkephalin (Leu), resulted in the two opposite effects on P2X3 receptor-mediated currents (P2X3 currents). In particular, application of 1 uM Leu lead to the complete inhibition of P2X3 currents. However, after pretreatment of the neurons with a Gi/o-protein inhibitor pertussis toxin (PT), the same concentration of Leu caused facilitation of P2X3 currents. PLC inhibitor U-73122 at concentration of 1 uM completely eliminated both facilitating and inhibitory effects of Leu on P2X3 currents. Thus, opioid receptor agonists cause two oppositely directed effects on P2X3 receptors in DRG neurons of rats and both of them are mediated through PLC signaling pathway. Our results point to a possible molecular basis of the mechanism for the well-known transition inhibitory action of opioids (analgesia) to facilitating (hyperalgesia). PMID- 26552302 TI - [ALLELIC VARIANT FREQUENCY OF PROMOTER (G(-47)-->A) gamma-CRYSTALLIN GENE AFFECTS THE LEVEL OF ITS EXPRESSION IN PLATELETS]. AB - To investigate the genetical precursors of cataract development the next groups were included: patients suffering from cataract (96) and 96 healthy persons. The determination of gamma-crystallin polymorphism (G(-47)-->A) (rs2289917) was provided using PCR method and further analyses of restriction fragment length polymorphism. These allelic variants have the significant different: G/G--35.37%, G/A--53.66%, A/A--10.98%, and G/G--55.06%, G/A--35.96%, A/A--8.99% comparing with the control group (P = 0.03, by chi2-test). While investigating the level of expression of gamma-crystallin gene (CRYGB) in platelets, showed that the quantity of mRNA in homozygotes G/G in 3.9 times (P < 0.05) higher than in carriers of A allele (genotype G/A and A/A). This paper shows the significant difference in distribution of CRYGB promoter (G(-47)-->A) genotypes in patients with cataract compared to the control group. Furthermore, here we provide the data concerning its functional meaning: level of mRNA expression of crystallin is different in carriers of various CRYGB promoter (G(-47)-->A) genotypes. PMID- 26552303 TI - [EFFECT OF PROPARGYLGLYCINE UPON CARDIOHEMODYNAMICS IN OLD RATS]. AB - Aging increases the risk of cardiovascular diseases. The objective of this study was to show the effect of propargylg- lycine (PPG) upon cardiohemodynamics in old rats. We used pressure-volume (PV) conductance catheter system (Millar Instruments, USA) in order to evaluate systolic and diastolic function in vivo. It has been shown that introducted PPG (11,31 mg/kg) decrises both arterial stiffness (by 1,5 times) and end-diastolic stiffness (by 2,1 times) in old rats. Using PPG in heart mitochondria resulted in increasing levels of H2S (by 112%), NO2- (by 162%) and in growing activity of cNOS (by 3 times). Additionally, PPG decreased the mitochondrial pools of the uric acid, the marker of the superoxide (*O2-) formation and of the ATP degradation. These results suggest that PPG activates alternative ways of H2S synthesis, stimulates the NO and H2S synthesis and suppresses the ATP degradation and *O2 formation. These actions of PPG improve arterial stiffness and end-diastolic stiffness. PMID- 26552304 TI - [CHANGES IN THE BRAIN TESTOSTERONE METABOLISM AND SEXUAL BEHAVIOR IN MALE RATS PRENATALLY EXPOSED TO METHYLDOPA AND STRESS]. AB - The changes of aromatase and 5alpha-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3 month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress. PMID- 26552305 TI - [EFFECT OF PEPTIDE SEMAX ON SYNAPTIC ACTIVITY AND SHORT-TERM PLASTICITY OF GLUTAMATERGIC SYNAPSES OF CO-CULTURED DORSAL ROOT GANGLION AND DORSAL HORN NEURONS]. AB - The influence of long-term culturing (12 days in vitro) of dorsal root ganglion (DRG) and dorsal horn (DH) neurons with peptide Semax on the level of synaptic activity at co-cultures, as well as short-term plasticity in sensory synapses were studied. It has been shown that neuronal culturing with peptide at concentrations of 10 and 100 uM led to increasing the frequency of spontaneous glutamatergic postsynaptic currents in DH neurons to 71.7 +/- 1.8% and 93.9 +/- 3.1% (n = 6; P < 0.001); Semax has a not significant effect on the amplitude and frequency of miniature glutamatergic currents, but causes an increase of the amplitudes of spontaneous postsynaptic currents, as well as elevates the quantum content. The data show the increase of multivesicular glutamate release efficiency in neural networks of co-cultures following incubation with the peptide. Also Semax (10 and 100 uM) induces changes of the basic parameters of short-term plasticity in sensory synapses: (1) increasing the paired-pulse ratio from 0.53 +/- 0.028 (n = 8) to 0.91 +/- 0.072 (n = 6, P < 0.01) and 0.95 +/- 0.026 (n = 7; P < 0.001); (2) reducing the ratio of the coefficients of variation (CV2/ CV1) from 1.49 +/- 0.11 (n = 8) to 1.02 +/- 0.09 (n = 6; P < 0.05) and 1.11 +/- 0.13 (n = 7; P < 0.0) respectively. The results indicate a stimulating effect of Semax on the activity of glutamatergic synapses in neural networks of co cultures, as well as the ability of the peptide to effectively modulate the short term plasticity in sensory synapses. PMID- 26552306 TI - [Impact of diabetic complications on neuromuscular transmission in the smooth muscle of the bladder of rats with experimental diabetes]. PMID- 26552307 TI - [THE INFLUENCE OF PROGENITOR NEURO- CELLS SUPERNATANT ON THE LYMPHO- CYTES CYTOTOXIC FUNCTION IN RATS WITH GLIOMA]. AB - The impact of rat neurogenic progenitor cells supernatant (RPNS) on the cytotoxic function of lymphocytes in rats under conditions of physiological norm and experimentally modeled tumor (brain glioma strain 101.8) was studied. The research was carried out in animals with inoculated tumor without RPNS injection and with different regimes of RPNS injection (thrice repeated from 5th to 10th day after glioma inoculation as well as 1 week and 1 month before tumor inoculation). Comparison groups included rats without glioma who triple injected with RPNS; and intact animals (control). RPNS was received from suspension of neurogenic progenitor cells (NPC) of rat brain on 14th day of gestation and injected intraperitoneally (0,12 mg per animal). Cytotoxic function of lymphocytes of experimental rats was evaluated in MTT-colorimetric test with allogeneic glioma cells. RPNS administration increased the cytotoxic activity of lymphocytes in vitro tests with allogeneic tumor cells in intact animals (to 37 38%) as well as in rats with glioma (to 11-22%). Under the RPNS influence the life expectancy and median survival of tumor-bearing animals increased (an average of 3-4 days). RPNS input modes such as triple injection from 5th to 10th day after glioma inoculation and 1 week before inoculation were the most effective. Thus, indirect tumor-inhibiting effect under intraperitoneal. RPNS administration in rats with glioma is demonstrated, which is obviously due to increased efficiency of cytotoxic function of immune cells of animals with inoculated tumor under the influence of the factors produced by NPC. PMID- 26552308 TI - [MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE]. AB - The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug PMID- 26552309 TI - [ACTIVATION OF PROTEIN C IN THE IN VITRO THROMBOLYSIS]. AB - Physiological conditions of formation and subsequent lysis of thrombus were reconstituted in vitro in our research. Thrombus formation was initiated either by addition of exogenous thrombin or by contact of blood with anionic surface, which stimulates spontaneous coagulation of blood. Tissue plasminogen activator and/or protein C were previously added in the blood sample. The time of the beginning and total degradation of formed thrombi as well as the level of PC in lysates was controlled then. Only an addition of protein C alone or in combination with tissue plasminogen activator led to the most effective lysis of thrombi: their residual weight was 18% and 5% comparing to control. Addition of exogenous tissue plasminogen activator alone or in combination with protein C caused a 83% and 74% decrease of PC level in lysates of spontaneously formed thrombi, and 72% and 56% decrease for thrombi formed by thrombin, respectively. Without an addition of tissue plasminogen activator protein C level in lysates of thrombi formed by thrombin was 54% down on spontaneously formed thrombi. Thus, changes of PC concentration in isolated volume of clot seem to be controlled by thrombin at the stage of thrombus formation and by fibrinolytic system at the stage of fibrinolysis. Concentration of PC in lysates from clots formed by exogenous thrombin was decreasing over the next 10 hours of thrombolysis, which can also be the evidence of the interaction between the fibrinolytic and PC activation systems. A hypothesis is. formulated about an existence of endothelium independent mechanism of PC activation in blood plasma with blood cells participation, which effectiveness increases in the process of thrombolysis. PMID- 26552310 TI - [INVESTIGATIONS OF SUBMICROSCOPIC ARCHITECTONICS SERTOLI AND LEYDIG CELLS AFTER HYDROCHLORIDE SEROTONIN DESTRUCTIVE IMPACT AND THE POSSIBILITY OF CORRECTION BY STIMULANTS OF METABOLIC PROCESSES]. AB - The results of study of ultrastructural changes in the Sertoli cells and Leydig's cells organelles after destructive influence of the serotonin hydrochloride and under influence bioglobin-U have been presented. It was shown that serotonin hydrochloride causes mitochondrial dysfunction and activates intracellular catabolic processes on the intracellular level. Bioglobin-U increases the activity and reparative synthetic reactions, reduced the degree of mitochondrial dysfunction and catabolic processes and activate the Leydig cell metabolism, and significantly reduces the number of foci destruction membranes of the endoplasmic reticulum, mitochondrial, and membranes of nucleus on the background of serotonin hydrochloride. PMID- 26552311 TI - [MODELING IN VITRO PATHWAYS OF ACTIVATION OF LIPID PEROXIDATION AND PROTEIN IN CHRONIC KIDNEY DISEASE]. AB - We studied the spontaneous and metal induced oxidation of lipids and proteins in in vitro modeling ways of lipid peroxidation and blood proteins in the formation of malondialdehyde (MDA) and protein carbonyl groups (PCG) in 86 patients with chronic pyelonephritis (cPN) and 64 patients chronic glomerulonephritis(cGN) without prejudice excretory function of the kidneys. Installed the increase in the blood of patients with cPN MDAs 2 times, MDAe--14%, PCG 1.5 times; and cGN- MDAs 2.3 times, MDAe--29%, PCG--2 times. Found increased MDA content and PCG in the blood of patients with cPN and more expressive when cGN. Stimulation of in vitro peroxidation processes contributed significantly increased of production of MDA comparedwith baseline. In the modeling in vitro ascorbate-dependent and NADPH dependent lipid peroxidation ways and the increase in protein production of MDA and PCG in both groups of patients, especially in the NADPH-dependent way, which must be considered in the correction of oxidative processes and antioxidant therapy appointment. PMID- 26552312 TI - [DYNAMICS OF SPECTRAL INDEXES OF HEART VARIABILITY RATE OF THE STUDENTS WITH DIFFERENT CHARACTER OF THE EDUCATIONAL LOADING]. AB - It has been analyzed in the article the change of spectral parameters of heart rate variability of the students of various disciplines influenced by conditions of educational and practical activities. It has been established that during training for women of all groups the studied parameters were reduced, and the students of "Physical culture" value LF increased almost in 2 times (P <= 0.05) in parallel with a decrease of VLF (of 902 [497; 1417] to 516 [401; 723] square milliseconds P <= 0.05). During the internship in students of "Foreign Languages" significantly increased rate of vegetative balance LF/HF (from 1,47 [0,88; 1,80] to 1,63 [1,18; 3,15] standard units, P <= 0.05) and all the studied parameters tended to increase (P >= 0.05). The growth of total power of spectrum (1969 [1298, 2398] to 3273 [1874; 4568] square milliseconds P50,05) in women specialty "Chemistry and Biology" testified to the increased activity of independent regulation circuit. In the students' "Physics and Mathematics" and "Physical Education" downward trend indicators had HF, VLF, TP and to increase--LF and LF HF (P >= 0.05). Changes of spectral indices point to strengthen sympathykotonic impacts and reduction of adaptive capacity in women "Physical Education" experiencing psycho-emotional tension combined with mental and physical load. PMID- 26552313 TI - [STATE OF AUTONOMIC NERVOUS SYSTEM OF MEDICAL HIGHER SCHOOL STUDENTS AND ITS RELATIONS WITH THEIR PHYSICAL ACTIVITY AND OPERATION WITH THE COMPUTER]. AB - The state of autonomic nervous system of the first-second years students and its relations with their physical activity, the experience and operation duration with computers have been explored. The observed base vegetative tonus was vagotonia and eytonia mainly (93.2%), vegetative reactivity was asympathetic and sympathetic (77.0%) mainly. Autonomic nervous system sympathetic part excitability in orthostatic test in 61.1% of the students was norm, while parasympathetic part reactivity in oculocardiac test was norm or reduced (72.8% of students) mainly. Work with the computer during 3 hours and more a day enhances sympathetic influences on heart activity, but increase of total work time promotes to relative decrease of sympatetic tonus. Vegetative reactivity grows both with increase of the operating time with the computer and with increase of the sport exercises. duration. PMID- 26552314 TI - [Changing Forensic Mental Health in France: A Review]. AB - This article describes the background and recent changes in French forensic mental health. The literature suggests that three law reforms have been crucial to changes in the mental health system. First, the Penal Code of 1992 redefined the provisions of criminal responsibility and introduced the category of diminished responsibility. Second, a controversial law for preventive detention (retention de surete) was enacted in 2008, according to which criminals with severe personality disorders are subject to incarceration even after the completion of their prison sentences if they are still considered to pose a danger to the public. Third, the revision of mental health laws in 2011 altered the forms of involuntary psychiatric treatments, stipulating a judge's authority to decide treatment. In parallel with these legal reforms, the psychiatric treatment system for offenders with mental disorders has been reconstructed. The number of difficult patient units (unites pour malades difficiles) has increased from four to ten across the nation in order to meet the needs of patients transferred from general psychiatric institutions for the reason of being unmanageable. In the penitentiary system, new facilities have been established to cope with the growing number of inmates with mental disorders. As background to these changes, it is pointed out that the current psychiatric system has undergone deinstitutionalization and become less tolerant of aggressive behavior in patients. In the broader context, public sensitivity towards severe crime, as shown by the sensation triggered by serious crimes conducted by pedophiles, seems to urge tough policies. In the 2000 s, several homicides committed by psychiatric patients had a great impact on the public, which led President Sarkozy to issue a statement calling for stronger security in psychiatric institutions. The harsh attitude of courts towards psychiatric practices is illustrated by a 2012 ruling; after a patient escaped from the hospital and hacked an elderly man to death, his psychiatrist was sentenced to a one-year suspended prison sentence for failing to recognize the danger that the patient posed to the public. Another lawsuit was raised against a psychiatrist following this case. Apparently, a sense of crisis is growing among psychiatric professionals. Their concerns are based on several points. Introduction of diminished responsibility may narrow the possibility of acquittal by reason of insanity, and lead to the criminalization of those with mental disorders. Dangerousness (dangerosite), pivotal in the procedure of preventive detention, is not a medical concept, but is instead based on the erroneous identification of criminality and mental disorders. Therefore, it is unreasonable to entrust the evaluation of dangerousness to psychiatric expertise. Court intervention in the process of deciding appropriate treatment may intensify judicialization (judiciarisation) of psychiatry. Establishment of facilities for prisoners within the mental health system would create a new segregating function of psychiatry. Thus, French experience seems to be figuring out all the challenges that contemporary metal health is facing. Above all, effective measures should be taken to prevent patients from entering the criminal justice system. Following this recommendation would be helpful in Japan, where a new forensic mental health system has just started. PMID- 26552315 TI - [Evidence-based Prospects for the Future of Mental Health Policies in Japan]. AB - The "Visions in Reform of Mental Health and Medical Welfare" is a report by the Headquarters for Mental Health and Welfare of the Ministry of Health, Labour and Welfare, with the Minister serving as the Director-General. The report generally presents the goals that must be realized over the next 10 years in order to reform the focus of Japan's mental health and medical welfare from "hospitalized medical treatment to living in the community". Reviewing the recent developments after the "Visions in Reform of Mental Health and Medical Welfare", evidence based prospects for the future of mental health policies in Japan are as follows: patient-centered, continuity of care, care management (CM), and vertical integration of multifunction of care are key functions of the new business model of mental health facilities under the regional medical vision. PMID- 26552316 TI - [Kinshicho Model for Community Care by Multifunctional Vertical Integration of Psychiatric Care]. AB - The future of psychiatric community care in Japan requires a medical team for outpatient care to offer support and take responsibility for a region; respecting human rights and supporting high risk patients who have concluded a long-period of hospitalized or repeated involuntary commitment, and for people who suffer from social withdraws over a long period of time. There are over 3,000 private psychiatric outpatient clinics in Japan. Over 400 of them are multifunctional psychiatric outpatient clinics that provide daycare services and outreach activities. In the future, if systematized those clinics entrusted by an administrative organ with performing as a "community mental health center". Multifunctional vertical integration of psychiatric care is possible in Japan to create a catchment area with 24 hours phone service and continued free access. PMID- 26552317 TI - [Approach of Private Hospitals to Support Individuality-respected Community Living]. AB - The government has taken a variety of measures to actualize the basic philosophy of the policy for"shifting medical treatment under hospitalization to regional medical treatment". The problems associated with mental disorders requiring long term psychiatric treatment and reducing psychiatric beds have been discussed from various viewpoints. Although the transfer of psychiatric medical treatment to regional medical treatment is taking place, it is true that some large barriers exist. According to research on the actual situation in 1954, 1,300,000 psychiatric disorders were estimated, including 350,000 disabilities requiring hospitalization, and mental beds available increased up to a maximum of 350,000 with government subsidies. In 1987, mental bed availability was controlled according to the local healthcare program. As a result, periods of psychiatric hospitalization became prolonged due to factors including social prejudice and the inadequacy of rehabilitation centers; it was called "social hospitalization". Nevertheless, it is true that private psychiatric hospitals have successfully provided various psychiatric medical services in order for people with disabilities to be able to live in the community. The Program for Dissolution of Social Hospitalization of Psychiatric Disabilities in 2000 started in Osaka. The Ministry of Health, Labour and Welfare started the Program for Hospital Discharge Promotion of Psychiatric Disabilities as a model program in 2003. This program was included in the Regional Life Support Program in Prefectural and City Governments, and expanded throughout Japan in 2006. The Regional Shift Support Special Action Program of Psychiatric Disabilities was started in 2008. The report of the "Symposium for Ideal Future Psychiatric Medical Welfare" as compiled in September 2009, and the target value was indicated there. Various measures were implemented in order to promote the basic philosophy for "shifting medical treatment under hospitalization to living in the community". In 2012, the Japan Psychiatric Hospitals Association, joined by the private psychiatric hospitals responsible for medical treatment under hospitalization, set forth their basic polity for "shifting medical treatment under hospitalization to regional medical treatment and medical care" as part of "Future Vision of Psychiatric Medical Treatment". PMID- 26552318 TI - [The Asahi Model-Regional Mental Health Services at Department of Psychiatry and Child Psychiatry, Asahi General Hospital]. AB - The Asahi model, Psychiatric Services of Department of Psychiatry and Child Psychiatry, Asahi General Hospital, is characterized by multiple dimensions of mental health services, such as multidisciplinary team approach, medical cooperation, specialized psychiatric treatment of acute care, clozapine and modified ECT, outreach services of home nursing and assertive community treatment, and the close and mutual coordination with housing services and social welfare services. The Asahi Model makes it possible to be deinstitutionalized, to improve patients satisfaction, to shorten hospitalization, to decrease psychiatric emergency visits and to be of service in a natural disaster. It also might prevent the relapse of schizophrenics within twelve months after discharge and improve the quality of mental health staffs trainings to support patients better. In the future, we will need to work on providing sectorized care, early psychosis intervention programs, to construct networking systems of clozapine and modified ECT, to strengthen growth of home nursing, and to take place mental health anti-stigma campaigns. PMID- 26552319 TI - [Practice of Community Psychiatry for the Treatment of Depression]. AB - The practice in the psychiatric division of Kitasato University East Hospital and Kitasato University Hospital has been emphasizing community psychiatry. The problems and proposed solutions are discussed. 1. Both hospitals are core hospitals located in Sagamihara City (Kanagawa Prefecture), which has no municipal hospital. 2. Kitasato University East Hospital has 94 beds in two closed wards and is one of the hospitals designated for psychiatric emergencies in Kanagawa Prefecture. 3. Over the last 10 years aroud Sagamihara City, cooperation between psychiatric hospitals and outpatient clinics, the treatment of patients with mental and physical diseases, improvement of the quality of psychiatric practice, emergency psychiatry, and imbalances in the incomes and workloads of psychiatrists have been problematic. 4. Problems that need to be solved in practice to treat depression involve inappropriate pharmacotherapy, disease mongering (the practice of widening the diagnostic boundaries of illnesses in order to expand the markets for drug treatment), clinical skills of psychiatrists, profitability, and medical institutions which cannot cope with regular patients in an emergency. 5. Up to now, we have established a consulting service ("Second opinion" clinic) at Sagamihara Mental Health and Welfare Center (Municipal institution), recommended patients' consultation with family pharmacists, and increased the frequency of conferences for doctors without the support of pharmaceutical companies. 6. In order to develop community psychiatric services for patients with depression, the author is preparing a community-based critical path for depression as well as community-based treatment network in the Sagamihara area. 7. The author believes that the urgent issue necessitates transparency and the increased visibility of psychiatric services. PMID- 26552320 TI - [What Psychiatrists Should Know about the Medical Documentation They Issue: Admission for Medical Care and Protection, Medical Treatment for Persons with Disabilities, Mental Health Disability Certification, etc]. AB - Psychiatrists issue a wide variety of documentation, among which are torms such as Registration of Admission for Medical Care and Protection, Periodic Report of Condition, Certification of Medical Treatment for Persons with Disabilities, and Mental Health Disability Certification, which are required under laws such as the Act on Mental Health and Welfare for the Mentally Disabled. These documents are important in that they are related to protecting the human rights of people with mental disorders, as well as securing appropriate medical and welfare services for them. However, in the course of reviewing and evaluating documentation at our Mental Health and Welfare Center, we encounter forms which are incomplete, or which contain inappropriate content. In order to protect the human rights of people with mental disorders, and to ensure the provision of appropriate medical and welfare services for them, I call on psychiatrists to issue carefully written and appropriate documentation. In this talk I will focus primarily on what psychiatrists should know when filling in forms in the course of their day-to-day clinical work. PMID- 26552321 TI - [Key Policy Challenges in Japanese Mental Health Relevant to the Next Generation of Japanese Psychiatrists: A Medical Officer's View]. AB - The Japanese mental health community is going through a series of major reforms initiated by the Ministry of Health, Labour and Welfare (MHLW) of Japan. As of 2013, mental disorder was included as the fifth priority national disease in the Regional Healthcare Strategic Plan. In the same year, the Act on Mental Health and Welfare of People with Mental Disorders was revised for the first time since 1999, and enacted on 1 April, 2014, aiming to promote community-based mental health, among others. With this as a background, this article aims to inform the next generation of psychiatrists regarding: 1) the process in which mental health reform takes place at the government level, 2) the role of medical officers instrumental in promoting such reform processes, and 3) an overview of the recent mental reform, with a focus on ministerial guidelines envisioning future directions. PMID- 26552322 TI - [Optimal Antipsychotic Dose and Dosing Interval in the Treatment of Schizophrenia]. AB - While antipsychotic treatment is essential for acute and maintenance phases of schizophrenia, antipsychotics can induce various undesirable side effects. Thus, antipsychotic dose and dosing interval should be optimized for each patient. Some of the side effects of antipsychotics, including cognitive impairment, are related to antipsychotic dose. To date, there have been only a few studies examining the effect of atypical antipsychotic dose reduction on clinical outcomes, and there has been no study employing neurocognitive assessments. Based on this background, we conducted a randomized controlled trial and found that atypical antipsychotic reduction significantly improved cognitive function without an increased risk of relapse. In addition, we analyzed the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) data, revealing that there were no significant differences in clinical outcomes between once- vs. twice-daily perphenazine dosing regimens; however, the mean dose of perphenazine was significantly lower with once-daily dosing than that with twice-daily dosing. These findings suggest the possibility of effective antipsychotic treatment with lower doses and longer dosing intervals. PMID- 26552323 TI - Predictors of Mortality in Patients with COPD and Chronic Respiratory Failure: The Quality-of-Life Evaluation and Survival Study (QuESS): A Three-Year Study. AB - Previous studies sought to identify survival or outcome predictors in patients with COPD and chronic respiratory failure, but their findings are inconsistent. We identified mortality-associated factors in a prospective study in 21 centers in 7 countries. Follow-up data were available in 221 patients on home mechanical ventilation and/or long-term oxygen therapy. MEASUREMENTS: diagnosis, co morbidities, medication, oxygen therapy, mechanical ventilation, pulmonary function, arterial blood gases, exercise performance were recorded. Health status was assessed using the COPD-specific SGRQ and the respiratory-failure-specific MRF26 questionnaires. Date and cause of death were recorded in those who died. Overall mortality was 19.5%. The commonest causes of death were related to the underlying respiratory diseases. At baseline, patients who subsequently died were older than survivors (p = 0.03), had a lower forced vital capacity (p = 0.03), a higher use of oxygen at rest (p = 0.003) and a worse health status (SGRQ and MRF26, both p = 0.02). Longitudinal analyses over a follow-up period of 3 years showed higher median survival times in patients with use of oxygen at rest less than 1.75 l/min and with a better health status. In contrast, an increase from baseline levels of 1 liter in O2 flow at rest, 1 unit in SGRQ or MRF26, or 1 year increase in age resulted in an increase of mortality of 68%, 2.4%, 1.3%, and 6%, respectively. In conclusion, the need for oxygen at rest, and health status assessment seems to be the strongest predictors of mortality in COPD patients with chronic respiratory failure. PMID- 26552325 TI - Preparation of Honeycomb SnO2 Foams and Configuration-Dependent Microwave Absorption Features. AB - Ordered honeycomb-like SnO2 foams were successfully synthesized by means of a template method. The honeycomb SnO2 foams were analyzed by X-ray diffraction (XRD), thermogravimetric and differential scanning calorimetry (TG-DSC), laser Raman spectra, scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR). It can be found that the SnO2 foam configurations were determined by the size of polystyrene templates. The electromagnetic properties of ordered SnO2 foams were also investigated by a network analyzer. The results reveal that the microwave absorption properties of SnO2 foams were dependent on their configuration. The microwave absorption capabilities of SnO2 foams were increased by increasing the size of pores in the foam configuration. Furthermore, the electromagnetic wave absorption was also correlated with the pore contents in SnO2 foams. The large and high amounts pores can bring about more interfacial polarization and corresponding relaxation. Thus, the perfect ordered honeycomb like SnO2 foams obtained in the existence of large amounts of 322 nm polystyrene spheres showed the outstanding electromagnetic wave absorption properties. The minimal reflection loss (RL) is -37.6 dB at 17.1 GHz, and RL less than -10 dB reaches 5.6 GHz (12.4-18.0 GHz) with thin thickness of 2.0 mm. The bandwidth (< 10 dB, 90% microwave dissipation) can be monitored in the frequency regime of 4.0 18.0 GHz with absorber thickness of 2.0-5.0 mm. The results indicate that these ordered honeycomb SnO2 foams show the superiorities of wide-band, high-efficiency absorption, multiple reflection and scatting, high antioxidation, lightweight, and thin thickness. PMID- 26552324 TI - Comparison of virulence between Paracoccidioides brasiliensis and Paracoccidioides lutzii using Galleria mellonella as a host model. AB - Paracoccidioidomycosis is a systemic mycosis, endemic in Latin America. The etiologic agents of this mycosis are composed of 2 species: Paracoccidioides brasiliensis and P. lutzii. Murine animal models are the gold standard for in vivo studies; however, ethical, economical and logistical considerations limit their use. Galleria mellonella is a suitable model for in vivo studies of fungal infections. In this study, we compared the virulence of P. brasiliensis and P. lutzii in G. mellonella model. The deaths of larvae infected with P. brasiliensis or P. lutzii were similar, and both species were able to reduce the number of hemocytes, which were estimated by microscopy and flow cytometer. Additionally, the phagocytosis percentage was similar for both species, but when we analyze hemocyte-Paracoccidioides spp. interaction using flow cytometer, P. lutzii showed higher interactions with hemocytes. The gene expression of gp43 as well as this protein was higher for P. lutzii, and this expression may contribute to a greater adherence to hemocytes. These results helped us evaluate the behavior of Paracoccidioides spp in G. mellonella, which is a convenient model for investigating the host-Paracoccidioides spp. interaction. PMID- 26552326 TI - Cesarean hysterectomy for placenta previa accreta in dichorionic twin: a surgery that remains challenging. PMID- 26552327 TI - Biological diagnosis of diabetes mellitus. AB - Diabetes mellitus is a common disease whose complications are severe. For decades, the diagnosis of diabetes and prediabetes was using only fasting glucose or glucose two hours during an oral glucose tolerance test. Recently, it is possible to use HbA1c. Each of these tests has advantages and limitations that must be well known by clinicians for better care for patients. So they could use one, two or three of this tests to reach to a proper diagnosis. The aim of this article is about the strong and weak points of these tests. PMID- 26552328 TI - Screening of metal uptake by plant colonizers growing on abandoned copper mine in Kapunda, South Australia. AB - Systematic site survey for sample collection and analysis was conducted at a derelict copper (Cu) mine at Kapunda, South Australia. Cu concentrations in the soils at this former mine ranged from 65-10107 mg kg(-1). The pH and EC varied widely in the 3.9-8.4 and 152-7311 uS ranges, respectively. Nine plant species growing over the copper mine site were selected to screen for metal uptake to determine their suitability for phytoremediation. The Australian native tree species Eucalyptus camaldulensis indicated enrichment factor (EF) of 2.17, 1.89, and 1.30 for Cu, Zn, and Pb, respectively, suggesting that this species of tree can accumulate these metals to some degree. The stress-resistant exotic olive, Olea europaea exhibited EF of <= 0.01 for Cu, Cd, and Pb, and 0.29 for Zn, which is characteristic of an excluder plant. Acacia pycnantha, the Australian pioneer legume species with EF 0.03, 0.80, 0.32, and 0.01 for Cu, Zn, Cd, and Pb, respectively, emerged as another strong metal excluder and consequently as an ideal metal stabilizer. PMID- 26552329 TI - The pathogenic activity of anti-desmoglein autoantibodies parallels disease severity in rituximab-treated patients with pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease mediated by IgG autoantibodies targeting desmogleins (Dsgs). The anti-CD20 monoclonal antibody rituximab is increasingly used in corticosteroid-resistant PV patients. In a subset of rituximab-treated patients in remission, high ELISA index values have been reported; however, their significance remains so far unclear. OBJECTIVE: To address the discrepancy between anti-Dsg3 serum antibody titers and disease severity. MATERIALS & METHODS: 6 rituximab-treated PV patients were prospectively followed-up for two years and anti-Dsg3 autoantibodies levels and pathogenic activity were measured. RESULTS: All patients achieved complete remission without any serious side effects. Both anti-Dsg3 autoantibodies (p = 0.031) and their pathogenic activity (p = 0.003) were significantly related to disease severity. However, in selected patients, the dissociation index was a more sensitive indicator for PV clinical activity than the ELISA index. CONCLUSION: Our findings have demonstrated the existence of non-pathogenic autoantibodies in PV patients in remission, establishing the basis for the design of a system able to precisely monitor the course of disease. PMID- 26552331 TI - New bigenic mouse model increases the understanding of genetic synergism in the progression of prostate cancer. AB - A new bigenic mouse model, engineered with the overexpression of PSGR and the knockout of PTEN, has been used to study the relationship between 2 genes and disease progression. A study in Oncogene (Rodriguez et al.) has shown that these 2 genetic polymorphisms synergistically promote the development of prostate cancer. PMID- 26552330 TI - Disparities in cervical cancer survival among Asian-American women. AB - PURPOSE: We compared overall survival and influencing factors between Asian American women as a whole and by subgroup with white women with cervical cancer. METHODS: Cervical cancer data were from the Surveillance, Epidemiology, and End Results registry; socioeconomic information was from the Area Health Resource File. We used standard tests to compare characteristics between groups; the Kaplan-Meier method with log-rank test to assess overall survival and compare it between groups; and Cox proportional hazards models to determine the effect of race and other covariates on overall survival (with and/or without age stratification). RESULTS: Being 3.3 years older than white women at diagnosis (P < .001), Asian-American women were more likely to be in a spousal relationship, had more progressive disease, and were better off socioeconomically. Women of Filipino, Japanese, and Korean origin had similar clinical characteristics compared to white women. Asian-American women had higher 36- and 60-month survival rates (P = .004 and P = .013, respectively), higher overall survival rates (P = .049), and longer overall survival durations after adjusting for age and other covariates (hazard ratio = 0.77, 95% confidence interval: 0.68-0.86). Overall survival differed across age strata between the two racial groups. With the exception of women of Japanese or Korean origin, Asian-American women grouped by geographic origin had better overall survival than white women. CONCLUSIONS: Although Asian-American women, except those of Japanese or Korean origin, had better overall survival than white women, their older age at cervical cancer diagnosis suggests that they have less access to screening programs. PMID- 26552332 TI - Intermittent sharp facial pain starting at the mandibular right first molar: A diagnostic challenge. PMID- 26552333 TI - Soft-tissue calcification on a panoramic radiograph: A diagnostic perplexity. PMID- 26552334 TI - Prevalence of clinical signs of intra-articular temporomandibular disorders in children and adolescents: A systematic review and meta-analysis. AB - BACKGROUND: The aim of this systematic review and meta-analysis was to assess the prevalence of clinical signs of temporomandibular joint (TMJ) disorders in children and adolescents. TYPE OF STUDIES REVIEWED: The authors selected only studies in which the investigators' primary objective was to evaluate the prevalence of signs of TMJ disorders according to the international Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) in children and adolescents. The authors performed electronic searches without language restriction in 5 databases. The authors also assessed quality. RESULTS: In this review and meta-analysis, the authors included 11 articles that described studies in which 17,051 participants had been enrolled. The overall prevalence of clinical signs of intra-articular joint disorders was 16% (95% confidence interval [CI], 11.59-19.94; n = 17,051). The prevalence of TMJ sounds (click and crepitation) was 14% (95% CI, 9.67-19.79; n = 11,316). The most prevalent sign was clicking (10.0%; 95% CI, 7.97-12.28; n = 9,665) followed by jaw locking (2.3%; 95% CI, 0.56-5.22; n = 5,735). CONCLUSIONS AND PRACTICAL IMPLICATIONS: One in 6 children and adolescents have clinical signs of TMJ disorders. The results of this systematic research study can alert dentists about the importance of looking for signs of TMD in children and adolescents. PMID- 26552335 TI - Drugs related to the etiology of molar incisor hypomineralization: A systematic review. AB - BACKGROUND: Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. TYPES OF STUDIES REVIEWED: The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. RESULTS: Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. CONCLUSIONS: More well-designed prospective studies are needed to clarify the relationship between MIH and medication. PRACTICAL IMPLICATIONS: It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease. PMID- 26552336 TI - Characteristics of product recalls of biopharmaceuticals and small-molecule drugs in the USA. AB - Compared with chemically synthesized small-molecule drugs, the manufacturing process of biopharmaceuticals is more complex. Unexpected changes to product characteristics following manufacturing changes have given rise to calls for robust systems to monitor the postauthorization safety of biopharmaceuticals. We compared quality-related product recalls in the USA of biopharmaceuticals and of small molecules. Although the reasons for recalls for biopharmaceuticals differed from those for small molecules, adverse events were rarely reported. The relative contribution of recalls that could cause serious adverse health consequences was not greater for biopharmaceuticals than for small molecules. Therefore, these data do not give rise to concerns that biopharmaceuticals are more frequently associated with unexpected safety concerns. PMID- 26552337 TI - IFN-lambda therapy: current status and future perspectives. AB - Interferon-lambda (IFN-lambda), the most recently described type III IFN, plays a crucial part by acting on specific cell types, controlling viral infections and establishing robust innate immunity against cancer. In contrast to IFN-alpha or IFN-gamma, IFN-lambda has a restricted cell response pattern, which could make this new IFN a better choice for disease targeting and reducing adverse events. Although IFN-lambda is considered to have pivotal roles in cancer, viral infections and autoimmune diseases, clinical trials have only been conducted for treatment of chronic hepatitis C virus infection. In this review, we discuss the current and the potential clinical applications of IFN-lambda in the context of current IFN therapy. PMID- 26552338 TI - [Unusual presentation of anetodermic Pilomatricoma after insect bite]. PMID- 26552339 TI - The evaluation of an oral health education program for midwives in Australia. AB - BACKGROUND: Antenatal care providers are now recommended to promote oral health during pregnancy and provide dental referrals. However, midwives in Australia are not trained to undertake this role. To address this shortcoming, an online evidence based midwifery initiated oral health (MIOH) education program was systematically developed as a professional development activity. AIM: This study aimed to evaluate the effectiveness of the program in improving the oral health knowledge of midwives and assess their confidence to promote maternal oral health post training. METHODS: The program was evaluated using a pre-post test design involving 50 midwives purposively recruited from two states in Australia. The pre post questionnaire contained 24 knowledge items previously pilot tested as well as items exploring confidence in promoting oral health and perceptions of the program. FINDINGS: The results showed a significant improvement in the oral health knowledge (?21.5%, p<0.001) of midwives after completion of the program. The greatest improvement in knowledge occurred in key areas vital in promoting maternal oral health namely the high prevalence of dental problems and its impact on birth and infant outcomes. The majority also reported being confident in introducing oral health into antenatal care (82%) and referring women to dental services (77.6%) after undertaking the education program. CONCLUSION: The MIOH education program is a useful resource to equip midwives with the necessary knowledge and skills to promote oral health during pregnancy. The program is accessible and acceptable to midwives and can potentially be transferable to other antenatal care providers. PMID- 26552340 TI - 3D vertical nanostructures for enhanced infrared plasmonics. AB - The exploitation of surface plasmon polaritons has been mostly limited to the visible and near infrared range, due to the low frequency limit for coherent plasmon excitation and the reduction of confinement on the metal surface for lower energies. In this work we show that 3D--out of plane--nanostructures can considerably increase the intrinsic quality of the optical output, light confinement and electric field enhancement factors, also in the near and mid infrared. We suggest that the physical principle relies on the combination of far field and near field interactions between neighboring antennas, promoted by the 3D out-of-plane geometry. We first analyze the changes in the optical behavior, which occur when passing from a single on-plane nanostructure to a 3D out-of plane configuration. Then we show that by arranging the nanostructures in periodic arrays, 3D architectures can provide, in the mid-IR, a much stronger plasmonic response, compared to that achievable with the use of 2D configurations, leading to higher energy harvesting properties and improved Q factors, with bright perspective up to the terahertz range. PMID- 26552341 TI - Breast pump use amongst mothers of healthy term infants in Melbourne, Australia: A prospective cohort study. AB - OBJECTIVE: this paper describes the use of breast pumps amongst a group of mothers of healthy term infants in Melbourne, Australia, between birth and six months post partum. DESIGN: a prospective cohort study; data were collected using structured questionnaires. PARTICIPANTS: 1003 postpartum women who had given birth to healthy infants at term were recruited from three Melbourne maternity hospitals between July 2009 and April 2011. Data were collected by face-to-face interview at recruitment and by telephone interview three and six months later. FINDINGS: at recruitment (24 to 48 hours post partum), 60% (605/1003) of women already had a breast pump. At two weeks post partum expressing was common; 62% (290/466) of women had expressed by this time, with 40% (186/466) doing so several times a day. By six months post partum 83% (754/911) of the women had a breast pump and 40% (288/715) were expressing, although most just occasionally. The most common reasons for any expressing in the first six months were 'to be able to go out and leave the baby' (35%; 268/772); milk supply 'not enough'(27%; 207/772); and having 'too much' milk (19%; 147/772). The increasing popularity of expressing breast milk to feed infants is not driven by women returning to the workforce, as only 10% of women (80/772) expressed because they had returned to paid employment. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: health professionals should be aware that in some settings breast pump use is common in the first six months, and this is not always related to maternal workforce participation. PMID- 26552342 TI - Sexuality and mental health: Issues and what next? AB - Human sexuality plays a major role in an individual's existence and functioning. In addition, rightly or wrongly sexuality often defines people and also affects social attitudes. These attitudes, if negative, can contribute to stigma and prevent people from help seeking if they are suffering from mental health problems. Recent changes in policy towards same-sex relationships have been positive in many countries including the UK and the USA, whereas in others such as Russia and Uganda attitudes have become more negative and punitive. Sexual activity is seen as having both pleasurable and procreational functions which contribute to society's attitudes to homosexual behaviour. Inevitably, individual responses to their own sexuality and sexual behaviour will be influenced by social attitudes. To ensure that those with various sexual variations can access psychiatric services without discrimination, various levels of interventions are needed. Here we discuss different levels of intervention and organizational change that may make it possible. Social organization and institutional organization of services need to be sensitive, especially as rates of many mental disorders are high in individuals who may be sexually variant. Those providing services need to understand their own negative attitudes as well as prejudices to ensure that services are emotionally accessible. PMID- 26552343 TI - Electrostatic Field Invisibility Cloak. AB - The invisibility cloak has been drawing much attention due to its new concept for manipulating many physical fields, from oscillating wave fields (electromagnetic, acoustic and elastic) to static magnetic fields, dc electric fields, and diffusive fields. Here, an electrostatic field invisibility cloak has been theoretically investigated and experimentally demonstrated to perfectly hide two dimensional objects without disturbing their external electrostatic fields. The desired cloaking effect has been achieved via both cancelling technology and transformation optics (TO). This study demonstrates a novel way for manipulating electrostatic fields, which shows promise for a wide range of potential applications. PMID- 26552344 TI - Acetohydroxyacid synthase FgIlv2 and FgIlv6 are involved in BCAA biosynthesis, mycelial and conidial morphogenesis, and full virulence in Fusarium graminearum. AB - In this study, we characterized FgIlv2 and FgIlv6, the catalytic and regulatory subunits of acetohydroxyacid synthase (AHAS) from the important wheat head scab fungus Fusarium graminearum. AHAS catalyzes the first common step in the parallel pathways toward branched-chain amino acids (BCAAs: isoleucine, leucine, valine) and is the inhibitory target of several commercialized herbicides. Both FgILV2 and FgILV6 deletion mutants were BCAA-auxotrophic and showed reduced aerial hyphal growth and red pigmentation when cultured on PDA plates. Conidial formation was completely blocked in the FgILV2 deletion mutant DeltaFgIlv2-4 and significantly reduced in the FgILV6 deletion mutant DeltaFgIlv6-12. The auxotrophs of DeltaFgIlv2-4 and DeltaFgIlv6-12 could be restored by exogenous addition of BCAAs but relied on the designated nitrogen source the medium contained. Deletion of FgILV2 or FgILV6 also leads to hypersensitivity to various cellular stresses and reduced deoxynivalenol production. DeltaFgIlv2-4 lost virulence completely on flowering wheat heads, whereas DeltaFgIlv6-12 could cause scab symptoms in the inoculated spikelet but lost its aggressiveness. Taken together, our study implies the potential value of antifungals targeting both FgIlv2 and FgIlv6 in F. graminearum. PMID- 26552345 TI - Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. AB - The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non-responder microbiota. Our findings indicate that Prevotella plays a role in the BKB-induced improvement in glucose metabolism observed in certain individuals, potentially by promoting increased glycogen storage. PMID- 26552346 TI - Antioxidant and antithrombotic therapies for diabetic kidney disease. AB - With an increasing incidence, diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease and end-stage renal disease, and conventional therapies did not change this situation. This study intended to review and analyze the antioxidant and antithrombotic treatments of DKD for seeking novel therapeutic strategies. Relevant articles involved with antioxidant and antithrombotic treatments in DKD were retrieved and analyzed via systematic assessment. Meta-analysis showed that pancreatic kallikrein definitely reduced glycated hemoglobin in DKD patients (mean difference, 0.36%; 95% confidence interval, 0.08% to 0.63%; P = .01). Apart from the classic agents such as aspirin, novel drugs such as pancreatic kallikrein, sulodexide, and especially the traditional Chinese medicine including Tripterygium wilfordii and lumbrukinase, exert beneficial effects in DKD patients. Antioxidant and antithrombotic treatments are beneficial for DKD patients and represent promising therapeutic strategies in the future. PMID- 26552347 TI - Ameliorative effect of green tea against contrast-induced renal tubular cell injury. AB - INTRODUCTION: Reactive oxygen species are a mediator of kidney damage by contrast media, and green tea is a potent-free radical scavenger. This study was designed to examine whether green tea could protect against the nephrotoxicity induced by contrast media. MATERIALS AND METHODS: Forty rats were randomly divided into 4 groups. Group 1 was control; group 2 received contrast medium (intravenous iodixanol, 10 mL/kg, as a single dose); group 3 received contrast medium and then green tea extract for 3 days (10 mg/kg/d, intraperitoneal); and group 4 first received green tea and then contrast medium. Histological changes (degeneration, vacuolization of tubular renal cells, dilatation of tubular lumen, and presence of debris in the lumens) were assessed and recorded as scores from zero to 4. The sum of scores were used as the overal renal injury level. RESULTS: Groups 3 and 4 with green tea treatment had significantly higher overall scores than the control group, but significantly lower scores than group 2 with contrast medium only. A similar trend was seen for dilatation and degeneration levels. Vacuolization level was not significantly lower in the green tea groups as compared to the contrast medium group. Debris level was not significantly lower in group 3 than group 2. The differences were not significant between groups 3 and 4. Conclusions. We observed beneficial effect of green tea against nephrotoxicity of contrast media. Green tea extract may offer an inexpensive and nontoxic intervention strategy in patients with a risk for nephrotoxicity with contrast media. PMID- 26552348 TI - Impact of creatinine clearance on Helicobacter pylori eradication rate in patients with peptic ulcer disease. AB - INTRODUCTION: Gastrointestinal complaints are common in patients with kidney failure. The aim of this study was to investigate the effect of creatinine clearance on Helicobacter pylori (HP) eradication rate in patients with peptic ulcer disease. MATERIALS AND METHODS: In this clinical trial, 132 patients with a range of kidney function (normal to end-stage renal disease) and peptic ulcer disease with HP infection were enrolled and divided into 5 groups by their creatinine clearance. For all patients, a 14-day standard regimen of triple therapy for peptic ulcer was started with omeprazole, 20 mg; clarithromycin, 500 mg; and amoxicillin, 1 g; twice per day. After 6 weeks, HP eradication rate were evaluated and compared between the groups with urea breath test. RESULTS: The mean age of the participants was 44.84 +/- 12.20 years and 68 (51.5%) were women. The five groups were not significantly different in terms of age, sex distribution, or body mass index. The results of urea breath test at 6 weeks were positive in 23 patients (17.4%). There was no significant difference in HP eradication rate (negative urea breath test) between the five groups. CONCLUSIONS: This study showed no association between the success rate of eradication of HP infection and kidney function. PMID- 26552349 TI - Improvement of immune dysfunction in dogs with multiple organ dysfunction by high volume hemofiltration. AB - INTRODUCTION: Observing the effects of high-volume hemofiltration (HVHF) treatment on the monocytes apoptosis, antigen presentation, and secretion function, this study investigated the mechanism of HVHF effect on immunity homeostasis in multiple organ dysfunction syndrome (MODS) in an animal model. MATERIALS AND METHODS: Lipopolysaccharides were administered in 12 Beagle dogs in order to induce MODS. Six dogs were randomly assigned to receive HVHF treatment for 12 hours (HVHF group) and the rest did not receive any treatment (the MODS group). The expression of DLA-DR, apoptosis, and cytokine levels were measured at 7 time points: normal condition (T1), after operation (T2), and zero, 3, 6, 9, and 12 hours after endotoxin injection (T3 to T7, respectively). RESULTS: Apoptosis of CD14+ mononuclear cell increased in early and late stages gradually in the MODS group and began to decline gradually after the HVHF treatment. There was a significant difference between the two groups at time points T2 to T7 (P < .01). After HVHF, the impaired expression of dog leukocyte antigen-DR showed an improvement trend in the HVHF group, which was significant better at T5 and T7 than that in the MODS group (P < .05). Interleukin-4 secretion increased significantly with HVHF and was significantly higher at time points T4 to T7 as compared with the MODS group (P < .01). Conclusions. High-volume hemofiltration can alleviate the mononuclear cell apoptosis, improve antigen-presenting function and secretion function, inhibit the release of inflammatory factors, and maintain immune homeostasis, and consequently alleviate symptoms of MODS effectively. PMID- 26552350 TI - Regulation of cyclic adenosine monophosphate response element binding protein on renin expression in kidney via complex cyclic adenosine monophosphate response element-binding-protein-binding protein/P300 recruitment. AB - INTRODUCTION: Renin synthesis and release is the rate-limiting step in the renin angiotensin system, because cyclic adenosine monophosphate (cAMP) has been identified as dominant pathway for renin gene expression, and cAMP response element-binding protein (CREB) is found in the human and mouse renin promoter. This study aimed to evaluate the role of CREB in expression of the renin gene. MATERIALS AND METHODS: We created conditional deletion of CREB in mice with low sodium diet, specifically in renin cells of the kidney. To assess the effect of CREB on renin expression, immunostaining of renin was used in samples from wild type mice and mice with gene knock-down of CREB. Cyclic AMP response element binding-protein-binding protein (CBP) and p300 were measured in cultured renin cells of the mice, and RNA detection was done with real-time polymerase chain reaction. RESULTS: With low-sodium diet, renin was expressed along the whole wall of the afferent glomerular arterioles in wild-type mice, while there was no increase or even decrease in renin expression in CREB-specific deletion mice; RNA level of renin in cultured cells decreased by 50% with single knock-down of CREB, CBP, or p300, and decreased 70% with triple knock-down of CREB, CBP, and p300. CONCLUSIONS: This study found that CREB was important for renin synthesis and the role of CREB can be achieved through the recruitment of co-activators CBP and p300. PMID- 26552351 TI - Prevalence of chronic kidney disease and its risk factors in Gonabad, Iran. AB - INTRODUCTION: Chronic kidney disease (CKD) is an important health problem in Iran, with an increasing prevalence rate. Knowledge about the prevalence and risk factors of this disease in different health jurisdictions can help in planning to control this condition. MATERIALS AND METHODS: In this cross-sectional study, 1285 individuals aged between 20 and 60 years old were recruited. Participants were selected from the general population residing in Gonabad, Iran, via simple random sampling in 2012. Demographic data were collected. Urine and blood test were performed, and the glomerular filtration rate was estimated based on the simplified Modification of Diet in Renal Disease equation. RESULTS: Sixty-five participants (5.1%) had CKD (5.1% men and 5% women; P = .90). The mean age was significantly higher in the CKD group (P = .001). Hypertension and diabetes mellitus were significantly more prevalent among the participants with CKD than those without CKD (P < .001 for both). Proteinuria was significantly associated with CKD, whereas a history of urinary tract infection, a history of nephrolithiasis, smoking, serum uric acid level, lipid profile, and blood glucose level were not. CONCLUSIONS: Chronic kidney disease has a high prevalence rate in this part of Iran. We suggest further studies in other parts of our country for the better estimation of the prevalence of CKD in Iran and for better planning to prevent and treat this condition. PMID- 26552352 TI - Effect of N-acetylcysteine on inflammation biomarkers in pediatric acute pyelonephritis: a randomized controlled trial. AB - INTRODUCTION: This study was designed to investigate the effect of N acetylcysteine (NAC), as a potent and safe antioxidant, on inflammatory biomarkers of acute pyelonephritis in pediatric patients. MATERIALS AND METHODS: Children (< 15 years old) admitted with a diagnosis of pyelonephritis were recruited in a randomized placebo-controlled trial. They were randomly allocated to 2 groups and recieved placebo or NAC effervescent tablets with daily dose based on their weight, for 5 days. The children were evaluated for serum procalcitonin level, leukocyte count, C-reactive protein (CRP), serum creatinine, and clinical symptoms on the 1st and the 5th days. RESULTS: Seventy patients, 35 in each group, with a mean age of 5.54 +/- 3.10 years completed the study. There was no significant difference between the two groups in the amount of changes in procalcitonin levels after 5 days (P = .90). Within-group analysis confirmed CRP reduction in both groups (P < .001); however, between-group analysis did not show significant difference in CRP reductions, either (P = .65). No significant differences were found between the two groups in the day of resolving pyuria (P = .46), day of resolving bacteriuria (P = .81), or reductions in leukocyte count (P = .64) and neutrophil count (P = .49). CONCLUSIONS: A short period of NAC administration with the recommended doses could not lead to a significant decrease in inflammation biomarkers. Studies on higher doses and longer duration of NAC administration along with evaluation of the long-term effects of the intervention by tools such as renal scntigraphy are suggested. PMID- 26552353 TI - Relationship between ankle-brachial index and left ventricle ejection fraction in patients on hemodialysis. AB - INTRODUCTION: Ankle-brachial index (ABI) is a noninvasive test which employs as a diagnostic marker of atherosclerotic peripheral vascular disease in hemodialysis patients. This study aimed to investigate the association between ABI and left ventricular ejection fraction (LVEF) in patients on hemodialysis. MATERIALS AND METHODS: Eighty-six patients with end-stage renal disease undergoing hemodialysis and 100 patients referred for echocardiography without apparent kidney disease were included. Ankle-brachial index was calculated by dividing the highest ankle pressure (the left and right dorsalis pedis and posterior tibial) by the brachial systolic blood pressure on the arm with no arteriovenous fistula. The relationship between ABI and LVEF was investigated. RESULTS: The hemodialysis patients were older on average than the control group (P = .004). The total average of ABI in the hemodialysis group was less than 0.9 in 20 patients (23.3%) and 0.9 to 1.3 in 66 (76.7%). These were 11 (11%) and 89 (89%), respectively, among the controls (P = .02). The mean LVEF was 49.7 +/- 8.6% in the hemodialysis patients and 53.8 +/- 9.5% in the controls (P = .003). There was a significant correlation between LVEF and ABI in the hemodialysis patients (r = 0.06; P = .001), and ABI could predict the LVEF with sensitivity and specificity of 90% and 94.1%, respectively (positive predictive value, 34.6%; negative predictive value, 48.5%). CONCLUSIONS: These findings show that ABI may be applied in predicting the presence of left ventricular systolic dysfunction in hemodialysis patients. Further studies are recommended to confirm this association. PMID- 26552354 TI - Lithogenic activity as a factor to consider in the metabolic evaluation of patients with calcium lithiasis. AB - Metabolic evaluation is important in high-risk patients with a history of urinary calculi, in order to prevent recurrence. This study aimed to compare patients with calcium calculi and mild lithogenic activity with those with moderate to severe lithogenic activity. Patients with moderate to severe activity had higher levels of urinary calcium level (271.9 mg/24h versus 172.1 mg/24 h, P < .001), uric acid (612.3 mg/24 h versus 528.9 mg/24h, P = .008), and fasting calcium creatinine ratio (0.16 versus 0.12, P = .001) compared to those with mild lithogenic activity. No association was observed between lithogenic factors in 24 hour urine and mild lithogenic activity in multivariable analysis. We initially thought that in patients who develop recurrent calculi after 5 years or who have mild lithogenic activity, complete metabolic evaluation would not be necessary. However, based on our study findings, it may be important to conduct further studies assessing the lithogenic activity. PMID- 26552355 TI - Coexistence of immunoglobulin M nephropathy and autoimmune hemolytic anemia: 2 rare entities. AB - Immunoglobulin M (IgM) nephropathy is described as mesengial proliferative glomerulonephritis with diffuse mesengial IgM deposition. We report a patient diagnosed with IgM nephropathy and concomitant autoimmune hemolytic anemia syndrome associated with cold-reacting autoantibodies. Complete remission was achieved with systemic corticosteroid and plasmapheresesis. PMID- 26552356 TI - A mineralogical study in contrasts: highly mineralized whale rostrum and human enamel. AB - The outermost enamel of the human tooth and the rostrum of the whale Mesoplodon densirostris are two highly mineralized tissues that contain over 95 wt.% mineral, i.e., bioapatite. However, the same mineral type (carbonated hydroxylapatite) does not yield the same material properties, as revealed by Raman spectroscopy, scanning electron microscopy, electron microprobe analysis, and synchrotron X-ray diffraction analysis. Overall, the outermost enamel of a tooth has more homogeneous physical and chemical features than the rostrum. Chemical comparison of rostrum and enamel shows bioapatite in the rostrum to be enriched in Na, Mg, CO3, and S, whereas the outermost enamel shows only a slightly enriched Cl concentration. Morphologically, mineral rods (at tens of MUm scale), crystallites and prisms (at MUm and sub-MUm scale), and platelets (at tens of nm scale) all demonstrate less organized texture in the rostrum than in enamel. Such contrasts between two mineralized tissues suggest distinct pathways of biomineralization, e.g., the nature of the equilibrium between mineral and body fluid. This study illustrates the remarkable flexibility of the apatite mineral structure to match its chemical and physical properties to specific biological needs within the same animal or between species. PMID- 26552357 TI - Synthesis of (E)-oxindolylidene acetate using tandem palladium-catalyzed Heck and alkoxycarbonylation reactions. AB - Tandem reactions use consecutive reaction steps to efficiently synthesize compounds of high molecular complexity. This paper presents a tandem Pd-catalyzed Heck and alkoxycarbonylation reaction for the stereoselective synthesis of (E) oxindolylidene acetates. The mechanism underlying the Pd-catalyzed tandem reaction involves the syn-carbopalladation of ynamides followed by alkoxycarbonylation with CO and alcohol. This method makes it possible to obtain the desired (E)-configuration of oxindolylidene acetates exclusively. We evaluated the scope of the reaction by applying optimal reaction conditions to the facile synthesis of a library of (E)-oxindolylidene acetates. The resulting (E)-oxindolylidene acetates exhibited potent anticancer activities against a variety of human cancer cell lines. The anticancer activities of some (E) oxindolylidene acetates were even superior to those of known CDK inhibitors indirubin-3'-oxime and roscovitine. PMID- 26552358 TI - [Impact of the simultaneous implementation of husbandry procedures on suckling piglets]. AB - OBJECTIVE: In addition to castration, further husbandry procedures are performed in piglets during the first week of life without anaesthesia. The aim of the present study was to investigate the pain-induced stress of the husbandry procedures castration, tail docking and ear tagging performed in piglets in combination in comparison with castration or handling alone. Furthermore, the effect of the presurgical administration of the nonsteroidal anti-inflammatory drug meloxicam alone or in combination with iron was investigated. MATERIAL AND METHODS: The levels of pain and stress were evaluated based on cortisol and catecholamine concentrations, as well as from behavioural observations. The compatibility and the effect of combined drug administration were assessed, and the daily weight gain and blood iron level were determined. RESULTS: When comparing the application procedures, the slight changes observed at the iron injection site were reduced by 40% when using the mixture. After performing all three husbandry procedures without administration of meloxicam (KSO group), higher cortisol concentrations were induced for up to 4 hours compared to the handling (H) and castration (K) groups. In piglets receiving meloxicam or the mixture of iron and meloxicam presurgically, the cortisol concentration was significantly reduced for 0.5 hours after castration and up to 4 hours following all three husbandry procedures when compared to piglets without medication (groups K and KSO, respectively). CONCLUSION AND CLINICAL RELEVANCE: The results indicate that the blood cortisol concentration significantly rose due to multiple pain and distress when combining castration, ear tagging and tail docking. Application of meloxicam before performing these husbandry procedures reduced pain equally to its application before castration alone. The application of a mixed preparation of iron and meloxicam did not affect the efficacy of either drug and improved the local tolerance of the iron injection. PMID- 26552359 TI - Randomness determines practical security of BB84 quantum key distribution. AB - Unconditional security of the BB84 quantum key distribution protocol has been proved by exploiting the fundamental laws of quantum mechanics, but the practical quantum key distribution system maybe hacked by considering the imperfect state preparation and measurement respectively. Until now, different attacking schemes have been proposed by utilizing imperfect devices, but the general security analysis model against all of the practical attacking schemes has not been proposed. Here, we demonstrate that the general practical attacking schemes can be divided into the Trojan horse attack, strong randomness attack and weak randomness attack respectively. We prove security of BB84 protocol under randomness attacking models, and these results can be applied to guarantee the security of the practical quantum key distribution system. PMID- 26552361 TI - Editorial Comment on "The Interplay Between Premature Ejaculation and Erectile Dysfunction: A Systematic Review and Meta-Analysis". PMID- 26552360 TI - How to Measure Costs and Benefits of eHealth Interventions: An Overview of Methods and Frameworks. AB - Information on the costs and benefits of eHealth interventions is needed, not only to document value for money and to support decision making in the field, but also to form the basis for developing business models and to facilitate payment systems to support large-scale services. In the absence of solid evidence of its effects, key decision makers may doubt the effectiveness, which, in turn, limits investment in, and the long-term integration of, eHealth services. However, it is not realistic to conduct economic evaluations of all eHealth applications and services in all situations, so we need to be able to generalize from those we do conduct. This implies that we have to select the most appropriate methodology and data collection strategy in order to increase the transferability across evaluations. This paper aims to contribute to the understanding of how to apply economic evaluation methodology in the eHealth field. It provides a brief overview of basic health economics principles and frameworks and discusses some methodological issues and challenges in conducting cost-effectiveness analysis of eHealth interventions. Issues regarding the identification, measurement, and valuation of costs and benefits are outlined. Furthermore, this work describes the established techniques of combining costs and benefits, presents the decision rules for identifying the preferred option, and outlines approaches to data collection strategies. Issues related to transferability and complexity are also discussed. PMID- 26552362 TI - Adding value through pharmacy validation: a safety and cost perspective. AB - RATIONALE, AIMS AND OBJECTIVES: Prescribing errors (PE) are frequent, cause significant harm to patients and prove costly. Few studies demonstrate the impact of pharmacist interventions. The objectives of this study were to characterize the severity and cost of the potential outcome of PE that pharmacists can prevent and to develop an economic analysis. METHOD: We performed a non-randomized, prospective, observational study of all prescriptions made to adult patients admitted to a 1300-bed tertiary teaching hospital in Madrid (Spain) by means of a computerized physician order entry tool combined with a clinical decision support system. We analysed PE intercepted through the pharmacist validation process between January and June 2013. An independent team determined the severity of the potential adverse drug event (ADE) and the probability of causing an ADE (PAE). We estimated the cost avoidance and performed an economic analysis. A kappa statistic was used to verify inter-observer agreement. RESULTS: 484 PE were intercepted: 36.2% of PE were classified as being of minor severity, 59.1% as moderate and 4.7% as serious. The most common type of moderate-serious PE found was excessive dose (30%, 94/309), followed by insufficient dose (20%, 62/309), and omission (19%, 58/309). The most frequent families of drugs involved in moderate-serious PE were antineoplastic agents (22.3%, 69/309) and antimicrobials (17.2%, 53/309). The PAE was higher than 40% in 49% of PE. We estimated a cost avoidance of ?291,422 and a return on investment of ?1.7 for each ?1 spent on a pharmacist's salary. The overall inter-rater agreement for the participants was moderate for severity (kappa = 0.57; P <0.005) and strong for the PAE (kappa = 0.77; P <0.005). CONCLUSIONS: Pharmacists add important value in preventing PE, and their interventions are financially beneficial for the institution. PMID- 26552363 TI - Two cases of amoxycillin-induced follicular acute localised exanthematous pustulosis. AB - We report two cases of Caucasian women who developed folliculocentric pustulosis after exposure to amoxycillin. A literature review found that most amoxycillin related pustular eruptions were reported as acute generalised exanthematous pustulosis (AGEP) or acute localised exanthematous pustulosis (ALEP). Histopathology from both our cases showed sterile suppurative folliculitis, which resolved on the cessation of amoxycillin. PMID- 26552364 TI - VvpE mediates the intestinal colonization of Vibrio vulnificus by the disruption of tight junctions. AB - The disruption of gastrointestinal tight junctions and their colonization evoked by enteric pathogens are hallmarks of the pathogenesis. Vibrio (V.) vulnificus, VvpE, is an elastase which is responsible for host surface adherence and vascular permeability; however, the functional roles of VvpE in the pathogenesis of V. vulnificus (WT) are poorly understood. In the present study, we have investigated the role of VvpE in regulation of intestinal tight junctions and the colonization of WT. We found that mutation of the vvpE gene from V. vulnificus (vvpE mutant) prevents intestinal tight/adherens junction dysregulation due to a WT infection and maintains the physiological level of the epithelial paracellular permeability. Interestingly, the vvpE mutant exhibited defective intestinal colonization abilities, whereas WT colonization was significantly elevated in the ileum in a time-dependent manner. Finally, the vvpE mutant negated the enterotoxicity, the breakdown of red blood cells, and pro-inflammatory responses, all of which are induced by the WT infection. In addition, the results of a LC MS/MS analysis showed that VvpE contributes to WT pathogenesis in multiple ways by interacting with intestinal proteins, including beta-globin, Annexin A2, Annexin A4, F-actin, and intelectin-1b. These results demonstrate that VvpE plays important role in promoting the tight junction disruption and intestinal colonization of V. vulnificus and that it also has the ability to interact with the intestinal proteins responsible for microbial pathogenesis. PMID- 26552365 TI - Synthesis, characterization, and electronic structures of a methyl germyliumylidene ion and germylone-group VI metal complexes. AB - The reaction of germylone (L)Ge (1) [L = 3-Ad-1-{C((t)Bu) = N(Mes)}C3H4N2] with 1 equivalent of MeOTf afforded a germyliumylidene ion [(L)GeMe](+)OTf(-) (2), while reactions with M(CO)5(thf) (M = Cr, Mo, W) gave the corresponding germylone-metal complexes [(L)Ge]M(CO)5 (3-5). The former possesses a pyramidal Ge center, whereas the latter display a planar geometry around the Ge atom. Computational studies showed a unique bonding interaction between 1 and the M(CO)5 unit, which involves a sigma-donation as well as a weak pi-back-donation. PMID- 26552366 TI - Protein C-terminal enzymatic labeling identifies novel caspase cleavages during the apoptosis of multiple myeloma cells induced by kinase inhibition. AB - Caspase activation and proteolytic cleavages are the major events in the early stage of apoptosis. Identification of protein substrates cleaved by caspases will reveal the occurrence of the early events in the apoptotic process and may provide potential drug targets for cancer therapy. Although several N-terminal MS based proteomic approaches have been developed to identify proteolytic cleavages, these methods have their inherent drawbacks. Here we apply a previously developed proteomic approach, protein C-terminal enzymatic labeling (ProC-TEL), to identify caspase cleavage events occurring in the early stage of the apoptosis of a myeloma cell line induced by kinase inhibition. Both previously identified and novel caspase cleavage sites are detected and the reduction of the expression level of several proteins is confirmed biochemically upon kinase inhibition although the current ProC-TEL procedure is not fully optimized to provide peptide identifications comparable to N-terminal labeling approaches. The identified cleaved proteins form a complex interaction network with central hubs determining morphological changes during the apoptosis. Sequence analyses show that some ProC TEL identified caspase cleavage events are unidentifiable when traditional N terminomic approaches are utilized. This work demonstrates that ProC-TEL is a complementary approach to the N-terminomics for the identification of proteolytic cleavage events such as caspase cleavages in signaling pathways. PMID- 26552367 TI - Factors associated with eating performance for long-term care residents with moderate-to-severe cognitive impairment. AB - AIMS: The aim of this study was to examine the association of specific personal and environmental factors with eating performance among long-term care residents with moderate-to-severe cognitive impairment. BACKGROUND: Eating is the one of the most basic and easiest activities of daily living to perform. While multilevel factors can be associated with eating performance, the evidence among those with dementia was insufficient. DESIGN: A secondary analysis of baseline data collected between March and September in 2012 from 199 residents in eight long-term care facilities. METHODS: Eating performance was conceptualized using the single self-care 'feeding' item in the Barthel Index and was scored based on four levels of dependence and assistance required. Binary logistic regression was used to examine the adjusted association of specific factors with eating performance. RESULTS: Almost one-third of the residents needed help with eating. After adjusting the type of facility, number of comorbidities, chair-sitting balance, agitation and depression, compromised eating performance was associated with severe cognitive impairment and low physical capability. CONCLUSION: This study supported the association of eating performance with cognitive impairment and physical capability among long-term care residents with moderate-to-severe cognitive impairment. Targeted interventions should be implemented to reduce the impact of cognitive decline on eating performance and promote physical capability to optimize eating performance. Future work need to use validated multiple-item measures for eating performance and test the association of personal and environmental factors with eating performance among a larger heterogeneous group of long-term care residents to enhance understanding of the factors. PMID- 26552369 TI - Predictive value of urinary interleukin-6 for symptomatic urinary tract infections in a nursing home population. AB - OBJECTIVES: To study urinary interleukin-6, interleukin-8 and pyuria during episodes of asymptomatic bacteriuria and symptomatic urinary tract infection in the institutionalized elderly, and to investigate the role of interleukin-6 as a biomarker for differential diagnosis. METHODS: Levels of interleukin-6, interleukin-8 and pyuria were assessed in 35 older adults with asymptomatic bacteriuria and symptomatic urinary tract infection to define possible diagnostic thresholds. In a two-phase intervention study, the antibiotic treatment for urinary tract infection before and after introduction of urinary interleukin-6 as a biomarker was then assessed. RESULTS: Asymptomatic bacteriuria patients had no or low levels of interleukin-6, and low levels of interleukin-8 and pyuria. Women had lower interleukin-6 and interleukin-8 than men (P = 0.05). Interleukin-6 was the only marker showing significant increases during urinary tract infection episodes in patients with both asymptomatic bacteriuria and urinary tract infection, in pooled (P = 0.042) and in paired intra-individual (P = 0.017) comparisons. In the intervention study lectures, the increased use of urine cultures and the introduction of interleukin-6 as a biomarker reduced antibiotic treatments by 20%. Antibiotic-treated urinary tract infection episodes had increased interleukin-6 as compared with urinary tract infection episodes not treated (P = 0.02), and as compared with asymptomatic bacteriuria patients (P < 0.0001). The sensitivity and specificity of interleukin-6 (cut-off 25 pg/mL) differentiating asymptomatic bacteriuria from urinary tract infection was 57% and 80%, respectively. CONCLUSIONS: Urinary interleukin-6 shows promise as a biomarker to detect the transition from asymptomatic bacteriuria to symptomatic urinary tract infection in older adults. Further larger studies with robust methodology are warranted to determine whether development for near to patient testing would be worthwhile. PMID- 26552368 TI - Resveratrol inhibits epithelial-mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy. AB - Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and ocular trauma, and its recurrence may lead to irreversible vision loss. Epithelial to mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a critical step in the pathogenesis of PVR, which is characterized by fibrotic membrane formation and traction retinal detachment. In this study, we investigated the potential impact of resveratrol (RESV) on EMT and the fibrotic process in cultured RPE cells and further examined the preventive effect of RESV on PVR development using a rabbit model of PVR. We found that RESV induces mesenchymal to epithelial transition (MET) and inhibits transforming growth factor-beta2(TGF-beta2)-induced EMT of RPE cells by deacetylating SMAD4. The effect of RESV on MET was dependent on sirtuin1 activation. RESV suppressed proliferation, migration and fibronectin synthesis induced by platelet-derived growth factor-BB or TGF-beta2. In vivo, RESV inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that RESV reduced fibrotic membrane formation and decreased alpha-SMA expression in the epiretinal membranes. These results suggest the potential use of RESV as a therapeutic agent to prevent the development of PVR by targeting EMT of RPE. PMID- 26552370 TI - Atrial Overdrive Pacing: Is VA Linking Present? PMID- 26552371 TI - Cross-sectional study of the association between functional status and acute kidney injury in geriatric patients. AB - BACKGROUND: Patients with chronic kidney disease tend to have impaired functional status, and this can increase the risk of morbidity and mortality. However, no previous studies have rigorously evaluated the relationship between incident acute kidney injury (AKI) and functional status of elderly patients. METHODS: Elderly patients (>= 65 years-old) were prospectively from the general medical wards of a single medical center in Taiwan between January, 2014 and August, 2014. These patients were divided into those with and without AKI at initial presentation, according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Functional status was assessed by Barthel Index on admission. Multiple regression analyses were utilized to investigate the relationship between AKI and functional status. RESULTS: One hundred and fifty-two elderly patients were recruited, 38.9 % of whom had AKI. Patients with AKI at admission had significantly higher mean Charlson Comorbidity Index score (p = 0.05) and borderline lower mean Barthel Index score (34.5 vs. 43.1; p = 0.08), and a significantly lower bladder continence subscale (5.4 vs. 7.0; p = 0.05). Multiple regression analyses indicated that the presence of AKI at admission was associated with a significantly lower Barthel Index score (p = 0.04). Increasing AKI severity (higher KDIGO stage) was also associated with significantly lower Barthel Index score (p < 0.01). CONCLUSIONS: This study documented a close relationship between AKI and functional status in the elderly. Interventions that aim to restore functional status might help to lower the risk of AKI in the elderly. PMID- 26552372 TI - The WRKY transcription factor family and senescence in switchgrass. AB - BACKGROUND: Early aerial senescence in switchgrass (Panicum virgatum) can significantly limit biomass yields. WRKY transcription factors that can regulate senescence could be used to reprogram senescence and enhance biomass yields. METHODS: All potential WRKY genes present in the version 1.0 of the switchgrass genome were identified and curated using manual and bioinformatic methods. Expression profiles of WRKY genes in switchgrass flag leaf RNA-Seq datasets were analyzed using clustering and network analyses tools to identify both WRKY and WRKY-associated gene co-expression networks during leaf development and senescence onset. RESULTS: We identified 240 switchgrass WRKY genes including members of the RW5 and RW6 families of resistance proteins. Weighted gene co expression network analysis of the flag leaf transcriptomes across development readily separated clusters of co-expressed genes into thirteen modules. A visualization highlighted separation of modules associated with the early and senescence-onset phases of flag leaf growth. The senescence-associated module contained 3000 genes including 23 WRKYs. Putative promoter regions of senescence associated WRKY genes contained several cis-element-like sequences suggestive of responsiveness to both senescence and stress signaling pathways. A phylogenetic comparison of senescence-associated WRKY genes from switchgrass flag leaf with senescence-associated WRKY genes from other plants revealed notable hotspots in Group I, IIb, and IIe of the phylogenetic tree. CONCLUSIONS: We have identified and named 240 WRKY genes in the switchgrass genome. Twenty three of these genes show elevated mRNA levels during the onset of flag leaf senescence. Eleven of the WRKY genes were found in hotspots of related senescence-associated genes from multiple species and thus represent promising targets for future switchgrass genetic improvement. Overall, individual WRKY gene expression profiles could be readily linked to developmental stages of flag leaves. PMID- 26552373 TI - The functionality of the gastrointestinal microbiome in non-human animals. AB - Due to the significance of the microbiome on human health, much of the current data available regarding microbiome functionality is centered on human medicine. For agriculturally important taxa, the functionality of gastrointestinal bacteria has been studied with the primary goals of improving animal health and production performance. With respect to cattle, the digestive functions of bacteria in cattle are unarguably critical to digestion and positively impact production performance. Conversely, some research suggests that the gastrointestinal microbiome in chickens competes with the host for nutrients and produces toxins that can harm the host resulting in decreased growth efficiency. Concerning many other species including reptiles and cetaceans, some cataloging of fecal bacteria has been conducted, but the functionality within the host remains ambiguous. These taxa could provide interesting gastrointestinal insight into functionality and symbiosis considering the extreme feeding regimes (snakes), highly specialized diets (vampire bats), and living environments (polar bears), which warrants further exploration. PMID- 26552374 TI - Actinoplanes lichenis sp. nov., isolated from lichen. AB - A novel species of the genus Actinoplanes, strain LDG1-22T, for which we propose the name Actinoplanes lichenis sp. nov., was isolated from a lichen sample collected from tree bark in Thailand. The taxonomic position of the species has been described based on a polyphasic approach. Strain LDG1-22T produced irregular sporangia on agar media. It contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major menaquinone was MK-9(H4); the polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and phosphatidylglycerol. Whole-cell hydrolysates contained ribose, glucose, mannose and small amounts of arabinose and xylose. The major cellular fatty acids were anteiso-C15 : 0 (31.2 %) and iso-C16 : 0 (14.2 %). Mycolic acids were absent. The G+C content was 73.6 %. 16S rRNA gene sequence analysis of strain LDG1-22T showed highest similarity (98.8 %) to Actinoplanes friuliensis DSM 45797T and it clustered with Actinoplanes nipponensis JCM 3264T and Actinoplanes missouriensis JCM 3121T in phylogenetic tree analysis. On the basis of the phenotypic characteristics and DNA-DNA relatedness, strain LDG1-22T could be distinguished from related species of the genus Actinoplanes and so represents a novel species of this genus. The type strain of Actinoplanes lichenis sp. nov. is LDG1-22T ( = JCM 30485T = TISTR 2343T = PCU 344T). PMID- 26552375 TI - Equity in access to health care among asylum seekers in Germany: evidence from an exploratory population-based cross-sectional study. AB - BACKGROUND: Research on inequities in access to health care among asylum-seekers has focused on disparities between asylum-seekers and resident populations, but little attention has been paid to potential inequities in access to care within the group of asylum-seekers. We aimed to analyse the principles of horizontal equity (i.e., equal access for equal need irrespective of socioeconomic status, SES) and vertical equity (higher allocation of resources to those with higher need) among asylum-seekers in Germany. METHODS: We performed a secondary exploratory analysis on cross-sectional data obtained from a population-based questionnaire survey among all asylum-seekers (aged 18 or above) registered in three administrative districts in Germany during the three-month study period (N = 1017). Data were collected on health care access (health care utilisation of four types of services and unmet medical need), health care need (approximated by sex, age and self-rated health status), and SES (highest educational attainment and subjective social status, SSS). We calculated odds ratios and 95% confidence intervals (CI) in multiple logistic regression models to analyse associations between SES indicators and access to health care under control of need. RESULTS: We contacted 60.4% (614) of the total asylum-seekers population, of which 25.4% (N = 156) participated in the study. Educational attainment showed no significant effect on health care access in crude models, but was positively associated with utilisation of psychotherapists and hospital admissions in adjusted models. Higher SSS was positively associated with health care utilisation of all types of services. The odds of hospitals admissions for asylum-seekers in the medium and highest SSS category were 3.18 times [1.06, 9.59] and 1.6 times [0.49, 5.23] the odds of those in the lowest SSS category. After controlling for need variables none of the SES indicators were significantly associated with measures of access to care, but a positive association remained, indicating higher utilisation of health care among asylum-seekers with higher SES. Age, sex or general health status were the only significant predictors of health care utilisation in fully adjusted models. The adjusted odds of reporting unmet medical needs among asylum seekers with "fair/bad/very bad" health status were 2.16 times [0.84, 5.59] the odds of those with "good/very good" health status. CONCLUSION: Our findings revealed that utilisation of health services among asylum-seekers is associated with higher need (vertical equity met). Horizontal equity was met with respect to educational attainment for most outcomes, but a social gradient in health care utilisation was observed across SSS. Further confirmatory research is needed, especially on potential inequities in unmet medical need and on measurements of SES among asylum-seekers. PMID- 26552376 TI - Awareness of preventive medication among women at high risk for breast cancer and their willingness to consider transdermal or oral tamoxifen: a focus group study. AB - BACKGROUND: Despite demonstrated efficacy, acceptance of selective estrogen receptor modulators (SERMs), such as tamoxifen, for breast cancer risk reduction remains low. Delivering SERMs via local transdermal therapy (LTT) could significantly reduce systemic effects and therefore may increase acceptance. We aim to assess women's knowledge of breast cancer prevention medications and views on LTT of SERMs. METHODS: Focus groups were conducted with healthy women identified through the comprehensive breast center of a large urban cancer institution. Group discussions covered risk perceptions, knowledge of and concerns about risk reducing medications. Participants reported their perceived risk for breast cancer (average, below/above average), preference for SERMs in a pill or gel form, risk factors, and prior physician recommendations regarding risk-reducing medicines. Participants' breast cancer risk was estimated using tools based on the Gail Model. Trained personnel examined all qualitative results systematically; risk perceptions and preferred method of medication delivery were tallied quantitatively. RESULTS: Four focus groups (N = 32) were conducted. Most participants had at least a college degree (78.2 %) and were of European (50 %) or African ancestry (31 %). The majority (72 %) were at elevated risk for breast cancer; approximately half of these women perceived themselves to be at elevated risk. Few participants had prior knowledge of preventive medications. The women noted a number of concerns about LTT, including dosage, impact on day-to-day life, and side effects; nonetheless, over 90 % of the women stated they would prefer LTT to a pill. CONCLUSION: Awareness of preventive medications was low even in a highly educated sample of high-risk women. If given a choice in the route of administration, most women preferred a gel to a pill, anticipating fewer side effects. Future work should focus on demonstrating equivalent efficacy and reduced toxicity of topical over oral medications and on raising awareness of chemopreventive options for breast cancer. PMID- 26552377 TI - Social huddling and physiological thermoregulation are related to melanism in the nocturnal barn owl. AB - Endothermic animals vary in their physiological ability to maintain a constant body temperature. Since melanin-based coloration is related to thermoregulation and energy homeostasis, we predict that dark and pale melanic individuals adopt different behaviours to regulate their body temperature. Young animals are particularly sensitive to a decrease in ambient temperature because their physiological system is not yet mature and growth may be traded-off against thermoregulation. To reduce energy loss, offspring huddle during periods of cold weather. We investigated in nestling barn owls (Tyto alba) whether body temperature, oxygen consumption and huddling were associated with melanin-based coloration. Isolated owlets displaying more black feather spots had a lower body temperature and consumed more oxygen than those with fewer black spots. This suggests that highly melanic individuals display a different thermoregulation strategy. This interpretation is also supported by the finding that, at relatively low ambient temperature, owlets displaying more black spots huddled more rapidly and more often than those displaying fewer spots. Assuming that spot number is associated with the ability to thermoregulate not only in Swiss barn owls but also in other Tytonidae, our results could explain geographic variation in the degree of melanism. Indeed, in the northern hemisphere, barn owls and allies are less spotted polewards than close to the equator, and in the northern American continent, barn owls are also less spotted in colder regions. If melanic spots themselves helped thermoregulation, we would have expected the opposite results. We therefore suggest that some melanogenic genes pleiotropically regulate thermoregulatory processes. PMID- 26552378 TI - Higher photosynthetic capacity and different functional trait scaling relationships in erect bryophytes compared with prostrate species. AB - Ecophysiological studies of bryophytes have generally been conducted at the shoot or canopy scale. However, their growth forms are diverse, and knowledge of whether bryophytes with different shoot structures have different functional trait levels and scaling relationships is limited. We collected 27 bryophyte species and categorised them into two groups based on their growth forms: erect and prostrate species. Twenty-one morphological, nutrient and photosynthetic traits were quantified. Trait levels and bivariate trait scaling relationships across species were compared between the two groups. The two groups had similar mean values for shoot mass per area (SMA), light saturation point and mass-based nitrogen (N(mass)) and phosphorus concentrations. Erect bryophytes possessed higher values for mass-based chlorophyll concentration (Chl(mass)), light saturated assimilation rate (A(mass)) and photosynthetic nitrogen/phosphorus use efficiency. N(mass), Chl(mass) and A(mass) were positively related, and these traits were negatively associated with SMA. Furthermore, the slope of the regression of N(mass) versus Chl(mass) was steeper for erect bryophytes than that for prostrate bryophytes, whereas this pattern was reversed for the relationship between Chl(mass) and A(mass). In conclusion, erect bryophytes possess higher photosynthetic capacities than prostrate species. Furthermore, erect bryophytes invest more nitrogen in chloroplast pigments to improve their light-harvesting ability, while the structure of prostrate species permits more efficient light capture. This study confirms the effect of growth form on the functional trait levels and scaling relationships of bryophytes. It also suggests that bryophytes could be good models for investigating the carbon economy and nutrient allocation of plants at the shoot rather than the leaf scale. PMID- 26552379 TI - Beyond body mass: how prey traits improve predictions of functional response parameters. AB - Understanding the factors that determine the strength of predator-prey interactions is essential to understanding community structure and stability. Variation in the strength of predator-prey interactions often can be attributed to predator mass and prey mass, or abiotic factors like temperature. However, even when accounting for these factors, there remains a considerable amount of unexplained variation that may be attributed to other traits. We compiled functional response data from the literature to investigate how predator mass, prey mass, prey type (taxonomic identity), temperature, and prey defenses (hard vs soft integument) contributed to the variation found in the predator-prey interactions between freshwater cyclopoid copepods and their prey. Surprisingly, our results indicate that prey identity (taxonomic group) and defenses (hard vs soft integument) are more important for generating variation in interaction strengths than body mass and temperature. This suggests that allometric functions can only take us so far when attempting to better understand variation in individual predator prey interactions, and that we must evaluate how other traits influence interaction strengths. Identifying additional factors such as prey defenses may enable us to better predict potential changes in the structure and function of planktonic and other food webs by better accounting for the variation in the interactions between generalists and their many prey types. PMID- 26552380 TI - Floral traits and pollination ecology of European Arum hybrids. AB - Hybridisation is common in plants and can affect the genetic diversity and ecology of sympatric parental populations. Hybrids may resemble the parental species in their ecology, leading to competition and/or gene introgression; alternatively, they may diverge from the parental phenotypes, possibly leading to the colonisation of new ecological niches and to speciation. Here, we describe inflorescence morphology, ploidy levels, pollinator attractive scents, and pollinator guilds of natural hybrids of Arum italicum and A. maculatum (Araceae) from a site with sympatric parental populations in southern France to determine how these traits affect the hybrid pollination ecology. Hybrids were characterised by inflorescences with a size and a number of flowers more similar to A. italicum than to A. maculatum. In most cases, hybrid stamens were purple, as in A. maculatum, and spadix appendices yellow, as in A. italicum. Hybrid floral scent was closer to that of A. italicum, but shared some compounds with A. maculatum and comprised unique compounds. Also, the pollinator guild of the hybrids was similar to that of A. italicum. Nevertheless, the hybrids attracted a high proportion of individuals of the main pollinator of A. maculatum. We discuss the effects of hybridisation in sympatric parental zones in which hybrids exhibit low levels of reproductive success, the establishment of reproductive barriers between parental species, the role of the composition of floral attractive scents in the differential attraction of pollinators and in the competition between hybrids and their parental species, and the potential of hybridisation to give rise to new independent lineages. PMID- 26552381 TI - Intraspecific scaling in frog calls: the interplay of temperature, body size and metabolic condition. AB - Understanding physiological and environmental determinants of strategies of reproductive allocation is a pivotal aim in biology. Because of their high metabolic cost, properties of sexual acoustic signals may correlate with body size, temperature, and an individual's energetic state. A quantitative theory of acoustic communication, based on the metabolic scaling with temperature and mass, was recently proposed, adding to the well-reported empirical patterns. It provides quantitative predictions for frequencies, call rate, and durations. Here, we analysed the mass, temperature, and body condition scaling of spectral and temporal attributes of the advertisement call of the treefrog Hypsiboas pulchellus. Mass dependence of call frequency followed metabolic expectations (f~M (-0.25), where f is frequency and M is mass) although non-metabolic allometry could also account for the observed pattern. Temporal variables scaled inversely with mass contradicting metabolic expectations (d~M (0.25), where d is duration), supporting instead empirical patterns reported to date. Temperature was positively associated with call rate and negatively with temporal variables, which is congruent with metabolic predictions. We found no significant association between temperature and frequencies, adding to the bulk of empirical evidence. Finally, a result of particular relevance was that body condition consistently determined call characteristics, in interaction with temperature or mass. Our intraspecific study highlights that even if proximate determinants of call variability are rather well understood, the mechanisms through which they operate are proving to be more complex than previously thought. The determinants of call characteristics emerge as a key topic of research in behavioural and physiological biology, with several clear points under debate which need to be analysed on theoretical and empirical grounds. PMID- 26552382 TI - Erratum to: A spectrum of intracranial vascular high-flow arteriovenous shunts in RASA1 mutations. AB - Erratum to: Childs Nerv Syst DOI 10.1007/s00381-015-2940-y. Unfortunately, one of the authors' name was misspelled in the original publication of this article. Instead of Micheal Soderman, it should have been Michael Soderman. PMID- 26552383 TI - Selective dorsal rhizotomy as an alternative to intrathecal baclofen pump replacement in GMFCS grades 4 and 5 children. AB - BACKGROUND: Conventionally, selective dorsal rhizotomy (SDR) has been reserved for ambulant children and implantation of intrathecal baclofen (ITB) pump for non ambulant children with cerebral palsy. Rather than replacing the ITB pump in selected Gross Motor Function Classification System (GMFCS) grades 4 and 5 children, we elected to undertake SDR instead. We discuss the rationale and outcomes. OBJECTIVES: To assess if children with severe spasticity treated with long-term ITB pump would benefit from SDR as alternative procedure to replacement of ITB pump. METHOD: This study is a prospective review of ten children with severe spasticity. Indications for ITB pump replacement in 3/10 children were previous ITB pump infection and the remaining seven were nearing depletion of drug delivery system. Pre- and post-SDR mean modified Ashworth scores, assessment of urological function and survey of parent/carer satisfaction were undertaken. RESULT: Mean Ashworth score reductions post-SDR in the lower limbs and upper limbs were 2.4 and 1.70, respectively. An improvement in urological function was also noticed in 27% of patients. Overall, 90% of parents/carers felt that functional outcome with SDR was improved compared with that of ITB. CONCLUSION: SDR in comparison to ITB in this subgroup is cheaper, less intrusive by avoiding refills/replacement and found to be more effective than ITB in reducing spasticity and providing ease for nursing care. We therefore suggest that consideration should be given to SDR as an alternative in patients previously implanted with ITB systems complicated by infection or nearing end of battery life. PMID- 26552384 TI - Congenital subaxial cervical subluxation presenting as a bilateral Erb's palsy: surgical management, rehabilitation, and outcome. AB - INTRODUCTION: Subaxial spine injuries during infancy are uncommon. CASE REPORT: We present the case of an infant referred to our brachial plexus clinic with proximal weakness of both arms noted immediately following a complicated breech delivery. Nerve conduction studies were consistent with bilateral proximal upper plexus injury; however, radiological evaluation revealed a C4-C5 subluxation and MRI features of bilateral C5 root avulsions. He was immobilized in a cervical body orthosis and underwent open reduction and posterior C4-C5-C6 fixation at 10 weeks age using luque rods, sublaminar wires, and rib graft. The spine was immobilized in a custom molded cervicothoracic brace for a total of 3 months, and a home exercise program prescribed. Follow-up radiographic evaluation showed good posterior bony fusion by 2 months but persistent bilateral proximal upper limb weakness with reduced compound motor action potential (CMAP) amplitudes of the axillary and musculocutaneous nerves. Bilateral supraclavicular exploration and C5 root neurotization using the ipsilateral C7 nerve roots were performed at 7 months of age. Voluntary biceps activity followed by voluntary external rotation with gravity eliminated was noted within the next 2-3 months. He progressed to develop near normal motor control of bilateral upper limbs within 1 year. CONCLUSIONS: We wish to report this rare entity and our favorable outcome using a strategy of early spinal stabilization and neurotization repair to restore function following proximal nerve root injury. PMID- 26552385 TI - Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex. AB - PURPOSE: The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging. METHODS: This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging. RESULTS: While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p < 0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p = 0.658). Significant tumor growth was observed in children (p = 0.012) and adults (p = 0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18-40 months and median for adults 23 months, interquartile range 12-34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p = 0.03). CONCLUSIONS: The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities. PMID- 26552386 TI - Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat. AB - BACKGROUND: Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. METHODS: Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography. RESULTS: Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae. CONCLUSIONS: These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar fusion. PMID- 26552387 TI - Progress toward malaria elimination in Jazan Province, Kingdom of Saudi Arabia: 2000-2014. AB - BACKGROUND: The draft Global Technical Strategy for malaria aims to eliminate malaria from at least 10 countries by 2020. Yemen and Saudi Arabia remain the last two countries on the Arabian Peninsula yet to achieve elimination. Over the last 50 years, systematic efforts to control malaria in the Kingdom of Saudi Arabia has successfully reduced malaria cases to a point where malaria is now constrained largely to Jazan Province, the most south-western area along the Red Sea. The progress toward elimination in this province is reviewed between 2000 and 2014. METHODS: Data were obtained from the Ministry of Health case-reporting systems, activity reports, unpublished consultants reports, and relevant scientific published papers. Sub-provincial population data were obtained the national household censuses undertaken in 2004 and 2010. Rainfall data were obtained from the Meteorological Department in Jazan. RESULTS: Between 2000 and 2014 there were 5522 locally acquired cases of malaria and 9936 cases of imported malaria. A significant reduction in locally acquired malaria cases was observed from 2000 to 2014, resulting in an average annual incidence (2010-2014) of 0.3 cases per 10,000 population. Conversely imported cases, since 2000, remain consistent and higher than locally acquired cases, averaging between 250 and 830 cases per year. The incidence of locally acquired cases is heterogeneous across the Province, with only a few health districts contributing the majority of the cases. The overall decline in malaria case incidence can be attributed to coincidental expansion of control efforts and periods of exceptionally low rainfall. CONCLUSIONS: Jazan province is poised to achieve malaria elimination. There is a need to change from a policy of passive case detection to reactively and proactively detecting infectious reservoirs that require new approaches to surveillance. These should be combined with advanced epidemiological tools to improve the definitions of epidemiological receptive and hotspot malaria risk mapping. The single largest threat currently remains the risks posed by imported infections from Yemen. PMID- 26552388 TI - Distance-of-Flight Mass Spectrometry with IonCCD Detection and an Inductively Coupled Plasma Source. AB - Distance-of-flight mass spectrometry (DOFMS) is demonstrated for the first time with a commercially available ion detector-the IonCCD camera. Because DOFMS is a velocity-based MS technique that provides spatially dispersive, simultaneous mass spectrometry, a position-sensitive ion detector is needed for mass-spectral collection. The IonCCD camera is a 5.1-cm long, 1-D array that is capable of simultaneous, multichannel ion detection along a focal plane, which makes it an attractive option for DOFMS. In the current study, the IonCCD camera is evaluated for DOFMS with an inductively coupled plasma (ICP) ionization source over a relatively short field-free mass-separation distance of 25.3-30.4 cm. The combination of ICP-DOFMS and the IonCCD detector results in a mass-spectral resolving power (FWHM) of approximately 900 and isotope-ratio precision equivalent to or slightly better than current ICP-TOFMS systems. The measured isotope-ratio precision in % relative standard deviation (%RSD) was >=0.008%RSD for nonconsecutive isotopes at 10-ppm concentration (near the ion-signal saturation point) and >=0.02%RSD for all isotopes at 1-ppm. Results of DOFMS with the IonCCD camera are also compared with those of two previously characterized detection setups. PMID- 26552390 TI - Of prime ministers, presidents and professors. PMID- 26552389 TI - Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping. AB - Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain disulfide bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter and intra-molecular disulfide bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the sulfur atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between cysteine-containing peptides and peptides lacking sulfur. High sulfur content in a peptide decreases the normalized nominal mass defect (NMD) and increases the normalized isotopic shift (NIS). Hence in a 3D plot of mass, NIS, and NMD, peptides with sulfur appear in this plot with a distinct spatial localization compared with peptides that lack sulfur. In this study we investigated the skin secretion of two frog species; Odorrana schmackeri and Bombina variegata. Peptides from the crude skin secretions were separated by nanoflow LC, and of all eluting peptides high resolution zoom scans were acquired in order to accurately determine both monoisotopic mass and average mass. Both the NMD and the NIS were calculated from the experimental data using an in-house developed MATLAB script. Candidate peptides exhibiting a low NMD and high NIS values were selected for targeted de novo sequencing, and this resulted in the identification of several novel inter- and intra-molecular disulfide bond containing peptides. Graphical Abstract ?. PMID- 26552391 TI - Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging. AB - BACKGROUND: Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity. OBJECTIVE: To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing99mTcdisida, 99mTc-phytate and 99mTc-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats. METHOD: Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for 99mTc-phytate, 99mTc-sestamibi and 99mTc-disida extraction, respectively. RESULTS: Control (L/BM= 98+/-3; H/B=2.3+/-0.4; Tmax=8+/ 3), DOX (L/BM: 85+/-3, 80+/-3; H/B, 3.5+/-0.5, 3.3+/-0.5 and Tmax 6+/-1, 4+/-1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99+/-0.3, 98+/-1; H/B 2.9+/ 0.5, 2.9+/-0.5 and Tmax, 8+/-2, 9+/-2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin. CONCLUSION: Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin. PMID- 26552392 TI - Nano-Hydroxyapatite Doped with Ho-166 as Drug Delivery System for Bone Cancer Therapy and Diagnosis: Developing a Theragnostic Radiopharmaceuticals. AB - BACKGROUND: The use of nanobiomaterials is increasing each day. Among the immense variety of nanomaterials developed and studied the hydroxyapatite is one of the most ones. OBJECTIVE: In this study we developed and tested nano-hydroxyapatite dopped with Ho-166 for bone cancer. RESULTS: The results showed that the nano hydroxyapatite dopped with Ho-166 has a great affinity for the bone. CONCLUSION: The pre-clinical studies support the use as a nano-radiopharmaceuticals for bone cancer treatment and diagnosis. PMID- 26552393 TI - Listeria monocytogenes associated kerato-conjunctivitis in four horses in Norway. AB - Listeria monocytogenes has been reported to cause various infectious diseases in both humans and animals. More rarely, ocular infections have been reported. To our knowledge, only two cases of Listeria keratitis have been described in horses. We report kerato-conjunctivitis in four Norwegian horses associated with L. monocytogenes. Clinically, all cases were presented with recurrent unilateral kerato-conjunctivitis. L. monocytogenes bacteria were isolated from swab samples from all cases, and cytology carried out in 3 cases was indicative of L. monocytogenes infection. The present report describes the first known cases in which L. monocytogenes has been isolated from keratitic lesions in horses in Norway. A potential risk factor may be feeding of silage or haylage, but other sources of infection cannot be ruled out. The phenotypic features including antimicrobial susceptibility and serotype of the isolates are described. Laboratory detection of L. monocytogenes demands extra caution since only low numbers of bacteria were detected in the eye-swabs, probably due to the low volume of sample material and the intracellular niche of the bacterium. A general poor response to treatment in all these cases indicates that clinicians should pay extra attention to intensity and duration of treatment if L. monocytogenes is identified in connection with equine kerato-conjunctivitis. PMID- 26552394 TI - Some Like it High! Phylogenetic Diversity of High-Elevation Cyanobacterial Community from Biological Soil Crusts of Western Himalaya. AB - The environment of high-altitudinal cold deserts of Western Himalaya is characterized by extensive development of biological soil crusts, with cyanobacteria as dominant component. The knowledge of their taxonomic composition and dependency on soil chemistry and elevation is still fragmentary. We studied the abundance and the phylogenetic diversity of the culturable cyanobacteria and eukaryotic microalgae in soil crusts along altitudinal gradients (4600-5900 m) at two sites in the dry mountains of Ladakh (SW Tibetan Plateau and Eastern Karakoram), using both microscopic and molecular approaches. The effects of environmental factors (altitude, mountain range, and soil physico-chemical parameters) on the composition and biovolume of phototrophs were tested by multivariate redundancy analysis and variance partitioning. Both phylogenetic diversity and composition of morphotypes were similar between Karakorum and Tibetan Plateau. Phylogenetic analysis of 16S rRNA gene revealed strains belonging to at least five genera. Besides clusters of common soil genera, e.g., Microcoleus, Nodosilinea, or Nostoc, two distinct clades of simple trichal taxa were newly discovered. The most abundant cyanobacterial orders were Oscillatoriales and Nostacales, whose biovolume increased with increasing elevation, while that of Chroococales decreased. Cyanobacterial species richness was low in that only 15 morphotypes were detected. The environmental factors accounted for 52 % of the total variability in microbial data, 38.7 % of which was explained solely by soil chemical properties, 14.5 % by altitude, and 8.4 % by mountain range. The elevation, soil phosphate, and magnesium were the most important predictors of soil phototrophic communities in both mountain ranges despite their different bedrocks and origin. The present investigation represents a first record on phylogenetic diversity of the cyanobacterial community of biological soil crusts from Western Himalayas and first record from altitudes over 5000 m. PMID- 26552395 TI - High Bacterial Diversity and Phylogenetic Novelty in Dark Euxinic Freshwaters Analyzed by 16S Tag Community Profiling. AB - Microbial communities growing under extreme low redox conditions are present in anoxic and sulfide-rich (euxinic) environments such as karstic lakes and experience limitation of electron acceptors. The fine natural chemical gradients and the large diversity of organic and inorganic compounds accumulated in bottom waters are impossible to mimic under laboratory conditions, and only a few groups have been cultured. We investigated the bacterial composition in the oxic-anoxic interface and in the deep waters of three sulfurous lakes from the Lake Banyoles karstic area (NE Spain) through 16S rRNA gene tag sequencing and identified the closest GenBank counterpart. High diversity indices were found in most of the samples with >15 phyla/classes and >45 bacterial orders. A higher proportion of operational taxonomic units (OTUs) of the "highest novelty" was found in the hypolimnia (38 % of total sequences) than in the metalimnia (17 %), whereas the percentage of OTUs closer to cultured counterparts (i.e., 97 % identity in the 16S rRNA gene) was 6 to 21 %, respectively. Elusimicrobia, Chloroflexi, Fibrobacteres, and Spirochaetes were the taxa with the highest proportion of novel sequences. Interestingly, tag sequencing results comparison with metagenomics data available from the same dataset, showed a systematic underestimation of sulfur-oxidizing Epsilonproteobacteria with the currently available 907R "universal" primer. Overall, despite the limitation of electron acceptors, a highly diverse and novel assemblage was present in dark and euxinic hypolimnetic freshwaters, unveiling a hotspot of microbial diversity with a remarkable gap with cultured counterparts. PMID- 26552396 TI - Persistence of Antibiotic Resistant Vibrio spp. in Shellfish Hatchery Environment. AB - The characterization of antibiotic-resistant vibrios isolated from shellfish aquaculture is necessary to elucidate the potential transfer of resistance and to establish effective strategies against vibriosis. With this aim, we analyzed a collection of bacterial isolates obtained from 15 failed hatchery larval cultures that, for the most part, had been treated experimentally with chloramphenicol to prevent vibriosis. Isolates were obtained during a 2-year study from experimental cultures of five different clam species. Among a total of 121 Vibrio isolates studied, 28 were found to be chloramphenicol resistant, suggesting that the shellfish hatchery had been using a sublethal concentration of the antibiotic. Interestingly, chloramphenicol-resistant vibrios showed also resistance to tetracycline and amoxicillin (group A; n = 19) or to streptomycin (group B; n = 9). Chloramphenicol-resistant vibrios were subjected to a PCR amplification and DNA sequencing of the chloramphenicol acetyltransferase genes (cat), and the same approach was followed to study the tetracycline resistance markers (tet). 16S ribosomal RNA (rRNA) gene sequencing revealed that chloramphenicol-resistant vibrios pertained mostly to the Splendidus clade. Conjugation assays demonstrated that various R-plasmids which harbored the cat II/tet(D) genes and cat III gene in groups A and B respectively, were transferred to E. coli and bivalve pathogenic vibrios. Most interestingly, transconjugants exhibited the antibiotic resistance patterns of the donors, despite having been selected only on the basis of chloramphenicol resistance. This is the first report carried out in a bivalve hatchery elucidating the persistence of resistant vibrios, the mechanisms of antibiotic resistance, and the transfer of different R-plasmids. PMID- 26552397 TI - Methylmercury Increases and Eicosapentaenoic Acid Decreases the Relative Amounts of Arachidonic Acid-Containing Phospholipids in Mouse Brain. AB - The membrane phospholipid composition in mammalian brain can be modified either by nutrients such as dietary fatty acids, or by certain toxic substances such as methylmercury (MeHg), leading to various biological and toxic effects. The present study evaluated the effects of eicosapentaenoic acid (EPA) and MeHg on the composition of the two most abundant membrane phospholipid classes, i.e., phosphatidylcholines (PtdCho) and phosphatidylethanolamines (PtdEtn), in mouse brain by using a two-level factorial design. The intact membrane PtdCho and PtdEtn species were analyzed by liquid chromatography-mass spectrometry. The effects of EPA and MeHg on the PtdCho and PtdEtn composition were evaluated by principal component analysis and ANOVA. The results showed that EPA and MeHg had different effects on the composition of membrane PtdCho and PtdEtn species in brain, where EPA showed strongest impact. EPA led to large reductions in the levels of arachidonic acid (ARA)-containing PtdCho and PtdEtn species in brain, while MeHg tended to elevate the levels of ARA-containing PtdCho and PtdEtn species. EPA also significantly increased the levels of PtdCho and PtdEtn species with n-3 fatty acids. Our results indicate that EPA may to some degree counteract the alterations of the PtdCho and PtdEtn pattern induced by MeHg, and thus alleviate the MeHg neurotoxicity in mouse brain through the inhibition of ARA derived pro-inflammatory factors. These results may assist in the understanding of the interaction between MeHg, EPA and phospholipids, as well as the risk and benefits of a fish diet. PMID- 26552398 TI - Linalool oxide: generalist plant based lure for mosquito disease vectors. AB - BACKGROUND: Lack of effective vaccines and therapeutics for important arboviral diseases such as Rift Valley fever (RVF) and dengue, necessitates continuous monitoring of vector populations for infections in them. Plant-based lures as surveillance tools has the potential of targeting mosquitoes of both sexes and females of varied physiological states; yet such lures are lacking for vectors of these diseases. Here, we present evidence of the effectiveness of linalool oxide (LO), a single plant-based lure previously developed for malaria vectors in trapping RVF vectors, Aedes mcintoshi and Aedes ochraceus, and dengue vector, Aedes aegypti. METHODS: For RVF vectors, we used CDC traps to evaluate the performance of LO against three vertebrate-based lures: CO2 (dry ice), BioGent (BG) lure, and HONAD (a blend of aldehydes) in 2 experiments with Completely Randomized design: 1) using unlit CDC traps baited separately with LO, HONAD and BG-lure, and unlit CDC trap + CO2 and lit CDC trap as controls, 2) similar treatments but with inclusion of CO2 to all the traps. For dengue vectors, LO was evaluated against BG lure using BG sentinel traps, in a 3 * 6 Latin Square design, first as single lures and then combined with CO2 and traps baited with CO2 included as controls. Trap captures were compared between the treatments using Chi square and GLM. RESULTS: Low captures of RVF vectors were recorded for all lures in the absence of CO2 with no significant difference between them. When combined with CO2, LO performance in trapping these vectors was comparable to BG lure and HONAD but it was less effective than the lit CDC trap. In the absence of CO2, LO performed comparably with the BG-lure in trapping female Ae. aegypti, but with significantly higher males recorded in traps baited with the plant-based lure. When CO2 was added, LO was significantly better than the BG-lure with a 2.8 fold increase in captures of male Ae. aegypti. CONCLUSIONS: These results highlight the potential of LO as a generalist plant-based lure for mosquito disease vectors, pending further assessment of possible specificity in their response profile to the different stereoisomers of this compound. PMID- 26552399 TI - Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica. AB - Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti leishmanial drug treatment strategy. Besides producing new, active anti leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising anti-leishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P < 0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach. PMID- 26552400 TI - Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix. AB - A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (<=40%) and maximum release occurred at intestinal pH values (>=90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration. PMID- 26552401 TI - In Vivo Target Validation Using Biological Molecules in Drug Development. AB - Drug development is a resource-intensive process requiring significant financial and time investment. Preclinical target validation studies and in vivo testing of the therapeutic molecules in clinically relevant disease models can accelerate and significantly de-risk later stage clinical development. In this chapter, we will focus on (1) in vivo animal models and (2) pharmacological tools for target validation. PMID- 26552402 TI - Translational In Vivo Models for Cardiovascular Diseases. AB - Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases. PMID- 26552403 TI - Emerging Target Families: Intractable Targets. AB - The druggability of a target is defined by the likelihood of a certain target binding site to be amendable to functional modulation by a small molecule in vivo. Thus, druggability depends on the ability of the developed small molecule to reach the target site, the properties of the ligand binding pocket and our ability to develop chemical matter that efficiently interact with the drug binding site of interest. Historically enzymes have been the main drug targets because the inhibition of their activity can be easily assayed and catalytic centres are often attractive drug binding sites. However, despite considerable effort, a number of classical enzyme families have not been successfully targeted. More recently protein-protein interactions received considerable attention and several clinical inhibitors have now been developed. Despite the considerable progress made expanding target space, a large number of targets with a very strong rationale for targeting remain intractable. In the following chapter I will summarize progress made in developing inhibitors for challenging drug binding sites and emerging target families. PMID- 26552404 TI - Protective Effects of Growth Arrest-Specific Protein 6 (Gas6) on Sepsis-Induced Acute Kidney Injury. AB - Acute kidney injury (AKI) is a serious complication of sepsis, which has a high mortality rate. Growth arrest-specific protein 6 (Gas6), the protein product of the growth arrest specific gene 6, has been shown to have an anti-apoptotic effect as well as pro-survival capability. Here, we investigated the effects of Gas6 on sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP). We found that the administration of rmGas6 significantly reduced serum urea nitrogen and creatinine and improved the survival of septic mice. Furthermore, the renal pathological damage induced by CLP was attenuated by rmGas6 treatment. Finally, rmGas6 reduced the renal tissue apoptotic index and the expression of Bax, while it upregulated the expression of Bcl-2. The data suggest that rmGas6 might be used as a potential therapeutic agent for sepsis induced AKI. PMID- 26552405 TI - Licochalcone A Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting NF-kappaB Activation. AB - Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. However, the protective effects of Lico A on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) remains unclear. In this study, using a mouse model of LPS-induced AKI, we investigated the protective effects and mechanism of Lico A on LPS-induced AKI in mice. LPS-induced kidney injury was assessed by detecting kidney histological study, blood urea nitrogen (BUN), and creatinine levels. The production of inflammatory cytokines TNF-alpha, IL-6, and IL-1beta in serum and kidney tissues was detected by ELISA. The activation of NF-kappaB was measured by western blot analysis. Our results showed that Lico A dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. Lico A also suppressed LPS-induced TNF-alpha, IL-6, and IL-1beta production both in serum and kidney tissues. Furthermore, our results showed that Lico A significantly inhibited LPS-induced NF-kappaB activation. In conclusion, our results suggest that Lico A has protective effects against LPS-induced AKI and Lico A exhibits its anti-inflammatory effects through inhibiting LPS-induced NF-kappaB activation. PMID- 26552406 TI - The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment. PMID- 26552407 TI - A curious case of acute respiratory distress syndrome. AB - Gestational acute respiratory distress syndrome (ARDS) is a complicated problem with the potential to gravely harm both mother and fetus. This case report describes a young woman in her second trimester of pregnancy who developed progressive respiratory failure in the setting of newly diagnosed influenza, diffuse alveolar hemorrhage and lymphangioleiomyomatosis. The patient's condition was refractory to conventional interventions and required extracorporeal membrane oxygenation (ECMO) support. Her course was further complicated by preeclampsia requiring preterm delivery with cesarean section while on ECMO. Through novel therapies and a multidisciplinary approach to care, both the patient and her child would overcome these unique and challenging conditions and survive. PMID- 26552409 TI - Resource needs and gap analysis in achieving universal access to HIV/AIDS services: a data envelopment analysis of 45 countries. AB - BACKGROUND: -To manage the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) epidemic, international donors have pledged unprecedented commitments for needed services. The Joint United Nations Programme on HIV/AIDS (UNAIDS) projected that low- and middle-income countries needed $25 billion to meet the 2010 HIV/AIDS goal of universal access to AIDS prevention and care, using the resource needs model (RNM). METHODS: -Drawing from the results from its sister study, which used a data envelopment analysis (DEA) and a Tobit model to evaluate and adjust the technical efficiency of 61 countries in delivering HIV/AIDS services from 2002 to 2007, this study extended the DEA and developed an approach to estimate resource needs and decompose the performance gap into efficiency gap and resource gap. In the DEA, we considered national HIV/AIDS spending as the input and volume of voluntary counseling and testing (VCT), prevention of mother to child transmission (PMTCT) and antiretroviral treatment (ART) as the outputs. An input-oriented DEA model was constructed to project resource needs in achieving 2010 HIV/AIDS goal for 45 countries using the data in 2006, assuming that all study countries maximized efficiency. FINDINGS: The DEA approach demonstrated the potential to include efficiency of national HIV/AIDS programmes in resource needs estimation, using macro-level data. Under maximal efficiency, the annual projected resource needs for the 45 countries was $6.3 billion, ~47% of their UNAIDS estimate of $13.5 billion. Given study countries' spending of $3.9 billion, improving efficiency could narrow the gap from $9.6 to $2.4 billion. The results suggest that along with continued financial commitment to HIV/AIDS, improving the efficiency of HIV/AIDS programmes would accelerate the pace to reach 2010 HIV/AIDS goals. The DEA approach provides a supplement to the AIDS RNM to inform policy making. PMID- 26552408 TI - Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model. AB - Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (Thrb(PV/PV)Pten(+/-) mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD induced aggressive cancer progression in the mouse model of thyroid cancer. WT and Thrb(PV/PV)Pten(+/-) mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated Thrb(PV/PV)Pten(+/-) mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated Thrb(PV/PV)Pten(+/-) mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer. PMID- 26552410 TI - Altruistic Preferences in Time Tradeoff: Consideration of Effects on Others in Health State Valuations. AB - Whether respondents incorporate altruistic preferences in time tradeoff (TTO) exercises remains understudied. We present an extended quality-adjusted life-year model incorporating altruism. We derive that altruism may affect TTO values in 2 directions. First, "longevity altruists" may wish to prolong life for the sake of their loved ones (to avoid being missed). Second, "quality-of-life altruists" may have a preference to avoid bad health states resulting in being a burden to loved ones. The existence and influence of these preferences in a TTO were empirically confirmed in a sample of 1690 respondents from the general public. We classified respondents as "longevity altruists" or "quality-of-life altruists" based on their reasoning behind inclusion of loved ones in their TTO responses. In line with expectations, longevity altruists traded fewer years than quality-of-life altruists. Nonaltruists gave intermediate values. PMID- 26552411 TI - Disseminated eruptive free sebaceous glands on the face as a rare sequela of toxic epidermal necrolysis. PMID- 26552412 TI - Factors associated with occupational injuries in seasonal young workers. AB - BACKGROUND: Younger workers are more likely to be injured on the job than older workers. Investigation tends to focus on work-related explanatory factors but often neglects non-work-related causes. AIMS: To identify both work- and non-work related factors that contribute to younger workers' injuries in seasonal work. METHODS: Two surveys of a set of seasonal parks and recreation workers were conducted measuring health and safety behaviours and self-reported injuries. RESULTS: Seventy per cent reported an injury at work over the summer. Among young workers, each additional year of age was associated with an almost 50% increase in injury rate (P < 0.05). Odds of injury in women were three times those for men (P < 0.05). We observed a linear relationship between average hours worked per week and injuries (P < 0.001). Alcohol abuse (P < 0.05) was also associated with injuries. CONCLUSIONS: Higher injury rates among younger workers in this sample is multifactorial and encompasses both work and non-work factors and suggest that more global approaches are required to address young worker safety. PMID- 26552414 TI - First Oncolytic Viral Therapy for Melanoma. AB - The FDA has approved talimogene laherparepvec, or T-VEC, to treat surgically unresectable skin and lymph node lesions in patients with advanced melanoma. T VEC is the first oncolytic viral therapy to gain regulatory endorsement, based on data from the OPTiM study. PMID- 26552415 TI - Time loss injuries compromise team success in Elite Rugby Union: a 7-year prospective study. AB - BACKGROUND: A negative association between injuries and team success has been demonstrated in professional football, but the nature of this association in elite Rugby Union teams is currently unclear. AIM: To assess the association between injury burden measures and team success outcomes within professional Rugby Union teams. METHODS: A seven-season prospective cohort design was used to record all time-loss injuries incurred by English Premiership players. Associations between team success measures (league points tally and Eurorugby Club Ranking (ECR)) and injury measures (injury burden and injury days per team match) were modelled, both within (changes from season to season) and between (differences averaged over all seasons) teams. Thresholds for the smallest worthwhile change in league points tally and ECR were 3 points and 2.6%, respectively. RESULTS: Data from a total of 1462 players within 15 Premiership teams were included in the analysis. We found clear negative associations between injury measures and team success (70-100% likelihood), with the exception of between-team differences for injury days per team-match and ECR, which was unclear. A reduction in injury burden of 42 days (90% CI 30 to 70) per 1000 player hours (22% of mean injury burden) was associated with the smallest worthwhile change in league points tally. CONCLUSIONS: Clear negative associations were found between injury measures and team success, and moderate reductions in injury burden may have worthwhile effects on competition outcomes for professional Rugby Union teams. These findings may be useful when communicating the value of injury prevention initiatives within this elite sport setting. PMID- 26552413 TI - Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer. AB - Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, and are important contributors to malignancy and potential biomarkers and targets for immunotherapy. SIGNIFICANCE: The tumor microenvironment and tumor-associated inflammation are now appreciated not only for their role in cancer progression but also for their response to therapy. The lymphatic vasculature is a less appreciated component of this microenvironment that coordinates local inflammation and immunity and thereby critically shapes local responses. A mechanistic understanding of the complexities of lymphatic vessel function in the unique context of skin provides a model to understand how regional immune dysfunction drives cutaneous malignancies, and as such lymphatic vessels represent a biomarker of cutaneous immunity that may provide insight into cancer prognosis and effective therapy. PMID- 26552416 TI - Dose-response association of screen time-based sedentary behaviour in children and adolescents and depression: a meta-analysis of observational studies. AB - BACKGROUND: Depression represents a growing public health burden. Understanding how screen time (ST) in juveniles may be associated with risk of depression is critical for the development of prevention and intervention strategies. Findings from studies addressing this question thus far have been inconsistent. Therefore, we conducted a comprehensive systematic review and meta-analysis of data related to this question. METHODS: The meta-analysis was conducted in accordance with the PRISMA guideline. We searched the electronic databases of PubMed, Web of Science and EBSCO systematically (up to 6 May 2015). OR was adopted as the pooled measurement of association between ST and depression risk. Dose-response was estimated by a generalised least squares trend estimation. RESULTS: Twelve cross sectional studies and four longitudinal studies (including 1 cohort study) involving a total of 127 714 participants were included. Overall, higher ST in preadolescent children and adolescents was significantly associated with a higher risk of depression (OR=1.12; 95% CI 1.03 to 1.22). Screen type, age, population and reference category acted as significant moderators. Compared with the reference group who had no ST, there was a non-linear dose-response association of ST with a decreasing risk of depression at ST<2 h/day, with the lowest risk being observed for 1 h/day (OR=0.88; 95% CI 0.84 to 0.93). CONCLUSIONS: Our meta analysis suggests that ST in children and adolescents is associated with depression risk in a non-linear dose-response manner. PMID- 26552418 TI - Epilepsy and Adult Neurogenesis. AB - Seizure activity in the hippocampal region strongly affects stem cell-associated plasticity in the adult dentate gyrus. Here, we describe how seizures in rodent models of mesial temporal lobe epilepsy (mTLE) affect multiple steps in the developmental course from the dividing neural stem cell to the migrating and integrating newborn neuron. Furthermore, we discuss recent evidence indicating either that seizure-induced aberrant neurogenesis may contribute to the epileptic disease process or that altered neurogenesis after seizures may represent an attempt of the injured brain to repair itself. Last, we describe how dysfunction of adult neurogenesis caused by chronic seizures may play an important role in the cognitive comorbidities associated with mTLE. PMID- 26552417 TI - The Origins and Organization of Vertebrate Pavlovian Conditioning. AB - Pavlovian conditioning is the process by which we learn relationships between stimuli and thus constitutes a basic building block for how the brain constructs representations of the world. We first review the major concepts of Pavlovian conditioning and point out many of the pervasive misunderstandings about just what conditioning is. This brings us to a modern redefinition of conditioning as the process whereby experience with a conditional relationship between stimuli bestows these stimuli with the ability to promote adaptive behavior patterns that did not occur before the experience. Working from this framework, we provide an in-depth analysis of two examples, fear conditioning and food-based appetitive conditioning, which include a description of the only partially overlapping neural circuitry of each. We also describe how these circuits promote the basic characteristics that define Pavlovian conditioning, such as error-correction driven regulation of learning. PMID- 26552420 TI - Lavage of the Uterine Cavity for Molecular Detection of Mullerian Duct Carcinomas: A Proof-of-Concept Study. AB - PURPOSE: Type II ovarian cancer (OC) and endometrial cancer (EC) are generally diagnosed at an advanced stage, translating into a poor survival rate. There is increasing evidence that Mullerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells. PATIENTS AND METHODS: Lavage of the uterine cavity was used to obtain samples from 65 patients, including 30 with OC, five with EC, three with other malignancies, and 27 with benign lesions involving gynecologic organs. These samples, as well as corresponding tumor tissue, were examined for the presence of somatic mutations using massively parallel sequencing (next-generation sequencing) and, in a subset, singleplex analysis. RESULTS: The lavage technique could be applied successfully, and sufficient amounts of DNA were obtained in all patients. Mutations, mainly in TP53, were identified in 18 (60%) of 30 lavage samples of patients with OC using next-generation sequencing. Singleplex analysis of mutations previously determined in corresponding tumor tissue led to further identification of six patients. Taken together, in 24 (80%) of 30 patients with OC, specific mutations could be identified. This also included one patient with occult OC. All five analyzed lavage specimens from patients with EC harbored mutations. Eight (29.6%) of 27 patients with benign lesions tested positive for mutations, six (75%) as a result of mutations in the KRAS gene. CONCLUSION: This study proved that tumor cells from ovarian neoplasms are shed and can be collected via lavage of the uterine cavity. Detection of OC and EC and even clinically occult OC was achieved, making it a potential tool of significant promise for early diagnosis. PMID- 26552419 TI - Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. AB - PURPOSE: The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. PATIENTS AND METHODS: ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. RESULTS: Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. CONCLUSION: Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease. PMID- 26552421 TI - Evaluating Intermittent Androgen-Deprivation Therapy Phase III Clinical Trials: The Devil Is in the Details. AB - PURPOSE: Intermittent androgen deprivation (IAD) has been widely tested in prostate cancer. However, phase III trials testing continuous androgen deprivation (CAD) versus IAD have reached inconclusive and seemingly contradictory results. Different design and conduct issues must be critically evaluated to better interpret the results. PATIENTS AND METHODS: Seven published phase III trials were examined for prespecified design and outcomes. Treatment specifications; primary end point; superiority versus noninferiority design assumptions, including magnitude of assumed versus observed noninferiority margin (NIM); duration of follow-up; and quality-of-life (QOL) outcomes were considered in terms of the results and conclusions reported. RESULTS: Five trials had a superiority and three had a noninferiority primary hypothesis. Only three trials had a uniform population and overall survival (OS) end point. All trials observed better outcomes in terms of OS and progression-free survival (PFS) than assumed at time of study design, translating into prespecified NIMs or hazard ratios that reflected larger absolute differences in OS or PFS between arms. Lower-than expected event rates also reduced statistical power for the trials. Other factors, including length of follow-up, cause of death, QOL, and primary end point, and their impact on trial interpretation are discussed. CONCLUSION: No trial to date has demonstrated survival superiority of IAD compared with CAD. Trials concluding IAD is noninferior to CAD were based on wide NIMs that included clinically important survival differences, not likely to be considered comparable by physicians or patients. Interim analyses relying on short follow-up and including a majority of non-prostate cancer deaths will favor a noninferiority conclusion and should be interpreted cautiously. Adequate follow-up is required to ensure capture of prostate cancer deaths in both superiority and noninferiority trials. PMID- 26552422 TI - Novel affinity binders for neutralization of vascular endothelial growth factor (VEGF) signaling. AB - Angiogenesis denotes the formation of new blood vessels from pre-existing vasculature. Progression of diseases such as cancer and several ophthalmological disorders may be promoted by excess angiogenesis. Novel therapeutics to inhibit angiogenesis and diagnostic tools for monitoring angiogenesis during therapy, hold great potential for improving treatment of such diseases. We have previously generated so-called biparatopic Affibody constructs with high affinity for the vascular endothelial growth factor receptor-2 (VEGFR2), which recognize two non overlapping epitopes in the ligand-binding site on the receptor. Affibody molecules have previously been demonstrated suitable for imaging purposes. Their small size also makes them attractive for applications where an alternative route of administration is beneficial, such as topical delivery using eye drops. In this study, we show that decreasing linker length between the two Affibody domains resulted in even slower dissociation from the receptor. The new variants of the biparatopic Affibody bound to VEGFR2-expressing cells, blocked VEGFA binding, and inhibited VEGFA-induced signaling of VEGFR2 over expressing cells. Moreover, the biparatopic Affibody inhibited sprout formation of endothelial cells in an in vitro angiogenesis assay with similar potency as the bivalent monoclonal antibody ramucirumab. This study demonstrates that the biparatopic Affibody constructs show promise for future therapeutic as well as in vivo imaging applications. PMID- 26552423 TI - Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention. AB - OBJECTIVES: Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). METHODS: Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. RESULTS: The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6+/-13.2 years vs. 46.6+/-10.9 years), and disease duration (15.3+/-6.7 months vs. 14.5+/-6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. CONCLUSIONS: Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities. PMID- 26552424 TI - Modifiable risk factors of lung cancer in "never-smoker" women. AB - Korean women with a history of never smoking and with adenocarcinoma showed an increasing trend in lung cancer occurrence during 2002 to 2012. The two modifiable factors of never-smoker lung cancer in women are hormone and oncogenic virus infection. Based on previous studies, hormone replacement therapy (HRT) and human papillomavirus (HPV) infection might afford protection or be a risk factor, respectively. It is necessary to perform a pooled analysis of cohort studies to evaluate HRT and never-smoker lung cancer in women and a systematic review of case-control studies to determine the association between HPV infection and never smoker lung cancer. PMID- 26552425 TI - Feasibility of "CopeSmart": A Telemental Health App for Adolescents. AB - BACKGROUND: Early intervention is important in order to improve mental health outcomes for young people. Given the recent rise in mobile phone ownership among adolescents, an innovative means of delivering such intervention is through the use of mobile phone applications (apps). OBJECTIVE: The aim of this study was to evaluate the feasibility of "CopeSmart", a telemental health app developed to foster positive mental health in adolescents through emotional self-monitoring and the promotion of positive coping strategies. METHODS: Forty-three adolescents (88% female) aged 15-17 years downloaded the app and used it over a one-week period. They then completed self-report questionnaires containing both open-ended and closed-ended questions about their experiences of using the app. The app itself captured data related to user engagement. RESULTS: On average participants engaged with the app on 4 of the 7 days within the intervention period. Feedback from users was reasonably positive, with 70% of participants reporting that they would use the app again and 70% reporting that they would recommend it to a friend. Thematic analysis of qualitative data identified themes pertaining to users' experiences of the app, which were both positive (eg, easy to use, attractive layout, emotional self-monitoring, helpful information, notifications, unique) and negative (eg, content issues, did not make user feel better, mood rating issues, password entry, interface issues, engagement issues, technical fixes). CONCLUSIONS: Overall findings suggest that telemental health apps have potential as a feasible medium for promoting positive mental health, with the majority of young people identifying such technologies as at least somewhat useful and displaying a moderate level of engagement with them. Future research should aim to evaluate the efficacy of such technologies as tools for improving mental health outcomes in young people. PMID- 26552426 TI - The Tree Theme Method(r) (TTM), an occupational therapy intervention for treating depression and anxiety: study protocol of a randomized controlled trial. AB - BACKGROUND: Depression and anxiety disorders are increasing among the general population in the Western world. Individuals may need several kinds of treatment in order to maintain health, such as cognitive behavioural therapy (CBT) and drug treatment. However, having an everyday life that "works" is also important, suggesting a need for interventions based on activities that facilitate a satisfying everyday life. There is still lack of such evidence-based interventions. The Tree Theme Method((r)) (TTM) is an occupational therapy intervention designed for a client-centred context in which an individual develops strategies to become an actor in his or her everyday life. Previous studies of the TTM have focused on process evaluation; therefore, further studies are needed to evaluate the method's effects. The aim of this paper is to outline an intervention that can evaluate the effects of the TTM in terms of psychological symptoms, as well as everyday occupations and well-being, in patients suffering from depression and anxiety. METHODS/DESIGN: This randomized clinical trial includes patients from three Swedish counties randomized to either intervention or treatment as usual. Men and women aged 18-65 years who have been diagnosed with either depression or anxiety are eligible for inclusion. Data collection is carried out at baseline, and outcomes are assessed at the end of intervention, as well as at 3 months and 12 months after intervention ends. The outcomes measured are psychological symptoms, everyday activities, and health related factors. DISCUSSION: Depression and anxiety may create difficulties for individuals in the activities of their everyday lives to the extent that they require diagnosis and intervention. Despite this reality, evidence-based interventions that focus on everyday activities are lacking. Therefore, it would be useful to design a specific method for occupational therapy intervention that does precisely that. This study provides insight into the effects of the TTM, comparing it to occupational therapy treatment as usual. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01980381; registered November 2013. PMID- 26552427 TI - Obstetric and psychosocial risk factors for Australian-born and non-Australian born women and associated pregnancy and birth outcomes: a population based cohort study. AB - BACKGROUND: One in four Australians is born overseas and 47% are either born overseas or have a parent who was. Obstetric and psychosocial risk factors for these women may differ. METHOD: Data from one Sydney hospital (2012-2013) of all births recorded in the ObstetriX database were analysed (n = 3,092). Demographics, obstetric and psychosocial risk profile, obstetric interventions and complications and selected maternal and neonatal outcomes were examined for women born in Australia and overseas. RESULTS: Women born in Australia were younger, more likely to be primiparous (28.6 v 27.5%), be obese (32.0% v 21.4%), smoke (19.7 % v 3.0%), have an epidural (26.2% v 20.2%) and were less likely to have gestational diabetes mellitus (GDM) (6.8% v 13.7% when compared to non Australian born women. The highest rates of GDM, Gestational Hypertension (GH) and maternal anaemia were seen in women born in China, the Philippines and Pakistan respectively. Differences were also seen in psychosocial screening between Australian and non-Australian women with Australian-born women more likely to smoke and report a mental health disorder. There was an association between having an Edinburgh Postnatal Depression Scale (EPDS) >= 13 and other psychosocial issues, such as thoughts of self-harm, domestic violence, childhood abuse etc. These women were also less likely to breastfeed. Women with an EPDS >= 13 at booking compared to women with EPDS <=12 had a higher chance of being diagnosed with GDM (AOR 1.85 95% CI 1.14-3.0). CONCLUSIONS: There are significant differences in obstetric and psychosocial risk profiles and maternal and neonatal outcomes between Australian-born and non-Australian born women. In particular there appears to be an association between an EPDS of >=13 and developing GDM, which warrants further investigation. PMID- 26552428 TI - Transmission-blocking activity of antibodies to Plasmodium falciparum GLURP.10C chimeric protein formulated in different adjuvants. AB - BACKGROUND: Plasmodium falciparum is transmitted from person to person by Anopheles mosquitoes after completing its sexual reproductive cycle within the infected mosquito. An efficacious vaccine holds the potential to interrupt development of the parasite in the mosquito leading to control and possibly eradication of malaria. A multi-component, R0.10C, was developed comprising P. falciparum glutamate-rich protein (R0) fused in frame to a correctly folded fragment of Pfs48/45 (10C). Here, a series of novel adjuvants were screened for their ability to elicit transmission-blocking (TB) antibodies. METHODS: The recombinant fusion protein R0.10C was produced in Lactococcus lactis and purified by affinity-chromatography on a monoclonal antibody (mAb 85RF45.1) against a major epitope for TB antibodies (epitope 1) harboured on R0.10C. Immune-purified R0.10C was mixed with a series of adjuvants and tested in mice and rats. RESULTS: In general, all R0.10C formulations elicited high levels of antibodies recognizing native Pfs48/45 in macrogametes/zygotes. TB activity of anti-R0.10C antisera was assessed in the standard membrane-feeding assay (SMFA). Potency of different adjuvant/R0.10C combinations was tested in mice and rats using aluminium hydroxide (Alum), Alum with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA), stable emulsion (SE)/GLA, AbISCO-100 and Freund's adjuvant (as reference). All formulations produced high antibody titres recognizing the native Pfs48/45 protein in macrogametes/zygotes. Interestingly, the GLA-Alum combination adjuvant was the most potent inducer of TB antibodies based on serum collected after two immunizations. In agreement with previous observations, biological activity in the SMFA correlated well with the level of anti-Pfs48/45 antibodies. CONCLUSION: The combined data provide a strong basis for entering the next phase of clinical grade R0.10C production and testing. PMID- 26552429 TI - Variant mapping and mutation discovery in inbred mice using next-generation sequencing. AB - BACKGROUND: The development of powerful new methods for DNA sequencing enable the discovery of sequence variants, their utilization for the mapping of mutant loci, and the identification of causal variants in a single step. We have applied this approach for the analysis of ENU-mutagenized mice maintained on an inbred background. RESULTS: We ascertained ENU-induced variants in four different phenotypically mutant lines. These were then used as informative markers for positional cloning of the mutated genes. We tested both whole genome (WGS) and whole exome (WES) datasets. CONCLUSION: Both approaches were successful as a means to localize a region of homozygosity, as well as identifying mutations of candidate genes, which could be individually assessed. As expected, the WGS strategy was more reliable, since many more ENU-induced variants were ascertained. PMID- 26552430 TI - Associations between workplace affiliation and phlebotomy practices regarding patient identification and test request handling practices in primary healthcare centres: a multilevel model approach. AB - BACKGROUND: Clinical practice guidelines aim to enhance patient safety by reducing inappropriate variations in practice. Despite considerable efforts to enhance the use of clinical practice guidelines, adherence is often suboptimal. We investigated to what extent workplace affiliation explains variation of self reported adherence to venous blood specimen collection regarding patient identification and test request handling practices, taking into consideration other primary healthcare centre and individual phlebotomist characteristics. METHODS: Data were collected through a questionnaire survey of 164 phlebotomy staff from 25 primary healthcare centres in northern Sweden. To prevent the impact of a large-scale education intervention in 2008, only baseline data, collected over a 3-month period in 2006-2007, were used and subjected to descriptive statistics and multilevel logistic analyses. RESULTS: In two patient identification outcomes, stable high median odds ratios (MOR) were found in both the empty model, and in the adjusted full model including both individual and workplace factors. Our findings suggest that variances among phlebotomy staff can be largely explained by primary healthcare centre affiliation also when individual and workplace demographic characteristics were taken in consideration. Analyses showed phlebotomy staff at medium and large primary healthcare centres to be more likely to adhere to guidelines than staff at small centres. Furthermore, staff employed shorter time at worksite to be more likely to adhere than staff employed longer. Finally, staff performing phlebotomy every week or less were more likely to adhere than staff performing phlebotomy on a daily basis. CONCLUSION: Workplace affiliation largely explains variances in self reported adherence to venous blood specimen collection guidelines for patient identification and test request handling practices among phlebotomy staff. Characteristics of the workplace, as well as of the individual phlebotomist, need to be identified in order to design strategies to improve clinical practice in this and other areas. PMID- 26552431 TI - Alcohol consumption, body mass index and breast cancer risk by hormone receptor status: Women' Lifestyle and Health Study. AB - BACKGROUND: We aimed to estimate the effect of alcohol consumption on breast cancer risk and to test whether overweight and obesity modifies this association. METHODS: We included in the analysis 45,233 women enrolled in the Swedish Women's Lifestyle and Health study between 1991 and 1992. Participants were followed for occurrence of breast cancer and death until December 2009. Poisson regression models were used, and analyses were done for overall breast cancer and for estrogen receptor positive or negative (ER+, ER-) and progesterone receptor positive and negative (PR+, PR-) tumors separately. RESULTS: A total of 1,385 breast cancer cases were ascertained during the follow-up period. Overall, we found no statistically significant association between alcohol intake and breast cancer risk after adjustment for confounding, with an estimated relative risk (RR) of 1.01 (95 % CI: 0.98-1.04) for an increment in alcohol consumption of 5 g/day. A statistically significant elevated breast cancer risk associated with higher alcohol consumption was found only among women with BMI <=25 (RR 1.03, 95 % CI 1.0-1.05 per 5 g/day increase). CONCLUSION: An increase in breast cancer risk with higher alcohol consumption was found for breast cancers in women with a BMI <=25 kg/m(2). PMID- 26552432 TI - Benefits of an expanded use of plasma exchange for anti-neutrophil cytoplasmic antibody-associated vasculitis within a dedicated clinical service. AB - BACKGROUND: Current recommendations for ANCA-associated vasculitis (AAV) support its management within a dedicated clinical service. Therapies for AAV are imperfect with many patients failing to achieve disease control and others experiencing disease relapse. Plasma exchange (PEX) may be beneficial especially when the kidney is involved. METHODS: Within a new, dedicated service we retrospectively assessed, over a 6-year period, the benefits of PEX in two patient cohorts, discriminated by PEX treatment alone. Patients received PEX alongside standard of care if they fulfilled any of the following criteria: 1. serum creatinine >500 MUmol/l or dialysis-requiring renal failure, 2. alveolar haemorrhage, 3. renal biopsy showing >=30 % focal and necrotising lesions +/- cellular crescents. Outcome measures included disease remission and relapse, cumulative immunosuppression, and morbidity and mortality. RESULTS: Of 104 new patients, 58 patients received PEX at presentation, 46 did not. Cyclophosphamide and/or rituximab dosing was similar for both groups. Although patients receiving PEX had poorer renal function, a higher C-reactive protein and disease activity score at presentation disease remission rate was similar in both groups (no PEX vs. PEX: 96 % vs. 98 %). The PEX group entered remission quicker (no PEX vs. PEX: 3.9 +/- 4.0 vs. 2.8 +/- 1.3 months, p < 0.05), with a lower 3-month cumulative glucocorticoid dose (no PEX vs. PEX: 2.5 +/- 0.4 vs. 2.3 +/- 0.2 g, p < 0.001). Relapse was similar between groups but adverse events lower in the PEX group. CONCLUSIONS: PEX may be of benefit in AAV. Larger, longer randomised controlled trials are now needed. PMID- 26552433 TI - High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review. AB - Nowadays, enzymes can be efficiently identified and screened from metagenomic resources or mutant libraries. A set of a few hundred new enzymes can be found using a simple substrate within few months. Hence, the establishment of collections of enzymes is no longer a big hurdle. However, a key problem is the relatively low rate of positive hits and that a timeline of several years from the identification of a gene to the development of a process is the reality rather than the exception. Major problems are related to the time-consuming and cost-intensive screening process that only very few enzymes finally pass. Accessing to the highest possible enzyme and mutant diversity by different, but complementary approaches is increasingly important. The aim of this review is to deliver state-of-art status of traditional and novel screening protocols for targeting lipases, esterases and phospholipases of industrial relevance, and that can be applied at high throughput scale (HTS) for at least 200 distinct substrates, at a speed of more than 105 - 108 clones/day. We also review fine tuning sequence analysis pipelines and in silico tools, which can further improve enzyme selection by an unprecedent speed (up to 1030 enzymes). If the hit rate in an enzyme collection could be increased by HTS approaches, it can be expected that also the very further expensive and time-consuming enzyme optimization phase could be significantly shortened, as the processes of enzyme-candidate selection by such methods can be adapted to conditions most likely similar to the ones needed at industrial scale. PMID- 26552434 TI - From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review. AB - Feruloyl esterases (FAEs) are a diverse group of hydrolases widely distributed in plants and microorganisms which catalyzes the cleavage and formation of ester bonds between plant cell wall polysaccharides and phenolic acids. FAEs have gained importance in biofuel, medicine and food industries due to their capability of acting on a large range of substrates for cleaving ester bonds and synthesizing highadded value molecules through esterification and transesterification reactions. During the past two decades extensive studies have been carried out on the production, characterization and classification of FAEs, however only a few reports of suitable High Throughput Screening assays for this kind of enzymes have been reported. This review is focused on a concise but complete revision of classical to High Throughput Screening methods for FAEs, highlighting its advantages and disadvantages, and finally suggesting future perspectives for this important research field. PMID- 26552435 TI - Proteases and their Inhibitors: From Basic to High Throughput Screening. AB - Proteases constitute one of the most important groups of industrial enzymes with a worldwide value expected to reach 2.7 billion US dollars by 2019. Proteases represent a group of enzymes that hydrolyze the peptide bonds of proteins, releasing polypeptides or free amino acids. These enzymes are used in cleaning products, production of leathers, textiles, food and dairy products, in the pharmaceutical and diagnostic industries and for water treatment. Another area of interest regarding proteases is the development of drugs that act as protease inhibitors. This review will briefly describe the general methods used in the detection of proteases and the few studies in the development of high throughput screening methods of proteases and protease inhibitors. PMID- 26552436 TI - Prediction of bioactive compound pathways using chemical interaction and structural information. AB - The functional screening of compounds is an important topic in chemistry and biomedicine that can uncover the essential properties of compounds and provide information concerning their correct use. In this study, we investigated the bioactive compounds reported in Selleckchem, which were assigned to 22 pathways. A computational method was proposed to identify the pathways of the bioactive compounds. Unlike most existing methods that only consider compound structural information, the proposed method adopted both the structural and interaction information from the compounds. The total accuracy achieved by our method was 61.79% based on jackknife analysis of a dataset of 1,832 bioactive compounds. Its performance was quite good compared with that of other machine learning algorithms (with total accuracies less than 46%). Finally, some of the false positives obtained by the method were analyzed to investigate the likelihood of compounds being annotated to new pathways. PMID- 26552437 TI - Analysis of the relationship between PM2.5 and lung cancer based on protein protein interactions. AB - Lung cancer, characterized by uncontrolled cell growth in tissues of the lung, is one of the leading causes of cancer mortality worldwide. Many etiologic factors for lung cancer tumorigenesis have been identified to date, such as smoking and exposure to radon, cooking fumes and asbestos. Atmospheric pollution has become increasingly heavy in China in recent years. Accordingly, greater numbers of people are paying attention to the air quality around them. PM2.5 (particulate matter with a diameter of 2.5 micrometers or less), which is one of the most important indicators for measuring air quality, can penetrate and be retained in lung tissue. It is believed that PM2.5 may represent a new type of etiological factor for lung cancer. This study constitutes the analysis of the association between PM2.5 and lung cancer. Genes related to small/nonsmall cell lung cancer were evaluated by assigning scores to measure the impact caused by PM2.5. Analyses of small/nonsmall cell lung cancer genes with high scores revealed that it is theoretically possible that PM2.5 is an etiologic factor for lung cancer. Our results provided new insights of the relationship between lung cancers and air pollution. PMID- 26552438 TI - Large-Scale Prediction of Drug Targets Based on Local and Global Consistency of Chemical-Chemical Networks. AB - It is crucial to identify the molecular targets of a compound during the course of the new drug discovery and drug development. Due to the complexity of biological systems, finding drug targets by biological experiments is very tedious and expensive. In the paper, we used chemicalchemical interactions in the STITCH database to construct a network of drug-drug association. Based on the network, a learning method keeping local and global consistency was presented to infer drug targets. We achieved an accuracy of 57.75% in the first order prediction using leave-one-out cross validation, which was higher than the accuracy of 53.77% achieved by the local neighbor model. We manually validated 27 absent drug targets in the crossvalidation using drug-target interactions from other databases. Applying the presented method to large-scale prediction of unknown targets, we manually confirmed 14 pairs of drug-target interactions among the newly predicted drug targets. These results suggested that the presented method was a promising tool for large-scale identification of drug targets. PMID- 26552439 TI - Study of drug-drug combinations based on molecular descriptors and physicochemical properties. AB - In the present study, molecular descriptors and physicochemical properties were used to encode drug molecules. Based on this molecular representation method, Random forest was applied to construct a drug-drug combination network. After feature selection, an optimal features subset was built, which described the main factors of drugs in our prediction. As a result, the selected features can be clustered into three categories: elemental analysis, chemistry, and geometric features. And all of the three types features are essential elements of the drug drug combination network. The final prediction model achieved a Matthew's correlation coefficient (MCC) of 0.5335 and an overall prediction accuracy of 88.79% for the 10-fold cross-validation test. PMID- 26552440 TI - A novel machine learning method for cytokine-receptor interaction prediction. AB - Most essential functions are associated with various protein-protein interactions, particularly the cytokine-receptor interaction. Knowledge of the heterogeneous network of cytokine- receptor interactions provides insights into various human physiological functions. However, only a few studies are focused on the computational prediction of these interactions. In this study, we propose a novel machine-learning-based method for predicting cytokine-receptor interactions. A protein sequence is first transformed by incorporating the sequence evolutional information and then formulated with the following three aspects: (1) the k-skip-n-gram model, (2) physicochemical properties, and (3) local pseudo position-specific score matrix (local PsePSSM). The random forest classifier is subsequently employed to predict potential cytokine-receptor interactions. Experimental results on a dataset of Homo sapiens show that the proposed method exhibits improved performance, with 3.4% higher overall prediction accuracy, than existing methods. PMID- 26552441 TI - Predicting the types of metabolic pathway of compounds using molecular fragments and sequential minimal optimization. AB - A metabolic pathway is a series of biological processes providing necessary molecules and energies for an organism, which could be essential to the lives of the living organisms. Most metabolic pathways require the involvement of compounds and given a compound it is helpful to know what types of metabolic pathways the compound participates in. In this study, compounds are first represented by molecular fragments which are then delivered to a prediction engine called Sequential Minimal Optimization (SMO) for predictions. Maximum relevance and minimum redundancy (mRMR) and incremental feature selection are adopted to extract key features based on which an optimal prediction engine is established. The proposed method is effective comparing to the random forest, Dagging and a popular method that integrating chemical-chemical interactions and chemical-chemical similarities. We also make predictions using some compounds with unknown metabolic pathways and choose 17 compounds for analysis. The results indicate that the method proposed may become a useful tool in predicting and analyzing metabolic pathways. PMID- 26552442 TI - Analysis of A Drug Target-based Classification System using Molecular Descriptors. AB - Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes. PMID- 26552443 TI - Are Topological Properties of Drug Targets Based on Protein-Protein Interaction Network Ready to Predict Potential Drug Targets? AB - Identification of potential druggable targets utilizing protein-protein interactions network (PPIN) has been emerging as a hotspot in drug discovery and development research. However, it remains unclear whether the currently used PPIN topological properties are enough to discriminate the drug targets from non-drug targets. In this study, three-step classification models using different network topological properties were designed and implemented using support vector machine (SVM) to compare the enrichment of known drug targets from non-targets. Surprisingly, none of the models was able to identify more than 75% of the true targets in the test set. It appears that the currently used simple PPIN topological properties are not likely robust enough for prediction of potential drug targets with high confidence, which also echoes similarly unsatisfying prediction data reported previously. However, we proposed that quality and quantity improvement of the protein-protein interactions (PPI) data for model training will help increasing the prediction accuracy. PMID- 26552444 TI - Experimental evaluation of sand fly collection and storage methods for the isolation and molecular detection of Phlebotomus-borne viruses. AB - BACKGROUND: Several viruses have been recently isolated from Mediterranean phlebotomine sand flies; some are known to cause human disease while some are new to science. To monitor the Phlebotomus-borne viruses spreading, field studies are in progress using different sand fly collection and storage methods. Two main sampling techniques consist of CDC light traps, an attraction method allowing collection of live insects in which the virus is presumed to be fairly preserved, and sticky traps, an interception method suitable to collect dead specimens in high numbers, with a risk for virus viability or integrity. Sand flies storage requires a "deep cold chain" or specimen preservation in ethanol. In the present study the influence of sand fly collection and storage methods on viral isolation and RNA detection performances was evaluated experimentally. METHODS: Specimens of laboratory-reared Phlebotomus perniciosus were artificially fed with blood containing Toscana virus (family Bunyaviridae, genus Phlebovirus). Various collection and storage conditions of blood-fed females were evaluated to mimic field procedures using single and pool samples. Isolation on VERO cell cultures, quantitative Real time-Retro-transcriptase (RT)-PCR and Nested-RT-PCR were performed according to techniques commonly used in surveillance studies. RESULTS: Live engorged sand flies stored immediately at -80 degrees C were the most suitable sample for phlebovirus identification by both virus isolation and RNA detection. The viral isolation rate remained very high (26/28) for single dead engorged females frozen after 1 day, while it was moderate (10/30) for specimens collected by sticky traps maintained up to 3 days at room temperature and then stored frozen without ethanol. Opposed to viral isolation, molecular RNA detection kept very high on dead sand flies collected by sticky traps when left at room temperature up to 6 days post blood meal and then stored frozen in presence (88/95) or absence (87/88) of ethanol. Data were confirmed using sand fly pools. CONCLUSIONS: While the collection and storage methods investigated had not much impact on the ability to detect viral RNA by molecular methods, they affected the capacity to recover viable viruses. Consequently, sand fly collection and handling procedures should be established in advance depending on the goal of the surveillance studies. PMID- 26552445 TI - Amyloid beta-protein oligomers upregulate the beta-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons. AB - BACKGROUND: beta-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is a membrane-bound aspartyl protease that initiates amyloid beta-protein (Abeta) generation. Aberrant elevation of BACE1 levels in brains of Alzheimer's disease (AD) patients may involve Abeta. In the present study, we used a neuron culture model system to investigate the effects of Abeta on BACE1 expression as well as the underlying mechanisms. RESULTS: Rat primary cortical neurons were treated with relatively low concentrations (2.5 MUM) of Abeta42 oligomers (Abeta-O) or fibrils (Abeta-F) for 2-3 days. Abeta-O induced a significant increase in protein levels of BACE1, while Abeta-F only had a marginal effect. Levels of amyloid precursor protein (APP) and the major alpha-secretase, ADAM10, remained unaltered upon treatment with both types of Abeta. Abeta-O treatment resulted in activation of eIF2alpha and caspase 3 in a time-dependent manner, with no changes in the endoplasmic reticulum (ER) stress marker, GRP78, indicating that a typical ER stress response is not induced under our experimental conditions. Furthermore, Abeta-O did not affect BACE1 mRNA expression but augmented the levels of exogenous BACE1 expressed via recombinant adenoviruses, indicating regulation of BACE1 protein expression, not at the transcriptional or translational but the post-translational level. Immunocytochemical analysis revealed that Abeta-O causes a significant increase in BACE1 immunoreactivity in neurites (both axons and dendrites), but not soma of neurons; this change appears relevant to the mechanism of Abeta-O-induced BACE1 elevation, which may involve impairment of BACE1 trafficking and degradation. In contrast, Abeta-O had no effect on APP immunoreactivity. CONCLUSION: Our results collectively suggest that Abeta oligomers induce BACE1 elevation via a post-translational mechanism involving its altered subcellular distribution in neurons, which possibly triggers a vicious cycle of Abeta generation, thus contributing to the pathogenetic mechanism of AD. PMID- 26552446 TI - Supporting parents following pregnancy loss: a cross-sectional study of telephone peer supporters. AB - BACKGROUND: The death of a baby before or soon after birth can place an enormous psychological toll on parents. Parent support groups have grown in response to bereaved parents' unmet needs for support. Peer support is the hallmark of these organisations but little is known about the experiences of volunteers who provide support. This study examines the perceptions and experiences of parent support group volunteers who deliver a 24-h telephone support service for the Australian Stillbirth and Newborn Death Support (Sands) organisation in order to inform the ongoing development and sustainability of effective peer support. This parent-led organisation has delivered support to those affected by miscarriage, stillbirth and newborn death for more than 30 years. METHODS: Twenty-four Parent Supporters completed an online questionnaire. A mix of open- and closed questions asked about aspects of the Parent Supporter role. Quantitative data was summarised using descriptive statistics. Free-text responses to open-ended items were categorised and used to extend and illustrate the quantitative findings. RESULTS: Our findings reveal a group of highly dedicated and experienced volunteers who had taken 473 calls in the preceding 12 months. Calls were diverse but most were from bereaved mothers seeking 'to talk with someone who understands' in the early weeks and months after stillbirth or miscarriage. Most Parent Supporters indicated they felt well-prepared, confident, and satisfied in their role. Challenges include balancing the demands of the role and ongoing training and support. CONCLUSIONS: Peer volunteers contribute to addressing a significant need for support following pregnancy loss. Delivering and sustaining high quality parent-led support depends on volunteer recruitment and retention and this, in turn, requires organisational responses. PMID- 26552447 TI - High glucose induces renal tubular epithelial injury via Sirt1/NF-kappaB/microR 29/Keap1 signal pathway. AB - OBJECTIVE: Diabetic nephropathy (DN) is a serious complication that commonly confronted by diabetic patients. A common theory for the pathogenesis of this renal dysfunction in diabetes is cell injury, inflammation as well as oxidative stress. In this content, the detailed molecular mechanism underlying high glucose induced renal tubular epithelial injury was elaborated. METHODS: An in vivo rat model of diabetes by injecting streptozotocin (STZ) and an in vitro high glucose incubated renal tubular epithelial cell (HK-2) model were used. Expression levels of Keap1, nuclear Nrf2 and p65 were determined by western blotting. Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. Keap1 3'-UTR activity was detected using luciferase reporter gene assay. Cell viability was determined using MTT assay. RESULTS: In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. In high glucose incubated HK-2 cell, deacetylases activity of Sirt1 was attenuated that leads to decreased activity of nuclear factor kappa B (NF-kappaB). NF-kappaB was demonstrated to regulate miR-29 expression by directly binding to its promotor. The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. While high glucose induced down regulation of miR 29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability. CONCLUSION: High glucose induces renal tubular epithelial injury via Sirt1/NF-kappaB/microR 29/Keap1 signal pathway. PMID- 26552448 TI - Transcriptome profiling of differentially expressed genes in floral buds and flowers of male sterile and fertile lines in watermelon. AB - BACKGROUND: Male sterility is an important mechanism for the production of hybrid seeds in watermelon. Although fruit development has been studied extensively in watermelon, there are no reports on gene expression in floral organs. In this study, RNA-sequencing (RNA-seq) was performed in two near-isogenic watermelon lines (genic male sterile [GMS] line, DAH3615-MS and male fertile line, DAH3615) to identify the differentially expressed genes (DEGs) related to male sterility. RESULTS: DEG analysis showed that 1259 genes were significantly associated with male sterility at a FDR P-value of < 0.01. Most of these genes were only expressed in the male fertile line. In addition, 11 functional clusters were identified using DAVID functional classification analysis. Of detected genes in RNA-seq analysis, 19 were successfully validated by qRT-PCR. CONCLUSIONS: In this study, we carried out a comprehensive floral transcriptome sequence comparison of a male fertile line and its near-isogenic male sterile line in watermelon. This analysis revealed essential genes responsible for stamen development, including pollen development and pollen tube elongation, and allowed their functional classification. These results provided new information on global mechanisms related to male sterility in watermelon. PMID- 26552449 TI - Risk factors for lumbar intervertebral disc height narrowing: a population-based longitudinal study in the elderly. AB - BACKGROUND: The progression of disc degeneration is generally believed to be associated with low back pain and/or degenerative lumbar diseases, especially in the elderly. The purpose of this study was to quantitatively evaluate changes in lumbar disc height using radiographic measurements and to investigate risk factors for development of disc height narrowing of the elderly. METHODS: From 1997 to 2007, 197 village inhabitants at least 65 years-old who participated in baseline examinations and more than four follow-up examinations conducted every second year were chosen as subjects for this study. Using lateral lumbar spine radiographs of each subject, L1-L2 to L5-S1 disc heights were measured. The subjects were divided into two groups according to the rate of change in disc height: mildly decreased (<=20 % decrease) and severely decreased (>20 % decrease). A stepwise multiple logistic regression analysis was used to select those factors significantly associated with disc height narrowing. RESULTS: Disc height at each intervertebral disc (IVD) level decreased gradually over ten years (p < 0.01, an average 5.8 % decrease of all disc levels). There was no significant difference in the rate of change in disc height among the IVD levels. Female gender, radiographic knee osteoarthritis and low back pain at baseline were associated with increased risk for disc height narrowing. CONCLUSIONS: We conducted the first population-based cohort study of the elderly that quantitatively evaluated lumbar disc height using radiographic measurements. The risk factors identified in this study would contribute to a further understanding the pathology of disc degeneration. PMID- 26552450 TI - Is screening and surveillance for early detection of gastric cancer needed in Korean Americans? AB - The incidence rate of gastric cancer in Korean Americans is over five times higher than that in non-Hispanic whites, and is similar to the incidence of colorectal cancer in the overall United States population. In Korea, the National Cancer Screening Program recommends endoscopy or upper gastrointestinal series for people aged 40 years and older every 2 years. However, the benefit of gastric cancer screening in Korean Americans has not been evaluated. Based on epidemiologic studies, Korean Americans appear to have more similar gastric cancer risk factors to Koreans as opposed to Americans of European descent, though the risk of gastric cancer appears to decrease for subsequent generations. Therefore, in accordance with recent recommendations regarding screening for gastric cancer in Korea, endoscopic screening for gastric cancer in Korean Americans should be considered, especially in those with known atrophic gastritis/intestinal metaplasia or a family history of gastric cancer. In the future, additional studies will needed to assess whether a screening program for gastric cancer in Korean Americans will result in a survival benefit. PMID- 26552451 TI - Role of dipeptidyl peptidase-4 inhibitors in new-onset diabetes after transplantation. AB - Despite strict pre- and post-transplantation screening, the incidence of new onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT. PMID- 26552453 TI - Time to learn from the past and prepare for the future in Helicobacter pylori eradication. PMID- 26552452 TI - Guidelines for the management of myeloproliferative neoplasms. AB - Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are collectively known as 'Philadelphia-negative classical myeloproliferative neoplasms (MPNs).' The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs. Currently, the JAK2 mutation is not only a standard criterion for diagnosis but is also a new target for drug development. The JAK1/2 inhibitor, ruxolitinib, was the first JAK inhibitor approved for patients with intermediate- to high-risk myelofibrosis and its effects in improving symptoms and survival benefits were demonstrated by randomized controlled trials. In 2011, the Korean Society of Hematology MPN Working Party devised diagnostic and therapeutic guidelines for Korean MPN patients. Subsequently, other genetic mutations have been discovered and many kinds of new drugs are now under clinical investigation. In view of recent developments, we have revised the guidelines for the diagnosis and management of MPN based on published evidence and the experiences of the expert panel. Here we describe the epidemiology, new genetic mutations, and novel therapeutic options as well as diagnostic criteria and standard treatment strategies for MPN patients in Korea. PMID- 26552454 TI - Incidence of and risk factors for thyroid dysfunction during peginterferon alpha and ribavirin treatment in patients with chronic hepatitis C. AB - BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD. PMID- 26552455 TI - Trends in Helicobacter pylori eradication rates by first-line triple therapy and related factors in eradication therapy. AB - BACKGROUND/AIMS: Trends in successful eradication of Helicobacter pylori using first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin, and clarithromycin, have been understudied. We evaluated H. pylori eradication rates at a single center over the last 10 years and identified risk factors related to eradication failure. METHODS: This study included 1,413 patients who were diagnosed with H. pylori infection and received 7 days of triple therapy between January 2003 and December 2012. We investigated H. pylori eradication rates retrospectively with respect to the year of therapy, as well as demographic and clinical factors. H. pylori eradication was confirmed by a (13)C-urea breath test or a rapid urease test at least 4 weeks after the completion of triple therapy. RESULTS: The overall H. pylori eradication rate was 84.9%. Annual eradication rates from 2003 to 2012 were 93.5%, 80.0%, 87.2%, 88.5%, 92.0%, 88.3%, 85.7%, 84.1%, 83.7%, and 78.8%, respectively, by per-protocol analysis. The eradication rate with first-line triple therapy decreased during the last 10 years (p = 0.015). Multivariate analysis showed that female gender (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.12 to 2.55) and smoking (OR, 1.61; 95% CI, 1.05 to 2.47) were associated with the failure of H. pylori eradication therapy. CONCLUSIONS: The efficacy of first-line triple therapy for H. pylori infection has decreased over the last 10 years, suggesting an increase in antibiotic-resistant H. pylori strains. Thus, other first-line therapies may be necessary for H. pylori eradication in the near future. PMID- 26552456 TI - Interatrial septal thickness as a marker of structural and functional remodeling of the left atrium in patients with atrial fibrillation. AB - BACKGROUND/AIMS: There have been reports that interatrial septal (IAS) thickness is increased in patients with atrial fibrillation (AF). This study was performed to investigate whether IAS thickness determined by transthoracic echocardiography (TTE) represents the amount of left atrium (LA) structural and functional remodeling. METHODS: The study population consisted of 104 consecutive patients who underwent catheter ablation (CA) for AF (paroxysmal atrial fibrillation [PAF], 82; persistent atrial fibrillation [PeAF], 22). IAS thickness and left atrium volume (LAV) using TTE, and LA voltage (LA(VOL)) using 3-dimensional electroanatomical mapping system were assessed during sinus rhythm. RESULTS: IAS thickness was significantly correlated with maximal LAV (LAV(max)) (r = 0.288, p = 0.003), mean LA(VOL) (r = -0.537, p < 0.001), total left atrium emptying fraction (LAEF(total); r = -0.213, p = 0.030), and active LAEF (LAEF(active); r = -0.249, p = 0.014). IAS thickness was greater in the high-risk group (>= 2) compared to other groups according to CHA2DS2-VASc score (p = 0.019). During a follow-up of 19.6 months, 23 subjects (22.1%; PAF, 17; PeAF, 6) had recurrence of arrhythmia. Univariate analysis showed that LAV(max), minimal LAV, mean LA(VOL), LVEF(total), LVEF(active), and IAS thickness were associated with recurrence of arrhythmia. However, on multivariate analysis, only mean LA(VOL) and LAEF(active) were independent risk factors for recurrence. CONCLUSIONS: Although IAS thickness showed significant correlations with parameters for LA structural and functional remodeling, this parameter alone could not independently predict recurrence of arrhythmia after CA for AF. PMID- 26552457 TI - Temporal trends and in-hospital outcomes of primary percutaneous coronary intervention in nonagenarians with ST-segment elevation myocardial infarction. AB - BACKGROUND/AIMS: Data regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in nonagenarians are very limited. The aim of the present study was to evaluate the temporal trends and in-hospital outcomes of primary PCI in nonagenarian STEMI patients. METHODS: We retrospectively reviewed data from the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to January 2008, and from the Korea Working Group on Myocardial Infarction (KorMI) from February 2008 to May 2010. RESULTS: During this period, the proportion of nonagenarians among STEMI patients more than doubled (0.59% in KAMIR vs. 1.35% in KorMI), and the rate of use of primary PCI also increased (from 62.5% in KAMIR to 81.0% in KorMI). We identified 84 eligible study patients for which the overall in hospital mortality rate was 21.4% (25.0% in KAMIR vs. 20.3% in KorMI, p = 0.919). Multivariate analysis identified two independent predictors of in-hospital mortality, namely a final Thrombolysis in Myocardial Infarction (TIMI) flow < 3 (odds ratio [OR], 13.7; 95% confidence interval [CI], 3.2 to 59.0; p < 0.001) and cardiogenic shock during hospitalization (OR, 6.7; 95% CI, 1.5 to 30.3; p = 0.013). CONCLUSIONS: The number of nonagenarian STEMI patients who have undergone primary PCI has increased. Although a final TIMI flow < 3 and cardiogenic shock are independent predictors of in-hospital mortality, primary PCI can be performed with a high success rate and an acceptable in-hospital mortality rate. PMID- 26552458 TI - Clinical manifestations of pneumonia according to the causative organism in patients in the intensive care unit. AB - BACKGROUND/AIMS: Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. METHODS: A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. RESULTS: The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. CONCLUSIONS: Neither the causative micro organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification. PMID- 26552459 TI - Survival benefits of warfarin in Korean patients with idiopathic pulmonary arterial hypertension. AB - BACKGROUND/AIMS: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease with high mortality. Although most studies recommend anticoagulation treatment for IPAH, the benefits are uncertain, particularly in Korea, where it has not been studied. The purpose of this study was to evaluate survival outcomes of Korean patients with IPAH treated with warfarin. METHODS: We performed a retrospective cohort study of patients diagnosed previously with pulmonary arterial hypertension (PAH) at the Asan Medical Center in Korea, between January 1994 and February 2013. We excluded patients with associated PAH, patients who did not undergo right heart catheterization (RHC), and patients with a positive vasoreactivity test. Patients in the study cohort were classified into a "warfarin group" and a "non-warfarin group," according to the treatment they received during the first year after diagnosis. RESULTS: We identified 31 patients with IPAH and a negative vasoreactivity test on RHC. Median patient age was 36.0 years, and 23 patients (74.2%) were female. The median time from the onset of symptoms to diagnosis was 19.0 months, and the most common presenting symptom was dyspnea. Survival rates of the patients at 1, 3, 5, and 10 years were 90.2%, 79.5%, 62.7%, and 34.8%, respectively. The mean survival period was 12.0 years in the warfarin group and 6.1 years in the non-warfarin group. Warfarin treatment had significant survival benefits in patients with IPAH (p = 0.023). CONCLUSIONS: Warfarin treatment substantially improved survival outcomes in Korean cases of IPAH. PMID- 26552460 TI - Obstructive sleep apnea with excessive daytime sleepiness is associated with non alcoholic fatty liver disease regardless of visceral fat. AB - BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is associated with an increased risk of obesity and non-alcoholic fatty liver disease (NAFLD), but it remains unclear whether the risk of NAFLD is independently related to OSA regardless of visceral obesity. Thus, the aim of the present study was to examine whether OSA alone or in combination with excessive daytime sleepiness (EDS) or short sleep duration was associated with NAFLD independent of visceral fat in Korean adults. METHODS: A total of 621 participants were selected from the Korean Genome and Epidemiology Study (KoGES). The abdominal visceral fat area (VFA) and hepatic fat components of the participants were assessed using computed tomography scans and they were then categorized into four groups depending on the presence of OSA and EDS. RESULTS: The proportions of NAFLD were 21.1%, 18.5%, 32.4%, and 46.7% in participants without OSA/EDS, with only EDS, with only OSA, and with both OSA and EDS, respectively. A combination of OSA and EDS increased the odds ratio (OR) for developing NAFLD (OR, 2.75; 95% confidence interval [CI], 1.21 to 6.28) compared to those without OSA/EDS, and this association remained significant (OR, 2.38; 95% CI, 1.01 to 5.59) even after adjusting for VFA. In short sleepers (< 5 hours) with OSA, the adjusted OR for NAFLD was 2.50 (95% CI, 1.08 to 5.75) compared to those sleeping longer than 5 hours without OSA. CONCLUSIONS: In the present study, OSA was closely associated with NAFLD in Korean adults. This association was particularly strong in those with EDS or short sleep duration regardless of VFA. PMID- 26552461 TI - Predicting postoperative total calcium requirements after parathyroidectomy in secondary hyperparathyroidism. AB - BACKGROUND/AIMS: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. METHODS: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. RESULTS: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Deltaphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. CONCLUSIONS: Preoperative ALP, preoperative iPTH, and Deltaphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization. PMID- 26552462 TI - Risk factors in the progression of BK virus-associated nephropathy in renal transplant recipients. AB - BACKGROUND/AIMS: BK virus-associated nephropathy (BKVAN) is an important cause of allograft dysfunction in kidney transplant recipients. It has an unfavorable clinical course, and no definite treatment guidelines have yet been established. Here, we report our center's experience with biopsy-proven BKVAN and investigate factors associated with its progression. METHODS: From January 2004 to April 2013, 25 patients with BKVAN were diagnosed by biopsy at Seoul St. Mary's Hospital. Of the 25 patients, 10 were deceased-donor transplant recipients and 15 were living-donor transplant recipients. Three of the patients underwent retransplantation. The primary immunosuppressant used was tacrolimus in 17 patients and cyclosporine in eight patients. RESULTS: BKVAN was observed at a mean duration of 22.8 +/- 29.1 months after transplantation. The mean serum creatinine level at biopsy was 2.2 +/- 0.7 mg/dL. BKVAN occurred with acute rejection in eight patients (28%). Immunosuppression modification was performed in 21 patients (84%). Additionally, leflunomide and intravenous immunoglobulin were administered to 13 patients (52%) and two (8%), respectively. Allograft loss occurred in five patients (27.8%) during the follow- up period at 0.7, 17.1, 21.8, 39.8, and 41.5 months after the BKVAN diagnosis. Advanced stages of BKVAN, increased creatinine levels, and accompanying acute rejection at the time of BKVAN diagnosis increased the risk of allograft failure. CONCLUSIONS: The clinical outcomes in patients with biopsy-proven BKVAN were unfavorable in the present study, especially in patients with advanced-stage BKVAN, poor renal function, and acute allograft rejection. PMID- 26552463 TI - The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells. AB - BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene. PMID- 26552464 TI - Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia. AB - BACKGROUND/AIMS: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis. METHODS: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012. RESULTS: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS). CONCLUSIONS: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS. PMID- 26552465 TI - Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure. AB - BACKGROUND/AIMS: The purpose of this study was to identify predictive factors for erlotinib treatment in non-small cell lung cancer (NSCLC) patients following gefitinib failure. METHODS: Forty-five patients with NSCLC who were treated with erlotinib following gefitinib failure at Seoul National University Hospital between August 2005 and November 2011 were enrolled. Epidermal growth factor receptor (EGFR) mutation status, pathologic findings and other clinical factors, including response to tyrosine kinase inhibitors (TKIs) and progression-free survival (PFS), were evaluated. RESULTS: Of the 45 patients, 40 patients (88.8%) had adenocarcinoma. The following EGFR mutations were observed: five patients with a deletion of exon 19, six patients with an L858R mutation, three patients with wild-type EGFR, and 31 patients with unknown mutations. The response rate of erlotinib was 4.4%, and stable disease was 42.2%. The median PFS for erlotinib was 2.6 months (95% confidence interval, 1.4 to 3.7). Patients with a PFS >= 4 months during previous gefitinib treatment had a significantly longer PFS with erlotinib (3.3 months vs. 1.6 months, respectively; p < 0.01) than patients with PFS < 4 months with gefitinib. According to multivariate analyses, PFS >= 4 months for previous gefitinib treatment was significantly associated with prolonged PFS with erlotinib (p = 0.04). However, the response rate of gefitinib and treatment sequence were not associated with prolonged PFS with erlotinib (p = 0.28 and p = 0.67, respectively). CONCLUSIONS: Following rechallenge with the EGFR TKI erlotinib following gefitinib failure, patients who showed prolonged PFS with gefitinib benefit from erlotinib. However, further prospective studies are needed to confirm these findings. PMID- 26552466 TI - Serum galactomannan levels in the diagnosis of invasive aspergillosis. AB - BACKGROUND/AIMS: In this study, the sensitivity-specificity of galactomannan enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated. METHODS: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined. RESULTS: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA >= 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results. CONCLUSIONS: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected. PMID- 26552467 TI - Factors related to outcomes in lupus-related protein-losing enteropathy. AB - BACKGROUND/AIMS: Protein-losing enteropathy (PLE), characterized by severe hypoalbuminemia and peripheral edema, is a rare manifestation of systemic lupus erythematosus. This present study aimed to identify the distinctive features of lupus-related PLE and evaluate the factors related to the treatment response. METHODS: From March 1998 to March 2014, the clinical data of 14 patients with lupus PLE and seven patients with idiopathic PLE from a tertiary center were reviewed. PLE was defined as a demonstration of protein leakage from the gastrointestinal tract by either technetium 99m-labelled human albumin scanning or fecal alpha1-antitrypsin clearance. A positive steroid response was defined as a return of serum albumin to >= 3.0 g/dL within 4 weeks after initial steroid monotherapy, and remission as maintenance of serum albumin >= 3.0 g/dL for at least 3 months. A high serum total cholesterol level was defined as a level of >= 240 mg/dL. RESULTS: The mean age of the lupus-related PLE patients was 37.0 years, and the mean follow-up duration was 55.8 months. Significantly higher erythrocyte sedimentation rate and serum total cholesterol levels were found for lupus PLE than for idiopathic PLE. Among the 14 patients with lupus PLE, eight experienced a positive steroid response, and the serum total cholesterol level was significantly higher in the positive steroid response group. A positive steroid response was associated with an initial high serum total cholesterol level and achievement of remission within 6 months. CONCLUSIONS: In lupus-related PLE, a high serum total cholesterol level could be a predictive factor for the initial steroid response, indicating a good response to steroid therapy alone. PMID- 26552468 TI - Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population. AB - BACKGROUND/AIMS: Gout is a common inf lammatory arthritis triggered by the crystallization of uric acid in the joints. Serum uric acid levels are highly heritable, suggesting a strong genetic component. Independent studies to confirm the genetic associations with gout in various ethnic populations are warranted. We investigated the association of polymorphisms in the ABCG2 and SLC2A9 genes with gout in Korean patients and healthy individuals. METHODS: We consecutively enrolled 109 patients with gout and 102 healthy controls. The diagnosis of gout was based on the preliminary criteria of the America College of Rheumatology. Genomic DNA was extracted from whole blood samples. We identified single nucleotide polymorphism (SNP) changes in the ABCG2 and SLC2A9 genes using a direct sequencing technique. rs2231142 in ABCG2 and rs6449213 and rs16890979 in SLC2A9 and nearby regions were amplified by polymerase chain reaction. RESULTS: Patients with gout had significantly higher A/A genotype (29.3% vs. 4.9%, respectively) and A allele (52.8% vs. 26.5%, respectively) frequencies of rs2231142 in ABCG2 than did controls (chi(2) = 29.42, p < 0.001; odds ratio, 3.32; 95% confidence interval, 2.11 to 5.20). We found novel polymorphisms (c.881A>G and c.1002+78G>A) in the SLC2A9 gene. The univariate logistic regression analysis revealed that the c.881A>G and c.1002+78G>A SNPs were significantly higher in patients than in controls. CONCLUSIONS: We demonstrated a significant association between rs2231142 in the ABCG2 gene and gout and identified novel SNPs, c.881A>G and c.1002+78G>A, in the SLC2A9 gene that may be associated with gout in a Korean population. PMID- 26552469 TI - Acute myocardial infarction caused by a floating thrombus in the proximal ascending aorta. PMID- 26552470 TI - Fabry disease previously diagnosed as Henoch-Schonlein purpura. PMID- 26552471 TI - Bone metastasis in pulmonary sclerosing hemangioma. PMID- 26552472 TI - Long-term survival after concurrent chemoradiation therapy for esophageal cancer with tracheal invasion. PMID- 26552473 TI - Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman. PMID- 26552474 TI - Nutmeg liver cardiac cirrhosis caused by constrictive pericarditis. PMID- 26552475 TI - Extreme septal hypertrophy in an adolescent with congenital familial hypertrophic cardiomyopathy. PMID- 26552476 TI - Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes. AB - BACKGROUND: Complement is a large protein network in plasma that is crucial for human immune defenses and a major cause of aberrant inflammatory reactions. The C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically important products. So far, it has been difficult to study the exact molecular arrangement of C5 convertases, because their non-catalytic subunits (C3b) are covalently linked to biological surfaces through a reactive thioester. Through development of a highly purified model system for C5 convertases, we here aim to provide insights into the surface specific nature of these important protease complexes. RESULTS: Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules. Site-specific biotinylation of C3b via the thioester allowed binding of C3b in the natural orientation on the surface. In the presence of factor B and factor D, these C3b beads could effectively convert C5. Conversion rates of surface-bound C3b were more than 100-fold higher than fluid-phase C3b, confirming the requirement of a surface. We determine that high surface densities of C3b, and its attachment via the thioester, are essential for C5 convertase formation. Combining our results with molecular modeling explains how high C3b densities may facilitate intermolecular interactions that only occur on target surfaces. Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. CONCLUSIONS: We establish a highly purified model that mimics the natural arrangement of C5 convertases on a surface. The developed model and molecular insights are essential to understand the molecular basis of deregulated complement activity in human disease and will facilitate future design of therapeutic interventions against these critical enzymes in inflammation. PMID- 26552477 TI - Androgen receptor status is highly conserved during tumor progression of breast cancer. AB - BACKGROUND: With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. METHODS: AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells >=1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. RESULTS: AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). CONCLUSIONS: Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended. PMID- 26552479 TI - Speed of flea knockdown of spinosad compared to afoxolaner, and of spinosad through 28 days post-treatment in controlled laboratory studies. AB - BACKGROUND: The speed of flea knockdown by different products and their duration of effectiveness are factors which affect veterinarian prescribing decisions. To further validate the month-long pulicidal effectiveness of spinosad and determine its rate of flea knockdown to that of afoxolaner, three studies were conducted in two laboratories in the United States, utilizing flea infestations from colonies which are regularly refreshed through introduction of locally caught fleas. METHODS: All study assessors were blinded, dogs were ranked by pre-study flea counts and randomized accordingly, and treatments administered on Day 0. All studies included a negative control group; two also included an afoxolaner group. In one study, flea challenges for treated and control dogs (10 per group) were completed 21 and 28 days after treatment and counts were performed 24 h later. In each of two speed-of-knockdown (SOK) studies, 36 dogs were randomized, six dogs per group, to: untreated controls; administered oral afoxolaner (2.6-6.2 mg/kg); or oral spinosad (32.1-59.2 mg/kg). In the SOK studies, live fleas from Day -1 infestations were counted after being combed off at 1 and 3 h after treatment, and after reinfestations on Day 7. RESULTS: There were no treatment-related adverse events. Spinosad was 98.6% effective at 28 days post treatment. For SOK, geometric mean live flea counts for afoxolaner were not different from controls at any assessment. For spinosad, all mean counts were significantly lower than in controls (p <= 0.0128) except at 1 h post treatment in both studies. Spinosad was significantly more effective than afoxolaner in both studies at 3 h post treatment (p <= 0.0065) and post-Day 7 infestation (p <= 0.0054), and at 1 h post treatment (p = 0.0276) and post-Day 7 infestation in one study. CONCLUSIONS: These data validate spinosad's faster onset of flea knockdown than afoxolaner against infestations present at the time of treatment, and faster residual speed of flea knockdown for at least 7 days post treatment, and confirm spinosad's extended residual speed of kill for at least 28 days post treatment. PMID- 26552478 TI - Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women. AB - BACKGROUND: To determine reference intervals for serum levels of human epididymis protein 4 (HE4) in Chinese women. METHODS: In this multicenter (n = 9) study, 618 healthy women, 767 patients with non-malignant diseases, and 951 patients with malignant tumors were enrolled. Serum levels of HE4 were measured in all patients using electrochemiluminescence immunoassays. The influence of age, menopause, malignancy status and other characteristics on the levels of HE4 was evaluated using univariate and multivariate analyses. Confidence intervals (2.5-97.5 %) were determined in different populations. RESULTS: There were significant differences in HE4 levels among groups with different ages, menopause or malignancy status. Higher levels of HE4 were detected in elder compared to younger, post- compare to pre- menopause and malignant compared to benign subjects. Multivariate analysis showed that menopause and malignancy status, as well as smoking and pelvic masses were independent factors involved in serum HE4 levels. In pre-menopause stage, the reference ranges of HE4 level were 29.30 68.79, 28.12-1284.83 and 34.75-981.91 pmol/L in healthy, benign and malignant populations, respectively. In post-menopause stage, the reference ranges are 35.96-114.43, 39.11-2208.70 and 39.40-1678.13 pmol/L for those populations. CONCLUSIONS: The present study has established the reference intervals of HE4 levels in pre- and post-menopause populations with different malignancy status. PMID- 26552481 TI - Recent trends and advancements in bioassay based on bioluminescent technologies. PMID- 26552480 TI - Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation. AB - BACKGROUND: Endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs). We aimed at characterizing these two EPC subtypes and at identifying their role in platelet aggregation. METHODS: EOCs and ECFCs were generated from human peripheral blood mononuclear cells (PBMCs) seeded in conditioned media on fibronectin and collagen, respectively. The morphological, phenotypical and functional characteristics of EOCs and ECFCs were assessed by optical and confocal laser scanning microscopes, cell surface markers expression, and Matrigel tube formation. The impact of EOCs and ECFCs on platelet aggregation was monitored in collagen-induced optical aggregometry and compared with PBMCs and human umbilical vein endothelial cells (HUVECs). The levels of the anti-platelet agents' nitric oxide (NO) and prostacyclin (PGI2) released from cultured cells as well as the expression of their respective producing enzymes NO synthases (NOS) and cyclooxygenases (COX) were also assessed. RESULTS: We showed that EOCs display a monocytic-like phenotype whereas ECFCs have an endothelial-like phenotype. We demonstrated that both EOCs and ECFCs and their supernatants inhibited platelet aggregation; however ECFCs were more efficient than EOCs. This could be related to the release of significantly higher amounts of NO and PGI2 from ECFCs, in comparison to EOCs. Indeed, ECFCs, like HUVECs, constitutively express the endothelial (eNOS)-and inducible (iNOS)-NOS isoforms, and COX-1 and weakly express COX-2, whereas EOCs do not constitutively express these NO and PGI2 producing enzymes. CONCLUSION: The different morphological, phenotypic and more importantly the release of the anti-aggregating agents PGI2 and NO in each EPC subtype are implicated in their respective roles in platelet function and thus, may be linked to the increased efficiency of ECFCs in inhibiting platelet aggregation as compared to EOCs. PMID- 26552482 TI - The triple threat of pregnancy, HIV infection and malaria: reported causes of maternal mortality in two nationwide health facility assessments in Mozambique, 2007 and 2012. AB - BACKGROUND: The paper's primary purpose is to determine changes in magnitude and causes of institutional maternal mortality in Mozambique. We also describe shifts in the location of institutional deaths and changes in availability of prevention and treatment measures for malaria and HIV infection. METHODS: Two national cross sectional assessments of health facilities with childbirth services were conducted in 2007 and 2012. Each collected retrospective data on deliveries and maternal deaths and their causes. In 2007, 2,199 cases of maternal deaths were documented over a 12 month period; in 2012, 459 cases were identified over a three month period. In 2007, data collection also included reviews of maternal deaths when records were available (n = 712). RESULTS: Institutional maternal mortality declined from 541 to 284/100,000 births from 2007 to 2012. The rate of decline among women dying of direct causes was 66% compared to 26% among women dying of indirect causes. Cause-specific mortality ratios fell for all direct causes. Patterns among indirect causes were less conclusive given differences in cause-of-death recording. In absolute numbers, the combination of antepartum and postpartum hemorrhage was the leading direct cause of death each year and HIV and malaria the main non-obstetric causes. Based on maternal death reviews, evidence of HIV infection, malaria or anemia was found in more than 40% of maternal deaths due to abortion, ectopic pregnancy and sepsis. Almost half (49%) of all institutional maternal deaths took place in the largest hospitals in 2007 while in 2012, only 24% occurred in these hospitals. The availability of antiretrovirals and antimalarials increased in all types of facilities, but increases were most dramatic in health centers. CONCLUSIONS: The rate at which women died of direct causes in Mozambique's health facilities appears to have declined significantly. Despite a clear improvement in access to antiretrovirals and antimalarials, especially at lower levels of health care, malaria, HIV, and anemia continue to exact a heavy toll on child-bearing women. Going forward, efforts to end preventable maternal and newborn deaths must maximize the use of antenatal care that includes integrated preventive/treatment options for HIV infection, malaria and anemia. PMID- 26552483 TI - Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies? AB - The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments. PMID- 26552484 TI - Identification and characterization of human nucleus pulposus cell specific serotypes of adeno-associated virus for gene therapeutic approaches of intervertebral disc disorders. AB - BACKGROUND: Intervertebral disc (IVD) disorders are often accompanied by painful inflammatory and immunopathological processes. Nucleus pulposus (NP) cells play a pivotal role in maintenance of IVD by organizing the expression of anabolic, catabolic, anti-catabolic and inflammatory cytokines. Human NP cells have been targeted by gene therapeutic approaches using lentiviral or adenoviral systems that could be critical due to genome incorporation or immunological side effects. Adeno-associated viruses (AAVs), which do not express any viral gene and are not linked with any known disease in humans, are attractive gene delivery vectors. However, their lack of specific tissue tropism and preexisting immune response are main problems for therapeutic applications. Heretofore, AAVs have not been studied in human IVD research. Therefore, we attempted to identify NP cell specific AAV serotype by targeting human NP cells with different self complementary AAV (scAAV) serotypes. Identification and characterization of the proper serotype is crucial to establish less immunogenic and safer gene therapeutic approaches of IVD disorders. METHODS: Preoperative magnetic resonance imaging (MRI) was used for grading of IVD degeneration. NP cells were isolated, cultured with low-glucose and transduced with green fluorescent protein (GFP) packing scAAV serotypes (scAAV1-8) in a dose-dependent manner. scAAV titers were determined by quantitative polymerase chain reaction (qPCR). Transduction efficiencies were determined by fluorescence microscopy and fluorescence activated cell sorting within 48 days of post-transduction. The 3-(4, 5 dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine NP cell viability. Three-dimensional (3D) cell culture and enzyme linked immunosorbant assay (ELISA) were performed to examine the expression levels of inflammatory, catabolic and matrix proteins in NP cells. RESULTS: scAAV6, scAAV2 and scAAV3 showed high and prolonged transgene GFP expressions with transdution efficiencies of 98.6 %, 91.5 % and 89.6 % respectively (p <= 0.002). Unlike scAAV6, the serotypes scAAV2 and scAAV3 declined the viability of NP cells by about 25 % and 10 % respectively (p <= 0.001). Moreover, scAAV6 did not affect the expression of the inflammatory, catabolic and matrix proteins. CONCLUSIONS: As original primary research evaluating AAVs in degenerative human IVDs, this study identified scAAV6 as a proper serotype for high, stable and non immunogenic target gene expression in human NP cells. The data could be very important to design efficient and safer gene therapeutic approaches of IVD disorders. PMID- 26552485 TI - From knowing our needs to enacting change: findings from community consultations with indigenous communities in Bangladesh. AB - INTRODUCTION: Indigenous peoples are among the most marginalized peoples in the world due to issues relating to well-being, political representation, and economic production. The research consortium Goals and Governance for Global Health (Go4Health) conducted a community consultation process among marginalized groups across the global South aimed at including their voices in the global discourse around health in the post-2015 development agenda. This paper presents findings from the consultations carried out among indigenous communities in Bangladesh. METHODS: For this qualitative study, our research team consulted the Tripura and Mro communities in Bandarban district living in the isolated Chittagong Hill Tracts region. Community members, leaders, and key informants working in health service delivery were interviewed. Data was analyzed using thematic analysis. FINDINGS: Our findings show that remoteness shapes the daily lives of the communities, and their lack of access to natural resources and basic services prevents them from following health promotion messages. The communities feel that their needs are impossible to secure in a politically indifferent and sometimes hostile environment. CONCLUSION: Communities are keen to participate and work with duty bearers in creating the conditions that will lead to their improved quality of life. Clear policies that recognize the status of indigenous peoples are necessary in the Bangladeshi context to allow for the development of services and infrastructure. PMID- 26552486 TI - Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events. AB - BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB. METHODS: Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NFkappaB by Electrophorectic mobility shift assay (EMSA). RESULTS: We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NFkappaB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease. CONCLUSION: To the best of our knowledge, this is the first study to investigate effect of Ag85A and ESAT-6 on TCR- and TCR/CD28- induced upstream and downstream signalling events of T-cell activation in TB patients. This study showed the effect of secretory antigens of M. tuberculosis in the modulation of T cell signalling pathways. This inflection is accomplished by altering the proximal and distal events of signalling cascade which could be involved in T-cell dysfunctioning during the progression of the disease. PMID- 26552487 TI - Levels of circulating endothelial cells are low in idiopathic pulmonary fibrosis and are further reduced by anti-fibrotic treatments. AB - BACKGROUND: It has been suggested that circulating fibrocytes and endothelial cells actively participate in the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis (IPF). Indeed, fibrotic areas exist that have fewer blood vessels, whereas adjacent non-fibrotic tissue is highly vascularized. The number of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair. Thus, fibrocytes as well as endothelial cells could potentially be used as biomarkers of disease progression and treatment outcome. METHODS: Peripheral blood samples were collected from 67 patients with a multidisciplinary diagnosis of IPF and from 45 age-matched and sex-matched healthy volunteers. Buffy coat was isolated according to standard procedures and at least 20 million cells were stained with different monoclonal antibodies for the detection of CEC, EPC and circulating fibrocytes. For the detection of CEC and EPC, cells were stained with anti-CD45, anti-CD34, anti-CD133, anti-CD14, anti-CD309 and with the viability probe Far-Red LIVE/DEAD. For the detection of circulating fibrocytes, cells were first stained with LIVE/DEAD and the following monoclonal antibodies: anti-CD3, anti-CD19, anti-CD45, anti-CD34 and anti-CD14, then cells were fixed, permeabilized and stained with fluorochrome-conjugated anti-collagen I monoclonal antibodies. RESULTS: Patients with IPF displayed almost undetectable levels of circulating fibrocytes, low levels of CEC, and normal levels of EPC. Patients treated with nintedanib displayed higher levels of CEC, but lower levels of endothelial cells expressing CD309 (the type II receptor for vascular endothelial growth factor). Treatment with both nintedanib and pirfenidone reduced the percentage of CEC and circulating fibrocytes. CONCLUSIONS: Levels of CEC were reduced in patients with IPF as compared to healthy individuals. The anti-fibrotic treatments nintedanib and pirfenidone further reduced CEC levels. These findings might help explain the mechanism of action of these drugs and should be explored as predictive biomarkers in IPF. PMID- 26552489 TI - Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation. AB - Despite the presence of toll like receptor (TLR) expression in conventional TCRalphabeta T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H 2(b)) -> B6D2F1 (H-2(b/d)), recipients received transplants of wild type (WT) T cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type (H-2(d)) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-gamma or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-gamma producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT. PMID- 26552490 TI - Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease. AB - Mucosal-associated invariant T (MAIT) cells have been reported to play an important role in mucosal immunity. However, little is known about the roles of MAIT cells in chronic obstructive pulmonary disease (COPD). The aims of this study were to examine the levels of circulating MAIT cells and their subsets in COPD patients and to investigate the potential relationship between clinical parameters and MAIT cell levels. Forty-five COPD patients and 57 healthy control subjects were enrolled in the study. Circulating MAIT cells and their subset levels in the peripheral blood were measured by flow cytometry. Disease grades were classified according to the GOLD criteria for the assessment of severity of COPD. Circulating MAIT cell levels were found to be significantly reduced in COPD patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets. Interestingly, elevated serum C-reactive protein level and reduced FEV1/FVC ratio were associated with MAIT cell deficiency in COPD patients. Furthermore, the circulating MAIT levels were found to be significantly lower in patients with moderate to severe COPD than in patients with mild COPD. Our data shows that MAIT cells are numerically deficient in the peripheral blood of patients with COPD. In addition, this MAIT cell deficiency was found to reflect inflammatory activity and disease severity. These findings provide important information for monitoring the changes in MAIT cell levels and for predicting the prognosis during the disease course. PMID- 26552488 TI - Functions of TET Proteins in Hematopoietic Transformation. AB - DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5 hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti cancer agents. PMID- 26552491 TI - Dermatologic care of institutionalized elderly patients: a survey among dermatologists in the Netherlands. AB - BACKGROUND: dermatologists are expected to be increasingly confronted with institutionalized elderly patients, due to the rapidly ageing world population. OBJECTIVES: to determine the proportion of dermatologists visiting patients in nursing homes, together with the reasons for consultation, barriers to perform these visits and diagnostic and treatment patterns. MATERIALS & METHODS: a web based questionnaire regarding dermatologic care in nursing home patients was developed by a multidisciplinary group of dermatologists, residents and elderly care physicians. A cover letter containing a link to the final questionnaire was sent by e-mail to all 661 dermatologists and dermatology residents in the Netherlands. RESULTS: a total of 130 eligible questionnaires were returned (19.7%). Most respondents (79.2%) never had contact with an elderly care physician concerning a nursing home patient. However, only 30.0% of the respondents ever visited a patient within a nursing home. The most common reasons for nursing home visits were cutaneous (pre)malignancies (51.4%), eczema/dermatitis (25.7%) and (pressure) ulcers (8.6%). The most important barriers mentioned to perform nursing home visits were a lack of time and indistinct and/or inadequate financial compensation. Diagnostic and treatment patterns often differed from the outpatient clinic due to various patient-related and logistic factors. CONCLUSION: dermatologists are frequently confronted with nursing home patients but only a minority visits patients within nursing homes. Lack of time and/or financial compensation seem important barriers. PMID- 26552492 TI - Executive Dyscontrol of Learning and Memory: Findings from a Clade C HIV-positive South African Sample. AB - OBJECTIVE: Although pre-clinical work suggests there might be differences in neurovirulence across HIV-1 clades, few studies investigate neuropsychological deficits in the globally predominant clade C infection. The purpose of this study was to investigate verbal learning and memory performance in HIV-positive individuals in Cape Town, South Africa, where clade C is the most prevalent subtype of the virus. METHOD: Using a case-control design, we recruited 53 isiXhosa-speaking, cART-naive HIV-positive adults and 53 demographically matched HIV-negative controls. Participants were administered a comprehensive neuropsychological test battery. The test of interest was the Hopkins Verbal Learning Test-Revised (HVLT-R); previous studies have used that instrument to identify executive dyscontrol of verbal learning and memory processes in clade B HIV-positive participants. RESULTS: HIV-positive participants showed only partial impairment on the HVLT-R's learning/memory components (e.g., they recalled significantly fewer words across learning trials, but displayed relatively intact performance on delayed recall trials). They also displayed little executive dyscontrol over encoding and retrieval processes (e.g., there were no significant between-group differences on measures of semantic or serial clustering). CONCLUSIONS: Post-cART era studies suggest that verbal learning and memory performance is impaired in clade B samples, at least partially due to executive dyscontrol over encoding and retrieval processes. We found few such impairments in the current clade C sample. These preliminary findings suggest different CNS vulnerability across clades that would have implications for delineating clade specific neuropathological and neurocognitive clinical features. PMID- 26552493 TI - Infusing IVIG through Community Care Access Services in Patients with CIDP. PMID- 26552494 TI - Reference values for the volumes of foetal heart atrial wall by three-dimensional ultrasound using STIC and VOCAL methods between 20w0d and 33w6d weeks of gestation. AB - OBJECTIVE: To establish reference values for the volumes of foetal heart atrial wall by three-dimensional (3D) ultrasound using spatio-temporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL) methods. METHODS: We performed a retrospective cross-sectional study with 170 normal singleton pregnancies between 20 weeks + 0 days (20w0d) and 33 weeks + 6 days (33w6d) of gestation. Foetal heart atrial wall volume was obtained by VOCAL method with 30 degree rotation (six planes) subtracting the internal volume from the atrium volume. Polynomial regression with adjustments by determination coefficient (R(2)) was performed. To calculate the interobserver reproducibility, concordance correlation coefficient (CCC) was applied. RESULTS: The mean +/- standard deviation (SD) for the left atrium wall volume (cm(3)) ranged from 0.54 +/- 0.21 at 20w0d-20w6d to 2.17 +/- 0.30 at 33w0d-33w6d. The mean +/- SD for the right atrium wall volume (cm(3)) ranged from 0.45 +/- 0.16 at 20w0d-20w6d to 2.17 +/- 0.62 at 33w0d-33w6d. We observed a satisfactory interobserver reproducibility with CCC = 0.69 and 0.58 for the left and right volumes of foetal heart atrial wall, respectively. The best-fit models were first-degree: volume for the left atrium wall = -2.194 + 0.139*GA (R(2 )=( )0.41) and volume for the right atrium wall = -2.757 + 0.155*GA (R(2 )=( )0.37). CONCLUSION: Reference values for the volumes of foetal heart atrial wall by 3D ultrasound using STIC and VOCAL methods between 20w0d and 33w6d weeks of gestation were established. PMID- 26552495 TI - Mental health of sexual minorities. A systematic review. AB - Many studies, reviews, and meta-analyses have reported elevated mental health problems for sexual minority (SM) individuals. This systematic review provides an update by including numerous recent studies, and explores whether SM individuals are at increased risk across selected mental health problems as per dimensions of sexual orientation (SO), genders, life-stages, geographic regions, and in higher quality studies. A systematic search in PubMed produced 199 studies appropriate for review. A clear majority of studies reported elevated risks for depression, anxiety, suicide attempts or suicides, and substance-related problems for SM men and women, as adolescents or adults from many geographic regions, and with varied SO dimensions (behaviour, attraction, identity), especially in more recent and higher quality studies. One notable exception is alcohol-related problems, where many studies reported zero or reversed effects, especially for SM men. All SM subgroups were at increased risk, but bisexual individuals were at highest risk in the majority of studies. Other subgroup and gender differences are more complex and are discussed. The review supports the long-standing mental health risk proposition for SM individuals, overall and as subgroups. PMID- 26552496 TI - Inoculation methods using Rhodococcus erythropolis strain P30 affects bacterial assisted phytoextraction capacity of Nicotiana tabacum. AB - In this study different bacterial inoculation methods were tested for tobacco plants growing in a mine-soil contaminated with Pb, Zn, and Cd. The inoculation methods evaluated were: seed inoculation, soil inoculation, dual soil inoculation event, and seed+soil inoculation. Each inoculum was added at two bacterial densities (10(6) CFUs mL(-1) and 10(8) CFUs mL(-1)). The objectives were to evaluate whether or not the mode of inoculation or the number of applied microorganisms influences plant response. The most pronounced bacterial-induced effect was found for biomass production, and the soil inoculation treatment (using 10(6) CFUs mL(-1)) led to the highest increase in shoot dry weight yield (up to 45%). Bacterial-induced effects on shoot metal concentrations were less pronounced; although a positive effect was found on shoot Pb concentration when using 10(8) CFUs mL(-1) in the soil inoculation (29% increase) and in the seed+soil inoculation (34% increase). Also shoot Zn concentration increased by 24% after seed inoculation with 10(6) CFUs mL(-1). The best effects on the total metal yield were not correlated with an increasing number of inoculated bacteria. In fact the best results were found after a single soil inoculation using the lower cellular density of 10(6) CFUs mL(-1). PMID- 26552497 TI - JVIR Celebrates 25 Years of Innovation. Part 5: 2011-2015. PMID- 26552498 TI - Radioembolization following Liver Resection: Safety and Dosing Considerations. AB - PURPOSE: To evaluate the impact of previous liver resection on the safety of resin microsphere radioembolization (RE). MATERIALS AND METHODS: A single-center retrospective review was performed of 22 patients who underwent resin microsphere RE after liver resection during the period 2009-2014. Prescribed patient dose using the body surface area (BSA) model and a theoretical dose calculated from the actual liver volume on imaging were recorded. Patient and treatment characteristics were analyzed for factors that contributed to toxicity. RESULTS: In 13 patients, 20 grade 1-3 toxicities were identified. No differences in toxicity were seen based on extent of prior hepatic resection or whether whole liver treatments were performed (P = .2). The measured liver volume based on cross-sectional imaging correlated poorly with the expected liver volume based on BSA (r = 0.43). After adjusting for the patients' measured liver volume on cross sectional imaging, five patients were determined to be relatively overdosed and seven patients were determined to be relatively underdosed by the BSA method. Despite these differences, no association was found with patient toxicities and either an overestimation or an underestimation of liver volume (P = .4). CONCLUSION: Previous hepatic resection does not adversely alter the safety profile of yttrium-90 RE. BSA poorly predicts expected liver volume in this population. However, standard BSA-based dosing and whole-liver remnant treatments do not increase hepatotoxicity. PMID- 26552499 TI - Rational Molecular Engineering of Indoline-Based D-A-pi-A Organic Sensitizers for Long-Wavelength-Responsive Dye-Sensitized Solar Cells. AB - Indoline-based D-A-pi-A organic sensitizers are promising candidates for highly efficient and long-term stable dye-sensitized solar cells (DSSCs). In order to further broaden the spectral response of the known indoline dye WS-2, we rationally engineer the molecular structure through enhancing the electron donor and extending the pi-bridge, resulting in two novel indoline-based D-A-pi-A organic sensitizers WS-92 and WS-95. By replacing the 4-methylphenyl group on the indoline donor of WS-2 with a more electron-rich carbazole unit, the intramolecular charge transfer (ICT) absorption band of dye WS-92 is slightly red shifted from 550 nm (WS-2) to 554 nm (WS-92). In comparison, the incorporation of a larger pi-bridge of cyclopentadithiophene (CPDT) unit in dye WS-95 not only greatly bathochromatically tunes the absorption band to 574 nm but also largely enhances the molar extinction coefficients (epsilon), thus dramatically improving the light-harvesting capability. Under the standard global AM 1.5 solar light condition, the photovoltaic performances of both organic dyes have been evaluated in DSSCs on the basis of the iodide/triiodide electrolyte without any coadsorbent or cosensitizer. The DSSCs based on WS-95 display better device performance with power conversion efficiency (eta) of 7.69%. The additional coadsorbent in the dye bath of WS-95 does not improve the photovoltaic performance, indicative of its negligible dye aggregation, which can be rationalized by the grafted dioctyl chains on the CPDT unit. The cosensitization of WS-95 with a short absorption wavelength dye S2 enhances the IPCE and improves the eta to 9.18%. Our results indicate that extending the pi-spacer is more rational than enhancing the electron donor in terms of broadening the spectral response of indoline-based D-A pi-A organic sensitizers. PMID- 26552500 TI - Endoscopic management of bariatric surgery complications: what the gastroenterologist should know. AB - Obesity is a serious disorder in almost the entire world. It is an important risk factor for a series of conditions that affect and threaten health. Currently, bariatric surgery is the most effective treatment for morbid obesity, and in addition to the resulting weight loss, it reduces morbidity in this population. There has been a significant increase in the number of obese patients operated on. Despite the success of bariatric surgery, an important group of patients still present with major postoperative complications. In order for endoscopy to effectively contribute to the diagnosis and treatment of complications deriving from obesity surgery, the gastroenterologist must be aware of the particularities involved in bariatric surgery. The present article is a review of the resulting anatomic aspects of the main surgical techniques employed, the most common postoperative symptoms, the potential complications, and the possibilities that endoscopic diagnosis and treatment offer. Endoscopy is a growing and continuously evolving method in the treatment of bariatric surgery complications. The aim of this review is to contribute to the preparation of gastroenterologists so they can offer adequate endoscopic diagnosis and treatment to this high-risk population. PMID- 26552501 TI - The Efficacy of Movement Representation Techniques for Treatment of Limb Pain--A Systematic Review and Meta-Analysis. AB - Relatively new evidence suggests that movement representation techniques (ie, therapies that use the observation and/or imagination of normal pain-free movements, such as mirror therapy, motor imagery, or movement and/or action observation) might be effective in reduction of some types of limb pain. To summarize the evidence regarding the efficacy of those techniques, a systematic review with meta-analysis was performed. We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, AMED, PsychINFO, Physiotherapy Evidence Database, and OT-seeker up to August 2014 and hand-searched further relevant resources for randomized controlled trials that studied the efficacy of movement representation techniques in reduction of limb pain. The outcomes of interest were pain, disability, and quality of life. Study selection and data extraction were performed by 2 reviewers independently. We included 15 trials on the effects of mirror therapy, (graded) motor imagery, and action observation in patients with complex regional pain syndrome, phantom limb pain, poststroke pain, and nonpathological (acute) pain. Overall, movement representation techniques were found to be effective in reduction of pain (standardized mean difference [SMD] = -.82, 95% confidence interval [CI], -1.32 to -.31, P = .001) and disability (SMD = .72, 95% CI, .22-1.22, P = .004) and showed a positive but nonsignificant effect on quality of life (SMD = 2.61, 85% CI, -3.32 to 8.54, P = .39). Especially mirror therapy and graded motor imagery should be considered for the treatment of patients with complex regional pain syndrome. Furthermore, the results indicate that motor imagery could be considered as a potential effective treatment in patients with acute pain after trauma and surgery. To date, there is no evidence for a pain reducing effect of movement representation techniques in patients with phantom limb pain and poststroke pain other than complex regional pain syndrome. PERSPECTIVE: In this systematic review we synthesize the evidence for the efficacy of movement representation techniques (ie, motor imagery, mirror therapy, or action observation) for treatment of limb pain. Our findings suggest effective pain reduction in some types of limb pain. Further research should address specific questions on the optimal type and dose of therapy. PMID- 26552502 TI - Effects of Personal Exposure to Ambient Fine Particulate Matter on Acute Change in Nocturnal Heart Rate Variability in Subjects Without Overt Heart Disease. AB - The immediate effect within minutes to hours of personal exposure to ambient fine particulate matter (PM2.5) on cardiac autonomic function is limited, particularly at night. Our study aimed to assess the lagged association between personal exposure to PM2.5 and nocturnal heart rate variability. Repeated measures panel study among 21 community adults recruited from a local health clinic during the period of March 1, 2004, to August 31, 2004, in Boston, Massachusetts, in the United States. Ambulatory electrocardiogram and continuous monitoring of personal exposure to PM2.5 and were measured for up to 2 consecutive days. We calculated 5 minute time-specific average PM2.5 exposure for each participant. Mixed-effects models were fit for 5-minute SD of normal-to-normal intervals (SDNN) and 5-minute heart rate in relation to 5-minute PM2.5 exposure lagged in 5-minute intervals up to 4 hours. We found an 8.4% decrease in nocturnal SDNN (95% confidence interval [CI] -11.3% to -5.5%) and a 1.9% increase in nighttime heart rate (95% CI 1.1% to 2.7%) for an interquartile range increase in PM2.5 (13.6 MUg/m(3)), after adjusting for confounders. Significant decreases in nocturnal SDNN associated with PM2.5 exposure occurred within 2.5 hours. The largest decrease in nocturnal SDNN of -12.8% (95% CI -16.4 to -9.1%) that was associated with PM2.5 exposure was found with a lag of 25 minutes. Rapid changes in nocturnal heart rate variability associated with personal PM2.5 exposure occurred within the previous 2.5 hours, with the largest effects at 25 minutes, suggesting immediate cardiac autonomic effects of fine particulate exposure. PMID- 26552503 TI - Comparison of Ticagrelor Versus Thienopyridine Loading Effect on Fractional Flow Reserve in Patients With Coronary Artery Disease. AB - Ticagrelor loading dose (LD) increases adenosine plasma levels, which might interfere with fractional flow reserve (FFR) assessment because the latter is based on adenosine-induced hyperemia. In a prospective study, consecutive patients who underwent coronary angiography with at least 1 de novo stenosis >50% and <90% in severity amenable to intervention underwent FFR assessment using intravenous adenosine 140 MUg/kg/min for 3 minutes. Patients were subsequently randomized to either ticagrelor 180 mg (n = 38) or control thienopyridine (n = 38) (prasugrel 60 mg [n = 28] or clopidogrel 600 mg [n = 10]), followed by a second FFR assessment of the target lesion 2 hours after drug. Pre-drug, steady hyperemia FFR (sFFR, median, first to third quartiles) was 0.82 (0.75 to 0.88) and 0.81 (0.75 to 0.88), p = 0.9, whereas post-drug, 0.82 (0.72 to 0.87) and 0.79 (0.73 to 0.86), p = 0.5, in thienopyridine and ticagrelor-treated patients, respectively. The primary end point of percent relative change in sFFR between pre- and post-drug periods was greater in ticagrelor- than thienopyridine-treated patients, -1.24 (-5.54 to 0.0) versus -0.51 (-3.68 to 3.21), p = 0.03, respectively. Absolute change in sFFR between pre- and post-drug periods was marginally higher in ticagrelor- than thienopyridine-treated patients -0.01 ( 0.04 to 0.0) versus -0.005 (-0.03 to 0.02), p = 0.048, respectively. Reclassification of treatment decision at the sFFR <= 0.80 cutoff post-drug occurred in 6 (15.8%) versus 5 (13.2%) of ticagrelor- and thienopyridine-treated patients, respectively. In conclusion, after ticagrelor LD, an absolute and relative reduction in sFFR compared with thienopyridine LD is observed. Administration of ticagrelor should be considered as a potential source, albeit minor, of FFR variability. PMID- 26552504 TI - Racial Differences in Quality of Anticoagulation Therapy for Atrial Fibrillation (from the TREAT-AF Study). AB - The influence of race on quality of anticoagulation control is not well described. We examined the association between race, international normalized ratio (INR) monitoring intensity, and INR control in warfarin-treated patients with atrial fibrillation (AF). Using data from the Veterans Health Administration (VHA), we performed a retrospective cohort study of 184,161 patients with a new diagnosis of AF/flutter from 2004 to 2012 who received any VHA prescription within 90 days of diagnosis. The primary predictor was race, ascertained from multiple VHA and linked Medicare demographic files. The primary outcome was first year and long-term time in therapeutic range (TTR) of INR 2.0 to 3.0. Secondary outcomes were INR monitoring intensity and warfarin persistence. Of the 116,021 patients who received warfarin in the cohort, INR monitoring intensity was similar across racial groups. However, TTR was lowest in blacks and highest in whites (first year 0.49 +/- 0.23 vs 0.57 +/- 0.21, p <0.001; long term 0.52 +/- 0.20 vs 0.59 +/- 0.18, p <0.001); 64% of whites and 49% of blacks had long-term TTR >55% (p <0.001). After adjusting for site and patient-level covariates, black race was associated with lower first-year and long-term TTRs (4.2% and 4.1% below the conditional mean, relative to whites; p <0.0001 for both). One-year warfarin persistence was slightly lower in blacks compared to whites (58% vs 60%, p <0.0001). In conclusion, in patients with AF anticoagulated with warfarin, differences in INR control are most evident among blacks, underscoring the need to determine if other types of intensive management or warfarin alternatives may be necessary to improve anticoagulation among vulnerable AF populations. PMID- 26552505 TI - Diagnostic Performance of Cardiac Magnetic Resonance Imaging and Echocardiography in Evaluation of Cardiac and Paracardiac Masses. AB - Echocardiography is the preferred initial imaging method for assessment of cardiac masses. Cardiac magnetic resonance (CMR) imaging, with its excellent tissue characterization and wide field of view, may provide additional unique information. We evaluated the predictive value of echocardiography and CMR imaging parameters to identify tumors and malignancy and to provide histopathologic diagnosis of cardiac masses. Fifty patients who underwent CMR evaluation of a cardiac mass with subsequent histopathologic diagnosis were identified. Echocardiography was available in 44 of 50 cases (88%). Echocardiographic and CMR characteristics were evaluated for predictive value in distinguishing tumor versus nontumor and malignant versus nonmalignant lesions using histopathology as the gold standard. The Wilcoxon rank-sum test was used to compare the 2 imaging methods' ability to provide the correct histopathologic diagnosis. Parameters associated with tumor included location outside the right atrium, T2 hyperintensity, and contrast enhancement. Parameters associated with malignancy included location outside the cardiac chambers, nonmobility, pericardial effusion, myocardial invasion, and contrast enhancement. CMR identified 6 masses missed on transthoracic echocardiography (4 of which were outside the heart) and provided significantly more correct histopathologic diagnoses compared to echocardiography (77% vs 43%, p <0.0001). In conclusion, CMR offers the advantage of identifying paracardiac masses and providing crucial information on histopathology of cardiac masses. PMID- 26552506 TI - Cardiovascular Risk Assessment and Management in Prerenal Transplantation Candidates. AB - Cardiovascular (CV) assessment in prerenal transplant patients varies by center. Current guidelines recommend stress testing for candidates if >= 3 CV risk factors exist. We evaluated the CV assessment and management in 685 patients referred for kidney transplant over a 7-year period. All patients had CV risk factors, and the most common cause of end-stage renal disease was diabetes. Thirty-three percent (n = 229) underwent coronary angiography. The sensitivity of stress testing to detect obstructive coronary artery disease (CAD) was poor (0.26). Patients who had no CAD, nonobstructive CAD, or CAD with intervention had significantly higher event-free survival compared with patients with obstructive CAD without intervention. There were no adverse clinical events (death, myocardial infarction, stroke, revascularization, and graft failure) within 30 days post-transplant in patients who had preoperative angiography (n = 77). Of the transplanted patients who did not have an angiogram (n = 289), there were 8 clinical events (6 myocardial infarctions) in the first 30 days. In conclusion, our results indicate that stress testing and usual risk factors were poor predictors of obstructive CAD and that revascularization may prove beneficial in these patients. PMID- 26552508 TI - Cardiac Complications After Community-Acquired Pneumonia. PMID- 26552507 TI - Comparison of Efficacy and Safety of Left Atrial Appendage Occlusion in Patients Aged <75 to >= 75 Years. AB - Left atrial appendage occlusion (LAAO) is emerging as a promising alternative to oral anticoagulation. Because aged patients present a greater risk of not only cardioembolic events but also major bleeding, LAAO might represent a valid alternative as this would allow oral anticoagulation cessation while keeping cardioembolic protection. The objective of the study was to explore the safety and efficacy of LAAO in elderly patients. Data from the AMPLATZER Cardiac Plug multicenter registry were analyzed. The cohort was categorized in 2 groups (<75 vs >= 75 years). A total of 1,053 subjects were included in the registry. Of them, 219 were excluded because of combined procedures. As a result, 828 subjects were included (54.6% >= 75 years). Procedural success was high and similar in both groups (97.3%). Acute procedural major adverse events were not statistically different among groups (3.2% in <75 years vs 5.1%; p = 0.17) although stratified analysis showed a higher incidence of cardiac tamponade in elderly patients (0.5% vs 2.2%; p = 0.04). With a median follow-up of 16.8 months, no significant differences in stroke/TIA (1.9% vs 2.3%; p = 0.89) and major bleeding (1.7% vs 2.6%; p = 0.54) were observed. In conclusion, LAAO was associated with similar procedural success in patients aged <75 and >= 75 years although older patients had a higher incidence of cardiac tamponade. At follow-up, stroke and major bleeding rates were similar among groups. PMID- 26552509 TI - Cost-Effectiveness of Dabigatran (150 mg Twice Daily) and Warfarin in Patients >= 65 Years With Nonvalvular Atrial Fibrillation. AB - Dabigatran has been shown to be superior to warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) but with higher out-of-pocket costs for patients. Although dabigatran has been shown to be cost effective from a societal perspective, cost implications for individual patients and insurers are not well described. We aimed to assess cost perspectives of each payer (Medicare and patient) in relation to administration, monitoring, and adverse outcomes for dabigatran and warfarin in patients with and without prescription drug coverage. Using a Markov model, we performed a decision analysis comparing 2 treatment strategies (dose-adjusted warfarin and dabigatran 150 mg twice daily) in patients 65 years old with NVAF, CHADS2 scores >= 1, and Medicare insurance. Patients have a quality-adjusted life expectancy of 8.998 quality-adjusted life years with warfarin and 9.39 quality-adjusted life years with dabigatran 150 mg twice daily. From Medicare's perspective, the incremental cost-effectiveness ratio comparing dabigatran with warfarin was $35,311 for patients with Part D coverage and cost saving for patients without coverage. From the patient's perspective, the incremental cost-effectiveness ratio comparing dabigatran with warfarin was cost saving for patients with Part D coverage and $63,884 for those without coverage. In patients >= 65 years with NVAF and prescription insurance coverage, dabigatran 150 mg twice daily is both cost effective (Medicare's perspective) and cost saving (patient perspective) compared with warfarin, at a willingness-to-pay threshold of $100,000. However, patients without prescription drug coverage have a high out-of-pocket cost burden with dabigatran therapy, leading to a reduction in its cost-effectiveness compared with warfarin therapy. In conclusion, this Markov model suggests that Medicare Part D coverage influences the cost effectiveness of dabigatran 150 mg daily compared with dose-adjusted warfarin from multiple payer perspectives. PMID- 26552510 TI - Cost comparison of Transcatheter and Operative Pulmonary Valve Replacement (from the Pediatric Health Information Systems Database). AB - Outcomes for transcatheter pulmonary valve replacement (TC-PVR) and operative pulmonary valve replacement (S-PVR) are excellent. Thus, their respective cost is a relevant clinical outcome. We performed a retrospective cohort study of children and adults who underwent PVR at age >= 8 years from January 1, 2011, to December 31, 2013, at 35 centers contributing data to the Pediatric Health Information Systems database to address this question. A propensity score adjusted multivariable analysis was performed to adjust for known confounders. Secondary analyses of department-level charges, risk of re-admission, and associated costs were performed. A total of 2,108 PVR procedures were performed in 2,096 subjects (14% transcatheter and 86% operative). The observed cost of S PVR and TC-PVR was not significantly different (2013US $50,030 vs 2013US $51,297; p = 0.85). In multivariate analysis, total costs of S-PVR and TC-PVR were not significantly different (p = 0.52). Length of stay was shorter after TC-PVR (p <0.0001). Clinical and supply charges were greater for TC-PVR (p <0.0001), whereas laboratory, pharmacy, and other charges (all p <0.0001) were greater for S-PVR. Risks of both 7- and 30-day readmission were not significantly different. In conclusion, short-term costs of TC-PVR and S-PVR are not significantly different after adjustment. PMID- 26552511 TI - Usefulness of the Electrocardiographic P-Wave Axis as a Predictor of Atrial Fibrillation. AB - The association between abnormal electrocardiographic P-wave axis with atrial fibrillation (AF) has not been systematically studied in community-based populations. We examined the association between abnormal P-wave axis and AF in 4,274 participants (41% men and 95% white) from the Cardiovascular Health Study. Axis values between 0 degrees and 75 degrees were considered normal. AF cases were identified from study electrocardiograms and from hospitalization discharge data. During a median follow-up of 12.1 years, a total of 1,274 participants (30%) developed AF. The incidence rate of AF was 26 cases per 1,000 person-years for those with abnormal P-wave axis and 24 cases per 1,000 person-years for subjects with normal P-wave axis. Abnormal P-wave axis was associated with a 17% increased risk of AF (95% confidence interval 1.03 to 1.33) after adjustment for age, gender, race, education, income, smoking, diabetes, coronary heart disease, stroke, heart failure, heart rate, systolic blood pressure, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive medications, aspirin, and statins. The results were consistent in subgroup analyses stratified by age, gender, and race. In conclusion, abnormal P-wave axis, a routinely reported electrocardiographic measurement, is associated with an increased risk of AF. This finding suggests a potential role for P-wave axis in AF risk assessment. PMID- 26552512 TI - Prognosis of Low-Risk Young Women Presenting to the Emergency Department With Chest Pain. AB - Identification of patients at low risk presenting to the emergency department with chest pain is a continuing challenge. We examined a cohort of low-risk women with negative cardiac injury markers, electrocardiogram with normal results, and clinical stability. We hypothesized that these patients can be safely and accurately managed in a chest pain unit (CPU), may not require predischarge cardiac testing, and have an excellent short-term prognosis. The primary end point was major cardiovascular events during index admission or follow-up. Mean age of the 403 women was 42 +/- 4.3 years (30 to 50 years). No patient had a cardiovascular event in the CPU, and none of the 321 patients followed for 6 months had a late cardiovascular event. Most (211, 52%) did not receive predischarge cardiac testing. The remaining 192 patients (48%) had predischarge exercise treadmill test, stress imaging, or cardiac catheterization. Of those patients who underwent treadmill testing, almost 90% had no exercise-induced chest pain and approximately 50% had functional capacity 8 to 14 METs. In addition, 166 patients (41%) were discharged from the CPU after <2 hours and 21% (n = 86) within 2 to 8 hours. In conclusion, this group of low-risk women was safely and accurately managed in the CPU and discharged promptly. There were no cardiac events on index admission or 6-month follow-up, and in most patients, predischarge cardiac testing was unnecessary. PMID- 26552513 TI - Group Beating in a Woman With a DDD Pacemaker. PMID- 26552514 TI - A Cold Limit to Adaptation in the Sea. AB - Temperature affects biological functions by altering reaction rates. Physiological rates usually double to treble for every 10 degrees C rise, and 1 4 fold encompasses normal biological functions. However, in polar marine species inhabiting temperatures around 0 degrees C many processes are slowed beyond the Arrhenius relationships for warmer water species. Growth, embryonic development, Specific dynamic action (SDA) duration, and time to acclimate to altered temperature, are all 5-12 fold slower in species living near 0 degrees C than at 10 degrees C. This cold marine physiological transition to slower states is absent, however, in oxygen consumption and SDA factorial scope; processes where capacity is related to aerobic scope. My opinion is that processes involving significant protein modification are impacted, and protein synthesis or folding problems cause the slowing of rates beyond expected temperature effects. PMID- 26552515 TI - Leadership in Mammalian Societies: Emergence, Distribution, Power, and Payoff. AB - Leadership is an active area of research in both the biological and social sciences. This review provides a transdisciplinary synthesis of biological and social-science views of leadership from an evolutionary perspective, and examines patterns of leadership in a set of small-scale human and non-human mammalian societies. We review empirical and theoretical work on leadership in four domains: movement, food acquisition, within-group conflict mediation, and between group interactions. We categorize patterns of variation in leadership in five dimensions: distribution (across individuals), emergence (achieved versus inherited), power, relative payoff to leadership, and generality (across domains). We find that human leadership exhibits commonalities with and differences from the broader mammalian pattern, raising interesting theoretical and empirical issues. PMID- 26552516 TI - Measurement of human CYP1A2 induction by inhalation exposure to benzo(a)pyrene based on in vivo isotope breath method. AB - Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as 'exposure' group, and non-smoking healthy office workers in the same city (n = 10) were selected as 'control' group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group (p < 0.001). However, the exposure group did not exhale significant higher levels of (13)CO2/(12)CO2 in breath samples (p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the (13)CO2/(12)CO2 ratio (p = 0.91). A significant association was found between the (13)CO2/(12)CO2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP. PMID- 26552517 TI - Reliable low-cost devices for monitoring ammonia concentrations and emissions in naturally ventilated dairy barns. AB - This research investigated the use of two relatively cost-effective devices for determining NH3 concentrations in naturally ventilated (NV) dairy barns including an Ogawa passive sampler (Ogawa) and a passive flux sampler (PFS). These samplers were deployed adjacent to sampling ports of a photoacoustic infrared multigas spectroscope (INNOVA), in a NV dairy barn. A 3-day deployment period was deemed suitable for both passive samplers. The correlations between concentrations determined with the passive samplers and the INNOVA were statistically significant (r = 0.93 for Ogawa and 0.88 for PFS). Compared with reference measurements, Ogawa overestimated NH3 concentrations in the barn by ~ 14%, while PFS underestimated NH3 concentrations by ~ 41%. Barn NH3 emission factors per animal unit (20.6-21.2 g d(-1) AU(-1)) based on the two passive samplers, after calibration, were similar to those obtained with the reference method and were within the range of values reported in literature. PMID- 26552518 TI - The impacts of surface ozone pollution on winter wheat productivity in China--An econometric approach. AB - The impact of surface ozone pollution on winter wheat yield is empirically estimated by considering socio-economic and weather determinants. This research is the first to use an economic framework to estimate the ozone impact, and a unique county-level panel is employed to examine the impact of the increasing surface ozone concentration on the productivity of winter wheat in China. In general, the increment of surface ozone concentration during the ozone-sensitive period of winter wheat is determined to be harmful to its yield, and a conservative reduction of ozone pollution could significantly increase China's wheat supply. PMID- 26552519 TI - Effects of conventional and biodegradable microplastics on a marine ecosystem engineer (Arenicola marina) and sediment nutrient cycling. AB - Effects of microplastic pollution on benthic organisms and ecosystem services provided by sedimentary habitats are largely unknown. An outdoor mesocosm experiment was done to realistically assess the effects of three different types of microplastic pollution (one biodegradable type; polylactic acid and two conventional types; polyethylene and polyvinylchloride) at increasing concentrations (0.02, 0.2 and 2% of wet sediment weight) on the health and biological activity of lugworms, Arenicola marina (Linnaeus, 1758), and on nitrogen cycling and primary productivity of the sediment they inhabit. After 31 days, A. marina produced less casts in sediments containing microplastics. Metabolic rates of A. marina increased, while microalgal biomass decreased at high concentrations, compared to sediments with low concentrations or without microplastics. Responses were strongest to polyvinylchloride, emphasising that different materials may have differential effects. Each material needs to be carefully evaluated in order to assess their risks as microplastic pollution. Overall, both conventional and biodegradable microplastics in sandy sediments can affect the health and behaviour of lugworms and directly or indirectly reduce primary productivity of these habitats. PMID- 26552520 TI - Impacts of explosive compounds on vegetation: A need for community scale investigations. AB - Explosive compounds are distributed heterogeneously across the globe as a result of over a century of human industrial and military activity. RDX (hexahydro-1,3,5 trinitro-1,3,5-triazine) and TNT (2-methyl-1,3,5-trinitrobenzene) are the most common and most abundant explosives in the environment. Vegetation exhibits numerous physiological and morphological stress responses in the presence of RDX and TNT. Varied stress responses act as physiological filters that facilitate the proliferation of tolerant species and the extirpation of intolerant species. Contaminants alter community composition as they differentially impact plants at each life stage (i.e. germination, juvenile, adult), subsequently modifying larger scale ecosystem processes. This review summarizes the current explosives vegetation literature, focusing on RDX and TNT as these are well documented in the literature, linking our current understanding to ecological theory. A conceptual framework is provided that will aid future efforts in predicting plant community response to residual explosive compounds. PMID- 26552521 TI - Determination of moderately polar arsenolipids and mercury speciation in freshwater fish of the River Elbe (Saxony, Germany). AB - Arsenic and mercury are frequent contaminants in the environment and care must be taken to limit their entrance into the food chain. The toxicity of both elements strongly depends upon their speciation. Total amounts of As and Hg as well as their species were analyzed in muscle and liver of 26 fishes of seven freshwater fish species caught in the River Elbe. The median concentrations of As were 162 MUg kg(-1) w.w. in liver and 92 MUg kg(-1) w.w. in muscle. The median concentrations of total Hg were 241 MUg kg(-1) w.w. in liver and 256 MUg kg(-1) w.w. in muscle. While this level of Hg contamination of the freshwater fish in the River Elbe is significantly lower than 20 years ago, it exceeds the recommended environmental quality standard of 20 MUg Hg kg(-1) w.w. by a factor of 5-50. However, the European maximum level of 500 MUg Hg kg(-1) for fish for human consumption is rarely exceeded. Arsenic-containing fatty acids and hydrocarbons were determined and partially identified in methanolic extracts of the fish by HPLC coupled in parallel to ICP-MS (element specific detection) and ESI-Q-TOF-MS (molecular structure detection). While arsenobetaine was the dominant As species in the fish, six arsenolipids were detected and identified in the extracts of liver tissue in common bream (Abramis brama), ide (Leuciscus idus), asp (Aspius aspius) and northern pike (Esox lucius). Four arsenic containing fatty acids (AsFA) and two arsenic-containing hydrocarbons (AsHC) are reported in freshwater fish for the first time. With respect to mercury the more toxic MeHg(+) was the major species in muscle tissue (>90% of total Hg) while in liver Hg(2+) and MeHg(+) were of equal importance. The results show the high relevance of element speciation in addition to the determination of total element concentrations to correctly assess the burden of these two elements in fish. PMID- 26552522 TI - Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus). AB - Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. PMID- 26552523 TI - Size evolution of ultrafine particles: Differential signatures of normal and episodic events. AB - The effect of fireworks on the aerosol number characteristics of atmosphere was studied for an urban mega city. Measurements were made at 50 m height to assess the local changes around the festival days. Apart from the increase in total number concentration and characteristic accumulation mode, short-term increase of ultrafine particle concentration was noted. Total number concentration varies an order of magnitude during the measurement period in which peak occurs at a frequency of approximately one per day. On integral scale, it seems not possible to distinguish an episodic (e.g. firework bursting induced aerosol emission) and a normal (ambient atmospheric changes) event. However these events could be differentiated on the basis of size evolution analysis around number concentration peaks. The results are discussed relative to past studies and inferences are drawn towards aerosol signatures of firework bursting. The short term burst in ultrafine particle concentration can pose an inhalation hazard. PMID- 26552524 TI - Assessment of polycyclic aromatic hydrocarbons in indoor and outdoor air of preschool environments (3-5 years old children). AB - This work characterizes levels of polycyclic aromatic hydrocarbons (PAHs) in indoor and outdoor air of preschool environments, and assesses the respective risks for 3-5-years old children. Eighteen gaseous and particulate (PM1 and PM2.5) PAHs were collected indoors and outdoors during 63 days at preschools in Portugal. Gaseous PAHs accounted for 94-98% of total concentration (SigmaPAHs). PAHs with 5-6 rings were predominantly found in PM1 (54-74% particulate SigmaPAHs). Lighter PAHs originated mainly from indoor sources whereas congeners with 4-6 rings resulted mostly from outdoor emissions penetration (motor vehicle, fuel burning). Total cancer risks of children were negligible according to USEPA, but exceeded (8-13 times) WHO health-based guideline. Carcinogenic risks due to indoor exposure were higher than for outdoors (4-18 times). PMID- 26552525 TI - Effect of chemical stress and ultraviolet radiation in the bacterial communities of zebrafish embryos. AB - This study aimed to assess the effect of ultraviolet radiation (UVR) and chemical stress (triclosan-TCS; potassium dichromate-PD; prochloraz-PCZ) on bacterial communities of zebrafish (Danio rerio) embryos (ZEBC). Embryos were exposed to two UVR intensities and two chemical concentrations not causing mortality or any developmental effect (equivalent to the No-Observed-Effect Concentration-NOEC; NOEC diluted by 10-NOEC/10). Effects on ZEBC were evaluated using denaturing gradient gel electrophoresis (DGGE) and interpreted considering structure, richness and diversity. ZEBC were affected by both stressors even at concentrations/doses not affecting the host-organism (survival/development). Yet, some stress-tolerant bacterial groups were revealed. The structure of the ZEBC was always affected, mainly due to xenobiotic presence. Richness and diversity decreased after exposure to NOEC of PD. Interactive effects occurred for TCS and UVR. Aquatic microbiota imbalance might have repercussions for the host/aquatic system, particularly in a realistic scenario/climate change perspective therefore, future ecotoxicological models should consider xenobiotics interactions with UVR. PMID- 26552526 TI - Physicochemical factors affecting the spatial variance of monomethylmercury in artificial reservoirs. AB - The aim of this study was to identify how hydrologic factors (e.g., rainfall, maximum depth, reservoir and catchment area, and water residence time) and water chemistry factors (e.g., conductivity, pH, suspended particulate matter, chlorophyll-a, dissolved organic carbon, and sulfate) interact to affect the spatial variance in monomethylmercury (MMHg) concentration in nine artificial reservoirs. We hypothesized that the MMHg concentration of reservoir water would be higher in eutrophic than in oligotrophic reservoirs because increased dissolved organic matter and sulfate in eutrophic reservoirs can promote in situ production of MMHg. Multiple tools, including Pearson correlation, a self organizing map, and principal component analysis, were applied in the statistical modeling of Hg species. The results showed that rainfall amount and hydraulic residence time best explained the variance of dissolved Hg and dissolved MMHg in reservoir water. High precipitation events and residence time may mobilize Hg and MMHg in the catchment and reservoir sediment, respectively. On the contrary, algal biomass was a key predictor of the variance of the percentage fraction of unfiltered MMHg over unfiltered Hg (%MMHg). The creation of suboxic conditions and the supply of sulfate subsequent to the algal decomposition seemed to support enhanced %MMHg in the bloom reservoirs. Thus, the nutrient supply should be carefully managed to limit increases in the %MMHg/Hg of temperate reservoirs. PMID- 26552527 TI - Seasonal and spatial variations of PPCP occurrence, removal and mass loading in three wastewater treatment plants located in different urbanization areas in Xiamen, China. AB - The occurrence and fate of 48 pharmaceuticals and personal care products (PPCPs) in three wastewater treatment plants (WWTPs) located in different urbanization areas in Xiamen, China was investigated over one year. Results showed that PPCPs were widely detected, but the major PPCPs in the influent, effluent, and sludge were different. Spatial and seasonal variations of PPCP levels in the influent and sludge were observed. The removal efficiencies for most PPCPs were similar among the three WWTPs, although they employed different biological treatment processes. Furthermore, the mass loadings per inhabitant of most pharmaceuticals had a positive correlation with the urbanization levels, indicating that most pharmaceutical usage was higher in the urban core compared to the suburban zones. The total mass loadings of all the 48 PPCPs in the effluent and waste sludge showed close proportions, which suggested the importance of proper waste sludge disposal to prevent a large quantity of PPCPs from entering the environment. PMID- 26552528 TI - Short-term exposure to benzo[a]pyrene causes oxidative damage and affects haemolymph steroid levels in female crab Portunus trituberculatus. AB - Concern has increased regarding the adverse effects of polycyclic aromatic hydrocarbons (PAHs) on reproduction. However, limited information is available on the effects of PAHs in crustacean. In order to determine whether benzo[a]pyrene (B[a]P) could cause reproductive toxicity on the swimming crab Portunus trituberculatus, sexually mature female crabs were exposed to environmentally relevant concentrations of B[a]P (0, 0.1, 0.5 and 2.5 MUg/L) for 10 days. B[a]P treatments resulted in high accumulation in ovary, and induced oxidative stress in a dose-dependent manner on ovary of crab. Furthermore, the haemolymph estradiol (E2) and testosterone (T) levels were significantly decreased. Histological investigation also revealed the reproductive toxicity caused by B[a]P. The results demonstrated that waterborne exposure to B[a]P caused oxidative damage and disrupted sex steroids in female crab P. trituberculatus, ultimately resulting in histological alternation. PMID- 26552529 TI - Reproduction impairment and endocrine disruption in female zebrafish after long term exposure to MC-LR: A life cycle assessment. AB - Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 MUg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHbeta and LHbeta along with ovarian ERalpha, FSHR and LHR suggested positive feedback regulation in the HPGL axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERalpha and VTG1 expression were all down regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs contaminated aquatic environment. PMID- 26552530 TI - An evaluation of the toxicity and bioaccumulation of bismuth in the coastal environment using three species of macroalga. AB - Bismuth is a heavy metal whose biogeochemical behaviour in the marine environment is poorly defined. In this study, we exposed three different species of macroalga (the chlorophyte, Ulva lactuca, the phaeophyte, Fucus vesiculosus, and the rhodophyte, Chondrus crispus) to different concentrations of Bi (up to 50 MUg L( 1)) under controlled, laboratory conditions. After a period of 48-h, the phytotoxicity of Bi was measured in terms of chlorophyll fluorescence quenching, and adsorption and internalisation of Bi determined by ICP after EDTA extraction and acid digestion, respectively. For all algae, both the internalisation and total accumulation of Bi were proportional to the concentration of aqueous metal. Total accumulation followed the order: F. vesiculosus > C. crispus > U. lactuca; with respective accumulation factors of about 4200, 1700 and 600 L kg(-1). Greatest internalisation (about 33% of total accumulated Bi) was exhibited by C. crispus, the only macroalga to display a phytotoxic response in the exposures. A comparison of the present results with those reported in the literature suggests that Bi accumulation by macroalgae is significantly lower than its accumulation by marine plankton (volume concentration factors of 10(5) to 10(7)), and that the phytotoxicity of Bi is low relative to other heavy metals like Ag and Tl. PMID- 26552531 TI - Effects of soil texture and drought stress on the uptake of antibiotics and the internalization of Salmonella in lettuce following wastewater irrigation. AB - Treated wastewater is expected to be increasingly used as an alternative source of irrigation water in areas facing fresh water scarcity. Understanding the behaviors of contaminants from wastewater in soil and plants following irrigation is critical to assess and manage the risks associated with wastewater irrigation. The objective of this study was to evaluate the effects of soil texture and drought stress on the uptake of antibiotics and the internalization of human pathogens into lettuce through root uptake following wastewater irrigation. Lettuce grown in three soils with variability in soil texture (loam, sandy loam, and sand) and under different levels of water stress (no drought control, mild drought, and severe drought) were irrigated with synthetic wastewater containing three antibiotics (sulfamethoxazole, lincomycin and oxytetracycline) and one Salmonella strain a single time prior to harvest. Antibiotic uptake in lettuce was compound-specific and generally low. Only sulfamethoxazole was detected in lettuce with increasing uptake corresponding to increasing sand content in soil. Increased drought stress resulted in increased uptake of lincomycin and decreased uptake of oxytetracycline and sulfamethoxazole. The internalization of Salmonella was highly dependent on the concentration of the pathogen in irrigation water. Irrigation water containing 5 Log CFU/mL Salmonella resulted in limited incidence of internalization. When irrigation water contained 8 Log CFU/mL Salmonella, the internalization frequency was significantly higher in lettuce grown in sand than in loam (p = 0.009), and was significantly higher in lettuce exposed to severe drought than in unstressed lettuce (p = 0.049). This work demonstrated how environmental factors affected the risk of contaminant uptake by food crops following wastewater irrigation. PMID- 26552533 TI - Occurrence and sources of natural and anthropogenic lipid tracers in surface soils from arid urban areas of Saudi Arabia. AB - Soil particles contain a variety of natural and anthropogenic organic components, and in urban areas can be considered as local collectors of pollutants. Surface soil samples were taken from ten urban areas in Riyadh during early winter of 2007. They were extracted with dichloromethane-methanol mixture and the extracts were analyzed by gas chromatography-mass spectrometry. The major compounds were unresolved complex mixture (UCM), plasticizers, n-alkanes, carbohydrates, n alkanoic acids, hopanes, n-alkanols, and sterols. Vegetation detritus was the major natural source of organic compounds (24.0 +/- 15.7%) in samples from areas with less human activities and included n-alkanes, n-alkanoic acids, n-alkanols, sterols and carbohydrates. Vehicular emission products and discarded plastics were the major anthropogenic sources in the soil particles (53.3 +/- 21.3% and 22.7 +/- 10.7%, respectively). The anthropogenic tracers were UCM, plasticizers, n-alkanes, hopanes and traces of steranes. Vegetation and human activities control the occurrence and distribution of natural and anthropogenic extractable organic matter in this arid urban area. PMID- 26552532 TI - Phytotoxicity of wastewater-born micropollutants--Characterisation of three antimycotics and a cationic surfactant. AB - Sewage sludge applied to soil may be a valuable fertiliser but can also introduce poorly degradable and highly adsorptive wastewater-born residues of pharmaceuticals and personal care products (PPCPs) to the soil, posing a potential risk to the receiving environment. Three azole antimycotics (climbazole, ketoconazole and fluconazole), and one quaternary ammonium compound (benzyldimethyldodecylammonium chloride, BDDA) that are frequently detected in municipal sewage sludge and/or treated wastewater were therefore characterised in their toxicity toward terrestrial (Brassica napus) and aquatic (Lemna minor) plants. Fluconazole and climbazole showed the greatest toxicity to B. napus, while toxicity of ketoconazole and BDDA was by one to two orders of magnitude lower. Sludge amendment to soil at an agriculturally realistic rate of 5 t/ha significantly reduced the bioconcentration of BDDA in B. napus shoots compared to tests without sludge amendment, although not significantly reducing phytotoxicity. Ketoconazole, fluconazole and BDDA proved to be very toxic to L. minor with median effective concentrations ranging from 55.7 MUg/L to 969 MUg/L. In aquatic as well as terrestrial plants, the investigated azoles exhibited growth-retarding symptoms presumably related to an interference with phytohormone synthesis as known for structurally similar fungicides used in agriculture. While all four substances exhibited considerable phytotoxicity, the effective concentrations were at least one order of magnitude higher than concentrations measured in sewage sludge and effluent. Based on preliminary hazard quotients, BDDA and climbazole appeared to be of greater environmental concern than the two pharmaceuticals fluconazole and ketoconazole. PMID- 26552534 TI - Assessment of biological effects of environmental pollution in Mersin Bay (Turkey, northeastern Mediterranean Sea) using Mullus barbatus and Liza ramada as target organisms. AB - The increasing emphasis on the assessment and monitoring of marine ecosystems has revealed the need to use appropriate biological indicators for these areas. Enzyme activities and histopathology are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of pollutant exposure. As part of an ecotoxicological assessment of Mersin Bay, EROD enzyme activity and histopathological response in selected organs and tissues of two species of fish, Mullus barbatus (red mullet) and Liza ramada (thinlip grey mullet), captured from area were examined. Pollutant (Organochlorines (OC), alkylphenols (APs) and BPA) levels and biomarker responses in tissue samples were evaluated together for their potential to alter the metabolism and cellular aspects in liver and gonad. Elevated induction of EROD activity and histopathological alterations in contaminated samples from Mersin Bay was observed compared to reference site indicating the exposure to potential pollutants. PMID- 26552535 TI - Fractionation of airborne particulate-bound elements in haze-fog episode and associated health risks in a megacity of southeast China. AB - Haze caused by high particulate matter loadings is an important environmental issue. PM2.5 was collected in Nanjing, China, during a severe haze-fog event and clear periods. The particulate-bound elements were chemically fractionated using sequential extractions. The average PM2.5 concentration was 3.4 times higher during haze-fog (96-518 MUg/m(3)) than non-haze fog periods (49-142 MUg/m(3)). Nearly all elements showed significantly higher concentrations during haze-fog than non-haze fog periods. Zn, As, Pb, Cd, Mo and Cu were considered to have higher bioavailability and enrichment degree in the atmosphere. Highly bioavailable fractions of elements were associated with high temperatures. The integrated carcinogenic risk for two possible scenarios to individuals exposed to metals was higher than the accepted criterion of 10(-6), whereas noncarcinogenic risk was lower than the safe level of 1. Residents of a city burdened with haze will incur health risks caused by exposure to airborne metals. PMID- 26552536 TI - Feeding reduces waterborne Cu bioaccumulation in a marine rabbitfish Siganus oramin. AB - Waterborne metal uptake has been extensively studied and dietary metal assimilation is increasingly recognized in fish, whilst the interaction between the two uptake routes is largely overlooked. This study compared the waterborne Cu bioaccumulation ((65)Cu as tracer) in a juvenile rabbitfish at different feeding regimes (starvation (SG), feeding normal diet (NDG) or diet supplemented with extra Cu (DCG)) to test the hypothesis that feeding can influence waterborne metal uptake in marine fish. NDG and DCG diet was fed as a single meal and then all fish were exposed to waterborne (65)Cu for 48 h, during which the time course sampling was conducted to determine (65)Cu bioaccumulation, chyme flow and dietary Cu assimilation. The results revealed that SG fish accumulated the highest (65)Cu, followed by NDG (61% of SG), whilst DCG fish accumulated the lowest (65)Cu (34% of SG). These results suggested a protective effect of feeding against waterborne Cu bioaccumulation. This effect was most notable between 10 min and 16 h when there was chyme in gastrointestinal tract (GT). Dietary Cu assimilation mainly occurred before 16 h after feeding. Waterborne (65)Cu influx rate in the GT was positively correlated with (65)Cu contents of chyme in NDG, whereas it was largely negatively correlated with (65)Cu contents of chyme in DCG. The waterborne Cu uptake in the GT was mainly influenced by the chyme flow and dietary Cu assimilation. Overall, our findings suggested that feeding has an important effect on waterborne metal uptake and that both the feeding status of the fish and the relative metal exposure through water and food should be considered in prediction of the metal bioaccumulation and biomonitoring programs. PMID- 26552537 TI - Isoprenoids emission in Stipa tenacissima L.: Photosynthetic control and the effect of UV light. AB - Fluxes of CO2 and isoprenoids were measured for the first time in Stipa tenacissima L (alfa grass), a perennial tussock grass dominant in the driest areas of Europe. In addition, we studied how those fluxes were influenced by environmental conditions, leaf ontogeny and UV radiation and compared emission rates in two contrasting seasons: summer when plants are mostly inactive and autumn, the growing season in this region. Leaf ontogeny significantly affected both photosynthesis and isoprenoids emission. Isoprene emission was positively correlated with photosynthesis, although a low isoprene emission was detected in brown leaves with a net carbon loss. Moreover, leaves with a significant lower photosynthesis emitted only monoterpenes, while at higher photosynthetic rates also isoprene was produced. Ambient UV radiation uncoupled photosynthesis and isoprene emission. It is speculated that alfa grass represent an exception from the general rules governing plant isoprenoid emitters. PMID- 26552538 TI - Distributions and compositions of old and emerging flame retardants in the rhizosphere and non-rhizosphere soil in an e-waste contaminated area of South China. AB - We investigated rhizosphere effects on the distributions and compositions of polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), and dechlorane plus (DPs) in rhizosphere soils (RS) and non-rhizosphere soils (NRS) in an e-waste recycling area in South China. The concentrations of PBDEs, NBFRs, and DPs ranged from 13.9 to 351, 11.6 to 70.8, and 0.64 to 8.74 ng g(-1) in RS and 7.56 to 127, 8.98 to 144, and 0.38 to 8.45 ng g(-1) in NRS, respectively. BDE-209 and DBDPE were the dominant congeners of PBDEs and NBFRs, respectively. PBDEs, NBFRs, and DPs were more enriched in RS than NRS in most vegetables species. Further analysis suggested that the differentiation of the rhizosphere effect on halogenated flame retardants (HFRs) was not solely controlled by the octanol-water coefficients. This difference was also reflected by the correlations between total organic carbon (TOC) and PBDEs, NBFRs, or DPs, which indicated that organic carbon was a more pivotal controlling factor for PBDEs and DPs than for NBFRs in soil. We also found significant positive correlations between PBDEs and their replacement products, which indicated a similar emission pattern and environmental behaviour. PMID- 26552539 TI - Association between air pollution and sperm quality: A systematic review and meta analysis. AB - Exposure to ambient air pollution has been clearly linked to adverse reproductive outcome and fecundation index, but its effects on male semen quality are still uncertain. In this study, we reviewed information from ten studies to get the qualitative evidence of the influence of the ambient air pollution on sperm quality and collected data from six of the ten studies to conduct meta-analysis. The original studies classified participants into different exposure levels and the highest and lowest expose levels were chosen as high expose and low expose groups, respectively. The random-effect model was used in the meta-analysis with the weight mean difference (WMD) as the measure indicator. The WMDs (95% confidence intervals, CIs) of sperm volume, sperm count, semen concentration, sperm progressive motility, total motility, and normal morphology were 0.09 ( 0.04, 0.23), 0.46 (-4.47, 5.39), -8.21 (-20.38, 3.96), -7.76 (-16.26, 0.74), 7.61 (-16.97, 1.74) and -3.40 (-7.42, 0.62), respectively. In conclusion, although the differences are not statistically significant between the two groups, the overall trends and evidence from this review indicate the chronic exposure to ambient pollutants at high level may alter men sperm quality. PMID- 26552540 TI - Identification and characterization of tebuconazole transformation products in soil by combining suspect screening and molecular typology. AB - Pesticides generate transformation products (TPs) when they are released into the environment. These TPs may be of ecotoxicological importance. Past studies have demonstrated how difficult it is to predict the occurrence of pesticide TPs and their environmental risk. The monitoring approaches mostly used in current regulatory frameworks target only known ecotoxicologically relevant TPs. Here, we present a novel combined approach which identifies and categorizes known and unknown pesticide TPs in soil by combining suspect screening time-of-flight mass spectrometry with in silico molecular typology. We used an empirical and theoretical pesticide TP library for compound identification by both non-target and target time-of-flight (tandem) mass spectrometry, followed by structural proposition through a molecular structure correlation program. In silico molecular typology was then used to group TPs according to common molecular descriptors and to indirectly elucidate their environmental parameters by analogy to known pesticide compounds with similar molecular descriptors. This approach was evaluated via the identification of TPs of the triazole fungicide tebuconazole occurring in soil during a field dissipation study. Overall, 22 empirical and 12 yet unknown TPs were detected, and categorized into three groups with defined environmental properties. This approach combining suspect screening time-of-flight mass spectrometry with molecular typology could be extended to other organic pollutants and used to rationalize the choice of TPs to be investigated towards a more comprehensive environmental risk assessment scheme. PMID- 26552541 TI - PCB and PBDE levels in a highly threatened dolphin species from the Southeastern Brazilian coast. AB - In the Northern coast of Rio de Janeiro State is located the major urban centers of the oil and gas industry of Brazil. The intense urbanization in recent decades caused an increase in human use of the coastal areas, which is constantly impacted by agricultural, industrial and wastewater discharges. Franciscana dolphin (Pontoporia blainvillei) is a small cetacean that inhabits coastal regions down to a 30 m depth. This species is considered the most threatened cetacean in the Western South Atlantic Ocean. This study investigated the levels of 52 PCB congeners and 9 PBDE congeners in liver of nine individuals found stranded or accidentally caught between 2011 and 2012 in the Northern coast of Rio de Janeiro. PCB mean levels ranged from 208 to 5543 ng g(-1) lw and PBDEs mean concentrations varied between 13.84 and 36.94 ng g(-1) lw. Contamination patterns suggest the previous use of Aroclor 1254, 1260 and penta-BDE mixtures in Brazil. While still few studies have assessed the organic contamination in cetaceans from the Southern Hemisphere, including Brazil, the levels found in this study could represent a health risk to these endangered species. PMID- 26552542 TI - Site energy distribution analysis of Cu (II) adsorption on sediments and residues by sequential extraction method. AB - Many models (e.g., Langmuir model, Freundlich model and surface complexation model) have been successfully used to explain the mechanism of metal ion adsorption on the pure mineral materials. These materials usually have a homogeneous surface where all sites have the same adsorption energies. However, it's hardly appropriate for such models to describe the adsorption on heterogeneous surfaces (e.g., sediment surface), site energy distribution analysis can be to. In the present study, the site energy distribution analysis was used to describe the surface properties and adsorption behavior of the non residual and residual components extracted from the natural aquatic sediment samples. The residues were prepared "in-situ" by using the sequential extraction procedure. The present study is intended to investigate the roles of different components and the change of site energy distribution at different temperatures of the sediment samples in controlling Cu (II) adsorption. The results of the site energy distribution analysis indicated firstly, that the sorption sites of iron/manganese hydrous oxides (IMHO) and organic matter (OM) have higher energy. Secondly, light fraction (LF) and carbonates have little influence on site energy distribution. Finally, there was increase in site energies with the increase of temperature. Specially, low temperature (5 degrees C) significantly influenced the site energies of IMHO and OM, and also had obvious effect on the energy distribution of the sediments after removing target components. The site energy distribution analysis proved to be a useful method for us to further understand the energetic characteristics of sediment in comparison with those previously obtained. PMID- 26552543 TI - Silver nanoparticles impact the functional role of Gammarus roeseli (Crustacea Amphipoda). AB - Silver nanoparticles (nAg) are widely used in consumer products and the risk associated with their potential release into freshwater ecosystems needs to be addressed using environmentally realistic exposure concentrations. Here, the effects of low concentrations (0.5-5 MUg L(-1)) of two different sized nAg (10 and 60 nm) and a silver nitrate positive control were evaluated in Gammarus roeseli following exposure for 72 h. Cellular, individual and functional endpoints were independently studied and the most striking results were reported for functional endpoints. Indeed, without a change in their feeding activity, the gammarids produced significantly fewer fine particles of organic matter when exposed to nAg, even at 0.5 MUg L(-1) of 10 nm nAg. These functional endpoints seem to be efficient markers for detecting the early effects of nAg on G. roeseli. PMID- 26552544 TI - Nickel toxicity to benthic organisms: The role of dissolved organic carbon, suspended solids, and route of exposure. AB - Nickel bioavailability is reduced in the presence of dissolved organic carbon (DOC), suspended solids (TSS), and other complexing ligands; however, no studies have examined the relative importance of Ni exposure through different compartments (water, sediment, food). Hyalella azteca and Lymnaea stagnalis were exposed to Ni-amended water, sediment, and food, either separately or in combination. Both organisms experienced survival and growth effects in several Ni compartment tests. The DOC amendments attenuated L. stagnalis Ni effects (survival, growth, and (62)Ni bioaccumulation), and presence of TSS exposures demonstrated both protective and synergistic effects on H. azteca and L. stagnalis. (62)Ni trophic transfer from food to H. azteca and L. stagnalis was negligible; however, bioaccumulating (62)Ni was attributed to (62)Ni-water ((62)Ni flux from food), (62)Ni-TSS, and (62)Ni-food. Overall, H. azteca and L. stagnalis Ni compartment toxicity increased in the following order: Ni-water >> Ni-sediment >> Ni-all (water, sediment, food) >> Ni-food. PMID- 26552545 TI - Do cytostatic drugs reach drinking water? The case of mycophenolic acid. AB - Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17-56.2 ng L(-1)). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. PMID- 26552546 TI - Parenting and family support within a broad child abuse prevention strategy: Child maltreatment prevention can benefit from public health strategies. PMID- 26552547 TI - Integrated environmental policy: Chemicals and additives in textiles. PMID- 26552548 TI - Laparoscopic Roux-en-Y gastric bypass reversal. PMID- 26552549 TI - Comment on the REDUCE trial article: Is it really as good as it sounds? PMID- 26552550 TI - Comment on: Influence of intraoperative hypotension on leaks after sleeve gastrectomy. PMID- 26552551 TI - Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development. AB - BACKGROUND: Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells. METHODS: The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo. RESULTS: Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-kappaB and Akt signaling pathways. CONCLUSIONS: All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells. PMID- 26552553 TI - Atrial fibrillation with Wolff-Parkinson-White syndrome in epilepsy: A potentially fatal combination. PMID- 26552552 TI - Infant frontal electroencephalogram asymmetry and negative emotional reactivity as predictors of toddlerhood effortful control. AB - Given the importance of children's self-regulation, relations were examined between two fundamental components of self-regulation, specifically temperamentally based reactivity and regulation. Infant negative emotional reactivity and regulation, measured via frontal electroencephalogram (EEG) asymmetry, were examined as potential precursors to understanding toddlerhood regulation, conceptualized as effortful control. Our longitudinal design allowed for examination of two perspectives on the interplay of reactivity and regulation, namely that (a) early negative affectivity interferes with the development of later regulation and (b) regulation is necessary to modulate negative affectivity and, thus, would buffer the effects of negative affectivity on later regulation. Mother-child dyads participated in a three-wave longitudinal study. Baseline frontal EEG asymmetry was assessed at 10months (T1). Mothers rated children's negative reactivity at both 10 and 24months (T2). Children's effortful control, measured at 30-36months (T3), was a composite score of maternal ratings and observed behavior during a snack delay. Negative affectivity was related to effortful control; however, significant interactions between negative affect and frontal EEG asymmetry were found. Higher levels of negative affectivity at both T1 and T2 were associated with lower levels of effortful control at T3, but only for toddlers who also had right frontal EEG asymmetry. Negative affectivity was not associated with effortful control for the left frontal EEG asymmetry group. Our moderation findings highlight the complex relations of negative affect and frontal EEG asymmetry in understanding children's development of self-regulation, specifically effortful control. The interaction between early reactivity and physiological regulation indicates that both may be important precursors of effortful control. PMID- 26552554 TI - Drop attacks, falls and atonic seizures in the Video-EEG monitoring unit. AB - PURPOSE: We set out to determine clinical and EEG features of seizures presenting with falls, epileptic drop attacks and atonia in the video EEG monitoring unit. METHODS: We searched the video EEG monitoring reports over a 5-year-period for the terms "drop", "fall" and "atonic". RESULTS: Seizures presenting as epileptic drop attacks, falls or atonia were found in 23/1112 (2%) admissions. About half of the patients suffering from these seizure types had developmental delay and learning difficulties and in half of the patients a lesion was seen on MRI which was often frontal. The presumed epileptogenic zone was frontal in many cases (43%), unclear with regards to a region or multifocal in 48% and posterior temporal/occipital in 2 patients (9%). EEG patterns recorded were paroxysmal fast activity, spike and wave discharges and EEG attenuation. Seizure related falls were seen in 8 cases (34%) with injuries recorded during Video EEG monitoring in half of those. CONCLUSION: Clinical and EEG features outlined here can help the clinician to recognise patients at risk for these devastating seizure types. PMID- 26552555 TI - Termination patterns of complex partial seizures: An intracranial EEG study. AB - PURPOSE: While seizure onset patterns have been the subject of many reports, there have been few studies of seizure termination. In this study we report the incidence of synchronous and asynchronous termination patterns of partial seizures recorded with intracranial arrays. METHODS: Data were collected from patients with intractable complex partial seizures undergoing presurgical evaluations with intracranial electrodes. Patients with seizures originating from mesial temporal and neocortical regions were grouped into three groups based on patterns of seizure termination: synchronous only (So), asynchronous only (Ao), or mixed (S/A, with both synchronous and asynchronous termination patterns). RESULTS: 88% of the patients in the MT group had seizures with a synchronous pattern of termination exclusively (38%) or mixed (50%). 82% of the NC group had seizures with synchronous pattern of termination exclusively (52%) or mixed (30%). In the NC group, there was a significant difference of the range of seizure durations between So and Ao groups, with Ao exhibiting higher variability. Seizures with synchronous termination had low variability in both groups. CONCLUSIONS: Synchronous seizure termination is a common pattern for complex partials seizures of both mesial temporal or neocortical onset. This may reflect stereotyped network behavior or dynamics at the seizure focus. PMID- 26552556 TI - A retrospective cross-sectional study of the prevalence of generalized convulsive status epilepticus in traumatic brain injury: United States 2002-2010. AB - PURPOSE: To determine the incidence, predictors, and outcomes of generalized convulsive status epilepticus (GCSE) in traumatic brain injury (TBI) patients. METHODS: We conducted a retrospective cross-sectional study of adult patients with acute TBI using the 2002-2010 Nationwide Inpatient Sample (NIS) database of USA. We used multivariable logistic regression analyses to identify independent predictors of GCSE in patients with TBI and to determine the impact of GCSE on outcomes (in-hospital mortality, length of stay, total hospital charges, and discharge disposition). RESULTS: Among 1,457,869 patients hospitalized with TBI, 2315 (0.16%) had GCSE. In-hospital mortality was significantly higher in patients with GCSE (32.5% vs. 9.6%; unadjusted OR 4.54, 95% CI 4.16-4.96; p<0.001; adjusted OR 3.41; 95% CI 3.09-3.76 p<0.001). Patients with GCSE had longer length of stay (17.3 +/- 21.9 vs. 6.8 +/- 11.1 days; p<0.001), higher total hospital charges ($147,415 +/- 162,319 vs. $54,041 +/- 90,524; p<0.001), and were less likely to be discharged home (19.8% vs. 52.7%; p<0.001). Using multivariable logistic regression analysis, age >35 years (OR 2.15; 95% CI 1.87-2.47), CNS infections (OR 4.86; 95% CI 3.70-6.38), anoxic brain injury (OR 9.54; 95% CI 8.10 11.22), and acute ischemic stroke (OR 4.09; 95% CI 3.41-4.87) were independent predictors of GCSE in TBI patients. Epilepsy was an independent negative predictor of GCSE (OR 0.74; 95% CI 0.55-0.99). CONCLUSION: Despite its low incidence, GCSE in TBI patients was associated with worse outcomes with threefold higher in-hospital mortality, prolonged hospitalization, higher hospital charges, and worse discharge disposition. Surprisingly, epilepsy is a negative predictor of GCSE in this population. PMID- 26552557 TI - Proton magnetic resonance spectroscopy in focal cortical dysplasia at 3T. AB - PURPOSE: Focal cortical dysplasia (FCD) type II is a frequent cause of medically intractable epilepsy. On conventional MRI diagnosis may be difficult. The purpose of our study was to assess the metabolic characteristics of MRI-typical or neuropathologically confirmed FCD II lesions at 3T. METHODS: In a prospective study, 13 patients with drug-resistant epilepsy and MRI diagnosis of FCD II (seven neuropathologically confirmed) were investigated by single-volume proton magnetic resonance spectroscopy ((1)H MRS). We performed an intra-individual comparison placing spectroscopic volumes of interest in the lesion and in the apparently normal contralateral hemisphere. Spectroscopic results were correlated with clinical data. RESULTS: Matched pair analysis revealed a significant increase in absolute choline (Cho) concentration in the lesion volume (+32%, p=0.015) compared to the control volume. This increase was associated with a significant decrease in N-acetyl-aspartate (NAA) concentration (-13%; p=0.008). Mean myo-inositol (Ins) levels were distinctly (+36%) but not significantly (p=0.051) elevated. Lesional creatine (Cr) concentration correlated significantly with the frequency of seizures (Spearman-Rho r=0.898; p=0.002), while concentrations of NAA, Cho and Ins did not correlate with clinical or imaging parameters. CONCLUSION: MR spectroscopy revealed a characteristic metabolic pattern in FCD II lesions that helps to distinguish normal from epileptogenic tissue. PMID- 26552558 TI - GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case-control study. AB - PURPOSE: Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients. METHODS: GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined. RESULTS: The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1 null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype. CONCLUSIONS: GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients. PMID- 26552560 TI - Are psychogenic nonepileptic seizures genetically determined? It is time to explore! PMID- 26552559 TI - Gender differences in depression, but not in anxiety in people with epilepsy. AB - PURPOSE: Anxiety and depression are frequent comorbidities in people with epilepsy (PWE), but possible gender differences are often neglected. The aim of the present study was to analyze if men and women with epilepsy differ with regard to anxiety and depressive symptoms and to identify possible predictors. METHODS: Adult consecutive PWE (N=302; 53% women) completed self-report questionnaires, including the depression module of the Patient Health Questionnaire (PHQ-9), the anxiety module of the Hospital Anxiety and Depression Scale (HADS-A) and the subscales "medication effects" and "seizure worry" of the Patient-weighted Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P). RESULTS: There was no gender difference in extent of anxiety (p=.532), which was mainly due to higher anxiety levels in men compared to the general population. The gender difference in depressive symptoms was significant (p=.009), with female patients being more affected. The most important predictors for anxiety and depressive symptoms were detrimental effects of medication (QOL medication effects) and of seizure worry (QOL seizure worry). Moreover, these predictors were more closely associated with anxiety and depressive symptoms in men. CONCLUSION: Future intervention studies could show whether providing more information about the illness and medication effects may improve anxiety and depression. Our results suggest that such interventions should be tailored to the different needs of men and women. PMID- 26552561 TI - Steroids efficacy in the acute management of seizure clusters in one case of PCDH19 female epilepsy. PMID- 26552562 TI - Use of suggestion methods to induce psychogenic non-epileptic seizures. PMID- 26552563 TI - Eating epilepsy characterised by late-onset epileptic spasms in a case of Cri du chat syndrome. PMID- 26552564 TI - A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. AB - PURPOSE: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). METHODS: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. RESULTS: Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a >= 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of >= 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within +/- 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (>= 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. CONCLUSIONS: The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. PMID- 26552565 TI - Phenotyping juvenile myoclonic epilepsy. Praxis induction as a biomarker of unfavorable prognosis. AB - PURPOSE: Juvenile myoclonic epilepsy (JME) is a heterogeneous syndrome with seizures presenting typical fluctuation in diurnal cycle and relation with awakening. Few publications have approached clinical expressions of praxis induction (PI) in the nosology of JME as well as its impact on outcome. The aim of this study is to characterize PI as the only reflex trait in JME and its relation with prognosis. METHOD: JME with PI reported on a questionnaire and confirmed by video-EEG testing (Group 1, 20 patients) were compared with JME without any reflex epileptic trait (Group 2, 25 patients) and followed for a mean of 7.82 years (SD=3.98). Circadian distribution and frequency of seizures were assessed in a diary. Patients also had psychiatric evaluation. RESULTS: Prevalence of PI was 20/133 (15%) JME patients, and was predominant in males (1.5 male: 1 female; OR 13; p=0.042). Among Group 1 patients, only 2/20 presented seizures exclusively in the morning (p=0.013), and none, exclusively on awakening (p<0.001). PI patients had worse prognosis regarding control of myocloni (p=0.02) and absences (p=0.01); only 7/20 (35.0%) could be treated with VPA in monotherapy (p=0.01). At the last follow-up, 2/20 (10.0%) of Group 1 and 10 (40.0%) of Group 2 patients were free of all three seizure types (p=0.02). Even though relative risk of stress as a precipitant of seizures increased 3.82 times in Group 1, psychiatric comorbidities were not different between groups. CONCLUSION: PI reflex trait in JME is related to seizures without preferential circadian occurrence and reduced response to antiepileptic drugs. PMID- 26552566 TI - Safety and tolerability of an oral zonisamide loading dose. AB - PURPOSE: There are a limited number of anticonvulsant medications that can be administered with an oral loading dose in order to rapidly achieve an effective serum level, and most of these have associated adverse effects. Zonisamide is approved for the treatment of partial onset epilepsy, and is used in practice for both generalized and partial onset epilepsy. It is generally well-tolerated, has a long half-life, and can be administered once daily. Unfortunately, the recommended titration schedule for initiating therapy takes several weeks to reach target dose and therapeutic serum levels. METHODS: We initiated zonisamide therapy using a large initial dose of zonisamide in 32 patients in our epilepsy monitoring unit over the past four years. RESULTS: Adverse effects were rare and involved nausea/vomiting (9.4%) or drowsiness (6.3%). In patients where serum levels were available for review, therapeutic or near-therapeutic levels were achieved after an oral load of 600-900 mg given as divided doses over a 6-12h period. CONCLUSION: This report is the first to suggest a method of rapidly initiating zonisamide therapy, achieving therapeutic serum levels in a shorter time frame, with an adverse effect profile similar to the recommended titration schedule. PMID- 26552567 TI - Jeavons syndrome as an occipital cortex initiated generalized epilepsy: Further evidence from a patient with a photic-induced occipital seizure. PMID- 26552568 TI - Concomitant lamotrigine use is associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy. AB - PURPOSE: Anti-epileptic drugs (AEDs) and the ketogenic diet (KD) are often used concomitantly in children with refractory epilepsy. It has been hypothesised that certain AEDs may interfere with KD. The purpose of this study was to elucidate relationships between efficacy of KD and use of specific AEDs. METHODS: A retrospective study was performed in 71 children with refractory epilepsy starting the KD between 2008 and 2014 in Erasmus University Hospital Sophia Children's Hospital. Efficacy of the KD (defined as 50% seizure reduction) was evaluated after three months of treatment and related to the AEDs used. RESULTS: The KD was successful after three months in 61% of the children (N=71). Efficacy was significantly reduced if children (n=16) used lamotrigine (31%) at diet initiation or in the course of the diet, compared to other antiepileptic drugs (69%) (p=0.006). In comparison to children using other antiepileptic drugs, the percentage of children that had adequate ketosis was significantly reduced in case of lamotrigine use (p=0.049). CONCLUSION: Lamotrigine treatment during KD is associated with a decreased efficacy of the KD. PMID- 26552569 TI - Epilepsy and chromosome 18 abnormalities: A review. AB - PURPOSE: To analyze the various types of epilepsy in subjects with chromosome 18 aberrations in order to define epilepsy and its main clinical, electroclinical and prognostic aspects in chromosome 18 anomalies. METHODS: A careful overview of recent works concerning chromosome 18 aberrations and epilepsy has been carried out considering the major groups of chromosomal 18 aberrations, identified using MEDLINE and EMBASE database from 1980 to 2015. RESULTS: Epilepsy seems to be particularly frequent in patients with trisomy or duplication of chromosome 18 with a prevalence of up to 65%. Approximately, over half of the patients develop epilepsy during the first year of life. Epilepsy can be focal or generalized; infantile spasms have also been reported. Brain imagines showed anatomical abnormalities in 38% of patients. Some antiepileptic drugs as valproic acid and carbamazepine were useful for treating seizures although a large majority of patients need polytherapy. CONCLUSION: Children with chromosomal 18 abnormalities can present different types of epilepsy, more frequently focal seizures in individuals with 18q- deletion syndrome, while both complex partial seizures and generalized tonic-clonic seizures have been described in patients who suffer for trisomy 18. Outcome in term of seizures frequency and duration seems to be variable and epilepsy is drug resistant in half of the children, especially in children with trisomy 18 and generalized epilepsy. PMID- 26552570 TI - Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery. AB - PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post surgical follow-up. METHODS: We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. RESULTS: TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. CONCLUSIONS: Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up. PMID- 26552571 TI - Malformations of cortical development and epilepsy: A cohort of 150 patients in western China. AB - PURPOSE: Malformations of cortical development (MCDs) are abnormalities of the cerebral cortex that arise from abnormal formation of the cortical plate, and have become increasingly identified as an important etiology for refractory epilepsy. Little is known about the spectrum, distribution and clinical features of MCDs, especially in resource-limited regions. This study investigates the distribution of MCDs and compares the clinical features and long-term prognosis between the two forms of MCDs: Simple and Multiple. METHOD: One hundred and fifty epilepsy patients (138 adults, 12 pediatric patients) with radiologically diagnosed MCDs were identified at a tertiary epilepsy center in western China. Patients were divided into three subtypes according to the Barkovich classification. They were further divided into either Simple or Multiple MCD forms based on whether they had a single type of MCDs or other co-existing developmental brain abnormalities. RESULTS: The most common type of MCD is focal cortical dysplasia. We found perinatal insults more common in group III patients. Multiple MCD was identified in 36 of 150 patients, and was associated with higher rates of delayed milestones (p=0.005), cognitive impairment (p=0.023) and neurological deficits (p=0.002) compared to Simple MCD. Extra-temporal epilepsy was more commonly seen among individuals with Multiple MCD (p=0.017). Participants with Multiple MCD were younger at time of seizure onset (p=0.003) and at assessment (p=0.002), had a lower seizure-free rate (p=0.033) and had worse outcomes overall. Patients with heterotopias were more commonly associated with other abnormalities. CONCLUSION: MCDs are a critical cause of epilepsy and pose a big challenge for resource-limited countries. Imaging techniques are crucial in diagnosing and classifying cortical deformities. Multiple malformations lead to more severe clinical features and worse prognosis. Identifying and classifying MCDs can help physicians to better estimate patient prognosis and seek the best, individualized therapeutic options. PMID- 26552572 TI - Magnesium sulfate for non-eclamptic status epilepticus. AB - BACKGROUND: Our goal was to perform a systematic review of the literature on the use of intravenous magnesium sulfate (MgSO4) for non-eclamptic status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: We identified 19 original articles. A total of 28 patients were described in these articles with 11 being adult, 9 being pediatric, and 8 of unknown age. Seizure reduction/control with IV MgSO4 occurred in 14 of the 28 patients (50.0%), with 2 (7.1%) and 12 (42.9%) displaying partial and complete responses respectively. Seizures recurred upon withdrawal of MgSO4 therapy in 50% of the patients whom had reduction/control of their SE/RSE. Three patients had recorded adverse events related to MgSO4 therapy. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to suggest a trend towards improved seizure control with the use of intravenous MgSO4 for non eclamptic RSE. Routine use of IV MgSO4 in non-eclamptic SE/RSE cannot be recommended at this time. Further prospective study of this drug is required in order to determine its efficacy as an anti-epileptic in this setting. PMID- 26552573 TI - Seizure reporting technologies for epilepsy treatment: A review of clinical information needs and supporting technologies. AB - This review surveys current seizure detection and classification technologies as they relate to aiding clinical decision-making during epilepsy treatment. Interviews and data collected from neurologists and a literature review highlighted a strong need for better distinguishing between patients exhibiting generalized and partial seizure types as well as achieving more accurate seizure counts. This information is critical for enabling neurologists to select the correct class of antiepileptic drugs (AED) for their patients and evaluating AED efficiency during long-term treatment. In our questionnaire, 100% of neurologists reported they would like to have video from patients prior to selecting an AED during an initial consultation. Presently, only 30% have access to video. In our technology review we identified that only a subset of available technologies surpassed patient self-reporting performance due to high false positive rates. Inertial seizure detection devices coupled with video capture for recording seizures at night could stand to address collecting seizure counts that are more accurate than current patient self-reporting during day and night time use. PMID- 26552574 TI - Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review. AB - OBJECTIVES: There is increasing evidence that physical activity (PA) positively affects cognitive function (CF). Existing research has focussed on this association in children and the elderly, with less research available in young to middle-aged adults who constitute a substantial proportion of the population. DESIGN: A systematic review investigating the relationship between habitual PA (>=12 months) and CF in young to middle-aged adults (18-50 years). METHODS: A search was conducted using AMED, CINAHL, MEDLINE, PsychINFO, AUSPORT MED and SPORTDiscus databases. Eligible studies had to report descriptive statistics for CF and PA levels in healthy participants 18-50 years. Effect sizes (ES) (Hedges g) were calculated where possible. RESULTS: The initial search netted 26,988 potentially relevant manuscripts, with four more identified through hand searching. Fourteen were included for review. A range of validated platforms assessed CF across three domains: executive function (12 studies), memory (four studies) and processing speed (seven studies). Habitual PA was assessed via questionnaire/self-report methods (n=13, 8 validated) or accelerometers (n=1). In studies of executive function, five found a significant ES in favour of higher PA, ranging from small to large. Although three of four studies in the memory domain reported a significant benefit of higher PA, there was only one significant ES, which favoured low PA. Only one study examining processing speed had a significant ES, favouring higher PA. CONCLUSIONS: A limited body of evidence supports a positive effect of PA on CF in young to middle-aged adults. Further research into this relationship at this age stage is warranted. PMID- 26552575 TI - To feel strong in an unfamiliar situation; Patients' lived experiences of neurosurgical intensive care. A qualitative study. AB - AIM: The aim of this study was to explore the lived experiences of conscious patients in neurosurgical intensive care. METHOD: Data collection was performed by qualitative interviews using an interview guide. Eleven former patients, seven women and four men, were interviewed two to 14 months after discharge. The interviews were recorded and transcribed verbatim and analysed using an interpretive phenomenological approach. FINDINGS: The analysis revealed three themes: To feel safe in an unfamiliar situation, to experience strains and limitations, and to be confirmed as a human being. These three themes culminated in the essence: To feel strong in an unfamiliar situation. Patients experienced a soothing environment where, despite strains, they felt safe being cared for in a ward with specialised medical treatment. When mental and physical strains decreased during the period of care, they experienced the ability to cope with the simplest tasks as a sign of regained identity. CONCLUSION: Patients' main experience during intensive care was security. Security along with human contact and interaction with staff and next of kin made the patients feel strengthened as human beings in an unfamiliar situation. The fact that the patients were conscious enabled them to understand their situation and to experience security. PMID- 26552576 TI - Early maternal loss affects social integration of chimpanzees throughout their lifetime. AB - The long-term effects of early adverse experiences on later psychosocial functioning are well described in humans, but sparsely documented for chimpanzees. In our earlier studies, we investigated the effects of maternal and social deprivation on three groups of ex-laboratory chimpanzees who experienced either an early or later onset of long-term deprivation. Here we expand our research by adding data on subjects that came from two stable zoo groups. The groups comprised of early maternally deprived wild-caught chimpanzees and non deprived zoo-born chimpanzees. We found that compared to zoo chimpanzees, ex laboratory chimpanzees were more restricted regarding their association partners in the newly formed groups, but not during their second year of group-life, indicating that social stability has an important influence on the toleration of association partners close-by. Social grooming activity, however, was impaired in early long-term deprived ex-laboratory chimpanzees as well as in early maternally deprived zoo chimpanzees compared to non-deprived zoo chimpanzees. Thus, we conclude that early maternal loss has lifelong effects on the social integration of chimpanzees which becomes evident in their grooming networks. Although the retrospective nature of our study prevents a clear causal explanation, our results are of importance for understanding the development of social competence in chimpanzees. PMID- 26552577 TI - Design, synthesis and evaluation of N-aryl-glyoxamide derivatives as structurally novel bacterial quorum sensing inhibitors. AB - Bacteria cooperatively regulate the expression of many phenotypes through a mechanism called quorum sensing (QS). Many Gram-negative bacteria use an N-acyl homoserine lactone (AHL)-mediated QS system to control biofilm formation and virulence factor production. In recent years, quorum sensing inhibitors (QSIs) have become attractive tools to overcome antimicrobial resistance exhibited by various pathogenic bacteria. In the present study, we report the design and synthesis of novel N-arylisatin-based glyoxamide derivatives via the ring-opening reaction of N-aryl isatins with cyclic and acylic amines, and amino acid esters. The QSI activity of the synthesized compounds was determined in the LasR expressing Pseudomonas aeruginosa MH602 and LuxR-expressing Escherichia coli MT102 reporter strains. Compounds 31 and 32 exhibited the greatest QSI activity in P. aeruginosa MH602, with 48.7% and 42.7% reduction in QS activity at 250 MUM, respectively, while compounds 31 and 34 showed 73.6% and 43.7% QSI activity in E. coli MT102. In addition, the ability of these compounds to inhibit the production of pyocyanin in P. aeruginosa (PA14) was also determined, with compound 28 showing 47% inhibition at 250 MUM. Furthermore, computational docking studies were performed on the LasR receptor protein of P. aeruginosa, which showed that formation of a hydrogen bonding network played a major role in influencing the QS inhibitory activity. We envisage that these novel non-AHL glyoxamide derivatives could become a new tool for the study of QS and potentially for the treatment of bacterial infections. PMID- 26552578 TI - Unique roles played by Acid-sensing ion channel 2. AB - The discovery of Acid-sensing ion channels (ASICs) provided us the theoretical basis to understand the pathological acidic environment. They belong to the degenerin/epithelial Na+ channel family and function once extracellular pH decreases to a certain level, and this characteristic make them spotlights in the regulation or response of pH change. As a regulatory system, keeping the intra- and extra-balance seems to be significant for ASICs, in which ASIC2 plays an important role. We surprisingly noticed that ASIC2 owns some distinctive properties, including its inter-system regulation, specific distribution and transporting patterns, influence on cell migration and the unique role in mechanosensitivity. Therefore, to conclude the functions and characterisitics of ASIC2 indeed assist the understanding of interaction among ASICs subunits and the regulation from extracellular environment to ASICs. PMID- 26552580 TI - Correction: Hard-templating of Prussian blue analogues in mesoporous silica and organosilica. AB - Correction for 'Hard-templating of Prussian blue analogues in mesoporous silica and organosilica' by Pei-Xi Wang, et al., Dalton Trans., 2015, 44, 14724-14731. PMID- 26552579 TI - Unpacking the key components of a programme to improve the timeliness of hip fracture care: a mixed-methods case study. AB - BACKGROUND: Delay to surgery for patients with hip fracture is associated with higher incidence of post-operative complications, prolonged recovery and length of stay, and increased mortality. Therefore, many health care organisations launch improvement programmes to reduce the wait for surgery. The heterogeneous application of similar methods, and the multifaceted nature of the interventions, constrain the understanding of which method works, when, and how. In complex acute care settings, another concern is how changes for one patient group influence the care for other groups. We therefore set out to analyse how multiple components of hip-fracture improvement efforts aimed to reduce the time to surgery influenced that time both for hip-fracture patients and for other acute surgical orthopaedic inpatients. METHODS: This study is an observational mixed methods single case study of improvement efforts at a Swedish acute care hospital, which triangulates control chart analysis of process performance data over a five year period with interview, document, and non-participant observation data. RESULTS: The improvement efforts led to an increase in the monthly percentage of hip-fracture patients operated within 24 h of admission from an average of 47% to 83%, with performance predictably ranging between 67% and 98% if the process continues unchanged. Meanwhile, no significant changes in lead time to surgery for other acute surgical orthopaedic inpatients were observed. Interview data indicated that multiple intervention components contributed to making the process more reliable. The triangulation of qualitative and quantitative data, however, indicated that key changes that improved performance were the creation of a process improvement team and having an experienced clinician coordinate demand and supply of surgical services daily and enhance pre operative patient preparation. CONCLUSIONS: Timeliness of surgery for patients with hip fracture in a complex hospital setting can be substantially improved without displacing other patient groups, by involving staff in improvement efforts and actively managing acute surgical procedures. PMID- 26552581 TI - APOE-epsilon4 selectively modulates posteromedial cortex activity during scene perception and short-term memory in young healthy adults. AB - Apolipoprotein E (APOE) epsilon4 is a major genetic risk factor for Alzheimer's disease (AD), yet the mechanisms by which APOE-epsilon4 influences early-life brain function, and hence, in turn, risk for later-life AD, are poorly understood. Here, we report a novel, and selective, pattern of functional brain activity alteration in healthy young adult human APOE-epsilon4 carriers. Our findings suggest that APOE-epsilon4 may influence vulnerability to poorer later life cognitive health via its effect on posteromedial cortex (PMC), a hub region within a brain network involved in spatial processing, and necessary for episodic memory. In two neuroimaging tasks, APOE-epsilon4 carriers showed an inability to effectively modulate PMC during scene, but not face and object, working memory and perception. This striking pattern overlaps both functionally and topographically, with the earliest cognitive deficits seen in clinical AD, as well as reported alterations in the default network in amyloid-positive individuals at increased risk of AD. PMID- 26552582 TI - Hepatic myofibroblasts derived from Schistosoma mansoni-infected mice are a source of IL-5 and eotaxin: controls of eosinophil populations in vitro. AB - BACKGROUND: Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin. METHODS AND RESULTS: The secretory activity of GR-MF was detected after TGF-beta and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity. CONCLUSION: These results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis. PMID- 26552583 TI - The genetics of feed conversion efficiency traits in a commercial broiler line. AB - Individual feed conversion efficiency (FCE) is a major trait that influences the usage of energy resources and the ecological footprint of livestock production. The underlying biological processes of FCE are complex and are influenced by factors as diverse as climate, feed properties, gut microbiota, and individual genetic predisposition. To gain an insight to the genetic relationships with FCE traits and to contribute to the improvement of FCE in commercial chicken lines, a genome-wide association study was conducted using a commercial broiler population (n = 859) tested for FCE and weight traits during the finisher period from 39 to 46 days of age. Both single-marker (generalized linear model) and multi-marker (Bayesian approach) analyses were applied to the dataset to detect genes associated with the variability in FCE. The separate analyses revealed 22 quantitative trait loci (QTL) regions on 13 different chromosomes; the integration of both approaches resulted in 7 overlapping QTL regions. The analyses pointed to acylglycerol kinase (AGK) and general transcription factor 2 I (GTF2I) as positional and functional candidate genes. Non-synonymous polymorphisms of both candidate genes revealed evidence for a functional importance of these genes by influencing different biological aspects of FCE. PMID- 26552584 TI - A Hybrid Circuit for Spoof Surface Plasmons and Spatial Waveguide Modes to Reach Controllable Band-Pass Filters. AB - We propose a hybrid circuit for spoof surface plasmon polaritons (SPPs) and spatial waveguide modes to develop new microwave devices. The hybrid circuit includes a spoof SPP waveguide made of two anti-symmetric corrugated metallic strips and a traditional substrate integrated waveguide (SIW). From dispersion relations, we show that the electromagnetic waves only can propagate through the hybrid circuit when the operating frequency is less than the cut-off frequency of the SPP waveguide and greater than the cut-off frequency of SIW, generating efficient band-pass filters. We demonstrate that the pass band is controllable in a large range by designing the geometrical parameters of SPP waveguide and SIW. Full-wave simulations are provided to show the large adjustability of filters, including ultra wideband and narrowband filters. We fabricate a sample of the new hybrid device in the microwave frequencies, and measurement results have excellent agreements to numerical simulations, demonstrating excellent filtering characteristics such as low loss, high efficiency, and good square ratio. The proposed hybrid circuit gives important potential to accelerate the development of plasmonic integrated functional devices and circuits in both microwave and terahertz frequencies. PMID- 26552585 TI - Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking. AB - OBJECTIVE: Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. METHODS: We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. RESULTS: Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. CONCLUSIONS: We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays. PMID- 26552587 TI - Correction: biocompatible organic charge transfer complex nanoparticles based on a semi-crystalline cellulose template. AB - Correction for 'Biocompatible organic charge transfer complex nanoparticles based on a semi-crystalline cellulose template' by Atsushi Nagai et al., Chem. Commun., 2015, 51, 11868-11871. PMID- 26552586 TI - Psychological job strain, social support at work and daytime secretion of dehydroepiandrosterone (DHEA) in healthy female employees: cross-sectional analyses. AB - Evidence is limited concerning the influences of high psychological job strain and low social support at work on daytime secretion of dehydroepiandrosterone (DHEA), which demonstrates anti-cortisol effects. We carried out a cross sectional study to examine the associations of job strain and social support with daytime secretion amounts of DHEA and cortisol and daytime variation of the cortisol-to-DHEA ratio (C/D ratio) in healthy female workers. Study subjects comprised 115 healthy female nursery school teachers. Area under the curve with respect to ground (AUCG) of salivary DHEA, cortisol and C/D ratio was calculated for estimation of daytime secretion and variation. Social support scores were negatively associated with daytime DHEA secretion (standardized partial regression coefficient = -0.343, P < 0.001 by multiple linear regression analysis). This association remained significant when daytime cortisol secretion was additionally adjusted. Social support was not associated with daytime variation of the C/D ratio. Significant association between social support and daytime cortisol secretion was not confirmed. Job strain was not associated with DHEA, cortisol or the C/D ratio. In summary, we found that daytime DHEA secretion was increased in healthy workers with low social support, perhaps independent of daytime cortisol secretion. PMID- 26552588 TI - Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves. AB - Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress. PMID- 26552589 TI - Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Deltaexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology. AB - Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer's disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue-derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins. The first line expresses oligomerogenic mutant APP(E693Q) inside neurons, leading to the accumulation of amyloid beta (Abeta) oligomers and behavioral impairment, but never develops parenchymal fibrillar amyloid deposits. The second line expresses APP(KM670/671NL)/PSEN1(Deltaexon9) in neurons and accumulates fibrillar Abeta amyloid and amyloid plaques accompanied by neuritic dystrophy and behavioral impairment. We performed RNA sequencing analyses of the dentate gyrus and entorhinal cortex from each line and from wild-type mice. We then performed an integrative genomic analysis to identify dysregulated molecules and pathways, comparing transgenic mice with wild-type controls as well as to each other. We also compared these results with datasets derived from human AD brain. Differential gene and exon expression analysis revealed pervasive alterations in APP/Abeta metabolism, epigenetic control of neurogenesis, cytoskeletal organization and extracellular matrix (ECM) regulation. Comparative molecular analysis converged on FMR1 (Fragile X Mental Retardation 1), an important negative regulator of APP translation and oligomerogenesis in the post-synaptic space. Integration of these transcriptomic results with human postmortem AD gene networks, differential expression and differential splicing signatures identified significant similarities in pathway dysregulation, including ECM regulation and neurogenesis, as well as strong overlap with AD-associated co-expression network structures. The strong overlap in molecular systems features supports the relevance of these findings from the AD mouse models to human AD. PMID- 26552592 TI - A novel approach to PTSD modeling in rats reveals alternating patterns of limbic activity in different types of stress reaction. AB - Human reactions to trauma exposure are extremely diverse, with some individuals exhibiting only time-limited distress and others qualifying for posttraumatic stress disorder diagnosis (PTSD). Furthermore, whereas most PTSD patients mainly display fear-based symptoms, a minority of patients display a co-morbid anhedonic phenotype. We employed an individual profiling approach to model these intriguing facets of the psychiatric condition in underwater-trauma exposed rats. Based on long-term assessments of anxiety-like and anhedonic behaviors, our analysis uncovered three separate phenotypes of stress response; an anxious, fear-based (38%), a co-morbid, fear-anhedonic (15%), and an exposed-unaffected group (47%). Immunohistochemical assessments for cellular activation (c-Fos) and activation of inhibition (c-Fos+GAD67) revealed a differential involvement of limbic regions and distinct co-activity patterns for each of these phenotypes, validating the behavioral categorization. In accordance with recent neurocognitive hypotheses for posttraumatic depression, we show that enhanced pretrauma anxiety predicts the progression of posttraumatic anhedonia only in the fear-anhedonic phenotype. PMID- 26552590 TI - The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. AB - Accumulating research demonstrates the potential of intranasal delivery of psychopharmacological agents to treat a range of psychiatric disorders and symptoms. It is believed that intranasal administration offers both direct and indirect pathways to deliver psychopharmacological agents to the central nervous system. This administration route provides a unique opportunity to repurpose both old drugs for new uses and improve currently approved drugs that are indicated for other administration routes. Despite this promise, however, the physiology of intranasal delivery and related assumptions behind the bypassing of the blood brain barrier is seldom considered in detail in clinical trials and translational research. In this review, we describe the current state of the art in intranasal psychopharmacological agent delivery research and current challenges using this administration route, and discuss important aspects of nose-to-brain delivery that may improve the efficacy of these new therapies in future research. We also highlight current gaps in the literature and suggest how research can directly examine the assumptions of nose-to-brain delivery of psychopharmacological agents in humans. PMID- 26552591 TI - Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. AB - Depression is associated with alterations in corticostriatal reward circuitry. One pathophysiological pathway that may drive these changes is inflammation. Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward related brain regions in association with reduced motivation and anhedonia. Accordingly, we examined whether increased inflammation in depression affects corticostriatal reward circuitry to lead to deficits in motivation and goal directed motor behavior. Resting-state functional magnetic resonance imaging was conducted on 48 medically stable, unmedicated outpatients with major depression. Whole-brain, voxel-wise functional connectivity was examined as a function of CRP using seeds for subdivisions of the ventral and dorsal striatum associated with motivation and motor control. Increased CRP was associated with decreased connectivity between ventral striatum and ventromedial prefrontal cortex (vmPFC) (corrected P<0.05), which in turn correlated with increased anhedonia (R=-0.47, P=0.001). Increased CRP similarly predicted decreased dorsal striatal to vmPFC and presupplementary motor area connectivity, which correlated with decreased motor speed (R=0.31 to 0.45, P<0.05) and increased psychomotor slowing (R=-0.35, P=0.015). Of note, mediation analyses revealed that these effects of CRP on connectivity mediated significant relationships between CRP and anhedonia and motor slowing. Finally, connectivity between striatum and vmPFC was associated with increased plasma interleukin (IL)-6, IL-1beta and IL-1 receptor antagonist (R=-0.33 to -0.36, P<0.05). These findings suggest that decreased corticostriatal connectivity may serve as a target for anti-inflammatory or pro-dopaminergic treatment strategies to improve motivational and motor deficits in patients with increased inflammation, including depression. PMID- 26552593 TI - MicroRNA367 negatively regulates the inflammatory response of microglia by targeting IRAK4 in intracerebral hemorrhage. AB - BACKGROUND: Intracerebral hemorrhage (ICH) induces microglial activation and the release of inflammatory cytokines, leading to inflammation in the brain. IRAK4, an essential component of the MyD88-dependent pathway, activates subsets of divergent signaling pathways in inflammation. METHODS: In the experiment, microglia were stimulated with erythrocyte lysates, and then miR-367, IRAK4, NF KB activation and downstream proinflammatory mediator production were analyzed. In addition, inflammation, brain edema, and neurological functions in ICH mice were also assessed. RESULTS: Here, we report that ICH downregulated miR-367 expression but upregulated IRAK4 expression in primary microglia. We also demonstrate that miR-367 suppressed IRAK4 expression by directly binding its 3' untranslated region. MiR-367 inhibited NF-KB activation and downstream proinflammatory mediator production. Knocking down IRAK4 in microglia significantly decreased the IRAK4 expression and inhibited the NF-KB activation and the downstream production of proinflammatory mediators. In addition, our results indicate that miR-367 could inhibit expression of proinflammatory cytokines, reduce brain edema, and improve neurological functions in ICH mice. CONCLUSIONS: In conclusion, our study demonstrates that miR-367/IRAK4 pathway plays an important role in microglial activation and neuroinflammation in ICH. Our finding also suggests that miR-367 might represent a potential therapeutic target for ICH. PMID- 26552594 TI - Development of 1-N-(11)C-Methyl-L- and -D-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan. AB - 1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (L) and dextrorotary (D). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy. Herein, we developed two novel radioprobes, 1-N-(11)C-methyl-L- and -D-tryptophan ((11)C-L-1MTrp and (11)C-D-1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. (11)C-L-1MTrp and (11)C-D-1MTrp were synthesized rapidly with radiochemical yields of 47 +/- 6.3% (decay-corrected, based on (11)C-CO2), a radiochemical purity of >98%, specific activity of 47-130 GBq/MUmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for (11)C-L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for (11)C-D-1MTrp, it was observed in the kidney. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Both (11)C-L-1MTrp and (11)C-D-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. PMID- 26552595 TI - Teledermatology: diagnostic reliability in 383 children. AB - BACKGROUND: There are few studies of teledermatology focused on the pediatric age group. The aim of this study was to assess the validity and reliability of store and-forward teledermatology (STD) as a diagnostic tool for pediatricians and to reduce face-to-face consultations. MATERIAL AND METHODS: A retrospective, observational study of 383 children and adolescents under 15 years of age, referred from primary care to Dermatology Department of University Hospital of La Coruna, Spain, between 2011 and 2013, using a STD consult system. RESULTS: Diagnoses concordance between pediatricians and teledermatologists was 39.2% of cases and partial concordance 16.7%. Agreement for global diagnosis was kappa = 0.78 (p = 0.000) and for specific diagnosis was kappa = 0.73 (p = 0.000). Management was concordant in 28.7% and partially concordant in 15.4%. Lower reliability was statistically associated with modification of the lesions by inappropriate treatments, incomplete clinical data or bad-quality photographic images included in the referral consultation, diagnosis of infectious diseases and rare dermatoses. The filtering percentage (as the percentage of avoided clinic-based evaluations) was 64.5%. The mean response time of the consultant dermatologists was 3.62 days. Referrals for live consultations due to poor clinical information or insufficient quality of pictures were necessary in only 10% of the cases. CONCLUSION: The degree of diagnostic accuracy for the pediatric population using STD as a diagnostic tool was similar to that achieved in adults. Its usefulness for filtering dermatologic referral was also demonstrated in the study, so it could be suitable for integration into the routine practice of pediatricians. PMID- 26552596 TI - TOGGLE: toolbox for generic NGS analyses. AB - BACKGROUND: The explosion of NGS (Next Generation Sequencing) sequence data requires a huge effort in Bioinformatics methods and analyses. The creation of dedicated, robust and reliable pipelines able to handle dozens of samples from raw FASTQ data to relevant biological data is a time-consuming task in all projects relying on NGS. To address this, we created a generic and modular toolbox for developing such pipelines. RESULTS: TOGGLE (TOolbox for Generic nGs anaLysEs) is a suite of tools able to design pipelines that manage large sets of NGS softwares and utilities. Moreover, TOGGLE offers an easy way to manipulate the various options of the different softwares through the pipelines in using a single basic configuration file, which can be changed for each assay without having to change the code itself. We also describe one implementation of TOGGLE in a complete analysis pipeline designed for SNP discovery for large sets of genomic data, ready to use in different environments (from a single machine to HPC clusters). CONCLUSION: TOGGLE speeds up the creation of robust pipelines with reliable log tracking and data flow, for a large range of analyses. Moreover, it enables Biologists to concentrate on the biological relevance of results, and change the experimental conditions easily. The whole code and test data are available at https://github.com/SouthGreenPlatform/TOGGLE . PMID- 26552597 TI - The establishment of the Triple I (Hub), an intake, information and intervention hub. AB - OBJECTIVE: An integrated intake, information and intervention service, Triple I (Hub) was evaluated against its goal to be streamlined, co-ordinated and patient focussed. The integrated service co-located six previously disparate services, often accessed by the same patients and healthcare professionals. The service was evaluated five months after implementation. METHODS: Review methods included satisfaction surveys and observations made by an external expert. RESULTS: Survey findings from 118 participants indicated positive perceptions of all aspects of the service provided by Triple I (Hub), with similar ratings provided by staff (n = 56) and clients (n = 62). The external expert reported that there was improved job satisfaction expressed by staff, and there was significant reduction in processing time of aged care referrals from 3 weeks to less than 24 hours. CONCLUSIONS: Evidence from mixed methods evaluation was used. Quantitative survey results only reported satisfaction by users, but observations provided supplementary indications for service development. PMID- 26552599 TI - Interplay Between Premature Ejaculation and Erectile Dysfunction: A Systematic Review and Meta-Analysis. AB - INTRODUCTION: The specific determinants and underlying factors linking erectile dysfunction (ED) and premature ejaculation (PE) have yet to be clearly identified. AIM: The aim of this study was to review and meta-analyze all available data regarding the link between ED and PE. METHODS: An extensive Medline Embase and Cochrane search was performed including the following words: "premature ejaculation" and "erectile dysfunction". MAIN OUTCOME MEASURES: All observational trials comparing the risk of ED in relation to PE were included. Data extraction was performed independently by two of the authors (G.R, G.C.), and conflicts resolved by the third investigator (M.M.). RESULTS: Out of 474 retrieved articles, 18 were included in the study for a total of 57,229 patients, of which 12,144 (21.2%) had PE. The presence of PE, however defined, was associated with a significant increase in ED risk (odds ratio: 3.68[2.61;5.18]; P < 0.0001). Meta-regression analysis showed that the risk of ED in PE subjects was higher in older individuals as well as in those with a lower level of education and in those who reported a stable relationship less frequently. In addition, subjects with PE and ED more often reported anxiety and depressive symptoms and a lower prevalence of organic associated morbidities, including diabetes mellitus, hypertension and dyslipidemia. All the latter associations were confirmed even after adjustment for age. Finally the risk of PE-related ED increased with the increased proportion of acquired ejaculatory problems (adj r = 0.414; P < 0.0001 after the adjustment for age). CONCLUSIONS: In conclusion, the present data showed that ED and PE are not distinctly separate entities, but should be considered from a dimensional point of view. Understanding this dimensional perspective might help sexual health care professionals in providing the most appropriate therapeutic approach to realistically increase patient related outcomes in sexual medicine. PMID- 26552598 TI - Validation of a risk prediction tool for coronary heart disease in middle-aged women. AB - BACKGROUND: Health risk appraisal tools may be useful for identifying individuals who would benefit from lifestyle changes and increased surveillance. We evaluated the validity of the Your Disease Risk tool (YDR) for estimating relative risk of coronary heart disease (CHD) among middle-aged women. METHODS: We included 55,802 women in the Nurses' Health Study who completed a mailed questionnaire about risk factors in 1994 and had no history of heart disease at that time. Participants were followed through 2004 for the occurrence of CHD. We estimated each woman's 10-year relative risk of CHD using YDR, and we compared the estimated YDR relative risk category (ranging from "very much below average" to "very much above average") to the observed relative risk for each category using logistic regression. We also examined the discriminatory accuracy of YDR using concordance statistics (c-statistics). RESULTS: There were 1165 CHD events during the 10-year follow-up period. Compared to the "about average" category, the observed age adjusted relative risk was 0.43 (95 % confidence interval: 0.33, 0.56) for the "very much below average" category and 2.48 (95 % confidence interval: 1.68, 3.67) for the "very much above average" category. The age-adjusted c-statistic for the model including the YDR relative risk category was 0.71 (95 % confidence interval: 0.69, 0.72). The model performed better in younger than older women. CONCLUSION: The YDR tool appears to have moderate validity for estimating 10-year relative risk of CHD in this population of middle-aged women. Further research should aim to improve the tool's performance and to examine its validity in other populations. PMID- 26552600 TI - Nuclear-enriched abundant transcript 1 as a diagnostic and prognostic biomarker in colorectal cancer. AB - BACKGROUND: High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; however, its' clinical significance and origin are unclear. We evaluated the diagnostic and prognostic value, and origin of whole blood NEAT1 in colorectal cancer. METHODS: Expression of NEAT1 variants, NEAT1_v1 and NEAT1_v2 were determined using real-time quantitative PCR. The diagnostic value of whole blood NEAT1 expression was evaluated in test (n = 60) and validation (n = 200) cohorts of colorectal cancer patients and normal controls (NCs). To identify the origin of NEAT1, its expression was analyzed in blood, matched primary tumor tissues, para-tumor tissues, metastatic tissues, and also immune cells from patients or NCs. Function of NEAT1 in colorectal cell lines was also assessed. The correlation of NEAT1 expression with clinical outcomes was assessed in 191 patients. RESULTS: Whole blood NEAT1 expression was significantly higher in colorectal cancer patients than in NCs. NEAT1_v1 and NEAT1_v2 expression were highly accurate in distinguishing colorectal cancer patients from NCs (area under the curve: 0.787 and 0.871, respectively). Knockdown of NEAT1_v1 in vitro could inhibit cell invasion and proliferation, while knockdown of NEAT1_v2 promoted cell growth. However, whole blood expression was not correlated with matched tissues. An elevated expression was seen in neutrophils from CRC patients. Furthermore, high expression of NEAT1_v1 was correlated with worse overall survival. In contrast, high expression of NEAT1_v2 alone was correlated with better overall survival. CONCLUSION: Whole blood NEAT1 expression is a novel diagnostic and prognostic biomarker of overall survival in colorectal cancer. Elevated NEAT1 may derive from neutrophils. PMID- 26552601 TI - We are also interested in how fathers feel: a qualitative exploration of child health center nurses' recognition of postnatal depression in fathers. AB - BACKGROUND: To become a parent is an emotionally life-changing experience. Paternal depression during the postnatal period has been associated with emotional and behavioral problems in children. The condition has predominantly been related to mothers, and the recognition of paternal postnatal depression (PND) has been paid less attention to. PND in fathers may be difficult to detect. However, nurses in pediatric services meet a lot of fathers and are in a position to detect a father who is suffering from PND. Therefore, the aim of this study was (a) to explore Child Health Center nurses' experiences of observing depression in fathers during the postnatal period; and (b) to explore hindrances of observing these fathers. METHODS: A qualitative descriptive study was conducted. Ten nurses were interviewed in 2014. A thematic data analysis was performed and data were analyzed for meaning. RESULTS: Paternal PND was experienced as being vague and difficult to detect. Experiences of fathers with such problems were limited, and it was hard to grasp the health status of the fathers, something which was further complicated when routines were lacking or when gender attitudes influenced the daily work of the nurses. CONCLUSION: This study contributes to an increased awareness of hindrances to the recognition of PND in fathers. The importance to detect all signals of paternal health status in fathers suffering from PND needs to be acknowledged. Overall, more attention needs to be paid to PND in fathers where a part of the solution for this is that they are screened just like the mothers. PMID- 26552602 TI - Transition from clinician to academic: an interview study of the experiences of UK and Australian Registered Nurses. AB - AIM: The aim of this study was to explore and compare the experiences of nurses in Australia and the UK as they moved from clinical practice into higher education institutions. BACKGROUND: When nurse education moved from hospitals into higher education institutions, the roles and career pathways of nurse educators changed. DESIGN: The design method used in this study was qualitative interview study. METHODS: Semi-structured interviews were undertaken with 14 nurse educators, seven in Australia and seven in the UK, in 2011-2012. Thematic analysis of the transcripts was undertaken and triangulated with automated content and thematic analysis by Leximancer(c) software. FINDINGS: Nurse academics in Australia and the UK voiced similar enthusiasms and concerns. These coalesced around four emergent themes: adapting to change, external pressures, teaching and progress up the academic ladder. The Leximancer(c) analysis for both sites ranked 'research' as the primary theme, linked with 'time', 'University' and 'nursing' on both sites. Respondents were aware of the importance of research to career progression in universities, but most prioritized their teaching and clinical commitments for the sake of their organizations. Most respondents were supported in their doctoral studies, but the absence of postdoctoral research teams, mentors and role models was striking. CONCLUSION: Additional support is needed to ensure that nurse academics are able to pursue research beyond doctoral level. PMID- 26552603 TI - The prevalence of anxiety among older adults in nursing homes and other residential aged care facilities: a systematic review. AB - OBJECTIVES: To synthesize and summarize the studies examining the prevalence rate of anxiety disorders and symptoms in older adults living in residential aged care. METHODS: Using the PRISMA guidelines, five electronic databases were searched using key terms and subject headings, as well as reference lists of relevant papers. The search was limited to literature published in English. Eligible studies examined the prevalence of anxiety disorders or symptoms in aged care residents aged 50+ years. RESULTS: A total of 2249 articles were identified, of which 18 studies (with a total of 5927 participants) were included in this review. The rate of overall anxiety disorders ranged from 3.2% to 20%, with the highest quality studies estimating a prevalence rate of 5% to 5.7%. Generalized anxiety disorder and specific phobias were found to be the most common anxiety disorders among aged care residents, while clinically significant anxiety symptoms were found to be more frequent (6.5% to 58.4%) than threshold disorders. CONCLUSIONS: Anxiety disorders and anxiety symptoms are common in older aged care residents. Given the paucity and overall quality of research examining anxiety within this population and the heterogeneity found in studies, further research is needed to help clarify this issue. PMID- 26552604 TI - Micro-proteomics with iterative data analysis: Proteome analysis in C. elegans at the single worm level. AB - Proteomics studies typically analyze proteins at a population level, using extracts prepared from tens of thousands to millions of cells. The resulting measurements correspond to average values across the cell population and can mask considerable variation in protein expression and function between individual cells or organisms. Here, we report the development of micro-proteomics for the analysis of Caenorhabditis elegans, a eukaryote composed of 959 somatic cells and ~1500 germ cells, measuring the worm proteome at a single organism level to a depth of ~3000 proteins. This includes detection of proteins across a wide dynamic range of expression levels (>6 orders of magnitude), including many chromatin-associated factors involved in chromosome structure and gene regulation. We apply the micro-proteomics workflow to measure the global proteome response to heat-shock in individual nematodes. This shows variation between individual animals in the magnitude of proteome response following heat-shock, including variable induction of heat-shock proteins. The micro-proteomics pipeline thus facilitates the investigation of stochastic variation in protein expression between individuals within an isogenic population of C. elegans. All data described in this study are available online via the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd), an open access, searchable database resource. PMID- 26552605 TI - Selective Enrichment of Cysteine-Containing Phosphopeptides for Subphosphoproteome Analysis. AB - Among the natural amino acids, cysteine is unique since it can form a disulfide bond through oxidation and reduction of sulfhydryl and thus plays a pervasive role in modulation of proteins activities and structures. Crosstalk between phosphorylation and other post-translational modifications has become a recurrent theme in cell signaling regulation. However, the crosstalk between the phosphorylation and the formation and reductive cleavage of disulfide bond has not been investigated so far. To facilitate the study of this crosstalk, it is important to explore the subset of phosphoproteome where phosphorylations are occurred near to cysteine in the protein sequences. In this study, we developed a straightforward sequential enrichment method by combining the thiol affinity chromatography with the immobilized titanium ion affinity chromatography to selectively enrich cysteine-containing phosphopeptides. The high specificity and high sensitivity of this method were demonstrated by analyzing the samples of Jurkat cells. This "divide and conquer" strategy by specific analysis of a subphosphoproteome enables identification of more low abundant phosphosites than the conventional global phosphoproteome approach. Interestingly, amino acid residues surrounding the identified phosphosites were enriched with buried residues (L, V, A, C) while depleted with exposed residues (D, E, R, K). Also, the phosphosites identified by this approach showed a dramatic decrease in locating in disorder regions compared to that identified by conventional global phosphoproteome. Further analysis showed that more proline directed kinases and fewer acidophilic kinases were responsible for the phosphorylation sites of this subphosphoproteome. PMID- 26552606 TI - Vitamin D deficiency and placental calcification in low-risk obstetric population: are they related? AB - OBJECTIVE: We aimed to evaluate the relationship between placental calcification and maternal and cord blood 25-hydroxyvitamin-D3 [25(OH)D] and calcium concentrations in low-risk obstetric population at term and their consequences. METHODS: Sixty non-complicated pregnant women at term admitted to maternity clinic were included in this prospective case-control study and classified into one of two groups according to grade of placental calcification by defined the Grannum classification: Group 1 (n=30), with Grade 3 placenta and Group 2 (n=30), the control group, no placental calcification noted. Baseline characteristics, maternal serum and umbilical cord 25(OH)D and calcium levels were compared between groups. RESULTS: The mean age of subjects was 26.4 +/- 5.7 years. The mean serum 25(OH)D concentration of women (n=60) was 9.3 +/- 3.4 (range 5.59 15.48) ng/mL. The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 100%. Maternal serum and cord blood calcium levels were significantly higher in Group 1 (p=0.036; p=0.037, respectively). In Group 2, maternal serum and cord blood 25(OH)D levels were higher than Group 1 (11.35 +/- 6.54 and 10.22 +/- 3.59 versus 9.6 +/- 4.2 and 9.07 +/- 2.43 ng/mL); but the difference is not statistically significant. CONCLUSIONS: Higher maternal calcium and lower 25(OH)D levels detected in patients with Grade 3 placental calcification indicated the importance of placenta on vitamin D regulation. PMID- 26552607 TI - Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells. AB - BACKGROUND: Re-activation of the transcriptional activity of the androgen receptor (AR) is an important factor mediating progression from androgen responsive to castrate-resistant prostate cancer (CRPC). However, the mechanisms regulating AR activity in CRPC remain incompletely understood. Ca(2+) /calmodulin dependent kinase kinase (CaMKK) 2 was previously shown to regulate AR activity in androgen-responsive prostate cancer cells. Our objective was to further explore the basis of this regulation in CRPC cells. METHODS: The abundance of CaMKK2 in nuclear fractions of androgen-responsive prostate cancer and CRPC, cells were determined by subcellular fractionation and Western blotting. CaMKK2 association with nuclear pore complexes (NPCs) and nucleoporins (Nups) including Nup62, were imaged by structured illumination and super-resolution fluorescence microscopy and co-immunoprecipitation, respectively. The abundance and subcellular localization of CaMKK2 and Nup62 in human clinical specimens of prostate cancer was visualized by immunohistochemistry. The role of Nups in the growth and viability of CRPC cells was assessed by RNA interference and cell counting. The involvement of CaMKK2 and Nup62 in regulating AR transcriptional activity was addressed by RNA interference, chromatin immunoprecipitation, androgen response element reporter assay, and Western blotting. RESULTS: CaMKK2 was expressed at higher levels in the nuclear fraction of CPRC C4-2 cells, than in that of androgen-responsive LNCaP cells. In C4-2 cells, CaMKK2 associated with NPCs of the nuclear envelope and physically interacted with Nup62. CaMKK2 and Nup62 demonstrated pronounced, and similar increases in both expression and perinuclear/nuclear localization in human clinical specimens of advanced prostate cancer relative to normal prostate. Knockdown of Nup62, but not of Nups, 98 or 88, reduced growth and viability of C4-2 cells. Knockdown of Nup62 produced a greater reduction of the growth and viability of C4-2 cells than of non neoplastic RWPE-1 prostatic cells. Nup62, CaMKK2, and the AR were recruited to androgen response elements of the AR target genes, prostate specific antigen, and transmembrane protease, serine 2. Knockdown of CaMKK2 and Nup62 reduced prostate specific antigen expression and AR transcriptional activity driven by androgen response elements from the prostate-specific probasin gene promoter. CONCLUSION: Nup62 and CaMKK2 are required for optimal AR transcriptional activity and a potential mechanism for AR re-activation in CRPC. PMID- 26552608 TI - Ionic Self-Assembly and Red-Phosphorescence Properties of a Charged Platinum(II) 8-Quinolinol Complex Associated with Ammonium-Based Amphiphiles. AB - A series of ionic associates based on the platinum(II) chelate of 5-sulfo-8 quinolinol, [Pt(qS)2](2-), and ammonium-based amphiphiles is described. At variance with the prototypical neutral complex Pt(q)2 (q=8-quinolinol), these dianionic fluorophores, functionalized at the periphery with sulfonate groups, can be associated by the ionic self-assembly approach with various ammonium cations, such as (H2n+1Cn)2Me2N(+) (n=12, 16, 18) or complex ammonium cations carrying three Cn carbon chains (n=12, 14, 16) and an additional amide group. Investigations of their luminescence properties in solution, in the solid state, and, when possible, in thin films revealed that the phosphorescence properties in condensed phases are directly correlated to intermolecular interactions between the luminescent [Pt(qS)2](2-) centers. Of particular interest is also the formation of a columnar liquid-crystalline phase around room temperature (between -25 and +180 degrees C), as well as the very good film-forming ability of some of these fluorophores from organic solvents. PMID- 26552609 TI - Genetic testing for monogenic diabetes using targeted next-generation sequencing in patients with maturity-onset diabetes of the young. AB - INTRODUCTION: Molecular diagnosis of monogenic diabetes mellitus is important for individualized patient care. Next-generation sequencing (NGS) enables a simultaneous analysis of multiple genes in a single test. OBJECTIVES: We aimed to assess the feasibility of using NGS for detecting mutations in a set of known monogenic diabetes gene mutations in a cohort of Polish patients with maturity onset diabetes of the young (MODY) with earlier negative Sanger sequencing results for HNF1A-MODY or GCK-MODY. PATIENTS AND METHODS: We selected a panel of 28 chromosomal genes in which mutations have been reported to cause monogenic diabetes. The MiSeq platform was used for NGS. An exon-capture assay was designed to include coding regions and splice sites. A total of 54 patients with existing negative Sanger sequencing screening results for HNF1A or GCK gene mutations were selected for the study. RESULTS: NGS results were generated for all 54 patients and 9 positive controls with previously identified HNF1A or GCK gene mutation. All selected positive controls were confirmed by NGS. Among 28 genes, mutations were detected in 16. The type of the analyzed genetic changes was described in the NGS study as high (n = 3) or moderate (n = 76). Among the detected mutations, there were 4 known GCK gene mutations that had been previously missed in Sanger sequencing. So far, Sanger sequencing allowed us to confirm 21 gene mutations detected by NGS, and segregation with diabetes in 14 pedigrees. CONCLUSIONS: Our pilot study using NGS for monogenic diabetes screening in the MODY cohort confirmed that it improves the detection of diabetes-related sequence differences. The screening with NGS should also include diabetic patients for whom Sanger-based screening for particular subtypes of MODY provided negative results. PMID- 26552610 TI - Representation of illness in Familial Amyloidotic Polyneuropathy Portuguese Association newspaper: A documental study. AB - This study explores illness representations within Familial Amyloidotic Polyneuropathy Portuguese Association newspaper . A content analysis was performed of the issue data using provisional coding related to the conceptual framework of the study. All dimensions of illness representation in Leventhal's Common Sense Model of illness cognitions and behaviors are present in the data and reflect the experience of living with this disease. Understanding how a person living with an hereditary, rare, neurodegenerative illness is important for developing community nursing interventions. In conclusion, we suggest an integration of common sense knowledge with other approaches for designing an intervention program centered on people living with an hereditary neurodegenerative illness, such as familial amyloidotic polyneuropathy. PMID- 26552611 TI - Transitional Suspensions Containing Thermosensitive Dispersant for Three Dimensional Printing. AB - Tailoring the rheology of suspensions is an essential and persistent issue form many applications, especially three-dimensional (3D) printing. Colloidal suspensions of ceramic powder (Al2O3) dispersed by a special thermosensitive dispersant (poly(acrylic acid)-poly(N-isopropylacrylamide), PAA-PNIPAM) were designed, which underwent a remarkable fluid-gel transition in response to thermal stimulus due to the phase transition of the graft chains (-PNIPAM). 3D periodic structures with a fine size of 100 MUm were assembled by 3D printing. PMID- 26552612 TI - Arsenic(V) biosorption by charred orange peel in aqueous environments. AB - Biosorption efficiency of natural orange peel (NOP) and charred orange peel (COP) was examined for the immobilization of arsenate (As(V)) in aqueous environments using batch sorption experiments. Sorption experiments were carried out as a function of pH, time, initial As(V) concentration and biosorbent dose, using NOP and COP (pretreated with sulfuric acid). Arsenate sorption was found to be maximum at pH 6.5, with higher As(V) removal percentage (98%) by COP than NOP (68%) at 4 g L(-1) optimum biosorbent dose. Sorption isotherm data exhibited a higher As(V) sorption (60.9 mg g(-1)) for COP than NOP (32.7 mg g(-1)). Langmuir model provided the best fit to describe As(V) sorption. Fourier transform infrared spectroscopy and scanning electron microscopy combined with energy dispersive X-ray spectroscopy analyses revealed that the -OH, -COOH, and -N-H surface functional groups were involved in As(V) biosorption and the meso- to micro-porous structure of COP sequestered significantly (2-times) higher As(V) than NOP, respectively. Arsenate desorption from COP was found to be lower (10%) than NOP (26%) up to the third regeneration cycle. The results highlight that this method has a great potential to produce unique 'charred' materials from the widely available biowastes, with enhanced As(V) sorption properties. PMID- 26552614 TI - Multiple facets of tightly coupled transducer-transistor structures. AB - The ever increasing demand for data processing requires different paradigms for electronics. Excellent performance capabilities such as low power and high speed in electronics can be attained through several factors including using functional materials, which sometimes acquire superior electronic properties. The transduction-based transistor switching mechanism is one such possibility, which exploits the change in electrical properties of the transducer as a function of a mechanically induced deformation. Originally developed for deformation sensors, the technique is now moving to the centre stage of the electronic industry as the basis for new transistor concepts to circumvent the gate voltage bottleneck in transistor miniaturization. In issue 37 of Nanotechnology, Chang et al show the piezoelectronic transistor (PET), which uses a fast, low-power mechanical transduction mechanism to propagate an input gate voltage signal into an output resistance modulation. The findings by Chang et al will spur further research into piezoelectric scaling, and the PET fabrication techniques needed to advance this type of device in the future. PMID- 26552613 TI - Paroxysmal Supraventricular Tachycardia With Ventriculoatrial Block and QRS Duration Shortening: What Is the Mechanism? PMID- 26552615 TI - Lung transplantation using controlled donation after circulatory death donors: Trials and tribulations. PMID- 26552616 TI - [Splenic hamartoma, severe thrombocytopenia, and macrocrania in a neonate: A case study]. AB - We report a case of splenic hamartoma associated with neonatal macrocrania diagnosed in a newborn. The diagnosis was made in the first 2 days of life upon the existence of an abdominal mass in the newborn infant. Abdominal ultrasound and abdominal computed tomography supported the diagnosis, but the histological study was inconclusive. The indication for surgery is still controversial. Through a literature review, the clinical, histological, and radiological aspects are discussed. The combination of neonatal hamartoma, thrombocytopenia, and macrocrania has never been reported. PMID- 26552617 TI - [Inflammatory pseudo-tumor of the bladder expelled through the urethral meatus in a girl]. AB - Inflammatory pseudo-tumors of the bladder are rare benign tumors that mostly arise in the differential diagnosis of sarcomas in children. The authors report an unusual case of pedunculated inflammatory pseudo-tumor of the bladder that externalized by the urethral meatus in a 13-year-old girl. The treatment consisted of a ligation-resection of the pedicle, followed by resection of the tumor. After regular follow-up for 18 months there was no tumor recurrence. PMID- 26552618 TI - [Osteoid osteoma on distal phalanx tip of second toe, without scintigraphy fixation]. AB - Osteoid osteoma is a very small painful, benign tumor, located preferentially on long bones. Cases on the phalanxes of the toes are very rare. Pain takes up nearly all the clinical presentation. Poor clinical signs and atypical location make diagnosis difficult and delayed. Sometimes, it can be confused with local infection. Various additional tests are described to help diagnosis. Technetium 99-m scintigraphy coupled with CT is the key exam with high sensitivity and morphological accuracy. We report on the case of a 10-year-old boy with an atypical location of osteoid osteoma on the distal phalanx tip of the second toe, without scintigraphy fixation and obvious nidus on X-ray and CT scan. PMID- 26552619 TI - [Heart murmurs in asymptomatic children: When should you refer?]. AB - Heart murmurs are common in children and adolescents. Although most are innocent, an isolated heart murmur in asymptomatic children may be the sole finding indicating serious heart disease. Historical elements of familial heart disease, cardiovascular symptoms and a well-conducted medical examination can identify children with an increased risk of heart disease. The distinction between an innocent heart murmur and a pathologic heart murmur is not always easy for primary care physicians because most of them have little experience with auscultation searching for congenital heart malformation. Echocardiography provides a definitive diagnosis of heart disease but is not required in case of innocent murmur. Inappropriate pediatric cardiologist and echocardiographic referral leads to useless and expensive examinations, resulting in a work overload for pediatric cardiologists. The objective of this review is to provide the keys to differentiate innocent and pathologic murmurs, and to help physicians decide on the optimal diagnostic strategy. PMID- 26552620 TI - [Child protection system: Knowledge and role of the general practitioners in Ille et-Vilaine]. AB - BACKGROUND AND AIMS: On 5 March 2007 the law concerning the child protection system was reformed. Since this date, child protection services are responsible for child abuse and neglect. Child protection services are now attempting to determine the rightful place for parents. Asking for child protection is now easier for the general practitioner (GP), who can submit a "preoccupying information (PI)" form. The aim of this study was to review GPs' knowledge on this issue 6 years after the passage of this new law. METHODS: Prospective postal investigation between 04/01/2013 and 06/01/2013. RESULTS: A total of 298 (113 women) of the 899 GPs of the Ille-et-Vilaine area in Brittany answered a few questions about their activity and their knowledge on child abuse and neglect. The sample's mean age, sex, and practice was representative of the GPs in this area. Only 25.5% of the GPs had any knowledge of this new law. The term "preoccupying information" was unfamiliar to 70.1% of the GPs and what to do with the PI was unknown to 77.2%. The GPs did not know which type of letter to send nor where to send it between legal child protection and social protection services. Only 5% of the GPs had child protection training on PI. The main problem informing the child protection services was the lack of training. Consequently, 91.9% of the GPs would like training. CONCLUSIONS: The GPs in the Ille-et-Vilaine area in Brittany are unfamiliar with the child protection updates and need special training. PMID- 26552621 TI - [Failure mode and effects analysis (FMEA) of insulin in a mother-child university affiliated health center]. AB - CONTEXT AND OBJECTIVES: Insulin is a high-alert drug. The main objective of this descriptive cross-sectional study was to evaluate the risks associated with insulin use in healthcare centers. The secondary objective was to propose corrective measures to reduce the main risks associated with the most critical failure modes in the analysis. METHODS: We conducted a failure mode and effects analysis (FMEA) in obstetrics-gynecology, neonatology and pediatrics. RESULTS: Five multidisciplinary meetings occurred in August 2013. A total of 44 out of 49 failure modes were analyzed. Nine out of 44 (20%) failure modes were deemed critical, with a criticality score ranging from 540 to 720. DISCUSSION: Following the multidisciplinary meetings, everybody agreed that an FMEA was a useful tool to identify failure modes and their relative importance. This approach identified many corrective measures. CONCLUSION: This shared experience increased awareness of safety issues with insulin in our mother-child center. This study identified the main failure modes and associated corrective measures. PMID- 26552622 TI - Percutaneous suturing technique and single-site umbilical laparoscopic repair of a Morgagni hernia: Review of three cases. AB - Morgagni hernias are uncommon, accounting for only 1-2% of all congenital diaphragmatic hernia. Minimally invasive surgery is today the gold standard treatment. We present a technique using percutaneous suturing and single-site umbilical laparoscopic repair of Morgagni hernia in three children. Recovery was uneventful in all three patients. There was no recurrence and the chest radiograph remained normal during the postoperative follow-up. The percutaneous suturing technique and single-site umbilical laparoscopic repair of a Morgagni hernia is an easy and effective alternative to standard laparoscopic repair. PMID- 26552623 TI - [Are infant formulae named "taking over from breastfeeding" useful?]. PMID- 26552624 TI - [Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia]. AB - The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers. PMID- 26552625 TI - [Thrombotic thrombocytopenic purpura in a newborn]. AB - We report the case of a newborn presenting with hemolytic anemia, thrombocytopenia, hyperbilirubinemia, and renal failure in the first hours of life. An early plasmatherapy was undertaken, with good outcome. The specific von Willebrand factor-cleaving protease activity (ADAMTS 13 for a disintegrin and metalloprotease with thrombospondin type 1 repeats) was found to be low. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura (TTP). This disease of constitutional thrombotic microangiopathy is rare. The prognosis, usually life-threatening, was completely transformed given the better understanding of the pathogenesis of the disease and therapeutic progress. PMID- 26552626 TI - [Febrile ulceronecrotic Mucha-Habermann disease]. AB - Pityriasis lichenoides et varioliformis acuta (PLEVA) is an inflammatory skin disease that is unknown to pediatricians. The ulceronecrotic febrile form is a rare and potentially lethal variant. We report the case of a 7-year-old boy with a papulovesicular eruption lasting for 4 weeks, secondarily associated with ulcers and necrotic crusts, fever, and systemic signs. After exploring infectious causes such as chickenpox, we discussed and confirmed PLEVA with histological analysis. Systemic steroids and methotrexate improved the symptoms. It is necessary to mention PLEVA in case of prolonged papulovesicular eruption. Prompt diagnosis allows appropriate treatment, although there is no consensus on therapeutic guidelines. PMID- 26552627 TI - [Scoliosis secondary to tuberculous spondylitis: A case report and discussion of diagnosis]. AB - Idiopathic scoliosis is the most common form of spinal deformity in adolescence. However, secondary causes of scoliosis should always be considered so as to provide appropriate treatment and avoid complications. Additional explorations, such as MRI, are required in the presence of atypical signs. We report a case of spinal tuberculosis, or Pott's disease, misdiagnosed as idiopathic scoliosis, and then present a discussion to help identify the warning signs during the evaluation of scoliosis that might indicate secondary scoliosis and suggest when to perform further radiologic exploration. PMID- 26552628 TI - [Recovery of Cushing syndrome revealing McCune-Albright syndrome]. AB - Cushing syndrome (CS) is a rare feature of McCune-Albright syndrome. Treatments consist of bilateral adrenalectomy followed by lifelong glucocorticoid and mineralocorticoid treatment. However, cases of spontaneous remission of CS have been reported in the literature. We report a case of McCune-Albright syndrome with CS treated with metyrapone for 30 months with prolonged remission after a 12 year follow-up. Adrenalectomy may be avoided in some cases of CS caused by McCune Albright syndrome. Metyrapone could be a good alternative to surgical treatment. PMID- 26552629 TI - [Impact of an intervention improving the food supply (excluding school meals) with educational support in middle and high schools]. AB - Within the Nutrition, Prevention, and Health Program for children and teenagers in Aquitaine, an experimental intervention was implemented in 2007-2008 in the middle and high schools in Aquitaine (southwest France). This intervention aimed to improve the eating habits of adolescents, combining actions to improve the food supply sold during recreational times (remove/limit fat and sugar products sold and promote the sale of fruits and bread) and health education actions to make adolescents aware of the concept of nutritional balance and steer their choice towards recommended products. The aim of this paper was to evaluate the impact of the intervention on the eating behavior of adolescents and the food supply sold during recreational times in middle and high schools in Aquitaine. A survey was conducted before and after the implementation of the intervention in seven middle and high schools that have implemented actions (intervention group) and eight middle and high schools that have not implemented actions (control group). In these schools, 1602 adolescents answered the survey before and 1050 after the intervention (samples were independent because of the anonymity of responses). The impact of the intervention on the dietary behavior of teenagers was modeled using logistic regression adjusted on potential confounding variables (sex, age, and educational status). In multivariate analyses, the intervention was associated with more frequent daily intake of breakfast (OR=2.63; 95% CI [1.89; 3.66]) and lower intake of morning snacks (OR=0.66; 95% CI [0.48; 0.90]), higher consumption of starchy foods (OR=1.77; 95% CI [1.30; 2.42]), bread at breakfast, morning snacks, and a light afternoon meal (OR=1.43; 95% CI [1.07; 1.90]), and the food supply sold at recreational times (OR=1.34 95% CI [1.01; 1.78]). These results show that the "Improving food supply in middle and high schools associated with educational support actions" project led to the sales of recommended foods during recreational times and improved students' eating behavior. These results encourage partners to pursue these actions in all volunteer middle and high schools. PMID- 26552630 TI - [A novel decision tree for pediatric thoracolumbar spine trauma]. PMID- 26552631 TI - [Assessment of BCG vaccine practices]. AB - Tuberculosis is a major public health problem. In France, the vaccine against tuberculosis (Bacillus Calmette-Guerin, BCG) is in decline. This decline is firstly due to changes in BGG administration that were implemented in 2006 and secondly because of new recommandations in 2007 that ended compulsory vaccination. To determine their position on this vaccine, in 2013-2014 we asked general practitioners, pediatricians, and Maternal and Infantile Protection Center physicians in the Gard and Herault departments (in Southern France) why this vaccine was not administered and their suggestions for improvement. Most of these doctors (73.9%) stated that they did not oppose this vaccination for children. They expressed concern about potential side effects, technical problems (intradermic injection, multi-dose bottles) and parents' refusal. One quarter of these physicians would have preferred that this vaccine remains compulsory and one third that this vaccine be administered in the maternity hospital. They also requested simplified criteria for patient eligibility, technical improvements (training for intradermal injection, single-dose vaccine) and more information for the public concerning this vaccination. PMID- 26552632 TI - [Neonatal mucolipidosis type II]. AB - Mucolipidosis type II (ML II, OMIM 252,500) is an autosomal recessive disorder clinically characterized by facial dysmorphia similar to Hurler syndrome and pronounced gingival hypertrophy. The disorder is caused by a defect in targeting acid hydrolases on the surface of lysosomes, which impede their entry and lead to accumulation of undigested substrates in lysosomes. The onset of the symptoms is usually in infancy, beginning in the 6th month of life. Early onset, at birth or even in utero, is a sign of severity and involves the specific dysmorphia as well as skeletal dysplasia related to hyperparathyroidism. We report on a severe neonatal form of this disorder revealed by respiratory distress with severe chest deformity. The dysmorphic syndrome, combining coarse features, pronounced gingival hypertrophy, with diffuse bone demineralization and secondary hyperparathyroidism associating significant elevation of parathyroid hormone and alkaline phosphatase with normal levels of vitamin D and calcium were characteristics of mucolipidosis type II. Recognizing this specific association of anomalies helps eliminate the differential diagnosis and establish appropriate diagnosis and care. PMID- 26552633 TI - [Colonic duplication revealed by intestinal obstruction due to fecal impaction]. AB - Colonic duplications are very rare in children. With rectal duplications, they are the rarest locations of alimentary tract duplications, most often diagnosed in the first years of life. We report an unusual case of colic duplication with fecal impaction in a 9-month-old boy revealed by intestinal obstruction. We discuss the main diagnostic and therapeutic aspects of this malformation. PMID- 26552634 TI - Vulnerability of tropical forest ecosystems and forest dependent communities to droughts. AB - Energy captured by and flowing through a forest ecosystem can be indexed by its total Net Primary Productivity (NPP). This forest NPP can also be a reflection of its sensitivity to, and its ability to adapt to, any climate change while also being harvested by humans. However detecting and identifying the vulnerability of forest and human ecosystems to climate change requires information on whether these coupled social and ecological systems are able to maintain functionality while responding to environmental variability. To better understand what parameters might be representative of environmental variability, we compiled a metadata analysis of 96 tropical forest sites. We found that three soil textural classes (i.e., sand, sandy loam and clay) had significant but different relationships between NPP and precipitation levels. Therefore, assessing the vulnerability of forests and forest dependent communities to drought was carried out using data from those sites that had one of those three soil textural classes. For example, forests growing on soil textures of sand and clay had NPP levels decreasing as precipitation levels increased, in contrast to those forest sites that had sandy loam soils where NPP levels increased. Also, forests growing on sandy loam soil textures appeared better adapted to grow at lower precipitation levels compared to the sand and clay textured soils. In fact in our tropical database the lowest precipitation level found for the sandy loam soils was 821 mm yr(-1) compared to sand at 1739 mm yr(-1) and clay at 1771 mm yr(-1). Soil texture also determined the level of NPP reached by a forest, i.e., forest growing on sandy loam and clay reached low-medium NPP levels while higher NPP levels (i.e., medium, high) were found on sand-textured soils. Intermediate precipitation levels (>1800-3000 mm yr(-1)) were needed to grow forests at the medium and high NPP levels. Low thresholds of NPP were identified at both low (~750 mm) and high precipitation (>3500 mm) levels. By combining data on the ratios of precipitation to the amount of biomass produced in a year with how much less precipitation input occurs during a drought year, it is possible to estimate whether productivity levels are sufficient to support forest growth and forest dependent communities following a drought. In this study, the ratios of annual precipitation inputs required to produce 1 Mg ha(-1) yr(-1) biomass by soil texture class varied across the three soil textural classes. By using a conservative estimate of 20% of productivity collected or harvested by people and 30% precipitation reduction level as triggering a drought, it was possible to estimate a potential loss of annual productivity due to a drought. In this study, the total NPP unavailable due to drought and harvest by forest dependent communities per year was 10.2 Mg ha(-1) yr(-1) for the sandy textured soils (64% of NPP still available), 8.4 Mg ha(-1) yr(-1) for the sandy loam textured soils (60% available) and 12.7 Mg ha(-1) yr(-1) for the clay textured soils (29% available). Forests growing on clay textured soils would be most vulnerable to drought triggered reductions in productivity so NPP levels would be inadequate to maintain ecosystem functions and would potentially cause a forest-to-savanna shift. Further, these forests would not be able to provide sufficient NPP to satisfy the requirements of forest dependent communities. By predicting the productivity responses of different tropical forest ecosystems to changes in precipitation patterns coupled with edaphic data, it could be possible to spatially identify where tropical forests are most vulnerable to climate change impacts and where mitigation efforts should be concentrated. PMID- 26552635 TI - Occlusal and MRI characterizations in systemic sclerosis patients: A prospective study from Southern Italian cohort. AB - OBJECTIVES: The aim of the present study was to assess the prevalence of temporomandibular joint (TMJ) symptoms, clinical and magnetic resonance imaging (MRI) findings in a cohort of Southern Italian patients with SSc. METHODS: Twenty seven patients with SSc (12 diffuse, 15 limited, mean age 53.9, SD+/-1.2) and 28 healthy subjects (mean age 54.8, SD+/-4.2) were enrolled in this observational cohort study. In all patients, clinical examination for assessing the presence of TMJ sounds, pain in the TMJ area, tenderness of masticatory muscles, limited mouth opening, pain assessment, MRI scan and Anamnestic and Dysfunctional Index were performed. RESULTS: The test groups reported more clinical and MRI findings of TMJ symptoms and dysfunction than control group. The frequency distributions of symptoms were significantly different (P<0.05), in the test groups for TMJ sounds, pain during mandibular movement and difficulty in the maximum mouth opening. There was also a significant decrease (P<0.001), in the test groups, in the mean of leftward, rightward laterotrusion and protrusion. Correlation analysis allowed to affirm that maximum opening leftward laterotrusion, protrusion and click were significantly correlated to Modified Rodnan Skin Score. The mean duration of disease was significantly correlated, ever in total SSc group, only for the maximum mouth opening value. CONCLUSION: This study demonstrates that TMJ involvement is common in SSc patients and is correlated with a length and involvement of disease and supports the notion that TMJ examination should be encouraged in the rheumatology setting and clinicians should provide a right pain management and patient support. PMID- 26552636 TI - Combination of nonlinear ultrasonics and guided wave tomography for imaging the micro-defects. AB - The use of guided wave tomography has become an attractive alternative to convert ultrasonic wave raw data to visualized results for quantitative signal interpretation. For more accurate life prediction and efficient management strategies for critical structural components, there is a demand of imaging micro damages in early stage. However, there is rarely investigation on guided wave tomographic imaging of micro-defects. One of the reasons for this might be that it becomes challenging to monitor tiny signal difference coefficient in a reliable manner for wave propagation in the specimens with micro-damages. Nonlinear acoustic signal whose frequency differs from that of the input signal can be found in the specimens with micro-damages. Therefore, the combination of guided wave tomography and nonlinear acoustic response induced by micro-damages could be a feasibility study for imaging micro-damages. In this paper, the nonlinear Rayleigh surface wave tomographic method is investigated to locate and size micro-corrosive defect region in an isotropic solid media. The variations of acoustic nonlinear responses of ultrasonic waves in the specimens with and without defects are used in guided wave tomographic algorithm to construct the images. The comparisons between images obtained by experimental signals and real defect region induced by hydrogen corrosion are presented in this paper. Results show that the images of defect regions with different shape, size and location are successfully obtained by this novel technique, while there is no visualized result constructed by conventional linear ultrasonic tomographic one. The present approach shows a potential for inspecting, locating and imaging micro-defects by nonlinear Rayleigh surface wave tomography. PMID- 26552637 TI - Giant balloon-like presacral schwannoma. PMID- 26552638 TI - Delayed anterior cervical screws migrating simultaneously to the lung and stomach. PMID- 26552639 TI - A rare case of complete T10-T11 fracture and dislocation with the neurologic signs of Frankel D. PMID- 26552640 TI - Aneurysmal bone cyst of the sacrum. PMID- 26552641 TI - Giant synovial sarcoma involved thoracolumbar vertebrae and paraspinal muscle. PMID- 26552642 TI - A case of atypical spinal tuberculosis mimicking metastatic tumor. PMID- 26552643 TI - BRCA2-positive spinal intramedullary ovarian metastatic disease: case report. AB - BACKGROUND CONTEXT: Ovarian cancer is the fourth leading cause of cancer death in women, but advances in treatment have led to longer survival among these patients. Tied to these advances and increased survival, however, have been new patterns of metastatic spread. PURPOSE: The authors discuss the management and surgical decision making in patients with intramedullary ovarian metastatic disease using a case illustration and relevant literature. STUDY DESIGN/SETTING: A case report was used. METHODS: The authors describe a case of a 59-year-old woman with Breast Cancer gene (BRCA) 2-positive ovarian cancer who developed progressive myelopathy from a T10 to T11 intramedullary metastatic lesion. RESULTS: The patient underwent a standard open T10-T11 laminectomy for intramedullary tumor resection. Intraoperative ultrasound was used to direct the dural opening over the lesion. After a posterior midline myelotomy, microsurgical dissection revealed the intramedullary tumor with a discolored fibrous capsule, which was carefully dissected off of the spinal tracts, and a gross total resection was achieved. Postoperative magnetic resonance imaging at 6 months demonstrated no evidence of residual or recurrent intramedullary tumor. The patient underwent adjuvant external beam radiation to the thoracic spine but succumbed to her primary disease 1 year after surgery. CONCLUSION: Although central nervous system involvement of ovarian cancer confers a poor prognosis, patients presenting with a solitary lesion and neurologic deficit may benefit from surgical resection followed by steroids and radiation therapy, especially when tissue diagnosis is necessary. PMID- 26552645 TI - Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children. AB - BACKGROUND: Congenital myasthenic syndromes consist of rare disorders resulting from mutations in genes encoding for presynaptic, synaptic, and postsynaptic proteins that are involved in the signal transmission of the neuromuscular junction. They are characterized by fatigable weakness of the skeletal muscles with symptom onset from birth to early childhood. DOK7 (downstream of tyrosine kinase 7) congenital myasthenic syndrome was previously treated successfully with ephedrine and salbutamol; however, both are unavailable in the United States. METHODS: Case report of a child with muscle weakness. RESULTS: This report describes a boy who presented only with progressive limb-girdle muscle weakness since age 2 years. The muscle biopsy with extensive studies revealed no obvious etiologies. His muscle weakness rapidly worsened, requiring a wheelchair for daily activities. Expanded neuromuscular gene panel promptly led to the diagnosis of DOK7 congenital myasthenic syndrome, and his muscle strength dramatically and persistently improved in four weeks with albuterol treatment, allowing him to walk independently. In a brief literature review, 15 patients (five treated between ages 5 and 17 years) from the Mayo Clinic with DOK7 mutations were also successfully treated with albuterol. CONCLUSION: DOK7 congenital myasthenic syndrome often presents with limb-girdle muscle weakness, which can become progressive without proper treatment. If muscle biopsy reveals no obvious etiology, an expanded neuromuscular gene panel may lead to a specific diagnosis of congenital myasthenic syndrome such as those due to DOK7 mutation. Albuterol is often used to treat bronchial asthma; however, it can also dramatically and persistently improve the muscle strength of DOK7 congenital myasthenic syndrome. PMID- 26552644 TI - Overexpression of HOXA10 promotes gastric cancer cells proliferation and HOXA10(+)/CD44(+) is potential prognostic biomarker for gastric cancer. AB - Gastric cancer (GC) is a malignant cancer with poor prognosis. This study aims to investigate the roles of homeobox A10 (HOXA10) in GC and the correlations between HOXA10/CD44 expression and GC prognosis. Based on qRT-PCR and Western Blot analyses in 50 pairs of fresh GC samples and adjacent normal samples, it is identified that HOXA10 was significantly up-regulated in GC tissues at mRNA and protein levels. Cell proliferation, migration, and invasion were enhanced in GC cells with overexpressed HOXA10, while inhibited in cells with silenced HOXA10. Through IPA software, HOXA10 was predicted to interact with CD44 via MSN, which was preliminarily confirmed by using Western Blot. Through immunohistochemistry and tissue microarray (N=264), it is found that HOXA10 expression was significantly correlated with tumor size (P=0.011) and CD44 expression (P<0.001), while CD44 expression was significantly correlated with tumor size (P<0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.001), UICC stage (P<0.001), histological differentiation (P<0.001), and HOXA10 expression (P<0.001). Additionally, the over-all survival and disease-free survival of HOXA10(+)/CD44(+) patients were dramatically decreased in comparison with that of HOXA10(+)/CD44(-), HOXA10(-)/CD44(+), or HOXA10(-)/CD44(-) patients (P<0.001), suggesting that the combinatory expression of HOXA10 and CD44 was correlated with poor GC prognosis. In conclusion, HOXA10 and CD44 might play roles in GC tumorigenesis, metastasis, and invasion. HOXA10(+)/CD44(+) expression might serve as a prognostic biomarker for GC, which needs more studies to validate. PMID- 26552647 TI - Arthroscopy and obesity. AB - Obesity is a major public health issue, as incidence is rising in all developed countries, although the proportion is lower in Europe than in the U.S. Over and above the metabolic consequences and increased risk of diabetes, cardiovascular pathology and certain forms of cancer, the present study focuses on osteoarticular risk, and in particular on pathologies manageable by arthroscopy. It also analyzes results and complications specific to arthroscopy in these indications. Meniscal and ligamentous pathologies of the knee, rotator-cuff pathology in the shoulder and tendon pathology in the elbow were not significantly elevated, although a trend emerged. In contrast, there was significant elevation of Achilles and plantar aponeurosis pathology. In terms of postoperative complications, thromboembolic risk was elevated, but there were not significantly more complications specific to arthroscopy. Finally, subjective results were comparable to those for non-obese patients. LEVEL OF EVIDENCE: Review. PMID- 26552646 TI - A Novel Parent Questionnaire for the Detection of Seizures in Children. AB - BACKGROUND: We developed a seizure questionnaire that could be administered by a trained research assistant in a two-step process, approximating the clinical diagnostic process of a pediatric epileptologist. This questionnaire was designed to study seizure prevalence in a research population of 10-year-old children at risk for epilepsy. METHODS: English-speaking parents of children 6 months to 12 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. An algorithm of parent responses rendered a 4-level ranking scale of seizure probability for events: (1) not likely, (2) indeterminate, (3) probable, (4) almost certain. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using the same four-level scale based on clinical history and examination. RESULTS: The questionnaire was completed by 150 of 177 (84.7%) enrolled parents. Seizure prevalence among participants was 38.6%. The seizure questionnaire yielded a fitted receiver operating characteristic area of 0.93 (95% confidence interval [CI], 0.89-0.97). Based on optimal sensitivity and false-positive fraction, we dichotomized the questionnaire results as consistent with seizure (levels 3 and 4) or without seizure (levels 1 and 2). Overall, findings included a 91.4% sensitivity (95% CI, 84.2%-98.6%) and an 82.6% specificity (95% CI, 74.9%-90.4%). The positive predictive value was 76.8% (95% CI, 66.9%-86.8%) and the negative predictive value was 93.8% (95% CI, 88.6% 99.1%). CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to researchers and clinicians in screening large populations of children, decreasing the time and cost of added neurological assessments. PMID- 26552648 TI - Impact of Meyerozyma guilliermondii isolated from chickens against Eimeria sp. protozoan, an in vitro analysis. AB - BACKGROUND: Avian coccidiosis is a disease caused worldwide by several species of parasite Eimeria that causes significant economic losses. This disease affects chickens development and production, that most of times is controlled with anticoccidial drugs. Although efforts have been made to address this disease, they have been made to control Eimeria sporozoites, although enteric stages are often vulnerable, however; the parasite oocyst remains a problem that must be controlled, as it has a resistant structure that facilitates dispersion. Despite some commercial products based on chemical compounds have been developed as disinfectants that destroy oocysts, the solution of the problem remains to be solved. RESULTS: In this work, we assessed in vitro anticoccidial activity of a compound(s) secreted by yeast isolated in oocysts suspension from infected chickens. The yeast was molecularly identified as Meyerozyma guilliermondii, and its anticoccidial activity against Eimeria tenella oocysts was assessed. Here, we report the damage to oocysts walls caused by M. guilliermondii culture, supernatant, supernatant extract and intracellular proteins. In all cases, a significant decreased of oocysts was observed. CONCLUSIONS: The yeast Meyerozyma guilliermondii secretes a compound with anticoccidial activity and also has a compound of protein nature that damages the resistant structure of oocyst, showing the potential of this yeast and its products as a feasible method of coccidiosis control. PMID- 26552649 TI - Sonocatalytic degradation of malachite green oxalate by a semiconductor metal oxide nanocatalyst. AB - Advanced Oxidation Process (AOP) technologies are considered to be better technique for the degradation or mineralization of many recalcitrant compounds and pollutants. In the present study heterogeneous sonocatalytic degradation of a model organic compound such as Malachite green oxalate (MGO) was carried out in the aqueous phase. Zinc oxide nanorods were prepared by precipitation method employing zinc acetates as precursors and were characterized by FT-IR, XRD, FE SEM and EDAX analysis. Degradation of MGO in the aqueous phase was studied in detail under the sonocatalytic process. Effects of pH, dye concentration, oxidant concentration, kinetics and effect of electrolytes on dye degradation were carried out to check the efficiency of the sonocatalyst. Effect of energy input on the degradation processes was also investigated. The degradation of dye molecules were monitored by UV-visible spectrophotometer and Chemical Oxygen demand (COD). The dye molecules were readily degraded at above 90% in the pH range 5.0-7.0 under ultrasound with zinc oxide nanorods. The interference of electrolytes like NaCl, KCl, Na2CO3, NaHCO3 and MgSO4 on the degradation of dye molecules were also studied on the sonocatalytic degradation of MGO. From the kinetic studies it was observed that at lower initial concentration of dye molecules the degradation efficiency was above 90%. The rate of the reaction decreased on increasing the initial dye concentrations of the dye molecules. It was observed that the complete mineralization of dye molecules was achieved without the formation of toxic by-products. The reusability of the catalyst also showed the effective degradation of the dye molecules up to five cycles without loss of the catalytic activities. PMID- 26552650 TI - A causal model for fatigue in lung cancer patients receiving chemotherapy. AB - PURPOSE: This study explored a causal model explaining fatigue in lung cancer patients currently undertaking Chemotherapy. METHOD: In this cross-sectional study, a convenience sample of 246 lung cancer patients were recruited from six Oncology centers throughout the north of Vietnam. The hypothesized model, consisting of insomnia, dyspnea, cough, anxiety, stage of disease, physical activity, nutritional status, and number of completed chemotherapy cycles, was constructed based on Piper's Integrated Fatigue Model and a review of the literature. RESULTS: All factors, except the number of completed chemotherapy cycles significantly affected fatigue. The hypothesized model explained 42.9% of fatigue variance. Dyspnea had the largest total effect on fatigue (beta = 0.397, p < 0.01), followed by cough (beta = 0.343, p < 0.01), insomnia (beta = 0.318 (p < 0.01), and anxiety (beta = 0.115, p < 0.05). However, insomnia had the greatest direct effect on fatigue. There was also interplay among those four factors in determining fatigue. Physical activity and nutrition status had small effects on fatigue (beta = - 0.148, p < 0.01 and beta = - 0.156, p < 0.01). CONCLUSION: The model fits well to explain fatigue. Having the largest direct effect on fatigue, insomnia appeared as a factor of choice for future fatigue control programs. Due to its higher direct effect on fatigue, dyspnea was recommended over cough for fatigue management. Additionally, the interactions among fatigue, dyspnea, and cough suggested that comprehensive programs, which simultaneously address these three symptoms, would be a promising approach for practitioners to consider. PMID- 26552651 TI - Erratum to: The time course of auditory and language-specific mechanisms in compensation for sibilant assimilation. PMID- 26552652 TI - The centroid paradigm: Quantifying feature-based attention in terms of attention filters. AB - This paper elaborates a recent conceptualization of feature-based attention in terms of attention filters (Drew et al., Journal of Vision, 10(10:20), 1-16, 2010) into a general purpose centroid-estimation paradigm for studying feature based attention. An attention filter is a brain process, initiated by a participant in the context of a task requiring feature-based attention, which operates broadly across space to modulate the relative effectiveness with which different features in the retinal input influence performance. This paper describes an empirical method for quantitatively measuring attention filters. The method uses a "statistical summary representation" (SSR) task in which the participant strives to mouse-click the centroid of a briefly flashed cloud composed of items of different types (e.g., dots of different luminances or sizes), weighting some types of items more strongly than others. In different attention conditions, the target weights for different item types in the centroid task are varied. The actual weights exerted on the participant's responses by different item types in any given attention condition are derived by simple linear regression. Because, on each trial, the centroid paradigm obtains information about the relative effectiveness of all the features in the display, both target and distractor features, and because the participant's response is a continuous variable in each of two dimensions (versus a simple binary choice as in most previous paradigms), it is remarkably powerful. The number of trials required to estimate an attention filter is an order of magnitude fewer than the number required to investigate much simpler concepts in typical psychophysical attention paradigms. PMID- 26552653 TI - A spectrum of intestinal injury models in neonatal mice. AB - PURPOSE: To compare the degree of necrotizing enterocolitis (NEC)-like damage under different stress conditions in neonatal mice. METHODS: 5-day-old C57BL/6 mice were assigned to: (A) breastfed and no stress factors; (B) breastfed+maternal separation (3 h daily); (C) breastfed+hypoxia+lipopolysaccharide (LPS-4 mg/kg/day); (D) hyperosmolar formula+hypoxia+LPS. Mice were killed at 9 days of life. Ileum and colon were stained for hematoxylin/eosin and blindly assessed. A scoring >=2 was considered NEC. Data were compared using one-way ANOVA and reported as median (range). RESULTS: Ileum-Mucosal injury was mild in group B (0.0-1). Hypoxia+LPS induced greater injury in group C (1.6, 1-2.5; p < 0.0001 to B) and D (2, 0.5-3.5; p < 0.0001 to B). There were no differences between group C and D (p = n.s.). There were no cases of NEC in group A or B, whereas NEC was present in 36 % group C and 68 % group D mice. Colon-a similar degree of mucosal injury was observed among group B (2, 1-3), C (1.7, 0-3) and D (1.5, 1-3; p = n.s.). NEC was present in 75 % of group B, 50 % of group C and 86 % of group D. CONCLUSION: These models establish a spectrum of intestinal injury and are useful to investigate the variability of neonatal intestinal diseases, such as NEC. PMID- 26552654 TI - Agreement of spatio-temporal gait parameters between a vertical ground reaction force decomposition algorithm and a motion capture system. AB - INTRODUCTION: A ground reaction force decomposition algorithm based on large force platform measurements has recently been developed to analyze ground reaction forces under each foot during the double support phase of gait. However, its accuracy for the measurement of the spatiotemporal gait parameters remains to be established. OBJECTIVE: The aim of the present study was to establish the agreement between the spatiotemporal gait parameters obtained using (1) a walkway (composed of six large force platforms) and the newly developed algorithm, and (2) an optoelectronic motion capture system. METHODS: Twenty healthy children and adolescents (age range: 6-17 years) and 19 healthy adults (age range: 19-51 years) participated in this study. They were asked to walk at their preferred speed and at a speed that was faster than the preferred one. Each participant performed three blocks of three trials in each of the two walking speed conditions. RESULTS: The spatiotemporal gait parameters measured with the algorithm did not differ by more than 2.5% from those obtained with the motion capture system. The limits of agreement represented between 3% and 8% of the average spatiotemporal gait parameters. Repeatability of the algorithm was slightly higher than that of the motion capture system as the coefficient of variations ranged from 2.5% to 6%, and from 1.5% to 3.5% for the algorithm and the motion capture system, respectively. CONCLUSION: The proposed algorithm provides valid and repeatable spatiotemporal gait parameter measurements and offers a promising tool for clinical gait analysis. Further studies are warranted to test the algorithm in people with impaired gait. PMID- 26552655 TI - Bonobos modify communication signals according to recipient familiarity. AB - Human and nonhuman primate communication differs in various ways. In particular, humans base communicative efforts on mutual knowledge and conventions shared between interlocutors. In this study, we experimentally tested whether bonobos (Pan paniscus), a close relative to humans, are able to take into account the familiarity, i.e. the shared interaction history, when communicating with a human partner. In five experimental conditions we found that subjects took the recipients' attentional state and their own communicative effectiveness into account by adjusting signal production accordingly. More importantly, in case of communicative failure, subjects repeated previously successful signals more often with a familiar than unfamiliar recipient, with whom they had no previous interactions, and elaborated by switching to new signals more with the unfamiliar than the familiar one, similar to what has previously been found in two year-old children. We discuss these findings in relation to the human capacity to establish common ground between interlocutors, a crucial aspect of human cooperative communication. PMID- 26552656 TI - Targeting PSMA with a Cu-64 Labeled Phosphoramidate Inhibitor for PET/CT Imaging of Variant PSMA-Expressing Xenografts in Mouse Models of Prostate Cancer. AB - PURPOSE: Prostate-specific membrane antigen (PSMA) is highly up-regulated in prostate tumor cells, providing an ideal target for imaging applications of prostate cancer. CTT-1297 (IC50 = 27 nM) is an irreversible phosphoramidate inhibitor of PSMA that has been conjugated to the CB-TE1K1P chelator for incorporation of Cu-64. The resulting positron emission tomography (PET) agent, [(64)Cu]ABN-1, was evaluated for selective uptake both in vitro and in vivo in PSMA-positive cells of varying expression levels. The focus of this study was to assess the ability of [(64)Cu]ABN-1 to detect and distinguish varying levels of PSMA in a panel of prostate tumor-bearing mouse models. PROCEDURES: CTT-1297 was conjugated to the CB-TE1K1P chelator using click chemistry and radiolabeled with Cu-64. Internalization and binding affinity of [(64)Cu]ABN-1 was evaluated in the following cell lines having varying levels of PSMA expression: LNCaP late-passage > LNCaP early passage ~ C4-2B > CWR22rv1 and PSMA-negative PC-3 cells. PET/X-ray computed tomography imaging was performed in NCr nude mice with subcutaneous tumors of the variant PSMA-expressing cell lines. RESULTS: [(64)Cu]ABN-1 demonstrated excellent uptake in PSMA-positive cells in vitro, with ~80 % internalization at 4 h for each PSMA-positive cell line with uptake (fmol/mg) correlating to PSMA expression levels. The imaging data indicated significant tumor uptake in all models. The biodistribution for late-passage LNCaP (highest PSMA expression) demonstrated the highest specific uptake of [(64)Cu]ABN-1 with tumor-to-muscle and tumor-to-blood ratios of 30 +/- 11 and 21 +/- 7, respectively, at 24 h post-injection. [(64)Cu]ABN-1 cleared through all tissues except for PSMA-positive kidneys. CONCLUSION: [(64)Cu]ABN-1 demonstrated selective uptake in PSMA-positive cells and tumors, which correlated to the level of PSMA expression. The data reported herein suggest that [(64)Cu]ABN-1 will selectively target and image variant PSMA expression and in the future will serve as a non-invasive method to follow the progression of prostate cancer in men. PMID- 26552657 TI - A Novel Imaging Biomarker Extracted from Fluorescence Microscopic Imaging of TRA 8/DR5 Oligomers Predicts TRA-8 Therapeutic Efficacy in Breast and Pancreatic Cancer Mouse Models. AB - PURPOSE: The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in human breast and pancreatic cancer mouse models. PROCEDURES: Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10(5) cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (*20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R (2)) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R (2) value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC50) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models. RESULTS: Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R (2) value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p < 0.05). The novel imaging biomarker was significantly correlated with either log10(IC50) or %TGI (p < 0.001). CONCLUSION: The imaging biomarker extracted from the cellular distribution pattern of Cy5.5 TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancer patients. PMID- 26552658 TI - Linking Syndemic Stress and Behavioral Indicators of Main Partner HIV Transmission Risk in Gay Male Couples. AB - The purpose of the current study was to examine whether syndemic stress in partnered gay men might undermine communication processes essential to the utilization of negotiated safety and other harm reduction strategies that rely on partners' HIV status disclosure. Participants included 100 gay male couples (N = 200 individuals) living in the U.S., who responded to an online survey. Participants completed measures of five syndemic factors (depression, poly-drug use, childhood sexual abuse, intimate partner violence, and sexual compulsivity). They also reported on whether condoms were used during first intercourse together and the timing of first condomless anal intercourse (CAI) relative to HIV disclosure in their relationship. Results of binary logistic regression analyses supported the hypothesis that the sum of partners' syndemic stress was negatively associated with condom use at first intercourse and with HIV disclosure prior to first CAI. Syndemic stress may contribute to HIV transmission risk between main partners in part because it accelerates the progression to CAI and interferes with communication processes central to harm reduction strategies utilized by gay men in relationships. Implications for prevention strategies and couples interventions, such as couples HIV counseling and testing, that facilitate communication skill-building, are discussed. PMID- 26552659 TI - Functional analysis of differences in transcriptional activity conferred by genetic variants in the 5' flanking region of the IL12RB2 gene. AB - Interleukin 12 receptor beta chain (IL12RB2) is a crucial regulatory factor involved in cell-mediated immune responses, and genetic variants of the gene encoding IL12RB2 are associated with susceptibility to various immune-related diseases. We previously demonstrated that haplotypes with single nucleotide polymorphisms (SNPs) in the 5' flanking region of IL12RB2, including -1035A>G (rs3762315) and -1023A>G (rs3762316), affect the expression of IL12RB2, thereby altering susceptibility to leprosy and periodontal diseases. In the present study, we identified transcription factors associated with the haplotype-specific transcriptional activity of IL12RB2 in T cells and NK cells. The -1023G polymorphism was found to create a consensus binding site for the transcription factor activating protein (AP)-1, and enzyme-linked immunosorbent assay (ELISA) based binding assays showed that these SNPs enhanced AP-1 binding to this region. In reporter assays, suppression of JunB expression using siRNA eliminated differences in the -1035G/-1023G and -1035A/-1023A regions containing IL12RB2 promoter activity in Jurkat T cells and NK3.3 cells. These results suggested that the -1035/-1023 polymorphisms created differential binding affinities for JunB that could lead to differential IL12RB2 expression. Moreover, the -1035G and 1035A alleles formed binding sites for GATA-3 and myocyte enhancer factor-2 (MEF 2), respectively. Our data indicated that in addition to JunB, the SNP at -1035/ 1023 influenced GATA-3 and MEF-2 binding affinity, potentially altering IL12RB2 transcriptional activity. These findings confirm the effects of rs3762315 and rs3762316 on IL12RB2 transcription. These genetic variants may alter cellular activation of T cells and NK cells and modify cell-mediated immune responses. PMID- 26552661 TI - Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold. AB - Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120-CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes. PMID- 26552660 TI - The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch. AB - Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes. PMID- 26552662 TI - Anti-PD-1/PD-L1 Therapy as a Promising Option for Non-Small Cell Lung Cancer: a Single arm Meta-Analysis. AB - Anti-PD-1/PD-L1 antibodies showed satisfactory efficacy in treating non-small cell lung cancer. We conducted this meta-analysis to explore the advantage subtypes and best therapeutic modalities of Anti-PD-1/PD-L1 therapy on NSCLC. A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, and the Cochrane Library. The pooled ORR, 6-month progression free survival rate (PFSR6m), and 1-year overall survival rate (OSR1y) were calculated and compared. 15 trials were included in this meta-analysis. Our analyses demonstrated the pooled ORR of 1st line and 2nd or more line anti-PD 1/PD-L1 therapy were 36.5% (21.9-51.0%) and 17.0% (14.3-19.7%), respectively. While the difference was significant (Z = 3.31, p < 0.001). The pooled ORR for non-squamous and squamous cell lung cancer were 18.5% (16.0-21.1%) and 17.9% (14.4-21.5%), respectively. The difference was not significant (Z = 0.27, p = 0.791). The pooled ORR for PD-L1 positive and negative patients were 29.6% (21.6 37.6%) and 13.5% (10.6-16.3%), respectively. The difference was significant (Z = 4.39, p < 0.001). The PFSR6m for PD-L1 positive and negative NSCLC were 50.0% (40.5-62.3%) and 27.0% (19.2-34.7%). The difference was significant (Z = 3.72, p < 0.001). The OSR1y for PD-L1 positive and negative NSCLC were 66.8% (44.8% 88.9%) and 54.0% (32.6-75.3%). The difference was not significant (Z = 0.77, p = 0.441). Anti-PD-1/PD-L1 antibody can serve as a promising treatment option for NSCLC. Patients with positive PD-L1 expression may benefit more from anti-PD-1/PD L1 therapy. 1st-line anti-PD-1/PD-L1 therapy can be chosen as the best modality. Squamous cell lung cancer also benefit from anti-PD-1/PD-L1 therapy. PMID- 26552663 TI - Contribution of EVX1 in Aggressiveness of Esophageal Squamous Cell Carcinoma. AB - Homeobox genes play an overruling role in the regional cell fate determination during development. EVX1 is known as a new target gene of BMP signaling pathway, a group of morphogens which are making the largest subset within the transformation growth factor beta (TGF-beta) superfamily. In this study, we aimed to enlighten the expression level of EVX1 in esophageal squamous cell carcinoma (ESCC) and to disclose its apparent roles in maintenance and progression of the disease. The expression level of EVX1 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients using relative comparative real-time PCR. The importance of EVX1 in development and cancer was also reviewed. EVX1 was underexpressed in 70% of tumor samples. There was a significant correlation between down-regulation of EVX1 and lymph node metastasis of tumor cells (p = 0.027). Furthermore, EVX1 underexpression was significantly correlated with depth of tumor cell invasion (P = 0.037). To the best of our knowledge, this is the first report highlighting EVX1 expression in ESCC to date. The clinicopathological relevance of EVX1 mRNA expression in ESCC targeted this gene as a new independent molecular marker for advanced tumor, which determine the characteristics and behavior of aggressive ESCC. PMID- 26552665 TI - Erratum to: An epidemiological study of paediatric motocross injuries in the United Kingdom. PMID- 26552664 TI - What maintains the high intra-follicular estradiol concentration in pre-ovulatory follicles? AB - PURPOSE: The purpose of the study was to establish the mechanism by which the estrogen concentration difference between the follicular fluid and the serum is maintained. METHODS: We used dialysis membrane with a pore size of <3 KD to characterize the estrogen-binding capacity of the follicular fluid. We performed PCR, western blot, and ELISA on luteinized granulosa cells to determine if sex hormone-binding globulin (SHBG) is produced by granulosa cells, and finally we used affinity columns and mass spectrometry to identify the estrogen-binding protein in the follicular fluid. RESULTS: We found that a significant estrogen concentration difference is maintained in a cell-free system and is lost with proteolysis of the follicular fluid proteins. Luteinized granulosa cells are likely not a source of SHBG, as we were not able to detect expression of SHBG in these cells. Perlecan was the most highly enriched follicular fluid protein in the affinity columns. CONCLUSIONS: We were able to identify perlecan as the most likely candidate for the major estrogen-binding protein in the follicular fluid. PMID- 26552666 TI - Regulatory framework for gene editing and other new breeding techniques (NBTs) in Argentina. AB - "New Breeding Techniques" (NBTs) are a group of recent innovations in plant breeding using molecular biology tools. It is becoming evident that NBTs can introduce advantageous traits for agriculture that could be commercially available very soon However, there is still a need of clarifying its regulatory status, particularly in regards to worldwide regulations on Genetically Modified Organisms (GMOs). This article reviews the meaning of the NBTs concept, performs an overall regulatory analysis of these technologies and reports the first regulation in the world that is applied to these technologies, which was issued by the Argentine Government. PMID- 26552667 TI - Climate-driven migration: an exploratory case study of Maasai health perceptions and help-seeking behaviors. AB - OBJECTIVES: By 2050, over 250 million people will be displaced from their homes by climate change. This exploratory case study examines how climate-driven migration impacts the health perceptions and help-seeking behaviors of Maasai in Tanzania. Increasing frequency and intensity of drought is killing livestock, forcing Maasai to migrate from their rural homelands to urban centers in search of ways to support their families. Little existing research investigates how this migration changes the way migrants think about health and make healthcare decisions. METHODS: This study used semi-structured qualitative interviews to explore migrant and non-migrant beliefs surrounding health and healthcare. Migrant and non-migrant participants were matched on demographic characteristics and location. RESULTS: Migrants emphasized the importance of mental health in their overall health perceptions, whereas non-migrants emphasized physical health. Although non-migrants perceived more barriers to accessing healthcare, migrant and non-migrant help-seeking behaviors were similar in that they only sought help for physical health problems, and utilized hospitals as a last option. CONCLUSIONS: These findings have implications for improving Maasai healthcare utilization, and for future research targeting other climate-driven migrant populations in the world. PMID- 26552668 TI - High efficacy of the MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis, a 20 year experience. AB - BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is an orphan disease. Chemotherapy is usually reserved to patients presenting with single system multifocal (SS-m) or multisystem (MS) disease but due to the lack of randomized studies no standard first line therapy has been defined yet. Pediatric regimens based on the vinblastine/prednisone backbone are not well tolerated in adults and probably less effective. We previously demonstrated high efficacy of the dose dense polichemotherapy regimen MACOP-B in 7 adult patients with SS-m or MS-LCH, in terms of high response rate and durable responses. Here we report an update of these data with the purpose of evaluating the long term efficacy of MACOP-B in adult LCH. METHODS: Clinical data of all adult LCH patients (n = 17) diagnosed and treated at our Institution during the past 20-year period were retrospectively reviewed. RESULTS: A total of 11 patients (6 with SS-m and 5 with MS-LCH) were treated with MACOP-B from 1995 to 2014. The overall response rate was confirmed to be 100 %, with a complete response of 73 % and a partial response rate of 27 %. Overall progression free survival was 64 %, and disease free survival after achievement of initial CR was 87 %. Overall survival rate was 82 % after 6.7 years of median follow-up. CONCLUSIONS: These data confirm high activity of MACOP-B in adult LCH, indicating that a substantial fraction of patients achieve long lasting responses and can be cured with this therapeutic approach. PMID- 26552669 TI - Total extraperitoneal approach for incarcerated obturator hernia repair. AB - PURPOSE: To compare the feasibilities and efficacies of the total extraperitoneal (TEP) technique and laparotomy for incarcerated obturator hernia repair. METHODS: All study subjects were diagnosed with incarcerated obturator hernia, preoperatively and TEP was performed as for TEP groin hernia repair. The incarcerated intestine was retracted into the peritoneal cavity with the hernia sac. The obturator foramen was then covered with a rectangular mesh (9 * 13 cm), which also covered the internal inguinal ring, Hesselbach's triangle, and the femoral ring. Non-ischemia of the incarcerated bowel was confirmed laparoscopically. In patients undergoing laparotomy, the obturator foramen was closed by continuous sutures, and no prosthesis was used. We recorded the length of hospital stay, operative time, amount of intraoperative bleeding, and postoperative complications. RESULTS: Twenty-two patients underwent obturator hernia repair in our hospital between January 2000 and December 2012, of whom 10 were treated with laparotomy and the remaining 12 via TEP. Three patients undergoing TEP were converted to laparotomy. The operation time was significantly longer in the conversion group compared with either the laparotomy or the TEP groups. There was no difference between the laparotomy and TEP groups regarding intraoperative bleeding. Patients who underwent TEP without conversion had a significantly shorter hospital stay than those who underwent laparotomy or required conversion. CONCLUSIONS: TEP provides a suitable approach for incarcerated obturator hernia repair, with favorable results regarding hospital stay. TEP is a feasible, minimally invasive technique for the repair of incarcerated obturator hernias. PMID- 26552670 TI - Method for Assaying the Lipid Kinase Phosphatidylinositol-5-phosphate 4-kinase alpha in Quantitative High-Throughput Screening (qHTS) Bioluminescent Format. AB - Lipid kinases are important regulators of a variety of cellular processes and their dysregulation causes diseases such as cancer and metabolic diseases. Distinct lipid kinases regulate the seven different phosphorylated forms of phosphatidylinositol (PtdIns). Some lipid kinases utilize long-chain lipid substrates that have limited solubility in aqueous solutions, which can lead to difficulties in developing a robust and miniaturizable biochemical assay. The ability to prepare the lipid substrate and develop assays to identify modulators of lipid kinases is important and is the focus of this methods chapter. Herein, we describe a method to prepare a DMSO-based lipid mixture that enables the 1536 well screening of the lipid kinase phosphatidylinositol-5-phosphate 4-kinase alpha (PI5P4Kalpha) utilizing the D-myo-di16-PtIns(5)P substrate in quantitative high-throughput screening (qHTS) format using the ADP-GloTM technology to couple the production of ADP to a bioluminescent readout. PMID- 26552671 TI - Assaying Ceramide Synthase Activity In Vitro and in Living Cells Using Liquid Chromatography-Mass Spectrometry. AB - Sphingolipids are one the major lipid families in eukaryotes, incorporating a diverse array of structural and signaling lipids such as sphingomyelin and gangliosides. The core lipid component for all complex sphingolipids is ceramide, a diacyl lipid consisting of a variable length fatty acid linked through an amide bond to a long chain base such as sphingosine or dihydrosphingosine. This reaction is catalyzed by a family of six ceramide synthases (CERS1-6), each of which preferentially catalyzes the synthesis of ceramides with different fatty acid chain lengths. Ceramides are themselves potent cellular and physiological signaling molecules heavily implicated in diabetes and neurodegenerative diseases, making it important for researchers to have access to sensitive and accurate assays for ceramide synthase activity. This chapter describes methods for assaying ceramide synthase activity in cell or tissue lysates, or in cultured cells (in situ), using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the readout. LC-MS/MS is a very sensitive and accurate means for assaying ceramide synthase reaction products. PMID- 26552672 TI - Fluorescent Assays for Ceramide Synthase Activity. AB - Ceramides are the central lipid metabolite of the sphingolipid family, and exert a potent influence over cell polarity, differentiation, and survival through their biophysical properties and their specific interactions with cell signaling proteins. Literature on the importance of ceramides in physiology and pathological conditions continues to grow, with ceramides having been identified as central effectors in major human pathologies such as diabetes and neurodegenerative conditions. In mammals, ceramide synthesis from a sphingoid base and a variable length fatty acid is catalyzed by a family of six ceramide synthases (CERS1-6), whose active sites exhibit differential specificity for different length fatty acids. CERS activity has traditionally been measured using radioactive substrates. More recently mass spectrometry has been used. In this chapter, we describe a fluorescent CERS assay, the results of which can be quantified using thin-layer chromatography (TLC) or high-performance liquid chromatography (HPLC). Methods for quantification with either TLC or HPLC are described. PMID- 26552674 TI - Measurement of Long-Chain Fatty Acyl-CoA Synthetase Activity. AB - Long-chain fatty acyl-CoA synthetases (ACS) are a family of essential enzymes of lipid metabolism, activating fatty acids by thioesterification with coenzyme A. Fatty acyl-CoA molecules are then readily utilized for the biosynthesis of storage and membrane lipids, or for the generation of energy by beta-oxidation. Acyl-CoAs also function as transcriptional activators, allosteric inhibitors, or precursors for inflammatory mediators. Recent work suggests that ACS enzymes may drive cellular fatty acid uptake by metabolic trapping, and may also regulate the channeling of fatty acids towards specific metabolic pathways. The implication of ACS enzymes in widespread lipid associated diseases like type 2 diabetes has rekindled interest in this protein family. Here, we describe in detail how to measure long-chain fatty acyl-CoA synthetase activity by a straightforward radiometric assay. Cell lysates are incubated with ATP, coenzyme A, Mg(2+), and radiolabeled fatty acid bound to BSA. Differential phase partitioning of fatty acids and acyl-CoAs is exploited to quantify the amount of generated acyl-CoA by scintillation counting. The high sensitivity of this assay also allows the analysis of small samples like patient biopsies. PMID- 26552673 TI - Identification of the Interactome of a Palmitoylated Membrane Protein, Phosphatidylinositol 4-Kinase Type II Alpha. AB - Phosphatidylinositol 4-kinases (PI4K) are enzymes responsible for the production of phosphatidylinositol 4-phosphates, important intermediates in several cell signaling pathways. PI4KIIalpha is the most abundant membrane-associated kinase in mammalian cells and is involved in a variety of essential cellular functions. However, the precise role(s) of PI4KIIalpha in the cell is not yet completely deciphered. Here we present an experimental protocol that uses a chemical cross linker, DSP, combined with immunoprecipitation and immunoaffinity purification to identify novel PI4KIIalpha interactors. As predicted, PI4KIIalpha participates in transient, low-affinity interactions that are stabilized by the use of DSP. Using this optimized protocol we have successfully identified actin cytoskeleton regulators-the WASH complex and RhoGEF1, as major novel interactors of PI4KIIalpha. While this chapter focuses on the PI4KIIalpha interactome, this protocol can and has been used to generate other membrane interactome networks. PMID- 26552675 TI - Qualitative and Quantitative In Vitro Analysis of Phosphatidylinositol Phosphatase Substrate Specificity. AB - Phosphoinositides compromise a family of eight membrane lipids which play important roles in many cellular signaling pathways. Signaling through phosphoinositides has been shown in a variety of cellular functions such cell proliferation, cell growth, apoptosis, and vesicle trafficking. Phospholipid phosphatases regulate cell signaling by modifying the concentration of phosphoinositides and their dephosphorylated products. To understand the role of individual lipid phosphatases in phosphoinositide turnover and functional signaling, it is crucial to determine the substrate specificity of the lipid phosphatase of interest. In this chapter we describe how the substrate specificity of an individual lipid phosphatase can be qualitatively and quantitatively measured in an in vitro radiometric assay. In addition, we specify the different expression systems and purification methods required to produce the necessary yield and functionality in order to further characterize these enzymes. The outstanding versatility and sensitivity of this assay system are yet unmatched and are therefore currently considered the standard of the field. PMID- 26552676 TI - Luciferase Reporter Assays to Assess Liver X Receptor Transcriptional Activity. AB - Luciferase reporter assays are sensitive and accurate tests that enable the analysis of regulatory sequences, the magnitude of transcriptional activity by transcription factors, and the discovery of gene regulatory elements and small molecule modulators with high levels of precision. This is made possible through detection of bioluminescence produced by luciferase-coding reporters in a wide range of cellular environments. These assays are routinely used to analyze the activity of transcription factors, including the lipid-activated liver X receptor (LXR), in response to different stimuli as well as for the identification of their ligands. In this chapter we describe in detail the assays performed to investigate LXR activity in a macrophage-like cell line (RAW 267.4). These can be easily adapted to other nuclear receptors and transcription factors. PMID- 26552677 TI - Metabolically Biotinylated Reporters for Electron Microscopic Imaging of Cytoplasmic Membrane Microdomains. AB - The protein and lipid substituents of cytoplasmic membranes are not in general homogeneously distributed across the membrane surface. Many membrane proteins, including ion channels, receptors, and other signaling molecules, exhibit a profound submicroscopic spatial organization, in some cases clustering in submicron membrane subdomains having a protein and lipid composition distinct from that of the bulk membrane. In the case of membrane-associated signaling molecules, mounting evidence indicates that their nanoscale organization, for example the colocalization of differing signaling molecules in the same membrane microdomains versus their segregation into distinct microdomain species, can significantly impact signal transduction. Biochemical membrane fractionation approaches have been used to characterize membrane subdomains of unique protein and lipid composition, including cholesterol-rich lipid raft structures. However, the intrinsically perturbing nature of fractionation methods makes the interpretation of such characterization subject to question, and indeed the existence and significance of lipid rafts remain controversial. Electron microscopic (EM) imaging of immunogold-labeled proteins in plasma membrane sheets has emerged as a powerful method for visualizing the nanoscale organization and colocalization of membrane proteins, which is not as perturbing of membrane structure as are biochemical approaches. For the purpose of imaging putative lipid raft structures, we recently developed a streamlined EM membrane sheet imaging procedure that employs a unique genetically encoded and metabolically biotinylated reporter that is targeted to membrane inner leaflet lipid rafts. We describe here the principles of this procedure and its application in the imaging of plasma membrane inner leaflet lipid rafts. PMID- 26552678 TI - Fluorescence Recovery After Photobleaching Analysis of the Diffusional Mobility of Plasma Membrane Proteins: HER3 Mobility in Breast Cancer Cell Membranes. AB - The fluorescence recovery after photobleaching (FRAP) method is a straightforward means of assessing the diffusional mobility of membrane-associated proteins that is readily performed with current confocal microscopy instrumentation. We describe here the specific application of the FRAP method in characterizing the lateral diffusion of genetically encoded green fluorescence protein (GFP)-tagged plasma membrane receptor proteins. The method is exemplified in an examination of whether the previously observed segregation of the mammalian HER3 receptor protein in discrete plasma membrane microdomains results from its physical interaction with cellular entities that restrict its mobility. Our FRAP measurements of the diffusional mobility of GFP-tagged HER3 reporters expressed in MCF7 cultured breast cancer cells showed that despite the observed segregation of HER3 receptors within plasma membrane microdomains their diffusion on the macroscopic scale is not spatially restricted. Thus, in FRAP analyses of various HER3 reporters a near-complete recovery of fluorescence after photobleaching was observed, indicating that HER3 receptors are not immobilized by long-lived physical interactions with intracellular species. An examination of HER3 proteins with varying intracellular domain sequence truncations also indicated that a proposed formation of oligomeric HER3 networks, mediated by physical interactions involving specific HER3 intracellular domain sequences, either does not occur or does not significantly reduce HER3 mobility on the macroscopic scale. PMID- 26552679 TI - Isolation and Analysis of Detergent-Resistant Membrane Fractions. AB - The hypothesis that the Golgi apparatus is capable of sorting proteins and sending them to the plasma membrane through "lipid rafts," membrane lipid domains highly enriched in glycosphingolipids, sphingomyelin, ceramide, and cholesterol, was formulated by van Meer and Simons in 1988 and came to a turning point when it was suggested that lipid rafts could be isolated thanks to their resistance to solubilization by some detergents, namely Triton X-100. An incredible number of papers have described the composition and properties of detergent-resistant membrane fractions. However, the use of this method has also raised the fiercest criticisms. In this chapter, we would like to discuss the most relevant methodological aspects related to the preparation of detergent-resistant membrane fractions, and to discuss the importance of discriminating between what is present on a cell membrane and what we can prepare from cell membranes in a laboratory tube. PMID- 26552680 TI - Detection of Isolated Mitochondria-Associated ER Membranes Using the Sigma-1 Receptor. AB - The interface between the endoplasmic reticulum (ER) and mitochondria referred to as the MAM (mitochondria-associated ER membrane) plays important roles in many physiological functions. A specific marker for this important entity of cellular structure is urgently needed. Thus, we propose in this method chapter that the membrane-bound ER chaperone sigma-1 receptor serves as an ideal marker for the MAM. We describe in detail the preparation and purification of the MAM by using the sigma-1 receptor as the marker and demonstrate the uniqueness of this marker by using a variety of cells, peripheral and neuronal. PMID- 26552681 TI - Using Surface Plasmon Resonance to Quantitatively Assess Lipid-Protein Interactions. AB - Surface Plasmon Resonance (SPR) is a quantitative, label-free method for determining molecular interactions in real time. The technology involves fixing a ligand onto a senor chip, measuring a baseline resonance angle, and flowing an analyte in bulk solution over the fixed ligand to measure the subsequent change in resonance angle. The mass of analyte bound to fixed ligand is directly proportional to the resonance angle change and the system is sensitive enough to detect as little as picomolar amounts of analyte in the bulk solution. SPR can be used to determine both the specificity of molecular interactions and the kinetics and affinity of an interaction. This technique has been especially useful in measuring the affinities of lipid-binding proteins to intact liposomes of varying lipid compositions. PMID- 26552682 TI - Analyzing Protein-Phosphoinositide Interactions with Liposome Flotation Assays. AB - Liposome flotation assays are a convenient tool to study protein-phosphoinositide interactions. Working with liposomes resembles physiological conditions more than protein-lipid overlay assays, which makes this method less prone to detect false positive interactions. However, liposome lipid composition must be well considered in order to prevent nonspecific binding of the protein through electrostatic interactions with negatively charged lipids like phosphatidylserine. In this protocol we use the PROPPIN Hsv2 (homologous with swollen vacuole phenotype 2) as an example to demonstrate the influence of liposome lipid composition on binding and show how phosphoinositide binding specificities of a protein can be characterized with this method. PMID- 26552683 TI - High-Throughput Fluorometric Assay for Membrane-Protein Interaction. AB - Membrane-protein interaction plays key roles in a wide variety of biological processes. To facilitate rapid and sensitive measurement of membrane binding of soluble proteins, we developed a fluorescence-based quantitative assay that is universally applicable to all proteins. This fluorescence-quenching assay employs fluorescence protein (FP)-tagged proteins whose fluorescence intensity is greatly decreased when they bind vesicles containing synthetic lipid dark quenchers, such as N-dimethylaminoazobenzenesulfonylphosphatidylethanolamine (dabsyl-PE). This simple assay can be performed with either a spectrofluorometer or a plate reader and optimized for different proteins with various combinations of FPs and quenching lipids. The assay allows rapid, sensitive, and accurate determination of lipid specificity and affinity for various lipid binding domains and proteins, and also high-throughput screening of small molecules that modulate membrane binding of proteins. PMID- 26552685 TI - Analysis of Sphingolipid Synthesis and Transport by Metabolic Labeling of Cultured Cells with [3H]Serine. AB - Analysis of lipid biosynthesis by radioactive precursor incorporation provides information on metabolic rates and the identity of rate-limiting enzymes and transporters. The biosynthesis of sphingolipids in cultured cells is initiated in the endoplasmic reticulum (ER) by the formation of a sphingoid base from serine and palmitoyl-CoA. N-acylation of the sphingoid base produces ceramide, which is transported to the Golgi apparatus where phosphocholine or carbohydrate headgroups are added to form sphingomyelin (SM) and complex glycosphingolipids (GSLs), respectively. Herein is described a protocol to measure ceramide and SM biosynthesis in cultured cells based on [(3)H]serine incorporation at the first step in the pathway. The method can be used to assay the effect of pharmacological and genetic manipulations on ceramide synthesis and transport to the Golgi apparatus. PMID- 26552684 TI - Guidelines for the Use of Protein Domains in Acidic Phospholipid Imaging. AB - Acidic phospholipids are minor membrane lipids but critically important for signaling events. The main acidic phospholipids are phosphatidylinositol phosphates (PIPs also known as phosphoinositides), phosphatidylserine (PS), and phosphatidic acid (PA). Acidic phospholipids are precursors of second messengers of key signaling cascades or are second messengers themselves. They regulate the localization and activation of many proteins, and are involved in virtually all membrane trafficking events. As such, it is crucial to understand the subcellular localization and dynamics of each of these lipids within the cell. Over the years, several techniques have emerged in either fixed or live cells to analyze the subcellular localization and dynamics of acidic phospholipids. In this chapter, we review one of them: the use of genetically encoded biosensors that are based on the expression of specific lipid binding domains (LBDs) fused to fluorescent proteins. We discuss how to design such sensors, including the criteria for selecting the lipid binding domains of interest and to validate them. We also emphasize the care that must be taken during data analysis as well as the main limitations and advantages of this approach. PMID- 26552686 TI - Determination and Characterization of Tetraspanin-Associated Phosphoinositide-4 Kinases in Primary and Neoplastic Liver Cells. AB - Accumulating evidence implicates phosphoinositide 4-phosphate as a regulatory molecule in its own right recruiting specific effector proteins to cellular membranes. Here, we describe biochemical and immunocytochemical methods to evaluate tetraspanin-associated phosphoinositide-4 kinases activity in primary human hepatic stellate cells (hHSC) and neoplastic hepatoblastoma cells. PMID- 26552687 TI - Analysis of the Phosphoinositide Composition of Subcellular Membrane Fractions. AB - Phosphoinositides play critical roles in the transduction of extracellular signals through the plasma membrane and also in endomembrane events important for vesicle trafficking and organelle function (Di Paolo and De Camilli, Nature 443(7112):651-657, 2006). The response triggered by these lipids is heavily dependent on the microenvironment in which they are found. HPLC analysis of labeled phosphoinositides allows quantification of the levels of each phosphoinositide species relative to their precursor, phosphatidylinositol. When combined with subcellular fractionation techniques, this strategy allows measurement of the relative phosphoinositide composition of each membrane fraction or organelle and determination of the microenvironment in which each species is enriched. Here, we describe the steps to separate and quantify total or localized phosphoinositides from cultured cells. PMID- 26552688 TI - Single-Molecule Imaging of Signal Transduction via GPI-Anchored Receptors. AB - Lipid rafts have been drawing extensive attention as a signaling platform. To investigate molecular interactions in lipid rafts, we often need to observe molecules in the plasma membranes of living cells because chemical fixation and subsequent immunostaining with divalent or multivalent antibodies may change the location of the target molecules. In this chapter, we describe how to examine dynamics of raft-associated glycosylphosphatidylinositol (GPI)-anchored receptors and interactions of the receptors with downstream signaling molecules by single particle tracking or single-molecule imaging techniques. PMID- 26552689 TI - Measuring Phosphatidylinositol Generation on Biological Membranes. AB - Phosphatidylinositol (PI) is a phospholipid molecule required for the generation of seven different phosphoinositide lipids which have a diverse range of signaling and trafficking functions. The precise mechanism of phosphatidylinositol supply during receptor activated signaling and the cellular compartmentation of the synthetic process are still incompletely understood and remain controversial despite several decades of research in this area. The synthesis of phosphatidylinositol requires the activity of an enzyme called phosphatidylinositol synthase, also known as CDIPT, which catalyzes a reversible headgroup exchange reaction on its substrate liponucleotide CDP-diacylglycerol resulting in the incorporation of inositol to generate phosphatidylinositol and the release of CMP. This protocol describes a method for locating PI synthase activity in isolated, intact biological membranes and vesicles. PMID- 26552690 TI - Assay for CDP-Diacylglycerol Generation by CDS in Membrane Fractions. AB - CDP-DAG is a liponucleotide formed by the condensation of CTP with the phospholipid phosphatidic acid in a reaction catalyzed by CDP-DAG synthase (CDS). CDP-DAG is required for the synthesis of phosphatidylinositol; the parent molecule whence all seven phosphoinositides including the signaling molecules PI4P, PI(4,5)P2, and PI(3,4,5)P3 are derived. This protocol describes a highly sensitive radiometric assay to detect the generation of CDP-DAG on isolated biological membrane fractions. PMID- 26552691 TI - Ketamine for prehospital trauma analgesia in a low-resource rural trauma system: a retrospective comparative study of ketamine and opioid analgesia in a ten-year cohort in Iraq. AB - BACKGROUND: Opioid analgesics are used in most trauma systems, and only a few studies report on the use of ketamine for prehospital analgesia. In a low-cost rural trauma system in Iraq paramedics have been using prehospital ketamine analgesia for ten years. This study aims to evaluate the effects of prehospital analgesia on physiologic trauma severity indicators and compare the effect of ketamine and pentazocine on those indicators. METHODS: The investigation was conducted as a retrospective cohort study with parallel group design. Three subsamples of trauma patients were compared: no analgesia (n = 275), pentazocine analgesia (n = 888), and ketamine analgesia (n = 713). Physiologic severity scores were calculated based on rated values for respiratory rate, blood pressure, and consciousness. The associations between outcomes and explanatory variables were assessed using a generalized linear model. RESULTS: Paramedic administration of analgesia was associated with a better physiologic severity score (PSS) outcome (p = 0.01). In the two subsamples receiving analgesia significantly better outcomes were observed for respiration (p < 0.0001) and systolic blood pressure (p < 0.0001). In patients with Injury Severity Score >8 ketamine was associated with a significantly better effect on the systolic blood pressure compared to opioid analgesia (p = 0.03). CONCLUSION: Prehospital analgesia for trauma victims improves physiologic severity indicators in a low resource trauma system. Compared to pentazocine, ketamine was associated with improved blood pressure for patients with serious injuries. In a low-resource setting, ketamine seems to be a good choice for prehospital analgesia in trauma patients. PMID- 26552692 TI - Roseomonas elaeocarpi sp. nov., isolated from olive (Elaeocarpus hygrophilus Kurz.) phyllosphere. AB - An aerobic, Gram-stain-negative, coccobacillus-shaped, non-endospore-forming, pink-pigmented bacterium, designated PN2T, was isolated from an olive leaf. The strain grew at 15-35 degrees C with an optimum temperature for growth at 30 degrees C, and at pH 5.0-7.5 with an optimum pH for growth at 6.0. Growth was observed in the presence of up to 1.02 % (w/v) NaCl. The major fatty acids were C19 : 0 cyclo omega8c, C16 : 0 and C18 : 1omega7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, unknown aminolipids, an unknown phospholipid and an unknown lipid. The respiratory quinone was ubiquinone-10. The DNA G+C content of strain PN2T was 70.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PN2T was closely related to members of the genus Roseomonas and shared highest similarity with Roseomonas mucosa ATCC BAA-692T (96.5 %), Roseomonas gilardii subsp. gilardii ATCC 49956T (96.2 %) and Roseomonas gilardii subsp. rosea ATCC BAA-691T (96.2 %). Furthermore, the DNA-DNA relatedness value between strain PN2T and the closest related species R. mucosa ATCC BAA-692T was 27 %. These data allowed the phenotypic and genotypic differentiation of strain PN2T from its closest phylogenetic neighbour (R. mucosa ATCC BAA-692T). Based on phenotypic and genotypic characteristics, strain PN2T is classified as representing a novel species of the genus Roseomonas for which the name Roseomonas elaeocarpi sp. nov. is proposed. The type strain is PN2T ( = BCC 44864T = NBRC 107871T). PMID- 26552693 TI - Blood alcohol in victims of sudden cardiac death in northern Finland. AB - AIMS: Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. The present study was aimed to assess the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event. METHODS AND RESULTS: Victims of unexpected SCD [n = 2363, age 61 +/- 12 years, males 1940 (82%)] included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico legal autopsy, and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients who were admitted to a hospital due to an acute myocardial infarction [n = 128, age 63 +/- 10 years, males 100 (78%)] served as controls. Based on autopsy findings, 1691 of these victims had ischaemic heart disease (IHD) and were included in the present analysis. A total of 646 (38%) SCD victims with IHD had a blood ethanol concentration above 00/00. Of these victims with blood alcohol test positive, 41% (n = 264) had blood ethanol concentration >=1.50/00 and 56% (n = 362) >=10/00. Male SCD victims had more frequently alcohol in blood than the females (40 vs. 27%, P < 0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n = 88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing. CONCLUSION: Almost 4 of 10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the northern Finland autopsy population. PMID- 26552694 TI - Lesions with unclear malignant potential (B3) after minimally invasive breast biopsy: evaluation of vacuum biopsies performed in Switzerland and recommended further management. AB - BACKGROUND: Histopathological B3 lesions after minimal invasive breast biopsy (VABB) are a particular challenge for the clinician, as there are currently no binding recommendations regarding the subsequent procedure. PURPOSE: To analyze all B3 lesions, diagnosed at VABB and captured in the national central Swiss MIBB database and to provide a data basis for further management in this subgroup of patients. MATERIAL AND METHODS: All 9,153 stereotactically, sonographically, or magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsies, performed in Switzerland between 2009 and 2011, captured in a central database, were evaluated. The rate of B3 lesions and the definitive pathological findings in patients who underwent surgical resection were analyzed. RESULTS: The B3 rate was 17.0% (1532 of 9000 biopsies with B classification). Among the 521 lesions with a definitive postoperative diagnosis, the malignancy rate (invasive carcinoma or DCIS) was 21.5%. In patients with atypical ductal hyperplasia, papillary lesions, flat epithelial atypia, lobular neoplasia, and radial scar diagnosed by VABB, the malignancy rates were 25.9%, 3.1%, 18.3%, 26.4%, and 11.1%, respectively. CONCLUSION: B3 lesions, comprising 17%, of all analyzed biopsies, were common and the proportion of malignancies in those lesions undergoing subsequent surgical excision was high (21.5%). PMID- 26552696 TI - Para-occupational exposures to asbestos: lessons learned from Casale Monferrato, Italy. PMID- 26552695 TI - Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence. AB - The burden of disabling musculoskeletal pain and injuries (musculoskeletal disorders, MSDs) arising from work-related causes in many workplaces remains substantial. There is little consensus on the most appropriate interventions for MSDs. Our objective was to update a systematic review of workplace-based interventions for preventing and managing upper extremity MSD (UEMSD). We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis. 6 electronic databases were searched (January 2008 until April 2013 inclusive) yielding 9909 non-duplicate references. 26 high-quality and medium-quality studies relevant to our research question were combined with 35 from the original review to synthesise the evidence on 30 different intervention categories. There was strong evidence for one intervention category, resistance training, leading to the recommendation: Implementing a workplace-based resistance training exercise programme can help prevent and manage UEMSD and symptoms. The synthesis also revealed moderate evidence for stretching programmes, mouse use feedback and forearm supports in preventing UEMSD or symptoms. There was also moderate evidence for no benefit for EMG biofeedback, job stress management training, and office workstation adjustment for UEMSD and symptoms. Messages are proposed for both these and other intervention categories. PMID- 26552697 TI - Structural basis for collagen recognition by the immune receptor OSCAR. AB - The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 uM measured in solution, but shows a higher affinity (KD 1.5 MUM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2. PMID- 26552699 TI - Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers. AB - Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genome wide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression. PMID- 26552698 TI - High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion. AB - The ability of von Willebrand factor (VWF) to initiate platelet adhesion depends on the number of monomers in individual VWF multimers and on the self-association of individual VWF multimers into larger structures. VWF self-association is accelerated by shear stress. We observed that VWF self-association occurs during adsorption of VWF onto surfaces, assembly of secreted VWF into hyperadhesive VWF strings on the endothelial surface, and incorporation of fluid-phase VWF into VWF fibers. VWF adsorption under static conditions increased with increased VWF purity and was prevented by a component of plasma. We identified that component as high-density lipoprotein (HDL) and its major apolipoprotein ApoA-I. HDL and ApoA-I also prevented VWF on the endothelium from self-associating into longer strands and inhibited the attachment of fluid-phase VWF onto vessel wall strands. Platelet adhesion to VWF fibers was reduced in proportion to the reduction in self-associated VWF. In a mouse model of thrombotic microangiopathy, HDL also largely prevented the thrombocytopenia induced by injection of high doses of human VWF. Finally, a potential role for ApoA-I in microvascular occlusion associated with thrombotic thrombocytopenic purpura and sepsis was revealed by the inverse relationship between the concentration of ApoA-I and that of hyperadhesive VWF. These results suggest that interference with VWF self association would be a new approach to treating thrombotic disorders. PMID- 26552700 TI - Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. AB - The histone acetyltransferases CBP/p300 are involved in recurrent leukemia associated chromosomal translocations and are key regulators of cell growth. Therefore, efforts to generate inhibitors of CBP/p300 are of clinical value. We developed a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, I-CBP112, that targets the CBP/p300 bromodomains. Exposure of human and mouse leukemic cell lines to I-CBP112 resulted in substantially impaired colony formation and induced cellular differentiation without significant cytotoxicity. I-CBP112 significantly reduced the leukemia-initiating potential of MLL-AF9(+) acute myeloid leukemia cells in a dose-dependent manner in vitro and in vivo. Interestingly, I-CBP112 increased the cytotoxic activity of BET bromodomain inhibitor JQ1 as well as doxorubicin. Collectively, we report the development and preclinical evaluation of a novel, potent inhibitor targeting CBP/p300 bromodomains that impairs aberrant self-renewal of leukemic cells. The synergistic effects of I-CBP112 and current standard therapy (doxorubicin) as well as emerging treatment strategies (BET inhibition) provide new opportunities for combinatorial treatment of leukemia and potentially other cancers. PMID- 26552701 TI - Assembly and Release of Hepatitis B Virus. AB - The hepatitis B virus (HBV) core protein is a dynamic and versatile protein that directs many viral processes. During capsid assembly, core protein allosteric changes ensure efficient formation of a stable capsid that assembles while packaging viral RNA-polymerase complex. Reverse transcription of the RNA genome as well as transport of the capsid to multiple cellular compartments are directed by dynamic phosphorylation and structural changes of core protein. Subsequently, interactions of the capsid with the surface proteins and/or host proteins trigger envelopment and release of the viral capsids or the transport to the nucleus. Held together by many weak protein-protein interactions, the viral capsid is an extraordinary metastable machine that is stable enough to persist in the cellular and extracellular environment but dissociates to allow release of the viral genome at the right time during infection. PMID- 26552703 TI - Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion. AB - Mitochondria are vital and highly dynamic organelles that continuously fuse and divide to maintain mitochondrial quality. Mitochondrial dysfunction impairs cellular integrity and is known to be associated with various human diseases. However, the mechanism by which the quality of mitochondria is maintained remains largely unexplored. Here we show that impaired proteasome function recovers the growth of yeast cells lacking Fzo1, a pivotal protein for mitochondrial fusion. Decreased proteasome activity increased the mitochondrial oxidoreductase protein Mia40 and the ratio of the short isoform of mitochondrial intermembrane protein Mgm1 (s-Mgm1) to the long isoform (l-Mgm1). The increase in Mia40 restored mitochondrial membrane potential, while the increase in the s-Mgm1/l-Mgm1 ratio promoted mitochondrial fusion in an Fzo1-independent manner. Our findings demonstrate a new pathway for mitochondrial quality control that is induced by proteasome impairment. PMID- 26552702 TI - The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility. AB - HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Mullerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility. PMID- 26552704 TI - Filamin A Expression Negatively Regulates Sphingosine-1-Phosphate-Induced NF kappaB Activation in Melanoma Cells by Inhibition of Akt Signaling. AB - Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that regulates many processes in inflammation and cancer. S1P is a ligand for five G-protein-coupled receptors, S1PR1 to -5, and also has important intracellular actions. Previously, we showed that intracellular S1P is involved in tumor necrosis factor alpha (TNF) induced NF-kappaB activation in melanoma cell lines that express filamin A (FLNA). Here, we show that extracellular S1P activates NF-kappaB only in melanoma cells that lack FLNA. In these cells, S1P, but not TNF, promotes IkappaB kinase (IKK) and p65 phosphorylation, IkappaBalpha degradation, p65 nuclear translocation, and NF-kappaB reporter activity. NF-kappaB activation induced by S1P was mediated via S1PR1 and S1PR2. Exogenous S1P enhanced the phosphorylation of protein kinase Cdelta (PKCdelta), and its downregulation reduced S1P-induced the phosphorylation of IKK and p65. In addition, silencing of Bcl10 also inhibited S1P-induced IKK phosphorylation. Surprisingly, S1P reduced Akt activation in melanoma cells that express FLNA, whereas in the absence of FLNA, high phosphorylation levels of Akt were maintained, enabling S1P-mediated NF kappaB signaling. In accord, inhibition of Akt suppressed S1P-mediated IKK and p65 phosphorylation and degradation of IkappaBalpha. Hence, these results support a negative role of FLNA in S1P-mediated NF-kappaB activation in melanoma cells through modulation of Akt. PMID- 26552705 TI - A p38 Mitogen-Activated Protein Kinase-Regulated Myocyte Enhancer Factor 2-beta Catenin Interaction Enhances Canonical Wnt Signaling. AB - Canonical Wnt/beta-catenin signaling plays a major role in various biological contexts, such as embryonic development, cell proliferation, and cancer progression. Previously, a connection between p38 mitogen-activated protein kinase (MAPK) signaling and Wnt-mediated activation of beta-catenin was implied but poorly understood. In the present study, we investigated potential cross talk between p38 MAPK and Wnt/beta-catenin signaling. Here we show that a loss of p38 MAPK alpha/beta function reduces beta-catenin nuclear accumulation in Wnt3a stimulated primary vascular smooth muscle cells (VSMCs). Conversely, active p38 MAPK signaling increases beta-catenin nuclear localization and target gene activity in multiple cell types. Furthermore, the effect of p38 MAPK alpha/beta on beta-catenin activity is mediated through phosphorylation of a key p38 MAPK target, myocyte enhancer factor 2 (MEF2). Here we report a p38 MAPK-mediated, phosphorylation-dependent interaction between MEF2 and beta-catenin in multiple cell types and primary VSMCs that results in (i) increased beta-catenin nuclear retention, which is reversed by small interfering RNA (siRNA)-mediated MEF2 gene silencing; (ii) increased activation of MEF2 and Wnt/beta-catenin target genes; and (iii) increased Wnt-stimulated cell proliferation. These observations provide mechanistic insight into a fundamental level of cross talk between p38 MAPK/MEF2 signaling and canonical Wnt signaling. PMID- 26552706 TI - DNAM-1 controls NK cell activation via an ITT-like motif. AB - DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell-mediated elimination of transformed and virus infected cells. It also has a key role in expansion and maintenance of virus specific memory NK cells. Herein, the mechanism by which DNAM-1 controls NK cell mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3' kinase, and phospholipase C-gamma1. It also promoted activation of kinases Erk and Akt, and calcium fluxes. Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. DNAM-1 signaling was also required to enhance cytotoxicity, by increasing actin polymerization and granule polarization. We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)-like motif coupling DNAM-1 to Grb2 and other downstream effectors. PMID- 26552707 TI - CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow. AB - Hematopoietic stem cells (HSCs) depend on the bone marrow (BM) niche for their maintenance, proliferation, and differentiation. The BM niche is composed of nonhematopoietic and mature hematopoietic cells, including megakaryocytes (Mks). Thrombopoietin (Thpo) is a crucial cytokine produced by BM niche cells. However, the cellular source of Thpo, upon which HSCs primarily depend, is unclear. Moreover, no specific molecular pathway for the regulation of Thpo production in the BM has been identified. Here, we demonstrate that the membrane protein C-type lectin-like receptor-2 (CLEC-2) mediates the production of Thpo and other factors in Mks. Mice conditionally deleted for CLEC-2 in Mks (Clec2(MkDelta/Delta)) produced lower levels of Thpo in Mks. CLEC-2-deficient Mks showed down-regulation of CLEC-2-related signaling molecules Syk, Lcp2, and Plcg2. Knockdown of these molecules in cultured Mks decreased expression of Thpo. Clec2(MkDelta/Delta) mice exhibited reduced BM HSC quiescence and repopulation potential, along with extramedullary hematopoiesis. The low level of Thpo production may account for the decline in HSC potential in Clec2(MkDelta/Delta) mice, as administration of recombinant Thpo to Clec2(MkDelta/Delta) mice restored stem cell potential. Our study identifies CLEC-2 signaling as a novel molecular mechanism mediating the production of Thpo and other factors for the maintenance of HSCs. PMID- 26552709 TI - Effective High-Level Disinfection of Cystoscopes: Is Perfusion of Channels Required? PMID- 26552708 TI - Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis. AB - Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1beta) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis. PMID- 26552711 TI - Liquid-liquid phase separation of freely falling undercooled ternary Fe-Cu-Sn alloy. AB - The active modulation and control of the liquid phase separation for high temperature metallic systems are still challenging the development of advanced immiscible alloys. Here we present an attempt to manipulate the dynamic process of liquid-liquid phase separation for ternary Fe47.5Cu47.5Sn5 alloy. It was firstly dispersed into numerous droplets with 66 ~ 810 MUm diameters and then highly undercooled and rapidly solidified under the containerless microgravity condition inside drop tube. 3-D phase field simulation was performed to explore the kinetic evolution of liquid phase separation. Through regulating the combined effects of undercooling level, phase separation time and Marangoni migration, three types of separation patterns were yielded: monotectic cell, core shell and dispersive structures. The two-layer core-shell morphology proved to be the most stable separation configuration owing to its lowest chemical potential. Whereas the monotectic cell and dispersive microstructures were both thermodynamically metastable transition states because of their highly active energy. The Sn solute partition profiles of Fe-rich core and Cu-rich shell in core-shell structures varied only slightly with cooling rate. PMID- 26552712 TI - BH3 mimetic ABT-737 induces apoptosis in CD34+ acute myeloid leukemia cells and shows synergistic effect with conventional chemotherapeutic drugs. AB - AIMS: Acute myeloid leukemia (AML) is an immunophenotypically heterogenous malignant disease. The early immature CD34+ AML cell subpopulation is frequently impervious to intensive chemotherapy, making them largely responsible for relapse of AML. CD34+ AML cells have higher level of Bcl-2 protein expression than the CD34- subpopulation. As such, development of drugs that specifically target the Bcl-2 may have the potential to eliminate immature CD34+ AML progenitor cells and provide therapeutic benefit. In this work, we made an attempt to investigate the cytotoxic effect of a novel Bcl-2 family inhibitor, ABT-737, on CD34+ AML cell lines (KG1a and Kasumi-1) as well as CD34+ primary AML cells. METHODS: Primary human CD34+ cells were isolated from bone marrow mononuclear cells using CD34 MicroBead kit. The growth inhibitory effect was measured by cell counting kit-8. Apoptosis was analyzed by annexin V/PI assays. Protein expression was determined by Western blotting analysis. RESULTS: Inhibition of Bcl-2 by ABT-737 effectively inhibited growth and induced apoptosis in CD34+ AML cell lines and CD34+ primary AML cells without affecting CD34+ normal hematopoietic cells. Furthermore, Western blot analysis showed that ABT-737 induced apoptosis associated with caspase-3 activation and poly ADP-ribose polymerase (PARP) degradation. Finally, ABT-737 synergistically enhanced the cytotoxic effect of cytarabine and daunorubicin in CD34+ AML cells. CONCLUSION: Taken together, these findings indicate that ABT-737 may offer as a promising molecular targeting agent in CD34+ AML. PMID- 26552713 TI - Evaluation of the impact of multivalent metal ions on the permeation behavior of Dolutegravir sodium. AB - Interactions between active pharmaceutical ingredients (APIs) and polyvalent cations are an important factor within drug absorption in the gastrointestinal tract. Dolutegravir sodium, as a second-generation integrase stand transfer inhibitor for the treatment of HIV was investigated regarding chelation with Al(3+), Ca(2+), Fe(3+), Mg(2+ )and Zn(2+) ions at three different molar ratios. Furthermore, the influence of drug-ion chelates on the permeability of the drug across two intestinal membrane models was analyzed. For this purpose, Caco-2 monolayer model and Ussing chamber technique utilizing freshly excited rat intestinal mucosa were chosen and a buffer system without additional Mg(2+) and Ca(2+) ions was tested regarding cell detachment. The addition of polyvalent cations in an equal molar ratio to the drug solution decreased the dissolved drug by at least 11%. An increased multivalent cation concentration in a ratio of 1:10 afforded an API drop in the solution of at least 88% with the exception of Mg(2+). In particular, Dolutegravir sodium was chelated with iron ions to nearly 100%. Overall, the higher the amount of metal ions in the solution, the lower was the detected amount of the drug. The permeation experiments across the Caco-2 monolayer and the rat intestinal mucosa pointed out that the addition of AlCl3, CaCl2 and ZnCl2 in a molar ratio of 10:1 to the drug led to significantly decreased drug permeation. According to these results the co-administration of Al(3+), Ca(2+ )or Zn(2+ )as well as of supplementary medications containing these polyvalent ions is in case of oral Dolutegravir delivery not recommended. PMID- 26552714 TI - Prediction of nested complementary pattern in argon dielectric-barrier discharge at atmospheric pressure. AB - A two-dimensional self-consistent fluid model was employed to investigate the spatiotemporal nonlinear behavior in an argon glow-like/Townsend-like dielectric barrier discharge (DBD) at atmospheric pressure. The discharge is characterized by a major current pulse with a residual one ahead per half cycle of the external voltage. The two current pulses are operated in glow mode, but with Townsend mode between them. Contrasting spatial discharge structures are complementarily presented not only at two current pulses in the same half cycle but also during the discharge in the two adjacent-half cycles, resulting in the formation of a unique nested complementary pattern each cycle. This peculiar behavior mainly lies in the fact that sufficient charged particles are trapped in the gas gap due to the last discharge and able to dominate the subsequent discharge through the "spatial memory effect". The charge transport regime reveals that this nested complementary pattern is presented only in a limited range of driving frequency. PMID- 26552715 TI - Standardized weaning of infants <32 weeks of gestation from continuous positive airway pressure - a feasibility study. AB - The practice of weaning premature infants from continuous positive airway pressure (CPAP) varies considerably and is usually performed without written standards. In this study, the feasibility of a standardized weaning approach was evaluated. In a quasi-experimental design, data from a prospective, post intervention cohort (n=41) were compared to data from a pre-intervention cohort (n=36). Standardized weaning was feasible but no significant differences in short term respiratory outcomes were observed. Weaning from CPAP was achieved at 32.1 +/- 1.6 (post-intervention) versus 32.5 +/- 2.3 weeks (pre-intervention) postmenstrual age. More rigorous, large-scale clinical trials are necessary before firm recommendations on distinct weaning regimens can be made. PMID- 26552716 TI - The use of mobile smart devices and medical apps in the family practice setting. AB - RATIONALE, AIMS AND OBJECTIVES: In this study smartphones/tablet PCs and medical application utilization by family physicians and factors concerning the acceptance of medical application in family practice setting have been studied. METHODS: One hundred seventy-six participants voluntarily agreed to fill out a 27 item questionnaire. Data were analysed with descriptive statistics and eight items (acceptability of utilization of applications) revealed Cronbach's alpha of 0.965 and the factor analysis showed one factor explaining 80.6% of total variance. RESULTS: The mean age of respondents was 35.7 [standard deviation (SD) = 8.12; min-max = 24-52], 79 were male (45.9%) and 88 female (51.2%), 56 (32.5%) were single and 113 (65.7%) married, and the mean experience duration as a physician was 11.1 years (SD = 11.1; min-max = 1-28). One hundred sixty-seven (97.1%) had a smartphone and/or tablet PC. Smartphone and/or tablet PC were used since 3.7 (SD = 2.17; min-max = 0-12) years. Sixty-one (35.5%) felt that smartphone and/or tablet PC are very important, 92 (53.5%) important, 2 (1.2%) unimportant and 12 (7%) were undecided about this. One hundred eleven (64.5%) participants had a medical application on the smartphone and 66 (38.4%) on the tablet PC. They used 1.7 (SD = 2.04; min-max = 0-10) medical applications for 1.45 (SD = 2.53; min-max = 0-25) times on average. Eighty respondents (66.7%) used a medical application for any medical problem. CONCLUSIONS: Almost all family physicians used smartphone and/or tablet PC during daily practice, and the reason of use was commonly for communication and Internet purposes. Usage during working hours was limited, but medical apps were perceived mainly positively for receiving medical information via Internet. Looking at the medical apps' acceptability scale, participants were in agreement with the security, cost, contents' quality, ease of use, support, ease of finding, ease of accessing and motivation to use medical applications. PMID- 26552717 TI - Near-infrared (NIR) up-conversion optogenetics. AB - Non-invasive remote control technologies designed to manipulate neural functions have been long-awaited for the comprehensive and quantitative understanding of neuronal network in the brain as well as for the therapy of neurological disorders. Recently, it has become possible for the neuronal activity to be optically manipulated using biological photo-reactive molecules such as channelrhodopsin (ChR)-2. However, ChR2 and its relatives are mostly reactive to visible light, which does not effectively penetrate through biological tissues. In contrast, near-infrared (NIR) light (650-1450 nm) penetrates deep into the tissues because biological systems are almost transparent to light within this so called 'imaging window'. Here we used lanthanide nanoparticles (LNPs), composed of rare-earth elements, as luminous bodies to activate ChRs since they absorb low energy NIR light to emit high-energy visible light (up-conversion). Here, we created a new type of optogenetic system which consists of the donor LNPs and the acceptor ChRs. The NIR laser irradiation emitted visible light from LNPs, then induced the photo-reactive responses in the near-by cells that expressed ChRs. However, there remains room for large improvements in the energy efficiency of the LNP-ChR system. PMID- 26552718 TI - Vinorelbine therapy in classic Kaposi's sarcoma: a retrospective study of 20 patients. AB - BACKGROUND: Systemic chemotherapy is the main treatment of diffuse and/or aggressive classic Kaposi's sarcoma (KS) but there are no standard treatment guidelines and published literature regarding vinorelbine is lacking. OBJECTIVES: To assess the safety and effectiveness of intravenous vinorelbine in the treatment of classic KS. MATERIALS & METHODS: We performed a retrospective study of a departmental database in histologically proven classic KS. RESULTS: Twenty patients received intravenous vinorelbine as cycles of 20 mg/m(2) once every two weeks for 5 cycles and subsequently at a dose of 30 mg/m(2) once every three weeks. Of 19 assessable patients, three (16%) had a complete remission and 11 (58%) had a partial response, for an overall response rate of 74%. The remaining 5 patients had a stable disease (26%). Grade 3 or 4 toxicities were neutropenia (3/20 patients), deep vein thrombosis (1/20 patients) and constipation (1/20 patients). The median progression-free survival from the start of therapy until the development of progressive disease was 35.1 months. CONCLUSION: Vinorelbine is an effective and overall well tolerated treatment for classic KS. PMID- 26552719 TI - Adaptation of H9N2 AIV in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets. AB - H9N2 avian influenza viruses circulate worldwide in poultry and have sporadically infected humans, raising concern whether H9N2 viruses have pandemic potential. Here, we use a guinea pig model to examine whether serial passage results in adaptive viral changes that confer a transmissible phenotype to a wild-type H9N2 virus. After nine serial passages of an H9N2 virus through guinea pigs, productive transmission by direct contact occurred in 2/3 guinea pig pairs. The efficiency of transmission by direct contact increased following the fifteenth passage and occurred in 3/3 guinea pig pairs. In contrast, airborne transmission of the passaged virus was less efficient and occurred in 1/6 guinea pig pairs and 0/6 ferret pairs after the fifteenth passage. Three amino acid substitutions, HA1 Q227P, HA2-D46E, and NP-E434K, were sufficient for contact transmission in guinea pigs (2/3 pairs). The two HA amino acid substitutions enhanced receptor binding to alpha2,3-linked sialic acid receptors. Additionally, the HA2-D46E substitution increased virus thermostability whereas the NP-E434K mutation enhanced viral RNA polymerase activity in vitro. Our findings suggest that adaptive changes that enhance viral receptor binding, thermostability, and replicative capacity in mammalian cells can collectively enhance the transmissibility of H9N2 AIVs by direct contact in the guinea pig model. PMID- 26552720 TI - Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices. AB - The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings. PMID- 26552721 TI - Oriented Liquid Crystalline Polymer Semiconductor Films with Large Ordered Domains. AB - Large strains are applied to liquid crystalline poly(2,5-bis(3-tetradecylthiophen 2yl)thieno(3,2-b)thiophene) (pBTTT) films when held at elevated temperatures resulting in in-plane polymer alignment. We find that the polymer backbone aligns significantly in the direction of strain, and that the films maintain large quasi domains similar to that found in spun-cast films on hydrophobic surfaces, highlighted by dark-field transmission electron microscopy imaging. The highly strained films also have nanoscale holes consistent with dewetting. Charge transport in the films is then characterized in a transistor configuration, where the field effect mobility is shown to increase in the direction of polymer backbone alignment, and decrease in the transverse direction. The highest saturated field-effect mobility was found to be 1.67 cm(2) V(-1) s(-1), representing one of the highest reported mobilities for this material system. The morphology of the oriented films demonstrated here contrast significantly with previous demonstrations of oriented pBTTT films that form a ribbon-like morphology, opening up opportunities to explore how differences in molecular packing features of oriented films impact charge transport. Results highlight the role of grain boundaries, differences in charge transport along the polymer backbone and pi-stacking direction, and structural features that impact the field dependence of charge transport. PMID- 26552722 TI - Utilization of Donors with Hepatitis B Core Antibodies in Liver Transplantation. AB - BACKGROUND: At present, the scarcity of organs is one of the major problems in transplantation. We present our own experience in expanding the acceptance criteria for deceased donors. We aimed to evaluate the potential impact of using hepatitis B virus (HBV) core antibody (anti-HBc)-positive donor grafts on the long-term liver transplantation results. MATERIAL AND METHODS: We retrospectively analyzed data from 324 consecutive liver transplantation procedures performed in the largest transplant center in Poland, between January 2007 and February 2012. These patients included 36 who had received a liver from anti-HBc-positive donors. RESULTS: The presence of anti-HBc antibodies in the donor did not have a significant negative impact on the overall 3-year patient or graft survival rates. Among recipients with pre-transplant HBV infection, patients who received an organ from an anti-HBc-positive donor tended to have an improved survival rate compared with patients who received liver transplants from seronegative donors (p=0.080). However, there was a statistically significant reduction in graft survival (p=0.035) in the recipients without serological markers of HBV infection who received liver transplants harvested from anti-HBc-positive donors. CONCLUSIONS: These results confirm the validity of extending the acceptance criteria to anti-HBc-positive donors, particularly for patients with a prior HBV infection. Despite the increased risk of graft loss, liver transplantation from anti-HBc-positive donors among recipients not infected with HBV may also be considered in appropriate cases. PMID- 26552723 TI - Proteomics of cell-cell interactions in health and disease. AB - The mechanisms of cell-cell communications are now under intense study by proteomic approaches. Proteomics has unraveled changes in protein profiling as the result of cell interactions mediated by ligand/receptor, hormones, soluble factors, and the content of extracellular vesicles. Besides being a brief overview of the main and profitable methodologies now available (evaluating theory behind the methods, their usefulness, and pitfalls), this review focuses on-from a proteome perspective-some signaling pathways and post-translational modifications (PTMs), which are essential for understanding ischemic lesions and their recovery in two vital organs in mammals, the heart, and the kidney. Knowledge of misdirection of the proteome during tissue recovery, such as represented by the convergence between fibrosis and cancer, emerges as an important tool in prognosis. Proteomics of cell-cell interaction is also especially useful for understanding how stem cells interact in injured tissues, anticipating clues for rational therapeutic interventions. In the effervescent field of induced pluripotency and cell reprogramming, proteomic studies have shown what proteins from specialized cells contribute to the recovery of infarcted tissues. Overall, we conclude that proteomics is at the forefront in helping us to understand the mechanisms that underpin prevalent pathological processes. PMID- 26552724 TI - Patients' and carers' experiences of UK memory services. AB - OBJECTIVE: The objective of this study is to test the validity of an accreditation programme for memory services in the UK by investigating whether different levels of accreditation status (excellent compared with accredited) are reflected in patients' and carers' reported satisfaction. METHOD: A comparison of survey data from patient and carer feedback questionnaires collected from services as part of the accreditation process. RESULTS: Five hundred and eighty three patient questionnaires and 663 carer questionnaires were returned from 41 services. Patients and carers who attended memory services which were later 'accredited as excellent', were more likely than those who had visited 'accredited' services to have: been given written information about a variety of topics; been asked for feedback about using the memory service; and had found it easier to get to their appointments. Carers attending services accredited as excellent were more likely to have been offered an assessment of their needs. CONCLUSION: Patients and carers had very good experiences of memory services overall whether they had standard or excellent accreditation. However, 'excellent' services were consistently better on a number of factors. This provides further support that the accreditation process is an important indicator of the quality of memory services. PMID- 26552725 TI - COD, nutrient removal and disinfection efficiency of a combined subsurface and surface flow constructed wetland: A case study. AB - A constructed wetland system composed of a subsurface flow wetland, a surface flow wetland and a facultative pond was studied from July 2008 until May 2012. It was created to treat the domestic sewage produced by a hamlet of 150 inhabitants. Monthly physicochemical and microbiological analyses were carried out in order to evaluate the removal efficiency of each stage of the process and of the total treatment system. Pair-wise Student's t-tests showed that the mean removal of each considered parameter was significantly different (alpha = 0.05) between the various treatment phases. Two-way ANOVA and Tukey's HSD tests were used to find significant differences between wetland types and seasons in the removal efficiency of the considered water quality parameters. Significant differences in percent removal efficiency between the treatment phases were observed for total phosphorus, total nitrogen, ammonia nitrogen and organic load (expressed as Chemical Oxygen Demand). In general, the wastewater treatment was carried by the sub-superficial flow phase mainly, both in growing season and in quiescence season. Escherichia coli removal ranged from 98% in quiescence season to >99% in growing season (approximately 2-3 orders of magnitude). The inactivation of fecal bacteria was not influenced by the season, but only by the treatment phase. PMID- 26552726 TI - Wing patterning genes and coevolution of Mullerian mimicry in Heliconius butterflies: Support from phylogeography, cophylogeny, and divergence times. AB - Examples of long-term coevolution are rare among free-living organisms. Mullerian mimicry in Heliconius butterflies had been suggested as a key example of coevolution by early genetic studies. However, research over the last two decades has been dominated by the idea that the best-studied comimics, H. erato and H. melpomene, did not coevolve at all. Recently sequenced genes associated with wing color pattern phenotype offer a new opportunity to resolve this controversy. Here, we test the hypothesis of coevolution between H. erato and H. melpomene using Bayesian multilocus analysis of five color pattern genes and five neutral genetic markers. We first explore the extent of phylogenetic agreement versus conflict between the different genes. Coevolution is then tested against three aspects of the mimicry diversifications: phylogenetic branching patterns, divergence times, and, for the first time, phylogeographic histories. We show that all three lines of evidence are compatible with strict coevolution of the diverse mimicry wing patterns, contrary to some recent suggestions. Instead, these findings tally with a coevolutionary diversification driven primarily by the ecological force of Mullerian mimicry. PMID- 26552727 TI - Gapless quantum spin liquid ground state in the two-dimensional spin-1/2 triangular antiferromagnet YbMgGaO4. AB - Quantum spin liquid (QSL) is a novel state of matter which refuses the conventional spin freezing even at 0 K. Experimentally searching for the structurally perfect candidates is a big challenge in condensed matter physics. Here we report the successful synthesis of a new spin-1/2 triangular antiferromagnet YbMgGaO4 with symmetry. The compound with an ideal two dimensional and spatial isotropic magnetic triangular-lattice has no site-mixing magnetic defects and no antisymmetric Dzyaloshinsky-Moriya (DM) interactions. No spin freezing down to 60 mK (despite thetaw ~ -4 K), the power-law temperature dependence of heat capacity and nonzero susceptibility at low temperatures suggest that YbMgGaO4 is a promising gapless (<=|thetaw|/100) QSL candidate. The residual spin entropy, which is accurately determined with a non-magnetic reference LuMgGaO4, approaches zero (<0.6%). This indicates that the possible QSL ground state (GS) of the frustrated spin system has been experimentally achieved at the lowest measurement temperatures. PMID- 26552728 TI - Artificial Photosynthesis at Dynamic Self-Assembled Interfaces in Water. AB - Artificial photosynthesis is one of the big scientific challenges of today. Self assembled dynamic interfaces, such as vesicles or micelles, have been used as microreactors to mimic biological photosynthesis. These aggregates can help to overcome typical problems of homogeneous photocatalytic water splitting. Microheterogeneous environments organize catalyst-photosensitizer assemblies at the interface in close proximity and thus enhance intermolecular interactions. Thereby vesicles and micelles may promote photoinitiated charge separation and suppress back electron transfer. The dynamic self-assembled interfaces solubilize non-polar compounds and protect sensitive catalytic units and intermediates against degradation. In addition, vesicles provide compartmentation that was used to separate different redox environments needed for an overall water splitting system. This Minireview provides an overview of the applications of micellar and vesicular microheterogeneous systems for solar energy conversion by photosensitized water oxidation and hydrogen generation. PMID- 26552729 TI - Optimal detection of infratentorial lesions with a combined dual-echo MRI sequence: "PT2". AB - BACKGROUND: The infratentorial compartment is cardinal for multiple sclerosis (MS) diagnosis. T2-weighted (T2) and proton density-weighted (PD) magnetic resonance imaging (MRI) can visualize infratentorial lesions, but only suboptimally. OBJECTIVE: To combine PD and T2 for better lesion assessment. METHODS: T2 and PD from 35 cases were averaged to form "PT2" images. Two raters counted infratentorial lesions and qualitatively assessed their conspicuity. RESULTS: PT2 showed 244 infratentorial lesions, of which 94% and 74% were seen in PD and T2. PT2 received higher grades for image quality and lesion conspicuity (p < 0.001 for all comparisons). CONCLUSION: PT2 could improve our ability to diagnose and monitor MS. PMID- 26552731 TI - Are we in need of NEDA? PMID- 26552730 TI - Seronegative neuromyelitis optica spectrum disorder patients diagnosed using new diagnostic criteria. AB - BACKGROUND: Recently, new diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) were published. OBJECTIVE: Our primary aim was to evaluate the usefulness of the new diagnostic criteria in anti-aquaporin 4 (AQP4) antibody negative cases. METHODS: Consecutive 471 patients whose anti-AQP4 antibody was measured at Chiba University were reviewed. RESULTS: Four anti-AQP4 antibody negative-patients, who fulfilled the new diagnostic criteria for NMOSD but not 2006 diagnostic criteria for neuromyelitis optica (NMO), were identified. They showed high cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels, an absence of oligoclonal bands and/or cloud-like enhancement on magnetic resonance imaging, which are compatible findings for NMO. CONCLUSION: The new diagnostic criteria are clinically useful in seronegative NMOSD. PMID- 26552732 TI - Impaired growth of the cerebellum in pediatric-onset acquired CNS demyelinating disease. AB - BACKGROUND: Acquired demyelinating syndromes (ADS) have the potential to negatively impact cerebellar growth, given the proclivity for infratentorial lesions in pediatric-onset multiple sclerosis (MS) and ADS. OBJECTIVE: To investigate cerebellar growth longitudinally in pediatric ADS. METHODS: Cerebellar volumes from 472 magnetic resonance imaging (MRI) scans of 98 patients with monophasic ADS (monoADS), monophasic acute disseminated encephalomyelitis (ADEM), and MS (49 girls; mean age: 11.4 years at first scan, mean follow-up: 3.1 years) imaged serially from onset and 897 MRI scans of 418 healthy children (223 girls, mean age: 11.3 years, mean follow-up: 2.9 years) were segmented automatically, analyzed with mixed-effect models, and compared with cerebral volume. RESULTS: Cerebellar developmental trajectories followed a U-shaped curve, showing larger volumes in boys (p < 0.001). Cerebellar volumes in all three patient groups failed to reach age-expected trajectories, leading to significantly smaller volumes, notably in the posterior lobes. Cerebellar volume reductions were of a similar magnitude to cerebral volume reductions. Cerebellar white matter volume declined in MS and ADEM patients over time, while in monoADS patients it remained similar to controls. Cerebellar volumes did not correlate either with lesion volumes at onset or with physical disability. CONCLUSION: MonoADS, ADEM, and MS in childhood lead to impaired age-expected growth of the cerebellum. PMID- 26552733 TI - Modified Frailty Index (mFI) in major gynaecological surgery: does it predict outcome? PMID- 26552734 TI - Germline copy number variation analysis in Finnish families with hereditary prostate cancer. AB - BACKGROUND: The inherited factors that predispose individuals to prostate cancer (PrCa) remain largely unknown. The aim of this study was to identify germline copy number variants (CNVs) in Finnish individuals that could contribute to an increased PrCa risk. METHODS: Genome-wide CNV screening was performed by analyzing single nucleotide polymorphisms from 105 PrCa patients and 37 unaffected relatives, representing 31 Finnish hereditary PrCa (HPC) families. The CNVs that aggregated in affected individuals and overlapped with genes implicated in cancer were validated using quantitative PCR in 189 index patients from Finnish HPC families and in 476 controls. RESULTS: An intronic deletion (14.7 kb) in the EPHA3 gene coding for class A ephrin receptor was observed in 11.6% of PrCa patients and in 6.1% of controls. The deletion associated with an increased PrCa risk (P = 0.018, OR = 2.06, 95%CI = 1.18-3.61). Although incomplete segregation with affection status was observed, the results show that the deletion was overrepresented in PrCa patients (56.1%) when compared to unaffected male relatives (31.2%). Interestingly, PrCa-specific mortality was higher among EPHA3 deletion carriers (24.3%) than among patients with a normal EPHA3 copy number (3.4%). CONCLUSIONS: This study is the first investigation of the contribution of germline CNVs to HPC susceptibility in Finland. A novel association between the EPHA3 deletion and PrCa risk was observed and, if confirmed, screening for this variant may aid in risk stratification among HPC patients. PMID- 26552735 TI - Impact of Continuous Positive Airway Pressure Therapy on Atrial Electromechanical Delay in Obesity-Hypoventilation Syndrome Patients. AB - BACKGROUND: Obesity-hypoventilation syndrome (OHS) is defined as daytime hypercapnia and hypoxemia in obese patients with sleep-disordered breathing. We evaluated the electrocardiographic P-wave duration and dispersion (PD) and echocardiographic noninvasive indicators of atrial conduction heterogeneity in OHS patients and the impact of CPAP on atrial conduction and atrial fibrillation incidence. METHODS AND RESULTS: We enrolled 50 OHS patients and 50 sex- and age matched obese subjects as control. Study population underwent cardiologic evaluation and polysomnography before enrollment, at 1- and 6-month follow-ups after CPAP therapy. The OHS group showed a significant increase in inter-atrial (35.2 +/- 8 milliseconds vs. 20.1 +/- 2.7 milliseconds, P < 0.0001), intra-left (30.5 +/- 7.2 milliseconds vs. 16.5 +/- 2 milliseconds, P < 0.0001), and intra right atrial electromechanical delays (AEMD)(24.8 +/- 10 milliseconds vs. 15 +/- 2.6 milliseconds, P < 0.0001) as well as in Pmax (130 +/- 7.4 milliseconds vs. 97 +/- 7.2 milliseconds, P = 0.002) and PD (56.5 +/- 8.5 milliseconds vs. 31 +/- 7.2 milliseconds, P = 0.002) compared to the control group. Significant improvement was noted after 6 months of CPAP therapy in inter-atrial (35.2 +/- 8 milliseconds vs. 24.5 +/- 6.3 milliseconds, P < 0.0001), intra-left (30.5 +/- 7.2 milliseconds vs. 20.6 +/- 5 milliseconds, P = 0.003), and intra-right AEMD (24.8 +/- 10 milliseconds vs. 17 +/- 7.5 milliseconds, P < 0.0001), as well as in Pmax (130 +/ 7.4 milliseconds vs. 95 +/- 10 milliseconds, P < 0.0001) and in PD (56.5 +/- 8.5 milliseconds vs. 32.5 +/- 6 milliseconds, P < 0.0001) in the OHS group. External loop recorder monitoring detected paroxysmal AF in 19 OHS patients (38%) with significant reduction in paroxysmal AF episodes (12 +/- 6 vs. 47 +/- 12, P < 0.0001) after 6-month CPAP therapy. CONCLUSION: Our findings showed a significant increase of electrocardiographic and echocardiographic indexes of atrial conduction heterogeneity in OHS patients. The CPAP therapy, having a positive impact on atrial conduction time, seems to reduce AF incidence in OHS patients. PMID- 26552736 TI - Disc degeneration implies low back pain. AB - BACKGROUND: Low back pain exerts a tremendous burden on individual patients and society due to its prevalence and ability to cause long-term disability. Contemporary treatment and prevention efforts are stymied by the absence of a confirmed cause for the majority of low back pain patients. METHODS: A system dynamics approach is used to build a physiologically-based model investigating the relationship between disc degeneration and low back pain. The model's predictions are evaluated under two different types of study designs and compared with established observations on low back pain. RESULTS: A three-compartment model (no disc degeneration, disc degeneration with pain remission, disc degeneration with pain recurrence) accurately predicts the age-specific prevalence observed in one of the largest population-based surveys (R (2) = 0.998). The estimated transition age at which intervertebral discs lose the growth potential and begin degenerating is 13.3 years. The estimated disc degeneration rate is 0.0344/year. Without any additional change being made to parameter's values, the model also fully accounts for the age-specific prevalence of disc degeneration detected with a lumbar MRI among asymptomatic individuals (R (2) = 0.978). CONCLUSIONS: Dual testing of the proposed mechanistic model with two independent data sources (one with lumbar MRI and the other without) confirm that disc degeneration is the driving force behind and cause of age dependence in low back pain. Observed complexity of low back pain epidemiology arises from the slow dynamics of disc degeneration coupled with the fast dynamics of disease recurrence. PMID- 26552737 TI - From raw data to data-analysis for magnetic resonance spectroscopy--the missing link: jMRUI2XML. AB - BACKGROUND: Magnetic resonance spectroscopy provides metabolic information about living tissues in a non-invasive way. However, there are only few multi-centre clinical studies, mostly performed on a single scanner model or data format, as there is no flexible way of documenting and exchanging processed magnetic resonance spectroscopy data in digital format. This is because the DICOM standard for spectroscopy deals with unprocessed data. This paper proposes a plugin tool developed for jMRUI, namely jMRUI2XML, to tackle the latter limitation. jMRUI is a software tool for magnetic resonance spectroscopy data processing that is widely used in the magnetic resonance spectroscopy community and has evolved into a plugin platform allowing for implementation of novel features. RESULTS: jMRUI2XML is a Java solution that facilitates common preprocessing of magnetic resonance spectroscopy data across multiple scanners. Its main characteristics are: 1) it automates magnetic resonance spectroscopy preprocessing, and 2) it can be a platform for outputting exchangeable magnetic resonance spectroscopy data. The plugin works with any kind of data that can be opened by jMRUI and outputs in extensible markup language format. Data processing templates can be generated and saved for later use. The output format opens the way for easy data sharing- due to the documentation of the preprocessing parameters and the intrinsic anonymization--for example for performing pattern recognition analysis on multicentre/multi-manufacturer magnetic resonance spectroscopy data. CONCLUSIONS: jMRUI2XML provides a self-contained and self-descriptive format accounting for the most relevant information needed for exchanging magnetic resonance spectroscopy data in digital form, as well as for automating its processing. This allows for tracking the procedures the data has undergone, which makes the proposed tool especially useful when performing pattern recognition analysis. Moreover, this work constitutes a first proposal for a minimum amount of information that should accompany any magnetic resonance processed spectrum, towards the goal of achieving better transferability of magnetic resonance spectroscopy studies. PMID- 26552738 TI - Self-Rated Health Across Race, Ethnicity, and Immigration Status for US Adolescents and Young Adults. AB - PURPOSE: Health disparities research seeks to understand and eliminate differences in health based on social status. Self-rated health is often used to document health disparities across racial/ethnic and immigrant groups, yet its validity for such comparative research has not been established. To be useful in disparities research, self-rated health must measure the same construct in all groups, that is, a given level of self-rated health should reflect the same level of mental and physical health in each group. This study asks, Is the relationship between self-rated health and four indicators of health status--body mass index, chronic conditions, functional limitations, and depressive symptoms--similar for adolescents and young adults of different races/ethnicities and immigrant generations? METHODS: Ordinary least squares regression was used to examine associations of self-rated health with the four indicators of health status both cross-sectionally and longitudinally using four waves of the National Longitudinal Study of Adolescent to Adult Health. RESULTS: Health indicators explained similar amounts of variance in self-rated health for all racial/ethnic and immigrant generation groups. The cross-sectional association between the health indicators and self-rated health did not vary across groups. The longitudinal association between depressive symptoms and chronic conditions and self-rated health also did not differ across groups. However, an increase in body mass index was associated more negatively with later self-rated health for Asians than for whites or blacks. CONCLUSIONS: Self-rated health is valid for disparities research in large, population-based surveys of US adolescents and young adults. In many of these surveys self-rated health is the only measure of health. PMID- 26552739 TI - Characteristics of a Favorable Weight Status Change From Adolescence to Young Adulthood. AB - PURPOSE: To explore 10-year longitudinal predictors (personal, psychological, behavioral, and socioenvironmental) of exiting obesity from adolescence to young adulthood. METHODS: Data were collected from a population-based cohort of adolescents (n = 2,287) attending middle/high schools in Minneapolis-St. Paul in 1998-1999 (mean age = 14.9) and again in 2008-2009 (mean age = 25.3) participating in Project Eating and Activity Among Teens and Young Adults. Self reported height and weight were used to calculate weight status change between adolescence and young adulthood, among participants with obesity at baseline (n = 175). Questionnaires assessed personal, psychological, behavioral, and socioenvironmental factors hypothesized to play a role in obesity. Modified Poisson regressions estimated adjusted relative risks (RRs) for exiting obesity as a function of each baseline and 10-year change in predictor, controlling for relevant covariates. RESULTS: Thirty-two percent of adolescents exited obesity in young adulthood. Reductions in fast food intake (RR = .73, 95% confidence interval [CI] = .61-.87) and screen time (RR = .98, 95% CI = .96-.99), and increases in fruit/vegetable intake (RR = 1.06, 95% CI 1.01-1.12), moderate-to vigorous physical activity (RR = 1.06, 95% CI = 1.00-1.12), home fruit/vegetable availability (RR = 1.58, 95% CI = 1.19-2.09), family meals (RR = 1.12, 95% CI = 1.03-1.22), and serving vegetables at dinner (RR = 1.45, 95% CI = 1.10-1.92) were associated with exiting obesity. Not dieting as an adolescent and improvements in body satisfaction, depressive symptoms, self-esteem, and weight teasing were also associated with exiting obesity. CONCLUSIONS: Promoting healthy eating and activity, and improving the healthfulness of home food environments may be promising intervention targets for promoting healthier weights in adolescents and young adults with obesity. Addressing dieting behavior and the psychosocial health of adolescents with obesity may also be needed throughout the transition to young adulthood. PMID- 26552740 TI - Lunchtime School Water Availability and Water Consumption Among California Adolescents. AB - PURPOSE: To examine the potential impact of California SB 1413, which required school districts to provide free, fresh drinking water during mealtimes in food service areas by July 1, 2011, on greater water consumption among California adolescents. METHODS: Data were drawn from the 2012 and 2013 state-representative California Health Interview Survey. A total of 2,665 adolescents aged 12-17 years were interviewed regarding their water consumption and availability of free water during lunchtime at their school. RESULTS: Three-fourths reported that their school provided free water at lunchtime, mainly via fountains. In a multivariate model that controlled for age, gender, income, race/ethnicity, body mass index, and school type, adolescents in schools that provided free water consumed significantly more water than adolescents who reported that water was not available, bivariate (standard error) = .67 (.28), p = .02. School water access did not significantly vary across the 2 years. CONCLUSIONS: Lunchtime school water availability was related to water consumption, but a quarter of adolescents reported that their school did not provide free water at lunch. Future research should explore what supports and inducements might facilitate provision of drinking water during school mealtimes. PMID- 26552741 TI - Polyunsaturated fat intake and mortality in non-statin users, is there an independent relationship? The authors reply. PMID- 26552742 TI - The effect of a dietary portfolio compared to a DASH-type diet on blood pressure. AB - BACKGROUND AND AIM: Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na(+)), potassium (K(+)), and portfolio components. METHODS AND RESULTS: 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to -0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (rho = -0.15 to -0.17, p <= 0.016) as did urinary potassium (rho = -0.25, p = 0.001), while the Na(+)/K(+) ratio was positively associated (rho = 0.20, p = 0.010). CONCLUSIONS: Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH type diet. CLINICAL TRIAL REG. NO.: NCT00438425, clinicaltrials.gov. PMID- 26552744 TI - Coupled resonances allow studying the aging of adhesive contacts between a QCM surface and single, micrometer-sized particles. AB - Interparticle contacts and contacts between particles and surfaces are known to change over time. The contact area, the contact stiffness, and the contact strength usually increase as the contact ages. Contact aging is mostly driven by capillary forces, but also by plastic deformation. Making use of acoustic resonators, we have studied the stiffness of contacts between the surface of a quartz crystal microbalance (QCM) and individual, micrometer-sized particles adsorbed to the resonator surface. Studying single particles avoids ensemble averaging. Central to the analysis is the coupled resonance, occurring when a surface-attached particle together with the link forms a resonator of its own. If the frequency of this second resonator comes close to one of the crystal's overtones, plots of shifts in resonance bandwidth versus overtone order display a resonance curve. This secondary resonance is caused by the coupling between the particle's resonance and the main resonance. One can read the frequency of the coupled resonance from this plot. Similarly, resonance curves are observed in plots of frequency and bandwidth versus time, if the contact stiffness varies smoothly with time. Because the coupled resonance is a characteristic feature, it is easily identified even in cases where frequency shifts of some other origin are superimposed onto the data. For the cases studied here, the links stiffened while they dried. Interestingly, the efficiency of coupling between the particle resonance and the main resonance decreased at the same time. This can be explained with an increase in the link's bending stiffness. The analysis highlights that a QCM experiment amounts to vibrational spectroscopy on surface attached particles. Among the application examples is the adsorption and drying of a lycopodium spore. Clearly, the technique is also applicable to problems of bioadhesion. PMID- 26552743 TI - Lower-normal TSH is associated with better metabolic risk factors: A cross sectional study on Spanish men. AB - BACKGROUND AND AIMS: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. METHODS AND RESULTS: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. CONCLUSIONS: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles. PMID- 26552745 TI - Esculin improves dyslipidemia, inflammation and renal damage in streptozotocin induced diabetic rats. AB - BACKGROUND: Increasing studies have shown that dyslipidemia and inflammatory responses play important roles in the progression of microvascular diabetic complications. Esculin (ES), a coumarin derivative, was extracted from Fraxinus rhynchophylla. The present study was to evaluate the potential effects of ES on lipid metabolism, inflammation responses and renal damage in streptozotocin (STZ) induced experimental diabetic rats and explore the possible mechanism. METHODS: Diabetic rat model was established by administration high-glucose-fat diet and intraperitoneal injection of STZ 45 mg/kg. ES was administrated to diabetic rats intragastrically at 10, 30 and 90 mg/kg for 10 weeks respectively. The levels of triglycerides (TG), total cholesterol (T-CHO), low density lipoproteins (LDL), and high-density-cholesterol (HDL-C) in serum were measured. IL-1, IL-6, ICAM-1, NO, NAGL, and AGEs level in serum were detected by ELISA assay. The accumulation of AGEs in kidney tissue was examined by immunohistochemistry assay. RESULTS: The results showed that ES could decrease TG, T-CHO, LDL levels in serum of diabetic rats in a dose dependent manner. ES also decreased IL-1, IL-6, ICAM-1, NO and NGAL levels in serum of diabetic rats in a dose dependent manner. Furthermore, ES at 30 and 90 mg/kg significantly decreased AGEs level in serum and alleviated AGEs accumulation in renal in diabetic rats. CONCLUSIONS: Our findings indicate that ES could improve dyslipidemia, inflammation responses, renal damage in STZ induced diabetic rats and the possible mechanism might be associated with the inhibition of AGEs formation. PMID- 26552746 TI - Microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer. AB - BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy, with limited treatment options for chemoresistant disease. An important link between inflammation and peritoneal spread of ovarian cancer is NF-kappaB signaling. Thymoquinone (TQ) exerts multiple anti-tumorigenic cellular effects, including NF kappaB inhibition. We aimed to investigate the therapeutic potential of TQ in an established murine syngeneic model of ovarian cancer. METHODS: ID8-NGL mouse ovarian cancer cells stably expressing an NF-kappaB reporter transgene were injected intra-peritoneally into C57BL/6 mice, and mice were treated with TQ or vehicle for 10 or 30 days. TQ was combined with the macrophage depleting drug, liposomal clodronate, in selected experiments. Effects on peritoneal tumor burden were measured by volume of ascites, number of peritoneal implants and mesenteric tumor mass. NF-kappaB reporter activity and markers of proliferation and apoptosis were measured in tumors and in confirmatory in vitro experiments. Protein or mRNA expression of M1 (anti-tumor) and M2 (pro-tumor) macrophage markers, and soluble cytokine profiles, were examined from harvested ascites fluid, peritoneal lavages and/or tumor sections. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments. RESULTS: Consistent with its effects in vitro, TQ reduced proliferation and increased apoptosis in ID8-NGL tumors after 10 and 30 day treatment. Prolonged TQ treatment did not significantly alter tumor number or mass compared to vehicle, but rather exerted an overall deleterious effect by stimulating ascites formation. Increased ascites was accompanied by elevated NF-kappaB activity in tumors and macrophages, increased pro-tumor M2 macrophages and expression of pro-tumorigenic soluble factors such as VEGF in ascites fluid, and increased tumor infiltration of M2 macrophages. In contrast, a 10 day exposure to TQ produced no ascites, and reduced tumor NF-kappaB activity, M2 macrophages and soluble VEGF levels. Peritoneal macrophage depletion by clodronate significantly reduced tumor burden. However, TQ-stimulated ascites was further enhanced by co-treatment with clodronate, with macrophages present overwhelmingly of the M2 phenotype. CONCLUSIONS: Our findings show that pro-tumorigenic microenvironmental effects limited the efficacy of TQ in a syngeneic mouse model of ovarian cancer, and provide caution regarding its potential use in clinical trials in ovarian cancer patients. PMID- 26552747 TI - Comprehensive therapeutic approach for patients with heart failure and comorbidity. AB - The prevalence of heart failure increases with age and is accompanied by other diseases, which are encompassed within a "cardiometabolic phenotype". Their interrelation changes the evolution and treatment that each disease would have in isolation. Patients with heart failure and comorbidity are frail and complex. They require a comprehensive assessment (not just biomedical), which includes functional, cognitive, affective and psychosocial aspects. The overall treatment, which is not covered in the clinical practice guidelines, should adapt to each and every one of the comorbidities. Polypharmacy should be avoided as much as possible, due to its interactions and reduced adherence. Treatment needs to be optimised and adapted to the evolutionary phase of the disease and the specific needs of each patient. The complexity of the care process for patients with heart failure and comorbidities requires the coordination of healthcare providers and support from family and others involved in the patient's care. PMID- 26552748 TI - Opinion Paper: Selective Targeting of Liver Nodules. Present Situation and New Challenges to Enhance Indocyanine Green Captation from Colorectal Liver Metastases. PMID- 26552749 TI - Investigations in sono-enzymatic degradation of ibuprofen. AB - The drug ibuprofen (IBP) appears frequently in the wastewater discharge from pharmaceutical industries. This paper reports studies in degradation of IBP employing hybrid technique of sono-enzymatic treatment. This paper also establishes synergy between individual mechanisms of enzyme and sonolysis for IBP degradation by identification of degradation intermediates, and Arrhenius & thermodynamic analysis of the experimental data. Positive synergy between sonolysis and enzyme treatment is attributed to formation of hydrophilic intermediates during degradation. These intermediates form due to hydroxylation and oxidation reactions induced by radicals formed during transient cavitation. Activation energy and enthalpy change in sono-enzymatic treatment are lower as compared to enzyme treatment, while frequency factor and entropy change are higher as compared to sonolysis. Degradation of IBP in sono-enzymatic treatment is revealed to be comparable with other hybrid techniques like photo-Fenton, sono photocatalysis, and sono-Fenton. PMID- 26552751 TI - Stand-Your-Ground is losing ground for racial minorities' health. PMID- 26552750 TI - Chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26. AB - BACKGROUND: Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12. METHODS: We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays. RESULTS: 5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations. CONCLUSION: Our results indicate that conventional anticancer agents may act to inhibit chemokine-mediated migration through eradication of CXCR4+ cells and attenuation of chemokine gradients through elevation of CD26 activity. PMID- 26552753 TI - Phrenic nerve palsy in cryoballoon ablation: Can it be prevented? PMID- 26552752 TI - Negative concordance pattern in bipolar and unipolar recordings: An additional mapping criterion to localize the site of origin of focal ventricular arrhythmias. AB - BACKGROUND: The relevance of the temporal relationship between a unipolar electrogram (UEGM) and a bipolar electrogram (BEGM) in determining the site of origin (SOO) of focal arrhythmias has been largely demonstrated. OBJECTIVE: We sought to demonstrate that a negative concordance in the initial forces of these EGMs is also helpful in predicting the SOO of premature ventricular contractions (PVCs). METHODS: Mapping and radiofrequency (RF) ablation were performed in 41 patients with symptomatic PVCs in the absence of structural heart disease. Simultaneous recordings of the minimally filtered (0.5-500 Hz) UEGM and filtered BEGM (30-500 Hz) were analyzed at 247 mapping sites, where RF was attempted. EGMs of 63 mechanically induced PVCs were separately analyzed as a validation group. All ablation sites had a QS pattern in the UEGM. Acute PVC suppression was defined as a complete disappearance of ventricular ectopic beats after a 60 second pulse of RF. RESULTS: RF ablation obtained PVC suppression (RF+) in 33 of 247 sites (13.3%). A negative concordance pattern (NCP) during the initial 20 ms of both UEGM and BEGM was observed in 31 of 33 (94%) RF+ sites compared with 10 of 214 (4%)RF- sites (P < .0001). The NCP criterion demonstrated to be an additional powerful predictor of acute RF success with sensitivity, specificity, positive predictive value, and negative predictive value of 94%, 95%, 76%, and 99%, respectively. Similarly to RF+ sites, the NCP was observed in 60 of 63 sites (95.2%) in the mechanical PVC group. CONCLUSION: An NCP in both UEGM and BEGM may be an additional criterion that helps to localize the SOO of focal ventricular arrhythmias. PMID- 26552754 TI - Optimal QT interval correction formula in sinus tachycardia for identifying cardiovascular and mortality risk: Findings from the Penn Atrial Fibrillation Free study. AB - BACKGROUND: The QT interval measures cardiac repolarization, and prolongation is associated with adverse cardiovascular outcomes and death. The exponential Bazett correction formula overestimates the QT interval during tachycardia. OBJECTIVE: We evaluated 4 formulas of QT interval correction in individuals with sinus tachycardia for the identification of coronary artery disease, heart failure, and mortality. METHODS: The Penn Atrial Fibrillation Free study is a large cohort study of patients without atrial fibrillation. The present study examined 6723 Penn Atrial Fibrillation Free study patients without a history of heart failure and with baseline sinus rate >=100 beats/min. Medical records were queried for index clinical parameters, incident cardiovascular events, and all-cause mortality. The QT interval was corrected by using Bazett (QT/RR(0.5)), Fridericia (QT/RR(0.33)), Framingham [QT + 0.154 * (1000 - RR)], and Hodges (QT + 105 * (1/RR - 1)) formulas. RESULTS: In 6723 patients with a median follow-up of 4.5 years (interquartile range 1.9-6.4 years), the annualized cardiovascular event rate was 2.3% and the annualized mortality rate was 2.2%. QT prolongation was diagnosed in 39% of the cohort using the Bazett formula, 6.2% using the Fridericia formula, 3.7% using the Framingham formula, and 8.7% using the Hodges formula. Only the Hodges formula was an independent risk marker for death across the range of QT values (highest tertile: hazard ratio 1.26; 95% confidence interval 1.03-1.55). CONCLUSION: Although all correction formulas demonstrated an association between QTc values and cardiovascular events, only the Hodges formula identified one-third of individuals with tachycardia that are at higher risk of all-cause mortality. Furthermore, the Bazett correction formula overestimates the number of patients with a prolonged QT interval and was not associated with mortality. Future work may validate these findings and result in changes to automated algorithms for QT interval assessment. PMID- 26552755 TI - Dabigatran etexilate and reduction in serum apolipoprotein B. AB - OBJECTIVE: Carboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study. METHODS: 2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110 mg twice daily, dabigatran 150 mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis. RESULTS: From baseline to 3 months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (-0.057 (95% CI -0.069 to 0.044) g/L, p<0.001) and high-dose dabigatran (-0.065 (95% CI -0.078 to -0.053) g/L, p<0.001) but not warfarin (-0.006 g/L (95% CI -0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin. CONCLUSIONS: Dabigatran is associated with a significant (~7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes. PMID- 26552756 TI - Cost-effectiveness of percutaneous coronary intervention versus bypass surgery from a Dutch perspective. AB - AIMS: Recent cost-effectiveness analyses of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) have been limited by a short time horizon or were restricted to the US healthcare perspective. We, therefore, used individual patient-level data from the SYNTAX trial to evaluate the cost effectiveness of PCI versus CABG from a European (Dutch) perspective. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with three-vessel or left main coronary artery disease were randomised to either CABG (n=897) or PCI with drug eluting stents (DES; n=903). Costs were estimated for all patients based on observed healthcare resource usage over 5 years of follow-up. Health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5 year in-trial data to a lifetime horizon. Although initial procedural costs were lower for CABG, total initial hospitalisation costs per patient were higher (?17 506 vs ?14 037, p<0.001). PCI was more costly during the next 5 years of follow up, due to more frequent hospitalisations, repeat revascularisation procedures and higher medication costs. Nevertheless, total 5-year costs remained ?2465/patient higher with CABG. When the in-trial results were extrapolated to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with gains in both life expectancy and quality-adjusted life expectancy. The incremental cost-effectiveness ratio (ICER) (?5390/quality-adjusted life year (QALY) gained) was favourable and remained 90% of the bootstrap replicates. Outcomes were similar when incorporating the prognostic impact of non fatal myocardial infarction and stroke, as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. However, DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score <=22 or in those with left main disease. In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality, PCI was also economically dominant, whereas in those patients for whom the SYNTAX Score II favoured surgery, CABG was highly economically attractive (ICER range, ?2967 to ?3737/QALY gained). CONCLUSIONS: For the broad population with three-vessel or left main disease who are candidates for either CABG or PCI, we found that CABG is a clinically and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective. The cost-effectiveness of CABG versus PCI differed according to several anatomic factors, however. The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population, and may be a useful tool to guide resource allocation as well. TRIAL REGISTRATION NUMBER: Clinical trial unique identifier: NCT00114972 (http://www.clinical-trials.gov). PMID- 26552757 TI - The potential of point-of-care ultrasound by non-experts to improve diagnosis and patient care. PMID- 26552758 TI - Medical therapy, percutaneous coronary intervention and prognosis in patients with chronic total occlusions. AB - OBJECTIVE: There is little published data reporting outcomes for those found to have a chronic total coronary occlusion (CTO) that is electively treated medically versus those treated by percutaneous coronary intervention (PCI). We sought to compare long-term clinical outcomes between patients treated by PCI and elective medical therapy in a consecutive cohort of patients with an identified CTO. METHODS: Patients found to have a CTO on angiography between January 2002 and December 2007 in a single tertiary centre were identified using a dedicated database. Those undergoing CTO PCI and elective medical therapy to the CTO were propensity matched to adjust for baseline clinical and angiographic differences. RESULTS: In total, 1957 patients were identified, a CTO was treated by PCI in 405 (20.7%) and medical therapy in 667 (34.1%), 885 (45.2%) patients underwent coronary artery bypass graft surgery. Of those treated by PCI or medical therapy, propensity score matching identified 294 pairs of patients, PCI was successful in 177 patients (60.2%). All-cause mortality at 5 years was 11.6% for CTO PCI and 16.7% for medical therapy HR 0.63 (0.40 to 1.00, p=0.052). The composite of 5 year death or myocardial infarction occurred in 13.9% of the CTO PCI group and 19.6% in the medical therapy group, HR 0.64 (0.42 to 0.99, p=0.043). Among the CTO PCI group, if the CTO was revascularised by any means during the study period, 5-year mortality was 10.6% compared with 18.3% in those not revascularised in the medical therapy group, HR 0.50 (0.28-0.88, p=0.016). CONCLUSIONS: Revascularisation, but not necessarily PCI of a CTO, is associated with improved long-term survival relative to medical therapy alone. PMID- 26552759 TI - [Acute unilateral arteritic anterior ischemic optic neuropathy becoming bilateral despite corticosteroid therapy]. PMID- 26552760 TI - EphrinB2/EphA4-mediated activation of endothelial cells increases monocyte adhesion. AB - The membrane anchored ligand ephrinB2 belongs to the broad Eph/ephrin system and is able to activate different Eph receptors. The Eph receptors belong to the huge group of receptor-tyrosine kinases. Eph receptors as well as their corresponding ephrin ligands are cell-membrane attached proteins. Therefore, direct cell-cell contact is essentially for interaction. It is known that ephrinB2 plays a pivotal role in developmental and in tumour angiogenesis. Previous studies point to a crucial role of the EphA4-receptor in the process of monocyte adhesion. Since ephrinB2 is known as an interaction partner of EphA4, the aim of the present study was to investigate a possible interplay of EphA4-receptor with ephrinB2 during monocyte adhesion to the endothelium. As verified by bulk adhesion assays and atomic-force microscopy based single-cell force spectroscopy, temporary stimulation of endothelial cells from different sources with the soluble ligand ephrinB2 increased monocyte adhesion to endothelial cells. The proadhesive effect of ephrinB2 was independent of an active transcription, but is mediated via the Rho signaling pathway with subsequent modulation of the actin cytoskeleton. Furthermore, ephrinB2 mediated its impact on monocyte adhesion via the receptor EphA4 as shown by siRNA-mediated silencing. Interestingly, ephrinB2 was induced by TNF-alpha treatment. Silencing of ephrinB2 led to a lowering of the TNF-alpha mediated monocyte adhesion to endothelial cells. Furthermore, immunohistochemical staining of human atherosclerotic plaque revealed expression of ephrinB2 in macrophages. The results of the present study point to a crucial role of ephrinB2 induced EphA4 forward signaling in the context of monocyte adhesion to endothelial cells. This transcription-independent effect is mediated by Rho signaling induced actin-filament polymerization. PMID- 26552762 TI - Metabolism and lymphocyte biology. PMID- 26552761 TI - Genotype-specific regulation of oral innate immunity by T2R38 taste receptor. AB - The bitter taste receptor T2R38 has been shown to regulate mucosal innate immune responses in the upper airway epithelium. Furthermore, SNPs in T2R38 influence the sensitivity to 6-n-propylthiouracil (PROP) and are associated with caries risk/protection. However, no study has been reported on the role of T2R38 in the innate immune responses to oral bacteria. We hypothesize that T2R38 regulates oral innate immunity and that this regulation is genotype-specific. Primary gingival epithelial cells carrying three common genotypes, PAV/PAV (PROP super taster), AVI/PAV (intermediate) and AVI/AVI (non-taster) were stimulated with cariogenic bacteria Streptococcus mutans, periodontal pathogen Porphyromonas gingivalis or non-pathogen Fusobacterium nucleatum. QRT-PCR analyzed T2R38 mRNA, and T2R38-specific siRNA and ELISA were utilized to evaluate induction of hBD-2 (antimicrobial peptide), IL-1alpha and IL-8 in various donor-lines. Experiments were set up in duplicate and repeated three times. T2R38 mRNA induction in response to S. mutans was highest in PAV/PAV (4.3-fold above the unstimulated controls; p<0.05), while lowest in AVI/AVI (1.2-fold). In PAV/PAV, hBD-2 secretion in response to S. mutans was decreased by 77% when T2R38 was silenced. IL-1alpha secretion was higher in PAV/PAV compared to AVI/PAV or AVI/AVI with S. mutans stimulation, but it was reduced by half when T2R38 was silenced (p<0.05). In response to P. gingivalis, AVI/AVI showed 4.4-fold increase (p<0.05) in T2R38 expression, whereas the levels in PAV/PAV and AVI/PAV remained close to that of the controls. Secretion levels of IL-1alpha and IL-8 decreased in AVI/AVI in response to P. gingivalis when T2R38 was silenced (p<0.05), while the changes were not significant in PAV/PAV. Our data suggest that the regulation of gingival innate immunity by T2R38 is genotype-dependent and that the ability to induce a high level of hBD-2 by PAV/PAV carriers may be a reason for protection against caries in this group. PMID- 26552763 TI - Molecular epidemiology of carbapenem resistant Enterobacteriaceae in Valle d'Aosta region, Italy, shows the emergence of KPC-2 producing Klebsiella pneumoniae clonal complex 101 (ST101 and ST1789). AB - BACKGROUND: The spread of carbapenem resistant Enterobacteriaceae (CRE) is an emerging clinical problem, of great relevance in Europe and worldwide. The aim of this study was the molecular epidemiology of CRE isolates in Valle d'Aosta region, Italy, and the mechanism of carbapenem resistance. RESULTS: Sixty consecutive CRE samples were isolated from 52 hospital inpatients and/or outpatients from November 2013 to August 2014. Genotyping of microbial isolates was done by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST), carbapenemases were identified by PCR and sequencing. Carbapenem resistance gene transfer was performed by filter mating, plasmids from parental and transconjugant strains were assigned to incompatibility groups by PCR-based replicon typing. Molecular characterization of CRE isolates assigned 25 Klebsiella pneumoniae isolates to PFGE types A1-A5 and sequencing type (ST) 101, 17 K. pneumoniae isolates to PFGE type A and ST1789 (a single locus variant of ST101), 7 K. pneumoniae isolates to PFGE types B or C and ST512, 2 K. pneumoniae isolates to PFGE type D and ST405, and 5 Escherichia coli isolates to PFGE type a and ST131. All K. pneumoniae ST101 and ST1789 isolates were extended-spectrum beta-lactamase (ESBL) producers and carried bla CTX-M-1 group gene; 4 K. pneumoniae ST101 isolates were resistant to colistin. Molecular analysis of beta lactamase genes identified bla KPC-2 and bla CTX-M-group 1 into conjugative plasmid/s assigned to IncFII incompatibility group in ST101 and ST1789 K. pneumoniae isolates, bla KPC-3 into conjugative plasmid/s assigned to IncF incompatibility group in ST512 and ST405 K. pneumoniae isolates, bla VIM-1 into conjugative plasmid/s assigned to IncN incompatibility group in ST131 E. coli isolates. CONCLUSIONS: The spread of CRE in Valle d'Aosta region was caused by the selection of KPC-2 producing K. pneumoniae ST101 and ST1789 epidemic clones belonging to clonal complex 101, KPC-3 producing K. pneumoniae epidemic clones assigned to ST512 and ST405, and VIM-1 producing E.coli ST131 epidemic clone. Carbapenem resistance, along with bla KPC-2, bla KPC-3 and bla VIM-1 carbapenemase genes, was transferred by conjugative plasmids assigned to IncFII, IncF, and IncN incompatibility groups, respectively, in filter mating experiments. The emergence of colistin resistance was observed in KPC-2 producing K. pneumoniae ST101 isolates. PMID- 26552764 TI - Second-Line Chemotherapy for Metastatic Urothelial Carcinoma: Importance of Lymph Node-Only Metastasis as a Prognostic Factor and Construction of a Prognostic Model. AB - BACKGROUND: A prognostic model for patients with metastatic urothelial carcinoma (UC) progressing after platinum-based therapy was constructed from data from the phase III vinflunine trial. However, prognostic information for patients treated with other regimens is limited. MATERIALS AND METHODS: We pooled individual patient data from 7 second-line studies and analyzed the influence of factors of interest on overall survival (OS) through univariate and multivariate analysis. A prognostic model was constructed, and data from an independent series were used for validation. RESULTS: The data from 193 patients were pooled. The second-line chemotherapy regimen was single-agent taxane in 54 patients (28%), a platinum based combination in 47 (24%), and a non-platinum combination in 92 (48%). On multivariate analysis, Eastern Cooperative Oncology Group performance status >= 1, hemoglobin < 10 g/dL, and metastatic patterns other than lymph node-only metastasis emerged as independent adverse prognostic factors. Patients with all 3 factors (poor risk), 1 to 2 factors (intermediate risk), and no factors (good risk) had a median OS of 3.1, 8.7, and 16.5 months, respectively (P < .0001). The corresponding median OS for the validation series (n = 44) was 3.3, 8.1, and 13.3 months (P = .023). Furthermore, platinum-based regimens were independently associated with an OS benefit compared with other regimens (hazard ratio, 0.31; 95% confidence interval, 0.18-0.53; P < .0001). CONCLUSION: We have proposed and validated a prognostic model for patients with metastatic UC who were eligible for second-line therapy. The proposed model could prove helpful for risk stratification. Furthermore, our data suggest that testing second-line platinum based regimens in randomized trials is warranted. PMID- 26552765 TI - Stimulation with lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae maximizes cross-reactivity of anti-fungal T cells. AB - BACKGROUND AIMS: Invasive fungal diseases caused by filamentous fungi and yeasts are significant causes of morbidity and mortality in immunosuppressed hematology patients. We previously published a method to expand Aspergillus fumigatus specific T cells for clinical cell therapy. In the present study, we investigated expansion of T cells specific for other fungal pathogens and creation of a broadly reactive panfungal T-cell product. METHODS: Fungal strains selected were those frequently observed in the clinical hematology setting and included Aspergillus, Candida, Fusarium, Rhizopus and Lomentospora/Scedosporium. Four T cell cultures specific to each fungus were established. We selected lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae to expand panfungal T cells. Allelic restriction of anti-fungal activity was determined through the use of specific major histocompatibility complex class II-blocking antibodies. RESULTS: Individual T-cell cultures specific to each fungus could be expanded in vitro, generating predominantly CD4(+) T cells of which 8% to 20% were fungus specific. We successfully expanded panfungal T cells from the peripheral blood (n = 8) and granulocyte-colony-stimulating factor-primed stem cell products (n = 3) of normal donors by using a combination of lysates from Aspergillus terreus, Candida krusei and Rhizopus oryzae. Anti-fungal activity was mediated through human leukocyte antigen (HLA)-DR alleles and was maintained when antigen presenting cells from partially HLA-DRB1-matched donors were used to stimulate T cells. CONCLUSIONS: We demonstrate a method to manufacture panfungal T-cell products with specificity against a range of clinical fungal pathogens by use of the blood and stem cells of healthy donors as the starting material. The safety and efficacy of these products will need to be tested clinically. PMID- 26552766 TI - Novel bronchoscopic treatment for bronchopleural fistula using adipose-derived stromal cells. AB - BACKGROUND AIMS: In this report, we describe the successful bronchoscopic management of bronchopleural fistula in two patients, using autologous adipose derived stromal cells. Cell therapy was considered for 2 cases of bronchopleural fistula refractory to conventional surgical treatment after control of the primary disease was confirmed and active pleural infection was ruled out. Briefly, adipose-derived stem cells were first isolated from lipoaspirate and used without cell expansion. In 24 months, we have not received more patients with bronchopleural fistula in our hospital and we have not been able to include more patients. METHODS: Briefly, adipose-derived stem cells were first isolated from lipo-aspirate and used without cell expansion. A bronchopleural fistula was identified through bronchoscopy, and the mucosa surrounding the fistula was ablated with an argon plasma coagulator. Isolated stem cells were then endoscopically injected into the de-epithelialized area and fistulous tract. If an open thoracostomy was present at the time of the intervention, the same procedure was performed on the pleural side. Bronchoscopic follow-up was scheduled weekly during the first month, monthly during the first year, and then yearly. The underlying etiologies were left pneumonectomy and right lower video assisted lobectomy for non-small-cell lung cancer. The sizes of the fistulas were 6 mm and 3 mm in diameter, respectively. RESULTS: Both patients were discharged on the first postoperative day. The 3-year follow-up revealed a successful and maintained fistula closure, no treatment-related adverse reactions, nonlocal malignant recurrence and improved quality of life. CONCLUSIONS: This preliminary study showed that bronchoscopic application of autologous adipose-derived stem cells is a feasible, safe and effective procedure for treating bronchopleural fistula. PMID- 26552768 TI - Eosinophilic esophagitis. Preface. PMID- 26552767 TI - No up-regulation of the phosphatidylethanolamine N-methyltransferase pathway and choline production by sex hormones in cats. AB - BACKGROUND: Feline hepatic lipidosis (FHL) is a common cholestatic disease affecting cats of any breed, age and sex. Both choline deficiency and low hepatic phosphatidylethanolamine N-methyltransferase (PEMT) activity are associated with hepatic lipidosis (HL) in humans, mice and rats. The PEMT expression is known to be upregulated by oestrogens, protecting the females in these species from the development of HL when exposed to choline deficient diets. The aim of the present study was to evaluate the influence of sex hormones on choline synthesis via the PEMT pathway in healthy male and female cats before and after spaying/neutering, when fed a diet with recommended dietary choline content. RESULTS: From six female and six male cats PEMT activity was assayed directly in liver biopsies taken before and after spaying/neutering, and assessed indirectly by analyses of PEMT-specific hepatic phosphatidylcholine (PC) species and plasma choline levels. Hepatic PEMT activity did not differ between intact female and male cats and no changes upon spaying/neutering were observed. Likewise, no significant differences in liver PC content and PEMT-specific polyunsaturated PC species were found between the sexes and before or after spaying/neutering. CONCLUSION: These results suggest that choline synthesis in cats differs from what is observed in humans, mice and rats. The lack of evident influence of sex hormones on the PEMT pathway makes it unlikely that spaying/neutering predisposes cats for HL by causing PC deficiency as suggested in other species. PMID- 26552769 TI - The genetic basis of eosinophilic esophagitis. AB - Eosinophilic esophagitis is characterized by destructive responses of the immune system to environmental allergens, including food, on the human esophagus. EoE is now reported as a major cause of upper gastrointestinal morbidity in children and adults and the incidence is reported to be on the increase. It is known that EoE has a high degree of heritability, with a majority of the phenotypic variation believed to be genetic in origin as shown by genetic epidemiology studies of twins and families. Prior to 2010, there were no known genetic risk factors for the disease. Three GWAS have since been published identifying 5 loci which influence risk for EoE in both children and adults. The information gained from GWAS has been of value in elucidating the pathways involved, such as IL4/STAT6, and more unexpected pathways such as epithelial apical transport and wound healing. We will review the results of the EoE GWAS and the known associated genes, concluding with a discussion of some future directions for genetic studies in EoE. PMID- 26552770 TI - Allergic mechanisms of Eosinophilic oesophagitis. AB - Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and oesophageal eosinophilia refractory to proton-pump-inhibitor treatment. EoE is a food allergy, as elimination of food trigger(s) abrogates the disease, while trigger reintroduction causes recurrence. The allergic mechanism of EoE involves both IgE and non-IgE processes. There is a break in oral tolerance, the immune mechanism allowing enteric exposure to food and micro-organisms without causing deleterious immune responses. Changes in life-style, alterations in gut flora and use of antibiotics may be increasing disease prevalence. Mouse models of EoE and human studies revealed the role of regulatory T-cells and iNKT-cells in the pathogenesis. Th2-cytokines like IL-4, IL-5 and IL-13, and other cytokines like TGFbeta and TSLP are involved, but perhaps no one cytokine is critically important for driving the disease. Control of EoE may require a pharmaceutical approach that blocks more than one target in the Th2-inflammatory pathway. PMID- 26552772 TI - Insights into the emerging epidemic of eosinophilic oesophagitis. AB - Eosinophilic oesophagitis (EOE) is a relatively recently recognised condition characterised by an increase in oesophageal eosinophils. EOE occurs in children and adults with a strong male preponderance. There has been a sharp increase in EOE in North America, Europe and Australia. The reasons for this increase remain unclear but are likely to be influenced by genetic and environmental factors, as well as early-life exposures. Based on recent population-based data, the estimated EOE prevalence in the USA is 56.7 per 100,000 persons. The peak prevalence was observed in patients between 35 and 39 years of age. Prevalence figures in Asia and the Middle East generally appear to be lower than in Western countries, but population-based studies are not available. A causal association between coeliac disease and EOE appears unlikely. Data on the seasonal variation of EOE remain inconclusive. Further population-based studies are needed to define the epidemiology of EOE. PMID- 26552773 TI - Clinical features of Eosinophilic esophagitis in children and adults. AB - Eosinophilic esophagitis (EoE) may affect humans at any age with a predominance for Caucasian males. The clinical manifestation of EoE varies depending on the patient's age. Infants and young children may primarily present with unspecific symptoms such as feeding problems, vomiting and abdominal pain. In adolescents and adults, dysphagia and food impactation become the predominant symptoms. EoE should also be considered in cases of refractory heartburn in both children and adults. Concomitant allergic diseases such as asthma, rhinitis and eczema, as well as peripheral eosinophilia and elevated total serum IgE values are common in pediatric and adult EoE patients. EoE seems to be primarily a food antigen-driven disease, whereas in adults, aeroallergen sensitization may dominate. Endoscopic features of EoE include mucosal edema, furrows, exudates, corrugated rings, strictures, and the so-called crepe paper sign. There appears to be a shift from an inflammatory-predominant phenotype in young childhood towards a more fibrotic phenotype in adolescents and adults. Long-term follow studies suggest that EoE is a chronic and potentially progressive disease causing recurring dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of untreated disease, stressing the importance of early diagnosis and consequent treatment of EoE. PMID- 26552771 TI - Environmental and infectious factors in eosinophilic esophagitis. AB - Identifying possible environmental or infectious etiologic factors for eosinophilic esophagitis (EoE) may offer insight into opportunities for disease prevention and treatment. We reviewed the current literature to assess environmental and infectious factors evaluated in EoE. Few studies have been conducted, however a consistent inverse association between EoE and H. pylori has been described. Several studies suggest a weak association between season and EoE diagnosis, but the evidence is inconclusive. EoE has also been associated with early life factors, including Cesarean delivery and antibiotic use. Larger studies are needed to evaluate these associations more thoroughly. Several papers have speculated the potential for anti-secretory agents to contribute to EoE. This has not been formerly evaluated. In summary, there is significant opportunity in the future to advance our understanding of possible environmental etiologic factors for EoE. PMID- 26552774 TI - Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis. AB - Gastro-oesophageal reflux disease (GORD) is the most common oesophageal disorder, whereas eosinophilic oesophagitis (EoE) is an emerging disease unresponsive to PPI therapy. Updated guidelines in 2011 described proton pump inhibitor responsive esophageal eosinophilia (PPI-REE), a novel phenotype in EoE patients who were responsive to PPIs. This article aims to update the complex interplay between GORD, EoE and PPIs. Oesophageal mucosal integrity is diffusely impaired in EoE and PPI-REE patients. PPI-REE might occur with either normal or pathological pH monitoring. The genetic hallmark of EoE is overlapped in PPI-REE, but not in GORD. PPIs can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Acid hypersensitivity in EoE patients may explain symptomatic but not histological response on PPIs. Unsolved issues with PPI-REE are whether oesophageal barrier impairment is the cause or the effect of oesophageal eosinophilia and whether PPIs primarily targets barrier integrity or oesophageal inflammation. PMID- 26552775 TI - Disease associations in eosinophilic oesophagitis and oesophageal eosinophilia. AB - Eosinophilic infiltration into oesophageal tissue, typical of eosinophilic oesophagitis (EoE), has been described in several other conditions, including infections, hypersensitivity, and other autoimmune disorders. Since its description, EoE has been associated with an increasing number of diseases also characterized by tissue infiltration, including eosinophilic gastroenteritis and Crohn's disease. While an association between EoE and coeliac disease was previously reported, it is not supported by recent research. In contrast, EoE seems to be common in patients with a history of congenital oesophageal atresia, leading to hypotheses linking both disorders. The prevalence of EoE has also been shown to be eight times higher in patients with connective tissue disorders (CTDs), which has led to the proposal of an EoE-CTD phenotype, although this requires further assessment. This paper reviews the evidence of EoE's associations with several disorders, defining the common bases from an epidemiological, clinical, molecular and genetic perspective whenever possible. PMID- 26552777 TI - Diagnostic approach to eosinophilic oesophagitis: Pearls and pitfalls. AB - Eosinophilic oesophagitis (EoE) has first been described a little over 20 years ago. EoE has been defined by a panel of international experts as a "chronic, immune/antigen-mediated, oesophageal disease, characterized clinically by symptoms related to oesophageal dysfunction and histologically by eosinophil predominant inflammation". A value of >= 15 eosinophils has been defined as histologic diagnostic cutoff. Other conditions associated with oesophageal eosinophilia, such as gastro-oesophageal reflux disease (GERD), PPI-responsive oesophageal eosinophilia, or Crohn's disease should be excluded before EoE can be diagnosed. This review highlights the latest insights regarding the diagnosis and differential diagnosis of EoE. PMID- 26552776 TI - An allergist's perspective to the evaluation of Eosinophilic Esophagitis. AB - Eosinophilic Esophagitis (EoE) is a classic atopic disease as it shares features with other atopic disease on all levels including pathogenesis, genetics, epidemiology, and treatment options. EoE has elements of Th2 pathogenesis with increase levels of Th2 cytokines (IL4, 5, and 13). In addition, it shares atopic genetic risk factors including thymic stromal lymphopoietin (TSLP) loci as a risk factor in genome wide association studies. EoE patients have a higher rate of other atopic disease (asthma, allergic rhinitis and food allergy) compared to the general population indicating their atopic phenotype. Like asthma, atopic dermatitis or food allergy, EoE has increased in the last 20 years. Treatment options include the basic principle of other atopic diseases include using topical steroids or avoidance of the triggers (food or pollen). An allergist provides a critical role as they are experts in the treatment of atopic disease including avoidance strategies. PMID- 26552778 TI - Elimination and elemental diet therapy in eosinophilic oesophagitis. AB - Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disorder of the oesophagus. The incidence of EoE has been raised substantially and EoE has recently become the most prevalent cause of dysphagia among the adolescents. Food and aeroallergens are believed to play a major role in the pathogenesis. Current treatment includes topical steroids and dietary therapy. Dietary therapy with elimination of causative allergens could provide a durable long-term solution. Dietary therapy in EoE consists of in elemental and empiric elimination diets. Elemental diet with amino acid-based formula is most effective in achieving disease remission but poor taste makes adherence challenging. Empiric elimination diet based on avoidance of most common food allergens offers moderate response rates, the usefulness of allergy test-directed elimination diets is questioned by low response rates. In conclusion, dietary treatments for EoE seem promising, but further refinement is required before it can become standard care. PMID- 26552779 TI - Medical therapy in eosinophilic oesophagitis. AB - Eosinophilic oesophagitis (EoE) is a chronic-inflammatory disease of the oesophagus. If left untreated, eosinophilic inflammation induces fibrosis, angiogenesis and stricture formation, resulting finally in a so called remodelling with structural and functional damage of the organ. In addition, patients with untreated EoE are permanently at risk of experiencing food impactions. It is therefore widely accepted that active EoE should be treated. Any treatment applied in EoE should ideally achieve two therapeutic goals: first, resolution of symptoms, and, second, control of inflammation. Avoidance of food allergens by elimination diets as well as anti-inflammatory drugs have both the ability to achieve these goals. Among the pharmacological options, only corticosteroids have documented efficacy, whereas alternatives have shown rather disappointing results or are still under evaluation. Of note, swallowed topical corticosteroids are at least as efficient as systemically administered corticosteroids but have fewer side effects. As such topical corticosteroids are widely used as first-line drug in the treatment of EoE, even though this compound is currently not approved for this indication by regulatory authorities. Unfortunately, complete resolution of symptoms can be achieved with swallowed topical corticosteroids only in approximately 70% of patients despite appropriate dosing and despite correct administration of these compounds. Control of inflammation is even harder to achieve, as only in approximately 50% of patients tissue eosinophilia disappears completely under this anti-inflammatory medication. For this group of "difficult to treat" patients, therapeutic alternatives are urgently needed. Fortunately several anti-allergic drugs and several biologicals are currently under investigation. PMID- 26552780 TI - Esophageal dilation in eosinophilic esophagitis. AB - Tissue remodeling with scaring is common in adult EoE patients with long standing disease. This is the major factor contributing to their complaints of solid food dysphagia and recurrent food impactions. The best tests to define the degree of remodeling are barium esophagram, high resolution manometry and endoscopy. Many physicians are fearful to dilate EoE patients because of concerns about mucosal tears and perforations. However, multiple recent case series attest to the safety of esophageal dilation and its efficacy with many patients having symptom relief for an average of two years. This chapter will review the sordid history of esophageal dilation in EoE patients and outline how to perform this procedure safely. The key is graduated dilation over one to several sessions to a diameter of 15-18 mm. Postprocedural pain is to be expected and mucosal tears are a sign of successful dilation, not complications. In some healthy adults, occasional dilation may be preferred to regular use of medications or restricted diets. This approach is now supported by recent EoE consensus statements and societal guidelines. PMID- 26552781 TI - Therapeutic strategies in eosinophilic esophagitis: Induction, maintenance and refractory disease. AB - Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease that is increasingly recognized as one of the most common causes of dysphagia and foregut symptoms in adults and children. Topical corticosteroids, elimination diets, and esophageal dilations are effective options for both induction and maintenance therapy in EoE. Current pharmacologic options are being used off-label as no agent has yet been approved by regulatory authorities. Little is known about the natural history of EoE, however, raising controversy regarding the necessity of maintenance and therapy in asymptomatic or treatment-refractory patients. Furthermore, variability in treatment endpoints used in EoE clinical trials makes interpretation and comparability of EoE treatments challenging. Recent validation of a patient-related outcome (PRO) instruments, a histologic scoring tool, and an endoscopic grading system for EoE are significant advances toward establishing consistent treatment endpoints. PMID- 26552782 TI - Mid-term survival analysis of closed wedge high tibial osteotomy: A comparative study of computer-assisted and conventional techniques. AB - BACKGROUND: The purpose of the present study was to compare the clinical and radiographic results and survival rates between computer-assisted and conventional closing wedge high tibial osteotomies (HTOs). METHODS: Data from a consecutive cohort comprised of 75 computer-assisted HTOs and 75 conventional HTOs were retrospectively reviewed. The Knee Society knee and function scores, Hospital for Special Surgery (HSS) score and femorotibial angle (FTA) were compared between the two groups. Survival rates were also compared with procedure failure. RESULTS: The knee and function scores at one year postoperatively were slightly better in the computer-assisted group than those in conventional group (90.1 vs. 86.1) (82.0 vs. 76.0). The HSS scores at one year postoperatively were slightly better for the computer-assisted HTOs than those of conventional HTOs (89.5 vs. 81.8). The inlier of the postoperative FTA was wider in the computer assisted group than that in the conventional HTO group (88.0% vs. 58.7%), and mean postoperative FTA was greater in the computer-assisted group that in the conventional HTO group (valgus 9.0 degrees vs. valgus 7.6 degrees , p<0.001). The five- and 10-year survival rates were 97.1% and 89.6%, respectively. No difference was detected in nine-year survival rates (p=0.369) between the two groups, although the clinical and radiographic results were better in the computer-assisted group that those in the conventional HTO group. CONCLUSIONS: Mid-term survival rates did not differ between computer-assisted and conventional HTOs. A comparative analysis of longer-term survival rate is required to demonstrate the long-term benefit of computer-assisted HTO. LEVEL OF EVIDENCE: III. PMID- 26552783 TI - Anterior cruciate ligament injury: A persistently difficult diagnosis. AB - BACKGROUND: Historically anterior cruciate ligament (ACL) injuries have been diagnosed poorly. A paper published in Injury in 1996 showed that less than 10% of patients with an ACL injury had the diagnosis made by the first physician to see them and that the average delay from first presentation to diagnosis was 21 months. The aim of our study was to investigate whether an improvement has been made over the last two decades in diagnosing ACL injuries. METHODS: We identified 160 patients who had an ACL reconstruction performed by a single surgeon between October 2004 and December 2011 and for whom a complete data set was available. Data was extracted retrospectively from the hospital notes and a dedicated patient database. We performed a sub-group analysis comparing patients seen prior to the introduction of an acute knee injury clinic in April 2007 and patients seen after the introduction of the clinic. RESULTS: 75.1% (120/160) of patients presented first to an emergency department (ED) or to their general practitioner (GP), but only 14.4% (23/160) were diagnosed on initial presentation. The median number of healthcare professionals a patient saw prior to a diagnosis of ACL injury was 3. The median delay from injury to presentation was 0 weeks (range 0 885), injury to diagnosis 13 weeks (0-926), presentation to diagnosis 10 weeks (0 924), presentation to a specialist knee clinic 24 weeks (0-1006), and specialist knee clinic to surgery 13 weeks (0-102). The median total time from injury to surgery was 42 weeks (0-1047). Following the implementation of an acute knee injury clinic in 2007, the median delay from presentation to surgery dropped from 59 weeks to 36 weeks (p = 0.050) and there was a significant decrease in the median delay from specialist knee clinic to surgery from 23 to 11 weeks (p=0.002). CONCLUSION: Over the past two decades there appears to have been little improvement in the early diagnosis of ACL injuries, with only 14.4% of patients being diagnosed correctly at initial presentation. We recommend further education of emergency and primary care clinicians in the diagnosis of ACL injuries, emphasising the importance of the typical history of an ACL injury. The implementation of an acute knee injury clinic may help minimise delays to surgery, which should result in better patient outcomes. PMID- 26552784 TI - Optically detecting the edge-state of a three-dimensional topological insulator under ambient conditions by ultrafast infrared photoluminescence spectroscopy. AB - Ultrafast infrared photoluminescence spectroscopy was applied to a three dimensional topological insulator TlBiSe2 under ambient conditions. The dynamics of the luminescence exhibited bulk-insulating and gapless characteristics bounded by the bulk band gap energy. The existence of the topologically protected surface state and the picosecond-order relaxation time of the surface carriers, which was distinguishable from the bulk response, were observed. Our results provide a practical method applicable to topological insulators under ambient conditions for device applications. PMID- 26552785 TI - Exhausted implanted pulse generator in sacral nerve stimulation for faecal incontinence: What next in daily practice for patients? AB - PURPOSE: The efficacy of sacral nerve stimulation in faecal incontinence relies on an implanted pulse generator known to have a limited lifespan. The long-term use of sacral nerve stimulation raises concerns about the true lifespan of generators. The aim of the study was to assess the lifespan of sacral nerve stimulation implanted pulse generators in daily practice, and the outcome of exhausted generator replacement, in faecal incontinent patients. METHODS: Faecal incontinent patients with pulse generators (Medtronic InterstimTM or InterstimIITM) implanted in a single centre from 2001 to 2014 were prospectively followed up. Generator lifespan was measured according to the Kaplan-Meier method. Patients with a generator explanted/turned off before exhaustion were excluded. Morbidity of exhausted generator replacement and the outcome (Cleveland Clinic Florida Faecal Incontinence (CCF-FI) and Faecal Incontinence Quality of Life (FIQL) scores) were recorded. RESULTS: Of 135 patients with an implanted pulse generator, 112 (InterstimII 66) were included. Mean follow-up was 4.9 +/- 2.8 years. The generator reached exhaustion in 29 (26%) cases. Overall median lifespan of an implanted pulse generator was approximately 9 years (95% CI 8 9.2). Interstim and InterstimII 25th percentile lifespan was 7.2 (CI 6.4-8.3) and 5 (CI 4-not reached) years, respectively. After exhaustion, generators were replaced, left in place or explanted in 23, 2 and 4 patients, respectively. Generator replacement was virtually uneventful. CCF-FI/FIQL scores remained unchanged after generator replacement (CCF-FI 8 +/- 2 vs 7 +/- 3; FIQL 3 +/- 0.6 vs 3 +/- 0.5; p = ns). CONCLUSION: In this study, the implanted pulse generator observed median lifespan was 9 years. After exhaustion, generators were safely and efficiently replaced. The study also gives insight into long-term needs and costs of sacral nerve stimulation (SNS) therapy. PMID- 26552786 TI - Appropriate selection is essential for achieving satisfactory outcomes in laparoscopic colonic resections in emergency settings. PMID- 26552787 TI - Phosphinic acid-promoted addition reaction of isocyanides to (Z)-hydroximoyl chlorides: efficient synthesis of alpha-(hydroxyimino)amides. AB - The reaction of (Z)-hydroximoyl chlorides with isocyanides promoted by phosphinic acid in the presence of triethylamine proceeds smoothly to afford alpha (hydroxyimino)amides in good to high yields. Phosphinic acid plays an important role in effectively promoting the reaction. A wide range of (Z)-hydroximoyl chlorides and isocyanides were found to be suitable for this reaction. PMID- 26552788 TI - Study on the removal of elemental mercury from simulated flue gas by Fe2O3 CeO2/AC at low temperature. AB - Fe2O3 and CeO2 modified activated coke (AC) synthesized by the equivalent-volume impregnation were employed to remove elemental mercury (Hg(0)) from simulated flue gas at a low temperature. Effects of the mass ratio of Fe2O3 and CeO2, reaction temperature, and individual flue gas components including O2, NO, SO2, and H2O (g) on Hg(0) removal efficiency of impregnated AC were investigated. The samples were characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Results showed that with optimal mass percentage of 3 % Fe2O3 and 3 % CeO2 on Fe3Ce3/AC, the Hg(0) removal efficiency could reach an average of 88.29 % at 110 degrees C. Besides, it was observed that O2 and NO exhibited a promotional effect on Hg(0) removal, H2O (g) exerted a suppressive effect, and SO2 showed an insignificant inhibition without O2 to some extent. The analysis of XPS indicated that the main species of mercury on used Fe3Ce3/AC was HgO, which implied that adsorption and catalytic oxidation were both included in Hg(0) removal. Furthermore, the lattice oxygen, chemisorbed oxygen, and/or weakly bonded oxygen species made a contribution to Hg(0) oxidation. PMID- 26552789 TI - Ecological determinants of health: food and environment on human health. AB - Human health and diseases are determined by many complex factors. Health threats from the human-animal-ecosystems interface (HAEI) and zoonotic diseases (zoonoses) impose an increasing risk continuously to public health, from those emerging pathogens transmitted through contact with animals, food, water and contaminated environments. Immense challenges forced on the ecological perspectives on food and the eco-environments, including aquaculture, agriculture and the entire food systems. Impacts of food and eco-environments on human health will be examined amongst the importance of human interventions for intended purposes in lowering the adverse effects on the biodiversity. The complexity of relevant conditions defined as factors contributing to the ecological determinants of health will be illuminated from different perspectives based on concepts, citations, examples and models, in conjunction with harmful consequential effects of human-induced disturbances to our environments and food systems, together with the burdens from ecosystem disruption, environmental hazards and loss of ecosystem functions. The eco-health literacy should be further promoting under the "One Health" vision, with "One World" concept under Ecological Public Health Model for sustaining our environments and the planet earth for all beings, which is coincidentally echoing Confucian's theory for the environmental ethics of ecological harmony. PMID- 26552790 TI - Recycling of iron and silicon from drinking water treatment sludge for synthesis of magnetic iron oxide@SiO2 composites. AB - More attention has been paid to the deterioration of water bodies polluted by drinking water treatment sludge (DWTS) in recent years. It is important to develop methods to effectively treat DWTS by avoiding secondary pollution. We report herein a novel investigation for recovery of Si and Fe from DWTS, which are used for the synthesis of two iron oxide@SiO2 composites for adsorption of reactive red X-3B (RRX-3B) and NaNO2. The results show that Fe(3+) (acid leaching) and Si(4+) (basic-leaching) can be successfully recovered from roasted DWTS. Whether to dissolve Fe(OH)3 precipitation is the key point for obtaining Fe3O4 or gamma-Fe2O3 particles using the solvothermal method. The magnetic characteristics of Fe3O4@SiO2 (390.0 m(2) g(-1)) or Fe2O3@SiO2 (220.9 m(2) g(-1)) are slightly influenced by the coated porous SiO2 layer. Peaks of Fe-O stretching vibration (580 cm(-1)) and asymmetric Si-O-Si stretching vibrations (1080 cm(-1)) of Fe3O4@SiO2 indicate the successful coating of a thin silica layer (20-150 nm). The adsorption capacity of RRX-3B and NaNO2 by Fe3O4@SiO2 is better than that of Fe2O3@SiO2, and both composites can be recycled through an external magnetic field. This method is an efficient and environmentally friendly method for recycling DWTS. PMID- 26552791 TI - Application of a novel electrochemical sensor containing organo-modified sericite for the detection of low-level arsenic. AB - A simple cyclic voltammetry (CV) analytical method with organo-modified sericite for the working electrode was investigated to detect As(III) in an aquatic environment, and optimal conditions for the reliable measurement of trace amounts of As(III) were studied. A distinct, specific peak was clearly observed at 0.8 V due to the reduction of H3AsO4 to H3AsO3. The specific peak current of arsenic increased with increasing the concentration of As(III) and initially increased proportionally to the scan rates. However, it disappeared as the scan rate increased over 400 mV/s. Because the surface of the organo-modified sericite electrode rapidly became saturated with As(III) when the deposition time increased, an optimal deposition time was determined as 60 s. Pb(2+) had no significant influence on the peak signal of As(III), whereas it was reduced as the ratio of Cu/As increased. Considering the detection limit of arsenic (1 ppb), this system can be used to detect low levels of As(III) in water systems. PMID- 26552792 TI - Impact of the novel neonicotinoid insecticide Paichongding on bacterial communities in yellow loam and Huangshi soils. AB - Insecticides are widely sprayed in modern agriculture for ensuring the crop yield, which could also lead to contamination and insecticide residue in soils. Paichongding (IPP) is a novel neonicotinoid insecticide and was developed recently in China. Soil bacterial community, diversity, and community composition vary widely depending on environmental factors. As for now, little is known about bacterial species thriving, bacterial community diversity, and structure in IPP spraying soils. In present study, IPP degradation in yellow loam and Huangshi soils was investigated, and bacterial communities and diversity were examined in soil without IPP spray and with IPP spray through pyrosequencing of 16S ribosomal RNA (rRNA) gene amplicons. The degradation ratio of IPP at 60 days after treatment (DAT) reached 51.22 and 34.01 % in yellow loam and Huangshi soil, respectively. A higher richness of operational taxonomic units (OTUs) was found in yellow loam soil (867 OTUs) and Huangshi soil (762 OTUs) without IPP spray while OUTs were relatively low in IPP-spraying soils. The community composition also differed both in phyla and genus level between these two environmental conditions. Proteobacteria, Firmicutes, Planctomycetes, Chloroflexi, Armatimonadetes, and Chlorobi were stimulated to increase after IPP application, while IPP inhibited the phyla of Bacteroidetes, Actinobacteria, and Acidobacteria. PMID- 26552793 TI - Glyphosate input modifies microbial community structure in clear and turbid freshwater systems. AB - Since it was commercially introduced in 1974, glyphosate has been one of the most commonly used herbicides in agriculture worldwide, and there is growing concern about its adverse effects on the environment. Assuming that glyphosate may increase the organic turbidity of water bodies, we evaluated the effect of a single application of 2.4 +/- 0.1 mg l(-1) of glyphosate (technical grade) on freshwater bacterioplankton and phytoplankton (pico, micro, and nanophytoplankton) and on the physical and chemical properties of the water. We used outdoor experimental mesocosms under clear and oligotrophic (phytoplanktonic chlorophyll a = 2.04 MUg l(-1); turbidity = 2.0 NTU) and organic turbid and eutrophic (phytoplanktonic chlorophyll a = 50.3 MUg l(-1); turbidity = 16.0 NTU) scenarios. Samplings were conducted at the beginning of the experiment and at 1, 8, 19, and 33 days after glyphosate addition. For both typologies, the herbicide affected the abiotic water properties (with a marked increase in total phosphorus), but it did not affect the structure of micro and nanophytoplankton. In clear waters, glyphosate treatment induced a trend toward higher bacteria and picoeukaryotes abundances, while there was a 2 to 2.5-fold increase in picocyanobacteria number. In turbid waters, without picoeukaryotes at the beginning of the experiment, glyphosate decreased bacteria abundance but increased the number of picocyanobacteria, suggesting a direct favorable effect. Moreover, our results show that the impact of the herbicide was observed in microorganisms from both oligo and eutrophic conditions, indicating that the impact would be independent of the trophic status of the water body. PMID- 26552795 TI - What Cure Models Can Teach us About Genome-Wide Survival Analysis. AB - The aim of logistic regression is to estimate genetic effects on disease risk, while survival analysis aims to determine effects on age of onset. In practice, genetic variants may affect both types of outcomes. A cure survival model analyzes logistic and survival effects simultaneously. The aim of this simulation study is to assess the performance of logistic regression and traditional survival analysis under a cure model and to investigate the benefits of cure survival analysis. We simulated data under a cure model and varied the percentage of subjects at risk for disease (cure fraction), the logistic and survival effect sizes, and the contribution of genetic background risk factors. We then computed the error rates and estimation bias of logistic, Cox proportional hazards (PH), and cure PH analysis, respectively. The power of logistic and Cox PH analysis is sensitive to the cure fraction and background heritability. Our results show that traditional Cox PH analysis may erroneously detect age of onset effects if no such effects are present in the data. In the presence of genetic background risk even the cure model results in biased estimates of both the odds ratio and the hazard ratio. Cure survival analysis takes cure fractions into account and can be used to simultaneously estimate the effect of genetic variants on disease risk and age of onset. Since genome-wide cure survival analysis is not computationally feasible, we recommend this analysis for genetic variants that are significant in a traditional survival analysis. PMID- 26552794 TI - Disturbance effects of PM10 on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid. AB - Myocardial infarction is the acute condition of myocardial necrosis that occurs as a result of imbalance between coronary blood supply and myocardial demand. Air pollution increases the risk of death from cardiovascular diseases (CVDs). The aim of this study was to investigate the effects of particulate matter (PM) on oxidative stress, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) level induced by ischemia-reperfusion injury, and the protective effects of vanillic acid (VA) in the isolated rat heart. Male Wistar rats were randomly divided into eight groups (n = 10), namely control, VAc, sham, VA, PMa (0.5 mg/kg), PMb (2.5 mg/kg), PMc (5 mg/kg), and PMc + VA groups. Particles with an aerodynamic diameter <10 MUm (PM10) was instilled into the trachea through a fine intubation tube. Two days following the PM10 instillation, the animal's hearts were isolated and transferred to a Langendorff apparatus. The hearts were subjected to 30 min of global ischemia followed by 60 min of reperfusion. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), xanthine oxidase (XOX), and lactate dehydrogenase (LDH) were measured using special kits. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine levels of iNOS and eNOS mRNA. An increase in left ventricular end-diastolic pressure (LVEDP), S-T elevation, and oxidative stress in PM10 groups was observed. Ischemia-reperfusion (I/R) induction showed a significant augment in the expression of iNOS mRNA level and a significant decrease in the expression eNOS mRNA level. This effect was more pronounced in the PM groups than in the control and sham groups. Vanillic acid caused a significant decrease in LVEDP, S-T elevation, and also a significant difference in eNOS mRNA expression level, antioxidant enzymes, iNOS mRNA expression level, and oxidative stress occurred on myocardial dysfunction after I/R in isolated rat hearts. This study showed that PM10 exposure had devastating effects on the myocardial heart, oxidative stress, and eNOS and iNOS mRNA expression levels. Vanillic acid was able to improve these parameters. Vanillic acid as a potent antioxidant could also provide protection against particulate matter-induced toxicity. PMID- 26552796 TI - In vivo investigation to the macrolide-glycosylating enzyme pair DesVII/DesVIII in Saccharopolyspora erythraea. AB - Glycosyltransferase DesVII and its auxiliary partner DesVIII from Streptomyces venezulae, homologs of EryCIII and EryCII in Saccharopolyspora erythraea, have previously been demonstrated to be flexible on their substrates in vitro. Herein, we investigated their in vivo function by interspecies complementation in the mutant strains of Sac. erythraea A226. As desVII and desVIII were concomitantly expressed in the DeltaeryCIII mutant, the erythromycin A (Er-A) production was restored. Interestingly, co-expression of desVII and desVIII in the DeltaeryBV mutant exhibited an increased Er-A yield by 15 % in comparison to A226. Hence, DesVII/DesVIII not only replaced EryCIII to upload D-desosamine to C5 position of 3-O-mycarosyl erythronolide B (MEB) but also in vivo attached L-mycarose, not D desosamine to C3 position of erythronolide B (EB) with a higher activity than EryBV. Furthermore, expression of desVII in DeltaeryCIII and DeltaeryBV-CIII partially restored the Er-A production; however, no Er-A was detected while desVII was expressed in DeltaeryBV. It was implicated that DesVII coupled with EryCII to form the DesVII/EryCII complex for attaching above two deoxysugars in the absence of EryCIII in Sac. erythraea. In addition, when desVII and desVIII were co-expressed in DeltaeryBV-CII, Er-A was recovered with a lower yield than DeltaeryBV-CIII. Our study presents an opportunity with Sac. erythraea as a cell factory for macrolide glycodiversification. PMID- 26552797 TI - Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins. AB - The glutarimide-containing polyketides represent a fascinating class of natural products that exhibit a multitude of biological activities. We have recently cloned and sequenced the biosynthetic gene clusters for three members of the glutarimide-containing polyketides-iso-migrastatin (iso-MGS) from Streptomyces platensis NRRL 18993, lactimidomycin (LTM) from Streptomyces amphibiosporus ATCC 53964, and cycloheximide (CHX) from Streptomyces sp. YIM56141. Comparative analysis of the three clusters identified mgsA and chxA, from the mgs and chx gene clusters, respectively, that were predicted to encode the PimR-like Streptomyces antibiotic regulatory proteins (SARPs) but failed to reveal any regulatory gene from the ltm gene cluster. Overexpression of mgsA or chxA in S. platensis NRRL 18993, Streptomyces sp. YIM56141 or SB11024, and a recombinant strain of Streptomyces coelicolor M145 carrying the intact mgs gene cluster has no significant effect on iso-MGS or CHX production, suggesting that MgsA or ChxA regulation may not be rate-limiting for iso-MGS and CHX production in these producers. In contrast, overexpression of mgsA or chxA in S. amphibiosporus ATCC 53964 resulted in a significant increase in LTM production, with LTM titer reaching 106 mg/L, which is five-fold higher than that of the wild-type strain. These results support MgsA and ChxA as members of the SARP family of positive regulators for the iso-MGS and CHX biosynthetic machinery and demonstrate the feasibility to improve glutarimide-containing polyketide production in Streptomyces strains by exploiting common regulators. PMID- 26552798 TI - Combination of phenylpyruvic acid (PPA) pathway engineering and molecular engineering of L-amino acid deaminase improves PPA production with an Escherichia coli whole-cell biocatalyst. AB - In our previous study, we produced phenylpyruvic acid (PPA) in one step from L phenylalanine by using an Escherichia coli whole-cell biocatalyst expressing an L amino acid deaminase (L-AAD) from Proteus mirabilis KCTC2566. However, the PPA titer was low due to the degradation of PPA and low substrate specificity of L AAD. In this study, metabolic engineering of the L-phenylalanine degradation pathway in E. coli and protein engineering of L-AAD from P. mirabilis were performed to improve the PPA titer. First, three aminotransferase genes were knocked out to block PPA degradation, which increased the PPA titer from 3.3 +/- 0.2 to 3.9 +/- 0.1 g/L and the substrate conversion ratio to 97.5 %. Next, L-AAD was engineered via error-prone polymerase chain reaction, followed by site saturation mutation to improve its catalytic performance. The triple mutant D165K/F263M/L336M produced the highest PPA titer of 10.0 +/- 0.4 g/L, with a substrate conversion ratio of 100 %, which was 3.0 times that of wild-type L-AAD. Comparative kinetics analysis showed that compared with wild-type L-AAD, the triple mutant had higher substrate-binding affinity and catalytic efficiency. Finally, an optimal fed-batch biotransformation process was developed to achieve a maximal PPA titer of 21 +/- 1.8 g/L within 8 h. This study developed a robust whole-cell E. coli biocatalyst for PPA production by integrating metabolic and protein engineering, strategies that may be useful for the construction of other biotransformation biocatalysts. PMID- 26552799 TI - Site localization of painful lesions during radiofrequency ablation of pulmonary veins using circular multi-electrode catheters. AB - PURPOSE: Previous data showed that pain sensation was common during pulmonary vein isolation (PVI) using an 8-mm radiofrequency (RF) ablation catheter. Pain was more common in the left pulmonary veins (PVs). We characterized the location of pain during PVI using circular multi-electrode ablation catheters. METHODS: Included are all consecutive patients with atrial fibrillation (AF) who underwent PVI using the phased RF PVAC(r) catheter (Medtronic) or the irrigated nMARQTM catheter (Biosense Webster) under conscious sedation between July 2011 and March 2015. Site of pain reaction was marked for each patient. RESULTS: A total of 251 patients (141 PVAC(r), 110 nMARQTM) were studied; 214 (85 %) had at least one lesion associated with pain. Gender (r = 0.084, p = 0.186), type of AF (r = 0.048, p = 0.452), age (r = 0.078, p = 0.216), and repeat procedure (r = 0.018, p = 0.78) were not correlated with pain. There was no association between site of pain and catheter type; only 33% of the painful PVs were also the largest ones (p = 0.5, kappa = 0.03, R = -0.083). One-year freedom from AF was similar for patients with and without painful PVs (p = 0.6). The distribution of pain was as follows: 126 (59%) left superior PV (LSPV), 28 (13%) left inferior, 28 (13%) all PVs, 12 (5.6%) right superior, 12 (5.6%) right inferior, 18 (8.4%) left common, and 2 (0.9%) right common PV. CONCLUSIONS: PVI using multi-electrode catheters more commonly caused pain sensation in LSPV. There was no influence of catheter type or PV size on pain localization. Our findings, which are similar to those using an 8-mm ablation catheter, imply that location of pain is not catheter dependent but rather a reflection of autonomic physiology. PMID- 26552800 TI - Functional neuroimaging of extraversion-introversion. AB - Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits. PMID- 26552802 TI - Pearls: How to Remove a Ceramic Liner From a Well-fixed Acetabular Component. PMID- 26552803 TI - CORR Insights((r)): What Are the 30-day Readmission Rates Across Orthopaedic Subspecialties? PMID- 26552801 TI - Dissecting the hypothalamic pathways that underlie innate behaviors. AB - Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed. PMID- 26552804 TI - Does Chronic Corticosteroid Use Increase Risks of Readmission, Thromboembolism, and Revision After THA? AB - BACKGROUND: Systemic corticosteroids are commonly used to treat autoimmune and inflammatory diseases, but they can be associated with various musculoskeletal problems and disorders. There currently is a limited amount of data describing the postoperative complications of THA associated specifically with chronic corticosteroid use. QUESTIONS/PURPOSES: For chronic corticosteroid users undergoing THA, we asked: (1) What is the risk of hospital readmission at 30 and 90 days after surgery? (2) What is the risk of venous thromboembolism at 30 and 90 days after surgery? (3) What is the risk of revision hip arthroplasty at 12 and 24 months after surgery? METHODS: We identified patients in the Statewide Planning and Research Cooperative System who underwent primary THA between January 2003 and December 2010. This database provides hospital discharge abstracts for all admissions in the state of New York each year. We used propensity scores to three-to-one match the 402 chronic corticosteroid users with a comparison cohort of 1206 patients according to age, sex, race, comorbidity score, year of surgery, and hip osteonecrosis. The risk of each outcome was compared between chronic corticosteroid users and the matched cohort. Because multiple comparisons were made, we considered p less than 0.008 as statistically significant. RESULTS: Readmission was more common for corticosteroid users at 30 days (odds ratio [OR], 1.45; 95% CI, 1.14-1.85; p = 0.003) and 90 days (OR, 1.37; 95% CI, 1.09-1.73; p = 0.007). Venous thromboembolism was not more frequent in corticosteroid users at 30 days (OR, 2.39; 95% CI, 1.08-5.26; p = 0.031) or 90 days (OR, 1.91; 95% CI, 1.03-3.53; p = 0.039). Revision arthroplasty was more common in corticosteroid users at 12 months (OR, 2.49; 95% CI, 1.35-4.59; p = 0.004), but not 24 months (OR, 2.04; 95% CI, 1.19-3.50; p = 0.010). CONCLUSIONS: After THA, chronic corticosteroid use is associated with an increased risk of readmission at 30 and 90 days and revision hip arthroplasty at 12 months in corticosteroid users. Patients and providers should discuss these risks before surgery. Insurers should consider incorporating chronic corticosteroid use as a comorbidity in bundled payments for THA, since this patient population is more likely to return to their provider for care during the postoperative period. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26552805 TI - Editor's Spotlight/Take 5: High Rates of Interest in Sex in Patients With Hip Arthritis. PMID- 26552806 TI - Do Orthopaedic Surgeons Acknowledge Uncertainty? AB - BACKGROUND: Much of the decision-making in orthopaedics rests on uncertain evidence. Uncertainty is therefore part of our normal daily practice, and yet physician uncertainty regarding treatment could diminish patients' health. It is not known if physician uncertainty is a function of the evidence alone or if other factors are involved. With added experience, uncertainty could be expected to diminish, but perhaps more influential are things like physician confidence, belief in the veracity of what is published, and even one's religious beliefs. In addition, it is plausible that the kind of practice a physician works in can affect the experience of uncertainty. Practicing physicians may not be immediately aware of these effects on how uncertainty is experienced in their clinical decision-making. QUESTIONS/PURPOSES: We asked: (1) Does uncertainty and overconfidence bias decrease with years of practice? (2) What sociodemographic factors are independently associated with less recognition of uncertainty, in particular belief in God or other deity or deities, and how is atheism associated with recognition of uncertainty? (3) Do confidence bias (confidence that one's skill is greater than it actually is), degree of trust in the orthopaedic evidence, and degree of statistical sophistication correlate independently with recognition of uncertainty? METHODS: We created a survey to establish an overall recognition of uncertainty score (four questions), trust in the orthopaedic evidence base (four questions), confidence bias (three questions), and statistical understanding (six questions). Seven hundred six members of the Science of Variation Group, a collaboration that aims to study variation in the definition and treatment of human illness, were approached to complete our survey. This group represents mainly orthopaedic surgeons specializing in trauma or hand and wrist surgery, practicing in Europe and North America, of whom the majority is involved in teaching. Approximately half of the group has more than 10 years of experience. Two hundred forty-two (34%) members completed the survey. We found no differences between responders and nonresponders. Each survey item measured its own trait better than any of the other traits. Recognition of uncertainty (0.70) and confidence bias (0.75) had relatively high Cronbach alpha levels, meaning that the questions making up these traits are closely related and probably measure the same construct. This was lower for statistical understanding (0.48) and trust in the orthopaedic evidence base (0.37). Subsequently, combining each trait's individual questions, we calculated a 0 to 10 score for each trait. The mean recognition of uncertainty score was 3.2 +/- 1.4. RESULTS: Recognition of uncertainty in daily practice did not vary by years in practice (0-5 years, 3.2 +/- 1.3; 6-10 years, 2.9 +/- 1.3; 11-20 years, 3.2 +/- 1.4; 21-30 years, 3.3 +/- 1.6 years; p = 0.51), but overconfidence bias did correlate with years in practice (0-5 years, 6.2 +/- 1.4; 6-10 years, 7.1 +/- 1.3; 11-20 years, 7.4 +/- 1.4; 21-30 years, 7.1 +/- 1.2 years; p < 0.001). Accounting for a potential interaction of variables using multivariable analysis, less recognition of uncertainty was independently but weakly associated with working in a multispecialty group compared with academic practice (beta regression coefficient, -0.53; 95% confidence interval [CI], -1.0 to -0.055; partial R(2), 0.021; p = 0.029), belief in God or any other deity/deities (beta, -0.57; 95% CI, -1.0 to -0.11; partial R(2), 0.026; p = 0.015), greater confidence bias (beta, 0.26; 95% CI, -0.37 to -0.14; partial R(2), 0.084; p < 0.001), and greater trust in the orthopaedic evidence base (beta, -0.16; 95% CI, -0.26 to -0.058; partial R(2), 0.040; p = 0.002). Better statistical understanding was independently, and more strongly, associated with greater recognition of uncertainty (beta, 0.25; 95% CI, 0.17-0.34; partial R(2), 0.13; p < 0.001). Our full model accounted for 29% of the variability in recognition of uncertainty (adjusted R(2), 0.29). CONCLUSIONS: The relatively low levels of uncertainty among orthopaedic surgeons and confidence bias seem inconsistent with the paucity of definitive evidence. If patients want to be informed of the areas of uncertainty and surgeon-to-surgeon variation relevant to their care, it seems possible that a low recognition of uncertainty and surgeon confidence bias might hinder adequately informing patients, informed decisions, and consent. Moreover, limited recognition of uncertainty is associated with modifiable factors such as confidence bias, trust in orthopaedic evidence base, and statistical understanding. Perhaps improved statistical teaching in residency, journal clubs to improve the critique of evidence and awareness of bias, and acknowledgment of knowledge gaps at courses and conferences might create awareness about existing uncertainties. LEVEL OF EVIDENCE: Level 1, prognostic study. PMID- 26552808 TI - [Knowledge achieves safety!]. PMID- 26552807 TI - Improving rates of maternal immunization: Challenges and opportunities. AB - OBJECTIVES: An increasing number of vaccines are recommended or are being developed for use during pregnancy to protect women, fetuses, and/or newborns. For vaccines that are already recommended, vaccine uptake is variable and well below desired target. We reviewed the literature related to factors that affect a healthcare provider's recommendation and a woman's willingness to be vaccinated during pregnancy. DESIGN: A scoping review of published literature from 2005 to 2015 was undertaken and all relevant articles were abstracted, summarized, and organized thematically. RESULTS: Barriers and facilitators were identified that either decreased or increased the likelihood of a healthcare provider offering and a pregnant woman accepting vaccination during pregnancy. Concern about the safety of vaccines given during pregnancy was the most often cited barrier among both the public and healthcare providers. Other barriers included doubt about the effectiveness of the vaccine, lack of knowledge about the burden of disease, and not feeling oneself to be at risk of the infection. Major facilitators for maternal immunization included specific safety information about the vaccine in pregnant women, strong national recommendations, and healthcare providers who both recommended and provided the vaccine to their patients. Systems barriers such as inadequate facilities and staffing, vaccine purchase and storage, and reimbursement for vaccination were also cited. Evidence-based interventions were few, and included text messaging reminders, chart reminders, and standing orders. CONCLUSIONS: In order to have an effective vaccination program, improvements in the uptake of recommended vaccines during pregnancy are needed. A maternal immunization platform is required that normalizes vaccination practice among obstetrical care providers and is supported by basic and continuing education, communication strategy, and a broad range of research. PMID- 26552809 TI - Prognostic significance of ST3GAL-1 expression in patients with clear cell renal cell carcinoma. AB - BACKGROUND: Aberrant sialylated carbohydrate synthesis is frequently noted in various cancers. Sialyltransferase ST3GAL-1, which adds a sialic acid in an alpha 2,3 linkage to Gal beta1,3 GalNAc, preforms an important role in modulating cellular behaviors. However, little is known about prognostic significance of ST3GAL-1 in clear cell renal cell carcinoma (ccRCC). In this study, we aimed to investigate the prognostic significance of sialyltransferase ST3GAL-1 and its correlation with clinical outcomes in patients with ccRCC. METHODS: A total of 286 patients who underwent nephrectomy between 2005 and 2007 in a single academic center were recruited. Immunohistochemical staining was performed on tissue microarrays to assess the expression level. Kaplan-Meier method and Cox proportional hazard model were applied to assess the prognostic value of ST3GAL 1. Nomograms were generated as prediction model for overall survival and disease free survival at 5 and 8 years after nephrectomy. RESULTS: The present results show high expression of ST3GAL-1 is associated with reduced overall survival (p = 0.013) and disease free survival (p = 0.004). In multivariate cox analyses, ST3GAL-1 was defined as an independent prognostic factor for overall survival (p = 0.006) and disease free survival (p = 0.001). After incorporation into the University of California Integrated Staging System (UISS) intermediate/high risk group for non-metastatic ccRCC, ST3GAL-1 could further distinguish patient with dismal prognosis (p = 0.015 and 0.002 for OS and DFS respectively). The nomograms revealed better predictive accuracy in predicting 5- and 8- year overall survival and disease free survival than the TNM stage alone. CONCLUSIONS: ST3GAL-1 is an independent adverse prognostic factor for recurrence and survival of patients with ccRCC. PMID- 26552810 TI - Egicoccus halophilus gen. nov., sp. nov., a halophilic, alkalitolerant actinobacterium and proposal of Egicoccaceae fam. nov. and Egicoccales ord. nov. AB - A novel Gram-stain-positive, non-motile, moderately halophilic and alkalitolerant actinobacterium, designated EGI 80432T, was isolated from a saline-alkaline soil of Xinjiang province, north-west China. Cells were non-endospore-forming cocci with a diameter of 0.5-0.8 MUm. Strain EGI 80432T grew in the presence of 0-9 % (w/v) NaCl (optimum at 3-5 %), and also grew within the pH range 6.0-10.0 (optimum at pH 8.0-9.0) on marine 2216E medium. The peptidoglycan type was A1gamma. The whole-cell hydrolysates contained glucose, galactose, mannose and three unknown sugars as major sugars. The predominant menaquinone was MK-9(H4). The major fatty acids were C17 : 1omega8c, summed feature 3 (C16 : 1omega7c/C16 : 1omega6c), C18 : 1omega9c and iso-C15 : 0 The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, one unknown phosphoglycolipid, three unknown phospholipids and four unknown polar lipids. The genomic DNA G+C content was 75.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EGI 80432T clustered within the radius of the class Nitriliruptoria. Levels of sequence similarity between strain EGI 80432T and its phylogenetic neighbours Nitriliruptor alkaliphilus ANL-iso2T and Euzebya tangerina F10T were 94.1 and 88.1 %, respectively. Based on morphological, physiological and chemotaxonomic characteristics and phylogenetic analysis, a novel species of a new genus, Egicoccus halophilus gen. nov., sp. nov., is proposed, within the new family and new order Egicoccaceae fam. nov. and Egicoccales ord. nov. in the class Nitriliruptoria. The type strain of Egicoccus halophilus is EGI 80432T ( = CGMCC 1.14988T = KCTC 33612T). PMID- 26552811 TI - Prenatal diagnosis of Fraser syndrome: a matter of life or death? AB - BACKGROUND: Fraser Syndrome is a rare, autosomal recessive syndrome. It's characterized primarily by cryptophthalmos, syndactyly and urogenital malformation. Respiratory malformations are frequently present and not taken into account. To better manage childbirth at the time of delivery it is crucial to get prenatal diagnosis early on in the pregnancy. CASE PRESENTATION: We are reporting a female infant born by natural birth with 46,XX. She was characterized phenotypically by cryptophthalmos, syndactyly, bilateral microtia and ambiguous genitalia. A prenatal ultrasound didn't revealed or raised any suspects for the Fraser Syndrome. It only discovered a unilateral kidney agenesis. At birth the infant showed a severe respiratory distress, intubation was attempted but it failed. The baby was transferred to Santobono-Pausilipon III level hospital. A tracheostomy was performed successfully and saved her life. Computerized Tomography revealed left microphthalmos and a malformation like-coloboma into right ocular globe with cysts and a small calcification parietal anterior. Genetic test revealed the typical mutations in the gene FREM2 confirming the diagnosis of Fraser Syndrome. In her fourth month, after birth, the infant was subjected to an operation to reconstruct eyelids with a mucous membrane graft. The left renal function was normal. The baby showed a delay in motor milestones for visual impairment. At the 19(th) month fallow-up, during a magnetic resonance it was revealed: a normal morphologic brain development, a thin presence in the right optic nerve and the visual cortex were developing. CONCLUSIONS: The prenatal diagnosis of Fraser Syndrome is frequently possible. The prenatal ultrasound can reveal features like polyhydramnios or oligohydramnios, echogenic lungs, renal abnormalities or agenesis and cryptophthalmos that are pathognomonic of the Fraser Syndrome. The health providers must keep in mind that if there are suspects of the Fraser Syndrome during prenatal exams, the infants could have a severe malformation in the respiratory tract. PMID- 26552812 TI - Selection of Aptamers for Metabolite Sensing and Construction of Optical Nanosensors. AB - Optical nanosensors are based on particles with diameters from 20 to 200 nm containing sensory elements. The latter are comprised of one or more signaling molecules and one or more references, which allow measurements to be ratiometric and hence independent on the amount of sensor. The signaling molecules may range from simple ion-binding fluorophores, e.g., pH-sensitive dyes, to complex biochemical assays. Aptamers are ideal for use in nanosensors because they are relatively easy to modify chemically and hence to transform into signaling molecules, and their binding affinities may be fine-tuned to a desired measuring range in the selection process. Here we first describe the selection of metabolite binding aptamers, how they are transformed into signaling molecules using a molecular beacon construct and then how they are inserted into nanoparticles. Finally, we briefly describe how the sensors are calibrated before inserted into cells to measure metabolite concentration in real time. As examples we present aptamers binding to key metabolites in cells: ATP and fructose 1, 6 bisphosphate (FBP). PMID- 26552813 TI - SELEX of Cell-Specific RNA Aptamers. AB - This chapter focuses on the selection of RNA aptamers, which bind to specific cell surface components and thus can be internalized receptor mediated. Such aptamers discriminate between different tissues, e.g., detect malignant cells, and target them or induce apoptosis through drug internalization. However, before starting the selection process the choice of an ideal target can be challenging. To give an example for the selection of cell specific aptamers, we here used the interleukin-6 receptor (IL-6R) as a target, which is presented on hepatocytes, neutrophils, monocytes, and macrophages. PMID- 26552814 TI - Developing Aptamers by Cell-Based SELEX. AB - The reliable targeting of cell surface disease-associated proteins is a major challenge in chemical biology and molecular medicine. In this regard, aptamers represent a very attractive and innovative class of ligand molecules. Aptamers are generated by a reiterated in vitro procedure, named SELEX (Systematic Evolution of Ligands by Exponential enrichment). In order to generate aptamers for heavily modified cell surface-bound proteins and transmembrane receptors, the SELEX procedure has been recently adapted to the use of living cells as complex targets (referred as "cell-SELEX"). Here we give an overview on the most recent advances in the field of cell-SELEX technology, providing a detailed description of the differential cell-SELEX approach that has been developed in our laboratory to identify specific signatures for human malignant glioma and non-small-cell lung cancer. The procedures used for the evaluation of binding specificity and for the preliminary identification of potential target receptors will be also described. PMID- 26552815 TI - DNA Aptamer Generation by Genetic Alphabet Expansion SELEX (ExSELEX) Using an Unnatural Base Pair System. AB - Genetic alphabet expansion of DNA using unnatural base pair systems is expected to provide a wide variety of novel tools and methods. Recent rapid progress in this area has enabled the creation of several types of unnatural base pairs that function as a third base pair in polymerase reactions. Presently, a major topic is whether the genetic alphabet expansion system actually increases nucleic acid functionalities. We recently applied our unnatural base pair system to in vitro selection (SELEX), using a DNA library containing four natural bases and an unnatural base, and succeeded in the generation of high-affinity DNA aptamers that specifically bind to target proteins. Only a few hydrophobic unnatural bases greatly augmented the affinity of the aptamers. Here, we describe a new approach (genetic alphabet Expansion SELEX, ExSELEX), using our hydrophobic unnatural base pair system for high affinity DNA aptamer generation. PMID- 26552816 TI - Capillary Electrophoresis for the Selection of DNA Aptamers Recognizing Activated Protein C. AB - Capillary electrophoresis-based SELEX (CE-SELEX) is an efficient technique for the isolation of aptamers binding to a wide range of target molecules. CE-SELEX has a number of advantages over conventional SELEX procedures such as the selection of aptamers can be performed on non-immobilized targets, usually within a fewer number of selection cycles. Here we describe a complete procedure of CE SELEX using activated protein C (APC) as the target protein. PMID- 26552817 TI - Preparation of SELEX Samples for Next-Generation Sequencing. AB - Fuelled by massive whole genome sequencing projects such as the human genome project, enormous technological advancements and therefore tremendous price drops could be achieved, rendering next-generation sequencing very attractive for deep sequencing of SELEX libraries. Herein we describe the preparation of SELEX samples for Illumina sequencing, based on the already established whole genome sequencing workflow. We describe the addition of barcode sequences for multiplexing and the adapter ligation, avoiding associated pitfalls. PMID- 26552818 TI - Next-Generation Analysis of Deep Sequencing Data: Bringing Light into the Black Box of SELEX Experiments. AB - In silico analysis of next-generation sequencing data (NGS; also termed deep sequencing) derived from in vitro selection experiments enables the analysis of the SELEX procedure (Systematic Evolution of Ligands by EXponential enrichment) in an unprecedented depth and improves the identification of aptamers. Besides quality control and optimization of starting libraries, advanced screening strategies for difficult targets or early identification of rare but high quality aptamers which are otherwise lost in the in vitro selection experiments become possible. The high information content of sequence data obtained from selection experiments is furthermore useful for subsequent lead optimization. PMID- 26552819 TI - Aptamer Binding Studies Using MicroScale Thermophoresis. AB - The characterization and development of highly specific aptamers requires the analysis of the interaction strength between aptamer and target. MicroScale Thermophoresis (MST) is a rapid and precise method to quantify biomolecular interactions in solution at microliter scale. The basis of this technology is a physical effect referred to as thermophoresis, which describes the directed movement of molecules through temperature gradients. The thermophoretic properties of a molecule depend on its size, charge, and hydration shell. Since at least one of these parameters is altered upon binding of a ligand, this method can be used to analyze virtually any biomolecular interaction in any buffer or complex bioliquid. This section provides a detailed protocol describing how MST is used to obtain quantitative binding parameters for aptamer-target interactions. The two DNA-aptamers HD1 and HD22, which are targeted against human thrombin, are used as model systems to demonstrate a rapid and straightforward screening approach to determine optimal buffer conditions. PMID- 26552820 TI - Label-Free Determination of the Dissociation Constant of Small Molecule-Aptamer Interaction by Isothermal Titration Calorimetry. AB - Isothermal titration calorimetry (ITC) is a powerful label-free technique to determine the binding constant as well as thermodynamic parameters of a binding reaction and is therefore well suited for the analysis of small molecule-RNA aptamer interaction. We will introduce you to the method and present a protocol for sample preparation and the calorimetric measurement. A detailed note section will point out useful tips and pitfalls. PMID- 26552821 TI - Applications of Aptamers in Flow and Imaging Cytometry. AB - Aptamers compete with antibodies in many applications, in which high-affinity and specificity ligands are needed. In this regard, fluorescence-tagged aptamers have gained applications in flow and imaging cytometry for detecting cells expressing distinct antigens. Here we present prospective methods, as a starting point, for using these high-affinity ligands for cytometry applications. PMID- 26552822 TI - In Vitro and In Vivo Imaging of Fluorescent Aptamers. AB - Fluorescence imaging techniques could be used in different ways to study the interaction of aptamers with biological systems from cell culture to animal models. Here, we present the methods developed in our laboratory for fluorescently labeled aptamers, study their internalization inside living cells using time-lapse microscopy, and monitor their biodistribution in mice bearing subcutaneous xenograft tumors using planar fluorescence imaging and fluorescence diffuse optical tomography (fDOT). PMID- 26552823 TI - Crystallographic Pursuit of a Protein-RNA Aptamer Complex. AB - Only a few of the aptamers designed to selectively target proteins have been structurally characterized, such as those that target thrombin, von Willebrand factor, Plasmodium falciparum lactate dehydrogenase, interleukin 6, and platelet derived growth factor B. Most of these aptamers are composed of DNA and were designed as therapeutics/diagnostics for targets found in human plasma. Recently, the crystal structure of a complex between an RNA aptamer and an intracellular target, G protein-coupled receptor kinase 2, was determined. Herein is described the overall approach used to isolate crystals that would allow the identification of the key interactions between aptamer and kinase. These strategies may be useful in structural characterization of other SELEX-generated RNA aptamer complexes. PMID- 26552824 TI - Voltammetric Aptasensor Based on Magnetic Beads Assay for Detection of Human Activated Protein C. AB - Aptamers are defined as new generation of nucleic acids, which has recently presented promising specifications over to antibodies. An increasing number of electrochemical studies related to aptamer-based sensors, so-called aptasensors have been introduced in the literature. Herein, the interaction between human activated protein C (APC) and its cognate DNA aptamer (DNA APT) was performed at the surface of magnetic beads (MBs), followed by voltammetric detection using disposable graphite electrodes (PGEs). PMID- 26552825 TI - Apta-PCR. AB - Real-time Apta-PCR is a methodology that can be used for a wide variety of applications ranging from food quality control to clinical diagnostics. This method takes advantage of the combination of the sensitivity of nucleic acid amplification with the selectivity of aptamers. Ultra-low detection of target analyte can potentially be achieved, or, improved detection limits can be achieved with aptamers of low-medium affinity. Herein, we describe a generic methodology coined real-time Apta-PCR, using a model target (beta-conglutin) and a competitive format, which can be adapted for the detection of any target which an aptamer has been selected for. PMID- 26552826 TI - Aptamer-Based Enzyme Capture Assay for Measurement of Plasma Thrombin Levels. AB - The quantification of circulating thrombin is a valuable tool to accurately assess the activity of the blood coagulation system. Here, we describe the combined application of the thrombin-specific reversible active-site inhibitor argatroban and the DNA-aptamer HD1-22 for conduction of an enzyme capture assay for reliable measurement of plasma thrombin levels. PMID- 26552827 TI - Application of Aptamers in Histopathology. AB - Aptamers are proving to be exceedingly effective in a number of applications. Given the disadvantages of antibodies, such as batch-to-batch variation and cross reactivity, aptamers have the potential to revolutionize the field of histopathology due to their high specificity and the ease of their synthesis and modification. Here, we describe a chromogenic staining method for paraffin embedded tissue sections with FITC-labeled aptamers. PMID- 26552828 TI - Aptamer Stainings for Super-resolution Microscopy. AB - Fluorescence microscopy is an invaluable tool to visualize molecules in their biological context with ease and flexibility. However, studies using conventional light microscopy have been limited to the resolution that light diffraction allows (i.e., ~200 nm). This limitation has been recently circumvented by several types of advanced fluorescence microscopy techniques, which have achieved resolutions of up to ~10 nm. The resulting enhanced imaging precision has helped to find important cellular details that were not visible using diffraction limited instruments. However, it has also revealed that conventional stainings using large affinity tags, such as antibodies, are not accurate enough for these imaging techniques. Since aptamers are substantially smaller than antibodies, they could provide a real advantage in super-resolution imaging. Here we compare the live staining of transferrin receptors (TfnR) obtained with different fluorescently labeled affinity probes: aptamers, specific monoclonal antibodies, or the natural receptor ligand transferrin. We observed negligible differences between these staining strategies when imaging is performed with conventional light microscopy (i.e., laser scanning confocal microscopy). However, a clear superiority of the aptamer tag over antibodies became apparent in super-resolved images obtained with stimulated emission depletion (STED) microscopy. PMID- 26552829 TI - Synthesis and Characterization of Aptamer-Targeted SNALPs for the Delivery of siRNA. AB - Aptamers selected against cell surface receptors represent a unique set of ligands that can be used to target nanoparticles and other therapeutics to specific cell types. Here, we describe a method for using aptamers to deliver stable nucleic acid lipid particles (SNALPs) encapsulating small interfering RNA (siRNA) to cells in vitro. Using this method, we have demonstrated the ability of aptamer-conjugated SNALPs to achieve target-specific delivery and siRNA-mediated knockdown of a gene of interest. We also describe methods to characterize SNALP size, siRNA encapsulation efficiency, and aptamer conjugation efficiency. PMID- 26552830 TI - Screening of Genetic Switches Based on the Twister Ribozyme Motif. AB - The recent description of a new class of small endonucleolytic ribozymes termed twister opened new avenues into the development of artificial riboswitches, providing new tools for the development of artificial genetic circuits in bacteria. Here we present a method to develop new ligand-dependent riboswitches, employing the newly described catalytic motif as an expression platform in conjugation with naturally occurring or in vitro-selected aptameric domains. The twister motif is an outstandingly flexible tool for the development of highly active ribozyme-based riboswitches able to control gene expression in a ligand dependent manner in Escherichia coli. PMID- 26552831 TI - Manual-based cognitive behavioral and cognitive rehabilitation therapy for young onset dementia: a case report. AB - There is a growing attention worldwide to young-onset dementia (YOD) and this group's special challenges and needs. The literature on psychosocial interventions for this population is scarce, and little is known about the specific challenges and benefits of working therapeutically with this group of patients. The aim of this study was to explore if a manual-based structured cognitive behavioral/cognitive rehabilitation program would be beneficial for these patients. One case, a 63-year-old woman with YOD, is presented to illustrate how this intervention can be applied to individual patients to manage depressive symptoms in YOD. PMID- 26552833 TI - Integron diversity in bacterial communities of freshwater sediments at different contamination levels. AB - Integrons, genetic elements known to be involved in the adaptation of pathogenic bacteria, were first discovered in the clinical setting. However, they are ancient structures found in various environments. When clinical integrons have a low diversity, with three integrases and gene cassettes essentially encoding antibiotic resistance, in natural environments, integrons show a greater diversity, of both gene cassettes and integrases. Although a large number of gene cassettes from environmental samples have been identified, integrase diversity remains poorly documented, and has not yet been investigated in freshwater environments. The work presented here explores environmental integrons in sediments from a freshwater environment, with emphasis on integrases. Integron diversity in bacterial communities was analyzed at sampling stations with different contamination levels and contaminant types. A total of 684 integrase sequences were obtained and grouped into 322 previously undescribed integron classes, revealing a diversity wider than that previously expected in non clinical environments. The bacterial community structures did not fully explain the integron diversity suggesting that integrase diversity could be influenced by contamination level, and that contaminant type could influence gene cassette diversity. These results provide further arguments for the involvement of integrons in the adaptation of bacterial communities in response to contaminants in natural environments. PMID- 26552834 TI - Sequential Patterns of Health Conditions and Financial Outcomes in Late Life: Evidence From the Health and Retirement Study. AB - The cost and prevalence of chronic health conditions increase in late life and can negatively impact accumulated wealth. Based on the financial challenges midaged and older adults face, we sought to understand the evolution of distinctive sequences of chronic health conditions and how these sequences affect retirement savings. We used 10 waves of the Health and Retirement Study and tracked the health states and changes in wealth of 5,540 individuals. We identified five typical sequences of chronic health conditions, which are defined as follows: Multimorbidity, Comorbidity, Mild Disease, Late Event, and No Disease. Wealth accumulation differed across the five sequences. Multimorbidity and Comorbidity were the most costly sequences. Individuals with these health patterns, respectively, had $91,205 and $95,140, less net worth than respondents identified with No Disease. Our findings suggest policy makers consider sequential disease patterns when planning for the health-care needs and expenditures of older Americans. PMID- 26552835 TI - Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials. AB - As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (-89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (-81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner. PMID- 26552837 TI - New blood marker can detect chronic kidney disease, study shows. PMID- 26552836 TI - Co-morbid personality disorder in early intervention psychosis clients is associated with greater key worker emotional involvement. AB - AIM: Co-morbid personality disorder (PD) is associated with poorer outcomes in psychosis patients, but it is not known whether these patterns are present at illness onset. This study investigated the prevalence of co-morbid PD in clients of an Early Intervention in Psychosis Service (EIPS) and compared key worker engagement and service use between patients with and without co-morbid PD. METHOD: Forty-nine participants were recruited from an inner London NHS EIPS. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Axis II Disorders was administered to identify whether participants met criteria for a diagnosis of PD. Key workers completed measures investigating the therapeutic relationship and emotional involvement. Data on service use over a 2-year period from the date on which the patient was accepted by the EIPS were collected from electronic clinical records. Service use and key worker informed data were collected blind to PD diagnosis. RESULTS: Twenty-two of the 49 (45%) patients met criteria for co-morbid PD. Keyworker worry and tension were significantly higher in relation to patients with co-morbid PD compared with those without. There were no significant differences between groups in appointments offered or attended, but patients with co-morbid PD were significantly less likely to be admitted to hospital than those without. CONCLUSIONS: Co-morbid PD is common in EIPS patients. The EIPS model is both assertive and intensive; although this appears to be effective in preventing hospital admissions, this does not equip professionals to manage the higher emotional burden associated with a co-morbid PD diagnosis. PMID- 26552838 TI - High-throughput automated dissolution method applicable for a wide dose range of controlled release pellets. AB - The aim of the present study was to demonstrate the application of an automated high-throughput (HT) dissolution method as a useful screening tool for characterization of controlled release pellets in the formulation development phase. Five controlled release pellet formulations with drug substances exhibiting high or low solubility were chosen to investigate the correlation of the automated HT dissolution method with the conventional dissolution testing. Overall, excellent correlations (R(2 )>( )0.96) between the HT and the conventional dissolution method were obtained. In one case the initial unsatisfactory correlation (R(2 )=( )0.84) and poor method agreement (SD = 12.5) was improved by optimizing the HT dissolution method with design of experiment approach. Here in comparison to initial experimental HT dissolution settings, increased amount of pellets (25% of the capsule filling mass), lower temperature (22 degrees C) and no shaking resulted in significantly better correlation (R(2 )=( )0.97) and method agreement (SD = 5.3). These results show that such optimization is valuable for the development of HT dissolution methods. In conclusion, the high correlation of dissolution profiles obtained from the conventional and the automated HT dissolution method combined with low within sample and measurement system variability, justifies the utilization of the automated HT dissolution method during development phase of controlled release pellets. PMID- 26552839 TI - Interface-designed Membranes with Shape-controlled Patterns for High-performance Polymer Electrolyte Membrane Fuel Cells. AB - Polymer electrolyte membrane fuel cell is a promising zero-emission power generator for stationary/automotive applications. However, key issues, such as performance and costs, are still remained for an economical commercialization. Here, we fabricated a high-performance membrane electrode assembly (MEA) using an interfacial design based on well-arrayed micro-patterned membranes including circles, squares and hexagons with different sizes, which are produced by a facile elastomeric mold method. The best MEA performance is achieved using patterned Nafion membrane with a circle 2 MUm in size, which exhibited a very high power density of 1906 mW/cm(2) at 75 degrees C and Pt loading of 0.4 mg/cm(2) with 73% improvement compared to the commercial membrane. The improved performance are attributed to the decreased MEA resistances and increased surface area for higher Pt utilization of over 80%. From these enhanced properties, it is possible to operate at lower Pt loading of 0.2 mg/cm(2) with an outstanding performance of 1555 mW/cm(2) and even at air/low humidity operations. PMID- 26552841 TI - Pancreatic cancer surgery in elderly patients: Balancing between short-term harm and long-term benefit. A population-based study in the Netherlands. AB - BACKGROUND: At a national level, it is unknown to what degree elderly patients with pancreatic or periampullary carcinoma benefit from surgical treatment compared to their younger counterparts. We investigated resection rates and outcomes after surgical treatment among elderly patients. METHODS: From the Netherlands Cancer Registry, 20 005 patients diagnosed with primary pancreatic or periampullary cancer in 2005-2013 were selected. The associations between age (<70, 70-74, 75-79, >=80 years) and resection rates were investigated using chi(2) tests, and surgical outcomes (30-, 90-day mortality) were evaluated using logistic regression analysis. Overall survival after resection was investigated by means of Kaplan-Meier and Cox proportional hazard regression analysis. RESULTS: During the study period, resection rates increased in all age groups (<70 years: 20-30%, p < 0.001; >=80 years: 2-8%, p < 0.001). Of 3845 patients who underwent tumour resection for pancreatic or periampullary carcinoma, the proportion of octogenarians increased from 3.5% to 5.5% (p = 0.03), whereas postoperative mortality did not increase (30-day: 6-3%, p = 0.06; 90-day: 9-8%, p = 0.21). With rising age, 30-day postoperative mortality increased (4-5-7-8%, respectively, p < 0.001), while 90-day mortality was 6-10-13-12% (p < 0.001) and three-year overall survival rates after surgery were 35-33-28-31%, respectively (p < 0.001). After adjustment for confounding factors, octogenarians who survived 90 days postoperative exhibited an overall survival close to younger patients [hazard ratio (>=80 vs. <70 years) = 1.21, 95% confidence interval (0.99-1.47), p = 0.07]. CONCLUSION: Despite higher short-term mortality, octogenarians who underwent pancreatic resection showed long-term survival similar to younger patients. With careful patient screening and counselling of elderly patients, a further increase of resection rates may be combined with improved outcomes. PMID- 26552842 TI - Role of pharmacist in cardiovascular disease-related health promotion and in hypertension and dyslipidemia management: a cross-sectional study in the State of Qatar. AB - RATIONALE, AIMS AND OBJECTIVES: In Qatar, cardiovascular diseases (CVD) have recently become the leading cause of morbidity and mortality. Prevention, detection and management of CVD risk factors reduce CVD chance. The study objectives were to assess Qatar pharmacists' involvement in CVD health promotion, to identify the activities that they currently provide to patients with CVD risk factors, to describe their attitudes towards their involvement in CVD prevention and to assess their perceived barriers for provision of CVD prevention services METHOD: We conducted a cross-sectional survey of community and ambulatory pharmacists in Qatar. Pharmacist characteristics, involvement in CVD-related activities along with their attitudes and perceived barriers were analysed using frequency distributions. Bivariate linear regression models were used to test for associations between CVD health promotion activity score and each variable. Variables with a P-value of 0.20 or less were included in the multivariate model. RESULTS: A total of 141 pharmacists completed the survey (response rate 60%). More than 70% responded with rarely or never to 6 out of the 10 CVD health promotion activities. Eighty-four per cent and 68% always or often describe to patients the appropriate time to take antihypertensive medications and the common medication adverse effects, respectively. Yet, 50% rarely or never review the medication refill history or provide adherence interventions. Lack of CVD educational materials was the top perceived barrier (55%) in addition to lack of having private counselling area (44.6%), and lack of time (38.3%). Females and community pharmacists were more involved in CVD health promotion (P = 0.046 and P = 0.017, respectively) than their counterparts. Health promotion practice increased with increasing attitudes score and decreased with increased barriers score (P = 0.012 and P = 0.001). CONCLUSION: The scope of pharmacy practice in CVD prevention is limited in Qatar. Efforts need to be exerted to increase pharmacists' involvement in CVD prevention. PMID- 26552840 TI - Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. AB - Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-beta-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression. PMID- 26552843 TI - Extremely High Thermal Conductivity of Aligned Carbon Nanotube-Polyethylene Composites. AB - The ultra-low thermal conductivity of bulk polymers may be enhanced by combining them with high thermal conductivity materials such as carbon nanotubes. Different from random doping, we find that the aligned carbon nanotube-polyethylene composites has a high thermal conductivity by non-equilibrium molecular dynamics simulations. The analyses indicate that the aligned composite not only take advantage of the high thermal conduction of carbon nanotubes, but enhance thermal conduction of polyethylene chains. PMID- 26552844 TI - Leukemia cutis in myelodysplastic syndrome and chronic myelomonocytic leukemia patients treated with adjusted dose 5-azacitidine. PMID- 26552845 TI - Synthesis of Hierarchical Nanoporous Microstructures via the Kirkendall Effect in Chemical Reduction Process. AB - A series of novel hierarchical nanoporous microstructures have been synthesized through one-step chemical reduction of micron size Cu2O and Co3O4 particles. By controlling the reduction time, non-porous Cu2O microcubes sequentially transform to nanoporous Cu/Cu2O/Cu dented cubic composites and hollow eightling-like Cu microparticles. The mechanism involved in the complex structural evolution is explained based on oxygen diffusion and Kirkendall effect. The nanoporous Cu/Cu2O/Cu dented cubic composites exhibit superior electrochemical performance as compared to solid Cu2O microcubes. The reduction of nonporous Co3O4 also exhibits a uniform sequential reduction process from nonporous Co3O4 to porous Co3O4/CoO composites, porous CoO, porous CoO/Co composites, and porous foam-like Co particles. Nanoscale channels originate from the particle surface and eventually develop inside the entire product, resulting in porous foam-like Co microparticles. The Kirkendall effect is believed to facilitate the formation of porous structures in both processes. PMID- 26552846 TI - Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration Via Distinct and Overlapping Mechanisms. AB - Osteoblast differentiation and migration are necessary for bone formation during bone remodeling. Mice lacking the proline-rich tyrosine kinase Pyk2 (Pyk2-KO) have increased bone mass, in part due to increased osteoblast proliferation. Megakaryocytes (MKs), the platelet-producing cells, also promote osteoblast proliferation in vitro and bone-formation in vivo via a pathway that involves Pyk2. In the current study, we examined the mechanism of action of Pyk2, and the role of MKs, on osteoblast differentiation and migration. We found that Pyk2-KO osteoblasts express elevated alkaline phosphatase (ALP), type I collagen and osteocalcin mRNA levels as well as increased ALP activity, and mineralization, confirming that Pyk2 negatively regulates osteoblast function. Since Pyk2 Y402 phosphorylation is important for its catalytic activity and for its protein scaffolding functions, we expressed the phosphorylation-mutant (Pyk2(Y402F) ) and kinase-mutant (Pyk2(K457A) ) in Pyk2-KO osteoblasts. Both Pyk2(Y402F) and Pyk2(K457A) reduced ALP activity, whereas only kinase-inactive Pyk2(K457A) inhibited Pyk2-KO osteoblast migration. Consistent with a role for Pyk2 on ALP activity, co-culture of MKs with osteoblasts led to a decrease in the level of phosphorylated Pyk2 (pY402) as well as a decrease in ALP activity. Although, Pyk2 KO osteoblasts exhibited increased migration compared to wild-type osteoblasts, Pyk2 expression was not required necessary for the ability of MKs to stimulate osteoblast migration. Together, these data suggest that osteoblast differentiation and migration are inversely regulated by MKs via distinct Pyk2 dependent and independent signaling pathways. Novel drugs that distinguish between the kinase-dependent or protein-scaffolding functions of Pyk2 may provide therapeutic specificity for the control of bone-related diseases. PMID- 26552847 TI - Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers. AB - Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (DeltaBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions. PMID- 26552848 TI - Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. AB - Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy. PMID- 26552849 TI - Redox-Responsive Polyphosphoester-Based Micellar Nanomedicines for Overriding Chemoresistance in Breast Cancer Cells. AB - Multidrug resistance (MDR) has been recognized as a key factor contributing to the failure of chemotherapy for cancer in the clinic, often due to insufficient delivery of anticancer drugs to target cells. For addressing this issue, a redox responsive polyphosphoester-based micellar nanomedicine, which can be triggered to release transported drugs in tumor cells, has been developed. The micelles are composed of diblock copolymers with a hydrophilic PEG block and a hydrophobic polyphosphoester (PPE) block bearing a disulfide bond in a side group. After incubating the redox-responsive micelles with drug-resistant tumor cells, the intracellular accumulation and retention of DOX were significantly enhanced. Moreover, after internalization by MDR cancer cells, the disulfide bond in the side group was cleaved by the high intracellular glutathione levels, resulting in a hydrophobic to hydrophilic transition of the PPE block and subsequent disassembly of the micelles. Thus, the encapsulated DOX was rapidly released, and abrogation of drug resistance in the cancer cells was observed in vitro. Moreover, the DOX-loaded redox-responsive micelles exhibited significantly enhanced inhibition of tumor growth in nude mice bearing MCF-7/ADR xenograft tumors via tail vein injection, indicating that such micelles have great potential in overcoming MDR for cancer therapy. PMID- 26552851 TI - Polyradiculopathy and Gastroparesis due to Cytomegalovirus Infection in AIDS: A Case Report and Review of Literature. AB - BACKGROUND: Cytomegalovirus (CMV) infection has been well described as an opportunistic infection of patients with human immunodeficiency virus (HIV). To the best of our knowledge, this is the first case report of a patient with AIDS and lumbosacral polyradiculopathy, associated with gastroparesis resulting from CMV infection. CASE REPORT: A 46-year-old Hispanic woman with a history of HIV for 10 years was admitted to our hospital for nausea, vomiting, urinary retention, and generalized weakness. Bilateral lower extremity examination revealed flaccid paraplegia, decreased sensations from the groin downwards, bilateral lower extremity areflexia, and absent plantar reflexes, with enlarged urinary bladder. CMV was detected in CSF by PCR, and cervical and lumbar magnetic resonance imaging (MRI) revealed intense nodular leptomeningeal enhancement from the lower thoracic cord and extending along the conus medullaris/filum terminalis and nerve roots. Gastric emptying scintigraphy revealed severe delayed gastric emptying time. Ganciclovir was initiated and her neurological symptoms and gastrological symptoms gradually improved. Over 8 weeks, nausea and vomiting resolved and the patient was able to walk before being discharged from the hospital. CONCLUSIONS: Polyradiculopathy and gastroparesis can result from CMV infection in AIDS patients. Whether the mechanism is secondary to viral infection or immune systems remains unclear. It is important for physicians to be aware of this uncommon presentation in the antiretroviral therapy (ART) era. CMV treatment should be initiated immediately once diagnosis is confirmed. PMID- 26552850 TI - A targeted proteomic strategy for the measurement of oral cancer candidate biomarkers in human saliva. AB - Head and neck cancers, including oral squamous cell carcinoma (OSCC), are the sixth most common malignancy in the world and are characterized by poor prognosis and a low survival rate. Saliva is oral fluid with intimate contact with OSCC. Besides non-invasive, simple, and rapid to collect, saliva is a potential source of biomarkers. In this study, we build an SRM assay that targets fourteen OSCC candidate biomarker proteins, which were evaluated in a set of clinically-derived saliva samples. Using Skyline software package, we demonstrated a statistically significant higher abundance of the C1R, LCN2, SLPI, FAM49B, TAGLN2, CFB, C3, C4B, LRG1, SERPINA1 candidate biomarkers in the saliva of OSCC patients. Furthermore, our study also demonstrated that CFB, C3, C4B, SERPINA1 and LRG1 are associated with the risk of developing OSCC. Overall, this study successfully used targeted proteomics to measure in saliva a panel of biomarker candidates for OSCC. PMID- 26552854 TI - Social housing provision for minority ethnic older people with dementia: Findings from a qualitative study. AB - Little research has explored how not-for-profit housing providers, often termed Housing Associations in the United Kingdom, meet the needs of older tenants with dementia who are from black and ethnic minority communities. This article presents findings from an exploratory study conducted in 2015. The study took an audit approach, investigating current practice and policy in 12 Housing Associations. All were developing their understanding of dementia; some were augmenting their standard rented property portfolio to include housing with care provision; and most had policies relating to equalities and diversity and were offering dementia training to members of staff. None appeared to have fully integrated the three strands of housing services, dementia care, and cultural or ethnicity-related needs and preferences. A range of strategies was reported as being developed to meet tenants' changing circumstances. Anxiety about the cost of adaptations was commonly reported, although the nature and extent of this were ill-defined. Discussion focuses on the findings' implications for housing providers and for dementia professionals. PMID- 26552852 TI - Reducing suicidal ideation in home health care: results from the CAREPATH depression care management trial. AB - OBJECTIVES: The study evaluated the effectiveness of a depression care management intervention in reducing suicidal ideation (SI) among home health patients. METHODS: Data come from the cluster-randomized effectiveness trial of the Depression Care for Patients at Home (Depression CAREPATH), an intervention that integrates depression care management into the routine nursing visits of Medicare home health patients screening positive for depression. Patients were interviewed at baseline, 3, 6, and 12-month follow-up. SI was measured using the Hamilton Rating Scale for Depression item. We compared likelihood of any level of SI between intervention and usual care patients using longitudinal logistic mixed effects models. RESULTS: A total of 306 eligible patients enrolled in the trial. Among them, 70 patients (22.9%) reported SI at baseline. Among patients with SI, patients under the care of nurses randomized to CAREPATH were less likely to report SI over the study period (odds ratio = 0.51, 95% CI; 0.24-1.07), with 63.6% of usual care versus 31.3% of CAREPATH participants continuing to report SI after one year. Baseline major depression, greater perceived burdensomeness, and greater functional disability were associated with greater likelihood of SI. CONCLUSION: SI is reported in more than 10% of Medicare home health patients. The Depression CAREPATH intervention was associated with a reduction in patients reporting SI at one year, compared to enhanced usual care. Given relative low burden on nursing staff, depression care management may be an important component of routine home health practices producing long-term reduction in SI among high risk patients. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26552856 TI - Dementia case management through the eyes of informal carers: A national evaluation study. AB - This paper focuses on the evaluation of dementia case management in the Netherlands, as well as factors associated with positive evaluations of informal caregivers. A survey was completed by 554 informal carers. The majority of the informal carers were older (69% was 55+), and female (73%), and often concerned the partner or adult children of the person with dementia. Eighty percent indicated that the contact with the case manager facilitated their role as informal carer, while 95% or more stated that the case manager showed sufficient understanding, allowed enough space to decide together on how to approach problems in the care, took time to listen to their story, gave sufficient attention to and showed interest in their relative, took their schedule into account and/or kept appointments. Contrary to the expectations, multilevel analyses did not show association between informal caregivers' care burden and the evaluation of case management. Neither were the period living with dementia and the number of personal contacts with the case manager associated with the evaluations of informal caregivers. However, being the partner of the patient was significantly related ( p < 0.05) to a positive overall evaluation by informal carers. These results suggest that sufficient case management resources should be offered and targeted especially towards partners of people with dementia. PMID- 26552857 TI - No substitute for real data: A cautionary note on the use of phylogenies from birth-death polytomy resolvers for downstream comparative analyses. AB - The statistical estimation of phylogenies is always associated with uncertainty, and accommodating this uncertainty is an important component of modern phylogenetic comparative analysis. The birth-death polytomy resolver is a method of accounting for phylogenetic uncertainty that places missing (unsampled) taxa onto phylogenetic trees, using taxonomic information alone. Recent studies of birds and mammals have used this approach to generate pseudoposterior distributions of phylogenetic trees that are complete at the species level, even in the absence of genetic data for many species. Many researchers have used these distributions of phylogenies for downstream evolutionary analyses that involve inferences on phenotypic evolution, geography, and community assembly. I demonstrate that the use of phylogenies constructed in this fashion is inappropriate for many questions involving traits. Because species are placed on trees at random with respect to trait values, the birth-death polytomy resolver breaks down natural patterns of trait phylogenetic structure. Inferences based on these trees are predictably and often drastically biased in a direction that depends on the underlying (true) pattern of phylogenetic structure in traits. I illustrate the severity of the phenomenon for both continuous and discrete traits using examples from a global bird phylogeny. PMID- 26552858 TI - Phytoextraction of heavy metals by Sesuvium portulacastrum l. a salt marsh halophyte from tannery effluent. AB - The present study investigated the sources for remediation of heavy metals and salts from tannery effluent using salt marsh halophyte Sesuvium portulacastrum. From the results observed, in tannery effluent treated soil from 1 kg dry weight of plant sample, Sesuvium portulacastrum accumulated 49.82 mg Cr, 22.10 mg Cd, 35.10 mg Cu and 70.10 mg Zn and from 1 g dry weight of the plant sample, 246.21 mg Na Cl. Cultivation of Sesuvium portulacastrum significantly reduced the EC, pH and SAR levels in tannery effluent and salt treated soil and correspondingly increased in plant sample after 125 days of cultivation. In conclusion, Sesuvium portulacastrum was an efficient in accumulating heavy metals such as Chromium, Cadmium, Copper and Zinc, sodium and chloride maximum through its leaves when compared to stem and root. The finding of these bioacccumulation studies indicates that Sesuvium portulacastrum could be used for phytoremediation of tannery effluent contaminated field. PMID- 26552859 TI - Dual-emissive Polymer Dots for Rapid Detection of Fluoride in Pure Water and Biological Systems with Improved Reliability and Accuracy. AB - It is of paramount importance to develop new probes that can selectively, sensitively, accurately and rapidly detect fluoride in aqueous media and biological systems, because F(-) is found to be closely related to many health and environmental concerns. Herein, a dual-emissive conjugated polyelectrolyte P1 containing phosphorescent iridium(III) complex was designed and synthesized, which can form ultrasmall polymer dots (Pdots) in aqueous media. The F(-) responsive tert-butyldiphenylsilyl moiety was introduced into iridium(III) complex as the signaling unit for sensing F(-) with the quenched phosphorescence. Thus, the dual-emissive Pdots can rapidly and accurately detect F(-) in aqueous media and live cells as a ratiometric probe by measuring the change in the ratio of the F(-)-sensitive red phosphorescence from iridium(III) complex to the F(-) insensitive blue fluorescence from polyfluorene. Moreover, the interaction of Pdots with F(-) also changes its emission lifetime, and the lifetime-based detection of F(-) in live cells has been realized through photoluminescence lifetime imaging microscopy for the first time. Both the ratiometric luminescence and lifetime imaging have been demonstrated to be resistant to external influences, such as the probe's concentration and excitation power. This study provides a new perspective for the design of promising Pdots-based probes for biological applications. PMID- 26552860 TI - Fabrication of Fe-Doped LiCoO2 Sandwich-Like Nanocomposites as Excellent Performance Cathode Materials for Lithium-Ion Batteries. AB - In this article, the two-layer sandwiched graphene@LiFe0.Co0.8O2 nanoparticles (SG@LFCO) have been prepared and investigated as high-rate and long-life cathode materials for rechargeable lithium-ion batteries. The materials possess a high surface area (267.1 m(2) g(-1)) and lots of void spaces. By combining various favorable conditions, such as Fe doping, coating graphene, and designing novel morphology, the as-prepared materials deliver a specific capacity of 115 mAh g( 1) at 10 C. At the 0.1 C cycling rate, the capacity retention of 97.2% is sustained after 250 cycles and a coulombic efficiency of around 97.6% is obtained. PMID- 26552862 TI - Sensitivity Analysis Using Risk Measures. AB - In a quantitative model with uncertain inputs, the uncertainty of the output can be summarized by a risk measure. We propose a sensitivity analysis method based on derivatives of the output risk measure, in the direction of model inputs. This produces a global sensitivity measure, explicitly linking sensitivity and uncertainty analyses. We focus on the case of distortion risk measures, defined as weighted averages of output percentiles, and prove a representation of the sensitivity measure that can be evaluated on a Monte Carlo sample, as a weighted average of gradients over the input space. When the analytical model is unknown or hard to work with, nonparametric techniques are used for gradient estimation. This process is demonstrated through the example of a nonlinear insurance loss model. Furthermore, the proposed framework is extended in order to measure sensitivity to constant model parameters, uncertain statistical parameters, and random factors driving dependence between model inputs. PMID- 26552861 TI - Antenatal corticosteroid treatment in singleton, small-for-gestational-age infants born at 24-31 weeks' gestation: a population-based study. AB - OBJECTIVE: To assess the impact of antenatal corticosteroid therapy on mortality and severe morbidities in preterm, small-for-gestational-age (SGA) neonates compared with preterm non-SGA neonates. DESIGN: Population-based study. SETTING/POPULATION: Israel National Very Low Birth Weight infant database from 1995-2012. METHODS: Singleton infants of 24-31 weeks' gestation, without major malformations. Antenatal corticosteroids were considered either any treatment or no treatment. MAIN OUTCOME MEASURES: Univariate and multivariable logistic regression analyses were performed to assess the effect of antenatal corticosteroids on neonatal mortality and a composite adverse outcome of mortality or severe neonatal morbidity. RESULTS: Among the 10 887 study infants, 1771 were SGA. Of these, 70.4% of SGA and 66.7% of non-SGA neonates were exposed to antenatal corticosteroids. Among SGA neonates, antenatal corticosteroids were associated with decreased mortality (32.2 versus 19.3%, P < 0.0001) and composite adverse outcome (54.1 versus 43.4%, P < 0.0001), similar to the effect in non-SGA neonates (mortality 26.7 versus 12.2%, P < 0.0001; composite outcome 50.5 versus 34.6%, P < 0.0001). Multivariable logistic regression analyses demonstrated a 50% reduction in mortality risk among SGA and 57% reduction in non-SGA neonates exposed to corticosteroids [OR = 0.50, 95% confidence interval (95% CI) 0.39-0.64 and OR = 0.43, 95% CI 0.38-0.47, respectively], P-value for interaction = 0.08. Composite adverse outcome risk was significantly reduced in SGA (OR = 0.67, 95% CI 0.54-0.83) and non-SGA infants (OR = 0.57, 95% CI 0.52-0.63), P-value for interaction = 0.04. CONCLUSIONS: Antenatal corticosteroids significantly reduced mortality and severe morbidities among preterm SGA neonates, with slightly a less pronounced effect compared with non-SGA preterm infants. Antenatal corticosteroids should be given to fetuses suspected of intrauterine growth retardation, at risk for preterm delivery, in order to improve perinatal outcome. TWEETABLE ABSTRACT: Antenatal steroids reduced mortality and severe morbidities among singleton, preterm SGA neonates. PMID- 26552863 TI - Sequential MR Assessment of the Susceptibility Vessel Sign and Arterial Occlusion in Acute Stroke. AB - PURPOSE: Susceptibility vessel sign (SVS) may likely influence recanalization after thrombolysis. We assessed, through the European sequential MRI database "I KNOW," the relationship between the presence of SVS on T2-weighted gradient echo imaging, its angiographic counterpart on magnetic resonance angiography and its subsequent impact on recanalization after thrombolysis. MATERIALS AND METHODS: Initial clinical and MRI characteristics and early follow up were analyzed in acute ischemic stroke patients treated with rt-Pa within 4.5 hours. Patients underwent multimodal MRI at admission. Sequential imaging performed 3 hours, 2 days and 1 month later allowed the analysis of SVS changes and recanalization. RESULTS: Fifty patients were included in the study. SVS was observed in 54% of cases at admission. SVS was still present in 46% patients at 3 hours, 16% at 2 days, and 0% at 1 month. It was an independent predictor of no recanalization after thrombolysis (P = .04). After 3 hours, SVS disappeared in only 4 cases, and was not linked with recanalization on MRA. Conversely, when SVS persisted, a partial or complete recanalization was observed in 9 and 6 cases, respectively. CONCLUSIONS: SVS is a predictor of lower recanalization rate. Its disappearance is not necessarily correlated with recanalization. PMID- 26552864 TI - Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness. AB - The A1555G mutation in the 12S rRNA gene of human mitochondrial DNA causes maternally inherited, nonsyndromic deafness, an extreme case of tissue-specific mitochondrial pathology. A transgenic mouse strain that robustly overexpresses the mitochondrial 12S ribosomal RNA methyltransferase TFB1M (Tg-mtTFB1 mice) exhibits progressive hearing loss that we proposed models aspects of A1555G related pathology in humans. Although our previous studies of Tg-mtTFB1 mice implicated apoptosis in the spiral ganglion and stria vascularis because of mitochondrial reactive oxygen species-mediated activation of AMP kinase (AMPK) and the nuclear transcription factor E2F1, detailed auditory pathology was not delineated. Herein, we show that Tg-mtTFB1 mice have reduced endocochlear potential, indicative of significant stria vascularis dysfunction, but without obvious signs of strial atrophy. We also observed decreased auditory brainstem response peak 1 amplitude and prolonged wave I latency, consistent with apoptosis of spiral ganglion neurons. Although no major loss of hair cells was observed, there was a mild impairment of voltage-dependent electromotility of outer hair cells. On the basis of these results, we propose that these events conspire to produce the progressive hearing loss phenotype in Tg-mtTFB1 mice. Finally, genetically reducing AMPK alpha1 rescues hearing loss in Tg-mtTFB1 mice, confirming that aberrant up-regulation of AMPK signaling promotes the observed auditory pathology. The relevance of these findings to human A1555G patients and the potential therapeutic value of reducing AMPK activity are discussed. PMID- 26552865 TI - ART Adherence as a Key Component of Prevention With Persons Living With HIV in Mozambique. AB - Medication adherence is an effective approach to prevent HIV transmission. In Mozambique, a country with a generalized epidemic, the government has adopted Positive Prevention (PP) training for clinicians as part of its national strategy. Our study, conducted after trainings in five clinics, examined the understanding of trained health care staff and their patients about the importance of adherence to antiretroviral therapy (ART), a key element of PP. Interviews with trained clinicians (n = 31) and patients (n = 57) were conducted and analyzed. Clinicians and patients demonstrated an understanding that ART adherence could decrease HIV transmission. However, participants also highlighted the difficulties of adherence when patients had limited access to food. At the same time that treatment as prevention awareness was increasing, poverty and widespread food insecurity were barriers to taking medications. In Mozambique, the full benefits of treatment as prevention may not be realized without adequate access to food. PMID- 26552866 TI - Multiple Roles for Nogo Receptor 1 in Visual System Plasticity. AB - During the developmental critical period for visual plasticity, discordant vision alters the responsiveness of neurons in visual cortex. The subsequent closure of the critical period not only consolidates neural function but also limits recovery of acuity from preceding abnormal visual experience. Despite species specific differences in circuitry of the visual system, these characteristics are conserved. The nogo-66 receptor 1 (ngr1) is one of only a small number of genes identified thus far that is essential to closing the critical period. Mice lacking a functional ngr1 gene retain developmental visual plasticity as adults and their visual acuity spontaneously improves after prolonged visual deprivation. Experiments employing conditional mouse genetics have revealed that ngr1 restricts plasticity within distinct circuits for ocular dominance and visual acuity. However, the mechanisms by which NgR1 limits plasticity have not been elucidated, in part because the subcellular localization and signal transduction of the protein are only partially understood. Here we explore potential mechanisms for NgR1 function in relation to manipulations that reactivate visual plasticity in adults and propose lines of investigation to address relevant gaps in knowledge. PMID- 26552867 TI - HTLV-1 drives vigorous clonal expansion of infected CD8(+) T cells in natural infection. AB - BACKGROUND: Human T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5-10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4(+) T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4(+). HTLV-1 also infects CD8(+) cells in vivo, but the relative abundance and clonal composition of the two infected subpopulations have not been studied. We used a high-throughput DNA sequencing protocol to map and quantify HTLV-1 proviral integration sites in separated populations of CD4(+) cells, CD8(+) cells and unsorted peripheral blood mononuclear cells from 12 HTLV-1 infected individuals. RESULTS: We show that the infected CD8(+) cells constitute a median of 5% of the HTLV-1 proviral load. However, HTLV-1-infected CD8(+) clones undergo much greater oligoclonal proliferation than the infected CD4(+) clones in infected individuals, regardless of disease manifestation. The CD8(+) clones are over-represented among the most abundant clones in the blood and are redetected even after several years. CONCLUSIONS: We conclude that although they make up only 5% of the proviral load, the HTLV-1-infected CD8(+) T-cells make a major impact on the clonal composition of HTLV-1-infected cells in the blood. The greater degree of oligoclonal expansion observed in the infected CD8(+) T cells, contrasts with the CD4(+) phenotype of ATL; cases of CD8(+) adult T-cell leukaemia/lymphoma are rare. This work is consistent with growing evidence that oligoclonal expansion of HTLV-1-infected cells is not sufficient for malignant transformation. PMID- 26552868 TI - Inferring intra-motif dependencies of DNA binding sites from ChIP-seq data. AB - BACKGROUND: Statistical modeling of transcription factor binding sites is one of the classical fields in bioinformatics. The position weight matrix (PWM) model, which assumes statistical independence among all nucleotides in a binding site, used to be the standard model for this task for more than three decades but its simple assumptions are increasingly put into question. Recent high-throughput sequencing methods have provided data sets of sufficient size and quality for studying the benefits of more complex models. However, learning more complex models typically entails the danger of overfitting, and while model classes that dynamically adapt the model complexity to data have been developed, effective model selection is to date only possible for fully observable data, but not, e.g., within de novo motif discovery. RESULTS: To address this issue, we propose a stochastic algorithm for performing robust model selection in a latent variable setting. This algorithm yields a solution without relying on hyperparameter tuning via massive cross-validation or other computationally expensive resampling techniques. Using this algorithm for learning inhomogeneous parsimonious Markov models, we study the degree of putative higher-order intra-motif dependencies for transcription factor binding sites inferred via de novo motif discovery from ChIP seq data. We find that intra-motif dependencies are prevalent and not limited to first-order dependencies among directly adjacent nucleotides, but that second order models appear to be the significantly better choice. CONCLUSIONS: The traditional PWM model appears to be indeed insufficient to infer realistic sequence motifs, as it is on average outperformed by more complex models that take into account intra-motif dependencies. Moreover, using such models together with an appropriate model selection procedure does not lead to a significant performance loss in comparison with the PWM model for any of the studied transcription factors. Hence, we find it worthwhile to recommend that any modern motif discovery algorithm should attempt to take into account intra-motif dependencies. PMID- 26552869 TI - Dystonia in Machado-Joseph disease: Clinical profile, therapy and anatomical basis. AB - INTRODUCTION: Dystonia is frequent in Machado-Joseph disease, but several important aspects are not yet defined, such as the detailed clinical profile, response to treatment and anatomical substrate. METHODS: We screened 75 consecutive patients and identified those with dystonia. The Burke-Marsden-Fahn Dystonia Rating Scale was employed to quantify dystonia severity. Patients with dystonia received levodopa 600 mg/day for 2 months and were videotaped before and after treatment. A blinded evaluator rated dystonia in the videos. Patients with disabling dystonia who failed to respond to levodopa treatment received botulinum toxin. Finally, volumetric T1 and diffusion tensor imaging sequences were obtained in the dystonic group using a 3T-MRI scanner to identify areas of gray and white matter that were selectively damaged. RESULTS: There were 21 patients with dystonia (28%): 9 classified as generalized and 12 as focal/segmental. Patients with dystonia had earlier onset and larger (CAG) expansions (28.9 +/- 11.7 vs 40.6 +/- 11.4; p < 0.001 and 75 vs 70; p < 0.001, respectively). Although group analyses failed to show benefit on levodopa (p = 0.07), some patients had objective improvement. In addition, ten patients received botulinum toxin resulting in a significant change in dystonia scores after 4 weeks (p = 0.03). Patients with dystonia had atrophy at pre- and paracentral cortices; whereas, non dystonic patients had occipital atrophy. Basal ganglia volume was reduced in both groups, but atrophy at the thalami, cerebellar white matter and ventral diencephali was disproportionately higher in the dystonic group. CONCLUSION: Dystonia in Machado-Joseph disease is frequent and often disabling, but may respond to levodopa. It is associated predominantly with structural abnormalities around the motor cortices and in the thalami. PMID- 26552871 TI - Isolated Cutaneous Sarcoidosis. PMID- 26552870 TI - Impact of phenolic composition on hepatoprotective and antioxidant effects of four desert medicinal plants. AB - BACKGROUND: Flavonoids and other polyphenols play a protective role in liver diseases and possess a high antioxidant capacity. OBJECTIVE: To compare and evaluate the antioxidant and hepatotoprotective activities of 4 deserts plants, Fagonia indica Burm. f., Calotropis procera R.Br., Zygophylum hamiense Schweinf. and Salsola imbricata Forssk. in correlation to their composition especially their phenolic content. METHODS: The influence of extracting solvent on total phenolic and flavonoidal contents was assessed spectrophotometrically. The flavonoid and other polyphenolic components of the methanol extracts were analyzed by RP-HPLC. DPPH radical scavenging potential of the different extracts was estimated. The hepatoprotective and antioxidant activities of the extracts against CCl4-induced hepatotoxicity in mice were evaluated. RESULTS: The flavonol quercitrin and rosmarinic acid were major in the F. indica, C. procera and S. imbricata samples, while rutin prevailed in that of Z. hamiense. The ethanolic and methanolic extracts showed noticeable DPPH radical-scavenging activity as compared to ascorbic acid. Assessment of liver enzymes revealed that oral administration of the extracts did not show any evidence of hepatotoxicity. Moreover, protection against CCl4-induced liver damage was evident upon administration of three plants extracts namely, F. indica, C. procera and S. imbricata. CONCLUSION: Overall, hepatotoxicity induced by CCl4 was effectively prevented by the three plants extracts through scavenging of free radicals and by boosting the antioxidant capacity of the liver. The protective effect of the plants could be attributed to their high quercitrin and rosmarinic acid contents. PMID- 26552872 TI - Glycyrrhizic acid, active component from Glycyrrhizae radix, prevents toxicity of graphene oxide by influencing functions of microRNAs in nematode Caenorhabditis elegans. AB - We investigated effects of pretreatment with Glycyrrhizae radix (GR) or its specific components on toxicity of graphene oxide (GO) in Caenorhabditis elegans. GR pretreatment prevented GO toxicity on function of both primary and secondary targeted organs. Among active components in GR, the beneficial effects of GR were attributable to presence of glycyrrhizic acid. Glycyrrhizic acid pretreatment suppressed translocation of GO into secondary targeted organs through intestinal barrier. Glycyrrhizic acid pretreatment recovered expression patterns of dysregulated microRNAs (miRNAs) induced by GO, and genes required for oxidative stress control acted as targeted genes for some of these miRNAs. Among these miRNAs, mir-360 mutation enhanced beneficial effects of glycyrrhizic acid. We hypothesize that glycyrrhizic acid may prevent GO toxicity and translocation by influencing functions of miRNAs which upstream regulate functions of their targeted genes. Furthermore, glycyrrhizic acid had potential to extend lifespan, and to suppress accelerated aging process induced by GO. FROM THE CLINICAL EDITOR: Exposure to graphene oxide may pose toxic effects to health, as suggested in animal studies. In this article, the authors showed that the use of glycyrrhizae radix (GR) prevented toxicity of graphene oxide in Caenorhabditis elegans. These results may provide novel strategies in the reducing potential side effects of nanoparticles. PMID- 26552873 TI - Effect of genistein added to bull semen after thawing on pronuclear and sperm quality. AB - The aim of this research was to study the effect of different genistein treatments on bull sperm after thawing on pronuclear formation after in vitro fertilization (IVF) and on different sperm quality variables. Three experiments were performed. In Experiment 1, three treatments (Control, sperm incubation for 1h at 37 degrees C with or without genistein) and two sperm concentrations during IVF (1 or 3 * 10(6)sperm/mL) were evaluated to study the influence of genistein on pronuclear formation (PNF). Sperm incubation for 1h before IVF reduced PNF regardless of sperm concentration. However, after sperm incubation and with 3 * 10(6)sperm/mL in IVF, the genistein treatment group had greater fertilization rates than the untreated group. In Experiment 2, six treatments plus the control group were performed to study the effect of genistein (presence or not) and incubation conditions (30 min at 37 degrees C, 1h at 27 degrees C or at 37 degrees C) on PNF using 3 * 10(6)sperm/mL for IVF. When incubation time was reduced to 30 min, PNF rate from the genistein treatment group was no different from either the control group or in the group in which incubation occurred for 1h at 27 degrees C. In Experiment 3, the effect of several genistein treatments (control; genistein treatment for 30 min of incubation at 37 degrees C; genistein treatment for 1h of incubation at 27 degrees C) on sperm motility, viability and DNA fragmentation were evaluated. Genistein did not improve sperm motility and, depending on the experimental group or time, it either reduced or had no effect on sperm motility. Genistein treatment did not improve sperm viability after 5h of incubation. However, genistein treatment for 1h at 27 degrees C decreased sperm DNA fragmentation compared with the control group after 5h of sperm incubation. In conclusion, the treatment of bull sperm with genistein for 1h at 27 degrees C could decrease sperm DNA fragmentation, although PNF rate after IVF and sperm motility were reduced. PMID- 26552874 TI - Antibacterial action against food-borne microorganisms and antioxidant activity of carvacrol-rich oil from Lippia origanoides Kunth. AB - BACKGROUND: Lippia origanoides Kunth from Northeast Brazil is a plant of pleasant odor used by local people as a food seasoning in substitution the oregano where its carvacrol-rich oil has showed significant antimicrobial activity against human pathogens. METHODS: GC and GC-MS analyzed the plant oil composition and its antibacterial activity was evaluated by disk diffusion and microdilution broth methods. The determination of oil antioxidant activity was made by DPPH radical scavenging assay. Oil toxicity was performed on mice. RESULTS: The main constituents of the oil were carvacrol (47.2%), thymol (12.8%), p-cymene (9.7%), and p-methoxythymol (7.4%). The oil was active against the bacteria of Bacillus cereus, B. subtilis, and Salmonella typhimurium, except for Pseudomonas aeruginosa. The antioxidant activity has displayed a high dose-response (r(2) = 0.92), with the inhibition of DPPH radical from 15 to 82%, at concentrations from 5 to 50 MUg/mL, and also by the beta-carotene bleaching assay, which showed a high inhibition of 85.2 +/- 6.8 %, corresponding to about 80% of the inhibition of Trolox (93.4 +/- 0.7%), used as a standard. The lethal dose (LD50) of the oil was determined in 1673.84 mg mL(-1). CONCLUSION: The results confirmed that the oil of L. origanoides could be utilized for the prevention of food bacterial growth, and as an antioxidative agent for retardation of food oxidation process. The oil has low toxicity, allowing its application in the food industry. Graphical Abstract Aerial parts of Lippia origanoides Kunth. PMID- 26552875 TI - Primary mucinous adenocarcinoma of the female urethra: a contemporary clinicopathologic analysis. AB - Primary mucinous adenocarcinoma of the female urethra is very rare and may lead to both diagnostic and therapeutic challenges. Although primary mucinous adenocarcinoma of the prostate and prostatic urethra has been well characterized in men, this is the largest clinicopathologic study to date of primary mucinous adenocarcinoma of the female urethra. A search was made through the files of 2 major academic institutions for cases of confirmed primary mucinous adenocarcinoma arising from the female urethra. Tumors arising from adjacent organs were excluded both clinically and pathologically in all cases. Five cases were identified. The mean patient age was 67 years (range, 54-74 years). All patients presented with a polypoid/papillary mass arising from the urethra. Pathologic stages were as follows: pT4 3 (60%) of 5 cases; pT3 1 (20%) of 5 cases, and pT2 1 (20%) of 5 cases. Immunohistochemical stains for GATA3, p63, CK7, CK20, CDX2, ER, PAX8, and beta-catenin were performed on all cases. Immunohistochemical stains were positive in the tumor cells for CDX2 in 4/5 (80%) cases; focally positive for CK20 in 4/5 (80%) cases; focally positive for CK7 in 4/5 cases (80%); and negative for p63, GATA3, ER, PAX8 and beta-catenin in all cases. In the 4 patients with available follow-up data, mean follow-up was 25 months (range, 4-54 months). It is critical for pathologists to be aware of this entity in light of potential diagnostic pitfalls and therapeutic implications. PMID- 26552876 TI - Correction. PMID- 26552877 TI - Coarctation of the aorta with left pulmonary artery stenosis: a rare association diagnosed with ECG-gated multislice dual-source CT angiography. AB - We report an extremely rare case of coarctation of the aorta with associated left pulmonary artery stenosis. This violates the traditional fetal flow pattern theory. Two-dimensional echocardiography, although being the initial imaging modality for diagnosing coarctation of the aorta, is limited in the demonstration of branch pulmonary arteries. Retrospective ECG-gated multidetector CT angiography is a non-invasive imaging technique for comprehensive assessment of the site, length and severity of the stenosed aortic segment. It is also helpful in differentiation of an interrupted aortic arch from severe coarctation. Associated pulmonary arterial and venous system anomalies can be evaluated, which dictates the management of aortic coarctation. PMID- 26552878 TI - Pneumobilia with gastric outlet obstruction. AB - Complications of peptic ulcer disease (PUD) like gastric outlet obstruction (GOO) and biliary fistula have become extremely rare with the advent of proton-pump inhibitors.This is a case of PUD presenting with GOO, a cholecystoduodenal fistula discovered incidentally on upper gastrointestinal endoscopy, and the presence of pneumobilia on a contrast-enhanced CT of the abdomen. A gastrojejunostomy with internal pyloric exclusion was performed. Since the patient did not have any signs of biliary tract disease,we decided not to operate on the fistula to prevent injury to the bile duct. The patient had an uneventful recovery. PMID- 26552879 TI - Spontaneous resolution of a recurrent axillary cystic hygroma following acute infection. AB - We report a case of spontaneous resolution of a recurrent axillary cystic hygroma in a 4-year-old boy. He presented with a 1-year history of a cystic lump in the left axilla, which intermittently changed in size. Ultrasound suggested it was a lipoma, with raised suspicions of vascular malformation. Scans were discussed in a multidisciplinary meeting and provisional diagnosis of lymphocele or slow flow lymphovascular malformation was made. It was surgically excised and histology confirmed the lesion to be a cystic hygroma. However, it recurred within 3 weeks. The patient was booked for aspiration and treatment with sclerotic agent OK 432. He developed acute infection in the cystic hygroma a week before surgical intervention and was treated with antibiotics for 5 days by his general practitioner. Acute infection led to complete spontaneous resolution of the cystic hygroma within a week. There are no other reported cases in which recurrent cystic hygroma has resolved after a week of acute infection. PMID- 26552880 TI - Soft-mask fabrication of gallium arsenide nanomembranes for integrated quantum photonics. AB - We report on the fabrication of quantum photonic integrated circuits based on suspended GaAs membranes. The fabrication process consists of a single lithographic step followed by inductively coupled-plasma dry etching through an electron-beam-resist mask and wet etching of a sacrificial layer. This method does not require depositing, etching, and stripping a hard mask, greatly reducing fabrication time and costs, while at the same time yielding devices of excellent structural quality. We discuss in detail the procedures for cleaning the resist residues caused by the plasma etching and present a statistical analysis of the etched feature size after each fabrication step. PMID- 26552881 TI - Variation in genomic methylation in natural populations of Populus simonii is associated with leaf shape and photosynthetic traits. AB - DNA methylation, one of the best-studied types of chromatin modification, suppresses the expression of transposable elements, pseudogenes, repetitive sequences, and individual genes. However, the extent and variation of genome-wide DNA methylation in natural populations of plants remain relatively unknown. To investigate variation in DNA methylation and whether this variation associates with important plant traits, including leaf shape and photosynthesis, 20 413 DNA methylation sites were examined in a poplar association population (505 individuals) using methylation-sensitive amplification polymorphism (MSAP) technology. Calculation of epi-population structure and kinships assigned individuals into subsets (K=3), revealing that the natural population of P. simonii consists of three subpopulations. Population epigenetic distance and geographic distance showed a significant correlation (r=0.4688, P<0.001), suggesting that environmental factors may affect epigenetics. Single-marker approaches were also used to identify significant marker-trait associations, which found 1087 high-confidence DNA methylation markers associated with different phenotypic traits explaining ~5-15% of the phenotypic variance. Among these loci, 147 differentially methylated fragments were obtained by sequencing, representing 130 candidate genes. Expression analysis of six candidate genes indicated that these genes might play important roles in leaf development and regulation of photosynthesis. This study provides association analysis to study the effects of DNA methylation on plant development and these data indicate that epigenetics bridges environmental and genetic factors in affecting plant growth and development. PMID- 26552882 TI - Balance between carbon gain and loss under long-term drought: impacts on foliar respiration and photosynthesis in Quercus ilex L. AB - Terrestrial carbon exchange is a key process of the global carbon cycle consisting of a delicate balance between photosynthetic carbon uptake and respiratory release. We have, however, a limited understanding how long-term decreases in precipitation induced by climate change affect the boundaries and mechanisms of photosynthesis and respiration. We examined the seasonality of photosynthetic and respiratory traits and evaluated the adaptive mechanism of the foliar carbon balance of Quercus ilex L. experiencing a long-term rainfall exclusion experiment. Day respiration (Rd) but not night respiration (Rn) was generally higher in the drought treatment leading to an increased Rd/Rn ratio. The limitation of mesophyll conductance (gm) on photosynthesis was generally stronger than stomatal limitation (gs) in the drought treatment, reflected in a lower gm/gs ratio. The peak photosynthetic activity in the drought treatment occurred in an atypical favourable summer in parallel with lower Rd/Rn and higher gm/gs ratios. The plant carbon balance was thus strongly improved through: (i) higher photosynthetic rates induced by gm; and (ii) decreased carbon losses mediated by Rd. Interestingly, photosynthetic potentials (Vc,max, Jmax, and TPU) were not affected by the drought treatment, suggesting a dampening effect on the biochemical level in the long term. In summary, the trees experiencing a 14-year long drought treatment adapted through higher plasticity in photosynthetic and respiratory traits, so that eventually the atypical favourable growth period was exploited more efficiently. PMID- 26552883 TI - The impact of abiotic factors on cellulose synthesis. AB - As sessile organisms, plants require mechanisms to sense and respond to changes in their environment, including both biotic and abiotic factors. One of the most common plant adaptations to environmental changes is differential regulation of growth, which results in growth either away from adverse conditions or towards more favorable conditions. As cell walls shape plant growth, this differential growth response must be accompanied by alterations to the plant cell wall. Here, we review the impact of four abiotic factors (osmotic conditions, ionic stress, light, and temperature) on the synthesis of cellulose, an important component of the plant cell wall. Understanding how different abiotic factors influence cellulose production and addressing key questions that remain in this field can provide crucial information to cope with the need for increased crop production under the mounting pressures of a growing world population and global climate change. PMID- 26552884 TI - A genome-wide association study of a global rice panel reveals resistance in Oryza sativa to root-knot nematodes. AB - The root-knot nematode Meloidogyne graminicola is one of the most serious nematode pests worldwide and represents a major constraint on rice production. While variation in the susceptibility of Asian rice (Oryza sativa) exists, so far no strong and reliable resistance has been reported. Quantitative trait loci for partial resistance have been reported but no underlying genes have been tagged or cloned. Here, 332 accessions of the Rice Diversity Panel 1 were assessed for gall formation, revealing large variation across all subpopulations of rice and higher susceptibility in temperate japonica accessions. Accessions Khao Pahk Maw and LD 24 appeared to be resistant, which was confirmed in large pot experiments where no galls were observed. Detailed observations on these two accessions revealed no nematodes inside the roots 2 days after inoculation and very few females after 17 days (5 in Khao Pahk Maw and <1 in LD 24, in comparison with >100 in the susceptible controls). These two cultivars appear ideal donors for breeding root knot nematode resistance. A genome-wide association study revealed 11 quantitative trait loci, two of which are close to epistatic loci detected in the Bala x Azucena population. The discussion highlights a small number of candidate genes worth exploring further, in particular many genes with lectin domains and genes on chromosome 11 with homology to the Hordeum Mla locus. PMID- 26552885 TI - The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans. AB - Experimental manipulation of protein abundance in living cells or organisms is an essential strategy for investigation of biological regulatory mechanisms. Whereas powerful techniques for protein expression have been developed in Caenorhabditis elegans, existing tools for conditional disruption of protein function are far more limited. To address this, we have adapted the auxin-inducible degradation (AID) system discovered in plants to enable conditional protein depletion in C. elegans. We report that expression of a modified Arabidopsis TIR1 F-box protein mediates robust auxin-dependent depletion of degron-tagged targets. We document the effectiveness of this system for depletion of nuclear and cytoplasmic proteins in diverse somatic and germline tissues throughout development. Target proteins were depleted in as little as 20-30 min, and their expression could be re-established upon auxin removal. We have engineered strains expressing TIR1 under the control of various promoter and 3' UTR sequences to drive tissue specific or temporally regulated expression. The degron tag can be efficiently introduced by CRISPR/Cas9-based genome editing. We have harnessed this system to explore the roles of dynamically expressed nuclear hormone receptors in molting, and to analyze meiosis-specific roles for proteins required for germ line proliferation. Together, our results demonstrate that the AID system provides a powerful new tool for spatiotemporal regulation and analysis of protein function in a metazoan model organism. PMID- 26552886 TI - Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis. AB - Angiogenesis is tightly controlled by a number of signalling pathways. Although our understanding of the molecular mechanisms involved in angiogenesis has rapidly increased, the role that biomechanical signals play in this process is understudied. We recently developed a technique to simultaneously analyse flow dynamics and vascular remodelling by time-lapse microscopy in the capillary plexus of avian embryos and used this to study the hemodynamic environment present during angiogenic sprouting. We found that sprouts always form from a vessel at lower pressure towards a vessel at higher pressure, and that sprouts form at the location of a shear stress minimum, but avoid locations where two blood streams merge even if this point is at a lower level of shear stress than the sprouting location. Using these parameters, we were able to successfully predict sprout location in quail embryos. We also found that the pressure difference between two vessels is permissive to elongation, and that sprouts will either change direction or regress if the pressure difference becomes negative. Furthermore, the sprout elongation rate is proportional to the pressure difference between the two vessels. Our results show that flow dynamics are predictive of the location of sprout formation in perfused vascular networks and that pressure differences across the interstitium can guide sprout elongation. PMID- 26552888 TI - DAF-18/PTEN locally antagonizes insulin signalling to couple germline stem cell proliferation to oocyte needs in C. elegans. AB - During development, stem cell populations rapidly proliferate to populate the expanding tissues and organs. During this phase, nutrient status, by systemically affecting insulin/IGF-1 signalling, largely dictates stem cell proliferation rates. In adults, however, differentiated stem cell progeny requirements are generally reduced and vary according to the spatiotemporal needs of each tissue. We demonstrate here that differential regulation of germline stem cell proliferation rates in Caenorhabditis elegans adults is accomplished through localized neutralization of insulin/IGF-1 signalling, requiring DAF-18/PTEN, but not DAF-16/FOXO. Indeed, the specific accumulation of oocytes, the terminally differentiated stem cell progeny, triggers a feedback signal that locally antagonizes insulin/IGF-1 signalling outputs in the germ line, regardless of their systemic levels, to block germline stem cell proliferation. Thus, during adulthood, stem cells can differentially respond within tissues to otherwise equal insulin/IGF-1 signalling inputs, according to the needs for production of their immediate terminally differentiated progeny. PMID- 26552887 TI - Neural crest cell-autonomous roles of fibronectin in cardiovascular development. AB - The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin alpha5beta1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling. PMID- 26552889 TI - In vivo quantitative imaging of photoassimilate transport dynamics and allocation in large plants using a commercial positron emission tomography (PET) scanner. AB - BACKGROUND: Although important aspects of whole-plant carbon allocation in crop plants (e.g., to grain) occur late in development when the plants are large, techniques to study carbon transport and allocation processes have not been adapted for large plants. Positron emission tomography (PET), developed for dynamic imaging in medicine, has been applied in plant studies to measure the transport and allocation patterns of carbohydrates, nutrients, and phytohormones labeled with positron-emitting radioisotopes. However, the cost of PET and its limitation to smaller plants has restricted its use in plant biology. Here we describe the adaptation and optimization of a commercial clinical PET scanner to measure transport dynamics and allocation patterns of (11)C-photoassimilates in large crops. RESULTS: Based on measurements of a phantom, we optimized instrument settings, including use of 3-D mode and attenuation correction to maximize the accuracy of measurements. To demonstrate the utility of PET, we measured (11)C photoassimilate transport and allocation in Sorghum bicolor, an important staple crop, at vegetative and reproductive stages (40 and 70 days after planting; DAP). The (11)C-photoassimilate transport speed did not change over the two developmental stages. However, within a stem, transport speeds were reduced across nodes, likely due to higher (11)C-photoassimilate unloading in the nodes. Photosynthesis in leaves and the amount of (11)C that was exported to the rest of the plant decreased as plants matured. In young plants, exported (11)C was allocated mostly (88 %) to the roots and stem, but in flowering plants (70 DAP) the majority of the exported (11)C (64 %) was allocated to the apex. CONCLUSIONS: Our results show that commercial PET scanners can be used reliably to measure whole-plant C-allocation in large plants nondestructively including, importantly, allocation to roots in soil. This capability revealed extreme changes in carbon allocation in sorghum plants, as they advanced to maturity. Further, our results suggest that nodes may be important control points for photoassimilate distribution in crops of the family Poaceae. Quantifying real-time carbon allocation and photoassimilate transport dynamics, as demonstrated here, will be important for functional genomic studies to unravel the mechanisms controlling phloem transport in large crop plants, which will provide crucial insights for improving yields. PMID- 26552891 TI - Treatment of recalcitrant granuloma annulare (GA) with adalimumab: A single center, observational study. AB - BACKGROUND: Generalized or disseminated granuloma annulare (GA) is therapeutically challenging. Adalimumab, a tumor necrosis factor-alpha antagonist, has recently been used to treat GA. OBJECTIVE: We sought to evaluate adalimumab's efficacy in treating GA. METHODS: We identified 7 patients with physician-verified GA who were treated with adalimumab. Primary endpoints were improvements in GA Investigator Global Assessment score and body surface area. Secondary end points included erythema and induration improvement. RESULTS: Seven adults, ages 51 to 77 years, were included. All patients' GA Investigator Global Assessment scores improved by 2 or greater. We found significant improvements in body surface area, erythema, and induration (average improvements by 87%, 88%, and 95%, respectively). Two patients required increases in adalimumab frequency. Two others noted GA recurrence; 1 restarted adalimumab and cleared again. Adverse events were minimal. LIMITATIONS: Conclusions are limited because of small sample size and observational nature of the study. CONCLUSION: Our results suggest that adalimumab could be an effective and well-tolerated treatment for GA. It is a particularly attractive therapy for patients who have generalized or disseminated GA. PMID- 26552892 TI - Reflections on the Nobel Prize for Medicine 2015--The Public Health Legacy and Impact of Avermectin and Artemisinin. AB - The award of the Nobel Prize to Dr Bill Campbell and Professor Satoshi Omura for their role in the discovery of avermectin and Professor Youyou Tu for her work on the development of artemisinin has been universally welcomed by the International Health community for what the Nobel Committee described as 'The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases. Campbell, Omura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable'. PMID- 26552893 TI - Geographical distribution of Dermacentor marginatus and Dermacentor reticulatus in Europe. AB - The goal of this paper is to present up-to-date maps depicting the geographical distribution of Dermacentor species in Europe based on georeferenced sampling sites. Therefore, a dataset was compiled, resulting in 1286 D. marginatus (Sulzer, 1776) and 1209 D. reticulatus (Fabricius, 1794) locations. Special emphasis is given to the region of the European Alps depicting a presumable climate barrier of the mountains and to overlaps in the distribution of both species as well as on the situation in eastern European countries. For the latter newly described Dermacentor findings comprise 59 locations in Romania and 62 locations in Ukraine. The geographical distributions of both species in Europe range from Portugal to Ukraine (and continue to the east of Kazakhstan). Although it is well known that D. marginatus is adapted to a warmer and drier climate at more southern latitudes and D. reticulatus to a moderately moist climate at more northern latitudes, the distribution limits of both species were not well known. Here, the northern and southern distribution limits for both species in Europe, as determined from the georeferenced database, were specified for D. marginatus by the belt of 33-51 degrees N latitude and for D. reticulatus by the belt of 41 57 degrees N latitude. Thus, overlapping species distributions were found between 41 degrees N and 51 degrees N. PMID- 26552894 TI - Editorial. PMID- 26552890 TI - Endometrial stem/progenitor cells: the first 10 years. AB - BACKGROUND: The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS: The published literature was searched using the PubMed database with the search terms 'endometrial stem cells and menstrual blood stem cells' until December 2014. RESULTS: Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44(+) cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146(+)PDGFRbeta(+) (platelet-derived growth factor receptor beta) and SUSD2(+) (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2(+) cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman's syndrome. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies. CONCLUSIONS: Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146(+)PDGFR-beta(+) and SUSD2(+) cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells. PMID- 26552895 TI - Development of an endoluminal intestinal attachment for a clinically applicable distraction enterogenesis device. AB - PURPOSE: Previous methods of distraction enterogenesis have relied upon blind ending intestinal segments or transmural device fixation, requiring multiple operations and potential bowel injury. We hypothesized that using a novel attachment would allow reversible device coupling to the luminal bowel surface, achieving effective endoluminal distraction. METHODS: A telescopic hydraulic device was designed with latex balloon attachments covered with high-friction mesh and a dilating fenestrated elastic mask (DFM attachment), allowing mesh-to mucosa contact only with inflation. Yorkshire pigs underwent jejunal Roux-en-Y limb creation and device placement via jejunostomy. Devices underwent 3 cycles of balloon inflation and hydraulic extension/retraction per day for 7 days and then explanted and studied for efficacy. RESULTS: DFM attachment allowed reversible, high-strength endoluminal coupling without tissue injury or reduction in bowel perfusion. After 7 day implant, distracted bowel achieved a 44 +/- 2% increase in length vs. fed, nondistracted bowel, corresponding to a gain of 7.1 +/- 0.3 cm. Distracted bowel demonstrated increased epithelial cell proliferation vs. control bowel. Attachment sites demonstrated villus flattening, increased crypt depth, thicker muscularis mucosa, and unchanged muscularis propria thickness vs. CONCLUSION: Novel high-strength, reversible attachments enabled fully endoluminal distraction enterogenesis, achieving length gains comparable to open surgical techniques. This approach may allow development of clinically applicable technology for SBS treatment. PMID- 26552896 TI - Endoscopic button gastrostomy: Comparing a sutured endoscopic approach to the current techniques. AB - PURPOSE: Button gastrostomy is the preferred feeding device in children and can be placed open or laparoscopically (LBG). Alternatively, a percutaneous endoscopic gastrostomy (PEG) can be placed initially and exchanged for a button. Endoscopic-assisted button gastrostomy (EBG) combines both techniques, using only one incision and suturing the stomach to the abdominal wall. The long-term outcomes and potential costs for EBG were compared to other techniques. METHODS: Children undergoing EBG, LBG, and PEG (2010-2013) were compared. Patient demographics, procedure duration/complications, and clinic and emergency room (ER) visits for an eight-week follow-up period were compared. RESULTS: Patient demographics were similar (32 patients/group). Mean procedure time (min) for EBG was 38 +/- 9, compared to 58 +/- 20 for LBG and 31 +/- 10 for PEG (p<0.0001). The most common complications were granulation tissue and infection with a trend toward fewer infections in EBG group. Average number of ER visits was similar, but PEG group had fewer clinic visits. 97% of PEG patients had subsequent visits for exchange to button gastrostomy. CONCLUSIONS: EBG is safe and comparable to LBG and PEG in terms of complications. It has a shorter procedure time than LBG and does not require laparoscopy, device exchange, or subsequent fluoroscopic confirmation, potentially reducing costs. PMID- 26552897 TI - Effect of cell seeding on neotissue formation in a tissue engineered trachea. AB - BACKGROUND: Surgical management of long segment tracheal disease is limited by a paucity of donor tissue and poor performance of synthetic materials. A potential solution is the development of a tissue-engineered tracheal graft (TETG) which promises an autologous airway conduit with growth capacity. METHODS: We created a TETG by vacuum seeding bone marrow-derived mononuclear cells (BM-MNCs) on a polymeric nanofiber scaffold. First, we evaluated the role of scaffold porosity on cell seeding efficiency in vitro. We then determined the effect of cell seeding on graft performance in vivo using an ovine model. RESULTS: Seeding efficiency of normal porosity (NP) grafts was significantly increased when compared to high porosity (HP) grafts (NP: 360.3 +/- 69.19 * 10(3) cells/mm(2); HP: 133.7 +/- 22.73 * 10(3) cells/mm(2); p<0.004). Lambs received unseeded (n=2) or seeded (n=3) NP scaffolds as tracheal interposition grafts for 6 weeks. Three animals were terminated early owing to respiratory complications (n=2 unseeded, n=1 seeded). Seeded TETG explants demonstrated wound healing, epithelial migration, and delayed stenosis when compared to their unseeded counterparts. CONCLUSION: Vacuum seeding BM-MNCs on nanofiber scaffolds for immediate implantation as tracheal interposition grafts is a viable approach to generate TETGs, but further preclinical research is warranted before advocating this technology for clinical application. PMID- 26552898 TI - Highly efficient hyperentanglement concentration with two steps assisted by quantum swap gates. AB - We present a two-step hyperentanglement concentration protocol (hyper-ECP) for polarization-spatial hyperentangled Bell states based on the high-capacity character of hyperentanglement resorting to the swap gates, which is used to obtain maximally hyperentangled states from partially hyperentangled pure states in long-distance quantum communication. The swap gate, which is constructed with the giant optical circular birefringence (GOCB) of a diamond nitrogen-vacancy (NV) center embedded in a photonic crystal cavity, can be used to transfer the information in one degree of freedom (DOF) between photon systems. By transferring the useful information between hyperentangled photon pairs, more photon pairs in maximally hyperentangled state can be obtained in our hyper-ECP, and the success probability of the hyper-ECP is greatly improved. Moreover, we show that the high-fidelity quantum gate operations can be achieved by mapping the infidelities to heralded losses even in the weak coupling regime. PMID- 26552899 TI - 2-Arylquinazolin-4(3H)-ones: A new class of alpha-glucosidase inhibitors. AB - Twenty-five derivatives of 2-arylquinazolin-4(3H)-ones (1-25) were evaluated for their yeast (Saccharomyces cerevisiae) alpha-glucosidase inhibitory activities. All synthetic compounds, except 1 and 6, were found to be several hundred fold more active (IC50 values in the range of 0.3+/-0.01-117.9+/-1.76MUM), than the standard drug, acarbose (IC50=840+/-1.73MUM). The enzyme kinetic studies on the most active compounds 12, 4, 19, and 13 were performed for the determination of their modes of inhibition and dissociation constants Ki. Study of the modes of inhibition of compounds 12, and 4 were also performed using molecular modeling techniques. In brief, current study identifies a novel class of alpha-glucosidase inhibitors which can be further studied for the treatment of hyperglycemia and obesity. PMID- 26552900 TI - Continuous-flow thermolysis for the preparation of vinylglycine derivatives. AB - Syn sulfoxide elimination was carried out under continuous-flow conditions in a mesofluidic thermolysis reactor. The design of the reactor enabled accurate control of reaction time and conditions, affording a convenient scale-independent procedure for the production of N,C-protected vinylglycine derivatives. Thermolysis at 270 degrees C under 1000 psi of pressure in superheated toluene enabled typical daily outputs ranging from 11 to 46 g per day with excellent selectivities and ee (>97%). The various competitive reaction pathways were studied and rationalized according to a computational study. PMID- 26552902 TI - How fast is the reaction of hydrated electrons with graphene oxide in aqueous dispersions? AB - Understanding the mechanism of the reduction of graphene oxide (GO) is a key question in graphene related materials science. Here, we investigate the kinetics of the reaction of radiolytically generated hydrated electrons with GO in water. The electron transfer proceeds on the ns time scale and not on the ps time scale, as recently reported by Gengler et al. (Nat. Commun., 2013, 4, 2560). PMID- 26552901 TI - A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions. AB - BACKGROUND: Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. RESULTS: Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. CONCLUSIONS: Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively. PMID- 26552903 TI - Cardioversion of atrial fibrillation or atrial flutter into sinus rhythm reduces nocturnal central respiratory events and unmasks obstructive sleep apnoea. AB - AIMS: Sleep-disordered breathing (SDB), in particular obstructive sleep apnoea, is associated with an increased risk of onset or recurrence of atrial fibrillation (AF) and atrial flutter. This prospective study investigated the relationship between restoration of sinus rhythm and SDB in patients with AF or atrial flutter. METHODS AND RESULTS: 138 consecutive patients (age 67.8 +/- 10.3 years, 67.4 % male) with AF (86.2 %) or atrial flutter (13.8 %) were enrolled and underwent multichannel cardiorespiratory polygraphy the night before and immediately after electrical cardioversion (CV). None of the patients was treated with ventilation therapy before or during the study. Overall prevalence of SDB [apnoea-hypopnoea index (AHI) >=5/h] was 92 % and prevalence of moderate-to severe SDB (AHI) >=15/h was 64 %. Within the first night after CV, AHI decreased from 23.4 +/- 16.3 to 16.3 +/- 11.5/h, p < 0.001. This was due to a significant decrease in central respiratory events, with a total reduction of patients showing central sleep apnoea (n = 53 at baseline vs n = 23 immediately after CV; p < 0.001). CONCLUSIONS: In conclusion, SDB represents a highly prevalent comorbidity in patients with atrial arrhythmias. Through cardioversion, an immediate reduction of SDB can be detected due to a significant reduction in central respiratory events. PMID- 26552904 TI - Antegrade transcatheter mitral valve-in-valve implantation with combined atrial septal defect closure. PMID- 26552905 TI - General practitioners' adherence to chronic heart failure guidelines regarding medication: the GP-HF study. AB - AIMS: The adherence to the guidelines for pharmacotherapy of chronic heart failure (HF)-patients improves prognosis. Although general practitioners (GPs) treat the majority of HF-patients, information about GPs' current guideline adherence and their typical prescription rationales is sparse. METHODS AND RESULTS: A three-stage study design was employed. In Stage I, 206 patient records from 15 randomly chosen GP practices were analysed; 76 % of patients were prescribed ACE-inhibitors or angiotensin receptor blockers (ACEIs/ARBs), 73 % beta blocker (BBs), but only 18 % mineralocorticoid receptor antagonists (MRAs). ACEI doses were at 62 % of the guideline recommended target doses, BBs at 46 %, while MRAs were sufficiently highly dosed. The guideline adherence indicator (GAI 3) was only 22 %. In Stage II, GPs in all 15 practices were interviewed, and health record documentation deficits and patients' contraindications were taken into account. This increased the percentage of patients correctly prescribed ACEIs/ARBs to 87 %, BBs to 84 % and GAI-3 to 56 %. MRAs exhibited the most frequent contraindications, but remained underprescribed. Many GPs seemed not to be aware of the therapeutic value of MRAs or the need to reach target doses of the indicated drug classes. Patients-interviewed in Stage III-reported good tolerability of HF-drugs and generally good compliance, although 11 % discontinued HF-medication on their own. CONCLUSIONS: Guideline adherence of GPs was higher than expected from literature and might be further improved by highlighting MRAs as the third prognostically relevant drug class beside ACEIs/ARBs and BBs and stronger emphasis on target doses. PMID- 26552906 TI - Prediction and validation of DXA-derived appendicular lean soft tissue mass by ultrasound in older adults. AB - The purpose of this study was to develop regression-based prediction equations for estimating dual-energy X-ray absorptiometry (DXA)-derived appendicular lean soft tissue mass (aLM) using ultrasound and to investigate the validity of these equations in 102 Caucasian adults aged 50 to 76 years. The subjects were randomly separated into two groups: 71 in the model-development group (41 men and 30 women) and 31 in the cross-validation group (18 men and 13 women). aLM was measured using a DXA, and muscle thickness (MT) was measured using ultrasound at 9 sites. Stepwise linear regression analysis was used to determine predictive models for DXA-derived aLM from MT variables, sex, and age. A number of ultrasound prediction equations for estimation of aLM were developed and then cross-validated in a subsample of older adults. The results indicated that ultrasound MT and MT * height can be used to accurately and reliably estimate DXA derived aLM in older Caucasian adults. PMID- 26552907 TI - Robotic-Assisted Surgery Improves the Quality of Total Mesorectal Excision for Rectal Cancer Compared to Laparoscopy: Results of a Case-Controlled Analysis. AB - BACKGROUND: The use of a robotic surgical system is claimed to allow precise traction and counter-traction, especially in a narrow pelvis. Whether this translates to improvement of the quality of the resected specimen is not yet clear. The aim of the study was to compare the quality of the TME and the short term oncological outcome between robotic and laparoscopic rectal cancer resections. METHODS: 20 consecutive robotic TME performed in a single institution for rectal cancer (Rob group) were matched 1:2 to 40 laparoscopic resections (Lap group) for gender, body mass index (BMI), and distance from anal verge on rigid proctoscopy. The quality of TME was assessed by 2 blinded and independent pathologists and reported according to international standardized guidelines. RESULTS: Both samples were well matched for gender, BMI (median 25.9 vs. 24.2 kg/m(2), p = 0.24), and level of the tumor (4.1 vs. 4.8 cm, p = 0.20). The quality of the TME was better in the Robotic group (complete TME: 95 vs. 55 %; p = 0.0003, nearly complete TME 5 vs. 37 %; p = 0.04, incomplete TME 0 vs. 8 %, p = 0.09). A trend for lower positive circumferential margin was observed in the Robotic group (10 vs. 25 %, p = 0.1). CONCLUSIONS: These results suggest that robotic-assisted surgery improves the quality of TME for rectal cancer. Whether this translates to better oncological outcome needs to be further investigated. PMID- 26552908 TI - Krukenberg Tumors of Gastric Origin: The Rationale of Surgical Resection and Perioperative Treatments in a Multicenter Western Experience. AB - BACKGROUND: In case of Krukenberg tumor (KT) of gastric origin it is controversial and debated whether radical surgery in case of synchronous KT or metastasectomy in case of metachronous ones is associated with additional benefits. Role of perioperative treatments is unclear. METHODS: Among 2515 female patients who were diagnosed with gastric cancer between January 1990 and December 2012 from 9 Italian centers, 63 presented simultaneously or developed KT as recurrence. RESULTS: Thirty patients presented with synchronous KT, while 33 developed metachronous ovarian metastases during follow-up. The differences between the two groups were analyzed and compared. The median age of 63 patients was 48.0 years (range 31-71). Resection was possible in 53 patients (20 synchronous and 33 metachronous). Twelve patients in the synchronous group and 15 patients of the metachronous group underwent hyperthermic intraperitoneal chemotherapy after resection of KT. All of them underwent adjuvant chemotherapy after KT resection. The median survival for all population was 23 months (95 % confidence interval, 7-39 months). The median survival time in the metachronous group was 36 months, which was significantly longer than that in the synchronous group, 17 months, p < 0.0001. CONCLUSIONS: KT remains a clinical challenge for gastric cancer therapy. The extent of disease and feasibility of removal of the metastatic lesion must be carefully evaluated prior to surgery to define the patients group who could benefit most from a resection associated with perioperative treatments. PMID- 26552909 TI - Using Transcutaneous Laryngeal Ultrasonography (TLUSG) to Assess Post thyroidectomy Patients' Vocal Cords: Which Maneuver Best Optimizes Visualization and Assessment Accuracy? AB - To assess vocal cord (VC) movement with transcutaneous laryngeal ultrasound (TLUSG), three maneuvers, namely passive (quiet respiration), active (phonation), and Valsalva maneuvers have been described. It remains unclear which maneuver or using more maneuvers provides better visualization and assessment accuracy. We prospectively evaluated 342 post-thyroidectomy patients from two centers. They underwent TLUSG with direct laryngoscopic (DL) validation afterwards. During TLUSG, patients were instructed to perform all three maneuvers (passive, active, and Valsalva). VC visualization rate and accuracy between three maneuvers were compared. Visualization rate tended to be higher in Valsalva maneuver than that in other two maneuvers (92.1% vs. passive: 91.5%; active: 89.8%). While 19 patients had post-operative VC palsy, passive maneuver had lower test specificity than active (94.3 vs. 97.6%, p = 0.01) and Valsalva maneuvers (94.3 vs. 97.4%, p = 0.02). In assessable VCs, passive maneuver has a higher ability to differentiate between mobile VCs and VC palsy (Area under ROC curve--passive: 0.942, active: 0.863, Valsalva: 0.893). TLUSG with more maneuvers did not improve sensitivity or specificity. On applying TLUSG as a screening tool (i.e., only selected patient with "unassessable" VCs or VCP on TLUSG for DL), Valsalva maneuver (85.96%) saved more patients from DL than passive (81.87%) or active (84.81%) maneuver. Passive maneuver has a higher ability to differentiate VC palsy from normal. Using TLUSG as a screening tool, Valsalva was the preferred maneuver as it was more specific, had high visualization rate, and saved more patients from DL. PMID- 26552910 TI - Parapharyngeal Metastasis of Papillary Thyroid Carcinoma. AB - BACKGROUND: Nodal involvement of papillary thyroid carcinoma (PTC) commonly occurs in the paratracheal region and the internal jugular chain. Lymph node metastasis in the parapharyngeal space (PPS) is rare. In this report, we describe our experience and surgical outcomes of patients with PPS metastasis of PTC. METHODS: Clinical data of patients with PTC who underwent surgery at our institution between January 2006 and December 2013 were retrospectively reviewed, and 22 patients with PPS metastasis were enrolled. RESULTS: There were 2 primary and 20 secondary cases of PPS metastasis. Involvement of the jugular nodes was noted before or at the time of PPS metastasis detection in all cases. A transcervical surgical approach with partial resection of the mandibular angle was performed in 21 patients, while 1 patient underwent extirpation of the PPS metastasis via a transoral approach. Although curative resection was performed in 21 patients, the PPS metastasis was not removable in 1 patient owing to an invaded internal carotid artery at the skull base. Twelve and 6 patients had locoregional and distant recurrence, respectively. Of the 12 patients with locoregional recurrence, isolated locoregional recurrence in the PPS occurred in 1. Eight patients died of distant or locoregional recurrence, with a median survival time of 91.7 months. CONCLUSIONS: For patients who experience recurrence after thyroid surgery, the possibility of PPS metastasis should be considered. In this series, all patients with PPS metastasis also had previous unilateral or bilateral cervical metastasis. Despite curative attempt, most patients experienced local or distant recurrence. PMID- 26552911 TI - Recurrent Laryngeal Nerve Liberations and Reconstructions: A Single Institution Experience. AB - BACKGROUND: Recurrent laryngeal nerve (RLN) palsy rates vary from 0.5 to 10%, even 20% in thyroid cancer surgery. The aim of this paper was to present our experience with RLN liberations and reconstructions after various mechanisms of injury. METHODS: Patients were treated in our institution from year 2000 to 2015. First group (27 patients) had large benign goiters, locally advanced thyroid/parathyroid carcinomas, or incomplete previous surgery of malignant thyroid disease. Second group (5 patients) had reoperations due to RLN paralysis on laryngoscopy. Liberations and reconstructions of injured RLNs were performed. RESULTS: Surgical exploration of central compartment enabled identification of the RLN injury mechanism. Liberations were performed in 11 patients, 2 months to 16 years after RLN injury, by removing misplaced ligations. Immediate or delayed (18 months to 23 years) RLN reconstructions were performed in 21 patients, by direct suture or ansa cervicalis-to-RLN anastomosis (ARA). RLN liberation provided complete voice recovery within 3 weeks in all patients. Patients with direct sutures had better phonation 1 month after reconstruction. Improved phonation was observed 2-6 months after ARA in 43% of patients. CONCLUSIONS: Vocal cords do not regain normal movement once being paralyzed after RLN transection, but they restore tension during phonation by reconstruction. Nerve liberation is a useful method which enables patients with RLN paresis/paralysis a significant improvement in phonation, even complete voice recovery. Reinnervation of vocal cords, using one of the mentioned techniques, should be a standard in thyroid and parathyroid surgery, with aim to improve quality of patient's life. PMID- 26552912 TI - Variation on a Theme: Alternative to Plastic Bag in ALPPS Procedures-Feasibility and Clinical Safety of COVA+TM Membrane in ALPPS Procedure. PMID- 26552913 TI - Evaluation of 64-Channel Contrast-Enhanced Multi-detector Row Computed Tomography for Preoperative N Staging in cT2-4 Gastric Carcinoma. AB - BACKGROUND: Preoperative N staging is essential for the best treatment planning in patients with gastric carcinoma. The aim of this study was to evaluate the accuracy of preoperative N staging using contrast-enhanced multi-detector row computed tomography (CE-MDCT) in patients with resectable cT2-4 gastric carcinoma. METHODS: A total of 218 patients who underwent a gastrectomy with D2 lymphadenectomy for previously untreated cT2-4 primary gastric carcinoma were studied. Preoperative N staging was performed according to the 7th (UICC) TNM Staging System using pre-specified criteria on a 64-channel CE-MDCT and was compared with postoperative pathologic N staging. RESULTS: In all 218 patients, a distal or total gastrectomy was performed. The overall accuracy of the preoperative N staging was 46.3% (101/218), with the proportion of over- and under-staging being 26.6% (58/218) and 27.1% (59/218), respectively. The sensitivity, specificity, and accuracy for lymph node metastasis (>=pN1) were 79.1% (106/134), 50.0% (42/84), and 67.9% (148/218), respectively. The sensitivity, specificity, and accuracy for multiple lymph node metastases (>=pN2) were 80.2% (73/91), 68.5% (87/127), and 73.4% (160/218), respectively. Multivariate analyses showed that macroscopic type 2 and >=6 cm-sized tumors were associated with preoperative over-N staging, while macroscopic type 1/3 tumors were associated with under-N staging. CONCLUSION: Preoperative N staging with pinpoint accuracy is difficult. However, CE-MDCT offers a reasonably high sensitivity and specificity for >=pN2 and may be useful for selecting candidates for neoadjuvant therapies. The macroscopic type and size of the primary tumor may affect the accuracy of preoperative N staging. PMID- 26552914 TI - Late Recurrence After Radical Resection of Esophageal Cancer. AB - BACKGROUND: Approximately 10-20 % of esophageal cancer patients in whom recurrence is diagnosed experience late recurrence beyond 2 years after esophagectomy. However, the risk of late recurrence is still unclear. The aim of this study was to identify the risk factors of late recurrence for appropriate postoperative surveillance. METHODS: A total of 447 patients underwent radical esophagectomy and reconstruction for esophageal cancer from 2005 to 2014. Patients who had recurrence beyond 2 years after esophagectomy were defined as the late recurrence group and the remaining patients with recurrence as the early recurrence group. A comparison of the clinicopathological factors and prognosis was performed between patients with early recurrence, late recurrence, and no recurrence. RESULTS: Recurrences were recognized in 117(26.2 %) of the 447 patients. Recurrence was diagnosed within 2 years after surgery in 103 patients (88.0 %) and after 2 years in 14 patients (12.0 %). Patients with late recurrence showed a favorable prognosis compared with those with early recurrence (P = 0.0131), and late recurrence was an independent factor associated with a favorable prognosis after recurrence (HR 0.199, P = 0.025). In the comparison between patients with late recurrence and those with no recurrence who had a minimal recurrence-free survival of 2 years, pathological lymph node metastasis at esophagectomy was found to be an independent predictor of late recurrence (HR 7.296, P = 0.043). CONCLUSIONS: Pathological lymph node metastasis at esophagectomy is a risk factor of late recurrence for esophageal cancer, and a close, lifelong follow-up is recommended for such patients. PMID- 26552916 TI - Portrait of Dr. Ted M. Ross. PMID- 26552915 TI - Effects of the Timing of Herbivory on Plant Defense Induction and Insect Performance in Ribwort Plantain (Plantago lanceolata L.) Depend on Plant Mycorrhizal Status. AB - Plants often are exposed to antagonistic and symbiotic organisms both aboveground and belowground. Interactions between above- and belowground organisms may occur either simultaneously or sequentially, and jointly can determine plant responses to future enemies. However, little is known about time-dependency of such aboveground-belowground interactions. We examined how the timing of a 24 h period of aboveground herbivory by Spodoptera exigua (1-8 d prior to later arriving conspecifics) influenced the response of Plantago lanceolata and the performance of later arriving conspecifics. We also examined whether these induced responses were modulated by the arbuscular mycorrhizal fungus (AMF) Funneliformis mosseae. The amount of leaf area consumed by later arriving herbivores decreased with time after induction by early herbivores. Mycorrhizal infection reduced the relative growth rate (RGR) of later arriving herbivores, associated with a reduction in efficiency of conversion of ingested food rather than a reduction in relative consumption rates. In non-mycorrhizal plants, leaf concentrations of the defense compound catalpol showed a linear two-fold increase during the eight days following early herbivory. By contrast, mycorrhizal plants already had elevated levels of leaf catalpol prior to their exposure to early herbivory and did not show any further increase following herbivory. These results indicate that AMF resulted in a systemic induction, rather than priming of these defenses. AMF infection significantly reduced shoot biomass of Plantago lanceolata. We conclude that plant responses to future herbivores are not only influenced by exposure to prior aboveground and belowground organisms, but also by when these prior organisms arrive and interact. PMID- 26552917 TI - Granulation of Non-filamentous Bulking Sludge Directed by pH, ORP and DO in an Anaerobic/Aerobic/Anoxic SBR. AB - In an anaerobic/aerobic/anoxic (A/O/A) sequencing batch reactor (SBR), non filamentous bulking sludge granulated after the adjustment of cycle duration and influent composition directed by pH, oxidation-reduction potential (ORP) and dissolved oxygen (DO). The turning points and plateaux of pH, ORP and DO profiles indicated the end of biochemical reactions, such as chemical oxygen demand (COD) consumption, P release, ammonium oxidation, P uptake and denitrification. The difference of nutrient concentration between the beginning and turning points represented the actual treatment capability of the sludge. Non-filamentous bulking with SVI30 of 255 mL g(-1) resulted in a huge biomass loss. After regulation, the cycle duration was shortened from 310 to 195 min without unnecessary energy input. In addition, the settling ability was obviously improved as SVI30 reduced to 28 mL g(-1). Moreover, matured granules with an average diameter of 600 MUm were obtained after 45 days, and simultaneous COD, ammonium and phosphate (P) removal was also realized after granulation. PMID- 26552918 TI - A rare case of ulcerative colitis exacerbated by VZV infection. AB - A 16-years old man with severe ulcerative colitis (UC) was admitted to our hospital. After initiating treatment with corticosteroid for UC, chicken pox appeared. At the same time of appearance of chicken pox, the disease activity of UC was exacerbated. After initiating the treatment with acyclovir, both chicken pox and UC improved. Because colonoscopic findings revealed the remaining of moderately active UC, initiating the treatment with infliximab could induce clinical remission of UC without relapse of varicella-zoster virus (VZV) infection. This is a very rare case of UC with concomitant VZV infection. According to our report, the vaccination for VZV prior to immunosuppressive treatments would be necessary for VZV naive patients with UC. PMID- 26552920 TI - [Requirements for mycological diagnostics in accordance with the guideline of the German Medical Association for quality assurance of medical laboratory tests]. AB - The ability of recognizing various clinical manifestations of mucocutaneous mycosis, making a diagnosis, and establishing a treatment is part of a dermatologist's daily routine. However, due to the fact that clinical manifestations, laboratory diagnostics, and treatment are performed in one hand, laboratory findings are properly classified and interpreted. Since new binding guidelines of the German Medical Association on quality assurance measures in medical laboratory testing came into force, there is much concern among dermatologists of how to comply with these new regulations. It is the intention of the authors to help our readers to implement these new rules in order to make sure that mycological diagnostics continue to be part of a dermatologist's professional work. PMID- 26552919 TI - Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by celastrol. AB - BACKGROUND: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention. METHODS AND RESULTS: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-kappaB inhibition and transient mTOR activation: these two events occurred prior to miR 223 elevation in celastrol-treated cells. NF-kappaB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-kappaB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-kappaB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not. CONCLUSIONS: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti cancer effects. PMID- 26552921 TI - Extracorporeal therapies in pediatric severe sepsis: findings from the pediatric health-care information system. AB - INTRODUCTION: Pediatric severe sepsis (PSS) continues to be a major health problem. Extracorporeal therapies (ETs), defined as extracorporeal membrane oxygenation (ECMO) and RRenal replacement therapyenal replacement therapy (RRT), are becoming more available for utilization in a variety of health conditions. We aim to describe (1) rates of utilization of ET in PSS, (2) outcomes for PSS patients receiving ET, and (3) epidemiologic characteristics of patients receiving ET. METHODS: We conducted a retrospective review of a prospectively collected database. Data from the Pediatric Health Information System (PHIS) database collected by the Children's Hospital Association (CHA) from 2004-2012 from 43 US children's hospitals' pediatric intensive care units (PICUs) were used. Patients with PSS were defined by (1) International Classification of Diseases, 9th Revision (ICD-9) codes reflecting severe sepsis and septic shock and (2) ICD-9 codes of infection and organ dysfunction as defined by updated Angus criteria. Among the patients with PSS, those with a PHIS flag of ECMO or RRT were identified further as our main cohort. RESULTS: From 2004 to 2012, 636,842 patients were identified from 43 hospitals, and PSS prevalence was 7.7 % (49,153 patients). Nine point eight percent (4795 patients) received at least one form of ET, and the associated mortality rate was 39 %. Mortality rates were 47.8 % for those who received ECMO, 32.3 % in RRT, and 58.0 % in RRT + ECMO. Underlying co-morbidities were found in 3745 patients (78.1 %) who received ET (81 % for ECMO, 77.9 % in RRT, and 71.2 % in those who received both). There was a statistically significant increase in ECMO utilization in patients with at least three organ dysfunctions from 2004 to 2012 (6.9 % versus 10.3 %, P < 0.001) while RRT use declined (24.5 % versus 13.2 %, P < 0.001). After 2009, there was a significant increase in ECMO utilization (3.6 % in 2004-2008 versus 4.0 % in 2009 2012, P = 0.004). ECMO and RRT were used simultaneously in only 500 patients with PSS (1 %). CONCLUSIONS: ETs were used in a significant portion of PSS patients with multiple organ dysfunction syndrome (MODS) during this time period. Mortality was significant and increased with increasing organ failure. ECMO use in PSS patients with MODS increased from 2004 to 2012. Further evaluation of ET use in PSS is warranted. PMID- 26552922 TI - A novel N-terminal region of the membrane beta-hexosyltransferase: its role in secretion of soluble protein by Pichia pastoris. AB - The beta-hexosyltransferase (BHT) from Sporobolomyces singularis is a membrane bound enzyme that catalyses transgalactosylation reactions to synthesize galacto oligosaccharides (GOSs). To increase the secretion of the active soluble version of this protein, we examined the uncharacterized novel N-terminal region (amino acids 1-110), which included two predicted endogenous structural domains. The first domain (amino acids 1-22) may act as a classical leader while a non classical signal was located within the remaining region (amino acids 23-110). A functional analysis of these domains was performed by evaluating the amounts of the rBHT forms secreted by recombinant P. pastoris strains carrying combinations of the predicted structural domains and the alpha mating factor (MFalpha) from Saccharomyces cerevisiae as positive control. Upon replacement of the leader domain (amino acids 1-22) by MFalpha (MFalpha-rBht(23-594)), protein secretion increased and activity of both soluble and membrane-bound enzymes was improved 53 and 14-fold, respectively. Leader interference was demonstrated when MFalpha preceded the putative classical rBHT(1-22) leader (amino acids 1-22), explaining the limited secretion of soluble protein by P. pastoris (GS115 : : MFalpha-rBht(1 594)). To validate the role of the N-terminal domains in promoting protein secretion, we tested the domains using a non-secreted protein, the anti-beta galactosidase single-chain variable antibody fragment scFv13R4. The recombinants carrying chimeras of the N-terminal 1-110 regions of rBHT preceding scFv13R4 correlated with the secretion strength of soluble protein observed with the rBHT recombinants. Finally, soluble bioactive HIS-tagged and non-tagged rBHT (purified to homogeneity) obtained from the most efficient recombinants (GS115 : : MFalpha rBht(23-594)-HIS and GS115 : : MFalpha-rBht(23-594)) showed comparable activity rates of GOS generation. PMID- 26552924 TI - [A new dawn for psychiatry: focus on early detection and prevention of severe mental illness]. PMID- 26552923 TI - A grid matrix-based Raman spectroscopic method to characterize different cell milieu in biopsied axillary sentinel lymph nodes of breast cancer patients. AB - Raman spectroscopy which is based upon inelastic scattering of photons has a potential to emerge as a noninvasive bedside in vivo or ex vivo molecular diagnostic tool. There is a need to improve the sensitivity and predictability of Raman spectroscopy. We developed a grid matrix-based tissue mapping protocol to acquire cellular-specific spectra that also involved digital microscopy for localizing malignant and lymphocytic cells in sentinel lymph node biopsy sample. Biosignals acquired from specific cellular milieu were subjected to an advanced supervised analytical method, i.e., cross-correlation and peak-to-peak ratio in addition to PCA and PC-LDA. We observed decreased spectral intensity as well as shift in the spectral peaks of amides and lipid bands in the completely metastatic (cancer cells) lymph nodes with high cellular density. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to create an automated smart diagnostic tool for bench side screening of sampled lymph nodes. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to develop an automated smart diagnostic tool for bench side screening of sampled lymph nodes supported by ongoing global research in developing better technology and signal and big data processing algorithms. PMID- 26552925 TI - [The attitude of the general public towards (discharged) psychiatric patients: results from NEMESIS-2]. AB - BACKGROUND: In the Netherlands there is no up-to-date information about the attitude of the public to (discharged) psychiatric patients. Also, very little is known about which population groups hold stigmatising views. AIM: To measure the public's attitudes to (discharged) psychiatric patients and to find out whether these attitudes differ according to the background characteristics (e.g. demographics, respondent's psychiatric history). METHOD: In our study we used attitudes collected via the Netherlands Mental Health Survey and Incidence Study 2, a psychiatric epidemiological study of the adult general population (n = 6646; aged 18-64 years). The psychiatric history of the respondents was assessed by means of the Composite International Diagnostic Interview 3.0. RESULTS: More than 70% of the respondents stated that they had no objection to having a (discharged) psychiatric patient as a neighbour, friend or colleague. However, their 'willingness' declined markedly, namely to less than 30%, when they were asked if they would be willing to have a (discharged) psychiatric patient as their son-in law or baby-sitter. A comparison with other earlier Dutch studies indicates that since 1987 the willingness of members of the public to let (ex-)psychiatric patients participate in their private and/or family life has increased only very slightly. CONCLUSION: Nowadays, just as in past decades, most Dutch citizens are not opposed to living alongside (discharged) psychiatric patients, but they have reservations about letting such persons participate in their private and family life. PMID- 26552926 TI - [Depression during the perimenopause]. AB - BACKGROUND: Women are believed to be more vulnerable to depression during the perimenopause than during the premenopausal period. In clinical practice little attention has been given to the relationship between the menopause and depression. AIM: To provide an overview of the literature on the relationship between the perimenopause and the development of depression and to analyse the relationship between hormonal fluctuations and depression. METHOD: We consulted the databases of PubMed, Web of Science and the Cochrane library, searching for epidemiologic studies on perimenopausal depression. We selected 22 studies relating to the prevalence of and the risk of depression during perimenopause. RESULTS: Most of the 22 epidemiological studies selected suggest that the chances of developing depression during the perimenopause are higher than during during the premenopausal period. We found no unambiguous correlation between the fluctuation of hormones (e.g. oestrogen) and depression. A possible reason for this finding is that it is difficult to measure these hormones accurately. CONCLUSION: The chances of developing depression seem to be higher during the perimenopause than during the premenopause. The difficulty in measuring the fluctuations of female hormones during the perimenopausal stage may be the reason why no correlation between depression and the fluctuations of hormones has yet been unambiguously established. Future studies and meta-analysis could provide a more accurate estimate of the risk of developing depression during the perimenopause and could give detailed information about the relationship between hormonal factors and perimenopausal depression. PMID- 26552927 TI - [Early-onset eating disorders: a review of the literature]. AB - BACKGROUND: The incidence of anorexia nervosa (AN) in adolescents has increased significantly in recent years. In several studies and in the media it has been suggested that AN has recently become more prevalent in the pre-adolescence. In view of the impact that an eating disorder can have on a child, it is important to diagnose and start treating the illness as early as possible. AIM: To review the literature on the characteristics and susceptibilities of patients with eating disorders because this information can be important for early diagnosis, prevention and identification of susceptibilities to early-onset eating disorders. METHOD: We searched the literature for articles relating to early onset eating disorders. We based our search on PubMed and on related relevant articles listed in the references. We selected 34 relevant articles published between 1987 and 2014. RESULTS: The literature lists characteristics and susceptibilities at various levels. Many types of factors are involved; examples of 'biological' factors are prior streptococcal infection, previous consultations with GP and a patients medical history; psychological factors include comorbidity, temperament, a particular personality profile, maturation-anxiety; environmental factors such as family history, family functioning and/or stressful events can play a role in the development of eating disorders. CONCLUSION The literature indicates that the early development of AN in children is related to a complex combination of etiological factors. However, there is a need for more research into this group of patients. PMID- 26552928 TI - [Functional recovery and self-regulation: assignments for both clients and psychiatrists]. AB - BACKGROUND: Currently, attention is focused on recovery, but the concept is under discussion. The functional aspect, i.e. the re-establishment and development of mental functions, is rarely explained in mental health care. As a result, certain opportunities may be missed, particularly with regard to helping clients to develop or restore their self-regulatory abilities. AIM: To clarify what we mean by functional recovery and to explain why it is important to deal with this theme separately and to distinguish between functioning and mental functions. METHOD: An overview is given of current developments in and around mental health care, and the true meaning of the concept of recovery is discussed. Furthermore, arguments are presented which stress the usefulness of distinguishing between four aspects of recovery: clinical, personal, social and functional. RESULTS: As is still the case in regular health care (rehabilitation), the subject of functional recovery is hardly ever dealt with as a separate entity. If it were to be dealt with separately and if attention were to be given particularly to the executive functions and their significance for self-regulation, fresh opportunities would arise for supporting clients in their recovery process. CONCLUSION: If functional recovery is dealt with separately, new opportunities for recovery will arise, even if clinical recovery is no longer a viable option. The use of the International Classification of Functioning, Disability and Health (ICF) can ensure that focus in the future will shift to the recovery of psychosocial functioning and mental functions. PMID- 26552929 TI - [Music therapy and depression]. AB - BACKGROUND: Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. AIM: To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. METHOD: We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. RESULTS: A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. CONCLUSION: Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy. PMID- 26552930 TI - [Amisulpride: a treatment option for psychotic disorders soon to be available in the Netherlands]. AB - BACKGROUND: The antipsychotic drug amisulpride has not yet been officially approved for use in the Netherlands, although it is already available in other European countries , including Belgium, the UK and Germany. However, a fast-track procedure has recently been initiated so that amisulpride will soon become available in the Netherlands as well. AIM: To summarise the efficacy and side effects of amisulpride. METHOD: We discuss the evidence presented in the scientific literature. RESULTS: The scientific literature assures us that amisulpride is an effective antipsychotic drug with an acceptable range of side effects. This means that there are two main advantages that ensue from the use of amisulpride: a patient's psychosis is more likely to go into remission and patients are less likely to stop taking the drug. CONCLUSION: The availability of amisulpride in the Netherlands will constitute a valuable addition to the pharmacotherapeutic options for treating psychotic disorders in our county. PMID- 26552932 TI - [Admitting and caring for refugees. Can their sense of self-worth be reclaimed?]. PMID- 26552931 TI - [Hypomania following the use of varenicline in two patients with bipolar disorder]. AB - Varenicline is a drug that has been developed to help people stop smoking . Results regarding its efficacy are promising. The safety of the drug, however, is controversial when used for patients with mental illnesses because it can have neuropsychiatric side-effects. Although Dutch guidelines and the 'Farmacotherapeutisch Kompas' include warnings about the use of varenicline by people with severe mental illness, the drug is still being prescribed for this group of patients. This is not without risk. We illustrate this point by focusing on two patients with bipolar disorder who developed manic symptoms while using varenicline. We discuss relevant literature and make recommendations. PMID- 26552934 TI - Electron Beam Induced Artifacts During in situ TEM Deformation of Nanostructured Metals. AB - A critical assumption underlying in situ transmission electron microscopy studies is that the electron beam (e-beam) exposure does not fundamentally alter the intrinsic deformation behavior of the materials being probed. Here, we show that e-beam exposure causes increased dislocation activation and marked stress relaxation in aluminum and gold films spanning a range of thicknesses (80-400 nanometers) and grain sizes (50-220 nanometers). Furthermore, the e-beam induces anomalous sample necking, which unusually depends more on the e-beam diameter than intensity. Notably, the stress relaxation in both aluminum and gold occurs at beam energies well below their damage thresholds. More remarkably, the stress relaxation and/or sample necking is significantly more pronounced at lower accelerating voltages (120 kV versus 200 kV) in both the metals. These observations in aluminum and gold, two metals with highly dissimilar atomic weights and properties, indicate that e-beam exposure can cause anomalous behavior in a broad spectrum of nanostructured materials, and simultaneously suggest a strategy to minimize such artifacts. PMID- 26552935 TI - Insomnia is associated with suicide attempt in middle-aged and older adults with depression. AB - BACKGROUND: Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35). METHODS: Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable. RESULTS: The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder. CONCLUSIONS: Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults. PMID- 26552936 TI - Enhancement of the catalytic efficiency and thermostability of Stenotrophomonas sp. keratinase KerSMD by domain exchange with KerSMF. AB - In this study, we enhanced the catalytic efficiency and thermostability of keratinase KerSMD by replacing its N/C-terminal domains with those from a homologous protease, KerSMF, to degrade feather waste. Replacement of the N terminal domain generated a mutant protein with more than twofold increased catalytic activity towards casein. Replacement of the C-terminal domain obviously improved keratinolytic activity and increased the k(cat)/K(m) value on a synthetic peptide, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, by 54.5%. Replacement of both the N- and C-terminal domains generated a more stable mutant protein, with a Tm value of 64.60 +/- 0.65 degrees C and a half-life of 244.6 +/- 2 min at 60 degrees C, while deletion of the C-terminal domain from KerSMD or KerSMF resulted in mutant proteins exhibiting high activity under mesophilic conditions. These findings indicate that the pre-peptidase C-terminal domain and N-propeptide are not only important for substrate specificity, correct folding and thermostability but also support the ability of the enzyme to convert feather waste into feed additives. PMID- 26552937 TI - Probing the interactions of CdTe quantum dots with pseudorabies virus. AB - Quantum dots (QDs) have become one of the most promising luminescent materials for tracking viral infection in living cells. However, several issues regarding how QDs interact with the virus remain unresolved. Herein, the effects of Glutathione (GSH) capped CdTe QDs on virus were investigated by using pseudorabies virus (PRV) as a model. One-step growth curve and fluorescence colocalization analyses indicate that CdTe QDs inhibit PRV multiplication in the early stage of virus replication cycle by suppressing the invasion, but have no significant effect on the PRV penetration. Fluorescence spectrum analysis indicates that the size of QDs is reduced gradually after the addition of PRV within 30 min. Release of Cd(2+) was detected during the interaction of QDs and PRV, resulting in a decreased number of viruses which can infect cells. Further Raman spectra and Circular Dichroism (CD) spectroscopy analyses reveal that the structure of viral surface proteins is altered by CdTe QDs adsorbed on the virus surface, leading to the inhibition of virus replication. This study facilitates an in-depth understanding of the pathogenic mechanism of viruses and provides a basis for QDs-labeled virus research. PMID- 26552938 TI - Application of a hot-melt granulation process to enhance fenofibrate solid dose manufacturing. AB - Evaluation of hot-melt granulation of fenofibrate and croscarmellose sodium and its cooling time for the molten mass in a ratio of 55:45 was conducted to assess the manufacturing process capability to produce an acceptable granulation which flows well on Korsch PH300 tablet compression machine. The formation of the drug polymer eutectic mixture was investigated by differential scanning calorimetry, scanning electron microscopy and X-ray powder diffraction. The physical properties of the hot-melt was determined by examining the milled blocks after solidification and milling after cooling periods of 10, 20 and 30 d. The milled material was assessed for the effect of hold time of the blend on the solid dose compression characteristics. The impact of cooling on the processing of the blocks was assessed after 10, 20 and 30 d of cooling. The study suggests that after the hot-melt formed the fenofibrate crystallized independently and a solid solution with croscarmellose sodium was not formed. The age of the blocks determined the hardness of the crystals, changing the processing nature of the granules with respect to compression and powder flow characteristics. The blocks processed after 20 d and beyond produced granules with a characteristic suitable for holding the blend for 14 d in the bin with no impact on flow properties and compressibility of the blend. There was no chipping, capping, sticking or picking observed and a higher compression speed was achieved. PMID- 26552939 TI - Increased homocysteine levels exist in women with preeclampsia from early pregnancy. AB - OBJECTIVE: The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery. METHODS: The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology. RESULTS: Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01). CONCLUSION: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery. PMID- 26552940 TI - Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder. AB - OBJECTIVE: Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder. METHOD: The authors searched PubMed for randomized placebo controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder. RESULTS: Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: beta=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: beta=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta regression: beta=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54). CONCLUSIONS: Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses. PMID- 26552941 TI - Transformation of Mental Health Care for U.S. Soldiers and Families During the Iraq and Afghanistan Wars: Where Science and Politics Intersect. AB - The cumulative strain of 14 years of war on service members, veterans, and their families, together with continuing global threats and the unique stresses of military service, are likely to be felt for years to come. Scientific as well as political factors have influenced how the military has addressed the mental health needs resulting from these wars. Two important differences between mental health care delivered during the Iraq and Afghanistan wars and previous wars are the degree to which research has directly informed care and the consolidated management of services. The U.S. Army Medical Command implemented programmatic changes to ensure delivery of high-quality standardized mental health services, including centralized workload management; consolidation of psychiatry, psychology, psychiatric nursing, and social work services under integrated behavioral health departments; creation of satellite mental health clinics embedded within brigade work areas; incorporation of mental health providers into primary care; routine mental health screening throughout soldiers' careers; standardization of clinical outcome measures; and improved services for family members. This transformation has been accompanied by reduction in psychiatric hospitalizations and improved continuity of care. Challenges remain, however, including continued underutilization of services by those most in need, problems with treatment of substance use disorders, overuse of opioid medications, concerns with the structure of care for chronic postdeployment (including postconcussion) symptoms, and ongoing questions concerning the causes of historically high suicide rates, efficacy of resilience training initiatives, and research priorities. It is critical to ensure that remaining gaps are addressed and that knowledge gained during these wars is retained and further evolved. PMID- 26552942 TI - Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features: A Randomized, Double-Blind, Placebo-Controlled Study. AB - OBJECTIVE: Accumulating evidence indicates that manic symptoms below the threshold for hypomania (mixed features) are common in individuals with major depressive disorder. This form of depression is often severe and is associated with an increased risk for recurrence, suicide attempts, substance abuse, and functional disability. This study evaluated the efficacy and safety of lurasidone in major depressive disorder with mixed features. METHODS: Patients meeting DSM IV-TR criteria for major depressive disorder who presented with two or three protocol-defined manic symptoms were randomly assigned to 6 weeks of double-blind treatment with either lurasidone at 20-60 mg/day (N=109) or placebo (N=100). Changes from baseline in Montgomery-Asberg Depression Rating Scale score (MADRS; primary outcome measure) and Clinical Global Impressions severity subscale score (CGI-S; key secondary outcome measure) were evaluated using a mixed model for repeated-measures analysis. RESULTS: Lurasidone significantly improved depressive symptoms and overall illness severity, assessed by least squares mean change at week 6 in the MADRS and CGI-S scores: -20.5 compared with -13.0 (effect size, 0.80) and -1.8 compared with -1.2 (effect size, 0.60), respectively. Significant improvement in manic symptoms, assessed by the Young Mania Rating Scale, was also observed, in addition to other secondary efficacy endpoints. Rates of discontinuation due to adverse events were low. The most common adverse events were nausea (6.4% and 2.0% in the lurasidone and placebo groups, respectively) and somnolence (5.5% and 1.0%). CONCLUSIONS: Lurasidone was effective and well tolerated in this study involving patients with major depressive disorder associated with subthreshold hypomanic symptoms (mixed features). PMID- 26552943 TI - Modeling crowdsourcing as collective problem solving. AB - Crowdsourcing is a process of accumulating the ideas, thoughts or information from many independent participants, with aim to find the best solution for a given challenge. Modern information technologies allow for massive number of subjects to be involved in a more or less spontaneous way. Still, the full potentials of crowdsourcing are yet to be reached. We introduce a modeling framework through which we study the effectiveness of crowdsourcing in relation to the level of collectivism in facing the problem. Our findings reveal an intricate relationship between the number of participants and the difficulty of the problem, indicating the optimal size of the crowdsourced group. We discuss our results in the context of modern utilization of crowdsourcing. PMID- 26552944 TI - Recovery time for inflamed middle ear mucosa in chronic otitis media. AB - CONCLUSION: The present study shows that 2-3 weeks after medical treatment the status of middle ear mucosa in draining ears is similar to that of dry ears for at least 3 months. OBJECTIVE: To measure the time required for an inflamed middle ear mucosa to return into optimal state after appropriate medical treatment in chronic suppurative otitis media (CSOM). To assess optimal timing for elective surgical treatment of draining ears in uncomplicated CSOM. METHODS: In this prospective study, the Eustachian tube (ET) mucociliary clearance time (MCT) was used as the method to demonstrate the status of middle ear mucosa. In group 1 (28 patients) ET-MCT was measured in ears that were free of drainage for at least 3 months. In Group 2 (21 patients), ET-MCT was measured in draining ears, who responded to 10-14 days medical treatment, at presentation, after 10 days and 1 month. RESULTS: The ET-MCT was 8.63 +/- 1.32 min in group 1 and 28.96 +/- 8.19 min in group 2 at presentation; and the difference was statistically significant (p < 0.001). The ET-MCT was 14.76 +/- 5.11 min after 10 days and 9.31 +/- 2.33 min after 1 month in group 2. The ET-MCT was indifferent between groups 1 and 2 after 1 month (p = 0.235). PMID- 26552945 TI - A Tale of Two Systems: Combining Forces to Improve Veteran and Military Health Care. PMID- 26552946 TI - No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child. AB - BACKGROUND: Sweden has the second highest incidence of type 1 diabetes in the world. Nutritional aspects in utero and in infancy affect the development. We conducted a survey to determine whether reported maternal use of vitamin D containing micronutrient supplements during pregnancy was associated with the risk of developing type 1 diabetes in the child. METHODS: This report was based on data from the ABIS (All Babies In Southeast Sweden) study, with questionnaire data on 16 339 mother and infant pairs at birth and at 1-yr of age (n = 10 879), of whom 108 children were registered with type 1 diabetes before 14-16 yr of age. The questions 'during pregnancy, did you take any vitamin/mineral supplements?' and 'if yes, which? (open answer)' in addition to other lifestyle questions were answered. Logistic regression was performed with onset of type 1 diabetes as the dependent variable and vitamin D supplementation use as the independent variable, adjusted for relevant factors. RESULTS: Vitamin D supplementation during pregnancy was consumed by 9.3% of mothers whose children later got type1 diabetes and among 11.3% of those mothers whose children did not get type 1 diabetes (p = 0.532). No significant association was found between reported supplement intake of vitamin D during pregnancy and risk of type 1 diabetes, even when adjusting for factors which could influence the association. CONCLUSION: Maternal use of vitamin D-containing multivitamin supplements during pregnancy was not related to the risk of developing type 1 diabetes in children before 14-16 yr of age in Southeast of Sweden. PMID- 26552947 TI - Suicide risk assessment and intervention in people with mental illness. AB - Suicide is the 15th most common cause of death worldwide. Although relatively uncommon in the general population, suicide rates are much higher in people with mental health problems. Clinicians often have to assess and manage suicide risk. Risk assessment is challenging for several reasons, not least because conventional approaches to risk assessment rely on patient self reporting and suicidal patients may wish to conceal their plans. Accurate methods of predicting suicide therefore remain elusive and are actively being studied. Novel approaches to risk assessment have shown promise, including empirically derived tools and implicit association tests. Service provision for suicidal patients is often substandard, particularly at times of highest need, such as after discharge from hospital or the emergency department. Although several drug based and psychotherapy based treatments exist, the best approaches to reducing the risk of suicide are still unclear. Some of the most compelling evidence supports long established treatments such as lithium and cognitive behavioral therapy. Emerging options include ketamine and internet based psychotherapies. This review summarizes the current science in suicide risk assessment and provides an overview of the interventions shown to reduce the risk of suicide, with a focus on the clinical management of people with mental disorders. PMID- 26552948 TI - Chemically Lithiated TiO2 Heterostructured Nanosheet Anode with Excellent Rate Capability and Long Cycle Life for High-Performance Lithium-Ion Batteries. AB - A new form of dual-phase heterostructured nanosheet comprised of oxygen-deficient TiO2/Li4Ti5O12 has been successfully synthesized and used as anode material for lithium ion batteries. With the three-dimensional (3D) Ti mesh as both the conducting substrate and the Ti(3+)/Ti(4+) source, blue anatase Ti(3+)/TiO2nanosheets were grown by a hydrothermal reaction. By controlling the chemical lithiation period of TiO2 nanosheets, a phase boundary was created between the TiO2 and the newly formed Li4Ti5O12, which contribute additional capacity benefiting from favorable charge separation between the two phase interfaces. Through further hydrogenation of the 3D TiO2/Li4Ti5O12 heterostructured nanosheets (denoted as H-TiO2/LTO HNS), an extraordinary rate performance with capacity of 174 mAh g(-1) at 200 C and outstanding long-term cycling stability with only an ~6% decrease of its initial specific capacity after 6000 cycles were delivered. The heterostructured nanosheet morphology provides a short length of lithium diffusion and high electrode/electrolyte contact area, which could also explain the remarkable lithium storage performance. In addition, the full battery assembled based on the H-TiO2/LTO anode achieves high energy and power densities. PMID- 26552949 TI - Physiological Expression and Accumulation of the Products of Two Upstream Open Reading Frames mrtl and MycHex1 Along With p64 and p67 Myc From the Human c-myc Locus. AB - In addition to the canonical c-Myc p64 and p67 proteins, the human c-myc locus encodes two distinct proteins, mrtl (myc-related translation/localization regulatory factor) and MycHex1 (Myc Human Exon 1), from the upstream open reading frames within the 5'-untranslated region of the c-myc P0 mRNA. The aim of this study is to examine simultaneously, for the first time, mrtl, MycHex1, c-Myc p64, and p67 in human tumor cell lines and pediatric brain tumor tissues. Western blot analysis demonstrated endogenous mrtl, MycHex1, c-Myc p64, and p67 simultaneously. The relative abundance of mrtl and MycHex1 were consistent among a variety of human tumor cell lines, and the relative intensities of mrtl and MycHex1 correlated positively. Confocal imaging revealed mrtl predominantly localized to the nuclear envelope, along with prominent reticular pattern in the cytoplasm. MycHex1 was observed as a series of bright foci located within the nucleus, a subset of which colocalized with fibrillarin. mrtl and MycHex1 co immunoprecipitated with RACK1, c-Myc, fibrillarin, coilin, and with each other. These findings suggest that mrtl and MycHex1 have multiple interaction partners in both the nucleus and cytoplasm. Sequence analyses confirmed a known polymorphism of mrtl at base 1965 (G>T) and new mutations at bases 1900 (C>G) and 1798 (C>G). Evidence is presented for expression and stable accumulation of all four proteins encoded by three distinct non-overlapping open reading frames within the human c-myc locus. Additional work is warranted to further elucidate the functional or regulatory roles of these molecules in regulation of c-Myc and in oncogenesis. PMID- 26552950 TI - CHAARTED/GETUG 12--docetaxel in non-castrate prostate cancers. PMID- 26552951 TI - Colorectal cancer: Targeting BRAF mutations equally? PMID- 26552954 TI - Adjuvant TKIs in NSCLC: what can we learn from RADIANT? PMID- 26552957 TI - Chemotherapy and the recurrence score--results as expected? PMID- 26552953 TI - The changing landscape of phase I trials in oncology. AB - Advances in our knowledge of the molecular pathogenesis of cancer have led to increased interest in molecularly targeted agents (MTAs), which target specific oncogenic drivers and are now a major focus of cancer drug development. MTAs differ from traditional cytotoxic agents in various aspects, including their toxicity profiles and the potential availability of predictive biomarkers of response. The landscape of phase I oncology trials is evolving to adapt to these novel therapies and to improve the efficiency of drug development. In this Review, we discuss new strategies used in phase I trial design, such as novel dose-escalation schemes to circumvent limitations of the classic 3 + 3 design and enable faster dose escalation and/or more-precise dose determinations using statistical modelling; improved selection of patients based on genetic or molecular biomarkers; pharmacokinetic and pharmacodynamic analyses; and the early evaluation of efficacy - in addition to safety. Indeed, new expedited approval pathways that can accelerate drug development require demonstration of efficacy in early phase trials. The application of molecular tumour profiling for matched therapy and the testing of drug combinations based on a strong biological rationale are also increasingly seen in phase I studies. Finally, the shift towards multi-institutional trials and centralized study management results in consequent implications for institutions and investigators. These issues are also highlighted herein. PMID- 26552959 TI - CheckMate for advanced-stage ccRCC? Nivolumab and cabozantinib aMETEORate poor survival. PMID- 26552960 TI - Cell signalling: Truncation to expansion - a new indication for ALK inhibition? PMID- 26552962 TI - The need to revisit published data: A concept and framework for complementary proteomics. AB - Tandem proteomic strategies based on large-scale and high-resolution mass spectrometry have been widely applied in various biomedical studies. However, protein sequence databases and proteomic software are continuously updated. Proteomic studies should not be ended with a stable list of proteins. It is necessary and beneficial to regularly revise the results. Besides, the original proteomic studies usually focused on a limited aspect of protein information and valuable information may remain undiscovered in the raw spectra. Several studies have reported novel findings by reanalyzing previously published raw data. However, there are still no standard guidelines for comprehensive reanalysis. In the present study, we proposed the concept and draft framework for complementary proteomics, which are aimed to revise protein list or mine new discoveries by revisiting published data. PMID- 26552961 TI - Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure. AB - Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats. PMID- 26552963 TI - Topical therapy for psoriasis: a promising future. Focus on JAK and phosphodiesterase-4 inhibitors. AB - Psoriasis is a common, chronic and disabling skin disorder affecting approximately 2% of the population, associated with significant negative impact on the patient's quality of life. Approximately 80% of those affected with psoriasis have mild-to-moderate forms and are usually treated with topical therapy, whereas phototherapy and systemic therapies are used for those with severe disease. In the past three decades, the major advances in psoriasis therapy have been in systemic agents for the treatment of moderate-to-severe psoriasis, particularly new immunomodulatory and biological molecules, while topical therapies have remained relatively unchanged over the past decades. Indeed, topical corticosteroids and vitamin D3 analogs are still the gold standard of therapy for mild-to-moderate psoriasis. Thus, there is a need to develop new and more effective topical agents in the short and long term, with a better efficacy and safety profile than corticosteroids and vitamin D3 analogs. Over the past five years, investigation into topical therapy has expanded, with exciting new drugs being developed. Preliminary results of these emerging agents that selectively target disease-defining pathogenic pathways seem to be promising, although long-term and large-scale studies assessing safety and efficacy are still lacking. The aim of this article was to review the clinical and research data of some emerging topical agents, focusing on Janus kinase signal transducer and activator of transcription and phosphodiesterase type 4 inhibitors, which are currently being investigated. PMID- 26552964 TI - Fast-moving dislocations trigger flash weakening in carbonate-bearing faults during earthquakes. AB - Rupture fronts can cause fault displacement, reaching speeds up to several ms(-1) within a few milliseconds, at any distance away from the earthquake nucleation area. In the case of silicate-bearing rocks the abrupt slip acceleration results in melting at asperity contacts causing a large reduction in fault frictional strength (i.e., flash weakening). Flash weakening is also observed in experiments performed in carbonate-bearing rocks but evidence for melting is lacking. To unravel the micro-physical mechanisms associated with flash weakening in carbonates, experiments were conducted on pre-cut Carrara marble cylinders using a rotary shear apparatus at conditions relevant to earthquakes propagation. In the first 5 mm of slip the shear stress was reduced up to 30% and CO2 was released. Focused ion beam, scanning and transmission electron microscopy investigations of the slipping zones reveal the presence of calcite nanograins and amorphous carbon. We interpret the CO2 release, the formation of nanograins and amorphous carbon to be the result of a shock-like stress release associated with the migration of fast-moving dislocations. Amorphous carbon, given its low friction coefficient, is responsible for flash weakening and promotes the propagation of the seismic rupture in carbonate-bearing fault patches. PMID- 26552965 TI - Prevalence and predictors of tobacco use in the elderly. AB - OBJECTIVE: Smoking is a well-established public health issue, which has not been examined previously among the elderly in Singapore. This paper describes and identifies the current prevalence and predictors of tobacco use among the older resident population. METHODS: Data were derived from the Well-being of the Singapore Elderly study, a cross-sectional epidemiological study of the elderly in Singapore. Sociodemographic data from 2565 Singapore residents aged 60 years and above were collected through face-to-face interviews. Multinomial logistic regression analyses identified predictors of tobacco use. RESULTS: A total of 236 respondents were current tobacco users (9.5%). The majority of older tobacco users were men (88.1%). Significant predictors of tobacco use were gender, marital status, and education level. Younger age (60-74 years old) was associated with more tobacco use, and the completion of tertiary education with lower rates of use. CONCLUSIONS: Smoking prevalence among the elderly was lower than that of the Singapore general adult population (16%). However, the rate is still high and is of concern given the likelihood of a higher rate of physical disorders, which could be worsened with tobacco use. The identification of those at risk enables them to be targeted for smoking cessation programs and other interventions. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26552966 TI - Phytoremediation of lead-contaminated soil by Sinapis arvensis and Rapistrum rugosum. AB - Nowadays, public concern relating to ecological deleterious effects of heavy metals is on the rise. To evaluate the potential of Rapistrum rugosum and Sinapis arvensis in lead- contaminate phytoremediate, a pot culture experiment was conducted. The pots were filled by soil treated with different rates of leadoxide (PbO) including 0 (control), 100, 200, 300, 400, and 500 mg Pb per 1 kg soil. Germinated seeds were sown. Surprisingly, with increasing concentration of Pb, dry weight of R. rugosum and S. arvensis did not decrease significantly. In both of species, the concentration of Pb was higher in roots than shoots. In general, S.arvensis was absorbed more Pb compared to R. rugosum. The results revealed high potential of R. rugosum and S. arvensis in withdrawing Pb from contaminated soil. For both species, a positive linear relation was observed between Pb concentration in soil and roots. However, linear relationship was not observed between Pb concentration in the soil and shoots. Although both species test had low ability in translocation Pb from roots to shoots but they showed high ability in uptake soil Pb by roots. Apparently, these plants are proper species for using in phytoremediation technology. PMID- 26552967 TI - 2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL. AB - BACKGROUND: Cancer cells survival depends on glucose metabolism and ATP. Inhibiting glucose metabolism is a possible anticancer treatment. The phosphorylation of 2-deoxy-D-glucose (2-DG), which is a glycogen analogue, seriously affects the normal glycometabolism phosphorylation process, leading to ATP consumption. Studies showed that 2-DG could regulate RIP and c-FLIP. This paper aimed to investigate the effect of 2-DG on RIP and c-FLIP expression in HepG2 and Hep3B cells, further illustrating the effect and mechanism of 2-DG regulating RIP and c-FLIP expression on liver cancer cell apoptosis induced by TRAIL. MATERIAL AND METHODS: RIP and c-FLIP gene silencing HepG2 and Hep3B cell models were established by siRNA and detected by Western blot. Cell viability was determined by MTT and apoptosis rate was measured by flow cytometry. JC-1 fluorescent probe was used to test mitochondrial membrane potential. RESULTS: 2 DG or TRAIL alone significantly reduced HepG2 and Hep3B cell survival rate and promoted apoptosis. Compared with the single TRAIL treatment group, the combination of 2-DG and TRAIL could reduce cell survival rate, increase apoptosis rate, and decease mitochondrial membrane potential, which is dependent on Caspases. 2-DG can inhibit RIP and c-FLIP expression, leading to increased TRAIL induced HepG2 and Hep3B cells apoptosis. CONCLUSIONS: 2-DG can down-regulate RIP and c-FLIP expression, and change Caspases activities to increase the liver cancer cell apoptosis induced by TRAIL. PMID- 26552968 TI - Efficacy of Extended-Interval Dosing of Micafungin Evaluated Using a Pharmacokinetic/Pharmacodynamic Study with Humanized Doses in Mice. AB - The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of the echinocandins favor infrequent administration of large doses. The in vivo investigation reported here tested the utility of a range of humanized dose levels of micafungin using a variety of prolonged dosing intervals for the prevention and therapy of established disseminated candidiasis. Humanized doses of 600 mg administered every 6 days prevented fungal growth in prophylaxis. Humanized doses of 300 to 1,000 mg administered every 6 days demonstrated efficacy for established infections. PMID- 26552970 TI - Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae. AB - We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options. PMID- 26552969 TI - Antimicrobial Peptide CMA3 Derived from the CA-MA Hybrid Peptide: Antibacterial and Anti-inflammatory Activities with Low Cytotoxicity and Mechanism of Action in Escherichia coli. AB - CA-MA is a hybrid antimicrobial peptide (AMP) derived from two naturally occurring AMPs, cecropin A and magainin 2. CA-MA shows strong antimicrobial activity against Gram-negative and Gram-positive bacteria but also exhibits cytotoxicity toward mammalian cells. Our objective was to identify CA-MA analogues with reduced cytotoxicity by systematic replacement of amino acids with positively charged R groups (His and Lys), aliphatic R groups (Leu), or polar R groups (Glu). Among the CA-MA analogues studied (CMA1 to -6), CMA3 showed the strongest antimicrobial activity, including against drug-resistant Escherichia coli and Pseudomonas aeruginosa strains isolated from hospital patients. CMA3 appeared to act by inducing pore formation (toroidal model) in the bacterial membrane. In cytotoxicity assays, CMA3 showed little cytotoxicity toward human red blood cells (hRBCs) or HaCaT cells. Additionally, no fluorescence was released from small or giant unilamellar vesicles exposed to 60 MUM CMA3 for 80 s, whereas fluorescence was released within 35 s upon exposure to CA-MA. CMA3 also exerted strong lipopolysaccharide (LPS)-neutralizing activity in RAW 264.7 cells, and BALB/c mice exposed to LPS after infection by Escherichia coli showed improved survival after administration of one 0.5-mg/kg of body weight or 1-mg/kg dose of CMA3. Finally, in a mouse model of septic shock, CMA3 reduced the levels of proinflammatory factors, including both nitric oxide and white blood cells, and correspondingly reduced lung tissue damage. This study suggests that CMA3 is an antimicrobial/antiendotoxin peptide that could serve as the basis for the development of anti-inflammatory and/or antimicrobial agents with low cytotoxicity. PMID- 26552971 TI - In Vitro Activity of Ceftolozane-Tazobactam against Anaerobic Organisms Identified during the ASPECT-cIAI Study. AB - The in vitro activities of ceftolozane-tazobactam, meropenem, and metronidazole were determined against anaerobic organisms isolated from patients with complicated intraabdominal infections (cIAI) in global phase III studies. Ceftolozane-tazobactam activity was highly variable among different species of the Bacteroides fragilis group, with MIC90 values ranging from 2 to 64 MUg/ml. More-potent in vitro activity was observed against selected Gram-positive anaerobic organisms; however, small numbers of isolates were available, and, therefore, the clinical significance of these results is unknown. Variable activity of ceftolozane-tazobactam against anaerobic organisms necessitates use in combination with metronidazole for the treatment of cIAI. PMID- 26552972 TI - Model-Based Evaluation of Higher Doses of Rifampin Using a Semimechanistic Model Incorporating Autoinduction and Saturation of Hepatic Extraction. AB - Rifampin is a key sterilizing drug in the treatment of tuberculosis (TB). It induces its own metabolism, but neither the onset nor the extent of autoinduction has been adequately described. Currently, the World Health Organization recommends a rifampin dose of 8 to 12 mg/kg of body weight, which is believed to be suboptimal, and higher doses may potentially improve treatment outcomes. However, a nonlinear increase in exposure may be observed because of saturation of hepatic extraction and hence this should be taken into consideration when a dose increase is implemented. Intensive pharmacokinetic (PK) data from 61 HIV-TB coinfected patients in South Africa were collected at four visits, on days 1, 8, 15, and 29, after initiation of treatment. Data were analyzed by population nonlinear mixed-effects modeling. Rifampin PKs were best described by using a transit compartment absorption and a well-stirred liver model with saturation of hepatic extraction, including a first-pass effect. Autoinduction was characterized by using an exponential-maturation model: hepatic clearance almost doubled from the baseline to steady state, with a half-life of around 4.5 days. The model predicts that increases in the dose of rifampin result in more-than linear drug exposure increases as measured by the 24-h area under the concentration-time curve. Simulations with doses of up to 35 mg/kg produced results closely in line with those of clinical trials. PMID- 26552973 TI - In Vitro Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms. AB - ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against Aspergillus and Candida glabrata. We compared its in vitro activity against wild-type and azole resistant A. fumigatus and A. terreus isolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-type A. fumigatus isolates, 24 A. fumigatus isolates with alterations in CYP51A TR/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), and A. terreus isolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC50 values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) against A. fumigatus CYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistant A. fumigatus isolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active against A. terreus CYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayed in vitro activity against A. fumigatus and A. terreus isolates which was independent of the presence or absence of azole target gene resistance mutations in A. fumigatus. The findings are promising at a time when azole-resistant A. fumigatus is emerging globally. PMID- 26552974 TI - Carriage of Enterobacteria Producing Extended-Spectrum beta-Lactamases and Composition of the Gut Microbiota in an Amerindian Community. AB - Epidemiological and individual risk factors for colonization by enterobacteria producing extended-spectrum beta-lactamases (E-ESBL) have been studied extensively, but whether such colonization is associated with significant changes in the composition of the rest of the microbiota is still unknown. To address this issue, we assessed in an isolated Amerindian Guianese community whether intestinal carriage of E-ESBL was associated with specificities in gut microbiota using metagenomic and metatranscriptomic approaches. While the richness of taxa of the active microbiota of carriers was similar to that of noncarriers, the taxa were less homogeneous. In addition, species of four genera, Desulfovibrio, Oscillospira, Parabacteroides, and Coprococcus, were significantly more abundant in the active microbiota of noncarriers than in the active microbiota of carriers, whereas such was the case only for species of Desulfovibrio and Oscillospira in the total microbiota. Differential genera in noncarrier microbiota could either be associated with resistance to colonization or be the consequence of the colonization by E-ESBL. PMID- 26552975 TI - Pharmacodynamics of Ceftolozane plus Tazobactam Studied in an In Vitro Pharmacokinetic Model of Infection. AB - Ceftolozane plus tazobactam is an antipseudomonal cephalosporin combined with tazobactam, an established beta-lactamase inhibitor, and has in vitro potency against a range of clinically important beta-lactamase-producing bacteria, including most extended-spectrum-beta-lactamase (ESBL)-positive Enterobacteriaceae. The pharmacodynamics of beta-lactam-beta-lactamase inhibitor combinations presents a number of theoretical and practical challenges, including modeling different half-lives of the compounds. In this study, we studied the pharmacodynamics of ceftolozane plus tazobactam against Escherichia coli and Pseudomonas aeruginosa using an in vitro pharmacokinetic model of infection. Five strains of E. coli, including three clinical strains plus two CTX-M-15 (one high and one moderate) producers, and five strains of P. aeruginosa, including two with OprD overexpression and AmpC beta-lactamases, were employed. Ceftolozane MICs (E. coli, 0.12 to 0.25 mg/liter, and P. aeruginosa, 0.38 to 8 mg/liter) were determined in the presence of 4 mg/liter tazobactam. Dose ranging of ceftolozane (percentage of time in which the free-drug concentration exceeds the MIC [fT>MIC], 0 to 100%) plus tazobactam (human pharmacokinetics) was simulated every 8 hours, with half-lives (t1/2) of 2.5 and 1 h, respectively. Ceftolozane and tazobactam concentrations were confirmed by high-performance liquid chromatography (HPLC). The ceftolozane-plus-tazobactam fT>MIC values at 24 h for a static effect and a 1-log and 2-log drop in initial inoculum for E. coli were 27.8% +/- 5.6%, 33.0% +/- 5.6%, and 39.6% +/- 8.5%, respectively. CTX-M-15 production did not affect the 24-h fT>MIC for E. coli strains. The ceftolozane plus-tazobactam fT>MIC values for a 24-h static effect and a 1-log and 2-log drop for P. aeruginosa were 24.9% +/- 3.0%, 26.6% +/- 3.9%, and 31.2% +/- 3.6%. Despite a wide range of absolute MICs, the killing remained predictable as long as the MICs were normalized to the corresponding fT>MIC. Emergence of resistance on 4* MIC plates and 8* MIC plates occurred maximally at an fT>MIC of 10 to 30% and increased as time of exposure increased. The fT>MIC for a static effect for ceftolozane plus tazobactam is less than that observed with other cephalosporins against E. coli and P. aeruginosa and is more similar to the fT>MIC reported for carbapenems. PMID- 26552976 TI - Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli. AB - Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205; collected in 2004 to 2013) and food-producing animals (n = 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 MUg/ml to 34.3 MUg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 MUg/ml to 256 MUg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump. PMID- 26552977 TI - Effect of Meropenem Concentration on the Detection of Low Numbers of Carbapenem Resistant Enterobacteriaceae. PMID- 26552978 TI - Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children. AB - The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of >=50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean +/- standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 +/- 3 years, 17 +/- 6.2 kg, and 118 +/- 41 ml/min/1.73 m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam were as follows: clearance, 0.22 +/- 0.07 and 0.19 +/- 0.07 liter/h/kg, respectively; volume of distribution, 0.43 +/- 0.16 and 0.37 +/- 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of <=16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of >=80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children. PMID- 26552979 TI - High Prevalence of Biocide Resistance Determinants in Staphylococcus aureus Isolates from Three African Countries. AB - We assessed the prevalence of six biocide resistance genes among 82 methicillin resistant Staphylococcus aureus (MRSA) and 219 methicillin-susceptible S. aureus (MSSA) isolates from three African countries; the prevalence was very high for sepA (95.3%), mepA (89.4%), and norA (86.4%), intermediate for lmrS (60.8%) and qacAB (40.5%), and low for smr (3.7%). A significant association between biocide resistance genes and antibiotic resistance was observed, and a new cutoff MIC of >=1 mg/liter for chlorhexidine nonsusceptibility was defined. PMID- 26552980 TI - Azole Resistance in Aspergillus fumigatus Clinical Isolates from an Italian Culture Collection. AB - The aims of the study were to investigate the prevalence of azole resistance among Aspergillus fumigatus clinical isolates. A total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. No resistance was detected in isolates collected between 1995 and 1997. Starting in 1998, the resistance rate was 6.9%; a total of 24 patients (6.25%) harbored a resistant isolate. The TR34/L98H substitution was found in 21 of 30 tested isolates. PMID- 26552981 TI - Susceptibility of Clostridium difficile Isolates of Varying Antimicrobial Resistance Phenotypes to SMT19969 and 11 Comparators. AB - We determined the in vitro activity of SMT19969 and 11 comparators, including metronidazole, vancomycin, and fidaxomicin, against 107 C. difficile isolates of different antimicrobial resistance phenotypes. Fidaxomicin and SMT19969 were the most active. The fidaxomicin and SMT19969 geometric mean MICs were highest in ribotypes known to show multiple resistance. Coresistance to linezolid and moxifloxacin was evident in ribotypes 001, 017, 027, and 356. The high-level ceftriaxone resistance in ribotypes 356 and 018 was location linked. PMID- 26552982 TI - Extracellular DNA Acidifies Biofilms and Induces Aminoglycoside Resistance in Pseudomonas aeruginosa. AB - Biofilms consist of surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, exopolysaccharides, and proteins. Extracellular DNA (eDNA) has a structural role in the formation of biofilms, can bind and shield biofilms from aminoglycosides, and induces antimicrobial peptide resistance mechanisms. Here, we provide evidence that eDNA is responsible for the acidification of Pseudomonas aeruginosa planktonic cultures and biofilms. Further, we show that acidic pH and acidification via eDNA constitute a signal that is perceived by P. aeruginosa to induce the expression of genes regulated by the PhoPQ and PmrAB two-component regulatory systems. Planktonic P. aeruginosa cultured in exogenous 0.2% DNA or under acidic conditions demonstrates a 2- to 8 fold increase in aminoglycoside resistance. This resistance phenotype requires the aminoarabinose modification of lipid A and the production of spermidine on the bacterial outer membrane, which likely reduce the entry of aminoglycosides. Interestingly, the additions of the basic amino acid L-arginine and sodium bicarbonate neutralize the pH and restore P. aeruginosa susceptibility to aminoglycosides, even in the presence of eDNA. These data illustrate that the accumulation of eDNA in biofilms and infection sites can acidify the local environment and that acidic pH promotes the P. aeruginosa antibiotic resistance phenotype. PMID- 26552983 TI - Insights into the Molecular Mechanism of Polymerization and Nucleoside Reverse Transcriptase Inhibitor Incorporation by Human PrimPol. AB - Human PrimPol is a newly identified DNA and RNA primase-polymerase of the archaeo eukaryotic primase (AEP) superfamily and only the second known polymerase in the mitochondria. Mechanistic studies have shown that interactions of the primary mitochondrial DNA polymerase gamma (mtDNA Pol gamma) with nucleoside reverse transcriptase inhibitors (NRTIs), key components in treating HIV infection, are a major source of NRTI-associated toxicity. Understanding the interactions of host polymerases with antiviral and anticancer nucleoside analog therapies is critical for preventing life-threatening adverse events, particularly in AIDS patients who undergo lifelong treatment. Since PrimPol has only recently been discovered, the molecular mechanism of polymerization and incorporation of natural nucleotide and NRTI substrates, crucial for assessing the potential for PrimPol-mediated NRTI associated toxicity, has not been explored. We report for the first time a transient-kinetic analysis of polymerization for each nucleotide and NRTI substrate as catalyzed by PrimPol. These studies reveal that nucleotide selectivity limits chemical catalysis while the release of the elongated DNA product is the overall rate-limiting step. Remarkably, PrimPol incorporates four of the eight FDA-approved antiviral NRTIs with a kinetic profile distinct from that of mtDNA Pol gamma that may manifest in toxicity. PMID- 26552984 TI - fosI Is a New Integron-Associated Gene Cassette Encoding Reduced Susceptibility to Fosfomycin. AB - In this work, we demonstrate that the fosI gene encodes a predicted small protein with 134 amino acids and determines reduced susceptibility to fosfomycin. It raised the MIC from 0.125 to 6 MUg/ml when the pBRA100 plasmid was introduced into Escherichia coli TOP10 and to 16 MUg/ml when the gene was cloned into the pBC_SK(-) vector and expressed in E. coli TOP10. PMID- 26552985 TI - C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge. AB - A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID- 26552986 TI - Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture. AB - Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C. parvum CDPK1 and block C. parvum growth in tissue culture in vitro. Although these compounds potently inhibited kinase activity in vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in Toxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for C. parvum host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in C. parvum that are worthy of further exploration. PMID- 26552987 TI - Interactions of OP0595, a Novel Triple-Action Diazabicyclooctane, with beta Lactams against OP0595-Resistant Enterobacteriaceae Mutants. AB - OP0595 is a novel diazabicyclooctane which, like avibactam, inhibits class A and C beta-lactamases. In addition, unlike avibactam, it has antibacterial activity, with MICs of 0.5 to 4 MUg/ml for most members of the family Enterobacteriaceae, owing to inhibition of PBP2; moreover, it acts synergistically with PBP3-active beta-lactams independently of beta-lactamase inhibition, via an "enhancer effect." Enterobacteriaceae mutants stably resistant to 16 MUg/ml OP0595 were selected on agar at frequencies of approximately 10(-7). Unsurprisingly, OP0595 continued to potentiate substrate beta-lactams against mutants derived from Enterobacteriaceae with OP0595-inhibited class A and C beta-lactamases. Weaker potentiation of partners, especially aztreonam, cefepime, and piperacillin--less so meropenem--remained frequent for OP0595-resistant Enterobacteriaceae mutants lacking beta-lactamases or with OP0595-resistant metallo-beta-lactamases (MBLs), indicating that the enhancer effect is substantially retained even when antibiotic activity is lost. PMID- 26552988 TI - Heterologous Expression and Functional Characterization of the Exogenously Acquired Aminoglycoside Resistance Methyltransferases RmtD, RmtD2, and RmtG. AB - The exogenously acquired 16S rRNA methyltransferases RmtD, RmtD2, and RmtG were cloned and heterologously expressed in Escherichia coli, and the recombinant proteins were purified to near homogeneity. Each methyltransferase conferred an aminoglycoside resistance profile consistent with m(7)G1405 modification, and this activity was confirmed by in vitro 30S methylation assays. Analyses of protein structure and interaction with S-adenosyl-l-methionine suggest that the molecular mechanisms of substrate recognition and catalysis are conserved across the 16S rRNA (m(7)G1405) methyltransferase family. PMID- 26552990 TI - Doubly curved nanofiber-reinforced optically transparent composites. AB - Doubly curved nanofiber-reinforced optically transparent composites with low thermal expansion of 15 ppm/k are prepared by hot pressing vacuum-filtered Pickering emulsions of hydrophobic acrylic resin monomer, hydrophilic chitin nanofibers and water. The coalescence of acrylic monomer droplets in the emulsion is prevented by the chitin nanofibers network. This transparent composite has 3D shape moldability, making it attractive for optical precision parts. PMID- 26552989 TI - Structure and function of the septum nasi and the underlying tension chord in crocodylians. AB - A long rostrum has distinct advantages for prey capture in an aquatic or semi aquatic environment but at the same time poses severe problems concerning stability during biting. We here investigate the role of the septum nasi of brevirostrine crocodilians for load-absorption during mastication. Histologically, both the septum nasi and the septum interorbitale consist of hyaline cartilage and therefore mainly resist compression. However, we identified a strand of tissue extending longitudinally below the septum nasi that is characterized by a high content of collagenous and elastic fibers and could therefore resist tensile stresses. This strand of tissue is connected with the m. pterygoideus anterior. Two-dimensional finite element modeling shows that minimization of bending in the crocodilian skull can only be achieved if tensile stresses are counteracted by a strand of tissue. We propose that the newly identified strand of tissue acts as an active tension chord necessary for stabilizing the long rostrum of crocodilians during biting by transforming the high bending stress of the rostrum into moderate compressive stress. PMID- 26552991 TI - The heterocyst differentiation transcriptional regulator HetR of the filamentous cyanobacterium Anabaena forms tetramers and can be regulated by phosphorylation. AB - Many filamentous cyanobacteria respond to the external cue of nitrogen scarcity by the differentiation of heterocysts, cells specialized in the fixation of atmospheric nitrogen in oxic environments. Heterocysts follow a spatial pattern along the filament of two heterocysts separated by ca. 10-15 vegetative cells performing oxygenic photosynthesis. HetR is a transcriptional regulator that directs heterocyst differentiation. In the model strain Anabaena sp. PCC 7120, the HetR protein was observed in various oligomeric forms in vivo, including a tetramer that peaked with maximal hetR expression during differentiation. Tetramers were not detected in a hetR point mutant incapable of differentiation, but were conspicuous in an over-differentiating strain lacking the PatS inhibitor. In differentiated filaments the HetR tetramer was restricted to heterocysts, being undetectable in vegetative cells. HetR co-purified with RNA polymerase from Anabaena mainly as a tetramer. In vitro, purified recombinant HetR was distributed between monomers, dimers, trimers and tetramers, and it was phosphorylated when incubated with (gamma-(32)P)ATP. Phosphorylation and PatS hampered the accumulation of HetR tetramers and impaired HetR binding to DNA. In summary, tetrameric HetR appears to represent a functionally relevant form of HetR, whose abundance in the Anabaena filament could be negatively regulated by phosphorylation and by PatS. PMID- 26552992 TI - Which one of the two common reporter systems is more suitable for chemiluminescent enzyme immunoassay: alkaline phosphatase or horseradish peroxidase? AB - Alkaline phosphatase and horseradish peroxidase are the most commonly used reporter systems in chemiluminescent enzyme immunoassay (CLEIA). Which one, therefore, would be better when establishing a CLEIA method for a new target substance? There was no standard answer. In this study, both reporters were compared systematically including luminescence kinetics, conjugation methods, optimal condition and detection performance, using two common drugs, SD-methoxy pyrimidine and enrofloxacin, as determination objects. The results revealed that there was much difference between the luminescence kinetics of the two systems. However, there was little difference between these systems when detecting the same substance, including in optimal conditions and determination of performance. Both reporters were suitable for establishing chemiluminescent enzyme immunoassays. Therefore, the choice of alkaline phosphatase or horseradish peroxidase as the reporter system in chemiluminescent enzyme immunoassays depends on availability. Conversely, these two report systems could be applied in simultaneous analysis of multicomponents due to their different optical behaviors and similar performances. But attention should be paid to conjugation method and coating buffer, which affected the luminescent intensity of different determination targets. PMID- 26552993 TI - Flood Risk, Flood Mitigation, and Location Choice: Evaluating the National Flood Insurance Program's Community Rating System. AB - Climate change is expected to worsen the negative effects of natural disasters like floods. The negative impacts, however, can be mitigated by individuals' adjustments through migration and relocation behaviors. Previous literature has identified flood risk as one significant driver in relocation decisions, but no prior study examines the effect of the National Flood Insurance Program's voluntary program-the Community Rating System (CRS)-on residential location choice. This article fills this gap and tests the hypothesis that flood risk and the CRS-creditable flood control activities affect residential location choices. We employ a two-stage sorting model to empirically estimate the effects. In the first stage, individuals' risk perception and preference heterogeneity for the CRS activities are considered, while mean effects of flood risk and the CRS activities are estimated in the second stage. We then estimate heterogeneous marginal willingness to pay (WTP) for the CRS activities by category. Results show that age, ethnicity and race, educational attainment, and prior exposure to risk explain risk perception. We find significant values for the CRS-creditable mitigation activities, which provides empirical evidence for the benefits associated with the program. The marginal WTP for an additional credit point earned for public information activities, including hazard disclosure, is found to be the highest. Results also suggest that water amenities dominate flood risk. Thus, high amenity values may increase exposure to flood risk, and flood mitigation projects should be strategized in coastal regions accordingly. PMID- 26552994 TI - The 'cause' of my cancer, beliefs about cause among breast cancer patients and survivors who do and do not seek IO care. AB - OBJECTIVE: We sought to describe survivors' beliefs about the cause of their breast cancer and to test the hypothesis that beliefs about cancer's cause are associated with treatment preferences in accordance with the common sense model of self-regulation of health and illness. METHODS: Breast cancer survivors (n = 552) participating in an observational study of cancer outcomes responded to an open-ended question about the cause of their cancer. Of these, 245 women had sought treatment from complementary and alternative integrative oncology (IO) clinics, and 307 women did not. RESULTS: Women frequently described theories for their cancer's cause including genetics and family history (31%), stress and coping (31%), toxins and chemicals (27%), a variety of lifestyle and epidemiological risk factors, and randomness (17%). Self-reported beliefs about cancer's cause differed among women in association with their use of IO. IO users were somewhat more likely to describe stress and poor coping as causes of their cancer and less likely to describe random chance as a cause of cancer (p < 0.05). CONCLUSIONS: Beliefs about the cause of cancer change over time and may predict decisions to use specific treatment including complementary and alternative medicine and IO. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26552995 TI - Prevalence and severity of gingivitis in school students aged 6-11 years in Tafelah Governorate, South Jordan: results of the survey executed by National Woman's Health Care Center. AB - BACKGROUND: A cross-sectional census was conducted on 994 public school students aged 6-11 years living in 3 different parts of Tafeleh Governorate-South of Jordan, to determine the prevalence, and severity of gingivitis and to evaluate the oral hygiene habits among them as a part a survey executed by National Woman's Health Care Center. All students were examined for gingival index (GI) and plaque index (PI), information about oral hygiene habits was recorded. RESULTS: Only 29.8 % had healthy gingiva, 38.5 % had mild gingivitis, 31.4 % had moderate gingivitis, and 0.3 % had severe gingivitis. The difference between both genders was not statistically significant P > 0.05. 36.8 % of the examined students never brushed their teeth. Average gingival index (GI) and average plaque index (PI) were 0.77 and 0.61 respectively. CONCLUSIONS: Fair oral hygiene with mild to moderate gingivitis is highly prevalent among Tafelah school children. This study indicated that oral health status among schoolchildren in Tafelah is poor and needs to be improved. Long-term school based oral health education programme is highly recommended. PMID- 26552996 TI - First and repeat liver resection for primary and recurrent intrahepatic cholangiocarcinoma. AB - BACKGROUND: Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. METHODS: Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. RESULTS: The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P <= .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). CONCLUSIONS: Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival. PMID- 26552997 TI - Influence of preoperative magnetic resonance imaging on the surgical management of breast cancer patients. AB - BACKGROUND: Magnetic resonance imaging (MRI) is gaining popularity in the preoperative management of breast cancer patients. However, the role of this modality remains controversial. We aimed to study the impact of preoperative MRI (pMRI) on the surgical management of breast cancer patients. METHODS: This retrospective study included 766 subjects with breast cancer treated operatively at the specialized academic center. RESULTS: Between those who underwent pMRI (MRI group, n = 307) and those who did not (no-MRI group, n = 458), there were no significant differences (P = .254) in the proportions of either total mastectomies (20.5% vs 17.2%, respectively) or segmental mastectomies (79.5% vs 82.8%). Patients in the MRI group were significantly more likely (P = .002) to undergo contralateral surgery (11.7% vs 5.5%). Similar results were obtained in multivariate analysis adjusting for age, with the proportions of contralateral breast operations significantly higher in the MRI group (Odds Ratio = 2.25, P = .007). pMRI had no significant effect (P = .54) on the proportion of total re excisions (7.5% vs 8.7%) or the type of re-excision (total vs segmental mastectomy) between the groups. CONCLUSIONS: pMRI does not have a significant impact on the type of operative intervention on the ipsilateral breast but is associated with an increase in contralateral operations. Similarly, pMRI does not change the proportion of re-excisions or the type of the re-excision performed. This study demonstrates that pMRI has little impact on the surgical management of breast cancer, and its value as a routine adjunct in the preoperative work-up of recently diagnosed breast cancer patients needs to be re-examined. PMID- 26552998 TI - Is moral bioenhancement dangerous? AB - In a recent response to Persson and Savulescu's Unfit for the Future, Nicholas Agar argues that moral bioenhancement is dangerous. His grounds for this are that normal moral judgement should be privileged because it involves a balance of moral subcapacities; moral bioenhancement, Agar argues, involves the enhancement of only particular moral subcapacities, and thus upsets the balance inherent in normal moral judgement. Mistaken moral judgements, he says, are likely to result. I argue that Agar's argument fails for two reasons. First, having strength in a particular moral subcapacity does not necessarily entail a worsening of moral judgement; it can involve strength in a particular aspect of morality. Second, normal moral judgement is not sufficiently likely to be correct to be the standard by which moral judgements are measured. PMID- 26552999 TI - Indeterminacy and the normative basis of the harm threshold for overriding parental decisions: a response to Birchley. AB - Birchley's critique of the harm threshold for overriding parental decisions is successful in demonstrating that the harm threshold, like the best interests standard, suffers from the problem of indeterminacy. However, his focus on critiquing empirical rather than normative arguments for the harm threshold means that his broad conclusion that it is 'ill-judged' is not justified. Advocates of the harm threshold can accept that the concept of harm to a child is indeterminate, yet still invoke strong normative arguments for this way of responding to parental decisions that conflict with medical recommendations. I suggest that Birchley's discussion, rather than showing that the harm threshold is mistaken, instead highlights the importance of developing a comprehensive account of children's interests, for proponents of a best interests approach and for advocates of the harm threshold. PMID- 26553000 TI - Does acromegaly suffice to explain the origin of Pulcinella? A novel interpretation. PMID- 26553001 TI - Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence. AB - OBJECTIVE: Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. METHODS: PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta analysis was not conducted because of between-study heterogeneity. RESULTS: Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. CONCLUSION: Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. PMID- 26553002 TI - A comprehensive mRNA expression analysis of developing chicken articular cartilage. AB - Articular cartilage present at the ends of appendicular skeletal elements provides friction-less movement to the synovial joints and any damage to this tissue can lead to a degenerative disease of joint called osteoarthritis. During past two decades although many genes e.g.,Gdf5, Wnt9a, Noggin etc. have been identified and characterized in joint development, still a comprehensive understanding of molecular network(s) operational in articular cartilage morphogenesis is far from being drawn. Here we report identification of 36 genes (19 from literature survey and 17 from microarray analysis) that are expressed in developing chicken phalangeal joints in a spatiotemporally dynamic manner. For both these set of genes across the time window investigated we observed three kinds of expression patterns: early, late and constant. The early expressed genes are invariably expressed in a domain broader than the interzone while the late expressed genes are expressed in restricted spatial domains. The comprehensive expression analysis presented in this report provides a candidate list of molecular players involved in articular cartilage differentiation and/or maintenance. PMID- 26553003 TI - Reconstruction of 3D genome architecture via a two-stage algorithm. AB - BACKGROUND: The three-dimensional (3D) configuration of chromosomes within the eukaryote nucleus is an important factor for several cellular functions, including gene expression regulation, and has also been linked with cancer causing translocation events. While visualization of such architecture remains limited to low resolutions, the ability to infer structures at increasing resolutions has been enabled by recently-devised chromosome conformation capture techniques. In particular, when coupled with next generation sequencing, such methods yield an inventory of genome-wide chromatin contacts or interactions. Various algorithms have been advanced to operate on such contact data to produce reconstructed 3D configurations. Studies have shown that these reconstructions can provide added value over raw interaction data with respect to downstream biological insights. However, only limited, low-resolution reconstructions have been realized for mammals due to computational bottlenecks. RESULTS: Here we propose a two-stage algorithm to partially overcome these computational barriers. The central idea is to initially utilize existing reconstruction techniques on an individual chromosome basis, using intra-chromosomal contacts, and then to relatively position these chromosome-level reconstructions using inter chromosomal contacts. This two-stage strategy represents a natural approach in view of the within- versus between- chromosome distribution of contacts. It can increase resolution ~ 20 fold for mouse and human. After describing the algorithm we present 3D architectures for mouse embryonic stem cells and human lymphoblastoid cells. We evaluate the impact of several factors on reconstruction reproducibility and explore a variety of sampling schemes. We further analyze replicate data at differing resolutions obtained from recently devised in situ Hi C assays. In all instances we demonstrate insensitivity of the whole-genome 3D reconstruction obtained by the two-stage algorithm to the sampling strategy used. CONCLUSIONS: Our two-stage algorithm has the potential to significantly increase the resolution of 3D genome reconstructions. The improvements are such that we can progress from 1 Mb resolution to 100 kb resolution, notable since this latter value has been identified as critical to inferring topological domains in analyses performed on the contact (rather than 3D) level. PMID- 26553004 TI - Infrastructural challenges to better health in maternity facilities in rural Kenya: community and healthworker perceptions. AB - BACKGROUND: The efforts and commitments to accelerate progress towards the Millennium Development Goals for maternal and newborn health (MDGs 4 and 5) in low and middle income countries have focused primarily on providing key medical interventions at maternity facilities to save the lives of women at the time of childbirth, as well as their babies. However, in most rural communities in sub Saharan, access to maternal and newborn care services is still limited and even where services are available they often lack the infrastructural prerequisites to function at the very basic level in providing essential routine health care services, let alone emergency care. Lists of essential interventions for normal and complicated childbirth, do not take into account these prerequisites, thus the needs of most health facilities in rural communities are ignored, although there is enough evidence that maternal and newborn deaths continue to remain unacceptably high in these areas. METHODS: This study uses data gathered through qualitative interviews in Kitonyoni and Mwania sub-locations of Makueni County in Eastern Kenya to understand community and provider perceptions of the obstacles faced in providing and accessing maternal and newborn care at health facilities in their localities. RESULTS: The study finds that the community perceives various challenges, most of which are infrastructural, including lack of electricity, water and poor roads that adversely impact the provision and access to essential life-saving maternal and newborn care services in the two sub locations. CONCLUSIONS: The findings and recommendations from this study are important for the attention of policy makers and programme managers in order to improve the state of lower-tier health facilities serving rural communities and to strengthen infrastructure with the aim of making basic routine and emergency obstetric and newborn care services more accessible. PMID- 26553005 TI - Modulation of expression of heat shock proteins and apoptosis by Flueggea leucopyrus (Willd) decoction in three breast cancer phenotypes. AB - BACKGROUND: During the past few years, there has been an increasing interest among the Traditional and Folk medical practitioners of Sri Lanka in the use of a decoction prepared from Flueggea leucopyrus (Willd.) for treating various cancers including breast cancer. In the present study, the cytotoxicity of this decoction and its effects on Heat Shock Protein (HSP) expression and apoptosis were compared in three breast cancer phenotypes, to scientifically evaluate if a decoction prepared from F. leucopyrus (Willd.) is useful for the treatment of breast cancer. METHODS: Cytotoxic potential of the F. leucopyrus decoction was determined by evaluating its effects in MCF-7, MDA-MB-231 and SKBR-3 breast cancer cell lines, and MCF-10A (non-cancerous) breast cell line, by use of the Sulphorhodamine (SRB) assay. The effect of the decoction on HSP gene expression in the above cells was evaluated by (a) Real time reverse transcription PCR (RT PCR) and (b) Immunofluorescence analysis of HSP protein expression. Effects of the decoction on apoptosis were evaluated by (a) fluorescent microscopic examination of apoptosis related morphological changes and (b) DNA fragmentation (c) Caspase 3/7 assay. RESULTS: F. leucopyrus decoction can mediate significant cytotoxic effects in all three breast cancer cells phenotypes (IC50 values: 27.89, 99.43, 121.43 MUg/mL at 24 h post incubation periods, for MCF-7, MDA-MB 231, SKBR-3 respectively) with little effect in the non-cancerous breast cell line MCF-10A (IC50: 570.4 MUg/mL). Significant (*P <0.05) inhibitions of HSP 90 and HSP 70 expression were mediated by the decoction in MCF-7 and MDA-MB-231, with little effect in the SKBR-3 cells. Clear apoptotic morphological changes on Acridine orange/Ethidium bromide staining and DNA fragmentation were observed in all three breast cancer cell lines. Caspase 3/7 were significantly (*P <0.05) activated only in MDA-MB-231 and SKBR-3 cells indicating caspase dependent apoptosis in these cells and caspase independent apoptosis in MCF-7 cells. CONCLUSIONS: Modulation of HSP 90 and HSP 70 expressions is a possible mechanism by which the decoction of F. leucopyrus mediates cytotoxic effects MCF-7 and MDA MB-231 cells. This effect appears to correlate with enhanced apoptosis in these cells. In SKBR-3 cells, mechanisms other than HSP inhibition may be utilized to a greater extent by the decoction to mediate the observed cytotoxic effects. Overall findings suggest that the decoction has the potential to be exploited further for effective treatment of breast cancer. PMID- 26553006 TI - Effect of phytosterols and inulin-enriched soymilk on LDL-cholesterol in Thai subjects: a double-blinded randomized controlled trial. AB - BACKGROUND: Hypercholesterolemia, particularly high LDL-c and non-HDL-c levels, is a traditional risk for cardiovascular disease. Ingestion of diets containing phytosterols and inulin can reduce plasma LDL-c and triglyceride levels, respectively. Phytosterols and inulin-enriched soymilk may be an alternative for a supplemental diet to improve both LDL-c and non-HDL-c to reduce the risk of cardiovascular disease. METHODS: Two hundred and forty subjects who were 18 years old or older and had a baseline LDL-c of 130 mg/dl or higher were enrolled into the double-blinded randomized controlled trial study. Subjects were randomly assigned into the study group that received 2 g/day of phytosterols and 10 g/day of inulin-enriched soymilk or into the control group that received standard soymilk. The lipid profile was measured every 2 weeks for 8 weeks. Primary outcomes were 1) to determine the LDL-c reduction after consumption of phytosterols and inulin-enriched soymilk for 8 weeks and 2) to compare the difference of the LDL-c levels between the study and control groups. The secondary outcomes were to compare the difference of TC, TG and HDL-c between the study and control groups. RESULTS: At the end of the study, the median LDL-c levels decreased significantly from 165 (132, 254) mg/dl to 150 (105, 263) mg/dl in the study group (p < 0.001) and from 165 (130, 243) mg/dl to 159 (89, 277) mg/dl in the control group (p = 0.014). The LDL-c reduction was significantly better in the study group (-10.03%, (-37.07, 36.00) vs -1.31% (-53.40, 89.73), p < 0.001). TC also reduced significantly by 6.60% in the study group while it reduced only by 1.76% in the control group (p < 0.001). There were no statistical differences in TG and HDL-c levels between both study groups. The adverse events in the study group and the control groups were not different (RR 1.33 [0.871 2.030, 95 % CI]). CONCLUSION: Daily consumption of soymilk containing 2 g of phytosterols and 10 g of inulin reduced TC and LDL-c better than standard soymilk. It had no effect on TG and HDL-c levels compared to standard soymilk. Both soymilk products were comparably safe. TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20150417001 date: April 17, 2015. PMID- 26553008 TI - Study of surface charges in ballistic deflection transistors. AB - This paper presents a comprehensive study of the behavior of surface charges in ballistic deflection transistors, at room temperature, where the in-plane geometry associating two drains with two gates in push-pull modes allows the control of electron path. Monte Carlo simulations were performed and compared with experimental data by using different models for accounting for surface charge effects. The simple model which assumes a constant and uniform value of the surface charge provides good results at equilibrium, but it is not able to correctly reproduce the BDT's complex behavior when biased. We have confirmed that for a correct description of the device operation it is necessary to use a model allowing the surface charge to adapt itself locally to the carrier concentration in its surroundings. PMID- 26553009 TI - Editorial: Supramolecular Systems in Nanomedicines: Therapeutic Applications and Future Perspectives - Part I. PMID- 26553007 TI - G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy. AB - BACKGROUND: Evidence-based guidelines concerning the older head and neck cancer (HNCA) patient are lacking. Accurate patient selection for optimal care management is therefore challenging. We examined if geriatric assessment is indicative of long-term health-related quality of life (HRQOL) and overall survival in this unique population. METHODS: All HNCA patients, aged >=65 years, eligible for curative radio(chemo)therapy were evaluated with the Geriatric-8 (G 8) questionnaire and a comprehensive geriatric assessment (CGA). Euroqol-5 dimensions (EQ-5D) and survival were collected until 36 months post treatment start. Repeated measures ANOVA was applied to analyse HRQOL evolution in 'fit' and 'vulnerable' patients, defined by G-8. Kaplan-Meier curves and cox proportional hazard analysis were established for determination of the prognostic value of geriatric assessments. Quality-adjusted survival was calculated in both patient subgroups. RESULTS: One hundred patients were recruited. Seventy-two percent of patients were considered vulnerable according to CGA (>=2 abnormal tests). Fit patients maintained a relatively acceptable long-term HRQOL, whilst vulnerable patients showed significantly lower median health states. The difference remained apparent at 36 months. Vulnerability, as classified by G-8 or CGA, came forward as independent predictor for lower EQ-5D index scores. After consideration of confounders, a significantly lower survival was observed in patients defined vulnerable according to G-8, compared to fit patients. A similar trend was seen based on CGA. Calculation of quality-adjusted survival showed significantly less remaining life months in perfect health in vulnerable patients, compared to fit ones. CONCLUSIONS: G-8 is indicative of quality adjusted survival, and should be considered at time of treatment decisions for the older HNCA patient. PMID- 26553010 TI - Proline Oxidase (POX) as A Target for Cancer Therapy. AB - Proline dehydrogenase/proline oxidase (PRODH/POX) is an enzyme catalyzing the first step of proline degradation, during which ROS and/or ATP is generated. POX is widely distributed in living organisms and is responsible for a number of regulatory processes such as redox homeostasis, osmotic adaptation, cell signaling and oxidative stress. Recent data provided evidence that POX plays an important role in carcinogenesis and tumor growth. POX may induce apoptosis in both intrinsic and extrinsic way. Due to ROS generation, POX may induce caspase-9 activity, which mediates mitochondrial apoptosis (intrinsic apoptosis pathway). POX can also stimulate TRAIL (tumor necrosis factorrelated apoptosis inducing ligand) and DR5 (death receptor 5) expression, resulting in cleavage of procaspase-8 and thus extrinsic apoptotic pathway. However, this tumor suppressor in certain environmental conditions may act as a prosurvival factor. Genotoxic, inflammatory and metabolic stress may switch POX from tumor growth inhibiting to tumor growth supporting factor. The potential mechanisms which may regulate switching of POX mode are discussed in this review. PMID- 26553011 TI - Increased Prevalence of Controlled Viremia and Decreased Rates of HIV Drug Resistance Among HIV-Positive People Who Use Illicit Drugs During a Community wide Treatment-as-Prevention Initiative. AB - BACKGROUND: Although treatment-as prevention (TasP) is a new cornerstone of global human immunodeficiency virus (HIV)-AIDS strategies, its effect among HIV positive people who use illicit drugs (PWUD) has yet to be evaluated. We sought to describe longitudinal trends in exposure to antiretroviral therapy (ART), plasma HIV-1 RNA viral load (VL) and HIV drug resistance during a community-wide TasP intervention. METHODS: We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services study, a prospective cohort of HIV-positive PWUD linked to HIV clinical monitoring records. We estimated longitudinal changes in the proportion of individuals with VL <50 copies/mL and rates of HIV drug resistance using generalized estimating equations (GEE) and extended Cox models. RESULTS: Between 1 January 2006 and 30 June 2014, 819 individuals were recruited and contributed 1 or more VL observation. During that time, the proportion of individuals with nondetectable VL increased from 28% to 63% (P < .001). In a multivariable GEE model, later year of observation was independently and positively associated with greater likelihood of nondetectable VL (adjusted odds ratio = 1.20 per year; P < .001). Although the proportion of individuals on ART increased, the incidence of HIV drug resistance declined (adjusted hazard ratio = 0.78 per year; P = .011). CONCLUSIONS: We observed significant improvements in several measures of exposure to ART and virologic status, including declines in HIV drug resistance, in this large long-running community-recruited cohort of HIV seropositive illicit drug users during a community-wide ART expansion intervention. Our findings support continued efforts to scale up ART coverage among HIV-positive PWUD. PMID- 26553013 TI - Replication in Psychological Science. PMID- 26553012 TI - In Vivo Profiling and Distribution of Known and Novel Phase I and Phase II Metabolites of Efavirenz in Plasma, Urine, and Cerebrospinal Fluid. AB - Efavirenz (EFV) is principally metabolized by CYP2B6 to 8-hydroxy-efavirenz (8OH EFV) and to a lesser extent by CYP2A6 to 7-hydroxy-efavirenz (7OH-EFV). So far, most metabolite profile analyses have been restricted to 8OH-EFV, 7OH-EFV, and EFV-N-glucuronide, even though these metabolites represent a minor percentage of EFV metabolites present in vivo. We have performed a quantitative phase I and II metabolite profile analysis by tandem mass spectrometry of plasma, cerebrospinal fluid (CSF), and urine samples in 71 human immunodeficiency virus patients taking efavirenz, prior to and after enzymatic (glucuronidase and sulfatase) hydrolysis. We have shown that phase II metabolites constitute the major part of the known circulating efavirenz species in humans. The 8OH-EFV-glucuronide (gln) and 8OH EFV-sulfate (identified for the first time) in humans were found to be 64- and 7 fold higher than the parent 8OH-EFV, respectively. In individuals (n = 67) genotyped for CYP2B6, 2A6, and CYP3A metabolic pathways, 8OH-EFV/EFV ratios in plasma were an index of CYP2B6 phenotypic activity (P < 0.0001), which was also reflected by phase II metabolites 8OH-EFV-glucuronide/EFV and 8OH-EFV-sulfate/EFV ratios. Neither EFV nor 8OH-EFV, nor any other considered metabolites in plasma were associated with an increased risk of central nervous system (CNS) toxicity. In CSF, 8OH-EFV levels were not influenced by CYP2B6 genotypes and did not predict CNS toxicity. The phase II metabolites 8OH-EFV-gln, 8OH-EFV-sulfate, and 7OH-EFV-gln were present in CSF at 2- to 9-fold higher concentrations than 8OH EFV. The potential contribution of known and previously unreported EFV metabolites in CSF to the neuropsychological effects of efavirenz needs to be further examined in larger cohort studies. PMID- 26553014 TI - Memory Transmission in Small Groups and Large Networks: An Agent-Based Model. AB - The spread of social influence in large social networks has long been an interest of social scientists. In the domain of memory, collaborative memory experiments have illuminated cognitive mechanisms that allow information to be transmitted between interacting individuals, but these experiments have focused on small scale social contexts. In the current study, we took a computational approach, circumventing the practical constraints of laboratory paradigms and providing novel results at scales unreachable by laboratory methodologies. Our model embodied theoretical knowledge derived from small-group experiments and replicated foundational results regarding collaborative inhibition and memory convergence in small groups. Ultimately, we investigated large-scale, realistic social networks and found that agents are influenced by the agents with which they interact, but we also found that agents are influenced by nonneighbors (i.e., the neighbors of their neighbors). The similarity between these results and the reports of behavioral transmission in large networks offers a major theoretical insight by linking behavioral transmission to the spread of information. PMID- 26553016 TI - Is there benefit in extensive screening for cancer in patients with unprovoked venous thromboembolism? PMID- 26553015 TI - A bulk segregant transcriptome analysis reveals metabolic and cellular processes associated with Orange allelic variation and fruit beta-carotene accumulation in melon fruit. AB - BACKGROUND: Melon fruit flesh color is primarily controlled by the "golden" single nucleotide polymorhism of the "Orange" gene, CmOr, which dominantly triggers the accumulation of the pro-vitamin A molecule, beta-carotene, in the fruit mesocarp. The mechanism by which CmOr operates is not fully understood. To identify cellular and metabolic processes associated with CmOr allelic variation, we compared the transcriptome of bulks of developing fruit of homozygous orange and green fruited F3 families derived from a cross between orange and green fruited parental lines. RESULTS: Pooling together F3 families that share same fruit flesh color and thus the same CmOr allelic variation, normalized traits unrelated to CmOr allelic variation. RNA sequencing analysis of these bulks enabled the identification of differentially expressed genes. These genes were clustered into functional groups. The relatively enriched functional groups were those involved in photosynthesis, RNA and protein regulation, and response to stress. CONCLUSIONS: The differentially expressed genes and the enriched processes identified here by bulk segregant RNA sequencing analysis are likely part of the regulatory network of CmOr. Our study demonstrates the resolution power of bulk segregant RNA sequencing in identifying genes related to commercially important traits and provides a useful tool for better understanding the mode of action of CmOr gene in the mediation of carotenoid accumulation. PMID- 26553017 TI - N2 extenuates experimental ischemic stroke through platelet aggregation inhibition. AB - INTRODUCTION: Thromboxane A2 (TXA2) can induce the platelet aggregation and lead to thrombosis. This will cause the low-reflow phenomenon after ischemic stroke and aggravate the damage of brain issues. Therefore, it is potential to develop the drugs inhibiting TXA2 pathway to treat cerebral ischemia. AIM: This study aims to prove the protective effect of N2 (4-(2-(1H-imidazol-1-yl) ethoxy)-3 methoxybenzoic acid) on focal cerebral ischemia and reperfusion injury through platelet aggregation inhibition. MATERIALS AND METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) is used as the animal model. Neurological deficit score, Morris water maze, postural reflex test, Limb-use asymmetry test, infarct volume, and water content were performed to evaluate the protective effect of N2 in MCAO/R rats. 9, 11-dieoxy-11alpha, 9alpha-methanoepoxyprostaglandin F2alpha (U46619) or adenosine diphosphate (ADP) was used as the inducer of platelet aggregation. RESULTS AND CONCLUSIONS: N2 can improve the motor function, learning and memory ability in MCAO/R rats while reducing the infarct volume. N2 can inhibit TXA2 formation but promote PGI2, and can inhibit platelet aggregation induced by U46619 and ADP. Further, N2 inhibits thrombosis with a minor adverse effect of bleeding than Clopidogrel. In conclusion, N2 can produce the protective effect on MCAO/R brain injury through inhibiting TXA2 formation, platelet aggregation and thrombosis. PMID- 26553018 TI - Role of blood transfusion product type and amount in deep vein thrombosis after cardiac surgery. AB - BACKGROUND: Postoperative deep vein thrombosis (DVT) is associated with significant morbidity. Even with maximal thromboprophylaxis, postoperative DVT is present in 10% of cardiac surgery patients, and is linked to receiving transfusion. We hypothesized that the incidence of DVT varies with the transfused blood product type, and increases with transfusion dose. STUDY DESIGN AND METHODS: 139/1070 cardiac surgery patients have DVT despite maximal chemo and mechanical prophylaxis. DVTs were detected via serial perioperative duplex venous scans (DVS). Red blood cells (RBC), platelets (PLT), plasma (FFP) and cryoprecipitate transfusion data were collected. RESULTS: Transfusion was used in 506(47%) patients: RBC [468(44%); 4.0 +/- 4.2u]; FFP [155(14.5%); 3.5 +/- 2.3 u]; PLT [185(17.3%); 2.2 +/- 1.3 u] and Cryoprecipitate [51(4.8%); 1.3 +/- 0.6 u]. Isolated RBC transfusion accounted for 92.6% patients receiving one product, and their DVT rate was increased considerably compared to no transfusion (16.7% versus 7.3%; P<0.001). Incidence of DVT increased substantially for multiple product transfusions; particularly when both RBC and FFP are used (25%-40%). Relative to no RBC (n=602), multivariate logistic regression analysis identified a significant RBC-DVT dose dependent relation (P<0.001) with: 1-3 RBC units [n=285, AOR=1.95(1.23-3.07), adjusted odds ratio (95% confidence interval)]; 4-6 units [n=117; AOR=1.65(0.86-3.20)]; and >= 7 RBC units [n=66; 3.19(1.52-6.70)]. This relation also increased according to an RBC*FFP interaction term [AOR=1.87(1.11-3.22); P=0.022]. CONCLUSION: RBC transfusion is associated with increased risk of DVT after cardiac surgery in a dose-dependent fashion that is exacerbated when accompanied with FFP. Postoperative screening diagnostic DVS are warranted in this transfused, high risk for DVT population to facilitate timely therapeutic intervention. PMID- 26553019 TI - Prevention and follow-up in thromboembolic ischemic stroke: Do we need to think out of the box? AB - Stroke is one of the most debilitating thrombotic diseases, and world-wide it is estimated that by, 2030, 23 million people will be affected. Except for the impact on the individual families, the world economy is also affected adversely. Although the medical treatment and knowledge of stroke are both increasing and well-researched, we still do not see a decrease in stroke prevalence. Currently various diagnostic tests are employed to determine the specific type of ischemic stroke as classified by the TOAST criteria. However, these tests are done after the stroke has occurred and therefore only contribute to the unquestionably crucial aspect of treating that particular stroke patient, but it does not improve prevention of future events. Prevention strategies regarding first-time stroke need urgent attention given the alarming present and future incidence of stroke. Therefore, here we discuss the importance of stroke prevention and suggest a more inclusive, perhaps "new" comprehensive approach for pre-stroke screening. Ultrastructural tests, particularly scanning electron microscopy, provide an innovative and novel advance in preventative and individualized patient-centered precision medicine. This precise technique when used in combination with well-established methods, as well as viscoelastic methods like thromboelastography (TEG), as a screening tool to prevent stroke can ultimately alleviate the financial and economical burden of stroke and also improve quality of life. Although we appreciate the fact that this suggestion might be difficult to accept by clinicians, a bold new approach is needed to address this pandemic we call stroke. PMID- 26553020 TI - Identifying venous thromboembolism and major bleeding in emergency room discharges using administrative data. AB - BACKGROUND: Administrative data can be used to identify venous thromboembolism (VTE) and major bleeding (MB) events. However, the validity of this data in emergency room discharge records in Canada is unknown. METHODS: We conducted a single-institution retrospective chart re-abstraction study in London, Canada. We identified all adult patients with a VTE or MB code included in the mandatory Canadian Institute for Health Information National Ambulatory Care Reporting System seen at our institution between July 2002 and March 2014. VTE was defined using the International Classification of Diseases, 10th revision (ICD-10CM) codes for deep venous thrombosis (DVT), and pulmonary embolism (PE) whereas MB was defined using codes for intracerebral hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, upper, and lower gastrointestinal bleeding. A random sample of 50 patients was obtained for each condition. Two abstractors independently conducted blinded diagnostic adjudication using standard criteria. Agreement was calculated using kappa statistics. Positive predictive values were calculated for VTE, MB and each diagnosis. RESULTS: Overall, ICD-10CM codes demonstrated very good ability to identify major bleeding events (PPV 88%). Diagnostic codes performed particularly well for all intracranial and lower gastrointestinal bleeds. In contrast, ICD-10CM codes for VTE had moderate ability (PPV 49%). Diagnostic codes for PE performed better than those for DVT. CONCLUSION: Single ICD-10CM codes for venous thromboembolism have moderate predictive value for identifying DVT and PE in emergency room discharges. In contrast, codes for MB events have very good ability and it would be adequate to use them for research purposes. PMID- 26553021 TI - Quality of HbA1c Measurement in Trinidad and Tobago. AB - BACKGROUND: Monitoring of HbA1c is the standard of care to assess diabetes control. In Trinidad & Tobago (T&T) there are no existing data on the quality of HbA1c measurement. Our study examined the precision and accuracy of HbA1c testing in T&T. METHODS: Sets of 10 samples containing blinded duplicates were shipped to laboratories in T&T. This exercise was repeated 6 months later. Precision and accuracy were estimated for each laboratory/method. RESULTS: T&T methods included immunoassay, capillary electrophoresis, and boronate affinity binding. Most, but not all, laboratories demonstrated acceptable precision and accuracy. CONCLUSIONS: Continuous oversight of HbA1c testing (eg, through proficiency testing) in T&T is recommended. These results highlight the lack of oversight of HbA1c testing in some developing countries. PMID- 26553022 TI - Evaluation of System Accuracy of the GlucoMen LX Plus Blood Glucose Monitoring System With Reference to ISO 15197:2013. PMID- 26553023 TI - Hemoglobin A1c and Self-Monitored Average Glucose: Validation of the Dynamical Tracking eA1c Algorithm in Type 1 Diabetes. AB - BACKGROUND: Previously we have introduced the eA1c-a new approach to real-time tracking of average glycemia and estimation of HbA1c from infrequent self monitoring (SMBG) data, which was developed and tested in type 2 diabetes. We now test eA1c in type 1 diabetes and assess its relationship to the hemoglobin glycation index (HGI)-an established predictor of complications and treatment effect. METHODS: Reanalysis of previously published 12-month data from 120 patients with type 1 diabetes, age 39.15 (14.35) years, 51/69 males/females, baseline HbA1c = 7.99% (1.48), duration of diabetes 20.28 (12.92) years, number SMBG/day = 4.69 (1.84). Surrogate fasting BG and 7-point daily profiles were derived from these unstructured SMBG data and the previously reported eA1c method was applied without any changes. Following the literature, we calculated HGI = HbA1c - (0.009 * Fasting BG + 6.8). RESULTS: The correlation of eA1c with reference HbA1c was r = .75, and its deviation from reference was MARD = 7.98%; 95% of all eA1c values fell within +/-20% from reference. The HGI was well approximated by a linear combination of the eA1c calibration factors: HGI = 0.007552*theta1 + 0.007645*theta2 - 3.154 (P < .0001); 73% of low versus moderate high HGIs were correctly classified by the same factors as well. CONCLUSIONS: The eA1c procedure developed in type 2 diabetes to track in real-time changes in average glycemia and present the results in HbA1c-equivalent units has shown similar performance in type 1 diabetes. The eA1c calibration factors are highly predictive of the HGI, thereby explaining partially the biological variation causing discrepancies between HbA1c and its linear estimates from SMBG data. PMID- 26553024 TI - Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo. AB - BACKGROUND: Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system. RESULTS: Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice with/without pups. The resultant networks were very robust and assembled about structural hubs, with evidence that interleukin (IL)-12 (p40), IL 13 and monocyte chemoattractant protein (MCP)-1 were the primary drivers of network behavior. Network structural conservation across physiological scenarios coupled with the successful empirical validation of our approach suggested that in silico network perturbations can predict in vivo qualitative responses. In silico perturbation of network components also captured biological features of cytokine interactions (antagonism, synergy, redundancy). CONCLUSION: These findings highlight the potential of network-based approaches in identifying novel cytokine pharmacological targets and in predicting the effects of their exogenous manipulation in inflammatory/immune disorders. PMID- 26553025 TI - Macrolide Use and Neutrophil Function/Cytokine Levels in Hospitalized Patients with Community-Acquired Pneumonia: A Pilot Study. AB - PURPOSE: The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use--a known modulator of inflammatory response. METHODS: Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2-4 and 5-7, depending on a patient's length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide. RESULTS: A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-gamma levels, and favorable clinical outcomes were present in the macrolide group. CONCLUSIONS: This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted. PMID- 26553026 TI - A novel ethanol-tolerant laccase, Tvlac, from Trametes versicolor. AB - OBJECTIVES: To produce and characterize novel laccases with ethanol tolerance from Trametes versicolor using agriculture by-products as energy source. RESULTS: Trametes versicolor 1017 produces two laccase isoenzymes with a total activity of 10 U ml(-1) within 8 days when using wheat bran and peanut powder as energy sources in liquid culture medium. A novel isoenzyme, named Tvlac, was identified, purified and characterized. Its optimum pH and temperature were from 4.5 to 5 and 55 to 60 degrees C, respectively. Its activity was stimulated by ethanol at 10 % (v/v) which increased the V 0. CONCLUSIONS: The biochemical properties of Tvlac substantiate the potential of this enzyme for applications under an aqueous ethanol mixture environment. PMID- 26553027 TI - Nitrogen- Doped Graphene Quantum Dots: "Turn-off" Fluorescent Probe for Detection of Ag(+) Ions. AB - Highly luminescent nitrogen-doped graphene quantum dots (N-GQDs) were prepared from glucose and ammonia as carbon and nitrogen sources, respectively. The N-GQDs showed a strong emission at 458 nm with excitation at 360 nm. The N-GQDs exhibited analytical potential as sensing probes for silver ions determination. Factors affecting the fluorescence sensing of Ag(+) ions such as pH, N-GQDs concentration and incubation time were studied using Box-Behnken experimental design. The optimum conditions were determined as pH 7, N-GQDs concentration 1 mg/mL and time 60 min. It suggested that N-GQDs exhibited high sensitivity and selectivity toward Ag(+). The linear range of N-GQDs and the limit of detection (LOD) were 0.2-40 MUM and 168 nM, respectively. The N-GQDs-based Ag(+) ions sensor was successfully applied to the determination of Ag(+) in tap water and real river water samples. PMID- 26553028 TI - Interaction of Graphene Quantum Dots with 4-Acetamido-2,2,6,6 Tetramethylpiperidine-Oxyl Free Radicals: A Spectroscopic and Fluorimetric Study. AB - We report on the interaction of graphene quantum dots (GQDs) with 4-acetamido 2,2,6,6-tetramethylpiperidine-oxyl (4-acetamido-TEMPO) free radicals. The GQDs were N and S, N doped. The fluorescence quantum yields were higher for the doped GQDs compared to the undoped. The interaction is assessed by spectrofluorimetric, steady state/time resolved fluorescence and electron paramagnetic resonance (EPR) techniques. Fluorescence quenching was observed upon the addition of 4-acetamido TEMPO to the GQDs. Photo-induced electron transfer (PET) mechanism was suggested as the plausible mechanism involved in the fluorescence quenching in which 4 acetamido-TEMPO acted as the electron acceptor. PMID- 26553029 TI - Effects of refractive errors on visual evoked magnetic fields. AB - BACKGROUND: The latency and amplitude of visual evoked cortical responses are known to be affected by refractive states, suggesting that they may be used as an objective index of refractive errors. In order to establish an easy and reliable method for this purpose, we herein examined the effects of refractive errors on visual evoked magnetic fields (VEFs). METHODS: Binocular VEFs following the presentation of a simple grating of 0.16 cd/m(2) in the lower visual field were recorded in 12 healthy volunteers and compared among four refractive states: 0D, +1D, +2D, and +4D, by using plus lenses. RESULTS: The low-luminance visual stimulus evoked a main MEG response at approximately 120 ms (M100) that reversed its polarity between the upper and lower visual field stimulations and originated from the occipital midline area. When refractive errors were induced by plus lenses, the latency of M100 increased, while its amplitude decreased with an increase in power of the lens. Differences from the control condition (+0D) were significant for all three lenses examined. The results of dipole analyses showed that evoked fields for the control (+0D) condition were explainable by one dipole in the primary visual cortex (V1), while other sources, presumably in V3 or V6, slightly contributed to shape M100 for the +2D or +4D condition. CONCLUSIONS: The present results showed that the latency and amplitude of M100 are both useful indicators for assessing refractive states. The contribution of neural sources other than V1 to M100 was modest under the 0D and +1D conditions. By considering the nature of the activity of M100 including its high sensitivity to a spatial frequency and lower visual field dominance, a simple low-luminance grating stimulus at an optimal spatial frequency in the lower visual field appears appropriate for obtaining data on high S/N ratios and reducing the load on subjects. PMID- 26553030 TI - Association between patient-provider communication and lung cancer stigma. AB - PURPOSE: The majority (95 %) of lung cancer patients report stigma, with 48 % of lung cancer patients specifically reporting feeling stigmatized by their medical providers. Typically associated with the causal link to smoking and the historically poor prognosis, lung cancer stigma can be seen as a risk factor for poor psychosocial and medical outcomes in the context of lung cancer diagnosis and treatment. Thus, modifiable targets for lung cancer stigma-reducing interventions are needed. The present study sought to test the hypothesis that good patient-provider communication is associated with lower levels of lung cancer stigma. METHODS: Lung cancer patients (n = 231) across varying stages of disease participated in a cross-sectional, multisite study designed to understand lung cancer stigma. Patients completed several survey measures, including demographic and clinical characteristics, a measure of patient-provider communication (Consumer Assessment of Healthcare Providers and Systems Program or CAHPS), and a measure of lung cancer stigma (Cataldo Lung Cancer Stigma Scale). RESULTS: As hypothesized, results indicated that good patient-provider communication was associated with lower levels of lung cancer stigma (r = -0.18, p < 0.05). These results remained significant, even when controlling for relevant demographic and clinical characteristics (Stan. beta = -0.15, p < 0.05). CONCLUSIONS: Results indicate that good patient-provider communication is associated with lower levels of lung cancer stigma, suggesting that improving patient-provider communication may be a good intervention target for reducing lung cancer stigma. PMID- 26553031 TI - Prediction of critical weight loss during radiation treatment in head and neck cancer patients is dependent on BMI. AB - PURPOSE: The aims of the present study were to explore pre-treatment predictors of weight loss during radiation treatment only in head and neck cancer (HNSCC) patients and investigate the weight loss in patients with or without a feeding tube. METHODS: Retrospectively, weight change during curative radiotherapy was investigated in 476 consecutive HNSCC patients. Independent predictors were identified using multivariate regression analysis with weight loss below or above 5 % as the primary dependent variable. RESULTS: Baseline BMI, tumor site, and stage predicted weight loss above 5 %. The odds of weight loss above 5 % in patients with BMI >25 were 3.00 +/- 0.64 times higher compared with patients with BMI <25 (p < 0.0001). Patients with pharyngeal, oral cavity, or supraglottic tumors had 3.12 +/- 0.80 times higher odds of weight loss above 5 % compared with glottic cancer patients (p < 0.0001), and the odds were 1.68 +/- 0.40 times higher in stage III-IV patients compared with stage I-II patients (p = 0.03). Seperate analyses revealed that tumor site and stage only predicted weight loss in patients with BMI >25 but not in patients with BMI <25. Patients receiving a feeding tube weighed less than patients without (73.8 vs 78.3 kg) and feeding tube reduced, but did not prevent, weight loss which averaged 6.7 +/- 4.7 kg (7.4 +/- 4.7 %) compared with 4.7 +/- 5.9 kg (5.5 +/- 6.0 %) in patients without a feeding tube (P < 0.0001). CONCLUSION: Pre-treatment BMI, tumor site and stage predicted weight loss above 5 % in HNSCC patients during radiotherapy. BMI should be considered when analyzing weight loss in HNSCC patients receiving curative radiotherapy. PMID- 26553032 TI - Outpatient management of intensively treated acute leukemia patients--the patients' perspective. AB - PURPOSE: In recent years, patients with acute leukemia (AL) have, to a greater extent, been managed in an outpatient setting where they live at home but appear every other day for follow-up visits at hospital. This qualitative article elucidates how patients with AL experience the different conditions of the inpatient and outpatient settings and how they reflect on these transitions in order to create meaning in and keep up everyday life. METHODS: Qualitative semi structured individual interviews twice with each AL patient focusing on the outpatient setting, impact on everyday life, responsibility and the home were performed. Twenty-two patients were interviewed the first time, and 15 of these were interviewed the second time. The data were analyzed in an everyday life relational perspective. RESULTS: Outpatient management facilitates time to be administrated by the patients and thereby the possibility of maintaining everyday life, which was essential to the patients. The privacy ensured by the home was important to patients, and they accepted the necessary responsibility that came with it. However, time spent together with fellow patients and their relatives was an important and highly valued part of their social life. CONCLUSIONS: Approached from the patient perspective, outpatient management provided a motivation for patients as it ensured their presence at home and provided the possibility of taking part in everyday life of the family, despite severe illness and intensive treatment. This may suggest a potential for extending the outpatient management further and also for patient involvement in own care. PMID- 26553033 TI - Weekly carboplatin in combination with weekly paclitaxel in the treatment of metastatic non-small cell lung cancer: a single center 10-year experience. AB - PURPOSE: The primary objective of this retrospective analysis is to assess efficacy and toxicity of a chemotherapeutic regimen using weekly carboplatin in combination with weekly paclitaxel as first-line therapy for advanced/metastatic non-small cell lung cancer (NSCLC). METHODS: All patients with stage IIIB/IV NSCLC treated with weekly carboplatin AUC (area under the curve) 3 days 1, 8, 15, q4w in combination with weekly paclitaxel 75 mg/m(2) days 1, 8, 15, q4w as first line therapy at the Kantonsspital Graubuenden between August 2004 and May 2014 were retrospectively analyzed by medical record review. RESULTS: A total of 90 patients were treated. Median age was 66 years (range 39-88). A total of 229 chemotherapy cycles were administered. Hematological and non-hematological toxicity were acceptable allowing for a median relative dose intensity for all planned treatment cycles of 76 %. Overall response rate was 34 %. Median overall and progression free survival was 6.3 (95 % CI, 4.9-8.7) and 3.4 (95 % CI, 2.3 5.1) months, respectively. Patients with an ECOG performance score (PS) of 0 or 1 had a significantly better OS compared to patients with a PS of >=2. No statistically significant difference was observed in patients younger or older than 70 years of age. CONCLUSIONS: Weekly carboplatin in combination with weekly paclitaxel results in good response rates and acceptable toxicity in patients with advanced and metastatic NSCLC including patients with poor risk features (brain metastases, older age, and impaired PS). Nonetheless, selecting the right patient for a platinum-based combination treatment remains an important task in clinical practice. PMID- 26553034 TI - Unenhanced Cone Beam Computed Tomography and Fusion Imaging in Direct Percutaneous Sac Injection for Treatment of Type II Endoleak: Technical Note. PMID- 26553035 TI - Acceptability of provider-initiated HIV testing as an intervention for prevention of mother to child transmission of HIV and associated factors among pregnant women attending at Public Health Facilities in Assosa town, Northwest Ethiopia. AB - BACKGROUND: Despite more efforts for prevention of mother to child HIV transmission, still there are problems with provider-initiated HIV testing. This study was done to assess the acceptance rate of provider-initiated HIV testing among antenatal care attendants and its associated factors. METHODS: Institutions based cross sectional study with a sample size of 398 was conducted from February to March 2014 in two health facilities in Assosa town. Proportional allocation of the sample size of health facilities followed by systematic sampling method was done; data were collected using an interviewer administered questionnaire. Bivariate and multivariate regression analysis was employed using SPSS version 20. RESULTS: A total of 386 pregnant women participated with response rate 97 % and 312 (80.8 %) of them accepted provider-initiated HIV testing. The odds of acceptance of provider-initiated HIV testing was higher among rural residents (AOR 4.04; 95 % CI 1.24-13.11) than urban. It was also higher among students (AOR 6.00; 95 % CI 1.45-24.75), merchants (AOR 4.43; 95 % CI 1.18-16.68) and employed women (AOR 2.15; 95 % CI 1.08-4.30) than housewives. Pregnant women who had no stigmatized attitude towards people living with HIV/AIDS were more likely to accept testing (AOR 3.54; 95 % CI 1.23-10.16) than who had a strong stigmatized attitude. In addition, those who planned to disclose their test results from their husbands were higher odd of acceptance (AOR 14.85; 95 % CI 4.60-47.94) than who secreted. CONCLUSION: Acceptance of provider-initiated HIV testing among pregnant women attending for antenatal care services was relatively high. Mothers from urban residence, occupational satus being housewives, stigmatization and not having a plan to disclose the status of test results were negatively affect the acceptance of provider-initiated HIV testing. During counselling sessions, antenatal care providers should focus on barriers of provider-initiated HIV testing such as residence, occupational status, stigmatized attitudes and disclosure status of results of HIV tests. PMID- 26553036 TI - Immunoglobulin G4-associated autoimmune hepatitis may be found in Western countries. AB - BACKGROUND: Immunoglobulin G4-related disease is a multi-systemic autoimmune disease. The sole involvement of the liver has been recently reported in Japanese patients and named "immunoglobulin G4-associated autoimmune hepatitis". AIM: To examine the baseline and the 2-year follow-up characteristics of non-Asian patients with immunoglobulin G4-associated autoimmune hepatitis compared to patients with classical autoimmune hepatitis. METHODS: This was a retrospective study of patients who had undergone liver biopsy between March 2009 and January 2012 before starting any treatment. All patients were treated according to the guidelines. Immunoglobulin G4-associated autoimmune hepatitis was diagnosed according to Umemura's histological definition: at least 10 positive immunoglobulin G4-plasma cells per high power field. RESULTS: Among 28 enrolled patients (males 39%, median age 54 years): 7 had immunoglobulin G4-associated autoimmune hepatitis (25%) and 21 had classical hepatitis; fibrosis and activity stages were F1: 57%, F2: 11%, F3: 11%, F4: 21% and A1: 18%, A2: 39%, A3: 43%. Alanine aminotransferase (ALT) activity and serum immunoglobulin G levels were similar in the two groups at baseline and at 2 years. Complete biochemical response (normal ALT) was similar in immunoglobulin G4-associated autoimmune hepatitis and classical hepatitis (67% vs. 59% at 2 years, p=0.74). CONCLUSION: Immunoglobulin G4-associated autoimmune hepatitis has been observed in Western patients and seems to evolve in a similar manner to classical hepatitis. PMID- 26553037 TI - Phenotypic Modulation and Neuroprotective Effects of Olfactory Ensheathing Cells: a Promising Tool for Cell Therapy. AB - Olfactory Ensheathing Cells (OECs), exhibiting phenotypic characteristics of both astrocytes and Schwann Cells, show peculiar plasticity. In vitro, OECs promote axonal growth, while in vivo they promote remyelination of damaged axons. We decided to further investigate OEC potential for regeneration and functional recovery of the damaged Central Nervous System (CNS). To study OEC antigen modulation, OECs prepared from postnatal mouse olfactory bulbs were grown in different culture conditions: standard or serum-free media with/without Growth Factors (GFs) and analyzed for different neural specific markers. OEC functional characterizations were also achieved. Resistance of OECs to the neurotoxin 6 hydroxydopamine (6-OHDA) was analyzed by evaluating apoptosis and death. OEC neuroprotective properties were investigated by in vitro co-cultures or by addition of OEC conditioned medium to the neuroblastoma SH-SY5Y cells exposed to 6-OHDA. We observed: 1) modification of OEC morphology, reduced cell survival and marker expression in serum-free medium; 2) GF addition to serum-free medium condition influenced positively survival and restored basal marker expression; 3) no OEC apoptosis after a prolonged exposition to 6-OHDA; 4) a clear OEC neuroprotective tendency, albeit non statistically significant, on 6-OHDA treated SH-SY5Y cells. These peculiar properties of OECs might render them potential clinical agents able to support injured CNS. PMID- 26553038 TI - Depleting Tumor-NQO1 Potentiates Anoikis and Inhibits Growth of NSCLC. AB - The fundamental role that NAD(P)H/quinone oxidoreductase 1 (NQO1) plays, in normal cells, as a cytoprotective enzyme guarding against stress induced by reactive oxygen species (ROS) is well documented. However, what is not known is whether the observed overexpression of NQO1 in neoplastic cells contributes to their survival. The current study discovered that depleting NQO1 expression in A549 and H292 lung adenocarcinoma cells caused an increase in ROS formation, inhibited anchorage-independent growth, increased anoikis sensitization, and decreased three-dimensional tumor spheroid invasion. These in vivo data further implicate tumor-NQO1 expression in a protumor survival role, because its depletion suppressed cell proliferation and decreased lung tumor xenograft growth. Finally, these data reveal an exploitable link between tumor-NQO1 expression and the survival of lung tumors because NQO1 depletion significantly decreased the percentage of ALDH((high)) cancer cells within the tumor population. IMPLICATIONS: Loss of tumor-NQO1 expression inhibits tumor growth and suggests that novel therapeutics directed at tumor-NQO1 may have clinical benefit. PMID- 26553039 TI - Quantitative assessment of early biomechanical modifications in diabetic foot patients: the role of foot kinematics and step width. AB - BACKGROUND: Forefoot ulcers (FU) are one of the most disabling and relevant chronic complications of diabetes mellitus (DM). In recent years there is emerging awareness that a better understanding of the biomechanical factors underlying the diabetic ulcer could lead to improve the management of the disease, with significant socio-economic impacts. Our purpose was to try to detect early biomechanical factors associated with disease progression. METHODS: Thirty subjects (M/F: 22/8; mean age +/- SD: 61,84 +/- 10 years) with diagnosis of type II DM were included. The participants were divided into 3 groups (10 subjects per group) according to the stage of evolution of the disease: Group 1, subjects with newly diagnosed type II DM, without clinical or instrumental diabetic peripheral neuropathy (DPN) nor FU (group called "DM"); Group 2, with DPN but without FU (group called "DPN"); Group 3, with DPN and FU (group called "DNU"). All subjects underwent 3-D Gait Analysis during walking at self-selected speed, measuring spatio-temporal, kinematic and kinetic parameters and focusing on ankle and foot joints. The comparative analysis of values between groups was performed using 1-way ANOVA. We also investigated group to group differences with Tukey HSD test. The results taken into consideration were those with a significance of P < 0,05. 95 % confidence interval was also calculated. RESULTS: A progressive and significant trend of reduction of ROM in flexion-extension of the metatarso-phalangeal joint (P = 0.0038) and increasing of step width (P = 0.0265) with the advance of the disease was evident, with a statistically significant difference comparing subjects with recently diagnosed diabetes mellitus and subjects with diabetic neuropathy and foot ulcer (P = 0.0048 for ROM and P = 0.0248 for step width at Tukey's test). CONCLUSIONS: The results provide evidence that foot segmental kinematics, along with step width, can be proposed as simple and clear indicators of disease progression. This can be the starting point for planning more targeted strategies to prevent the occurrence and the recurrence of a FU in diabetic subjects. PMID- 26553042 TI - [Frontal cephalgia and obstruction of nasal breathing: A rare differential diagnosis of rhinosinusitis]. PMID- 26553044 TI - Middle turbinectomy after nasotracheal intubation. AB - Nasotracheal intubation (NTI) is used for maintaining airway access during maxillofacial surgery or in cases of severe oral trauma. We describe a case of middle turbinectomy complication as a result of NTI. The purposes of this paper are to raise awareness of this complication and review associated imaging findings. PMID- 26553043 TI - Topological control of nitric oxide secretion by tantalum oxide nanodot arrays. AB - BACKGROUND: Nitric oxide (NO) plays a very important role in the cardiovascular system as a major secondary messenger in signaling pathway. Its concentration regulates most of the important physiological indexes including the systemic blood pressure, blood flow, regional vascular tone and other cardiac functions. The effect of nanotopography on the NO secretion in cardiomyocytes has not been elucidated before. In this study, we report how the nanotopography can modulate the secretion profile of NO and attempt to elucidate the genetic pathways responsible for the same by using Tantalum Oxide nanodot arrays ranging from 10 to 200 nm. A series of nanodot arrays were fabricated with dot diameter ranging from 10 to 200 nm. Temporal NO release of cardiomyocytes was quantified when grown on different surfaces. Quantitative RT-PCR and Western blot were performed to verify the genetic pathways of NO release. RESULTS: After hours 24 of cell seeding, NO release was slowly enhanced by the increase of dot diameter from 10 nm up to 50 nm, mildly enhanced to a medium level at 100 nm, and increase rapidly to a high level at 200 nm. The temporal enhancement of NO release dropped dramatically on day 3. On day 5, a topology-dependent profile was established that maximized at 50 nm and dropped to control level at 200 nm. The NO releasing profile was closely associated with the expression patterns of genes associated with Endothelial nitric oxide synthase (eNOS) pathway [GPCR, PI3K, Akt, Bad, Bcl 2, NFkappaB(p65), eNOS], but less associated with Inducible nitric oxide synthase (iNOS) pathway (TNF-alpha, ILK, Akt, IkappaBalpha, NFkappaB, iNOS). Western blotting of Akt, eNOS, iNOS, and NFkappaB further validated that eNOS pathway was modulated by nanotopology. CONCLUSIONS: Based on the findings of the present study, 50, 100 nm can serve as the suitable nanotopography patterns for cardiac implant surface design. These two nanodot arrays promote NO secretion and can also promote the vascular smooth muscle relaxation. The results of this study can improve the heart stent design in the medical treatments. PMID- 26553045 TI - Erratum to: Development of the Post Cardiac Surgery (POCAS) prognostic score. PMID- 26553046 TI - Performance evaluation of three commercial molecular assays for the detection of Mycobacterium tuberculosis from clinical specimens in a high TB-HIV-burden setting. AB - BACKGROUND: A major challenge faced by countries with a high burden of tuberculosis (TB) is early detection especially in individuals with paucibacillary disease which is common in HIV endemic settings. Remarkable efforts have been made globally to accelerate the development and expansion of new diagnostic technologies that allow better and earlier diagnosis of active tuberculosis particularly directly from clinical specimens with a few commercial options available. These include GenoType MTBDRplus Version 2.0 (Hain Lifescience), Xpert(r) MTB/RIF (Cepheid) and AnyplexTM plus MTB/NTM/DR-TB Real time detection (Seegene). We evaluated the diagnostic performance of these three commercial molecular assays for the detection of Mycobacterium tuberculosis complex from clinical specimens in a high TB-HIV-burden setting. METHODS: This was a retrospective laboratory-based study using stored remnant sediments from clinical specimens of presumptive pulmonary TB cases. A stratified sample of smear positive TB, smear negative TB and TB culture negatives was included. All the samples were tested on the three molecular assays following the manufacturers' instructions; except for AnyplexTMplus, for which DNA extraction was performed using the NucliSENS(r) easyMAG(r) platform (bioMerieux). Samples were also processed for liquid TB culture and time-to-culture positivity was recorded. RESULTS: Of the 90 sediments processed, 81 were analyzable across all three systems. The overall sensitivity was highest for Xpert(r) MTB/RIF (89.1%) followed by GenoType MTBDRplus (70.9%) and AnyplexTM plus (65.5%). The specificity and sensitivity in smear positive cases was comparable across all systems. There was a significant difference in sensitivity between Xpert(r) MTB/RIF and the other two assays for smear-negative cases (P < 0.05). The performance in cases where the time-to-culture positivity was >= 20 days was also significantly poorer for both AnyplexTM plus and GenoType MTBDRplus compared to Xpert(r) MTB/RIF (P < 0.05). Xpert(r) MTB/RIF achieved 100% specificity, while AnyplexTM plus and GenoType MTBDRplus achieved 96.2 and 92.3% respectively. CONCLUSION: The Xpert(r) MTB/RIF was superior to the other two assays for the detection of TB in smear negative specimens notably when bacterial loads are very low in sputum. It is important that studies reporting on test performance stratify their results by time-to-culture positivity to accurately assess clinical performance especially in high HIV settings. PMID- 26553047 TI - A changing climate of skepticism: The factors shaping climate change coverage in the US press. AB - Skepticism toward climate change has a long tradition in the United States. We focus on mass media as the conveyors of the image of climate change and ask: Is climate change skepticism still a characteristic of US print media coverage? If so, to what degree and in what form? And which factors might pave the way for skeptics entering mass media debates? We conducted a quantitative content analysis of US print media during one year (1 June 2012 to 31 May 2013). Our results show that the debate has changed: fundamental forms of climate change skepticism (such as denial of anthropogenic causes) have been abandoned in the coverage, being replaced by more subtle forms (such as the goal to avoid binding regulations). We find no evidence for the norm of journalistic balance, nor do our data support the idea that it is the conservative press that boosts skepticism. PMID- 26553048 TI - Histone methylation levels correlate with TGFBIp and extracellular matrix gene expression in normal and granular corneal dystrophy type 2 corneal fibroblasts. AB - BACKGROUND: TGFbeta1-induced expression of transforming growth factor beta induced protein (TGFBIp) and extracellular matrix (ECM) genes plays a major role in the development of granular corneal dystrophy type 2 (GCD2: also called Avellino corneal dystrophy). Although some key transcription factors are known, the epigenetic mechanisms modulating TGFBIp and ECM expression remain unclear. We examined the role of chromatin markers such as histone H3 lysine methylation (H3Kme) in TGFbeta1-induced TGFBIp and ECM gene expression in normal and GCD2 derived human corneal fibroblasts. METHODS: Wild-type (n = 3), GCD2-heterozygous (n = 1), and GCD2-homozygous (n = 3) primary human corneal fibroblasts were harvested from human donors and patients prepared. Microarray and gene-expression profiling, Chromatin immunoprecipitation microarray analysis, and Methylated DNA isolation assay-assisted CpG microarrays was performed in Wild-type and GCD2 homozygous human cells. RESULTS: Transcription and extracellular-secretion levels of TGFBIp were high in normal cells compared with those in GCD2-derived cells and were related to H3K4me3 levels but not to DNA methylation over the TGFBI locus. TGFbeta1 increased the expression of TGFBIp and the ECM-associated genes connective tissue growth factor, collagen-alpha2[Iota], and plasminogen activator inhibitor-1 in normal corneal fibroblasts. Increased levels of gene-activating markers (H3K4me1/3) and decreased levels of repressive markers (H3K27me3) at the promoters of those gene accompanied the changes in expression. TGFbeta1 also increased recruitment of the H3K4 methyltransferase MLL1 and of SET7/9 and also the binding of Smad3 to the promoters. Knockdown of both MLL1 and SET7/9 significantly blocked the TGFbeta1-induced gene expression and inhibited TGFbeta1 induced changes in promoter H3K4me1/3 levels. Those effects were very weak, however, in GCD2-derived corneal fibroblasts. CONCLUSIONS: Taken together, the results show the functional role of H3K4me in TGFbeta1-mediated TGFBIp and ECM gene expression in corneal fibroblasts. Pharmacologic and other therapies that regulate these modifications could have potential cornea-protective effects for granular corneal dystrophy. PMID- 26553049 TI - Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies. AB - BACKGROUND: Successful treatments of patients with somatostatin receptor (SSTR) overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. METHODS: We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. Based on these results, seven different (177)Lu-octreotate and TMZ combination schemes were evaluated for therapy response, varying the order and time interval of the two therapies and compared with single treatments. RESULTS: PRRT and TMZ both resulted in tumour size reduction, accompanied by significant changes in MRI characteristics such as an enhanced tumour perfusion. Moreover, TMZ treatment also resulted in increased uptake of the SST analogue (111)In-octreotide until day 13. In the subsequent therapy study, 90 % of animals receiving (177)Lu-TATE at day 14 after TMZ treatment showed complete response, being the best anti tumour results among groups. CONCLUSIONS: Molecular imaging studies indicated that PRRT after TMZ treatment could induce optimal therapeutic effects because of enhanced tumour uptake of radioactivity after TMZ, which was confirmed by therapy responses. Therefore, clinical translation of TMZ treatment prior to PRRT might increase tumour responses in NET patients as well. PMID- 26553050 TI - Metal and metalloid containing natural products and a brief overview of their applications in biology, biotechnology and biomedicine. AB - Bioinorganic natural product chemistry is a relatively unexplored but rapidly developing field with enormous potential for applications in biology, biotechnology (especially in regards to nanomaterial development, synthesis and environmental cleanup) and biomedicine. In this review the occurrence of metals and metalloids in natural products and their synthetic derivatives are reviewed. A broad overview of the area is provided followed by a discussion on the more common metals and metalloids found in natural sources, and an overview of the requirements for future research. Special attention is given to metal hyperaccumulating plants and their use in chemical synthesis and bioremediation, as well as the potential uses of metals and metalloids as therapeutic agents. The potential future applications and development in the field are also discussed. PMID- 26553051 TI - Adapting anatomy teaching to surgical trends: a combination of classical dissection, medical imaging, and 3D-printing technologies. AB - PURPOSE: Many regions worldwide report difficulties in recruiting applicants to surgery. One strategy proposed to reverse this trend consists of early exposure of medical students to the field. Against this backdrop, the present study presents an innovative approach for anatomy teaching, integrating a surgically relevant trend: 3D printing. METHODS: Whole-body computed tomography (CT) was made of two cadavers. Twelve students performed measurements and 3D reconstructions of selected anatomical structures (Osirix, Mimics). 3D printed (3DP) models were obtained (ZPrinter 310 Plus), and the students completed the analogous measurements on these replicas. Finally, classical anatomical dissection was performed and the same parameters were measured. The differences between the values obtained by the three modalities were submitted to standard statistical analysis (Wilcoxon two-tail paired test). RESULTS: Qualitative comparison of the digital 3D reconstructions based on the students' manual CT segmentation and the anatomical reality showed excellent correlation. Quantitatively, the values measured on the CT images and the physical models created by 3D printing differed from those measured on the cadavers by less than 2 mm. Students were highly appreciative of the approach (CT, 3DP, cadaver). Their average satisfaction score was 5.8 on a 1-6 scale. CONCLUSIONS: This study shows that the approach proposed can be achieved. The results obtained also show that CT-based 3D printed models are close to the authentic anatomic reality. The program allows early and interactive exposure of medical students to a surgically relevant trend-in this case 3D printing. PMID- 26553052 TI - Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features. AB - BACKGROUND AND AIMS: Genetic alterations in specific genes are critical events in carcinogenesis and hepatocellular carcinoma (HCC) progression. However, the genetic alterations responsible for HCC development, progression, and survival are unclear. METHODS: We investigated the essential difference in genetic alterations between HCC and adjacent non-HCC tissues using next-generation sequencing technology. RESULTS: We found recurrent mutations in several genes such as telomerase reverse transcriptase (TERT; 65% of the total 104 HCCs), TP53 (38%), CTNNB1 (30%), AXIN1 (2%), PTEN (2%), and CDKN2A (2%). TERT promoter mutations were associated with older age (p = 0.005), presence of hepatitis C virus (HCV) infection (p = 0.003), and absence of hepatitis B virus (HBV) infection (p < 0.0001). In hepatitis B surface antigen (HBs Ag)-positive HCC without TERT promoter mutations, HBV integration into TERT locus was found in 47% patients and was mutually exclusive to TERT promoter mutations. Most (89%) HBV integrants were in the HBx region. TP53 mutations were associated with HBV infection (p = 0.0001) and absence of HCV infection (p = 0.002). CTNNB1 mutations were associated with absence of HBV infection (p = 0.010). Moreover, TERT promoter mutation was significantly associated with shorter disease-free survival (p = 0.005) and poor overall survival (p = 0.024). CONCLUSIONS: Gene alterations in TERT promoter, TP53, CTNNB1, and HBV integration were closely associated with HCC development, and mutations in TERT promoter are related to poor prognosis. These results are useful for understanding the underlying mechanism of hepatocarcinogenesis, diagnosis, and predicting outcomes of patients with HCC. PMID- 26553053 TI - Percutaneous biliary drainage is oncologically inferior to endoscopic drainage: a propensity score matching analysis in resectable distal cholangiocarcinoma. AB - BACKGROUND: The aim of this study was to evaluate whether percutaneous transhepatic biliary drainage (PTBD) increases the incidence of seeding metastasis and shortens postoperative survival compared with endoscopic biliary drainage (EBD). METHODS: A total of 376 patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy following either PTBD (n = 189) or EBD (n = 187) at 30 hospitals between 2001 and 2010 were retrospectively reviewed. Seeding metastasis was defined as peritoneal/pleural dissemination and PTBD sinus tract recurrence. Univariate and multivariate analyses followed by propensity score matching analysis were performed to adjust the data for the baseline characteristics between the two groups. RESULTS: The overall survival of the PTBD group was significantly shorter than that of the EBD group (34.2 % vs 48.8 % at 5 years; P = 0.003); multivariate analysis showed that the type of biliary drainage was an independent predictor of survival (P = 0.036) and seeding metastasis (P = 0.001). After two new cohorts with 82 patients each has been generated after 1:1 propensity score matching, the overall survival rate in the PTBD group was significantly less than that in the EBD group (34.7 % vs 52.5 % at 5 years, P = 0.017). The estimated recurrence rate of seeding metastasis was significantly higher in the PTBD group than in the EBD group (30.7 % vs 10.7 % at 5 years, P = 0.006), whereas the recurrence rates at other sites were similar between the two groups (P = 0.579). CONCLUSIONS: Compared with EBD, PTBD increases the incidence of seeding metastasis after resection for distal cholangiocarcinoma and shortens postoperative survival. PMID- 26553055 TI - Lung cancer mortality and years of potential life lost among males and females over six decades in a country with high smoking prevalence: an observational study. AB - BACKGROUND: Little is known about sex-specific trends in lung cancer mortality and years of potential life lost (YPLL) attributable to lung cancer over more than five decades. The aim of the present study was to describe mortality and YPLL due to lung cancer over 61 years of observation in a country with a high smoking prevalence. METHODS: We obtained data on trends in lung cancer mortality, population-level vital statistics, sales of taxed tobacco products, and survey data on smoking behavior among the German population. We then undertook joinpoint regression analyses to determine sex-specific trends in lung cancer mortality and YPLL. RESULTS: Rates of lung cancer mortality and rates of lung cancer among all causes of death increased more among females than among males. Although YPLL among females increased from 6.6 in 1952 to 11.3 in 2012, this figure was found to have decreased from 7.3 to 4.4 among males in the same period. Sales of tobacco subject to tax increased from 1,509 cigarette equivalents per resident aged 15 or older in 1952 to 2,916 in 1976 - after which there was a decline. The prevalence of current smoking among females aged 35 years or older remained stable between 17.9 and 18.9 % in the period from 1989 to 2009. Among males in the same age group, however, prevalence decreased from 36.7 % in 1989 to 27.5 % in 2009. CONCLUSIONS: Lung cancer mortality and YPLL among females increased over the six decades studied. Women should be more considered in smoking policies. PMID- 26553054 TI - Regulation of virulence: the rise and fall of gastrointestinal pathogens. AB - Colonization resistance by the commensal microbiota is a key defense against infectious pathogens in the gastrointestinal tract. The microbiota directly competes with incoming pathogens by occupying the colonization niche, depleting nutrients in the gut lumen as well as indirectly inhibiting the growth of pathogens through activation of host immunity. Enteric pathogens have evolved strategies to cope with microbiota-mediated colonization resistance. Pathogens utilize a wide array of virulence factors to outcompete their commensal rivals in the gut. However, since the expression of virulence factors is costly to maintain and reduces bacterial fitness, pathogens need to regulate their virulence properly in order to maximize their fitness. To this end, most pathogens use environmental cues to regulate their virulence gene expression. Thus, a dynamic regulation of virulence factor expression is a key invasion strategy utilized by enteric pathogens. On the other hand, host immunity selectively targets virulent pathogens in order to counter infection in the gut. The host immune system is generally tolerant of harmless microorganisms, such as the commensal microbiota. Moreover, the host relies on its commensal microbiota to contribute, in concert with its immune system, to the elimination of pathogens. Collectively, regulation of virulence determines the fate of enteric pathogens, from the establishment of infection to the eventual elimination. Here, we will review the dynamics of virulence and its role in infection. PMID- 26553056 TI - Sequence information gain based motif analysis. AB - BACKGROUND: The detection of regulatory regions in candidate sequences is essential for the understanding of the regulation of a particular gene and the mechanisms involved. This paper proposes a novel methodology based on information theoretic metrics for finding regulatory sequences in promoter regions. RESULTS: This methodology (SIGMA) has been tested on genomic sequence data for Homo sapiens and Mus musculus. SIGMA has been compared with different publicly available alternatives for motif detection, such as MEME/MAST, Biostrings (Bioconductor package), MotifRegressor, and previous work such Qresiduals projections or information theoretic based detectors. Comparative results, in the form of Receiver Operating Characteristic curves, show how, in 70% of the studied Transcription Factor Binding Sites, the SIGMA detector has a better performance and behaves more robustly than the methods compared, while having a similar computational time. The performance of SIGMA can be explained by its parametric simplicity in the modelling of the non-linear co-variability in the binding motif positions. CONCLUSIONS: Sequence Information Gain based Motif Analysis is a generalisation of a non-linear model of the cis-regulatory sequences detection based on Information Theory. This generalisation allows us to detect transcription factor binding sites with maximum performance disregarding the covariability observed in the positions of the training set of sequences. SIGMA is freely available to the public at http://b2slab.upc.edu. PMID- 26553057 TI - Venous Thromboembolism in Patients Diagnosed With Lung Cancer. AB - PURPOSE: Considering the high prevalence of lung cancer, our purpose was to summarize the existing literature to identify the several factors that contribute to the increased risk of venous thromboembolism (VTE) in patients with lung cancer and to analyze the current recommendations for thromboprophylaxis and treatment of VTE in those patients. METHODS: We searched the Medline and EMBASE databases from February 1985 to February 2014 to identify retrospective and prospective randomized controlled studies that investigate one or more risk factors for VTEs in patients with lung cancer. RESULTS: A VTE is a major complication for patients diagnosed with lung cancer. The risk factors for VTE events in patients with lung cancer consist of cancer-related (histological type and stage of cancer), treatment-related (surgery, chemotherapy, angiogenic agents, and supportive care agents), and patient-related factors (comorbidities, immobility, performance status, and prior thrombosis). Low-molecular-weight heparins are recommended for long-term treatment of cancer-associated thrombosis. Duration of anticoagulant therapy beyond 6 months should be based on individual clinical evaluation. Thromboprophylaxis for patients with lung cancer during hospitalization and immediate postoperative period is well established. CONCLUSIONS: Efforts to assess thrombotic risk in patients with lung cancer may improve therapeutic and preventive strategies in the future, with final goal to minimize the burden and consequences of thrombotic events in patients with lung cancer. PMID- 26553059 TI - Farmers knowledge and perception on maize stem borers and their indigenous control methods in south western region of Cameroon. AB - BACKGROUND: Agriculture is a major contributor to the Gross Domestic Product (GDP) of Cameroon, The South West region of Cameroon is known for its potential in the production of major agricultural commodities, but farmers' yields from various speculations are low, dwindling over time due to some major constraints. Maize production is hampered by adverse socio-economic factors, several pests and diseases as well as high rainfall with low solar radiation. Lepidopterous maize stem borers are a major threat to increase maize production. Therefore we hypothesized that the farmers of the South West region: (1) also perceived stem borers as an important pest of maize; (2) they have their own indigenous methods of control; (3) they use chemical pesticides because they have no alternative, but would prefer plant materials if these were standardized. METHODS: A semi structured questionnaire survey was administered in four villages: Maumu, Lower Bokova, Ekona and Bonduma. A total of 151 (male and female) farmers were randomly interviewed to document farmers' perception on stem borers, and their use of indigenous knowledge to manage key pests of maize. RESULTS: Stem borers were present throughout the maize growing areas in the Fako division and ranked as one of the most important pests of the crop. Most farmers (82.1 %) perceived that stem borers caused significant damage on maize and were responsible for yield reductions in the crop. The increased impact of these pests was due to improper/untimely use of expensive conventional insecticides given the lack of a cheaper alternative method of control. About 50 % of respondent admitted not having any indigenous knowledge of stem borer control, while only 20 % had tried plant products. The most relevant indigenous stem borer control was the use of wood ash. Most (90 %) of the respondent would prefer plant-based insecticides in future because they are safer, cheaper and readily available. CONCLUSIONS: Farmers' knowledge would contribute in understanding the activities of stem borers and use of plant insecticides. Research is therefore needed to standardize the methods of using plant-based products and also identify the active ingredients of these plants to ensure their effectiveness against maize stem borers and other pests. PMID- 26553058 TI - Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility. AB - Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF alpha), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF alpha, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRalpha (PvuII) was evident only among subjects without the APOE epsilon4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE epsilon4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD. PMID- 26553060 TI - Myocardial denervation coincides with scar heterogeneity in ischemic cardiomyopathy: A PET and CMR study. AB - BACKGROUND: Mismatch between myocardial innervation and perfusion assessed with positron emission tomography (PET) is a potential risk marker for ventricular arrhythmias in patients with ischemic cardiomyopathy. This mismatch zone originates from residual viable myocardium that has sustained ischemic nerve injury. Heterogenic scar size assessed with late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR) is also a risk marker of ventricular arrhythmias. These two imaging parameters may represent identical morphological tissue features. The current study explored the relation between innervation perfusion mismatch and heterogenic scar size. METHODS: Twenty-eight patients (26 males, age 67 +/- 8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction below 35%, eligible for ICD implantation were included. All patients underwent both [11C]-hydroxyephedrine and [15O]-water PET studies to assess myocardial sympathetic innervation and perfusion. LGE CMR was conducted to assess total myocardial scar size, scar core size, and heterogenic scar size. RESULTS: Perfusion defect size was 16.6 +/- 9.9% and innervation defect size was 33.7 +/- 10.8%, which resulted in an innervation-perfusion mismatch of 17.6 +/- 8.9%. Total scar size, scar core size, and heterogenic scar size were 21.2 +/- 8.6%, 14.7 +/- 6.6%, and 6.5 +/- 2.9%, respectively. No relation between scar core size and perfusion deficit size was observed (r = 0.18, P = .36). Total scar size was correlated with the innervation defect size (r = 0.52, P = .004) and the heterogenic scar zone displayed a significant correlation with the innervation perfusion mismatch area (r = 0.67, P < .001). CONCLUSIONS: Denerved residual viable myocardium in ischemic cardiomyopathy as observed with innervation perfusion PET is related to the heterogenic scar zone as assessed with LGE CMR. PMID- 26553061 TI - Folate Receptor-Targeted Polymeric Micellar Nanocarriers for Delivery of Orlistat as a Repurposed Drug against Triple-Negative Breast Cancer. AB - Triple-negative breast cancer (TNBC) is a recalcitrant malignancy with no available targeted therapy. Off-target effects and poor bioavailability of the FDA-approved antiobesity drug orlistat hinder its clinical translation as a repurposed new drug against TNBC. Here, we demonstrate a newly engineered drug formulation for packaging orlistat tailored to TNBC treatment. We synthesized TNBC-specific folate receptor-targeted micellar nanoparticles (NP) carrying orlistat, which improved the solubility (70-80 MUg/mL) of this water-insoluble drug. The targeted NPs also improved the delivery and bioavailability of orlistat to MDA-MB-231 cells in culture and to tumor xenografts in a nude mouse model. We prepared HEA-EHA copolymer micellar NPs by copolymerization of 2 hydroxyethylacrylate (HEA) and 2-ethylhexylacrylate (EHA), and functionalized them with folic acid and an imaging dye. Fluorescence-activated cell sorting (FACS) analysis of TNBC cells indicated a dose-dependent increase in apoptotic populations in cells treated with free orlistat, orlistat NPs, and folate receptor-targeted Fol-HEA-EHA-orlistat NPs in which Fol-HEA-EHA-orlistat NPs showed significantly higher cytotoxicity than free orlistat. In vitro analysis data demonstrated significant apoptosis at nanomolar concentrations in cells activated through caspase-3 and PARP inhibition. In vivo analysis demonstrated significant antitumor effects in living mice after targeted treatment of tumors, and confirmed by fluorescence imaging. Moreover, folate receptor-targeted Fol DyLight747-orlistat NP-treated mice exhibited significantly higher reduction in tumor volume compared to control group. Taken together, these results indicate that orlistat packaged in HEA-b-EHA micellar NPs is a highly promising new drug formulation for TNBC therapy. Mol Cancer Ther; 15(2); 221-31. (c)2015 AACR. PMID- 26553062 TI - Piscivory in a Miocene Cetotheriidae of Peru: first record of fossilized stomach content for an extinct baleen-bearing whale. AB - Instead of teeth, modern mysticetes bear hair-fringed keratinous baleen plates that permit various bulk-filtering predation techniques (from subsurface skimming to lateral benthic suction and engulfment) devoted to various target prey (from small invertebrates to schooling fish). Current knowledge about the feeding ecology of extant cetaceans is revealed by stomach content analyses and observations of behavior. Unfortunately, no fossil stomach contents of ancient mysticetes have been described so far; the investigation of the diet of fossil baleen whales, including the Neogene family Cetotheriidae, remains thus largely speculative. We report on an aggregate of fossil fish remains found within a mysticete skeleton belonging to an undescribed late Miocene (Tortonian) cetotheriid from the Pisco Formation (Peru). Micro-computed tomography allowed us to interpret it as the fossilized content of the forestomach of the host whale and to identify the prey as belonging to the extant clupeiform genus Sardinops. Our discovery represents the first direct evidence of piscivory in an ancient edentulous mysticete. Since among modern mysticetes only Balaenopteridae are known to ordinarily consume fish, this fossil record may indicate that part of the cetotheriids experimented some degree of balaenopterid-like engulfment feeding. Moreover, this report corresponds to one of the geologically oldest records of Sardinops worldwide, occurring near the Tortonian peak of oceanic primary productivity and cooling phase. Therefore, our discovery evokes a link between the rise of Cetotheriidae; the setup of modern coastal upwelling systems; and the radiation of epipelagic, small-sized, schooling clupeiform fish in such highly productive environments. PMID- 26553064 TI - Gastric Cancer Regional Detection System. AB - In this study, a novel system was created to localize cancerous regions for stomach images which were taken with computed tomography(CT). The aim was to determine the coordinates of cancerous regions which spread in the stomach area in the color space with using this system. Also, to limit these areas with a high accuracy ratio and to feedback to the user of this system were the other objectives. This integration was performed with using energy mapping, analysis methods and multiple image processing methods and the system which was consisted from these advanced algorithms was appeared. For this work, in the range of 25-40 years and when gender discrimination was insignificant, 30 volunteer patients were chosen. During the formation of the system, to exalt the accuracy to the maximum level, 2 main stages were followed up. First, in the system, advanced image processing methods were processed between each other and obtained data were studied. Second, in the system, FFT and Log transformations were used respectively for the first two cases, then these transformations were used together for the third case. For totally three cases, energy distribution and DC energy intensity analysis were done and the performance of this system was investigated. Finally, with using the system's unique algorithms, a non-invasive method was achieved to detect the gastric cancer and when FFT and Log transformation were used together, the maximum success rate was obtained and this rate was calculated as 83,3119 %. PMID- 26553065 TI - A novel two-step genome editing strategy with CRISPR-Cas9 provides new insights into telomerase action and TERT gene expression. AB - BACKGROUND: To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells. RESULTS: To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step "pop-in/pop-out" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation. CONCLUSIONS: We develop a two-step CRISPR-Cas9 genome editing strategy to introduce precise modifications at the endogenous TERT locus in human cell lines. This method provides a useful tool for studying telomerase biology, and suggests a general approach to edit loci with low targeting efficiency and to purify and visualize low abundance proteins. PMID- 26553066 TI - The burden attributable to headache disorders in India: estimates from a community-based study in Karnataka State. AB - BACKGROUND: Headache disorders are common worldwide, causing pain and disability. India appears to have a very high prevalence of migraine, and of other headache disorders in line with global averages. Our objective was to estimate the burdens attributable to these disorders in order to inform health policy. METHODS: In a door-to-door survey, biologically unrelated adults (18-65 years) were randomly sampled from urban and rural areas of Bangalore and interviewed by trained researchers. The validated structured questionnaire enquired into several aspects of burden. RESULTS: Of 2,329 participants (non-participation rate 7.4 %), 1,488 (63.9 %; 621 male, 867 female) reported headache in the preceding year. Symptom burden was high. Migraine (1-year prevalence 25.2 %) occurred on average on 28 days/year but, in 38.0 % of cases (ie, 9.6 % of adults), on >=3 days/month (>=10 % of days). All causes of headache on >=15 days/month (prevalence 3.0 %) occurred on a mean of 245 days/year. Both these and migraine were rated severe in intensity. Participants with headache lost 4.3 % of productive time; those with migraine lost 5.8 % (equating to 1.5 % from the adult population). Lost paid worktime accounted for 40 % of this, probably detracting directly from GDP. We estimated population-level disability attributable to migraine using the disability weight from GBD2010 for the ictal state (0.433). Mean disability per person with migraine was 1.8 %, reducing the functional capacity of the entire adult population by 0.46 %. Fewer than one quarter of participants with headache had engaged with health-care services for headache in the last year. Actual expenditure on headache care was greatest among those with headache on >=15 days/month (especially probable medication-overuse headache), but otherwise not high. Expressed willingness to pay for effective treatment for headache was higher, signalling dissatisfaction with current treatments. CONCLUSIONS: In Karnataka State, southern India, prevalent headache disorders, especially migraine, give rise to commensurately heavy burdens. Limited access to health care fails to alleviate these. Structured headache services, with their basis in primary care, are the most efficient, effective, affordable and equitable solution. They could be implemented within the health-care infrastructure of India and are likely to be cost-saving. This solution requires political will, itself dependent on awareness. PMID- 26553067 TI - Association between a vascular endothelial growth factor gene polymorphism (rs2146323) and diabetic retinopathy: a meta-analysis. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is thought to play an important role in the pathogenesis of diabetic retinopathy (DR). Previous studies have associated the VEGF rs2146323 polymorphism with the risk of DR. However, the results of these studies are inconsistent. A meta-analysis was performed to evaluate the association between the VEGF rs2146323 polymorphism and the risk of DR. METHODS: The PubMed, EMBASE, Web of Science and Google Scholar literature databases until March 2015 were searched. The differences in the studies were expressed in the form of an odds ratio (OR) and the corresponding 95% confidence interval (CI). Heterogeneity among the studies was tested using the I(2) statistic based on the Q test. RESULTS: A total of four studies (598 cases and 709 controls) were included in the meta-analysis. A significant association was found involving the rs2146323 polymorphism in the dominant model (CA + AA VS. CC) (OR = 1.38, CI = 1.10-1.72, P = 0.005) and the co-dominant model (CA VS. CC) (OR = 1.37, CI = 1.08-1.74, P = 0.008). CONCLUSIONS: Our meta-analysis confirmed the association between the VEGF rs2146323 polymorphism and the risk of DR. PMID- 26553069 TI - Neonatal preintubation sedation: a national survey in Malaysia. AB - BACKGROUND: There is a shift of practice towards administering sedation in neonates around the world. At the present moment, there is no available data or literature on the practice of sedation before intubation of neonates in Malaysia thus, evaluation of these practice was not possible. This study was conducted to evaluate neonatal preintubation sedation practice and the availability of neonatal preintubation sedation policy in government, university and private Malaysian Neonatal Intensive Care Units (NICUs) in 2007. METHODS: All 43 NICUs in Malaysia were identified and approached to participate in the study. Phone interviews with doctors' in-charge of NICUs were conducted in 29 governments, 3 universities and in 7 private NICUs. RESULTS: Only 7 NICUs had written policy on neonatal preintubation sedation use. Seventy-seven percent and 97.4 % of NICUs used sedation during emergency intubation and during planned intubation respectively. Sixty seven percent used either morphine or midazolam with no preference of either drug. CONCLUSION: This study showed a significant proportion of NICUs used sedation during emergency or planned intubation. However, the majority does not write policy on neonatal preintubation sedation use (82.1 %). The types and drug administration methods are not standardized in all of the NICUs. This will require a standard national written policy to be developed. PMID- 26553068 TI - Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions. AB - BACKGROUND: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo resistance. METHODS: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue RESULTS: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naive cancer tissue in Western blot. CONCLUSION: Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction. PMID- 26553071 TI - Correction to "Metabolite Profiling of Bendamustine in Urine of Cancer Patients after Administration of [14C]Bendamustine". PMID- 26553070 TI - Uptake of a fluorescent L-glucose derivative 2-NBDLG into three-dimensionally accumulating insulinoma cells in a phloretin-sensitive manner. AB - Of two stereoisomers of glucose, only D- and not L-glucose is abundantly found in nature, being utilized as an essential fuel by most organisms. The uptake of D glucose into mammalian cells occurs through glucose transporters such as GLUTs, and this process has been effectively monitored by a fluorescent D-glucose derivative 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2 NBDG) at the single cell level. However, since fluorescence is an arbitrary measure, we have developed a fluorescent analog of L-glucose 2-[N-(7-Nitrobenz-2 oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), as a negative control substrate for more accurately identifying the stereoselectivity of the uptake. Interestingly, a small portion of mouse insulinoma cells MIN6 abundantly took up 2-NBDLG at a late culture stage (? 10 days in vitro, DIV) when multi-cellular spheroids exhibiting heterogeneous nuclei were formed, whereas no such uptake was detected at an early culture stage (? 6 DIV). The 2-NBDLG uptake was persistently observed in the presence of a GLUT inhibitor cytochalasin B. Neither D- nor L glucose in 50 mM abolished the uptake. No significant inhibition was detected by inactivating sodium/glucose cotransporters (SGLTs) with Na(+)-free condition. To our surprise, the 2-NBDLG uptake was totally inhibited by phloretin, a broad spectrum inhibitor against transporters/channels including GLUTs and aquaporins. From these, a question might be raised if non-GLUT/non-SGLT pathways participate in the 2-NBDLG uptake into spheroid-forming MIN6 insulinoma. It might also be worthwhile investigating whether 2-NBDLG can be used as a functional probe for detecting cancer, since the nuclear heterogeneity is among critical features of malignancy. PMID- 26553072 TI - Enhanced Detection of Antigen-Specific CD4+ T Cells Using Altered Peptide Flanking Residue Peptide-MHC Class II Multimers. AB - Fluorochrome-conjugated peptide-MHC (pMHC) class I multimers are staple components of the immunologist's toolbox, enabling reliable quantification and analysis of Ag-specific CD8(+) T cells irrespective of functional outputs. In contrast, widespread use of the equivalent pMHC class II (pMHC-II) reagents has been hindered by intrinsically weaker TCR affinities for pMHC-II, a lack of cooperative binding between the TCR and CD4 coreceptor, and a low frequency of Ag specific CD4(+) T cell populations in the peripheral blood. In this study, we show that peptide flanking regions, extending beyond the central nonamer core of MHC-II-bound peptides, can enhance TCR-pMHC-II binding and T cell activation without loss of specificity. Consistent with these findings, pMHC-II multimers incorporating peptide flanking residue modifications proved superior for the ex vivo detection, characterization, and manipulation of Ag-specific CD4(+) T cells, highlighting an unappreciated feature of TCR-pMHC-II interactions. PMID- 26553073 TI - Structural and Functional Changes of the Invariant NKT Clonal Repertoire in Early Rheumatoid Arthritis. AB - Invariant NKT cells (iNKT) are potent immunoregulatory T cells that recognize CD1d via a semi-invariant TCR (iNKT-TCR). Despite the knowledge of a defective iNKT pool in several autoimmune conditions, including rheumatoid arthritis (RA), a clear understanding of the intrinsic mechanisms, including qualitative and structural changes of the human iNKT repertoire at the earlier stages of autoimmune disease, is lacking. In this study, we compared the structure and function of the iNKT repertoire in early RA patients with age- and gender-matched controls. We analyzed the phenotype and function of the ex vivo iNKT repertoire as well as CD1d Ag presentation, combined with analyses of a large panel of ex vivo sorted iNKT clones. We show that circulating iNKTs were reduced in early RA, and their frequency was inversely correlated to disease activity score 28. Proliferative iNKT responses were defective in early RA, independent of CD1d function. Functional iNKT alterations were associated with a skewed iNKT-TCR repertoire with a selective reduction of high-affinity iNKT clones in early RA. Furthermore, high-affinity iNKTs in early RA exhibited an altered functional Th profile with Th1- or Th2-like phenotype, in treatment-naive and treated patients, respectively, compared with Th0-like Th profiles exhibited by high-affinity iNKTs in controls. To our knowledge, this is the first study to provide a mechanism for the intrinsic qualitative defects of the circulating iNKT clonal repertoire in early RA, demonstrating defects of iNKTs bearing high-affinity TCRs. These defects may contribute to immune dysregulation, and our findings could be exploited for future therapeutic intervention. PMID- 26553074 TI - The Bacterial Enzyme IdeS Cleaves the IgG-Type of B Cell Receptor (BCR), Abolishes BCR-Mediated Cell Signaling, and Inhibits Memory B Cell Activation. AB - Ag binding to the BCR is a critical step in B cell development and activation, initiating a cascade of signaling events ultimately leading to proliferation, differentiation, or cell death. A bacterial enzyme, IgG-degrading enzyme of Streptococcus pyogenes (IdeS), was shown to specifically cleave IgG molecules below the hinge region of soluble IgG and when IgG is bound to Ag, resulting in one F(ab')2 molecule and one homodimeric Fc fragment. Whether IdeS could also cleave the IgG molecule when it is present in the BCR attached to the B cell membrane in a complex with CD79a and CD79b is unknown. In this article, we present human in vitro and ex vivo data showing that IdeS cleaves the IgG present in the BCR complex and very efficiently blocks Ag binding to the BCR. As a consequence of IdeS cleaving the BCR, signaling cascades downstream of the BCR are blocked, and memory B cells are temporarily silenced, preventing them from responding to antigenic stimulation and their transition into Ab-producing cells. PMID- 26553075 TI - Compensatory Regulatory Networks between CD8 T, B, and Myeloid Cells in Organ Transplantation Tolerance. AB - In transplantation tolerance, numerous regulatory populations have the capacity to inhibit allograft rejection; however, their compensatory capacities have never been clearly evidenced. We have previously demonstrated that the tolerogenic effect mediated by CD8(+)CD45RC(low) regulatory T cells (Tregs) in a model of organ transplantation with CD40Ig could be abrogated by permanent depletion of CD8(+) cells that resulted in allograft rejection in half of the recipients. This result demonstrated that CD8(+) Tregs were essential, but also that half of the recipients still survived indefinitely. We also demonstrated that no other regulatory populations, besides CD8(+) Tregs, could induce and maintain allograft tolerance in CD40Ig-treated tolerant animals. In the current study, we analyzed the mechanisms that arose following CD8(+) Treg depletion and allowed establishment of networks of new regulatory cells to maintain allograft survival. We identified regulatory B cells (Bregs) and regulatory myeloid cells (RegMCs) as being responsible of the maintenance of the long-term allograft survival. We demonstrated that both regulatory cell subsets efficiently inhibited antidonor immune responses in adoptively transferred recipients. Although Bregs were induced, they were not essential for the maintenance of the graft as demonstrated in IgM-deficient recipients. In addition, we showed that RegMCs were the most suppressive and acted alone, whereas Bregs activity was associated with increased suppressive activity of other subsets in adoptively transferred recipients. Altogether, to our knowledge, we demonstrated in this study for the first time the emergence of both Bregs and RegMCs following Tregs depletion and highlighted the importance of regulatory cell networks and their synergistic potential in transplantation. PMID- 26553076 TI - Estrogen Receptor alpha Deficiency Modulates TLR Ligand-Mediated PDC-TREM Expression in Plasmacytoid Dendritic Cells in Lupus-Prone Mice. AB - Female lupus-prone NZM2410 estrogen receptor alpha (ERalpha)-deficient mice are protected from renal disease and have prolonged survival compared with wild-type littermates; however, the mechanism of protection is unknown. Plasmacytoid dendritic cells (pDCs) and type I IFN drive lupus pathogenesis. Estrogen acting via ERalpha enhances both pDC development and IFN production. The objectives for this study were to determine if ERalpha modulates pDC function and IFN activity in predisease NZM2410 mice as a possible protective mechanism of ERalpha deficiency in lupus-prone mice. We measured the effect of ERalpha deficiency on spleen pDC frequency, number, maturation, and activation state. ERalpha deficiency reduced type I IFN activity and the frequency of MHC class II(+) pDCs in the spleen without altering overall pDC frequency, number, or maturation state. Additionally, ERalpha-deficient NZM2410 mice had a significantly decreased frequency of pDCs expressing PDC-TREM, a modulator of TLR-mediated IFN production. After in vitro TLR9 stimulation, ERalpha deficiency significantly reduced the expression of PDC-TREM on pDCs from both NZM2410 and C57BL/6 mice. Thus, we have identified a significant effect of ERalpha deficiency on pDCs in predisease NZM2410 mice, which may represent a mechanism by which ERalpha deficiency protects NZM2410 mice from lupuslike disease. PMID- 26553077 TI - Determining the origin of synchronous multifocal bladder cancer by exome sequencing. AB - BACKGROUND: Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours. METHODS: To better understand the genetic lineage of these tumours we conducted exome sequencing of synchronous multifocal pTa urothelial bladder cancers at a high depth, using multiple samples from three patients. RESULTS: Phylogenetic analysis of high confidence single nucleotide variants (SNV) demonstrated that the sequenced multifocal bladder cancers arose from a clonal origin in all three patients (bootstrap value 100 %). Interestingly, in two patients the most common type of tumour-associated SNVs were cytosine mutations of TpC* dinucleotides (Fisher's exact test p < 10(-41)), likely caused by APOBEC-mediated deamination. Incorporating these results into our clonal model, we found that TpC* type mutations occurred 2-5* more often among SNVs on the ancestral branches than in the more recent private branches (p < 10(-4)) suggesting that TpC* mutations largely occurred early in the development of the tumour. CONCLUSIONS: These results demonstrate that synchronous multifocal bladder cancers frequently arise from a clonal origin. Our data also suggests that APOBEC-mediated mutations occur early in the development of the tumour and may be a driver of tumourigenesis in non-muscle invasive urothelial bladder cancer. PMID- 26553078 TI - US Senate committee launches investigation into drug pricing. PMID- 26553079 TI - Assessing the Fauna of Aquatic Insects for Possible Use for Malaria Vector Control in Large River, Central Iran. AB - Insects with over 30,000 aquatic species are known as very successful arthropods in freshwater habitats. Some of them are applied as biological indicators for water quality control, as well as the main food supply for fishes and amphibians. The faunistic studies are the basic step in entomological researches; the current study was carried out emphasizing on the fauna of aquatic insects in Karaj River, northern Iran. A field study was carried out in six various sampling site of Karaj River during spring 2013. The aquatic insects were collected using several methods such as D-frame nets, dipping and direct search on river floor stones. Specimens were collected and preserved in Ethanol and identified by standard identification keys. Totally, 211 samples were collected belonging to three orders; Plecoptera, Trichoptera and Ephemeroptera. Seven genuses (Perla, Isoperla, Hydropsyche, Cheumatopsyche, Baetis, Heptagenia and Maccafferium) from five families (Perlidae, Perlodidae, Hydropsychidae, Batidae, Heptagenidae) were identified. The most predominant order was Plecoptera followed by Trichoptera. Karaj River is a main and important river, which provides almost all of water of Karaj dam. So, identification of aquatic species which exist in this river is vital and further studies about systematic and ecological investigations should be performed. Also, monitoring of aquatic biota by trained health personnel can be a critical step to describe water quality in this river. Understanding the fauna of aquatic insects will provide a clue for possible biological control of medically important aquatic insects such as Anopheles as the malaria vectors. PMID- 26553080 TI - Remyelination of the Corpus Callosum by Olfactory Ensheathing Cell in an Experimental Model of Multiple Sclerosis. AB - Multiple Sclerosis (MS) causes loss of the myelin sheath, which leads to loss of neurons. Regeneration of myelin sheath stimulates axon regeneration and neurons' survival. In this study, olfactory ensheathing cell (OEC) transplantation is investigated to restore myelin sheath in an experimental model of MS in male mice.OECs were isolated from the olfactory mucosa of seven-day-old infant rats and cultured. Then, cells were evaluated and approved by flow cytometry by p75 and GFAP markers. A total of 32 mice (C57BL /6) were studied in four groups; 1) without any treatment (control), 2) Sham (receiving PBS), 3) MS model and 4) MS and OEC transplantation. MS was induced by adding Cuprizon in the diet of animals for six weeks. After the expiration of 20 days, histologic analysis was performed with approval of the presence of cells in the graft area and the removal of myelin and myelin regeneration with two types of luxal fast blue (LFB) staining and immunohistochemistry. The purity of the cells ensheathing the olfactory was 90%. There was a significant difference in Myelin percentage of PBS and OEC recipient groups (P<=0.05). MBP and PLP of the myelin sheath in the group receiving OECs were more than MS group.According to the findings, in MS model MBP and PLP of the myelin sheath is reduced. In the group receiving OECs, it was returned to a normal level significantly compared to the sham group received only PBS significant differences were observed. The OECs transplantation can improve myelin restoration. PMID- 26553081 TI - Clinical Grade Human Adipose Tissue-Derived Mesenchymal Stem Cell Banking. AB - In this study, our aim was to produce a generation of GMP-grade adipose tissue derived mesenchymal stem cells for clinical applications. According to our results, we fulfill to establish consistent and also reproducible current good manufacturing practice (cGMP) compliant adipose tissue-derived mesenchymal stem cells from five female donors. The isolated cells were cultured in DMEM supplemented with 10% fetal bovine serum and characterized by standard methods. Moreover, karyotyping was performed to evaluate chromosomal stability. Mean of donors' age was 47.6 +/- 8.29 year, mean of cell viability was 95.6 +/- 1.51%, and cell count was between 9*106 and 14*106 per microliter with the mean of 12.2*106 +/- 2863564.21 per microliter. The main aim of this project was demonstrating the feasibility of cGMP-compliant and clinical grade adipose tissue derived mesenchymal stem cells preparation and banking for clinical cell transplantation trials. PMID- 26553082 TI - Do Pilea Microphylla Improve Sperm DNA Fragmentation and Sperm Parameters in Varicocelized Rats? AB - Varicocele is one of the most common causes of primary male infertility. Pilea microphylla (PM) is being used as folk medicine. This study was aimed to investigate the effects of PM in a rat model of varicocele. A total of 30 male Wistar rats were divided into control, sham, varicocele, accessory varicocele and PM-treated groups. After 10 weeks of varicocele induction, sperm parameters and chromatin (Aniline blue, acridine orange and toluidine blue) were evaluated, except for the treated and accessory groups that received 50 mg/kg PM orally daily for 10 weeks and then were sacrificed. Sperm parameters significantly decreased in varicocele groups (P < 0.01). Moreover, there was a negative correlation between the DNA fragmentation and sperm parameters in varicocelized rats. Administration of PM led to significantly increased sperm parameters and AO staining (P < 0.05). These findings suggest that PM improves sperm parameters and DNA fragmentation in varicocelized rats. PM can reduce the damage to sperm DNA but not chromatin condensation. PMID- 26553083 TI - Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage. AB - Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-p content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-p in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P<=0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P<=0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and decreases their numbers. Enrofloxacin use in growing lambs even at recommended therapeutic dose is not completely safe on articular cartilage. Moreover, higher doses of enrofloxacin induce severe changes in lamb articular cartilage. PMID- 26553084 TI - The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit. AB - The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups. PMID- 26553085 TI - Effect of Intravenous Dexamethasone on Preparing the Cervix and Labor Induction. AB - The use of corticosteroids is one of the methods put forward for the strengthening and speeding up the process of labor. After identification of glucocorticoid receptors in human amnion, the role of corticosteroids in starting the process of labor has been studied in numerous studies. The purpose of this study was to determine the effect of intravenous Dexamethasone on preparing the cervix and on labor induction. A randomized, clinical, and double-blind trial was conducted on 172 women divided into a control and an experimental group. The inclusion criteria were that they had to be primparous, in or before the 40th week of pregnancy, and with Bishop scores (B.S.s) of 4 or lower. The exclusion criteria were diabetes, preeclampsia, macrosomia, twin pregnancy, rupture of the membrane (ROM), breech, and women suffering from background diseases. The B.S.s of the women was measured in charge of the study, and each woman was intravenously injected with eight milligrams of Dexamethasone or eight milligrams of distilled water. Four hours after the injections, the B.S.s of the participants was measured, and they were put under the conditions of labor induction using oxytocin. Information was collected in checklists A and B. The patients were compared with respect to B.S., the time the induction started, the average interval between the start of induction and the beginning of the active phase of childbirth, and the average length of time between the start of the active phase and the second stage of childbirth. The first and five minutes Apgar scores of the two groups of women were compared. The frequencies, the means, and the standard deviations were calculated using the SPSS - 16 software, and analysis of the results was performed with the Student's t- test and the chi square test with with P<0.05. There were no statistically significant differences between the two groups in terms of their age, period of pregnancy, and B.S. at the start of the study. The average B.S. of women four hours after the injections with Dexamethasone was 5.9 +/- 1.57, and the corresponding figure for women in the control group was 4.6 +/- 1.72. These figures were significantly different at P<0.001. The average interval between labor induction and the start of the active phase in the group injected with Dexamethasone was significantly less than that of the control group (2.87+/-0.93 versus 3.80+/- 0.93 at P<0.001). The average duration of the active phase of the second stage of childbirth was 3.47+/-1.10 hours in the experimental group and 3.6 +/- 0.99 hours in the control group at P<0.49. These two figures were not significantly different. The Apgar scores of the first and fifth minutes after the birth of the children of the two groups of women were not significantly different. It was found that intravenous Dexamethasone improves the Bishop score of the cervix and thus causes softening of the cervix and reduces the length of time between labor induction and the start of the active phase of childbirth. PMID- 26553086 TI - Effect of Zolpidem on Sleep Quality of Professional Firefighters; a Double Blind, Randomized, Placebo-Controlled Crossover Clinical Trial. AB - Professional firefighting is among the most demanding jobs. Prior studies have showed the notable prevalence of poor sleep quality among professional firefighters that may result in catastrophes. The aim of this study was in field confirmation of zolpidem usage (10 mg/PO/bed time) for short term management of poor sleeps quality among professional firefighters. In a double-blind, randomized, placebo-controlled crossover clinical trial among professional firefighters, 27 poor sleepers were assigned randomly to one of the two groups. Two 14 days experimental periods were separated by a 14-day washout phase. Sleep quality was assessed using the Persian version of Pittsburgh Sleep Quality Index (PSQI). Six of the 27 enrolled voluntaries dropped out. Two rare side effects of zolpidem occurred in the study. A significant improvement of the PSQI score was detected in zolpidem period versus placebo in both groups (7.14 +/- 3.02 vs 12.38 +/- 2.51, P<0.001) although zolpidem had no significant effect on time of waking up (6.76 +/- 1.21 vs.6.64 +/- 1.27, P=0.89). Zolpidem significantly improved all components of PSQI (Subjective sleep quality, Sleep latency, Sleep duration, Habitual sleep efficiency, Sleep disturbances and Daytime dysfunction) in the current study except the use of sleep medication. Sleep onset latency was the component of PSQI with the greatest degree of abnormality among firefighters in a previous study. Interestingly, sleep latency was the component of PSQI with the most treatment effect of zolpidem in the current study. Zolpidem can be used asa part of treatment regimens in short time management of poor sleep quality among professional firefighters. PMID- 26553087 TI - Comparative Evaluation of Corrected QT and Ionized Calcium in Children. AB - Convulsion is one of the most common problems in children and hypocalcemia is one the most frequent etiological items in children's convulsion. Corrected QT (QTc) in EKG is prolonged in hypocalcemia, so it can be a useful tool for evaluation of serum ionized calcium. In three groups (first seizure, multiple seizures, without seizure or control ) every 25 cases, QTc, serum ionized ca, total ca, ABG, and serum albumin level have been checked in the Department of Pediatrics of Imam Khomeini Hospital and outpatient department of Ahari children's medical center in 2008. Prolonged QTc was observed in 72% of convulsive children (36 cases) but only 19% of non-convulsive children (5 cases) showed this pattern. Ionized calcium was significantly higher in non-convulsive than convulsive groups. There was no correlation between prolonged QTc and total serum calcium; however, this correlation with low ionized calcium was significant. QTc is an easy and rapid method for serum ionized calcium evaluation. PMID- 26553088 TI - Sleep Problems Under-Reported by Parents in Iranian Children. AB - Sleep problems are common in childhood, but there are limited studies regarding that in Iranian children and awareness of the sleep problems and their complication in Iranian parents. We arranged this study in which parents of children attending for a sick visit or routine growth control to assess whether sleep problems are under-reported at general pediatric visits. In a cross sectional study from April 2010 to April 2011 in 301 children aged 2-14 years old attending to pediatric clinics were enrolled. To investigate the general orientation of parents about their child sleep problem we asked them a global question at first regarding sleep of their child. After that, the Persian version of BEARS questionnaire was completed by them. Only 30 (9.9%) parents reported sleep problems in their children in response to primary global question but by collecting the data from BEARS questionnaire it was revealed 45.18% (136/301) of children had one or more of sleep disorders at all. As mentioned 136 (45.18%) children had slept problems of which the most frequent complaint (15.28%) was related to bedtime problems. The second complaint (11.96%) was awakening during the night children. A significant association between sleep problems and child gender was not found. Co-sleeping with parents was found in 55.48% of all children in this study. Despite the high prevalence and adverse effects of sleep disorders, the present study suggests that parents underreport sleep problems at consultation. We suggest children should be assessed for sleep disorders in monitoring and health screening visits. PMID- 26553089 TI - Hemolytic Anemia after Aortic Valve Replacement: a Case Report. AB - Hemolytic anemia is exceedingly rare and an underestimated complication after aortic valve replacement (AVR).The mechanism responsible for hemolysis most commonly involves a regurgitated flow or jet that related to paravalvar leak or turbulence of subvalvar stenosis. It appears to be independent of its severity as assessed by echocardiography. We present a case of a 24-year-old man with a history of AVR in 10 year ago that developed severe hemolytic anemia due to a mild subvalvar stenosis caused by pannus formation and mild hypertrophic septum. After exclusion of other causes of hemolytic anemia and the lack of clinical and laboratory improvement, the patient underwent redo valve surgery with pannus and subvalvar hypertrophic septum resection. Anemia and heart failure symptoms gradually resolved after surgery. PMID- 26553090 TI - Impending Complete Airway Obstruction from a Reinforced Orotracheal Tube: a Case Report. AB - Reinforced tubes are commonly used to minimize the opportunity of upper airway obstruction in patients at risk. There are a few reports of the airway obstruction resulted from kinked reinforced tubes. This report describes the obstruction of a reinforced tube in an adult patient who underwent tonsillectomy. Under general anesthesia; an armoured endotracheal tube was inserted into the trachea uneventfully. A few minutes after starting the surgery, the anesthesia machine detected a high airway pressure and an increased ETCO2 (end-tidal CO2) up to 50 mmHg. Further evaluation showed spiral wire damage resulted from Mouth Gag device that led to airway obstruction. Early anticipation of the complications leads to proper management of such critical and life threatening complications and prevention of hypoxia, hypercapnia, pneumothorax, and pulmonary edema. Based on our experience using an armoured endotracheal tube in tonsillectomy does not guarantee a safe airway and intensive monitoring is necessary. PMID- 26553091 TI - Erratum: Indeterminate Cell Histiocytosis: Report of a Case. PMID- 26553093 TI - Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice. AB - The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns. PMID- 26553092 TI - Behaviour change strategies for reducing blood pressure-related disease burden: findings from a global implementation research programme. AB - BACKGROUND: The Global Alliance for Chronic Diseases comprises the majority of the world's public research funding agencies. It is focussed on implementation research to tackle the burden of chronic diseases in low- and middle-income countries and amongst vulnerable populations in high-income countries. In its inaugural research call, 15 projects were funded, focussing on lowering blood pressure-related disease burden. In this study, we describe a reflexive mapping exercise to identify the behaviour change strategies undertaken in each of these projects. METHODS: Using the Behaviour Change Wheel framework, each team rated the capability, opportunity and motivation of the various actors who were integral to each project (e.g. community members, non-physician health workers and doctors in projects focussed on service delivery). Teams then mapped the interventions they were implementing and determined the principal policy categories in which those interventions were operating. Guidance was provided on the use of Behaviour Change Wheel to support consistency in responses across teams. Ratings were iteratively discussed and refined at several group meetings. RESULTS: There was marked variation in the perceived capabilities, opportunities and motivation of the various actors who were being targeted for behaviour change strategies. Despite this variation, there was a high degree of synergy in interventions functions with most teams utilising complex interventions involving education, training, enablement, environmental restructuring and persuasion oriented strategies. Similar policy categories were also targeted across teams particularly in the areas of guidelines, communication/marketing and service provision with few teams focussing on fiscal measures, regulation and legislation. CONCLUSIONS: The large variation in preparedness to change behaviour amongst the principal actors across these projects suggests that the interventions themselves will be variably taken up, despite the similarity in approaches taken. The findings highlight the importance of contextual factors in driving success and failure of research programmes. Forthcoming outcome and process evaluations from each project will build on this exploratory work and provide a greater understanding of factors that might influence scale-up of intervention strategies. PMID- 26553094 TI - The Nicaraguan pediatric influenza cohort study: design, methods, use of technology, and compliance. AB - BACKGROUND: Influenza causes substantial morbidity and mortality worldwide, yet few data exist on influenza infection rates in tropical, developing countries. In 2011, we established the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to study the burden and seasonality of influenza in Nicaraguan children. Here we describe the study design, methods, and participation data of the NPICS for 2011 2013. METHODS/DESIGN: A total of 1532 children aged 0 to 12 years were enrolled into the study in 2011, and an additional 401 children were enrolled between 2012 and 2013. Children were provided with all of their medical care through the study, and data on medical visits were recorded systematically. A number of surveys were conducted together with a blood sample annually, including a height and weight measurement, a socio-economic status and risk factor survey, and a breastfeeding survey. DISCUSSION: Unique features of our study include the customized low-cost, open-source informatics system as well as the development of methods to leverage infrastructure and resources by conducting multiple studies in the same setting while maximizing protocol adherence and quality control. These methods should be useful to others conducting large cohort studies, particularly in low-resource settings. PMID- 26553095 TI - In vitro antioxidant and cholinesterase inhibitory activities of methanolic fruit extract of Phyllanthus acidus. AB - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by loss of memory and cognition. Cholinergic deficit and oxidative stress have been implicated in the pathogenesis of AD. Therefore, inhibition of acetylcholinesterase and oxidation are the two promising strategies in the development of drug for AD. Phyllanthus acidus, belonging to the family Euphorbiaceae, is a tree and has been used in traditional medicine to treat several pain, inflammatory and oxidative stress related disorders such as rheumatism, bronchitis, asthma, respiratory disorder, also important to promote intellect and enhance memory, thus supporting its possible anti-Alzheimer's properties. In this study, P. acidus was evaluated for its cholinesterase inhibitory and antioxidant activities. METHODS: In this study, we evaluated the antioxidant potential and neuroprotective activity of P. acidus by assessing total phenol content (FCR assay), total flavonoid content, total antioxidant capacity, Fe (3+) reducing power capacity, DPPH (2, 2-diphenyl-1-picrylhydrazyl) and hydroxyl radical scavenging capacity, lipid peroxidation inhibition activity & metal chelating activity. In addition acetylcholinestrase (AChE) and butyrylcholinestrase (BChE) inhibitory activities were performed using Ellman's method. RESULTS: Total phenolic content and total flavonoid content of the extract were 116.98 mg of gallic acid equivalent and 168.24 mg of quercetin equivalent per gm of dried extract. The methanolic extract of P. acidus (MEPA) showed considerable total antioxidant activity and reducing capacity. In DPPH scavenging assay and hydroxyl radical scavenging assay, the MEPA showed 84.33 % and 77.21 % scavenging having IC50 of 15.62 and 59.74 MUg/ml respectively. In lipid peroxidation inhibition activity MEPA showed moderate inhibition of peroxidation at all concentrations with IC50 value of 471.63 MUg/ml and exhibited metal chelating activity with IC50 value 308.67 MUg/ml. The MEPA exhibited inhibition of rat brain acetylcholinesterase and human blood butyrylcholinesterase in a dose dependent manner and the IC50 value was found to be 1009.87 MUg/ml and 449.51 MUg/ml respectively. CONCLUSION: These results of the present study reveal that MEPA has considerable amount of antioxidant activity as well as anti-acetylcholinesterase and anti-butyrylcholinesterase activity which suggest its effectiveness against Alzheimer's disease and other neurodegenerative disorders. PMID- 26553096 TI - Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans. AB - AIMS/HYPOTHESIS: Type 2 diabetes is closely associated with pathological lipid accumulation in the liver, which is suggested to actively contribute to the development of insulin resistance. We recently identified serine/threonine protein kinase 25 (STK25) as a regulator of liver steatosis, whole-body glucose tolerance and insulin sensitivity in a mouse model system. The aim of this study was to assess the role of STK25 in the control of lipid metabolism in human liver. METHODS: Intracellular fat deposition, lipid metabolism and insulin sensitivity were studied in immortalised human hepatocytes (IHHs) and HepG2 hepatocellular carcinoma cells in which STK25 was overexpressed or knocked down by small interfering RNA. The association between STK25 mRNA expression in human liver biopsies and hepatic fat content was analysed. RESULTS: Overexpression of STK25 in IHH and HepG2 cells enhanced lipid deposition by suppressing beta oxidation and triacylglycerol (TAG) secretion, while increasing lipid synthesis. Conversely, knockdown of STK25 attenuated lipid accumulation by stimulating beta oxidation and TAG secretion, while inhibiting lipid synthesis. Furthermore, TAG hydrolase activity was repressed in hepatocytes overexpressing STK25 and reciprocally increased in cells with STK25 knockdown. Insulin sensitivity was reduced in STK25-overexpressing cells and enhanced in STK25-deficient hepatocytes. We also found a statistically significant positive correlation between STK25 mRNA expression in human liver biopsies and hepatic fat content. CONCLUSIONS/INTERPRETATION: Our data suggest that STK25 regulates lipid partitioning in human liver cells by controlling TAG synthesis as well as lipolytic activity and thereby NEFA release from lipid droplets for beta oxidation and TAG secretion. Our findings highlight STK25 as a potential drug target for the prevention and treatment of type 2 diabetes. PMID- 26553097 TI - The Antiproliferative and Pro-apoptotic Effects of Methoxyamine on Pediatric Medulloblastoma Cell Lines Exposed to Ionizing Radiation and Chemotherapy. AB - Medulloblastoma (MB) treatment is continuously evolving. Better treatment approaches, focused on particular molecular pathways involved in MB development and progression support new treatment strategies. This article explores the antiproliferative, proapoptotic and radiosensitizing effects of Methoxyamine (MX), a base excision repair (BER) inhibitor that has shown anticancer potential by sensitizing tumor cells to ionizing radiation and chemotherapy. The DAOY (a desmoplastic cerebellar-derived MB) and ONS-76 (classical MB) cell lines were treated with MX at different concentrations, either alone or combined with various chemotherapeutic compounds: cisplatin (CDDP), temozolomide (TMZ) and thiotepa (THIO). Additionally, cell lines were exposed to MX and treated at different ionizing radiation fractions. Measurement of cell growth by XTT assay, clonogenic assay and detection of apoptotic cell death through caspase activity was obtained. Exposure to MX significantly decreased cell proliferation (p<0.05) while increasing cell apoptosis (p<0.05). Growth reduction was concentration dependent for both DAOY and ONS-76 cells lines. Conversely, MX failed to enhance the cytotoxicity of CDDP, TMZ, and THIO. Moreover, MX treatment radiosensitized both cell lines, with ONS-76 cells being more prone to radiation effects at higher doses of exposure. These data support the role of MX as a direct cytotoxic compound for pediatric MB cells by inhibiting the BER pathway. Nevertheless, an antagonism, rather than a synergic or additive effect of MX with different concentrations of CDDP, TMZ and THIO was observed. Likewise, the radiosensitizing effect on MB cell lines seems to depend on radiation doses and MB subtype. This information may be relevant for clinical study designs employing BER inhibitors for MB. PMID- 26553099 TI - High-throughput blood cell focusing and plasma isolation using spiral inertial microfluidic devices. AB - Herein, we explored the blood cell focusing and plasma isolation using a spiral inertial microfluidic device. First, the flow-rate and concentration effects on the migration dynamics of blood cells were systematically investigated to uncover the focusing mechanisms and steric crowding effects of cells in Dean-coupled inertial flows. A novel phenomenon that the focusing status of discoid red blood cells (RBCs) changes according to the channel height was discovered. These experimental data may provide valuable insights for the high-throughput processing of blood samples using inertial microfluidics. On the basis of the improved understandings on blood cell focusing, efficient isolation of plasma from whole blood with a 20-fold dilution was achieved at a throughput up to 700 MUl/min. The purity of the isolated blood plasma was close to 100 %, and the plasma yield was calculated to be 38.5 %. As compared with previously-reported devices, our spiral inertial microfluidic device provides a balanced overall performance, and has overriding advantages in terms of processing throughput and operating efficiency. PMID- 26553098 TI - Altered Gray Matter in Adolescents with d-Transposition of the Great Arteries. AB - OBJECTIVE: To investigate the structural brain characteristics of adolescent patients with d-transposition of the great arteries (d-TGA), repaired with the arterial switch operation in early infancy, using quantitative volumetric magnetic resonance imaging. STUDY DESIGN: Ninety-two patients with d-TGA from the Boston Circulatory Arrest Study (76% male; median age at scan 16.1 years) and 49 control subjects (41% male; median age at scan 15.7 years) were scanned using a 1.5-Tesla magnetic resonance imaging system. Subcortical and cortical gyral volumes and cortical gyral thicknesses were measured using surface-based morphometry. Group differences were assessed with linear regression. RESULTS: Compared with controls, patients with d-TGA demonstrated significantly reduced subcortical volumes bilaterally in the striatum and pallidum. Cortical regions that showed significant volume and thickness differences between groups were distributed throughout parietal, medial frontoparietal, cingulate, and temporal gyri. Among adolescents with d-TGA, volumes and thicknesses correlated with several perioperative variables, including age at surgery, cooling duration, total support time, and days in the cardiac intensive care unit. CONCLUSIONS: Adolescents with d-TGA repaired early in life exhibit widespread differences from control adolescents in gray matter volumes and thicknesses, particularly in parietal, midline, and subcortical brain regions, corresponding to white matter regions already known to demonstrate altered microstructure. These findings complement observations made in white matter in this group and suggest that the adolescent d-TGA cognitive profile derives from altered brain development involving both white and gray matter. PMID- 26553100 TI - Extended-gate field-effect transistor packed in micro channel for glucose, urea and protein biomarker detection. AB - This study developed a packaging method to integrate the extended-gate field effect transistor (EGFET) into a microfluidic chip as a biological sensor. In addition, we present two immobilization approaches for the bio-recognition that are appropriate to this chip, allowing it to measure the concentrations of hydrogen ions, glucose, urea, and specific proteins in a solution. Alginate calcium microcubes were used to embed the enzymes and magnetic powder (enzyme carrier). When the sensing chip needs the enzyme for the catalytic reaction, the alginate microcubes containing the corresponding enzymes enter through the flow channel and are immobilized on the EGFET surface with an external magnet. High sensing performance of the chip is achieved, with 37.45 mV/mM for measuring hydrogen ions at pH 6-8 with a linearity of 0.9939, 7.00 mV/mM for measuring glucose with a linearity of 0.9962, and 8.01 mV/mM for measuring urea with a linearity of 0.9809. In addition, based on the principle of the immunoassay, the magnetic beads with the specific antibody were used to capture the target protein in the sample. Then, negatively charged DNA fragments bound to a secondary antibody were used to amplify the signal for EGFET measurement. The magnetic beads with completed immune response bonding were then fixed on the surface of the sensor by an external magnetic field. Therefore, the measured object can directly contact the sensor surface, and quantitative detection of the protein concentration can be achieved. Apolipoprotein A1 (APOA1) was detected as a target protein, with a minimum detection limit of approximately 12.5 ng/mL. PMID- 26553102 TI - Synthesis of multi-functional materials through self-assembly of N-alkyl phenothiazine linked poly(aryl ether) dendrons. AB - Multi-functional self-assembled systems are developed from first and second generation poly aryl ether dendrons, which are covalently attached to N-alkyl phenothiazine unit through an acylhydrazone linkage. For the first time, dendron based systems have been utilized for efficient oil spill recovery. Furthermore, the hydrophobic nature of the compound has been exploited to make self-cleaning surfaces with anti-wetting properties. More importantly, the visco-elastic property of the gel enables us to develop a gel based ink from the compound, which can be read under UV-light. PMID- 26553101 TI - Retention of basic life support knowledge, self-efficacy and chest compression performance in Thai undergraduate nursing students. AB - This study explored the retention of basic life support knowledge, self-efficacy, and chest compression performance among Thai nursing students at a university in Thailand. A one-group, pre-test and post-test design time series was used. Participants were 30 nursing students undertaking basic life support training as a care provider. Repeated measure analysis of variance was used to test the retention of knowledge and self-efficacy between pre-test, immediate post-test, and re-test after 3 months. A Wilcoxon signed-rank test was used to compare the difference in chest compression performance two times. Basic life support knowledge was measured using the Basic Life Support Standard Test for Cognitive Knowledge. Self-efficacy was measured using the Basic Life Support Self-Efficacy Questionnaire. Chest compression performance was evaluated using a data printout from Resusci Anne and Laerdal skillmeter within two cycles. The training had an immediate significant effect on the knowledge, self-efficacy, and skill of chest compression; however, the knowledge and self-efficacy significantly declined after post-training for 3 months. Chest compression performance after training for 3 months was positively retaining compared to the first post-test but was not significant. Therefore, a retraining program to maintain knowledge and self efficacy for a longer period of time should be established after post-training for 3 months. PMID- 26553103 TI - Change in Cognitive Abilities in Older Latinos. AB - The aim of this study was to compare patterns of cognitive decline in older Latinos and non-Latinos. At annual intervals for a mean of 5.7 years, older Latino (n=104) and non-Latino (n=104) persons of equivalent age, education, and race completed a battery of 17 cognitive tests from which previously established composite measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. In analyses adjusted for age, sex, and education, performance declined over time in each cognitive domain, but there were no ethnic group differences in initial level of function or annual rate of decline. There was evidence of retest learning following the baseline evaluation, but neither the magnitude nor duration of the effect was related to Latino ethnicity, and eliminating the first two evaluations, during which much of retest learning occurred, did not affect ethnic group comparisons. Compared to the non-Latino group, the Latino group had more diabetes (38.5% vs. 25.0; chi2[1]=4.4; p=.037), fewer histories of smoking (24.0% vs. 39.4%, chi2[1]=5.7; p=.017), and lower childhood household socioeconomic level (-0.410 vs. -0.045, t[185.0]=3.1; p=.002), but controlling for these factors did not affect results. Trajectories of cognitive aging in different abilities are similar in Latino and non-Latino individuals of equivalent age, education, and race. (JINS, 2016, 22, 58-65). PMID- 26553104 TI - Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts. AB - PURPOSE: Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia. METHODS: We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities. RESULTS: Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1alpha. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment. CONCLUSIONS: In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients. PMID- 26553105 TI - The effect of annular repair on the failure strength of the porcine lumbar disc after needle puncture and punch injury. AB - PURPOSE: The purpose was to quantify the structural integrity of annulus fibrosis (AF) after injuries with repair. METHODS: Punctures in the AF of 6-month-old porcine spine specimens were made with 18-, 20-, 22-, 24-, and 26-gauge needles. Leakage testing was performed immediately after needle puncture (Group 1), after the puncture was repaired with a modified purse-string suture (MPSS) (Group 2), and after needle puncture with immediate repair (Group 3). Punch injuries repaired with the MPSS alone, or with an AF graft and MPSS were also examined. RESULTS: There was no leakage from 26-gauge needle punctures. Pressures at which the nucleus pulposus leaked from the 24-, 22-, 20- and 18-gauge needle punctures (Group 1) were 4.28, 2.03, 1.27, and 1.06 MPa, respectively. Failure pressure after repair (Group 2, 3) was significantly greater than without (Group 1). Failure pressure in Group 3 was much greater than in Group 2 with 18- and 20 gauge punctures. Punch injury repaired with a graft and MPSS had significantly greater failure pressure than repair with MPSS alone (1.88 vs. 1.02 MPa, p = 0.0001). CONCLUSIONS: The MPSS can restore the mechanical integrity of the AF after needle puncture. An annular graft along with a MPSS may increase the structural integrity of the AF after a punch injury. As this was an acute animal study, the measurements and results may not directly translate to the human intervertebral disc. PMID- 26553106 TI - A randomized controlled trial of Mindfulness-Based Cognitive Therapy (MBCT) versus treatment-as-usual (TAU) for chronic, treatment-resistant depression: study protocol. AB - BACKGROUND: Major depression is a common psychiatric disorder, frequently taking a chronic course. Despite provision of evidence-based treatments, including antidepressant medication and psychological treatments like cognitive behavioral therapy or interpersonal therapy, a substantial amount of patients do not recover. Mindfulness-Based Cognitive Therapy (MBCT) has been found to be effective in reducing relapse in recurrent depression, as well as lowering symptom levels in acute depression. The effectiveness of MBCT for chronic, treatment-resistant depression has only be studied in a few pilot trials. A large randomized controlled trial is necessary to examine the effectiveness of MBCT in reducing depressive symptoms in chronic, treatment-resistant depression. METHODS/DESIGN: A randomized-controlled trial is conducted to compare MBCT with treatment-as-usual (TAU). Patients with chronic, treatment-resistant depression who have received antidepressant medication and cognitive behavioral therapy or interpersonal therapy are included. Assessments take place at baseline and post intervention/TAU-period. The primary outcome are depressive symptoms. Secondary outcomes are: remission rates, quality of life, rumination, mindfulness skills and self-compassion. Patients in the TAU condition are offered to participate in the MBCT after the post TAU-period assessment. From all completers of the MBCT (MBCT condition and patients participating after the TAU-period), follow-up assessments are taken at three and six months after the completion of the MBCT. DISCUSSION: This trial will result in valuable information about the effectiveness of MBCT in chronic, treatment-resistant depressed patients who previously received antidepressant medication and psychological treatment. TRIAL REGISTRATION: trialregister.nl NTR4843, registered 14th October 2014. PMID- 26553107 TI - AlignWise: a tool for identifying protein-coding sequence and correcting frame shifts. AB - BACKGROUND: Identifying protein-coding genes from species without a reference genome sequence can be complicated by the presence of sequencing errors, particularly insertions and deletions. A number of tools capable of correcting erroneous frame-shifts within assembled transcripts are available but often do not report back DNA sequences required for subsequent phylogenetic analysis. Amongst those that do, the Genewise algorithm is the most effective. However, it requires a homology wrapper to be used in this way, and here we demonstrate it perfectly corrects frame-shifts only 60% of the time. RESULTS: We therefore created AlignWise, a tool that combines Genewise with our own homology-based method, AlignFS, to identify protein-coding regions and correct erroneous frame shifts, suitable for subsequent phylogenetic analysis. We compared AlignWise against other open reading frame finding software and demonstrate that the AlignFS algorithm is more accurate than Genewise at correcting frame-shifts within an order. We show that AlignWise provides the greatest accuracy at higher evolutionary distances, out-performing both AlignFS and Genewise individually. CONCLUSIONS: AlignWise produces a single ORF per transcript and identifies and corrects frame-shifts with high accuracy. It is therefore well suited for analysing novel transcriptome assemblies and EST sequences in the absence of a reference genome. PMID- 26553108 TI - Effect of oxidative stress on ventricular repolarization in patients with type 2 diabetes: non-invasive quantification via transmural dispersion of repolarization. PMID- 26553109 TI - User Interaction in Semi-Automatic Segmentation of Organs at Risk: a Case Study in Radiotherapy. AB - Accurate segmentation of organs at risk is an important step in radiotherapy planning. Manual segmentation being a tedious procedure and prone to inter- and intra-observer variability, there is a growing interest in automated segmentation methods. However, automatic methods frequently fail to provide satisfactory result, and post-processing corrections are often needed. Semi-automatic segmentation methods are designed to overcome these problems by combining physicians' expertise and computers' potential. This study evaluates two semi automatic segmentation methods with different types of user interactions, named the "strokes" and the "contour", to provide insights into the role and impact of human-computer interaction. Two physicians participated in the experiment. In total, 42 case studies were carried out on five different types of organs at risk. For each case study, both the human-computer interaction process and quality of the segmentation results were measured subjectively and objectively. Furthermore, different measures of the process and the results were correlated. A total of 36 quantifiable and ten non-quantifiable correlations were identified for each type of interaction. Among those pairs of measures, 20 of the contour method and 22 of the strokes method were strongly or moderately correlated, either directly or inversely. Based on those correlated measures, it is concluded that: (1) in the design of semi-automatic segmentation methods, user interactions need to be less cognitively challenging; (2) based on the observed workflows and preferences of physicians, there is a need for flexibility in the interface design; (3) the correlated measures provide insights that can be used in improving user interaction design. PMID- 26553110 TI - High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation. AB - Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing (TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated. PMID- 26553111 TI - A cationic azobenzene-surfactant-modified graphene hybrid: unique photoresponse and electrochemical behavior. AB - Surfactant-modified graphene hybrids containing azobenzene groups were for the first time prepared, and the electrochemical performance was investigated. The hybrids were obtained by electrostatic interactions between cationic azobenzene surfactants and negatively charged graphene oxide in water. The electrostatic interactions, chemical structure and photoresponse of the hybrids were measured by using zeta potential values, fluorescence spectra, FTIR, XPS, XRD, SEM, UV-Vis absorption, AFM and Raman spectra. The electrochemical performance was estimated using cyclic voltammetry. The results show that strong electrostatic interactions exist between the azobenzene surfactants and graphene oxide. Notably, this azobenzene-graphene hybrid can self-assemble into aggregation structures in aqueous solution. Besides, the self-assembly can be reversibly controlled by ultraviolet light (365 nm) and blue light (455 nm) irradiation. This process is driven by the photoinduced polarity change of the cationic azobenzene surfactant and is responsible for the graphene hybrids' electrochemical performance. It is the first example of the reversible self-assembly of graphene driven by light irradiation. PMID- 26553112 TI - Pop in, pop out: a novel gene-targeting strategy for use with CRISPR-Cas9. AB - The CRISPR-Cas9 system is frequently used to create small deletions in the genomes of mammalian cells, but the isolation of precisely targeted mutants is still challenging. A new, two-step 'pop in & out' targeting approach facilitates this task. PMID- 26553113 TI - Absence of physiologic breast response to pregnancy and lactation after radiation therapy. PMID- 26553115 TI - Correction to "Synthetic metallochaperone ZMC1 rescues mutant p53 conformation by transporting zinc into cells as an ionophore". PMID- 26553114 TI - Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis. AB - Improving the quality of exposure-response modeling is important in clinical drug development. The general joint modeling of multiple endpoints is made possible in part by recent progress on the latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate, when modeling a continuous and a categorical clinical endpoint, the level of improvement achievable by joint modeling in the latent variable IDR modeling framework through the sharing of model parameters for the individual endpoints, guided by the appropriate representation of drug and placebo mechanism. This was illustrated with data from two phase III clinical trials of intravenously administered mAb X for the treatment of rheumatoid arthritis, with the 28-joint disease activity score (DAS28) and 20, 50, and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and ACR70) disease severity criteria were used as efficacy endpoints. The joint modeling framework led to a parsimonious final model with reasonable performance, evaluated by visual predictive check. The results showed that, compared with the more common approach of separately modeling the endpoints, it is possible for the joint model to be more parsimonious and yet better describe the individual endpoints. In particular, the joint model may better describe one endpoint through subject-specific random effects that would not have been estimable from data of this endpoint alone. PMID- 26553116 TI - Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease. AB - OBJECTIVES: Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. METHODS: Patients with CKD aged >= 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. RESULTS: A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (beta = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (beta = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. CONCLUSIONS: This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553117 TI - Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling. AB - BACKGROUND: The effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats. METHODS: Fifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography. RESULTS: Glycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05). CONCLUSIONS: Systolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores. PMID- 26553119 TI - Ascending aortic aneurysm caused by Mycobacterium tuberculosis. AB - BACKGROUND: Tuberculous aortitis is an unusual presentation of a common disease in Sri Lanka. There were no reported cases of tuberculous aortitis from Sri Lanka. Here we report a case of a 40-year-old woman who developed an ascending aortic aneurysm with severe aortic regurgitation caused by Mycobacterium tuberculosis. CASE PRESENTATION: A 40-year-old Sri Lankan female who presented with exertional breathlessness (NYHA II) and weight loss for 4 weeks duration was found to have collapsing pulse and early diastolic murmur at left sternal edge. Transthoracic and transesophageal echocardiogram showed ascending aortic aneurysm with severe aortic regurgitation. Computed tomographic aortography confirmed the diagnosis of aneurysmal dilatation of the ascending aorta. She underwent successful aortic valve replacement and aortic root replacement. The final diagnosis of tuberculous aortitis was made on the basis of macroscopic appearance of inflammation and microscopic confirmation of caseating granuloma. She made a good clinical recovery with category 1 antituberculous chemotherapy. CONCLUSIONS: Although most cases of aortitis are non-infectious in Sri Lanka, an infectious etiology must be considered in the differential diagnosis because therapeutic approaches differ widely. Tuberculous aortitis may be under diagnosed in Sri Lanka, a country with intermediate tuberculosis burden, as the histological or microbiological diagnosis is not possible in most cases. The clinical and radiological diagnostic criteria for tuberculous aortitis need to be set out in case of aneurysmal aortic disease in the absence of apparent etiology. PMID- 26553118 TI - Cross-Sectional Study of Respiratory Symptoms, Spirometry, and Immunologic Sensitivity in Epoxy Resin Workers. AB - OBJECTIVES: An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers. METHODS: Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products. RESULTS: We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23-infinity], p = 0.030) or wheeze (OR 4.44, [1.00 22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86-589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers. CONCLUSIONS: In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization. PMID- 26553120 TI - Gravity-driven postseismic deformation following the Mw 6.3 2009 L'Aquila (Italy) earthquake. AB - The present work focuses on the postseismic deformation observed in the region of L'Aquila (central Italy) following the Mw 6.3 earthquake that occurred on April 6, 2009. A new, 16-month-long dataset of COSMO-SkyMed SAR images was analysed using the Persistent Scatterer Pairs interferometric technique. The analysis revealed the existence of postseismic ground subsidence in the mountainous rocky area of Mt Ocre ridge, contiguous to the sedimentary plain that experienced coseismic subsidence. The postseismic subsidence was characterized by displacements of 10 to 35 mm along the SAR line of sight. In the Mt Ocre ridge, widespread morphological elements associated with gravitational spreading have been previously mapped. We tested the hypothesis that the postseismic subsidence of the Mt Ocre ridge compensates the loss of equilibrium induced by the nearby coseismic subsidence. Therefore, we simulated the coseismic and postseismic displacement fields via the finite element method. We included the gravitational load and fault slip and accounted for the geometrical and rheological characteristics of the area. We found that the elastoplastic behaviour of the material under gravitational loading best explains the observed postseismic displacement. These findings emphasize the role of gravity in the postseismic processes at the fault scale. PMID- 26553122 TI - Should we keep on measuring multimorbidity? PMID- 26553123 TI - [Securing the therapy management during the leave permissions for the elderly patients]. AB - Leave permission can be granted over a limited period of hospitalisation during which the patient can return home under the responsibility of the hospital. Despite its frequency, this practice is not evaluated in terms of maintaining the security of medication. This complex process involves several actors, processes and locations. In that case, the drug iatrogenic risk is not at all negligible, especially for the elderly. Patient comprehension of medication is not always easy and must be evaluated before leaving the hospital. Therefore, a risk analysis has been initiated to ensure the medical practice's security of our geriatric hospital. Multidisciplinary working group meetings were dedicated to analyse and overcome 21 unacceptable failure modes. The establishment of traceability nurse/patient for the medication intake, information and evaluation of drug monitoring allowed the patient's medication compliance. In the meanwhile, the role of the working group on the security of the internal drug circuit in the hospital has integrated the harmonization of practices, a unique source of information and a variety of comprehensible, readable and informative materials to propose to the patients. These preventive actions have been formulated to secure, optimize and to individualize drug management during the leave permission. In the context of optimization during transit period home/hospital, this process reorganized by the working group can be integrated in a public health approach to reduce the number of preventable readmissions. PMID- 26553124 TI - Vitiligo and remarkable freckles in chronic graft-versus-host disease. PMID- 26553125 TI - Anti-inflammatory effects of Saururus chinensis aerial parts in murine macrophages via induction of heme oxygenase-1. AB - Saururus chinensis (Lour.) Baill. is a perennial plant distributed throughout Northeast Asia and its roots have been widely used as a traditional medicine for hepatitis, asthma, pneumonia, and gonorrhea. This study was designed to investigate the anti-inflammatory activity of an extract of S. chinensis of the aerial parts (rather than the root), and the signaling pathway responsible for this effect in lipopolysaccharide-stimulated murine macrophages. The subfraction 4 (SCF4) from the n-hexane layer of the ethanol extract of the aerial parts of S. chinensis exhibited the highest nitrite-inhibitory activity. SCF4 significantly inhibited the production of nitrite and the expression of pro-inflammatory mediators via heme oxygenase-1 upregulation. SCF4 caused significant phosphorylation of p38 MAPK and Akt, which subsequently induced the nuclear translocation of p-p65 nuclear factor-kappaB and Nrf2. SCF4 also suppressed the phosphorylation of signal transducers and activators of transcription 1 (p STAT1). The heme oxygenase-1 inhibitor zinc protoporphyrin attenuated the inhibitory effect of SCF4 on lipopolysaccharide-stimulated nitrite production and expression of inflammatory mediators, tumor necrosis factor alpha, and p-STAT1. We identified sauchinone as the active compound in S. chinensis extract and SCF4. Sauchinone was shown to significantly inhibit nitrite production and inflammatory mediators expression via heme oxygenase-1 upregulation. These results suggest that S. chinensis extract, SCF4, and its active compound, sauchinone, could be used as an anti-inflammatory agent. PMID- 26553121 TI - Hyponatremia in the intensive care unit: How to avoid a Zugzwang situation? AB - Hyponatremia is a common electrolyte derangement in the setting of the intensive care unit. Life-threatening neurological complications may arise not only in case of a severe (<120 mmol/L) and acute fall of plasma sodium levels, but may also stem from overly rapid correction of hyponatremia. Additionally, even mild hyponatremia carries a poor short-term and long-term prognosis across a wide range of conditions. Its multifaceted and intricate physiopathology may seem deterring at first glance, yet a careful multi-step diagnostic approach may easily unravel the underlying mechanisms and enable physicians to adopt the adequate measures at the patient's bedside. Unless hyponatremia is associated with obvious extracellular fluid volume increase such as in heart failure or cirrhosis, hypertonic saline therapy is the cornerstone of the therapeutic of profound or severely symptomatic hyponatremia. When overcorrection of hyponatremia occurs, recent data indicate that re-lowering of plasma sodium levels through the infusion of hypotonic fluids and the cautious use of desmopressin acetate represent a reasonable strategy. New therapeutic options have recently emerged, foremost among these being vaptans, but their use in the setting of the intensive care unit remains to be clarified. PMID- 26553126 TI - Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt-sensitive rats. AB - Renalase is currently the only known amine oxidase in the blood that can metabolize catecholamines and regulate sympathetic activity. High salt intake is associated with high blood pressure (BP), possibly through the modulation of renalase expression and secretion, whereas potassium can reverse the high salt mediated increase in blood pressure. However, whether potassium could also modulate BP through renalase is unclear. In this study, we aim to investigate how salt intake and potassium supplementation affect the level of renalase in rats. Eighteen salt-sensitive (SS) and 18 SS-13BN rats were divided into six groups, receiving normal salt (0.3% NaCl), high salt (8% NaCl) and high salt/potassium (8% NaCl and 8% KCl) dietary intervention for four weeks. At the end of experiments, blood and kidneys were collected for analysis. mRNA level of renalase was measured by quantitative real-time PCR and protein level was determined by Western blot. We found that mRNA and protein levels of renalase in the kidneys of SS and SS-13BN rats were significantly decreased (P < 0.05) after high salt intervention, whereas dopamine in plasma was increased (P < 0.05) compared with rats received normal salt, suggesting that salt may induce salt sensitive hypertension through inhibition of renalase expression. We also found increased mRNA level and protein level of renalase, decreased catecholamine levels in plasma, and decreased BP in SS rats treated with high salt/potassium, compared with that of the high salt SS group. Taken together, the salt-induced increase and potassium-induced decrease in BP could be mediated through renalase. More studies are needed to confirm our findings and understand the underlying mechanisms. PMID- 26553127 TI - A Holistic Multi Evidence Approach to Study the Fragmentation Behaviour of Crystalline Mannitol. AB - Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the beta-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties. PMID- 26553128 TI - A single cervical length measurement at 18-24 weeks is a better predictor of preterm birth than the change in cervical length with gestation. PMID- 26553130 TI - Nanotechnology in Phytotherapy: Antiinflammatory Effect of a Nanostructured Thymol Gel from Lippia sidoides in Acute Periodontitis in Rats. AB - Lippia sidoides Cham (Verbenaceae) is largely distributed in the northeastern region of Brazil. It is popularly known as 'Alecrim-pimenta'. Recent studies have shown that some species of Lippia have interesting pharmacological activities. This study aimed to evaluate the effect of a nanostructured thymol gel (TG) 1.2 mg/g on acute phase of ligature-induced periodontitis model [acute periodontal disease (APD)] in rats. APD was induced in 24 Wistar rats subjected to ligature placement on left molars in maxillae. Animals were treated with TG, immediately after APD induction. Saline-based gel was utilized as negative control and diethylammonium diclofenac gel 10 mg/g was used as positive control. Animals were randomly assigned into the groups. The periodontium and the surrounding gingiva were examined at histopathology, as well as the neutrophil influx into the gingiva was assayed using myeloperoxidase activity levels by ELISA method. TG treatment reduced tissue lesion at histopathology coupled to decreased myeloperoxidase activity production in gingival tissue when compared with the saline gel control group (p < 0.05). The TG gel was able to provide a significant myeloperoxidase decreasing in gingiva tissue confirming to be effective in reducing gingival inflammation in this model. PMID- 26553131 TI - Atom-Economical Dimerization Strategy by the Rhodium-Catalyzed Addition of Carboxylic Acids to Allenes: Protecting-Group-Free Synthesis of Clavosolide A and Late-Stage Modification. AB - Natural products of polyketide origin with a high level of symmetry, in particular C2 -symmetric diolides as a special macrolactone-based product class, often possess a broad spectrum of biological activity. An efficient route to this important structural motif was developed as part of a concise and highly convergent synthesis of clavosolide A. This strategy features an atom-economic "head-to-tail" dimerization by the stereoselective rhodium-catalyzed addition of carboxylic acids to terminal allenes with the simultaneous construction of two new stereocenters. The excellent efficiency and selectivity with which the C2 symmetric core structures were obtained are remarkable considering the outcome under classical dimerization conditions. Furthermore, this approach facilitates late-stage modification and provides ready access to potential new lead structures. PMID- 26553129 TI - A systematic review of instruments for measuring outcomes in economic evaluation within aged care. AB - BACKGROUND: This paper describes the methods and results of a systematic review to identify instruments used to measure quality of life outcomes in older people. The primary focus of the review was to identify instruments suitable for application with older people within economic evaluations conducted in the aged care sector. METHODS: Online databases searched were PubMed, Medline, Scopus, and Web of Science, PsycInfo, CINAHL, Embase and Informit. Studies that met the following criteria were included: 1) study population exclusively above 65 years of age 2) measured health status, health related quality of life or quality of life outcomes more broadly through use of an instrument developed for this purpose, 3) used a generic preference based instrument or an older person specific preference based or non-preference based instrument or both, and 4) published in journals in the English language after 2000. RESULTS: The most commonly applied generic preference based instrument in both the community and residential aged care context was the EuroQol - 5 Dimensions (EQ-5D), followed by the Adult Social Care Outcomes Toolkit (ASCOT) and the Health Utilities Index (HUI2/3). The most widely applied older person specific instrument was the ICEpop CAPability measure for Older people (ICECAP-O) in both community and residential aged care. CONCLUSION: In the absence of an ideal instrument for incorporating into economic evaluations in the aged care sector, this review recommends the use of a generic preference based measure of health related quality of life such as the EQ-5D to obtain quality adjusted life years, in combination with an instrument that has a broader quality of life focus like the ASCOT, which was designed specifically for evaluating interventions in social care or the ICECAP O, a capability measure for older people. PMID- 26553132 TI - miR-23a binds to p53 and enhances its association with miR-128 promoter. AB - Apoptosis plays an important role in cardiac pathology, but the molecular mechanism by which apoptosis regulated remains largely elusive. Here, we report that miR-23a promotes the apoptotic effect of p53 in cardiomyocytes. Our results showed that miR-23a promotes apoptosis induced by oxidative stress. In exploring the molecular mechanism by which miR-23a promotes apoptosis, we found that it sensitized the effect of p53 on miR-128 regulation. It promoted the association of p53 to the promoter region of miR-128, and enhanced the transcriptional activation of p53 on miR-128 expression. miR-128 can downregulate prohibitin expression, and subsequently promote apoptosis. Our data provides novel evidence revealing that miR-23a can stimulate transcriptional activity of p53. PMID- 26553133 TI - Thyroid function: Differentiated pluripotent stem cells restore thyroid function. PMID- 26553135 TI - Sample size considerations for the external validation of a multivariable prognostic model: a resampling study. AB - After developing a prognostic model, it is essential to evaluate the performance of the model in samples independent from those used to develop the model, which is often referred to as external validation. However, despite its importance, very little is known about the sample size requirements for conducting an external validation. Using a large real data set and resampling methods, we investigate the impact of sample size on the performance of six published prognostic models. Focussing on unbiased and precise estimation of performance measures (e.g. the c-index, D statistic and calibration), we provide guidance on sample size for investigators designing an external validation study. Our study suggests that externally validating a prognostic model requires a minimum of 100 events and ideally 200 (or more) events. PMID- 26553134 TI - Regulation of metabolism by the innate immune system. AB - Low-grade tissue inflammation induced by obesity can result in insulin resistance, which in turn is a key cause of type 2 diabetes mellitus. Cells of the innate immune system produce cytokines and other factors that impair insulin signalling, which contributes to the connection between obesity and the onset of type 2 diabetes mellitus. Here, we review the innate immune cells involved in secreting inflammatory factors in the obese state. In the adipose tissue, these cells include proinflammatory adipose tissue macrophages and natural killer cells. We also discuss the role of innate immune cells, such as anti-inflammatory adipose tissue macrophages, eosinophils, group 2 innate lymphoid cells and invariant natural killer T cells, in maintaining an anti-inflammatory and insulin sensitive environment in the lean state. In the liver, both Kupffer cells and recruited hepatic macrophages can contribute to decreased hepatic insulin sensitivity. Proinflammatory macrophages might also adversely affect insulin sensitivity in the skeletal muscle and pancreatic beta-cell function. Finally, this Review provides an overview of the mechanisms for regulating proinflammatory immune responses that could lead to future therapeutic opportunities to improve insulin sensitivity. PMID- 26553136 TI - Genomic profiling of CHEK2*1100delC-mutated breast carcinomas. AB - BACKGROUND: CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. METHODS: We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. RESULTS: High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, these samples mostly have very few copy number aberrations and no detectable regions of LOH. By unsupervised hierarchical clustering of copy number data we observed a great degree of heterogeneity amongst the CHEK2*1100delC breast cancers, comparable to the BRCAX breast cancers. Furthermore, copy number aberrations were mostly seen at low frequencies in both the CHEK2*1100delC and BRCAX group of breast cancers. However, supervised class comparison identified copy number loss of chromosomal arm 1p to be associated with CHEK2*1100delC status. CONCLUSIONS: In conclusion, in contrast to basal-like BRCA1 mutated breast cancers, no apparent specific somatic copy number aberration (CNA) profile for CHEK2*1100delC breast cancers was found. With the possible exception of copy number loss of chromosomal arm 1p in a subset of tumors, which might be involved in CHEK2 tumorigenesis. This difference in CNAs profiles might be explained by the need for BRCA1-deficient tumor cells to acquire survival factors, by for example specific copy number aberrations, to expand. Such factors may not be needed for breast tumors with a defect in a non-essential gene such as CHEK2. PMID- 26553137 TI - Association between genetic variants of the clock gene and obesity and sleep duration. AB - Obesity is a multifactorial disease caused by the interaction of genetic and environmental factors related to lifestyle aspects. It has been shown that reduced sleep is associated with increased body mass index (BMI). Circadian Locomotor Output Cycles Kaput (CLOCK) gene variants have also been associated with obesity. The objective of this mini-review was to discuss the available literature related to CLOCK gene variants associated with adiposity and sleep duration in humans. In total, 16 articles complied with the terms of the search that reported CLOCK variants associated with sleep duration, energy intake, and BMI. Overall, six CLOCK single nucleotide polymorphisms (SNPs) have been associated with sleep duration, and three variants have been associated with energy intake variables. Overall, the most studied area has been the association of CLOCK gene with obesity; close to eight common variants have been associated with obesity. The most studied CLOCK SNP in different populations is rs1801260, and most of these populations correspond to European populations. Collectively, identifying at risk CLOCK genotypes is a new area of research that may help identify individuals who are more susceptible to overeating and gaining weight when exposed to short sleep durations. PMID- 26553138 TI - Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells. AB - BACKGROUND: Our previous data demonstrated that targeting non-homologous end joining repair (NHEJR) yields a higher radiosensitivity than targeting homologous recombination repair (HRR) to heavy ions using DNA repair gene knockouts (KO) in mouse embryonic fibroblast (MEF). In this study, we determined if combining the use of an NHEJR inhibitor with carbon (C) ion irradiation was more efficient in killing human cancer cells compared with only targeting a HRR inhibitor. METHODS: The TP53-null human non-small cell lung cancer cell line H1299 was used for testing the radiosensitizing effect of NHEJR-related DNA-dependent protein kinase (DNA-PK) inhibitor NU7026, HRR-related Rad51 inhibitor B02, or both to C ion irradiation using colony forming assays. The mechanism underlying the inhibitor radiosensitization was determined by flow cytometry after H2AX phosphorylation staining. HRR-related Rad54-KO, NHEJR-related Lig4-KO, and wild-type TP53-KO MEF were also included to confirm the suppressing effect specificity of these inhibitors. RESULTS: NU7026 showed significant sensitizing effect to C ion irradiation in a concentration-dependent manner. In contrast, B02 showed a slight sensitizing effect to C ion irradiation. The addition of NU7026 significantly increased H2AX phosphorylation after C ion and x-ray irradiations in H1299 cells, but not B02. NU7026 had no effect on radiosensitivity to Lig4-KO MEF and B02 had no effect on radiosensitivity to Rad54-KO MEF in both irradiations. CONCLUSION: These results suggest that inhibitors targeting the NHEJR pathway could significantly enhance radiosensitivity of human cancer cells to C ion irradiation, rather than targeting the HRR pathway. PMID- 26553140 TI - Policy Barriers to Best Practices: The Impact of Restrictive State Regulations on Access to Long-acting Reversible Contraceptives. PMID- 26553139 TI - Fatalism, medical mistrust, and pretreatment health-related quality of life in ethnically diverse prostate cancer patients. AB - OBJECTIVE: Few studies have examined the impact of cultural processes prevalent in minority ethnic groups such as cancer fatalism and medical mistrust on health related quality of life (HRQoL) following a cancer diagnosis. The present study examined relationships among ethnicity, HRQoL, and two possible cultural vulnerability factors-fatalistic attitudes and medical mistrust-among an ethnically diverse sample of men with prostate cancer (PC) prior to undergoing active treatment. METHODS: A total of 268 men with localized PC (30% African American, 29% Hispanic, and 41% non-Hispanic White) were assessed cross sectionally prior to active treatment. Path analyses examined relationships among ethnicity, vulnerability factors, and HRQoL. RESULTS: Ethnicity was not related to HRQoL after controlling for relevant covariates. Hispanic men reported greater cancer fatalism compared with non-Hispanic White men (beta = 0.15, p = 0.03), and both Hispanics (beta = 0.19, p < 0.01) and African Americans (beta = 0.20, p < 0.01) reported greater medical mistrust than non-Hispanic Whites. Fatalism demonstrated a trend toward negatively impacting physical well-being (beta = 0.12, p = 0.06), but was not significantly related to emotional well-being (beta = -0.10, p = 0.11). Greater medical mistrust was associated with poorer physical (beta = -0.14, p = 0.03) and emotional well-being (beta = -0.13, p = 0.04). CONCLUSIONS: Results indicate that fatalistic attitudes and medical system mistrust were more prevalent among minority men. Less trust in the medical system was associated with poorer physical and emotional well-being. Attention to perceptions of the healthcare system and its relation to HRQoL may have implications for targeting culturally driven attitudes that may compromise adjustment to a PC diagnosis.Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553141 TI - Radical fluorination powered expedient synthesis of 3-fluorobicyclo[1.1.1]pentan 1-amine. AB - Exploration of novel chemical space, a modern trend in medicinal chemistry, is heavily reliant on synthetic access to new and interesting building blocks. In this direction, the following work describes an expedient synthesis of one such moiety, 3-fluorobicyclo[1.1.1]pentan-1-amine, by employing radical fluorination. PMID- 26553142 TI - Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: prospective, multicentre cohort study. AB - STUDY QUESTION: What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non traumatic intracerebral haemorrhage? METHODS: This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. STUDY ANSWER AND LIMITATIONS: A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced permanent sequelae. Not all patients with negative CT angiography and MRI/MRA results underwent DSA. Although the previous probability of finding a macrovascular cause was lower in patients who did not undergo DSA, some small arteriovenous malformations or dural arteriovenous fistulas may have been missed. WHAT THIS STUDY ADDS: CT angiography is an appropriate initial investigation to detect macrovascular causes of non-traumatic intracerebral haemorrhage, but accuracy is modest. Additional MRI/MRA may find cavernomas or alternative diagnoses, but DSA is needed to diagnose macrovascular causes undetected by CT angiography or MRI/MRA. FUNDING, COMPETING INTERESTS, DATA SHARING: Dutch Heart Foundation and The Netherlands Organisation for Health Research and Development, ZonMw. The authors have no competing interests. Direct requests for additional data to the corresponding author. PMID- 26553143 TI - Appropriate antibiotic use for patients with complicated urinary tract infections in 38 Dutch Hospital Departments: a retrospective study of variation and determinants. AB - BACKGROUND: Appropriate antibiotic use in patients with complicated urinary tract infections can be measured by a valid set of nine quality indicators (QIs). We evaluated the performance of these QIs in a national setting and investigated which determinants influenced appropriate antibiotic use. For the latter, we distinguished patient, department and hospital characteristics, including organizational interventions aimed at improving the quality of antibiotic use (antibiotic stewardship elements). METHODS: A retrospective, observational multicentre study included 1964 patients (58% male sex) with a complicated urinary tract infection treated at Internal Medicine and Urology departments of 19 Dutch university and non-university hospitals. Data of 50 patients per department were extracted from medical charts. QI performance scores were calculated using previously constructed algorithms. Department and hospital characteristics were collected using questionnaires filled in by an internal medicine physician and an urologist. Regression analysis was performed to identify determinants of QI performance. Clustering at department and hospital level was taken into account through inclusion of random effects in a multi-level model. RESULTS: Median QI performance of departments varied between 31% ('Treat urinary tract infection in men according to local guideline') and 77% ('Perform urine culture'). The patient characteristics non-febrile urinary tract infection, female sex and presence of a urinary catheter were negatively associated with performance on many QIs. The presence of an infectious diseases physician and an antibiotic formulary were positively associated with 'Prescribe empirical therapy according to guideline'. No other department or hospital characteristics, including stewardship elements, were consistently associated with better QI performance. CONCLUSIONS: A large inter-department variation was demonstrated in the appropriateness of antibiotic use. In particular certain patient characteristics (more than department or hospital characteristics) influenced the quality of antibiotic use. Some, but not all antibiotic stewardship elements did translate into better QI performance. PMID- 26553144 TI - Internet screening for anxiety disorders: Treatment-seeking outcomes in a three month follow-up study. AB - Although many people use the internet to diagnose mental health problems, little is known about the relationship between internet self-diagnosis and treatment seeking. The MACSCREEN (a validated, self-report screening tool for anxiety and depression) was posted on our clinic homepage and respondents were invited to take an anxiety test. Three months after completing the MACSREEN and a variety of symptom severity scales, respondents were emailed a follow up questionnaire asking about treatment-seeking behaviours. Of the 770 MACSCREEN respondents, 103 completed the follow-up questionnaire. Of these, 100% met criteria for at least one anxiety or mood disorder diagnosis and 51% sought treatment after completing the MACSCREEN. In the 49% who did not seek treatment, fear of medication (57%), discomfort talking to their doctor about anxiety (28%) and the belief that symptoms were not severe enough (28%) were cited as barriers. Compared to non seekers, treatment-seekers were significantly more likely to meet screening criteria for Generalized Anxiety Disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder and Depression. Higher Sheehan Disability Scale scores and being married (versus single) significantly increased the odds of treatment-seeking, suggesting that functional impairment and disease burden on the family may be stronger predictors of treatment seeking than overall severity of symptoms. PMID- 26553145 TI - Stigma never dies: Mourning a spouse who died of AIDS in China. AB - Stigma towards people with HIV (PHIV) can affect their family members. In this study of 68 HIV seronegative participants in China whose spouse died of AIDS, 35.3% reported prolonged grief. Stigma beliefs towards PHIV (i.e., belief that PHIV's death leaves the deceased, the family and society better off) predicted grief symptoms. Social campaigns to combat stigma and grief therapy to reconstruct the meaning of HIV-related death may be helpful to reduce suffering in HIV bereaved. PMID- 26553146 TI - Skidmore Clips of Neutral and Expressive Scenarios (SCENES): Novel dynamic stimuli for social cognition research. AB - Social cognition research has relied primarily on photographic emotional stimuli. Such stimuli likely have limited ecological validity in terms of representing real world social interactions. The current study presents evidence for the validity of a new stimuli set of dynamic social SCENES (Skidmore Clips of Emotional and Neutral Expressive Scenarios). To develop these stimuli, ten undergraduate theater students were recruited to portray members of an audience. This audience was configured to display (seven) varying configurations of social feedback, ranging from unequivocally approving to unequivocally disapproving (including three different versions of balanced/neutral scenes). Validity data were obtained from 383 adult participants recruited from Amazon's Mechanical Turk. Each participant viewed three randomly assigned scenes and provided a rating of the perceived criticalness of each scene. Results indicate that the SCENES reflect the intended range of emotionality, and pairwise comparisons suggest that the SCENES capture distinct levels of critical feedback. Overall, the SCENES stimuli set represents a publicly available (www.scenesstimuli.com) resource for researchers interested in measuring social cognition in the presence of dynamic and naturalistic social stimuli. PMID- 26553148 TI - Toward a unifying strategy for the structure-based prediction of toxicological endpoints. AB - Most computational methods used for the prediction of toxicity endpoints are based on the assumption that similar compounds have similar biological properties. This principle can be exploited using computational methods like read across or quantitative structure-activity relationships. However, there is no general agreement about which method is the most appropriate for quantifying compound similarity neither for exploiting the similarity principle in order to obtain reliable estimations of the compound properties. Moreover, optimal similarity metrics and modeling methods might depend on the characteristics of the endpoints and training series used in each case. This study describes a comparative analysis of the predictive performance of diverse similarity metrics and modeling methods in toxicological applications. A collection of two quantitative (n = 660, n = 1114) and three qualitative (n = 447, n = 905, n = 1220) datasets representing very different endpoints of interest in drug safety evaluation and rigorous methods were used to estimate the external predictive ability in each case. The results confirm that no single approach produces the best results in all instances, and the best predictions were obtained using different tools in different situations. The trends observed in this study were exploited to propose a unifying strategy allowing the use of the most suitable method for every compound. A comparison of the quality of the predictions obtained by the unifying strategy with those obtained by standard prediction methods confirmed the usefulness of the proposed approach. PMID- 26553147 TI - Creation and validation of the Cognitive and Behavioral Response to Stress Scale in a depression trial. AB - The Cognitive and Behavioral Response to Stress Scale (CB-RSS) is a self-report measure of the use and helpfulness of several cognitive and behavioral skills. Unlike other measures that focus on language specific to terms used in therapy, the CB-RSS was intended to tap the strategies in ways that might be understandable to those who had not undergone therapy. The measure was included in a clinical trial of cognitive-behavioral therapy for depression and completed by 325 participants at baseline and end of treatment (18 weeks). Psychometric properties of the scale were assessed through iterative exploratory and confirmatory factor analyses. These analyses identified two subscales, cognitive and behavioral skills, each with high reliability. Validity was addressed by investigating relationships with depression symptoms, positive affect, perceived stress, and coping self-efficacy. End of treatment scores predicted changes in all outcomes, with the largest relationships between baseline CB-RSS scales and coping self-efficacy. These findings suggest that the CB-RSS is a useful tool to measure cognitive and behavioral skills both at baseline (prior to treatment) as well as during the course of treatment. PMID- 26553149 TI - Immunosuppressive phenolic compounds from Hydnora abyssinica A. Braun. AB - BACKGROUND: Hydnora abyssinica (HA) A. Braun is an endemic Sudanese medicinal plant traditionally used as anti-inflammatory and against many infectious diseases. However, it proved to be very rich in phenols and tannins, so the present study was undertaken to investigate the immunomodulatory potential of the whole plant ethanolic extract and its isolated compounds. METHODS: Lymphocyte proliferation, chemiluminescence and superoxide reduction assays were used for immunomodulatory evaluation. While, MTT (3-(4, 5-dimethylthazol-2-yl)-2, 5 diphenyl tetrazonium bromide) test was performed on 3 T3 cell line clone in order to evaluate the cytoxicity effect of the extracts and isolated compounds of phenolic derivatives which were carried out by chromotographic techniques. RESULTS: Catechin, (1), tyrosol (2) and benzoic acid, 3, 4, dihydroxy-, ethyl ester (3) compounds were isolated from HA ethanolic extract which revealed potent immunosuppressive activity against reactive oxygen species from both polymorph nuclear cells (PMNs) (45-90 % inhibition) and mononuclear cells (MNCs) (30 -65 % inhibition), T lymphocyte proliferation assay (70-93 % inhibition) as well as potent inhibitory effect against superoxide production (42-71 % inhibition) at concentrations of 6.25-100 MUg/mL. Catechin (1) was found the most potent immunosuppressive agent among all constituents examined. CONCLUSION: These results can support the traditional uses of H. abyssinica extracts as anti inflammatory and immunosuppressive and further investigations of the mode of action and other pharmacological studies are highly desirable. PMID- 26553150 TI - An interaction proteomics survey of transcription factor binding at recurrent TERT promoter mutations. AB - Aberrant telomerase reactivation in differentiated cells represents a major event in oncogenic transformation. Recurrent somatic mutations in the human telomerase reverse transcriptase (TERT) promoter region, predominantly localized to two nucleotide positions, are highly prevalent in many cancer types. Both mutations create novel consensus E26 transformation-specific (ETS) motifs and are associated with increased TERT expression. Here, we perform an unbiased proteome wide survey of transcription factor binding at TERT promoter mutations in melanoma. We observe ELF1 binding at both mutations in vitro and we show that increased recruitment of GABP is enabled by the spatial architecture of native and novel ETS motifs in the TERT promoter region. We characterize the dynamics of competitive binding between ELF1 and GABP and provide evidence for ELF1 exclusion by transcriptionally active GABP. This study thus provides an important description of proteome-wide, mutation-specific binding at the recurrent, oncogenic TERT promoter mutations. PMID- 26553151 TI - Sclerostin Enhances Adipocyte Differentiation in 3T3-L1 Cells. AB - Sclerostin, a secreted protein encoded by the Sost gene, is produced by osteocytes and is inhibited by osteoblast differentiation and bone formation. Recently, a functional association between bone and fat tissue has been suggested, and a correlation between circulating sclerostin levels and lipid metabolism has been reported in humans. However, the effects of sclerostin on adipogenesis remain unexplored. In the present study, we examined the role of sclerostin in regulating adipocyte differentiation using 3T3-L1 preadipocytes. In these cells, sclerostin enhanced adipocyte-specific gene expression and the accumulation of lipid deposits. Sclerostin also upregulated CCAAT/enhancer binding protein beta expression but not cell proliferation and caspase-3/7 activities. Sclerostin also attenuated canonical Wnt3a-inhibited adipocyte differentiation. Recently, the transcriptional modulator TAZ has been involved in the canonical Wnt signaling pathway. Sclerostin reduced TAZ-responsive transcriptional activity and TAZ-responsive gene expression. Transfection of 3T3 L1 cells with TAZ siRNA increased the lipid deposits and adipogenic gene expression. These results show that sclerostin upregulates adipocyte differentiation in 3T3-L1 cells, suggesting a possible role for the osteocyte derived sclerostin as a regulator of fat metabolism and as a reciprocal regulator of bone and adipose tissues metabolism. PMID- 26553152 TI - Letter from the Editor. PMID- 26553153 TI - Human Vaccines & Immunotherapeutics: News. PMID- 26553154 TI - From plant virology to vaccinology: The road less travelled. PMID- 26553155 TI - Clinical Radiology and Radiology Research in a Sea of Change. PMID- 26553156 TI - Association of pulse wave velocity with total lung capacity: A cross-sectional analysis of the BOLD London study. AB - BACKGROUND: Low lung function, measured using spirometry, has been associated with mortality from cardiovascular disease, but whether this is explained by airflow obstruction or restriction is a question that remains unanswered. OBJECTIVES: To assess the association of total lung capacity (TLC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) with several cardio metabolic and inflammatory markers. METHODS: In the follow up of the Burden of Lung Disease (BOLD) study in London, acceptable post-bronchodilator spirometric, pulse rate, pulse wave velocity and blood pressure data were obtained from 108 participants. Blood samples for measurement of cardio-metabolic and inflammatory markers were also collected from these participants. Association of lung function and volume with the different biomarkers was examined in multivariable linear regression models adjusted for potential confounders. RESULTS: Following adjustment for age, sex, height, and ethnicity, TLC (adjusted coefficient = 1.53; 95% CI: -2.57, -0.49) and FVC (adjusted coefficient = -2.66; 95% CI: -4.98, -0.34) were inversely associated with pulse wave velocity, and further adjustment for smoking status, pack-years and body mass index (BMI) did not materially change these results. FEV1 was inversely associated with systolic blood pressure, and adjustment for smoking status, pack-years and BMI made this association stronger (adjusted coefficient = -9.47; 95% CI: -15.62, -3.32). CONCLUSION: The inverse association of pulse wave velocity, which is a marker of cardiovascular disease, with TLC suggests that the association of the former with low FVC is independent of airflow obstruction. The association between FEV1 with systolic blood pressure after adjustment for FVC suggests an association with airflow obstruction rather than with restricted spirometry. PMID- 26553157 TI - Radionuclidic purity tests in (18)F radiopharmaceutIcals production process. AB - Radionuclidic purity tests of (18)F radiopharmaceuticals (Na(18)F and fluorodeoxyglucose [(18)F]FDG) and radionuclide composition analysis of irradiated water [(18)O]H2O were performed. The measurements were conducted using a High-Purity Germanium (HPGe) detector and a liquid scintillation counter. Radionuclide identification and activity measurements were performed for samples from different stages of the production process. Most of the impurities were detected on QMA (quaternary methylammonium) anion exchange columns and in liquid wastes. Using liquid scintillation counting, the activity of (3)H resulting from the (18)O[p, (3)H](16)O reaction was determined. It was shown that all of the impurities were efficiently determined and eliminated in the radiopharmaceuticals synthesis process and that the final products meet the requirements set by relevant regulations. PMID- 26553158 TI - Angiopoietin-1 and C16 Peptide Attenuate Vascular and Inflammatory Responses in Experimental Allergic Encephalomyelitis. AB - Breakdown of normal blood-brain barrier function and accompanying vascular leakage are fundamental stages in the onset of multiple sclerosis and its animal counterpart, experimental allergic encephalomyelitis. In the present study, angiopoietin-1, an endothelial growth factor well known for its role in establishing and maintaining vascular integrity, and C16, a peptide that competitively binds to integrin alphavbeta3 expressed on endothelial cells, were used to treat acute experimental allergic encephalomyelitis in Lewis rats. Angiopoietin-1 was more effective than C16 for reducing inflammation-induced vascular leakage. Moreover, treatment with a combination of angiopoietin-1 and C16 resulted in greater effects, not only in alleviating inflammation and reducing axonal loss/demyelination but also in down-regulating pro-inflammatory cytokine expression and improving electrophysiological dysfunction, than treatment with either angiopoietin-1 or C16 alone. Different protective effects were observed with angiopoietin-1 and C16 treatment suggesting that these proteins target specific receptors to act through different pathways. Furthermore, angiopoietin-1 and C16 may form the basis of a promising therapeutic strategy for experimental allergic encephalomyelitis and multiple sclerosis. PMID- 26553159 TI - The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men. AB - Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer's disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 weeks washout, and then 24 weeks of placebo (P); the second group (Group B) received the same treatments, in reverse order (Placebo, washout, and then T treatment). In group A (TeP), compared to baseline, there was a modest (1 point) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination (MMSE) following testosterone treatment. This improvement from baseline was sustained following the washout period and crossover to placebo treatment. Similar Mini Mental State Examination (MMSE) scores were observed when comparing testosterone treatment with placebo. In group B (PeT) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment. Improvements in baseline depression scores (assessed by Geriatric Depression Scale) were observed following testosterone/placebo treatment in both groups, and no difference was observed when comparing testosterone with placebo treatment. Our findings indicate a modest improvement on global cognition with testosterone treatment. Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment. PMID- 26553160 TI - Anti-Neoplastic and Calcium Modulatory Action of Caffeic Acid Phenethyl Ester and Dasatinib in C6 Glial Cells: A Therapeutic Perspective. AB - Gliomas are often recognized as highly heterogeneous cancerous phenotype. They are perpetually recurrent, obstinately resistant to treatment and hence almost incurable. Drug development studies to date have revealed only modest effect in attenuating growth of these tumors. The present study was aimed at elucidating the potential of targeting glioma through a novel combination of drugs in comparison to single agent. Here, we show that the combined administration of Caffeic acid phenethyl ester [CAPE] and Dasatinib exerts a strong antitumor action on C6 glioma cells. Combinational treatment inhibits proliferation, induces apoptosis, modulates astrocytic phenotype and decreases cell density. Results suggest that combinational therapy inhibits migration and invasiveness, decreases cell survival fraction and hence clonogenic property of C6 cells. The Nitric oxide [NO] levels were significantly reduced by combination treatment at all time points and effect was persistent over the time in comparison to single drug treatment. Atomic Absorption Spectroscopy [AAS] analysis of intracellular and extracellular calcium revealed that the treatment with CAPE and Dasatinib strongly modulates the calcium [Ca(2+)] levels. Herein, we demonstrate that treatment of C6 glioma cells with CAPE and Dasatinib significantly decrease the activity of catalase [CAT]. The results in totality suggest that the combinational therapy remarkably reduces the proliferation of glioma cells possibly through different mechanisms, targeting multiple pathways involved in tumor growth, proliferation and development implicating the relevance of using these drugs in combination therapy for effective treatment of glioma. In vitro results suggest that CAPE and Dasatinib cotreatment could be therapeutically exploited for the management of gliomas. PMID- 26553161 TI - Chemotherapy-Induced Peripheral Neuropathic Pain and Rodent Models. AB - Painful peripheral neuropathies resulting from cancer chemotherapy treatment is frequently dose-dependent and may diminish following dose reduction or termination of chemotherapy. However, dose reduction or treatment termination could lead to reemergence of the cancer. In addition, chemotherapy-induced peripheral neuropathy (CIPN) may persist long after termination of chemotherapy. Thus, there is a need for treatments to ameliorate pain during the course of an effective cancer treatment regimen. Because the mechanism underlying CIPN has yet to be fully characterized, there is a current lack of effective treatments for CIPN. Preclinical studies in CIPN rodent models have suggested a number of potential neuropathological mechanisms, which could serve as platforms for the development of novel therapeutics. Although a number of potential analgesic therapies have demonstrated robust efficacy in preclinical studies, rigorous clinical testing has yet to fully validate the preclinical findings. The lack of congruence between preclinical and clinical findings could be in part due to the phylogenetic distance between the main model species and humans. Thus, a CIPN model in nonhuman primates could serve to bridge the translational gap between laboratory findings in small animals and clinical utility. The current review points out the short comings of current CIPN rodent models and suggests the use of large animals, such as the nonhuman primate, to narrow the translational gap between preclinical and clinical findings and the discovery of novel therapeutics. PMID- 26553162 TI - Folic Acid Can Contribute to Memory Deficit and Na+, K+- ATPase Failure in the Hippocampus of Adolescent Rats Submitted to Hypoxia- Ischemia. AB - Recent findings have demonstrated a dual effect of the folic acid (FA) supplementation on the nervous system of rats. We found that FA treatment prevented memory impairment and Na(+), K(+)- ATPase inhibition in the striatum and cortex in adult rats that suffered neonatal hypoxia-ischemia (HI). However, spatial memory deficit has been associated with FA supplementation. In the present study we investigated the role of FA supplementation on spatial memory and Na(+), K(+)-ATPase activity in the hippocampus, as well as on morphologic alterations in adolescent rats submitted to neonatal HI. Wistar rats of both sexes at postnatal day (PND) 7 were submitted to Levine-Rice HI procedure. Intraperitoneal doses of FA were administered immediately before HI and repeated daily until the maximum PND 40. Hippocampal volume and striatum area were estimated and Na(+), K(+)-ATPase activity in the hippocampus was measured at PND 31. Also, the performance of the animals in the water maze was assessed and Na(+), K(+)-ATPase activity measured again at PND 52. Interestingly, HI and FA resulted in spatial memory deficits in the Morris water maze and the Na(+), K(+) ATPase activity was impaired at PND 31 in HI rats which received FA. Additionally, Na(+), K(+)-ATPase activity in adulthood showed a decrease after HI and a recovery in supplemented animals. Hippocampal and striatal atrophy were partially reversed by FA. To conclude, the present results support the hypothesis that FA supplementation during development contributes to memory deficits caused by HI and Na(+), K(+)-ATPase failure in adolescent rats, although, in adulthood, FA has been effective in reversing enzymatic activity in the hippocampus. PMID- 26553163 TI - Rabbit Models of Ocular Diseases: New Relevance for Classical Approaches. AB - Over 100 million individuals are affected by irreversible visual impairments and blindness worldwide, while ocular diseases remain a challenging problem despite significant advances in modern ophthalmology. Development of novel drugs and drug delivery mechanisms, as well as advanced ophthalmological techniques requires experimental models including animals, capable of developing ocular diseases with similar etiology and pathology, suitable for future trials of new therapeutic approaches. Although experimental ophthalmology and visual research are traditionally performed on rodent models, these animals are often unsuitable for pre-clinical drug efficacy and safety studies, as well as for testing novel drug delivery approaches, e.g. controlled release of pharmaceuticals using intra ocular implants. Therefore, rabbit models of ocular diseases are particularly useful in this context, since rabbits can be easily handled, while sharing more common anatomical and biochemical features with humans compared to rodents, including longer life span and larger eye size. This review provides a brief description of clinical, morphological and mechanistic aspects of the most common ocular diseases (dry eye syndrome, glaucoma, age-related macular degeneration, light-induced retinopathies, cataract and uveitis) and summarizes the diversity of current strategies for their experimental modeling in rabbits. Several applications of some of these models in ocular pharmacology and eye care strategies are also discussed. PMID- 26553164 TI - Coenzyme Q10 for Patients with Parkinson's Disease: A Systematic Review and Meta Analysis. AB - INTRODUCTION: Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated CoQ10 for neuroprotection against Parkinson's disease (PD). The aim of this study is to synthesize evidence from published randomized controlled trials (RCTs) about the benefit of CoQ10 supplementation for patients with Parkinson's disease. METHODS: We followed the PRISMA statement guidelines during the preparation of this systematic review and metaanalysis. A computer literature search for (PubMed, EBSCO, Web of science and Ovid Midline) was carried out. We included RCTs comparing CoQ10 with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III and Schwab and England scores were pooled as standardized mean difference (SMD) between two groups from baseline to the endpoint. RESULTS: Five RCTs (981 patients) were included in this study. The overall effect did not favor either of the two groups in terms of: total UPDRS score (SMD -0.05, 95%CI [-0.10, 0.15]), UPDRS I (SMD -0.03, 95% CI [ 0.23, 0.17]), UPDRS II (SMD -0.10, 95%CI [-0.35, 0.15]), UPDRS III (SMD -0.05, 95%CI [-0.07, 0.17]) or Schwab and England score (SMD 0.08, 95%CI [-0.13, 0.29]). CONCLUSION: CoQ10 supplementation does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease. PMID- 26553165 TI - Donepezil May Reduce Insulin-Like Growth Factor-1 (IGF-1) Levels in Alzheimer's disease. AB - OBJECTIVE: Determine if donepezil will raise the insulin-like growth factor-1 levels of patients with amnestic mild cognitive impairment and Alzheimer's disease. DESIGN: In an outpatient setting, recruit amnestic mild cognitive impairment and Alzheimer's disease patients who were to start treatment with donepezil. Measure total serum insulin-like growth factor-1 levels before and after 3-6 months of treatment. RESULTS: Twenty-four patients were recruited. After a mean duration of 129 +/- 37 days, 14 patients returned taking 5 mg (n=4) or 10 mg (n=10) donepezil per day. Twelve patients experienced decreases in their insulin-like growth factor-1 levels, one had no change, and one experienced an increase. Their mean insulin-like growth factor-1 level dropped by 13%, from 113 +/- 31 ng/ml to 98 +/- 28 ng/ml (p<0.001). CONCLUSION: Contrary to the expected increase in insulin-like growth factor-1 levels in response to donepezil that has been reported for normal elderly adults, our patients experienced decreases. This finding suggests that the somatotropic axis is altered in amnestic mild cognitive impairment and Alzheimer's disease relative to normal older adults. PMID- 26553166 TI - Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia. AB - Dystonia is a hyperkinetic disabling movement disorder. In the dt(sz) hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the KV7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective KV7.2-5 blocker indicated a pathophysiological role of an abnormal expression of KV7 channels. We therefore investigated the expression of KV7 subunits in brains of dystonic hamsters. While KV7.2 and KV7.3 subunits were unaltered, lower KV7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The KV7.2/3 subunit-preferring channel opener N-(6-chloropyridin-3-yl) 3,4- difluorobenzamide (ICA 27243; 10-30 mg/kg i.p.) failed to reduce the severity of dystonia in mutant hamsters, suggesting that the previously observed antidystonic action of retigabine is mediated by the activation of KV7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches. PMID- 26553167 TI - Rare earth activated yttrium aluminate phosphors with modulated luminescence. AB - Yttrium aluminate (Y3 A5 O12 ) was doped with different rare earth ions (i.e. Gd(3+) , Ce(3+) , Eu(3+) and/or Tb(3+) ) in order to obtain phosphors (YAG:RE) with general formula,Y3-x-a Gdx REa Al5 O12 (x = 0; 1.485; 2.97 and a = 0.03). The synthesis of the phosphor samples was done using the simultaneous addition of reagents technique. This study reveals new aspects regarding the influence of different activator ions on the morpho-structural and luminescent characteristics of garnet type phosphor. All YAG:RE phosphors are well crystallized powders containing a cubic-Y3 Al5 O12 phase as major component along with monoclinic-Y4 Al2 O9 and orthorhombic-YAlO3 phases as the impurity. The crystallites dimensions of YAG:RE phosphors vary between 38 nm and 88 nm, while the unit cell slowly increase as the ionic radius of the activator increases. Under UV excitation, YAG:Ce exhibits yellow emission due to electron transition in Ce(3+) from the 5d level to the ground state levels ((2) F5/2 , (2) F7/2 ). The emission intensity of Ce(3+) is enhanced in the presence of the Tb(3+) ions and is decreased in the presence of Eu(3+) ions due to some radiative or non-radiative processes that take place between activator ions. By varying the rare earth ions, the emission colour can be modulated from green to white and red. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553168 TI - Prescription drug coverage: implications for hormonal therapy adherence in women diagnosed with breast cancer. AB - In spite of its demonstrated benefits, many women do not initiate hormonal therapy, and among those who do, many discontinue it prematurely. We examined whether differences in hormonal therapy adherence may be at least partially explained by the availability of prescription drug coverage. Women aged 20-79 years diagnosed with stage I-III breast cancer between June 2005 and February 2007 were enrolled in the study. Women completed a mailed survey, on average 9 months after diagnosis, and again approximately 4 years later (N = 712). Adjusted logistic regression was used to predict the likelihood of initiating hormonal therapy and hormonal therapy continuation. Women who had prescription drug coverage were more likely to initiate hormonal therapy relative to women without prescription drug coverage (OR 2.91, 95 % CI 1.24-6.84). Women with prescription drug coverage were also more likely to continue hormonal therapy (OR 2.23; 95 % CI 0.99-5.05, p = 0.0543). The lowest income women were also less likely to continue hormonal therapy relative to women with annual household income that exceeded $70,000 (OR 0.55; 95 % CI 0.29-1.04) with a borderline significance of (p = 0.08). This study demonstrates the critical role of prescription drug coverage in hormonal therapy initiation and continuation, independent of health insurance coverage. These findings add to the body of literature that addresses medication adherence. Financial factors must be considered along with behavioral factors that influence adherence, which is becoming increasingly relevant to oncology as treatments are shifted to oral medications, many of which are very expensive. PMID- 26553169 TI - Effects of Organic and Waste-Derived Fertilizers on Yield, Nitrogen and Glucosinolate Contents, and Sensory Quality of Broccoli (Brassica oleracea L. var. italica). AB - Organic vegetable production attempts to pursue multiple goals concerning influence on environment, production resources, and human health. In areas with limited availability of animal manure, there is a need for considering various off-farm nutrient resources for such production. Different organic and waste derived fertilizer materials were used for broccoli production at two latitudes (58 degrees and 67 degrees ) in Norway during two years. The fertilizer materials were applied at two rates of total N (80 and 170 kg ha(-1)) and compared with mineral fertilizer (170 kg ha(-1)) and no fertilizer. Broccoli yield was strongly influenced by fertilizer materials (algae meal < unfertilized control < sheep manure < extruded shrimp shell < anaerobically digested food waste < mineral fertilizer). Yield, but not glucosinolate content, was linearly correlated with estimated potentially plant-available N. However, extruded shrimp shell and mineral NPK fertilizer gave higher glucosinolate contents than sheep manure and no fertilizer. Sensory attributes were less affected by fertilizer material and plant-available N. PMID- 26553170 TI - Divergence of the dengue virus type 2 Cosmopolitan genotype associated with two predominant serotype shifts between 1 and 2 in Surabaya, Indonesia, 2008-2014. AB - Indonesia is one of the biggest dengue endemic countries, and, thus, is an important place to investigate the evolution of dengue virus (DENV). We have continuously isolated DENV in Surabaya, the second biggest city in Indonesia, since 2008. We previously reported sequential changes in the predominant serotype from DENV type 2 (DENV-2) to DENV type 1 (DENV-1) in November 2008 and from DENV 1 to DENV-2 in July 2013. The predominance of DENV-2 continued in 2014, but not in 2015. We herein phylogenetically investigated DENV-2 transitions in Surabaya between 2008 and 2014 to analyze the divergence and evolution of DENV-2 concomitant with serotype shifts. All DENV-2 isolated in Surabaya were classified into the Cosmopolitan genotype, and further divided into 6 clusters. Clusters 1 3, dominated by Surabaya strains, were defined as the "Surabaya lineage". Clusters 4-6, dominated by strains from Singapore, Malaysia, and many parts of Indonesia, were the "South East Asian lineage". The most recent common ancestor of these strains existed in 1988, coinciding with the time that an Indonesian dengue outbreak took place. Cluster 1 appeared to be unique because no other DENV 2 isolate was included in this cluster. The predominance of DENV-2 in 2008 and 2013-14 were caused by cluster 1, whereas clusters 2 and 3 sporadically emerged in 2011 and 2012. The characteristic amino acids of cluster 1, E-170V and E-282Y, may be responsible for its prevalence in Surabaya. No amino acid difference was observed in the envelope region between strains in 2008 and 2013-14, suggesting that the re-emergence of DENV-2 in Surabaya was due to the loss or decrease of herd immunity in the 5-year period when DENV-2 subsided. The South East Asian lineage primarily emerged in Surabaya in 2014, probably imported from other parts of Indonesia or foreign countries. PMID- 26553172 TI - Food insecurity in veteran households: findings from nationally representative data. AB - OBJECTIVE: The present study is the first to use nationally representative data to compare rates of food insecurity among households with veterans of the US Armed Forces and non-veteran households. DESIGN: We used data from the 2005-2013 waves of the Current Population Survey - Food Security Supplement to identify rates of food insecurity and very low food security in veteran and non-veteran households. We estimated the odds and probability of food insecurity in veteran and non-veteran households in uncontrolled and controlled models. We replicated these results after separating veteran households by their most recent period of service. We weighted models to create nationally representative estimates. SETTING: Nationally representative data from the 2005-2013 waves of the Current Population Survey - Food Security Supplement. SUBJECTS: US households (n 388 680). RESULTS: Uncontrolled models found much lower rates of food insecurity (8.4 %) and very low food security (3.3 %) among veteran households than in non veteran households (14.4 % and 5.4 %, respectively), with particularly low rates among households with older veterans. After adjustment, average rates of food insecurity and very low food security were not significantly different for veteran households. However, the probability of food insecurity was significantly higher among some recent veterans and significantly lower for those who served during the Vietnam War. CONCLUSIONS: Although adjusting eliminated many differences between veteran and non-veteran households, veterans who served from 1975 and onwards may be at higher risk for food insecurity and should be the recipients of targeted outreach to improve nutritional outcomes. PMID- 26553173 TI - Accuracy and reaction time in recognition of facial emotions in people with multiple sclerosis. AB - INTRODUCTION: Facial emotional expression constitutes a basic guide in the social interaction and, thus, the alterations in its expression or recognition imply an important limitation for the communication. On the other hand, cognitive impairment and the presence of depressive symptoms, which are commonly found in patients with multiple sclerosis, it is unknown how they influence cognitive function and depression on emotional recognition. AIMS: To consider the evaluation of time reaction and response accuracy of facial expression recognition in people affected by multiple sclerosis, and to assess the possible variables that may be modulating the emotion recognition, such as depression and cognitive functions. SUBJECTS AND METHODS: The study has a cross-sectional non experimental design with a single measurement. The sample is compound by 85 participants, 45 diagnosed as multiple sclerosis and 40 control subjects. RESULTS: Multiple sclerosis subjects reveal significant differences in both reaction time and response accuracy in neuropsychological tests in comparison to the control group. Explanatory models were identified in the emotional recognition. CONCLUSION: Multiple sclerosis subjects face difficulties at recognising facial emotions; and differences at attention memory, processing speed and depressive symptomatology were observed in regard to the control group. PMID- 26553174 TI - [Relationship between ultrasound measurements of the median nerve and electrophysiological severity in carpal tunnel syndrome]. AB - INTRODUCTION: Ultrasonography is a tool that has advanced a great deal in the diagnosis of neural compressive pathologies, such as carpal tunnel syndrome (CTS). In order to plan the treatment it is important to establish the severity of the pathology, which means that it would be important to know the capacity of ultrasonography to determine the extent to which the median nerve is compromised at this level. AIM: To investigate the correlation between ultrasound measurements and electrophysiological severity in patients with CTS. PATIENTS AND METHODS: Ultrasound measurements were performed with 59 subjects (97 wrists) who were referred to have an electroneurogram (ENG) due to suspected CTS. According to the ENG, the subjects were classified as healthy, mild, moderate or severe CTS. The relationship between the ultrasound measurements and the results of the ENG were later analysed in terms of their severity. The ROC (receiver operating characteristic) curves were calculated for the optimal cut-off values in each group, taking into account their severity. RESULTS: Both ultrasound measurements showed a correlation with the severity of the CTS determined by ENG. The cross sectional area of the median nerve in the wrist (CSA-W) showed the highest correlation (r = 0.613). CONCLUSIONS: There is a relation between the ultrasound measurements of the median nerve, especially in the CSA-W, and the severity of CTS in the clinical context. These measurements could be used as complementary data to diagnose CTS and to determine its severity. PMID- 26553175 TI - [A pilot study on the living with a chronic process scale in patients with Parkinson's disease]. AB - INTRODUCTION: To be able to provide patients with a chronic illness personalised care, it is necessary to know how they live with their disorder. Today, there is no validated scale that assesses this aspect. AIM: To present the pilot study of the preliminary version of the living with a chronic process scale (EC-PC, from the name in Spanish) carried out in patients with Parkinson's disease (PD) in Spain. PATIENTS AND METHODS: A preliminary version of the scale was produced from a literature review and the participation of experts in chronic processes and in PD. Fifteen patients, in all the different stages of PD, answered the preliminary version of the EC-PC (39 items) and a questionnaire about the EC-PC. The viability/acceptability and preliminary aspects of internal consistency were analysed. RESULTS: No domain showed any floor or ceiling effects, but 43.6% of the items had a ceiling effect. The corrected item-total correlation was satisfactory, except in five items. The internal consistency of the five domains was satisfactory, with alpha indexes of 0.81-0.92 and item homogeneity coefficients of 0.19-0.43. The patients identified three items as ambiguous and difficult to answer. Based on these results, 12 items were eliminated and the final version of the EC-PC was drafted, its content being considered satisfactory following its evaluation by expert professionals. CONCLUSIONS: The EC-PC, pending validation, is a viable scale of potential interest in the clinical and community healthcare setting for assessing the ability to live with a chronic process like PD. PMID- 26553176 TI - [IgG4- and MPO-ANCA-associated hypertrophic pachymeningitis]. AB - INTRODUCTION: Idiopathic hypertrophic pachymeningitis is a fibroinflammatory immune-mediated disease of the dura mater. Its diagnosis requires the preclusion of infectious, tumoral and other inflammatory diseases. In recent years new entities have been reported that can present with hypertrophic pachymeningitis, such as IgG4-associated disease and MPO-ANCA+ pachymeningitis, as a form of vasculitis limited to the central nervous system. CASE REPORT: We describe the case of a 64 years-old male with headaches and cervicalgia, predominantly at night, and clinical signs and symptoms of spinal cord compression. Following the diagnosis of craniocervical hypertrophic pachymeningitis provided by the magnetic resonance imaging study, an aetiological study was conducted. Infectious and tumoral diseases were precluded. The clinical features did not show any systemic involvement and high levels of IgG4 and MPO-ANCA+ were found in the results of the analyses. The clinical signs and symptoms quickly improved following treatment with corticoids. CONCLUSIONS: IgG4-related disease and MPO-ANCA associated vasculitis limited to the central nervous system can account for a high percentage of the cases of hypertrophic pachymeningitis that were considered idiopathic, and their diagnosis requires a biopsy and a histological study. PMID- 26553177 TI - [The social brain: neurobiological bases of clinical interest]. AB - INTRODUCTION: Human social capacities are developmentally late and unique. They allow for a specialisation that enhances the availability of resources and facilitates reproduction. Our social complexity rests on specific circuits and mechanisms, which are analysed here. DEVELOPMENT: The following are put into operation for those purposes: knowledge of the other by means of empathy, specific mechanisms that endow us with the capacity to detect defrauders, genetic and biochemical factors, and the autonomic nervous system. Empathy is the basic mechanism in sociability. It has different levels of complexity (emotional, cognitive, attribution), with specific anatomical differentiation. Social matters are linked to emotional ones, and this in turn to the homeostatic aspects. Hence, physical and social pain share an anatomical matrix and therapies. We are social beings of a selfish biological nature, which we adjust thanks to a special capacity to detect defrauders, which is dominant over those involving planning or abstraction. Oxytocin is the essential prosocial neurochemical mediator. Serotonin and the enzyme MAO are considered as having an antisocial capacity, which is dependent on the interaction with adverse environments. Finally, the vagal system, which is more recent phylogenetically speaking and myelinated, that of the dorsal nucleus of the vagus nerve, is a requirement for warm and leisurely social interaction. CONCLUSIONS: The neurobiology of social matters makes it possible to recognise disorders affecting this behaviour in structural injuries (vascular, of the white matter, dementias, etc.), neurodevelopmental disorders (autism), psychiatric illnesses (schizophrenia) or personality disorders. There are a number of promising therapeutic interventions (transcranial magnetic stimulation, drugs). The addition of cultural and environmental factors to the neurobiological ones introduces a greater amount of ecological complexity, but without lessening the validity of what it outlined. PMID- 26553178 TI - [Guillain-Barre syndrome. Early ultrasound findings]. PMID- 26553179 TI - [40.a Reunion de la Sociedad de Neurofisiologia Clinica de las Comunidades de Valencia y Murcia. Communications]. PMID- 26553180 TI - [Deep vein thrombosis and dural fistula: a case with infrequent clinical characteristics]. PMID- 26553182 TI - The Creation of a Model Pediatric Ward for African American Children in 1920s Kansas City. PMID- 26553181 TI - Children's Food and Beverage Promotion on Television to Parents. AB - BACKGROUND: Nutritionally poor foods are heavily advertised to children on television. Whether those same products are also advertised to parents on television has not been systematically examined. METHODS: This study is a content analysis of advertisements for children's packaged foods and beverages aired over US network, cable, and syndicated television for 1 year (2012 to 2013). The target audience of each advertisement was defined as children or parents based on advertisement content, where parent-directed advertisements included emotional appeals related to family bonding and love. Advertisement characteristics and patterns of airtime were compared across target audience, and the proportion of total airtime devoted to advertisements targeting parents was computed. RESULTS: Fifty-one children's food or beverage products were advertised over the study year, 25 (49%) of which were advertised directly to parents. Parent-directed advertisements more often featured nutrition and health messaging and an active lifestyle than child-directed advertisements, whereas child-directed advertisements more frequently highlighted fun and product taste. Over all products, 42.4% of total airtime was devoted to advertisements that targeted parents. The products with the most amount of airtime over the study year were ready-to-eat cereals, sugar-sweetened beverages, and children's yogurt, and the proportion of total advertisement airtime for those products devoted to parents was 24.4%, 72.8%, and 25.8%, respectively. DISCUSSION: Television advertisements for children's packaged foods and beverages frequently targeted parents with emotional appeals and messaging related to nutrition and health. Findings are of concern if exposure to such advertisements among parents may shape their beliefs about the appropriateness of nutritionally questionable children's foods and beverages. PMID- 26553183 TI - Identification of Barriers to Pediatric Care in Limited-Resource Settings: A Simulation Study. AB - OBJECTIVES: Eighty percent of the 10 million annual deaths in children aged <5 years in developing countries are estimated to be avoidable, with improvements in education for pediatric emergency management being a key factor. Education must take into account cultural considerations to be effective. Study objectives were: (1) to use simulation to identify factors posing barriers to patient care in limited resource settings (LRS); and (2) to understand how simulations in LRS can affect communication and decision-making processes. METHODS: A qualitative study was conducted at 17 different sites in 12 developing countries in Asia, Latin America, and Africa. Data from observations of 68 in situ simulated pediatric emergencies were coded for thematic analysis. Sixty-two different "key informants" were interviewed regarding perceived benefit of simulations. RESULTS: Coding of observations and interviews yielded common themes: impact of culture on team hierarchy, impact of communication and language barriers on situational awareness, systematic emergency procedures, role delineation, shared cognition and resource awareness through simulation, logistic barriers to patient care, and use of recognition-primed decision-making by experienced clinicians. Changes in clinical environments were implemented as a result of simulations. CONCLUSIONS: Ad hoc teams in LRS face challenges in caring safely for patients; these include language and cultural barriers, as well as environmental and resource constraints. Engaging teams in simulations may promote improved communication, identification of systems issues and latent threats to target for remediation. There may be a role for training novices in use of recognition-primed or algorithmic decision-making strategies to improve rapidity and efficiency of decisions in LRS. PMID- 26553184 TI - Pituicytoma and Cushing's Disease in a 7-Year-Old Girl: A Mere Coincidence? AB - Pituicytoma is a tumor extremely rare in childhood, with only 4 cases reported in literature. It is thought to arise from the specialized glial elements called "pituicytes." The association of pituicytoma and Cushing's disease (CD) has been described only once so far, in an adult patient. A 7-year-old girl was referred for clinical signs of hypercortisolism, and a diagnosis of CD was made. MRI revealed 2 pathologic areas in the pituitary gland. The patient underwent surgery, with microscopic transsphenoidal approach, and a well-circumscribed area of pathologic tissue was identified and removed. Surprisingly, histologic and immunohistochemical study provided unequivocal evidence of pituicytoma. No pituitary adenoma could be identified. For persistent hypercortisolism, the patient necessitated transsphenoidal endoscopic reintervention and 2 other lesions were removed. By immunohistological examination, these lesions were confirmed to be corticotropin-secreting adenoma. Unfortunately, there was no postoperative decrease in corticotropin and cortisol levels, and the patient underwent bilateral laparoscopic adrenalectomy. Considering that we report a second case of association of pituicytoma and corticotropin-secreting adenoma, that CD is infrequent, and pituicytoma is extremely rare in childhood, the coexistence of these 2 tumors should not be considered a mere coincidence. To date, there is no conclusive evidence about the origin of these different subtypes of pituitary tumors. This case supports the hypothesis that these tumors share a common progenitor cell, which could be the folliculostellate cell. PMID- 26553185 TI - Predicting Nonhemolytic Neonatal Hyperbilirubinemia. AB - BACKGROUND: Before hospital discharge, newborn infants should be assessed for the risk of excessive hyperbilirubinemia. We determined maternal and obstetric risk factors for hyperbilirubinemia in infants born at term (gestational age >=37 weeks) to form an individualized risk assessment tool for clinical use. METHODS: This was a population-based study with data from the Swedish Medical Birth Register from 1999 to 2012, including 1,261,948 singleton infants. Outcome was defined as infants diagnosed with hyperbilirubinemia (N = 23,711), excluding all cases of hemolytic (immune-mediated or other specified hemolytic) diseases of the newborn. RESULTS: Risk factors with an adjusted odds ratio (aOR) for neonatal hyperbilirubinemia of >=1.5 (medium-sized effect or more) were gestational age 37 to 38 weeks (aOR = 2.83), failed vacuum extraction (aOR = 2.79), vacuum extraction (aOR = 2.22), Asian mother (aOR = 2.09), primipara (aOR = 2.06), large for-gestational-age infant (aOR = 1.84), obese mother (aOR = 1.83), and small-for gestational-age infant (aOR = 1.66). Planned cesarean delivery (CD) was associated with a reduced risk (aOR = 0.45). Without any of these risk factors (normal birth weight infant delivered vaginally at 39 to 41 weeks' gestation by a non-Asian, nonobese, multiparous mother) the rate of nonhemolytic neonatal hyperbilirubinemia was 0.7%. In relation to the combined load of different risk factors, rates of neonatal hyperbilirubinemia ranged from 0.2% to 25%. CONCLUSIONS: Collection of a few easily available maternal and obstetric risk factors predicts >100-fold variation in the incidence of neonatal hyperbilirubinemia. The information provided herein enables individualized risk prediction with interactions between different risk factors taken into account. PMID- 26553186 TI - Neonatal Sulfhemoglobinemia and Hemolytic Anemia Associated With Intestinal Morganella morganii. AB - Sulfhemoglobinemia is a rare disorder characterized by the presence of sulfhemoglobin in the blood. It is typically drug-induced and may cause hypoxia, end-organ damage, and death through oxygen deprivation. We present here a case of non-drug-induced sulfhemoglobinemia in a 7-day-old preterm infant complicated by hemolytic anemia. Microbiota compositional analysis of fecal samples to investigate the origin of hydrogen sulphide revealed the presence of Morganella morganii at a relative abundance of 38% of the total fecal microbiota at the time of diagnosis. M morganii was not detected in the fecal samples of 40 age-matched control preterm infants. M morganii is an opportunistic pathogen that can cause serious infection, particularly in immunocompromised hosts such as neonates. Strains of M morganii are capable of producing hydrogen sulphide, and virulence factors include the production of a diffusible alpha-hemolysin. The infant in this case survived intact through empirical oral and intravenous antibiotic therapy, probiotic administration, and red blood cell transfusions. This coincided with a reduction in the relative abundance of M morganii to 3%. Neonatologists should have a high index of suspicion for intestinal pathogens in cases of non-drug-induced sulfhemoglobinemia and consider empirical treatment of the intestinal microbiota in this potentially lethal condition. PMID- 26553187 TI - Biological and Social Influences on Outcomes of Extreme-Preterm/Low-Birth Weight Adolescents. AB - BACKGROUND AND OBJECTIVES: The importance of biological versus social influences on long-term outcomes of extremely preterm children is debatable. The goal of this study was to determine the relative contributions of biological and social exposures to outcomes into adolescence in extremely preterm survivors, hypothesizing that biological exposures would be more important early, but social exposures would dominate later. METHODS: The study included 298 consecutive survivors born at <28 weeks' gestation or weighing <1000 g in Victoria, Australia (during 1991-1992), and 262 normal birth weight (>2499 g) control subjects who were used to standardize outcomes for the preterm group. Cognitive ability was assessed at 2, 5, 8, and 18 years of age. Academic achievement was assessed at 8 and 18 years of age. RESULTS: The differences between the preterm and control groups for cognitive and academic scores remained relatively constant over time. The biological variables most associated with worse outcomes within the extremely preterm group were intraventricular hemorrhage and postnatal corticosteroid therapy. Of the social variables, being reared in a multilingual household was disadvantageous early, with social class and maternal education becoming more important for later outcomes. The strength of the biological associations mostly equaled or exceeded those of social exposures, even in late adolescence. CONCLUSIONS: Contrary to expectations, several perinatal biological exposures had large and persistent adverse associations with cognitive and academic outcomes among extremely preterm survivors. As expected, some social variables assumed increasing importance in later years but mostly did not diminish or exceed the important biological associations. PMID- 26553188 TI - Systemwide Solutions to Improve Early Intervention for Developmental-Behavioral Concerns. PMID- 26553189 TI - Risks in a Trial of an Innovative Treatment of Duchenne Muscular Dystrophy. AB - Studies of innovative therapies for muscular dystrophy raise unique ethical issues. The disease is currently untreatable and relentlessly progressive. A number of potentially efficacious treatments are being developed, but like all treatments, they may have unforeseen adverse effects. Nevertheless, patients and families, facing a bleak future, may be willing to take the gamble and try the treatments. Many doctors are eager to study them. But should institutional review boards approve them? This article discusses these issues and recounts the ways that one such study elicited different responses from different institutional review boards. PMID- 26553190 TI - 3% Hypertonic Saline Versus Normal Saline in Inpatient Bronchiolitis: A Randomized Controlled Trial. AB - BACKGROUND AND OBJECTIVES: Bronchiolitis, the most common reason for hospitalization in children younger than 1 year in the United States, has no proven therapies effective beyond supportive care. We aimed to investigate the effect of nebulized 3% hypertonic saline (HS) compared with nebulized normal saline (NS) on length of stay (LOS) in infants hospitalized with bronchiolitis. METHODS: We conducted a prospective, randomized, double-blind, controlled trial in an urban tertiary care children's hospital in 227 infants younger than 12 months old admitted with a diagnosis of bronchiolitis (190 completed the study); 113 infants were randomized to HS (93 completed the study), and 114 to NS (97 completed the study). Subjects received 4 mL nebulized 3% HS or 4 mL 0.9% NS every 4 hours from enrollment until hospital discharge. The primary outcome was median LOS. Secondary outcomes were total adverse events, subdivided as clinical worsening and readmissions. RESULTS: Patient characteristics were similar in groups. In intention-to-treat analysis, median LOS (interquartile range) of HS and NS groups was 2.1 (1.2-4.6) vs 2.1 days (1.2-3.8), respectively, P = .73. We confirmed findings with per-protocol analysis, HS and NS groups with 2.0 (1.3 3.3) and 2.0 days (1.2-3.0), respectively, P = .96. Seven-day readmission rate for HS and NS groups were 4.3% and 3.1%, respectively, P = .77. Clinical worsening events were similar between groups (9% vs 8%, P = .97). CONCLUSIONS: Among infants admitted to the hospital with bronchiolitis, treatment with nebulized 3% HS compared with NS had no difference in LOS or 7-day readmission rates. PMID- 26553193 TI - Endocrine Pathology Society Hubert Wolfe Award for 2015: Call for Nominations. PMID- 26553191 TI - Evaluating the impact of cannabis use on thalamic connectivity in youth at clinical high risk of psychosis. AB - BACKGROUND: Disruptions in thalamic functional connectivity have been observed in people with schizophrenia and in youth at clinical high risk (CHR) of psychosis. However, the impact of environmental risk factors for psychosis on thalamic dysconnectivity is poorly understood. We tested whether thalamic dysconnectivity is related to patterns of cannabis use in a CHR sample. METHODS: 162 CHR and 105 control participants were assessed on cannabis use severity, frequency, and age at onset of first use as part of the North American Prodrome Longitudinal Study and completed resting-state fMRI scans. Whole-brain thalamic functional connectivity maps were generated using individual subjects' anatomically defined thalamic seeds. RESULTS: Thalamic connectivity did not significantly correlate with current cannabis use severity or frequency in either CHR or controls. In CHR cannabis users, a significant correlation emerged between attenuated thalamic connectivity with left sensory/motor cortex and a younger age at onset of cannabis use. CHR who used cannabis before age 15 did not differ on thalamic connectivity as compared to CHR who used after age 15 or CHR who were cannabis naive. No group differences in thalamic connectivity emerged when comparing CHR separated by moderate/high use frequency, low-frequency or cannabis naive. CONCLUSIONS: Although a younger age at onset of cannabis use may be associated with disrupted thalamo-cortical coupling, cannabis use does not appear to be an identifying characteristic for thalamic connectivity in CHR with moderate/high use frequency compared to low-frequency users or CHR who are cannabis naive. PMID- 26553192 TI - Med14 cooperates with brg1 in the differentiation of skeletogenic neural crest. AB - BACKGROUND: An intricate gene regulatory network drives neural crest migration and differentiation. How epigenetic regulators contribute to this process is just starting to be understood. RESULTS: We found that mutation of med14 or brg1 in zebrafish embryos resulted in a cluster of neural crest cell-related defects. In med14 or brg1 mutants, neural crest cells that form the jaw skeleton were specified normally and migrated to target sites. However, defects in their subsequent terminal differentiation were evident. Transplantation experiments demonstrated that med14 and brg1 are required directly in neural crest cells. Analysis of med14; brg1 double mutant embryos suggested the existence of a strong genetic interaction between members of the Mediator and BAF complexes. CONCLUSIONS: These results suggest a critical role for Mediator and BAF complex function in neural crest development, and may also clarify the nature of defects in some craniofacial abnormalities. PMID- 26553194 TI - Adverse cutaneous drug eruptions: current understanding. AB - Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID- 26553195 TI - Effect of a topical nonsteroidal anti-inflammatory agent (0.1 % pranoprofen) on acute central serous chorioretinopathy. AB - PURPOSE: To investigate the effects of topical pranoprofen 0.1 % on acute central serous chorioretinopathy (CSC). METHODS: The medical records of 52 cases (52 patients) of CSC were retrospectively reviewed. Twenty-six patients were treated with topical pranoprofen 0.1 % (treatment group) and 26 patients did not receive treatment (control group). Baseline and follow-up values for visual acuity, subfoveal choroidal thickness (SCT), subretinal fluid (SRF) maximum height, and central macular thickness (CMT) were examined and compared between groups. RESULTS: In the treatment group, mean SCT decreased from 365.5 +/- 52.9 MUm at baseline to 288.9 +/- 36.1 MUm at 6 months after initiation of treatment (p = 0.005). Both SRF maximum height and CMT were also decreased from baseline at 1 month (SRF maximum height, baseline: 221.5 +/- 108.4, 1 month: 97.7 +/- 54.3 MUm, p = 0.002; CMT, baseline: 403.9 +/- 114.6, 1 month: 270.1 +/- 37.9 MUm, p = 0.003). In the control group, SCT decreased throughout the follow-up period, but the change was not significant. Subretinal fluid maximum height and CMT were significantly decreased after 3 months in the control group (SRF, baseline: 265.4 +/- 112.4 MUm, 6 months: 64.8 +/- 116.9 MUm, p = 0.005; CMT, baseline: 459.1 +/- 104.9 MUm, 6 months: 304.6 +/- 92.8 MUm, p < 0.001). Visual acuity was improved from baseline in both groups after 6 months, but the improvement was only significant in the treatment group (p = 0.002). The rate of disease recurrence was lower in the treatment group (23 %) than in the control group (38 %), but this difference between groups was not statistically significant (p = 0.229, chi square test). CONCLUSIONS: Topical pranoprofen 0.1 % was effective in treating acute CSC, as demonstrated by an increase in visual acuity and a decrease in SRF, SCT, and CMT after treatment. These results suggest that topical pranoprofen 0.1 % may be useful in treating patients with acute CSC. PMID- 26553196 TI - Modified corneal incisions in intraoperative floppy iris syndrome (IFIS)-prone patients. AB - BACKGROUND: We aimed to report a simple technique that involves modified anterior (to the limbus) elongated corneal incisions in order to reduce the incidence and severity of intraoperative floppy iris syndrome (IFIS) and related complications. METHODS: This was a retrospective study of phacoemulsification cataract surgeries performed by a single surgeon on patients receiving tamsulosin or alfuzosin between 1 January 2009 and 31 July 2012 at Meir Medical Center, Kfar-Sava, Israel. We recorded preoperative gender, age, alpha-antagonist medication, coexisting pseudoexfoliation (PXF), and intraoperative use of ophthalmic viscosurgical devices (OVDs), pupil size, complications, IFIS grading and the need for additional operative strategies to manage IFIS. Elongated corneal incisions were performed approximately 1 mm anterior to the limbus. RESULTS: Ninety-three eyes of 81 men were included. Mean age was 76.5 years (range 55 to 96 years). Forty-seven eyes (40 patients) had documented use of alfuzosin and 45 eyes (40 patients) of tamsulosin. One patient received both. The overall rate of IFIS was 22.6 % (n = 21). Eyes of patients who were treated with alfuzosin had a milder grading (p < 0.001) and an overall lower percentage of IFIS compared to tamsulosin (4.26 % versus 42.22 % respectively, p < 0.001). No additional strategies were used to manage IFIS during surgery. No intraoperative complications occurred. CONCLUSION: Anterior elongated incisions are simple and efficient in preventing IFIS, exempting the surgeon from the use of additional expensive devices or materials in most cases. They do not limit the surgeon to one strategy, and therefore, if necessary, another may be applied at any given time. PMID- 26553197 TI - Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high-risk penetrating keratoplasty: a 2-year follow-up study. AB - PURPOSE: In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after high-risk penetrating keratoplasty. METHODS: One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group. RESULTS: During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p < 0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR = 11, 95.0 % CI 4.8 25, p < 0.0001). Among 98 MMF-treated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction. CONCLUSIONS: MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case. PMID- 26553198 TI - Steady-state multifocal visual evoked potential (ssmfVEP) using dartboard stimulation as a possible tool for objective visual field assessment. AB - PURPOSE: To investigate whether a conventional, monitor-based multifocal visual evoked potential (mfVEP) system can be used to record steady-state mfVEP (ssmfVEP) in healthy subjects and to study the effects of temporal frequency, electrode configuration and alpha waves. METHODS: Multifocal pattern reversal VEP measurements were performed at 58 dartboard fields using VEP recording equipment. The responses were measured using m-sequences with four pattern reversals per m step. Temporal frequencies were varied between 6 and 15 Hz. Recordings were obtained from nine normal subjects with a cross-shaped, four-electrode device (two additional channels were derived). Spectral analyses were performed on the responses at all locations. The signal to noise ratio (SNR) was computed for each response using the signal amplitude at the reversal frequency and the noise at the neighbouring frequencies. RESULTS: Most responses in the ssmfVEP were significantly above noise. The SNR was largest for an 8.6-Hz reversal frequency. The individual alpha electroencephalogram (EEG) did not strongly influence the results. The percentage of the records in which each of the 6 channels had the largest SNR was between 10.0 and 25.2 %. CONCLUSION: Our results in normal subjects indicate that reliable mfVEP responses can be achieved by steady-state stimulation using a conventional dartboard stimulator and multi-channel electrode device. The ssmfVEP may be useful for objective visual field assessment as spectrum analysis can be used for automated evaluation of responses. The optimal reversal frequency is 8.6 Hz. Alpha waves have only a minor influence on the analysis. Future studies must include comparisons with conventional mfVEP and psychophysical visual field tests. PMID- 26553199 TI - Severe cranial neuropathies caused by falls from heights in children. AB - PURPOSE: Falls from heights are the most common traumatic event associated with emergency department visits in children. This study investigated the incidence and clinical course of cranial neuropathies caused by falls from heights in children. METHODS: The computerized records of a tertiary pediatric medical center were searched for all patients admitted to the emergency department in 2004-2014 with a head injury caused by falling from a height. Those with cranial neuropathies involving optic and eye-motility disturbances were identified, and their clinical, imaging, and outcome data were evaluated. RESULTS: Of the estimated 61,968 patients who presented to the emergency department during the study period because of a fall, 18,758 (30.3 %) had head trauma. Only 12 (seven boys, five girls, average age 6.7 years) had a visual disturbance. Eight were diagnosed with traumatic optic neuropathy, one after a 6-month delay, including two with accompanying cranial nerve (CN) III injuries. Five patients had anisocoria or an abnormal pupillary response to light at presentation, one patient had CN VI paralysis and temporary vision loss, and one patient had an isolated CN III injury diagnosed on follow-up. Visual improvement varied among the patients. CONCLUSION: Cranial neuropathies due to falls from heights are rare in children and are associated with high visual morbidity. Vision or ocular motility impairment, especially monocular vision loss, may be missed during acute intake to the emergency department, and a high index of suspicion is needed. Assessment of the pupillary response to light is essential. PMID- 26553201 TI - Evaluation of diagnostic accuracy in CT perfusion analysis in moyamoya disease. AB - PURPOSE: The purpose of the present study was to determine optimal threshold of vascular pixel elimination (VPE) for CT perfusion (CTP) and to assess diagnostic accuracy of CTP by comparing with xenon enhanced CT (XeCT) in moyamoya disease. MATERIALS AND METHODS: Twenty-three patients underwent XeCT and CTP. Cerebral blood flow (CBF) images were generated for XeCT and CTP using nine types of software. Region of interest (ROI) measurement was performed on XeCT-CBF and CTP CBF. Linear regression analysis was performed between XeCT-CBF and CTP-CBF in all software, without and with VPE. The Pearson correlation coefficient was calculated, and an optimal threshold was determined based on maximum correlation coefficients. Correlation coefficients at various VPE thresholds including data of no-VPE were compared with each other. The maximum correlation coefficient at the optimal threshold was also compared. RESULTS: Optimal thresholds varied among software types (0.8-2.2 and 7-14 ml/100 g in relative and absolute VPE, respectively). There were significant differences between correlation coefficients at a range of VPE thresholds compared to no-VPE in most software types. There were significant differences in maximum correlation coefficient at optimal threshold among various software types. CONCLUSION: Optimal threshold of VPE for CTP could be determined and diagnostic accuracy of CTP varied among software types in moyamoya disease. PMID- 26553202 TI - CRISPR sabotage. AB - The biological arms race generally involves the rapid co-evolution of anti-virus systems in host organisms and of anti-anti-virus systems in their viral parasites. The CRISPR-Cas system is an example of a prokaryotic immune system in which such co-evolution occurs, as was recently demonstrated by the characterization of a set of viral anti-CRISPR proteins. PMID- 26553200 TI - Assessment of dorsal instability of the ulnar head in the distal radioulnar joint: comparison between normal wrist joints and cases of ruptured extensor tendons. AB - In the present study, the adaptability of the distal radioulnar joint (DRUJ) was evaluated using conventional computed tomography (CT) evaluation methods. In addition, we investigated/compared a new method to evaluate dorsal displacement of the ulnar head. Our subjects consisted of 32 healthy volunteers (64 wrists) and 11 patients (13 wrists) with extensor tendon injuries related to dorsal displacement of the ulnar head. To diagnose instability in the DRUJ based on CT scans, the radioulnar line method and the modified radioulnar line method were measured. Instability was evaluated by the new method that the ulnar head was located on the dorsal side from a line involving the peak of Lister's tubercle in parallel to this baseline was regarded as showing abnormal dorsal displacement of the ulnar head. The diagnostic accuracy of each method was calculated. The sensitivities, specificities, false-positive rates, positive predictive values and the negative predictive value of new methods were better than other two methods. The new method that we recommend is simple. Based on the results of this study, an evaluation of normal/abnormal dorsal displacement of the ulnar head in the DRUJ using the new method may be useful for determining the timing of surgery. PMID- 26553203 TI - An observation of a severely disabled infant chimpanzee in the wild and her interactions with her mother. AB - We report the physical and behavioral development of one severely disabled female infant chimpanzee (Pan troglodytes schweinfurthii) of the well-habituated M group in the Mahale Mountains National Park. We documented interactions between the infant and its mother and with other group members. Congenital disabilities occur in many primate species, including chimpanzees. However, there have been only a few case studies of congenitally disabled chimpanzee infants and no reports examining how a chimpanzee mother copes with such a disabled infant in the wild. The observed infant exhibited symptoms resembling Down syndrome, similar to those reported previously for a captive chimpanzee. The mother did not allow nonrelatives to take care of the infant even though she had been previously relatively tolerant of allomothering by nonrelatives. The mother's compensatory care for her infant's disabilities and allomothering of the infant by its sister might have helped it to survive for 23 months in the wild. Other group members did not show any aversive or fearful reactions to the disabled infant. PMID- 26553204 TI - Integrating sampling techniques and inverse virtual screening: toward the discovery of artificial peptide-based receptors for ligands. AB - A novel heuristic using an iterative select-and-purge strategy is proposed. It combines statistical techniques for sampling and classification by rigid molecular docking through an inverse virtual screening scheme. This approach aims to the de novo discovery of short peptides that may act as docking receptors for small target molecules when there are no data available about known association complexes between them. The algorithm performs an unbiased stochastic exploration of the sample space, acting as a binary classifier when analyzing the entire peptides population. It uses a novel and effective criterion for weighting the likelihood of a given peptide to form an association complex with a particular ligand molecule based on amino acid sequences. The exploratory analysis relies on chemical information of peptides composition, sequence patterns, and association free energies (docking scores) in order to converge to those peptides forming the association complexes with higher affinities. Statistical estimations support these results providing an association probability by improving predictions accuracy even in cases where only a fraction of all possible combinations are sampled. False positives/false negatives ratio was also improved with this method. A simple rigid-body docking approach together with the proper information about amino acid sequences was used. The methodology was applied in a retrospective docking study to all 8000 possible tripeptide combinations using the 20 natural amino acids, screened against a training set of 77 different ligands with diverse functional groups. Afterward, all tripeptides were screened against a test set of 82 ligands, also containing different functional groups. Results show that our integrated methodology is capable of finding a representative group of the top-scoring tripeptides. The associated probability of identifying the best receptor or a group of the top-ranked receptors is more than double and about 10 times higher, respectively, when compared to classical random sampling methods. PMID- 26553205 TI - Ultrasound-Based Carotid Elastography for Detection of Vulnerable Atherosclerotic Plaques Validated by Magnetic Resonance Imaging. AB - Ultrasound-based carotid elastography has been developed to estimate the mechanical properties of atherosclerotic plaques. The objective of this study was to evaluate the in vivo capability of carotid elastography in vulnerable plaque detection using high-resolution magnetic resonance imaging as reference. Ultrasound radiofrequency data of 46 carotid plaques from 29 patients (74 +/- 5 y old) were acquired and inter-frame axial strain was estimated with an optical flow method. The maximum value of absolute strain rate for each plaque was derived as an indicator for plaque classification. Magnetic resonance imaging of carotid arteries was performed on the same patients to classify the plaques into stable and vulnerable groups for carotid elastography validation. The maximum value of absolute strain rate was found to be significantly higher in vulnerable plaques (2.15 +/- 0.79 s(-1), n = 27) than in stable plaques (1.21 +/- 0.37 s( 1), n = 19) (p < 0.0001). Receiver operating characteristic curve analysis was performed, and the area under the curve was 0.848. Therefore, the in vivo capability of carotid elastography to detect vulnerable plaques, validated by magnetic resonance imaging, was proven, revealing the potential of carotid elastography as an important tool in atherosclerosis assessment and stroke prevention. PMID- 26553206 TI - Virtual Touch Tissue Imaging Quantification Shear Wave Elastography: Prospective Assessment of Cervical Lymph Nodes. AB - The goal of this study was to prospectively evaluate the diagnostic performance of Virtual Touch tissue imaging quantification (VTIQ) shear wave elastography in the discrimination of benign and malignant cervical lymph nodes in routine clinical practice. Shear wave velocity was analyzed using VTIQ in 100 patients with 100 histologically proven cervical lymph nodes. Diagnostic performance was evaluated using receiver operating characteristic curve analysis and leave-one out cross-validation. Agreement between measurements was assessed with intra class correlation coefficients. The mean shear wave velocity was significantly higher in metastatic lymphadenopathy (4.46 +/- 1.46 m/s) than in benign lymphadenopathy (2.71 +/- 0.85 m/s) (p < 0.001) at a cutoff level of 3.34 m/s. The cross-validated accuracy, sensitivity and specificity were 77%, 78.9% and 74.4%, respectively. Agreement of measurements with VTIQ was excellent (intra class correlation coefficient = 0.961). VTIQ shear wave elastography may be a feasible quantitative imaging method for differentiating benign and malignant cervical lymph nodes. PMID- 26553207 TI - Interval Colorectal Cancer After Colonoscopy: Exploring Explanations and Solutions. AB - There is good evidence that colorectal cancer (CRC) screening has been successful at reducing both CRC incidence and death. Colonoscopy, utilized as either a primary screening tool or a follow-up exam when other screening tests are positive, has significantly contributed to these encouraging trends. However, it is well recognized that colonoscopy is not perfectly sensitive for the detection of neoplasia and that CRC can be diagnosed within a short interval following a colonoscopy that did not detect one. The literature surrounding these cases has rapidly expanded over the last decade. Specifically, studies aimed at understanding the frequency of these events and the likely explanations for their occurrence have been performed. This review will highlight current knowledge around the epidemiology of interval post colonoscopy CRC (PCCRC). The common explanations for these cancers including missed lesions, new lesions, and incompletely resected lesions will be reviewed and their contribution to interval PCCRC estimated. Finally, the relationship of these putative explanations to potential opportunities to prevent interval PCCRC will be explored. Current approaches to prevention largely center on consistent adherence to quality colonoscopy standards. Future approaches include advances in technology to better visualize the colon and adequately resect detected neoplasia. Finally, improvement in training as well as development of a culture of continuous quality improvement will be essential to maximize the benefits of colonoscopy in daily clinical practice. PMID- 26553208 TI - Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases. AB - OBJECTIVES: Predicting severe acute pancreatitis (AP) remains a challenge. The present study compares admission blood urea nitrogen (BUN), hematocrit, and creatinine, as well as changes in their levels over 24 h, aiming to determine the most accurate laboratory test for predicting persistent organ failure and pancreatic necrosis. METHODS: Clinical data of 1,612 AP patients, enrolled prospectively in three independent cohorts (University of Pittsburgh, Brigham and Women's Hospital, Dutch Pancreatitis Study Group), were abstracted. The predictive accuracy of the studied laboratories was measured using area under the receiver-operating characteristic curve (AUC) analysis. A pooled analysis was conducted to determine their impact on the risk for persistent organ failure and pancreatic necrosis. Finally, a classification tree was developed on the basis of the most accurate laboratory parameters. RESULTS: Admission hematocrit >=44% and rise in BUN at 24 h were the most accurate in predicting persistent organ failure (AUC: 0.67 and 0.71, respectively) and pancreatic necrosis (0.66 and 0.67, respectively), outperforming the other laboratory parameters and the acute physiology and chronic health evaluation-II score. In a pooled analysis, admission hematocrit >=44% and rise in BUN at 24 h were associated with an odds ratio of 3.54 and 5.84 for persistent organ failure, and 3.11 and 4.07, respectively, for pancreatic necrosis. In addition, the classification tree illustrated that when both admission hematocrit was >=44% and BUN levels increased at 24 h, the rates of persistent organ failure and pancreatic necrosis reached 53.6% and 60.3%, respectively. CONCLUSIONS: Admission hematocrit >=44% and rise in BUN at 24 h may be the optimal predictive tools in clinical practice among existing laboratory parameters and scoring systems. PMID- 26553209 TI - Molecular genetics of naringenin biosynthesis, a typical plant secondary metabolite produced by Streptomyces clavuligerus. AB - BACKGROUND: Some types of flavonoid intermediates seemed to be restricted to plants. Naringenin is a typical plant metabolite, that has never been reported to be produced in prokariotes. Naringenin is formed by the action of a chalcone synthase using as starter 4-coumaroyl-CoA, which in dicotyledonous plants derives from phenylalanine by the action of a phenylalanine ammonia lyase. RESULTS: A compound produced by Streptomyces clavuligerus has been identified by LC-MS and NMR as naringenin and coelutes in HPLC with a naringenin standard. Genome mining of S. clavuligerus revealed the presence of a gene for a chalcone synthase (ncs), side by side to a gene encoding a P450 cytochrome (ncyP) and separated from a gene encoding a Pal/Tal ammonia lyase (tal). Deletion of any of these genes results in naringenin non producer mutants. Complementation with the deleted gene restores naringenin production in the transformants. Furthermore, naringenin production increases in cultures supplemented with phenylalanine or tyrosine. CONCLUSION: This is the first time that naringenin is reported to be produced naturally in a prokariote. Interestingly three non-clustered genes are involved in naringenin production, which is unusual for secondary metabolites. A tentative pathway for naringenin biosynthesis has been proposed. PMID- 26553210 TI - Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration. AB - INTRODUCTION: Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. METHODS: The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. RESULTS: We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. CONCLUSIONS: We have successfully differentiated rESCs to glia enriched RPCs and retinal neuron enriched RPCs in vitro. The retinal neuron enriched rESC-RPC2 protected the structure and function of retina in rats with genetic retinal degeneration and could be a candidate cell source for treating some degenerative retinal diseases in human trials. PMID- 26553211 TI - mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion. AB - BACKGROUND: We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. METHODS AND RESULTS: mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real time activity data and 16 personal factors with a 10 000 steps/day goal. Forty eight outpatients (46% women, 21% nonwhite) enrolled with a mean+/-SD age of 58+/ 8 years, body mass index of 31+/-6 kg/m(2), and baseline activity of 9670+/-4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], -580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). CONCLUSIONS: An automated tracking texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. CLINICAL TRIAL REGISTRATION: URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812. PMID- 26553212 TI - Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non-End-Stage Renal Disease. AB - BACKGROUND: Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (LVH). However, little clinical data are currently available regarding the detailed correlation between LVH and renal function in elderly patients with non-end-stage renal disease. METHODS AND RESULTS: A total of 300 in- and outpatients (more than 60 years of age, non-end-stage renal disease), 251 with LVH and 49 without LVH, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study. One observation period of 12 months was used to detect rapid kidney function decline. The evaluations of cardiac structure and function were performed via echocardiography. The multivariable logistic analysis showed patients with LVH had a much higher risk of rapid kidney function decline than those without LVH. Additionally, the baseline left ventricular mass index was 140 (125-160) g/m(2) in the non-chronic kidney disease group, 152 (130-175) g/m(2) in the mild chronic kidney disease group (estimated glomerular filtration rate (eGFR)>=60 ml/min/1.73 m(2)), and 153 (133-183) g/m(2) in the severe chronic kidney disease group (eGFR<60 ml/min/1.73 m(2)), with a significant difference (P=0.009). CONCLUSIONS: Our data demonstrate that a high rate of renal function decline contributes to pathological LVH in non-end-stage renal disease elderly patients and that LVH is positively associated with renal function decline followed by an increased risk of rapid kidney function decline. PMID- 26553213 TI - Impact of Alcohol Consumption on Substrate Remodeling and Ablation Outcome of Paroxysmal Atrial Fibrillation. AB - BACKGROUND: The effect of alcohol consumption on substrate remodeling and ablation outcome of paroxysmal atrial fibrillation (PAF) remains unknown. METHODS AND RESULTS: We performed circumferential pulmonary vein isolation (CPVI) and voltage mapping of left atrium (LA) during sinus rhythm in 122 consecutive patients with symptomatic PAF (age, 55.4+/-9.4 years; 73.8% men). Low-voltage zones (LVZs) were semiquantitatively estimated and presented as low-voltage index (LVI). Each patient's daily alcohol consumption history was recorded at baseline and classified into alcohol abstainers, moderate drinkers, and heavy drinkers based on the National Institute on Alcohol Abuse and Alcoholism definition. Follow-up was >=12 months for AF recurrence. Alcohol abstainers and moderate and heavy drinkers were 70 (57.4%), 13 (10.6%), and 39 (32.0%), respectively. In total, LVZs were observed in 44 patients (36.1%). Daily alcohol consumption independently predicted presence of LVZs (odds ratio [OR], 1.097; 95% confidence interval [CI], 1.001-1.203; P=0.047). During mean follow-up of 20.9+/-5.9 months, 40 patients (35.1%) experienced AF recurrence. Success rate was 81.3%, 69.2%, and 35.1% in alcohol abstainers, moderate drinkers, and heavy drinkers, respectively (overall log rank, P<0.001). Multivariate analysis showed that both alcohol consumption and LVI were independent predictors of AF recurrence (hazard ratio [HR], 1.579; 95% CI, 1.085-2.298; P=0.017; HR, 2.188; 95% CI, 1.582-3.026; P<0.001, respectively). Furthermore, mediation analysis revealed that LVZs acted as a partial mediator in effect of alcohol consumption on AF ablation outcomes. CONCLUSIONS: Daily alcohol consumption was associated with atrial remodelling, and heavy drinkers have substantial risk for AF recurrence after CPVI. PMID- 26553214 TI - Cancer and Its Association With the Development of Coronary Artery Calcification: An Assessment From the Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Although cancer and its corresponding therapies are associated with increased ischemic heart disease, the temporal relationship between cancer and the development of coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is unknown. METHODS AND RESULTS: Among 3122 men and women free of cardiovascular disease and cancer in the Multi-Ethnic Study of Atherosclerosis trial, CAC scoring was performed at baseline (2000-2002) and at follow-up (2010 2012). Over this 10-year period, 85 men (age 63.6+/-8.3 years) and 50 women (age 62.1+/-9.8 years) were diagnosed with cancer (predominantly breast, lung, or uterine [52%] in women and prostate or colorectal [78%] in men). The other 2987 subjects (age 59.6+/-9.2 years for men, 59.7+/-9.4 years for women) remained cancer free. The incidence of new CAC (baseline Agatston score of zero converting to detectable CAC) was modeled with relative risk regression and compared for cancer versus no cancer. Increase in pre-existing CAC was compared in these groups using linear regression of log transformed CAC. The incidence of CAC was independently associated with cancer history (relative risk 1.32 [P=0.04] and 1.29 [P=0.01] for women and men, respectively). In participants with CAC at baseline, a clear difference of CAC progression was not observed between cancer and noncancer participants (P=0.6 for women, P=0.2 for men). CONCLUSIONS: A diagnosis of cancer is associated with the development of CAC even after accounting for atherosclerotic risk factors. However, in individuals with pre existing CAC, it is not clear whether the presence of cancer accelerates CAC over time. PMID- 26553215 TI - Coronary Artery Vessel Healing Pattern, Short and Long Term, After Implantation of the Everolimus-Eluting Bioresorbable Vascular Scaffold. AB - BACKGROUND: Although the Absorb bioresorbable vascular scaffold is increasingly used in daily clinical practice for the treatment of coronary artery disease, the exact vascular healing pattern and the resorption process in humans is unknown because histological data are derived only from animal studies. METHODS AND RESULTS: We have obtained 4 autopsies (5 scaffolds) since August 2013. Duration of bioresorbable vascular scaffold implantation ranged from 3 to 501 days. All autopsies and histological assessments were performed by dedicated cardiovascular pathologists. At 1 week after bioresorbable vascular scaffold implantation, struts were covered with a fine layer of fibrin and platelets. At 113 days, the scaffold struts were fully covered with smooth muscle cells. Hyaline eosinophilic and proteoglycan material infiltrating the scaffold struts was observed at 501 days after implantation. At all time points, we observed the presence of multinuclear foreign body giant cells adjacent to the scaffold struts. CONCLUSIONS: Resorption and healing processes after bioresorbable vascular scaffold implantation in human patients mirror those observed in porcine models. The presence of multinucleated foreign body giant cells at both short- and long term follow-up needs further investigation and may be related to a low-grade absorptive inflammatory response to the polymer. PMID- 26553216 TI - Long-Term Risk of Stroke in Patients With Type 1 and Type 2 Diabetes Following Coronary Artery Bypass Grafting. AB - BACKGROUND: We performed a nationwide population-based cohort study to investigate the long-term risk of stroke after coronary artery bypass grafting in patients with type 1 and type 2 diabetes. METHODS AND RESULTS: All patients who underwent primary coronary artery bypass grafting in Sweden from 2000 through 2011 were included from the SWEDEHEART register. We excluded patients with prior stroke, and patients who had a stroke or died within 30 days of surgery. The National Diabetes Register was used to identify patients with type 1 and type 2 diabetes. Incident stroke (ischemic and hemorrhagic), and all-cause mortality was obtained by record linkage with the National Patient Register and the Cause of Death register. We used multivariable Cox regression to estimate the risk of stroke in relation to type of diabetes. A total of 53 820 patients (type 1 diabetes [n=714], type 2 diabetes [n=10 054], no diabetes [n=43 052]) were included. During a mean follow-up of 7.4 years (398 337 person-years), in total, 8.0% (n=4296) of the patients had a stroke: 7.3% (n=52) in patients with type 1 diabetes, 9.1% (n=915) in patients with type 2 diabetes, and 7.7% (n=3329) in patients with no diabetes. The multivariable adjusted hazard ratio (95% CI) for all stroke was 1.59 (1.20-2.11) in type 1 diabetes, and 1.32 (1.23-1.43) in type 2 diabetes. CONCLUSIONS: The long-term risk for stroke after coronary artery bypass grafting was increased in patients with type 1 and type 2 diabetes, compared to patients with no diabetes. PMID- 26553217 TI - Systematic review of the diagnostic category muscle dysmorphia. AB - OBJECTIVES: (1) To collect, analyze and synthetize the evidence on muscle dysmorphia diagnosis as defined by Pope et al. and (2) To discuss its appropriate nosology and inclusion as a specific category in psychiatric classificatory systems. METHOD: A systematic search in the MEDLINE, the PsycNET, the LILACS and SciELO databases and in the International Journal of Eating Disorders was conducted looking for articles published between January 1997 and October 2014 and in EMBASE database between January 1997 and August 2013. Only epidemiological and analytical studies were considered for selection. The methodological quality of included studies was assessed according to the Evidence-Based Mental Health and the National Health and Medical Research Council's guidelines. The support for inclusion of muscle dysmorphia in psychiatric classificatory systems was examined against Blashfield et al.'s criteria. RESULTS: Thirty-four articles were considered eligible out of 5136. Most of the studies were cross-sectional and enrolled small, non-clinical samples. The methodological quality of all selected papers was graded at the lowest hierarchical level due to studies' designs. Forty one percent of the publications considered the available evidence insufficient to support the inclusion of muscle dysmorphia in any existing category of psychiatric disorders. The current literature does not fulfill Blashfield et al.'s criteria for the inclusion of muscle dysmorphia as a specific entity in psychiatric diagnostic manuals. CONCLUSION: The current evidence does not ensure the validity, clinical utility, nosological classification and inclusion of muscle dysmorphia as a new disorder in classificatory systems of mental disorders. PMID- 26553218 TI - Borderline personality disorder and polycystic ovary syndrome. PMID- 26553219 TI - Climate change and psychiatry. PMID- 26553220 TI - Muscling in on body image disorders: What is the nosological status of muscle dysmorphia? PMID- 26553221 TI - Cultural 'Inclusion' or Institutional Decolonisation: How should prisons address the mental health needs of Indigenous prisoners? PMID- 26553223 TI - Creative Cognition and Brain Network Dynamics. AB - Creative thinking is central to the arts, sciences, and everyday life. How does the brain produce creative thought? A series of recently published papers has begun to provide insight into this question, reporting a strikingly similar pattern of brain activity and connectivity across a range of creative tasks and domains, from divergent thinking to poetry composition to musical improvisation. This research suggests that creative thought involves dynamic interactions of large-scale brain systems, with the most compelling finding being that the default and executive control networks, which can show an antagonistic relation, tend to cooperate during creative cognition and artistic performance. These findings have implications for understanding how brain networks interact to support complex cognitive processes, particularly those involving goal-directed, self-generated thought. PMID- 26553224 TI - Expression of activated signal transducer and activator of transcription-3 as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma. AB - BACKGROUND: Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor constitutively active and aberrantly expressed in various types of malignancies, and the expression of p-STAT3 has been recognized as a predictor of poor survival. It remains unclear how variations in p-STAT3 expression influence clinical outcomes in esophageal squamous cell carcinoma (ESCC). METHODS: Between 1 January 2008 and 1 November 2013, 153 advanced esophageal squamous cell carcinoma patients (stage IV) from two cancer centers in West China were treated with paclitaxel and cisplatin. We retrospectively analyzed the clinical outcomes of patients with ESCC and examined the correlation between p-STAT3 levels and clinical outcomes in esophageal cancer patients. RESULTS: Among the 153 patients, positive p-STAT3 expression was observed in 73 of 153 (47.7 %) cases. The median PFS for patients with positive expression of p STAT3 and negative expression of p-STAT3 was 5.0 months and 6.9 months, respectively (P < 0.001). The median overall survival was significantly higher in patients with p-STAT3 negative tumors than in those with p-STAT3 positive tumors (9.9 vs 8.9 months, P = 0.026). Kaplan-Meier survival analysis showed that p STAT3 expression was statistically indicative of a poor prognosis for progression free survival. CONCLUSIONS: These data showed that p-STAT3 expression was significantly associated with poor prognosis in patients with esophageal cancer and could be used as a predictive and prognostic marker in esophageal cancer. PMID- 26553222 TI - Adaptive Pulvinar Circuitry Supports Visual Cognition. AB - The pulvinar is the largest thalamic nucleus in primates and one of the most mysterious. Endeavors to understand its role in vision have focused on its abundant connections with the visual cortex. While its connectivity mapping in the cortex displays a broad topographic organization, its projections are also marked by considerable convergence and divergence. As a result, the pulvinar is often regarded as a central forebrain hub. Moreover, new evidence suggests that its comparatively modest input from structures such as the retina and superior colliculus may critically shape the functional organization of the visual cortex, particularly during early development. Here we review recent studies that cast fresh light on how the many convergent pathways through the pulvinar contribute to visual cognition. PMID- 26553225 TI - Clinical impact of potentially inappropriate medications during hospitalization of acutely ill older patients with multimorbidity. AB - OBJECTIVE: To identify potentially inappropriate medications (PIMs), to compare drug changes between geriatric and other medical wards, and to investigate the clinical impact of PIMs in acutely hospitalized older adults. SETTING AND SUBJECTS: Retrospective study of 232 home-dwelling, multimorbid older adults (aged >=75 years) acutely admitted to Vestfold Hospital Trust, Norway. MAIN OUTCOME MEASURES: PIMs were identified by Norwegian general practice (NORGEP) criteria and Beers' 2012 criteria. Clinical correlates were laboratory measures, functional and mental status, physical frailty, and length of stay. RESULTS: Mean (SD) age was 86 (5.7) years, and length of stay was 6.5 (4.8) days. During the stay, the mean number of drugs used regularly changed from 7.8 (3.6) to 7.9 (3.6) (p = 0.22), and drugs used pro re nata (prn) changed from 1.4 (1.6) to 2.0 (1.7) (p < 0.001). The prevalence of any PIM changed from 39.2% to 37.9% (p = 0.076), while anticholinergics and benzodiazepines were reduced significantly (p <= 0.02). The geriatric ward reduced drug dosages (p < 0.001) and discontinued PIMs (p < 0.001) significantly more often than other medical wards. No relations between number of PIMS and clinical outcomes were identified, but the concomitant use of >=3 psychotropic/opioid drugs was associated with reduced hand-grip strength (p <= 0.012). CONCLUSION: Hospitalization did not change polypharmacy or PIMs. Drug treatment was more appropriate on the geriatric than other medical wards. No clinical impact of PIMs was observed, but prescribers should be vigilant about concomitant prescription of >=3 psychotropics/opioids. KEY POINTS: Acute hospitalization of older patients with multimorbidity did not increase polypharmacy or potentially inappropriate medications. Prescription of anticholinergics and benzodiazepines was significantly reduced. The geriatric ward reduced drug dosages and discontinued potentially inappropriate medications more frequently than the other medical wards. PMID- 26553226 TI - Network analysis of an in vitro model of androgen-resistance in prostate cancer. AB - BACKGROUND: The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer). METHODS: We established an androgen independent subline from LNCaP cells by prolonged exposure to androgen deprivation. We examined phenotypic profiles and performed RNA-sequencing. The reads generated were compared to human clinical samples and were analysed using differential expression, pathway analysis and protein-protein interaction networks. RESULTS: After 24 weeks of androgen-deprivation, LNCaP cells had increased proliferative and invasive behaviour compared to parental LNCaP, and its growth was no longer responsive to androgen. We identified key genes and pathways that overlap between our cell line and clinical RNA sequencing datasets and analysed the overlapping protein-protein interaction network that shared the same pattern of behaviour in both datasets. Mechanisms bypassing androgen receptor signalling pathways are significantly enriched. Several steroid hormone receptors are differentially expressed in both datasets. In particular, the progesterone receptor is significantly differentially expressed and is part of the interaction network disrupted in both datasets. Other signalling pathways commonly altered in prostate cancer, MAPK and PI3K-Akt pathways, are significantly enriched in both datasets. CONCLUSIONS: The overlap between the human and cell-line differential expression profiles and protein networks was statistically significant showing that the cell-line model reproduces molecular patterns observed in clinical castrate resistant prostate cancer samples, making this cell line a useful tool in understanding castrate resistant prostate cancer. Pathway analysis revealed similar patterns of enriched pathways from differentially expressed genes of both human clinical and cell line datasets. Our analysis revealed several potential mechanisms and network interactions, including cooperative behaviours of other nuclear receptors, in particular the subfamily of steroid hormone receptors such as PGR and alteration to gene expression in both the MAPK and PI3K-Akt signalling pathways. PMID- 26553228 TI - Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia. AB - BACKGROUND: This study was conducted to describe the clinical and genetic features of patients with late infantile metachromatic leukodystrophy. METHODS: Clinical and genetic manifestations of five Taiwanese patients with late infantile metachromatic leukodystrophy from January 2003 to April 2014 were reviewed. The genetic features of such patients reported in Asian countries during a period of 20 years were also analyzed. RESULTS: The median age at disease onset was 1 year and 3 months with the first clinical symptom being gait disturbance. All five patients became bed-ridden at a median age of 2 years and 5 months. Nerve conduction velocity revealed demyelinating polyneuropathy and brain MRI disclosed tigroid and leopard skin pattern of dysmyelination in all 5 patients. All patients had decreased ARSA activities in leukocytes accounting for 15.88% to 30.75% of controls. Five novel mutations, p.A316D, p.G303R, p.Q176X, p.R293X, and c.749 insGCGGGCCA, were identified in our case series. Eighteen patients, including our 5 patients, were reported in Asian countries. A total of 22 different disease-causing alleles were found, in which p.W320X was identified in Taiwan and China, and p.G101V was found in Taiwan and Korea. CONCLUSIONS: Patients with late infantile metachromatic leukodystrophy exhibited a rapid and devastating clinical course. The pattern of dysmyelination on brain MRI together with peripheral demyelination polyneuropathy indicates that evaluation of ARSA activity in leukocytes is warranted. A wide diversity of ARSA gene mutations was noted in Asia. PMID- 26553227 TI - Early astrocytosis in autosomal dominant Alzheimer's disease measured in vivo by multi-tracer positron emission tomography. AB - Studying autosomal dominant Alzheimer's disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer's disease (AD) because reactive astrocytes surround beta-amyloid (Abeta) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar Abeta, astrocytosis and cerebral glucose metabolism with the radiotracers (11)C-Pittsburgh compound-B (PIB), (11)C-deuterium-L-deprenyl (DED) and (18)F-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7). Multivariate analysis using the combined data from all radiotracers clearly separated the different groups along the first and second principal components according to increased PIB retention/decreased FDG uptake (component 1) and increased DED binding (component 2). Presymptomatic ADAD mutation carriers showed significantly higher PIB retention than non-carriers in all brain regions except the hippocampus. DED binding was highest in presymptomatic ADAD mutation carriers. This suggests that non-fibrillar Abeta or early stage plaque depostion might interact with inflammatory responses indicating astrocytosis as an early contributory driving force in AD pathology. The novelty of this finding will be investigated in longitudinal follow-up studies. PMID- 26553229 TI - Repeated Blood Pressure Measurements in Childhood in Prediction of Hypertension in Adulthood. AB - Hypertension may be predicted from childhood risk factors. Repeated observations of abnormal blood pressure in childhood may enhance prediction of hypertension and subclinical atherosclerosis in adulthood compared with a single observation. Participants (1927, 54% women) from the Cardiovascular Risk in Young Finns Study had systolic and diastolic blood pressure measurements performed when aged 3 to 24 years. Childhood/youth abnormal blood pressure was defined as above 90th or 95th percentile. After a 21- to 31-year follow-up, at the age of 30 to 45 years, hypertension (>140/90 mm Hg or antihypertensive medication) prevalence was found to be 19%. Carotid intima-media thickness was examined, and high-risk intima media was defined as intima-media thickness >90th percentile or carotid plaques. Prediction of adulthood hypertension and high-risk intima-media was compared between one observation of abnormal blood pressure in childhood/youth and multiple observations by improved Pearson correlation coefficients and area under the receiver operating curve. When compared with a single measurement, 2 childhood/youth observations improved the correlation for adult systolic (r=0.44 versus 0.35, P<0.001) and diastolic (r=0.35 versus 0.17, P<0.001) blood pressure. In addition, 2 abnormal childhood/youth blood pressure observations increased the prediction of hypertension in adulthood (0.63 for 2 versus 0.60 for 1 observation, P=0.003). When compared with 2 measurements, third observation did not provide any significant improvement for correlation or prediction (P always >0.05). A higher number of childhood/youth observations of abnormal blood pressure did not enhance prediction of adult high-risk intima-media thickness. Compared with a single measurement, the prediction of adult hypertension was enhanced by 2 observations of abnormal blood pressure in childhood/youth. PMID- 26553230 TI - Nox and Inflammation in the Vascular Adventitia. PMID- 26553231 TI - Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure. AB - Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches. Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney. PMID- 26553232 TI - SPRINT, or False Start, Toward a Lower Universal Treated Blood Pressure Target in Hypertension. PMID- 26553233 TI - J Curve and Cuff Artefact, and Diagnostic Inertia in Resistant Hypertension. PMID- 26553235 TI - SPRINT: What Remains Unanswered and Where Do We Go From Here? PMID- 26553234 TI - SPRINT Trial Results: Latest News in Hypertension Management. PMID- 26553237 TI - High level of GHR nuclear translocation in skeletal muscle of a hyperplasic transgenic zebrafish. AB - It has been reported that nuclear translocation of growth hormone receptor (GHR) may directly activate cell proliferation in mammals and birds. However, this phenomenon has not yet been described in fish. Recently, we have developed a transgenic zebrafish that overexpresses GHR in a muscle-specific manner. Considering that this transgenic model exhibits hyperplasic muscle growth, the present work aims at verifying the relationship between GHR nuclear translocation and muscle cell proliferation. This relationship was evaluated by the phosphorylation state of the proliferative MEK/ERK pathway, expression of nuclear import-related genes, immunostaining of phospho-histone H3 (PH3) as a proliferation marker, and nuclear GHR localization. The results showed a significant decrease in the phosphorylation state of ERK1/2 proteins in transgenics. Moreover, there was an increase in expression of three out of four importin genes analyzed parallel to a large flow of GHR displacement toward and into the nucleus of transgenic muscle cells. Also, transgenics presented a marked increase in PH3 staining, which indicates cell proliferation. These findings, as far as we know, are the first report suggesting a proliferative action of GHR in fish as a consequence of its increased nuclear translocation. Thus, it appears that the nuclear migration of cytokine receptors is a common event among different taxonomic groups. In addition, the results presented here highlight the possibility that these membrane proteins may be involved more directly than previously thought in the control of genes related to cell growth and proliferation. PMID- 26553239 TI - Responsibility deal for alcohol has failed, says report. PMID- 26553238 TI - Acceptability of Novel Small-Quantity Lipid-Based Nutrient Supplements for Complementary Feeding in a Peri-Urban South African Community. AB - BACKGROUND: Small-quantity lipid-based nutritional supplements (SQ-LNS) may potentially be used for home fortification in poor settings, where low nutrient dense complementary foods are commonly used for infant feeding. However, they need to be acceptable to succeed. OBJECTIVE: This study assessed the acceptability of 2 novel, SQ-LNS (A and B) for supplementing complementary foods among infants aged 6 to 12 months in a peri-urban South African community. METHODS: Both supplements were soy-based pastes and contained micronutrients and essential fatty acids. In addition, supplement B contained docosahexaenoic acid, arachidonic acid, phytase and l-lysine. Mother-infant pairs were enrolled in a 2 part trial. Part 1 (n = 16) was a test-feeding trial with a crossover randomized design, and a 5-point hedonic scale was used for sensory evaluation (disagree = 1, agree = 5). Part 2 (n = 38) was a 2-week, home-use trial followed by focus group discussions. RESULTS: In part 1, more than 70% of mothers reported a score >=4 on sensory attributes for both SQ-LNSs indicating that both supplements were well perceived. In part 2, the mean reported consumption over the 2-week period was 65.3% +/- 34.2% and 62.0% +/- 31.3% of the 20 g daily portion for supplements A and B, respectively. Focus group discussions confirmed a positive attitude toward the supplements in the study population. CONCLUSION: This study showed acceptance of both SQ-LNSs in terms of sensory characteristics as well as in terms of practicality for home use. PMID- 26553236 TI - Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial. AB - Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ~124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ~120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306. PMID- 26553240 TI - Long-range tactile masking occurs in the postural body schema. AB - Long-range tactile masking has been reported between mirror symmetric body locations. This suggests a general principle of contralateral inhibition between corresponding points on each side of the body that may serve to enhance distinguishing touches on the two halves of the body. Do such effects occur before or after posture is added to the body schema? Here, we address this question by exploring the effect of arm position on long-range tactile masking. The influence of arm position was investigated using different positions of both the test and masking arms. Tactile sensitivity was measured on one forearm, while vibrotactile-masking stimulation was applied to the opposite arm or to a control site on the shoulder. No difference was found in sensitivity when test arm position was varied. Physical contact between the arms significantly increased the effectiveness of a masking stimulus applied to the other arm. Long-range masking between the arms was strongest when the arms were held parallel to each other and was abolished if the position of either the test arm or the masking arm was moved from this position. Modulation of the effectiveness of masking by the position of both the test and masking arms suggests that these effects occur after posture information is added to the body's representation in the brain. PMID- 26553242 TI - Competency-based education is beneficial for professional development. PMID- 26553241 TI - The Munich-Evaluation-of-Mentoring-Questionnaire (MEMeQ)--a novel instrument for evaluating proteges' satisfaction with mentoring relationships in medical education. AB - BACKGROUND: Despite the widespread recognition of the importance of mentoring in medical education, valid and reliable instruments for evaluating the relationship of mentors and proteges are lacking. The aim of this study was to develop a feasible instrument to measure the satisfaction with mentoring relationships. METHODS: Based on two existing questionnaires, the authors developed an instrument to evaluate the weighted satisfaction of mentoring relationships, emphasizing the proteges' individual expectations and needs. Proteges first define individual areas of interest in their mentoring relationship, then assign relative levels of personal importance to them and finally rate their individual level of satisfaction with their mentors' support in each area of interest. In order to evaluate psychometric properties as well as acceptance and feasibility the investigators conducted a multi-method-study. RESULTS: 134 proteges were included in the study. The instrument was neither perceived as distressing nor time-consuming. The two scores of the questionnaire correlated closely with the overall satisfaction regarding mentoring relationships (OSM, Rho: 0.66, p <.001 and Rho: 0.53, p < .001). CONCLUSIONS: The authors propose MEMeQ as a reliable, valid and flexible instrument for measuring the weighted satisfaction of proteges with their individual mentoring relationship in medical education. Further research is needed to evaluate the generalizability of MEMeQ across other institutions and mentoring programs to add to its validity. PMID- 26553243 TI - Competence-based education misses the essence of the medical profession. PMID- 26553244 TI - A reappraisal of Cerebavis cenomanica (Aves, Ornithurae), from Melovatka, Russia. AB - The evolution of the avian brain is of crucial importance to studies of the transition from non-avian dinosaurs to modern birds, but very few avian fossils provide information on brain morphological development during the Mesozoic. An isolated specimen from the Cenomanian of Melovatka in Russia was described by Kurochkin and others as a fossilized brain, designated the holotype of Cerebavis cenomanica Kurochkin and Saveliev and tentatively referred to Enantiornithes. We have previously highlighted that this specimen is an incomplete skull, rendering the diagnostic characters invalid and Cerebavis cenomanica a nomen dubium. We provide here a revised diagnosis of Cerebavis cenomanica based on osteological characters, and a reconstruction of the endocranial morphology (= brain shape) based on MUCT investigation of the braincase. Absence of temporal fenestrae indicates an ornithurine affinity for Cerebavis. The brain of this taxon was clearly closer to that of modern birds than to Archaeopteryx and does not represent a divergent evolutionary pathway as originally concluded by Kurochkin and others. No telencephalic wulst is present, suggesting that this advanced avian neurological feature was not recognizably developed 93 million years ago. PMID- 26553245 TI - Transport properties of track-etched membranes having variable effective pore lengths. AB - The transport rate of molecules through polymeric membranes is normally limited because of their micrometer-scale thickness which restricts their suitability for more practical application. To study the effect of effective pore length on the transport behavior, polymer membranes containing cylindrical and asymmetric shaped nanopores were prepared through a two-step ion track-etching technique. Permeation experiments were performed separately to investigate the transport properties (molecular flux and selectivity) of these track-etched membranes. The permeation data shows that the molecular flux across membranes containing asymmetric nanopores is higher compared to those having cylindrical pores. On the other hand, the cylindrical pore membranes exhibit higher selectivity than asymmetric pores for the permeation of charged molecules across the membrane. Current-voltage (I-V) measurements of single-pore membranes further verify that asymmetric pores exhibit lower resistance for the flow of ions and therefore show higher currents than cylindrical pores. Moreover, unmodified and polyethyleneimine (PEI) modified asymmetric-shaped pore membranes were successfully used for the separation of cationic and anionic analyte molecules from their mixture, respectively. In this study, two distinct effects (pore geometry and pore density, i.e. number of pores cm(-2)), which mainly influence membrane selectivity and molecular transport rates, were thoroughly investigated in order to optimize the membrane performance. In this context, we believe that membranes with high molecular transport rates could readily find their application in molecular separation and controlled drug delivery processes. PMID- 26553246 TI - Evolution of solidification texture during additive manufacturing. AB - Striking differences in the solidification textures of a nickel based alloy owing to changes in laser scanning pattern during additive manufacturing are examined based on theory and experimental data. Understanding and controlling texture are important because it affects mechanical and chemical properties. Solidification texture depends on the local heat flow directions and competitive grain growth in one of the six <100> preferred growth directions in face centered cubic alloys. Therefore, the heat flow directions are examined for various laser beam scanning patterns based on numerical modeling of heat transfer and fluid flow in three dimensions. Here we show that numerical modeling can not only provide a deeper understanding of the solidification growth patterns during the additive manufacturing, it also serves as a basis for customizing solidification textures which are important for properties and performance of components. PMID- 26553247 TI - Hospital care and drug costs from five years before until two years after the diagnosis of Alzheimer's disease in a Finnish nationwide cohort. AB - AIMS: The aim of our study was to investigate costs related to hospital care and drugs utilizing register-based data from five years before until two years after the diagnosis of Alzheimer's disease (AD) in a nationwide cohort. METHODS: Finnish nationwide MEDALZ cohort includes all incident cases with clinically verified diagnosis of AD diagnosed during 2005-2011. The study population included 70,718 persons with AD and age-, gender- and region-of-residence-matched control persons. Data of medical care costs was derived from the prescription register and hospital discharge register. Costs of hospital care were calculated according to Finnish healthcare system unit costs. Costs in six month periods before and after the diagnosis per person-years were analyzed. RESULTS: Persons with AD had higher mean total medical care costs per person-years starting from 0.5-1 years before the diagnosis of AD and remained at a higher level until two years after the diagnosis. The difference in mean total medical care costs was at its highest at six months after the diagnosis (cost difference ?5088). After that, persons with AD had costs that reached approximately double those without AD. Hospital care costs constituted the major share (78-84%) of the total medical care costs in both persons with and without AD, whereas drug costs had a minor role. Increase in drug costs was caused by anti-dementia drugs. CONCLUSIONS: Costs of hospital stays constituted the most significant portion of medical care costs for persons with AD. Further research should be focused on the causes of hospitalization periods. PMID- 26553248 TI - Ethnic differences in asthma treatment among Swedish adolescents: A multilevel analysis of individual heterogeneity. AB - AIMS: Adolescents with immigrant or ethnic minority background suffering from asthma receive on average less appropriate anti-asthmatic medication (AAM) than the majority population. However, those findings are based on analyses of differences between group averages which prevents our understanding of individual heterogeneity around the averages. Taking into account individual socioeconomic factors and medical needs, we performed multilevel analysis in order to evaluate if maternal country of birth (MCOB) accurately identifies adolescents with inappropriate AAM use. METHODS: Using the Swedish Medical Birth Register, we identified all singleton children born between 1988 and 1991 who were residing in the country until they turned 17 and had complete information on the study variables. We applied a two-level multilevel logistic regression analysis with 62 MCOBs at the second and 755,894 children at the first level. Adjusting for socioeconomic and medical factors using a risk score, and including the socioeconomic characteristics of the MCOBs, we obtained both measures of association (odds ratio (OR)) and measures of variance (Intra-class correlation (ICC)). RESULTS: Comparing with adolescents born from Swedish mothers, all other children had a lower AAM use, especially those whose mothers were from upper middle- and low-income countries (OR = 0.47, 95% confidence interval: 0.35-0.61). However, the ICC was low (i.e., ICC ~ 3%) for both preventive and relief AAM. CONCLUSIONS: MCOB was associated to adolescent use of AAM. However, the small ICC indicates that MCOB is an inaccurate categorization for identifying inappropriate use of AAM among Swedish adolescents. PMID- 26553249 TI - Adverse lifestyle and health-related quality of life: gender differences in patients with and without chronic conditions. AB - OBJECTIVES: The aim was to investigate the relationship between the main lifestyle-related factors and health-related quality of life (HRQoL) in a sample of patients with and without chronic conditions (CCs) with respect to the gender differences in both groups. METHODS: A cross-sectional study was conducted on 1061 patients (of which 308 had no CCs and 753 of those had one or more CCs) recruited at primary health care centres and the Internal Medicine Clinic at Tartu University Hospital in Estonia. Data were collected during 2012-2014. The patient's age, self-reported smoking status, alcohol consumption (assessed by Alcohol Use Disorders Identification Test) and body mass index were used as independent variables to predict the physical component scores (PCS) and mental component scores (MCS) of HRQoL (assessed by SF-36). RESULTS: Smoking had a negative association with both physical and mental components of HRQoL only in women with CCs. Further, the PCS of chronically ill women was negatively associated with the higher body mass index. Harmful drinking had a negative association with the HRQoL in all patient groups, except with the PCS in women with CC. Light alcohol consumption without symptoms of harmful use or dependency had a positive association with the physical and mental HRQoL in all patient groups, except with the MCS in women without CCs. CONCLUSION: Adverse lifestyle had the most expressed association with HRQoL in women with CCs. Light alcohol consumption had a positive association, but harmful use of alcohol had an inverse association with HRQoL irrespective of patients' gender or health status. PMID- 26553250 TI - Psychological complaints among children in joint physical custody and other family types: Considering parental factors. AB - AIMS: Increasing proportions of Scandinavian children and children in other Western countries live in joint physical custody, moving between parents' homes when parents live apart. Children and parents in non-intact families are at risk of worse mental health. The potential influence of parental ill-health on child well-being in the context of differing living arrangements has not been studied thoroughly. This study investigates the psychological complaints of children in joint physical custody in comparison to children in sole parental care and nuclear families, while controlling for socioeconomic differences and parental ill-health. METHODS: Data were obtained from Statistics Sweden's yearly Survey of Living Conditions 2007-2011 and child supplements with children 10-18 years, living in households of adult participants. Children in joint physical custody (n=391) were compared with children in sole parental care (n=654) and children in nuclear families (n=3,639), using a scale of psychological complaints as the outcome measure. RESULTS: Multiple regression modelling showed that children in joint physical custody did not report higher levels of psychological complaints than those in nuclear families, while children in sole parental care reported elevated levels of complaints compared with those in joint physical custody. Adding socioeconomic variables and parental ill-health only marginally attenuated the coefficients for the living arrangement groups. Low parental education and parental worry/anxiety were however associated with higher levels of psychological complaints. CONCLUSIONS: Psychological complaints were lower among adolescents in joint physical custody than in adolescents in sole parental care. The difference was not explained by parental ill-health or socioeconomic variables. PMID- 26553252 TI - Heterogeneous Diastereoselective Catalysis--A Powerful Strategy Toward C(15) Stereoselectivity from PGF2alpha Analogues Structure. AB - A major trend in fine chemicals and pharmaceuticals is the synthesis of molecules with increased complexity. This trend translates the aim of organic syntheses to conditions in which high degrees of chemo-, regio- and stereoselectivity can be provided. In this context, the chemoselective hydrogenation of one functional group in the presence of other reactive groups is a frequently encountered problem in fine chemicals manufacture. This study provides a critical analysis including elegant examples of reactions in which high chemo- and diastereoselectivities were achieved in the hydrogenation of a C=O group in the presence of C=C double bond. A particular emphasis is addressed to the stereoselective C(15) synthesis from Cloprostenol--a PGF2alpha structural analogue. PMID- 26553251 TI - Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma. AB - BACKGROUND: Cell division cycle 5-like (Cdc5L), as a pre-mRNA splicing factor, is a regulator of mitotic progression. Previous study found that deletion of endogenous Cdc5L decreases the cell viability via dramatic mitotic arrest, while the role of Cdc5L in cancer biology remains under debate. AIMS: To investigate the involvement of Cdc5L in the progression of hepatocellular carcinoma (HCC). METHODS: In this study, the expression of Cdc5L was evaluated by Western blot in 8 paired fresh HCC tissues and immunohistochemistry on 116 paraffin-embedded slices. We treated HCC cells by nocodazole to analyze the role of Cdc5L in mitotic progress. To determine whether Cdc5L could regulate the proliferation of HCC cells, we increased endogenous Cdc5L and analyzed the proliferation of HCC cells using Western blot, CCK8, flow cytometry assays, and colony formation analyses. Furthermore, Cdc5L-siRNA oligos were used to confirm that Cdc5L plays an essential role in HCC development. RESULTS: Cdc5L was highly expressed in HCC and significantly associated with multiple clinicopathological factors, including AJCC stage, tumor size, and Ki-67. Besides, univariate and multivariate survival analyses demonstrated that high Cdc5L expression was an independent prognostic factor for HCC patients' poor survival. Overexpression of Cdc5L favors cell cycle progress of HCC cells, while downregulation of Cdc5L results in cell cycle arrest at G2/M phase and reduced cell proliferation of HCC cells. CONCLUSIONS: Our findings suggested that Cdc5L could play an important role in the tumorigenesis of HCC and thus be a potential therapeutical target to prevent HCC progression. PMID- 26553253 TI - Stereoselective Modulation of P-Glycoprotein by Chiral Small Molecules. AB - Inhibition of drug efflux pumps such as P-glycoprotein (P-gp) is an approach toward combating multidrug resistance, which is a significant hurdle in current cancer treatments. To address this, N-substituted aryloxymethyl pyrrolidines were designed and synthesized in their homochiral forms in order to investigate the stereochemical requirements for the binding site of P-gp. Our study provides evidence that the chiral property of molecules could be a strategy for improving the capacity for interacting with P-gp, as the most active compounds of the series stereoselectively modulated this efflux pump. The naphthalene-1-yl analogue (R)-2-[(2,3-dichlorophenoxy)methyl]-1-(naphthalen-1 ylmethyl)pyrrolidine) [(R)-7 a] emerged foremost for its potency and stereoselectivity toward P-gp, with the S enantiomer being nearly inactive. The modulation of P-gp by (R)-7 a involved consumption of ATP, thus demonstrating that the compound behaves as a P-gp substrate. PMID- 26553254 TI - Wear properties of dental ceramics and porcelains compared with human enamel. AB - STATEMENT OF PROBLEM: Contemporary pressable and computer-aided design/manufacturing (CAD/CAM) ceramics exhibit good mechanical and esthetic properties. Their wear resistance compared with human enamel and traditional gold based alloys needs to be better investigated. PURPOSE: The purpose of this in vitro study was to compare the 2-body wear resistance of human enamel, gold alloy, and 5 different dental ceramics, including a recently introduced zirconia reinforced lithium silicate ceramic (Celtra Duo). MATERIAL AND METHODS: Cylindrical specimens were fabricated from a Type III gold alloy (Aurocast8), 2 hot pressed ceramics (Imagine PressX, IPS e.max Press), 2 CAD/CAM ceramics (IPS e.max CAD, Celtra Duo), and a CAD/CAM feldspathic porcelain (Vitablocs Mark II) (n=10). Celtra Duo was tested both soon after grinding and after a subsequent glaze firing cycle. Ten flat human enamel specimens were used as the control group. All specimens were subjected to a 2-body wear test in a dual axis mastication simulator for 120000 loading cycles against yttria stabilized tetragonal zirconia polycrystal cusps. The wear resistance was analyzed by measuring the vertical substance loss (mm) and the volume loss (mm(3)). Antagonist wear (mm) was also recorded. Data were statistically analyzed with 1 way ANOVA tests (alpha=.05). RESULTS: The wear depth (0.223 mm) of gold alloy was the closest to that of human enamel (0.217 mm), with no significant difference (P>.05). The greatest wear was recorded on the milled Celtra Duo (wear depth=0.320 mm), which appeared significantly less wear resistant than gold alloy or human enamel (P<.05). CONCLUSIONS: The milled and not glazed Celtra Duo showed a small but significantly increased wear depth compared with Aurocast8 and human enamel. Wear depth and volumetric loss for the glaze-fired Celtra Duo and for the other tested ceramics did not statistically differ in comparison with the human enamel. PMID- 26553255 TI - In-office technique for selectively etching titanium abutments to improve bonding for interim implant prostheses. AB - A technique is described for increasing the surface area of a titanium abutment with hydrofluoric acid etching. This provides mechanical retention for acrylic resin and composite resins and can be easily and rapidly accomplished in both the laboratory and clinic. PMID- 26553256 TI - Influence of denture adhesives on occlusion and disocclusion times. AB - STATEMENT OF PROBLEM: The effectiveness of adhesives in enhancing several functional aspects of complete denture performance has been well established. The direct influence of adhesives on occlusal contact simultaneity has not yet been investigated. PURPOSE: The purpose of this crossover clinical trial was to evaluate quantitatively the influence of adhesives on occlusal balance by recording timed occlusal contacts; namely occlusion time (OT) and disocclusion time during right (DT-right) and left (DT-left) excursions by using computerized occlusal analysis. MATERIAL AND METHODS: A crossover clinical trial was adopted. Assessments were carried out while participants (n=49) wore their dentures first without then with adhesives. Computerized occlusal analysis using the T-Scan III system was conducted to perform baseline computer-guided occlusal adjustment for conventionally fabricated dentures. Retention and stability assessment using the modified Kapur index and recording of OT and DT-right and DT-left values using the T-Scan III were subsequently carried out for all dentures, first without adhesives and then after application of adhesive. All T-Scan procedures were carried out by the same clinician. Wilcoxon signed-rank test was used to analyze the Kapur index scores and occlusal parameters (alpha=.05). RESULTS: Stability and retention of conventional dentures ranged initially from good to very good. However, adhesive application resulted in significant improvement (P<.001) in stability and retention and a significant decrease in duration of all occlusal parameters (OT [P=.003], DT-right [P=.003], and DT-left [P=.008]). CONCLUSIONS: Adhesives significantly decreased OT and DT durations in initially well-fitting complete dentures with fairly well balanced occlusion, and further enhanced denture stability and occlusal contact simultaneity. PMID- 26553257 TI - The impact of allergic rhinitis on the management of asthma in a working population. AB - BACKGROUND: Currently, little data is available about the management of asthma in the working population. The aim of this study was to describe asthma control and severity among workers according to current or previous allergic rhinitis comorbidity. METHODS: A network of occupational physicians participated in this pilot study on a voluntary basis. They included a random sample of salaried workers during their systematic occupational medical check-up. All subjects completed a self-administered questionnaire based on the European Community Respiratory Health Survey screening questionnaire, and if they reported any respiratory symptoms including allergic rhinitis, the physician filled in a medical questionnaire. Current asthma control and severity were evaluated according to 2006 Global Initiative for Asthma guidelines. RESULTS: A total of 110 occupational physicians from two French regions participated. Out of the 6906 employees screened, 3102 identified respiratory symptoms and completed the medical questionnaire and performed spirometry. Overall, 374 were identified as current asthmatics, including 271 (72.5%) with allergic rhinitis. Among current asthmatics with current allergic rhinitis (n = 95), 68.8% had partially controlled asthma or uncontrolled asthma, including 51.6% who received insufficient anti-asthmatic treatment. Partly or no control asthma was not associated with current rhinitis (OR = 1.4; 95% CI: 0.8-2.7). Current asthmatics with current or previous allergic rhinitis had a significantly lower risk of emergency department visits than current asthmatics without allergic rhinitis (respectively 11.6, 17.1 and 29.1%; P = 0.002). CONCLUSIONS: Most current asthmatics both with and without allergic rhinitis had uncontrolled asthma, with inappropriate treatment. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace. PMID- 26553259 TI - Erratum to: The relationship of recombination rate, genome structure, and patterns of molecular evolution across angiosperms. PMID- 26553258 TI - Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study. AB - BACKGROUND: During the 2009 influenza A (H1N1) pandemic, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix(r)) was offered to the Norwegian population. The coverage among children reached 54%. Our aim was to estimate the risk of febrile seizure in children after exposure to pandemic influenza vaccination or infection. METHODS: The study population comprised 226,889 children born 2006-2009 resident in Norway per October 1st, 2009. Febrile seizure episodes were defined by emergency hospital admissions / emergency outpatient hospital care with International Classification of Diseases, Version 10, codes R56.0 or R56.8. The self-controlled case series method was applied to estimate incidence rate ratios (IRRs) in pre-defined risk periods compared to the background period. The total observation window was +/- 180 days from exposure day. Among 113,068 vaccinated children, 656 (0.6%) had at least one febrile seizure episode. RESULTS: The IRR of febrile seizures 1-3 days after vaccination was 2.00 (95% confidence interval [CI]: 1.15-3.51). In the period 4-7 days after vaccination, no increased risk was observed. Among the 8172 children diagnosed with pandemic influenza, 84 (1.0%) had at least one febrile seizure episode. The IRR of febrile seizures on the same day as a diagnosis of influenza was 116.70 (95% CI: 62.81-216.90). In the period 1-3 days after a diagnosis of influenza, a tenfold increased risk was observed (IRR 10.12, 95% CI: 3.82 - 26.82). CONCLUSIONS: In this large population-based study with precise timing of exposures and outcomes, we found a twofold increased risk of febrile seizures 1-3 days after pandemic influenza vaccination. However, we found that pandemic influenza infection was associated with a much stronger increase in risk of febrile seizures. PMID- 26553260 TI - Clinical and laboratory indicators of polycystic ovary syndrome in Chinese Han nationality with different Rotterdam criteria-based phenotypes. AB - The aim of this study was to investigate the clinical, endocrinic and metabolic indicators in polycystic ovary syndrome (PCOS) with different Rotterdam criteria (RC)-based subtypes, thus to guide the treatments. Six hundred and forty-seven PCOS cases were divided into four groups, with 60 cases set as the control group, the clinical and endocrinic indicators of different subtypes were evaluated. Group A was the most common and the most serious (63.2%), while group B was the least (9%). The clinical signs, as well as the endocrinic and metabolic characteristics, of the two groups were similar, but group A exhibited higher androgen level and hirsutism score. The phenotypes of group C (15.6%) and group D (12.9%) were mild, but compared with the control group, luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) were significantly increased. Insulin resistance in these four subtypes were positively correlated with apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1), while only positively correlated with serum total testosterone, and negatively correlated with LH/FSH in group A. RC-PCOS typing could reflect the basic characteristics of the disease. Hyperandrogenism was the main basis for distinguishing PCOS, although the non-hyperandrogenism group could represent a relatively mild phenotype of PCOS, there might exist different pathogenic pathways. PMID- 26553262 TI - Linalool Affects the Antimicrobial Efficacy of Essential Oils. AB - The high concentrations of essential oils are generally required to receive microbial purity of the products (cosmetics, medicine). On the other hand, their application due to the high concentration of essential oils may be limited by changes in organoleptic and textural quality of the products, as well as they cause irritation and allergies in users. Addition of linalool to essential oil may significantly enhance its antimicrobial effectiveness and reduce their concentrations in products, taking advantage of their synergistic and additive effects. The aim of the study was to compare antimicrobial activity of essential oil alone and in combination with linalool. The antimicrobial activity of the essential oil of Thymus vulgaris, Juniperus communis, Pelargonium graveolens, Citrus bergamia, Citrus grandis, Lavandula angustifolia, Cinnamomum zeylanicum, Melaleuca alternifolia, Syzygium aromaticum, linalool and their combination was investigated against bacteria and fungi using the disc diffusion method. The addition of linalool to S. aromaticum oil in a synergistic manner enhanced its antimicrobial efficacy against P. aeruginosa and A. brasiliensis. Moreover, the additive interaction between this oil and linalool was observed against S. aureus, E. coli and C. albicans. It was also found that linalool in an additive manner increased the antimicrobial effectiveness of T. vulgaris oil against P. aeruginosa. The antimicrobial properties of mixture of essential oils with their active constituents may be used for creating new strategies to maintain microbiological purity of products. PMID- 26553261 TI - Liver X Receptor Agonist Modifies the DNA Methylation Profile of Synapse and Neurogenesis-Related Genes in the Triple Transgenic Mouse Model of Alzheimer's Disease. AB - The liver X receptor agonist, GW3965, improves cognition in Alzheimer's disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50 mg/kg/day for 6 days). DNA methylation state was examined by modified bisulfite conversion and hybridization on Illumina Infinium Methylation BeadChip 450 k arrays. The Morris water maze was used for behavioral analysis. Our results show in addition to improvement in cognition methylation changes in 39 of 13,715 interrogated probes in treated 3xTg-AD mice compared with untreated 3xTg-AD mice. These changes in methylation probes include 29 gene loci. Importantly, changes in methylation status were mainly from synapse related genes (SYP, SYN1, and DLG3) and neurogenesis-associated genes (HMGB3 and RBBP7). Thus, our results indicate that liver X receptors (LXR) agonist treatment induces rapid changes in DNA methylation, particularly in loci associated with genes involved in neurogenesis and synaptic function. Our results suggest a new potential mechanism to explain the beneficial effect of GW3965. PMID- 26553263 TI - Development of a Real-Time Cell Analysing (RTCA) method as a fast and accurate screen for the selection of chikungunya virus replication inhibitors. AB - BACKGROUND: The xCELLigence real-time cell analysis (RTCA) system is an established electronic cell sensor array. This system uses microelectronic biosensor technology that is verified for real-time, label-free, dynamic and non offensive monitoring of cellular features, including detection of viral cytopathic effect (CPE). Screening viral replication inhibitors based on presence of CPE has been applied for different viruses, including chikungunya virus (CHIKV). However, most CPE-based methods, including MTT and MTS assays, do not provide information on the initiation of CPE nor the changes in reaction rate of the virus propagation over time. Therefore, in this study we developed an RTCA method as an accurate and time-based screen for antiviral compounds against CHIKV. METHODS: CHIKV-infected Vero cells were used as an in vitro model to establish the suitability of the RTCA system as a quantitative analysis method based on the induction of CPE. We also performed an MTS assay as a CPE-based conventional method. Experimental assays were carried out to evaluate the optimal seeding density of the Vero cells, cytotoxicity of the tested compounds, titration of CHIKV and the antiviral activity of ribavirin, which has been reported as an effective compound against CHIKV in vitro replication. RESULTS: The optimal time point for viral inoculation was 18 h after seeding the cells. We determined that the maximum non-toxic dose (MNTD) of ribavirin was 200 MUg/ml for Vero cells. Regarding the dynamic monitoring of Vero cell properties during antiviral assay, approximately 34 h post-infection, the normalised Cell Index (CI) values of CHIKV-infected Vero cells started to decrease, while the vehicle controls did not show any significant changes. We also successfully showed the dose dependent manner of ribavirin as an approved in vitro inhibitor for CHIKV through our RTCA experiment. CONCLUSION: RTCA technology could become the prevailing tool in antiviral research due to its accurate output and the opportunity to carry out quality control and technical optimisation. PMID- 26553264 TI - Pancreaticojejunostomy Stricture After Pancreatoduodenectomy: Outcomes After Operative Revision. AB - INTRODUCTION: The natural history of radiographic strictures of the pancreaticojejunostomy (PJ) after pancreatoduodenectomy (PD) is difficult to characterize. The purpose of this study was to identify the indications for operative revision of PJ strictures after PD for benign and malignant disease and to evaluate its safety and clinical efficacy. METHODS: A retrospective review of all patients undergoing operative revision of PJ strictures following PD at a single academic institution over an 8-year period (2006-2014) was performed. RESULTS: Twenty-seven patients underwent revision of a symptomatic radiographically detectable PJ stricture. The median time from PD to PJ stricture diagnosis was 46 months. The median increase in the main pancreatic duct diameter between the time of PD and PJ revision was 2 mm. The overall morbidity after PJ revision was 26 %. No postoperative mortality occurred. Twenty-one (78 %) patients experienced resolution of symptoms without recurrent acute pancreatitis after PJ revision during a median follow-up of 30 months. Durable symptom resolution was reported among 60 % of patients with chronic pancreatitis. CONCLUSIONS: Surgical revision of pancreaticojejunostomy strictures is technically safe and clinically effective for selected patients who experience recurrent acute pancreatitis after pancreatoduodenectomy for either benign or malignant disease. PMID- 26553266 TI - Giant Esophageal Lipoma. PMID- 26553265 TI - National Trends in Utilization of Endoscopic Ultrasound for Gastric Cancer: a SEER-Medicare Study. AB - INTRODUCTION: Accurate preoperative staging is important for patients with gastric cancer. This study identifies the rate of utilization of endoscopic ultrasound (EUS) and its associated factors in Medicare patients with gastric adenocarcinoma. METHODS: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims database was queried from 1996 to 2009 for patients with gastric cancer who underwent gastric resection. Analysis with univariate, multivariate, and Cochran-Armitage trend tests were performed. RESULTS: In 5826 patients with gastric cancer with an average age of 76.9 +/- 6.62 years, 59.1% had regionalized spread of cancer. EUS utilization increased significantly during the study period from 2.6% to 22% (p < 0.0001). EUS patients were more likely to be male, white, married, have higher education and income quartiles, and live in large metropolitan areas compared to non-EUS patients (p < 0.0001). Even after controlling for confounding factors, patients who underwent EUS were more likely to have >15 lymph nodes examined (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.04-1.53) and have the administration of both pre- and postoperative chemotherapy (OR 1.27, 95% CI 1.03-1.57). CONCLUSION: EUS is currently under utilized but increasing. Patients who underwent EUS (12.9%) were more likely to receive other NCCN-recommended care, including perioperative chemotherapy and adequate nodal retrieval. PMID- 26553267 TI - Metabolic Syndrome is Associated with Increased Postoperative Morbidity and Hospital Resource Utilization in Patients Undergoing Elective Pancreatectomy. AB - PURPOSE: In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy. METHODS: Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index >=30 kg/m(2), hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30 day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as >=13 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant). RESULTS: On univariate analysis, 1070 (6.8%) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P < 0.05 for all analyses). After controlling for potentially confounding variables, there was a 26% increased odds of postoperative morbidity (P < 0.001), 17% increased odds of major morbidity (P = 0.034), 32% increased odds of surgical site infection (P < 0.001), 34% increased odds of respiratory failure (P = 0.023), 68% increased odds of pulmonary embolism (P = 0.045), 26% increased odds of blood transfusion (P = 0.018), and 21% increased odds of prolonged hospital stay (P = 0.011) in patients with MS compared to patients without MS. MS was not associated with 30-day mortality after elective pancreatectomy (P = 0.465). When stratified by distal versus proximal pancreatectomy and benign versus malignant disease, the effect of MS on outcomes appears to be modified by type of pancreatectomy and indication with poorer outcomes observed for distal pancreatectomies and benign indications for resection. CONCLUSION: MS is an under-emphasized predictor of increased postoperative morbidity and utilization of hospital resources in patients undergoing elective pancreatectomy. The effect of MS on these postoperative outcomes appears to be more pronounced for patients with benign rather than malignant indications for pancreatectomy and in patients undergoing distal rather than proximal pancreatectomy. These results may inform patient selection, optimization of comorbidities prior to elective pancreatectomy, and strategies for postoperative management. PMID- 26553268 TI - Interpretation of Abdominal CT Findings in Patients Who Develop Acute on Chronic Mesenteric Ischemia. AB - BACKGROUND: We studied whether ischemia-specific computed tomography (CT) findings are consistently detectable in patients who develop acute on chronic mesenteric ischemia (AOCMI), whereas absent in chronic mesenteric ischemia (CMI). METHODS: Consecutive patients with symptomatic angiography-verified atherosclerotic obstruction of the superior mesenteric artery (SMA) were categorized as AOCMI (n = 27) or CMI (n = 20). Three experienced radiologists blindly evaluated the contrast-enhanced CTs for vascular and intestinal findings. Kappa statistics was used to test interobserver agreement. RESULTS: Two observers had substantial agreement (k = 0.66) that two thirds of AOCMI patients showed ischemia-specific CT findings (decreased bowel wall enhancement, pneumatosis, or thrombotic SMA clot); the third observer agreed only fairly regarding pneumatosis and thrombosis (k = 0.3-0.4). All observers had substantial agreement (k = 0.65 0.71) that most patients with AOCMI had unspecific intestinal findings such as mesenteric fat stranding in up to 96%, bowel lumen dilatation in 93%, and bowel wall thickening in 70%, while only few patients with CMI had such findings (due to chronic ischemic colitis) (P < 0.001). CONCLUSION: One third of AOCMI patients presented without any ischemia-specific CT signs. However, any intestinal abnormality in CT together with SMA obstruction should raise suspicion of intestinal ischemia. Furthermore, clinicians need to be aware of the interobserver variability in the CT interpretation. PMID- 26553269 TI - Spanish Pacemaker Registry. Twelfth Official Report of the Spanish Society of Cardiology Working Group on Cardiac Pacing (2014). AB - INTRODUCTION AND OBJECTIVES: This report describes the results of the analysis of pacemaker implant and replacement data submitted to the Spanish Pacemaker Registry in 2014, with special reference to pacing mode selection. METHODS: The report is based on the processing of information provided by the European Pacemaker Patient Identification Card. RESULTS: Information was received from 117 hospitals, with a total of 12 358 cards, representing 34% of estimated activity. Use of conventional generators and resynchronization devices was 784 and 64.4 units per million population, respectively. The mean age of patients receiving an implant was 77.3 years. Men received 59% of implants and 56.4% of replacements. Most patients receiving generator implants and replacements were in the age range 80 to 89 years. Most endocardial leads used were bipolar, and 84.2% had an active fixation system. Pacing was in VVI/R mode despite being in sinus rhythm in 24.7% of patients with sick sinus syndrome and 24% of those with atrioventricular block. CONCLUSIONS: The use of pacemaker generators and resynchronization devices per million population continued to increase. Most implanted leads had active fixation and approximately 20% had magnetic resonance imaging protection. Age and sex directly influenced pacing mode selection, which could have been improved in more than 20% of cases. PMID- 26553270 TI - Surface coating of siRNA-peptidomimetic nano-self-assemblies with anionic lipid bilayers: enhanced gene silencing and reduced adverse effects in vitro. AB - Cationic vectors have demonstrated the potential to facilitate intracellular delivery of therapeutic oligonucleotides. However, enhanced transfection efficiency is usually associated with adverse effects, which also proves to be a challenge for vectors based on cationic peptides. In this study a series of proteolytically stable palmitoylated alpha-peptide/beta-peptoid peptidomimetics with a systematically varied number of repeating lysine and homoarginine residues was shown to self-assemble with small interfering RNA (siRNA). The resulting well defined nanocomplexes were coated with anionic lipids giving rise to net anionic liposomes. These complexes and the corresponding liposomes were optimized towards efficient gene silencing and low adverse effects. The optimal anionic liposomes mediated a high silencing effect, which was comparable to that of the control (cationic Lipofectamine 2000), and did not display any noticeable cytotoxicity and immunogenicity in vitro. In contrast, the corresponding nanocomplexes mediated a reduced silencing effect with a more narrow safety window. The surface coating with anionic lipid bilayers led to partial decomplexation of the siRNA peptidomimetic nanocomplex core of the liposomes, which facilitated siRNA release. Additionally, the optimal anionic liposomes showed efficient intracellular uptake and endosomal escape. Therefore, these findings suggest that a more efficacious and safe formulation can be achieved by surface coating of the siRNA-peptidomimetic nano-self-assemblies with anionic lipid bilayers. PMID- 26553271 TI - The effect of orthographic and emotional neighbourhood in a colour categorization task. AB - This study investigated whether and how the strength of reading interference in a colour categorization task can be influenced by lexical competition and the emotional characteristics of words not directly presented. Previous findings showed inhibitory effects of high-frequency orthographic and emotional neighbourhood in the lexical decision task. Here, we examined the effect of orthographic neighbour frequency according to the emotional valence of the higher frequency neighbour in an emotional orthographic Stroop paradigm. Stimuli were coloured neutral words that had either (1) no orthographic neighbour (e.g. PISTIL [pistil]), (2) one neutral higher-frequency neighbour (e.g. tirade [tirade]/TIRAGE [draw]) or (3) one negative higher-frequency neighbour (e.g. idiome [idiom]/IDIOTE [idiotic]). The results showed that colour categorization times were longer for words with no orthographic neighbour than for words with one neutral neighbour of higher frequency and even longer when the higher frequency neighbour was neutral rather than negative. Thus, it appears not only that the orthographic neighbourhood of the coloured stimulus words intervenes in a colour categorization task, but also that the emotional content of the neighbour contributes to response times. These findings are discussed in terms of lexical competition between the stimulus word and non-presented orthographic neighbours, which in turn would modify the strength of reading interference on colour categorization times. PMID- 26553272 TI - When looking back to nothing goes back to nothing. AB - Previous research showed that the eyes revisit the location in which the stimulus has been encoded when visual or verbal information is retrieved from memory. A recent study showed that this behavior still occurs 1 week after encoding, suggesting that visual, spatial and linguistic information is tightly associated with the oculomotor trace and stored as an integrated memory representation. However, it is yet unclear whether looking behavior simply remains stable between encoding and recall or whether it changes over time in a more fine-tuned manner. Here, we investigate the time course of looking behavior during recall in multiple sessions across 1 week. Participants encoded visual objects presented in one of the four locations on the computer screen. In five sessions during the week after encoding, they performed on a visual memory recall task. During retrieval, participants looked back to the encoding location, but only in the recall sessions within 1 day of encoding. We discuss different explanations for the temporal dynamics of looking behavior during recall, searching for the role of eye movements in memory. PMID- 26553273 TI - Metabolic Modeling of Dynamic (13)C NMR Isotopomer Data in the Brain In Vivo: Fast Screening of Metabolic Models Using Automated Generation of Differential Equations. AB - Most current brain metabolic models are not capable of taking into account the dynamic isotopomer information available from fine structure multiplets in (13)C spectra, due to the difficulty of implementing such models. Here we present a new approach that allows automatic implementation of multi-compartment metabolic models capable of fitting any number of (13)C isotopomer curves in the brain. The new automated approach also makes it possible to quickly modify and test new models to best describe the experimental data. We demonstrate the power of the new approach by testing the effect of adding separate pyruvate pools in astrocytes and neurons, and adding a vesicular neuronal glutamate pool. Including both changes reduced the global fit residual by half and pointed to dilution of label prior to entry into the astrocytic TCA cycle as the main source of glutamine dilution. The glutamate-glutamine cycle rate was particularly sensitive to changes in the model. PMID- 26553274 TI - Morphometric analysis of sex differences in contemporary Japanese pelves using multidetector computed tomography. AB - Sex estimation of decomposed or skeletal remains is clearly important in forensic contexts. Recently, contemporary population-specific data has been obtained using multidetector computed tomography (MDCT) scanning. The main purpose of this study was to investigate skeletal pelvic dimorphism in a contemporary Japanese forensic sample and to quantify the accuracy of sex estimation using various pelvic measurements obtained from three-dimensional (3D) CT images. This study used a total of 208 cadavers (104 males, 104 females) of which postmortem CT scanning and subsequent forensic autopsy were conducted between December 2011 and August 2014. Eleven measurements of each pelvis were obtained from 3D CT reconstructed images that extracted only bone data. The measurements were analyzed using descriptive statistics and discriminant function analyses. All except one measurement were dimorphic in terms of sex differences. Univariate discriminant function analyses using these measurements provided sex classification accuracy rates of 62.0-98.1%. The subpubic angle was found to contribute most significantly to accurate sex estimation. Multivariate discriminant functions yielded sex prediction accuracy rates of 63.9-98.1%. In conclusion, the pelvic measurements obtained from 3D CT images of a contemporary Japanese population successfully demonstrated sexual dimorphism and may be useful for the estimation of skeletal sex in the field of forensic anthropology. PMID- 26553275 TI - The experience of caring for patients with dementia within a general hospital setting: a meta-synthesis of the qualitative literature. AB - OBJECTIVES: The optimal care of people with dementia in general hospitals has become a policy and practice imperative over recent years. However, despite this emphasis, the everyday experience of staff caring for this patient group is poorly understood. This review aimed to synthesise the findings from recent qualitative studies in this topic published prior to January 2014 to develop knowledge and provide a framework to help inform future training needs. METHOD: A systematic search of the literature was conducted across five academic databases and inclusion/exclusion criteria applied to the retrieved papers. A meta ethnographic approach was utilised to synthesise the resulting 14 qualitative papers. RESULTS: Five key themes were constructed from the findings: overcoming uncertainty in care; constraints of the environmental and wider organisational context; inequality of care; recognising the benefits of person-centred care; and identifying the need for training. These themes explore the opportunities and challenges associated with caring for this group of patients, as well as suggestions to improve staff experiences and patient care. CONCLUSION: The synthesis highlighted a lack of knowledge and understanding of dementia within general hospital staff, particularly with regard to communication with patients and managing behaviours that are considered challenging. This limited understanding, coupled with organisational constraints on a busy hospital ward, contributed to low staff confidence, negative attitudes towards patients with dementia and an inability to provide person-centred care. The benefits of dementia training for both ward staff and hospital management and peer discussion/support for ward staff are discussed. PMID- 26553276 TI - A Newly Identified Missense Mutation in FARS2 Causes Autosomal-Recessive Spastic Paraplegia. AB - Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by spasticity of the lower limbs due to pyramidal tract dysfunction. Here, we report that a missense homozygous mutation c.424G>T (p.D142Y) in the FARS2 gene, which encodes a mitochondrial phenylalanyl tRNA synthetase (mtPheRS), causes HSP in a Chinese consanguineous family by using combination of homozygous mapping and whole-exome sequencing. Immunohistochemical experiments were performed showing that the FARS2 protein was highly expressed in the Purkinje cells of rat cerebellum. The aminoacylation activity of mtPheRS was severely disrupted by the p.D142Y substitution in vitro not only in the first aminoacylation step but also in the last transfer step. Taken together, our results indicate that a missense mutation in FARS2 contributes to HSP, which has the clinical significance of the regulation of tRNA synthetases in human neurodegenerative diseases. PMID- 26553277 TI - In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning. AB - Intravenous lipid emulsion (ILE), a component of parenteral nutrition, consists of a fat emulsion of soy bean oil, egg phospholipids, and glycerin. Case reports suggest that ILE may reverse hypotension caused by acute poisoning with lipophilic drugs such as verapamil, but the mechanism remains unclear. The methods used are the following: (1) measurement of ILE concentration in serum samples from a patient with verapamil poisoning treated with ILE, (2) measurement of free verapamil concentrations in human serum mixed in vitro with increasing concentrations of ILE, and (3) measurement of murine ventricular cardiomyocyte L type Ca(2+) currents, intracellular Ca(2+), and contractility in response to verapamil and/or ILE. Maximum patient serum ILE concentration after infusion of 1 L ILE over 1 h was approximately 1.6 vol%. In vitro GC/MS verapamil assays showed that addition of ILE (0.03-5.0 vol%) dose-dependently decreased the free verapamil concentration in human serum. In voltage-clamped myocytes, adding ILE to Tyrode's solution containing 5 MUM verapamil recovered L-type Ca(2+) currents (ICa). Recovery was concentration dependent, with significant ICa recovery at ILE concentrations as low as 0.03 vol%. ILE had no effect on ICa in the absence of verapamil. In field-stimulated intact ventricular myocytes exposed to verapamil, adding ILE (0.5 %) resulted in a rapid and nearly complete recovery of myocyte contractility and intracellular Ca(2+). Our in vitro studies indicate that ILE acts as a lipid sink that rapidly reverses impaired cardiomyocyte contractility in the continued presence of verapamil. PMID- 26553278 TI - Bench to Bedside: From the Science to the Practice of Addiction Medicine. AB - The current understanding of addiction is based on a biopsychosocial model of illness. From a neurobiological perspective, addiction can be seen as the hijacking of the pleasure-reward pathways of the brain with a concomitant weakening of its executive function. The fundamental model has been expanded to include newer concepts such as multiple levels of severity of illness, motivational circuitry, and anti-reward pathways. These neurobiological concepts can explain some of the successes and failures of addiction treatment in the second half of the 20th century and the beginning of the 21st century. Psychosocial interventions (primarily cognitive behavior therapy, mutual help groups, and motivational interviewing) and pharmacological treatments (such as agonists, antagonists, and partial agonists) form the basis of addiction treatment today. PMID- 26553279 TI - Recognition and Knowledge of Medications with Black Box Warnings Among Pediatricians and Emergency Physicians. AB - "Boxed warnings" (BW), sometimes referred to as "black box warnings," are the most serious level of warning provided by the Food and Drug Administration (FDA). We aimed to assess physician awareness and knowledge of BW, and to gain a better understanding of where physicians obtain information about serious adverse drug reactions for commonly prescribed medications. A cross-sectional survey instrument was administered to emergency medicine (EM) and pediatrician (Peds) attending and resident physicians. The main outcome measures were physician performance in identifying medications with and without black box warnings and the content of the warnings. The survey response rate was 81/198 (41 %). Respondents correctly identified medications with BW only 36.3 % of the time, but were able to correctly identify medications without such warnings 83.8 % of the time. Attending physicians were better able to identify medications with or without BW when compared with residents (p < 0.05). Among residents, there was a statistically significant increase in the ability to identify medications with or without BW with increasing year of training (p < 0.01). Correct identification of the content of BW was low in both groups (13.3 %). Only 19/50 (37 %) EM physicians and 16/31 (52 %) Peds reported that they consider BW when prescribing medications. 23/81 (29 %) respondents indicated that they did not stay current or had no method of staying current with black box information. EM and Peds attending and resident physicians at a single institution had limited ability to identify medications containing BW or the content of such warnings. A significant number reported that they did not stay current or had no consistent method for staying current with BW. PMID- 26553281 TI - American College of Medical Toxicology Code of Ethics for Medical Toxicologists. PMID- 26553280 TI - Use of a Rapid Ethylene Glycol Assay: a 4-Year Retrospective Study at an Academic Medical Center. AB - Ethylene glycol (EG) is a common cause of toxic ingestions. Gas chromatography (GC)-based laboratory assays are the gold standard for diagnosing EG intoxication. However, GC requires specialized instrumentation and technical expertise that limits feasibility for many clinical laboratories. The objective of this retrospective study was to determine the utility of incorporating a rapid EG assay for management of cases with suspected EG poisoning. The University of Iowa Hospitals and Clinics core clinical laboratory adapted a veterinary EG assay (Catachem, Inc.) for the Roche Diagnostics cobas 8000 c502 analyzer and incorporated this assay in an osmolal gap-based algorithm for potential toxic alcohol/glycol ingestions. The main limitation is that high concentrations of propylene glycol (PG), while readily identifiable by reaction rate kinetics, can interfere with EG measurement. The clinical laboratory had the ability to perform GC for EG and PG, if needed. A total of 222 rapid EG and 24 EG/PG GC analyses were documented in 106 patient encounters. Of ten confirmed EG ingestions, eight cases were managed entirely with the rapid EG assay. PG interference was evident in 25 samples, leading to 8 GC analyses to rule out the presence of EG. Chart review of cases with negative rapid EG assay results showed no evidence of false negatives. The results of this study highlight the use of incorporating a rapid EG assay for the diagnosis and management of suspected EG toxicity by decreasing the reliance on GC. Future improvements would involve rapid EG assays that completely avoid interference by PG. PMID- 26553282 TI - Clinically Inconsequential Alerts: The Characteristics of Opioid Drug Alerts and Their Utility in Preventing Adverse Drug Events in the Emergency Department. AB - STUDY OBJECTIVE: We examine the characteristics of clinical decision support alerts triggered when opioids are prescribed, including alert type, override rates, adverse drug events associated with opioids, and preventable adverse drug events. METHODS: This was a retrospective chart review study assessing adverse drug event occurrences for emergency department (ED) visits in a large urban academic medical center using a commercial electronic health record system with clinical decision support. Participants include those aged 18 to 89 years who arrived to the ED every fifth day between September 2012 and January 2013. The main outcome was characteristics of opioid drug alerts, including alert type, override rates, opioid-related adverse drug events, and adverse drug event preventability by clinical decision support. RESULTS: Opioid drug alerts were more likely to be overridden than nonopioid alerts (relative risk 1.35; 95% confidence interval [CI] 1.21 to 1.50). Opioid drug-allergy alerts were twice as likely to be overridden (relative risk 2.24; 95% CI 1.74 to 2.89). Opioid duplicate therapy alerts were 1.57 times as likely to be overridden (95% CI 1.30 to 1.89). Fourteen of 4,581 patients experienced an adverse drug event (0.31%; 95% CI 0.15% to 0.47%), and 8 were due to opioids (57.1%). None of the adverse drug events were preventable by clinical decision support. However, 46 alerts were accepted for 38 patients that averted a potential adverse drug event. Overall, 98.9% of opioid alerts did not result in an actual or averted adverse drug event, and 96.3% of opioid alerts were overridden. CONCLUSION: Overridden opioid alerts did not result in adverse drug events. Clinical decision support successfully prevented adverse drug events at the expense of generating a large volume of inconsequential alerts. To prevent 1 adverse drug event, providers dealt with more than 123 unnecessary alerts. It is essential to refine clinical decision support alerting systems to eliminate inconsequential alerts to prevent alert fatigue and maintain patient safety. PMID- 26553283 TI - Mussel processing wastewater: a low-cost substrate for the production of astaxanthin by Xanthophyllomyces dendrorhous. AB - BACKGROUND: The use of astaxanthin in different industries such as the chemical, pharmaceutical, food, animal feed and cosmetic has been receiving increasing attention in recent years. Natural supplies of the pigment include crustacean by products, algal, and microbial cultivation, being the yeast Xanthophyllomyces dendrorhous together with the alga Haematococcus pluvialis the most promising microorganisms for this bioproduction. Different vegetable by-products of the food industry have been explored so far as low-cost substrates for the production of astaxanthin by X. dendrorhous. This study focuses for the first time on the use of a low-cost formulated medium from a marine by-product, mussel-processing wastewater, for the production of astaxanthin by the yeast X. dendrorhous. RESULTS: The yeast was able to grow in non-saccharified mussel broth, revealing the ability of the microorganism to hydrolyze glycogen. However, partial glycogen saccharification with alpha-amylase was needed for astaxanthin biosynthesis, obtaining maximal productions of 22.5-26.0 mg/L towards the end of the culture and coinciding with yeast highest amylolytic activity. Cultivations in totally saccharified media revealed an increase in maximal cell concentrations and a decrease in maximal growth rates and astaxanthin production with increasing glucose initial concentration. CONCLUSIONS: Astaxanthin production was higher in partially-saccharified mussel-processing waste than in synthetic medium (yeast peptone dextrose) containing glucose as carbon source (13 mg/L), suggesting this by-product is a promising nutritive medium for astaxanthin production. The use of this effluent also contributes towards the recycling and depuration of this highly pollutant effluent. PMID- 26553284 TI - Feasibility of a computer-assisted alcohol screening, brief intervention and referral to treatment program for DWI offenders. AB - BACKGROUND: Alcohol use patterns that are hazardous for one's health is prevalent among DWI (driving while intoxicated) offenders and is a key predictor of recidivism. The aim of this program evaluation was to determine the feasibility and usability of implementing a computer-assisted screening, brief intervention and referral to treatment (SBIRT) program for DWI offenders to enable the identification of those in need of treatment services soon after arrest. Our treatment program consisted of a web-based, self-guided screening tool for assessing alcohol use patterns and generating a personalized feedback report that is then used to deliver a brief motivational intervention and if needed, a referral to treatment. METHODS: Between August and November 2014, all DWI offenders attending orientation for pre-trial supervision were assessed for eligibility. Of the 129 eligible offenders, 53.5 percent enrolled and the first 50 were asked to complete a usability and satisfaction questionnaire. RESULTS: The results demonstrated that the majority of those screened reported at-risk alcohol use patterns requiring referral to treatment. Clients reported high ratings of usability and satisfaction with the screening tool and personalized feedback report, which did not significantly differ depending on alcohol use patterns. There were relatively few technical difficulties, and the majority of clients reported high levels of satisfaction with the overall SBIRT program. CONCLUSION: Results of this program evaluation suggest that computer-assisted SBIRT may be successfully implemented within the criminal justice system to DWI offenders soon after arrest; however, further research is required to examine its effects on treatment utilization and recidivism. PMID- 26553285 TI - Corpus callosotomy. AB - BACKGROUND: Corpus callosotomy is an effective, relatively low-risk, palliative procedure for a selected population of patients with medically intractable epilepsy. Here we describe this technique. METHOD: An interhemispheric microsurgical approach is performed. Neuronavigation facilitates orientation. The callosal body is transected through to the roof of the ipsilateral ventricle using an ultrasonic aspirator; the genu and rostrum are then identified and also split. If a total callosotomy is performed, transection of the splenium is performed with care given to preserve the crus of the fornix. CONCLUSIONS: Meticulous microsurgical technique and knowledge of the limbic system's anatomy is essential to keeping this procedure safe and effective. PMID- 26553286 TI - Merging carbohydrate chemistry with lectin histochemistry to study inhibition of lectin binding by glycoclusters in the natural tissue context. AB - Recognition of glycans by lectins leads to cell adhesion and growth regulation. The specificity and selectivity of this process are determined by carbohydrate structure (sequence and shape) and topology of its presentation. The synthesis of (neo)glycoconjugates with bi- to oligo-valency (glycoclusters) affords tools to delineate structure-activity relationships by blocking lectin binding to an artificial matrix, often a glycoprotein, or cultured cell lines. The drawback of these assays is that glycan presentation is different from that in tissues. In order to approach the natural context, we here introduce lectin histochemistry on fixed tissue sections to determine the susceptibility of binding of two plant lectins, i.e., GSA-II and WGA, to a series of 10 glycoclusters. Besides valency, this panel covers changes in the anomeric position (alpha/beta) and the atom at the glycosidic linkage (O/S). Flanked by cell and solid-phase assays with human tumor lines and two mucins, respectively, staining (intensity and profile) was analyzed in sections of murine jejunum, stomach and epididymis as a function of glycocluster presence. The marked and differential sensitivity of signal generation to structural aspects of the glycoclusters proves the applicability of this method. This enables comparisons between data sets obtained by using (neo)glycoconjugates, cells and the tissue context as platforms. The special advantage of processing tissue sections is the monitoring of interference with lectin association at sites that are relevant for functionality. Testing glycoclusters in lectin histochemistry will especially be attractive in cases of multi-target recognition (glycans, proteins and lipids) by a tissue lectin. PMID- 26553287 TI - Interval analysis of interictal EEG: pathology of the alpha rhythm in focal epilepsy. AB - The contemporary use of interictal scalp electroencephalography (EEG) in the context of focal epilepsy workup relies on the visual identification of interictal epileptiform discharges. The high-specificity performance of this marker comes, however, at a cost of only moderate sensitivity. Zero-crossing interval analysis is an alternative to Fourier analysis for the assessment of the rhythmic component of EEG signals. We applied this method to standard EEG recordings of 78 patients divided into 4 subgroups: temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), psychogenic nonepileptic seizures (PNES) and nonepileptic patients with headache. Interval-analysis based markers were capable of effectively discriminating patients with epilepsy from those in control subgroups (AUC~0.8) with diagnostic sensitivity potentially exceeding that of visual analysis. The identified putative epilepsy-specific markers were sensitive to the properties of the alpha rhythm and displayed weak or non-significant dependences on the number of antiepileptic drugs (AEDs) taken by the patients. Significant AED-related effects were concentrated in the theta interval range and an associated marker allowed for identification of patients on AED polytherapy (AUC~0.9). Interval analysis may thus, in perspective, increase the diagnostic yield of interictal scalp EEG. Our findings point to the possible existence of alpha rhythm abnormalities in patients with epilepsy. PMID- 26553288 TI - Outcomes of endopyelotomy for pelviureteric junction obstruction in the paediatric population: A systematic review. AB - INTRODUCTION: Dismembered pyeloplasty is the gold standard treatment for pelviureteric obstruction (PUJO) although endourological techniques are also employed. Outcomes and success rates for paediatric endopyelotomy are variably reported. OBJECTIVE: The study aimed to systematically analyse published literature to give an overall success rate for endopyelotomy in children. STUDY DESIGN: Medline and Embase databases were searched using relevant key terms to identify reports of paediatric endoplyelotomy. Literature reviews, case reports, series of <3 children and adult studies (age >20 years) were excluded. Primary and secondary procedures were considered separately. The procedure was considered successful if [a] the author reported success AND [b] there was no immediate conversion to open pyeloplasty OR a subsequent procedure to the PUJ 3 or more weeks after endopyelotomy. RESULTS: One hundred and fourteen studies were assessed, 15 were included in the final review. Overall, 220 endopyelotomies were performed in 216 patients; 128 had primary PUJO, 92 underwent secondary endopyelotomy. Median success rate was 71% (range 46-100) in the primary group and 75% (25-100) in the secondary group. Previously undetected crossing vessels were found at subsequent open pyeloplasty in 12 failures (11 primary = 31% of failed primary endopyelotomies). Complications were reported in 14.8% of primary and 14.1% of secondary procedures. DISCUSSION: This study is limited by the data given in the individual series: varied criteria used for patient selection and outcome as well as inconsistent pre and post operative imaging data precluded a meta-analysis. Designating procedures as failures if there were subsequent procedures to the PUJ lowered success rates from author-given figures for some studies. Complications rates after endopyelotomy are higher than those for open and minimally invasive pyeloplasty. Success rates for endoplyelotomy do not compare favourably with pyeloplasty and crossing vessels should be excluded before considering the procedure. PMID- 26553289 TI - Quantitation of Albumin in Serum Using "Turn-on" Fluorescent Probe with Aggregation-Enhanced Emission Characteristics. AB - An aggregation-enhanced emission active luminogen named as sodium 4,4'4"-(3,4 diphenyl-1H-pyrrole-1,2,5-triyl)tribenzoate (DP-TPPNa) with propeller construction was synthesized and developed as a "turn on" fluorescent probe for in situ quantitation of albumin in blood serum. The DP-TPPNa fluorescence intensity was linearly correlated with the concentration of two serum albumins, bovine serum albumin (BSA) and human serum albumin (HSA), in pure PBS buffer in the ranges of 2.18-70 and 1.68-100 MUg/mL, respectively. The detection limits were as low as 2.18 MUg/mL for BSA and 1.68 MUg/mL for HSA. The response time of fluorescence to serum albumin (SA) was very short (below 6 s), which achieved real-time detection. It also showed high selectivity to SA because other components in serum barely interfere with the detection of DP-TPPNa to SA, enabling in situ quantitative detection of SA without isolation from serum. DP TPPNa was successfully applied for the quantitative detection of BSA in fetal bovine serum. The mechanism of fluorescent turn-on behavior was elucidated utilizing an unfolding process induced by guanidine hydrochloride, which revealed a capture process via selective hydrophobic interaction and hydrogen bonding between luminogen and SA. PMID- 26553290 TI - Adverse Childhood Experiences and Alcohol Consumption in Midlife and Early Old Age. AB - AIMS: To examine the individual and cumulative effects of adverse childhood experiences (ACEs) on alcohol consumption in midlife and early old-age, and the role of ACEs in 10-year drinking trajectories across midlife. METHODS: Data were from the Whitehall II study, a longitudinal British civil service-based cohort study (N = 7870, 69.5% male). Multinomial logistic regression was used to examine the individual and cumulative effects of ACEs on weekly alcohol consumption. Mixed-effect multilevel modelling was used to explore the relationship between ACEs and change in alcohol consumption longitudinally. RESULTS: Participants who were exposed to parental arguments/fights in childhood were 1.24 (95% CI 1.06, 1.45) times more likely to drink at hazardous levels in midlife (mean age 56 years) after controlling for covariates and other ACEs. For each additional exposure to an ACE, the risk of hazardous drinking versus moderate drinking was increased by 1.12 (95% CI 1.03, 1.21) after adjusting for sex, age, adult socio economic status, ethnicity and marital status. No associations between ACEs and increased risk of hazardous drinking in early old-age (mean age 66 years) were found. In longitudinal analyses, ACEs did not significantly influence 10-year drinking trajectories across midlife. CONCLUSION: The effect of exposure to parental arguments on hazardous drinking persists into midlife. PMID- 26553291 TI - Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer. AB - BACKGROUND: The enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking. METHODS: 119 primary CRCs were analyzed. SNP was evaluated by real-time PCR from colonic healthy tissue, while EZH2 and H3K27me3 expression were studied by immunohistochemistry. We primarily looked for correlation between EZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features or KRAS exon 2 and BRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA. RESULTS: The C/C genotype was significantly associated with higher EZH2 (100 vs. 44 %; P = 0.019) and H3K27me3 (100 vs. 38 %; P = 0.009) staining intensity compared with C/T and T/T. EZH2 3+ staining significantly correlated with stronger H3K27me3 expression (P = 0.039). KRAS and BRAF mutations were not associated with EZH2 or H3K27me3 expression. CONCLUSION: EZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing. PMID- 26553292 TI - Ivermectin Pharmacokinetics, Metabolism, and Tissue/Egg Residue Profiles in Laying Hens. AB - The goals were to determine the ivermectin (IVM) plasma pharmacokinetics, tissue and egg residue profiles, and in vitro metabolism in laying hens. Experiments conducted were (1) 8 hens were intravenously treated with IVM and blood samples taken; (2) 88 hens were treated with IVM administered daily in water (5 days) (40 were kept and their daily eggs collected; 48 were sacrificed in groups (n = 8) at different times and tissue samples taken and analyzed); (3) IVM biotransformation was studied in liver microsomes. Pharmacokinetic parameters were AUC = 85.1 ng.day/mL, Vdss = 4.43 L/kg, and T1/2el = 1.73 days. Low IVM tissue residues were quantified with the highest measured in liver and skin+fat. IVM residues were not found in egg white, but significant amounts were quantified in yolk. Residues measured in eggs were greater than some MRL values, suggesting that a withdrawal period would be necessary for eggs after IVM use in laying hens. PMID- 26553293 TI - Electroencephalographic neurofeedback: Level of evidence in mental and brain disorders and suggestions for good clinical practice. AB - The technique of electroencephalographic neurofeedback (EEG NF) emerged in the 1970s and is a technique that measures a subject's EEG signal, processes it in real time, extracts a parameter of interest and presents this information in visual or auditory form. The goal is to effectuate a behavioural modification by modulating brain activity. The EEG NF opens new therapeutic possibilities in the fields of psychiatry and neurology. However, the development of EEG NF in clinical practice requires (i) a good level of evidence of therapeutic efficacy of this technique, (ii) a good practice guide for this technique. Firstly, this article investigates selected trials with the following criteria: study design with controlled, randomized, and open or blind protocol, primary endpoint related to the mental and brain disorders treated and assessed with standardized measurement tools, identifiable EEG neurophysiological targets, underpinned by pathophysiological relevance. Trials were found for: epilepsies, migraine, stroke, chronic insomnia, attentional-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, major depressive disorder, anxiety disorders, addictive disorders, psychotic disorders. Secondly, this article investigates the principles of neurofeedback therapy in line with learning theory. Different underlying therapeutic models are presented didactically between two continua: a continuum between implicit and explicit learning and a continuum between the biomedical model (centred on "the disease") and integrative biopsychosocial model of health (centred on "the illness"). The main relevant learning model is to link neurofeedback therapy with the field of cognitive remediation techniques. The methodological specificity of neurofeedback is to be guided by biologically relevant neurophysiological parameters. Guidelines for good clinical practice of EEG NF concerning technical issues of electrophysiology and of learning are suggested. These require validation by institutional structures for the clinical practice of EEG NF. PMID- 26553295 TI - Synanthropic Cockroaches (Blattidae: Periplaneta spp.) Harbor Pathogenic Leptospira in Colombia. AB - Leptospirosis cases in Colombia are typically linked to peridomestic rodents; however, empirical data suggest that Leptospira-infected patients with no apparent exposure to these reservoirs are common. Cockroaches (Periplaneta spp.) have equal or greater interaction with humans than rodents, yet their potential role as carriers of Leptospira has not been assessed. We determined if pathogenic Leptospira is harbored by Periplaneta spp. in Cali (Colombia) and the variables influencing this relationship. Fifty-nine cockroaches were captured from seven sites and DNA was extracted from the body surface and digestive tract for a multiplex polymerase chain reaction, targeting genes secY and flaB. Logistic regression models and proportion tests showed a higher likelihood for Leptospira to be isolated from body surfaces (P > 0.001) and from individuals inside houses (six times more likely). These findings are the first to demonstrate an association between Periplaneta spp. and Leptospira, suggesting the need to investigate the potential for cockroaches to serve as reservoirs or transport hosts for Leptospira. PMID- 26553296 TI - Indian endocrinologists set guidance to combat vitamin D deficiency. PMID- 26553294 TI - Metabolites involved in cellular communication among human cumulus-oocyte-complex and sperm during in vitro fertilization. AB - BACKGROUND: Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization. METHODS: For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated. RESULTS: The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC. CONCLUSIONS: LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction. PMID- 26553297 TI - C-H Photooxygenation of Alkyl Benzenes Catalyzed by Riboflavin Tetraacetate and a Non-Heme Iron Catalyst. AB - A mixture of the photocatalyst riboflavin tetraacetate (RFT) and the biomimetic non-heme iron complex [Fe(TPA)(MeCN)2](ClO4)2 (TPA = tris(2-pyridylmethyl)amine) efficiently catalyzes the visible-light-driven aerobic oxidation of alkyl benzenes to ketones and carboxylic acids. An RFT-catalyzed photocycle and the independent action of the iron complex as a catalyst for H2O2 disproportionation and alkyl benzene oxygenation ensure high yields and selectivities. PMID- 26553298 TI - A comprehensive analysis of the chorion locus in silkmoth. AB - Despite more than 40 years of intense study, essential features of the silkmoth chorion (eggshell) are still not fully understood. To determine the precise structure of the chorion locus, we performed extensive EST analysis, constructed a bacterial artificial chromosome (BAC) contig, and obtained a continuous genomic sequence of 871,711 base pairs. We annotated 127 chorion genes in two segments interrupted by a 164 kb region with 5 non-chorion genes, orthologs of which were on chorion bearing scaffolds in 4 ditrysian families. Detailed transcriptome analysis revealed expression throughout choriogenesis of most chorion genes originally categorized as "middle", and evidence for diverse regulatory mechanisms including cis-elements, alternative splicing and promoter utilization, and antisense RNA. Phylogenetic analysis revealed multigene family associations and faster evolution of early chorion genes and transcriptionally active pseudogenes. Proteomics analysis identified 99 chorion proteins in the eggshell and micropyle localization of 1 early and 6 Hc chorion proteins. PMID- 26553299 TI - CD45+ and CD45- lymphocyte populations identified by flow cytometry from dogs with lymphoma exhibit similar morphology and the same clonal (B cell or T cell) lineage. AB - Flow cytometric analysis of canine lymphoma sometimes demonstrates a mixed population of CD45+ and CD45- lymphocytes. Recently, indolent forms of canine lymphoma have been described which are associated with the loss of CD45 expression, warranting further investigation of the role of CD45 in canine lymphoma. The purpose of this study was to compare morphology and assess clonal origin between CD45+ and CD45- lymphocyte populations identified by flow cytometry in confirmed cases of canine B- and T-cell lymphoma. Our hypothesis was that the CD45- population of lymphocytes represented a phenotypic variant of the CD45+ population. Fifteen client-owned dogs with lymphoma and distinct CD45+ and CD45- lymphocyte populations identified by flow cytometry were identified for a blinded, prospective assessment of morphology and clonal origin (B cell or T cell) between populations of sorted CD45+ and CD45- cells. Lymphocytes were isolated from 11 dogs for paired cytologic evaluation. In 10/11 dogs, the CD45+ and CD45- samples were similar (95% C.I., 0.301-1.00). DNA was harvested from sorted populations of CD45+ and CD45- cells from 12/15 dogs and PARR analysis produced amplicons of identical size from both populations, indicating that 100% (12/12) were of the same lineage, B cell or T cell (95% C.I., 0.757-1.00). Collectively, our data suggests that the CD45- population identified in dogs with lymphoma represents a phenotypic variant of the CD45+ population. PMID- 26553300 TI - Development of an in vitro model of the early-stage bovine tuberculous granuloma using Mycobacterium bovis-BCG. AB - Mycobacterium bovis causes 3.1% of human tuberculosis cases, as described by the World Health Organisation. In cattle, this organism causes bovine tuberculosis (BTB) which can have a prevalence of up to 39.5% in some developing countries. In developed countries, although the prevalence of BTB has been reduced through eradication programmes, complete eradication has in some cases proved elusive, with prevalences in cattle of 0.5% in the Republic of Ireland and of 4.3% in the UK. As the tuberculous granuloma is the fundamental lesion that reflects the pathogenesis, immune control and progression of BTB, we aimed to develop an in vitro model of the early-stage bovine tuberculous granuloma, in order to model the early stages of BTB, while also reducing the use of experimentally infected animals. In vitro models of human and ovine mycobacterial granulomas have previously been developed; however, so far, there is no model for the BTB granuloma. As the disease in cattle differs in a number of ways from that in other species, we consider this to be a significant gap in the tools available to study the pathogenesis of BTB. By combining bovine monocyte-derived macrophages infected with M. bovis-BCG and autologous lymphocytes we have developed an early stage tuberculous bovine granuloma model. In the model, 3D cell aggregations formed a spherical-shape that grew for up to 11 days post-infection. This bovine tuberculous granuloma model can aid in the study of such lesion development, and in comparative studies of pathogenesis, such as, for example, the question of mycobacterial latency in bovine tuberculosis. PMID- 26553301 TI - Variations of the posterior cerebral artery diagnosed by MR angiography at 3 tesla. AB - INTRODUCTION: Fenestration, early bifurcation, and duplication of the posterior cerebral artery (PCA) and the so-called hyperplastic anterior choroidal artery (AChA), considered a variation of the PCA, are rare. We evaluated the prevalence and characteristic features of these PCA variations on magnetic resonance (MR) angiography. METHODS: We reviewed intracranial MR angiographic images of 2402 patients examined using a 3-tesla scanner. Images from the skull base to the intracranial region were obtained using the standard time-of-flight technique. We excluded images of 52 patients with insufficient image quality or occlusion of the PCA(s) and retrospectively evaluated the images of 2350 patients using a picture archiving and communication system. RESULTS: We observed PCA fenestration in eight (0.34%) patients, most at the P1 segment and P1-P2 junction and all small in size, early bifurcation at the P1-P2 junction or proximal P2A segment in eight (0.34%) patients, complete duplication in one patient, and hyperplastic AChA in 13 (0.55%) patients. Eleven of the 13 hyperplastic AChAs supplied only the territory of the temporal branch of the PCA, and the remaining two supplied the entire territory of the PCA. CONCLUSION: We observed PCA variations in 30 (1.28%) patients. We believe the name "hyperplastic AChA" inaccurately describes variations of the PCA in which the AChA supplies part of or all of the territory of the PCA and propose "accessory PCA" to describe an AChA that supplies part of the territory of the PCA or "replaced PCA" to describe that vessel that supplies the territory all branches of the PCA. PMID- 26553303 TI - Big data and ergonomics methods: A new paradigm for tackling strategic transport safety risks. AB - Big data collected from On-Train Data Recorders (OTDR) has the potential to address the most important strategic risks currently faced by rail operators and authorities worldwide. These risk issues are increasingly orientated around human performance and have proven resistant to existing approaches. This paper presents a number of proof of concept demonstrations to show that long standing ergonomics methods can be driven from big data, and succeed in providing insight into human performance in a novel way. Over 300 ergonomics methods were reviewed and a smaller sub-set selected for proof-of-concept development using real on-train recorder data. From this are derived nine candidate Human Factors Leading Indicators which map on to all of the psychological precursors of the identified risks. This approach has the potential to make use of a significantly underused source of data, and enable rail industry stakeholders to intervene sooner to address human performance issues that, via the methods presented in this paper, are clearly manifest in on-train data recordings. The intersection of psychological knowledge, ergonomics methods and big data creates an important new framework for driving new insights. PMID- 26553302 TI - Delayed hemorrhagic complications after flow diversion for intracranial aneurysms: a literature overview. AB - INTRODUCTION: Delayed aneurysm rupture and delayed intraparenchymal hemorrhages (DIPH) are poorly understood and often fatal complications of flow diversion (FD) for intracranial aneurysms. The purpose of this study was to identify risk factors for these complications. METHODS: We performed a systematic review on post-FD delayed aneurysm rupture and DIPH. For each reported case, we collected the following information: aneurysm location, size and rupture status, type of flow diverter used, timing of the hemorrhage, and neurological outcome. We reported descriptive statistics of patients suffering DIPH and delayed aneurysm rupture to determine if there were any characteristics consistently present among patients with these complications. RESULTS: We identified 81 delayed aneurysm ruptures and 101 DIPH. Of the delayed ruptures, 76.6% (45/58) occurred within 1 month. The prognosis of delayed ruptures was poor, with 81.3% (61/75) experiencing death or poor neurological outcome. Giant aneurysms accounted for 46.3% of ruptures (31/67). Of these aneurysms, 80.9% (55/68) were initially unruptured. Of the delayed ruptured aneurysms, 17.8% (13/73) had prior or concomitant coiling. DIPHs were ipsilateral to the treated aneurysm in 82.2% (60/73) of cases. Of the DIPH, 86.0% (43/50) occurred within 1 month after FDS. Combined morbidity/mortality rate was 68.5% (50/73) following DIPH. Of DIPHs, 23.0% (14/61) occurred in patients with giant aneurysms. CONCLUSIONS: Our study demonstrates that giant aneurysms represent almost 50% of delayed aneurysm ruptures in the flow diverter literature. About 2% of delayed ruptures occurred despite associated coiling. A substantial proportion of DIPHs occur early following FDS treatment of giant aneurysms. PMID- 26553304 TI - Informed consent instead of assent is appropriate in children from the age of twelve: Policy implications of new findings on children's competence to consent to clinical research. AB - BACKGROUND: For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives. DISCUSSION: Although assessment of children's competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad. Previous research outcomes showed that children's medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case by-case assessment of children's competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated. PMID- 26553305 TI - The Association Between Potentially Inappropriate Prescribing and Medication Related Hospital Admissions in Older Patients: A Nested Case Control Study. AB - INTRODUCTION: Medication-related problems can cause serious adverse drug events (ADEs) that may lead to hospitalization of the patient. There are multiple screening methods to detect and reduce potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). Whether this will result in less medication-related hospitalizations is unknown. The study objective was to assess the risk of preventable medication-related hospital admissions associated with potentially inappropriate prescribing, using the Beers 2012 and the Screening Tool of Older Person's Prescriptions and the Screening Tool to Alert doctors to Right Treatment (STOPP & START) 2008 criteria. DESIGN, SETTING AND PARTICIPANTS: A nested case-control study was conducted with a subset of Dutch participants from the Hospital Admissions Related to Medication (HARM) study. Cases were defined as patients aged >=65 years with a potentially preventable medication-related hospital admission. For each case, one control was selected, matched for age and sex. The primary determinant was the presence of one or more PIMs according to the Beers 2012 and STOPP 2008 criteria. The secondary determinant was the presence of one or more PIMs and PPOs according to the STOPP & START 2008 criteria. The strength of the association between inappropriate prescribing and medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: The prevalence of Beers 2012 criteria PIMs in the total cohort was 44.4 %. The prevalence of STOPP & START 2008 criteria PIMs and PPOs were, respectively, 34.1 and 57.7 %. STOPP 2008 criteria PIMs were associated with preventable medication-related hospital admissions [OR adjusted for number of drugs and comorbidities (ORadj) 2.30, 95 % CI 1.30-4.07], whereas there was no association with Beers 2012 criteria PIMs (ORadj 1.49, 95 % CI 0.90 2.47). STOPP PIMs and START PPOs together were also associated with preventable medication-related hospital admissions (ORadj 3.47, 95 % CI 1.70-7.09). CONCLUSION: Our study shows that patients with potentially inappropriate prescribing detected with the STOPP & START 2008 criteria are at risk of preventable medication-related hospital admissions. The STOPP & START 2008 criteria can be used to identify older people at risk of medication-related problems. PMID- 26553307 TI - A comparison of recreational drug use amongst sexual health clinic users in London with existing prevalence data. AB - The objective was to give an overview of self-reported recreational drug use amongst attendees of sexual health clinics in London and compare this to existing datasets. Between December 2013 and March 2014, attendees of two sexual health clinics in London were surveyed. Data collected were: sexual history, smoking and alcohol and recreational drug use. Data were analysed using SPSS (version 21). A total of 1472 respondents were included; 778 (52.9%) men, 676 (45.9%) women and 3 (0.2%) transgender (15 [1.0%] did not answer). Mean age was 30.6 +/- 9.0 years. A total of 339 (43.6%) men were men who have sex with men (MSM), and 18 (2.4%) women were women who have sex with women. Lifetime prevalence of use was: alcohol 94.1%; cannabis 48.5%; 'poppers' (volatile nitrites) 28.2%; cocaine 26.8% and 3,4 methylenedioxy-methamphetamine pills 23.2%. Our population had higher current popper, methamphetamine and mephedrone use than the Crime Survey of England and Wales but lower use of cannabis, poppers and Viagra than the European MSM Internet Survey. Global Drug Survey and Part of the Picture respondents' use were higher than our population for all drugs. Drug use in this population had a different pattern to general population surveys and studies involving only MSM. PMID- 26553306 TI - First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies. AB - PURPOSE: Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. METHODS: This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). RESULTS: In the dose escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. CONCLUSIONS: In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC. PMID- 26553308 TI - The breakdown of superlubricity by driving-induced commensurate dislocations. AB - In the framework of a Frenkel-Kontorova-like model, we address the robustness of the superlubricity phenomenon in an edge-driven system at large scales, highlighting the dynamical mechanisms leading to its failure due to the slider elasticity. The results of the numerical simulations perfectly match the length critical size derived from a parameter-free analytical model. By considering different driving and commensurability interface configurations, we explore the distinctive nature of the transition from superlubric to high-friction sliding states which occurs above the critical size, discovering the occurrence of previously undetected multiple dissipative jumps in the friction force as a function of the slider length. These driving-induced commensurate dislocations in the slider are then characterized in relation to their spatial localization and width, depending on the system parameters. Setting the ground to scale superlubricity up, this investigation provides a novel perspective on friction and nanomanipulation experiments and can serve as a theoretical basis for designing high-tech devices with specific superlow frictional features. PMID- 26553310 TI - Pediatric Auditory Brainstem Implant Surgery. AB - Auditory brainstem implants (ABIs) provide auditory perception in patients with profound hearing loss who are not candidates for the cochlear implant (CI) because of anatomic constraints or failed CI surgery. Herein, the authors discuss (1) preoperative evaluation of pediatric ABI candidates, (2) surgical approaches, and (3) contemporary ABI devices and their use in the pediatric population. The authors also review the surgical and audiologic outcomes following pediatric ABI surgery. The authors' institutional experience and the nearly 200 cases performed in Europe and the United States indicate that ABI surgery in children can be safe and effective. PMID- 26553309 TI - Construction of a high-density linkage map and fine mapping of QTL for growth in Asian seabass. AB - A high-density genetic map is essential for comparative genomic studies and fine mapping of QTL, and can also facilitate genome sequence assembly. Here, a high density genetic map of Asian seabass was constructed with 3321 SNPs generated by sequencing 144 individuals in a F2 family. The length of the map was 1577.67 cM with an average marker interval of 0.52 cM. A high level of genomic synteny among Asian seabass, European seabass, Nile tilapia and stickleback was detected. Using this map, one genome-wide significant and five suggestive QTL for growth traits were detected in six linkage groups (i.e. LG4, LG5, LG11, LG13, LG14 and LG15). These QTL explained 10.5-16.0% of phenotypic variance. A candidate gene, ACOX1 within the significant QTL on LG5 was identified. The gene was differentially expressed between fast- and slow-growing Asian seabass. The high-density SNP based map provides an important tool for fine mapping QTL in molecular breeding and comparative genome analysis. PMID- 26553311 TI - Blaschkolinear lichen nitidus. PMID- 26553312 TI - A 'turn-on' fluorescent chemosensor for quantification of serum albumin in aqueous solution at neutral pH. AB - A fluorescent chemosensor 1 (4-diethylamino-2'-hydroxychalcone) for detecting serum albumin with long-wavelength emission, good selectivity and facile synthesis was reported. Upon the addition of bovine serum albumin (BSA) to an aqueous solution of 1 at neutral pH, a 'turn-on' fluorescence response was observed at 596 nm based on a hydrophobic binding mode between 1 and BSA. A linear range of 0.10-1.00 mg/mL and a detection limit of 9.1 ug/mL for BSA were obtained, respectively. Moreover, 1 was successfully applied to detect BSA in real bovine serum samples with satisfied recovery and accuracy, which suggested that 1 could serve as a valid and effective fluorescent chemosensor for quantification of BSA. PMID- 26553314 TI - Metal-free Bronsted acid mediated synthesis of fully substituted thiophenes via chemo- and regioselective intramolecular cyclization of alpha,alpha'-bis(beta oxodithioesters) at room temperature. AB - Metal-free para-toluenesulfonic acid mediated straightforward synthesis of hitherto unreported tetrasubstituted thiophenes has been achieved in quantitative yields by chemo- and regioselective dehydrative cyclization of alpha,alpha' bis(beta-oxodithioesters) at room temperature. Notably, the dithioester group at the 4-position of the thiophene ring has been further transformed to a thiazoline group. PMID- 26553313 TI - Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease. AB - OBJECTIVES: A series of preclinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects. The present study primarily aimed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer's disease (AD). We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants. METHODS: Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and randomly assigned in a 1:1 ratio. Each group received 20 mg/day of escitalopram or placebo for 52 weeks. The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks. The Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia (CSDD) were also applied. RESULTS: We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups. Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo (t = -2.17, df = 50.42, p = 0.035), but this finding did not persist throughout the study. CONCLUSION: The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD. However, the negative results of the present trial should be interpreted cautiously because of the relatively small sample size. Further large scale escitalopram trials targeting the earlier stages of AD, even prodromal AD, are still needed. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553315 TI - Morphology, mechanical and thermal oxidative aging properties of HDPE composites reinforced by nonmetals recycled from waste printed circuit boards. AB - In this study nonmetals recycled from waste printed circuit boards (NPCB) is used as reinforce fillers in high-density polyethylene (HDPE) composites. The morphology, mechanical and thermal oxidative aging properties of NPCB reinforced HDPE composites are assessed and it compared with two other commercial functional filler for the first time. Mechanical test results showed that NPCB could be used as reinforcing fillers in the HDPE composites and mechanical properties especially for stiffness is better than other two commercial fillers. The improved mechanical property was confirmed by the higher aspect ratio and strong interfacial adhesion in scanning electron microscopy (SEM) studies. The heat deflection temperature (HDT) test showed the presence of fiberglass in NPCB can improve the heat resistance of composite for their potential applications. Meanwhile, the oxidation induction time (OIT) and the Fourier transform infrared (FTIR) spectroscopy results showed that NPCB has a near resistance to oxidation as two other commercial fillers used in this paper. The above results show the reuse of NPCB in the HDPE composites represents a promising way for resolving both the environmental pollution and the high-value reuse of resources. PMID- 26553316 TI - An innovative approach to recover the metal values from spent lithium-ion batteries. AB - A new approach to recover metal values from spent lithium-ion batteries with a simple and environmentally friendly method is investigated. Two stages of water washing of the mixed black powder resulted in satisfactory separation of cobalt and lithium. Lithium in the wash liquor is precipitated using saturated sodium carbonate solution. Cobalt oxide in the residue is purified by removing organic matrix through roasting followed by dilute acid washing. The purities of the products obtained during the processes are analyzed by Microwave Plasma-Atomic Emission Spectrophotometer and confirmed from X-ray diffraction analysis. The overall process is safe, economic and can be scaled up for commercial production. Based on the process steps involved, a flow sheet is proposed for industrial application. PMID- 26553317 TI - Characterization of the biological processes shaping the genetic structure of the Italian population. AB - BACKGROUND: The genetic structure of human populations is the outcome of the combined action of different processes such as demographic dynamics and natural selection. Several efforts toward the characterization of population genetic architectures and the identification of adaptation signatures were recently made. In this study, we provide a genome-wide depiction of the Italian population structure and the analysis of the major determinants of the current existing genetic variation. RESULTS: We defined and characterized 210 genomic loci associated with the first Principal Component calculated on the Italian genotypic data and correlated to the North-south genetic gradient. Using a gene-enrichment approach we identified the immune function as primarily involved in the Italian population differentiation and we described a locus on chromosome 13 showing combined evidence of North-south diversification in allele frequencies and signs of recent positive selection. In this region our bioinformatics analysis pinpointed an uncharacterized long intergenic non-coding (lincRNA), whose expression appeared specific for immune-related tissues suggesting its relevance for the immune function. CONCLUSIONS: Our study, combining population genetic analyses with biological insights provides a description of the Italian genetic structure that in future could contribute to the evaluation of complex diseases risk in the population context. PMID- 26553318 TI - PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization. AB - Prefoldin (PFDN) subunits have been reported upregulated in various tumor types, while the expression and functions of PFDN1 (PFDN subunit 1) in colorectal cancer (CRC) are not well elucidated. The aim of this study was to investigate the use of PFDN1 as a poor prognosis indicator for CRC and explore the functions of PFDN1 in CRC. The relationship between PFDN1 expression and CRC clinical-pathological statistics was detected on the tissue microarray containing 145 cases of CRC. ShRNA was used to silence PFDN1 expression in SW480 and RKO CRC cells, and these transfected cells were analyzed for changes in proliferation, colony formation, cell cycle, migration, and invasion. Immunofluorescence and immunoblot were used to determine the remodeling of the F-actin and alpha-tubulin. Finally, tumor growth on nude mice was observed and measured. In this study, we found PFDN1 was upregulated in CRC tissues compared with adjacent normal tissues. Also, PFDN1 expression positively correlated with tumor size and tumor invasion. Moreover, after silencing PFDN1 in SW480 and RKO cells, the proliferation and motility of CRC cells were significantly suppressed. The inhibitory effect of PFDN1 on tumor cell growth and motility was partially due to G2/M cell cycle blockage and cytoskeletal deficiency. Finally, in vivo assay showed that downregulation of PFDN1 inhibited tumor growth on nude mice and PFDN1 expression correlated with higher levels of Ki-67 staining. These findings indicate that PFDN1 was involved in the progression of CRC, and provide new insights into PFDN1 as a potential therapeutic target for CRC treatment. PMID- 26553319 TI - Metallic copper spray--a new control technique to combat invasive container inhabiting mosquitoes. AB - BACKGROUND: The control of container-inhabiting mosquitoes is mainly based on environmental management with special emphasis on community participation e.g. source reduction by elimination or modification of water bodies. However, citizens are often not aware of the problems related to urban mosquito control or just ignore the advice provided during anti-mosquito control campaigns. In particular, cemeteries contain favourite breeding sites for container-inhabiting mosquitoes like Ochlerotatus j. japonicus, Culex pipiens s.l./Cx. torrentium, Aedes aegypti or Aedes albopictus. In our study, we investigated whether metallic copper e.g. in form of copper spray can be a suitable and cost-effective tool to combat mosquito breeding in vases or other similar small containers where no commonly used insecticides can be applied. METHODS: The effect of metallic copper spray in comparison to 5 Euro cent coins or copper tubes at different dosages and water qualities applied in small water collections such as widely used plastic grave vases were evaluated by assessing the mortality rates of larvae of Oc.j. japonicus, Cx. pipiens s.l./Cx. torrentium and Ae.aegypti. Different water qualities were tested to assess the influence of pH on the solubility of the copper ions. The copper concentrations were quantified using ICP/MS (Inductively coupled plasma/Mass spectrometry) in relation to the exposure time and mortality rates of mosquito larvae. All statistical analyses were computed using JMP 10.0.2 (SAS Institute Inc., 2012, Cary, NC, USA). RESULTS: Dosages of less than 500 ppb of copper in the water of small containers led to a 100% mortality rate after 2 weeks for all tested mosquito species by using one or more 5 Euro cent coins/vase. When the interior surface of plastic grave vases was covered by metallic copper spray, all of the tested larvae died after 7-10 days in the laboratory and under field conditions the reduction rate was 99.44% for Oc.j. japonicus and 99.6% for Culex pipiens s.l./Cx. torrentium larvae for a period of about 3 months. CONCLUSION: The use of metallic copper spray provides a sustainable control of container-inhabiting mosquitoes at low costs. The amount of dissolved copper in water (about 500 ppb) is far below the critical value for drinking water according to the WHO recommendations and is therefore not detrimental for the environment. PMID- 26553320 TI - Impact of nicotine on the interplay between human periodontal ligament cells and CD4+ T cells. AB - Periodontitis is a common infectious disease associated with destruction of periodontal ligaments and alveolar bones. CD4(+) T cell-mediated immune response is involved in the progression of periodontitis. Tobacco consumption increases the risk of periodontal disease. However, the impact of nicotine on the interaction between human periodontal ligament (PDL) cells and CD4(+) T cells remains unrevealed. Our study aims to investigate the effect of nicotine on PDL cells and the cocultured CD4(+) T cells. The PDL cell cultures were established by explants from healthy individuals, exposed to nicotine or alpha-bungarotoxin (alpha-BTX), and incubated solely or in combination with CD4(+) T cells. Afterwards, cell viability, secreted cytokines, and matrix metalloproteinases (MMPs) were evaluated. In monoculture of PDL cells, nicotine dramatically repressed cell viability and increased apoptosis. Meanwhile, alpha-BTX largely reversed the nicotine-induced apoptosis and increased viability of PDL cells. Compared with the monoculture, MMP-1, MMP-3, interleukin (IL)-1beta, IL-6, IL-17, and IL-21 in supernatant of cocultures were markedly elevated after treatment with nicotine. Moreover, alpha-BTX significantly attenuated nicotine-triggered production of these components either in mono- or co-cultures. In addition, PDL cell-derived CXCL12 following nicotine treatment recruited CD4(+) T cells. Above all, nicotine deteriorated periodontitis partially by promoting PDL cell-CD4(+) T cell-mediated inflammatory response and matrix degradation. PMID- 26553321 TI - Human and experimental toxicology of orellanine. AB - Orellanine is a nephrotoxic toxin produced by some mushroom species of the Cortinarius genus, typically found in Europe and North America. The nephrotoxicity of Cortinarius orellanus is well known and was first recognized in the 1950s when this mushroom was identified as the cause of a mass poisoning in Poland. Typically, onset of symptoms is delayed for 1-2 weeks after ingestion. Some patients suffer mild gastrointestinal discomfort in the latency period before developing signs of renal impairment due to severe interstitial nephritis, acute focal tubular damage, and interstitial fibrosis. There is no specific antidote to orellanine poisoning. The mainstay of treatment is the prevention of secondary complications of kidney failure, adequate dialysis and, in the case of incomplete recovery, management of chronic renal insufficiency. : In this work, we aim to review about Cortinarius species, including epidemiological studies, chemical structure, toxicokinetics, toxic doses, mechanisms of toxicity, diagnosis, prognosis, and treatment options. PMID- 26553322 TI - Detection of paternally inherited fetal point mutations for beta-thalassemia in maternal plasma using simple fetal DNA enrichment protocol with or without whole genome amplification: an accuracy assessment. AB - OBJECTIVE: To design and evaluate a noninvasive protocol for prenatal diagnosis (PND) of beta-thalassemia, using cell free fetal DNA (cff-DNA) in maternal circulation. Traditional current PND which is mainly based on chorionic villous sampling (CVS), amplification refractory mutation system and sequencing holds as gold standard. METHODS: Ten thalassemia trait couples with distinct mutations for the husband and wife were included in this study. The mutations in carrier fathers were IVSI-1, IVSI-5, FR8/9 and CD44. After maternal plasma isolation and free DNA extraction, all samples subjected to designed protocol including DNA size separation on agarose gel, elution of DNA from the gel slices using a simple and efficient manual purification method, with or without whole genome amplification and the detection method was allele-specific real-time PCR. RESULTS: Presence or absence of the paternal mutant allele was correctly determined in all of cases and the accuracy of designed protocol was determined 100%. CONCLUSIONS: The protocol described here is very simple, inexpensive and easy to perform, but with satisfactory accuracy in detection of paternal mutations in cff-DNA. Due to the risk of fetal loss with current invasive sampling for PND, a noninvasive alternative is highly demanded in clinical setting. PMID- 26553324 TI - That was the year that was. PMID- 26553325 TI - The influence of ALA-mediated photodynamic therapy on secretion of selected growth factors by colon cancer cells in hypoxia-like environment in vitro. AB - BACKGROUND: Photodynamic therapy (PDT) affects the immune system and tumor cells' secretory activity. Hypoxia may limit PDT effects. The aim of this study was to determine the influence of PDT with aminolevulinic acid (ALA-PDT) in a hypoxic like microenvironment on the secretion of growth factors: GM-CSF (granulocyte and macrophage colony stimulating factor), G-CSF (granulocyte colony-stimulating factor) and FGF (fibroblast growth factor) by experimental models of colon cancer cells in vitro. METHODS: Sublethal doses of ALA-PDT (ALA of 1000 MUM, light fluence 10J/cm(2), power density rate of 1.5mW/cm(2), wavelength 600-720nm) were administered to two colorectal cancer cell lines varying in malignancy potential: SW480 (local malice) and SW620 (high metastatic activity) under normoxia and hypoxia-like environment. Hypoxia-mimic conditions were achieved by adding environment cobalt (II) chloride. Concentrations of growth factors were analyzed with Bio-Plex ProTM Assay. RESULTS: ALA-PDT amplified the secretion of GM-CSF by both cell lines. The decrease in secretion of G-CSF and FGF was noticed in the SW620. SW620 line cells secreted higher levels of FGF and G-CSF, while SW480 cells more actively released GM-CSF. Compared to normoxic condition, no differences in the secretion of these factors in a hypoxic-like environment were found. CONCLUSIONS: ALA-PDT increased GM-CSF secretion, which stimulates antitumor defense and decreased secretion of FGF and G-CSF-factors responsible for tumor progression. No differences in the effects of ALA-PDT in the hypoxic like environment suggests that the beneficial results of PDT are also continued in the later stages of the reaction. PMID- 26553323 TI - Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease. AB - One of the primary deficits in Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra pars compacta which leads to striatal dopaminergic deficits that underlie the motor symptoms associated with the disease. A plethora of animal models have been developed over the years to uncover the molecular alterations that lead to PD development. These models have provided valuable information on neurotransmitter pathways and mechanisms involved. One such a system is the nicotinic cholinergic system. Numerous studies show that nigrostriatal damage affects nicotinic receptor-mediated dopaminergic signaling; therefore therapeutic modulation of the nicotinic cholinergic system may offer a novel approach to manage PD. In fact, there is evidence showing that nicotinic receptor drugs may be useful as neuroprotective agents to prevent Parkinson's disease progression. Additional preclinical studies also show that nicotinic receptor drugs may be beneficial for the treatment of L-dopa induced dyskinesias. Here, we review preclinical findings supporting the idea that nicotinic receptors are valuable therapeutic targets for PD. PMID- 26553326 TI - Perceptions of Cancer Risk: Differences by Weight Status. AB - Despite the strong link between obesity and cancer development, individuals are less likely to identify obesity as a risk factor for cancer than family history. Family history of cancer has been documented to influence perceived risk of developing cancer, yet it is unclear if excess weight impacts cancer risk perceptions. The purpose of this study was to examine absolute and relative risk perceptions for cancer by weight status. Cross-sectional data were obtained from the National Cancer Institute's 2011 Health Information National Trends Survey (n = 2585). Demographics, anthropometric data, family history of cancer, health behaviors, and absolute and relative cancer risk perceptions were evaluated. The effect of weight and family history on absolute and relative cancer risk perceptions was analyzed through weighted descriptive and logistic regression analyses. 22.8 and 28.6 % of subjects reported that they were very unlikely/unlikely to develop cancer in their lifetime (absolute risk) and when compared to others their age (relative risk), respectively. Findings indicated differences in risk perceptions between those with and without a family history of cancer (p < 0.0001). No significant differences were found between BMI categories for absolute cancer risk perceptions despite stratification by family history. Obese subjects were more likely to have an increased relative risk perception of cancer compared to healthy weight subjects (p = 0.0066); this association remained significant when stratified by family history (p = 0.0161). Educating individuals, especially those who are overweight/obese, about the impact of excess weight on cancer risk may improve risk accuracy and promote cancer risk reduction through weight management. PMID- 26553327 TI - Cancer Patients and the Internet: a Survey Among German Cancer Patients. AB - An increasing number of patients and relatives use the Internet to get additional or initial information about their disease. The aim of the study was to reevaluate the Internet usage among German cancer patients. Using a standardized questionnaire, we did an anonymous survey on patients attending a series of lectures on complementary medicine in 2014. We received 255 questionnaires. Nearly 80 % of the participants stated that they used the Internet to read up information about health or medicine issues. There was no significant difference regarding gender, age, or status (patient, current treatment/former treatment; relatives). Most users use the Internet in order to get additional information after a consultation with a physician (82.2 %). Important qualities from the view of the patient are a trustable source (65.3 %), information from experts (59.6 %), and actual information (52.8 %). There is an increasing number of patients in Germany looking for information in the Internet mostly in the intention of getting additional information. Yet, as the quality of information is heterogeneous, false information may lead to distrust in the doctor or wrong decision-making. Accordingly, organizations working on improving quality of cancer care should engage in conveying comprehensive and actual information adapted to the needs of patients. Physicians should know trustful websites for referral of patients. PMID- 26553328 TI - Cancer genetics: RNA-seq for blood-based pan-cancer diagnostics. PMID- 26553329 TI - Methods and models for unravelling human evolutionary history. AB - The genomes of contemporary humans contain considerable information about the history of our species. Although the general contours of human evolutionary history have been defined with increasing resolution throughout the past several decades, the continuing deluge of massively large sequencing data sets presents new opportunities and challenges for understanding human evolutionary history. Here, we review the signatures that demographic history imparts on patterns of DNA sequence variation, statistical methods that have been developed to leverage information contained in genome-scale data sets and insights gleaned from these studies. We also discuss the importance of using exploratory analyses to assess data quality, the strengths and limitations of commonly used population genomics methods, and factors that confound population genomics inferences. PMID- 26553331 TI - Defining the Incremental Utility of Prostate Multiparametric Magnetic Resonance Imaging at Standard and Specialized Read in Predicting Extracapsular Extension of Prostate Cancer. AB - Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in staging early prostate cancer (PCa) but remains heavily reader-dependent. We aim to define the incremental utility of mpMRI over clinical parameters in determining the pathologic extracapsular extension (pECE) of PCa interpreted in a standard radiologic setting and when further over-read by a specialized reader. We retrospectively reviewed 120 men with clinically localized PCa undergoing mpMRI and radical prostatectomy. We obtained radiologic prediction of pECE from standard radiologic reports (standard read) and by a specialized reader blinded to clinical and pathologic findings (specialized read). We determined the incremental benefit of standard read and specialized read by sequential addition to a baseline clinical parameters-only logistic regression model predicting pECE. The sensitivity and specificity of standard read were 77% and 44%, respectively, whereas those of specialized read were 86% and 81%. The positive likelihood ratio was 1.7 at baseline, 1.7 adding standard read, and 6.5 adding specialized read. The negative likelihood ratio was 0.6 at baseline, 0.5 adding standard read, and 0.1 adding specialized read. Standard read modestly improved prediction of pECE, whereas specialized read improved it moderately. PATIENT SUMMARY: The incremental benefit of mpMRI over clinical information is small but increases to moderate with a specialized second opinion. This second opinion may be useful when considering active surveillance, nerve-sparing surgery, or focal therapy. PMID- 26553330 TI - Human genotype-phenotype databases: aims, challenges and opportunities. AB - Genotype-phenotype databases provide information about genetic variation, its consequences and its mechanisms of action for research and health care purposes. Existing databases vary greatly in type, areas of focus and modes of operation. Despite ever larger and more intricate datasets--made possible by advances in DNA sequencing, omics methods and phenotyping technologies--steady progress is being made towards integrating these databases rather than using them as separate entities. The consequential shift in focus from single-gene variants towards large gene panels, exomes, whole genomes and myriad observable characteristics creates new challenges and opportunities in database design, interpretation of variant pathogenicity and modes of data representation and use. PMID- 26553332 TI - Impacts of gender, weather, and workplace differences in farm worker's gear. AB - BACKGROUND: The farmers cannot help working in outdoor conditions which have high humidity and solar radiation during the harvest period. Wearable items including clothing are the nearest environment of human body, and to understand the current state of them can be a way to set up an active prevention strategy against the health risk from heat stress in summertime agriculture. The aim of this study was to investigate the work wear and accessories which the elderly farmers used during agricultural working. METHODS: One hundred twenty farmers (49 males and 71 females) working in nine separate sites on different days took part in this study. The average age of subjects was 61 years old. We examined the types of working posture, clothing, and items that the farmers used and/or wore. We also interviewed the farmers to know why they used such items while working. RESULTS: The results of this study were as follows: (1) Farmers worked in the thermal environment which was over wet bulb globe temperature (WBGT) reference value, and the farmers could suffer heat stress due to workload induced from wearing conventional long-sleeved shirts and long trousers which were 0.66 clo in average under this summertime working thermal condition. (2) The farmers tended to change the layer of upper clothing for adapting to weather condition. (3) The types of footwear used seemed to be related with facilities as well as weather, and farmers tended to wear lighter footwear when the weather is hotter or when they work in PVC greenhouse. The majority of elderly farmers wore loafers and rubber shoes which had indistinguishable thin soles. (4) The types of hats showed the difference between facilities as well as gender and only 31.7% of all participants used long brims. (5) Korean elderly farmers did not use any active cooling item as agricultural auxiliary tools in summer harvesting time. CONCLUSIONS: Korean elderly farmers worked in poor surroundings which could threaten their health and safety and seemed not to adjust their workload and clothing during summer harvest season. Thus, it would be necessary to monitor individual responses in order to ensure that the risk of heat stress is prevented. PMID- 26553334 TI - Online food nutrition labelling in the UK: how consistent are supermarkets in their presentation of nutrition labels online? AB - OBJECTIVE: To evaluate consistency levels of nutrition labelling on supermarket websites. DESIGN: This is a comparative, quantitative study examining page position, content and design of nutrition labels on own-brand and branded products. Online and in-store nutrition labels were examined, categorised and analysed to discern variety of label designs used and consistency between online and in-store labelling. SETTING: Five large online food retailers in the UK. SUBJECTS: Nutrition labels displayed on 100 webpages were examined for twenty branded and own-brand products. Equivalent labels on in-store packaged products were also examined. RESULTS: Eight different combinations of nutrition label designs were found. The online supermarket sites were found to use from three to six of these label combinations across the sample. The consistency level between online and in-store package labels ranged from 25 % to 90 %. In many cases the nutrition label required scrolling to view and in all cases items could be purchased without the label being visible from the search result listings. CONCLUSIONS: The main recommendation of the paper is that online nutrition labelling needs to be much more consistently presented than is currently practised, both within each website and between online and in-store experiences. Particular attention should be made to polychrome colour and the inclusion of summary graphics. Designers should also ensure visibility of the label and raise its vertical page position. The paper also proposes additional expansion of the use of nutrition information online, using nutrition values as database fields in search criteria and checkout aggregation reporting. PMID- 26553333 TI - Serotypes of group B streptococci in western Sweden and comparison with serotypes in two previous studies starting from 1988. AB - BACKGROUND: Group B Streptococci (GBS) are the most common neonatal pathogens and infect immunocompromised and elderly individuals. The species has 10 different serotypes. Serotypes have been studied in the south-west area of Sweden in 1988 1997 and 1998-2001. The aim of this study was to study serotypes in the same area from 2004 to 2009. METHODS: Invasive GBS isolates were collected prospectively from 2004 to 2009 in two counties in western Sweden with a population of 1.8 million, and were serotyped by latex agglutination. Clinical data were obtained from hospital records. During the study period 410 invasive GBS isolates from 398 patients were collected (multiple episodes >= 1 month apart). Clinical data were not available for two patients who are excluded. Four isolates were from stillborn neonates, 88 were from live born neonates and infants, and 318 from adults. RESULTS: Serotype III was the most common serotype (48%) in neonates and infants followed by serotypes Ia (18%) and V (16%). In adults serotype V (39%) dominated followed by serotypes III (20%) and Ib (14%). There was a significant increase of serotype V in comparison with the first study (1988-1997) but there were no significant changes in the serotype distribution between the present study and the second study (1998-2001). There were a few cases of serotype VI-IX, both in children and adults, not seen in the previous studies. Serotype V was more common among patients with arthritis than with any other manifestation. CONCLUSIONS: Changes in GBS serotypes occur over time in the same region, which must be considered when GBS vaccines are formulated. PMID- 26553335 TI - More than just trash bins? Potential roles for extracellular vesicles in the vertical and horizontal transmission of yeast prions. AB - In the yeast Saccharomyces cerevisiae, an ensemble of structurally and functionally diverse cytoplasmic proteins has the ability to form self perpetuating protein aggregates (e.g. prions) which are the vectors of heritable non-Mendelian phenotypic traits. Whether harboring these prions is deleterious akin to mammalian degenerative disorders-or beneficial-as epigenetic modifiers of gene expression-for yeasts has been intensely debated and strong arguments were made in support of both views. We recently reported that the yeast prion protein Sup35p is exported via extracellular vesicles (EV), both in its soluble and aggregated infectious states. Herein, we discuss the possible implications of this observation and propose several hypotheses regarding the roles of EV in both vertical and horizontal propagation of 'good' and 'bad' yeast prions. PMID- 26553336 TI - Opioid Prescribing at Hospital Discharge Contributes to Chronic Opioid Use. AB - BACKGROUND: Chronic opioid therapy for chronic pain treatment has increased. Hospital physicians, including hospitalists and medical/surgical resident physicians, care for many hospitalized patients, yet little is known about opioid prescribing at hospital discharge and future chronic opioid use. OBJECTIVE: We aimed to characterize opioid prescribing at hospital discharge among 'opioid naive' patients. Opioid naive patients had not filled an opioid prescription at an affiliated pharmacy 1 year preceding their hospital discharge. We also set out to quantify the risk of chronic opioid use and opioid refills 1 year post discharge among opioid naive patients with and without opioid receipt at discharge. DESIGN: This was a retrospective cohort study. PARTICIPANTS: From 1 January 2011 to 31 December 2011, 6,689 opioid naive patients were discharged from a safety-net hospital. MAIN MEASURE: Chronic opioid use 1 year post discharge. KEY RESULTS: Twenty-five percent of opioid naive patients (n = 1,688) had opioid receipt within 72 hours of discharge. Patients with opioid receipt were more likely to have diagnoses including neoplasm (6.3% versus 3.5%, p < 0.001), acute pain (2.7% versus 1.0 %, p < 0.001), chronic pain at admission (12.1% versus 3.3%, p < 0.001) or surgery during their hospitalization (65.1% versus 18.4%, p < 0.001) compared to patients without opioid receipt. Patients with opioid receipt were less likely to have alcohol use disorders (15.7% versus 20.7%, p < 0.001) and mental health disorders (23.9% versus 31.4%, p < 0.001) compared to patients without opioid receipt. Chronic opioid use 1 year post discharge was more common among patients with opioid receipt (4.1% versus 1.3%, p < 0.0001) compared to patients without opioid receipt. Opioid receipt was associated with increased odds of chronic opioid use (AOR = 4.90, 95% CI 3.22 7.45) and greater subsequent opioid refills (AOR = 2.67, 95% CI 2.29-3.13) 1 year post discharge compared to no opioid receipt. CONCLUSION: Opioid receipt at hospital discharge among opioid naive patients increased future chronic opioid use. Physicians should inform patients of this risk prior to prescribing opioids at discharge. PMID- 26553337 TI - Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients. AB - BACKGROUND: Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients. OBJECTIVE: We aimed to determine the net impact of PPIs on hospital mortality among medical inpatients. DESIGN: A microsimulation model, using literature derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality. PARTICIPANTS: Simulated general medical inpatients outside the intensive care unit (ICU). MAIN MEASURE: Change in overall mortality during hospitalization. KEY RESULTS: New initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios. CONCLUSIONS: For the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged. PMID- 26553338 TI - Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer. AB - BACKGROUND: Infertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro. METHODS: The study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs. RESULTS: Hematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule. CONCLUSIONS: The present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular tissue in young pre-pubertal boys for restoring spermatogenesis in adulthood is still in experimental stages. PMID- 26553341 TI - Erratum to: Pharmacologic Targeting of Regulatory T Cells for Solid Organ Transplantation: Current and Future Prospects. PMID- 26553339 TI - Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions. AB - Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor gamma (PPARgamma) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction. PMID- 26553340 TI - Exploring providers' perspectives of a community based TB approach in Southern Ethiopia: implication for community based approaches. AB - BACKGROUND: There is increasing interest in the role of close-to-community providers in supporting universal health coverage, but questions remain about the best approaches to supporting and motivating these providers, and the optimal package they can deliver indifferent contexts and support required. We report on the experiences of different health providers involved in a community based intervention to support access to tuberculosis diagnosis and treatment in Southern Ethiopia. METHODS: The aim of the study is to explore the experiences of health providers in delivering a community-based tuberculosis package in southern Ethiopia and to draw lessons for community-based programmes. A qualitative methodology was used. Methods included in-depth interviews (IDIs, n= 37) with all health provider groups: Community health promoters (CHPs), health extension workers (HEWs), district supervisors and laboratory technicians were undertaken to obtain a detailed understanding of the experiences of providers in the community based tuberculosis package. These were complemented with cadre specific focus group discussions (n= 3). We used the framework approach for qualitative analysis. RESULTS: The key theme that emerged was the positive impact the community-based intervention had on vulnerable groups' access to diagnosis, care and treatment for tuberculosis. Providers found the positive feedback from, and visible impact on, communities very motivating. Other themes related to motivation and performance included supervision and support; learning new skills; team problem solving/ addressing challenges and incentives. Against the backdrop of the Ethiopian Health Extension Programme (HEP), HEWs were successfully able to take on new tasks (collecting sputum and preparing smears) with additional training and appropriate support from supervisors, laboratory technicians and CHPs. CONCLUSION: All categories of providers were motivated by the high visible impact of the community-based intervention on poor and vulnerable communities and households. HEWs role in the community-based intervention was supported and facilitated through the structures and processes established within the community based intervention and the broader nation-wide Health Extension Programme. Within community based approaches there is need to develop context embedded strategies to support, sustain and motivate this critical cadre who play a pivotal role in linking health systems and rural communities. PMID- 26553342 TI - Detection and survey of coffee ringspot virus in Brazil. AB - Coffee ringspot virus (CoRSV) a member of the proposed genus "Dichorhavirus", was surveyed on commercial and research farms spanning an area responsible for the majority of Coffea arabica production in Brazil. Virus-infected plants were found at one hundred percent of locations (n = 45) sampled. All cultivars, regardless of cherry color, were found to serve as hosts, suggesting that there is limited resistance in commercially employed germplasm. Reverse transcription PCR analysis revealed that the virus is contained within symptomatic lesions, with little systemic spread throughout leaves. Phylogenetic analysis based on the ORF1 (nucleocapsid) gene identified a strong geo-spatial relationship among isolates, which clustered into three clades. Despite low genetic diversity among isolates, variation in symptom expression was observed in the experimental host Chenopodium quinoa. Our analyses support the hypothesis that the spread of CoRSV is constrained by the clonal expansion of thelytokous populations of Brevipalpus phoenicis. The widespread occurrence of this virus suggests that it is much more prevalent than previously thought. PMID- 26553344 TI - Travel as a Transformational Spiritual Event. AB - There is a philosophical connection between elements of travel and elements of spirituality. Nurses can develop spiritual intelligence, hone transcultural skills, and develop cultural humility through travel. Concepts of spiritual intelligence are incorporated to distinguish spirituality from religion. This discussion is to describe the spiritual attributes of travel through exploration of unique cultural sameness and differences, stepping out of one's routine, experiences of solitude, and the application to nursing. Venues such as study abroad, mission trips, cultural exchange opportunities, and service learning projects all can provide meaningful times of transformation, spiritual growth, learning new ways of doing things, and of being in the world. Nurses who integrate these practices into the care they provide daily will be enriched personally and rewarded with improved outcomes. PMID- 26553343 TI - Tracking practice effects in computation estimation. AB - The present study investigated college students' ability to estimate the results of multi-digit multiplication problems and the extent to which this ability improves with practice. Participants judged whether the results of multiplication problems composed of two-digit numbers were larger or smaller than a given reference number. The reference numbers were either close or far from the exact answer. The effects of practice, size, and distance of the reference number from the exact answer were examined using four measures of performance: speed, accuracy, eye movements, and strategy use. The results show that together with enhanced speed and accuracy with practice, participants also changed the pattern of eye movements and the strategies they used. The eye movement analysis showed longer dwell time and more frequent first fixations toward the reference number with practice, suggesting that participants relied more on the reference number to solve the task with practice. The strategy analysis revealed that with practice participants reduced their use of the approximate calculation strategy, which involves multiplying the rounded operands and comparing the product to the reference number, and increased their reliance on the sense of magnitude strategy which does not involve any calculation, but is grounded in the ANS. This was done especially for trials in which the reference number was far from the exact answer, thus exhibiting enhanced adaptivity in strategy choice with practice. PMID- 26553345 TI - Benzoxazepines Achieve Potent Suppression of IL-17 Release in Human T-Helper 17 (TH 17) Cells through an Induced-Fit Binding Mode to the Nuclear Receptor RORgamma. AB - RORgammat, an isoform of the retinoic acid-related orphan receptor gamma (RORc, RORgamma), has been identified as the master regulator of T-helper 17 (TH 17) cell function and development, making it an attractive target for the treatment of autoimmune diseases. Validation for this target comes from antibodies targeting interleukin-17 (IL-17), the signature cytokine produced by TH 17 cells, which have shown impressive results in clinical trials. Through focused screening of our compound collection, we identified a series of N-sulfonylated benzoxazepines, which displayed micromolar affinity for the RORgamma ligand binding domain (LBD) in a radioligand binding assay. Optimization of these initial hits resulted in potent binders, which dose-dependently decreased the ability of the RORgamma-LBD to interact with a peptide derived from steroid receptor coactivator 1, and inhibited the release of IL-17 secretion from isolated and cultured human TH 17 cells with nanomolar potency. A cocrystal structure of inverse agonist 15 (2-chloro-6-fluoro-N-(4-{[3 (trifluoromethyl)phenyl]sulfonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7 yl)benzamide) bound to the RORgamma-LBD illustrated that both hydrophobic interactions, leading to an induced fit around the substituted benzamide moiety of 15, as well as a hydrogen bond from the amide NH to His479 seemed to be important for the mechanism of action. This structure is compared with the structure of agonist 25 (N-(2-fluorophenyl)-4-[(4-fluorophenyl)sulfonyl]-2,3,4,5 tetrahydro-1,4-benzoxazepin-6-amine ) and structures of other known RORgamma modulators. PMID- 26553346 TI - The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View. AB - Carnosic acid (CA) and carnosol are the major diterpenes found in Rosmarinus officinalis (rosemary), a culinary spice. CA and carnosol account for over 90 % of its anti-oxidant activity in rosemary leaves. The diterpenes exert anti oxidant, anti-inflammatory, and anti-carcinogenic activities, and present neuroprotective effects in both in vitro and in vivo experimental models. In some cases, CA exerted protective effects upon neuronal cells more intensely than resveratrol or sulforaphane. Therefore, CA and carnosol demonstrate a potential pharmacological role for rosemary diterpenes in ameliorating mammalian brain redox status, among other parameters, as for instance the modulation of neuroinflammation. The aim of this review is to discuss the biological effects of CA and carnosol on neuronal and glial cells with focus on the mechanism of action of such diterpenes. PMID- 26553348 TI - Erratum to: Association Between the Single Nucleotide Polymorphism and the Level of Aquaporin-4 Protein Expression in Han and Minority Chinese with Inflammatory Demyelinating Diseases of the Central Nervous System. PMID- 26553347 TI - Dietary Patterns and Risk of Dementia: a Systematic Review and Meta-Analysis of Cohort Studies. AB - Dietary patterns and some dietary components have been linked with dementia. We therefore performed a meta-analysis of available studies to determine whether there is an association between diet and risk of dementia. We included eligible articles and estimated risk ratio (RR) with 95 % confidence intervals (95 % CIs). Finally, there were 43 trials that met the inclusion standard. Some food intake was related with decrease of dementia, such as unsaturated fatty acids (RR: 0.84, 95 % CI: [0.74-0.95], P = 0.006), antioxidants (RR: 0.87, 95 % CI: [0.77-0.98], P = 0.026), vitamin B (RR: 0.72, 95 % CI: [0.54-0.96], P = 0.026), and the Mediterranean diet (MeDi) (RR: 0.69, 95 % CI: [0.57-0.84], P < 0.001). Some material intakes were related with increase of dementia, such as aluminum (RR: 2.24, 95 % CI: [1.49-3.37], P < 0.001), smoking (RR: 1.43, 95 % CI: [1.15-1.77], P = 0.001), and low levels of vitamin D (RR: 1.52, 95 % CI: [1.17-1.98], P = 0.002). The effect of some materials needs further investigation, such as fish (RR: 0.79, 95 % CI: [0.59-1.06], P = 0.113), vegetables and fruits (RR: 0.46, 95 % CI: [0.16-1.32], P = 0.149), and alcohol (RR: 0.74, 95 % CI: [0.55- 1.01], P = 0.056). Thus, the MeDi and higher consumption of unsaturated fatty acids, antioxidants, and B vitamins decrease the risk of dementia while smoking and higher consumption of aluminum increase the risk of dementia. Low levels of vitamin D were associated with cognitive decline. The effect of fish, vegetables, fruits, and alcohol needs further investigation. The findings will be of great significance to guide people to prevent dementia. PMID- 26553351 TI - Sodium Acetate Coated Tenofovir-Loaded Chitosan Nanoparticles for Improved Physico-Chemical Properties. AB - PURPOSE: It is hypothesized that sodium acetate (SA) can be used for in situ coating of drug loaded chitosan NPs for improved physico-chemical properties. METHODS: Tenofovir (TFV) is used as a model drug. Uncoated chitosan NPs are prepared by ionic gelation. SA is generated in situ from half neutralization of acetic acid with sodium hydroxide, and coats chitosan NPs during freeze-drying. The NPs' physico-chemical properties [e.g., particle mean diameters (PMD) zeta potential (zeta), EE%, drug release profile, morphology] are characterized by dynamic light scattering, spectrophotometry, Korsmeyer-Peppas model, transmission electron microscopy (TEM), respectively. Melting point (MP), non-aqueous titration, Fourier transform infrared (FTIR) analysis, and powder X-ray diffractometry (XRD) pattern evaluate the SA coated chitosan NPs. The NPs' cytotoxicity on macrophages Raw 264.7 is assessed by neutral red, resazurin, nitrite oxide (NO) and cytokines assays. RESULTS: Collectively, FTIR, zeta, XRD, MP, and TEM data confirm that SA coats chitosan NPs. The PMD range is 136-348 nm (uncoated) and 171-379 nm (coated NPs). The zeta values range is +24.3-28.5 mV (uncoated) and 0.1-3.1 mV (coated NPs). The EE% ranges from 5.5 to 11.7% (uncoated NPs) and increased up to 86.3-92.7%(8-17-fold) after coating. The SA also prevents NPs aggregation during the freeze-drying and aqueous dispersion. The core-shell NPs exhibited a sustain release of TFV following anomalous transport mechanism (R(2) ~ 0.99). The coated NPs are non-cytotoxic (cell viability ~100%) and without any proinflammatory response. CONCLUSIONS: This SA coating chitosan NPs mechanism may be useful for (i) efficient encapsulation, (ii) stabilizing colloidal dispersions, (iii) controlling the release and solubility of bioactive agents. PMID- 26553349 TI - mGluR3 Activation Recruits Cytoplasmic TWIK-1 Channels to Membrane that Enhances Ammonium Uptake in Hippocampal Astrocytes. AB - TWIK-1 two-pore domain K+ channels are highly expressed in mature hippocampal astrocytes. While the TWIK-1 activity is readily detectable on astrocyte membrane, the majority of channels are retained in the intracellular compartments, which raises an intriguing question of whether the membrane TWIK-1 channels could be dynamically regulated for functions yet unknown. Here, the regulation of TWIK-1 membrane expression by Gi/Go-coupled metabotropic glutamate receptor 3 (mGluR3) and its functional impact on ammonium uptake has been studied. Activation of mGluR3 induced a marked translocation of TWIK-1 channels from the cytoplasm to the membrane surface. Consistent with our early observation that membrane TWIK-1 behaves as nonselective monovalent cation channel, mGluR3 mediated TWIK-1 membrane expression was associated with a depolarizing membrane potential (V M). As TWIK-1 exhibits a discernibly high permeability to ammonium (NH4+), a critical substrate in glutamate-glutamine cycle for neurotransmitter replenishment, regulation of NH4+ uptake capacity by TWIK-1 membrane expression was determined by response of astrocyte V M to bath application of 5 mM NH4Cl. Stimulation of mGluR3 potentiated NH4+-induced V M depolarization by ~30 % in wild type, but not in TWIK-1 knockout astrocytes. Furthermore, activation of mGluR3 mediated a coordinated translocation of TWIK-1 channels with recycling endosomes toward astrocyte membrane and the mGluR3-mediated potentiation of NH4+ uptake required a functional Rab-mediated trafficking pathway. Altogether, we demonstrate that the activation of mGluR3 up-regulates the membrane expression of TWIK-1 that in turn enhances NH4+ uptake in astrocytes, a mechanism potentially important for functional coupling of astrocyte glutamate-glutamine cycle with the replenishment of neurotransmitters in neurons. PMID- 26553352 TI - Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans. AB - BACKGROUND AND PURPOSE: The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess quantitatively the differences in the QTc prolonging effects of moxifloxacin between cynomolgus monkeys, dogs and humans. The impact of interspecies differences is also illustrated for a new candidate molecule. EXPERIMENTAL APPROACH: Pharmacokinetic data and ECG recordings from pre-clinical protocols in monkeys and dogs and from a phase I trial in healthy subjects were identified for the purpose of this analysis. A previously established Bayesian model describing the combined effect of heart rate, circadian variation and drug effect on the QT interval was used to describe the pharmacokinetic-pharmacodynamic relationships. The probability of a >= 10 ms increase in QT was derived as measure of the pro-arrhythmic effect. KEY RESULTS: For moxifloxacin, the concentrations associated with a 50% probability of QT prolongation >= 10 ms (Cp50) varied from 20.3 to 6.4 and 2.6 MUM in dogs, monkeys and humans, respectively. For NCE05, these values were 0.4 MUM vs 2.0 MUM for monkeys and humans, respectively. CONCLUSIONS AND IMPLICATIONS: Our findings reveal significant interspecies differences in the QT-prolonging effect of moxifloxacin. In addition to the dissimilarity in pharmacokinetics across species, it is likely that differences in pharmacodynamics also play an important role. It appears that, regardless of the animal model used, a translation function is needed to predict concentration-effect relationships in humans. PMID- 26553353 TI - Screening and In Vitro Evaluation of Mucoadhesive Thermoresponsive System Containing Methylene Blue for Local Photodynamic Therapy of Colorectal Cancer. AB - PURPOSE: Photodynamic therapy (PDT) with methylene blue (MB) constitutes a potentially useful modality for colorectal cancer treatment. The limitations of the formulations containing MB are problems of administration and the inability to get the closeness contact at the site during the appropriate residence time. Present study aimed to develop and characterize mucoadhesive thermoresponsive system containing MB designed as platform for colorectal cancer therapy. METHODS: Formulations composed of different amounts of poloxamer 407 (Polox), Carbopol 934P (Carb), and MB were developed and characterized as rheological, compressional, mucoadhesive and syringeability properties, toxicity, photodynamic action, in vitro MB release profile, and ex vivo MB intestinal permeation. RESULTS: The different compositions resulted in formulations with distinctive macroscopic characteristics and wide range of gelation temperatures. The compressional flow, mucoadhesive, syringeability, and rheological properties were significantly influenced by temperature and/or composition. The MB release from formulation was governed by anomalous transport. In addition, it was observed that MB permeated the intestinal membrane; the formulation possesses photodynamic activity and low toxicity. CONCLUSIONS: The data obtained from the system composed of 20% Polox, 0.15% Carb, and 0.25% MB indicated a potentially functional role in PDT of the colorectal cancer and suggest it is worthy of clinical evaluation. PMID- 26553354 TI - Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions. AB - PURPOSE: To develop a model predicting movement of non-disintegrating single unit dosage forms (or "tablet") through the gastrointestinal tract and characterizing the effect of food intake, based on Magnetic Marker Monitoring data, allowing real-time location of a magnetically labeled formulation. METHODS: Five studies including 30 individuals in 94 occasions under 3 food status were considered. The mean residence time (MRT) of the tablet and the effect of food intake in proximal (PS) and distal stomach (DS), small intestine (SI), ascending (AC), transverse (TC) and descending colon (DC) were estimated using a Markov model for probabilities of movement. RESULTS: Under fasting conditions, tablet MRTs were 9.4 min in PS, 10.4 in DS, 246 in SI, 545 in AC, 135 in TC, and 286 in DC. A meal taken simultaneous to tablet intake prolonged tablet MRT to 99 min in PS and to 232 in DS; probability of gastric emptying increased of 89% each hour from 2.25 h after meal. The effect of a gastroileac reflex, caused by a secondary meal, accelerated the transit from terminal SI to AC. CONCLUSION: This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation. PMID- 26553355 TI - Glucose-Based Mesoporous Carbon Nanospheres as Functional Carriers for Oral Delivery of Amphiphobic Raloxifene: Insights into the Bioavailability Enhancement and Lymphatic Transport. AB - PURPOSE: Oral therapy with raloxifene (RXF), an amphiphobic drug for remedy of the postmenopausal osteoporosis and estrogen-dependent breast cancer, is less effective due to its poor bioavailability (2% or so). This work aimed to devise mesoporous carbon nanospheres (MCNs) for oral delivery of RXF and evaluate their performance in bioavailability enhancement and lymphatic transport. METHODS: Glucose-based MCNs were fabricated by hydrothermal reaction followed by high temperature activation. RXF-loaded MCNs (RXF-MCNs) were prepared by solvent diffusion/high-pressure homogenization and stabilized by phospholipid. RXF-MCNs were fully characterized by particle size, morphology, in vitro drug release and metabolism, in vivo pharmacokinetics and lymphatic transport, and ex vivo fluorescent imaging. RESULTS: The prepared RXF-MCNs were 230 nm around in particle size, showing high entrapment efficiency (95.35%) and satisfactory physical stability. The oral bioavailability of RXF was enhanced by 2.07 folds through MCNs compared with RXF suspensions in rats. It was shown that reduced intestinal metabolism due to entrapment into MCNs, active transcellular uptake and increased lymphatic transport were responsible for enhanced bioavailability as a result of transport improvement. CONCLUSIONS: The results suggest that MCNs are suitable nanocarriers for oral delivery of poorly bioavailable RXF. PMID- 26553356 TI - [Clinical assessment of pain in Spanish Neonatal Intensive Care Units]. AB - INTRODUCTION: Clinical scales are currently the best method to assess pain in the neonate, given the impossibility of self-report in this age group. A study is designed with the aim of determining the current practices as regards the clinical assessment of pain in Spanish Neonatal Units and the factors associated with the use of clinical scales. METHODS: A prospective longitudinal observational study was conducted. A total of 30 Units participated and 468 neonates were included. RESULTS: Only 13 Units (43.3%) had pain assessment protocols. Pain was evaluated with a scale in 78 neonates (16.7%, 95% CI; 13.1 20.1) and the mean number of pain assessments per patient and per day was 2.3 (Standard Deviation; 4.8), with a median of 0.75. Of the total number of 7,189 patient-days studied, there was at least one pain assessment in 654 (9.1%). No pain assessment was performed with a clinical scale on any patient in 20 (66.7%) Units. Among those that did, a wide variation was observed in the percentage of patients in whom pain was assessed, as well as in the scales used. The CRIES (C Crying; R-Requires increased oxygen administration; I-Increased vital signs; E Expression; S-Sleeplessness) scale was that used in most Units. In the multivariate analysis, only invasive mechanical ventilation was associated with receiving a pain assessment with a scale (OR 1.46, P=.042). DISCUSSION: The majority of neonates admitted into Intensive Care in Spain do not receive a pain assessment. Many units still do not routinely use clinical scales, and there is a wide variation between those that do use them. These results could serve as a basis for preparing national guidelines as regards pain in the neonate. PMID- 26553357 TI - [Colour density spectral array of bilateral bispectral index in status epilepticus]. PMID- 26553358 TI - Correlation of soil organic carbon and nutrients (NPK) to soil mineralogy, texture, aggregation, and land use pattern. AB - This work investigates the correlations existing among soil organic carbon (C), nitrogen (N), phosphorous (P), potassium (K), and physicochemical properties like clay mineralogy, textural components, soil aggregation, and land use pattern. Seven different locations were chosen in the tropical rainforest climate region of Assam, India, for the work. The soil texture classifications were clay, sandy clay loam, and sandy loam with mixed clay mineralogy consisting of tectosilicates and phylosilicates. Two distinct compositions of total Fe/Al oxides>=11.5 and <10.8% were observed along with two distinct groups of water stable soil aggregates of mean weight diameter~6.42 and <=3.26 mm. The soil clay and sand had positive and negative contributions respectively to the soil organic carbon (SOC) protection, which was observed to be dependent on lesser sand content, higher silt+clay content, and the presence of higher percentages of total Fe/Al oxides. Soil clay mineralogy suggested that the mineral, chlorite, favored retention of higher SOC content in a particular site. Under similar climatic and mineralogical conditions, both natural and anthropogenic soil disturbances destabilized SOC protection through SOM mineralization and soil aggregate destabilization as indicated by SOC protective capacity studies. Urbanization resulting in soil compaction contributed to enhanced SOC level through increased contact between the occluded organic carbon and the soil mineralogical constituents. PMID- 26553359 TI - miR-198 targets SHMT1 to inhibit cell proliferation and enhance cell apoptosis in lung adenocarcinoma. AB - MiR-198 is involved in tumorigenesis, migration, invasion, and metastasis of various malignant cancers. However, the exact expression levels of miR-198 and the molecular mechanism underlying its role in lung adenocarcinoma require further exploration. In this study, quantitative real-time PCR was applied to study miR-198 and serine hydroxymethyltransferase 1 (SHMT1) expression in 47 paired lung adenocarcinoma tissues and adjacent nontumor lung tissues. Clinicopathological characters were analyzed. Pearson's correlation analysis was used to detect the relationship between miR-198 and SHMT1 expression. The function of miR-198 was explored by measuring cell proliferation, cell apoptosis, and the cell-cycle in vitro and in vivo. The target gene of miR-198 was certified using dual luciferase report assay. We found that in lung adenocarcinoma, miR-198 was significantly downregulated and SHMT1 was inversely upregulated. A strong negative correlation was noticed between miR-198 and SHMT1 expression. Further analysis revealed that miR-198 expression was associated with TNM stage and lymph node metastasis. Upregulated miR-198 could inhibit cell proliferation, enhance cell apoptosis, and lead to cell-cycle arrest in lung adenocarcinoma, which showed a more effective alteration than SHMT1 siRNA. Moreover, we identified SHMT1 as a target gene of miR-198. In conclusion, miR-198 suppressed proliferation of lung adenocarcinoma cells both in vitro and in vivo by directly targeting SHMT1. miR-198 may be a potential therapeutic target for lung adenocarcinoma in the near future. PMID- 26553360 TI - miR-339-5p inhibits migration and invasion in ovarian cancer cell lines by targeting NACC1 and BCL6. AB - This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression. PMID- 26553361 TI - FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target. AB - The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression. PMID- 26553362 TI - Isocitrate dehydrogenase 2 inhibits gastric cancer cell invasion via matrix metalloproteinase 7. AB - Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase and has been found to be a tumor suppressor in several types of tumors. However, the roles of IDH2 in hepatocellular carcinoma (GC) as well as underlying mechanisms remain unknown. Here, the IDH2 and matrix metalloproteinase 7 (MMP7) levels in the specimens from 30 GC patients were investigated by Western blot and ELISA, respectively. Their relationship was examined by correlation analyses. Patient survival with high IDH2 levels and low IDH2 levels was compared. IDH2 levels, and MMP7 levels were modified in a human GC cell line. The effects of IDH2 or MMP7 modulation on the expression of each other were analyzed. The dependence of nuclear factor kappaB (NF-kappaB) signaling was examined using a specific inhibitor. We found that the IDH2 levels significantly decreased in GC, and were even lower in GC with metastases, compared to those without metastases. IDH2 levels inversely correlated with MMP7 levels in GC. GC patients with low IDH2 had lower 5-year survival. MMP7 levels did not regulate IDH2 levels, while IDH2 inhibited MMP7 levels in GC cells, in a NF-kappaB signaling dependent manner. Together, these data suggest that IDH2 may be a tumor suppressor in that its loss may promote malignant progression of GC via NF-kappaB dependent increases in MMP7 activity. PMID- 26553364 TI - Doctor is suspended for aborting fetus because it was female. PMID- 26553363 TI - Evaluation of prognostic factors in localized high-grade undifferentiated pleomorphic sarcoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology. AB - Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19-90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6-30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2-160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision. PMID- 26553365 TI - Carbonic Anhydrase 9 mRNA/microRNA34a Interplay in Hypoxic Human Mammospheres. AB - The hypoxic environment is a crucial component of the cancer stem cell niche and it is capable of eliciting stem cell features in cancer cells. We previously reported that SNAI2 up-regulates the expression of Carbonic Anhydrase iso-enzyme 9 (CA9) in hypoxic MCF7 cells. Here we show that SNAI2 down-regulates miR34a expression in hypoxic MCF7 cell-derived mammospheres. Next, we report on the capability of miR34a to decrease CA9 mRNA stability and CA9 protein expression. We also convey that the over-expression of cloned CA9-mRNA-3'UTR increases the mRNA half-life and protein levels of two miR34a targets JAGGED1 and NOTCH3. The data here reported shows that the SNAI2-dependent down-regulation of miR34a substantially contributes to the post-transcriptional up-regulation of CA9, and that CA9-mRNA-3'UTR acts as an endogenous microRNA sponge. We conclude that CA9/miR34 interplay shares in the hypoxic regulation of mammospheres and therefore, may play a relevant role in the hypoxic breast cancer stem cell niche. PMID- 26553367 TI - Segregated Pt on Pd nanotubes for enhanced oxygen reduction activity in alkaline electrolyte. AB - Nanoscaled Pt domains were integrated with Pd nanotubes via vapor deposition to yield a highly active electrocatalyst for the oxygen reduction reaction (ORR) in alkaline media. The surface-area-normalized ORR activity of these bi-metallic Pt on-Pd nanotubes (PtPdNTs) was nearly 6* the corresponding carbon-supported Pt nanoparticle (Pt/C) activity at 0.9 V vs. RHE (1.5 vs. 0.24 mA cmmetal(-2), respectively). Furthermore, the high specific activity of the PtPdNTs was achieved without sacrificing mass-normalized activity, which is more than twice that of Pt/C (0.333 A mgPtPdNT(-1)vs. 0.141 A mgPt/C(-1)) and also greater than that of Pd/C (0.221 A mgPd/C(-1)). We attribute the enhancements in specific and mass activity to modifications of the segregated Pt electronic structure and to nanoscale porosity, respectively. PMID- 26553366 TI - Sex differences in DNA methylation assessed by 450 K BeadChip in newborns. AB - BACKGROUND: DNA methylation is an important epigenetic mark that can potentially link early life exposures to adverse health outcomes later in life. Host factors like sex and age strongly influence biological variation of DNA methylation, but characterization of these relationships is still limited, particularly in young children. METHODS: In a sample of 111 Mexican-American subjects (58 girls , 53 boys), we interrogated DNA methylation differences by sex at birth using the 450 K BeadChip in umbilical cord blood specimens, adjusting for cell composition. RESULTS: We observed that ~3% of CpG sites were differentially methylated between girls and boys at birth (FDR P < 0.05). Of those CpGs, 3031 were located on autosomes, and 82.8% of those were hypermethylated in girls compared to boys. Beyond individual CpGs, we found 3604 sex-associated differentially methylated regions (DMRs) where the majority (75.8%) had higher methylation in girls. Using pathway analysis, we found that sex-associated autosomal CpGs were significantly enriched for gene ontology terms related to nervous system development and behavior. Among hits in our study, 35.9% had been previously reported as sex associated CpG sites in other published human studies. Further, for replicated hits, the direction of the association with methylation was highly concordant (98.5-100%) with previous studies. CONCLUSIONS: To our knowledge, this is the first reported epigenome-wide analysis by sex at birth that examined DMRs and adjusted for confounding by cell composition. We confirmed previously reported trends that methylation profiles are sex-specific even in autosomal genes, and also identified novel sex-associated CpGs in our methylome-wide analysis immediately after birth, a critical yet relatively unstudied developmental window. PMID- 26553368 TI - The "different face" of esophageal cancer: cutaneous manifestation of visceral malignancies. AB - Squamous cell carcinoma is the most common type of neoplasm of the esophagus with global incidence. Its early symptoms are often nonspecific as the disease could be detected only when metastases in various organs are already presented. Esophageal metastases present an extremely small part from all cutaneous metastases as the real incidence of cutaneous metastases due to cancer of the esophagus account for 0.5-9 % and only a small part of them are reported and rarely involve the facial region. Despite this, cutaneous metastases may be the first sign of malignancy of the esophagus, which immediately determined the worst prognosis and fatal outcome in these patients. Average survival prognosis at the time of diagnosis of esophageal carcinoma in stage IV is 4-6 months, while the survival-associated expectations in cases of associated skin lesions manifestation is 4 months. We present a rare case of esophagus carcinoma in advanced stage, presented with severe cutaneous metastasis in the face region, accompanied by heavy blood coughing and hematemesis, which led to fatal outcome in the reported patient. The incidence of cutaneous metastases due to this visceral malignancy is discussed, as we highlight the frequency of metastases as a first clinical sign in esophageal cancer. The mortality rate is high due to the advanced stage of progression of the disease or presented metastases spread at the time of diagnosis, while treatment-related mortality accounts 10.3 %. PMID- 26553369 TI - A tutorial on Bayesian bivariate meta-analysis of mixed binary-continuous outcomes with missing treatment effects. AB - Bivariate random-effects meta-analysis (BVMA) is a method of data synthesis that accounts for treatment effects measured on two outcomes. BVMA gives more precise estimates of the population mean and predicted values than two univariate random effects meta-analyses (UVMAs). BVMA also addresses bias from incomplete reporting of outcomes. A few tutorials have covered technical details of BVMA of categorical or continuous outcomes. Limited guidance is available on how to analyze datasets that include trials with mixed continuous-binary outcomes where treatment effects on one outcome or the other are not reported. Given the advantages of Bayesian BVMA for handling missing outcomes, we present a tutorial for Bayesian BVMA of incompletely reported treatment effects on mixed bivariate outcomes. This step-by-step approach can serve as a model for our intended audience, the methodologist familiar with Bayesian meta-analysis, looking for practical advice on fitting bivariate models. To facilitate application of the proposed methods, we include our WinBUGS code. As an example, we use aggregate level data from published trials to demonstrate the estimation of the effects of vitamin K and bisphosphonates on two correlated bone outcomes, fracture, and bone mineral density. We present datasets where reporting of the pairs of treatment effects on both outcomes was 'partially' complete (i.e., pairs completely reported in some trials), and we outline steps for modeling the incompletely reported data. To assess what is gained from the additional work required by BVMA, we compare the resulting estimates to those from separate UVMAs. We discuss methodological findings and make four recommendations. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553370 TI - Strain induced piezoelectric effect in black phosphorus and MoS2 van der Waals heterostructure. AB - The structural, electronic, transport and optical properties of black phosphorus/MoS2 (BP/MoS2) van der Waals (vdw) heterostructure are investigated by using first principles calculations. The band gap of BP/MoS2 bilayer decreases with the applied normal compressive strain and a semiconductor-to-metal transition is observed when the applied strain is more than 0.85 A. BP/MoS2 bilayer also exhibits modulation of its carrier effective mass and carrier concentration by the applied compressive strain, suggesting that mobility engineering and good piezoelectric effect can be realized in BP/MoS2 heterostructure. Because the type-II band alignment can facilitate the separation of photo-excited electrons and holes, and it can benefit from the great absorption coefficient in ultra-violet region, the BP/MoS2 shows great potential to be a very efficient ultra-violet photodetector. PMID- 26553371 TI - A Fluorescent Imaging Probe Based on a Macrocyclic Scaffold That Binds to Cellular EpCAM. AB - Here, we report a fluorescent probe based on a macrocyclic peptide scaffold that specifically stains EpCAM-expressing MCF7 cells. The 14-mer macrocyclic peptide binding to the extracellular domain of EpCAM with a dissociation constant in the low nM range (1.7 nM) was discovered using the random non-standard peptide integrated discovery system. Notably, this probe containing a fluorescence tag is less than 3000 Da in total and able to visualize nearly every live cell under high cell-density conditions, which was not achieved by the conventional mAb staining method. This suggests that the molecular probe based on the compact macrocyclic scaffold has great potentials as an imaging tool for the EpCAM biomarker as well as a delivery vehicle for drug conjugates. PMID- 26553372 TI - Hyperhomocysteinemia predicts renal function decline: a prospective study in hypertensive adults. AB - Hyper-homocysteinemia (HHcy) is associated with microalbuminuria and glomerular injury in general and diabetic populations. However, HHcy's role in hypertensive patients was not studied. We investigated whether HHcy is an independent risk factor for renal function decline and development of chronic kidney disease (CKD) in hypertensive men and women. This was a community-based prospective cohort study of 2,387 hypertensive adults without CKD at baseline, with a mean follow-up of 4.4 years. Baseline and follow-up levels of plasma Hcy, folate, vitamin B12, blood pressure and other pertinent covariables were obtained. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/per 1.73 m(2) and an eGFR decline rate >1 ml/min/per 1.73 m(2)/year. There was a graded association between Hcy tertiles and eGFR decline. Subjects in the 3(rd) tertile of Hcy levels had an accelerated rate of eGFR decline and an increased risk of incident CKD, as compared with those in the 1st tertile, after adjusting for age, gender, baseline diabetes, SBP, BMI, smoking, dyslipidemia, eGFR, folate and vitamin B12 levels. In conclusion, in this prospective cohort of Chinese hypertensive adults, elevated baseline plasma Hcy can serve as an independent biomarker to predict renal function decline and incident CKD. PMID- 26553373 TI - Training of Working Memory Impacts Neural Processing of Vocal Pitch Regulation. AB - Working memory training can improve the performance of tasks that were not trained. Whether auditory-motor integration for voice control can benefit from working memory training, however, remains unclear. The present event-related potential (ERP) study examined the impact of working memory training on the auditory-motor processing of vocal pitch. Trained participants underwent adaptive working memory training using a digit span backwards paradigm, while control participants did not receive any training. Before and after training, both trained and control participants were exposed to frequency-altered auditory feedback while producing vocalizations. After training, trained participants exhibited significantly decreased N1 amplitudes and increased P2 amplitudes in response to pitch errors in voice auditory feedback. In addition, there was a significant positive correlation between the degree of improvement in working memory capacity and the post-pre difference in P2 amplitudes. Training-related changes in the vocal compensation, however, were not observed. There was no systematic change in either vocal or cortical responses for control participants. These findings provide evidence that working memory training impacts the cortical processing of feedback errors in vocal pitch regulation. This enhanced cortical processing may be the result of increased neural efficiency in the detection of pitch errors between the intended and actual feedback. PMID- 26553374 TI - Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy. AB - OBJECTIVE: Myocardial infarction (MI) is a frequent complication of carotid endarterectomy (CEA), yet most events are silent. Routine post-operative monitoring of cardiac troponin was implemented to facilitate timely recognition of MI and stratify high risk patients. The aim was to evaluate the incidence of troponin elevation after CEA and its association with adverse cardiovascular events. METHODS: This analysis included patients >=60 years old who underwent CEA, whose troponin-I levels were routinely monitored post-operatively and were included in a cohort study that assessed clinical outcomes. A clinical troponin cutoff of 60 ng/L was used. The primary endpoint was the composite of MI, stroke, and cardiovascular death. Secondary endpoints were MI, stroke, coronary intervention, cardiovascular death, and all cause death. RESULTS: 225 consecutive patients were included in the analysis. Troponin elevation occurred in 34 patients (15%) and a post-operative MI was diagnosed in eight patients. After a median follow up of 1.8 years (IQR 1.0-2.6), the primary endpoint occurred in 29% of patients with troponin elevation versus 6.3% without (HR 5.6, 95% CI 2.4-13), MI in 24% versus 1.6% (HR 18.0, 95% CI 4.7-68), stroke in 5.9% versus 4.2% (HR 1.4, 95% CI 0.3-6.7), coronary intervention in 5.9% versus 2.6% (HR 2.7, 95% CI 0.5-14), cardiovascular death in 5.9% versus 0.5% (HR 11.8, 95% CI 1.1-131), and all cause death in 15% versus 5.8% (HR 3.0, 95% CI 1.0-8.7), respectively. Incidences of the primary endpoint and all cause mortality in patients with a post-operative MI versus "troponin only" were 25% versus 7.7% and 25% versus 12%, respectively. CONCLUSION: Troponin elevation after CEA occurred in 15% of patients. The incidence of adverse cardiovascular events was significantly higher in patients with troponin elevation, which was mainly attributable to silent non ST segment elevation MIs that occurred in the early post-operative phase. PMID- 26553375 TI - Swelling in the thigh. PMID- 26553376 TI - Nasal continuous positive airway pressure versus nasal intermittent positive pressure ventilation within the minimally invasive surfactant therapy approach in preterm infants: a randomised controlled trial. AB - OBJECTIVE: To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive-pressure ventilation (NIPPV) as the initial respiratory support within the minimally invasive surfactant therapy (MIST) approach in preterm infants with respiratory distress syndrome. DESIGN: Prospective, randomised controlled study. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND INTERVENTIONS: This study enrolled 200 preterm infants with a gestational age of 26-32 weeks who showed signs of respiratory distress but did not require intubation in the delivery room. Surfactant therapy was performed using the MIST approach in the patients who met the criteria for surfactant administration. MAIN OUTCOME MEASURES: The primary outcomes were a need for intubation within the first 72 h of life and a surfactant requirement. RESULTS: The infants in the study displayed similar characteristics at birth. Fewer infants in the NIPPV group required surfactant therapy (38% vs 60%; p=0.002) or invasive ventilation during the first 72 h of life (13% vs 29%; p=0.005), and NIPPV reduced the rate of moderate-to-severe bronchopulmonary dysplasia (BPD) (7% vs 16%; p=0.046). Multivariate logistic regression analysis showed that NIPPV support (OR: 0.36, 95% CI 0.17 to 0.76; p=0.008) and higher gestational age (OR: 0.76, 95% CI 0.59 to 0.98; p=0.041) reduced the need for invasive ventilation within the first 72 h of life. Surfactant requirement was also decreased with NIPPV support (OR: 0.39, 95% CI 0.22 to 0.71; p=0.002). However, there was no impact on BPD, based on the multivariate analysis. CONCLUSIONS: In infants born at 26-32 weeks' gestation, NIPPV reduced the need for invasive ventilation and the surfactant requirement within the MIST approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov under identifier NCT01741129. PMID- 26553378 TI - A rise of ploidy level influences the rate of cytomixis in tobacco male meiosis. AB - The effect of plant ploidy level on the rate of cytomixis in microsporogenesis has been analyzed with the help of a unique model, the collection of tobacco plants of different ploidies (2n = 2x = 24, 4x = 48, 6x = 72, and 8x = 96). As has been shown, the rate of cytomixis proportionally increases in 6x and 8x cytotypes, being rather similar in 2x and 4x plants. The rate of cytomixis is highly variable, differing even in the genetically identical plants grown under the same conditions. The cytological pattern of cytomixis in the microsporogenesis of control 4x plants has been compared with the corresponding patterns of 2x, 6x, and 8x plants. Involvement of cytomixis in production of unreduced gametes and stabilization of the newly formed hybrid and polyploidy genomes is discussed. PMID- 26553379 TI - Pioneer neurons of the antennal nervous system project to protocerebral pioneers in the grasshopper Schistocerca gregaria. AB - The twin nerve tracts of the antenna of the grasshopper Schistocerca gregaria are established early in embryogenesis by sibling pairs of pioneers which delaminate from the epithelium into the lumen at the antennal tip. These cells can be uniquely identified via their co-expression of the neuronal labels horseradish peroxidase and the lipocalin Lazarillo. The apical pioneers direct axons toward the antennal base where they encounter guidepost-like cells called base pioneers which transiently express the same molecular labels as the apical pioneers. To what extent the pioneer growth cones then progress into the brain neuropil proper, and what their targets there might be, has remained unclear. In this study, we show that the apical antennal pioneers project centrally beyond the antennal base first into the deutocerebral, and then into the protocerebral brain neuropils. In the protocerebrum, we identify their target circuitry as being identified Lazarillo-positive cells which themselves pioneer the primary axon scaffold of the brain. The apical and base antennal pioneers therefore form part of a molecularly contiguous pathway from the periphery to an identified central circuit of the embryonic grasshopper brain. PMID- 26553380 TI - MicroRNA expression during demosponge dissociation, reaggregation, and differentiation and a evolutionarily conserved demosponge miRNA expression profile. AB - Demosponges share eight orthologous microRNAs (miRNAs), with none in common with Bilateria. Biological functions of these demosponge miRNAs are unknown. Bilaterian miRNAs are key regulators of cellular processes including cell cycle, differentiation, and metabolism. Resolving if demosponge miRNAs participate in such biological functions will provide clues whether these functions are convergent, evidence on the mode of evolution of cellular developmental processes. Here, a quantitative PCR (qPCR) assay was developed and used to test for differential miRNA expression during dissociation and reaggregation in Spongosorites, compare expression profiles between choanosome and cortex in Spongosorites, and compare undifferentiated gemmules to differentiated juveniles in Ephydatia. During Spongosorites dissociation and reaggregation, miRNA expression showed a global decrease in expression across a range of reaggregating cell densities. miRNA differential response could be related to various general cellular responses, potentially related to nutrient-poor conditions of the minimal artificial seawater media, stress response from tissue dissociation, or loss of cell-cell or cell-matrix contact. In Ephydatia, overall increase in miRNA expression in gemmule-hatched stage 4/5 juveniles relative to gemmules is observed, indicating that increased miRNA expression may be related to increased cellular activity such as migration, cell cycle, and/or differentiation. Observed differential miRNA expression of miRNA during dissociation in Spongosorites (lowered global expression), and during activation, and differentiation of Ephydatia gemmules (increased global expression) could indicate that miRNA expression is associated with cell cycle, differentiation, or metabolism pathways. Interspecies comparison was performed, results indicating that orthologous miRNAs share similar relative expression pattern between the four species tested (Spongosorites, Cinachyrella, Haliclona, and Ephydatia), demonstrating and evolutionarily conserved miRNA expression profile across Demospongia. While these results do not elucidate specific molecular and cellular pathways, together they provide a broad survey of miRNA expression in demosponge systems. PMID- 26553381 TI - Cellular and viral determinants of retroviral nuclear entry. AB - Retroviruses must integrate their cDNA into the host genome to generate proviruses. Viral DNA-protein complexes interact with cellular proteins and produce pre-integration complexes, which carry the viral genome and cross the nuclear pore channel to enter the nucleus and integrate viral DNA into host chromosomal DNA. If the reverse transcripts fail to integrate, linear or circular DNA species such as 1- and 2-long terminal repeats are generated. Such complexes encounter numerous cellular proteins in the cytoplasm, which restrict viral infection and protect the nucleus. To overcome host cell defenses, the pathogens have evolved several evasion strategies. Viral proteins often contain nuclear localization signals, allowing entry into the nucleus. Among more than 1000 proteins identified as required for HIV infection by RNA interference screening, karyopherins, cleavage and polyadenylation specific factor 6, and nucleoporins have been predominantly studied. This review discusses current opinions about the synergistic relationship between the viral and cellular factors involved in nuclear import, with focus on the unveiled mysteries of the host-pathogen interaction, and highlights novel approaches to pinpoint therapeutic targets. PMID- 26553383 TI - Ranking prescribed pharmaceuticals in terms of environmental risk: Inclusion of hospital data and the importance of regular review. AB - A newly available dataset on pharmaceuticals used in Scottish hospitals enabled an environmental risk assessment that includes hospital consumption of pharmaceuticals, as previous United Kingdom rankings have been based on community prescriptions only. Although health and the environment are devolved issues for the Scottish government, it is merited to consider a Scottish ranking separately; regional differentiation is particularly relevant in the spatial context of the European Commission's Water Framework Directive. Nine pharmaceuticals are identified as having a risk quotient greater than 1. Four of these, the antibacterials piperacillin, tazobactam, flucloxacillin, and ciprofloxacin, had high hospital contributions and had not been highlighted previously in rankings based on community prescriptions. Some drugs with a risk quotient < 0.1 are used almost exclusively in hospitals and could be more concentrated near effluents carrying hospital wastewater, where they may be of local concern. Although treating hospital effluents separately is a policy option, specifically including hospital consumption is important. Continually increasing the availability of ecotoxicological data and trends in consumption further contributes to a substantially different prioritization than in previous rankings. This leads the authors to conclude that regular review of risk is necessary. PMID- 26553384 TI - Atomic structure and composition distribution in wetting layers and islands of germanium grown on silicon (001) substrates. AB - We present a comprehensive structural investigation of the Ge wetting layer (WL) and island growth on Si(001) substrates by a combination of AFM, high resolution transmission electron microscopy and the energy-differential coherent Bragg rod analysis (COBRA) x-ray method. By considering the influence of the initial Si surface morphology on the deposited Ge, these techniques provide quantitative information on the Ge content and its distribution, in particular within the WL which plays a crucial role in the formation of epitaxial nanostructures. In the WL, the Ge content was found to be above 80% for our growth conditions. Furthermore, from the digital analysis of high-resolution transmission electron microscope images, quantitative information on the strain relaxation is obtained, which complements the COBRA analysis of the Ge distribution and content in these nanostructures. PMID- 26553382 TI - Occurrence of viable, red-pigmented haloarchaea in the plumage of captive flamingoes. AB - Flamingoes (Phoenicopterus spp.) whose plumage displays elegant colors, inhabit warm regions close to the ocean throughout the world. The pink or reddish color of their plumage originates from carotenoids ingested from carotenoid-abundant food sources, since flamingoes are unable to synthesize these compounds de novo. In this study, viable red-colored archaeal strains classified as extremely halophilic archaea (i.e., haloarchaea) and belonging to the genera Halococcus and Halogeometricum were isolated from the plumage of flamingoes in captivity. Detailed analysis for haloarchaeal community structure in flamingo feathers based on metagenomic data identified several haloarchaeal genera and unclassified sequences of the class Halobacteria at the genus level. Carotenoid pigment analyses showed that a bacterioruberin precursor carotenoid in haloarchaea was identical to one of the pigments found in flamingo plumage. To the best of our knowledge, this is the first report of viable extremophilic archaea in avian plumage, thus contributing to our understanding of the ecology of haloarchaea. The potential influence of haloarchaea as an environmental factor determining avian plumage coloration should be investigated in further studies. PMID- 26553385 TI - Is somatosensory amplification a risk factor for an increased report of side effects? Reference data from the German general population. AB - OBJECTIVE: The study investigates the association between somatosensory amplification and the reporting of side effects. It establishes a German version of the Somatosensory Amplification Scale and examines its psychometric properties in a representative sample of the German population. METHODS: Sample size was 2.469, with 51% taking any medication. Participants answered the Somatosensory Amplification Scale, Generic Assessment of Side Effects Scale, and indicated whether they were taking any medication and the type of medication. Correlational analysis and binary logistic regression were performed. RESULTS: When examining a subsample reporting both medication intake and general bodily symptoms, participants higher in somatosensory amplification rated more of their general bodily symptoms as medication-attributed side effects. However, somatosensory amplification scores were not associated with the intake of any type of medication. In the overall sample, higher somatosensory amplification scores were associated with an increased report of bodily symptoms. Additionally, participants with higher somatosensory amplification reported intake of a greater number of different medications. The psychometric properties of the translated scale were good, and previously established associations of somatosensory amplification with demographic variables (age, sex) were replicated. CONCLUSION: Results suggest a possible attributional bias concomitant to somatosensory amplification which in turn may increase the reporting of side effects after medication intake. PMID- 26553386 TI - Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation. AB - The induction of innate and adaptive immunity is essential for controlling viral infections. Limited or overwhelming innate immunity can negatively impair the adaptive immune response. Therefore, balancing innate immunity separately from activating the adaptive immune response would result in a better antiviral immune response. Recently, we demonstrated that Usp18-dependent replication of virus in secondary lymphatic organs contributes to activation of the innate and adaptive immune responses. Whether specific mechanisms can balance innate and adaptive immunity separately remains unknown. In this study, using lymphocytic choriomeningitis virus (LCMV) and replication-deficient single-cycle LCMV vectors, we found that viral replication of the initial inoculum is essential for activating virus-specific CD8(+) T cells. In contrast, extracellular distribution of virus along the splenic conduits is necessary for inducing systemic levels of type I interferon (IFN-I). Although enforced virus replication is driven primarily by Usp18, B cell-derived lymphotoxin beta contributes to the extracellular distribution of virus along the splenic conduits. Therefore, lymphotoxin beta regulates IFN-I induction independently of CD8(+) T-cell activity. We found that two separate mechanisms act together in the spleen to guarantee amplification of virus during infection, thereby balancing the activation of the innate and adaptive immune system. PMID- 26553388 TI - Plantar approach for Morton's neuroma: An effective technique for primary excision. AB - BACKGROUND: Morton's neuroma is a common cause of inter-metatarsal foot pain. Surgical excision is generally indicated when non-operative measures have been unsuccessful; various surgical techniques have been described in the literature for excision, with no consensus on the overall ideal surgical approach. AIM: To assess patient outcomes and complications following plantar surgical approach to neurectomy in a consecutive series of patients. METHOD: An analysis of consecutive patients undergoing excision of Morton's neuroma using a plantar approach by a single surgeon over a 12 month period. Pre- and post-operative AOFAS and VAS scores were completed during outpatient visits. RESULTS: 20 patients were included in the study, with pre-operative confirmation of a soft tissue mass on ultrasound scan. All patients demonstrated improvement in their post-operative functional scores; 2 patients (10%) did not have full resolution of their symptoms post-operatively. Mean AOFAS scores improved from 39 to 80 post operatively and VAS from 40 to 92. No patients had wound complications or scar pain. CONCLUSION: Neurectomy performed via a plantar approach provides good exposure, adequate soft tissue healing, with rapid resolution of pain and return to normal activities post-operatively. PMID- 26553387 TI - Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients. AB - INTRODUCTION: TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients. MATERIAL AND METHOD: The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects. RESULTS: It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (chi (2) = 9.92, p = 0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95 % CI: 1.22-2.77), risk ratio 1.34 (95 % CI: 1.11-1.63), p value 0.003], HER2/neu status (p = 0.01) and distant metastasis (p = 0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (chi (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04). CONCLUSION: Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53. PMID- 26553389 TI - Improved prognosis for patients with oral cavity squamous cell carcinoma: Analysis of the National Cancer Database 1998-2006. AB - BACKGROUND: Improvements in prognosis have been reported for oral cavity squamous cell carcinoma (OCSCC) in international cohorts. We sought to quantify improvement in survival of OCSCC and to determine factors associated with survival in the United States using a large administrative database. METHODS: Retrospective cohort study of 13,655 patients with OCSCC in the National Cancer Database diagnosed during time periods 1998-2003 and 2004-2006. Statistical methods included chi-square and Cox regression. RESULTS: Patients with early (Stages I and II) and late stage (Stages III and IV) disease had improvements of 36.2% and 16.0% in three-year overall survival, respectively. Receipt of adjuvant chemoradiation increased from 8.3% to 36.4% for late stage disease, while receipt of adjuvant therapy in early stage disease remained stable. Patients with early stage disease increased from 64.1% for years 1998-2003 to 67.4% during 2004-2006 (p<.001). Being diagnosed between 2004 and 2006 was associated with decreased mortality in early and late stage disease (HR 0.67 and 0.87, p<.001, respectively). Other treatment factors associated with improved survival for patients of all stages included treatment in a high-volume center (HR 0.91, p=.002) and undergoing neck dissection (HR 0.90, p=.001). CONCLUSIONS: Three-year overall survival has increased dramatically for OCSCC patients. Advanced stage patients have been increasingly treated with chemoradiotherapy, while treatment of early stage patients has remained relatively unchanged. While other factors such as negative surgical margins and undergoing neck dissection may be partly responsible for improvements in early stage patients, further study is needed to understand the observed survival improvements. PMID- 26553390 TI - Cause-specific excess mortality in patients treated for cancer of the oral cavity and oropharynx: A population-based study. AB - PURPOSE: To assess cause-specific mortality in a large population-based cohort of 14,393 patients treated for squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP) in The Netherlands between 1989 and 2006. PATIENTS AND METHODS: Causes of death were obtained for 94.7% of 9620 patients who had died up to January 1, 2009. We assessed standardized mortality ratios (SMR) and absolute excess mortality (AEM), comparing observed cause-specific mortality with expected mortality for our cohort based on general population mortality rates. RESULTS: Median survival was 3.9 years. Overall, the study population experienced a 6-fold higher (95% Confidence Interval (95% CI) 5.9-6.1) mortality risk compared with the general population. After three years, 41% of OP and 29% of OC patients had died due to cancer of the oral cavity and pharynx. Additionally, OC and OP patients experienced high excess mortality from esophageal (SMR 10.6 and 17.9) and lung cancer (SMR 4.6 and 6.3). With regard to non-cancer deaths, the highest AEMs were due to diseases of the circulatory system, with OC patients experiencing an AEM of 11.3 per 10,000 person-years for ischemic heart disease. OP patients experienced excess mortality due to pneumonia (AEM 22.1 per 10,000 person-years). The risk of death due to diseases of the digestive system was for OP and OC patients where about equal (AEM 28.7 and 23.80, respectively). The SMR for death due to pneumonia was more than two times higher (4.4 vs. 1.7) for OP patients than for OC patients (P<0.001). From 15 years after diagnosis, second tumors located outside the head and neck region accounted for most of the excess mortality. CONCLUSIONS: Excess mortality in OC and OP patients appears to be dominated by effects of heavy tobacco and alcohol use with high AEM due to second tumors, respiratory, cardiovascular and gastrointestinal diseases. Patients with OP experienced more than two times higher risk of death due to pneumonia than OC patients. Therefore, awareness of this potential complication should be raised along with development of prevention strategies. PMID- 26553392 TI - The origin of Korotkoff sounds and the accuracy of auscultatory blood pressure measurements. AB - This study explores the hypothesis that the sharper, high frequency Korotkoff sounds come from resonant motion of the arterial wall, which begins after the artery transitions from a buckled state to an expanding state. The motions of one mass, two nonlinear springs, and one damper, driven by transmural pressure under the cuff, are used to model and compute the Korotkoff sounds according to principles of classical Newtonian physics. The natural resonance of this spring mass-damper system provides a concise, yet rigorous, explanation for the origin of Korotkoff sounds. Fundamentally, wall stretching in expansion requires more force than wall bending in buckling. At cuff pressures between systolic and diastolic arterial pressure, audible vibrations (> 40 Hz) occur during early expansion of the artery wall beyond its zero pressure radius after the outward moving mass of tissue experiences sudden deceleration, caused by the discontinuity in stiffness between bucked and expanded states. The idealized spring-mass-damper model faithfully reproduces the time-domain waveforms of actual Korotkoff sounds in humans. Appearance of arterial sounds occurs at or just above the level of systolic pressure. Disappearance of arterial sounds occurs at or just above the level of diastolic pressure. Muffling of the sounds is explained by increased resistance of the artery to collapse, caused by downstream venous engorgement. A simple analytical model can define the physical origin of Korotkoff sounds, suggesting improved mechanical or electronic filters for their selective detection and confirming the disappearance of the Korotkoff sounds as the optimal diastolic end point. PMID- 26553393 TI - Precrystalline Aggregates Enable Control over Organic Crystallization in Solution. AB - Understanding and controlling organic crystallization in solution is a long standing challenge. Herein, we show that crystallization of an aromatic amphiphile based on perylene diimide in aqueous media involves initially formed amorphous spherical aggregates that evolve into the crystalline phase. The initial appearance of the crystalline order is always confined to the spherical aggregates that are precursors for crystalline evolution. The change in the solvation of the prenucleation phase drives the crystallization process towards crystals that exhibit very different structure and photofunction. The initial molecular structure and subsequent crystal evolution can be regulated by tuning the hydrophobicity at various stages of crystallization, affording dissimilar crystalline products or hindering crystallization. Thus, the key role of the precrystalline states in organic crystal evolution enables a new strategy to control crystallization by precrystalline state manipulation. PMID- 26553391 TI - Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants. AB - The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results demonstrate that local delivery of resveratrol can provide an additive advantage by providing a consistent reduction in the tissue response. PMID- 26553394 TI - CoPt/CeO2 catalysts for the growth of narrow diameter semiconducting single walled carbon nanotubes. AB - For the application of single-walled carbon nanotubes (SWNTs) in nanoelectronic devices, effective techniques for the growth of semiconducting SWNTs (s-SWNTs) with a specific diameter are still a great challenge. Herein, we report a facile strategy for the selective growth of narrow diameter distributed s-SWNTs using CoPt/CeO2 catalysts. The addition of Pt into a Co catalyst dramatically reduces the diameter distributions and even the chirality distributions of the as-grown SWNTs. Oxygen vacancies that are provided by mesoporous CeO2 are responsible for creating an oxidative environment to in situ etch metallic SWNTs (m-SWNTs). Atomic force microscope (AFM) and Raman spectroscopy characterizations indicate a narrow diameter distribution of 1.32 +/- 0.03 nm and the selective growth of s SWNTs to 93%, respectively. In addition, electronic transport measurements also confirm that the Ion/Ioff ratio is mainly in the order of ~10(3). This work provides an effective strategy for the facile fabrication of narrow diameter distributed s-SWNTs, which will be beneficial to fundamental research and the broad application of SWNTs for future nanoelectronics. PMID- 26553395 TI - Chemotherapy in pregnancy. AB - Cancer diagnosed during pregnancy is uncommon, complicating between 0.02% and 0.1% of all pregnancies. Nonetheless, due to increasing age of childbearing, the incidence of cancer during pregnancy is likely to increase due to higher incidence of several age-dependent malignancies. The most common malignancies include breast cancer, cervical cancer, malignant melanoma and lymphoma. One of the key challenges in the management of cancer in pregnancy is treating the women with standard chemotherapy regimen, without compromising the safety of the developing foetus. Exposure of chemotherapy in the first trimester is associated with an increased risk of major birth defects, whereas use in the second and third trimesters is associated with intrauterine growth restriction, low birthweight and stillbirth. In this article, we review available data regarding the use of chemotherapeutic agents in pregnancy, and we summarise the neonatal outcomes, including malformations, perinatal complications and long-term follow up. In addition, the management plan during pregnancy is also discussed. PMID- 26553396 TI - Acquired arteriovenous fistula without penetrating trauma. PMID- 26553397 TI - Impact of beta thalassemia on maxillary sinuses and sino-nasal passages: A case control study. AB - OBJECTIVES: Skeletal changes among beta (beta) thalassemia children are well documented, but without available data regarding sino-nasal passages alterations. The authors investigated the maxillary sinuses and sino-nasal passages changes in beta-thalassemia children and correlated such changes with the amount of transfused red cells and the erythroid marrow activity. METHODS: Clinical analyses including otorhinolaryngical examination (ORL) were obtained in twenty beta-thalassemia children and 20 matched healthy controls. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR) levels and bone mineral density of the lumbar spine (BMD ls) were assayed. The two groups were analyzed for the CT image parameters: bone thickness, anterior and posterior choanae diameters, extramedullary hematopoiesis and chronic rhinosinusitis (CRS) RESULTS: Nasal congestion/obstruction was identified in 14 (70%) children. Eight patients (40%) had criteria of chronic rhinosinusitis. In comparison with the normal controls, the increase in the roof, floor, medial, anterior, lateral and posterior maxillary bony walls thickness was significantly higher (1.26, 2.46, 2.6, 2.9, 3.23 and 5.34-folds, respectively). The mean posterior choanae horizontal, vertical diameters and their surface area were significantly reduced in the patients compared to the controls. The mean anterior maxillary wall bone thickness directly correlated with sTfR (P=0.047) while that of the posterior wall correlated inversely with Hb level (P=0.013). The mean vertical posterior choanae diameter had positive correlation with the amount of transfused red cells (P=0.001) and negative correlation with sTfR (P=0.001). The Hounsfield unit of maxillary sinus wall had direct relation with BMDls (P=0.003) CONCLUSIONS: Thalassemia children are at risk of different folds increase of maxillary sinuses walls thicknesses utmost at posterior and lateral walls. Other sino-nasal morbidities include diminished posterior choanal diameter, nasal obstruction and CRS. Certain morbidities had relations to the erythroid marrow activity and the transfusion adequacy. PMID- 26553398 TI - A high-fat diet is associated with otitis media with effusion. AB - OBJECTIVE: An association between obesity and otitis media with effusion (OME) has been previously reported. The aim of this study was to evaluate the association between dietary intake and OME when adjusting obesity. METHODS: We analyzed the differences in dietary intake between children with/without OME who were 4 through 13 years of age using data from a large population-based survey - the Korea National Health and Nutrition Examination Survey - from 2008 through 2012. Data from 4359 participants were analyzed using simple and multiple logistic regression analyses with complex sampling. RESULTS: The BMI category, the proportion of total calorie intake, protein intake, water intake, and Na intake (intake/recommendation), and the distribution of carbohydrate intake were not associated with OME. The distribution of fat intake was associated with OME (each 10% increase of fat calories/total calories: unadjusted odds ratio [OR]=1.331, 95% confidence interval [CI]=1.016-1.744, P=0.038; age- and sex adjusted OR=1.359, 95% CI=1.028-1.797, P=0.031; adjusted for age, sex and other factors OR=1.392, 95% CI=1.054-1.839, P=0.020). Based on BMI subgroup analysis, the distribution of fat intake was associated with OME in the healthy weight group (each 10% increase of fat calories/total calories: unadjusted OR=1.393, 95% CI=1.017-1.909, P=0.039; adjusted OR=1.470, 95% CI=1.051-2.055, P=0.024) but not in the obese group. CONCLUSIONS: A high-fat diet was associated with OME and may represent a confounding factor between obesity and OME. PMID- 26553399 TI - Two novel compound heterozygous families with a trimutation in the GJB2 gene causing sensorineural hearing loss. AB - BACKGROUND: Sensorineural hearing loss (SNHL) is a genetically heterogeneous disease. GJB2 gene mutations seem to be the most frequent cause of hereditary hearing impairment in several populations. There is variability in the mutations in the GJB2 gene worldwide; this remarks the influence of ethnic background in SNHL. OBJECTIVE: To describe the presence of two trimutations in the GJB2 gene in two Mexican families with hereditary SNHL. MATERIALS AND METHODS: Two unrelated Mexican families with prelingual SNHL were included in the study. Analysis of the GJB2 gene through PCR and DNA direct sequencing analysis was performed in all members of the families and in 100 normal controls. RESULTS: Affected member of the family 1 showed the trimutation p.S19R/p.R32S/p.E47*, whereas affected members of the family 2 showed the trimutation p.F31I/p.W44*/p.V84M. Parents of both families were heterozygous with normal audition. CONCLUSION: We found a novel mutation in the GJB2 gene and two trimutations with SNHL not previously reported. This remarks the complexity in the pattern of mutations in the GJB2 gene in SNHL and enriches the spectrum of the type of molecular defects in the GJB2 gene. PMID- 26553401 TI - Response to the Letter to the Editor regarding "Tympanic membrane perforation in children: Endoscopic type I tympanoplasty, a newly technique, is it worthwhile?" by Nassif et al. [Int. J. Pediatr. Otorhinolaryngol. 2015 (79) (11) 1860-1864]. PMID- 26553400 TI - Health-related quality of life among children with adenoid hypertrophy in Xi'an, China. AB - OBJECTIVE: The aim of this study was to investigate the health-related quality of life (HRQOL) in 5-7-year-old children diagnosed with adenoid hypertrophy and the impact of adenoid hypertrophy on affected families. METHODS: This is a cross sectional case-control study evaluating 5-7-year-old children with adenoid hypertrophy (n=195), 5-7-year-old healthy children (n=156), and associated caregivers (parents and/or grandparents). A Chinese version of the PedsQLTM 4.0 Generic Core Scale was used to assess childhood HRQOL, and a Chinese version of the Family Impact Module (FIM) was used to assess the impact of adenoid hypertrophy on family members. HRQOL scores were compared between the children with adenoid hypertrophy and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, and caregiver's HRQOL as independent variables were referenced to determine the factors that may influence HRQOL in children with adenoid hypertrophy. RESULTS: Children with adenoid hypertrophy showed significantly lower physical, emotional, social, and school functioning scores than healthy children (p<0.001 in all these dimensions). Caregivers for children with adenoid hypertrophy also scored significantly lower than caregivers for healthy children on physical, emotional, social, cognitive, and communication functioning (p<0.001 in all these dimensions). Caregivers for adenoid hypertrophy-affected children also exhibited significantly higher levels of worry than healthy children (p<0.001). Multivariate analyses demonstrated that children's age, children's relation with caregivers, caregiver's educational level, caregiver's own HRQOL, and the size of adenoid may all influence the HRQOL in children with adenoid hypertrophy (p<0.05). CONCLUSIONS: The current data suggested that adenoid hypertrophy were associated with lower HRQOL in both children and their caregivers, and may negatively influence family functioning. In addition, caregivers' social characteristics may also significantly affect the HRQOL in children with adenoid hypertrophy. PMID- 26553402 TI - A Multi-Objective Genetic Algorithm for Outlier Removal. AB - Quantitative structure activity relationship (QSAR) or quantitative structure property relationship (QSPR) models are developed to correlate activities for sets of compounds with their structure-derived descriptors by means of mathematical models. The presence of outliers, namely, compounds that differ in some respect from the rest of the data set, compromise the ability of statistical methods to derive QSAR models with good prediction statistics. Hence, outliers should be removed from data sets prior to model derivation. Here we present a new multi-objective genetic algorithm for the identification and removal of outliers based on the k nearest neighbors (kNN) method. The algorithm was used to remove outliers from three different data sets of pharmaceutical interest (logBBB, factor 7 inhibitors, and dihydrofolate reductase inhibitors), and its performances were compared with those of five other methods for outlier removal. The results suggest that the new algorithm provides filtered data sets that (1) better maintain the internal diversity of the parent data sets and (2) give rise to QSAR models with much better prediction statistics. Equally good filtered data sets in terms of these metrics were obtained when another objective function was added to the algorithm (termed "preservation"), forcing it to remove certain compounds with low probability only. This option is highly useful when specific compounds should be preferably kept in the final data set either because they have favorable activities or because they represent interesting molecular scaffolds. We expect this new algorithm to be useful in future QSAR applications. PMID- 26553403 TI - Copper surfaces are associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit. AB - BACKGROUND: Health care-associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper's inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit. METHODS: A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a 249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3 frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8 outfitted normally and 8 outfitted with antimicrobial copper. RESULTS: Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8 study rooms was found to suppress the microbial burden recovered from objects assessed in control rooms by log10 of 1.863 (73%). CONCLUSION: Copper surfaces warrant serious consideration when contemplating the introduction of no-touch disinfection technologies for reducing burden to limit acquisition of HAIs. PMID- 26553404 TI - Results of a Veterans Affairs employee education program on antimicrobial stewardship for older adults. AB - We describe a course in the Veterans Affairs (VA) Employee Education System designed to engage nursing staff working in VA long-term care facilities as partners in antimicrobial stewardship. We found that the course addressed an important knowledge gap. Our outcomes suggest opportunities to engage nursing staff in advancing antimicrobial stewardship, particularly in the long-term care setting. PMID- 26553405 TI - Multifunctional Mesoporous Silica Nanoparticles Based on Charge-Reversal Plug Gate Nanovalves and Acid-Decomposable ZnO Quantum Dots for Intracellular Drug Delivery. AB - A novel type of pH-responsive multifunctional mesoporous silica nanoparticle (MSN) was developed for cancerous cells drug delivery and synergistic therapy of tumor. MSNs were covered with a kind of cell-penetrating peptide, deca-lysine sequence (K10), to enhance their escape from the endosomes. After K10's primary amines were reacted with citraconic anhydride to form acid-labile beta-carboxylic amides, zinc oxide (ZnO) quantum dots (QDs) were introduced to cap MSNs via electrostatic interaction. The obtained ZnO@MSN drug-delivery system (DDS) achieves "zero-premature" drug release under a physiological environment. However, once the DDS is transferred to the cancerous cells' acidic endosome, ZnO QDs would rapidly dissolve and the acid-labile amides on the side chain of K10 would hydrolyze to regenerate primary amines, resulting in the uncapping of MSNs and exposure of the cell-penetrating peptide K10. The regenerated K10 could help the DDS escape from the endosome and efficiently release the loaded drugs inside the cells. At the meantime, because of the cytotoxicity of ZnO QDs at their destination, the ZnO@MSN DDS may achieve a synergistic antitumor effect to improve the therapeutic index. PMID- 26553407 TI - Paraplegia Due to Spinal Cord Infarction After Coronary Artery Bypass Graft Surgery. AB - Paraplegia is an extremely rare complication after coronary artery bypass grafting (CABG) and the underlying mechanisms remain poorly understood. We report a patient who developed paraplegia after CABG and review the literature on spinal cord ischemia following CABG surgery. PMID- 26553406 TI - 3D genome organization in health and disease: emerging opportunities in cancer translational medicine. AB - Organizing the DNA to fit inside a spatially constrained nucleus is a challenging problem that has attracted the attention of scientists across all disciplines of science. Increasing evidence has demonstrated the importance of genome geometry in several cellular contexts that affect human health. Among several approaches, the application of sequencing technologies has substantially increased our understanding of this intricate organization, also known as chromatin interactions. These structures are involved in transcriptional control of gene expression by connecting distal regulatory elements with their target genes and regulating co-transcriptional splicing. In addition, chromatin interactions play pivotal roles in the organization of the genome, the formation of structural variants, recombination, DNA replication and cell division. Mutations in factors that regulate chromatin interactions lead to the development of pathological conditions, for example, cancer. In this review, we discuss key findings that have shed light on the importance of these structures in the context of cancers, and highlight the applicability of chromatin interactions as potential biomarkers in molecular medicine as well as therapeutic implications of chromatin interactions. PMID- 26553408 TI - Acute Kidney Injury After Surgical AVR and Long-Term Risk of Death and End Stage Renal Disease. PMID- 26553409 TI - Reply. PMID- 26553410 TI - Subgroups in cephalosporin allergy, making a patient-tailored approach redundant? PMID- 26553411 TI - Layers: A molecular surface peeling algorithm and its applications to analyze protein structures. AB - We present an algorithm 'Layers' to peel the atoms of proteins as layers. Using Layers we show an efficient way to transform protein structures into 2D pattern, named residue transition pattern (RTP), which is independent of molecular orientations. RTP explains the folding patterns of proteins and hence identification of similarity between proteins is simple and reliable using RTP than with the standard sequence or structure based methods. Moreover, Layers generates a fine-tunable coarse model for the molecular surface by using non random sampling. The coarse model can be used for shape comparison, protein recognition and ligand design. Additionally, Layers can be used to develop biased initial configuration of molecules for protein folding simulations. We have developed a random forest classifier to predict the RTP of a given polypeptide sequence. Layers is a standalone application; however, it can be merged with other applications to reduce the computational load when working with large datasets of protein structures. Layers is available freely at http://www.csb.iitkgp.ernet.in/applications/mol_layers/main. PMID- 26553412 TI - Prognostic value of skin lesions in sarcoidosis: clinical and histopathological clues. AB - BACKGROUND: Although tremendous advances have been made, a significant gap exists between the vast knowledge accumulated concerning sarcoidosis in recent years and our understanding of this disease. OBJECTIVE: Describe the main clinical and histopathological findings associated with cutaneous sarcoidosis and to investigate the relationship of these skin lesions with systemic involvement. METHODS: A retrospective review of 41 patients who were diagnosed with cutaneous sarcoidosis was done. RESULTS: The study included 34 females and 7 males. Systemic disease occurred frequently in patients with lupus pernio and nodulo plaque type lesions. Systemic symptoms were observed more commonly in patients with raised serum ACE levels (84.6% vs. 40%; p<0.05). Our study also indicated that patients with skin lesions that were associated with systemic symptoms had a more chronic form of the disease than patients with only cutaneous lesions (91.6% vs. 29.4%; p<0.001). Additionally, complete resolution of cutaneous lesions was observed more frequently in patients with no associated systemic symptoms (66.6% vs. 23.5%; p<0.05). Interestingly, we found that patients with a moderate/severe granulomatous infiltrate in their biopsies had a more severe clinical presentation during the course of the disease, with a more generalized skin involvement (65.6% vs. 30%) as well as a more chronic course of the disease (56.3% vs. 30%). Another interesting histopathological finding observed was the presence of a grenz zone in 20 cases (47.6%). CONCLUSION: A correct and methodical clinicopathological correlation is important for our clinical practice because it can give us useful clues to the diagnosis and prognosis of this disease. PMID- 26553413 TI - Correction of Retrograde Ejaculation in Patients with Diabetes Mellitus Using Endourethral Collagen Injection: Preliminary Results. AB - INTRODUCTION: Diabetic neuropathy secondary to diabetes mellitus type 1 (DM1) is responsible for retrograde ejaculation (RE) in 5-18% of cases. Medical treatment of RE is based either on increasing the sympathetic tone of the bladder or on decreasing the parasympathetic activity. However, the onset of side effects and the lack of response should be considered. AIMS: The aim of this study was to analyze long-term outcome of endourethral injection of volume-forming material (VFM) of collagen type 2 into bladder neck submucosa in patients with RE secondary to DM1. METHODS: Twenty-four patients with complete RE refractory to imipramine and DM1 were included in the study. Patients were single-blinded randomized according to a computer-generated random sequence with a 1:1 ratio in two treatment groups, namely group A (endourethral collage type 2 injection) and group B (endourethral saline water injection). New technique includes an endoscopic injection of VFM such as collagen (Correcting MIT(r), Ltd. minimally invasive technologies, Moscow, Russia) into bladder neck submucosa. Primary endpoint of the study was the reduction of semen antegrade volume (mL). Secondary endpoints were considered as the changes of antegrade count (millions/mL), antegrade total motility (%), antegrade progressive motility (%), State-Trait Anxiety Inventory, Beck Depression Questionnaire and International Index of Erectile Function (IIEF-5). Pregnancy rate was calculated in each group. RESULTS: Twenty-three patients completed the study. In group A, significant differences from baseline to 12 months were observed relative to antegrade volume (mL) (mean difference: 0.71, P < 0.05), antegrade count (millions/mL) (mean difference: 45.6, P < 0.05), antegrade total motility (%) (mean difference: 15.4, P < 0.05) and antegrade progressive motility (%) (mean difference: 8.4, P < 0.05). In group A, we observed significant differences in terms State-Trait Anxiety Inventory (mean difference: -20.5, P < 0.05) and Beck Depression Inventory (mean difference: -8.4, P < 0.05) with significant differences compared with group B. We observed significant improvements in group A vs. group B when considering primary and secondary endpoints of the study, but not for the IIEF-5. CONCLUSION: Correction of RE in DM1 patients could be achieved with endourethral injection of collagen type 2. PMID- 26553414 TI - Phase diagram of the layered oxide SnO: GW and electron-phonon studies. AB - First-principles calculations are performed to study the electronic properties and the electron-phonon interactions of the layered oxide semiconductor SnO. In addition to the high hole mobility that makes SnO a promising material in electronics, it has recently been reported that the semimetallic phase under pressure is superconducting. The superconducting Tc curve exhibits a dome-like feature under pressure and reaches the maximum of 1.4 K at p = 9.2 GPa. Both its crystal structure and the dome-like Tc curve are reminiscent of the Fe-based superconductor FeSe. Motivated by this observation, we investigate the electronic, phonon, and their interactions in SnO using first-principles schemes. GW approximation is adopted to correct the underestimated band gaps, including real and continuous band gaps in the semiconducting and semimetallic phases. The phase diagram showing the semiconductor-to-semimetal transition and the Tc curve has been successfully reproduced. Detailed analysis of the electron-phonon interactions demonstrate the importance of the out-of-plane motions of O atoms and the Sn-s lone pairs for the superconductivity to occur. Our method combining GW and e-ph calculations can be further extended to the study of other materials that undergo insulator-to-superconductor phase transition. PMID- 26553415 TI - Construction of photodynamic-effect immunofluorescence probes by a complex of quantum dots, immunoglobulin G and chlorin e6 and their application in HepG2 cell killing. AB - In this study, tri-functional immunofluorescent probes (Ce6-IgG-QDs) based on covalent combinations of quantum dots (QDs), immunoglobulin G (IgG) and chlorin e6 (Ce6) were developed and their photodynamic ability to induce the death of cancer cells was demonstrated. Strategically, one type of second-generation photosensitizer, Ce6, was first coupled with anti-IgG antibody using the EDC/NHS cross-linking method to construct the photosensitive immunoconjugate Ce6-IgG. Then, a complex of Ce6-IgG-QDs immunofluorescent probes was obtained in succession by covalently coupling Ce6-IgG to water soluble CdTe QDs. The as manufactured Ce6-IgG-QDs maintained the bio-activities of both the antigen antibody-based tumour targeting effects of IgG and the photodynamic-related anticancer activities of Ce6. By way of polyclonal antibody interaction with rabbit anti-human epidermal growth factor receptor (anti-EGFR antibody, N terminus), Ce6-IgG-QDs were labelled indirectly onto the surface of human hepatocarcinoma (HepG2) cells in cell recognition and killing experiments. The results indicated that the Ce6-IgG-QDs probes have excellent tumour cell selectivity and higher photosensitivity in photodynamic therapy (PDT) compared with Ce6 alone, due to their antibody-based specific recognition and location of HepG2 cells and the photodynamic effects of Ce6 killed cells based on efficient fluorescence resonance energy transfer between QDs and Ce6. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26553416 TI - Dental stem cells: a future asset of ocular cell therapy. AB - Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine. PMID- 26553417 TI - Primary biliary cirrhosis: Renaming primary biliary cirrhosis-clarity or confusion? PMID- 26553418 TI - Hepatocellular carcinoma: Ectopic lymphoid structures promote carcinogenesis in the liver. PMID- 26553419 TI - Stress lowers the detection threshold for foul-smelling 2-mercaptoethanol. AB - Previous studies have reported enhanced vigilance for threat-related information in response to acute stress. While it is known that acute stress modulates sensory systems in humans, its impact on olfaction and the olfactory detection of potential threats is less clear. Two psychophysical experiments examined, if acute stress lowers the detection threshold for foul-smelling 2-mercaptoethanol. Participants in Experiment 1 (N = 30) and Experiment 2 (N = 32) were randomly allocated to a control group or a stress group. Participants in the stress group underwent a purely psychosocial stressor (public mental arithmetic) in Experiment 1 and a stressor that combined a physically demanding task with social-evaluative threat in Experiment 2 (socially evaluated cold-pressor test). In both experiments, olfactory detection thresholds were repeatedly assessed by means of dynamic dilution olfactometry. Each threshold measurement consisted of three trials conducted using an ascending method of limits. Participants in the stress groups showed the expected changes in heart rate, salivary cortisol, and mood measures in response to stress. About 20 min after the stressor, participants in the stress groups could detect 2-mercaptoethanol at a lower concentration than participants in the corresponding control groups. Our results show that acute stress lowers the detection threshold for a malodor. PMID- 26553420 TI - Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. AB - The rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin's ability to suppress production of key MRSA toxins (alpha-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. PMID- 26553422 TI - Implementing Indigenous community control in health care: lessons from Canada. AB - Objective Over past decades, Australian and Canadian Indigenous primary healthcare policies have focused on supporting community controlled Indigenous health organisations. After more than 20 years of sustained effort, over 89% of eligible communities in Canada are currently engaged in the planning, management and provision of community controlled health services. In Australia, policy commitment to community control has also been in place for more than 25 years, but implementation has been complicated by unrealistic timelines, underdeveloped change management processes, inflexible funding agreements and distrust. This paper discusses the lessons from the Canadian experience to inform the continuing efforts to achieve the implementation of community control in Australia. Methods We reviewed Canadian policy and evaluation grey literature documents, and assessed lessons and recommendations for relevance to the Australian context. Results Our analysis yielded three broad lessons. First, implementing community control takes time. It took Canada 20 years to achieve 89% implementation. To succeed, Australia will need to make a firm long term commitment to this objective. Second, implementing community control is complex. Communities require adequate resources to support change management. And third, accountability frameworks must be tailored to the Indigenous primary health care context to be meaningful. Conclusions We conclude that although the Canadian experience is based on a different context, the processes and tools created to implement community control in Canada can help inform the Australian context. What is known about the topic? Although Australia has promoted Indigenous control over primary healthcare (PHC) services, implementation remains incomplete. Enduring barriers to the transfer of PHC services to community control have not been addressed in the largely sporadic attention to this challenge to date, despite significant recent efforts in some jurisdictions. What does this paper add? The Canadian experience indicates that transferring PHC from government to community ownership requires sustained commitment, adequate resourcing of the change process and the development of a meaningful accountability framework tailored to the sector. What are the implications for practitioners? Policy makers in Australia will need to attend to reform in contractual arrangements (towards pooled or bundled funding), adopt a long-term vision for transfer and find ways to harmonise the roles of federal and state governments. The arrangements achieved in some communities in the Australian Coordinated Care Trials (and still in place) provide a model. PMID- 26553421 TI - Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY. AB - PURPOSE: To evaluate the long-term safety of Pegvisomant (PEG) in the Spanish cohort of ACROSTUDY. METHODS: As of July 2013, 199 Spanish patients were included in ACROSTUDY, a global non interventional safety PEG surveillance study. Patients were observed for safety, biochemical outcome and magnetic resonance imaging evaluations. RESULTS: PEG was administered during an average period of 6.7 +/- 2.1 years and a mean daily dose of 15.5 +/- 7.5 mg. 48.2% of patients received PEG monotherapy. 90.9% of patients had received other medical treatment before PEG start. 195 adverse events (AEs) were reported in 88 patients (44.2%), and serious AEs were described in 31 patients (15.6%). There were no cases of liver tests >10 ULN, or permanent liver damage. Tumor size changes were locally reported in 61 cases (33.5%), with increases observed in 11 patients (6%). In acromegalic patients with diabetes mellitus a decrease in fasting serum glucose value was reported, reaching statistical significance after 1 and 4 years of treatment (-24.6 and -25.9 mg/dl, p = 0.04). After 60 months, normal or lower limit of normal (LLN) IGF-I levels were found in 67.9% of patients. 85.5% of patients showed an IGF-I normal or =3 positive LNs who require axillary lymph node dissection (ALND). We sought to identify the total number of positive LNs in women presenting with cT1-2N0 breast carcinoma with a positive preoperative LN biopsy to evaluate the potential for overtreatment when ALND is performed on the basis of a positive needle biopsy in patients who otherwise meet ACOSOG Z0011 eligibility criteria. METHODS: Patients with cT1-2N0 breast cancer by physical examination with a positive preoperative LN biopsy were identified from a prospective institutional database. Clinicopathologic characteristics and axillary imaging results were compared between women with 1 to 2 total positive LNs and >=3 total positive LNs. RESULTS: Between May 2006 and December 2013, a total of 141 women with cT1-2N0 breast cancer had abnormal axillary imaging and a preoperative positive LN biopsy (median patient age 51 years, median tumor size 2.4 cm, 86 % ductal histology, 79 % estrogen receptor positive). Sixty-six women (47 %) had 1 to 2 total positive LNs, and 75 (53 %) had >=3 total positive LNs. Women with >=3 total positive LNs had larger tumors (2.4 vs. 2.2 cm, p = 0.03), fewer tumors with ductal histology (79 vs. 94 %, p = 0.01), more lymphovascular invasion (80 vs. 61 %, p = 0.01), and higher median body mass index (29.2 vs. 27.1 kg/m(2), p = 0.04). Having >1 abnormal LN on axillary imaging was significantly associated with having >=3 total positive LNs at final pathology (68 vs. 43 %, p = 0.003). CONCLUSIONS: Axillary imaging with preoperative LN biopsy does not accurately discriminate low- versus high-volume nodal disease in clinically node-negative patients. PMID- 26553440 TI - Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). AB - BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous drug distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial drug distribution pattern of PIPAC has not been investigated in detail. METHODS: Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 degrees C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 +/ 79 um) compared with the side wall (C: 77 +/- 18 um; p < 0.01) and the top of the box (D: 65 +/- 17 um; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 +/- 19 um; p < 0.001). CONCLUSIONS: The study data suggest that the spatial drug distribution pattern of ex vivo PIPAC is heterogeneous. PMID- 26553438 TI - Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer. AB - Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 * 10( 7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 * 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 * 10(-7) and OR = 1.09, P = 7.4 * 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 * 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 * 10(-6)). We found an excess of rare, damaging variants in base-excision (P = 2.4 * 10(-4)) and DNA mismatch repair genes (P = 6.1 * 10(-4)) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC. PMID- 26553442 TI - Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma. AB - BACKGROUND: Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). METHODS: Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). RESULTS: Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034). CONCLUSIONS: Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited. PMID- 26553443 TI - "Deeply disappointing" public health cuts will increase demand on NHS, says expert. PMID- 26553441 TI - Factors Associated with Short-Term Mortality After Surgical Oncologic Emergencies. AB - BACKGROUND: The clinical outcome of patients with oncologic emergencies is often poor and mortality is high. It is important to determine which patients may benefit from invasive treatment, and for whom conservative treatment and/or palliative care would be appropriate. In this study, prognostic factors for clinical outcome are identified in order to facilitate the decision-making process for patients with surgical oncologic emergencies. METHODS: This was a prospective registration study for patients over 18 years of age, who were consulted for surgical oncologic emergencies between November 2013 and April 2014. Multiple variables were registered upon emergency consultation, and the follow-up period was 90 days. Multivariate logistic regression analysis was performed to identify factors associated with 30- and 90-day mortality. RESULTS: During the study period, 207 patients experienced surgical oncologic emergencies 101 (48.8 %) men and 106 (51.2 %) women, with a median age of 64 years (range 19 92). The 30-day mortality was 12.6 % and 90-day mortality was 21.7 %. Factors significantly associated with 30-day mortality were palliative intent of cancer treatment prior to emergency consultation (p = 0.006), Eastern Cooperative Oncology Group performance score (ECOG-PS) >0 (p for trend: p = 0.03), and raised lactate dehydrogenase (LDH) (p < 0.001). Additional factors associated with 90 day mortality were low handgrip strength (HGS) (p = 0.01) and low albumin (p = 0.002). CONCLUSIONS: Defining the intent of prior cancer treatment and the ECOG PS are of prognostic value when deciding on treatment for patients with surgical oncologic emergencies. Additional measurements of HGS, LDH, and albumin levels can serve as objective parameters to support the clinical assessment of individual prognosis. PMID- 26553444 TI - Testing for Basins of Wada. AB - Nonlinear systems often give rise to fractal boundaries in phase space, hindering predictability. When a single boundary separates three or more different basins of attraction, we say that the set of basins has the Wada property and initial conditions near that boundary are even more unpredictable. Many physical systems of interest with this topological property appear in the literature. However, so far the only approach to study Wada basins has been restricted to two-dimensional phase spaces. Here we report a simple algorithm whose purpose is to look for the Wada property in a given dynamical system. Another benefit of this procedure is the possibility to classify and study intermediate situations known as partially Wada boundaries. PMID- 26553445 TI - John Edward Salvaggio, MD, MACP, 1933-1999. PMID- 26553446 TI - Developing a risk stratification model for predicting future health care use in asthmatic children. AB - BACKGROUND: Previous studies have stratified pediatric asthma patients for risk of future exacerbation and/or health care use, but most incorporate multiple clinical parameters. OBJECTIVE: To determine whether historical acute care visits (ACVs) alone could predict risk of future health care use. METHODS: Children seen for asthma in an outpatient visit during a 3-year period were identified. The number of ACVs in the 12 months before and after the outpatient visit was determined. Logistic regression models were used to determine the odds of a future ACV. Models were adjusted for age, sex, race, and insurance status. RESULTS: Of 28,047 outpatient visits, 21,099 (75.2%) had no historical ACVs. The probability of a future ACV increased from 30% with one historical ACV to 87% with 5 or more historical ACVs. Outpatient visits with one historical ACV had significantly higher odds of a future ACV compared with those with no historical ACVs (adjusted odds ratio [OR], 3.60; 95% confidence interval [CI], 3.14-4.12; P < .001). The OR increased with each additional historical ACV to an adjusted OR of 58.71 (95% CI, 24.34-141.61; P < .001) with 5 or more historical ACVs. Outpatient visits with 5 or more historical ACVs represented only 1.1% of the study sample but accounted for a higher mean number of future ACVs. CONCLUSION: The historical count of ACVs was predictive of future ACVs. A significant increase in the probability of future ACVs was observed with each additional historical visit, effectively stratifying risk by the historical visit count. Notably, a small group of patients accounted for a disproportionate number of future ACVs. PMID- 26553447 TI - ADAM33 and ADAM12 genetic polymorphisms and their expression in Egyptian children with asthma. AB - BACKGROUND: The ADAM family is involved in some pathologic processes, such as inflammation and asthma. OBJECTIVES: To assess the association between ADAM33 and ADAM12 single-nucleotide polymorphisms (SNPs) with asthma risk and severity and to investigate the effect of ADAM33 and ADAM12 polymorphisms on expression of these proteases in sputum. METHODS: Two SNPs of the ADAM33 gene, F+1 (rs511898) G/A and ST+4 (rs44707) A/C, and 2 SNPs of the ADAM12 gene, rs3740199 and rs1871054, were analyzed in 400 asthma cases and 200 controls aged 3 to 14 years using the polymerase chain reaction-restriction fragment length polymorphism method. Messenger RNA expression profile of ADAM33 and ADAM12 proteases in sputum from studied groups was determined by reverse transcription polymerase chain reaction. RESULTS: ADAM33 F+1 homozygous mutant genotype (AA) and ST+4 heterozygous and homozygous mutant genotype (AC and CC) and mutant alleles of both polymorphisms were significantly associated with asthma risk and severity in moderate and severe subgroups. Patients with the ADAM12 (rs3740199) CC genotype were at increased risk for moderate and severe asthma. Messenger RNA levels of ADAM12 were significantly increased in asthmatic children compared with controls, whereas we were not able to detect the expression of ADAM33 in the sputum of the groups studied. The ADAM12 expression was significantly higher in homozygous CC (variant type) compared with homozygous GG (wild type) of both ADAM12 rs3740199 and rs1871054 in the asthmatic group. CONCLUSION: Our analysis suggests a likely role for ADAM33 and ADAM12 in the development of asthma in Egyptian children. Furthermore, ADAM12 polymorphisms may affect ADAM12 expression in asthma. PMID- 26553448 TI - Safety of house dust mite sublingual immunotherapy standardized quality tablet in children allergic to house dust mites. AB - BACKGROUND: Sublingual immunotherapy (SLIT) tablets could be an important alternative to subcutaneous immunotherapy for house dust mite (HDM) allergy in children. OBJECTIVE: To characterize the safety, tolerability, and duration of local adverse events (AEs) of an HDM SLIT tablet (MK-8237; Merck, ALK Abello, and Torii) in North American children 12 to 17 years old with HDM allergic rhinitis with and without conjunctivitis and with or without asthma. METHODS: In this phase 1, multicenter, double-blinded, randomized trial (NCT01678807), children received placebo, HDM SLIT tablet 6 standardized quality (SQ) HDM, or 12 SQ-HDM once daily for 28 days. The primary end point was the proportion of subjects with treatment-emergent AEs receiving active treatment vs placebo. The secondary end point was the proportion of subjects who discontinued owing to AEs. RESULTS: In total 195 subjects were randomized. The 2 HDM SLIT tablet doses were well tolerated. No anaphylactic reactions, systemic allergic reactions, AEs requiring epinephrine, serious AEs, or local swellings in the mouth or throat assessed as severe were reported. The proportion of subjects with treatment-emergent AEs was 54% with 6 SQ-HDM and 57% with 12 SQ-HDM (nonsignificant vs 43% with placebo). Local AEs were the most commonly reported treatment-emergent AEs. On day 1, the median duration of individual local AEs ranged from 1 to 43 minutes. The proportion of subjects who discontinued owing to AEs was 0%, 6.2%, and 6.2%, and who experienced treatment-related AEs was 25%, 45%, and 52% for the placebo, 6 SQ HDM, and 12 SQ-HDM groups, respectively. CONCLUSION: The 6 and 12 SQ-HDM doses of the HDM SLIT tablet MK-8237 were well tolerated, and local AEs were of short duration. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01678807. PMID- 26553449 TI - Duodenal intussusception secondary to web presenting as recurrent pancreatitis in a 7-year-old girl. AB - Duodenal intussusception is a rare entity in children, with 32 cases reported in the English literature to our knowledge. Most reported cases are associated with endoluminal tubes or polyps, and the presenting symptoms are chronic and nonspecific. We report a case of duodenal intussusception in a 7-year-old girl secondary to a duodenal web and review the imaging findings. PMID- 26553450 TI - Policies for the vaccination of cats and dogs in New Zealand veterinary practices. AB - AIMS: To determine current practices and attitudes towards vaccination of dogs and cats of veterinarians in New Zealand; the methods used for informing clients on which vaccines to use, and the preferred site for vaccination of cats. METHODS: A postal questionnaire was sent to all 483 listed veterinary practices in New Zealand during February 2012. Some questions were specific to pet dogs, cats, or working farm dogs. Responses were categorised according to practice type and geographical region of the respondent. Factors associated with respondent recommendation of annual vaccination with modified live viral (MLV) vaccines were examined using logistic regression analysis. Vaccines that were considered to be essential for every animal were defined as core; those that may be recommended for animals whose location or lifestyle placed them at risk, were defined as non core. RESULTS: There were 204 useable returns, equivalent to a response rate of 42.2%, distributed across the country. Annual vaccination with MLV vaccines of dogs was recommended by 54/198 (27.3%) respondents, and of cats by 107/181 (59.1%) respondents. Factors associated with the recommendation of annual administration of MLV vaccines to dogs included being a companion animal practice, a desire for policies on vaccination to be left to individual clinics, and having one veterinarian in the practice. Administration of the final vaccination for puppies was recommended at >=14 weeks old by 55/185 (29.7%) respondents, and for kittens at >=13 weeks old by 42/183 (23%) respondents. Of respondents that administered MLV vaccines annually, 62/103 (60.2%) believed reducing the frequency of vaccination would reduce income, and 52/103 (50.5%) considered it would have a negative effect on animal health. Advice to enable clients to decide which non-core vaccines were administered was given by 181/199 (91%) respondents. Factors considered when recommending a vaccine included consideration of risk to individual patients (190/203; 93.6%), requirements of boarding kennels/catteries (165/203; 81.3%) and clinic vaccination policy (142/203; 70%). The preferred site for administering MLV vaccines to cats was the dorsal neck or inter-scapular region (137/198; 69.2%). Amongst respondents, 18 wanted disease surveillance information to allow for truly informed decisions to be made about vaccination. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians can now compare their own vaccination practices and attitudes with those of veterinarians nationally, and internationally. There is a need for national surveillance information and for continued education of the public and commercial kennel and cattery owners for optimal vaccination strategies to be developed. PMID- 26553451 TI - Contemporary approaches to basal cell carcinoma diagnosis and treatment. PMID- 26553452 TI - ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis. AB - Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis. PMID- 26553453 TI - Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists. AB - We examined if supplementing trained cyclists (32 +/- 2 year, 77.8 +/- 2.6 kg, and 7.4 +/- 1.2 year training) with 12 g/day (6 g/day L-Leucine, 2 g/day L Isoleucine and 4 g/day L-Valine) of either branched-chain amino acids (BCAAs, n = 9) or a maltodextrin placebo (PLA, n = 9) over a 10-week training season affected select body composition, performance, and/or immune variables. Before and after the 10-week study, the following was assessed: (1) 4-h fasting blood draws; (2) dual X-ray absorptiometry body composition; (3) Wingate peak power tests; and (4) 4 km time-trials. No group * time interactions existed for total lean mass (P = 0.27) or dual-leg lean mass (P = 0.96). A significant interaction existed for body mass-normalized relative peak power (19 % increase in the BCAA group pre- to post-study, P = 0.01), and relative mean power (4 % increase in the BCAA group pre- to post-study, P = 0.01). 4 km time-trial time to completion approached a significant interaction (P = 0.08), as the BCAA group improved in this measure by 11 % pre- to post-study, though this was not significant (P = 0.15). There was a tendency for the BCAA group to present a greater post-study serum BCAA: L Tryptophan ratio compared to the PLA group (P = 0.08). A significant interaction for neutrophil number existed (P = 0.04), as there was a significant 18 % increase within the PLA group from the pre- to post-study time point (P = 0.01). Chronic BCAA supplementation improves sprint performance variables in endurance cyclists. Additionally, given that BCAA supplementation blunted the neutrophil response to intense cycling training, BCAAs may benefit immune function during a prolonged cycling season. PMID- 26553454 TI - Effects of sodium ions on rat thyrocyte (FRTL-5 cells) swelling- and thyrotropin activated taurine efflux dependent on cAMP and Epac. AB - Cellular osmolyte release is important in preventing water accumulation and swelling. However, the signaling pathways that detect volume increase and activate solute efflux are still not fully understood. We investigated efflux activation of the osmolyte taurine which is actively accumulated in rat thyrocytes (FRTL-5). Efflux of accumulated [(3)H]taurine was stimulated by cellular swelling and thyrotropin (TSH). These effects were significantly diminished in cells having reduced TSH receptor concentrations. Phosphodiesterase inhibitors (IBMX, Rolipram) enhanced both responses. An analog of forskolin (FSK; 7-deacetyl-7-[O-(N-methylpiperazino)-gamma-butyryl] dihydrochloride) and an analog of cAMP, specific for activating exchange protein activated directly by cAMP (Epac; 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate, acetoxymethyl ester), significantly stimulated [(3)H]taurine efflux. A cAMP analog specific for activating protein kinase A (PKA; N6 benzoyladenosine-3',5'-cyclic monophosphate, acetoxymethyl ester) had no significant stimulatory effect on [(3)H]taurine efflux rate. The amiloride analog, 5-(N-ethyl-N-isopropyl)-amiloride, which inhibits a TSH-stimulated Na(+)/H(+) exchanger, enhanced (100 %) and ouabain inhibited (50 %) the TSH stimulated [(3)H]taurine efflux rate. The effect of FSK on efflux was strongly potentiated by Na(+)-free iso-osmotic conditions and by osmolality/cell volume that affected also the db-cAMP-stimulated efflux. The TSH receptors and downstream elements of the signaling pathway comprising adenylyl cyclase, cAMP and Epac appeared to mediate the hormone-induced signal for [(3)H]taurine efflux from FRTL-5 cells. With less evidence, the cell volume/osmolality-induced [(3)H]taurine efflux cascade appeared to share some of the hormone signaling elements and to modulate the hormone signaling pathway at two levels through cellular Na(+). PMID- 26553455 TI - Persistent organic pollutant levels and the importance of source proximity in Baltic and Svalbard breeding common eiders. AB - The distance to sources and the long-range transport potential of persistent organic pollutants (POPs) are important in understanding the impact of anthropogenic pollution on natural seabird populations. The present study documented blood concentrations of POPs in the Baltic Sea (Tvarminne, Finland) population of common eiders (Somateria mollissima) in 2009 and in 2011 and compared the concentrations with the presumably less exposed Arctic population in Svalbard (Kongsfjorden, Norway). The Baltic population had 26, 10, and 5 times greater concentrations of hexachlorocyclohexane, polychlorinated biphenyls, and p,p'-dichlorodiphenyldichloroethylene than the Svalbard population. Unexpectedly, concentrations of chlordanes were higher in Svalbard eiders, whereas concentrations of hexachlorobenzenes (HCBs) did not differ between the 2 populations. Although the similar HCB levels may partly be explained by the high transport potential of HCBs, unknown factors may have been more important than distance to sources and long-range transport potential for the chlordanes. One plausible explanation may be that the fasting-related redistribution of POPs from fat to blood was greater throughout the incubation in Arctic eiders, causing them to have higher blood levels of these POPs at the end of incubation. The blood concentrations of POPs in Baltic eiders were higher than documented in any other eider population and were comparable to levels in seabirds feeding at higher trophic positions in the food chain. Environ Toxicol Chem 2016;35:1526-1533. (c) 2015 SETAC. PMID- 26553456 TI - RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon RNA fusions in forward genetic cancer screens. AB - Forward genetic screens using Sleeping Beauty (SB)-mobilized T2/Onc transposons have been used to identify common insertion sites (CISs) associated with tumor formation. Recurrent sites of transposon insertion are commonly identified using ligation-mediated PCR (LM-PCR). Here, we use RNA sequencing (RNA-seq) data to directly identify transcriptional events mediated by T2/Onc. Surprisingly, the majority (~80%) of LM-PCR identified junction fragments do not lead to observable changes in RNA transcripts. However, in CIS regions, direct transcriptional effects of transposon insertions are observed. We developed an automated method to systematically identify T2/Onc-genome RNA fusion sequences in RNA-seq data. RNA fusion-based CISs were identified corresponding to both DNA-based CISs (Cdkn2a, Mycl1, Nf2, Pten, Sema6d, and Rere) and additional regions strongly associated with cancer that were not observed by LM-PCR (Myc, Akt1, Pth, Csf1r, Fgfr2, Wisp1, Map3k5, and Map4k3). In addition to calculating recurrent CISs, we also present complementary methods to identify potential driver events via determination of strongly supported fusions and fusions with large transcript level changes in the absence of multitumor recurrence. These methods independently identify CIS regions and also point to cancer-associated genes like Braf. We anticipate RNA-seq analyses of tumors from forward genetic screens will become an efficient tool to identify causal events. PMID- 26553457 TI - Tenosynovial giant cell tumour (pigmented villonodular synovitis-)-like changes in periprosthetic interface membranes. AB - Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF 1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis. PMID- 26553458 TI - Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin activity. AB - BACKGROUND: Antithrombin is one of the main natural coagulation system inhibitors. It is potentiated by heparin, and may be a key component of heparin response, particularly in infants aged <1 year. We sought to determine the impact of baseline antithrombin activity on response to heparin and thrombin generation during cardiopulmonary bypass (CPB). METHODS: Secondary analysis was performed using linear regression analyses, which combined patients from a trial of individualized versus weight-based heparin management for 90 infants aged <1 year undergoing cardiac surgery. RESULTS: Mean baseline antithrombin activity was 0.69 +/- 0.16 U/mL, and it was lower in neonates than in older infants (0.57 +/- 0.15 vs 0.77 +/- 0.12 U/mL; P < .001). Lower baseline antithrombin activity was associated with lower postheparin anti-Xa activity (EST [SE]: +0.47 (0.19) U/mL per 100 U/kg heparin; P = .01) and higher heparin doses during surgery (EST [SE]: +51 (17) U/kg per hour; P = .003). The administration of fresh frozen plasma attenuated the effect of low baseline antithrombin activity (interaction P value = .009). Patients with lower anti-Xa activity recorded during CPB had higher levels of thrombin-antithrombin complex (EST [SE]: +12.8 (4.7) ng/mL per -1 U/mL anti-Xa; P = .006); prothrombin activation fragment 1.2 (EST [SE]: +0.13 (0.07) log pg/mL per -1 U/mL anti-Xa; P = .06); and D-dimer (EST [SE]: -0.25 (0.09) log ng/mL per -1 U/mL anti-Xa; P = .009) in the postoperative period after adjustment for baseline antithrombin activity, duration of CPB, amount of fresh frozen plasma and heparin used throughout surgery in multivariable models. CONCLUSIONS: Low circulating antithrombin activity is associated with lower heparin efficacy, which ultimately leads to a lower ability to suppress thrombin generation during CPB. Determination of risk factors for heparin resistance, and potentially, antithrombin replacement therapy, may individualize and improve anticoagulation treatment. PMID- 26553459 TI - Reimplantation of an anomalous left innominate artery with Kommerell diverticulum arising from a right aortic arch. PMID- 26553460 TI - Systematic review of the influence of enhanced recovery pathways in elective lung resection. AB - OBJECTIVE: Enhanced-recovery pathways aim to accelerate postoperative recovery and facilitate early hospital discharge. The aim of this systematic review was to summarize the evidence regarding the influence of this intervention in patients undergoing lung resection. METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Eight bibliographic databases (Medline, Embase, BIOSIS, CINAHL, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials) were searched for studies comparing postoperative outcomes in adult patients treated within an enhanced-recovery pathway or traditional care. Risk of bias was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Six studies fulfilled our selection criteria (1 randomized and 5 nonrandomized studies). All the nonrandomized studies reported shorter length of stay in the intervention group (difference, 1.2-9.1 days), but the randomized study reported no differences. There were no differences between groups in readmissions, overall complications, and mortality rates. Two nonrandomized studies reported reduction in hospital costs in the intervention group. Risk of bias favoring enhanced recovery pathways was high. CONCLUSIONS: A small number of low-quality comparative studies have evaluated the influence of enhanced-recovery pathways in patients undergoing lung resection. Some studies suggest that this intervention may reduce length of stay and hospital costs, but they should be interpreted in light of several methodologic limitations. This review highlights the need for well-designed trials to provide conclusive evidence about the role of enhanced-recovery pathways in this patient population. PMID- 26553461 TI - Multidisciplinary nutritional support for undernutrition in nursing home and home care: A cluster randomized controlled trial. AB - OBJECTIVE: To assess the effect of multidisciplinary nutritional support for undernutrition in older adults in nursing home and home-care identified with the validated Eating Validation Scheme (EVS). METHODS: An 11 wk cluster randomized trial with a home-care (3 clusters) or nursing home (3 clusters) setting as the unit of randomization. Before starting the study, a train-the-trainer course was performed to educate the nutrition coordinators. In addition to the nutrition coordinator, the participants assigned to the intervention group strategy received multidisciplinary nutrition support. Focus was on treatment of the potentially modifiable nutritional risk factors identified with the EVS, by involving the physiotherapist, registered dietitian, and occupational therapist, as relevant and independent of the municipality's ordinary assessment and referral system. Outcome parameters were quality of life (by means of EuroQol-5D 3L), physical performance (30-seconds chair stand), nutritional status (weight and hand-grip strength), oral care, fall incidents, hospital admissions, rehabilitation stay, moving to nursing homes (participants from home-care), and mortality. RESULTS: Respectively, 55 (46 from 2 home-care clusters) and 40 (18 from 1 home-care cluster) were identified with the EVS and comprised the intervention and control group. A difference after 11 wk in quality of life (0.758 [0.222] versus 0.534 [0.355], P = 0.001), 30-seconds chair stand (47% versus 17% improved, P = 0.005) and oral care (1.1 [0.3] versus 1.3 [0.5], P = 0.021) was observed. There was a almost significant difference in mortality (2% versus 13%, P = 0.079). CONCLUSIONS: Multidisciplinary nutritional support in older adults in nursing home and home-care could have a positive effect on quality of life, muscle strength, and oral care. PMID- 26553462 TI - Escherichia coli Pyruvate Dehydrogenase Complex Is an Important Component of CXCL10-Mediated Antimicrobial Activity. AB - Chemokines are best recognized for their role within the innate immune system as chemotactic cytokines, signaling and recruiting host immune cells to sites of infection. Certain chemokines, such as CXCL10, have been found to play an additional role in innate immunity, mediating CXCR3-independent killing of a diverse array of pathogenic microorganisms. While this is still not clearly understood, elucidating the mechanisms underlying chemokine-mediated antimicrobial activity may facilitate the development of novel therapeutic strategies effective against antibiotic-resistant Gram-negative pathogens. Here, we show that CXCL10 exerts antibacterial effects on clinical and laboratory strains of Escherichia coli and report that disruption of pyruvate dehydrogenase complex (PDHc), which converts pyruvate to acetyl coenzyme A, enables E. coli to resist these antimicrobial effects. Through generation and screening of a transposon mutant library, we identified two mutants with increased resistance to CXCL10, both with unique disruptions of the gene encoding the E1 subunit of PDHc, aceE. Resistance to CXCL10 also occurred following deletion of either aceF or lpdA, genes that encode the remaining two subunits of PDHc. Although PDHc resides within the bacterial cytosol, electron microscopy revealed localization of immunogold-labeled CXCL10 to the bacterial cell surface in both the E. coli parent and aceE deletion mutant strains. Taken together, our findings suggest that while CXCL10 interacts with an as-yet-unidentified component on the cell surface, PDHc is an important mediator of killing by CXCL10. To our knowledge, this is the first description of PDHc as a key bacterial component involved in the antibacterial effect of a chemokine. PMID- 26553463 TI - Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis. AB - Pneumonic plague represents the most severe form of disease caused by Yersinia pestis due to its ease of transmission, rapid progression, and high mortality rate. The Y. pestis outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and/or processed by Y. pestis in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A2 activities of Prdx6. In addition, we found that infection with wild-type Y. pestis reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with Deltapla Y. pestis, suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or Deltapla Y. pestis, Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function in vitro and reduce Prdx6 levels in vivo, the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague. PMID- 26553464 TI - The Stringent Response Regulator DksA Is Required for Salmonella enterica Serovar Typhimurium Growth in Minimal Medium, Motility, Biofilm Formation, and Intestinal Colonization. AB - Salmonella enterica serovar Typhimurium is a facultative intracellular human and animal bacterial pathogen posing a major threat to public health worldwide. Salmonella pathogenicity requires complex coordination of multiple physiological and virulence pathways. DksA is a conserved Gram-negative regulator that belongs to a distinct group of transcription factors that bind directly to the RNA polymerase secondary channel, potentiating the effect of the signaling molecule ppGpp during a stringent response. Here, we established that in S. Typhimurium, dksA is induced during the logarithmic phase and DksA is essential for growth in minimal defined medium and plays an important role in motility and biofilm formation. Furthermore, we determined that DksA positively regulates the Salmonella pathogenicity island 1 and motility-chemotaxis genes and is necessary for S. Typhimurium invasion of human epithelial cells and uptake by macrophages. In contrast, DksA was found to be dispensable for S. Typhimurium host cell adhesion. Finally, using the colitis mouse model, we found that dksA is spatially induced at the midcecum during the early stage of the infection and required for gastrointestinal colonization and systemic infection in vivo. Taken together, these data indicate that the ancestral stringent response regulator DksA coordinates various physiological and virulence S. Typhimurium programs and therefore is a key virulence regulator of Salmonella. PMID- 26553465 TI - Global Changes in Mycoplasma gallisepticum Phase-Variable Lipoprotein Gene vlhA Expression during In Vivo Infection of the Natural Chicken Host. AB - Mycoplasma gallisepticum is the primary etiologic agent of chronic respiratory disease in poultry, a disease largely affecting the respiratory tract and causing significant economic losses worldwide. Immunodominant proteins encoded by members of the variable lipoprotein and hemagglutinin (vlhA) gene family are thought to be important for mechanisms of M. gallisepticum-host interaction, pathogenesis, and immune evasion, but their exact role and the overall nature of their phase variation are unknown. To better understand these mechanisms, we assessed global transcriptomic vlhA gene expression directly from M. gallisepticum populations present on tracheal mucosae during a 7-day experimental infection in the natural chicken host. Here we report differences in both dominant and minor vlhA gene expression levels throughout the first week of infection and starting as early as day 1 postinfection, consistent with a functional role not dependent on adaptive immunity for driving phase variation. Notably, data indicated that, at given time points, specific vlhA genes were similarly dominant in multiple independent hosts, suggesting a nonstochastic temporal progression of dominant vlhA gene expression in the colonizing bacterial population. The dominant expression of a given vlhA gene was not dependent on the presence of 12-copy GAA trinucleotide repeats in the promoter region and did not revert to the predominate vlhA gene when no longer faced with host pressures. Overall, these data indicate that vlhA phase variation is dynamic throughout the earliest stages of infection and that the pattern of dominant vlhA expression may be nonrandom and regulated by previously unrecognized mechanisms. PMID- 26553466 TI - Accumulation of Regulatory T Cells and Chronic Inflammation in the Middle Ear in a Mouse Model of Chronic Otitis Media with Effusion Induced by Combined Eustachian Tube Blockage and Nontypeable Haemophilus influenzae Infection. AB - Nontypeable Haemophilus influenzae (NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using eustachian tube (ET) obstruction and NTHi (10(7) CFU) inoculation into the tympanic bulla, and we investigated the relationship between regulatory T cells (Treg) and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. Untreated mice served as controls. MEEs were used for bacterial counts and to measure the concentrations of cytokines. MEM were collected for histological evaluation and flow cytometric analysis. Inflammation of the MEM was prolonged throughout this study, and the incidence of NTHi culture-positive MEE was 38% at 2 months after inoculation. The levels of interleukin-1beta (IL-beta), tumor necrosis factor alpha, IL-10, and transforming growth factor beta were increased in the middle ear for up to 2 months after inoculation. CD4(+) CD25(+) FoxP3(+) Treg accumulated in the middle ear, and the percentage of Treg in the MEM increased for up to 2 months after inoculation. Treg depletion induced a 99.9% reduction of bacterial counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM, and our findings indicate that Treg confer infectious tolerance to NTHi in the middle ear. PMID- 26553467 TI - Discovery and Characterization of Human-Urine Utilization by Asymptomatic Bacteriuria-Causing Streptococcus agalactiae. AB - Streptococcus agalactiae causes both symptomatic cystitis and asymptomatic bacteriuria (ABU); however, growth characteristics of S. agalactiae in human urine have not previously been reported. Here, we describe a phenotype of robust growth in human urine observed in ABU-causing S. agalactiae (ABSA) that was not seen among uropathogenic S. agalactiae (UPSA) strains isolated from patients with acute cystitis. In direct competition assays using pooled human urine inoculated with equal numbers of a prototype ABSA strain, designated ABSA 1014, and any one of several UPSA strains, measurement of the percentage of each strain recovered over time showed a markedly superior fitness of ABSA 1014 for urine growth. Comparative phenotype profiling of ABSA 1014 and UPSA strain 807, isolated from a patient with acute cystitis, using metabolic arrays of >2,500 substrates and conditions revealed unique and specific l-malic acid catabolism in ABSA 1014 that was absent in UPSA 807. Whole-genome sequencing also revealed divergence in malic enzyme-encoding genes between the strains predicted to impact the activity of the malate metabolic pathway. Comparative growth assays in urine comparing wild-type ABSA and gene-deficient mutants that were functionally inactivated for the malic enzyme metabolic pathway by targeted disruption of the maeE or maeK gene in ABSA demonstrated attenuated growth of the mutants in normal human urine as well as synthetic human urine containing malic acid. We conclude that some S. agalactiae strains can grow in human urine, and this relates in part to malic acid metabolism, which may affect the persistence or progression of S. agalactiae ABU. PMID- 26553468 TI - Suppression of CD4+ Effector Responses by Naturally Occurring CD4+ CD25+ Foxp3+ Regulatory T Cells Contributes to Experimental Cerebral Malaria. AB - The role of naturally occurring CD4(+) CD25(+) Foxp3(+) regulatory T cells (nTreg) in the pathogenesis of cerebral malaria (CM), which involves both pathogenic T cell responses and parasite sequestration in the brain, is still unclear. To assess the contribution and dynamics of nTreg during the neuropathogenesis, we unbalanced the ratio between nTreg and naive CD4(+) T cells in an attenuated model of Plasmodium berghei ANKA-induced experimental CM (ECM) by using a selective cell enrichment strategy. We found that nTreg adoptive transfer accelerated the onset and increased the severity of CM in syngeneic C57BL/6 (B6) P. berghei ANKA-infected mice without affecting the level of parasitemia. In contrast, naive CD4(+) T cell enrichment prevented CM and promoted parasite clearance. Furthermore, early during the infection nTreg expanded in the spleen but did not efficiently migrate to the site of neuroinflammation, suggesting that nTreg exert their pathogenic action early in the spleen by suppressing the protective naive CD4(+) T cell response to P. berghei ANKA infection in vivo in both CM-susceptible (B6) and CM-resistant (B6 CD4(-/-)) mice. However, their sole transfer was not sufficient to restore CM susceptibility in two CM-resistant congenic strains tested. Altogether, these results demonstrate that nTreg are activated and functional during P. berghei ANKA infection and that they contribute to the pathogenesis of CM. They further suggest that nTreg may represent an early target for the modulation of the immune response to malaria. PMID- 26553470 TI - Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides. AB - Cystic fibrosis (CF), the most common life-threatening genetic disease in Caucasians, is caused by ~2,000 different mutations in the CF transmembrane conductance regulator (CFTR) gene. A significant fraction of these (~13%) affect pre-mRNA splicing for which novel therapies have been somewhat neglected. We have previously described the effect of the CFTR splicing mutation c.2657+5G>A in IVS16, showing that it originates transcripts lacking exon 16 as well as wild type transcripts. Here, we tested an RNA-based antisense oligonucleotide (AON) strategy to correct the aberrant splicing caused by this mutation. Two AONs (AON1/2) complementary to the pre-mRNA IVS16 mutant region were designed and their effect on splicing was assessed at the RNA and protein levels, on intracellular protein localization and function. To this end, we used the 2657+5G>A mutant CFTR minigene stably expressed in HEK293 Flp-In cells that express a single copy of the transgene. RNA data from AON1-treated mutant cells show that exon 16 inclusion was almost completely restored (to 95%), also resulting in increased levels of correctly localized CFTR protein at the plasma membrane (PM) and with increased function. A novel two-color CFTR splicing reporter minigene developed here allowed the quantitative monitoring of splicing by automated microscopy localization of CFTR at the PM. The AON strategy is thus a promising therapeutic approach for the specific correction of alternative splicing. PMID- 26553469 TI - Toxoplasma gondii GRA7-Induced TRAF6 Activation Contributes to Host Protective Immunity. AB - The intracellular parasite Toxoplasma gondii has unique dense granule antigens (GRAs) that are crucial for host infection. Emerging evidence suggests that GRA7 of T. gondii is a promising serodiagnostic marker and an effective toxoplasmosis vaccine candidate; however, little is known about the intracellular regulatory mechanisms involved in the GRA7-induced host responses. Here we show that GRA7 induced MyD88 signaling through the activation of TRAF6 and production of reactive oxygen species (ROS) is required for the induction of NF-kappaB-mediated proinflammatory responses by macrophages. GRA7 stimulation resulted in the rapid activation of mitogen-activated protein kinases and an early burst of ROS in macrophages in a MyD88-dependent manner. GRA7 induced a physical association between GRA7 and TRAF6 via MyD88. Remarkably, the C terminus of GRA7 (GRA7-V) was sufficient for interaction with and ubiquitination of the RING domain of TRAF6, which is capable of inflammatory cytokine production. Interestingly, the generation of ROS and TRAF6 activation are mutually dependent on GRA7/MyD88 mediated signaling in macrophages. Furthermore, mice immunized with GRA7-V showed markedly increased Th1 immune responses and protective efficacy against T. gondii infection. Collectively, these results provide novel insight into the crucial role of GRA7-TRAF6 signaling in innate immune responses. PMID- 26553471 TI - Couch height-based patient setup for abdominal radiation therapy. AB - There are 2 methods commonly used for patient positioning in the anterior posterior (A-P) direction: one is the skin mark patient setup method (SMPS) and the other is the couch height-based patient setup method (CHPS). This study compared the setup accuracy of these 2 methods for abdominal radiation therapy. The enrollment for this study comprised 23 patients with pancreatic cancer. For treatments (539 sessions), patients were set up by using isocenter skin marks and thereafter treatment couch was shifted so that the distance between the isocenter and the upper side of the treatment couch was equal to that indicated on the computed tomographic (CT) image. Setup deviation in the A-P direction for CHPS was measured by matching the spine of the digitally reconstructed radiograph (DRR) of a lateral beam at simulation with that of the corresponding time integrated electronic portal image. For SMPS with no correction (SMPS/NC), setup deviation was calculated based on the couch-level difference between SMPS and CHPS. SMPS/NC was corrected using 2 off-line correction protocols: no action level (SMPS/NAL) and extended NAL (SMPS/eNAL) protocols. Margins to compensate for deviations were calculated using the Stroom formula. A-P deviation > 5mm was observed in 17% of SMPS/NC, 4% of SMPS/NAL, and 4% of SMPS/eNAL sessions but only in one CHPS session. For SMPS/NC, 7 patients (30%) showed deviations at an increasing rate of > 0.1mm/fraction, but for CHPS, no such trend was observed. The standard deviations (SDs) of systematic error (Sigma) were 2.6, 1.4, 0.6, and 0.8mm and the root mean squares of random error (sigma) were 2.1, 2.6, 2.7, and 0.9mm for SMPS/NC, SMPS/NAL, SMPS/eNAL, and CHPS, respectively. Margins to compensate for the deviations were wide for SMPS/NC (6.7mm), smaller for SMPS/NAL (4.6mm) and SMPS/eNAL (3.1mm), and smallest for CHPS (2.2mm). Achieving better setup with smaller margins, CHPS appears to be a reproducible method for abdominal patient setup. PMID- 26553472 TI - Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma. AB - Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose volume histogram (DVH) analysis, and a review of the relevant literature are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients. PMID- 26553473 TI - A comparison between radiation therapists and medical specialists in the use of kilovoltage cone-beam computed tomography scans for potential lung cancer radiotherapy target verification and adaptation. AB - Target volume matching using cone-beam computed tomography (CBCT) is the preferred treatment verification method for lung cancer in many centers. However, radiation therapists (RTs) are trained in bony matching and not soft tissue matching. The purpose of this study was to determine whether RTs were equivalent to radiation oncologists (ROs) and radiologists (RDs) in alignment of the treatment CBCT with the gross tumor volume (GTV) defined at planning and in delineating the GTV on the treatment CBCT, as may be necessary for adaptive radiotherapy. In this study, 10 RTs, 1 RO, and 1 RD performed a manual tumor alignment and correction of the planning GTV to a treatment CBCT to generate an isocenter correction distance for 15 patient data sets. Participants also contoured the GTV on the same data sets. The isocenter correction distance and the contoured GTVs from the RTs were compared with the RD and RO. The mean difference in isocenter correction distances was 0.40cm between the RO and RD, 0.51cm between the RTs, and RO and 0.42cm between the RTs and RD. The 95% CIs were smaller than the equivalence limit of 0.5cm, indicating that the RTs were equivalent to the RO and RD. For GTV delineation comparisons, the RTs were not found to be equivalent to the RD or RO. The alignment of the planning defined GTV and treatment CBCT using soft tissue matching by the RTs has been shown to be equivalent to those by the RO and RD. However, tumor delineation by the RTs on the treatment CBCT was not equivalent to that of the RO and RD. Thus, it may be appropriate for RTs to undertake soft tissue alignment based on CBCT; however, further investigation may be necessary before RTs undertake delineation for adaptive radiotherapy purposes. PMID- 26553474 TI - Relationship between student selection criteria and learner success for medical dosimetry students. AB - Medical dosimetry education occupies a specialized branch of allied health higher education. Noted international shortages of health care workers, reduced university funding, limitations on faculty staffing, trends in learner attrition, and increased enrollment of nontraditional students force medical dosimetry educational leadership to reevaluate current admission practices. Program officials wish to select medical dosimetry students with the best chances of successful graduation. The purpose of the quantitative ex post facto correlation study was to investigate the relationship between applicant characteristics (cumulative undergraduate grade point average (GPA), science grade point average (SGPA), prior experience as a radiation therapist, and previous academic degrees) and the successful completion of a medical dosimetry program, as measured by graduation. A key finding from the quantitative study was the statistically significant positive correlation between a student's previous degree and his or her successful graduation from the medical dosimetry program. Future research investigations could include a larger research sample, representative of more medical dosimetry student populations, and additional studies concerning the relationship of previous work as a radiation therapist and the effect on success as a medical dosimetry student. Based on the quantitative correlation analysis, medical dosimetry leadership on admissions committees could revise student selection rubrics to place less emphasis on an applicant's undergraduate cumulative GPA and increase the weight assigned to previous degrees. PMID- 26553475 TI - Transcranial Direct Current Stimulation of the Leg Motor Cortex Enhances Coordinated Motor Output During Walking With a Large Inter-Individual Variability. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) can augment force generation and control in single leg joints in healthy subjects and stroke survivors. However, it is unknown whether these effects also result in improved force production and coordination during walking and whether electrode configuration influences these effects. OBJECTIVE: We investigated the effect of tDCS using different electrode configurations on coordinated force production during walking in a group of healthy subjects and chronic stroke survivors. METHODS: Ten healthy subjects and ten chronic stroke survivors participated in a randomized double-blinded crossover study. Subjects walked on an instrumented treadmill before and after 10 minutes of uni-hemispheric (UNI), dual-hemispheric (DUAL) or sham tDCS applied to the primary motor cortex. RESULTS: tDCS responses showed large inter-individual variability in both subject populations. In healthy subjects tDCS enhanced the coordinated output during walking as reflected in an increased positive work generation during propulsion. The effects of DUAL tDCS were clearer but still small (4.4% increase) compared to UNI tDCS (2.8% increase). In the chronic stroke survivors no significant effects of tDCS in the targeted paretic leg were observed. CONCLUSIONS: tDCS has potential to augment multi-joint coordinated force production during walking. The relative small contribution of the motor cortex in controlling walking might explain why the observed effects are rather small. Furthermore, a better understanding of the inter-individual variability is needed to optimize the effects of tDCS in healthy but especially stroke survivors. The latter is a prerequisite for clinical applicability. PMID- 26553476 TI - Blepharoptosis correction transconjunctivally using buried suture method: A prospective cohort study. AB - BACKGROUND: Blepharoptosis correction with minimal eyelid scarring is a desirable outcome. The aim of this study was to describe in detail our method of blepharoptosis correction transconjunctivally using buried suture method and to demonstrate its effectiveness. METHODS: From June 2012 to May 2013, we performed a blepharoptosis correction transconjunctivally using buried suture method on 458 eyelids in 245 patients. During this procedure, we utilized six separate threads to form multiple knots. This thread was transconjunctivally inserted into the point located above the superior tarsal margin involving the superior levator palpebral and Muller muscles. RESULTS: A total of 409 eyelids (89%) were successfully corrected. Undercorrection was encountered in 49 eyelids (25 patients). Of the 25 patients, only 16 patients were dissatisfied with the undercorrection and thus underwent reoperation. Three patients with asymmetric double eyelid ptosis also underwent reoperation. Five patients required reoperation to correct eyelid fold loosening, which occurred during the follow-up period. No major complications such as overcorrection, persistent irritation, and keratitis were observed. CONCLUSIONS: Using our technique, we could achieve the desired correction by accurately checking the rate of correction. We have demonstrated here excellent predictability and success rate in mild and moderate ptosis. We believe that a blepharoptosis correction transconjunctivally using buried suture method is an effective treatment method. PMID- 26553477 TI - Glycine induced culture-harvesting strategy for Botryococcus braunii. AB - The objective of this study was to investigate the effects of culture conditions, including carbon sources and concentration, culture period, and precondition time, on the production of extracellular polymeric substances (EPS) and its influence on microalgal flocculation. EPS are natural high molecule polymer, excreted by microalgae themselves. EPS can accelerate the formation of microbial aggregates through binding cells closely. Organic carbon sources, such as glucose, glycerol, acetate and glycine were compared to select the optimal source to stimulate EPS accumulation. Subsequently, the effect of culture period, glycine dose and precondition time on EPS production and its influence on biomass growth and flocculation efficiency were investigated. As the main parts of EPS, tightly bound EPS were found positively related to suspended solids concentration. However, the loosely bound EPS may weaken the floc structure, leading to poor water-cells separation. Under the optimal condition with culture period of 16 days, glycine dose of 0.5 g l(-1) and precondition time of 5 days, the biomass concentration increased from 1.49 to 2 g l(-1), and the maximum suspended solids concentration of 7.06% with biomass recovery rate of 70.6% was achieved. PMID- 26553478 TI - Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis. AB - Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The Fe(II)/alpha ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4'-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase. PMID- 26553480 TI - In this issue: advances in molecular pathology of inflammatory disorders. PMID- 26553481 TI - Real-time label-free quantitative fluorescence microscopy-based detection of ATP using a tunable fluorescent nano-aptasensor platform. AB - Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules. PMID- 26553482 TI - Modeling Testosterone Circadian Rhythm in Hypogonadal Males: Effect of Age and Circannual Variations. AB - The objective of this study was to characterize the baseline circadian rhythm of testosterone levels in hypogonadal men. A total of 859 baseline profiles of testosterone from hypogonadal men were included in this analysis. The circadian rhythm of the testosterone was described by a stretched cosine function. Model parameters were estimated using NONMEM((r)) 7.3. The effect of different covariates on the testosterone levels was investigated. Model evaluation was performed using non-parametric bootstrap and predictive checks. A stretched cosine function deeply improved the data goodness of fit compared to the standard trigonometric function (p < 0.001; DeltaOFV = -204). The effect of the age and the semester, defined as winter and spring versus summer and fall, were significantly associated with the baseline levels of testosterone (p < 0.001, DeltaOFV = -15.6, and p < 0.001, DeltaOFV = -47.0). Model evaluation procedures such as diagnostic plots, visual predictive check, and non-parametric bootstrap evidenced that the proposed stretched cosine function was able to model the time course of the diurnal testosterone levels in hypogonadal males with accuracy and precision. The circadian rhythm of the testosterone levels was better predicted by the proposed stretched cosine function than a standard cosine function. Testosterone levels decreased by 5.74 ng/dL (2.4%) every 10 years and were 19.3 ng/dL (8.1%) higher during winter and spring compared to summer and fall. PMID- 26553483 TI - Compositional Analysis of Ternary and Binary Chemical Mixtures by Surface Enhanced Raman Scattering at Trace Levels. AB - Surface-enhanced Raman scattering has been proven a powerful means in the fast detection and recognition of chemicals at trace levels, while quantitative analysis especially the compositional analysis of trace chemical mixtures remains a challenge. We report here a "triangle-rule" based on the principal component analysis (PCA) of surface-enhanced Raman scattering spectra, to calculate the composition of individual component of ternary chemical mixtures at trace levels, which can be simplified into the "balance-rule" for binary mixtures. We demonstrated the validity of the triangle-rule and balance-rule in estimating the composition of ternary and binary mixtures of methyl orange, methylene blue, and crystal violet with different molecular structures, and the validity for ternary and binary mixtures of three isomers of monochlorobiphenyl with very similar molecular structures. This idea might be also applicable to mixtures of more components at the trace levels. PMID- 26553484 TI - Visual impairment, but not hearing impairment, is independently associated with lower subjective well-being among individuals over 95 years of age: A population based study. AB - BACKGROUND: Sensory impairment affects an increasing number of elderly adults, with a negative psychological impact. Our objective was to examine the associations of visual and hearing impairment with subjective well-being (SWB), an important psychological concept defined by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB] among long-lived individuals (LLIs) over 95 years of age. METHODS: Data on 442 LLIs from the Rugao longevity cohort, a population-based study in Rugao, China, were analyzed. Graded classifications of visual and hearing impairment (none, mild, moderate, and severe) were constructed from self-reported items. Bivariate correlation and multiple regression analysis were performed to test the associations. RESULTS: Approximately 66.1% and 87.3% of the subjects reported varying degrees of visual and hearing impairment. Following the degree of vision impairment, LS, PA, and AB decreased linearly, whereas NA increased linearly (all p for trend<0.05). Vision was significantly related to LS (r=0.238, p<0.001), PA (r=0.142, p<0.01), NA (r= 0.157, p<0.001), and AB (r=0.206, p<0.001). After adjustment for multiple variables including functional ability, an important factor of SWB, the associations of vision impairment with LS, NA, and AB, while diminished, still existed. CONCLUSIONS: Visual impairment, but not hearing impairment, was independently associated with low SWB among LLIs, and functional ability may play a mediating role in the observed relationship. The findings indicate that rehabilitation targeted for those with reduced vision and functioning in long lived populations may be important for promoting well-being and quality of life. PMID- 26553485 TI - Risk factors for severe injury following indoor and outdoor falls in geriatric patients. AB - INTRODUCTION: This study was performed to examine the characteristics of indoor and outdoor falls in older patients and the factors related to severe injury in the emergency department (ED). METHODS: In total, 26,515 patients fell indoors and 19,581 outdoors. The general and clinical characteristics were compared between the two groups and factors associated with severe injury following the falls were evaluated. RESULTS: Younger males fell more frequently outdoors than indoors. The common activities during outdoor falls were sports and leisure activities. Environmental hazards lead to more outdoor falls than indoor falls. Factors associated with severe injury after indoor falls were transport to the ED by public ambulance or from another medical facility rather than individual transportation, fall from stairs rather than fell over, and a head and neck injury rather than a lower extremity injury. Factors related to severe injury after outdoor falls were male sex, transport to the ED by public ambulance or from another medical facility or by another method rather than individual transportation, state employed, fall from stairs rather than fell over, head and neck or thorax or abdomen injury rather than a lower extremity injury. CONCLUSION: Transport to the ED by public ambulance or from another medical facility, and head and neck injury were risks for severe injury following indoor and outdoor falls in elderly subjects. Efforts to identify the risk factors for severe injury and for falling itself are important to prevent and reduce fall injuries in elderly subjects. PMID- 26553486 TI - Durable efficacy of liraglutide in patients with type 2 diabetes and pronounced insulin-associated weight gain: 52-week results from the Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) randomized controlled trial. AB - BACKGROUND: Pronounced weight gain frequently complicates insulin therapy in patients with type 2 diabetes (T2DM). We have previously reported that addition of liraglutide for 26 weeks can reverse insulin-associated weight gain, decrease insulin dose and improve glycaemic control, as compared with continuation of standard insulin treatment. OBJECTIVES: To investigate whether the beneficial effects of liraglutide are sustained up to 52 weeks and whether similar effects could be obtained when liraglutide is added 6 months later. METHODS: Adult T2DM patients with >= 4% weight gain within 16 months of insulin therapy completing the first 26-week trial period of open-label addition of liraglutide 1.8 mg day( 1) (n = 26) versus continuation of standard insulin therapy (n = 24) were all treated with liraglutide for another 26 weeks. Results were analysed according to the intention-to-treat principle. RESULTS: Overall, 24 (92%) and 18 (75%) patients originally assigned to liraglutide and standard therapy, respectively, completed the study. Addition of liraglutide decreased body weight to a similar extend when given in the first 26 weeks (liraglutide group) or second 26 weeks (original standard therapy group): -4.4 vs. -4.3 kg (difference -0.32 kg, 95% confidence interval -2.2 to 1.6 kg; P = 0.74). Similar results were also seen in the two groups with regard to decrease in haemoglobin A1c (HbA1c ) (-0.77 vs. 0.66%; P = 0.23) and insulin dose (-28 vs. -26 U day(-1) ; P = 0.32). In both groups, 22% of patients could discontinue insulin. Continuation of liraglutide until 52 weeks led to sustained effects on body weight, HbA1c and insulin-dose requirements. CONCLUSION: In T2DM patients with pronounced insulin-associated weight gain, addition of liraglutide within 2 years leads to sustained reversal of body weight, improved glycaemic control and decrease in insulin dose. Thus, liraglutide offers a valuable therapeutic option. PMID- 26553487 TI - Nutritional Support for Athletic Performance. PMID- 26553488 TI - Re-Examining High-Fat Diets for Sports Performance: Did We Call the 'Nail in the Coffin' Too Soon? AB - During the period 1985-2005, studies examined the proposal that adaptation to a low-carbohydrate (<25 % energy), high-fat (>60 % energy) diet (LCHF) to increase muscle fat utilization during exercise could enhance performance in trained individuals by reducing reliance on muscle glycogen. As little as 5 days of training with LCHF retools the muscle to enhance fat-burning capacity with robust changes that persist despite acute strategies to restore carbohydrate availability (e.g., glycogen supercompensation, carbohydrate intake during exercise). Furthermore, a 2- to 3-week exposure to minimal carbohydrate (<20 g/day) intake achieves adaptation to high blood ketone concentrations. However, the failure to detect clear performance benefits during endurance/ultra-endurance protocols, combined with evidence of impaired performance of high-intensity exercise via a down-regulation of carbohydrate metabolism led this author to dismiss the use of such fat-adaptation strategies by competitive athletes in conventional sports. Recent re-emergence of interest in LCHF diets, coupled with anecdotes of improved performance by sportspeople who follow them, has created a need to re-examine the potential benefits of this eating style. Unfortunately, the absence of new data prevents a different conclusion from being made. Notwithstanding the outcomes of future research, there is a need for better recognition of current sports nutrition guidelines that promote an individualized and periodized approach to fuel availability during training, allowing the athlete to prepare for competition performance with metabolic flexibility and optimal utilization of all muscle substrates. Nevertheless, there may be a few scenarios where LCHF diets are of benefit, or at least are not detrimental, for sports performance. PMID- 26553489 TI - Hypohydration and Human Performance: Impact of Environment and Physiological Mechanisms. AB - Body water losses of >2 % of body mass are defined as hypohydration and can occur from sweat loss and/or diuresis from both cold and altitude exposure. Hypohydration elicits intracellular and extracellular water loss proportionate to water and solute deficits. Iso-osmotic hypovolemia (from cold and high-altitude exposure) results in greater plasma loss for a given water deficit than hypertonic hypovolemia from sweat loss. Hypohydration does not impair submaximal intensity aerobic performance in cold-cool environments, sometimes impairs aerobic performance in temperate environments, and usually impairs aerobic performance in warm-hot environments. Hypohydration begins to impair aerobic performance when skin temperatures exceed 27 degrees C, and with each additional 1 degrees C elevation in skin temperature there is a further 1.5 % impairment. Hypohydration has an additive effect on impairing aerobic performance in warm-hot high-altitude environments. A commonality of absolute hypovolemia (from plasma volume loss) combined with relative hypovolemia (from tissue vasodilation) is present when aerobic performance is impaired. The decrement in aerobic exercise performance due to hypohydration is likely due to multiple physiological mechanisms, including cardiovascular strain acting as the 'lynchpin', elevated tissue temperatures, and metabolic changes which are all integrated through the CNS to reduce motor drive to skeletal muscles. PMID- 26553490 TI - The Physiological Regulation of Skeletal Muscle Fatty Acid Supply and Oxidation During Moderate-Intensity Exercise. AB - Energy substrates that are important to the working muscle at moderate intensities are the non-esterified fatty acids (NEFAs) taken up from the circulation and NEFAs originating from lipolysis of the intramuscular triacylglycerol (IMTAG). Moreover, NEFA from lipolysis via lipoprotein lipase (LPL) in the muscle of the very-low-density lipoproteins and in the (semi) post prandial state chylomicrons may also contribute. In this review, the NEFA fluxes and oxidation by skeletal muscle during prolonged moderate-intensity exercise are described in terms of the integration of physiological systems. Steps involved in the regulation of the active muscle NEFA uptake include (1) increased energy demand; (2) delivery of NEFA to the muscle; (3) transport of NEFA into the muscle by NEFA transporters; and (4) activation of the NEFAs and either oxidation or re esterification into IMTAG. The increased metabolic demand of the exercising muscle is the main driving force for all physiological regulatory processes. It elicits functional hyperemia, increasing the recruitment of capillaries and muscle blood flow resulting in increased NEFA delivery and accessibility to NEFA transporters and LPL. It also releases epinephrine that augments adipose tissue NEFA release and thereby NEFA delivery to the active muscle. Moreover, NEFA transporters translocate to the plasma membrane, further increasing the NEFA uptake. The majority of the NEFAs taken up by the active muscle is oxidized and a minor portion is re-esterified to IMTAG. Net IMTAG lipolysis occurs; however, the IMTAG contribution to total fat oxidation is rather limited compared to plasma derived NEFA oxidation, suggesting a complex role and regulation of IMTAG utilization. PMID- 26553491 TI - Innovative Operations Measures and Nutritional Support for Mass Endurance Events. AB - Endurance and sporting events have increased in popularity and participation in recent years worldwide, and with this comes the need for medical directors to apply innovative operational strategies and nutritional support to meet such demands. Mass endurance events include sports such as cycling and running half, full and ultra-marathons with over 1000 participants. Athletes, trainers and health care providers can all agree that both participant outcomes and safety are of the utmost importance for any race or sporting event. While demand has increased, there is relatively less published guidance in this area of sports medicine. This review addresses public safety, operational systems, nutritional support and provision of medical care at endurance events. Significant medical conditions in endurance sports include heat illness, hyponatraemia and cardiac incidents. These conditions can differ from those typically encountered by clinicians or in the setting of low-endurance sports, and best practices in their management are discussed. Hydration and nutrition are critical in preventing these and other race-related morbidities, as they can impact both performance and medical outcomes on race day. Finally, the command and communication structures of an organized endurance event are vital to its safety and success, and such strategies and concepts are reviewed for implementation. The nature of endurance events increasingly relies on medical leaders to balance safety and prevention of morbidity while trying to help optimize athlete performance. PMID- 26553492 TI - Nutritional Support for Exercise-Induced Injuries. AB - Nutrition is one method to counter the negative impact of an exercise-induced injury. Deficiencies of energy, protein and other nutrients should be avoided. Claims for the effectiveness of many other nutrients following injuries are rampant, but the evidence is equivocal. The results of an exercise-induced injury may vary widely depending on the nature of the injury and severity. Injuries typically result in cessation, or at least a reduction, in participation in sport and decreased physical activity. Limb immobility may be necessary with some injuries, contributing to reduced activity and training. Following an injury, an inflammatory response is initiated and while excess inflammation may be harmful, given the importance of the inflammatory process for wound healing, attempting to drastically reduce inflammation may not be ideal for optimal recovery. Injuries severe enough for immobilization of a limb result in loss of muscle mass and reduced muscle strength and function. Loss of muscle results from reductions in basal muscle protein synthesis and the resistance of muscle to anabolic stimulation. Energy balance is critical. Higher protein intakes (2-2.5 g/kg/day) seem to be warranted during immobilization. At the very least, care should be taken not to reduce the absolute amount of protein intake when energy intake is reduced. There is promising, albeit preliminary, evidence for the use of omega-3 fatty acids and creatine to counter muscle loss and enhance hypertrophy, respectively. The overriding nutritional recommendation for injured exercisers should be to consume a well-balanced diet based on whole, minimally processed foods or ingredients made from whole foods. The diet composition should be carefully assessed and changes considered as the injury heals and activity patterns change. PMID- 26553493 TI - Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise. AB - Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta alanine (~3-6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing factor to fatigue. Furthermore, sodium bicarbonate, sodium citrate and sodium/calcium lactate supplementation have been employed in an attempt to increase the extracellular buffering capacity. Although all attempts have increased blood bicarbonate concentrations, evidence indicates that sodium bicarbonate (0.3 g/kg body mass) is the most effective in improving high intensity exercise performance. The evidence supporting the ergogenic effects of sodium citrate and lactate remain weak. These nutritional strategies are not without side effects, as gastrointestinal distress is often associated with the effective doses of sodium bicarbonate, sodium citrate and calcium lactate. Similarly, paresthesia (i.e. tingling sensation of the skin) is currently the only known side effect associated with beta-alanine supplementation, and it is caused by the acute elevation in plasma beta-alanine concentration after a single dose of beta-alanine. Finally, the co-supplementation of beta-alanine and sodium bicarbonate may result in additive ergogenic gains during high-intensity exercise, although studies are required to investigate this combination in a wide range of sports. PMID- 26553495 TI - Carbohydrate Dependence During Prolonged, Intense Endurance Exercise. AB - A major goal of training to improve the performance of prolonged, continuous, endurance events lasting up to 3 h is to promote a range of physiological and metabolic adaptations that permit an athlete to work at both higher absolute and relative power outputs/speeds and delay the onset of fatigue (i.e., a decline in exercise intensity). To meet these goals, competitive endurance athletes undertake a prodigious volume of training, with a large proportion performed at intensities that are close to or faster than race pace and highly dependent on carbohydrate (CHO)-based fuels to sustain rates of muscle energy production [i.e., match rates of adenosine triphosphate (ATP) hydrolysis with rates of resynthesis]. Consequently, to sustain muscle energy reserves and meet the daily demands of training sessions, competitive athletes freely select CHO-rich diets. Despite renewed interest in high-fat, low-CHO diets for endurance sport, fat-rich diets do not improve training capacity or performance, but directly impair rates of muscle glycogenolysis and energy flux, limiting high-intensity ATP production. When highly trained athletes compete in endurance events lasting up to 3 h, CHO-, not fat-based fuels are the predominant fuel for the working muscles and CHO, not fat, availability becomes rate limiting for performance. PMID- 26553494 TI - Carbohydrate Nutrition and Team Sport Performance. AB - The common pattern of play in 'team sports' is 'stop and go', i.e. where players perform repeated bouts of brief high-intensity exercise punctuated by lower intensity activity. Sprints are generally 2-4 s long and recovery between sprints is of variable length. Energy production during brief sprints is derived from the degradation of intra-muscular phosphocreatine and glycogen (anaerobic metabolism). Prolonged periods of multiple sprints drain muscle glycogen stores, leading to a decrease in power output and a reduction in general work rate during training and competition. The impact of dietary carbohydrate interventions on team sport performance have been typically assessed using intermittent variable speed shuttle running over a distance of 20 m. This method has evolved to include specific work to rest ratios and skills specific to team sports such as soccer, rugby and basketball. Increasing liver and muscle carbohydrate stores before sports helps delay the onset of fatigue during prolonged intermittent variable speed running. Carbohydrate intake during exercise, typically ingested as carbohydrate-electrolyte solutions, is also associated with improved performance. The mechanisms responsible are likely to be the availability of carbohydrate as a substrate for central and peripheral functions. Variable-speed running in hot environments is limited by the degree of hyperthermia before muscle glycogen availability becomes a significant contributor to the onset of fatigue. Finally, ingesting carbohydrate immediately after training and competition will rapidly recover liver and muscle glycogen stores. PMID- 26553496 TI - Weight Management for Athletes and Active Individuals: A Brief Review. AB - Weight management for athletes and active individuals is unique because of their high daily energy expenditure; thus, the emphasis is usually placed on changing the diet side of the energy balance equation. When dieting for weight loss, active individuals also want to preserve lean tissue, which means that energy restriction cannot be too severe or lean tissue is lost. First, this brief review addresses the issues of weight management in athletes and active individuals and factors to consider when determining a weight-loss goal. Second, the concept of dynamic energy balance is reviewed, including two mathematical models developed to improve weight-loss predictions based on changes in diet and exercise. These models are now available on the Internet. Finally, dietary strategies for weight loss/maintenance that can be successfully used with active individuals are given. Emphasis is placed on teaching the benefits of consuming a low-ED diet (e.g., high-fiber, high-water, low-fat foods), which allows for the consumption of a greater volume of food to increase satiety while reducing energy intake. Health professionals and sport dietitians need to understand dynamic energy balance and be prepared with effective and evidence-based dietary approaches to help athletes and active individuals achieve their body-weight goals. PMID- 26553498 TI - A new type of oxidative addition of an iodoarene to a Pd(II) complex. AB - Oxidative addition of N-(2-iodophenyl)formamide to Pd(dba)2 (dba = dibenzylideneacetone) in the presence of 4,4'-ditertbutyl-2,2'-bipyridine ((t)Bubpy) produces [Pd(C6H4NHCHO-2)I((t)Bubpy)] (1) which inserts 2-iodophenyl isocyanide to give [Pd{C(=NC6H4I-2)C6H4NHCHO-2}I((t)Bubpy)] (2). Dehydroiodination of 2 with Tl(acac) (acacH = acetylacetone) gives the stable Pd(IV) complex OC-6-35-[Pd{C,N,N-C(=NC6H4-2)C6H4NCHO-2}I((t)Bubpy)] (4) likely resulting from the spontaneous oxidative addition of the I-Ar moiety present in the unstable intermediate Pd(II) complex [Pd{C,N-C(=NC6H4I-2)C6H4NCHO 2}((t)Bubpy)] (3). The crystal structure of 4 shows various C-H...O hydrogen bonds resulting in chains of dimers stacked along the a axis. PMID- 26553497 TI - Resisted Sled Sprint Training to Improve Sprint Performance: A Systematic Review. AB - BACKGROUND: Based on recent findings regarding the mechanical determinants of sprint performance, resisted sled sprint (RSS) training may provide an effective tool for the improvement of sprint acceleration and maximal velocity. However, the volume and intensity for effective RSS training in different populations is unclear. OBJECTIVES: The primary objective was to evaluate the effectiveness of RSS training compared with unresisted sprint (URS) training, and the differential effects of sled load on RSS training outcomes. DATA SOURCES: STUDY ELIGIBILITY AND APPRAISAL: A systematic review was performed primarily using PubMed and SPORTDiscus databases. Peer-reviewed studies were accepted only if the participants used a sled towing device for a longitudinal intervention of resisted sprint training, and if RSS training was the primary difference in training intervention between groups. Effect size (ES) reported using Cohen's d was presented to compare the magnitude of effect between both dependent and independent groups. RESULTS: A total of 11 studies fulfilled the eligibility criteria. Sled loads were prescribed either as a percentage of body mass (%BM), a targeted reduction in velocity compared with unresisted sprint velocity (%V(dec)) or as an absolute load (kg). RSS training with 'light' (<10 %BM or <10 %V(dec)) loads provide 'small' decrements in acceleration (-1.5%, ES = 0.50) to 'moderate' improvements in maximal sprint velocity (2.4%, ES = 0.80) in sprint-trained individuals. 'Moderate' (10-19.9%BM or 10-14.9%V(dec)) to 'very heavy' (>30%BM or >30%V(dec)) sled loads provide 'trivial' to 'extremely large' improvements in acceleration performance (0.5-9.1%, ES = 0.14-4.00) in strength-trained or team sport individuals. Whether RSS training is more effective than URS training in the improvement of acceleration or maximal sprint velocity remains equivocal. CONCLUSIONS: RSS training is a novel training method with potential for the improvement of sprint performance, but its performance benefits over URS training remain to be conclusively demonstrated. Between-study comparisons are limited primarily by discrepancies in the training status and phase of the participants, and sled load prescription. Future work is required to define the optimal load and volume for RSS depending on the specific components of sprint performance to be enhanced. PMID- 26553499 TI - Cell mediated immune responses in the placenta following challenge of vaccinated pregnant heifers with Neospora caninum. AB - The aim of the present study was to investigate and correlate the cell-mediated immune response and pathological changes at the maternal-fetal interface of Neospora-challenged pregnant cattle previously immunized with live and inactivated experimental vaccines. Pregnant heifers naive to Neospora caninum were divided in 5 groups of 4 animals, each one immunized before mating: Group A heifers were intravenously (iv) immunized with 6.25 * 10(7) live tachyzoites of the NC-6 strain; group B heifers were immunized twice subcutaneously (sc) 3 weeks apart with native antigen extract of the NC-6 strain formulated with ISCOMs; group C heifers were sc immunized twice 3 weeks apart with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) of the NC-1 strain formulated with ISCOMs; group D heifers were sc injected with sterile phosphate-buffered saline (PBS) and group E heifers received sc ISCOM-matrix (ISCOMs without antigen). All groups were iv-challenged with 4.7 * 10(7) NC-1 tachyzoites at 70 days of gestation. Heifers were culled at day 104 of gestation and placentomes were examined to evaluate lesions and local cellular immune responses using histopathology, immunohistochemistry and real time-PCR. Immunohistochemistry was performed using bovine leucocyte specific antibodies. Cytokine expression and levels (IFN-gamma, IL-4, IL-10, IL-12 and TNF-alpha) were measured using real-time reverse transcription-PCR and ELISA, respectively. Minimal inflammation was observed in group A placentomes; while placentomes from group B, C, D and E had moderate to severe infiltration with CD3(+), CD4(+), gammadelta-T cells, CD8(+) cells and macrophages being more numerous in groups B and E placentomes, when compared with groups C and D (P<0.001). Cytokine levels were significantly increased in the caruncles of animals of groups B and C in comparison with the other animal groups (P < 0.001). The results from this study showed that the strongest cellular immune responses were observed in the placentomes of animals that were immunized with inactivated vaccines (groups B and C) and in the placentomes of animals that were sc-sham-inoculated (groups D and E). On the other hand, animals that were immunized with live tachyzoites showed a milder immune cell infiltration to the placenta possibly due to the existence of a protective systemic maternal immune response that helped to minimize N. caninum infection at the maternal-fetal interface. PMID- 26553500 TI - Substrate-Independent Robust and Heparin-Mimetic Hydrogel Thin Film Coating via Combined LbL Self-Assembly and Mussel-Inspired Post-Cross-linking. AB - In this work, we designed a robust and heparin-mimetic hydrogel thin film coating via combined layer-by-layer (LbL) self-assembly and mussel-inspired post-cross linking. Dopamine-grafted heparin-like/-mimetic polymers (DA-g-HepLP) with abundant carboxylic and sulfonic groups were synthesized by the conjugation of adhesive molecule, DA, which exhibited substrate-independent adhesive affinity to various solid surfaces because of the formation of irreversible covalent bonds. The hydrogel thin film coated substrates were prepared by a three-step reaction: First, the substrates were coated with DA-g-HepLP to generate negatively charged surfaces. Then, multilayers were obtained via LbL coating of chitosan and the DA g-HepLP. Finally, the noncovalent multilayers were oxidatively cross-linked by NaIO4. Surface ATR-FTIR and XPS spectra confirmed the successful fabrication of the hydrogel thin film coatings onto membrane substrates; SEM images revealed that the substrate-independent coatings owned 3D porous morphology. The soaking tests in highly alkaline, acid, and concentrated salt solutions indicated that the cross-linked hydrogel thin film coatings owned high chemical resistance. In comparison, the soaking tests in physiological solution indicated that the cross linked hydrogel coatings owned excellent long-term stability. The live/dead cell staining and morphology observations of the adhered cells revealed that the heparin-mimetic hydrogel thin film coated substrates had low cell toxicity and high promotion ability for cell proliferation. Furthermore, systematic in vitro investigations of protein adsorption, platelet adhesion, blood clotting, and blood-related complement activation confirmed that the hydrogel film coated substrates showed excellent hemocompatibility. Both the results of inhibition zone and bactericidal activity indicated that the gentamycin sulfate loaded hydrogel thin films had significant inhibition capability toward both Escherichia coli and Staphylococcus aureus bacteria. Combined the above advantages, it is believed that the designed heparin-mimetic hydrogel thin films may show high potential for applications in various biological and clinical fields, such as long-term hemocompatible and drug-loading materials for implants. PMID- 26553502 TI - Outbreak of Mysterious Illness Among Hospital Staff: Poisoning or Iatrogenic Reinforced Mass Psychogenic Illness? AB - BACKGROUND: Hospitals are rarely reported as settings for mass psychogenic illness (MPI). The present report scrutinizes an outbreak of probable MPI among hospital staff, with medical intervention reinforcing the course of the illness. CASE REPORT: Four of seven staff members in an emergency department became acutely ill with nonspecific symptoms. After uneventful observation they were discharged, but symptoms worsened at reassembly for debriefing. Poisoning with hydrogen sulfide was suspected, and the victims were transferred by helicopter for hyperbaric oxygen (HBO) treatment. During the following 9 days, 14 possible poisoning victims were identified, 6 of whom were transferred for HBO. After hospital stays with repeated HBO treatment and examinations without identification of significant physical disease, the majority of the 10 HBO treated victims remained symptomatic, some on prolonged sick leave. The ward was closed for several weeks during comprehensive but negative investigations for toxic chemicals. Clinical data and lack of indication of chemical exposure, together with an attack pattern with only some individuals becoming ill in a shared environment, suggest MPI. Iatrogenic influence from dramatic intervention was probably a strong driving force in the outbreak. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Awareness of MPI may prevent unnecessary and potentially harmful treatment as well as improve health care resilience, particularly with respect to preparedness. Outbreaks of illness in a group of symptomatic victims without indication of significant physical disease should be managed by observation and limited intervention. PMID- 26553504 TI - Conformational ensemble of human alpha-synuclein physiological form predicted by molecular simulations. AB - We perform here enhanced sampling simulations of N-terminally acetylated human alpha-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post translational modification leads to the formation of a transient amphipathic alpha-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions. PMID- 26553503 TI - Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress. AB - We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 A resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern. PMID- 26553505 TI - Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia amplifying bird. AB - Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host's health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird's energetic needs, which may result in an increase in transmission events. PMID- 26553506 TI - Infantile linear IgA/IgG bullous dermatosis. PMID- 26553507 TI - Partial Treatment Requests and Underlying Motives of Applicants for Gender Affirming Interventions. AB - INTRODUCTION: Historically, only individuals with a cross-gender identity who wanted to receive a full treatment, were eligible for "complete sex reassignment" consisting of feminizing/masculinizing hormone treatment and several surgical interventions including genital surgery (full treatment). Currently, it is unclear what motives underlie a request for hormones only or surgery only or a combination of hormones and surgery (e.g., a mastectomy), but no genital surgery (partial treatment). AIMS: The aims of this study were (i) to describe treatment requests of applicants at a specialized gender identity clinic in the Netherlands; and (ii) to explore the motives underlying a partial treatment request, including the role of (non-binary) gender identity. METHODS: Information was collected on all 386 adults who applied for treatment at the Center of Expertise on Gender Dysphoria of the VU University Medical Center in Amsterdam, the Netherlands, in the year 2013. Treatment requests were available for 360 individuals: 233 natal men (64.7%) and 127 natal women (35.3%). Treatment requests were systematically collected during assessment. Individuals were classified as either desiring a full or partial treatment. The motives behind a partial treatment request were collected and categorized as well. RESULTS: The majority of applicants at our gender identity clinic requested full treatment. Among those who requested partial treatment, the most reported underlying motive was surgical risks/outcomes. Only a small number of applicants requested partial treatment to bring their body into alignment with their non-binary gender identity. CONCLUSION: It becomes clear that partial treatment is requested by a substantial number of applicants. This emphasizes the need for gender identity clinics to provide information about the medical possibilities and limitations, and careful introduction and evaluation of non-standard treatment options. PMID- 26553508 TI - Inversion of Supramolecular Chirality by Sonication-Induced Organogelation. AB - Natural helical structures have inspired the formation of well-ordered peptide based chiral nanostructures in vitro. These structures have drawn much attention owing to their diverse applications in the area of asymmetric catalysts, chiral photonic materials, and nanoplasmonics. The self-assembly of two enantiomeric fluorinated aromatic dipeptides into ordered chiral fibrillar nanostructures upon sonication is described. These fibrils form organogels. Our results clearly indicate that fluorine-fluorine interactions play an important role in self assembly. Circular dichroism analysis revealed that both peptides (peptides 1 and 2), containing two fluorines, depicted opposite cotton effects in their monomeric form compared with their aggregated form. This shows that supramolecular chirality inversion took place during the stimuli-responsive self-aggregation process. Conversely, peptide 3, containing one fluorine, did not exhibit chirality inversion in sonication-induced organogelation. Therefore, our results clearly indicate that fluorination plays an important role in the organogelation process of these aromatic dipeptides. Our findings may have broad implications regarding the design of chiral nanostructures for possible applications such as chiroptical switches, asymmetric catalysis, and chiral recognitions. PMID- 26553509 TI - Theoretical and experimental investigation of doping M in ZnSe (M = Cd, Mn, Ag, Cu) clusters: optical and bonding characteristics. AB - The optical and bonding characteristics of doping ZnSe quantum dots (QDs) were investigated. Cd-, Mn-, Ag- and Cu-doped ZnSe were synthesized in aqueous solution. Theoretically, the intensity of the Cd-Se bond was similar to that of the Zn-Se bond, which illustrates that Cd can be doped into ZnSe materials at any ratio. We found that Mn-Se bonding was stronger than Zn-Se bonding. Ag-doped ZnSe nanoclusters show the same bonding and configuration as Cu-doped ZnSe. Moreover, Cd can be doped into ZnSe using both the substitution- and vacancy-doping method. For Mn-doped ZnSe clusters, small amounts of Mn impurity lead to stronger bonding with Se, but larger amounts of Mn impurity led to the formation of a Mn-Mn metal bond. The theoretical results show that it is difficult to form a vacancy-doping cluster for Mn-doped ZnSe materials. In experiments, the absorption and photoluminescence (PL) spectral wavelengths of Mn-doped ZnSe nanocrystals were the same as those of pure ZnSe nanocrystals, showing that the Mn impurity is not doped into ZnSe nanocrystals. Ag- and Cu-doped ZnSe nanocrystals have the same PL characteristics. The doping of an impurity is related to the solubility product, and not the bonding intensity. PMID- 26553510 TI - Comparison of the Sacco Triage Method Versus START Triage Using a Virtual Reality Scenario in Advance Care Paramedic Students. PMID- 26553512 TI - Therapy: PHD inhibitors correct anaemia in CKD. PMID- 26553515 TI - Inflammation: Differential effects of salt on immune cell activity. PMID- 26553514 TI - Hypertension-attributed nephropathy: what's in a name? AB - Unrelated disease processes commonly occur in non-diabetic individuals with mild to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1 associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants. PMID- 26553516 TI - Development: Modelling disease in kidney organoids. PMID- 26553519 TI - Hypertension: Haematopoietic COX-2 in salt-sensitive hypertension. PMID- 26553521 TI - Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus). AB - Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. PMID- 26553517 TI - Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. AB - Chronic kidney disease (CKD) is a common comorbidity in patients with type 2 diabetes mellitus (T2DM) and both conditions are increasing in prevalence. CKD is estimated to affect ~50% patients with T2DM globally, and its presence and severity markedly influences disease prognosis. CKD is more common in certain patient populations, including the elderly, those with youth-onset diabetes mellitus, those who are obese, certain ethnic groups, and disadvantaged populations. These same settings have also seen the greatest increase in the prevalence of T2DM, as exemplified by the increasing prevalence of T2DM in low-to middle income countries. Patients from low-to-middle income countries are often the least able to deal with the burden of T2DM and CKD and the health-care facilities of these countries least able to deal with the demand for equitable access to renal replacement therapies. The increasing prevalence of younger individuals with T2DM, in whom an accelerated course of complications can be observed, further adds to the global burden of CKD. Paradoxically, improvements in cardiovascular survival in patients with T2DM have contributed to patients surviving longer, allowing sufficient time to develop renal impairment. This Review explores how the changing epidemiology of T2DM has influenced the prevalence and incidence of associated CKD across different populations and clinical settings. PMID- 26553522 TI - Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs: A Comparison With Adolescent and Young Adults. AB - AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data. PMID- 26553523 TI - Improved quality and efficiency after the introduction of physician-led team triage in an emergency department. AB - BACKGROUND: Overcrowding in the emergency department (ED) may negatively affect patient outcomes, so different triage models have been introduced to improve performance. Physician-led team triage obtains better results than other triage models. We compared efficiency and quality measures before and after reorganization of the triage model in the ED at our county hospital. MATERIALS AND METHODS: We retrospectively compared two study periods with different triage models: nurse triage in 2008 (baseline) and physician-led team triage in 2012 (follow-up). Physician-led team triage was in use during day-time and early evenings on weekdays. Data were collected from electronic medical charts and the National Mortality Register. RESULTS: We included 20,073 attendances in 2008 and 23,765 in 2012. The time from registration to physician presentation decreased from 80 to 33 min (P < 0.001), and the length of stay decreased from 219 to 185 min (P < 0.001) from 2008 to 2012, respectively. All of the quality variables differed significantly between the two periods, with better results in 2012. The odds ratio for patients who left before being seen or before treatment was completed was 0.62 (95% confidence interval 0.54-0.72). The corresponding result for unscheduled returns was 0.36 (0.32-0.40), and for the mortality rates within 7 and 30 days 0.72 (0.59-0.88) and 0.84 (0.73-0.97), respectively. The admission rate was 37% at baseline and 32% at follow-up (P < 0.001). CONCLUSION: Physician led team triage improved the efficiency and quality in EDs. PMID- 26553524 TI - Floating Oscillator-Embedded Triboelectric Generator for Versatile Mechanical Energy Harvesting. AB - A versatile vibration energy harvesting platform based on a triboelectricity is proposed and analyzed. External mechanical vibration repeats an oscillating motion of a polymer-coated metal oscillator floating inside a surrounding tube. Continuous sidewall friction at the contact interface of the oscillator induces current between the inner oscillator electrode and the outer tube electrode to convert mechanical vibrations into electrical energy. The floating oscillator embedded triboelectric generator (FO-TEG) is applicable for both impulse excitation and sinusoidal vibration which universally exist in usual environment. For the impulse excitation, the generated current sustains and slowly decays by the residual oscillation of the floating oscillator. For the sinusoidal vibration, the output energy can be maximized by resonance oscillation. The operating frequency range can be simply optimized with high degree of freedom to satisfy various application requirements. In addition, the excellent immunity against ambient humidity is experimentally demonstrated, which stems from the inherently packaged structure of FO-TEG. The prototype device provides a peak-to peak open-circuit voltage of 157 V and instantaneous short-circuit current of 4.6 MUA, within sub-10 Hz of operating frequency. To visually demonstrate the energy harvesting behavior of FO-TEG, lighting of an array of LEDs is demonstrated using artificial vibration and human running. PMID- 26553525 TI - Thromboembolism and anticoagulation management in the preterm infant. AB - The incidence of preterm thromboembolism has been increasing due to advances in diagnostic imaging which allow better detection of thrombi in sick preterm infants. At the same time, improvement in neonatal intensive care unit supportive care has increased the number of surviving and living preterm infants with thromboembolic risk factors. Disruption in the fine balance of hemostasis with potential risk factors, specifically septicemia and indwelling catheters, increase the occurrence of thromboembolic events. Treatment strategies in preterm infants are challenging due to limited data. PMID- 26553527 TI - Iron-catalyzed transfer hydrogenation of imines assisted by an iron-based Lewis acid. AB - An iron-catalyzed transfer hydrogenation of N-aryl and N-alkyl imines using isopropanol as the hydrogen donor is reported for the first time. A combination of two iron complexes serving different roles is the key for the success of this catalytic system. As a result, an environmentally friendly and precious metal free transfer hydrogenation of imines has been developed. The use of a suitable co-catalyst as an activator not only led to efficient transfer hydrogenation, but also showed potential in enantioselective transformation. PMID- 26553526 TI - Combined Use of Oligopeptides, Fragment Libraries, and Natural Compounds: A Comprehensive Approach To Sample the Druggability of Vascular Endothelial Growth Factor. AB - The modulation of protein-protein interactions (PPIs) is emerging as a highly promising tool to fight diseases. However, whereas an increasing number of compounds are able to disrupt peptide-mediated PPIs efficiently, the inhibition of domain-domain PPIs appears to be much more challenging. Herein, we report our results related to the interaction between vascular endothelial growth factor (VEGF) and its receptor (VEGFR). The VEGF-VEGFR interaction is a typical domain domain PPI that is highly relevant for the treatment of cancer and some retinopathies. Our final goal was to identify ligands able to bind VEGF at the region used by the growth factor to interact with its receptor. We undertook an extensive study, combining a variety of experimental approaches, including NMR spectroscopy-based screening of small organic fragments, peptide libraries, and medicinal plant extracts. The key feature of the successful ligands that emerged from this study was their capacity to expose hydrophobic functional groups able to interact with the hydrophobic hot spots at the interacting VEGF surface patch. PMID- 26553528 TI - Predicting outcomes of emergency cerclage in women with cervical insufficiency using inflammatory markers in maternal blood and amniotic fluid. AB - OBJECTIVE: To identify inflammatory markers in maternal blood and amniotic fluid that can predict outcomes of emergency cerclage in women with cervical insufficiency. METHODS: This retrospective cohort study included patients at 18 24 weeks of pregnancy who underwent amniocentesis before receiving emergency cerclage for cervical insufficiency between August 2004 and August 2013 at a university teaching hospital in South Korea. Total and differential white blood cell counts were measured during amniocentesis. Amniotic fluid was cultured and analyzed for the presence of interleukin (IL)-6 and IL-8. The primary outcome measure was spontaneous preterm delivery (SPTD) at less than 32weeks of pregnancy following cerclage placement. RESULTS: Of 37 patients, 18 (49%) experienced SPTD at less than 32weeks of pregnancy. These patients were found to have significantly more advanced cervical dilatation at presentation, as well as higher mean neutrophil-lymphocyte ratios (NLRs) and higher IL-6 and IL-8 levels in amniotic fluid in comparison with those who did not experience SPTD at less than 32weeks of pregnancy. In a multivariable analysis, a high NLR and high amniotic fluid IL-8 levels showed a significant correlation with the occurrence of SPTD at less than 32weeks of pregnancy (P=0.032). CONCLUSION: Pre-operative NLR and amniotic fluid IL-8 levels may be important markers for predicting emergency cerclage outcomes in women with cervical insufficiency. PMID- 26553529 TI - Prognosis of papillary thyroid cancers with positive serum thyroglobulin antibody after total thyroidectomy. AB - BACKGROUND/OBJECTIVE: To investigate the influence of serum anti-thyroglobulin antibody (TgAb) on the prognosis in papillary thyroid cancer (PTC) patients. METHODS: In this retrospective study, the participants were enrolled from 1206 PTC patients (927 women, 279 men; mean age, 42.2 years) with T2 and higher, or N1 or M1 classifications in tumor-node-metastasis staging after total thyroidectomy. We recorded the final serum TgAb data (on thyroxin therapy) at the end of follow up in 2012. Patients were classified as negative TgAb or positive TgAb groups on the basis of their serum TgAb levels (< 70 IU/mL or >= 70 IU/mL). RESULTS: Among the 1206 patients, after mean follow-up for 11.6 +/- 6.1 years (range, 2.0-29.2 years), there were 75 with positive TgAb and 1131 with negative TgAb. Patient categorization depending on the follow-up time (2-5 years after surgery, 5-10 years after surgery, and 10-30 years after surgery) was performed. In comparison to traditional risk factors, such as age, tumor size, and sex, which were important prognostic factors for cancer recurrence and mortality in PTC patients, there was no significant difference in the prognosis between positive TgAb patients and negative TgAb patients by the multivariate analyses (cancer recurrence, p = 0.164, p = 0.112, p = 0.202, respectively; cancer mortality, p = 0.181, p = 0.646, p = 0.656, respectively) based on the different follow-up times. CONCLUSION: Positive serum TgAb was not a risk factor, and was not associated with the prognosis of PTC patients. PMID- 26553530 TI - Differential signalling and glutamate receptor compositions in the OFF bipolar cell types in the mouse retina. AB - KEY POINTS: Using whole-cell clamp methods, we characterized the temporal coding in each type of OFF bipolar cell. We found that type 2 and 3a cells are transient, type 1 and 4 cells are sustained, and type 3b cells are intermediate. The light-evoked excitatory postsynaptic potentials in some types were rectified, suggesting that they provide inputs to the non-linear ganglion cells. Visual signalling from the photoreceptors was mediated exclusively through the kainate receptors in the transient OFF bipolar cells, whereas both kainate and AMPA receptors contributed in the other cells. This study demonstrates, for the first time, that parallel visual encoding starts at the OFF bipolar cells in a type specific manner. ABSTRACT: The retina is the entrance to the visual system, which receives various kinds of image signals and forms multiple encoding pathways. The second-order retinal neurons, the bipolar cells, are thought to initiate multiple neural streams by encoding various visual signals in different types of cells. However, the functions of each bipolar cell type have not been fully understood. We investigated whether OFF bipolar cells encode visual signals in a type dependent manner. We recorded the changes in the bipolar cell voltage in response to two input functions: step and sinusoidal light stimuli. Type 1 and 4 OFF bipolar cells were sustained cells and responded to sinusoidal stimuli over a broad range of frequencies. Type 2 and 3a cells were transient and exhibited band pass filtering. Type 3b cells were in the middle of these two groups. The distinct temporal responses might be attributed to different types of glutamate receptors. We examined the AMPA and kainate glutamate receptor composition in each bipolar cell type. The light responses in the transient OFF bipolar cells were exclusively mediated by kainate receptors. Although the kainate receptors mediated the light responses in the sustained cells, the AMPA receptors also mediated a portion of the responses in sustained cells. Furthermore, we found that some types of cells were rectified more than other types. Taken together, we found that the OFF bipolar cells encode diverse temporal image signals in a type dependent manner, confirming that each type of OFF bipolar cell initiates diverse temporal visual processing in parallel. PMID- 26553532 TI - Estimation of interaction effects using pooled biospecimens in a case-control study. AB - Pooling, or physically mixing biospecimens, prior to evaluating biomarkers dramatically reduces biomarker evaluation cost, reduces the quantity of biospecimens required of each individual, and may reduce the percentage of laboratory measurements below the lower limit of detection. Motivated by a case control study on miscarriage (binary outcome) and cytokines (continuous exposures), we are interested in estimating parameters in a logistic regression, where individuals with the same disease status (with or without a miscarriage) are paired and their pooled cytokine concentrations are assessed. Previous research has proposed a set-based logistic model to evaluate the relationship between a disease and pooled exposures. While the set-based logistic model is very useful for estimating main effects, it cannot estimate interactions of continuous exposures when both are measured in pools. Therefore, we propose using the expectation maximization (EM) algorithm to obtain estimators of all parameters in logistic regression model, including interactions effects. Using a simulation study, we present comparisons of efficiency under different scenarios where exposures have been measured in pools and individually. Our simulations show that randomly sampling half of the available biospecimens has less efficiency than pooling pairs of biospecimens stratified by disease status. The EM algorithm provides a method for estimating interaction effects when biospecimens have already been pooled for other reasons such as the gain in efficiency for estimating main effects demonstrated by previous research. This manuscript demonstrates that the EM algorithm offers a promising approach to estimate interaction effects of pooled biospecimens. PMID- 26553533 TI - Subsequent pregnancy outcome after preterm breech delivery, a population based cohort study. AB - OBJECTIVE: The objective of this study is to investigate the effect of the mode of delivery in women with preterm breech presentation on neonatal and maternal outcome in the subsequent pregnancy. METHODS: Nationwide population-based cohort study in the Netherlands of women with a preterm breech delivery and a subsequent delivery in the years 1999-2007. We compared planned caesarean section versus planned vaginal delivery for perinatal outcomes in both pregnancies. RESULTS: We identified 1543 women in the study period, of whom 259 (17%) women had a planned caesarean section and 1284 (83%) women had a planned vaginal delivery in the first pregnancy. In the subsequent pregnancy, perinatal mortality was 1.1% (3/259) for women with a planned caesarean section in the first pregnancy and 0.5% (6/1284) for women with a planned vaginal delivery in the first pregnancy (aOR 1.8; 95% CI 0.31-10.1). Composite adverse neonatal outcome was 2.3% (6/259) versus 1.5% (19/1284), (aOR 1.5; 95% CI 0.55-4.2). The average risk of perinatal mortality over two pregnancies was 1.9% (10/518) for planned caesarean section and 2.0% (51/2568) for planned vaginal delivery, (OR 0.98; 95% CI 0.49-1.9). CONCLUSION: In women with a preterm breech delivery, planned caesarean section does not reduce perinatal mortality, perinatal morbidity, or maternal morbidity rate over the course of two pregnancies. PMID- 26553534 TI - Two cases of cardiac sarcoidosis diagnosed based on biopsy results of the gluteus muscle with focal uptake of 18F-fluorodeoxyglucose. PMID- 26553531 TI - Suppressed glycolytic metabolism in the prostate of transgenic rats overexpressing calcium-binding protein regucalcin underpins reduced cell proliferation. AB - Regucalcin (RGN) is a calcium-binding protein underexpressed in human prostate cancer cases, and it has been associated with the suppression of cell proliferation and the regulation of several metabolic pathways. On the other hand, it is known that the metabolic reprogramming with augmented glycolytic metabolism and enhanced proliferative capability is a characteristic of prostate cancer cells. The present study investigated the influence of RGN on the glycolytic metabolism of rat prostate by comparing transgenic adult animals overexpressing RGN (Tg-RGN) with their wild-type counterparts. Glucose consumption was significantly decreased in the prostate of Tg-RGN animals relatively to wild-type, and accompanied by the diminished expression of glucose transporter 3 and glycolytic enzyme phosphofructokinase. Also, prostates of Tg RGN animals displayed lower lactate levels, which resulted from the diminished expression/activity of lactate dehydrogenase. The expression of the monocarboxylate transporter 4 responsible for the export of lactate to the extracellular space was also diminished with RGN overexpression. These results showed the effect of RGN in inhibiting the glycolytic metabolism in rat prostate, which was underpinned by a reduced cell proliferation index. The present findings also suggest that the loss of RGN may predispose to a hyper glycolytic profile and fostered proliferation of prostate cells. PMID- 26553535 TI - Left atrial appendage to great cardiac vein fistula complicating watchman left atrial appendage closure. PMID- 26553536 TI - A migrating vascular haemostatic clip induced myocardial infarction 8 years after pulmonary lobectomy: successful percutaneous treatment with a distal protection basket. PMID- 26553537 TI - Fully integrated whole-body [18F]-fludeoxyglucose positron emission tomography/magnetic resonance imaging in therapy monitoring of giant cell arteritis. PMID- 26553538 TI - A rare cause of tough coronary occlusion. PMID- 26553539 TI - Corevalve Evolut R implantation to treat severe left ventricle outflow tract obstruction following mitral valve-in-ring: first-in-man report. PMID- 26553540 TI - MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart. AB - AIMS: Recent randomized trials suggest that intensive glycaemic control fails to reduce heart failure-related events in patients with diabetes. The molecular cues underlying persistent myocardial damage despite normoglycaemia restoration remain elusive. MicroRNAs (miRNAs), a class of small non-coding RNAs, orchestrate transcriptional programs implicated in adverse cardiac remodelling. The present study investigates whether miRNAs participate to hyperglycaemic memory in the diabetic heart. METHODS AND RESULTS: miRNA landscape was assessed by Mouse miRNome miRNA PCR Arrays in left ventricular specimens collected from 4-month-old streptozotocin-induced diabetic mice, with or without intensive glycaemic control by slow-release insulin implants. A dysregulation of 316 out of 1008 total miRNAs was observed in the diabetic hearts when compared with controls. Of these, 209 were up-regulated and 107 were down-regulated by >2.0-fold. Interestingly enough, the expression of 268 of those miRNAs remained significantly altered in diabetic mice even after subsequent normoglycaemia. Ingenuity pathway analysis revealed that dysregulated miRNAs were implicated in myocardial signalling networks triggering apoptosis (miR-320b, miR-378, miR-34a), fibrosis (miR-125b, miR-150, miR-199a, miR-29b, miR30a), hypertrophic growth (miR-1, miR-150, miR-199a, miR 133a, miR-214, miR-29a, miR-125b, miR-221, miR-212), autophagy (miR-133a, miR 221, miR-212, miR30a), oxidative stress (miR-221, miR-146a, miR-34a, miR-210, miR 19b, miR-125b, miR27a, miR-155), and heart failure (miR-423, miR-499, miR-199a), respectively. CONCLUSIONS: Glycaemic control is not able to rescue hyperglycaemia induced alterations of miRNA landscape in the diabetic heart. These findings may provide novel insights to understand why diabetic cardiomyopathy progresses despite normalization of blood glucose levels. PMID- 26553541 TI - Valve weight in aortic stenosis: back to the basics. PMID- 26553544 TI - New-onset diabetes in hypertensive patients and mortality: timing is everything. PMID- 26553543 TI - Extensive myocardial calcinosis due to Mycobacterium tuberculosis. PMID- 26553545 TI - Living up to its name? The effect of salinity on development, growth, and phenotype of the "marine" toad (Rhinella marina). AB - The highly permeable integument of amphibians renders them vulnerable to chemical characteristics of their environment, especially during the aquatic larval stage. As the cane toad (Rhinella marina, Bufonidae) invades southwards along the east coast of Australia, it is encountering waterbodies with highly variable conditions of temperature, pH, and salinity. Understanding the tolerance of toads to these conditions can clarify the likely further spread of the invader, as well as the adaptability of the species to novel environmental challenges. We measured salinity in waterbodies in the field and conducted laboratory trials to investigate the impacts of salinity on toad viability. Eggs and tadpoles from the southern invasion front tolerated the most saline conditions we found in potential spawning ponds during surveys [equivalent to 1200 ppm (3.5 % the salinity of seawater)]. Indeed, high-salinity treatments increased tadpole body sizes, accelerated metamorphosis, and improved locomotor ability of metamorphs (but did not affect metamorph morphology). At very low salinity [40 ppm (0.1 % seawater)], eggs hatched but larvae did not develop past Gosner stage 37. Our study shows that the egg and larval life stages of cane toads can tolerate wide variation in the salinity of natal ponds and that this aspect of waterbody chemistry is likely to facilitate rather than constrain continued southward expansion of the toad invasion front in eastern Australia. PMID- 26553551 TI - An incidental pulmonary part-solid ground-glass nodule in a patient under anticoagulant therapy. PMID- 26553552 TI - Age-related methylation profiles of equine blood leukocytes in the RNASEL locus. AB - Methylation profiles across three CpG islands of the RNASEL gene were determined in blood leukocyte samples of Anglo-Arabian and Hucul horses. Bisulfite sequencing revealed hypomethylated state of the RNASEL promoter coinciding with methylated CpG island placed inside the gene. Several CpG sites were identified for which the methylation state was influenced by DNA polymorphism. Two of them showed monoallelic methylation. One of the CpG sites revealed functional polymorphism. A number of partially methylated CpG sites have been observed in the promoter area of RNASEL, which were used for the comparison of breed- and age related effects. Clone bisulfite sequencing of blood leukocyte samples collected at different ages from particular individuals of AA and HC breeds and, also, BSPCR sequencing of 50 samples of juvenile and old AA and HC horses revealed increased methylation in particular CpG sites during aging. The age-related heterogeneity of white blood cells was hypothesized as being one of the potential causes of observed variability of methylation profiles in the RNASEL promoter. PMID- 26553553 TI - Cardiac and somatic parameters in zebrafish: tools for the evaluation of cardiovascular function. AB - Cardiovascular diseases are a worldwide public health problem. To date, extensive research has been conducted to elucidate the pathophysiological mechanisms that trigger cardiovascular diseases and to evaluate therapeutic options. Animal models are widely used to achieve these goals, and zebrafish have emerged as a low-cost model that produces rapid results. Currently, a large body of research is devoted to the cardiovascular development and diverse cardiovascular disorders of zebrafish embryos and larvae. However, less research has been conducted on adult zebrafish specimens. In this study, we evaluated a method to obtain and to evaluate morphometric parameters (of both the entire animal and the heart) of adult zebrafish. We used these data to calculate additional parameters, such as body mass index, condition factor and cardiac somatic index. This method and its results can be used as reference for future studies that aim to evaluate the pathophysiological aspects of the zebrafish cardiovascular system. PMID- 26553554 TI - Attenuation of the adverse effects caused by the foot-and-mouth disease vaccination in pigs. PMID- 26553555 TI - A biomimetic approach to hormone resistant prostate cancer cell isolation using inactivated Sendai virus (HVJ-E). AB - Our study reports a versatile immobilization method of Hemagglutinating Virus of Japan Envelope (HVJ-E) for the generation of viral-mimetic surfaces for hormone resistant prostate cancer cell isolation. HVJ-E has recently attracted much attention as a new type of therapeutic material because hormone resistant prostate cancer cells such as PC-3 cells possess the HVJ-E receptors, GD1a. The HVJ-E was successfully immobilized on precursor films composed of poly-l-lysine and alginic acid via layer-by-layer assembly without changing the biological activity. The monolayer adsorption of HVJ-E particles was confirmed by quartz crystal microbalance, fluorescent and atomic force microscopy analyses. By developing the HVJ-E coating with an affinity based cell trap within a glass capillary tube, we are able to gently isolate PC-3 from LN-Cap cells that represent adenocarcinoma without compromising cell viability. We achieved approximately 100% cell separation efficiency only by 60 seconds of flowing. We believe that the proposed technique offers significant promise for the creation of a hormone resistant cancer cell trap on a broad range of materials. PMID- 26553559 TI - Ice nucleation active particles are efficiently removed by precipitating clouds. AB - Ice nucleation in cold clouds is a decisive step in the formation of rain and snow. Observations and modelling suggest that variations in the concentrations of ice nucleating particles (INPs) affect timing, location and amount of precipitation. A quantitative description of the abundance and variability of INPs is crucial to assess and predict their influence on precipitation. Here we used the hydrological indicator delta(18)O to derive the fraction of water vapour lost from precipitating clouds and correlated it with the abundance of INPs in freshly fallen snow. Results show that the number of INPs active at temperatures >= -10 degrees C (INPs-10) halves for every 10% of vapour lost through precipitation. Particles of similar size (>0.5 MUm) halve in number for only every 20% of vapour lost, suggesting effective microphysical processing of INPs during precipitation. We show that INPs active at moderate supercooling are rapidly depleted by precipitating clouds, limiting their impact on subsequent rainfall development in time and space. PMID- 26553557 TI - Uric acid enhances the antitumor immunity of dendritic cell-based vaccine. AB - Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-gamma. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies. PMID- 26553560 TI - Generation of a soluble recombinant trimeric form of bovine CD40L and its potential use as a vaccine adjuvant in cows. AB - Vaccination is the most cost-effective way to control infectious diseases in cattle. However, many infectious diseases leading to severe economical losses worldwide still remain for which a really effective and safe vaccine is not available. These diseases are most often due to intracellular pathogens such as bacteria or viruses, which are, by their localization, protected from antibiotics and/or CD4(+) T cell-dependent humoral responses. We therefore postulated that strategies leading to induction of not only CD4(+) T cell responses but also CD8(+) cytotoxic T lymphocyte (CTL) responses against infected cells should be privileged in the development of new vaccines against problematic intracellular pathogens in bovines. CD40 signaling in antigen-presenting cells may lead to the induction of robust CD4-independent CTL responses and several studies, especially in mice, have used CD40 stimulation to promote CD8(+) T cell-mediated immunity. For example, we have recently shown that immunization of mice with heat-killed Staphylococcus aureus (HKSA) and agonistic anti-CD40 monoclonal antibodies elicits strong CTL responses capable of protecting mice from subsequent staphylococcal mastitis. Unfortunately, there is at present no tool available to efficiently stimulate CD40 in cattle. In this study, we therefore first produced a soluble recombinant trimeric form of the natural bovine CD40 ligand (sboCD40LT). We then observed that sboCD40LT was able to potently stimulate bovine cells in vitro. Finally, we provide evidence that immunization of cows with sboCD40LT combined with HKSA was able to significantly increase the number of both HKSA-specific CD4(+) and CD8(+) T cells in the draining lymph nodes. In conclusion, we suggest that this new molecular tool could help in the development of vaccine strategies against bovine diseases caused by intracellular pathogens. PMID- 26553561 TI - Avian CD25(+) gamma/delta (gammadelta) T cells after Salmonella exposure. AB - Although an expansion of distinct gammadelta T-lymphocyte subpopulations has been shown after Salmonella infection of chicks, functions and activation states of these cells are still largely unknown. To characterize the activation status of avian gammadelta T lymphocytes after Salmonella exposure, an avian whole-blood Salmonella Enteritidis live-vaccine-strain (SE-LV) stimulation assay and flow cytometry were used, and the bacteria-provoked CD25-antigen expression of CD8 characterized gammadelta T-cell subsets determined in comparison to alphabeta T cells. In non-stimulated controls, low numbers of CD25-positive cells were observed in all T-cell populations. The SE-LV stimulation resulted in a significantly enhanced percentage of CD25-expressing CD8alpha(-), CD8alpha(lo+) and CD8alphaalpha(hi+) gammadelta T cells accompanied by an increased intensity of the CD25 expression of these cells. Highest values were always seen within the CD8alphaalpha(hi+) gammadelta T-lymphocyte subset. The alphabeta T cells showed no changed CD25 expression. In conclusion, the increased CD25 expression on discrete peripheral T-lymphocyte populations after ex vivo stimulation demonstrates a Salmonella-induced activation of gammadelta T-cell subsets and underlines the unique, probably activated character, especially of the avian CD8alphaalpha(hi+) gammadelta T cells. PMID- 26553562 TI - Mutational analysis identifies leucine-rich repeat insertions crucial for pigeon toll-like receptor 7 recognition and signaling. AB - Toll-like receptor 7 (TLR7) is responsible for recognizing viral single-stranded RNA and antiviral imidazoquinoline compounds, leading to the activation of the innate immune response. In this study, mutated pigeon TLR7 fragments, in which the insertion at position 10 of leucine-rich repeat 10 (LRR10) or at position 15 of LRR2/11/13/14 was deleted, were amplified with an overlap-PCR method, and inserted into the expression vector pCMV. The immune functions of the TLR7 mutants were determined with an NF-kappaB luciferase assay of transfected cells. The deletion of the insertions absolutely abolished TLR7-NF-kappaB signaling. With quantitative real-time PCR and sandwich enzyme-linked immunosorbent assay, we observed that stimulation with R848 failed to induce the expression of interleukin 8 (IL-8) in any of the mutant-TLR7-transfected cells, consistent with their lack of NF-kappaB activity. However, the expression of interferon alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) was significantly upregulated in the Del10IN10 and Del14IN15 groups. Remarkably, the levels of pigeon TLR7 expression were significantly increased in all the TLR7-mutated groups. Therefore, we speculate that another part of the deficient TLR7 mediates the induction of IFN-alpha and TNF-alpha by increasing the expression of TLR7 as compensation. However, the increased expression of TLR7 in the Del11IN15 group failed to induce the production of IFN-alpha, IL-8, or TNF-alpha, indicating that a false compensation occurred when the crucial LRR insertion was deleted. PMID- 26553563 TI - PD-L1 expression is increased in monocyte derived dendritic cells in response to porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus infections. AB - Host immune system suppression is thought to be crucial in the development of porcine circovirus associated diseases (PCVAD). Many immune suppressive mechanisms have been studied in cases of PCVAD, however, the role of programmed death ligand-1 (PD-L1) during porcine circovirus type 2 (PCV2) infection and PCVAD development has yet to be determined. PD-L1 has become an important research target because of its ability to interfere with effective T-cell activity and proliferation during the course of an immune response. In this study, porcine monocyte derived dendritic cells (MoDC) were infected with different combinations of PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV) and evaluated for expression levels of PD-L1, as well as the expression levels of swine major histocompatibility complexes 1 and 2 (SLA-1 and SLA-2) as a measure of MoDC stimulatory capacity. PD-L1 expression levels were also tested in MoDCs after treatment with interferon alpha (IFN-alpha) and beta (IFN-beta). The results showed that the expression levels of PD-L1 were increased in PCV2-infected MoDCs, as well as in PCV2 and PRRSV co-infected MoDCs. The MoDCs infected with PRRSV only also showed a strain-dependent increase in PD-L1 expression. Both IFN-alpha and IFN-beta treatment also increased the expression levels of PD-L1 in MoDCs. SLA-1 and 2 expression levels were increased by PCV2 infection, and altered in the PRRSV, and PCV2+PRRSV co-infected MoDCs in a strain dependent manner. These results indicate a potential immuno-suppressive role for dendritic cells during PCV2 infection and the development of PCVAD and will be helpful in more fully elucidating the underlying mechanisms leading to clinical PCVAD. PMID- 26553564 TI - Natural killer cells in host defense against veterinary pathogens. AB - Natural Killer (NK) cells constitute a major subset of innate lymphoid cells that do not express the T- and B-cell receptors and play an important role in antimicrobial defense. NK cells not only induce early and rapid innate immune responses, but also communicate with dendritic cells to shape the adaptive immunity, thus bridging innate and adaptive immunity. Although the functional biology of NK cells is well-documented in a variety of infections in humans and mice, their role in protecting domestic animals from infectious agents is only beginning to be understood. In this article, we summarize the current state of knowledge about the contribution of NK cells in pathogen defense in domestic animals, especially cattle and pigs. Understanding the immunobiology of NK cells will translate into strategies to manipulate these cells for preventive and therapeutic purposes. PMID- 26553566 TI - Reduced grazing pressure delivers production and environmental benefits for the typical steppe of north China. AB - Degradation by overgrazing is common in many areas of the world and optimising grassland functions depends upon finding suitable grazing tactics. This four-year study on the northern China steppe investigated combinations of rest, moderate or heavy grazing pressure early in the summer growing season, then moderate or heavy grazing in the mid and late season. Results showed that moderate grazing pressure (~550 sheep equivalent (SE) grazing days ha(-1) year(-1)) gave the optimal balance between maintaining a productive and diverse grassland, a profitable livestock system, and greenhouse gas mitigation. Further analyses identified that more conservative stocking (~400 SE grazing days ha(-1) year(-1)) maintained a desirable Leymus chinensis composition and achieved a higher live weight gain of sheep. Early summer rest best maintained a desirable grassland composition, but had few other benefits and reduced incomes. These findings demonstrate that reducing grazing pressure to half the current district stocking rates can deliver improved ecosystem services (lower greenhouse gases and improved grassland composition) while sustaining herder incomes. PMID- 26553567 TI - Purification of binder of sperm protein 1 (BSP1) and its effects on bovine in vitro embryo development after fertilization with ejaculated and epididymal sperm. AB - The present study evaluated functional aspects of binder of sperm 1 (BSP1) in the bovine species. In a first experiment, cumulus-oocyte complexes (n = 1274) were incubated with frozen-thawed ejaculated sperm (18 hours) in Fert-TALP medium containing: heparin, 10, 20, or 40 MUg/mL BSP1. Heparin followed by gelatin affinity chromatography was used for purification of BSP1 from bovine seminal vesicle fluid. With ejaculated sperm, cleavage rates were similar when Fert-TALP medium was incubated with heparin (74.1 +/- 2.7%), 10 MUg/mL BSP1 (77.8 +/- 3.1%), or 20 MUg/mL BSP1 (74 +/- 2.0%). Day-7 blastocyst rates were equivalent after incubations with heparin (40.8 +/- 5.0%) and 10 MUg/mL BSP1 (34.1 +/- 4.4%), but reduced after 20 MUg/mL BSP1 (22.4 +/- 2.9%) and 40 MUg/mL BSP1 (19.3 +/- 4.1%; P < 0.05). In the second experiment, cumulus-oocyte complexes (n = 1213) were incubated with frozen-thawed cauda epididymal sperm (18 hours) in Fert TALP medium containing: no heparin, heparin, 10, 20, or 40 MUg/mL. Cleavage and blastocyst rates were similar after treatments with heparin (68.5 +/- 1.3% and 24.7 +/- 3.2%, respectively) or without heparin (65.5 +/- 1.8% and 27.3 +/- 1.6%, respectively). Cleavage was higher after treatment with any BSP1 concentrations (74.2 +/- 2.7%-79.0 +/- 1.1%) than without heparin (P < 0.05). Also, cleavage was better after Fert-TALP medium incubation with 40 MUg/mL BSP1 (79.0 +/- 1.1%) than with heparin (68.5 +/- 1.3%; P < 0.05). Embryo development was higher (P < 0.05) after treatment with 20 MUg/mL BSP1 (35.6 +/- 2.5%) and 40 MUg/mL (41.1 +/- 2%) than after incubations with heparin (24.7 +/- 3.2%) or without heparin (27.3 +/- 1.6%). Interestingly, BSP1 did not cause reductions in blastocyst rates after fertilization with epididymal sperm, as observed with ejaculated sperm. On the basis of immunocytochemistry, there was BSP1 binding to frozen-thawed ejaculated but not to epididymal sperm. Also, anti-BSP1 reaction remained on ejaculated sperm (as expected) and appeared on epididymal sperm after incubation with purified BSP1. Acrosome reaction of ejaculated and epididymal sperm was induced after incubation with purified BSP1 as well, indicating an effect of BSP1 on capacitation. In conclusion, purified BSP1 from bull seminal vesicles was able to bind to and induce capacitation of ejaculated and epididymal sperm. Also, BSP1 added to fertilization media and allowed proper cleavage and embryo development, with the effects being modulated by previous exposure or not of spermatozoa to seminal plasma. PMID- 26553568 TI - Production of prostaglandins in placentae and corpus luteum in pregnant hinds of red deer (Cervus elaphus). AB - Prostaglandins (PGs) are synthesized from arachidonic acid by prostaglandin synthase 2 (PTGS2) and specific terminal PG synthases such as PGES and PGFS. The role of PGs in the reproductive processes of domestic ruminants is well recognized, whereas in cervidae, it is almost unknown, although it is noteworthy because some species of this family are valued in meat production and trophies. The aim of this study was to determine an effective marker of pregnancy and investigate the production and secretion of PGs in placenta and CL tissue in pregnancy. In the preliminary experiment, the levels of progesterone and 17-beta estradiol (RIA; N = 14 divided into seven pregnant and seven nonpregnant hinds) were measured in the peripheral blood. In the main experiment, a comparison of messenger RNA (real-time polymerase chain reaction) and protein expression (Western blotting) of PTGS2, PGES, and PGFS, the level of prostaglandin E2 (PGE2) and PGF2alpha in the placentae and CL in pregnant hinds (aged 3-4 years, ca. 100 days of pregnancy, N = 6). In pregnant hinds, the level of progesterone in the blood was higher than that in nonpregnant hinds (P < 0.05), whereas the level of E2 was similar in all animals (P > 0.05). The highest messenger RNA expression of PTGS2, PGES, and PGFS was observed in the placentae than in the CL (P < 0.05). The protein expression of PTGS2 and PGES was elevated in the placentae compared with the CL (P < 0.05). The PGE2 output was the highest in cotyledonary tissue (P < 0.05). Pregnancy development in hinds around 100 days is regulated by arachidonic acid metabolites, especially PGE2 produced by the placentae, which production increases in pregnancy. Further studies are required to unravel the mechanisms involved in the regulation of PG and biosynthetic enzymes in uteroplacental and ovarian tissues during pregnancy in red deer females. PMID- 26553569 TI - Effect of vitrification using the Cryotop method on the gene expression profile of in vitro-produced bovine embryos. AB - The present study analyzed the changes in gene expression induced by the Cryotop vitrification technique in bovine blastocyst-stage embryos, using Agilent EmbryoGENE microarray slides. Bovine in vitro-produced embryos were vitrified and compared with nonvitrified (control) embryos. After vitrification, embryos were warmed and cultured for an additional 4 hours. Survived embryos were used for microarray analysis and quantitative polymerase chain reaction (qPCR) quantification. Survival rates were higher (P < 0.05) in the control embryos (100%) than in the vitrified embryos (87%). Global gene expression analysis revealed that only 43 out of 21,139 genes exhibited significantly altered expression in the vitrified embryos compared to the control embryos, with a very limited fold change (P < 0.05). A total of 10 genes were assessed by qPCR. Only the FOS-like antigen 1 (FOSL1) gene presented differential expression (P < 0.05) according to both the array and qPCR methods, and it was overexpressed in vitrified embryos. Although, the major consequence of vitrification seems to be the activation of the apoptosis pathway in some cells. Indeed, FOSL1 is part of the activating protein 1 transcription factor complex and is implicated in a variety of cellular processes, including proliferation, differentiation, and apoptosis. Therefore, our results suggest that a limited increase in the rate of apoptosis was the only detectable response of the embryos to vitrification stress. PMID- 26553571 TI - Rolling Circle Translation of Circular RNA in Living Human Cells. AB - We recently reported that circular RNA is efficiently translated by a rolling circle amplification (RCA) mechanism in a cell-free Escherichia coli translation system. Recent studies have shown that circular RNAs composed of exonic sequences are abundant in human cells. However, whether these circular RNAs can be translated into proteins within cells remains unclear. In this study, we prepared circular RNAs with an infinite open reading frame and tested their translation in eukaryotic systems. Circular RNAs were translated into long proteins in rabbit reticulocyte lysate in the absence of any particular element for internal ribosome entry, a poly-A tail, or a cap structure. The translation systems in eukaryote can accept much simpler RNA as a template for protein synthesis by cyclisation. Here, we demonstrated that the circular RNA is efficiently translated in living human cells to produce abundant protein product by RCA mechanism. These findings suggest that translation of exonic circular RNAs present in human cells is more probable than previously thought. PMID- 26553572 TI - A rigid lanthanide binding tag to aid NMR studies of a 70 kDa homodimeric coat protein of human norovirus. AB - Attachment of human noroviruses to histo blood group antigens is thought to be essential for infection of host cells. Molecular details of the attachment process can be studied in vitro using a variety of NMR experiments. The use of protein NMR based experiments requires assignments of backbone NMR signals. Using uniformly (2)H,(15)N-labeled protruding domains (P-dimers) of a prevalent epidemic human norovirus strain (GII.4 Saga) we have studied the potential of alpha-l-fucose covalently linked to a rigid lanthanide binding tag to aid backbone assignments using the paramagnetic properties of lanthanide ions. The synthesis of tagged alpha-l-fucose is reported. Notably, the metal chelating unit connects to the carbohydrate via a triazole linker constructed using click chemistry. PMID- 26553573 TI - [Functional performance of school children diagnosed with developmental delay up to two years of age]. AB - OBJECTIVE: To compare the functional performance of students diagnosed with developmental delay (DD) up to two years of age with peers exhibiting typical development. METHODS: Cross-sectional study with functional performance assessment of children diagnosed with DD up to two years of age compared to those with typical development at seven to eight years of age. Each group consisted of 45 children, selected by non-random sampling, evaluated for motor skills, quality of home environment, school participation and performance. ANOVA and the Binomial test for two proportions were used to assess differences between groups. RESULTS: The group with DD had lower motor skills when compared to the typical group. While 66.7% of children in the typical group showed adequate school participation, receiving aid in cognitive and behavioral tasks similar to that offered to other children at the same level, only 22.2% of children with DD showed the same performance. Although 53.3% of the children with DD achieved an academic performance expected for the school level, there were limitations in some activities. Only two indicators of family environment, diversity and activities with parents at home, showed statistically significant difference between the groups, with advantage being shown for the typical group. CONCLUSIONS: Children with DD have persistent difficulties at school age, with motor deficit, restrictions in school activity performance and low participation in the school context, as well as significantly lower functional performance when compared to children without DD. A systematic monitoring of this population is recommended to identify needs and minimize future problems. PMID- 26553574 TI - [Characterization of anthropometric assessment studies of Brazilian children attending daycare centers]. AB - OBJECTIVE: To obatin an overview of available information on the anthropometric assessment of Brazilian children attending daycare centers. DATA SOURCE: A literature search was carried out in the PubMed, LILACS and SciELO databases of studies published from 1990 to 2013 in Portuguese and English languages. The following search strategy was used: (nutritional status OR anthropometrics OR malnutrition OR overweight) AND daycare centers, as well as the equivalent terms in Portuguese. In the case of MEDLINE search, the descriptor Brazil was also used. DATA SYNTHESIS: It was verified that the 33 studies included in the review were comparable from a methodological point of view. The studies, in general, were characterized by their restrictive nature, geographical concentration and dispersion of results in relation to time. Considering the studies published from 2010 onwards, low prevalence of acute malnutrition and significant rates of stunting and overweight were observed. CONCLUSIONS: Despite the limitations, considering the most recent studies that used the WHO growth curves (2006), it is suggested that the anthropometric profile of Brazilian children attending daycare centers is characterized by a nutritional transition process, with significant prevalence of overweight and short stature. We emphasize the need to develop a multicenter survey that will more accurately define the current anthropometric nutritional status of Brazilian children attending daycare centers. PMID- 26553576 TI - Optical absorption characteristics in the assessment of powder phosphor-based x ray detectors: from nano- to micro-scale. AB - X-ray phosphor-based detectors have enormously improved the quality of medical imaging examinations through the optimization of optical diffusion. In recent years, with the development of science and technology in the field of materials, improved powder phosphors require structural and optical properties that contribute to better optical signal propagation. The purpose of this paper was to provide a quantitative and qualitative understanding of the optical absorption characteristics in the assessment of powder phosphor-based detectors (from nano- scale up to micro-scale). Variations on the optical absorption parameters (i.e. the light extinction coefficient [Formula: see text] and the percentage probability of light absorption p%) were evaluated based on Mie calculations examining a wide range of light wavelengths, particle refractive indices and sizes. To model and assess the effects of the aforementioned parameters on optical diffusion, Monte Carlo simulation techniques were employed considering: (i) phosphors of different layer thickness, 100 MUm (thin layer) and 300 MUm (thick layer), respectively, (ii) light extinction coefficient values, 1, 3 and 6 MUm(-1), and (iii) percentage probability of light absorption p% in the range 10( 4)-10(-2). Results showed that the [Formula: see text] coefficient is high for phosphor grains in the submicron scale and for low light wavelengths. At higher wavelengths (above 650 nm), optical quanta follow approximately similar depths until interaction for grain diameter 500 nm and 1 MUm. Regarding the variability of the refractive index, high variations of the [Formula: see text] coefficient occurred above 1.6. Furthermore, results derived from Monte Carlo modeling showed that high spatial resolution phosphors can be accomplished by increasing the [Formula: see text] parameter. More specifically, the FWHM was found to decrease (i.e. higher resolution): (i) 4.8% at 100 MUm and (ii) 9.5%, at 300 MUm layer thickness. This study attempted to examine the role of the optical absorption parameters on optical diffusion studies. A significant outcome of the present investigation was that the improvement of phosphor spatial resolution without decreasing the light collection efficiency too much can be better achieved by increasing the parameter [Formula: see text] rather than the parameter p%. PMID- 26553575 TI - Novel Method to Track Soft Tissue Deformation by Micro-Computed Tomography: Application to the Mitral Valve. AB - Increasing availability of micro-computed tomography (uCT) as a structural imaging gold-standard is bringing unprecedented geometric detail to soft tissue modeling. However, the utility of these advances is severely hindered without analogous enhancement to the associated kinematic detail. To this end, labeling and following discrete points on a tissue across various deformation states is a well-established approach. Still, existing techniques suffer limitations when applied to complex geometries and large deformations and strains. Therefore, we herein developed a non-destructive system for applying fiducial markers (minimum diameter: 500 um) to soft tissue and tracking them through multiple loading conditions by uCT. Using a novel applicator to minimize adhesive usage, four distinct marker materials were resolvable from both tissue and one another, without image artifacts. No impact on tissue stiffness was observed. uCT addressed accuracy limitations of stereophotogrammetry (inter-method positional error 1.2 +/- 0.3 mm, given marker diameter 1.9 +/- 0.1 mm). Marker application to ovine mitral valves revealed leaflet Almansi areal strains (45 +/- 4%) closely matching literature values, and provided radiographic access to previously inaccessible regions, such as the leaflet coaptation zone. This system may meaningfully support mechanical characterization of numerous tissues or biomaterials, as well as tissue-device interaction studies for regulatory standards purposes. PMID- 26553577 TI - New variational image decomposition model for simultaneously denoising and segmenting optical coherence tomography images. AB - Optical coherence tomography (OCT) imaging plays an important role in clinical diagnosis and monitoring of diseases of the human retina. Automated analysis of optical coherence tomography images is a challenging task as the images are inherently noisy. In this paper, a novel variational image decomposition model is proposed to decompose an OCT image into three components: the first component is the original image but with the noise completely removed; the second contains the set of edges representing the retinal layer boundaries present in the image; and the third is an image of noise, or in image decomposition terms, the texture, or oscillatory patterns of the original image. In addition, a fast Fourier transform based split Bregman algorithm is developed to improve computational efficiency of solving the proposed model. Extensive experiments are conducted on both synthesised and real OCT images to demonstrate that the proposed model outperforms the state-of-the-art speckle noise reduction methods and leads to accurate retinal layer segmentation. PMID- 26553578 TI - Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer. AB - BACKGROUND: The treatment of patients with metastatic colorectal cancer (mCRC) has evolved during the past 2 decades, and patient survival has increased. Consequently, patients are exposed to more chemotherapeutic agents and regimens. Little is known about therapeutic drug sequencing and the factors influencing these choices. MATERIALS AND METHODS: An observational, retrospective medical record review was conducted of patients with newly diagnosed adult mCRC from January 2002 to September 2013 identified in the McGill University-Jewish General Hospital's local tumor registry. All patients presented with mCRC (stage IV) and received >= 2 cycles and/or >= 28 days of first-line chemotherapy. The patient demographics, CRC characteristics, treatment patterns, and outcomes were recorded. The reason for changing or halting therapy was also reported. RESULTS: Of the 215 patients who underwent treatment, 74.4% received second-line, 36% third-line, and 16.3% fourth-line treatment. In total, 88% received >= 3 classes of cytotoxic chemotherapy and 80% received >= 1 biologic agent. The most common first-line treatment was FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) (47.4%) or CAPOX (capecitabine, oxaliplatin) (28.8%), and more than one half received bevacizumab (56%). Among the second- and third-line treatments, FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) was the most common (40.3% and 30.3%, respectively), and bevacizumab was the most frequently used biologic agent (48.1% and 39.2%, respectively). For fourth-line treatment and beyond, most patients participated in clinical trials (45.7%) or received panitumumab monotherapy (31.4%). Across the first 4 therapy lines, disease progression was the primary motive for discontinuation (39.5%, 53.8%, 58.2%, and 37.1%). CONCLUSION: FOLFOX was the most common first-line and FOLFIRI the most common second- and third-line mCRC therapy. Bevacizumab was the most frequently used targeted therapy across all 3 treatment lines. Therapy discontinuation was primarily due to disease progression. PMID- 26553579 TI - Changes in brain functional connectivity patterns are driven by an individual lesion in MS: a resting-state fMRI study. AB - Diffuse inflammation in multiple sclerosis (MS) extends beyond focal lesion sites, affecting interconnected regions; however, little is known about the impact of an individual lesion affecting major white matter (WM) pathways on brain functional connectivity (FC). Here, we longitudinally assessed the effects of acute and chronic lesions on FC in relapsing-remitting MS (RRMS) patients using resting-state fMRI. 45 MRI data sets from 9 RRMS patients were recorded using 3T MR scanner over 5 time points at 8 week intervals. Patients were divided into two groups based on the presence (n = 5; MS+) and absence (n = 4; MS-) of a lesion at a predilection site for MS. While FC levels were found not to fluctuate significantly in the overall patient group, the MS+ patient group showed increased FC in the contralateral cuneus and precuneus and in the ipsilateral precuneus (p < 0.01, corrected). This can be interpreted as the recruitment of intact cortical regions to compensate for tissue damage. During the study, one patient developed an acute WM lesion in the left posterior periventricular space. A marked increase in FC in the right pre-, post-central gyrus, right superior frontal gyrus, the left cuneus, the vermis and the posterior and anterior lobes of the cerebellum was noted following the clinical relapse, which gradually decreased in subsequent follow-ups, suggesting short-term functional reorganization during the acute phase. This strongly suggests that the lesion related network changes observed in patients with chronic lesions occur as a result of reorganization processes following the initial appearance of an acute lesion. PMID- 26553580 TI - The reliability of individual differences in face-selective responses in the fusiform gyrus and their relation to face recognition ability. AB - Face recognition ability varies widely in the normal population and there is increasing interest in linking individual differences in perception to their neural correlates. Such brain-behavior correlations require that both the behavioral measures and the selective BOLD responses be reliable. The reliability of the location of the fusiform face area (FFA) has been demonstrated in several studies. Here, we address reliability of a different kind: reliability of the magnitude of responses to faces within this localized region. We calculated split half reliability of face-selective responses within functionally defined posterior and anterior face-selective patches in the fusiform gyrus (FFA1/FFA2). We used data from two published studies that included both a functional localizer for face-selective regions and independent data suitable for quantifying face selectivity. We found highly reliable face selectivity in both hemispheres that was highest in the centermost voxel(s) compared to larger regions of interest. Differences in face-selectivity between the two face patches within one hemisphere and across hemispheres were also reliable. Our results reveal considerable reliability of face-selective signals in and across FFA in adults. Given the good reliability of behavioral measures of face recognition, prior failures to find a relationship between the mean response to faces in FFA and behavioral face recognition in normal adult subjects are unlikely to be due to limitations of the measurements. PMID- 26553581 TI - Color Tuning of Core-Shell Fluorescent Microspheres by Controlling the Conjugation of Poly(p-phenylenevinylene) Backbone. AB - A series of poly(p-phenylenevinylene) (PPV)-coated microspheres with varied fluorescent emission colors have been prepared by controlling the average length of the conjugated segments on the polymer backbone. A modified Wessling method was used for preparing PPV with different conjugation segments. The labile sulfonium groups of the initial polymer precursor of PPV (pre-PPV) were partly substituted by relatively stable methoxyl groups. A series of precursors with different degrees of substitution were prepared by controlling the time of reaction; these precursors were adsorbed onto the negatively charged substrate spheres. Subsequently, heterogeneous thermal treatment eliminated the sulfonium groups selectively to form the conjugated segments on the PPV backbone with varied average conjugation lengths. Under UV exposure, the as-prepared PPV-coated microspheres displayed emission colors ranging from blue to green; a 65 nm shift in the emission maximum was observed in the fluorescence spectra. The gradual color change in emission of spheres was also confirmed in a confocal microscopy study. Further characterizations indicated that these microspheres possessed clear core-shell structure, good monodispersity in size, smooth surfaces, uniform emission, and superior thermal and photo stability. Flow cytometry measurements indicated that these spheres have very different patterns of intensity combination from four-signal receiving channels. The simple method reported herein, which can effectively and efficiently tune the emission color of the fluorescent microspheres, is a promising approach for preparation of microspheres used as encoded signal carrier in flow cytometry and other high-throughput techniques. PMID- 26553582 TI - Job Crafting in the Time of Imaging 3.0. PMID- 26553583 TI - Modifying Thermal Transport in Colloidal Nanocrystal Solids with Surface Chemistry. AB - We present a systematic study on the effect of surface chemistry on thermal transport in colloidal nanocrystal (NC) solids. Using PbS NCs as a model system, we vary ligand binding group (thiol, amine, and atomic halides), ligand length (ethanedithiol, butanedithiol, hexanedithiol, and octanedithiol), and NC diameter (3.3-8.2 nm). Our experiments reveal several findings: (i) The ligand choice can vary the NC solid thermal conductivity by up to a factor of 2.5. (ii) The ligand binding strength to the NC core does not significantly impact thermal conductivity. (iii) Reducing the ligand length can decrease the interparticle distance, which increases thermal conductivity. (iv) Increasing the NC diameter increases thermal conductivity. (v) The effect of surface chemistry can exceed the effect of NC diameter and becomes more pronounced as NC diameter decreases. By combining these trends, we demonstrate that the thermal conductivity of NC solids can be varied by an overall factor of 4, from ~0.1-0.4 W/m-K. We complement these findings with effective medium approximation modeling and identify thermal transport in the ligand matrix as the rate-limiter for thermal transport. By combining these modeling results with our experimental observations, we conclude that future efforts to increase thermal conductivity in NC solids should focus on the ligand-ligand interface between neighboring NCs. PMID- 26553584 TI - A simple synthesis of urchin-like Pt-Ni bimetallic nanostructures as enhanced electrocatalysts for the oxygen reduction reaction. AB - The synthesis of urchin-like Pt-Ni bimetallic nanostructures is achieved by a controlled one-pot synthesis. Pt-Ni nanostructures have superior oxygen reduction reaction activities in both with and without specific anion adsorption electrolytes due to the geometric and alloying effects. PMID- 26553585 TI - Patient characteristics affecting stroke identification by emergency medical service providers in Brooklyn, New York. AB - Early identification of stroke should begin in the prehospital phase because the benefits of thrombolysis and clot extraction are time dependent. This study aims to identify patient characteristics that affect prehospital identification of stroke by Long Island college hospital (LICH) emergency medical services (EMS). All suspected strokes brought to LICH by LICH ambulances from January 1, 2010 to December 31, 2011 were included in the study. We compared prehospital care report based diagnosis against the get with the guidelines (GWTG) database. Age-adjusted logistic regression models were used to study that the effect of individual patient characteristics have on EMS providers' diagnosis. Included in the study were 10,384 patients with mean age 43.9 years. Of whom, 75 had a GWTG cerebrovascular diagnosis: 53 were ischemic strokes, 7 transient ischemic attacks, 3 subarachnoid hemorrhage, and 12 intercerebral bleeds. LICH EMS correctly identified 44 of 75 GWTG strokes. Fifty-one patients were overcalled as stroke by the EMS. Overall EMS sensitivity was 58.7 % and specificity was 99.5 %. Dispatcher call type of altered mental status, stroke, unconsciousness, and increasing prehospital blood pressure quartile were found to be significantly predictive of a true stroke diagnosis. Patients with a past medical history and EMS providers' impression of seizures were more likely to be overcalled as a stroke in the field. More than a third of actual stroke patients were missed in the field in our study. Our results show that the patients' past medical history, dispatcher collected information and prehospital vital sign measurements are associated with a true diagnosis of stroke. PMID- 26553586 TI - Beating Diabetes Together: A Mixed-Methods Analysis of a Feasibility Study of Intensive Lifestyle Intervention for Youth with Type 2 Diabetes. AB - OBJECTIVES: The purpose of this study was to assess the feasibility and lived experiences of an intensive group-based lifestyle intervention for youth with type 2 diabetes (Beating Diabetes Together) (BDT). METHODS: The study included 12 Indigenous youth with type 2 diabetes (mean age, 14 years; n=9 girls); they participated in a 16-week pilot study of an intensive, group-based lifestyle intervention. We conducted a mixed-methods investigation of the cardiometabolic responses and lived experiences in the intervention. Of the 12 youth with cardiometabolic risk data, 5 youth and 2 mothers participated in semistructured interviews. Interview participants were purposely selected based on the frequency of attendance and availability. RESULTS: The intervention was well attended (>75% retention), and youth perceived significant benefits from participation. Thematic analysis of the interviews revealed 3 major themes. First, youth and parents described living with type 2 diabetes as being emotionally challenging. They described this experience as being isolating and connected to feelings of guilt and defeat. Second, youth and parents discussed benefits of participating in BDT. They shared the significance of positive relationships and experiences and how those have helped to manage their illness. Third, youth described the aspects that they most enjoyed at BDT. Peer support was an important determinant of physical activity, but they considered dietary changes to be individual behaviours. Glycemic control, blood pressure and anthropometric measures were not different following the intervention. CONCLUSIONS: Our findings support the importance of maintaining an inclusive environment and relationship building when designing strategies to promote behaviour modification for Indigenous youth living with type 2 diabetes. PMID- 26553587 TI - Arjunolic acid protects against DNCB-induced atopic dermatitis-like symptoms in mice by restoring a normal cytokine balance. AB - PURPOSE: Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. The effect of oral arjunolic acid (AA) on 2,4 dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice was investigated. METHODS: Repeated epicutaneous application of DNCB to the ear and shaved dorsal skin of mice was performed to induce AD-like symptoms and skin lesions: 250mg/kg AA was given orally for three weeks to assess its anti-pruritic effects. Serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-6, IL-10, immunoglobulin (Ig)E and caspase-3 were assessed by ELISA. RESULTS: We found that AA alleviated DNCB-induced AD-like symptoms as quantified by skin lesions, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the AA group were significantly inhibited compared with those in the DNCB group. In parallel, AA blocked a DNCB-induced reduction in serum levels of IL-4 and IL-10 associated with an attenuation of DNCB-induced increases in serum TNF-alpha, IL-6, IgE and caspase-3. CONCLUSIONS: The results indicate that AA suppresses DNCB-induced AD in mice via redox balance and immune modulation, and could be a safe clinical treatment for AD. PMID- 26553588 TI - Evaluation of two different adjuvants with immunogenic uroplakin 3A-derived peptide for their ability to evoke an immune response in mice. AB - RATIONALE: Organ- or tissue-specific antigens produced by normal tissue or by cancer cells could be used in cancer immunotherapy, to target the tumor. In our previous study, we induced T-cell-mediated, bladder-specific autoimmunity by targeting the bladder-specific protein Uroplakin 3A (UPK3A). UPK3A is a well chosen target for developing an autoimmune response against bladder cancer since the antigen is also expressed in bladder tumors. To use this peptide, which was derived from the UPK3A protein in a bladder cancer vaccine study, it is necessary to induce a strong immune response. In this study, we aimed to develop a robust immune response in BALB/c mice using the well-characterized keyhole limpet hemocyanin (KLH)-conjugated peptide antigen (UPK3A 65-84) conjugated with an immunogenic carrier protein. In combination with the peptide, we used either Freund's complete adjuvant (CFA) or CpG (cytosine-phosphate-guanine oligonucleotides) as effective adjuvants in order to overcome tumor tolerance. OBJECTIVES: The immune response evoked by UPK3A 65-84 peptide, using two different adjuvants, was compared by detection of changes in the proliferative response of immune cells, in the cytokine profile, and in the immune cell populations. FINDINGS: We demonstrated that CpG, combined with KLH-UPK3A 65-84, promoted a more robust immune response, via induction of higher IL-2, IFN-gamma, TNF-alpha, IL-17 production and activation of more immune cells (CD4(+) T cells, CD8(+) T cells, NK cells CD11b, CD45), than CFA and the KLH- UPK3A 65-84. CONCLUSION: CpG as an adjuvant combined with KLH-UPK3A 65-84 could be used in preclinical models of bladder cancer for the development of cancer immunotherapy strategies. PMID- 26553589 TI - Photoluminescence Spectroscopy of Mass-Selected Electrosprayed Ions Embedded in Cryogenic Rare-Gas Matrixes. AB - An apparatus is presented which combines nanoelectrospray ionization for isolation of large molecular ions from solution, mass-to-charge ratio selection in gas-phase, low-energy-ion-beam deposition into a (co-condensed) inert gas matrix and UV laser-induced visible-region photoluminescence (PL) of the matrix isolated ions. Performance is tested by depositing three different types of lanthanoid diketonate cations including also a dissociation product species not directly accessible by chemical synthesis. For these strongly photoluminescent ions, accumulation of some femto- to picomoles in a neon matrix (over a time scale of tens of minutes to several hours) is sufficient to obtain well-resolved dispersed emission spectra. We have ruled out contributions to these spectra due to charge neutralization or fragmentation during deposition by also acquiring photoluminescence spectra of the same ionic species in the gas phase. PMID- 26553590 TI - Templation of a square grid copper(II) 4,4'-bipyridine network by a 3D PtS related Cu(I)-Cu(II) 4,4'-bipyridine crystal. AB - Two cationic networks, [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) and [Cu(II)(4,4'bipy)2(H2O)2](2+) have been formed from a solution in which Cu(I) undergoes aerial oxidation. Whilst the topologies of the two networks are different the arrangement of Cu centres is almost identical, a structural feature which presumably allows for [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) to serve as a crystalline template for [Cu(II)(bipy)2(H2O)2](2+). PMID- 26553591 TI - Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice. AB - Mesenchymal stem cells (MSCs) are an attractive cell source for cell therapy. Based on our hypothesis that suppression of Wnt/beta-catenin signal enhances hepatic differentiation of human MSCs, we developed human mesenchymal stem cell engineered hepatic cell sheets by a small molecule compound. Screening of 10 small molecule compounds was performed by WST assay, TCF reporter assay, and albumin mRNA expression. Consequently, hexachlorophene suppressed TCF reporter activity in time- and concentration-dependent manner. Hexachlorophene rapidly induced hepatic differentiation of human MSCs judging from expression of liver specific genes and proteins, PAS staining, and urea production. The effect of orthotopic transplantation of human mesenchymal stem cell-engineered hepatic cell sheets against acute liver injury was examined in one-layered to three-layered cell sheets system. Transplantation of human mesenchymal stem cell-engineered hepatic cell sheets enhanced liver regeneration and suppressed liver injury. The survival rates of the mice were significantly improved. High expression of complement C3 and its downstream signals including C5a, NF-kappaB, and IL-6/STAT 3 pathway was observed in hepatic cell sheets-grafted tissues. Expression of phosphorylated EGFR and thioredoxin is enhanced, resulting in reduction of oxidative stress. These findings suggest that orthotopic transplantation of hepatic cell sheets manufactured from MSCs accelerates liver regeneration through complement C3, EGFR and thioredoxin. PMID- 26553593 TI - Alzheimer disease: Alzheimer dementia with sparse amyloid-AD mimic or variant? PMID- 26553592 TI - MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation. AB - The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53(+/+) and TP53(-/-) HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT. PMID- 26553595 TI - A Patient Portal With Electronic Messaging: Controlled Before-and-After Study. AB - BACKGROUND: Patients' access to their medical records, along with electronic messaging, offers an efficient means of information transition between patients and their caregivers. Easier access to information and interaction with health care professionals may reduce use of other services while increasing patients' activation in the management of their own health. Patient portals may therefore have a favorable impact on the cost-effectiveness of care. OBJECTIVE: The aim was to assess the benefits and risks of providing electronic messaging services to patients with chronic conditions. Using cost-effectiveness analysis, the outcomes and costs of providing access to an electronic patient portal were evaluated in a real-life treatment process in primary care. METHODS: A total of 876 chronically ill patients from public primary care were allocated to either an intervention group receiving immediate access to a patient portal that included their medical records, care plan, and secure messaging with a care team, or to a control group receiving standard care. Incremental direct heath care costs, health status based on the Short-Form Health Survey, version 2 (SF-36v2), and patient activation based on the short form of the Patient Activation Measure (PAM13) were compared to standard care in a 6-month follow-up. Incremental cost-effectiveness ratios were calculated using a sample of 80 patients in the intervention group and 57 patients in the control group; thus, a total of 137 patients were included in the final analysis. Propensity-score matching was used to assess the sensitivity of the results to the possible attrition bias. RESULTS: Patient activation improved more in the intervention group but the effect was not statistically significant. The effect on cost of care was ambiguous; costs decreased by an average of ?91 in the unadjusted model, but increased by ?48 in the adjusted model. Due to the controversial results on cost, the unadjusted analysis showed an 89% probability of cost-effectiveness with no willingness to pay for increased patient activation, whereas in the adjusted sample, the probability of the portal being more cost-effective than care as usual exceeded 50% probability at a willingness to pay ?700 per clinically significant increase in patient activation score. There was no marked short-term impact on health status based on the SF-36v2 measure. CONCLUSIONS: Offering the possibility to substitute health care visits with less costly contacts using self-management tools did not seem to compromise the health status or treatment of chronic care patients. Patient activation increased, and this could be achieved with moderate costs in a short-term experiment. In the long term, increased activation is proposed to lead to better health outcomes and eventually cut down resource use. Future studies should assess the long-term effects of patient portals on patients' health status and cost of care. PMID- 26553594 TI - A novel diagnostic approach to patients with myoclonus. AB - Myoclonus is a hyperkinetic movement disorder characterized by brief, involuntary muscular jerks. Recognition of myoclonus and determination of the underlying aetiology remains challenging given that both acquired and genetically determined disorders have varied manifestations. The diagnostic work-up in myoclonus is often time-consuming and costly, and a definitive diagnosis is reached in only a minority of patients. On the basis of a systematic literature review up to June 2015, we propose a novel diagnostic eight-step algorithm to help clinicians accurately, efficiently and cost-effectively diagnose myoclonus. The large number of genes implicated in myoclonus and the wide clinical variation of these genetic disorders emphasize the need for novel diagnostic techniques. Therefore, and for the first time, we incorporate next-generation sequencing (NGS) in a diagnostic algorithm for myoclonus. The initial step of the algorithm is to confirm whether the movement disorder phenotype is consistent with, myoclonus, and to define its anatomical subtype. The next steps are aimed at identification of both treatable acquired causes and those genetic causes of myoclonus that require a diagnostic approach other than NGS. Finally, other genetic diseases that could cause myoclonus can be investigated simultaneously by NGS techniques. To facilitate NGS diagnostics, we provide a comprehensive list of genes associated with myoclonus. PMID- 26553596 TI - Amyloid-beta adopts a conserved, partially folded structure upon binding to zwitterionic lipid bilayers prior to amyloid formation. AB - Aggregation at the neuronal cell membrane's lipid bilayer surface is implicated in amyloid-beta (Abeta) toxicity associated with Alzheimer's disease; however, structural and mechanistic insights into the process remain scarce. We have identified a conserved binding mode of Abeta40 on lipid bilayer surfaces with a conserved helix containing the self-recognition site (K16-E22). PMID- 26553598 TI - From the Editor. PMID- 26553599 TI - Outstanding translational science at American Society of Hypertension 2015. PMID- 26553597 TI - Ventral tegmental area dopamine and GABA neurons: Physiological properties and expression of mRNA for endocannabinoid biosynthetic elements. AB - The ventral tegmental area (VTA) is involved in adaptive reward and motivation processing and is composed of dopamine (DA) and GABA neurons. Defining the elements regulating activity and synaptic plasticity of these cells is critical to understanding mechanisms of reward and addiction. While endocannabinoids (eCBs) that potentially contribute to addiction are known to be involved in synaptic plasticity mechanisms in the VTA, where they are produced is poorly understood. In this study, DA and GABAergic cells were identified using electrophysiology, cellular markers, and a transgenic mouse model that specifically labels GABA cells. Using single-cell RT-qPCR and immunohistochemistry, we investigated mRNA and proteins involved in eCB signaling such as diacylglycerol lipase alpha, N-acyl-phosphatidylethanolamine-specific phospholipase D, and 12-lipoxygenase, as well as type I metabotropic glutamate receptors (mGluRs). Our results demonstrate the first molecular evidence of colocalization of eCB biosynthetic enzyme and type I mGluR mRNA in VTA neurons. Further, these data reveal higher expression of mGluR1 in DA neurons, suggesting potential differences in eCB synthesis between DA and GABA neurons. These data collectively suggest that VTA GABAergic and DAergic cells have the potential to produce various eCBs implicated in altering neuronal activity or plasticity in adaptive motivational reward or addiction. PMID- 26553600 TI - ASH 2015 Annual Primary Care Program: What you missed by not attending. PMID- 26553602 TI - Autoimmunity: Ro60-associated RNA takes its toll on disease pathogenesis. PMID- 26553605 TI - Rheumatoid arthritis: Novel NFkappaB inhibitor associated with RA severity. PMID- 26553601 TI - Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis. AB - Silica dust mainly attacks alveolar macrophages (AMs) and increases the apoptosis of AMs in silicosis patients. However, it is still unclear whether autophagy is affected. Autophagy mainly has defensive functions in response to stress, contributing to cell survival in adverse conditions, and conversely it has also been implicated in cell death. Lipopolysaccharide (LPS) induces autophagy and apoptosis in macrophages. The role of LPS in autophagy and apoptosis in AMs of silicosis patients is unknown. In this study, we collected AMs from 53 male workers exposed to silica and divided them into an observer (control) group, and stage I, II and III patient groups. We found increased levels of LC3B, SQSTM1/p62 and BECN1,whereas the phosphorylation of MTOR,and levels of LAMP2, TLR4, MYD88, TICAM1, as well as the number of lysosomes decreased with the development of silicosis. LPS stimulation triggered autophagy and increased levels of SQSTM1 in AMs. The autophagy inhibitor, 3-methyladenine (3MA), inhibited LPS-induced apoptosis in the AMs of silicosis patients. Moreover, 3MA reversed the LPS induced decrease in BCL2 and the increase in BAX and CASP3 levels in AMs. These results suggest that autophagosomes accumulate in AMs during silicosis progression. LPS can induce the formation of autophagosomes through a TLR4 dependent pathway, and LPS may exacerbate the apoptosis in AMs. Blockade of the formation of autophagosomes may inhibit LPS-induced apoptosis via the intrinsic apoptotic pathway in AMs. These findings describe novel mechanisms that may lead to new preventive and therapeutic strategies for pulmonary fibrosis. PMID- 26553608 TI - Mitochondrial phenotype of marsupial torpor: Fuel metabolic switch in the Chilean mouse-opossum Thylamys elegans. AB - Torpor is a phenotype characterized by a controlled decline of metabolic rate and body temperature. During arousal from torpor, organs undergo rapid metabolic reactivation and rewarming to near normal levels. As torpor progress, animals show a preference for fatty acids over glucose as primary source of energy. Here, we analyzed for first time the changes in the maximal activity of key enzymes related to fatty acid (Carnitine palmitoyltransferase and beta-Hydroxyacyl CoA dehydrogenase) and carbohydrate (Pyruvate kinase, Phosphofructokinase and Lactate dehydrogenase) catabolism, as well as mitochondrial oxidative capacity (Citrate synthase), in six organs of torpid, arousing and euthermic Chilean mouse-opossums (Thylamys elegans). Our results showed that activity of enzymes related to fatty acid and carbohydrate catabolism were different among torpor phases and the pattern of variation differs among tissues. In terms of lipid utilization, maximal enzymatic activities differ in tissues with high oxidative capacity such as heart, kidney, and liver. In terms of carbohydrate use, lower enzymatic activities were observed during torpor in brain and liver. Interestingly, citrate synthase activity did not differ thought torpor-arousal cycle in any tissues analyzed, suggesting no modulation of mitochondrial content in T. elegans. Overall results provide an indication that modulation of enzymes associated with carbohydrate and fatty-acid pathways is mainly oriented to limit energy expensive processes and sustain energy metabolism during transition from torpor to euthermy. Future studies are required to elucidate if physiological events observed for T. elegans are unique from other marsupials, or represents a general response in marsupials. J. Exp. Zool. 325A:41-51, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26553609 TI - Surface ligand-directed pair-wise hydrogenation for heterogeneous phase hyperpolarization. AB - para-Hydrogen induced polarization is a technique of magnetic resonance hyperpolarization utilizing hydrogen's para-spin state for generating signal intensities at magnitudes far greater than state-of-the-art magnets. Platinum nanoparticle-catalysts with cysteine-capping are presented. The measured polarization is the highest reported to date in water, paving pathways for generating medical imaging contrast agents. PMID- 26553610 TI - Methane excess in Arctic surface water-triggered by sea ice formation and melting. AB - Arctic amplification of global warming has led to increased summer sea ice retreat, which influences gas exchange between the Arctic Ocean and the atmosphere where sea ice previously acted as a physical barrier. Indeed, recently observed enhanced atmospheric methane concentrations in Arctic regions with fractional sea-ice cover point to unexpected feedbacks in cycling of methane. We report on methane excess in sea ice-influenced water masses in the interior Arctic Ocean and provide evidence that sea ice is a potential source. We show that methane release from sea ice into the ocean occurs via brine drainage during freezing and melting i.e. in winter and spring. In summer under a fractional sea ice cover, reduced turbulence restricts gas transfer, then seawater acts as buffer in which methane remains entrained. However, in autumn and winter surface convection initiates pronounced efflux of methane from the ice covered ocean to the atmosphere. Our results demonstrate that sea ice-sourced methane cycles seasonally between sea ice, sea-ice-influenced seawater and the atmosphere, while the deeper ocean remains decoupled. Freshening due to summer sea ice retreat will enhance this decoupling, which restricts the capacity of the deeper Arctic Ocean to act as a sink for this greenhouse gas. PMID- 26553612 TI - Serological IgE Analyses in the Diagnostic Algorithm for Allergic Disease. AB - IgE antibody analyses using serological methods are an integral part of the diagnostic evaluation of a patient for allergic disease. They serve to clarify whether a state of sensitization exists in the patient as one of the many risk factors for elicitation of allergic symptoms. This overview examines the role that IgE antibody measurements play in the diagnostic algorithm when considering the pretest likelihood of disease on the basis of the patient's clinical history. Each of the 4 allergen groups (inhalants, venoms, drugs, and foods) are discussed in the context of the various in vitro and in vivo modalities for evaluating sensitization to allergens. Both the past and present analytical methods for IgE antibody detection and quantification in serum are critiqued. Causes for discordant IgE antibody levels with allergy symptoms are discussed with a special focus on analytically valid but clinically irrelevant positive IgE responses. Finally, applications are discussed where allergenic molecules provide enhanced analytical and diagnostic sensitivity and specificity when compared with results generated with allergen extract-based IgE assays. PMID- 26553611 TI - Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites. AB - Metastatic colorectal cancer (mCRC) carries a poor prognosis with an overall 5 year survival of 13.1%. Therapies guided by tumor profiling have suggested benefit in advanced cancer. We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n = 1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low RRM1 (57%), TS (71%) and MGMT (39%), suggesting possible benefit from irinotecan, gemcitabine, 5FU/capecitabine and temozolomide, respectively. Lung metastases harbored a higher Her2 protein expression than the primary colon tumors (4% vs. 1.8%, p = 0.028). Brain and lung metastases had higher KRAS mutations than other sites (65% vs 59% vs 47%, respectively, p = 0.07, <0.01), suggesting poor response to anti-EGFR therapies. BRAF-mutated CRC (n = 455) showed coincident high protein expression of RRM1 (56%), TS (53%) and low PDGFR (22%) as compared with BRAF wild-type tumors. KRAS-mutated mCRC had higher protein expression of c-MET (47% vs. 36%) and lower MGMT (56% vs. 63%), suggesting consideration of c-MET inhibitors and temozolomide. KRAS-mutated CRC had high TUBB3 (42% vs. 33%) and low Her2 by IHC (0.5%) and HER2 by FISH (3%, p <0.05). CRC primaries had a lower incidence of PIK3CA and BRAF mutations in rectal cancer versus colon cancer (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among BRAF/KRAS sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP. PMID- 26553613 TI - Molecular Allergen-Specific IgE Assays as a Complement to Allergen Extract-Based Sensitization Assessment. AB - Molecular allergen-based component-resolved diagnostic IgE antibody tests have emerged in the form of singleplex assays and multiplex arrays. They use both native and recombinant allergen molecules, sometimes in combination with each other, to supplement allergen extract-based IgE antibody analyses. The total number of available allergenic molecules has reached a diagnostically useful level; however, more molecules are needed to cover all the clinically important allergen specificities. Thus, for the foreseeable future, molecular allergen specific IgE analyses will remain a supplement for initial allergen extract-based IgE antibody analyses in the diagnostic workup of the allergic patient. As a spin off, it will enable manufacturers to improve the quality of extracts for in vitro testing. The 2 most exciting diagnostic developments linked to component-resolved diagnostic tests are the possibility to increase diagnostic sensitivity by the inclusion of allergens that are underrepresented in the current extracts and in vitro assays and to increase the diagnostic specificity by taking the information on allergen cross-reactivity into account. Particularly the latter application is still under development. This requires additional studies on the clinical relevance of serological cross-reactivity. PMID- 26553614 TI - Clinical History-Driven Diagnosis of Allergic Diseases: Utilizing in vitro IgE Testing. AB - This case illustrates the importance of a thorough clinical history in providing an interpretation of previously collected IgE antibody serology as part of a workup for allergic disease. Although a yellow-jacket sting was the allergenic insult that led the patient to the emergency department, nonindicated IgE antibody serology tests were ordered that subsequently required interpretation. This report systematically evaluates the relative significance of previously measured IgE antibody serology responses to 4 major allergen groups (inhalants [aeroallergens], foods, venoms, and drugs) within the context of the patient's history. An algorithm that takes into account the pretest likelihood of disease and diagnostic sensitivity and specificity of the available IgE antibody tests is proposed for decisions about further IgE testing. This case study concludes that selection of testing methods, extract and molecular allergen specificities, and the final interpretation of the results from tests of sensitization such as serological (in vitro) IgE antibody assays requires knowledge of test parameters and clinical judgments based largely on a carefully collected clinical history and physical examination. PMID- 26553615 TI - Performance and Pain Tolerability of Current Diagnostic Allergy Skin Prick Test Devices. AB - BACKGROUND: Allergen skin prick testing remains an essential tool for diagnosing atopic disease and guiding treatment. Sensitivity needs to be defined for newly introduced devices. OBJECTIVE: Our aim was to compare the performance of 10 current allergy skin prick test devices. METHODS: Single- and multiheaded skin test devices (n = 10) were applied by a single operator in a prospective randomized manner. Histamine (1 and 6 mg/mL) and control diluent were introduced at 6 randomized locations onto the upper and lower arms of healthy subjects. Wheal and flare reactions were measured independently by 2 masked technicians. RESULTS: Twenty-four subjects provided consent, and 768 skin tests were placed. Mean wheal diameter among devices differed from 3.0 mm (ComforTen; Hollister Stier, Spokane, Wash) to 6.8 mm (UniTest PC; Lincoln Diagnostics, Decatur, Ill) using 1 mg/mL histamine (P < .001) and 4.8 mm (GREER Pick; Greer, Lenoir, NC) to 8.4 mm (Duotip-Test II; Lincoln Diagnostics, Decatur, Ill; and Sharp-Test; Panatrex, Placentia, Calif) using 6 mg/mL histamine (P < .001). The false negative rates ranged from 0% to 45% with 1 mg/mL histamine. The analytical specificity was 100% for all devices tested. All devices were well tolerated, with average pain score of less than 4 on a 10-point visual analog scale. Pain scores were higher among women, but this did not reach statistical significance. The Multi-Test PC and the UniTest PC had the lowest pain scores compared with the other devices. CONCLUSIONS: All 10 skin prick test devices displayed good analytical sensitivity and specificity; however, 3 mm cannot arbitrarily be used as a positive threshold. The use of histamine at 1 mg/mL is unacceptable for certain devices but may be preferable for the most sensitive devices. On average, there was no pain score difference between multiheaded and single-head devices. PMID- 26553616 TI - Are All Skin Testing Devices Created Equal? PMID- 26553617 TI - No Risk of Asthma in Late-Preterm Infants: Confounding or Misclassification? PMID- 26553618 TI - Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease: Consideration of a New Oral Challenge Protocol. PMID- 26553619 TI - Reliever Inhaler Overuse, Asthma Symptoms, and Depression. PMID- 26553620 TI - Preparing for the Next Big Thing in Asthma Management. PMID- 26553621 TI - Statin Allergy: An Evidence-Based Approach. PMID- 26553622 TI - Efficient Utilization of IgG for Antibody Replacement Therapy. PMID- 26553623 TI - Chronic Idiopathic Urticaria. PMID- 26553624 TI - Cephalosporin Side Chain Cross-reactivity. PMID- 26553625 TI - Bladder cancer: In the driving seat - AGL loss drives tumour growth. PMID- 26553626 TI - Dysregulated stress-related signalling pathways associated with lethality of prostate cancer. PMID- 26553627 TI - Prostate cancer: Online support reduces distress in men with prostate cancer. PMID- 26553628 TI - Prostate cancer: Effectiveness of abiraterone is unaffected by prior ADT. PMID- 26553630 TI - Ranking nodes in growing networks: When PageRank fails. AB - PageRank is arguably the most popular ranking algorithm which is being applied in real systems ranging from information to biological and infrastructure networks. Despite its outstanding popularity and broad use in different areas of science, the relation between the algorithm's efficacy and properties of the network on which it acts has not yet been fully understood. We study here PageRank's performance on a network model supported by real data, and show that realistic temporal effects make PageRank fail in individuating the most valuable nodes for a broad range of model parameters. Results on real data are in qualitative agreement with our model-based findings. This failure of PageRank reveals that the static approach to information filtering is inappropriate for a broad class of growing systems, and suggest that time-dependent algorithms that are based on the temporal linking patterns of these systems are needed to better rank the nodes. PMID- 26553629 TI - The selective expression of carbonic anhydrase genes of Aspergillus nidulans in response to changes in mineral nutrition and CO2 concentration. AB - Carbonic anhydrase (CA) plays an important role in the formation and evolution of life. However, to our knowledge, there has been no report on CA isoenzyme function differentiation in fungi. Two different CA gene sequences in Aspergillus nidulans with clear genetic background provide us a favorable basis for studying function differentiation of CA isoenzymes. Heterologously expressed CA1 was used to test its weathering ability on silicate minerals and real-time quantitative PCR was used to detect expression of the CA1 and CA2 genes at different CO2 concentrations and in the presence of different potassium sources. The northern blot method was applied to confirm the result of CA1 gene expression. Heterologously expressed CA1 significantly promoted dissolution of biotite and wollastonite, and CA1 gene expression increased significantly in response to soluble K-deficiency. The northern blot test further showed that CA1 participated in K-feldspar weathering. In addition, the results showed that CA2 was primary involved in adapting to CO2 concentration change. Taken together, A. nidulans can choose different CA to meet their survival needs, which imply that some environmental microbes have evolved different CAs to adapt to changes in CO2 concentration and acquire mineral nutrition so that they can better adapt to environmental changes. Inversely, their adaption may impact mineral weathering and/or CO2 concentration, and even global change. PMID- 26553632 TI - Rearing Tenebrio molitor L. (Coleptera: Tenebrionidae) in the "Lunar Palace 1" during a 105-day multi-crew closed integrative BLSS experiment. AB - Yellow mealworm (Tenebrio molitor L.) is one of the animal candidates for space bioregenerative life support systems. In this study, T. molitor was involved in a 105-day multi-crew closed integrative BLSS experiment for a tentative rearing study. The results showed that the overall bioconversion rate (ratio of T. molitor gained to the total feed consumed) of T. molitor reared in the closed system was 8.13%, while 78.43% of the feed was excreted as frass. T. molitor reared in the closed system had a good nutritional composition. The eight essential amino acids (EAAs) in T. molitor larvae accounted for 41.30% of its total amino acids, and most EAA contents were higher than the suggested amino acid pattern recommended by the FAO/WHO. T. molitor sample obtained in this work was high in polyunsaturated fatty acids, and low in saturated fatty acids, indicating that the composition of fatty acids was beneficial to human health. In the open environment outside the experimental system, we simultaneously reared three parallel groups of larval T. molitor using the same feeding regime and temperature condition. Compared with T. molitor reared in the open environment, larvae reared in the closed system grew slower. With the course of time t, the growth rate of T. molitor in the open environment was 0.839e(0.017t) times that of larvae in the closed system. This paper can provide data for future design and improvement of BLSS containing a T. molitor rearing unit. PMID- 26553631 TI - Combined exposure to protons and (56)Fe leads to overexpression of Il13 and reactivation of repetitive elements in the mouse lung. AB - Interest in deep space exploration underlines the needs to investigate the effects of exposure to combined sources of space radiation. The lung is a target organ for radiation, and exposure to protons and heavy ions as radiation sources may lead to the development of degenerative disease and cancer. In this study, we evaluated the pro-fibrotic and epigenetic effects of exposure to protons (150 MeV/nucleon, 0.1 Gy) and heavy iron ions ((56)Fe, 600 MeV/nucleon, 0.5 Gy) alone or in combination (protons on Day 1 and (56)Fe on Day 2) in C57BL/6 male mice 4 weeks after irradiation. Exposure to (56)Fe, proton or in combination, did not result in histopathological changes in the murine lung. At the same time, combined exposure to protons and (56)Fe resulted in pronounced molecular alterations in comparison with either source of radiation alone. Specifically, we observed a substantial increase in the expression of cytokine Il13, loss of expression of DNA methyltransferase Dnmt1, and reactivation of LINE-1, SINE B1 retrotransposons, and major and minor satellites. Given the deleterious potential of the observed effects that may lead to development of chronic lung injury, pulmonary fibrosis, and cancer, future studies devoted to the investigation of the long-term effects of combined exposures to proton and heavy ions are clearly needed. PMID- 26553633 TI - Prospects for using a full-scale installation for wet combustion of organic wastes in closed life support systems. AB - The issue of recycling organic wastes in closed life support systems (CLSS) includes both fundamental aspects of environmental safety of the recycled products and their effective involvement in material cycles and technical aspects related to the structure of the system and the crew's demands. This study estimates the effectiveness of wet combustion of different amounts of organic wastes in hydrogen peroxide under application of an alternating current electric field. The study also addresses the possibility of controlling the process automatically. The results show that processing of greater amounts of wastes reduces specific power consumption and shortens the duration of the process, without significantly affecting the level of oxidation of the products. An automatic control system for a semi-commercial installation has been constructed and tested experimentally. The solution of mineralized human wastes prepared in the automatically controlled process in this installation was successfully used to grow radish plants, with the main production parameters being similar to those of the control. PMID- 26553634 TI - Pancreas of C57 black mice after long-term space flight (Bion-M1 Space Mission). AB - In this study, we analysed the pancreases of C57BL/6N mice in order to estimate the effects of long-term space flights. Mice were flown aboard the Bion-M1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control group was used to account for housing effects. Each of the groups included mice designated for recovery studies. Mice pancreases were dissected for histological and immunohistochemical examinations. Using a morphometry and statistical analysis, a strong correlation between the mean islet size and the mean body weight was revealed in all groups. Therefore, we propose that hypokinesia and an increase in nutrition play an important role in alterations of the endocrine pancreas, both in space flight and terrestrial conditions. PMID- 26553635 TI - 3DHZETRN: Neutron leakage in finite objects. AB - The 3DHZETRN formalism was recently developed as an extension to HZETRN with an emphasis on 3D corrections for neutrons and light ions. Comparisons to Monte Carlo (MC) simulations were used to verify the 3DHZETRN methodology in slab and spherical geometry, and it was shown that 3DHZETRN agrees with MC codes to the degree that various MC codes agree among themselves. One limitation of such comparisons is that all of the codes (3DHZETRN and three MC codes) utilize different nuclear models/databases; additionally, using a common nuclear model is impractical due to the complexity of the software. It is therefore difficult to ascertain if observed discrepancies are caused by transport code approximations or nuclear model differences. In particular, an important simplification in the 3DHZETRN formalism assumes that neutron production cross sections can be represented as the sum of forward and isotropic components, where the forward component is subsequently solved within the straight-ahead approximation. In the present report, previous transport model results in specific geometries are combined with additional results in related geometries to study neutron leakage using the Webber 1956 solar particle event as a source boundary condition. A ratio is defined to quantify the fractional neutron leakage at a point in a finite object relative to a semi-infinite slab geometry. Using the leakage ratio removes some of the dependence on the magnitude of the neutron production and clarifies the effects of angular scattering and absorption with regard to differences between the models. Discussion is given regarding observed differences between the MC codes and conclusions drawn about the need for further code development. Although the current version of 3DHZETRN is reasonably accurate compared to MC simulations, this study shows that improved leakage estimates can be obtained by replacing the isotropic/straight-ahead approximation with more detailed descriptions. PMID- 26553636 TI - Natural microbial populations in a water-based biowaste management system for space life support. AB - The reutilization of wastewater is a key issue with regard to long-term space missions and planetary habitation. This study reports the design, test runs and microbiological analyses of a fixed bed biofiltration system which applies pumice grain (16-25 mm grain size, 90 m(2)/m(3) active surface) as matrix and calcium carbonate as buffer. For activation, the pumice was inoculated with garden soil known to contain a diverse community of microorganisms, thus enabling the filtration system to potentially degrade all kinds of organic matter. Current experiments over 194 days with diluted synthetic urine (7% and 20%) showed that the 7% filter units produced nitrate slowly but steadily (max. 2191 mg NO3 N/day). In the 20% units nitrate production was slower and less stable (max. 1411 mg NO3-N/day). 84% and 76% of the contained nitrogen was converted into nitrate. The low conversion rate is assumed to be due to the high flow rate, which keeps the biofilm on the pumice thin. At the same time the thin biofilm seems to prevent the activity of denitrifiers implicating the existence of a trade off between rate and the amount of nitrogen loss. Microbiological analyses identified a comparatively low number of species (26 in the filter material, 12 in the filtrate) indicating that urine serves as a strongly selective medium and filter units for the degradation of mixed feedstock have to be pre-conditioned on the intended substrates from the beginning. PMID- 26553638 TI - Water extraction on Mars for an expanding human colony. AB - In-situ water extraction is necessary for an extended human presence on Mars. This study looks at the water requirements of an expanding human colony on Mars and the general systems needed to supply that water from the martian atmosphere and regolith. The proposed combination of systems in order to supply the necessary water includes a system similar to Honeybee Robotics' Mobile In-Situ Water Extractor (MISWE) that uses convection, a system similar to MISWE but that directs microwave energy down a borehole, a greenhouse or hothouse type system, and a system similar to the Mars Atmospheric Resource Recovery System (MARRS). It is demonstrated that a large water extraction system that can take advantage of large deposits of water ice at site specific locations is necessary to keep up with the demands of a growing colony. PMID- 26553637 TI - Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss. AB - Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts. PMID- 26553639 TI - (16)Oxygen irradiation enhances cued fear memory in B6D2F1 mice. AB - The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of (16)O ion irradiation on cognitive performance of C57BL/6J * DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus independent cued fear memory of B6D2F1 mice were tested. (16)O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with (16)O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following (16)O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of (16)O ion exposure. PMID- 26553640 TI - Influence of extreme ambient temperatures and anaerobic conditions on Peltigera aphthosa (L.) Willd. viability. AB - Lichen are symbiotic systems constituted by heterotrophic fungi (mycobionts) and photosynthetic microorganism (photobionts). These organisms can survive under extreme stress conditions. The aim of this work was to study the influence of low (-70 degrees C) or high (+70 degrees C) temperatures, temperature fluctuations from +70 degrees C to -70 degrees C, and anaerobic conditions on P. aphthosa (L.) Willd. viability. None of the studied stress factors affected significantly photosynthetic and respiratory activity of the thalli. No changes in morphology or ultrastructure of the cells were revealed for both photobiont and mycobiont components after extreme temperature treatment of P. aphthosa thalli. The data show the extreme tolerance of P. aphthosa to some stress factors inherent to the space flight conditions. PMID- 26553641 TI - Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests. AB - One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor kappaB (NF-kappaB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 * g and 1 * g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of HEK cells to the beta-rays emitted by the radiation source dose-dependently decreased cell growth and increased NF-kappaB activation. The signal of the fluorescent proteins after formaldehyde fixation was stable for at least six months after fixation, allowing storage of the MPUs after fixation for several months before the transport back to Earth and evaluation of the fluorescence intensity. In conclusion, these tests show the feasibility of CellRad on the ISS with the currently available transport mechanisms. PMID- 26553642 TI - Neutron yields and effective doses produced by Galactic Cosmic Ray interactions in shielded environments in space. AB - In order to define the ranges of relevant neutron energies for the purposes of measurement and dosimetry in space, we have performed a series of Monte Carlo transport model calculations that predict the neutron field created by Galactic Cosmic Ray interactions inside a variety of simple shielding configurations. These predictions indicate that a significant fraction of the neutron fluence and neutron effective dose lies in the region above 20 MeV up to several hundred MeV. These results are consistent over thicknesses of shielding that range from very thin (2.7 g/cm(2)) to thick (54 g/cm(2)), and over both shielding materials considered (aluminum and water). In addition to these results, we have also investigated whether simplified Galactic Cosmic Ray source terms can yield predictions that are equivalent to simulations run with a full GCR source term. We found that a source using a GCR proton and helium spectrum together with a scaled oxygen spectrum yielded nearly identical results to a full GCR spectrum, and that the scaling factor used for the oxygen spectrum was independent of shielding material and thickness. Good results were also obtained using a GCR proton spectrum together with a scaled helium spectrum, with the helium scaling factor also independent of shielding material and thickness. Using a proton spectrum alone was unable to reproduce the full GCR results. PMID- 26553643 TI - Mars water discoveries--implications for finding ancient and current life. PMID- 26553644 TI - Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection. AB - BACKGROUND: The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa. METHODS: We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models. RESULTS: The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P?0.03). CONCLUSIONS: In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings. PMID- 26553645 TI - Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning. AB - Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson's disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin(-/-)) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin(-/-) mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin(-/-) brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory. PMID- 26553646 TI - Initial characterization of the large genome of the salamander Ambystoma mexicanum using shotgun and laser capture chromosome sequencing. AB - Vertebrates exhibit substantial diversity in genome size, and some of the largest genomes exist in species that uniquely inform diverse areas of basic and biomedical research. For example, the salamander Ambystoma mexicanum (the Mexican axolotl) is a model organism for studies of regeneration, development and genome evolution, yet its genome is ~10* larger than the human genome. As part of a hierarchical approach toward improving genome resources for the species, we generated 600 Gb of shotgun sequence data and developed methods for sequencing individual laser-captured chromosomes. Based on these data, we estimate that the A. mexicanum genome is ~32 Gb. Notably, as much as 19 Gb of the A. mexicanum genome can potentially be considered single copy, which presumably reflects the evolutionary diversification of mobile elements that accumulated during an ancient episode of genome expansion. Chromosome-targeted sequencing permitted the development of assemblies within the constraints of modern computational platforms, allowed us to place 2062 genes on the two smallest A. mexicanum chromosomes and resolves key events in the history of vertebrate genome evolution. Our analyses show that the capture and sequencing of individual chromosomes is likely to provide valuable information for the systematic sequencing, assembly and scaffolding of large genomes. PMID- 26553647 TI - A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds. AB - Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining "classic" gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID- 26553648 TI - Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells. AB - Chemo-resistance is the main factor for poor prognosis in human ovarian epithelial cancer. Active constituents derived from Chinese medicine with anti cancer potential might circumvent this obstacle. In our present study, evodiamine (EVO) derived from Evodia rutaecarpa (Juss.) Benth suppressed the proliferation of human epithelial ovarian cancer, A2780 and the related paclitaxel-resistant cell lines and did not cause cytotoxicity, as confirmed by the significant decline of clone formation and the representative alterations of CFDA-SE fluorescence. Meanwhile, EVO induced cell cycle arrest in a dose- and time dependent manner. This disturbance might be mediated by the cooperation of Cyclin B1 and Cdc2, including the up-regulation of Cyclin B1, p27, and p21, and activation failure of Cdc2 and pRb. MAPK signaling pathway regulation also assisted in this process. Furthermore, chemo-sensitivity potential was enhanced as indicated in A2780/PTX(R) cells by the down-regulation of MDR-1 expression, accompanied by MDR-1 function suppression. Taken together, we confirmed initially that EVO exerted an anti-proliferative effect on human epithelial ovarian cancer cells, A2780/WT and A2780/PTX(R), induced G2/M phase cell cycle arrest, and improved chemo-resistance. Overall, we found that EVO significantly suppressed malignant proliferation in human epithelial ovarian cancer, thus proving to be a potential anti-cancer agent in the future. PMID- 26553649 TI - Regulation of Primary Metabolism in Response to Low Oxygen Availability as Revealed by Carbon and Nitrogen Isotope Redistribution. AB - Based on enzyme activity assays and metabolic responses to waterlogging of the legume Lotus japonicus, it was previously suggested that, during hypoxia, the tricarboxylic acid cycle switches to a noncyclic operation mode. Hypotheses were postulated to explain the alternative metabolic pathways involved, but as yet, a direct analysis of the relative redistribution of label through the corresponding pathways was not made. Here, we describe the use of stable isotope-labeling experiments for studying metabolism under hypoxia using wild-type roots of the crop legume soybean (Glycine max). [(13)C]Pyruvate labeling was performed to compare metabolism through the tricarboxylic acid cycle, fermentation, alanine metabolism, and the gamma-aminobutyric acid shunt, while [(13)C]glutamate and [(15)N]ammonium labeling were performed to address the metabolism via glutamate to succinate. Following these labelings, the time course for the redistribution of the (13)C/(15)N label throughout the metabolic network was evaluated with gas chromatography-time of flight-mass spectrometry. Our combined labeling data suggest the inhibition of the tricarboxylic acid cycle enzyme succinate dehydrogenase, also known as complex II of the mitochondrial electron transport chain, providing support for the bifurcation of the cycle and the down-regulation of the rate of respiration measured during hypoxic stress. Moreover, up regulation of the gamma-aminobutyric acid shunt and alanine metabolism explained the accumulation of succinate and alanine during hypoxia. PMID- 26553651 TI - Prices of 18 new drug formulations are capped in India. PMID- 26553650 TI - Targets of the StBEL5 Transcription Factor Include the FT Ortholog StSP6A. AB - The BEL1-like family of transcription factors is ubiquitous in plants and plays important roles in regulating development. They function in tandem with KNOTTED1 types to bind to a double TTGAC motif in the upstream sequence of target genes. StBEL5 of potato (Solanum tuberosum) functions as a mobile RNA signal that is transcribed in leaves, moves down into stolons in response to short days, and induces tuber formation. Despite their importance, however, very little is known about the targets of BEL1-like transcription factors. To better understand this network, we made use of a phloem-mobile BEL5 induction model, an ethanol inducible system coupled with RNA sequencing analysis, and a screen for tandem TTGAC cis-elements in the upstream sequence to catalog StBEL5 target genes. Induction of StBEL5 activated several genes that are also induced by StSP6A (S. tuberosum SELF-PRUNING 6A), a FLOWERING LOCUS T coregulator that functions as a signal for tuberization. Both enhancement and suppression of StBEL5 expression were also closely linked to StSP6A transcriptional activity. Site mutagenesis in tandem TTGAC motifs located in the upstream sequence of StSP6A suppressed the short day-induced activity of its promoter in both young tubers and leaves. The expression profile of StBEL5 induced in stolons from plants grown under long-day conditions revealed almost 10,000 differentially expressed genes, including important tuber marker genes and genes involved in cell growth, transcription, floral development, and hormone metabolism. In a random screen of 200 differentially expressed targets of StBEL5, 92% contained tandem TTGAC motifs in the upstream sequence within 3 kb of the transcription start site. PMID- 26553652 TI - Upregulation of TGF-beta1 and basic FGF in elastofibroma: an immunohistochemical analysis. AB - Elastofibroma is a rare tumour that occurs in the subscapular space, and it typically presents in middle-aged and older individuals. The aetiology of elastofibroma remains unknown. Recent, sporadic reports have shown, immunohistologically, that fibroblasts in elastofibroma may produce abnormal elastic and collagen fibres through the action of transforming growth factor-beta (TGF-beta), a factor that promotes fibroblast proliferation. However, that finding lacked quantitative measurements and controls. Therefore, in this study, we performed quantitative, immunohistochemical analyses of TGF-beta1 and basic fibroblast growth factor (bFGF) in three elastofibromas, and we compared them to ten dermatofibromas and keloids, and five normal skin. In elastofibroma specimens, 16-59 % fibroblasts were positive for TGF-beta1 in the cytoplasm, compared to 96 % in dermatofibroma, 93 % in keloid and 2 % in normal dermis specimens. Also, in elastofibroma specimens, 26-67 % of fibroblasts were positive for bFGF in the cytoplasm, compared to 97 % in dermatofibroma, 97 % in keloid, and 22 % in normal dermis specimens. Intriguingly, the tumour size and growth rate were proportional to the percentage of cells positive for bFGF. Finally, greater levels of bFGF expressions in fibroblasts were associated with larger sized elastofibromas. These results suggested that elastofibroma development depended on high expression of TGF-beta1 and bFGF. PMID- 26553654 TI - Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice. AB - Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa. PMID- 26553655 TI - RANKL regulates differentiation of microfold cells in mouse nasopharynx associated lymphoid tissue (NALT). AB - Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation. PMID- 26553653 TI - VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance. AB - Despite being well-known for regulating angiogenesis in both normal and tumorigenic environments, vascular endothelial growth factor A (VEGFA) has been recently implicated in male fertility, namely in the maintenance of spermatogonial stem cells (SSC). The VEGFA gene can be spliced into multiple distinct isoforms that are either angiogenic or antiangiogenic in nature. Although studies have demonstrated the alternative splicing of VEGFA, including the divergent roles of the two isoform family types, many investigations do not differentiate between them. Data concerning VEGFA in the mammalian testis are limited, but the various angiogenic isoforms appear to promote seminiferous cord formation and to form a gradient across which cells may migrate. Treatment with either antiangiogenic isoforms of VEGFA or with inhibitors to angiogenic signaling impair these processes. Serendipitously, expression of KDR, the primary receptor for both types of VEGFA isoforms, was observed on male germ cells. These findings led to further investigation of the way that VEGFA elicits avascular functions within testes. Following treatment of donor perinatal male mice with either antiangiogenic VEGFA165b or angiogenic VEGFA164 isoforms, seminiferous tubules were less colonized following transplantation with cells from VEGFA165b treated donors. Thus, VEGFA165b and possibly other antiangiogenic isoforms of VEGFA reduce SSC number either by promoting premature differentiation, inducing cell death, or by preventing SSC formation. Thus, angiogenic isoforms of VEGFA are hypothesized to promote SSC self-renewal, and the divergent isoforms are thought to balance one another to maintain SSC homeostasis in vivo. PMID- 26553656 TI - Hoxc13 is a crucial regulator of murine hair cycle. AB - Hair follicles undergo cyclical growth and regression during postnatal life. Hair regression is an apoptosis-driven process strictly controlled by micro- and macro environmental signals. However, how these signals are controlled remains largely unknown. Hoxc13, a member of the Hox gene family, is reported to play an important role in hair follicle differentiation. In the present study, we observed that Hoxc13 was highly expressed in the outer root sheath, matrix, medulla and inner root sheath of hair follicles in a hair cycle-dependent manner. We therefore investigated the role of Hoxc13 in hair follicle cycling. Injection of ShRNA (ShHoxc13) to suppress Hoxc13 in early anagen promoted premature catagen entry, shown by significantly decreased hair length and hair bulb size, increased percentage of catagen hair follicles, hair cycle score and TUNEL+ cells and inhibited proliferation. In contrast, local injection of recombinant Hoxc13 polypeptide (rhHoxc13) during the late anagen phase prolonged the anagen phase. Additionally, rhHoxc13 injections during the telogen phase significantly promoted hair growth and induced the anagen progression. At the molecular level, the expression of phosphorylated smad2 (p-smad2), a key factor of active TGF-beta1 signaling, was up-regulated in the ShHoxc13-treated hair follicles and down regulated in rhHoxc13-treated hair follicles, suggesting that Hoxc13 might block anagen-catagen transition by inhibiting the TGF-beta1 signaling. Taken together, our data strongly suggest that Hoxc13 is a novel and crucial regulator of the hair cycle. This might also provide an understanding of the mechanism of the 'hair cycle clock' and the development of alopecia treatments. PMID- 26553657 TI - Involvement of phosphoinositide 3-kinase class IA (PI3K 110alpha) and NADPH oxidase 1 (NOX1) in regulation of vascular differentiation induced by vascular endothelial growth factor (VEGF) in mouse embryonic stem cells. AB - The impact of reactive oxygen species and phosphoinositide 3-kinase (PI3K) in differentiating embryonic stem (ES) cells is largely unknown. Here, we show that the silencing of the PI3K catalytic subunit p110alpha and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) by short hairpin RNA or pharmacological inhibition of NOX and ras-related C3 botulinum toxin substrate 1 (Rac1) abolishes superoxide production by vascular endothelial growth factor (VEGF) in mouse ES cells and in ES-cell-derived fetal liver kinase-1(+) (Flk 1(+)) vascular progenitor cells, whereas the mitochondrial complex I inhibitor rotenone does not have an effect. Silencing p110alpha or inhibiting Rac1 arrests vasculogenesis at initial stages in embryoid bodies, even under VEGF treatment, as indicated by platelet endothelial cell adhesion molecule-1 (PECAM-1)-positive areas and branching points. In the absence of p110alpha, tube-like structure formation on matrigel and cell migration of Flk-1(+) cells in scratch migration assays are totally impaired. Silencing NOX1 causes a reduction in PECAM-1 positive areas, branching points, cell migration and tube length upon VEGF treatment, despite the expression of vascular differentiation markers. Interestingly, silencing p110alpha but not NOX1 inhibits the activation of Rac1, Ras homologue gene family member A (RhoA) and Akt leading to the abrogation of VEGF-induced lamellipodia structure formation. Thus, our data demonstrate that the PI3K p110alpha-Akt/Rac1 and NOX1 signalling pathways play a pivotal role in VEGF-induced vascular differentiation and cell migration. Rac1, RhoA and Akt phosphorylation occur downstream of PI3K and upstream of NOX1 underscoring a role of PI3K p110alpha in the regulation of cell polarity and migration. PMID- 26553658 TI - Which Frail Older People Are Dehydrated? The UK DRIE Study. AB - BACKGROUND: Water-loss dehydration in older people is associated with increased mortality and disability. We aimed to assess the prevalence of dehydration in older people living in UK long-term care and associated cognitive, functional, and health characteristics. METHODS: The Dehydration Recognition In our Elders (DRIE) cohort study included people aged 65 or older living in long-term care without heart or renal failure. In a cross-sectional baseline analysis, we assessed serum osmolality, previously suggested dehydration risk factors, general health, markers of continence, cognitive and functional health, nutrition status, and medications. Univariate linear regression was used to assess relationships between participant characteristics and serum osmolality, then associated characteristics entered into stepwise backwards multivariate linear regression. RESULTS: DRIE included 188 residents (mean age 86 years, 66% women) of whom 20% were dehydrated (serum osmolality >300 mOsm/kg). Linear and logistic regression suggested that renal, cognitive, and diabetic status were consistently associated with serum osmolality and odds of dehydration, while potassium-sparing diuretics, sex, number of recent health contacts, and bladder incontinence were sometimes associated. Thirst was not associated with hydration status. CONCLUSIONS: DRIE found high prevalence of dehydration in older people living in UK long-term care, reinforcing the proposed association between cognitive and renal function and hydration. Dehydration is associated with increased mortality and disability in older people, but trials to assess effects of interventions to support healthy fluid intakes in older people living in residential care are needed to enable us to formally assess causal direction and any health benefits of increasing fluid intakes. PMID- 26553659 TI - The Mediating Roles of Primary and Secondary Control in the Relationship between Body Satisfaction and Subjective Well-Being Among Middle-Aged and Older Women. AB - Objectives: This study examined primary and secondary control as mediators in the relationship between body satisfaction and subjective well-being (SWB) and explored age differences in the mediation model. Method: Data from 362 women, aged 40-91 years, assessed (i) the relationships between body satisfaction, age, primary and secondary control strategies (body-specific social comparison, acceptance, and positive reappraisal), and three indices of SWB (positive affect, negative affect, and life satisfaction), (ii) the mediation effects of primary and secondary control on the relationship between body satisfaction and SWB, and (iii) whether mediational relationships were moderated by age. Results: Body satisfaction was unrelated to age but positively related to positive affect and life satisfaction and negatively related to negative affect. Body satisfaction was also related to primary and secondary control strategies. There were significant indirect (mediated) effects of body satisfaction on all outcome variables through acceptance and positive reappraisal. These mediators were significant at all age levels, but exerted their strongest influence among younger women. Discussion: This study provides new information about the mechanisms that influence the relationship between body satisfaction and SWB among a broad age range of women who are experiencing physical changes that are inconsistent with Western beauty standards. PMID- 26553660 TI - Outcomes of Laryngeal Reinnervation for Unilateral Vocal Fold Paralysis in Children: Associations With Age and Time Since Injury. AB - OBJECTIVE: Outcomes of laryngeal reinnervation with ansa-cervicalis for unilateral vocal fold paralysis (UVFP) may be influenced by age of the patient and time interval between laryngeal nerve injury and reinnervation, suggesting less favorable outcomes in older patients and greater than 2-year time interval after injury. This study examines these issues in the pediatric population. METHOD: Review of prospectively collected data set of 35 children and adolescents (1-21 years) that underwent ansa-recurrent laryngeal nerve (RLN) laryngeal reinnervation for UVFP. RESULTS: The time from RLN injury to reinnervation averaged 5.0 years (range, 0.8-15.2 years). No correlation was found between age at reinnervation (r = 0.15) and patient- or parent-reported global percentage voice outcome or perceptual ratings. There was slight negative correlation in duration between RLN injury and reinnervation and voice outcomes (r = -0.31). Postoperative voice self/surrogate global percentage rating average was 80.5% (range, 50%-100%), and perceptual rating GRBAS sum score average was 2.9 (range, 0-7). CONCLUSION: In pediatric ansa-RLN reinnervation for UVFP, no correlation between age at surgery and postoperative outcome was found. Denervation duration showed slight negative correlation, similar to what has been reported in adults, though voice improvement was seen in all patients. PMID- 26553661 TI - Early Cellular Response to Radiation in Human Vocal Fold Fibroblasts. AB - OBJECTIVES: Radiation therapy is a common treatment strategy for laryngeal carcinoma. However, radiation is not without adverse side effects, especially toward healthy vocal fold tissue, which can lead to long-term impairments in vocal function. The objective of this preliminary study was to investigate early responses of healthy human vocal fold fibroblasts (VFF) to radiation. METHODS: VFF were exposed to a single or fractionated dose radiation scheme. Nonradiated VFF served as controls. Morphology of radiated and control VFF was subjectively examined. Quantitative polymerase chain reaction was used to evaluate the effect of radiation on extracellular matrix and inflammatory-related genes. VFF viability was investigated using a LIVE/DEAD and clonogenic assay. RESULTS: Single or fractioned dose radiated VFF were morphologically indistinguishable from control VFF. No significant differences in gene expression were observed following either radiation scheme and as compared to controls. Clonogenic assay revealed reduced VFF viability following the fractionated but not single dose scheme. No changes in viability were detected using the LIVE/DEAD assay. CONCLUSIONS: We present one of the first investigations to evaluate early responses of healthy VFF to radiation. Findings will contribute to a growing body of literature seeking to elucidate the biological mechanisms underlying voice changes following radiation therapy for laryngeal carcinoma. PMID- 26553662 TI - Transumbilical thoracic sympathectomy: a single-centre experience of 148 cases with up to 4 years of follow-up?. AB - OBJECTIVES: Thoracic sympathectomy is considered as the most effective method to treat palmar hyperhidrosis (PH). Here, we report our experience of transumbilical thoracic sympathectomy with an ultrathin flexible endoscope for PH in a series of 148 patients with up to 4 years of follow-up. METHODS: A prospective database was used in this retrospective analysis of 148 patients (61 males, 87 females, with a mean age of 21.3 years) with PH who were operated on by the same surgeon in a single institution from April 2010 to March 2014. All procedures were performed under general anaesthesia involving intubation with a double-lumen endotracheal tube. Demographic, postoperative and long-term data of patients were recorded and statistical analyses were performed. All patients were followed up at least 6 months post procedure through clinic visits or telephone/e-mail interviews. RESULTS: The procedure was performed successfully in 148 of the 150 patients. Two patients had to be converted to conventional thoracoscopic procedure because of severe pleural adhesions. The mean operating time was 43 min (ranging from 39 to 107 min) and the mean postoperative length of stay was 1 day (range 1-4 days). All patients were interviewed 6-48 months after surgery and no diaphragmatic hernia or syndrome was observed. The rate of resolution of PH and axillary hyperhidrosis was 98 and 74.6%, respectively. Compensatory sweating was reported in 22.3% of patients. Almost all of the patients were satisfied with the surgical results and the cosmetic outcome of the incision. CONCLUSIONS: This preliminary human experience suggested that transumbilical thoracic sympathectomy was a safe and efficacious alternative to the conventional approach. This technique avoided the chronic pain and chest wall paraesthesia that are associated with the chest incision. In addition, this novel procedure afforded maximum cosmetic benefits. PMID- 26553663 TI - A Vaccine Meets Its Promise: Success in Controlling Epidemic Meningitis in Sub Saharan Africa. PMID- 26553664 TI - Documenting the Results of a Successful Partnership: A New Meningococcal Vaccine for Africa. PMID- 26553665 TI - From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project. AB - BACKGROUND: Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996-1997 (250,000 cases and 25,000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. METHODS: WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public-private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. RESULTS: The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the "cost of goods" to develop a group A - containing conjugate vaccine in the United States would be in the range of US$0.35-$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. CONCLUSIONS: In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis Vaccine Project (MVP) as a partnership between PATH and WHO, with the specific goal of developing an affordable MenA conjugate vaccine to eliminate MenA meningitis epidemics in Africa. EVA is an example of the use of WHO as an important convening instrument to facilitate new approaches to address major public health problems. PMID- 26553666 TI - The Evolution of the Meningitis Vaccine Project. AB - BACKGROUND: In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. METHODS: Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. RESULTS: A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. CONCLUSIONS: The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. PMID- 26553667 TI - Technical Development of a New Meningococcal Conjugate Vaccine. AB - BACKGROUND: Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide-protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success. METHODS: A monovalent MenA polysaccharide-tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization. RESULTS: A high efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine. CONCLUSIONS: Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine. PMID- 26553668 TI - Meningococcal Meningitis Surveillance in the African Meningitis Belt, 2004-2013. AB - BACKGROUND: An enhanced meningitis surveillance network was established across the meningitis belt of sub-Saharan Africa in 2003 to rapidly collect, disseminate, and use district weekly data on meningitis incidence. Following 10 years' experience with enhanced surveillance that included the introduction of a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in 2010, we analyzed the data on meningitis incidence and case fatality from countries reporting to the network. METHODS: After de-duplication and reconciliation, data were extracted from the surveillance bulletins and the central database held by the World Health Organization Inter-country Support Team in Burkina Faso for countries reporting consistently from 2004 through 2013 (Benin, Burkina Faso, Chad, Democratic Republic of Congo, Ghana, Cote d'Ivoire, Mali, Niger, Nigeria, Togo). RESULTS: The 10 study countries reported 341 562 suspected and confirmed cases over the 10-year study period, with a marked peak in 2009 due to a large epidemic of group A Neisseria meningitidis (NmA) meningitis. Case fatality was lowest (5.9%) during this year. A mean of 71 and 67 districts annually crossed the alert and epidemic thresholds, respectively. The incidence rate of NmA meningitis fell >10-fold, from 0.27 per 100,000 in 2004-2010 to 0.02 per 100,000 in 2011-2013 (P < .0001). CONCLUSIONS: In addition to supporting timely outbreak response, the enhanced meningitis surveillance system provides a global overview of the epidemiology of meningitis in the region, despite limitations in data quality and completeness. This study confirms a dramatic fall in NmA incidence after the introduction of PsA-TT. PMID- 26553669 TI - Community Perspectives Associated With the African PsA-TT (MenAfriVac) Vaccine Trials. AB - BACKGROUND: The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT. METHODS: Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death. RESULTS: The clinical trials were completed successfully through community acceptance and active community collaboration. The trials also strengthened the capacities in the participating communities, and actively worked to resolve community problems. CONCLUSIONS: The understanding and integration of sociocultural realities of communities were major assets in the conduct and acceptance of these trials. MVP succeeded in these sites and provided a sound example for future clinical studies in Africa. CLINICAL TRIALS REGISTRATION: ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN82484612 (PsA-TT 004); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007). PMID- 26553671 TI - Regulatory Pathways That Facilitated Timely Registration of a New Group A Meningococcal Conjugate Vaccine for Africa's Meningitis Belt Countries. AB - BACKGROUND: Through its normative and public health leadership roles, the World Health Organization (WHO) plays a key role in the availability of vaccine products in low-and middle-income countries. The recent introduction of a new group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in Africa exemplifies this process. WHO requires that any new vaccine to be introduced in countries for public health reasons and supplied through United Nations centralized mechanisms be licensed by the national regulatory agency (NRA) in the producing country, then prequalified and given a marketing authorization in the user countries. METHODS: PsA-TT was manufactured by the Serum Institute of India, Ltd (SIIL), which submitted a license application in April 2009 to the Drug Controller General of India (DCGI), the Indian NRA responsible for licensing vaccines. WHO encouraged the DCGI to establish a collaboration with Health Canada's Centre for Vaccine Evaluation for the review. Through this collaborative effort, registration was facilitated and in December 2009 an export license was granted to SIIL, which subsequently submitted an application for WHO prequalification. RESULTS: Given the importance of the vaccine, WHO "fast tracked" the prequalification review, and after a detailed review and site visit, WHO prequalification was granted to PsA-TT in June 2010. Country use of the new vaccine could not occur until the vaccine was a registered product in each country seeking its use. WHO facilitated country reviews by conducting regulatory training exercises (in French and English) for country NRA staff, which used the PsA-TT registration as a case study. CONCLUSIONS: PsA-TT was gradually registered in African countries as vaccine introduction proceeded. The regulatory pathway for this new group A meningococcal conjugate vaccine proved to be a useful training opportunity both in India and Africa, because the availability of the vaccine was a high African public health priority, as well as for WHO as a case study to facilitate registration of vaccines based on reliance on other regulatory bodies. PMID- 26553670 TI - Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine. AB - BACKGROUND: The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. METHODS: Because of the public-private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. RESULTS: Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. CONCLUSIONS: Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. CLINICAL TRIALS REGISTRATION: ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007). PMID- 26553672 TI - Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA TT) in African Meningitis Belt Countries, 2010-2014. AB - BACKGROUND: A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African "meningitis belt" and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. METHODS: With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. RESULTS: Burkina Faso was the first country to fully immunize its 1- to 29-year old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. CONCLUSIONS: The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary. PMID- 26553673 TI - Risk Assessment and Meningococcal A Conjugate Vaccine Introduction in Africa: The District Prioritization Tool. AB - BACKGROUND: A group A meningococcal (MenA) conjugate vaccine has progressively been introduced in the African meningitis belt since 2010. A country-wide risk assessment tool, the District Prioritization Tool (DPT), was developed to help national stakeholders combine existing data and local expertise to define priority geographical areas where mass vaccination campaigns should be conducted. METHODS: DPT uses an Excel-supported offline tool that was made available to the countries proposed for immunization campaigns. It used quantitative-qualitative methods, relying predominantly on evidence-based risk scores complemented by expert opinion. RESULTS: DPT was used by most of the countries that introduced the group A conjugate vaccine. Surveillance data enabled the computation of severity scores for meningitis at the district level (magnitude, intensity, and frequency). District data were scaled regionally to facilitate phasing decisions. DPT also assessed the country's potential to conduct efficient preventive immunization campaigns while paying close attention to the scope of the geographic extension of the campaigns. The tool generated meningitis district profiles that estimated the number of vaccine doses needed. In each assessment, local meningitis experts contributed their knowledge of local risk factors for meningitis epidemics to refine the final prioritization decisions. CONCLUSIONS: DPT proved to be a useful and flexible tool that codified information and streamlined discussion among stakeholders while facilitating vaccine distribution decisions after 2011. DPT methodology may be tailored to prioritize vaccine interventions for other diseases. PMID- 26553674 TI - Communication Challenges During the Development and Introduction of a New Meningococcal Vaccine in Africa. AB - BACKGROUND: A new group A meningococcal conjugate vaccine was developed to eliminate deadly meningitis epidemics in sub-Saharan Africa. METHODS: From the outset of the project, advocacy and communication strategies were developed and adjusted as the project evolved in Europe, Africa, India, and the United States. Communications efforts were evidence-based, and involved partnerships with the media and various stakeholders including African ministries of health, the World Health Organization, UNICEF, Gavi, the Centers for Disease Control and Prevention, and Medecins Sans Frontieres. RESULTS: The implementation of an integrated communication strategy ensured the active cooperation of stakeholders while providing an organized and defined format for the dissemination of project related developmental activities and the successful introduction of the vaccine. CONCLUSIONS: Early in the project, a communications strategy that engaged stakeholders and potential supporters was developed. The strategy was implemented and adapted as the project matured. Linked communication proved to be key to the successful wide-scale introduction of the PsA-TT (MenAfriVac) vaccine in Africa. PMID- 26553675 TI - Lessons Learned From Enhancing Vaccine Pharmacovigilance Activities During PsA-TT Introduction in African Countries, 2010-2013. AB - BACKGROUND: The rollout of the group A meningococcal vaccine, PsA-TT, in Africa's meningitis belt countries represented the first introduction of a vaccine specifically designed for this part of the world. During the first year alone, the number of people who received the vaccine through mass vaccination campaigns was several hundredfold higher than that of subjects who participated in the closely monitored clinical trials. Implementation of a system to identify rare but potentially serious vaccine reactions was therefore a high priority in the design and implementation of those campaigns. METHODS: National authorities and their technical partners set up effective vaccine pharmacovigilance systems, including conducting active surveillance projects. RESULTS: Implementation of national expert advisory groups to review serious adverse events following immunization in all countries and active monitoring of conditions of interest in 3 early-adopter countries did not identify particular concerns with the safety profile of PsA-TT, which had already provided tremendous public health benefits. CONCLUSIONS: Lessons learned from this experience will help to improve preparations for future vaccine introductions in resource-poor settings and capitalize on such efforts to advance vaccine safety systems in the future. PMID- 26553677 TI - Costs of Neisseria meningitidis Group A Disease and Economic Impact of Vaccination in Burkina Faso. AB - BACKGROUND: Five years since the successful introduction of MenAfriVac in a mass vaccination campaign targeting 1- to 29-year-olds in Burkina Faso, consideration must be given to the optimal strategies for sustaining population protection. This study aims to estimate the economic impact of a range of vaccination strategies in Burkina Faso. METHODS: We performed a cost-of-illness study, comparing different vaccination scenarios in terms of costs to both households and health systems over a 26-year time horizon. These scenarios are (1) reactive vaccination campaign (baseline comparator); (2) preventive vaccination campaign; (3) routine immunization at 9 months; and (4) a combination of routine and an initial catchup campaign of children under 5. Costs were estimated from a literature review, which included unpublished programmatic documents and peer reviewed publications. The future disease burden for each vaccination strategy was predicted using a dynamic transmission model of group A Neisseria meningitidis. RESULTS: From 2010 to 2014, the total costs associated with the preventive campaign targeting 1- to 29-year-olds with MenAfriVac were similar to the estimated costs of the reactive vaccination strategy (approximately 10 million US dollars [USD]). Between 2015 and 2035, routine immunization with or without a catch-up campaign of 1- to 4-year-olds is cost saving compared with the reactive strategy, both with and without discounting costs and cases. Most of the savings are accrued from lower costs of case management and household costs resulting from a lower burden of disease. After the initial investment in the preventive strategy, 1 USD invested in the routine strategy saves an additional 1.3 USD compared to the reactive strategy. CONCLUSIONS: Prevention strategies using MenAfriVac will be significantly cost saving in Burkina Faso, both for the health system and for households, compared with the reactive strategy. This will protect households from catastrophic expenditures and increase the development capacity of the population. PMID- 26553676 TI - Public Health Impact After the Introduction of PsA-TT: The First 4 Years. AB - BACKGROUND: During the first introduction of a group A meningococcal vaccine (PsA TT) in 2010-2011 and its rollout from 2011 to 2013, >150 million eligible people, representing 12 hyperendemic meningitis countries, have been vaccinated. METHODS: The new vaccine effectiveness evaluation framework was established by the World Health Organization and partners. Meningitis case-based surveillance was strengthened in PsA-TT first-introducer countries, and several evaluation studies were conducted to estimate the vaccination coverage and to measure the impact of vaccine introduction on meningococcal carriage and disease incidence. RESULTS: PsA-TT implementation achieved high vaccination coverage, and results from studies conducted showed significant decrease of disease incidence as well as significant reduction of oropharyngeal carriage of group A meningococci in vaccinated and unvaccinated individuals, demonstrating the vaccine's ability to generate herd protection and prevent group A epidemics. CONCLUSIONS: Lessons learned from this experience provide useful insights in how to guide and better prepare for future new vaccine introductions in resource-limited settings. PMID- 26553679 TI - The Safety of PsA-TT in Pregnancy: An Assessment Performed Within the Navrongo Health and Demographic Surveillance Site in Ghana. AB - BACKGROUND: Group A meningococcal disease occurs in large epidemics within the meningitis belt of Africa that includes northern Ghana. Major epidemics in the meningitis belt have infection rates ranging from 100 to 800 per 100 000 population. In 2012, a group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), was introduced into the region in large campaigns. METHODS: We report here on the safety of this vaccine when used in pregnant women in the Navrongo region of Ghana. RESULTS: Rates of events in 1730 immunized pregnant women and their infants were compared to the rates of the same events in pregnant women who did not receive the vaccine during the campaign and also to women who were pregnant in the prior year. CONCLUSIONS: We found no evidence of any safety concerns when this vaccine was administered during pregnancy. PMID- 26553678 TI - Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India. AB - BACKGROUND: In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. METHOD: From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. RESULTS: SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. CONCLUSIONS: The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries. PMID- 26553680 TI - Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali. AB - BACKGROUND: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. METHODS: The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1-29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. RESULTS: An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. CONCLUSIONS: No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries. PMID- 26553681 TI - Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons. AB - BACKGROUND: The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data. METHODS: In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4 7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events. Initial and ongoing training of sites' staff were undertaken during the studies, and a data and safety monitoring board reviewed all the data during and after the studies. RESULTS: The safety of PsA-TT was evaluated according to international standards despite obvious challenges in remote areas where these studies were conducted. These challenges included the need for uniformity of methods, timely reporting in the context of frequent communication problems, occurrence of seasonal diseases such as malaria and rotavirus diarrhea, and healthcare systems that required improvement. CONCLUSIONS: The trials of PsA-TT highlighted the value of a robust vaccine development plan and design so that lessons learned in initial studies were incorporated into the subsequent ones, initial training and periodic retraining, strict monitoring of all procedures, and continuous channel of communication with all stakeholders that enabled the application of international requirements to local settings, with high quality of data. PMID- 26553682 TI - A Phase 3, Double-Blind, Randomized, Active Controlled Study to Evaluate the Safety of MenAfriVac in Healthy Malians. AB - BACKGROUND: A safe, affordable, and highly immunogenic meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed to control epidemic group A meningitis in Africa. Documentation of the safety specifications of the PsA-TT vaccine was warranted, with sufficient exposure to detect potential rare vaccine-related adverse reactions. METHODS: This phase 3, double-blind, randomized, active controlled clinical study was designed to evaluate the safety--primarily vaccine related serious adverse events (SAEs)--up to 3 months after administration of a single dose of the PsA-TT vaccine to subjects aged 1-29 years in Mali. Safety outcomes were also compared to those following a single dose of a licensed meningococcal ACWY polysaccharide vaccine (PsACWY). RESULTS: No vaccine-related SAEs occurred during the 3 months of follow-up of 4004 subjects vaccinated with a single dose of PsA-TT. When compared to PsACWY (1996 subjects), tenderness at the injection site appeared to be more frequent in the PsA-TT group. However, rates of local induration, systemic reactions, adverse events (AEs), and SAEs were similar in both groups, and unsolicited AEs and SAEs were all unrelated to the study vaccines. CONCLUSIONS: The study confirmed on a large scale the excellent safety profile of a single dose of PsA-TT when administered to its entire target population of 1-29 years of age. CLINICAL TRIALS REGISTRATION: PACTR ATMR201003000191317. PMID- 26553683 TI - Antibody Persistence 1-5 Years Following Vaccination With MenAfriVac in African Children Vaccinated at 12-23 Months of Age. AB - BACKGROUND: Following mass vaccination campaigns in the African meningitis belt with group A meningococcal conjugate vaccine, MenAfriVac (PsA-TT), disease due to group A meningococci has nearly disappeared. Antibody persistence in healthy African toddlers was investigated. METHODS: African children vaccinated at 12-23 months of age with PsA-TT were followed for evaluation of antibody persistence up to 5 years after primary vaccination. Antibody persistence was evaluated by measuring group A serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Group A antibodies measured by SBA and ELISA were shown to decline in the year following vaccination and plateaued at levels significantly above baseline for up to 5 years following primary vaccination. CONCLUSIONS: A single dose of PsA-TT induces long-term sustained levels of group A meningococcal antibodies for up to 5 years after vaccination. CLINICAL TRIALS REGISTRATION: ISRTCN78147026. PMID- 26553685 TI - Influence of Age on Antibody Response and Persistence Following Immunization With MenAfriVac. AB - BACKGROUND: A meningococcal group A conjugate vaccine, PsA-TT (MenAfriVac), developed through the Meningitis Vaccine Project and manufactured by the Serum Institute of India, Ltd, was tested in multiple clinical trials conducted mainly in Africa. The impact of age at which subjects were vaccinated on immune response and persistence postimmunization with PsA-TT was the main focus of the current analysis. METHODS: Subjects who were vaccinated with a single dose of 10 ug of PsA-TT at 12-23 months or 22-33 months of age in study A conducted in Mali and The Gambia; at 2-10 years, 11-17 years, or 18-29 years of age in study B conducted in Mali, The Gambia, and Senegal; and at 14-18 weeks, 9-12 months, or 12-18 months of age in study C conducted in Ghana are included in the current analysis. Immunogenicity was measured by group A serum bactericidal antibody (SBA) titer with baby rabbit complement. RESULTS: Significant differences in SBA titers were found among the age groups in studies B and C both 28 days and 1 year postimmunization. A significant difference in SBA titers between age groups 12-23 months and 22-33 months was only observed 1 year postimmunization in study A. Antibody titers remained at similar levels from 1 to 2 years postimmunization for subjects vaccinated at 12-23 months in study A and at 9-12 months or 12-18 months of age in study C. CONCLUSIONS: Subjects immunized at different ages had different postimmunization immune responses as measured by SBA titers. Toddlers tended to have higher immune responses than infants. This pattern persisted at least 1 year postimmunization. CLINICAL TRIALS REGISTRATION: ISRCTN78147026 (study A), ISRCTN87739946 (study B), and ISRCTN82484612 (study C). PMID- 26553684 TI - Antibody Persistence at 1 and 4 Years Following a Single Dose of MenAfriVac or Quadrivalent Polysaccharide Vaccine in Healthy Subjects Aged 2-29 Years. AB - BACKGROUND: Mass vaccination campaigns of the population aged 1-29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated. METHODS: A total of 900 subjects aged 2-29 years were followed up for 4 years in Senegal, Mali, and The Gambia (study A). A total of 340 subjects aged 2-10 years were followed up for 1 year in India (study B). In study A, subjects were randomized in a 2:1 ratio, and in study B a 1:1 ratio to receive either PsA-TT or PsACWY. Immunogenicity was evaluated by measuring MenA serum bactericidal antibody (SBA) with rabbit complement and by a group A specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. RESULTS: In both studies, substantial SBA decay was observed at 6 months postvaccination in both vaccine groups, although more marked in the PsACWY group. At 1 year and 4 years (only for study A) postvaccination, SBA titers were relatively sustained in the PsA-TT group, whereas a slight increasing trend, more pronounced among the youngest, was observed in the participants aged <18 years in the PsACWY groups. The SBA titers were significantly higher in the PsA-TT group than in the PsACWY group at any time point, and the majority of subjects in the PsA-TT group had SBA titers >=128 and group A-specific IgG concentrations >=2 ug/mL at any point in time in both the African and Indian study populations. CONCLUSIONS: Four years after vaccination with a single dose of PsA-TT vaccine in Africa, most subjects are considered protected from MenA disease. CLINICAL TRIALS REGISTRATION: PsA-TT 003 (ISRCTN87739946); PsA-TT-003a (ISRCTN46335400). PMID- 26553686 TI - Meningococcal Seroepidemiology 1 Year After the PsA-TT Mass Immunization Campaign in Burkina Faso. AB - BACKGROUND: A group A meningococcal (MenA) conjugate vaccine, PsA-TT (MenAfriVac), was introduced in Burkina Faso via mass campaigns between September and December 2010, targeting the 1- to 29-year-old population. This study describes specific antibody titers in the general population 11 months later and compares them to preintroduction data obtained during 2008 using the same protocol. METHODS: During October-November 2011, we recruited a representative sample of the population of urban Bobo-Dioulasso aged 6 months to 29 years, who underwent standardized interviews and blood draws. We assessed anti-MenA immunoglobulin G (IgG) concentrations (n = 200) and, using rabbit complement, serum bactericidal antibody (SBA) titers against 2 group A strains: reference strain F8238 (SBAref) (n = 562) and strain 3125 (SBA3125) (n = 200). RESULTS: Among the 562 participants, 481 (86%) were aged >=23 months and had been eligible for the PsA-TT campaign. Among them, vaccine coverage was 86.3% (95% confidence interval [CI], 82.7%-89.9%). Prevalence of putatively protective antibodies among vaccine-eligible age groups was 97.3% (95% CI, 95.9%-98.7%) for SBAref titers >=128, 83.6% (95% CI, 77.6%-89.7%) for SBA3125 >=128, and 84.2% (95% CI, 78.7% 89.7%) for anti-MenA IgG >=2 ug/mL. Compared to the population aged 23 months to 29 years during 2008, geometric mean titers of SBAref were 7.59-fold higher during 2011, 51.88-fold for SBA3125, and 10.56-fold for IgG. CONCLUSIONS: This study shows high seroprevalence against group A meningococci in Burkina Faso following MenAfriVac introduction. Follow-up surveys will provide evidence on the persistence of population-level immunity and the optimal vaccination strategy for long-term control of MenA meningitis in the African meningitis belt. PMID- 26553687 TI - Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass Vaccination Campaign in Mali. AB - BACKGROUND: In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide-tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. METHODS: We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. RESULTS: Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3% 99.7%) maintained NmA-specific rSBA titers >=8, the accepted threshold for protection; 98.6% (95% CI, 97.8%-99.4%) had titers >=128, and 89.5% (95% CI, 87.4%-91.6%) had titers >=1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels >=2 ug/mL were found in 88.5% (95% CI, 86.3%-90.7%) of participants. CONCLUSIONS: Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population based seroprevalence studies complement clinical trials and provide this key evidence. PMID- 26553688 TI - Human Complement Bactericidal Responses to a Group A Meningococcal Conjugate Vaccine in Africans and Comparison to Responses Measured by 2 Other Group A Immunoassays. AB - BACKGROUND: PsA-TT (MenAfriVac) is a conjugated polysaccharide vaccine developed to eliminate group A meningococcal disease in Africa. Vaccination of African study participants with 1 dose of PsA-TT led to the production of anti-A polysaccharide antibodies and increased serum bactericidal activity measured using rabbit complement (rSBA). Bactericidal responses measured with human complement (hSBA) are presented here. METHODS: Sera collected before and at 28 days and 1 year after vaccination with either PsA-TT or quadrivalent polysaccharide vaccine (PsACWY) from a random, age-distributed 360-subject subset of the Meningitis Vaccine Project study of PsA-TT in Africans aged 2-29 years were tested for hSBA. Geometric mean titer, fold-rise, and threshold analyses were compared between vaccine groups and age groups. hSBA, rSBA, and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) results were compared and assay correlation and agreement determined. RESULTS: hSBA responses to PsA-TT were substantially higher than those to PsACWY at 28 days and 1 year following immunization, similar to previously reported rSBA and IgG results. The hSBA and IgG ELISA results identified differences between age groups that were not evident by rSBA. The rSBA data indicated sustained high titers 1 year after immunization, whereas hSBA GMTs at 1 year approached 4 in young children. CONCLUSIONS: The high level of protection following PsA-TT immunization campaigns is consistent with the strong hSBA immune responses observed here. Future implementation decisions will likely depend on immunologic data and their long term correlation with disease and carriage prevention. Expanded immunologic and epidemiologic surveillance may improve the interpretation of differences between these immunoassays. PMID- 26553689 TI - Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12-23 Months Following Meningococcal Vaccination. AB - BACKGROUND: A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12-23 months of age. METHODS: Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A-specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. RESULTS: The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 ug/mL and 6.27 ug/mL, whereas in the PsACWY group the mean GMCs were 2.01 ug/mL and 0.97 ug/mL, respectively (P < .0001). Group A-specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 ug/mL and 36.12 ug/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell-dependent response associated with conjugate vaccines. CONCLUSIONS: Vaccination of African children aged 12-24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell-independent immune response commonly associated with polysaccharide antigens. CLINICAL TRIALS REGISTRATION: SRCTN78147026. PMID- 26553690 TI - MenAfriVac as an Antitetanus Vaccine. AB - BACKGROUND: The group A meningococcal conjugate vaccine, PsA-TT, uses tetanus toxoid (TT) as a carrier protein (PsA-TT). TT as a carrier protein in other conjugate vaccines is known to be immunogenic and generates a robust anti-TT response. METHODS: Clinical studies in Africa assessed whether PsA-TT generated tetanus serologic responses when tested in African populations (toddlers to adults). Second, the high acceptance of PsA-TT mass immunization campaigns in the 1- to 29-year age group meant that a sizeable fraction of women of reproductive age received PsA-TT. Incidence data for neonatal tetanus were reviewed for countries with and without PsA-TT campaigns to check whether this had any impact on the incidence. RESULTS: PsA-TT generated robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT. Neonatal cases of tetanus fell by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. CONCLUSIONS: Although these data are not yet definitive, they are consistent with the hypothesis that improved community immunity to tetanus as a result of the PsA-TT campaigns may be having an impact on the incidence of neonatal tetanus in sub-Saharan Africa. CLINICAL TRIALS REGISTRATION: ISRCTN17662153 (PsA-TT 001); ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN46335400 (PsA-TT 003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT 005); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007). PMID- 26553691 TI - Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali. AB - BACKGROUND: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. METHODS: Using a household-based, age stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels >=0.1 IU/mL (indicating short-term protection) and >=1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. RESULTS: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination. CONCLUSIONS: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity. PMID- 26553692 TI - Immunogenicity of Yellow Fever Vaccine Coadministered With MenAfriVac in Healthy Infants in Ghana and Mali. AB - BACKGROUND: Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. METHODS: Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. RESULTS: In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. CONCLUSIONS: Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. CLINICAL TRIALS REGISTRATION: ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007). PMID- 26553693 TI - Modeling Long-term Vaccination Strategies With MenAfriVac in the African Meningitis Belt. AB - BACKGROUND: The introduction of MenAfriVac in campaigns targeting people aged 1 29 years across the African meningitis belt has successfully reduced meningitis incidence and carriage due to Neisseria meningitidis group A (MenA). It is important to consider how best to sustain population protection in the long term. METHODS: We created a mathematical model of MenA transmission and disease to investigate the potential impact of a range of immunization strategies. The model is age structured; includes classes of susceptible, carrier, ill, and immune people (who may be vaccinated or unvaccinated); and incorporates seasonal transmission and a stochastic forcing term that models between year variation in rates of transmission. Model parameters were primarily derived from African sources. The model can describe the typical annual incidence of meningitis in the prevaccine era, with irregular epidemics of varying size. Parameter and structural uncertainty were explored in sensitivity analyses. RESULTS: Following MenAfriVac introduction at high uptake, the model predicts excellent short-term disease control. With no subsequent immunization, strong resurgences in disease incidence were predicted after approximately 15 years (assuming 10 years' average vaccine protection). Routine immunization at 9 months of age resulted in lower average annual incidence than regular mass campaigns of 1- to 4-year-olds, provided coverage was above approximately 60%. The strategy with the lowest overall average annual incidence and longest time to resurgence was achieved using a combination strategy of introduction into the Expanded Programme on Immunization at 9 months, 5 years after the initial mass campaigns, with a catch up targeting unvaccinated 1- to 4-year-olds. CONCLUSIONS: These results can be used to inform policy recommendations for long-term vaccination strategies with MenAfriVac. PMID- 26553694 TI - Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs. AB - BACKGROUND: MicroRNAs are key players in cardiac stress responses, but the mRNAs, whose abundance and translational potential are primarily affected by changes in cardiac microRNAs, are not well defined. Stimulus-induced, large-scale alterations in the cardiac transcriptome, together with consideration of the law of mass action, further suggest that the mRNAs most substantively targeted by individual microRNAs will vary between unstressed and stressed conditions. To test the hypothesis that microRNA target profiles differ in health and disease, we traced the fate of empirically determined miR-133a and miR-378 targets in mouse hearts undergoing pressure overload hypertrophy. METHODS AND RESULTS: Ago2 immunoprecipitation with RNA sequencing (RNA-induced silencing complex sequencing) was used for unbiased definition of microRNA-dependent and microRNA independent alterations occurring among ~13 000 mRNAs in response to transverse aortic constriction (TAC). Of 37 direct targets of miR-133a defined in unstressed hearts (fold change >=25%, false discovery rate <0.02), only 4 (11%) continued to be targeted by miR-133a during TAC, whereas for miR-378 direct targets, 3 of 32 targets (9%) were maintained during TAC. Similarly, only 16% (for miR-133a) and 53% (for miR-378) of hundreds of indirectly affected mRNAs underwent comparable regulation, demonstrating that the effect of TAC on microRNA direct target selection resulted in widespread alterations of signaling function. Numerous microRNA-mediated regulatory events occurring exclusively during pressure overload revealed signaling networks that may be responsive to the endogenous decreases in miR-133a during TAC. CONCLUSIONS: Pressure overload-mediated changes in overall cardiac RNA content alter microRNA targeting profiles, reinforcing the need to define microRNA targets in tissue-, cell-, and status-specific contexts. PMID- 26553695 TI - Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease. AB - BACKGROUND: Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. METHODS AND RESULTS: A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5*10(-6) in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33*10(-5)). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. CONCLUSIONS: This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. PMID- 26553696 TI - Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy-Associated Mutation in Human Cardiac Troponin I (K206I). AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCM-associated mutation (K206I-TNNI3) and elucidate the mechanism of dysfunction at the level of myofilament proteins. METHODS AND RESULTS: The male index case was diagnosed with HCM after an out-of hospital cardiac arrest, which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca(2+) dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wild-type human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype and measured force generation. The Ca(2+) sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 umol/L (-)-epigallocatechin gallate (green tea) was restored back to wild-type levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of calcium-bound human cardiac troponin C. The ability of calcium bound human cardiac troponin C to neutralize the inhibition of K206I was greater than with wild-type TnI. CONCLUSIONS: Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM. PMID- 26553697 TI - Pulmonary artery denervation reduces pulmonary artery pressure and induces histological changes in an acute porcine model of pulmonary hypertension. AB - BACKGROUND: Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. METHODS AND RESULTS: Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. CONCLUSIONS: Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID- 26553698 TI - Efficacy of ex vivo autologous and in vivo platelet transfusion in the reversal of P2Y12 inhibition by clopidogrel, prasugrel, and ticagrelor: the APTITUDE study. AB - BACKGROUND: Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy. METHODS AND RESULTS: In the Antagonize P2Y12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or Delayed Timing After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included. PT was performed ex vivo by mixing platelet-rich plasma from blood sampling performed at baseline in increasing proportions with platelet-rich plasma sampled 4 hours after loading dose. The percentage restoration of residual platelet aggregation achieved with 80% proportion PT (residual platelet aggregation 80% PT mix/residual platelet aggregation baseline*100) significantly decreased with increasing potency of P2Y12 RI (83.9+/-11%, 73+/-14%, 66.3+/-15%, 40.9+/-19% for clopidogrel 600 mg, clopidogrel 900 mg, prasugrel, and ticagrelor, respectively; P for trend <0.0001). In the APTITUDE-Coronary Artery Bypass Graft (APTITUDE-CABG) study, vasodilator-stimulated phosphoprotein-platelet reactivity index, a specific marker of the P2Y12 RI drug-effect, was assessed before and after in vivo PT administered for excessive bleeding in patients undergoing cardiac surgery while on a maintenance dose of aspirin and clopidogrel (n=45), prasugrel (n=6), or ticagrelor (n=3). When compared with baseline, there was a significant relative increase of 23.1% in platelet activation after PT transfusion (42.2+/-23.6% versus 56.6+/-18.2%; P=0.0008). CONCLUSIONS: PT restores platelet reactivity in patients with acute coronary syndrome/percutaneous coronary intervention and in patients undergoing cardiac surgery on P2Y12 RI while bleeding with a less effect with increasing potency of P2Y12 inhibition. CLINICAL TRIAL REGISTRATION: URL: http://www.recherche-biomedicale.sante.gouv.fr/pro/comites/coordonnees.htm and http://www.cnil.fr/. Unique identifiers: No. 301111 and No. 1547216v0. PMID- 26553700 TI - First reported case of transcatheter mitral valve implantation in mitral annular calcification with a fully repositionable and self-expanding valve. PMID- 26553699 TI - Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. AB - BACKGROUND: The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes. METHODS AND RESULTS: Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure >=25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of -10 mm Hg and -7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths. CONCLUSIONS: PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.trc.com.cn. Unique identifier: chiCTR ONC-12002085. PMID- 26553701 TI - Restoring platelet function in patients on P2Y12 receptor inhibitor treatment: still some issues to be solved! PMID- 26553702 TI - Catheter-based therapies for patients with medication-refractory pulmonary arterial hypertension. PMID- 26553703 TI - [Blastic plasmacytoid dendritic cell neoplasm: two case reports]. AB - Blastic plasmacytoid dendritic cell neoplasm (LPDC) is a rare and aggressive leukemia entity with cutaneous and extracutaneous involvement, reaching most often lymph, blood and bone marrow. Two cases of LPDC diagnosed in Hospital Center of Le Mans are reported, a 78 year old woman (case 1) and a 82 year old man (case 2), and have been clinically, biologically and histologically documented. The clinical presentation, diagnostic difficulties are reminded, as well as the pathogenesis and therapeutic aspect. PMID- 26553704 TI - Pemphigus and depression comorbidity: a case control study. AB - BACKGROUND: While quality of life can be significantly affected in pemphigus patients, few studies have systematically investigated the co-morbidity of psychiatric disorders in these patients. OBJECTIVE: To assess the association between pemphigus and depression comorbidity, using the computerized medical database of Israel's largest health maintenance organization. METHODS: In a case control study, co-morbidities of adult pemphigus patients retrieved from the database of a large healthcare organization from 1998 to 2010 were compared with age- and gender-matched controls from the same database. The main outcome measure was the prevalence of co-morbid psychiatric disorders (anxiety, psychosis, schizophrenia and depression) in pemphigus patients and controls. The study included 255 pemphigus patients (157 women (62%) and 98 (38%) men) and 509 controls (313 women (62%) and 196 (38%) men) aged 20 years and older (a ratio of 3:2 in both groups). Mean age was 63.5 +/- 15.7 years in the pemphigus group and 63.2 +/- 15.7 years in the control group. RESULTS: Depression was the only psychiatric disorder significantly increased among pemphigus patients compared with controls. Alcohol abuse and smoking did not differ between groups. Depression was over-represented in a large population of pemphigus patients, indicating the disorder as a possible significant co-morbidity. After controlling for confounders including age, gender, and duration of corticosteroid therapy, the association with depression persisted (OR = 1.19, 95% CI: 1.12-1.27), p<0.001). CONCLUSION: The increased prevalence of depressive morbidity, especially in the presence of commonly prescribed corticosteroid treatment, emphasizes the need for psychiatric assessment and intervention in these patients. PMID- 26553705 TI - Non-invasive prenatal screening for trisomy 21: Consumers' perspectives. AB - Non-invasive prenatal screening (NIPS) has the potential to dramatically increase the prenatal detection rate of Down syndrome because of improvements in safety and accuracy over existing tests. There is concern that NIPS could lead to more negative attitudes towards Down syndrome and less support for individuals with Down syndrome. To assess the impact of NIPS on support for prenatal testing, decision-making about testing, and beliefs or attitudes about Down syndrome, we performed an Internet-based experiment using adults (N = 1,789) recruited through Amazon Mechanical Turk. Participants were randomly assigned to read a mock news article about NIPS, a mock news article about amniocentesis, or no article. The content in the two articles varied only in their descriptions of the test characteristics. Participants then answered questions about their support for testing, hypothetical testing decision, and beliefs and attitudes about Down syndrome. Reading the mock NIPS news article predicted increased hypothetical test uptake. In addition, the NIPS article group also agreed more strongly that pregnant women, in general, should utilize prenatal testing. We also found that the more strongly participants supported prenatal testing for pregnant women, the less favorable their attitudes towards individuals with Down syndrome; providing some evidence that NIPS may indirectly result in more negative perceptions of individuals with this diagnosis. PMID- 26553706 TI - Body proportions in children with Kabuki syndrome. AB - Facial characteristics, short stature, and skeletal anomalies have been described for the clinical diagnosis of Kabuki Syndrome (KS) in children. However, no studies have investigated body proportions in KS. Knowledge of body proportions in KS may contribute to better insight into the growth pattern and characterization of this genetic disorder. Therefore we compared body proportions of children with KS to normally proportioned controls to investigate if atypical body proportions are part of this genetic disorder. This study was designed and conducted within the setting of the Maastricht University Medical Centre (MUMC+), the official Dutch expert center for Kabuki syndrome. We conducted a cross sectional study in 32 children (11 children with KS and 21 controls). Body proportions were determined by means of photogrammetric anthropometry, measurements based on digital photography. Body proportions, quantified as body ratios, differ significantly in children with KS from normally proportioned children. Children with KS have larger heads and longer arms proportional to their trunks and have been found to have longer upper arms proportional to their tibia length and feet. Based on deviations in body proportions it was shown possible to discern children with KS from normally proportioned controls. PMID- 26553707 TI - Ultrapreconcentration and determination of organophosphorus pesticides in water by solid-phase extraction combined with dispersive liquid-liquid microextraction and high-performance liquid chromatography. AB - Solid-phase extraction coupled with dispersive liquid-liquid microextraction was developed as an ultra-preconcentration method for the determination of four organophosphorus pesticides (isocarbophos, parathion-methyl, triazophos and fenitrothion) in water samples. The analytes considered in this study were rapidly extracted and concentrated from large volumes of aqueous solutions (100 mL) by solid-phase extraction coupled with dispersive liquid-liquid microextraction and then analyzed using high performance liquid chromatography. Experimental variables including type and volume of elution solvent, volume and flow rate of sample solution, salt concentration, type and volume of extraction solvent and sample solution pH were investigated for the solid-phase extraction coupled with dispersive liquid-liquid microextraction with these analytes, and the best results were obtained using methanol as eluent and ethylene chloride as extraction solvent. Under the optimal conditions, an exhaustive extraction for four analytes (recoveries >86.9%) and high enrichment factors were attained. The limits of detection were between 0.021 and 0.15 MUg/L. The relative standard deviations for 0.5 MUg/L of the pesticides in water were in the range of 1.9-6.8% (n = 5). The proposed strategy offered the advantages of simple operation, high enrichment factor and sensitivity and was successfully applied to the determination of four organophosphorus pesticides in water samples. PMID- 26553708 TI - Cell-free plasma hemoglobin removal by dialyzers with various permeability profiles. AB - The release of hemoglobin from mechanically stressed erythrocytes into plasma is a general side effect of extracorporeal therapies, such as extracorporeal membrane oxygenation or hemodialysis. In many reported cases dialysis patients showed elevated cell-free plasma hemoglobin (CPH) levels which are associated with pathophysiological effects. In this in vitro study, the CPH clearance capacity of various filters with different permeability profiles was measured. Simulated dialysis treatments were conducted and clearance was calculated from variations in CPH concentrations over time by measuring plasma absorbance at 405 nm. Conventional high-flux filters exhibited no detectable clearance of CPH. High flux filters with extended permeability exhibited clearances between 5.8 +/- 1.2 and 12.7 +/- 1.7 ml/min when tested with plasma and between 5.8 +/- 1.2 and 11.3 +/- 1.6 ml/min when tested with whole blood. septeX high-cutoff filters had clearances between 13.8 +/- 1.8 and 15.5 +/- 1.7 ml/min when tested with plasma and of 22.6 +/- 2.9 ml/min when tested with whole blood. This study demonstrated that filters with extended permeability and the septeX filter enable CPH removal when used as in chronic and acute settings. PMID- 26553709 TI - Facile room-temperature synthesis of carboxylated graphene oxide-copper sulfide nanocomposite with high photodegradation and disinfection activities under solar light irradiation. AB - Carboxylic acid functionalized graphene oxide-copper (II) sulfide nanoparticle composite (GO-COOH-CuS) was prepared from carboxylated graphene oxide and copper precursor in dimethyl sulfoxide (DMSO) by a facile synthesis process at room temperature. The high-effective combination, the interaction between GO-COOH sheets and CuS nanoparticles, and the enhanced visible light absorption were confirmed by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS) and Photoluminescence (PL) spectra. The as-synthesized GO-COOH-CuS nanocomposite exhibited excellent photocatalytic degradation performance of phenol and rhodamine B, high antibacterial activity toward E. coli and B. subtilis, and good recovery and reusability. The influence of CuS content, the synergistic reaction between CuS and GO-COOH, and the charge-transfer mechanism were systematically investigated. The facile and low-energy synthesis process combined with the excellent degradation and antibacterial performance signify that the GO-COOH-CuS has a great potential for water treatment application. PMID- 26553711 TI - A novel method to quantify the emission and conversion of VOCs in the smoking of electronic cigarettes. AB - An analytical technique was developed for the quantitation of volatile organic compounds (VOC) in three different forms of electronic cigarette (EC): solution, vapor, and aerosol. Through the application of the mass change tracking (MCT) approach, the consumed amount of the solution was measured to track the conversion of targets between the different phases. The concentration of aerosol plus vapor (A&V) decreased exponentially (559 to 129 g m(-3)) with increasing puff velocity (0.05 to 1 L min(-1)). A strong correlation existed between sampling volume and consumed solution mass (R(2) = 0.9972 +/- 0.0021 (n = 4)). In the EC solution, acetic acid was considerably high (25.8 MUg mL(-1)), along with trace quantities of some VOCs (methyl ethyl ketone, toluene, propionic acid, and i-butyric acid: 0.24 +/- 0.15 MUg mL(-1) (n = 4)). In the aerosol samples, many VOCs (n-butyraldehyde, n-butyl acetate, benzene, xylene, styrene, n-valeric acid, and n-hexanoic acid) were newly produced (138 +/- 250 MUg m(-3)). In general, the solution-to-aerosol (S/A) conversion was significant: e.g., 1,540% for i-butyric acid. The emission rates of all targets computed based on their mass in aerosol/ consumed solution (ng mL(-1)) were from 30.1 (p-xylene) to 398 (methyl ethyl ketone), while those of carboxyls were much higher from 166 (acetic acid) to 5,850 (i-butyric acid). PMID- 26553710 TI - New genetic regulators question relevance of abundant yolk protein production in C. elegans. AB - Vitellogenesis or maternal yolk formation is considered critical to the reproduction of egg-laying animals. In invertebrates, however, most of its regulatory genes are still unknown. Via a combined mapping and whole-genome sequencing strategy, we performed a forward genetic screen to isolate novel regulators of yolk production in the nematode model system Caenorhabditis elegans. In addition to isolating new alleles of rab-35, rab-10 and M04F3.2, we identified five mutant alleles corresponding to three novel regulatory genes potently suppressing the expression of a GFP-based yolk reporter. We confirmed that mutations in vrp-1, ceh-60 and lrp-2 disrupt endogenous yolk protein synthesis at the transcriptional and translational level. In contrast to current beliefs, our discovered set of mutants with strongly reduced yolk proteins did not show serious reproduction defects. This raises questions as to whether yolk proteins per se are needed for ultimate reproductive success. PMID- 26553712 TI - Introduction to the Cardio-Oncology Miniseries. PMID- 26553713 TI - Myocardial Protection During Cardiotoxic Chemotherapy. PMID- 26553714 TI - ECG Response: November 10, 2015. PMID- 26553715 TI - Extensive Intramural Esophageal Hematoma After Transesophageal Echocardiography During Atrial Fibrillation Ablation. PMID- 26553716 TI - Neonatal Management of a Giant Right Atrial Appendage Aneurysm. PMID- 26553717 TI - Letter by Salzberg and Emmert Regarding Article, "Left Atrial Appendage Occlusion Debate Revisited". PMID- 26553718 TI - Response to Letter Regarding Article, "Left Atrial Appendage Occlusion Debate Revisited". PMID- 26553719 TI - Letter by Mahajan et al Regarding Article, "Systematic Review of Patients Presenting With Suspected Myocardial Infarction and Nonobstructive Coronary Arteries". PMID- 26553720 TI - Response to Letter Regarding Article, "Systematic Review of Patients Presenting With Suspected Myocardial Infarction and Nonobstructive Coronary Arteries". PMID- 26553721 TI - Correction. AB - In the article by Burke et al, "Current Science on Consumer Use of Mobile Health for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association," which published ahead of print August 13, 2015, and appeared in the September 22, 2015, issue of the journal (Circulation. 2015;132:1157-1213. DOI: 10.1161/CIR.0000000000000232), several corrections were needed.1. On page 1203, in the first column, last paragraph, the second sentence read, "Because medication may be a component of the treatment, we also searched for meditation adherence." It has been changed to read, "Because medication may be a component of the treatment, we also searched for medication adherence." 2. On page 1204, in the second column, third complete paragraph, the second sentence read, "As with any other product that claims to improve health, groups will want to answers to certain questions...." It has been changed to read, "As with any other product that claims to improve health, groups will want answers to certain questions...."3. On page 1204, in the second column, last paragraph, the fourth sentence read, "However, the responsibility for generating evidence should not fall solely only on the product developers." It has been changed to read, "However, the responsibility for generating evidence should not fall solely on the product developers." These corrections have been made to the print version and to the current online version of the article, which is available at http://circ.ahajournals.org/content/132/12/1157.full PMID- 26553722 TI - Correction. AB - In the article by Howard et al, "Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial Events," which published online ahead of print September 8, 2015, and appears in the November 10, 2015 issue of the journal (Circulation. 2015;132:1805-1815. DOI: 110.1161/CIRCULATIONAHA.115.016424), a correction was needed. The copyright line should have read, "(c) 2015 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited." We regret the error. This correction has been made to the print version and to the current online version of the article, which is available at http://circ.ahajournals.org/content/132/19/1805.full PMID- 26553723 TI - A Comparison of Self-Report and Audiometric Measures of Hearing and Their Associations With Functional Outcomes in Older Adults. AB - OBJECTIVE: The aim was to investigate whether associations of hearing impairment (HI) with functional outcomes in older adults differ when using self-report versus pure-tone audiometry. METHOD: We examined 1,669 participants >=70 years in National Health and Examination Survey from 2005-2006 and 2009-2010 whose hearing was assessed by self-report and pure-tone audiometry. We explored functional outcomes associated with audiometric HI (low physical activity, poor physical functioning, and hospitalization). RESULTS: In adjusted models, we found significant associations of audiometric HI with both subjective and objective outcomes (e.g., dichotomous HI with self-reported difficulty in activities of daily living [ADLs], odds ratio [OR] = 1.47, 95% confidence interval [CI] [1.05, 2.06], and low accelerometer-measured physical activity, OR = 2.19, 95% CI [1.11, 4.34]). In contrast, self-reported HI was only associated with subjective outcomes and not with objective outcomes (e.g., dichotomous HI with difficulty in ADLs, OR = 1.63, 95% CI [1.12, 2.38], and low accelerometer-measured physical activity, OR = 0.95, 95% CI [0.66, 1.35]). DISCUSSION: Results using self reported hearing should not be considered representative of results using audiometry and may provide distinct aspects of HI in older adults. PMID- 26553724 TI - Growing Old Behind Bars: Health Profiles of the Older Male Inmate Population in the United States. AB - OBJECTIVE: This study examines patterns of multimorbidity among elderly male inmates across four domains of health (chronic medical conditions, drug- and alcohol-related diseases, impairments, and mental and behavioral health) to understand the complex health care needs of this growing population. METHOD: We use the 2004 Survey of Inmates in State Correctional Facilities and Latent Class Regression Analysis to examine 22 health problems among 1,026 men aged 50 and older. RESULTS: There are four groups of elderly male inmates: (a) relatively healthy (45.1%), (b) substance users with behavioral health issues (23.4%), (c) chronic unhealthy with impairments and violence/injury (23.6%), and (d) very unhealthy across all domains (7.9%). These groups have unique sociodemographic background and incarceration history characteristics. CONCLUSION: This study demonstrates the complexity of health for elderly inmates. Prison health should continue to be monitored to aid correctional and community health programs in understanding clinical risks, exposures, and health care needs for this population. PMID- 26553725 TI - Steroid sulfatase activity in subcutaneous and visceral adipose tissue: a comparison between pre- and postmenopausal women. AB - OBJECTIVE: Adipose tissue is an important extragonadal site for steroid hormone biosynthesis. After menopause, estrogens are synthesized exclusively in peripheral tissues from circulating steroid precursors, of which the most abundant is dehydroepiandrosterone sulfate (DHEAS). Our aim was to study activity of steroid sulfatase, an enzyme hydrolyzing DHEAS, and expression of steroid converting enzyme genes in subcutaneous and visceral adipose tissue derived from pre- and postmenopausal women. DESIGN: Serum and paired abdominal subcutaneous and visceral adipose tissue samples were obtained from 18 premenopausal and seven postmenopausal women undergoing elective surgery for non-malignant reasons in Helsinki University Central Hospital. METHODS: To assess steroid sulfatase activity, radiolabeled DHEAS was incubated in the presence of adipose tissue homogenate and the liberated dehydroepiandrosterone (DHEA) was measured. Gene mRNA expressions were analyzed by quantitative RT-PCR. Serum DHEAS, DHEA, and estrogen concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Steroid sulfatase activity was higher in postmenopausal compared to premenopausal women in subcutaneous (median 379 vs 257 pmol/kg tissue per hour; P=0.006) and visceral (545 vs 360 pmol/kg per hour; P=0.004) adipose tissue. Visceral fat showed higher sulfatase activity than subcutaneous fat in premenopausal (P=0.035) and all (P=0.010) women. The mRNA expression levels of two estradiol-producing enzymes, aromatase and 17beta-hydroxysteroid dehydrogenase type 12, were higher in postmenopausal than in premenopausal subcutaneous adipose tissue. CONCLUSIONS: Steroid sulfatase activity in adipose tissue was higher in postmenopausal than in premenopausal women suggesting that DHEAS, derived from the circulation, could be more efficiently utilized in postmenopausal adipose tissue for the formation of biologically active sex hormones. PMID- 26553726 TI - The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus. AB - The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets. PMID- 26553728 TI - Plaque disruption by coronary computed tomographic angiography in stable patients vs. acute coronary syndrome: a feasibility study. AB - AIMS: This study was designed to determine whether coronary CT angiography (CTA) can detect features of plaque disruption in clinically stable patients and to compare lesion prevalence and features between stable patients and those with acute coronary syndrome (ACS). METHODS: We retrospectively identified patients undergoing CTA, followed by invasive coronary angiography (ICA) within 60 days. Quantitative 3-vessel CTA lesion analysis was performed on all plaques >=25% stenosis to assess total plaque volume, low attenuation plaque (LAP, <50 HU) volume, and remodelling index. Plaques were qualitatively assessed for CTA features of disruption, including ulceration and intra-plaque dye penetration (IDP). ICA was employed as a reference standard for disruption. A total of 145 (94 ACS and 51 stable) patients were identified. By CTA, plaque disruption was evident in 77.7% of ACS cases. Although more common among those with ACS, CTA also detected plaque disruption in 37.3% of clinically stable patients (P < 0.0001). CONCLUSIONS: Clinically stable patients commonly manifest plaques with features of disruption as determined by CTA. Though the prevalence of plaque disruption is less than patients with ACS, these findings support the concept that some clinically stable patients may harbour 'silent' disrupted plaques. These findings may have implications for detection of 'at risk' plaques and patients. PMID- 26553729 TI - No full admission for tau to the exclusive prion club yet. PMID- 26553727 TI - A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc- Mediates Aglycemic Neuronal Cell Death. AB - The astrocyte cystine/glutamate antiporter (system xc(-)) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc(-) expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes--either cultured alone or with neurons--to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc(-) mediates aglycemic neuronal cell death. PMID- 26553730 TI - Familial SUNCT in mother and son. AB - BACKGROUND: Trigeminal autonomic cephalalgias comprise a heterogeneous group of lateralized headaches associated with ipsilateral autonomic symptoms. They are usually localized within the territory of one or more rami of the trigeminal nerve, but may be localized outside its cutaneous territory. Although these headaches are considered primary disorders, the evidence supporting their genetic nature is lacking, particularly concerning their neuralgic forms, with the exception of a familial case described partly based on a historical account. CASE REPORTS: We report on a mother and son with episodic, short-lasting, intense, paroxysmal headaches, with the same localization in the left retroauricular region, associated with prominent conjunctival injection and tearing, which are consistent with the diagnosis of SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing). DISCUSSION: These cases corroborate the existence of hereditary forms of this disorder, thus supporting its primary nature. PMID- 26553731 TI - General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review. AB - BACKGROUND: The Clinical Trials Subcommittee of the International Headache Society (IHS) recommends that a placebo arm is included in comparative randomised clinical trials (RCTs) of multiple prophylactic drugs due to the highly variable placebo response in migraine prophylaxis studies. The use of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying reports of RCTs. RESULTS: A placebo arm was used in <10% (three of 31) of prophylactic RCTs in migraine. In only 7.1% (two of 28) of the comparative RCTs without placebo was one drug superior to another drug. Thus in 26 RCTs, including one study requiring more than 75,000 patient days, no difference was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine-prophylactic agents. In order to benefit current and future patients, the current strong tendency to omit placebo-controls in these RCTs should be replaced by adherence to the guidelines of the IHS. PMID- 26553732 TI - Psoriasis and Smoking: A Systematic Literature Review and Meta-Analysis With Qualitative Analysis of Effect of Smoking on Psoriasis Severity. AB - BACKGROUND: Smoking has been associated with psoriasis prevalence and severity. OBJECTIVE: To evaluate prevalence of smoking in patients with psoriasis and to examine the relationship between smoking and psoriasis severity. METHODS: MEDLINE, EMBASE, and Cochrane databases (1960-2012) and conference proceedings (2010-2012) were systematically searched using keywords relevant to psoriasis and smoking. Controlled studies addressing psoriasis and smoking status were included. A meta-analysis for the relative risk of smoking in psoriasis patients was performed. RESULTS: Meta-analysis identified a significant association between smoking and psoriasis with a relative risk of 1.88 (95% CI, 1.66-2.13) for smoking in patients with psoriasis versus patients without psoriasis. Eight articles of 11 with data on smoking and psoriasis severity suggested that severity increases with smoking status. CONCLUSIONS: This literature review is in favor of a positive association between the prevalence of smoking and psoriasis as well as an association between smoking and severity of psoriasis. PMID- 26553733 TI - Intralesional Mycobacterium w Vaccine Versus Cryotherapy in Treatment of Refractory Extragenital Warts: A Randomized, Open-Label, Comparative Study. AB - BACKGROUND: Initial reports of immunotherapy using intralesional Mycobacterium w (Mw) vaccine have documented its useful role in treatment of genital and extragenital warts. OBJECTIVES: To compare the efficacy and safety of intralesional Mw vaccine versus cryotherapy in the treatment of refractory extragenital warts. METHODS: This was a prospective, randomized, comparative study of 66 patients. The outcome was assessed in terms of complete clearance of warts and change in Dermatology Life Quality Index (DLQI) score. RESULTS: Complete clearance of treated warts was seen in 66.7% (20/30) and 65.5% (19/29) of patients in the Mw and cryotherapy groups, respectively (P = .769). Clearance of distant warts was significantly (P = .004) high in the Mw group. Improvement in DLQI was greater in the Mw group. Both treatment modalities were well tolerated, and no major side effects occurred. CONCLUSIONS: Mw vaccine and cryotherapy are equally efficacious in treatment of refractory extragenital warts. Mw vaccine has an added advantage of clearance of distant warts. PMID- 26553734 TI - Pilot Study to Evaluate the Efficacy and Safety of Oral Tacrolimus in Adult Patients With Refractory Severe Plaque Psoriasis. AB - BACKGROUND: Tacrolimus, a congener of cyclosporine, has replaced cyclosporine as a first-line treatment for most transplant patients due to its superior efficacy and safety. Tacrolimus has not been extensively studied for the treatment of psoriasis. OBJECTIVES: To study the efficacy and safety of oral tacrolimus in adult patients with severe refractory plaque psoriasis. METHODS: This was an open label pilot study. Patients with severe plaque type psoriasis who were unresponsive to at least 1 systemic treatment were treated with oral tacrolimus. RESULTS: Thirty patients were treated. After 12 weeks, improvement in mean Psoriasis Area Severity Index (PASI) score was 80.37% (P < .001), PASI 75 was observed in 19 of 26 (73.1%) patients, and PASI 90 was observed in 11 of 26 (42.3%) patients. No severe side effects were noted. CONCLUSION: Oral tacrolimus is an effective and safe option for the short-term treatment of severe plaque psoriasis. PMID- 26553735 TI - From Late-Onset Stress Symptomatology to Later-Adulthood Trauma Reengagement in Aging Combat Veterans: Taking a Broader View. AB - About a decade ago we proposed the notion of late-onset stress symptomatology, to characterize the later-life emergence of symptoms related to early-life warzone trauma among aging combat Veterans. We hypothesized that aging-related challenges (role transition and loss, death of family members and friends, physical and cognitive decline) might lead to increased reminiscence, and possibly distress, among Veterans who had previously dealt successfully with earlier traumatic events. Recently, we have reexamined our earlier ideas, to better reflect our developing understanding of this phenomenon, and to incorporate more contemporary perspectives on posttraumatic growth and resilience. As a result, we have broadened our conceptualization to later-adulthood trauma reengagement (LATR). We suggest that in later life many combat Veterans confront and rework their wartime memories in an effort to find meaning and build coherence. Through reminiscence, life review, and wrestling with issues such as integrity versus despair, they intentionally reengage with experiences they avoided or managed successfully earlier in life, perhaps without resolution or integration. This article links LATR to classic gerontologic notions, and elaborates how the LATR process can lead positively to personal growth or negatively to increased symptomatology. We also address the role of preventive intervention in enhancing positive outcomes for Veterans who reengage with their wartime memories in later life. PMID- 26553736 TI - African Americans and Clinical Research: Evidence Concerning Barriers and Facilitators to Participation and Recruitment Recommendations. AB - Purpose of the Study: The goal of the study was to examine barriers and facilitators to clinical research participation among African Americans, as well as recommendations for overcoming these. Design and Methods: Eight focus groups were conducted consisting of 64 individuals. These focus groups targeted 2 groups of individuals: (a) community members, including both individuals involved in research and individuals not involved in research, and (b) community leaders, including clergy, community health care providers and service providers who may influence decisions to participate in research. Results: Among participants in both groups, the most common barriers to participation included fear and mistrust of research due to multiple factors, such as a lack of information about research and prevailing knowledge of historical occurrences. Facilitators to research participation included intrinsic factors, such as a desire to help others, and extrinsic factors, such as familiarity with the research recruiter. The focus groups also directly engaged participants in discussions of strategies that might improve recruitment, such as the importance of providing personal stories that enable community members to understand the potential benefits of research. Implications: Findings from these focus groups address the mandate from funding agencies that emphasize the importance of including racially diverse populations in clinical research studies, and offer potential solutions for increasing the recruitment and retention of minority participants. PMID- 26553737 TI - Aging in Italy: The Need for New Welfare Strategies in an Old Country. AB - Italy, a Southern European country with 60.8 million inhabitants, has the largest proportion of elderly citizens (aged >=65) in Europe of 21.4%. The aging of the population is due to a number of reasons, such as baby boomers growing old, an increase in longevity, and low birth rate. Although international migration has increased in recent years, the addition of a foreign segment of the population has neither compensated for nor significantly curtailed the aging phenomenon. The impact of aging on the economic sustainability concerns the progressive reduction of the workforce, high incidence of pension spending in the overall resources allocated to welfare, recent reform of the pension system, and the growing issue of "non-self-sufficiency" in the elderly. Despite limited financial measures dedicated to research, Italy is conducting important studies on aging, both at the national and international level. Physicians and researchers in the field of geriatrics and gerontology are not only promoting quality of life in the elderly, and healthy-active aging, but also contributing to economic stability and social organization. Finally, nutritional and lifestyle habits-and their role in preventing chronic diseases-are the focus of the current international event EXPO 2015, with many sections dedicated to the elderly. PMID- 26553738 TI - Aging in Multi-ethnic Malaysia. AB - Multiethnic Malaysia provides a unique case study of divergence in population aging of different sociocultural subgroups within a country. Malaysia represents 3 major ethnicities in Asia-the Malay, Chinese, and Indian. The 3 ethnic groups are at different stages of population aging, as they have undergone demographic transition at different pace amidst rapid social and economic changes. Between 1991 and 2010, the Malaysian population aged 60 and over has more than doubled from about 1 million to 2.2 million, and this is projected to rise to about 7 million or 17.6% of the projected population of 40 million by 2040. In 2010, the aging index ranged from 22.8% among the Bumiputera (Malays and other indigenous groups), to 31.4% among the Indians and 55.0% among the Chinese. Population aging provides great challenges for Malaysia's social and economic development. The increasing prevalence of noncommunicable diseases in older adults, coupled with the erosion of the traditional family support system has increased demands on health care services with an overwhelming need for multidisciplinary and specialized geriatric care. Following the adoption of the National Policy for the Elderly in 1995, issues of population aging have gained increasing attention, especially among researchers. There is an urgent need to increase public awareness, develop infrastructure, as well as support action oriented research that will directly translate to comprehensive and cohesive social strategies, policies, and legislation to protect not just the current older Malaysians but the future of all Malaysians. PMID- 26553739 TI - A bleeding umbilical mass. PMID- 26553740 TI - A sinemydid turtle from the Jehol Biota provides insights into the basal divergence of crown turtles. AB - Morphological phylogenies stand in a major conflict with molecular hypotheses regarding the phylogeny of Cryptodira, the most diverse and widely distributed clade of extant turtles. However, molecular hypotheses are often considered a better estimate of phylogeny given that it is more consistent with the stratigraphic and geographic distribution of extinct taxa. That morphology fails to reproduce the molecular topology partly originates from problematic character polarization due to yet another contradiction around the composition of the cryptodiran stem lineage. Extinct sinemydids are one of these problematic clades: they have been either placed among stem-cryptodires, stem-chelonioid sea turtles, or even stem-turtles. A new sinemydid from the Early Cretaceous Jehol Biota (Yixian Formation, Barremian-Early Aptian) of China, Xiaochelys ningchengensis gen. et sp. nov., allows for a reassessment of the phylogenetic position of Sinemydidae. Our analysis indicates that sinemydids mostly share symplesiomorphies with sea turtles and their purported placement outside the crown-group of turtles is an artefact of previous datasets. The best current phylogenetic estimate is therefore that sinemydids are part of the stem lineage of Cryptodira together with an array of other Jurassic to Cretaceous taxa. Our study further emphasises the importance of using molecular scaffolds in global turtle analyses. PMID- 26553742 TI - Dissipative solitons and backfiring in the electrooxidation of CO on Pt. AB - Collisions of excitation pulses in dissipative systems lead usually to their annihilation. In this paper, we report electrochemical experiments exhibiting more complex pulse interaction with collision survival and pulse splitting, phenomena that have rarely been observed experimentally and are only poorly understood theoretically. Using spatially resolved in-situ Fourier transform infrared spectroscopy (FTIR) in the attenuated total reflection configuration, we monitored reaction pulses during the electrochemical oxidation of CO on Pt thin film electrodes in a flow cell. The system forms quasi-1d pulses that align parallel to the flow and propagate perpendicular to it. The pulses split once in a while, generating a second solitary wave in the backward moving direction. Upon collision, the waves penetrate each other in a soliton-like manner. These unusual pulse dynamics could be reproduced with a 3-component reaction-diffusion migration model with two inhibitor species, one of them exhibiting a long-range spatial coupling. The simulations shed light on existence criteria of such dissipative solitons. PMID- 26553741 TI - Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model. AB - Mutated disrupted in schizophrenia 1 (DISC1), a microtubule regulating protein, leads to schizophrenia and other psychiatric illnesses. It is hypothesized that microtubule stabilization may provide neuroprotection in schizophrenia. The NAP (NAPVSIPQ) sequence of activity-dependent neuroprotective protein (ADNP) contains the SxIP motif, microtubule end binding (EB) protein target, which is critical for microtubule dynamics leading to synaptic plasticity and neuroprotection. Bioinformatics prediction for FDA approved drugs mimicking SxIP-like motif which displace NAP-EB binding identified Risperidone. Risperidone or NAP effectively ameliorated object recognition deficits in the mutated DISC1 mouse model. NAP but not Risperidone, reduced anxiety in the mutated mice. Doxycycline, which blocked the expression of the mutated DISC1, did not reverse the phenotype. Transcripts of Forkhead-BOX P2 (Foxp2), a gene regulating DISC1 and associated with human ability to acquire a spoken language, were increased in the hippocampus of the DISC1 mutated mice and were significantly lowered after treatment with NAP, Risperidone, or the combination of both. Thus, the combination of NAP and standard of care Risperidone in humans may protect against language disturbances associated with negative and cognitive impairments in schizophrenia. PMID- 26553743 TI - Immuno-analysis of microparticles: probing at the limits of detection. AB - Microparticle (MP) research is clouded by debate regarding the accuracy and validity of flow cytometry (FCM) as an analytical methodology, as it is influenced by many variables including the pre-analytical conditions, instruments physical capabilities and detection parameters. This study utilises a simplistic in vitro system for generating MP, and through comparative analysis with immuno electron microscopy (Immuno-EM) assesses the strengths and limitations of probe selection and high-sensitivity FCM. Of the markers examined, MP were most specifically labelled with phosphatidylserine ligands, annexin V and lactadherin, although only ~60% MP are PS positive. Whilst these two ligands detect comparable absolute MP numbers, they interact with the same population in distinct manners; annexin V binding is enhanced on TNF induced MP. CD105 and CD54 expression were, as expected, consistent and enhanced following TNF activation respectively. Their labelling however accounted for as few as 30-40% of MP. The greatest discrepancies between FCM and I-EM were observed in the population solely labelled for the surface antigen. These findings demonstrate that despite significant improvements in resolution, high-sensitivity FCM remains limited in detecting small-size MP expressing low antigen levels. This study highlights factors to consider when selecting endothelial MP probes, as well as interpreting and representing data. PMID- 26553745 TI - Long-Term Treatment of Chronic Neuropathic Pain Using External Noninvasive External Peripheral Nerve Stimulation in Five Patients. AB - BACKGROUND: External noninvasive peripheral nerve stimulation (EN-PNS) is a neuromodulation technique in which a low-frequency electrical stimulation is applied via a ball-shaped electrode that is placed directly onto the skin. OBJECTIVES: To examine how this modality is being used in the long term, by patients with chronic neuropathic pain who had responded to this treatment in a short-term trial. MATERIALS AND METHODS: All patients with a diagnosis of neuropathic pain who had obtained a machine for continued long-term use (via special funding requests), following a successful trial between 2009 and 2012 were contacted. A successful trial was considered as >50% pain reduction, duration of any beneficial treatment effect >=12 hours, and improvements to function/reduced medication use. Data were collected from case notes and a telephone interview. RESULTS: Thirteen trials were recorded successful, out of 21 conducted. Eleven individual funding applications were made, of which seven were successful. Five patients were contactable. All reported continued stimulator use at follow-up (average = 3.5 years) and ongoing pain relief associated with treatment. Pain intensities (numerical rating scale 0-10) had reduced in all five cases when baseline scores were compared with follow-up scores; average pain 5.6 3.5 and worst pain 8.6-4.8. All patients reported a reduction in frequency of pain flare-ups during device use. CONCLUSION: Patients reported EN-PNS to provide ongoing benefit at long-term follow-up. Further prospective investigations are justified. PMID- 26553744 TI - Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. AB - BACKGROUND: Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. METHODS AND RESULTS: We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55+/-9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21+/-11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36+/-12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction >=50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). CONCLUSIONS: Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573. PMID- 26553746 TI - Inorganic-organic solar cells based on quaternary sulfide as absorber materials. AB - We report a novel promising quaternary sulfide (CuAgInS) to serve as a semiconductor sensitizer material in the photoelectrochemical field. In this study, CuAgInS (CAIS) sulfide sensitized ZnO nanorods were fabricated on ITO substrates through a facile and low-cost hydrothermal chemical method and applied on photoanodes for solar cells for the first time. The component and stoichiometry were key factors in determining the photoelectric performance of CAIS sulfide, which were controlled by modulating their reaction time. ZnO/Cu0.7Ag0.3InS2 nanoarrays exhibit an enhanced optical and photoelectric performance and the power conversion efficiency of ITO/ZnO/Cu0.7Ag0.3InS2/P3HT/Pt solid-state solar cell was up to 1.80%. The remarkable performance stems from improved electron transfer, a higher efficiency of light-harvesting and appropriate band gap alignment at the interface of the ZnO/Cu0.7Ag0.3InS2 NTs. The research indicates that CAIS as an absorbing material has enormous potential in solar cell systems. PMID- 26553747 TI - Sequential brief neuropsychological evaluation of migraineurs is identical to controls. AB - BACKGROUND: Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine. OBJECTIVE: To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications. METHOD: Assembly of the battery that was then applied twice within 6 weeks to interictal migraineurs and matched healthy controls. RESULTS: Migraine patients (n = 24) and controls (n = 24) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P = 0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores. CONCLUSIONS: Interictal migraineurs and controls performance is identical in a brief cognitive battery focused on executive functions. Repeated applications produced a practice effect that was quantified. PMID- 26553748 TI - Use of single-representative reverse-engineered surface-models for RSA does not affect measurement accuracy and precision. AB - Implant migration can be accurately quantified by model-based Roentgen stereophotogrammetric analysis (RSA), using an implant surface model to locate the implant relative to the bone. In a clinical situation, a single reverse engineering (RE) model for each implant type and size is used. It is unclear to what extent the accuracy and precision of migration measurement is affected by implant manufacturing variability unaccounted for by a single representative model. Individual RE models were generated for five short-stem hip implants of the same type and size. Two phantom analyses and one clinical analysis were performed: "Accuracy-matched models": one stem was assessed, and the results from the original RE model were compared with randomly selected models. "Accuracy random model": each of the five stems was assessed and analyzed using one randomly selected RE model. "Precision-clinical setting": implant migration was calculated for eight patients, and all five available RE models were applied to each case. For the two phantom experiments, the 95%CI of the bias ranged from 0.28 mm to 0.30 mm for translation and -2.3 degrees to 2.5 degrees for rotation. In the clinical setting, precision is less than 0.5 mm and 1.2 degrees for translation and rotation, respectively, except for rotations about the proximodistal axis (<4.1 degrees ). High accuracy and precision of model-based RSA can be achieved and are not biased by using a single representative RE model. At least for implants similar in shape to the investigated short-stem, individual models are not necessary. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:903-910, 2016. PMID- 26553749 TI - Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer. AB - PURPOSE: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men. EXPERIMENTAL DESIGN: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade-matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored. RESULTS: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo CONCLUSIONS: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. PMID- 26553750 TI - Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation. AB - Mutations in mitochondrial IDH2, one of the three isoforms of IDH, were discovered in patients with gliomas in 2009 and subsequently described in acute myelogenous leukemia (AML), angioimmunoblastic T-cell lymphoma, chondrosarcoma, and intrahepatic chloangiocarcinoma. The effects of mutations in IDH2 on cellular metabolism, the epigenetic state of mutated cells, and cellular differentiation have been elucidated in vitro and in vivo. Mutations in IDH2 lead to an enzymatic gain of function that catalyzes the conversion of alpha-ketoglutarate to beta hydroxyglutarate (2-HG). Supranormal levels of 2-HG lead to hypermethylation of epigenetic targets and a subsequent block in cellular differentiation. AG-221, a small-molecule inhibitor of mutant IDH2, is being explored in a phase I clinical trial for the treatment of AML, other myeloid malignancies, solid tumors, and gliomas. PMID- 26553751 TI - Distal esophageal spasm and the Chicago classification: is timing everything? AB - BACKGROUND: According to the Chicago classification of esophageal motility disorders, distal esophageal spasm (DES) is defined as premature esophageal contractions (distal latency [DL] <4.5 s) for >=20% of swallows, in the presence of a normal mean integral relaxation pressure (IRP). However, some patients with symptoms of DES have rapid contractions with a normal DL. The aim of this study was to characterize these patients and compare their clinical characteristics to those of patients classified as DES. METHODS: We retrospectively compared clinical characteristics and high-resolution manometry findings of patients with rapid contractions with normal latency to those meeting the Chicago classification criteria for DES. KEY RESULTS: Over a 3-year period, nine patients were diagnosed with DES and 14 showed rapid contractions in the distal esophagus with normal latency. The latter were younger than DES patients (60 +/- 4 vs 72 +/ 3 years, p < 0.05). Dysphagia and retrosternal pain occurred to a similar degree in both groups. Weight loss and abnormal barium esophagogram tended to be more frequent in DES patients. There was no difference in contractile front velocity (CFV) and in distal contractile integral (DCI) between patients with DES and rapid contractions with normal latency. Lower esophageal sphincter pressures were not different between groups. However, IRP was significantly higher in DES compared to rapid contractions with normal latency (11.7 +/- 0.6 mmHg vs 7.6 +/- 1.2 mmHg, p < 0.05), albeit still within the normal range. CONCLUSIONS & INFERENCES: These data suggest that patients with simultaneous contractions with normal latency represent a group of patients with many features similar to DES. PMID- 26553752 TI - Switchable Fe/Co Prussian blue networks and molecular analogues. AB - With the long term objective to build the next generation of devices from the molecular scale, scientists have explored extensively in the past two decades the Prussian blue derivatives and their remarkable physico-chemical properties. In particular, the exquisite Fe/Co system displays tuneable optical and magnetic behaviours associated with thermally and photo-induced metal-to-metal electron transfer processes. Recently, numerous research groups have been involved in the transfer of these electronic properties to new Fe/Co coordination networks of lower dimensionality as well as soluble molecular analogues in order to facilitate their manipulation and integration into devices. In this review, the most representative examples of tridimensional Fe/Co Prussian blue compounds are described, focusing on the techniques used to understand their photomagnetic properties. Subsequently, the different strategies employed toward the design of new low dimensional Prussian blue analogues based on a rational molecular building block approach are discussed emphasizing the advantages of these functional molecular systems. PMID- 26553753 TI - Radical [1,3] Rearrangements of Breslow Intermediates. AB - Breslow intermediates that bear radical-stabilizing N substituents, such as benzyl, cinnamyl, and diarylmethyl, undergo facile homolytic C-N bond scission under mild conditions to give products of formal [1,3] rearrangement rather than benzoin condensation. EPR experiments and computational analysis support a radical-based mechanism. Implications for thiamine-based enzymes are discussed. PMID- 26553754 TI - Pharmacotherapy and generic health-related quality of life in Parkinson's disease. AB - OBJECTIVES: Improvement of health-related quality of life (HRQoL) is one of the primary objectives of symptomatic therapies in Parkinson's disease (PD). The aim of this observational study was to investigate possible changes in generic HRQoL in relation to changed PD pharmacotherapy in the clinical setting. MATERIALS & METHODS: A total of 219 outpatients with mild to moderate PD (median H&Y score = 2.0), treated with oral antiparkinsonian medications, were investigated twice with a 6-month interval. At baseline, PD medication dose was increased for 82 patients for clinical reasons (median increase of 100 mg levodopa equivalent daily dose or 31.9%), whereas medication remained unchanged for 137 patients. Two generic HRQoL questionnaires, EQ-5D and 15D, were used at baseline and at 6 months, and the baseline and delta HRQoL values were compared between the treatment groups. RESULTS: In the entire sample, the EQ-VAS score decreased during the study period, indicating a general decline in HRQoL (P = 0.04). There were no differences in the baseline HRQoL values or delta values between the treatment groups as measured with EQ-5D or 15D (levodopa dose elevated vs dopamine agonist/MAO-B inhibitor dose elevated vs no change in medication). CONCLUSIONS: An approximately 1/3 increase in antiparkinsonian medication dose did not have an impact on generic HRQoL. Disease-specific QoL may be more sensitive to pharmacotherapy-related changes in PD. PMID- 26553755 TI - A Peptidyl-Transesterifying Type I Thioesterase in Salinamide Biosynthesis. AB - Salinamide A belongs to a rare class of bicyclic depsipeptide antibiotics in which the installation of a (4-methylhexa-2,4-dienoyl)glycine handle across a hexadepsipeptide core contributes to its chemical complexity and biological properties. Herein, we report the genetic and biochemical basis for salinamide construction in the marine bacterium Streptomyces sp. CNB-091, which involves a novel intermolecular transesterification reaction catalyzed by a type I thioesterase. Heterologous expression studies revealed the central role of the nonribosomal peptide synthetase Sln9 in constructing and installing the distinctive acylglycine "basket handle" of salinamide. Biochemical characterization of the Sln9 thioesterase domain established that transesterification of the serine residue of desmethylsalinamide E with acylated glycyl thioesters yields desmethylsalinamide C. PMID- 26553757 TI - Subthreshold vagal stimulation suppresses ventricular arrhythmia and inflammatory response in a canine model of acute cardiac ischaemia and reperfusion. AB - Subthreshold vagal stimulation (SVS) suppresses atrial arrhythmias in canine models and humans. This study was designed to examine whether SVS could decrease ventricular arrhythmia during ischaemia and reperfusion. Twenty-four anaesthetized dogs subjected to 1 h of coronary artery occlusion and 3 h of reperfusion were equally assigned into sham and SVS groups. Subthreshold vagal stimulation was initiated 15 min before coronary occlusion and maintained until the end of the reperfusion period using electrical stimulation on bilateral vagal trunks at 50% below the voltage which slowed the sinus rate. Ventricular arrhythmias were recorded during ischaemia and reperfusion periods. Serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), high-mobility group box 1 (HMGB1) and noradrenaline were detected at baseline, at the end of ischaemia and at the end of reperfusion. Area at risk and infarct size were evaluated after 3 h of reperfusion. Compared with the sham group, SVS significantly suppressed ischaemia- and reperfusion induced ventricular arrhythmias and decreased serum concentrations of CRP, IL-6, TNF-alpha, HMGB1 and noradrenaline during both the ischaemia period and the reperfusion period. However, SVS did not affect the area at risk, infarct size or the ratio of infarct size to area at risk. This study demonstrated that SVS exerted antiarrhythmic and anti-inflammatory effects in a canine model of ischaemia and reperfusion. PMID- 26553756 TI - Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes. AB - Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring "bystander" cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a "find-me" signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-kappaB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7 R in ATP release; thus, we examined P2X7 R-deficient mice and WT mice treated with P2X7 R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7 RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X7 RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7 R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. PMID- 26553759 TI - At Last: Getting Paid to Think! PMID- 26553758 TI - How to measure snoring? A comparison of the microphone, cannula and piezoelectric sensor. AB - The objective of this study was to compare to each other the methods currently recommended by the American Academy of Sleep Medicine (AASM) to measure snoring: an acoustic sensor, a piezoelectric sensor and a nasal pressure transducer (cannula). Ten subjects reporting habitual snoring were included in the study, performed at Landspitali-University Hospital, Iceland. Snoring was assessed by listening to the air medium microphone located on a patient's chest, compared to listening to two overhead air medium microphones (stereo) and manual scoring of a piezoelectric sensor and nasal cannula vibrations. The chest audio picked up the highest number of snore events of the different snore sensors. The sensitivity and positive predictive value of scoring snore events from the different sensors was compared to the chest audio: overhead audio (0.78, 0.98), cannula (0.55, 0.67) and piezoelectric sensor (0.78, 0.92), respectively. The chest audio was capable of detecting snore events with lower volume and higher fundamental frequency than the other sensors. The 200 Hz sampling rate of the cannula and piezoelectric sensor was one of their limitations for detecting snore events. The different snore sensors do not measure snore events in the same manner. This lack of consistency will affect future research on the clinical significance of snoring. Standardization of objective snore measurements is therefore needed. Based on this paper, snore measurements should be audio-based and the use of the cannula as a snore sensor be discontinued, but the piezoelectric sensor could possibly be modified for improvement. PMID- 26553760 TI - Multidisciplinary Care: For the Sake of Our Patients. PMID- 26553761 TI - Buying In. PMID- 26553762 TI - Ewing Sarcoma in a Patient With Cowden Syndrome. AB - A 47-year-old woman, initially diagnosed in 1996 with Cowden syndrome (CS), PTEN mutant bilateral breast cancer, a thyroid nodule, and uterine fibroids, presented to UCLA in 2013 with Ewing sarcoma of the pelvic bone. Her treatment course included mastectomies, hysterectomy/oophorectomy, and total thyroid resection, and chemotherapy, radiation, and hemipelvectomy for Ewing sarcoma. This case report illustrates the unusual presentation of Ewing sarcoma in a patient with PTEN-mutant CS, the probable underlying molecular pathogenesis, long-term management, and therapeutic considerations. PMID- 26553763 TI - Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines. AB - The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes. PMID- 26553764 TI - NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys. AB - BACKGROUND: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. METHODS: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. RESULTS: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. CONCLUSIONS: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care. PMID- 26553765 TI - The Impact of Insurance Status on Tumor Characteristics and Treatment Selection in Contemporary Patients With Prostate Cancer. AB - BACKGROUND: Approximately 15% of the US population does not have health insurance. The objective of this study was to evaluate the impact of insurance status on tumor characteristics and treatment selection in patients with prostate cancer. MATERIALS AND METHODS: We identified 20,393 patients younger than 65 years with prostate cancer in the 2010-2011 SEER database. Multivariable logistic regression analysis tested the relationship between insurance status and 2 end points: (1) presenting with low-risk prostate cancer at diagnosis and (2) receiving local treatment of the prostate. Locally weighted scatterplot smoothing methods were used to graphically explore the interaction among insurance status, use of local treatment, and baseline risk of cancer recurrence. The latter was defined using the Stephenson nomogram and CAPRA score. RESULTS: Overall, 18,993 patients (93%) were insured, 849 (4.2%) had Medicaid coverage, and 551 (2.7%) were uninsured. At multivariable analysis, Medicaid coverage (odds ratio [OR], 0.67; 95% CI, 0.57, 0.80; P<.0001) and uninsured status (OR, 0.57; 95% CI, 0.46, 0.71; P<.0001) were independent predictors of a lower probability of presenting with low-risk disease. Likewise, Medicaid coverage (OR, 0.72; 95% CI, 0.60, 0.86; P=.0003) and uninsured status (OR, 0.45; 95% CI, 0.37, 0.55; P<.0001) were independent predictors of a lower probability of receiving local treatment. In uninsured patients, treatment disparities became more pronounced as the baseline cancer recurrence risk increased (10% in low-risk patients vs 20% in high-risk patients). CONCLUSIONS: Medicaid beneficiaries and uninsured patients are diagnosed with higher-risk disease and are undertreated. The latter is more accentuated for patients with high-risk prostate cancer. This may seriously compromise the survival of these individuals. PMID- 26553766 TI - Patterns of Chemotherapy Administration in High-Risk Soft Tissue Sarcoma and Impact on Overall Survival. AB - BACKGROUND: Conflicting data exist on the benefit of chemotherapy in the management of high-risk soft tissue sarcoma (STS). Use of chemotherapy may be dependent on patient, tumor, and facility characteristics. This study sought to identify these factors and compare survival between treatment groups. PATIENTS AND METHODS: Patients with stage III STS were identified from the National Cancer Data Base (NCDB) from 1998 to 2012. Multiple logistic regression analysis was used to determine factors that influenced the probability of receiving chemotherapy. In a subset of patients, we determined the relationship between chemotherapy use and overall survival, using Kaplan-Meier curves and Cox regression analysis with propensity score adjustment. We also examined the effect of chemotherapy by histologic subgroup using interaction models. RESULTS: A total of 16,370 patients were included (N=5,377 for survival analysis). Patients who were younger than 40 years; male; privately insured; earned a higher income; had no comorbidities; had synovial sarcoma, angiosarcoma or "other" histology; and whose tumors were high-grade, greater than 10 cm, or from the lower extremity were significantly more likely to receive chemotherapy. Median unadjusted overall survival (OS) in the nonchemotherapy and chemotherapy groups was 51.3 and 82.7 months, respectively (P<.001). On adjusted analysis, the survival benefit remained significant (hazard ratio [HR], 0.85; P=.004). The benefit was particularly strong in the undifferentiated pleomorphic sarcoma (UPS) group on adjustment, with a median OS of 49.1 and 77.8 months for nonchemotherapy versus chemotherapy, respectively (HR, 0.77; P=.02). CONCLUSIONS: In addition to expected tumor and patient factors, histology, location of primary tumor, and socioeconomic status are associated with receipt/nonreceipt of chemotherapy in stage III STS. Chemotherapy use was associated with improved OS in the overall population, and specifically in the UPS subgroup. PMID- 26553767 TI - Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices. AB - BACKGROUND: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival. METHODS: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (>=7 days in any cycle of the course), dose reductions (>= 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). RESULTS: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486-0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted. CONCLUSIONS: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens. PMID- 26553769 TI - Role of Immune Therapies for Myeloma. AB - Immune therapy has emerged as a promising area of cancer therapeutics based on its potential for tumor selectivity and targeting of chemotherapy-resistant clones. Allogeneic transplantation produces durable remissions in a subset of patients, albeit at the cost of graft- versus-host disease. Recent years have witnessed efforts to induce more selective immune responses via dendritic cell vaccines, autologous and engineered T-cell therapy, and immune checkpoint blockade. Optimizing these immunotherapeutic approaches, understanding how to best use them in combination, and determining how to integrate them with standard anti-myeloma therapy could provide the potential to alter the natural history of this disease. PMID- 26553770 TI - Is the Preoperative Setting an Appropriate Platform for Drug Approval in Breast Cancer? PMID- 26553772 TI - Validity and reliability of the Diagnostic Adaptive Behaviour Scale. AB - BACKGROUND: The Diagnostic Adaptive Behaviour Scale (DABS) is a new standardised adaptive behaviour measure that provides information for evaluating limitations in adaptive behaviour for the purpose of determining a diagnosis of intellectual disability. This article presents validity evidence and reliability data for the DABS. METHOD: Validity evidence was based on comparing DABS scores with scores obtained on the Vineland Adaptive Behaviour Scale, second edition. The stability of the test scores was measured using a test and retest, and inter-rater reliability was assessed by computing the inter-respondent concordance. RESULTS: The DABS convergent validity coefficients ranged from 0.70 to 0.84, while the test-retest reliability coefficients ranged from 0.78 to 0.95, and the inter rater concordance as measured by intraclass correlation coefficients ranged from 0.61 to 0.87. CONCLUSIONS: All obtained validity and reliability indicators were strong and comparable with the validity and reliability coefficients of the most commonly used adaptive behaviour instruments. These results and the advantages of the DABS for clinician and researcher use are discussed. PMID- 26553768 TI - Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology. AB - Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. PMID- 26553773 TI - Clinical Practice Patterns in Constrictive Pericarditis Patients With Heart Failure: A Retrospective Cohort Study Using a National Inpatient Database in Japan. AB - BACKGROUND: Previous studies on constrictive pericarditis (CP) mainly concerned patients undergoing pericardiectomy. The reported perioperative mortality of CP patients remained high. Data on medically treated CP patients without pericardiectomy have been scarce. HYPOTHESIS: Constrictive pericarditis patients with more comorbidities are less likely to undergo pericardiectomy. METHODS: Using the Diagnosis Procedure Combination database from 2007 to 2013, we retrospectively identified CP patients admitted with heart failure of New York Heart Association (NYHA) class II to IV. We compared clinical characteristics between patients treated with and without pericardiectomy. A multivariable logistic regression analysis was performed to assess the factors associated with likelihood of undergoing pericardiectomy. RESULTS: Of 855 eligible patients, 164 (19.2%) underwent pericardiectomy (surgery group) and 691 (80.8%) did not (no surgery group). The surgery group was younger (mean age, 65.0 years vs 70.3 years; P < 0.001) and more often male (81.7% vs 72.2%; P = 0.013) than the no surgery group. No significant difference was seen in NYHA class and Barthel Index between the groups, whereas the surgery group had a lower Charlson Comorbidity Index (CCI). Older age, female sex, and higher CCI were significantly associated with a lower likelihood of undergoing pericardiectomy. In the surgery group, 30 day postoperative mortality was significantly higher in patients who underwent cardiopulmonary bypass than in those who did not (11.3% vs 2.9%; P = 0.030). CONCLUSIONS: Patients' backgrounds were associated with the likelihood of undergoing pericardiectomy. Conservative medical therapy may be acceptable in CP patients with severe background and high preoperative need for cardiopulmonary bypass. PMID- 26553774 TI - Fungal identification using a Bayesian classifier and the Warcup training set of internal transcribed spacer sequences. AB - Fungi are key organisms in many ecological processes and communities. Rapid and low cost surveys of the fungal members of a community can be undertaken by isolating and sequencing a taxonomically informative genomic region, such as the ITS (internal transcribed spacer), from DNA extracted from a metagenomic sample, and then classifying these sequences to determine which organisms are present. This paper announces the availability of the Warcup ITS training set and shows how it can be used with the Ribosomal Database Project (RDP) Bayesian Classifier to rapidly and accurately identify fungi using ITS sequences. The classifications can be down to species level and use conventional literature-based mycological nomenclature and taxonomic assignments. PMID- 26553775 TI - Phytophthora species recovered from the Connecticut River Valley in Massachusetts, USA. AB - Little is currently known about the assemblage of Phytophthora species in northeastern North America, representing a gap in our understanding of species incidence. Therefore, Phytophthora species were surveyed at 20 sites in Massachusetts, with 16 occurring in the Connecticut River Valley. Many of the sampled waterways were adjacent to active agricultural lands, yet were buffered by mature floodplain forests composed of Acer, Platanus, Populus and Ulmus. Isolates were recovered with three types of baits (rhododendron leaves, pear, green pepper) in 2013 and water filtration in 2014. Overall, 457 isolates of Phytophthora were recovered and based on morphological characters and rDNA internal transcribed spacer (ITS), beta-tubulin (beta-tub) and cytochrome oxidase c subunit I (cox1) sequences, 18 taxa were identified, including three new species: P. taxon intercalaris, P. taxon caryae and P. taxon pocumtuck. In addition, 49 isolates representing five species of Phytopythium also were identified. Water filtration captured a greater number of taxa (18) compared to leaf and fruit baits (12). Of the three bait types rhododendron leaves yielded the greatest number of isolates and taxa, followed by pear and green pepper, respectively. Despite the proximity to agricultural lands, none of the Phytophthora species baited are considered serious pathogens of vegetable crops in the region. However, many of the recovered species are known woody plant pathogens, including four species in the P. citricola s.l. complex that were identified: P. plurivora, P. citricola III, P. pini and a putative novel species, referred to here as P. taxon caryae. An additional novel species, P. taxon pocumtuck, is a close relative of P. borealis based on cox1 sequences. The results illustrate a high level of Phytophthora species richness in the Connecticut River Valley and that major rivers can serve as a source of inoculum for pathogenic Phytophthora species in the northeast. PMID- 26553776 TI - Global diversity and phylogeny of the Phellinus igniarius complex (Hymenochaetales, Basidiomycota) with the description of five new species. AB - The Phellinus igniarius complex corresponds to Phellinus s.s., a well supported clade in the polyphyletic Phellinus s.l. studied worldwide. Recently a molecular phylogeny of this complex was performed for the European and North American species. In this study we expand the taxon samplings of the P. igniarius complex to include 59, seven and 12 additional collections originating from China, Czech Republic and USA, respectively. We generated 78 nuc rDNA ITS1-5.8S-ITS2 (ITS) and 42 translation elongation factor 1-alpha gene (tef1alpha) sequences. Based on the morphological and phylogenetic (combined ITS and tef1alpha dataset) analyses, Phellinus monticola, P. orientoasiaticus, P. padicola, P. parmastoi and P. pomaceoides are newly described and illustrated from China and USA. Phellinus pseudoigniarius is treated as a later synonym of P. igniarius, whereas Phellinus betulinus subsp. betulinus is accepted as P. betulinus. A total of 15 species are accepted in the P. igniarius complex worldwide. Of them, 10 species are distributed in eastern Asia, eight in Europe and six in North America. The taxonomy, phylogeny, host associations and geographic distributions of these 15 species are briefly discussed. PMID- 26553777 TI - Two new species of true morels from Newfoundland and Labrador: cosmopolitan Morchella eohespera and parochial M. laurentiana. AB - Morphological and molecular phylogenetic studies of true morels (Morchella) in the Canadian province of Newfoundland and Labrador resulted in the discovery of two undescribed species in the M. elata clade that we initially distinguished by the informal designations Mel-19 and Mel-36. The latter species, also collected in New Brunswick, Canada, is hitherto known only from the St Lawrence River Basin. Mel-36 is described here as a novel, phylogenetically distinct species, M. laurentiana. Before the discovery of Mel-19 in Newfoundland and Labrador, New Brunswick and Washington state it was only known from central China and central and northern Europe. Mel-19 is described here as a novel species, M. eohespera. PMID- 26553778 TI - Three new species of Physalacria from China, with a key to the Asian taxa. AB - Three new and one previously described species of Physalacria (Physalacriaceae, Agaricales) are reported from China. Specimens of two additional species described from Malaysia and North America were studied for comparison. Placements of these species were corroborated based on morphological observations and molecular evidence from partial sequences of the nuc rDNA internal transcribed spacer regions (ITS) and the 28S D1-D3 region, and genes for translation elongation factor 1-alpha (tef1alpha) and the second largest subunit of RNA polymerase II (rpb2). These new species of Physalacria distributed in subtropical China were found on rotten wood of broadleaf trees or bamboo and possess stipitate-capitate basidiomata with four-spored basidia, clamp connections and smooth, inamyloid basidiospores. To facilitate studies of the genus in Asia, a key is provided for all Physalacria species reported from this region. PMID- 26553779 TI - Unraveling the Inocybe praetervisa group through type studies and ITS data: Inocybe praetervisoides sp. nov. from the Mediterranean region. AB - Species in the Inocybe praetervisa group are characterized by producing nodulose to angular basidiospores and a bulbous, marginate, white stipe devoid of any pinkish to reddish tinge. Species delimitation problems and common misinterpretations in the I. praetervisa group have not yet been resolved through type studies and analysis of molecular data. This study seeks to clarify the taxonomy and nomenclature of species around I. praetervisa. Analyses of the nuc rDNA internal transcribed regions (ITS) recovered two major groups within the I. praetervisa group that can be separated on the basis of cystidial morphology. The study of three authentic and topotypic specimens in the Bresadola herbarium revealed that the name I. praetervisa has been misapplied often. The ITS region of one of the specimens was obtained, and this specimen is designated as epitype in support of a lectotype. Inocybe rivularis is demonstrated to be a later synonym of I. praetervisa, while Inocybe phaeocystidiosa is the correct name for the species most often misdetermined as I. praetervisa. Inocybe salicis-herbaceae and I. praetervisa var. flavofulvida are shown to be synonyms of I. phaeocystidiosa based on ITS sequence data from type collections. A new species sister to I. phaeocystidiosa with a Mediterranean distribution is described as I. praetervisoides. Cystidial morphology, distribution of caulocystidia, basidiospore morphology and ecology are shown to be the main diagnostic characters for separating the species. Inocybe praetervisa and I. phaeocystidiosa have a transoceanic distribution in Europe and North America, whereas I. praetervisoides so far is known only from the Mediterranean region. PMID- 26553780 TI - Prospective Clinical Study of Precision Oncology in Solid Tumors. AB - Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0 2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. PMID- 26553782 TI - Are Most Cancers Caused by Specific Risk Factors Acting on Tissues With High Underlying Stem Cell Divisions? AB - A recent paper by Tomasetti and Vogelstein demonstrated a high correlation coefficient of 0.81 between estimated lifetime normal renewing cell (stem cell) divisions among tissues in the body and the lifetime cancer risk in that organ. This finding has been interpreted frequently to suggest that if two-thirds of cancers arise primarily through normal proliferation then environmental and hereditary factors combined could explain only one-third of cancers. Yet, the pool of dividing stem cells is what risk factors act upon; it is unlikely that risk factors and proliferation act completely independently and are simply additive; thus, there is no constraint that stem cell proliferation and environmental/genetic attributable risk sum to 100%. The cancers illustrated to represent lifetime risk in the paper by Tomasetti and Vogelstein all implicitly incorporate risk factors common in the United States (example, obesity, physical inactivity, tobacco, alcohol, diet, infectious agents). In fact, there is little evidence that a cancer would exceed a substantial rate, such as greater than 1% lifetime risk, in the absence of an important risk factor. Relatively high rates of cancer (eg, > 1% lifetime risk) only seem to occur in organs when strong risk factors (example, 10- to 20-fold) are superimposed on relatively high stem cell division. In organs with low stem cell divisions, the lifetime cancer risk will typically be very low. The major types and most abundant cancers in a given population will arise from tissues that have relatively high stem cell division rates and that have a high prevalence of strong relevant risk factors. PMID- 26553781 TI - Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience From Cancer Therapy Evaluation Program of the National Cancer Institute. AB - BACKGROUND: Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time. METHODS: A retrospective analysis was performed on 711 adult AML patients enrolling in 45 phase I clinical trials supported by the Cancer Therapy Evaluation Program of the National Cancer Institute from 1986 to 2009. Changes in ORR and mortality rates for patients enrolled in 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009 were estimated with multivariable logistic regression models. All statistical tests were two-sided. RESULTS: There was a statistically significant increase in AML patients enrolling in phase I clinical trials over time (1986 to 1990: n = 61; 2006 to 2009: n = 256; P = .03). The ORR for the entire cohort was 15.4% (1986 to 1990: 8.9%, 1991 to 1995: 21.1%; 1996 to 2000: 7.0%; 2001 to 2005: 10.0%; 2006 to 2009: 22.6%), and it statistically significantly improved over time (P < .001). There was a statistically significant improvement in ORRs with novel agents in combination vs single agents (ORR = 22.8% vs 4.7%, respectively, odds ratio = 5.95, 95% confidence interval = 3.22 to 11.9, P < .001). The 60-day mortality rate for the entire cohort was 22.6%, but it statistically significantly improved over time (P = .009). CONCLUSIONS: There has been an encouraging increase in AML patients enrolling in phase I clinical studies over time. The improvement in ORRs appears to be partly because of the increase in combination trials and the inclusion of previously untreated poor-risk AML. Continued enrollment of AML patients in early phase clinical trials is vital for drug development and improvement in therapeutic outcomes. PMID- 26553783 TI - Evaluation of the bond strength of different adhesive agents to a resin-modified calcium silicate material (TheraCal LC). AB - This study evaluated the bond strength of different adhesive agents to TheraCal LC and mineral trioxide aggregate (MTA) and examined the morphologic changes of these materials with different surface treatments. A total of 120 specimens, 60 of MTA Angelus (AMTA), and 60 of TheraCal LC, were prepared and divided into six subgroups according to the adhesive agent used; these agents included Scotchbond Multipurpose, Clearfil SE Bond, Clearfil Protect Bond, Clearfil S3 Bond, OptiBond All-in-One, and G-aenial Bond. After application of adhesive agents, Filtek Z250 composite resin was placed onto the specimens. Shear bond strengths were measured using a universal testing machine, followed by examination of the fractured surfaces. The surface changes of the specimens were observed using scanning electron microscopy. Data were compared by two-way analysis of variance. Although no significant differences were found among the bond strengths of different adhesives to AMTA (p = 0.69), a significant difference was found in terms of bond strengths of different adhesives to the TheraCal LC surface (p < 0.001). The total-etch adhesive system more strongly bonded to TheraCal LC compared to the bond with other adhesives. TheraCal LC bonded significantly more strongly than AMTA regardless of the adhesive agents tested. Resin-modified calcium silicate showed higher bond strength than AMTA in terms of the composite bond to these materials with different bonding systems. On the other hand, the highest shear bond-strength values were found for composite bonds with the combination of TheraCal LC and the total-etch adhesive system. SCANNING 38:403-411, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26553784 TI - Foodomics: A new tool to differentiate between organic and conventional foods. AB - The demand for organic food is increasing annually due to the growing consumer trend for more natural products that have simpler ingredient lists, involve less processing and are grown free of pesticides. However, there is still not enough nutritional evidence in favor of organic food consumption. Classical chemical analysis of macro- and micronutrients has demonstrated that organic crops are poorer in nitrogen, but clear evidence for other nutrients is lacking. Omics technologies forming part of the new discipline of foodomics have allowed the detection of possible nutritional differences between organic and conventional production, although many results remain controversial and contradictory. The main focus of this review is to provide an overview of the studies that use foodomics techniques as a tool to differentiate between organic and conventional production. PMID- 26553785 TI - Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINT. AB - In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research. PMID- 26553787 TI - In Reply. PMID- 26553786 TI - Long-Term Outcomes and Risk Factors Associated With Acute Encephalitis in Children. AB - Background: Factors associated with poor outcomes of children with encephalitis are not well known. We sought to determine whether electroencephalography (EEG) findings, magnetic resonance imaging (MRI) abnormalities, or the presence of seizures at presentation were associated with poor outcomes. Methods: A retrospective review of patients aged 0 to 21 years who met criteria for a diagnosis of encephalitis admitted between 2000 and 2010 was conducted. Parents of eligible children were contacted and completed 2 questionnaires that assessed current physical and emotional quality of life and neurological deficits at least 1 year after discharge. Results: During the study period, we identified 142 patients with an International Classification of Diseases 9th Revision diagnosis of meningitis, meningoencephalitis, or encephalitis. Of these patients, 114 met criteria for a diagnosis of encephalitis, and 76 of these patients (representing 77 hospitalizations) had complete data available. Forty-nine (64%) patients were available for follow-up. Patients admitted to the intensive care unit were more likely to have abnormal EEG results (P = .001). The presence of seizures on admission was associated with ongoing seizure disorder at follow-up. One or more years after hospitalization, 78% of the patients had persistent symptoms, including 35% with seizures. Four (5%) of the patients died. Abnormal MRI findings and the number of abnormal findings on initial presentation were associated with lower quality-of-life scores. Conclusions: Encephalitis leads to significant morbidity and death, and incomplete recovery is achieved in the majority of hospitalized patients. Abnormal EEG results were found more frequently in critically ill children, patients with abnormal MRI results had lower quality-of-life scores on follow-up, and the presence of seizures on admission was associated with ongoing seizure disorder and lower physical quality of-life scores. PMID- 26553788 TI - Detrimental Effects of Not Using International Reference Materials to Calibrate Cystatin C Assays. PMID- 26553789 TI - Is Rheumatoid Factor Really Associated with Deep Venous Thrombosis? PMID- 26553790 TI - Identification and Annotation of Lipid Species in Metabolomics Studies Need Improvement. PMID- 26553791 TI - US Food and Drug Administration Perspectives on Clinical Mass Spectrometry. AB - Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry based devices and enhance their entry into the clinic. PMID- 26553792 TI - In Reply. PMID- 26553793 TI - A Spectrum of Views on Clinical Mass Spectrometry. PMID- 26553794 TI - In Reply. PMID- 26553795 TI - Effective Use of Mass Spectrometry in the Clinical Laboratory. AB - BACKGROUND: Historically the success of mass spectrometry in the clinical laboratory has focused on drugs of abuse confirmations, newborn screening, and steroid analysis. Clinical applications of mass spectrometry continue to expand, and mass spectrometry is now being used in almost all areas of laboratory medicine. CONTENT: A brief background of the evolution of mass spectrometry in the clinical laboratory is provided with a discussion of future applications. Prominent examples of mass spectrometry are covered to illustrate how it has improved the practice of medicine and enabled physicians to provide better patient care. With increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing has been shown to provide cost-effective solutions. In addition to pointing out the numerous benefits, the challenges of implementing mass spectrometry in the clinical laboratory are also covered. SUMMARY: Mass spectrometry continues to play a prominent role in the field of laboratory medicine. The advancement of this technology along with the development of new applications will only accelerate the incorporation of mass spectrometry into more areas of medicine. PMID- 26553796 TI - A Matter of Choice: Opportunities and Obstacles Facing People with ESRD. AB - Kidney failure is an overwhelming, life-shattering event, but patients with ESRD do not see themselves as being at the end stage of their lives. On the contrary, patients opting for kidney dialysis are choosing to live. Ideally, then, public policy would support patients' choices about how to live-specifically, the choice to continue working. Many patients with ESRD faced with the limitations of their health status and the demands of their treatment understandably choose to leave their jobs, a choice that is facilitated by the availability of public disability and health insurance. However, other patients who have the desire and opportunity to continue working may not get the guidance and support that can actually make their employment possible. Specifically, current disability and health insurance may fail to provide timely treatment and employment counseling to help patients with ESRD remain in their jobs. We, therefore, propose that the Center for Medicare and Medicaid Services support ESRD Networks to initiate more timely employment and treatment counseling in both the ESRD and the late-stage pre-ESRD setting. Although it is too late to require such counseling in the new network scope of work for 2016-2020, active experimentation in the next few years can lay the groundwork for a subsequent contract. PMID- 26553798 TI - InterRNA: a database of base interactions in RNA structures. AB - A major component of RNA structure stabilization are the hydrogen bonded interactions between the base residues. The importance and biological relevance for large clusters of base interactions can be much more easily investigated when their occurrences have been systematically detected, catalogued and compared. In this paper, we describe the database InterRNA (INTERactions in RNA structures database-http://mfrlab.org/interrna/) that contains records of known RNA 3D motifs as well as records for clusters of bases that are interconnected by hydrogen bonds. The contents of the database were compiled from RNA structural annotations carried out by the NASSAM (http://mfrlab.org/grafss/nassam) and COGNAC (http://mfrlab.org/grafss/cognac) computer programs. An analysis of the database content and comparisons with the existing corpus of knowledge regarding RNA 3D motifs clearly show that InterRNA is able to provide an extension of the annotations for known motifs as well as able to provide novel interactions for further investigations. PMID- 26553797 TI - An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli. AB - Almost all free-living bacteria contain toxin-antitoxin (TA) systems on their genomes and the targets of toxins are highly diverse. Here, we found a novel, previously unidentified TA system in Escherichia coli named yjhX-yjhQ. Induction of YjhX (85 amino acid residues) causes cell-growth arrest resulting in cell death, while YjhQ (181 residues) co-induction resumes cell growth. The primary cellular target of YjhX was found to be topoisomerase I (TopA), inhibiting both DNA replication and RNA synthesis. Notably, YjhX has no homology to any other toxins of the TA systems. YjhX was expressed well with an N-terminal protein S (PrS) tag in soluble forms. PrS-YjhX specifically interacts with the N-terminal region of TopA (TopA67) but not full-TopA in the absence of plasmid DNA, while PrS-YjhX binds to full-TopA in the presence of DNA. Notably, YjhX does not directly interact with DNA and RNA. YjhX inhibits only topoisomerase I but not topoisomerase III and IV in vitro. Hence, yjhX is renamed as the gene for the TopA inhibitor (the topAI gene). TopAI is the first endogenous protein inhibitor specific for topoisomerase I. PMID- 26553799 TI - DASHR: database of small human noncoding RNAs. AB - Small non-coding RNAs (sncRNAs) are highly abundant RNAs, typically <100 nucleotides long, that act as key regulators of diverse cellular processes. Although thousands of sncRNA genes are known to exist in the human genome, no single database provides searchable, unified annotation, and expression information for full sncRNA transcripts and mature RNA products derived from these larger RNAs. Here, we present the Database of small human noncoding RNAs (DASHR). DASHR contains the most comprehensive information to date on human sncRNA genes and mature sncRNA products. DASHR provides a simple user interface for researchers to view sequence and secondary structure, compare expression levels, and evidence of specific processing across all sncRNA genes and mature sncRNA products in various human tissues. DASHR annotation and expression data covers all major classes of sncRNAs including microRNAs (miRNAs), Piwi interacting (piRNAs), small nuclear, nucleolar, cytoplasmic (sn-, sno-, scRNAs, respectively), transfer (tRNAs), and ribosomal RNAs (rRNAs). Currently, DASHR (v1.0) integrates 187 smRNA high-throughput sequencing (smRNA-seq) datasets with over 2.5 billion reads and annotation data from multiple public sources. DASHR contains annotations for ~ 48,000 human sncRNA genes and mature sncRNA products, 82% of which are expressed in one or more of the curated tissues. DASHR is available at http://lisanwanglab.org/DASHR. PMID- 26553801 TI - WITHDRAWN--a resource for withdrawn and discontinued drugs. AB - Post-marketing drug withdrawals can be associated with various events, ranging from safety issues such as reported deaths or severe side-effects, to a multitude of non-safety problems including lack of efficacy, manufacturing, regulatory or business issues. During the last century, the majority of drugs voluntarily withdrawn from the market or prohibited by regulatory agencies was reported to be related to adverse drug reactions. Understanding the underlying mechanisms of toxicity is of utmost importance for current and future drug discovery. Here, we present WITHDRAWN, a resource for withdrawn and discontinued drugs publicly accessible at http://cheminfo.charite.de/withdrawn. Today, the database comprises 578 withdrawn or discontinued drugs, their structures, important physico-chemical properties, protein targets and relevant signaling pathways. A special focus of the database lies on the drugs withdrawn due to adverse reactions and toxic effects. For approximately one half of the drugs in the database, safety issues were identified as the main reason for withdrawal. Withdrawal reasons were extracted from the literature and manually classified into toxicity types representing adverse effects on different organs. A special feature of the database is the presence of multiple search options which will allow systematic analyses of withdrawn drugs and their mechanisms of toxicity. PMID- 26553800 TI - Binding of 14-3-3 reader proteins to phosphorylated DNMT1 facilitates aberrant DNA methylation and gene expression. AB - Mammalian DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for maintenance methylation. Phosphorylation of Ser143 (pSer143) stabilizes DNMT1 during DNA replication. Here, we show 14-3-3 is a reader protein of DNMT1pSer143. In mammalian cells 14-3-3 colocalizes and binds DNMT1pSer143 post-DNA replication. The level of DNMT1pSer143 increased with overexpression of 14-3-3 and decreased by its depletion. Binding of 14-3-3 proteins with DNMT1pSer143 resulted in inhibition of DNA methylation activity in vitro. In addition, overexpression of 14-3-3 in NIH3T3 cells led to decrease in DNMT1 specific activity resulting in hypomethylation of the genome that was rescued by transfection of DNMT1. Genes representing cell migration, mobility, proliferation and focal adhesion pathway were hypomethylated and overexpressed. Furthermore, overexpression of 14-3-3 also resulted in enhanced cell invasion. Analysis of TCGA breast cancer patient data showed significant correlation for DNA hypomethylation and reduced patient survival with increased 14-3-3 expressions. Therefore, we suggest that 14-3-3 is a crucial reader of DNMT1pSer143 that regulates DNA methylation and altered gene expression that contributes to cell invasion. PMID- 26553802 TI - A dynamic checkpoint in oxidative lesion discrimination by formamidopyrimidine DNA glycosylase. AB - In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzymes cannot rely solely on interactions in the substrate-binding centre to achieve their exquisite specificity. It is widely believed that substrate recognition by such enzymes involves a series of conformational changes in the enzyme-DNA complex with sequential gates favoring cognate DNA and rejecting nonsubstrates. However, direct evidence for such mechanism is limited to a few systems. We report that discrimination between the oxidative DNA lesion, 8-oxoguanine (oxoG) and its normal counterpart, guanine, by the repair enzyme, formamidopyrimidine DNA glycosylase (Fpg), likely involves multiple gates. Fpg uses an aromatic wedge to open the Watson-Crick base pair and everts the lesion into its active site. We used molecular dynamics simulations to explore the eversion free energy landscapes of oxoG and G by Fpg, focusing on structural and energetic details of oxoG recognition. The resulting energy profiles, supported by biochemical analysis of site-directed mutants disturbing the interactions along the proposed path, show that Fpg selectively facilitates eversion of oxoG by stabilizing several intermediate states, helping the rapidly sliding enzyme avoid full extrusion of every encountered base for interrogation. Lesion recognition through multiple gating intermediates may be a common theme in DNA repair enzymes. PMID- 26553803 TI - Gramene 2016: comparative plant genomics and pathway resources. AB - Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ~ 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials. PMID- 26553805 TI - Multiplex pairwise assembly of array-derived DNA oligonucleotides. AB - While the cost of DNA sequencing has dropped by five orders of magnitude in the past decade, DNA synthesis remains expensive for many applications. Although DNA microarrays have decreased the cost of oligonucleotide synthesis, the use of array-synthesized oligos in practice is limited by short synthesis lengths, high synthesis error rates, low yield and the challenges of assembling long constructs from complex pools. Toward addressing these issues, we developed a protocol for multiplex pairwise assembly of oligos from array-synthesized oligonucleotide pools. To evaluate the method, we attempted to assemble up to 2271 targets ranging in length from 192-252 bases using pairs of array-synthesized oligos. Within sets of complexity ranging from 131-250 targets, we observed error-free assemblies for 90.5% of all targets. When all 2271 targets were assembled in one reaction, we observed error-free constructs for 70.6%. While the assembly method intrinsically increased accuracy to a small degree, we further increased accuracy by using a high throughput 'Dial-Out PCR' protocol, which combines Illumina sequencing with an in-house set of unique PCR tags to selectively amplify perfect assemblies from complex synthetic pools. This approach has broad applicability to DNA assembly and high-throughput functional screens. PMID- 26553804 TI - Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. AB - The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55,000 organisms (>4800 viruses, >40,000 prokaryotes and >10,000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management. PMID- 26553806 TI - A novel conceptual approach to read-filtering in high-throughput amplicon sequencing studies. AB - Adequate read filtering is critical when processing high-throughput data in marker-gene-based studies. Sequencing errors can cause the mis-clustering of otherwise similar reads, artificially increasing the number of retrieved Operational Taxonomic Units (OTUs) and therefore leading to the overestimation of microbial diversity. Sequencing errors will also result in OTUs that are not accurate reconstructions of the original biological sequences. Herein we present the Poisson binomial filtering algorithm (PBF), which minimizes both problems by calculating the error-probability distribution of a sequence from its quality scores. In order to validate our method, we quality-filtered 37 publicly available datasets obtained by sequencing mock and environmental microbial communities with the Roche 454, Illumina MiSeq and IonTorrent PGM platforms, and compared our results to those obtained with previous approaches such as the ones included in mothur, QIIME and USEARCH. Our algorithm retained substantially more reads than its predecessors, while resulting in fewer and more accurate OTUs. This improved sensitiveness produced more faithful representations, both quantitatively and qualitatively, of the true microbial diversity present in the studied samples. Furthermore, the method introduced in this work is computationally inexpensive and can be readily applied in conjunction with any existent analysis pipeline. PMID- 26553807 TI - Theoretical estimates of exposure timescales of protein binding sites on DNA regulated by nucleosome kinetics. AB - It is being increasingly realized that nucleosome organization on DNA crucially regulates DNA-protein interactions and the resulting gene expression. While the spatial character of the nucleosome positioning on DNA has been experimentally and theoretically studied extensively, the temporal character is poorly understood. Accounting for ATPase activity and DNA-sequence effects on nucleosome kinetics, we develop a theoretical method to estimate the time of continuous exposure of binding sites of non-histone proteins (e.g. transcription factors and TATA binding proteins) along any genome. Applying the method to Saccharomyces cerevisiae, we show that the exposure timescales are determined by cooperative dynamics of multiple nucleosomes, and their behavior is often different from expectations based on static nucleosome occupancy. Examining exposure times in the promoters of GAL1 and PHO5, we show that our theoretical predictions are consistent with known experiments. We apply our method genome-wide and discover huge gene-to-gene variability of mean exposure times of TATA boxes and patches adjacent to TSS (+1 nucleosome region); the resulting timescale distributions have non-exponential tails. PMID- 26553808 TI - Knockout of Drosophila RNase ZL impairs mitochondrial transcript processing, respiration and cell cycle progression. AB - RNase Z(L) is a highly conserved tRNA 3'-end processing endoribonuclease. Similar to its mammalian counterpart, Drosophila RNase Z(L) (dRNaseZ) has a mitochondria targeting signal (MTS) flanked by two methionines at the N-terminus. Alternative translation initiation yields two protein forms: the long one is mitochondrial, and the short one may localize in the nucleus or cytosol. Here, we have generated a mitochondria specific knockout of the dRNaseZ gene. In this in vivo model, cells deprived of dRNaseZ activity display impaired mitochondrial polycistronic transcript processing, increased reactive oxygen species (ROS) and a switch to aerobic glycolysis compensating for cellular ATP. Damaged mitochondria impose a cell cycle delay at the G2 phase disrupting cell proliferation without affecting cell viability. Antioxidants attenuate genotoxic stress and rescue cell proliferation, implying a critical role for ROS. We suggest that under a low stress condition, ROS activate tumor suppressor p53, which modulates cell cycle progression and promotes cell survival. Transcriptional profiling of p53 targets confirms upregulation of antioxidant and cycB-Cdk1 inhibitor genes without induction of apoptotic genes. This study implicates Drosophila RNase Z(L) in a novel retrograde signaling pathway initiated by the damage in mitochondria and manifested in a cell cycle delay before the mitotic entry. PMID- 26553809 TI - The Degradome database: expanding roles of mammalian proteases in life and disease. AB - Since the definition of the degradome as the complete repertoire of proteases in a given organism, the combined effort of numerous laboratories has greatly expanded our knowledge of its roles in biology and pathology. Once the genomic sequences of several important model organisms were made available, we presented the Degradome database containing the curated sets of known protease genes in human, chimpanzee, mouse and rat. Here, we describe the updated Degradome database, featuring 81 new protease genes and 7 new protease families. Notably, in this short time span, the number of known hereditary diseases caused by mutations in protease genes has increased from 77 to 119. This increase reflects the growing interest on the roles of the degradome in multiple diseases, including cancer and ageing. Finally, we have leveraged the widespread adoption of new webtools to provide interactive graphic views that show information about proteases in the global context of the degradome. The Degradome database can be accessed through its web interface at http://degradome.uniovi.es. PMID- 26553811 TI - PASS2 database for the structure-based sequence alignment of distantly related SCOP domain superfamilies: update to version 5 and added features. AB - Structure-based sequence alignment is an essential step in assessing and analysing the relationship of distantly related proteins. PASS2 is a database that records such alignments for protein domain superfamilies and has been constantly updated periodically. This update of the PASS2 version, named as PASS2.5, directly corresponds to the SCOPe 2.04 release. All SCOPe structural domains that share less than 40% sequence identity, as defined by the ASTRAL compendium of protein structures, are included. The current version includes 1977 superfamilies and has been assembled utilizing the structure-based sequence alignment protocol. Such an alignment is obtained initially through MATT, followed by a refinement through the COMPARER program. The JOY program has been used for structural annotations of such alignments. In this update, we have automated the protocol and focused on inclusion of new features such as mapping of GO terms, absolutely conserved residues among the domains in a superfamily and inclusion of PDBs, that are absent in SCOPe 2.04, using the HMM profiles from the alignments of the superfamily members and are provided as a separate list. We have also implemented a more user-friendly manner of data presentation and options for downloading more features. PASS2.5 version is available at http://caps.ncbs.res.in/pass2/. PMID- 26553810 TI - Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts. AB - High affinity antisense oligonucleotides (ASOs) containing bicylic modifications (BNA) such as locked nucleic acid (LNA) designed to induce target RNA cleavage have been shown to have enhanced potency along with a higher propensity to cause hepatotoxicity. In order to understand the mechanism of this hepatotoxicity, transcriptional profiles were collected from the livers of mice treated with a panel of highly efficacious hepatotoxic or non-hepatotoxic LNA ASOs. We observed highly selective transcript knockdown in mice treated with non-hepatotoxic LNA ASOs, while the levels of many unintended transcripts were reduced in mice treated with hepatotoxic LNA ASOs. This transcriptional signature was concurrent with on-target RNA reduction and preceded transaminitis. Remarkably, the mRNA transcripts commonly reduced by toxic LNA ASOs were generally not strongly associated with any particular biological process, cellular component or functional group. However, they tended to have much longer pre-mRNA transcripts. We also demonstrate that the off-target RNA knockdown and hepatotoxicity is attenuated by RNase H1 knockdown, and that this effect can be generalized to high affinity modifications beyond LNA. This suggests that for a certain set of ASOs containing high affinity modifications such as LNA, hepatotoxicity can occur as a result of unintended off-target RNase H1 dependent RNA degradation. PMID- 26553812 TI - Identification of beta-hydroxy fatty acid esters and primary, secondary alkanediol esters in cuticular waxes of the moss Funaria hygrometrica. AB - The plant cuticle, a multi-layered membrane that covers plant aerial surfaces to prevent desiccation, consists of the structural polymer cutin and surface-sealing waxes. Cuticular waxes are complex mixtures of ubiquitous, typically monofunctional fatty acid derivatives and taxon-specific, frequently bifunctional specialty compounds. To further our understanding of the chemical diversity of specialty compounds, the waxes on the aerial structures of the leafy gametophyte, sporophyte capsule, and calyptra of the moss Funaria hygrometrica were surveyed. Respective moss surfaces were extracted, and resulting lipid mixtures were analyzed by gas chromatography-mass spectrometry (GC-MS). The extracts contained ubiquitous wax compound classes along with two prominent, unidentified classes of compounds that exhibited some characteristics of bifunctional structures. Microscale transformations led to derivatives with characteristic MS fragmentation patterns suggesting possible structures for these compounds. To confirm the tentative structure assignments, one compound in each of the suspected homologous series was synthesized. Based on GC-MS comparison with the authentic standards, the first series of compounds was identified as containing esters formed by beta-hydroxy fatty acids and wax alcohols, with ester chain lengths varying from C42 to C50 and the most prominent homolog being C46. The second series consisted of fatty acid esters of 1,7-alkanediols, linked via the primary hydroxyl group, with ester chain lengths C40-C52 also dominated by the C46 homolog. The beta-hydroxy acid esters were restricted to the sporophyte capsule, and the diol esters to the leafy gametophyte and calyptra. Based on their homolog and isomer distributions, and the presence of free 1,7 triacontanediol, possible biosynthetic reactions leading to these compounds are discussed. PMID- 26553813 TI - [Brazilian consensus on anesthetic depth monitoring]. PMID- 26553814 TI - First record of Mesopithecus (Cercopithecidae, Colobinae) from the Miocene of the Iberian Peninsula. AB - We report dental remains of the extinct colobine monkey Mesopithecus from the Turolian (MN13, Late Miocene, ca. 6.23 Ma) locality of Venta del Moro (Valencia, Spain). They include most of the deciduous dentition and the unerupted germs of the first molars of a single infantile individual, as well as two lower left lateral incisors from two additional individuals. On the basis of morphometric comparisons, mainly based on the M1s, these remains are attributed to the Late Miocene species Mesopithecus pentelicus. They represent a significant addition to the knowledge of the deciduous dentition of this taxon, much less well-known than the permanent dentition. Although this genus was widely distributed from the Late Miocene through the Pliocene across Europe, southwestern Asia, Pakistan, and China, until now its occurence in the Late Miocene of the Iberian Peninsula had not been documented conclusively. Hence, the reported remains considerably enlarge southwestwards the known geographic distribution of Mesopithecus. The presence of this genus at Venta del Moro must be understood within the framework of the significant faunal turnover that took place in European faunas during the latest Turolian (the second Messinian mammalian dispersal), which is further documented at this locality by the occurrence of other eastern immigrants. At the same time, the presence of M. pentelicus at this site agrees well with previous paleoenvironmental and sedimentological evidence, indicating a lacustrine depositional environment with strong hydrologic seasonality. PMID- 26553815 TI - A new small pliopithecoid primate from the Middle Miocene of Thailand. AB - Pliopithecoids represent a monophyletic group of putative stem catarrhines whose evolutionary history is incompletely known. They have been recorded from Europe and Asia, between the late Early Miocene and the Late Miocene. Asian pliopithecoids are less well documented than their European counterparts, often being represented by a fragmentary fossil record. New discoveries are therefore critical to reconstruct the evolutionary history of the whole group. Here, we describe two isolated molars from Ban San Klang, a late Middle Miocene locality in northern Thailand, which confirms the presence of pliopithecoids in Southeast Asia. The lower molar had originally been described as being that of a dendropithecoid, but it was later recognized as pertaining to a pliopithecoid. The discovery, in the same locality, of an additional upper molar attributed to the same species confirms the pliopithecoid status of this taxon and highlights its distinctiveness with respect to other known Asian pliopithecoids. However, the mosaic of primitive and autapomorphic features characterizing this Thai fossil, as well as its limited anatomical representation, preclude us from assigning it to either of the known pliopithecid subfamilies. Nevertheless, it represents the only pliopithecoid in Southeast Asia and displays a mosaic of unique characters which emphasizes the peculiarity of that province, as suggested previously with respect to its hominoid primate. PMID- 26553816 TI - Morphology of the thoracolumbar spine of the middle Miocene hominoid Nacholapithecus kerioi from northern Kenya. AB - A new caudal thoracic and a new lumbar vertebra of Nacholapithecus kerioi, a middle Miocene hominoid from northern Kenya, are reported. The caudal thoracic vertebral body of N. kerioi has a rounded median ventral keel and its lateral sides are moderately concave. The lumbar vertebral body has an obvious median ventral keel. Based on a comparison of vertebral body cranial articular surface size between the caudal thoracic vertebrae in the present study and one discussed in a previous study (KNM-BG 35250BO, a diaphragmatic vertebra), N. kerioi has at least two post-diaphragmatic vertebrae (rib-bearing lumbar-type thoracic vertebrae), unlike extant hominoids. It also has thick, rounded, and moderately long metapophyses on the lumbar vertebra that project dorsolaterally. The spinous process bases of its caudal thoracic and lumbar vertebrae originate caudally between the postzygapophyses, as described previously in the KNM-BG 35250 holotype specimen. In other words, the postzygapophyses of N. kerioi do not project below the caudal border of the spinous processes, similar to those of extant great apes, and unlike small apes and monkeys, which have more caudally projecting postzygapophyses. Nacholapithecus kerioi has a craniocaudally expanded spinous process in relation to vertebral body length, also similar to extant great apes. Both these spinous process features of N. kerioi differ from those of Proconsul nyanzae. The caudal thoracic vertebra of N. kerioi has a caudally directed spinous process, whose tip is tear-drop shaped. These features resemble those of extant apes. The morphology of the spinous process tips presumably helps vertebral stability by closely stacking adjacent spinous process tips as seen in extant hominoids. The morphology of the spinous process and postzygapophyses limits the intervertebral space and contributes to the stability of the functional lumbar region as seen in extant great apes, suggesting that antipronograde activity was included in the positional behavior of N. kerioi. PMID- 26553817 TI - Spinal cord evolution in early Homo. AB - The discovery at Nariokotome of the Homo erectus skeleton KNM-WT 15000, with a narrow spinal canal, seemed to show that this relatively large-brained hominin retained the primitive spinal cord size of African apes and that brain size expansion preceded postcranial neurological evolution. Here we compare the size and shape of the KNM-WT 15000 spinal canal with modern and fossil taxa including H. erectus from Dmanisi, Homo antecessor, the European middle Pleistocene hominins from Sima de los Huesos, and Pan troglodytes. In terms of shape and absolute and relative size of the spinal canal, we find all of the Dmanisi and most of the vertebrae of KNM-WT 15000 are within the human range of variation except for the C7, T2, and T3 of KNM-WT 15000, which are constricted, suggesting spinal stenosis. While additional fossils might definitively indicate whether H. erectus had evolved a human-like enlarged spinal canal, the evidence from the Dmanisi spinal canal and the unaffected levels of KNM-WT 15000 show that unlike Australopithecus, H. erectus had a spinal canal size and shape equivalent to that of modern humans. Subadult status is unlikely to affect our results, as spinal canal growth is complete in both individuals. We contest the notion that vertebrae yield information about respiratory control or language evolution, but suggest that, like H. antecessor and European middle Pleistocene hominins from Sima de los Huesos, early Homo possessed a postcranial neurological endowment roughly commensurate to modern humans, with implications for neurological, structural, and vascular improvements over Pan and Australopithecus. PMID- 26553818 TI - A geometric morphometric study of a Middle Pleistocene cranium from Hexian, China. AB - The Hexian calvarium is one of the most complete and well-preserved Homo erectus fossils ever found in east Asia, apart from the Zhoukoudian specimens. Various methods bracket the age of the Hexian fossil to between 150 and 412 ka (thousands of years ago). The Hexian calvarium has been considered to be H. erectus given its morphological similarities to Zhoukoudian and Javan H. erectus. However, discussion continues regarding the affinities of the Hexian specimen with other H. erectus fossils. The arguments mainly focus on its relationships to other Asian H. erectus fossils, including those from both China and Java. To better determine the affinities of the Hexian cranium, our study used 3D landmark and semilandmark geometric morphometric techniques and multivariate statistical analyses to quantify the shape of the neurocranium and to compare the Hexian cranium to other H. erectus specimens. The results of this study confirmed the morphological similarities between Hexian and Chinese H. erectus in overall morphology, and particularly in the structure of the frontal bone and the posterior part of the neurocranium. Although the Hexian specimen shows the strongest connection to Chinese H. erectus, the morphology of the lateral neurocranium resembles early Indonesian H. erectus specimens, possibly suggesting shared common ancestry or gene flow from early Indonesian populations. Overall cranial and frontal bone morphology are strongly influenced by geography. Although geographically intermediate between Zhoukoudian and Indonesian H. erectus, the Hexian specimen does not form part of an obvious morphological gradient with regard to overall cranial shape. PMID- 26553819 TI - The effectiveness of using carbonate isotope measurements of body tissues to infer diet in human evolution: Evidence from wild western chimpanzees (Pan troglodytes verus). AB - Changes in diet throughout hominin evolution have been linked with important evolutionary changes. Stable carbon isotope analysis of inorganic apatite carbonate is the main isotopic method used to reconstruct fossil hominin diets; to test its effectiveness as a paleodietary indicator we present bone and enamel carbonate carbon isotope data from a well-studied population of modern wild western chimpanzees (Pan troglodytes verus) of known sex and age from Tai, Cote d'Ivoire. We found a significant effect of age class on bone carbonate values, with adult chimpanzees being more (13)C- and (18)O-depleted compared to juveniles. Further, to investigate habitat effects, we compared our data to existing apatite data on eastern chimpanzees (P. troglodytes schweinfurthii) and found that the Tai chimpanzees are significantly more depleted in enamel delta(13)Cap and delta(18)Oap compared to their eastern counterparts. Our data are the first to present a range of tissue-specific isotope data from the same group of wild western chimpanzees and, as such, add new data to the growing number of modern non-human primate comparative isotope datasets providing valuable information for the interpretation of diet throughout hominin evolution. By comparing our data to published isotope data on fossil hominins we found that our modern chimpanzee bone and enamel data support hypotheses that the trend towards increased consumption of C4 foods after 4 Ma (millions of years ago) is unique to hominins. PMID- 26553820 TI - Distinct functional roles of primate grasping hands and feet during arboreal quadrupedal locomotion. AB - It has long been thought that quadrupedal primates successfully occupy arboreal environments, in part, by relying on their grasping feet to control balance and propulsion, which frees their hands to test unstable branches and forage. If this interlimb decoupling of function is real, there should be discernible differences in forelimb versus hind limb musculoskeletal control, specifically in how manual and pedal digital flexor muscles are recruited to grasp during arboreal locomotion. New electromyography data from extrinsic flexor muscles in red ruffed lemurs (Varecia rubra) walking on a simulated arboreal substrate reveal that toe flexors are activated at relatively higher levels and for longer durations than finger flexors during stance phase. This demonstrates that the extremities of primates indeed have different functional roles during arboreal locomotion, with the feet emphasizing maintenance of secure grips. When this dichotomous muscle activity pattern between the forelimbs and hind limbs is coupled with other features of primate quadrupedal locomotion, including greater hind limb weight support and the use of diagonal-sequence footfall patterns, a complex suite of biomechanical characters emerges in primates that allow for the co-option of hands toward non-locomotor roles. Early selection for limb functional differentiation in primates probably aided the evolution of fine manipulation capabilities in the hands of bipedal humans. PMID- 26553821 TI - [Gaze-evoked nystagmus due to ischemic infarction involving the nucleus prepositus hypoglossi, a case report]. PMID- 26553822 TI - [Atypical onset corticobasal degeneration]. PMID- 26553824 TI - Improving surgical systems in low- and middle-income countries: an inclusive framework for monitoring and evaluation. AB - High disease burden and inadequate resources have formed the basis for advocacy to improve surgical care in low- and middle-income countries (LMICs). Current measures are heavily focused on availability of resources rather than impact and fail to fully describe how surgery can be more integrated into health systems. We propose a new monitoring and evaluation framework of surgical care in LMICs to integrate surgical diseases into broader health system considerations and track efforts toward improved population health. Although more discussion is required, we seek to broaden the dialogue of how to improve surgical care in LMICs through this comprehensive framework. PMID- 26553823 TI - Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease. AB - We have previously reported in Alzheimer's disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD. PMID- 26553825 TI - Diagnostics in a digital age: an opportunity to strengthen health systems and improve health outcomes. AB - Diagnostics play a critical role in clinical decision making, and in disease control and prevention. Rapid point-of-care (POC) tests for infectious diseases can improve access to diagnosis and patient management, but the quality of these tests vary, quality of testing is often not assured and there are few mechanisms to capture test results for surveillance when the testing is so decentralised. A new generation of POC molecular tests that are highly sensitive and specific, robust and easy to use are now available for deployment in low resource settings. Decentralisation of testing outside of the laboratory can put tremendous stress on the healthcare system and presents challenges for training and quality assurance. A feature of many of these POC molecular devices is that they are equipped with data transmission capacities. In a digital age, it is possible to link data from diagnostic laboratories and POC test readers and devices to provide data on testing coverage, disease trends and timely information for early warning of infectious disease outbreaks to inform design or optimisation of disease control and elimination programmes. Data connectivity also allows control programmes to monitor the quality of tests and testing, and optimise supply chain management; thus, increasing the efficiency of healthcare systems and improving patient outcomes. PMID- 26553826 TI - Is cost-related non-collection of prescriptions associated with a reduction in health? Findings from a large-scale longitudinal study of New Zealand adults. AB - OBJECTIVE: To investigate whether cost-related non-collection of prescription medication is associated with a decline in health. SETTINGS: New Zealand Survey of Family, Income and Employment (SoFIE)-Health. PARTICIPANTS: Data from 17 363 participants with at least two observations in three waves (2004-2005, 2006-2007, 2008-2009) of a panel study were analysed using fixed effects regression modelling. PRIMARY OUTCOME MEASURES: Self-rated health (SRH), physical health (PCS) and mental health scores (MCS) were the health measures used in this study. RESULTS: After adjusting for time-varying confounders, non-collection of prescription items was associated with a 0.11 (95% CI 0.07 to 0.15) unit worsening in SRH, a 1.00 (95% CI 0.61 to 1.40) unit decline in PCS and a 1.69 (95% CI 1.19 to 2.18) unit decline in MCS. The interaction of the main exposure with gender was significant for SRH and MCS. Non-collection of prescription items was associated with a decline in SRH of 0.18 (95% CI 0.11 to 0.25) units for males and 0.08 (95% CI 0.03 to 0.13) units for females, and a decrease in MCS of 2.55 (95% CI 1.67 to 3.42) and 1.29 (95% CI 0.70 to 1.89) units for males and females, respectively. The interaction of the main exposure with age was significant for SRH. For respondents aged 15-24 and 25-64 years, non-collection of prescription items was associated with a decline in SRH of 0.12 (95% CI 0.03 to 0.21) and 0.12 (95% CI 0.07 to 0.17) units, respectively, but for respondents aged 65 years and over, non-collection of prescription items had no significant effect on SRH. CONCLUSION: Our results show that those who do not collect prescription medications because of cost have an increased risk of a subsequent decline in health. PMID- 26553827 TI - How socioeconomic inequalities impact pathways of care for coronary artery disease among elderly patients: study protocol for a qualitative longitudinal study. AB - INTRODUCTION: Several studies have identified that socioeconomic inequalities in coronary artery disease (CAD) morbidity and mortality lead to a disadvantage in patients with low socioeconomic status (SES). International studies have shown that socioeconomic inequalities also exist in terms of access, utilisation and quality of cardiac care. The aim of this qualitative study is to provide information on the impact of socioeconomic inequalities on the pathway of care for CAD, and to establish which factors lead to socioeconomic inequality of care to form and expand existing scientific theories. METHODS AND ANALYSIS: A longitudinal qualitative study with 48 patients with CAD, aged 60-80 years, is being conducted. Patients have been recruited consecutively at the University Hospital in Halle/Saale, Germany, and will be followed for a period of 6 months. Patients are interviewed two times face-to-face using semistructured interviews. Data are transcribed and analysed based on grounded theory. ETHICS AND DISSEMINATION: Only participants who have been informed and who have signed a declaration of consent have been included in the study. The study complies rigorously with data protection legislation. Approval of the Ethical Review Committee at the Martin-Luther University Halle-Wittenberg, Germany was obtained. The results of the study will be presented at several congresses, and will be published in high-quality peer-reviewed international journals. TRIAL REGISTRATION NUMBER: This study has been registered with the German Clinical Trials Register and assigned DRKS00007839. PMID- 26553828 TI - Clustering of pain and its associations with health in people aged 50 years and older: cross-sectional results from the North Staffordshire Osteoarthritis Project. AB - OBJECTIVE: Most pain in patients aged >=50 years affects multiple sites and yet the predominant mode of presentation is single-site syndromes. The aim of this study was to investigate if pain sites form clusters in this population and if any such clusters are associated with health factors other than pain. SETTING: Six general practices in North Staffordshire, UK. DESIGN: Cross-sectional, postal questionnaire, study. PARTICIPANTS: Community-dwelling adults aged >=50 years registered at the general practices. MAIN OUTCOMES MEASURES: Number of pain sites was measured by asking participants to shade sites of pain lasting >=1 day in the past 4 weeks on a blank body manikin. Health factors measured included anxiety and depression (Hospital and Anxiety Depression Scale), cognitive complaint (Sickness Impact Profile) and sleep. Pain site clustering was investigated using latent class analysis. Association of clusters with health factors, adjusted for age, sex, body mass index and morbidities, was analysed using multinomial regression models. RESULTS: 13 986 participants (adjusted response 70.6%) completed a questionnaire, of whom 12 408 provided complete pain data. Four clusters of participants were identified: (1) low number of pain sites (36.6%), (2) medium number of sites with no back pain (31.5%), (3) medium number of sites with back pain (17.9%) and (4) high number of sites (14.1%). Compared to Cluster 1, other clusters were associated with poor health. The strongest associations (relative risk ratios, 95% CI) were with Cluster 4: depression (per unit change in score) 1.11 (1.08 to 1.14); cognitive complaint 2.60 (2.09 to 3.24); non restorative sleep 4.60 (3.50 to 6.05). CONCLUSIONS: These results indicate that in a general population aged >=50 years, pain forms four clusters shaped by two dimensions-number of pain sites (low, medium, high) and, within the medium cluster, the absence or presence of back pain. The usefulness of primary care treatment approaches based on this simple classification should be investigated. PMID- 26553829 TI - Community preparedness for emergency: a cross-sectional survey of residents in Heilongjiang of China. AB - OBJECTIVE: This article aims to identify factors that shape the knowledge, attitudes and behaviours of community residents in China's Heilongjiang province towards emergency preparedness. Findings of such a study may provide evidence to support the development of effective public risk communication strategies and education campaigns. DESIGN: A cross-sectional household questionnaire survey was conducted in Heilongjiang province in 2014. A stratified cluster sampling strategy was employed to select study participants. The questionnaires were administered using face-to-face interviews. 2800 questionnaires were completed, among which 2686 (95.9%) were considered valid for data analyses. A multivariate logistic regression model was adopted to identify the extent to which the independent variables were associated with emergency preparedness. RESULTS: Fewer than 5% respondents were well prepared for emergency. Over half (52%) of poorly prepared respondents did not know what to do in emergency; women (OR=1.691), higher household income (OR ranging from 1.666 to 2.117), previous experience with emergency (OR=1.552), higher levels of knowledge about emergency (OR=2.192), risk awareness (OR=1.531), self-efficacy (OR=1.796), as well as positive attitudes towards emergency preparedness (OR=2.265) were significant predictors for emergency preparedness. Neither educational attainment nor exposure to awareness-raising entered into the logic regression model as a significant predictor for emergency preparedness. CONCLUSIONS: The level of emergency preparedness in Heilongjiang residents is very low, which is linked with poor knowledge and attitudes of the residents towards emergency preparedness. Future emergency awareness campaigns should be more focused and tailored to the needs of intended audience, taking into consideration of their usual source of information and knowledge in relation to emergency. PMID- 26553831 TI - Funding allocation to surgery in low and middle-income countries: a retrospective analysis of contributions from the USA. AB - OBJECTIVE: The funds available for global surgical delivery, capacity building and research are unknown and presumed to be low. Meanwhile, conditions amenable to surgery are estimated to account for nearly 30% of the global burden of disease. We describe funds given to these efforts from the USA, the world's largest donor nation. DESIGN: Retrospective database review. US Agency for International Development (USAID), National Institute of Health (NIH), Foundation Center and registered US charitable organisations were searched for financial data on any organisation giving exclusively to surgical care in low and middle income countries (LMICs). For USAID, NIH and Foundation Center all available data for all years were included. The five recent years of financial data per charitable organisation were included. All nominal dollars were adjusted for inflation by converting to 2014 US dollars. SETTING: USA. PARTICIPANTS: USAID, NIH, Foundation Center, Charitable Organisations. PRIMARY AND SECONDARY OUTCOME MEASURES: Cumulative funds appropriated to global surgery. RESULTS: 22 NIH funded projects (totalling $31.3 million) were identified, primarily related to injury and trauma. Six relevant USAID projects were identified-all obstetric fistula care totalling $438 million. A total of $105 million was given to universities and charitable organisations by US foundations for 12 different surgical specialties. 95 US charitable organisations representing 14 specialties totalled revenue of $2.67 billion and expenditure of $2.5 billion. CONCLUSIONS AND RELEVANCE: Current funding flows to surgical care in LMICs are poorly understood. US funding predominantly comes from private charitable organisations, is often narrowly focused and does not always reflect local needs or support capacity building. Improving surgical care, and embedding it within national health systems in LMICs, will likely require greater financial investment. Tracking funds targeting surgery helps to quantify and clarify current investments and funding gaps, ensures resources materialise from promises and promotes transparency within global health financing. PMID- 26553830 TI - Feedback on SMS reminders to encourage adherence among patients taking antipsychotic medication: a cross-sectional survey nested within a randomised trial. AB - OBJECTIVES: To explore feedback on tailored SMS reminders to encourage medication adherence and outpatient treatment among patients taking antipsychotic medication, and associations related to the feedback. DESIGN: A cross-sectional survey nested within a nationwide randomised clinical trial ("Mobile.Net" ISRCTN27704027). SETTING: Psychiatric outpatient care in Finland. PARTICIPANTS: Between September 2012 and December 2013, 403 of 558 adults with antipsychotic medication responded after 12 months of SMS intervention. MAIN OUTCOME MEASURE: Feedback was gathered with a structured questionnaire based on Technology Acceptance Model theory. Data were analysed by Pearson's chi(2) test, binary logistic regression and stepwise multiple regression analyses. RESULTS: Almost all participants (98%) found the SMS reminders easy to use and 87% felt that the SMS did not cause harm. About three-quarters (72%) were satisfied with the SMS received, and 61% found it useful. Divorced people were particularly prone to find SMS reminders useful (chi(2)=13.17, df=6, p=0.04), and people seeking employment were more often 'fully satisfied' with the SMS compared with other groups (chi(2)=10.82, df=4, p=0.029). People who were older at first contact with psychiatric services were more often 'fully satisfied' than younger groups (OR=1.02, 95% CI 1.01 to 1.04, p=0.007). CONCLUSIONS: The feedback of patients taking antipsychotic medication on SMS services was generally positive. Overall, people were quite satisfied despite considerable variation in their sociodemographic background and illness history. Our results endorse that the use of simple easy-to-use existing technology, such as mobile phones and SMS, is acceptable in psychiatric outpatient services. Moreover, people using psychiatric outpatient services are able to use this technology. This acceptable and accessible technology can be easily tailored to each patient's needs and could be customised to the needs of the isolated or jobless. This is an area in which much careful evaluation is needed. PMID- 26553832 TI - A nationwide study of patients hospitalised for poisoning in Korea based on Korea National Hospital Discharge In-Depth Injury Survey data from 2005 to 2009. AB - OBJECTIVES: In light of the need to develop an integrated database on poisoning incidents in Korea, this study seeks to determine the characteristics of poisoning incidents in Korea by age, gender, location of incident, causative substance and patient prognosis. DATA SOURCES: The Korea National Hospital Discharge In-Depth Injury Survey results (2005-2009) from the Korea Centers for Disease Control and Prevention were used. PARTICIPANTS: 3826 participants in the survey who had been hospitalised for poisoning incidents. RESULTS: The poisoning hospitalisation rate per 100,000 population was higher in women (1.735) than in men (1.372) and increased with age: the rate was 0.458 among individuals aged <=9 years, 0.481 among those aged 10-19 years, 1.584 among those aged 20-64 years and 4.053 among those aged >=65 years. The intentional poisoning hospitalisation rate differed by gender and age group. Women aged <=19 years and 20-64 years showed a higher hospitalisation rate than men, while men aged >=65 years showed a higher hospitalisation rate than women in the same age group. The most common poisoning substance was pesticides (33.6%), while antiepileptic, sedative-hypnotic and antiparkinsonism drugs and psychotropic drugs, not elsewhere classified were also very common. Poisoning in those aged <=9 years usually involved other drugs, while pesticides were the most common substances in those aged 20-64 years and >=65 years. CONCLUSIONS: This study analysed poisoning incidents in Korea from 2005 to 2009, by age and gender, causative substance, and characteristics. The results of this study may serve as evidence for new strategies in Korea to prevent poisoning. PMID- 26553834 TI - Protocol for the design of an instrument to measure preadolescent children's self report of covert aggression and bullying. AB - INTRODUCTION: Covert bullying in schools is associated with a range of academic, social, emotional and physical health problems. Much research has focused on bullying, but there remains a gap in understanding about covert aggression and how to most accurately and reliably measure children's own reports of this behaviour. This paper reviews relevant literature and outlines a research project that aims to develop a self-report instrument that effectively measures covert aggression and bullying. It is anticipated that this research will result in a standardised instrument that is suitable for exploring preadolescent children's experiences of covert aggressive behaviour. The data collected by the instrument will enhance health and education professionals understanding of covert bullying behaviours and will inform the design and evaluation of interventions. METHODS AND ANALYSIS: Relational developmental systems theory will guide the design of an online self-report instrument. The first phase of the project will include a critical review of the research literature, focus groups with children aged 8-12 years (grades 4-6) in Perth, Western Australia, and expert review. The instrument will be explored for content and face validity prior to the assessment of convergent and discriminant validity, internal consistency and test-retest reliability. ETHICS AND DISSEMINATION: The study has been approved by the Curtin University of Human Research Ethics Committee (RDHS-38-15) and by the Executive Principal of the participating school. PMID- 26553833 TI - A cross-sectional study of bacterial vaginosis, intravaginal practices and HIV genital shedding; implications for HIV transmission and women's health. AB - OBJECTIVES: Bacterial vaginosis (BV) is associated with an increased risk of HIV transmission, and intravaginal practices (IVP) are an important risk factor for developing BV. The relationship between IVP, BV and HIV lower genital shedding, responsible for HIV transmission, has not been examined in women receiving antiretrovirals in Zambia. DESIGN: Cross-sectional study. SETTING: Community Health Center in Lusaka, Zambia. PARTICIPANTS AND METHODS: Participants were HIV infected women receiving antiretroviral therapy and engaging in IVP (n=128). Participants completed audio computer-administered self-interviews to assess IVP and underwent a vaginal examination. BV was diagnosed using Nugent criteria. HIV 1 lower genital shedding was assessed by measuring HIV-1 RNA in cervicovaginal lavages. RESULTS: Most women engaged in IVP daily (114, 89.0%) and 81 (63.3%) of the participants had BV. HIV-1 genital shedding was detected in 18 (14.2%) participants. BV was associated with daily use of IVP (prevalence ratio, PR=4.58, CI 1.26 to 16.64, p=0.02) and weekly use of traditional medicines for IVP (PR=1.33, CI 1.05 to 1.68, p=0.02). The only factor associated with HIV-1 lower genital shedding was plasma viraemia (PR=4.61, CI 2.02 to 10.54, p<0.001). Neither IVP nor BV were associated with HIV shedding. CONCLUSIONS: Despite the frequency of IVP and high prevalence of BV, plasma viraemia was the primary factor associated with HIV lower genital shedding. These findings support early initiation of antiretrovirals as an HIV prevention tool. Given adverse health outcomes associated with BV, the association between frequent IVP and BV, and the powerful local norms and traditions encouraging IVP, there is a need for studies assessing culturally tailored interventions to decrease BV in high-prevalence settings. PMID- 26553835 TI - Comparison of transient associations of air pollution and AMI hospitalisation in two cities of Alberta, Canada, using a case-crossover design. AB - OBJECTIVE: To investigate reproducibility of outcomes for short-term associations between ambient air pollutants and acute myocardial infarction (AMI) hospitalisation in 2 urban populations. DESIGN: Using a time-stratified design, we conducted independent case-crossover studies of AMI hospitalisation events over the period 1999-2010 in the geographically close and demographically similar cities of Calgary and Edmonton, Alberta, Canada. Patients with his/her first AMI hospitalisation event were linked with air pollution data from the National Ambient Pollution Surveillance database and meteorological data from the National Climatic Data Center database. Patients were further divided into subgroups to examine adjusted pollution effects. Effects of pollution levels with 0-3-day lag were modelled using conditional logistic regression and adjusted for daily average ambient temperature, dew point temperature and wind speed. SETTING: Population-based studies in Calgary/Edmonton. PARTICIPANTS: 12,066/10,562 first time AMI hospitalisations in Calgary/Edmonton. MAIN OUTCOME MEASURES: Association (adjusted OR) between daily ambient air pollution levels and hospitalisation for AMI. RESULTS: Among 600 potential air pollution effect variables investigated for the Calgary (Edmonton) population, only 1.17% (0.67%) was statistically significant by using the traditional 5% criterion. None of the effect variables were reproduced in the 2 cities, despite their geographic closeness (within 300 km of each other), and demographic and air pollution similarities. CONCLUSIONS: Comparison of independent investigations of the effect of air pollution on risk of AMI hospitalisation in Calgary and Edmonton, Alberta, indicated that none of the air pollutants investigated-CO, NO, NO2, O3 and particulate matter (PM2.5) showed consistent positive associations with increased risk of AMI hospitalisation. PMID- 26553836 TI - Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial. AB - INTRODUCTION: Neurodegeneration is a widely accepted contributor to the development of long-term disability in multiple sclerosis (MS). While current therapies in MS predominantly target inflammation and reduce relapse rate they have been less effective at preventing long-term disability. The identification and evaluation of effective neuroprotective therapies within a trial paradigm are key unmet needs. Emerging evidence supports amiloride, a licenced diuretic, as a neuroprotective agent in MS through acid sensing ion channel blockade. Optic neuritis (ON) is a common manifestation of MS with correlates of inflammation and neurodegeneration measurable within the visual pathways. Amiloride Clinical Trial In Optic Neuritis (ACTION) will utilise a multimodal approach to assess the neuroprotective efficacy of amiloride in acute ON. METHODS AND ANALYSIS: 46 patients will be recruited within 28 days from onset of ON visual symptoms and randomised on a 1:1 basis to placebo or amiloride 10 mg daily. Double-blinded treatment groups will be balanced for age, sex and visual loss severity by a random-deterministic minimisation algorithm. The primary objective is to demonstrate that amiloride is neuroprotective in ON as assessed by scanning laser polarimetry of the peripapillary retinal nerve fibre layer (RNFL) thickness at 6 months in the affected eye compared to the unaffected eye at baseline. RNFL in combination with further retinal measures will also be assessed by optical coherence tomography. Secondary outcome measures on brain MRI will include cortical volume, diffusion-weighted imaging, resting state functional MRI, MR spectroscopy and magnetisation transfer ratio. In addition, high and low contrast visual acuity, visual fields, colour vision and electrophysiology will be assessed alongside quality of life measures. ETHICS AND DISSEMINATION: Ethical approval was given by the south central Oxford B research ethics committee (REC reference: 13/SC/0022). The findings from ACTION will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION NUMBER: EudraCT2012-004980-39, ClinicalTrials.gov Identifier: NCT01802489. PMID- 26553837 TI - Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study. AB - INTRODUCTION: Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the woman's constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman's health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study. METHODS: The prospective cohort feasibility study will recruit nulliparous women aged 18-40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments. ETHICS AND DISSEMINATION: The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events. TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT02419898. PMID- 26553838 TI - 'Big needles, small bodies'-the absence of acupuncture treatment for infants in contemporary Shanghai: a qualitative study. AB - OBJECTIVE: To explore contemporary practices and clinical recommendations regarding the use of acupuncture for infants by Traditional Chinese Medicine (TCM) practitioners in Shanghai. DESIGN: A qualitative study consisting of four field visits between February 2014 and March 2015. Data was collected using participant observation, focus group interview, in-depth interview, textbook page analysis and informant validation. PARTICIPANTS: 14 Shanghainese professionals, including interpreters and TCM practitioners, of which seven were acupuncturists. SETTING: The Longhua Hospital (paediatric, acupuncture and Tui na departments) in southern Shanghai and the campus of the Shanghai University of Traditional Chinese Medicine. RESULTS: The Longhua Hospital outpatient acupuncture clinic receives 400 consultations on average per day. Children, including patients from the paediatric department, are referred to this clinic. During 3 days of participant observations at this department, we saw two children. No infants. During 3 days at the paediatric department and 1 day at the Tui na department we saw no referrals. Formal interviews and informal conversations with acupuncturists and other TCM professionals revealed that acupuncture was neither routinely practiced nor recommended for infants and small children. Acupuncture was considered potentially painful for this young patient population. Alternative treatment options such as herbal treatments or medical massage were widely available and preferred. Western medical diagnostics and treatment were also used, recommended, and trusted. CONCLUSIONS: Acupuncture for infants is not a preferred therapeutic method among TCM practitioners working in contemporary Shanghai. Acupuncture on broad indications in infants appears to be a Western practice with little basis in TCM modern-day practice. PMID- 26553839 TI - Validity assessment of self-reported medication use by comparing to pharmacy insurance claims. AB - OBJECTIVES: In Japan, an annual health check-up and health promotion guidance programme was established in 2008 in accordance with the Act on Assurance of Medical Care for the Elderly. A self-reported questionnaire on medication use is a required item in this programme and has been used widely, but its validity has not been assessed. The aim of this study was to evaluate the validity of this questionnaire by comparing self-reported usage to pharmacy insurance claims. SETTING: This is a population-based validation study. Self-reported medication use for hypertension, diabetes and dyslipidaemia is the evaluated measurement. Data on pharmacy insurance claims are used as a reference standard. PARTICIPANTS: Participants were 54,712 beneficiaries of the National Health Insurance of Chiba City. PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity, specificity and kappa statistics of the self-reported medication-use questionnaire for predicting actual prescriptions during 1 month (that of the check-up) and 3 months (that of the check-up and the previous 2 months) were calculated. RESULTS: Sensitivity and specificity scores of questionnaire data for predicting insurance claims covering 3 months were, respectively, 92.4% (95% CI 91.9 to 92.8) and 86.4% (95% CI 86.0 to 86.7) for hypertension, 82.6% (95% CI 81.1 to 84.0) and 98.5% (95% CI 98.4 to 98.6) for diabetes, and 86.2% (95% CI 85.5 to 86.8) and 91.0% (95% CI 90.8 to 91.3) for dyslipidaemia. Corresponding kappa statistics were 70.9% (95% CI 70.1 to 71.7), 77.1% (95% CI 76.2 to 77.9) and 69.8% (95% CI 68.9 to 70.6). The specificity was significantly higher for questionnaire data covering 3 months compared with data covering 1 month for all 3 conditions. CONCLUSIONS: Self reported questionnaire data on medication use had sufficiently high validity for further analyses. Item responses showed close agreement with actual prescriptions, particularly those covering 3 months. PMID- 26553840 TI - A qualitative analysis of New Zealand retailers' responses to standardised packaging legislation and tobacco industry opposition. AB - OBJECTIVES: Many of the approximately 8000 New Zealand retailers selling tobacco are small stores that tobacco companies have represented as victims of policy measures designed to reduce smoking. Despite this depiction, many retailers experience considerable ambivalence in selling tobacco, a product they know harms their customers. We explored how retailers perceived the proposed introduction of standardised (or 'plain') packaging and their assessment of arguments made by tobacco companies in submissions on proposed standardised packaging legislation. PARTICIPANTS: Using qualitative in-depth interviews, we recruited and interviewed 23 retailers of dairies (small convenience stores), small supermarkets, and service stations. ANALYSES: Data were analysed using a protocol-driven approach; this stance enabled direct analysis of tobacco companies' arguments, particularly those purporting to represent retailers' concerns. RESULTS: Retailers were concerned about the financial implications of standardised packaging and the effects it may have on their ability to provide rapid and efficient customer service. However, few thought standardised packaging would foster illicit trade or spawn further regulation; most placed public health goals ahead of tobacco companies' 'rights', and many supported government intervention to protect population health. CONCLUSIONS: Retailers held ambivalent views on standardised packaging; while they were concerned about short-term effects on their business, they recognised the harm smoking causes. Policymakers and health researchers could collaborate more effectively with retailers by assisting them to create financially viable roles more compatible with public health objectives. PMID- 26553842 TI - Commentary: Please sir, I want some more (and something else). PMID- 26553841 TI - Association between secure patient-clinician email and clinical services utilisation in a US integrated health system: a retrospective cohort study. AB - OBJECTIVE: To assess associations between secure patient-clinician email use and clinical services utilisation over time. DESIGN: Retrospective cohort study between July 2010 and December 2013. Controlling for a utilisation surge around first secure email use, we analysed difference of differences between propensity score-matched groups of secure patient-clinician email users and non-users for utilisation 1-12 months before and 7-18 months after first email (users) or a randomly assigned index date (non-users). SETTING: US integrated healthcare delivery system. PARTICIPANTS: 9345 adults with first secure email use between July 2011 and July 2012 and continuous enrolment for >=30 months and 9345 adults without secure email use between July 2010 and July 2012 matched to users on demographics, health status, and baseline utilisation. PRIMARY OUTCOME MEASURES: Rates of office visits, patient-initiated phone calls, scheduled telephone visits, after-hours clinic visits, emergency department visits, and hospitalisations. RESULTS: After controlling for multiple factors, no statistically significant differences in utilisation between secure email users and non-users occurred. Utilisation transiently increased by 88-237% around first email use. Annual rates of patient-initiated phone calls decreased among secure email users, 0.2 fewer calls per person (95% CI -0.3 to -0.1), from a mean of 4.1 calls per person 1-12 months before first use to a mean of 3.8 calls per person 7 18 months after first use. Rates of patient-initiated phone calls also decreased among non-users, 0.1 fewer calls per person (95% CI -0.2 to 0.0), from a mean of 4.2 calls per person 1-12 months before the index date to mean of 4.1 calls per person 7-18 months after the index date. CONCLUSIONS: Compared with non-users, patient use of secure email with clinicians was not associated with statistically significant differences in clinical services utilisation 7-18 months after first use. PMID- 26553843 TI - Twin vaginal delivery is associated with lower umbilical arterial blood pH of the second twin and less intrapartum blood loss. AB - OBJECTIVE: To clarify actual differences in the neonatal as well as maternal outcome between completed twin vaginal delivery and cesarean delivery. METHODS: We collected the data from women with a twin pregnancy who delivered two live fetuses between 1 January and 31 December 2014 at 20 teaching hospitals (1) (1) PARTICIPANTS: Adachi Hospital, Hyogo Prefectural Amagasaki General Medical Center, Japan Baptist Hospital, Kitano Hospital, Kobe City Medical Center General Hospital, Kosaka Women's Hospital, Kurashiki Central Hospital, Kyoto University Hospital, Mitsubishi Kyoto Hospital, Nagahama Red Cross Hospital, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka National Hospital, Osaka Red Cross Hospital, Otsu Municipal Hospital, Otsu Red Cross Hospital, Red Cross Wakayama Medical Center, Saiseikai Noe Hospital, Shizuoka General Hospital, Takamatsu Red Cross Hospital and Tenri Hospital. in Japan. Only the cases that were retrospectively regarded as eligible for planned vaginal delivery were analyzed according to the actual mode of delivery. RESULTS: Umbilical arterial blood pH (UmA-pH) of the second twin was slightly but significantly lower in the vaginal delivery group (7.26 +/- 0.009) than in a cesarean delivery group (7.30 +/- 0.006). Vaginal delivery was the only independent risk factor for second twin's UmA-pH <7.20. Intrapartum blood loss was significantly larger in the cesarean delivery group (1444 +/- 63 g) than in the vaginal delivery group (820 +/- 109 g). Cesarean delivery was an independent risk factor for intrapartum blood loss >=1500 g. CONCLUSION: Twin vaginal deliveries were associated with slightly but significantly lower UmA-pH of the second twin, whereas twin cesarean delivery was associated with significantly larger intrapartum blood loss. Not only the neonatal risk but also the maternal risk should be taken into account when an optimal delivery mode for the twin pregnancy is considered. PMID- 26553844 TI - The predictive value of lactate peak detected by the magnetic resonance spectroscopy in the brain of growth-restricted fetuses for adverse perinatal outcomes. AB - OBJECTIVE: To compare perinatal outcomes between patients with and without abnormal Doppler findings and lactate peak in the fetal brain detected by magnetic resonance spectroscopy ((1)HMRS) and to assess the feasibility of fetal brain lactate in the prediction of adverse obstetric outcomes in growth restricted fetuses. METHODS: Pregnancies with FGR fetuses underwent Doppler ultrasonography and 3 Tesla (1)HMRS for the presence of lactate peak prior to the delivery. Patients were assigned into the following groups; normal Doppler, no lactate peak (Group 1), normal Doppler, lactate peak (+) (Group II), abnormal Doppler, no lactate peak (Group III), abnormal Doppler, lactate peak (+) (Group IV). RESULTS: Five perinatal deaths, all in Group IV, were encountered (p < 0.001). Perinatal death rate was higher in patients with Doppler flow abnormality ((5/12 (41.7%)) than in patients without Doppler abnormality (0/23) (p < 0.001) and was significantly higher in the presence (5/18 (27.8%)) than in the absence of lactate peak (0/17) (p = 0.019). CONCLUSIONS: Fetuses with brain lactate peak detected by (1)HMRS in addition to altered Doppler findings are more likely to develop short-term morbidities and perinatal death. Fetal brain lactate detected by (1)HMRS may represent a clinical marker of altered brain metabolism and further perinatal complications. PMID- 26553845 TI - In vitro and in vivo activity of a novel sorafenib derivative SC5005 against MRSA. AB - OBJECTIVES: The emergence of MRSA strains resistant to most antibiotics is a serious threat to public health. Based on our discovery that the tyrosine kinase inhibitor sorafenib exhibits inhibitory activity against Staphylococcus species, the objective of this study is to exploit this unique antibacterial activity of sorafenib to develop novel antibacterial agents against MRSA. METHODS: A sorafenib-based focused compound library was synthesized by substituting the pyridinyl and phenyl groups with different functional groups. The resulting sorafenib derivatives were screened for growth-suppressive activities against Staphylococcus aureus and Staphylococcus epidermidis following CLSI guidelines and for cytotoxicity towards human cells using MTT cell viability assays. Compounds with high selectivity for bacterial inhibition over cytotoxicity were further evaluated by time-kill assay and Caenorhabditis elegans and mice survival assays to evaluate their efficacy in vitro and in vivo. RESULTS: The screening of sorafenib derivatives led to the identification of compound SC5005 as a lead compound with high potency in killing different clinical strains of MRSA with an MIC90 of 0.5 mg/L and with low cytotoxicity, as demonstrated by IC50-to-MIC ratios of up to 40. In addition, SC5005 showed a significant protective effect in MSSA- or MRSA-infected C. elegans. Intraperitoneal administration of SC5005 at 10 mg/kg significantly improved the survival of MRSA-infected C57BL/6 mice. CONCLUSIONS: In light of its high potency in suppressing MRSA in both in vitro and in vivo models, SC5005 represents a potential lead agent for continued preclinical development as a therapeutic intervention against MRSA. PMID- 26553846 TI - Antifungal therapy: drug-drug interactions at your fingertips. AB - The Information Age has revolutionized the ability of healthcare professionals (HCPs) to oversee a substantial body of clinically relevant information literally at one's fingertips. In the field of clinical pharmacology, this may be particularly useful for managing drug-drug interactions (DDIs). A thorough understanding of the underlying mechanisms of DDIs allows the HCP to predict such interactions and avoid those of greatest clinical significance. Specifically, successful treatment with antifungal agents is complicated by the high potential to interact with other concomitant medications. We describe here the development of a real-time knowledge base of DDIs with antifungal agents, providing expert recommendations to HCPs on how to handle DDIs with these drugs. This new resource will facilitate rapid identification, quantification and classification of these DDIs by clinicians with varying levels of experience and resources worldwide, ultimately improving patient safety and strengthening health systems. PMID- 26553847 TI - Breakdown of low-level total petroleum hydrocarbons (TPH) in contaminated soil using grasses and willows. AB - A phytoremediation study targeting low-level total petroleum hydrocarbons (TPH) was conducted using cool- and warm-season grasses and willows (Salix species) grown in pots filled with contaminated sandy soil from the New Haven Rail Yard, CT. Efficiencies of the TPH degradation were assessed in a 90-day experiment using 20-8.7-16.6 N-P-K water-soluble fertilizer and fertilizer with molasses amendments to enhance phytoremediation. Plant biomass, TPH concentrations, and indigenous microbes quantified with colony-forming units (CFU), were assessed at the end of the study. Switchgrass grown with soil amendments produced the highest aboveground biomass. Bacterial CFU's were in orders of magnitude significantly higher in willows with soil amendments compared to vegetated treatments with no amendments. The greatest reduction in TPH occurred in all vegetated treatments with fertilizer (66-75%) and fertilizer/molasses (65-74%), followed sequentially by vegetated treatments without amendments, unvegetated treatments with amendments, and unvegetated treatments with no amendment. Phytoremediation of low level TPH contamination was most efficient where fertilization was in combination with plant species. The same level of remediation was achievable through the addition of grasses and/or willow combinations without amendment, or by fertilization of sandy soil. PMID- 26553848 TI - SepM, a Streptococcal Protease Involved in Quorum Sensing, Displays Strict Substrate Specificity. AB - Streptococcus mutans, a causative agent of dental caries, relies on multiple quorum-sensing (QS) pathways that coordinate the expression of factors needed for colonization in the oral cavity. S. mutans uses small peptides as QS signaling molecules that typically are secreted into the outside milieu. Competence stimulating peptide (CSP) is one such QS signaling molecule that functions through the ComDE two-component signal transduction pathway. CSP is secreted through NlmTE, a dedicated ABC transporter that cleaves off the N-terminal leader peptide to generate a mature peptide that is 21 residues long (CSP-21). We recently identified a surface-localized protease, SepM, which further cleaves the CSP-21 peptide at the C-terminal end and removes the last 3 residues to generate CSP-18. CSP-18 is the active QS molecule that interacts with the ComD sensor kinase to activate the QS pathway. In this study, we show that SepM specifically cleaves CSP-21 between the Ala18 and Leu19 residues. We also show that SepM recognizes only Ala at position 18 and Leu at position 19, although some CSP-18 variants with a substitution at position 18 can function equally as well as the QS peptide. Furthermore, we demonstrate that SepM homologs from other streptococci are capable of processing CSP-21 to generate functional CSP-18. IMPORTANCE: SepM is a membrane-associated streptococcal protease that processes competence-stimulating peptide (CSP) to generate an active quorum-sensing molecule in S. mutans. SepM belongs to the S16 family of serine proteases, and in this study, we found that SepM behaves as an endopeptidase. SepM displays strict substrate specificity and cleaves the peptide bond between the Ala and Leu residues. This is the first report of an endopeptidase that specifically cleaves these two residues. PMID- 26553849 TI - Transcriptome-Wide Identification of Hfq-Associated RNAs in Brucella suis by Deep Sequencing. AB - Recent breakthroughs in next-generation sequencing technologies have led to the identification of small noncoding RNAs (sRNAs) as a new important class of regulatory molecules. In prokaryotes, sRNAs are often bound to the chaperone protein Hfq, which allows them to interact with their partner mRNA(s). We screened the genome of the zoonotic and human pathogen Brucella suis 1330 for the presence of this class of RNAs. We designed a coimmunoprecipitation strategy that relies on the use of Hfq as a bait to enrich the sample with sRNAs and eventually their target mRNAs. By deep sequencing analysis of the Hfq-bound transcripts, we identified a number of mRNAs and 33 sRNA candidates associated with Hfq. The expression of 10 sRNAs in the early stationary growth phase was experimentally confirmed by Northern blotting and/or reverse transcriptase PCR. IMPORTANCE: Brucella organisms are facultative intracellular pathogens that use stealth strategies to avoid host defenses. Adaptation to the host environment requires tight control of gene expression. Recently, small noncoding RNAs (sRNAs) and the sRNA chaperone Hfq have been shown to play a role in the fine-tuning of gene expression. Here we have used RNA sequencing to identify RNAs associated with the B. suis Hfq protein. We have identified a novel list of 33 sRNAs and 62 Hfq associated mRNAs for future studies aiming to understand the intracellular lifestyle of this pathogen. PMID- 26553850 TI - Relative Rates of Amino Acid Import via the ABC Transporter GlnPQ Determine the Growth Performance of Lactococcus lactis. AB - The GlnPQ transporter from Lactococcus lactis has the remarkable feature of having two substrate-binding domains (SBDs) fused to the N terminus of the transmembrane domain (TMD), and thus four SBDs are present in the homodimeric complex. Although X-ray structures and ligand binding data are available for both SBDs, little is known of how different amino acids compete with each other for transport via GlnPQ. Here we show GlnPQ has a broader substrate specificity than previously thought, with the ability to take up asparagine, glutamine, and glutamic acid, albeit via different routes and with different affinities. Asparagine and glutamine compete with each other at the level of binding to SBD1 and SBD2 (with differences in dissociation constant), but at the same time SBD1 and SBD2 compete with each other at the level of interaction with the translocator domain (with differences in affinity constant and rate of transport). Although glutamine transport via SBD1 is outcompeted by physiological concentrations of asparagine, SBD2 ensures high rates of import of the essential amino acid glutamine. Taken together, this study demonstrates that even in the presence of competing asparagine concentrations, GlnPQ has a high capacity to transport glutamine, which matches the high needs of the cell for glutamine and glutamate. IMPORTANCE: GlnPQ is an ATP-binding cassette (ABC) transporter for glutamine, glutamic acid, and asparagine. The system is essential in various Gram positive bacteria, including L. lactis and several pathogens. Here we show how the amino acids compete with each other for binding to the multiple SBDs of GlnPQ and how these SBDs compete with each other for substrate delivery to the transporter. Overall, our results show that GlnPQ has evolved to transport diverse substrates via different paths and to optimally acquire the abundant and essential amino acid glutamine. PMID- 26553851 TI - Expression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli. AB - Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of diguanylate cyclases and phosphodiesterases. The phosphodiesterase PdeH was identified as a key regulator of motility in Escherichia coli, while deletions of any of the other 12 genes encoding potential phosphodiesterases did not interfere with motility. To analyze the roles of E. coli phosphodiesterases, we demonstrated that most of these proteins are expressed under laboratory conditions. We next isolated suppressor mutations in six phosphodiesterase genes, which reinstate motility in the absence of PdeH by reducing cellular levels of c-di-GMP. Expression of all mutant alleles also led to a reduction of biofilm formation. Thus, all of these proteins are bona fide phosphodiesterases that are capable of interfering with different c-di GMP-responsive output systems by affecting the global c-di-GMP pool. This argues that E. coli possesses several phosphodiesterases that are inactive under laboratory conditions because they lack appropriate input signals. Finally, one of these phosphodiesterases, PdeL, was studied in more detail. We demonstrated that this protein acts as a transcription factor to control its own expression. Motile suppressor alleles led to a strong increase of PdeL activity and elevated pdeL transcription, suggesting that enzymatic activity and transcriptional control are coupled. In agreement with this, we showed that overall cellular levels of c-di-GMP control pdeL transcription and that this control depends on PdeL itself. We thus propose that PdeL acts both as an enzyme and as a c-di-GMP sensor to couple transcriptional activity to the c-di-GMP status of the cell. IMPORTANCE: Most bacteria possess multiple diguanylate cyclases and phosphodiesterases. Genetic studies have proposed that these enzymes show signaling specificity by contributing to distinct cellular processes without much cross talk. Thus, spatial separation of individual c-di-GMP signaling units was postulated. However, since most cyclases and phosphodiesterases harbor N-terminal signal input domains, it is equally possible that most of these enzymes lack their activating signals under laboratory conditions, thereby simulating signaling specificity on a genetic level. We demonstrate that a subset of E. coli phosphodiesterases can be activated genetically to affect the global c-di-GMP pool and thus influence different c-di-GMP-dependent processes. Although this does not exclude spatial confinement of individual phosphodiesterases, this study emphasizes the importance of environmental signals for activation of phosphodiesterases. PMID- 26553852 TI - Dissecting the Structural Elements for the Activation of beta-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae. AB - beta-Ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either the active or inactive conformation. However, the structural elements which enable activation of FabG require further exploration. Here we report the findings of structural, enzymatic, and binding studies of the FabG protein found in the causative agent of cholera, Vibrio cholerae (vcFabG). vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between the dimeric and tetrameric states of vcFabG is related to changes in the conformations of the alpha4/alpha5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified to be the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loop beta4-alpha4 and loop beta5-alpha5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by binding and enzymatic assays for the corresponding mutants. IMPORTANCE: This paper describes the results of structural, enzymatic, and binding studies of FabG from Vibrio cholerae (vcFabG). In this work, we dissected the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacterial FabG, especially for the multidrug resistant strains of V. cholerae. PMID- 26553853 TI - GroEL2 of Mycobacterium tuberculosis Reveals the Importance of Structural Pliability in Chaperonin Function. AB - Intracellular protein folding is mediated by molecular chaperones, the best studied among which are the chaperonins GroEL and GroES. Conformational changes and allosteric transitions between different metastable states are hallmarks of the chaperonin mechanism. These conformational transitions between three structural domains of GroEL are anchored at two hinges. Although hinges are known to be critical for mediating the communication between different domains of GroEL, the relative importance of hinges on GroEL oligomeric assembly, ATPase activity, conformational changes, and functional activity is not fully characterized. We have exploited the inability of Mycobacterium tuberculosis GroEL2 to functionally complement an Escherichia coli groEL mutant to address the importance of hinge residues in the GroEL mechanism. Various chimeras of M. tuberculosis GroEL2 and E. coli GroEL allowed us to understand the role of hinges and dissect the consequences of oligomerization and substrate binding capability on conformational transitions. The present study explains the concomitant conformational changes observed with GroEL hinge variants and is best supported by the normal mode analysis. IMPORTANCE: Conformational changes and allosteric transitions are hallmarks of the chaperonin mechanism. We have exploited the inability of M. tuberculosis GroEL2 to functionally complement a strain of E. coli in which groEL expression is repressed to address the importance of hinges. The significance of conservation at the hinge regions stands out as a prominent feature of the GroEL mechanism in binding to GroES and substrate polypeptides. The hinge residues play a significant role in the chaperonin activity in vivo and in vitro. PMID- 26553854 TI - Idiopathic Partial Thrombosis (IPT) of the Corpus Cavernosum: A Hypothesis Generating Case Series and Review of the Literature. AB - INTRODUCTION: Idiopathic partial thrombosis (IPT) of the corpus cavernosum is a rare condition. The etiology is not fully understood; however, the presence of an either or not congenital web in these patients may contribute to the development of IPT. AIM: The aim of this study was to describe 18 new IPT cases and compare these with 38 cases found in the literature. METHODS: A multicenter retrospective analysis was performed. Descriptive statistics are given. MAIN OUTCOME MEASURES: The main outcome measures used were clinical presentation, clinical and radiographical diagnostics, treatment and resolution of symptoms. RESULTS: Patients most frequently presented with perineal swelling (10/18; 56%) and pain (13/18; 72%), unilateral (12/18; 67%) or bilateral (4/18; 22%), and pain during erection (10/18; 72%). Penile curvature, dysuria or fever (each 1/18; 6%) were uncommon presenting symptoms. In our series, magnetic resonance imaging demonstrated a fibrous web in the corpus cavernosum in 100% of cases and was more bilaterally (11/18; 61%) than unilaterally (7/18; 39%) diagnosed. Cycling was found to be a provocative factor for IPT occurrence in patients at risk as 61% (11/18) of patients reported being a frequent cyclist with the episode of IPT occurring immediately after or during cycling activity in 8 out of 18 patients (8/18; 44%). In five centers, 15 patients were treated conservatively, the majority being treated with therapeutic doses of low molecular weight heparin and simultaneous anti-aggregant therapy. In one center, all three patients were treated with a surgical approach. Complete resolution of symptoms was noted in only 50% of cases. CONCLUSION: IPT is a condition that presents typically with perineal pain and swelling. Cycling is often seen as a provocative factor, while the presence of a fibrous web at the level of the crurocavernosal junction is the underlying disorder allowing for entrapment of blood in the crura. Conservative treatment provides a reasonably good outcome in most cases. For therapy resistant cases, surgery can be considered. PMID- 26553855 TI - Reduce disease by improving environmental health. PMID- 26553856 TI - Confirming placement of nasogastric feeding tubes. PMID- 26553857 TI - Initial confusion after massive Allerject recall. PMID- 26553858 TI - The strange absence of things in the "culture" of the DSM-V. PMID- 26553859 TI - Patient safety still lags a decade after seminal study. PMID- 26553861 TI - Podcast: 10 questions with Canada's prison watchdog. PMID- 26553860 TI - Comparison of black-white disparities in preterm birth between Canada and the United States. AB - BACKGROUND: A higher risk of preterm birth among black women than among white women is well established in the United States. We compared differences in preterm birth between non-Hispanic black and white women in Canada and the US, hypothesizing that disparities would be less extreme in Canada given the different historical experiences of black populations and Canada's universal health care system. METHODS: Using data on singleton live births in Canada and the US for 2004-2006, we estimated crude and adjusted risk ratios and risk differences in preterm birth (< 37 wk) and very preterm birth (< 32 wk) among non Hispanic black versus non-Hispanic white women in each country. Adjusted models for the US were standardized to the covariate distribution of the Canadian cohort. RESULTS: In Canada, 8.9% and 5.9% of infants born to black and white mothers, respectively, were preterm; the corresponding figures in the US were 12.7% and 8.0%. Crude risk ratios for preterm birth among black women relative to white women were 1.49 (95% confidence interval [CI] 1.32 to 1.66) in Canada and 1.57 (95% CI 1.56 to 1.58) in the US (p value for heterogeneity [pH] = 0.3). The crude risk differences for preterm birth were 2.94 (95% CI 1.91 to 3.96) in Canada and 4.63 (95% CI 4.56 to 4.70) in the US (pH = 0.003). Adjusted risk ratios for preterm birth (pH = 0.1) were slightly higher in Canada than in the US, whereas adjusted risk differences were similar in both countries. Similar patterns were observed for racial disparities in very preterm birth. INTERPRETATION: Relative disparities in preterm birth and very preterm birth between non-Hispanic black and white women were similar in magnitude in Canada and the US. Absolute disparities were smaller in Canada, which reflects a lower overall risk of preterm birth in Canada than in the US in both black and white populations. PMID- 26553862 TI - Quebec considers extra billing. PMID- 26553863 TI - Share of health spending on doctors increases. PMID- 26553864 TI - Race and preterm birth rates in North America. PMID- 26553865 TI - Sildenafil Increases the p50 and Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right. AB - INTRODUCTION: Sildenafil (Viagra(r)) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. It is hypothesized that sildenafil will increase the release of oxygen from erythrocytes and shift the oxygen-hemoglobin curve to the right. AIM: The aim of this study was to investigate the effect of varying doses of sildenafil on the p50 of the oxygen hemoglobin dissociation curve in blood samples from eight (8) healthy adult male volunteers with normal hemoglobin HbAA. METHOD: The hemox-analyzer was used to generate the p50 and the oxygen-hemoglobin dissociation curves. MAIN OUTCOME MEASURES: The effect of different doses of sildenafil on the p50 values and shift of the oxygen-hemoglobin curve were the main outcome measures. RESULT: Sildenafil caused a statistically significant increase in the p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. CONCLUSION: Sildenafil caused a dose dependent increase in the release of oxygen from the erythrocytes as shown by the increased p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. Ellis SS and Pepple DJ. Sildenafil increases the p50 and shifts the oxygen hemoglobin dissociation curve to the right. PMID- 26553866 TI - [Health care based on cooperation between professionals and affected people]. AB - The purpose of this article is to support the need for a change of care, based on cooperation between those who provide care and those who receive it. This article develops the decisive factors for change: the investee cooperation, the reference in case management, the concept of recovery and terminal care, the reduction of suffering and the value of change reflected in the 'win-win'. In each of them a questioning of the current situation, a methodological analysis and an input of tools and consequences of the change is made. To conclude, the article incorporates the 'itinerary of shared care' as a resource and one of the ways to bring these changes to the reality of day-to-day care. PMID- 26553867 TI - Attitudes of therapists and other health professionals towards their LGB patients. AB - Lesbian, gay and bisexual people continue to suffer minority stress around the world, but particularly in Africa, the Middle East and Eastern Europe. This anti homosexual prejudice can enter into the therapist-client relationship and seriously damage the outcome of psychotherapy, particularly in instances where therapists regard their clients' sexuality as contributing to their psychological difficulties. This paper takes an historical perspective to research on the attitudes of a range of professionals who provide talking therapies or other types of psychological support to their clients who are lesbian, gay or bisexual. The nature and origins of prejudice, its effects on LGB clients, and how it might best be addressed are considered. Challenging the ethics and evidence base for treatments that purport to change sexual orientation, as well as asking heterosexual therapists to reflect on their own heteronormative assumptions, are crucial to effecting change and ensuring LGB people are treated equally to their heterosexual counterparts. PMID- 26553868 TI - Induction of Pluripotency in Astrocytes through a Neural Stem Cell-like State. AB - It remains controversial whether the routes from somatic cells to induced pluripotent stem cells (iPSCs) are related to the reverse order of normal developmental processes. Specifically, it remains unaddressed whether or not the differentiated cells become iPSCs through their original tissue stem cell-like state. Previous studies analyzing the reprogramming process mostly used fibroblasts; however, the stem cell characteristics of fibroblasts made it difficult to address this. Here, we generated iPSCs from mouse astrocytes, a type of glial cells, by three (OCT3/4, KLF4, and SOX2), two (OCT3/4 and KLF4), or four (OCT3/4, KLF4, and SOX2 plus c-MYC) factors. Sox1, a neural stem cell (NSC) specific transcription factor, is transiently up-regulated during reprogramming, and Sox1-positive cells become iPSCs. The up-regulation of Sox1 is essential for OCT3/4- and KLF4-induced reprogramming. Genome-wide analysis revealed that the gene expression profile of Sox1-expressing intermediate-state cells resembles that of NSCs. Furthermore, the intermediate-state cells are able to generate neurospheres, which can differentiate into both neurons and glial cells. Remarkably, during fibroblast reprogramming, neither Sox1 up-regulation nor an increase in neurogenic potential occurs. Our results thus demonstrate that astrocytes are reprogrammed through an NSC-like state. PMID- 26553869 TI - Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA. AB - HIV-1 infection results in a chronic illness because long-term highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/MUl were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-beta, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5' and 3' stems (TAR microRNAs) bound best to TLR7 and 8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF kappaB pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART. PMID- 26553871 TI - A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation. AB - Inflammasomes are high molecular weight protein complexes that assemble in the cytosol upon pathogen encounter. This results in caspase-1-dependent pro inflammatory cytokine maturation, as well as a special type of cell death, known as pyroptosis. The Nlrp3 inflammasome plays a pivotal role in pathogen defense, but at the same time, its activity has also been implicated in many common sterile inflammatory conditions. To this effect, several studies have identified Nlrp3 inflammasome engagement in a number of common human diseases such as atherosclerosis, type 2 diabetes, Alzheimer disease, or gout. Although it has been shown that known Nlrp3 stimuli converge on potassium ion efflux upstream of Nlrp3 activation, the exact molecular mechanism of Nlrp3 activation remains elusive. Here, we describe a genome-wide CRISPR/Cas9 screen in immortalized mouse macrophages aiming at the unbiased identification of gene products involved in Nlrp3 inflammasome activation. We employed a FACS-based screen for Nlrp3 dependent cell death, using the ionophoric compound nigericin as a potassium efflux-inducing stimulus. Using a genome-wide guide RNA (gRNA) library, we found that targeting Nek7 rescued macrophages from nigericin-induced lethality. Subsequent studies revealed that murine macrophages deficient in Nek7 displayed a largely blunted Nlrp3 inflammasome response, whereas Aim2-mediated inflammasome activation proved to be fully intact. Although the mechanism of Nek7 functioning upstream of Nlrp3 yet remains elusive, these studies provide a first genetic handle of a component that specifically functions upstream of Nlrp3. PMID- 26553870 TI - Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis. AB - Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-beta activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-beta1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF beta1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-beta bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases. PMID- 26553872 TI - Acid Ceramidase in Melanoma: EXPRESSION, LOCALIZATION, AND EFFECTS OF PHARMACOLOGICAL INHIBITION. AB - Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells. High AC expression was also observed in biopsies from human subjects with Stage II melanoma. Immunofluorescence studies revealed that the subcellular localization of AC differs between melanocytes (where it is found in both cytosol and nucleus) and melanoma cells (where it is primarily localized to cytosol). In addition to having high AC levels, melanoma cells generate lower amounts of ceramides than normal melanocytes do. This down-regulation in ceramide production appears to result from suppression of the de novo biosynthesis pathway. To test whether AC might contribute to melanoma cell proliferation, we blocked AC activity using a new potent (IC50 = 12 nM) and stable inhibitor. AC inhibition increased cellular ceramide levels, decreased sphingosine 1-phosphate levels, and acted synergistically with several, albeit not all, antitumoral agents. The results suggest that AC-controlled sphingolipid metabolism may play an important role in the control of melanoma proliferation. PMID- 26553873 TI - Nuclear Compartmentalization of Serine Racemase Regulates D-Serine Production: IMPLICATIONS FOR N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ACTIVATION. AB - D-Serine is a physiological co-agonist that activates N-methyl D-aspartate receptors (NMDARs) and is essential for neurotransmission, synaptic plasticity, and behavior. D-Serine may also trigger NMDAR-mediated neurotoxicity, and its dysregulation may play a role in neurodegeneration. D-Serine is synthesized by the enzyme serine racemase (SR), which directly converts L-serine to D-serine. However, many aspects concerning the regulation of D-serine production under physiological and pathological conditions remain to be elucidated. Here, we investigate possible mechanisms regulating the synthesis of D-serine by SR in paradigms relevant to neurotoxicity. We report that SR undergoes nucleocytoplasmic shuttling and that this process is dysregulated by several insults leading to neuronal death, typically by apoptotic stimuli. Cell death induction promotes nuclear accumulation of SR, in parallel with the nuclear translocation of GAPDH and Siah proteins at an early stage of the cell death process. Mutations in putative SR nuclear export signals (NESs) elicit SR nuclear accumulation and its depletion from the cytosol. Following apoptotic insult, SR associates with nuclear GAPDH along with other nuclear components, and this is accompanied by complete inactivation of the enzyme. As a result, extracellular D serine concentration is reduced, even though extracellular glutamate concentration increases severalfold. Our observations imply that nuclear translocation of SR provides a fail-safe mechanism to prevent or limit secondary NMDAR-mediated toxicity in nearby synapses. PMID- 26553874 TI - Sialic Acid on the Glycosylphosphatidylinositol Anchor Regulates PrP-mediated Cell Signaling and Prion Formation. AB - The prion diseases occur following the conversion of the cellular prion protein (PrP(C)) into disease-related isoforms (PrP(Sc)). In this study, the role of the glycosylphosphatidylinositol (GPI) anchor attached to PrP(C) in prion formation was examined using a cell painting technique. PrP(Sc) formation in two prion infected neuronal cell lines (ScGT1 and ScN2a cells) and in scrapie-infected primary cortical neurons was increased following the introduction of PrP(C). In contrast, PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc). Furthermore, the presence of desialylated PrP(C) inhibited the production of PrP(Sc) within prion infected cortical neurons and ScGT1 and ScN2a cells. The membrane rafts surrounding desialylated PrP(C) contained greater amounts of sialylated gangliosides and cholesterol than membrane rafts surrounding PrP(C). Desialylated PrP(C) was less sensitive to cholesterol depletion than PrP(C) and was not released from cells by treatment with glimepiride. The presence of desialylated PrP(C) in neurons caused the dissociation of cytoplasmic phospholipase A2 from PrP-containing membrane rafts and reduced the activation of cytoplasmic phospholipase A2. These findings show that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. These results suggest that pharmacological modification of GPI glycosylation might constitute a novel therapeutic approach to prion diseases. PMID- 26553875 TI - DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites. AB - The DISC1 protein is implicated in major mental illnesses including schizophrenia, depression, bipolar disorder, and autism. Aberrant mitochondrial dynamics are also associated with major mental illness. DISC1 plays a role in mitochondrial transport in neuronal axons, but its effects in dendrites have yet to be studied. Further, the mechanisms of this regulation and its role in neuronal development and brain function are poorly understood. Here we have demonstrated that DISC1 couples to the mitochondrial transport and fusion machinery via interaction with the outer mitochondrial membrane GTPase proteins Miro1 and Miro2, the TRAK1 and TRAK2 mitochondrial trafficking adaptors, and the mitochondrial fusion proteins (mitofusins). Using live cell imaging, we show that disruption of the DISC1-Miro-TRAK complex inhibits mitochondrial transport in neurons. We also show that the fusion protein generated from the originally described DISC1 translocation (DISC1-Boymaw) localizes to the mitochondria, where it similarly disrupts mitochondrial dynamics. We also show by super resolution microscopy that DISC1 is localized to endoplasmic reticulum contact sites and that the DISC1-Boymaw fusion protein decreases the endoplasmic reticulum mitochondria contact area. Moreover, disruption of mitochondrial dynamics by targeting the DISC1-Miro-TRAK complex or upon expression of the DISC1-Boymaw fusion protein impairs the correct development of neuronal dendrites. Thus, DISC1 acts as an important regulator of mitochondrial dynamics in both axons and dendrites to mediate the transport, fusion, and cross-talk of these organelles, and pathological DISC1 isoforms disrupt this critical function leading to abnormal neuronal development. PMID- 26553877 TI - Spectroscopic and Kinetic Properties of the Molybdenum-containing, NAD+-dependent Formate Dehydrogenase from Ralstonia eutropha. AB - We have examined the rapid reaction kinetics and spectroscopic properties of the molybdenum-containing, NAD(+)-dependent FdsABG formate dehydrogenase from Ralstonia eutropha. We confirm previous steady-state studies of the enzyme and extend its characterization to a rapid kinetic study of the reductive half reaction (the reaction of formate with oxidized enzyme). We have also characterized the electron paramagnetic resonance signal of the molybdenum center in its Mo(V) state and demonstrated the direct transfer of the substrate Calpha hydrogen to the molybdenum center in the course of the reaction. Varying temperature, microwave power, and level of enzyme reduction, we are able to clearly identify the electron paramagnetic resonance signals for four of the iron/sulfur clusters of the enzyme and find suggestive evidence for two others; we observe a magnetic interaction between the molybdenum center and one of the iron/sulfur centers, permitting assignment of this signal to a specific iron/sulfur cluster in the enzyme. In light of recent advances in our understanding of the structure of the molybdenum center, we propose a reaction mechanism involving direct hydride transfer from formate to a molybdenum-sulfur group of the molybdenum center. PMID- 26553878 TI - Detection and characterization of intracranial aneurysms: a 10-year multidetector CT angiography experience in a large center. AB - BACKGROUND: CT angiography (CTA) is increasingly used for the detection, characterization, and follow-up of intracranial aneurysms. A lower threshold to request a CT angiogram may render a patient population that differs from previous studies primarily evaluated with conventional angiography. Our objective was to broaden our knowledge of the factors associated with aneurysm rupture and patient mortality in this population. METHODS: All CTA studies performed over a 10-year period at a large neurovascular referral center were reviewed for the presence of an intracranial aneurysm. Patient demographics, mortality, CTA indication, aneurysm location, size, and rupture status were recorded. RESULTS: 2927 patients with aneurysms were identified among 29 003 CTAs. 17% of the aneurysms were ruptured at the time of imaging, 24% of aneurysms were incidentally identified, and multiple aneurysms were identified in 34% of patients. Aneurysms most commonly arose from the supraclinoid internal carotid artery (22%), the middle cerebral artery (18%), and the anterior communicating artery (13%). Male sex, age <50 years, aneurysms >6 mm, and aneurysms arising from the anterior communicating artery, posterior communicating artery, or the posterior circulation were independent predictors of aneurysm rupture. Independent mortality predictors included male sex, posterior circulation aneurysms, intraventricular hemorrhage, and intraparenchymal hemorrhage. CONCLUSIONS: These results indicate that aneurysms detected on CTA that arise from the anterior communicating artery, posterior communicating artery, or the posterior circulation, measure >6 mm in size, occur in men, and in patients aged <50 years are associated with rupture. PMID- 26553876 TI - Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity. AB - Phospholipids (PLs) are unusual signaling hormones sensed by the nuclear receptor liver receptor homolog-1 (LRH-1), which has evolved a novel allosteric pathway to support appropriate interaction with co-regulators depending on ligand status. LRH-1 plays an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of metabolic and neoplastic diseases. Although the prospect of modulating LRH-1 via small molecules is exciting, the molecular mechanism linking PL structure to transcriptional co-regulator preference is unknown. Previous studies showed that binding to an activating PL ligand, such as dilauroylphosphatidylcholine, favors LRH-1's interaction with transcriptional co-activators to up-regulate gene expression. Both crystallographic and solution-based structural studies showed that dilauroylphosphatidylcholine binding drives unanticipated structural fluctuations outside of the canonical activation surface in an alternate activation function (AF) region, encompassing the beta-sheet-H6 region of the protein. However, the mechanism by which dynamics in the alternate AF influences co-regulator selectivity remains elusive. Here, we pair x-ray crystallography with molecular modeling to identify an unexpected allosteric network that traverses the protein ligand binding pocket and links these two elements to dictate selectivity. We show that communication between the alternate AF region and classical AF2 is correlated with the strength of the co-regulator interaction. This work offers the first glimpse into the conformational dynamics that drive this unusual PL mediated nuclear hormone receptor activation. PMID- 26553879 TI - Successful endovascular stroke therapy in a 103-year-old woman. AB - People older than 80 years of age constitute the most rapidly growing age group in the world. Several trials confirming superior efficacy of endovascular therapy did not have an upper age limit and showed favorable treatment effects, regardless of age. Current American Heart Association/American Stroke Association guidelines do not restrict treatment based on age as long as other eligibility criteria are met. A 103-year-old woman presented 2 h after stroke onset secondary to a left internal carotid artery terminus (ICA-T) occlusion. Admission National Institutes of Health Stoke Scale (NIHSS) score was 38, with no early ischemic changes on imaging, pre-stroke modified Rankin Scale score was 0, and she lived independently with minimal help. After initiation of intravenous thrombolysis, the patient underwent successful mechanical thrombectomy with Thombosis in Cerebral Infaction-3 recanalization. She showed remarkable recovery (NIHSS score of 1 at 48 h). Stroke onset to recanalization was 3 h 40 min. Our objective in documenting the oldest patient to successfully undergo stroke intervention is to corroborate that with the current evidence, appropriate patients undergoing rapid treatment may allow us to advance the limits of endovascular therapy. PMID- 26553880 TI - Dermatitis caused by metal allergy after coil embolization for unruptured cerebral aneurysm. AB - We report a rare case of metal-induced dermatitis after coil embolization for cerebral aneurysm. A 51-year-old woman experienced a rash around the lips and neck 3 weeks after coil embolization. Judging from the clinical course and results of several patch tests, platinum coils were considered to have induced the dermatitis. Symptoms were relieved with administration of oral steroids. This represents the first report of metal-induced dermatitis after neuroendovascular treatment. The possibility of metal allergy was difficult to suspect preoperatively. However, early evaluation and referral are important when skin symptoms are observed postoperatively. PMID- 26553881 TI - A study of cytocompatibility and degradation of iron-based biodegradable materials. AB - Biodegradable metallic implants are of significant importance in the replacement of bones or the repair of bone defects. Iron-phosphate-coated carbonyl iron powder (Fe/P) was prepared by the phosphating method. Moreover, Fe/P-Mn alloy was produced by sintering the Fe/P powder mixed with manganese powder. Bare carbonyl iron samples and the Fe/P and Fe/P-Mn sintered samples were evaluated for their microstructure, cytotoxicity, and hemocompatibility. The microstructure of the sintered samples was examined using an optical microscope and scanning electron microscopic analysis. Corrosion behavior was evaluated by potentiodynamic polarization in Hank's solution. The in vitro biocompatibilities were investigated by cytotoxicity and hemolysis tests. The results obtained demonstrate that the addition of Mn resulted in higher surface inhomogeneity, porosity and roughness as well as in increased cytotoxicity. The phosphate coating has a moderately negative effect on the cytotoxicity. The corrosion rates determined from Tafel diagrams were ordered in the following sequence: Fe/P-Mn, Fe, Fe/P from high to low. The hemocompatibility of experimental samples was ordered in the following sequence: Fe/P, Fe/P-Mn, Fe from high to low. All samples were found to be hemocompatible. PMID- 26553882 TI - Synthesis and characterization of an in situ forming hydrogel using tyramine conjugated high methoxyl gum tragacanth. AB - In this study, an enzyme catalyzed in situ forming hydrogel based on tyramine conjugated high methoxyl content gum tragacanth (TA-HMGT) was prepared and characterized. TA-HMGT was synthesized via heterogeneous ammonolysis of methyl ester groups of HMGT. Then, the hydrogel was prepared via horseradish peroxidase catalyzed coupling reaction in the presence of hydrogen peroxide. Hydrogel properties, such as gelation time, swelling/degradation behavior and rheological properties could be adjusted by tuning the gelation parameters and extent of tyramine conjugation. This system was a soft elastic hydrogel with appropriate biocompatibility. The fast gelation of the hydrogel is desirable for clinical applications. Also, in vitro bovine serum albumin release from the synthesized hydrogel showed good release profile with limited burst release. PMID- 26553883 TI - Vitamin D and Dental Caries in Children. AB - The purpose of this study was to assess the relationship between vitamin D status and dental caries in Canadian school-aged children participating in the Canadian Health Measures Survey (CHMS). The CHMS was a national cross-sectional study involving physical assessments, laboratory analysis, and interviews. Analysis was restricted to data for 1,017 children 6 to 11 y of age. Outcome variables included the presence of caries and overall total caries score (dmft/DMFT index). Levels of 25-hydroxyvitamin D (25(OH)D) were measured from serum samples obtained from participants. Bivariate analysis, logistic regression for the presence of caries, and multiple linear regression for total caries scores were used. Significance was set at P <= 0.05. Overall, 56.4% of children experienced caries, and the mean dmft/DMFT score was 2.47 (95% CI 2.09 to 2.84). The unadjusted odds of children with 25(OH)D levels >=75 nmol/L having experienced caries was 0.57 (95% CI 0.39 to 0.82), while the odds for caries at the >=50 nmol/L level was 0.56 (95% CI 0.39 to 0.89). After controlling for other covariates, backward logistic regression revealed that the presence of caries was significantly associated with 25(OH) levels <75 nmol/L and <50 nmol/L, lower household education, not brushing twice daily, and yearly visits to the dentist. Similarly, multiple linear regression revealed that total dmft/DMFT caries scores were also associated with 25(OH)D concentrations <75 nmol/L, not brushing twice daily, lower household education, and yearly visits to the dentist. Data from a cross sectional, nationally representative sample of Canadian children suggest that there is an association between caries and lower serum vitamin D. Improving children's vitamin D status may be an additional preventive consideration to lower the risk for caries. PMID- 26553884 TI - The Shape of the Dose-Response Relationship between Sugars and Caries in Adults. AB - Dental caries is considered a diet-mediated disease, as sugars are essential in the caries process. However, some gaps in knowledge about the sugars-caries relationship still need addressing. This longitudinal study aimed to explore 1) the shape of the dose-response association between sugars intake and caries in adults, 2) the relative contribution of frequency and amount of sugars intake to caries levels, and 3) whether the association between sugars intake and caries varies by exposure to fluoride toothpaste. We used data from 1,702 dentate adults who participated in at least 2 of 3 surveys in Finland (Health 2000, 2004/05 Follow-up Study of Adults' Oral Health, and Health 2011). Frequency and amount of sugars intake were measured with a validated food frequency questionnaire. The DMFT index was the repeated outcome measure. Data were analyzed with fractional polynomials and linear mixed effects models. None of the 43 fractional polynomials tested provided a better fit to the data than the simpler linear model. In a mutually adjusted linear mixed effects model, the amount of, but not the frequency of, sugars intake was significantly associated with DMFT throughout the follow-up period. Furthermore, the longitudinal association between amount of sugars intake and DMFT was weaker in adults who used fluoride toothpaste daily than in those using it less often than daily. The findings of this longitudinal study among Finnish adults suggest a linear dose-response relationship between sugars and caries, with amount of intake being more important than frequency of ingestion. Also, daily use of fluoride toothpaste reduced but did not eliminate the association between amount of sugars intake and dental caries. PMID- 26553885 TI - Topography Influences Adherent Cell Regulation of Osteoclastogenesis. AB - The importance of osteoclast-mediated bone resorption in the process of osseointegration has not been widely considered. In this study, cell culture was used to investigate the hypothesis that the function of implant-adherent bone marrow stromal cells (BMSCs) in osteoclastogenesis is influenced by surface topography. BMSCs isolated from femur and tibia of Sprague-Dawley rats were seeded onto 3 types of titanium surfaces (smooth, micro, and nano) and a control surface (tissue culture plastic) with or without osteogenic supplements. After 3 to 14 d, conditioned medium (CM) was collected. Subsequently, rat bone marrow derived macrophages (BMMs) were cultured in media supplemented with soluble receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as well as BMSC CM from each of the 4 surfaces. Gene expression levels of soluble RANKL, osteoprotegerin, tumor necrosis factor alpha, and M-CSF in cultured BMSCs at different time points were measured by real-time polymerase chain reaction. The number of differentiated osteoclastic cells was determined after tartrate-resistant acid phosphatase staining. Analysis of variance and t test were used for statistical analysis. The expression of prominent osteoclast promoting factors tumor necrosis factor alpha and M-CSF was increased by BMSCs cultured on both micro- and nanoscale titanium topographies (P < 0.01). BMSC CM contained a heat-labile factor that increased BMMs osteoclastogenesis. CM from both micro- and nanoscale surface-adherent BMSCs increased the osteoclast number (P < 0.01). Difference in surface topography altered BMSC phenotype and influenced BMM osteoclastogenesis. Local signaling by implant-adherent cells at the implant-bone interface may indirectly control osteoclastogenesis and bone accrual around endosseous implants. PMID- 26553886 TI - Analysis of deformity in scaphoid non-unions using two- and three-dimensional imaging. AB - Pre-operative assessment of the deformity in scaphoid non-unions influences surgical decision-making. To characterize deformity, we used three-dimensional computed tomographic modelling in 28 scaphoid non-unions, and quantified bone loss, dorsal osteophyte volume and flexion deformity. We further related these three-dimensional parameters to the intrascaphoid and capitate-lunate angles, and stage of scaphoid non-union advanced collapse assessed on conventional two dimensional images and to the chosen surgical procedure. Three-dimensional flexion deformity (mean 26 degrees ) did not correlate with intrascaphoid and capitate-lunate angles. Osteophyte volume was positively correlated with bone loss and stage of scaphoid non-union advanced collapse. Osteophyte volume and bone loss increased over time. Three-dimensional modelling enables the quantification of bone loss and osteophyte volume, which may be valuable parameters in the characterization of deformity and subsequent decision-making about treatment, when taken in addition to the clinical aspects and level of osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Level IV. PMID- 26553887 TI - Understanding the Context for Long-Term Care Planning. AB - Evolving family structure and economic conditions may affect individuals' ability and willingness to plan for future long-term care (LTC) needs. We applied life course constructs to analyze focus group data from a study of family decision making about LTC insurance. Participants described how past exposure to caregiving motivated them to engage in LTC planning; in contrast, child rearing discouraged LTC planning. Perceived institutional and economic instability drove individuals to regard financial LTC planning as either a wise precaution or another risk. Perceived economic instability also shaped opinions that adult children are ill-equipped to support parents' LTC. Despite concerns about viability of social insurance programs, some participants described strategies to maximize gains from them. Changing norms around aging and family roles also affected expectations of an active older age, innovative LTC options, and limitations to adult children's involvement. Understanding life course context can inform policy efforts to encourage LTC planning. PMID- 26553888 TI - CORRECTION. Learning from no-fault treatment injury claims to improve the safety of older patients. PMID- 26553889 TI - Perspectives in Primary Care: Values-Driven Leadership is Essential in Health Care. PMID- 26553890 TI - Impact of the Prevalence of Concordant and Discordant Conditions on the Quality of Diabetes Care in Family Practices in England. AB - PURPOSE: The purpose of this study was to examine the association between the prevalence of both diabetes-concordant and diabetes-discordant conditions and the quality of diabetes care at the family practice level in England. We hypothesized that the prevalence of concordant (or discordant) conditions would be associated with better (or worse) quality of diabetes care. METHODS: We conducted a cross sectional study using practice-level data (7,884 practices). We estimated the practice-level prevalence of diabetes and 15 other chronic conditions, which were classified as diabetes concordant (ie, with the same pathophysiologic risk profile and therefore more likely to be part of the same management plan) or diabetes discordant (ie, not directly related in either their pathogenesis or management). We measured quality of diabetes care with diabetes-specific indicators (8 processes and 3 intermediate outcomes of care). We used linear regression models to quantify the effect of the prevalence of the conditions on aggregate achievement rate for quality of diabetes care. RESULTS: Consistent with the proposed model, the prevalence rates of 4 of 7 concordant conditions (obesity, chronic kidney disease, atrial fibrillation, heart failure) were positively associated with quality of diabetes care. Similarly, negative associations were observed as predicted for 2 of the 8 discordant conditions (epilepsy, mental health). Observations for other concordant and discordant conditions did not match predictions in the hypothesized model. CONCLUSIONS: The quality of diabetes care provided in English family practices is associated with the prevalence of other major chronic conditions at the practice level. The nature and direction of the observed associations cannot be fully explained by the concordant-discordant model. PMID- 26553891 TI - Case Management in Primary Care for Frequent Users of Health Care Services With Chronic Diseases: A Qualitative Study of Patient and Family Experience. AB - PURPOSE: Although case management (CM) is increasingly being implemented to address the complex needs of vulnerable clienteles, few studies have examined the patient experience of CM. This study aimed to examine the experience of patients and their family members with care integration as part of a primary care CM intervention. Patients in the study were frequent users of health care services who had chronic diseases. METHODS: A descriptive, qualitative approach was conducted involving 25 patients and 8 of their family members. Data were collected through in-depth interviews of the patients and 2 focus groups of family members and were analyzed thematically. RESULTS: While some participants did not fully understand the CM intervention and a few believed that it involved too many appointments, the CM nurses were patients' preferred contact with primary care. The nurses actively involved the patients in developing and carrying out their individualized services plans (ISPs) with other health care partners. Patients felt that their needs were taken into consideration, especially regarding access to the health care system. The case manager facilitated access to information as well as communication and coordination among health care and community partners. This improved communication comforted the patients and nurtured a relationship of trust. Participants were actively involved in decision-making. Their ISPs helped them know where they were going and improved transitions between services. CONCLUSIONS: The experience of patients and family members was overall very positive regarding care integration. They reported improved access, communication, coordination, and involvement in decision-making as well as better health care transitions. PMID- 26553893 TI - The Identity Crisis of Osteoarthritis in General Practice: A Qualitative Study Using Video-Stimulated Recall. AB - PURPOSE: Patients and doctors report marked disenchantment with primary care consultation experiences relating to osteoarthritis. This study aimed to observe and analyze interactions between general practitioners (GPs) and patients presenting with osteoarthritis (OA) to identify how to improve care for OA. METHODS: We conducted an observational study in general practices in the United Kingdom using video-recorded real-life consultations of unselected patients and their GPs. Postconsultation interviews were conducted using video-stimulated recall. Both consultations and interviews were analyzed thematically. RESULTS: Three key themes were identified in an analysis of 19 OA consultations and the matched GP and patient interviews: complexity, dissonance, and prioritization. The topic of osteoarthritis arises in the consultation in complex contexts of multimorbidity and multiple, often not explicit, patient agendas. Dissonance between patient and doctor was frequently observed and reported; this occurred when GPs normalized symptoms of OA as part of life and reassured patients who were not seeking reassurance. GPs used wear and tear in preference to osteoarthritis or didn't name the condition at all. GPs subconsciously made assumptions that patients did not consider OA a priority and that symptoms raised late in the consultation were not troublesome. CONCLUSIONS: The lack of a clear illness profile results in confusion between patients and doctors about what OA is and its priority in the context of multimorbidity. This study highlights generic communication issues regarding the potential negative consequences of unsought reassurance and the importance of validation of symptoms and raises new arguments for tackling OA's identity crisis by developing a clearer medical language with which to explain OA. PMID- 26553892 TI - Roles of Clinician, Patient, and Community Characteristics in the Management of Pediatric Upper Respiratory Tract Infections. AB - PURPOSE: Prior studies have evaluated factors predictive of inappropriate antibiotic prescription for upper respiratory tract infections (URIs). Community factors, however, have not been examined. The aim of this study was to evaluate the roles of patient, clinician, and community factors in predicting appropriate management of URIs in children. METHODS: We used a novel database exchange, linking electronic health record data with community statistics, to identify all patients aged 3 months to 18 years in whom URI was diagnosed in the period from 2007 to 2012. We followed the Healthcare Effectiveness Data and Information Set (HEDIS) quality measurement titled "Appropriate treatment for children with upper respiratory infection" to determine the rate of appropriate management of URIs. We then stratified data across individual and community characteristics and used multiple logistic regression modeling to identify variables that independently predicted antibiotic prescription. RESULTS: Of 20,581 patients, the overall rate for appropriate management for URI was 93.5%. Family medicine clinicians (AOR = 1.5; 95% CI 1.31, 1.71; reference = pediatric clinicians), urgent care clinicians (AOR = 2.23; 95% CI 1.93, 2.57; reference = pediatric clinicians), patients aged 12 to 18 years (AOR = 1.44; 95% CI 1.25, 1.67; reference = age 3 months to 4 years), and patients of white race/ ethnicity (AOR = 1.83; 95% CI 1.41, 2.37; reference = black non-Hispanic) were independently predictive of antibiotic prescription. No community factors were independently predictive of antibiotic prescription. CONCLUSIONS: Results correlate with prior studies in which non pediatric clinicians and white race/ethnicity were predictive of antibiotic prescription, while association with older patient age has not been previously reported. Findings illustrate the promise of linking electronic health records with community data to evaluate health care disparities. PMID- 26553894 TI - Effectiveness of a Multifaceted Intervention for Potentially Inappropriate Prescribing in Older Patients in Primary Care: A Cluster-Randomized Controlled Trial (OPTI-SCRIPT Study). AB - PURPOSE: Potentially inappropriate prescribing (PIP) is common in older people and can result in increased morbidity, adverse drug events, and hospitalizations. The OPTI-SCRIPT study (Optimizing Prescribing for Older People in Primary Care, a cluster-randomized controlled trial) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care. METHODS: We conducted a cluster randomized controlled trial among 21 general practitioner practices and 196 patients with PIP. Intervention participants received a complex, multifaceted intervention incorporating academic detailing; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options; and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions. We performed intention-to-treat analysis using random-effects regression. RESULTS: All 21 practices and 190 patients were followed. At intervention completion, patients in the intervention group had significantly lower odds of having PIP than patients in the control group (adjusted odds ratio = 0.32; 95% CI, 0.15-0.70; P = .02). The mean number of PIP drugs in the intervention group was 0.70, compared with 1.18 in the control group (P = .02). The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion, but this difference was not significant (incidence rate ratio = 0.71; 95% CI, 0.50-1.02; P = .49). The intervention was effective in reducing proton pump inhibitor prescribing (adjusted odds ratio = 0.30; 95% CI, 0.14-0.68; P = .04). CONCLUSIONS: The OPTI SCRIPT intervention incorporating academic detailing with a pharmacist, and a review of medicines with web-based pharmaceutical treatment algorithms, was effective in reducing PIP, particularly in modifying prescribing of proton pump inhibitors, the most commonly occurring PIP drugs nationally. PMID- 26553895 TI - Integrating Quantitative and Qualitative Results in Health Science Mixed Methods Research Through Joint Displays. AB - PURPOSE: Mixed methods research is becoming an important methodology to investigate complex health-related topics, yet the meaningful integration of qualitative and quantitative data remains elusive and needs further development. A promising innovation to facilitate integration is the use of visual joint displays that bring data together visually to draw out new insights. The purpose of this study was to identify exemplar joint displays by analyzing the various types of joint displays being used in published articles. METHODS: We searched for empirical articles that included joint displays in 3 journals that publish state-of-the-art mixed methods research. We analyzed each of 19 identified joint displays to extract the type of display, mixed methods design, purpose, rationale, qualitative and quantitative data sources, integration approaches, and analytic strategies. Our analysis focused on what each display communicated and its representation of mixed methods analysis. RESULTS: The most prevalent types of joint displays were statistics-by-themes and side-by-side comparisons. Innovative joint displays connected findings to theoretical frameworks or recommendations. Researchers used joint displays for convergent, explanatory sequential, exploratory sequential, and intervention designs. We identified exemplars for each of these designs by analyzing the inferences gained through using the joint display. Exemplars represented mixed methods integration, presented integrated results, and yielded new insights. CONCLUSIONS: Joint displays appear to provide a structure to discuss the integrated analysis and assist both researchers and readers in understanding how mixed methods provides new insights. We encourage researchers to use joint displays to integrate and represent mixed methods analysis and discuss their value. PMID- 26553896 TI - Transitional Care for Patients With Congestive Heart Failure: A Systematic Review and Meta-Analysis. AB - PURPOSE: We aimed to determine the impact of transitional care interventions (TCIs) on acute health service use by patients with congestive heart failure in primary care and to identify the most effective TCIs and their optimal duration. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials, searching the Medline, PsycInfo, EMBASE, and Cochrane Library databases. We performed a meta-analysis to assess the impact of TCI on all-cause hospital readmissions and emergency department (ED) visits. We developed a taxonomy of TCIs based on intensity and assessed the methodologic quality of the trials. We calculated the relative risk (RR) and a 95% confidence interval for each outcome. We conducted a stratified analysis to identify the most effective TCIs and their optimal duration. RESULTS: We identified 41 randomized controlled trials. TCIs significantly reduced risks of readmission and ED visits by 8% and 29%, respectively (relative risk = 0.92; 95% CI, 0.87-0.98; P = .006 and relative risk = 0.71; 95% CI, 0.51-0.98; P = .04). High-intensity TCIs (combining home visits with telephone followup, clinic visits, or both) reduced readmission risk regardless of the duration of follow-up. Moderate-intensity TCIs were efficacious if implemented for a longer duration (at least 6 months). In contrast, low intensity TCIs, entailing only followup in outpatient clinics or telephone follow up, were not efficacious. CONCLUSIONS: Clinicians and managers who implement TCIs in primary care can incorporate these results with their own health care context to determine the optimal balance between intensity and duration of TCIs. High intensity interventions seem to be the best option. Moderate-intensity interventions implemented for 6 months or longer may be another option. PMID- 26553898 TI - Fatal Consequences: Obstructive Sleep Apnea in a Train Engineer. AB - This special report describes the findings of the National Transportation Safety Board's investigation into the probable cause of the derailment of a Metro-North passenger train in the Bronx, New York on December 1, 2013, that resulted in 4 deaths and injuries to 59 additional persons. A key finding in the medical investigation was the engineer's post-accident diagnosis of severe, obstructive sleep apnea, and the probable cause of the accident was determined to be the result of the engineer having fallen asleep while operating the train. This accident highlights the importance of screening, evaluating, and ensuring adequate treatment of obstructive sleep apnea, particularly among patients working in positions where impairment of physical or cognitive function or sudden incapacitation may result in serious harm to the public. PMID- 26553897 TI - The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review. AB - PURPOSE: Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS: We performed a meta analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS: The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). CONCLUSIONS: Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID- 26553899 TI - The Untaught Lesson. AB - My fellow physician and friend died from a rare type of cancer. She was a model for me in many respects. She showed me how to cope with a chronic disease together with a demanding professional life, yet she left me without any comfort or guidelines on how to contend with a terminal disease. This story is a reflection on my frustration and disappointment with my friend's final choices that prevented us from processing our feelings and sharing our deepest thoughts. The story includes reflections and insights about our ability to understand and accept the preferences of patients and others close to us. PMID- 26553900 TI - OUR TIME IS NOW: AAFP PRESIDENT PLEDGES TO FIGHT FOR RESPECT AND RESOURCES. PMID- 26553901 TI - PISACANO LEADERSHIP FOUNDATION NAMES 2015 PISACANO SCHOLARS. PMID- 26553902 TI - PARTNERING FOR TRANSFORMATION: A MENU OF MANY POINTS OF ENTRY FOR YOUR DEPARTMENT. PMID- 26553903 TI - STFM LAUNCHES INTERPROFESSIONAL LEADING CHANGE FELLOWSHIP. PMID- 26553904 TI - THE NATIONAL GRADUATE SURVEY FOR FAMILY MEDICINE. PMID- 26553905 TI - NAPCRG ANNUAL MEETING DISTINGUISHED PAPERS. PMID- 26553906 TI - Low-dose versus high-dose fish oil for pain reduction and function improvement in patients with knee osteoarthritis. PMID- 26553908 TI - The effects of malnutrition on cardiac function in African children. AB - OBJECTIVE: Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. DESIGN: Prospective cross sectional study. SETTING: Public referral hospital in Blantyre, Malawi. PATIENTS: We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. RESULTS: Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. CONCLUSIONS: In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. PMID- 26553907 TI - Management of Crohn's disease. AB - Crohn's disease (CD) is rapidly increasing in children so an up to date knowledge of diagnosis, investigation and management is essential. Exclusive enteral nutrition is the first line treatment for active disease. The vast majority of children will need immunosuppressant treatment and around 20% will need treatment with biologics. Recent guidelines have helped make best use of available therapies. PMID- 26553910 TI - Question 2: Can paediatric early warning systems predict serious clinical deterioration in paediatric inpatients? PMID- 26553909 TI - Management of ulcerative colitis. AB - Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects. PMID- 26553911 TI - Service use in children aged 6-8 years with attention deficit hyperactivity disorder. AB - OBJECTIVE: This study investigated prevalence, types and predictors of professional service use in families of children identified with attention deficit hyperactivity disorder (ADHD) in the community. DESIGN: SETTING: children with ADHD were identified through 43 schools using parent and teacher screening questionnaires (Conners 3 ADHD Index) followed by case confirmation using the Diagnostic Interview Schedule for Children Version IV. Parents completed a survey about professional service use in the last 12 months. MAIN OUTCOME MEASURES: data on variables potentially associated with service use were collected from parents (interview and questionnaires), teachers (questionnaires) and children (direct assessment). Logistic regression was used to examine predictors of service use in univariate and multivariable analyses. RESULTS: The sample comprised 179 children aged 6-8 years with ADHD. Over one-third (37%) had not received professional services in the last 12 months. The strongest predictors of service use were older child age (adjusted OR=3.0, 95% CI 1.0 to 8.9, p=0.05), and the degree to which the child's behaviour impacted on the family (adjusted OR=2.0, 95% CI 1.3 to 3.3, p=0.007), after controlling for ADHD subtype and severity, externalising comorbidities, academic achievement and parent-reported impairment. CONCLUSIONS: A substantial proportion of children with ADHD are not accessing professional services. Our findings suggest that the child's age and the impact of the child's behaviour on the family are the strongest predictors of service use. Given the demonstrated benefits from various interventions in ADHD, there is a need to improve case identification and referral for services. PMID- 26553912 TI - Conflict in a paediatric hospital: a prospective mixed-method study. AB - BACKGROUND: Conflict in healthcare is a well-recognised but under-examined phenomenon. Little is known about the prevalence and causes of conflict across paediatric specialties. OBJECTIVE: To report the frequency and characteristics of conflict in a paediatric hospital. DESIGN AND SETTING: An explanatory sequential mixed-method approach was adopted. A bespoke questionnaire recorded frequency, severity, cause and staff involved in conflict prospectively. Data were recorded for the same two 12-week periods in 2013 and 2014, in one UK children's teaching hospital. Data were analysed using descriptive statistics and correlation, the findings of which informed the construction of a semistructured interview schedule. Qualitative interviews were conducted with six key informant healthcare professionals to aid data interpretation; interviews were analysed thematically. RESULTS: 136 individual episodes of conflict were reported. The three most common causes were 'communication breakdown', 'disagreements about treatment' and 'unrealistic expectations'. Over 448 h of healthcare professional time was taken up by these conflicts; most often staff nurses, consultants, doctors in training and matrons. The mean severity rating was 4.9 out of 10. Qualitative interviews revealed consensus regarding whether conflicts were ranked as low, medium or high severity, and explanations regarding why neurology recorded the highest number of conflicts in the observed period. CONCLUSIONS: Conflict is prevalent across paediatric specialties, and particularly in neurology, general paediatrics and neonatology. Considerable staff time is taken in managing conflict, indicating a need to focus resources on supporting staff to resolve conflict, notably managing communication breakdown. PMID- 26553913 TI - CopyNumber450kCancer: baseline correction for accurate copy number calling from the 450k methylation array. AB - The Illumina Infinium HumanMethylation450 BeadChip (450k) is widely used for the evaluation of DNA methylation levels in large-scale datasets, particularly in cancer. The 450k design allows copy number variant (CNV) calling using existing bioinformatics tools. However, in cancer samples, numerous large-scale aberrations cause shifting in the probe intensities and thereby may result in erroneous CNV calling. Therefore, a baseline correction process is needed. We suggest the maximum peak of probe segment density to correct the shift in the intensities in cancer samples. AVAILABILITY AND IMPLEMENTATION: CopyNumber450kCancer is implemented as an R package. The package with examples can be downloaded at http://cran.r-project.org CONTACT: nour.marzouka@medsci.uu.se SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26553914 TI - Using Cox cluster processes to model latent pulse location patterns in hormone concentration data. AB - Many hormones, including stress hormones, are intermittently secreted as pulses. The pulsatile location process, describing times when pulses occur, is a regulator of the entire stress system. Characterizing the pulse location process is particularly difficult because the pulse locations are latent; only hormone concentration at sampled times is observed. In addition, for stress hormones the process may change both over the day and relative to common external stimuli. This potentially results in clustering in pulse locations across subjects. Current approaches to characterizing the pulse location process do not capture subject-to-subject clustering in locations. Here we show how a Bayesian Cox cluster process may be adapted as a model of the pulse location process. We show that this novel model of pulse locations is capable of detecting circadian rhythms in pulse locations, clustering of pulse locations between subjects, and identifying exogenous controllers of pulse events. We integrate our pulse location process into a model of hormone concentration, the observed data. A spatial birth-and-death Markov chain Monte Carlo algorithm is used for estimation. We exhibit the strengths of this model on simulated data and adrenocorticotropic and cortisol data collected to study the stress axis in depressed and non-depressed women. PMID- 26553915 TI - A decision-theoretic phase I-II design for ordinal outcomes in two cycles. AB - This paper is motivated by a phase I-II clinical trial of a targeted agent for advanced solid tumors. We study a stylized version of this trial with the goal to determine optimal actions in each of two cycles of therapy. A design is presented that generalizes the decision-theoretic two-cycle design of Lee and others (2015. Bayesian dose-finding in two treatment cycles based on the joint utility of efficacy and toxicity. Journal of the American Statistical Association, to appear) to accommodate ordinal outcomes. Backward induction is used to jointly optimize the actions taken for each patient in each of the two cycles, with the second action accounting for the patient's cycle 1 dose and outcomes. A simulation study shows that simpler designs obtained by dichotomizing the ordinal outcomes either perform very similarly to the proposed design, or have much worse performance in some scenarios. We also compare the proposed design with the simpler approaches of optimizing the doses in each cycle separately, or ignoring the distinction between cycles 1 and 2. PMID- 26553916 TI - Fast, fully Bayesian spatiotemporal inference for fMRI data. AB - We propose a spatial Bayesian variable selection method for detecting blood oxygenation level dependent activation in functional magnetic resonance imaging (fMRI) data. Typical fMRI experiments generate large datasets that exhibit complex spatial and temporal dependence. Fitting a full statistical model to such data can be so computationally burdensome that many practitioners resort to fitting oversimplified models, which can lead to lower quality inference. We develop a full statistical model that permits efficient computation. Our approach eases the computational burden in two ways. We partition the brain into 3D parcels, and fit our model to the parcels in parallel. Voxel-level activation within each parcel is modeled as regressions located on a lattice. Regressors represent the magnitude of change in blood oxygenation in response to a stimulus, while a latent indicator for each regressor represents whether the change is zero or non-zero. A sparse spatial generalized linear mixed model captures the spatial dependence among indicator variables within a parcel and for a given stimulus. The sparse SGLMM permits considerably more efficient computation than does the spatial model typically employed in fMRI. Through simulation we show that our parcellation scheme performs well in various realistic scenarios. Importantly, indicator variables on the boundary between parcels do not exhibit edge effects. We conclude by applying our methodology to data from a task-based fMRI experiment. PMID- 26553917 TI - In vivo confocal microscopic corneal images in health and disease with an emphasis on extracting features and visual signatures for corneal diseases: a review study. AB - There is an evolution in the demands of modern ophthalmology from descriptive findings to assessment of cellular-level changes by using in vivo confocal microscopy. Confocal microscopy, by producing greyscale images, enables a microstructural insight into the in vivo cornea in both health and disease, including epithelial changes, stromal degenerative or dystrophic diseases, endothelial pathologies and corneal deposits and infections. Ophthalmologists use acquired confocal corneal images to identify health and disease states and then to diagnose which type of disease is affecting the cornea. This paper presents the main features of the healthy confocal corneal layers and reviews the most common corneal diseases. It identifies the visual signatures of each disease in the affected layer and extracts the main features of this disease in terms of intensity, certain regular shapes with both their size and diffusion, and some specific region of interest. These features will lead towards the development of a complete automatic corneal diagnostic system that predicts abnormalities in the confocal corneal data sets. PMID- 26553918 TI - Correction. PMID- 26553919 TI - Efficacy of conjunctival resection with cyanoacrylate glue application in preventing recurrences of Mooren's ulcer. AB - AIM: To evaluate the role of conjunctival resection along with cyanoacrylate glue and bandage contact lens application in preventing recurrences and arresting progression in cases of Mooren's ulcer. METHOD: This retrospective interventional case series included cases of Mooren's ulcer that underwent conjunctival resection with cyanoacrylate glue and bandage contact lens application between 2011 and 2014. Systemic immunosuppression was initiated depending on the laterality and severity of disease. The primary outcome measures were clinical quiescence and recurrence-free survival. Kaplan-Meier plots were constructed and survival analysis done using the R software environment for statistical analysis. Secondary outcome measures were needed for systemic immunosuppression, change in best-corrected visual acuity and complications encountered. RESULTS: We evaluated 16 eyes of 12 patients who presented to us during the study period. The mean follow-up duration was 9.6 months. All eyes achieved clinical quiescence with a median recurrence-free survival of 141 days. The Kaplan-Meier survival curve showed probability of recurrence-free survival to be 42.5% at 1 year, which further dropped down to 21.3% at 2 years. All patients with recurrence (seven eyes of four patients) required systemic immunosuppression. CONCLUSIONS: Conjunctival resection and cyanoacrylate glue application are not effective in avoiding recurrences and halting the disease progression in cases of Mooren's ulcer. Systemic immunosuppression remains the mainstay of therapy. PMID- 26553920 TI - Correction. PMID- 26553921 TI - Behcet's disease ocular attack score 24 and visual outcome in patients with Behcet's disease. AB - AIMS: To investigate the ability of the Behcet's disease ocular attack score 24 (BOS24) scoring system to predict visual acuity (VA) in patients with ocular Behcet's disease. DESIGN: This is a retrospective study. METHODS: We included 91 eyes of 50 patients with ocular Behcet's disease (33 males, 17 females) who were referred to our hospital between 1986 and 2008 with >5 years follow-up. Total BOS24 scores over a 5-year period, BOS24-5Y, were calculated as the sum of BOS24 scores for each attack over the 5-year study period for each eye. Change in VA was defined as change in best-corrected visual acuity (BCVA) from the first remission to the last remission at the end of the target period. Factors related to change in VA (age, gender, BCVA at the first remission, total number of immunosuppressive medications and total number of ocular attacks during the 5 year period and BOS24-5Y) were evaluated using a linear mixed model. RESULTS: BCVA (logarithm of the minimal angle resolution) deteriorated from 0.16+/-0.30 (mean+/-SD) to 0.21+/-0.37 over the 5-year study period, but there was no statistical difference. The total number of ocular attacks during the 5-year period and BOS24-5Y scores were 10.0+/-7.9 and 36.8+/-40.8, respectively. Linear mixed-model analysis revealed that BOS24-5Y was the most important index for VA deterioration, followed by BCVA at the first remission. CONCLUSIONS: BOS24-5Y was found to be a significant positive prognostic index for VA deterioration in patients with ocular Behcet's disease. PMID- 26553923 TI - Comparison of macular choroidal thicknesses from swept source and spectral domain optical coherence tomography. AB - BACKGROUND: Choroidal thickness (CT) measurements differ between swept source optical coherence tomography (SS-OCT) and spectral domain OCT (SD-OCT) devices for point thickness measurements. We aimed to assess the comparability of mean macular CT measurements between SS-OCT and SD-OCT devices. METHODS: In a prospective cohort study of 25 healthy volunteers, OCT scans were performed sequentially with the deep range imaging (DRI) OCT-1 and Spectralis OCT using standardised imaging protocols. These OCT scans were independently graded by reading centre-certified graders to obtain mean CT in the various Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Paired t tests and intraclass correlation coefficients (ICCs) were used to compare the measurements. RESULTS: The difference in mean central subfield CT between DRI OCT-1 and Spectralis was 49.3 um (p<0.001), while differences in CT in various ETDRS subfields varied from 42.1 to 67.2 um. After manual adjustment of the segmentation boundaries for the central subfield in the DRI OCT-1, the mean central subfield CT for DRI OCT-1 increased from 263.1 to 293.3 um (p<0.001), and the resultant difference between DRI OCT-1 and Spectralis decreased from 49.3 to 19.1 um (a decrease of 61.3%; p<0.001). CT between the three-dimensional and radial scanning protocols of the DRI OCT-1 were highly comparable, with differences generally under 10 um and ICC of 0.888 for the central subfield. CONCLUSIONS: CT measurements between automated segmentations from the DRI OCT-1 and manual segmentations on the Spectralis OCT may differ by more than 50 um. This difference can be reduced, but not eliminated, by manual adjustment of segmentation boundaries by trained graders, and should be accounted for when comparing results between the two devices. PMID- 26553922 TI - Current therapeutic developments in atrophic age-related macular degeneration. AB - Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID- 26553924 TI - Anne Brunet: Gracefully studying how we age. PMID- 26553925 TI - SUMO enters the ring. PMID- 26553926 TI - Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes. AB - The presence of DNA double-strand breaks during mitosis is particularly challenging for the cell, as it produces broken chromosomes lacking a centromere. This situation can cause genomic instability resulting from improper segregation of the broken fragments into daughter cells. We recently uncovered a process by which broken chromosomes are faithfully transmitted via the BubR1-dependent tethering of the two broken chromosome ends. However, the mechanisms underlying BubR1 recruitment and function on broken chromosomes were largely unknown. We show that BubR1 requires interaction with Bub3 to localize on the broken chromosome fragments and to mediate their proper segregation. We also find that Cdc20, a cofactor of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), accumulates on DNA breaks in a BubR1 KEN box-dependent manner. A biosensor for APC/C activity demonstrates a BubR1-dependent local inhibition of APC/C around the segregating broken chromosome. We therefore propose that the Bub3-BubR1 complex on broken DNA inhibits the APC/C locally via the sequestration of Cdc20, thus promoting proper transmission of broken chromosomes. PMID- 26553927 TI - Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes. AB - Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors. PMID- 26553928 TI - Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells. AB - Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 deficiency renders DCs phenotypically mature as they up-regulate the co-stimulatory molecule CD86 from intracellular storages to the cell surface. Cdc42 knockout DCs also accumulate high amounts of invariant chain-major histocompatibility complex (MHC) class II complexes at the cell surface, which cannot efficiently present peptide antigens (Ag's) for priming of Ag-specific CD4 T cells. Proteome analyses showed a significant reduction in lysosomal MHC class II-processing proteins, such as cathepsins, which are lost from DCs by enhanced secretion. As these effects on DCs can be mimicked by chemical actin disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up regulation of intracellular molecules to the cell surface. PMID- 26553929 TI - Cargo-selective apical exocytosis in epithelial cells is conducted by Myo5B, Slp4a, Vamp7, and Syntaxin 3. AB - Mutations in the motor protein Myosin Vb (Myo5B) or the soluble NSF attachment protein receptor Syntaxin 3 (Stx3) disturb epithelial polarity and cause microvillus inclusion disease (MVID), a lethal hereditary enteropathy affecting neonates. To understand the molecular mechanism of Myo5B and Stx3 interplay, we used genome editing to introduce a defined Myo5B patient mutation in a human epithelial cell line. Our results demonstrate a selective role of Myo5B and Stx3 for apical cargo exocytosis in polarized epithelial cells. Apical exocytosis of NHE3, CFTR (cystic fibrosis transmembrane conductance regulator), and GLUT5 required an interaction cascade of Rab11, Myo5B, Slp4a, Munc18-2, and Vamp7 with Stx3, which cooperate in the final steps of this selective apical traffic pathway. The brush border enzymes DPPIV and sucrase-isomaltase still correctly localize at the apical plasma membrane independent of this pathway. Hence, our work demonstrates how Myo5B, Stx3, Slp4a, Vamp7, Munc18-2, and Rab8/11 cooperate during selective apical cargo trafficking and exocytosis in epithelial cells and thereby provides further insight into MVID pathophysiology. PMID- 26553930 TI - Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling. AB - Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation. In this study we report that Notch recycling to the cell surface is dependent on the COMMD-CCDC22-CCDC93 (CCC) complex, a recently identified regulator of endosomal trafficking. Disruption in this system leads to intracellular accumulation of Notch2 and concomitant reduction in Notch signaling. Interestingly, among the 10 copper metabolism MURR1 domain containing (COMMD) family members that can associate with the CCC complex, only COMMD9 and its binding partner, COMMD5, have substantial effects on Notch. Furthermore, Commd9 deletion in mice leads to embryonic lethality and complex cardiovascular alterations that bear hallmarks of Notch deficiency. Altogether, these studies highlight that the CCC complex controls Notch activation by modulating its intracellular trafficking and demonstrate cargo-specific effects for members of the COMMD protein family. PMID- 26553931 TI - AMIGO2, a novel membrane anchor of PDK1, controls cell survival and angiogenesis via Akt activation. AB - The phosphoinositide 3-kinase-Akt signaling pathway is essential to many biological processes, including cell proliferation, survival, metabolism, and angiogenesis, under pathophysiological conditions. Although 3-phosphoinositide dependent kinase 1 (PDK1) is a primary activator of Akt at the plasma membrane, the optimal activation mechanism remains unclear. We report that adhesion molecule with IgG-like domain 2 (AMIGO2) is a novel scaffold protein that regulates PDK1 membrane localization and Akt activation. Loss of AMIGO2 in endothelial cells (ECs) led to apoptosis and inhibition of angiogenesis with Akt inactivation. Amino acid residues 465-474 in AMIGO2 directly bind to the PDK1 pleckstrin homology domain. A synthetic peptide containing the AMIGO2 465-474 residues abrogated the AMIGO2-PDK1 interaction and Akt activation. Moreover, it effectively suppressed pathological angiogenesis in murine tumor and oxygen induced retinopathy models. These results demonstrate that AMIGO2 is an important regulator of the PDK1-Akt pathway in ECs and suggest that interference of the PDK1-AMIGO2 interaction might be a novel pharmaceutical target for designing an Akt pathway inhibitor. PMID- 26553932 TI - The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles. AB - Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation. PMID- 26553934 TI - Diamond: immunohistochemistry versus sequencing in EGFR analysis of lung adenocarcinomas. AB - AIMS: Identification of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKIs). EGFR E746-A750del and L858R mutations are the most common gene alterations, also predicting the best clinical response to TKIs. We evaluated the accuracy of EGFR mutation-specific antibodies in a large cohort of lung adenocarcinomas, with different molecular settings and types of tissue samples. METHODS: 300 lung adenocarcinomas diagnosed on cytology (48 cell blocks), biopsy (157 cases) and surgical resections (95 cases) were selected. All cases were investigated for EGFR by sequencing and two mutation specific antibodies (clone 6B6 for E746-A750del; clone 43B2 for L858R) were tested using an automated immunostainer. Discordant results were investigated by next-generation sequencing (NGS). RESULTS: Overall sensitivity and specificity of mutant-specific antibodies were 58.6% and 98.0%, respectively, and they increased up to 84% and 100% if only tumours harbouring E746-A750del were considered. In 13 discordant cases, NGS confirmed immunohistochemistry results in eight samples. CONCLUSIONS: The EGFR mutation-specific antibodies have a fair/good sensitivity and good/high specificity in identifying classic mutations, but they cannot replace molecular tests. The antibodies work equally well on biopsies and cell blocks, possibly permitting a rapid screening in cases with poor material. PMID- 26553935 TI - Traditional serrated adenoma (TSA): morphological questions, queries and quandaries. AB - AIM: Traditional serrated adenoma (TSA) is an uncommon type of serrated adenoma that can be a precursor to biologically aggressive colorectal cancer that invokes the serrated (accelerated) pathway. The purpose of this review is to address some of the more contentious issues around nomenclature, diagnostic criteria, histological variants, coexistence with other polyp types, the occurrence of dysplasia and the differential diagnosis. RESULTS: While the vast majority of TSAs are exophytic villiform polyps composed of deeply eosinophilic cells, flat top luminal serrations and numerous ectopic crypt foci, histological variants include flat TSA, filiform TSA and one composed of large numbers of mucin containing cells. It is unlikely that there is any biological difference between the histological variants. There is a contention that TSAs are not dysplastic ab initio and that the majority do not show cytological atypia. Two types of dysplasia are associated with TSA. Serrated dysplasia is less well recognised and less commonly encountered than adenomatous dysplasia. TSA with dysplasia must be separated from TSA with coexisting conventional adenoma. CONCLUSIONS: TSA is a characteristic polyp that may be extremely exophytic, flat or composed of mucin rich cells and is typified by numerous ectopic crypt foci. They may coexist with other serrated polyps and conventional adenomas. Approximately 20-25% will be accompanied by adenomatous dysplasia. PMID- 26553933 TI - Protrusive waves guide 3D cell migration along nanofibers. AB - In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions. PMID- 26553937 TI - The N- and C-terminal ends of RPGR can bind to PDE6delta. PMID- 26553936 TI - Chromatin remodeling and bivalent histone modifications in embryonic stem cells. AB - Pluripotent embryonic stem cells (ESCs) are characterized by distinct epigenetic features including a relative enrichment of histone modifications related to active chromatin. Among these is tri-methylation of lysine 4 on histone H3 (H3K4me3). Several thousands of the H3K4me3-enriched promoters in pluripotent cells also contain a repressive histone mark, namely H3K27me3, a situation referred to as "bivalency". While bivalent promoters are not unique to pluripotent cells, they are relatively enriched in these cell types, largely marking developmental and lineage-specific genes which are silent but poised for immediate action. The H3K4me3 and H3K27me3 modifications are catalyzed by lysine methyltransferases which are usually found within, although not entirely limited to, the Trithorax group (TrxG) and Polycomb group (PcG) protein complexes, respectively, but these do not provide selective bivalent specificity. Recent studies highlight the family of ATP-dependent chromatin remodeling proteins as regulators of bivalent domains. Here, we discuss bivalency in general, describe the machineries that catalyze bivalent chromatin domains, and portray the emerging connection between bivalency and the action of different families of chromatin remodelers, namely INO80, esBAF, and NuRD, in pluripotent cells. We posit that chromatin remodeling proteins may enable "bivalent specificity", often selectively acting on, or selectively depleted from, bivalent domains. PMID- 26553938 TI - PDE6D binds to the C-terminus of RPGR in a prenylation-dependent manner. PMID- 26553939 TI - The radical openness of science and innovation: Why uncertainty is inherent in the openness towards the future. PMID- 26553940 TI - Essentially deadly: living with toxic elements: Humans and plants have evolved various mechanisms to deal with and even adopt toxic heavy metals. PMID- 26553941 TI - Shortage of neurologists in the Brazilian Amazon. PMID- 26553942 TI - Ultra-acute CT perfusion imaging: A stroke in the scanner. PMID- 26553943 TI - The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail? PMID- 26553944 TI - The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail? PMID- 26553945 TI - Role for the microtubule-associated protein tau variant p.A152T in risk of alpha synucleinopathies. PMID- 26553946 TI - Teaching NeuroImages: Recurrent SSPE presenting as Anton syndrome with cortical ribboning. PMID- 26553947 TI - Teaching Video NeuroImages: Feeding dystonia in chorea-acanthocytosis. PMID- 26553949 TI - Automated glycan assembly of xyloglucan oligosaccharides. AB - We report the automated glycan assembly of oligosaccharide fragments related to the hemicellulose xyloglucan (XG). Iterative addition of monosaccharide and disaccharide building blocks to a solid support provided seven cellulose and xyloglucan fragments including XXGG- and XXXG-type oligosaccharides. PMID- 26553948 TI - Associations Between Anxiety Sensitivity, Negative Affect, and Smoking During a Self-Guided Smoking Cessation Attempt. AB - INTRODUCTION: Anxiety sensitivity (AS), defined as the extent to which individuals believe anxiety and internal sensations have harmful consequences, is associated with the maintenance and relapse of smoking. Yet, little is known about how AS interplays with negative affect during the quit process in terms of smoking behavior. To address this gap, the current study examined the dynamic interplay between AS, negative affect, and smoking lapse behavior during the course of a self-guided (unaided) quit attempt. METHODS: Fifty-four participants (33.3% female; M age = 34.6, SD = 13.8) completed ecological momentary assessment procedures, reporting on negative affect and smoking status via a handheld computer device, three times per day for the initial 14 days of the self-guided cessation attempt. RESULTS: As expected, a significant interaction was observed, such that participants characterized by high levels of AS were at a higher risk of smoking on days when negative affect was high (relative to low). Results also revealed a significant interaction between AS and daily smoking lapse behavior in terms of daily change in negative affect. Participants characterized by high levels of AS reported significant increases in same-day negative affect on days when they endorsed smoking relative to days they endorsed abstinence. CONCLUSIONS: This study provides novel information about the nature of AS, negative affect, and smoking behavior during a quit attempt. Results suggest there is a need for specialized intervention strategies to enhance smoking outcome among this high-risk group that will meet their unique "affective needs." IMPLICATIONS: The current study underscores the importance of developing specialized smoking cessation interventions for smokers with emotional vulnerabilities. PMID- 26553950 TI - Unplanned reoperations after vascular surgery. AB - OBJECTIVE: Existing literature on unplanned reoperation (UR) after vascular surgery is limited. The frequency of 30-day UR and its association with other adverse outcomes was analyzed. METHODS: Patients who underwent vascular procedures in the American College of Surgeons National Surgical Quality Improvement Program (2012) were abstracted. UR, captured by a distinct variable now available in the data set, and its association with complications, readmissions, mortality, and failure to rescue (FTR) were analyzed using bivariate and multivariate methods. RESULTS: Among 35,106 patients, 3545 URs were performed on 2874 patients. The overall UR rate was 10.1%. Among patients who underwent URs, approximately 80.4%, 15.8%, and 3.8% had one, two, and three or more reoperations, respectively; 39.4% of URs occurred after initial discharge. Median time to UR was 7 days but varied by procedure. Procedures with the highest UR rates were embolectomy (18.2%), abdominal bypass (14.4%), and open procedures for peripheral vascular disease (13.8%). Common indications for UR were hemorrhage, graft failure or infection, thromboembolic events, and wound complications. Patients with URs had higher rates of subsequent complications (49.9% vs 19.9%; P < .001), readmission (41.8% vs 7.0%; P < .001), and mortality (8.0% vs 2.5%; P < .001) than those not undergoing URs. FTR was more likely among patients who had a UR (13.6% vs 9.3%; P < .001); this varied within procedure groups. After multivariate adjustment, UR was independently associated with mortality in an incremental fashion (for one UR: adjusted odds ratio, 2.0; 95% confidence interval, 1.7-2.5; for two or more URs: adjusted odds ratio, 3.1; 95% confidence interval, 2.2-4.2). CONCLUSIONS: URs within 30 days are frequent among patients undergoing vascular surgery and are associated with worse outcomes, including mortality and FTR. PMID- 26553951 TI - Life expectancy and causes of death after repair of intact and ruptured abdominal aortic aneurysms. AB - BACKGROUND: Life expectancy and causes of death after abdominal aortic aneurysm (AAA) repair are not well characterized. Population aging and improved secondary prevention may have modified the prognosis of these patients. We designed a retrospective cohort study to determine the vital prognosis, causes of death, and differences in outcome after intact and ruptured AAA. METHODS: All patients with AAA treated from 2003 to 2011 at a single university institution in The Netherlands were analyzed. Survival status was derived from civil registry data. Causes of death were obtained from death certificates. The primary end point was overall mortality. Secondary end points were cardiovascular, cancer-related, and AAA-related mortality. Predictors for perioperative and late survival were obtained by logistic regression and Cox regression models, respectively. RESULTS: The study included 619 consecutive AAA patients (12% women; mean age, 72 years), of whom 152 (24.5%) had ruptured AAAs. Endovascular repair was performed in 390 (63%). Rupture (odds ratio [OR], 10.63; 95% confidence interval [CI], 4.80-23.5), open repair (OR, 3.59; 95% CI, 1.69-7.62), renal insufficiency (OR, 2.94; 95% CI, 1.51-3.46), and age (OR, 1.08 per year; 95% CI, 1.09-1.15) were predictors of 30 day mortality. Five-year survival expectancy was 65% for intact AAA and 41% for ruptured AAA (P < .001). Cardiovascular deaths unrelated to the AAA occurred in 35% and cancer-related deaths in 29% of deceased patients. Predictors for late mortality were history of prior malignant disease (hazard ratio, 2.83; 95% CI, 1.99-4.03) and age (hazard ratio, 1.08 per year; 95% CI, 1.05-1.10). After 30 days, only six deaths (1.1%) were AAA related. CONCLUSIONS: Endovascular repair reduced perioperative mortality by threefold, but no survival benefit was observed at long term. After the perioperative period, survival of ruptured AAA and intact AAA patients was not different. Deaths were distributed in similar proportions between cardiovascular and cancer-related causes. PMID- 26553952 TI - Abdominal aortic aneurysm anatomic severity grading score predicts implant related complications, systemic complications, and mortality. AB - OBJECTIVE: The aim of our study was to examine the predictive value of the anatomic severity grading (ASG) score for abdominal aortic aneurysms (AAAs) on implant-related complications, systemic complications, and mortality at 30-day and midterm, defined as 2 years, follow-up assessments. METHODS: Patients who underwent endovascular aneurysm repair for infrarenal AAAs between 2009 and 2012 were retrospectively reviewed, and ASG scores were calculated from three dimensonal computed tomography reconstructions. Two independent patient groups were created: those with a low ASG score (score <14) and those with a high ASG score (score >=14). RESULTS: We identified 190 patients (77% male), with a mean age of 73 years, and 84% Caucasian, with 104 patients in the low-score group and 86 in the high-score group. Within 30 days of the index endovascular aneurysm repair, 10 implant-related complications occurred in six patients (3%) and 25 systemic complications in 18 (9%). The incidence of 30-day implant-related complications was not significantly different between the low-score group (2 [2%]) and the high-score group (4 [5%]; P = .41). The incidence of patients with 30-day systemic complications was significantly different between the low-score group (5 [5%]) and the high score group (13 [15%]; P = .023). A composite end point of combined implant-related and systemic complications at 30 days showed there was a statistically significant difference between the low-score (7 [7%]) and high-score group (17 [20%]; P = .007). At a midterm follow up of 26 months (range, 1-64 months), implant-related complications occurred in 21 patients (11%), and systemic complications occurred in 29 (15%). The incidence of implant related complications was significantly different between the low-score group (7 [7%]) and the high-score group (14 [16%]; P = .037). The incidence of midterm systemic complications was significantly different between the low-score group (11 [11%]) and the high-score group (18 [21%]; P = .048). A composite end point of combined implant-related and systemic complications at midterm follow-up resulted in a statistically significant difference between the low-score group (16 [15%]) and the high-score group (26 [30%]; P = .014). Kaplan-Meier analysis revealed that the low-score group had fewer overall complications (combined implant-related and systemic) at 1 year (14% vs 34%) and 2 years (15% vs 45%) compared with the high-score group (P < .001). The low-scoring group also had significantly higher survival at 1 year (96% vs 86%) and 2 years (88% vs 84%) compared with the high-score group (P = .047). CONCLUSIONS: The AAA ASG score can be used to predict patients at risk for midterm implant-related complications, 30 day and midterm systemic complications, and all-cause mortality. PMID- 26553953 TI - The effect of anesthesia type on major lower extremity amputation in functionally impaired elderly patients. AB - OBJECTIVE: Patients undergoing major lower extremity amputations are at risk for a wide variety of perioperative complications. Elderly patients with any functional impairment have been shown to be at high risk for these adverse events. Our goal was to determine the association between the type of anesthesia general anesthesia (GA) and regional/spinal anesthesia (RA)-on perioperative outcomes after lower extremity amputation in these elderly and functionally impaired patients. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data set (2005-2012) was queried to identify all patients aged >=75 years with partial or total functional impairment who underwent major lower extremity amputations. Propensity matching and multivariate analysis were performed to isolate the effect of anesthesia type. RESULTS: We identified 3260 patients (50% male), 2558 GA patients and 702 RA patients, who were a mean age of 82 years. Anatomic distribution was 59% above the-knee and 41% below-the-knee amputations. Patients undergoing GA were more likely to have impaired sensorium (9% vs 6%; P = .035), be on anticoagulation or have a bleeding disorder (33% vs 17%; P < .001), have had a previous operation <=30 days (16% vs 10%; P < .001), and be operated on by a nonvascular surgeon (16% vs 12%; P = .033). GA was associated with shorter anesthesia time to surgery (36 +/- 48 vs 42 +/- 49 minutes; P < .001) but a similar operative time (66 +/- 33 vs 64 +/- 33 minutes; P = .292) compared with RA. After propensity matching, rates of 30-day mortality (14% vs 12%; P = .135), postoperative myocardial infarction/cardiac arrest (2.9% vs 3.1%; P = .756), pulmonary complications (7.3% vs 6.7%; P = .632), stroke (0.7% vs 0.9%; P = .694), urinary tract infections (6.7% vs 6.5%; P = .887), and wound complications (7.6% vs 7.6%; P = .999) were similar in patients undergoing GA and RA, respectively. Median length of stay was similar in both groups (5 vs 5.5 days; P = .309). Multivariable analyses confirmed that anesthesia type did not significantly affect morbidity and mortality. CONCLUSIONS: The mode of anesthesia, GA vs RA, did not have significant effect on perioperative outcomes after major lower extremity amputation in the functionally impaired geriatric population. These findings provide an evidence base that will allow surgeons, anesthesiologists, and patients to make an informed decision about anesthesia type for their procedure. PMID- 26553954 TI - Polyurethane dressing, tetracycline and salicylic acid use for treatment of digital dermatitis in cattle. A comparative study. AB - OBJECTIVE: The use of antibiotics is a proven approach for local and systemic treatment of digital dermatitis (DD). Even if they are administered only locally and at low dosage, their use should be restricted to an absolute minimum. The efficacy of a commercial polyurethane wound dressing in treating acute digital dermatitis was compared with topical treatment using a commercially available tetracycline spray and a salicylic acid paste. MATERIALS AND METHODS: A total of 105 cows in a dairy farm (with about 160 dairy cows) were included in the study, with 101 cows needing topical treatment for digital dermatitis on one or both hind feet. All animals underwent hoof trimming prior to the treatment. Affected feet (n = 152) were randomly assigned to one of three comparable treatment groups. Topical treatment was administered to all visible digital dermatitis lesions. Animals in the positive control groups were given a topical treatment of tetracycline (53 DD lesions in 49 cows) or salicylic acid (53 DD lesions in 50 cows) formulations, whose therapeutic effects were scientifically verified. Spray was applied once, at a usual dosage and without any bandage. Salicylic acid paste was fixed in place with a bandage for 5 days. In the test group (46 DD lesions in 45 cows), a polyurethane bandage was left in place for 10 days. Whereas, 47 feet (from 38 cows) without lesions or with lesions showing no pain were designated as group 0. Each lesion was evaluated at day 0 during trimming, and on day 10 and 36. The lesions were scored based on severity and size. RESULTS: All groups showed a statistically significant improvement in the clinical appearance of the lesions at day 10. There were no significant differences in the findings between the second and the third evaluation (day 10 and day 36) either within a group or between the groups. CONCLUSION: The use of an alternative treatment regimen like a polyurethane wound dressing shows good clinical healing, it is as effective as the conventional methods, and unlike the conventional methods, does not require a latency period. PMID- 26553955 TI - Insight into the retention processes of phthalate metabolites on different liquid chromatography stationary phases for the development of improved separation methods. AB - The retention behavior of nine MPAEs has been studied, using commercial LC columns with octadecylsilane (ODS), phenyl, and amide-type SPs. First, it was found that the use of methanol in the mobile phase is not advisable, because induce a transesterification reaction of MPAEs in the electrospray ion source, regardless of the SP used. On the other hand, different responses were observed when representing the logarithm of retention factors (k) vs. the volume fraction of ACN (phi) in the mobile phase, for the three SPs tested. A quite linear trend was obtained for ODS (at phi values below 0.80) and Phenyl columns. On the contrary, the Amide column shows a striking U-shape trend, typical of both hydrophobic and hydrophilic retention mechanisms. Therefore, the separation process was mainly hydrophobic in the ODS and phenyl SPs, but in the amide-type a dual retention mechanism was found, showing zones with predominant hydrophobic or hydrophilic interactions, depending on both the compound and the experimental conditions. A high content of acetonitrile (>75%) and low concentration of formic acid in the mobile phase promote the hydrophilic separation mechanism for MPAEs on the amide SP. So, this dual separation mechanism can be modulated modifying the pH and content of organic modifier in the mobile phase, allowing greater flexibility to develop improved methods. Taking advantage of this, a separation method was optimized in this amide column using a Box-Wilson Central Composite experimental design, which allows separating the studied MPAEs with a time-saving of around 40% comparing to the conventional phenyl SP. PMID- 26553956 TI - Method developments approaches in supercritical fluid chromatography applied to the analysis of cosmetics. AB - Analyses of complex samples of cosmetics, such as creams or lotions, are generally achieved by HPLC. These analyses are often multistep gradients, due to the presence of compounds with a large range of polarity. For instance, the bioactive compounds may be polar, while the matrix contains lipid components that are rather non-polar, thus cosmetic formulations are usually oil-water emulsions. Supercritical fluid chromatography (SFC) uses mobile phases composed of carbon dioxide and organic co-solvents, allowing for good solubility of both the active compounds and the matrix excipients. Moreover, the classical and well-known properties of these mobile phases yield fast analyses and ensure rapid method development. However, due to the large number of stationary phases available for SFC and to the varied additional parameters acting both on retention and separation factors (co-solvent nature and percentage, temperature, backpressure, flow rate, column dimensions and particle size), a simplified approach can be followed to ensure a fast method development. First, suited stationary phases should be carefully selected for an initial screening, and then the other operating parameters can be limited to the co-solvent nature and percentage, maintaining the oven temperature and back-pressure constant. To describe simple method development guidelines in SFC, three sample applications are discussed in this paper: UV-filters (sunscreens) in sunscreen cream, glyceryl caprylate in eye liner and caffeine in eye serum. Firstly, five stationary phases (ACQUITY UPC(2)) are screened with isocratic elution conditions (10% methanol in carbon dioxide). Complementary of the stationary phases is assessed based on our spider diagram classification which compares a large number of stationary phases based on five molecular interactions. Secondly, the one or two best stationary phases are retained for further optimization of mobile phase composition, with isocratic elution conditions or, when necessary, two-step gradient elution. The developed methods were then applied to real cosmetic samples to assess the method specificity, with regards to matrix interferences, and calibration curves were plotted to evaluate quantification. Besides, depending on the matrix and on the studied compounds, the importance of the detector type, UV or ELSD (evaporative light-scattering detection), and of the particle size of the stationary phase is discussed. PMID- 26553957 TI - Suspect screening of emerging pollutants and their major transformation products in wastewaters treated with fungi by liquid chromatography coupled to a high resolution mass spectrometry. AB - A new approach for the screening of 33 pharmaceuticals and 113 of their known transformation products in wastewaters was developed. The methodology is based on the analysis of samples by liquid chromatography coupled to high resolution mass spectrometry (HRMS) followed by data processing using specific software and manual confirmation. A home-made library was built with the transformation products reported in literature for the target pharmaceuticals after treatment with various fungi. The method was applied to the search of these contaminants in 67 samples generated along treatment of wastewaters with white-rot fungus Trametes versicolor. The screening methodology allowed the detection of different transformation products (TPs) generated from degradation of parent compounds after fungal treatment. This approach can be a useful tool for the rapid screening and tentative detection of emerging contaminants during water treatment in both full and batch-scale studies when pure standards are not available. PMID- 26553958 TI - Resource implications of risk-reducing mastectomy and reconstruction. AB - AIM: Risk-reducing mastectomy (RRM) is on the increase, now frequently combined with breast reconstruction (BR). However, the resource implications associated with bilateral mastectomy and reconstruction are unknown. This study assessed the overall cost of performing risk-reducing surgery. METHODS: All cases of RRM and BR performed between 1991 and 2011 at this hospital were identified from a prospectively collected database. All patients undergoing bilateral mastectomy were included, when at least one mastectomy was risk-reducing. Overall treatment costs for all surgical procedures, complications, revisional procedures and outpatient attendances were calculated and compared to the National Tariff allowed. Mann-Whitney U and Fischer's exact tests were used to calculate levels of significance. RESULTS: Fifty patients underwent bilateral mastectomy and BR (median follow up 20 [range 1-106] months), 72 were Latissimus Dorsi reconstructions (LDR) and 28 were Subpectoral reconstructions (SPR). LDR took longer than SPR (p = 0.001), with a greater length of stay (p = 0.024). Nine percent of patients returned to theatre for early complications, but the type of BR did not influence the early complication rate (LDR versus SPR, p = 0.345) or the need for additional unplanned procedures (LDR versus SPR, p = 0.671). The overall mean cost for bilateral RRM and BR was L14,797 per patient. The inpatient cost for bilateral RRM and LDR was L10,082 compared with L5,905 SPR. Both procedures exceeded the L5,697 tariff allowed in the UK. CONCLUSION: Bilateral RRM and BR is a safe procedure, but the resource implications are considerable and exceed the tariff allowed, particularly when performing more complex techniques. PMID- 26553959 TI - Energy balance in transition cows and its association with health, reproduction and milk production. AB - OBJECTIVE: It was the purpose of this study to determine the effects of non esterified fatty acids (NEFA) concentrations at different time periods of the transition period as well as lactation number on metabolism, health, reproduction and milk production in dairy cows. MATERIAL AND METHODS: This trial was conducted in a single dairy herd located in Northern Germany. Of the herd, which comprised 330 lactating Holstein cows housed in a free stall barn and fed a total mixed ration (TMR), 83 primiparous and multiparous cows were randomly selected. Animals were checked for body condition score (BCS), locomotion score, calving data, quality of colostrum, reproductive measures, daily rectal temperature of the first 10 days post-partum (p. p.), health data and culling rates up to 200 days in milk (DIM) as well as milk production until 305 DIM. Three different time periods were considered: 3 and 1 week ante partum (a. p.); partus and 1 week p. p.; 3 weeks p. p. RESULTS: Animals with NEFA concentrations >= 0.4 mmol/l ante partum had a higher risk of no ovarian activity in week 5 p. p. and of subclinical ketosis post partum than cows with lower NEFA concentrations (p < 0.05). Cows with NEFA concentrations >= 1.1 mmol/l in week 1 p. p., in comparison to those with lower NEFA concentrations, showed a higher prevalence of clinical ketosis (24.1% vs. 5.9%), subclinical ketosis (62.1% vs. 34.0%) and culling rate within 200 DIM (34.5% vs. 14.0%) (p < 0.05). Cows with NEFA concentrations >= 0.3 mmol/l at week 3 p. p. had higher 100- and 305-day milk yields than cows with lower NEFA concentrations (p < 0.05). First lactating heifers were at higher risk to loose body condition ante partum, of dystocia, fever within the first 10 DIM, metritis, clinical and subclinical ketosis as well as to develop a disease within the first 30 DIM (p < 0.05). Multipara were more likely to loose body condition after calving, to a prolonged calving to first service interval and to higher milk yields (p < 0.05). CONCLUSION: In conclusion increased NEFA concentrations during the transition period as well as parity can have an influence on health, production and reproduction of dairy cows. PMID- 26553960 TI - Intraoperative Corticosteroid Injection at the Time of Knee Arthroscopy Is Associated With Increased Postoperative Infection Rates in a Large Medicare Population. AB - PURPOSE: To employ a national database of Medicare patients to evaluate the association of ipsilateral intra-articular knee corticosteroid injections at the time of knee arthroscopy with the incidence of postoperative infection. METHODS: A national Medicare insurance database was queried for patients who underwent ipsilateral intra-articular corticosteroid injection of the knee at the time of knee arthroscopy from 2005 to 2012. Patients who underwent arthroscopically assisted open procedures, those who underwent more complex arthroscopic procedures, and those for whom laterality were not coded were excluded. This study group was compared to a control cohort of patients without intraoperative steroid injections that was matched to the study group for age, gender, obesity, diabetes mellitus, and smoking status. Infection rates within 3 and 6 months postoperatively were assessed using International Classification of Diseases, 9th Revision, and Current Procedural Terminology codes. RESULTS: The incidence of postoperative infection rates after knee arthroscopy was significantly higher at 3 months (0.66%; odds ratio [OR], 2.6; P < .0001) and 6 months (1.92%; OR, 3.6; P < .0001) in patients who underwent ipsilateral intra-articular knee steroid injection at the time of knee arthroscopy (n = 2,866) compared with matched controls without intraoperative injections (n = 170,350) at 3 months (0.25%) and 6 months (0.54%). CONCLUSIONS: The present study demonstrates a significant increase in postoperative infection in Medicare patients who underwent ipsilateral intra-articular knee corticosteroid injections at the time of knee arthroscopy compared with a matched control group without intraoperative injection. LEVEL OF EVIDENCE: Therapeutic Level III, retrospective comparative study. PMID- 26553961 TI - Current Practice for the Surgical Treatment of SLAP Lesions: A Systematic Review. AB - PURPOSE: To analyze current literature reporting surgical treatment of SLAP lesions to examine the consistency of reported surgical details (surgical indications, surgical technique, and postoperative rehabilitation) that are deemed important for best treatment outcomes and to try to establish a consensus regarding treatment. METHODS: A systematic review of papers reporting surgical treatment of a SLAP lesion was performed. Each paper was analyzed for the description of (1) the arthroscopic indications for surgery; (2) surgical aspects including type, location, and number of anchors and sutures; (3) description of criteria for determination of completeness of the repair; and (4) postoperative rehabilitation details. These findings were also analyzed to determine whether a consensus could be developed regarding surgical treatment. RESULTS: Twenty-six papers were included, with 12 focused on isolated SLAP repair and 14 focused on combined SLAP repair with other lesions; 54% did not report indications for surgery. Reporting of the anchor/suture details was not consistent, with 35% reporting some variation of 12:00 placement but 31% not reporting the position of placement; 89% of papers did not report the criteria for determining completeness of the repair; 85% reported general postoperative rehabilitation guidelines, but only 4% reported in-depth details. CONCLUSIONS: This review demonstrated a wide variability in the reported surgical aspects and that a relatively high percentage of papers did not report many of the details. This lack of precision and consistency makes analysis of individual papers and comparison between papers and their outcomes difficult and does not allow a consensus regarding current practice to be developed. These findings may be some of the factors responsible for the variability in treatment outcomes and suggest that efforts could be directed toward consistency in documenting and reporting surgical indications, surgical techniques, surgical endpoints, and efficacious rehabilitation programs. LEVEL OF EVIDENCE: Level IV, systematic review of level III-IV studies. PMID- 26553962 TI - The Role of Hip Arthroscopy in Investigating and Managing the Painful Hip Resurfacing Arthroplasty. AB - PURPOSE: To determine the safety and efficacy of hip arthroscopy performed in the peripheral compartment as a diagnostic and therapeutic treatment option for patients with hip pain after hip resurfacing surgery. METHODS: Indications for hip arthroscopy after hip resurfacing included patients with a symptomatic hip resurfaced arthroplasties who did not respond to nonoperative treatment. Patients who underwent a hip arthroscopy after a painful hip resurfacing were included with a minimum of 1 year follow-up. Subgroup analysis was performed according to whether an established diagnosis was made before arthroscopic intervention or not. Subjective measures were based on Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, and results were calculated and analyzed. RESULTS: We included 68 patients (26 male [38%] and 42 female [62%]) who underwent subsequent hip arthroscopy from a population of 978 consecutive hip resurfaced arthroplasties performed between 1999 and 2010. The average age was 58 (range, 37 to 78 years). The mean follow-up after hip arthroscopy was 3.4 years (range, 12 months to 5.8 years). Patients who had an established diagnosis (n = 41) before hip arthroscopy showed statistical improvement in their WOMAC scores (7 to 2, P < .001). Only 3 (7%) of these 41 patients failed and were converted to a total hip replacement (THR); however, patients who did not have an established diagnosis (n = 27) before undergoing hip arthroscopy showed statistical worsening of the WOMAC (15 to 21, P = .002). Ten (37%) of these 27 patients without a diagnosis failed and needed to be converted to a THR. A significant correlation was found between the collections found on ultrasound (psoas bursa and/or in the hip joint) and the need for synovectomy (P = .01). The overall revision rate to THR after hip resurfacing in our group of patients was 1.3% (n = 13). Female patients were more likely to require postresurfacing hip arthroscopy with 42 (60%) female to only 26 (40%) male patients undergoing this procedure. In our study population, 70% (14/21, P < .05) of patients with hip pain caused by severe metal synovial reaction or metal-on-metal reaction were women. A total of 5 (7%) patients had minor-to-mild complications after hip arthroscopy. CONCLUSIONS: Hip arthroscopy is a safe surgical treatment option for those patients with a painful hip resurfacing arthroplasty. Having an accurate diagnosis before hip arthroscopy improves the likelihood a good outcome. LEVEL OF EVIDENCE: Level IV - therapeutic case series. PMID- 26553963 TI - Influence of the intervention of exercise on obese type II diabetes mellitus: A meta-analysis. AB - AIM: The study aimed to assess the effect of exercise intervention on the management of obese T2DM patients. METHODS: The literature retrieval was conducted in relevant databases from their inception to 2015, with predefined searching strategy and selection criteria. The Cochrane Collaboration's tool was utilized to assess the quality of included studies. Weighted mean difference (WMD) with its corresponding 95% CI (confidence interval) was used as the effect size. RESULTS: A subset of 13 eligible studies was selected. Exercise significantly reduced the concentration of high sensitivity C reactive protein (4 months: WMD=-1.03, 95% CI: -1.77 to -0.29, P<0.01), triglyceride (6 months: WMD= 24.75, 95% CI: -27.67 to -21.83, P<0.01), diastolic blood pressure (6 months: WMD=-2.70, 95% CI: -4.12 to -1.28, P=0.0002), systolic blood pressure (WMD=-7.98, 95% CI: -9.87 to -6.08, P<0.01)), HbA1c (4 months: WMD=-0.25, 95% CI: -0.49 to 0.02, P=0.04) and homeostasis model assessment-insulin resistance (3 months: WMD= 0.19, 95% CI: -0.37 to -0.01, P=0.04); and a pronounced increase of HDL-C (12 months: WMD=3.57, 95% CI: 1.92 to 5.21, P<0.01). CONCLUSION: Exercise was beneficial to obese T2DM patients. PMID- 26553964 TI - Endoscopic sinus surgery dissection courses using a real simulator: the benefits of this training. AB - INTRODUCTION: Endonasal surgeries are among the most common procedures performed in otolaryngology. Due to difficulty in cadaver acquisition and the intrinsic risks of training residents during operations on real patients, nasosinusal endoscopic dissection courses utilizing real simulators, such as the Sinus Model Otorhino Neuro Trainer are being developed as a new technique to facilitate the acquisition of better anatomical knowledge and surgical skill. OBJECTIVE: To evaluate the efficacy of nasosinusal endoscopic dissection courses with the Sinus Model Otorhino Neuro Trainer simulator in the training of otolaryngology surgeons. METHODS: A prospective, longitudinal cohort study was conducted with 111 otolaryngologists who participated in a theoretical and practical course of endoscopic surgery dissection using the Sinus Model Otorhino Neuro Trainer simulator, with application of questionnaires during and after the course. RESULTS: From the ten procedures performed utilizing the simulator, the evaluation revealed mean scores from 3.1 to 4.1 (maximum of 5). Seventy-seven participants answered the questionnaire six months after the end of the course. 93% of them reported that they could perform the procedures more safely following the course, 98% reported an improvement in their anatomical and clinical knowledge, and 85% related an improvement in their surgical ability. After the course, the number of endoscopic surgeries increased in 40% of the respondents. CONCLUSION: Endoscopic sinus dissection courses using the Sinus Model Otorhino Neuro Trainer simulator proved to be useful in the training of otolaryngologists. PMID- 26553965 TI - The effect of statins on chronic obstructive pulmonary disease exacerbation and mortality: a systematic review and meta-analysis of observational research. AB - The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes. We conducted a systematic review and meta analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events. Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions. The hazard ratio (HR) with 95% confidence interval (CI) was estimated. Fifteen studies with a total of 238,459 patients were included. Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73). Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72). Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75). Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke. Our systematic review showed a clear benefit of statins in patients with COPD. PMID- 26553966 TI - A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty. AB - Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1alpha/beta will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL 1alpha/beta induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1alpha/beta treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1alpha/beta availability and not their ability to respond to it. PMID- 26553967 TI - Fibrosis is a common outcome following total knee arthroplasty. AB - Total knee arthroplasty (TKA) is one of the most successful orthopaedic procedures that alleviates pain and restores function in patients with degenerative knee joint diseases. Arthrofibrosis, abnormal scarring in which dense fibrous tissue prevents normal range of motion, develops in ~3-10% of TKA patients. No prophylactic intervention is available and treatment is restricted to aggressive physiotherapy or revision surgery. Tissue was collected from patients undergoing primary (n = 30) or revision (n = 27) TKA. Revision patients were stratified as non-arthrofibrotic and arthrofibrotic. Tissue was macroscopically and histologically compared to improve our understanding of the pathophysiology of arthrofibrosis. Macroscopically, tissue from primary TKA presents as homogenous, fatty tissue whereas tissue from revision TKA presents as dense, pigmented tissue. Histologically, there was dramatic tissue remodelling, increased collagen deposition and increased (myo)fibroblast staining in tissue from revision TKA. Significantly, tissue architecture was similar between revision patients regardless of clinically diagnosis. There are significant differences in architecture and composition of tissue from revision TKA over primary TKA. Surprisingly, whether revision TKA were clinically diagnosed as arthrofibrotic or non-arthrofibrotic there were still significant differences in fibrotic markers compared to primary TKA suggesting an ongoing fibrotic process in all revision knees. PMID- 26553969 TI - Endurance training and maximal oxygen consumption with ageing: Role of maximal cardiac output and oxygen extraction. AB - BACKGROUND: The increase in maximal oxygen consumption (VO2max) with endurance training is associated with that of maximal cardiac output (Qmax), but not oxygen extraction, in young individuals. Whether such a relationship is altered with ageing remains unclear. Therefore, we sought systematically to review and determine the effect of endurance training on and the associations among VO2max, Qmax and arteriovenous oxygen difference at maximal exercise (Ca-vO2max) in healthy aged individuals. DESIGN AND METHODS: We conducted a systematic search of MEDLINE, Scopus and Web of Science, from their inceptions until May 2015 for articles assessing the effect of endurance training lasting 3 weeks or longer on VO2max and Qmax and/or Ca-vO2max in healthy middle-aged and/or older individuals (mean age >=40 years). Meta-analyses were performed to determine the standardised mean difference (SMD) in VO2max, Qmax and Ca-vO2max between post and pre-training measurements. Subgroup and meta-regression analyses were used to evaluate the associations among SMDs and potential moderating factors. RESULTS: Sixteen studies were included after systematic review, comprising a total of 153 primarily untrained healthy middle-aged and older subjects (mean age 42-71 years). Endurance training programmes ranged from 8 to 52 weeks of duration. After data pooling, VO2max (SMD 0.89; P < 0.0001) and Qmax (SMD 0.61; P < 0.0001) were increased after endurance training; no heterogeneity among studies was detected. Ca-vO2max was only increased with endurance training interventions lasting more than 12 weeks (SMD 0.62; P = 0.001). In meta-regression, the SMD in Qmax was positively associated with the SMD in VO2max (B = 0.79, P = 0.04). The SMD in Ca-vO2max was not associated with the SMD in VO2max (B = 0.09, P = 0.84). CONCLUSIONS: The improvement in VO2max following endurance training is a linear function of Qmax, but not Ca-vO2max, through healthy ageing. PMID- 26553970 TI - Aligned carbon nanotube array stiffness from stochastic three-dimensional morphology. AB - The landmark theoretical properties of low dimensional materials have driven more than a decade of research on carbon nanotubes (CNTs) and related nanostructures. While studies on isolated CNTs report behavior that aligns closely with theoretical predictions, studies on cm-scale aligned CNT arrays (>10(10) CNTs) oftentimes report properties that are orders of magnitude below those predicted by theory. Using simulated arrays comprised of up to 10(5) CNTs with realistic stochastic morphologies, we show that the CNT waviness, quantified via the waviness ratio (w), is responsible for more than three orders of magnitude reduction in the effective CNT stiffness. Also, by including information on the volume fraction scaling of the CNT waviness, the simulation shows that the observed non-linear enhancement of the array stiffness as a function of the CNT close packing originates from the shear and torsion deformation mechanisms that are governed by the low shear modulus (~1 GPa) of the CNTs. PMID- 26553968 TI - Dihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function. AB - Post-transcriptional regulation is an essential determinant of gene expression programs in physiological and pathological conditions. HuR is a RNA-binding protein that orchestrates the stabilization and translation of mRNAs, critical in inflammation and tumor progression, including tumor necrosis factor-alpha (TNF). We identified the low molecular weight compound 15,16-dihydrotanshinone-I (DHTS), well known in traditional Chinese medicine practice, through a validated high throughput screening on a set of anti-inflammatory agents for its ability to prevent HuR:RNA complex formation. We found that DHTS interferes with the association step between HuR and the RNA with an equilibrium dissociation constant in the nanomolar range in vitro (Ki = 3.74 +/- 1.63 nM). In breast cancer cell lines, short term exposure to DHTS influences mRNA stability and translational efficiency of TNF in a HuR-dependent manner and also other functional readouts of its post-transcriptional control, such as the stability of selected pre-mRNAs. Importantly, we show that migration and sensitivity of breast cancer cells to DHTS are modulated by HuR expression, indicating that HuR is among the preferential intracellular targets of DHTS. Here, we disclose a previously unrecognized molecular mechanism exerted by DHTS, opening new perspectives to therapeutically target the HuR mediated, post-transcriptional control in inflammation and cancer cells. PMID- 26553971 TI - [The Spanish Academy of Dermatology and Venereology App: The New Digital Era]. PMID- 26553972 TI - Baseline social amotivation predicts 1-year functioning in UHR subjects: A validation and prospective investigation. AB - Social amotivation and diminished expression have been reported to underlie negative symptomatology in schizophrenia. In the current study we sought to establish and validate these negative symptom domains in a large cohort of schizophrenia subjects (n=887) and individuals who are deemed to be Ultra-High Risk (UHR) for psychosis. Confirmatory factor analysis conducted on PANSS item domains demonstrate that the dual negative symptom domains exist in schizophrenia and UHR subjects. We further sought to examine if these negative symptom domains were associated with functioning in UHR subjects. Linear regression analyses confirmed that social amotivation predicted functioning in UHR subjects prospectively at 1 year follow up. Results suggest that the association between social amotivation and functioning is generalisable beyond schizophrenia populations to those who are at-risk of developing psychosis. Social amotivation may be an important dimensional clinical construct to be studied across a range of psychiatric conditions. PMID- 26553973 TI - Mapping landscape friction to locate isolated tsetse populations that are candidates for elimination. AB - Tsetse flies are the cyclical vectors of deadly human and animal trypanosomes in sub-Saharan Africa. Tsetse control is a key component for the integrated management of both plagues, but local eradication successes have been limited to less than 2% of the infested area. This is attributed to either resurgence of residual populations that were omitted from the eradication campaign or reinvasion from neighboring infested areas. Here we focused on Glossina palpalis gambiensis, a riverine tsetse species representing the main vector of trypanosomoses in West Africa. We mapped landscape resistance to tsetse genetic flow, hereafter referred to as friction, to identify natural barriers that isolate tsetse populations. For this purpose, we fitted a statistical model of the genetic distance between 37 tsetse populations sampled in the region, using a set of remotely sensed environmental data as predictors. The least-cost path between these populations was then estimated using the predicted friction map. The method enabled us to avoid the subjectivity inherent in the expert-based weighting of environmental parameters. Finally, we identified potentially isolated clusters of G. p. gambiensis habitat based on a species distribution model and ranked them according to their predicted genetic distance to the main tsetse population. The methodology presented here will inform the choice on the most appropriate intervention strategies to be implemented against tsetse flies in different parts of Africa. It can also be used to control other pests and to support conservation of endangered species. PMID- 26553975 TI - Deformation and failure of curved colloidal crystal shells. AB - Designing and controlling particle self-assembly into robust and reliable high performance smart materials often involves crystalline ordering in curved spaces. Examples include carbon allotropes like graphene, synthetic materials such as colloidosomes, or biological systems like lipid membranes, solid domains on vesicles, or viral capsids. Despite the relevance of these structures, the irreversible deformation and failure of curved crystals is still mostly unexplored. Here, we report simulation results of the mechanical deformation of colloidal crystalline shells that illustrate the subtle role played by geometrically necessary topological defects in controlling plastic yielding and failure. We observe plastic deformation attributable to the migration and reorientation of grain boundary scars, a collective process assisted by the intermittent proliferation of disclination pairs or abrupt structural failure induced by crack nucleating at defects. Our results provide general guiding principles to optimize the structural and mechanical stability of curved colloidal crystals. PMID- 26553974 TI - Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. AB - Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ~8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Delta32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward. PMID- 26553976 TI - Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck. AB - The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can be controlled through phase separation of lipids, proteins, and nucleic acids. Collective interactions of multivalent molecules mediated by modular binding domains can induce gelation and phase separation in several cytosolic and membrane-associated systems. The adaptor protein Nck has three SRC-homology 3 (SH3) domains that bind multiple proline-rich segments in the actin regulatory protein neuronal Wiskott-Aldrich syndrome protein (N-WASP) and an SH2 domain that binds to multiple phosphotyrosine sites in the adhesion protein nephrin, leading to phase separation. Here, we show that the 50-residue linker between the first two SH3 domains of Nck enhances phase separation of Nck/N-WASP/nephrin assemblies. Two linear motifs within this element, as well as its overall positively charged character, are important for this effect. The linker increases the driving force for self-assembly of Nck, likely through weak interactions with the second SH3 domain, and this effect appears to promote phase separation. The linker sequence is highly conserved, suggesting that the sequence determinants of the driving forces for phase separation may be generally important to Nck functions. Our studies demonstrate that linker regions between modular domains can contribute to the driving forces for self-assembly and phase separation of multivalent proteins. PMID- 26553977 TI - Shifts in coral reef biogeochemistry and resulting acidification linked to offshore productivity. AB - Oceanic uptake of anthropogenic carbon dioxide (CO2) has acidified open-ocean surface waters by 0.1 pH units since preindustrial times. Despite unequivocal evidence of ocean acidification (OA) via open-ocean measurements for the past several decades, it has yet to be documented in near-shore and coral reef environments. A lack of long-term measurements from these environments restricts our understanding of the natural variability and controls of seawater CO2 carbonate chemistry and biogeochemistry, which is essential to make accurate predictions on the effects of future OA on coral reefs. Here, in a 5-y study of the Bermuda coral reef, we show evidence that variations in reef biogeochemical processes drive interannual changes in seawater pH and Omegaaragonite that are partly controlled by offshore processes. Rapid acidification events driven by shifts toward increasing net calcification and net heterotrophy were observed during the summers of 2010 and 2011, with the frequency and extent of such events corresponding to increased offshore productivity. These events also coincided with a negative winter North Atlantic Oscillation (NAO) index, which historically has been associated with extensive offshore mixing and greater primary productivity at the Bermuda Atlantic Time-series Study (BATS) site. Our results reveal that coral reefs undergo natural interannual events of rapid acidification due to shifts in reef biogeochemical processes that may be linked to offshore productivity and ultimately controlled by larger-scale climatic and oceanographic processes. PMID- 26553978 TI - Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity. AB - Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132 713) and STAT3 (127-722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition. PMID- 26553979 TI - Guanine-vacancy-bearing G-quadruplexes responsive to guanine derivatives. AB - G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and nanodevices. G quadruplexes are normally composed of four Gn (n >= 3) tracts assembled into a core of multiple stacked G-quartet layers. By dimethyl sulfate footprinting, circular dichroism spectroscopy, thermal melting, and photo-cross-linking, here we describe a unique type of intramolecular G-quadruplex that forms with one G2 and three G3 tracts and bears a guanine vacancy (G-vacancy) in one of the G quartet layers. The G-vacancy can be filled up by a guanine base from GTP or GMP to complete an intact G-quartet by Hoogsteen hydrogen bonding, resulting in significant G-quadruplex stabilization that can effectively alter DNA replication in vitro at physiological concentration of GTP and Mg(2+). A bioinformatic survey shows motifs of such G-quadruplexes are evolutionally selected in genes with unique distribution pattern in both eukaryotic and prokaryotic organisms, implying such G-vacancy-bearing G-quadruplexes are present and play a role in gene regulation. Because guanine derivatives are natural metabolites in cells, the formation of such G-quadruplexes and guanine fill-in (G-fill-in) may grant an environment-responsive regulation in cellular processes. Our findings thus not only expand the sequence definition of G-quadruplex formation, but more importantly, reveal a structural and functional property not seen in the standard canonical G-quadruplexes. PMID- 26553980 TI - Accurate estimation of influenza epidemics using Google search data via ARGO. AB - Accurate real-time tracking of influenza outbreaks helps public health officials make timely and meaningful decisions that could save lives. We propose an influenza tracking model, ARGO (AutoRegression with GOogle search data), that uses publicly available online search data. In addition to having a rigorous statistical foundation, ARGO outperforms all previously available Google-search based tracking models, including the latest version of Google Flu Trends, even though it uses only low-quality search data as input from publicly available Google Trends and Google Correlate websites. ARGO not only incorporates the seasonality in influenza epidemics but also captures changes in people's online search behavior over time. ARGO is also flexible, self-correcting, robust, and scalable, making it a potentially powerful tool that can be used for real-time tracking of other social events at multiple temporal and spatial resolutions. PMID- 26553981 TI - Asymptomatic humans transmit dengue virus to mosquitoes. AB - Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized. PMID- 26553982 TI - Optimal directional volatile transport in retronasal olfaction. AB - The ability of humans to distinguish the delicate differences in food flavors depends mostly on retronasal smell, in which food volatiles entrained into the airway at the back of the oral cavity are transported by exhaled air through the nasal cavity to stimulate the olfactory receptor neurons. Little is known whether food volatiles are preferentially carried by retronasal flow toward the nasal cavity rather than by orthonasal flow into the lung. To study the differences between retronasal and orthonasal flow, we obtained computed tomography (CT) images of the orthonasal airway from a healthy human subject, printed an experimental model using a 3D printer, and analyzed the flow field inside the airway. The results show that, during inhalation, the anatomical structure of the oropharynx creates an air curtain outside a virtual cavity connecting the oropharynx and the back of the mouth, which prevents food volatiles from being transported into the main stream toward the lung. In contrast, during exhalation, the flow preferentially sweeps through this virtual cavity and effectively enhances the entrainment of food volatiles into the main retronasal flow. This asymmetrical transport efficiency is also found to have a nonmonotonic Reynolds number dependence: The asymmetry peaks at a range of an intermediate Reynolds number close to 800, because the air curtain effect during inhalation becomes strongest in this range. This study provides the first experimental evidence, to our knowledge, for adaptations of the geometry of the human oropharynx for efficient transport of food volatiles toward the olfactory receptors in the nasal cavity. PMID- 26553983 TI - Conformational signaling required for synaptic plasticity by the NMDA receptor complex. AB - The NMDA receptor (NMDAR) is known to transmit important information by conducting calcium ions. However, some recent studies suggest that activation of NMDARs can trigger synaptic plasticity in the absence of ion flow. Does ligand binding transmit information to signaling molecules that mediate synaptic plasticity? Using Forster resonance energy transfer (FRET) imaging of fluorescently tagged proteins expressed in neurons, conformational signaling is identified within the NMDAR complex that is essential for downstream actions. Ligand binding transiently reduces FRET between the NMDAR cytoplasmic domain (cd) and the associated protein phosphatase 1 (PP1), requiring NMDARcd movement, and persistently reduces FRET between the NMDARcd and calcium/calmodulin-dependent protein kinase II (CaMKII), a process requiring PP1 activity. These studies directly monitor agonist-driven conformational signaling at the NMDAR complex required for synaptic plasticity. PMID- 26553984 TI - RNA-directed DNA methylation enforces boundaries between heterochromatin and euchromatin in the maize genome. AB - The maize genome is relatively large (~ 2.3 Gb) and has a complex organization of interspersed genes and transposable elements, which necessitates frequent boundaries between different types of chromatin. The examination of maize genes and conserved noncoding sequences revealed that many of these are flanked by regions of elevated asymmetric CHH (where H is A, C, or T) methylation (termed mCHH islands). These mCHH islands are quite short (~ 100 bp), are enriched near active genes, and often occur at the edge of the transposon that is located nearest to genes. The analysis of DNA methylation in other sequence contexts and several chromatin modifications revealed that mCHH islands mark the transition from heterochromatin-associated modifications to euchromatin-associated modifications. The presence of an mCHH island is fairly consistent in several distinct tissues that were surveyed but shows some variation among different haplotypes. The presence of insertion/deletions in promoters often influences the presence and position of an mCHH island. The mCHH islands are dependent upon RNA directed DNA methylation activities and are lost in mop1 and mop3 mutants, but the nearby genes rarely exhibit altered expression levels. Instead, loss of an mCHH island is often accompanied by additional loss of DNA methylation in CG and CHG contexts associated with heterochromatin in nearby transposons. This suggests that mCHH islands and RNA-directed DNA methylation near maize genes may act to preserve the silencing of transposons from activity of nearby genes. PMID- 26553985 TI - Chemical dispersants can suppress the activity of natural oil-degrading microorganisms. AB - During the Deepwater Horizon oil well blowout in the Gulf of Mexico, the application of 7 million liters of chemical dispersants aimed to stimulate microbial crude oil degradation by increasing the bioavailability of oil compounds. However, the effects of dispersants on oil biodegradation rates are debated. In laboratory experiments, we simulated environmental conditions comparable to the hydrocarbon-rich, 1,100 m deep plume that formed during the Deepwater Horizon discharge. The presence of dispersant significantly altered the microbial community composition through selection for potential dispersant degrading Colwellia, which also bloomed in situ in Gulf deep waters during the discharge. In contrast, oil addition to deepwater samples in the absence of dispersant stimulated growth of natural hydrocarbon-degrading Marinobacter. In these deepwater microcosm experiments, dispersants did not enhance heterotrophic microbial activity or hydrocarbon oxidation rates. An experiment with surface seawater from an anthropogenically derived oil slick corroborated the deepwater microcosm results as inhibition of hydrocarbon turnover was observed in the presence of dispersants, suggesting that the microcosm findings are broadly applicable across marine habitats. Extrapolating this comprehensive dataset to real world scenarios questions whether dispersants stimulate microbial oil degradation in deep ocean waters and instead highlights that dispersants can exert a negative effect on microbial hydrocarbon degradation rates. PMID- 26553986 TI - Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine. AB - Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH's effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID- 26553987 TI - Human emotions track changes in the acoustic environment. AB - Emotional responses to biologically significant events are essential for human survival. Do human emotions lawfully track changes in the acoustic environment? Here we report that changes in acoustic attributes that are well known to interact with human emotions in speech and music also trigger systematic emotional responses when they occur in environmental sounds, including sounds of human actions, animal calls, machinery, or natural phenomena, such as wind and rain. Three changes in acoustic attributes known to signal emotional states in speech and music were imposed upon 24 environmental sounds. Evaluations of stimuli indicated that human emotions track such changes in environmental sounds just as they do for speech and music. Such changes not only influenced evaluations of the sounds themselves, they also affected the way accompanying facial expressions were interpreted emotionally. The findings illustrate that human emotions are highly attuned to changes in the acoustic environment, and reignite a discussion of Charles Darwin's hypothesis that speech and music originated from a common emotional signal system based on the imitation and modification of environmental sounds. PMID- 26553988 TI - Using prediction markets to estimate the reproducibility of scientific research. AB - Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications. PMID- 26553989 TI - Wetting and phase separation in soft adhesion. AB - In the classic theory of solid adhesion, surface energy drives deformation to increase contact area whereas bulk elasticity opposes it. Recently, solid surface stress has been shown also to play an important role in opposing deformation of soft materials. This suggests that the contact line in soft adhesion should mimic that of a liquid droplet, with a contact angle determined by surface tensions. Consistent with this hypothesis, we observe a contact angle of a soft silicone substrate on rigid silica spheres that depends on the surface functionalization but not the sphere size. However, to satisfy this wetting condition without a divergent elastic stress, the gel phase separates from its solvent near the contact line. This creates a four-phase contact zone with two additional contact lines hidden below the surface of the substrate. Whereas the geometries of these contact lines are independent of the size of the sphere, the volume of the phase separated region is not, but rather depends on the indentation volume. These results indicate that theories of adhesion of soft gels need to account for both the compressibility of the gel network and a nonzero surface stress between the gel and its solvent. PMID- 26553991 TI - Retrading, production, and asset market performance. AB - Prior studies have shown that traders quickly converge to the price-quantity equilibrium in markets for goods that are immediately consumed, but they produce speculative price bubbles in resalable asset markets. We present a stock-flow model of durable assets in which the existing stock of assets is subject to depreciation and producers may produce additional units of the asset. In our laboratory experiments inexperienced consumers who can resell their units disregard the consumption value of the assets and compete vigorously with producers, depressing prices and production. Consumers who have first participated in experiments without resale learn to heed their consumption values and, when they are given the option to resell, trade at equilibrium prices. Reproducibility is therefore the most natural and most effective treatment for suppression of bubbles in asset market experiments. PMID- 26553990 TI - Dynamic allostery governs cyclophilin A-HIV capsid interplay. AB - Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through direct interactions with the viral capsid, by an unknown mechanism. CypA can either promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA) protein sequence. We have examined the role of conformational dynamics on the nanosecond to millisecond timescale in HIV-1 CA assemblies in the escape from CypA dependence, by magic-angle spinning (MAS) NMR and molecular dynamics (MD). Through the analysis of backbone (1)H-(15)N and (1)H-(13)C dipolar tensors and peak intensities from 3D MAS NMR spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is dynamic, particularly in loop regions. The CypA loop in assembled wild-type CA from two strains exhibits unprecedented mobility on the nanosecond to microsecond timescales, and the experimental NMR dipolar order parameters are in quantitative agreement with those calculated from MD trajectories. Remarkably, the CypA loop dynamics of wild-type CA HXB2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type CA assembly in complex with CypA. These results suggest that CypA loop dynamics is a determining factor in HIV-1's escape from CypA dependence. PMID- 26553992 TI - Direct measurements of the coordination of lever arm swing and the catalytic cycle in myosin V. AB - Myosins use a conserved structural mechanism to convert the energy from ATP hydrolysis into a large swing of the force-generating lever arm. The precise timing of the lever arm movement with respect to the steps in the actomyosin ATPase cycle has not been determined. We have developed a FRET system in myosin V that uses three donor-acceptor pairs to examine the kinetics of lever arm swing during the recovery and power stroke phases of the ATPase cycle. During the recovery stroke the lever arm swing is tightly coupled to priming the active site for ATP hydrolysis. The lever arm swing during the power stroke occurs in two steps, a fast step that occurs before phosphate release and a slow step that occurs before ADP release. Time-resolved FRET demonstrates a 20-A change in distance between the pre- and postpower stroke states and shows that the lever arm is more dynamic in the postpower stroke state. Our results suggest myosin binding to actin in the ADP.Pi complex triggers a rapid power stroke that gates the release of phosphate, whereas a second slower power stroke may be important for mediating strain sensitivity. PMID- 26553994 TI - Directed evolution of the tryptophan synthase beta-subunit for stand-alone function recapitulates allosteric activation. AB - Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent catalytic potential using the beta subunit of tryptophan synthase from Pyrococcus furiosus (PfTrpB). As part of its native alphabetabetaalpha complex, TrpB efficiently produces tryptophan and tryptophan analogs; activity drops considerably when it is used as a stand-alone catalyst without the alpha-subunit. Kinetic, spectroscopic, and X-ray crystallographic data show that this lost activity can be recovered by mutations that reproduce the effects of complexation with the alpha-subunit. The engineered PfTrpB is a powerful platform for production of Trp analogs and for further directed evolution to expand substrate and reaction scope. PMID- 26553993 TI - Targeting CD146 with a 64Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas. AB - Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. (64)Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high contrast PET images of small tumor nodules (~ 2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (chi(2) = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors. PMID- 26553995 TI - Unmyelinated type II afferent neurons report cochlear damage. AB - In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear. PMID- 26553996 TI - HAX-1 regulates cyclophilin-D levels and mitochondria permeability transition pore in the heart. AB - The major underpinning of massive cell death associated with myocardial infarction involves opening of the mitochondrial permeability transition pore (mPTP), resulting in disruption of mitochondria membrane integrity and programmed necrosis. Studies in human lymphocytes suggested that the hematopoietic-substrate 1 associated protein X-1 (HAX-1) is linked to regulation of mitochondrial membrane function, but its role in controlling mPTP activity remains obscure. Herein we used models with altered HAX-1 expression levels in the heart and uncovered an unexpected role of HAX-1 in regulation of mPTP and cardiomyocyte survival. Cardiac-specific HAX-1 overexpression was associated with resistance against loss of mitochondrial membrane potential, induced by oxidative stress, whereas HAX-1 heterozygous deficiency exacerbated vulnerability. The protective effects of HAX-1 were attributed to specific down-regulation of cyclophilin-D levels leading to reduction in mPTP activation. Accordingly, cyclophilin-D and mPTP were increased in heterozygous hearts, but genetic ablation of cyclophilin-D in these hearts significantly alleviated their susceptibility to ischemia/reperfusion injury. Mechanistically, alterations in cyclophilin-D levels by HAX-1 were contributed by the ubiquitin-proteosomal degradation pathway. HAX-1 overexpression enhanced cyclophilin-D ubiquitination, whereas proteosomal inhibition restored cyclophilin-D levels. The regulatory effects of HAX-1 were mediated through interference of cyclophilin-D binding to heat shock protein-90 (Hsp90) in mitochondria, rendering it susceptible to degradation. Accordingly, enhanced Hsp90 expression in HAX-1 overexpressing cardiomyocytes increased cyclophilin-D levels, as well as mPTP activation upon oxidative stress. Taken together, our findings reveal the role of HAX-1 in regulating cyclophilin-D levels via an Hsp90-dependent mechanism, resulting in protection against activation of mPTP and subsequent cell death responses. PMID- 26553997 TI - Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow. AB - The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed in neurons. Different neuronal compartments display varying levels of FRET, consistent with different NMDARcd conformations. Agonist binding drives a rapid and transient ion flow independent reduction in FRET between GluN1 subunits within individual NMDARs. Intracellular infusion of an antibody targeting the GluN1 cytoplasmic domain blocks agonist-driven FRET changes in the absence of ion flow, supporting agonist driven movement of the NMDARcd. These studies indicate that extracellular ligand binding to the NMDAR can transmit conformational information into the cell in the absence of ion flow. PMID- 26553998 TI - Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton. AB - In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID- 26553999 TI - FOXO regulates RNA interference in Drosophila and protects from RNA virus infection. AB - Small RNA pathways are important players in posttranscriptional regulation of gene expression. These pathways play important roles in all aspects of cellular physiology from development to fertility to innate immunity. However, almost nothing is known about the regulation of the central genes in these pathways. The forkhead box O (FOXO) family of transcription factors is a conserved family of DNA-binding proteins that responds to a diverse set of cellular signals. FOXOs are crucial regulators of cellular homeostasis that have a conserved role in modulating organismal aging and fitness. Here, we show that Drosophila FOXO (dFOXO) regulates the expression of core small RNA pathway genes. In addition, we find increased dFOXO activity results in an increase in RNA interference (RNAi) efficacy, establishing a direct link between cellular physiology and RNAi. Consistent with these findings, dFOXO activity is stimulated by viral infection and is required for effective innate immune response to RNA virus infection. Our study reveals an unanticipated connection among dFOXO, stress responses, and the efficacy of small RNA-mediated gene silencing and suggests that organisms can tune their gene silencing in response to environmental and metabolic conditions. PMID- 26554000 TI - Self-assembly of smallest magnetic particles. AB - The assembly of tiny magnetic particles in external magnetic fields is important for many applications ranging from data storage to medical technologies. The development of ever smaller magnetic structures is restricted by a size limit, where the particles are just barely magnetic. For such particles we report the discovery of a kind of solution assembly hitherto unobserved, to our knowledge. The fact that the assembly occurs in solution is very relevant for applications, where magnetic nanoparticles are either solution-processed or are used in liquid biological environments. Induced by an external magnetic field, nanocubes spontaneously assemble into 1D chains, 2D monolayer sheets, and large 3D cuboids with almost perfect internal ordering. The self-assembly of the nanocubes can be elucidated considering the dipole-dipole interaction of small superparamagnetic particles. Complex 3D geometrical arrangements of the nanodipoles are obtained under the assumption that the orientation of magnetization is freely adjustable within the superlattice and tends to minimize the binding energy. On that basis the magnetic moment of the cuboids can be explained. PMID- 26554001 TI - Capillary-induced giant elastic dipoles in thin nematic films. AB - Directed and true self-assembly mechanisms in nematic liquid crystal colloids rely on specific interactions between microparticles and the topological defects of the matrix. Most ordered structures formed in thin nematic cells are thus based on elastic multipoles consisting of a particle and nearby defects. Here, we report, for the first time to our knowledge, the existence of giant elastic dipoles arising from particles dispersed in free nematic liquid crystal films. We discuss the role of capillarity and film thickness on the dimensions of the dipoles and explain their main features with a simple 2D model. Coupling of capillarity with nematic elasticity could offer ways to tune finely the spatial organization of complex colloidal systems. PMID- 26554002 TI - Designed protein reveals structural determinants of extreme kinetic stability. AB - The design of stable, functional proteins is difficult. Improved design requires a deeper knowledge of the molecular basis for design outcomes and properties. We previously used a bioinformatics and energy function method to design a symmetric superfold protein composed of repeating structural elements with multivalent carbohydrate-binding function, called ThreeFoil. This and similar methods have produced a notably high yield of stable proteins. Using a battery of experimental and computational analyses we show that despite its small size and lack of disulfide bonds, ThreeFoil has remarkably high kinetic stability and its folding is specifically chaperoned by carbohydrate binding. It is also extremely stable against thermal and chemical denaturation and proteolytic degradation. We demonstrate that the kinetic stability can be predicted and modeled using absolute contact order (ACO) and long-range order (LRO), as well as coarse grained simulations; the stability arises from a topology that includes many long range contacts which create a large and highly cooperative energy barrier for unfolding and folding. Extensive data from proteomic screens and other experiments reveal that a high ACO/LRO is a general feature of proteins with strong resistances to denaturation and degradation. These results provide tractable approaches for predicting resistance and designing proteins with sufficient topological complexity and long-range interactions to accommodate destabilizing functional features as well as withstand chemical and proteolytic challenge. PMID- 26554003 TI - A systematic study of modulation of ADAM-mediated ectodomain shedding by site specific O-glycosylation. AB - Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common process that releases the extracellular domain from the cell and activates cell signaling. Ectodomain shedding occurs in the immediate extracellular juxtamembrane region, which is also where O-glycosylation is often found and examples of crosstalk between shedding and O-glycosylation have been reported. Here, we systematically investigated the potential of site-specific O glycosylation mediated by distinct polypeptide GalNAc-transferase (GalNAc-T) isoforms to coregulate ectodomain shedding mediated by the A Disintegrin And Metalloproteinase (ADAM) subfamily of proteases and in particular ADAM17. We analyzed 25 membrane proteins that are known to undergo ADAM17 shedding and where the processing sites included Ser/Thr residues within +/- 4 residues that could represent O-glycosites. We used in vitro GalNAc-T enzyme and ADAM cleavage assays to demonstrate that shedding of at least 12 of these proteins are potentially coregulated by O-glycosylation. Using TNF-alpha as an example, we confirmed that shedding mediated by ADAM17 is coregulated by O-glycosylation controlled by the GalNAc-T2 isoform both ex vivo in isogenic cell models and in vivo in mouse Galnt2 knockouts. The study provides compelling evidence for a wider role of site specific O-glycosylation in ectodomain shedding. PMID- 26554004 TI - Redistribution of soil water by a saprotrophic fungus enhances carbon mineralization. AB - The desiccation of upper soil horizons is a common phenomenon, leading to a decrease in soil microbial activity and mineralization. Recent studies have shown that fungal communities and fungal-based food webs are less sensitive and better adapted to soil desiccation than bacterial-based food webs. One reason for a better fungal adaptation to soil desiccation may be hydraulic redistribution of water by mycelia networks. Here we show that a saprotrophic fungus (Agaricus bisporus) redistributes water from moist (-0.03 MPa) into dry (-9.5 MPa) soil at about 0.3 cm ? min(-1) in single hyphae, resulting in an increase in soil water potential after 72 h. The increase in soil moisture by hydraulic redistribution significantly enhanced carbon mineralization by 2,800% and enzymatic activity by 250-350% in the previously dry soil compartment within 168 h. Our results demonstrate that hydraulic redistribution can partly compensate water deficiency if water is available in other zones of the mycelia network. Hydraulic redistribution is likely one of the mechanisms behind higher drought resistance of soil fungi compared with bacteria. Moreover, hydraulic redistribution by saprotrophic fungi is an underrated pathway of water transport in soils and may lead to a transfer of water to zones of high fungal activity. PMID- 26554005 TI - Motivation, values, and work design as drivers of participation in the R open source project for statistical computing. AB - One of the cornerstones of the R system for statistical computing is the multitude of packages contributed by numerous package authors. This amount of packages makes an extremely broad range of statistical techniques and other quantitative methods freely available. Thus far, no empirical study has investigated psychological factors that drive authors to participate in the R project. This article presents a study of R package authors, collecting data on different types of participation (number of packages, participation in mailing lists, participation in conferences), three psychological scales (types of motivation, psychological values, and work design characteristics), and various socio-demographic factors. The data are analyzed using item response models and subsequent generalized linear models, showing that the most important determinants for participation are a hybrid form of motivation and the social characteristics of the work design. Other factors are found to have less impact or influence only specific aspects of participation. PMID- 26554007 TI - Dynamic response of desert wetlands to abrupt climate change. AB - Desert wetlands are keystone ecosystems in arid environments and are preserved in the geologic record as groundwater discharge (GWD) deposits. GWD deposits are inherently discontinuous and stratigraphically complex, which has limited our understanding of how desert wetlands responded to past episodes of rapid climate change. Previous studies have shown that wetlands responded to climate change on glacial to interglacial timescales, but their sensitivity to short-lived climate perturbations is largely unknown. Here, we show that GWD deposits in the Las Vegas Valley (southern Nevada, United States) provide a detailed and nearly complete record of dynamic hydrologic changes during the past 35 ka (thousands of calibrated (14)C years before present), including cycles of wetland expansion and contraction that correlate tightly with climatic oscillations recorded in the Greenland ice cores. Cessation of discharge associated with rapid warming events resulted in the collapse of entire wetland systems in the Las Vegas Valley at multiple times during the late Quaternary. On average, drought-like conditions, as recorded by widespread erosion and the formation of desert soils, lasted for a few centuries. This record illustrates the vulnerability of desert wetland flora and fauna to abrupt climate change. It also shows that GWD deposits can be used to reconstruct paleohydrologic conditions at millennial to submillennial timescales and informs conservation efforts aimed at protecting these fragile ecosystems in the face of anthropogenic warming. PMID- 26554006 TI - Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA. AB - Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer. PMID- 26554008 TI - Ultraflexible, large-area, physiological temperature sensors for multipoint measurements. AB - We report a fabrication method for flexible and printable thermal sensors based on composites of semicrystalline acrylate polymers and graphite with a high sensitivity of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit large resistance changes near body temperature under physiological conditions with high repeatability (1,800 times). Device performance is largely unaffected by bending to radii below 700 um, which allows for conformal application to the surface of living tissue. The sensing temperature can be tuned between 25 degrees C and 50 degrees C, which covers all relevant physiological temperatures. Furthermore, we demonstrate flexible active-matrix thermal sensors which can resolve spatial temperature gradients over a large area. With this flexible ultrasensitive temperature sensor we succeeded in the in vivo measurement of cyclic temperatures changes of 0.1 degrees C in a rat lung during breathing, without interference from constant tissue motion. This result conclusively shows that the lung of a warm-blooded animal maintains surprising temperature stability despite the large difference between core temperature and inhaled air temperature. PMID- 26554009 TI - Choosing experiments to accelerate collective discovery. AB - A scientist's choice of research problem affects his or her personal career trajectory. Scientists' combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their efficiency. We represent research problems as links between scientific entities in a knowledge network. We then build a generative model of discovery informed by qualitative research on scientific problem selection. We map salient features from this literature to key network properties: an entity's importance corresponds to its degree centrality, and a problem's difficulty corresponds to the network distance it spans. Drawing on millions of papers and patents published over 30 years, we use this model to infer the typical research strategy used to explore chemical relationships in biomedicine. This strategy generates conservative research choices focused on building up knowledge around important molecules. These choices become more conservative over time. The observed strategy is efficient for initial exploration of the network and supports scientific careers that require steady output, but is inefficient for science as a whole. Through supercomputer experiments on a sample of the network, we study thousands of alternatives and identify strategies much more efficient at exploring mature knowledge networks. We find that increased risk-taking and the publication of experimental failures would substantially improve the speed of discovery. We consider institutional shifts in grant making, evaluation, and publication that would help realize these efficiencies. PMID- 26554010 TI - Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model. AB - Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS. PMID- 26554011 TI - Allosteric N-WASP activation by an inter-SH3 domain linker in Nck. AB - Actin filament networks assemble on cellular membranes in response to signals that locally activate neural Wiskott-Aldrich-syndrome protein (N-WASP) and the Arp2/3 complex. An inactive conformation of N-WASP is stabilized by intramolecular contacts between the GTPase binding domain (GBD) and the C helix of the verprolin-homology, connector-helix, acidic motif (VCA) segment. Multiple SH3 domain-containing adapter proteins can bind and possibly activate N-WASP, but it remains unclear how such binding events relieve autoinhibition to unmask the VCA segment and activate the Arp2/3 complex. Here, we have used purified components to reconstitute a signaling cascade driven by membrane-localized Src homology 3 (SH3) adapters and N-WASP, resulting in the assembly of dynamic actin networks. Among six SH3 adapters tested, Nck was the most potent activator of N WASP-driven actin assembly. We identify within Nck a previously unrecognized activation motif in a linker between the first two SH3 domains. This linker sequence, reminiscent of bacterial virulence factors, directly engages the N-WASP GBD and competes with VCA binding. Our results suggest that animals, like pathogenic bacteria, have evolved peptide motifs that allosterically activate N WASP, leading to localized actin nucleation on cellular membranes. PMID- 26554013 TI - Correction for Choi et al., The SWI/SNF chromatin remodeling complex regulates germinal center formation by repressing Blimp-1 expression. PMID- 26554012 TI - A 3' untranslated region variant in FMR1 eliminates neuronal activity-dependent translation of FMRP by disrupting binding of the RNA-binding protein HuR. AB - Fragile X syndrome is a common cause of intellectual disability and autism spectrum disorder. The gene underlying the disorder, fragile X mental retardation 1 (FMR1), is silenced in most cases by a CGG-repeat expansion mutation in the 5' untranslated region (UTR). Recently, we identified a variant located in the 3'UTR of FMR1 enriched among developmentally delayed males with normal repeat lengths. A patient-derived cell line revealed reduced levels of endogenous fragile X mental retardation protein (FMRP), and a reporter containing a patient 3'UTR caused a decrease in expression. A control reporter expressed in cultured mouse cortical neurons showed an expected increase following synaptic stimulation that was absent when expressing the patient reporter, suggesting an impaired response to neuronal activity. Mobility-shift assays using a control RNA detected an RNA protein interaction that is lost with the patient RNA, and HuR was subsequently identified as an associated protein. Cross-linking immunoprecipitation experiments identified the locus as an in vivo target of HuR, supporting our in vitro findings. These data suggest that the disrupted interaction of HuR impairs activity-dependent translation of FMRP, which may hinder synaptic plasticity in a clinically significant fashion. PMID- 26554014 TI - Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope. AB - The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig 1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID- 26554016 TI - A vacuolar phosphate transporter essential for phosphate homeostasis in Arabidopsis. AB - Inorganic phosphate (Pi) is stored in the vacuole, allowing plants to adapt to variable Pi availability in the soil. The transporters that mediate Pi sequestration into vacuole remain unknown, however. Here we report the functional characterization of Vacuolar Phosphate Transporter 1 (VPT1), an SPX domain protein that transports Pi into the vacuole in Arabidopsis. The vpt1 mutant plants were stunted and consistently retained less Pi than wild type plants, especially when grown in medium containing high levels of Pi. In seedlings, VPT1 was expressed primarily in younger tissues under normal conditions, but was strongly induced by high-Pi conditions in older tissues, suggesting that VPT1 functions in Pi storage in young tissues and in detoxification of high Pi in older tissues. As a result, disruption of VPT1 rendered plants hypersensitive to both low-Pi and high-Pi conditions, reducing the adaptability of plants to changing Pi availability. Patch-clamp analysis of isolated vacuoles showed that the Pi influx current was severely reduced in vpt1 compared with wild type plants. When ectopically expressed in Nicotiana benthamiana mesophyll cells, VPT1 mediates vacuolar influx of anions, including Pi, SO4(2-), NO3(-), Cl(-), and malate with Pi as that preferred anion. The VPT1-mediated Pi current amplitude was dependent on cytosolic phosphate concentration. Single-channel analysis showed that the open probability of VPT1 was increased with the increase in transtonoplast potential. We conclude that VPT1 is a transporter responsible for vacuolar Pi storage and is essential for Pi adaptation in Arabidopsis. PMID- 26554015 TI - Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver. AB - Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5' TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID- 26554017 TI - Heterogeneous lamella structure unites ultrafine-grain strength with coarse-grain ductility. AB - Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems. PMID- 26554018 TI - Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. AB - Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA. PMID- 26554019 TI - Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection. AB - The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to produce the viral structural proteins and a +1 overlapping open reading frame called ORFx, respectively. Here we show that specific mutations of two unpaired adenosines located at the core of the three-helical junction of the honey bee dicistrovirus Israeli acute paralysis virus (IAPV) IRES PKI domain can uncouple 0 and +1 frame translation, suggesting that the structure adopts distinct conformations that contribute to 0 or +1 frame translation. Using a reconstituted translation system, we show that ribosomes assembled on mutant IRESs that direct exclusive 0 or +1 frame translation lack reading frame fidelity. Finally, a nuclear magnetic resonance/small-angle X-ray scattering hybrid approach reveals that the PKI domain of the IAPV IRES adopts an RNA structure that resembles a complete tRNA. The tRNA shape-mimicry enables the viral IRES to gain access to the ribosome tRNA-binding sites and form intermolecular contacts with the ribosome that are necessary for initiating IRES translation in a specific reading frame. PMID- 26554021 TI - Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle. AB - Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability. PMID- 26554023 TI - Correction for O'Dwyer et al., Backbones of evolutionary history test biodiversity theory for microbes. PMID- 26554022 TI - Mapping transient electric fields with picosecond electron bunches. AB - Transient electric fields, which are an important but hardly explored parameter of laser plasmas, can now be diagnosed experimentally with combined ultrafast temporal resolution and field sensitivity, using femtosecond to picosecond electron or proton pulses as probes. However, poor spatial resolution poses great challenges to simultaneously recording both the global and local field features. Here, we present a direct 3D measurement of a transient electric field by time resolved electron schlieren radiography with simultaneous 80-MUm spatial and 3.7 ps temporal resolutions, analyzed using an Abel inversion algorithm. The electric field here is built up at the front of an aluminum foil irradiated with a femtosecond laser pulse at 1.9 * 10(12) W/cm(2), where electrons are emitted at a speed of 4 * 10(6) m/s, resulting in a unique "peak-valley" transient electric field map with the field strength up to 10(5) V/m. Furthermore, time-resolved schlieren radiography with charged particle pulses should enable the mapping of various fast-evolving field structures including those found in plasma-based particle accelerators. PMID- 26554020 TI - QQS orphan gene regulates carbon and nitrogen partitioning across species via NF YC interactions. AB - The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance. PMID- 26554024 TI - TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D dependent Rap1 activation. AB - Sustained activation of extracellular-signal-regulated kinase (ERK) has an important role in the decision regarding the cell fate of B-lymphocytes. Recently, we demonstrated that the diacylglycerol-activated non-selective cation channel canonical transient receptor potential 3 (TRPC3) is required for the sustained ERK activation induced by the B-cell receptor. However, the signalling mechanism underlying TRPC3-mediated ERK activation remains elusive. In the present study, we have shown that TRPC3 mediates Ca(2+) influx to sustain activation of protein kinase D (PKD) in a protein kinase C-dependent manner in DT40 B-lymphocytes. The later phase of ERK activation depends on the small G protein Rap1, known as a downstream target of PKD, whereas the earlier phase of ERK activation depends on the Ras protein. It is of interest that sustained ERK phosphorylation is required for the full induction of the immediate early gene Egr-1 (early growth response 1). These results suggest that TRPC3 reorganizes the BCR signalling complex by switching the subtype of small G-proteins to sustain ERK activation in B-lymphocytes. PMID- 26554025 TI - Potent irreversible P2Y12 inhibition does not reduce LPS-induced coagulation activation in a randomized, double-blind, placebo-controlled trial. AB - Platelets play an important role in the activation of coagulation. P2Y12 receptor inhibition may be beneficial in inflammatory states. Prasugrel, a potent irreversible inhibitor of P2Y12 receptor-induced platelet activation may reduce activation of coagulation in a human LPS (lipopolysaccharide) model. A double blind, randomized, crossover trial with a minimum washout period of 6 weeks was performed. Sixteen subjects were randomly assigned to a treatment group that received prasugrel or placebo 2 h before infusion of a bolus of LPS (2 ng/kg of body weight), whereas four subjects were assigned to a control group receiving prasugrel or placebo without LPS. hcDNA (histone-complexed DNA), coagulation and platelet-specific parameters were measured by enzyme immunoassay. Leucocyte aggregate formation was analysed by flow cytometry, and thromboelastometry was performed. LPS infusion markedly activated coagulation. However, prasugrel did not reduce changes in prothrombin fragments 1 and 2 (F1+2), thrombin-antithrombin complexes, microparticle-associated tissue factor, CD40 ligand, P-selectin, platelet-leucocyte aggregation, hcDNA levels or the coagulation profile measured by thromboelastometry. hcDNA plasma levels increased approximately 6-fold after LPS infusion in both treatment groups, but not in the control groups. Potent irreversible P2Y12 inhibition by prasugrel does not affect LPS-induced coagulation activation. The 6-fold increased hcDNA plasma levels after infusion of LPS indicates the formation of neutrophil extracellular traps during sterile inflammation. PMID- 26554026 TI - The prevalence of medical error related to end-of-life communication in Canadian hospitals: results of a multicentre observational study. AB - BACKGROUND: In the hospital setting, inadequate engagement between healthcare professionals and seriously ill patients and their families regarding end-of-life decisions is common. This problem may lead to medical orders for life-sustaining treatments that are inconsistent with patient preferences. The prevalence of this patient safety problem has not been previously described. METHODS: Using data from a multi-institutional audit, we quantified the mismatch between patients' and family members' expressed preferences for care and orders for life-sustaining treatments. We recruited seriously ill, elderly medical patients and/or their family members to participate in this audit. We considered it a medical error if a patient preferred not to be resuscitated and there were orders to undergo resuscitation (overtreatment), or if a patient preferred resuscitation (cardiopulmonary resuscitation, CPR) and there were orders not to be resuscitated (undertreatment). RESULTS: From 16 hospitals in Canada, 808 patients and 631 family members were included in this study. When comparing expressed preferences and documented orders for use of CPR, 37% of patients experienced a medical error. Very few patients (8, 2%) expressed a preference for CPR and had CPR withheld in their documented medical orders (Undertreatment). Of patients who preferred not to have CPR, 174 (35%) had orders to receive it (Overtreatment). There was considerable variability in overtreatment rates across sites (range: 14 82%). Patients who were frail were less likely to be overtreated; patients who did not have a participating family member were more likely to be overtreated. CONCLUSIONS: Medical errors related to the use of life-sustaining treatments are very common in internal medicine wards. Many patients are at risk of receiving inappropriate end-of-life care. PMID- 26554027 TI - Gap junctions are essential for murine primordial follicle assembly immediately before birth. AB - The reserve of primordial follicles determines the reproductive ability of the female mammal over its reproductive life. The primordial follicle is composed of two types of cells: oocytes and surrounding pre-granulosa cells. However, the underlying mechanism regulating primordial follicle assembly is largely undefined. In this study, we found that gap junction communication (GJC) established between the ovarian cells in the perinatal mouse ovary may be involved in the process. First, gap junction structures between the oocyte and surrounding pre-granulosa cells appear at about 19.0 dpc (days post coitum). As many as 12 gap junction-related genes are upregulated at birth, implying that a complex communication may exist between ovarian cells, because specifically silencing the genes of individual gap junction proteins, such as Gja1, Gja4 or both, has no influence on primordial follicle assembly. On the other hand, non specific blockers of GJC, such as carbenoxolone (CBX) and 18alpha-glycyrrhetinic acid (AGA), significantly inhibit mouse primordial follicle assembly. We proved that the temporal window for establishment of GJC in the fetal ovary is from 19.5 dpc to 1 dpp (days postpartum). In addition, the expression of ovarian somatic cell (OSC)-specific genes, such as Notch2, Foxl2 and Irx3, was negatively affected by GJC blockers, whereas oocyte-related genes, such as Ybx2, Nobox and Sohlh1, were hardly affected, implying that the establishment of GJC during this period may be more important to OSCs than to oocytes. In summary, our results indicated that GJC involves in the mouse primordial follicle assembly process at a specific temporal window that needs Notch signaling cross-talking. PMID- 26554028 TI - Novel regulation and functional interaction of polycistronic miRNAs. AB - The importance of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore coexpressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of miR-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in pleiotropic developmental defects. This novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and, thus, likely reflects the more general cis-regulation of expression of individual miRNAs. Collectively, our results uncover a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift a biological response. PMID- 26554029 TI - Peptide release promoted by methylated RF2 and ArfA in nonstop translation is achieved by an induced-fit mechanism. AB - Here we report that the specificity of peptide release in the ribosome on a nonstop mRNA by ArfA and RF2 is achieved by an induced-fit mechanism. Using RF2 that is methylated on the glutamine of its GGQ motif (RF2(m)), we show that methylation substantially increases the rate of ArfA/RF2-catalyzed peptide release on a nonstop mRNA that does not occupy the ribosomal A site, but has only a modest effect on k(cat) by the same proteins on longer nonstop mRNAs occupying the A site of the mRNA channel in the ribosome. Our data suggest that enhancement in the kcat of peptide release by ArfA and RF2 under the cognate decoding condition is the result of favorable conformational changes in the nonstop complex. We demonstrate a shared mechanism between canonical and nonstop termination, supported by similarities in the kinetic mechanisms in antibiotic inhibition and methylation-correlated enhancement in the rate of peptide release. Despite these similarities, our data suggest that nonstop termination differs from canonical pathway in the downstream event of recycling. PMID- 26554030 TI - High-throughput sequencing of human plasma RNA by using thermostable group II intron reverse transcriptases. AB - Next-generation RNA-sequencing (RNA-seq) has revolutionized transcriptome profiling, gene expression analysis, and RNA-based diagnostics. Here, we developed a new RNA-seq method that exploits thermostable group II intron reverse transcriptases (TGIRTs) and used it to profile human plasma RNAs. TGIRTs have higher thermostability, processivity, and fidelity than conventional reverse transcriptases, plus a novel template-switching activity that can efficiently attach RNA-seq adapters to target RNA sequences without RNA ligation. The new TGIRT-seq method enabled construction of RNA-seq libraries from <1 ng of plasma RNA in <5 h. TGIRT-seq of RNA in 1-mL plasma samples from a healthy individual revealed RNA fragments mapping to a diverse population of protein-coding gene and long ncRNAs, which are enriched in intron and antisense sequences, as well as nearly all known classes of small ncRNAs, some of which have never before been seen in plasma. Surprisingly, many of the small ncRNA species were present as full-length transcripts, suggesting that they are protected from plasma RNases in ribonucleoprotein (RNP) complexes and/or exosomes. This TGIRT-seq method is readily adaptable for profiling of whole-cell, exosomal, and miRNAs, and for related procedures, such as HITS-CLIP and ribosome profiling. PMID- 26554031 TI - Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs. AB - The functions of the major mammalian cytoplasmic poly(A) binding protein, PABPC1, have been characterized predominantly in the context of its binding to the 3' poly(A) tails of mRNAs. These interactions play important roles in post transcriptional gene regulation by enhancing translation and mRNA stability. Here, we performed transcriptome-wide CLIP-seq analysis to identify additional PABPC1 binding sites within genomically encoded mRNA sequences that may impact on gene regulation. From this analysis, we found that PABPC1 binds directly to the canonical polyadenylation signal in thousands of mRNAs in the mouse transcriptome. PABPC1 binding also maps to translation initiation and termination sites bracketing open reading frames, exemplified most dramatically in replication-dependent histone mRNAs. Additionally, a more restricted subset of PABPC1 interaction sites comprised A-rich sequences within the 5' UTRs of mRNAs, including Pabpc1 mRNA itself. Functional analyses revealed that these PABPC1 interactions in the 5' UTR mediate both auto- and trans-regulatory translational control. In total, these findings reveal a repertoire of PABPC1 binding that is substantially broader than previously recognized with a corresponding potential to impact and coordinate post-transcriptional controls critical to a broad array of cellular functions. PMID- 26554033 TI - Activation of multiple growth factor signalling pathways is frequent in meningiomas. AB - A minority of meningiomas are difficult to treat with surgery or radiotherapy, and chemotherapeutic alternatives are limited. This study aims to better understand pathways that are active in meningiomas, in order to direct future treatment strategies. We investigated the expression and activation of multiple growth factor receptors, their ligands and downstream signalling pathways in 30 meningiomas using immunohistochemistry. Expression was correlated with chromosome 22q loss. Membrane expression of VEGF receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR)beta was seen in 83% of tumors, Axl in 70%, EGFR in 50% and insulin-like growth factor receptor in 47%. Expression was similar in low and high-grade tumors, but membrane EGFR expression was not seen in tumors showing chromosome 22q loss (P < 0.05). Expression of ligands (IGF, NRG, VEGF, Gas 6), and signalling proteins (Mek, Erk, Jnk, Akt) and pS6RP, was widespread. Western blot confirmed widespread Axl expression and supported selective expression of EGFR in NF2-intact meningiomas. The majority of meningiomas express and show activation of multiple growth factor receptors and their signalling pathways, irrespective of tumor grade. In addition to previously reported receptors, Axl offers a new therapeutic target. The findings also suggest that anti-EGFR based therapies may be less effective in meningiomas with 22q loss. PMID- 26554032 TI - Long-range RNA pairings contribute to mutually exclusive splicing. AB - Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks. PMID- 26554034 TI - Periodical measurement of urine volume in the bladder during sleep: Temporary volume reduction suggestive of absorption. AB - OBJECTIVES: To clarify the variance of urine volume in the urinary bladder during sleep. METHODS: Overnight measurements of urinary bladder capacity during sleep were carried out using transabdominal real-time 3-D ultrasound or an automatic capacity recorder, Yuririn, in 24 volunteers of various ages. RESULTS: Two types of patterns were observed in the increasing curve of capacity; namely, gradual elevation pattern when overnight urine production was less than functional bladder capacity and steep-flat pattern when it was more than functional bladder capacity. During steep-flat pattern, bladder capacity reached levels of the functional bladder capacity quickly, then maintained steadily at that level until morning without awakening. Temporary volume reduction, which might be suggestive of water absorption from urine in the bladder, occurred occasionally, when the volumes of urine reached functional bladder capacity. CONCLUSIONS: A considerable amount of urine in the bladder diminishes without micturition during sleep to maintain a good level of sleep. This is the first report suggesting the possibility of water absorption from urine within the human urinary bladder in a fully physiological situation. PMID- 26554035 TI - Introduction to 'Origin and evolution of the nervous system'. AB - In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems. PMID- 26554036 TI - Early metazoan life: divergence, environment and ecology. AB - Recent molecular clock studies date the origin of Metazoa to 750-800 million years ago (Ma), roughly coinciding with evidence from geochemical proxies that oxygen levels rose from less than 0.1% present atmospheric level (PAL) to perhaps 1-3% PAL O2. A younger origin of Metazoa would require greatly increased substitution rates across many clades and many genes; while not impossible, this is less parsimonious. Yet the first fossil evidence for metazoans (the Doushantuo embryos) about 600 Ma is followed by the Ediacaran fossils after 580 Ma, the earliest undisputed bilaterians at 555 Ma, and an increase in the size and morphologic complexity of bilaterians around 542 Ma. This temporal framework suggests a missing 150-200 Myr of early metazoan history that encompasses many apparent novelties in the early evolution of the nervous system. This span includes two major glaciations, and complex marine geochemical changes including major changes in redox and other environmental changes. One possible resolution is that animals of these still unknown Cryogenian and early Ediacaran ecosystems were relatively simple, with highly conserved developmental genes involved in cell-type specification and simple patterning. In this model, complex nervous systems are a convergent phenomenon in bilaterian clades which occurred close to the time that larger metazoans appeared in the fossil record. PMID- 26554037 TI - Early animal evolution and the origins of nervous systems. AB - Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour. PMID- 26554038 TI - Unlocking the early fossil record of the arthropod central nervous system. AB - Extant panarthropods (euarthropods, onychophorans and tardigrades) are hallmarked by stunning morphological and taxonomic diversity, but their central nervous systems (CNS) are relatively conserved. The timing of divergences of the ground pattern CNS organization of the major panarthropod clades has been poorly constrained because of a scarcity of data from their early fossil record. Although the CNS has been documented in three-dimensional detail in insects from Cenozoic ambers, it is widely assumed that these tissues are too prone to decay to withstand other styles of fossilization or geologically older preservation. However, Cambrian Burgess Shale-type compressions have emerged as sources of fossilized brains and nerve cords. CNS in these Cambrian fossils are preserved as carbon films or as iron oxides/hydroxides after pyrite in association with carbon. Experiments with carcasses compacted in fine-grained sediment depict preservation of neural tissue for a more prolonged temporal window than anticipated by decay experiments in other media. CNS and compound eye characters in exceptionally preserved Cambrian fossils predict divergences of the mandibulate and chelicerate ground patterns by Cambrian Stage 3 (ca 518 Ma), a dating that is compatible with molecular estimates for these splits. PMID- 26554040 TI - Molecular clocks and the early evolution of metazoan nervous systems. AB - The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. PMID- 26554039 TI - Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution. AB - Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of 'evo-devo'. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters-the partitioned brain of arthropods and the ventral centralized nerve cords of annelids-a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. PMID- 26554041 TI - The origin and evolution of chordate nervous systems. AB - In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum. PMID- 26554042 TI - Convergent evolution of complex brains and high intelligence. AB - Within the animal kingdom, complex brains and high intelligence have evolved several to many times independently, e.g. among ecdysozoans in some groups of insects (e.g. blattoid, dipteran, hymenopteran taxa), among lophotrochozoans in octopodid molluscs, among vertebrates in teleosts (e.g. cichlids), corvid and psittacid birds, and cetaceans, elephants and primates. High levels of intelligence are invariantly bound to multimodal centres such as the mushroom bodies in insects, the vertical lobe in octopodids, the pallium in birds and the cerebral cortex in primates, all of which contain highly ordered associative neuronal networks. The driving forces for high intelligence may vary among the mentioned taxa, e.g. needs for spatial learning and foraging strategies in insects and cephalopods, for social learning in cichlids, instrumental learning and spatial orientation in birds and social as well as instrumental learning in primates. PMID- 26554043 TI - Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity. AB - Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. PMID- 26554044 TI - Evolution of brain elaboration. AB - Large, complex brains have evolved independently in several lineages of protostomes and deuterostomes. Sensory centres in the brain increase in size and complexity in proportion to the importance of a particular sensory modality, yet often share circuit architecture because of constraints in processing sensory inputs. The selective pressures driving enlargement of higher, integrative brain centres has been more difficult to determine, and may differ across taxa. The capacity for flexible, innovative behaviours, including learning and memory and other cognitive abilities, is commonly observed in animals with large higher brain centres. Other factors, such as social grouping and interaction, appear to be important in a more limited range of taxa, while the importance of spatial learning may be a common feature in insects with large higher brain centres. Despite differences in the exact behaviours under selection, evolutionary increases in brain size tend to derive from common modifications in development and generate common architectural features, even when comparing widely divergent groups such as vertebrates and insects. These similarities may in part be influenced by the deep homology of the brains of all Bilateria, in which shared patterns of developmental gene expression give rise to positionally, and perhaps functionally, homologous domains. Other shared modifications of development appear to be the result of homoplasy, such as the repeated, independent expansion of neuroblast numbers through changes in genes regulating cell division. The common features of large brains in so many groups of animals suggest that given their common ancestry, a limited set of mechanisms exist for increasing structural and functional diversity, resulting in many instances of homoplasy in bilaterian nervous systems. PMID- 26554046 TI - Where is my mind? How sponges and placozoans may have lost neural cell types. AB - Recent phylogenomic evidence suggests that ctenophores may be the sister group to the rest of animals. This phylogenetic arrangement opens the possibility that sponges and placozoans could have lost neural cell types or that the ctenophore nervous system evolved independently. We critically review evidence to date that has been put forth in support of independent evolution of neural cell types in ctenophores. We observe a reluctance in the literature to consider a lost nervous system in sponges and placozoans and suggest that this may be due to historical bias and the commonly misconstrued concept of animal complexity. In support of the idea of loss (or modification beyond recognition), we provide hypothetical scenarios to show how sponges and placozoans may have benefitted from the loss and/or modification of their neural cell types. PMID- 26554045 TI - Brain evolution by brain pathway duplication. AB - Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID- 26554047 TI - Vertebrate brains and evolutionary connectomics: on the origins of the mammalian 'neocortex'. AB - The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated 'cortical' manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple 'subcortical' groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as 'evolutionary connectomics', revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian 'neocortex', hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial 'columns' in the mammalian sensory and motor cortices. The molecular properties of these 'nuclei' in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID- 26554048 TI - Evolution of eumetazoan nervous systems: insights from cnidarians. AB - Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system-in particular the nervous system of the anthozoan Nematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution. PMID- 26554051 TI - [BLADDER EXSTROPHY AND RECTAL BLADDER]. PMID- 26554049 TI - An option space for early neural evolution. AB - The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input-output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems. PMID- 26554052 TI - [TRAUMATIC RUPTURE OF CORPUS CAVENOSUM]. PMID- 26554053 TI - [Liver fibrosis can be assessed by non-invasive ultrasound elastography]. AB - Diagnosis and assessment of liver fibrosis is of great importance for initiating treatment and starting hepatocellular carcinoma surveillance in patients with established cirrhosis. Liver biopsy is still considered the gold standard for liver fibrosis staging, however; it is far from perfect. Non-invasive assessment of liver fibrosis is becoming more available and is well tolerated. This review describes the feasibility and reliability of two elastography methods: transient elastography and Acoustic Radiation Force. PMID- 26554050 TI - Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution. AB - Prerequisite for tracing nervous system evolution is understanding of the body plan, feeding behaviour and locomotion of the first animals in which neurons evolved. Here, a comprehensive scenario is presented for the diversification of cell types in early metazoans, which enhanced feeding efficiency and led to the emergence of larger animals that were able to move. Starting from cup-shaped, gastraea-like animals with outer and inner choanoflagellate-like cells, two major innovations are discussed that set the stage for nervous system evolution. First, the invention of a mucociliary sole entailed a switch from intra- to extracellular digestion and increased the concentration of nutrients flowing into the gastric cavity. In these animals, an initial nerve net may have evolved via division of labour from mechanosensory-contractile cells in the lateral body wall, enabling coordinated movement of the growing body that involved both mucociliary creeping and changes of body shape. Second, the inner surface of the animals folded into metameric series of gastric pouches, which optimized nutrient resorption and allowed larger body sizes. The concomitant acquisition of bilateral symmetry may have allowed more directed locomotion and, with more demanding coordinative tasks, triggered the evolution of specialized nervous subsystems. Animals of this organizational state would have resembled Ediacarian fossils such as Dickinsonia and may have been close to the cnidarian-bilaterian ancestor. In the bilaterian lineage, the mucociliary sole was used mostly for creeping, or frequently lost. One possible remnant is the enigmatic Reissner's fibre in the ventral neural tube of cephalochordates and vertebrates. PMID- 26554054 TI - [Methotrexate may be a useful corticosteroid reducing treatment of severe asthma]. AB - Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation. PMID- 26554055 TI - [Optic disc oedema]. AB - Optic disc oedema describes the nonspecific, localized swelling of the optic nerve head regardless of aetiology. Therefore, differentiating among the various aetiologies depends on a thorough history and knowledge of the clinical characteristics of the underlying conditions. Papilloedema strictly refers to optic disc oedema as a consequence of elevated intracranial pressure. It is usually a bilateral condition and visual function is preserved until late. Optic disc oedema caused by an anterior optic neuropathy is usually unilateral and accompanied by the loss of visual function. PMID- 26554056 TI - [Treatment with amiodarone]. AB - Amiodarone is an effective antiarrhythmic drug for supra-ven-tri-cular and ventricular arrhythmias. A majority of patients treated with amiodarone suffer from mild adverse events, however, serious life-threatening adverse events caused by amiodarone are also seen. This review describes the pharmacology, interac tions, side and adverse effects of amiodarone and highlights the importance of a systematic interdisciplinary follow-up protocol for outpatients treated with amiodarone. PMID- 26554057 TI - [Case study shows that the case manager function for cancer patients is used unevenly across the different cancer forms]. AB - This case study of the obligatory case manager function for cancer patients explores by whom and for what the function is used. It draws on quantitative data from a database, focus group interviews with case managers at Rigshospitalet and telephone interviews with patients and relatives. The conclusion is that across the different cancer forms patients are using the function unevenly. This can probably be explained by the varying organizational set-ups for patient trajectories across departments. The individual patients and relatives express satisfaction with the information and assistance received from the case managers. PMID- 26554058 TI - [Weight loss guidance for patients with heart failure is complex]. AB - Observation studies have shown that overweight in patients with congestive heart failure is associated with lower risk of all-cause mortality and cardiovascular mortality. This is called the paradox of obesity. Other studies do not support this correla-tion. In conclusion, a stable body weight is recommended for patients with a BMI of 25-29.9 kg/m2. If BMI >= 40 kg/m2, weight loss is recommended. There is no consensus for weight reduction if BMI is 30-40 kg/m2. PMID- 26554059 TI - [Case managers experience improved trajectories for cancer patients after implementation of the case manager function]. AB - Case managers are increasingly used to optimize trajectories for patients. This study is based on a questionnaire among case managers in cancer care, aiming at the clarification of the func-tion and its impact on especially patient safety, when handing over the responsibility. The results show a major variation in how the function is organized, the level of competence and the task to be handled. The responsibility has in general been nar-rowed to department level. Overall, the case managers believe that the function has optimized pathways for cancer patients and improved safety, but barriers persist. PMID- 26554060 TI - [Obese asthma patients have poorer asthma control]. AB - Current literature indicates that asthma is more prevalent among obese individuals. In addition, studies have shown that higher body mass index (BMI), particularly BMI >= 30 kg/m2, is associated with poorer asthma control and asthma related quality of life. Furthermore, growing evidence suggests that obese patients with asthma respond less favourably to inhaled corticosteroids compared to non-obese patients. Moreover, longitudinal studies indicate that weight reduction improves asthma control. Therefore, preventing and treating obesity should be an integrated part of asthma management. PMID- 26554061 TI - [Chronic salicylate poisoning is a challenging diagnosis]. AB - Chronic salicylate poisoning is often seen in elderly patients as a result of an unintended overdosage, a change in metabolism or kidney function. The symptoms are often unspecific. This case report is about a 55-year-old man who was unconscious when admitted to hospital, and who died three hours after admission. An autopsy and a toxicological test showed a deadly level of salicylate in his blood. Afterwards, his wife told that he had complained about a sudden hearing loss, and that his behaviour had changed prior to his death. It is important to keep this diagnosis in mind when treating especially elderly patients. PMID- 26554062 TI - [Not Available]. PMID- 26554064 TI - [In Process Citation]. PMID- 26554065 TI - [In Process Citation]. PMID- 26554066 TI - [In Process Citation]. PMID- 26554067 TI - [In Process Citation]. PMID- 26554068 TI - [In Process Citation]. PMID- 26554069 TI - Response. PMID- 26554070 TI - Response. PMID- 26554071 TI - [Practical references for Herpes zoster vaccination]. PMID- 26554072 TI - [Identifying alcohol problem solution]. PMID- 26554073 TI - [Chronic patient flat rate: Barmer GEK relents]. PMID- 26554074 TI - The clinical prediction rule for whiplash associated disorders. PMID- 26554075 TI - [Prevention act: is now "Check-up 18" covered?]. PMID- 26554076 TI - Response. PMID- 26554077 TI - Response. PMID- 26554078 TI - Response. PMID- 26554079 TI - Response. PMID- 26554080 TI - Response. PMID- 26554081 TI - Entraining the free-running circadian clocks of blind people. PMID- 26554083 TI - Empowering citizen scientists. Scientists should consider engaging more with the DIYbio community. PMID- 26554082 TI - Individual risk factors for physician boundary violations: the role of attachment style, childhood trauma and maladaptive beliefs. AB - OBJECTIVE: The assessment and remediation of boundary-challenged healthcare professionals is enhanced through examination of individual risk factors. We assessed three such factors--attachment style, childhood trauma and maladaptive beliefs--in 100 attendees (mostly physicians) of a CME professional boundaries course. We propose a theoretical model which draws a causal arc from childhood maltreatment through insecure attachment and maladaptive beliefs to elevated risk for boundary violations. METHODS: We administered the Experiences in Close Relationship Questionnaire (ECR-R), Childhood Trauma Questionnaire (CTQ), and Young Schema Questionnaire (YSQ) to 100 healthcare professionals (mostly physicians) attending a CME course on professional boundaries. Experts rated participant autobiographies to determine attachment style and early adversities. Correlations and relationships among self- and expert ratings and between different risk factors were examined. RESULTS: Five percent of participants reported CTQ total scores in the moderate to severe range; eleven percent reported moderate to severe emotional neglect or emotional abuse. Average attachment anxiety and attachment avoidance were low, and more than half of participants were rated "secure" by experts. Childhood maltreatment was correlated with attachment anxiety and avoidance and predicted expert-rated insecure attachment and maladaptive beliefs. CONCLUSION: Our findings support a potential link between childhood adversity and boundary difficulties, partly mediated by insecure attachment and early maladaptive beliefs. Furthermore, these results suggest that boundary education programs and professional wellness programs may be enhanced with a focus on sequelae of childhood maltreatment, attachment and common maladaptive thinking patterns. PMID- 26554084 TI - Daniel J. Muller. PMID- 26554085 TI - Points of Significance. Bayesian networks. PMID- 26554086 TI - Sensors and probes Building lasers inside cells. PMID- 26554087 TI - Hot, Hotter, and Hottest Trends in alpha-Synuclein Research. PMID- 26554088 TI - Neuroscience. Algae are the best engineers of optogenetic inhibitors. PMID- 26554089 TI - Genomics. where the G-quadruplexes are. PMID- 26554090 TI - Proteomic. Navigating the negative-mode proteome. PMID- 26554091 TI - Synthetic biology. Stop the presses. PMID- 26554092 TI - Genomics. Micro-C maps of genome structure. PMID- 26554093 TI - Imaging. RNA catch and release. PMID- 26554094 TI - Colonic mucosal alpha-synuclein lacks specificity as a biomarker for Parkinson disease. PMID- 26554095 TI - Author response. PMID- 26554096 TI - Response. PMID- 26554097 TI - Response. PMID- 26554098 TI - [Treatment of fistula after surgery of head and neck cancer]. PMID- 26554099 TI - [Diagnosis and management of genetical hearing impairment]. PMID- 26554100 TI - Response from Dr. Vandewalle. PMID- 26554101 TI - White lesion of tongue. Morsicatio linguarum. PMID- 26554102 TI - Pioglitazone. PMID- 26554103 TI - Diagnosis of diabetes. AB - The diagnosis of diabetes is not as straightforward as it may seem. this brief communication describes how to diagnose [and not to diagnose] diabetes in a simple manner. This information will be of use to general practitioners as well as students of diabetology. PMID- 26554105 TI - Evidence-Based Review and Discussion Points. PMID- 26554106 TI - Alzheimer dementia--a problem of individuals, families, medicine and society. PMID- 26554107 TI - A clinical study on the influence of suturing material on oral wound healing. AB - BACKGROUND/AIM: Suture materials play an important role in healing, enabling reconstruction and reassembly of tissue separated by the surgical procedure or trauma, and at the same time facilitating and promoting healing and hemostasis. Suture materials are used daily in oral surgery, and are considered to be substances most commonly implanted in human body. The aim of this clinical study was to examine the speed of wound healing and complications incidence, after the use of three different absorbable synthetic suture materials in oral surgery (catgut, Dexon and Vicryl rapide), and to ascertain which one is the most suitable for oral surgery. METHODS: The study was conducted on 96 patients undergoing root resection or surgical extraction of third molars. Each of the suture materials (catgut, Dexon and Vicryl rapide) was used for 8 root resections and 8 surgical third molar extractions in the maxilla, as well as in the mandible (a total of 32 surgical interventions for each suture material). RESULTS: The faster wound healing was obtained with Vicryl rapide compared to other two suturing material tested. There was no significant difference regarding the presence of local reaction in all the three groups of patients on the 21st postoperative day. CONCLUSION: The results of our clinical study point out that Vycril- rapid contributes more than catgut or Dexon to faster healing of human wounds, with fewer incidences of wound dehiscence and milder local reactions. PMID- 26554108 TI - Emotional reactions in patients after frontal lobe stroke. AB - BACKGROUND/AIM: Emotional reactions have been documented after tumor lesions and the other damages of the brain. The aim of this paper was to examine the correlation between frontal lobe lesions and emotional reactions in patients with stroke. METHODS: The research included 118 patients after stroke. Lesion localization was defined on computed axial tomography records, whereas the area and perimeter of lesion were measured by AutoCAD 2004 software. Examinations by means of the Hamilton Rating Scale for Anxiety and Depression (HRSA and HRSD) were carried out 11-40 days after stroke. Statistic data were processed by simple linear/nonlinear regression, Cox's and the generalized linear model. RESULTS: A higher frequency of emotional reactions, i.e. anxiety, was determined in women after stroke (p = 0.024). A negative correlation between the lesion size and the intensity of anxiety manifestations was determined (Spearman's r = -0.297; p = 0.001). Anxiety was more frequent in patients with frontal lobe lesions in the dominant hemisphere (interaction: frontal lesion * hand dominant hemisphere, p = 0.017). Also, HRSD score values showed the tendency for lesser decline in case of greater frontal lobe lesions in relation to lesions of other regions of prosencephalon (interaction: frontal lesion * lesion area, p = 0.001). CONCLUSION: The results of this study indicate the correlation between evolutionary younger structures of the central nervous system and emotional reactions of man. Therefore, it is necessary to undertake proper early psychopharmacotherapy in the vulnerable group of patients. PMID- 26554109 TI - The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease. AB - BACKGROUND/AIM. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. METHODS: The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (rho = -0.015), parameters of both obesity (R = 0.437;p < 0.001) and insulin resistance (R = 0.374; p < 0.01). Decreasing in the level of adiponecrin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease ih adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 +/- 402.65 pg/mL. CONCLUSIONS: The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes. PMID- 26554110 TI - Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs. AB - BACKGROUND/AIM: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. METHODS: A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the war surgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach). Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. RESULTS: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. CONCLUSION: Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics (ceftriaxone and clindamycin) was applied. The use of this method should be limited to individual and strictly controlled cases in civil practice for now. PMID- 26554111 TI - Analysis of over-the-counter medicines use among nursing students. AB - BACKGROUND/AIM: The use of over-the-counter (OTC) medication is widespread among the adult and student populations in Slovenia. The aim of the study was to analyse the prevalence of OTC medicines use among nursing students with respect to sociodemographic characteristics. METHODS: A total of 241 nursing students in the Faculty of Health Sciences, Ljubljana, were included in the cross-sectional study. A questionnaire was created for the purposes of the study. Statistical analysis was performed with SPSS 20. Descriptive statistics, t-test and the contingency coefficient were calculated. Statistical significance was set at the p-value of < 0.05. RESULTS: The study showed that the use of prescription drugs was significantly higher in women (p = 0.029), students living in rural areas (p = 0.005) and students who described themselves as being of bad health (p = 0.008). At the same time, a third of the respondents had been taking one OTC medicine within the last month; those taking several prescription drugs commonly administered several over-the-counter medicines (p = 0.027). Women used OTC medicines to treat pain and fever (p = 0.001), respiratory issues (p = 0.015), and fungal infections (p < 0.000) more often than men. OTC medicines were also used to treat minor mental health issues by a higher proportion of respondents over 21 years of age (p = 0.005) and women (p < 0.000), while over-the-counter medicines for treating skin conditions were more frequently used in rural areas (p = 0.006). CONCLUSION: Nursing students tend to use OTC medicines on their own accord, receiving instructions for safe use with their purchase, which points to adequate promotion of safe use of medications in Slovenia. Men's assessment of their personal health tends to be better than that of women, who also use medication more frequently. A connection between poor health and a higher incidence of the use of OTC medicines was established. The use of OTC medicines to treat minor mental health issues increased with age and was more typical of women. The results obtained demonstrate the importance of personal control over the safe use of medicines, motivation for personal good health and a healthy lifestyle. PMID- 26554112 TI - Copper and zinc concentrations in atherosclerotic plaque and serum in relation to lipid metabolism in patients with carotid atherosclerosis. AB - BACKGROUND/AIM: Some oligoelements are now investigated as possibly having a role in atherosclerosis. The aim of this study was to compare the concentrations of copper and zinc in the serum and carotid plaque and parameters of lipid metabolism in patients with different morphology of carotid atherosclerotic plaque. METHODS: Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients (mean age 64 +/- 7). The control group consisted of 27 patients (mean age 58 +/- 9), without carotid atherosclerosis. Atheroscletoric plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Copper and zinc concentrations in the plaque, carotid artery and serum were measured by atomic absorption spectrophotometry. RESULTS: Serum copper concentrations were statistically significantly higher in the patients with hemorrhagic in comparison to those with calcified plaque (1.2 +/- 0.9 umol/L vs 0.7 +/- 0.2 umol/L, respectively; p = 0.021). Zinc concentrations were statistically significantly lower in plaques of the patients with fibrolipid in comparison to those with calcified plaques (22.1 +/- 16.3 g/g vs 38.4 +/- 25.8 ug/g, respectively; p = 0.024). A negative significant correlation was found for zinc and triglycerides in the serum in all the patients (r = -0.52, p = 0.025). In the control group we also demonstrated a positive significant correlation for low-density lipoprotein cholesterol and copper in the serum (r = 0.54, p = 0.04). CONCLUSION: The data obtained in the current study are consistent with the hypothesis that high copper and lower zinc levels may contribute to atherosclerosis and its sequelae as factors in a multifactorial disease. Further studies are necessary in order to conclude whether high concentration of copper and zinc in the serum could be risk factors for atherosclesrosis. PMID- 26554113 TI - Children's health risk assessment based on the content of toxic metals Pb, Cd, Cu and Zn in urban soil samples of Podgorica, Montenegro. AB - BACKGROUND/AIM: Due to their low tolerance to pollutants and hand-to-mouth pathways the health risk is very high in children's population. The aim of this study was to evaluate risk to children's health based on the content of heavy metals in urban soil samples from Podgorica, Montenegro. This study included the investigation of several toxic metals such as Pb, Cd, Cu and Zn in soil samples from public parks and playgrounds. METHODS: Sampling was conducted in a period October-November, 2012. Based on cluster analysis, soil samples were divided into two groups related to similarity of metal content at examinated locations: the group I--near by recreational or residential areas of the city, and the group II- near traffic roads. Concentration of toxic metals, in urban soil samples were determined by a graphite furnace atomic absorption spectrometry (Pb and Cd) and by inductively coupled plasma optical emission spectrometry technique after microwave digestion. Due to exposure to urban soil, non-cancerogenic index hazardous index (HI) for children was estimated using 95th percentile values of total metal concentration. The value of the total (ingestion, dermal and inhalation) HI is calculated for maximum, minimum and the average concentration of metals for children. RESULTS: Mean concentrations of Pb, Cd, Cu and Zn in the surface layer of the studied urban soils were 85.91 mg/kg, 2.8 mg/kg and 52.9 mg/kg and 112.5 mg/kg, respectively. Samples from group II showed higher metal content compared to group I. Urbanization and traffic are the main sources of pollution of the urban soils of Podgorica. Most of the samples (93.5%) had a high Pb content, 12.9% of the samples had a higher content of Cd, while Cu and Zn were within the limits prescribed by national legislation. At one location the level of security for lead is HI = 0.8 and very closed to maximum acceptable value of 1. It is probably the result of intensive traffic near by. CONCLUSION: All metals investigated showed relatively higher concentrations at sites that were close to industrial places and high ways. The mean concentrations of Pb and Zn and maximum concentrations of Pb, Cd, and Zn were higher than presented values in the National Regulation. PMID- 26554114 TI - Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: the influence of gender and comedication. AB - BACKGROUND/AIM. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppressive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D) ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. METHODS. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872) of the renal transplant patients. The patients were monitored in the period 2010 2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC) were measured by chemiluminescence microparticles immunoassay. RESULTS. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD) per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine). while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. CONCLUSION: A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster elimination of tacrolimus in the females was also seen, with the exception of the doses > 0.25 mg/kg. Tacrolimus exposure in the pantoprazole-treated patients was significantly less expressed, while in patients treated with CCB amplodipine the tacrolimus C/D ratio was significantly higher in comparison with the patients not treated with them. PMID- 26554115 TI - Age-related changes of vitamin C levels in aqueous humour. AB - BACKGROUND/AIM: Age-related cataract is a common disease among senior population. Vitamin C is the most effective reducing hydrosoluble antioxidant causing reduction in the levels of free radicals in crystaline lens. The aim of this study was to evaluate the age-related change of vitamin C (L-ascorbic acid) level in the aqueous humor of patients with senile cataract. METHODS: This prospective study included 74 patients, divided into 3 age groups, with age-related cataract, underwent routine phaco cataract surgery with intraocular lens implantation. Aqueous humor was aspirated from 74 eyes at the beginning of phacoemulsification. The levels of vitamin C (L-ascorbic acid) in aqueous humor were determined with high-performance liquid chromatography (HPLC). RESULTS: The average age of pa- tients included in the study was 65 +/- 9.85 years (54-87 years). The level of vitamin C in aqueous humor was 152.78 +/- 7.0125 ug/mL in the group A (50-59 years), 134.15 +/- 5.1569 ug/mL in the group B (60-69 years) and 106.51 +/- 5.44 ug/mL in the group C (over 70 years). CONCLUSION: The amount of vitamin C in aqueous humor of patients with age-related cataract is decreasing with age. There was a statistically significant change (p < 0.001) of vitamin C aqueous concentration in the patients of different age. This decrease could play a role in susceptibility to cataract formation in older population. PMID- 26554116 TI - Neurotoxic effects of oxygen in hyperbaric environment: A case report. AB - INTRODUCTION: Oxygen is an essential element of life in aerobic organisms. However, if not controlled, inhalation of oxygen under increased pressure in conditions of hyperbaric oxygen therapy can lead to serious damage and even death. CASE REPORT: We presented a 20-year-old male who had begun exhibiting symptoms of epilepsy during diving test in a hyperbaric chamber while inhaling 100% oxygen. He was immediately taken off oxygen mask and started breathing air and began rapid decompression. He lost consciousness, began foaming at the mouth, and had a series of tonic spasms. The patient was previously completely healthy and not on any medications. He was admitted for emergency treatment in our hospital, where he was treated for epilepsy. On admission, he complained of muscle and joint pain, and had erythematous changes on the forehead, neck and chest. All these changes occurred after leaving the hyperbaric chamber. Bloodwork revealed leukocytosis with neutrophil (Leukocytosis 16.0 x 10(9)/L (reference values 4.00-11.00 x 10(9)/L), Neutrophili 13 x 10(9)/L (reference values 1.9-8.0 x 10(9)/L), with elevated enzymes aspartate aminotransferase (AST) 56 U/L (reference values 0-37 U/L), alanin aminotransferase (ALT) 59 U/L, (reference values 25-65 U/L), creatine kinase (CK) 649 U/L, (reference values 32-300 U /L), lactate dehydrogenase (LDH) 398 U/L (reference values 85-227 U/L). Because of pain and his condition we began treatment in a hyperbaric chamber at a pressure of 2.0 ATA for 70 minutes, resulting in a reduction of symptoms and objective recovery of the patient. Within 24 h, repeated laboratory tests showed a reduction of leukocytosis (13 x 109/L and neutrophils (7.81 x 109/L), and the gradual reduction of the enzymes AST (47 U/L), ALT (50 U/L, CK (409 U/L), LDH (325 U/L). Since head CT and EEG were normal, epilepsy diagnosis was ruled out. This fact, along with medical tests, facilitated the differential diagnosis and confirmed that this was a case of neurotoxic effects of oxygen while the patient was in a hyperbaric chamber, not epileptic seizures. CONCLUSION: This case report suggests that in patients with symptoms of epileptic seizures while undergoing treatment in a hyperbaric chamber, it is always important to think of neurotoxic effects of pure oxygen which occurs at higher pressures and with a longer inhalation of 100% oxygen. In these patients, reexposure to hyperbaric conditions leads to recovery. This effect is important in daily inhalation of 100% oxygen under hyperbaric conditions which is why the use of pure oxygen is controlled and diving is allowed in shallow depths and for a limited time. PMID- 26554117 TI - Unrecognised adrenergic symptoms and the delayed diagnosis of urinary bladder paraganglioma. AB - INTRODUCTION: Paraganglioma is a rare neuroendocrine neoplasm that may arise from the extra-adrenal autonomic paraganglia. Urinary bladder paraganglioma is typically presented as repeated episodes of palpitations, headache or blood pressure rise immediately after micturition. Management of these tumors includes radical surgical treatment with preoperative antihypertensive preparation, and a life-long follow-up. CASE REPORT: We presented a middle-age female patient with functional urinary bladder paraganglioma, with a 3-year history of repeated episodes of abdominal pain, dysuria and hematuria. After obtaining more precise anamnestic data, the patient reported occasional simultaneous presence of mild adrenergic symptoms, that did not cause any particular attention at first. Morphological and biohumoral examinations suggested paraganglioma of the urinary bladder. Open partial cystectomy was performed, detecting a submucosal mass, while immunohistochemical analysis confirmed the presence of chromaffin tissue. Clinical manifestations, diagnostic approach, management and histopathological findings of urinary bladder paraganglioma are discussed. CONCLUSION: Since the prognosis with localized paraganglioma is good, we underlined the importance of a well-timed, accurate and detailed medical history in all the patients with even mild, inexplicable micturition-provoked adrenergic symptomatology. PMID- 26554118 TI - Typical chest pain and precordial leads ST-elevation in patients with pacemakers- are we always looking at an acute myocardial infarction? AB - INTRODUCTION: Electrocardiographic (ECG) diagnosis of acute myocardial infarction (AMI) in patients with paced rhythm is difficult. Sgarbossa's criteria represent helpful diagnostic ECG tool. CASE REPORT: A 57-year-old female patient with paroxysmal atrial fibrillation and a permanent pacemaker presented in the Emergency Department with prolonged typical chest pain and ECG recording suggestive for AMI. Documented ECG changes correspond to the first Sgarbossa's criterion for AMI in patients with dual pacemakers (ST-segment elevation of 5 mn in the presence of the negative QRS complex). The patient was sent to catheterization lab where coronary angiogram reveled normal findings. ECG changes occurred due to pericardial reaction following two interventions: pacemaker implantation a month before and radiofrequency catheter ablation of AV junction two weeks before presentation in Emergency Department. CONCLUSION: This case report points out to the limitations of proposed criteria that aid in the recognition of AMI in patients with underlying paced rhythm and possible cause(s) of transient electrocardiographic abnormalities. PMID- 26554119 TI - Surgical treatment of orbital floor blowout fracture in children: A case report. AB - INTRODUCTION: Orbital floor blowout fracture is a common traumatic lesion of the craniofacial complex, but rarely in children population, consequently representing challenge in surgical treatment. Timely diagnosis and surgical treatment prevent the probability of the occurrence of the functional complications. CASE REPORT: We presented surgical treatment of on 8-year-old girl with a blowout orbital floor fracture one month after the injury. The predominant symptoms were: ocular bulb motility disorder with consecutive strabismus and double vision. Orbital floor reconstruction was made by an autogenous mandibular symphyseal graft. A year after the orbital floor reconstruction additional correction of strabismus was performed due to functional disorder of the bulbomotor muscles. CONCLUSION: Delayed surgical treatment of blowout orbital floor fracture in children leads to unsatisfactory functional results in the majority of cases. In such a situation surgical correction of strabismus is necessary in order to obtain functionally quality vision and satisfactory aesthetic appearance. PMID- 26554120 TI - Multiple lateral sinus pericranii--A case report. AB - INTRODUCTION: Sinus pericranii is a rare vascular anomaly. It is characterized by abnormal communication between the extracranial and intracranial venous system, usually involving the superior sagittal sinus and occasionally the transverse sinus. Off the midline lesions are extremely rare. Multiplicity, associated venous lakes, venous angioma and lateral location are unusual and unique presentation of sinus pericranii. CASE REPORT: A case of multiple congenital off midline sinus pericranii in the left frontotemporal and parietal region is presented. Magnetic resonance imaging showed an extracranial vascular anomaly connected with the intracranial venous system through abnormal diploic or emissary veins. The lesions were removed completely by surgery. CONCLUSION: Sinus pericranii is a rare vascular malformation with unique clinical and radiological features. Sinus pericranii may cause fatal complications, and it must be treated by surgical or endovascular procedures. PMID- 26554121 TI - Legionnaires' disease: Is it really that rare in Serbia? PMID- 26554122 TI - SOCIAL MEDIA: Like or Not Like? PMID- 26554123 TI - On the broom: Anchorage physician promotes the ancient sport of curling. PMID- 26554124 TI - Farsighted. Interview by Kathy Espin. PMID- 26554125 TI - PERTUSSIS. PMID- 26554126 TI - The promise of rapid detection of active pulmonary tuberculosis in rural Alaska. AB - BACKGROUND: The process by which active pulmonary tuberculosis (TB) is detected can be tediously slow in rural and often roadless Alaska, where several hundred air or boat miles can separate a patient from a chest x-ray and/or sputum collection. Additionally, the only TB reference lab in the state is many hundreds of air miles away, albeit centrally located in Anchorage. Under such conditions, it may take up to a week to process serial sputum AFB smears. This can result in either delayed onset of treatment or unnecessary empiric treatment, all while safety for the community is being considered. This dilemma often results in precautionary hospital isolation of a patient who might otherwise have been able to travel home by air. This article proposes a roadmap for remote health care settings that might bridge our current TB diagnostic ability to a better way in the future. METHODS: Current TB diagnostic guidelines in our area (Yukon Kuskokwim Delta) were reviewed for integration of the Xpert MTB/ RIF assay with the purpose of improving TB health care while emphasizing patient benefits and cost savings. RESULTS: A clinical guideline that integrates the rapid TB assay into the current TB diagnostic algorithms for adults and adolescents is proposed. Crude cost savings at our hospital resulting from this guideline are estimated to be $316,000 per year. CONCLUSION: The proven utility of a new rapid TB diagnostic, the Xpert MTB/RIF assay, offers the promise of more efficient TB medical care, improved patient human rights and improved hospital and community environmental safety, all with likely huge reduced health care costs in remote Alaska. PMID- 26554127 TI - [EXPERIMENTAL TESTING OF THE OPERATOR'S PERCEPTION OF SYMBOLIC INFORMATION ON THE HELMET-MOUNTED DISPLAY DEPENDING ON THE STRUCTURAL COMPLEXITY OF VISUAL ENVIRONMENT]. AB - The experiments showed that pilot's perception of symbolic information on the helmet-mounted display (HMD) depends on type of HMD (mono- or binocular), and structural complexity of the background image. Complex background extends time and increases errors in perception, particularly when monocular HMD is used. In extremely complicated visual situations (symbolic information on a background intricately structured by supposition of a TV image on real visual environment) significantly increases time and lowers precision of symbols perception no matter what the HMD type. PMID- 26554128 TI - [STRUCTURAL-FUNCTIONAL STATUS OF THE LYMPH TISSUE OF MICE LYMPHATIC NODES FOLLOWING THE 30-DAY FLIGHT ONBOARD SPACECRAFT BION-M1]. AB - The article reports the results of studying the lymph tissue of mesenteric and cervical lymphatic nodes in C57BL/6N mice after the 30-day orbital flight onboard biosatellite Bion-M1. Histological and morphometric investigations revealed changes in the ratio of the nodes structural-functional zones and microstructure. Reductions in reticular cells, plasmocytes, macrophages and blasts in the nodes point to degradation of both humoral and cellular immunity. PMID- 26554129 TI - [SHIFTS IN URINE PROTEIN PROFILE DURING DRY IMMERSION]. AB - The study was aimed at tracking the proteomic profile of urine in 8 normal volunteers to 5-day dry immersion (DI). The proteome composition was determined by chromatography-mass spectrometry on high-efficient on-line liquid nano chromatograph Agilent 1100; complementary information about the protein spectra was obtained by dint of mass-spectrometer MaXis Impact 4G and hybrid mass spectrometer LTQ-FT. Functional associations between proteins and biological functions were analyzed using computer system ANDCell (Associative Networks Discovery in Cells). A total of 256 proteins were identified; for 43 proteins difference in the detection rate during the baseline data collection and on DI day 4 exceeded 20%. PMID- 26554130 TI - [REARRANGEMENT OF THE LYMPH TISSUE IN THE MICE SPLEEN AND JEJUNUM WALL DURING THE GROUND-BASED REPRODUCTION OF THE CONDITIONS OF ANIMAL MAINTENANCE IN THE BIOSATTELITE BION-M1 MISSION]. AB - Purpose of the investigation was microscopic examination of changes in cyto architectonics of the spleen and jejunum lymph (immune) tissue in 19-20-week C57BL/6N male mice exposed to some conditions their counterparts had lived in during the 30-d Bion-M1 mission (ground experiment). Local deviations in reactions of the morphofunctional zones of these organs were found. In the spleen, reaction in the centers of lymph nodules generation or the B-lymphocytes maturation zone grows strong. Changes in the cell composition of periarterial lymph sheaths that constitute the morphological site of T-lymphocytes accumulation suggest inhibition of its functional activity. Cell composition of the jejunum wall structure implies a decline of the jejunal immune activity. Our investigation of the organs taken from the ground control mice maintained in the flight BIOS-MLZh module evidences that unceasing noise, hypokinesia, isolation, and paste-like feed weaken general immunity of laboratory animals. PMID- 26554131 TI - [DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE]. AB - The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/MUm to 1.6 keV/MUm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect. PMID- 26554132 TI - [CALCULATION OF RADIATION LOADS ON THE ANTHROPOMORPHIC PHANTOM ONBOARD THE SPACE STATION IN THE CASE OF ADDITIONAL SHIELDING]. AB - The paper presents the results of calculating doses from space ionizing radiation for a modeled orbital station cabin outfitted with an additional shield aimed to reduce radiation loads on cosmonaut. The shield is a layer with the mass thickness of -6 g/cm2 (mean density = 0.62 g/cm3) that covers the outer cabin wall and consists of wet tissues and towels used by cosmonauts for hygienic purposes. A tissue-equivalent anthropomorphic phantom imitates human body. Doses were calculated for the standard orbit of the International space station (ISS) with consideration of the longitudinal and transverse phantom orientation relative to the wall with or without the additional shield. Calculation of dose distribution in the human body improves prediction of radiation loads. The additional shield reduces radiation exposure of human critical organs by -20% depending on their depth and body spatial orientation in the ISS compartment. PMID- 26554133 TI - [INVESTIGATION OF THE COMBINED DISINFECTANT EFFECT OF ULTRA-HIGH FREQUENCY ENERGY AND SILVER ON WATER IN FLOW]. AB - The paper is dedicated to the results of investigating the combined effect of ultra-high frequency (UHF) energy and silver on contaminated water. Silver was used both in the ion form at the minimal concentration of 0.01-0.02 mg/l and solid state, i.e. a silver wire spiral. The purpose was to determine UHF-regimes of the flowing water disinfection process in the presence of silver. PMID- 26554134 TI - [MORBIDITY OF SUBMARINE CREW SAILORS IN LONG-DISTANCE CRUISES]. AB - Morbidity among the personnel of a Kola-based (beyond the Arctic circle) atomic (ASM) and diesel-powered (DSM) submarines in the course of long-distance cruises in different waters of the world ocean was studied. Statistics was collected from the reports of submarine medical officers since 1969. Levels and causes of morbidity were analyzed. According to the data of many years' observations, within the structure of primary diseases of military contractors on cruises the leading place has been occupied by respiratory disorders followed by skin and subcutaneous fat problems, and digestive diseases. Incidence of chronic diseases among ASM and DSM personnel was evaluated. The authors raise the issue of dental care quality provided to submariners. PMID- 26554135 TI - [ON HUMAN BODY REACTION TO A CHANGED GEOMAGNETIC BACKGROUND]. AB - Purpose of the work was to test the concept about existence of a heliobiological relation in the Earth's middle-latitude region for which to analyze, as an example, frequency of circulatory disease exacerbation, mental and behavior disorders, and respiratory diseases (bronchial asthma). The subject and object of the experimental statistic survey have been dwellers of city of Murom (Vladimir region) located in middle-latitude geomagnetic region Phi ~ 53 degrees. The source material in the investigation was medical data of the Murom ambulance service and geophysical data of the Borok geomagnetic observatory (Yaroslavl region). The survey went on 3 years from February, 1985 till December, 1987 and coincided with the rise of the 11th solar cycle. The largest number of calls to the ambulance service due to acute circulatory condition, mental or behavior disorders, respiratory diseases (bronchial asthma particularly) and their fatal outcome fell on periods of long absence of high-frequency geomagnetic pulsation within the frequency range of human biorhythms. PMID- 26554136 TI - [ON THE INTRACRANIAL HYPERTENSION IN ASTRONAUTS DURING LONG-TERM MICROGRAVITY]. PMID- 26554137 TI - [SEVENTEENTH MEETING OF THE US/RUSSIAN JOINT WORKING GROUP ON THE SPACE BIOMEDICAL AND BIOLOGICAL SCIENCES RESEARCH]. PMID- 26554139 TI - Interview With Richard J. Umbdenstock, FACHE, President and CEO of the American Hospital Association. PMID- 26554138 TI - EDITORIAL. PMID- 26554140 TI - A Rapidly Adaptable Management System. PMID- 26554141 TI - Worksite Wellness: Culture and Controversy. PMID- 26554142 TI - Integrating Strategic and Operational Decision Making Using Data-Driven Dashboards: The Case of St. Joseph Mercy Oakland Hospital. AB - Hospitals have invested and continue to invest heavily in building information systems to support operations at various levels of administration. These systems generate a lot of data but fail to effectively convert these data into actionable information for decision makers. Such ineffectiveness often is attributed to a lack of alignment between strategic planning and information technology (IT) initiatives supporting operational goals. We present a case study that illustrates how the use of digital dashboards at St. Joseph Mercy Oakland (SJMO) Hospital in Pontiac, Michigan, was instrumental in supporting such an alignment. Driven by a focus on key performance indicators (KPIs), dashboard applications also led to other tangible and intangible benefits. An ability to track KPIs over time and against established targets, with drill-down capabilities, allowed leadership to hold staff members accountable for achieving their performance targets. By displaying the dashboards in prominent locations (such as operational unit floors, the physicians' cafeteria, and nursing stations), SJMO ushered in transparency in the planning and monitoring processes. The need to develop KPI metrics and drive data collection efforts became ingrained in the work ethos of people at every level of the organization. Although IT-enabled dashboards have been instrumental in supporting this cultural transformation, the focus of investment was the ability of technology to make collective vision and action the responsibility of all stakeholders. PMID- 26554143 TI - PRACTITIONER APPLICATION. PMID- 26554144 TI - What Determines the Surgical Patient Experience? Exploring the Patient, Clinical Staff, and Administration Perspectives. AB - Hospitals are increasingly concerned with enhancing surgical patient experience given that Medicare reimbursements are now tied in part to patient satisfaction. Surgical patients' experience may be influenced by several factors (e.g., integration of care, technical aspects of care), which are ranked differently in importance by clinicians and patients. Strategies designed to improve patient experience can be informed by our research, which examines the determinants of the surgical patient experience from the perspective of multiple healthcare team members. We conducted 12 focus groups with surgical patients, family members, physicians, nurses, and hospital administrators at one acute care, for-profit hospital in a western state and analyzed the content for determinants of the overall surgical patient experience. Specifically, we analyzed the content of the conversations to determine how frequently participants discussed the determinants of the surgical patient experience and how positive, negative, or neutral the comments were. The study's findings suggest that surgical patients and members of the healthcare team have similar views regarding the most important factors in the patient experience-namely, interdisciplinary relationships, technical infrastructure, and staffing. The study results will be used to improve care in this facility and can inform the development of initiatives aimed at improving the surgical patient experience elsewhere. Our study could serve as a model for how other facilities can analyze the surgical patient experience from the perspectives of different stakeholders and improve their performance on the basis of data directly relevant to their organization. PMID- 26554145 TI - PRACTITIONER APPLICATION. PMID- 26554146 TI - A Review of Electronic Hand Hygiene Monitoring: Considerations for Hospital Management in Data Collection, Healthcare Worker Supervision, and Patient Perception. AB - Healthcare-associated infections (HAIs) in U.S. acute care hospitals lead to a burden of $96-$147 billion annually on the U.S. health system and affect 1 in 20 hospital patients (Marchetti & Rossiter, 2013). Hospital managers are charged with reducing and eliminating HAIs to cut costs and improve patient outcomes. Healthcare worker (HCW) hand hygiene (HH) practice is the most effective means of preventing the spread of HAIs, but compliance is at or below 50% (McGuckin, Waterman, & Govednik, 2009). For managers to increase the frequency of HCW HH occurrences and improve the quality of HH performance, companies have introduced electronic technologies to assist managers in training, supervising, and gathering data in the patient care setting. Although these technologies offer valuable feedback regarding compliance, little is known in terms of capabilities in the clinical setting. Less is known about HCW or patient attitudes if the system allows feedback to be shared. Early-adopting managers have begun to examine their experiences with HH technologies and publish their findings. We review peer-reviewed research on infection prevention that focused on the capabilities of these electronic systems, as well as the related research on HCW and patient interactions with electronic HH systems. Research suggests that these systems are capable of collecting data, but the results are mixed regarding their impact on HH compliance, reducing HAIs, or both and their costs. Research also indicates that HCWs and patients may not regard the technology as positively as industry or healthcare managers may have intended. When considering the adoption of electronic HH monitoring systems, hospital administrators should proceed with caution. PMID- 26554147 TI - PRACTITIONER APPLICATION. PMID- 26554148 TI - Using Hybrid Change Strategies to Improve the Patient Experience in Outpatient Specialty Care. AB - The emerging changes in healthcare impose significant burdens on integrated outpatient specialty services with respect to setting patient expectations, handling outside medical records; and coordinating specialty appointments scheduling. Moreover, because of the evolution of the electronic health record and its widespread use, it is critical that patient and physician interaction is maintained and clerical tasks are minimized. In the context of increased government regulation, declining reimbursement, and the rise of new payment models, outpatient practices need to be reimagined so that they are more efficient for the patient and the provider. The redesign of integrated outpatient specialty services can be accomplished only through teamwork, innovation, and efficient use of technology. To address these challenges, the Department of Medicine at Mayo Clinic in Scottsdale, Arizona, implemented an ideal practice design initiative that leveraged a hybrid set of change strategies. The change strategy, which was initiated after examination of current practices and design options, engaged key stakeholders and patients. A number of enablers and barriers to adoption were identified as a result of the implementation experience. PMID- 26554149 TI - PRACTITIONER APPLICATION. PMID- 26554151 TI - Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging. AB - Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis. PMID- 26554152 TI - Relief of Oxidative Stress Using Curcumin and Glutathione Functionalized ZnO Nanoparticles in HEK-293 Cell Line. AB - To elucidate the effect of zinc oxide nanoparticles (ZnO-NPs) with different surface modifications in relieving the oxidative stress in cultured human embryonic kidney cells (HEK-293) following investigation was performed. Oxidative stress was artificially induced by hydrogen peroxide in HEK-293 cell culture and its management was studied. Alkyl amines modified ZnO-NPs with curcumin and reduced glutathione (GSH) functionalization was used in managing oxidative stress and had shown promising results. ZnO-NPs used in this study were synthesized via non-aqueous sol-gel method and FESEM characterisation showed them of spherical shape of about 20-50 nm size with amine, curcumin and GSH functionalization. UV visible and FTIR spectroscopic characterizations confirmed functionalization of ZnO-NPs. Decrease in oxidative stress was found with the dose-dependent culture of HEK-293 cells with these functionalized ZnO-NPs. Cell viability and morphology, as observed using AFM and inverted microscope, was retained with the prescribed dosages of the functionalized nanoparticles while at higher dosages they caused cytotoxicity and death. Diethylamine (DEA) modified ZnO-NPs and their functionalization with GSH and curcumin were found more effective in managing oxidative stress in cells. Present study could help in designing economical and bio-compatible functionalized non-toxic nanoparticles designed for managing oxidative stress leading to possible therapeutical and medicinal uses. PMID- 26554153 TI - CD20 Antibody-Conjugated Immunoliposomes for Targeted Chemotherapy of Melanoma Cancer Initiating Cells. AB - Cancer initiating cells (CIC) are tumorigenic cancer cells that have properties similar to normal stem cells. CD20 is a phenotype of melanoma CIC that is responsible for melanoma drug resistance. Vincristine (VCR) is commonly used in melanoma therapy; however, it has been found ineffective against CIC. To target CD20+ melanoma CIC, we prepared VCR-containing immunoliposomes that were conjugated to CD20 antibodies (VCR-Lip-CD20). The drug release profile and the antibody-mediated targeting of the immunoliposomes were optimized to target CD20+ melanoma CIC. The immunoliposomes had desirable particle size (163 nm), drug encapsulation efficiency (91.8%), and drug release profile. We demonstrated that these immunoliposomes could successfully target more than 55% of CD20+ Chinese Hamster Ovary cells (CHO-CD20) even when the CHO-CD20 cells accounted for only 0.1% of a mixed population of CHO-CD20 and CHO cells. After treating WM266-4 melanoma mammospheres for 96 h, the ICo values of the drug delivered in VCR-Lip CD20, VCR-Lip (VCR liposomes), and VCR were found to be 53.42, 98.99, and 99.09 MUg/mL, respectively, suggesting that VCR-Lip-CD20 was 1.85 times more effective than VCR-Lip and VCR. VCR-Lip-CD20 could almost completely remove the tumorigenic ability of WM266-4 mammospheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. Significantly, VCR-Lip-CD20 could selectively kill CD20+ melanoma CIC in populations of WM266-4 cells both in vitro and in vivo. We demonstrated that VCR-Lip-CD20 has the potential to efficiently target and kill CD20+ melanoma CIC. PMID- 26554154 TI - Heparin and Vascular Endothelial Growth Factor Loaded Poly(L-lactide-co caprolactone) Nanofiber Covered Stent-Graft for Aneurysm Treatment. AB - Restenosis caused by thrombopoiesis is one of the biggest hinders of endovascular stent-graft used in small-diameter vessels. Rapid endothelialization of the lumen of stent is a promising approach to prevent thrombosis. In this study, we aimed at loading heparin, a potent anticoagulants, and vascular endothelial growth factor (VEGF) into the core of poly(L-lactide-co-caprolactone) nanofiber via emulsion electrospinning. The nanofiber was covered on the stent and applied in the treatment of vascular diseases such as aneurysm. The morphologies of the emulsion electrospun nanofibers and core--shell structure were observed by scanning electron microscope and laser scanning confocal microscope. The release profiles of heparin and VEGF, degradation rate of nanofiber mats and cell proliferation in vitro were investigated. It was found that the release of both heparin and VEGF from the nanofiber lasted for more than 30 days without serious initial burst release. The degradation rate of nanofiber mats containing heparin and VEGF was faster than that of pure PLCL nanofiber mats. Moreover, the released VEGF could promote the proliferation of Pig iliac endothelial cells (PIECs) cultured on the nanofiber mat, which was of great benefit to stent endothelialization. The results of digital subtraction angiography (DSA) follow up indicated the aneurysm was obliterated by separating the aneurysm dome from the blood circulation and the parent artery kept long-term patency. Results of the study demonstrated that the heparin and VEGF loaded nanofiber could provide an approach to fabricate covered stent-graft with properties of anticoagulation and induction of rapid endothelialization. PMID- 26554155 TI - Modulating the Growth and Imatinib Sensitivity of Chronic Myeloid Leukemia Stem/Progenitor Cells with Pullulan/MicroRNA Nanoparticles In Vitro. AB - Chronic myeloid leukemia (CML) originates from normal hematopoietic stem cells acquiring Philadelphia chromosome (Ph) to generate BCR-ABL fusion gene whose protein product has deregulated tyrosine kinase activity. Specific inhibitors against BCR-ABL, such as Imatinib mesylate (IM), have greatly improved CML management; however, no single agent is a cure yet. Delivery of microRNA (miRNA) using non-viral vectors has been utilized to inhibit various cancer cells; however, the efficacy of this approach to target CML stem/progenitor cells has not been elucidated. In this study, we firstly validated that spermine-introduced pullulan (Ps) was a robust non-viral vector for delivery of miRNA to CML cells, including the CD34+ cells from clinical isolates. We then found that the miR 181a/RALA (V-ral simian leukemia viral oncogene homolog A) axis was aberrantly expressed in the CML CD34+ cells. The delivery of miR-181a specifically inhibited the growth of CML CD34+ cells, possibly via the inhibition of RALA. In contrast, miR-181a did not evidently affect the normal hematopoietic CD34+ cells. In addition, miR-181a increased IM sensitivity of the CD34+ CML cells. Taken together, we have therefore demonstrated that the delivery of miR-181a using Ps to CML stem/progenitor cells leads to their growth inhibition and enhancement of IM sensitivity, which will possibly be beneficial to CML treatment. PMID- 26554156 TI - Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and lontophoresis. AB - The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and a new BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer. PMID- 26554150 TI - Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging. AB - Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug's therapeutic effectiveness while reducing adverse side effects associated wifh high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an "active" molecular marker targeted approach would be-beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery, of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID- 26554157 TI - Synergistic Effect of Immunoliposomal Gemcitabine and Bevacizumab in Glioblastoma Stem Cell-Targeted Therapy. AB - Glioblastoma stem cells have been shown to confer chemoresistance and radioresistance, leading to angiogenesis and the recurrence of tumors in glioblastoma multiforme. Combination therapy targeting glioblastoma stem cells and anti-angiogenesis has been a focus of treatment strategies because of the enhanced efficacy achieved by dual inhibition of tumor proliferation and nutrient delivery. In this study, glioblastoma stem cells and glioblastoma stem cell induced angiogenesis in glioblastoma multiforme were challenged by combined treatment with anti-CD133 monoclonal antibody conjugated liposomes encapsulating gemcitabine and bevacizumab. Both liposomal encapsulation and conjugation of an anti-CD133 antibody significantly enhanced the cytotoxicity of gemcitabine toward glioblastoma stem cells in vitro. Moreover, combined treatment with this gemcitabine formulation and bevacizumab significantly inhibited tube formation, migration, and proliferation of endothelial cells in vitro. The antitumor efficacy of immunoliposomal gemcitabine and bevacizumab combination therapy in a xenograft model was significantly greater than that of monotherapy, presumably reflecting the enhanced effects on glioblastoma stem cells themselves and glioblastoma stem cell-induced angiogenesis caused by synergistic interactions between the two drugs. Moreover, combination therapy prolonged the mean survival time of xenografted mice. Taken altogether, our results suggest that combined therapy with immunoliposomal gemcitabine and bevacizumab shows promise for the treatment of glioblastoma multiforme. PMID- 26554158 TI - In Vivo Near-Infrared Photodynamic Therapy Based on Targeted Upconversion Nanoparticles. AB - Upconversion nanoparticles have shown to be a promising prospect for biological detection and photodynamic therapy (PDT). The focus of this study was to develop an upconversion nanoparticle modified with a targeting peptide and photosensitizer for near-infrared photodynamic therapy. To produce a tumor targeting nanophotosensitizer with near-infrared excitation, NaYF4:Yb/Er upconversion nanoparticles were first wrapped with O-carboxymethyl chitosan to develop an upconversion rianoplatform and then chemically conjugated with the photosensitizer pyropheophorbide-a (Ppa) and RGD peptide c(RGDyK). The nanoparticle exhibited low dark toxicity and high biocompatibility. When injected into the tail vein of tumor-bearing U87-MG mice, UCNP-Ppa-RGD revealed an enhanced tumor-specific biodistribution and successful therapeutic effect following near-infrared laser irradiation. It possessed a significantly deeper therapeutic depth compared with conventional visible light triggered PDT using Ppa. The results suggest that the nanoplatform has advantages in the spectral application, and the constructed tumor-specific nanoparticle shows high clinical potential to serve not only as a photodynamic imaging reagent but also as a therapeutic agent for the treatment of large or deeply seated tumors. PMID- 26554159 TI - Folate-Modified Lipoplexes Delivering the Interleukin-12 Gene for Targeting Colon Cancer Immunogene Therapy. AB - The incidence and mortality rate of colorectal cancer increase every year, making it a serious threat to human health. Targeted immunogene therapy is a novel method of treating this type of cancer. Colon cancer overexpresses folate receptor alpha (FRalpha) and folate-modified liposomes for colon cancer immunogene therapy may suppress tumor growth effectively. In this study, F PLP/pIL12, an FRalpha-targeted lipoplex loading plasmid interleukin-12 (pIL12) was prepared and its physicochemical properties were characterized. Then the antitumor effect of F-PLP/pIL12 was studied in an in vivo model of CT-26 colon cancer. F-PLP/pIL12 was associated with about 56.6% tumor growth inhibition compared with the saline control. The production of malignant ascites was significantly less pronounced than in controls, and there were fewer tumor nodules and less overall tumor mass (P < 0.01). There was more IL12 expression and IFN-gamma secretion in F-PLP/pIL12-treated tumor tissues, but there was less FRalpha expression. The antitumor mechanisms involved inducing tumor cell apoptosis, reducing microvessel density, and stimulating TNF-alpha secretion. In addition, there were fewer M2 macrophages in the tumor microenvironment of tissues stimulated with F-PLP/pIL12, which also activated the natural killer cells. H&E staining of vital organs suggested that F-PLP/pIL12 is safe for use in intraperitoneally administered cancer therapy. It was here concluded that F PLP/plL12 may be a suitable targeting formulation for colon cancer immunogene therapy. PMID- 26554160 TI - Monolayer Graphene-Directed Growth and Neuronal Differentiation of Mesenchymal Stem Cells. AB - The development of an efficient platform for the growth and neuronal differentiation of stem cells is crucial for autologous cell therapy and tissue engineering to treat various neuronal disorders and neurodegenerative diseases. In this study, we describe the use of highly uniform graphene platforms that provide unique environments where unusual three-dimensional spheroids of human mesenchymal stem cells (hMSCs) are formed, which is advantageous for the differentiation of hMSCs into neurons. We suppose that graphene regulates the interactions at cell-substrate or cell-cell interfaces, consequently promoting the neurogenesis of hMSCs as well as the outgrowth of neurites, which was evidenced by the graphene-induced upregulation of early neurogenesis-related genes. We also demonstrated that the differentiated neurons from hMSCs on graphene are notably sensitive to external ion stimulation, and their neuronal properties can be maintained even after detaching and re-seeding onto a normal cell culture substrate, suggesting the enhanced maturity of resulting neuronal cells. Thus, we conclude that monolayer graphene is capable of regulating the growth and neural differentiation of hMSCs, which would provide new insight and strategy not only for autologous stem cell therapy but for tissue engineering and regenerative medicine based on graphene scaffolds. PMID- 26554161 TI - Cellular Uptake and Cytotoxic Effect of Epidermal Growth Factor Receptor Targeted and Plitidepsin Loaded Co-Polymeric Polymersomes on Colorectal Cancer Cell Lines. AB - Encapsulating chemotherapy drugs in targeted nanodelivery systems is one of the most promising approaches to tackle cancer disease, avoiding side effects of common treatment. In the last decade, several nanocarriers with different nature have been tested, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as their low toxicity. In this work, we synthesized, characterized and evaluated poly(trimethylene carbonate)-bock-poly(L-glutamic acid) derived polymersomes, targeted to epidermal growth factor receptor (EGFR), loaded with plitidepsin and ultimately tested in HT29 and LS174T colorectal cancer cell lines for specificity and efficacy. Furthermore, morphology, physico-chemical properties and plitidepsin loading were carefully investigated. A thorough in vitro cytotoxicity analysis of the unloaded polymersomes was carried out for biocompatibility check, studying viability, cell membrane asymmetry and reactive oxygen species levels. Those cytotoxicity assays showed good biocompatibility for plitidepsin-unloaded polymersomes. Cellular uptake and cytotoxic effect of EGFR targeted and plitidepsin loaded polymersome indicated that colorectal cancer cell lines were.more sensitive to anti-EGFR-drug-loaded than untargeted drug-loaded polymersomes. Also, in both cell lines, the use of untargeted polymersomes greatly reduced plitidepsin cytotoxicity as well as the cellular uptake, indicating that the use of this targeted nanocarrier is a promising approach to tackle colorectal cancer disease and avoid the undesired effects of the usual treatment. Furthermore, in vivo assays support the in vitro conclusions that EGFR targeted polymersomes could be a good drug delivery system. This work provides a proof of concept for the use of encapsulated targeted drugs as future therapeutic treatments for cancer. PMID- 26554162 TI - A Nonenzymatic Electrochemical Immunosensor for Ultrasensitive Detection of Tumor Biomarkers Based on Palladium Nanoparticles Conjugated Reduced Graphene Nanosheets. AB - A nonenzymatic electrochemical immunosensor based on palladium nanoparticles conjugated reduced graphene nanosheets (Pd-GS) for sensitive detection of cancer biomarker a-fetoprotein (AFP) is described. Primary antibody-AFP (Ab1) was immobilized onto the surface of reduced graphene nanosheets (rGO) through an amidation reaction between the carboxylic acid group of the rGO and the available amine groups of Ab1. Pd-GS which was prepared by one-spot synthesis is employed to immobilize secondary antibody (Ab2). The resulting Pd-GS-Ab2 conjugate was used as a label for the immunosensor to detect AFP. The amplified immunoassay exhibits high sensitivity, wide linear rang (0.01-10 ng/mL), low detection limit (3.0 pg/mL), acceptable stability and reproducibility. And such immunosensor also shows good recovery in the assay results for AFP in human serum samples. PMID- 26554163 TI - Genetic Variation of BCL2 (rs2279115), NEIL2 (rs804270), LTA (rs909253), PSCA (rs2294008) and PLCE1 (rs3765524, rs10509670) Genes and Their Correlation to Gastric Cancer Risk Based on Universal Tagged Arrays and Fe3O4 Magnetic Nanoparticles. AB - With the help of Fe3O4 nagnetic nanoparticles as a solid carrier and an excellent tool for separation, six SNP loci (rs2279115 of BCL2 gene, rs804270 of NEIL2 gene, rs909253 of LTA gene, rs2294008 of PSCA gene, rs3765524 and rs10509670 of PLCE1 gene) were selected to evaluate their relation to gastric cancer risk. Using two kinds of functionalized magnetic nanoparticles and universal tagged arrays, the whole operation procedure including genome DNA extraction and SNP genotyping was performed. All genotypes and allele frequencies were calculated in the cases and controls respectively to analyze their association with gastric cancer risk. Totally 200 pathological samples and 134 normal control subjects were collected. The results demonstrated that four SNP loci (rs2279115, rs804270, rs909253 and rs3765524) showed a potential association with gastric cancer risk, and the other two (rs2294008, rs10509670) possessed no difference/association among cases and controls. PMID- 26554164 TI - Gelatin Nanofiber Matrices Derived from Schiff Base Derivative for Tissue Engineering Applications. AB - Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)--a novel gelatin Schiff base derivative--and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08 +/- 1.5 MPa and 27.61 +/- 4.3 MPa, respectively while the modified gelatin and their blends showed 15.63 +/- 2.8 MPa and 24.47 +/- 8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm(-1) disappeared following exposure to UV light indicating the regeneration of free NH2 group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength. PMID- 26554166 TI - Preparing Your Team. PMID- 26554165 TI - Expanding Scope. PMID- 26554167 TI - Case Study: Christian Hospital EMS Community Health Access Program. PMID- 26554168 TI - Becoming Clinically Competent. PMID- 26554170 TI - The 6 rights. PMID- 26554169 TI - Case Study: Community Healthcare Emergency Collaborative's standardized MIH-CP curriculum. PMID- 26554171 TI - Synergistic, Not Competitive. PMID- 26554172 TI - TOP 10 POINTS for MIH-CP Success. PMID- 26554173 TI - EMS TIME MACHINE. PMID- 26554174 TI - A 'WICKED PROBLEM'. PMID- 26554175 TI - HYPEREMESIS. PMID- 26554176 TI - UNUSUAL OVERDOSE. PMID- 26554177 TI - REDS & BLACKS. PMID- 26554178 TI - Hanging from the balconies. PMID- 26554179 TI - Runway disaster readiness. PMID- 26554180 TI - Insulin pump therapy. PMID- 26554181 TI - HOT WAX. AB - High-potency marijuana wax smoked via dabbing is a newly encountered phenomenon with relevance to prehospital care providers and emergency physicians.The extract is only recently described in current peer-reviewed literature. The drug may produce paranoia and psychosis and mimic psychiatric problems. The synthetic process for this drug poses a risk for both fire and explosions creating burns and blast injuries. These four cases were encountered in a single ED in Los Angeles in a three-week period, suggesting this could be the tip of an emerging public health problem. All four of these patients were complex cases requiring advanced imaging and ICU care. Emergency personnel need to appreciate this new trend and the implications for pre-hospital care, disposition and ED treatment of these patients. PMID- 26554182 TI - PREPARATION THROUGH SIMULATION. PMID- 26554183 TI - MEETING EMERGING NEEDS. PMID- 26554184 TI - One pill can kill. PMID- 26554185 TI - Re-emerging infectious diseases. PMID- 26554186 TI - SHORTER SHIFTS. PMID- 26554187 TI - THE UPS & DOWNS OF EMS. PMID- 26554188 TI - Dear health secretary, you can end the waits. PMID- 26554189 TI - PEER SUPPORT CAN ENCOURAGE SELF-MANAGEMENT. PMID- 26554190 TI - BUILD A CLEARER WORKFORCE DATASET. PMID- 26554192 TI - RISING STARS: PATIENT INVOLVEMENT. A PROMISE TO SELF CARE. PMID- 26554191 TI - RISING STARS: LEADERSHIP. UNITED BY A DESIRE FOR CHANGE. PMID- 26554193 TI - RISING STARS: WORKFORCE. TIME TO BREATHE. PMID- 26554194 TI - THE MEDICO-SCIENTIFIC MARGINALISATION OF HOMEOPATHY: INTERNATIONAL LEGAL AND REGULATORY DEVELOPMENTS. AB - The 2010 report of the United Kingdom Science and Technology Committee of the House of Commons and the 2015 report of the Australian National Health and Medical Research Council have overtaken in significance the uncritical Swiss report of 2012 and have gone a long way to changing the environment of tolerance toward proselytising claims of efficacy in respect of homeopathy. The inquiry being undertaken in the United States by the Food and Drug Administration during 2015 may accelerate this trend. An outcome of the reports and inquiries has been a series of decisions from advertising regulators and by courts rejecting medically unjustifiable claims in respect of the efficacy of homeopathy. Class actions have also been initiated in North America against manufacturers of homeopathic products. The changing legal and regulatory environment is generating an increasingly scientifically marginalised existence for homeopathy. That new environment is starting to provide effective inhibition of assertions on behalf of homeopathy and other health modalities whose claims to therapeutic efficacy cannot be justified by reference to the principles of evidence-based health care. This has the potential to reduce the financial support that is provided by insurers and governments toward homeopathy and to result in serious liability exposure for practitioners, manufacturers and those who purvey homeopathic products, potentially including pharmacists. In addition, it may give a fillip to a form of regulation of homeopaths if law reform to regulate unregistered health practitioners gathers momentum, as is taking place in Australia. PMID- 26554195 TI - DISCIPLINARY PROCEEDINGS AGAINST DOCTORS WHO ABUSE CONTROLLED SUBSTANCES. AB - This study examined 27 reports from disciplinary tribunals throughout Australia (save Tasmania where reports were not accessible) against medical practitioners who abused narcotic analgesics (often combined with other drugs of addiction) between 2010 and 2015. The reports revealed that 12 medical practitioners were in their 40s; five in their 30s; and one person still in their 20s. Although the majority were general practitioners (15 out of 27), other medical specialties were also represented. Self-administered pethidine was the most prevalent opioid (11 out of 27) and was the only drug used alone. Morphine was self-administered by six doctors; the same number used high doses of Panadeine Forte, codeine and codeine phosphate. Fentanyl was abused by five doctors. Surprisingly, fewer medical practitioners appear to use propofol, and similar opiates such as tramadol (Tramol) and/or oxycodone (Endone). The examination of cases suggests lack of consistency in the imposition of professional sanctions and penalties by the relevant tribunals. To remedy this problem, it is suggested that disciplinary tribunals should apply the test of proportionality in the form of "reasonable necessity" when deciding whether to remove or suspend the addicted medical practitioner from the Register. PMID- 26554196 TI - METHAMPHETAMINE: WHERE WILL THE STAMPEDE TAKE US? AB - Methamphetamine, particularly "ice", currently preoccupies the media and there are a range of government initiatives which seem to follow media interest. We summarise the progress of government attention, briefly review health concerns associated with methamphetamine use, and summarise the evidence for treatments, including psychosocial interventions and medications. Amid concerns that governments will seek to fund any promising initiative in order to be perceived as responding to an epidemic, we caution that existing treatments should not be abandoned in favour of untested but potentially attractive treatments. Harm reduction and outpatient psychological treatments remain the mainstay of drug treatment programs and may be more cost-effective and broader-reaching than inpatient, medication-based detoxifications. PMID- 26554197 TI - "NEVER REGARD YOURSELF AS ALREADY SO THOROUGHLY INFORMED": THE WITHDRAWAL OF ITS INVITATION TO RODNEY SYME TO ADDRESS ITS 2015 CONGRESS BY THE ROYAL AUSTRALASIAN COLLEGE OF PHYSICIANS. AB - In 1628, William Harvey presented his revolutionary theory of the circulation to ears at the Royal College of Physicians that had been deafened by the unquestionable authority of Galen's teachings, from one and a half millennia in the past. Harvey's theory was initially rejected, despite his faith in his colleagues being eager for truth and knowledge, and never regarding themselves as so well informed that they would not welcome "further information". Recently Rodney Syme, the retired Melbourne urologist who for a long time has agitated for the legalisation of assisted dying, and also challenged the authorities to apply the current law in response to his admitted assistance to a number of individuals, was invited to address the 2015 Congress of the Royal Australasian College of Physicians. At the eleventh hour, the invitation to speak was withdrawn. In this column, we trace the course of events leading to this withdrawal of the invitation, and describe some of the correspondence to and from the College in response to the withdrawal. We draw parallels between the experiences of Harvey and Syme, and point to lessons to be learnt from the recent episode of apparent unwillingness, on the part of an institution that seeks to present itself as outward-looking, progressive and socially aware, to fulfil this promise in the increasingly important area of the end-of-life. PMID- 26554198 TI - AUSTRALIAN COMPETITION AND CONSUMER COMMISSION v ACN 117 372 915: SHOULD CONSUMER LAW REGULATE DOCTOR-PATIENT RELATIONS IN A CORPORATISED HEALTH CARE SYSTEM? AB - In April 2015, North J of the Federal Court of Australia made a finding of unconscionable conduct against Advanced Medical Institute, a promoter and provider of erectile dysfunction treatment, in a case concerning unfair contract terms (Australian Competition and Consumer Commission vACN 117 372 915 Pty Ltd (in liq) (formerly Advanced Medical Institute Pty Ltd) [2015] FCA 368). The contract required a minimum 12-month commitment, with costs exceeding treatments available from general practitioners, and made refunds available only after all possible treatment plans were exhausted which included penile injections. This column analyses that case, particularly in respect to the consumer law standards of practice under which it was litigated. Those standards refer to patients as "consumers" yet North J made extensive reference to the Good Medical Practice: A Code of Conduct for Doctors in Australia, a text which refers to "patients", as evidence of what constitutes appropriate professional conduct or practice for the health profession. This column considers whether legislative and judicial categorisation of patients (a class of people presumptively suffering, sick and vulnerable) as "consumers" undermines the formal and informal protections accorded to patients under normative systems of medical ethics such as those represented by the Code. The case, it is argued, also illuminates the contemporary tensions between the ethical, legal and human rights standards required of doctors in their treatment of patients and the commercial interests of businesses. PMID- 26554199 TI - FURTHER ARGUMENTS FOR UNIFORM MEDICINES LEGISLATION. PMID- 26554200 TI - Medical teams and the standard of care in negligence. AB - Medical teams are essential to the delivery of modern, patient-centred health care in hospitals. A collective model of responsibility envisaged by team care is inconsistent with common law tort liability which focuses on the individual rather than the team. There is no basis upon which a team can be liable as a collective at common law. Nor does the common law'countenance liability for the conduct of other team members absent some form of agency, vicarious liability or non-delegable duty. Despite the barriers to the adoption of a team standard of care in negligence, there is scope for team factors to have a role in determining the standard of care so that being a team player is part and parcel of what it is to be a competent professional. If this is the case, the skill set, and the standard of care expected of the individual professional, includes skills based on team models of communication, cross-monitoring and trust. PMID- 26554201 TI - Prevention of non-communicable diseases in Australia: What role should public health law play? AB - This article explores the role of public health law in the prevention of non communicable diseases in Australia. The growing urgency to address these diseases is acknowledged and the definition of public health law explored. It is argued that a broad definition of public health law would allow greater recognition of the numerous ways that law can positively influence health outcomes at the population level. Far from substantiating claims of over-reaching state intervention, public health law in the 21st century in Australia should be viewed as a more nuanced and protective strategy in promoting better public health. Adopting this approach offers a way forward towards addressing rising rates of non-communicable diseases, as well as significant health inequities, but it will require greater political will and leadership. PMID- 26554202 TI - Personal responsibility or shared responsibility: What is the appropriate role of the law in obesity prevention? AB - Sensitive to allegations of "nanny state" paternalism, Australian governments support the doctrine that combating obesity is a matter of personal responsibility. Policy-makers endorse the "holistic" approach to obesity prevention, with a view to managing both sides of the nutritional energy equation. This paradigm allows the food and drinks industry to deflect its contributory responsibility for the epidemic and to avoid more stringent regulatory intervention beyond existing self-regulatory and corporate social responsibility regimes. This article argues that the industry must bear shared responsibility for the extent of the obesity crisis, although it cannot bear sole responsibility It defends the public interest case for more invasive, government led regulation, reframing the crisis as one of public not individual burdens. Mindful of the political risk associated with unfocused calls for regulatory intervention, it articulates a set of regulatory principles to ensure that the interests of consumers and industry are properly acknowledged prior to further regulatory intervention. Finally, the article clarifies the subject, object and content of possible regulatory initiatives, offering an evaluation of their efficacy, practicality and fairness. PMID- 26554203 TI - Assessing testamentary and decision-making capacity: Approaches and models. AB - The need for better and more accurate assessments of testamentary and decision making capacity grows as Australian society ages and incidences of mentally disabling conditions increase. Capacity is a legal determination, but one on which medical opinion is increasingly being sought. The difficulties inherent within capacity assessments are exacerbated by the ad hoc approaches adopted by legal and medical professionals based on individual knowledge and skill, as well as the numerous assessment paradigms that exist. This can negatively affect the quality of assessments, and results in confusion as to the best way to assess capacity. This article begins by assessing the nature of capacity. The most common general assessment models used in Australia are then discussed, as are the practical challenges associated with capacity assessment. The article concludes by suggesting a way forward to satisfactorily assess legal capacity given the significant ramifications of getting it wrong. PMID- 26554204 TI - Slice them up or slice them out? Legal liability for operating on the troublesome patient in cosmetic surgery. AB - The practice of cosmetic surgery is constructed as psychologically beneficial. This therapeutic promise transforms cosmetic surgery into proper medical treatment. However, there is emerging evidence that a significant percentage of cosmetic surgery patients suffer from the condition of Body Dysmorphic Disorder (BDD), which is characterised by excessive preoccupation with imagined or minor defects in appearance. BDD is uniformly identified as a strong contra-indication for cosmetic surgery. Articles in scholarly journals on cosmetic surgery identify the "red flag" indicators to assist in screening out problem patients. However, a close examination of the most common indicators reveals that most are ineffective in identifying BDD in prospective patients. This article also considers the legal liability of cosmetic surgeons who operate on patients with BDD, and concludes that there is little likelihood of liability in trespass or negligence under current Australia law. PMID- 26554205 TI - State intervention in pregnancy: Should the law respond thus to the problem of Foetal Alcohol Spectrum Disorder? AB - Maternal consumption of alcohol during pregnancy poses a serious threat to the life and health of unborn children. A submission to the Queensland Child Protection Commission of Inquiry proposed that the State's Child Protection Act be extended to allow intervention to protect unborn children, with a court empowered to order that the mother be taken into care pending birth, or otherwise impose conditions upon conduct. This article considers whether or not the law in Australia should respond to the problem of Foetal Alcohol Spectrum Disorder by allowing the involuntary treatment and detention of pregnant women. The focus, is upon intervention in response to existing pregnancies. Using a utilitarian critical framework, this article evaluates the merits of creating powers to compel treatment and detain in light of current legal principles relating to maternal autonomy and the legal position of the foetus. The common law position is considered, as well as current legislation allowing intervention in autonomous decision-making and whether or not these statutes may be enlivened to prevent foetal harm. This article suggests that permitting involuntary treatment and detention would be a significant policy change. It weighs up benefits and potential harms in considering whether or not such action would result in the most "good". PMID- 26554206 TI - Criminal injuries compensation: Protecting vulnerable applicants. AB - Each year large numbers of persons sustain injury as a consequence of criminal behaviour. All Australian jurisdictions provide State-funded compensation to those harmed in this way. In the case of vulnerable applicants, the Assessor must consider not simply the appropriate and fair amount of compensation, but also how a person will be affected by the payment of compensation. Often a vulnerable applicant will apply through a guardian or a public trustee, although many apply in person. This article examines the use of legislative provisions, rules, regulations and practices in the various Australian jurisdictions in relation to how vulnerable applicants may be protected and supported once an award of compensation is made in their favour. Most jurisdictions provide for a mechanism by which compensation may be held in trust where the Assessor considers that the applicant may be unable to manage his or her financial affairs in his or her best interests. This article explores what factors are taken into account by Assessors in the absence of and pursuant to legislative directions. It considers how the approach may vary across jurisdictions and creative approaches to financial protection of vulnerable applicants. PMID- 26554207 TI - Unwanted pregnancy: The outer boundary of "treatment injury" in the New Zealand accident compensation scheme. AB - The New Zealand accident compensation scheme has undergone many changes over the years and these changes are reflected in the way unwanted pregnancy claims have been dealt with under the regime. The New Zealand Supreme Court has now confirmed that pregnancy as a result of medical misadventure can be classified as a personal injury under the scheme with the result that the woman patient is entitled to the benefits of the scheme and may not pursue a common law claim against the medical practitioner. This article analyses two recent decisions in the context of consideration of the changing fortunes of the unwanted pregnancy claims. PMID- 26554208 TI - Patient's right to information under the New Zealand Code of Rights. AB - The Code of Health and Disability Services Consumers' Rights includes right 6: the "Right to be Fully Informed". Analysis of the Health and Disability Commissioners' opinions between 2008 and 2013 that have discussed right 6 shows that the duties on providers have increased in a number of areas: the need to inform of risks, including provider-inherent risks; open disclosure of adverse events; ongoing need to inform consumers throughout the therapeutic relationship; information of all available options; and provision of sufficient time between disclosure of information and obtaining informed consent for provision of health services. Following a breach opinion, the Human Rights Review Tribunal and the Health Practitioners Competency Tribunal, on occasion, have the opportunity to consider the case but their role in law development is limited compared with that of the Commissioner. The limitations of law development in this manner are discussed. PMID- 26554209 TI - A way through the dark and thorny thickets? The adjudication of "serious injury" under the narrative tests in the Transport Accident Act 1986 (Vic) and the Workplace Injury Rehabilitation and Compensation Act 2013 (Vic). AB - The so-called "narrative" test provides the means by which injured persons who satisfy the statutory and common law definition of "serious injury" may bring proceedings for common law damages under s 93 of the Transport Accident Act 1986 (Vic) and s 134AB of the Accident Compensation Act 1985 (Vic) (or, for injuries after 1 July 2014, under ss 324-347 of the Workplace Injury Rehabilitation and Compensation Act 2013 (Vic)). These are among the most litigated provisions in Australia. This article outlines the legislative and political background to these provisions, the provisions themselves, and an account of the statutory and common law requirements needed to satisfy the provisions. PMID- 26554210 TI - Victim Tracking at a Major Incident. A fire ravages a family--what's the best way to keep the patients straight? PMID- 26554211 TI - Be a Leader, Not a Friend. Failing to deal with employee problems head-on is a recipe for disaster. PMID- 26554212 TI - Considerations of a Rural CP Program. What goes into operating outside the urban environment? PMID- 26554213 TI - Just-in-Time Stock Control. A well organized logistics system keeps your agency moving and equipped. PMID- 26554214 TI - How to Conduct the Patient Interview. Communicating successfully with patients requires strategy, flexibility and practice. AB - As community paramedicine and other nonemergent initiatives become commonplace in EMS, caregivers are going to need communication skills that go beyond SAMPLE checklists. A minimalist approach to dialogue with patients, considered preferred if not essential in what was once almost exclusively a light-and-sirens environment, isn't acceptable when prehospital interventions require a thorough understanding not only of chief complaints, but also how the physical part of illness and injury is framed by the patient's environment. Be considerate, be as thorough as time permits, and pay attention! Next time we'll talk about interviewing prospective employees. PMID- 26554215 TI - Alternative Airways: The Who, What, Where, When and How. PMID- 26554216 TI - Taking the Fear Out of RSI/DSI. PMID- 26554217 TI - Letting the Days Go By. How a background in EMS fostered a successful marriage. PMID- 26554218 TI - [Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from 8 Hospitals in Chiba Prefecture Following the Introduction of 7-valent Pneumococcal Conjugate Vaccine]. AB - We investigated the susceptibility of Streptococcus pneumoniae isolated from 8 hospitals in Chiba prefecture during 2012-2013. We further checked the serotype of S. pneumoniae derived from invasive pneumococcal disease (IPD). We tested for antimicrobial susceptibility in 256 clinical isolates (137 isolates from children, 119 isolates from adults) for 25 drugs. In MIC50 and MIC90, there were very little differences between children and adults, but there were 3 isolates from adults which were resistant to levofloxacin. The most major serotypes were 15A and 3 in IPD. Additionally there was no isolation of the type contained in the 7-valent pneumococcal conjugate vaccine in children, so it seems that the vaccination is very effective for children. Furthermore, in contrast with our preceding report, a decreasing was seen in PCG resistant proportion of S. pneumoniae. The maximum PCG-MIC was 2 MUg/mL. PMID- 26554219 TI - [Molecular Detection Methods for Vibrio parahaemolyticus in Seafood]. AB - To detect Vibrio parahaemolyticus in seafood, we evaluated efficient combinations of molecular methods with DNA extraction methods using heat extraction and alkaline heat extraction, and PCR, real-time PCR and loop-mediated isothermal amplification (LAMP) assays were performed targeting V parahaemolyticus species specific genes (tlh and rpoD) and pathogenic factors genes (tdh and trh). The species-specific genes were detected in all combinations of two strains (a tdh * trh1-positive strain and a trh2-positive strain), two kinds of shellfish (oyster and bloody clams) and molecular methods with tlh-real time PCR or rpoD-LAMP assays with DNA of alkaline heat extraction at 85-145cfu/test level. tdh was detected in both seafoods with real time PCR assay with DNA of heat extraction at 85cfu/test level, and detected with the LAMP and real time PCR assays with DNA of alkaline heat extraction at 85cfu/test level. Detection of both trh1 and trh2 with the PCR assay with DNA of alkaline heat extraction was comparatively high though trh2 was detected with the LAMP assay with DNA of alkaline heat extraction at 145cfu/test level. It, however, is necessary to investigate more sensitive trh detection methods. In this study, the results indicated that tlh-real time PCR or rpoD-LAMP, tdh-real time PCR and tdh-LAMP assays with DNA of alkaline heat extraction are relatively-sensitive methods to detect V. parahaemolyticus in seafood. PMID- 26554220 TI - [Effect of Human Serum Albumin on Endotoxin Scattering Photometry]. AB - PURPOSE: Laser scattering photometry (ESP) is a newly developed plasma endotoxin assay method using horseshoe crab amebocyte lysate (AL) that recognizes small particles produced by polymerization of coagulin under the stirring conditions at 1000rpm. We elucidated the effect of human serum album (HSA) in the ESP method. METHODS: AL was dissolved with 630MUL of the specimen and a 200-MUL aliquot was used for ESP; this conventional protocol was regarded as the ESP630 method. The ESP210 method was also used, i. e. AL was dissolved with 210MUL of the specimen and a 200-MUL aliquot was used for ESP. RESULTS: Water induced the agglutination, and HSA prolonged the agglutination time depending on its concentration especially in the ESP630 method. The water-induced agglutination was not inhibited by the addition of anti-factor C monoclonal antibody, and amidinophenyl benzoate hydrochloride, used as a clotting enzyme inhibitor, intensively inhibited the water-induced agglutination. Therefore, the water-induced agglutination was suggested to be a false-positive reaction to non-specific activation of the clotting enzyme. The HSA-induced prolongation of the reaction in the national health insurance-covered turbidimetric kinetic assay was not observed. CONCLUSION: HSA or plasma protein seemed to affect the result, especially in the ESP630 method, and a non-specific reaction was found to occur in the ESP methods. PMID- 26554221 TI - [A Study on the Clinical Course and Antimicrobial Susceptibility of Mycoplasma pneumoniae in a Community Hospital]. AB - Recently, reports of macrolide-resistant strains of Mycoplasma pneumoniae have been increasing. We examined the antimicrobial susceptibility and clinical significance in patients with M. pneumoniae. Seventy patients in whom M. pneumoniae was detected from 2008 to 2012 were included in the study, and compared with patients between 2003 and 2006. There were no macrolide-resistant strains detected in the 38 strains from 2003 to 2006, but from 2008 to 2012, out of the 70 strains 46 (65.7%) were positive for the macrolide-resistant 23SrRNA gene mutant (A2063G), which is consistent with recent trends. Comparison between cases of macrolide resistant strains and those with macrolide sensitive strains did not reveal a significant difference in the hospitalization period. The approximate duration of fever was 7 days; for both cases: those who received effective antimicrobials as the initial therapy, and for those with macrolide sensitive strains. It seems that the duration of fever depends on susceptibility to the initial antimicrobials regardless of macrolide resistance. There were some patients that improved without use of quinolone or minocycline, though macrolide resistant strains were detected. These patients did not reveal extension of the hospital stay nor aggravation of pneumonia. This suggests that a macrolide drug might be the first choice drug for M. pneumoniae even now, and a change of drug should be considered when fever duration is long. PMID- 26554222 TI - [A Case of Clinically Mild Encephalitis/encephalopathy with a Reversible Splenial Lesion due to Dengue Fever]. AB - Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48 year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS. PMID- 26554223 TI - [Pulmonary Nocardiosis due to Nocardia asiatica in a Patient with ANCA-associated Vasculitis]. AB - Nocardia asiatica is a rare causative organism responsible for opportunistic infection, and was first reported by Kageyama et al. in 2004. We report herein on a very rare case of N. asiatica infection in a 76-year old male patient with ANCA associated vasculitis and a history of pulmonary tuberculosis. The patient developed pulmonary nocardiosis due to N. asiatica while receiving glucocorticoid therapy. Chest computed tomography demonstrated multiple granules and cavity formation mainly in the left lower lobe. From the images, we suspected opportunistic infection, possibly pulmonary tuberculosis or pulmonary damage due to ANCA-associated vasculitis. Nocardia sp. was detected from a bronchoalveolar lavage culture and N. asiatica was identified by 16S ribosomal DNA gene sequencing. Cranial magnetic resonance imaging revealed no abnormality. Administration of Doripenem (1.5g/day) and sulfamethoxazole-trimethoprim (4g/day) was started, and the patient's clinical and imaging findings promptly improved. Thereafter, he received sulfamethoxazole-trimethoprim (2g/day) and prednisolone (10 mg/day) as maintenance therapy for ANCA-associated vasculitis for more than one year, and there has since been no recurrence of the Nocardia infection. PMID- 26554224 TI - [A Case of Osteomyelitis with a Granulomatous Lesion Caused by Salmonella Infantis]. AB - We report herein on a case of osteomyelitis with a granulomatous lesion caused by Salmonella enterica subsp. enterica serovar Infantis (Salmonella Infantis). A 30 year-old Japanese man presenting with a 3-week history of left ankle pain was suspected to have either a tumor or osteomyelitis, on the basis of imaging study findings. He underwent a surgical resection of the lesion. Histopathological examination revealed a granuloma. However, S. Infantis was cultured from the biopsy sample. Cefazolin was initially administered as empirical therapy. We switched the antibiotic to ampicillin on the basis of the anitibiotic susceptibility test results. Six weeks after intravenous ampicillin therapy, we switched to oral ciprofloxacin. He has had no recurrence in the 3 years after treatment completion. Salmonella osteomyelitis is rare and this pathogen seldom causes a granulomatous lesion. According to the findings in our case, Salmonella spp. should be considered as one of the differential diagnoses for granulomatous lesions in the bone. PMID- 26554225 TI - [Bilateral Granulomatous Renal Masses after Intravesical BCG Therapy for Non muscle-invasive Bladder Cancer and Carcinoma in Situ of the Upper Urinary Tract: A Case Study]. AB - Bacillus Calmette-Guerin (BCG) is commonly used not only as an infant vaccination, but also as a treatment of and prophylaxis to prevent recurrence in the management of non-muscle-invasive bladder cancer. However, the use of "live" BCG is sometimes complicated by associated infection. We present a case study of a 77-year-old man who developed bilateral renal masses after intravesical BCG therapy was initiated in November 2013, following transurethral resection of non muscle-invasive bladder cancer. After four courses of BCG (Japan strain, 80 mg per treatment) instillations, a computed tomography examination for febrile episodes showed multiple bilateral renal masses, accompanied by a histological finding of a granulomatous reaction. An acid fast bacterium was cultured from only urine among blood, urine, and microscopic samples. Using the cultured strain, BCG infection was confirmed by the specific gene deletion pattern based on allele-specific polymerase chain reaction analysis. Anti-tuberculosis treatment, including isoniazid (300 mg/day), rifampicin (600 mg/day), and ethambutol (1,000 mg/day), was started for the BCG-related renal granuloma in February 2014. After 3 months, antibiotic therapy was discontinued owing to severe appetite loss, though the masses remained solid. No rapid growth has been detected after anti-BCG therapy. Intravesical BCG therapy is recommended worldwide as one of standard treatments for non-muscle-invasive bladder cancer. We should closely observe patients undergoing this approach for emerging BCG complications. PMID- 26554226 TI - [Concern Regarding a Mumps Epidemic Through Antibody Screening in College Students]. PMID- 26554227 TI - [A 1-year-old Girl in Whom Nontypeable Haemophilus influenzae was Isolated from Her Blood After Completion of H. influenzae Type b Vaccine--Importance of Serotyping of Invasive of H. influenzae Strain]. PMID- 26554228 TI - [Clinical Manifestations of Japanese Spotted Fever: Multi-institution Study in Endemic Areas in Japan]. PMID- 26554229 TI - Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus. AB - BACKGROUND: This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element binding protein (CREB) in the auditory cortex of rats with tinnitus. METHODS: Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. RESULTS: Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. CONCLUSIONS: These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus. PMID- 26554230 TI - Total Adiponectin, Adipocyte Fatty Acid Binding Protein, Fibroblast Growth Factor 21 and Proinflammatory Marker Levels During the Early Stage of Acute Pancreatitis -A Pilot Study. AB - BACKGROUND: Recently, an increasing interest has been extended to the secretory products of fat tissue adipokines and their role in the course of acute pancreatitis (AP). The study aimed to evaluate the levels of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP), fibroblast growth factor (FGF 21), and selected proinflammatory markers during the early stage of acute pancreatitis. The parameters were measured for identification of the patients with the high risk of severe AP. METHODS: 84 subjects (47 males, 37 females) with AP were divided into the subgroups according to body mass index (BMI), disease severity score (mild AP vs. severe AP) and computer tomography severity index score (CTSI A vs. CTSI B vs. CTSI C). All laboratory examinations were determined on day 1 and day 4 after admission. Adipokines were analyzed using the ELISA kit methods. RESULTS: No significant variance was found in adipokine levels between subjects with mild and severe AP, but C-reactive protein (CRP) and interleukin 6 (IL-6) were significantly elevated in patients with severe AP on day 4 (CRP medians: 209.8 mg/L vs. 51.2 mg/L, p < 0.000; IL-6 medians: 79.5 ng/L vs. 25.9 ng/L, p < 0.01). FGF 21 medians were distinctly higher on day 1 in all observed subgroups compared to day 4 (mild AP: 669.9 ng/L vs. 261.7 ng/L; severe AP: 619.4 ng/L vs. 468.0 ng/L; CTSI A: 631.4 ng/L vs. 246.2 ng/L; CTSI B: 2226.3 ng/L vs. 693.1 ng/L; CTSI C: 572.6 ng/L vs. 310.8 ng/L). Similarly, this phenomenon was found for A-FABP and IL-6 as well. A-FABP and FGF 21 levels decreased during the first four days together, but independently of the IL-6 decline, regardless of AP severity. CONCLUSIONS: Elevated levels of CRP and IL-6 in subjects with severe form of AP on day 4 indicate a diagnostic utility of both parameters in the disease severity prediction. Increased FGF 21 at admission compared to day 4 suggests its potential role as an immediate response gene during pancreatic injury. The dynamics of FGF 21 and A-FABP levels probably reflect the improvement of clinical condition in the early stage of AP. PMID- 26554231 TI - Circulating MicroRNAs as Promising Biomarkers in Forensic Body Fluids Identification. AB - In the last 20 years, DNA molecular analysis has become an important tool in forensic investigations. Currently, it is possible to genotype all types of biological traces or micro-traces containing nucleated cells if they are not entirely destroyed, chemically or bacterial. The DNA profiling is based on the short tandem repeats (STR) and aids in human identification from biological samples, but due to the recent advances in molecular genetics, other biomarkers have been proposed to be used in forensic identifications, such as: messenger RNA(mRNA), microRNA (miRNA), and DNA methylation. MicroRNAs are part of a class of small, non-coding RNAs that contain 19 - 23 nucleotides. MicroRNAs play an important role in the regulation of biochemical mechanisms, cell proliferation and other cellular mechanisms in the human body. The level of microRNAs in blood and other body fluids (urine, saliva, sweat) increases as a consequence of altered pathophysiological mechanisms and tissue insult. Moreover, the stability and specificity of microRNAs make them ideal candidates for circulating biomarkers in forensic bioanalytical procedures. In this review, we want to present a brief overview of biogenesis, functions, and applications of miRNAs in the identification of forensic body fluids. PMID- 26554232 TI - Homocysteine in Chronic Heart Failure. AB - BACKGROUND: Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease. Homocysteine (Hcy) can generate reactive oxygen species. Oxidative stress enhances the progression of cardiovascular diseases and has long been implicated in chronic heart failure (CHF). This study was to evaluate the predictive value of plasma Hcy levels in CHF patients and to investigate the relationship with other markers. METHODS: We investigated 134 adult CHF patients (males, 74%; mean age, 60.0 +/- 14.8 years). Echocardiography, 6-min walk test, and determination of peak oxygen consumption (VO(2max)) were performed. Serum levels of Hcy and other markers were determined. Clinical follow-up was performed at five years. RESULTS: The mean Hcy level was markedly elevated in CHF patients (18.4 +/- 7.83 MUmol/L) vs. control subjects (12.8 +/- 3.14 MUmol/L; p < 0.01), whatever the etiology of heart failure (non-ischemic, n = 74, 17.6 +/- 7.8 MUmol/L; ischemic, n = 60, 19.3 +/- 7.8 MUmol/L). Hcy correlated negatively with VO(2max) and positively with BNP. Kaplan-Meier analysis showed that CHF patients with HHcy > 15 MUmol/L had a significantly lower survival rate (35% vs. 56%, log rank p < 0.05) than those without HHcy. Cox regression revealed that HHcy and hs CRP were the most powerful independent predictors of mortality in patients at 5 years. CONCLUSIONS: HHcy is common in CHF patients and is associated with an increased risk of death at 5 years. We suggest that Hcy can be used in clinical practice as an additional risk marker in CHF patients with various medications. PMID- 26554233 TI - Estimation of Aluminum, Arsenic, Lead and Nickel Status in the Samples of Different Cigarettes and their Effect on Human Health of Irish Smoker Hypertensive Consumers. AB - BACKGROUND: Cigarette smoking interferes with the metal homeostasis of the human body, which plays a crucial role for maintaining health. A significant flux of heavy metals, among other toxins, reaches the lungs through smoking. In the present study, the relationship between toxic element (TE) exposure via cigarette smoking and hypertension incidence in population living in Dublin, Ireland is investigated. METHODS: The toxic elements arsenic (As), aluminum (Al), nickel (Ni), and lead (Pb) were determined in biological (scalp hair and, blood) samples of patients diagnosed with hypertension who are smokers living in Dublin, Ireland. These results were compared with age- and sex-matched healthy, nonsmoker controls. The different brands of cigarettes (filler tobacco, filter, and ash) consumed by the studied population were also analyzed for As, Al, Ni, and Pb. The concentrations of TEs in biological samples and different components of the cigarettes were measured by inductively coupled plasma atomic emission spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked using certified reference materials. RESULTS: The recovery of all the studied elements was found to be in the range of 97.8% - 99.6% in certified reference materials. The filler tobacco of different branded cigarettes contains As, Al, Ni, and Pb concentrations in the ranges of 0.432 - 0.727 MUg, 360 - 496 MUg, 0.715 - 1.52 MUg, and 0.378 - 1.16 MUg/cigarette, respectively. The results of this study showed that the mean values of Al, As, Ni, and Pb were significantly higher in scalp hair and blood samples of hypertensive patients in relation to healthy controls, while the difference was significant in the case of smoker patients (p < 0.001). The levels of TEs were 2 - 3-fold higher in scalp hair and blood samples of non-hypertensive smoker subjects as compared to nonsmoker controls. CONCLUSIONS: The high exposure of toxic metals as a result of cigarette smoking may be synergistic with risk factors associated with hypertension. PMID- 26554234 TI - Serum Gamma-Glutamyltransferase and Ferritin are Related to Insulin Resistance: A Population-Based Study. AB - BACKGROUND: Recent studies have reported the association of gamma glutamyltransferase (GGT) or ferritin with metabolic disorders. However, there has been no large population-based study assessing the interrelationship of these two biomarkers and their association with insulin resistance. METHODS: A population-based cross-sectional study was carried out in the Chinese Liangshan Yi ethnic group. 756 eligible subjects, aged 20 - 74 years, were included. Demographic characteristics, medical history, and lifestyle data were collected through questionnaires. An oral glucose tolerance test was performed. Laboratory tests, including GGT and ferritin measurements, were conducted. Spearman's rank order correlation and multiple linear regression were used to calculate the correlation of GGT with ferritin and their relationship to the insulin resistance index determined by the homeostasis model assessment (HOMA-IR). RESULTS: A significant correlation between serum GGT and ferritin levels was found (r = 0.393, p < 0.05). GGT was independently correlated with ferritin after adjustment for age, gender, place of residence, education, income, leisure-time physical activity, drinking, smoking, body mass index, systolic pressure, diastolic pressure, hepatitis B surface antigen, anti-hepatitis C virus, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose, 2-hour postprandial plasma glucose, uric acid, and urinary albumin to creatinine ratio (p < 0.05). Positive correlations were established between HOMA-IR and GGT (standard beta = 0.252) or ferritin (standard beta = 0.181) after adjustment for multiple confounders (p < 0.05). CONCLUSIONS: Insulin resistance is associated with elevated serum GGT and ferritin. A combined determination of GGT and ferritin might lead to better predictions in patients with insulin resistance. PMID- 26554235 TI - Decreased Expression of Aquaporin-1 in Lung Tissue of Silicotic Rats. AB - BACKGROUND: Aquaporin-1 (AQP-1), found in the early 1990s, a water channel protein in the cell membranes of mammals, has been reported to play an important role in water balance of the respiratory system. However, there are a few studies about the role of AQP in occupational pulmonary disease such as silicosis. This study is to explore the information of aquaporin-1 (AQP-1) in the pathogenesis of silicosis by examining AQP expression, distribution, and location in the lung tissue of a silicotic rat model. METHODS: Male Wistar SPF rats were divided randomly into the following 8 groups (n = 8 per group): (1) saline control group: instillation of 1 mL sterile physiological saline; (2) silica groups (ld, 7d, 14d, 28d, 42d, 56d): instillation of a suspension of 50 mg silica dust in a total volume of 1 mL sterile physiological saline; (3) the normal control group without treatment. Immunohistochemistry, immunofluorescence, and western blot were used to detect distribution and expression of AQP-1 in the lung tissue of rats exposed to silica. RESULTS: The expression of AQP-1 between normal and the saline control rats showed no significant difference, but was decreased in the silicotic model rats' lung. CONCLUSIONS: The expression of AQP-1 decreased in silicotic rats, which suggests that AQP-1 may play an important role in the formation of silicosis. PMID- 26554236 TI - A Functional Single-Nucleotide Polymorphism in Pre-microRNA-196a2 is Associated with Atrial Fibrillation in Han Chinese. AB - BACKGROUND: MicroRNAs are small, single-stranded, non-protein-coding RNAs of about 22 nucleotides. MicroRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in the corresponding sequence space are likely to make a significant contribution to phenotypic variation. A T/C genetic variant (rs11614913) in the pre-miR-196a2 sequence could alter mature miR-196a expression and target mRNA binding. The aim of the present study is to evaluate the relationship between this polymorphism and atrial fibrillation (AF). METHODS: A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. Genotypes of the premiR-196a2 were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The distribution of the pre-miR-196a2 genotypes (TT, TC, and CC) was 15.38%, 46.15%, and 38.46% in the AF group and 39.66%, 46.55%, and 13.79% in the controls, respectively (p = 0.0011). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 3.968-fold increased risk of AF (adjusted OR = 3.968, 95% CI = 1.633 - 9.644, p = 0.002). AF patients with the TC+CC genotype had greater left atrial dimension than did patients with the TT genotype (42.10 +/- 8.74 vs. 35.13 +/- 8.16, p = 0.0224). CONCLUSIONS: Our data support that the pre-miR-196a2 polymorphism is associated with AF, and the C allele is a risk factor for AF. PMID- 26554237 TI - D-dimer, a Potential Marker for the Prediction of Severity of Acute Pancreatitis. AB - BACKGROUND: A number of experimental studies have been put forth suggesting an important role of the hemostatic system in acute pancreatitis (AP) in the recent past. However, meaningful studies on clinical values of parameters of the hemostatic system in predicting pancreatitis associated complications are still scarce. In the current investigation, we evaluated the role of D-dimer to predict the severity of acute pancreatitis on day 1 of admission to the hospital. METHODS: A total of 160 subjects (75 mild AP + 35 severe AP + 50 healthy controls) were examined in the study. Biochemical and hemostatic parameters were compared between various groups of subjects on day 1 and day 3 of admission to the hospital. RESULTS: Levels of prothrombin time (PT), fibrinogen, D-dimer, and C-reactive protein (CRP) were significantly higher in the severe AP group than in the mild AP group. Antithrombin III (AT III) levels were significantly lower in the severe AP group than in the mild AP group. D-dimer levels were 5 times higher than the reference limit in the severe group and 1.7 times higher than the reference limit in the mild group. This difference was statistically highly significant (< 0.0001). A positive correlation between D-dimer and CRP, D-dimer and fibrinogen, and between D-dimer and PT was recorded. CONCLUSIONS: Estimation of the levels of D-dimer on admission day provides an accurate method for the identification of patients who will develop systemic complications in the further course of AP. PMID- 26554238 TI - Rs219780 SNP of Claudin 14 Gene is not Related to Clinical Expression in Primary Hyperparathyroidism. AB - BACKGROUND: The CLDN14 gene encodes a protein involved in the regulation of paracellular permeability or ion transport at epithelial tight junctions as in the nephron. The C allele of the rs219780 SNP (single nucleotide polymorphism) of CLDN14 has been associated with renal lithiasis, high levels of parathormone (PTH), and with low bone mineral density (BMD) in healthy women. Our aim is to study the relationship between rs219780 SNP of CLDN14 and renal lithiasis, fractures, and BMD in patients with primary hyperparathyroidism (PHPT). METHODS: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analysed anthropometric data, history of fractures or kidney stones, biochemical parameters including markers for bone remodelling, abdominal ultrasound, and BMD and genotyping for the rs219780 SNP of CLDN14. RESULTS: We did not find any difference in the frequency of fractures or renal lithiasis between the genotype groups in PHPT patients. Moreover, we did not find any relationship between the T or C alleles and BMD or biochemical parameters. CONCLUSIONS: rs219780 SNP of CLDN14 does not appear to be a risk factor for the development of PHPT nor does it seem to influence the clinical expression of PHPT. PMID- 26554239 TI - Evaluation of the Post-Mortem Superoxide Dismutase, Glutathione Peroxidase Activities and Malondialdehyde Level in Renal and Brain Tissues: Is it Possible to Estimate Post-Mortem Interval Using these Parameters? AB - BACKGROUND: Estimation of the postmortem interval (PMI) is one major area of interest in forensic medicine. We investigated changes of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels in rat brain and renal tissues in the PMI and examined the potential changes which may be useful for an estimation of time of death. METHODS: Forty albino female rats were used in this study. The rats were sacrificed and divided into five groups: Group 1: 0 hour, Group 2: 6 hours, Group 3: 12 hours, Group 4: 24 hours, and Group 5: 48 hours. The rats were housed at room temperature (22 degrees C +/- 2 degrees C) for the defined period for each group, and their brains and kidneys were excised. RESULTS: The postmortem MDA levels were significantly different between groups for both renal and brain tissues (p = 0.003; p = 0.007). The diagnostic adequacy of MDA was calculated. Regarding SOD and GSH-Px, we were not able to obtain any date that would be useful for the prediction of PMI. CONCLUSIONS: According to this study, it is possible that an estimation of the PMI can be made using postmortem MDA levels. Regarding SOD and GSH-Px, we were not able to obtain any data that would be useful for the prediction of PMI. PMID- 26554240 TI - Investigation of the Hepato-Protective Effects of Imdur in a Rat Model of Chronic Mountain Sickness. AB - BACKGROUND: The objective of this study was to determine if the clinical nitrate, Imdur, has a hepato-protective effect in chronic mountain sickness (CMS). METHODS: A total of 60 SD rats were included in the study. Fifty rats were used to model CMS and were randomly divided into the following groups (10 rats per group): 1) plateau, 2) nifedipine, 3) low dose imdur, 4) moderate dose imdur, and 5) high dose imdur. The remaining 10 rats were used for the control group. Thirty days after the CMS model was established, according to the appropriate body weight of the rats, intragastric administration of the treatment groups commenced. After 15 days, changes in pulmonary artery pressure (PAP) and pathology of liver tissues were observed. Homocysteine (Hcy), interleukin-6 (IL 6), C-reactive protein (CRP), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) levels were also measured. RESULTS: Compared with the control group, the levels of PAP, Hcy, IL-6, CRP, and MDA of the rats in the plateau model group, nifedipine group, and imdur groups were elevated. The levels of SOD and GSH-PX in these groups decreased relative to the control group. The injured rat livers were observed under the light microscope, revealing that hypoxia had caused tissue damage. Compared with that of the plateau model group, the levels of PAP, Hcy, IL-6, CRP, and MDA of the rats in the high dose imdur group were decreased (p < 0.05), and the levels of SOD and GSH-PX were increased (p < 0.05). Except for IL-6, the other parameters were comparable to normal values and better than those of the nifedipine group. Liver tissue from the high dose imdur group demonstrated less tissue damage from pathological sections. CONCLUSIONS: High dose imdur has hepato-protective effects in CMS rat models. PMID- 26554241 TI - Expression of NK-Activating Receptor-NKp46/NCR1 on NK Cells in Patients with Severe Aplastic Anemia. AB - BACKGROUND: Severe aplastic anemia (SAA) is a kind of bone marrow failure caused by complex pathogenesis, mainly characterized by severe pancytopenia which causes anemia, hemorrhage, and infection. Natural killer (NK) cells, derived from hematopoietic stem cells (HSCs) or common lymphoid progenitors (CLP), play an important role in the innate immunity and adaptive immune responses. Of the receptors on NK cells, the NKp46/NCR1 is considered to be an important activating receptor for NK cells. However, the quantity and function of NKp46/NCR1 remains unknown. METHODS: The quantity of NKp46/NCR1 on NK cells in patients with SAA before and after immunosuppressive therapy (IST) was investigated by flow cytometry, quantitative real-time PCR, and western blot. After knockdown of the NKp46/NCR1 gene, NK cells were cultured with K562 cells to detect the function of NK cells. RESULTS: The results showed that the expression of NKp46/NCR1 in NK cells was significantly higher in untreated SAA patients than those in remission SAA and controls by FCM, qRT-PCR, and WB. After co-culturing with NK cells knockdown with siRNA-NKp46/NCR1, the apoptosis rate of K562 cells was significantly lower compared with the siRNA-scr group and control groups (7.08 +/ 5.23% vs. 11.31 +/- 7.20% and 10.30 +/- 6.08%, p < 0.05). CONCLUSIONS: We concluded that the decrease of total NK cells and the higher expressions of NKp46/NCR1 on them may be the reason for the hyperfunction of the immune system in SAA patients. PMID- 26554242 TI - Reversal of Chemoresistance in Human Lung Cancer Cell Line A549/Taxol by Synthetic Second Mitochondria-Derived Activator of Caspase Peptide. AB - BACKGROUND: Chemoresistance is a leading cause of treatment failure in advanced lung cancer, including that with the extensively prescribed taxol. Recently, a series of structurally unique second mitochondria-derived activators of caspase (Smac) that act as antagonists of inhibitor of apoptosis proteins (IAPs) have been discovered, exhibiting the ability of inducing enhanced apoptosis of various cancer cell types when combined with chemotherapy. In the present study, we synthesized the second mitochondria-derived activator of caspase peptide (Smac-N7 for short) and explored its capacity in combination with taxol in vitro. METHODS: The sensitivity assay and reversal ability of Smac-N7 were tested by MTT. Flow cytometry was used to analyze apoptosis of cells with Annexin V/PI double staining technique. Cell cloning ability was performed to reflect its biological behavior in each group. RESULTS: Concentrations with inhibitory rates < 10% were selected as the reversal value of Smac-N7 peptide using MTT. The reversal folds were 2.52, 3.26, 3.67, and 5.4 in taxol + Smac-N7 (0.0390625, 0.078125, 0.15625, 0.3125 MUg/mL, respectively), and concentrations of Smac-N7 and reversal folds appeared in an obvious positive correlation (r(s) = 1, p = 0.000). Apoptosis analyzed at 48 hours by flow cytometry showed the apoptotic rates in taxol and 0.0390625, 0.078125, 0.15625, and 0.3125 MUg/mL Smac-N7 + taxol groups were 15.4 +/- 1.09%, 20.8% +/- 2.18%, 28.4% +/- 4.17%, 37.64% +/- 6.41%, and 46.6% +/- 7.76%, respectively. Concentrations of Smac-N7 appeared to have negative correlations with PE and SF (r(s) = -1, p < 0.05), which showed that the cells' cloning ability in 0.3125 MUg/mL Smac-N7 + taxol group was worse than that of other groups. CONCLUSIONS: When combined with taxol, 0.3125 MUg/mL Smac-N7 peptide may significantly increase taxol-induced apoptosis in chemoresistant A549/taxol lung cells at 48 hours, and is potentially useful as a reversal agent in lung cancer therapy. PMID- 26554243 TI - Lipopolysaccharide Enhances Beta2-Glycoprotein I Activation of Nuclear Factor kappaB in Liver Cancer Cells. AB - BACKGROUND: Beta2-glycoprotein I (beta2GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong beta2GPI expression in hepatitis B related hepatocellular carcinoma (HCC) tissue and the combination of beta2GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-kappaB). To investigate whether lipopolysaccharide (LPS) enhances beta2GPI activation of NF-betaB and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-alpha; interleukin-1 beta, IL 1beta; alpha-fetoprotein, AFP) in the human hepatoma cell line, SMMC-7721. METHODS: Experimental samples were divided into 4 groups as follows: Group A- blank cell group (SMMC-7721); group B--low, medium, and high LPS concentration groups (1 ng/mL; 10 ng/mL; and 100 ng/mL, respectively); group C--beta2GPI transfected group; and group D--beta2GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-kappaB was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA. RESULTS: Degrees of NF-kappaB activation in groups B, C, and D were varied. NF-kappaB activation in group D was the most significant, and the expressions of downstream factors, TNF-alpha and IL-1beta, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency. CONCLUSIONS: LPS enhanced the signal transduction of beta2GPI in liver cancer cells leading to activation of NF-kappaB, which triggered downstream signal transduction and increased the expression of downstream factors. This suggests that LPS enhancement of beta2GPI signal transduction may play a role in promoting the development of liver cancer. PMID- 26554244 TI - Alteration of the Total Nuclear DNA Ploidy in Different Histopathological Liver Tissues Negative and Positive for HCV RNA. AB - BACKGROUND: Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-associated carcinogenesis are unknown. We aim to investigate the alteration of the total nuclear DNA content (ploidy) in different histopathological liver tissues infected with HCV and their relation to the seropositivity of HCV RNA. METHODS: Blood and liver tissues were collected from 26 patients. Diagnosis was carried out according to clinical and pathological examinations by specialized physicians. HCV RNA was detected in patients' sera and tissue samples by RT-PCR. To examine nuclear DNA ploidy, liver tissues were stained with blue Fulgen using the image analysis techniques. Finally, the patients' DNA content was examined by histochemical analysis depending on the optical density of DNA from liver biopsies using the grey image menu in each specimen. RESULTS: The HCV RT-PCR results demonstrated that 13/26 (50%) patients had detectable HCV RNA in their sera samples while 18/26 (69%) had detectable HCV RNA in liver tissues. The DNA content from those patients measured by image cytometry showed a high level of alteration of nuclear DNA ploidy and proliferation in liver tissues with HCC, less alteration of nuclear DNA ploidy in cirrhotic patients, and least proliferation nearly normal in liver fibrosis patients. Moreover, the results of histochemical analysis confirmed the DNA image cytometry results and showed that positive HCV RNA liver tissues had more DNA ploidy than negative HCV RNA liver tissues with statistical significance (p-value < 0.05). CONCLUSIONS: HCV positive liver tissue had alterations in DNA content (ploidy) which may lead to liver disease progression, malignant transformation of the liver cells and development of hepatocellular carcinoma. PMID- 26554245 TI - Photodynamic Therapy-Induced Apoptosis of Keloid Fibroblasts is Mediated by Radical Oxygen Species In Vitro. AB - BACKGROUND: It has been demonstrated that photodynamic therapy (PDT) is a promising treatment approach for hyperplastic dermatosis and results in a beneficial outcome. In the present study, PDT involving hematoporphyrin monomethyl ether (HMME) was applied to keloid fibroblasts (KFB), and the effects and the mechanism of action were explored. METHODS: Keloid fibroblastic cells were divided into four groups (PDT group, light alone group, HMME alone group, normal cultured group). Cell proliferation and apoptosis were observed. Radical oxygen species (ROS) were detected by means of dihydroethidium (DHE) and dihydrorhodamine (DHR123). ROS in the PDT group were also assessed after addition of tiron. RESULTS: Cell proliferation was inhibited in the PDT group (p < 0.05), while the rate of apoptosis was also clearly increased (p < 0.05). The levels of ROS were significantly higher in the PDT group than was observed in the other three groups (p < 0.05). With the addition of tiron the damaging effects were reduced. CONCLUSIONS: Our data indicated that HMME-mediated PDT could inhibit keloid fibroblast proliferation and could also induce apoptosis. This process was associated with the production of ROS. PMID- 26554246 TI - Detection of AKR1B10 in Peripheral Blood by Anti-AKR1B10-Conjugated CdTe/CdS Quantum Dots. AB - BACKGROUND: Aldo-ketoreductase family 1 member B10 (AKR1B10) is a novel prognostic predictor and therapeutic target for colorectal cancer (CRC), and enzyme-linked immunosorbent assays (ELISAs) and electrochemiluminescence (ELC) assays are sample-consuming and high-cost methods. Therefore, it is very necessary to develop a new, simple, and fast yet highly sensitive and specific method for the detection of AKR1B10 in serum. Semiconducting quantum dots (QDs) possess a high fluorescence quantum yield, stability against photobleaching, and size-controlled luminescence properties; thus, they are suitable for photoelectrochemical tumor marker detection, especially in complex biological samples. However, CdTe/CdS QDs have not been applied for the detection of AKR1B10 in serum. METHODS: AKR1B10 in peripheral blood has been established using anti AKR1B10-conjugated CdTe/CdS QDs and measurements. The assay sensitivity was determined by measuring the quenched fluorescence intensity of AKR1B10 at 0.5, 1, 2, 5, or 10 ng/mL in phosphate-buffered solution (PBS) or 0.25%, 0.5%, 1.0%, 2.0%, or 5% human serum diluted in PBS. The assay was optimized under different pH values (7.00 - 7.40) for different reaction durations (10 - 60 minutes). The specificity of anti-AKR1B10-QDs was determined by testing the inhibition of AKR1B10 activity with carcinoembryonic antigen (CEA), immunoglobulin G (IgG), or alpha-fetoprotein (AFP), each at 1 ng/mL. RESULTS: Under the optimized incubation time (30 minutes) at room temperature and optimal pH (7.1 - 7.2), a correlation between the decreased fluorescence intensity of anti-AKR1B10-conjugated CdTe/CdS QDs and the concentration of AKR1B10 in the range from 0.05 to 100 ng/mL was established. The assay was sensitive for the detection of AKR1B10 in the range from 0.05 to 100 ng/mL, and the detection limit was 0.02 ng/mL. The assay presented a high specificity because the anti-AKR1B10-conjugated CdTe/CdS QDs only reacted with AKR1B10 in the sera in the presence of CEA, IgG, or AFP. CONCLUSIONS: In conclusion, the immunofluorescence assay to detect AKR1B10 in serum using anti-AKR1B10-conjugated CdTe/CdS QDs was simple and fast yet presented high sensitivity and specificity. Our findings provide a promising tool for the early prediction of CRC. PMID- 26554247 TI - Increased Neutrophil to Lymphocyte Ratio is Associated with In-Hospital Mortality in Patients with Aortic Dissection. AB - BACKGROUND: i ne prognostic relevance of hematological parameters in cardiovascular diseases has been well demonstrated. The purpose of the present study is to investigate the association between the hematological parameters, particularly neutrophil to lymphocyte ratio (NLR), and outcomes of aortic dissection (AD). METHODS: Two hundred patients diagnosed with AD were retrospectively recruited and compared with 76 subjects with ascending aortic dilatation (AAD) and 92 subjects with normal aortic diameters. The independent relation between hematological parameters and in-hospital mortality was analyzed by regression analysis. RESULTS: The NLR was significantly higher in the AD group compared to the AAD and control groups (median 8.83 [8.13] vs. median 1.95 [1.10] vs. median 1.71 [0.77], respectively; p = 0.01). The NLR was higher in the deceased (n = 57) compared to the surviving patients (n = 143) (median 10.37 [10.86] vs. median 7.84 [8.17]; p = 0.01). Receiver operating curve (ROC) analysis revealed that a NLR measurement higher than > 8.78 predicted in-hospital mortality for patients with acute aortic dissection with a sensitivity of 67.4% and a specificity of 57.2% (AUC: 0.672; p = 0.01). In multivariate logistic regression analysis, increased aortic diameter, acute dissection, and increased levels of NLR remained as the independent markers of in-hospital mortality within the study population. CONCLUSIONS: In patients with AD, NLR levels were increased compared to patients with AAD and controls and were independently associated with in-hospital mortality. This finding implicates that admission hematological parameters may have clinical importance in evaluating the mortality risk in patients with AD. PMID- 26554248 TI - Activation of the Blood Coagulation System in Patients with Chronic Spontaneous Urticaria. AB - BACKGROUND: Ninty-five percent of chronic spontaneous urticaria (CSU) patients presented with signs of thrombin generation, and autologous plasma skin tests score positive. The aim of this study was to assess the initiators of blood coagulation that lead to thrombin generation and fibrinolysis in CSU patients. METHODS: The plasma level of activated factor VII, activator factor XII, fragment F1+2, and D-dimer were measured and analyzed in 103 patients with CSU and 76 control subjects. RESULTS: Mean D-dimer plasma levels were higher in patients than controls (0.41 +/- 0.44 MUg/mL vs. 0.21 +/- 0.26 MUg/ mL; p < 0.001). Mean F1+2 plasma levels were higher in patients than controls (11.17 +/- 17.65 nM vs. 5.97 +/- 9.42 nM; p = 0.048). Mean FVIIa plasma levels were higher in patients than controls (4.09 +/- 4.22 ng/mL vs. 2.97 +/- 1.59 ng/mL; p = 0.031). However, no significant difference was found on FXIIa plasma levels. On the other hand, all the coagulation factors (D-dimer, FVIIa, and F1+2) were significantly correlated with disease severity. CONCLUSIONS: The extrinsic pathway of the clotting cascade is activated in CSU and is correlated with the disease severity. The involvement of the coagulation pathway in CSU opens new perspectives for a better understanding of the pathogenesis and treatment of the disease. PMID- 26554249 TI - The Importance of Nucleated Red Blood Cells in Patients with Beta Thalassemia Major and Comparison of Two Automated Systems with Manual Microscopy and Flow Cytometry. AB - BACKGROUND: Nucleated red blood cells (NRBC) can be used as a marker of erythropoietic stress and help optimize transfusion therapy in patients with beta thalassemia major. The aim of this study was to determine this correlation; and compare two automated systems (Sysmex XE-2100, and Advia 2120i) with manual microscopy and flow cytometry (FCM). METHODS: Absolute NRBC counts and percentages (NRBC%) from 51 patients were analyzed with both automated and reference methods. The results were compared with levels of pre-transfusion hemoglobin and ferritin levels. RESULTS: The mean age of the included patients (31 female, 20 male) were 12.9 +/- 7.5 years. Mean levels of hemoglobin and ferritin were 9.5 +/- 1.2 g/dL and 1896 +/- 1194 ng/mL respectively. The NRBC% of two instruments did not significantly differ and correlated well (p < 0.0001, r2 = 0.984). NRBC% obtained with the XE-2100 and Advia 2120i versus manual microscopy also yielded high correlations (r2 = 0.951 and r2 0.981, respectively); however, absolute NRBC counts versus FCM yielded lower coefficients (r2 = 0.723 and r2 = 0.694, respectively). High serum ferritin levels were correlated with both NRBC% and counts with both instruments (p < 0.001) and hemoglobin levels lower than 9.0 g/dL had a negative correlation with NRBC% and NRBC counts with the Advia 2120i (p < 0.05, r = -0.495) but not with the XE-2100. CONCLUSIONS: Monitoring of NRBC% with both instruments can help optimize transfusion therapy for patients with beta thalassemia major. Following the NRBC% is more efficient than absolute counts. PMID- 26554250 TI - Automated On-Line Microdialysis Sampling Coupled with HPLC for Synchronous Determination of Puerarin in Subcutaneous Tissue and Plasma Following Topical Administration. AB - BACKGROUND: Studies on transdermal administration have shown that puerarin can permeate rat skin rapidly with long-term drug delivery, but there are no reports demonstrating whether topical use of puerarin can provide a steady plasma concentration to produce therapeutic effects. The aim of the study is to evaluate the percutaneous penetration and plasma concentration of puerarin after transdermal administration in experimental rats. METHODS: The skin and plasma concentration of puerarin was quantified by microdialysis, and the recovery was determined by retrodialysis. Puerarin microdialysate concentrations were measured by on-line high-performance liquid chromatography (HPLC). Puerarin release from gels was determined by analysis of the amount of remaining drug after dermal application to hairless skin. RESULTS: The average recoveries of puerarin in the skin and plasma over an 8-hour period were 31.49% and 15.5%. Puerarin was rapidly absorbed with transdermal administration, with the C(max) values of 30.64 MUg/mL and 3.53 MUg/mL, the AUC0 t-values of 11.60 and 1.48 MUg/mL per minute, for skin and plasma, respectively. CONCLUSIONS: The results indicate that the automated on line microdialysis technique can be used to detect the skin and plasma pharmacokinetics of puerarin and that the use of skin gel can provide an effective means of puerarin administration. PMID- 26554251 TI - Evaluation of the New Cyclosporine and Tacrolimus Automated Electrochemiluminescence Immunoassays under Field Conditions. AB - BACKGROUND: Careful monitoring of the post-transplantation immunosuppressant drugs (ISDs) cyclosporine (CsA) and tacrolimus (TAC) in whole blood is essential to prevent adverse drug events. Immunoassays represent the most widely used methodology for therapeutic drug monitoring. In this study, the technical performance of the new automated electrochemiluminescence immunoassays (ECLIAs) for CsA and TAC measurement were assessed under field conditions. METHODS: Residual whole blood samples from patients undergoing CsA or TAC therapy following organ transplant were used to evaluate the assays at six independent laboratories across four countries. Experiments included within-run imprecision using PreciControl ISD controls and recovery of commercial external quality assurance (EQA) scheme samples. Both assays were compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS), using methods routinely employed at each investigational site, as well as with an equivalent commercial chemiluminescent microparticle immunoassay (CMIA) and enzyme multiplied immunoassay (EMIT). RESULTS: Within-run imprecision testing gave coefficients of variation of <= 5% in the > 90.0 - 2000 ng/mL range for the CsA ECLIA and <= 4.2% in the 3.5 - 12 ng/mL range and <= 4.9% in the > 12 - 40 ng/mL range for the TAC ECLIA. EQA sample recovery by ECLIA gave a mean bias of 6.9% for CsA and 4.9% for TAC versus the spiked concentration or the mean LC-MS/MS value. Deming regression analysis of ECLIA method comparison to LC-MS/MS for all sites yielded a slope of 1.22, intercept 8.43 ng/mL and r = 0.97 for CsA and a slope of 1.22, intercept 0.51 ng/mL and r = 0.96 for TAC. Comparison with CMIA yielded a slope of 0.87, intercept 5.51 ng/mL and r = 0.97 for CsA and a slope of 0.98, intercept 0.12 ng/mL and r = 0.97 for TAC. Comparison with EMIT yielded a slope of 1.23, intercept -8.74 ng/mL and r = 0.96 for CsA. CONCLUSIONS: The CsA and TAC ECLIA compare favorably with existing commercial immunoassays and with LC-MS/MS. They represent modern generation assays that meet the demands of monitoring drug concentrations in current immunosuppressive regimens. This study also highlights the importance of standardizing protocols and LC-MS/MS methods to give improved comparability between ISD assays. PMID- 26554252 TI - CYP2C9 Genetic Polymorphism is a Potential Predictive Marker for the Efficacy of Rosuvastatin Therapy. AB - BACKGROUND: There is well-known inter-individual variability in the cholesterol lowering effect of statins. However, inter-individual variability in response to rosuvastatin treatment in subjects with hypercholesterolemia has not been clearly established. This study aimed to evaluate the associations of CYP2C9 genetic polymorphism with the efficacy and safety of rosuvastatin in Chinese patients with hyperlipidemia. METHODS: A total of 218 patients with hyperlipidemia were selected and treated with 10 mg rosuvastatin per day for 12 weeks. Blood samples were collected prior to the treatment and after 4, 8, and 12 weeks of treatment. Clinical biochemistry analyses for serum lipid profiles were performed. Genotyping for CYP2C9 polymorphisms was performed using allele-specific real-time PCR. RESULTS: 197 out of 218 patients featured a wild-type CYP2C9*1/*1 genotype, and 21 patients featured a CYP2C9*1/*3 or CYP2C9*3/*3 mutation genotype. No patients with CYP2C9*2 alleles were identified. Sixteen patients discontinued the medication due to adverse effects. No serious adverse events (i.e., hepatotoxicity or myolysis) were observed. After the 12 weeks of treatment, we observed significant reductions in total cholesterol (TC), triglycerides and low density lipoprotein (LDL) levels compared to baseline (p < 0.05). Patients with the mutant genotype showed a higher TC-lowering and LDL-lowing effect compared to those with wild-type genotypes (TC: 45.05% vs. 38.96%, p = 0.041; LDL: 44.97% vs. 39.28%, p = 0.029). The frequency of adverse drug reactions in the studied patients did not differ by CYP2C9 genotypes (p > 0.05). CONCLUSIONS: This study suggests that the CYP2C9 polymorphism may be involved in the lipid-lowering efficacy of rosuvastatin in patients with hyperlipidemia. PMID- 26554253 TI - Non-Invasive DNA Sampling for Molecular Analysis of Beta-Thalassemia: Amiable Alternative Sampling Methods with Accurate Results for Pediatric Patients. AB - BACKGROUND: Beta-thalassemia is the most common genetic disorder in Malaysia. Confirmation of the beta-globin gene mutations involved in thalassemia is usually carried out by molecular analysis of DNA extracted from leukocytes in whole blood. Molecular analysis is generally carried out when affected children are around 1 - 2 years as clinical symptoms are expressed during this period. Blood taking at this age can be distressing for the child. High yield and pure DNA extracted from non-invasive sampling methods can serve as alternative samples in molecular studies for genetic diseases especially in pediatric cases. METHODS: In this study, mouthwash, saliva, and buccal cytobrush samples were collected from beta-thalassemia major patients who had previously been characterized using DNA extracted from peripheral blood. DNA was extracted from mouthwash, saliva, and buccal cytobrush samples using the conventional inexpensive phenol-chloroform method and was measured by spectrophotometry for yield and purity. Molecular characterization of beta-globin gene mutations was carried out using the amplification refractory mutation system (ARMS). RESULTS: DNA extracted from mouthwash, saliva, and buccal cytobrush samples produced high concentration and pure DNA. The purified DNA was successfully amplified using ARMS. Results of the beta-globin gene mutations using DNA from the three non-invasive samples were in 100% concordance with results from DNA extracted from peripheral blood. CONCLUSIONS: The conventional in-house developed methods for non-invasive sample collection and DNA extraction from these samples are effective and negate the use of more expensive commercial kits. In conclusion, DNA extracted from mouthwash, saliva, and buccal cytobrush samples provided sufficiently high amounts of pure DNA suitable for molecular analysis of beta-thalassemia. PMID- 26554254 TI - Downregulation of MicroRNA-1 is Associated with Poor Prognosis in Hepatocellular Carcinoma. AB - BACKGROUND: The relationship between microRNA-1 (miR-1) expression and prognosis has not been reported in hepatocellular carcinoma (HCC). The present study aimed to explore the clinicopathological significance and the prognostic role of miR-1 in HCC. METHODS: The expression levels of miR-1 were quantified using real-time quantitative PCR (q-PCR) in 40 surgically resected HCC samples and matched adjacent non-cancerous tissues. RESULTS: MiR-1 expression was significantly downregulated in HCC compared with matched non-cancerous tissues. Aberrant miR-1 expression was significantly correlated with gender, expression of hepatitis B virus surface antigen (HBsAg), tumor differentiation, vein invasion, and TNM stage. Patients with low expression of miR-1 had significantly reduced overall survival compared with patients with high expression of miR-1 (p = 0.04).The multivariate Cox regression analysis indicated that miR-1 expression (HR = 2.79; p = 0.005), gender (HR = 0.087; p = 0.005), vein invasion (HR = 0.172; p = 0.007), and TNM stage (HR = 3.421; p = 0.001) were independent prognostic factors for overall survival. CONCLUSIONS: Low miR-1 expression is associated with shortened survival time. MiR-1 may act as a potential prognostic biomarker for HCC patients. PMID- 26554255 TI - Influence of Preanalytical Variables on Prothrombin Time, Activated Partial Thromboplastin Time, and Fibrinogen. AB - BACKGROUND: In the present study, the influence of preanalytical variables on prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen testing is investigated. METHODS: Samples collected from 104 patients were used for the study. PT, aPTT, and fibrinogen levels were tested with 50% filled tubes to investigate the influence of sample volume. We measured the same parameters immediately after sampling, after 6 hours, and after 24 hours to investigate the influence of storage time. Samples were also tested after 6 hours at 4 degrees C to investigate the influence of storage temperature. RESULTS: Use of 50%-filled tubes did not alter the results of PT and fibrinogen testing, but caused a significant bias to the aPTT test. The results of aPTT at 24 hours were also significantly different from results immediately after sampling. However, uncentrifuged citrated samples stored for 24 hours at room temperature may still be suitable for PT and fibrinogen testing. Incubation at 4 degrees C for up to 6 hours did not bias the results of PT, aPTT, or fibrinogen testing. CONCLUSIONS: Whilst aPTT is malleable to preanalytical variables, PT and fibrinogen showed stable results across variations in sample volume, storage time, and temperature. PMID- 26554256 TI - Splenectomy-Related Red Cell Lysis Resistance and Analytical Consequences. PMID- 26554257 TI - Value of academic research rigor for the field of healthcare management. PMID- 26554258 TI - Interview With Kevin E. Lofton, FACHE, CEO of Catholic Health Initiatives. PMID- 26554259 TI - Thinking Beyond the Affordable Care Act. PMID- 26554260 TI - Clinical Integration: A Cornerstone for Population Health Management. PMID- 26554261 TI - How Do Healthcare Employees Rate the Ethics of Their Organization? An Analysis Based on VA IntegratedEthics@ Staff Survey Data. AB - Healthcare organizations with an ethical culture experience higher levels of employee productivity, less staff turnover, better levels of patient safety, resource and cost savings, and higher levels of patient satisfaction. Employees' perceptions of the ethics of their organization are considered a good indicator of the ethics culture. How employees rate the ethics of their organization is not well understood. Previous research has identified a number of attributes that are salient to employees' perceptions in this area. However, little is known about how employees synthesize their perceptions of these attributes to rate the ethics of their organization. Without this knowledge, managers have little specific information to act on to improve practices that would in turn improve employees' perceptions of their organization's ethics. For this study, we used data from Department of Veterans Affairs' (VA) 2014 IntegratedEthics@ Staff Survey administered to Veterans Health Administration (VHA) staff. We used multivariate regression analyses to investigate how VHA employees weigh their perceptions of eight attributes of an ethical organization to inform an overall rating of the ethics of their organization. We found that employee perceptions of fairness, clarity of expectations, accountability, and leadership's prioritization of ethics had the strongest associations with the overall rating. In addition, employees disproportionately weighed their positive perceptions in determining their overall rating. Therefore, a strategy to improve employees' perceptions of these attributes could potentially have the greatest marginal return on investment with respect to improving employees' perceptions of the ethics of an organization. PMID- 26554262 TI - Practitioner application. PMID- 26554263 TI - Hospital Acquisitions Before Healthcare Reform. AB - The hospital industry has experienced increased consolidation in the past 20 years. Since 2010, in particular, there has been a large rise in the number of hospital acquisitions, and observers have suggested this is due in part to the expected impact of federal healthcare reform legislation. This article reports on a study undertaken to identify the market, management, and financial factors affecting acute care, community hospitals acquired between 2010 and 2012. We identified 77 such hospitals and compared them to other acute care facilities. To assess how different factors were associated with acquisitions, the study used multiple logistic regressions whereby market factors were included first, followed by management and financial factors. Study findings show that acquired hospitals were located in markets with lower rates of preferred provider organization (PPO) penetration compared with nonacquired hospitals. Occupancy rate was found to be inversely related to acquisition rate; however, case-mix index was significantly and positively related to a hospital's being acquired. Financial factors negatively associated with a hospital's being acquired included age of plant and cash flow margin. In contrast to the findings from earlier studies of hospital acquisitions, our results showed that acquired hospitals possessed newer assets. However, similar to the findings of other studies, the cash flow margin of acquired hospitals was lower than that of nonacquired facilities. PMID- 26554264 TI - Practitioner application. PMID- 26554265 TI - The Impact of Self-Rated Health Status on Patient Satisfaction Integration Process. AB - The purpose of this study was to investigate how patients' self-rated health status (SRHS) is associated with their attribute reaction integration process and, in turn, their overall ratings of hospitals. We collected patient satisfaction data from 70 hospitals by means of a patient satisfaction questionnaire. The sample included patients who were 18 years or older and discharged from the hospital from July 1, 2011, through June 30, 2012. Data for 36,528 patients were available for analysis. We conducted multiple linear regression analysis with patients' SRHS and interaction effects with nursing care, physician care, staff care, and room, while controlling for age, gender, race, and education. Study findings showed an association between SRHS levels and the patient's overall rating of the hospital; they also revealed interaction effects with nursing care, physician care, and staff care variables in the model. The statistically significant interaction effects indicate that for patients whose SRHS was less than excellent, physician care became more important and nursing care and staff care became less important compared with patients whose SRHS was excellent. When we consider the nature of medical care, this transition seems reasonable. We also found that it is reasonable to categorize patients into two groups: those whose SRHS is excellent and those whose SRHS is less than excellent (i.e., very good, good, fair, or poor). As the study findings show, these two groups of patients combined their attribute reactions differently. PMID- 26554266 TI - Practitioner application. PMID- 26554267 TI - The Relationship Between Hospital Value-Based Purchasing Program Scores and Hospital Bond Ratings. AB - Tax-exempt hospitals and health systems often borrow long-term debt to fund capital investments. Lenders use bond ratings as a standard metric to assess whether to lend funds to a hospital. Credit rating agencies have historically relied on financial performance measures and a hospital's ability to service debt obligations to determine bond ratings. With the growth in pay-for-performance based reimbursement models, rating agencies are expanding their hospital bond rating criteria to include hospital utilization and value-based purchasing (VBP) measures. In this study, we evaluated the relationship between the Hospital VBP domains--Clinical Process of Care, Patient Experience of Care, Outcome, and Medicare Spending per Beneficiary (MSPB)--and hospital bond ratings. Given the historical focus on financial performance, we hypothesized that hospital bond ratings are not associated with any of the Hospital VBP domains. This was a retrospective, cross-sectional study of all hospitals that were rated by Moody's for fiscal year 2012 and participated in the Centers for Medicare & Medicaid Services' VBP program as of January 2014 (N = 285). Of the 285 hospitals in the study, 15% had been assigned a bond rating of Aa, and 46% had been assigned an A rating. Using a binary logistic regression model, we found an association between MSPB only and bond ratings, after controlling for other VBP and financial performance scores; however, MSPB did not improve the overall predictive accuracy of the model. Inclusion of VBP scores in the methodology used to determine hospital bond ratings is likely to affect hospital bond ratings in the near term. PMID- 26554268 TI - Practitioner application. PMID- 26554269 TI - Rising incidence of morbidly adherent placenta and its association with previous caesarean section: a 15-year analysis in a tertiary hospital in Hong Kong. AB - OBJECTIVES: To identify the incidence of morbidly adherent placenta in the context of a rising caesarean delivery rate within a single institution in the past 15 years, and to determine the contribution of morbidly adherent placenta to the incidence of massive postpartum haemorrhage requiring hysterectomy. SETTING: A regional obstetric unit in Hong Kong. PATIENTS: Patients with a morbidly adherent placenta with or without previous caesarean section scar from 1999 to 2013. RESULTS: A total of 39 patients with morbidly adherent placenta were identified during 1999 to 2013. The overall rate of morbidly adherent placenta was 0.48/1000 births, which increased from 0.17/1000 births in 1999-2003 to 0.79/1000 births in 2009-2013. The rate of morbidly adherent placenta with previous caesarean section scar and unscarred uterus also increased significantly. Previous caesarean section (odds ratio=24) and co-existing placenta praevia (odds ratio=585) remained the major risk factors for morbidly adherent placenta. With an increasing rate of morbidly adherent placenta, more patients had haemorrhage with a consequent increased need for peripartum hysterectomy. No significant difference in the hysterectomy rate of morbidly adherent placenta in caesarean scarred uterus (19/25) compared with unscarred uterus (8/14) was noted. This may have been due to increased detection of placenta praevia by ultrasound and awareness of possible adherent placenta in the scarred uterus, as well as more invasive interventions applied to conserve the uterus. CONCLUSION: Presence of a caesarean section scar remained the main risk factor for morbidly adherent placenta. Application of caesarean section should be minimised, especially in those who wish to pursue another future pregnancy, to prevent the subsequent morbidity consequent to a morbidly adherent placenta, in particular, massive postpartum haemorrhage and hysterectomy. PMID- 26554270 TI - Use of insulin in diabetes: a century of treatment. AB - Insulin is a key player in the control of hyperglycaemia for patients with type 1 diabetes mellitus and selected patients with type 2 diabetes mellitus. There have been many advances in insulin drug delivery from its first administration as a crude pancreatic extract till today. The traditional and most predictable method for administration of insulin is by subcutaneous injection. Currently available insulin delivery systems include insulin syringes, infusion pumps, jet injectors, and pens. The major drawback of insulin therapy is its invasive nature. Non invasive delivery of insulin has long been a major goal for the treatment of diabetes mellitus. Although there have been improvements in insulin therapy since it was first conceived, it is still far from mimicking the physiological secretion of pancreatic beta-cells, and research to find new insulin formulations and new routes of administration continues. This article reviews the emerging technologies, including insulin inhalers, insulin buccal spray, insulin pill, islet cell transplant, and stem cell therapy, as treatment options for diabetes mellitus. PMID- 26554271 TI - Clinicopathological effects of pepper (oleoresin capsicum) spray. AB - OBJECTIVES: Pepper (oleoresin capsicum) spray is one of the most common riot control measures used today. Although not lethal, exposure of pepper spray can cause injury to different organ systems. This review aimed to summarise the major clinicopathological effects of pepper spray in humans. DATA SOURCES: MEDLINE, EMBASE database, and Cochrane Database of Systematic Reviews were used to search for terms associated with the clinicopathological effects of pepper spray in humans and those describing the pathophysiology of capsaicin. A phone interview with two individuals recently exposed to pepper spray was also conducted to establish clinical symptoms. STUDY SELECTION: Major key words used for the MEDLINE search were "pepper spray", "OC spray", "oleoresin capsicum"; and other key words as "riot control agents", "capsaicin", and "capsaicinoid". We then combined the key words "capsaicin" and "capsaicinoid" with the major key words to narrow down the number of articles. A search with other databases including EMBASE and Cochrane Database of Systematic Reviews was also conducted with the above phrases to identify any additional related articles. DATA EXTRACTION: All article searches were confined to human study. The bibliography of articles was screened for additional relevant studies including non-indexed reports, and information from these was also recorded. Non-English articles were included in the search. DATA SYNTHESIS: Fifteen articles were considered relevant. Oleoresin capsicum causes almost instantaneous irritative symptoms to the skin, eyes, and respiratory system. Dermatological effects include a burning sensation, erythema, and hyperalgesia. Ophthalmic effects involve blepharospasm, conjunctivitis, peri orbital oedema, and corneal pathology. Following inhalation, a stinging or burning sensation can be felt in the nose with sore throat, chest tightness, or dyspnoea. The major pathophysiology is neurogenic inflammation caused by capsaicinoid in the pepper spray. There is no antidote for oleoresin capsicum. Treatment consists of thorough decontamination, symptom-directed supportive measures, and early detection and treatment of systemic toxicity. Decontamination should be carefully carried out to avoid contamination of the surrounding skin and clothing. CONCLUSION: Pepper (oleoresin capsicum) spray is an effective riot control agent and does not cause life-threatening clinical effects in the majority of exposed individuals. Early decontamination minimises the irritant effects. PMID- 26554272 TI - Validation of the Dutch clinical prediction rule for ambulation outcomes in an inpatient setting following traumatic spinal cord injury. AB - STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the accuracy of a previously described Dutch clinical prediction rule for ambulation outcome in routine clinical practice. SETTING: Adult (?18 years) patients who were admitted to the Austin Hospital with a traumatic spinal cord injury between January 2006 and August 2014. METHODS: Data from medical records were extracted to determine the score of the Dutch clinical ambulation prediction rule proposed by van Middendorp et al. in 2011. A receiver-operating characteristics (ROC) curve was generated to investigate the performance of the prediction rule. Univariate analyses were performed to investigate which factors significantly influence ambulation after a traumatic spinal cord injury. RESULTS: The area under the ROC curve (AUC) obtained during the current study (0.939, 95% confidence interval (CI) (0.892, 0.986)) was not significantly different from the AUC from the original Dutch clinical prediction model (0.956, 95% CI (0.936, 0.976)). Factors that were found to have a significant influence on ambulation outcome were time spent in the ICU, number of days hospitalised and injury severity. Age at injury initially showed a significant influence on ambulation however, this effect was not apparent after inclusion of the 24 patients who died due to the trauma (and therefore did not walk after their injuries). CONCLUSION: The Dutch ambulation prediction rule performed similarly in routine clinical practice as in the original, controlled study environment in which it was developed. The potential effect of survival bias in the original model requires further investigation. PMID- 26554274 TI - Bladder management in individuals with chronic neurogenic lower urinary tract dysfunction. AB - STUDY DESIGN: Retrospective investigation. OBJECTIVES: To investigate the association of patient and injury characteristics with bladder evacuation by indwelling catheterization in patients with chronic neurogenic lower urinary tract dysfunction (NLUTD). SETTING: Tertiary urologic referral center. METHODS: The patient database was screened for patients with chronic (>12 months) NLUTD. Patient characteristics and bladder management details were collected. Binary logistic regression analysis was used to investigate the effects of the investigated factors on bladder evacuation by indwelling catheterization. RESULTS: The data of 1263 patients with a median age of 47 years (range 11-89 years) and a median NLTUD duration of 15.2 years (range 1.0-63.4 years) were investigated. The most common bladder evacuation method was intermittent catheterization (IC; 41.3%) followed by triggered reflex voiding (25.7%), suprapubic catheterization (11.8%), sacral anterior root stimulation (7.3%), spontaneous voiding (7.0%), abdominal straining (5.7%) and transurethral catheterization (1.3%). Female gender, tetraplegia, an age older than 45 years and injury duration were significant (<0.001) predictors of indwelling catheterization. The odds of bladder evacuation by indwelling catheterization were increased ~2.5, 3 and 4 times in women, patients older than 45 years and tetraplegics, respectively. CONCLUSIONS: IC is the most common bladder evacuation method. However, the majority of individuals with NLUTD are using other evacuation methods, because factors such as functional deficiencies, mental impairment or the social situation are relevant for choosing a bladder evacuation method. Individuals at risk of indwelling catheterization can be identified based on female gender, age, injury severity and injury duration. PMID- 26554273 TI - Top ten research priorities for spinal cord injury: the methodology and results of a British priority setting partnership. AB - STUDY DESIGN: This is a mixed-method consensus development project. OBJECTIVES: The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI). SETTING: The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers. METHODS: This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership. RESULTS: We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities. CONCLUSION: Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come. SPONSORSHIP: The NIHR Oxford Biomedical Research Centre provided core funding for this project. PMID- 26554275 TI - In Situ Integration of Anisotropic SnO2 Heterostructures inside Three-Dimensional Graphene Aerogel for Enhanced Lithium Storage. AB - Three-dimensional (3D) graphene aerogel (GA) has emerged as an outstanding support for metal oxides to enhance the overall energy-storage performance of the resulting hybrid materials. In the current stage of the studies, metals/metal oxides inside GA are in uncrafted geometries. Introducing structure-controlled metal oxides into GA may further push electrochemical properties of metal oxide GA hybrids. Using rutile SnO2 as an example, we demonstrated here a facile hydrothermal strategy combined with a preconditioning technique named vacuum assisted impregnation for in situ construction of controlled anisotropic SnO2 heterostructures inside GA. The obtained hybrid material was fully characterized in detail, and its formation mechanism was investigated by monitoring the phase transformation process. Rational integration of the two advanced structures, anisotropic SnO2 and 3D GA, synergistically led to enhanced lithium-storage properties (1176 mAh/g for the first cycle and 872 mAh/g for the 50th cycle at 100 mA/g) as compared with its two counterparts, namely, rough nanoparticles@3D GA and anisotropic SnO2@2D graphene sheets (618 and 751 mAh/g for the 50th cycle at 100 mA/g, respectively). It was also well-demonstrated that this hybrid material was capable of delivering high specific capacity at rapid charge/discharge cycles (1044 mAh/g at 100 mA/g, 847 mAh/g at 200 mA/g, 698 mAh/g at 500 mA/g, and 584 mAh/g at 1000 mA/g). The in situ integration strategy along with vacuum-assisted impregnation technique presented here shows great potential as a versatile tool for accessing a variety of sophisticated smart structures in the form of anisotropic metals/metal oxides within 3D GA toward useful applications. PMID- 26554276 TI - Characterization of Disinfection By-Products from Chromatographically Isolated NOM through High-Resolution Mass Spectrometry. AB - As levels of natural organic matter (NOM) in surface water rise, the minimization of potentially harmful disinfection by-products (DBPs) becomes increasingly critical. Here, we introduce the advantage that chromatographic prefractionation brings to investigating compositional changes to NOM caused by chlorination. Fractionation reduces complexity, making it easier to observe changes and attribute them to specific components. Under the conditions tested (0.1-0.4 g of Cl to g of C without further additives), the differences between highly and less oxidized NOM were striking. Highly oxidized NOM formed more diverse Cl-containing DPB, had a higher propensity to react with multiple Cl, and tended to transform so drastically as to no longer be amenable to electrospray-ionization mass spectral detection. Less-oxidized material tended to incorporate one Cl and retain its humiclike composition. N-containing, lipidlike, and condensed aromatic structure (CAS)-like NOM were selectively enriched in mass spectra, suggesting that such components do not react as extensively with NaOCl as their counterparts. Carbohydrate-like NOM, conversely, was selectively removed from spectra by chlorination. PMID- 26554279 TI - Effectiveness, Adverse Effects, and Safety of Medical Marijuana. PMID- 26554277 TI - Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure. AB - A randomized, multi-center study of adult cigarette smokers switched to tobacco heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects' experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products (ClinicalTrials.gov Identifier: NCT02061917). PMID- 26554280 TI - Graduates of Teaching Health Centers Are More Likely to Enter Practice in the Primary Care Safety Net. PMID- 26554281 TI - Nonsurgical Management of Knee Pain in Adults. AB - The role of the family physician in managing knee pain is expanding as recent literature supports nonsurgical management for many patients. Effective treatment depends on the etiology of knee pain. Oral analgesics-most commonly nonsteroidal anti-inflammatory drugs and acetaminophen-are used initially in combination with physical therapy to manage the most typical causes of chronic knee pain. The American Academy of Orthopaedic Surgeons recommends against glucosamine/chondroitin supplementation for osteoarthritis. In patients who are not candidates for surgery, opioid analgesics should be used only if conservative pharmacotherapy is ineffective. Exercise-based therapy is the foundation for treating knee osteoarthritis and patellofemoral pain syndrome. Weight loss should be encouraged for all patients with osteoarthritis and a body mass index greater than 25 kg per m2. Aside from stabilizing traumatic knee ligament and tendon tears, the effectiveness of knee braces for chronic knee pain is uncertain, and the use of braces should not replace physical therapy. Foot orthoses can be helpful for anterior knee pain. Corticosteroid injections are effective for short term pain relief in patients with osteoarthritis. The benefit of hyaluronic acid injections is controversial, and recommendations vary; recent systematic reviews do not support a clinically significant benefit. Small studies suggest that regenerative injections can improve pain and function in patients with chronic knee tendinopathies and osteoarthritis. PMID- 26554282 TI - Common Questions About Pressure Ulcers. AB - Patients with limited mobility due to physical or cognitive impairment are at risk of pressure ulcers. Primary care physicians should examine at-risk patients because pressure ulcers are often missed in inpatient, outpatient, and long-term care settings. High-risk patients should use advanced static support surfaces to prevent pressure ulcers and air-fluidized beds to treat pressure ulcers. Physicians should document the size and clinical features of ulcers. Cleansing should be done with saline or tap water, while avoiding caustic agents, such as hydrogen peroxide. Dressings should promote a moist, but not wet, wound healing environment. The presence of infection is determined through clinical judgment; if uncertain, a tissue biopsy should be performed. New or worsening pain may indicate infection of a pressure ulcer. When treating patients with pressure ulcers, it is important to keep in mind the patient's psychological, behavioral, and cognitive status. The patient's social, financial, and caregiver resources, as well as goals and long-term prognosis, should also be considered in the treatment plan. PMID- 26554283 TI - Obsessive-Compulsive Disorder: Diagnosis and Management. AB - Obsessive-compulsive disorder (OCD) is a chronic illness that can cause marked distress and disability. It is a complex disorder with a variety of manifestations and symptom dimensions, some of which are underrecognized. Early recognition and treatment with OCD-specific therapies may improve outcomes, but there is often a delay in diagnosis. Patients can experience significant improvement with treatment, and some may achieve remission. Recommended first line therapies are cognitive behavior therapy, specifically exposure and response prevention, and/or a selective serotonin reuptake inhibitor (SSRI). Patients with OCD require higher SSRI dosages than for other indications, and the treatment response time is typically longer. When effective, long-term treatment with an SSRI is a reasonable option to prevent relapse. Patients with severe symptoms or lack of response to first-line therapies should be referred to a psychiatrist. There are a variety of options for treatment-resistant OCD, including clomipramine or augmenting an SSRI with an atypical antipsychotic. Patients with OCD should be closely monitored for psychiatric comorbidities and suicidal ideation. PMID- 26554284 TI - A Systematic Approach to the Evaluation of a Limping Child. AB - A limp is defined as a deviation from a normal age-appropriate gait pattern resulting in an uneven, jerky, or laborious gait. It can be caused by pain, weakness, or deformity as a result of a variety of conditions. Transient synovitis is the most common diagnosis. Other causes of acute limp include contusion, foreign body in the foot, fracture, osteomyelitis, septic arthritis, reactive arthritis, and Lyme arthritis. Causes of chronic limp include rheumatic disease, dermatomyositis, acute rheumatic fever, inflammatory bowel disease, and systemic lupus erythematosus. Evaluation of a limping child should begin with a history focused on identifying pain, trauma, and associated systemic symptoms. For a limping child with focal findings on physical examination, initial imaging includes anteroposterior and lateral radiography of the involved site. If there are no focal findings on physical examination, radiography of both lower extremities should be performed. Laboratory testing is guided by history and physical examination findings. Septic arthritis of the hip should be suspected in a child with an oral temperature more than 101.3 degrees F (38.5 degrees C), refusal to bear weight, erythrocyte sedimentation rate more than 40 mm per hour, peripheral white blood cell count more than 12,000 per mm3 (12 * 109 per L), or C reactive protein level more than 20 mg per L (180.96 nmol per L). PMID- 26554285 TI - Scabies. PMID- 26554286 TI - Screening for Speech and Language Delay and Disorders in Children Five Years and Younger. PMID- 26554287 TI - Changing Facial Lesion. PMID- 26554290 TI - Knee Pain. PMID- 26554291 TI - Capture of 0.1-MUm aerosol particles containing viable H1N1 influenza virus by N95 filtering facepiece respirators. AB - Nosocomial infections pose an escalating threat to both patients and healthcare workers (HCWs). A widely recommended device for individual respiratory protection, the N95 filtering facepiece respirator (FFR) has been shown to provide efficient filtration of inert particles larger and smaller than the nominal most-penetrating particle size (MPPS) range, 0.03-0.3 MUm. Humans generate respiratory aerosols in the MPPS range, suggesting that short-range disease transmission could occur via small infectious particles. Data presented here show that the N95 FFR will afford a significant measure of protection against infectious particles as small as a bare H1N1 influenza virion, and that the capture mechanism does not discriminate in favor of, or against, biological particles. PMID- 26554292 TI - Comprehensive Two-Dimensional Hydrophilic Interaction Chromatography (HILIC) * Reversed-Phase Liquid Chromatography Coupled to High-Resolution Mass Spectrometry (RP-LC-UV-MS) Analysis of Anthocyanins and Derived Pigments in Red Wine. AB - Changes in anthocyanin chemistry represent some of the most important transformations involved in red wine aging. However, accurate analysis of the derived pigments, as required to study the evolution of anthocyanins and tannins during aging, is hampered by their extreme structural diversity, low levels, and the fact that many of these compounds have identical mass spectral characteristics. In this context, chromatographic separation is critical. In this contribution, the application of online hydrophilic interaction chromatography (HILIC) * reversed-phase liquid chromatography (RP-LC) separation coupled to high resolution mass spectrometry (MS) is described for the detailed characterization of anthocyanins and their derived pigments in aged red wine. A systematic approach was followed for the optimization of HILIC * RP-LC separation parameters using a capillary liquid chromatography (LC) system in the first dimension and an ultrahigh-pressure LC system in the second dimension to ensure maximum sensitivity and performance. Ninety four (94) anthocyanin-derived pigments were tentatively identified in one- and six-year-old Pinotage wines using accurate mass and fragmentation information obtained using quadrupole-time-of-flight mass spectrometry (Q-TOF-MS). Online HILIC * RP-LC-MS was found to offer high resolution separation, because of the combination of two different separation modes, while the structured elution order observed improved the certainty in compound identification. Therefore, this approach shows promise for the detailed elucidation of the chemical alteration of anthocyanins during wine aging. PMID- 26554293 TI - Study on 3'-UTR length polymorphism in peripheral blood mononuclear cells of uremia patient. AB - OBJECTIVE: The objective of this study was to measure the 3'-untranslated region (3'-UTR) polymorphism lengths in peripheral blood mononuclear cells (PBMCs) from uremia patients. METHOD: We sequenced the alternative polyadenylation sites in the 3'-UTR of PBMCs from 10 uremic patients and 10 healthy people to detect different gene expression levels between uremia patients and healthy controls. Quantitative reverse transcription polymerase chain reaction was used as validation. RESULT: Compared with the healthy control group, 691 genes in uremic patients had significantly different 3'-UTR lengths. Of these genes, 475 genes showed shortened 3'-UTRs, and the 3'-UTRs of 216 genes were lengthened. The verification results matched the original sequencing results. CONCLUSION: There were significant differences in 3'-UTR lengths between uremic patients and healthy controls, and analysis of the differential genes may contribute to the understanding of uremia pathogenesis. PMID- 26554294 TI - Human exposure assessment to a large set of polymer additives through the analysis of urine by solid phase extraction followed by ultra high performance liquid chromatography coupled to tandem mass spectrometry. AB - Polymer items are extensively present in the human environment. Humans may be consequently exposed to some compounds, such as additives, incorporated in these items. The objective of this work is to assess the human exposure to the main additives such as those authorized in the packaging for pharmaceutical products. The urinary matrix was selected to optimally answer this challenge because it has already been proven that the exposure to chemicals can be revealed by the analysis of this biological matrix. A multi-residue analytical method for the trace analysis at ng/mL in human urine was developed, and consisted of an extraction of analytes from urine by solid phase extraction (SPE) and an analysis by ultra-high performance liquid chromatography coupled to a tandem mass spectrometer (UHPLC-MS/MS). Even if the quantification of these compounds was an analytical challenge because of (i) the presence of these substances in the analytical process, (ii) the diversity of their physicochemical properties, and (iii) the complexity of the matrix, the optimized method exhibited quantification limits lower than 25ng/mL and recoveries between 51% and 120% for all compounds. The method was validated and applied to 52 human urines. To the best of our knowledge, this work presents the first study allowing the assessment of the occurrence of more than twenty polymer additives at ng/mL in human urine. PMID- 26554295 TI - Comparing two metabolic profiling approaches (liquid chromatography and gas chromatography coupled to mass spectrometry) for extra-virgin olive oil phenolic compounds analysis: A botanical classification perspective. AB - Over the last decades, the phenolic compounds from virgin olive oil (VOO) have become the subject of intensive research because of their biological activities and their influence on some of the most relevant attributes of this interesting matrix. Developing metabolic profiling approaches to determine them in monovarietal virgin olive oils could help to gain a deeper insight into olive oil phenolic compounds composition as well as to promote their use for botanical origin tracing purposes. To this end, two approaches were comparatively investigated (LC-ESI-TOF MS and GC-APCI-TOF MS) to evaluate their capacity to properly classify 25 olive oil samples belonging to five different varieties (Arbequina, Cornicabra, Hojiblanca, Frantoio and Picual), using the entire chromatographic phenolic profiles combined to chemometrics (principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA)). The application of PCA to LC-MS and GC-MS data showed the natural clustering of the samples, seeing that 2 varieties were dominating the models (Arbequina and Frantoio), suppressing any possible discrimination among the other cultivars. Afterwards, PLS-DA was used to build four different efficient predictive models for varietal classification of the samples under study. The varietal markers pointed out by each platform were compared. In general, with the exception of one GC-MS model, all exhibited proper quality parameters. The models constructed by using the LC-MS data demonstrated superior classification ability. PMID- 26554296 TI - Magnetic graphene - polystyrene sulfonic acid nano composite: A dispersive cation exchange sorbent for the enrichment of aminoalcohols and ethanolamines from environmental aqueous samples. AB - Present study aimed at graphene surface modification to achieve selective analyte binding in dispersive solid phase extraction. Magnetic graphene - polystyrene sulfonic acid (MG-PSS) cation exchange nano-composite was prepared by non covalent wrapping method. Composite was characterized by FT-IR and zeta potential. Material exhibited good dispersion in water and high exchange capacity of 1.97+/-0.16mMg(-1). Prepared nano-sorbent was then exploited for the cation exchange extraction and gas chromatography mass spectrometric analysis of Chemical Weapons Convention relevant aminoalcohols and ethanolamines from aqueous samples. Extraction parameters such as sorbent amount, extraction time, desorption conditions and sample pH were optimized and effect of common matrix interferences such as polyethylene glycol and metal salts was also studied. Three milligram of sorbent per mL of sample with 20min of extraction time at room temperature afforded 70-81% recoveries of the selected analytes spiked at concentration level of 1MUgmL(-1). Method showed good linearity in the studied range with r(2)>=0.993. The limits of detection and limits of quantification ranged from 23 to 54ngmL(-1) and 72 to 147ngmL(-1), respectively. The relative standard deviation for intra- and inter-day precision ranged from 4.6 to 10.2% and 7.4 to 14.8% respectively. Applicability of the method to different environmental samples as well as the proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW) was also ascertained. PMID- 26554298 TI - Hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for the quantification of uridine diphosphate-glucose, uridine diphosphate-glucuronic acid, deoxynivalenol and its glucoside: In-house validation and application to wheat. AB - Nucleotide sugars, the activated forms of monosaccharides, are important metabolites involved in a multitude of cellular processes including glycosylation of xenobiotics. Especially in plants, UDP-glucose is one of the most prominent members among these nucleotide-sugars, as it is involved in the formation of glucose conjugates of xenobiotics, including mycotoxins, but also holds a central role in the interconversion of energized sugars such as the formation of UDP glucuronic acid required for cell wall biosynthesis. Here, we present the first HILIC-LC-ESI-TQ-MS/MS method for the quantification of UDP-glucose and UDP glucuronic acid together with the Fusarium toxin deoxynivalenol (DON) and its major plant detoxification product DON-3-O-glucoside (DON-3-Glc) utilizing a polymer-based column. For sample preparation a time-effective and straightforward 'dilute and shoot' protocol was applied. The chromatographic run time was minimized to 9min including proper column re-equilibration. In-house validation of the method verified its linear range, intra- (1-7%) and interday (8-20%) precision, instrumental LODs between 0.6 and 10ngmL(-1), selectivity and moderate matrix effects with mean recoveries of 85-103%. To prove the methods applicability, we analyzed two sets of wheat extracts obtained from different cultivars grown under standardized greenhouse conditions. The results clearly demonstrated the suitability of the developed method to quantify UDP-glucose, DON and its masked form D3G in diluted wheat extracts. We observed differing concentration levels of UDP-glucose in the two wheat cultivars showing different resistance to the severe plant disease Fusarium head blight. We propose that the higher ability to detoxify DON into DON-3-Glc might be a consequence of the higher cellular UDP-glucose pool in the resistant cultivar. PMID- 26554297 TI - Selective capture of glycoproteins using lectin-modified nanoporous gold monolith. AB - The surface of nanoporous gold (np-Au) monoliths was modified via a flow method with the lectin Concanavalin A (Con A) to develop a substrate for separation and extraction of glycoproteins. Self-assembled monolayers (SAMs) of alpha-lipoic acid (LA) on the np-Au monoliths were prepared followed by activation of the terminal carboxyl groups to create amine reactive esters that were utilized in the immobilization of Con A. Thermogravimetric analysis (TGA) was used to determine the surface coverages of LA and Con A on np-Au monoliths which were found to be 1.31*10(18) and 1.85*10(15)moleculesm(-2), respectively. An in situ solution depletion method was developed that enabled surface coverage characterization without damaging the substrate and suggesting the possibility of regeneration. Using this method, the surface coverages of LA and Con A were found to be 0.989*10(18) and 1.32*10(15)moleculesm(-2), respectively. The selectivity of the Con A-modified np-Au monolith for the high mannose-containing glycoprotein ovalbumin (OVA) versus negative control non-glycosylated bovine serum albumin (BSA) was demonstrated by the difference in the ratio of the captured molecules to the immobilized Con A molecules, with OVA:Con A=2.3 and BSA:Con A=0.33. Extraction of OVA from a 1:3 mole ratio mixture with BSA was demonstrated by the greater amount of depletion of OVA concentration during the circulation with the developed substrate. A significant amount of captured OVA was eluted using alpha methyl mannopyranoside as a competitive ligand. This work is motivated by the need to develop new materials for chromatographic separation and extraction substrates for use in preparative and analytical procedures in glycomics. PMID- 26554299 TI - Clear Experimental Demonstration of Hole Gas Accumulation in Ge/Si Core-Shell Nanowires. AB - Selective doping and band-offset in germanium (Ge)/silicon (Si) core-shell nanowire (NW) structures can realize a type of high electron mobility transistor structure in one-dimensional NWs by separating the carrier transport region from the impurity-doped region. Precise analysis, using Raman spectroscopy of the Ge optical phonon peak, can distinguish three effects: the phonon confinement effect, the stress effect due to the heterostructures, and the Fano effect. The Fano effect is the most important to demonstrate hole gas accumulation in Ge/Si core-shell NWs. Using these techniques, we obtained conclusive evidence of the hole gas accumulation in Ge/Si core-shell NWs. The control of hole gas concentration can be realized by changing the B-doping concentration in the Si shell. PMID- 26554301 TI - Assessment of lighting needs by W-36 laying hens via preference test. AB - Light intensity, spectrum and pattern may affect laying hen behaviors and production performance. However, requirements of these lighting parameters from the hens' standpoint are not fully understood. This study was conducted to investigate hens' needs for light intensity and circadian rhythm using a light tunnel with five identical compartments each at a different fluorescent light intensity of <1, 5, 15, 30 or 100 lux. The hens were able to move freely among the respective compartments. A group of four W-36 laying hens (23 to 30 weeks of age) were tested each time, and six groups or replicates were conducted. Behaviors of the hens were continuously recorded, yielding data on daily time spent, daily feed intake, daily feeding time, and eggs laid under each light intensity and daily inter-compartment movement. The results show that the hens generally spent more time in lower light intensities. Specifically, the hens spent 6.4 h (45.4%) at 5 lux, 3.0 h (22.1%) at 15 lux, 3.1 h (22.2%) at 30 lux and 1.5 h (10.3%) at 100 lux under light condition; and an accumulation of 10.0 h in darkness (<1 lux) per day. The 10-h dark period was distributed intermittently throughout the day, averaging 25.0+/-0.4 min per hour. This hourly light-dark rhythm differs from the typical commercial practice of providing continuous dark period for certain part of the day (e.g. 8 h at night). Distributions of daily feed intake (87.3 g/hen) among the different light conditions mirrored the trend of time spent in the respective light intensity, that is, highest at 5 lux (28.4 g/hen, 32.5% daily total) and lowest at 100 lux (5.8 g/hen, 6.7%). Hen-day egg production rate was 96.0%. Most of the eggs were laid in <1 lux (61.9% of total) which was significantly higher than under other light intensities (P<0.05). Findings from this study offer insights into preference of fluorescent light intensity by the laying hens. Further studies to assess or verify welfare and performance responses of the hens to the preferred lighting conditions and rhythm over extended periods are recommended. PMID- 26554300 TI - Genetic basis of natural variation in body pigmentation in Drosophila melanogaster. AB - Body pigmentation in insects and other organisms is typically variable within and between species and is often associated with fitness. Regulatory variants with large effects at bab1, t and e affect variation in abdominal pigmentation in several populations of Drosophila melanogaster. Recently, we performed a genome wide association (GWA) analysis of variation in abdominal pigmentation using the inbred, sequenced lines of the Drosophila Genetic Reference Panel (DGRP). We confirmed the large effects of regulatory variants in bab1, t and e; identified 81 additional candidate genes; and validated 17 candidate genes (out of 28 tested) using RNAi knockdown of gene expression and mutant alleles. However, these analyses are imperfect proxies for the effects of segregating variants. Here, we describe the results of an extreme quantitative trait locus (xQTL) GWA analysis of female body pigmentation in an outbred population derived from light and dark DGRP lines. We replicated the effects on pigmentation of 28 genes implicated by the DGRP GWA study, including bab1, t and e and 7 genes previously validated by RNAi and/or mutant analyses. We also identified many additional loci. The genetic architecture of Drosophila pigmentation is complex, with a few major genes and many other loci with smaller effects. PMID- 26554302 TI - Association Between Polymorphisms of DNA Repair Genes and Risk of Schizophrenia. AB - AIMS: DNA repair gene polymorphisms have recently been implicated as potential pathogenic contributors of mental disorders. The aims of our study were to investigate the participation of nucleotide and base excision repair mechanisms in schizophrenia and to identify novel candidate DNA repair susceptibility genes. MATERIALS AND METHODS: For these purposes, we genotyped apurinic/apyrimidinic endonuclease 1 (APE1), human 8-oxoguanine DNA N-glycosylase 1 (hOGG1), X-ray repair cross-complementation group 1 (XRCC1), XRCC3, xeroderma pigmentosum group D (XPD), and xeroderma pigmentosum group G (XPG) genes in schizophrenia subjects, their healthy relatives, and unrelated healthy controls. RESULTS: Carriers of XRCC1 glutamine (Gln), XRCC3 threonine (Thr), hOGG1 cysteine (Cys), and XPD lysine (Lys) alleles were significantly more frequent among the cohort of schizophrenia patients than in controls. In contrast, the frequencies of XRCC3 methionine (Met) and XPD Gln allele carriers and hOGG1 serine (Ser)/Ser genotype carriers were higher among controls than in patients, suggesting a possible protective role for these gene variants against schizophrenia. Moreover, healthy relatives had significantly higher frequencies of XRCC3 Thr+ and XPD Lys+ genotypes than unrelated healthy controls. Minor allele frequencies, haplotypes, and overtransmitted alleles of DNA repair genes were also identified. CONCLUSION: Our findings support XRCC1, XRCC3, hOGG1, and XPD as risk genes for schizophrenia and suggest that altered DNA repair functions may be involved in schizophrenia pathophysiology. PMID- 26554304 TI - Attentional bias modification (ABM) training induces spontaneous brain activity changes in young women with subthreshold depression: a randomized controlled trial. AB - BACKGROUND: Attention bias modification (ABM) training has been suggested to effectively reduce depressive symptoms, and may be useful in the prevention of the illness in individuals with subthreshold symptoms, yet little is known about the spontaneous brain activity changes associated with ABM training. METHOD: Resting-state functional MRI was used to explore the effects of ABM training on subthreshold depression (SubD) and corresponding spontaneous brain activity changes. Participants were 41 young women with SubD and 26 matched non-depressed controls. Participants with SubD were randomized to receive either ABM or placebo training during 28 sessions across 4 weeks. Non-depressed controls were assessed before training only. Attentional bias, depressive severity, and spontaneous brain activity before and after training were assessed in both training groups. RESULTS: Findings revealed that compared to active control training, ABM training significantly decreased depression symptoms, and increased attention for positive stimuli. Resting-state data found that ABM training significantly reduced amplitude of low-frequency fluctuations (ALFF) of the right anterior insula (AI) and right middle frontal gyrus which showed greater ALFF than non-depressed controls before training; Functional connectivity strength between right AI and the right frontoinsular and right supramarginal gyrus were significantly decreased after training within the ABM group; moreover, the improvement of depression symptoms following ABM significantly correlated with the connectivity strength reductions between right AI and right frontoinsular and right supramarginal gyrus. CONCLUSION: These results suggest that ABM has the potential to reshape the abnormal patterns of spontaneous brain activity in relevant neural circuits associated with depression. PMID- 26554303 TI - IQGAP1 is a phosphoinositide effector and kinase scaffold. AB - Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is a lipid messenger that regulates a wide variety of cellular functions. The majority of cellular PI4,5P2 is generated by isoforms of the type I phosphatidylinositol phosphate kinases (PIPKI) that are generated from three genes, and each PIPKI isoform has a unique distribution and function in cells. It has been shown that the signaling specificity of PI4,5P2 can be determined by a physical association of PIPKs with PI4,5P2 effectors. IQGAP1 is newly identified as an interactor of multiple isoforms of PIPKs. Considering the versatile roles of IQGAP1 in cellular signaling pathways, IQGAP1 may confer isoform-specific roles of PIPKs in distinct cellular locations. In this mini review, the emerging roles of PIPKs that are regulated by an association with IQGAP1 will be summarized. Focuses will be on cell migration, vesicle trafficking, cell signaling, and nuclear events. PMID- 26554305 TI - Corrigendum. PMID- 26554306 TI - Liposome armed with herpes virus-derived gH625 peptide to overcome doxorubicin resistance in lung adenocarcinoma cell lines. AB - New delivery systems including liposomes have been developed to circumvent drug resistance. To enhance the antitumor efficacy of liposomes encapsulating anti cancer agents, we used liposomes externally conjugated to the 20 residue peptide gH625. Physicochemical characterization of the liposome system showed a size of 140 nm with uniform distribution and high doxorubicin encapsulation efficiency. We evaluated the effects of increasing concentrations of liposomes encapsulating Doxo (LipoDoxo), liposomes encapsulating Doxo conjugated to gH625 (LipoDoxo gH625), empty liposomes (Lipo) or free Doxo on growth inhibition of either wild type (A549) or doxorubicin-resistant (A549 Dx) human lung adenocarcinoma. After 72 h, we found that the growth inhibition induced by LipoDoxo-gH625 was higher than that caused by LipoDoxo with an IC50 of 1 and 0.3 MUM in A549 and A549 Dx cells, respectively. The data on cell growth inhibition were paralleled by an higher oxidative stress and an increased uptake of Doxo induced by LipoDoxo-gH625 compared to LipoDoxo, above all in A549 Dx cells. Cytometric analysis showed that the antiproliferative effects of each drug treatment were mainly due to the induction of apoptosis. In conclusion, liposomes armed with gH625 are able to overcome doxorubicin resistance in lung adenocarcinoma cell lines. PMID- 26554307 TI - CD47-retargeted oncolytic adenovirus armed with melanoma differentiation associated gene-7/interleukin-24 suppresses in vivo leukemia cell growth. AB - Our previous studies have suggested that harboring a soluble coxsackie-adenovirus receptor-ligand (sCAR-ligand) fusion protein expression cassette in the viral genome may provide a universal method to redirect oncolytic adenoviruses to various membrane receptors on cancer cells resisting to serotype 5 adenovirus infection. We report here a novel oncolytic adenovirus vector redirected to CD47+ leukemia cells though carrying a sCAR-4N1 expression cassette in the viral genome, forming Ad.4N1, in which 4N1 represents the C-terminal CD47-binding domain of thrombospondin-1. The infection and cytotoxicity of Ad.4N1 in leukemia cells were determined to be mediated by the 4N1-CD47 interaction. Ad.4N1 was further engineered to harbor a gene encoding melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), forming Ad.4N1-IL24, which replicated dramatically faster than Ad.4N1, and elicited significantly enhanced antileukemia effect in vitro and in a HL60/Luc xenograft mouse model. Our data suggest that Ad.4N1 could act as a novel oncolytic adenovirus vector for CD47+ leukemia targeting gene transfer, and Ad.4N1 harboring anticancer genes may provide novel antileukemia agents. PMID- 26554308 TI - Implication of epithelial-mesenchymal transition in IGF1R-induced resistance to EGFR-TKIs in advanced non-small cell lung cancer. AB - The underlying mechanisms for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in about 30%-40% of non-small cell lung cancer (NSCLC) patients remain elusive. Recent studies have suggested that activation of epithelial-mesenchymal transition (EMT) and type 1 insulin like growth factor receptor (IGF1R) is associated with acquired EGFR-TKIs resistance in NSCLC. Our study aims to further explore the mechanism of EMT and IGF1R in acquired EGFR-TKIs resistance in NSCLC cell lines with mutant (PC-9) or wild-type EGFR (H460). Compared to parental cells, EGFR-TKIs-resistant PC-9/GR and H460/ER cells displayed an EMT phenotype and showed overexpression of IGF1R. SiIGF1R in PC-9/GR and H460/ER cells reversed EMT-related morphologies and reversed their resistance to EGFR-TKIs. Exogenous IGF-1 alone induced EMT in EGFR TKIs-naive PC-9 and H460 cells and increased their resistance against EGFR-TKIs. Inducing EMT by TGF-beta1 in PC-9 and H460 cells decreased their sensitivity to EGFR-TKIs, whereas reversing EMT by E-cadherin overexpression in PC-9/GR and H460/ER cells restored their sensitivity to EGFR-TKIs. These data suggest that IGF1R plays an important role in acquired drug resistance against EGFR-TKIs by inducing EMT. Targeting IGF1R and EMT may be a potential therapeutic strategy for advanced NSCLC with acquired EGFR-TKIs resistance. PMID- 26554310 TI - Methylglyoxal-induced modification causes aggregation of myoglobin. AB - Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive alpha-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. We have investigated the in vitro effect of MG (200MUM) on the monomeric heme protein myoglobin (Mb) (100MUM) in a time-dependent manner (7 to 18days incubation at 25 degrees C). MG induces significant structural alterations of the heme protein, including heme loss, changes in tryptophan fluorescence, decrease of alpha-helicity with increased beta-sheet content etc. These changes occur gradually with increased period of incubation. Incubation of Mb with MG for 7days results in formation of the AGE adducts: carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87 and carboxyethyllysine or pyrraline carboxymethyllysine at Lys-133. On increasing the period of incubation up to 14days, additional AGEs namely, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139 have been detected. MG also induces aggregation of Mb, which is clearly evident with longer period of incubation (18days), and appears to have amyloid nature. MG-derived AGEs may thus have an important role as the precursors of protein aggregation, which, in turn, may be associated with physiological complications. PMID- 26554312 TI - Determination of sulfonamides in beeswax by liquid chromatography coupled to tandem mass spectrometry. AB - The manuscript presents the development of a new method for the quantification of 16 sulfonamides in beeswax. Different sample preparation techniques were tested and modified to maximise the recovery of the target analytes and minimise the amount of coeluted impurities under conditions that provide reproducible results. The proposed method consisted of melting and dilution of beeswax in a mixture of n-hexane and isopropanol followed by extraction with 2% acetic acid. The extract was cleaned up by solid-phase extraction using strong cation exchange phase. Determination of the sulfonamides was achieved by liquid chromatography coupled to tandem mass spectrometry with the use of a pentafluorophenyl analytical column and applying a gradient elution with acetonitrile and 0.01% acetic acid as mobile phases. The limits of detection and limits of quantification ranged from 1 to 2MUg/kg and from 2 to 5MUg/kg, respectively. The recoveries varied between 65.2% and 117.8% while coefficient of variation of the method was less than 24.2% under intermediate precision conditions. Finally, the method was applied to the analysis of real samples of beeswax from beekeepers and commercial foundations manufacturers. PMID- 26554309 TI - Expression of androgen receptor splice variants in clinical breast cancers. AB - The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERalpha-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERalpha-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer. PMID- 26554313 TI - Pharmacokinetics and tissue distribution study of PA-824 in rats by LC-MS/MS. AB - A simple, sensitive and rapid LC-MS/MS method has been developed and validated for determination of PA-824 in rat biological samples using darunavir as internal standard. Chromatographic separation was achieved on an Inertsil((r))ODS3 C18 column (150mm*4.6mm, 5MUm) using gradient elution of methanol-0.1% ammonia in water (90:10, v/v) with fast gradient elution at a flow rate of 0.6mL/min and run time of 5min. The mass spectrometer was run in positive electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The optimized ion transition pairs for quantitation were m/z360.1 >m/z175.0 for PA-824, m/z548.5->m/z504.2 for IS. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, matrix effect and robustness. All validation parameters met the acceptance criteria according to regulatory guidelines. The LLOQ was 0.05MUg/mL. The calibration curves showed a good linearity over the concentration range of 0.05-50MUg/mL. The calibration curves for all biological samples showed good linearity (r(2)>0.9978) over the concentration ranges tested. The recoveries obtained for PA-824 were >=88.8%. The developed method was successfully applied to investigate the pharmacokinetics and tissue distribution of PA-824 in rats following oral administration. It was also the first study to investigate the tissue distribution of PA-824 in rats following oral administration. PMID- 26554314 TI - Mobile Phone Apps to Promote Weight Loss and Increase Physical Activity: A Systematic Review and Meta-Analysis. AB - BACKGROUND: To our knowledge, no meta-analysis to date has assessed the efficacy of mobile phone apps to promote weight loss and increase physical activity. OBJECTIVE: To perform a systematic review and meta-analysis of studies to compare the efficacy of mobile phone apps compared with other approaches to promote weight loss and increase physical activity. METHODS: We conducted a systematic review and meta-analysis of relevant studies identified by a search of PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from their inception through to August 2015. Two members of the study team (EG-F, GF-M) independently screened studies for inclusion criteria and extracted data. We included all controlled studies that assessed a mobile phone app intervention with weight-related health measures (ie, body weight, body mass index, or waist circumference) or physical activity outcomes. Net change estimates comparing the intervention group with the control group were pooled across studies using random effects models. RESULTS: We included 12 articles in this systematic review and meta-analysis. Compared with the control group, use of a mobile phone app was associated with significant changes in body weight (kg) and body mass index (kg/m(2)) of -1.04 kg (95% CI -1.75 to -0.34; I2 = 41%) and -0.43 kg/m(2) (95% CI -0.74 to -0.13; I2 = 50%), respectively. Moreover, a nonsignificant difference in physical activity was observed between the two groups (standardized mean difference 0.40, 95% CI -0.07 to 0.87; I2 = 93%). These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSIONS: Evidence from this study shows that mobile phone app-based interventions may be useful tools for weight loss. PMID- 26554315 TI - Effective and Neurobiologically Sound. PMID- 26554317 TI - Reproducible Success. PMID- 26554316 TI - Trans-Sector Integrated Treatment in Psychosis and Addiction. AB - BACKGROUND: Patients with psychosis often develop comorbid addiction, with a lifetime prevalence of ca. 50%. Dual diagnoses are considered hard to treat. Long term integrated treatment programs might improve such patients' outcomes, at least to a moderate extent, but they have not yet been adequately studied or implemented in Germany to date. METHODS: 100 dual diagnosis patients participated in a single-center, randomized, controlled trial under standard hospital treatment conditions. They were randomly allotted to two groups. Patients in the intervention group were admitted to a specialized open hospital ward, where they were given integrated treatment, including disorder-specific group therapy. Their treatment was continued with further disorder-specific group therapy in the outpatient setting. Patients in the control group were admitted to an open general psychiatric ward and received treatment as usual, but no disorder specific treatment either during their hospitalization or in the subsequent outpatient phase. Follow-up examinations were performed three, six, and twelve months after inclusion. The primary outcome was defined as the changes in substance use and abstinence motivation. The secondary outcome consisted of the patients' satisfaction with treatment and with life in general, retention rate, psychopathology, rehospitalizations, and global level of functioning. RESULTS: The patients in the intervention group developed higher abstinence motivation than those in the control group (p = 0.009) and transiently reduced their substance use to a greater extent (p = 0.039 at three months). They were also more satisfied with their treatment (group effect: p = 0.011). Their global level of functioning and their retention rate were also higher, but these differences did not reach statistical significance. CONCLUSION: Low-threshold, motivational, integrated treatment programs with psycho-educative and behavioral therapeutic elements may be helpful in the treatment of dual diagnosis patients and should be more extensively implemented as part of standard hospital treatment. Larger scale, methodologically more complex studies will be needed to identify subgroups of patients that respond to such treatments in different ways. PMID- 26554318 TI - In Reply. PMID- 26554319 TI - The Diagnosis and Treatment of Ectopic Pregnancy. AB - BACKGROUND: Extrauterine pregnancy is a complication of the first trimester of pregnancy that arises in 1.3-2.4% of all pregnancies. METHODS: This review is based on articles and guidelines retrieved by a selective PubMed search. RESULTS: The presentation of extrauterine pregnancy is highly variable, ranging from an asymptomatic state, to pelvic pain that is worse on one side, to tubal rupture with hemorrhagic shock. 75% of tubal pre gnancies can be detected by transvaginal ultrasonography. In patients with a vital extrauterine pregnancy, the human chorionic gonadotropin concentration generally doubles within 48 hours. Laparoscopy is the gold standard of treatment. Two randomized, controlled trials comparing organ-preserving treatment with ablative surgery revealed no significant difference in pregnancy rates after the intervention, but precise details of the surgical procedures were not provided, and long-term fertility data are lacking. Metho - trexate therapy should be used only for strict indications. CONCLUSION: Further randomized, controlled trials with longer follow up will be needed to answer currently open questions about the potential for individualized surgical treatment and the proper role of pharmacotherapy. PMID- 26554320 TI - Primun non nocere, polypharmacy and pharmacogenetics. PMID- 26554321 TI - Troublesome Disguises. PMID- 26554322 TI - Beyond Urinary Tract Infections (UTIs) and Delirium: A Systematic Review of UTIs and Neuropsychiatric Disorders. AB - Urinary tract infections (UTIs) are among the most common bacterial infections. Although comorbid UTI in geriatric patients with delirium or dementia is well known, the prevalence and scope of the association with other neuropsychiatric disorders is unclear. We performed a systematic review of the association between UTIs and delirium, dementia, psychotic disorders, and mood disorders in hospitalized patients. We identified studies by searching PubMed, PsycInfo, and Web of Knowledge, and the reference lists of identified studies and review papers. Seventeen publications met the inclusion criteria. The primary findings were: (1) 88% of publications reported a positive association between UTIs and neuropsychiatric disorders; (2) 47% reported that the clinical course of a neuropsychiatric disorder may be precipitated or exacerbated by a UTI; (3) the mean weighted prevalence of UTIs in subjects was 19.4% for delirium, 11.2% for dementia, 21.7% for nonaffective psychotic disorders, and 17.8% for mood disorders. Our findings, which must be interpreted carefully given the heterogeneity among the studies, suggest that UTIs are highly comorbid in hospitalized patients and may precipitate or exacerbate some neuropsychiatric disorders. The association extends beyond geriatric patients with delirium, affects males and females, and includes adults with psychotic and mood disorders. These findings underscore the important interface between physical and mental health. Potential underlying mechanisms are also reviewed, including complex interactions between the immune system and the brain. PMID- 26554323 TI - Disclosure of Use and Abuse of Controlled Substances Among Psychiatric Outpatients. AB - BACKGROUND: Prescription drug abuse is a serious health concern and is considered a nationwide epidemic. Patients often fail or refuse to disclose the use of controlled substances, leaving prescribers and pharmacies unaware of the potential for harmful drug interactions and risk of overdose. Psychiatric patients are especially vulnerable to controlled substance misuse. OBJECTIVES: To determine hazardous patterns of prescription drug use among psychiatric outpatients and to raise awareness about the importance of reviewing information provided by prescription drug monitoring programs (PDMPs). METHODS: The medical records of 150 patients attending the Adult Outpatient Psychiatric Clinic at the Los Angeles County+University of Southern California (LAC+USC) Medical Center from July 2012 through May 2013 were reviewed. Patient activity reports were generated from California's PDMP. Nondisclosure of controlled substance use was identified by a discrepancy between patient reporting of prescriptions according to the medical records and PDMP reports. A "pattern suggestive of prescription drug abuse" was defined as having one or more of the following: within-class prescriptions from multiple providers and/or within-class early refills or within class overlapping prescriptions picked up within 10 days of each other. RESULTS: Of the 150 patients, 113 were found in California's PDMP database. Of these 113 patients, 81 had obtained 111 prescriptions for controlled substances in the past 12 months. Of these 111 prescriptions, 52 (47%) were not disclosed to the primary psychiatrist, of which 14 (27%) revealed patterns consistent with prescription drug abuse. CONCLUSIONS: Reviewing PDMP databases before prescribing controlled substances should be considered a standard prescribing practice to prevent abuse, diversion, and adverse medical outcomes. PMID- 26554324 TI - Quality of Sleep in Patients With Bipolar I Disorder During Remission. AB - BACKGROUND AND GOALS: Sleep disturbances have been noted not only during affective episodes in bipolar disorder, but also between affective episodes. The goal of this study was to assess and identify determinants of sleep quality in patients with bipolar I disorder. METHODS: This cross-sectional study enrolled patients with bipolar disorder who were currently in remission. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Mood symptoms were evaluated using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (Ham-D). Adherence was assessed using the Medication Adherence Rating Scale. RESULTS: The mean age in the sample (N=103) was 37.4 years; 44.7% of the sample were men. On the basis of PSQI scores, 41 patients (39.8%) were poor sleepers. Poor sleepers had significantly higher Ham-D scores (mean score of 1.8 vs. 0.9, P=0.012) and higher rates of medication nonadherence (36.6% vs. 11.3%, P=0.002). The relationship between Ham-D scores and sleep quality did not remain significant when the sleep-related items on the Ham-D were removed. Logistic regression analysis suggested that medication nonadherence was the only independent predictor of poor sleep quality in this study. CONCLUSIONS: A significant proportion of patients with bipolar disorder who are in remission have sleep problems that seem to be independent of core symptoms of depression. PMID- 26554325 TI - Efficacy of Ketamine in Bipolar Depression: Systematic Review and Meta-analysis. AB - OBJECTIVE: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression. METHODS: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis. A random effect model was used to calculate the pooled SMDs. Heterogeneity was assessed using the Cochran Q test and I statistic. RESULTS: Of the 721 articles that were screened, 5 studies that enrolled a total of 125 subjects with bipolar depression (mean age, 44.6+/-4.3 y and 65.6% females) were included in the systematic review; 3 randomized controlled trials (69 subjects) were included in the meta-analysis. The meta-analysis showed significant improvement in depression among patients receiving a single dose of intravenous ketamine compared with those who received placebo (SMD=-1.01; 95% confidence interval, -1.37, -0.66; P<0.0001). The maximum improvement was observed 40 minutes after the ketamine infusion. No heterogeneity was observed between the studies (Cochran Q test P=0.38, I=0%). The 2 studies that were excluded from the meta-analysis also showed significant improvement in depression after ketamine therapy. Individual studies also reported improvement in anhedonia and suicidal ideation after ketamine therapy. None of the subjects had serious side effects, and the side effects were similar between the ketamine and placebo groups. CONCLUSIONS: This study suggests that ketamine is effective in treatment resistant bipolar depression and may reduce suicidal ideation and anhedonia. PMID- 26554326 TI - A Way of Conceptualizing Benzodiazepines to Guide Clinical Use. AB - Benzodiazepines are medications that are widely used for a number of different therapeutic indications and in a wide range of patients in terms of age and health status. Presented here is a simple 2 by 2 way of classifying all of the most commonly used benzodiazepines. This conceptualization is based on the most clinically relevant ways of differentiating these drugs: (a) their affinity for their common and predominant mechanism of action, the benzodiazepine-binding site of the gamma-aminobutyric acid (GABA)-A iontropic receptor (ie, the chloride ion channel); and (b) their pharmacokinetics (ie, their half-lives and metabolism). The science underlying this conceptualization is presented and then its clinical applicability is discussed. This system can help clinicians select the most appropriate benzodiazepine for their patients and better understand how to switch between these medications to minimize withdrawal symptoms; it also provides a rational basis for cautiously using these agents in combination when necessary, in a manner analogous to the combined use of short-acting and long-acting forms of insulin. PMID- 26554327 TI - The Spectrum of Psychoanalytic Therapies: For the Person Behind the Diagnosis. AB - Therapies based on psychoanalytic theory and practice are individualized to the unique needs of each patient. They are best viewed on a continuum, a spectrum of approaches that are modulated according to the difficulties and the character structure of each person as they manifest themselves at that moment in the person's history. As people change over the course of treatment, the treatment modality may evolve accordingly. The many elements of a psychoanalytically based therapy move along that continuum in a way better calibrated on an analogic curve than on a digital scale with discrete gradations. This requires that the analyst or therapist be attuned to the subtle shifts in the dynamic equilibrium of the patient's mental life. Psychoanalysis and psychodynamic psychotherapy are distinct macro ways to categorize and code for psychoanalytically derived treatments that operate at different but overlapping micro ranges of the analogic continuum. PMID- 26554328 TI - A Case of Capgras Syndrome Related to Hypothyroidism. AB - Hypothyroidism is commonly associated with a variety of psychiatric conditions, most commonly depression and cognitive impairment, but up to 5% to 15% of symptomatically hypothyroid patients may develop a nonaffective psychosis, classically referred to as "myxedema madness." We report the case of a woman who developed Capgras syndrome in the context of hypothyroidism, and whose psychosis rapidly resolved with levothyroxine supplementation. To date, very few cases of Capgras syndrome related to hypothyroidism have been reported. The pathophysiology of this condition remains unclear but it may be related to global cerebral hypometabolism or possibly to increased cerebral dopamine. Given the robust response of "myxedema madness" to thyroid replacement, psychiatrists should remain vigilant for covert hypothyroidism in patients with psychosis and atypical histories or presentations. PMID- 26554329 TI - Cushing Disease Presenting as Primary Psychiatric Illness: A Case Report and Literature Review. AB - We report the case of a woman with long-standing refractory depression and psychotic features who was eventually diagnosed with Cushing disease. After surgical treatment of a pituitary adenoma, she experienced gradual psychiatric recovery and was eventually able to discontinue all psychotropic medication. We review the psychiatric components of Cushing disease, implications of psychiatric illnesses for the treatment and prognosis of Cushing disease, and potential pathophysiological mechanisms linking glucocorticoid excess to psychiatric illness. PMID- 26554330 TI - Adaptive and Maladaptive Means of Using Facebook: A Qualitative Pilot Study to Inform Suggestions for Development of a Future Intervention for Depression. AB - Existing literature examining the relation between social networking sites and mental health is primarily based on correlational methods and presents mixed findings. Many researchers neglect to examine the cognitive and behavioral processes used while online. This study's qualitative approach strives to understand how individuals with elevated depressive symptoms may use Facebook following an interpersonal stressor. Participants' narration of their Facebook use was coded. Common adaptive uses included using Facebook to seek social support, actively communicate, distract, recall positive memories, and reappraise negative thoughts. Maladaptive uses included engaging in social comparison, ruminating, and recalling negative memories. Feedback regarding development of a future intervention was also elicited. Suggestions included using Facebook to view positive, interesting, or meaningful information, distract, garner social support, and engage in social activities. Findings indicate that how one engages with Facebook after an interpersonal stressor may affect adjustment and may help to inform the development of a novel, Facebook-based intervention. PMID- 26554331 TI - The Symptoms of Trauma Scale (SOTS): An Initial Psychometric Study. AB - The Symptoms of Trauma Scale (SOTS) is a 12-item, interview-based, clinician rated measure that assesses the severity of a range of trauma-related symptoms. This pilot study evaluated its use and psychometric properties in an outpatient setting that provides treatment to survivors of chronic interpersonal trauma. Thirty participants completed self-report measures of posttraumatic stress symptoms, depression, dissociation, self-esteem, and affect dysregulation; the participants also participated separately in a semistructured interview based on the SOTS conducted by 2 trained interviewers. SOTS composite severity scores for DSM-IV posttraumatic stress disorder (PTSD) and complex PTSD (cPTSD), DSM-5 PTSD, and PTSD dissociative subtype, and total traumatic stress symptoms generally had acceptable internal consistency and interrater reliability. Evidence of convergent, discriminant, criterion, and construct validity was found for the SOTS composite PTSD scores, although potential limitations to validity that require further research and refinement of the measure were identified for the SOTS total and DSM-IV cPTSD scores and the hyperarousal, affect dysregulation, and dissociation items. Interviewers and interviewees described the interview as efficient, informative, and well tolerated. Implications for clinical practice and research to refine the SOTS are discussed. PMID- 26554332 TI - Oxidized antithrombin is a dual inhibitor of coagulation and angiogenesis: Importance of low heparin affinity. AB - Endogenous proteins that promote vascular endothelial cell based inhibition of angiogenesis are an attractive option for antitumor therapy. Inactive cleaved and latent conformations of antithrombin (AT) are antiangiogenic, but not its native form which is an inhibitor of proteases involved in blood coagulation. Unlike native, the cleaved and latent conformations are reactive center loop inserted conformations which binds heparin with very low affinity. We use a sulfoxy modified AT to assess the role of reactive center loop insertion and heparin affinity in antiangiogenic function. Chorioallantoic membrane assay (CAM) shows that antiangiogenic activity of latent and oxidized AT are better than thalidomide, a potent antiangiogenic drug. Wound healing experiments suggest that latent and oxidized conformations can influence endothelial cell migration. Latent and cleaved conformations of AT shows an increase in alpha-helical content in the presence of unfractionated heparin, but not the oxidized AT. Unlike the loop inserted polymer, cleaved and latent conformations, oxidized AT has factor Xa inhibitory activity indicating that loop insertion is not necessary for antiangiogenic role. The results of our study establish that active conformation of AT can become antiangiogenic while maintaining its anticoagulant activity possibly through chelation of low affinity heparin in the vicinity of endothelial cell. PMID- 26554333 TI - Detection, Identification, and Prevalence of Pathogenic Vibrio parahaemolyticus in Fish and Coastal Environment in Jordan. AB - Vibrio parahaemolyticus is widely distributed in the marine environments and considered the leading cause of human gastroenteritis in Asian countries. A total of 150 marketed fish and 50 water and sediment samples from the Gulf of Aqaba were examined for the prevalence of pathogenic strains of V. parahaemolyticus. A total of 132 typical isolates obtained from the primary selective medium (thiosulfate-citrate bile salt sucrose agar) and showed positive biochemical properties were subjected to confirmation by polymerase chain reaction targeting the gyrB and toxR genes. These genes were confirmed at rates of 82% (108 isolates) and 72% (95 isolates), respectively. The toxR positive isolates were tested for the presence of thermolabile hemolysin (tlh), thermostable direct hemolysin (tdh), and tdh-related hemolysin (trh) virulence genes. Accordingly, the prevalence rates of pathogenic V. parahaemolyticus were 4%, 8%, and 12% in sediment, water, and fish samples, respectively. The 16S rRNA amplification and sequences were conducted for confirmation of the isolates and showing the relatedness among these isolates. The results showed that both 16S rRNA and toxR assays had same sensitivity and tested isolates had high nucleotide similarity irrespective of their sources. PMID- 26554334 TI - [Reforming the Surgical Section of the Practical Year at Ludwig-Maximilians University Munich]. PMID- 26554335 TI - [Quality Management in Medicine: What the Surgeon Needs to Know]. AB - Quality management (QM) is a method used in the field of economics that was adopted late by the medical sector. The coincidence of quality management and what is referred to as economisation in medicine frequently leads to QM being - incorrectly - perceived as part of the economisation problem rather than as part of its solution. Quality assurance defines and observes key performance indicators for the achievement of quality objectives. QM is a form of active management that intends to systematically exclude the effects of chance. It is supposed to enable those in charge of an institution to deal with complex processes, to influence them and achieve quality even under unfavourable circumstances. Clearly defined written standards are an important aspect of QM and allow for 80 % of patients to be treated faster and less labour-intensively and thus to create more capacity for the individual treatment of the 20 % of patients requiring other than routine care. Standards provide a framework to rely on for department heads and other staff alike. They reduce complexity, support processes in stress situations and prevent inconsistent decisions in the course of treatment. Document management ensures transparent and up-to-date in-house standards and creates continuity. Good documents are short, easy to use, and, at the same time, comply with requirements. Specifications describe in-house standards; validation documents provide a forensically sound documentation. Quality management has a broad impact on an institution. It helps staff reflect on their daily work, and it initiates a reporting and auditing system as well as the systematic management of responses to surveys and complaints. Risk management is another aspect of QM; it provides structures to identify, analyse, assess and modify risks and subject them to risk controlling. Quality management is not necessarily associated with certification. However, if certification is intended, it serves to define requirements, increase motivation for the implementation of measures to be taken, and provide long-term continuity in newly adopted processes. Specialist certificates issued by medical associations frequently emphasise an interdisciplinary treatment approach; however, their certification processes are often of poor quality. The effectiveness and efficiency is evident for individual QM instruments in medicine. It is very likely that quality management improves effectiveness in the whole field of medicine, but this has yet to be proved. PMID- 26554336 TI - Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium. AB - In this study our main objective was to find out a novel target of the major bioactive green tea polyphenol, Epigallocatechin-3-gallate (EGCG), in cervical carcinoma HeLa cells. We found that EGCG showed antiproliferative activity against HeLa cells through depolymerization of cellular microtubule. EGCG also prevented the reformation of the cellular microtubule network distorted by cold treatment and inhibited polymerization of tubulin in cell-free system with IC50 of 39.6 +/- 0.63 MUM. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the alpha-subunit of tubulin at the interphase of the alpha-and beta heterodimers and very close to colchicine binding site. The binding is entropy driven (DeltaS(0) was 18.75 +/- 1.48 cal K(-1) mol(-1)) with Kd value of 3.50 +/- 0.40 MUM. This is a novel mechanism of antipriliferative activity of EGCG. PMID- 26554337 TI - Benzene oxide is a substrate for glutathione S-transferases. AB - Benzene is a known human carcinogen which must be activated to benzene oxide (BO) to exert its carcinogenic potential. BO can be detoxified in vivo by reaction with glutathione and excretion in the urine as S-phenylmercapturic acid. This process may be catalyzed by glutathione S-transferases (GSTs), but kinetic data for this reaction have not been published. Therefore, we incubated GSTA1, GSTT1, GSTM1, and GSTP1 with glutathione and BO and quantified the formation of S phenylglutathione. Kinetic parameters were determined for GSTT1 and GSTP1. At 37 degrees C, the putative Km and Vmax values for GSTT1 were 420 MUM and 450 fmol/s, respectively, while those for GSTP1 were 3600 MUM and 3100 fmol/s. GSTA1 and GSTM1 did not exhibit sufficient activity for determination of kinetic parameters. We conclude that GSTT1 is a critical enzyme in the detoxification of BO and that GSTP1 may also play an important role, while GSTA1 and GSTM1 seem to be less important. PMID- 26554338 TI - Photopatterning Proteins and Cells in Aqueous Environment Using TiO2 Photocatalysis. AB - Organic contaminants adsorbed on the surface of titanium dioxide (TiO2) can be decomposed by photocatalysis under ultraviolet (UV) light. Here we describe a novel protocol employing the TiO2 photocatalysis to locally alter cell affinity of the substrate surface. For this experiment, a thin TiO2 film was sputter coated on a glass coverslip, and the TiO2 surface was subsequently modified with an organosilane monolayer derived from octadecyltrichlorosilane (OTS), which inhibits cell adhesion. The sample was immersed in a cell culture medium, and focused UV light was irradiated to an octagonal region. When a neuronal cell line PC12 cells were plated on the sample, cells adhered only on the UV-irradiated area. We further show that this surface modification can also be performed in situ, i.e., even when cells are growing on the substrate. Proper modification of the surface required an extracellular matrix protein collagen to be present in the medium at the time of UV irradiation. The technique presented here can potentially be employed in patterning multiple cell types for constructing coculture systems or to arbitrarily manipulate cells under culture. PMID- 26554339 TI - An automated method to assay locomotor activity in third instar Drosophila melanogaster larvae. AB - INTRODUCTION: The purpose of these studies was to describe a novel application of an automated data acquisition/data reduction system, DanioVisionTM by Noldus. DanioVisionTM has the ability to detect changes in locomotor activity in third instar Drosophila melanogaster larvae. The noncompetitive GABAA receptor antagonist picrotoxin (PTX), was used as a pharmacologic agent to decrease locomotor activity. METHODS: Two strains of Drosophila were used in these studies; wild-type flies and flies with a mutation in the Rdl gene (Rdl(MD-RR)). Rdl(MD-RR)Drosophila are naturally occurring mutants that express an aberrant form of the GABAA receptor, which has a lower affinity for PTX, but not GABA itself. Larvae, extracted from food in 20% sucrose, were randomly placed into vials containing vehicle or PTX (0.03-3mM). After incubation of 2-24h, individual larvae were put in each well of a 6-well culture plate previously coated with 2% agar, the plate was then placed in the DanioVisionTM apparatus. The activity of individual larva was recorded for 5 min, digitized and analyzed using Ethovision(r) XT software. RESULTS: Incubation of third instar wild-type larvae in 1mM PTX for 4 or 24h decreased activity; whereas, a 2h incubation in PTX was without effect. PTX caused a concentration-dependent decrease in activity as demonstrated by consistently reduced locomotor activity with 1.0 and 3.0mM: 0.3mM resulted in variable decreases in locomotor activity and 0.03 mM yielded no effect. By contrast, PTX did not affect activity in Rdl(MD-RR) larvae even at the highest concentration, 3.0mM. DISCUSSION: Using an automated data acquisition system, it was found that PTX decreases activity in third instar Drosophila larvae due to a selective blockade of the GABAA receptor. The method will reduce the likelihood of human error and bias, as well as increase the speed and ease of data collection and analysis. PMID- 26554340 TI - High-Level Primary Clarithromycin Resistance of Helicobacter pylori in Algiers, Algeria: A Prospective Multicenter Molecular Study. AB - Knowledge of local antibiotic resistance is crucial to adaptation for the choice of the optimal first-line treatment for Helicobacter pylori infection. Clarithromycin is a key component of the standard triple therapy largely used worldwide and, more particularly, in Algeria. Clarithromycin resistance is the main risk factor for treatment failure. The aim of this study was to evaluate, for the first time in Algeria, the prevalence of the primary resistance of H. pylori to clarithromycin. We conducted a prospective study (2008-2014) that included 195 Algerian patients referred for gastroduodenal endoscopy to two University Hospitals, one General Hospital, and several private gastroenterologists in Algiers (Algeria). One gastric biopsy was collected for the molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin with a quadruplex real-time PCR using Scorpion primers. The Scorpion PCR detected H. pylori DNA in 91 biopsies (47%). A mutation conferring resistance to clarithromycin was detected in 32 of the 91 positive patients (35%) and in 29 of the 88 positive patients never previously treated for an H. pylori infection (33%). The prevalence of primary resistance of H. pylori to clarithromycin was 33% in the Algerian population being studied. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Algerian population that we report leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Algeria. PMID- 26554342 TI - Transannular E...E' Interactions in Neutral, Radical Cationic, and Dicationic Forms of cyclo-[E(CH2CH2CH2)2E'] (E, E' = S, Se, Te, and O) with Structural Feature: Dynamic and Static Behavior of E...E' Elucidated by QTAIM Dual Functional Analysis. AB - The nature of the transannular E-*-E' interactions in neutral, radical cationic, and dicationic forms of cyclo-E(CH2CH2CH2)2E' (1) (E, E' = S, Se, Te, and O) (1, 1(*+), and 1(2+), respectively) is elucidated by applying QTAIM dual functional analysis (QTAIM-DFA). Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 for the data of E-*-E' at BCPs in QTAIM-DFA, where * emphasizes the existence of BCP. Plots for the fully optimized structures are analyzed by the polar coordinate (R, theta) representation. Those containing the perturbed structures are by (thetap, kappap): thetap corresponds to the tangent line of the plot, and kappap is the curvature. While (R, theta) describes the static nature, (thetap, kappap) represents the dynamic nature of interactions. The nature is well-specified by (R, theta) and (thetap, kappap). E-*-E' becomes stronger in the order of 1 < 1(*+) < 1(2+), except for O-*-O. While E-*-E' (E, E' = S, Se, and Te) in 1(2+) are characterized as weak covalent bonds, except for S-*-Te (MC nature through CT) and Se-*-Te (TBP nature through CT), O-*-E' seems more complex. The behavior of E-*-E' in 1(2+) is very close to that of cyclo-E(CH2CH2CH2)E' (E, E' = S, Se, Te, and O), except for O-*-O. PMID- 26554341 TI - Social Goals and Grade as Moderators of Social Normative Influences on Adolescent Alcohol Use. AB - BACKGROUND: The literature distinguishes 2 types of social normative influences on adolescent alcohol use, descriptive norms (perceived peer alcohol use) and injunctive norms (perceived approval of drinking). Although theoretical formulations suggest variability in the salience and influence of descriptive and injunctive norms, little is understood regarding for whom and when social norms influence adolescent drinking. Strong agentic and communal social goals were hypothesized to moderate the influence of descriptive and injunctive norms on early adolescent alcohol use, respectively. Developmental changes were also expected, such that these moderating effects were expected to get stronger at later grades. METHODS: This longitudinal study included 387 adolescents and 4 annual assessments (spanning 6th to 10th grade). Participants completed questionnaire measures of social goals, social norms, and alcohol use at each wave. RESULTS: Multilevel logistic regressions were used to test prospective associations. As hypothesized, descriptive norms predicted increases in the probability of alcohol use for adolescents with strong agentic goals, but only in later grades. Injunctive norms were associated with increases in the probability of drinking for adolescents with low communal goals at earlier grades, whereas injunctive norms were associated with an increased probability of drinking for adolescents with either low or high communal goals at later grades. Although not hypothesized, descriptive norms predicted increases in the probability of drinking for adolescents high in communal goals in earlier grades, whereas descriptive norms predicted drinking for adolescents characterized by low communal goals in later grades. CONCLUSIONS: The current study highlights the importance of social goals when considering social normative influences on alcohol use in early and middle adolescence. These findings have implications for whom and when normative feedback interventions might be most effective during this developmental period. PMID- 26554343 TI - Interaction between fasudil hydrochloride and bovine serum albumin: spectroscopic study. AB - The interaction between fasudil hydrochloride (FSD) and bovine serum albumin (BSA) was investigated using fluorescence and ultraviolet spectroscopy under imitated physiological conditions. The Stern-Volmer quenching model has been successfully applied and the results revealed that FSD could quench the intrinsic fluorescence of BSA effectively via static quenching. The binding constants and binding sites for the BSA-FSD system were evaluated. The corresponding thermodynamic parameters obtained at different temperatures indicated that hydrophobic force played a major role in the interaction of FSD and BSA. The distance between the donor (BSA) and the acceptor (FSD) was obtained according to fluorescence resonance energy transfer (FRET). Synchronous fluorescence spectroscopy and FT-IR spectra showed that the conformation of BSA was changed in the presence of FSD. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26554344 TI - Synthesis, characterization and enhanced gas sensing performance of porous ZnCo2O4 nano/microspheres. AB - In recent years, spinel-type compounds have attracted great interest because of their gem-like qualities. However, little is known of their gas sensing properties. We report, in this paper, on a self-assembly method to prepare porous ZnCo2O4 (ZCO) nano/microspheres by a facile one-step solvothermal process and subsequent annealing. Abundant techniques were used to characterize the morphology and structure of the as-obtained compounds. Our data indicate that the hierarchical nano/microspheres are constructed from numerous nanoparticles primarily, which have a higher specific surface area (ca. 77.3 m(2) g(-1)) and are of uniform diameter (ca. 1 MUm). To demonstrate their potential application, gas sensors based on the as-synthesized ZCO nano/microspheres were fabricated to test their sensing performance, whose sensing behaviours correspond to p-type semiconductors. The test results also indicate that porous spinel-type compounds have an excellent kinetic response to ethanol at an operating temperature of 175 degrees C and a superior selectivity. As such, hierarchical porous ZnCo2O4 nano/microspheres will hold promising potential in the gas sensor field. PMID- 26554345 TI - Can new technologies improve upper limb performance in grown-up diplegic children? AB - BACKGROUND: Few systematic studies describe rehabilitation trainings for upper limb in diplegic children with cerebral palsy (CP), who - especially once grown up - are often not considered as a target for rehabilitation interventions. AIM: In this pilot study, we describe the details and the effectiveness of an intensive, technology assisted intervention for upper limb. SETTING: The treatment combines the utilization of Armeo(r) Spring with a training focused on hand/finger fluency and dexterity in a pre-post treatment experimental design. POPULATION: Participants were ten school-aged children (mean age 11.2) with bilateral CP and diplegia, attending mainstream schools. METHODS: Participants underwent 40 therapy sessions in four weeks. Armeo(r) Spring measures, standardized motor and perceptual outcome indexes, as well as everyday life indicators were utilized to assess the effect of the intervention. RESULTS: Upper limb coordination, fluency and quality of movements mainly of hands and fingers significantly improved, with a good transferability to everyday life also in areas not specifically trained, such as self-care abilities and mobility. Probably due to the visual feedback provided by the virtual reality setting (which was all in one the context, the incentive and the product of activities), perceptual abilities significantly improved, too. CONCLUSIONS: Our study suggests the importance of intervention on upper limb even in milder CP diplegic forms and in relatively grown-up children. The possibility of modification at least partially relies on learning processes that are active all along development and benefit from stimulation. CLINICAL REHABILITATION IMPACT: Though further studies with control groups and follow-up perspective are needed to confirm, new technologies offer interesting possibilities to be integrated into new evidence based rehabilitation models. PMID- 26554346 TI - Enhancing the Performance of Amorphous-Silicon Photoanodes for Photoelectrocatalytic Water Oxidation. AB - Herein, hydrogenated amorphous Si (a-Si:H) covered with a thin layer of CoOx is applied as photoanode for PEC water splitting. The thin layer of CoOx effectively protects a-Si:H from the corrosive electrolyte and quantitative oxidation of water to oxygen was observed. A high applied bias photon-to-current efficiency of 2.34 % was achieved using an intrinsic absorber and an additional p-type layer. This work shows that a-Si:H with a sandwich-like structure, in which each layer has its own functionality, can be applied as an efficient and stable photoanode for PEC water oxidation. PMID- 26554347 TI - Pharmacokinetics in Early Drug Research. PMID- 26554348 TI - Progress Toward the Validation of Alternative Tests. AB - ECVAM's role in the practical validation of replacement alternative methods for use in regulatory testing is reviewed, including an outline of the criteria which have been used in determining ECVAM's priorities. Some of the difficulties which have arisen in validation studies are discussed, and solutions to these are proposed, with particular emphasis on ensuring that methods are sufficiently well developed to enter the validation process, and on the ECVAM prevalidation scheme for encouraging protocol optimisation and the prior assessment of interlaboratory transferability. Comments are made on problems encountered in selecting test materials backed by adequate in vivo data and in undertaking appropriate in vivo/in vitro comparisons. PMID- 26554349 TI - Preselection of Potential Cancerostatics by Automatic Analysis of Suspended and Adherent Cells Incubated in Microplates. AB - Alternative toxicological screening programmes, without the use of animal experiments, are intended to eliminate dangerous substances and to find new pharmacologically active agents in cell cultures. They can also provide information on the cytostatic activities of the agents. Intercalating cytostatics which bind DNA were selected by measuring the statistical distributions of the cell diameters of K-562 and L-929 cells by using an electronic cell analyser (CASY1). These compounds were identified by cell enlargement or from flat concentration-activity curves created with the cell analyser system. Incubation for 72 hours with DNA-binding agents, such as doxorubicin, daunorubicin and Mitoxantron(r), resulted in enlargement of cell diameter and cell volume. The antineoplastic agents actinomycin D and ambazone had no comparable effect. Comparisons of the different parameters obtained with CASY1 measurement were performed with Microsoft EXCEL. PMID- 26554350 TI - Toxicity of 20 Chemicals from the MEIC Programme Determined by Growth Inhibition of L-929 Fibroblast-like Cells. AB - The Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme is an international project aimed at evaluating the relevance of in vitro tests in predicting human toxicity. We have screened 20 chemicals (MEIC codes 31-50) from the programme, by using a cytotoxicity test based on growth inhibition of the mouse fibroblast-like L-929 cell line. Inhibition of cell growth was determined by the neutral red uptake method, which is well established and is used for screening the cytotoxicity of chemicals and plastics for pharmaceuticals and medical devices. The concentrations causing 50% inhibition of cell growth after a 72-hour exposure period varied from 3.1MUM for hexachlorophene, to 1.4mM for caffeine. This is within the same range as results recently obtained with five other cell models. However, with some chemicals (chloroform, carbon tetrachloride and dichloromethane), no reliable results were obtained. These substances could not be dissolved in a reproducible way in any of the solvents used and, furthermore, they were highly volatile, which led to difficulties in maintaining the concentrations. PMID- 26554351 TI - A New Perspective on the Formation of Stratum Corneum Intercellular Space. PMID- 26554352 TI - Targeting divalent metal cations with Re(I) tetrazolato complexes. AB - In order to exploit their potential as versatile luminescent sensors, four new Re(I)-tetrazolato complexes with the general formula fac-[Re(CO)3(diim)(L)], where diim is 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen) and L(-) is either the anion 5-(2'-pyridyl)tetrazolato (2-PTZ(-)) or 5-(2' quinolyl)tetrazolato (2-QTZ(-)), were prepared and fully characterized. In all cases, the regioselective coordination of the Re(I) center through the N2 atom of the tetrazolato ring was observed. This particular feature ensures the availability of the diiminic (N^N) site that was systematically incorporated into the structure of the 2-PTZ(-) and 2-QTZ(-) ligands for further coordination with metal cations. Such a diimine-type coordination mode was preliminarily tested by using the mononuclear Re(I) complexes as N^N ligands for the preparation of two [(N^N)Cu(POP)] cationic species, where POP is the chelating diphosphine bis[2 (diphenylphosphino)phenyl]ether. The X-ray structures of the resulting Re(I) Cu(I) dyads revealed that the Re(I) mononuclear complexes effectively behaved as chelating N^N ligands with respect to the [Cu(POP)](+) fragment, the coordination of which also resulted in significant modification of the Re(I)-centered luminescence. With these data in hand, the luminescent sensing abilities of the four new Re(I) tetrazolato complexes were screened with respect to divalent metal ions of toxicological and biological importance such as Zn(II), Cd(II) and Cu(II). The interaction of the Re(I) complexes with Zn(II) and Cd(II) was witnessed by the evident blue shift (Deltalambdamax = 22-36 nm) of the emission maxima, which was also accompanied by a significant elongation of the emission lifetimes. On the contrary, the addition of the cupric ion caused substantial quenching of the radiative processes originating from the Re(I) luminophores. PMID- 26554353 TI - Combined Alport syndrome and Klinefelter syndrome. AB - To date, there have been a very limited number of case reports on combined Alport syndrome (AS) and Klinefelter syndrome (KS). We herein describe the case of a 9 month-old boy diagnosed with concomitant AS and KS. KS was detected on chromosomal analysis of the amniotic fluid, and hematuria/proteinuria was identified in urinary screening at 6 months of age. Renal biopsy indicated AS, with complete deficit of the alpha5 chain of type IV collagen in the glomerular basement membranes. On genetic analysis for AS, de novo homozygote mutation (c.3605-2a > c) was seen in the gene encoding alpha5 chain of type IV collagen (COL4A5) on the X chromosomes of maternal origin. This is the first case report of combined AS and KS diagnosed during infancy, and it indicates the need to consider the concurrent existence of these two disorders in infants with urine abnormalities, even in the absence of a family history. PMID- 26554354 TI - Standardization or Centralization: Can One Have One Without the Other? Circumferential Resection Margins and Rectal Cancer. PMID- 26554355 TI - Erratum to: Novel citation-based search method for scientific literature: application to meta-analyses. PMID- 26554356 TI - Lacinutrix gracilariae sp. nov., isolated from the surface of a marine red alga Gracilaria sp. AB - A Gram-stain-negative, aerobic, non-flagellated, rod-shaped bacterium, designated strain Lxc1T, was isolated from the surface of a marine red alga, Gracilaria sp., which was collected from the coastal regions in Jinjiang, Fujian Province, China. Colonies of the strain were orange-yellow, circular and smooth. The 16S rRNA gene of strain Lxc1T had maximum sequence similarity with Lacinutrix himadriensis E4 9aT (97.1 %), followed by Lacinutrix jangbogonensis PAMC 27137T, Lacinutrix copepodicola DJ3T, Lacinutrix algicola AKS293T and Lacinutrix mariniflava AKS 432T (similarities < 96.4 %). Phylogenetic analysis showed strain Lxc1T formed a tight cluster with L. himadriensis E4-9aT and L. copepodicola DJ3T, but represented a novel lineage belonging to the genus Lacinutrix. The predominant fatty acids were iso-C15 : 1 G (18.3 %), iso-C15 : 0 (16.7 %), iso-C17 : 0 3-OH (10.6 %) and iso-C15 : 0 3-OH (8.6 %). Menaquinone-6 (MK-6) was the only respiratory quinone present. The DNA G+C content of strain Lxc1T was 31.7 mol%. Combining the results above, it was ascertained that strain Lxc1T represented a novel species of the genus Lacinutrix, for which the name Lacinutrix gracilariae sp. nov. is proposed. The type strain is Lxc1T ( = MCCC 1A01567T = KCTC 42808T). PMID- 26554357 TI - Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway. AB - Renal fibrosis is a main cause of end-stage renal disease. Clinically, there is no beneficial treatment that can effectively reverse the progressive loss of renal function. We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. In this study, we evaluated the effect of CHBP on renal fibrosis in an in vivo ischemia reperfusion injury (IRI) model and in vitro TGF-beta-stimulated tubular epithelial cells (TCMK-1 and HK-2) model. In the IRI in vivo model, mice were randomly divided into sham (sham operation), IR and IR + CHBP groups (n = 6). CHBP (8 nmol/kg) was administered intraperitoneally at the onset of reperfusion, and renal fibrosis was evaluated at 12 weeks post-reperfusion. Our results showed that CHBP markedly attenuated the IRI-induced deposition of collagen I and vimentin. In the in vitro model, CHBP reversed the TGF-beta-induced down regulation of E-cadherin and up-regulation of alpha-SMA and vimentin. Furthermore, CHBP inhibited the phosphorylation of Akt and Forkhead box O 3a (FoxO3a), whose anti-fibrotic effect could be reversed by the 3-phosphoinositide dependent kinase-1 (PI3K) inhibitor wortmannin as well as FoxO3a siRNA. These findings demonstrate that CHBP attenuates renal fibrosis and the epithelial mesenchymal transition of tubular cells, possibly through suppression of the PI3K/Akt pathway and thereby the inhibition FoxO3a activity. PMID- 26554358 TI - Mapping the role of structural and interpersonal violence in the lives of women: implications for public health interventions and policy. AB - BACKGROUND: Research on interpersonal violence towards women has commonly focused on individual or proximate-level determinants associated with violent acts ignores the roles of larger structural systems that shape interpersonal violence. Though this research has contributed to an understanding of the prevalence and consequences of violence towards women, it ignores how patterns of violence are connected to social systems and social institutions. METHODS: In this paper, we discuss the findings from a scoping review that examined: 1) how structural and symbolic violence contributes to interpersonal violence against women; and 2) the relationships between the social determinants of health and interpersonal violence against women. We used concept mapping to identify what was reported on the relationships among individual-level characteristics and population-level influence on gender-based violence against women and the consequences for women's health. Institutional ethics review was not required for this scoping review since there was no involvement or contact with human subjects. RESULTS: The different forms of violence-symbolic, structural and interpersonal-are not mutually exclusive, rather they relate to one another as they manifest in the lives of women. Structural violence is marked by deeply unequal access to the determinants of health (e.g., housing, good quality health care, and unemployment), which then create conditions where interpersonal violence can happen and which shape gendered forms of violence for women in vulnerable social positions. Our web of causation illustrates how structural factors can have negative impacts on the social determinants of health and increases the risk for interpersonal violence among women. CONCLUSION: Public health policy responses to violence against women should move beyond individual-level approaches to violence, to consider how structural and interpersonal level violence and power relations shape the 'lived experiences' of violence for women. PMID- 26554359 TI - Non-canonical Activation of Akt in Serum-Stimulated Fibroblasts, Revealed by Comparative Modeling of Pathway Dynamics. AB - The dynamic behaviors of signaling pathways can provide clues to pathway mechanisms. In cancer cells, excessive phosphorylation and activation of the Akt pathway is responsible for cell survival advantages. In normal cells, serum stimulation causes brief peaks of extremely high Akt phosphorylation before reaching a moderate steady-state. Previous modeling assumed this peak and decline behavior (i.e., "overshoot") was due to receptor internalization. In this work, we modeled the dynamics of the overshoot as a tool for gaining insight into Akt pathway function. We built an ordinary differential equation (ODE) model describing pathway activation immediately upstream of Akt phosphorylation at Thr308 (Aktp308). The model was fit to experimental measurements of Aktp308, total Akt, and phosphatidylinositol (3,4,5)-trisphosphate (PIP3), from mouse embryonic fibroblasts with serum stimulation. The canonical Akt activation model (the null hypothesis) was unable to recapitulate the observed delay between the peak of PIP3 (at 2 minutes), and the peak of Aktp308 (at 30-60 minutes). From this we conclude that the peak and decline behavior of Aktp308 is not caused by PIP3 dynamics. Models for alternative hypotheses were constructed by allowing an arbitrary dynamic curve to perturb each of 5 steps of the pathway. All 5 of the alternative models could reproduce the observed delay. To distinguish among the alternatives, simulations suggested which species and timepoints would show strong differences. Time-series experiments with membrane fractionation and PI3K inhibition were performed, and incompatible hypotheses were excluded. We conclude that the peak and decline behavior of Aktp308 is caused by a non-canonical effect that retains Akt at the membrane, and not by receptor internalization. Furthermore, we provide a novel spline-based method for simulating the network implications of an unknown effect, and we demonstrate a process of hypothesis management for guiding efficient experiments. PMID- 26554361 TI - Patterns of Welfare Attitudes in the Australian Population. AB - The study of community attitudes toward welfare and welfare recipients is an area of increasing interest. This is not only because negative attitudes can lead to stigmatization and discrimination, but because of the relevance of social attitudes to policy decisions. We quantify the attitudes toward welfare in the Australian population using attitude data from a nationally representative survey (N = 3243). Although there was broad support for the social welfare system, negative attitudes are held toward those who receive welfare benefits. Using canonical correlation analysis we identify multivariate associations between welfare attitudes and respondent demographic characteristics. A primary attitudinal dimension of welfare positivity was found amongst those with higher levels of education, life instability, and personal exposure to the welfare system. Other patterns of negative welfare attitudes appeared to be motivated by beliefs that the respondent's personal circumstances indicate their deservingness. Moreover, a previously unidentified and unconsidered subset of respondents was identified. This group had positive attitudes toward receiving government benefits despite having no recent experience of welfare. They did, however, possess many of the characteristics that frequently lead to welfare receipt. These results provide insights into not only how attitudinal patterns segment across the population, but are of relevance to policy makers considering how to align welfare reform with community attitudes. PMID- 26554360 TI - Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial. AB - BACKGROUND: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans. METHODS/DESIGN: Patients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo controlled, double-blind, crossover study. The experimental days take place 6-8 weeks after surgery, time-points at which patients are expected to be almost pain free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276). DISCUSSION: We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies. TRIAL REGISTRATION NUMBER: EUDRACT: 2015-000793-36 (Registration date: 16 February 2015) Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014). PMID- 26554363 TI - Neuroscience(s): What is in the name? PMID- 26554362 TI - Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia. AB - Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2 relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles. PMID- 26554364 TI - Predictors of early or late treatment seeking in patients with social anxiety disorder. AB - BACKGROUND: Social anxiety disorder (SAD) is common in the general population and usually begins at an early age. It is well established that patients with SAD rarely seek treatment, and their first treatment contact usually takes many years after onset. The aim of this study was to determine the predictors of early and late treatment seeking in patients with SAD. METHODS: This study enrolled 180 patients with generalized SAD. The mean and median durations between the emergence of SAD and first treatment contact were 15 and 14 years, respectively. Multiple linear regression with the backward elimination method was applied to assess the factors that affect the amount of time between occurrence of the disorder and first treatment contact. RESULTS: Older age, earlier onset of SAD, and lower level of education were associated with late treatment seeking, whereas earlier onset of comorbid major depressive episodes and lifetime history of comorbid obsessive-compulsive disorder were associated with earlier treatment seeking. CONCLUSIONS: Age of onset, comorbid psychiatric conditions, and level of education are associated with the timing of treatment seeking in patients with SAD. It is important to try to change the common perception that SAD is a personality trait rather than a psychiatric disorder. PMID- 26554365 TI - Racial differences in antipsychotic use: Claims database analysis of Medicaid insured patients with schizophrenia. AB - BACKGROUND: Database analyses have indicated that medical treatment for schizophrenia varies among racial groups. This study assessed antipsychotic use and healthcare utilization across races in Medicaid-insured patients with schizophrenia. METHODS: A Medicaid database of inpatient/outpatient medical claims and outpatient prescription claims for more than 28 million enrollees in 11 geographically diverse states was analyzed. The primary outcome, racial differences in antipsychotic use in 2012, was examined in 5 multivariable logistic regression models: (1) any antipsychotic, (2) first-generation (FG) long acting injectables (LAIs), (3) FG oral antipsychotics, (4) second-generation (SG) LAIs, and (5) SG oral antipsychotics. RESULTS: Odds ratios and adjusted predicted probabilities were comparable for any antipsychotic use between black and white patients. Black patients were less likely to receive SG oral antipsychotics (P < .001) and more likely to receive SG or FG LAIs (P = .001 and P < .001, respectively) and FG oral antipsychotics (P = .003) vs white patients. Further, black patients had a higher mean number of emergency room visits (P < .001) and a lower mean number of hospitalizations (P < .05) vs white patients; the mean number of physician visits was comparable. CONCLUSIONS: Disparities in antipsychotic use and healthcare utilization across races in patients with schizophrenia warrant further investigation and elimination of these disparities should be a national goal. PMID- 26554366 TI - The risk of suicide after clozapine discontinuation: Cause for concern. AB - BACKGROUND: Clozapine is a second-generation antipsychotic that has been shown to reduce suicidal ideation and suicidal behaviors in patients with schizophrenia. However, it is underutilized because of its serious side effects. METHODS: We describe 3 patients with a history of suicide ideation and attempts who were successfully treated and maintained in the community without suicidal tendencies while taking clozapine. All 3 patients, men in their 20s, discontinued clozapine because of side effects and subsequently committed suicide. We also review the literature on clozapine's effects on suicidality. RESULTS: In these 3 cases, suicide followed abrupt discontinuation of clozapine or transition to another antipsychotic. CONCLUSIONS: This case series is the first of its kind to document the risk of suicide when clozapine is discontinued. The decision to discontinue clozapine should be made carefully, especially because clozapine is considered the treatment of last resort for patients with treatment-resistant schizophrenia and suicidal ideation. We stress the importance of minimizing the risk of abrupt clozapine discontinuation and recommend further evaluation of suicide ideation and attempts when clozapine is discontinued. PMID- 26554367 TI - Clinical and cognitive correlates of young adult at-risk gamblers with and without depression. AB - BACKGROUND: Depression is commonly found among young adults who have problems with gambling. Although depression and gambling frequently co-occur, it is unclear whether this relationship has clinical or cognitive importance. METHODS: The study analyzed 215 young adults (age 18 to 29) with "at-risk" gambling behavior. Scores on the Mini International Neuropsychiatric Interview were used to assess lifetime major depressive disorder. The participants were categorized by 2 groups: those with (81 [37.7%]) and those without (134 [62.3%]) depressive symptoms. The groups were compared using various measures assessing gambling severity, quality of life, comorbidity, and psychosocial dysfunction, as well as various cognitive tasks assessing impulsivity and working memory. RESULTS: Participants with depression who gambled had significantly worse gambling urges and behaviors. In addition, they reported significantly higher rates of anxiety (P < .001), suicidality (P < .001), alcohol (P = .036) and substance dependence (P = .009), compulsive buying (P = .004), and lower quality of life (P = .007). The depressed participants also demonstrated significantly greater impairments on cognitive tasks assessing spatial working memory. CONCLUSIONS: This research suggests that at-risk gamblers with depression differ clinically and cognitively from at-risk gamblers without depressive symptoms. These findings may have implications for treatment interventions. PMID- 26554368 TI - Psychometric properties of the Self-Report Wender-Reimherr Adult Attention Deficit Disorder Scale. AB - BACKGROUND: The Self-Report Wender-Reimherr Adult Attention Deficit Disorder Scale (SR-WRAADDS) assesses the same 7 attention-deficit/ hyperactivity disorder (ADHD) domains as the interviewer-administered WRAADDS. METHODS: A normative sample was recruited, and additional participants came from trials involving ADHD, anxiety, or depression. Using the investigator-administered WRAADDS, participants in the ADHD sample were classified as ADHD inattentive presentation or ADHD emotional dysregulation presentation. RESULTS: In the ADHD sample, the SR WRAADDS correlated with the investigator-rated version WRAADDS (P < .001). In comparing adults with ADHD with normal controls, all SR-WRAADDS domains demonstrated discriminate validity (P < .001); a cut point was identified yielding sensitivity of 97% and specificity of 89%. In comparison, in screening for ADHD in depression or anxiety disorders, sensitivity was 87% and specificity, 49%. Internal consistency was satisfactory (Cronbach alpha = 0.78; split-half reliability r = 0.92). Factor analysis yielded a 2-factor solution: one reflected emotional dysregulation; the other, inattention and disorganization. Detecting ADHD emotional dysregulation presentation within the ADHD sample, as the "disorder-of-interest," SR-WRAADDS and the investigator-rated WRAADDS agreement was 72% (sensitivity, 87%; specificity, 49%). The SR-WRAADDS detected a methylphenidate vs placebo treatment effect (P < .001). CONCLUSIONS: The psychometric properties of the SR-WRAADDS support its use in research and clinical practice. Emotional domains are integral to its assessment of adult ADHD. PMID- 26554369 TI - Rapid adipose deposition with mood disorders. AB - BACKGROUND: Persons with bipolar disorder represent a high-risk group for obesity, but little is known about the time course by which weight gain occurs in bipolar disorder. METHODS: We prospectively studied changes in fat distribution using dual-energy x-ray absorptiometry in relationship to medication exposure and mood symptom burden in 36 participants with bipolar disorder. We assessed the relationship between prior medication exposure and course of illness with adiposity measures at baseline (N = 36) and at 6-month follow-up (N = 22). RESULTS: At baseline, greater adiposity was associated with advanced age and female sex, not retrospectively assessed symptom course or medication exposure (past 2 years). Over 6 months of prospective follow-up, participants developed greater adiposity (fat mass index +0.82 kg/m(2), P = .007; visceral fat area +8.6 cm(2), P = .02; total percent fat +1.6%, P = .02). Manic symptomatology, not antipsychotic exposure, was related to the increased adiposity. CONCLUSIONS: Acute exacerbations of mood disorders appear to represent high-risk periods for adipose deposition. Obesity prevention efforts may be necessary during acute exacerbations. PMID- 26554370 TI - A meta-analysis of placebo-controlled trials of omega-3 fatty acid augmentation in schizophrenia: Possible stage-specific effects. AB - BACKGROUND: Omega-3 fatty acids have shown promise as an adjunctive treatment for schizophrenia. However, efficacy across studies has been inconsistent. We conducted a meta-analysis of published controlled studies with the goal of detecting different efficacy profiles at various stages of schizophrenia. METHODS: An online search was conducted for randomized, double-blind, placebo controlled clinical trials, and a meta-analysis was conducted. RESULTS: Ten studies met the criteria for inclusion. Among patients in the prodromal phase of schizophrenia, omega-3 supplementation reduced psychotic symptom severity and lowered conversion rates to first-episode psychosis. In patients with first episode schizophrenia, omega-3 decreased nonpsychotic symptoms, required lower antipsychotic medication dosages, and improved early treatment response rates. Omega-3 had mixed results in patients with stable chronic schizophrenia, with only some patients experiencing significant benefits. Among patients with chronic schizophrenia, use of omega-3 fatty acids both by those experiencing acute exacerbations and those who had discontinued antipsychotic medications resulted in worsening of psychotic symptoms. CONCLUSIONS: The data suggest that omega-3 fatty acids may be efficacious in reducing clinical symptoms for patients in the earlier stages of schizophrenia (prodrome and first episode), while producing mixed results for patients in the chronic stages. Based on these results, omega-3 fatty acids would not be recommended for acute exacerbations in patients with chronic schizophrenia nor for relapse prevention after discontinuation of antipsychotics. PMID- 26554371 TI - Making psychotherapy for borderline personality disorder accessible. AB - BACKGROUND: Psychotherapies specifically designed for borderline personality disorder (BPD) are the most effective form of treatment for this population, but these modalities are not easily accessible. METHOD: Narrative review. RESULTS: Although research shows that such therapies are effective, the best-known methods are lengthy, expensive, and difficult for patients to access. CONCLUSIONS: This review recommends that interventions for patients with BPD should be briefer, less costly, and more accessible. PMID- 26554372 TI - Topiramate in dextromethorphan abuse. PMID- 26554373 TI - Rage outbursts in adult obsessive-compulsive disorder. PMID- 26554375 TI - A case of nicotine overdose-induced seizure on an inpatient psychiatric unit. PMID- 26554376 TI - A Qualitative Study of Environmental Factors Important for Physical Activity in Rural Adults. AB - PURPOSE: Despite increasing evidence that the physical environment impacts on physical activity among urban-dwellers, little attention has been devoted to understanding this relationship in rural populations. Work in this area is further hindered by a lack of environmental measures specifically designed for rural settings. This qualitative study aimed to explore the salience of urban physical activity environment constructs among rural adults. METHODS: In 2011, 49 rural men and women from three distinct areas (coastal, animal-based farming, forestry/plant-based farming) of rural Tasmania, Australia, were purposively recruited to participate in semi-structured interviews. Interviews explored features of the built and social environment commonly examined in studies of urban adults, including functional characteristics (eg, lighting, footpaths, roads/verges), road and personal safety, availability and accessibility of places to be active, destinations, and aesthetics. Interviews were recorded, transcribed verbatim and analysed using a content-thematic approach using QSR NVivo software. FINDINGS: While some urban environmental constructs were salient to these rural adults, such as availability of and accessibility to places to be active, some constructs were operationalised differently, such as road safety (where large trucks and winding roads rather than traffic density was of concern), or were not considered relevant (eg, personal safety related to crime, availability of walkable destinations, aesthetics). CONCLUSIONS: The measurement of the physical environment in rural populations may require reconsideration and/or modification to ensure salience and appropriate quantification of associations with physical activity in future studies. PMID- 26554377 TI - Down-Regulation of Nucleolar and Spindle-Associated Protein 1 (NUSAP1) Expression Suppresses Tumor and Cell Proliferation and Enhances Anti-Tumor Effect of Paclitaxel in Oral Squamous Cell Carcinoma. AB - BACKGROUND: Nucleolar and spindle-associated protein 1 (NUSAP1) is an important mitotic regulator. In addition to its crucial function in mitosis, NUSAP1 has recently received attention due to the interesting roles in carcinogenesis. The aim of this study was to reveal functional mechanisms of NUSAP1 in oral squamous cell carcinoma (OSCC). METHODS: mRNA and protein expression levels of NUSAP1 in 9 OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. The correlation between the NUSAP1 expression profile and the clinicopathological factors was evaluated by immunohistochemistry (IHC) in clinical OSCC samples (n = 70). The NUSAP1 knockdown cells were established with short hairpin RNA (shRNA) in OSCC cells, and functional assays were performed using these cells. In addition to the evaluation of cellular proliferation and cell cycle, we also investigated the potential role of NUSAP1 in paclitaxel (PTX)-induced cellular responses. RESULTS: mRNA and protein expression of NUSAP1 were significantly up-regulated in OSCC derived cells compared with human normal oral keratinocytes (P < 0.05). IHC revealed that NUSAP-1 expression is closely associated with primary advanced T stage (P<0.05). Suppression of NUSAP1 expression levels led to significant (P < 0.05) inhibition of cellular proliferation. Furthermore, apoptosis induced by PTX was enhanced in NUSAP1 knockdown OSCC cells. CONCLUSIONS: NUSAP1 may be a crucial biomarker for OSCC. Moreover, down-regulated NUSAP1 expression suppresses tumor proliferation and also enhances anti-tumor effect of PTX by activating apoptotic pathways. Thus, the present study strongly suggests that regulating NUSAP1 expression should contribute to the therapy for OSCC. PMID- 26554378 TI - Evaluation of Salivary Secretor Status of Blood Group Antigens in Patients with Oral Lichen Planus. AB - OBJECTIVE: To investigate the relationship between secretion or nonsecretion of blood group antigens into the saliva and oral lichen planus (OLP). SUBJECTS AND METHODS: In this study, 30 patients (women: 22, men: 8) with OLP were examined as the case group and 30 subjects without OLP matched for age and gender as the control group. Diagnosis of OLP was confirmed by clinical and histopathological examinations according to WHO criteria. The control group was randomly selected from healthy individuals without pathological oral changes seeking dental treatment. In both groups, blood group type was determined by hemagglutination, and unstimulated saliva was collected using the Navazesh technique. Establishment of salivary secretor status was carried out using the Wiener agglutination test. The data were analyzed using a Chi2 test, Fisher's exact test, and logistic regression. RESULTS: The patients with OLP (cases), including 22 (36.7%) women and 8 (13.3%) men with a mean age of 51 +/- 14.16 years, were compared with healthy subjects (controls), comprised of 25 (41.7%) women and 5 (8.3%) men with a mean age of 50.7 +/- 13.56 years. A large majority of the people examined in both groups were secretors of blood group A. On the other hand, most OLP patients were blood group B. In the case group, 25 subjects (84.4%) were secretors and 5 (16.6%) were nonsecretors. In the control group, 24 subjects (80.0%) were secretors and 6 (20.0%) were nonsecretors. There was no significant difference between the case and control groups for secretor status (p = 0.73). CONCLUSION: The present study did not indicate a significant difference in salivary secretor status between OLP patients compared to controls. PMID- 26554379 TI - The Neuropilin-1 Inhibitor, ATWLPPR Peptide, Prevents Experimental Diabetes Induced Retinal Injury by Preserving Vascular Integrity and Decreasing Oxidative Stress. AB - Neuropilin-1 (NRP-1) is a transmembrane glycoprotein. As a VEGF co-receptor, NRP1 significantly enhances VEGFR2 signaling and promotes vascular permeability and migration. The purpose of this study was to evaluate the effects of an NRP-1 inhibitor, ATWLPPR peptide, on the early stages of diabetic retinopathy. Eight week-old male C57BL/6 mice were divided into three groups: a Normal group, a Diabetes (DB) ATWLPPR treatment group and a DB saline group. Electroretinography (ERG), fundus fluorescence angiography (FFA) and leukostasis were examined to evaluate the retinal injury induced by diabetes at the end of the fifth week after STZ injection. Occludin expression and extravasation of albumin were measured to determine the extent of vascular injury. The oxidative stress level and the levels of inflammation-associated proteins were also assayed. The results indicated that treatment with ATWLPPR prevents the abnormal condition of ERG (amplitudes of b-wave decreased and implicit time increased) and vascular injury (occludin degradation and increase in extravasated albumin). These effects were associated with a reduction in the oxidase stress level and the expression of VEGF, GFAP, and ICAM-1. We conclude that ATWLPPR, an NRP-1 inhibitor, may reduce the early retinal damage induced by diabetes by preserving vascular integrity and decreasing the oxidative stress level. Blockade of NRP-1 may be a new therapeutic strategy for the early stages of DR. PMID- 26554380 TI - Mutational Profiling Can Establish Clonal or Independent Origin in Synchronous Bilateral Breast and Other Tumors. AB - BACKGROUND: Synchronous tumors can be independent primary tumors or a primary metastatic (clonal) pair, which may have clinical implications. Mutational profiling of tumor DNA is increasingly common in the clinic. We investigated whether mutational profiling can distinguish independent from clonal tumors in breast and other cancers, using a carefully defined test based on the Clonal Likelihood Score (CLS = 100 x # shared high confidence (HC) mutations/ # total HC mutations). METHODS: Statistical properties of a formal test using the CLS were investigated. A high CLS is evidence in favor of clonality; the test is implemented as a one-sided binomial test of proportions. Test parameters were empirically determined using 16,422 independent breast tumor pairs and 15 primary metastatic tumor pairs from 10 cancer types using The Cancer Genome Atlas. RESULTS: We validated performance of the test with its established parameters, using five published data sets comprising 15,758 known independent tumor pairs (maximum CLS = 4.1%, minimum p-value = 0.48) and 283 known tumor clonal pairs (minimum CLS 13%, maximum p-value <0.01), across renal cell, testicular, and colorectal cancer. The CLS test correctly classified all validation samples but one, which it appears may have been incorrectly classified in the published data. As proof-of-concept we then applied the CLS test to two new cases of invasive synchronous bilateral breast cancer at our institution, each with one hormone receptor positive (ER+/PR+/HER2-) lobular and one triple negative ductal carcinoma. High confidence mutations were identified by exome sequencing and results were validated using deep targeted sequencing. The first tumor pair had CLS of 81% (p-value < 10-15), supporting clonality. In the second pair, no common mutations of 184 variants were validated (p-value >0.99), supporting independence. A plausible molecular mechanism for the shift from hormone receptor positive to triple negative was identified in the clonal pair. CONCLUSION: We have developed the statistical properties of a carefully defined Clonal Likelihood Score test from mutational profiling of tumor DNA. Under identified conditions, the test appears to reliably distinguish between synchronous tumors of clonal and of independent origin in several cancer types. This approach may have scientific and clinical utility. PMID- 26554381 TI - Sea-level feedback lowers projections of future Antarctic Ice-Sheet mass loss. AB - The stability of marine sectors of the Antarctic Ice Sheet (AIS) in a warming climate has been identified as the largest source of uncertainty in projections of future sea-level rise. Sea-level fall near the grounding line of a retreating marine ice sheet has a stabilizing influence on the ice sheets, and previous studies have established the importance of this feedback on ice age AIS evolution. Here we use a coupled ice sheet-sea-level model to investigate the impact of the feedback mechanism on future AIS retreat over centennial and millennial timescales for a range of emission scenarios. We show that the combination of bedrock uplift and sea-surface drop associated with ice-sheet retreat significantly reduces AIS mass loss relative to a simulation without these effects included. Sensitivity analyses show that the stabilization tends to be greatest for lower emission scenarios and Earth models characterized by a thin elastic lithosphere and low-viscosity upper mantle, as is the case for West Antarctica. PMID- 26554382 TI - Serum Lipids and Breast Cancer Risk: A Meta-Analysis of Prospective Cohort Studies. AB - PURPOSE: Epidemiologic studies exploring causal associations between serum lipids and breast cancer risk have reported contradictory results. We conducted a meta analysis of prospective cohort studies to evaluate these associations. METHODS: Relevant studies were identified by searching PubMed and EMBASE through April 2015. We included prospective cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of specific lipid components (i.e., total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) with breast cancer risk. Either a fixed- or a random-effects model was used to calculate pooled RRs. RESULTS: Fifteen prospective cohort studies involving 1,189,635 participants and 23,369 breast cancer cases were included in the meta-analysis. The pooled RRs of breast cancer for the highest versus lowest categories were 0.96 (95% CI: 0.86-1.07) for TC, 0.92 (95% CI: 0.73 1.16) for HDL-C, 0.90 (95% CI: 0.77-1.06) for LDL-C, and 0.93 (95% CI: 0.86-1.00) for TG. Notably, for HDL-C, a significant reduction of breast cancer risk was observed among postmenopausal women (RR = 0.77, 95% CI: 0.64-0.93) but not among premenopausal women. Similar trends of the associations were observed in the dose response analysis. CONCLUSIONS: Our findings suggest that serum levels of TG but not TC and LDL-C may be inversely associated with breast cancer risk. Serum HDL-C may also protect against breast carcinogenesis among postmenopausal women. PMID- 26554384 TI - General health and state anxiety in patients recovering from colorectal cancer surgery. AB - AIM: To describe and compare general health and state anxiety before surgery and up to 6 months after surgery in patients with colorectal cancer undergoing elective rectal resection, abdominoperineal resection or colonic resection in an enhanced recovery context. BACKGROUND: Little is known about patient-reported health and anxiety after colorectal cancer surgery in an enhanced recovery context. DESIGN: A prospective cohort study. METHODS: Data were collected from October 2011-February 2013. The questionnaires - EuroQol 5-Dimensions 3-Levels and State-Trait Anxiety Inventory - were answered before surgery, at discharge and 1 and 6 months after surgery. Data were analysed using inferential statistics to describe differences between groups of patients (Kruskal-Wallis test) and between assessments within groups (Friedman's anova). RESULTS: Patients (N = 105), divided into three groups based on surgical procedure, showed a high health index and a low state anxiety in all assessments without differences between the groups. Patients considered for abdominoperineal resection rated their pre operative health as significantly higher than patients after rectal and colonic resections did. Within groups, patients recovering from abdominoperineal resection and rectal resection deteriorated significantly in health index 1 month after surgery. However, after 6 months they had improved again. After colonic resection, patients improved significantly in self-rated health and anxiety 1 month after surgery with no further discernible improvement after 6 months. CONCLUSION: The study showed that patients generally had a high level of health and a low level of anxiety throughout the study period. Only a few differences occurred between assessments within groups. PMID- 26554383 TI - Evaluation of Xpert(r) MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial. AB - OBJECTIVE: Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert(r) MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. METHODS: We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009 2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's chi2 test; and Wilson's score method to calculate sensitivity and specificity. RESULTS: 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6 100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. CONCLUSION: Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum and gastric lavage to justify selection of one sampling method over the other, in young children with suspected pulmonary TB. TRIAL REGISTRATION: ClinicalTrials.gov NCT00953927. PMID- 26554385 TI - Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m. AB - OBJECTIVE: We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. METHODS: The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. RESULTS: The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. CONCLUSIONS: Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS. PMID- 26554386 TI - Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area. AB - RATIONALE: Repeated administration of methamphetamine (Meth) induces behavioral sensitization which is characterized by a progressive increase in locomotor response after each injection. Previous studies have shown that Mu opioid receptors (MORs) can regulate Meth-mediated behavioral sensitization. However, the reported interactions are controversial; systemic activation of MORs either enhanced or suppressed Meth sensitization. It is possible that alteration of Meth sensitization after systemic administration of MOR ligands reflects the sum of distinct MOR reactions in multiple brain regions. OBJECTIVES: The purpose of the present study was to examine the actions of MORs on Meth sensitization after regionally selective overexpression of human MOR through an AAV6-based gene delivery system. METHOD: We demonstrated that adeno-associated virus (AAV)-MOR increased MOR immunoreactivity and binding in vitro. AAV-MOR or AAV-green fluorescent protein (GFP) was injected into the nucleus accumbens (NAc) or ventral tegmental area (VTA) of adult mice. Two weeks after viral infection, animals received Meth or saline for five consecutive days. Locomotor behavior and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) level were determined. RESULTS: Repeated administration of Meth progressively increased locomotor activity; this sensitization reaction was attenuated by intra-NAc AAV MOR microinjections. Infusion of AAV-MOR to VTA enhanced Meth sensitization. AAV MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. CONCLUSION: Our data suggest a differential modulation of Meth sensitization by overexpression of MOR in NAc and VTA. Regional manipulation of MOR expression through AAV may be a novel approach to control Meth abuse and psychomimetic activity. PMID- 26554387 TI - Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice. AB - RATIONALE: Mesolimbic dopamine (DA) regulates behavioral activation and effort related decision-making in motivated behaviors. Mesolimbic DA D2 receptors are co localized with adenosine A2A receptors, and they interact in an antagonistic manner. OBJECTIVES: A T-maze task was developed to assess dopaminergic involvement in preference between a reinforcer that involves vigorous voluntary activity (running wheel) and a reinforcer that requires minimal behavioral activation (sucrose pellets). Haloperidol (D2 antagonist) was administered to adenosine A2A receptor knockout (A2AKO) and wild-type (WT) littermate controls to assess the involvement of these two receptors in the selection of running wheel activity versus sucrose consumption. RESULTS: Under control conditions, mice spent more time running and less time eating. In WT mice, haloperidol reduced time running but actually increased time-consuming sucrose. However, A2AKO mice did not show the haloperidol-induced shift from running wheel activity to sucrose intake. Prefeeding reduced sucrose consumption in the T-maze in both strains, indicating that this paradigm is sensitive to motivational devaluation. Haloperidol increased c-Fos immunoreactivity in anterior cingulate cortex (ACg) and nucleus accumbens (Acb) core of WT but not KO mice. CONCLUSIONS: These results indicate that after DA antagonism, the preference for vigorous physical activity is reduced, while palatable food selection increases. Adenosine A2A receptor deletion provides resistance to these effects of D2 receptor antagonism. These two receptors in Acb core and ACg seem to be involved in the regulation of the intrinsic reinforcing characteristics of voluntary exercise but not in the regulation of the primary reinforcing characteristics of palatable sedentary reinforcers. PMID- 26554388 TI - Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum. AB - RATIONALE: Studies in human and non-human primates demonstrate that social status is an important determinant of cocaine reinforcement. However, it is unclear whether social rank is associated with other traits that also predispose to addiction and whether social status similarly predicts cocaine self administration in rats. OBJECTIVES: The objective of this study is to investigate whether social ranking assessed using a resource competition task affects (i) the acquisition, maintenance and reinstatement of cocaine self-administration; (ii) the dopaminergic markers in the striatum; and (iii) the expression of ancillary traits for addiction. METHODS: Social ranking was determined in group-housed rats based upon drinking times during competition for a highly palatable liquid. Rats were then evaluated for cocaine self-administration and cue-induced drug reinstatement or individual levels of impulsivity, anxiety and novelty-induced locomotor activity. Finally, dopamine content, dopamine transporter (DAT) and dopamine D2/D3 (D2/3) receptor binding were measured postmortem in the dorsal and ventral striatum. RESULTS: Rats deemed socially dominant showed enhanced novelty reactivity but were neither more impulsive nor anxious compared with subordinate rats. Dominant rats additionally maintained higher rates of cocaine self administration but showed no differences in the acquisition, extinction and reinstatement of this behaviour. D2/3 binding was elevated in the nucleus accumbens shell and dorsal striatum of dominant rats when compared to subordinate rats, and was accompanied by elevated DAT and reduced dopamine content in the nucleus accumbens shell. CONCLUSIONS: These findings show that social hierarchy influences the rate of self-administered cocaine but not anxiety or impulsivity in rats. Similar to non-human primates, these effects may be mediated by striatal dopaminergic systems. PMID- 26554389 TI - Response to novelty and cocaine stimulant effects: lack of stability across environments in female Swiss mice. AB - RATIONALE: In humans, novelty/sensation seeking is seen as a personality trait with a positive relationship with addiction vulnerability. In animal studies, one of the standard procedures to model novelty seeking is the "response to novelty," i.e., the levels of locomotor activity in a new environment. In rodents, a positive correlation was demonstrated between the response to novelty and several effects of drugs, especially the locomotor stimulant effects of cocaine. OBJECTIVES: The present study was designed to test in mice whether the response to novelty is stable across environments and whether its relationship with the stimulant effects of cocaine is altered by environmental changes. Experiment 1 assessed the responses to novelty of the same mice in two different novel environments. Experiment 2 tested the correlation between response to novelty and acute stimulant effects of cocaine recorded in two distinct environments. RESULTS: The results show a weak correlation only during the first 5 min of the session between the responses to novelty measured in two distinct environments. Experiment 2 demonstrates that novelty responses and stimulant effects of cocaine are positively correlated only when both behavioral responses are measured in the same environment. In contrast, the relationship between response to novelty and acute stimulant effects of cocaine is completely lost when the behavioral responses are recorded in two different environments. CONCLUSIONS: The present results question the usual interpretation of the correlation between the response to novelty and the stimulant effects of cocaine as reflecting a relationship between two underlying individual stable characteristics. PMID- 26554391 TI - Immunostimulatory effect of tetanus toxoid loaded chitosan nanoparticles following microneedles assisted immunization. AB - The present study investigated potential of tetanus toxoid loaded chitosan nanoparticles (TT-Ch-NPs) following bare topical and microneedles assisted immunization. The TT-Ch-NPs were prepared by ionotropic gelation method using poly(sodium-4-styrene sulfonate) (PSS) as crosslinking agent which exhibited ~208 nm size and ~99% entrapment efficiency. The manufacturing process did not have any detrimental effect on integrity and conformation of antigen. The in vitro analysis demonstrated higher skin penetration following microneedles assisted immunization. In vivo immunization studies exhibited that TT-Ch-NPs delivered through microneedles induced comparable IgG and IgG1 titer, yet higher IgG2a titer than commercial TT vaccine. Similarly, microneedles assisted administration of TT-Ch-NPs generated higher Th1 cytokines, albeit no significant alteration in Th2 cytokines levels than commercial TT vaccine. In conclusion, microneedles assisted administration of TT-Ch-NPs especially via hollow microneedles (HMN) could be considered as best preferred route for immunization due to induction of more balanced Th1/Th2 biased immune response. From the Clinical Editor: The use of skin as a route for vaccination has been a clinically important topic for some time. In this article, the authors investigated the efficacy of both solid microneedles and hollow microneedles as methods for topical delivery of tetanus toixoid. The positive finding in the experiments could provide a better method for vaccination in the clinical setting in the future. PMID- 26554390 TI - A novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improves Abeta25-35-impaired mouse cognitive function. AB - RATIONALE: The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy. OBJECTIVES: We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Abeta25-35-injected mice, and the potential mechanisms. METHODS: AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Abeta25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR 1693. Mice were orally administrated with SCR-1693 once daily after an Abeta25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12. RESULTS: SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR 1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR 1693 was more effective than donepezil and memantine in preventing Abeta25-35 induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Abeta25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Abeta25-35-induced signal cascade in neurons. CONCLUSIONS: All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy. PMID- 26554392 TI - Nanomechanical and surface properties of rMSCs post-exposure to CAP treated UHMWPE wear particles. AB - Wear debris generated by ultra-high molecular weight polyethylene (UHMWPE) used in joint replacement devices has been of concern due to reductions of the implant longevity. Cold atmospheric plasma (CAP) has been used to improve the wear performance of UHMWPE. Our aim was to investigate the elastic and adhesive properties of rat mesenchymal stem cells (rMSCs), through AFM, after exposure to UHMWPE wear debris pre- and post-CAP treatment. The results indicated that the main changes in cell elasticity and spring constant of MSC exposed to wear particles occurred in the first 24 h of contact and the particle concentration from 0.5 to 50 mg/l did not play a significant role. For UHMWPE treated for 7.5 min, with progression of the wear simulation the results of the CAP treated samples were getting closer to the result of untreated samples; while with longer CAP treatment this was not observed. FROM THE CLINICAL EDITOR: Joint replacements are now common clinical practice. However, the use of ultra-high molecular weight polyethylene (UHMWPE) still poses a concern, due to the presence of wear debris. The authors here investigated the effects of wear debris after cold atmospheric plasma treatment on rat mesenchymal stem cells. The positive results provided new strategies in future design of joint replacement materials. PMID- 26554393 TI - Designing idiosyncratic hmPCL-siRNA nanoformulated capsules for silencing and cancer therapy. AB - In this work, we have designed a siRNA-nanoformulation with mesoporous polycaprolactone (hmPCL) for silencing and cancer therapy. Average hollow core size of hmPCL nanocapsules used for nanoformulation is ~180 nm with shell thickness of 10-20 nm and mesopore size of ~5-10nm in diameter. Idiosyncratic capsules are biocompatible which has been confirmed with normal lymphocyte, K562 leukaemia cancer cells and on HepG2/EGFP cancer cells. In 1mg of hmPCL capsules up to 400 ng of siRNA can be loaded. This nanoformulation enables to tune the dose dependent delivery up to ~93.25% (373 ng) siRNA during therapy. hmPCL-siRNA nanoformulation mediated siRNA transfection on HepG2 cancer cells has been investigated and exhibited 32% silencing activity within 24h of post transfection. Obtained results directed us that the hmPCL-siRNA nanoformulation could be an efficient tool in siRNA mediated therapy for knocking down the infected cells. FROM THE CLINICAL EDITOR: siRNA could be used in cancer therapy if naked nucleic acid could be transported using a suitable carrier. In this article, the authors developed a nano-carrier system using mesoporous polycaprolactone (hmPCL) and showed its efficacy in knocking down cancer cells. This approach may open another way of gene therapy. PMID- 26554394 TI - Spitz naevi and melanomas with similar dermoscopic patterns: can confocal microscopy differentiate? AB - BACKGROUND: Differentiating Spitz naevi from melanomas can be difficult both clinically and dermoscopically. Previous studies have reported the potential role of in vivo reflectance confocal microscopy (RCM) in increasing diagnostic accuracy. OBJECTIVES: To define RCM criteria that can differentiate 'false twins', namely Spitz naevi and melanomas sharing similar dermoscopic appearance. METHODS: Lesions histopathologically diagnosed as Spitz naevi or melanomas were retrospectively retrieved. They were selected to cover all dermoscopic types and were put into couples sharing similar aspects. Lesions were classified into three main dermoscopic categories: globular and starburst pattern, spitzoid with dotted vessels, and multicomponent or aspecific pattern. RESULTS: RCM findings revealed that striking cell pleomorphism within the epidermis, widespread atypical cells at the dermoepidermal junction and marked pleomorphism within nests were significantly associated with the diagnosis of melanoma, while spindled cells and peripheral clefting were found exclusively with and pathognomonic of Spitz naevi. Furthermore, the analysis of a dermoscopic subgroup highlights the importance of striking pleomorphism and spindled cells as clues to differentiate 'false twins' with globular or starburst patterns. CONCLUSIONS: The current study highlights the role of RCM in discriminating 'false twins' of Spitz naevi and melanomas for lesions showing starburst and globular patterns on dermoscopy, whereas RCM is not useful in the other dermoscopic subgroups. PMID- 26554395 TI - Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter Osteoarthritis Study. AB - OBJECTIVE: Pain sensitization is associated with pain severity in knee osteoarthritis (OA), but its cause in humans is not well understood. We examined whether inflammation, assessed as synovitis and effusion on magnetic resonance imaging (MRI), or mechanical load, assessed as bone marrow lesions (BMLs), was associated with sensitization in knee OA. METHODS: Subjects in the Multicenter Osteoarthritis Study, a National Institutes of Health-funded cohort of persons with or at risk of knee OA, underwent radiography and MRI of the knee, and standardized quantitative sensory testing (temporal summation and pressure pain threshold [PPT]) of the wrist and patellae at baseline and 2 years later. We examined the relation of synovitis, effusion, and BMLs to temporal summation and PPT cross-sectionally and longitudinally. RESULTS: There were 1,111 subjects in the study sample (mean age 67 years, mean body mass index 30 kg/m(2) , 62% female). Synovitis was associated with a significant decrease in PPT at the patella (i.e., more sensitized) over 2 years (adjusted beta -0.30 [95% confidence interval (95% CI) -0.52, -0.08]). Effusion was similarly associated with a decrease in PPT at the wrist (adjusted beta -0.24 [95% CI -0.41, -0.08]) and with risk of incident temporal summation at the patella (adjusted OR 1.54 [95% CI 1.01, 2.36]). BMLs were not associated with either quantitative sensory testing measure. CONCLUSION: Inflammation, as evidenced by synovitis or effusion, is associated with pain sensitization in knee OA. In contrast, BMLs do not appear to contribute to sensitization in knee OA. Early targeting of inflammation is a reasonable strategy to test for prevention of sensitization and through this, reduction of pain severity, in knee OA. PMID- 26554396 TI - In Vitro Model of Physiological and Pathological Blood Flow with Application to Investigations of Vascular Cell Remodeling. AB - Vascular disease is a common cause of death within the United States. Herein, we present a method to examine the contribution of flow dynamics towards vascular disease pathologies. Unhealthy arteries often present with wall stiffening, scarring, or partial stenosis which may all affect fluid flow rates, and the magnitude of pulsatile flow, or pulsatility index. Replication of various flow conditions is the result of tuning a flow pressure damping chamber downstream of a blood pump. Introduction of air within a closed flow system allows for a compressible medium to absorb pulsatile pressure from the pump, and therefore vary the pulsatility index. The method described herein is simply reproduced, with highly controllable input, and easily measurable results. Some limitations are recreation of the complex physiological pulse waveform, which is only approximated by the system. Endothelial cells, smooth muscle cells, and fibroblasts are affected by the blood flow through the artery. The dynamic component of blood flow is determined by the cardiac output and arterial wall compliance. Vascular cell mechano-transduction of flow dynamics may trigger cytokine release and cross-talk between cell types within the artery. Co-culture of vascular cells is a more accurate picture reflecting cell-cell interaction on the blood vessel wall and vascular response to mechanical signaling. Contribution of flow dynamics, including the cell response to the dynamic and mean (or steady) components of flow, is therefore an important metric in determining disease pathology and treatment efficacy. Through introducing an in vitro co-culture model and pressure damping downstream of blood pump which produces simulated cardiac output, various arterial disease pathologies may be investigated. PMID- 26554397 TI - Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems. AB - Understanding and apprehension of the characteristics and circumstances in which mesenchymal stem cells (MSCs) affect and make alterations (enhance or reduce) to the growth of tumors and metastasis spread is pivotal, not only for reaching the possibility to employ MSCs as drug delivery systems, but also for making forward movement in the existing knowledge of involvement of major factors (tumor microenvironment, soluble signaling molecules, etc.) in the process of carcinogenesis. This capability is reliable because MSCs present a great basis for engineering and constructions of new systems to target cancers, intended to secrete therapeutic proteins in the tumor region, or for delivering of oncolytic viruses' directly at the tumor site (targeted chemotherapy with enzyme prodrug conversion or induction of tumor cell apoptosis). MSCs as a crucial segment of the tumor surroundings and their confirmed tumor tropism, are assumed to be an open gateway for the design of promising drug delivery systems. The presented paper reviews current publications in this fieldwork, searches out the most recent patents that were published after 2012 (WO2014066122, US20140017787, WO2015100268, US20150086515), and tries to present the current progress and future prospective on the design and development in anti-cancer drug delivery systems based on MSCs. PMID- 26554398 TI - Impact of gender and menopausal status on metabolic parameters in chronic hepatitis C infection. AB - Hepatitis C infection (HCV) and menopause are associated with insulin resistance (IR), and IR accelerates HCV-induced liver disease. The relationship between menopause and IR has not been studied in this population. This study aimed to assess the impact of menopause on IR and metabolic syndrome in HCV. One hundred and three (69 men, 16 premenopausal, 18 postmenopausal women) noncirrhotic, nondiabetic HCV-infected adults underwent IR measurement via steady-state plasma glucose during a 240-min insulin suppression test. Metabolic syndrome was defined by at least three of five standard laboratory/clinical criteria. The patient characteristics were as follows: mean age 48 years, waist circumference 94.4 +/- 12.4 cm and 37.9% Caucasian. SSPG was higher in postmenopausal than premenopausal women or men (mean difference 18, 95% CI -41 to 76 and 35, 95% CI -3 to 72 mg/dL; respectively). After adjusting for waist circumference, female gender, nonwhite race and triglycerides were positively associated and high-density lipoprotein negatively associated with steady-state plasma glucose. Compared to men, both pre (Coef 48, 95% CI 12-84) and postmenopausal women (Coef 49, 95% CI 17-82) had higher steady-state plasma glucose. Compared to premenopausal women, men (OR 2.0, 95% CI 0.38-10.2) and postmenopausal women (OR 2.9, 95% CI 0.46-18.8) had higher odds of metabolic syndrome, but this was statistically nonsignificant. Both liver inflammation (OR 7.9) and nonwhite race (OR 6.9) were associated with metabolic syndrome. We conclude that women are at inc-reased risk for IR in HCV. There may also be an increased risk of metabolic syndrome postmenopause. Along with lifestyle modification and weight loss, women with metabolic abnormalities represent an especially at-risk group warranting HCV treatment to prevent adverse metabolic outcomes. PMID- 26554399 TI - Assessment of nailfold capillaries with a handheld dermatoscope may discriminate the extent of organ involvement in patients with systemic sclerosis. AB - To investigate whether nailfold capillaroscopy (NFC) patterns assessed through an in-office handheld dermatoscope may reflect the extent of disease severity in systemic sclerosis (SSc). NFC patterns were evaluated with a non-contact, polarized light dermatoscope in 40 consecutive patients with SSc and graded in sequence as 0 = normal, 1 = early, 2 = active, or 3 = late patterns. Disease severity was measured according to a modified Medsger severity scale (MSS). For comparisons, patients were grouped in tertiles according to disease severity, and a numerical correlation between the NFC patterns and the composite MSS score was assessed. Twenty patients had normal or early NFC patterns, most of them (17 individuals, 85 %) having low to moderate disease severity. In contrast, 18 out of 20 (90 %) patients with active or late NFC patterns had moderate to high disease severity. Accordingly, patients with normal/early NFC patterns had a median MSS score of 4 (interquartile range (IQR), 3-5) as compared with 7 (4-8; P = 0.02) in those with active/late patterns. A Spearman's rho coefficient of 0.45 (95 % CI, 0.15-0.67; P = 0.003) was found between the graded scale of NFC patterns and the composite MSS score. A handheld dermatoscope is useful to visualize the NFC patterns in SSc patients, and it is efficient enough to reflect the extent of disease severity. PMID- 26554400 TI - Correction to 'Biophysics of protein evolution and evolutionary protein biophysics'. PMID- 26554402 TI - Persistent Pulmonary Hypertension of the Newborn with D-transposition of the Great Arteries: Management and Prognosis. AB - OBJECTIVE: There is a paucity of data on clinical correlates and outcomes of pulmonary hypertension (PH) in patients with D-transposition of the great arteries (D-TGA) in the era of inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Our objective was to compare clinical characteristics and outcomes of infants with D-TGA with and without PH, defined as hypoxemia that required iNO and/or ECMO. METHODS: We undertook a single-center retrospective chart review involving infants with gestational age >=32 weeks with D-TGA who, underwent arterial switch operation over a 12-year period. Demographic and clinical data, details of the repair and postoperative complications were abstracted. RESULTS: Our cohort (n = 93), 61 (66%) of whom were males, had a mean (SD) gestational age and birth weight of 38.7 (1.8) weeks and 3.2 (0.6) kg, respectively. PH requiring iNO and/or ECMO was noted in 20 (21.5%) infants. Infants with PH had significantly lower birth weight [2.8 (0.56) vs. 3.33 (0.61)] and gestational age [37.7 (2.1) vs. 38.9 (1.7)] than those without PH. Rates of postoperative complications (duration of pressors, sedative medicaiton and duration of hospital stay, and mechanical ventilation were higher in the group with PH. Of the five (5.4%) infants who died, four received iNO and ECMO. Death or postoperative complications tended to be associated with lower gestational age [OR 0.689; 95% CI: 0.469-1.012, P = 0.058] but not with D-TGA category or bypass duration. CONCLUSIONS: Despite aggressive treatment with iNO and ECMO, the coexistence of PH in this population is associated with higher rates of mortality and postoperative complications. Our results also suggest that an early term birth may be associated with PH in infants with D-TGA. PMID- 26554403 TI - AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting. AB - The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. PMID- 26554401 TI - The sequence of sequencers: The history of sequencing DNA. AB - Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and technologies to facilitate this feat, sequencing DNA and RNA molecules. This time-scale has witnessed tremendous changes, moving from sequencing short oligonucleotides to millions of bases, from struggling towards the deduction of the coding sequence of a single gene to rapid and widely available whole genome sequencing. This article traverses those years, iterating through the different generations of sequencing technology, highlighting some of the key discoveries, researchers, and sequences along the way. PMID- 26554406 TI - Natural Procreative Technology for Treating Infertility. PMID- 26554404 TI - The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. AB - Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance. To overcome this clinical obstacle, our goal was to identify inhibitors with improved potency that can target intractable ALK variants such as F1174L. We find that PF-06463922 has high potency across ALK variants and inhibits ALK more effectively than crizotinib in vitro. Most importantly, PF-06463922 induces complete tumor regression in both crizotinib-resistant and crizotinib-sensitive xenograft mouse models of neuroblastoma, as well as in patient-derived xenografts harboring the crizotinib resistant F1174L or F1245C mutations. These studies demonstrate that PF-06463922 has the potential to overcome crizotinib resistance and exerts unprecedented activity as a single targeted agent against F1174L and F1245C ALK-mutated xenograft tumors, while also inducing responses in an R1275Q xenograft model. Taken together, these results provide the rationale to move PF-06463922 into clinical trials for treatment of patients with ALK-mutated neuroblastoma. SIGNIFICANCE: The next-generation ALK/ROS1 inhibitor PF-06463922 exerts unparalleled activity in ALK-driven neuroblastoma models with primary crizotinib resistance. Our biochemical and in vivo data provide the preclinical rationale for fast-tracking the development of this agent in children with relapsed/refractory ALK-mutant neuroblastoma. PMID- 26554407 TI - Prostate Cancer Screening: The Pendulum has Swung, and the Burden of Proof Is with Proponents. PMID- 26554408 TI - Prostate Cancer Screening. AB - Among American men, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death. Although prostate-specific antigen (PSA) testing has been used to screen for prostate cancer for more than 25 years, the test has low sensitivity and specificity, and there is no clear evidence for determining what threshold warrants prostate biopsy. Only one of five randomized controlled trials of PSA screening showed an effect on prostate cancer-specific mortality, and the absolute reduction in deaths from prostate cancer was one per 781 men screened after 13 years of follow-up. None of the trials showed benefit in all-cause mortality, and screening increased prostate cancer diagnoses by about 60%. Harms of screening include adverse effects from prostate biopsy, overdiagnosis and overtreatment, and anxiety. One-half of screen-detected prostate cancers will not cause symptoms in the patient's lifetime, and 80% to 85% of men who choose observation will not die from prostate cancer within 15 years. Adverse effects of radical prostatectomy include perioperative complications, erectile dysfunction, and urinary incontinence. Radiation therapy can cause acute toxicity leading to urinary urgency, dysuria, diarrhea, and rectal pain; late toxicity includes erectile dysfunction, rectal bleeding, and urethral stricture. Despite variations across guidelines, no organization recommends routine PSA testing, and all endorse some form of shared decision making before testing. If screening is performed, it should generally be discontinued at 70 years of age. PMID- 26554409 TI - Corticosteroid Injections for Common Musculoskeletal Conditions. AB - Family physicians considering corticosteroid injections as part of a comprehensive treatment plan for musculoskeletal diagnoses will find few high quality studies to assist with evidence-based decision making. Most studies of corticosteroid injections for the treatment of osteoarthritis, tendinopathy, bursitis, or neuropathy include only small numbers of patients and have inconsistent long-term follow-up. Corticosteroid injections for the treatment of adhesive capsulitis result in short-term improvements in pain and range of motion. For subacromial impingement syndrome, corticosteroid injections provide short-term pain relief and improvement in function. In medial and lateral epicondylitis, corticosteroid injections offer only short-term improvement of symptoms and have a high rate of symptom recurrence. Corticosteroid injections for carpal tunnel syndrome may help patients avoid or delay surgery. Trigger finger and de Quervain tenosynovitis may be treated effectively with corticosteroid injections. Patients with hip or knee osteoarthritis may have short-term symptom relief with corticosteroid injections. PMID- 26554410 TI - Diagnosis and Treatment of Gastroesophageal Reflux in Infants and Children. AB - Gastroesophageal reflux is defined as the passage of stomach contents into the esophagus with or without accompanied regurgitation (spitting up) and vomiting. It is a normal physiologic process that occurs throughout the day in infants and less often in children and adolescents. Gastroesophageal reflux disease (GERD) is reflux that causes troublesome symptoms or leads to medical complications. The diagnoses of gastroesophageal reflux and GERD are based on the history and physical examination. Diagnostic tests, such as endoscopy, barium study, multiple intraluminal impedance, and pH monitoring, are reserved for when there are atypical symptoms, warning signs, doubts about the diagnosis, or suspected complications or treatment failure. In infants, most regurgitation resolves by 12 months of age and does not require treatment. Reflux in infants may be treated with body position changes while awake, lower-volume feedings, thickening agents (i.e., rice cereal), antiregurgitant formula, extensively hydrolyzed or amino acid formulas, and, in breastfed infants, eliminating cow's milk and eggs from the mother's diet. Lifestyle changes to treat reflux in children and adolescents include sleeping position changes; weight loss; and avoiding smoking, alcohol, and late evening meals. Histamine H2 receptor antagonists and proton pump inhibitors are the principal medical therapies for GERD. They are effective in infants, based on low-quality evidence, and in children and adolescents, based on low- to moderate-quality evidence. Surgical treatment is available, but should be considered only when medical therapy is unsuccessful or is not tolerated. PMID- 26554411 TI - Reducing Amputation Rates After Severe Frostbite. PMID- 26554412 TI - Screening for Thyroid Dysfunction. PMID- 26554413 TI - Unilateral Shoulder Weakness and Visual Deformity in a Young Military Recruit. PMID- 26554414 TI - Levomilnacipran (Fetzima) for Major Depressive Disorder. PMID- 26554416 TI - Gastroesophageal Reflux in Infants and Children. PMID- 26554418 TI - Modification of Silicone Elastomer Surfaces with Zwitterionic Polymers: Short Term Fouling Resistance and Triggered Biofouling Release. AB - We present a method for dual-mode-management of biofouling by modifying surface of silicone elastomers with zwitterionic polymeric grafts. Poly(sulfobetaine methacrylate) was grafted from poly(vinylmethylsiloxane) elastomer substrates using thiol-ene click chemistry and surface-initiated, controlled radical polymerization. These surfaces exhibited both fouling resistance and triggered fouling-release functionality. The zwitterionic polymers exhibited fouling resistance over short-term (~hours) exposure to bacteria and barnacle cyprids. The biofilms that eventually accumulated over prolonged-exposure (~days) were easily detached by applying mechanical strain to the elastomer substrate. Such dual-functional surfaces may be useful in developing environmentally and biologically friendly coatings for biofouling management on marine, industrial, and biomedical equipment because they can obviate the use of toxic compounds. PMID- 26554417 TI - p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells. AB - Estrogen receptor alpha (ERalpha) is highly expressed in most breast cancers. Consequently, ERalpha modulators, such as tamoxifen, are successful in breast cancer treatment, although tamoxifen resistance is commonly observed. While tamoxifen resistance may be caused by altered ERalpha signaling, the molecular mechanisms regulating ERalpha signaling and tamoxifen resistance are not entirely clear. Here, we found that PAK4 expression was consistently correlated to poor patient outcome in endocrine treated and tamoxifen-only treated breast cancer patients. Importantly, while PAK4 overexpression promoted tamoxifen resistance in MCF-7 human breast cancer cells, pharmacological treatment with a group II PAK (PAK4, 5, 6) inhibitor, GNE-2861, sensitized tamoxifen resistant MCF-7/LCC2 breast cancer cells to tamoxifen. Mechanistically, we identified a regulatory positive feedback loop, where ERalpha bound to the PAK4 gene, thereby promoting PAK4 expression, while PAK4 in turn stabilized the ERalpha protein, activated ERalpha transcriptional activity and ERalpha target gene expression. Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha-dependent transcription. In conclusion, PAK4 may be a suitable target for perturbing ERalpha signaling and tamoxifen resistance in breast cancer patients. PMID- 26554419 TI - NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research. AB - BACKGROUND: A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. OBJECTIVE: This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. METHODS: NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result of the encryption, concatenated with the random number r, is the final NHash study identifier. RESULTS: We performed experiments using a large synthesized dataset comparing NHash with random strings, and demonstrated neglegible probability for collision. We implemented NHash for the Center for SUDEP Research (CSR), a National Institute for Neurological Disorders and Stroke-funded Center Without Walls for Collaborative Research in the Epilepsies. This multicenter collaboration involves 14 institutions across the United States and Europe, bringing together extensive and diverse expertise to understand sudden unexpected death in epilepsy patients (SUDEP). CONCLUSIONS: The CSR Data Repository has successfully used NHash to link deidentified multimodal clinical data collected in participating CSR institutions, meeting all desired objectives of NHash. PMID- 26554420 TI - The Treatment of Non-Traumatic Meniscus Lesions. AB - BACKGROUND: Most meniscus lesions are of non-traumatic origin. The indications for partial meniscectomy are controversial. METHODS: We systematically searched the literature for randomized controlled trials (RCTs) comparing partial meniscectomy with non-surgical treatment. RESULTS: Of 6870 articles retrieved by the literature search, we were able to include six in this systematic review. Five trials showed no difference between the clinical outcomes of patients who underwent arthroscopic partial meniscectomy and those who underwent control treatment (arthroscopic lavage, physiotherapy, glucocorticoids). In three trials, however, symptoms improved in 21-30% of the patients in the physiotherapy group only after they underwent arthroscopic partial meniscectomy (crossover design). In two trials, the percentage of patients who crossed over from one treatment arm to the other was markedly lower; in one, the frequency of crossing over was not reported. In one RCT, the patients who underwent arthroscopic partial meniscectomy had significantly less pain and other symptoms. Five of the six trials had acceptable scores for method, but all had weaknesses. These mainly concerned the description of the surgical techniques and the failure to take account of analgesic use-in particular, the use of non-steroidal antiinflammatory drugs (NSAIDs). CONCLUSION: For most patients with non-traumatic meniscus lesions, surgical and non-surgical treatments seem to be of equal value; only one of the six included trials revealed lower pain and symptom scores after arthroscopic partial meniscectomy. In multiple trials, however, the crossover analysis showed that non-surgical treatment fails for some patients. These patients may benefit from arthroscopic partial meniscectomy. Further trials are needed to better define this subgroup of patients. PMID- 26554421 TI - The Reduction in Antibiotic Use in Hospitals. AB - BACKGROUND: Over 350 000 patients are treated in German hospitals for sepsis or pneumonia each year. The rate of antibiotic use in hospitals is high. The growing problem of drug resistance necessitates a reconsideration of antibiotic treatment strategies. METHODS: Antibiotics were given liberally in the years 2010 and 2011 in a German 312-bed hospital. Special training, standardized algorithms to prevent unnecessary drug orders, and uniform recommendations were used in 2012 and 2013 to lessen antibiotic use. We retrospectively studied the hospital's mortality figures and microbiological findings to analyze how well these measures worked. RESULTS: Antibiotic consumption fell from 67.1 to 51.0 defined daily doses (DDD) per 100 patient days (p <0.001) from the period 2010-2011 to the period 2012-2013. The mortality of patients with a main diagnosis of sepsis fell from 1% (95/305) to 19% (63/327; p = 0.001), while that of patients with a main diagnosis of pneumonia fell from 12% (22/178) to 6% (15/235; p = 0.038). The overall mortality fell from 3.0% (623/ 20 954) to 2.5% (576/22 719; p = 0.005). In patients with nosocomial urinary tract infections with Gram-negative pathogens (not necessarily exhibiting three- or fourfold drug resistance), the rate of resistance to three or four of the antibiotics tested fell from 11% to 5%. CONCLUSION: Reducing in-hospital antibiotic use is an achievable goal and was associated in this study with lower mortality and less drug resistance. The findings of this single-center, retrospective study encourage a more limited and focused approach to the administration of antibiotics. PMID- 26554422 TI - Extent of Lateral Neck Dissection in Differentiated Thyroid Carcinoma. PMID- 26554423 TI - In Reply. PMID- 26554424 TI - Influence of Coherent Tunneling and Incoherent Hopping on the Charge Transfer Mechanism in Linear Donor-Bridge-Acceptor Systems. AB - The mechanism of charge transfer has been observed to change from tunneling to hopping with increasing numbers of DNA base pairs in polynucleotides and with the length of molecular wires. The aim of this paper is to investigate this transition by examining the population dynamics using a tight-binding Hamiltonian with model parameters to describe a linear donor-bridge-acceptor (D-B-A) system. The model includes a primary vibration and an electron-vibration coupling at each site. A further coupling of the primary vibration with a secondary phonon bath allows the system to dissipate energy to the environment and reach a steady state. We apply the quantum master equation (QME) approach, based on second-order perturbation theory in a quantum dissipative system, to examine the dynamical processes involved in charge-transfer and follow the population transfer rate at the acceptor, ka, to shed light on the transition from tunneling to hopping. With a small tunneling parameter, V, the on-site population tends to localize and form polarons, and the hopping mechanism dominates the transfer process. With increasing V, the population tends to be delocalized and the tunneling mechanism dominates. The competition between incoherent hopping and coherent tunneling governs the mechanism of charge transfer. By varying V and the total number of sites, we also examine the onset of the transition from tunneling to hopping with increasing length. PMID- 26554425 TI - Determining the Time Window for Dynamic Nanowire Cell Penetration Processes. AB - Nanowire (NW) arrays offer opportunities for parallel, nondestructive intracellular access for biomolecule delivery, intracellular recording, and sensing. Spontaneous cell membrane penetration by vertical nanowires is essential for these applications, yet the time- and geometry-dependent penetration process is still poorly understood. In this work, the dynamic NW-cell interface during cell spreading was examined through experimental cell penetration measurements combined with two mechanical models based on substrate adhesion force or cell traction forces. Penetration was determined by comparing the induced tension at a series of given membrane configurations to the critical membrane failure tension. The adhesion model predicts that penetration occurs within a finite window shortly after initial cell contact and adhesion, while the traction model predicts increasing penetration over a longer period. NW penetration rates determined from a cobalt ion delivery assay are compared to the predicted results from the two models. In addition, the effects of NW geometry and cell properties are systematically evaluated to identify the key factors for penetration. PMID- 26554426 TI - Selenium Partitioning and Removal Across a Wet FGD Scrubber at a Coal-Fired Power Plant. AB - Selenium has unique fate and transport through a coal-fired power plant because of high vapor pressures of oxide (SeO2) in flue gas. This study was done at full scale on a 900 MW coal-fired power plant with electrostatic precipitator (ESP) and wet flue gas desulfurization (FGD) scrubber. The first objective was to quantify the partitioning of selenium between gas and condensed phases at the scrubber inlet and outlet. The second objective was to determine the effect of scrubber operation conditions (pH, mass transfer, SO2 removal) on Se removal in both particulate and vapor phases. During part of the testing, hydrated lime (calcium hydroxide) was injected upstream of the scrubber. Gas-phase selenium and particulate-bound selenium were measured as a function of particle size at the inlet and outlet of the scrubber. The total (both phases) removal of Se across the scrubber averaged 61%, and was enhanced when hydrated lime sorbent was injected. There was evidence of gas-to-particle conversion of selenium across the scrubber, based on the dependence of selenium concentration on particle diameter downstream of the scrubber and on thermodynamic calculations. PMID- 26554427 TI - Identifying opportunities in EHR to improve the quality of antibiotic allergy data. AB - BACKGROUND: Antimicrobial resistance is a growing, global public health crisis, due in large part to the overuse and misuse of antibiotics. Understanding medication allergy data and allergy reactions that are documented in electronic health records (EHRs) can help to identify opportunities to improve the quality of documentation of beta-lactam allergies, thus potentially reducing the prescribing of alternative antibiotics. METHODS: Medication allergies and allergy reactions recorded in the EHR for 319 051 patients seen across 32 community health centers were reviewed. Patients with a beta-lactam allergy recorded in their EHR were identified. Free text, as well as standardized allergy and allergy reaction fields, were analyzed. RESULTS: Among patients, 9.1% (n = 29 095) had evidence of a beta-lactam allergy recorded in their EHR. Women, white, and non Hispanic patients were more likely to have a documented allergy compared to men, black, and Hispanic patients. Among all patients with a documented beta-lactam allergy, 36.2% had an empty or missing allergy reaction description in their EHR. CONCLUSIONS: Findings suggest that current EHR documentation practices among the health centers reviewed do not provide enough information on allergic reactions to allow providers to discern between true allergies and common, but anticipated, drug side effects. Improved EHR documentation guidance, training that reinforces the use of standardized data and more detailed recording of allergic reactions, combined with initiatives to address patient barriers including health literacy, may help to improve the accuracy of drug allergies in patients' records. These initiatives, combined with antimicrobial stewardship programs, can help to reduce inappropriate prescribing of alternative antibiotics when beta-lactam antibiotics are first-line and can be tolerated. PMID- 26554428 TI - VERTIcal Grid lOgistic regression (VERTIGO). AB - OBJECTIVE: To develop an accurate logistic regression (LR) algorithm to support federated data analysis of vertically partitioned distributed data sets. MATERIAL AND METHODS: We propose a novel technique that solves the binary LR problem by dual optimization to obtain a global solution for vertically partitioned data. We evaluated this new method, VERTIcal Grid lOgistic regression (VERTIGO), in artificial and real-world medical classification problems in terms of the area under the receiver operating characteristic curve, calibration, and computational complexity. We assumed that the institutions could "align" patient records (through patient identifiers or hashed "privacy-protecting" identifiers), and also that they both had access to the values for the dependent variable in the LR model (eg, that if the model predicts death, both institutions would have the same information about death). RESULTS: The solution derived by VERTIGO has the same estimated parameters as the solution derived by applying classical LR. The same is true for discrimination and calibration over both simulated and real data sets. In addition, the computational cost of VERTIGO is not prohibitive in practice. DISCUSSION: There is a technical challenge in scaling up federated LR for vertically partitioned data. When the number of patients m is large, our algorithm has to invert a large Hessian matrix. This is an expensive operation of time complexity O(m(3)) that may require large amounts of memory for storage and exchange of information. The algorithm may also not work well when the number of observations in each class is highly imbalanced. CONCLUSION: The proposed VERTIGO algorithm can generate accurate global models to support federated data analysis of vertically partitioned data. PMID- 26554429 TI - Dispatch from the non-HITECH-incented Health IT world: electronic medication history adoption and utilization. AB - OBJECTIVE: To document national trends of electronic medication history use in the ambulatory setting and describe the characteristics and predicting factors of providers who regularly use medication history transaction capabilities through their e-prescribing systems. MATERIALS AND METHODS: The study used provider initiated medication history data requests, electronically sent over an e prescribing network from all 50 states and the District of Columbia. Data from 138,000 prescribers were evaluated using multivariate analyses from 2007 to 2013. RESULTS: Medication history use showed significant growth, increasing from 8 to 850 million history requests during the study period. Prescribers on the network for <5 years had a lower likelihood of requests than those on the network for 5 or more years. Although descriptive analyses showed that prescribers in rural areas were alongside e-prescribing, and requesting medication histories more often than those in large and small cities, these findings were not significant in multivariate analyses. Providers in orthopedic surgery and internal medicine had a higher likelihood of more requests than family practice prescribers, with 12% and 7% higher likelihood, respectively. DISCUSSION: Early adopters of e prescribing have remained medication history users and have continually increased their volume of requests for medication histories. CONCLUSION: Despite the fact that the use of medication histories through e-prescribing networks in the ambulatory care setting has not been encouraged through federal incentive programs, there has been substantial growth in the use of medication histories offered through e-prescribing networks. PMID- 26554430 TI - Rapid High-pH Reverse Phase StageTip for Sensitive Small-Scale Membrane Proteomic Profiling. AB - Membrane proteins are crucial targets for cancer biomarker discovery and drug development. However, in addition to the inherent challenges of hydrophobicity and low abundance, complete membrane proteome coverage of clinical specimen is usually hindered by the requirement of large amount of starting materials. Toward comprehensive membrane proteomic profiling for small amounts of samples (10 MUg), we developed high-pH reverse phase (Hp-RP) combined with stop-and-go extraction tip (StageTip) technique, as a fast (~15 min.), sensitive, reproducible, high resolution and multiplexed fractionation method suitable for accurate quantification of the membrane proteome. This approach provided almost 2-fold enhanced detection of peptides encompassing transmembrane helix (TMH) domain, as compared with strong anion exchange (SAX) and strong cation exchange (SCX) StageTip techniques. Almost 5000 proteins (~60% membrane proteins) can be identified in only 10 MUg of membrane protein digests, showing the superior sensitivity of the Hp-RP StageTip approach. The method allowed up to 9- and 6 fold increase in the identification of unique hydrophobic and hydrophilic peptides, respectively. The Hp-RP StageTip method enabled in-depth membrane proteome profiling of 11 lung cancer cell lines harboring different EGFR mutation status, which resulted in the identification of 3983 annotated membrane proteins. This provides the largest collection of reference peptide spectral data for lung cancer membrane subproteome. Finally, relative quantification of membrane proteins between Gefitinib-resistant and -sensitive lung cancer cell lines revealed several up-regulated membrane proteins with key roles in lung cancer progression. PMID- 26554431 TI - Iron-Catalyzed Synthesis of C2 Aryl- and N-Heteroaryl-Substituted Tetrahydropyrans. AB - An iron-catalyzed cyclization of hydroxy allylic derivatives into tetrahydropyrans possessing an N-heteroaryl at C2 is disclosed. The reaction proceeds with good yield and in high diastereoselectivity in favor of the more stable isomer. The diastereoselectivity results from an iron-induced reopening of the tetrahydropyrans, allowing a thermodynamic equilibration. The method allows access to a variety of 2,6-disubstituted as well as 2,4,6-trisubstituted tetrahydropyrans that could be considered as attractive scaffolds for the pharmaceutical industry. PMID- 26554432 TI - Evaluation of a strapless heart rate monitor during simulated flight tasks. AB - Pilots are under high task demands during flight. Monitoring pilot's physiological status is very important in the evaluation of pilot's workload and flight safety. Recently, physiological status monitor (PSM) has been embedded into a watch that can be used without a conventional chest strap. This makes it possible to unobtrusively monitor, log and transmit pilot's physiological measurements such as heart rate (HR) during flight tasks. The purpose of this study is to validate HR recorded by a strapless heart rate watch against criterion ECG-derived HR. Ten commercial pilots (mean +/- SD : age: 39.1 +/- 7.8 years; total flight hours 7173.2 +/- 5270.9 hr) performed three routinely trained flight tasks in a full flight simulator: wind shear go-around (WG), takeoff and climb (TC), and hydraulic failure (HF). For all tasks combined (overall) and for each task, differences between the heart rate watch measurements and the criterion data were small (mean difference [95% CI]: overall: -0.71 beats/min [ 0.85, -0.57]; WG: -0.90 beats/min [-1.15, -0.65]; TC: -0.69 beats/min [-0.98, 0.40]; HF: -0.61 beats/min [-0.80, -0.42]). There were high correlations between the heart rate watch measurements and the ECG-derived HR for all tasks (r >= 0.97, SEE < 3). Bland-Altman plots also show high agreements between the watch measurements and the criterion HR. These results suggest that the strapless heart rate watch provides valid measurements of HR during simulated flight tasks and could be a useful tool for pilot workload evaluation. PMID- 26554433 TI - New Q lineage found in bovine (Bos taurus) of Iberian Peninsula. AB - The northern Iberian Peninsula is home to a variety of autochthonous cattle breeds, such as the Terrena and Pirenaica. With the objective of characterizing the matrilineal lineages of these breeds, a study of mitochondrial DNA was performed. The D-loop of 155 individuals was analyzed and most of the individuals were carriers of the T3 haplogroup, while haplogroups T and T1 were much less frequent. A Pirenaica individual belonging to the Q haplogroup was found. To verify the presence of the Q haplogroup individual, the entire mitochondrial DNA was sequenced and compared with two descendants. The individuals were assigned to the Q1 sub-haplogroup. These findings extend the geographic distribution of the Q haplogroup to the south west of the European continent. This new Q1 lineage has seven polymorphisms in the coding region, so this lineage is probably as old as the Q lineages described to date. PMID- 26554434 TI - Approaches to the Surveillance of Foodborne Disease: A Review of the Evidence. AB - Foodborne disease surveillance aims to reduce the burden of illness due to contaminated food. There are several different types of surveillance systems, including event-based surveillance, indicator-based surveillance, and integrated food chain surveillance. These approaches are not mutually exclusive, have overlapping data sources, require distinct capacities and resources, and can be considered a hierarchy, with each level being more complex and resulting in a greater ability to detect and control foodborne disease. Event-based surveillance is generally the least resource-intensive system and makes use of informal data sources. Indicator-based surveillance is seen as traditional notifiable disease surveillance and consists of routinely collected data. Integrated food chain surveillance is viewed as the optimal practice for conducting continuous risk analysis for foodborne diseases, but also requires significant ongoing resources and greater multisectoral collaboration compared to the other systems. Each country must determine the most appropriate structure for their surveillance system for foodborne diseases based on their available resources. This review explores the evidence on the principles, minimum capabilities, and minimum requirements of each type of surveillance and discusses examples from a range of countries. This review forms the evidence base for the Strengthening the Surveillance and Response for Foodborne Diseases: A Practical Manual. PMID- 26554435 TI - Cleaved Slit directs embryonic muscles. AB - The formation of functional musculoskeletal system relies on proper connectivity between muscles and their corresponding tendon cells. In Drosophila, larval muscles are born during early embryonic stages, and elongate toward tendons that are embedded within the ectoderm in later. The Slit/Robo signaling pathway had been implicated in the process of muscle elongation toward tendons. Here we discuss our recent findings regarding the critical contribution of Slit cleavage for immobilization and stabilization of the Slit signal on the tendon cells. Slit cleavage produces 2 polypeptides, the N-terminal Slit-N, which is extremely stable, undergoes oligomerization, and associates with the tendon cell surfaces, and the C-terminal Slit-C, which rapidly degrades. Slit cleavage leads to immobilization of Slit signaling on tendons, leading to a short-range repulsion, which eventually arrest further muscle elongation. Robo2, which is co-expressed with Slit by the tendon cells facilitates Slit cleavage. This activity does not require the cytoplasmic signaling domain of Robo2. We suggest that Robo2 dependent Slit cleavage, and the formation of Slit-N oligomers on the tendon cell surfaces direct muscle elongation, and provide a stop signal for the approaching muscle, through binding to Robo and Robo3 receptors expressed by the muscles. PMID- 26554436 TI - Association of endothelial microparticle with NO, eNOS, ET-1, and fractional flow reserve in patients with coronary intermediate lesions. AB - Endothelial microparticle (EMP) is a biomarker for endothelial dysfunction. The aim of this study is to investigate the utility of EMP in evaluating coronary intermediate lesions. Participants included 49 patients with coronary intermediate lesions and 24 subjects with normal coronary arteries. Among these subjects, 28 patients accepted fractional flow reserve (FFR). Results showed that level of EMP was significantly higher in the intermediate lesion group. No correlation was found between EMP and FFR value, suggesting that circulating EMP is a systemic marker rather than a focal one. PMID- 26554438 TI - A method to produce fully characterized ubiquitin covalently modified by 4 hydroxy-nonenal, glyoxal, methylglyoxal, and malondialdehyde. AB - Reactive carbonyl species (RCS) and the corresponding protein adducts (advanced glycoxidation or lipoxidation end products, i.e. AGEs and ALEs) are now widely studied from different points of view, since they can be considered as biomarkers, pathogenic factors, toxic mediators and drug targets. One of the main limits of the research in this field is the lack of standardized and fully characterized AGEs and ALEs to be used for biological, toxicological, and analytical studies. In this work, we set up a procedure to prepare and fully characterize a set of AGEs and ALEs by incubating ubiquitin - a model protein selected as target for carbonylation - with four different RCS: 4-hydroxy-trans-2 nonenal (HNE), methylglyoxal (MGO), glyoxal (GO), and malondialdehyde (MDA). After 24 h of incubation, the extent of protein carbonylation was estimated using a recently developed quantitative strategy based on high-resolution mass spectrometry. The resulting AGEs and ALEs were fully characterized by both intact protein and bottom-up analyses in terms of: stoichiometry of the total amount of modified protein, elucidation of the structure of the RCS-deriving adducts, and localization of the RCS-modified amino acids. Each RCS exhibited different reactivity toward ubiquitin, as detected by quantifying the extent of protein modification. The order of reactivity was MGO > GO > HNE > MDA. A variety of reaction products was identified and mapped on lysine, arginine, and histidine residues of the protein. In summary, a highly standardized and reproducible method to prepare fully characterized AGEs/ALEs is here presented. PMID- 26554439 TI - Restless-legs syndrome and insomnia in hemodialysis patients. AB - AIM/BACKGROUND: Restless legs syndrome (RLS) is a common neurological movement disorder which is commonly seen in hemodialysis (HD) patients. Insomnia, depression, and anxiety disorders frequently show concurrence. In this study, we aimed to investigate RLS and insomnia prevalence and related factors in HD patients. SUBJECTS AND METHODS: Patients who were under HD treatment and healthy controls with similar mean age, sex ratio, and hypertension and diabetes mellitus frequency were included in this study. Depression, insomnia, and daytime sleepiness assessments were performed by using Beck Depression Inventory, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of RLS was made using the International RLS Study Group consensus criteria. RESULTS: About 156 HD patients and 35 controls were enrolled. The mean age was 50.6 in the HD group and 49.7 in the control group. Female sex was 43.9% in the HD group and 57.1% in the control group. RLS was significantly more frequent in HD patients compared with controls. The rate of sub-threshold insomnia and insomnia with moderate severity was higher in HD patients. While insomnia severity score and diabetes mellitus were significantly associated with the presence of RLS, depression, RLS, older age, and being under HD treatment were independently associated with insomnia severity. CONCLUSIONS: HD patients commonly have RLS and insomnia. Insomnia and diabetes mellitus seem to be major factors underlying RLS in HD patients. Furthermore, depression and RLS seem to be closely related to insomnia in these patients. Treatment of depression, insomnia, and RLS may be beneficial to improve quality of life in HD patients. PMID- 26554440 TI - AMPD1 polymorphism and response to regadenoson. AB - AIMS: AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. SUBJECTS & METHODS: Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. RESULTS: Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 +/- 25 vs 5 +/ 13%; p = 0.01) ([%] SBP change to nadir: -3 +/- 15 vs -7 +/- 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). CONCLUSION: AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects. PMID- 26554441 TI - Hybrid and open surgery of Trans-Atlantic Inter-Society II type C and D iliac occlusive disease and concomitant lesion of common femoral artery. AB - BACKGROUND: The purpose of our study was to compare immediate and long-term results of hybrid repair and open aortofemoral reconstructions in the patients with lower extremity peripheral arterial disease of Trans-Atlantic Inter-Society (TASC) II Type C and Type D iliac lesions in combination with the concomitant lesion of common femoral artery (CFA). METHODS: We have included in this prospective case-controlled study 112 patients with extensive iliac and CFA occlusive disease. The study was conducted from 2009 till 2014. In the first group there were 46 patients who received recanalization and stenting of iliac arteries in combination with endarterectomy and angioplasty of common femoral and deep femoral arteries. In the second group there were 66 patients who received aortofemoral bypass. All patients had chronic ischemia (Stage 3-5, Rutherford classification) for TransAtlantic Inter-Society (TASC II) type C and D iliac occlusive disease. RESULTS: We have not found any significant differences in demographic details between the groups. At the same time there were significant differences in clinical data (coronary heart disease and stage of chronic ischemia) between the groups. Early (<30 days) thrombosis of the stented iliac segment or aorto-femoral bypass was detected in three patients (6.5%) in the first group and three cases (4.5%) in the second group. Thrombectomies using a Fogarty catheter were successful performed in both groups. The average length of the follow-up was 3.1 years (in the range of 6 to 48 months), with a mean follow up of 3.3 years for the open repair (range 6-48 months) and 2.8 years for the hybrid repair (range 6-48 months) group. At the end of the follow-up period, thrombosis of the stented iliac segment or aortofemoral bypass was detected in 5 (10.9%) patients of the 1st group and 5 (7.8%) patients of the 2nd group. The cumulative primary patency rates at 12, 24 and 36 months were 95.7%, 90.8%, 84.3% in the 1st group and 98.5%, 95.4%, 90.4% in the 2nd group, respectively (P=0.84). The limb salvage rates in our study at 12 and 24 months were 97.8% and 93.8% in the 1st group and 100% and 98% in the 2nd group, respectively (P=0.23). CONCLUSIONS: Hybrid surgery including recanalization and stenting of iliac artery in combination with endarterectomy and angioplasty of common femoral and deep femoral arteries is an effective (at least in the mid-term period) minimally invasive treatment for patients with multifocal peripheral artery disease. This single-center study supports the safety and durable efficacy of hybrid procedures in a limited cohort of patients, thus emphasizing the need for larger scale clinical trials to evaluate this approach against aortofemoral bypass. PMID- 26554442 TI - Endovascular aneurysm repair with fascia suture technique: short and mid-term results. AB - BACKGROUND: Percutaneous endovascular aneurysm repair (p-EVAR), has been widely spread based on the recent improvements in stent-graft technology and mainly in delivery system downsizing. Aim of this study is to investigate the safety and efficacy of fascia suture technique (FST) in p-EVAR during the short and mid-term follow-up (FU). METHODS: Between April 2011 and July 2013, 64 consecutive patients with abdominal aortic aneurysm were enrolled in a prospective single center registry. Fifty-four patients were eligible for elective p-EVAR assisted by the fascia suture technique. Patients were prospectively followed with duplex scan 24 hours and 30 days postoperatively and with CTA annually thereafter. Femoral haematoma, pseudoaneurysm and limb ischaemia were the primary outcomes. RESULTS: The study investigated 103 femoral arteries reconstructions using the FST. Intraoperatively, one patient was diagnosed with limb ischaemia treated with open repair. During the short-term, 4 (3.8%) pseudoaneurysms were diagnosed, treated with open (2) or endovascular (2) repair. During mid-term 43 patients (85 arteries, 82.6%) underwent CTA. Eighteen (17.4%) patients were lost at FU. At 12 months CTA two pseudoaneurysms (2.35%) were detected, treated with open repair. CONCLUSIONS: The FST seems safe and effective for femoral reconstruction after p EVAR. Complications are comparable to closure devices and to conventional repair. PMID- 26554444 TI - Passing the Baton. PMID- 26554445 TI - Basal Cell Carcinoma is as Common as the Sum of all Other Cancers: Implications for Treatment Capacity. AB - Reliable estimates of disease incidence are fundamental to planning future healthcare services. However, in many countries registration of basal cell carcinoma (BCC) is often non-existent. This study examines how many BCC treatments were carried out in Denmark in 2013. The Danish Cancer Registry and the Danish Pathology Registry were used to examine how many BCC treatments were registered, and a test sample was taken from Bispebjerg Hospital to examine the number treated but not registered. The study showed that 21.7% of BCC treatments were performed solely on a clinical diagnosis. Furthermore, some records are inadequate in relation to BCC registration, as BCCs treated are 3 times the number of individuals in the Danish Cancer Registry, and there are nearly as many BCCs as the sum of all other cancers. The increasing BCC incidence will result in difficulties in ensuring treatment capacity. PMID- 26554443 TI - Misfolding Ectodomain Mutations of the Lutropin Receptor Increase Efficacy of Hormone Stimulation. AB - We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention. However, we made the unusual discovery that the intrinsic efficacy for agonist-stimulated cAMP in the reduced numbers of receptors on the cell surface was greatly increased relative to the same low number of cell surface wild-type receptor. Remarkably, this appears to be a general attribute of misfolding mutations in the ectodomains, but not serpentine domains, of the gonadotropin receptors. These findings suggest that there must be a common, shared mechanism by which disparate mutations in the ectodomain that cause misfolding and therefore reduced cell surface expression concomitantly confer increased agonist efficacy to those receptor mutants on the cell surface. Our data further suggest that, due to their increased agonist efficacy, extremely small changes in cell surface expression of misfolded ectodomain mutants cause larger than expected alterations in the cellular response to agonist. Therefore, for inactivating LHCGR mutations causing ectodomain misfolding, the numbers of cell surface mutant receptors on fetal Leydig cells of 46,XY individuals exert a more exquisite effect on the relative severity of the clinical phenotypes than already appreciated. PMID- 26554446 TI - Isolation and Culture Expansion of Tumor-specific Endothelial Cells. AB - Freshly isolated tumor-specific endothelial cells (TEC) can be used to explore molecular mechanisms of tumor angiogenesis and serve as an in vitro model for developing new angiogenesis inhibitors for cancer. However, long-term in vitro expansion of murine endothelial cells (EC) is challenging due to phenotypic drift in culture (endothelial-to-mesenchymal transition) and contamination with non-EC. This is especially true for TEC which are readily outcompeted by co-purified fibroblasts or tumor cells in culture. Here, a high fidelity isolation method that takes advantage of immunomagnetic enrichment coupled with colony selection and in vitro expansion is described. This approach generates pure EC fractions that are entirely free of contaminating stromal or tumor cells. It is also shown that lineage-traced Cdh5(cre):ZsGreen(l/s/l) reporter mice, used with the protocol described herein, are a valuable tool to verify cell purity as the isolated EC colonies from these mice show durable and brilliant ZsGreen fluorescence in culture. PMID- 26554447 TI - Evaluation of an on-farm method to assess colostrum IgG content in sows. AB - The objective of this work was to investigate the evaluation of swine colostrum immunoglobulin G (IgG) concentration using the Brix refractometer. Colostrum samples were collected across all teats, from 124 sows of mixed parities. According to sampling time, three categories were created: samples available from 9 h before the onset of parturition until the first piglet was born were classified as before farrowing; samples collected after the first birth until 4 h later were classified as during farrowing; and finally samples collected from this point until 14 h after parturition, were classified as after farrowing. Samples were drawn and divided into three portions; one was immediately analyzed, a second was refrigerated and the third was frozen at -20 degrees C. Fresh and refrigerated colostrum samples were analyzed at the farm with a Brix refractometer. IgG content of frozen samples was analyzed using a Brix refractometer, with a subset of 42 samples also tested with a commercially available radial immune diffusion (RID) kit. The Brix percentage ranged from 18.3% to 33.2%. Brix percentage repeatability, assessed by the intraclass correlation coefficient (ICC), was very strong (fresh ICC=0.98, refrigerated ICC=0.88 and frozen ICC=0.99). One-way repeated-measures ANOVA showed that storage temperature did not affect BRIX percentage of colostrum IgG (P>0.05). ANOVA results show a significant effect of sampling time on colostrum immunoglobulin concentration, measured with both Brix and RID (Brix: P<0.003; RID: P<0.05). Immunoglobulin G concentration measured by RID ranged from 13.27 to 35.08 mg/ml. Pearson correlation coefficient revealed that Brix percentage was positively correlated (r=0.56, P<0.001) with RID results (regression equation: RID=1.01 (+/-0.2) Brix -1.94 (+/-5.66); R 2=0.31). The results of this study indicate that the Brix refractometer provides a simple, fast and inexpensive estimation of colostrum IgG in sows. PMID- 26554448 TI - Completeness of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection Reporting From Outpatient Hemodialysis Facilities to the National Healthcare Safety Network, 2013. AB - Reports of bloodstream infections caused by methicillin-resistant Staphylococcus aureus among chronic hemodialysis patients to 2 Centers for Disease Control and Prevention surveillance systems (National Healthcare Safety Network Dialysis Event and Emerging Infections Program) were compared to evaluate completeness of reporting. Many methicillin-resistant S. aureus bloodstream infections identified in hospitals were not reported to National Healthcare Safety Network Dialysis Event. PMID- 26554449 TI - Antibody induced by one-dose varicella vaccine soon became weak in children: evidence from a cross-sectional seroepidemiological survey in Beijing, PRC. AB - BACKGROUND: Numerous post-licensure studies, mostly from field epidemiological evidences such as outbreak surveys, have demonstrated the effectivenesss and insufficiency of one-dose varicella vaccine in outbreak control. Serological evidence of immunization failure is, however, relatively less reported in contrast. A cross-sectional seroepidemiological survey of Beijing residents was performed in 2012 in the People's Republic of China, after the one-dose varicella vaccine had been widely used for several years. METHODS: Multistage stratified random sampling method was designed to recruit 2 144 subjects. The ELISA method was used to test the present blood samples collected and the reserve samples collected in 2008 to assess the trends of anti-VZV seroprevalence in the past 5 years and to determine the risk factors for varicella infection. RESULTS: The age and sex- adjusted overall anti-VZV seropositivity of Beijing residents in 2012 was 84.5%. Two groups' adjusted overall anti-VZV seroprevalence in 2012 showed obvious growth compared with 2008 (<1 yr old: from 6.3% to 16.9%; 1-4 yr old: from 27.6% to 57.2%). Reported one-dose vaccination history was 71.6% (149/208), 80.9% (182/225) and 82.2% (180/219) in the 1-4 yr, 5-9 yr, 10-14 yr age groups, respectively. Of subjects who had received the one-dose vaccine, 36% (216/603) showed negative anti-VZV concentrations (<110 mIU/mL); additionally 15.9% (96/603) of such subjects' anti-VZV concentrations were in the lowest positive concentration group (110-299 mIU/mL). Seropositivity in permanent residents of 1 9 yr old with verified vaccination was merely 61.8%. Various age groups (1-3 yr, 4-6 yr, and 7-9 yr) all showed seropositivity that gradually decreased with increasing of the interval between vaccination and blood sampling. CONCLUSION: Mass varicella vaccination significantly improved the immunity of younger Beijing residents. However, vaccine-induced anti-VZV antibody soon became weak in children with high coverage (approximately 80%) after vaccination for several years which is significantly higher than reported in pre-licensure studies. A government-funded 2-dose immunization program with mandatory vaccination schedule for Beijing residents may need consideration in the near future. PMID- 26554450 TI - Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse. AB - BACKGROUND: Exposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post menopausal women, several researchers have characterized a possible bi directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation. METHODS: Multivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time. RESULT: Abuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure. CONCLUSIONS: Taken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood. PMID- 26554451 TI - Mechanical fibrinogen-depletion supports heparin-free mesenchymal stem cell propagation in human platelet lysate. AB - BACKGROUND: Pooled human platelet lysate (pHPL) is an efficient alternative to xenogenic supplements for ex vivo expansion of mesenchymal stem cells (MSCs) in clinical studies. Currently, porcine heparin is used in pHPL-supplemented medium to prevent clotting due to plasmatic coagulation factors. We therefore searched for an efficient and reproducible medium preparation method that avoids clot formation while omitting animal-derived heparin. METHODS: We established a protocol to deplete fibrinogen by clotting of pHPL in medium, subsequent mechanical hydrogel disruption and removal of the fibrin pellet. After primary culture, bone-marrow and umbilical cord derived MSCs were tested for surface markers by flow cytometry and for trilineage differentiation capacity. Proliferation and clonogenicity were analyzed for three passages. RESULTS: The proposed clotting procedure reduced fibrinogen more than 1000-fold, while a volume recovery of 99.5 % was obtained. All MSC types were propagated in standard and fibrinogen-depleted medium. Flow cytometric phenotype profiles and adipogenic, osteogenic and chondrogenic differentiation potential in vitro were independent of MSC-source or medium type. Enhanced proliferation of MSCs was observed in the absence of fibrinogen but presence of heparin compared to standard medium. Interestingly, this proliferative response to heparin was not detected after an initial contact with fibrinogen during the isolation procedure. CONCLUSIONS: Here, we present an efficient, reproducible and economical method in compliance to good manufacturing practice for the preparation of MSC media avoiding xenogenic components and suitable for clinical studies. PMID- 26554457 TI - Graded Resistance Exercise And Type 2 Diabetes in Older adults (The GREAT2DO study): methods and baseline cohort characteristics of a randomized controlled trial. AB - BACKGROUND: Type 2 diabetes (T2D) is projected to affect 439 million people by 2030. Medical management focuses on controlling blood glucose levels pharmacologically in a disease that is closely related to lifestyle factors such as diet and inactivity. Physical activity guidelines include aerobic exercise at intensities or volumes potentially unreachable for older adults limited by many co-morbidities. We aim to show for the first time the efficacy of a novel exercise modality, power training (high-velocity, high-intensity progressive resistance training or PRT), in older adults with T2D as a means for improving glycemic control and targeting many associated metabolic and physiological outcomes. Eligibility criteria included community-dwelling men and women previously diagnosed with T2D who met the current definition of metabolic syndrome according to the International Diabetes Federation. Participants were randomized to a fully supervised power training intervention or sham exercise control group for 12 months. Intervention group participants performed whole body machine-based power training at 80%1RM, 3 days per week. The control group undertook the same volume of non-progressive, low-intensity training. Participants were assessed at baseline, 6 months and 12 months and followed for a further 5 years, during which time participants were advised to exercise at moderate-high intensity. Glycemic control (HbA1c) and insulin resistance as measured by the homeostatic model assessment 2 (HOMA2-IR) were the primary outcomes of the trial. Outcome assessors were blinded to group assignment and participants were blinded to the investigators' hypothesis regarding the most effective intervention. RESULTS: We recruited 103 participants (48.5 % women, 71.6 +/- 5.6 years). Participants had 5.1 +/- 1.8 chronic diseases, had been diagnosed with T2D for 8 +/- 6 years and had a body mass index (BMI) of 31.6 +/- 4.0 kg/m(2). Fasting glucose and insulin were 7.3 +/- 2.4 mmol/L and 10.6 +/- 6.3 mU/L, respectively. HbA1c was 54 +/- 12 mmol/mol. Eighty-six participants completed the 12-month assessment and follow-up is ongoing. This cohort had a lower-than-expected dropout (n = 14, 14 %) over the 12-month intervention period. CONCLUSIONS: Power training may be a feasible adjunctive therapy for improving glycemic control for the growing epidemic of T2D in older adults. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12606000436572 (24 September 2006). PMID- 26554458 TI - The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical and immunological manifestations. Several spontaneous and inducible animal models mirror common components of human disease, including the bm12 transfer model. Upon transfer of bm12 splenocytes or purified CD4 T cells, C57BL/6 mice rapidly develop large frequencies of T follicular helper cells (Tfh), germinal center (GC) B cells, and plasma cells followed by high levels of circulating anti nuclear antibodies. Since this model utilizes mice on a pure C57BL/6 background, researchers can quickly and easily study disease progression in transgenic or knockout mouse strains in a relatively short period of time. Here we describe protocols for the induction of the model and the quantitation Tfh, GC B cells, and plasma cells by multi-color flow cytometry. Importantly, these protocols can also be used to characterize disease in most mouse models of SLE and identify Tfh, GC B cells, and plasma cells in other disease models. PMID- 26554459 TI - The Impact of Monitoring on the Initiation of Cardiopulmonary Resuscitation in Children: Friend or Foe? AB - BACKGROUND: The immediate initiation and high quality of basic life support (BLS) are pivotal to improving patient outcome after cardiac arrest. Although cardiorespiratory monitoring could shorten the time to recognize the onset of cardiac arrest, little is known about how monitoring and the misinterpretation of monitor readings could impair the initiation of BLS. In this study, we assessed the speed of initiation and quality of BLS in simulated monitored and nonmonitored pediatric cardiac arrest. METHODS: Sixty residents frequently involved in the care of critically ill children were randomly assigned to either the intervention (monitoring) group or the control (nonmonitoring) group. Participants of both groups performed BLS in 1 of 2 clinically identical, unwitnessed simulated cardiac arrest scenarios. Although in 1 scenario cardiorespiratory monitoring (i.e., electrocardiogram) was attached, the other scenario reflected a nonmonitored cardiac arrest. Time to first chest compression was chosen as the primary outcome variable. Adherence to resuscitation guidelines and subjective performance ratings were secondary outcome variables. RESULTS: Participants in the monitoring group initiated chest compressions significantly later than those in the nonmonitoring group (91 +/- 36 vs 71 +/- 26 seconds, hazard ratio, 0.26; 95% confidence interval, 0.14-0.49, P < 0.001). Six members of the monitoring group did not start chest compression within 5 minutes. Furthermore, adherence to the guidelines was better in the nonmonitoring group. Participants who were previously involved in BLS training did not show better performance. CONCLUSIONS: The presence of cardiorespiratory monitoring significantly delayed or even prevented the initiation of chest compressions and impaired the quality of BLS in simulated pediatric cardiac arrest. Based on these data, specific training should be conducted for exposed personnel. PMID- 26554460 TI - The Mechanism of Mitral Regurgitation Influences the Temporal Dynamics of the Vena Contracta Area as Measured with Color Flow Doppler. AB - BACKGROUND: In patients with mitral regurgitation (MR), the effective regurgitant orifice area can be estimated by measuring the vena contracta area (VCA). We hypothesize that the VCA has characteristic temporal dynamics related to the underlying mechanism of functional mitral regurgitation (FMR) versus degenerative mitral valve disease (DMVD). METHODS: VCA measurements obtained by planimetry of the proximal jet from 3D transesophageal echocardiographic (TEE) color flow Doppler data sets were acquired in 42 cardiac surgical patients, including 22 with FMR and 20 with DMVD. Serial VCAs were measured throughout systole for each patient to evaluate variation in the effective regurgitant orifice area. Tercile averages were compared within and between the FMR and DMVD groups using repeated measures analysis of variance. Pairwise tests were Bonferroni-corrected for the number of comparisons. RESULTS: Normalized average VCA values in patients with FMR revealed a biphasic pattern compared with a monophasic pattern in patients with DMVD. Among FMR patients, normalized average VCA values in early (1.10 +/- 0.32 cm2) and late systole (1.11 +/- 0.33 cm2) were similar but were both significantly greater compared with mid-systole (0.79 +/- 0.22 cm; P = 0.0144 and P = 0.0106, respectively). Among DMVD patients, normalized average VCA values in mid-systole (1.37 +/- 0.15 cm2) were significantly greater than those in early (0.53 +/- 0.14 cm2) and late systole (1.09 +/- 0.18 cm2; P < 0.0001 for both). An analysis of normalized average VCAs also revealed significant differences between the FMR and the DMVD groups during early (1.10 +/- 0.32 cm vs 0.53 +/- 0.14 cm2) and mid-systole (0.79 +/- 0.22 cm2 vs 1.37 +/- 0.15 cm2; P < 0.0001 for both). CONCLUSIONS: VCA dynamics are governed by the mechanism of MR and are observed in FMR patients primarily as a biphasic temporal pattern compared with a monophasic temporal pattern in patients with DMVD. PMID- 26554461 TI - Use of Tranexamic Acid Is Associated with Reduced Blood Product Transfusion in Complex Skull Base Neurosurgical Procedures: A Retrospective Cohort Study. AB - BACKGROUND: Compared with other procedures, complex skull base neurosurgery has the potential for increased intraoperative blood loss yet coagulation near eloquent cranial structures should be minimized. The safety and efficacy of the antifibrinolytic, tranexamic acid in elective neurosurgical procedures is not known. Our primary objective was to determine the relationship between the use of tranexamic acid and transfusion at our institution. Our secondary objective was to determine the incidence of adverse events associated with the use of tranexamic acid. METHODS: In this retrospective cohort study, we included all patients who underwent complex skull base neurosurgical procedures at our institution between 2001 and 2013. Tranexamic acid was introduced during these procedures in 2006. Patient and surgical variables, transfusion data, and adverse events in the perioperative period were abstracted from the medical record. The rates of transfusion and adverse events were compared between patients who did and did not receive tranexamic acid. Multivariate regression was used to identify independent predictors of perioperative transfusion. RESULTS: We compared 245 patients who received tranexamic acid with 274 patients who did not receive the drug during the study period. The 2 groups were similar, with the exception that patients who received tranexamic acid had larger tumors (mean, 3.5 vs 2.9 cm; P < 0.001) and longer procedures (mean, 7.2 vs 6.2 hours, P < 0.001). The rate of perioperative transfusion in patients who received tranexamic acid was lower (7% vs 13%, P = 0.04). After adjusting for preoperative hemoglobin, tumor diameter, and surgical procedure category, the use of tranexamic acid was independently predictive of perioperative transfusion (adjusted odds ratio, 0.32; 95% confidence interval, 0.15-0.65, P = 0.002). The rates of thromboembolic events and seizure were similar between the 2 groups. CONCLUSIONS: Our results demonstrate that tranexamic acid use is associated with reduced transfusion rates in our study population, with no apparent increase in seizure or thrombotic complications. Our data support the need for further randomized clinical trials to evaluate the efficacy and safety of tranexamic acid on perioperative blood loss during complex skull base neurosurgery. PMID- 26554462 TI - Prevalence of Malignant Hyperthermia Diagnosis in New York State Ambulatory Surgery Center Discharge Records 2002 to 2011. AB - BACKGROUND: Malignant hyperthermia (MH) is a rare yet potentially fatal pharmacogenetic disorder triggered by exposure to inhaled anesthetics and the depolarizing neuromuscular blocking drug succinylcholine. Epidemiologic research on MH is largely limited to inpatients. In this study, we examined the prevalence of recorded MH diagnosis in patients discharged from ambulatory surgery centers (ASCs). METHODS: We analyzed the New York State Ambulatory Surgery Dataset for the years 2002 to 2011 and identified patients with a discharge diagnosis of MH due to anesthesia by using the International Classification of Disease, Ninth Revision, Clinical Modification code 995.86. MH prevalence was assessed by demographic, clinical, and ASC characteristics. RESULTS: During the study period, 31 of 17,092,765 discharges from ASCs had a recorded diagnosis of MH, yielding a prevalence of 0.18 per 100,000 discharges (95% confidence interval, 0.12-0.25). The prevalence of recorded MH diagnosis per discharge differed significantly across age groups and surgical procedure categories. All patients with a recorded diagnosis of MH were from hospital-based ASCs and were discharged alive from ASCs. CONCLUSIONS: The prevalence of recorded MH diagnosis in ASC patients is approximately 1 per 500,000 and varies considerably with surgical procedures. PMID- 26554463 TI - Anesthesiologist- and System-Related Risk Factors for Risk-Adjusted Pediatric Anesthesia-Related Cardiac Arrest. AB - BACKGROUND: Pediatric anesthesia-related cardiac arrest (ARCA) is an uncommon but potentially preventable adverse event. Infants and children with more severe underlying disease are at highest risk. We aimed to identify system- and anesthesiologist-related risk factors for ARCA. METHODS: We analyzed a prospectively collected patient cohort data set of anesthetics administered from 2000 to 2011 to children at a large tertiary pediatric hospital. Pre-procedure systemic disease level was characterized by ASA physical status (ASA-PS). Two reviewers independently reviewed cardiac arrests and categorized their anesthesia relatedness. Factors associated with ARCA in the univariate analyses were identified for reevaluation after adjustment for patient age and ASA-PS. RESULTS: Cardiac arrest occurred in 142 of 276,209 anesthetics (incidence 5.1/10,000 anesthetics); 72 (2.6/10,000 anesthetics) were classified as anesthesia-related. In the univariate analyses, risk of ARCA was much higher in cardiac patients and for anesthesiologists with lower annual caseload and/or fewer annual days delivering anesthetics (all P < 0.001). Anesthesiologists with the highest academic rank and years of experience also had higher odds of ARCA (P = 0.02). After risk adjustment for ASA-PS >= III and age <= 6 months, however, the association with lower annual days delivering anesthetics remained (P = 0.03), but the other factors were no longer significant. CONCLUSIONS: Case-mix explained most associations between higher risk of pediatric ARCA and anesthesiologist related variables at our institution, but the association with fewer annual days delivering anesthetics remained. Our findings highlight the need for rigorous adjustment for patient risk factors in anesthesia patient safety studies. PMID- 26554464 TI - A Mixed-Methods Approach to Understanding Community Participation in Community Health Needs Assessments. AB - CONTEXT: Nonprofit hospitals are exempt from paying taxes. To maintain this status, they must provide benefit to the community they serve. In an attempt to improve accountability to these communities and the federal government, the Patient Protection and Affordable Care Act of 2010 includes a provision that requires all nonprofit hospitals to conduct a community health needs assessment (CHNA) and implement strategies to address identified health priorities every 3 years. This Act's provision, operationalized by a regulation developed and enforced by the Internal Revenue Service, mandates the involvement of public health agencies and other community stakeholders in the completion of the CHNA. OBJECTIVE: To better understand community participation in nonprofit hospital directed community health assessment and health improvement planning activities. DESIGN: Using a 2-phased, mixed-methods study design, we (1) conducted content analysis of 95 CHNA/implementation plan reports and (2) interviewed hospital and health system key informants, consultants, and community stakeholders involved in CHNA and planning processes. Community participation was assessed in terms of types of stakeholders involved and the depth of their involvement. RESULTS: Our findings suggest that many hospitals engaged and involved community stakeholders in certain aspects of the assessment process, but very few engaged a broad array of community stakeholder and community members in meaningful participation throughout the CHNA and health improvement planning process. Vast improvements in community participation and collaborative assessment and planning can be made in future CHNAs. CONCLUSIONS: On the basis of the findings, recommendations are made for further research. Practice implications include expanding community engagement and participation by stakeholder and activity type and using a common community health improvement model that better aligns hospital CHNA processes and implementation strategies with other organizations and agencies. PMID- 26554465 TI - Two dimensional atomically thin MoS2 nanosheets and their sensing applications. AB - The extraordinary properties of layered graphene and its successful applications in electronics, sensors, and energy devices have inspired and renewed interest in other two-dimensional (2D) layered materials. Particularly, a semiconducting analogue of graphene, molybdenum disulfide (MoS2), has attracted huge attention in the last few years. With efforts in exfoliation and synthetic techniques, atomically thin films of MoS2 (single- and few-layer) have been recently prepared and characterized. 2D MoS2 nanosheets have properties that are distinct and complementary to those of graphene, making it more appealing for various applications. Unlike graphene with an indirect bandgap, the direct bandgap of single-layer MoS2 results in better semiconductor behavior as well as photoluminescence, suggesting its great suitability for electronic and optoelectronic applications. Compared to their applications in energy storage and optoelectronic devices, the use of MoS2 nanosheets as a sensing platform, especially for biosensing, is still largely unexplored. Here, we present a review of the preparation of 2D atomically thin MoS2 nanosheets, with an emphasis on their use in various sensing applications. PMID- 26554466 TI - OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development. AB - OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo developmental failure. Moreover OTX2 transfection revert this effect in OTX1(-/-) mice. The TA isoform of TP63, involved in Notch regulation pathway, has a critical function in the cochlear neuroepithelium differentiation. TAp63 positively regulates Hes5 and Atoh1 transcription. This pathway has been also demonstrated in p63(-/-) mice, and in patients p63 mutated, affected by Ectodermal Dysplasia (ED, OMIM 129810). These patients are affected by mild sensorineural deafness, most likely related to the mutation in p63 gene impairing the Notch pathway. We demonstrated the role of OTX2 on TAp63 regulation necessary for the correct formation of macular neuroepithelium and we confirmed the impairment of vestibular function caused by p63 mutations. Although the abnormalities found in our patient were still at a subclinical extent, aging could exacerbate this impairment and cause a decrease in quality of life. PMID- 26554468 TI - Risk Evaluation and Mitigation Strategy (REMS): FDA Perspective on What Physicians Need to Know. PMID- 26554471 TI - Dysuria: Evaluation and Differential Diagnosis in Adults. AB - The most common cause of acute dysuria is infection, especially cystitis. Other infectious causes include urethritis, sexually transmitted infections, and vaginitis. Noninfectious inflammatory causes include a foreign body in the urinary tract and dermatologic conditions. Noninflammatory causes of dysuria include medication use, urethral anatomic abnormalities, local trauma, and interstitial cystitis/bladder pain syndrome. An initial targeted history includes features of a local cause (e.g., vaginal or urethral irritation), risk factors for a complicated urinary tract infection (e.g., male sex, pregnancy, presence of urologic obstruction, recent procedure), and symptoms of pyelonephritis. Women with dysuria who have no complicating features can be treated for cystitis without further diagnostic evaluation. Women with vulvovaginal symptoms should be evaluated for vaginitis. Any complicating features or recurrent symptoms warrant a history, physical examination, urinalysis, and urine culture. Findings from the secondary evaluation, selected laboratory tests, and directed imaging studies enable physicians to progress through a logical evaluation and determine the cause of dysuria or make an appropriate referral. PMID- 26554472 TI - Diagnosis and Management of Common Types of Supraventricular Tachycardia. AB - Supraventricular tachycardia refers to rapid rhythms that originate and are sustained in atrial or atrioventricular node tissue above the bundle of His. The condition is caused by reentry phenomena or automaticity at or above the atrioventricular node, and includes atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, and atrial tachycardia. Most persons with these tachyarrhythmias have structurally normal hearts. Sudden onset of an accelerated heart rate can cause palpitations, light-headedness, chest discomfort, anxiety, dyspnea, or fatigue. The history is important to elicit episodic symptoms because physical examination and electrocardiography findings may be normal. A Holter monitor or event recorder may be needed to confirm the diagnosis. Vagal maneuvers may terminate the arrhythmia; if this fails, adenosine is effective in the acute setting. Calcium channel blockers (diltiazem or verapamil) or beta blockers (metoprolol) can be used acutely or as long-term therapy. Class Ic antiarrhythmics (flecainide or propafenone) can be used long term. Class Ia antiarrhythmics (quinidine, procainamide, or disopyramide) are used less often because of their modest effectiveness and adverse effects. Class III antiarrhythmics (amiodarone, sotalol, or dofetilide) are effective, but have potential adverse effects and should be administered in consultation with a cardiologist. Catheter ablation has a success rate of 95% and recurrence rate of less than 5%, and causes inadvertent heart block in less than 1% of patients. It is the preferred treatment for symptomatic patients with Wolff-Parkinson-White syndrome. PMID- 26554473 TI - Common Questions About Cognitive Behavior Therapy for Psychiatric Disorders. AB - Cognitive behavior therapy (CBT) is a time-limited, goal-oriented psychotherapy that has been extensively researched and has benefits in a number of psychiatric disorders, including anxiety, depression, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, autism, obsessive-compulsive and tic disorders, personality disorders, eating disorders, and insomnia. CBT uses targeted strategies to help patients adopt more adaptive patterns of thinking and behaving, which leads to positive changes in emotions and decreased functional impairments. Strategies include identifying and challenging problematic thoughts and beliefs, scheduling pleasant activities to increase environmental reinforcement, and extended exposure to unpleasant thoughts, situations, or physiologic sensations to decrease avoidance and arousal associated with anxiety eliciting stimuli. CBT can be helpful in the treatment of posttraumatic stress disorder by emphasizing safety, trust, control, esteem, and intimacy. Prolonged exposure therapy is a CBT technique that includes a variety of strategies, such as repeated recounting of the trauma and exposure to feared real-world situations. For attention-deficit/hyperactivity disorder, CBT focuses on establishing structures and routines, and clear rules and expectations within the home and classroom. Early intensive behavioral interventions should be initiated in children with autism before three years of age; therapy consists of 12 to 40 hours of intensive treatment per week, for at least one year. In many disorders, CBT can be used alone or in combination with medications. However, CBT requires a significant commitment from patients. Family physicians are well suited to provide collaborative care for patients with psychiatric disorders, in concert with cognitive behavior therapists. PMID- 26554477 TI - Unusual Erythematous and Infiltrated Plaque. PMID- 26554478 TI - Menstrual Concerns in an Adolescents with Disabilities. PMID- 26554480 TI - Effectiveness of Selective Serotonin Reuptake Inhibitors for Irritable Bowel Syndrome. PMID- 26554481 TI - Cognitive Behavior Therapy. PMID- 26554482 TI - Dysuria: What You Should Know About Burning or Stinging with Urination. PMID- 26554483 TI - Supraventricular Tachycardia: What You Should Know. PMID- 26554484 TI - Highly nucleophilic dipropanolamine chelated boron reagents for aryl transmetallation to iron complexes. AB - New aryl- and heteroarylboronate esters chelated by dipropanolamine are synthesised directly from boronic acids. The corresponding anionic borates are readily accessible by deprotonation and demonstrate an increase in hydrocarbyl nucleophilicity in comparison to other common borates. The new borates proved competent for magnesium or zinc additive-free, direct boron-to-iron hydrocarbyl transmetallations with well-defined iron(II) (pre)catalysts. The application of the new borate reagents in representative Csp(2)-Csp(3) cross-coupling led to almost exclusive homocoupling unless coupling is performed in the presence of a zinc additive. PMID- 26554485 TI - Easy Access to Hearing Health Care: Are We Closer Than We Think? PMID- 26554486 TI - Refining Stimulus Parameters in Assessing Infant Speech Perception Using Visual Reinforcement Infant Speech Discrimination: Sensation Level. AB - BACKGROUND: Speech perception measures have long been considered an integral piece of the audiological assessment battery. Currently, a prelinguistic, standardized measure of speech perception is missing in the clinical assessment battery for infants and young toddlers. Such a measure would allow systematic assessment of speech perception abilities of infants as well as the potential to investigate the impact early identification of hearing loss and early fitting of amplification have on the auditory pathways. PURPOSE: To investigate the impact of sensation level (SL) on the ability of infants with normal hearing (NH) to discriminate /a-i/ and /ba-da/ and to determine if performance on the two contrasts are significantly different in predicting the discrimination criterion. RESEARCH DESIGN: The design was based on a survival analysis model for event occurrence and a repeated measures logistic model for binary outcomes. The outcome for survival analysis was the minimum SL for criterion and the outcome for the logistic regression model was the presence/absence of achieving the criterion. Criterion achievement was designated when an infant's proportion correct score was >0.75 on the discrimination performance task. STUDY SAMPLE: Twenty-two infants with NH sensitivity participated in this study. There were 9 males and 13 females, aged 6-14 mo. DATA COLLECTION AND ANALYSIS: Testing took place over two to three sessions. The first session consisted of a hearing test, threshold assessment of the two speech sounds (/a/ and /i/), and if time and attention allowed, visual reinforcement infant speech discrimination (VRISD). The second session consisted of VRISD assessment for the two test contrasts (/a-i/ and /ba-da/). The presentation level started at 50 dBA. If the infant was unable to successfully achieve criterion (>0.75) at 50 dBA, the presentation level was increased to 70 dBA followed by 60 dBA. Data examination included an event analysis, which provided the probability of criterion distribution across SL. The second stage of the analysis was a repeated measures logistic regression where SL and contrast were used to predict the likelihood of speech discrimination criterion. RESULTS: Infants were able to reach criterion for the /a-i/ contrast at statistically lower SLs when compared to /ba-da/. There were six infants who never reached criterion for /ba-da/ and one never reached criterion for /a-i/. The conditional probability of not reaching criterion by 70 dB SL was 0% for /a i/ and 21% for /ba-da/. The predictive logistic regression model showed that children were more likely to discriminate the /a-i/ even when controlling for SL. CONCLUSIONS: Nearly all normal-hearing infants can demonstrate discrimination criterion of a vowel contrast at 60 dB SL, while a level of >=70 dB SL may be needed to allow all infants to demonstrate discrimination criterion of a difficult consonant contrast. PMID- 26554487 TI - Perception of Hearing Aid-Processed Speech in Individuals with Late-Onset Auditory Neuropathy Spectrum Disorder. AB - BACKGROUND: Auditory neuropathy spectrum disorder (ANSD) is a form of sensorineural hearing loss, causing severe deficits in speech perception. The perceptual problems of individuals with ANSD were attributed to their temporal processing impairment rather than to reduced audibility. This rendered their rehabilitation difficult using hearing aids. Although hearing aids can restore audibility, compression circuits in a hearing aid might distort the temporal modulations of speech, causing poor aided performance. Therefore, hearing aid settings that preserve the temporal modulations of speech might be an effective way to improve speech perception in ANSD. PURPOSE: The purpose of the study was to investigate the perception of hearing aid-processed speech in individuals with late-onset ANSD. RESEARCH DESIGN: A repeated measures design was used to study the effect of various compression time settings on speech perception and perceived quality. STUDY SAMPLE: Seventeen individuals with late-onset ANSD within the age range of 20-35 yr participated in the study. DATA COLLECTION AND ANALYSIS: The word recognition scores (WRSs) and quality judgment of phonemically balanced words, processed using four different compression settings of a hearing aid (slow, medium, fast, and linear), were evaluated. The modulation spectra of hearing aid-processed stimuli were estimated to probe the effect of amplification on the temporal envelope of speech. Repeated measures analysis of variance and post hoc Bonferroni's pairwise comparisons were used to analyze the word recognition performance and quality judgment. RESULTS: The comparison between unprocessed and all four hearing aid-processed stimuli showed significantly higher perception using the former stimuli. Even though perception of words processed using slow compression time settings of the hearing aids were significantly higher than the fast one, their difference was only 4%. In addition, there were no significant differences in perception between any other hearing aid-processed stimuli. Analysis of the temporal envelope of hearing aid processed stimuli revealed minimal changes in the temporal envelope across the four hearing aid settings. In terms of quality, the highest number of individuals preferred stimuli processed using slow compression time settings. Individuals who preferred medium ones followed this. However, none of the individuals preferred fast compression time settings. Analysis of quality judgment showed that slow, medium, and linear settings presented significantly higher preference scores than the fast compression setting. CONCLUSIONS: Individuals with ANSD showed no marked difference in perception of speech that was processed using the four different hearing aid settings. However, significantly higher preference, in terms of quality, was found for stimuli processed using slow, medium, and linear settings over the fast one. Therefore, whenever hearing aids are recommended for ANSD, those having slow compression time settings or linear amplification may be chosen over the fast (syllabic compression) one. In addition, WRSs obtained using hearing aid-processed stimuli were remarkably poorer than unprocessed stimuli. This shows that processing of speech through hearing aids might have caused a large reduction of performance in individuals with ANSD. However, further evaluation is needed using individually programmed hearing aids rather than hearing aid-processed stimuli. PMID- 26554488 TI - What Can We Learn about Auditory Processing from Adult Hearing Questionnaires? AB - BACKGROUND: Questionnaires addressing auditory disability may identify and quantify specific symptoms in adult patients with listening difficulties. PURPOSE: (1) To assess validity of the Speech, Spatial, and Qualities of Hearing Scale (SSQ), the (Modified) Amsterdam Inventory for Auditory Disability (mAIAD), and the Hyperacusis Questionnaire (HYP) in adult patients experiencing listening difficulties in the presence of a normal audiogram. (2) To examine which individual questionnaire items give the worse scores in clinical participants with an auditory processing disorder (APD). RESEARCH DESIGN: A prospective correlational analysis study. STUDY SAMPLE: Clinical participants (N = 58) referred for assessment because of listening difficulties in the presence of normal audiometric thresholds to audiology/ear, nose, and throat or audiovestibular medicine clinics. Normal control participants (N = 30). DATA COLLECTION AND ANALYSIS: The mAIAD, HYP, and the SSQ were administered to a clinical population of nonneurological adults who were referred for auditory processing (AP) assessment because of hearing complaints, in the presence of normal audiogram and cochlear function, and to a sample of age-matched normal hearing controls, before the AP testing. Clinical participants with abnormal results in at least one ear and in at least two tests of AP (and at least one of these tests to be nonspeech) were classified as clinical APD (N = 39), and the remaining (16 of whom had a single test abnormality) as clinical non-APD (N = 19). RESULTS: The SSQ correlated strongly with the mAIAD and the HYP, and correlation was similar within the clinical group and the normal controls. All questionnaire total scores and subscores (except sound distinction of mAIAD) were significantly worse in the clinical APD versus the normal group, while questionnaire total scores and most subscores indicated greater listening difficulties for the clinical non-APD versus the normal subgroups. Overall, the clinical non-APD group tended to give better scores than the APD in all questionnaires administered. Correlation was strong for the worse-ear gaps-in noise threshold with the SSQ, mAIAD, and HYP; strong to moderate for the speech in babble and left-ear dichotic digit test scores (at p < 0.01); and weak to moderate for the remaining AP tests except the frequency pattern test that did not correlate. The worse-scored items in all three questionnaires concerned speech-in-noise questions. This is similar to worse-scored items by hearing impaired participants as reported in the literature. Worse-scored items of the clinical group also included quality aspects of listening questions from the SSQ, which most likely pertain to cognitive aspects of listening, such as ability to ignore other sounds and listening effort. CONCLUSIONS: Hearing questionnaires may help assess symptoms of adults with APD. The listening difficulties and needs of adults with APD to some extent overlap with those of hearing-impaired listeners, but there are significant differences. The correlation of the gaps-in-noise and duration pattern (but not frequency pattern) tests with the questionnaire scores indicates that temporal processing deficits may play an important role in clinical presentation. PMID- 26554489 TI - Benefits of Nonlinear Frequency Compression in Adult Hearing Aid Users. AB - BACKGROUND: Frequency-lowering (FL) algorithms are an alternative method of providing access to high-frequency speech cues. There is currently a lack of independent research addressing: (1) what functional, measureable benefits FL provides; (2) which, if any, FL algorithm provides the maximum benefit, (3) how to clinically program algorithms, and (4) how to verify algorithm settings. PURPOSE: Two experiments were included in this study. The purpose of Experiment 1 was to (1) determine if a commercially available nonlinear frequency compression (NLFC) algorithm provides benefit as measured by improved speech recognition in noise when fit and verified using standard clinical procedures; and (2) evaluate the impact of acclimatization. The purpose of Experiment 2 was to (1) evaluate the benefit of using enhanced verification procedures to systematically determine the optimal application of a prototype NLFC algorithm, and (2) determine if the optimized prototype NLFC settings provide benefit as measured by improved speech recognition in quiet and in noise. RESEARCH DESIGN: A single-blind, within participant repeated measures design in which participants served as their own controls. STUDY SAMPLE: Experiment 1 included 26 participants with a mean age of 68.3 yr and Experiment 2 included 37 participants with a mean age of 68.8 yr. Participants were recruited from the Audiology and Speech Pathology Center at Walter Reed National Military Medical Center in Bethesda, MD. INTERVENTION: Participants in Experiment 1 wore bilateral commercially available hearing aids fit using standard clinical procedures and clinician expertise. Participants in Experiment 2 wore a single prototype hearing aid for which FL settings were systematically examined to determine the optimum application. In each experiment, FL-On versus FL-Off settings were examined in a variety of listening situations to determine benefit and possible implications. DATA COLLECTION AND ANALYSIS: In Experiment 1, speech recognition measures using the QuickSIN and Modified Rhyme Test stimuli were obtained at initial bilateral fitting and 3-5 weeks later during a follow-up visit. In Experiment 2, Modified Rhyme Test, /se/, /?e/ consonant discrimination task, and dual-task cognitive load speech recognition performance measures were conducted. Participants in Experiment 2 received four different systematic hearing aid programs during an initial visit and speech recognition data were collected over 2-3 follow-up sessions. RESULTS: Some adults with hearing loss obtained small-to-moderate benefits from implementation of FL, while others maintained performance without detriment in both experiments. There was no significant difference among FL-On settings systematically obtained in Experiment 2. There was a modest but significant age effect in listeners of both experiments that indicated older listeners (>65 yr) might benefit more on average from FL than younger listeners. In addition, there were reliable improvements in the intelligibility of the phonemes /n/ and /b/ for both groups, and /d/ for older listeners from the FL in both experiments. CONCLUSIONS: Although the optimum settings, application, and benefits of FL remain unclear at this time, there does not seem to be degradation in listener performance when FL is activated. The benefits of FL should be explored in older adult (>65 yr) listeners, as they tended to benefit more from FL applications. PMID- 26554490 TI - Evaluation of a BICROS System with a Directional Microphone in the Receiver and Transmitter. AB - BACKGROUND: The bilateral contralateral routing of signals (BICROS) system has provided limited benefit for speech recognition in noise for patients with asymmetric sensorineural hearing loss, even when an automatic adaptive multichannel directional microphone (DM) is in the receiver (Rx) and an omnidirectional microphone (OM) is in the transmitter (Tx). A recent BICROS system was introduced that can be programmed with a DM in the Rx and an OM or a DM in the Tx. PURPOSE: To examine if significant differences in sentence recognition in noise and subjective preferences are present between an OM and an adaptive broadband DM programmed in the Tx of a BICROS system with an automatic adaptive multichannel DM programmed in the Rx. RESEARCH DESIGN: A randomized crossover single-blind design was used to assess differences between the OM and DM programmed in the Tx. STUDY SAMPLE: Eighteen adult experienced BICROS system users were recruited. DATA COLLECTION AND ANALYSIS: The BICROS system was fit using real-ear insertion gain measures. The Tx was programmed with an OM and a DM and the Rx was always programmed with an automatic adaptive multichannel DM. The order of microphone condition in the Tx was counterbalanced. Participants acclimatized to the BICROS system for 4 weeks and returned and completed the Abbreviated Profile of Hearing Aid Benefit (APHAB) for the respective microphone condition. The Tx was then programmed with the other microphone condition and participants acclimatized for another four weeks. At the final visit, the APHAB was completed for the respective microphone condition. After eight weeks of acclimatization, Hearing in Noise Test sentences were presented in the R-SpaceTM system with the Tx in either the OM or DM condition for three listening conditions: (1) speech from 90 degrees to the Rx and noise from 0 degrees , 90 degrees , and 180 degrees to the Tx (Sp Rx/N Tx), (2) speech from 90 degrees to the Tx and noise from 0 degrees , 90 degrees , and 180 degrees to the Rx (Sp Tx/N Rx), and (3) speech from 0 degrees and noise from eight surrounding loudspeakers separated by 45 degrees (diffuse). RESULTS: A two-factor repeated measures analysis of variance revealed no significant differences between the OM and DM microphone conditions for Sp Rx/N Tx listening condition. A significant mean disadvantage of 1.9 dB (p < 0.01) was revealed for the DM compared to the OM for Sp Tx/N Rx listening condition and a mean advantage of 2.6 dB (p < 0.001) for the DM compared to the OM in a diffuse listening condition. There were no significant differences in the APHAB aided problem and resulting benefit scores between the OM and DM for the following subscales: ease of communication, background noise, reverberation, and aversiveness of sounds. CONCLUSIONS: No significant differences were revealed between OM and DM for Sp Rx/N Tx. The DM performed significantly poorer than OM for the Sp Tx/N Rx listening condition. Results revealed significant benefit for the DM compared to OM for the diffuse listening condition. No significant differences were revealed between the OM and DM on the APHAB. PMID- 26554491 TI - Construct Validity of the Ecological Momentary Assessment in Audiology Research. AB - BACKGROUND: Ecological momentary assessment (EMA) is a methodology involving repeated assessments/surveys to collect data describing respondents' current or very recent experiences and related contexts in their natural environments. The use of EMA in audiology research is growing. PURPOSE: This study examined the construct validity (i.e., the degree to which a measurement reflects what it is intended to measure) of EMA in terms of measuring speech understanding and related listening context. Experiment 1 investigated the extent to which individuals can accurately report their speech recognition performance and characterize the listening context in controlled environments. Experiment 2 investigated whether the data aggregated across multiple EMA surveys conducted in uncontrolled, real-world environments would reveal a valid pattern that was consistent with the established relationships between speech understanding, hearing aid use, listening context, and lifestyle. RESEARCH DESIGN: This is an observational study. STUDY SAMPLE: Twelve and twenty-seven adults with hearing impairment participated in Experiments 1 and 2, respectively. DATA COLLECTION AND ANALYSIS: In the laboratory testing of Experiment 1, participants estimated their speech recognition performance in settings wherein the signal-to-noise ratio was fixed or constantly varied across sentences. In the field testing the participants reported the listening context (e.g., noisiness level) of several semicontrolled real-world conversations. Their reports were compared to (1) the context described by normal-hearing observers and (2) the background noise level measured using a sound level meter. In Experiment 2, participants repeatedly reported the degree of speech understanding, hearing aid use, and listening context using paper-and-pencil journals in their natural environments for 1 week. They also carried noise dosimeters to measure the sound level. The associations between (1) speech understanding, hearing aid use, and listening context, (2) dosimeter sound level and self-reported noisiness level, and (3) dosimeter data and lifestyle quantified using the journals were examined. RESULTS: For Experiment 1, the reported and measured speech recognition scores were highly correlated across all test conditions (r = 0.94 to 0.97). The field testing results revealed that most listening context properties reported by the participants were highly consistent with those described by the observers (74-95% consistency), except for noisiness rating (58%). Nevertheless, higher noisiness rating was associated with higher background noise level. For Experiment 2, the EMA results revealed several associations: better speech understanding was associated with the use of hearing aids, front-located speech, and lower dosimeter sound level; higher noisiness rating was associated with higher dosimeter sound level; listeners with more diverse lifestyles tended to have higher dosimeter sound levels. CONCLUSIONS: Adults with hearing impairment were able to report their listening experiences, such as speech understanding, and characterize listening context in controlled environments with reasonable accuracy. The pattern of the data aggregated across multiple EMA surveys conducted in a wide range of uncontrolled real-world environment was consistent with the established knowledge in audiology. The two experiments suggested that, regarding speech understanding and related listening contexts, EMA reflects what it is intended to measure, supporting its construct validity in audiology research. PMID- 26554494 TI - Sulfate Radical Photogeneration Using Fe-EDDS: Influence of Critical Parameters and Naturally Occurring Scavengers. PMID- 26554495 TI - Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery. AB - Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy. PMID- 26554497 TI - Improved Corrosion Resistance and Mechanical Properties of CrN Hard Coatings with an Atomic Layer Deposited Al2O3 Interlayer. AB - A new approach was adopted to improve the corrosion resistance of CrN hard coatings by inserting a Al2O3 layer through atomic layer deposition. The influence of the addition of a Al2O3 interlayer, its thickness, and the position of its insertion on the microstructure, surface roughness, corrosion behavior, and mechanical properties of the coatings was investigated. The results indicated that addition of a dense atomic layer deposited Al2O3 interlayer led to a significant decrease in the average grain size and surface roughness and to greatly improved corrosion resistance and corrosion durability of CrN coatings while maintaining their mechanical properties. Increasing the thickness of the Al2O3 interlayer and altering its insertion position so that it was near the surface of the coating also resulted in superior performance of the coating. The mechanism of this effect can be explained by the dense Al2O3 interlayer acting as a good sealing layer that inhibits charge transfer, diffusion of corrosive substances, and dislocation motion. PMID- 26554496 TI - Using an eHealth Intervention to Stimulate Health Behavior for the Prevention of Cognitive Decline in Dutch Adults: A Study Protocol for the Brain Aging Monitor. AB - BACKGROUND: Internet-delivered intervention programs are an effective way of changing health behavior in an aging population. The same population has an increasing number of people with cognitive decline or cognitive impairments. Modifiable lifestyle risk factors such as physical activity, nutrition, smoking, alcohol consumption, sleep, and stress all influence the probability of developing neurodegenerative diseases such as Alzheimer's disease. OBJECTIVE: This study aims to answer two questions: (1) Is the use of a self-motivated, complex eHealth intervention effective in changing multiple health behaviors related to cognitive aging in Dutch adults in the work force, especially those aged 40 and over? and (2) Does this health behavior change result in healthier cognitive aging patterns and contribute to preventing or delaying future onset of neurodegenerative syndromes? METHODS: The Brain Aging Monitor study uses a quasi experimental 2-year pre-posttest design. The Brain Aging Monitor is an online, self-motivated lifestyle intervention program. Recruitment is done both in medium to large organizations and in the Dutch general population over the age of 40. The main outcome measure is the relationship between lifestyle change and cognitive aging. The program uses different strategies and modalities such as Web content, email, online newsletters, and online games to aid its users in behavior change. To build self-regulatory skills, the Brain Aging Monitor offers its users goal-setting activities, skill-building activities, and self-monitoring. RESULTS: Study results are expected to be published in early 2016. CONCLUSIONS: This study will add to the body of evidence on the effectiveness of eHealth intervention programs with the combined use of state-of-the-art applied games and established behavior change techniques. This will lead to new insights on how to use behavior change techniques and theory in multidimensional lifestyle eHealth research, and how these techniques and theories apply when they are used in a setting where no professional back-end is available. TRIAL REGISTRATION: Nederlands Trial Register: NTR4144; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4144 (Archived by WebCite at http://www.webcitation.org/6cZzwZSg3). PMID- 26554498 TI - Ultrafast, Light-Induced Electron Transfer in a Perylene Diimide Chromophore Donor Assembly on TiO2. AB - Surface-bound, perylenediimide (PDI)-based molecular assemblies have been synthesized on nanocrystalline TiO2 by reaction of a dianhydride with a surface bound aniline and succinimide bonding. In a second step, the Fe(II) polypyridyl complex [Fe(II)(tpy-PhNH2)2](2+) was added to the outside of the film, also by succinimide bonding. Ultrafast transient absorption measurements in 0.1 M HClO4 reveal that electron injection into TiO2 by (1)PDI* does not occur, but rather leads to the ultrafast formation of the redox-separated pair PDI(*+),PDI(*-), which decays with complex kinetics (tau1 = 0.8 ps, tau2 = 15 ps, and tau3 = 1500 ps). With the added Fe(II) polypyridyl complex, rapid (<25 ps) oxidation of Fe(II) by the PDI(*+),PDI(*-) redox pair occurs to give Fe(III),PDI(*-) persisting for >400 MUs in the film environment. PMID- 26554499 TI - Safety inspections in construction sites: A systems thinking perspective. AB - Although safety inspections carried out by government officers are important for the prevention of accidents, there is little in-depth knowledge on their outcomes and processes leading to these. This research deals with this gap by using systems thinking (ST) as a lens for obtaining insights into safety inspections in construction sites. Thirteen case studies of sites with prohibited works were carried out, discussing how four attributes of ST were used in the inspections. The studies were undertaken over 6 years, and sources of evidence involved participant observation, direct observations, analysis of documents and interviews. Two complementary ways for obtaining insights into inspections, based on ST, were identified: (i) the design of the study itself needs to be in line with ST; and (ii) data collection and analysis should focus on the agents involved in the inspections, the interactions between agents, the constraints and opportunities faced by agents, the outcomes of interactions, and the recommendations for influencing interactions. PMID- 26554500 TI - Drainage in a rising foam. AB - Rising foams created by continuously blowing gas into a surfactant solution are widely used in many technical processes, such as flotation. The prediction of the liquid fraction profile in such flowing foams is of particular importance since this parameter controls the stability and the rheology of the final product. Using drift flux analysis and recently developed semi-empirical expressions for foam permeability and osmotic pressure, we build a model predicting the liquid fraction profile as a function of height. The theoretical profiles are very different if the interfaces are considered as mobile or rigid, but all of our experimental profiles are described by the model with mobile interfaces. Even the systems with dodecanol are well known to behave as rigid in forced drainage experiments. This is because in rising foams the liquid fraction profile is fixed by the flux at the bottom of the foam. Here the foam is wet with higher permeability and the interfaces are not in equilibrium. These results demonstrate once again that it is not only the surfactant system that controls the mobility of the interface, but also the hydrodynamic problem under consideration. For example liquid flow through the foam during generation or in forced drainage is intrinsically different. PMID- 26554501 TI - Removal of Particulate Matter Emissions from a Vehicle Using a Self-Powered Triboelectric Filter. AB - Particulate matter (PM) pollution from automobile exhaust has become one of the main pollution sources in urban environments. Although the diesel particulate filter has been used in heavy diesel vehicles, there is no particulate filter for most gasoline cars or light-duty vehicles because of high cost. Here, we introduce a self-powered triboelectric filter for removing PMs from automobile exhaust fumes using the triboelectrification effect. The finite element simulation reveals that the collision or friction between PTFE pellets and electrodes can generate large triboelectric charges and form a space electric field as high as 12 MV/m, accompanying an open-circuit voltage of ~6 kV between the two electrodes, which is comparable to the measured value of 3 kV. By controlling the vibration frequency and fill ratio of pellets, more than 94% PMs in aerosol can be removed using the high electric field in the triboelectric filter. In real automobile exhaust fumes, the triboelectic filter has a mass collection efficiency of ~95.5% for PM2.5 using self-vibration of the tailpipe. PMID- 26554502 TI - Spectroscopic Evidence of Nanodomains in THF/RTIL Mixtures: Spectroelectrochemical and Voltammetric Study of Nickel Porphyrins. AB - The presence and effect of RTIL nanodomains in molecular solvent/RTIL mixture were investigated by studying the spectroelectrochemistry and voltammetry of nickel octaethylporphyrin (Ni(OEP)) and nickel octaethylporphinone (Ni(OEPone)). Two oxidation and 2-3 reduction redox couples were observed, and the UV-visible spectra of all stable products in THF and RTIL mixtures were obtained. The E degrees values for the reduction couples that were studied were linearly correlated with the Gutmann acceptor number, as well as the difference in the E degrees values between the first two waves (DeltaE12 degrees = |E1 degrees - E2 degrees |). The DeltaE12 degrees for the reduction was much more sensitive to the %RTIL in the mixture than the oxidation, indicating a strong interaction between the RTIL and the anion or dianion. The shifts in the E degrees values were significantly different between Ni(OEP) and Ni(OEPone). For Ni(OEP), the E1 degrees values were less sensitive to the %RTIL than were observed for Ni(OEPone). Variations in the diffusion coefficients of Ni(OEP) and Ni(OEPone) as a function of %RTIL were also investigated, and the results were interpreted in terms of RTIL nanodomains. To observe the effect of solvation on the metalloporphyrin, Ni(OEPone) was chosen because it contains a carbonyl group that can be easily observed in infrared spectroelectrochemistry. It was found that the nuCO band was very sensitive to the solvent environment, and two carbonyl bands were observed for Ni(OEPone)(-) in mixed THF/RTIL solutions. The higher energy band was attributed to the reduced product in THF, and the lower energy band attributed to the reduced product in the RTIL nanophase. The second band could be observed with as little as 5% of the RTIL. No partitioning of Ni(OEPone)(+) into the RTIL nanodomain was observed. DFT calculations were carried out to characterize the product of the first reduction. These results provide strong direct evidence of the presence of nanodomains in molecular solvent/RTIL mixtures. PMID- 26554503 TI - MAKING SENSE OF OUR VARIATION. AB - Each human genome differs by millions of sequence variants, but which of these differences are important in human biology and disease? Jeffrey Perkel takes a look at the how scientists are identifying and cataloging important genetic variation. PMID- 26554504 TI - Slide Set: Reproducible image analysis and batch processing with ImageJ. AB - Most imaging studies in the biological sciences rely on analyses that are relatively simple. However, manual repetition of analysis tasks across multiple regions in many images can complicate even the simplest analysis, making record keeping difficult, increasing the potential for error, and limiting reproducibility. While fully automated solutions are necessary for very large data sets, they are sometimes impractical for the small- and medium-sized data sets common in biology. Here we present the Slide Set plugin for ImageJ, which provides a framework for reproducible image analysis and batch processing. Slide Set organizes data into tables, associating image files with regions of interest and other relevant information. Analysis commands are automatically repeated over each image in the data set, and multiple commands can be chained together for more complex analysis tasks. All analysis parameters are saved, ensuring transparency and reproducibility. Slide Set includes a variety of built-in analysis commands and can be easily extended to automate other ImageJ plugins, reducing the manual repetition of image analysis without the set-up effort or programming expertise required for a fully automated solution. PMID- 26554505 TI - Into the depths: Techniques for in vitro three-dimensional microtissue visualization. AB - Three-dimensional (3-D) in vitro platforms have been shown to closely recapitulate human physiology when compared with conventional two-dimensional (2 D) in vitro or in vivo animal model systems. This confers a substantial advantage in evaluating disease mechanisms, pharmaceutical drug discovery, and toxicity testing. Despite the benefits of 3-D cell culture, limitations in visualization and imaging of 3-D microtissues present significant challenges. Here we optimized histology and microscopy techniques to overcome the constraints of 3-D imaging. For morphological assessment of 3-D microtissues of several cell types, different time points, and different sizes, a two-step glycol methacrylate embedding protocol for evaluating 3-D microtissues produced using agarose hydrogels improved resolution of nuclear and cellular histopathology characteristic of cell death and proliferation. Additional immunohistochemistry, immunofluorescence, and in situ immunostaining techniques were successfully adapted to these microtissues and enhanced by optical clearing. Utilizing the Clear(T2) protocol greatly increased fluorescence signal intensity, imaging depth, and clarity, allowing for more complete confocal fluorescence microscopy imaging of these 3-D microtissues compared with uncleared samples. The refined techniques presented here address the key challenges associated with 3-D imaging, providing new and alternative methods in evaluating disease pathogenesis, delineating toxicity pathways, and enhancing the versatility of 3-D in vitro testing systems in pharmacological and toxicological applications. PMID- 26554506 TI - Development of a novel hepatitis B virus encapsidation detection assay by viral nucleocapsid-captured quantitative RT-PCR. AB - After encapsidation, where pregenomic RNA (pgRNA) is packaged into viral nucleocapsids, hepatitis B virus (HBV) uses the pgRNA as a template to replicate its DNA genome by reverse transcription. To date, there are only two encapsidation detection methods for evaluating the amount of pgRNA packaged into nucleocapsids: (i) the RNase protection assay and (ii) the native agarose gel electrophoresis assay. However, these methods are complex and laborious because they require multiple pgRNA purification steps followed by detection via an isotope-labeled probe. Moreover, both assays are unsuitable for evaluating a large number of antiviral agents in a dose-dependent manner. To overcome these limitations, we devised a novel HBV encapsidation assay in a 96-well plate format using nucleocapsid capture plates coated with an anti-HBV core (HBc) antibody, usually employed in enzyme-linked immunosorbent assays, to immobilize viral nucleocapsids. Viral pgRNA is then detected by quantitative RT-PCR (RT-qPCR). This strategy allows fast, convenient, and quantitative analysis of multiple viral RNA samples to evaluate encapsidation inhibitors. Furthermore, our protocol is potentially suitable for high-throughput screening (HTS) of compounds targeting HBV pgRNA encapsidation. PMID- 26554507 TI - Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy. AB - The ability to image the entire adult mouse heart at high resolution in 3-D would provide enormous advantages in the study of heart disease. However, a technique for imaging nuclear/cellular detail as well as the overall structure of the entire heart in 3-D with minimal effort is lacking. To solve this problem, we modified the benzyl alcohol:benzyl benzoate (BABB) clearing technique by labeling mouse hearts with periodic acid Schiff (PAS) stain. We then imaged the hearts with a combination of two-photon fluorescence microscopy and automated tile-scan imaging/stitching. Utilizing the differential spectral properties of PAS, we could identify muscle and nuclear compartments in the heart. We were also able to visualize the differences between a 3-month-old normal mouse heart and a mouse heart that had undergone heart failure due to the expression of cardiac myosin binding protein-C (cMyBP-C) gene mutation (t/t). Using 2-D and 3-D morphometric analysis, we found that the t/t heart had anomalous ventricular shape, volume, and wall thickness, as well as a disrupted sarcomere pattern. We further validated our approach using decellularized hearts that had been cultured with 3T3 fibroblasts, which were tracked using a nuclear label. We were able to detect the 3T3 cells inside the decellularized intact heart tissue, achieving nuclear/cellular resolution in 3-D. The combination of labeling, clearing, and two-photon microscopy together with tiling eliminates laborious and time consuming physical sectioning, alignment, and 3-D reconstruction. PMID- 26554508 TI - Subcellular object quantification with Squassh3C and SquasshAnalyst. AB - Quantitative image analysis plays an important role in contemporary biomedical research. Squassh is a method for automatic detection, segmentation, and quantification of subcellular structures and analysis of their colocalization. Here we present the applications Squassh3C and SquasshAnalyst. Squassh3C extends the functionality of Squassh to three fluorescence channels and live-cell movie analysis. SquasshAnalyst is an interactive web interface for the analysis of Squassh3C object data. It provides segmentation image overview and data exploration, figure generation, object and image filtering, and a statistical significance test in an easy-to-use interface. The overall procedure combines the Squassh3C plug-in for the free biological image processing program ImageJ and a web application working in conjunction with the free statistical environment R, and it is compatible with Linux, MacOS X, or Microsoft Windows. Squassh3C and SquasshAnalyst are available for download at www.psi.ch/lbr/SquasshAnalystEN/SquasshAnalyst.zip. PMID- 26554509 TI - Autophagy: The missing link in diabetic neuropathy? AB - Autophagy is a dynamic process which plays an important role in cellular homeostasis through recycling of damaged proteins and organelles. Chronic hyperglycemia associated with diabetes is known to impair the cellular autophagic pathways to a varied extent in some of the diabetic complications. But the role of autophagy driven quality control of proteins and the cellular organelles has been understudied in diabetic complications including neuropathy (DN). The present article hypothesizes that enhancing autophagy in neuronal cells may help them to get rid of bioenergetic crisis, necrosis, apoptosis associated with DN. Some forms of autophagic turnover also help to maintain integral, healthy mitochondria, malfunctioning of which produces cellular reactive oxygen species and may prevent accumulation of damaged protein aggregates. Involvement of various energy derived metabolic, cellular death pathways and oxidative stress in the pathogenesis of DN and how autophagy may halts the progression of DN has been discussed with supporting literature. PMID- 26554510 TI - Influences underlying family food choices in mothers from an economically disadvantaged community. AB - PURPOSE: The purpose of this qualitative study was to explore the perceptions and attitudes that underlie food choices, and, the impact of a school-based healthy eating intervention in mothers from an economically-disadvantaged community. The aim of the intervention was to educate children to act as 'health messengers' to their families. METHOD: Sixteen semi-structured phone interviews were conducted with mothers with four receiving a second interview. Interviews were conducted following their child's participation in a six-week after school healthy cooking intervention. RESULTS: Thematic content analysis revealed four main themes: Cost and budget influence on food choices, diversity in household rules controlling food, role of socialisation on diet, and improved cooking skills and confidence to make homemade meals. The interview findings demonstrated the positive influence of the after-school cooking intervention on children and their families in cooking skills, promoting healthier cooking methods and increasing confidence to prepare homemade meals. CONCLUSIONS: The findings demonstrated the wider economic and social influences on food choices and eating practices. Socialisation into, and strong cultural norms around, eating habits were significant influences on family diet and on parental decisions underpinning food choices and attitudes towards the control of food within the family. The intervention was perceived to be successful in terms of improving nutritional knowledge, cooking skills and increasing confidence to make healthy and tasty homemade meals. The study demonstrates the importance of parental involvement in school-based interventions if improvements in healthy eating are to be evidenced at the family level and maintained. PMID- 26554511 TI - Working safely with robot workers: Recommendations for the new workplace. AB - The increasing use of robots in performing tasks alongside or together with human co-workers raises novel occupational safety and health issues. The new 21st century workplace will be one in which occupational robotics plays an increasing role. This article describes the increasing complexity of robots and proposes a number of recommendations for the practice of safe occupational robotics. PMID- 26554512 TI - Low levels of graphene and graphene oxide inhibit cellular xenobiotic defense system mediated by efflux transporters. AB - Low levels of graphene and graphene oxide (GO) are considered to be environmentally safe. In this study, we analyzed the potential effects of graphene and GO at relatively low concentrations on cellular xenobiotic defense system mediated by efflux transporters. The results showed that graphene (<0.5 MUg/mL) and GO (<20 MUg/mL) did not decrease cell viability, generate reactive oxygen species, or disrupt mitochondrial function. However, graphene and GO at the nontoxic concentrations could increase calcein-AM (CAM, an indicator of membrane ATP-binding cassette (ABC) transporter) activity) accumulation, indicating inhibition of ABC transporters' efflux capabilities. This inhibition was observed even at 0.005 MUg/mL graphene and 0.05 MUg/mL GO, which are 100 times and 400 times lower than their lowest toxic concentration from cytotoxicity experiments, respectively. The inhibition of ABC transporters significantly increased the toxicity of paraquat and arsenic, known substrates of ABC transporters. The inhibition of ABC transporters was found to be based on graphene and GO damaging the plasma membrane structure and fluidity, thus altering functions of transmembrane ABC transporters. This study demonstrates that low levels of graphene and GO are not environmentally safe since they can significantly make cell more susceptible to other xenobiotics, and this chemosensitizing activity should be considered in the risk assessment of graphene and GO. PMID- 26554514 TI - Two very different types of clinical importance. PMID- 26554513 TI - Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence. AB - The limbal epithelial stem cell (LESC) hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC) hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks. PMID- 26554515 TI - Upregulation of CCL2 via ATF3/c-Jun interaction mediated the Bortezomib-induced peripheral neuropathy. AB - Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In present study, we found that application of BTZ at 0.4 mg/kg for consecutive 5 days significantly increased the expression of CCL2 in DRG, and intrathecal administration of neutralizing antibody against CCL2 inhibited the mechanical allodynia induced by BTZ. We also found an increased expression of c-Jun in DRG, and that inhibition of c-Jun signaling prevented the CCL2 upregulation and mechanical allodynia in the rats treated with BTZ. Furthermore, the results with luciferase assay in vitro and ChIP assay in vivo showed that c-Jun might be essential for BTZ-induced CCL2 upregulation via binding directly to the specific position of the ccl2 promoter. In addition, the present results showed that an upregulated expression of ATF3 was co-expressed with c-Jun in the DRG neurons, and the enhanced interaction between c-Jun and ATF3 was observed in DRG in the rats treated with BTZ. Importantly, pretreatment with ATF3 siRNA significantly inhibited the recruitment of c-Jun to the ccl2 promoter in the rats treated with BTZ. Taken together, these findings suggested that upregulation of CCL2 resulting from the enhanced interaction between c-Jun and ATF3 in DRG contributed to BTZ induced mechanical allodynia. PMID- 26554516 TI - Effects of catecholaminergic nerve lesion on endometrial development during early pregnancy in Mice. AB - Maternal stress is common during pregnancy and the postnatal period. This stress typically activates the sympathetic nervous system which releases catecholamines. This study explored the influence of sympathectomy by using neurotoxin 6 hydroxydopamine (6-OHDA) on embryo implantation, and investigated the influence mechanism of sympathectomy on reconstruction of endometrial structure during early pregnancy. In the 6-OHDA-treated mice, uterine glands in the endometrium developed poorly, and the gland epithelia were arranged irregularly during early pregnancy. Furthermore, vacuoles, karyopykosis and plasmarrhexis appeared in some gland epithelia. The percentage of uterine glands and the density of proliferating cell nuclear antigen (PCNA) positivity were dramatically decreased, and Fas ligand (FasL) expression was decreased in cells from pregnancy days 5-9 (E5-9) in the treated group. Antioxidant enzyme activity levels in uteri were lower but the malondialdehyde (MDA) levels were higher in the 6-OHDA mice than those in the control mice at E5-9. Similarly, the number of inducible nitric oxide synthase (iNOS) positive cells was significantly increased during early pregnancy following treatment with 6-OHDA. Our results have indicated that peripheral catecholaminergic nerve lesions induced by 6-OHDA cause adverse pregnancy outcomes through disruption of endometrial gland development, which increases oxidative stress and iNOS expression in the endometrium. Thus, catecholaminergic nerves might favourably influence blastocyst implantation, foetal survival and development during early pregnancy by oxidative state regulation and endometrial gland reconstruction. PMID- 26554517 TI - A method for continuous and stable perfusion of tissue and single cell preparations with accurate concentrations of volatile anaesthetics. AB - BACKGROUND: It is difficult to design a system to reliably deliver volatile anaesthetics such as halothane or isoflurane to in vitro preparations such as tissues or cells cultures: the very volatility of the drugs means that they can rapidly dissipate from even carefully-prepared solutions. Furthermore, many experiments require the control of other gases (such as oxygen or carbon dioxide) which requires constant perfusion. NEW METHOD: We describe a constant perfusion system that is air-tight (i.e., allows the accurate administration of hypoxic or hypercapnic gas mixtures), in which volatile anaesthetic is delivered via calibrated vaporisers by constant bubbling into the perfusing solution (and continuously monitored for stability by infrared spectroscopy in the headspace above the solution). RESULTS: We have confirmed the accuracy (i.e., linear relationship of dissolved concentrations with vapour dial settings) and stability (i.e., over time) of the anaesthetic concentrations in solutions in samples taken from the bottles into which anaesthetic is bubbled, and from samples taken from the tissue perfusion bath, using gas chromatrography-mass spectrometry (GC-MS). CONCLUSIONS: It is possible to deliver volatile anaesthetics in accurate concentrations to cell/tissue preparations whilst adjusting ambient air composition rapidly, stable over sustained time periods. PMID- 26554518 TI - Cell Population Data and reflex testing rules of cell analysis in pleural and ascitic fluids using body fluid mode on Sysmex XN-9000. AB - BACKGROUND: Although optical microscopy (OM) remains the reference technique for analysis of ascitic (AF) and pleural (PF) fluids, novel hematological analyzers are equipped with modules for body fluid (BF) analysis. This study was aimed to analyze the performance of XN-BF module in Sysmex XN-9000, and to develop validation rules for automated cell counts in BFs. METHODS: The evaluation of XN BF module included assessment of carryover, Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, data comparison with OM, and development of rules for assisting the validation of automated analysis of BFs and activating reflex testing. RESULTS: The carryover was negligible. The LoB, LoD, LoQ and linearity were always excellent. The comparison with OM was characterized by Pearson's correlations ranging from r=0.50 to r=0.99 (p<0.001), modest bias and high diagnostic concordance (Area Under the Curve between 0.85 and 0.99). The use of instrument-specific cut-offs further increased diagnostic concordance. The implementation of reflex testing rules based on XN-BF data increased sensitivity and specificity of BFs classification to 0.98 and 0.95. CONCLUSIONS: Our results suggest that the XN-BF module on Sysmex-9000 may be a suitable alternative to OM for screening BF samples, especially when specific validation rules are used. PMID- 26554519 TI - A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs. AB - BACKGROUND: Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the ChromoaTM CgA ELISA that did not display the apparent high dose hook effect. METHODS: Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. RESULTS: The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were <=4.6 and <=9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. CONCLUSIONS: The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. PMID- 26554520 TI - How to identify sulfamethoxazole crystals in the urine. PMID- 26554521 TI - Gastrointestinal toxicity of mycophenolate mofetil in rats: Effect of administration time. AB - This study investigates whether the intestinal toxicity of the immunosuppressive agent "mycophenolate mofetil (MMF)" varied according to the circadian dosing-time in rats. MMF (300 mg/kg) was acutely administered by i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). The results obtained showed that MMF-induced intestinal toxicity depends on circadian dosing-time in rats. A severe toxicity in the duodenum and jejunum was observed when the drug was administered at 7 HALO compared to controls and to other circadian times. This toxicity appeared in the form of villous and Liberkhun gland atrophy and nodular inflammation. At this dosing-time, MMF induced a significant increase of phosphatase alkaline activity and a significant decrease of gut mucosa weight, protein content and disaccharidases activities. Conversely, MMF dosing at 19 HALO induced lower gut toxicity, irrespective of type of toxicity explored. These data suggest the existence of a circadian rhythm of gut toxicity for this immunosuppressive agent and the best time of gastrointestinal tolerance (chronotolerance) of this agent was observed in the middle of the dark activity span of rats. PMID- 26554523 TI - Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methyl imidazolium tartrate on Scenedesmus obliquus. AB - Ionic liquids (ILs) are being used in various industries during the last few decades, while the good solubility and high stability of ILs may pose a potential threat to the aquatic environment. Effect of chiral ionic liquids (CILs) 1-alkyl 3-methyl imidazolium tartrate (RMIM T) on Scenedesmus obliquus (S.obliquus) was studied. The growth rate inhibition and cell membrane permeability increased with increasing RMIM T concentration and increasing alkyl chain lengths. The IC50 values of D-(-)-tartrate 1-hexyl-3-methyl imidazolium (D-(-)-HMIM T) were 28.30, 12.23,10.15 and 14.41 mg/L, respectively, at 24, 48, 72 and 96h. While that of L (+)-tartrate 1-hexyl-3-methyl imidazolium (L-(+)-HMIM T) were 15.97, 7.91, 9.43 and 12.04 mg/L respectively. The concentration of chl a, chl b and chl (a+b) decreased with increasing RMIM T concentration. The chlorophyll fluorescence parameters (F0, Fv/Fm, Fv/F0, Y(II), ETR and NPQ) were affected by RMIM T, indicating that the RMIM T will damage the PSII, inhibit the transmission of excitation energy, decrease the efficiency of photosynthesis. The results showed that there were enantioselective toxicity of RMIM T to algae, and the toxicity of L-(+)-RMIM T was greater than that of D-(-)-RMIM T, but the enantioselective difference becomes smaller with increasing exposure time, and with the increasing carbon chain length of cation, indicating that cation properties may have a larger effect on toxicity than anion properties. PMID- 26554524 TI - Antioxidative stress responses in the floating macrophyte Lemna minor L. with cylindrospermopsin exposure. AB - Cylindrospermopsin toxicity and oxidative stress have been examined in aquatic animals, however, only a few studies with aquatic plants have been conducted focusing on the potential for bioaccumulation of cylindrospermopsin. The oxidative stress effects caused by cylindrospermopsin on macrophytes have not yet been specifically studied. The oxidative stress response of Lemna minor L. with exposure to cylindrospermopsin, was therefore tested in this study. The hydrogen peroxide concentration together with the activities of the antioxidant enzymes (catalase, peroxidase, glutathione reductase and glutathione S-transferase) were determined after 24h (hours) of exposure to varying concentrations (0.025, 0.25, 2.5 and 25MUg/L) of cylindrospermopsin. Responses with longer exposure periods (48, 96, 168h) were tested only with exposure to 2.5 and 25MUg/L cylindrospermopsin. Additionally, the content of the carotenoids was determined as a possible non-enzymatic antioxidant defence mechanism against cylindrospermopsin. The levels of hydrogen peroxide increased after 24h even at the lowest cylindrospermopsin exposure concentrations. Catalase showed the most representative antioxidant response observed after 24h and maintained its activity throughout the experiment. Catalase activity corresponded with the contents of hydrogen peroxide at 2.5 and 25MUg/L cylindrospermopsin. The data suggest that glutathione S-transferase, glutathione reductase and the carotenoid content act together with catalase but are more sensitive to higher concentrations of cylindrospermopsin and after a longer exposure period (168h). The results indicate that cylindrospermopsin promotes oxidative stress in L. minor at concentrations of 2.5 and 25MUg/L. However, L. minor has sufficient defence mechanisms in place against this cyanobacterial toxin. Even though L. minor exhibits the potential to managing and control cylindrospermopsin contamination in aquatic systems, further studies in tolerance limits to cylindrospermopsin, uptake and experiments with prolonged exposure periods of more than 7 days are required. PMID- 26554522 TI - Chikungunya vaccines in development. AB - Chikungunya virus has become a global health threat, spreading to the industrial world of Europe and the Americas; no treatment or prophylactic vaccine is available. Since the late 1960s much effort has been put into the development of a vaccine, and several heterogeneous strategies have already been explored. Only two candidates have recently qualified to enter clinical phase II trials, a chikungunya virus-like particle-based vaccine and a recombinant live attenuated measles virus-vectored vaccine. This review focuses on the current status of vaccine development against chikungunya virus in humans and discusses the diversity of immunization strategies, results of recent human trials and promising vaccine candidates. PMID- 26554525 TI - Evaluation of predictor variables of diagnostic [18F] FDG-PET/CT in fever of unknown origin. AB - BACKGROUND: Fever of unknown origin (FUO) is defined as an illness having fever which lasts at least 3 weeks of duration and is higher than 38.3 oC on several measurements. The causes are infections, malignancies, noninfectious inflammatory diseases and miscellaneous. If [18F]FDG-PET/CT helps the final diagnosis, it is called contributory. The aim of the study is to evaluate the predictor variables effecting a contributory PET/CT for the diagnosis. METHODS: This is a retrospective cohort study conducted between June 2006 and May 2015 including 76 patients. The evaluated predictor variables are age, sex, ESR, CRP, fibrinogen, ferritin, albumin, haemoglobin level, platelet count, total leukocyte count, neutrophil percentage, lymphocyte percentage, ALP, LDH, ALAT, ASAT, GGT, total bilirubin, CK, RF, ANA, urinanalysis, chest radiography, abdominal US, lymphadenopathy, duration of fever, comorbid diseases and previous therapies. RESULTS: ESR (P=0.001), CRP (P=0.001), fibrinogen (P=0.009), lymphopenia (P<0.001), neutrophilia (P<0.001), ferritin (P<0.001), leukocytosis (P=0.003), duration of fever before PET/CT (<3 months) were found to be statistically significant for positive contribution of PET/CT results to the diagnosis. CONCLUSIONS: [18F]FDG-PET/CT is helpful and contributory for the diagnosis of FUO in patients having higher levels of CRP, ESR, ferritin, fibrinogen, leukocytosis, neutrophilia and shorter durations of fever (<3 months). PMID- 26554526 TI - Mechanisms of nitric oxide crosstalk with reactive oxygen species scavenging enzymes during abiotic stress tolerance in plants. AB - Nitric oxide (NO) acts in a concentration and redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging reactive oxygen species (ROS), such as superoxide anions (O(2)(-)*), to form peroxynitrite (ONOO(-)) or by acting as a signaling molecule, thereby altering gene expression. NO can interact with different metal centres in proteins, such as heme-iron, zinc-sulfur clusters, iron-sulfur clusters, and copper, resulting in the formation of a stable metal-nitrosyl complex or production of varied biochemical signals, which ultimately leads to modification of protein structure/function. The thiols (ferrous iron-thiol complex and nitrosothiols) are also involved in the metabolism and mobilization of NO. Thiols bind to NO and transport it to the site of action whereas nitrosothiols release NO after intercellular diffusion and uptake into the target cells. S nitrosoglutathione (GSNO) also has the ability to transnitrosylate proteins. It is an NO reservoir and a long-distance signaling molecule. Tyrosine nitration of proteins has been suggested as a biomarker of nitrosative stress as it can lead to either activation or inhibition of target proteins. The exact molecular mechanism(s) by which exogenous and endogenously generated NO (or reactive nitrogen species) modulate the induction of various genes affecting redox homeostasis, are being extensively investigated currently by various research groups. Present review provides an in-depth analysis of the mechanisms by which NO interacts with and modulates the activity of various ROS scavenging enzymes, particularly accompanying ROS generation in plants in response to varied abiotic stress. PMID- 26554527 TI - SGLT2 Inhibitors and Ketoacidosis: Cause for Concern? PMID- 26554528 TI - Effect of polyflux membranes on the improvement of hemodialysis-associated eosinophilia: a case series. AB - Hemodialysis-associated eosinophilia (HAE) is believed to be associated with allergic reactions to dialyzer materials. This study aimed to investigate the use of Polyflux membranes to improve HAE. Thirty-one patients suffering from HAE were included. Patients were dialyzed with polysulfone membranes when they developed HAE. After that, patients were dialyzed with Polyflux membranes three times every week, 4 h every time without changing the dialysis parameters and medication. Levels of peripheral eosinophils, hsCRP, IgE, C3a, IL-5 and peripheral CD4+ lymphocytes and CD8+ lymphocytes were assessed before Polyflux treatment, and at 4th, 8th and 12th weeks of treatment. Any symptoms including chest tightness and skin itching were observed during the study period. After 12 weeks of Polyflux membrane dialysis and compared with polysulfone membrane dialysis, levels of peripheral eosinophils were significantly decreased (1.26 +/- 0.61 vs. 0.71 +/- 0.29 * 10(9)/L, p < 0.001); serum IL-5 levels were significantly decreased (24.43 +/- 10.21 vs. 9.11 +/- 4.21 pg/mL, p < 0.001); and chest tightness and skin itching were significantly improved (45.2% vs. 19.4%, p = 0.028). After 12 weeks, there was no significant change in serum levels of hsCRP (2.00 +/- 0.94 vs. 1.81 +/- 0.79 mg/L, p = 0.352), IgE (104.61 +/- 98.79 vs. 114.95 +/- 101.07 IU/mL, p = 0.422) and C3a (121.61 +/- 34.04 vs. 120.29 +/- 32.81 ug/L, p = 0.316), and in peripheral levels of CD4+ (589 +/- 181 vs. 569 +/- 171 cells/mm(3), p = 0.672) and CD8+ (443 +/- 123 vs. 414 +/- 140 cells/mm(3), p = 0.395) cells. Eosinophil count was correlated with serum IL-5 levels (r = 0.873, p < 0.001). Changing to a Polyflux membrane may alleviate HAE and reduce serum IL-5 levels. Therefore, this could be a strategy to manage HAE in the clinical practice. PMID- 26554529 TI - Do Not Assume! PMID- 26554530 TI - microRNA expression changes after atrial fibrillation catheter ablation. AB - Atrial fibrillation (AF) is most common arrhythmia in general population, with increasing trend in mortality and morbidity. Electrophysiological and structural abnormalities, promoting abnormal impulse formation and propagation, lead to this disease. AF catheter ablation is related to a not small percentage of nonresponder patients. microRNAs (miRs) have been used as AF fibrotic and electrical alterations biomarkers. miRs may differentiate responders patients to ablative approach. Selective miR target therapy, as upregulation by adenovirus transfection and/or miR downregulation by antagomiR, may be used to treat AF patients. Catheter ablation of triggering electrical pulmonary veins activity or fibrotic areas defragmentation may be upgraded by miR therapy to prevent cardiac electrical and fibrotic remodeling after AF ablation. PMID- 26554531 TI - Post-transplant Merkel Cell Carcinoma. AB - Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC occurs more frequently than expected in immunosuppressed subjects, especially in organ transplant recipients. The current literature comprises reports of 79 organ transplant recipients with MCC. The risk of MCC in organ transplant recipients is increased up to 66-182-fold compared with the general population. In addition to the increased risk of developing MCC, immunosuppressed individuals have poorer MCC-specific survival. The aim of this review article is to familiarize organ transplant doctors with this unique and clinically challenging skin cancer, and to provide recent data on the diagnosis and current treatment recommendations for an immunosuppressed population. PMID- 26554532 TI - Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic-Cationic Drugs to the Brain. AB - Brain microdialysis is a powerful tool to estimate brain-to-plasma unbound concentration ratio at the steady state (Kp,uu) of compounds by direct measurement of the unbound concentration in brain interstitial fluid. Here, we evaluated a method to estimate Kp,uu values of multiple organic-cationic drugs simultaneously, by means of brain microdialysis combined with cocktail dosing. Five cationic drugs (diphenhydramine, memantine, oxycodone, pyrilamine, and tramadol), substrates of the proton-coupled organic cation antiport system, were selected as model drugs, and compared under single-dosing and cocktail-dosing conditions. We selected doses of the drugs at which no significant drug-drug interaction occurs at the proton-coupled organic cation antiport system in the blood-brain barrier (BBB). This was confirmed by uptake studies in hCMEC/D3 cells, an in vitro BBB model. The Kp,uu values after cocktail administration were in the range of 1.8-5.2, and were in good agreement with those after single administration. These results suggest that the microdialysis method with cocktail dosing is suitable to estimate Kp,uu values of several cationic drugs simultaneously, if there is no drug-drug interaction during BBB transport. The method could be useful for evaluating drug candidates with high Kp,uu values at an early stage in the development of central nervous system-acting drugs. PMID- 26554533 TI - Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model. AB - Currently, large-scale networks derived from dissociated neurons growing and developing in vitro on extracellular micro-transducer devices are the gold standard experimental model to study basic neurophysiological mechanisms involved in the formation and maintenance of neuronal cell assemblies. However, in vitro studies have been limited to the recording of the electrophysiological activity generated by bi-dimensional (2D) neural networks. Nonetheless, given the intricate relationship between structure and dynamics, a significant improvement is necessary to investigate the formation and the developing dynamics of three dimensional (3D) networks. In this work, a novel experimental platform in which 3D hippocampal or cortical networks are coupled to planar Micro-Electrode Arrays (MEAs) is presented. 3D networks are realized by seeding neurons in a scaffold constituted of glass microbeads (30-40 um in diameter) on which neurons are able to grow and form complex interconnected 3D assemblies. In this way, it is possible to design engineered 3D networks made up of 5-8 layers with an expected final cell density. The increasing complexity in the morphological organization of the 3D assembly induces an enhancement of the electrophysiological patterns displayed by this type of networks. Compared with the standard 2D networks, where highly stereotyped bursting activity emerges, the 3D structure alters the bursting activity in terms of duration and frequency, as well as it allows observation of more random spiking activity. In this sense, the developed 3D model more closely resembles in vivo neural networks. PMID- 26554534 TI - PRE- AND POSTNATAL MODIFICATIONS IN PARENTAL MENTAL REPRESENTATIONS IN THREE CASES OF FETAL GASTROSCHISIS DIAGNOSED DURING PREGNANCY. AB - The aim of this study was to identify possible effects of gastroschisis on parents' intrapsychic dynamics by applying an observational clinical approach. More specifically, we intend to (a) evaluate the representational style of parents informed about the diagnosis of fetal gastroschisis during pregnancy using the Interview of Maternal Representations During Pregnancy and the Interview of Paternal Representations During Pregnancy (M. Ammaniti, C. Candelori, M. Pola, & R. Tambelli, ) and (b) observe whether the baby's birth influences the parents' representational styles through the application of the same tools (the Interview of Maternal Representations After the Birth, M. Ammaniti & R. Tambelli, , and the Interview of Paternal Representations After the Birth, M. Ammaniti & R. Tambelli, ), adapted to the postnatal period. During the prenatal period, all parents showed a restricted/disinvested style. Three parents one mother and two fathers-changed their styles from restricted/disinvested to integrated between pregnancy and Month 6 after the birth of their child. Clinical data from the interviews and observations are discussed in an attempt at better defining intrapsychic dynamics of parents after a diagnosis of gastroschisis. PMID- 26554536 TI - Gold-Catalyzed Cyclization Processes: Pivotal Avenues for Organic Synthesis. AB - Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium-sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo-, regio-, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry. PMID- 26554535 TI - Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study. AB - OBJECTIVE: To examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant. METHODS: Data are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass index z-scores (BMI), waist circumference, and body fat at 8 years of age (n = 204) and BMI between 2-8 years of age (n = 285) according to PFAS concentrations. RESULTS: Children born to women in the top two PFOA terciles had greater adiposity at 8 years than children in the 1st tercile. For example, waist circumference (cm) was higher among children in the 2nd (4.3; 95% CI: 1.7, 6.9) and 3rd tercile (2.2; 95% CI: -0.5, 4.9) compared to children in the 1st tercile. Children in the top two PFOA terciles also had greater BMI gains from 2 to 8 years compared to children in the 1st tercile (P < 0.05). PFOS, PFNA, and PFHxS were not associated with adiposity. CONCLUSIONS: In this cohort, higher prenatal serum PFOA concentrations were associated with greater adiposity at 8 years and a more rapid increase in BMI between 2-8 years. PMID- 26554537 TI - Kinetic Resolution of Azomethine Imines by Bronsted Acid Catalyzed Enantioselective Reduction. AB - Azomethine imines are valuable substrates in asymmetric catalysis, and can be precursors to beta-amino carbonyl compounds and complex hydrazines. However, their utility is limited because complex and enantioenriched azomethine imines are often unavailable. Reported herein is a kinetic resolution of N,N'-cyclic azomethine imines by enantioselective reduction (s=13-43). This resolution was accomplished using a Bronsted acid catalyst, and represents the first example of the asymmetric reduction of azomethine imines. The pyrazolidinone product (up to 86 % ee) and the recovered azomethine imine (up to 99 % ee) can both be used to access the opposite enantiomers of valuable products. PMID- 26554538 TI - Successful Implantation from the Embryonic Aspect. AB - PROBLEM: Implantation failure is common in women with advanced maternal age, partly because of the increased number of aneuploid embryos. These women constitute the majority of patients for IVF treatment. As multiple pregnancies is a major hazard of preterm delivery, the aim is to select a competent embryo for single transfer. This study reviews currently used methods for selecting the competent embryo. METHOD OF THE STUDY: Literature search. RESULTS: The clinical value of currently used tests, for example pre-implantation genetic screening for aneuploidy, embryo morphology, morphokinetic measurements, extended culture to the blastocyst stage, as well as analysis of the follicular fluid and amino acid and glucose metabolism as well as oxygen consumption in embryo culture media, are discussed. CONCLUSION: Several approaches look promising, but the clinical value of these is yet to be confirmed in randomized clinical trials. Furthermore, some of the methods are too complicated for routine clinical application. PMID- 26554539 TI - Mechanochemical Synthesis and Antioxidant Activity of Curcumin-Templated Azoles. AB - A solvent-free, mechanochemical method for the synthesis of curcumin (1) derived 3,5-bis(styryl)pyrazoles and 3,5-bis(styryl)isoxazole (2a-g) at room temperature, with very short reaction time, is reported. Such earlier structural modifications of curcumin, at its beta-diketone unit by transforming it into an isosteric pyrazole or isoxazole unit, required prolonged heating. The evaluation of the antioxidant activity of these compounds, based on DPPH, FRAP, and beta-carotene bleaching assays, showed that several of these azoles are better antioxidants than curcumin, with the isoxazole derivative 2g being overall the best. Typically, the inhibition of 2,2-diphenyl-1-picrylhydrazyl (10(-2) mmol), expressed as EC50 values, by curcumin (1), 3,5-bis(4-hydroxy-3 methoxystyryl)pyrazole (2a), and 3,5-bis(4-hydroxy-3-methoxystyryl)isoxazole (2g) are 40 +/- 0.06, 14 +/- 0.18, and 8 +/- 0.11 MUmol, respectively. Moreover, the reported method is useful in accessing 3,5-bis(4-hydroxy-3-methoxystyryl)-1 phenylpyrazole (2b), which is important in studies related to neuroprotection and Alzheimer's disease, and 2a and 2g, which are inhibitors of protein kinases involved in neuronal excitotoxicity. PMID- 26554540 TI - Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue. AB - AIM: Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. MATERIAL AND METHODS: A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. RESULTS: Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). CONCLUSION: Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. PMID- 26554542 TI - The macrophage activation marker CD163 is associated with IL28B genotype and hepatic inflammation in chronic hepatitis C virus infected patients. AB - Recent data highlighted the association of the macrophage activation marker CD163 with histological inflammation and fibrosis in chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the influence of successful antiviral treatment and IL28B genotypes on macrophage activation reflected by CD163 levels in HCV infected patients. In a retrospective cohort study, serum sCD163 levels were correlated with results of liver histopathology, IL28B genotyping and clinical parameters in 329 patients with HCV infection, 15 healthy controls and in 161 patients who achieved a sustained virologic response after antiviral treatment. sCD163 levels were significantly higher in patients with chronic HCV infection in comparison to healthy controls (5202 vs 896 ng/mL, P < 0.001). In the multivariate logistic regression analyses, sCD163 was independently associated with histologically determined inflammation (P = 0.043) but not with fibrosis (P = 0.091). sCD163 dropped significantly after successful antiviral treatment in comparison to baseline values (5202 vs 3093 ng/mL, P < 0.001). In the univariate analyses, sCD163 was significantly associated with IL28B genotype (C/C vs C/T+T/T) with higher values in the C/C group (6098 vs 4812 ng/mL, P = 0.003). In the multivariate logistic regression model, sCD163 levels were significantly associated with IL28B genotype (P = 0.003) and sustained virologic response (SVR) (P < 0.001). Our data support the association of activated liver macrophages with hepatic necroinflammation in chronic HCV infection as sCD163 levels drop rapidly after SVR. The irresponsiveness of IL28B minor genotypes to interferon might be related to a lower level of macrophage activation in these patients. PMID- 26554541 TI - Production of RANKL by Memory B Cells: A Link Between B Cells and Bone Erosion in Rheumatoid Arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disease that often leads to joint damage. The mechanisms of bone damage in RA are complex, involving activation of bone-resorbing osteoclasts (OCs) by synoviocytes and Th17 cells. This study was undertaken to investigate whether B cells play a direct role in osteoclastogenesis through the production of RANKL, the essential cytokine for OC development. METHODS: RANKL production by total B cells or sorted B cell subpopulations in the peripheral blood and synovial tissue from healthy donors or anti-cyclic citrullinated peptide-positive patients with RA was examined by flow cytometry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. To define direct effects on osteoclastogenesis, B cells were cocultured with CD14+ monocytes, and OCs were enumerated by tartrate-resistant acid phosphatase staining. RESULTS: Healthy donor peripheral blood B cells were capable of expressing RANKL upon stimulation, with switched memory B cells (CD27+IgD-) having the highest propensity for RANKL production. Notably, switched memory B cells in the peripheral blood from RA patients expressed significantly more RANKL compared to healthy controls. In RA synovial fluid and tissue, memory B cells were enriched and spontaneously expressed RANKL, with some of these cells visualized adjacent to RANK+ OC precursors. Critically, B cells supported OC differentiation in vitro in a RANKL dependent manner, and the number of OCs was higher in cultures with RA B cells than in those derived from healthy controls. CONCLUSION: These findings reveal the critical importance of B cells in bone homeostasis and their likely contribution to joint destruction in RA. PMID- 26554543 TI - Compliance with Adult Congenital Heart Disease Guidelines: Are We Following the Recommendations? AB - OBJECTIVE: As the adult congenital heart disease population increases, poor transition from pediatric to adult care can lead to suboptimal quality of care and an increase in individual and institutional costs. In 2008, the American College of Cardiology and American Heart Association updated the adult congenital heart disease practice guidelines and in 2011, the American Heart Association recommended transition guidelines to standardize and encourage appropriate timing of transition to adult cardiac services. The objective of this study was to evaluate if patient age or complexity of congenital heart disease influences pediatric cardiologists' decision to transfer care to adult providers and to evaluate the compliance of different types of cardiology providers with current adult congenital heart disease treatment guidelines. DESIGN: A single-center retrospective review of 991 adult congenital heart disease patients identified by ICD-9 code from 2010 to 2012. SETTING: Academic and community outpatient cardiology clinics. PATIENTS: Nine hundred ninety-one patients who are 18 years and older with congenital heart disease. INTERVENTION: None. OUTCOMES MEASURES: The compliance with health maintenance and transfer of care recommendations in the outpatient setting. RESULTS: For patients seen by pediatric cardiologists, only 20% had transfer of care discussions documented, most often in younger simple patients. Significant differences in compliance with preventative health guidelines were found between cardiology provider types. CONCLUSION: Even though a significant number of adults with congenital heart disease are lost to appropriate follow-up in their third and fourth decades of life, pediatric cardiologists discussed transfer of care with moderate and complex congenital heart disease patients less frequently. Appropriate transfer of adults with congenital heart disease to an adult congenital cardiologist provides an opportunity to reinforce the importance of regular follow-up in adulthood and may improve outcomes as adult congenital cardiologists followed the adult congenital heart disease guidelines more consistently than pediatric or adult cardiologists. PMID- 26554544 TI - Copy-number variation of the filaggrin gene in Korean patients with atopic dermatitis: what really matters, 'number' or 'variation'? PMID- 26554546 TI - Threat of Secondary Chemical Contamination of Emergency Departments and Personnel: An Uncommon but Recurrent Problem. AB - OBJECTIVE: To analyze acute hazardous substance release surveillance data for events involving secondary contamination of hospital emergency departments (EDs). Secondary contamination of EDs may occur when a patient exposed to a hazardous chemical is not decontaminated before arrival at the ED and when ED staff are not wearing appropriate personal protective equipment. This can result in adverse health outcomes among department personnel, other patients, and visitors. Even events without actual secondary contamination risk can be real in their consequences and require the decontamination of the ED or its occupants, evacuation, or temporary shutdown of the ED. METHODS: Events involving secondary contamination were identified by using the Hazardous Substances Emergency Events Surveillance system and the National Toxic Substance Incidents Program from 2007 to 2013. RESULTS: Five incidents involving the threat of secondary contamination (0.02% of all events reported to the surveillance systems [n=33,001]) were detected and are described. Four incidents involved suspected secondary contamination in which the facility was evacuated or shut down. CONCLUSIONS: These results suggest that although rare, incidents involving secondary contamination continue to present a hazard for emergency departments. Suggested best practices to avoid secondary contamination have been described. Hospitals should be made aware of the risks associated with secondary contamination and the need to proactively train and equip staff to perform decontamination. PMID- 26554545 TI - Biodegradable-Polymer-Blend-Based Surgical Sealant with Body-Temperature-Mediated Adhesion. AB - The development of practical and efficient surgical sealants has the propensity to improve operational outcomes. A biodegradable polymer blend is fabricated as a nonwoven fiber mat in situ. After direct deposition onto the tissue of interest, the material transitions from a fiber mat to a film. This transition promotes polymer-substrate interfacial interactions leading to improved adhesion and surgical sealant performance. PMID- 26554547 TI - Vibrio cholerae O1 El Tor from southern Vietnam in 2010 was molecularly distinct from that present from 1999 to 2004. AB - The Vibrio cholerae O1 (VCO1) El Tor biotype appeared during the seventh cholera pandemic starting in 1961, and new variants of this biotype have been identified since the early 1990s. This pandemic has affected Vietnam, and a large outbreak was reported in southern Vietnam in 2010. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analyses (MLVA) were used to screen 34 VCO1 isolates from the southern Vietnam 2010 outbreak (23 patients, five contact persons, and six environmental isolates) to determine if it was genetically distinct from 18 isolates from outbreaks in southern Vietnam from 1999 to 2004, and two isolates from northern Vietnam (2008). Twenty-seven MLVA types and seven PFGE patterns were identified. Both analyses showed that the 2008 and 2010 isolates were distinctly clustered and separated from the 1999-2004 isolates. PMID- 26554551 TI - Effects of Menstrual Phase-Dependent Resistance Training Frequency on Muscular Hypertrophy and Strength. AB - The present study investigated how different training frequencies during menstrual phases affect muscle hypertrophy and strength. Fourteen eumenorrheic women performed 3 sets of arm curls (8-15 repetitions) until failure for 12 weeks. Depending on the menstrual cycle phase, each subject trained each arm separately after either a 3- or a 1-d.wk training protocol during the follicular phase (FP-T) and a 3- or 1-d.wk training protocol during the luteal phase (LP-T). Cross-sectional area (CSA), 1 repetition maximum, and maximum voluntary contraction significantly increased 6.2 +/- 4.4, 36.4 +/- 11.9, and 16.7 +/- 5.6%, respectively (p <= 0.05 vs. before training), in the FP-T group and 7.8 +/- 4.2, 31.8 +/- 14.1, and 14.9 +/- 12.7%, respectively (p <= 0.05 vs. before training), in the LP-T group. Changes in CSA between the FP-T and the LP-T groups significantly and positively correlated (r = 0.54, p <= 0.05). There were no major differences among the different training protocols with regard to muscle hypertrophy and strength. Therefore, we suggest that variations in female hormones induced by the menstrual cycle phases do not significantly contribute to muscle hypertrophy and strength gains during 12 weeks of resistance training. PMID- 26554552 TI - Determination of Anaerobic Threshold by Monitoring the O2 Pulse Changes in Endurance Cyclists. AB - The purpose of this study was to determine the validity of anaerobic threshold (AnT)-equivalent to the second turn point for lactate (LTP2)-estimation using the O2 pulse changes in highly trained endurance cyclists who do not show heart rate deflection point (HRDP) during incremental testing. Sixteen endurance cyclists (age, 24.8 +/- 4.7 years) and fifteen active men (age, 24.8 +/- 3.7 years) performed an incremental cycling test to exhaustion. Pulmonary oxygen uptake (V[Combining Dot Above]O2) and other hemodynamic variables, heart rate, and blood lactate concentration were measured continuously throughout the test. O2 pulse anaerobic threshold (O2 pulse-AnT) was defined as the second turn point in O2 pulse-workload curve. LTP2 was considered as gold standard assessment of AnT and was applied to confirm the validity of O2 pulse-AnT. Intraclass correlation coefficients and the Bland-Altman method were used to determine the relationship and agreement between the O2 corresponding to LTP2 and O2 pulse-AnT, respectively. The active men and 68.7% of the endurance cyclists showed HRDP, whereas all subjects showed O2 pulse-AnT during incremental testing. In both groups, the values for V[Combining Dot Above]O2 corresponding to LTP2 were not significantly different from the V[Combining Dot Above]O2 at O2 pulse-AnT. The V[Combining Dot Above]O2 at LTP2 and O2 pulse-AnT were highly correlated (endurance cyclists: R = 0.68; standard error of estimate [SEE] = 3.74 ml.kg.min and active men: R = 0.58; SEE = 2.91 ml.kg.min) and Bland-Altman plot revealed the limit of agreement of O2 at LTP2 and O2 pulse-AnT differences between 5.1 and 8.6 ml.kg.min (95% CI). In summary, results of this study showed that the second turn point in the O2 pulse-workload curve occurs around LTP2. Therefore, using O2 pulse-AnT is recommended for the noninvasive determination of AnT in highly trained endurance cyclists who do not show HRDP during incremental exercise. PMID- 26554553 TI - A Novel Technique for Experimental Flow Visualization of Mechanical Valves. AB - The geometry of the hinge region in mechanical heart valves has been postulated to play an important role in the development of thromboembolic events (TEs). This study describes a novel technique developed to visualize washout characteristics in mechanical valve hinge areas. A dairy-based colloidal suspension (DBCS) was used as a high-contrast tracer. It was introduced directly into the hinge containing sections of two commercially available valves mounted in laser-milled fluidic channels and subsequently washed out at several flow rates. Time-lapse images were analyzed to determine the average washout rate and generate intensity topography maps of the DBCS clearance. As flow increased, washout improved and clearance times were shorter in all cases. Significantly different washout rate time constants were observed between valves, average >40% faster clearance (p < 0.01). The topographic maps revealed that each valve had a characteristic pattern of washout. The technique proved reproducible with a maximum recorded standard error of mean (SEM) of +/-3.9. Although the experimental washout dynamics have yet to be correlated with in vivo visualization studies, the methodology may help identify key flow features influencing TEs. This visualization methodology can be a useful tool to help evaluate stagnation zones in new and existing heart valve hinge designs. PMID- 26554554 TI - A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations. AB - BACKGROUND: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. METHODS AND RESULTS: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. CONCLUSION: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals. PMID- 26554555 TI - Impact of a decision aid on reducing uncertainty: pilot study of women in their 40s and screening mammography. AB - BACKGROUND: In 2009 the United States Preventive Services Task Force updated its breast cancer screening guidelines to recommend that average-risk women obtain a screening mammogram every two years starting at age 50 instead of annually starting at age 40. Inconsistencies in data regarding the benefit versus risk of routine screening for women less than 50-years-of-age led to a second recommendation - that women in their forties engage in a shared decision making process with their provider to make an individualized choice about screening mammography that was right for them. In response, a web-based interactive mammography screening decision aid was developed and evaluated. METHODS: The decision aid was developed using an agile, iterative process. It was further honed based on feedback from clinical and technical subject matter experts. A convenience sample of 51 age- and risk-appropriate women was recruited to pilot the aid. Pre-post decisional conflict and screening choice was assessed. RESULTS: Women reported a significant reduction in overall decisional conflict after using the decision aid (Z = -5.3, p < 0.001). These participants also reported statistically significant reductions in each of the decisional conflict subscales: feeling uncertain (Z = -4.7, p < 0.001), feeling uninformed (Z = -5.2, p < 0.001), feeling unclear about values (Z = -5.0, p < 0.001), and feeling unsupported (Z = -4.0, p < 0.001). However, a woman's intention to obtain a screening mammogram in the next 1-2 years was not significantly changed (Wilcoxon signed-rank Z = -1.508, p = 0.132). CONCLUSION: This mammography screening decision aid brings value to patient care not by impacting what a woman chooses but by lending clarity to why or how she chooses it. PMID- 26554556 TI - Intestinal malrotation as a misdiagnosis of pediatric colchicine resistant familial Mediterranean fever. AB - BACKGROUND: Familial Mediterranean fever (FMF) is a disorder characterized by recurrent attacks of fever and serosal inflammation, particularly abdominal pain. Other disease processes, including medical and surgical emergencies, may mimic FMF, especially in atypical cases. CASE PRESENTATION: We present a case of an adolescent male, referred to us with a diagnosis of colchicine resistant FMF, ultimately diagnosed with intestinal malrotation and recurrent volvulus. CONCLUSIONS: In atypical presentations of FMF with potential "red flags", a thorough patient history is extremely important and should result in prompt referral for the appropriate diagnostic tests. PMID- 26554557 TI - Nano/micromotors for security/defense applications. A review. AB - The new capabilities of man-made micro/nanomotors open up considerable opportunities for diverse security and defense applications. This review highlights new micromotor-based strategies for enhanced security monitoring and detoxification of chemical and biological warfare agents (CBWA). The movement of receptor-functionalized nanomotors offers great potential for sensing and isolating target bio-threats from complex samples. New mobile reactive materials based on zeolite or activated carbon offer considerable promise for the accelerated removal of chemical warfare agents. A wide range of proof-of-concept motor-based approaches, including the detection and destruction of anthrax spores, 'on-off' nerve-agent detection or effective neutralization of chemical warfare agents have thus been demonstrated. The propulsion of micromotors and their corresponding bubble tails impart significant mixing that greatly accelerates such detoxification processes. These nanomotors will thus empower sensing and destruction where stirring large quantities of decontaminating reagents and controlled mechanical agitation are impossible or undesired. New technological breakthroughs and greater sophistication of micro/nanoscale machines will lead to rapid translation of the micromotor research activity into practical defense applications, addressing the escalating threat of CBWA. PMID- 26554559 TI - ICD-10: Our Newest Documentation Dilemma. PMID- 26554560 TI - Finding the Right Job: Two Key Issues. PMID- 26554558 TI - Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial. AB - BACKGROUND: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to L1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. METHODS/DESIGN: AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. DISCUSSION: The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. TRIAL REGISTRATION: The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014). PMID- 26554561 TI - ICD-10: Major Differences for Five Common Diagnoses. PMID- 26554562 TI - Addressing Ambulatory Patient Safety in Your Practice. PMID- 26554563 TI - Chronic Care Management in the Real World. PMID- 26554564 TI - Physician Burnout: Its Origin, Symptoms, and Five Main Causes. PMID- 26554571 TI - Staying Connected: Eight Tips for Mindful Office Visits With an EHR. PMID- 26554572 TI - Extending motifs in lithiocuprate chemistry: unexpected structural diversity in thiocyanate complexes. AB - The new area of lithio(thiocyanato)cuprates has been developed. Using inexpensive, stable and safe CuSCN for their preparation, these complexes revealed Lipshutz-type dimeric motifs with solvent-dependent point group identities; planar, boat-shaped and chair shaped conformers are seen in the solid state. In solution, both Lipshutz-type and Gilman structures are clearly seen. Since the advent in 2007 of directed ortho cupration, effort has gone into understanding the structure-reactivity effects of amide ligand variation in and alkali metal salt abstraction from Lipshutz-type cuprates such as (TMP)2Cu(CN)Li2(THF) 1 (TMP = 2,2,6,6-tetramethylpiperidide). The replacement of CN(-) with SCN(-) is investigated presently as a means of improving the safety of lithium cuprates. The synthesis and solid state structural characterization of reference cuprate (TMP)2Cu(CN)Li2(THP) 8 (THP = tetrahydropyran) precedes that of the thiocyanate series (TMP)2Cu(SCN)Li2(L) (L = OEt29, THF 10, THP 11). For each of 9-11, preformed TMPLi was combined with CuSCN (2 : 1) in the presence of sub stoichiometric Lewis base (0.5 eq. wrt Li). The avoidance of Lewis basic solvents incurs formation of the unsolvated Gilman cuprate (TMP)2CuLi 12, whilst multidimensional NMR spectroscopy has evidenced the abstraction of LiSCN from 9 11 in hydrocarbon solution and the in situ formation of Gilman reagents. The synthetic utility of 10 is established in the selective deprotometalation of chloropyridine substrates, including effecting transition metal-free homocoupling in 51-69% yield. PMID- 26554573 TI - Plant Esterase-Chitosan/Gold Nanoparticles-Graphene Nanosheet Composite-Based Biosensor for the Ultrasensitive Detection of Organophosphate Pesticides. AB - As broad-spectrum pesticides, organophosphates (OPs) are widely used in agriculture all over the world. However, due to their neurotoxicity in humans and their increasing occurrence in the environment, there is growing interest in their sensitive and selective detection. This paper reports a new cost-effective plant esterase-chitosan/gold nanoparticles-graphene nanosheet (PLaE-CS/AuNPs-GNs) biosensor for the sensitive detection of methyl parathion and malathion. Highly pure plant esterase is produced from plants at low cost and shares the same inhibition mechanism with OPs as acetylcholinesterase, and then it was used to prepare PLaE-CS/AuNPs-GNs nanocomposites, which were systematically characterized using SEM, TEM, and UV-vis. The PLaE-CS/AuNPs-GNs composite-based biosensor measured as low as 50 ppt (0.19 nM) of methyl parathion and 0.5 ppb (1.51 nM) of malathion (S/N = 3) with a calibration curve up to 200 ppb (760 nM) and 500 ppb (1513.5 nM) for methyl parathion and malathion, respectively. There is also no interference observed from most of common species such as metal ions, inorganic ions, glucose, and citric acid. In addition, its applicability to OPs contaminated real samples (carrot and apple) was also demonstrated with excellent response recovery. The developed simple, sensitive, and reliable PLaE-CS/AuNPs GNs composite-based biosensor holds great potential in OPs detection for food and environmental safety. PMID- 26554574 TI - Dealing with Ebola virus disease in Spain: epidemiological inquiries received by the Department of Public Health Alerts, April to December 2014. AB - We describe the inquiries regarding Ebola virus disease (EVD) received by the Department of Public Health Alerts of the Community of Madrid between April and December 2014. A total of 242 inquiries were received. Consultations were initiated most frequently by hospital clinicians (59 inquiries, 24%), private citizens (57 inquiries, 24%) and primary care physicians (53 inquiries, 22%). The most frequent topic of inquiry was possible EVD in a patient (215 inquiries, 89%). Among these, 31 persons (14%) presented both EVD-compatible symptoms and epidemiological risk factors, and 11 persons (5%) fulfilled the criteria for a person under investigation. Recent travel abroad was reported in 96 persons (45%), but only 32 (15%) had travelled to an EVD-affected area. Two high-risk and one low-risk contact were identified through these inquiries. Low specificity of the EVD symptoms led to many difficulties in protocol application. Ineffective communication with healthcare professionals and unfamiliarity with the EVD protocols caused many case classification errors. A rapid consultation service by telephone is essential for providing qualified advice during emergencies. Our experience may help other countries dimension their activities and resources for managing similar exceptional outbreaks in the future. PMID- 26554575 TI - Intramolecular C-C Bond Coupling of Nitriles to a Diimine Ligand in Group 7 Metal Tricarbonyl Complexes. AB - Dissolution of M(CO)3(Br)(L(Ar)) [L(Ar) = (2,6-Cl2-C6H3-NCMe)2CH2] in either acetonitrile [M = Mn, Re] or benzonitrile (M = Re) results in C-C coupling of the nitrile to the diimine ligand. When reacted with acetonitrile, the intermediate adduct [M(CO)3(NCCH3)(L(Ar))]Br forms and undergoes an intramolecular C-C coupling reaction between the nitrile carbon and the methylene carbon of the beta diimine ligand. PMID- 26554576 TI - Synthesis of Mn3O4/CeO2 Hybrid Nanotubes and Their Spontaneous Formation of a Paper-like, Free-Standing Membrane for the Removal of Arsenite from Water. AB - One-dimensional nanomaterials may organize into macrostructures to have hierarchically porous structures, which could not only be easily adopted into various water treatment apparatus to solve the separation issue of nanomaterials from water but also take full advantage of their nanosize effect for enhanced water treatment performance. In this work, a novel template-based process was developed to create Mn3O4/CeO2 hybrid nanotubes, in which a redox reaction happened between the OMS-2 nanowire template and Ce(NO3)3 to create hybrid nanotubes without the template removal process. Both the Ce/Mn ratio and the precipitation agent were found to be critical in the formation of Mn3O4/CeO2 hybrid nanotubes. Because of their relatively large specific surface area, porous structure, high pore volume, and proper surface properties, these Mn3O4/CeO2 hybrid nanotubes demonstrated good As(III) removal performances in water. These Mn3O4/CeO2 hybrid nanotubes could form paper-like, free-standing membranes spontaneously by a self-assembly process without high temperature treatment, which kept the preferable properties of Mn3O4/CeO2 hybrid nanotubes while avoiding the potential nanomaterial dispersion problem. Thus, they could be readily utilized in commonly used flow-through reactors for water treatment purposes. This approach could be further applied to other material systems to create various hybrid nanotubes for a broad range of technical applications. PMID- 26554577 TI - Ultrafast Time-Resolved Spectroscopy of Diarylethene-Based Photoswitchable Deoxyuridine Nucleosides. AB - Photoswitches based on the diarylethene architecture have been attracting considerable attention for the investigation and control of a variety of biological processes. The reversible photoisomerization reaction between their open- and closed-ring forms can be selectively addressed by irradiation with light of two markedly different wavelengths. In this work, the dynamics of the photochromic ring-opening reaction of four novel diarylethene-based photoswitchable deoxyuridine nucleosides is investigated by femtosecond transient absorption. Upon photoexcitation with sub-20 fs pulses in the first absorption band (500 nm), all four photoswitches showed a fast ballistic excited-state deactivation within less than 500 fs toward the S1/S0 conical intersection. Transient data was globally analyzed, and a relaxation kinetic model with a branching between open and closed ring forms without any loss channels was derived. Ring-opening quantum yields, Phir-o, were found to strongly depend on the substituents (R), ranging from 0.64 (dU(PSI): R = 2-naphthyl) to 0.30 (dU(PSIV): R = 2-pyridyl). PMID- 26554578 TI - DermaComp: A Pharmaceutical Compounding iPhone((r)) Application for Dermatologists Designing Personalized Topical Medications. PMID- 26554579 TI - Skin Flaps for the Repair of Multiple Adjacent Tumors. AB - In daily clinical practice, the dermatologic surgeon frequently has to excise closely adjacent tumors in the facial region. In such cases, planning of an appropriate reconstruction technique is essential. The aim is to treat all of the lesions in a single surgical intervention, if possible, and to achieve a good functional and cosmetic outcome. We present 5 patients in whom a single flap was used to repair multiple adjacent defects. PMID- 26554580 TI - Guidelines for Classification of Acute Kidney Diseases and Disorders. AB - Recent efforts have standardized definitions and classification systems for acute kidney injury (AKI) and chronic kidney disease (CKD). These efforts have enhanced communication, recognition, and awareness of acute and CKDs and stimulated research on both disorders. However, abnormalities of kidney function and structure can occur that do not meet the current criteria for either disorder. Recognizing the need for a uniform approach encompassing both acute and chronic abnormalities of kidney function and structure, the Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline for AKI Guidelines proposed an operational definition for acute kidney diseases and disorders (AKD) that encompasses both AKI and any newly recognized kidney disease that does not meet the current definitions for AKI or CKD. Recent commentaries have highlighted that it may be premature to adopt these criteria into clinical practice, but that they may be useful for application in epidemiologic studies. Future research is needed to better understand the clinical characteristics, incidence, and prognosis of AKD, as well as the implications of case identification based on the AKD criteria. PMID- 26554581 TI - Fast Stiffness Mapping of Cells Using High-Bandwidth Atomic Force Microscopy. AB - The cytoskeleton controls cellular morphology and mediates the mechanical interactions between a cell and its environment. Atomic force microscopy (AFM) has the unique capability to map cytoskeletal mechanics and structures with nanometer resolution. However, whole-cell cytomechanical imaging with conventional AFM techniques is limited by low imaging speed. Here, we present fast nanomechanical mapping of cells using high-bandwidth AFM (HB-AFM), where >10(6) nanoindentation measurements were acquired in ~10 min-a task that would take weeks to finish using conventional AFM. High-bandwidth measurements enabled capture of the entire tip-sample interaction for each tap on cells, engendering a new measurement ("force phase") that exceeds the contrast of conventional tapping mode and enabling spectral visualization of >10 harmonics. The abundance of measurements allowed discovery of subtle cytomechanical features, including the stiffness of fibers of the cellular spectrin network in situ. This approach bridges HB-AFM and high-harmonic imaging and opens future opportunities for measuring the dynamic mechanical properties of living cells. PMID- 26554582 TI - Transcriptome Analysis of Blunt Snout Bream (Megalobrama amblycephala) Reveals Putative Differential Expression Genes Related to Growth and Hypoxia. AB - The blunt snout bream (Megalobrama amblycephala) is an important freshwater aquaculture species, but it is sensitive to hypoxia. No transcriptome data related to growth and hypoxia response are available for this species. In this study, we performed de novo transcriptome sequencing for the liver and gills of the fast-growth family and slow-growth family derived from 'Pujiang No.1' F10 blunt snout bream that were under hypoxic stress and normoxia, respectively. The fish were divided into the following 4 groups: fast-growth family under hypoxic stress, FH; slow-growth family under hypoxic stress, SH; fast-growth family under normoxia, FN; and slow-growth family under normoxia, SN. A total of 185 million high-quality reads were obtained from the normalized cDNA of the pooled samples, which were assembled into 465,582 contigs and 237,172 transcripts. A total of 31,338 transcripts from the same locus (unigenes) were annotated and assigned to 104 functional groups, and 23,103 unigenes were classified into seven main categories, including 45 secondary KEGG pathways. A total of 22,255 (71%) known putative unigenes were found to be shared across the genomes of five model fish species and mammals, and a substantial number (9.4%) of potentially novel genes were identified. When 6,639 unigenes were used in the analysis of differential expression (DE) genes, the number of putative DE genes related to growth pathways in FH, SH, SN and FN was 159, 118, 92 and 65 in both the liver and gills, respectively, and the number of DE genes related to hypoxic response was 57, 33, 23 and 21 in FH, FN, SH and SN, respectively. Our results suggest that growth performance of the fast-growth family should be due to complex mutual gene regulatory mechanisms of these putative DE genes between growth and hypoxia. PMID- 26554583 TI - In Vivo Real-Time Control of Gene Expression: A Comparative Analysis of Feedback Control Strategies in Yeast. AB - Real-time automatic regulation of gene expression is a key technology for synthetic biology enabling, for example, synthetic circuit's components to operate in an optimal range. Computer-guided control of gene expression from a variety of inducible promoters has been only recently successfully demonstrated. Here we compared, in silico and in vivo, three different control algorithms: the Proportional-Integral (PI) and Model Predictive Control (MPC) controllers, which have already been used to control gene expression, and the Zero Average Dynamics (ZAD), a control technique used to regulate electrical power systems. We chose as an experimental testbed the most commonly used inducible promoter in yeast: the galactose-responsive GAL1 promoter. We set two control tasks: either force cells to express a desired constant fluorescence level of a reporter protein downstream of the GAL1 promoter (set-point) or a time-varying fluorescence (tracking). Using a microfluidics-based experimental platform, in which either glucose or galactose can be provided to the cells, we demonstrated that both the MPC and ZAD control strategies can successfully regulate gene expression from the GAL1 promoter in living cells for thousands of minutes. The MPC controller can track fast reference signals better than ZAD but with a higher actuation effort due to the large number of input switches it requires. Conversely, the PI controller's performance is comparable to that achieved by the MPC and the ZAD controllers only for the set-point regulation. PMID- 26554584 TI - An Ovol2-Zeb1 Mutual Inhibitory Circuit Governs Bidirectional and Multi-step Transition between Epithelial and Mesenchymal States. AB - Reversible epithelial-to-mesenchymal transition (EMT) is central to tissue development, epithelial stemness, and cancer metastasis. While many regulatory elements have been identified to induce EMT, the complex process underlying such cellular plasticity remains poorly understood. Utilizing a systems biology approach integrating modeling and experiments, we found multiple intermediate states contributing to EMT and that the robustness of the transitions is modulated by transcriptional factor Ovol2. In particular, we obtained evidence for a mutual inhibition relationship between Ovol2 and EMT inducer Zeb1, and observed that adding this regulation generates a novel four-state system consisting of two distinct intermediate phenotypes that differ in differentiation propensities and are favored in different environmental conditions. We identified epithelial cells that naturally exist in an intermediate state with bidirectional differentiation potential, and found the balance between EMT-promoting and inhibiting factors to be critical in achieving and selecting between intermediate states. Our analysis suggests a new design principle in controlling cellular plasticity through multiple intermediate cell fates and underscores the critical involvement of Ovol2 and its associated molecular regulations. PMID- 26554585 TI - A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1. AB - BACKGROUND: Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown. RESULTS: Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-kB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time. CONCLUSIONS: Expression of a rev1-vpu fusion gene does not affect regular Rev and Vpu functions or alter HIV-1 replication in primary target cells. Since there is no evidence for increased replication fitness of rev1-vpu encoding viruses, this polymorphism likely emerged in the context of other mutations within and/or outside the rev1-vpu intergenic region, and may have a neutral phenotype. PMID- 26554586 TI - Partner Notification for Reduction of HIV-1 Transmission and Related Costs among Men Who Have Sex with Men: A Mathematical Modeling Study. AB - BACKGROUND: Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch men-who-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. METHODS: Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a 20 year period. RESULTS: Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in the short term, with increasing cost-effectiveness over time: from ?41,476 -?41, 736 (IQR ?40,529-?42,147; ?40,791-?42,397) to ?5,773 -?5,887 (?5,134-?7,196; ?5,411 ?6,552) per QALY gained over a 5 and 20 year period, respectively. The full monetary benefits of partner notification by preventing new HIV infections become more apparent over time. CONCLUSIONS: Partner notification will not lead to the end of the HIV epidemic, but will prevent new infections and be increasingly cost effectiveness over time. PMID- 26554587 TI - Host Genetics and Environment Drive Divergent Responses of Two Resource Sharing Gall-Formers on Norway Spruce: A Common Garden Analysis. AB - A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp.) that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L.) support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch). Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members respond to host genetics supports our hypothesis that the canopies of Norway spruce differ in their community phenotypes. PMID- 26554588 TI - More Delusions May Be Observed in Low-Proficient Multilingual Alzheimer's Disease Patients. AB - BACKGROUND: Language impairment and behavioral symptoms are both common phenomena in dementia patients. In this study, we investigated the behavioral symptoms in dementia patients with different language backgrounds. Through this, we aimed to propose a possible connection between language and delusion. METHODS: We recruited 21 patients with Alzheimer's disease (AD), according to the DSM-IV and NINCDS-ADRDA criteria, from the memory clinic of the Cardinal Tien Hospital in Taipei, Taiwan. They were classified into two groups: 11 multilinguals who could speak Japanese, Taiwanese and Mandarin Chinese, and 10 bilinguals who only spoke Taiwanese and Mandarin Chinese. There were no differences between age, education, disease duration, disease severity, environment and medical care between these two groups. Comprehensive neuropsychological examinations, including Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), Verbal fluency, Chinese version of the Boston naming test (BNT) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), were administered. RESULTS: The multilingual group showed worse results on the Boston naming test. Other neuropsychological tests, including the MMSE, CASI and Verbal fluency, were not significantly different. More delusions were noted in the multilingual group. Three pairs of subjects were identified for further examination of their differences. These three cases presented the typical scenario of how language misunderstanding may cause delusions in multilingual dementia patients. Consequently, more emotion and distorted ideas may be induced in the multilinguals compared with the MMSE-matched controls. CONCLUSION: Inappropriate mixing of language or conflict between cognition and emotion may cause more delusions in these multilingual patients. This reminds us that delusion is not a pure biological outcome of brain degeneration. Although the cognitive performance was not significantly different between our groups, language may still affect their delusion. PMID- 26554589 TI - Neural Mechanisms of Cortical Motion Computation Based on a Neuromorphic Sensory System. AB - The visual cortex analyzes motion information along hierarchically arranged visual areas that interact through bidirectional interconnections. This work suggests a bio-inspired visual model focusing on the interactions of the cortical areas in which a new mechanism of feedforward and feedback processing are introduced. The model uses a neuromorphic vision sensor (silicon retina) that simulates the spike-generation functionality of the biological retina. Our model takes into account two main model visual areas, namely V1 and MT, with different feature selectivities. The initial motion is estimated in model area V1 using spatiotemporal filters to locally detect the direction of motion. Here, we adapt the filtering scheme originally suggested by Adelson and Bergen to make it consistent with the spike representation of the DVS. The responses of area V1 are weighted and pooled by area MT cells which are selective to different velocities, i.e. direction and speed. Such feature selectivity is here derived from compositions of activities in the spatio-temporal domain and integrating over larger space-time regions (receptive fields). In order to account for the bidirectional coupling of cortical areas we match properties of the feature selectivity in both areas for feedback processing. For such linkage we integrate the responses over different speeds along a particular preferred direction. Normalization of activities is carried out over the spatial as well as the feature domains to balance the activities of individual neurons in model areas V1 and MT. Our model was tested using different stimuli that moved in different directions. The results reveal that the error margin between the estimated motion and synthetic ground truth is decreased in area MT comparing with the initial estimation of area V1. In addition, the modulated V1 cell activations shows an enhancement of the initial motion estimation that is steered by feedback signals from MT cells. PMID- 26554590 TI - An Element of Determinism in a Stochastic Flagellar Motor Switch. AB - Marine bacterium Vibrio alginolyticus uses a single polar flagellum to navigate in an aqueous environment. Similar to Escherichia coli cells, the polar flagellar motor has two states; when the motor is counter-clockwise, the cell swims forward and when the motor is clockwise, the cell swims backward. V. alginolyticus also incorporates a direction randomization step at the start of the forward swimming interval by flicking its flagellum. To gain an understanding on how the polar flagellar motor switch is regulated, distributions of the forward Deltaf and backward Deltab intervals are investigated herein. We found that the steady-state probability density functions, P(Deltaf) and P(Deltab), of freely swimming bacteria are strongly peaked at a finite time, suggesting that the motor switch is not Poissonian. The short-time inhibition is sufficiently strong and long lasting, i.e., several hundred milliseconds for both intervals, which is readily observed and characterized. Treating motor reversal dynamics as a first-passage problem, which results from conformation fluctuations of the motor switch, we calculated P(Deltaf) and P(Deltab) and found good agreement with the measurements. PMID- 26554591 TI - Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice. AB - Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (DeltaPsim) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches. PMID- 26554592 TI - Spatial Representations in Local Field Potential Activity of Primate Anterior Intraparietal Cortex (AIP). AB - The execution of reach-to-grasp movements in order to interact with our environment is an important subset of the human movement repertoire. To coordinate such goal-directed movements, information about the relative spatial position of target and effector (in this case the hand) has to be continuously integrated and processed. Recently, we reported the existence of spatial representations in spiking-activity of the cortical fronto-parietal grasp network (Lehmann & Scherberger 2013), and in particular in the anterior intraparietal cortex (AIP). To further investigate the nature of these spatial representations, we explored in two rhesus monkeys (Macaca mulatta) how different frequency bands of the local field potential (LFP) in AIP are modulated by grip type, target position, and gaze position, during the planning and execution of reach-to-grasp movements. We systematically varied grasp type, spatial target, and gaze position and found that both spatial and grasp information were encoded in a variety of frequency bands (1-13Hz, 13-30Hz, 30-60Hz, and 60-100Hz, respectively). Whereas the representation of grasp type strongly increased towards and during movement execution, spatial information was represented throughout the task. Both spatial and grasp type representations could be readily decoded from all frequency bands. The fact that grasp type and spatial (reach) information was found not only in spiking activity, but also in various LFP frequency bands of AIP, might significantly contribute to the development of LFP-based neural interfaces for the control of upper limb prostheses. PMID- 26554593 TI - Clinicopathologic features and prognostic implications of Gankyrin protein expression in non-small cell lung cancer. AB - PURPOSE: The expression of Gankyrin, a liver cancer-related oncoprotein, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of Gankyrin expression in NSCLC remains unclear. METHODS: Gankyrin expression was assessed using immunohistochemical (IHC) methods in 166 paired paraffin-embedded NSCLC specimens and adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT PCR) and Western blotting were employed to measure the expression of Gankyrin in 24 paired fresh NSCLC specimens and the corresponding normal tissues. The association of Gankyrin expression with clinicopathological parameters was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Gankyrin expression on survival. RESULTS: Data showed that Gankyrin was expressed in 78.3% (130/166) and 28.9% (48/166) of cancer lesions and corresponding adjacent normal tissue, respectively. And the Gankyrin overexpression in tumor tissue occurred in 53.6% (89/166) of patients, while overexpression of Gankyrin in normal tissue occurred only in 4.8% (8/166) of patients (P<0.001). Semi-quantitative RT-PCR and Western blotting showed that NSCLC specimens had increased Gankyrin mRNA and protein expression compared to the corresponding normal tissues. Out of all the clinicopathological factors analyzed, Gankyrin overexpression was significantly correlated with lymphatic metastasis (P<0.001) and p-TNM stage (P<0.001). Gankyrin-overexpressed NSCLC patients had a significantly shorter survival time (P<0.001, Log-rank test), and the prognostic significance of Gankyrin overexpression was apparent in both squamous cell carcinoma patients (P=0.028) and adenocarcinoma patients (P<0.001). Multivariate analysis indicated that Gankyrin overexpression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.51; P=0.041). CONCLUSION: Our results indicate that Gankyrin overexpression is of clinical significance and can serve as a prognostic biomarker in NSCLC. PMID- 26554595 TI - Contracting C2C12 myotubes release CCL2 in an NF-kappaB-dependent manner to induce monocyte chemoattraction. AB - Muscle inflammation following exercise is characterized by expression of inflammatory cytokines and chemokines. Exercise also increases muscle macrophages derived from circulating monocytes. However, it is unknown whether muscle cells themselves attract circulating monocytes, or what is the underlying mechanism. We used an in vitro system of electrical stimulation (ES) causing C2C12 myotube contraction to explore whether monocyte chemoattraction ensues and investigated the mediating chemoattractants. Conditioned medium from ES-contracted myotubes caused robust chemoattraction of THP-1 monocytes across Boyden chambers. Following ES, expression of several known monocyte chemokines [C-C motif ligand 2 (CCL2) and C-X-C motif ligand (CXCL)1, -2, and -5] was elevated, but of these, only recombinant CCL2 effectively reproduced monocyte migration. Electrically stimulated myotubes secreted CCL2, and neutralization of CCL2 in conditioned medium or antagonizing the CCL2 receptor (CCR2) in THP-1 monocytes inhibited ES induced monocyte migration. N-benzyl-p-toluene sulfonamide (BTS), a myosin II ATPase inhibitor, prevented ES-induced myotube contraction but not CCL2 gene expression and secretion. The membrane-permeant calcium chelator BAPTA-AM reduced ES-induced CCL2 secretion. Hence, electrical depolarization, rather than mechanical contraction, drives the rise in CCL2, with partial calcium input. ES activated the NF-kappaB pathway; NF-kappaB inhibitors reduced ES-induced CCL2 gene expression and secretion and repressed ES-induced THP-1 chemoattraction. Thus, electrically stimulated myotubes chemoattract monocytes through NF-kappaB regulated CCL2 secretion. PMID- 26554594 TI - The MAFB transcription factor impacts islet alpha-cell function in rodents and represents a unique signature of primate islet beta-cells. AB - Analysis of MafB(-/-) mice has suggested that the MAFB transcription factor was essential to islet alpha- and beta-cell formation during development, although the postnatal physiological impact could not be studied here because these mutants died due to problems in neural development. Pancreas-wide mutant mice were generated to compare the postnatal significance of MafB (MafB(Deltapanc)) and MafA/B (MafAB(Deltapanc)) with deficiencies associated with the related beta cell-enriched MafA mutant (MafA(Deltapanc)). Insulin(+) cell production and beta cell activity were merely delayed in MafB(Deltapanc) islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafB(Deltapanc) mice, which is supported by the death of MafAB(Deltapanc) mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafB(Deltapanc) islet alpha-cells. Based upon these results, we conclude that MafB is only essential to islet alpha-cell activity and not beta-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet beta-cells. Here, we show that nonhuman primate (NHP) islet alpha- and beta-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet beta-cell. PMID- 26554596 TI - The role of eye movements in the size-speed illusion of approaching trains. AB - Recent research on the perceived speed of large moving objects, compared to smaller moving objects, has revealed the presence of a size-speed illusion. This illusion, where a large object seems to be moving more slowly than a small object travelling at the same speed may account for collisions between motor cars and trains at level crossings, which is a serious safety issue in New Zealand and worldwide. One possible reason for the perceived size-speed difference may be related to the movement of our eyes when we track moving vehicles. In order to investigate this, we tested observers' relative speed perception of moving objects (both abstract and more detailed objects) moving in depth towards the observer, presented on a computer display and eye movements recorded with an eyetracker. Experiment 1 confirmed first the size-speed illusion when the observers were situated further away (18, 36m) from the simulated rail crossing or intersection. It also revealed that the eye movement behaviour of our participants was different when they judged the speeds of the small and large objects; eye fixations were localised around the visual centroid of longer objects and hence were further from the front of the moving large objects than the smaller ones. Experiment 2 found that manipulating eye movements could reduce the magnitude of the illusion. When observers tracked targets (dots) that were placed at corresponding locations at the front of the small object and the long object respectively, they perceived the speeds of the two objects as equal. When target dots were placed closer to the visual centroid, observers perceived the larger object to be moving slower. These results demonstrate that there is a close relationship between eye movement behaviour and our perceived judgement of an approaching train's speed. PMID- 26554597 TI - Noise exposure assessment among groundskeepers in a university setting: A pilot study. AB - Approximately 870,000 U.S. workers are employed as landscaping and groundskeeping workers who perform various tasks and use a variety of tools that expose them to high noise levels, increasing their risk to noise-induced hearing loss (NIHL). Several studies on noise exposure and NIHL in other job sectors have been published, but those on groundskeepers are very limited. This study aims to characterize the noise exposure of groundskeepers. Participants were monitored over their entire work shift for personal noise exposure by wearing noise dosimeters at shoulder level, 4 in from the ear. Using two different dosimeter settings (OSHA and NIOSH), the time-weighted averages (TWAs) and 1-min averages of noise exposure levels in decibels (dBA) were obtained. The participants were also asked to fill out an activity card daily to document their tasks, tools used, location and noise perception. Sound pressure levels (SPLs) produced by various groundskeeping equipment and tools were measured at full throttle near the ear of the operator using a sound level meter. These measurements were used to assess worker noise exposure profiles, particularly the contributing source of noise. The overall mean OSHA and NIOSH TWA noise exposures were 82.2+/-9.2 (range of 50.9-100 dBA) and 87.8+/-6.6 dBA (range of 67.2-102.9 dBA), respectively. Approximately 46% of the OSHA TWAs exceeded the OSHA action limit of 85 dBA. About 76% of the NIOSH TWAs exceeded 85 dBA, and 42% exceeded 90 dBA. The SPLs of equipment and tools measured ranged from 75- 106 dBA, most of which were at above 85 dBA and within the 90-100 dBA range. Hand-held power tools and ride-on equipment without enclosed cab may have contributed significantly to worker noise exposure. This study demonstrates that groundskeepers may be routinely exposed to noise levels above the OSHA and NIOSH exposure limits, and that the implementation of effective hearing conservation programs is necessary to reduce their risk to NIHL. PMID- 26554598 TI - Different in vitro exposure regimens of murine primary macrophages to silver nanoparticles induce different fates of nanoparticles and different toxicological and functional consequences. AB - Silver nanoparticles (Ag-NPs) are used in a variety of consumers' goods. Their toxicological impact is currently intensely studied, mostly upon acute exposure, but their intracellular dissolution and fate is rather poorly documented. In this study, murine primary macrophages were exposed to a single high but non-lethal dose of Ag-NPs or to repeated, low doses of Ag-NPs. Cells were either collected immediately after acute exposure or after 72 h of recovery in the NP-free exposure medium. Ag intracellular content and distribution were analyzed by particle-induced X-ray emission, transmission electron microscopy coupled to energy-dispersive spectroscopy analysis and inductively coupled plasma mass spectrometry. In parallel, macrophage functionality as well as inflammatory and thiol-responses were assessed after Ag-NP exposure. We show that Ag accumulation in macrophages is similar upon acute and repeated exposure to Ag-NPs, and that Ag is partly expelled from cells during the 72 h recovery stage. However, acute exposure leads to a strong response of macrophages, characterized by reduced mitochondrial membrane potential, phagocytic capacity and nitric oxide (NO) production upon lipopolysaccharide (LPS) stimulation. Under this condition, we also show an increased release of proinflammatory cytokines as well as a decreased release of anti-inflammatory cytokines. This response is reversible since these biomarkers reach their basal level after the recovery phase; and is much less intense in repeatedly exposed cells. These results suggest that repeated exposure of macrophages to Ag-NPs, which is a more realistic exposure scenario than acute exposure, leads to significant Ag intracellular accumulation but a much less intense toxicological response. PMID- 26554599 TI - Endometrioma With Ovarian Calcification. PMID- 26554600 TI - Erratum to: Methods for characterization of organic compounds in atmospheric aerosol particles. PMID- 26554601 TI - Potential of gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry for screening and quantification of hexabromocyclododecane. AB - A fast method for the screening and quantification of hexabromocyclododecane (sum of all isomers) by gas chromatography using a triple quadrupole mass spectrometer with atmospheric pressure chemical ionization (GC-APCI-QqQ) is proposed. This novel procedure makes use of the soft atmospheric pressure chemical ionization source, which results in less fragmentation of the analyte than by conventional electron impact (EI) and chemical ionization (CI) sources, favoring the formation of the [M - Br](+) ion and, thus, enhancing sensitivity and selectivity. Detection was based on the consecutive loses of HBr from the [M - Br](+) ion to form the specific [M - H5Br6](+) and [M - H4Br5](+) ions, which were selected as quantitation (Q) and qualification (q) transitions, respectively. Parameters affecting ionization and MS/MS detection were studied. Method performance was also evaluated; calibration curves were found linear from 1 pg/MUL to 100 pg/MUL for the total HBCD concentration; instrumental detection limit was estimated to be 0.10 pg/MUL; repeatability and reproducibility, expressed as relative standard deviation, were better than 7% in both cases. The application to different real samples [polyurethane foam disks (PUFs), food, and marine samples] pointed out a rapid way to identify and allow quantification of this compound together with a number of polybrominated diphenyl ethers (BDE congeners 28, 47, 66, 85, 99, 100, 153, 154, 183, 184, 191, 196, 197, and 209) and two other novel brominated flame retardants [i.e., decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6 tribromophenoxy)ethane (BTBPE)] because of their presence in the same fraction when performing the usual sample treatment. PMID- 26554602 TI - The prevalence of primary headache disorders in Nepal: a nationwide population based study. AB - BACKGROUND: Headache disorders are among the most prevalent and burdensome global public-health problems. Within countries, health policy depends upon knowledge of health within the local populations, but the South-East Asia Region (SEAR), among WHO's six world regions, is the only one for which no national headache prevalence data are available. METHODS: In a cross-sectional population-based study, adults representative of the Nepali-speaking population aged 18-65 years and living in Nepal were randomly recruited using stratified multistage cluster sampling. They were visited unannounced at home by trained interviewers who used a culturally-adapted Nepali translation of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire. RESULTS: There were 2,100 participants (1,239 females [59.0 %], 861 males [41.0 %]; mean age 36.4 +/- 12.8 years) with 9 refusals (participation rate 99.6 %). Over half (1,100; 52.4 %) were resident above 1,000 m and almost one quarter (470; 22.4 %) lived at or above 2,000 m. The 1-year prevalence of any headache was 85.4 +/- 1.5 % (gender- and age-adjusted 84.9 %), of migraine 34.7 +/- 2.0 % (34.1 %), of tension-type headache (TTH) 41.1 +/- 2.1 % (41.5 %), of headache on >=15 days/month 7.7 +/- 1.1 % (7.4 %) and of probable medication overuse headache (pMOH) 2.2 +/- 0.63 % (2.1 %). There was a strong association between migraine and living at altitude >=1,000 m (AOR = 1.6 [95 % CI: 1.3-2.0]; p < 0.001). There was a less strong association between TTH and urban dwelling (AOR = 1.3 [95 % CI: 1.1-1.6]; p = 0.003), and a possibly artefactual negative association between TTH and living above 1,000 m (AOR = 0.7 [95 % CI: 0.6-0.8]; p < 0.001). CONCLUSION: Headache disorders are very common in Nepal. Migraine is unusually so, and strongly associated with living at altitude, which in very large part accounts for the high national prevalence: the age- and gender- standardised prevalence in the low-lying Terai is 27.9 %. Headache occurring on >=15 days/month is also common. This new evidence will inform national health policy and provide a basis for health-care needs assessment. However, research is needed to explain the association between migraine and altitude, since it may be relevant to health-care interventions. PMID- 26554605 TI - Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis. AB - Inflammatory Bowel Disease (IBD) is a multifactorial disorder involving dysregulation of the immune response and bacterial translocation through the intestinal mucosal barrier. Previously, we have shown that activation of the bile acid sensor Farnesoid X Receptor (FXR), which belongs to the family of nuclear receptors, improves experimental intestinal inflammation, decreasing expression of pro-inflammatory cytokines and protecting the intestinal barrier. Here, we aimed to investigate the immunological mechanisms that ameliorate colitis when FXR is activated. We analyzed by FACS immune cell populations in mesenteric lymph nodes (MLN) and in the spleen to understand whether FXR activation alters the systemic immune response. We show that FXR activation by obeticholic acid (OCA) has systemic anti-inflammatory effects that include increased levels of plasma IL 10, inhibition of both DSS-colitis associated decrease in splenic dendritic cells (DCs) and increase in Tregs. Impact of OCA on DC relative abundance was seen in spleen but not MLN, possibly related to the increased FXR expression in splenic DCs compared to MLN DCs. Moreover, FXR activation modulates the chemotactic environment in the colonic site of inflammation, as Madcam1 expression is decreased, while Ccl25 is upregulated. Together, our data suggest that OCA treatment elicits an anti-inflammatory immune status including retention of DCs in the spleen, which is associated with decreased colonic inflammation. Pharmacological FXR activation is therefore an attractive new drug target for treatment of IBD. PMID- 26554604 TI - Dietary and donepezil modulation of mTOR signaling and neuroinflammation in the brain. AB - Recent clinical and laboratory evidences suggest that high fat diet (HFD) induced obesity and its associated metabolic syndrome conditions promotes neuropathology in aging and age-related neurological disorders. However, the effects of high fat diet on brain pathology are poorly understood, and the effective strategies to overcome these effects remain elusive. In the current study, we examined the effects of HFD on brain pathology and further evaluated whether donepezil, an AChE inhibitor with neuroprotective functions, could suppress the ongoing HFD induced pathological changes in the brain. Our data demonstrates that HFD induced obesity results in increased neuroinflammation and increased AChE activity in the brain when compared with the mice fed on low fat diet (LFD). HFD administration to mice activated mTOR pathway resulting in increased phosphorylation of mTOR(ser2448), AKT(thr308) and S6K proteins involved in the signaling. Interestingly, donepezil administration with HFD suppressed HFD induced increases in AChE activity, and partially reversed HFD effects on microglial reactivity and the levels of mTOR signaling proteins in the brain when compared to the mice on LFD alone. However, gross levels of synaptic proteins were not altered in the brain tissues of mice fed either diet with or without donepezil. In conclusion, these results present a new insight into the detrimental effects of HFD on brain via microglial activation and involvement of mTOR pathway, and further demonstrates the possible therapeutic role for donepezil in ameliorating the early effects of HFD that could help preserve the brain function in metabolic syndrome conditions. PMID- 26554606 TI - Ichthyobacterium seriolicida gen. nov., sp. nov., a member of the phylum 'Bacteroidetes', isolated from yellowtail fish (Seriola quinqueradiata) affected by bacterial haemolytic jaundice, and proposal of a new family, Ichthyobacteriaceae fam. nov. AB - A novel Gram-stain-negative, rod-shaped (0.3 * 4-6 MUm), non-flagellated, aerobic strain with gliding motility, designated JBKA-6T, was isolated in 1991 from a yellowtail fish, Seriola quinqueradiata, showing symptoms of bacterial haemolytic jaundice. 16S rRNA gene sequence analysis showed that strain JBKA-6T was related most closely to members of the family Flavobacteriaceae in the phylum 'Bacteroidetes'. Furthermore, based on gyrB gene sequence analysis, JBKA-6T was classified into a single clade within the order Flavobacteriales, which was distinct from the known clades of the families Flavobacteriaceae, Blattabacteriaceae and Cryomorphaceae. The predominant isoprenoid quinone was identified as MK-6 (97.9 %), and the major cellular fatty acids (>10 %) were C14 : 0 and iso-C15 : 0. The main polar lipids were phosphatidylethanolamine, three unidentified phospholipids, two unidentified aminophospholipids and two unidentified polar lipids. The DNA G+C content of JBKA-6T, as derived from its whole genome, was 33.4 mol%. The distinct phylogenetic position and phenotypic traits of strain JBKA-6T distinguish it from all other described species of the phylum 'Bacteroidetes', and therefore it was concluded that strain JBKA-6T represents a new member of the phylum 'Bacteroidetes', and the name Ichthyobacterium seriolicida gen. nov., sp. nov. is proposed. The type strain of Ichthyobacterium seriolicida is JBKA-6T ( = ATCC BAA-2465T = JCM 18228T). We also propose that Icthyobacterium gen. nov. is the type genus of a novel family, Ichthyobacteriaceae fam. nov. PMID- 26554607 TI - An effective utilization management strategy by dual approach of influencing physician ordering and gate keeping. AB - OBJECTIVES: There is increasing recognition of the importance of appropriate laboratory test utilization. We investigate the effect of a multifaceted educational approach that includes physician feedback on individual test ordering, in conjunction with targeted restriction, on the utilization of selected laboratory tests. DESIGN AND METHODS: Scientific evidence was compiled on the usefulness and limitations of tests suspected of being over utilized in our laboratories. A variety of approaches were used to deliver education on each of the targeted tests, with greater focus on primary care physicians (PCPs). Feedback on requesting behavior of these tests was also communicated to the latter group which included an educational component. Laboratory based restriction of testing was also exercised, including the unbundling of our electrolyte panel. RESULTS: PCP requesting patterns for the selected tests were found to be markedly skewed. The interventions implemented over the study period resulted in a substantial 51% reduction in overall ordering of five of the targeted tests equating to an annual marginal cost saving of $60,124. Unbundling of the electrolyte panel resulted in marginal cost savings that equated annually to $42,500 on chloride and $48,000 on total CO2. CONCLUSIONS: A multifaceted educational approach combined with feedback on utilization and laboratory driven gate-keeping significantly reduced the number of laboratory tests suspected of being redundant or unjustifiably requested. Laboratory professionals are well positioned to manage demand on laboratory tests by utilizing evidence base in developing specific test ordering directives and gate-keeping rules. PMID- 26554608 TI - T cell polarizing properties of probiotic bacteria. AB - Different commensal bacteria employed as probiotics have been shown to be endowed with immunomodulatory properties and to actively interact with antigen presenting cells, such as dendritic cells and macrophages. In particular, different strains of probiotic bacteria may induce the secretion of a discrete cytokine profile able to induce divergent T cell polarization. Here, we briefly review current knowledge regarding the effects of different species and strains of probiotic bacteria on T cell polarization. Given that the loss of intestinal homeostasis is frequently associated with an aberrant T cell polarization profile, a comprehensive knowledge of the immunomodulatory potential of these bacteria is crucial for their employment in the management of human immune-mediated pathologies, such as allergies or inflammatory bowel diseases. PMID- 26554609 TI - MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population. AB - Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population. PMID- 26554611 TI - Evaluation of Changes in Human Corneas After Femtosecond Laser-Assisted LASIK and Small-Incision Lenticule Extraction (SMILE) Using Non-Contact Tonometry and Ultra High-Speed Camera (Corvis ST). AB - PURPOSE: To evaluate theoretical biomechanical advantages of human corneas treated with small incision lenticule extraction (SMILE) compared with femtosecond laser-assisted LASIK (FS-LASIK) Patients and methods: In a prospective, comparative, non-randomized, consecutive case series patients with moderate to high myopia and/or astigmatism underwent corneal refractive surgery. Patients either received standard FS-LASIK or SMILE. Preoperatively and up to 3 months postoperatively data were analyzed including tomography with Pentacam HR, Goldmann tonometry, non-contact tonometry, and deformability of the cornea using an ultra-high-speed camera (Corvis ST). Data were analyzed and p < 0.05 was considered as statistically significant (t-test). RESULTS: Seventy-three patients (128 eyes) were treated. Forty-eight eyes of 29 patients underwent FS-LASIK and 80 eyes of 44 patients underwent SMILE. Preoperative spherical equivalent (SE) was -3.23 +/- 1.64 D (FS-LASIK group) and -4.83 +/- 1.63 D (SMILE group) (p < 0.0001). Almost all parameters obtained by Corvis ST between preoperative and postoperative measurements showed significant changes after refractive surgery. Significant changes were seen between both groups postoperatively. However, matched pair subgroup analysis (n = 69; 26 eyes FS-LASIK; 43 eyes SMILE) of eyes with initially equal pachymetry, intraocular pressure, SE, and difference of pre- to postoperative pachymetry (p>0.05), showed no significant changes in parameters measured with Corvis ST (p>0.05). CONCLUSIONS: Corneal biomechanical parameters measured preoperatively with Corvis ST showed significant differences postoperatively in total and in both groups. In subgroup analysis with homogenous groups, FS-LASIK showed no significant changes in biomechanical data measured with Corvis ST compared with SMILE. PMID- 26554610 TI - Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies. AB - Replication errors are the main cause of mitochondrial DNA (mtDNA) mutations and a compelling approach to decrease mutation levels would therefore be to increase the fidelity of the catalytic subunit (POLgammaA) of the mtDNA polymerase. Here we genomically engineer the tamas locus, encoding fly POLgammaA, and introduce alleles expressing exonuclease- (exo(-)) and polymerase-deficient (pol(-)) POLgammaA versions. The exo(-) mutant leads to accumulation of point mutations and linear deletions of mtDNA, whereas pol(-) mutants cause mtDNA depletion. The mutant tamas alleles are developmentally lethal but can complement each other in trans resulting in viable flies with clonally expanded mtDNA mutations. Reconstitution of human mtDNA replication in vitro confirms that replication is a highly dynamic process where POLgammaA goes on and off the template to allow complementation during proofreading and elongation. The created fly models are valuable tools to study germ line transmission of mtDNA and the pathophysiology of POLgammaA mutation disease. PMID- 26554612 TI - Understanding the role of the news media in HPV vaccine uptake in the United States: Synthesis and commentary. AB - Vaccination rates for the human papillomavirus (HPV) vaccine fall below targets and only 2 states and the District of Columbia require the vaccine for middle school-age children. Messages conveyed through news media-to parents, providers, policymakers, and the general public-may contribute to sluggish vaccination rates and policy action. In this commentary, we review the findings from 13 published studies of news media coverage of the HPV vaccine in the United States since FDA licensure in 2006. We find 2 important themes in news coverage: a rising focus on political controversy and a consistent emphasis on the vaccine as for girls, even beyond the point when the vaccine was recommended for boys. These political and gendered messages have consequences for public understanding of the vaccine. Future research should continue to monitor news media depictions of the HPV vaccine to assess whether political controversy will remain a pronounced theme of coverage or whether the media ultimately depict the vaccine as a routine public health service. PMID- 26554613 TI - Ultrasound evaluation of the stomach and gastric emptying in pregnant women at term: a case-control study. AB - BACKGROUND: This study aims to assess the rate of gastric emptying in pregnant women in the third trimester scheduled for elective caesarean section (CS), in view to highlight the aspiration risk. METHODS: A prospective case-control study, with the approval of the Ethics Committee, was performed. At term pregnant women (group A) scheduled for CS and volunteer controls were recruited (group B). The ultrasonographic measurement of the antral area was performed, after a standardized meal, with a Convex probe. The antrum was displayed in the sagittal or parasagittal projections in the right upper quadrant, medial to the mid clavicular line. The diameters of the antrum were measured and then the antral area was calculated. The measurements were conducted at 10 (T1), 90 (T2) and 240 (T3) minutes from the meal. Anthropometric data were collected for each patient. RESULTS: In group B, antrum distention was observed already after 10 minutes from the meal, and then a gradual decrease in the antral area until 4 hours after the meal was registered. On the contrary, in group A (at term pregnant) there was an initial smaller increase of antral area, followed by a greater increase that lasts up to 90 minutes, and finally a delayed and smaller reduction. CONCLUSIONS: In pregnant women at term, the stomach does not seem to be able to expand immediately after the meal. The transit of food is completed later than in not pregnant women. The ultrasound of the stomach allows identifying delays gastric emptying and highlighting patients at risk of aspiration. PMID- 26554614 TI - Closed-loop anesthesia. AB - Automated anesthesia which may offer to the physician time to control hemodynamic and to supervise neurological outcome and which may offer to the patient safety and quality was until recently consider as a holy grail. But this field of research is now increasing in every component of general anesthesia (hypnosis, nociception, neuromuscular blockade) and literature describes some successful algorithms - single or multi closed-loop controller. The aim of these devices is to control a predefined target and to continuously titrate anesthetics whatever the patients' co morbidities and surgical events to reach this target. Literature contains many randomized trials comparing manual and automated anesthesia and shows feasibility and safety of this system. Automation could quickly concern other aspects of anesthesia as fluid management and this review proposes an overview of closed-loop systems in anesthesia. PMID- 26554615 TI - Pathophysiological role of cytoglobin, the fourth globin in mammals, in liver diseases. AB - Cytoglobin (Cygb), a stellate cell-specific globin, has recently drawn attention due to its association with liver fibrosis and cancer. In human and rodent livers, Cygb is expressed only in stellate cells and can be utilized as a marker to distinguish stellate cells from hepatic fibroblast-derived myofibroblasts. Loss of Cygb accelerates liver fibrosis and cancer development despite its etiology in mouse models of chronic liver injury. This review discusses the current perception of the distribution, regulation and function of Cygb with regard to liver diseases, with an emphasis on its role in tumorigenesis. Further investigation of Cygb may shed new light on the biology of organ carcinogenesis. PMID- 26554616 TI - Retrospective Analysis of Protein- and Carbohydrate-Focused Diets Combined with Exercise on Metabolic Syndrome Prevalence in Overweight and Obese Women. AB - BACKGROUND: To examine the effect of protein-focused (PRO, 1.14 g/kg/day) and carbohydrate-focused (CHO, ~2.2 g/kg/day) diets (~1600 kcals) combined with 10 weeks of circuit exercise training in sedentary overweight/obese women (N = 661, age 46 +/- 11 years) on metabolic syndrome (MetS). METHODS: We retrospectively analyzed eight exercise training studies performed from 2002-2014. Primary (MetS), secondary (MetS z-scores and individual MetS components), and tertiary outcomes [body mass index (BMI) by WHO cut points] were analyzed using chi square, GLM, and McNemar's tests. RESULTS: Both groups experienced significant weight loss, improvements in fitness, and reductions in MetS prevalence from baseline to follow-up (PRO: 49% to 42%, CHO: 42% to 36%, both P < 0.01). MetS z score improvement (~66.5%) was similar for both groups with no significant between-group differences noted. There were also no significant differences for individual component features between groups for the following: waist circumference (-0.28 +/- 0.02 vs. -0.28 +/- 0.025 cm, P = 0.97), glucose (-0.07 +/- 0.03 vs. -0.08 +/- 0.04 mM, P = 0.87), triglycerides (-0.16 +/- 0.04 vs. 0.09 +/- 0.04 mM, P = 0.20), high-density lipoprotein cholesterol (-0.21 +/- 0.03 vs. -0.19 +/- 0.04 mM, P = 0.68), and systolic BP (-0.16 +/- 0.4 vs. -0.24 +/- 0.05 mmHg, P = 0.26). Diastolic BP showed a minor advantage for the PRO group ( 0.14 +/- 0.05 vs. -0.30 +/- 0.05 mmHg P = 0.02). When stratified by BMI, those with morbid obesity did not show a significant improvement in MetS while following a PRO-focused diet; however, caution is warranted given the exploratory nature of this analysis. CONCLUSIONS: Our findings suggest that a low-moderate calorie diet partitioned for CHO and PRO preference is equally effective when combined with a structured exercise program for reducing the prevalence of MetS prevalence in overweight/obese women. PMID- 26554617 TI - In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy. AB - OBJECTIVE: Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy. MATERIALS AND METHODS: Biopsies were taken from antrum and fundus of 112 adult and 3 children with Urea Breath Test positive with dyspeptic symptoms and analyzed for H. pylori culture and antibacterial activity. Antimicrobial susceptibility tests were performed for clarithromycin, metronidazole, levofloxacin, moxifloxacin, ciprofloxacin, tetracycline, amoxicillin, ampicillin, and rifabutin by a modified agar dilution susceptibility test. RESULTS: Bacterial culture was successful in 100 out of 115 patients. Helicobacter pylori strains were isolated from 98 antrum and 83 fundus samples. The rate of recovery of H. pylori strains was 90.50% (181/200). The percentages of resistance were as follows: clarithromycin 72.44% antrum, 72.28% fundus; metronidazole 34.69% antrum, 42.16% fundus; levofloxacin 42.85% antrum, 53.01% fundus; moxifloxacin 37.35% antrum, 46.57% fundus; ciprofloxacin 39.47% antrum, 44.28% fundus; tetracycline 2.63% antrum, 2.85% fundus; amoxicillin 1.02% antrum, 1.20% fundus; ampicillin 0% antrum and fundus and rifabutin 0% antrum, 1.20% fundus. A total of 35 subjects harbored multi-resistant strains. CONCLUSIONS: This study underlines the high rate of resistance to clarithromycin, metronidazole and quinolones, which may reflect an overuse of them. Culture and susceptibility test, should be performed to prevent the emergence of multi resistance and to assess an efficacious regimen. PMID- 26554618 TI - Histologic prognostic markers in stage IIA colorectal cancer: a comparative study. AB - OBJECTIVE: pTNM stage IIA colorectal cancer (CRC) is not currently submitted to any adjuvant treatment due to its good prognosis. Nevertheless, a percentage of cases unexpectedly recur. The aim of this study was to assess and compare the prognostic value and inter-observer agreement of a novel histological grading system based on the counting of poorly differentiated clusters (PDC) of cancer cells and that of conventional histological grade, lymphatic, venous and perineural invasion (LVI, VI, PNI), tumour budding (TB) and tumor border configuration in stage IIA CRC. MATERIALS AND METHODS: the afore mentioned histological parameters were assessed in 82 stage IIA CRCs. Inter-observer agreement and correlation with tumour relapse were analyzed by using Fleiss Cohen's weighted K statistics, Fisher exact test and Chi-squared test. The Mantel Cox log-rank test was applied to assess the strength of association with disease free interval (DFI). RESULTS: inter-observer agreement was very good/good in the assessment of PDC presence and grade, while it was moderate at best in the evaluation of the other parameters. The presence of PDC, high PDC grade, LVI and TB were significantly associated with disease progression (p < 0.0001; p = 0.0012; p = 0.0308; p = 0.0002) and shorter DFI (p = 0.0001; p < 0.0001; p = 0.0129; p = 0.0008). PDC presence (p < 0.0001) and TB (p = 0.012) were independent prognostic factors in multivariate analysis. CONCLUSIONS: our findings suggest that the assessment of PDC may be useful to stratify patients with stage IIA CRC for recurrence risk, and to identify high risk patients who could benefit from adjuvant chemotherapy. PMID- 26554619 TI - The role of routinely given hyoscine-N-butylbromide in colonoscopy: a double blind, randomized, placebo-controlled, clinical trial. AB - OBJECTIVE: Hyoscine-N-butylbromide (HBB) has been proposed to ease colonoscopy and improve mucosal visualization, yet the results from previous studies are conflicting. In our prospective, double-blind, placebo-controlled, randomized study we aimed at evaluating whether routine administration of HBB, before and during colonoscopy, ease the procedure or increase the detection rate for polyps. MATERIAL AND METHODS: One hundred fifty outpatients scheduled for an elective colonoscopy were randomized to receive intravenous injections of either 10 mg hyoscine-N-butylbromide or saline before insertion and at cecum. Patient tolerance and technical ease of colonoscopy were evaluated by visual analogue scale (VAS). Procedure times were recorded. Number of detected polyps per patient was evaluated as well. Heart rate was monitored with a pulse oximetry. RESULTS: HBB did not improve patient tolerance or technically ease the procedure as evaluated by VAS. However, HBB led to faster ileal intubation (1.5 vs 2.0 min, p < 0.001) and shorter total procedure time (22.0 vs 24.0 min, p = 0.03). Patients who received HBB also needed less often external abdominal pressure (48.6 vs 66.7%, p = 0.03). HBB did not improve polyp detection rate (0.89 vs 0.91, p = 0.90). HBB induced a significant rise in heart rate (p < 0.001) and more often tachycardia (17.6 vs 0%, p < 0.001). CONCLUSIONS: Routine administration of HBB before and during colonoscopy yields only limited improvement in the technical performance of the examination compromised by high incidence of tachycardia. PMID- 26554620 TI - An emerging issue in differential diagnosis of diarrhea: sprue-like enteropathy associated with olmesartan. PMID- 26554621 TI - Delayed neuroprotection against cerebral ischemia reperfusion injury: putative role of BDNF and GSK-3beta. AB - AIM: Numerous studies have demonstrated the possible neuroprotective role of lithium treatment against neurological disorders. However, the role of lithium in delayed phase of neuronal death against focal ischemia has not been explored. Therefore, the present study was designed to investigate the effect and molecular mechanisms of post-lithium treatment against cerebral ischemic reperfusion (I/R) injury and associated cognitive deficits in rats. METHODS: I/R injury was induced by right middle cerebral artery occlusion and lithium (40 and 60 mg/kg) were given intraperitoneally, 24 h after the insult and continued for 1 week with 24-h interval. Using Lasser Doppler, cerebral blood flow was monitored before, during and after MCAO induction. Besides behavioral, biochemical, and histological evaluation, levels of tumor necrosis factor alpha (TNF-alpha) and brain-derived neurotrophic factor (BDNF) were also estimated. RESULTS: I/R injury resulted in significant elevation of neurological deficits, oxidative stress, neuroinflammation, and cognitive impairments. We found that lithium injection, 24 h after I/R-injury continued for 1 week, dose dependently prevented behavioral abnormality and cognitive impairments. Moreover, lithium attenuated the levels of oxidative stress and pro-inflammatory-cytokines TNF-alpha level. Further, lithium treatments significantly reduced neuronal damage and augmented healthy neuronal count and improved neuronal density in hippocampus. These neuroprotective effects of delayed lithium treatment were associated with upregulation of neurotrophic factor BDNF levels. CONCLUSION: Delayed lithium treatment provides neuroprotection against cerebral I/R injury and associated cognitive deficits by upregulating BDNF expression that opens a new avenue to treat I/R injury even after active cell death. PMID- 26554622 TI - An effective analytic method for detecting tissue-specific genes in RNA-seq experiments. AB - AIM: To develop an analytic method for identifying tissue-specific (TS) genes from RNA-seq data. MATERIALS & METHODS: Based on a negative binomial distribution, we develop a statistical method containing consecutive procedures incorporating data variability from replicates in each tissue. RESULTS: Simulations show that our approach can effectively identify at least 94% of the truly TS genes if the sample size is 3 and at least 84% of the TS genes detected by our method are truly TS genes. We illustrated the utility of our method in an in-house RNA-seq project and produced sensible results. CONCLUSION: Our approach not only directly works on discrete data but also naturally incorporates data variability. It works effectively for detecting TS genes. PMID- 26554623 TI - Things I Wish I Knew about Nursing Homes Before Working There. PMID- 26554624 TI - A Case of Miliary Tuberculosis Presenting with Whitlow of the Thumb. PMID- 26554625 TI - EDITOR'S STATEMENT. PMID- 26554626 TI - Effect of Subchronic Intravenous Morphine Infusion and Naloxone-Precipitated Morphine Withdrawal on P-gp and Bcrp at the Rat Blood-Brain Barrier. AB - Chronic morphine regimen increases P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) expressions at the rat blood-brain barrier (BBB) but what drives this effect is poorly understood. The objective of this study is to assess subchronic continuous morphine infusion and naloxone-precipitated morphine withdrawal effects on P-gp/Bcrp contents and activities at the rat BBB. Rats were treated either with (i) a continuous i.v. morphine for 120 h, (ii) escalating morphine dosing (10-40 mg/kg, i.p., 5 days), (iii) a chronic morphine regimen (10 mg/kg s.c., 5 days) followed by a withdrawal period (2 days) and treatment for 3 additional days. Animal behavior was assessed after naloxone-precipitated withdrawal (1 mg/kg, s.c.). P-gp/Bcrp expressions and activities were determined in brain microvessels by qRT-PCR, Western blot, UHPLC-MS/MS, and in situ brain perfusion of P-gp or Bcrp substrates. Results show continuous i.v. morphine did not change P-gp/Bcrp protein levels in rat brain microvessels, whereas naloxone precipitated withdrawal after escalating or chronic morphine dose regimen increased Mdr1a and Bcrp mRNA levels by 1.4-fold and 2.4-fold, respectively. Conversely, P-gp/Bcrp protein expressions remained unchanged after naloxone administration, and brain uptake of [3H]-verapamil (P-gp) and [3H]-mitoxantrone (Bcrp) was not altered. The study concludes subchronic morphine infusion and naloxone-precipitated morphine withdrawal have poor effect on P-gp/Bcrp levels at the rat BBB. PMID- 26554628 TI - Boundary Disturbances Revisited: An Application With an Apperception Test. AB - A Rorschach study of boundary disturbance and thought disorder by Blatt and Ritzler ( 1974 ) was replicated using the newly developed Picture Projection Test (PPT), a modern alternative to the Thematic Apperception Test (TAT). Twenty-five individuals with pathological Rorschach records were compared to 25 individuals with nonpathological Rorschachs. A coding system for the PPT was devised using concepts from the Blatt and Ritzler study and Rorschach thought disorder variables from the Comprehensive System (Exner, 2003 ). The pathological group showed significantly more boundary disturbance on the PPT. Only one Contamination (the most severe manifestation of boundary disturbance and thought disorder) appeared in the pathological group. The nonpathological group had no Contamination responses. It is recommended that future researchers repeat the study with a psychotic group compared to a nonpsychotic group. PMID- 26554627 TI - A Screenable In Vivo Assay for Mitochondrial Modulators Using Transgenic Bioluminescent Caenorhabditis elegans. AB - The multicellular model organism Caenorhabditis elegans is a small nematode of approximately 1 mm in size in adulthood that is genetically and experimentally tractable. It is economical and easy to culture and dispense in liquid medium which makes it well suited for medium-throughput screening. We have previously validated the use of transgenic luciferase expressing C. elegans strains to provide rapid in vivo assessment of the nematode's ATP levels.(1-3) Here we present the required materials and procedure to carry out bioassays with the bioluminescent C. elegans strains PE254 or PE255 (or any of their derivative strains). The protocol allows for in vivo detection of sublethal effects of drugs that may identify mitochondrial toxicity, as well as for in vivo detection of potential beneficial drug effects. Representative results are provided for the chemicals paraquat, rotenone, oxaloacetate and for four firefly luciferase inhibitory compounds. The methodology can be scaled up to provide a platform for screening drug libraries for compounds capable of modulating mitochondrial function. Pre-clinical evaluation of drug toxicity is often carried out on immortalized cancerous human cell lines which derive ATP mostly from glycolysis and are often tolerant of mitochondrial toxicants.(4,5) In contrast, C. elegans depends on oxidative phosphorylation to sustain development into adulthood, drawing a parallel with humans and providing a unique opportunity for compound evaluation in the physiological context of a whole live multicellular organism. PMID- 26554629 TI - Race- and Sex-Specific Incidence Rates and Predictors of Total Knee Arthroplasty: Seven-Year Data From the Osteoarthritis Initiative. AB - OBJECTIVE: To determine race- and sex-specific rates of total knee arthroplasty (TKA) and to document independent effects of demographic factors on TKA incidence in a population with radiographically confirmed osteoarthritis (OA). METHODS: We used data from the Osteoarthritis Initiative, a US-based, multicenter longitudinal study of knee OA. We selected subjects with radiographic symptomatic OA at baseline and determined TKA incidence rates (ratio of TKAs to time at risk for TKA) over 84 months of followup. We used multivariable Poisson regression to identify independent associations between demographic factors and TKA utilization. RESULTS: During the study period there were 223 TKAs among 1,915 subjects for an incidence of 1.9% (95% confidence interval [95% CI] 1.7-2.2%). The overall rate was 1.9% (95% CI 1.5-2.3%) in men versus 2.0% (95% CI 1.7-2.3%) in women, and 2.2% (95% CI 1.9-2.6%) in whites versus 1.0% (95% CI 0.7-1.5%) in nonwhites. We observed a statistically significant interaction between sex and age (stratified at <65 and >=65 years at end of followup), wherein male sex was associated with decreased risk of TKA for younger participants (relative risk [RR] 0.32) but not for older participants. Nonwhite race was associated with a decreased risk of TKA for both younger (RR 0.32) and older (RR 0.43) participants. CONCLUSION: Our finding that nonwhites were less likely to undergo TKA than whites in adjusted analyses confirms racial differences observed in population-based studies and underscores the need for interventions to address lower use of TKA among nonwhites with OA. PMID- 26554630 TI - Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial. AB - OBJECTIVE: To evaluate tolerability, safety, and quality-of-life outcomes in non opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. oxycodone/naloxone PR. METHODS: Eligible patients (average pain intensity [numerical rating scale] >= 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. RESULTS: For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus oxycodone/naloxone PR for the PAC-SYM total score was [-0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than oxycodone/naloxone PR (P <= 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (P <= 0.024). CONCLUSIONS: Tapentadol PR had a minimal impact on bowel function (noninferior to oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. oxycodone/naloxone PR. PMID- 26554631 TI - Short Stature and Access to Lung Transplantation in the United States. A Cohort Study. AB - RATIONALE: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates. OBJECTIVES: To examine the relationship between lung transplant candidate height and waiting list outcomes. METHODS: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year. MEASUREMENTS AND MAIN RESULTS: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170 176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation. CONCLUSIONS: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height. PMID- 26554632 TI - The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice. AB - LG101506 was originally synthesized to overcome some of the undesirable side effects of rexinoids. We compared the anticarcinogenic action of LG101506 and LG100268 and for the first time showed that both drugs are useful for prevention of lung cancer in A/J mice. These molecules markedly reduced tumor number, tumor size, and total tumor burden, when chronically administered to A/J mice that had been initiated with the mutagenic carcinogen, vinyl carbamate. Moreover, LG100268 synergized with the histone deacetylase inhibitor, vorinostat, for prevention of experimental lung cancer and enhanced the effect of carboplatin/paclitaxel for treatment of experimental lung cancer. Both rexinoids diminished the percentage of high-grade, highly malignant adenocarcinomas found at autopsy. In cell culture studies, the rexinoids exhibited potent anti-inflammatory properties at nanoMolar concentrations. These drugs suppressed the ability of lipopolysaccharide to stimulate the synthesis and secretion of nitric oxide and inflammatory cytokines and chemokines, such as IL6, IL1beta, CXCL2, and CSF3, in macrophage-like RAW264.7 cells. The present results suggest that LG100268, LG101506, or a related rexinoid may have useful clinical applications in the field of oncology. PMID- 26554633 TI - Acrolein Levels in e-Cigarettes-Letter. PMID- 26554634 TI - Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern? AB - Synthetic hormones have been widely reported in treated sewage effluents, and consequently receiving aquatic environments. Ethinylestradiol (EE2) is a potent synthetic estrogen commonly used in conjunction with levonorgestrel in oral contraceptive pills. Both EE2 and levonorgestrel have been identified in the aquatic environment, but although there is a significant amount of literature on EE2, there is much less information on levonorgestrel. Using Australian prescription data as well as excretion and predicted wastewater removal rates, the concentrations of EE2 and levonorgestrel in Australian wastewater were calculated at 0.1 ng/L to 0.5 ng/L and 0.2 ng/L to 0.6 ng/L, respectively. Both compounds were analyzed in treated wastewater and surface water grab samples from 3 Southeast Queensland, Australia sites. The predicted no-effect concentration (PNEC) for EE2 of 0.1 ng/L was exceeded at most sites, with EE2 concentrations up to 2 ng/L in treated effluent, albeit quickly diluted to 0.1 ng/L to 0.2 ng/L in the receiving environment. A provisional PNEC for levonorgestrel of 0.1 ng/L derived in the present study was slightly lower than predicted effluent concentrations of 0.2 ng/L to 0.6 ng/L, indicating a potential risk of endocrine related effects in exposed aquatic species. The detection limit for levonorgestrel in the present study was 2.5 ng/L, and all samples were below detection limit. The present study's results suggest that improvements in analytical capabilities for levonorgestrel are warranted to more accurately quantify the risk of this compound in the receiving environment. Environ Toxicol Chem 2016;35:1378-1385. (c) 2015 SETAC. PMID- 26554635 TI - Restraint of Trophoblast Invasion of the Uterus by Decorin: Role in Pre eclampsia. AB - Decorin (DCN) is a leucine-rich, TGF-beta binding proteoglycan produced by mesenchymal cells including chondrocytes, dermal fibroblasts, and uterine decidual cells. It exerts multiple physiological functions including collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness. We discovered that decidua-derived DCN restrains proliferation, migration, and invasion of extravillous trophoblast (EVT) cells of the human placenta in a TGF beta-independent manner. These functions were differentially mediated by binding of DCN to multiple tyrosine kinase receptors (TKR) including EGFR, IGFR1, and VEGFR2. DCN blocked VEGFR-2 dependent EVT cell migration and endovascular differentiation by inhibiting P38MAPK and ERK1/2 pathways.We identified the avid VEGFR2 binding site in DCN protein as a 12 amino acids (LGTNPLKSSGIE) span in the Leucine-rich-repeat (LRR) 5 region of domain III. A single amino acid mutation (substitution of K to A) of DCN at this site abrogated VEGFR-2- dependent DCN actions. Also, DCN mRNA expression, measured with in situ hybridization, was selectively upregulated in decidual cells in placentas from mothers suffering from pre-eclampsia (PE), whereas the expression levels remained unchanged in chorionic villus mesenchymal cells. This difference between PE and control placentas was present at all gestational ages, indicating the pathogenic role of DCN in PE. We hypothesize that increased blood DCN levels could be a candidate biomarker for PE. PMID- 26554636 TI - Predictors affecting breast self-examination practice among undergraduate female students in Klang Valley, Malaysia. AB - AIM: Breast cancer is the most common cancer among women worldwide, including Malaysia. In developing countries, predictors affecting breast self-examination (BSE) practice are different. This cross-sectional study was conducted to determine the prevalence of BSE practice and the predictors affecting BSE practice among undergraduate female students in Klang Valley, Malaysia. MATERIAL AND METHODS: A cross-sectional study was conducted among 820 female undergraduate students to assess the BSE performance and related determinants of BSE practice in Klang Valley, Malaysia. Data were collected via a self-administered structured questionnaire that was developed for this study. RESULTS: The mean age of the respondents was 21.7 +/- 1.2 years old. Most of them were single (96.8%), Malay (91.9%) and 19.6% of the participants performed BSE regularly. Multivariate logistic regression modeling revealed that BSE performance was more likely among women who have checked their breast with a doctor (odds ratio = 2.04, P = 0.00), and women who have personal history of breast disease (odds ratio = 4.43, P = 0.03). CONCLUSION: The findings showed a low BSE practice rate among young Malaysian women. Hence, the community's breast health awareness is needed to improve breast cancer prevention among young Malaysian women. PMID- 26554637 TI - Derivation and External Validation of a Prediction Rule for Five-Year Mortality in Patients With Early Diffuse Cutaneous Systemic Sclerosis. AB - OBJECTIVE: Although diffuse cutaneous systemic sclerosis (dcSSc) is associated with a reduction in life expectancy, there are no validated prognostic models for determining 5-year mortality in patients with dcSSc. The objective of this study was to derive and validate a rule for predicting 5-year mortality in patients with early dcSSc. METHODS: We studied an inception cohort of 388 US Caucasian patients with early dcSSc (<2 years from the appearance of the first symptom). Predefined baseline variables were analyzed in a stepwise logistic regression model in order to identify factors independently associated with 5-year all-cause mortality. We rounded the beta weights to the nearest integer and summed the points assigned to each variable in order to stratify patients into low-risk (<0 points), moderate-risk (1-2 points), and high-risk (>=3 points) groups. We then applied this rule to an external validation cohort of 144 Caucasian patients with early dcSSc from the Royal Free Hospital cohort and compared stratum-specific 5 year mortality. RESULTS: Six independent predictors (rounded beta weight) comprised the model: age at first visit (points allotted: -1, 0, or 1), male sex (points allotted: 0 or 1), tendon friction rubs (points allotted: 0 or 1), gastrointestinal involvement (points allotted: 0 or 1), RNA polymerase III antibodies (points allotted: 0 or 1), and anemia (points allotted: 0 or 1). The 3 level risk stratification model performed well, with no significant differences between the US derivation cohort and the UK validation cohort. CONCLUSION: We derived and externally validated, in US and UK cohorts, an easy-to-use 6-variable prediction rule that assigns low-risk, moderate-risk, and high-risk categories for 5-year mortality in patients with early dcSSc. Only history, physical examination, and basic laboratory assessments are required. PMID- 26554638 TI - Integrating theory into disturbance interaction experiments to better inform ecosystem management. AB - Managing multiple, interacting disturbances is a key challenge to biodiversity conservation, and one that will only increase as global change drivers continue to alter disturbance regimes. Theoretical studies have highlighted the importance of a mechanistic understanding of stressor interactions for improving the prediction and management of interactive effects. However, many conservation studies are not designed or interpreted in the context of theory and instead focus on case-specific management questions. This is a problem as it means that few studies test the relationships highlighted in theoretical models as being important for ecological management. We explore the extent of this problem among studies of interacting disturbances by reviewing recent experimental studies of the interaction between fire and grazing in terrestrial ecosystems. Interactions between fire and grazing can occur via a number of pathways; one disturbance can modify the other's likelihood, intensity or spatial distribution, or one disturbance can alter the other's impacts on individual organisms. The strength of such interactions will vary depending on disturbance attributes (e.g. size or intensity), and this variation is likely to be nonlinear. We show that few experiments testing fire-grazing interactions are able to identify the mechanistic pathway driving an observed interaction, and most are unable to detect nonlinear effects. We demonstrate how these limitations compromise the ability of experimental studies to effectively inform ecological management. We propose a series of adjustments to the design of disturbance interaction experiments that would enable tests of key theoretical pathways and provide the deeper ecological understanding necessary for effective management. Such considerations are relevant to studies of a broad range of ecological interactions and are critical to informing the management of disturbance regimes in the context of accelerating global change. PMID- 26554639 TI - The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients. AB - Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib. PMID- 26554640 TI - Insights from Cardiac Mechanics after Three Decades from Successfully Repaired Aortic Coarctation. AB - BACKGROUND AND AIMS: Patients who underwent a successful repair of the aortic coarctation show chronic hyperdynamic state and normal left ventricular (LV) geometry; however, there are few data regarding the LV systolic function in the long term. Accordingly, we assessed LV systolic mechanics and factors associated with LV systolic dysfunction (LVSD) in patients with repaired CoA. METHODS: Clinical and echocardiographic data from 19 repaired CoA were analyzed 28 +/- 13 years after surgery. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were analyzed as indexes of LV circumferential and longitudinal systolic function, respectively. Echocardiographic data of CoA patients were compared with 19 patients matched for age and hypertension and 38 healthy controls. Sc-MS was considered impaired if <89%, S' if <8.5 cm/s (10th percentiles of healthy controls, respectively). RESULTS: There were no statistical differences between study groups in LV volumes, mass and geometry. LV ejection fraction and Sc-MS were similar in all groups, however, CoA group had a significantly lower peak S' in comparison with matched and healthy controls (7.1 +/- 1.3, 10.3 +/- 1.9, and 11.1 +/- 1.5, respectively; all P < 0.001). Prevalence of longitudinal LVSD defined as low S' was 84% in CoA, 13% in matched, and 5% in healthy control group (all P<0.05). Multivariate logistic regression analysis revealed that low peak S' was independently related to higher E/E' ratio and the presence of CoA. CONCLUSIONS: Patients who underwent a successful repair of CoA commonly show asymptomatic longitudinal LVSD associated with worse LV diastolic function in the long-term follow-up. PMID- 26554641 TI - The Ontology of Determination: From Descartes to Spinoza. AB - This paper argues that Spinoza's notions of "conatus" and "power of acting" are derived by means of generalization from the notions of "force of motion" and "force of determination" that Spinoza discussed in his Principles of Cartesian Philosophy to account for interactions among bodies (impacts) on the basis of their degrees of contrariety. I argue that in the Ethics, Spinoza's ontology entails that interactions must always be accounted for in terms of degrees of "agreement or disagreement in nature" among interacting things. The notion of "power of acting" is used to express the extent to which a thing's conatus is aided or restrained by external causes on the basis of its degree of agreement or disagreement in nature with them. "Power of acting" generalizes the same approach and method of resolution at the basis of the notion of "force of determination" in order to account for causal interactions not only among the simplest bodies but also among more complex individuals. PMID- 26554642 TI - Polemics in Public: Poncelet, Gergonne, Plucker, and the Duality Controversy. AB - A plagiarism charge in 1827 sparked a public controversy centered between Jean Victor Poncelet (1788-1867) and Joseph-Diez Gergonne (1771-1859) over the origin and applications of the principle of duality in geometry. Over the next three years and through the pages of various journals, monographs, letters, reviews, reports, and footnotes, vitriol between the antagonists increased as their potential publicity grew. While the historical literature offers valuable resources toward understanding the development, content, and applications of geometric duality, the hostile nature of the exchange seems to have deterred an in-depth textual study of the explicitly polemical writings. We argue that the necessary collective endeavor of beginning and ending this controversy constitutes a case study in the circulation of geometry. In particular, we consider how the duality controversy functioned as a medium of communicating new fundamental principles to a wider audience of practitioners. PMID- 26554643 TI - Keeping a House for Science: Sofia Kristensson as Matriarch and Gatekeeper at Kristineberg Zoological Station as a Scientific Household, 1877-1889. AB - Field research stations are households as a result of allegoric notions of the scientific family, and because they fulfill the purpose of a home in the field in a literal sense. They meet the practical and physical need for bed and board, as well as the emotional and intellectual need for social cohesion. I argue that this, in combination with local gender identity, opened the door for a woman of lower social strata, the daughter of a fisherman, to take upon herself the role as station household matriarch, thus gaining an integral role within an inner circle of influential scientists. Secondly, I argue that locally employed members of the research station were valued primarily for their social skills. For the sake of ensuring necessary conditions for scientific work, being abrasive was just as important as being agreeable. PMID- 26554644 TI - The Boussinesq Debate: Reversibility, Instability, and Free Will. AB - In 1877, a young mathematician named Joseph Boussinesq presented a memoire to the Academie des sciences which demonstrated that some differential equations may have more than one solution. Boussinesq linked this fact to indeterminism and to a possible solution to the free will versus determinism debate. Boussinesq's main interest was to reconcile his philosophical and religious views with science by showing that matter and motion do not suffice to explain all there is in the world. His argument received mixed criticism that addressed both his philosophical views and the scientific content of his work, pointing to the physical "realisticness" of multiple solutions. While Boussinesq proved to be able to face the philosophical criticism, the scientific objections became a serious problem, thus slowly moving the focus of the debate from the philosophical plane to the scientific one. This change of perspective implied a wide discussion on topics such as instability, the sensitivity to initial conditions, and the conservation of energy. The Boussinesq debate is an example of a philosophically motivated debate that transforms into a scientific one, an example of the influence of philosophy on the development of science. PMID- 26554645 TI - Volterra, Fascism, and France. AB - My contribution focuses on two aspects strictly related each other. On one hand, the progressive marginalization of Volterra from Italian scientific and political life after the rise of Fascism - because of his public anti-Fascist stance, both as a senator and as a professor - until his definitive exclusion on racial grounds in 1938. On the other hand, the reactions of his French colleagues and friends to this ostracism, and the support he received from them. As it emerges from several sources (Volterra's correspondence, institutional documentation, conference proceedings, etc.), it was mainly thanks to their support that he was able to escape the complete isolation and the "civil death" to which the regime condemned many of its adversaries. PMID- 26554646 TI - Models of Temporal Discounting 1937-2000: An Interdisciplinary Exchange between Economics and Psychology. AB - Today's models of temporal discounting are the result of multiple interdisciplinary exchanges between psychology and economics. Although these exchanges did not result in an integrated discipline, they had important effects on all disciplines involved. The paper describes these exchanges from the 1930s onwards, focusing on two episodes in particular: an attempted synthesis by psychiatrist George Ainslie and others in the 1970s; and the attempted application of this new discounting model by a generation of economists and psychologists in the 1980s, which ultimately ended in the diversity of measurements disappointment. I draw four main conclusions. First, multiple notions of temporal discounting must be conceptually distinguished. Second, behavioral economics is not an integration or unification of psychology and economics. Third, the analysis identifies some central disciplinary markers that distinguish modeling strategies in economics and psychology. Finally, it offers a case of interdisciplinary success that does not fit the currently dominant account of interdisciplinarity as integration. PMID- 26554647 TI - Gastrointestinal, influenza-like illness and dermatological complaints following exposure to floodwater: a cross-sectional survey in The Netherlands. AB - Extreme rainfall events may cause pluvial flooding, increasing the transmission of several waterborne pathogens. However, the risk of experiencing clinically overt infections following exposure to pluvial floodwater is poorly estimated. A retrospective cross-sectional survey was performed to quantify the occurrence of self-reported gastrointestinal, influenza-like illness (ILI) and dermatological complaints, and the frequency of visits to the general practitioner (GP), during a 4-week observation period following pluvial flooding at seven locations in The Netherlands. Questionnaires were sent to 817 flooded households, 149 (17%) of which returned the questionnaire reporting information for 199 participants. Contact with floodwater was significantly associated with increased occurrence of gastrointestinal [odds ratio (OR 4.44)], ILI (OR 2.75) and dermatological (OR 6.67) complaints, and GP visits (OR 2.72). Having hand contact with floodwater was associated with gastrointestinal and dermatological complaints, whereas ILI complaints were associated with being engaged in post-flooding cleaning operations and having walked/cycled through floodwater. This study shows that floodwater-associated diseases occur in urban settings following extreme rainfall events in a high-income country. As pluvial floods are expected to escalate in the future due to global climate change, further research is warranted to determine the disease burden of pluvial flooding and to assess the effect of different interventions, including raising awareness among stakeholders. PMID- 26554648 TI - Overexpression of major CDKN3 transcripts is associated with poor survival in lung adenocarcinoma. AB - BACKGROUND: The cyclin-dependent kinase inhibitor 3 (CDKN3) has been perceived as a tumour suppressor. Paradoxically, CDKN3 is often overexpressed in human cancer. It was unclear if CDKN3 overexpression is linked to alternative splicing variants or mutations that produce dominant-negative CDKN3. METHODS: We analysed CDKN3 expression and its association with patient survival in three cohorts of lung adenocarcinoma. We also examined CDKN3 mutations in the Cancer Genome Atlas (TCGA) and the Moffitt Cancer Center's Total Cancer Care (TCC) projects. CDKN3 transcripts were further analysed in a panel of cell lines and lung adenocarcinoma tissues. CDKN3 mRNA and protein levels in different cell cycle phases were examined. RESULTS: CDKN3 is overexpressed in non small cell lung cancer. High CDKN3 expression is associated with poor overall survival in lung adenocarcinoma. Two CDKN3 transcripts were detected in all samples. These CDKN3 transcripts represent the full length CDKN3 mRNA and a normal transcript lacking exon 2, which encodes an out of frame 23-amino acid peptide with little homology to CDKN3. CDKN3 mutations were found to be very rare. CDKN3 mRNA and protein were elevated during the mitosis phase of cell cycle. CONCLUSIONS: CDKN3 overexpression is prognostic of poor overall survival in lung adenocarcinoma. CDKN3 overexpression in lung adenocarcinoma is not attributed to alternative splicing or mutation but is likely due to increased mitotic activity, arguing against CDKN3 as a tumour suppressor. PMID- 26554649 TI - Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin. AB - BACKGROUND: A phase I trial was performed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics and immunogenicity of the anti-EpCAM immunotoxin (IT) MOC31PE in cancer patients. An important part of the study was to investigate whether the addition of Sandimmune (cyclosporin, CsA) suppressed the development of anti-IT antibodies. METHODS: Patients with EpCAM-positive metastatic disease were eligible for treatment with intravenous MOC31PE using a modified Fibonacci dose escalation sequence. Maximum tolerated dose was first established without, then with intravenously administered CsA. RESULTS: Sixty three patients were treated with MOC31PE in doses ranging from 0.5 to 8 MUg kg( 1). Maximum tolerated dose was 8 MUg kg(-1) for MOC31PE alone, and 6.5 MUg kg(-1) when combined with CsA. The dose-limiting adverse event was reversible liver toxicity. No radiological complete or partial responses were observed, whereas stable disease was seen in 36% of the patients receiving MOC31PE only. The pharmacokinetic profile of MOC31PE was characterised by linear kinetics and with a half-life of ~3 h. The addition of CsA delayed the generation of anti-IT antibodies. CONCLUSIONS: Intravenous infusion of MOC31PE can safely be administered to cancer patients. Immune suppression with CsA delays the development of anti-MOC31PE antibodies. The antitumour effect of MOC31PE warrants further evaluation in EpCAM-positive metastatic disease. PMID- 26554650 TI - Age as an independent prognostic factor for survival of localised synovial sarcoma patients. AB - BACKGROUND: We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients. METHODS: Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan-Meier survival curves and multivariable Cox-proportional hazards modelling. RESULTS: A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3+/-4.6%, 73.0+/-3.8%, 54.7+/-3.6%, and 43.0+/-7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups. CONCLUSIONS: We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment. PMID- 26554651 TI - A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium. AB - BACKGROUND: Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort). METHODS: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated. RESULTS: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN). CONCLUSIONS: The combination of eribulin and gemcitabine was well tolerated at the RP2D. PMID- 26554653 TI - Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study. AB - BACKGROUND: Studies document that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. However, studies on the direct association of magnesium with pancreatic cancer are few and findings are inconclusive. In this study, we aimed to investigate the longitudinal association between magnesium intake and pancreatic cancer incidence in a large prospective cohort study. METHOD: A cohort of 66,806 men and women aged 50-76 years at baseline who participated in the VITamins And Lifestyle (VITAL) study was followed from 2000 to 2008. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatic cancer incidence by magnesium intake categories. RESULT: During an average of 6.8-year follow-up, 151 participants developed pancreatic cancer. Compared with those who met the recommended dietary allowance (RDA) for magnesium intake, the multivariable-adjusted HRs (95% CIs) for pancreatic cancer were 1.42 (0.91, 2.21) for those with magnesium intake in the range of 75-99% RDA and 1.76 (1.04, 2.96) for those with magnesium intake <75% RDA. Every 100 mg per day decrement in magnesium intake was associated with a 24% increase in the incidence of pancreatic cancer (HR: 1.24; 95% CI: 1.02, 1.50; P(trend)=0.03). The observed inverse associations appeared not to be appreciably modified by age, gender, body mass index, and non-steroidal anti-inflammatory drug use but appeared to be limited to those taking magnesium supplementation (from multivitamins or individual supplement). CONCLUSIONS: Findings from this prospective cohort study indicate that magnesium intake may be beneficial in terms of primary prevention of pancreatic cancer. PMID- 26554652 TI - Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials. AB - BACKGROUND: PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. METHODS: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. RESULTS: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. CONCLUSIONS: PI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. PMID- 26554654 TI - Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. AB - BACKGROUND: Neoadjuvant chemotherapy (NACT) is widely used as an efficient breast cancer treatment. Ideally, a pathological complete response (pCR) can be achieved. Up to date, there is no reliable way of predicting a pCR. For the first time, we explore the ability of minimal invasive biopsy (MIB) techniques to diagnose pCR in patients with clinical complete response (cCR) to NACT in this study. This question is of high clinical relevance because a reliable pCR prediction could have direct implications for clinical practice. METHODS: In all, 164 patients were included in this review-board approved, multicenter pooled analysis of prospectively assembled data. Core-cut (CC)-MIB or vacuum-assisted (VAB)-MIB were performed after NACT and before surgery. Negative predictive values (NPV) and false-negative rates (FNR) to predict a pCR in surgical specimen (diagnose pCR through MIB) were the main outcome measures. RESULTS: Pathological complete response in surgical specimen was diagnosed in 93 (56.7%) cases of the whole cohort. The NPV of the MIB diagnosis of pCR was 71.3% (95% CI: (63.3%; 79.3%)). The FNR was 49.3% (95% CI: (40.4%; 58.2%)). Existence of a clip marker tended to improve the NPV (odds ratio 1.98; 95% CI: (0.81; 4.85)). None of the mammographically guided VABs (n=16) was false-negative (FNR 0%, NPV 100%). CONCLUSIONS: Overall accuracy of MIB diagnosis of pCR was insufficient to suggest changing clinical practice. However, subgroup analyses (mammographically guided VABs) suggest a potential capacity of MIB techniques to precisely diagnose pCR after NACT. Representativity of MIB could be a crucial factor to be focused on in further analyses. PMID- 26554656 TI - The presence of lymphovascular and perineural infiltration after neoadjuvant therapy and oesophagectomy identifies patients at high risk for recurrence. AB - BACKGROUND: In patients treated for oesophageal cancer the importance of lymphovascular and perineural invasion (PNI) after neoadjuvant therapy has yet to be established. The aim of this study was to assess the incidence and prognostic significance of these factors in a consecutive series of patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) who underwent neoadjuvant therapy followed by oesophagectomy. METHODS: Clinical and pathology results from patients with potentially curable adenocarcinoma, or squamous cell carcinoma of the oesophagus or GOJ were reviewed. Patients were treated with neoadjuvant chemotherapy or chemoradiation followed by transthoracic oesophagectomy and two field lymphadenectomy. The presence of venous invasion (VI), lymph vessel invasion (LI) and perineural invasion (PNI) were correlated with clinical outcomes. RESULTS: A total of 396 patients underwent oesophagectomy after neoadjuvant therapy for oesophageal cancer. Venous invasion was identified in 150 (38%) of patients, LI in 203 (51%) patients and PNI in 204 (52%) patients. In all, 123 (31%) patients had no evidence of either VI, LI or PNI. A total of 96 (24%) had a combination of two factors and 94 (24%) had all three factors. The presence of VI, LI and PNI was significantly related to tumour stage (P=0.001). Median overall survival was 170.8 months when all three factors were absent, 44.0 months when one factor was present, 27.1 months when two factors were present and 16.0 months when all were present. Multivariate analyses revealed VI, LI and PNI or a combination of these factors were independent predictors of prognosis. CONCLUSIONS: In oesophageal cancer patients treated with neoadjuvant therapy followed by oesophagectomy the presence of VI, LI and PNI has an important prognostic impact and may identify patients at high risk of recurrence who would benefit from adjuvant therapies. PMID- 26554655 TI - Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study. AB - BACKGROUND: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521,330 total participants (approximately 370,000 women) aged 25-70 years at recruitment from 1992 to 2000. METHODS: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. RESULTS: After a mean follow-up of 3.6 years (+/-3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (?5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, P(trend)=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. CONCLUSIONS: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users. PMID- 26554657 TI - Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy. AB - BACKGROUND: Pathologically low-risk endometrial cancer patients do not receive postoperative treatment; however, 10-15% of these patients show recurrence with poor prognosis. We evaluated the clinical importance of cyclin-dependent kinase 4/6 (CDK4/6) activity, and its significance as a novel biomarker for the prognosis and chemo-sensitivity of endometrioid endometrial carcinoma (EEC). METHODS: Cyclin-dependent kinase 4/6 expression and enzyme activity in 109 tumour samples from patients with EEC were examined with a cell-cycle profiling (C2P) assay. CDK4/6-specific activity (CDK4/6SA) was determined, and its relationship with clinicopathological factors and expression of Ki-67 was analysed. RESULTS: CDK4/6-specific activity was significantly correlated with Ki-67 (P=0.035), but not with any other clinicopathological characteristics. CDK4/6SA was significantly higher (P=0.002) in pathologically low-risk patients (not receiving adjuvant chemotherapy, n=74) than in intermediate- or high-risk patients (receiving adjuvant chemotherapy, n=35). In addition, patients with high CDK4/6SA (>3.0) showed significantly (P=0.024) shorter progression-free survival (PFS) than those with low CDK4/6SA (<3.0). Although Ki-67 expression itself was not a marker for prognosis, the combination of high CDK4/6SA and high Ki-67 expression (>15%) was robustly associated with shorter PFS (P=0.015), and this combination was an independent poor prognostic factor in the low-risk group. Inversely, in the intermediate-/high-risk group, patients with high CDK4/6SA had a tendency of a more favourable prognosis compared with patients with low CDK4/6SA (P=0.063). CONCLUSIONS: CDK4/6-specific activity can be used as a biomarker to predict prognosis and, possibly, chemo-sensitivity. The combination of Ki-67 expression might strengthen the clinical usefulness of CDK4/6SA as a biomarker. PMID- 26554658 TI - Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis. AB - BACKGROUND: Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. METHODS: We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. RESULTS: The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL 6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. CONCLUSIONS: Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients. PMID- 26554659 TI - A Bio-Acoustic Levitational (BAL) Assembly Method for Engineering of Multilayered, 3D Brain-Like Constructs, Using Human Embryonic Stem Cell Derived Neuro-Progenitors. AB - A bio-acoustic levitational assembly method for engineering of multilayered, 3D brainlike constructs is presented. Acoustic radiation forces are used to levitate neuroprogenitors derived from human embryonic stem cells in 3D multilayered fibrin tissue constructs. The neuro-progenitor cells are subsequently differentiated in neural cells, resulting in a 3D neuronal construct with inter and intralayer neurite elongations. PMID- 26554660 TI - The Spectrum of Interstitial Lung Disease in Connective Tissue Disease. AB - Interstitial lung disease (ILD) is a common cause of morbidity and mortality in patients with connective tissue disease (CTD). In a minority of patients the ILD may be the presenting (or only) manifestation of an underlying CTD. Diagnosis of CTD-related ILD relies on a multidisciplinary team including pulmonologists, pathologists, radiologists, and rheumatologists, as the imaging and pathologic findings may be indistinguishable from idiopathic interstitial pneumonias. Moreover, many patients with ILD are suspected of having an underlying CTD but do not meet all of the necessary criteria for a specific disorder. This article provides a pattern-based approach to the imaging of CTD-related ILD and also reviews relevant clinical, pathologic, and serologic data that radiologists should be familiar with as part of a multidisciplinary team. PMID- 26554661 TI - The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis. AB - BACKGROUND: Data from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression. OBJECTIVE: We designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population. METHODS: The Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (<275 ng/dl). CCTA performed at baseline and after 12 months of therapy will determine the effects of testosterone on the progression of the total volume of noncalcified plaques. All scans are evaluated at a central reading center by an investigator blinded to treatment assignment. RESULTS: A total of 165 men were enrolled. The average age is 71.1 years, and the average BMI is 30.7. About 9% of men had a history of myocardial infarction, 6% angina, and 10% coronary artery revascularization. A majority reported hypertension and/or high cholesterol; 31.8% reported diabetes. Total noncalcified plaque at baseline showed a slight but nonsignificant trend toward lower plaque volume with higher serum testosterone concentrations (P=0.12). CONCLUSION: The Cardiovascular Trial will test the hypothesis that testosterone therapy inhibits coronary plaque progression, as assessed by serial CCTA. PMID- 26554663 TI - Multimodality imaging of spontaneous coronary artery dissection: case studies of the Massachusetts General Hospital. PMID- 26554662 TI - Quantitative analysis of the side-branch orifice after bifurcation stenting using en-face processing of OCT images: a comparison between Xience V and Resolute Integrity stents. AB - OBJECTIVE: Methods for intravascular assessment of the side-branch (SB) orifice after stenting are not readily available. The aim of this study was to assess the utility of an en-face projection processing for optical coherence tomography (OCT) images for SB evaluation. METHODS: Measurements of the SB orifice obtained using en-face OCT images were validated using a phantom model. Linear regression modeling was applied to estimated area measurements made on the en-face images. The SB orifice was then analyzed in 88 patients with bifurcation lesions treated with either Xience V (everolimus-eluting stent) or Resolute Integrity [zotarolimus-eluting stent (ZES)]. The SB orifice area (A) and the area obstructed by struts (B) were calculated, and the %open area was evaluated as (A B)/A*100. RESULTS: Linear regression modeling demonstrated that the observed departures of the intercept and slope were not significantly different from 0 ( 0.12 +/- 0.22, P=0.59) and 1 (1.01 +/- 0.06, R(2)=0.88, P=0.87), respectively. In cases without SB dilatation, the %open area was significantly larger in the everolimus-eluting stent group (n=25) than in the ZES group [n=32; 89.2% (83.7 91.3) vs. 84.3% (78.9-87.8), P=0.04]. A significant difference in %open area between cases with and those without SB dilatation was demonstrated in the ZES group [91.4% (86.1-94.0) vs. 84.3% (78.9-87.8), P=0.04]. CONCLUSION: The accuracy of SB orifice measurement on an en-face OCT image was validated using a phantom model. This novel approach enables quantitative evaluation of the differences in SB orifice area free from struts among different stent types and different treatment strategies in vivo. PMID- 26554664 TI - Stimuli-free programmable drug release for combination chemo-therapy. AB - Combinational chemotherapy capable of targeted delivery and programmable multi drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. PMID- 26554665 TI - A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis. AB - BACKGROUND: Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. CASE PRESENTATION: We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. CONCLUSION: In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not been recognized as a result of the renal involvement of PBC. PBC and its rare complication of TIN with Fanconi syndrome should be considered in adult patients with unexplained osteomalacia even in the absence of liver dysfunction. PMID- 26554666 TI - Understanding adverse drug reactions in package leaflets - an exploratory survey among health care professionals. AB - BACKGROUND: Current German or UK package leaflets do not contain an explicit notice that the listing of side effects does not imply that they are caused by the drug. Causal interpretations by patients and lay people are frequently observed. The authors examined whether health professionals understand that there is not necessarily a causal relation between drug intake and the frequency of side effects and whether adding placebo comparison improves understanding. METHODS: Exploratory survey consisting of eight assessments, each containing 2-6 survey items, and focus groups with one survey sample using questionnaires on adverse reactions in standard package leaflets and modified package leaflets supplemented with placebo comparison. Participants were convenience samples of 379 health professionals including 153 physicians (80 gynaecologists, 124 diabetes experts - physicians, nurses, and others, 39 medical students in their last year at university, 49 first year health science and education students with completed vocational training and professional experience in various health care professions and 87 pharmacists/pharmacy students). They were asked to rate how often the different adverse reactions listed were caused by drug intake. All surveys were carried out within university seminars and postgraduate lectures from April 2014 to June 2015 in Germany. Response rate was 86 % or higher. RESULTS: Without placebo comparison, the majority of participants responded that the drug causes adverse reactions with the frequency given in the package leaflet or even more often (95 % of health science students, 100 % of medical students, 60 to 80 % of physicians and 66 % of pharmacists/pharmacy students). Simply adding placebo comparison in a table did not prevent misunderstanding. Analysis of focus groups with health science students supported the lack of understanding. CONCLUSIONS: In the present surveys, health professionals had major difficulties understanding frequency information on side effects in package leaflets. The great majority erroneously implied a causal relation between drug intake and the frequency of side effects, even though most side effects listed are symptoms commonly experienced in daily life. PMID- 26554667 TI - New Phloroglucinol Derivatives from the Fruit Tree Syzygium jambos and Their Cytotoxic and Antioxidant Activities. AB - Seven new phloroglucinol derivatives (1-7) were isolated from the fruit tree Syzygium jambos together with four known triterpenoids (8-11) and two known flavones (12 and 13). According to the spectroscopic analyses (infrared, electrospray ionization mass spectrometry (ESIMS), high-resolution ESIMS, 1D and 2D nuclear magnetic resonance), the structures of compounds 1-7 were elucidated as jambone A (1), jambone B (2), jambone C (3), jambone D (4), jambone E (5), jambone F (6), and jambone G (7). All the isolates were determined for their cytotoxic activities on melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, and compounds 10 and 11 showed potent activities. Moreover, compounds 1, 2, 4-7, 12, and 13 exhibited weak antioxidant activities under ferric-reducing antioxidant power and 2,2-diphenyl-1 picryhydrazyl radical-scavenging assays. PMID- 26554669 TI - Observation of unusual slow-relaxation of the magnetisation in a Gd-EDTA chelate. AB - A Gadolinium EDTA chelate displays characteristic isotropic behaviour common of Gd(III) complexes under zero applied magnetic field, and anisotropic behaviour arising from dipolar coupling and weak spin-phonon coupling under an applied magnetic field. This surprising magnetic behaviour for Gd(III) is investigated using SQUID magnetometry and rationalized through theoretical calculations. PMID- 26554668 TI - Diagnositic value of pelvic enthesitis on MRI of the sacroiliac joints in enthesitis related arthritis. AB - BACKGROUND: To determine the prevalence and diagnostic value of pelvic enthesitis on MRI of the sacroiliac (SI) joints in enthesitis related arthritis (ERA). METHODS: We retrospectively studied 143 patients aged 6-18 years old who underwent MRI of the SI joints for clinically suspected sacroiliitis between 2006 2014. Patients were diagnosed with ERA according to the International League of Associations for Rheumatology (ILAR) criteria. All MRI studies were reassessed for the presence of pelvic enthesitis, which was correlated to the presence of sacroiliitis on MRI and to the final clinical diagnosis. The added value for detection of pelvic enthesitis and fulfilment of criteria for the diagnosis of ERA was studied. RESULTS: Pelvic enthesitis was seen in 23 of 143 (16 %) patients. The most commonly affected sites were the entheses around the hip (35 % of affected entheses) and the retroarticular interosseous ligaments (32 % of affected entheses). MRI showed pelvic enthesitis in 21 % of patients with ERA and in 13 % of patients without ERA. Pelvic enthesitis was seen on MRI in 7/51 (14 %) patients with clinically evident enthesitis, and 16/92 (17 %) patients without clinically evident enthesitis. In 7 of 11 ERA-negative patients without clinical enthesitis but with pelvic enthesitis on MRI, the ILAR criteria could have been fulfilled, if pelvic enthesitis on MRI was included in the criteria. There is a high correlation between pelvic enthesitis and sacroiliitis, with sacroiliitis present in 17/23 (74 %) patients with pelvic enthesitis. CONCLUSIONS: Pelvic enthesitis may be present in children with or without clinically evident peripheral enthesitis. There is a high correlation between pelvic enthesitis and sacroiliitis on MRI of the sacroiliac joints in children. As pelvic enthesitis indicates active inflammation, it may play a role in assessment of the inflammatory status. Therefore, it should be carefully sought and noted by radiologists examining MRI of the sacroiliac joints in children. PMID- 26554670 TI - The effect of Transcranial Direct Current Stimulation in addition to Tinnitus Retraining Therapy for treatment of chronic tinnitus patients: a study protocol for a double-blind controlled randomised trial. AB - BACKGROUND: Currently, there still is no treatment that eliminates tinnitus in all patients. Recent studies have shown that Tinnitus Retraining Therapy (TRT) significantly improves quality of life for tinnitus patients. Also, several studies have reported that transcranial Direct Current Stimulation (tDCS) has a positive effect on attention, working memory, long-term memory and other cognitive processes. The aim of this randomised placebo-controlled double-blind study is to evaluate the added effect of tDCS to TRT in chronic tinnitus patients. To our knowledge, this is the first study to combine both methods. METHODS: Patients with chronic, non-pulsatile tinnitus will be randomised in two treatment groups: TRT and real tDCS versus TRT and sham tDCS. Evaluations will take place at baseline before therapy starts, at the end of the TRT and 3 months after therapy starts. The Tinnitus Functional Index will be used as the primary outcome measurement. Secondary outcome measurements will be the Visual Analogue Scale of Loudness, Hospital Anxiety and Depression Scale (HADS), Hyperacusis Questionnaire, psychoacoustic measurements and Event-related potential (ERP). DISCUSSION: To our knowledge this is the first study to combine TRT and tDCS. The objective is to evaluate whether tDCS can provide faster and/or more relief from the annoyance experienced in chronic tinnitus patients' daily lives. The advantage of the study is that it is double-blind and placebo-controlled. TRIAL REGISTRATION: The present study protocol was registered on 31 October 2014 at Clinicaltrials.gov: NCT02285803 . PMID- 26554671 TI - Effects of Interface Layers and Domain Walls on the Ferroelectric-Resistive Switching Behavior of Au/BiFeO3/La0.6Sr0.4MnO3 Heterostructures. AB - The electric field effects on the electric and magnetic properties in multiferroic heterostructures are important for not only understanding the mechanisms of certain novel physical phenomena occurring at heterointerfaces but also offering a route for promising spintronic applications. Using the Au/BiFeO3/La0.6Sr0.4MnO3 (Au/BFO/LSMO) multiferroic heterostructure as a model system, we investigated the ferroelectric-resistive switching (RS) behaviors of the heterostructure. Via the manipulation of the BFO ferroelectric polarizations, the nonvolatile tristate of RS is observed, which is closely related to the Au/BFO and BFO/LSMO interface layers and the highly conducting BFO domain walls (DWs). More interestingly, according to the magnetic field dependence of the RS behavior, the negative magnetoresistance effect of the third resistance state, corresponding to the abnormal current peak in current-pulse voltage hysteresis near the electric coercive field, is also observed at room temperature, which mainly arises from the possible oxygen vacancy accumulation and Fe ion valence variation in the DWs. PMID- 26554672 TI - Tolerance of Intrinsic Defects in PbS Quantum Dots. AB - Colloidal quantum dots exhibit various defects and deviations from ideal structures due to kinetic processes, although their band gap frequently remains open and clean. In this Letter, we computationally investigate intrinsic defects in a real-size PbS quantum dot passivated with realistic Cl-ligands. We show that the colloidal intrinsic defects are ionic in nature. Unlike previous computational results, we find that even nonideal, atomically nonstoichiometric quantum dots have a clean band gap without in-gap-states provided that quantum dots satisfy electronic stoichiometry. PMID- 26554673 TI - Echocardiographic and Blood Pressure Characteristics of First-Year Collegiate American-Style Football Players. AB - Echocardiographic (echo) and blood pressure (BP) reference values may help identify athletes at cardiovascular risk, yet benchmarks are inadequate for collegiate American-style football (ASF) players. Our purpose was to describe echo characteristics and BP values in collegiate ASF athletes compared with normal. First-year players (n = 80, age = 18 +/- 1 years, height = 186 +/- 7 cm, weight = 100.1 +/- 22.0 kg, body mass index = 28.7 +/- 5.0), body surface area [BSA] = 2.24 +/- 0.25; percentage fat = 16.5 +/- 9.7%) were measured for systolic and diastolic BP, and underwent echo procedures by a certified sonographer. Data analyses included simple statistics, Pearson r, frequencies in normal ranges, and t test; alpha = 0.05. Selected echo measurements (and indexed by BSA) were: left ventricular (LV) internal diameter diastole = 5.3 +/- 0.5 cm (2.4 +/- 0.3); left atrial diameter = 3.9 +/- 0.5 cm (1.8 +/- 0.2): LV end-diastolic volume = 138 +/- 30 ml (62 +/- 11); septal wall thickness = 1.0 +/- 0.2 cm (0.5 +/- 0.1); LV posterior wall thickness = 1.0 +/- 0.1 cm (0.5 +/- 0.1), LV mass = 212 +/- 46 g (95 +/- 18); and relative wall thickness = 0.39 +/- 0.07. Correlations between BSA and echo variables were significant (r = 0.26 to 0.50). Indexing by BSA reduced percentages above reference ranges from 36% to 7%. Septal wall thickness index was significantly greater in black (0.5 +/- 0.1) than nonblack (0.4 +/- 0.1) athletes. Fifty-nine athletes were hypertensive or prehypertensive, and diastolic BP was significantly greater in black (76 +/- 10 mm Hg) compared with nonblack athletes (71 +/- 8 mm Hg). ASF athletes demonstrated LV wall thicknesses and cavity sizes consistent with sport-training hypertrophy but which were unremarkable when indexed by BSA. Ethnicity generally did not influence echo variables. No ASF players were identified with cardiac dysfunction or disease. PMID- 26554674 TI - [Nutrition and health in the era of globalisation]. PMID- 26554675 TI - [Nutrition and health: the recipe of Italian epidemiology]. PMID- 26554676 TI - [Historic origins of the mediterranean diet: the Seven Countries Study of Cardiovascular Diseases]. PMID- 26554677 TI - [Food and cancer prognosis]. PMID- 26554678 TI - [A look at the future: trades, climate change, and nutrition in Asia]. PMID- 26554679 TI - [Pesticides, food and health]. PMID- 26554680 TI - [Reduction of meat consumption and greenhouse gas emissions associated with health benefits in Italy]. AB - BACKGROUND: the reduction in red meat consumption has been proposed as one of the climate change mitigation policies associated to health benefits. In the developed world, red meat consumption is above the recommended intake level. OBJECTIVES: the aim is to evaluate health benefits, in term of mortality decline, associated to different bovine meat consumption reduction scenarios and the potential reduction in greenhouse gas (GHG) emissions. DESIGN: meat consumption in Italy has been estimated using the Italian National Food Consumption Survey INRAN-SCAI (2005-2006) and the Multipurpose survey on household (2012) of the Italian National Institute for Statistics. Colorectal cancer and stoke mortality data are derived from the national survey on causes of death in 2012. Bovine meat consumption risk function has been retrieved from systematic literature reviews. Mean meat consumption in Italy is equal to 770 grams/week; gender and geographical variations exist: 69 per cent of the adult population are habitual bovine meat consumers; males have an average intake of over 400 grams/week in all areas of Italy (with the exception of the South), while females have lower intakes (360 grams per week), with higher consumption in the North-West (427 gr) and lower in the South of Italy. Four scenarios of reduction of bovine meat consumption (20%, 40%, 50% e 70%, respectively) have been evaluated and the number of avoidable deaths by gender and area of residence have been estimated. GHG emissions attributed to bovine meat adult consumption have been estimated to be to 10 gigagrams CO2-eq. RESULTS: from low to high reduction scenario, the percentage of avoidable deaths ranged from 2.1% to 6.5% for colorectal cancer and from 1.6% to 5.6% for stroke. Health benefits were greatest for males and for people living in the North-Western regions of Italy. CONCLUSIONS: in Italy, in order to adhere to bovine meat consumption recommendations and to respect EU GHG emission reduction targets, scenarios between 50% and 70% need to be adopted. PMID- 26554681 TI - [Dietary habits and social differences: the experience of EPIC-Italy]. AB - OBJECTIVES: to investigate the impact of socioeconomic status on dietary habits in Italy. DESIGN: large Italian multicentric prospective cohort study. SETTING AND PARTICIPANTS: more than 45,000 subjects recruited between 1993 and 1998 in five Italian centres (Turin, Varese, Florence, Naples, and Ragusa). Dietary habits, educational level, and other characteristics were collected at baseline using standardised questionnaires. MAIN OUTCOME MEASURES: dietary habits collected for the EPIC study, grouped by food type and summarised by a Mediterranean dietary index. RESULTS: we observed differences in dietary habits and in lifestyle habits by tertile of educational level. Principally, we noticed a positive association between higher education and healthy dietary habits (reduction in intake of processed meat, bread and rice, sweet drinks; increase in intake of fruit and vegetables, yoghurt, fish, olive oil, and tea). CONCLUSION: a relationship between educational level and dietary habits is confirmed also in Italy, even if differences due to gender and residence area are present. This study shows an important role of dietary habits in health inequalities of the population with lower socioeconomic status. PMID- 26554682 TI - [Health inequalities and nutrition in Italy during crisis times]. AB - OBJECTIVES: to describe systematically unhealthy patterns in nutrition behaviours, with a special focus on the impact of social, gender, geographical, and age inequalities on diet; to evaluate the potential impact of economic crisis on healthy nutrition choices and on health inequalities. DESIGN: cross sectional study within national surveys. SETTING AND PARTICIPANTS: population >=20 years, from representative samples of the Italian population in official national multipurpose surveys, in the periods 2005-2007 and 2009-2012. MAIN OUTCOME MEASURES: prevalence, population attributable fraction (PAF), and relative time variation between periods. RESULTS: wide differences on the prevalence of nutrition healthy behaviour have been found according to social position (low educated have higher consumption of meat, carbohydrates, salty food, higher breakfast skipping rates as well as lower consumption of fish), geographical area (Northern regions have higher consumption of meat, carbohydrates and fats, whereas Southern ones have lower consumption of fruit and vegetables, higher obesity, and overweight rates). Economic crises seems to have had an impact on nutrition (reduction of meat, fruit and vegetable consumption, increase on snack and legumes frequencies, less fish, and meat presence on diet), but lower than expected. Besides, if long period trends seem to increase health inequalities on nutrition, crisis seems to have had an opposite effect. CONCLUSION: unhealthy patterns seem to be present in Italian food behaviour and long time trends appear to increase them, as illustrated by the spread of obesity and overweight. Nevertheless, Mediterranean diet does not seem to be too much at risk. Economic crisis has been frequently recognized as a determinant of nutrition patterns worsening, but it has had different impacts. Furthermore, health inequalities could be decreased in crisis times. PMID- 26554683 TI - [Dietary habits and cancer: the experience of EPIC-Italy]. AB - OBJECTIVES: to investigate hypothesised relationships between diet and cancer by assessing diet as a whole, in the Italian cohort EPIC. DESIGN: multicentric prospective study. SETTING AND PARTICIPANTS: 47,749 volunteers were recruited between 1993 and 1998 in the centres of Varese and Turin (Northern Italy), Florence (Central Italy), Naples and Ragusa (Southern Italy). Information on diet and lifestyle were collected through validated questionnaires. Anthropometric measurements were taken and biological samples collected using standardised protocols. MAIN OUTCOME MEASURES: follow-up was carried out by accessing regional cancer and mortality registries, hospital discharge records, and by telephone inquiries (only for Naples). After a median follow-up of 11 years, 879 incident cases of breast cancer, 421 cases of colorectal cancer, and 152 deaths were identified. Multivariate Cox regression models were used to estimate risks in relation to dietary characteristics. RESULTS: the "Olive oil & Salad" dietary pattern, characterised by high consumption of raw vegetables and olive oil, was associated with a lower risk of overall mortality in the elderly. Adherence to a Mediterranean diet rich in vegetables and fruit was associated with reduced risk of colon cancer. Consumption of high-glycemic carbohydrates was associated with higher incidence of breast cancer and colorectal cancer. Reduced risk of colon cancer was also found in regular consumers of yoghurt. CONCLUSIONS: the accuracy and comprehensiveness of EPIC-Italy data made it possible to investigate both individual dietary components and dietary habits as a whole, to thereby provide Italians with dietary and lifestyle advice that will help them to remain healthy. PMID- 26554684 TI - [Dietary habits and cardiovascular disease: the experience of EPIC Italian collaboration]. AB - OBJECTIVES: to report and evaluate the evidence produced by the EPIC Italian collaboration (EPICOR Project) on the dietary determinants of cardiovascular diseases in Italy. DESIGN: prospective study carried out in a large Italian population, composed by cohorts recruited in Northern, Central and Southern Italy. SETTING AND PARTICIPANTS: data on dietary habits collected at the baseline observation through standardised questionnaires on 47,749 free-living adults at the time of the recruitment of the study (1993-1998). MAIN OUTCOME MEASURES: major coronary and cerebrovascular events (acute coronary syndrome, PTCA, CABG, ischemic and haemorrhagic stroke, TEA of supraortic vessels) identified at follow up. The longitudinal analyses here reported have measured risks through the use of multivariate Cox regression models, adjusted for potential confounders. RESULTS: the longitudinal analyses of EPICOR indicate that Mediterranean-oriented dietary habits, measured through specific indicators and the consumption of various typical food, are able to reduce coronary and cerebrovascular risks, and that this protection is possible even nowadays, although many changes in diet have occurred in the last decades in Italy. Habitual consumption of plant origin products, including all foods with low glycemic index, is an advantage for cardiovascular risk. CONCLUSIONS: the EPICOR Project is the largest, long-lasting Italian study on the relationship between diet and cardiovascular diseases. It is also the study with the greater number of observed variables. Its results point out the importance to support preventive programmes and industrial policies able to favour a dietary style inspired to the Italian Mediterranean tradition. PMID- 26554685 TI - [Alcohol consumption and epithelial cancer risk in the EPIC-Italy cohort]. AB - OBJECTIVES: to evaluate the association between baseline and lifetime alcohol consumption and the risk of epithelial cancer (all types) in the Italian cohort of the European Prospective Investigation into Cancer and nutrition (EPIC) study. DESIGN: prospective study carried out in a large Italian population. SETTING AND PARTICIPANTS: detailed information on the consumption of alcoholic beverages at baseline and over lifetime collected at enrolment into the EPIC study (1993-1998) by standardised questionnaires for 44,477 healthy adults. MAIN OUTCOMES MEASURES: 2,640 incident epithelial cancers identified during a mean follow-up of 11.4 years. Multivariate Cox proportional hazard models adjusted for several potential confounders were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: lifetime alcohol consumption (p for trend =0.005) was associated with epithelial cancer risk in the whole cohort. This effect was more evident in women (p =0.049) and in current smokers (p =0.012). Alcohol consumption at baseline was associated with the epithelial cancer risk in women (p for trend =0.01) and current smokers (p for trend =0.02). A significant interaction between alcohol consumption and smoke duration (p =0.015 for baseline; p =0.006 for lifetime) was identified. CONCLUSIONS: in this large Italian population, alcohol consumption, particularly lifetime, is a significant risk factor for the development of epithelial cancers. This effect appears to be modulated by smoking habits. PMID- 26554686 TI - [Determinants of eating behaviour: the contribution of twin studies]. AB - This review includes relevant twin studies conducted on eating habits and preferences, and on endophenotypes of disordered eating behaviour in general population, non-clinical settings. The twin study design is presented, along with its assumptions and possible applications in aetiological and public health epidemiology. Subsequently, the strategy for the search of the scientific literature and the exclusion criteria are reported. Then, the analysis of the studies included in this review is performed, with a brief description of targeted outcomes, twin model used, sample characteristics and findings. Finally, key messages emerging from the review are highlighted, emphasizing their value for bridging the current gaps in the understanding of determinants of eating behaviour and their mode of action. PMID- 26554687 TI - [Integrating cancer screening and primary prevention: a review]. AB - Cancer screening may represent an ideal setting for promoting healthy lifestyle. We conducted a literature review of intervention studies of primary prevention interventions implemented in the context of established screening programmes. We identified 11 trials, 3 of which conducted in Italy. A positive impact of these interventions in favouring the adoption of cancer protective dietary behaviours was observed in all studies. A limited impact was reported for physical activity, while no effect could be observed for interventions aimed to promote smoking cessation. Long term maintenance of the observed behavioural changes and the sustainability overtime of these interventions within population-based programmes should be assessed. To enhance their effectiveness, these health education programmes should include multiple strategies, integrating and combining models of individual, social, and environmental change. PMID- 26554688 TI - [Interventions for healthy diet promotion in Italy]. AB - OBJECTIVES: to describe the prevention interventions conducted by the Regional health services to promote a healthy diet. MATERIAL AND METHODS: the database ProSA, which contains prevention interventions conducted by some Italian regions, has been analysed. Programmes identified as "Diet - physical activity" were selected, and the ones that had the promotion of healthy diet in unselected populations as objective were included. Then, the programmes were analysed and described. RESULTS: a total of 87 programmes were included, 23 of which are certainly conducted during 2013-14. 91% are school-based, particularly targeted to middle schools, and 37% are based on classroom lessons. No programme made any reference to specific evidence, while 11% of them cited scientific generic but relevant papers. 15% of the programmes described some evaluation process, but only 1% has proposed a study design with controls. Limiting the analysis to the region that contributed with the largest amount of recorded programmes, it can be estimated that programmes does not reached more than 0.03% of the general population, and 4% of the school population. CONCLUSIONS: in Italy, there is not a survey system to collect preventive interventions conducted by regional health authorities. The analysis of ProSA, an experimental system, allows us to highlight that the promotion of a healthy diet is based on interventions targeting only the school population and referring to scientific evidence in a very limited way. Moreover, they seem to cover very small part of the target population. PMID- 26554689 TI - [Eating behaviours of italian adults: results of the Osservatorio epidemiologico cardiovascolare/Health Examination Survey]. AB - OBJECTIVES: to describe eating behaviours of the Italian adult population collected by the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey during 2008- 2012. DESIGN: cross-sectional survey conducted in all Italian regions; random samples of the general population, stratified by age and sex, in 23 municipalities, 220 persons every 1.5 million people. SETTING AND PARTICIPANTS: 9,111 persons examined, aged 25-79 years; participation rate of 53%; data of 8,462 persons were used in this analysis. MAIN OUTCOME MEASURES: lifestyles, risk factors, and high risk conditions were measured. Eating behaviours were assessed by the EPIC questionnaire, which includes principal foods, portions, and eating patterns; principal health eating behaviours and nutrients were described by macroareas; sodium and potassium intake were measured also by 24h urine collection; data were compared to the Mediterranean model described in the Sixties nutritional survey carried out in Nicotera, a municipality of Calabria Region, Southern Italy. RESULTS: the eating behaviours are healthy only in a part of the population: 30% have adequate intake of vegetables and fish; only 10% use cakes/sweets/desserts once a week as recommended. Energy intake from saturated fat and sugars are high. Compared to the Sixties Mediterranean model, consumption of cereals, potatoes, and legumes are reduced by half, while meats, cheeses, milk, and in particular sweets are more than doubled. CONCLUSIONS: taking into account the distribution of risk factors and high risk conditions as overweight/obesity, which affects almost 75% of the adult population, physical inactivity (30-40%), hypertension (50%), hypercholesterolemia (35%), and diabetes (7-11%), community actions for improving diet in the population are urgent. Education of the population is also needed to reduce portions and salt intake, and to use less olive oil and wine given their high caloric values, as recommended by the modern Mediterranean diet. PMID- 26554691 TI - [Breastfeeding: health, prevention, and environment]. AB - Recently, a great deal of research in the field of neuroscience and human microbiome indicates the primal period (from preconceptional up to the early years of a child's life) as crucial to the future of the individual, opening new scenarios for the understanding of the processes underlying the human health. In recent decades, the social representation of infant feeding moved in fact from the normality of breastfeeding to the normal use of artificial formulas and bottle-feeding. Even the scientific thinking and the research production have been influenced by this phenomenon. In fact, a clear dominance of studies aimed to show the benefits of breast milk compared to formula milk rather than the risks of the latter compared to the biological norm of breastfeeding. Mother milk affects infant health also through his/her microbiome. Microbial colonisation startes during intrauterine life and continues through the vaginal canal at birth, during skin to skin contact immediately after birth, with colostrum and breastfeeding. The microbial exposure of infants delivered by the mother influences the development of the child microbiota, by programming his/her future health. However, rewriting the biological normality implies also a health professional paradigm shift such as departing from the systematic separation mother-child at birth, sticking at fixed schedules for breastfeeding time and duration, as it still happens in many birth centres. Breastfeeding has economic implications and the increase of its prevalence is associated with significant reduction of avoidable hospital admissions and medical care costs, both for the child and for the mother. Success in breastfeeding is the result of complex social interactions and not simply of an individual choice. However, any successful strategy must be oriented to the mother empowerment. Therefore, health professionals and community stakeholders have to learn and practice the health promotion approach, particularly avoiding prescribing appropriate breastfeeding behaviours to the mothers, but emphasizing her needs and preferences and her values system. PMID- 26554692 TI - [Breastfeeding in the first months of life: data from the "Piccolipiu" cohorts]. PMID- 26554690 TI - [Dietary behaviour of children attending primary school in Italy found by the surveillance system "OKkio alla salute"]. AB - OBJECTIVES: to describe the dietary behaviour of children attending primary school and the school activities which promote healthy dietary habits. DESIGN OF THE STUDY: surveillance system with biannual prevalence studies. SETTING AND PARTICIPANTS: the fourth round of data collection of the surveillance system OKkio alla SALUTE took place in 2014, promoted and financed by the Ministry of Health and coordinated by the National Institute of Health in collaborations with all regions. 2,408 schools, 48,426 children and 50,638 parents participated. Stratified cluster sampling (with third grade classes as units) was used; information was collected using questionnaires completed by children, parents, teachers and head-teachers. OUTCOME MEASURES: consumption of breakfast, mid morning snack, fruit and vegetables, sweetened and gassy drinks; school initiatives to promote healthy dietary habits. RESULTS: 31% of children have an adequate breakfast and 8% skip this meal; 52% consume an energy-dense mid-morning snack; 25% do not eat fruit and vegetables daily; 41% drink sweetened/gassy beverages daily. The unhealthy dietary habits are more common among children who have less educated parents or live in the South (more deprived area of the Country). Data show an improvement in the period 2008-2014, except in the consumption of fruit and vegetables. 74% of the schools include nutritional education in the curriculum, 66% have started initiatives of healthy dietary habits and 55% distribute healthy food; 35% involve parents in their initiatives. In the schools of the South nutritional education and involvement of parents are more frequent, while the distribution of healthy food and refectories are less common. CONCLUSIONS: the high frequency of unhealthy dietary behaviour and their geographic and social inequalities show that there is a great potential for improvement. Schools are very involved in initiatives of promotion, but they need more support from the institutions and involvement of the families. PMID- 26554693 TI - [Motivational interviewing to treat overweight children and their parents in paediatrician's medical office: good results, but one year is not sufficient]. PMID- 26554694 TI - [European nutrition policy: regulatory dynamics and trajectories]. AB - In the light of the relationship between health and nutrition, this paper focuses on the policy strategy designed by the European institutions with regard to nutrition. Starting from the analysis of the World Declaration for Nutrition adopted by FAO and WHO in 1992, the main European regulatory measures adopted on the issue are analysed and some reflections are offered about their normative status (hard and soft law), as well as on some problematic aspects and implications. Moreover, the contribution focuses on two major European strategies in regulating nutrition, namely the health-in-all-policies and whole-of government approaches, characterized by the combination of heterogeneous legal instruments together with the coexistence of actions undertaken by public and private actors. The framework thus conceived - though noteworthy and commendable for several reasons - turns out to be problematic in achieving the desired goals: health protection and citizens' well-being. PMID- 26554695 TI - [The DianaWeb project and EpiChange]. PMID- 26554696 TI - [DianaWeb: a demonstration project to improve breast cancer prognosis through lifestyles]. AB - In the field of cancer prevention, the public ask to be involved more actively in scientific research and in the production of knowledge. This is leading to an increase of participatory projects in the field of epidemiology. Community-based participatory research (CBPR) has received considerable attention in the past 15 years; it is becoming a recognized and important approach in addressing health disparities in cancer prevention. The increasing accessibility of new methods of comparison, discussion and information allows to link a large number of people. The project DianaWeb was born in 2015 at the Department of Predictive Medicine and Prevention of the National Cancer Institute, Milan. This CBPR involves women with diagnosis of breast cancer (BC). DianaWeb communications are based on an interactive online platform developed "ad hoc" (www.dianaweb.org). With very few exceptions, all communication between participants and research team will be on the web. The recruitment is done through Internet, hospitals, physicians, media and word of mouth. Women can join the project independently, under the control of researchers and the aim of the study is to assess whether healthy eating and regular physical activity can improve the quality of life and increase survival rates in women with diagnosis of BC. About 50,000 Italian women with a diagnosis of BC with or without metastasis, local recurrence or second cancers; with in situ or invasive cancer, whatever the disease stage at diagnosis, whatever histological diagnosis, whatever the time elapsed since diagnosis should be recruited in the DianaWeb project. The volunteers are asked to send clinical information about their condition from diagnosis onwards, on their weight and other anthropometric measures, lifestyles and nutrition through online questionnaires. Moreover, the women enrolled in the study, after login, can access evidence-based information and results obtained during the project (individual and whole community data). Volunteers can also contribute to the growth of knowledge about lifestyles to be adopted by sharing recipes, movement strategies, how to manage the change in daily practice, which will be judged by the researchers to verify the compliance with the recommendations provided before networking. PMID- 26554698 TI - Can Acute Kidney Injury Be Considered a Clinical Quality Measure. AB - Quality indicators are measurements of healthcare outcome, process, or structure that can be used as tools to measure the quality of care and identify opportunities for improvement. Acute kidney injury (AKI) has many characteristics that make it a potential target for quality indicator development. It is common, associated with a high risk of adverse outcomes, and there are reports of gaps in the quality of care in several clinical settings despite publication of evidence based guidelines. Substantial work has already been undertaken to develop quality measures related to AKI following percutaneous coronary interventions and major surgical procedures. This paper reviews the current literature that has addressed issues of prevention or management of AKI as outcome, process, or structure quality indicators in these clinical settings. Several current controversies about the appropriateness of such indicators related to AKI are identified. Further research to strengthen the evidence-base supporting prevention and management initiatives for AKI across all relevant clinical settings is needed to clarify the role of AKI as a target for clinical quality indicators. PMID- 26554697 TI - Demonstration of Hole Transport and Voltage Equilibration in Self-Assembled pi Conjugated Peptide Nanostructures Using Field-Effect Transistor Architectures. AB - pi-Conjugated peptide materials are attractive for bioelectronics due to their unique photophysical characteristics, biofunctional interfaces, and processability under aqueous conditions. In order to be relevant for electrical applications, these types of materials must be able to support the passage of current and the transmission of applied voltages. Presented herein is an investigation of both the current and voltage transmission activities of one dimensional pi-conjugated peptide nanostructures. Observations of the nanostructures as both semiconducting and gate layers in organic field-effect transistors (OFETs) were made, and the effect of systematic changes in amino acid composition on the semiconducting/conducting functionality of the nanostructures was investigated. These molecular variations directly impacted the hole mobility values observed for the nanomaterial active layers over 3 orders of magnitude (~0.02 to 5 * 10(-5) cm(2) V(-1) s(-1)) when the nanostructures had quaterthiophene cores and the assembled peptide materials spanned source and drain electrodes. Peptides without the quaterthiophene core were used as controls and did not show field-effect currents, verifying that the transport properties of the nanostructures rely on the semiconducting behavior of the pi-electron core and not just ionic rearrangements. We also showed that the nanomaterials could act as gate electrodes and assessed the effect of varying the gate dielectric layer thickness in devices where the conventional organic semiconductor pentacene spanned the source and drain electrodes in a top-contact OFET, showing an optimum performance with 35-40 nm dielectric thickness. This study shows that these peptides that self-assemble in aqueous environments can be used successfully to transmit electronic signals over biologically relevant distances. PMID- 26554699 TI - Hyaluronic Acid Modified Tantalum Oxide Nanoparticles Conjugating Doxorubicin for Targeted Cancer Theranostics. AB - Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy. PMID- 26554700 TI - Variable electronic properties of lateral phosphorene-graphene heterostructures. AB - Phosphorene and graphene have a tiny lattice mismatch along the armchair direction, which can result in an atomically sharp in-plane interface. The electronic properties of the lateral heterostructures of phosphorene/graphene are investigated by the first-principles method. Here, we demonstrate that the electronic properties of this type of heterostructure can be highly tunable by the quantum size effects and the externally applied electric field (Eext). At strong Eext, Dirac Fermions can be developed with Fermi velocities around one order smaller than that of graphene. Undoped and hydrogen doped configurations demonstrate three drastically different electronic phases, which reveal the strongly tunable potential of this type of heterostructure. Graphene is a naturally better electrode for phosphorene. The transport properties of two-probe devices of graphene/phosphorene/graphene exhibit tunnelling transport characteristics. Given these results, it is expected that in-plane heterostructures of phosphorene/graphene will present abundant opportunities for applications in optoelectronic and electronic devices. PMID- 26554701 TI - Patients' need for information provision and perceived participation in decision making in doctor-patient consultation: Micro-cultural differences between French- and Italian-speaking Switzerland. AB - OBJECTIVES: To explore micro-cultural differences in patients' need for information provision, perceived participation in decision making, and related concepts during the doctor-patient consultation between French- and Italian speaking patients in Switzerland. METHODS: In 2012, 153 French- and 120 Italian speaking patients with chronic low back pain (cLBP) were surveyed on their need for information provision, perceived participation in decision making, cLBP knowledge, psychological empowerment, and trust in their doctor. T-tests and regression analyses with interaction terms were performed. RESULTS: Results show that French- and Italian-speaking patients significantly differed in their participation in decision making, with French-speaking patients reporting higher involvement. Need for information provision was related to empowerment among French- and to trust among Italian-speaking patients. For participation in decision making, trust was the only related concept among French-, and cLBP knowledge among Italian-speaking patients. Significant interaction terms indicate a moderation of micro-cultural background. CONCLUSION: Findings point towards differences in the relationships between individual patient characteristics (i.e. knowledge, empowerment) and relational doctor-patient characteristics (i.e. trust) and patients' need for information provision and participation in decision making between French- and Italian-speaking patients in Switzerland. PRACTICE IMPLICATIONS: Doctors should be aware of these differences when dealing with patients of different micro-cultural backgrounds. PMID- 26554702 TI - Development of novel magnetic solid phase extraction materials based on Fe3O4/SiO2/poly(acrylamide-N,N'-methylene bisacrylamide)-Pluronic L64 composite microspheres and their application to the enrichment of natamycin. AB - Novel magnetic adsorbents based on Fe3O4/SiO2/poly(acrylamide-N,N'-methylene bisacrylamide) magnetic microspheres modified with non-ionic triblock copolymer surfactant were successfully prepared as a magnetic solid phase extraction adsorbent for the determination of trace natamycin in jam samples. The adsorbent was characterized by scanning electron microscopy, transmission electron microscopy, Fourier transformed infrared spectroscopy, vibrating sample magnetometer, and X-ray diffractometer analysis, confirming that Pluronic L64 was effectively functionalized on the magnetic materials. Various experimental parameters affecting the extraction capacity were investigated including adsorbent amount, extraction time, desorption time, sample pH, and ionic strength. For recovery evaluations, the jam samples were spiked at two concentration levels of 100 and 200MUgkg(-1) of natamycin and the recovery values were in the range of 78.8-93.4%. The relative standard deviations (RSD) for the recoveries were less than 3.5%. The novel magnetic solid phase extraction method provided several advantages, such as simplicity, low environmental impact, convenient extraction procedure, and short analysis time when used for natamycin analysis. PMID- 26554703 TI - Correction: A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis. PMID- 26554704 TI - From Sensory Signals to Modality-Independent Conceptual Representations: A Probabilistic Language of Thought Approach. AB - People learn modality-independent, conceptual representations from modality specific sensory signals. Here, we hypothesize that any system that accomplishes this feat will include three components: a representational language for characterizing modality-independent representations, a set of sensory-specific forward models for mapping from modality-independent representations to sensory signals, and an inference algorithm for inverting forward models-that is, an algorithm for using sensory signals to infer modality-independent representations. To evaluate this hypothesis, we instantiate it in the form of a computational model that learns object shape representations from visual and/or haptic signals. The model uses a probabilistic grammar to characterize modality independent representations of object shape, uses a computer graphics toolkit and a human hand simulator to map from object representations to visual and haptic features, respectively, and uses a Bayesian inference algorithm to infer modality independent object representations from visual and/or haptic signals. Simulation results show that the model infers identical object representations when an object is viewed, grasped, or both. That is, the model's percepts are modality invariant. We also report the results of an experiment in which different subjects rated the similarity of pairs of objects in different sensory conditions, and show that the model provides a very accurate account of subjects' ratings. Conceptually, this research significantly contributes to our understanding of modality invariance, an important type of perceptual constancy, by demonstrating how modality-independent representations can be acquired and used. Methodologically, it provides an important contribution to cognitive modeling, particularly an emerging probabilistic language-of-thought approach, by showing how symbolic and statistical approaches can be combined in order to understand aspects of human perception. PMID- 26554705 TI - Contact angles and wettability of ionic liquids on polar and non-polar surfaces. AB - Many applications involving ionic liquids (ILs) require the knowledge of their interfacial behaviour, such as wettability and adhesion. In this context, herein, two approaches were combined aiming at understanding the impact of the IL chemical structures on their wettability on both polar and non-polar surfaces, namely: (i) the experimental determination of the contact angles of a broad range of ILs (covering a wide number of anions of variable polarity, cations, and cation alkyl side chain lengths) on polar and non-polar solid substrates (glass, Al-plate, and poly-(tetrafluoroethylene) (PTFE)); and (ii) the correlation of the experimental contact angles with the cation-anion pair interaction energies generated by the Conductor-like Screening Model for Real Solvents (COSMO-RS). The combined results reveal that the hydrogen-bond basicity of ILs, and thus the IL anion, plays a major role through their wettability on both polar and non-polar surfaces. The increase of the IL hydrogen-bond accepting ability leads to an improved wettability of more polar surfaces (lower contact angles) while the opposite trend is observed on non-polar surfaces. The cation nature and alkyl side chain lengths have however a smaller impact on the wetting ability of ILs. Linear correlations were found between the experimental contact angles and the cation-anion hydrogen-bonding and cation ring energies, estimated using COSMO-RS, suggesting that these features primarily control the wetting ability of ILs. Furthermore, two-descriptor correlations are proposed here to predict the contact angles of a wide variety of ILs on glass, Al-plate, and PTFE surfaces. A new extended list is provided for the contact angles of ILs on three surfaces, which can be used as a priori information to choose appropriate ILs before a given application. PMID- 26554706 TI - Micronized Copper Wood Preservatives: Efficacy of Ion, Nano, and Bulk Copper against the Brown Rot Fungus Rhodonia placenta. AB - Recently introduced micronized copper (MC) formulations, consisting of a nanosized fraction of basic copper (Cu) carbonate (CuCO3.Cu(OH)2) nanoparticles (NPs), were introduced to the market for wood protection. Cu NPs may presumably be more effective against wood-destroying fungi than bulk or ionic Cu compounds. In particular, Cu- tolerant wood-destroying fungi may not recognize NPs, which may penetrate into fungal cell walls and membranes and exert their impact. The objective of this study was to assess if MC wood preservative formulations have a superior efficacy against Cu-tolerant wood-destroying fungi due to nano effects than conventional Cu biocides. After screening a range of wood-destroying fungi for their resistance to Cu, we investigated fungal growth of the Cu-tolerant fungus Rhodonia placenta in solid and liquid media and on wood treated with MC azole (MCA). In liquid cultures we evaluated the fungal response to ion, nano and bulk Cu distinguishing the ionic and particle effects by means of the Cu2+ chelator ammonium tetrathiomolybdate (TTM) and measuring fungal biomass, oxalic acid production and laccase activity of R. placenta. Our results do not support the presence of particular nano effects of MCA against R. placenta that would account for an increased antifungal efficacy, but provide evidence that attribute the main effectiveness of MCA to azoles. PMID- 26554707 TI - Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach. AB - INTRODUCTION: Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT) and interpersonal psychotherapy (IPT). METHODS: 134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI), a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach. RESULTS: We found five predictors (gender, employment status, anxiety, personality disorder and quality of life) and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events) of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT) had an observed mean end-BDI of 11.8, while those who received their predicted non optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51). DISCUSSION: Depressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although the utility of the PAI approach will need to be evaluated in prospective research, this study promotes the development of a treatment selection approach that can be used in regular mental health care, advancing the goals of personalized medicine. PMID- 26554708 TI - High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs. AB - MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34 3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR 246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6-20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans. PMID- 26554709 TI - Age- and Gender Dependent Liver Fat Content in a Healthy Normal BMI Population as Quantified by Fat-Water Separating DIXON MR Imaging. AB - OBJECTIVES: To establish age- and sex-dependent values of magnetic resonance (MR) liver fat-signal fraction (FSF) in healthy volunteers with normal body-mass index (BMI). METHODS: 2-point mDIXON sequences (repetition time/echo time, 4.2msec/1.2msec, 3.1msec) at 3.0 Tesla MR were acquired in 80 healthy volunteers with normal BMI (18.2 to 25.7 kg/m2) between 20 and 62 years (10 men/10 women per decade). FSF was measured in 5 liver segments (segment II, III, VI, VII, VIII) based on mean signal intensities in regions of interest placed on mDIXON-based water and fat images. Multivariate general linear models were used to test for significant differences between BMI-corrected FSF among age subgroups. Pearson and Spearman correlations between FSF and several body measures were calculated. RESULTS: Mean FSF (%) +/- standard deviations significantly differed between women (3.91 +/- 1.10) and men (4.69 +/- 1.38) and varied with age for women/men (p-value: 0.002/0.027): 3.05 +/- 0.49/3.74 +/- 0.60 (age group 20-29), 3.75 +/- 0.66/4.99 +/- 1.30 (30-39), 4.76 +/- 1.16/5.25 +/- 1.97 (40-49) and 4.09 +/- 1.26/4.79 +/- 0.93 (50-62). FSF differences among age subgroups were significant for women only (p = 0.003). CONCLUSIONS: MR-based liver fat content is higher in men and peaks in the fifth decade for both genders. PMID- 26554710 TI - Incidence and Effects of Polypharmacy on Clinical Outcome among Patients Aged 80+: A Five-Year Follow-Up Study. AB - OBJECTIVES: Polypharmacy is a problem of growing interest in geriatrics with the increase in drug consumption in recent years, is defined according to the WHO criteria as the, ''concurrent use of five or more different prescription medication". We investigated the clinical characteristics of polypharmacy and identified the effects of polypharmacy on clinical outcome among patients aged 80+ admitted to Chinese PLA general hospital. METHODS: Older men aged >=80 years (n = 1562) were included in this study. The included participants attended a structured clinical examination and an interview carried out by a geriatrician and trained nurses. A follow-up survey in 2014 was carried out on survivors in the same way as in 2009. The clinical outcome measured were adverse drug reactions, falls, frailty, disability, cognitive impairment, mortality. The association between polypharmacy and clinical outcome was assessed by logistic regression. RESULTS: The mean (range) age of the included participants was 85.2 (80-104) years. Medication exposure was reported by 100% of the population. Mean number of medications reported in this population was 9.56+/-5.68. The prevalence of polypharmacy (>=6 medications) in the present study was 70%. At the time of the follow-up survey, an increase in the number of taken medicines had occurred among half of the survivors. The risk of different outcomes in relation to number of medications rises significantly, the odds ratios were 1.21 (95% confidence interval [CI]1.17-1.28) for adverse drug reactions, 1.18 (95% CI 1.10-1.26) for falls, 1.16 (95% CI 1.09-1.24) for disability, and 1.19 (95% CI 1.12-1.23) for mortality. There was no association between increasing number of medications and cognitive impairment. CONCLUSIONS: Our study demonstrates that polypharmacy is very common in the very old patients, and observed that number of medications was a factor associated with difference clinical outcome independently of the age, type of medications prescribed and accompanied comorbidities. PMID- 26554711 TI - Identifying Causal Risk Factors for Violence among Discharged Patients. AB - BACKGROUND: Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. METHODS: We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. RESULTS: In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85-12.65, P<0.001), instability (OR 5.41, 95% CI 3.44-8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21-16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08-0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. CONCLUSIONS: Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors causally associated with violence. PMID- 26554712 TI - Monomethylarsonous Acid (MMAIII) Has an Adverse Effect on the Innate Immune Response of Human Bronchial Epithelial Cells to Pseudomonas aeruginosa. AB - Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection. This study examined the effects on Pseudomonas aeruginosa (P. aeruginosa) induced cytokine secretion by human bronchial epithelial cells (HBEC) by inorganic sodium arsenite (iAsIII) and two major metabolites, monomethylarsonous acid (MMAIII) and dimethylarsenic acid (DMAV), at concentrations relevant to the U.S. POPULATION: Neither iAsIII nor DMAV altered P. aeruginosa induced cytokine secretion. By contrast, MMAIII increased P. aeruginosa induced secretion of IL-8, IL-6 and CXCL2. A combination of iAsIII, MMAIII and DMAV (10 pbb total) reduced IL-8 and CXCL1 secretion. These data demonstrate for the first time that exposure to MMAIII alone, and a combination of iAsIII, MMAIII and DMAV at levels relevant to the U.S. may have negative effects on the innate immune response of human bronchial epithelial cells to P. aeruginosa. PMID- 26554713 TI - Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree. AB - Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways may play an important role in the pathophysiology of BPD. PMID- 26554714 TI - Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control. AB - BACKGROUND: After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk. METHODS: A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease. RESULTS: Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 MUmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 MUmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 MUmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: -0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 MUmol/L; p = 0.045). CONCLUSIONS: Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease. PMID- 26554715 TI - The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: A meta-analysis of observational studies. AB - BACKGROUND AND AIMS: The association of vitamin D deficiency with cardiovascular disease is controversial. The present meta-analysis was performed to examine if circulating levels of 25-hydroxyvitamin D [25(OH)D] were lower in patients with peripheral artery disease (PAD) when compared to non-PAD controls. METHODS: A comprehensive database search was conducted in Web of science, Scopus, PubMed, EMBASE and The Cochrane Library to identify observational studies reporting 25(OH)D concentrations in PAD patients and non-PAD participants. Data extraction and study quality assessments were conducted independently. A random-effects model was used to meta-analyse extracted data and generate standardized mean differences (SMDs) in circulating 25(OH)D levels between PAD patients and non-PAD controls. Subgroup analyses were conducted focussing on patients presenting with intermittent claudication (IC) and critical limb ischaemia (CLI). RESULTS: Six case-control studies assessing 6418 individuals fulfilled the inclusion criteria. Two studies were considered to be of moderate methodological quality and four were considered to be of high quality. A meta-analysis of data from 1217 PAD patients and 5201 non-PAD participants showed that circulating 25(OH)D concentrations were lower in PAD patients compared with non-PAD participants (SMD = -0.32, 95% CI: -0.58, -0.05; P = 0.02). Subgroup analyses showed that 25(OH)D levels were significantly lower among PAD patients with CLI, but not IC, when compared to non-PAD controls (SMD = -1.29, 95% CI: -1.66, -0.91; P < 0.001 and SMD = -0.01, 95% CI: -0.15, 0.13; P=0.88, respectively). CONCLUSIONS: This meta analysis suggests that low levels of circulating 25(OH)D are associated with PAD presence, particularly in patients presenting with CLI. These data suggest the possibility that vitamin D insufficiency may contribute to the development of more advanced PAD although this remains to be confirmed. PMID- 26554716 TI - Performance of an improperly sized and stretched-out loose-fitting powered air purifying respirator: Manikin-based study. AB - The objective of this study was to investigate the protection level offered by a Powered Air-Purifying Respirator (PAPR) equipped with an improperly sized or stretched-out loose-fitting facepiece using constant and cyclic flow conditions. Improperly sized PAPR facepieces of two models as well as a stretched-out facepiece were tested. These facepieces were examined in two versions: with and without exhaust holes. Loose-fitting facepieces (size "large") were donned on a small manikin headform and challenged with sodium chloride (NaCl) aerosol particles in an exposure chamber. Four cyclic flows with mean inspiratory flows (MIFs) of 30, 55, 85, and 135 L/min were applied using an electromechanical Breathing Recording and Simulation System (BRSS). The manikin Fit Factor (mFF) was determined as the ratio of aerosol concentrations outside (Cout) to inside (Cin) of the facepiece, measured with a P-Trak condensation particle counter (CPC). Results showed that the mFF decreased exponentially with increasing MIF. The mFF values of the stretched-out facepiece were significantly lower than those obtained for the undamaged ones. Facepiece type and MIF were found to significantly affect the performance of the loose-fitting PAPR. The effect of the exhaust holes was less pronounced and depended on the facepiece type. It was concluded that an improperly sized facepiece might potentially offer relatively low protection (mFF < 250) at high to strenuous workloads. The testing was also performed at a constant inhalation flow to explore the mechanism of the particle facepiece interaction. Results obtained with cyclic flow pattern were consistent with the data generated when testing the loose-fitting PAPR under constant flow conditions. The time-weighted average values of mFF calculated from the measurements conducted under the constant flow regime were capable of predicting the protection under cyclic flow regime. The findings suggest that program administrators need to equip employees with properly sized facepieces and remove stretched-out ones from workplace. Manufacturers should emphasize the importance of proper sizing with their user instructions. PMID- 26554717 TI - Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes). AB - The environmental risks of five engineered nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes) were quantified in water, soils, and sediments using probabilistic Species Sensitivity Distributions (pSSDs) and probabilistic predicted environmental concentrations (PECs). For water and soil, enough ecotoxicological endpoints were found for a full risk characterization (between 17 and 73 data points per nanomaterial for water and between 4 and 20 for soil) whereas for sediments, the data availability was not sufficient. Predicted No Effect Concentrations (PNECs) were obtained from the pSSD and used to calculate risk characterization ratios (PEC/PNEC). For most materials and environmental compartments, exposure and effect concentrations were separated by several orders of magnitude. Nano-ZnO in freshwaters and nano-TiO2 in soils were the combinations where the risk characterization ratio was closest to one, meaning that these are compartment/ENM combinations to be studied in more depth with the highest priority. The probabilistic risk quantification allows us to consider the large variability of observed effects in different ecotoxicological studies and the uncertainty in modeled exposure concentrations. The risk characterization results presented in this work allows for a more focused investigation of environmental risks of nanomaterials by consideration of material/compartment combinations where the highest probability for effects with predicted environmental concentrations is likely. PMID- 26554718 TI - QQ-SNV: single nucleotide variant detection at low frequency by comparing the quality quantiles. AB - BACKGROUND: Next generation sequencing enables studying heterogeneous populations of viral infections. When the sequencing is done at high coverage depth ("deep sequencing"), low frequency variants can be detected. Here we present QQ-SNV (http://sourceforge.net/projects/qqsnv), a logistic regression classifier model developed for the Illumina sequencing platforms that uses the quantiles of the quality scores, to distinguish true single nucleotide variants from sequencing errors based on the estimated SNV probability. To train the model, we created a dataset of an in silico mixture of five HIV-1 plasmids. Testing of our method in comparison to the existing methods LoFreq, ShoRAH, and V-Phaser 2 was performed on two HIV and four HCV plasmid mixture datasets and one influenza H1N1 clinical dataset. RESULTS: For default application of QQ-SNV, variants were called using a SNV probability cutoff of 0.5 (QQ-SNV(D)). To improve the sensitivity we used a SNV probability cutoff of 0.0001 (QQ-SNV(HS)). To also increase specificity, SNVs called were overruled when their frequency was below the 80(th) percentile calculated on the distribution of error frequencies (QQ-SNV(HS-P80)). When comparing QQ-SNV versus the other methods on the plasmid mixture test sets, QQ SNV(D) performed similarly to the existing approaches. QQ-SNV(HS) was more sensitive on all test sets but with more false positives. QQ-SNV(HS-P80) was found to be the most accurate method over all test sets by balancing sensitivity and specificity. When applied to a paired-end HCV sequencing study, with lowest spiked-in true frequency of 0.5%, QQ-SNV(HS-P80) revealed a sensitivity of 100% (vs. 40-60% for the existing methods) and a specificity of 100% (vs. 98.0-99.7% for the existing methods). In addition, QQ-SNV required the least overall computation time to process the test sets. Finally, when testing on a clinical sample, four putative true variants with frequency below 0.5% were consistently detected by QQ-SNV(HS-P80) from different generations of Illumina sequencers. CONCLUSIONS: We developed and successfully evaluated a novel method, called QQ SNV, for highly efficient single nucleotide variant calling on Illumina deep sequencing virology data. PMID- 26554719 TI - Distribution and molecular characteristics of Vibrio cholerae O1 El Tor isolates recovered in Guangdong Province, China, 1961-2013. AB - China's Guangdong Province is located along the same latitude as Kolkata, India and Dhaka, Bangladesh, and is also considered a source of epidemic cholera. However, molecular description and the genetic relationships between Vibrio cholerae O1 El Tor isolates in Guangdong remain unclear. In this study, 381 clinical V. cholerae O1 isolates recovered from cholera cases presenting in Guangdong between 1961 and 2013 were investigated by PCR, amplicon sequencing and pulsed-field gel electrophoresis (PFGE). During this time frame, four distinct epidemic periods (1-4) were observed based on the different dominant serotype leading its epidemic, correspond to years; or time periods from/to 1961-1969, 1978-1989, 1990-2000, 2001-2013, respectively. Molecular analysis of representative isolates indicated that a single dominating clone was associated with each epidemic stage. All isolates from periods 1 and 2 carried the typical El Tor ctxB; this allele was displaced by classical ctxB beginning in 1993. However all isolates carried the El Tor-specific toxin-coregulated pili subunit A (tcpA). Isolates were grouped into five clusters on the basis of Not I enzyme digested PFGE, and the first four clusters were associated with specific periods, cluster I (period 1), II (period 3), III (period 2) and IV (period 4), respectively. While cluster V consisted of isolates from all four epidemic periods, but was most heterogeneous in appearance. Our data indicate genetic variations that shape the relationship among emerging isolates of V. cholerae O1 in Guangdong Province contribute to the 7th global pandemic. PMID- 26554720 TI - Circulating Progenitor Cells and Childhood Cardiovascular Disease. AB - Circulating progenitor cells have been extensively studied in the context of heart disease in adults. In these patients, they have been demonstrated to be markers of myocardial injury and recovery as well as potential therapeutic agents. However, studies in children are much more limited. Here we review current knowledge pertaining to circulating progenitor cells in the context of childhood cardiovascular disease. Priorities for further research are also highlighted. PMID- 26554721 TI - Inhibition of murine breast cancer growth and metastasis by survivin-targeted siRNA using disulfide cross-linked linear PEI. AB - Biodegradable disulfide-containing polyethyleneimine (PEI) derivatives showed great potential as siRNA vectors for the treatment of cancer due to the reduction sensitive property. In this study, we developed and characterized a hyperbranched disulfide cross-linked PEI (lPEI-SS) based on linear PEI (lPEI) by ring-opening reaction of propylene sulfide. We evaluated the efficiency of lPEI-SS as a siRNA vector in vitro with luciferase reporter gene system, and investigated the anti tumor efficacy of survivin-targeted siRNA (siRNA(sur)) on 4T1 murine breast cancer model using lPEI-SS synthesized here. Results from cytotoxicity and hemolysis assay proved that lPEI-SS showed favorable cell and blood compatibility. lPEI-SS/siRNA polyplexes prepared under the optimized condition were compact spherical particles with the average size of 229.0nm and zeta potential of 42.67mV. Cellular uptake of lPEI-SS/siRNA polyplexes was significantly improved due to the higher branching degree of lPEI-SS over the parent lPEI. lPEI-SS/siRNA(sur) exhibited great anti-proliferation effect on 4T1 cell line, which was found to be caused by the induction of apoptosis. Most importantly, results of tumor volume, tumor weight and histological observation demonstrated that lPEI-SS/siRNA(sur) polyplexes effectively inhibited the tumor growth and metastasis of 4T1 murine breast cancer model. PMID- 26554724 TI - Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption. AB - Trauma induced neuroinflammation plays a key role in the development of postoperative cognitive dysfunction (POCD). The blood-brain barrier (BBB), a highly specialized endothelial layer, is exquisitely sensitive to inflammatory insults, which can result in numerous neurocognitive syndromes. While brain mast cells are the "first responder" in the injury, the functional interactions between mast cells and the BBB remain poorly understood. Our results demonstrate that tibial fracture surgery can induce cognitive impairment relating to an inflammatory response and destabilization of the BBB. Disodium cromoglycate (cromolyn)--which acts as a mast cell stabilizer--inhibited this effect. Specifically, cromolyn resulted in ameliorated cognitive ability, decrease of inflammatory cytokines and increase of BBB stability. Taken together, these results suggest that activated mast cells contributed to central nervous system inflammation and cognitive dysfunction by promoting BBB disruption, and interactions between mast cells and the BBB could constitute a new and unique therapeutic target for POCD. PMID- 26554725 TI - Induction of depression-related behaviors by reactivation of chronic Toxoplasma gondii infection in mice. AB - Although Toxoplasma gondii (T. gondii) infection is relevant to many psychiatric disorders, the fundamental mechanisms of its neurobiological correlation with depression are poorly understood. Here, we show that reactivation of chronic infection by an immunosuppressive regimen caused induction of depressive-like behaviors without obvious sickness symptoms. However, the depression-related behaviors in T. gondii-infected mice, specifically, reduced sucrose preference and increased immobility in the forced-swim test were observed at the reactivation stage, but not in the chronic infection. Interestingly, reactivation of T. gondii was associated with production of interferon-gamma and activation of brain indoleamine 2, 3-dioxygenase, which converts tryptophan to kynurenine and makes it unavailable for serotonin synthesis. Furthermore, serotonin turnover to its major metabolite, 5-hydroxyindoleacetic acid, was also enhanced at the reactivation stage. Thus, enhanced tryptophan catabolic shunt and serotonin turnover may be implicated in development of depressive-like behaviors in mice with reactivated T. gondii. PMID- 26554726 TI - Reduction in 50-kHz call-numbers and suppression of tickling-associated positive affective behaviour after lesioning of the lateral hypothalamic parvafox nucleus in rats. AB - The parvafox nucleus is located ventrolaterally in the lateral hypothalamic area (LHA). Its core and shell are composed of neurons expressing the calcium-binding protein parvalbumin (PV) and the transcription factor Foxb1, respectively. Given the known functions of the LHA and that the parvafox nucleus receives afferents from the lateral orbitofrontal cortex and projects to the periaqueductal gray matter, a functional role of this entity in the expression of positive emotions has been postulated. The purpose of the present study was to ascertain whether the deletion of neurons in the parvafox nucleus influenced the tickling-induced 50-kHz calls, which are thought to reflect positive affective states, in rats. To this end, tickling of the animals (heterospecific play) was combined with intracerebral injections of the excitotoxin kainic acid into the parvafox nucleus. The most pronounced surgery-associated reduction in 50-kHz call-numbers was observed in the group of rats in which, on the basis of PV-immunoreactive cell counts in the parvafox nucleus, bilateral lesions had been successfully produced. Two other parameters that were implemented to quantify positive affective behaviour, namely, an approach towards and a following of the hand of the tickling experimenter, were likewise most markedly suppressed in the group of rats with bilaterally successful lesions. Furthermore, positive correlations were found between each of the investigated parameters. Our data afford evidence that the parvafox nucleus plays a role in the production of 50-kHz calls in rats, and, more generally, in the expression of positive emotions. PMID- 26554723 TI - Hard to swallow: Developmental biological insights into pediatric dysphagia. AB - Pediatric dysphagia-feeding and swallowing difficulties that begin at birth, last throughout childhood, and continue into maturity--is one of the most common, least understood complications in children with developmental disorders. We argue that a major cause of pediatric dysphagia is altered hindbrain patterning during pre-natal development. Such changes can compromise craniofacial structures including oropharyngeal muscles and skeletal elements as well as motor and sensory circuits necessary for normal feeding and swallowing. Animal models of developmental disorders that include pediatric dysphagia in their phenotypic spectrum can provide mechanistic insight into pathogenesis of feeding and swallowing difficulties. A fairly common human genetic developmental disorder, DiGeorge/22q11.2 Deletion Syndrome (22q11DS) includes a substantial incidence of pediatric dysphagia in its phenotypic spectrum. Infant mice carrying a parallel deletion to 22q11DS patients have feeding and swallowing difficulties that approximate those seen in pediatric dysphagia. Altered hindbrain patterning, craniofacial malformations, and changes in cranial nerve growth prefigure these difficulties. Thus, in addition to craniofacial and pharyngeal anomalies that arise independently of altered neural development, pediatric dysphagia may result from disrupted hindbrain patterning and its impact on peripheral and central neural circuit development critical for feeding and swallowing. The mechanisms that disrupt hindbrain patterning and circuitry may provide a foundation to develop novel therapeutic approaches for improved clinical management of pediatric dysphagia. PMID- 26554728 TI - Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. AB - Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis. PMID- 26554729 TI - Evaluation of the Ocular Tolerance of Three Tacrolimus Topical Pharmaceutical Preparations by Bovine Corneal Opacity and Permeability Test. AB - PURPOSE: Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated. MATERIAL AND METHODS: Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent junctions E-cadherin, VE-cadherin and zonula occludens-1 were examined and scored to evaluate and to confirm corneal disruption and irritation scores obtained with the BCOP method. RESULTS: Commercial brand ointment (Protopic(r)), topical compounded eye ointment (pharmacy elaboration) and tacrolimus suspension eye drops (elaborated from parenteral prograf(r)) were tested as potential ocular preparations to be used in clinics. Tacrolimus preparations hereby studied do not alter the opacity and permeability of the bovine cornea by more than three units, measured by the In Vitro Irritancy Score, neither affected the immunohistochemical parameters, composite score or transepithelial electrical resistance. CONCLUSIONS: Tacrolimus preparations studied can be safely applied as a topical ocular treatment. PMID- 26554730 TI - Thalassobius abyssi sp. nov., a marine bacterium isolated from cold-seep sediment. AB - A novel marine bacterial strain, designated JAMH 043T, was isolated from cold seep sediment in Sagami Bay, Japan. Cells were Gram-stain-negative, rod-shaped, non-motile and aerobic chemo-organotrophs. The isolate grew optimally at 25 degrees C, at pH 7.0-7.5 and with 3 % (w/v) NaCl. The major respiratory quinone was ubiquinone-10 (Q-10). The predominant fatty acid was C18 : 1omega7c. On the basis of 16S rRNA gene sequence analysis, the isolated strain was closely affiliated to members of the genus Thalassobius in the class Alphaproteobacteria, and 16S rRNA gene sequence similarity of the novel isolate with the type strain of its closest related species, Thalassobius aestuarii JC2049T, was 98.4 %. The DNA G+C content of the novel strain was 58.0 mol%. The hybridization values for DNA-DNA relatedness between strain JAMH 043T and reference strains belonging to the genus Thalassobius were less than 14.1 +/- 2.2 %. Based on differences in taxonomic characteristics, the isolated strain represents a novel species of the genus Thalassobius, for which the name Thalassobius abyssi sp. nov. is proposed. The type strain is JAMH 043T ( = JCM 30900T = DSM 100673T). PMID- 26554731 TI - HPV vaccination for MSM: Synthesis of the evidence and recommendations from the Quebec Immunization Committee. AB - Diseases associated with the human papilloma virus (HPV) are particularly common among men who have sex with men (MSM). Unlike heterosexual men, MSM do not benefit from the herd protection provided by the vaccination of girls. In this review, we synthesize the available evidence on HPV vaccination for MSM. We also present the recommendations of the Quebec Immunization Committee (CIQ) in this regard, which are: to provide targeted vaccination for MSM up to 26 years of age and in-school vaccination of preadolescent boys since this is the best approach to take to have a real impact on the burden related to HPV in the MSM population and to provide direct protection for all men. PMID- 26554732 TI - Development of prognostic model for predicting survival after retrograde placement of ureteral stent in advanced gastrointestinal cancer patients and its evaluation by decision curve analysis. AB - BACKGROUND: The aim of this study was to determine risk factors for survival after retrograde placement of ureteral stents and develop a prognostic model for advanced gastrointestinal tract (GIT: esophagus, stomach, colon and rectum) cancer patients. METHODS: We examined the clinical records of 122 patients who underwent retrograde placement of a ureteral stent against malignant extrinsic ureteral obstruction. A prediction model for survival after stenting was developed. We compared its clinical usefulness with our previous model based on the results from nephrostomy cases by decision curve analysis. RESULTS: Median follow-up period was 201 days (8-1490) and 97 deaths occurred. The 1-year survival rate in this cohort was 29%. Based on multivariate analysis, primary site of colon origin, absence of retroperitoneal lymph node metastasis and serum albumin >3g/dL were significantly associated with a prolonged survival time. To develop a prognostic model, we divided the patients into 3 risk groups of favorable: 0-1 factors (N.=53), intermediate: 2 risk factors (N.=54), and poor: 3 risk factors (N.=15). There were significant differences in the survival profiles of these 3 risk groups (P<0.0001). Decision curve analyses revealed that the current model has a superior net benefit than our previous model for most of the examined probabilities. CONCLUSIONS: We have developed a novel prognostic model for GIT cancer patients who were treated with retrograde placement of a ureteral stent. The current model should help urologists and medical oncologists to predict survival in cases of malignant extrinsic ureteral obstruction. PMID- 26554733 TI - Modality and dosing of acute renal replacement therapy. AB - Acute renal replacement therapy (ARRT) is today routinely applied in critically ill patients with acute kidney injury. Nevertheless, differently from other therapies in the acute care setting which have specific posology, duration of treatment, serum through and peak levels and clearly predetermined continuous or intermittent way of administration, ARRT may appear difficult to dose, prescribe, deliver and monitor. Additionally, current literature has provided controversial results about many aspects of ARRT administration. This review will focus on the definition of dialytic dose, extensively detailing different dimensions of ARRT delivery: as a matter of fact, the provision of a dialytic session to a critically ill patient should not be limited to the simplistic mathematical calculation of an exact dose. Adequacy of ARRT implies the concomitant consideration of more complex issues such as timing, modality and techniques of ARRT delivery, anticoagulation and substitution fluids choice, membrane selection, monitor accuracy, the role of fluid overload and other patients' comorbidities. The capacity of clinicians of considering all these aspects, adapting the different dimensions of dose to the actual patients' needs, might be the fundamental missing element in the pathway towards significant outcome improvements of critically ill AKI patients needing ARRT. PMID- 26554734 TI - Reduced Susceptibility to Xanthomonas citri in Transgenic Citrus Expressing the FLS2 Receptor From Nicotiana benthamiana. AB - Overexpression of plant pattern-recognition receptors by genetic engineering provides a novel approach to enhance plant immunity and broad-spectrum disease resistance. Citrus canker disease associated with Xanthomonas citri is one of the most important diseases damaging citrus production worldwide. In this study, we cloned the FLS2 gene from Nicotiana benthamiana cDNA and inserted it into the binary vector pBinPlus/ARS to transform Hamlin sweet orange and Carrizo citrange. Transgene presence was confirmed by polymerase chain reaction (PCR) and gene expression of NbFLS2 was compared by reverse transcription quantitative PCR. Reactive oxygen species (ROS) production in response to flg22Xcc was detected in transgenic Hamlin but not in nontransformed controls. Low or no ROS production was detected from nontransformed Hamlin seedlings challenged with flg22Xcc. Transgenic plants highly expressing NbFLS2 were selected and were evaluated for resistance to canker incited by X. citri 3213. Our results showed that the integration and expression of the NbFLS2 gene in citrus can increase canker resistance and defense-associated gene expression when challenged with X. citri. These results suggest that canker-susceptible Citrus genotypes lack strong basal defense induced by X. citri flagellin and the resistance of these genotypes can be enhanced by transgenic expression of the flagellin receptor from a resistant species. PMID- 26554735 TI - A Fungal Effector With Host Nuclear Localization and DNA-Binding Properties Is Required for Maize Anthracnose Development. AB - Plant pathogens have the capacity to manipulate the host immune system through the secretion of effectors. We identified 27 putative effector proteins encoded in the genome of the maize anthracnose pathogen Colletotrichum graminicola that are likely to target the host's nucleus, as they simultaneously contain sequence signatures for secretion and nuclear localization. We functionally characterized one protein, identified as CgEP1. This protein is synthesized during the early stages of disease development and is necessary for anthracnose development in maize leaves, stems, and roots. Genetic, molecular, and biochemical studies confirmed that this effector targets the host's nucleus and defines a novel class of double-stranded DNA-binding protein. We show that CgEP1 arose from a gene duplication in an ancestor of a lineage of monocot-infecting Colletotrichum spp. and has undergone an intense evolution process, with evidence for episodes of positive selection. We detected CgEP1 homologs in several species of a grass infecting lineage of Colletotrichum spp., suggesting that its function may be conserved across a large number of anthracnose pathogens. Our results demonstrate that effectors targeted to the host nucleus may be key elements for disease development and aid in the understanding of the genetic basis of anthracnose development in maize plants. PMID- 26554736 TI - Pseudomonas syringae pv. tomato OxyR Is Required for Virulence in Tomato and Arabidopsis. AB - Reactive oxygen species (ROS) have been shown to have a crucial role in plant defense responses and signaling pathways. In addition, ROS also have direct toxicity against pathogens. However, the molecular mechanisms of plant ROS in the direct effects against pathogens is still unclear. To investigate the function of plant ROS in the interactions of plant and bacterial pathogens, we focused on oxyR, encoding an oxidative stress-regulated transcription factor in Pseudomonas syringae pv. tomato DC3000 (DC3000), and generated an DeltaoxyR mutant. The DC3000 DeltaoxyR mutant showed high sensitivity to oxidative stress in comparison with wild type and the complemented line. The host plants of DC3000, including tomato and Arabidopsis inoculated with the DeltaoxyR mutant, clearly showed reduced disease symptoms as well as reduced bacterial populations. Expression profiles of DC3000 genes revealed that OxyR could regulate the expression of genes encoding ROS-detoxifying enzymes, including catalases (KatB and KatG), in response to ROS. We also demonstrated that the expression of katB could be regulated by OxyR during the infection of DC3000 in Arabidopsis. These results suggest that OxyR has an important role in the virulence of DC3000 by regulating the expression of genes related to oxidative stress. PMID- 26554737 TI - A tertiary experience of ileal-ureter substitution: Contemporary indications and outcomes. AB - OBJECTIVE: Complex ureteric stricture disease in contemporary practice is typically related to prior pelvic surgery, radiotherapy, or complicated, repeated retrograde stone surgery, although outcomes in this group have not been well studied. The aim of this study was to report medium-term outcomes with ileal ureter substitution for complex ureteric stricture disease. MATERIALS AND METHODS: All patients who had undergone ureteric reconstructive surgery using small bowel over a 5 year period between 2010 and 2015 were identified from the theatre database and their case notes reviewed. Data were collected on aetiology of ureteric stricture, prior surgery or radiotherapy, baseline renal function and comorbidity. Postoperative complications were recorded using the Clavien-Dindo classification, and overall outcome and need for further intervention were documented. RESULTS: Nine patients underwent ileal-ureter substitution for complex ureteric stricture disease over this period, with four having bilateral ileal interpositions. Median age was 48 years (38-62 years) with a median follow up of 17 months (1-40 months). Simple untailored ileal segments and refluxing anastomoses were used in all cases. One case of anastomotic leak and restricture required reintervention, but all others had favourable outcomes with no stricture and no requirement for further intervention. Two patients reported recurrent cystitis following surgery but there was no deterioration in renal function in any patient, with no metabolic complications reported. CONCLUSION: Ileal-ureter substitution surgery is a valuable option for selected patients with complex, difficult-to-treat ureteric defects that cannot be bridged by other methods. Simple onlay techniques do not seem to affect renal or metabolic function. Avoiding the extra complexity of tailored and tunnelled anastomoses may reduce the potential morbidity and reintervention rate in patients with challenging surgical fields. PMID- 26554738 TI - First Detection of the -27 (A > G) (HBB: c.-77A > G) Mutation of the beta-Globin Gene in a Chinese Family. AB - We present the first description of a novel beta-thalassemia (beta-thal) mutation in a Chinese family. This mutation is located at -27 of the TATA box in the promoter of the beta-globin gene (HBB: c.-77A > G) and is likely associated with a phenotype of beta(+)-thalassemia (beta(+)-thal). PMID- 26554739 TI - Cost-effectiveness analysis of genotyping for HLA-B*5801 and an enhanced safety program in gout patients starting allopurinol in Singapore. AB - AIMS: Allopurinol is an efficacious urate-lowering therapy (ULT), but is associated with rare serious adverse drug reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with higher risk among HLA-B*5801 carriers. We assessed the cost-effectiveness of HLA-B*5801 testing, an enhanced safety program or strategies with both components. METHODS: The analysis adopted a health systems perspective and considered Singaporean patients with chronic gout, over a lifetime horizon, using allopurinol or probenecid. The model incorporated SJS/TEN and gout treatment outcomes, allele frequencies, drug prices and other medical costs. RESULTS: Based on cost-effectiveness threshold of US$50,000 per quality-adjusted life year, HLA-B*5801-guided ULT selection or enhanced safety program was not cost effective. Avoidance of ULTs was the least preferred strategy as uncontrolled gout leads to lower quality-adjusted life years and higher costs. CONCLUSION: The analysis underscores the need for biomarkers with higher positive predictive value for SJS/TEN, less expensive genetic tests or safety programs, or more effective gout drugs. . PMID- 26554740 TI - Cleansing of Body and Spirit. PMID- 26554741 TI - 10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity. AB - In the present study, we investigated the roles and molecular mechanism of 10 gingerol, a phenolic compound isolated from Zingiber officinale, in regulating cell proliferation and invasion of MDA-MB-231 breast cancer cells. 10-gingerol treatment inhibited cell proliferation through downregulation of cell cycle regulatory proteins such as cyclin-dependent kinases and cyclins, and subsequent induction of G1 phase arrest. In addition, 10-gingerol treatment blocked cell invasion in response to mitogenic stimulation. These antitumor activities of 10 gingerol were mediated through inactivation of Akt and p38MAPK activity, and suppression of epidermal growth factor receptor expression. Collectively, these findings demonstrate the pharmacological roles of 10-gingerol in regulating breast cancer cell growth and progression, and suggest further evaluation and development as a potential therapeutic agent for the prevention and treatment of breast cancer. PMID- 26554742 TI - Selection of an actinobacteria mixed culture for chlordane remediation. Pesticide effects on microbial morphology and bioemulsifier production. AB - Chlordane bioremediation using actinobacteria mixed culture is an attractive clean-up technique. Their ability to produce bioemulsifiers could increase the bioavailability of this pesticide. In order to select a defined actinobacteria mixed culture for chlordane remediation, compatibility assays were performed among six Streptomyces strains. The strains did not show growth inhibition, and they were assayed for chlordane removal, either as pure or as mixed cultures. In pure cultures, all of the strains showed specific dechlorination activity (1.42 24.20 EU mg(-1)) and chlordane removal abilities (91.3-95.5%). The specific dechlorination activity was mainly improved with cultures of three or four microorganisms. The mixed culture consisting of Streptomyces sp. A2-A5-A13 was selected. Their ability to produce bioemulsifiers in the presence of glucose or chlordane was tested, but no significant differences were observed (p > 0.05). However, the stability of the emulsions formed was linked to the carbon source used. Only in chlordane presence the emulsions retained 100% of their initial height. Finally, the selected consortium showed a high degree of sporulation in the pesticide presence. This is the first study on the effects that chlordane exerts on microbe morphology and emulsifier production for a defined mixed culture of Streptomyces with ability to remediate the pesticide. PMID- 26554743 TI - Insight of In Vitro Small-Interfering RNA Release From Chitosan Nanoparticles Under Enzymolysis With Forster Resonance Energy Transfer Analysis. AB - Small-interfering RNA (siRNA)-mediated gene silencing with the aid of chitosan (CS)-based carriers has shown efficient and reliable outcome in vitro, but the gene silencing efficiency in vivo is still limited. It is of great importance to balance the protection and release of siRNA from nanoparticles (NPs) so as to achieve high efficiency. However, siRNA release profile from CS/siRNA NPs has been rarely concerned. Here, Forster resonance energy transfer technique was adopted for in vitro investigation of siRNA release from CS NPs in lysozyme contained buffer. The results clearly showed that siRNA molecules experienced a fast and short release phase under lysozyme competition to both CS and siRNA, and then a slow and long release under lysozyme degradation on CS. Moreover, lysozyme competition played more important role than enzymolysis on trigging siRNA release. This preliminary study of siRNA release is the first step to get insight of in vivo siRNA release mechanism from CS/siRNA NPs, which will be helpful to adjust the design of CS/siRNA NPs for balancing the protection and release of siRNA molecules. PMID- 26554744 TI - A Reproducible Computerized Method for Quantitation of Capillary Density using Nailfold Capillaroscopy. AB - Capillaroscopy is a non-invasive, efficient, relatively inexpensive and easy to learn methodology for directly visualizing the microcirculation. The capillaroscopy technique can provide insight into a patient's microvascular health, leading to a variety of potentially valuable dermatologic, ophthalmologic, rheumatologic and cardiovascular clinical applications. In addition, tumor growth may be dependent on angiogenesis, which can be quantitated by measuring microvessel density within the tumor. However, there is currently little to no standardization of techniques, and only one publication to date reports the reliability of a currently available, complex computer based algorithms for quantitating capillaroscopy data.(1) This paper describes a new, simpler, reliable, standardized capillary counting algorithm for quantitating nailfold capillaroscopy data. A simple, reproducible computerized capillaroscopy algorithm such as this would facilitate more widespread use of the technique among researchers and clinicians. Many researchers currently analyze capillaroscopy images by hand, promoting user fatigue and subjectivity of the results. This paper describes a novel, easy-to-use automated image processing algorithm in addition to a reproducible, semi-automated counting algorithm. This algorithm enables analysis of images in minutes while reducing subjectivity; only a minimal amount of training time (in our experience, less than 1 hr) is needed to learn the technique. PMID- 26554745 TI - Analysis of Complete Remission in Systemic Lupus Erythematosus Patients Over a 32 Year Period. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by an unpredictable and fluctuating course. Although various methods have been developed to measure disease activity, there is still a lack of consensus about the optimal criteria for SLE remission. The principal aim of our study was to identify the number of lupus patients achieving a complete remission (implying that for 3 years there were no clinical or serologic features and no treatment with steroids and immunosuppressive drugs) in a single cohort of patients followed for a period of up to 32 years. In addition, we have identified patients in clinical but not serologic remission (known as serologically active, clinically quiescent disease [SACQ]) and vice versa. We were particularly interested to determine the factors associated with complete remission. METHODS: Eligible patients were followed up in the University College Hospital Lupus cohort from January 1978 until December 2010 for a period of at least 3 years. Complete remission was defined as a period of at least 3 years with clinical inactivity (British Isles Lupus Assessment Group scores of C, D, or E only) and laboratory remission (no antibodies to double-stranded DNA and normal complement C3 levels), and being off-treatment with corticosteroids and immunosuppressants. Antimalarial and nonsteroidal antiinflammatory drugs were allowed. RESULTS: Of 624 lupus patients at our hospital, a total of 532 patients met the strict inclusion criteria for the study. Of these 532 patients, 77 patients (14.5%) achieved complete remission for at least 3 years, and 23 (4.3%) achieved complete remission for a minimum period of 10 years. Ten of these 77 patients were subsequently lost to followup, and, interestingly, flares occurred subsequently in 15 of the 67 remaining patients (22.4%). Three patients relapsed after the tenth year of remission. Forty-five patients (8.5%) fulfilled the requirement for SACQ, and 66 patients (12.4%) achieved only serologic remission. CONCLUSION: Our study indicated that 14.5% of lupus patients achieved a complete remission for 3 years. However, flares may continue to occur beyond 10 years of remission. Long term followup of SLE is therefore mandatory. PMID- 26554746 TI - Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis: reply. PMID- 26554747 TI - Regulation of skeletal muscle capillary growth in exercise and disease. AB - Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient, and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients, and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is coordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic, and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout and short-term and long-term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations. PMID- 26554748 TI - A Highly Reactive Seven-Coordinate Osmium(V) Oxo Complex: [Os(V)(O)(qpy)(pic)Cl](2+). AB - Seven-coordinate ruthenium oxo species have been proposed as active intermediates in catalytic water oxidation by a number of highly active ruthenium catalysts, however such species have yet to be isolated. Reported herein is the first example of a seven-coordinate group 8 metal-oxo species, [Os(V)(O)(qpy)(pic)Cl](2+) (qpy = 2,2':6',2'':6'',2'''-quaterpyridine, pic = 4 picoline). The X-ray crystal structure of this complex shows that it has a distorted pentagonal bipyramidal geometry with an Os=O distance of 1.7375 A. This oxo species undergoes facile O-atom and H-atom-transfer reactions with various organic substrates. Notably it can abstract H atoms from alkylaromatics with C-H bond dissociation energy as high as 90 kcal mol(-1). This work suggests that highly active oxidants may be designed based on group 8 seven-coordinate metal oxo species. PMID- 26554749 TI - Intrapartum Synthetic Oxytocin and Its Effects on Maternal Well-Being at 2 Months Postpartum. AB - BACKGROUND: Synthetic oxytocin (synOT) is commonly used in labor management to induce and augment labor, and to prevent postpartum hemorrhage. However, its long term consequences for maternal health and behavior are largely understudied. We examined the relationship between synOT and maternal oxytocin levels, breastfeeding, and maternal mental health at 2 months postpartum. METHODS: Women were recruited during pregnancy or within 48 hours of giving birth through obstetric practices and hospitals. A total of 386 women were visited in their homes at 2 months postpartum, where they completed questionnaires assessing breastfeeding, depression, anxiety, posttraumatic stress, and somatization. Oxytocin levels were obtained from blood samples and synOT dosage information was gathered from hospital charts. RESULTS: Intrapartum synOT dose was positively correlated with endogenous oxytocin levels at 2 months postpartum. Women who were exclusively breastfeeding at 2 months postpartum had received significantly less synOT compared with their nonexclusively breastfeeding counterparts. Higher synOT dose was associated with greater depressive, anxious, and somatization symptoms. SynOT dose was not associated with perinatal posttraumatic stress. CONCLUSIONS: The widespread use of synOT in managed labor warrants caution, as the influence of synOT on a new mother's well-being is evident at 2 months postpartum. PMID- 26554750 TI - Prenatal triptan exposure and parent-reported early childhood neurodevelopmental outcomes: an application of propensity score calibration to adjust for unmeasured confounding by migraine severity. AB - PURPOSE: Triptan medications are serotonin agonists used to treat migraine, a chronic pain condition highly prevalent in women of reproductive age. Data on the safety of triptans during pregnancy are scant. We sought to quantify the association of prenatal triptan exposure on neurodevelopment in 3-year-old children. METHODS: Using data from the Norwegian Mother and Child Cohort Study, we used propensity score matching to examine associations between prenatal triptan exposure and psychomotor function, communication, and temperament. We used an external validation study to perform propensity calibration to adjust effect estimates for confounders unmeasured in the main study (migraine severity, type, and maternal attitudes towards medication use). RESULTS: We identified 4204 women who reported migraine headache at baseline, of which 375 (8.9%) reported using a triptan greater than or equal to once during pregnancy. Children with prenatal triptan exposure had 1.37-fold greater unadjusted odds of fine motor problems (95% confidence interval (CI): 1.06-1.77), which decreased after propensity score matching (odds ratio (OR): 1.29, 95%CI 0.97-1.73) and was further attenuated after calibration (OR: 1.25, 95%CI 0.89-1.74). We observed no increased risk for gross motor or communication problems, and no differences in temperament. Adjustment for migraine severity using propensity score calibration had a moderate impact on effect estimates, with percent changes ranging from 2.4% to 50%. CONCLUSIONS: Prenatal triptan exposure was not associated with psychomotor function, communication problems, or temperament in 3-year-old children. Adjustment for migraine severity reduced effect estimates and should be considered in future studies of the safety of triptans during pregnancy. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26554751 TI - Patterns of recurrence and survival after abdominal versus laparoscopic/robotic radical hysterectomy in patients with early cervical cancer. AB - AIM: This study investigates the pattern of disease recurrence and identifies the clinicopathologic prognostic factors for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB and IIA cervical carcinoma treated with laparoscopic/robotic radical hysterectomy (LRH/RRH). METHODS: We conducted a retrospective analysis of 128 patients with FIGO stage IB and IIA cervical cancer. Preoperative examination did not uncover definitive evidence of parametrial invasion or lymph node metastasis in any of the patients; therefore, all patients underwent LRH/RRH with retroperitoneal lymphadenectomy between April 2006 and December 2013. Sites of disease recurrence and all possible clinicopathologic factors related to the risk of disease recurrence were determined. RESULTS: Multivariate analysis demonstrated that laparoscopic intracorporeal colpotomy (P < 0.041, odds ratio 7.038, 95% confidence interval 1.059-15.183) represented a strong prognostic factor related to disease recurrence. We categorized the minimally invasive surgery group into LRH through vaginal colpotomy (LRH-VC; 79 patients) and LRH/RRH through intracorporeal colpotomy (LRH/RRH-IC; 49 patients) according to the colpotomic approaches. Disease recurrence was higher in the LRH/RRH-IC group than in the LRH-VC group (16.3% vs 5.1%, P = 0.057), with five patients in the LRH/RRH-IC group experiencing intraperitoneal spreads. CONCLUSIONS: Total laparoscopic/robotic intracorporeal colpotomy under CO2 pneumoperitoneum may carry a risk of positive vaginal cuff margin, as well as intraperitoneal tumor spreads in patients with early-stage cervical cancer treated with LRH/RRH. PMID- 26554753 TI - A cross-biome synthesis of soil respiration and its determinants under simulated precipitation changes. AB - Soil respiration (Rs) is the second-largest terrestrial carbon (C) flux. Although Rs has been extensively studied across a broad range of biomes, there is surprisingly little consensus on how the spatiotemporal patterns of Rs will be altered in a warming climate with changing precipitation regimes. Here, we present a global synthesis Rs data from studies that have manipulated precipitation in the field by collating studies from 113 increased precipitation treatments, 91 decreased precipitation treatments, and 14 prolonged drought treatments. Our meta-analysis indicated that when the increased precipitation treatments were normalized to 28% above the ambient level, the soil moisture, Rs, and the temperature sensitivity (Q10) values increased by an average of 17%, 16%, and 6%, respectively, and the soil temperature decreased by -1.3%. The greatest increases in Rs and Q10 were observed in arid areas, and the stimulation rates decreased with increases in climate humidity. When the decreased precipitation treatments were normalized to 28% below the ambient level, the soil moisture and Rs values decreased by an average of -14% and -17%, respectively, and the soil temperature and Q10 values were not altered. The reductions in soil moisture tended to be greater in more humid areas. Prolonged drought without alterations in the amount of precipitation reduced the soil moisture and Rs by -12% and -6%, respectively, but did not alter Q10. Overall, our synthesis suggests that soil moisture and Rs tend to be more sensitive to increased precipitation in more arid areas and more responsive to decreased precipitation in more humid areas. The responses of Rs and Q10 were predominantly driven by precipitation-induced changes in the soil moisture, whereas changes in the soil temperature had limited impacts. Finally, our synthesis of prolonged drought experiments also emphasizes the importance of the timing and frequency of precipitation events on ecosystem C cycles. Given these findings, we urge future studies to focus on manipulating the frequency, intensity, and seasonality of precipitation with an aim to improving our ability to predict and model feedback between Rs and climate change. PMID- 26554752 TI - Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. AB - OBJECTIVE: To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles in patients with periodontitis, patients with RA, and controls. METHODS: Anti-RgpB IgG was measured by enzyme-linked immunosorbent assay in 65 periodontitis patients and 59 controls without periodontitis, and in 1,974 RA patients and 377 controls without RA from the Swedish population-based case-control Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Autoantibody status, smoking habits, and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using the Mann Whitney U test. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs) for the association of anti RgpB IgG with different subsets of RA patients. RESULTS: Anti-RgpB antibody levels were significantly elevated in periodontitis patients compared to controls without periodontitis, in RA patients compared to controls without RA, and in ACPA-positive RA patients compared to ACPA-negative RA patients. There was a significant association between anti-RgpB IgG and RA (OR 2.96 [95% CI 2.00, 4.37]), which was even stronger than the association between smoking and RA (OR 1.37 [95% CI 1.07, 1.74]), and in ACPA-positive RA there were interactions between anti-RgpB antibodies and both smoking and the HLA-DRB1 SE. CONCLUSION: Our study suggests that the previously reported link between periodontitis and RA could be accounted for by P gingivalis infection, and we conclude that P gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RA patients. PMID- 26554755 TI - Lymphopenia in Patients with Single-ventricle Heart Disease after the Fontan Operation. AB - BACKGROUND: Lymphopenia is common in patients with Fontan circulation and no history of protein-losing enteropathy, but this phenomenon has not been significantly described in the literature. METHODS: We retrospectively identified patients with Fontan circulation who underwent catheterization between January 2003 and January 2013 at our center. Patients who had complete blood count with differential drawn within 12 months of the catheterization were included. Patients were excluded if complete blood count with differential was drawn in setting of possible infection or if there was history of protein-losing enteropathy (PLE). Possible associations between patient characteristics and absolute lymphocyte count (ALC) were examined. RESULTS: Fifteen patients were included. The median age at catheterization was 10.2 years (3.8-26.9) and median time from Fontan operation was 6.5 years (0.7-22.1). Twelve (80%) patients had undergone extracardiac Fontan and 9 (60%) had fenestration placed. The median time between complete blood count with differential and catheterization was 2 days (0-346). The median inferior vena cava (IVC) pressure was 13 mm Hg (7-20). The median ALC was 1.5 * 10(3) /MUL (0.8-4.5). Four patients (26.7%) met criteria for lymphopenia with ALC < lower limit of normal and 7 (46.7%) patients had an ALC <= lower limit of normal. ALC was not associated with any hemodynamic variables but was associated with platelet count (rho = 0.5, P = .04), total white blood cell count (rho = 0.8, P <= .001), and absolute monocyte count (0.7, P = .002). CONCLUSIONS: In a cohort of patients with Fontan circulation and no history of protein-losing enteropathy who underwent catheterization, lymphopenia was common and positively associated with low platelet count. Thrombocytopenia has been shown to correlate with the degree of hepatic fibrosis in those with Fontan and, thus, hepatic fibrosis may underlie lymphopenia in these patients. PMID- 26554754 TI - Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma. AB - BACKGROUND: The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. METHODS: The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. RESULTS: In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. CONCLUSIONS: The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. PMID- 26554756 TI - Disease burden of congenital cytomegalovirus infection at school entry age: study design, participation rate and birth prevalence. AB - Congenital cytomegalovirus infection (cCMV) may lead to symptoms at birth and long-term consequences. We present a nationwide, retrospective cohort study on the outcome of cCMV up to age 6 years. For this study we identified cCMV, using polymerase chain reaction, by analysing dried blood spots, which are taken shortly after birth for neonatal screening. The group of children with cCMV were compared to a group of children who were cCMV negative at birth. Data were collected about their health and development up to age 6 years. Parents of 73 693 children were invited to participate, and 32 486 (44.1%) gave informed consent for testing of their child's dried blood spot for CMV. Of the 31 484 dried blood spots tested, 156 (0.5%) were positive for cCMV. Of these, four (2.6%) children had been diagnosed with cCMV prior to this study. This unique retrospective nationwide study permits the estimation of long-term sequelae of cCMV up to the age of 6 years. The birth prevalence of cCMV in this study was 0.5%, which is in line with prior estimates. Most (97.4%) children with cCMV had not been diagnosed earlier, indicating under-diagnosis of cCMV. PMID- 26554757 TI - Caffeine intake is related to successful weight loss maintenance. AB - The effect of caffeine intake on weight loss maintenance has not been examined in humans. We compared the daily consumption of coffee and caffeinated beverages between 494 weight loss maintainers and 2129 individuals from the general population controlling for sociodemographic variables, body mass index and physical activity level. Weight loss maintainers reported to consume significantly more cups of coffee and caffeinated beverages compared with the participants in the general population sample. Thus, consumption of caffeinated beverages might support weight loss maintenance. Further studies should investigate possible mechanisms. PMID- 26554759 TI - Exploring the Nanoscale: Fifteen Years of Tip-Enhanced Raman Spectroscopy. AB - Spectroscopic methods with high spatial resolution are essential to understand the physical and chemical properties of nanoscale materials including biological and chemical materials. Tip-enhanced Raman spectroscopy (TERS) is a combination of surface-enhanced Raman spectroscopy (SERS) and scanning probe microscopy (SPM), which can provide high-resolution topographic and spectral information simultaneously below the diffraction limit of light. Even examples of sub nanometer resolution have been demonstrated. This review intends to give an introduction to TERS, focusing on its basic principle and the experimental setup, the strengths followed by recent applications, developments, and perspectives in this field. PMID- 26554758 TI - The effect of moderate alcohol consumption on biomarkers of inflammation and hemostatic factors in postmenopausal women. AB - BACKGROUND/OBJECTIVES: Inflammation and hemostasis contribute to the etiology of cardiovascular disease. We previously demonstrated that moderate alcohol consumption (1-2 drinks/day) may decrease risk for cardiovascular disease because of an improved lipid profile. In addition to these beneficial changes, the alcohol-mediated reduction in risk may be through its effect on inflammation and hemostasis. The objective of the study was to evaluate the effect of moderate alcohol consumption on biomarkers of inflammation and hemostasis in postmenopausal women. SUBJECTS/METHODS: As part of a controlled diet study, 53 postmenopausal women each consumed a weight-maintaining diet plus 0, 15 and 30 g/day of alcohol for 8 weeks, in a randomized crossover design. The controlled diet contained 15%, 53% and 32% of energy from protein, carbohydrate and fat, respectively. RESULTS: Soluble intercellular adhesion molecule-1 decreased by 5% (P<0.05) with consumption of both 15 and 30 g of alcohol. Fibrinogen concentrations decreased by 4% and 6% (P<0.05) after consumption of 15 and 30 g alcohol, respectively. Fibrin D-dimer decreased by 24% (P<0.05) after consumption of 30 g of alcohol. Plasminogen activator inhibitor-1 (PAI-1) concentrations were increased 27 and 54% (P<0.05) after consumption of 15 and 30 g of alcohol. Plasma high-sensitivity C-reactive protein, interleukin-6 and factor VII coagulant activity did not change with alcohol consumption. CONCLUSIONS: These data suggest that moderate alcohol consumption may have beneficial effects on inflammation and hemostasis in postmenopausal women, and this may be somewhat mitigated by an increase in PAI-1. PMID- 26554760 TI - Bioinspired Hydroxyapatite/Poly(methyl methacrylate) Composite with a Nacre Mimetic Architecture by a Bidirectional Freezing Method. AB - Using a bidirectional freezing technique, combined with uniaxial pressing and in situ polymerization, "nacre-mimetic" hydroxyapatite/poly(methyl methacrylate) (PMMA) composites are developed by processing large-scale aligned lamellar ceramic scaffolds. Structural and mechanical characterization shows "brick-and mortar" structures, akin to nacre, with interesting combinations of strength, stiffness, and work of fracture, which provide a pathway to making strong and tough lightweight materials. PMID- 26554761 TI - Mitogen-Activated Protein Kinase Kinase 4 Gene Polymorphism and Cancer Risk. AB - A number of epidemiological studies have assessed the association of -1304T > G polymorphism in the MKK4 gene and risk of cancer, but the results lack of statistical power due to the limited subjects used in these studies. This study was devised to identify the genetic effects of the -1304T > G polymorphism on cancer risk in a large meta-analysis.Eligible studies were identified by searching both Chinese and English databases. General as well as subgroup analyses were performed for 8 independent case-control publications with a total of 4623 cases and 5256 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association.Overall, this meta-analysis showed that the association between the -1304T > G polymorphism and cancer risk was statistically significant (GG vs TT: OR = 0.63, 95% CI, 0.52-0.75; GG + TG vs TT: OR = 0.85, 95% CI, 0.79-0.91; GG vs TG + TT: OR = 0.67, 95% CI, 0.56-0.80; G vs T: OR = 0.82, 95% CI, 0.77-0.88; TG vs TT: OR = 0.86, 95% CI, 0.79-0.93).Our meta-analysis reveals that the presence of the -1304T > G polymorphism is likely to decrease risk of cancer. Future larger studies are necessary to validate the current finding. PMID- 26554762 TI - Predictive Value of Serum miR-10b, miR-29c, and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening. AB - Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. The high mortality of ESCC is mainly due to late diagnosis. Current detection methods have their own weakness, including high costs and invasive procedures. MicroRNA assays are shown to have great potential to be accurate and noninvasive methods for ESCC screening. In this study, we selected 3 microRNAs, miR-10b, miR-29c, and miR-205, to assess their diagnostic value in ESCC screening. Fifty ESCC patients and 50 healthy controls are recruited in our study. Blood samples are collected from the total 100 participants. MicroRNAs were extracted from serum and quantified by qRT-PCR, which their relative expressions were normalized by internal control, U6 snRNA. Statistical analyses were conducted to compare microRNAs level as well as other clinical characteristics between 2 groups. The levels of serum miR-29c and miR-205 were significantly downregulated in ESCC patients compared with healthy volunteers. In contrast, ESCC patients appeared to have a higher level of miR-10b than healthy controls. ROC curve analyses revealed that the AUC value for miR-10b, miR-29c, and miR-205 were 0.85 (95% CI: 0.79-0.93; sensitivity = 76%; specificity = 84%), 0.72 (95% CI: 0.62-0.82; sensitivity = 68%; specificity = 68%), and 0.72 (95% CI: 0.62-0.83; sensitivity = 70%; specificity = 64%), respectively, suggesting that miR-10b, miR-29c, and miR-205 have great potential to be noninvasive screening tools for ESCC detection. PMID- 26554764 TI - Application of Optical Coherence Tomography and Contrast Sensitivity Test for Observing Fundus Changes of Patients With Pregnancy-Induced Hypertension Syndrome. AB - This study was aimed to investigate the fundus changes of patients with pregnancy induced hypertension syndrome (PIHS) using optical coherence tomography (OCT) technology and contrast sensitivity (CS) tests.Ninety-eight patients with PIHS underwent routine eye examinations including vision correction, fundus examination, OCT, and CS tests. The CS test was performed at low, medium, and high frequency, respectively. Moreover, the difference in CS tests between 2 groups was analyzed by independent-samples T test. The Kruskal-Wallis rank sum test and linear regression model were used to detect the correlation of OCT with CS, respectively. Meanwhile Satterthwaite approximate T test was adopted for pairwise comparisons after nonparametric analysis of variance.The OCT test revealed that 56.76% of the examined eyes showed shallow retinal detachment in the macula lutea and around the optic disk. The differences in CS at each spatial frequency between the case and control group were statistically significant (P < 0.01). Besides, OCT manifestations were associated with CS at each spacial frequency including 1.5, 3, 6, 12, and 18 frequency (P < 0.01). And patients with abnormal manifestations of OCT showed lower CS at each spacial frequency than those without abnormal OCT manifestations. What's more the OCT manifestation 1 showed the greatest impact on CS at each spacial frequency.The results showed that abnormal OCT manifestations were correlated with CS in PIHS. OCT and CS tests might be valuable methods in observing fundus changes for PIHS patients. PMID- 26554763 TI - Which Biomarker is the Best for Predicting Mortality in Incident Peritoneal Dialysis Patients: NT-ProBNP, Cardiac TnT, or hsCRP?: A Prospective Observational Study. AB - Although numerous previous studies have explored various biomarkers for their ability to predict mortality in end-stage renal disease (ESRD) patients, these studies have been limited by retrospective analyses, mostly prevalent dialysis patients, and the measurement of only 1 or 2 biomarkers. This prospective study was aimed to evaluate the association between 3 biomarkers and mortality in incident 335 ESRD patients starting continuous ambulatory peritoneal dialysis (CAPD) in Korea. According to the baseline NT-proBNP, cTnT, and hsCRP levels, the patients were stratified into tertiles, and cardiovascular (CV) and all-cause mortalities were compared. Additionally, time-dependent ROC curves were constructed, and the net reclassification index (NRI) and integrated discrimination improvement (IDI) of the models with various biomarkers were calculated. We found the upper tertile of NT-proBNP was significantly associated with increased risk of both CV and all-cause mortalities. However, the upper tertile of hsCRP was significantly related only to the high risk of all-cause mortality even after adjustment for age, sex, and white blood cell counts. Moreover, NT-proBNP had the highest predictive power for CV mortality, whereas hsCRP was the best prognostic marker for all-cause mortality among these biomarkers. In conclusions, NT-proBNP is a more significant prognostic factor for CV mortality than cTnT and hsCRP, whereas hsCRP is a more significant predictor than NT-proBNP and cTnT for all-cause mortality in incident peritoneal dialysis patients. PMID- 26554765 TI - Surgical Therapy of Cervical Spine Fracture in Patients With Ankylosing Spondylitis. AB - The present study aimed to explore surgical treatments and assess the effects based on the features of cervical spine fracture in patients with ankylosing spondylitis (AS) and to summarize the experiences in perioperative management. Retrospective analysis was performed in 25 AS patients with cervical spine fracture treated in our hospital from January 2011 to December 2013. The patients were divided according to fracture segments, including 4 cases at C4 to C5, 8 cases at C5 to C6, and 13 cases at C6 to C7. Among them, 12 belonged to I type, 5 to II type, and 8 to III type based on the improved classification method for AS cervical spine fracture. The Subaxial Cervical Spine Injury Classification score for these patients was 7.2 +/- 1.3, and the assessment of their neurological function states showed 6 patients (24%) were in American Spinal Injury Association (ASIA) A grade, 1 (4%) in ASIA B grade, 3 (12%) in ASIA C grade, 12 (48%) in ASIA D grade, and 3 (12%) in ASIA E grade. Surgical methods contained simple anterior approach alone, posterior approach alone, and combined posterior anterior or anterior-posterior approach. The average duration of patients' hospital stay was 38.6 +/- 37.6, and the first surgical methods were as follows: anterior approach alone on 6 cases, posterior surgery alone on 9 cases, and combined posterior-anterior or anterior-posterior approach on 10 patients. The median segments of fixation and fusion were 4.1 +/- 1.4 sections. Thirteen patients developed complications. During 2 to 36 months of postoperative follow up, 1 patient died of respiratory failure caused by pulmonary infections 2 months after leaving hospital. At the end of the follow-up, bone graft fusion was achieved in the rest of patients, and obvious looseness or migration of internal fixation was not observed. In addition, the preoperative neurological injury in 12 patients (54.5%) was also alleviated in different levels. AS cervical spine fracture, an unstable fracture, should be treated with operation, and satisfactory effects will be achieved after the individualized surgical treatment according to the improved classification method for AS cervical spine fracture. PMID- 26554766 TI - Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis. AB - The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers beta-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP ( 64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects. PMID- 26554767 TI - Case Reports on the Differentiation of Malignant and Benign Intratracheal Lesions by 18F-FDG PET/CT. AB - Malignant tracheal tumors (primary and secondary) are rare and benign tumors of the tracheobronchial tree are also rare. Few reports have been issued on the F fluorodeoxyglucose (F-FDG) positron emission tomography (PET) findings of tracheal tumors or benign nontumorous tracheal lesions, which have been mainly studied by computed tomography (CT). The author reports 2 cases of intratracheal lesions with quite different F-FDG PET/CT findings. The first case was of a 73 year-old woman with colon cancer treated by hemicolectomy and subsequent adjuvant chemotherapy. Follow-up F-FDG PET/CT after 6 years revealed a hypermetabolic fungating mass (SUVmax: 5.8) in the distal trachea and biopsy confirmed intratracheal metastasis. The second case involved a 61-year-old man with tongue cancer who underwent mouth floor mass excision and right supraomohyoid neck dissection with submental flap reconstruction. Tracheal lesion was incidentally found during a F-FDG PET/CT follow-up study conducted 1 year later. A benign intratracheal condition with low FDG uptake (SUVmax: 1.2) and the lesion was not visualized by neck CT 4 months later. F-FDG PET/CT uptake was helpful in differentiating benign and malignant intratracheal lesions. PMID- 26554768 TI - New Trends in Acute Management of Colonic Diverticular Bleeding: A Systematic Review. AB - Colonic diverticular disease is the most common cause of lower gastrointestinal bleeding. In the past, this condition was usually managed with urgent colectomy. Recently, the development of endoscopy and interventional radiology has led to a change in the management of colonic diverticular bleeding.The aim of this systematic review is to define the best treatment for colonic diverticular bleeding.A systematic bibliographic research was performed on the online databases for studies (randomized controlled trials [RCTs], observational trials, case series, and case reports) published between 2005 and 2014, concerning patients admitted with a diagnosis of diverticular bleeding according to the PRISMA methodology.The outcomes of interest were: diagnosis of diverticulosis as source of bleeding; incidence of self-limiting diverticular bleeding; management of non self-limiting bleeding (endoscopy, angiography, surgery); and recurrent diverticular bleeding.Fourteen studies were retrieved for analysis. No RCTs were found. Eleven non-randomized clinical controlled trials (NRCCTs) were included in this systematic review. In all studies, the definitive diagnosis of diverticular bleeding was always made by urgent colonoscopy. The colonic diverticular bleeding stopped spontaneously in over 80% of the patients, but a re-bleeding was not rare. Recently, interventional endoscopy and angiography became the first-line approach, thus relegating emergency colectomy to patients presenting with hemodynamic instability or as a second-line treatment after failure or complications of hemostasis with less invasive treatments.Colonoscopy is effective to diagnose diverticular bleeding. Nowadays, interventional endoscopy and angiographic treatment have gained a leading role and colectomy should only be entertained in case of failure of the former. PMID- 26554769 TI - Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety. AB - A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P < 0.001) for MMRV versus MMR and 1.62 (95% CI 1.51, 1.70; P < 0.001) for MMRV versus MMR + V. Meanwhile, immune response to rubella component in MMRV group was slightly reduced, GMT ratios were 0.81 (95% CI 0.78, 0.85; P < 0.001) and 0.79 (95% CI 0.76, 0.83; P < 0.001), respectively. Well tolerated safety profiles were demonstrated except higher incidence of fever (relative risks 1.12-1.60) and measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence. PMID- 26554770 TI - The Incidence of Deep Vein Thrombosis in Asian Patients With Chronic Obstructive Pulmonary Disease. AB - Most studies have focused on the prevalence of deep vein thrombosis (DVT) and pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation in Caucasian populations. DVT is supposedly less likely to occur among Asians than Caucasians, and the primary purpose of this study was to determine the actual incidence of DVT in patients with COPD in Asian populations.We enrolled patients over the age of 40 with a diagnosis of COPD (International Classification of Diseases, Ninth Revision [ICD-9]: 490-492, 496; A-code: A323 and A325) between 1998 and 2008. The index date was the date of first-time COPD diagnosis. We excluded the patients who had been diagnosed with COPD and DVT (The International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 453.8) before index date. The control group was frequency-matched according to age (3-year stratum), sex, and the year of admission, at a 2:1 ratio. Patients were followed from index date to when either a diagnosis of DVT was made, death occurred, December 31, 2009 was reached, or when the patients withdrew from the National Health Insurance program.The overall incidence rate of DVT was 18.78 per 10,000 person-years in patients with COPD, and the adjusted hazard ration of DVT in patients with COPD was 1.38 (95% confidence interval 1.06-1.80), which was greater than patients without COPD after adjusting for age, sex, atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accident, congestive heart failure, lower leg fracture or surgery, and cancer.Asian patients with COPD had a higher incidence of DVT than non-COPD patients. PMID- 26554771 TI - Correlation of GLUT9 Polymorphisms With Gout Risk. AB - Single nucleotide polymorphisms (SNPs) at the glucose transporter 9 (GLUT9) locus are clearly related to uric acid concentrations previously identified as a major cause of gout. Due to the important function of various SNPs, we hypothesized that the common GLUT9 polymorphisms (rs16890979, rs6855911, and rs7442295) are associated with gout risk. The purpose of this investigation was to test the hypothesis.Gout risk was estimated by calculating odds ratios and 95% confidence intervals (ORs and 95% CIs). Either the fixed- or the random-effect model was used for OR calculations. Subgroup analyses were carried out by ethnicity for rs16890979 and by gender for all SNPs.We analyzed a total of 8 studies involving 2525 subjects for rs16890979, 2654 for rs6855911, and 2637 for rs7442295. A significantly declined risk was suggested in the meta-analyses of rs16890979 under dominant model (OR = 0.44, 95% CI = 0.34-0.58) and heterozygote model (OR = 0.44, 95% CI = 0.33-0.59). The OR was 0.41 under allele frequency model (OR = 0.41, 95% CI = 0.33-0.53). Significantly declined risk in relation to rs16890979 was also found among Asians. Similarly decreased risk was revealed for rs7442295, both in total samples and in males. However, the meta-analysis of rs6855911 revealed no significant associations.These data seem to support the hypothesis that the risk of gout may be associated with GLUT9 rs16890979 and rs7442295. PMID- 26554772 TI - Differing Clinical Courses and Prognoses in Patients With Gastric Neuroendocrine Tumors Based on the 2010-WHO Classification Scheme. AB - The aim of this study is to test the prognostic accuracy of the 2010-WHO classification for postsurgery survival in nonmetastatic gastric neuroendocrine tumor (NET) cases. Whether the 2010-WHO classification of NETs can predict relapse after surgical resection has not yet been established.We selected 175 nonmetastatic gastric NET patients at Asan Medical Center, Seoul, Korea between 1996 and 2013. All tumors were classified using the WHO-2010 scheme.Among 175 patients with gastric NETs, we diagnosed 39 cases as WHO grade 1, 13 cases as grade 2, 66 cases as grade 3 (neuroendocrine carcinomas; NECs), and 57 cases as mixed with adenocarcinoma. Patients with grade 3 had a lower relapse-free survival (RFS) and overall survival (OS) than those with WHO grade 1/2 and had a lower OS than patients with mixed type tumors. Patients with grade 1/2 had a better OS than patients with mixed type. There was no significant difference in RFS and OS between small and large cell type lesions. Among WHO grade 1/2 patients with <=1 cm sized lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion, and we detected no lymph node metastases or recurrences.Our findings strongly suggest that WHO grade 3 behaves more aggressively than adenocarcinoma. Additionally, the survival of cases with large and small cell NEC was similar. Among WHO grade 1/2 patients who had <=1 cm lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion and all could be treated by endoscopic resection or minimally invasive surgery without node dissection. PMID- 26554773 TI - Children With Intracranial Arachnoid Cysts: Classification and Treatment. AB - We performed a dynamic study of arachnoid cysts (ACs) using magnetic resonance cisternography (MRC) and proposed a classification of ACs.Twenty-three suitable patients in our hospital entered into this study according to our inclusion criteria. MRC images were collected in all the subjects at 1 and 24 hours after the administration of intrathecal gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA). We allocate the enrolled patients into 2 groups, MRC group and surgery group. The MRC results were considered before treatment in 1 group (MRC group, 13 patients), whereas another group was surgically treated without considering the MRC results (surgery group, 10 patients). We calculated the enhanced area of cyst using modified MacDonald Criteria from the images and measured the surrounding subarachnoid area as the reference.We found that it was practically useful to quantify 3 types of ACs, complete communicating, incomplete communicating, and noncommunicating, according to MRC results in this study. All the subjects in both groups are closely observed before the treatment and the follow-up using the MRI examination. In the surgery group, 5 patients were found that the area of cysts shrank in the follow-up stage. However, there was no significant difference in the percentage shrinkage area between the 2 groups.We concluded that MRC with Gd-DTPA as a contrast agent is of significant clinical value for the diagnosis and treatment of children with intracranial ACs. This classification based on dynamic MRC is useful for making surgical recommendations. PMID- 26554774 TI - Early Enteral Feeding After Living Donor Liver Transplantation Prevents Infectious Complications: A Prospective Pilot Study. AB - Infectious complications, including bacteria, virus, and fungus, often occur after liver transplantation and are the most frequent causes of in-hospital mortality. The current study prospectively analyze the effect of early enteral feeding in patients after living donor liver transplantation (LDLT)Between January 2013 and August 2013, 36 patients underwent LDLT. These patients were randomly assigned to receive enteral formula via nasointestinal feeding tubes [enteral feeding (EN) group, n = 17] or maintenance on intravenous fluid until oral diets were initiated (control group, n = 19). All patients completed the study.The pretransplant and perioperative characteristics of patients did not differ between the 2 groups. The incidence of bacterial infection was significantly lower in the EN group (29.4%) than in the control group (63.2%) (P = 0.043). In addition, the incidence of bile duct complications in the EN group was lower than in the control group (5.9% versus 31.6%, P = 0.041). Multivariate analysis showed that early enteral feeding was closely associated with bacterial infections (odds ratio, 0.178; P = 0.041). There was no statistically significant difference in nutritional status between the 2 groups. There were no cases of in hospital mortality.Early enteral feeding after LDLT prevents posttransplant bacterial infection, suggesting the possibility of a reduction of in-hospital mortality as a result of decreased infectious complications. PMID- 26554775 TI - Diagnostic Accuracy of Procalcitonin for Predicting Blood Culture Results in Patients With Suspected Bloodstream Infection: An Observational Study of 35,343 Consecutive Patients (A STROBE-Compliant Article). AB - Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study. Depending on blood culture results, patients were classified into 1 of the 5 following groups: negative blood culture, Gram-positive bacteremia, Gram-negative bacteremia, fungi, and potential contaminants found in blood cultures (PCBCs). The highest procalcitonin concentration was observed in patients with blood cultures growing Gram-negative bacteria (median 2.2 ng/mL [IQR 0.6-12.2]), and the lowest procalcitonin concentration was observed in patients with negative blood cultures (median 0.3 ng/mL [IQR 0.1-1.1]). With optimal thresholds ranging from <=0.4 to <=0.75 ng/mL, procalcitonin had a high diagnostic accuracy for excluding all pathogen categories with the following negative predictive values: Gram-negative bacteria (98.9%) (including enterobacteria [99.2%], nonfermenting Gram-negative bacilli [99.7%], and anaerobic bacteria [99.9%]), Gram-positive bacteria (98.4%), and fungi (99.6%). A procalcitonin concentration >=10 ng/mL was associated with a high risk of Gram-negative (odds ratio 5.98; 95% CI, 5.20-6.88) or Gram-positive (odds ratio 3.64; 95% CI, 3.11-4.26) bacteremia but dramatically reduced the risk of PCBCs or fungemia. In this large real-life setting experience with more than 35,000 patients, procalcitonin was highly effective at excluding bloodstream infections regardless of pathogen categories. The results from our study are limited by its cross-sectional design and deserve to be validated in prospective longitudinal studies. PMID- 26554776 TI - Paternal Hemizygosity in 11p15 in Mole-like Conceptuses: Two Case Reports. AB - Hydatidiform mole is an abnormal human pregnancy characterized by the fetus being absent or nonviable, and the chorionic villi being vesicular and with trophoblastic hyperplasia. Most often, the mole phenotype is seen in conceptuses with an excess of paternally inherited genome set(s) relative to maternally inherited genome set(s), suggesting that the phenotype is caused by an excess of genome with a paternal imprinting pattern. However, it is unknown if correct parental origin of every imprinted gene is crucial for normal early differentiation or if abnormal parental imprinting of only one, or some, gene(s) can cause the mole phenotype.Two conceptuses included in the Danish Mole Project stood out since they presented with vesicular chorionic villi and without signs of fetal differentiation, and had apparently biparental diploid genomes, and no mutations in NLRP7 or KHDC3L were detected in the mothers. These conceptuses were subjected to a centralized histopathological revision and their genetic complements were scrutinized using fluorescence in situ hybridization, and DNA marker and array comparative genomic hybridization analyses. Both conceptuses showed dysmorphic chorionic villi with some similarities to hydatidiform moles; however, no definite florid trophoblast hyperplasia was observed. Both conceptuses showed paternal hemizygosity of 11pter-11p15.4, most likely in nonmosaic state.Our findings suggest that the product of one (or a few) maternally expressed gene(s) on the tip of chromosome 11 is necessary for normal early embryonic differentiation. However, since the present two cases did not exhibit all features of hydatidiform moles, it is likely that abnormal parental imprinting of genes in other regions contribute to the phenotype of a hydatidiform mole. PMID- 26554777 TI - Relationship Between Urinary Cross-Linked N-Telopeptide of Type-I Collagen and Heel Stiffness Index Measured by Quantitative Ultrasound in Middle-Aged and Elderly Men. AB - The aim of the present study was to investigate the age-related patterns and the relationship between levels of urinary cross-linked N-telopeptide of type-I collagen (NTx) and heel stiffness index measured by quantitative ultrasound (QUS) in men with a special reference to age groups of aged 40 to 59 years and >=60 years.A total of 379 men participated in this study. Heel stiffness index (bone mass) was measured by QUS. Spot urine samples were collected, and urinary NTx was measured. The values were corrected for creatinine (Cre) concentration.Stiffness index was significantly lower in men aged >=60 years compared with men aged 40 to 59 years (P < 0.0001). There was no significant difference of Log (NTx/Cre) by 10 year age groups. Multiple regression analysis showed that higher level of urinary NTx/Cre was significantly correlated with lower stiffness index after adjusting for age and body mass index in men aged >=60 years, but not in men aged 40 to 59 years.Higher rates of bone resorption were associated with lower stiffness index only in elderly men. Our results may indicate a different mechanism of low bone mass among different age groups. PMID- 26554778 TI - Pulmonary Hypertension Complicating Fibrosing Mediastinitis. AB - Fibrosing mediastinitis is caused by a proliferation of fibrous tissue in the mediastinum with encasement of mediastinal viscera and compression of mediastinal bronchovascular structures. Pulmonary hypertension (PH) is a severe complication of fibrosing mediastinitis caused by extrinsic compression of the pulmonary arteries and/or veins.We have conducted a retrospective observational study reviewing clinical, functional, hemodynamic, radiological characteristics, and outcome of 27 consecutive cases of PH associated with fibrosing mediastinitis diagnosed between 2003 and 2014 at the French Referral Centre for PH.Fourteen men and 13 women with a median age of 60 years (range 18-84) had PH confirmed on right heart catheterization. The causes of fibrosing mediastinitis were sarcoidosis (n = 13), tuberculosis-infection confirmed or suspected (n = 9), mediastinal irradiation (n = 2), and idiopathic (n = 3). Sixteen patients (59%) were in NYHA functional class III and IV. Right heart catheterization confirmed moderate to severe PH with a median mean pulmonary artery pressure of 42 mm Hg (range 27-90) and a median cardiac index of 2.8 L/min/m (range 1.6-4.3). Precapillary PH was found in 22 patients, postcapillary PH in 2, and combined postcapillary and precapillary PH in 3. Severe extrinsic compression of pulmonary arteries (>60% reduction in diameter) was evidenced in 2, 8, and 12 patients at the main, lobar, or segmental levels, respectively. Fourteen patients had at least one severe pulmonary venous compression with associated pleural effusion in 6 of them. PAH therapy was initiated in 7 patients and corticosteroid therapy (0.5-1 mg/kg/day) was initiated in 3 patients with sarcoidosis, with 9 other being already on low-dose corticosteroids. At 1-year follow-up, 3 patients had died and among the 21 patients evaluated, 3 deteriorated, 14 were stable, and only 4 patients with sarcoidosis improved (4 receiving corticosteroids and 1 receiving corticosteroids and PAH therapy). Survival was 88%, 73%, and 56% at 1, 3, and 5 years, respectively.We found no clear clinical improvement with the use of specific PAH therapy. Corticosteroid therapy may be associated with clinical improvement, in some patients with fibrosing mediastinitis due to sarcoidosis. Although never performed for this indication, lung transplantation may be proposed in eligible patients with severe PH and fibrosing mediastinitis. PMID- 26554779 TI - Visit-to-Visit Glucose Variability Predicts the Development of End-Stage Renal Disease in Type 2 Diabetes: 10-Year Follow-Up of Taiwan Diabetes Study. AB - The purpose of this study was to examine the association of glucose variability using coefficient of variation of fasting plasma glucose (FPG-CV) and coefficient of variation of glycated hemoglobin (HbA1c-CV) to end-stage renal disease (ESRD) in 31,841 Chinese patients with type 2 diabetes.Patients with type 2 diabetes enrolled in National Diabetes Care Management Program, aged ?30 years, and free of ESRD (n = 31,841) in January 1, 2002 to December 31, 2004 were included. Extended Cox proportional hazards regression models with competing risk of all cause mortality were used to evaluate risk factors on ESRD incidence. Patients were followed till 2012.After a median follow-up period of 8.23 years, 1642 patients developed ESRD, giving a crude incidence rate of 6.27/1000 person-years (6.36 for men, 6.19 for women). After the multivariate adjustment, both FPG-CV and HbA1c-CV were independent predictors of ESRD with corresponding hazard ratios of 1.20 (95% confidence interval [CI] 1.01, 1.41), 1.24 (95% CI 1.05, 1.46) in HbA1c-CV from fourth to fifth quintile and 1.23 (95% CI 1.03, 1.47) in FPG-CV from fifth quintile.One-year visit-to-visit glucose variability expressed by FPG CV and HbA1c-CV predicted development of ESRD in patients with type 2 diabetes, suggesting therapeutic strategies toward a goal to minimize glucose fluctuation. PMID- 26554780 TI - COX-2 Promotes Migration and Invasion by the Side Population of Cancer Stem Cell Like Hepatocellular Carcinoma Cells. AB - Cancer stem cells (CSCs) are thought to be responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise to new tumors. Cyclooxygenase-2 (COX-2) is highly expressed in several kinds of CSCs, and it helps promote stem cell renewal, proliferation, and radioresistance. Whether and how COX-2 contributes to CSC migration and invasion is unclear. In this study, COX-2 was overexpressed in the CSC-like side population (SP) of the human hepatocellular carcinoma (HCC) cell line HCCLM3. COX-2 overexpression significantly enhanced migration and invasion of SP cells, while reducing expression of metastasis-related proteins PDCD4 and PTEN. Treating SP cells with the selective COX-2 inhibitor celecoxib down-regulated COX-2 and caused a dose dependent reduction in cell migration and invasion, which was associated with up regulation of PDCD4 and PTEN. These results suggest that COX-2 exerts pro metastatic effects on SP cells, and that these effects are mediated at least partly through regulation of PDCD4 and PTEN expression. These results further suggest that celecoxib may be a promising anti-metastatic agent to reduce migration and invasion by hepatic CSCs. PMID- 26554781 TI - Does Bowel Preparation for Colonoscopy Affect Cognitive Function? AB - Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and 40.0 (P = 0.59) at test 2, 38.6 and 40.8 (P = 0.76) at test 3.This study did not find evidence of cognitive impairment resulting from administration of bowel preparation before colonoscopy. PMID- 26554782 TI - The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma: A Large Case-control Study. AB - This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients.We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection.Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 +/- 0.6 vs 1.3 +/- 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 +/- 0.9 vs 1.0 +/- 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT.Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients. PMID- 26554783 TI - Air Pollution and the Risk of Cardiac Defects: A Population-Based Case-Control Study. AB - Previous epidemiologic studies have assessed the role of the exposure to ambient air pollution in the development of cardiac birth defects, but they have provided somewhat inconsistent results. To assess the associations between exposure to ambient air pollutants and the risk of cardiac defects, a population-based case control study was conducted using 1087 cases of cardiac defects and a random sample of 10,870 controls from 1,533,748 Taiwanese newborns in 2001 to 2007.Logistic regression was performed to calculate odds ratios for 10 ppb increases in O3 and 10 MUg/m increases in PM10. In addition, we compared the risk of cardiac defects in 4 categories-high exposure (>75th percentile); medium exposure (75th to 50th percentile); low exposure (<50th-25th percentile); reference (<25th percentile) based on the distribution of each pollutant. The risks of ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) were associated with 10 ppb increases in O3 exposure during the first 3 gestational months among term and preterm babies. In comparison between high PM10 exposure and reference category, there were statistically significant elevations in the effect estimates of ASD for all and terms births. In addition, there was a negative or weak association between SO2, NO2, CO, and cardiac defects.The study proved that exposure to outdoor air O3 and PM10 during the first trimester of gestation may increase the risk of VSD, ASD, and PDA. PMID- 26554784 TI - The Distribution and the Fibrotic Role of Elevated Inflammatory Th17 Cells in Patients With Primary Biliary Cirrhosis. AB - T helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease.We compared the circulating Th17 and hepatic interleukin (IL)-17 positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4CD161 populations were sorted and cultured with IL-23 and IL-1beta to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1beta were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of alpha-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17.Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4CD161 cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4CD161 cell. After stimulation with IL-23 and IL-1beta which were improved in PBC patients, CD4CD161 cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions.CD4CD161 cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater accumulation in the liver, which is regulated by CCL20 in advanced patients. IL-17 may be involved in the process of PBC fibrosis. PMID- 26554785 TI - A Case Report: The Diagnosis and Therapeutic Evaluation for a Rare Disease of Langerhans Cell Histiocytosis Involving Thyroid. AB - Langerhans cell histiocytosis (LCH) involving the thyroid gland is extremely rare. Currently, the diagnosis and therapeutic evaluation for LCH involving thyroid is a challenge.We reported a rare case of LCH involving thyroid, presenting as painless thyroid goiters, and successfully performed positron emission tomography/computed tomography (PET/CT) to make an accurate diagnosis and therapeutic evaluation for LCH.Although the histology or cytology is the golden standard for the diagnosis of LCH involving thyroid, the PET/CT should be keep in mind when LCH involving thyroid with inconclusive cytologic results. During the treatment of LCH, PET/CT can be performed to assess the therapeutic effect and select the most effective and reliable treatment for LCH. PMID- 26554786 TI - False-positive Uptake on Positron Emission Tomography/Computed Tomography Immediately After Lung Biopsy: A Case Report. AB - 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is an evolving tool in the field of oncology. 18F-fluorodeoxyglucose, however, is not a specific tool for malignant tumor that it may also accumulate in benign processes. To avoid false-positive interpretation of 18F-FDG-PET/computed tomography (CT), having knowledge of the potential pitfalls is important.The authors present a case of a patient with a lung mass who underwent fluoroscopy-guided transthoracic lung biopsy followed by 18F-FDG-PET/CT scan with a 4-hour interval between biopsy and scanning. Abnormally increased FDG uptake in the mass and pleural effusion was detected. Pathologic examination of the specimen, however, revealed only fibrous tissues with chronic inflammatory cells. On performing CT imaging, 1 month later, the mass and effusion had spontaneously resolved without treatment.Our findings suggest that PET/CT performed immediately following invasive procedures can result in false-positive results and thus mislead diagnosis. Therefore, the interval and order, in which PET/CT and invasive procedures are performed, should be carefully considered in oncologic work-up. PMID- 26554787 TI - Clinical and Ultrasonographic Evaluation of Lower-extremity Vein Thrombosis in Behcet Syndrome: An Observational Study. AB - Vascular involvement can be seen in up to 40% of patients with Behcet syndrome (BS), the lower-extremity vein thrombosis (LEVT) being the most common type. The aim of the current study was to compare venous Doppler findings and clinical features between BS patients with LEVT and control patients diagnosed as having LEVT due to other causes.All consecutive 78 patients (71 men, 7 women; mean age 38.6 +/- 10.3 years) with LEVT due to BS and 50 control patients (29 men, 21 women; mean age 42.0 +/- 12.5 years) who had LEVT due to other causes, or idiopathic, were studied with the help of a Doppler ultrasonography after a detailed clinical examination. Patterns of venous disease were identified by cluster analyses. Clinical features of chronic venous disease were assessed using 2 classification systems. Venous claudication was also assessed.Patients with BS were more likely to be men, had significantly earlier age of onset of thrombosis, and were treated mainly with immunosuppressives and less frequently with anticoagulants. Furthermore, they had significantly more bilateral involvement, less complete recanalization, and more frequent collateral formation. While control patients had a disorganized pattern of venous involvement, BS patients had a contiguous and symmetric pattern, involving all deep and superficial veins of the lower extremities, with less affinity for crural veins. Clinical assessment, as measured by the 2 classification systems, also indicated a more severe disease among the BS patients. In line, 51% of the BS patients suffered from severe post-thrombotic syndrome (PTS) and 32% from venous claudication, whereas these were present in 8% and 12%, respectively, among the controls. Among BS patients, a longer duration of thrombosis, bilateral femoral vein involvement, and using no anticoagulation along with immunosuppressive treatment when first diagnosed were found to be associated independently with severe PTS.Lower extremity vein thrombosis associated with BS, when compared to LEVT due to other causes, had distinctive demographic and ultrasonographic characteristics, and had clinically a more severe disease course. PMID- 26554788 TI - Immunologic Monitoring of T-Lymphocyte Subsets and Hla-Dr-Positive Monocytes in Kidney Transplant Recipients: A Prospective, Observational Cohort Study. AB - The clinical significance of circulating T-lymphocyte subsets and human leukocyte antigen (HLA)-DR-positive monocytes in the peripheral blood of kidney transplant recipients (KTRs) remains unclear. We examined the efficacy of enumerating these cells for the immunologic monitoring of KTRs.Blood samples were obtained before transplantation, 2 weeks after transplantation and at diagnosis, and 2 weeks after treating biopsy-proven acute cellular rejection and cytomegalovirus (CMV) infection. Serial flow cytometric analysis was performed using peripheral blood obtained from 123 patients to identify the frequencies of HLA-DR, CD3, CD4, CD8, and CD25 T-lymphocytes and HLA-DR-positive monocytes.Frequencies of CD4CD25/CD4 T cells, CD8CD25/CD8 T cells, and HLA-DR-positive monocytes were significantly lower at 2 weeks after transplantation than before transplantation (all P < 0.001). This decrease was not correlated with clinical parameters. The frequency of CD4CD25/CD4 T cells was significantly higher in KTRs with acute rejection than in KTRs at 2 weeks after transplantation (9.10% [range 4.30-25.6%] vs 5.10% [range 0.10-33.3%]; P = 0.024). However, no significant differences were observed between stable KTRs and KTRs with CMV infection. Analysis of the receiver operating characteristic curve adjusted by covariates showed that acute rejection could be predicted with 75.0% sensitivity and 68.4% specificity by setting the cutoff value of CD4CD25/CD4 T cell frequency as 5.8%.Circulating T-lymphocyte and monocyte subsets showed significant and consistent changes in their frequencies after immunosuppression. Of the various immune cells examined, circulating levels of CD4CD25 T cells might be a useful noninvasive immunologic indicator for detecting acute rejection. PMID- 26554789 TI - Treatment Outcomes From a Specialist Model for Treating Tobacco Use Disorder in a Medical Center. AB - Cigarette smoking causes premature mortality and multiple morbidity; stop smoking improves health. Higher rates of smoking cessation can be achieved through more intensive treatment, consisting of medication and extended counseling of patients, but there are challenges to integrating these interventions into healthcare delivery systems. A care model using a master-level counselor trained as a tobacco treatment specialist (TTS) to deliver behavioral intervention, teamed with a supervising physician/prescriber, affords an opportunity to integrate more intensive tobacco dependence treatment into hospitals, clinics, and other medical systems. This article analyzes treatment outcomes and predictors of abstinence for cigarette smokers being treated using the TTS physician team in a large outpatient clinic over a 7-year period.This is an observational study of a large cohort of cigarette smokers treated for tobacco dependence at a medical center. Patients referred by the primary healthcare team for a TTS consult received a standard assessment and personalized treatment planning guided by a workbook. Medication and behavioral plans were developed collaboratively with each patient. Six months after the initial assessment, a telephone call was made to ascertain a 7-day period of self-reported abstinence. The univariate association of each baseline patient characteristic with self reported tobacco abstinence at 6 months was evaluated using the chi-squared test. In addition, a multiple logistic regression analysis was performed with self reported tobacco abstinence as the dependent variable and all baseline characteristics included as explanatory variables.Over a period of 7 years (2005 2011), 6824 cigarette smokers who provided general research authorization were seen for treatment. The 6-month self-reported abstinence rate was 28.1% (95% confidence interval: 27.7-30.1). The patients most likely to report abstinence were less dependent, more motivated to quit, and did not have a past year diagnosis of depression or alcoholism.Predictable patient characteristics such as level of dependence did predict abstinence, but all patient groups achieved comparable abstinence outcomes. While this study has limitations inherent in a single-center retrospective cohort study, it does suggest that the TTS model is an effective way to integrate more intensive tobacco dependence treatment into outpatient settings. PMID- 26554790 TI - Serum Phosphorylated Neurofilament-Heavy Chain, a Potential Biomarker, is Associated With Peripheral Neuropathy in Patients With Type 2 Diabetes. AB - Neurofilament (NF), one of the major axonal cytoskeletal proteins, plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study is to explore the relationship between serum phosphorylated neurofilament-heavy chain (pNF-H) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.Serum pNF-H concentrations were measured by ELISA in hospitalized patients with and without DPN (n = 118). DPN was assessed by clinical symptoms, signs, and electromyography.Compared with the non-DPN group (311.98 [189.59-634.12] pg/mL), the confirmed group (605.99 [281.17 1332.78] pg/mL) patients had the higher serum pNF-H levels (P = 0.007). DPN was significantly correlated with C-peptide (r = -0.269), total cholesterol (TC) (r = 0.185), and pNF-H (r = 0.258). Serum pNF-H levels were independently associated with DPN (P = 0.004), even after adjusting for age, sex, duration of diabetes, fasting plasma glucose, glycosylated hemoglobin A1c, TC, C-peptide, urinary albuminto/creatinine ratio, and estimated glomerular filtration rate. Compared with pNF-H quartile 1 (referent), patients in quartile 3 (odds ratio [OR], 3.977; 95% confidence interval [CI], 1.243-12.728; P = 0.021) and quartile 4 (OR, 10.488; 95% CI, 3.020-34.429; P = 0.000) had the higher risk of DPN after adjusting for the confounders.Serum pNF-H levels might be associated with the DPN, and the correlationship between serum pNF-H and DPN should be further studied. PMID- 26554791 TI - Does an Obesity Paradox Really Exist After Cardiovascular Intervention?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies. AB - Several studies have shown the existence of an obesity paradox after Percutaneous Coronary Intervention (PCI). However, other studies have shown its absence. This study sought to perform a systematic review and meta-analysis of studies comparing the mortality risk between high body mass index patients and normal weight patients after PCI.We have searched PubMed, Embase, and Chinese medical journal for randomized controlled trials (RCTs) and observational studies published between the year 2000 and 2015 by typing the keywords "percutaneous coronary intervention" and "obesity paradox." The main outcome was "all-cause mortality". RevMan 5.3 software was used to calculate the risk ratio (RR) with 95% confidence interval (CI) to express the pooled effect on discontinuous variables.Twenty-two studies have been included in this meta-analysis consisting of a total of 242,377 patients with 73,143 normal weight patients, 103,608 overweight, and 65,626 obese patients. Younger age, higher cardiovascular risk factors and the intensive use of medications have mainly been observed among obese patients followed by overweight and normal weight patients respectively. In hospital, 12 months and >= 1 year (long-term) mortality risks were significantly lower in the overweight and obese groups with (RR: 0.67; 95% CI: 0.63-0.72, P < 0.00001) and (RR: 0.60; 95% CI: 0.56-0.65, P < 0.00001) respectively in the in hospital follow-up (RR: 0.62; 95% CI: 0.55-0.71 and 0.57; 95% CI: 0.52-0.63, P < 0.00001) at 12 months, and (RR: 0.70; 95% CI: 0.64-0.76; P < 0.00001) and (RR: 0.80; 95% CI: 0.71-0.91, P = 0.0006) respectively for the long-term follow-up after PCI.This "obesity paradox" does exist after PCI. The mortality in overweight and obese patients is really significantly lower compared to the normal weight patients. However, the exact reasons for this phenomenon need further exploration and research in the future. PMID- 26554792 TI - Impaired Aerobic Endurance and Muscular Strength in Substance Use Disorder Patients: Implications for Health and Premature Death. AB - Although substance use disorder (SUD) patients are documented to have an inactive lifestyle, which is associated with cardiovascular disease, other lifestyle related diseases and premature death, evidence regarding their aerobic endurance and muscular strength is limited. Therefore, the authors aimed to evaluate directly assessed maximal oxygen consumption, walking efficiency, as well as maximal strength in a group of SUD patients.A total of 44 SUD patients in residential treatment, 31 men (31 +/- 8 years) and 13 women (34 +/- 10 years), were included and completed the physical testing. The patients were compared with an age- and sex-matched reference group.Male and female SUD patients exhibited a maximal oxygen consumption of 44.6 +/- 6.2 and 33.8 +/- 6.6 mL. min kg, respectively. This was significantly lower than the reference group, 15% (P = 0.03) for men and 25% (P = 0.001) for women. In addition, the SUD patients had a 13% significantly reduced walking efficiency (P = 0.02), compared with healthy controls. The impairments in aerobic endurance were accompanied by significant reductions in maximal strength of 30% (P = 0.001) and 33% (P = 0.01) for men and women, respectively. In combination, these results imply that SUD patients have impaired endurance and muscular strength compared with what is typically observed in the population, and consequently suffer a higher risk of developing cardiovascular and other lifestyle-related diseases and early death. Effective physical exercise should be advocated as an essential part of the clinical practice of SUD treatment to improve the patient's health and consequently reduce the costs because of the high use of emergency departments, hospital, and medical care. PMID- 26554793 TI - Atorvastatin Treatment for Carotid Intima-Media Thickness in Chinese Patients With Type 2 Diabetes: A Meta-Analysis. AB - Impact of atorvastatin on carotid intima-media thickness (CIMT) in patients with type 2 diabetes is still debating.The aim of our study is to investigate atorvastatin as adjuvant treatment on CIMT in Chinese patients with type 2 diabetes by conducting a meta-analysis based on the randomized controlled trials (RCTs).A systematic search of electronic database of the Pubmed, EMBASE, Cochrane Library, VIP database, China National Knowledge Infrastructure, and Wangfang up to January 2015 was conducted. Randomized controlled trials (RCTs) comparing atorvastatin adjuvant treatment to the hypoglycemic therapies or high-dose atorvastatin versus low-dose atorvastatin therapies for patients with type 2 diabetes were selected.A total of 14 RCTs involving 1345 patients were included. Adjuvant treatment with atorvastatin was associated with a significant reduction in CIMT (weighted mean difference [WMD] = -0.17 mm; 95% confidence interval [CI] 0.22 to -0.12). Compared with the low-dose atorvastatin, high-dose atorvastatin treatment was associated with a significant reduction in CIMT (WMD = -0.17 mm; 95% CI: -0.32 to -0.02). Adjuvant treatment with atorvastatin reduced serum total cholesterol, triglyceride, low-density lipoproteins, and high sensitivity C reactive protein levels. However, atorvastatin had no significant impact on blood glucose levels.This meta-analysis demonstrated that treatment with atorvastatin significantly reduced CIMT in Chinese patients with type 2 diabetes. Moreover, high-dose atorvastatin appeared to have additional benefits in reducing CIMT than the low-dose atorvastatin. PMID- 26554794 TI - Validation Study of the Spanish Version of the Disability Assessment for Dementia Scale. AB - The aim of this study was to determine reliability and validity of the Spanish version of the Disability Assessment for Dementia Scale (DAD-E) in the following areas: content, response process, internal structure, and relation to other constructs.We designed a cross-sectional observational study. The DAD-E was administered to 132 participants diagnosed with mild cognitive decline, prodromal Alzheimer disease, Alzheimer disease, or no cognitive decline. For the reliability study, we performed analyses of internal consistency, test-retest, and equivalent measures. To study validity, we performed item analysis, principal components analysis, and correlations with other measures.The sample was composed of 37 healthy participants (28%) and 95 patients (72%). In the total scale, Cronbach alpha was 0.963, intraclass correlation coefficient in the test-retest analysis was 0.983 (95% CI [95% confidence interval] = 0.969-0.991), and the analysis for equivalent measures was 0.949 (95% CI = 0.897-0.975). Out of the 40 items, we found that 37 presented a correlation index with the total score above 0.40. The principal components analysis suggests that 61.7% of the variance is explained by a single component that groups all scores on Activities of Daily Living. The DAD total score presents correlations with Barthel's Index of 0.882 (P = 0.000) and with Lawton and Brodie's Index of 0.877 (P = 0.000) and with the Mini Mental State Examination of 0.679 (P = 0.000).The DAD-E is a reliable and valid instrument to assess functional disability in people with cognitive decline in Spanish population. PMID- 26554795 TI - Alteration of Heart Rate Variability in People With Bowel Preparation Before Colonoscopy. AB - In current health examination setting, people frequently undergo heart rate variability (HRV) analysis and colonoscopy on the same day. However, it remains unclear whether the bowel preparation before colonoscopy affects HRV. This study aimed to evaluate the association between HRV and bowel preparation.We conducted a cross-sectional observational study of 1755 people from January 2012 to December 2013 in Taipei, Taiwan. The participants, aged 45 to 65 years, received health examinations that included a physical examination, blood tests, and an HRV analysis. Among these people, 1099 additionally received a colonoscopy on the same day and underwent bowel preparation 1 day before the colonoscopy. The association between HRV and bowel preparation was derived by a multivariable linear regression with adjusted confounding factors.Bowel preparation was associated with a lower standard deviation of the normal-to-normal intervals (SDNN), the root mean square of the successive differences (RMSSD), low-frequency power (LF), and high-frequency power (HF) (all P < 0.0001). After adjusting confounding factors, bowel preparation remained correlated with lower SDNN, RMSSD, LF, and HF (all P < 0.0001). Higher serum phosphorus and lower serum potassium levels were noted in the bowel preparation group (P < 0.0001), and an association between lower HRV and higher serum phosphorus and lower serum potassium levels was only noted in the bowel preparation group.Bowel preparation was significantly associated with lower HRV. The underlying mechanism may be related to an electrolyte imbalance. Cautions may be needed when interpreting HRV reports for people receiving bowel preparations before colonoscopy. PMID- 26554796 TI - Bilateral Shoulder Dysfunction Related to the Lung Resection Area After Thoracotomy. AB - This study aimed to investigate the mobility, pain, and disability of the shoulders after different pulmonary surgical procedures.It is a cross-sectional prospective study. A total of 38 patients who underwent lung surgery via thoracotomy (mean age = 57 +/- 10 years) were evaluated in the preoperative period, and first and second postoperative days were assessed for range of motion of shoulder; pain intensity; and application of the Shoulder Pain and Disability Index questionnaire. This study compared the 3 days of evaluation, and the subgroups according to the resection area (biopsy/nodulectomy, lung segmentectomy and lobectomy).There was a decrease of flexion (153 degrees +/- 16 degrees -98 degrees +/- 23 degrees ), abduction (151 degrees +/- 20 degrees -126 degrees +/- 38 degrees ), and increased Shoulder Pain and Disability Index (2.4-44.3) in the shoulder ipsilateral to surgery from the preoperative to the first postoperative day (P < 0.05). There was a greater loss of ipsilateral flexion and abduction in the lobectomy subgroup (P < 0.05), and decreased abduction of the contralateral shoulder in the lung segmentectomy and lobectomy subgroups (P < 0.05).After pulmonary surgery, there is bilateral impairment in shoulder range of motion, with greater limitation on ipsilateral shoulder, and larger resections. PMID- 26554797 TI - Value of Magnifying Endoscopy With Narrow-Band Imaging and Confocal Laser Endomicroscopy in Detecting Gastric Cancerous Lesions. AB - Although the respective potentials of magnifying endoscopy with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE) in predicting gastric cancer has been well documented, there is a lack of studies in comparing the value and diagnostic strategy of these 2 modalities. Our primary aim is to investigate whether CLE is superior to ME-NBI for differentiation between gastric cancerous and noncancerous lesions. A secondary aim is to propose an applicable clinical strategy.We conducted a diagnostic accuracy study involving patients with suspected gastric superficial cancerous lesions. White light endoscopy, ME NBI, and CLE were performed diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value between ME-NBI and CLE were assessed, as well as agreements between ME-NBI/CLE and histopathology.This study involved 86 gastric lesions in 82 consecutive patients who underwent white light endoscopy, ME-NBI, and CLE before biopsy. The accuracy, sensitivity, and specificity for ME-NBI were 93.75%, 91.67%, and 95.45%, compared with 91.86%, 90%, and 93.48%, respectively, for CLE, for discrimination cancerous/noncancerous lesion (all P > 0.05). For undifferentiated/differentiated adenocarcinoma, CLE had a numerically but not statistically significantly higher accuracy than ME-NBI (81.25% vs 73.33%, P = 0.46). Agreements between ME-NBI/CLE and histopathology were near perfect (ME-NBI, kappa = 0.87; CLE, kappa = 0.84).CLE is not superior to ME-NBI for discriminating gastric cancerous from noncancerous lesions. Endoscopist could make an optimal choice according to the specific indication and advantages of ME-NBI and CLE in daily practices. PMID- 26554798 TI - Renal Denervation: A Potential Novel Treatment for Type 2 Diabetes Mellitus? AB - Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM.In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism.We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015.Studies were included if a statistical relationship was investigated between RDN and T2DM.The quality of each included study was assessed by Newcastle-Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles.In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity.Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded.If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies, RDN may emerge as a novel therapeutic option for patients with T2DM. PMID- 26554800 TI - Comparison Between Posterior Short-segment Instrumentation Combined With Lateral approach Interbody Fusion and Traditional Wide-open Anterior-Posterior Surgery for the Treatment of Thoracolumbar Fractures. AB - The aim of the study was to compare the radiographic and clinical outcomes between posterior short-segment pedicle instrumentation combined with lateral approach interbody fusion and traditional anterior-posterior (AP) surgery for the treatment of thoracolumbar fractures.Lateral-approach interbody fusion has achieved satisfactory results for thoracic and lumbar degenerative disease. However, few studies have focused on the use of this technique for the treatment of thoracolumbar fractures.Inclusion and exclusion criteria were established. All patients who meet the above criteria were prospectively treated by posterior short-segment instrumentation and secondary-staged minimally invasive lateral approach interbody fusion, and classified as group A. A historical group of patients who were treated by traditional wide-open AP approach was used as a control group and classified as group B. The radiological and clinical outcomes were compared between the 2 groups.There were 12 patients in group A and 18 patients in group B. The mean operative time and intraoperative blood loss of anterior reconstruction were significantly higher in group B than those in group A (127.1 +/- 21.7 vs 197.5 +/- 47.7 min, P < 0.01; 185.8 +/- 62.3 vs 495 +/- 347.4 mL, P < 0.01). Two of the 12 (16.7%) patients in group A experienced 2 surgical complications: 1 (8.3%) major and 1 (8.3%) minor. Six of the 18 (33%) patients in group B experienced 9 surgical complications: 3 (16.7%) major and 6 (33.3%) minor. There was no significant difference between the 2 groups regarding loss of correction (4.3 +/- 2.1 vs 4.2 +/- 2.4, P = 0.89) and neurological function at final follow-up (P = 0.77). In both groups, no case of instrumentation failure, pseudarthrosis, or nonunion was noted.Compared with the wide-open AP surgery, posterior short-segment pedicle instrumentation, combined with minimally invasive lateral-approach interbody fusion, can achieve similar clinical results with significant less operative time, blood loss, and surgical complication. This procedure seems to be a reasonable treatment option for selective patients with thoracolumbar fractures. PMID- 26554801 TI - The Difference of Clinical Characteristics Between Patients With Exon 19 Deletion and Those With L858R Mutation in Nonsmall Cell Lung Cancer. AB - Recent studies have demonstrated that exon 19 deletion (19 Del) and exon 21 L858R mutation (L858R) are 2 different types of sensitive epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). However, whether there are some differences between those 2 groups in baseline clinical characteristics is still unclear.We enrolled consecutive 1271 NSCLC patients detected with either 19 Del or L858R and collected their baseline clinical characteristics including age, sex, comorbidity, smoking and drinking status, body mass index (BMI), TNM stage, histologic type, differentiation, tumor maximum diameter (TMD), and CEA level. chi test and multivariate logistic regression analysis were used to compare the difference.We found a higher percentage of 19 Del in younger patients group (< = 50 yr) than L858R (P < 0.001) through chi test. Besides, patients with 19 Del have higher risk of lymph node metastasis (P < 0.001). However, there were no significant differences in other items of clinical characteristics between 19 Del and L858R. Multivariate analysis showed similar significant results. Subgroup analysis in different age groups (10 yr as an interval) and N stages (stratified by N0, N1, N2, and N3) also indicated above mentioned trends.NSCLC patients with 19 Del are more likely to be young and have lymphatic metastasis than those with L858R. Age and N stage might be considered in predicting EGFR mutation type in NSCLC. PMID- 26554799 TI - Cardiometabolic Risk Profiles in Patients With Impaired Fasting Glucose and/or Hemoglobin A1c 5.7% to 6.4%: Evidence for a Gradient According to Diagnostic Criteria: The PREDAPS Study. AB - It has been suggested that the early detection of individuals with prediabetes can help prevent cardiovascular diseases. The purpose of the current study was to examine the cardiometabolic risk profile in patients with prediabetes according to fasting plasma glucose (FPG) and/or hemoglobin A1c (HbA1c) criteria.Cross sectional analysis from the 2022 patients in the Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS Study) was developed. Four glycemic status groups were defined based on American Diabetes Association criteria. Information about cardiovascular risk factors-body mass index, waist circumference, blood pressure, cholesterol, triglycerides, uric acid, gamma glutamyltransferase, glomerular filtration-and metabolic syndrome components were analyzed. Mean values of clinical and biochemical characteristics and frequencies of metabolic syndrome were estimated adjusting by age, sex, educational level, and family history of diabetes.A linear trend (P < 0.001) was observed in most of the cardiovascular risk factors and in all components of metabolic syndrome. Normoglycemic individuals had the best values, individuals with both criteria of prediabetes had the worst, and individuals with only one-HbA1c or FPG-criterion had an intermediate position. Metabolic syndrome was present in 15.0% (95% confidence interval: 12.6-17.4), 59.5% (54.0-64.9), 62.0% (56.0-68.0), and 76.2% (72.8-79.6) of individuals classified in normoglycemia, isolated HbA1c, isolated FPG, and both criteria groups, respectively.In conclusion, individuals with prediabetes, especially those with both criteria, have worse cardiometabolic risk profile than normoglycemic individuals. These results suggest the need to use both criteria in the clinical practice to identify those individuals with the highest cardiovascular risk, in order to offer them special attention with intensive lifestyle intervention programs. PMID- 26554802 TI - Predictive Symptoms and Signs of Laboratory-confirmed Influenza: A Prospective Surveillance Study of Two Metropolitan Areas in Taiwan. AB - Influenza infection poses annual threats and leads to significant morbidity and mortality. Early diagnosis is the key to successful treatment. Laboratory-based diagnosis has various limitations. Diagnosis based on symptoms or signs is still indispensable in clinical practice. We investigated the symptoms or signs associated with laboratory-confirmed influenza.A prospective study across 2 influenza seasons was performed from June 2010 to June 2012 at 2 branches (Taipei and Lin-Kou) of Chang Gung Memorial Hospital. Patients who visited outpatient clinics with suspected acute respiratory tract infection were sampled by throat swab or nasopharyngeal swab. RT-PCR and/or virus culture were used as a reference standard. We used logistic regression to identify the symptoms or signs associated with laboratory-confirmed influenza infection. We also evaluated the performance metrics of different influenza-like illness used in Taiwan, the USA, and WHO.A total of 158 patients were included in the study. The prevalence of influenza infection was 45% (71/158). Fever, cough, rhinorrhea, sneezing, and nasal congestion were significant predictors for influenza infection. Whereas fever + cough had a best sensitivity (86%; confidence interval [CI] 76%-93%), fever + cough and sneezing had a best specificity (77%; CI 62%-88%). Different case definitions of influenza-like illness had comparable accuracy in sensitivity and specificity.Clinical diagnosis based on symptoms and signs is useful for allocating resources, identifying those who may benefit from early antiviral therapy and providing valuable information for surveillance purpose. PMID- 26554803 TI - Wider Perioperative Glycemic Fluctuations Increase Risk of Postoperative Acute Kidney Injury: A Prospective Cohort Study. AB - Acute kidney injury (AKI) is a common complication after cardiac surgery. Recent studies have revealed emerging associations between the magnitude of acute glycemic fluctuations and intensive care unit (ICU) mortality rates. However, the effect of acute glycemic fluctuations on the development of postoperative AKI remains unclear. Thus, we aim to investigate the effect of the magnitude of acute perioperative glycemic fluctuations on the incidence of postoperative AKI.We conducted a prospective cohort study by prospectively obtaining data from all patients who underwent elective coronary artery bypass grafting in a tertiary heart institution from 2009 to 2011. The magnitude of the difference between the highest and lowest perioperative glucose levels within 48 hr was calculated as a measure of perioperative glycemic fluctuation. Patients were divided into 4 groups for analysis based on the magnitude of perioperative glycemic fluctuation A: 0 to 2 mmol/L; B: >2 to 4 mmol/L; C: >4 to 6 mmol/L; and D: >6 mmol/L. We analyzed the incidence of postoperative AKI, ICU mortality and ICU length of stay as primary and secondary outcomes, respectively. Both univariate and multivariate analyses were used.We analyzed data from 1386 patients. The overall incidence of AKI was 29.9% and increased with wider glycemic fluctuation. The incidence of AKI was statistically highest in Group D (38.3%), followed by Groups C (28.6%), B (21.7%), and A (17.4%), respectively (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.001). A similar trend was observed among both diabetics and nondiabetics (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.001 and P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.002, respectively). Multivariate logistic regression showed the magnitude of perioperative glycemic fluctuations to be an independent risk factor in the development of AKI (P < 0.001, odds ratio 1.180, 95% confidence interval 1.116-1.247). ICU length of stay was statistically highest in Group D (58.3[REPLACEMENT CHARACTER]hr) compared with Groups C (44.5[REPLACEMENT CHARACTER]hr), B (37.3[REPLACEMENT CHARACTER]hr), and A (32.8[REPLACEMENT CHARACTER]hr, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.003). ICU mortality rate was comparable among all 4 groups (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.172).Wide acute perioperative glycemic fluctuations should be avoided as they are associated with a significantly increased risk of AKI and ICU length of stay in both the diabetics and the nondiabetics. PMID- 26554804 TI - Clinical Characteristics and Risk Factor Analysis for Lower-Extremity Amputations in Diabetic Patients With Foot Ulcer Complicated by Necrotizing Fasciitis. AB - Patients with diabetes are at a higher risk of having diabetic foot ulcers (DFUs) or necrotizing fasciitis (NF). The present study aims to examine the clinical characteristics and associated risk factors for lower-extremity amputation (LEA) in patients with DFU complicated by NF.We retrospectively reviewed patients treated at a major diabetic foot center in Taiwan between 2009 and 2014. Of the 2265 cases 110 had lower-extremity NF. Limb preservation outcomes were classified as major LEA, minor LEA, or limb-preserved. Clinical characteristics, laboratory data, and bacterial culture results were collected for analysis.Of the 110 patients with NF, 100 had concomitant DFUs (NF with DFU) and the remaining 10 had no DFU (NF without DFU). None of the NF patients without DFU died nor had their leg amputated. Two NF patients with DFU died of complications. The amputation rate in the surviving 98 NF patients with DFU was 72.4% (46.9% minor LEA and 25.5% major LEA). Seventy percent of the NF patients without DFU had monomicrobial infections (60% with Streptococcus species), and 81.4% NF patients with DFU had polymicrobial infections. Anaerobic organisms were identified in 66% of the NF patients with DFU. Multinomial logistic regression analysis revealed an association between high-grade Wagner wound classification (Wagner 4 and Wagner 5) and LEA (adjusted odds ratio [aOR] = 21.856, 95% confidence interval [95% CI] = 1.625-203.947, P = 0.02 and aOR = 20.094, 95% CI = 1.968-205.216, P = 0.01 for major and minor LEA, respectively) for NF patients with DFU. In addition, a lower serum albumin level was associated with major LEA (OR = 0.066, P = 0.002).In summary, once DFUs were complicated by NF, the risk of amputation increased. Empirical treatment for NF patients with DFU should cover polymicrobial infections, including anaerobic organisms. The high-grade wound classification and low serum albumin level were associated with LEA. PMID- 26554805 TI - Demonstrating a Conceptual Framework to Provide Efficient Wound Management Service for a Wound Care Center in a Tertiary Hospital. AB - Although the benefits of wound care services and multidisciplinary team care have been well elaborated on in the literature, there is a gap in the actual practice of wound care and the establishment of an efficient referral system. The conceptual framework for establishing efficient wound management services requires elucidation.A wound care center was established in a tertiary hospital in 2010, staffed by an integrated multidisciplinary team including plastic surgeons, a full-time coordinator, a physical therapist, occupational therapists, and other physician specialists. Referral patients were efficiently managed following a conceptual framework for wound care. This efficient wound management service consists of 3 steps: patient entry and onsite immediate wound debridement, wound re-evaluation, and individual wound bed preparation plan. Wound conditions were documented annually over 4 consecutive years.From January 2011 to December 2014, 1103 patients were recruited from outpatient clinics or inpatient consultations for the 3-step wound management service. Of these, 62% of patients achieved healing or improvement in wounds, 13% of patients experienced no change, and 25% of patients failed to follow-up. The outcome of wound treatment varied by wound type. Sixty-nine percent of diabetic foot ulcer patients were significantly healed or improved. In contrast, pressure ulcers were the most poorly healed wound type, with only 55% of patients achieving significantly healed or improved wounds.The 3-step wound management service in the wound care center efficiently provided onsite screening, timely debridement, and multidisciplinary team care. Patients could schedule appointments instead of waiting indefinitely for care. Further wound condition follow-up, education, and prevention were also continually provided. PMID- 26554806 TI - Clinical Outcomes and Complications of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasms in the Elderly. AB - The number of elderly people with superficial gastric neoplasms is increasing, but the clinical outcome of endoscopic submucosal dissection (ESD) for treating elderly people with superficial gastric neoplasms remains unclear. We aimed to compare the efficacy and safety of ESD for patients with early gastric cancer (EGC) and precancerous lesions in elderly (>=75 years of age) and nonelderly (<75 years of age) patients.From October 2005 to December 2014, 83 consecutive patients with EGC and precancerous lesions (86 lesions) who were treated using ESD in our hospital were retrospectively reviewed. There were 44 lesions in 42 elderly patients who were at least 75-years old. The following parameters were compared between the 2 groups: preexisting comorbidities, performance status (PS), lesion inclusion criteria, lesion characteristics, treatment outcomes, surgery time, duration of hospitalization, complications, and intraoperative hemodynamic changes.Elderly patients had significantly higher preexisting comorbidity rates (90.9% vs 59.5%, P = 0.001), expanded lesion criteria rates (43.2% vs 19.0%, P = 0.016), and lower best PS rates (38.6% vs 81.0%, P < 0.001) than nonelderly patients. Lesion characteristics were similar in the 2 groups. The elderly had higher intraoperative hypotension rates (47.7% vs 21.4%, P = 0.011) and oxygen desaturation rates (9.1% vs 0.0%, P = 0.045) than nonelderly patients. In addition, the elderly also had a longer surgery time (107.0 +/- 51.4 vs 91.5 +/- 66.2 minutes, P = 0.049) and duration of hospitalization (7.5 +/- 3.8 vs 5.9 +/- 2.0 days, P = 0.016) than nonelderly patients. There were no differences in the prevalence rates of en-bloc resection, complete resection, bleeding, perforation, pneumonia, or intraabdominal free air between the 2 groups.Although elderly patients who underwent ESD for superficial gastric neoplasms had an increasing risk of intraoperative hypotension and oxygen desaturation, all patients were treated appropriately without postoperative sequelae. ESD is a safe and feasible intervention for elderly patients who have more comorbidity, a worse PS and more expanded lesions. PMID- 26554807 TI - Physical Activity, Study Sitting Time, Leisure Sitting Time, and Sleep Time Are Differently Associated With Obesity in Korean Adolescents: A Population-Based Study. AB - Low physical activity, long leisure sitting time, and short sleep time are risk factors for obesity, but the association with study sitting time is unknown. The objective of this study was to evaluate the association between these factors and obesity.We analyzed the association between physical activity, study sitting time, leisure sitting time, and sleep time and subject weight (underweight, healthy weight, overweight, and obese), using data from a large population-based survey, the 2013 Korea Youth Risk Behavior Web-based Survey. Data from 53,769 participants were analyzed using multinomial logistic regression analyses with complex sampling. Age, sex, region of residence, economic level, smoking, stress level, physical activity, sitting time for study, sitting time for leisure, and sleep time were adjusted as the confounders.Low physical activity (adjusted odds ratios [AORs] = 1.03, 1.12) and long leisure sitting time (AORs = 1.15, 1.32) were positively associated with overweight and obese. Low physical activity (AOR = 1.33) and long leisure sitting time (AOR = 1.12) were also associated with underweight. Study sitting time was negatively associated with underweight (AOR = 0.86) but was unrelated to overweight (AOR = 0.97, 95% confidence interval [CI] = 0.91-1.03) and obese (AOR = 0.94, 95% CI = 0.84-1.04). Sleep time (<6 hours; >=6 hours, <7 hours; >=7 hours, <8 hours) was adversely associated with underweight (AORs = 0.67, 0.79, and 0.88) but positively associated with overweight (AORs = 1.19, 1.17, and 1.08) and obese (AORs = 1.33, 1.36, and 1.30) in a dose-response relationship.In adolescents, increasing physical activity, decreasing leisure sitting time, and obtaining sufficient sleep would be beneficial in maintaining a healthy weight. However, study sitting time was not associated with overweight or obese. PMID- 26554808 TI - Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography. AB - Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [F]2 Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (>=10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan-Meir survival analysis between high TLG50 (>2000) and low TLG50 (<=2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 +/- 134.3 days and 1968.6 +/- 18.3 days, respectively (P < 0.001).High TLG50 on [F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients. PMID- 26554809 TI - Traumatic Vertebral Fractures and Concomitant Fractures of the Rib in Southwest China, 2001 to 2010: An Observational Study. AB - To our knowledge, the clinical characteristics of traumatic vertebral fractures and concomitant fractures of the rib (TVF-RF) have not been described in previous studies.To investigate the clinical characteristics of patients managed for TVF RF. A retrospective study of 3142 patients who presented with traumatic vertebral fractures was performed. Two hundred twenty-six patients (7.2%) suffered from TVF RF.Incidence rate ratios were then calculated with respect to the level of injury to the spine, the ASIA classification of neurological deficits and age.There were 171 male (75.7%) and 55 female (24.3%) patients with a mean age of 43.8 years. The most common mechanisms were falls from high heights in 81 cases and road traffic crashes in 67 cases. Right-sided rib injury occurred in 106 cases, left sided injury occurred in 76 cases, and bilateral injury occurred in 44 cases. The most frequent location of the rib fractures was from the fourth rib to the ninth rib (70.3%, 510/725). Initial pulmonary complications (IPC) after trauma occurred in 116 cases (51.3%). The mortality rate for the entire group was 1.3% (3/226). The patients with thoracic vertebral fractures and neurological deficits had a higher frequency of multiple rib fractures and IPC than the other patients (P < 0.05). With the increased number of rib fractures, the frequency of IPC and mean intensive care unit (ICU) length of stay also increased.The rates of complications for patients with rib fractures were significantly different from those without rib fractures. We should pay much attention to the patients who presented with thoracic vertebral fractures and neurological deficits for minimizing further complications and mortality in such patients who had a higher frequency of multiple rib fractures and IPC than the other patients. PMID- 26554810 TI - Nurses' Own Recordkeeping: The Nursing Minimum Data Set Revisited. AB - There is no consistent, standardized, concise method for nurses to record information about their patients and clients that is conducive to store, retrieve, and use in patient and client care; to improve professional self development; and to use in collaboration with patients and clients, their families, other nurses, doctors, hospitals, and health systems. Nurses gauge the health status of their patients and clients every day and are now in a position both to record their impressions for their own use and to share them with colleagues who care for the same patients and clients. What is now needed is a way to record these clinical impressions within an authoritative format that is related to the depth and breadth of the clinical literature related to nursing and the needs of the patients and clients nurses serve. The International Council of Nurses' Nurse-Patient Summary is proposed here to fill the gulf between narrative nurses' notes, proprietary and widely varying electronic health record systems, and information from nurses about their patiens and clients human needs. The International Council of Nurses' Nurse-Patient Summary could replace nursing diagnosis items in the Nursing Minimum Data Set and serve as a substitute for the World Health Organization's International Classification of Function, Disability and Health, a seldom used instrument derived from the International Council of Nurses' Basic Principles of Nursing Care. PMID- 26554811 TI - Correction: Nitrogen-fluorine co-doped titania inverse opals for enhanced solar light driven photocatalysis. AB - Correction for 'Nitrogen-fluorine co-doped titania inverse opals for enhanced solar light driven photocatalysis' by T. K. Rahul et al., Nanoscale, 2015, 7, 18259-18270. PMID- 26554812 TI - Making SENSE--Sustained Effort Network for treatment of Status Epilepticus as a multicenter prospective registry. AB - BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725. PMID- 26554813 TI - What are the similarities and differences in structure and function among the three main models of community health centers in China: a systematic review. AB - BACKGROUND: There are three major models of primary care providers (Community Health Centers, CHCs) in China, i.e., government managed, hospital managed and privately owned CHCs. We performed a systematic review of structures and health care delivery patterns of the three models of CHCs. METHODS: Studies from relevant English and Chinese databases for the period of 1997-2011 were searched. Two independent researchers extracted data from the eligible studies using a standardized abstraction form. Methodological quality of included articles was assessed with the Mixed Methods Appraisal Tool (MMAT). RESULTS: A total of 13 studies was included in the final analysis. Compared with the other two models, private CHCs had a smaller health workforce and lower share of government funding in their total revenues. Private CHCs also had fewer training opportunities, were less recognized by health insurance schemes and tended to provide primary care services of poor quality. Hospital managed CHCs attracted patients through their higher quality of clinical care, while private CHCs attracted users through convenience and medical equipment. CONCLUSIONS: Our study suggested that government and hospital managed CHCs were more competent and provided better primary care than privately owned CHCs. Further studies are warranted to comprehensively compare performances among different models of CHCs. PMID- 26554814 TI - Quantifying Geometric Strain at the PbS QD-TiO2 Anode Interface and Its Effect on Electronic Structures. AB - Quantum dots (QDs) show promise as the absorber in nanostructured thin film solar cells, but achieving high device efficiencies requires surface treatments to minimize interfacial recombination. In this work, lead sulfide (PbS) QDs are grown on a mesoporous TiO2 film with a crystalline TiO2 surface, versus one coated with an amorphous TiO2 layer by atomic layer deposition (ALD). These mesoporous TiO2 films sensitized with PbS QDs are characterized by X-ray and electron diffraction, as well as X-ray absorption spectroscopy (XAS) in order to link XAS features with structural distortions in the PbS QDs. The XAS features are further analyzed with quantum simulations to probe the geometric and electronic structure of the PbS QD-TiO2 interface. We show that the anatase TiO2 surface structure induces PbS bond angle distortions, which increases the energy gap of the PbS QDs at the interface. PMID- 26554815 TI - New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions. AB - Amyloid aggregates display striking features of detergent stability and self seeding. Human serum albumin (HSA), a preferred drug-carrier molecule, can also aggregate in vitro. So far, key amyloid properties of stability against ionic detergents and self-seeding, are unclear for HSA aggregates. Precautions against amyloid contamination would be required if HSA aggregates were self-seeding. Here, we show that HSA aggregates display detergent sarkosyl stability and have self-seeding potential. HSA dimer is preferable for clinical applications due to its longer retention in circulation and lesser oedema owing to its larger molecular size. Here, HSA was homodimerized via free cysteine-34, without any potentially immunogenic cross-linkers that are usually pre-requisite for homodimerization. Alike the monomer, HSA dimers also aggregated as amyloid, necessitating precautions while using for therapeutics. PMID- 26554816 TI - Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration. AB - Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor (SRF) that promotes the expression of genes associated with cell proliferation, motility, adhesion, and differentiation-processes that also involve dynamic cytoskeletal changes in the cell. MKL1 is inactive when bound to monomeric globular actin (G-actin), but signals that activate the small guanosine triphosphatase RhoA cause actin polymerization and MKL1 dissociation from G actin. We found a new mechanism of MKL1 activation that is mediated through its binding to filamin A (FLNA), a protein that binds filamentous actin (F-actin). The interaction of FLNA and MKL1 was required for the expression of MKL1 target genes in primary fibroblasts, melanoma, mammary and hepatocellular carcinoma cells. We identified the regions of interaction between MKL1 and FLNA, and cells expressing an MKL1 mutant that was unable to bind FLNA exhibited impaired cell migration and reduced expression of MKL1-SRF target genes. Induction and repression of MKL1-SRF target genes correlated with increased or decreased MKL1 FLNA interaction, respectively. Lysophosphatidic acid-induced RhoA activation in primary human fibroblasts promoted the association of endogenous MKL1 with FLNA, whereas exposure to an actin polymerization inhibitor dissociated MKL1 from FLNA and decreased MKL1-SRF target gene expression in melanoma cells. Thus, FLNA functions as a positive cellular transducer linking actin polymerization to MKL1 SRF activity, counteracting the known repressive complex of MKL1 and monomeric G actin. PMID- 26554817 TI - Activation of mTORC1 in skeletal muscle regulates whole-body metabolism through FGF21. AB - Skeletal muscle is the largest organ, comprising 40% of the total body lean mass, and affects whole-body metabolism in multiple ways. We investigated the signaling pathways involved in this process using TSCmKO mice, which have a skeletal muscle specific depletion of TSC1 (tuberous sclerosis complex 1). This deficiency results in the constitutive activation of mammalian target of rapamycin complex 1 (mTORC1), which enhances cell growth by promoting protein synthesis. TSCmKO mice were lean, with increased insulin sensitivity, as well as changes in white and brown adipose tissue and liver indicative of increased fatty acid oxidation. These differences were due to increased plasma concentrations of fibroblast growth factor 21 (FGF21), a hormone that stimulates glucose uptake and fatty acid oxidation. The skeletal muscle of TSCmKO mice released FGF21 because of mTORC1 triggered endoplasmic reticulum (ER) stress and activation of a pathway involving PERK (protein kinase RNA-like ER kinase), eIF2alpha (eukaryotic translation initiation factor 2alpha), and ATF4 (activating transcription factor 4). Treatment of TSCmKO mice with a chemical chaperone that alleviates ER stress reduced FGF21 production in muscle and increased body weight. Moreover, injection of function-blocking antibodies directed against FGF21 largely normalized the metabolic phenotype of the mice. Thus, sustained activation of mTORC1 signaling in skeletal muscle regulated whole-body metabolism through the induction of FGF21, which, over the long term, caused severe lipodystrophy. PMID- 26554818 TI - Instructive roles for cytokine-receptor binding parameters in determining signaling and functional potency. AB - Cytokines dimerize cell surface receptors to activate signaling and regulate many facets of the immune response. Many cytokines have pleiotropic effects, inducing a spectrum of redundant and distinct effects on different cell types. This pleiotropy has hampered cytokine-based therapies, and the high doses required for treatment often lead to off-target effects, highlighting the need for a more detailed understanding of the parameters controlling cytokine-induced signaling and bioactivities. Using the prototypical cytokine interleukin-13 (IL-13), we explored the interrelationships between receptor binding and a wide range of downstream cellular responses. We applied structure-based engineering to generate IL-13 variants that covered a spectrum of binding strengths for the receptor subunit IL-13Ralpha1. Engineered IL-13 variants representing a broad range of affinities for the receptor exhibited similar potencies in stimulating the phosphorylation of STAT6 (signal transducer and activator of transcription 6). Delays in the phosphorylation and nuclear translocation of STAT6 were only apparent for those IL-13 variants with markedly reduced affinities for the receptor. From these data, we developed a mechanistic model that quantitatively reproduced the kinetics of STAT6 phosphorylation for the entire spectrum of binding affinities. Receptor endocytosis played a key role in modulating STAT6 activation, whereas the lifetime of receptor-ligand complexes at the plasma membrane determined the potency of the variant for inducing more distal responses. This complex interrelationship between extracellular ligand binding and receptor function provides the foundation for new mechanism-based strategies that determine the optimal cytokine dose to enhance therapeutic efficacy. PMID- 26554820 TI - Overcoming Film Quality Issues for Conjugated Polymers Doped with F4TCNQ by Solution Sequential Processing: Hall Effect, Structural, and Optical Measurements. AB - We demonstrate that solution-sequential processing (SqP) can yield heavily doped pristine-quality films when used to infiltrate the molecular dopant 2,3,5,6 tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) into pure poly(3 hexylthiophene) (P3HT) polymer layers. Profilometry measurements show that the SqP method produces doped films with essentially the same surface roughness as pristine films, and 2-D grazing-incidence wide-angle X-ray scattering (GIWAXS) confirms that SqP preserves both the size and orientation of the pristine polymer's crystallites. Unlike traditional blend-cast F4TCNQ/P3HT doped films, our sequentially processed layers have tunable and reproducible conductivities reaching as high as 5.5 S/cm even when measured over macroscopic (>1 cm) distances. The high conductivity and superb film quality allow for meaningful Hall effect measurements, which reveal p-type conduction and carrier concentrations tunable from 10(16) to 10(20) cm(-3) and hole mobilities ranging from ~0.003 to 0.02 cm(2) V(-1) s(-1) at room temperature over the doping levels examined. PMID- 26554821 TI - Autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease in a child. Case report and review of the literature. AB - BACKGROUND: Liver disease is rare in the course of mixed connective tissue disease. Most commonly liver steatosis or elevated liver function tests are reported and only a few cases of mixed connective tissue disease associated with autoimmune hepatitis were described. CASE PRESENTATION: We report a case of an 11 year old boy with hepatitis on admission to the hospital and symptoms and signs of mixed connective tissue disease. Autoimmune hepatitis has been confirmed by liver biopsy. CONCLUSION: To the best of our knowledge this is the youngest patient with autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease. PMID- 26554819 TI - The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling. AB - Protein arginine methylation regulates diverse functions of eukaryotic cells, including gene expression, the DNA damage response, and circadian rhythms. We showed that arginine residues within the third intracellular loop of the human D2 dopamine receptor, which are conserved in the DOP-3 receptor in the nematode Caenorhabditis elegans, were methylated by protein arginine methyltransferase 5 (PRMT5). By mutating these arginine residues, we further showed that their methylation enhanced the D2 receptor-mediated inhibition of cyclic adenosine monophosphate (cAMP) signaling in cultured human embryonic kidney (HEK) 293T cells. Analysis of prmt-5-deficient worms indicated that methylation promoted the dopamine-mediated modulation of chemosensory and locomotory behaviors in C. elegans through the DOP-3 receptor. In addition to delineating a previously uncharacterized means of regulating GPCR (heterotrimeric guanine nucleotide binding protein-coupled receptor) signaling, these findings may lead to the development of a new class of pharmacological therapies that modulate GPCR signaling by changing the methylation status of these key proteins. PMID- 26554823 TI - High-resolution Manometry Findings in Patients After Sclerotherapy for Esophageal Varices. AB - BACKGROUND/AIMS: Endoscopic therapy for esophageal varices may lead to esophageal dysmotility. High-resolution manometry is probably the more adequate tool to measure esophageal motility in these patients. This study aimed to evaluate esophageal motility using high resolution manometry following eradication of esophageal varices by endoscopic sclerotherapy. METHODS: We studied 21 patients (11 women, age 52 [45-59] years). All patients underwent eradication of esophageal varices with endoscopic sclerotherapy and subsequent high resolution manometry. RESULTS: A significant percentage of defective lower esophageal sphincter (basal pressure 14.3 [8.0-20.0] mmHg; 43% hypertonic) and hypocontractility (distal esophageal amplitude 50 [31-64] mmHg; proximal esophageal amplitude 40 [31-61] mmHg; distal contractile integral 617 [403-920] mmHg.sec.cm; 48% ineffective) was noticed. Lower sphincter basal pressure and esophageal amplitude correlated inversely with the number of sessions (P < 0.001). No manometric parameter correlated with symptoms or interval between last endoscopy and manometry. CONCLUSIONS: Esophageal motility after endoscopic sclerotherapy is characterized by: (1) defective lower sphincter and (2) defective and hypotensive peristalsis. Esophageal dysmotility is associated to an increased number of endoscopic sessions, but manometric parameters do not predict symptoms. PMID- 26554822 TI - All that is blood is not schistosomiasis: experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings. AB - BACKGROUND: Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected. METHODS: Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories. RESULTS: We found a "background" prevalence of microhaematuria (13 %, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection. CONCLUSIONS: Reagent strip testing for microhaematuria remains a good proxy for urogenital schistosomiasis, but implications of test results and scope of application differ depending on the setting in which reagent strips are employed. In very-low prevalence settings, microhaematuria is an unstable proxy for urogenital schistosomiasis and treatment decision should not be based on reagent strip test results alone. Our findings underscore the need for highly accurate diagnostic tools for settings targeted for elimination of urogenital schistosomiasis. PMID- 26554824 TI - Juvenile idiopathic arthritis and rheumatoid arthritis: bacterial diversity in temporomandibular joint synovial fluid in comparison with immunological and clinical findings. AB - Temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) occurs in up to 80% of affected children. The purpose of this study was to investigate the presence of bacterial DNA in synovial fluid, and to compare this with clinical and immunological findings in children with JIA, adults with persistent JIA, and adults with rheumatoid arthritis, in order to detect whether bacteria contribute to inflammation in TMJ arthritis. Synovial fluid and skin swab samples were collected from 30 patients (54 TMJs). Bacterial detection was performed using 16S rRNA pyrosequencing. Bacterial DNA was detected in 31 TMJs (57%) in 19 patients (63%). A positive statistically significant correlation was registered between bacterial DNA detected in TMJ synovial fluid and the following factors: total protein concentration in synovial fluid, interleukin 1beta, tumour necrosis factor alpha, adrenocorticotropic hormone, and adiponectin, as well as the duration of the general medical disease. Fourteen different bacterial species were detected in synovial fluid. Bacterial DNA in TMJ synovial fluid without contamination was detected in more than 50% of the patients. Studies are needed to evaluate the consequences of this bacterial DNA in synovial fluid with regard to TMJ arthritis. PMID- 26554825 TI - Characterisation of the Oxygenation Response to Inspired Oxygen Adjustments in Preterm Infants. AB - BACKGROUND: Oxygen saturation (SpO2) targeting in the preterm infant may be improved with a better understanding of the SpO2 responses to changes in inspired oxygen (FiO2). OBJECTIVE: We investigated the first-order FiO2-SpO2 relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. METHODS: In recordings of FiO2 and SpO2 from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO2 adjustments and mapped the subsequent SpO2 responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. RESULTS: In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO2 adjustments followed by a first-order SpO2 response. All response parameters differed between FiO2 increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p < 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO2 instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. CONCLUSIONS: First-order SpO2 responses show variable gain, influenced by the direction of FiO2 adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO2 for SpO2 targeting in preterm infants. PMID- 26554826 TI - Evaluation of procalcitonin postmortem levels in some models of death: An experimental study. AB - Post-mortem determination of biochemical parameters, especially for obscure cases, has been recognized useful in diagnosis of the underlying causes of death. Procalcitonin (PCT) is known to rise in a response to any proinflammatory stimulus. The present study aims to estimate postmortem PCT levels in serum and kidney, liver, brain; and whether it is similar in different causes of death models (trauma, drowning and freezing) models or not. The study was performed on 60 male rabbits. Rabbits were divided into four different death induced models (15 rabbit each): trauma, infection, drowning and freezing models. At the end of the study, all rabbits were sacrificed; blood samples, kidneys, livers and brains were collected. PCT was measured using ELISA assay. Results showed highly significant increase in PCT levels in all tested samples in different models of death. The infection induced model showed the highest levels in all tested samples compared to other groups mainly in liver; followed by trauma model and drowning model which were increased mainly in brain's samples. The least model which showed increased PCT levels was the freezing model mainly in liver samples. Post Hoc multiple comparisons test showed significant differences between groups in most of liver, brain and kidney samples, while PCT serum blood samples were significant only between trauma and infection groups. It was concluded that PCT can differentiate between sepsis and non-sepsis related deaths and that organs like liver, kidney and brain PCT levels could be an alternative to serum PCT for the diagnosis of postmortem sepsis. PMID- 26554827 TI - p73 and IGF1R Regulate Emergence of Aggressive Cancer Stem-like Features via miR 885-5p Control. AB - Cancer stem-like cells (CSC) have been proposed to promote cancer progression by initiating tumor growth at distant sites, suggesting that stem-like cell features can support metastatic efficiency. Here, we demonstrate that oncogenic DNp73, a dominant-negative variant of the tumor-suppressor p73, confers cancer cells with enhanced stem-like properties. DNp73 overexpression in noninvasive melanoma and lung cancer cells increased anchorage-independent growth and elevated the expression of the pluripotency factors CD133, Nanog, and Oct4. Conversely, DNp73 depletion in metastatic cells downregulated stemness genes, attenuated sphere formation and reduced the tumor-initiating capability of spheroids in tumor xenograft models. Mechanistic investigations indicated that DNp73 acted by attenuating expression of miR-885-5p, a direct regulator of the IGF1 receptor (IGF1R) responsible for stemness marker expression. Modulating this pathway was sufficient to enhance chemosensitivity, overcoming DNp73-mediated drug resistance. Clinically, we established a correlation between low p73 function and high IGF1R/CD133/Nanog/Oct4 levels in melanoma specimens that associated with reduced patient survival. Our work shows how DNp73 promotes cancer stem-like features and provides a mechanistic rationale to target the DNp73-IGF1R cascade as a therapeutic strategy to eradicate CSC. PMID- 26554828 TI - Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma. AB - Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. PMID- 26554829 TI - Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer. AB - The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radionuclide Indium-111 ((111)In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of (111)In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Coinjection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of (111)In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of (111)In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. PMID- 26554830 TI - Combined MYC Activation and Pten Loss Are Sufficient to Create Genomic Instability and Lethal Metastatic Prostate Cancer. AB - Genetic instability, a hallmark feature of human cancers including prostatic adenocarcinomas, is considered a driver of metastasis. Somatic copy number alterations (CNA) are found in most aggressive primary human prostate cancers, and the overall number of such changes is increased in metastases. Chromosome 10q23 deletions, encompassing PTEN, and amplification of 8q24, harboring MYC, are frequently observed, and the presence of both together portends a high risk of prostate cancer-specific mortality. In extant genetically engineered mouse prostate cancer models (GEMM), isolated MYC overexpression or targeted Pten loss can each produce early prostate adenocarcinomas, but are not sufficient to induce genetic instability or metastases with high penetrance. Although a previous study showed that combining Pten loss with focal MYC overexpression in a small fraction of prostatic epithelial cells exhibits cooperativity in GEMMs, additional targeted Tp53 disruption was required for formation of metastases. We hypothesized that driving combined MYC overexpression and Pten loss using recently characterized Hoxb13 transcriptional control elements that are active in prostate luminal epithelial cells would induce the development of genomic instability and aggressive disease with metastatic potential. Neoplastic lesions that developed with either MYC activation alone (Hoxb13-MYC) or Pten loss alone (Hoxb13-Cre?Pten(Fl/Fl)) failed to progress beyond prostatic intraepithelial neoplasia and did not harbor genomic CNAs. By contrast, mice with both alterations (Hoxb13-MYC?Hoxb13-Cre?Pten(Fl/Fl), hereafter, BMPC mice) developed lethal adenocarcinoma with distant metastases and widespread genome CNAs that were independent of forced disruption of Tp53 and telomere shortening. BMPC cancers lacked neuroendocrine or sarcomatoid differentiation, features uncommon in human disease but common in other models of prostate cancer that metastasize. These data show that combined MYC activation and Pten loss driven by the Hoxb13 regulatory locus synergize to induce genomic instability and aggressive prostate cancer that phenocopies the human disease at the histologic and genomic levels. PMID- 26554831 TI - Differential Regulation of 6- and 7-Transmembrane Helix Variants of MU-Opioid Receptor in Response to Morphine Stimulation. AB - The pharmacological effect of opioids originates, at the cellular level, by their interaction with the MU-opioid receptor (mOR) resulting in the regulation of voltage-gated Ca2+ channels and inwardly rectifying K+ channels that ultimately modulate the synaptic transmission. Recently, an alternative six trans-membrane helix isoform of mOR, (6TM-mOR) has been identified, but its function and signaling are still largely unknown. Here, we present the structural and functional mechanisms of 6TM-mOR signaling activity upon binding to morphine. Our data suggest that despite the similarity of binding modes of the alternative 6TM mOR and the dominant seven trans-membrane helix variant (7TM-mOR), the interaction with morphine generates different dynamic responses in the two receptors, thus, promoting the activation of different mOR-specific signaling pathways. We characterize a series of 6TM-mOR-specific cellular responses, and observed that they are significantly different from those for 7TM-mOR. Morphine stimulation of 6TM-mOR does not promote a cellular cAMP response, while it increases the intracellular Ca2+ concentration and reduces the cellular K+ conductance. Our findings indicate that 6TM-mOR has a unique contribution to the cellular opioid responses. Therefore, it should be considered as a relevant target for the development of novel pharmacological tools and medical protocols involving the use of opioids. PMID- 26554833 TI - Quantitative Pedagogy: A Digital Two Player Game to Examine Communicative Competence. AB - Inner concepts are much richer than the words that describe them. Our general objective is to inquire what are the best procedures to communicate conceptual knowledge. We construct a simplified and controlled setup emulating important variables of pedagogy amenable to quantitative analysis. To this aim, we designed a game inspired in Chinese Whispers, to investigate which attributes of a description affect its capacity to faithfully convey an image. This is a two player game: an emitter and a receiver. The emitter was shown a simple geometric figure and was asked to describe it in words. He was informed that this description would be passed to the receiver who had to replicate the drawing from this description. We capitalized on vast data obtained from an android app to quantify the effect of different aspects of a description on communication precision. We show that descriptions more effectively communicate an image when they are coherent and when they are procedural. Instead, the creativity, the use of metaphors and the use of mathematical concepts do not affect its fidelity. PMID- 26554832 TI - Venous Thrombosis Risk after Cast Immobilization of the Lower Extremity: Derivation and Validation of a Clinical Prediction Score, L-TRiP(cast), in Three Population-Based Case-Control Studies. AB - BACKGROUND: Guidelines and clinical practice vary considerably with respect to thrombosis prophylaxis during plaster cast immobilization of the lower extremity. Identifying patients at high risk for the development of venous thromboembolism (VTE) would provide a basis for considering individual thromboprophylaxis use and planning treatment studies. The aims of this study were (1) to investigate the predictive value of genetic and environmental risk factors, levels of coagulation factors, and other biomarkers for the occurrence of VTE after cast immobilization of the lower extremity and (2) to develop a clinical prediction tool for the prediction of VTE in plaster cast patients. METHODS AND FINDINGS: We used data from a large population-based case-control study (MEGA study, 4,446 cases with VTE, 6,118 controls without) designed to identify risk factors for a first VTE. Cases were recruited from six anticoagulation clinics in the Netherlands between 1999 and 2004; controls were their partners or individuals identified via random digit dialing. Identification of predictor variables to be included in the model was based on reported associations in the literature or on a relative risk (odds ratio) > 1.2 and p <= 0.25 in the univariate analysis of all participants. Using multivariate logistic regression, a full prediction model was created. In addition to the full model (all variables), a restricted model (minimum number of predictors with a maximum predictive value) and a clinical model (environmental risk factors only, no blood draw or assays required) were created. To determine the discriminatory power in patients with cast immobilization (n = 230), the area under the curve (AUC) was calculated by means of a receiver operating characteristic. Validation was performed in two other case-control studies of the etiology of VTE: (1) the THE-VTE study, a two-center, population-based case control study (conducted in Leiden, the Netherlands, and Cambridge, United Kingdom) with 784 cases and 523 controls included between March 2003 and December 2008 and (2) the Milan study, a population-based case-control study with 2,117 cases and 2,088 controls selected between December 1993 and December 2010 at the Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. The full model consisted of 32 predictors, including three genetic factors and six biomarkers. For this model, an AUC of 0.85 (95% CI 0.77-0.92) was found in individuals with plaster cast immobilization of the lower extremity. The AUC for the restricted model (containing 11 predictors, including two genetic factors and one biomarker) was 0.84 (95% CI 0.77-0.92). The clinical model (consisting of 14 environmental predictors) resulted in an AUC of 0.77 (95% CI 0.66-0.87). The clinical model was converted into a risk score, the L-TRiP(cast) score (Leiden-Thrombosis Risk Prediction for patients with cast immobilization score), which showed an AUC of 0.76 (95% CI 0.66-0.86). Validation in the THE-VTE study data resulted in an AUC of 0.77 (95% CI 0.58-0.96) for the L-TRiP(cast) score. Validation in the Milan study resulted in an AUC of 0.93 (95% CI 0.86 1.00) for the full model, an AUC of 0.92 (95% CI 0.76-0.87) for the restricted model, and an AUC of 0.96 (95% CI 0.92-0.99) for the clinical model. The L TRiP(cast) score resulted in an AUC of 0.95 (95% CI 0.91-0.99). Major limitations of this study were that information on thromboprophylaxis was not available for patients who had plaster cast immobilization of the lower extremity and that blood was drawn 3 mo after the thrombotic event. CONCLUSIONS: These results show that information on environmental risk factors, coagulation factors, and genetic determinants in patients with plaster casts leads to high accuracy in the prediction of VTE risk. In daily practice, the clinical model may be the preferred model as its factors are most easy to determine, while the model still has good predictive performance. These results may provide guidance for thromboprophylaxis and form the basis for a management study. PMID- 26554834 TI - Missense Mutations in LRP5 Associated with High Bone Mass Protect the Mouse Skeleton from Disuse- and Ovariectomy-Induced Osteopenia. AB - The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli. PMID- 26554835 TI - Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4 Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage. AB - Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4 nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities. PMID- 26554836 TI - Food Composition Database Format and Structure: A User Focused Approach. AB - This study aimed to investigate the needs of Australian food composition database user's regarding database format and relate this to the format of databases available globally. Three semi structured synchronous online focus groups (M = 3, F = 11) and n = 6 female key informant interviews were recorded. Beliefs surrounding the use, training, understanding, benefits and limitations of food composition data and databases were explored. Verbatim transcriptions underwent preliminary coding followed by thematic analysis with NVivo qualitative analysis software to extract the final themes. Schematic analysis was applied to the final themes related to database format. Desktop analysis also examined the format of six key globally available databases. 24 dominant themes were established, of which five related to format; database use, food classification, framework, accessibility and availability, and data derivation. Desktop analysis revealed that food classification systems varied considerably between databases. Microsoft Excel was a common file format used in all databases, and available software varied between countries. User's also recognised that food composition databases format should ideally be designed specifically for the intended use, have a user friendly food classification system, incorporate accurate data with clear explanation of data derivation and feature user input. However, such databases are limited by data availability and resources. Further exploration of data sharing options should be considered. Furthermore, user's understanding of food composition data and databases limitations is inherent to the correct application of non-specific databases. Therefore, further exploration of user FCDB training should also be considered. PMID- 26554838 TI - Particulate pollutant source evaluation using an inverse method under steady state conditions. AB - This article presents a method that enables the generation rate from one or /more particle sources to be estimated, using far-field concentration measurements. The method is made up of two distinct steps; a calibration phase, followed by an estimation phase. The calibration phase makes it possible to create a transfer relationship between a known source ("reference source") and the measurement of the far-field concentration. The second step consists of estimating unknown source generation rates by inverting the transfer relationship and using measurements of far-field concentrations resulting from these unknown sources. In addition, this article presents a technique to improve the positioning of the sensors in the room in which the sources are situated. A numerical study using computational fluid dynamics was first conducted to theoretically validate the estimation method and assist with choosing the sensor positions in the experimental rig. The study established that, with ideal sensors, the difference between the real and estimated generation rates can be accurate to within 0.1%. The method was then deployed on an experimental case. The results confirmed that it is possible to estimate an isolated source. However, the quality of the estimation deteriorated when the source to be estimated was significantly different from the reference source, from an aerodynamic perspective. PMID- 26554837 TI - Natural Guided Genome Engineering Reveals Transcriptional Regulators Controlling Quorum-Sensing Signal Degradation. AB - Quorum-quenching (QQ) are natural or engineered processes disrupting the quorum sensing (QS) signalling which controls virulence and persistence (e.g. biofilm) in numerous bacteria. QQ involves different enzymes including lactonases, amidases, oxidases and reductases which degrade the QS molecules such as N acylhomoserine lactones (NAHL). Rhodococcus erythropolis known to efficiently degrade NAHL is proposed as a biocontrol agent and a reservoir of QQ-enzymes for biotechnology. In R. erythropolis, regulation of QQ-enzymes remains unclear. In this work, we performed genome engineering on R. erythropolis, which is recalcitrant to reverse genetics, in order to investigate regulation of QQ enzymes at a molecular and structural level with the aim to improve the QQ activity. Deep-sequencing of the R. erythropolis enhanced variants allowed identification of a punctual mutation in a key-transcriptional factor QsdR (Quorum sensing degradation Regulation) which regulates the sole QQ-lactonase QsdA identified so far. Using biophysical and structural studies on QsdR, we demonstrate that QQ activity can be improved by modifying the regulation of QQ enzymes degrading QS signal. This modification requiring the change of only one amino-acid in a transcriptional factor leads to an enhanced R. erythropolis in which the QS-signal degradation pathway is strongly activated. PMID- 26554840 TI - Effects of nano-TiO2 on perfluorooctanesulfonate bioaccumulation in fishes living in different water layers: Implications for enhanced risk of perfluorooctanesulfonate. AB - Nano-titanium dioxide (nano-TiO2) is one of the most universal engineered nano materials while perfluorooctanesulfonate (PFOS) is a typical new persistent organic pollutant. They are widely used and present in aquatic environment. In this study, a novel semi-static multilayer microcosm was setup to investigate the impacts of nano-TiO2 on PFOS bioaccumulation in fish species [Danio rerio (D. rerio), Ctenopharyngodon idella (C. idella), Hypostomus plecostomus (H. plecostomus)] living in different vertical layers. As a result of aggregation and deposition, the concentration of TiO2 increased from upper to bottom layers in the water column. Concomitantly, due to adsorption of PFOS on the nano-TiO2 particles, PFOS also displayed an increasing trend from upper to bottom layer. Owing to ingestion of the TiO2-PFOS complexes, more PFOS was taken-up by fish. With the aid of intestinal fluid, PFOS was readily released from TiO2 particles and absorbed by fish. As a result, accumulation of PFOS in whole fish was facilitated and the bioaccumulation factors of PFOS in D. rerio, C. idella and H. plecostomus were 3.01, 2.42 and 1.11 times of that in the groups without TiO2. However, TiO2 aggregates were too large to penetrate biological membranes to participate body circulation, and no significant accumulation of TiO2 was observed in fish muscle. The results suggested that the ecological risk of PFOS could be enhanced due to the presence of nano-TiO2 in water. PMID- 26554839 TI - Predictors of Study Attrition in a Randomized Controlled Trial Evaluating a Perinatal Home-Visiting Program with Mothers with Psychosocial Vulnerabilities. AB - OBJECTIVE: Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France. MATERIALS AND METHODS: CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors. RESULTS: Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL 90) at 3 months postpartum were the only variables associated with later attrition. CONCLUSION: This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program. PMID- 26554841 TI - Proteome Differences in Placenta and Endometrium between Normal and Intrauterine Growth Restricted Pig Fetuses. AB - Uteroplacental tissue plays a key role in substance exchanges between maternal and fetal circulation, and, therefore, in the growth and development of fetuses. In this study, proteomics and western blotting were applied to investigate the changes of proteome in the placenta and endometrium of normal and intrauterine growth restriction (IUGR) porcine fetuses during mid to late pregnancy (D60, 90, and 110 of gestation). Our results showed that proteins participating in cell structure, energy metabolism, stress response, cell turnover, as well as transport and metabolism of nutrients were differentially expressed in placenta and endometrium between normal and IUGR fetuses. Analysis of functions of these proteins suggests reductions in ATP production and nutrients transport, increases in oxidative stress and apoptosis, and impairment of cell metabolism in IUGR fetuses. Collectively, our findings aid in understanding of the mechanisms responsible for uteroplacental dysfunction in IUGR fetus, and are expected to provide new strategies to reduce fetal growth restriction in pigs and other mammals. PMID- 26554842 TI - An In-Depth Examination of Perceptions of Physical Activity in Regularly Active and Insufficiently Active Older African American Women: A Participatory Approach. AB - Despite considerable research and programmatic efforts to alleviate racial/ethnic disparities in physical activity (PA), disparities in PA among older minorities and major racial ethnic groups persist. This study explored perceptions of PA among regularly active (RA) and insufficiently active (IA) older African American women (AAW) and the factors that influence (positively and negatively) their physical participation in their socio-cultural environment. A total of 20 AAW aged 60 to 80 years participated in a cross-sectional mixed-methods study (i.e., qualitative and quantitative) employing participatory research approaches (i.e., photoelicitation) along with an objective assessment of PA. Nine women were considered RA and 11 IA according to current PA recommendations. RA and IA women held two major beliefs about the nature of PA (i.e., PA as a broadly defined construct that goes beyond traditional exercise routines; and PA and exercise are synonymous and can be used interchangeably) and had a good understanding of its benefits. Participants in both groups did not know about the importance of PA intensity for health benefits. Barriers and facilitator of PA were found to be similar among RA and IA participants. Special attention should be paid to providing access to no or low cost opportunities for PA participation in safe environments. PMID- 26554844 TI - Deficiency of respiratory chain complex I in Hashimoto thyroiditis. AB - Oncocytic cells (OCs) are characterized by an accumulation of mitochondria and their occurrence in the thyroid gland of patients with Hashimoto thyroiditis (HT) is well known. However, their properties and functional relevance are poorly understood. We investigated OC lesions (n=212) in the thyroid of 12 HT patients. Loss of complex I protein was observed in oncocytic lesions of each of the patients. In addition to isolated complex I deficiency, 25% of oncocytic lesions showed combined deficiency of complex I and IV. Thus, we demonstrate for the first time a defect of respiratory chain complex I in OCs of HT patients. PMID- 26554843 TI - Easy to learn, hard to suppress: The impact of learned stimulus-outcome associations on subsequent action control. AB - The inhibition of impulsive response tendencies that conflict with goal-directed action is a key component of executive control. An emerging literature reveals that the proficiency of inhibitory control is modulated by expected or unexpected opportunities to earn reward or avoid punishment. However, less is known about how inhibitory control is impacted by the processing of task-irrelevant stimulus information that has been associated previously with particular outcomes (reward or punishment) or response tendencies (action or inaction). We hypothesized that stimulus features associated with particular action-valence tendencies, even though task irrelevant, would modulate inhibitory control processes. Participants first learned associations between stimulus features (color), actions, and outcomes using an action-valence learning task that orthogonalizes action (action, inaction) and valence (reward, punishment). Next, these stimulus features were embedded in a Simon task as a task-irrelevant stimulus attribute. We analyzed the effects of action-valence associations on the Simon task by means of distributional analysis to reveal the temporal dynamics. Learning patterns replicated previously reported biases; inherent, Pavlovian-like mappings (action reward, inaction-punishment avoidance) were easier to learn than mappings conflicting with these biases (action-punishment avoidance, inaction-reward). More importantly, results from two experiments demonstrated that the easier to learn, Pavlovian-like action-valence associations interfered with the proficiency of inhibiting impulsive actions in the Simon task. Processing conflicting associations led to more proficient inhibitory control of impulsive actions, similar to Simon trials without any association. Fast impulsive errors were reduced for trials associated with punishment in comparison to reward trials or trials without any valence association. These findings provide insight into the temporal dynamics of task irrelevant information associated with action and valence modulating cognitive control. We discuss putative mechanisms that might explain these interactions. PMID- 26554845 TI - Neural mechanisms of hypnosis and meditation. AB - Hypnosis has been an elusive concept for science for a long time. However, the explosive advances in neuroscience in the last few decades have provided a "bridge of understanding" between classical neurophysiological studies and psychophysiological studies. These studies have shed new light on the neural basis of the hypnotic experience. Furthermore, an ambitious new area of research is focusing on mapping the core processes of psychotherapy and the neurobiology/underlying them. Hypnosis research offers powerful techniques to isolate psychological processes in ways that allow their neural bases to be mapped. The Hypnotic Brain can serve as a way to tap neurocognitive questions and our cognitive assays can in turn shed new light on the neural bases of hypnosis. This cross-talk should enhance research and clinical applications. An increasing body of evidence provides insight in the neural mechanisms of the Meditative Brain. Discrete meditative styles are likely to target different neurodynamic patterns. Recent findings emphasize increased attentional resources activating the attentional and salience networks with coherent perception. Cognitive and emotional equanimity gives rise to an eudaimonic state, made of calm, resilience and stability, readiness to express compassion and empathy, a main goal of Buddhist practices. Structural changes in gray matter of key areas of the brain involved in learning processes suggest that these skills can be learned through practice. Hypnosis and Meditation represent two important, historical and influential landmarks of Western and Eastern civilization and culture respectively. Neuroscience has beginning to provide a better understanding of the mechanisms of both Hypnotic and Meditative Brain, outlining similarities but also differences between the two states and processes. It is important not to view either the Eastern or the Western system as superior to the other. Cross fertilization of the ancient Eastern meditation techniques presented with Western modern clinical hypnosis will hopefully result in each enriching the other. PMID- 26554847 TI - Diminution of miR-340-5p levels is responsible for increased expression of ABCB5 in melanoma cells under oxygen-deprived conditions. AB - Melanoma is usually highly refractory to chemotherapy. This resistance to treatment is mainly due to high heterogeneity and plasticity of melanoma cells strictly connected to changes in tumor microenvironment. Hypoxia can drastically alter cancer biology. Solid tumor cells under hypoxia gain stem-like features, they are more invasive and drug-resistant than their normoxic counterparts. These effects could be mediated by changes in miRNA expression under hypoxia. MiRNAs are small non-coding RNA molecules that can negatively control gene expression. In the present study using microarray technology we evaluated the expression of miRNAs in melanoma cells derived from nodular melanoma and grown under normoxic and hypoxic conditions. Using R environment for statistical analysis we found that 70 miRNAs were differentially-expressed, and 16 of them were significantly down-regulated in melanoma cells grown in hypoxic conditions compared to cells grown in normoxia. We intended to find transcripts whose expression is increased due to down-regulation of selected miRNAs. Bioinformatics analysis revealed that increased levels of HIF-2alpha, ABCB5, OCT4, SOX2 and ZEB1 in different melanoma populations under hypoxia could be a result of significant down-regulation of miR 340-5p. Inhibition of miR-340-5p confirmed that this miRNA negatively influences the expression of ABCB5. This is the first study showing the relationship between miR-340-5p and expression of ABCB5, a transmembrane transporter involved in drug resistance considered as a marker of melanoma stem-like cells. PMID- 26554846 TI - A census of alpha-helical membrane proteins in double-stranded DNA viruses infecting bacteria and archaea. AB - BACKGROUND: Viruses are the most abundant and genetically diverse biological entities on earth, yet the repertoire of viral proteins remains poorly explored. As the number of sequenced virus genomes grows into the thousands, and the number of viral proteins into the hundreds of thousands, we report a systematic computational analysis of the point of first-contact between viruses and their hosts, namely viral transmembrane (TM) proteins. RESULTS: The complement of alpha helical TM proteins in double-stranded DNA viruses infecting bacteria and archaea reveals large-scale trends that differ from those of their hosts. Viruses typically encode a substantially lower fraction of TM proteins than archaea or bacteria, with the notable exception of viruses with virions containing a lipid component such as a lipid envelope, internal lipid core, or inner membrane vesicle. Compared to bacteriophages, archaeal viruses are substantially enriched in membrane proteins. However, this feature is not always stable throughout the evolution of a viral lineage; for example, TM proteins are not part of the common heritage shared between Lipothrixviridae and Rudiviridae. In contrast to bacteria and archaea, viruses almost completely lack proteins with complicated membrane topologies composed of more than 4 TM segments, with the few detected exceptions being obvious cases of relatively recent horizontal transfer from the host. CONCLUSIONS: The dramatic differences between the membrane proteomes of cells and viruses stem from the fact that viruses do not depend on essential membranes for energy transformation, ion homeostasis, nutrient transport and signaling. PMID- 26554848 TI - Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction. AB - BACKGROUND: In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway. METHODS: Myocardial infarction (MI) was induced in twenty male Sprague Dawley rats. The rats were randomized into two groups and were then received the injection of 5 * 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI. Six weeks later, relevant signaling molecules involved were all examined. RESULTS: In the CSCs group, an increased expression of Cx43 could be observed in different zones of the left ventricle (P<0.01). There was a significant reduction of the angiotensin II (ANG II) level in plasma and different regions of the left ventricular cardiac tissues (P<0.05; P<0.01). The angiotensin II type I receptor (AT1R) was decreased accompanied with an enhanced expression of angiotensin II type II receptor (AT2R) (P<0.01). Transforming growth factor beta-1(TGF-beta1) was downregulated (P<0.01). The expression of mothers against decapentaplegic homolog (SMAD) proteins including SMAD2 and SMAD3 was attenuated whereas SMAD7 was elevated (P<0.01, P<0.01, P<0.05). In addition, the expression of mitogen-activated protein kinases (MAPKs) including extracellular kinases 1/2 (ERK1/2) and p38 was also found to be reduced (P<0.01). CONCLUSION: CSCs transplantation could enhance the level of Cx43 after MI. They might function through intervening the ANGII/AT1R/TGF-beta1 signaling pathway to regulate the expression of Cx43. PMID- 26554850 TI - Tumor microenvironment (TME)-driven immune suppression in B cell malignancy. AB - Immune checkpoint blockade antibodies and immunomodulatory drugs can unleash anti tumor T cell immunity and mediate durable cancer regressions. However, only a fraction of patients currently respond to immunotherapy. Lymphoid malignancies are known to have clinically exploitable immune sensitivity and their intrinsic lymphoid tumor-microenvironment (TME) should make them natural targets for immunotherapy. However, accumulating evidence is showing that malignant cells engage in novel associations/interdependencies with reprogrammed immune and stromal cells in the TME that provide crucial contributions to the licencing of tumour progression and immune evasion (suppression of antitumor immune responses). In this review, we outline TME-driven contributions to the licencing of immune evasion mechanisms including the expression and activity of the immune checkpoint network, focussing on two types of B cell malignancy: indolent chronic lymphocytic leukemia (CLL) and aggressive diffuse large B-cell lymphoma (DLBCL). We also highlight recent therapeutic strategies to re-educate the TME to have anti-tumorigenic effects. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. PMID- 26554849 TI - Sequence-function correlations and dynamics of ERG isoforms. ERG8 is the black sheep of the family. AB - The transcription factor ERG is known to have divergent roles. On one hand, it acts as differentiation factor of endothelial cells. On the other hand, it has pathological roles in various cancers. Genomic analyses of the ERG gene show that it gives rise to several isoforms. However, functional differences between these isoforms, representing potential reasons for distinct effects in diverse cell types have not been addressed in detail so far. We set out to investigate the major protein isoforms and found that ERG8 contains a unique C-terminus. This isoform, when expressed as GFP-fusion protein, localized mainly to the cytosol, whereas the other major isoforms (ERG1-4) were predominantly nuclear. Using site directed mutagenesis and laser scanning microscopy of live cells, we could identify nuclear localization (NLS) and nuclear export sequences (NES). These analyses indicated that ERG8 lacks a classical NLS and the DNA-binding domain, but holds an additional NES within its distinctive C-terminus. All the tested isoforms were shuttling between nucleus and cytosol and showed a high degree of mobility. ERG's 1 to 4 were transcriptionally active on ERG-promoter elements whereas ERG8 was inactive, which is in line with the absence of a DNA-binding domain. Fluorescence resonance energy transfer (FRET) microscopy revealed that ERG8 can bind to the transcriptionally active ERG's. Knockdown of ERG8 in endothelial cells resulted in upregulation of endogenous ERG-transcriptional activity implying ERG8 as an inhibitor of the active ERG isoforms. Quantitative PCR revealed a different ratio of active ERG's to ERG8 in cancer- versus non transformed cells. PMID- 26554853 TI - Supplemental Peri-Operative Oxygen and Incision Site Infection after Surgery for Perforated Peptic Ulcer: A Randomized, Double-Blind Monocentric Trial. AB - BACKGROUND: The clinical role of hyperoxia for preventing surgical site infection (SSI) remains uncertain because randomized controlled trials on this topic have reported disparate results. One of the principal reasons for this outcome may be that prior trials have entered heterogeneous populations of patients and a variety of procedures. The aim of our study was to assess the influence of hyperoxygenation on SSI using a homogeneous study population. METHODS: From January 2004 to April 2013, we studied, in a randomized trial, 239 patients, who underwent open surgery for perforated peptic ulcer (PPU). The surgical procedure was performed through an upper abdominal midline incision, and closure of PPU was achieved by suture alone or in combination with an omental patch. Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 120) or 80% (n = 119). Administration was commenced after induction of anesthesia and maintained for 6 hours after surgery. RESULTS: The overall incision infection rate was 38.4% (92 of 239): 61 patients (50.8%) had an infection in the 30% FiO2 group and 31 (26%) in the 80% FiO2 group (p < 0.05). The risk of SSI was 48% lower in the 80% FiO2 group (relative risk 0.51; 95% confidence interval [CI] 0.28-1.08) vs 30% FiO2. CONCLUSIONS: Supplemental 80% FiO2 during and for 6 h after open surgery for PPU, which reduces post-operative SSI, should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost. PMID- 26554854 TI - Optimization of MRI-based scoring scales of brain injury severity in children with unilateral cerebral palsy. AB - BACKGROUND: Several scoring systems for measuring brain injury severity have been developed to standardize the classification of MRI results, which allows for the prediction of functional outcomes to help plan effective interventions for children with cerebral palsy. OBJECTIVE: The aim of this study is to use statistical techniques to optimize the clinical utility of a recently proposed template-based scoring method by weighting individual anatomical scores of injury, while maintaining its simplicity by retaining only a subset of scored anatomical regions. MATERIALS AND METHODS: Seventy-six children with unilateral cerebral palsy were evaluated in terms of upper limb motor function using the Assisting Hand Assessment measure and injuries visible on MRI using a semiquantitative approach. This cohort included 52 children with periventricular white matter injury and 24 with cortical and deep gray matter injuries. A subset of the template-derived cerebral regions was selected using a data-driven region selection algorithm. Linear regression was performed using this subset, with interaction effects excluded. RESULTS: Linear regression improved multiple correlations between MRI-based and Assisting Hand Assessment scores for both periventricular white matter (R squared increased to 0.45 from 0, P < 0.0001) and cortical and deep gray matter (0.84 from 0.44, P < 0.0001) cohorts. In both cohorts, the data-driven approach retained fewer than 8 of the 40 template derived anatomical regions. CONCLUSION: The equal or better prediction of the clinically meaningful Assisting Hand Assessment measure using fewer anatomical regions highlights the potential of these developments to enable enhanced quantification of injury and prediction of patient motor outcome, while maintaining the clinical expediency of the scoring approach. PMID- 26554856 TI - Sponge-like nanoporous single crystals of gold. AB - Single crystals in nature often demonstrate fascinating intricate porous morphologies rather than classical faceted surfaces. We attempt to grow such crystals, drawing inspiration from biogenic porous single crystals. Here we show that nanoporous single crystals of gold can be grown with no need for any elaborate fabrication steps. These crystals are found to grow following solidification of a eutectic composition melt that forms as a result of the dewetting of nanometric thin films. We also present a kinetic model that shows how this nano-porous single-crystalline structure can be obtained, and which allows the potential size of the porous single crystal to be predicted. Retaining their single-crystalline nature is due to the fact that the full crystallization process is faster than the average period between two subsequent nucleation events. Our findings clearly demonstrate that it is possible to form single crystalline nano porous metal crystals in a controlled manner. PMID- 26554855 TI - Ultrasound-guided fine-needle aspiration biopsy of pediatric thyroid nodules. AB - BACKGROUND: The role of US-guided fine-needle aspiration biopsy (US-FNAB) of thyroid nodules is not well-established in children. OBJECTIVE: To retrospectively assess the utility of US-FNAB of pediatric thyroid nodules. MATERIALS AND METHODS: We reviewed Department of Radiology records to identify children who underwent US-FNAB of the thyroid between 2005 and 2013. Two board certified pediatric radiologists reviewed pre-procedural thyroid US exams and documented findings by consensus. We recorded cytopathology findings and compared them to surgical pathology diagnoses if the nodule was resected. We also recorded demographic information, use of sedation or general anesthesia, and presence of on-site cytopathological feedback. The Student's t-test was used to compare continuous data; the Fisher exact test was used to compare proportions. RESULTS: US-FNAB was conducted on a total of 86 thyroid nodules in 70 children; 56 were girls (80%). Seventy-eight of the 86 (90.7%) US-FNAB procedures were diagnostic; 69/78 (88.5%) diagnostic specimens were benign (including six indeterminate follicular lesions that were proved at surgery to be benign) and 9/78 (11.5%) were malignant/suspicious for malignancy (all proved to be papillary carcinomas). There was no difference in size of benign vs. malignant lesions (P = 0.82) or diagnostic vs. non-diagnostic lesions (P = 0.87). Gender (P = 0.19), use of sedation/general anesthesia (P = 0.99), and presence of onsite cytopathological feedback (P = 0.99) did not affect diagnostic adequacy. Microcalcifications (P < 0.0001; odds ratio [OR] = 113.7) and coarse calcifications (P = 0.03; OR = 19.4) were associated with malignancy. Diagnoses at cytopathology and surgical pathology were concordant in 27/29 (93.1%) nodules; no US-FNAB procedure yielded false-positive or false-negative results for malignancy. CONCLUSION: US-FNAB of pediatric thyroid nodules is feasible, allows diagnostic cytopathological evaluation, and correlates with surgical pathology results in resected nodules. PMID- 26554857 TI - Evaluation of Adenovirus-Mediated Down-Regulation of Connective Tissue Growth Factor on Postoperative Wound Healing After Experimental Glaucoma Surgery. AB - PURPOSE: This study was aimed to determine whether adenovirus-mediated down regulation of connective tissue growth factor (CTGF) can modulate postoperative scarring in a rabbit receiving simplified glaucoma surgery. METHODS: In vitro studies were performed using a replication-deficient recombinant adenovirus that transcribes a small interfering RNA (siRNA) specific to the CTGF gene under the control of the modified CMV promoter. Primary tenon cells from a New Zealand White rabbit were transduced with 10-100 plaque-forming units (pfu) per cell of the viral vector. Seventy-two hours later, CTGF expression was analyzed by Western blot analysis. In vivo studies were conducted using 10 New Zealand White rabbits, which underwent simplified glaucoma surgery and received a postoperative subconjunctival injection of 5 ul suspension of adenovirus carrying shRNA for CTGF (2 * 10(11) pfu/ml) in the right eye, and the same amount of null virus in the left eye. Eyes were enucleated 5 d after the surgery, and immunohistochemical and histological examinations of the surgical outcome were performed. RESULTS: Western blot analysis showed that CTGF was depleted to less than 10% of its original level in cells transduced with the adenovirus expressing CTGF-specific siRNA. This demonstrates RNA interference (RNAi)-mediated CTGF inactivation in vitro. Immunohistochemical analysis also showed that CTGF was significantly depleted in eyes transduced with the adenovirus expressing CTGF siRNA. This demonstrates RNAi-mediated CTGF inactivation in vivo. In addition, less scar tissue was observed on histological evaluation in the transduced eyes, demonstrating that inhibition of CTGF expression can modulate the wound healing process after surgery. CONCLUSIONS: Down-regulation of CTGF is effective in inhibiting postoperative scarring in vivo. This suggests that RNAi with CTGF siRNA may potentially pave the road for a novel therapeutic strategy to improve glaucoma surgery results. PMID- 26554858 TI - Flow Analysis of Amino Acids by Using a Newly Developed Aminoacyl-tRNA Synthetase Immobilized, Small Reactor Column-Based Assay. AB - Abnormal concentrations of amino acids in blood and urine can be indicative of several diseases, including cancer and diabetes. Therefore, analyses that examine amino acid concentrations are useful for the diagnosis of such diseases. In this study, we developed an enzyme-immobilized, small reactor column for flow analysis of amino acid concentrations. For the recognition of asparagine and lysine, asparaginyl-tRNA synthetase and lysyl-tRNA synthase were immobilized onto microparticles, respectively, and coupled with coloration reagents for spectrophotometric detection. This assay has some advantages in the analytical field, such as the ability to detect small amounts of analyte, allowing for the use of a small reaction volume, and ensuring a rapid and efficient reaction rate. This approach provided selective quantitation of up to 480 MUM of asparagine and lysine in 200 mM Tris-HCl buffer (pH 8.0). PMID- 26554859 TI - Levels of physical activity, motivation and barriers to participation in university students. AB - BACKGROUND: Grounded in self-determination theory and trans-theoretical model applied to exercise, the aim of this study was to analyse the existing relationships between physical activity (PA) carried out by university students, perceived barriers to PA, motivation to PA and stages of change. METHODS: 901 Spanish students took part in the study (408 men, 493 women; mean age 22.59+/ 3.59), who completed the Behavioural Regulation in Exercise Questionnaire (BREQ 3), Scale of Barriers to PA, Stages of Change and the International Physical Activity Questionnaire - Short Form (IPAQ-SF). RESULTS: Noteworthy among the findings is the positive relationship between the more autonomous regulation forms, especially integrated regulation, and the moderate to vigorous PA (MVPA) levels. However, barriers to participatrion are negatively related to PA levels and the more self-determined forms of motivation. Finally, students in action and maintenance stages, and those who comply with the recommendations on PA present higher values in the more self-determined motivation forms and lower values in barriers to participation in PA. CONCLUSIONS: The study shows the importance of addressing the analysis of variables associated with engagement in PA in the university population to develop healthy policies and intervention programmes that can establish a series of healthy and more active habits in the youth-adult stage. The appropriateness of promoting more self-determined motivation forms is highlighted, especially integrated regulation, to have an impact on higher levels of MVPA. PMID- 26554860 TI - New score based on early repolarization in precordial leads for detection of left ventricular hypertrophy in young soccer players. PMID- 26554861 TI - Polydimethylsiloxane films doped with NdFeB powder: magnetic characterization and potential applications in biomedical engineering and microrobotics. AB - This work reports the fabrication, magnetic characterization and controlled navigation of film-shaped microrobots consisting of a polydimethylsiloxane-NdFeB powder composite material. The fabrication process relies on spin-coating deposition, powder orientation and permanent magnetization. Films with different powder concentrations (10 %, 30 %, 50 % and 70 % w/w) were fabricated and characterized in terms of magnetic properties and magnetic navigation performances (by exploiting an electromagnet-based platform). Standardized data are provided, thus enabling the exploitation of these composite materials in a wide range of applications, from MEMS/microrobot development to biomedical systems. Finally, the possibility to microfabricate free-standing polymeric structures and the biocompatibility of the proposed composite materials is demonstrated. PMID- 26554862 TI - Clinical, Hematological and Molecular Analysis of Homozygous Hb E (HBB: c.79G > A) in the Indian Population. AB - Homozygous Hb E [beta26(B8)Glu->Lys; HBB: c.79G > A] is a clinically mild disease with no significant symptoms. Very few studies are available on clinical variability in Hb E disorders. We report the profile of a series of homozygous Hb E patients in the Indian population. We analyzed various genetic factors that contribute to the heterogeneity in the phenotype of homozygous Hb E patients. Analysis of these parameters further enhances our understanding of the Hb E syndrome. PMID- 26554863 TI - Molecular determinants of chemotherapy resistance in ovarian cancer. PMID- 26554864 TI - Testudinibacter aquarius gen. nov., sp. nov., a member of the family Pasteurellaceae isolated from the oral cavity of freshwater turtles. AB - A total of 13 Pasteurellaceae isolates from healthy freshwater turtles were characterized by genotypic and phenotypic tests. Phylogenetic analysis of partial 16S rRNA and rpoB gene sequences showed that the isolates investigated formed a monophyletic group. The closest related species based on 16S rRNA gene sequencing was Chelonobacter oris CCUG 55632T with 94.4 % similarity and the closest related species based on rpoB gene sequence comparison was [Pasteurella] testudinis CCUG 19802T with 91.5 % similarity. All the investigated isolates exhibited phenotypic characteristics of the family Pasteurellaceae. However, they could be separated from existing genera of the Pasteurellaceae by the following test results: indole, ornithine decarboxylase and Voges-Proskauer positive; and methyl red, urease and PNPG (alpha-glucosidase) negative. No X- or V-factor requirement was observed. A zone of beta-haemolysis surrounded the colonies after 24 h of incubation on bovine blood agar at 37 degrees C. Acid was produced from l arabinose, dulcitol, d-mannitol, sucrose and trehalose. Representative strain ELNT2xT had a fatty acid profile that was characteristic for members of the Pasteurellaceae. ELNT2xT expressed only one respiratory quinone, ubiquinone-8 (100 %). The DNA G+C content of strain ELNT2xT was 42.8 mol%. On the basis of both phylogenetic and phenotypic evidence, it is proposed that the strains should be classified as representatives of a novel species of a new genus, Testudinibacter aquarius gen. nov., sp. nov. The type strain of Testudinibacter aquarius is ELNT2xT ( = CCUG 65146T = DSM 28140T), which was isolated from the oral cavity of a captive eastern long-necked turtle (Chelodina longicollis) in Denmark in 2012. PMID- 26554865 TI - Waiting for an Answer: Hospice Care and Novel Immunotherapy. PMID- 26554866 TI - MiR-506 functions as a tumor suppressor in glioma by targeting STAT3. AB - MicroRNA-506 (miR-506) has been reported to act as a tumor suppressive or an oncogenic miRNA in different types of tumors. However, the roles and underlying molecular mechanism of miR-506 in glioma remain unclear. In the present study, we performed quantitative PCR to investigate the level of miR-506 in 36 pairs of glioma tumor and matched adjacent tissues, and found that miR-506 was downregulated in the glioma tumors compared to the expression in the adjacent normal tissues. Furthermore, a functional assay found that ectopic expression of miR-506 in glioma cells markedly suppressed cell proliferation, colony formation, migration and invasion, and suppressed tumor growth in vivo. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-506. Western blot assay showed that overexpression of miR-506 not only induced changes in STAT3 expression but also altered expression of its downstream genes, including, Bcl2, cyclin D1 and matrix metalloproteinase 2 (MMP 2), in the human glioma cells. In addition, STAT3 mRNA expression was increased in the glioma tissues, and was inversely correlated with miR-506. Importantly, overexpression of STAT3 in glioma cells attenuated the suppressive effects of miR 506 on cell proliferation, colony formation, migration and invasion. These results showed that miR-506 functions as a tumor suppressor in glioma by targeting STAT3, suggesting that miR-506 may serve as a potential target in the treatment of human glioma. PMID- 26554867 TI - A regulatory gene network related to the porcine umami taste receptor (TAS1R1/TAS1R3). AB - Taste perception plays an important role in the mediation of food choices in mammals. The first porcine taste receptor genes identified, sequenced and characterized, TAS1R1 and TAS1R3, were related to the dimeric receptor for umami taste. However, little is known about their regulatory network. The objective of this study was to unfold the genetic network involved in porcine umami taste perception. We performed a meta-analysis of 20 gene expression studies spanning 480 porcine microarray chips and screened 328 taste-related genes by selective mining steps among the available 12,320 genes. A porcine umami taste-specific regulatory network was constructed based on the normalized coexpression data of the 328 genes across 27 tissues. From the network, we revealed the 'taste module' and identified a coexpression cluster for the umami taste according to the first connector with the TAS1R1/TAS1R3 genes. Our findings identify several taste related regulatory genes and extend previous genetic background of porcine umami taste. PMID- 26554868 TI - Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen. AB - We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity. PMID- 26554869 TI - Link Between Positive Clinician-Conveyed Expectations of Treatment Effect and Pain Reduction in Knee Osteoarthritis, Mediated by Patient Self-Efficacy. AB - OBJECTIVE: A prior knee osteoarthritis (OA) trial found that provider-conveyed expectations for treatment success were associated with pain improvement. We hypothesized this relationship was mediated by patient self-efficacy, since expectations of improvement may enhance one's ability to control health behaviors, and therefore health. Our aim was to examine whether self-efficacy was a mediator of the relationship observed in this trial. METHODS: A secondary analysis of a 3-arm (traditional acupuncture, sham acupuncture, and wait list) trial for knee OA was conducted. Those in the acupuncture groups were equally randomized to acupuncturists trained to communicate a high or neutral expectation of treatment success (e.g., using language conveying high or unclear likelihood that acupuncture would reduce knee pain). A modified Arthritis Self-Efficacy Questionnaire and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale were administered. Linear regression analyses were used to examine whether patient self-efficacy mediated the relationship between provider communication style and knee pain at 3 months. RESULTS: High-expectation provider communication was associated with patient self-efficacy, beta coefficient of 0.14 (95% confidence interval [95% CI] 0.01, 0.28). Self-efficacy was associated with WOMAC pain, beta coefficient of -9.29 (95% CI -11.11, -7.47), while controlling for the provider communication style. The indirect effect a * b of -1.36 for high versus neutral expectation (bootstrap 95% CI -2.80, -0.15; does not include 0), supports the conclusion that patient self-efficacy mediates the relationship between provider-communicated expectations of treatment effects and knee pain. CONCLUSION: Our findings suggest that clinician-conveyed expectations can enhance the benefit of treatments targeting knee OA symptoms, mediated by improved patient self-efficacy. PMID- 26554870 TI - Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles. AB - Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe3O4) nanoparticles followed by high-speed emulsification to form a poly(lactic-co glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering. PMID- 26554871 TI - Congenital thrombocytopenia in a neonate with an interstitial microdeletion of 3q26.2q26.31. AB - Interstitial deletions encompassing the 3q26.2 region are rare. Only one case report was published this far describing a patient with an interstitial deletion of 3q26.2 (involving the MDS1-EVI1 complex (MECOM)) and congenital thrombocytopenia. In this report we describe a case of a neonate with congenital thrombocytopenia and a constitutional 4.52 Mb deletion of 3q26.2q26.31 including TERC and the first 2 exons of MECOM, involving MDS1 but not EVI1. The deletion was demonstrated by array-CGH on lymphocytes. Our report confirms that congenital thrombocytopenia can be due to a constitutional deletion of 3q26.2 involving MECOM. We suggest that in case of unexplained neonatal thrombocytopenia, with even just slight facial dysmorphism, DNA microarray on peripheral blood should be considered early in the diagnostic work-up. PMID- 26554872 TI - Identifying Different Types of Catalysts for CO2 Reduction by Ethane through Dry Reforming and Oxidative Dehydrogenation. AB - The recent shale gas boom combined with the requirement to reduce atmospheric CO2 have created an opportunity for using both raw materials (shale gas and CO2 ) in a single process. Shale gas is primarily made up of methane, but ethane comprises about 10 % and reserves are underutilized. Two routes have been investigated by combining ethane decomposition with CO2 reduction to produce products of higher value. The first reaction is ethane dry reforming which produces synthesis gas (CO+H2 ). The second route is oxidative dehydrogenation which produces ethylene using CO2 as a soft oxidant. The results of this study indicate that the Pt/CeO2 catalyst shows promise for the production of synthesis gas, while Mo2 C-based materials preserve the C?C bond of ethane to produce ethylene. These findings are supported by density functional theory (DFT) calculations and X-ray absorption near-edge spectroscopy (XANES) characterization of the catalysts under in situ reaction conditions. PMID- 26554873 TI - Acculturation and Intention to Breastfeed among a Population of Predominantly Puerto Rican Women. AB - BACKGROUND: Latinas have high overall breastfeeding initiation rates, yet Puerto Ricans have among the lowest exclusive breastfeeding rates. This study sought to determine if acculturation was associated with intent to breastfeed in a predominantly Puerto Rican population. METHODS: A cohort of Latina women were enrolled in Proyecto Buena Salud, and provided information on infant feeding intent (n = 1,323). Acculturation was assessed via the Psychological Acculturation Scale (PAS), language preference, and generation in the United States. RESULTS: Increasing acculturation as measured by English language preference (aOR 0.61 [95% CI 0.42-0.88]) and second or third generation in the United States (aOR 0.70 [95% CI 0.52-0.95)] was inversely associated with odds of intending to exclusively breastfeed. Similarly, women with higher levels of acculturation as measured by the PAS (aOR 0.67 [95% CI 0.45-0.99]), English language preference (aOR 0.48 [95% CI 0.33-0.70]) and second or third generation in the United States (aOR 0.42 [95% CI 0.31-0.58]) were less likely to report intent to combination feed as compared with women with lower acculturation. CONCLUSIONS: Acculturation was inversely associated with intent to exclusively breastfeed and intent to combination feed in this predominantly Puerto Rican sample. PMID- 26554874 TI - Regulatory anticipation of postmarket safety problems for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study. AB - PURPOSE: The aim of the study is to describe preapproval safety concerns expressed by the European Medicines Agency (EMA) following regulatory review and to compare those concerns with subsequent issuance of postmarket safety communications. METHODS: All novel medicines approved by the EMA through the centralized authorization procedure from 2001 to 2010 were included. Preapproval safety concerns were identified through examination of information related to regulatory review publicly available on the EMA's website. Relevant postmarket safety events were identified through Dear Healthcare Professional Communications (DHPCs), including those resulting in a withdrawal, issued by at least one of four leading national regulators of the European Union. RESULTS: Among the 184 novel medicines included, the EMA had expressed at least one preapproval safety concern for 110 (59.8%) of them. Then, at least one safety communication was issued for 53 (28.8%) medicines within the postmarket period of study, totaling 90 DHPCs and 5 withdrawals. Overall, these 95 DHPCs and withdrawals were pertaining to 66 different clinical safety events. The EMA had expressed a preapproval concern consistent with the postmarket safety event for 22.7% (15 of 66). The rate of issuance of a postmarket safety communication was not statistically different between medicines with or without any preapproval safety concern (31.8% vs. 24%, p = 0.25). CONCLUSIONS: Preapproval safety concerns are frequently expressed by the EMA following regulatory review. However, when comparing postmarket safety communications with prior concerns, anticipation was low. Our findings emphasize the need to systematically conduct postmarket studies dedicated to safety evaluation. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26554875 TI - Role and mechanism of insulin-like growth factor 2 on the proliferation of human trophoblasts in vitro. AB - AIM: To study the effect and relevant molecular mechanisms of insulin-like growth factor 2 (IGF2) on the proliferative activity of first trimester human trophoblasts in vitro. MATERIALS AND METHODS: Extravillous cytotrophoblasts (EVCTs) were isolated and cultured. Cells were cultured with IGF2 at different concentrations and the proliferative activity was measured using methyl thiazolyl tretrazolium assay. LY294002, a specific inhibitor of the phosphatidylinositol 3 kinase (PI3K), was used as an indirect indicator of the possible involvement of the PI3K signal pathway. We tested the apoptosis rate using flow cytometry technology influenced by IGF2 with or without LY294002. The effects of IGF2 on phosphorylation of key cell signaling proteins (protein kinase B [AKT] and phosphorylated AKT) in EVCTs were examined by western blot analysis with or without LY294002. RESULTS: There was a significant difference between the IGF2 group above 10 nM and the control group (P < 0.05). LY294002 (10 MUM) not only inhibited the proliferative activity of EVCT, but also significantly restrained the effect on EVCTs (P < 0.05). In vitro data proved that the apoptosis rate decreased when IGF2 was added (P < 0.05), but increased when inhibited by LY294002 (P < 0.05). After incubation with IGF2, AKT phosphorylation increased compared to incubation without IGF2 treatment (P < 0.05). LY294002 activation reduced the IGF2-induced effects (P < 0.05). CONCLUSIONS: Our data suggest that IGF2 enhances EVCT proliferation and inhibits apoptosis. The PI3K/AKT pathway is an important signaling pathway in the proliferative activity of EVCTs on early human pregnancy in vitro. PMID- 26554876 TI - When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious Adverse Joint Events in the Tanezumab Clinical Development Program. AB - OBJECTIVE: Tanezumab, a monoclonal antibody against nerve growth factor, has demonstrated efficacy in clinical trials of chronic pain in osteoarthritis (OA) and chronic low back pain. Unexpected adverse events (AEs) described as osteonecrosis (ON) occurred during tanezumab development, leading the US Food and Drug Administration to impose a partial clinical hold for all indications except cancer pain. A blinded Adjudication Committee (AC) including orthopedic surgeons, rheumatologists, and an orthopedic pathologist reviewed and adjudicated joint related AEs in the tanezumab clinical program. METHODS: The AC adjudicated all reported cases of ON as well as cases of total joint replacements (TJRs) not reported as ON for which radiographs obtained within 9 months of the surgery were available. The AC prespecified categories for joint safety events including primary ON, worsening OA (rapid progression of OA [RPOA], normal progression of OA, insufficient information to distinguish between rapid and normal progression of OA), other, or insufficient information to distinguish between primary ON and worsening OA or another diagnosis. RESULTS: The AC reviewed events in 249 of 386 patients with an investigator-reported AE of ON and/or a TJR. Two events were adjudicated as primary ON, 200 events were adjudicated as worsening OA (68 of which were classified as RPOA), 29 events had another diagnosis, 11 had insufficient information to distinguish primary ON from worsening OA, and 7 did not have committee member consensus. CONCLUSION: Despite initial reports, tanezumab treatment was not associated with an increase in ON but was associated with an increase in RPOA. Higher doses of tanezumab, tanezumab administered with nonsteroidal antiinflammatory drugs, and preexisting subchondral insufficiency fractures were risk factors for RPOA in this cohort. PMID- 26554877 TI - Climate change and larval transport in the ocean: fractional effects from physical and physiological factors. AB - Changes in larval import, export, and self-seeding will affect the resilience of coral reef ecosystems. Climate change will alter the ocean currents that transport larvae and also increase sea surface temperatures (SST), hastening development, and shortening larval durations. Here, we use transport simulations to estimate future larval connectivity due to: (1) physical transport of larvae from altered circulation alone, and (2) the combined effects of altered currents plus physiological response to warming. Virtual larvae from islands throughout Micronesia were moved according to present-day and future ocean circulation models. The Hybrid Coordinate Ocean Model (HYCOM) spanning 2004-2012 represented present-day currents. For future currents, we altered HYCOM using analysis from the National Center for Atmospheric Research Community Earth System Model, version 1-Biogeochemistry, Representative Concentration Pathway 8.5 experiment. Based on the NCAR model, regional SST is estimated to rise 2.74 degrees C which corresponds to a ~17% decline in larval duration for some taxa. This reduction was the basis for a separate set of simulations. Results predict an increase in self-seeding in 100 years such that 62-76% of islands experienced increased self seeding, there was an average domainwide increase of ~1-3% points in self seeding, and increases of up to 25% points for several individual islands. When changed currents alone were considered, approximately half (i.e., random) of all island pairs experienced decreased connectivity but when reduced PLD was added as an effect, ~65% of connections were weakened. Orientation of archipelagos relative to currents determined the directional bias in connectivity changes. There was no universal relationship between climate change and connectivity applicable to all taxa and settings. Islands that presently export large numbers of larvae but that also maintain or enhance this role into the future should be the focus of conservation measures that promote long-term resilience of larval supply. PMID- 26554878 TI - Transparency in a Pediatric Quality Improvement Collaborative: A Passionate Journey by NPC-QIC Clinicians and Parents. AB - Transparency-sharing data or information about outcomes, processes, protocols, and practices-may be the most powerful driver of health care improvement. In this special article, the development and growth of transparency within the National Pediatric Cardiology Quality Improvement Collaborative is described. The National Pediatric Cardiology Quality Improvement Collaborative transparency journey is guided by equal numbers of clinicians and parents of children with congenital heart disease working together in a Transparency Work Group. Activities are organized around four interrelated levels of transparency (individual, organizational, collaborative, and system), each with a specified purpose and aim. A number of Transparency Work Group recommendations have been operationalized. Aggregate collaborative performance is now reported on the public-facing web site. Specific information that the Transparency Work Group recommends centers provide to parents has been developed and published. Almost half of National Pediatric Cardiology Quality Improvement Collaborative centers participated in a pilot of transparently sharing their outcomes achieved with one another. Individual centers have also begun successfully implementing recommended transparency activities. Despite progress, barriers to full transparency persist, including health care organization concerns about potential negative effects of disclosure on reputation and finances, and lack of reliable definitions, data, and reporting standards for fair comparisons of centers. The National Pediatric Cardiology Quality Improvement Collaborative's transparency efforts have been a journey that continues, not a single goal or destination. Balanced participation of clinicians and parents has been a critical element of the collaborative's success on this issue. Plans are in place to guide implementation of additional transparency recommendations across all four levels, including extension of the activities beyond the collaborative to support transparency efforts in national cardiology and cardiac surgery societies. PMID- 26554879 TI - Genotype distribution characteristics of high-risk human papillomaviruses in women from Shanghai, China. AB - High-risk human papillomaviruses (HPVs) are highly prevalent worldwide, and HPV genotype distribution varies regionally. Molecular surveys of HPVs are important for effective HPV control and prevention. Fifteen high-risk HPV strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and six low-risk HPV strains (HPV6, 11, 42, 43, 44, CP8304) were detected by cervical cytology from 10 501 subjects. High-risk HPVs, low-risk HPVs, and both high- and low-risk HPVs were detected in 14.5%, 2.8%, and 2.4% of cases, respectively. Of 1782 subjects with high-risk HPV infection, 75.5%, 18.1%, and 6.4% were infected with one, two, and ?3 strains of high-risk HPVs, respectively. HPV52, HPV16, and HPV58 were the top three most dominant high-risk HPV genotypes in our population with positivity rates of 23.0%, 17.7% and 16.9%, respectively. Multiple infection was common, with significantly higher co-infection rates of HPV58/HPV33 (12.9%) and HPV58/HPV52 (11.3%). Further data comparisons showed that HPV genotype distribution varied markedly between domestic and international regions. In conclusion, a monolithic vaccination strategy is obviously impractical, and regional HPV surveillance is essential to optimize current HPV control and prevention. PMID- 26554880 TI - The Italian genome reflects the history of Europe and the Mediterranean basin. AB - Recent scientific literature has highlighted the relevance of population genetic studies both for disease association mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of the Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single-nucleotide polymorphisms in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which have produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population's ancestry, identifying the genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., 'barbarian invasion' of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe. PMID- 26554881 TI - Big Data in medical research and EU data protection law: challenges to the consent or anonymise approach. AB - Medical research is increasingly becoming data-intensive; sensitive data are being re-used, linked and analysed on an unprecedented scale. The current EU data protection law reform has led to an intense debate about its potential effect on this processing of data in medical research. To contribute to this evolving debate, this paper reviews how the dominant 'consent or anonymise approach' is challenged in a data-intensive medical research context, and discusses possible ways forwards within the EU legal framework on data protection. A large part of the debate in literature focuses on the acceptability of adapting consent or anonymisation mechanisms to overcome the challenges within these approaches. We however believe that the search for ways forward within the consent or anonymise paradigm will become increasingly difficult. Therefore, we underline the necessity of an appropriate research exemption from consent for the use of sensitive personal data in medical research to take account of all legitimate interests. The appropriate conditions of such a research exemption are however subject to debate, and we expect that there will be minimal harmonisation of these conditions in the forthcoming EU Data Protection Regulation. Further deliberation is required to determine when a shift away from consent as a legal basis is necessary and proportional in a data-intensive medical research context, and what safeguards should be put in place when such a research exemption from consent is provided. PMID- 26554882 TI - Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology. AB - Red blood cell counts have been proven to be one of the most frequently performed blood tests and are valuable for early diagnosis of some diseases. This paper describes an automated red blood cell counting method based on microscopic hyperspectral imaging technology. Unlike the light microscopy-based red blood count methods, a combined spatial and spectral algorithm is proposed to identify red blood cells by integrating active contour models and automated two dimensional k-means with spectral angle mapper algorithm. Experimental results show that the proposed algorithm has better performance than spatial based algorithm because the new algorithm can jointly use the spatial and spectral information of blood cells. PMID- 26554883 TI - Effect of intravaginal dehydroepiandrosterone treatment on the endometrium: should androstenediol be a concern? PMID- 26554884 TI - Effect of isolated vitamin D supplementation on the rate of falls and postural balance in postmenopausal women fallers: a randomized, double-blind, placebo controlled trial. AB - OBJECTIVE: To evaluate the effect of isolated vitamin D supplementation (VITD) on the rate of falls and postural balance in postmenopausal women fallers. METHODS: In this double-blind, placebo-controlled trial, 160 Brazilian younger postmenopausal women were randomized into two groups: VITD group, vitamin D3 supplementation 1,000 IU/day/orally (n = 80) and placebo group (n = 80). Women with amenorrhea at least 12 months, age 50 to 65 years, and a history of falls (previous 12 months) were included. Those with neurological or musculoskeletal disorders, vestibulopathies, drugs use that could affect balance and osteoporosis were excluded. The intervention time was 9 months. Postural balance was assessed by stabilometry (computerized force platform) and investigation on the occurrence/recurrence of falls was performed by interviews. The plasma concentration of 25-hydroxyvitamin D [25(OH)D] was measured by high-performance liquid chromatography. Statistical analysis was achieved by intention-to-treat, using analysis of variance, Student's t test, Tukey test, chi-square, and logistic regression. RESULTS: After 9 months, mean values of 25(OH)D increased from 15.0 +/- 7.5 ng/mL to 27.5 +/- 10.4 ng/mL (+45.4%) in the VITD group, and decreased from 16.9 +/- 6.7 ng/mL to 13.8 +/- 6.0 ng/mL (-18.5%) in the placebo group (P < 0.001). The occurrence of falls was higher in the placebo group (+46.3%) with an adjusted risk of 1.95 (95% confidence interval [CI] 1.23-3.08) times more likely to fall and 2.80 (95% CI 1.43-5.50) times higher for recurrent falls compared to the VITD group (P < 0.001). There was reduction in body sway by stabilometry, with lower amplitude of antero-posterior (-35.5%) and latero lateral (-37.0%) oscillation, only in the VITD group (P < 0.001). CONCLUSIONS: In Brazilian postmenopausal women fallers, isolated vitamin D supplementation for 9 months resulted in a lower incidence of falls and improvement in postural balance. PMID- 26554885 TI - How I diagnose and treat neutropenia. AB - PURPOSE OF REVIEW: Neutropenia absolute neutrophil count (ANC) less than 1.5 * 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 * 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). RECENT FINDINGS: Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated. SUMMARY: The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF. PMID- 26554886 TI - Update on biosimilars of granulocyte colony-stimulating factor - when no news is good news. AB - PURPOSE OF REVIEW: With the approval of the first biosimilar granulocyte colony stimulating factor (G-CSF), biosimilars - copies of therapeutic biologicals whose patent protection has expired - have finally reached the US healthcare market. Its advent is an occasion for a closer look at recent insights into biosimilar G CSF and an attempt at prognosticating the future (future role) of biosimilars in general. RECENT FINDINGS: Recent literature regarding biosimilar G-CSF orbits significantly around patient access and effects on healthcare expenditure. The advent of biosimilar G-CSF has induced unexpectedly large price reductions for short-acting G-CSF. On the clinical side, little excitement is tangible, probably appropriately so, since clinical data indicate nothing short of biological similarity. Although formal clinical trials are few, the plethora of case series and historic comparisons which have come forth offer reassurance about the appropriateness of the regulators' assessment of biosimilar G-CSF as indeed in all respects biologically similar to the originator. SUMMARY: All evidence points to an overwhelming similarity of originator and biosimilar G-CSF in all indications. Overall clinical acceptance, albeit possibly significantly dictated by economic pressures, is good. Price reductions exceed predictions and may jeopardize the economic viability of biosimilar programs. A concurrent shift towards long-acting G-CSF ('biobetters') is observed in Europe. PMID- 26554887 TI - Interferon regulatory factor 8 and the regulation of neutrophil, monocyte, and dendritic cell production. AB - PURPOSE OF REVIEW: Interferon regulatory factor 8 (IRF8) is a transcription factor that plays central roles in the regulation of myeloid cell fate. In both mice and humans, IRF8 is required for the differentiation of most monocyte and dendritic cell subsets, but suppresses neutrophil production. IRF8 mutations can cause immunodeficiency, and the dysregulated differentiation that underlies myeloid leukemia has been attributed in part to reduced IRF8 expression. In this review we discuss recent studies that have revealed molecular mechanisms underlying the regulation of myelopoiesis by IRF8, which cooperates with other transcription factors to control the initiation of gene expression programs that define the development of specific myeloid cell subsets. RECENT FINDINGS: It is now clear that IRF8 regulates cell fate choice by both promoting monocyte/dendritic cell differentiation and suppressing neutrophil differentiation. Recent studies have shown that it collaborates with PU.1 to promote monocyte gene expression (in part via induction of Kruppel-like factor 4), associates with Batf3 to induce CD8alpha conventional dendritic cell differentiation via autoregulation of its own expression, and restricts neutrophil gene expression by disrupting the binding of c/EBPalpha to target genes. SUMMARY: These studies have emphasized the importance of IRF8 in the regulation of myelopoiesis and are revealing novel therapeutic targets. PMID- 26554888 TI - Unexpected role of inflammatory signaling in hematopoietic stem cell development: its role beyond inflammation. AB - PURPOSE OF REVIEW: Inflammatory signaling under pathological conditions like infection and inflammation has been extensively studied. Whether inflammatory signaling plays a role in physiology and development remains elusive. The review summarizes recent advances in inflammatory signaling with particular focus on how distinct inflammatory signaling regulates hematopoietic stem cell (HSC) development. Understanding the underlying mechanism of inflammatory signaling on HSC development may help to generate and/or expand a large number of functional HSCs for clinical application. RECENT FINDINGS: Like the hematopoietic progenitors, HSCs can be the first responders to infection. An unexpected observation is that genes involved in innate immunity and inflammatory signaling are enriched in emerging HSCs and their niche during embryogenesis. Thus, inflammatory signaling may also play a role in HSC development in the absence of infection and inflammation. SUMMARY: Inflammatory signaling is not only an important regulator of HSCs in response to infection, but also plays a previously unrecognized role in HSC development in the absence of infection and inflammation. The baseline inflammatory signaling can be activated to promote HSC development in cell autonomous and noncell autonomous manners. However, direct response of HSCs to inflammatory stimuli is not always advantageous and excessive chronic signaling can have negative effects on HSC regulation and function. PMID- 26554889 TI - Plerixafor for stem cell mobilization: the current status. AB - PURPOSE OF REVIEW: Nowadays, plerixafor is approved for patients who fail to mobilize sufficient CD34+ cells for an autologous stem cell transplantation. Plerixafor is effective in the majority of these patients, who otherwise could not be treated adequately. We discussed in this review the current status of the optimal use of plerixafor in different clinical diagnoses and settings. RECENT FINDINGS: Plerixafor seems to be more effective in patients with multiple myeloma than in lymphoma. Even patients who had very low circulating CD34+ cells before administration of plerixafor have an important benefit. Several strategies in different clinical settings showed an effective response after administration of plerixafor, without the superiority of one strategy. Plerixafor is well tolerated with acceptable toxicity; however, it is an expensive drug. SUMMARY: Plerixafor is an effective drug in patients who fail to mobilize with conventional strategy. No strategy seems superior for the optimal use of plerixafor. More studies focusing on the kinetics and cost-effectiveness are needed. PMID- 26554890 TI - Update on granulocyte transfusions: accumulation of promising data, but still lack of decisive evidence. AB - PURPOSE OF REVIEW: Inconsistent results regarding the clinical efficacy of granulocyte transfusions for the treatment or prophylaxis of life-threatening infections in neutropenic patients have been attributed to insufficient number of transfused neutrophils. Since the introduction of granulocyte colony-stimulating factor (G-CSF) to the granulocyte mobilization regimen in the 1990s, the number of transfused cells significantly increased, which directly translated to a significant increase in absolute neutrophil counts in the transfused patients. RECENT FINDINGS: For therapeutic granulocyte transfusions, neither of the two randomized controlled studies in the G-CSF era could demonstrate a clear clinical benefit. However, a number of small studies or case series have suggested its clinical efficacy, including one that demonstrated the clinical response against drug-resistant invasive fusariosis. For prophylactic granulocyte transfusions, there have been scarce reports in the G-CSF era. A pulmonary reaction is the most significant adverse event after granulocyte transfusions, although its reported frequency varies among studies. SUMMARY: Despite the expectation that the increased number of transfused neutrophils enables the clear demonstration of the clinical benefit, the role of therapeutic granulocyte transfusions remains controversial. Future directions may include: identifying the patient population who would benefit most from granulocyte transfusions; minimizing the risk of adverse events by identifying the risk factors and the prevention methods; and finding a way to prove the clinical benefit of granulocyte transfusions in therapeutic and prophylactic settings. PMID- 26554891 TI - Sensing and translation of pathogen signals into demand-adapted myelopoiesis. AB - PURPOSE OF REVIEW: During severe systemic infection, steady-state hematopoiesis is switched to demand-adapted myelopoiesis, leading to increased myeloid progenitor proliferation and, depending on the context and type of pathogen, enhanced granulocytic or monocytic differentiation, respectively. We will review the recent advances in understanding direct and indirect mechanisms by which different pathogen signals are detected and subsequently translated into demand adapted myelopoiesis. RECENT FINDINGS: Enhanced myeloid progenitor proliferation and neutrophil differentiation following infection with prototypic Gram-negative bacterium Escherichia coli is mediated by granulocyte colony-stimulating factor, and reactive oxygen species released from endothelial cells and mature myeloid cells, respectively. Furthermore, hematopoietic stem and progenitor cells directly sense pathogen signals via Toll-like receptors and contribute to emergency granulopoiesis via release and subsequent autocrine and paracrine action of myelopoietic cytokines including IL-6. Moreover, emergency monocytopoiesis upon viral infection depends on T cell-derived IFNgamma and release of IL-6 from bone marrow stromal cells. SUMMARY: A complex picture is evolving in which various hematopoietic and nonhematopoietic cell types interact with the hematopoietic system in an intricate manner to shape an appropriate hematopoietic response to specific infectious stimuli. PMID- 26554892 TI - Langerhans cell origin and regulation. AB - PURPOSE OF REVIEW: This article summarizes recent research on the ontogeny of Langerhans cells and regulation of their homeostasis in quiescent and inflamed conditions. RECENT FINDINGS: Langerhans cells originate prenatally and may endure throughout life, independently of bone marrow-derived precursors. Fate-mapping experiments have recently resolved the relative contribution of primitive yolk sac and fetal liver hematopoiesis to the initial formation of Langerhans cells. In postnatal life, local self-renewal restores Langerhans cell numbers following chronic or low-grade inflammatory insults. However, severe inflammation recruits de-novo bone marrow-derived precursors in two waves; a transient population of classical monocytes followed by uncharacterized myeloid precursors that form a stable self-renewing Langerhans cell network as inflammation subsides. Human CD1c+ dendritic cells have Langerhans cell potential in vitro, raising the possibility that dendritic cell progenitors provide the second wave. Langerhans cell development depends upon transforming growth factor beta receptor signaling with distinct pathways active during differentiation and homeostasis. Langerhans cell survival is mediated by multiple pathways including mechanistic target of rapamycin and extracellular signal-regulated kinase signaling, mechanisms that become highly relevant in Langerhans cell neoplasia. SUMMARY: The study of Langerhans cells continues to provide novel and unexpected insights into the origin and regulation of myeloid cell populations. The melding of macrophage and dendritic cell biology, shaped by a unique habitat, is a special feature of Langerhans cells. PMID- 26554894 TI - Filling the void: allogeneic myeloid cells for transplantation. AB - PURPOSE OF REVIEW: The success of allogeneic haematopoietic stem and progenitor cell (HSPC) transplantations remains inconsistent. Umbilical cord blood (UCB) is a promising source of HSPCs for transplantation, but low cell yield hampers its widespread use. Multiple strategies are being developed to manipulate UCB to either increase HSPC content or enhance bone marrow homing upon transfusion. RECENT FINDINGS: Several ex-vivo manipulation protocols have increased engraftment success in recent phase I/II clinical trials. Additionally, by exploiting knowledge of the transcriptome, mature cells were dedifferentiated into induced haematopoietic stem cells capable of self-renewal and reconstitution of haematopoiesis in vivo. SUMMARY: UCB is a more readily available source of allogeneic transplant material compared with bone marrow and mobilized peripheral blood. However, the number of HSPCs in a graft is correlated to the rate and success of engraftment and UCB grafts typically contain 10 times less cells compared with bone marrow or mobilized peripheral blood grafts that contain around 1 * 108 CD34+ cells. Recently, research efforts have focused on increasing UCB engrafting cells in addition to the methods to accelerate engraftment or to provide transient protection and support until engraftment succeeds. PMID- 26554893 TI - Regulation of tissue infiltration by neutrophils: role of integrin alpha3beta1 and other factors. AB - PURPOSE OF REVIEW: Neutrophils have traditionally been viewed in the context of acute infection and inflammation forming the first line of defense against invading pathogens. Neutrophil trafficking to the site of inflammation requires adhesion and transmigration through blood vessels, which is orchestrated by adhesion molecules, such as beta2 and beta1-integrins, chemokines, and cytokines. The review focuses on recent advances in understanding the regulators of neutrophil recruitment during inflammation in both acute and chronic settings. RECENT FINDINGS: Recent findings suggest that besides the established pathways of selectin or chemokine-mediated integrin activation, signaling by distinct Toll like receptors (TLRs) (especially TLR2, TLR4, and TLR5) can activate integrin dependent neutrophil adhesion. Moreover, the integrin alpha3beta1 has been vitally implicated as a new player in neutrophil recruitment and TLR-mediated responses in septic inflammation. Furthermore, several endogenous inhibitory mechanisms of leukocyte recruitment have been identified, including the secreted molecules Del-1, PTX3, and GDF-15, which block distinct steps of the leukocyte adhesion cascade, as well as novel regulatory signaling pathways, involving the protein kinase AKT1 and IFN-lambda2/IL-28A. SUMMARY: The leukocyte adhesion cascade is a tightly regulated process, subjected to both positive and negative regulators. Dysregulation of this process and hence neutrophil recruitment can lead to the development of inflammatory and autoimmune diseases. PMID- 26554895 TI - Frustrated Lewis Pair Chemistry Derived from Bulky Allenyl and Propargyl Phosphanes. AB - The dimesitylpropargylphosphanes mes2 P-CH2 -C=C-R 6 a (R=H), 6 b (R=CH3 ), 6 c (R=SiMe3 ) and the allene mes2 P-C(CH3 )=C=CH2 (8) were reacted with Piers' borane, HB(C6 F5 )2 . Compound 6 a gave mes2 PCH2 CH=CH(B(C6 F5 )2 ] (9 a). In contrast, addition of HB(C6 F5 )2 to 6 b and 6 c gave mixtures of 9 b (R=CH3 ) and 9 c (R=SiMe3 ) with the regioisomers mes2 P-CH2 -C[B(C6 F5 )2 ]=CRH 2 b (R=CH3 ) and 2 c (R=SiMe3 ), respectively. Compounds 2 b,c underwent rapid phosphane/borane (P/B) frustrated Lewis pair (FLP) reactions under mild conditions. Compound 2 c reacted with nitric oxide (NO) to give the persistent FLP NO radical 11. The systems 2 b,c cleaved dihydrogen at room temperature to give the respective phosphonium/hydridoborate products 13 b,c. Compound 13 c transferred the H(+) /H(-) pair to a small series of enamines. Compound 13 c was also a metal-free catalyst (5 mol %) for the hydrogenation of the enamines. The allene 8 reacted with B(C6 F5 )3 to give the zwitterionic phosphonium/borate 17. The -PPh2 -substituted mes2 P-propargyl system 6 d underwent a typical 1,2-P/B addition reaction to the C=C triple bond to form the phosphetium/borate zwitterion 20. Several products were characterized by X-ray diffraction. PMID- 26554896 TI - On-chip automation of cell-free protein synthesis: new opportunities due to a novel reaction mode. AB - Many pharmaceuticals are proteins or their development is based on proteins. Cell free protein synthesis (CFPS) is an innovative alternative to conventional cell based systems which enables the production of proteins with complex and even new characteristics. However, the short lifetime, low protein production and expensive reagent costs are still limitations of CFPS. Novel automated microfluidic systems might allow continuous, controllable and resource conserving CFPS. The presented microfluidic TRITT platform (TRITT for Transcription - RNA Immobilization & Transfer - Translation) addresses the individual biochemical requirements of the transcription and the translation step of CFPS in separate compartments, and combines the reaction steps by quasi-continuous transfer of RNA templates to enable automated CFPS. In detail, specific RNA templates with 5' and 3' hairpin structures for stabilization against nucleases were immobilized during in vitro transcription by newly designed and optimized hybridization oligonucleotides coupled to magnetizable particles. Transcription compatibility and reusability for immobilization of these functionalized particles was successfully proven. mRNA transfer was realized on-chip by magnetic actuated particle transfer, RNA elution and fluid flow to the in vitro translation compartment. The applicability of the microfluidic TRITT platform for the production of the cytotoxic protein Pierisin with simultaneous incorporation of a non-canonical amino acid for fluorescence labeling was demonstrated. The new reaction mode (TRITT mode) is a modified linked mode that fulfills the precondition for an automated modular reactor system. By continual transfer of new mRNA, the novel procedure overcomes problems caused by nuclease digestion and hydrolysis of mRNA during TL in standard CFPS reactions. PMID- 26554897 TI - Spin Coherence and Dephasing of Localized Electrons in Monolayer MoS2. AB - We report a systematic study of coherent spin precession and spin dephasing in electron-doped monolayer MoS2. Using time-resolved Kerr rotation spectroscopy and applied in-plane magnetic fields, a nanosecond time scale Larmor spin precession signal commensurate with g-factor |g0| ? 1.86 is observed in several different MoS2 samples grown by chemical vapor deposition. The dephasing rate of this oscillatory signal increases linearly with magnetic field, suggesting that the coherence arises from a subensemble of localized electron spins having an inhomogeneously broadened distribution of g-factors, g0 + Deltag. In contrast to g0, Deltag is sample-dependent and ranges from 0.042 to 0.115. PMID- 26554898 TI - Solid-State and Solution Structures of Glycinimine-Derived Lithium Enolates. AB - A combination of crystallographic, spectroscopic, and computational studies was applied to study the structures of lithium enolates derived from glycinimines of benzophenone and (+)-camphor. The solvents examined included toluene and toluene containing various concentrations of tetrahydrofuran, N,N,N',N' tetramethylethylenediamine (TMEDA), (R,R)-N,N,N',N'-tetramethylcyclohexanediamine [(R,R)-TMCDA], and (S,S)-N,N,N',N'-tetramethylcyclohexanediamine [(S,S)-TMCDA]. Crystal structures show chelated monomers, symmetric disolvated dimers, S4 symmetric tetramers, and both S6- and D3d-symmetric hexamers. (6)Li NMR spectroscopic studies in conjunction with the method of continuous variations show how these species distribute in solution. Density functional theory computations offer insights into experimentally elusive details. PMID- 26554900 TI - Proteogenomic Discovery of a Small, Novel Protein in Yeast Reveals a Strategy for the Detection of Unannotated Short Open Reading Frames. AB - In recent years, proteomic data have contributed to genome annotation efforts, most notably in humans and mice, and spawned a field termed "proteogenomics". Yeast, in contrast with higher eukaryotes, has a small genome, which has lent itself to simpler ORF prediction. Despite this, continual advances in mass spectrometry suggest that proteomics should be able to improve genome annotation even in this well-characterized species. Here we applied a proteogenomics workflow to yeast to identify novel protein-coding genes. Specific databases were generated, from intergenic regions of the genome, which were then queried with MS/MS data. This suggested the existence of several putative novel ORFs of <100 codons, one of which we chose to validate. Synthetic peptides, RNA-Seq analysis, and evidence of evolutionary conservation allowed for the unequivocal definition of a new protein of 78 amino acids encoded on chromosome X, which we dub YJR107C A. It encodes a new type of domain, which ab initio modeling suggests as predominantly alpha-helical. We show that this gene is nonessential for growth; however, deletion increases sensitivity to osmotic stress. Finally, from the above discovery process, we discuss a generalizable strategy for the identification of short ORFs and small proteins, many of which are likely to be undiscovered. PMID- 26554899 TI - Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells. AB - The field of tissue engineering entered a new era with the development of human pluripotent stem cells (hPSCs), which are capable of unlimited expansion whilst retaining the potential to differentiate into all mature cell populations. However, these cells harbor significant risks, including tumor formation upon transplantation. One way to mitigate this risk is to develop expandable progenitor cell populations with restricted differentiation potential. Here, we used a cellular microarray technology to identify a defined and optimized culture condition that supports the derivation and propagation of a cell population with mesodermal properties. This cell population, referred to as intermediate mesodermal progenitor (IMP) cells, is capable of unlimited expansion, lacks tumor formation potential, and, upon appropriate stimulation, readily acquires properties of a sub-population of kidney cells. Interestingly, IMP cells fail to differentiate into other mesodermally-derived tissues, including blood and heart, suggesting that these cells are restricted to an intermediate mesodermal fate. PMID- 26554901 TI - Intimate partner violence and psychosocial health, a cross-sectional study in a pregnant population. AB - BACKGROUND: The objective of this paper is to explore whether IPV 12 months before and/or during pregnancy is associated with poor psychosocial health. METHODS: From June 2010 to October 2012, a cross-sectional study was conducted in 11 antenatal care clinics in Belgium. Consenting pregnant women were asked to complete a questionnaire on socio-demographics, psychosocial health and violence in a separate room. Overall, 2586 women were invited to participate and we were able to use data from 1894 women (73.2%) for analysis. Ethical clearance was obtained in all participating hospitals. RESULTS: We found a significant correlation between IPV and poor psychosocial health: within the group of women who reported IPV, 53.2% (n = 118) had poor psychosocial health, as compared to 21% (n = 286) in the group of women who did not report IPV (P < 0.001). Lower psychosocial health scores were associated with increased odds of reporting IPV (aOR 1.55; 95% CI 1.39-1.72), with adjustments made for the language in which the questionnaire was filled out, civil/marital status, education and age. In other words, a decrease of 10 points on the psychosocial health scale (total of 140) increased the odds of reporting IPV by 55 %. When accounting for the 6 psychosocial health subscales, the analysis revealed that all subscales (depression, anxiety, self-esteem, mastery, worry and stress) are strongly correlated to reporting IPV. However, when accounting for all subscales simultaneously in a logistic regression model, only depression (aOR 0.87; 95 % CI 0.84-0.91) and stress (aOR 0.85; 95 % CI 0.77-095) remained significantly associated with IPV. The association between overall psychosocial health and IPV remained significant after adjusting for socio-demographic status. CONCLUSION: Our research corroborated that IPV and psychosocial health are strongly associated. Due to the limitations of our study design, we believe that future research is needed to deepen understanding of the multitude of factors involved in the complex interactions between IPV and psychosocial health. PMID- 26554903 TI - The RNA Stem-Loop to G-Quadruplex Equilibrium Controls Mature MicroRNA Production inside the Cell. AB - The biological role of the existence of overlapping structures in RNA is possible yet remains very unexplored. G-Rich tracts of RNA form G-quadruplexes, while GC rich sequences prefer stem-loop structures. The equilibrium between alternate structures within RNA may occur and influence its functionality. We tested the equilibrium between G-quadruplex and stem-loop structure in RNA and its effect on biological processes using pre-miRNA as a model system. Dicer enzyme recognizes canonical stem-loop structures in pre-miRNA to produce mature miRNAs. Deviation from stem-loop leads to deregulated mature miRNA levels, providing readout of the existence of an alternate structure per se G-quadruplex-mediated structural interference in miRNA maturation. In vitro analysis using beacon and Dicer cleavage assays indicated that mature miRNA levels depend on relative amounts of K(+) and Mg(2+) ions, suggesting an ion-dependent structural shift. Further in cellulo studies with and without TmPyP4 (RNA G-quadruplex destabilizer) demonstrated that miRNA biogenesis is modulated by G-quadruplex to stem-loop equilibrium in a subset of pre-miRNAs. Our combined analysis thus provides evidence of the formation of noncanonical G-quadruplexes in competition with canonical stem-loop structure inside the cell and its effect on miRNA maturation in a comprehensive manner. PMID- 26554902 TI - Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system. AB - BACKGROUND: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The objective of the present study was to test a potential role of renal medullary PRR during angiotensin II-induced hypertension. METHODS: A rat AngII infusion model (100 ng/kg/min) combined with renal intramedullary infusion of PRO20, a specific inhibitor of PRR, was builded. And the intravenous PRO20 infusion serve as control. Mean arterial pressure was recorded by radiotelemetry for one week. Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro. RESULTS: Radiotelemetry demonstrated that AngII infusion elevated the mean arteria pressure from 108 +/- 5.8 to 164.7 +/- 6.2 mmHg. Mean arterial pressure decreased to 128.6 +/- 5.8 mmHg (P < 0.05) after intramedullary infusion of PRO20, but was only modestly affected by intravenous PRO20 infusion. Indices of kidney injury, including proteinuria, glomerulosclerosis, and interstitial fibrosis, inflammation, and increased renal medullary and urinary renin activity following angiotensin II infusion were all remarkably attenuated by intramedullary PRO20 infusion. Following one week of angiotensin II infusion, increased PRR immunoreactivity was found in vascular smooth muscle cells. In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20. CONCLUSION: Renal medullary PRR mediates angiotensin II-induced hypertension, likely by amplifying the local renin response. PMID- 26554904 TI - Therapeutic drug monitoring of antimicrobials. AB - As pathology services become more centralized and automated, the measurement of therapeutic antimicrobial drugs concentrations is increasingly performed in clinical biochemistry or 'blood science' laboratories. This review outlines key groups of antimicrobial agents: aminoglycosides, glycopeptides, antifungal agents and antituberculosis agents, their role in managing infectious diseases, and the reasons why serum concentration measurement is important. PMID- 26554905 TI - Pathways towards Precision Medicine in Cancer Management Using Genomic Information. PMID- 26554906 TI - Clonality: A New Marker for Gastric Cancer Survival. PMID- 26554908 TI - Integrate Omics Data and Molecular Dynamics Simulations toward Better Understanding of Human 14-3-3 Interactomes and Better Drugs for Cancer Therapy. AB - The 14-3-3 protein family is among the most extensively studied, yet still largely mysterious protein families in mammals to date. As they are well recognized for their roles in apoptosis, cell cycle regulation, and proliferation in healthy cells, aberrant 14-3-3 expression has unsurprisingly emerged as instrumental in the development of many cancers and in prognosis. Interestingly, while the seven known 14-3-3 isoforms in humans have many similar functions across cell types, evidence of isoform-specific functions and localization has been observed in both healthy and diseased cells. The strikingly high similarity among 14-3-3 isoforms has made it difficult to delineate isoform-specific functions and for isoform-specific targeting. Here, we review our knowledge of 14 3-3 interactome(s) generated by high-throughput techniques, bioinformatics, structural genomics and chemical genomics and point out that integrating the information with molecular dynamics (MD) simulations may bring us new opportunity to the design of isoform-specific inhibitors, which can not only be used as powerful research tools for delineating distinct interactomes of individual 14-3 3 isoforms, but also can serve as potential new anti-cancer drugs that selectively target aberrant 14-3-3 isoform. PMID- 26554907 TI - Oncogenic Signaling Adaptor Proteins. AB - Signal transduction pathways activated by receptor tyrosine kinases (RTK) play a critical role in many aspects of cell function. Adaptor proteins serve an important scaffolding function that facilitates key signaling transduction events downstream of RTKs. Recent work integrating both structural and functional genomic approaches has identified several adaptor proteins as new oncogenes. In this review, we focus on the discovery, structure and function, and therapeutic implication of three of these adaptor oncogenes, CRKL, GAB2, and FRS2. Each of the three genes is recurrently amplified in lung adenocarcinoma or ovarian cancer, and is essential to cancer cell lines that harbor such amplification. Overexpression of each gene is able to transform immortalized human cell lines in in vitro or in vivo models. These observations identify adaptor protein as a distinct class of oncogenes and potential therapeutic targets. PMID- 26554909 TI - Genetic Polymorphism, Telomere Biology and Non-Small Lung Cancer Risk. AB - Recent genome-wide association studies (GWAS) have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms (SNPs), especially rs2736100 located in the telomerase reverse transcriptase (TERT) gene show unique and significant association with non-small cell lung cancer (NSCLC) in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma. Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental (e.g., less-smoking) and physiological factors (gender and age) that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor (EGFR) mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity. By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC. PMID- 26554910 TI - MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) is considered to be the most lethal and aggressive malignancy with high mortality and poor prognosis. Their responses to current multimodal therapeutic regimens are limited. It is urgently needed to identify the molecular mechanism underlying pancreatic oncogenesis. Twelve core signaling cascades have been established critical in PDAC tumorigenesis by governing a wide variety of cellular processes. MicroRNAs (miRNAs) are aberrantly expressed in different types of tumors and play pivotal roles as post transcriptional regulators of gene expression. Here, we will describe how miRNAs regulate different signaling pathways that contribute to pancreatic oncogenesis and progression. PMID- 26554911 TI - Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing. AB - Few effective therapies have been developed for the treatment of lung squamous cell carcinoma (SQCC), in part due to a lack of understanding regarding the mechanisms underlying the initiation and development of this disease. Whole transcriptome sequencing not only provides insight into the expression of all transcribed genes, but offers an efficient approach for identifying genetic variations, including gene fusions, mutations and alternative splicing. In this study, we performed whole transcriptome sequencing of 10 patients with stage IIIA lung SQCC, and discovered a large number of single nucleotide variants (SNVs; mean of 12.2 SNVs/Mb), with C>T/G>A and A>G/T>C transitions being the most frequently observed. Additionally, a total of 132 gene fusions were identified based upon TopHat alignments, 70.5% (93/132) of which occurred as a result of intra-chromosomal rearrangements. Based on the number of supporting reads for each fusion, we further validated 20 of the 26 top gene fusions by RT-PCR and Sanger sequencing. Taken together, these data provide an in-depth view of transcriptional alterations in lung SQCC patients, and may be useful for identification of new therapeutic targets. PMID- 26554912 TI - Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development. AB - Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C (XPC) are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog (Kras) or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, Kras(LA1), as a driver for lung cancer development in mice, we showed for the first time that mice with Kras(LA1) and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured cells, we demonstrated that induced expression of oncogenic KRAS(G12V) led to increased levels of reactive oxygen species (ROS) as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS. PMID- 26554913 TI - Increased BST2 expression during simian immunodeficiency virus infection is not a determinant of disease progression in rhesus monkeys. AB - BACKGROUND: Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load. RESULTS: Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course. CONCLUSION: The detected relationship between BST2 expression and viral load as well as with MX1 indicate a common regulation by the interferon response and suggest rather limited influence of BST2 in vivo on the disease outcome. PMID- 26554914 TI - A phylogeny of Cichlidogyrus spp. (Monogenea, Dactylogyridea) clarifies a host switch between fish families and reveals an adaptive component to attachment organ morphology of this parasite genus. AB - BACKGROUND: Parasite switches to new host species are of fundamental scientific interest and may be considered an important speciation mechanism. For numerous monogenean fish parasites, infecting different hosts is associated with morphological adaptations, in particular of the attachment organ (haptor). However, haptoral morphology in Cichlidogyrus spp. (Monogenea, Dactylogyridea), parasites of African cichlids, has been mainly linked to phylogenetic rather than to host constraints. Here we determined the position of Cichlidogyrus amieti, a parasite of species of Aphyosemion (Cyprinodontiformes, Nothobranchiidae) in the phylogeny of its congeners in order to infer its origin and assess the morphological changes associated with host-switching events. METHODS: The DNA of specimens of C. amieti isolated from Aphyosemion cameronense in Cameroon was sequenced and analyzed together with that of Cichlidogyrus spp. from cichlid hosts. In order to highlight the influence of the lateral transfer of C. amieti on the haptoral sclerotised parts we performed a Principal Component Analysis (PCA) to compare the attachment organ structure of C. amieti to that of congeners infecting cichlids. RESULTS: Cichlidogyrus amieti was found to be nested within a strongly supported clade of species described from Hemichromis spp. (i.e. C. longicirrus and C. dracolemma). This clade is located at a derived position of the tree, suggesting that C. amieti transferred from cichlids to Cyprinodontiformes and not inversely. The morphological similarity between features of their copulatory organs suggested that C. amieti shares a recent ancestor with C. dracolemma. It also indicates that in this case, these organs do not seem subjected to strong divergent selection pressure. On the other hand, there are substantial differences in haptoral morphology between C. amieti and all of its closely related congeners described from Hemichromis spp.. CONCLUSIONS: Our study provides new evidence supporting the hypothesis of the adaptive nature of haptor morphology. It demonstrates this adaptive component for the first time within Cichlidogyrus, the attachment organs of which were usually considered to be mainly phylogenetically constrained. PMID- 26554915 TI - Autoimmunity in picornavirus infections. AB - Enteroviruses are small, non-enveloped, positive-sense single-strand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler's virus infection is the first demonstration of this autoimmune mechanism. PMID- 26554917 TI - Transferability of the coarse-grained potentials for trans-1,4-polybutadiene. AB - In this paper, we evaluate the transferability of the coarse-grained (CG) force field (FF) of trans-1,4-polybutadiene which was built via a combined structure based and thermodynamic quantity-based CG method at 413 K and 1 atm by systematically examining CG simulated structural and thermodynamic properties against the underlying atomistic simulation results at different temperatures. Interestingly, the derived CG force field exhibits good "state-point transferability" to some extent. For example, when applying this CG FF to the nearby state point (e.g., amorphous phase at 500 K), the resulting local conformation statistics, chain size, and local packing properties as well as density values for the CG models closely match the atomistic simulated data. When further applying this CG force field to the crystalline state at 300 K, the structural and thermodynamic properties of the crystalline phase formed for these CG and atomistic MD simulations still match within a certain level of accuracy. Furthermore, the CG torsion potential has a dual effect: for the amorphous state, the presence of an intramolecular energy barrier against rotation improves the capability of CG models to more precisely reproduce the structural properties, while in the crystalline state this CG torsion barrier suppresses the formation of the more fully stretched chain with a higher trans content. As a result, in the crystalline phase the CG model chains without torsion potentials possess a more stretched chain conformation, pack more efficiently, and have a higher crystallinity degree than its counterpart with CG torsion potentials as well as its underlying atomistic model. However, the dual effect of CG torsion potentials does not mean that we have to use different dihedral parameters to describe different state points. Both CG FFs, one with and another without torsion potentials, are able to represent the melt and the crystalline states. Overall, the phase and its structural consistency between the CG and atomistic models over other state points (e.g., crystalline phase) for which CG FFs were not explicitly parameterized very encouraging such that the combined structure-based and thermodynamic quantity-based CG method can be used to derive an optimized CG FF for multi-scale simulation of polymer systems under different thermodynamic conditions. PMID- 26554916 TI - Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders. AB - BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value >= 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care. PMID- 26554918 TI - Metamorphopsia: An Overlooked Visual Symptom. AB - Metamorphopsia is a common symptom in different macular disorders. Micropsia and macropsia are special types of metamorphopsia. Recent theories suggest that both retinal and cortical mechanisms are involved in the development and changes of metamorphopsia. Different functional tests have been proposed for the evaluation of metamorphopsia: from the Amsler grid to the hand-held mobile devices for home monitoring. This review addresses some new insights into the pathophysiology of metamorphopsia and different available tests for the evaluation of this symptom in most common macular disorders. The importance of quantification of metamorphopsia in macular diseases is confirmed by the most recent therapeutic approaches. PMID- 26554919 TI - Comparative Prevalence of Immune Evasion Complex Genes Associated with beta Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact. AB - Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC) genes carried by beta-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with beta-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the beta-hemolysin gene was intact in these strains, indicating the bacteriophage's absence. In contrast, the prevalence of the beta-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of beta-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates may harbor a reduced capacity to cause severe disease in immunocompetent humans. PMID- 26554920 TI - The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer. AB - BACKGROUND: Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear. METHODS: We estimated the familial concordance and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death. RESULTS: From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose co-twins had breast cancer was 28% among monozygotic and 20% among dizygotic twins. The heritability of liability to breast cancer was 31% [95% confidence interval (CI), 10%-51%] and the common environmental component was 16% (95% CI, 10%-32%). For premenopausal breast cancer these estimates were 27% and 12%, respectively, and for postmenopausal breast cancer 22% and 16%, respectively. The relative contributions of genetic and environmental factors were constant between ages 50 and 96. Our results are compatible with the Peto-Mack hypothesis. CONCLUSION: Our findings indicate that familial factors explain almost half of the variation in liability to develop breast cancer, and results were similar for pre- and postmenopausal breast cancer IMPACT: We estimate heritability of breast cancer, taking until now ignored sources of bias into account. PMID- 26554921 TI - Detection and Genetic Characteristics of H9N2 Avian Influenza Viruses from Live Poultry Markets in Hunan Province, China. AB - H9N2 avian influenza viruses (AIVs) are highly prevalent and of low pathogenicity in domestic poultry. These viruses show a high genetic compatibility with other subtypes of AIVs and have been involved in the genesis of H5N1, H7N9 and H10N8 viruses causing severe infection in humans. The first case of human infection with H9N2 viruses in Hunan province of China have been confirmed in November 2013 and identified that H9N2 viruses from live poultry markets (LPMs) near the patient's house could be the source of infection. However, the prevalence, distribution and genetic characteristics of H9N2 viruses in LPMs all over the province are not clear. We collected and tested 3943 environmental samples from 380 LPMs covering all 122 counties/districts of Hunan province from February to April, 2014. A total of 618 (15.7%) samples were H9 subtype positive and 200 (52.6%) markets in 98 (80.3%) counties/districts were contaminated with H9 subtype AIVs. We sequenced the entire coding sequences of the genomes of eleven H9N2 isolates from environmental samples. Phylogenetic analysis showed that the gene sequences of the H9N2 AIVs exhibited high homology (94.3%-100%). All eleven viruses were in a same branch in the phylogenetic trees and belonged to a same genotype. No gene reassortment had been found. Molecular analysis demonstrated that all the viruses had typical molecular characteristics of contemporary avian H9N2 influenza viruses. Continued surveillance of AIVs in LPMs is warranted for identification of further viral evolution and novel reassortants with pandemic potential. PMID- 26554922 TI - Dispersal of Engineered Male Aedes aegypti Mosquitoes. AB - BACKGROUND: Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in a sterile insect control programme. To improve our understanding of the dispersal ecology of mosquitoes and to inform appropriate release strategies of 'genetically sterile' male Aedes aegypti detailed knowledge of the dispersal ability of the released insects is needed. METHODOLOGY/PRINCIPAL FINDINGS: The dispersal ability of released 'genetically sterile' male Aedes aegypti at a field site in Brazil has been estimated. Dispersal kernels embedded within a generalized linear model framework were used to analyse data collected from three large scale mark release recapture studies. The methodology has been applied to previously published dispersal data to compare the dispersal ability of 'genetically sterile' male Aedes aegypti in contrasting environments. We parameterised dispersal kernels and estimated the mean distance travelled for insects in Brazil: 52.8 m (95% CI: 49.9 m, 56.8 m) and Malaysia: 58.0 m (95% CI: 51.1 m, 71.0 m). CONCLUSIONS/SIGNIFICANCE: Our results provide specific, detailed estimates of the dispersal characteristics of released 'genetically sterile' male Aedes aegypti in the field. The comparative analysis indicates that despite differing environments and recapture rates, key features of the insects' dispersal kernels are conserved across the two studies. The results can be used to inform both risk assessments and release programmes using 'genetically sterile' male Aedes aegypti. PMID- 26554923 TI - Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia. AB - BACKGROUND: Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. METHODS: We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study tau2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. RESULTS: Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. CONCLUSIONS: Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals. PMID- 26554924 TI - Macroalgal Composition Determines the Structure of Benthic Assemblages Colonizing Fragmented Habitats. AB - Understanding the consequences of fragmentation of coastal habitats is an important topic of discussion in marine ecology. Research on the effects of fragmentation has revealed complex and context-dependent biotic responses, which prevent generalizations across different habitats or study organisms. The effects of fragmentation in marine environments have been rarely investigated across heterogeneous habitats, since most studies have focused on a single type of habitat or patch. In this study, we assessed the effects of different levels of fragmentation (i.e. decreasing size of patches without overall habitat loss). We measured these effects using assemblages of macro-invertebrates colonizing representative morphological groups of intertidal macroalgae (e.g. encrusting, turf and canopy-forming algae). For this purpose, we constructed artificial assemblages with different combinations of morphological groups and increasing levels of fragmentation by manipulating the amount of bare rock or the spatial arrangement of different species in mixed assemblages. In general, our results showed that 1) fragmentation did not significantly affect the assemblages of macroinvertebrates; 2) at greater levels of fragmentation, there were greater numbers of species in mixed algal assemblages, suggesting that higher habitat complexity promotes species colonization. Our results suggest that predicting the consequences of fragmentation in heterogeneous habitats is dependent on the type and diversity of morphological groups making up those habitats. PMID- 26554925 TI - Respiratory protection for firefighters--Evaluation of CBRN canisters for use during overhaul II: In mask analyte sampling with integrated dynamic breathing machine. AB - According to the National Fire Protection Association there were 487,500 structural fires in the U.S. in 2013. After visible flames are extinguished firefighters begin the overhaul stage where remaining hot spots are identified and further extinguished. During overhaul, a significant amount of potentially hazardous chemicals can remain in the ambient environment. Previous research suggests that the use of air purifying respirators fitted with chemical, biological, radiological, and nuclear (CBRN) canisters may reduce occupational exposure. This study used large scale burns of representative structural materials to perform side-by-side, filtering, and service-life evaluations of commercially available CBRN filters using two head forms fitted with full-face respirators and a dynamic breathing machine. Three types of CBRN canisters and one non-CBRN cartridge were challenged in repetitive post-fire environments. Tests were conducted with two different breathing volumes and rates for two sampling durations (0-15 min and 0-60 min). Fifty-five different chemicals were selected for evaluation and results indicate that 10 of the 55 chemicals were present in the post-fire overhaul ambient environment. Acetaldehyde and formaldehyde were found to be the only two chemicals detected post filter but were effectively filtered to below ACGIH TLVs. Counter to our prior published work using continuous flow filter evaluation, this study indicates that, regardless of brand, CBRN filters were effective at reducing concentrations of post-fire ambient chemicals to below occupational exposure limits. However, caution should be applied when using CBRN filters as the ambient formaldehyde level in the current study was 8.9 times lower than during the previous work. PMID- 26554927 TI - Cerium oxide nanoparticles induce oxidative stress in the sediment-dwelling amphipod Corophium volutator. AB - Cerium oxide nanoparticles (CeO2 NPs) exhibit fast valence exchange between Ce(IV) and Ce(III) associated with oxygen storage and both pro and antioxidant activities have been reported in laboratory models. The reactivity of CeO2 NPs once they are released into the aquatic environment is virtually unknown, but this is important to determine for assessing their environmental risk. Here, we show that amphipods (Corophium volutator) grown in marine sediments containing CeO2 NPs showed a significant increase in oxidative damage compared to those grown in sediments without NPs and those containing large-sized (bulk) CeO2 particles. There was no exposure effect on survival, but significant increases in single-strand DNA breaks, lipid peroxidation and superoxide dismutase activity were observed after a 10-day exposure to 12.5 mg L(-1) CeO2. Characterisation of the CeO2 NPs dispersed in deionised or saline exposure waters revealed that more radicals were produced by CeO2 NPs compared with bulk CeO2. Electron energy loss spectroscopy (EELS) analysis revealed that both CeO2 NPs were predominantly Ce(III) in saline waters compared to deionised waters where they were predominantly Ce(IV). In both types of medium, the bulk CeO2 consisted mainly of Ce(IV). These results support a model whereby redox cycling of CeO2 NPs between Ce(III) and Ce(IV) is enhanced in saline waters, leading to sublethal oxidative damage to tissues in our test organism. PMID- 26554926 TI - Ran Involved in the Development and Reproduction Is a Potential Target for RNA Interference-Based Pest Management in Nilaparvata lugens. AB - Ran (RanGTPase) in insects participates in the 20-hydroxyecdysone signal transduction pathway in which downstream genes, FTZ-F1, Kruppel-homolog 1 (Kr-h1) and vitellogenin, are involved. A putative Ran gene (NlRan) was cloned from Nilaparvata lugens, a destructive phloem-feeding pest of rice. NlRan has the typical Ran primary structure features that are conserved in insects. NlRan showed higher mRNA abundance immediately after molting and peaked in newly emerged female adults. Among the examined tissues ovary had the highest transcript level, followed by fat body, midgut and integument, and legs. Three days after dsNlRan injection the NlRan mRNA abundance in the third-, fourth-, and fifth-instar nymphs was decreased by 94.3%, 98.4% and 97.0%, respectively. NlFTZ F1 expression levels in treated third- and fourth-instar nymphs were reduced by 89.3% and 23.8%, respectively. In contrast, NlKr-h1 mRNA levels were up-regulated by 67.5 and 1.5 folds, respectively. NlRan knockdown significantly decreased the body weights, delayed development, and killed >85% of the nymphs at day seven. Two apparent phenotypic defects were observed: (1) Extended body form, and failed to molt; (2) The cuticle at the notum was split open but cannot completely shed off. The newly emerged female adults from dsNlRan injected fifth-instar nymphs showed lower levels of NlRan and vitellogenin, lower weight gain and honeydew excretion comparing with the blank control, and no offspring. Those results suggest that NlRan encodes a functional protein that was involved in development and reproduction. The study established proof of concept that NlRan could serve as a target for dsRNA-based pesticides for N. lugens control. PMID- 26554928 TI - Critical Parameters of the In Vitro Method of Vascular Smooth Muscle Cell Calcification. AB - BACKGROUND: Vascular calcification (VC) is primarily studied using cultures of vascular smooth muscle cells. However, the use of very different protocols and extreme conditions can provide findings unrelated to VC. In this work we aimed to determine the critical experimental parameters that affect calcification in vitro and to determine the relevance to calcification in vivo. EXPERIMENTAL PROCEDURES AND RESULTS: Rat VSMC calcification in vitro was studied using different concentrations of fetal calf serum, calcium, and phosphate, in different types of culture media, and using various volumes and rates of change. The bicarbonate content of the media critically affected pH and resulted in supersaturation, depending on the concentration of Ca2+ and Pi. Such supersaturation is a consequence of the high dependence of bicarbonate buffers on CO2 vapor pressure and bicarbonate concentration at pHs above 7.40. Such buffer systems cause considerable pH variations as a result of minor experimental changes. The variations are more critical for DMEM and are negligible when the bicarbonate concentration is reduced to 1/4. Particle nucleation and growth were observed by dynamic light scattering and electron microscopy. Using 2mM Pi, particles of ~200nm were observed at 24 hours in MEM and at 1 hour in DMEM. These nuclei grew over time, were deposited in the cells, and caused osteogene expression or cell death, depending on the precipitation rate. TEM observations showed that the initial precipitate was amorphous calcium phosphate (ACP), which converts into hydroxyapatite over time. In blood, the scenario is different, because supersaturation is avoided by a tightly controlled pH of 7.4, which prevents the formation of PO43--containing ACP. CONCLUSIONS: The precipitation of ACP in vitro is unrelated to VC in vivo. The model needs to be refined through controlled pH and the use of additional procalcifying agents other than Pi in order to reproduce calcium phosphate deposition in vivo. PMID- 26554930 TI - The Performance of the Four Anaerobic Blood Culture Bottles BacT/ALERT-FN, -FN Plus, BACTEC-Plus and -Lytic in Detection of Anaerobic Bacteria and Identification by Direct MALDI-TOF MS. AB - Detection and identification of anaerobic bacteria in blood cultures (BC) is a well-recognized challenge in clinical microbiology. We studied 100 clinical anaerobic BC isolates to evaluate the performance of BacT/ALERT-FN, -FN Plus (BioMerieux), BACTEC-Plus and -Lytic (Becton Dickinson BioSciences) BC bottles in detection and time to detection (TTD) of anaerobic bacteria. BACTEC Lytic had higher detection rate (94/100, 94%) than BacT/ALERT FN Plus (80/100, 80%) (p<0.01) in the studied material. There was no significant difference in detection of anaerobic bacteria among the remaining bottle types. The 67 anaerobic bacteria that signalled positive in all four bottle types were analyzed to compare the time to detection (TTD) and isolates were directly identified by MALDI-TOF MS. There was a significant difference in TTD among the four bottle types (p<0.0001). The shortest median TTD was 18 h in BACTEC Lytic followed by BacT/ALERT FN (23.5 h), BACTEC Plus (27 h) and finally BacT/ALERT FN Plus (38 h) bottles. In contrast, MALDI-TOF MS performed similarly in all bottle types with accurate identification in 51/67 (76%) BacT/ALERT FN, 51/67 (76%) BacT/ALERT FN Plus, 53/67 (79%) BACTEC Plus and 50/67 (75%) BACTEC Lytic bottles. In conclusion, BACTEC Lytic bottles have significantly better detection rates and shorter TTD compared to the three other bottle types. The anaerobic BC bottles are equally suitable for direct MALDI-TOF MS for rapid and reliable identification of common anaerobic bacteria. Further clinical studies are warranted to investigate the performance of anaerobic BC bottles in detection of anaerobic bacteria and identification by direct MALDI-TOF MS. PMID- 26554929 TI - Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT1A and 5-HT7 Antagonists in Animal Models. AB - The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2 methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6 methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydrochloride (HBK 15) in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM) in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic alpha1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14-FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg) and (HBK-15-FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg). We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg) and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg) possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds. PMID- 26554931 TI - Role of extracellular vesicles in autoimmune diseases. AB - Extracellular vesicles (EVs) consist of exosomes released upon fusion of multivesicular bodies with the cell plasma membrane and microparticles shed directly from the cell membrane of many cell types. EVs can mediate cell-cell communication and are involved in many processes including inflammation, immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. Accumulating evidence reveals that EVs act in the establishment, maintenance and modulation of autoimmune processes among several others involved in cancer and cardiovascular complications. EVs could also present biomedical applications, as disease biomarkers and therapeutic targets or agents for drug delivery. PMID- 26554932 TI - Impact of a multidisciplinary approach in enteropathic spondyloarthritis patients. AB - Spondyloarthritis (SpA) and inflammatory bowel disease (IBD) are chronic autoinflammatory diseases that partially share the genetic predisposition and the unchecked inflammatory response linking the gut to the joints. The coexistence of both conditions in patients and the increased cross-risk ratios between SpA and IBD strongly suggest a shared pathophysiology. The prevalence of Enteropathic related Spondyloarthritis (ESpA) in IBD patients shows a wide variation and may be underestimated. It is well accepted that the management of joint pain requires rheumatological expertise in conjunction with gastroenterologist assessment. In this view, we aimed at assessing, in a prospective study performed in a combined Gastro-Intestinal and Rheumatologic "GI-Rhe" clinic: (1) the prevalence of ESpA and other rheumatologic diseases in IBD patients with joint pain; (2) the features of the ESpA population; and (3) the diagnostic delay and the potential impact of the combined assessment. From November 2012 to December 2014, IBD patients with joint pain referring to a dedicated rheumatologist by the IBD dedicated gastroenterologist were enrolled. Clinical and biochemical evaluations, joint involvement and disease activity assessment, diagnostic delay, and treatment were recorded. IBD patients (n=269) with joint pain were jointly assessed in the "GI-Rhe" Unit. A diagnosis of ESpA was made in 50.5% of IBD patients with joint pain. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. ESpA patients had a higher prevalence of other autoimmune extra-intestinal manifestations and received more anti-TNF treatment compared with IBD patients. A mean diagnostic delay of 5.2 years was revealed in ESpA patients. Patients with joint disease onset in the 2002-2012 decade had reduced diagnostic delay compared with those with onset in the 1980-1990 and 1991-2001 decades. Diagnostic delay was further reduced for patients with joint onset in the last two years in conjunction with the establishment of the GI-Rhe clinic. Multidisciplinary approach improved management of rheumatic disorders in IBD patients allowing a more comprehensive care. PMID- 26554933 TI - Autoimmune progesterone dermatitis: Update and insights. AB - Autoimmune progesterone dermatitis (APD) is rare autoimmune hypersensitivity reaction to the fluctuations of endogenous progesterone during a woman's menstrual cycle. It has a wide spectrum of clinical presentations including urticaria, eczema and vesiculobullous eruptions. The disease course depends on treatment modality. The pathogenic mechanisms of APD remain to be elucidated. OBJECTIVE: We aim to review the literature on APD and evaluate the different theories of pathogenesis and treatments for this condition. METHODS: A review of the English literature on APD was performed using PubMed, EMBASE and MEDLINE. RESULTS: 89 patients are included in this review. Initial symptom development in association with the menstrual cycle was reported in 65 (73%) patients. In some patients, it occurred shortly after hormone therapy (8.9%) or in relation to a pregnancy (14.6%). Associated factors were not defined in three patients (3.4%). Nearly 45% had a history of exposure to exogenous progesterone. Diagnosis of APD was usually confirmed with an intradermal progesterone sensitivity test. The goal of treatment was to suppress progesterone secretion through anovulation. Some cases were controlled with oral contraceptives or conjugated estrogen, while some patients had complete resolution post-hysterectomy. CONCLUSION: The wide spectrum of clinical presentations, histology, and response to therapy would suggest that there are multiple subsets in APD. The increase in the levels of progesterone may also influence the clinical profile and the corresponding immunological response. Further research on the pathogenesis of APD is required to provide a satisfactory treatment modality. PMID- 26554934 TI - TLX: An elusive receptor. AB - TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. PMID- 26554935 TI - Vitamin D levels and breast cancer characteristics: Findings in patients from Saudi Arabia. AB - Inverse relationship between vitamin D status and risk of breast cancer has been previously reported in the literature. We conducted this study to determine the association between vitamin D levels and breast cancer characteristics in patients from Saudi Arabia. Newly diagnosed breast cancer patients (N=406) were recruited. Serum levels of 25-hydroxyvitamin D [25 (OH) D] were measured at baseline. A significantly higher percentage of patients with triple negative status (18%) had 25 (OH) D levels <=25nmol/L, compared to only 8% with 25 (OH) D levels >25nmol/L (p=0.009). Patients with 25 (OH) D levels <=25nmol/L were 2.54 times more likely to present with triple negative status compared to those with 25 (OH) D levels >25nmol/L (p=0.02). Our findings suggest an association between low 25 (OH) D levels and increased risk of triple negative breast cancer. PMID- 26554936 TI - Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates. AB - BACKGROUND: Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D-1,25(OH)2D takes place at 40 ng/mL in pregnant women. OBJECTIVE: Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community. METHODS: Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of <=20 ng/mL, >20 to <40 ng/mL, and >=40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth. RESULTS: Women with serum 25(OH)D concentrations >=40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations <=20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ~40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations >=40 ng/mL (n=92) compared to those with 25(OH)D concentrations <=20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations >=40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04). CONCLUSIONS: In this post-hoc analysis, achieving a 25(OH)D serum concentration >=40 ng/mL significantly decreased the risk of preterm birth compared to <=20 ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20 ng/mL; reaching 40 ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone. PMID- 26554937 TI - Triptolide Inhibited Cytotoxicity of Differentiated PC12 Cells Induced by Amyloid Beta25-35 via the Autophagy Pathway. AB - Evidence shows that an abnormal deposition of amyloid beta-peptide25-35 (Abeta25 35) was the primary cause of the pathogenesis of Alzheimer's disease (AD). And the elimination of Abeta25-35 is considered an important target for the treatment of AD. Triptolide (TP), isolated from Tripterygium wilfordii Hook.f. (TWHF), has been shown to possess a broad spectrum of biological profiles, including neurotrophic and neuroprotective effects. In our study investigating the effect and potential mechanism of triptolide on cytotoxicity of differentiated rat pheochromocytoma cell line (the PC12 cell line is often used as a neuronal developmental model) induced by Amyloid-Beta25-35 (Abeta25-35), we used 3-(4, 5 dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) assay, flow cytometry, Western blot, and acridine orange staining to detect whether triptolide could inhibit Abeta25-35-induced cell apoptosis. We focused on the potential role of the autophagy pathway in Abeta25-35-treated differentiated PC12 cells. Our experiments show that cell viability is significantly decreased, and the apoptosis increased in Abeta25-35-treated differentiated PC12 cells. Meanwhile, Abeta25-35 treatment increased the expression of microtubule associated protein light chain 3 II (LC3 II), which indicates an activation of autophagy. However, triptolide could protect differentiated PC12 cells against Abeta25-35-induced cytotoxicity and attenuate Abeta25-35-induced differentiated PC12 cell apoptosis. Triptolide could also suppress the level of autophagy. In order to assess the effect of autophagy on the protective effects of triptolide in differentiated PC12 cells treated with Abeta25-35, we used 3-Methyladenine (3 MA, an autophagy inhibitor) and rapamycin (an autophagy activator). MTT assay showed that 3-MA elevated cell viability compared with the Abeta25-35-treated group and rapamycin inhibits the protection of triptolide. These results suggest that triptolide will repair the neurological damage in AD caused by deposition of Abeta25-35 via the autophagy pathway, all of which may provide an exciting view of the potential application of triptolide or TWHF as a future research for AD. PMID- 26554938 TI - Inhibition of TGFbeta cell signaling for limbal explant culture in serumless, defined xeno-free conditions. AB - Outgrowths of limbal epithelium by explant culture are used to treat limbal stem cell deficiency (LSCD). The explant culture medium is always complemented with serum, a complex solution which includes TGFbeta. Since TGFbeta is a cytostatic effector for epithelial proliferation we examined its effect on these cultures. Limbal biopsies were set on explant culture in DMEM/F12 with 5 ng/ml EGF and cholera toxin (ChT), ITS, and 5% FBS, henceforth SHEM or a) SHEMSB=SHEM plus SB431542 an inhibitor of TGFbeta signaling; b) sfSHEM = SHEM with FBS replaced by 0.05% Albumax II; and c) sfSHEMSB and sfSHEMA83 = sfSHEM plus, respectively, SB431542 or A-83-01, another TGFbeta inhibitor. After the initial outgrowths reached 3 cm in diameter, the limbal biopsies were serially transferred up to six times onto new inserts. Biopsy explant outgrowths were trypsinized and cell yield, morphology and stem-cell related JC-1 exclusion (IOVS, 52:4330) were determined by flow cytometry. Cells we plated at low density seeding to compare relative clonal proliferative activity. The expression of three proteins whose levels are associated with growth and differentiation states, Krt3, connexin 43 and p63 were determined by immunohistology and/or Western blot. Cell yield in rabbit, relative to SHEM (in %) were, SHEMSB, 104 +/- 13 (p > 0.95); sfSHEM: 5 +/ 3; and sfSHEMSB, 94 +/- 18 (p > 0.95). Cell size and morphology, JC1 dye exclusion, Krt3, p63 and connexin 43 content, proliferation efficiency and the preservation of extended proliferative potential of the serially cultured biopsies were similar for SHEM, SHEMSB and sfSHEMSB. The only differences observed where reduced expression of Krt3 and increased preservation of p63 in the FBS-free medium. Removal of EGF from sfSHEMSB reduced yield by 92 +/- 6% (p < 0.05). Removal of Albumax and ChT to establish a xeno-free medium caused a small, non-statistical decrease in growth rates. Equivalent results were observed in a preliminary experiment in human. These results suggest that in the absence serum endogenously generated TGFbeta act as an autocrine cytostatic agent and that TGFbeta inhibitors allow explant culture in xeno-free, chemically defined medium. Furthermore, the pro-growth effect of serum in limbal explant cultures may result exclusively from neutralization of the TGFbeta cytostatic effect. PMID- 26554939 TI - The effects of the apoE4 genotype on the developing mouse retina. AB - Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. The retina, which is as an extension of the central nervous system (CNS), is a particularly suitable model for studying developmental and functional aspects of the neuronal and vascular systems. This study investigates the apoE4-dependent developmental effects on the retinal vasculature and neuronal systems and on the levels of apoE and the vascular endothelial growth factor (VEGF) in the retina. This was performed utilizing retinas of 4, 7, 12, and of 120-day-old human-apoE4-targeted replacement mice and of corresponding mice that express the AD benign isoform, apoE3. The results obtained revealed retinal vascular pathology in the apoE4 mice, which started on the early post-natal days. This includes transient increase in vascular branching, and vascular buds which are round vascular elements representing sprouting or retracting vessels. These effects peaked and ended during the neonatal period. Examination of the synaptic system utilizing the pre-synaptic marker synaptophysin revealed a significant decrease of retinal synaptic density in the apoE4 mice, which was detectable by post-natal day 12 (P12). These morphological changes are associated with neonatal age-dependent elevation in the apoE levels in both apoE3 and apoE4 retinas which is more profound in the apoE4 mice and a corresponding increase in VEGF levels, which is less profound in the apoE4 mice. Additionally, we observed lower levels of retinal VEGF in the apoE4 mice compared to the apoE3 mice retinas on P12. These results show that apoE4 has a transient vascular effect during retinal development that ends in the neonatal period, which is accompanied by a synaptic effect that begins at the end of the neonatal period. These findings show that the apoE4 genotype can have distinct developmental effects on both the retinal vasculature and on neurons and suggest that the vascular effects of apoE4 may be related to reduced levels of VEGF. PMID- 26554940 TI - Assessing the performance of novel software Strain Solution on automated discrimination of Escherichia coli serotypes and their mixtures using matrix assisted laser desorption ionization-time of flight mass spectrometry. AB - O157, O26, and O111 are the most important O serogroups of enterohemorrhagic Escherichia coli worldwide. Recently we reported a strategy for discriminating these serotypes from the others using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) based on the S10-spc-alpha operon gene-encoded ribosomal protein mass spectrum (S10-GERMS) method. To realize the fully automated identification of microorganisms at species- or serotype-level with the concept of S10-GERMS method, novel software named Strain Solution for MALDI-TOF MS was developed. In this study, the Strain Solution was evaluated with a total of 45 E. coli isolates including O26, O91, O103, O111, O115, O121, O128, O145, O157, O159, and untyped serotypes. The Strain Solution could accurately discriminate 92% (11/12) of O157 strains, 100% (13/13) of O26 and O111 strains from the others with three biomarkers in an automated manner. In addition, this software could identify 2 different E. coli strains (K-12 as a non-O157 representative and O157) in mixed samples. The results suggest that Strain Solution will be useful for species- or serotype-level classification of microorganisms in the fields of food safety and diagnostics. PMID- 26554941 TI - Selection of fluorescent DNA dyes for real-time LAMP with portable and simple optics. AB - Loop-mediated isothermal amplification (LAMP) is increasingly used for point-of care nucleic acid based diagnostics. LAMP can be monitored in real-time by measuring the increase in fluorescence of DNA binding dyes. However, there is little information comparing the effect of various fluorescent dyes on signal to noise ratio (SNR) or threshold time (Tt). This information is critical for implementation with field deployable diagnostic tools that require small, low power consumption, robust, and inexpensive optical components with reagent saving low volume reactions. In this study, SNR and Tt during real-time LAMP was evaluated with eleven fluorescent dyes. Of all dyes tested, SYTO-82, SYTO-84, and SYTOX Orange resulted in the shortest Tt, and SYTO-81 had the widest range of working concentrations. The optimized protocol detected 10 genome copies of Mycobacterium tuberculosis in less than 10 min, 10 copies of Giardia intestinalis in ~20 min, and 10 copies of Staphylococcus aureus or Salmonella enterica in less than 15 min. Results demonstrate that reaction efficiency depends on both dye type and concentration and the selected polymerase. The optimized protocol was evaluated in the Gene-ZTM device, a hand-held battery operated platform characterized via simple and low cost optics, and a multiple assay microfluidic chip with micron volume reaction wells. Compared to the more conventional intercalating dye (SYBR Green), reliable amplification was only observed in the Gene-ZTM when using higher concentrations of SYTO-81. PMID- 26554942 TI - Identification of the differential expression of serum microRNA in type 2 diabetes. AB - The identification of disease-specific alterations in miRNA expression and the ability to detect miRNAs in serum furnish the basis for identified potential research value. This study was aimed to characterize the expression of miRNAs in the serum samples from people with type 2 diabetes mellitus (T2DM) and healthy individuals in order to detect the differential expression of miRNAs in T2DM. In total, 582 participants were recruited. Microarray-based miRNA expression profiles were screened in pooled serum samples from two groups (T2DM and healthy control). The candidates' miRNAs were validated by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Five significantly different serum miRNAs were identified in T2DM patients (hsa-miR-320d, hsa-miR 4534, hsa-miR-3960, hsa-miR-451a, and hsa-miR-572) compared to those in the serum of healthy controls. This study provided evidence that serum miRNAs had differential expressions between healthy controls and T2DM patients. These five differential expression miRNAs might be of help for subsequent study in T2DM. PMID- 26554944 TI - Hybrid graphene plasmonic waveguide modulators. AB - The unique optical and electronic properties of graphene make possible the fabrication of novel optoelectronic devices. One of the most exciting graphene characteristics is the tunability by gating which allows one to realize active optical devices. While several types of graphene-based photonic modulators have already been demonstrated, the potential of combining the versatility of graphene with subwavelength field confinement of plasmonic waveguides remains largely unexplored. Here we report fabrication and study of hybrid graphene-plasmonic waveguide modulators. We consider several types of modulators and identify the most promising one for telecom applications. The modulator working at the telecom range is demonstrated, showing a modulation depth of >0.03 dB MUm(-1) at low gating voltages for an active device area of just 10 MUm(2), characteristics which are already comparable to those of silicon-based waveguide modulators while retaining the benefit of further device miniaturization. Our proof-of-concept results pave the way towards on-chip realization of efficient graphene-based active plasmonic waveguide devices for optical communications. PMID- 26554945 TI - Defining the Relationships Among Retinal Function, Layer Thickness and Visual Behavior During Oxidative Stress-Induced Retinal Degeneration. AB - PURPOSE: The purpose of this study was to identify how changes in retinal structure and function correlate with visual deficits during increasing amounts of retinal degeneration. MATERIALS AND METHODS: Retinal degeneration was induced in adult mice by subretinal injections of paraquat (PQ) (0.2-1 mM). Retinal anatomy and photoreceptor layer thickness were quantified by histology and optical coherence tomography (OCT), retinal function was measured using electroretinography (ERG), and visual behavior were measured by optokinetic tracking, at 1 to 3 week post-injury. RESULTS: Photoreceptor layer structure, function and visual behavior declined at a linear rate over time following PQ induced degeneration, with the correlations between outcome measures being lowest at mild injury levels and increasing with injury severity. Overall reductions in visual acuity were highly correlated with declines in retinal thickness (r(2) = 0.78) and function (r(2) = 0.67) and retinal thickness correlated with photoreceptor function (r(2) = 0.72). ERG a-wave scotopic amplitudes showed a stronger correspondence to retinal structure and visual behavior than b-waves. CONCLUSIONS: Measurements of photoreceptor loss at the structural and functional levels showed good correspondence with degeneration-associated changes in visual behavior after oxidative stress injury. The results provide new insight about the relative kinetics of measurements of retinal degeneration induced by oxidative stress, which could guide the choice of optimal outcome measurements for other retinal diseases. PMID- 26554946 TI - Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors. AB - REPLACE is a unique strategy developed to more effectively target protein-protein interactions (PPIs). It aims to expand available drug target space by providing improved methodology for the identification of inhibitors for such binding sites and which represent the majority of potential drug targets. The main goal of this paper is to provide a methodological overview of the use and application of the REPLACE strategy which involves computational and synthetic chemistry approaches. REPLACE is exemplified through its application to the development of non-ATP competitive cyclin dependent kinases (CDK) inhibitors as anti-tumor therapeutics. CDKs are frequently deregulated in cancer and hence are considered as important targets for drug development. Inhibition of CDK2/cyclin A in S phase has been reported to promote selective apoptosis of cancer cells in a p53 independent manner through the E2F1 pathway. Targeting the protein-protein interaction at the cyclin binding groove (CBG) is an approach which will allow the specific inhibition of cell cycle over transcriptional CDKs. The CBG is recognized by a consensus sequence derived from CDK substrates and tumor suppressor proteins termed the cyclin binding motif (CBM). The CBM has previously been optimized to an octapeptide from p21Waf (HAKRRIF) and then further truncated to a pentapeptide retaining sufficient activity (RRLIF). Peptides in general are not cell permeable, are metabolically unstable and therefore the REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) strategy has been applied in order to generate more drug-like inhibitors. The strategy begins with the design of Fragment ligated inhibitory peptides (FLIPs) that selectively inhibit cell cycle CDK/cyclin complexes. FLIPs were generated by iteratively replacing residues of HAKRRLIF/RRLIF with fragment like small molecules (capping groups), starting from the N-terminus (Ncaps), followed by replacement on the C terminus. These compounds are starting points for the generation of non-ATP competitive CDK inhibitors as anti-tumor therapeutics. PMID- 26554947 TI - The adductor magnus "mini-hamstring": MRI appearance and potential pitfalls. AB - OBJECTIVE: To examine the anatomic MRI characteristics of the adductor magnus mini hamstring (AMMH) and explore its involvement in cases of hamstring avulsion. MATERIALS AND METHODS: An IRB-approved retrospective review of patients undergoing "hamstring protocol" MRI between March 2009 and June 2014 was performed. Two musculoskeletal radiologists recorded multiple AMMH anatomic characteristics and involvement in cases of hamstring avulsion. RESULTS: Seventy six AMMHs were analyzed in 66 patients [35 females and 31 males, mean age 49.3 +/ 15.2 years (range 17-81)]. Eleven percent of AMMHs were poorly visualized, 51 % visualized, and 37 % well visualized. Seven percent demonstrated round, 73 % ovoid, and 21 % flat/lenticular tendon morphologies. Most (88 %) demonstrated typical origins. Average cross-sectional area (CSA) was 22.4 +/- 10.6 mm2 (range 6-56), diameter was 7.2 +/- 2.5 mm (range 2.9-15), medial distance from the semimembranosus tendon was 7.5 +/- 2.5 mm (range 3-14), and tendon length was 6.8 +/- 3.3 cm (range 1.2-14.1). There was no gender difference in AMMH anatomic measurements or correlation between age and CSA or diameter. Of 17 complete hamstring avulsion cases, the AMMH was intact in 13, partially torn in 3, and completely torn in 1. CONCLUSION: The AMMH is a constant finding with variable anatomic characteristics. It is visualized or well visualized by MRI in 88 % of cases and is a sizable tendon located in close proximity to the semimembranosus tendon. Because it is uncommonly completely torn (6 %) in cases of complete hamstring avulsion, radiologists should be aware of its presence and appearance to avoid diagnostic confusion. PMID- 26554948 TI - Postpartum sacral insufficiency fractures. AB - Postpartum sacral insufficiency fracture is an uncommon occurrence that is often under-diagnosed because its symptoms of low back, buttock and groin pains may initially be attributed to physiologic biomechanical changes caused by pregnancy or to intervertebral disc disease. We present a case of bilateral sacral insufficiency fractures in a 37-year-old postpartum woman with osteopenic bone mineral density confirmed by dual energy X-ray absorptiometry. The symptoms were initially suspected to be of discogenic cause, and the fractures were incidentally appreciated at the edge of a lumbar spine magnetic resonance image. Therefore, it is important to keep in mind this potential diagnosis when examining imaging studies of postpartum patients. For women who present other risk factors of osteoporosis, imaging of the entire sacrum should be part of the imaging studies. If sacral stress fractures are diagnosed, further evaluation for bone mineral density and underlying metabolic bone disease is recommended. PMID- 26554949 TI - Selenium Deficiency Deteriorate the Inflammation of S. aureus Infection via Regulating NF-kappaB and PPAR-gamma in Mammary Gland of Mice. AB - Selenium (Se) is an essential micronutrient contributing to a strong immune system for the prevention of infections and diseases in humans and animals. Dietary Se regulates the immune status and mediates anti-inflammatory action. Mastitis is an inflammation in the mammary gland typically induced through the major pathogen S. aureus. The aim of the present study was to determine the regulating effect of Se on S. aureus-induced inflammation using a mouse mastitis model. Immunofluorescence staining was used to detect histopathological injury. ELISA was used to detect cytokine expression, while protein and mRNA levels were analyzed through Western blotting and qPCR analysis, respectively. The results showed that Se deficiency increased inflammatory lesions in individuals with S. aureus infection in the mammary gland. The NO levels showed a significant increase in Se-deficient mice with S. aureus mastitis. Se deficiency accelerated the production of pro-inflammatory factors and reduced IL-10 expression. Furthermore, the results of the present study showed that the regulating effect of Se on S. aureus-induced mastitis was associated with the NF-kappaB pathway. Indeed, Se deficiency suppressed PPAR-gamma activity and promoted NF-kappaB pathway activation. Thus, Se supplementation could improve the effect on PPAR gamma and NF-kappaB. These results suggest that Se deficiency could aggravate the inflammatory injury resulting from S. aureus-induced mastitis. Moreover, the results of the present study contribute to the development of new prevention or treatment methods for S. aureus-induced mastitis and other infectious diseases. PMID- 26554950 TI - The Protective Effects of Different Sources of Maternal Selenium on Oxidative Stressed Chick Embryo Liver. AB - The experiment was conducted to investigate the protective effects of different sources of maternal selenium (Se) on oxidative stressed chick embryo. A total of 270 Lingnan Yellow broiler breeders were randomly allocated into three treatments with five replicates for 18 birds each. Breeders were fed with basal diet (BD) including 0.04 mg/kg Se or BD supplemented with sodium selenite (SS) or selenomethionine (SM) at a level of 0.15 mg Se/kg. The rearing experiment lasted for 8 weeks after an 8-week pre-test. Twenty eggs were collected from each replicate during the last 10-day, then incubated in a commercial incubator. On embryonic 17th, fertile eggs were transferred into 39.5 degrees C temperature stimulation for 6 h. Afterward, five eggs were randomly selected from each replicate for collecting chick embryo sample. The results showed that Se supplementation in the diet of breeders resulted in lower reactive oxygen species (ROS), heat shock protein 70 (HSP70), malondialdehyde (MDA), carbonyl and 8 hydroxydeoxyguanosine (8-OHdG) concentrations and higher glutathione peroxidase (GPx), total superoxide dismutase (T-SOD), and catalase (CAT) activities in heat stress treated chick embryo (P < 0.05), and ROS, MDA, carbonyl, 8-OHdG concentrations in SM treatment were lower than those in SS treatment (P < 0.05). Se supplementation elevated cellular glutathione peroxidase (GPx1) mRNA level and activity, cytoplasmic thioredoxin reductase (TrxR1) activity and selenoprotein P (SelP) mRNA and protein level (P < 0.05), and maternal SM showed a higher value than maternal SS in upregulating GPx1, TrxR1, and SelP mRNA levels as well as GPx1 and TrxR1 activities or SelP protein level (P < 0.05). This study indicated that maternal Se can enhance antioxidative capacity and reduce ROS concentration and oxidative damage by upregulating the expression of antioxidative selenoprotein, and maternal SM is superior to SS in heat stress treated chick embryo. PMID- 26554951 TI - Toxicity of Nano-Titanium Dioxide (TiO2-NP) Through Various Routes of Exposure: a Review. AB - Nano-titanium dioxide (TiO2) is one of the most commonly used materials being synthesized for use as one of the top five nanoparticles. Due to the extensive application of TiO2 nanoparticles and their inclusion in many commercial products, the increased exposure of human beings to nanoparticles is possible. This exposure could be routed via dermal penetration, inhalation and oral ingestion or intravenous injection. Therefore, regular evaluation of their potential toxicity and distribution in the bodies of exposed individuals is essential. Keeping in view the potential health hazards of TiO2 nanoparticles for humans, we reviewed the research articles about studies performed on rats or other mammals as animal models. Most of these studies utilized the dermal or skin and the pulmonary exposures as the primary routes of toxicity. It was interesting that only very few studies revealed that the TiO2 nanoparticles could penetrate through the skin and translocate to other tissues, while many other studies demonstrated that no penetration or translocation could happen through the skin. Conversely, the TiO2 nanoparticles that entered through the pulmonary route were translocated to the brain or the systemic circulation from where these reached other organs like the kidney, liver, etc. In most studies, TiO2 nanoparticles appeared to have caused oxidative stress, histopathological alterations, carcinogenesis, genotoxicity and immune disruption. Therefore, the use of such materials in humans must be either avoided or strictly managed to minimise risks for human health in various situations. PMID- 26554952 TI - So much work to do to raise our game on health. PMID- 26554953 TI - Unions call for clarity following dispute over junior doctors' pay. PMID- 26554955 TI - Benefits of 'taste therapy' outlined. PMID- 26554954 TI - Poignant year for nursing as RCN remembers heroic sacrifices. PMID- 26554956 TI - 'Safe' staffing law for Wales expected by early 2016. PMID- 26554957 TI - 'Women are more realistic than men about dementia'. PMID- 26554958 TI - International comparison of health systems casts UK in a dismal light. PMID- 26554959 TI - Activists fight Trade Union Bill. PMID- 26554960 TI - Safety alert issued on the use of hoists. PMID- 26554963 TI - Student raises L 10,000 after pioneering surgery. PMID- 26554961 TI - RCN Wales director calls for close monitoring of 'ambitious targets'. PMID- 26554964 TI - Report reveals 85% of paediatric ICUs have staffing levels shortfall. PMID- 26554965 TI - Learning disability nurses prepare to face the community challenge. PMID- 26554971 TI - Dementia and frailty. PMID- 26554972 TI - Testing times for BRCA gene carriers. PMID- 26554985 TI - Big White Wall app. PMID- 26554973 TI - A helping hand for diabetes care. PMID- 26554986 TI - Don't complicate the nurse's role in delivering medicines to patients. PMID- 26554987 TI - Achievements in dementia care can be celebrated--and shared. PMID- 26554988 TI - Your chance to have a say on the future of nursing education. PMID- 26554989 TI - Proposed changes mean reducing skills, not raising the bar. PMID- 26554990 TI - Nominate your everyday heroes in health care or the community. PMID- 26554993 TI - Fit for purpose--and for my revalidation requirements. PMID- 26554995 TI - How to assess deteriorating patients. PMID- 26554996 TI - Person-centred communication in dementia care. AB - Communication involves the exchange of information between at least two people, a giver and a receiver. If left unaddressed, communication difficulties may have a profound effect on quality of life and quality of care. Poor communication may result in high levels of anxiety and depression for the person living with dementia. Communication breakdown contributes to high rates of depression in spouses of people living with dementia and is a major problem for family and carers. Positive and supportive communication is essential to ensure good quality dementia care. A person-centred approach focuses on supporting a person to use and retain their skills and abilities. Person-centred communication involves a commitment to including the perspective of the person living with dementia, and an understanding of who the person is, their life history and preferences. PMID- 26554997 TI - Assessing fitness to detain in police custody. AB - This article outlines the role of the custody nurse in assessing an individual's fitness to be detained. It addresses all aspects of the assessment, including consent, responsibilities and the structure of the clinical examination. It explores ways to ensure that the detainee's rights and welfare are maintained and their healthcare needs are met. It offers guidance on preparing a care plan for detained individuals that the police can implement. PMID- 26554998 TI - Managing patients with encephalitis. AB - This article provides an overview of encephalitis and addresses its diagnosis, some of the common presenting signs and symptoms, and the different aspects of nursing care required for these patients. In particular, it addresses how to explain encephalitis to the patient's relatives, the rehabilitation needs of these patients, and important aspects of discharge planning. Tests that are necessary for diagnosis in patients with suspected encephalitis and the importance of these are explained. PMID- 26554999 TI - Surgical outcomes. PMID- 26555000 TI - It's better together. PMID- 26555001 TI - Why I now take the global view. PMID- 26555003 TI - From student days to your first shift in charge. PMID- 26555004 TI - Decisional Balance: Alcohol Decisional Balance Intervention for Heavy Drinking Undergraduates. AB - BACKGROUND: This study evaluated a decisional balance intervention among heavy drinking undergraduates and compared a nonweighted decisional balance proportion (DBP; Collins, Carey, & Otto, 2009) to a participant-weighted DBP with weights based on relative importance of items. We expected: (1) the intervention to decrease drinking compared to control; (2) the weighted intervention to be more effective compared to the nonweighted or control in reducing drinking; and (3) intervention efficacy to be moderated by initial DBP. METHOD: Participants (N = 162, Mean age = 24.37, SD = 6.81, 27% male) were randomly assigned to an alcohol intervention wherein they were either asked to assign weights of importance to pros and cons (weighted intervention), or not (nonweighted intervention), or to control. Participants completed web-based questionnaires at baseline and again during a one month follow-up assessment. RESULTS: Consistent with expectations, the nonweighted intervention was associated with reduced follow-up weekly drinking, and the weighted intervention was associated with reductions in drinking frequency. Results further indicated that initial decisional balance did not moderate intervention efficacy. DISCUSSION: Findings suggest that the decisional balance procedure can reduce drinking but there was not compelling evidence for the addition of weights. This study lays the groundwork for enhancing future interventions by increasing empirical knowledge of the role motivation plays in heavy alcohol use. PMID- 26555005 TI - Nanoparticle-mediated radiofrequency capacitive hyperthermia: A phantom study with magnetic resonance thermometry. AB - In hyperthermia, focusing heat generation on tumour tissues and precisely monitoring the temperature around the tumour region is important. To focus heat generation in radiofrequency (RF) capacitive heating, magnetic nanoparticles suspended in sodium carboxymethyl cellulose (CMC) solution were used, based on the hypothesis that the nanoparticle suspension would elevate electrical conductivity and RF current density at the nanoparticle-populated region. A tissue-mimicking phantom with compartments with and without nanoparticles was made for RF capacitive heating experiments. An FDTD model of the phantom was developed to simulate temperature increases at the phantom. To monitor temperature inside the phantom, MR thermometry was performed intermittently during RF heating inside a 3Tesla MRI magnet bore. FDTD simulation on the phantom model was performed in two steps: electromagnetic simulation to compute specific absorption rate and thermal simulation to compute temperature changes. Experimental temperature maps were similar to simulated temperature maps, demonstrating that nanoparticle-populated regions drew more heat than background regions. Nanoparticle-mediated RF heating could mitigate concerns about normal tissue death during RF capacitive hyperthermia. PMID- 26555006 TI - PTEN and PI3K/AKT in non-small-cell lung cancer. AB - Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. In the last years, the identification of activating EGFR mutations, conferring increased sensitivity and disease response to tyrosine kinase inhibitors, has changed the prospect of NSCLC patients. The PTEN/PI3K/AKT pathway regulates multiple cellular functions, including cell growth, differentiation, proliferation, survival, motility, invasion and intracellular trafficking. Alterations in this pathway, mainly PTEN inactivation, have been associated with resistance to EGFR-tyrosine kinase inhibitor therapy and lower survival in NSCLC patients. In this review, we will briefly discuss the main PTEN/PI3K/AKT pathway alterations found in NSCLC, as well as the cell processes regulated by PTEN/PI3K/AKT leading to tumorigenesis. PMID- 26555007 TI - Imposex in the dogwhelk (Nucella lapillus): 22-year monitoring around England and Wales. AB - Six imposex surveys in the dogwhelk (Nucella lapillus) have been conducted over the past two decades to assess legislation effectiveness controlling the use of tri-butyl tin (TBT) by the maritime shipping industry. This study firstly analysed the results of the 2014 survey and secondly carried out a trend assessment of the same 88 sampled sites between 1997 and 2014 of which 65 showed statistically significant reductions. To highlight the magnitude of change, the Vas Deferens Sequence stages (VDS) of the same 56 sites sampled in 1997 and 2010 showed that the Vas Deferens Sequence Index (VDSI) reduced statistically significantly from 2.89 and 0.42, respectively. These data confirm that the legislation enacted, latterly through the International Maritime Organization (IMO) during 2003 to 2008, has been effective in progressively reducing the impact of TBT in the marine environment. Nevertheless, the 2014 results show that two of 18 sampled sites (Gurnard Bay and St. Mawes) are still above the Ecotoxicological Assessment Criteria (EAC) derived for TBT (VDSI <= 2). PMID- 26555008 TI - Copper and cadmium in bottom sediments dredged from Wyscigi Pond, Warsaw, Poland- contamination and bioaccumulation study. AB - This research covered an evaluation of the copper and cadmium concentrations in bottom sediments dredged from one of the ponds in Warsaw. The samples of sediments, soil, and plants were analyzed in terms of Cu and Cd content. The research concerned the heap of dredged bottom sediments from Wyscigi Pond, Warsaw, Poland. Two boreholes were made to obtain sediment cores with depths of A 162.5 cm and B 190.0 cm. The cores were divided into 10 sub-samples with a thickness of about 15-20 cm. A control sample of soil was taken from the horse racecourse several hundred meters away from the heap. The vegetation was sampled directly from the heap. The predominating plants were tested: Urtica dioica, Glechoma hederacea, Euonymus verrucosus, and Drepanocladus aduncus. A control sample of U. dioica taken outside of the heap was also tested. The commercial PHYTOTOXKIT microbiotest was applied to evaluate the influence of heavy metal contaminated sediments (used as soil) on germination and growth of the chosen test plants. The analyses of cadmium and copper concentrations revealed that the metal concentration in sediments was diverse at different depths of sampling, probably reflecting their concentration in stored layers of sediments. Moreover, the metal content in core A was four to five times lower than that in core B, which reveals heterogeneity of the sediments in the tested heap. In core A, the copper concentration ranged from 4.7 to 13.4 mg/kg d.w. (average 8.06 +/- 0.71 mg/kg d.w.), while in core B, it ranged from 9.2 to 82.1 mg/kg d.w. (average 38.56 +/- 2.6 mg/kg d.w.). One of the results of the heavy metal presence in soils is their bioaccumulation in plants. Comparing plant growth, more intensive growth of roots was observed in the case of plants growing on the control (reference) soil than those growing on sediments. The intensive development of both primary and lateral roots was noticed. During this early growth, metal accumulation in plants occurred. PMID- 26555009 TI - Human health risks due to heavy metals through consumption of wild mushrooms from Macheke forest, Rail Block forest and Muganyi communal lands in Zimbabwe. AB - The levels and sources of toxic heavy metals in Amanita loosii (AL) and Cantharellus floridulus (CF) mushrooms and their substrates were studied in some parts of Zimbabwe, Rail Block forest (mining town), Macheke forest (commercial farming), and Muganyi communal lands. The mushrooms and their associated soils were acid digested prior to Al, Pb, and Zn determination by inductively coupled plasma optical emission spectroscopy. The transfer factors, mushrooms-soil metal correlation coefficients, daily intake rates, weekly intake rates, and target hazard quotients were calculated for each metal. The concentration of Zn, Al and Pb in mushrooms ranged from 1.045 +/- 0.028 to 7.568 +/- 0.322, 0.025 +/- 0.001 to 0.654 +/- 0.005, and a maximum of 5.78 +/- 0.31 mg/kg, respectively, in all the three sampling areas. The mean heavy metal concentrations among the three sampling areas decreased as follows: Rail Block forest (mining town) > Macheke forest (commercial farming) > Muganyi communal lands for the concentrations in both mushrooms and total concentration in their substrates. C. floridulus accumulated higher concentrations of Al, Zn, and Pb than A. loosii at each site under study. Zn in both AL and CF (Muganyi communal lands) and Pb in AL (Rail Block forest) were absorbed only from the soils, while other sources of contamination were involved elsewhere. The consumption of 300 g of fresh A. loosii and C. floridulus per day by children less than 16 kg harvested from Rail Block forest would cause health problems, while mushrooms from Macheke Forest and Muganyi communal lands were found to be safe for human consumption. Due to non biodegradability and bioaccumulation abilities of heavy metals, people are discouraged to consume A. loosii and C. floridulus from Rail Block forest for they have significant levels of heavy metals compared to those from Macheke forest and Muganyi communal lands. PMID- 26555010 TI - Time to Death after Terminal Withdrawal of Mechanical Ventilation: Specific Respiratory and Physiologic Parameters May Inform Physician Predictions. AB - BACKGROUND: Discussions about withdrawal of life-sustaining therapies often include family members of critically ill patients. These conversations should address essential components of the dying process, including expected time to death after withdrawal. OBJECTIVES: The study objective was to aid physician communication about the dying process by identifying predictors of time to death after terminal withdrawal of mechanical ventilation. METHODS: We conducted an observational analysis from a single-center, before-after evaluation of an intervention to improve palliative care. We studied 330 patients who died after terminal withdrawal of mechanical ventilation. Predictors included patient demographics, laboratory, respiratory, and physiologic variables, and medication use. RESULTS: The median time to death for the entire cohort was 0.58 hours (interquartile range (IQR) 0.22-2.25 hours) after withdrawal of mechanical ventilation. Using Cox regression, independent predictors of shorter time to death included higher positive end-expiratory pressure (per 1 cm H2O hazard ratio [HR], 1.07; 95% CI 1.04-1.11); higher static pressure (per 1 cm H2O HR, 1.03; 95% CI 1.01-1.04); extubation prior to death (HR, 1.41; 95% CI 1.06-1.86); and presence of diabetes (HR, 1.75; 95% CI 1.25-2.44). Higher noninvasive mean arterial pressure predicted longer time to death (per 1 mmHg HR, 0.98; 95% CI 0.97-0.99). CONCLUSIONS: Comorbid illness and key respiratory and physiologic parameters may inform physician predictions of time to death after withdrawal of mechanical ventilation. An understanding of the predictors of time to death may facilitate discussions with family members of dying patients and improve communication about end-of-life care. PMID- 26555011 TI - Sugar-feeding status alters biting midge photoattraction. AB - The biting midge Culicoides sonorensis Wirth and Jones (Diptera: Ceratopogonidae) transmits pathogens to both livestock and wildlife. Biting midge surveillance relies heavily on light traps for collection; however, little is known about the light spectra preferences of C. sonorensis midges. A light assay arena was constructed and light-emitting diodes (LEDs) of various light spectra were used as light sources to evaluate midge photoattraction. A comparison of responses to light spectra indicated the highest proportions of C. sonorensis were attracted to ultraviolet (UV) light and that midges differentiated 10-nm differences in wavelength. Stronger intensities of UV light resulted in greater attraction. Midges exhibited both sugar-seeking and escape behaviours under different conditions of sugar supplementation before and during the experiment. These behaviours occurred with lights of 355 nm and 365 nm in wavelength. Based on the results of this study, the attraction of C. sonorensis to light traps can be improved through the use of bright LEDs at 355 nm or 365 nm. PMID- 26555012 TI - BMP9/p38 MAPK is essential for the antiproliferative effect of resveratrol on human colon cancer. AB - Colon cancer is one of the most common malignancies of the digestive system. Although more effective therapeutic strategies have been developed in the last decades, there is still a great clinical need to explore new treatment regimens for colon cancer due to the undesirable prognosis. In the present study, we investigated the anticancer activity of resveratrol (Res) in human colon cancer cells, and the possible mechanism underlying this effect. We employed crystal violet staining, flow cytometry and western blotting to test the antiproliferation- and apoptosis-inducing effects of Res in LoVo cells. A xenograft tumor model was also introduced to confirm the in vivo anticancer effect of Res. Using PCR, western blotting, a recombinant adenovirus and a specific inhibitor of p38 MAPK or bone morphogenetic protein receptor (BMPR) to explore the possible molecular mechanisms. We found that Res markedly inhibited the proliferation and promoted the apoptosis of LoVo cells, and suppressed the in vivo tumor growth of colon cancer. Res substantially upregulated the expression of bone morphogenetic protein 9 (BMP9). Exogenous expression of BMP9 enhanced the anticancer effect of Res in LoVo cells, while BMP9 knockdown partly reduced this activity. Res increased the activation of p38 MAPK, which was enhanced by the exogenous expression of BMP9. The anticancer activity of Res, or Res combined with BMP9, was reduced partly by the p38 MAPK inhibitor. The BMPR inhibitor almost abolished the Res-induced activation of p38 MAPK, and attenuated the antiproliferative effect of Res in the LoVo cells. Our findings strongly suggest that the anticancer effect of Res in human colon cancer cells may be partly mediated by upregulation of BMP9 to activate p38 MAPK in a BMPR-dependent manner. PMID- 26555013 TI - Cost-Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis. AB - OBJECTIVE: New opportunities have emerged for early diagnosis with the arrival of new technologies that assess the impact of genomics, proteomics, metabolomics, and cytomics on rheumatoid arthritis (RA) risk. This early health technology assessment study assesses the short-term cost effectiveness of 4 add-on diagnostic tests in early inflammatory arthritis patients at risk of RA. METHODS: We modeled 4 diagnostic add-on tests to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, covering the first year after diagnosis, using Rotterdam Early Arthritis Cohort data. Sensitivity, specificity, and costs were assigned to the magnetic resonance imaging of hands and feet (sensitivity 0.90, specificity 0.60, cost ?756), interleukin-6 (IL-6) serum level test (sensitivity 0.70, specificity 0.53, cost ?50), B cell-related gene expression (sensitivity 0.60, specificity 0.90, cost ?150), and gene assay for RA (sensitivity 0.40, specificity 0.85, cost ?750), based on literature and expert opinion. Outcomes were evaluated using the unweighted diagnostic net benefit (UDNB) and the incremental cost-effectiveness ratio (ICER) in all patients (n = 552), intermediate-risk patients (n = 263), and seronegative patients (n = 329). RESULTS: The highest UDNB was found when using the B cell assay in intermediate-risk patients (43%, ICER ?5,314), while the IL-6 test in seronegative patients resulted in the lowest UDNB (-11.4%, ICER ?7,650). If a threshold of ?20,000 is applied, the B cell assay would be preferred over the other alternatives, with a 78% probability of being cost effective for intermediate-risk patients, 57% for all patients, and 73% for seronegative patients. CONCLUSION: Diagnostic add-on tests favoring specificity over sensitivity with a headroom less than ?370 per test are cost effective, with the largest diagnostic benefit occurring in intermediate-risk patients. PMID- 26555014 TI - Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds. AB - Cell-based systems are useful for discovering antiviral agents. Dissecting the viral life cycle, particularly the early entry stages, allows a mechanistic approach to identify and evaluate antiviral agents that target specific steps of the viral entry. In this report, the methods of examining viral inactivation, viral attachment, and viral entry/fusion as antiviral assays for such purposes are described, using hepatitis C virus as a model. These assays should be useful for discovering novel antagonists/inhibitors to early viral entry and help expand the scope of candidate antiviral agents for further drug development. PMID- 26555016 TI - The NIH Big Data to Knowledge (BD2K) initiative. PMID- 26555017 TI - Center of excellence for mobile sensor data-to-knowledge (MD2K). AB - Mobile sensor data-to-knowledge (MD2K) was chosen as one of 11 Big Data Centers of Excellence by the National Institutes of Health, as part of its Big Data-to Knowledge initiative. MD2K is developing innovative tools to streamline the collection, integration, management, visualization, analysis, and interpretation of health data generated by mobile and wearable sensors. The goal of the big data solutions being developed by MD2K is to reliably quantify physical, biological, behavioral, social, and environmental factors that contribute to health and disease risk. The research conducted by MD2K is targeted at improving health through early detection of adverse health events and by facilitating prevention. MD2K will make its tools, software, and training materials widely available and will also organize workshops and seminars to encourage their use by researchers and clinicians. PMID- 26555019 TI - Moving beyond the physician's EHR. PMID- 26555020 TI - A2 /A2 B to B Renal Transplantation: Past, Present, and Future Directions. AB - One component of the new national kidney allocation system (KAS) in the United States that was implemented on December 4, 2014, was the allocation of kidneys from A2 and A2 B (A, non-A1 and AB, non-A1 B) deceased donors into blood group B candidates (A2 /A2 B -> B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for blood group B candidates on the waiting list, most of whom are minority candidates, we will review the body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also describe prospects for more widespread use of A2 /A2 B -> B transplantation and a novel mechanism of humoral immunosuppression in B patients before and after transplantation with an A2 or A2 B kidney. PMID- 26555018 TI - Trends in biomedical informatics: automated topic analysis of JAMIA articles. AB - Biomedical Informatics is a growing interdisciplinary field in which research topics and citation trends have been evolving rapidly in recent years. To analyze these data in a fast, reproducible manner, automation of certain processes is needed. JAMIA is a "generalist" journal for biomedical informatics. Its articles reflect the wide range of topics in informatics. In this study, we retrieved Medical Subject Headings (MeSH) terms and citations of JAMIA articles published between 2009 and 2014. We use tensors (i.e., multidimensional arrays) to represent the interaction among topics, time and citations, and applied tensor decomposition to automate the analysis. The trends represented by tensors were then carefully interpreted and the results were compared with previous findings based on manual topic analysis. A list of most cited JAMIA articles, their topics, and publication trends over recent years is presented. The analyses confirmed previous studies and showed that, from 2012 to 2014, the number of articles related to MeSH terms Methods, Organization & Administration, and Algorithms increased significantly both in number of publications and citations. Citation trends varied widely by topic, with Natural Language Processing having a large number of citations in particular years, and Medical Record Systems, Computerized remaining a very popular topic in all years. PMID- 26555021 TI - Degradation of host ubiquitin E3 ligase Itch by human cytomegalovirus UL42. AB - Human cytomegalovirus (HCMV) UL42 is classified as a CMV-specific but function unknown gene. According to its amino acid sequence, UL42 has a C-terminal hydrophobic domain predicted to be a transmembrane domain and two PPxY (PY) motifs in its N terminus, but no N-terminal signal peptide. These features resemble those of herpes simplex virus (HSV) UL56 and varicella-zoster virus ORF0. HCMV UL42 interacts with Itch, a member of the Nedd4 family of ubiquitin E3 ligases, through its PY motifs as observed in HSV UL56. HCMV UL42 was partially colocalized with the trans-Golgi network and cytoplasmic vesicles in transfected fibroblasts. Itch was colocalized with HCMV UL42 and accumulated in a fine speckled pattern in the cytoplasm. UL42 induced the ubiquitination and degradation of Itch in HCMV-infected fibroblasts, and was partially colocalized with p62, a ubiquitin-binding protein, and CD63, a marker of lysosome and multivesicular bodies. The electrophoretic pattern of Itch was altered by infection with HCMV and the amount of Itch was increased by the deletion of UL42. Our findings suggest that the regulatory function of the Nedd4 E3 ligase family and the structural features of HCMV UL42 are conserved characteristics in herpesviruses. PMID- 26555022 TI - Event-related potential correlates of processing alcohol-related pictures in young adult binge drinkers. AB - BACKGROUND: Alcohol-dependent individuals exhibit dissociable event-related potential (ERP) responses to alcohol-related cues. Fewer studies have examined if similar effects can be found in non-dependent young adults who binge drink. OBJECTIVES: To delineate the neurocognitive correlates of inhibiting behavioral responses to alcoholic and non-alcoholic beverage cues in social drinkers with differing numbers of binge episodes and instances of intoxication. METHODS: ERP data were acquired while 50 participants performed a Go/No-go paradigm consisting of shapes and pictures of alcoholic and non-alcoholic beverages. Behavioral and self-report data were also collected. RESULTS: We grouped participants into those with: 0 binge episodes, 1 <= 5 binge episodes, and >= 8 episodes. Across participants, alcohol images elicited reduced N200 components and a more positive late slow-wave than non-alcoholic images. While the group with the higher number of binge episodes exhibited altered N100 amplitudes and both groups of binge drinkers exhibited minor differences in P300 topography, these effects were not specifically related to processing alcohol images. However, participants with greater instances of intoxication exhibited an enhanced N200 to alcoholic stimuli compared to individuals with fewer instances of intoxication. This effect was correlated with subjective ratings of alcoholic beverage images. CONCLUSIONS: These data suggest that binge drinking, particularly more severe binge drinking, is associated with functional modifications of cortical systems related to attentional control. Further, the data suggest that young adult social drinkers with riskier patterns of alcohol use (greater instances of intoxication) require the allocation of increased cortical resources to successfully inhibit responses to alcohol-related cues. PMID- 26555023 TI - Cobalt-Catalyzed Alkenylzincation of Unfunctionalized Alkynes. AB - While transition metal catalyzed addition reactions of arylmetal reagents to unfunctionalized alkynes have been extensively developed in the last decade, analogous reactions using alkenylmetal reagents remain rare regardless of their potential utility for the synthesis of unsymmetrical 1,3-dienes. Reported herein is the development of a cobalt/diphosphine catalyst which promotes efficient and stereoselective addition of alkenylzinc reagents to unfunctionalized internal alkynes. The resulting dienylzinc species serve as versatile intermediates for further synthetic transformations. PMID- 26555024 TI - How Long Is Safe? Setting the Cutoff for Uncomplicated Third Stage Length: A Retrospective Case-Control Study. AB - OBJECTIVE: The aim of our study was to determine the optimal time for manual placental removal in an uncomplicated third stage while taking into consideration the risk for blood transfusion. Risk factors for postpartum blood transfusions were studied. METHODS: Computerized data of all vaginal deliveries at our labor and delivery unit from 2010 to 2014 were obtained. Cases of complete and spontaneous placental separation up to 60 minutes into the third stage of labor were extracted for analysis. Patient demographics, obstetrical history, delivery course, and outcome were assessed as well as blood product requirements during the postpartum period. Receiver-operating curves (ROC) for prediction of blood transfusion during the third stage were calculated and risk factors were assessed. RESULTS: 31,226 vaginal deliveries occurred during the study period and 28,586 deliveries culminated with complete and spontaneous placental separation, 25,160 of which met inclusion criteria. Independent risk factors for blood transfusions were primiparity, longer second and third stage length, labor induction, and maternal intrapartum fever. ROC curves showed that the optimal cutoff for the prediction of blood transfusions was 17 minutes into the third stage of labor. Waiting more than 30 minutes for placental separation increases the risk for blood transfusion more than threefold. CONCLUSIONS: A third stage longer than 17 minutes is associated with an increased risk for blood transfusion postpartum. After more than 30 minutes, the risk for blood transfusions increases more than threefold. PMID- 26555026 TI - Editorial: Pain Relief in Osteoarthritis: The Potential for a Perfect Storm. PMID- 26555025 TI - Validation of methods for assessing cardiovascular disease using electronic health data in a cohort of Veterans with diabetes. AB - BACKGROUND: Electronic health data are routinely used to conduct studies of cardiovascular disease in the setting of the Veterans Health Administration (VA). Previous studies have estimated the positive predictive value (PPV) of International Classification of Disease, Ninth Revision (ICD-9) codes for acute myocardial infarction (MI), but the sensitivity of these codes for all true events and the accuracy of coding algorithms for prevalent disease status at baseline are largely unknown. METHODS: We randomly sampled 180 Veterans from the VA Puget Sound Health Care System who initiated diabetes treatment. The full electronic medical record was reviewed to identify prevalent conditions at baseline and acute MI events during follow-up. The accuracy of various coding algorithms was assessed. RESULTS: Algorithms for previous acute events at baseline had high PPV (previous MI: 97%; previous stroke: 81%) but low sensitivity (previous MI: 38%; previous stroke: 52%). Algorithms for chronic conditions at baseline had high PPV (heart failure: 72%; coronary heart disease [CHD]: 85%) and high sensitivity (heart failure: 90%, CHD: 84%). For current smoking status at baseline, ICD-9 codes with pharmacy data had a PPV of 77% and sensitivity of 73%. The coding algorithm for acute MI events during follow-up had high PPV (80%) and sensitivity (89%). CONCLUSIONS: ICD-9 codes for acute MI events during follow-up had high PPV and sensitivity. The sensitivity of ICD-9 codes for previous acute events at baseline was low, but a composite variable for baseline CHD had good accuracy. PMID- 26555027 TI - Circulating and myometrial markers of oxidative stress in pregnant women with fetal growth restriction. AB - AIM: The objective of this study was to identify the relationship between fetal growth restriction (FGR) and oxidative stress. The mechanisms that protect against oxidative stress in the local microenvironment were investigated by comparing the activities of the markers, both in the circulation and myometrium. MATERIALS AND METHODS: Myometrial tissue and serum levels of malondialdehyde (MDA), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) markers were measured in 20 FGR and 20 healthy pregnancies. RESULTS: The mean duration of gestation at delivery was shorter (P = 0003) and the mean birthweight was lower P < 0001) in the FGR study group compared with the control group, as expected. While MDA and CAT concentrations were higher in the serum (P < 0.02 and P < 0.01, respectively), but lower in the myometrial samples (P < 0.01) in the FGR versus the control group, XO and myometrial SOD values were comparable in both groups. CONCLUSIONS: Although our data demonstrated that FGR is associated with oxidative stress, the exact role and mechanism of the oxidant and antioxidant imbalance is obscure. We speculate that despite limited local synthesis of CAT, effective and efficient removal of MDA in the uterine environment explains high MDA and CAT serum concentrations in women with FGR. Alternatively, a well-functioning myometrial system could rescue the fetus from reactive oxygen species, as demonstrated by lowered MDA and depleted CAT resulting from hyperconsumption. Elevated serum MDA and CAT levels in the serum may reflect the 'spillover' of these markers from the uterus to the circulation. PMID- 26555028 TI - Diagnostic Accuracy of Aortic Root Cross-sectional Area/Height Ratio in Children and Young Adults with Marfan and Loeys-Dietz Syndrome. AB - BACKGROUND: Accurate quantification of aortic dilatation is critical in children with syndromes associated with thoracic aortic aneurysm, yet classification of normality is difficult. Current methods of normalization use body surface area to account for growth, despite a nonlinear relationship of body surface area to aortic root dimensions. In contrast, height has a linear relationship with aortic root dimensions in normal children, is simple to measure and requires no secondary calculation. We evaluated the diagnostic accuracy of an height-based aortic root-indexing method, aortic root cross-sectional area/height ratio (AHr), in children with Marfan and Loeys-Dietz syndromes. METHODS: A cohort of 54 children with Marfan or Loeys-Dietz syndromes, aged 3 months to 17 years, were evaluated with a transthoracic echocardiogram. AHr was measured in diastole at sinuses of Valsalva (SoV) and proximal ascending aorta (pAA) in a group of normal subjects matched for age and body surface area and normal values were provided. AHr values were recorded for patients and compared with z-scores results obtained with Gautier's and Campens's nomograms. RESULTS: AHr values in the group of normal subjects were 2.6 +/- 0.6 at SoV and 2 +/- 0.5 at pAA. Categorization of z scores and AHr showed good correspondence between AHr and Gautier's method (P = .341 at SoV and .185 at pAA) and AHr and Campens method (P =.465 at SoV and 0.110 at pAA). CONCLUSIONS: There was a good correspondence of AHr results with two different z-scores. AHr is a simple to use and valid option to quantify aortic root dilatation in pediatric patients. PMID- 26555030 TI - Flexible synthesis of polyfunctionalised 3-fluoropyrroles. AB - An efficient and selective approach for the synthesis of polyfunctionalised 3 fluoropyrroles has been developed starting from commercial aldehydes. The methodology is concise, efficient and allows for the modular and systematic assembly of polysubstituted 3-fluoropyrroles. This synthesis provides an alternative and highly convergent strategy for the generation of these chemically and biologically important units. PMID- 26555029 TI - Cerebral palsy after neonatal encephalopathy: do neonates with suspected asphyxia have worse outcomes? AB - AIM: We sought to investigate how brain injury and severity, and neurological subtype of cerebral palsy (CP) differed in term-born children with CP after neonatal encephalopathy, between those with suspected birth asphyxia and those without. METHOD: Using the Canadian CP Registry, which included 1001 children, those with CP born at >= 36 wks after moderate or severe neonatal encephalopathy, were dichotomized according to the presence or absence of suspected birth asphyxia. Gross Motor Function Classification System (GMFCS) scores, neurological subtypes, comorbidities, and magnetic resonance imaging findings were compared. RESULTS: Of the 147 term-born children with CP (82 males, 65 females; median age 37 months, interquartile range [IQR] 26-52.5) who after moderate or severe neonatal encephalopathy had the required outcome data, 61 (41%) met criteria for suspected birth asphyxia. They had a higher frequency of non-ambulatory GMFCS status (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.72-6.8), spastic quadriplegia (OR 2.8, 95% CI 1.4-5.6), non-verbal communication skills impairment (OR 4.2, 95% CI 2.0-8.6), isolated deep grey matter injury (OR 4.1, 95% CI 1.8 9.5), a lower frequency of spastic hemiplegia (OR 0.17, 95% CI 0.07-0.42), focal injury (OR 0.20; 95% CI 0.04-0.93), and more comorbidities (p=0.017) than those who did not meet criteria. INTERPRETATION: Term-born children who develop CP after neonatal encephalopathy with suspected birth asphyxia have a greater burden of disability than those without suspected birth asphyxia. PMID- 26555031 TI - Risk of idiopathic normal pressure hydrocephalus in older inpatients with schizophrenia. AB - BACKGROUND: The mean age of inpatients with schizophrenia has gradually increased in Japan and the risk of fracture in older schizophrenia patients is elevated. One possible cause may be idiopathic normal pressure hydrocephalus (iNPH). The present study aimed to evaluate the prevalence and symptoms of iNPH in older inpatients with schizophrenia. METHODS: We prospectively examined older inpatients with schizophrenia (N = 21, mean age = 70.5 +/- 5.9) in a psychiatric ward. We evaluated iNPH symptoms using the idiopathic Normal-Pressure Hydrocephalus Grading Scale (iNPHGS), Timed Up-and-Go test (TUG), Gait Status Scale (GSS), Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI). We also evaluated symptoms of schizophrenia using the Brief Psychiatric Rating Scale (BPRS) and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). We conducted cerebrospinal fluid (CSF) tap tests for patients with possible-iNPH. RESULTS: In total, three (14.3%) patients were diagnosed with possible iNPH: age, GS-Gait, GS-Cognition, TUG, 10-meter walking test, GSS, and DIEPSS were significantly increased in these compared to patients without iNPH; however, GS Urine, MMSE, NPI, and BPRS did not differ significantly. Probable iNPH was diagnosed for two (9.5%) patients because of positive CSF tap tests. CONCLUSION: The prevalence of possible and probable iNPH in older patients with schizophrenia was much higher than that reported for older people without mental illness. Of the symptoms evaluated with the tests employed, only gait disturbances, particularly walking speed, distinguished schizophrenia patients with iNPH. These findings suggest that we should pay more attention to the possibility of iNPH in older patients with schizophrenia. PMID- 26555033 TI - Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected. AB - Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy. PMID- 26555032 TI - Multiple genomic signatures of selection in goats and sheep indigenous to a hot arid environment. AB - Goats and sheep are versatile domesticates that have been integrated into diverse environments and production systems. Natural and artificial selection have shaped the variation in the two species, but natural selection has played the major role among indigenous flocks. To investigate signals of natural selection, we analyzed genotype data generated using the caprine and ovine 50K SNP BeadChips from Barki goats and sheep that are indigenous to a hot arid environment in Egypt's Coastal Zone of the Western Desert. We identify several candidate regions under selection that spanned 119 genes. A majority of the genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes. In particular, selection signatures spanning several genes that directly or indirectly influenced traits for adaptation to hot arid environments, such as thermo-tolerance (melanogenesis) (FGF2, GNAI3, PLCB1), body size and development (BMP2, BMP4, GJA3, GJB2), energy and digestive metabolism (MYH, TRHDE, ALDH1A3), and nervous and autoimmune response (GRIA1, IL2, IL7, IL21, IL1R1) were identified. We also identified eight common candidate genes under selection in the two species and a shared selection signature that spanned a conserved syntenic segment to bovine chromosome 12 on caprine and ovine chromosomes 12 and 10, respectively, providing, most likely, the evidence for selection in a common environment in two different but closely related species. Our study highlights the importance of indigenous livestock as model organisms for investigating selection sweeps and genome-wide association mapping. PMID- 26555034 TI - A novel dual-glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist is neuroprotective in transient focal cerebral ischemia in the rat. AB - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP 1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL). Animals were evaluated for neurologic deficit score, infarct volume, and immunohistochemical analyses of the brain at several time points after ischemia. The Val(8)-GLP-1(glu-PAL)-treated and DA-treated groups showed significantly reduced scores of neurological dysfunction, cerebral infarction size, and percentage of TUNEL-positive apoptotic neurons. Furthermore, the expression of the apoptosis marker Bax, the inflammation marker iNOS, and the survival marker Bcl-2 was significantly increased. The DA-treated group was better protected against neurodegeneration than the Val(8)-GLP-1(glu-PAL) group, and the scores of neurological dysfunction, cerebral infarction size, and expression of Bcl-2 were higher, whereas the percentage of TUNEL-positive neurons and the levels of Bax and iNOS were lower in the DA group. DA treatment reduced the infarct volume and improved the functional deficit. It also suppressed the inflammatory response and cell apoptosis after reperfusion. In conclusion, the novel GIP and GLP-1 dual-receptor agonist is more neuroprotective than a GLP-1 receptor agonist in key biomarkers of neuronal degeneration. PMID- 26555035 TI - Possibility of a sex-specific role for a genetic variant in FRMPD4 in schizophrenia, but not cognitive function. AB - The neurotransmitter disturbances responsible for cognitive dysfunction in schizophrenia are hypothesized to originate with alterations in postsynaptic scaffold proteins. We have recently reported that protein levels of FRMPD4, a multiscaffolding protein that modulates both Homer1 and postsynaptic density protein 95 activity, is altered in the schizophrenia postmortem brain, in regions involved in cognition. Here, we set out to investigate whether genetic variation in FRMPD4 is associated with cognitive function in people with schizophrenia. We selected and examined a novel single nucleotide polymorphism, rs5979717 (positioned in the noncoding 3' untranslated region of FRMPD4 and potentially influencing protein expression), for its association with schizophrenia and nine measures of cognitive function, using age-matched and sex-matched samples from 268 schizophrenia cases and 268 healthy controls. Brain samples from 20 schizophrenia patients and 20 healthy controls were additionally genotyped to study the influence of this variant on protein expression of FRMPD4. Allelic distribution of rs5979717 was associated with schizophrenia in females (chi=4.52, P=0.030). No effects of rs5979717 were observed on cognitive performance, nor an influence of rs5979717 genotypes on the expression of FRMPD4 proteins in postmortem brain samples. These data provide initial support for a sex-specific role for common variation in rs5979717 in schizophrenia, which now warrants further investigation. PMID- 26555037 TI - WSe2 Light-Emitting Tunneling Transistors with Enhanced Brightness at Room Temperature. AB - Monolayers of molybdenum and tungsten dichalcogenides are direct bandgap semiconductors, which makes them promising for optoelectronic applications. In particular, van der Waals heterostructures consisting of monolayers of MoS2 sandwiched between atomically thin hexagonal boron nitride (hBN) and graphene electrodes allows one to obtain light emitting quantum wells (LEQWs) with low temperature external quantum efficiency (EQE) of 1%. However, the EQE of MoS2- and MoSe2-based LEQWs shows behavior common for many other materials: it decreases fast from cryogenic conditions to room temperature, undermining their practical applications. Here we compare MoSe2 and WSe2 LEQWs. We show that the EQE of WSe2 devices grows with temperature, with room temperature EQE reaching 5%, which is 250* more than the previous best performance of MoS2 and MoSe2 quantum wells in ambient conditions. We attribute such different temperature dependences to the inverted sign of spin-orbit splitting of conduction band states in tungsten and molybdenum dichalcogenides, which makes the lowest-energy exciton in WSe2 dark. PMID- 26555036 TI - Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis. AB - BACKGROUND: Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. METHODS: Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. RESULTS: The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. CONCLUSIONS: For the first time this data associates altered CDK5 substrate phosphorylation with oncogenesis in some but not all tumour types, implicating altered CDK5 activity in aspects of pathogenesis. These data identify a novel oncogenic mechanism where CDK5 activation induces CRMP2A phosphorylation in the nuclei of tumour cells. PMID- 26555038 TI - Bacterial prostatitis. AB - PURPOSE OF REVIEW: The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. RECENT FINDINGS: Cross sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. SUMMARY: Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated. PMID- 26555040 TI - New players in the preventive treatment of migraine. AB - Migraine is a common, chronic disorder of the brain causing much disability, as well as personal, familial and societal impact. Several oral preventive agents are available in different countries for the prevention of migraine, but none have performed better than 50% improvement in 50% of patients in a clinical trial. Additionally, each has various possible adverse events making their tolerability less than optimal. Recently, three monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) ligand (LY2951742, ALD403 and TEV 48125) and one targeting the CGRP receptor (AMG 334) have completed phase 2 trials, and the results have been reported. These early results show them all to be somewhat more effective than placebo, with no serious adverse events. Three have been studied for episodic migraine, and only TEV-48125 has been studied for both high frequency episodic and chronic migraine. Moreover, preliminary data suggests that neurostimulation is effective in migraine treatment, including stimulation of the sphenopalatine ganglion, transcutaneous supraorbital and supratrochlear nerve, and transcutaneous vagus nerve. In this article, these innovative therapies will be reviewed. PMID- 26555039 TI - Maintaining lung health with longstanding HIV. AB - PURPOSE OF REVIEW: Human immunodeficiency virus (HIV) is now managed as a chronic disease. Non-infectious pulmonary conditions have replaced infection as the biggest threat to lung health, particularly as HIV cohorts age, but there is no consensus on how best to maintain long-term lung health. We review the epidemiology and pathogenesis of chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), and lung cancer in HIV-seropositive individuals. RECENT FINDINGS: Diagnoses of COPD are now up to 50% more prevalent in HIV-seropositive individuals than HIV-uninfected controls, and prospective pulmonary function studies find significant impairment in 7% to more than 50% of HIV-seropositive individuals. The prevalence of HIV-PAH is 0.2-0.5%, and lung cancer is two to three times more prevalent in HIV-seropositive individuals. Although host factors such as age and smoking have a role, HIV is an independent contributor to the pathogenesis of COPD, PAH, and lung cancer. Chronic inflammation, immune senescence, oxidative stress, and direct effects of viral proteins are all potential pathogenetic mechanisms. Despite their prevalence, non infectious lung diseases remain underrecognized and evidence for effective screening strategies in HIV-seropositive individuals is limited. SUMMARY: COPD, PAH, and lung cancer are a growing threat to lung health in the highly active antiretroviral therapy era necessitating early recognition. PMID- 26555041 TI - Development of a Highly Potent D2/D3 Agonist and a Partial Agonist from Structure Activity Relationship Study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl) N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Implication in the Treatment of Parkinson's Disease. AB - Our structure-activity relationship studies with N(6)-(2-(4-(1H-indol-5 yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6 diamine derivatives led to development of a lead compound (-)-21a which exhibited very high affinity (Ki, D2 = 16.4 nM, D3 = 1.15 nM) and full agonist activity (EC50 (GTPgammaS); D2 = 3.23 and D3 = 1.41 nM) at both D2 and D3 receptors. A partial agonist molecule (-)-34 (EC50 (GTPgammaS); D2 = 21.6 (Emax = 27%) and D3 = 10.9 nM) was also identified. In a Parkinson's disease (PD) animal model, (-) 21a was highly efficacious in reversing hypolocomotion in reserpinized rats with a long duration of action, indicating its potential as an anti-PD drug. Compound (-)-34 was also able to elevate locomotor activity in the above PD animal model significantly, implying its potential application in PD therapy. Furthermore, (-) 21a was shown to be neuroprotective in protecting neuronal PC12 from toxicity of 6-OHDA. This report, therefore, underpins the notion that a multifunctional drug like (-)-21a might have the potential not only to ameliorate motor dysfunction in PD patients but also to modify disease progression by protecting DA neurons from progressive degeneration. PMID- 26555043 TI - Lewis Acid Binding and Transfer as a Versatile Experimental Gauge of the Lewis Basicity of Fe(0) , Ru(0) , and Pt(0) Complexes. AB - A number of zerovalent ruthenium tri- and tetracarbonyl complexes of the form [Ru(CO)5-n Ln] (n=1, 2) with neutral phosphine or N-heterocyclic carbene donor ligands have been treated with the Lewis acids GaCl3 and Ag(+) to form a range of metal-only Lewis pairs (MOLPs). The spectroscopic and structural parameters of the adducts are compared to each other and to related iron carbonyl based MOLPs. The Lewis basicity of the original Ru(0) complexes is gauged by transfer experiments, as well as through the degree of pyramidization of the bound GaCl3 units and the Ru-M bond lengths. The work shows the benefits of the MOLP concept as one of the few direct experimental gauges of metal basicity, and one that can allow comparisons between metal complexes with different metal centers and ligand sets. PMID- 26555042 TI - Cytoplasmic Dynein Antagonists with Improved Potency and Isoform Selectivity. AB - Cytoplasmic dyneins 1 and 2 are related members of the AAA+ superfamily (ATPases associated with diverse cellular activities) that function as the predominant minus-end-directed microtubule motors in eukaryotic cells. Dynein 1 controls mitotic spindle assembly, organelle movement, axonal transport, and other cytosolic, microtubule-guided processes, whereas dynein 2 mediates retrograde trafficking within motile and primary cilia. Small-molecule inhibitors are important tools for investigating motor protein-dependent mechanisms, and ciliobrevins were recently discovered as the first dynein-specific chemical antagonists. Here, we demonstrate that ciliobrevins directly target the heavy chains of both dynein isoforms and explore the structure-activity landscape of these inhibitors in vitro and in cells. In addition to identifying chemical motifs that are essential for dynein blockade, we have discovered analogs with increased potency and dynein 2 selectivity. These antagonists effectively disrupt Hedgehog signaling, intraflagellar transport, and ciliogenesis, making them useful probes of these and other cytoplasmic dynein 2-dependent cellular processes. PMID- 26555044 TI - Transformation of Step-Growth Polymerization into Living Chain-Growth Polymerization. PMID- 26555045 TI - Out of the Mouth of Minnows. AB - The skeleton articulates at specialized junctions, or joints. Although many factors that specify joints are known, how these different mechanisms are integrated to define the joint remains unclear. In this issue of Developmental Cell, Askary et al. (2015) utilize zebrafish to identify genetic regulatory mechanisms of joint specification and differentiation. PMID- 26555046 TI - Linking Nutrients to Growth through a Positive Feedback Loop. AB - In this issue of Developmental Cell, Okamoto and Nishimura (2015) identify a positive feedback loop between neuronal cells that maintains insulin signaling and growth under restricted nutritional conditions. PMID- 26555047 TI - Different Species Choose Their Own Paths to Pluripotency. AB - Pluripotency is well defined functionally but ambiguously defined at the molecular level. In this issue of Developmental Cell, Boroviak and colleagues (2015) use a multi-species approach to differentiate between fundamental features of pluripotency in mammals and those that exhibit evolutionary plasticity. PMID- 26555050 TI - Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth. AB - The insulin-like peptide (ILP) family plays key biological roles in the control of body growth. Although the functions of ILPs are well understood, the mechanisms by which organisms sense their nutrient status and thereby control ILP production remain largely unknown. Here, we show that signaling relay and feedback mechanisms control the nutrient-dependent expression of Drosophila ILP5 (Dilp5). The expression of dilp5 in brain insulin-producing cells (IPCs) is negatively regulated by the transcription factor FoxO. Glia-derived Dilp6 remotely regulates the FoxO activity in IPCs, primarily through Jeb secreted by cholinergic neurons. Dilp6 production by surface glia is amplified by cellular response to circulating Dilps derived from IPCs, in concert with amino acid signals. The induction of dilp5 is critical for sustaining body growth under restricted food conditions. These results provide a molecular framework that explains how the production of an endocrine hormone in a specific tissue is coordinated with environmental conditions. PMID- 26555049 TI - An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis. AB - Actin polymerization powers membrane deformation during many processes, including clathrin-mediated endocytosis (CME). During CME in yeast, actin polymerization is triggered and coordinated by a six-protein WASP/Myosin complex that includes WASP, class I myosins (Myo3 and Myo5), WIP (Vrp1), and two other proteins. We show that a single engineered protein can replace this entire complex while still supporting CME. This engineered protein reveals that the WASP/Myosin complex has four essential activities: recruitment to endocytic sites, anchorage to the plasma membrane, Arp2/3 activation, and transient actin filament binding by the motor domain. The requirement for both membrane and F-actin binding reveals that myosin-mediated coupling between actin filaments and the base of endocytic sites is essential for allowing actin polymerization to drive membrane invagination. PMID- 26555048 TI - E Proteins and ID Proteins: Helix-Loop-Helix Partners in Development and Disease. AB - The basic Helix-Loop-Helix (bHLH) proteins represent a well-known class of transcriptional regulators. Many bHLH proteins act as heterodimers with members of a class of ubiquitous partners, the E proteins. A widely expressed class of inhibitory heterodimer partners-the Inhibitor of DNA-binding (ID) proteins-also exists. Genetic and molecular analyses in humans and in knockout mice implicate E proteins and ID proteins in a wide variety of diseases, belying the notion that they are non-specific partner proteins. Here, we explore relationships of E proteins and ID proteins to a variety of disease processes and highlight gaps in knowledge of disease mechanisms. PMID- 26555051 TI - Integration of Light and Photoperiodic Signaling in Transcriptional Nuclear Foci. AB - Light regulates major plant developmental transitions by orchestrating a series of nuclear events. This study uncovers the molecular function of the natural variant, TZP (Tandem Zinc-finger-Plus3), as a signal integrator of light and photoperiodic pathways in transcriptional nuclear foci. We report that TZP acts as a positive regulator of photoperiodic flowering via physical interactions with the red-light receptor phytochrome B (phyB). We demonstrate that TZP localizes in dynamic nuclear domains regulated by light quality and photoperiod. This study shows that phyB is indispensable not only for localizing TZP to transcriptionally active nuclear photobodies, but also for recruiting TZP on the promoter of the floral inducer FLOWERING LOCUS T (FT). Our findings signify a unique transcriptional regulatory role to the highly enigmatic plant nuclear photobodies, where TZP directly activates FT gene expression and promotes flowering. PMID- 26555053 TI - Polarization of PI3K Activity Initiated by Ooplasmic Segregation Guides Nuclear Migration in the Mesendoderm. AB - Asymmetric localization of RNA is a widely observed mechanism of cell polarization. Using embryos of the ascidian, Halocynthia roretzi, we previously showed that mesoderm and endoderm fates are separated by localization of mRNA encoding a transcription factor, Not, to the future mesoderm-side cytoplasm of the mesendoderm cell through asymmetric positioning of the nucleus. Here, we investigated the mechanism that defines the direction of the nuclear migration. We show that localization of PtdIns(3,4,5)P3 to the future mesoderm region determines the direction of nuclear migration. Localization of PtdIns(3,4,5)P3 was dependent on the localization of PI3Kalpha to the future mesoderm region. PI3Kalpha was first localized at the 1-cell stage by the ooplasmic movement. Activity of localized PI3Kalpha at the 4-cell stage was required for the localization of PI3Kalpha up to the nuclear migration. Our results provide the scaffold for understanding the chain of causality leading to the separation of germ layer fates. PMID- 26555052 TI - FGF-Regulated ETV Transcription Factors Control FGF-SHH Feedback Loop in Lung Branching. AB - The mammalian lung forms its elaborate tree-like structure following a largely stereotypical branching sequence. While a number of genes have been identified to play essential roles in lung branching, what coordinates the choice between branch growth and new branch formation has not been elucidated. Here we show that loss of FGF-activated transcription factor genes, Etv4 and Etv5 (collectively Etv), led to prolonged branch tip growth and delayed new branch formation. Unexpectedly, this phenotype is more similar to mutants with increased rather than decreased FGF activity. Indeed, an increased Fgf10 expression is observed, and reducing Fgf10 dosage can attenuate the Etv mutant phenotype. Further evidence indicates that ETV inhibits Fgf10 via directly promoting Shh expression. SHH in turn inhibits local Fgf10 expression and redirects growth, thereby initiating new branches. Together, our findings establish ETV as a key node in the FGF-ETV-SHH inhibitory feedback loop that dictates branching periodicity. PMID- 26555054 TI - Global Analysis of mRNA, Translation, and Protein Localization: Local Translation Is a Key Regulator of Cell Protrusions. AB - Polarization of cells into a protrusive front and a retracting cell body is the hallmark of mesenchymal-like cell migration. Many mRNAs are localized to protrusions, but it is unclear to what degree mRNA localization contributes toward protrusion formation. We performed global quantitative analysis of the distributions of mRNAs, proteins, and translation rates between protrusions and the cell body by RNA sequencing (RNA-seq) and quantitative proteomics. Our results reveal local translation as a key determinant of protein localization to protrusions. Accordingly, inhibition of local translation destabilizes protrusions and inhibits mesenchymal-like morphology. Interestingly, many mRNAs localized to protrusions are translationally repressed. Specific cis-regulatory elements within mRNA UTRs define whether mRNAs are locally translated or repressed. Finally, RNAi screening of RNA-binding proteins (RBPs) enriched in protrusions revealed trans-regulators of localized translation that are functionally important for protrusions. We propose that by deciphering the localized mRNA UTR code, these proteins regulate protrusion stability and mesenchymal-like morphology. PMID- 26555055 TI - Iroquois Proteins Promote Skeletal Joint Formation by Maintaining Chondrocytes in an Immature State. AB - An early event in skeletal joint development is the specification of articular chondrocytes at the joint surface. Articular chondrocytes are distinct in producing lower levels of cartilage matrix and not being replaced by bone, yet how they acquire these properties remains poorly understood. Here, we show that two members of the Iroquois transcriptional repressor family, Irx7 and Irx5a, function to block chondrocyte maturation at the developing hyoid joint of zebrafish. These Irx factors suppress the production of cartilage matrix at the joint in part by preventing the activation of a col2a1a enhancer by Sox9a. Further, both zebrafish Irx7 and mouse IRX1 are able to repress cartilage matrix production in a murine chondrogenic cell line. Iroquois proteins may therefore have a conserved role in keeping chondrocytes in an immature state, with the lower levels of cartilage matrix produced by these immature cells contributing to joint flexibility. PMID- 26555058 TI - Non-Sequential Spectral Acquisitions and Data Reconstruction to Remove Time Dependent Effects from X-Ray Spectra. AB - X-ray spectroscopy techniques may require prolonged exposure of a sample to an electron beam to generate X-rays. With typical spectroscopic methods the measured signal is acquired while varying the independent parameter in a systematic way, for example, stepping a photon detector in a series of energy steps from one end of the range of interest to the other incrementally or varying the energy of the incoming excitation incrementally. This can be a time-consuming process when signal strength is low, and if the sample is affected by prolonged beam exposure it could potentially change the shape and position of the obtained X-ray spectrum. Hydrocarbon contamination is of particular concern in electron beam instruments because of the interaction between the hydrocarbons and the electron beam at the point of impact on the sample surface. The authors suggest that hydrocarbon contamination does affect the generated spectra and present methods for removing this (and other) time-dependent artifacts for low-voltage X-rays. The software is freely available as a compiled Windows executable and as source code (http://geoscience.wisc.edu/geoscience/?p=16417). PMID- 26555057 TI - On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development. AB - A biochemical explanation of development from the fertilized egg to the adult requires an understanding of the proteins and RNAs expressed over time during embryogenesis. We present a comprehensive characterization of protein and mRNA dynamics across early development in Xenopus. Surprisingly, we find that most protein levels change little and duplicated genes are expressed similarly. While the correlation between protein and mRNA levels is poor, a mass action kinetics model parameterized using protein synthesis and degradation rates regresses protein dynamics to RNA dynamics, corrected for initial protein concentration. This study provides detailed data for absolute levels of ~10,000 proteins and ~28,000 transcripts via a convenient web portal, a rich resource for developmental biologists. It underscores the lasting impact of maternal dowry, finds surprisingly few cases where degradation alone drives a change in protein level, and highlights the importance of transcription in shaping the dynamics of the embryonic proteome. PMID- 26555056 TI - Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis. AB - Naive pluripotency is manifest in the preimplantation mammalian embryo. Here we determine transcriptome dynamics of mouse development from the eight-cell stage to postimplantation using lineage-specific RNA sequencing. This method combines high sensitivity and reporter-based fate assignment to acquire the full spectrum of gene expression from discrete embryonic cell types. We define expression modules indicative of developmental state and temporal regulatory patterns marking the establishment and dissolution of naive pluripotency in vivo. Analysis of embryonic stem cells and diapaused embryos reveals near-complete conservation of the core transcriptional circuitry operative in the preimplantation epiblast. Comparison to inner cell masses of marmoset primate blastocysts identifies a similar complement of pluripotency factors but use of alternative signaling pathways. Embryo culture experiments further indicate that marmoset embryos utilize WNT signaling during early lineage segregation, unlike rodents. These findings support a conserved transcription factor foundation for naive pluripotency while revealing species-specific regulatory features of lineage segregation. PMID- 26555060 TI - A case of syphilitic anal condylomata lata mimicking malignancy. AB - INTRODUCTION: Condylata lata in secondary syphilis is well known presentation and needs to be considered in differential diagnosis of perianal lesions. In England between 2013 and 2014 the overall incidence of infectious syphilis increased by 33% and is mainly seen in men who have sex with men. PRESENTATION OF CASE: We report the management of a 49-years-old Caucasian homosexual man with perianal lesions that were suspicious of malignancy. After biopsies, colonoscopy, staging with computed tomography, magnetic resonance imaging and syphilis serology anal cancer was excluded and a diagnosis of syphilis was confirmed. He was referred to the sexual health clinic for the appropriate investigations and treatment. DISCUSSION: This case highlights the consideration of treatable infectious syphilis pathology. The main differential diagnosis of perianal growths to consider is condylomata acuminata (warts caused by human papillomavirus), anal cancer, syphilis, chancroid, haemorrhoids, tuberculosis and lymphogranuloma venereum. To differentiate a biopsy is needed for histopathological examination. A dense plasma cell infiltrate and numerous spirochetes visualised by immunostaining confirms condylomata lata. CONCLUSION: In UK, it is important for colorectal surgeons to be aware of syphilitic condylomata lata and consider this when dealing with perianal lesions. It is advisable to refer patients suspected of or diagnosed with syphilis to sexual health clinics to help improve outcome. In sexual health clinics additional investigations and treatment are available in addition to partner notification and follow-up can be offered. PMID- 26555059 TI - Impact of area under the concentration-time curve to minimum inhibitory concentration ratio on vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteraemia. AB - There have been few clinical studies on the association between the vancomycin 24 h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin resistant Staphylococcus aureus (MRSA) infections. To examine this association and to establish a suitable cut-off value for AUC24/MIC, a multicentre prospective observational study was conducted in patients with MRSA bacteraemia. Data were collected on all patients aged >=18 years with MRSA bacteraemia treated with vancomycin for >=72 h without dialysis. The MIC was determined by broth microdilution (BMD) and Etest. Treatment failure was defined as (i) 30-day mortality, (ii) persistent bacteraemia (>=7 days) and (iii) recurrence (<=30 days after completion of therapy). AUC24 was estimated by a Bayesian approach based on individual vancomycin concentrations. The AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by Classification and Regression Tree (CART) analysis. In total, 117 patients were enrolled, among which vancomycin treatment failure occurred in 38 (32.5%). In univariate analysis, high vancomycin MIC and low trough levels were unrelated to treatment outcomes. In the CART analysis, low vancomycin AUC24/MIC [<392.7 (BMD) and <397.2 (Etest)] was associated with treatment failure. In multivariate analysis, low AUC24/MIC was a risk factor for treatment failure [adjusted odds ratio (aOR)=3.50, 95% confidence interval (CI) 1.39-8.82 by BMD; aOR=5.61, 95% CI 2.07 15.24 by Etest]. AUC24/MIC is associated with vancomycin treatment outcomes in MRSA bacteraemia, and seeking individualised AUC24/MIC ratios above target (>400) may improve treatment outcomes. PMID- 26555061 TI - Dermoid cyst of the pancreas: A rare cystic neoplasm. AB - INTRODUCTION: Dermoid cyst of the pancreas, also called cystic teratoma, is a benign, well-differentiated, and extremely rare germ cell neoplasm. Preoperative diagnosis is challenging since there are no definitive preoperative diagnostic tests or pathognomonic findings. PRESENTATION OF CASE: We report a case of a 54 year-old male who presented with an incidentally detected pancreatic cystic mass at the tail of the pancreas. Computerized tomography revealed a benign cystic mass such as oligocystic serous cystadenoma or a hemorrhagic cyst. However, a high CEA level from EUS guided aspirated fluid suggested mucinous cystic neoplasm. After laparoscopic spleen-preserving distal pancreatectomy, the final diagnosis was confirmed as a dermoid cyst of the pancreas. CONCLUSION: Despite the benign nature of the dermoid cyst, complete surgical resection is mostly inevitable due to the difficulty of preoperative diagnosis as in the present case. PMID- 26555062 TI - Surgical management of Stenson's duct injury by using double J stent urethral catheter. AB - BACKGROUND: Parotid duct or gland injury can be caused by assault with a knife, bottle, electrical-saw, road traffic accident, or rarely gunshot and fractures of the facial skeleton. The injury can be in the form of laceration, ductal exposure, total cutting, or crushing of the duct. These conditions are difficult to diagnose because of complex anatomy and variable forms of the injury. A successful management of parotid duct injuries depends on early diagnosis and appropriate intervention; improper surgery may lead to complications such as sialocele or salivary fistula CASE REPORT: A 27-years-old man was presented to the maxillofacial unit, complaining of bleeding over the right side of his face after accidental exposure to a chain-saw three hours before admission. On examination, a 6cm deep lacerated wound was found over the right buccal area, suspecting facial nerve-buccal branch and parotid duct injury. Under general anesthesia the parotid duct injury diagnosed, microsurgical anastomosis of the cut-ends of the parotid duct performed using the double J catheter. Sutures and JJ stent removed seven and twenty postoperative days respectively. After a proper supportive treatment a complete healing of the duct was obtained with normal amount of saliva. CONCLUSIONS: Herein, we described an easy yet efficient technique in management of parotid duct injury using a JJ stent which is often used for urethra. We think that use of JJ stent is a valuable technique to be used in the diagnosis and surgical repair of the parotid duct during traumatic facial and/or parotid injuries. PMID- 26555063 TI - Expanding availability of safe abortion services through private sector accreditation: a case study of the Yukti Yojana program in Bihar, India. AB - BACKGROUND: Recognizing the need to increase access to safe abortion services to reduce maternal mortality and morbidity, the state government of Bihar, India introduced an innovative mechanism of accrediting private health care facilities. The program, Yukti Yojana ('a scheme for solution'), accredits eligible health facilities and supports them in providing abortion-related services free of charge to rural and low-income urban women. This paper describes implementation of Yukti Yojana. METHODS: A descriptive analysis of abortion services provided under the Yukti Yojana program was conducted using four data sources: 1) assessment of accredited facilities over 6 months; 2) induced and incomplete abortion service registers; 3) client exit interviews and associated direct observation of client-provider interaction for a sample of accredited facilities; and 4) in-depth interviews with providers and key stakeholders responsible for providing or influencing abortion services. These analyses assessed characteristics of women receiving abortion services, quality of care and client satisfaction, and barriers and facilitating factors of a successful accreditation process. RESULTS: Forty-nine private facilities were accredited during the first two years of the program, and 84 % had begun providing abortion services, in all 27,724 women were served. Overall, 53 % of beneficiaries reported holding a "Below Poverty Line" card, while 71 % had low living standard. The majority of women (n = 569) reported satisfaction (90 %) with their care, while 68 % perceived good quality of services. Having a government-led initiative was considered a key element of success, while stringent requirements for site approval, long waiting time for accreditation, complicated and delayed reimbursement process and low reimbursement fees for abortion services were identified as barriers to implementation. CONCLUSIONS: Yukti Yojana provides a model for successfully involving private OB/GYNs and general physicians to deliver safe abortion services to poor women on a large scale and offers additional evidence that public-private partnerships can be used to ensure availability of high-quality maternal health services to women in low-income countries. Private facility accreditation also offers a promising solution to the limited availability of safe abortion services in low resource settings such as Bihar, India. PMID- 26555064 TI - Hepatitis C, disease and its management: a cost-effectiveness analysis of the new generation oral protease inhibitors. AB - BACKGROUND: Hepatitis C, caused by a single-stranded RNA virus, has become a global health problem. Infecting millions of individuals in the United States alone, chronic HCV infection can lead to devastating medical problems including cirrhosis and hepatocellular carcinoma. These problems create millions of dollars in health-care costs for treatment and management. This study determines the cost effectiveness of hepatitis C treatment with the new generation of oral protease inhibitors. METHODS: A Markov model was constructed to simulate the progression of genotype-1 chronic hepatitis C disease in a cohort of 50-year-old patients. A decision tree, along with the Markov model, was then used to determine duration of disease, treatment success, progression of disease and mortality. At the end of each stage in the model, the cost and quality-adjusted life years (QALY) were summed for each individual. These were then used to calculate the overall cost effectiveness ratio (CER) using QALY as the unit of effectiveness. Four treatment options were modelled: sofosbuvir with pegylated interferon-alpha and ribavirin (SOF/PEG-IFN+RBV), sofosbuvir with ribavirin (SOF/RBV), simeprevir with pegylated interferon-alpha and ribavirin (SMV/PEG-IFN+RBV) and simeprevir with sofosbuvir (SMV/SOF). RESULTS: SOF/PEG-IFN+RBV yielded a CER ratio of $6,796.22/QALY, SMV/PEG-IFN+RBV of $7,642.60/QALY and SMV/SOF of $8,959.11/QALY. SOF/RBV had a higher CER of $16,295.30/QALY. It is important to note however that SMV/SOF had the highest QALY at 19.08. CONCLUSIONS: After consideration of quality of life, treatment regimens and treatment side effects, the SMV/SOF regimen yields acceptable cost-effectiveness ratios with high QALY. PMID- 26555065 TI - Sex-biased severity of sarcoptic mange at the same biological cost in a sexually dimorphic ungulate. AB - BACKGROUND: In sexually dimorphic species, male susceptibility to parasite infection and mortality is frequently higher than in females. The Iberian ibex (Capra pyrenaica) is a sexually dimorphic mountain ungulate endemic to the Iberian Peninsula commonly affected by sarcoptic mange, a chronic catabolic skin disease caused by Sarcoptes scabiei. Since 1992, sarcoptic mange affects the Iberian ibex population of the Sierra Nevada Natural Space (SNNS). This study aims at exploring whether mange severity, in terms of prevalence and its effects on body condition, is male-biased in Iberian ibex. FINDINGS: One thousand and seventy-one adult Iberian ibexes (439 females and 632 males) were randomly shot harvested in the SNNS from May 1995 to February 2008. Sarcoptic mange stage was classified as healthy, mildly infected or severely infected. Sex-biased prevalence of severe mange was evaluated by a Chi-square test whereas the interaction between mange severity and sex on body condition was assessed by additive models. Among scabietic individuals, the prevalence of severely affected males was 1.29 times higher than in females. On the other hand, both sexes were not able to take profit of a higher availability of seasonal food resources when sarcoptic, particularly in the severe stages. CONCLUSIONS: Sarcoptic mange severity is male-biased in Iberian ibex, though not mange effects on body condition. Behavioural, immunological and physiological characteristics of males may contribute to this partial sex-biased susceptibility to sarcoptic mange. PMID- 26555066 TI - pi-Topology and spin alignment in the photo-excited states of phenylanthracene-t butylnitroxide radicals. AB - We have studied the relationship between the pi-topology and the photo-excited high-spin states of pi-conjugated spin systems, 9-anthracen-(3-phenyl-t butylnitroxide) radical (1m) and 9-anthracen-(4-phenyl-t-butylnitroxide) radical (1p) systems, by time-resolved ESR and transient absorption spectroscopies. For the meta-isomer, 1m, the excited quartet high-spin state (S = 3/2) was observed, while for the para-isomer, 1p, only a weak signal of the doublet state (S = 1/2) was detected. For the quartet state of 1m, the g value and fine-structure parameters have been determined to be g = 2.005, D = 0.0250 cm(-1), and E = ~0.0 cm(-1). The mechanism of intramolecular spin alignment and the role of spin polarization in the excited states have been discussed based on the spin density distribution calculated by ab initio molecular orbital calculations. PMID- 26555067 TI - Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema: An Attempt of Composite Grading of Macular Edema. AB - PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12 month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value. PMID- 26555068 TI - Field Evaluation of Malaria Microscopy, Rapid Malaria Tests and Loop-Mediated Isothermal Amplification in a Rural Hospital in South Western Ethiopia. AB - BACKGROUND: In up to one third of the hospitals in some rural areas of Africa, laboratory services in malaria diagnosis are limited to microscopy by thin film, as no capability to perform thick film exists (gold standard in terms of sensitivity for malaria diagnosis). A new rapid molecular malaria diagnostic test called Loop-mediated isothermal DNA amplification (LAMP) has been recently validated in clinical trials showing exceptional sensitivity and specificity features. It could be a reliable diagnostic tool to be implemented without special equipment or training. OBJECTIVE: The objective of this proof of concept study was to confirm the feasibility of using LAMP technique for diagnosis of malaria in a rural Ethiopian hospital with limited resources. METHODOLOGY/PRINCIPAL FINDINGS: This study was carried out in Gambo General Hospital, West Arsi Province (Ethiopia), from November 1st to December 31st 2013. A total of 162 patients with a non-focal febrile syndrome were investigated. The diagnostic capability (sensitivity, specificity, positive predictive and negative predictive values) of rapid malaria tests and microscopy by thin film was evaluated in comparison with LAMP. Eleven (6.79%) out of the 162 patients with fever and suspected malaria, tested positive for LAMP, 3 (1.85%) for rapid malaria tests and none of the eleven cases was detected by thin film microscopy. CONCLUSIONS/SIGNIFICANCE: LAMP can be performed in basic rural laboratories without the need for specialized infrastructure and it may set a reliable tool for malaria control to detect a low level parasitemia. PMID- 26555070 TI - Parasitological, Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa) in the Baboon (Papio anubis). AB - BACKGROUND: Loiasis, a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae (mf) following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation. METHODOLOGY/PRINCIPLE FINDINGS: Fifteen baboons (Papio anubis) were infected with 600 infective larvae (L3) isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1-2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4-8 months, with a majority (60%) of animals becoming patent by 5 months post infection (MPI); all animals were patent by 8 MPI. Microfilarial loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000 mf/mL with 50% of these animals with mf >50,000 mf/mL. Absolute eosinophil, creatinine, Ca2+ and K+ levels were generally above normal values (NV). Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca2+, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels. CONCLUSIONS: Infection of splenectomised baboons with L. loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans. PMID- 26555071 TI - Modeling Soil Organic Carbon at Regional Scale by Combining Multi-Spectral Images with Laboratory Spectra. AB - There is a great challenge in combining soil proximal spectra and remote sensing spectra to improve the accuracy of soil organic carbon (SOC) models. This is primarily because mixing of spectral data from different sources and technologies to improve soil models is still in its infancy. The first objective of this study was to integrate information of SOC derived from visible near-infrared reflectance (Vis-NIR) spectra in the laboratory with remote sensing (RS) images to improve predictions of topsoil SOC in the Skjern river catchment, Denmark. The second objective was to improve SOC prediction results by separately modeling uplands and wetlands. A total of 328 topsoil samples were collected and analyzed for SOC. Satellite Pour l'Observation de la Terre (SPOT5), Landsat Data Continuity Mission (Landsat 8) images, laboratory Vis-NIR and other ancillary environmental data including terrain parameters and soil maps were compiled to predict topsoil SOC using Cubist regression and Bayesian kriging. The results showed that the model developed from RS data, ancillary environmental data and laboratory spectral data yielded a lower root mean square error (RMSE) (2.8%) and higher R2 (0.59) than the model developed from only RS data and ancillary environmental data (RMSE: 3.6%, R2: 0.46). Plant-available water (PAW) was the most important predictor for all the models because of its close relationship with soil organic matter content. Moreover, vegetation indices, such as the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were very important predictors in SOC spatial models. Furthermore, the 'upland model' was able to more accurately predict SOC compared with the 'upland & wetland model'. However, the separately calibrated 'upland and wetland model' did not improve the prediction accuracy for wetland sites, since it was not possible to adequately discriminate the vegetation in the RS summer images. We conclude that laboratory Vis-NIR spectroscopy adds critical information that significantly improves the prediction accuracy of SOC compared to using RS data alone. We recommend the incorporation of laboratory spectra with RS data and other environmental data to improve soil spatial modeling and digital soil mapping (DSM). PMID- 26555069 TI - Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. AB - OBJECTIVE: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). DESIGN: 24-week randomized open-label prospective evaluation. METHOD: Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls. RESULTS: At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group. CONCLUSIONS: A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. PMID- 26555072 TI - Depth-of-Focus Correction in Single-Molecule Data Allows Analysis of 3D Diffusion of the Glucocorticoid Receptor in the Nucleus. AB - Single-molecule imaging of proteins in a 2D environment like membranes has been frequently used to extract diffusive properties of multiple fractions of receptors. In a 3D environment the apparent fractions however change with observation time due to the movements of molecules out of the depth-of-field of the microscope. Here we developed a mathematical framework that allowed us to correct for the change in fraction size due to the limited detection volume in 3D single-molecule imaging. We applied our findings on the mobility of activated glucocorticoid receptors in the cell nucleus, and found a freely diffusing fraction of 0.49+/-0.02. Our analysis further showed that interchange between this mobile fraction and an immobile fraction does not occur on time scales shorter than 150 ms. PMID- 26555073 TI - Network Physiology: How Organ Systems Dynamically Interact. AB - We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems. PMID- 26555074 TI - Landscape Diversity and Crop Vigor Influence Biological Control of the Western Grape Leafhopper (E. elegantula Osborn) in Vineyards. AB - This study evaluated how the proportional area of natural habitat surrounding a vineyard (i.e. landscape diversity) worked in conjunction with crop vigor, cultivar and rootstock selection to influence biological control of the western grape leafhopper (Erythroneura elegantula Osborn). The key natural enemies of E. elegantula are Anagrus erythroneurae S. Trjapitzin & Chiappini and A. daanei Triapitsyn, both of which are likely impacted by changes in landscape diversity due to their reliance on non-crop habitat to successfully overwinter. Additionally, E. elegantula is sensitive to changes in host plant quality which may influence densities on specific cultivars, rootstocks and/or vines with increased vigor. From 2010-2013, data were collected on natural enemy and leafhopper densities, pest parasitism rates and vine vigor from multiple vineyards that represented a continuum of landscape diversity. Early in the season, vineyards in more diverse landscapes had higher Anagrus spp. densities and lower E. elegantula densities, which led to increased parasitism of E. elegantula. Although late season densities of E. elegantula tended to be lower in vineyards with higher early season parasitism rates and lower total petiole nitrogen content, they were also affected by rootstock and cultivar. While diverse landscapes can support higher natural enemy populations, which can lead to increased biological control, leafhopper densities also appear to be mediated by cultivar, rootstock and vine vigor. PMID- 26555075 TI - The Retinoblastoma Tumor Suppressor Transcriptionally Represses Pak1 in Osteoblasts. AB - We previously characterized the retinoblastoma tumor suppressor protein (Rb) as a regulator of adherens junction assembly and cell-to-cell adhesion in osteoblasts. This is a novel function since Rb is predominantly known as a cell cycle repressor. Herein, we characterized the molecular mechanisms by which Rb performs this function, hypothesizing that Rb controls the activity of known regulators of adherens junction assembly. We found that Rb represses the expression of the p21 activated protein kinase (Pak1), an effector of the small Rho GTPase Rac1. Rac1 is a well-known regulator of adherens junction assembly whose increased activity in cancer is linked to perturbations of intercellular adhesion. Using nuclear run on and luciferase reporter transcription assays, we found that Pak1 repression by Rb is transcriptional, without affecting Pak1 mRNA and protein stability. Pak1 promoter bioinformatics showed multiple E2F1 binding sites within 155 base pairs of the transcriptional start site, and a Pak1-promoter region containing these E2F sites is susceptible to transcriptional inhibition by Rb. Chromatin immunoprecipitations showed that an Rb-E2F complex binds to the region of the Pak1 promoter containing the E2F1 binding sites, suggesting that Pak1 is an E2F target and that the repressive effect of Rb on Pak1 involves blocking the trans activating capacity of E2F. A bioinformatics analysis showed elevated Pak1 expression in several solid tumors relative to adjacent normal tissue, with both Pak1 and E2F increased relative to normal tissue in breast cancer, supporting a cancer etiology for Pak1 up-regulation. Therefore, we propose that by repressing Pak1 expression, Rb prevents Rac1 hyperactivity usually associated with cancer and related to cytoskeletal derangements that disrupt cell adhesion, consequently enhancing cancer cell migratory capacity. This de-regulation of cell adhesion due to Rb loss could be part of the molecular events associated with cancer progression and metastasis. PMID- 26555076 TI - Complete Genomic and Lysis-Cassette Characterization of the Novel Phage, KBNP1315, which Infects Avian Pathogenic Escherichia coli (APEC). AB - Avian pathogenic Escherichia coli (APEC) is a major pathogen that causes avian colibacillosis and is associated with severe economic losses in the chicken farming industry. Here, bacteriophage KBNP1315, infecting APEC strain KBP1315, was genomically and functionally characterized. The evolutionary relationships of KBNP1315 were analyzed at the genomic level using gene (protein)-sharing networks, the Markov clustering (MCL) algorithm, and comparative genomics. Our network analysis showed that KBNP1315 was connected to 30 members of the Autographivirinae subfamily, which comprises the SP6-, T7-, P60-, phiKMV-, GAP227 and KP34-related groups. Network decomposition suggested that KBNP1315 belongs to the SP6-like phages, but our comparison of putative encoded proteins revealed that key proteins of KBNP1315, including the tail spike protein and endolysin, had relative low levels of amino acid sequence similarity with other members of the SP6-like phages. Thus KBNP1315 may only be distantly related to the SP6-like phages, and (based on the difference in endolysin) its lysis mechanism may differ from theirs. To characterize the lytic functions of the holin and endolysin proteins from KBNP1315, we expressed these proteins individually or simultaneously in E. coli BL21 (DE3) competent cell. Interestingly, the expressed endolysin was secreted into the periplasm and caused a high degree of host cell lysis that was dose-dependently delayed/blocked by NaN3-mediated inhibition of the SecA pathway. The expressed holin triggered only a moderate inhibition of cell growth, whereas coexpression of holin and endolysin enhanced the lytic effect of endolysin. Together, these results revealed that KBNP1315 appears to use a pin-holin/signal-arrest-release (SAR) endolysin pathway to trigger host cell lysis. PMID- 26555077 TI - Do Patients Want to Die at Home? A Systematic Review of the UK Literature, Focused on Missing Preferences for Place of Death. AB - BACKGROUND: End-of-life care policy has a focus on enabling patients to die in their preferred place; this is believed for most to be home. This review assesses patient preferences for place of death examining: the extent of unreported preferences, the importance of patient factors (place of care and health diagnosis) and who reports preferences. METHODS AND FINDINGS: Systematic literature review of 7 electronic databases, grey literature, backwards citations from included studies and Palliative Medicine hand search. Included studies published between 2000-2015, reporting original, quantifiable results of adult UK preferences for place of death. Of 10826 articles reviewed, 61 met the inclusion criteria. Summary charts present preferences for place of death by health diagnosis, where patients were asked and who reported the preference. These charts are recalculated to include 'missing data,' the views of those whose preferences were not asked, expressed or reported or absent in studies. Missing data were common. Across all health conditions when missing data were excluded the majority preference was for home: when missing data were included, it was not known what proportion of patients with cancer, non-cancer or multiple conditions preferred home. Patients, family proxies and public all expressed a majority preference for home when missing data were excluded: when included, it was not known what proportion of patients or family proxies preferred home. Where patients wished to die was related to where they were asked their preference. Missing data calculations are limited to 'reported' data. CONCLUSIONS: It is unknown what proportion of patients prefers to die at home or elsewhere. Reported preferences for place of death often exclude the views of those with no preference or not asked: when 'missing data' are included, they supress the proportion of preferences for all locations. Caution should be exercised if asserting that most patients prefer to die at home. PMID- 26555078 TI - Human papillomavirus and its clinical relevance in oesophageal squamous cell carcinoma in a Kurdish population in the west of Iran. AB - Background The aetiological role of Human Papillomavirus (HPV) in oesophageal squamous cell carcinoma (ESCC) was evaluated by assessment of the presence and status of HPV DNA in a Kurdish population in the west of Iran. Methods One hundred and three paraffin-embedded ESCC tissue samples, diagnosed between 2007 2013, were included in the study. DNA was extracted and then HPV presence and genotypes were determined by PCR and INNO-LiPA genotyping, respectively. Results HPV DNA was detected in 11/103 (10.7%) of ESCCs. HPV-18 and HPV-16 genotypes were determined in five and six samples, respectively. Co-infection of HPV-6 was only found with HPV-18 in two cases. There were no statistically significant distinctions between HPV-positive and HPV-negative cases with regard to clinical and pathologic findings. Conclusion The present study indicates that, among a group of Kurdish people in two provinces in the west of Iran, as a low-risk ESCC area, HPV could be one of the risk factors, although in a small proportion of the patients. PMID- 26555079 TI - Anxiety, attention, and decision making: The moderating role of heart rate variability. AB - The current exploratory research examined whether high frequency heart rate variability (HF-HRV) modulates the association between anxiety and (1) executive attentional control during situations involving neutral stimuli, in which the distractor stimuli are in conflict with the target stimulus, and (2) risk aversion in decision making. Forty-five participants (21 with low and 24 with high trait-anxiety) performed a modified version of the Attention Network Test to measure attentional control, and the Balloon Analog Risk Task to measure risk aversion. HF-HRV was recorded during a rest period before completion of the tasks. Results showed that individuals with high anxiety and low HF-HRV have worse attentional control in the face of conflicting information as well as greater risk aversion, in comparison with individuals with both high anxiety and high HF-HRV or low anxiety (regardless of HF-HRV). HF-HRV was positively associated with attentional control and negatively associated with risk aversion. Furthermore, a strong negative association was observed between attentional control and risk aversion. These results suggest that HF-HRV modulates the influence of anxiety on both attentional control to neutral stimuli, and risk aversion in decision making. Greater HF-HRV appears to fulfill a protective role in highly anxious individuals. The associations observed also suggest that executive control of attention plays a relevant role in decision making. These results support the relevance of the autonomic nervous system in sustained cognition and are in accordance with theories in which vagal-mediated heart rate variability is taken as an indicator of prefrontal cortex inhibitory influences. PMID- 26555080 TI - Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD. AB - BACKGROUND AND OBJECTIVES: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare pediatric disease of unknown cause. Here, in response to a recent case report describing a ROHHAD patient who suffered from secondary narcolepsy confirmed by an absence of hypocretin-1 in the cerebrospinal fluid, we consider whether the ROHHAD phenotype is owing to one or more mutations in genes specific to hypocretin protein signalling. METHODS: DNA samples from 16 ROHHAD patients were analyzed using a combination of next-generation and Sanger sequencing to identify exonic sequence variations in three genes: HCRT, HCRTR1, and HCRTR2. RESULTS: No rare or novel mutations were identified in the exons of HCRT, HCRTR1, or HCRTR2 genes in a set of 16 ROHHAD patients. CONCLUSIONS: ROHHAD is highly unlikely to be caused by mutations in the exons of the genes for hypocretin and its two receptors. PMID- 26555081 TI - Effect of lung resection on pleuro-pulmonary mechanics and fluid balance. AB - The aim of the study was to determine in human patients the effect of lung resection on lung compliance and on pleuro-pulmonary fluid balance. Pre and post operative values of compliance were measured in anesthetized patients undergoing resection for lung cancer (N=11) through double-lumen bronchial intubation. Lung compliance was measured for 10-12 cm H2O increase in alveolar pressure from 5 cm H2O PEEP in control and repeated after resection. No air leak was assessed and pleural fluid was collected during hospital stay. A significant negative correlation (r(2)=0.68) was found between compliance at 10 min and resected mass. Based on the pre-operative estimated lung weight, the decrease in compliance following lung resection exceeded by 10-15% that expected from resected mass. Significant negative relationships were found by relating pleural fluid drainage flow to the remaining lung mass and to post-operative lung compliance. Following lung re-expansion, data suggest a causative relationship between the decrease in compliance and the perturbation in pleuro-pulmonary fluid balance. PMID- 26555083 TI - Breast metastasis from melanoma mimicking inflammatory breast cancer. PMID- 26555085 TI - Maximum rates of climate change are systematically underestimated in the geological record. AB - Recently observed rates of environmental change are typically much higher than those inferred for the geological past. At the same time, the magnitudes of ancient changes were often substantially greater than those established in recent history. The most pertinent disparity, however, between recent and geological rates is the timespan over which the rates are measured, which typically differ by several orders of magnitude. Here we show that rates of marked temperature changes inferred from proxy data in Earth history scale with measurement timespan as an approximate power law across nearly six orders of magnitude (10(2) to >10(7) years). This scaling reveals how climate signals measured in the geological record alias transient variability, even during the most pronounced climatic perturbations of the Phanerozoic. Our findings indicate that the true attainable pace of climate change on timescales of greatest societal relevance is underestimated in geological archives. PMID- 26555084 TI - Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non anesthetized Recordings. AB - The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli such as endotoxins, bacteria, umbilical cord occlusions, hypoxia and various pharmacological treatments. The life-saving clinical practices of glucocorticoid treatment in fetuses at risk of premature birth and the therapeutic hypothermia have been developed in this model. This is due to the unique amenability of the non anesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation and in vivo organ imaging. Here we describe the surgical instrumentation procedure required to achieve a stable chronically instrumented non-anesthetized fetal sheep model including characterization of the post-operative recovery from blood gas, metabolic and inflammation standpoints. PMID- 26555086 TI - Analytical ultracentrifugation: A versatile tool for the characterisation of macromolecular complexes in solution. AB - Analytical ultracentrifugation, an early technique developed for characterizing quantitatively the solution properties of macromolecules, remains a powerful aid to structural biologists in their quest to understand the formation of biologically important protein complexes at the molecular level. Treatment of the basic tenets of the sedimentation velocity and sedimentation equilibrium variants of analytical ultracentrifugation is followed by considerations of the roles that it, in conjunction with other physicochemical procedures, has played in resolving problems encountered in the delineation of complex formation for three biological systems - the cytoplasmic dynein complex, mitogen-activated protein kinase (ERK2) self-interaction, and the terminal catalytic complex in selenocysteine synthesis. PMID- 26555087 TI - USP10 Expression in Normal Adrenal Gland and Various Adrenal Tumors. AB - Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, is associated with androgen receptor transcriptional activity and pathological processes of tumor. However, information between USP10 and the adrenal gland is limited. In particular, the role of USP10 in adrenal tumors has not been elucidated yet. This study aims to investigate the expression of USP10 in the human normal adrenal gland and various adrenal tumors. Tissue samples were obtained from 30 adrenocortical adenomas, nine adrenocortical adenocarcinomas, and 20 pheochromocytomas following laparoscopic surgery. Twenty normal adrenal glands were obtained from kidney surgical resection conducted due to renal cell carcinomas. USP10 expression was investigated on protein levels using immunohistochemistry and on mRNA levels using bioinformatics analysis in the Gene Expression Omnibus (GEO) Datasets. In the 20 cases of normal adrenal glands analyzed, USP10 protein was constantly expressed in situ in the cortex of the adrenal glands, but in the medulla of the gland, only the sustentacular cells were detected positive. In adrenal tumors, detectable levels of USP10 protein were found in 100 % (30/30) adrenocortical adenomas, 88.89 % (8/9) adrenocortical carcinomas, and 10 % (2/20) pheochromocytomas. Bioinformatics analysis did not show a significant difference in USP10 messenger RNA (mRNA) expression between adrenal tumors and normal adrenal gland tissues. A positive USP10 immunoreaction can be useful in distinguishing adrenal cortical tumors from pheochromocytoma. PMID- 26555088 TI - Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease. AB - The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6 hydroxydopmaine (6-OHDA, 20 MUg/4 MUl) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1beta and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-OHDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BBB associated with the disease. PMID- 26555089 TI - A Systematic Review of Loneliness and Smoking: Small Effects, Big Implications. AB - BACKGROUND: Research supports an association between smoking and negative affect. Loneliness is a negative affective state experienced when a person perceives themselves as socially isolated and is associated with poor health behaviors and increased morbidity and early mortality. OBJECTIVES: In this article, we systematically review the literature on loneliness and smoking and suggest potential theoretical and methodological implications. METHODS: PubMed and PsycINFO were systematically searched for articles that assessed the statistical association between loneliness and smoking. Articles that met study inclusion criteria were reviewed. RESULTS: Twenty-five studies met inclusion criteria. Ten studies were conducted with nationally representative samples. Twelve studies assessed loneliness using a version of the UCLA Loneliness Scale and nine used a one-item measure of loneliness. Seventeen studies assessed smoking with a binary smoking status variable. Fourteen of the studies were conducted with adults and 11 with adolescents. Half of the reviewed studies reported a statistically significant association between loneliness and smoking. Of the studies with significant results, all but one study found that higher loneliness scores were associated with being a smoker. CONCLUSIONS/IMPORTANCE: Loneliness and smoking are likely associated, however, half of the studies reviewed did not report significant associations. Studies conducted with larger sample sizes, such as those that used nationally representative samples, were more likely to have statistically significant findings. Future studies should focus on using large, longitudinal cohorts, using measures that capture different aspects of loneliness and smoking, and exploring mediators and moderators of the association between loneliness and smoking. PMID- 26555090 TI - New insight into the phosphorylation-regulated intranuclear localization of human cytomegalovirus pUL69 mediated by cyclin-dependent kinases (CDKs) and viral CDK orthologue pUL97. AB - Cyclin-dependent kinases (CDKs) are multifaceted regulators involved in the replication of human cytomegalovirus. Recently, we demonstrated an interaction of CDK9-cyclin T1 as well as viral CDK orthologue pUL97 with the viral regulator pUL69, thereby leading to pUL69-activating phosphorylation. Here, we demonstrate that colocalization and direct pUL69-cyclin T1 interaction is independent of viral strains and host cell types. In vitro phosphorylation of pUL69 by CDK9 or pUL97 did not occur in a single site-specific manner, but at multiple sites. The previously described fine-speckled nuclear aggregation of pUL69 was assigned to the late phase of viral replication. CDK inhibitors, including a novel inhibitor of the CDK-activating kinase CDK7, massively intensified this fine-speckled accumulation. Interestingly, we also observed spontaneous pUL69 accumulation in the absence of inhibitors at a lower frequency. These findings provide new insight into pUL69 kinase interregulation and emphasize the importance of pUL69 phosphorylation for correct intranuclear localization. PMID- 26555092 TI - Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case. AB - BACKGROUND: Approximately 10-15 % of gastrointestinal stromal tumors (GISTs) lack gain of function mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. An alternate mechanism of oncogenesis through loss of function of the succinate-dehydrogenase (SDH) enzyme complex has been identified for a subset of these "wild type" GISTs. METHODS: Paired tumor and normal DNA from an SDH-intact wild-type GIST case was subjected to whole exome sequencing to identify the pathogenic mechanism(s) in this tumor. Selected findings were further investigated in panels of GIST tumors through Sanger DNA sequencing, quantitative real-time PCR, and immunohistochemical approaches. RESULTS: A hemizygous frameshift mutation (p.His2261Leufs*4), in the neurofibromin 1 (NF1) gene was identified in the patient's GIST; however, no germline NF1 mutation was found. A somatic frameshift mutation (p.Lys54Argfs*31) in the MYC associated factor X (MAX) gene was also identified. Immunohistochemical analysis for MAX on a large panel of GISTs identified loss of MAX expression in the MAX-mutated GIST and in a subset of mainly KIT-mutated tumors. CONCLUSION: This study suggests that inactivating NF1 mutations outside the context of neurofibromatosis may be the oncogenic mechanism for a subset of sporadic GIST. In addition, loss of function mutation of the MAX gene was identified for the first time in GIST, and a broader role for MAX in GIST progression was suggested. PMID- 26555082 TI - Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease? AB - PURPOSE: Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. METHODS: We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. RESULTS: In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. CONCLUSION: Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions. PMID- 26555093 TI - Characterization of mesenchymal stem cells derived from the equine synovial fluid and membrane. AB - BACKGROUND: Isolation of mesenchymal stem cells (MSCs) in equines, has been reported for different tissues including bone marrow, adipose, umbilical cord, peripheral blood, and yolk sac. In regard to the MSCs derived from synovial fluid (SF) or membrane (SM), there is data available for humans, dogs, pigs, goats and horses. Especially in equines, these cells have being considered promising candidates for articular regeneration. Herein, we established and characterized MSCs obtained from equine SF and SM. Samples were obtained during arthroscopy and cultured using MEM (Minimum Essential Medium). MSCs were characterized by morphology and expression of specific markers for stem cells, pluripotency, inflammation, and cell cycle. RESULTS: The medium MEM was more effective (97% +/- 2) to maintain both cultures. The cultures were composed by adherent cells with fibroblast-like shape, which had a growth pattern represented by a sigmoidal curve. After the expansion, the cells were analyzed by flow cytometry for stem cells, inflammatory, and cell cycle markers, and both lineages showed significant expression of CD45, Oct3/4, Nanog, CD105, CD90, CD34, CD117, CD133, TRA-1-81, VEGF, and LY6a. In contrast, there were differences in the cell cycle phases between the lineages, which was not observed in relation to the mitochondrial electrical potential. CONCLUSION: Given the large impact that joint pathology has on the athletic performance horses, our results suggested that the SF and SM are promising sources of stem cells with satisfactory characteristics of growth and gene expression that can be used in equine regenerative medicine. PMID- 26555096 TI - Controlling the prion propensity of glutamine/asparagine-rich proteins. AB - The yeast Saccharomyces cerevisiae can harbor a number of distinct prions. Most of the yeast prion proteins contain a glutamine/asparagine (Q/N) rich region that drives prion formation. Prion-like domains, defined as regions with high compositional similarity to yeast prion domains, are common in eukaryotic proteomes, and mutations in various human proteins containing prion-like domains have been linked to degenerative diseases, including amyotrophic lateral sclerosis. Here, we discuss a recent study in which we utilized two strategies to generate prion activity in non-prion Q/N-rich domains. First, we made targeted mutations in four non-prion Q/N-rich domains, replacing predicted prion inhibiting amino acids with prion-promoting amino acids. All four mutants formed foci when expressed in yeast, and two acquired bona fide prion activity. Prion activity could be generated with as few as two mutations, suggesting that many non-prion Q/N-rich proteins may be just a small number of mutations from acquiring aggregation or prion activity. Second, we created tandem repeats of short prion-prone segments, and observed length-dependent prion activity. These studies demonstrate the considerable progress that has been made in understanding the sequence basis for aggregation of prion and prion-like domains, and suggest possible mechanisms by which new prion domains could evolve. PMID- 26555098 TI - Timing of harvest of Phragmites australis (CAV.) Trin. ex Steudel affects subsequent canopy structure and nutritive value of roughage in subtropical highland. AB - In recent decades, constructed wetlands dominated by common reeds [Phragmites australis (CAV.) Trin. ex Steudel] have been utilized for treating nitrogen-rich wastewaters. Although plant harvest is a vegetation management in constructed wetlands for the purpose of improving nutrient removal, harvested biomass has become a problem in many places. The reed has attracted increasing interest for its potential as high-quality roughage for ruminants. Therefore, it is crucial to understand the effect of reed harvest timing on subsequent regrowth, reconstruction of canopy structure, and nutritive value of regrown biomass for roughage when defining an appropriate vegetation management in constructed wetlands. The shoots of common reeds were harvested in January (winter), March (spring), and May (early summer) in a free-water surface constructed wetland in southwest China. Harvesting in winter enhanced the shoot regrowth and concentrations of total digestible nutrients (TDN), probably due to vigorous translocations of nonstructural carbohydrates from rhizomes. Harvesting in spring and early summer decreased aboveground biomass, nitrogen (N) standing stock, and concentrations of TDN. From fifty to 110 days after harvest, the TDN had sharply declined to values similar to non-harvested stands. Thus, to obtain high-quality roughage, it is recommended that regrown shoots be harvested again within a year in the early growing stage after the first harvest in winter. PMID- 26555099 TI - GIS applied to agriclimatological zoning and agrotoxin residue monitoring in tomatoes: A case study in Espirito Santo state, Brazil. AB - Searches related to global warming have provided important insights into the response of terrestrial ecosystems, but few have examined the impacts on agricultural crops, particularly those associated with the monitoring of agrotoxin residues. In this context, the agriclimatological zoning is an important tool in the planning and consolidation of crops and should be considered in any initiative that involves such planning. This tool is particularly important in the analysis of agrotoxin residues and may be applied by the Program Analysis of Agrotoxin Residues in Food (PARA) created by the National Health Vigilance Agency of Brazil (ANVISA), which enables greater food security and contributes to the improvement of human health. The aim of this study was to elaborate the current and future agriclimatological zoning for the tomato crop, relating it with the monitoring of samples collected by PARA in Espirito Santo State, Brazil. The results indicate that a temperature increase of 5 degrees C creates a decrease in apt areas from 37.3% to 4.3%, for a total reduction of 33 percentage points (-88.5%). It is noted that of the 41 producing municipalities, only 26 have apt areas greater than 50%, highlighting the municipalities with apt areas greater than 90%, represented by Mantenopolis (100%), Guacui (98.5%), Sao Jose do Calcado (97.8%), Irupi (94.4%), Santa Teresa (92.3%), and Marechal Floriano (91.4%). The veracity of agriclimatological zoning is proved by a Kendall rank correlation coefficient of 0.876, indicating that the distribution of the variables of apt areas and productivity are similar at the significance level of 0.05 with a confidence interval 95%. After validation of the agriclimatological zoning for the tomato crop, it is recommended that the PARA should monitor 36 municipalities rather than the current 18, representing an increase of 100%. The methodology can be adjusted to agricultural crops of other countries. PMID- 26555100 TI - Investigating the differences between receptor and dispersion modeling for concentration prediction and health risk assessment of volatile organic compounds from petrochemical industrial complexes. AB - Receptor and dispersion models both provide important information to help understand the emissions of volatile organic compounds (VOCs) and develop effective management strategies. In this study, differences between the predicted concentrations of two models and the associated impacts on the estimated health risks due to different theories behind two models were investigated. Two petrochemical industrial complexes in Kaohsiung city of southern Taiwan were selected as the sites for this comparison. Although the study compares the approaches by applying the methods to this specific area, the results are expected to be adopted for other areas or industries. Ninety-nine VOC concentrations at eight monitoring sites were analyzed, with the effects of diurnal temperature and seasonal humidity variations being considered. The Chemical Mass Balance (CMB) receptor model was used for source apportionment, while the Industrial Source Complex (ISC) dispersion model was used to predict the VOC concentrations at receptor sites. In the results of receptor modeling, 54% +/- 11% and 49% +/- 20% of the monitored concentrations were contributed by process emissions in two complexes, whereas the numbers increased to 78% +/- 41% and 64% +/- 44% in the results of dispersion modeling. Significant differences were observed between two model predictions (p < 0.05). The receptor model was more reproducible given the smaller variances of its results. The effect of seasonal humidity variation on two model predictions was not negligible. Similar findings were observed given that the cancer and non-cancer risks estimated by the receptor model were lower but more reproducible. The adverse health risks estimated by the dispersion model exceeded and were 75.3%-132.4% of the values estimated by using the monitored data, whereas the percentages were lowered to the range from 27.4% to 53.8% when the prediction was performed by using the receptor model. As the results of different models could be significantly different and affect the final health risk assessment, it is important to carefully choose an appropriate model for prediction and to evaluate by monitoring to avoid providing false information for appropriate management. PMID- 26555101 TI - Flocculated sediments can reduce the size of sediment basin at construction sites. AB - Due to stringent water quality regulations on stormwater discharges, there is increasing interest in chemically-assisted settling of suspended sediments at construction sites. This study investigated settling characteristics of flocculated sediment by polyacrylamide (PAM) in a top-loading settling tube. Studied sediment materials were obtained from construction sites in North Carolina, USA: Coastal Plain loamy sand (CPLS), Piedmont sandy clay loam (PSCL), Piedmont silt loam (PSL), and Mountain clay loam (MCL). The four different sediment suspensions mixed with and without dissolved PAM were introduced to the top of the column individually. During a 1-h settling period, samples were taken at 1-m depth from surface at various times and analyzed for total suspended solids (TSS). Flocculated sediment by PAM greatly increased its settled TSS fraction up to 95-97% only in 1-min settling period compared to those of unflocculated sediment (16-72%). The settling improvement by PAM was profound in the finer-textured soils (PSL and MCL) by increasing their median particle settling velocity (>2 cm s(-1)) compared to unflocculated counterparts (<1.1 cm s(-1)). Estimated surface area requirement of sediment basin suggested that the basins receiving flocculated sediment could be reduced in size (surface area) by 2- to 4-times compared to those receiving unflocculated sediment. Our results suggests that current sediment basin design could be modified when chemically assisted settling is implemented, taking up less space and cost in construction sites. PMID- 26555091 TI - Human plasma protein N-glycosylation. AB - Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level. PMID- 26555102 TI - Reply. PMID- 26555103 TI - Quantification of aging effects upon global knee inflammation by 18F-FDG-PET. AB - OBJECTIVE: The goal of this study was to quantify aging effects upon the global knee joint and surrounding capsule and soft tissue inflammation using fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging. METHODS: This reanalysis of a prospective study included 64 patients who had undergone 18F-FDG-PET for evaluation of hip joint prostheses, and whose scans included the knee joints in the field of view. Mean patient age was 53 years (range: 33-84 years). A fixed sized three-dimensional region of interest was placed around each knee joint, paying close attention to exclude the popliteal vessels. 18F-FDG-avid regions in each knee joint were then segmented using an adaptive contrast-oriented thresholding method, and metabolically active volume (MAV), mean standardized uptake value (SUV mean), partial volume-corrected SUV mean (cSUV mean), and partial volume-corrected mean metabolic volumetric product (cMVP mean = cSUV mean * MAV) of the segmented regions were calculated. Finally, global knee inflammation (GKI) for each knee joint was calculated as the sum of cMVP mean in all segmented regions. Association of GKI with age was assessed with Pearson's correlation and linear regression methods, and GKI was compared between patients at different ages - between patients younger than 55 years and those older than 55 years - using the unpaired t-test. RESULTS: The correlation coefficient of GKI with advancing age was 0.57 (P = 0.02). In the linear regression model, considering GKI as the dependent variable and age and sex as independent covariates, the beta coefficient of age was 2.1 (95% confidence interval: 1.1 3.2). For patients aged younger than 55 years versus those aged older than 55 years, the mean GKI was 157 and 190 cm3, respectively (P = 0.01). CONCLUSION: Through the use of novel quantitative techniques, we were able to calculate GKI and demonstrate a significant increase in the entity of joint inflammation with advancing age. As degenerative disease is age-related and inflammation is implicated in its pathogenesis, our findings further support this association. These preliminary data suggest that this approach can potentially provide a means to objectively quantify the degree of inflammation in various joint disorders, and possibly in other knee degenerative/inflammatory diseases. PMID- 26555104 TI - Application of Rapid Serologic Tests for Detection of Mycobacterium bovis Infection in Free-Ranging Warthogs (Phacochoerus africanus)--Implications for Antemortem Disease Screening. AB - Warthogs (Phacochoerus africanus) have been implicated as potential maintenance hosts of Mycobacterium bovis. Our preliminary investigation of bovine tuberculosis in three warthogs describes pathologic findings and associated positive serologic results in two infected animals. This demonstrates the potential use of serodiagnostic tests for M. bovis infection in this species. PMID- 26555105 TI - Survival of Frog Virus 3 in Freshwater and Sediment from an English Lake. AB - Ranaviruses can be transmitted by contaminated water and sediment but must retain infectivity for a sufficient period to reach and infect a susceptible host. To determine the risk a virus represents once it enters the environment, its persistence in that environment must be determined. We evaluated the survival of frog virus 3 (FV3) in water and sediment from an English lake at temperatures of 4, 15, 20, and 30 C over time. The virus survived in both water and sediment; however, survival times were significantly lower in sediment. The virus lost infectivity in both matrices with a rise in temperature. In water, time required for a 90% reduction in virus titer decreased from 34 d at 4 C to 5 d at 30 C. In sediment, required time for a 90% reduction decreased from 10 d at 4 C to 1 d at 30 C. These results can be used to estimate the persistence of FV3 in the environment and indicate that the virus could remain infectious in temperate locations for extended periods during winter. PMID- 26555106 TI - Prevalence of Circulating Antibodies to Bovine Herpesvirus 1 in Yaks (Bos grunniens) on the Qinghai-Tibetan Plateau, China. AB - Bovine Herpesvirus 1 (BoHV-1) causes infections with many clinical signs, including rhinotracheitis, encephalitis, and genital lesions. The virus occurs worldwide in bovines, and in recent years, it has been reported in yaks (Bos grunniens) inhabiting the Tibetan Plateau in China. However, there is little epidemiologic data describing BoHV-1 infections in China's yak herds. We conducted a cross-sectional study on the Qinghai-Tibetan Plateau (QTP) in China July 2011-July 2012 to estimate the prevalence of BoHV-1 antibody in yak herds. We collected 1,840 serum samples from yaks on the QTP, in Tibet (988 yaks), Qinghai (475 yaks), and Sichuan (377 yaks) Provinces. Using an enzyme-linked immunosorbent assay, we found that 381 (38.6%) of the Tibetan samples, 212 (44.6%) of the Qinghai samples, and 105 (27.9%) of the Sichuan samples had detectable antibodies to BoHV-1. Given that this high prevalence of infection in yaks could result in heavy economic losses, we suggest that an effective management program, including vaccination and strategies for infection control, be developed. PMID- 26555107 TI - Polymelia and Syndactyly in a Swainson's Hawk (Buteo swainsoni). AB - A hatch-year Swainson's Hawk (Buteo swainsoni) recovered from Modoc County, California, US, on 12 August 2012 had malformations of the rear limbs consisting of bilateral polymelia and syndactyly. We describe the malformations and evaluate potential causes. Postmortem examination revealed varus rotation of both femurs and abnormal appendages originating from the distal medial surface of the tibiotarsi with two nonfunctional digits on the right leg and one digit on the left leg. There was syndactyly between digits III and IV of both feet. Avian pox viral dermatitis was present on the skin of the ventral abdomen. A definitive cause of the skeletal malformations was not identified. PMID- 26555108 TI - Shot Ingestion by Wintering Female Northern Pintails (Anas acuta) in the Texas Coastal Plain, 2012-14. AB - Historically, lead poisoning through lead shot ingestion was one of the largest health issues affecting waterfowl in North America. Lead shot was banned for use in waterfowl hunting in the US in 1991 and was banned in Canada in 1997. However, biologists need to understand how, and if, lead shot remaining in the environment will continue to impact waterfowl. Our goal was to estimate lead and nontoxic shot consumption by female Northern Pintails (Anas acuta) wintering along the Texas coast. We found shot or metal fragments (or both) in the gizzards of 39 (17%) of 227 female Northern Pintails collected along the Texas coast. Of these, lead shot was found in seven gizzards, steel shot was found in 24 gizzards, and other metal and fragments were found in 20 gizzards. Some females consumed multiple shot types. Overall, shot (lead and nontoxic combined) ingestion rates were similar to those found prior to the lead shot ban in Texas (14%) and Louisiana (17%); however, lead shot ingestion rates were considerably lower, suggesting that it is becoming less available over time. All Northern Pintails that had lead shot in their gizzards were collected from coastal habitats. While it seems that lead shot ingestion by Northern Pintails has decreased since the ban was put in place, monitoring lead shot ingestion rates from different regions will provide insight into its availability in different habitats and under various environmental conditions. PMID- 26555109 TI - Low Titers of Canine Distemper Virus Antibody in Wild Fishers (Martes pennanti) in the Eastern USA. AB - Canine distemper virus (CDV) infects species in the order Carnivora. Members of the family Mustelidae are among the species most susceptible to CDV and have a high mortality rate after infection. Assessing an animal's pathogen or disease load prior to any reintroduction project is important to help protect the animal being reintroduced, as well as the wildlife and livestock in the area of relocation. We screened 58 fishers for CDV antibody prior to their release into Pennsylvania, US, as part of a reintroduction program. Five of the 58 (9%) fishers had a weak-positive reaction for CDV antibody at a dilution of 1:16. None of the fishers exhibited any clinical sign of canine distemper while being held prior to release. PMID- 26555110 TI - A NOVEL GAMMAHERPESVIRUS IN NORTHERN FUR SEALS (CALLORHINUS URSINUS) IS CLOSELY RELATED TO THE CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS) CARCINOMA-ASSOCIATED OTARINE HERPESVIRUS-1. AB - Otarine herpesvirus 1 (OtHV1) is strongly associated with California sea lion (CSL, Zalophus californianus) urogenital carcinoma, the most common cancer documented in marine mammals. In addition to CSL, OtHV1 has also been found in association with carcinoma in South American fur seals (Arctocephalus australis), demonstrating it can infect related species. Northern fur seals (NFS, Callorhinus ursinus) are sympatric with CSL, and copulation between these species has been observed; yet, there are no reports of urogenital carcinoma in NFS. We describe a new Otarine herpesvirus found in vaginal swabs from NFS, herein called OtHV4. Partial sequencing of the polymerase gene and the glycoprotein B gene revealed OtHV4 is closely related to OtHV1, with 95% homology in the region of polymerase sequenced, and phylogenetic analyses demonstrate that they are sister taxa. An OtHV4-specific hydrolysis probe quantitative PCR was developed and validated, and its use on vaginal swabs revealed 16 of 50 (32%) wild adult female NFS were positive for OtHV4. The identification of a virus highly similar to the carcinoma associated OtHV1 in a sympatric species without carcinoma suggests that comparative genomics of OtHV1 and OtHV4 may identify candidate viral oncogenes. PMID- 26555111 TI - Avioserpens in the Western Grebe (Aechmophorus occidentalis): A new Host and Geographic Record for a Dracunculoid Nematode and Implications of Migration and Climate Change. AB - We report a new host and geographic range for the dracunculoid nematode (Avioserpens sp.) in a Western Grebe (Aechmophorus occidentalis) from southern Arizona, US. This discovery underscores the importance of parasite discovery and identification in the wildlife rehabilitation setting. Climate change and weather events affect the migratory spread of unusual parasites. PMID- 26555112 TI - HERPESVIRUSES INCLUDING NOVEL GAMMAHERPESVIRUSES ARE WIDESPREAD AMONG PHOCID SEAL SPECIES IN CANADA. AB - Little is known about herpesviruses in Canadian pinnipeds. We measured prevalence of antibodies to herpesviruses in the sera from Canadian phocid seals by an indirect enzyme-linked immunosorbent assay. Wild harbor seals (Phoca vitulina) and captive harbor seals were positive for antibodies to Phocid herpesvirus 1 (PhoHV-1) at prevalences of 91% and 100%, respectively. Sera from wild hooded seals (Cystophora cristata), harp seals (Pagophilus groenlandica), and grey seals (Halichoerus grypus) were positive for antibodies to PhoHV-1 antigenically related herpesvirus antigens at 73%, 79%, and 96%, respectively. We isolated new herpesviruses in cell culture from two hunter-harvested ringed seals (Pusa hispida) in poor body condition from Ulukhaktok, Northwest Territories, Canada; one lethargic hooded seal from the St. Lawrence Estuary, Quebec, Canada; and one captive, asymptomatic harp seal from the Magdalen Islands, Quebec. Partial sequencing of the herpesvirus DNA polymerase gene revealed that all four virus isolates were closely related to PhoHV-2, a member of the Gammaherpesvirinae subfamily, with nucleotide similarity ranging between 92.8% and 95.3%. The new seal herpesviruses were genetically related to other known pinniped herpesviruses, such as PhoHV-1, Otariid herpesvirus 3, Hawaiian monk (Monachus schauinslandi) seal herpesvirus, and Phocid herpesvirus 5 with 47-48%, 55%, 77%, and 70-77% nucleotide similarities, respectively. The harp seal herpesvirus and both ringed seal herpesviruses were almost identical to each other, whereas the hooded seal herpesvirus was genetically different from the three others (92.8% nucleotide similarity), indicating detection of at least two novel seal herpesviruses. These findings are the first isolation, partial genome sequencing, and identification of seal gammaherpesviruses in three species of Canadian phocid seals; two species of which were suspected of exposure to one or more antigenically related herpesviruses based on serologic analyses. PMID- 26555113 TI - Potential Vertical Transmission of Winter Ticks (Dermacentor albipictus) from Moose (Alces americanus) Dams to Neonates. AB - North American moose (Alces americanus) frequently become infested with winter ticks (Dermacentor albipictus). During capture of neonatal moose in northeastern Minnesota, US, in May-June 2013 and 2014, we recovered adult ticks from neonates, presumably vertically transferred from dams, heretofore, not documented. Infestations on neonates may have population-level implications. PMID- 26555114 TI - First Isolation of Streptococcus halichoeri and Streptococcus phocae from a Steller Sea Lion (Eumetopias jubatus) in South Korea. AB - Streptococcus species are emerging potential pathogens in marine mammals. We report the isolation and identification of Streptococcus halichoeri and Streptococcus phocae in a Steller sea lion (Eumetopias jubatus) in South Korea. PMID- 26555115 TI - PREVALENCE, PATHOLOGY, AND RISK FACTORS ASSOCIATED WITH STREPTOCOCCUS PHOCAE INFECTION IN SOUTHERN SEA OTTERS (ENHYDRA LUTRIS NEREIS), 2004-10. AB - Recent studies have implicated beta-hemolytic streptococci as opportunistic pathogens of marine mammals, including southern sea otters (Enhydra lutris nereis), but little is known about their prevalence or pathophysiology. Herein, we focus on risk factors for sea otter infection by a single beta-hemolytic streptococcal species, Streptococcus phocae. Streptococcus phocae was first identified as a marine mammal pathogen in 1994, and the first report in southern sea otters was in 2009. Its broad host range encompasses fish, pinnipeds, cetaceans, and mustelids, with S. phocae now recognized as an important pathogen of marine species worldwide. We assessed risk factors and lesion patterns for S. phocae infection in southern sea otters. Using archival necropsy data, S. phocae prevalence was 40.5% in fresh dead otters examined 2004-10. Skin trauma of any type was identified as a significant risk factor for S. phocae infection. The risk of infection was similar regardless of the cause and relative severity of skin trauma, including mating or fight wounds, shark bite, and anthropogenic trauma. Streptococcus phocae-infected sea otters were also more likely to present with abscesses or bacterial septicemia. Our findings highlight the importance of S. phocae as an opportunistic pathogen of sea otters and suggest that the most likely portal of entry is damaged skin. Even tiny skin breaks appear to facilitate bacterial colonization, invasion, abscess formation, and systemic spread. Our data provide important insights for management and care of marine species. PMID- 26555116 TI - The dying of the light: crepuscular activity in Culicoides and impact on light trap efficacy at temperate latitudes. AB - The light trap is the tool of choice for conducting large-scale Culicoides (Diptera: Ceratopogonidae) vector surveillance programmes. Its efficacy is in doubt, however. To assess this, hourly changes in Culicoides activity over the 24 h diel were determined comparatively by way of light trapping and aerial sweeping, and correlated against light intensity. In the Netherlands, sweeping around cattle at pasture revealed that, in early summer, Culicoides are active throughout the diel, and that their abundance peaks during the crepuscular period and falls to a low during the brightest hours of the day. By contrast, the light trap was able to accumulate Culicoides only at night (i.e. after illuminance levels had dropped to 0 lux and midge activity had begun to decline). Although Culicoides chiopterus and species of the Culicoides obsoletus complex were similarly abundant around livestock, they differed critically in their hours of peak activity, being largely diurnal and nocturnal, respectively. This polarity helps to explain why, routinely, the C. obsoletus complex dominates light trap collections and C. chiopterus does not. Inability to accumulate Culicoides at light intensity levels above 0 lux means that, at ever-higher latitudes, particularly beyond 45 degrees N, the progressive northward lengthening of the twilight period will have an increasingly adverse impact upon the efficacy of the light trap as a vector surveillance tool. PMID- 26555117 TI - The Incidence and Risk Factors for Psoriatic Arthritis in Patients With Psoriasis: A Prospective Cohort Study. AB - OBJECTIVE: To estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis, and to identify risk factors for its development. METHODS: The study was designed as a prospective cohort study involving psoriasis patients who did not have a diagnosis of arthritis at the time of study enrollment. Information was collected about lifestyle habits, comorbidities, psoriasis activity, and medications. Patients who developed inflammatory arthritis or spondylitis were classified as having PsA if they fulfilled the criteria of the Classification of Psoriatic Arthritis Study group. The annual incidence of PsA was estimated using an event per person-years analysis. Cox proportional hazards models, involving fixed and time-dependent explanatory variables, were fitted to obtain estimates of the relative risk (RR) of the onset of PsA, determined in multivariate models stratified by sex and controlled for age at onset of psoriasis. RESULTS: The data obtained from the 464 patients who were followed up for 8 years were analyzed. A total of 51 patients developed PsA during the 8 years since enrollment. The annual incidence rate of PsA was 2.7 cases (95% confidence interval 2.1-3.6) per 100 psoriasis patients. The following baseline variables were associated with the development of PsA in multivariate analysis: severe psoriasis (RR 5.4, P = 0.006), low level of education (university/college versus high school incomplete RR 0.22, P = 0.005; high school graduate versus high school incomplete RR 0.30, P = 0.049), and use of retinoid medications (RR 3.4, P = 0.02). In multivariate models with time-dependent variables, psoriatic nail pitting (RR 2.5, P = 0.002) and uveitis (RR 31.5, P = 0.0002) were associated with the development of PsA. CONCLUSION: The incidence of PsA in patients with psoriasis is higher than previously reported. A severe psoriasis phenotype, presence of nail pitting, low level of education, and uveitis are predictive of the development of PsA in patients with psoriasis. PMID- 26555118 TI - Imaging the Intracellular Trafficking of APP with Photoactivatable GFP. AB - Beta-amyloid (Abeta) is the major constituent of senile plaques found in the brains of Alzheimer's disease patients. Abeta is derived from the sequential cleavage of Amyloid Precursor Protein (APP) by beta and gamma-secretases. Despite the importance of Abeta to AD pathology, the subcellular localization of these cleavages is not well established. Work in our laboratory and others implicate the endosomal/lysosomal system in APP processing after internalization from the cell surface. However, the intracellular trafficking of APP is relatively understudied. While cell-surface proteins are amendable to many labeling techniques, there are no simple methods for following the trafficking of membrane proteins from the Golgi. To this end, we created APP constructs that were tagged with photo-activatable GFP (paGFP) at the C-terminus. After synthesis, paGFP has low basal fluorescence, but it can be stimulated with 413 nm light to produce a strong, stable green fluorescence. By using the Golgi marker Galactosyl transferase coupled to Cyan Fluorescent Protein (GalT-CFP) as a target, we are able to accurately photoactivate APP in the trans-Golgi network. Photo-activated APP-paGFP can then be followed as it traffics to downstream compartments identified with fluorescently tagged compartment marker proteins for the early endosome (Rab5), the late endosome (Rab9) and the lysosome (LAMP1). Furthermore, using inhibitors to APP processing including chloroquine or the gamma-secretase inhibitor L685, 458, we are able to perform pulse-chase experiments to examine the processing of APP in single cells. We find that a large fraction of APP moves rapidly to the lysosome without appearing at the cell surface, and is then cleared from the lysosome by secretase-like cleavages. This technique demonstrates the utility of paGFP for following the trafficking and processing of intracellular proteins from the Golgi to downstream compartments. PMID- 26555119 TI - The future of pharmacogenetics in the treatment of heart failure. AB - Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises beta-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the beta-1, beta-2, alpha-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome. PMID- 26555120 TI - Future of cellular therapies in orthopaedics: Different views, one common challenge. PMID- 26555121 TI - The Devil Is in the Details: Achieving Reductions in Global Cardiovascular Disease Mortality. PMID- 26555122 TI - Health and Economic Implications of National Treatment Coverage for Cardiovascular Disease in India: Cost-Effectiveness Analysis. AB - BACKGROUND: Whether to cover cardiovascular disease costs is an increasingly pressing question for low- and middle-income countries. We sought to identify the impact of expanding national insurance to cover primary prevention, secondary prevention, and tertiary treatment for cardiovascular disease in India. METHODS AND RESULTS: We incorporated data from coverage experiments into a validated microsimulation model of myocardial infarction and stroke in India to evaluate the cost-effectiveness of alternate coverage strategies. Coverage of primary prevention alone saved 3.6 million disability-adjusted life-years (DALY) per annum at an incremental cost-effectiveness ratio of $469 per DALY averted when compared with the status quo of no coverage. Coverage of primary and secondary preventions was dominated by a strategy of covering primary prevention and tertiary treatment, which prevented 6.6 million DALYs at an incremental cost effectiveness ratio of $2241 per DALY averted, when compared with that of primary prevention alone. The combination of all 3 categories yielded the greatest impact at an incremental cost per DALY averted of $5588 when compared with coverage of primary prevention plus tertiary treatment. When compared with the status quo of no coverage, coverage of all 3 categories of prevention/treatment yielded an incremental cost-effectiveness ratio of $1331 per DALY averted. In sensitivity analyses, coverage of primary preventive treatments remained cost-effective even if adherence and access to therapy were low, but tertiary coverage would require avoiding unnecessary procedures to remain cost-effective. CONCLUSIONS: Coverage of all 3 major types of cardiovascular treatment would be expected to have high impact and reasonable cost-effectiveness in India across a broad spectrum of access and adherence levels. PMID- 26555123 TI - Individualized Risk Communication and Outreach for Primary Cardiovascular Disease Prevention in Community Health Centers: Randomized Trial. AB - BACKGROUND: Many eligible primary cardiovascular disease prevention candidates are not treated with statins. Electronic health record data can identify patients with increased cardiovascular disease risk. METHODS AND RESULTS: We performed a pragmatic randomized controlled trial at community health centers in 2 states. Participants were men aged >=35 years and women >=45 years, without cardiovascular disease or diabetes mellitus, and with a 10-year risk of coronary heart disease of at least 10%. The intervention group received telephone and mailed outreach, individualized based on patients' cardiovascular disease risk and uncontrolled risk factors, provided by lay health workers. Main outcomes included: documented discussion of medication treatment for cholesterol with a primary care clinician, receipt of statin prescription within 6 months, and low density lipoprotein (LDL)-cholesterol repeated and at least 30 mg/dL lower than baseline within 1 year. Six hundred forty-six participants (328 and 318 in the intervention and control groups, respectively) were included. At 6 months, 26.8% of intervention and 11.6% of control patients had discussed cholesterol treatment with a primary care clinician (odds ratio, 2.79; [95% confidence interval, 2.25 3.46]). Statin prescribing occurred for 10.1% in the intervention group and 6.0% in the control group (odds ratio, 1.76; [95% confidence interval, 0.90-3.45]). The cholesterol outcome did not differ, and the majority of patients did not repeat lipid levels during follow-up. CONCLUSIONS: Risk communication and lay outreach increased cholesterol treatment discussions with primary care clinicians. However, most discussions did not result in statin prescribing. For outreach to be successful, it should be combined with interventions to encourage clinicians to follow contemporary risk-based cholesterol treatment guidelines. CLINICAL TRIAL REGISTRATION: URL: http://www.clincialtrials.gov. Unique identifier: NCT01610609. PMID- 26555124 TI - Another Piece of the Puzzle: Wait Times Call for Integrated Patient, Provider, and System Solutions for Cardiac Rehabilitation. PMID- 26555125 TI - Delays in Referral and Enrolment Are Associated With Mitigated Benefits of Cardiac Rehabilitation After Coronary Artery Bypass Surgery. AB - BACKGROUND: Cardiac rehabilitation (CR) is recommended after coronary artery bypass graft surgery; however, the consequences of longer wait times to start CR have not been elucidated. METHOD AND RESULTS: Cardiopulmonary, demographic, and anthropometric assessments were conducted before and after 6 months of CR in consecutively enrolled patients from January 1995 to October 2012. Wait times were ascertained from referral forms and charts. Neighborhood characteristics were ascertained using census data and cross-referencing with patients' home geographic location. Among 6497 post- coronary artery bypass graft participants, mean and median total wait time (time from surgery to first exercise session) was 101.1+/-47.9 and 80 days, respectively. In multiple linear regression, correlates of longer total wait time and the 2 wait-time phases, time from surgery to CR referral and time from CR referral to first exercise session, were determined. Factors influencing longer wait times included female sex, greater age, being employed, less social support, longer drive time to CR, lower neighborhood socioeconomic status, higher systolic blood pressure, abdominal obesity, and a complex medical history. After adjusting for correlates of delayed entry, longer wait time for each of the total and 2 wait-time phases was significantly associated with less improvement in cardiopulmonary fitness (VO2peak; beta= 0.165, P<0.001), body fat percentage (beta=0.032, P<0.02), resting heart rate (beta=0.066, P<0.001), and poorer attendance to CR classes (beta=-0.081, P<0.001) and completion rate (beta=2.741, P<0.001). CONCLUSIONS: Strategies for timely access to CR at each phase of the process are important given the negative impact that wait time has on key clinical outcomes. This is relevant because optimizing VO2peak and attendance to CR has been shown to confer a mortality advantage. PMID- 26555127 TI - The End of Journals. PMID- 26555126 TI - Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients. AB - BACKGROUND: Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH). METHODS AND RESULTS: A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients. We also evaluate a 7th "treat all" strategy wherein all patients with RH are treated with a mineralocorticoid receptor antagonist without further testing at RH diagnosis. Changes in systolic blood pressure are subsequently converted into gains in quality-adjusted life years (QALYs) by applying National Health and Nutrition Examination Survey data on concomitant risk factors to an existing cardiovascular disease simulation model. QALYs and lifetime costs were then used to calculate incremental cost effectiveness ratios for the competing strategies. The incremental cost effectiveness ratio for the strategy of computerized tomography (CT) followed by adrenal venous sampling (AVS) was $82,000/QALY compared with treat all. Incremental cost-effectiveness ratios for CT alone and AVS alone were $200,000/QALY and $492,000/QALY; the other strategies were more costly and less effective. Integrating differential patient-reported health-related quality of life adjustments for patients with PA, and incremental cost-effectiveness ratios for screening patients with CT followed by AVS, CT alone, and AVS alone were $52,000/QALY, $114,000/QALY, and $269,000/QALY gained. CONCLUSIONS: CT scanning followed by AVS was a cost-effective strategy to screen for PA among patients with RH. PMID- 26555128 TI - Trunk muscle co-activation using functional electrical stimulation modifies center of pressure fluctuations during quiet sitting by increasing trunk stiffness. AB - BACKGROUND: The purpose of this study was to examine the impact of functional electrical stimulation (FES) induced co-activation of trunk muscles during quiet sitting. We hypothesized that FES applied to the trunk muscles will increase trunk stiffness. The objectives of this study were to: 1) compare the center of pressure (COP) fluctuations during unsupported and FES-assisted quiet sitting - an experimental study and; 2) investigate how FES influences sitting balance - an analytical (simulation) study. METHODS: The experimental study involved 15 able bodied individuals who were seated on an instrumented chair. During the experiment, COP of the body projected on the seating surface was calculated to compare sitting stability of participants during unsupported and FES-assisted quiet sitting. The analytical (simulation) study examined dynamics of quiet sitting using an inverted pendulum model, representing the body, and a proportional-derivative (PD) controller, representing the central nervous system control. This model was used to analyze the relationship between increased trunk stiffness and COP fluctuations. RESULTS: In the experimental study, the COP fluctuations showed that: i) the mean velocity, mean frequency and the power frequency were higher during FES-assisted sitting; ii) the frequency dispersion for anterior-posterior fluctuations was smaller during FES-assisted sitting; and iii) the mean distance, range and centroidal frequency did not change during FES assisted sitting. The analytical (simulation) study showed that increased mechanical stiffness of the trunk had the same effect on COP fluctuations as the FES. CONCLUSIONS: The results of this study suggest that FES applied to the key trunk muscles increases the speed of the COP fluctuations by increasing the trunk stiffness during quiet sitting. PMID- 26555129 TI - Correction: synthesis and antibiotic activity of oxazolidinone-catechol conjugates against Pseudomonas aeruginosa. AB - Correction for 'Synthesis and antibiotic activity of oxazolidinone-catechol conjugates against Pseudomonas aeruginosa' by Aurelie Paulen, et al., Org. Biomol. Chem., 2016, DOI: 10.1039/c5ob01859e. PMID- 26555131 TI - Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease. AB - BACKGROUND: Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main alpha-secretase preventing beta-amyloid (betaA) formation. METHODS: Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using beta-actin as endogenous control. RESULTS: Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication. CONCLUSION: More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression. PMID- 26555130 TI - Draft genome of the scabies mite. AB - BACKGROUND: The disease scabies, caused by the ectoparasitic mite, Sarcoptes scabiei, causes significant morbidity in humans and other mammals worldwide. However, there is limited data available regarding the molecular basis of host specificity and host-parasite interactions. Therefore, we sought to produce a draft genome for S. scabiei and use this to identify molecular markers that will be useful for phylogenetic population studies and to identify candidate protein coding genes that are critical to the unique biology of the parasite. METHODS: S. scabiei var. canis DNA was isolated from living mites and sequenced to ultra-deep coverage using paired-end technology. Sequence reads were assembled into gapped contigs using de Bruijn graph based algorithms. The assembled genome was examined for repetitive elements and gene annotation was performed using ab initio, and homology-based methods. RESULTS: The draft genome assembly was about 56.2 Mb and included a mitochondrial genome contig. The predicted proteome contained 10,644 proteins, ~67 % of which appear to have clear orthologs in other species. The genome also contained more than 140,000 simple sequence repeat loci that may be useful for population-level studies. The mitochondrial genome contained 13 protein coding loci and 20 transfer RNAs. Hundreds of candidate salivary gland protein genes were identified by comparing the scabies mite predicted proteome with sialoproteins and transcripts identified in ticks and other hematophagous arthropods. These include serpins, ferritins, reprolysins, apyrases and new members of the macrophage migration inhibitory factor (MIF) gene family. Numerous other genes coding for salivary proteins, metabolic enzymes, structural proteins, proteins that are potentially immune modulating, and vaccine candidates were identified. The genes encoding cysteine and serine protease paralogs as well as mu-type glutathione S-transferases are represented by gene clusters. S. scabiei possessed homologs for most of the 33 dust mite allergens. CONCLUSION: The draft genome is useful for advancing our understanding of the host-parasite interaction, the biology of the mite and its phylogenetic relationship to other Acari. The identification of antigen-producing genes, candidate immune modulating proteins and pathways, and genes responsible for acaricide resistance offers opportunities for developing new methods for diagnosing, treating and preventing this disease. PMID- 26555132 TI - Aneurysm of the Pulmonary Artery, a Systematic Review and Critical Analysis of Current Literature. AB - BACKGROUND: Pulmonary artery (PA) aneurysms are rare and their related complications like dissection or rupture have been so far reported in a few reports, and a systematic description of the disease is lacking. To identify patients with PA aneurysm, at high-risk for complications, is critical. We performed a systematic review of the literature to determine characteristics that could identify high-risk patients. METHOD: A systematic search strategy was established and executed in Pubmed, Embase, Cochrane Central Register of Controlled Trials and Google scholar. Case reports were included if a minimal set of data were described. RESULTS: After executing the search strategy and exclusion of non-relevant or duplicate articles, 38 original articles, reviews and 169 case reports could be included. Articles were classified in high and low pressure PA aneurysms and subdivided in six groups on basis of the causative mechanisms. PA dilatation was most common in association with pulmonary hypertension, but only one dissection was reported in 6 original articles containing 153 patients. Analysis of the case reports suggests that predictors of high-risk patients are: pulmonary hypertension in congenital heart disease, fast PA diameter growth (>2 mm/year), tissue weakness due to infection and possibly pregnancy especially in combination. Except for 2 cases, PA dissection did not occur, when the PA diameter was <75 mm and the PA pressure <50 mmHg. CONCLUSION: High-risk PA aneurysms maybe identified by evaluating: the causative mechanism(s) for PA dilatation, absolute PA diameter and growth rate and by evaluating the PA systolic pressure. PMID- 26555133 TI - ABO-Incompatible Living Kidney Transplants: Evolution of Outcomes and Immunosuppressive Management. AB - ABO-incompatible living kidney transplantation (ABO-ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO-ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO-ILKT compared with those from ABO-compatible living kidney transplantation (ABO-CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032 including 247 ABO-ILKT and 785 ABO-CLKT cases-were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO compatibility. In the past decade, ABO-ILKT and ABO-CLKT recipients yielded almost equivalent outcomes with respect to the 9-year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59-3.22, p = 0.455). The graft survival rate for ABO-ILKT conducted between 2005 and 2013 was better than that for ABO-ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13-0.72, p = 0.007). ABO-ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO incompatibility. Currently, ABO-ILKT is an acceptable treatment for patients with end-stage renal disease. PMID- 26555135 TI - Analysis of Combinatorial Epigenomic States. AB - Hundreds of distinct chemical modifications to DNA and histone amino acids have been described. Regulation exerted by these so-called epigenetic marks is vital to normal development, stability of cell identity through mitosis, and nongenetic transmission of traits between generations through meiosis. Loss of this regulation contributes to many diseases. Evidence indicates epigenetic marks function in combinations, whereby a given modification has distinct effects on local genome control, depending on which additional modifications are locally present. This review summarizes emerging methods for assessing combinatorial epigenomic states, as well as challenges and opportunities for their refinement. PMID- 26555134 TI - Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success. AB - SETTING: Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection. OBJECTIVE: To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes. DESIGN: A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation. RESULTS: Of the 696 RR-TB and HIV-infected patients initiated on RR TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count <=100 (aHR 2.1, CI 1.0-4.5), and multidrug resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1 5.4). CONCLUSIONS: Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts <= 100 to initiate ART as soon as possible after RR-TB treatment initiation. PMID- 26555136 TI - Methanosarcina Play an Important Role in Anaerobic Co-Digestion of the Seaweed Ulva lactuca: Taxonomy and Predicted Metabolism of Functional Microbial Communities. AB - Macro-algae represent an ideal resource of third generation biofuels, but their use necessitates a refinement of commonly used anaerobic digestion processes. In a previous study, contrasting mixes of dairy slurry and the macro-alga Ulva lactuca were anaerobically digested in mesophilic continuously stirred tank reactors for 40 weeks. Higher proportions of U. lactuca in the feedstock led to inhibited digestion and rapid accumulation of volatile fatty acids, requiring a reduced organic loading rate. In this study, 16S pyrosequencing was employed to characterise the microbial communities of both the weakest (R1) and strongest (R6) performing reactors from the previous work as they developed over a 39 and 27-week period respectively. Comparing the reactor communities revealed clear differences in taxonomy, predicted metabolic orientation and mechanisms of inhibition, while constrained canonical analysis (CCA) showed ammonia and biogas yield to be the strongest factors differentiating the two reactor communities. Significant biomarker taxa and predicted metabolic activities were identified for viable and failing anaerobic digestion of U. lactuca. Acetoclastic methanogens were inhibited early in R1 operation, followed by a gradual decline of hydrogenotrophic methanogens. Near-total loss of methanogens led to an accumulation of acetic acid that reduced performance of R1, while a slow decline in biogas yield in R6 could be attributed to inhibition of acetogenic rather than methanogenic activity. The improved performance of R6 is likely to have been as a result of the large Methanosarcina population, which enabled rapid removal of acetic acid, providing favourable conditions for substrate degradation. PMID- 26555137 TI - Distribution of Plasmids in Distinct Leptospira Pathogenic Species. AB - Leptospirosis, caused by pathogenic Leptospira, is a worldwide zoonotic infection. The genus Leptospira includes at least 21 species clustered into three groups--pathogens, non-pathogens, and intermediates--based on 16S rRNA phylogeny. Research on Leptospira is difficult due to slow growth and poor transformability of the pathogens. Recent identification of extrachromosomal elements besides the two chromosomes in L. interrogans has provided new insight into genome complexity of the genus Leptospira. The large size, low copy number, and high similarity of the sequence of these extrachromosomal elements with the chromosomes present challenges in isolating and detecting them without careful genome assembly. In this study, two extrachromosomal elements were identified in L. borgpetersenii serovar Ballum strain 56604 through whole genome assembly combined with S1 nuclease digestion following pulsed-field gel electrophoresis (S1-PFGE) analysis. Further, extrachromosomal elements in additional 15 Chinese epidemic strains of Leptospira, comprising L. borgpetersenii, L. weilii, and L. interrogans, were successfully separated and identified, independent of genome sequence data. Southern blot hybridization with extrachromosomal element-specific probes, designated as lcp1, lcp2 and lcp3-rep, further confirmed their occurrences as extrachromosomal elements. In total, 24 plasmids were detected in 13 out of 15 tested strains, among which 11 can hybridize with the lcp1-rep probe and 11 with the lcp2-rep probe, whereas two can hybridize with the lcp3-rep probe. None of them are likely to be species-specific. Blastp search of the lcp1, lcp2, and lcp3 rep genes with a nonredundant protein database of Leptospira species genomes showed that their homologous sequences are widely distributed among clades of pathogens but not non-pathogens or intermediates. These results suggest that the plasmids are widely distributed in Leptospira species, and further elucidation of their biological significance might contribute to our understanding of biology and infectivity of pathogenic spirochetes. PMID- 26555138 TI - Integrating intervention for substance use disorder in a healthcare setting: practice and outcomes in New York City STD clinics. AB - OBJECTIVE: This article reports the integration and outcomes of implementing intervention services for substance use disorder (SUD) in three New York City public sexually transmitted disease (STD) clinics. METHODS: The screening, brief intervention, and referral to treatment (SBIRT) service model was implemented in the STD clinics in 2008. A relational database was developed, which included screening results, service dispositions, face-to-face interviews with 6-month follow-ups, and treatment information. RESULTS: From February 2008 to the end of September 2012, 146,657 STD clinic patients 18 years or older were screened for current or past substance use disorders; 15,687 received a brief intervention; 954 received referrals to formal substance abuse treatment; 2082 were referred to substance abuse support services such as Alcoholics Anonymous (AA), and 690 were referred to mental health, social or HIV awareness services. Intervention services delivered through SBIRT resulted in improvements in multiple outcomes at 6 month follow-up. Patients who received interventions had reduced SUD risks, fewer mental health problems, and fewer unprotected sexual contacts. CONCLUSION: Delivery of SUD services in a public health setting represents a significant policy and practice change and benefits many individuals whose SUDs might otherwise be overlooked. Intervention services for substance use disorder were integrated and highly utilized in the STD setting. Further research needs to focus on the long-term impact of SUD interventions in the STD setting, their cost effectiveness, and the extent they are financially sustainable under the new healthcare law. PMID- 26555139 TI - Steric Constraints Induced Frustrated Growth of Supramolecular Nanorods in Water. AB - A unique example of supramolecular polymerisation in water based on monomers with nanomolar affinities, which yield rod-like materials with extraordinarily high thermodynamic stability, yet of finite length, is reported. A small library of charge-neutral dendritic peptide amphiphiles was prepared, with a branched nonaphenylalanine-based core that was conjugated to hydrophilic dendrons of variable steric demand. Below a critical size of the dendron, the monomers assemble into nanorod-like polymers, whereas for larger dendritic side chains frustrated growth into near isotropic particles is observed. The supramolecular morphologies observed by electron microscopy, X-ray scattering and diffusion NMR spectroscopy studies are in agreement with the mechanistic insights obtained from fitting polymerisation profiles: non-cooperative isodesmic growth leads to degrees of polymerisation that match the experimentally determined nanorod contour lengths of close to 70 nm. The reported designs for aqueous self-assembly into well-defined anisotropic particles has promising potential for biomedical applications and the development of functional supramolecular biomaterials, with emerging evidence that anisotropic shapes in carrier design outperform conventional isotropic materials for targeted imaging and therapy. PMID- 26555140 TI - Mediation of improvements in sun protective and skin self-examination behaviours: results from the healthy text study. AB - OBJECTIVE: Melanoma is on the rise, especially in Caucasian populations exposed to high ultraviolet radiation such as in Australia. This paper examined the psychological components facilitating change in skin cancer prevention or early detection behaviours following a text message intervention. METHODS: The Queensland-based participants were 18 to 42 years old, from the Healthy Text study (N = 546). Overall, 512 (94%) participants completed the 12-month follow-up questionnaires. Following the social cognitive model, potential mediators of skin self-examination (SSE) and sun protection behaviour change were examined using stepwise logistic regression models. RESULTS: At 12-month follow-up, odds of performing an SSE in the past 12 months were mediated by baseline confidence in finding time to check skin (an outcome expectation), with a change in odds ratio of 11.9% in the SSE group versus the control group when including the mediator. Odds of greater than average sun protective habits index at 12-month follow-up were mediated by (a) an attempt to get a suntan at baseline (an outcome expectation) and (b) baseline sun protective habits index, with a change in odds ratio of 10.0% and 11.8%, respectively in the SSE group versus the control group. CONCLUSIONS: Few of the suspected mediation pathways were confirmed with the exception of outcome expectations and past behaviours. Future intervention programmes could use alternative theoretical models to elucidate how improvements in health behaviours can optimally be facilitated. PMID- 26555142 TI - Bent Ferroelectric Domain Walls as Reconfigurable Metallic-Like Channels. AB - Use of ferroelectric domain-walls in future electronics requires that they are stable, rewritable conducting channels. Here we demonstrate nonthermally activated metallic-like conduction in nominally uncharged, bent, rewritable ferroelectric-ferroelastic domain-walls of the ubiquitous ferroelectric Pb(Zr,Ti)O3 using scanning force microscopy down to a temperature of 4 K. New walls created at 4 K by pressure exhibit similar robust and intrinsic conductivity. Atomic resolution electron energy-loss spectroscopy confirms the conductivity confinement at the wall. This work provides a new concept in "domain wall nanoelectronics". PMID- 26555141 TI - Composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore. AB - PURPOSE: To investigate the independent relationship of individual- and area level socio-economic status (SES) with the presence and severity of visual impairment (VI) in an Asian population. METHODS: Cross-sectional data from 9993 Chinese, Malay and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of eye Diseases (2004-2011) in Singapore. Based on the presenting visual acuity (PVA) in the better-seeing eye, VI was categorized into normal vision (logMAR<=0.30), low vision (logMAR>0.30<1.00), and blindness (logMAR>=1.00). Any VI was defined as low vision/blindness in the PVA of better seeing eye. Individual-level low-SES was defined as a composite of primary-level education, monthly income<2000 SGD and residing in 1 or 2-room public apartment. An area-level SES was assessed using a socio-economic disadvantage index (SEDI), created using 12 variables from the 2010 Singapore census. A high SEDI score indicates a relatively poor SES. Associations between SES measures and presence and severity of VI were examined using multi-level, mixed-effects logistic and multinomial regression models. RESULTS: The age-adjusted prevalence of any VI was 19.62% (low vision = 19%, blindness = 0.62%). Both individual- and area-level SES were positively associated with any VI and low vision after adjusting for confounders. The odds ratio (95% confidence interval) of any VI was 2.11(1.88 2.37) for low-SES and 1.07(1.02-1.13) per 1 standard deviation increase in SEDI. When stratified by unilateral/bilateral categories, while low SES showed significant associations with all categories, SEDI showed a significant association with bilateral low vision only. The association between low SES and any VI remained significant among all age, gender and ethnic sub-groups. Although a consistent positive association was observed between area-level SEDI and any VI, the associations were significant among participants aged 40-65 years and male. CONCLUSION: In this community-based sample of Asian adults, both individual and area-level SES were independently associated with the presence and severity of VI. PMID- 26555143 TI - Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters. AB - VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA) coupled with high-performance liquid (HPLC) or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis. PMID- 26555144 TI - Wood Specific Gravity Variations and Biomass of Central African Tree Species: The Simple Choice of the Outer Wood. AB - CONTEXT: Wood specific gravity is a key element in tropical forest ecology. It integrates many aspects of tree mechanical properties and functioning and is an important predictor of tree biomass. Wood specific gravity varies widely among and within species and also within individual trees. Notably, contrasted patterns of radial variation of wood specific gravity have been demonstrated and related to regeneration guilds (light demanding vs. shade-bearing). However, although being repeatedly invoked as a potential source of error when estimating the biomass of trees, both intraspecific and radial variations remain little studied. In this study we characterized detailed pith-to-bark wood specific gravity profiles among contrasted species prominently contributing to the biomass of the forest, i.e., the dominant species, and we quantified the consequences of such variations on the biomass. METHODS: Radial profiles of wood density at 8% moisture content were compiled for 14 dominant species in the Democratic Republic of Congo, adapting a unique 3D X-ray scanning technique at very high spatial resolution on core samples. Mean wood density estimates were validated by water displacement measurements. Wood density profiles were converted to wood specific gravity and linear mixed models were used to decompose the radial variance. Potential errors in biomass estimation were assessed by comparing the biomass estimated from the wood specific gravity measured from pith-to-bark profiles, from global repositories, and from partial information (outer wood or inner wood). RESULTS: Wood specific gravity profiles from pith-to-bark presented positive, neutral and negative trends. Positive trends mainly characterized light demanding species, increasing up to 1.8 g.cm-3 per meter for Piptadeniastrum africanum, and negative trends characterized shade-bearing species, decreasing up to 1 g.cm-3 per meter for Strombosia pustulata. The linear mixed model showed the greater part of wood specific gravity variance was explained by species only (45%) followed by a redundant part between species and regeneration guilds (36%). Despite substantial variation in wood specific gravity profiles among species and regeneration guilds, we found that values from the outer wood were strongly correlated to values from the whole profile, without any significant bias. In addition, we found that wood specific gravity from the DRYAD global repository may strongly differ depending on the species (up to 40% for Dialium pachyphyllum). MAIN CONCLUSION: Therefore, when estimating forest biomass in specific sites, we recommend the systematic collection of outer wood samples on dominant species. This should prevent the main errors in biomass estimations resulting from wood specific gravity and allow for the collection of new information to explore the intraspecific variation of mechanical properties of trees. PMID- 26555145 TI - Genetic Testing Awareness and Attitudes among Latinos: Exploring Shared Perceptions and Gender-Based Differences. AB - BACKGROUND: Latinos, whose views are infrequently examined in genomic research, may be at risk of missing out on the benefits of genomic medicine. AIMS: To explore this possibility, we conducted a qualitative study of awareness and attitudes about genetic testing among Latinos with lower acculturation in New York City. METHODS: We conducted four focus groups (7 English-speaking men, 5 Spanish-speaking men, 13 English-speaking women and 13 Spanish-speaking women) to explore factors that influence the adoption of new innovations through the discussion of genetic testing in general, and a hypothetical vignette describing a genetic test for skin cancer risk, in particular. RESULTS: Through inductive thematic text analysis of focus group transcripts, our multidisciplinary team identified themes within knowledge and attitudes, communication and sources of information, anticipated responses, factors that may increase adoption, and barriers to adoption of genetic testing. Specifically, a majority of participants expressed some degree of uncertainty regarding the purpose of genetic tests and information these tests provide, rarely discussed genetic testing with others in their social networks, and expressed concerns about the misuse of and possible adverse emotional responses to genetic information. However, participants also expressed high levels of interest in receiving a skin cancer genetic test in response to the vignette and believed that receiving actionable health information was a primary reason to consider testing. Gender-based differences in perceived barriers to testing emerged. CONCLUSIONS: The results highlight beliefs and barriers that future interventions could target to help ensure that Latinos have adequate understanding of and access to genomic medicine advances. PMID- 26555146 TI - Protective effects of ellagic acid and ozone on rat ovaries with an ischemia/reperfusion injury. AB - AIM: This study investigated the effects of the antioxidant agents, ozone (O) and ellagic acid (EA), on ischemia/reperfusion (I/R) injuries developed from an ovarian torsion-detorsion model. MATERIALS AND METHODS: Arteries in the left ovaries of rats were clamped for two hours to achieve torsion, and then the clamps were removed for a two-hour detorsion period. Thirty-five female Sprague Dawley rats were randomly divided into five groups: control: administered only with anesthesia, rats were not subjected to torsion-detorsion; I/R: subjected to torsion and subsequent detorsion, without administering any treatment agent; and I/R + EA, I/R + O and I/R + O + EA: subjected to torsion and detorsion processes and administered with EA, O or EA + O at the 75th minute of torsion. The rats were then sacrificed under general anesthesia and the ovarian tissues were excised. The tissues were homogenized and levels of glutathione reductase, catalase, superoxide dismutase and malondialdehyde (MDA) were analyzed. Tissue damage was evaluated in terms of histopathological parameters, such as hemorrhage, congestion, edema and inflammation. RESULTS: Antioxidant enzyme activity and MDA levels in the ovary tissue increased in the I/R group and decreased in the O, EA and O + EA groups (P < 0.05). Histopathological examination revealed that tissue damage in the O, EA and O + EA groups decreased in comparison with the I/R group (P < 0.05). CONCLUSIONS: These biochemical and histopathological findings suggest that EA and O are effective against ovarian I/R injury. PMID- 26555148 TI - Neuromuscular electrical stimulation-assisted gait increases muscle strength and volume in children with unilateral spastic cerebral palsy. AB - AIM: To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP). METHOD: Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control. RESULTS: At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14. INTERPRETATION: Eight weeks of daily NMES-assisted gait increases muscle volume and strength of the stimulated ankle dorsiflexors in children with unilateral spastic CP. These changes are use-dependent and do not carry over after the 8 week treatment period. Gastrocnemius volume also increased post-treatment with carryover at week 14. PMID- 26555147 TI - Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients. AB - AIM: The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. MATERIALS & METHODS: Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. RESULTS: The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71 +/- 0.28 vs 1.11+/-0.69 MUg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76 +/- 0.16 vs 0.94 +/- 0.49 MUg/mL per mg/Kg for EPHX1 c.337 CC vs TT; P<0.05 for both). Carriers of the EPHX1 c.416A>G showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13 +/- 0.08 to 0.26 +/- 0.17, p<0.05) also of CBZD to CBZE (1.74 +/- 1.06 to 3.08 +/- 2.90; P<0.05) and CDRCBZD (0.13 +/- 0.08 vs 0.24 +/- 0.19 MUg/mL per mg/Kg; P<0.05). ABCB1 3455C>T SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657 +/- 285 vs 489 +/- 231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84 +/- 4.37 vs 7.41 +/- 3.43 MUg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. CONCLUSIONS: The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy. PMID- 26555149 TI - A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip. AB - Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood brain barrier (BBB). To establish such a model, we have developed a novel blood brain barrier on a chip (B3C) that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. Rat brain endothelial cells (RBEC) isolated from neonatal rats were seeded in the vascular channels of B3C and maintained under shear flow conditions, while neonatal rat astrocytes were cultured under static conditions in the tissue compartment of the B3C. RBEC formed continuous endothelial lining with a central lumen along the length of the vascular channels of B3C and exhibited tight junction formation, as measured by the expression of zonula occludens-1 (ZO-1). ZO-1 expression significantly increased with shear flow in the vascular channels and with the presence of astrocyte conditioned medium (ACM) or astrocytes cultured in the tissue compartment. Consistent with in vivo BBB, B3C allowed endfeet-like astrocyte endothelial cell interactions through a porous interface that separates the tissue compartment containing cultured astrocytes from the cultured RBEC in the vascular channels. The permeability of fluorescent 40 kDa dextran from vascular channel to the tissue compartment significantly decreased when RBEC were cultured in the presence of astrocytes or ACM (from 41.0 +/- 0.9 x 10-6 cm/s to 2.9 +/- 1.0 x 10-6 cm/s or 1.1+/-0.4 x 10-6 cm/s, respectively). Measurement of electrical resistance in B3C further supports that the addition of ACM significantly improves the barrier function in neonatal RBEC. Moreover, B3C exhibits significantly improved barrier characteristics compared to the transwell model and B3C permeability was not significantly different from the in vivo BBB permeability in neonatal rats. In summary, we developed a first dynamic in vitro neonatal BBB on a chip (B3C) that closely mimics the in vivo microenvironment, offers the flexibility of real time analysis, and is suitable for studies of BBB function as well as screening of novel therapeutics. PMID- 26555150 TI - Determining optimal threshold for statins prescribing: individualization of statins treatment for primary prevention of cardiovascular disease. AB - RATIONALE, AIMS AND OBJECTIVES: The American College of Cardiology and American Heart Association (ACC/AHA) statin guidelines recommend that people with risk of cardio-vascular disease (CVD) >=7.5% over 10 years should be treated with statins. This recommendation ignores individual patient CVD risks and preferences. We compared the ACC/AHA guidelines to the following management strategies a) individualized statins treatment based on Framingham Risk Score (FRS), b) treat none, c) treat all. METHODS: We employed regret-based decision curve analysis to evaluate the optimal treatment strategy. We used data on 5013 participants from the second generation of the Framingham Heart Study. We assessed regret of each treatment strategy [treat according to FRS vs. treat none vs. treat all] as a function of emotionally felt loss of treatment benefits and incurred treatment harms. We calculated the difference between regret associated with one strategy compared with the other and expressed it as Net Expected Regret Difference (NERD). Two strategies are identical if NERD = 0. RESULTS: Treatment according to ACC/AHA guidelines represents the optimal strategy only if the patient values avoiding heart disease 12 times more than harms related to statins. For values of benefit/harms (B/H) <12, treatment according to FRS represents the optimal strategy. For B/H <3, 'treat none' represents equally acceptable strategy. Adopting a threshold of 10% recommended by other professional organizations would decrease over-treatment by more than 60% without significantly affecting under-treatment. CONCLUSION: Under most realistic scenarios, individualizing statins treatment, or not recommending statins at all, represents the optimal strategy for primary prevention of heart disease. PMID- 26555151 TI - Indocyanine green fluorescence mapping for sentinel lymph node biopsy in early breast cancer. AB - INTRODUCTION: A recent feasibility study (ICG-10) has confirmed high sensitivity of ICG fluorescence mapping for sentinel SLN detection in early breast cancer with 95% of nodes both blue and fluorescent. This follow-on study has specifically evaluated a combination of ICG and blue dye for SLN localization. METHODS: Fifty consecutive patients (49 female; 1 male) with unilateral clinically node negative invasive (37) and non-invasive (13) breast cancer underwent SLN biopsy with blue dye and ICG. Median patient age was 48 years and median invasive tumour size 19 mm for primary surgical patients. All patients had a normal pre-operative axillary ultrasound. Nodal and procedural detection rates were calculated for ICG alone and in combination with blue dye. RESULTS: A total of 87 nodes were retrieved with an average nodal count of 1.8 per patient (range 1-4). Eighty four nodes were blue and fluorescent and 3 fluorescent only. Nodal detection rates for ICG alone and combined with blue dye were 100% (87/87) and 96% (84/87) respectively. Metastases were present in 18 nodes (all blue and fluorescent) with 10 patients node positive overall (20%). The procedural detection rate for blue dye and ICG was 96% (48/50) and 2 patients had fluorescent only nodes which were deemed sentinel (4%). CONCLUSION: Fluorescent imaging with ICG is a sensitive, valuable and safe method for SLN biopsy. A combination of blue dye and ICG is useful dual approach when radioisotope is unavailable. ICG has the potential to be a sole tracer agent with improved patient convenience and costs. PMID- 26555152 TI - Progress in lung cancer: ASCO 2015. PMID- 26555154 TI - AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective. AB - Dysregulation of the AXL receptor tyrosine kinase has been associated with many types of cancer. It has not been until recently, however, that targeting AXL has come under the spotlight because of ever accumulating evidence of its strong correlation with poor prognosis and drug resistance. The entry of the first AXL branded inhibitor in clinical trials in 2013 marked an important milestone for the clinical validation of AXL as an anticancer target. Nevertheless, to weigh the current contribution and potential future impact of AXL inhibition in the clinic, it is fundamental to recognize that several kinase inhibitors approved or in clinical development have AXL as either a prominent secondary or even the primary target. Through this review, the chemical and biological properties of the main inhibitors targeting AXL (either intentionally or unintentionally) will be discussed, along with the prospects and challenges to translate AXL inhibitors into a bona fide therapeutic option. PMID- 26555153 TI - Environmental Polychlorinated Biphenyl Exposure and Breast Cancer Risk: A Meta Analysis of Observational Studies. AB - BACKGROUND: Association between polychlorinated biphenyl (PCB) exposure and breast cancer risk has been widely studied, but the results remain controversial. We performed a meta-analysis to evaluate the evidences from observational studies on PCB exposure and breast cancer risk. METHODS: Relevant studies with data on internal PCB dose were identified from PubMed, EMBASE, CBM and CNKI databases through November 2014. Multivariable-adjusted odds ratio (OR) with 95% confidence intervals (CIs) were applied to assess the association between PCB exposure and breast cancer risk. Heterogeneity test, sensitivity analysis, subgroup analysis and publication bias test were also performed. To further explore the association between specific groups of PCB congeners and breast cancer, we examined the PCB congeners classified, according to their structural, biological and pharmacokinetics properties, as group I (potentially estrogenic), group II (potentially anti-estrogenic and immunotoxic, dioxin-like), and group III (phenobarbital, CYP1A and CYP2B inducers, biologically persistent). RESULTS: Of 660 studies screened, 25 studies which met criteria were selected, involving a total of 12866 participants (6088 cases and 6778 controls) from eight countries. The results showed that the risk of breast cancer was associated with group II (OR = 1.23, 95% CI: 1.08-1.40) and group III (OR = 1.25, 95% CI: 1.09-1.43) PCBs, but not with group I (OR = 1.10, 95%CI: 0.97-1.24) PCBs or total PCB exposure (OR = 1.09, 95%CI: 0.97-1.22). CONCLUSIONS: Our meta-analysis based on the selected studies found group II and group III PCB exposure might contribute to the risk of breast cancer. More studies in developing countries with higher PCB levels are needed, as well as studies to explore the relationships between mixtures of organochlorine compounds and breast cancer risk. PMID- 26555155 TI - The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, Design, Methods, and Participant Characteristics. AB - Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk. PMID- 26555157 TI - The impact of imagery rescripting on memory appraisals and core beliefs in social anxiety disorder. AB - Negative mental images in social anxiety disorder (SAD) are often rooted in autobiographical memories of formative, distressing life events. In the present study, 25 participants with SAD retrieved an idiosyncratic negative mental image and associated autobiographical memory. Participants were then randomly assigned either to a single-session of imagery rescripting (IR) targeting the retrieved autobiographical memory or to a non-intervention control condition (no-IR). Outcomes were assessed one week later. Compared to control participants, those who received IR experienced substantial reduction in SAD symptoms accompanied by more positive and less negative appraisals of their autobiographical memories. Moreover, IR relative to no-IR participants reported marked shifts in the content, validity, and accuracy of their memory-derived negative core beliefs about self and others, but not about the world. Results support the promise of IR as a stand-alone intervention for SAD and suggest important directions for future research to enhance our understanding of the cognitive mechanisms that underlie its effects. PMID- 26555156 TI - MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2 dependent Akt/PDK-1/mTOR phosphorylation. AB - Myristoylated alanine-rich C kinase substrate-like 1 (MARCKSL1) plays a pivotal role in the regulation of apoptosis and has been shown to maintain antitumor and metastasis-suppressive properties. In the present study, we examined the effects of MARCKSL1 as a novel anti-angiogenic agent on the inhibition of angiogenesis mediated cell migration. MARCKSL1 also reduced vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, as well as capillary-like tubular structure formation in vitro. MARCKSL1 disrupted phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) in ovarian tumorigenesis. In addition, MARCKSL1 showed potent anti-angiogenic activity and reduced the levels of VEGF and hypoxia-inducible factor 1alpha (HIF 1alpha) expression, an essential regulator of angiogenesis. Consistently, MARCKSL1 decreased VEGF-induced phosphorylation of the PI3K/Akt signaling pathway components, including phosphoinositide-dependent protein kinase 1 (PDK-1), mammalian target of rapamycin (mTOR), tuberous sclerosis complex 2 (TSC-2), p70 ribosomal protein S6 kinase (p70S6K), and glycogen synthase kinase 3beta (GSK 3beta) protein. Collectively, our results provide evidence for the physiological/biological function of an endothelial cell system involved in angiogenesis through suppression of Akt/PDK-1/mTOR phosphorylation by interaction with VEGFR-2. PMID- 26555159 TI - Modelling the interaction between danoprevir and mericitabine in the treatment of chronic HCV infection. AB - BACKGROUND: Modelling HCV RNA decline kinetics under therapy has proven useful for characterizing treatment effectiveness. METHODS: Here we model HCV viral kinetics (VK) in 72 patients given a combination of danoprevir, a protease inhibitor, and mericitabine, a nucleoside polymerase inhibitor, for 14 days in the INFORM-1 trial. A biphasic VK model with time-varying danoprevir and mericitabine effectiveness and Bliss independence for characterizing the interaction between both drugs provided the best fit to the VK data. RESULTS: The average final antiviral effectiveness of the drug combination varied between 0.998 for 100 mg three times daily of danoprevir and 500 mg twice daily of mericitabine and 0.9998 for 600 mg twice daily of danoprevir and 1,000 mg twice daily of mericitabine. Using the individual parameters estimated from the VK data collected over 2 weeks, we were not able to reproduce the low sustained virological response rates obtained in a more recent study where patients were treated with a combination of mericitabine and ritonavir-boosted danoprevir for 24 weeks. CONCLUSIONS: This suggests that drug-resistant viruses emerge after 2 weeks of treatment and that longer studies are necessary to provide accurate predictions of longer treatment outcomes. PMID- 26555160 TI - Detection of mycobacterium avium subsp. paratuberculosis in cheeses from small ruminants in Tuscany. AB - Paratuberculosis is an infectious disease which affects mainly domestic and wild ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map). Map has been associated with human diseases like Crohn disease, type-1 diabetes, sarcoidosis, multiple sclerosis and Hashimoto's thyroiditis. The aim of this study was to determine the level of Map positivity of cheeses produced in Tuscany (Italy) as an indication of human exposure to the specific pathogen. Sampling was focused on artisanal cheeses produced without commercial starter culture from raw sheep or goat milk, on small-scale farms. Samples were tested by quantitative PCR (qPCR) and culture. Map DNA was detected in 4/7 (57.14%) goat, and in 14/25 (56%) sheep cheeses by qPCR, whereas cultivation produced a positive result in only one case. This corresponded to a goat cheese that had also reacted positively by qPCR and yielded a viable Type S (sheep) strain of Map. The Map load of the tested samples based on qPCR ranged from 6*10 to 1.8*10(4)Map cells/g of cheese. The results indicate on average 56.57% and 66.6% positivity of cheese samples and farms, respectively. Hence, the type of cheeses that were analyzed within the context of this study seem to constitute a considerable source of human exposure to Map; although the question remains of whether the Map cells were present in a viable form, since positive results were almost exclusively recorded by qPCR. PMID- 26555161 TI - A RAPD based study revealing a previously unreported wide range of mesophilic and thermophilic spore formers associated with milk powders in China. AB - Aerobic spore forming bacteria are potential milk powder contaminants and are viewed as indicators of poor quality. A total of 738 bacteria, including both mesophilic and thermophilic, isolated from twenty-five powdered milk samples representative of three types of milk powders in China were analyzed based on the random amplified polymorphic DNA (RAPD) protocol to provide insight into species diversity. Bacillus licheniformis was found to be the most prevalent bacterium with greatest diversity (~43% of the total isolates) followed by Geobacillus stearothermophilus (~21% of the total isolates). Anoxybacillus flavithermus represented only 8.5% of the total profiles. Interestingly, actinomycetes represented a major group of the isolates with the predominance of Laceyella sacchari followed by Thermoactinomyces vulgaris, altogether comprising of 7.3% of the total isolates. Out of the nineteen separate bacterial species (except five unidentified groups) recovered and identified from milk powders, twelve proved to belong to novel or previously unreported species in milk powders. Assessment and characterization of the harmful effects caused by this particular micro-flora on the quality and safety of milk powders will be worth doing in the future. PMID- 26555162 TI - Evaluation of the use of non-pathogenic porcine circovirus type 1 as a vaccine delivery virus vector to express antigenic epitopes of porcine reproductive and respiratory syndrome virus. AB - We previously demonstrated that the C-terminus of the capsid gene of porcine circovirus type 2 (PCV2) is an immune reactive epitope displayed on the surface of virions. Insertion of foreign epitope tags in the C-terminus produced infectious virions that elicited humoral immune responses against both PCV2 capsid and the inserted epitope tags, whereas mutation in the N terminus impaired viral replication. Since the non-pathogenic porcine circovirus type 1 (PCV1) shares similar genomic organization and significant sequence identity with pathogenic PCV2, in this study we evaluated whether PCV1 can serve as a vaccine delivery virus vector. Four different antigenic determinants of porcine reproductive and respiratory syndrome virus (PRRSV) were inserted in the C terminus of the PCV1 capsid gene, the infectivity and immunogenicity of the resulting viruses are determined. We showed that an insertion of 12 (PRRSV-GP2 epitope II, PRRSV-GP3 epitope I, and PRRSV-GP5 epitope I), and 14 (PRRSV-GP5 epitope IV) amino acid residues did not affect PCV1 replication. We successfully rescued and characterized four chimeric PCV1 viruses expressing PRRSV linear antigenic determinants (GP2 epitope II: aa 40-51, ASPSHVGWWSFA; GP3 epitope I: aa 61-72, QAAAEAYEPGRS; GP5 epitope I: aa 35-46, SSSNLQLIYNLT; and GP5 epitope IV: aa 187-200, TPVTRVSAEQWGRP). We demonstrated that all chimeric viruses were stable and infectious in vitro and three chimeric viruses were infectious in vivo. An immunogenicity study in pigs revealed that PCV1-VR2385EPI chimeric viruses elicited neutralizing antibodies against PRRSV-VR2385. The results have important implications for further evaluating PCV1 as a potential vaccine delivery vector. PMID- 26555163 TI - Isolation and characterization of a Far-Eastern strain of tick-borne encephalitis virus in China. AB - Tick-borne encephalitis virus (TBEV) is a leading cause of human neurological infection in many parts of Europe and Asia. Although several TBEV isolates have been reported, current understanding of the biological characteristics of a Chinese strain is limited. In this study, a Far-Eastern strain of TBEV designated WH2012 was isolated in northern China. Its genome has been sequenced and found to be closely related to other Chinese TBEV isolates. Human cell lines of neural origin exposed to WH2012 showed cytopathic effects and WH2012 replicated most efficiently in human neuroblastoma cells SK-N-SH. In addition, WH2012 possessed a pathogenic potential in the mouse model, characterized by inducing a complete paralysis in the hindlimbs with a fatal outcome. We herein describe the first data regarding biological properties of TBEV from China. This study may help future research on pathogenic mechanisms of the neurological disease induced by TBEV infection in China. PMID- 26555164 TI - Natural infection of the soil-borne fungus Rosellinia necatrix with novel mycoviruses under greenhouse conditions. AB - Fungi are an important component of the soil ecosystem. Mycoviruses have numerous potential impacts on soil fungi, including phytopathogenic fungal species. However, the diversity and ecology of mycoviruses in soil fungi is largely unexplored. Our previous work has shown that the soil-borne phytopathogenic fungus Rosellinia necatrix was infected with several novel mycoviruses after growing for 2-3 years in an apple orchard. In this study, we investigated whether natural infection of R. necatrix with mycoviruses occurs under limited conditions. Virus-free R. necatrix isolates were grown in a small bucket containing soil samples for a short time (1.5-4.5 months) under greenhouse conditions. Screening of dsRNA mycoviruses among 365 retrieved isolates showed that four, including 6-31, 6-33, 6-35, and 7-11, harbored virus-like dsRNAs. Molecular characterization of the dsRNAs revealed that three retrieved isolates, 6-31, 6-33, and 6-35 were infected with a novel endornavirus and isolate 7-11 is infected with a novel partitivirus belonging to the genus Alphapartitivirus. These novel mycoviruses had no overt biological impact on R. necatrix. Overall, this study indicates that natural infections of R. necatrix with new mycoviruses can occur under experimental soil conditions. PMID- 26555165 TI - Biological characteristics of different epidemic enterovirus 71 strains and their pathogeneses in neonatal mice and rhesus monkeys. AB - Hand, foot and mouth disease (HFMD) has been prevalent in China since 2008. Enterovirus 71 (EV71) is a common causative agent of HFMD, and various strains of EV71 are prevalent worldwide. The EV71C4 subgenotype is the most endemic strain in China. However, few studies investigating the biological characteristics and pathogeneses of different C4 strains have been reported. Therefore, the current study investigated 19 clinical EV71 strains in neonatal ICR mice and neonatal rhesus monkeys by comparing pathogenicity; the virulence of different viral passages, dosages, and routes of infection; and the effects produced by subject animal age. These 19 clinical EV71 strains, which were of the same subtype, displayed varying pathogenic effects. Three strains (HE31, 231 and 262) induced limb paralysis in neonatal ICR mice. In addition, the degree of virulence was largely dependent upon the dose, route of infection, and number of passages of the challenge virus, as well as the ages of the infected animals. The present study provides valuable basic data to enable further research into EV71 pathogenesis and to facilitate the development of new drugs and vaccines. PMID- 26555166 TI - Canine parvovirus NS1 induced apoptosis involves mitochondria, accumulation of reactive oxygen species and activation of caspases. AB - The non-structural protein (NS1) of parvoviruses plays an important role in viral replication and is thought to be responsible for inducing cell death. However, the detailed mechanism and the pathways involved in canine parvovirus type 2 NS1 (CPV2.NS1) induced apoptosis are not yet known. In the present study, we report that expression of CPV2.NS1 in HeLa cells arrests cells in G1 phase of the cell cycle and the apoptosis is mitochondria mediated as indicated by mitochondrial depolarization, release of cytochrome-c and activation of caspase 9. Treatment of cells with caspase 9 inhibitor Z-LEHD-FMK reduced the induction of apoptosis significantly. We also report that expression of CPV2.NS1 causes accumulation of reactive oxygen species (ROS) and treatment with an antioxidant reduces the ROS levels and the extent of apoptosis. Our results provide an insight into the mechanism of CPV2.NS1 induced apoptosis, which might prove valuable in developing NS1 protein as an oncolytic agent. PMID- 26555168 TI - Epigenetic Deficiencies and Replicative Stress: Driving Cancer Cells to an Early Grave. AB - Cancer cell-specific synthetic lethal interactions entail promising therapeutic possibilities. In this issue of Cancer Cell, Pfister et al. describe a synthetic lethal interaction where cancer cells deficient in H3K36me3 owing to SETD2 loss of-function mutation are strongly sensitized to inhibition of WEE1, a cell cycle controlling kinase. PMID- 26555167 TI - TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs. AB - Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration. PMID- 26555169 TI - Sugar Makes Fat by Talking to SCAP. AB - Elevated blood glucose promotes lipogenesis via activating SREBP transcription factors. Tumors exhibit increased glucose uptake and lipogenesis, but the mechanisms controlling this are poorly understood. In this issue of Cancer Cell, Cheng and colleagues find that glucose activates SREBP by stabilizing SCAP, a central regulator of the SREBP pathway. PMID- 26555170 TI - In Search of a Cure for Proteostasis-Addicted Cancer: A AAA Target Revealed. AB - Tumorigenesis is often associated with an unbalanced protein homeostasis (proteostasis) network, which sensitizes cancer cells to drugs targeting protein quality control (PQC) regulators. In this issue of Cancer Cell, Anderson and colleagues investigated the anti-cancer activity of a new class of inhibitor against a multi-functional ATPase essential for proteostasis maintenance. PMID- 26555171 TI - Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. AB - Real-time monitoring of changes in cells or cell products released from malignant lesions into the blood has opened new diagnostic avenues ("liquid biopsy"). In this issue of Cancer Cell, Best and colleagues describe that tumor-associated blood platelets provide specific information on the location and molecular composition of the primary tumor. PMID- 26555172 TI - Welcoming Treat: Astrocyte-Derived Exosomes Induce PTEN Suppression to Foster Brain Metastasis. AB - Metastasis to distant organs depends on pathological crosstalk between tumor cells and various tissue-specific stromal components. Zhang and colleagues recently demonstrated that astrocyte-derived exosomal miR-19a reversibly downregulated PTEN expression in cancer cells, thereby increasing their CCL2 secretion and recruitment of myeloid cell to promote brain metastasis. PMID- 26555173 TI - Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. AB - Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP. Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth. Thus, SCAP acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBP-dependent lipogenesis. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases. PMID- 26555174 TI - NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. AB - IkappaB kinase/nuclear [corrected] factor kappaB (IKK/NF-kappaB) signaling exhibits important yet opposing functions in hepatocarcinogenesis. Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HCC) suggesting that NF-kappaB prevents liver disease and cancer. Here, we show that complete NF-kappaB inhibition by combined LPC specific ablation of RelA, c-Rel, and RelB did not phenocopy NEMO deficiency, but constitutively active IKK2-mediated NF-kappaB activation prevented hepatocellular damage and HCC in NEMO(LPC-KO) mice. Knock-in expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) prevented hepatocyte apoptosis and HCC, while RIPK1 ablation induced TNFR1-associated death domain protein (TRADD) dependent hepatocyte apoptosis and liver tumors in NEMO(LPC-KO) mice, revealing distinct kinase-dependent and scaffolding functions of RIPK1. Collectively, these results show that NEMO prevents hepatocarcinogenesis by inhibiting RIPK1 kinase activity-driven hepatocyte apoptosis through NF-kappaB-dependent and -independent functions. PMID- 26555176 TI - SnapShot: Multiple Myeloma. AB - Multiple myeloma (MM) is a plasma cell malignancy characterized by a heterogeneous clinical presentation. Genetic abnormalities are not only key events in the origin and progression of the disease but are also useful tools for prognosis, risk stratification, and therapeutic decision making. Although still incurable, a revolution in the treatment of MM is currently ongoing, leading to a significant improvement of clinical outcome and survival. To view this SnapShot, open or download the PDF. PMID- 26555177 TI - Using Nested Contractions and a Hierarchical Tensor Format To Compute Vibrational Spectra of Molecules with Seven Atoms. AB - We propose a method for solving the vibrational Schrodinger equation with which one can compute hundreds of energy levels of seven-atom molecules using at most a few gigabytes of memory. It uses nested contractions in conjunction with the reduced-rank block power method (RRBPM) described in J. Chem. Phys. 2014, 140, 174111. Successive basis contractions are organized into a tree, the nodes of which are associated with eigenfunctions of reduced-dimension Hamiltonians. The RRBPM is used recursively to compute eigenfunctions of nodes in bases of products of reduced-dimension eigenfunctions of nodes with fewer coordinates. The corresponding vectors are tensors in what is called CP-format. The final wave functions are therefore represented in a hierarchical CP-format. Computational efficiency and accuracy are significantly improved by representing the Hamiltonian in the same hierarchical format as the wave function. We demonstrate that with this hierarchical RRBPM it is possible to compute energy levels of a 64 D coupled-oscillator model Hamiltonian and also of acetonitrile (CH3CN) and ethylene oxide (C2H4O), for which we use quartic potentials. The most accurate acetonitrile calculation uses 139 MB of memory and takes 3.2 h on a single processor. The most accurate ethylene oxide calculation uses 6.1 GB of memory and takes 14 d on 63 processors. The hierarchical RRBPM shatters the memory barrier that impedes the calculation of vibrational spectra. PMID- 26555175 TI - Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis. AB - p97 is a AAA-ATPase with multiple cellular functions, one of which is critical regulation of protein homeostasis pathways. We describe the characterization of CB-5083, a potent, selective, and orally bioavailable inhibitor of p97. Treatment of tumor cells with CB-5083 leads to accumulation of poly-ubiquitinated proteins, retention of endoplasmic reticulum-associated degradation (ERAD) substrates, and generation of irresolvable proteotoxic stress, leading to activation of the apoptotic arm of the unfolded protein response. In xenograft models, CB-5083 causes modulation of key p97-related pathways, induces apoptosis, and has antitumor activity in a broad range of both hematological and solid tumor models. Molecular determinants of CB-5083 activity include expression of genes in the ERAD pathway, providing a potential strategy for patient selection. PMID- 26555178 TI - In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose. AB - High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the contribution of omental adipose tissue to ovarian cancer progression remains understudied. Omental adipose is unusual in that it contains structures known as milky spots, which are comprised of B, T, and NK cells, macrophages, and progenitor cells surrounding dense nests of vasculature. Milky spots play a key role in the physiologic functions of the omentum, which are required for peritoneal homeostasis. We have shown that milky spots also promote ovarian cancer metastatic colonization of peritoneal adipose, a key step in the development of peritoneal metastases. Here we describe the approaches we developed to evaluate and quantify milky spots in peritoneal adipose and study their functional contribution to ovarian cancer cell metastatic colonization of omental tissues both in vivo and ex vivo. These approaches are generalizable to additional mouse models and cell lines, thus enabling the study of ovarian cancer metastasis formation from initial localization of cells to milky spot structures to the development of widespread peritoneal metastases. PMID- 26555179 TI - Atomistic electrodynamics simulations of bare and ligand-coated nanoparticles in the quantum size regime. AB - The optical properties of metallic nanoparticles with nanometre dimensions exhibit features that cannot be described by classical electrodynamics. In this quantum size regime, the near-field properties are significantly modified and depend strongly on the geometric arrangements. However, simulating realistically sized systems while retaining the atomistic description remains computationally intractable for fully quantum mechanical approaches. Here we introduce an atomistic electrodynamics model where the traditional description of nanoparticles in terms of a macroscopic homogenous dielectric constant is replaced by an atomic representation with dielectric properties that depend on the local chemical environment. This model provides a unified description of bare and ligand-coated nanoparticles, as well as strongly interacting nanoparticle dimer systems. The non-local screening owing to an inhomogeneous ligand layer is shown to drastically modify the near-field properties. This will be important to consider in optimization of plasmonic nanostructures for near-field spectroscopy and sensing applications. PMID- 26555180 TI - The intriguing realm of protein biogenesis: Facing the green co-translational protein maturation networks. AB - The ribosome is the cell's protein-making factory, a huge protein-RNA complex, that is essential to life. Determining the high-resolution structures of the stable "core" of this factory was among the major breakthroughs of the past decades, and was awarded the Nobel Prize in 2009. Now that the mysteries of the ribosome appear to be more traceable, detailed understanding of the mechanisms that regulate protein synthesis includes not only the well-known steps of initiation, elongation, and termination but also the less comprehended features of the co-translational events associated with the maturation of the nascent chains. The ribosome is a platform for co-translational events affecting the nascent polypeptide, including protein modifications, folding, targeting to various cellular compartments for integration into membrane or translocation, and proteolysis. These events are orchestrated by ribosome-associated protein biogenesis factors (RPBs), a group of a dozen or more factors that act as the "welcoming committee" for the nascent chain as it emerges from the ribosome. In plants these factors have evolved to fit the specificity of different cellular compartments: cytoplasm, mitochondria and chloroplast. This review focuses on the current state of knowledge of these factors and their interaction around the exit tunnel of dedicated ribosomes. Particular attention has been accorded to the plant system, highlighting the similarities and differences with other organisms. PMID- 26555181 TI - High-yield soluble expression, purification and characterization of human steroidogenic acute regulatory protein (StAR) fused to a cleavable Maltose Binding Protein (MBP). AB - Steroidogenic acute regulatory protein (StAR) is responsible for the rapid delivery of cholesterol to mitochondria where the lipid serves as a source for steroid hormones biosynthesis in adrenals and gonads. Despite many successful investigations, current understanding of the mechanism of StAR action is far from being completely clear. StAR was mostly obtained using denaturation/renaturation or in minor quantities in a soluble form at decreased temperatures that, presumably, limited the possibilities for its consequent detailed exploration. In our hands, existing StAR expression constructs could be bacterially expressed almost exclusively as insoluble forms, even upon decreased expression temperatures and in specific strains of Escherichia coli, and isolated protein tended to aggregate and was difficult to handle. To maximize the yield of soluble protein, optimized StAR sequence encompassing functional domain STARD1 (residues 66-285) was fused to the C-terminus of His-tagged Maltose-Binding Protein (MBP) with the possibility to cleave off the whole tag by 3C protease. The developed protocol of expression and purification comprising of a combination of subtractive immobilized metal affinity chromatography (IMAC) and size-exclusion chromatography allowed us to obtain up to 25 mg/1 L culture of completely soluble StAR protein, which was (i) homogenous according to SDS-PAGE, (ii) gave a single symmetrical peak on a gel-filtration, (iii) showed the characteristic CD spectrum and (iv) pH-dependent ability to bind a fluorescently-labeled cholesterol analogue. We conclude that our strategy provides fully soluble and native StAR protein which in future could be efficiently used for biotechnology and drug discovery aimed at modulation of steroids production. PMID- 26555182 TI - Assessment of hot flushes and vaginal dryness among obese women undergoing bariatric surgery. AB - OBJECTIVE: Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women. METHODS: This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample. CONCLUSIONS: The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss. PMID- 26555183 TI - Decoupled evolution of floral traits and climatic preferences in a clade of Neotropical Gesneriaceae. AB - BACKGROUND: Major factors influencing the phenotypic diversity of a lineage can be recognized by characterizing the extent and mode of trait evolution between related species. Here, we compared the evolutionary dynamics of traits associated with floral morphology and climatic preferences in a clade composed of the genera Codonanthopsis, Codonanthe and Nematanthus (Gesneriaceae). To test the mode and specific components that lead to phenotypic diversity in this group, we performed a Bayesian phylogenetic analysis of combined nuclear and plastid DNA sequences and modeled the evolution of quantitative traits related to flower shape and size and to climatic preferences. We propose an alternative approach to display graphically the complex dynamics of trait evolution along a phylogenetic tree using a wide range of evolutionary scenarios. RESULTS: Our results demonstrated heterogeneous trait evolution. Floral shapes displaced into separate regimes selected by the different pollinator types (hummingbirds versus insects), while floral size underwent a clade-specific evolution. Rates of evolution were higher for the clade that is hummingbird pollinated and experienced flower resupination, compared with species pollinated by bees, suggesting a relevant role of plant pollinator interactions in lowland rainforest. The evolution of temperature preferences is best explained by a model with distinct selective regimes between the Brazilian Atlantic Forest and the other biomes, whereas differentiation along the precipitation axis was characterized by higher rates, compared with temperature, and no regime or clade-specific patterns. CONCLUSIONS: Our study shows different selective regimes and clade-specific patterns in the evolution of morphological and climatic components during the diversification of Neotropical species. Our new graphical visualization tool allows the representation of trait trajectories under parameter-rich models, thus contributing to a better understanding of complex evolutionary dynamics. PMID- 26555184 TI - Absorption Features in Soil Spectra Assessment. AB - From a wide range of techniques appropriate to relate spectra measurements with soil properties, partial least squares (PLS) regression and support vector machines (SVM) are most commonly used. This is due to their predictive power and the availability of software tools. Both represent exclusively statistically based approaches and, as such, benefit from multiple responses of soil material in the spectrum. However, physical-based approaches that focus only on a single spectral feature, such as simple linear regression using selected continuum removed spectra values as a predictor variable, often provide accurate estimates. Furthermore, if this approach extends to multiple cases by taking into account three basic absorption feature parameters (area, width, and depth) of all occurring features as predictors and subjecting them to best subset selection, one can achieve even higher prediction accuracy compared with PLS regression. Here, we attempt to further extend this approach by adding two additional absorption feature parameters (left and right side area), as they can be important diagnostic markers, too. As a result, we achieved higher prediction accuracy compared with PLS regression and SVM for exchangeable soil pH, slightly higher or comparable for dithionite-citrate and ammonium oxalate extractable Fe and Mn forms, but slightly worse for oxidizable carbon content. Therefore, we suggest incorporating the multiple linear regression approach based on absorption feature parameters into existing working practices. PMID- 26555185 TI - The effect of an external hip joint stabiliser on gait function after surgery for tumours located around the circumference of the pelvis: analysis of seven cases of internal hemipelvectomy or proximal femur resection. AB - PURPOSE: Limb-sparing resection of malignant pelvic tumours provides the opportunity for patients to obtain better post-operative mobility. However, because few studies have examined in detail the gait function of patients following pelvic tumour resection, the factors affecting gait performance remain to be clarified. Here, with the laboratory-based computer-assisted gait analysis, we evaluated these patients' gait objectively and the impact of a hip-stabilising supporter on gait improvement was simultaneously examined. METHODS: Three dimensional gait analysis was performed to obtain cross-sectional data for seven post-operative patients (mean age, 42.7 years; range, 20-61 years) who underwent various types of resection, including P1/4 internal hemipelvectomy (IH), P1/2/3 IH, and proximal femur resection with prosthetic reconstruction. To assess the immediate effects of a hip joint stabiliser, we instructed subjects to walk at their self-selected preferred speed and compared gait parameters with and without use of the hip stabiliser. RESULTS: At baseline, the average walking speed was 0.75 m/s (95% CI 0.53-0.97). As shown by the intra-subject comparison, the hip stabiliser increased walking speed in all but one subject, increasing both temporal and spatial parameters. Ground reaction force of operated limbs increased for some subjects, while step length increased on at least one side in all subjects. CONCLUSIONS: Improvement in the gait parameters is indicative of better control provided by the external hip stabiliser over the affected limb. Moreover, our findings show the potential of a biomechanical approach to improve gait function following pelvic tumour resection. PMID- 26555186 TI - Detritic synovitis can mimic a Propionibacterium periprosthetic infection. AB - PURPOSE: The purpose of this article is to illustrate that the clinical findings of detritic synovitis complicating a total shoulder arthroplasty can strongly resemble those of a 'stealth' periprosthetic shoulder infection with a low virulence organism such as Propionibacterium. METHODS: We present a review of the literature and illustrate an example of detritic synovitis following a total shoulder arthroplasty. RESULTS: The combination of glenoid component loosening and humeral osteolysis after total shoulder arthroplasty are commonly attributed to periprosthetic infection with low virulence organisms, such as Propionibacterium or coagulase negative Staphylococcus. Such a periprosthetic infection can appear long after the index joint replacement. This article points out that these same findings may occur with a non-infectious process initiated by polyethylene, cement or metal debris-detritic synovitis. CONCLUSIONS: At present, the important differentiation between these two etiologies can only be ascertained by awaiting the results of cultures obtained at the time of revision surgery. PMID- 26555188 TI - Structural basis for an atypical active site of an L-aspartate/glutamate-specific racemase from Escherichia coli. AB - We determined the crystal structure of EcL-DER to elucidate protein function and substrate specificity. Unlike other asp/glu racemases, EcL-DER has an unbalanced pair of catalytic residues, Thr83/Cys197, at the active site that is crucial for L- to D-unidirectional racemase activity. EcL-DER exhibited racemase activity for both L-glutamate and L-aspartate, but had threefold higher activity for L glutamate. Based on the structure of the EcL-DER(C197S) mutant in complex with L glutamate, we determined the binding mode of the L-glutamate substrate in EcL-DER and provide a structural basis for how the protein utilizes L-glutamate as a main substrate. The unidirectionality, despite an equilibrium constant of unity, can be understood in terms of the Haldane relationship. PMID- 26555187 TI - Age- and gender-specific clinical characteristics of acute adult spine fractures in China. AB - PURPOSE: The purpose of this study was to investigate the age- and gender specific clinical characteristics of adult spine fractures in China. METHOD: A retrospective investigation was performed on consecutive patients with acute spinal fractures in 83 hospitals of 31 provinces in China between January 2010 and December 2011. All adult patients (>=16 years) with spinal column fracture were included, while pathologic, old, and periprosthetic fractures were excluded. Each patient was analysed by reviewing the medical records and initial radiographs. RESULTS: There were 54,533 adult patients with spinal column fractures, accounting for 14.57 % of overall fractures. The medium age was 57 years (range 16-100 years). There were 27,466 male patients with medium age of 49 years and 27,067 females with medium age of 63 years. The male to female ratio was 1.01:1 in study. It was 1.74:1 in patients less than 59 years, and 0.51:1 above 60 years. The most common injury site was L1, which accounted for 33.83 % of cases. In the AO classification, the 53A and 52A groups comprised 85.53 % of all fractures. CONCLUSIONS: This study demonstrates the age- and gender-specific clinical characteristics of adults spine fractures and reveals a significant relationship among ages, sex, fracture localisation and complexity of spine fractures. Using the age of patients, the likelihood of sustaining adult spine fractures is predictable. PMID- 26555189 TI - MiR-30a attenuates immunosuppressive functions of IL-1beta-elicited mesenchymal stem cells via targeting TAB3. AB - Mesenchymal stem cells (MSCs) possess the ability to modulate the immune response, and their abnormalities are related to several diseases. We previously reported that miR-30a expression significantly increased in the maternal-fetal interface during preeclampsia (PE), but the effects of miR-30a on the immunoregulatory characteristics of MSCs are unclear. In this study, we determined that miR-30a over-expression inhibited the IL-1beta-elicited activation of the nuclear factor kappaB (NF-kappaB) and JNK signaling pathways and the production of IL-6, cyclooxygenase 2 (COX2) and IL-8 by targeting transforming growth factor-beta-activated kinase 1 binding protein 3 (TAB3) in MSCs. Moreover, the over-expression of miR-30a also impaired MSCs' anti inflammatory effects on macrophages. These data demonstrated that miR-30a in MSCs may participate in the immune dysregulation of the maternal-fetal interface during PE. PMID- 26555190 TI - GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease. AB - Glial cell line-derived neurotrophic factor (GDNF) and its canonical receptor Ret can signal together or independently to fulfill many important functions in the midbrain dopaminergic (DA) system. While Ret signaling clearly impacts on the development, maintenance and regeneration of the mesostriatal DA system, the physiological functions of GDNF for the DA system are still unclear. Nevertheless, GDNF is still considered to be an excellent candidate to protect and/or regenerate the mesostriatal DA system in Parkinson disease (PD). Clinical trials with GDNF on PD patients are, however, so far inconclusive. Here, we review the current knowledge of GDNF and Ret signaling and function in the midbrain DA system, and their crosstalk with proteins and signaling pathways associated with PD. PMID- 26555192 TI - Murine cytomegalovirus (CMV) infection via the intranasal route offers a robust model of immunity upon mucosal CMV infection. AB - Cytomegalovirus (CMV) is a ubiquitous virus, causing the most common congenital infection in humans, yet a vaccine against this virus is not available. Experimental studies of immunity against CMV in animal models of infection, such as the infection of mice with mouse CMV (MCMV), have relied mainly on parenteral infection protocols, although the virus naturally transmits by mucosal routes via body fluids. To characterize the biology of infections by mucosal routes, we compared the kinetics of virus replication, latent viral load and CD8 T-cell responses in lymphoid organs upon experimental intranasal (targeting the respiratory tract) and intragastric (targeting the digestive tract) infection with systemic intraperitoneal infection of two unrelated mouse strains. We observed that intranasal infection induced robust and long-term virus replication in the lungs and salivary glands but limited replication in the spleen. CD8 T cell responses were somewhat weaker than upon intraperitoneal infection but showed similar kinetic profiles and phenotypes of antigen-specific cells. In contrast, intragastric infection resulted in abortive or poor virus replication in all tested organs and poor T-cell responses to the virus, especially at late times after infection. Consistent with the T-cell kinetics, the MCMV latent load was high in the lungs but low in the spleen of intranasally infected mice and lowest in all tested organs upon intragastric infection. In conclusion, we showed that intranasal but not intragastric infection of mice with MCMV represents a robust model to study the short- and long-term biology of CMV infection by a mucosal route. PMID- 26555191 TI - Role of arginine and lysine in the antimicrobial mechanism of histone-derived antimicrobial peptides. AB - Translocation of cell-penetrating peptides is often promoted by increased content of arginine or other guanidinium groups. However, relatively little research has considered the role of these functional groups on antimicrobial peptide activity. This study compared the activity of three histone-derived antimicrobial peptides buforin II, DesHDAP1, and parasin-with variants that contain only lysine or arginine cationic residues. These peptides operate via different mechanisms as parasin causes membrane permeabilization while buforin II and DesHDAP1 translocate into bacteria. For all peptides, antibacterial activity increased with increased arginine content. Higher arginine content increased permeabilization for parasin while it improved translocation for buforin II and DesHDAP1. These observations provide insight into the relative importance of arginine and lysine in these antimicrobial peptides. PMID- 26555194 TI - MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones. AB - BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. METHODS: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). RESULTS: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. CONCLUSIONS: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy. PMID- 26555195 TI - Do you hear the noise? The German matrix sentence test with a fixed noise level in subjects with normal hearing and hearing impairment. AB - OBJECTIVE: The aim of this study was to determine the relationship between hearing loss and speech reception threshold (SRT) in a fixed noise condition using the German Oldenburg sentence test (OLSA). DESIGN: After training with two easily-audible lists of the OLSA, SRTs were determined monaurally with headphones at a fixed noise level of 65 dB SPL using a standard adaptive procedure, converging to 50% speech intelligibility. STUDY SAMPLE: Data was obtained from 315 ears of 177 subjects with hearing losses ranging from -5 to 90 dB HL pure tone average (PTA, 0.5, 1, 2, 3 kHz). RESULTS: Two domains were identified with a linear dependence of SRT on PTA. The SRT increased with a slope of 0.094 +/- 0.006 dB SNR/dB HL (standard deviation (SD) of residuals = 1.17 dB) for PTAs < 47 dB HL and with a slope of 0.811 +/- 0.049 dB SNR/dB HL (SD of residuals = 5.54 dB) for higher PTAs. CONCLUSION: The OLSA can be applied to subjects with a wide range of hearing losses. With 65 dB SPL fixed noise presentation level the SRT is determined by listening in noise for PTAs < ~47 dB HL, and above it is determined by listening in quiet. PMID- 26555193 TI - SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma. AB - BACKGROUND: In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). METHODS: We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. RESULTS: SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. CONCLUSIONS: SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC. PMID- 26555196 TI - Association of low serum 25-hydroxyvitamin D levels with the frailty syndrome in Mexican community-dwelling elderly. AB - OBJECTIVE: Since vitamin D is an important regulator of muscle function, the effect of vitamin D deficiency on frailty syndrome has been recently studied. This cross-sectional study aimed to determine the association between 25(OH) vitamin D levels and frailty status in Mexican community-dwelling elderly. METHODS: Sample of 331 community-dwelling elderly aged 70 or older, a subset of those included in the "Coyoacan cohort" were included. 25(OH)-vitamin D assay and frailty status were measured. RESULTS: Mean age was 79.3 years and 54.1% were women. Those classified as frail were more likely to have lower Mini-Mental State Examination score (p = 0.015), more disability for instrumental activities of daily living (p < 0.001) and for activities of daily living (p < 0.001). Serum 25(OH)-vitamin D levels were lower in the frail subgroup when compared with the non-frail one (p < 0.001). Multivariate logistic regression analyses showed a significant association between intermediate tertile [odds ratios (OR) = 4.13; 95% confidence intervals (CI) 2.00-8.56] or insufficient tertile (OR = 8.95; 95% CI 2.41-33.30) of vitamin D levels and frailty even after adjusting for potential confounders. CONCLUSION: These results suggest that older adults with low 25(OH) vitamin D levels are associated with the probability to being frail compared with those with sufficient vitamin D levels. PMID- 26555197 TI - Polarity-based fractionation in proteomics: hydrophilic interaction vs reversed phase liquid chromatography. AB - During recent decades, hydrophilic interaction liquid chromatography (HILIC) ahs been introduced to fractionate or purify especially polar solutes such as peptides and proteins while reversed-phase liquid chromatography (RPLC) is also a common strategy. RPLC is also a common dimension in multidimensional chromatography. In this study, the potential of HILIC vs RPLC chromatography was compared for proteome mapping of human peripheral blood mononuclear cell extract. In HILIC a silica-based stationary phase and for RPLC a C18 column were applied. Then separated proteins were eluted to an ion trap mass spectrometry system. Our results showed that the HILIC leads to more proteins being identified in comparison to RPLC. Among the total 181 identified proteins, 56 and 38 proteins were fractionated specifically by HILIC and RPLC, respectively. In order to demonstrate this, the physicochemical properties of identified proteins such as polarity and hydrophobicity were considered. This analysis indicated that polarity may play a major role in the HILIC separation of proteins vs RPLC. Using gene ontology enrichment analysis, it was also observed that differences in physicochemical properties conform to the cellular compartment and biological features. Finally, this study highlighted the potential of HILIC and the great orthogonality of RPLC in gel-free proteomic studies. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26555198 TI - Anti-fibrillation propensity of a flavonoid baicalein against the fibrils of hen egg white lysozyme: potential therapeutics for lysozyme amyloidosis. AB - More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3 M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20-fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in Congo red assay and appearance of a network of long rope-like fibrils in transmission electron microscope (TEM) analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose-dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150-MUM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 and 450 nm, respectively, together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis. PMID- 26555199 TI - Mitigation of non-communicable diseases in developing countries with community health workers. AB - Non-communicable diseases (NCDs) are rapidly becoming priorities in developing countries. While developed countries are more prepared in terms of skilled human resources for NCD management, developing the required human resources is still a challenge in developing countries. In this context, mobilizing community health workers (CHWs) for control of NCDs seems promising. With proper training, supervision and logistical support, CHWs can participate in the detection and treatment of hypertension, diabetes, and other priority chronic diseases. Furthermore, advice and support that CHWs can provide about diet, physical activity, and other healthy lifestyle habits (such as avoidance of smoking and excessive alcohol intake) have the potential for contributing importantly to NCD programs. This paper explores the possibility of involving CHWs in developing countries for addressing NCDs. PMID- 26555200 TI - Re: "Quantitative Assessment of Optic Nerve with Diffusion Tensor Imaging in Patients with Thyroid Ophthalmopathy". PMID- 26555202 TI - Re: "Stop Blaming the Septum". PMID- 26555201 TI - Reply re: "Quantitive Assessment of Optic Nerve with Diffusion Tensor Imaging in Patients with Thyroid Orbitopathy". PMID- 26555203 TI - Reply re: "Stop Blaming the Septum". PMID- 26555204 TI - Re: "Electron Microscopic Features of Nasal Mucosa Treated with Topical and Circumostial Injection of Mitomycin C: Implications in Dacryocystorhinostomy". PMID- 26555205 TI - Reply re: "Electron Microscopic Features of Nasal Mucosa Treated with Topical and Circumostial Injection of Mitomycin-C: Implications in Dacryocystorhinostomy". PMID- 26555206 TI - Re: "Cosmetic Microdroplet Botulinum Toxin A Forehead Lift: A New Treatment Paradigm". PMID- 26555207 TI - Reply re: "Cosmetic Microdroplet Botulinum Toxin A Forehead Lift: A New Treatment Paradigm". PMID- 26555208 TI - Dacryocystitis and Failure of Dacryocystorhinostomy Associated with Tamsulosin. PMID- 26555209 TI - A Stitch in Time.... PMID- 26555210 TI - A Technique for Removal of Nasal Silastic Tubing After Lacrimal Surgery. PMID- 26555211 TI - Infectivity-associated PrP(Sc) and disease duration-associated PrP(Sc) of mouse BSE prions. AB - Disease-related prion protein (PrP(Sc)), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrP(Sc) in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrP(Sc) in the brain. Centrifugation (20,000 *g) of the brain homogenate showed that most of the PrP(Sc) was precipitated into the pellet, and the supernatant contained only a slight amount of PrP(Sc). Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrP(Sc) may be responsible for prion infectivity and that large, aggregated PrP(Sc) may contribute to determining prion disease duration. PMID- 26555212 TI - The use of systems biology and immunological big data to guide vaccine development. AB - High-throughput technologies applied to the analysis of vaccine responses are likely to reveal the mechanisms responsible for vaccine-induced protection, aid understanding of vaccine safety and help accelerate vaccine development and clinical trials. PMID- 26555213 TI - Sexual activity beneficial to cardiac patients. PMID- 26555215 TI - Correlation Between Changes in Global Knee Structures Assessed by Magnetic Resonance Imaging and Radiographic Osteoarthritis Changes Over Ten Years in a Midlife Cohort. AB - OBJECTIVE: The aim of this study was to describe the correlation between changes in structural abnormalities assessed on magnetic resonance imaging (MRI) and change in radiographic osteoarthritis (OA) over 10 years in a midlife cohort. METHODS: A total of 211 participants (mean age 45 years [range 26-61 years], 57% female) were studied at baseline, 2 years, and 10 years. Approximately one-half were adult offspring of subjects who had undergone knee replacement for OA and the remainders were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed from radiographs, while cartilage volume, cartilage defects, and meniscal tears/extrusion were assessed from MRI. Spearman ranked correlation analysis was used to describe the correlation between structural changes assessed on MRI and radiographs. Only medial tibiofemoral compartment results are presented, as the lateral compartment had limited change. RESULTS: Over 10 years, change in meniscal tears showed a moderate independent correlation with change in both JSN (rho = +0.37, P < 0.01) and osteophytes (rho = +0.31, P < 0.01) in the adjusted analysis. Meniscal extrusion (rho = +0.22, P < 0.01) and cartilage defects (rho = +0.16, P < 0.04) showed a slightly weaker independent correlation with JSN in the adjusted analysis, whereas cartilage volume loss showed no significant correlation with either of the 2 radiographic outcomes. CONCLUSION: Change in JSN is correlated with change in meniscal tears and, to a lesser extent, with meniscal extrusion and cartilage defects. In this sample, change in JSN is a composite measure that does not reflect cartilage volume loss, prompting the review of the use of JSN as an outcome measure in chondro protective drug trials. PMID- 26555216 TI - Selective Ruthenium-Catalyzed Reductive Alkoxylation and Amination of Cyclic Imides. AB - Reported herein, for the first time, is the selective ruthenium-catalyzed reductive alkoxylation and amination of phthalimides/succinimides. Notably, this novel methodology avoids hydrogenation of the aromatic ring and allows methoxylation of substituted imides with good to excellent selectivity for one of the carbonyl groups. The reported method opens the door to the development of new processes for the selective synthesis of various functionalized N-heterocyclic compounds. As an example, intramolecular reductive couplings to afford tricyclic compounds are presented for the first time. PMID- 26555217 TI - Correction: Quantifying the Elastic Property of Nine Thigh Muscles Using Magnetic Resonance Elastography. PMID- 26555214 TI - RNA polymerase II pausing as a context-dependent reader of the genome. AB - The RNA polymerase II (Pol II) transcribes all mRNA genes in eukaryotes and is among the most highly regulated enzymes in the cell. The classic model of mRNA gene regulation involves recruitment of the RNA polymerase to gene promoters in response to environmental signals. Higher eukaryotes have an additional ability to generate multiple cell types. This extra level of regulation enables each cell to interpret the same genome by committing to one of the many possible transcription programs and executing it in a precise and robust manner. Whereas multiple mechanisms are implicated in cell type-specific transcriptional regulation, how one genome can give rise to distinct transcriptional programs and what mechanisms activate and maintain the appropriate program in each cell remains unclear. This review focuses on the process of promoter-proximal Pol II pausing during early transcription elongation as a key step in context-dependent interpretation of the metazoan genome. We highlight aspects of promoter-proximal Pol II pausing, including its interplay with epigenetic mechanisms, that may enable cell type-specific regulation, and emphasize some of the pertinent questions that remain unanswered and open for investigation. PMID- 26555218 TI - Single vs multiple independent olive domestications: the jury is (still) out. PMID- 26555219 TI - Reply to Letter Regarding "Compared Efficacy of Preservation Solutions in Liver Transplantation: A Long-Term Graft Outcome Study From the European Liver Transplant Registry". PMID- 26555220 TI - Reply. PMID- 26555221 TI - Is Carotid Stenosis in Women a Gender-Related Condition? AB - BACKGROUND: We set out to study, through ultrasound examinations, the carotid bifurcation in men and women with/without carotid stenosis to look for anatomical and electrophysiologic differences. We evaluated other variables to look for differences that might explain the dissimilar behavior of this disease in the two sexes and the presence and impact of risk factors. METHODS: We examined 974 subjects aged 25 to 88 years (478 men and 496 women) in whom we considered heart rate, smoking status, and the presence of hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. Ultrasound examination of the neck vessels included measurement of intimal medial thickness (IMT), vessel diameter, and outflow area/inflow area ratio. We established plaque location, echogenicity and echostructure, and the percentage of stenosis owing to plaque and measured systolic velocity, flow direction, and the depth of detection of these parameters. We used the apnea and hyperpnea test to assess cerebrovascular reactivity. RESULTS: Hypertension and hypercholesterolemia were the most frequent risk factors. Women had a higher heart rate, whereas men had significantly greater IMT. The presence of atheromatous plaque was significantly correlated with age in both sexes, with men having a higher prevalence of carotid plaques. The sexes differed significantly with regard to plaque location, echogenicity, echostructure, and intracranial circulation. Women had a slightly higher blood flow velocity in the intracranial arteries. Risk factors affected plaque formation and extent more in men than in women. CONCLUSIONS: These findings suggest that carotid stenosis is a gender-related trait. PMID- 26555222 TI - Refractory Kaposiform Hemangioendothelioma Associated with the Chromosomal Translocation t(13;16)(q14;p13.3). AB - We report a 7-year-old male with a history of recurrent kaposiform hemangioendothelioma (KHE) in the sacral area and multiple thoracic vertebral lesions. Tumor karyotyping revealed the balanced translocation t(13;16)(q14;p13.3). He had mildly decreased platelet counts but never experienced any episodes of Kasabach-Merritt phenomenon. He was treated with vincristine for 1 year but improvement was minor. Significant clinical improvement was seen with sirolimus therapy. To the best of our knowledge, this is the first report to demonstrate that KHE is associated with a clonal karyotypic abnormality. PMID- 26555223 TI - Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types. AB - To identify the transcriptional regulatory changes that are most widespread in solid tumors, we performed a pan-cancer analysis using over 600 pairs of tumors and adjacent normal tissues profiled in The Cancer Genome Atlas (TCGA). Frequency of upregulation was calculated across mRNA expression levels, microRNA expression levels and CpG methylation sites and is provided here as a resource. Frequent tumor-associated alterations were identified using a simple statistical approach. Many of the identified changes were consistent with the increased rate of cell division in cancer, such as the overexpression of cell cycle genes and hypermethylation of PRC2 binding sites. However, we also identified proliferation independent alterations, which highlight novel pathways essential to tumor formation. Nearly all of the GABA receptors are frequently downregulated, with the gene encoding the delta subunit (GABRD) strongly upregulated as the notable exception. Metabolic genes are also frequently downregulated, particularly alcohol dehydrogenases and others consistent with the decreased role of oxidative phosphorylation in cancerous cells. Alterations in the composition of GABA receptors and metabolism may play a key role in the differentiation of cancer cells, independent of proliferation. PMID- 26555225 TI - Gender-Related Effect in Oxygenation Dynamics by Using Far-Infrared Intervention with Near-Infrared Spectroscopy Measurement: A Gender Differences Controlled Trial. AB - Many studies have indicated the microcirculation can directly respond to disease related symptoms. However, the capacity of microcirculation would vary due to the gender differences. Near-infrared spectroscopy (NIRS) is a noninvasive technique to monitor tissue oxygenation dynamics. In this study, the far-infrared (FIR) source was used for physiological intervention of microcirculation. The experimental results show that the nature difference of oxygenation status exists between male and female during FIR irradiation. Therefore, we suggest the NIRS based assessment should be calibrated with the gender-related effect for clinical diagnosis of peripheral arterial disease. PMID- 26555224 TI - Uncovering drug-responsive regulatory elements. AB - Nucleotide changes in gene regulatory elements can have a major effect on interindividual differences in drug response. For example, by reviewing all published pharmacogenomic genome-wide association studies, we show here that 96.4% of the associated single nucleotide polymorphisms reside in noncoding regions. We discuss how sequencing technologies are improving our ability to identify drug response-associated regulatory elements genome-wide and to annotate nucleotide variants within them. We highlight specific examples of how nucleotide changes in these elements can affect drug response and illustrate the techniques used to find them and functionally characterize them. Finally, we also discuss challenges in the field of drug-responsive regulatory elements that need to be considered in order to translate these findings into the clinic. PMID- 26555226 TI - Subjective memory complaints, depressive symptoms and instrumental activities of daily living in mild cognitive impairment. AB - BACKGROUND: The diagnostic relevance of subjective memory complaints (SMCs) in mild cognitive impairment (MCI) remains to be unresolved. The aim of this study is to determine clinical correlates of SMCs in MCI. Furthermore, we examined whether there are the differences due to different aspects of complaints (i.e. prospective memory (PM) versus retrospective memory (RM) complaints). METHODS: We examined the cross-sectional associations between SMCs and depressive symptoms, instrumental activities of daily living (IADL), and cognitive measures in sixty six individuals with MCI (mean age: 65.7 +/- 8.01 years). The criteria for MCI included SMCs, objective cognitive impairment, normal general cognitive function, largely intact functional activities, and absence of dementia. SMCs were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which contains 16 items describing everyday memory failure of both PM and RM. RESULTS: SMC severity (i.e. PRMQ total score) was associated with stronger depressive symptoms and worse IADL performance. SMCs were not related to cognitive measures. For PM and RM subscores, both depressive symptoms and IADL were related to the PRMQ-PM and -RM scores. The main contributors to these PM and RM scores were depressive symptoms and IADL impairment, respectively. CONCLUSIONS: This study suggests that SMCs are more associated with depressive symptoms and IADL problems than with cognitive performance in individuals with MCI. Furthermore, while PM and RM complaints are related to both depressive symptoms and IADL, the differences between these main contributors suggest that RM complaints based on IADL could be more associated with the organically driven pathological features of MCI. PMID- 26555227 TI - Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay. AB - T-cells are remarkably specific and effective when recognizing antigens in the form of peptides embedded in MHC molecules (pMHC) on the surface of Antigen Presenting Cells (APCs). This is despite T-cell antigen receptors (TCRs) exerting usually a moderate affinity (uM range) to antigen when binding is measured in vitro(1). In view of the molecular and cellular parameters contributing to T-cell antigen sensitivity, a microscopy-based methodology has been developed as a means to monitor TCR-pMHC binding in situ, as it occurs within the synapse of a live T cell and an artificial and functionalized glass-supported planar lipid bilayer (SLB), which mimics the cell membrane of an Antigen presenting Cell (APC) (2). Measurements are based on Forster Resonance Energy Transfer (FRET) between a blue and red-shifted fluorescent dye attached to the TCR and the pMHC. Because the efficiency of FRET is inversely proportional to the sixth power of the inter-dye distance, one can employ FRET signals to visualize synaptic TCR-pMHC binding. The sensitive of the microscopy approach supports detection of single molecule FRET events. This allows to determine the affinity and off-rate of synaptic TCR-pMHC interactions and in turn to interpolate the on-rate of binding. Analogous assays could be applied to measure other receptor-ligand interactions in their native environment. PMID- 26555228 TI - Enhancer of Acetyltransferase Chameau (EAChm) Is a Novel Transcriptional Co Activator. AB - Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity. PMID- 26555229 TI - Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/DeltaFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus. AB - Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs. PMID- 26555230 TI - Deciphering Depressive Mood in Relapsing-Remitting and Progressive Multiple Sclerosis and Its Consequence on Quality of Life. AB - BACKGROUND: Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the "Echelle d'Humeur Depressive" (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS). OBJECTIVES: First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR QOL). RESULTS: Regardless of their phenotype, PwMS had significantly higher EHD PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL. CONCLUSION: The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS. PMID- 26555231 TI - Host-Guest Strategy to Reversibly Control a Chloride Carrier Process with Cyclodextrins. AB - Herein, we report a reversible modular chloride transport process based on host guest competitive interactions between an imidazolium-based chloride carrier and beta-cyclodextrin. We report evidence for the formation of the supramolecular complex between 1,3-bis(2-(adamantan-1-yl)ethyl)imidazolium bis(trifluorometyl sulfonyl)imide with two beta-cyclodextrins. Through fluorescence assays in liposomes and black lipid membrane experiments, we demonstrate that the formation of the supramolecular complex results in the inhibition of the chloride transport. We show that the chloride transport process can be entirely restored in the presence of competitive adamantyl-functionalized guests. This is the first example of an entirely reversible modular chloride transport process in phospholipid bilayers involving a mobile carrier transporter and cyclodextrin supramolecular complex. PMID- 26555232 TI - Molecular Basis for Histone Acetyltransferase Regulation by Binding Partners, Associated Domains, and Autoacetylation. AB - Acetylation is a post-translational modification (PTM) that regulates chromatin dynamics and function. Dysregulation of acetylation or acetyltransferase activity has been correlated with several human diseases. Many, if not all, histone acetyltransferases (HATs) are regulated in part through tethered domains, association with binding partners, or post-translational modification, including predominantly acetylation. This review focuses on what is currently understood at the molecular level of HAT regulation as it occurs via binding partners, associated domains, and autoacetylation. PMID- 26555233 TI - The highly alloreactive nature of dual TCR T cells. AB - PURPOSE OF REVIEW: T cells can mediate allograft rejection and graft-versus-host disease (GVHD), but are necessary for tolerance and protective immunity. Identifying T-cell populations differentially responsible for these effects has been a goal in transplant research. This review describes investigation of a small subset of T cells naturally predisposed toward alloreactivity, cells expressing two T-cell receptors (TCRs). RECENT FINDINGS: Rare peripheral T cells express two alphabetaTCRs. Their impact on T-cell development and function has been uncertain. Recent work demonstrates an important role for these cells in mouse models and human hematopoietic stem cell transplant patients with acute GVHD. Dual receptor T cells are preferentially activated and expanded in vitro and in vivo by allogeneic stimulation. Genetic elimination of dual TCR expression results in loss of approximately half of the alloreactive repertoire and impedes the earliest steps of GVHD. SUMMARY: Identification of dual TCR T cells as predisposed to alloreactivity provides an opportunity to examine responses limiting transplantation. Continued investigation will reveal significant fundamental features of T-cell alloreactivity and important information about the earliest events determining allograft rejection and self-tolerance. PMID- 26555234 TI - Post-partum hemoperitoneum: Do not miss false aneurysm as a cause of bleeding. AB - A 27-year-old woman underwent a first vaginal delivery at our institution. She returned four days after delivery, presenting with abdominal pain and an unexplained drop in her hemoglobin value, without external bleeding. The initial computed tomography abdominal scan revealed an isolated diffuse hemoperitoneum. A laparoscopy did not find the cause of bleeding. A second computed tomography scan, performed 15 days later, revealed hemoperitoneum associated with a false aneurysm of the right uterine artery. Treatment consisted of embolization of the uterine arteries, with clinical success. False aneurysms are a rare cause of intra-abdominal non-exteriorized bleeding in late post-partum hemorrhage. PMID- 26555235 TI - Volume and correlates of objectively measured physical activity and sedentary time in non-Hodgkin lymphoma survivors. AB - OBJECTIVES: Few studies have measured the physical activity levels of non-Hodgkin lymphoma (NHL) survivors, and no previous studies have measured sedentary behavior levels in this population. This study used accelerometers to measure the physical activity and sedentary time levels of NHL survivors and examined the demographic, behavioral, and medical correlates of these behaviors. METHODS: A total of 156 NHL survivors (mean age = 64 years) completed a questionnaire and wore an accelerometer for seven consecutive days during waking hours. Descriptive statistics were used to describe physical activity and sedentary time levels, and linear regression was used to investigate correlates of these behaviors. RESULTS: Participants averaged 8.6 h of sedentary time per day (60% of their accelerometer wear time), 5.3 h of light-intensity physical activity (37%), and 30 min of moderate-intensity physical activity (3%). Only 12% of the participants accrued the duration of moderate-vigorous physical activity recommended by physical activity guidelines (30 min accrued in bouts of at least 10 min). Female participants, older participants, smokers, and participants with larger waist circumference had lower levels of moderate-to-vigorous intensity physical activity. Smokers and participants with larger waist circumference also had higher sedentary time levels. CONCLUSION: The NHL survivors in this study spent the majority of their waking hours sedentary, and few met physical activity guidelines. The results of this study emphasize the need for more research exploring the health consequences of sedentary behavior and physical inactivity in NHL survivors. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26555236 TI - Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box? AB - Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients. PMID- 26555237 TI - Cross-Scale Variation in Biodiversity-Environment Links Illustrated by Coastal Sandflat Communities. AB - Spatial variation in the composition of communities is the product of many biotic and environmental interactions. A neglected factor in the analysis of community distribution patterns is the multi-scale nature of the data, which has implications for understanding ecological processes and the development of conservation and environmental management practice. Drawing on recently established multivariate spatial analyses, we investigate whether including relationships between spatial structure and abiotic variables enable us to better discern patterns of species and communities across scales. Data comprised 1200 macrozoobenthic samples collected over an array of distances (30 cm to 1 km) in three New Zealand harbours, as well as commonly used abiotic variables, such as sediment characteristics and chlorophyll a concentrations, measured at the same scales. Moran's eigenvector mapping was used to extract spatial scales at which communities were structured. Benthic communities, representing primarily bivalves, polychaetes and crustaceans, were spatially structured at four spatial scales, i.e. >100 m, 50-100 m, 50-15 m, and < 15 m. A broad selection of abiotic variables contributed to the large-scale variation, whereas a more limited set explained part of the fine-scale community structure. Across all scales, less than 30% of the variation in spatial structure was captured by our analysis. The large number of species (48) making up the 10 highest species scores based on redundancy analyses illustrate the variability of species-scale associations. Our results emphasise that abiotic variables and biodiversity are related at all scales investigated and stress the importance of assessing the relationship between environmental variables and the abundance and distribution of biological assemblages across a range of different scales. PMID- 26555238 TI - Impacts of a new insurance benefit with capitated provider payment on healthcare utilization, expenditure and quality of medication prescribing in China. AB - OBJECTIVES: To assess a new Chinese insurance benefit with capitated provider payment for common diseases in outpatients. METHODS: Longitudinal health insurance claims data, health administrative data and primary care facility data were used to assess trajectories in outpatient visits, inpatient admissions, expenditure per common disease outpatient (CD/OP) visit and prescribing indicators over time. We conducted segmented regression analyses of interrupted time series data to measure changes in level and trend overtime, and cross sectional comparisons against external standards. RESULTS: The number of total outpatient visits at 46 primary care facilities (on the CD/OP benefit as of July 2012) increased by 46 895 visits/month (P = 0.004, 95% CI: 15 795-77 994); the average number of CD/OP visits reached 1.84/year/enrollee in 2012; monthly inpatient admissions dropped from 6.4 (2009) to 4.3 (2012) per 1000 enrollees; the median total expenditure per CD/OP visit dropped by CNY 15.40 (P = 0.16, 95% CI: -36.95~6.15); injectable use dropped by 7.38% (P = 0.03, 95% CI: -14.08%~ 0.68%); antibiotic use was not improved. CONCLUSIONS: Zhuhai's new CD/OP benefit with capitated provider payment has expanded access to primary care, which may have led to a reduction in expensive specialist inpatient services for CD/OP benefit enrollees. Cost awareness was likely raised, and rapidly growing expenditures were contained. Although having been partially improved, inappropriate prescribing of antibiotics and injectables was still prevalent. More explicit incentives and specific quality of care targets must be incorporated into the capitated provider payment to promote scientifically sound and cost-effective care and treatment. PMID- 26555240 TI - Fatty acid profiles of four filamentous green algae under varying culture conditions. AB - Although benthic filamentous algae are interesting targets for wastewater treatment and biotechnology, relatively little is known about their biochemical composition and variation in response to growth conditions. Fatty acid composition of four benthic filamentous green algae was determined in different culture conditions. Although the response was partly species-dependent, increasing culture age, nitrogen deprivation and dark exposure of stationary phase greatly increased both total fatty acid content (TFA) from 12-35 to 40 173mgg(-1) dry weight (DW) and the relative proportion of polyunsaturated fatty acids (PUFAs) from 21-58% to 55-87% of TFA, with dark exposure having the greatest effect. However, the main variation in fatty acid composition was between species, with Uronema being rich in C16:0 (2.3% of DW), Klebsormidium in C18:2omega6 (5.4% of DW) and Stigeoclonium in C18:3omega3 (11.1% of DW). This indicates the potential of the latter two species as potential sources of these PUFAs. PMID- 26555239 TI - Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih. AB - HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa) to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps. PMID- 26555241 TI - Effect of iron-manganese-sepiolite as heterogeneous Fenton-like catalyst on the performance and microbial community of anaerobic granular sludge treatment system. AB - Both short-term and long-term exposure experiments have been carried out to investigate the influence of iron (Fe)-manganese (Mn)-sepiolite, as a heterogeneous Fenton-like catalyst, on the performance and microbial community of anaerobic granular sludge. During the short-term exposure experiments, chemical oxygen demand (COD) removal efficiency decreased from 73.1% to 64.1% with the presence of 100mg/L of catalyst. However, long-term exposure to the catalyst did not significantly affect the COD removal efficiency (81.8%) as compared to the control (83.5%). Meanwhile, the absorption peaks of coenzyme F420 in extracellular polymeric substances (EPS) of sludge samples were remarkable by excitation-emission matrix (EEM) fluorescence spectra. After long-term exposure, the presence of the catalyst increased secretions of EPS from 83.7mg/g VSS to 89.1mg/g VSS. Further investigations with high throughput sequencing indicated that the abundance of Methanosaeta increased from 57.7% to 70.4% after long-term exposure. In bacterial communities, Proteobacteria, Firmicutes, and Synergistetes were predominant. PMID- 26555242 TI - Questionable expression of unstable DQ heterodimer containing HLA-DQA1*01:07. AB - Human leukocyte antigens (HLA)-DQA1*01:07 was identified as an HLA-DQ blank specificity that segregated with the serological HLA-A2, -B7, -DR14, -DR52 haplotype, which carried DQB1*05:03. The blank specificity of DQA1*01:07 DQB1*05:03 may be because of lack of reactivity of available typing sera, or disruption of proper assembly of DQ heterodimer. The cDNA sequence of DQA1*01:07 is nearly identical to DQA1*01:04 except for a variant at position 304, which results in the replacement of an arginine with a cysteine at 79alpha. To determine whether the DQA1*01:07 product can be expressed on cell-surface, we co expressed DQA1*01:07 with various DQB1*05 or *06 alleles in fibroblast cells. Cell-surface expression of DQ was detectable when DQA1*01:07 was co-expressed with DQB1*06:04 but undetectable with other DQB1*05 and DQB1*06 alleles, including DQB1*05:03, to which DQA1*01:07 was encoded in cis. These data suggest that DQA1*01:07 may act as a phenotypically null allele in the DQA1*01:07 DQB1*05:03 haplotype, while it can be expressed at a low level in the presences of certain DQB1*06 alleles, such as DQB1*06:04, in trans. Based on the null or low expression of DQA1*01:07 as shown in the previous and present studies, DQA1*01:07 has recently been renamed to DQA1*01:07Q, indicating its questionable expression. PMID- 26555243 TI - Novel beta-Carboline/Hydroxamic Acid Hybrids Targeting Both Histone Deacetylase and DNA Display High Anticancer Activity via Regulation of the p53 Signaling Pathway. AB - A novel series of hybrids from beta-carboline and hydroxamic acid were designed and synthesized. Several compounds (5m, 11b-d, and 11h) not only exerted significant antiproliferation activity against four human colorectal cancer (CRC) cell lines but also showed histone deacetylase inhibitory effects in vitro. The most potent compound, 11c, exhibited anticancer potency sevenfold higher than that of SAHA. 11c triggered more significant cancer cell apoptosis than did SAHA by cleavage of both PARP and caspase 3 in a dose-dependent manner. Furthermore, 11c simultaneously increased the acetylation of histone H3 and alpha-tubulin, enhanced expression of DNA damage markers histone H2AX phosphorylation and p-p53 (Ser15), and activated p53 signaling pathway in HCT116 cells. Finally, 11c showed low acute toxicity in mice and inhibited the growth of implanted human CRC in mice more potently than did SAHA. Together, 11c possessed potent antitumor activity and may be a promising candidate for the potential treatment of human CRC. PMID- 26555245 TI - Metatranscriptomic insights on gene expression and regulatory controls in Candidatus Accumulibacter phosphatis. AB - Previous studies on enhanced biological phosphorus removal (EBPR) have focused on reconstructing genomic blueprints for the model polyphosphate-accumulating organism Candidatus Accumulibacter phosphatis. Here, a time series metatranscriptome generated from enrichment cultures of Accumulibacter was used to gain insight into anerobic/aerobic metabolism and regulatory mechanisms within an EBPR cycle. Co-expressed gene clusters were identified displaying ecologically relevant trends consistent with batch cycle phases. Transcripts displaying increased abundance during anerobic acetate contact were functionally enriched in energy production and conversion, including upregulation of both cytoplasmic and membrane-bound hydrogenases demonstrating the importance of transcriptional regulation to manage energy and electron flux during anerobic acetate contact. We hypothesized and demonstrated hydrogen production after anerobic acetate contact, a previously unknown strategy for Accumulibacter to maintain redox balance. Genes involved in anerobic glycine utilization were identified and phosphorus release after anerobic glycine contact demonstrated, suggesting that Accumulibacter routes diverse carbon sources to acetyl-CoA formation via previously unrecognized pathways. A comparative genomics analysis of sequences upstream of co-expressed genes identified two statistically significant putative regulatory motifs. One palindromic motif was identified upstream of genes involved in PHA synthesis and acetate activation and is hypothesized to be a phaR binding site, hence representing a hypothetical PHA modulon. A second motif was identified ~35 base pairs (bp) upstream of a large and diverse array of genes and hence may represent a sigma factor binding site. This analysis provides a basis and framework for further investigations into Accumulibacter metabolism and the reconstruction of regulatory networks in uncultured organisms. PMID- 26555244 TI - High Prevalence and High Incidence of Coinfection with Hepatitis B, Hepatitis C, and Syphilis and Low Rate of Effective Vaccination against Hepatitis B in HIV Positive Men Who Have Sex with Men with Known Date of HIV Seroconversion in Germany. AB - OBJECTIVES: Men who have sex with men (MSM) are at higher risk for coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis than the general population. HIV infection and these coinfections accelerate disease progression reciprocally. This study evaluated the prevalence and incidence of these coinfections in HIV1-positive MSM in Germany. MATERIALS AND METHODS: As part of a nationwide, multicenter, prospective cohort study of HIV-infected MSM, plasma samples collected yearly were screened for HBsAg and antibodies to HBc, HBs, HCV, and syphilis. Samples with indications of active HBV or HCV infection were confirmed by polymerase chain reaction. Prevalence and incidence of each infection and incidence rates per study participant were calculated, and incidences over 4-year time intervals compared. RESULTS: This study screened 5,445 samples from 1,843 MSM. Median age at HIV seroconversion was 33 years. Prevalences of active, cleared, and occult HBV, and of active/cleared HCV were 1.7%, 27.1%, 0.2%, and 8.2%, respectively, and 47.5% had been effectively vaccinated against HBV. Prevalence of antibodies to Treponema pallidum and of triple or quadruple sexually transmitted infections (STIs) were 39.6% and 18.9%, respectively. Prevalence of STI, cleared HBV, HBV vaccination, and history of syphilis differed significantly among age groups. Incidences of HBV, HCV, and syphilis were 2.51, 1.54, and 4.06 per 100 person-years, respectively. Incidences of HCV and syphilis increased over time. HCV incidence was significantly higher in MSM coinfected with syphilis and living in Berlin, and syphilis incidence was significantly higher for MSM living in Berlin. DISCUSSION: Despite extensive HBV vaccination campaigns, fewer than 50% of screened MSM were effectively vaccinated, with a high proportion of HIV-positive MSM coinfected with HBV. High rates of STI coinfections in HIV-positive MSM and increasing incidences emphasize the need for better tailored campaigns for HBV vaccination and STI prevention. PMID- 26555246 TI - Stable and sporadic symbiotic communities of coral and algal holobionts. AB - Coral and algal holobionts are assemblages of macroorganisms and microorganisms, including viruses, Bacteria, Archaea, protists and fungi. Despite a decade of research, it remains unclear whether these associations are spatial-temporally stable or species-specific. We hypothesized that conflicting interpretations of the data arise from high noise associated with sporadic microbial symbionts overwhelming signatures of stable holobiont members. To test this hypothesis, the bacterial communities associated with three coral species (Acropora rosaria, Acropora hyacinthus and Porites lutea) and two algal guilds (crustose coralline algae and turf algae) from 131 samples were analyzed using a novel statistical approach termed the Abundance-Ubiquity (AU) test. The AU test determines whether a given bacterial species would be present given additional sampling effort (that is, stable) versus those species that are sporadically associated with a sample. Using the AU test, we show that coral and algal holobionts have a high-diversity group of stable symbionts. Stable symbionts are not exclusive to one species of coral or algae. No single bacterial species was ubiquitously associated with one host, showing that there is not strict heredity of the microbiome. In addition to the stable symbionts, there was a low-diversity community of sporadic symbionts whose abundance varied widely across individual holobionts of the same species. Identification of these two symbiont communities supports the holobiont model and calls into question the hologenome theory of evolution. PMID- 26555247 TI - The corrinoid cofactor of reductive dehalogenases affects dechlorination rates and extents in organohalide-respiring Dehalococcoides mccartyi. AB - Corrinoid auxotrophic organohalide-respiring Dehalococcoides mccartyi (Dhc) strains are keystone bacteria for reductive dechlorination of toxic and carcinogenic chloroorganic contaminants. We demonstrate that the lower base attached to the essential corrinoid cofactor of reductive dehalogenase (RDase) enzyme systems modulates dechlorination activity and affects the vinyl chloride (VC) RDases BvcA and VcrA differently. Amendment of 5,6-dimethylbenzimidazolyl cobamide (DMB-Cba) to Dhc strain BAV1 and strain GT cultures supported cis-1,2 dichloroethene-to-ethene reductive dechlorination at rates of 107.0 (+/-12.0) MUM and 67.4 (+/-1.4) MUM Cl(-) released per day, respectively. Strain BAV1, expressing the BvcA RDase, reductively dechlorinated VC to ethene, although at up to fivefold lower rates in cultures amended with cobamides carrying 5 methylbenzimidazole (5-MeBza), 5-methoxybenzimidazole (5-OMeBza) or benzimidazole (Bza) as the lower base. In contrast, strain GT harboring the VcrA RDase failed to grow and dechlorinate VC to ethene in medium amended with 5-OMeBza-Cba or Bza Cba. The amendment with DMB to inactive strain GT cultures restored the VC-to ethene-dechlorinating phenotype and intracellular DMB-Cba was produced, demonstrating cobamide uptake and remodeling. The distinct responses of Dhc strains with BvcA versus VcrA RDases to different cobamides implicate that the lower base exerts control over Dhc reductive dechlorination rates and extents (that is, detoxification), and therefore the dynamics of Dhc strains with discrete reductive dechlorination capabilities. These findings emphasize that the role of the corrinoid/lower base synthesizing community must be understood to predict strain-specific Dhc activity and achieve efficacious contaminated site cleanup. PMID- 26555249 TI - Shear thickening regimes of dense non-Brownian suspensions. AB - We propose a unifying rheological framework for dense suspensions of non-Brownian spheres, predicting the onsets of particle friction and particle inertia as distinct shear thickening mechanisms, while capturing quasistatic and soft particle rheology at high volume fractions and shear rates respectively. Discrete element method simulations that take suitable account of hydrodynamic and particle-contact interactions corroborate the model predictions, demonstrating both mechanisms of shear thickening, and showing that they can occur concurrently with carefully selected particle surface properties under certain flow conditions. Microstructural transitions associated with frictional shear thickening are presented. We find very distinctive divergences of both microstructural and dynamic variables with respect to volume fraction in the thickened and non-thickened states. PMID- 26555250 TI - A 1D model of the arterial circulation in mice. AB - At a time of growing concern over the ethics of animal experimentation, mouse models are still an indispensable source of insight into the cardiovascular system and its most frequent pathologies. Nevertheless, reference data on the murine cardiovascular anatomy and physiology are lacking. In this work, we developed and validated an in silico, one dimensional model of the murine systemic arterial tree consisting of 85 arterial segments. Detailed aortic dimensions were obtained in vivo from contrast-enhanced micro-computed tomography in 3 male, C57BL/6J anesthetized mice and 3 male ApoE(-/-) mice, all 12-weeks old. Physiological input data were gathered from a wide range of literature data. The integrated form of the Navier-Stokes equations was solved numerically to yield pressures and flows throughout the arterial network. The resulting model predictions have been validated against invasive pressure waveforms and non invasive velocity and diameter waveforms that were measured in vivo on an independent set of 47 mice. In conclusion, we present a validated one-dimensional model of the anesthetized murine cardiovascular system that can serve as a versatile tool in the field of preclinical cardiovascular research. PMID- 26555248 TI - Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. AB - Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors. PMID- 26555251 TI - Small mammals as sentinels of oil sands related contaminants and health effects in northeastern Alberta, Canada. AB - The extraction of bitumen in areas of northeastern Alberta (Canada) has been associated with the release of complex mixtures of metals, metalloids, and polycyclic aromatic compounds (PACs) to the environment. To mitigate effects on ecosystems, Canadian legislation mandates that disturbed areas be reclaimed to an ecologically sustainable state after active operations. However, as part of reclamation activities, exposure to, and effects on wildlife living in these areas is not generally assessed. To support successful reclamation, the development of efficient methods to assess exposure and health effects in potentially exposed wildlife is required. In the present study, we investigated the usefulness of two native mammalian species (deer mouse Peromyscus maniculatus, and meadow vole Microtus pennsylvanicus) as sentinels of oil sands related contaminants by examining biomarkers of exposure and indicators of biological costs. Tissue residues of 31 metals and metalloids in kidneys and muscle, activity of the hepatic detoxification enzyme EROD (as a biomarker of exposure to organic contaminants), body condition, and the relative mass of liver, kidney, spleen, and testes were compared in animals from one reclaimed area and a reference site. Deer mice from the reclaimed site had higher renal levels of Co, Se and Tl compared to animals from the reference site, which was associated with reduced body condition. Lower testis mass was another feature that distinguished mice from the reclaimed site in comparison to those from the reference site. One mouse and one vole from the reclaimed site also showed increased hepatic EROD activity. In marked contrast, no changes were evident for these variables in meadow voles. Our results show that deer mouse is a sensitive sentinel species and that the biomarkers and indicators used here are efficient means to detect local contamination and associated biological effects in native mammals inhabiting reclaimed areas on active oil sands mine sites. These field derived findings can be used by risk assessors to fill possible data gaps for mammalian wildlife in science-based environmental risk assessments for oil and gas projects. PMID- 26555252 TI - Fatigue proofing: The role of protective behaviours in mediating fatigue-related risk in a defence aviation environment. AB - In the military or emergency services, operational requirements and/or community expectations often preclude formal prescriptive working time arrangements as a practical means of reducing fatigue-related risk. In these environments, workers sometimes employ adaptive or protective behaviours informally to reduce the risk (i.e. likelihood or consequence) associated with a fatigue-related error. These informal behaviours enable employees to reduce risk while continuing to work while fatigued. In this study, we documented the use of informal protective behaviours in a group of defence aviation personnel including flight crews. Semi structured interviews were conducted to determine whether and which protective behaviours were used to mitigate fatigue-related error. The 18 participants were from aviation-specific trades and included aircrew (pilots and air-crewman) and aviation maintenance personnel (aeronautical engineers and maintenance personnel). Participants identified 147 ways in which they and/or others act to reduce the likelihood or consequence of a fatigue-related error. These formed seven categories of fatigue-reduction strategies. The two most novel categories are discussed in this paper: task-related and behaviour-based strategies. Broadly speaking, these results indicate that fatigued military flight and maintenance crews use protective 'fatigue-proofing' behaviours to reduce the likelihood and/or consequence of fatigue-related error and were aware of the potential benefits. It is also important to note that these behaviours are not typically part of the formal safety management system. Rather, they have evolved spontaneously as part of the culture around protecting team performance under adverse operating conditions. When compared with previous similar studies, aviation personnel were more readily able to understand the idea of fatigue proofing than those from a fire-fighting background. These differences were thought to reflect different cultural attitudes toward error and formal training using principles of Crew Resource Management and Threat and Error Management. PMID- 26555254 TI - Bull's eye maculopathy in an HIV-positive patient receiving ritonavir. AB - Retinal toxicity involving the macula as a complication of the antiretroviral protease inhibitor ritonavir has been described in a few cases. We report retinal pigment epitheliopathy involving the macula with a bull's eye pattern in a 36 year-old man with well-controlled HIV receiving ritonavir with gradually progressive bilateral vision loss. PMID- 26555258 TI - Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin Is Mechanism-based. AB - Indolmycin is a natural tryptophan analog that competes with tryptophan for binding to tryptophanyl-tRNA synthetase (TrpRS) enzymes. Bacterial and eukaryotic cytosolic TrpRSs have comparable affinities for tryptophan (Km ~ 2 MUm), and yet only bacterial TrpRSs are inhibited by indolmycin. Despite the similarity between these ligands, Bacillus stearothermophilus (Bs)TrpRS preferentially binds indolmycin ~1500-fold more tightly than its tryptophan substrate. Kinetic characterization and crystallographic analysis of BsTrpRS allowed us to probe novel aspects of indolmycin inhibitory action. Previous work had revealed that long range coupling to residues within an allosteric region called the D1 switch of BsTrpRS positions the Mg(2+) ion in a manner that allows it to assist in transition state stabilization. The Mg(2+) ion in the inhibited complex forms significantly closer contacts with non-bridging oxygen atoms from each phosphate group of ATP and three water molecules than occur in the (presumably catalytically competent) pre-transition state (preTS) crystal structures. We propose that this altered coordination stabilizes a ground state Mg(2+).ATP configuration, accounting for the high affinity inhibition of BsTrpRS by indolmycin. Conversely, both the ATP configuration and Mg(2+) coordination in the human cytosolic (Hc)TrpRS preTS structure differ greatly from the BsTrpRS preTS structure. The effect of these differences is that catalysis occurs via a different transition state stabilization mechanism in HcTrpRS with a yet-to-be determined role for Mg(2+). Modeling indolmycin into the tryptophan binding site points to steric hindrance and an inability to retain the interactions used for tryptophan substrate recognition as causes for the 1000-fold weaker indolmycin affinity to HcTrpRS. PMID- 26555259 TI - Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-beta (TGF-beta)/Smad Signaling. AB - TGF-beta is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-beta signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-beta signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-beta signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-beta signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-beta signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive charged basic region including the L3/beta8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-beta signaling by Smad7. PMID- 26555260 TI - Chronic Hyperinsulinemia Causes Selective Insulin Resistance and Down-regulates Uncoupling Protein 3 (UCP3) through the Activation of Sterol Regulatory Element binding Protein (SREBP)-1 Transcription Factor in the Mouse Heart. AB - The risk for heart failure and death after myocardial infarction is abnormally high in diabetic subjects. We and others have shown previously that mitochondrial uncoupling protein 3 (UCP3) improves functional recovery of the rodent heart during reperfusion. Here, we demonstrate that pharmacological induction of hyperinsulinemia in mice down-regulates myocardial UCP3. Decreased UCP3 expression was linked to the development of selective insulin resistance in the heart, characterized by decreased basal activity of Akt but preserved activity of the p44/42 mitogen-activated protein kinase, and overactivation of the sterol regulatory element-binding protein (SREBP)-1-mediated lipogenic program. In cultured myocytes, insulin treatment and SREBP-1 overexpression decreased, whereas SREBP-1 interference increased, peroxisome proliferator-activated receptor-stimulated expression of UCP3. Promoter deletion and site-directed mutagenesis identified three functional sterol regulatory elements in the vicinity of a known complex intronic enhancer. Increased binding of SREBP-1 to this DNA region was confirmed in the heart of hyperinsulinemic mice. In conclusion, we describe a hitherto unknown regulatory mechanism by which insulin inhibits cardiac UCP3 expression through activation of the lipogenic factor SREBP 1. Sustained down-regulation of cardiac UCP3 by hyperinsulinemia may partly explain the poor prognosis of type 2 diabetic patients after myocardial infarction. PMID- 26555262 TI - Transmembrane Topologies of Ca2+-permeable Mechanosensitive Channels MCA1 and MCA2 in Arabidopsis thaliana. AB - Sensing mechanical stresses, including touch, stretch, compression, and gravity, is crucial for growth and development in plants. A good mechanosensor candidate is the Ca(2+)-permeable mechanosensitive (MS) channel, the pore of which opens to permeate Ca(2+) in response to mechanical stresses. However, the structure function relationships of plant MS channels are poorly understood. Arabidopsis MCA1 and MCA2 form a homotetramer and exhibit Ca(2+)-permeable MS channel activity; however, their structures have only been partially elucidated. The transmembrane topologies of these ion channels need to be determined in more detail to elucidate the underlying regulatory mechanisms. We herein determined the topologies of MCA1 and MCA2 using two independent methods, the Suc2C reporter and split-ubiquitin yeast two-hybrid methods, and found that both proteins are single-pass type I integral membrane proteins with extracellular N termini and intracellular C termini. These results imply that an EF hand-like motif, coiled coil motif, and plac8 motif are all present in the cytoplasm. Thus, the activities of both channels can be regulated by intracellular Ca(2+) and protein interactions. PMID- 26555261 TI - Myocardin-related Transcription Factor Regulates Nox4 Protein Expression: LINKING CYTOSKELETAL ORGANIZATION TO REDOX STATE. AB - TGFbeta-induced expression of the NADPH oxidase Nox4 is essential for fibroblast myofibroblast transition. Rho has been implicated in Nox4 regulation, but the underlying mechanisms are largely unknown. Myocardin-related transcription factor (MRTF), a Rho/actin polymerization-controlled coactivator of serum response factor, drives myofibroblast transition from various precursors. We have shown that TGFbeta is necessary but insufficient for epithelial-myofibroblast transition in intact epithelia; the other prerequisite is the uncoupling of intercellular contacts, which induces Rho-dependent nuclear translocation of MRTF. Because the Nox4 promoter harbors a serum response factor/MRTF cis-element (CC(A/T)6GG box), we asked if MRTF (and thus cytoskeleton organization) could regulate Nox4 expression. We show that Nox4 protein is robustly induced in kidney tubular cells exclusively by combined application of contact uncoupling and TGFbeta. Nox4 knockdown abrogates epithelial-myofibroblast transition-associated reactive oxygen species production. Laser capture microdissection reveals increased Nox4 expression in the tubular epithelium also during obstructive nephropathy. MRTF down-regulation/inhibition suppresses TGFbeta/contact disruption-provoked Nox4 protein and mRNA expression, Nox4 promoter activation, and reactive oxygen species production. Mutation of the CC(A/T)6GG box eliminates the synergistic activation of the Nox4 promoter. Jasplakinolide-induced actin polymerization synergizes with TGFbeta to facilitate MRTF-dependent Nox4 mRNA expression/promoter activation. Moreover, MRTF inhibition prevents Nox4 expression during TGFbeta-induced fibroblast-myofibroblast transition as well. Although necessary, MRTF is insufficient; Nox4 expression also requires TGFbeta activated Smad3 and TAZ/YAP, two contact- and cytoskeleton-regulated Smad3 interacting coactivators. Down-regulation/inhibition of TAZ/YAP mitigates injury induced epithelial Nox4 expression in vitro and in vivo. These findings uncover new MRTF- and TAZ/YAP-dependent mechanisms, which link cytoskeleton remodeling and redox state and impact epithelial plasticity and myofibroblast transition. PMID- 26555263 TI - The Structural and Functional Characterization of Mammalian ADP-dependent Glucokinase. AB - The enzyme-catalyzed phosphorylation of glucose to glucose-6-phosphate is a reaction central to the metabolism of all life. ADP-dependent glucokinase (ADPGK) catalyzes glucose-6-phosphate production, utilizing ADP as a phosphoryl donor in contrast to the more well characterized ATP-requiring hexokinases. ADPGK is found in Archaea and metazoa; in Archaea, ADPGK participates in a glycolytic role, but a function in most eukaryotic cell types remains unknown. We have determined structures of the eukaryotic ADPGK revealing a ribokinase-like tertiary fold similar to archaeal orthologues but with significant differences in some secondary structural elements. Both the unliganded and the AMP-bound ADPGK structures are in the "open" conformation. The structures reveal the presence of a disulfide bond between conserved cysteines that is positioned at the nucleotide binding loop of eukaryotic ADPGK. The AMP-bound ADPGK structure defines the nucleotide-binding site with one of the disulfide bond cysteines coordinating the AMP with its main chain atoms, a nucleotide-binding motif that appears unique to eukaryotic ADPGKs. Key amino acids at the active site are structurally conserved between mammalian and archaeal ADPGK, and site-directed mutagenesis has confirmed residues essential for enzymatic activity. ADPGK is substrate inhibited by high glucose concentration and shows high specificity for glucose, with no activity for other sugars, as determined by NMR spectroscopy, including 2-deoxyglucose, the glucose analogue used for tumor detection by positron emission tomography. PMID- 26555264 TI - Specific Inter-residue Interactions as Determinants of Human Monoacylglycerol Lipase Catalytic Competency: A ROLE FOR GLOBAL CONFORMATIONAL CHANGES. AB - The serine hydrolase monoacylglycerol lipase (MGL) functions as the main metabolizing enzyme of 2-arachidonoyl glycerol, an endocannabinoid signaling lipid whose elevation through genetic or pharmacological MGL ablation exerts therapeutic effects in various preclinical disease models. To inform structure based MGL inhibitor design, we report the direct NMR detection of a reversible equilibrium between active and inactive states of human MGL (hMGL) that is slow on the NMR time scale and can be modulated in a controlled manner by pH, temperature, and select point mutations. Kinetic measurements revealed that hMGL substrate turnover is rate-limited across this equilibrium. We identify a network of aromatic interactions and hydrogen bonds that regulates hMGL active-inactive state interconversion. The data highlight specific inter-residue interactions within hMGL modulating the enzymes function and implicate transitions between active (open) and inactive (closed) states of the hMGL lid domain in controlling substrate access to the enzymes active site. PMID- 26555266 TI - The High Affinity Binding Site on Plasminogen Activator Inhibitor-1 (PAI-1) for the Low Density Lipoprotein Receptor-related Protein (LRP1) Is Composed of Four Basic Residues. AB - Plasminogen activator inhibitor 1 (PAI-1) is a serpin inhibitor of the plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator, which binds tightly to the clearance and signaling receptor low density lipoprotein receptor-related protein 1 (LRP1) in both proteinase-complexed and uncomplexed forms. Binding sites for PAI-1 within LRP1 have been localized to CR clusters II and IV. Within cluster II, there is a strong preference for the triple CR domain fragment CR456. Previous mutagenesis studies to identify the binding site on PAI-1 for LRP1 have given conflicting results or implied small binding contributions incompatible with the high affinity PAI-1/LRP1 interaction. Using a highly sensitive solution fluorescence assay, we have examined binding of CR456 to arginine and lysine variants of PAI-1 and definitively identified the binding site as composed of four basic residues, Lys-69, Arg-76, Lys-80, and Lys-88. These are highly conserved among mammalian PAI-1s. Individual mutations result in a 13-800-fold increase in Kd values. We present evidence that binding involves engagement of CR4 by Lys-88, CR5 by Arg-76 and Lys-80, and CR6 by Lys-69, with the strongest interactions to CR5 and CR6. Collectively, the individual binding contributions account quantitatively for the overall PAI-1/LRP1 affinity. We propose that the greater efficiency of PAI-1.uPA complex binding and clearance by LRP1, compared with PAI-1 alone, is due solely to simultaneous binding of the uPA moiety in the complex to its receptor, thereby making binding of the PAI-1 moiety to LRP1 a two-dimensional surface-localized association. PMID- 26555265 TI - Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants. AB - Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1beta and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4 agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1beta/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS 21 as part of a heterogeneous mixture of saponins also induced IL-1beta in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo. PMID- 26555267 TI - A Novel Aldo-Keto Reductase, HdRed, from the Pacific Abalone Haliotis discus hannai, Which Reduces Alginate-derived 4-Deoxy-L-erythro-5-hexoseulose Uronic Acid to 2-Keto-3-deoxy-D-gluconate. AB - Abalone feeds on brown seaweeds and digests seaweeds' alginate with alginate lyases (EC 4.2.2.3). However, it has been unclear whether the end product of alginate lyases (i.e. unsaturated monouronate-derived 4-deoxy-L-erythro-5 hexoseulose uronic acid (DEH)) is assimilated by abalone itself, because DEH cannot be metabolized via the Embden-Meyerhof pathway of animals. Under these circumstances, we recently noticed the occurrence of an NADPH-dependent reductase, which reduced DEH to 2-keto-3-deoxy-D-gluconate, in hepatopancreas extract of the pacific abalone Haliotis discus hannai. In the present study, we characterized this enzyme to some extent. The DEH reductase, named HdRed in the present study, could be purified from the acetone-dried powder of hepatopancreas by ammonium sulfate fractionation followed by conventional column chromatographies. HdRed showed a single band of ~ 40 kDa on SDS-PAGE and reduced DEH to 2-keto-3-deoxy-D-gluconate with an optimal temperature and pH at around 50 degrees C and 7.0, respectively. HdRed exhibited no appreciable activity toward 28 authentic compounds, including aldehyde, aldose, ketose, alpha-keto-acid, uronic acid, deoxy sugar, sugar alcohol, carboxylic acid, ketone, and ester. The amino acid sequence of 371 residues of HdRed deduced from the cDNA showed 18-60% identities to those of aldo-keto reductase (AKR) superfamily enzymes, such as human aldose reductase, halophilic bacterium reductase, and sea hare norsolorinic acid (a polyketide derivative) reductase-like protein. Catalytic residues and cofactor binding residues known in AKR superfamily enzymes were fairly well conserved in HdRed. Phylogenetic analysis for HdRed and AKR superfamily enzymes indicated that HdRed is an AKR belonging to a novel family. PMID- 26555268 TI - Structure of UBE2Z Enzyme Provides Functional Insight into Specificity in the FAT10 Protein Conjugation Machinery. AB - FAT10 conjugation, a post-translational modification analogous to ubiquitination, specifically requires UBA6 and UBE2Z as its activating (E1) and conjugating (E2) enzymes. Interestingly, these enzymes can also function in ubiquitination. We have determined the crystal structure of UBE2Z and report how the different domains of this E2 enzyme are organized. We further combine our structural data with mutational analyses to understand how specificity is achieved in the FAT10 conjugation pathway. We show that specificity toward UBA6 and UBE2Z lies within the C-terminal CYCI tetrapeptide in FAT10. We also demonstrate that this motif slows down transfer rates for FAT10 from UBA6 onto UBE2Z. PMID- 26555269 TI - Reply to "Younger age at cancer diagnosis may be driven by age structure of the HCV population". PMID- 26555270 TI - Younger age at cancer diagnosis may be driven by age structure of the HCV population. PMID- 26555271 TI - Liver Bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis. AB - BACKGROUND & AIMS: Liver fibrosis is the most worrisome feature of non-alcoholic steatohepatitis (NASH). Growing evidence supports a link between hepatocyte apoptosis and liver fibrogenesis. Our aim was to determine the therapeutic efficacy and safety of liver Bid, a key pro-apoptotic molecule, suppression using RNA interference (RNAi) for the treatment of fibrosis. METHODS: First, we optimized the delivery system for Bid siRNA in mice using ten different stealth RNAi siRNAs and two lipid formulations -Invivofectamine2.0 and a newly developed Invivofectamine3.0 - that have been designed for high efficacy accumulation in the liver, assessed via real-time PCR of Bid mRNA. Next, C57BL/6 mice were placed on a choline-deficient L-amino acid defined (CDAA) diet. After 19weeks of the CDAA diet, a time point that results in severe fibrotic NASH, mice were injected with the selected Bid siRNA-Invivofectamine3.0 biweekly for three weeks. Additionally hepatocyte-specific Bid deficient (Bid(Deltahep)) mice were placed on CDAA diet for 20weeks. RESULTS: A maximum Bid knockdown was achieved at 1.5mg/kg siRNA with Invivofectamine3.0, whereas it was at 7mg/kg with Invivofectamine2.0. In NASH mice, after 3weeks of treatment, BID protein was reduced to 10% and this was associated with an improvement in liver fibrosis and inflammation associated with a marked reduction in TUNEL positive cells, caspase 3 activation, and a reduction in mitochondrial BAX and BAK. Bid(Deltahep) mice showed similar protection from fibrotic changes. CONCLUSION: Our data demonstrate that liver Bid suppression by RNAi technology, as well as hepatocyte-specific Bid deficiency, improves liver fibrosis coupled with a reduction of inflammation in experimental NASH. These findings are consistent with existing evidence that hepatocyte apoptosis triggers hepatic stellate cell activation and liver fibrosis and suggest that Bid inhibition may be useful as an antifibrotic NASH therapy. PMID- 26555272 TI - The effects of cold stress on the phenolic compounds and antioxidant capacity of grapevine (Vitis vinifera L.) leaves. AB - According to some estimates, a 70% increase in crop yield could be achieved if the environmental conditions were close to the optimum ones for a given plant, which is why the identification and control of adverse environmental effects is a top priority in many countries worldwide. This paper contains a discussion of the changes in selected elements of the secondary metabolism in the leaves of two grapevine varieties (Vitis vinifera L.) with a different degree of tolerance to cold stress during prolonged and constant low temperature stress. The analyses have shown that the more-tolerant variety was characterized by a higher content of phenolic compounds, better radical-scavenging capacity and stronger reducing power. However, the cold stress caused a decrease in the concentration of the phenolics and decreased the scavenging capacity in the leaves of both varieties. Four phenolic acids have been identified in the extracts from the leaves of both grapevines: caffeic acid, p-coumaric acid, ferulic acid and a caffeic acid derivative. Caffeic acid appeared in the highest concentrations in all the leaf extracts. Additionally, it has been noted that in the leaves of the varieties susceptible and tolerant to cold stress, the prolonged exposure to low temperature caused a considerable reduction of the content of all identified phenolic acids. The results of the analyses have demonstrated large differences in the functioning of the secondary metabolism in response to the same stressor. PMID- 26555273 TI - Elemental stoichiometry indicates predominant influence of potassium and phosphorus limitation on arbuscular mycorrhizal symbiosis in acidic soil at high altitude. AB - The functioning of high-altitude agro-ecosystems is constrained by the harsh environmental conditions, such as low temperatures, acidic soil, and low nutrient supply. It is therefore imperative to investigate the site-specific ecological stoichiometry with respect to AM symbiosis in order to maximize the arbuscular mycorrhizal (AM) benefits for the plants in such ecosystems. Here, we assess the elemental stoichiometry of four Capsicum genotypes grown on acidic soil at high altitude in Arunachal Pradesh, India. Further, we try to identify the predominant resource limitations influencing the symbioses of different Capsicum genotypes with the AM fungi. Foliar and soil elemental stoichiometric relations of Capsicum genotypes were evaluated with arbuscular mycorrhizal (AM) colonization and occurrence under field conditions. AM fungal diversity in rhizosphere, was estimated through PCR-DGGE profiling. Results demonstrated that the symbiotic interaction of various Capsicum genotypes with the AM fungi in acidic soil was not prominent in the study site as evident from the low range of root colonization (21-43.67%). In addition, despite the rich availability of carbon in plant leaves as well as in soil, the carbon-for-phosphorus trade between AMF and plants appeared to be limited. Our results provide strong evidences of predominant influence of the potassium-limitation, in addition to phosphorus limitation, on AM symbiosis with Capsicum in acidic soil at high altitude. We also conclude that the potassium should be considered in addition to carbon, nitrogen, and phosphorus in further studies investigating the stoichiometric relationships with the AMF symbioses in high altitude agro-ecosystems. PMID- 26555274 TI - Prehospital Administration of Epinephrine in Pediatric Anaphylaxis. AB - Anaphylaxis in the pediatric population is both serious and potentially lethal. The incidence of allergic and anaphylactic reactions has been increasing and the need for life saving intervention with epinephrine must remain an important part of Emergency Medical Services (EMS) provider training. Our aim was to characterize dosing and timing of epinephrine, diphenhydramine, and albuterol in the pediatric patient with anaphylaxis. In this retrospective chart review, we studied prehospital medication administration in pediatric patients ages 1 month up to 14 years old classified as having a severe allergic reaction or anaphylaxis. We compared rates of epinephrine, diphenhydramine, and albuterol given to patients with allergic conditions including anaphylaxis. In addition, we calculated the rate of epinephrine administration in cases of anaphylaxis and determined what percentage of time the epinephrine was given by EMS or prior to their arrival. Of the pediatric patient contacts, 205 were treated for allergic complaints. Of those with allergic complaints, 98 of 205 (48%; 95% CI 41%, 55%) had symptoms consistent with anaphylaxis and indications for epinephrine. Of these 98, 53 (54%, 95% CI 44%, 64%) were given epinephrine by EMS or prior to EMS arrival. Among the patients in anaphylaxis not given epinephrine prior to EMS arrival, 6 (12%; 95% CI 3%, 21%) received epinephrine from EMS, 10 (20%; 95% CI 9%, 30%) received diphenhydramine only, 9 (18%, 95% CI 7%-28%) received only albuterol and 17 (33%, 95% CI 20%-46%) received both albuterol and diphenhydramine. 9 patients in anaphylaxis received no treatment prior to arriving to the emergency department (18%, 95% CI 7%-28%). In pediatric patients who met criteria for anaphylaxis and the use of epinephrine, only 54% received epinephrine and the overwhelming majority received it prior to EMS arrival. EMS personnel may not be treating anaphylaxis appropriately with epinephrine. PMID- 26555276 TI - Culturing Mouse Cardiac Valves in the Miniature Tissue Culture System. AB - Heart valve disease is a major burden in the Western world and no effective treatment is available. This is mainly due to a lack of knowledge of the molecular, cellular and mechanical mechanisms underlying the maintenance and/or loss of the valvular structure. Current models used to study valvular biology include in vitro cultures of valvular endothelial and interstitial cells. Although, in vitro culturing models provide both cellular and molecular mechanisms, the mechanisms involved in the 3D-organization of the valve remain unclear. While in vivo models have provided insight into the molecular mechanisms underlying valvular development, insight into adult valvular biology is still elusive. In order to be able to study the regulation of the valvular 3D organization on tissue, cellular and molecular levels, we have developed the Miniature Tissue Culture System. In this ex vivo flow model the mitral or the aortic valve is cultured in its natural position in the heart. The natural configuration and composition of the leaflet are maintained allowing the most natural response of the valvular cells to stimuli. The valves remain viable and are responsive to changing environmental conditions. This MTCS may provide advantages on studying questions including but not limited to, how does the 3D organization affect valvular biology, what factors affect 3D organization of the valve, and which network of signaling pathways regulates the 3D organization of the valve. PMID- 26555275 TI - With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies. AB - The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with beta actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies. PMID- 26555277 TI - Women at the Podium: ACNP Strives to Reach Speaker Gender Equality at the Annual Meeting. PMID- 26555278 TI - Circumspectives: Cannabis and Psychiatric Illness: Blunt Thoughts. PMID- 26555279 TI - 4D microvascular imaging based on ultrafast Doppler tomography. AB - 4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 MUm * 100 MUm * 500 MUm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 MUm * 100 MUm * 100 MUm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment. PMID- 26555280 TI - The Pre-rRNA Processing Complex in Arabidopsis Includes Two WD40-Domain Containing Proteins Encoded by Glucose-Inducible Genes and Plant-Specific Proteins. PMID- 26555283 TI - Pigmented purpuric dermatosis after taking a dietary supplement. AB - Pigmented purpuric dermatoses (PPDs) are a group of histologically similar skin eruptions characterized by a perivascular lymphocytic infiltrate with extravasated erythrocytes. The etiologies of these conditions are unknown, but triggering factors such as systemic diseases, infections, drugs, and foods have been described. Here, we present a patient who developed pigmented purpura 30 days after initiating a dietary supplement that contained selenium, natural vitamin E, and a parsley concentrate, specifically, Parselenium E. One month after stopping the dietary supplement, the lesions disappeared and no new lesions have developed. PMID- 26555281 TI - Plants and climate change: complexities and surprises. AB - BACKGROUND: Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant-climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. SCOPE: We reviewed the literature on species' responses to ACC, finding ~42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant plant and plant-herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. CONCLUSIONS: We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man made. PMID- 26555284 TI - Labial salivary gland biopsy for diagnosing immunoglobulin light chain amyloidosis: a retrospective analysis. AB - Our goal was to evaluate the usefulness of labial salivary gland (LSG) biopsy for diagnosing immunoglobulin light chain (AL) amyloidosis, by comparing bone marrow and skin biopsies in the same patient population. This retrospective study included 34 consecutive patients who showed evidence of monoclonal proteins and symptoms considered to be due to amyloidosis, and who underwent a tissue biopsy from LSG between January 2005 and December 2012 at Nagoya City University Hospital. All samples of superficial tissues, including LSG, bone marrow, and skin, were independently evaluated as having amyloid deposits by a central review, which was blind to clinical information. An AL amyloidosis diagnosis was based on evidence of amyloid deposition in any biopsied tissue. Eighteen patients were diagnosed with AL amyloidosis. The sensitivity for detecting amyloid deposition was highest in biopsies of LSG at 89 %, followed by 77 % for bone marrow, and 72 % for skin. Amyloid deposition was detected in at least one superficial tissue of all the 18 patients. An LSG biopsy may be appropriate as a first-choice procedure to diagnose AL amyloidosis. Multiple biopsies of superficial tissues, including LSG, bone marrow, and skin, are recommended to increase the sensitivity for diagnosing AL amyloidosis. PMID- 26555285 TI - Detection of BCR-ABL1 mutations that confer tyrosine kinase inhibitor resistance using massively parallel, next generation sequencing. AB - Detection of BCR-ABL1 mutations that confer resistance to tyrosine kinase inhibitors is important for management of patients with t(9;22);BCR-ABL1-positive (Ph+) leukemias. Testing is often performed using Sanger sequencing (SS) which has relatively poor sensitivity. Given the widespread adoption of next generation sequencing (NGS), we sought to reevaluate the testing in the context of NGS methods. We developed an NGS-based BCR-ABL1 mutation test on the Ion Torrent Personal Genome Machine (PGM) to test for resistance mutations, primarily in the kinase domain in BCR-ABL1. We analyzed 508 clinical samples from patients with Ph+ leukemias. In a subset of these samples (n = 97), we conducted a comparison of the NGS results to a classical SS-based test. NGS facilitated detection of low level mutations (<20 % allele frequency) that were not detectable by SS. In a subset of cases with multiple mutations, NGS was also able to determine if two mutations were on the same molecule (compound) or on separate molecules (polyclonal) but this was limited by the distance between mutated positions and by the effects of apparent distance-dependent PCR recombination. We found 22 compound mutations that centered on one or two key residues including two novel compound mutants: Q252H/Y253H and F311Y/F359I. The advantages of NGS make it a superior method for inventorying BCR-ABL1 resistance mutations. However, data analysis may be complicated by short read lengths and the effects of PCR recombination. PMID- 26555286 TI - LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance. AB - The nonhematopoietic bone marrow (BM) microenvironment provides a functional niche for hematopoietic cell maintenance, recruitment, and differentiation. It consists of multiple cell types including vasculature, bone, adipose tissue, and fibroblast-like bone marrow stromal cells (BMSC), which can be summarized under the generic term niche cells. BMSC express Toll-like receptors (TLRs) and are capable to respond to TLR-agonists by changing their cytokine expression pattern in order to more efficiently support hematopoiesis. Here, we show that in addition to enhanced myeloid colony formation from human CD34+ cells, lipopolysaccharide (LPS) stimulation retains overall higher numbers of CD34+ cells in co-culture assays using BMSC, with eightfold more CD34+ cells that underwent up to three divisions as compared to non-stimulated assays. When subjected to cytokine-supplemented myeloid colony-forming unit (CFU) assays or transplanted into newborn RAG2(-/-) gammac (-/-) mice, CD34(+) cells from LPS stimulated BMSC cultures give rise to the full spectrum of myeloid colonies and T and B cells, respectively, thus supporting maintenance of myeloid and lymphoid primed hematopoietic progenitor cells (HPCs) under inflammatory conditions. Collectively, we suggest that BMSC enhance hematopoiesis during inflammatory conditions to support the replenishment of innate immune effector cells and to prevent the exhaustion of the hematopoietic stem and progenitor cell (HSPC) pool. PMID- 26555287 TI - Selective sweeps versus introgression - population genetic dynamics of the murine leukemia virus receptor Xpr1 in wild populations of the house mouse (Mus musculus). AB - BACKGROUND: The interaction between viruses and their receptors in the host can be expected to lead to an evolutionary arms race resulting in cycles of rapid adaptations. We focus here on the receptor gene Xpr1 (xenotropic and polytropic retrovirus receptor 1) for murine leukemia viruses (MLVs). In a previous screen for selective sweeps in mouse populations we discovered that a population from Germany was almost monomorphic for Xpr1 haplotypes, while a population from France was polymorphic. RESULTS: Here we analyze Xpr1 sequences and haplotypes from a broad sample of wild mouse populations of two subspecies, M. m. domesticus and M. m. musculus, to trace the origins of this distinctive polymorphism pattern. We show that the high polymorphism in the population in France is caused by a relatively recent invasion of a haplotype from a population in Iran, rather than a selective sweep in Germany. The invading haplotype codes for a novel receptor variant, which has itself undergone a recent selective sweep in the Iranian population. CONCLUSIONS: Our data support a scenario in which Xpr1 is frequently subject to positive selection, possibly as a response to resistance development against recurrently emerging infectious viruses. During such an infection cycle, receptor variants that may convey viral resistance can be captured from another population and quickly introgress into populations actively dealing with the infectious virus. PMID- 26555288 TI - Implications of Volume Exclusion: A Look at Thermodynamic Perspective of DNA Hemoglobin Complexes and Their Reconstitutes Under Macromolecular Crowding. AB - Live cells contain high concentrations of macromolecules, but almost all experimental biochemical data have been generated from dilute solutions that do not reflect conditions in vivo. To understand biomolecular behavior in vivo, properties studied in vitro are extrapolated to conditions in vivo. Another significant factor which is overlooked is the effects of macromolecular crowding and its consequences in the actual biochemical and physiological environment. Such influences of crowding, its modification and physiological parameters have been reported. The present study investigates the effect of molecular crowding on binding characteristics of Salmon sperm DNA with Bovine hemoglobin and their reconstitutes in presence of molecular crowders viz., Poly ethylene glycol (PEG) and Dextran of different molecular weight by fluorescence, UV visible spectroscopic technique at different temperatures. The results showed that BHb fluorescence was quenched by sDNA through static quenching mechanism which is enhanced in presence of polymers. The number of binding sites 'n' and binding constants 'K' were determined at different temperatures based on fluorescence quenching. The thermodynamic parameters namely ?H degrees , ?G degrees , T?S degrees were studied at different temperatures and the results indicate that hydrophobic forces are predominant in the sDNA-BHb complex. Negative ?G degrees values imply that the binding process is spontaneous. PMID- 26555289 TI - Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes. AB - The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5 (methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10 Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1 phase. PMID- 26555290 TI - Two Sensitive Fluorescent BOPIM Probes with Tunable TICT Character for Low-Level Water Detection in Organic Solvents. AB - Two novel Boron-fluorine derivatives bearing dimethylamino moieties, BOPIM-1 and BOPIM-2, were proposed as sensitive fluorescent sensors for low-level water quantification in organic solvents. Two BOPIMs exhibit typical phenomenon for an emission from a twisted intra-molecular charge transfer (TICT) state, the emission red shift and intensity weakening with solvent polarity. Introduction of trace amount of water to solvent resulted in fluorescent quenching, accompanied by the red shift of the emission, which was attributed to the formation of TICT excitation of BOPIMs by hydrolysis. A quantification method to detect water content was developed, described by a linear equation lg(I/I(0)) vs. lg phi(w) in the range of phi(w) (volume fraction of water) 0.001~0.01, 0.01~0.1, respectively. The experiment results of determination of water in real 1, 4 dioxane (Diox) samples proved that this method can be used in practical application. PMID- 26555291 TI - Synthesis, Characterization, Properties and DFT Calculations of 2 (Benzo[b]thiophen-2-yl)pyridine-based Iridium(III) Complexes with Different Ancillary Ligands. AB - A series of new cyclometalated btp-based iridium(III) complexes with three different ancillary ligands, Ir(btp)2(bozp) (3a), Ir(btp)2(btzp) (3b) and Ir(btp)2(izp) (3c) (btp = 2-(benzo[b]thiophen-2-yl)pyridine, bozp =2 (benzo[d]oxazol-2-yl)phenol, btzp =2-(benzo[d]thiazol-2-yl)phenol, izp = 2-(2 H indazol-2-yl)phenol), have been synthesized and fully characterized. The crystal structure of 3b has been determined by single crystal X-ray diffraction analysis. A comparative study has been carried out for complexes 3a - 3c by UV-vis absorption spectroscopy, photoluminescence spectroscopy, cyclic voltammetry and DFT calculations. This observation illustrates that the substitution of N or S in ancillary ligand can lead to a marked bathochromic shift of absorption and emission wavelengths. The spectroscopic characterisation of these complexes has been complemented by DFT and TD-DFT calculations, supporting the assignment of (3)MLCT/(3)LC to the lowest energy excited state. PMID- 26555292 TI - Impaired cardiac PET image quality due to delayed (82)Rubidium dose delivery to the heart. PMID- 26555293 TI - Moving ahead with CZT technology. PMID- 26555294 TI - Rusa alfredi papillomavirus 1 - a novel deltapapillomavirus inducing endemic papillomatosis in the endangered Visayan spotted deer. AB - We describe a novel papillomavirus - Rusa alfredi papillomavirus 1 (RalPV1) - which causes endemic fibropapillomatosis in the European conservation breeding population of the highly endangered Visayan spotted deer (Rusa alfredi). Degenerated papillomavirus-specific primers were used to amplify and sequence parts of the viral DNA. Subsequently, the complete genomic DNA was cloned and the sequence was determined. The RalPV1 genome has a length of 8029 bp, encodes the early proteins E6, E7, E1, E2 and E5, the two late proteins L1 and L2 and contains an upstream regulatory region. Highest sequence identities were observed with two deltapapillomaviruses, the Capreolus capreolus PV1 and Cervus elaphus PV1. Pairwise comparisons and phylogenetic analysis based on the ORF L1 suggested that RalPV1 is a putative new type of the papillomavirus species Deltapapillomavirus 5. PMID- 26555295 TI - Erratum to: Vitamin D regulating TGF-beta induced epithelial-mesenchymal transition. PMID- 26555297 TI - Analytical approaches for lipidomics and its potential applications in neuropsychiatric disorders. AB - OBJECTIVES: In this review, the authors discuss an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical techniques and clinical research in neuropsychiatric disorders. METHODS: Lipidomics is a lipid targeted metabolomics approach aiming at the comprehensive analysis of lipids in biological systems. Recent technological advancements in mass spectrometry and chromatography have greatly enhanced the development and applications of metabolic profiling of diverse lipids in complex biological samples. RESULTS: An effective evaluation of the clinical course of diseases requires the application of very precise diagnostic and assessment approaches as early as possible. In order to achieve this, "omics" strategies offer new opportunities for biomarker identification and/or discovery in complex diseases and may provide pathological pathways understanding for diseases beyond traditional methodologies. CONCLUSIONS: This review highlights the importance of lipidomics for the future perspectives as a tool for biomarker identification and discovery and its clinical application. PMID- 26555298 TI - Metastatic periampullary clear cell renal carcinoma. PMID- 26555296 TI - Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas. AB - BACKGROUND: USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. METHODS: Heterozygous USP18 +/- FVB/N mice were bred to generate wild type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. RESULTS: USP18 -/- FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6-12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly decreased time to metastasis (P = 0.0441). CONCLUSIONS: USP18 null mice develop leiomyosarcoma recapitulating key features of clinical leiomyosarcomas and patients with reduced-USP18 tumor levels have an unfavorable outcome. USP18 null mice and the derived cell lines represent clinically-relevant models of leiomyosarcoma and can provide insights into both leiomyosarcoma biology and therapy. PMID- 26555299 TI - Melanosis coli: a disappearing act. PMID- 26555300 TI - Novel covered pancreatic metal stents for the treatment of bleeding after endoscopic pancreatic sphincterotomy. PMID- 26555301 TI - Dual anti-inflammatory and selective inhibition mechanism of leukotriene A4 hydrolase/aminopeptidase: insights from comparative molecular dynamics and binding free energy analyses. AB - Human leukotriene A4 hydrolase/aminopeptidase (LTA4H) is a zinc metalloenzyme with a dual catalytic activity; conversion of LTA4 into LTB4 and degradation of chemotactic tripeptide Pro-Gly-Pro (PGP). Existing inhibitors, such as SC-57461A, block both catalytic activities of the enzyme, leading to drug failures. Recently, a novel compound, ARM1, was reported to selectively inhibit the hydrolase activity of LTA4H while sparing its aminopeptidase activity. However, the molecular understanding of such preferential inhibitory mechanism remains obscure. The discovery of ARM1 prompted us to further explore its binding theme and provide more insight into the structural and dual mechanistic features of LTA4H protein. To accomplish this, we embarked on wide range of computational tools, including comparative molecular dynamics (MDs) simulations and postdynamic analyses for LTA4H and in complex with ARM1, PGP, ARM1-PGP, and SC-57461A. MD analysis reveals that the binding of ARM1 exhibits a more stable active site and overall stable protein conformation when compared to the nonselective inhibitor SC-57461A. In addition, MM/GBSA-binding free energy calculation also reveals that ARM1 exhibit a lower binding affinity, when compared to the nonselective inhibitor SC-57461A - which is in a great agreement with experimental data. Per residue energy decomposition analysis showed that Phe314, Val367, Tyr378, Trp311, Pro382, and Leu369 are key residues critical for the selective inhibition of the epoxide hydrolase activity of LTA4H by ARM1. Findings from this report will not only provide more understanding into the structural, dynamic, and mechanistic features of LTA4H but would also assist toward the rational design of novel and selective hydrolase inhibitors of LTA4H as anti-inflammatory drugs. PMID- 26555302 TI - Cytotoxic T lymphocyte antigen 4 decreases humoral and cellular immunity by adenovirus to enhance target GFP gene transfer in C57BL/6 mice. AB - Adenoviruses (Ad) are once potential and promising vectors for gene delivery, but the immunogenicity attenuates its transfer efficiency. Cytotoxic T lymphocyte antigen 4 (CTLA-4) can inhibit T cell immunity. Thus, we aimed to study the effect of CTLA-4 in the process of Ad-mediated gene transfer. The C57BL/6 mice were injected by Ad vectors at twice, and CTLA-4 was administrated after the first Ad injection. Then, the CD3(+)CD4(+) T cells and circulating levels of IL 2, IL-4, and anti-Ad IgG were decreased by CTLA-4, while Ad generated immune responses. The green fluorescence protein (GFP) expressions of tissues were enhanced by CTLA-4 till injection of Ad at twice. Our results indicate that CTLA 4 can inhibit humoral and cellular immunity by adenovirus generation to enhance GFP delivery, and provide a potential way to assist in Ad-mediated gene transfer. PMID- 26555303 TI - Evaluation of an automated knowledge based treatment planning system for head and neck. AB - BACKGROUND: This study evaluated an automated inverse treatment planning algorithm, Pinnacle Auto-Planning (AP), and compared automatically generated plans with historical plans in a large cohort of head and neck cancer patients. METHODS: Fifty consecutive patients treated with volumetric modulated arc therapy (Eclipse, Varian Medical System, Palo Alto, CA) for head and neck were re-planned with AP version 9.10. Only one single cycle of plan optimization using one single template was allowed for AP. The dose to the planning target volumes (PTV's; 3-4 dose levels), the organs at risk (OAR's) and the effective working time for planning was evaluated. Additionally, two experienced radiation oncologists blind reviewed and ranked 10 plans. RESULTS: Dose coverage and dose homogeneity of the PTV were significantly improved with AP, however manually optimized plans showed significantly improved dose conformity. The mean dose to the parotid glands, oral mucosa, swallowing muscles, dorsal neck tissue and maximal dose to the spinal cord were significantly reduced with AP. In 64 % of the plans, the mean dose to any OAR (spinal cord excluded) was reduced by >20 % with AP in comparison to the manually optimized plans. In 12 % of the plans, the manually optimized plans showed reduced doses by >20 % in at least one OAR. The experienced radiation oncologists preferred the AP plan and the clinical plan in 80 and 20 % of the cases, respectively. The average effective working time was 3.8 min +/- 1.1 min in comparison to 48.5 min +/- 6.0 min using AP compared to the manually optimized plans, respectively. CONCLUSION: The evaluated automated planning algorithm achieved highly consistent and significantly improved treatment plans with potentially clinically relevant OAR sparing by >20 % in 64 % of the cases. The effective working time was substantially reduced with Auto-Planning. PMID- 26555304 TI - Mid-Infrared Spectroscopy Analysis of the Effects of Erbium, Chromium:Yattrium Scandium-Gallium-Garnet (Er,Cr:YSGG) Laser Irradiation on Bone Mineral and Organic Components. AB - The effects of varying the energy density of a high-intensity erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser on the mineral and organic components of bone tissue were evaluated using Fourier transform infrared spectroscopy. Bone samples obtained from the tibias of rabbits were irradiated with five energy densities (3, 6, 8, 12, and 15 J/cm(2)), and the effects on the carbonate to phosphate ratio and in the organic components were compared with those of nonirradiated samples. The increased temperature during the laser irradiation was also measured using infrared thermography to relate the observed spectral changes to the laser thermal effects. The analyses of the infrared spectra suggests that the irradiation with Er,Cr:YSGG promoted changes in bone tissue in both the mineral and organic components that depend on the laser energy density, pointing to the importance of using the proper energy density in clinical procedures. PMID- 26555305 TI - Pediatric Erythema Multiforme in the Emergency Department: More Than "Just a Rash". AB - OBJECTIVES: Erythema multiforme (EM) is characterized by symmetrical acrally distributed target lesions; however, other conditions can mimic the clinical features of EM. Although it is typically self-limiting, alternative diagnoses may be life-threatening and require immediate identification and treatment. This study aimed to investigate the clinical spectrum and accuracy of diagnosis of pediatric EM in the emergency department (ED). METHODS: A retrospective, descriptive study of all pediatric patients with an ED information system diagnosis of EM at 2 EDs in Southeast Queensland between January 2010 and July 2013. Cases were evaluated using previously established EM classification criteria. RESULTS: Seventy patients (34 males and 36 females) with a diagnosis of EM were identified. From 57 cases where a diagnosis could be established, 9 cases fulfilled the classification criteria for EM. No patients had mucosal involvement, and therefore, all 9 cases were classified as EM minor, with the majority (89%) attributed to viral infection. Of the 48 cases that did not fit the criteria, the most common condition misdiagnosed as EM was urticaria multiforme (n = 20). CONCLUSIONS: In the ED setting, EM in children is frequently misdiagnosed. Greater awareness of diagnostic factors for EM may improve diagnostic accuracy. Teledermatology and incentives to include clinical pictures in the (electronic) medical record may be useful adjuncts for patients with suspected EM and other dermatological conditions. PMID- 26555306 TI - Medulloblastoma With Obstructive Hydrocephalus in a Young Infant. AB - Medulloblastoma is the most common posterior fossa tumor diagnosed in young infants. The presentation of posterior fossa tumors in neonates is highly variable. We report the case of a 2-month-old child who presented with poor feeding and lethargy and was noted to have a fixed downward gaze. Head computed tomography revealed a posterior fossa mass that was pathologically consistent with a medulloblastoma. This case demonstrates the uncommon presentation of posterior fossa tumors in young infants. PMID- 26555307 TI - Management of Pediatric Forearm Torus Fractures: A Systematic Review and Meta Analysis. AB - OBJECTIVES: Pediatric forearm torus fracture, a frequent reason for emergency department visits, can be immobilized by both rigid cast and nonrigid methods. However, controversy still exists regarding the optimal treatment of the disease. The aim of this study was to compare, in a systematic review, clinical efficacy of rigid cast with nonrigid methods for immobilization of the pediatric forearm torus fractures. METHODS: Literature search was performed of PubMed and Cochrane Library by 2 independent reviewers to identify randomized controlled trials comparing rigid cast with nonrigid methods for pediatric forearm torus fractures from inception to December 31, 2013, without limitation of publication language. Trial quality was assessed using the modified Jadad scale. RESULTS: Eight randomized controlled trials with a total of 781 participants met all inclusion criteria. The nonrigid methods for immobilization included soft cast, splint, bandage, and slab. Results showed that nonrigid immobilizations had better clinical efficacy than rigid cast regarding functional recovery, treatment cost, and complication rate (relative risk, 3.02; 95% confidence interval, 1.70-5.37; P = 0.0002). Compared with rigid cast, more patients would like to choose the nonrigid methods of immobilization for future use. However, discrepant results sill surrounds the pain levels of the patients. CONCLUSIONS: The current study suggests that the nonrigid immobilization methods have more advantages than rigid cast for immobilization of pediatric forearm torus fracture. The former strategies are also safe enough for clinical therapy. PMID- 26555308 TI - Human Immunodeficiency Virus Risk Factors and Beliefs Reported by Families Presenting to a Pediatric Emergency Department. AB - OBJECTIVES: Adolescents are at greater risk for acquiring human immunodeficiency virus (HIV) due to increased risk behaviors. Parental influence is known to reduce adolescent risk behaviors. We compared HIV risk behaviors reported by adolescents to parents' perception of adolescent risky behavior engagement. We also examined participants' knowledge of HIV transmission and testing preferences. METHODS: Participants included English-speaking adolescents and parents presenting to a pediatric emergency department. Participants were interviewed separately in private. Modeled after existing instruments, "adolescent" and "parent" questionnaires included multiple choices items, Likert type scales, and standard yes/no and true/false options. Data were analyzed using a kappa statistic and observed agreement to measure discordance between adolescent and parent responses. RESULTS: Participants included 126 adolescents and 110 parents. Many adolescents reported ever having sex (61%), of which 32% reported always practicing safe sex. Comparative analysis revealed low agreement between adolescents' risk behaviors and parents' perception of risk behavior engagement by youth. Discordance concerning tobacco use was greatest (kappa = 0.13), followed by drug use (kappa = 0.19) and ever having sex (kappa= 0.19), and alcohol use (kappa= 0.22). There was also poor agreement regarding HIV transmission knowledge (ie, oral sex; kappa = 0.16). Participants shared strong agreement regarding parental support for adolescent interest in HIV testing (95.5%). CONCLUSIONS: Parents are mostly unaware of adolescents' broad risk behaviors. Participants' knowledge of HIV transmission is limited. Adolescents and parents shared strong agreement regarding HIV testing preferences. Multidimensional HIV prevention strategies aiming to decrease adolescent risk behaviors, increase parental involvement, and improve adolescent and parental knowledge of HIV transmission are needed. PMID- 26555309 TI - Intussusception in Children Presenting to the Emergency Department: An Asian Perspective. AB - OBJECTIVE: This project examines the presenting complaints of children with intussusception in the emergency department in an Asian population, with a focus on older children, which has not been well described in previous studies. METHODS: A retrospective study was conducted on children aged 6 months to 15 years, whose conditions were diagnosed with intussusception in KK Women's and Children's Hospital for a 5-year period (2009-2013), based on the case definition established by the Brighton Collaborate Intussusception Working Group. RESULTS: Three hundred ninety-one cases were identified to fulfill the case definition as per the Brighton Collaborative Intussusception Working Group. The mean age of children diagnosed with intussusception is 2.59 years, predominantly in males (65.22%). A total of 3.33% were 10 years or older. Only 3.58% presented with the classical triad-intermittent abdominal pain, vomiting, and bloody stools. In contrast, 22.51% of our Asian patients presented with a triad of intermittent abdominal pain, indrawing of legs, and vomiting. A total of 76.73% of our subjects were treated by air enema only, whereas 22 required surgical treatment after unsuccessful attempts of air enema, and 63 resolved spontaneously, including 7 with ileoileal intussusception. No mortality was documented. CONCLUSIONS: Intussusception is usually diagnosed in the younger population (age <1 year) and predominantly in males. Our study has established that older Asian children can also have intussusception. The classical triad is not a very sensitive diagnostic tool, but the combination of abdominal pain, indrawing of legs, and vomiting may be a more common presenting triad in Asian children. PMID- 26555310 TI - Simultaneous Acquired Self-limited Hemophagocytic Lymphohistiocytosis and Kikuchi Necrotizing Lymphadenitis in a 16-Year-Old Teenage Girl: A Case Report and Review of the Literature. AB - OBJECTIVES: The aim of this study was to increase education and awareness among pediatric practitioners of possibility of simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease/Kikuchi disease occurring in the pediatric population and the diagnostic dilemma it can present. We describe a case presentation of acquired and self-limited simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease in a 16-year-old in the United States who presented with fevers, night sweats, and joint pain, along with tiredness and decreased appetite along with pancytopenia and elevated lactate dehydrogenase. To the best of our knowledge, simultaneous hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto in the pediatric population has not been described in North America but remains fairly common in Asia. The literature on both diseases and their simultaneous occurrence is comprehensively reviewed. METHODS: This was a case report and review of the literature. RESULTS: The patient was diagnosed with both hemophagocytic lymphohistiocytosis and Kikuchi Fujimoto disease based on bone marrow aspiration/biopsy and axillary node biopsy, respectively. Both illnesses resolved completely. CONCLUSIONS: Benign causes of pancytopenia and elevated lactate dehydrogenase exist, but they may not be always straightforward diagnostically. Bone marrow aspiration and lymph node biopsy may be helpful in ascertaining the diagnosis. Hemophagocytic lymphohistiocytosis and Kikuchi-Fujimoto disease may represent a continuum of illness. PMID- 26555311 TI - Antibiotic Prescribing Patterns Across the Continuum of Care for Children Hospitalized With Community-Acquired Pneumonia. AB - OBJECTIVES: The aim of this study was to describe the variation in antibiotic prescribing practices for uncomplicated community-acquired pneumonia across the continuum of care for hospitalized pediatric patients to better inform future efforts at standardizing antibiotic therapy throughout a single hospitalization. METHODS: This is a retrospective cohort study involving 4 hospitals caring for children aged 3 months to 18 years, hospitalized between January 1, 2011, and December 31, 2012, with diagnosis of uncomplicated pneumonia and without complex chronic medical conditions.Data collected include antibiotics prescribed before hospitalization, at the emergency department (ED) encounter, during hospitalization, and at hospital discharge. RESULTS: Six hundred nine children met inclusion criteria, with a mean age of 5.3 years and median length of stay of 2 days. Emergency department providers prescribed narrow-spectrum therapy 27% of the time, whereas discharging providers prescribed narrow-spectrum therapy 56% of the time. Third- and fourth-generation cephalosporins were less often prescribed in the preadmission setting and at discharge but were more often prescribed in the ED and inpatient setting. There was an association between inpatient prescription of broad-spectrum antibiotics when a blood culture was obtained, when broad-spectrum antibiotics were prescribed in the ED, and with increasing length of stay. CONCLUSION: Broad-spectrum antibiotic therapy for community acquired pneumonia, especially third- and fourth-generation cephalosporins, often originates in the ED. When initiated in this setting, it is likely to be continued in the inpatient setting. PMID- 26555312 TI - Television-Related Head Injuries in Children: A Secondary Analysis of a Large Cohort Study of Head-Injured Children in the Pediatric Emergency Care Applied Research Network. AB - OBJECTIVE: The objective of the study was to describe the epidemiology, cranial computed tomography (CT) findings, and clinical outcomes of children with blunt head trauma after television tip-over injuries. METHODS: We performed a secondary analysis of children younger than 18 years prospectively evaluated for blunt head trauma at 25 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from June 2004 to September 2006. Children injured from falling televisions were included. Patients were excluded if injuries occurred more than 24 hours before ED evaluation or if neuroimaging was obtained before evaluation. Data collected included age, race, sex, cranial CT findings, and clinical outcomes. Clinically important traumatic brain injuries (ciTBIs) were defined as death from TBI, neurosurgery, intubation for more than 24 hours for the TBI, or hospital admission of 2 nights or more for the head injury, in association with TBI on CT. RESULTS: A total of 43,904 children were enrolled into the primary study and 218 (0.5%; 95% confidence interval [CI], 0.4% to 0.6%) were struck by falling televisions. The median (interquartile range) age of the 218 patients was 3.1 (1.9-4.9) years. Seventy-five (34%) of the 218 underwent CT scanning. Ten (13.3%; 95% CI, 6.6% to 23.2%) of the 75 patients with an ED CT had traumatic findings on cranial CT scan. Six patients met the criteria for ciTBI. Three of these patients died. All 6 patients with ciTBIs were younger than 5 years. CONCLUSIONS: Television tip-overs may cause ciTBIs in children, including death, and the most severe injuries occur in children 5 years or younger. These injuries may be preventable by simple preventive measures such as anchoring television sets with straps. PMID- 26555313 TI - A push-button: Spodoptera exigua oviposition on Nicotiana attenuata dose independently primes the feeding-induced plant defense. AB - Insect oviposition on a plant often precedes the attack by herbivorous larvae. We recently discovered that oviposition by Spodoptera exigua moths on the desert tobacco Nicotiana attenuata primes the induction of 2 defense traits, a phenylpropanoid and activity of protease inhibitors, in response to larval feeding. Oviposition-experienced plants suffer a reduced feeding damage by less and smaller larvae than unexperienced control plants. The increased resistance of oviposition-experienced plants requires the plant's ability to activate its biosynthesis of phenylpropanoids via a Myb transcription factor. Oviposition by S. exigua on N. attenuata is highly variable with respect to the amount, distribution and localization of the eggs on the plant. This raises the question, whether the plant's priming of herbivore defense depends on the egg number and localization. S. exigua moths prefer the oldest leaves for oviposition and yet prime defense-induction in the larval attacked young systemic leaves. Neither the levels of the primed defense traits, nor the affected larval mortality correlate with the number of eggs a plant previously received. This suggests that upon S. exigua oviposition, N. attenuata is shifted - independently of the egg-dose - into a primed state that is responding stronger to the feeding larvae than unprimed plants. PMID- 26555314 TI - Characterization of Perovskite Obtained from Two-Step Deposition on Mesoporous Titania. AB - The properties of perovskite films are sensitive to the fabrication method, which plays a crucial role in the performance of perovskite solar cell. In this work, we fabricate organo-lead iodide perovskite on mesoporous TiO2 films through two different two-step deposition methods, respectively, for the purpose of studying the crystal growth of perovskite film and its effect on light harvesting efficiency, defect density, charge extraction rate, and energy levels. The crystal growth exerts a significant influence on the morphology and hence the film properties, which are found to correlate with the performance of solar cells. It is found that vapor deposition of methylammonium iodide in the PbI2 lattice gives a more complete coverage on mesoporous TiO2 with a flatter surface and Fermi level closer to the middle of the band-gap, resulting in higher light absorption in the visible spectral region, lower defect density, and faster charge extraction, as compared to the sequential solution deposition. For this reason, the vapor-processed perovskite film achieves higher short-circuit photocurrent and power conversion efficiency than the solution-processed film. PMID- 26555315 TI - Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease. AB - INTRODUCTION: Stress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models. METHODS: To test whether antagonism of the type-1 corticotropin-releasing factor receptor (CRFR1) could be used as a disease modifying treatment for AD, we used a preclinical prevention paradigm and treated 30-day-old AD transgenic mice with the small-molecule, CRFR1-selective antagonist, R121919, for 5 months, and examined AD pathologic and behavioral end points. RESULTS: R121919 significantly prevented the onset of cognitive impairment in female mice and reduced cellular and synaptic deficits and beta amyloid and C-terminal fragment-beta levels in both genders. We observed no tolerability or toxicity issues in mice treated with R121919. DISCUSSION: CRFR1 antagonism presents a viable disease-modifying therapy for AD, recommending its advancement to early-phase human safety trials. PMID- 26555316 TI - Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of beta-amyloid (1-42) in human cerebrospinal fluid. AB - INTRODUCTION: Available assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid-beta 1-42 (Abeta [1-42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys beta-amyloid (1-42) assay (Roche Diagnostics). METHODS: Lot-to-lot comparability was tested using method comparison. Performance parameters were measured according to Clinical & Laboratory Standards Institute (CLSI) guidelines. The assay was standardized to a Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved RMP. RESULTS: Limit of quantitation was <11.28 pg/mL, and the assay was linear throughout the measuring range (200-1700 pg/mL). Excellent lot-to-lot comparability was observed (correlation coefficients [Pearson's r] >0.995; bias in medical decision area <2%). Repeatability coefficients of variation (CVs) were 1.0%-1.6%, intermediate CVs were 1.9%-4.0%, and intermodule CVs were 1.1%-3.9%. Estimated total reproducibility was 2.0% 5.1%. Correlation with the RMP was good (Pearson's r, 0.93). DISCUSSION: The Elecsys beta-amyloid (1-42) assay has high analytical performance that may improve biomarker-based AD diagnosis. PMID- 26555317 TI - Can the use of natural biostimulants be a potential means of phytoremediating contaminated soils from goldmines in South Africa? AB - Biostimulants offer great potential in improving phytoremediation of contaminated soils. In the current greenhouse-based study, Brassica juncea seedlings grown on soils collected from Krugersdorp Goldmine and the adjourning areas (a Game Reserve and private farmland) were supplemented with different biostimulants (Kelpak(r) = KEL, vermicompost leachate = VCL, smoke-water = SW). Indole-3 butyric acid (IBA) was included in the study for comparative purposes because these biostimulants are known to enhance rooting. Prior to the pot trial, concentrations of elements in the three soil types were determined using Inductively Coupled Plasma-Optical Emission Spectroscopy. Plants were harvested after 105 days and the growth and concentrations of elements in the various plant organs were determined. TheB. juncea seedlings with and without biostimulants did not survive when growing in soil from the Krugersdorp Goldmine. The Game Reserve and private farmland soils supplemented with KEL produced the highest plant biomass and the lowest accumulation of metals in the organs of B. juncea. High concentrations (>13 000 mg kg(-1)) of zinc and aluminium were quantified in the roots of IBA-supplemented soils from the Game Reserve. Generally, IBA and SW enhanced the phytoremediation of B. juncea due to elevated levels of elements that accumulated in their different organs. PMID- 26555318 TI - Folding Up of Gold Nanoparticle Strings into Plasmonic Vesicles for Enhanced Photoacoustic Imaging. AB - The stepwise self-assembly of hollow plasmonic vesicles with vesicular membranes containing strings of gold nanoparticles (NPs) is reported. The formation of chain vesicles can be controlled by tuning the density of the polymer ligands on the surface of the gold NPs. The strong absorption of the chain vesicles in the near-infrared (NIR) region leads to a much higher efficiency in photoacoustic (PA) imaging than for non-chain vesicles. The chain vesicles were further employed for the encapsulation of drugs and the NIR light triggered release of payloads. This work not only offers a new platform for controlling the hierarchical self-assembly of NPs, but also demonstrates that the physical properties of the materials can be tailored by controlling the spatial arrangement of NPs within assemblies to achieve a better performance in biomedical applications. PMID- 26555319 TI - Link Between Foot Pain Severity and Prevalence of Depressive Symptoms. AB - OBJECTIVE: Associations between pain and depression are well known, yet foot pain, common in populations, has been understudied. This cross-sectional study examined foot pain and severity of foot pain with depressive symptoms in adults. METHODS: Framingham Foot Study (2002-2008) participants completed questionnaires that included questions about foot pain (yes/no; none, mild, moderate, or severe pain) and the Center for Epidemiologic Studies Depression Scale (scores >=16 indicated depressive symptoms). Age and body mass index (BMI) were also assessed. Sex-specific logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations of foot pain with depressive symptoms, adjusting for age and BMI. In a subset, further models adjusted for leg pain, back pain, or other joint pain. RESULTS: Of 1,464 men and 1,857 women, the mean +/- SD age was 66 +/- 10 years. Depressive symptoms were reported in 21% of men and 27% of women. Compared to those with no foot pain and independent of age and BMI, both men and women with moderate foot pain had approximately a 2-fold increased odds of depressive symptoms (men with severe foot pain OR of 4 [95% CI 2.26-8.48], women with severe foot pain OR of 3 [95% CI 2.02-4.68]). Considering other pain regions attenuated ORs, but the pattern of results remained unchanged. CONCLUSION: Even after we adjusted for age, BMI, and other regions of pain, those reporting worse foot pain were more likely to report depressive symptoms. These findings suggest that foot pain may be a part of a broader pain spectrum, with an impact beyond localized pain and discomfort. PMID- 26555320 TI - Dispersal, dormancy and life-history tradeoffs at the individual, population and species levels in southern African Asteraceae. AB - Dispersal and dormancy are important risk-reducing strategies in unpredictable environments. Negative covariation between these strategies is theoretically expected, but empirical evidence is limited and inconsistent. Moreover, covariation may be affected by other life-history traits and may vary across levels of biological organization. We assessed dispersal (vertical fall time of fruits, a proxy for wind dispersal ability) and dormancy (germination fractions measured during germination trials) in populations of 15 annual and 12 perennial wind-dispersed species in six Asteraceae genera from South Africa. Dormancy was higher in annuals than in perennials, whereas fall time was largely determined by evolutionary history. Controlling for phylogeny, dispersal and dormancy was negatively associated across species and life-history categories. Negative covariation between dispersal and dormancy was not evident at either the individual level (except for seed heteromorphic species) or the population level. Our study provides rare empirical support for the theoretical expectation of tradeoffs between dormancy and the alternative risk-reducing strategies, perenniality and dispersal, but refutes the expectation of increased dispersability in perennials. Although negative covariation between dispersal and dormancy at the species level appears not to be a simple consequence of upscaling individual-level mechanistic tradeoffs, our findings suggest that selection for one strategy may constrain evolution of the other. PMID- 26555321 TI - Regarding "Compared Efficacy of Preservation Solutions in Liver Transplantation: A Long-Term Graft Outcome Study From the European Liver Transplant Registry". PMID- 26555322 TI - A large infrapatellar fat pad protects against knee pain and lateral tibial cartilage volume loss. AB - INTRODUCTION: The infrapatellar fat pad (IPFP) is commonly resected during knee joint arthroplasty, but the ramifications of doing so are unclear. This longitudinal study determined whether the size of the IPFP (maximum cross sectional area (CSA)) was associated with knee cartilage loss and the development of knee pain in adults without knee osteoarthritis (OA). METHODS: A total of 297 adults without American College of Rheumatology clinical criteria for a diagnosis of knee OA were recruited. Knee MRI was performed at baseline and an average of 2.3 years later. IPFP maximal CSA and tibial cartilage volume were measured from MRI. A large and small IPFP were defined by the median split, with a large IPFP defined by being in the highest 50%. Body composition was performed at baseline using bio-impedance. Knee pain was assessed at follow-up using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). RESULTS: A larger IPFP at baseline was associated with reduced knee pain at follow-up (OR 0.5, 95% CI: 0.3 to 0.9, p = 0.02) and lateral tibial cartilage volume loss (beta: -0.9% (95% CI: -1.6, -0.1%) per annum, p = 0.03). The maximal CSA of the IPFP was predominantly located in the lateral (54.2%), rather than the medial tibiofemoral compartment (1.7%). Male gender (OR 12.0, 95% CI: 6.5 to 22.0, p < 0.001) and fat free mass (OR 1.15, 95% CI 1.04 to 1.28, p = 0.007) were both associated with a large IPFP. CONCLUSION: A larger IPFP predicts reduced lateral tibial cartilage volume loss and development of knee pain and mechanistically might function as a local shock-absorber. The lack of association between measures of adiposity and the size of the IPFP might suggest that the IPFP size is not simply a marker of systemic obesity. PMID- 26555323 TI - Compressed sensing electron tomography of needle-shaped biological specimens- Potential for improved reconstruction fidelity with reduced dose. AB - Electron tomography is an invaluable method for 3D cellular imaging. The technique is, however, limited by the specimen geometry, with a loss of resolution due to a restricted tilt range, an increase in specimen thickness with tilt, and a resultant need for subjective and time-consuming manual segmentation. Here we show that 3D reconstructions of needle-shaped biological samples exhibit isotropic resolution, facilitating improved automated segmentation and feature detection. By using scanning transmission electron tomography, with small probe convergence angles, high spatial resolution is maintained over large depths of field and across the tilt range. Moreover, the application of compressed sensing methods to the needle data demonstrates how high fidelity reconstructions may be achieved with far fewer images (and thus greatly reduced dose) than needed by conventional methods. These findings open the door to high fidelity electron tomography over critically relevant length-scales, filling an important gap between existing 3D cellular imaging techniques. PMID- 26555324 TI - Simulation of the enhancement factor from an individual 3D hemisphere-on-post field emitter by using finite elements method. AB - This paper presents a 3D computational framework for evaluating electrostatic properties of a single field emitter characterized by the hemisphere-on-post geometry. Numerical simulations employed the finite elements method by using Ansys-Maxwell software. Extensive parametric simulations were focused on the threshold distance from which the emitter field enhancement factor (gamma) becomes independent from the anode-substrate gap (G). This investigation allowed demonstrating that the ratio between G and the emitter height (h) is a reliable reference for a broad range of emitter dimensions; furthermore, results permitted establishing G/h >= 2.2 as the threshold condition for setting the anode without affecting gamma. PMID- 26555325 TI - Theoretical estimates of spherical and chromatic aberration in photoemission electron microscopy. AB - We present theoretical estimates of the mean coefficients of spherical and chromatic aberration for low energy photoemission electron microscopy (PEEM). Using simple analytic models, we find that the aberration coefficients depend primarily on the difference between the photon energy and the photoemission threshold, as expected. However, the shape of the photoelectron spectral distribution impacts the coefficients by up to 30%. These estimates should allow more precise correction of aberration in PEEM in experimental situations where the aberration coefficients and precise electron energy distribution cannot be readily measured. PMID- 26555326 TI - Weight Loss, The Obesity Paradox in Rheumatoid Arthritis: Is It a Paradox? Comment on the Article by Baker et al. PMID- 26555327 TI - Going the Distance: Colorectal Cancer Screening in Women. PMID- 26555328 TI - Primitive Spindle Cell Neoplasm of Ileum with Extensive Heterotopic Cartilage, Presenting as Acute Abdomen in a 6-Day-Old Neonate. AB - Neonatal intestinal masses with spindle cell morphology have broad differential diagnoses and require a multidisciplinary approach to make the final diagnosis. Spindle cell masses with heterotopic cartilage in the gastrointestinal tract are very rare, and, to our knowledge, have not previously been reported in the neonate. Here we present a case of intestinal primitive spindle cell neoplasm with extensive heterotopic cartilage that manifested initially as acute abdomen in a 6-day-old term infant. Plain radiography demonstrated pneumoperitoneum, prompting diagnostic laparotomy that identified a perforated mass involving the midileum. Histologic and immunohistochemical examination demonstrated an infiltrative spindle cell tumor most compatible with infantile fibrosarcoma (IFS) by a process of exclusion, with nodules of mature heterotopic cartilage. Additional staging studies did not reveal any evidence of residual or metastatic disease. Recognition of this rare variant of IFS will aid in differentiation from other neonatal intestinal mesenchymal tumors. PMID- 26555329 TI - Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial. AB - BACKGROUND: Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. METHODS AND RESULTS: In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3+/-24.5 versus 69.7+/-24.0, P=0.01) to month 1 (86.6+/-18.1 versus 85.8+/ 18.5, P=0.27) and month 12 (88.4+/-17.8 versus 88.5+/-17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency <=60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. CONCLUSIONS: Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038. PMID- 26555330 TI - Comparing individual and group intervention for psychological adjustment in people with multiple sclerosis: a feasibility randomised controlled trial. AB - OBJECTIVE: To modify a published group intervention for adjustment to multiple sclerosis (MS) to suit an individual format, and to assess the feasibility of a randomised controlled trial (RCT) to compare individual and group intervention for people with multiple sclerosis and low mood. DESIGN: Feasibility randomised controlled trial. SETTING: Participants were recruited through healthcare professionals at a hospital-based multiple sclerosis service and the MS Society. SUBJECTS: People with multiple sclerosis. INTERVENTIONS: Adjustment to multiple sclerosis in individual or group delivery format. MAIN MEASURES: Participants completed mood and quality of life assessments at baseline and at four-month follow-up. Measures of feasibility included: recruitment rate, acceptability of randomisation and the intervention (content and format), and whether the intervention could be adapted for individual delivery. Participants were screened for inclusion using the General Health Questionnaire-12 and Hospital Anxiety and Depression Scale, and were randomly allocated to receive either individual or group intervention, with the same content. RESULTS: Twenty-one participants were recruited (mean age 48.5 years, SD 10.5) and were randomly allocated to individual (n=11) or group (n=10) intervention. Of those offered individual treatment, nine (82%) completed all six sessions. Of those allocated to group intervention, two (20%) attended all six sessions and three (30%) attended five sessions. There were no statistically significant differences between the groups on the outcome measures of mood and quality of life. CONCLUSIONS: The intervention could be provided on an individual basis and the trial design was feasible. There were lower attendance rates at group sessions compared to individual sessions. PMID- 26555331 TI - Correction: Projecting the Hydrologic Impacts of Climate Change on Montane Wetlands. PMID- 26555332 TI - Association between catechol-O-methyltransferase (COMT) Val/Met genotype and smoking cessation treatment with nicotine: a meta-analysis. AB - AIM: Catechol-O-methyltransferase (COMT) is one of the major degradative pathways of dopamine and COMT Val/Met polymorphisms are associated with the enzyme activity, which is related to dopamine involvement in the nicotine addiction process. However, the reported results of several genetic studies are not consistent. MATERIALS & METHODS: We reviewed the smoking cessation outcomes among previously reported studies by comparing COMT polymorphism. A total of five studies were assessed in the present meta-analysis and the Met/Met, Val/Met or Val/Val genotype were compared with respect to smoking cessation outcomes. RESULTS: As the results, any significant association between COMT polymorphism and smoking cessation were not observed. In the subgroup analysis for evaluating the association between COMT polymorphism and smoking cessation therapy, three studies were assessed by comparing two groups (Met/Met vs Val/Met plus Val/Val). A significant association between COMT polymorphism and smoking cessation was observed (odds ratio: 1.871 and 95% CI: 1.382-2.534). CONCLUSION: The COMT polymorphisms are associated with the outcomes following smoking cessation treatment with nicotine. PMID- 26555333 TI - Hypertrophic cardiomyopathy in Donohue syndrome. AB - We report the case of a patient with Donohue syndrome who died of heart failure due to obstructive hypertrophic cardiomyopathy. A literature survey revealed that hypertrophic cardiomyopathy was present in 30% of these patients and was often fatal. Therefore, every patient with Donohue syndrome should be screened for hypertrophic cardiomyopathy. PMID- 26555334 TI - Incremental Value of Live/Real Time Three-Dimensional over Two-Dimensional Transesophageal Echocardiography in the Assessment of Atrial Septal Pouch. AB - An atrial septal pouch (ASP) results from partial fusion of the septum primum and the septum secundum, and depending on the site of fusion, the pouch can be left sided (LASP) or right-sided (RASP). LASPs have been described in association with thrombi found in patients admitted with acute strokes, raising awareness of its potential cardioembolic role, especially in those with no other clearly identifiable embolic source. We retrospectively studied 39 patients in whom the presence of an ASP had been identified by three-dimensional transesophageal echocardiography (3DTEE) and who had a two-dimensional transesophageal echocardiogram (2DTEE) performed during the same clinical encounter. The incremental value provided by 3DTEE over 2DTEE included the detection of six ASPs not found by 2DTEE; the detection of two ASPs in the same subject (in four patients) not identified by 2DTEE; larger ASP measurements of length and height in over 80% of the cases; and measurement of the ASP width (elevational axis) for the calculation of the area of the ASP opening, because of its unique capability to view the pouch en face. In addition, the volume of ASP and of the echogenic masses contained in the ASP (four of 39 patients) could be calculated by 3DTEE, which is a superior parameter of size characterization when compared to individual dimensions. One of these patients who presented with ischemic stroke diagnosed by magnetic resonance imaging had a large (>2 cm) mass in a LASP, with echolucencies similar to those seen in thrombi and associated with clot lysis and resolution. This mass completely disappeared on anticoagulant therapy lending credence that it was most likely a thrombus. There was no history of stroke or any other type of embolic event in the other three patients with masses in ASP. In conclusion, this retrospective study highlights the incremental value of 3DTEE over 2DTEE in the comprehensive assessment and characterization of ASPs, which can aid in the clarification of their role in cryptogenic stroke patients. PMID- 26555335 TI - Single Molecule Fluorescence Microscopy on Planar Supported Bilayers. AB - In the course of a single decade single molecule microscopy has changed from being a secluded domain shared merely by physicists with a strong background in optics and laser physics to a discipline that is now enjoying vivid attention by life-scientists of all venues (1). This is because single molecule imaging has the unique potential to reveal protein behavior in situ in living cells and uncover cellular organization with unprecedented resolution below the diffraction limit of visible light (2). Glass-supported planar lipid bilayers (SLBs) are a powerful tool to bring cells otherwise growing in suspension in close enough proximity to the glass slide so that they can be readily imaged in noise-reduced Total Internal Reflection illumination mode (3,4). They are very useful to study the protein dynamics in plasma membrane-associated events as diverse as cell-cell contact formation, endocytosis, exocytosis and immune recognition. Simple procedures are presented how to generate highly mobile protein-functionalized SLBs in a reproducible manner, how to determine protein mobility within and how to measure protein densities with the use of single molecule detection. It is shown how to construct a cost-efficient single molecule microscopy system with TIRF illumination capabilities and how to operate it in the experiment. PMID- 26555336 TI - Orchid Species Richness along Elevational and Environmental Gradients in Yunnan, China. AB - The family Orchidaceae is not only one of the most diverse families of flowering plants, but also one of the most endangered plant taxa. Therefore, understanding how its species richness varies along geographical and environmental gradients is essential for conservation efforts. However, such knowledge is rarely available, especially on a large scale. We used a database extracted from herbarium records to investigate the relationships between orchid species richness and elevation, and to examine how elevational diversity in Yunnan Province, China, might be explained by mid-domain effect (MDE), species-area relationship (SAR), water energy dynamics (WED), Rapoport's Rule, and climatic variables. This particular location was selected because it is one of the primary centers of distribution for orchids. We recorded 691 species that span 127 genera and account for 88.59% of all confirmed orchid species in Yunnan. Species richness, estimated at 200-m intervals along a slope, was closely correlated with elevation, peaking at 1395 to 1723 m. The elevational pattern of orchid richness was considerably shaped by MDE, SAR, WED, and climate. Among those four predictors, climate was the strongest while MDE was the weakest for predicting the elevational pattern of orchid richness. Species richness showed parabolic responses to mean annual temperature (MAT) and mean annual precipitation (MAP), with maximum richness values recorded at 13.7 to 17.7 degrees C for MAT and 1237 to 1414 mm for MAP. Rapoport's Rule also helped to explain the elevational pattern of species richness in Yunnan, but those influences were not entirely uniform across all methods. These results suggested that the elevational pattern of orchid species richness in Yunnan is collectively shaped by several mechanisms related to geometric constraints, size of the land area, and environments. Because of the dominant role of climate in determining orchid richness, our findings may contribute to a better understanding of the potential effects of climate change on orchid diversity, and the development of conservation strategies for orchids. PMID- 26555337 TI - Response to "Critical Assessment of the Evidence for Striped Nanoparticles". AB - Stirling et al., (10.1371/journal.pone.0108482) presented an analysis on some of our publications on the formation of stripe-like domains on mixed-ligand coated gold nanoparticles. The authors shed doubts on some of our results however no valid argument is provided against what we have shown since our first publication: scanning tunneling microscopy (STM) images of striped nanoparticles show stripe-like domains that are independent of imaging parameters and in particular of imaging speed. We have consistently ruled out the presence of artifacts by comparing sets of images acquired at different tip speeds, finding invariance of the stipe-like domains. Stirling and co-workers incorrectly analyzed this key control, using a different microscope and imaging conditions that do not compare to ours. We show here data proving that our approach is rigorous. Furthermore, we never solely relied on image analysis to draw our conclusions; we have always used the chemical nature of the particles to assess the veracity of our images. Stirling et al. do not provide any justification for the spacing of the features that we find on nanoparticles: ~1 nm for mixed ligand particles and ~ 0.5 nm for homoligand particles. Hence our two central arguments remain unmodified: independence from imaging parameters and dependence on ligand shell chemical composition. The paper report observations on our STM images; none is a sufficient condition to prove that our images are artifacts. We thoroughly addressed issues related to STM artifacts throughout our microscopy work. Stirling et al. provide guidelines for what they consider good STM images of nanoparticles, such images are indeed present in our literature. They conclude that the evidences we provided to date are insufficient, this is a departure from one of the authors' previous article which concluded that our images were composed of artifacts. Given that four independent laboratories have reproduced our measurements and that no scientifically rigorous argument is presented to invalidate our STM images, and also given that Stirling et al. do not contest the quality of our recent STM images, we re-affirm that specific binary mixture of ligands spontaneously form features in their ligand shell that we describe as stripe-like domains ~1 nm in width. PMID- 26555338 TI - Chronic Obstructive Pulmonary Disease-Related Non-Small-Cell Lung Cancer Exhibits a Low Prevalence of EGFR and ALK Driver Mutations. AB - Lung cancer and chronic obstructive pulmonary disease (COPD) are two major lung diseases. Epidermal growth factor receptor (EGFR) mutations, v-Ki-ras2 Kirsten rat sarcoma (KRAS) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements represent driver mutations that are frequently assessed on initial evaluation of non-small-cell lung cancer (NSCLC). The present study focused on the expression of driver mutations in NSCLC patients presenting with COPD and further evaluated the association between NSCLC and COPD. Data from 501 consecutive patients with histologically proven recurrent or metastatic NSCLC were analyzed retrospectively. The patients underwent spirometry and genotyping of EGFR, ALK, and KRAS in tissue samples. Patient characteristics and expression of driver mutations were compared between the COPD and non-COPD groups. Among 350 patients with spirometric results, 106 (30.3%) were diagnosed with COPD, 108 (30.9%) had EGFR mutations, 31 (8.9%) had KRAS mutations, and 34 (9.7%) showed ALK rearrangements. COPD was independently associated with lower prevalences of EGFR mutations (95% confidence interval [CI], 0.254-0.931, p = 0.029) and ALK rearrangements (95% CI, 0.065-0.600, p = 0.004). The proportions of EGFR mutations and ALK rearrangements decreased as the severity of airflow obstruction increased (p = 0.001). In never smokers, the prevalence of EGFR mutations was significantly lower in the COPD group than in the non-COPD group (12.7% vs. 49.0%, p = 0.002). COPD-related NSCLC patients exhibited low prevalences of EGFR mutations and ALK rearrangements compared with the non-COPD group. Further studies are required regarding the molecular mechanisms underlying lung cancer associated with COPD. PMID- 26555339 TI - Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment. AB - Alport syndrome is a genetic disease of collagen IV (alpha3, 4, 5) resulting in renal failure. This study was designed to investigate sex-phenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using Col4a3 knock out (Col4a3KO) mice, an established genetic model of autosomal recessive Alport syndrome. No sex differences in the evolution of body mass loss, renal pathology, biomarkers of tubular damage KIM-1 and NGAL, or deterioration of kidney function were observed during the life span of Col4a3KO mice. These findings confirm that, similar to human autosomal recessive Alport syndrome, female and male Col4a3KO mice develop renal failure at the same age and with similar severity. The specific contribution of macrophage infiltration to Alport disease, one of the prominent features of the disease in human and Col4a3KO mice, remains unknown. This study shows that depletion of kidney macrophages in Col4a3KO male mice by administration of clodronate liposomes, prior to clinical onset of disease and throughout the study period, does not protect the mice from renal failure and interstitial fibrosis, nor delay disease progression. These results suggest that therapy targeting macrophage recruitment to kidney is unlikely to be effective as treatment of Alport syndrome. PMID- 26555340 TI - A Metal-Organic Framework/DNA Hybrid System as a Novel Fluorescent Biosensor for Mercury(II) Ion Detection. AB - Mercury(II) ions have emerged as a widespread environmental hazard in recent decades. Despite different kinds of detection methods reported to sense Hg(2+) , it still remains a challenging task to develop new sensing molecules to replenish the fluorescence-based apparatus for Hg(2+) detection. This communication demonstrates a novel fluorescent sensor using UiO-66-NH2 and a T-rich FAM-labeled ssDNA as a hybrid system to detect Hg(2+) sensitively and selectively. To the best of our knowledge, it has rarely been reported that a MOF is utilized as the biosensing platform for Hg(2+) assay. PMID- 26555342 TI - Abstracts from the Joint Meeting of the Federation of European Physiological Societies and the Baltic Physiological Societies in Kaunas, Lithuania, 26-29 August 2015. PMID- 26555343 TI - Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically Constrained Lysine Analogues. AB - The dynamic post-translational modifications of histones play important roles in the regulation of transcription in animals. The demethylation of N(epsilon) methyl lysine residues in the N-terminal tail of histone H3 is catalyzed by demethylases, of which the largest family is the ferrous iron and 2-oxoglutarate dependent demethylases (JmjC KDMs), which catalyze demethylation via initial hydroxylation of the N-methyl groups. We report studies on the conformational requirements of the JmjC KDM substrates using N-methylated lysine analogues prepared by metathesis reactions of suitably protected N-allylglycine. The results support the proposed requirement for a positively charged N(epsilon) amino group in JmjC KDM catalysis. Demethylation of a trans-C-4/C-5 dehydrolysine substrate analogue was observed with representative KDM4 subfamily members KDM4A, KDM4B and KDM4E, and KDM7B, which are predicted, based on crystallographic analyses, to bind the N(epsilon)-methylated lysine residue in different conformations during catalysis. This information may be useful in the design of JmjC KDM selective inhibitors. PMID- 26555344 TI - Palladium-Catalyzed Synthesis of Delta(2)-Isoxazoline from Toluene Derivatives Enabled by the Triple Role of Silver Nitrate. AB - A palladium-catalyzed direct synthesis of Delta(2)-isoxazoline from toluene derivatives has been established. The present reaction proceeds through nondirected Csp(3)-H activation, benzylic nitration, dehydration, and cycloaddition. This protocol also features the unusual triple role of silver nitrate in a one-pot reaction. PMID- 26555341 TI - Working Memory, Reasoning, and Task Switching Training: Transfer Effects, Limitations, and Great Expectations? AB - Although some studies have shown that cognitive training can produce improvements to untrained cognitive domains (far transfer), many others fail to show these effects, especially when it comes to improving fluid intelligence. The current study was designed to overcome several limitations of previous training studies by incorporating training expectancy assessments, an active control group, and "Mind Frontiers," a video game-based mobile program comprised of six adaptive, cognitively demanding training tasks that have been found to lead to increased scores in fluid intelligence (Gf) tests. We hypothesize that such integrated training may lead to broad improvements in cognitive abilities by targeting aspects of working memory, executive function, reasoning, and problem solving. Ninety participants completed 20 hour-and-a-half long training sessions over four to five weeks, 45 of whom played Mind Frontiers and 45 of whom completed visual search and change detection tasks (active control). After training, the Mind Frontiers group improved in working memory n-back tests, a composite measure of perceptual speed, and a composite measure of reaction time in reasoning tests. No training-related improvements were found in reasoning accuracy or other working memory tests, nor in composite measures of episodic memory, selective attention, divided attention, and multi-tasking. Perceived self-improvement in the tested abilities did not differ between groups. A general expectancy difference in problem-solving was observed between groups, but this perceived benefit did not correlate with training-related improvement. In summary, although these findings provide modest evidence regarding the efficacy of an integrated cognitive training program, more research is needed to determine the utility of Mind Frontiers as a cognitive training tool. PMID- 26555345 TI - Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study. AB - AIM: To evaluate the relationship between idiopathic recurrent pregnancy loss (RPL) and oxidative stress (OS) by means of thiol/disulfide homeostasis via a novel technique. METHODS: Thirty-nine pregnant women diagnosed with idiopathic RPL were compared with 50 healthy pregnant women without a history of abortion. Idiopathic RPL was defined as experiencing two or more consecutive miscarriages prior to 20 weeks of gestation with the presence of normal karyotypes of couple and/or abortus materials, negative maternal screening for anticardiolipin, anti beta 2 glycoprotein antibodies and lupus anticoagulant, normal thyroid stimulating hormone, prolactin and hemoglobin A1C levels and normal pelvic sonography and/or hysterosalpingography. A new and fully automated method was used to measure plasma native thiol, total thiol and disulfide levels, based on the reduction of dynamic disulfide bonds to functional thiol groups by sodium borohydrate. RESULTS: Women with idiopathic RPL had significantly lower plasma levels of native thiol (341.89 +/- 50.0 MUmol/L vs. 390.84 +/- 38.5 MUmol/L, P < 0.001) and total thiol (386.18 +/- 51.7 MUmol/L vs. 435.78 +/- 42.3 MUmol/L, P < 0.001). Disulfide/thiol and disulfide/total thiol ratios were significantly higher in the study group. The native thiol/total thiol ratio was significantly lower in patients with idiopathic RPL. No difference was measured in disulfide, albumin and total protein plasma levels. CONCLUSIONS: The main outcome of our study indicates a relation between idiopathic RPL and OS. More importantly, the new method used in our study proposes a promising, practical and daily applicable test for evaluating patients with idiopathic RPL. PMID- 26555347 TI - Internet-delivered cognitive-behaviour therapy for recent cancer survivors: a feasibility trial. PMID- 26555346 TI - Beyond Measurement and Reward: Methods of Motivating Quality Improvement and Accountability. AB - OBJECTIVE: The article examines public policies designed to improve quality and accountability that do not rely on financial incentives and public reporting of provider performance. PRINCIPAL FINDINGS: Payment policy should help temper the current "more is better" attitude of physicians and provider organizations. Incentive neutrality would better support health professionals' intrinsic motivation to act in their patients' best interests to improve overall quality than would pay-for-performance plans targeted to specific areas of clinical care. Public policy can support clinicians' intrinsic motivation through approaches that support systematic feedback to clinicians and provide concrete opportunities to collaborate to improve care. Some programs administered by the Centers for Medicare & Medicaid Services, including Partnership for Patients and Conditions of Participation, deserve more attention; they represent available, but largely ignored, approaches to support providers to improve quality and protect beneficiaries against substandard care. CONCLUSIONS: Public policies related to quality improvement should focus more on methods of enhancing professional intrinsic motivation, while recognizing the potential role of organizations to actively promote and facilitate that motivation. Actually achieving improvement, however, will require a reexamination of the role played by financial incentives embedded in payments and the unrealistic expectations placed on marginal incentives in pay-for-performance schemes. PMID- 26555348 TI - Safety and immunogenicity of high-dose trivalent inactivated influenza vaccine in adults 50-64 years of age. AB - BACKGROUND: Individuals 50-64 years of age have reduced immune responses to influenza vaccines. The current study examined whether a high-dose inactivated trivalent influenza vaccine (IIV3-HD) might improve immune responses over a standard-dose inactivated influenza vaccine (IIV3-SD) in this age group. METHODS: This was a multicenter, observer-blinded, randomized, active-controlled phase II trial. Adults 50-64 years of age were randomized 1:1 to receive IIV3-HD or IIV3 SD. Hemagglutination inhibition titers were measured before and 28 days after vaccination. Reactogenicity was recorded for 7 days after vaccination and adverse events for 28 days. RESULTS: 148 participants received IIV3-HD and 152 received IIV3-SD. For all vaccine strains, day 28 geometric mean hemagglutination inhibition titers were significantly higher in the IIV3-HD group than in the IIV3 SD group (geometric mean titer ratio [95% confidence interval (CI)]=1.43 [1.04 1.97] for A/H1N1, 1.65 [1.21-2.25] for A/H3N2, and 1.60 [1.23-2.08] for B). Seroconversion rates were significantly higher in the IIV3-HD group than in the IIV3-SD group for strains A/H3N2 and B but not A/H1N1 (difference [95% CI]=13.5% [4.76-22.0] for A/H3N2, 23.1% [11.7-33.6] for B, and -0.2% [-9.66 to 9.18] for A/H1N1). The post-vaccination seroprotection rate was significantly higher in the IIV3-HD group than in the IIV3-SD group for strain B but not for strains A/H1N1 or A/H3N2 (difference=9.1% [2.95-15.7] for B, 2.0% [-0.907 to 5.68] for A/H1N1, and 0.6% [-3.14 to 4.43] for A/H3N2). Reactogenicity was higher in the IIV3-HD group than in the IIV3-SD group, but reactions were mostly of low intensity, transient, and self-limited. Rates of unsolicited adverse events were similar between groups. No serious AEs, AEs leading to early withdrawal, or deaths were reported. CONCLUSIONS: The study suggests that in adults 50-64 years of age, IIV3 HD may improve immunogenicity compared to IIV3-SD while maintaining an acceptable safety profile. PMID- 26555349 TI - Getting the most from the Ebola vaccine success. PMID- 26555350 TI - Public opinion on childhood immunisations in Iceland. AB - INTRODUCTION: In recent years, vaccine preventable diseases such as measles and pertussis have been re-emerging in Western countries, maybe because of decreasing participation in childhood vaccination programs in some countries. There is clear evidence for vaccine efficacy and the risk of adverse effects is low. This needs to be communicated to the general public. The aim of the study was to evaluate the public opinion on childhood vaccinations in Iceland. MATERIALS AND METHODS: An internet based study was used to evaluate the opinion on childhood immunisations in Iceland. The cohort was divided in three groups: (a) general public (b) employees of the University Hospital Iceland and (c) employees (teachers and staff) of the University of Iceland. The cohorts could be stratified according to age, gender, education, household income, parenthood and residency. RESULTS: Responses were received from 5584 individuals (53% response rate). When asked about childhood vaccinations in the first and second year of life, approximately 95% of participants were "positive" or "very positive", approximately 1% were "negative" or "very negative". When participants were asked whether they would have their child immunized according to the Icelandic childhood vaccination schedule, 96% were "positive" or "very positive", 1.2% were "negative" or "very negative". Similarly, 92% trust Icelandic Health authorities to decide on childhood vaccination schedule, 2.3% did not. In total, 9.3% "rather" or "strongly" agreed to the statement "I fear that vaccinations can cause severe adverse effects", 17.5% were undecided and 66.9% "disagreed" or "strongly disagreed". Individuals with higher education were more likely to disagree with this statement (OR=1.45, CI95=1.29-1.64, p<0.001) as did males (OR=1.22, CI95=1.087-1.379, p=0.001). CONCLUSION: This study shows a very positive attitude towards vaccinations raising expectations for an ongoing success in preventing preventable communicable diseases in childhood in Iceland. PMID- 26555351 TI - A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens. AB - Sub-unit vaccines are primarily designed to include antigens required to elicit protective immune responses and to be safer than whole-inactivated or live attenuated vaccines. But their purity and inability to self-adjuvant often result in weaker immunogenicity. Emerging evidence suggests that bio-engineered nanoparticles can be used as immunomodulatory adjuvants. Therefore, in this study we explored the potential of novel Merck-proprietary lipid nanoparticle (LNP) formulations to enhance immune responses to sub-unit viral antigens. Immunization of BALB/c and C57BL/6 mice revealed that LNPs alone or in combination with a synthetic TLR9 agonist, immune-modulatory oligonucleotides, IMO-2125 (IMO), significantly enhanced immune responses to hepatitis B virus surface antigen (HBsAg) and ovalbumin (OVA). LNPs enhanced total B-cell responses to both antigens tested, to levels comparable to known vaccine adjuvants including aluminum based adjuvant, IMO alone and a TLR4 agonist, 3-O-deactytaled monophosphoryl lipid A (MPL). Investigation of the quality of B-cell responses demonstrated that the combination of LNP with IMO agonist elicited a stronger Th1 type response (based on the IgG2a:IgG1 ratio) than levels achieved with IMO alone. Furthermore, the LNP adjuvant significantly enhanced antigen specific cell mediated immune responses. In ELISPOT assays, depletion of specific subsets of T cells revealed that the LNPs elicited potent antigen-specific CD4(+) and CD8(+)T cell responses. Intracellular FACS analyses revealed that LNP and LNP+IMO formulated antigens led to higher frequency of antigen-specific IFNgamma(+)TNFalpha(+)IL-2(+), multi-functional CD8(+)T cell responses, than unadjuvanted vaccine or vaccine with IMO only. Overall, our results demonstrate that lipid nanoparticles can serve as future sub-unit vaccine adjuvants to boost both B-cell and T-cell responses in vivo, and that addition of IMO can be used to manipulate the quality of immune responses. PMID- 26555352 TI - Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients. AB - BACKGROUND: The analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients. METHODS: We performed a subanalysis of a clinical trial that compared the safety and efficacy of high dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-gamma, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-alpha) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [>=4-fold increase in hemagglutination inhibition antibody titers] to >=1 influenza vaccine antigen). RESULTS: Mean baseline IL-6 levels were higher (1.20 versus 0.65pg/mL; P-value=0.021) and IL-2 levels were lower (0.01 versus 0.50pg/mL; P-value=0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02-1.10; P-value=0.002). Vaccination induced an increase in TNF-alpha (P-value <0.0001) and a decrease in IL-5 levels (P value=0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-alpha levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72pg/mL; P-value=0.009). CONCLUSIONS: Baseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4(+) T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients. PMID- 26555353 TI - HIV testing uptake and retention in care of HIV-infected pregnant and breastfeeding women initiated on 'Option B+' in rural Zimbabwe. AB - OBJECTIVES: Zimbabwe has started to scale up Option B+ for the prevention of mother-to-child transmission of HIV, but there is little published information about uptake or retention in care. This study determined the number and proportion of pregnant and lactating women in rural districts diagnosed with HIV infection and started on Option B+ along with six-month antiretroviral treatment (ART) outcomes. METHODS: This was a retrospective record review of women presenting to antenatal care or maternal and child health services at 34 health facilities in Chikomba and Gutu rural districts, Zimbabwe, between January and March 2014. RESULTS: A total of 2728 women presented to care of whom 2598 were eligible for HIV testing: 76% presented to antenatal care, 20% during labour and delivery and 4% while breastfeeding. Of 2097 (81%) HIV-tested women, 7% were HIV positive. Lower HIV testing uptake was found with increasing parity, late presentation to antenatal care, health centre attendance and in women tested during labour. Ninety-one per cent of the HIV-positive women were started on Option B+. Six-month ART retention in care, including transfers, was 83%. Loss to follow-up was the main cause of attrition. Increasing age and gravida status >=2 were associated with higher six-month attrition. CONCLUSION: The uptake of HIV testing and Option B+ is high in women attending antenatal and post-natal clinics in rural Zimbabwe, suggesting that the strategy is feasible for national scale-up in the country. PMID- 26555355 TI - The Challenges of Precision Oncology Drug Development and Implementation. AB - The drivers of precision medicine are clear: for patients (and physicians)--more options, durable clinical benefit, reduced exposure to non-effective drugs and potential to leverage current scientific and technological advances; for the pharmaceutical industry--the potential to tackle core challenges in discovering and developing better and more efficacious medicines, to reduce rates of attrition in drug development and to reduce development costs; for healthcare systems and payers--improved efficiency through the provision of effective care and avoiding ineffective treatments. Oncology has been at the vanguard, the improvements gained in patient survival notable. However, the increasing number of molecular subgroups requires an equally increasing number (and new generation) of highly selective agents targeting inevitably lower incidence molecular segments. Innovative trial designs (umbrella/basket studies) are emerging as a patient-centric approach to drug development, and the rise in public-private partnerships, cross-industry, government and non-profit sector collaborations is enabling implementation of complex clinical trial designs. This poses significant challenges for healthcare systems and regulatory approval. Further substantial evolution of policy and processes, particularly regulatory requirements for approval for new therapeutics, are required. PMID- 26555354 TI - Hippocampus Contributions to Food Intake Control: Mnemonic, Neuroanatomical, and Endocrine Mechanisms. AB - Food intake is a complex behavior that can occur or cease to occur for a multitude of reasons. Decisions about where, when, what, and how much to eat are not merely reflexive responses to food-relevant stimuli or to changes in energy status. Rather, feeding behavior is modulated by various contextual factors and by previous experiences. The data reviewed here support the perspective that neurons in multiple hippocampal subregions constitute an important neural substrate linking the external context, the internal context, and mnemonic and cognitive information to control both appetitive and ingestive behavior. Feeding behavior is heavily influenced by hippocampal-dependent mnemonic functions, including episodic meal-related memories and conditional learned associations between food-related stimuli and postingestive consequences. These mnemonic processes are undoubtedly influenced by both external and internal factors relating to food availability, location, and physiological energy status. The afferent and efferent neuroanatomical connectivity of the subregions of the hippocampus is reviewed with regard to the integration of visuospatial and olfactory sensory information (the external context) with endocrine and gastrointestinal interoceptive stimuli (the internal context). Also discussed are recent findings demonstrating that peripherally derived endocrine signals act on receptors in hippocampal neurons to reduce (leptin, glucagon-like peptide-1) or increase (ghrelin) food intake and learned food reward-driven responding, thereby highlighting endocrine and neuropeptidergic signaling in hippocampal neurons as a novel substrate of importance in the higher-order regulation of feeding behavior. PMID- 26555356 TI - Foot Length, Chest Circumference, and Mid Upper Arm Circumference Are Good Predictors of Low Birth Weight and Prematurity in Ethnic Minority Newborns in Vietnam: A Hospital-Based Observational Study. AB - BACKGROUND: The evaluation of tools to accurately identify low birth weight (LBW) and/or premature newborns in resource-limited countries is a research priority. We explored the use of foot length, chest circumference, and mid-upper arm circumference (MUAC) measured within 24 h as diagnostic tools for identifying newborns who are LBW, premature, or both; and compared measurements taken at birth with those taken at five days of age. MATERIALS AND METHODS: An observational study was undertaken in Hoa Binh Province General Hospital, Vietnam, in ethnic minority newborns. Birth weight, foot length, chest circumference, and MUAC were measured within 24 h of birth and in a subset of 200, were repeated on day five of life. Gestational age was estimated using the New Ballard Score. Receiver Operating Characteristic curves and optimal cut points (the point with the highest sensitivity and specificity where the sensitivity was at least 0.8) were calculated, for predicting prematurity, LBW, and both. Measurements within 24 h and at five days of life were compared. RESULTS: 485 newborns were recruited. Chest circumference and MUAC measured within 24 h of birth were found to be highly predictive of LBW (both yielding area under the curve [AUC] of 0.98, 95% confidence interval [CI] 0.96-0.99), and performed marginally better than foot length (AUC 0.94, 95%CI 0.92-0.96). The optimal cut-points for measurements within 24 h of birth were <= 7.4 cm for foot length; <= 30.4 cm for chest circumference; and <= 9.0 cm for MUAC. There was statistical evidence that anthropometric measurements taken within 24 h of birth were higher than measurements on day five (p<0.02 for all anthropometric measurements) but the magnitude of these differences was small (at most 2mm). CONCLUSIONS: All measurements taken within 24 h of birth were good predictors of LBW, prematurity and both. Differences in measurements taken within 24 h and on day five were not clinically relevant. Further research will ensure that the application of these measures is reliable in community settings. PMID- 26555357 TI - Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam bridge cyclic peptides. AB - Side-chain to side-chain lactam-bridged cyclic peptides have been utilized as therapeutic agents and biochemical tools. Previous synthetic methods of these peptides need special reaction conditions, form side products and take longer reaction times. Herein, an efficient microwave-assisted synthesis of side-chain to side-chain lactam-bridge cyclic peptides SHU9119 and MTII is reported. The synthesis time and efforts are significantly reduced in the present method, without side product formation. The analytical and pharmacological data of the synthesized cyclic peptides are in accordance with the commercially obtained compounds. This new method could be used to synthesize other side-chain to side chain lactam-bridge peptides and amenable to automation and extensive SAR compound derivatization. PMID- 26555358 TI - IgM-enriched solution BT086 improves host defense capacity and energy store preservation in a rabbit model of endotoxemia. AB - INTRODUCTION: The therapeutic value of intravenous immunoglobulin (IVIG) as an adjuvant therapy in sepsis remains debatable. We hypothesized that intravenous administration of BT086, a predominantly IgM IVIG solution, would improve host defense in an established rabbit model of endotoxemia and systemic sepsis. METHODS: New Zealand white rabbits were randomized into the following four groups: (1) the negative control group without lipopolysaccharide (LPS, control), (2) the positive control group with LPS infusion (LPS group), (3) the albumin treated LPS group (ALB+LPS group), and (4) the BT086-treated LPS group (BT086 + LPS group). A standardized amount of E. coli was intravenously injected into all of the animals. The vital parameters, the concentration of E. coli in the blood and other organs, the residual granulocyte phagocytosis activity, and the levels of the inflammatory mediators were measured. Histological changes in the lung and liver tissue were examined following autopsy. RESULTS: The elimination of E. coli from the bloodstream was expedited in the BT086-treated group compared with the LPS- and albumin-treated groups. The BT086 + LPS group exhibited higher phagocytic activity of polymorphonuclear neutrophils (PMNs) than the control and ALB+LPS groups. The liver energy stores were higher in the BT086 + LPS group than in the other groups. CONCLUSION: Our data suggest that the IgM-enriched IVIG has the potential to improve host defense in a rabbit model of endotoxemia. Studies using different animal models and dosages are necessary to further explore the potential benefits of IgM-enriched IVIG solutions. PMID- 26555359 TI - Horizontal Transmission of "Candidatus Liberibacter solanacearum" by Bactericera cockerelli (Hemiptera: Triozidae) on Convolvulus and Ipomoea (Solanales: Convolvulaceae). AB - "Candidatus Liberibacter solanacearum" (Proteobacteria) is an important pathogen of solanaceous crops (Solanales: Solanaceae) in North America and New Zealand, and is the putative causal agent of zebra chip disease of potato. This phloem limited pathogen is transmitted to potato and other solanaceous plants by the potato psyllid, Bactericera cockerelli (Hemiptera: Triozidae). While some plants in the Convolvulaceae (Solanales) are also known hosts for B. cockerelli, previous efforts to detect Liberibacter in Convolvulaceae have been unsuccessful. Moreover, studies to determine whether Liberibacter can be acquired from these plants by B. cockerelli are lacking. The goal of this study was to determine whether horizontal transmission of Liberibacter occurs among potato psyllids on two species of Convolvulaceae, sweet potato (Ipomoea batatas) and field bindweed (Convolvulus arvensis), which grows abundantly in potato growing regions of the United States. Results indicated that uninfected psyllids acquired Liberibacter from both I. batatas and C. arvensis if infected psyllids were present on plants concurrently with the uninfected psyllids. Uninfected psyllids did not acquire Liberibacter from plants if the infected psyllids were removed from the plants before the uninfected psyllids were allowed access. In contrast with previous reports, PCR did detect the presence of Liberibacter DNA in some plants. However, visible amplicons were faint and did not correspond with acquisition of the pathogen by uninfected psyllids. None of the plants exhibited disease symptoms. Results indicate that horizontal transmission of Liberibacter among potato psyllids can occur on Convolvulaceae, and that the association between Liberibacter and Convolvulaceae merits additional attention. PMID- 26555360 TI - Consumption and foraging behaviors for common stimulants (nicotine, caffeine). AB - Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use. PMID- 26555361 TI - Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac. AB - Cysteine-rich peptides (CRPs) are natural products with privileged peptidyl structures that represent a potentially rich source of bioactive compounds. Here, the discovery and characterization of a novel plant CRP family, jasmintides from Jasminum sambac of the Oleaceae family, are described. Two 27-amino acid jasmintides (jS1 and jS2) were identified at the gene and protein levels. Disulfide bond mapping of jS1 by mass spectrometry and its confirmation by NMR spectroscopy revealed disulfide bond connectivity of C-1-C-5, C-2-C-4, and C-3-C 6, a cystine motif that has not been reported in plant CRPs. Structural determination showed that jS1 displays a well-defined structure framed by three short antiparallel beta-sheets. Genomic analysis showed that jasmintides share a three-domain precursor arrangement with a C-terminal mature domain preceded by a long pro-domain of 46 residues and an intron cleavage site between the signal sequence and pro-domain. The compact cysteine-rich structure together with an N terminal pyroglutamic acid residue confers jasmintides high resistance to heat and enzymatic degradation, including exopeptidase treatment. Collectively, these results reveal a new plant CRP structure with an unusual cystine connectivity, which could be useful as a scaffold for designing peptide drugs. PMID- 26555362 TI - Total synthesis of ent-(+)-cinanthrenol A. AB - The first total synthesis of ent-(+)-cinanthrenol A of potent estrogenic activity was achieved with 10.9% overall yield in 13 steps from commercially available materials. Our synthesis features a photo-promoted oxidative 6pi-electron electrocyclization/aromatization for construction of the cyclopenta[a]phenanthren 17-one and Furukawa hydroxyl-directed cyclopropanation for the rare spiro[2,4]heptane. The brevity of this synthetic strategy would allow an expedited access to cinanthrenol A and its analogs for further biological evaluation. PMID- 26555364 TI - Non-monotonic temperature response of polymer mediated interactions. AB - In a recent publication, Feng et al. [Feng et al., Nat. Mater., 2015, 14, 61] reported a very interesting re-entrant solidification behaviour of colloidal particles in an aqueous solution containing polyethylene oxide (PEO). In this system, a crystalline colloidal phase, which is present at low temperatures, melts to a homogeneous fluid upon increasing the temperature. Further raising the temperature, however, eventually gives rise to a flocculated colloidal phase. Feng et al. proposed that the low-temperature crystalline phase is caused by polymer depletion while, at higher temperature, an increased attraction between polymers and particles leads to bridging attractions, and colloidal flocculation. The intermediate temperature regime sees the colloidal interactions dominated by charge repulsion, giving rise to a fluid phase. In the model by Feng et al., polymers are treated as hard spheres, which interact with the colloids via a phenomenological, temperature dependent potential. In this work, we develop a more detailed polymer density functional treatment, based on a model for aqueous PEO solutions that was originally developed by Karlstrom [Karlstrom, J. Phys. Chem., 1985, 89, 4962] for bulk solutions. In this model, monomers are assumed to be in either of two classes of states, labelled A and B, where B is more solvophobic than A. On the other hand, the degeneracy of the B states exceed that of A, causing the population of solvophobic monomers to increase with temperature. If the colloidal particles are also solvophobic, then this model displays the same qualitative temperature response as was observed by Feng et al. That is, at low temperatures, A type monomers predominate and one observes depletion interactions, whereas polymer bridging dominates at higher temperatures, due to the attraction between B-type monomers and the colloidal surface. Interestingly, the intermediate temperature regime is characterized by a polymer mediated interaction between colloids which is repulsive. That is, according to our model the homogeneous fluid phase would form even in the absence of repulsive electrostatic interactions. We emphasize that our model does not rely upon any temperature-dependent interactions. Furthermore, all possible polymer configurations are accounted for, subject to a mean-field Boltzmann weight. Finally, we show that interactions between colloids, mediated by neutral non-grafted polymers, generally follow the trend: attraction => repulsion (or vanishing interaction) => attraction as the surface affinity toward monomers proceeds from repulsive to attractive. PMID- 26555363 TI - Biomonitoring Heavy Metal Pollution Using an Aquatic Apex Predator, the American Alligator, and Its Parasites. AB - Monitoring the bioaccumulation of chemical elements within various organismal tissues has become a useful tool to survey current or chronic levels of heavy metal exposure within an environment. In this study, we compared the bioaccumulations of As, Cd, Cu, Fe, Pb, Se, and Zn between the American alligator, Alligator mississippiensis, and its parasites in order to establish their use as bioindicators of heavy metal pollution. Concomitant with these results, we were interested to determine if parasites were more sensitive bioindicators of heavy metals relative to alligators. We found parasites collectively accumulated higher levels of As, Cu, Se, and Zn in comparison to their alligator hosts, whereas Fe, Cd, and Pb concentrations were higher in alligators. Interestingly, Fe levels were significantly greater in intestinal trematodes than their alligator hosts when analyzed independently from other parasitic taxa. Further analyses showed alligator intestinal trematodes concentrated As, Cu, Fe, Se, and Zn at significantly higher levels than intestinal nematodes and parasites from other organs. However, pentastomids also employed the role as a good biomagnifier of As. Interestingly, parasitic abundance decreased as levels of As increased. Stomach and intestinal nematodes were the poorest bioaccumulators of metals, yet stomach nematodes showed their ability to concentrate Pb at orders of magnitude higher in comparison to other parasites. Conclusively, we suggest that parasites, particularly intestinal trematodes, are superior biomagnifiers of As, Cu, Se, and Zn, whereas alligators are likely good biological indicators of Fe, Cd, and Pb levels within the environment. PMID- 26555365 TI - In-situ gamma-ray survey of rare-earth tailings dams--A case study in Baotou and Bayan Obo Districts, China. AB - An in-situ gamma-ray spectrometer survey with a scintillation detector of NaI(Tl) (Phi75 mm * 75 mm) was carried out in the Baotou and Bayan Obo Districts in order to estimate the levels of natural radionuclides near rare-earth (RE) tailings dams. In the RE tailings dam of Baotou, the mean concentrations of (238)U and (232)Th were 3.0 +/- 1.0 mg/kg (range: 1.9-4.6 mg/kg) and 321 +/- 31 mg/kg (range: 294-355 mg/kg), respectively. In the Bayan Obo tailings dam, the mean concentrations of (238)U and (232)Th were 5.7 +/- 0.5 mg/kg (range: 5.3-6.1 mg/kg) and 276 +/- 0.5 mg/kg (range: 275.5-276.3 mg/kg), respectively. The average (232)Th concentrations in the mining areas of the Bayan Obo Mine and the living areas of the Bayan Obo Town were 18.7 +/- 7.5 and 26.2 +/- 9.1 mg/kg, respectively. The (232)Th concentration recorded in the tailings dams was much higher than the global average (7.44 mg/kg). Our investigation shows that the (232)Th concentration in the tailings in the Baotou dam was 34.6 times greater than that in the local soil (in Guyang County); the average concentrations of (232)Th in the soil in the Baotou District and Bayan Obo Districts were about 1.35 and 2.82 times greater, respectively, than that in the soil in Guyang County. Based on our results, the highest estimated effective dose due to gamma irradiation was 1.15 mSv per year, estimated from the data observed in the Baotou tailings dams. The results of this preliminary study indicate the potential importance of radioactivity in RE tailings dams and that remedial measures may be required. PMID- 26555366 TI - Activity ratios of (234)U/(238)U and (226)Ra/(228)Ra for transport mechanisms of elevated uranium in alluvial aquifers of groundwater in south-western (SW) Punjab, India. AB - The concentrations of total dissolved uranium (U), its isotopic composition ((234)U, (235)U, (238)U) and two long lived Ra isotopes ((226)Ra and (228)Ra) in alluvial aquifers of groundwater were determined to investigate the groundwater flow pattern in the south-western (SW) Punjab, India. Particular attention was given to the spatial variability of activity ratios (ARs) of (234)U/(238)U and (226)Ra/(228)Ra to predict the possible sources and supply process of U into the water from the solid phase. The measured groundwater (234)U/(238)U ARs were ~1 or >1 in the shallow zone (depth < 30 m) with high U concentration and <1 in the deeper zone (depth > 30 m) with relatively low U concentration. The simultaneous elevated U concentration and (234)U/(238)U ARs in waters were possibly due to differences in imprints of rock-water interactions under hydrologic conditions. However, (234)U/(238)U ARs < 1 clearly indicate the lack of recharge from surface water to groundwater leading to (234)U deficit in groundwater. This deficit might be also attributed to alpha recoil processes under strong dissolution. Overall, the decreasing pattern of (234)U/(238)U ARs observed from SE to SW or NW ward clearly indicates a groundwater flow paths from SE to SW/NW. Similarly, (226)Ra/(238)U ARs < 1 for all water samples reflect that the precursor (238)U is fairly mobile relative to (226)Ra. This might be due to unusually high amount of (238)U in groundwaters and subsequently the different geochemistry of the two isotopes. On the other hand, (226)Ra/(228)Ra ARs in groundwaters varied widely and observed about 50-300 times higher than (238)U/(232)Th ARs in granitic rocks or soils. Such elevation in ARs might be attributed to different dissolution properties of their parents during water-rock interactions or lattice damage during decay or local enrichments of uranium in the aquifers. PMID- 26555367 TI - Accumulation of Sellafield-derived radiocarbon ((14)C) in Irish Sea and West of Scotland intertidal shells and sediments. AB - The nuclear energy industry produces radioactive waste at various stages of the fuel cycle. In the United Kingdom, spent fuel is reprocessed at the Sellafield facility in Cumbria on the North West coast of England. Waste generated at the site comprises a wide range of radionuclides including radiocarbon ((14)C) which is disposed of in various forms including highly soluble inorganic carbon within the low level liquid radioactive effluent, via pipelines into the Irish Sea. This (14)C is rapidly incorporated into the dissolved inorganic carbon (DIC) reservoir and marine calcifying organisms, e.g. molluscs, readily utilise DIC for shell formation. This study investigated a number of sites located in Irish Sea and West of Scotland intertidal zones. Results indicate (14)C enrichment above ambient background levels in shell material at least as far as Port Appin, 265 km north of Sellafield. Of the commonly found species (blue mussel (Mytilus edulis), common cockle (Cerastoderma edule) and common periwinkle (Littorina littorea)), mussels were found to be the most highly enriched in (14)C due to the surface environment they inhabit and their feeding behaviour. Whole mussel shell activities appear to have been decreasing in response to reduced discharge activities since the early 2000s but in contrast, there is evidence of continuing enrichment of the carbonate sediment component due to in-situ shell erosion, as well as indications of particle transport of fine (14)C-enriched material close to Sellafield. PMID- 26555369 TI - Measurable effects of local alcohol licensing policies on population health in England. AB - BACKGROUND: English alcohol policy is implemented at local government level, leading to variations in how it is put into practice. We evaluated whether differences in the presence or absence of cumulative impact zones and the 'intensity' of licensing enforcement--both aimed at regulating the availability of alcohol and modifying the drinking environment--were associated with harm as measured by alcohol-related hospital admissions. METHODS: Premises licensing data were obtained at lower tier local authority (LTLA) level from the Home Office Alcohol and Late Night Refreshment Licensing data for 2007-2012, and LTLAs were coded as 'passive', low, medium or highly active based on whether they made use of cumulative impact areas and/or whether any licences for new premises were declined. These data were linked to 2009-2015 alcohol-related hospital admission and alcohol-related crime rates obtained from the Local Alcohol Profiles for England. Population size and deprivation data were obtained from the Office of National Statistics. Changes in directly age-standardised rates of people admitted to hospital with alcohol-related conditions were analysed using hierarchical growth modelling. RESULTS: Stronger reductions in alcohol-related admission rates were observed in areas with more intense alcohol licensing policies, indicating an 'exposure-response' association, in the 2007-2015 period. Local areas with the most intensive licensing policies had an additional 5% reduction (p=0.006) in 2015 compared with what would have been expected had these local areas had no active licensing policy in place. CONCLUSIONS: Local licensing policies appear to be associated with a reduction in alcohol-related hospital admissions in areas with more intense licensing policies. PMID- 26555371 TI - Biomechanical conditioning of tissue engineered heart valves: Too much of a good thing? AB - Surgical replacement of dysfunctional valves is the primary option for the treatment of valvular disease and congenital defects. Existing mechanical and bioprosthetic replacement valves are far from ideal, requiring concomitant anticoagulation therapy or having limited durability, thus necessitating further surgical intervention. Heart valve tissue engineering (HVTE) is a promising alternative to existing replacement options, with the potential to synthesize mechanically robust tissue capable of growth, repair, and remodeling. The clinical realization of a bioengineered valve relies on the appropriate combination of cells, biomaterials, and/or bioreactor conditioning. Biomechanical conditioning of valves in vitro promotes differentiation of progenitor cells to tissue-synthesizing myofibroblasts and prepares the construct to withstand the complex hemodynamic environment of the native valve. While this is a crucial step in most HVTE strategies, it also may contribute to fibrosis, the primary limitation of engineered valves, through sustained myofibrogenesis. In this review, we examine the progress of HVTE and the role of mechanical conditioning in the synthesis of mechanically robust tissue, and suggest approaches to achieve myofibroblast quiescence and prevent fibrosis. PMID- 26555372 TI - Epidemiology of Pediatric Prehospital Basic Life Support Care in the United States. AB - Children have unique medical needs compared to adults. Emergency medical services personnel need proper equipment and training to care for children. The purpose of this study is to characterize emergency medical services pediatric basic life support to help better understand the needs of children transported by ambulance. Pediatric basic life support patients were identified in this retrospective descriptive study. Descriptive statistics were used to examine incident location, possible injury, cardiac arrest, resuscitation attempted, chief complaint, primary symptom, provider's primary impression, cause of injury, and procedures performed during pediatric basic life support calls using the largest aggregate of emergency medical services data available, the 2013 National Emergency Medical Services Information System (NEMSIS) Public Release Research Data Set. Pediatric calls represented 7.4% of emergency medical services activations. Most pediatric patients were male (49.8%), White (40.0%), and of non-Hispanic origin (56.5%). Most incidents occurred in the home. Injury, cardiac arrest, and resuscitation attempts were highest in the 15 to 19 year old age group. Global complaints (37.1%) predominated by anatomic location and musculoskeletal complaints (26.9%) by organ system. The most common primary symptom was pain (30.3%) followed by mental/psychiatric (13.4%). Provider's top primary impression was traumatic injury (35.7%). The most common cause of injury was motor vehicle accident (32.3%). The most common procedure performed was patient assessment (27.4%). Median EMS system response time was 7 minutes (IQR: 5-12). Median EMS scene time was 12 minutes (IQR: 8-19). Median transport time was 14 minutes (IQR: 8-24). Median EMS total call time was 51 minutes (IQR: 33-77). The epidemiology of pediatric basic life support can help to guide efforts in both emergency medical services operations and training. PMID- 26555370 TI - Bioengineered heparins and heparan sulfates. AB - Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan sulfate is a widely distributed membrane and extracellular glycosaminoglycan, heparin is found primarily intracellularly in the granules of mast cells. While heparin has historically received most of the scientific attention for its anticoagulant activity, interest has steadily grown in the multi-faceted role heparan sulfate plays in normal and pathophysiology. The chemical synthesis of these glycosaminoglycans is largely precluded by their structural complexity. Today, we depend on livestock animal tissues for the isolation and the annual commercial production of hundred ton quantities of heparin used in the manufacture of anticoagulant drugs and medical device coatings. The variability of animal-sourced heparin and heparan sulfates, their inherent impurities, the limited availability of source tissues, the poor control of these source materials and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans, driven by both therapeutic applications and as probes to study their natural functions. This review focuses on the complex biology of these glycosaminoglycans in human health and disease, and the use of recombinant technology in the chemoenzymatic synthesis and metabolic engineering of heparin and heparan sulfates. PMID- 26555373 TI - Murine Kidney Transplant Technique. AB - The first mouse kidney transplant technique was published in 1973(1) by the Russell laboratory. Although it took some years for other labs to become proficient in and utilize this technique, it is now widely used by many laboratories around the world. A significant refinement to the original technique using the donor aorta to form the arterial anastomosis instead of the renal artery was developed and reported in 1993 by Kalina and Mottram (2) with a further advancement coming from the same laboratory in 1999 (3). While one can become proficient in this model, a search of the literature reveals that many labs still experience a high proportion of graft loss due to arterial thrombosis. We describe here a technique that was devised in our laboratory that vastly reduces the arterial thrombus reported by others (4,5). This is achieved by forming a heel-and-toe cuff of the donor infra-renal aorta that facilitates a larger anastomosis and straighter blood flow into the kidney. PMID- 26555374 TI - Removal of polycyclic synthetic musks and antineoplastic drugs in ozonated wastewater: Quantitation based on the data of differential spectroscopy. AB - This study examined the degradation behavior of polycyclic musks (PMs) and antineoplastic drugs (ADs) and the absorbance spectra of effluent organic matter (EfOM) in municipal wastewater by ozone. Specific ozone doses used in the experiments ranged from 0 to 1mg O3/mg dissolved organic matter (DOC). The examined PMs included galaxolide, tonalide, celestolide, traseolide and phantolide. ADs included busulfan, chlorambucil, cyclophosphamide, dacarbazine, flutamide, ifosfamide, tamoxifen and methotrexate. Strong monotonic albeit nonlinear correlations were found to exist between relative changes of EfOM absorbance at 254 nm (i.e. DeltaA254/A(0)254) and the degradation of the selected PMs and ADs. This result was interpreted based on the concept of the simultaneous oxidation of EfOM and, on the other hand, PMs and ADs. This interpretation showed that PMs were degraded primarily via OH radical attack, with tonalide and phantolide being less reactive compared with the other PMs. ADs such as cyclophosphamide, ifosfamide and busulfan were also determined to undergo oxidation by OH radicals. Comparison of the behavior of the radical probe para chlorobenzoic acid and the examined ADs and PMs allowed evaluating corresponding reaction rate constants for reactions between these species and OH radicals. PMID- 26555375 TI - FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma. AB - BACKGROUND AND AIMS: Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to multi-kinase inhibitors targeting FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted. METHODS: This study was designed to investigate the prevalence and clinical significance of FGFR1 amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence in situ hybridization (FISH) analysis. RESULTS: FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 copy numbers >= 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between FGFR1 amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of FGFR1 amplification, all available tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of FGFR1 amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with FGFR1 amplified primary cancers. CONCLUSIONS: In conclusion, FGFR1 amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt for clinical studies in this tumor type. PMID- 26555376 TI - Impaired primary mouse myotube formation on crosslinked type I collagen films is enhanced by laminin and entactin. AB - In skeletal muscle, the stem cell niche is important for controlling the quiescent, proliferation and differentiation states of satellite cells, which are key for skeletal muscle regeneration after wounding. It has been shown that type I collagen, often used as 3D-scaffolds for regenerative medicine purposes, impairs myoblast differentiation. This is most likely due to the absence of specific extracellular matrix proteins providing attachment sites for myoblasts and/or myotubes. In this study we investigated the differentiation capacity of primary murine myoblasts on type I collagen films either untreated or modified with elastin, laminin, type IV collagen, laminin/entactin complex, combinations thereof, and Matrigel as a positive control. Additionally, increased reactive oxygen species (ROS) and ROCK signaling might also be involved. To measure ROS levels with live-cell microscopy, fibronectin-coated glass coverslips were additionally coated with type I collagen and Matrigel onto which myoblasts were differentiated. On type I collagen-coated coverslips, myotube formation was impaired while ROS levels were increased. However, anti-oxidant treatment did not enhance myotube formation. ROCK inhibition, which generally improve cellular attachment to uncoated surfaces or type I collagen, enhanced myoblast attachment to type I collagen-coated coverslips and -films, but slightly enhanced myotube formation. Only modification of type I collagen films by Matrigel and a combination of laminin/entactin significantly improved myotube formation. Our results indicate that type I collagen scaffolds can be modified by satellite cell niche factors of which specifically laminin and entactin enhanced myotube formation. This offers a promising approach for regenerative medicine purposes to heal skeletal muscle wounds. STATEMENT OF SIGNIFICANCE: In this manuscript we show for the first time that impaired myotube formation on type I collagen scaffolds can be completely restored by modification with laminin and entactin, two extracellular proteins from the satellite cell niche. This offers a promising approach for regenerative medicine approaches to heal skeletal muscle wounds. PMID- 26555378 TI - Polysaccharide-based antibiofilm surfaces. AB - Surface treatment by natural or modified polysaccharide polymers is a promising means to fight against implant-associated biofilm infections. The present review focuses on polysaccharide-based coatings that have been proposed over the last ten years to impede biofilm formation on material surfaces exposed to bacterial contamination. Anti-adhesive and bactericidal coatings are considered. Besides classical hydrophilic coatings based on hyaluronic acid and heparin, the promising anti-adhesive properties of the algal polysaccharide ulvan are underlined. Surface functionalization by antimicrobial chitosan and derivatives is extensively surveyed, in particular chitosan association with other polysaccharides in layer-by-layer assemblies to form both anti-adhesive and bactericidal coatings. STATEMENT OF SIGNIFICANCE: Bacterial contamination of surfaces, leading to biofilm formation, is a major problem in fields as diverse as medicine, first, but also food and cosmetics. Many prophylactic strategies have emerged to try to eliminate or reduce bacterial adhesion and biofilm formation on surfaces of materials exposed to bacterial contamination, in particular implant materials. Polysaccharides are widely distributed in nature. A number of these natural polymers display antibiofilm properties. Hence, surface treatment by natural or modified polysaccharides is a promising means to fight against implant-associated biofilm infections. The present manuscript is an in depth look at polysaccharide-based antibiofilm surfaces that have been proposed over the last ten years. This review, which is a novelty compared to published literature, will bring well documented and updated information to readers of Acta Biomaterialia. PMID- 26555379 TI - Complications of intravitreal ocriplasmin for vitreomacular traction and macular hole: a prospective spectral-domain optical coherence tomography study. AB - OBJECTIVE: The purpose of this study was to evaluate the safety of intravitreal ocriplasmin prospectively, reporting potential complications in patients with vitreomacular traction (VMT) alone or associated with macular hole (MH). MATERIALS AND METHODS: Participants in this prospective, multicenter study, were 24 patients with VMT (17 with VMT alone and seven with MH combined with VMT). All patients were treated with a single ocriplasmin injection and followed-up prospectively at baseline, day 7, 28 and the last examination of the follow-up for each patient (mean +/- SD: 64.2 +/- 24.4 d, range: 40-145 d). Best-corrected visual acuity (BCVA) was assessed, and spectral-domain optical coherence tomography was performed at each visit while the percentage of resolution of VMT and the association with various potential adverse events were recorded and analyzed. RESULTS: 66.7% of patients presented VMT release at the end of the follow-up, while 28.6% exhibited MH closure. Severe adverse events, such as enlargement of preexisting MH and formation of lamellar MH, were observed in one and four cases, respectively and remained till the end of the follow-up. Moderate adverse events, such as ellipsoid zone disruption and subretinal fluid development, became evident seven days after injection, in four cases. Formation of cystoid macular edema (CME), not evident at baseline, was noticed in three cases at day 28 after injection. Mild adverse events, like vitreous floaters, photopsias, eye pain and foreign body sensation, were noticed at day 7 and resolved till the end of the follow-up. CONCLUSIONS: Mild and moderate adverse events occurred mainly during the first week of the follow-up, while severe adverse events, such as the lamellar MH formation and CME at day 28 post injection were seen. PMID- 26555377 TI - Engineering growth factors for regenerative medicine applications. AB - Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications. STATEMENT OF SIGNIFICANCE: Growth factors are promising therapeutic proteins that have the ability to modulate morphogenetic behaviors, including cell survival, proliferation, migration and differentiation. However, the translation of growth factors into clinical therapies has been hindered by properties such as poor protein stability, low recombinant expression yield, and non-physiological delivery, which lead to suboptimal efficacy and adverse side effects. To address these needs, researchers are employing clever molecular and material engineering and design strategies to both improve the intrinsic properties of growth factors and effectively control their delivery into tissue. This review highlights examples of interdisciplinary tools and technologies used to augment the therapeutic potential of growth factors for clinical applications in regenerative medicine. PMID- 26555380 TI - Coping with pregnancy after 9months in the dark: Post-hibernation buffering of high maternal stress in arctic ground squirrels. AB - Pregnancy and lactation are key times in the life of female mammals when energetic resources must be brought to bear to produce and nurture offspring. Changes in glucocorticoid (GC) levels are central to this objective, due to their roles in modulating development and physiology and in mediating energetic tradeoffs. We examined GC changes over reproduction in a species living in a harsh seasonal environment: the arctic ground squirrel (Urocitellus parryii). Females become pregnant immediately after emerging from a ~9month hibernation, and then must begin this pregnancy during an additional month of freezing temperatures and limited food availability. We measured plasma levels of total cortisol, corticosteroid-binding globulin (CBG), and free cortisol in unstressed females at three stages: not-visibly pregnant, visibly pregnant, and lactating. Total cortisol levels were similar in all stages, but CBG levels increased 4-fold from the not-visibly pregnant stage to visibly pregnant and lactating stage. As a result, the free cortisol fraction declined from 51% of total cortisol when females were not-visibly pregnant to only 5% when they were visibly pregnant (remaining low and stable throughout pregnancy) and 10% when they were lactating. This pattern is markedly different from that seen in other mammals, where 10% or less of GCs are free and these tend to increase during gestation. We postulate that the high free cortisol just prior to visible pregnancy is a seasonal adaptation relating either to the pronounced physiological changes the female must undergo after emerging from hibernation and immediately getting pregnant, or to the mobilization of body reserves for energy to permit pregnancy, or both. Thereafter, high CBG levels may shield the developing offspring from the negative effects of cortisol overexposure. PMID- 26555381 TI - Active droplet generation in microfluidics. AB - The reliable generation of micron-sized droplets is an important process for various applications in droplet-based microfluidics. The generated droplets work as a self-contained reaction platform in droplet-based lab-on-a-chip systems. With the maturity of this platform technology, sophisticated and delicate control of the droplet generation process is needed to address increasingly complex applications. This review presents the state of the art of active droplet generation concepts, which are categorized according to the nature of the induced energy. At the liquid/liquid interface, an energy imbalance leads to instability and droplet breakup. PMID- 26555382 TI - Immunomodulatory effects of epicatechin-(2beta->O->7, 4beta->8)-ent-epicatechin isolated from Rhododendron spiciferum in vitro. AB - CONTEXT: Many traditional Chinese medicines (TCMs) can act as either immunosuppresants or immunostimulants, properties that have lead to their increasing use as immunomodulators in the treatment of disease. Recently, our lab successfully identified a dimer epicatechin-(2beta->O -> 7, 4beta->8)-ent epicatechin (EEE) from the chloroform extract of Rhododendron spiciferum. OBJECTIVE: To evaluate the immunomodulatory effects of EEE in vitro. MATERIALS AND METHODS: Splenocytes, peritoneal macrophages and peripheral blood mononuclear cells from BALB/c mice were incubated with different concentrations of EEE. RESULTS: EEE significantly stimulates splenocyte proliferation when administered either alone or in combination with concanavalin A (Con A), lipopolysaccharide (LPS), and Anti-CD3. EEE enhances the cytotoxicity of natural killer (NK) cells markedly and phagocytic function of macrophage. Moreover, we found that the levels of several helper T1 (Th1) cytokines, including interleukin-2 (IL-2), IL 12, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are significantly increased after EEE treatment, while the levels of Th2 cytokine IL 4 and IL-10 are significantly decreased. As a result, the ratio of Th1/Th2 is significantly increased in the presence of EEE. EEE also increased CD4 and CD8 cell populations. CONCLUSION: These results indicate that EEE exhibits immunomodulatory activity and suggests that this compound could be developed as a novel immunotherapeutic agent for treating cancer and other immune-mediated diseases. PMID- 26555383 TI - Spectroscopic studies of interaction between CuO nanoparticles and bovine serum albumin. AB - Recently, the great interests in manufacturing and application of metal oxide nanoparticles in commercial and industrial products have led to focus on the potential impact of these particles on biomacromolecules. In the present study, the interaction of copper oxide (CuO) nanoparticles with bovine serum albumin (BSA) was studied by spectroscopic techniques. The zeta potential value for BSA and CuO nanoparticles with average diameter of around 50 nm at concentration of 10 MUM in the deionized (DI) water were -5.8 and -22.5 mV, respectively. Circular dichroism studies did not show any changes in the content of secondary structure of the protein after CuO nanoparticles interaction. Fluorescence data revealed that the fluorescence quenching of BSA by CuO nanoparticles was the result of the formed complex of CuO nanoparticles - BSA. Binding constants and other thermodynamic parameters were determined at three different temperatures. The hydrogen bond interactions are the predominant intermolecular forces to stabilize the CuO nanoparticle - BSA complex. This study provides important insight into the interaction of CuO nanoparticles with proteins, which may be of importance for further application of these nanoparticles in biomedical applications. PMID- 26555384 TI - Children with developmental coordination disorder demonstrate a spatial mismatch when estimating coincident-timing ability with tools. AB - Coincident timing or interception ability can be defined as the capacity to precisely time sensory input and motor output. This study compared accuracy of typically developing (TD) children and those with Developmental Coordination Disorder (DCD) on a task involving estimation of coincident timing with their arm and various tool lengths. Forty-eight (48) participants performed two experiments where they imagined intercepting a target moving toward (Experiment 1) and target moving away (Experiment 2) from them in 5 conditions with their arm and tool lengths: arm, 10, 20, 30, and 40 cm. In Experiment 1, the DCD group overestimated interception points approximately twice as much as the TD group, and both groups overestimated consistently regardless of the tool used. Results for Experiment 2 revealed that those with DCD underestimated about three times as much as the TD group, with the exception of when no tool was used. Overall, these results indicate that children with DCD are less accurate with estimation of coincident timing; which might in part explain their difficulties with common motor activities such as catching a ball or striking a baseball pitch. PMID- 26555385 TI - Early communicative behaviors and their relationship to motor skills in extremely preterm infants. AB - Despite the predictive value of early spontaneous communication for identifying risk for later language concerns, very little research has focused on these behaviors in extremely low-gestational-age infants (ELGA<28 weeks) or on their relationship with motor development. In this study, communicative behaviors (gestures, vocal utterances and their coordination) were evaluated during mother infant play interactions in 20 ELGA infants and 20 full-term infants (FT) at 12 months (corrected age for ELGA infants). Relationships between gestures and motor skills, evaluated using the Bayley-III Scales were also examined. ELGA infants, compared with FT infants, showed less advanced communicative, motor, and cognitive skills. Giving and representational gestures were produced at a lower rate by ELGA infants. In addition, pointing gestures and words were produced by a lower percentage of ELGA infants. Significant positive correlations between gestures (pointing and representational gestures) and fine motor skills were found in the ELGA group. We discuss the relevance of examining spontaneous communicative behaviors and motor skills as potential indices of early development that may be useful for clinical assessment and intervention with ELGA infants. PMID- 26555386 TI - Scope of practice of optometrists working in the UK Hospital Eye Service: a national survey. AB - PURPOSE: The role of the optometrist in the Hospital Eye Service (HES) has undergone significant development in recent years to include extended areas of clinical practice more traditionally undertaken by ophthalmologists, commensurate with a growing demand for increased capacity in ophthalmic services. In this report, we present the findings from a national survey of the scope of practice of optometrists working in the UK HES. METHODS: A survey was designed to incorporate questions on the provision of core services before seeking detailed information on the scope of practice within extended roles to include: ophthalmic sub-specialist areas where optometrists currently practice; the undertaking of specific procedures within these services; the relative autonomy of practice within these extended roles; and the training and accreditation requirements for working within extended roles. SurveyMonkey was used to disseminate the survey to the head of optometry in 79 HES units throughout the UK. RESULTS: Responses were received from 70 of the 79 (89%) survey invitations. A substantial majority of respondents (N = 67/70, 96%) indicated that optometrists undertook extended roles. Glaucoma is the leading extended role service provided by optometrists (92% of respondents providing extended role services), with roles in macula (71%), medical retina/diabetes (67%), cataract (55%) and corneal services (55%) also being relatively common. A wide variety of clinical procedures or interventions are undertaken as part of these services, which for a small number of optometrists now also includes the undertaking of specific laser procedures. There is evidence for a significant degree of autonomy within these extended roles. The primary mode of training is an 'apprentice' model, incorporating sessions worked under supervision in ophthalmology clinics. Methods of accreditation for optometric participation in extended role services are varied. CONCLUSIONS: While optometrists working within the UK HES continue to undertake the traditional clinical roles of refraction, clinically necessary contact lenses, and low vision rehabilitation, it is clear that these professionals now undertake a wide range of extended clinical roles, with a transformed scope of practice now incorporating diverse roles traditionally undertaken by medical practitioners. PMID- 26555388 TI - 33rd Annual Meeting of the European Society for Paediatric Infectious Diseases in Leipzig, Germany. PMID- 26555387 TI - Atypical RhoV and RhoU GTPases control development of the neural crest. AB - This review addresses the developmental roles of 2 GTPases of the Rho family, RhoV/Chp and RhoU/Wrch. These two GTPases form a distinct subfamily related to Rac and Cdc42 proteins and were detected in a screen for Rho members that are particularly expressed in the neural crest, an embryonic tissue peculiar to vertebrates. The neural crest represents a physiological model of normal epithelial to mesenchymal transition (EMT), in which epithelial cells at the border of neural and non-neural ectoderm differentiate, lose their intercellular connections and migrate throughout the embryo. We showed that RhoV, transiently induced by the canonical Wnt pathway, is required for the full differentiation of neural crest cells, while RhoU, induced later by the non-canonical Wnt pathway, is necessary for the migration process. These two GTPases, which are highly conserved across vertebrates, are thus tightly functionally linked to Wnt signaling, whose implication in embryonic development and cancer progression is well established. In the light of the recent literature, we discuss how RhoV and RhoU may achieve their physiological functions. PMID- 26555389 TI - Global Vaccine Safety Assessment: Challenges and Opportunities. PMID- 26555390 TI - Massive horizontal gene transfer, strictly vertical inheritance and ancient duplications differentially shape the evolution of Bacillus cereus enterotoxin operons hbl, cytK and nhe. AB - BACKGROUND: Bacillus cereus sensu lato comprises eight closely related species including the human pathogens Bacillus anthracis and Bacillus cereus. Within B. cereus sensu lato, chromosomally and plasmid-encoded toxins exist. While plasmid mediated horizontal gene transfer of the emetic toxin, anthrax and insecticidal toxins is known, evolution of enterotoxin genes within the group has not been studied. RESULTS: We report draft genome assemblies of 25 strains, a phylogenetic network of 142 strains based on ANI derived from genome sequences and a phylogeny based on whole-genome SNP analysis. The data clearly support subdivision of B. cereus sensu lato into seven phylogenetic groups. While group I, V and VII represent B. pseudomycoides, B. toyonensis and B. cytotoxicus, which are distinguishable at species level (ANI border >= 96 %), strains ascribed to the other five species do not match phylogenic groups. The chromosomal enterotoxin operons nheABC and hblCDAB are abundant within B. cereus both isolated from infections and from the environment. While the duplicated hbl variant hbl a is present in 22 % of all strains investigated, duplication of nheABC is extremely rare (0.02 %) and appears to be phylogenetically unstable. Distribution of toxin genes was matched to a master tree based on seven concatenated housekeeping genes, which depicts species relationships in B. cereus sensu lato as accurately as whole-genome comparisons. Comparison to the phylogeny of enterotoxin genes uncovered ample evidence for horizontal transfer of hbl, cytK and plcR, as well as frequent deletion of both toxins and duplication of hbl. No evidence for nhe deletion was found and stable horizontal transfer of nhe is rare. Therefore, evolution of B. cereus enterotoxin operons is shaped unexpectedly different for yet unknown reasons. CONCLUSIONS: Frequent exchange of the pathogenicity factors hbl, cytK and plcR in B. cereus sensu lato appears to be an important mechanism of B. cereus virulence evolution, including so-called probiotic or non-pathogenic species, which might have consequences for risk assessment procedures. In contrast, exclusively vertical inheritance of nhe was observed, and since nhe negative strains appear to be extremely rare, we suggest that fitness loss may be associated with deletion or horizontal transfer of the nhe operon. PMID- 26555391 TI - A Novel Hyperspectral Feature-Extraction Algorithm Based on Waveform Resolution for Raisin Classification. AB - Near-infrared hyperspectral imaging technology was adopted in this study to discriminate among varieties of raisins produced in Xinjiang Uygur Autonomous Region, China. Eight varieties of raisins were used in the research, and the wavelengths of the hyperspectral images were from 900 to 1700 nm. A novel waveform resolution method is proposed to reduce the hyperspectral data and extract the features. The waveform-resolution method compresses the original hyperspectral data for one pixel into five amplitudes, five frequencies, and five phases for 15 feature values in all. A neural network was established with three layers-eight neurons for the first layer, three neurons for the hidden layer, and one neuron for the output layer-based on the 15 features used to determine the varieties of raisins. The accuracies of the model, which are presented as sensitivity, precision, and specificity, for the testing data set, are 93.38, 81.92, and 99.06%. This is higher than the accuracies of the model using a conventional principal component analysis feature-extracting method combined with a neural network, which has a sensitivity of 82.13%, precision of 82.22%, and specificity of 97.45%. The results indicate that the proposed waveform-resolution feature-extracting method combined with hyperspectral imaging technology is an efficient method for determining varieties of raisins. PMID- 26555392 TI - Lights and shadows of cardiac magnetic resonance imaging in acute myocarditis. AB - Cardiac magnetic resonance (CMR) is considered a primary tool for the diagnosis of acute myocarditis, due to its unique potential for non-invasive identification of the various hallmarks of the inflammatory response, with relevant impact on patient management and prognosis. Nonetheless, a marked variation in sensitivity and negative predictive value has been reported in the literature, reflecting the intrinsic drawbacks of current diagnostic criteria, which are based mainly on the use of conventional CMR pulse sequences. As a consequence, a negative exam cannot reliably exclude the diagnosis, especially in patients who do not present an infarct-like onset of disease. The introduction of new-generation mapping techniques further widened CMR potentials, allowing quantification of tissue changes and opening new avenues for non-invasive workup of patients with inflammatory myocardial disease. MAIN MESSAGES: * CMR sensitivity varies in AM, reflecting its clinical polymorphism and the intrinsic drawbacks of LLc. * Semiquantitative approaches such as EGEr or T2 ratio have limited accuracy in diffuse disease forms. * T1 mapping allows objective quantification of inflammation, with no need to normalize measurements. * A revised protocol including T2-STIR, T1 mapping and LGE could be hypothesized to improve sensitivity. PMID- 26555393 TI - Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection. AB - Herpes simplex virus (HSV) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (HPV) is now the accepted causative agent, the epidemiological link between HSV and HPV-associated cancers persists. The annexin A2 heterotetramer (A2t) has been shown to mediate infectious HPV type 16 (HPV16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (SLPI), an endogenous A2t ligand, inhibits HPV16 uptake and infection. Interestingly, HSV infection induces a sustained downregulation of SLPI in epithelial cells, which we hypothesized promotes HPV16 infection through A2t. Here, we show that in vitro infection of human keratinocytes with HSV-1 or HSV-2, but not with an HSV-1 ICP4 deletion mutant that does not downregulate SLPI, leads to a >70% reduction of SLPI mRNA and a >60% decrease in secreted SLPI protein. Consequently, we observed a significant increase in the uptake of HPV16 virus-like particles and gene transduction by HPV16 pseudovirions (two- and 2.5-fold, respectively) in HSV-1- and HSV-2 infected human keratinocyte cell cultures compared with uninfected cells, whereas exogenously added SLPI reversed this effect. Using a SiMPull (single-molecule pulldown) assay, we demonstrated that endogenously secreted SLPI interacts with A2t on epithelial cells in an autocrine/paracrine manner. These results suggested that ongoing HSV infection and resultant downregulation of local levels of SLPI may impart a greater susceptibility for keratinocytes to HPV16 infection through the host cell receptor A2t, providing a mechanism that may, in part, provide an explanation for the aetiological link between HSV and HPV-associated cancers. PMID- 26555395 TI - Elevation of Ca19-9 tumor antigen in colorectal cancer: an in silico investigation of pathogenesis. PMID- 26555394 TI - Associations between venous thromboembolism onset, D-dimer, and soluble fibrin monomer complex after total knee arthroplasty. AB - BACKGROUND: Prevention and early detection of venous thromboembolism (VTE) is important after arthroplasty of the lower limb. The purpose of this study was to investigate the associations between VTE and hemostatic markers after minimally invasive total knee arthroplasty (MIS-TKA). METHODS: We performed a retrospective study of 50 patients (55 knees) who underwent primary unilateral MIS-TKA with periodic determination of D-dimer and soluble fibrin monomer complex (SFMC) concentrations and with ultrasonography. The development of symptomatic and asymptomatic VTE, location of deep venous thrombosis (DVT; proximal or distal), changes in SFMC and D-dimer concentrations, and correlations between hemostatic markers and VTE onset were evaluated. RESULTS: Twenty-six patients (47%) had an asymptomatic distal DVT, but none had proximal DVT, pulmonary embolism, or symptomatic DVT. DVT was detected at postoperative day 1 (POD1) in 16 patients, POD3 in six, and POD5 in three (excluding detections of the same DVT in the same position on different days). DVT onset correlated significantly with SFMC concentration on POD1 and with D-dimer concentration on POD3. The D-dimer concentration did not differ significantly between patients who developed DVT (DVT+) and those who did not (DVT-) at each postoperative time. SFMC concentration differed between DVT+ and DVT- patients only on POD1. Analysis of each hemostatic marker classified as either within or outside the normal concentration range showed no significant correlations between D-dimer concentration and DVT onset at each period. There were significant correlations between SFMC concentrations and DVT onset on POD1 and POD3. There were also significant correlations between D-dimer positive (+) findings and/or SFMC+ findings and DVT onset on POD1 and POD3. D-dimer+ and/or SFMC+ findings had better specificity on POD1 and a positive predictive value on POD1 and POD3 compared with SFMC+ alone. CONCLUSIONS: SFMC concentration is an effective hemostatic marker for early detection of DVT. D-dimer concentration alone has limited value as a hemostatic marker for early detection of DVT. Measurement of both D-dimer and SFMC concentrations might be a more sensitive diagnostic tool than measuring SFMC concentration alone. PMID- 26555396 TI - A novel approach to retrieve a retained wireless video capsule in an unknown location, which has been asymptomatic for 21 months and review of the literature. PMID- 26555397 TI - A new potential secretion pathway for recombinant proteins in Bacillus subtilis. AB - BACKGROUND: Secretion of cytoplasmic expressed proteins into growth media has significant advantages. Due to the lack of an outer membrane, Bacillus subtilis is considered as a desirable 'cell factory' for the secretion of recombinant proteins. However, bottlenecks in the classical pathway for the secretion of recombinant proteins limit its use on a wide scale. In this study, we attempted to use four typical non-classically secreted proteins as signals to export three recombinant model proteins to the culture medium. RESULTS: All four non classically secreted proteins can direct the export of the intrinsically disordered nucleoskeletal-like protein (Nsp). Two of them can guide the secretion of alkaline phosphatase (PhoA). One can lead the secretion of the thermostable beta-galactosidase BgaB, which cannot be secreted with the aid of typical Sec dependent signal peptides. CONCLUSION: Our results show that the non-classically secreted proteins lead the recombinant proteins to the culture medium, and thus non-classical protein secretion pathways can be exploited as a novel secretion pathway for recombinant proteins. PMID- 26555400 TI - Genomics going wild: Marine sampling for studies of evolution and development. PMID- 26555398 TI - Behavioural and biochemical changes in maternally separated Sprague-Dawley rats exposed to restraint stress. AB - Early life adversity has been associated with the development of various neuropsychiatric disorders in adulthood such as depression and anxiety. The aim of this study was to determine if stress during adulthood can exaggerate the depression-/anxiety-like behaviour observed in the widely accepted maternally separated (MS) Sprague-Dawley (SD) rat model of depression. A further aim was to determine whether the behavioural changes were accompanied by changes in hippocampal brain-derived neurotrophic factor (BDNF) and the protein profile of the prefrontal cortex (PFC). Depression-/anxiety-like behaviour was measured in the elevated plus maze, open field and forced swim test (FST) in the MS SD rats exposed to chronic restraint stress in adulthood. As expected, MS increased immobility of SD rats in the FST but restraint stress did not enhance this effect of MS on SD rats. A proteomic analysis of the PFC revealed a decrease in actin related proteins in MS and non-separated rats subjected to restraint stress as well as a decrease in mitochondrial energy-related proteins in the stressed rat groups. Since MS during early development causes a disruption in the hypothalamic pituitary-adrenal axis and long-term changes in the response to subsequent stress, it may have prevented restraint stress from exerting its effects on behaviour. Moreover, the decrease in proteins related to mitochondrial energy metabolism in MS rats with or without subsequent restraint stress may be related to stress per se and not depression-like behaviour, because rats subjected to restraint stress displayed similar decreases in energy-related proteins and spent less time immobile in the FST than control rats. PMID- 26555399 TI - Phage display screening identifies a novel peptide to suppress ovarian cancer cells in vitro and in vivo in mouse models. AB - BACKGROUND: Ovarian cancer is a possibly lethal gynecological malignancy and this study utilized phage display technology to screen and identify peptides that specifically bind to ovarian cancer cells and explored the effects of these peptides on ovarian cancer cells in vitro and in vivo. METHODS: The phage displayed peptide library was used to isolate the peptides binding to and internalizing into the ovarian carcinoma cells. Positive phage clones were characterized with DNA sequencing and bioinformatics analysis and then validated with immunofluorescence. Subsequently, the selected peptides were investigated for their cancer-related functions, including cell adhesion, spreading, motility, and invasion in vitro and in vivo. RESULTS: Peptide1 read as SWQIGGNwas the positive peptide and showed preferential binding to the target cells. Peptide 1 also inhibited cell proliferation, migration, invasion and adhesion of ovarian cancer HO8910 cells in vitro. In vivo, Peptide 1 led to a lower tumorigenicity of HO8910 cells, which was characterized by the inhibitory effect on tumor growth and metastasis of ovarian cells. CONCLUSION: These studies demonstrate that the phage display-identified tumor cell-binding peptide was able to control ovarian cancer cell viability, migration, invasion, and adhesion capacity in vitro as well as tumor growth and metastasis in vivo. Future studies will be aimed at evaluating the clinical efficacy of the peptide SWQIGGN in ovarian cancer patients. PMID- 26555401 TI - The marine genome: structure, regulation and evolution. PMID- 26555402 TI - The phytoremediation of an organic and inorganic polluted soil: A real scale experience. AB - A phytoremediation process with horse manure, plants (Populus alba, Cytisus scoparius, Paulownia tomentosa) and naturally growing vegetation was carried out at a real-scale in order to phytoremediate and functionally recover a soil contaminated by metals (Zn, Pb, Cd, Ni, Cu, Cr), hydrocarbons (TPH) and polychlorobiphenyls (PCB). All the plants were effective in two years in the reclamation of the polluted soil, showing an average reduction of about 35%, 40%, and 70% in metals, TPH and PCB content, respectively. As regards the plants, the poplar contributed the most to organic removal. In fact, its ability to take up and detoxify organic pollutants is well known. Paulownia tomentosa, instead, showed high metal removal. The Cytisus scoparius was the least effective plant in soil decontamination. The recovery of soil functionality was followed by enzyme activities, expressing the biochemical processes underway, and nutrient content useful for plant growth and development. Throughout the area, an enhancement of metabolic processes and soil chemical quality was observed. All the enzymatic activities showed a general increase over time (until 3-4 fold than the initial value for urease and beta-glucosidase). Moreover, Cytisus scoparius, even though it showed a lower decontamination capability, was the most effective in soil metabolic stimulation. PMID- 26555403 TI - Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS). AB - OBJECTIVES: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries. METHODS: From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated. RESULTS: Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjogren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4). CONCLUSIONS: Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors. PMID- 26555404 TI - Methyl-, Ethenyl-, and Ethynyl-Bridged Cationic Digold Complexes Stabilized by Coordination to a Bulky Terphenylphosphine Ligand. AB - Reactions of the gold(I) triflimide complex [Au(NTf2 )(PMe2 Ar${{^{{?rm Dipp}{_{2}}}}}$)] (1) with the gold(I) hydrocarbyl species [AuR(PMe2 Ar${{^{{?rm Dipp}{_{2}}}}}$)] (2 a-2 c) enable the isolation of hydrocarbyl-bridged cationic digold complexes with the general composition [Au2 (MU-R)(PMe2 Ar${{^{{?rm Dipp}{_{2}}}}}$)2 ][NTf2 ], where Ar${{^{{?rm Dipp}{_{2}}}}}$=C6 H3 -2,6-(C6 H3 2,6-iPr2 )2 and R=Me (3), CH?CH2 (4), or C?CH (5). Compound 3 is the first alkyl bridged digold complex to be reported and features a symmetric [Au(MU-CH3 )Au](+) core. Complexes 4 and 5 are the first species of their kind that contain simple, unsubstituted vinyl and acetylide units, respectively. In the series of complexes 3-5, the bridging carbon atom systematically changes its hybridization from sp(3) to sp(2) and sp. Concomitant with this change, and owing to variations in the nature of the bonding within the [Au(MU-R)Au](+) unit, there is a gradual decrease in aurophilicity, that is, the strength of the Au???Au bonding interaction decreases. This change is illustrated by a monotonic increase in the Au-Au distance by approximately 0.3 A from R=CH3 (2.71 A) to CH?CH2 (3.07 A) and C?CH (3.31 A). PMID- 26555405 TI - Hydroxychloroquine in Systemic Lupus Erythematosus: Comment on the Article by Muangchan et al. PMID- 26555406 TI - Salinity induces membrane structure and lipid changes in maize mesophyll and bundle sheath chloroplasts. AB - The membranes of Zea mays (maize) mesophyll cell (MC) chloroplasts are more vulnerable to salinity stress than are those of bundle sheath cell (BSC) chloroplasts. To clarify the mechanism underlying this difference in salt sensitivity, we monitored changes in the glycerolipid and fatty acid compositions of both types of chloroplast upon exposure to salinity stress. The monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) contents were higher in MC chloroplasts than in BSC chloroplasts, in both the presence and absence of salt treatment. Under salt conditions, the MGDG level in MC chloroplasts was significantly lower than under normal conditions, while it was unchanged in BSC chloroplasts. In both types of chloroplast, the contents of DGDG, phosphatidylglycerol and phosphatidylinositol remained at the same levels in control and salt-treated plants, whereas sulfoquinovosyldiacylglycerol and phosphatidylcholine were significantly lower and higher, respectively, upon salt treatment. In addition, the fatty acid composition and double bond index of individual lipid classes were changed by salt treatment in both BSC and MC chloroplasts, although these factors had no effect on glycerolipid content. These findings suggest that the difference in salt sensitivity of MC and BSC chloroplast membranes is related to differences in MGDG responses to salinity. Thus, we propose that the low MGDG content and the low sensitivity of MGDG to salinity in BSC chloroplasts render them more tolerant than MC chloroplasts to salinity stress. PMID- 26555407 TI - First Report of a Successful Pregnancy in an Everolimus-Treated Heart Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs. AB - The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy. PMID- 26555408 TI - Placental Massive Perivillous Fibrinoid Deposition Associated with Coxsackievirus A16-Report of a Case, and Review of the Literature. AB - Massive placental perivillous fibrinoid deposition in the placenta is thought to be an immune-related condition associated with poor perinatal outcomes, including growth restriction and intrauterine fetal demise, with a high risk of recurrence. Rare cases have been associated with Coxsackievirus infection. We present such a case and review the literature. PMID- 26555410 TI - [Guidelines for diagnosis and management of aneurysmal subarachnoid hemorrhage: top issues and prospective]. AB - OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is a kind of hemorrhagic stroke with high mortality and morbidity. Although the preoperative diagnosis, surgical clipping, endovascular treatment, and intensive care have progressed in recent years, the overall prognosis of aSAH patients remains poor. In 2011, the Neurocritical Care Society organized an international, multidisciplinary consensus conference addressed the critical care management of SAH. In 2012, the American Stroke Association (AHA) updated the guidelines of diagnosis and treatment of aSAH published in 2009. In 2013, European Stroke Organization established the guideline for management of intracranial aneurysms and SAH. In 2014, the Korean Society of Interventional Neuroradiology (KSIN) published clinical practice guideline for the management of ruptured and unruptured aneurysms. The guideline for diagnosis and management of aSAH for Chinese patients has been drafted in this year. Thus, the diagnosis and management of aSAH is a hot topic in neurosurgery. This editorial summarizes the above mentioned guidelines and focuses on the progress and update of these guidelines. In this article we discuss the advantage and disadvantage of those imaging techniques, the pros and cons of surgical clipping and endovascular treatment. PMID- 26555409 TI - Development of a PubMed Based Search Tool for Identifying Sex and Gender Specific Health Literature. AB - BACKGROUND: An effective literature search strategy is critical to achieving the aims of Sex and Gender Specific Health (SGSH): to understand sex and gender differences through research and to effectively incorporate the new knowledge into the clinical decision making process to benefit both male and female patients. The goal of this project was to develop and validate an SGSH literature search tool that is readily and freely available to clinical researchers and practitioners. METHODS: PubMed, a freely available search engine for the Medline database, was selected as the platform to build the SGSH literature search tool. Combinations of Medical Subject Heading terms, text words, and title words were evaluated for optimal specificity and sensitivity. The search tool was then validated against reference bases compiled for two disease states, diabetes and stroke. RESULTS: Key sex and gender terms and limits were bundled to create a search tool to facilitate PubMed SGSH literature searches. During validation, the search tool retrieved 50 of 94 (53.2%) stroke and 62 of 95 (65.3%) diabetes reference articles selected for validation. A general keyword search of stroke or diabetes combined with sex difference retrieved 33 of 94 (35.1%) stroke and 22 of 95 (23.2%) diabetes reference base articles, with lower sensitivity and specificity for SGSH content. CONCLUSIONS: The Texas Tech University Health Sciences Center SGSH PubMed Search Tool provides higher sensitivity and specificity to sex and gender specific health literature. The tool will facilitate research, clinical decision-making, and guideline development relevant to SGSH. PMID- 26555411 TI - [Prevention and treatment of drug-related stroke]. AB - Stroke classified into ischemic and hemorrhagic subtypes, is among the most devastating diseases for human being. Certain drugs could increase the blood viscosity, thereby increasing the potential risk of ischemia. Anti-platelet and anti-coagulation drugs, as the treatment of first choice, increase the risk of intracranial hemorrhage and death. Here, we are the first to propose the concept of drug-related stroke, and discuss the treatment strategy for patients who are complicated with intracranial hemorrhage or plan to receive neurosurgical operation during either anti-platelet or anti-coagulation medication. We hope to arouse the attention for drug related stroke among the clinicians and offer recommendation for clinical intervention. PMID- 26555412 TI - [Pterional keyhole approach in surgical treatment of ruptured anterior circulation intracranial aneurysm: a report of 313 cases]. AB - OBJECTIVE: To review the surgical modality with pterional keyhole approach in treatment of anterior circulation aneurysm. METHODS: Three hundred and thirteen patients with ruptured anterior circulation intracranial aneurysm treated surgically with pterional keyhole approach between January 2009 and June 2014 in Department of Neurosurgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, were included in the analysis. Complete occlusion rate of aneurysms and incidence of major complications including delayed cerebral ischemia and chronic hydrocephalus were documented. Surgical outcomes at 6-month follow up were assessed by modified Rankin Scale. RESULTS: Totally 348 aneurysms were treated with pterional keyhole approach, 326 aneurysms were completely clipped, 16 aneurysms were partly clipped, and 6 aneurysms were wrapped with gauze material. Among 313 patients, 15 patients (4.79%) suffered from delayed cerebral ischemia, and 10 patients (3.19%) suffered from hydrocephalus. At the 6 month follow up, the rate of good outcome was 66.77% (209/313). CONCLUSIONS: The pterional keyhole approach can be used to clip most of anterior circulation aneurysms, and it seems to have advantages over the traditional approaches with lower incidence of complications and similar outcomes. PMID- 26555413 TI - [Brainstem cavernous malformation and its surgical treatment]. AB - OBJECTIVE: To analyze the clinical characteristics and surgery approach for patients with brainstem cavernous malformation (BSCM). METHODS: The clinical data of 23 BSCM patients (5 cases at midbrain, 16 cases at pons, and 2 cases at medulla) treated in the Second Affiliated Hospital Zhejiang University School of Medicine from July 2003 to June 2014 were retrospectively reviewed. The medical history, radiological findings, operation records, postoperative course and follow-up results were analyzed. RESULTS: Suboccipital approach, retrosigmoid approach, subtentorial supracerebella approach, Poppen approach, pterional approach, Kawase approach, interhemispheric transcallosal third ventrical approach were applied for the surgery of BSCM patients. Among them, Kawase approach and interhemispheric transcallosal third ventrical approach were firstly reported in treatment of BSCM. Total resection was achieved in 22 cases. Neurological function was improved in 15 cases, unchanged in 7 cases and deteriorated in 1 case. Fifteen cases were followed up for a mean period of 3.5 years and signs of recurrence was found. CONCLUSION: Proper selection of surgical approach is important to assure total resection of the lesions, to protect surrounding normal vital structures and to avoid post-surgical complications. PMID- 26555414 TI - [Evacuation of spontaneous supratentorial intracerebral hematoma with double targets-single channel and multiaxial stereotaxis]. AB - OBJECTIVE: To evaluate the efficacy and safety of evacuation of spontaneous supratentorial hemorrhage with double targets-single channel and multiaxial stereotaxis. METHODS: Thirty-four patients with supratentorial intracerebral hemorrhage, who underwent hematoma evacuation with the method of double targets single channel between January 2014 and November 2014 in the Second Affiliated Hospital, Zhejiang University School of Medicine, were included in the study. We classified the hematoma into four types based on the principle of double targets single channel calculation method (DTSC). And the appropriate stereotactic surgery path and operation opportunity were designed individually according to the hematoma volume and mass effect. Twenty-seven patients with supratentorial hemorrhage who underwent hematoma evacuation with the method of single targets single channel between January 2013 and November 2014 were selected as single target group. RESULTS: Volumes of initial hematoma in DTSC and single target groups were(38.6 +/- 19.2)mL and(40.1 +/- 18.1)mL, respectively. Initial Glasgow Coma Scale were 9.6 +/- 3.2 (3~15) and 9.1 +/- 2.9(3~13) (all P >0.05). Residual volume of hematoma and clearance ratio were (11.1 +/- 4.2) mL and(73.1 +/- 5.4)% in DTSC group and (18.5 +/- 5.3) mL and(55.1 +/- 5.1)% in single target group by CT scan 24 h after operation(all P <0.05). There was no significant difference in Glasgow Outcome Scale between two groups in one-month follow-up. Average length of postoperative stay of two groups were(12.6 +/- 9.8)d and (14.2 +/- 7.1)d, respectively. CONCLUSION: Evacuation of spontaneous supratentorial intracerebral hematoma with DTSC and multi-axial stereotaxis can increase clearance ratio remarkably and decrease average length of stay. PMID- 26555415 TI - [Surgical treatment of anterior circulation aneurysms via lateral supraorbital approach]. AB - OBJECTIVE: To evaluate the efficacy of the surgery with lateral supraorbital approach for clipping anterior circulation aneurysms. METHODS: The clinical data of 99 patients with anterior circulation aneurysms who underwent a clipping via lateral supraorbital approach from October 2012 to September 2014 and 75 patients, who underwent a clipping via pterional approach from January 2010 to December 2011 in the second Affiliated Hospital, Zhejiang University School of Medicine were reviewed. The operative duration, prognosis, residual rate and rupture rate during surgery were compared between two groups. RESULTS: The patients by lateral supraorbital approach had a shorter operative duration, namely 37~61 min less than that in the patients by pterional approach. No difference were found in residual rate and rupture rate between two groups. The Glasgow Outcome Scale (GOS) at 3 months after surgery showed no significant difference between two groups. CONCLUSION: The lateral supraorbital approach can be used safely and effectively with shorter operative duration and less tissue damage for treatment of patients with anterior circulation aneurysms. PMID- 26555416 TI - [Comparison clinical efficacy of 3% hypertonic saline solution with 20% mannitol in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage]. AB - OBJECTIVE: To compare the efficacy of 3% hypertonic saline solution with 20% mannitol in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage. METHODS: An alternating treatment protocol was used to compare the efficacy of 160 mL 3% hypertonic saline solution (HSS) with 150 mL 20% mannitol for episodes of increased intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage. The dependent variables were the extent and duration of reduction of increased ICP after each event. RESULTS: Both 3% HSS and 20% mannitol rapidly decreased the ICP in patients with aneurysmal subarachnoid hemorrhage (P <0.01). No difference between two medications in the extent of duration of ICP and reduction of action (P >0.05). CONCLUSION: 3% HSS should be considered as the first-line osmotic drug in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage. PMID- 26555417 TI - [A3-A3 side-to-side anastomosis combined with endovascular intervention in recurrent complex anterior artery aneurysm: a case report and literature review]. AB - A 28-year-old female patient was admitted to the Second Affiliated Hospital, Zhejiang University School of Medicine, with sudden headache and vomiting for 1 day. CT scan conducted at emergency revealed subarachnoid hemorrhage, whereas digital subtraction angiography demonstrated a wide-neck aneurysm located at A1 segment of the left anterior cerebral artery. The aneurysm was totally coiled using stent assistance, which, however, was recanalized at 3 month follow-up. This patient was then subjected to aneurysm and parent artery occlusion after bypass of the bilateral A3 segments, who recovered well and discharged without ischemic complications. PMID- 26555418 TI - [Effects of miRNA-21 on paclitaxel-resistance in human breast cancer cells]. AB - OBJECTIVE: To investigate the effects of miR-21 on paclitaxel-resistance in human breast cancer MCF-7/PR and SKBR-3/PR cells. METHODS: Paclitaxel-resistant human breast cancer cell lines MCF-7/PR and SKBR-3/PR were established by stepwise selection in increasing concentration of paclitaxel. Cellular morphology, mRNA and protein level of MDR1, BCRP and MRP1 in MCF-7/PR and SKBR-3/PR cells were determined. The expression of Bax, Bcl-2 and miR-21 in parental and paclitaxel resistant cells was detected by RT-PCR and Western blotting. The synthetic miR-21 inhibitor or miR-21 mimic were transfected into MCF-7/PR, SKBR-3/PR and MCF-7, SKBR-3 cells with Lipofectamine 2000. The miR-21 levels were determined by RT PCR, and P-gp, Bcl-2 and Bax protein levels were examined by Western blotting. MTT assay was used to measure the cell viability, and flow cytometry was performed to analyze the cell cycle and apoptosis. RESULTS: The levels of MDR1, BCRP, MRP1, Bcl-2/Bax and miR-21 in MCF-7/PR and SKBR-3/PR cells were significantly higher than those in MCF-7 and SKBR-3 cells. The protein levels of P-gp, Bcl-2 were up-regulated, and Bax was down-regulated compared with parental cells. MiR-21 was significantly down-regulated after miR-21 inhibitor was transfected; and the levels of MDR1, BCRP, MRP1 and Bcl-2/Bax (P <0.05) were also down-regulated. MiR-21 inhibitors significantly suppressed G0/G1 transition of the cell cycle, and induced cell apoptosis in MCF-7/PR and SKBR-3/PR cells. MTT results showed that miR-21 inhibitors induced sensitivity of MCF-7/PR and SKBR 3/PR cells to paclitaxel. And miR-21 mimic can increase the expression of MDR1, Bcl-2/Bax and change cell morphology from parental cells to resistant cells. RESULTS: The established MCF-7/PR and SKBR-3/PR breast cancer cells show typical multidrug resistance characteristics, which can be used as the model for drug resistance study. Down-regulated miR-21 expression in MCF-7/PR and SKBR-3/PR breast cancer cells can enhance cell sensitivity to paclitaxel. PMID- 26555419 TI - [Risk factors of progressive brain contusion and relationship with outcome]. AB - OBJECTIVE: To investigate the risk factors of progressive brain contusion and to evaluate their impact on patients' outcome. METHODS: One hundred and thirty two patients with traumatic brain contusion were enrolled in the study, including 70 cases with progressive contusion and 62 cases with non-progressive contusion. The risk factors were investigated with univariate and multivariate Logistic regression analysis. RESULTS: The univariate analysis showed that Glasgow Coma Score (GCS) at admission, contusion volume at the first brain CT scans, midline shift, combined with skull fracture, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, location of brain contusion, D-dimer levels, combined with type 2 diabetes were associated with progressive brain contusion. Multivariate Logistic regression analysis showed that GCS at admission, contusion volume at the first CT scans, combined with subarachnoid hemorrhage, combined with type 2 diabetes were the independent risk factors for disease progression. The outcome in the progressive group was more aggravated than that in non-progressive group (P = 0.001). CONCLUSION: Patients with disturbance of consciousness, the larger contusion volume, combined with subarachnoid hemorrhage and diabetes are at risk for progressive brain contusion and unfavorable outcome. PMID- 26555420 TI - [Distribution of HCV genotypes in Chinese Han population with chronic hepatitis C]. AB - OBJECTIVE: To investigate the distribution of HCV genotypes in Chinese Han population with chronic hepatitis C (CHC). METHODS: This randomized multicenter study included 1 014 CHC patients from 28 hospitals in different regions of China. SPSS 20.0 was applied to analyze the relationship among region, HCV genotype, gender and the replication level of HCV-RNA. RESULTS: HCV 1 genotype (56.80%) was the most common genotype. The majority of CHC patients were of genotype 1, 2, 3, 6 in the order of frequency, except those in southwestern, southern and central China. HCV 1, 2, 3, 6 genotypes were most common among male patients in southern China; among female patients in northern China; among male patients in northern and northwestern China and among male patients in northwestern China, respectively (all P <0.05). There was no statistical significance between different genders in other regions. The high viral load was more common than the low viral load among HCV 1, 2, 3, 6 genotype-infected patients. CONCLUSION: There are different distributions of HCV genotypes among the different regions. In addition, HCV genotypes are correlated with gender and HCV-RNA load. PMID- 26555421 TI - [Preparation of rabbit monoclonal antibody against cGMP and development of competitive ELISA for cGMP]. AB - OBJECTIVE: To prepare rabbit monoclonal antibody (RabMab) against guanosine 3', 5'-cyclic monophosphate (cGMP) and to develop a competitive ELISA for the detection of cGMP. METHODS: New Zealand white rabbits were immunized with synthesized cGMP-keyhole limpet hemoeyanin (cGMP-KLH) to prepared a RabMAb with monoclonal antibody technique of Epitomics. A competitive ELISA kit was produced with cGMP RabMAb. The specificity, the precision and the recoveries of the method were determined. RESULTS: The RabMAb with high sensitivity towards cGMP were prepared with an antibody timer of 3.1 ng/mL and 50% inhibitive concentration (IC50) of 12.57 ng/mL. The cGMP RabMAb had 33% cross-reactivity to inosine 3', 5' cyclic monophosphate (cIMP) and little or no cross-reactivity to other compounds. A competitive ELISA was developed for detection of cGMP. The range of detection was 0~120 ng/mL with a minimal limit of 1.95 ng/mL. The recovery of assay was 89%~103%. The inter-assay and intra-assay coefficient variations were below 11.68% and 13.85%, respectively. CONCLUSION: The RabMab against cGMP with high affinity and high specificity has been generated successfully, and a competitive ELISA for detection of cGMP has been developed with the prepared cGMP RabMAb. PMID- 26555422 TI - [Simultaneous quantitative analysis of different ceramide species in cells by high-performance liquid chromatography-tandem mass spectrometry]. AB - OBJECTIVE: To establish a high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS) method for simultaneous quantitative analysis of different ceramide species in cells. METHODS: The analysis was performed on an Agilent 1290 HPLC system with a ZORBAX Eclipse XDB-C8 (150.0 mm * 2.1 mm, 3.5 MUL) column and a temperature of 35 C. Methanol with 1 mmol/L ammonium formate and 0.2% formic acid was used as mobile phase A and 100% methanol was used as mobile phase B. And the ceramides were separated by gradient elution at a flow rate of 0.3 mL/min. Electrospray ionization (ESI) with multiple reaction monitoring (MRM) was used in the analysis. RESULTS: Four ceramide species all had a good linear response in the determination ranges (R2 >= 0.9987). The average recoveries (n = 9) were 99.1%,99.9%,100.5% and 98.2% with RSDs of 5.6%, 5.1%, 4.7% and 5.5%, respectively. In addition, the levels of ceramides in FL cells were relatively stable, while the C24-ceramide had the highest level. CONCLUSION: The HPLC-ESI-MS method for simultaneous analysis of ceramides has high accuracy, reproducibility and linearity, which may be used for quantification of ceramide species in cells. PMID- 26555423 TI - [The value of narrow-band imaging with magnifying endoscopy in diagnosis of early gastric cancer: a meta-analysis]. AB - OBJECTIVE: To assess the diagnostic value of narrow-band imaging with magnifying endoscopy (NBI-ME) for early gastric cancer (EGC). METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for literature of NBI-ME in diagnosis of EGC, and then performed meta-analysis. RESULTS: A total of 12 articles involving 2 278 samples from 2 048 patients were included. The overall sensitivity of NBI-ME for diagnosis of EGC was 0.84 [95% CI: 0.80~0.87], specificity was 0.96 (95% CI: 0.95~0.97),and area under the symmetric receiver operator characteristic curve (AUC) was 0.9592. The AUC value of the NBI-ME plus conventional white light endoscopy (C-WLE) subgroup (0.9706) was higher than that of NBI-ME alone (0.8162). The incremental yield of NBI-ME plus C-WLE over C-WLE was significant (IY = 9.4%, P = 0.011), while NBI-ME alone over C-WLE was not significant (IY = 0.8%, P = 0.498). CONCLUSIONS: The results show that NBI-ME plus C-WLE is an effective and preferable method for diagnosis of EGC; however, NBI-ME alone is not superior to C-WLE. PMID- 26555424 TI - [Epidemiology, diagnosis and treatment of Middle East respiratory syndrome]. AB - Middle East respiratory syndrome (MERS) has raised global public health concerns. The recent outbreak of MERS coronavirus (MERS-CoV) infection has led to 1 338 laboratory-confirmed cases in 26 countries worldwide as reported till 19 June, 2015. MERS-CoV may be considered a zoonotic virus that has crossed the species barrier to humans, but the pathogenesis and the routes of transmission are not completely understood. Most MERS-CoV cases reported thus far have a history of residence in or travel to the Middle East. Human-to-human transmission though was observed on some occasions in Korea, it is documented as non-sustainable event. The envelope spike glycoprotein on the surface of MERS-CoV which mediates receptor binding, membrane fusion and viral entry is thought to be involved in the mechanism of MERS-CoV.No specific and effective treatment for MERS-CoV is currently recommended, although supportive treatment has played an important role. Prophylactic strategies are necessary to prevent MERS-CoV infection. PMID- 26555425 TI - [Progress on perioperative monitoring of cerebral blood flow autoregulation]. AB - Cerebral blood flow autoregulation is physiologically protective mechanism to maintain the stability of cerebral blood flow. Once autoregulation is impaired, the cerebral blood flow fluctuates with blood pressure, leading to the risk of brain ischemia or cerebral hyperemia. Multiple research results indicate that cerebral blood flow can be monitored indirectly and continuously with transcranial Doppler, near infrared spectroscopy or ICP. The correlation coefficient calculated by the surrogate for cerebral blood flow and blood pressure is used to judge cerebral blood flow autoregulation. When the correlation coefficient is close to 1, cerebral blood flow will be passively fluctuated by blood pressure, indicating autoregulation is impaired. When the coefficient is less than 0, cerebral blood flow will not be changed with blood pressure, indicating autoregulaiton is intact. The status of autoregualtion is closely associated with mortality or poor neurological outcomes in patients with cardiac surgery underwent cardiopulmonary bypass, liver transplantation patients or patients with deep trendelenburg position for long time or beach chair position. Continuous monitoring of cerebral blood flow autoregulation can identify the lower or the upper limit of autoregulation, and provide information to individualize the perioperative management of blood pressure. PMID- 26555426 TI - [Advances in measles virus for cancer therapy]. AB - Oncolytic virotherapy is a novel cancer therapy. Vaccine-attenuated strains of measles virus(MV)is an ideal candidate for oncolytic virotherapy which has an excellent safety record. Vaccine-attenuated MV uses CD46 and Nectin-4 molecule as major entry receptors into cells. Vaccine-attenuated MV can selectively infect and kill a wide variety of cancer cells in vitro and in vivo. With the development of molecular cloning, scientists have successfully rescued cDNA of vaccine-attenuated MV and increased its oncolytic efficiency with molecular engineering techniques. Phase I clinical trials of virotherapy for ovarian cancer and multiple myeloma with vaccine-attenuated MV are underway. The preliminary results indicate the promising antitumor potential of vaccine-attenuated MV. PMID- 26555427 TI - [Asteatotic dermatitis: etiology and pathogenesis]. AB - Asteatotic dermatitis (AsD) is a common skin disease characterized by dry skin, itching, erythema, peeling and other skin lesions. It results from the damage in cutaneous barrier related to age, seasonal climate and bathing habits, and presents dysfunction of sebaceous, sweat glands and the increase of transepidermal water loss. The pathogenesis of AsD is not clear. Previous studies mainly focused on the relationship between skin barrier damage and bathing habits, age or gender. Recently, more studies focus on its relationship with other systematic diseases and drugs. This paper reviews etiology and pathogenesis of AsD to provide new ideas for the diagnosis and treatment of AsD. PMID- 26555428 TI - Intensity of anxiety is modified via complex integrative stress circuitries. AB - Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of alpha2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic alpha2 adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and alpha2 adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom. PMID- 26555429 TI - MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice. AB - Depressive disorders have complex and multi-faceted underlying mechanisms, rendering these disorders difficult to treat consistently and effectively. One under-explored therapeutic strategy for alleviating mood disorders is the targeting of microRNAs (miRs). miRs are small non-coding RNAs that cause sequestration/degradation of specific mRNAs, thereby preventing protein translation and downstream functions. miR-155 has validated and predicted neurotrophic factor and inflammatory mRNA targets, which led to our hypothesis that miR-155 deletion would modulate affective behaviors. To evaluate anxiety like behavior, wildtype (wt) and miR-155 knockout (ko) mice (littermates; both male and female) were assessed in the open field and on an elevated plus maze. In both tests, miR-155 ko mice spent more time in open areas, suggesting they had reduced anxiety-like behavior. Depressive-like behaviors were assessed using the forced swim test. Compared to wt mice, miR-155 ko mice exhibited reduced float duration and increased latency to float. Further, although all mice exhibited a strong preference for a sucrose solution over water, this preference was enhanced in miR-155 ko mice. miR-155 ko mice had no deficiencies in learning and memory (Barnes maze) or social preference/novelty suggesting that changes in mood were specific. Finally, compared to wt hippocampi, miR-155 ko hippocampi had a reduced inflammatory signature (e.g., decreased IL-6, TNF-a) and female miR-155 ko mice increased ciliary neurotrophic factor expression. Together, these data highlight the importance of studying microRNAs in the context of anxiety and depression and identify miR-155 as a novel potential therapeutic target for improving mood disorders. PMID- 26555430 TI - Cortisol levels and suicidal behavior: A meta-analysis. AB - Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. This meta-analytic review aimed (i) to estimate the strength and variability of the association between naturally fluctuating cortisol levels and suicidal behavior and (ii) to identify moderators of this relationship. A systematic literature search identified 27 studies (N=2226; 779 suicide attempters and 1447 non-attempters) that met the study eligibility criteria from a total of 417 unique records initially examined. Estimates of effect sizes (r) obtained from these studies were analysed using Comprehensive Meta-Analysis. In these analyses, we compared participants identified as having a past history of suicide attempt(s) to those with no such history. Study quality, mean age of sample and percentage of male participants were examined as potential moderators. Overall, there was no significant effect of suicide group on cortisol. However, significant associations between cortisol and suicide attempts were observed as a function of age. In studies where the mean age of the sample was below 40 years the association was positive (i.e., higher cortisol was associated with suicide attempts; r=.234, p<.001), and where the mean age was 40 or above the association was negative (i.e., lower cortisol was associated with suicide attempts; r=-.129, p<.001). These findings confirm that HPA axis activity, as indicated by age-dependent variations in cortisol levels, is associated with suicidal behavior. The challenge for theory and clinical practice is to explain the complete reversal of the association with age and to identify its clinical implications. PMID- 26555432 TI - Correction: Increased Wounding of Southern Right Whale (Eubalaena australis) Calves by Kelp Gulls (Larus dominicanus) at Peninsula Valdes, Argentina. PMID- 26555431 TI - Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor alpha agents, a retrospective cohort study. AB - INTRODUCTION: Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFalpha) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors). METHODS: RA patients at least 18 years old were selected from the MarketScan databases (2010-2012) if they had at least one prescription/administration of abatacept, rituximab, tocilizumab, or anti-TNF after having discontinued a different biologic agent and meeting enrollment criteria. Cox models estimated the risk of incident ILD and ILD-related hospitalization. Sensitivity analyses used an alternate ILD case definition. RESULTS: We identified 13,795 episodes of biologic exposure in 11,219 patients. Mean (standard deviation) follow-up was 0.7 (0.5) years. Patients receiving alternate MOA agents were more likely to have had recent exposure to steroids, prior exposure to a greater number of biologics, and history of ILD, anemia, chronic obstructive pulmonary disease, and other pulmonary conditions. When the sensitive definition was used, unadjusted ILD incidence rates (95% confidence interval, or CI) ranged from 4.0 (1.6-8.2, abatacept) to 12.2 (5.6 23.2, infliximab) per 1000 person-years. Being older (hazard ratio (HR) 3.5; 95% CI 2.1-6.0), being male (HR 3.1; 95% CI 1.2-8.4), and having another pulmonary condition (HR 4.8; 95% CI 1.7-13.7) were associated with increased ILD incidence in either sensitive and/or specific models. There were no significant differences by biologic class. Hospitalization rates (95% CI) when the sensitive definition was used ranged from 55.6 (6.7-200.7, tocilizumab) to 262.5 (71.5-672.2, infliximab). In Cox models, recent methotrexate exposure was associated with reduced ILD hospitalization (HR 0.16; 95% CI 0.06-0.46), whereas being male (HR 2.5; 95% CI 1.3-4.8) and having had a hospitalization for asthma (HR 3.4; 95% CI 1.2-9.8) or ILD/pneumonia (HR 2.3; 95% CI 1.1-4.7) in the 12 months prior to index were associated with increased hospitalization risk. CONCLUSIONS: There were no significant differences in the risk of ILD and its related complications between RA patients receiving anti-TNFalpha agents and those receiving alternate MOA agents. Further studies are needed that account for differences in baseline characteristics in order to fully evaluate the risk of ILD and its complications. PMID- 26555433 TI - Atresia of the common pulmonary vein: the importance of phenotypic recognition. PMID- 26555434 TI - Prevalence of pain-related single nucleotide polymorphisms in patients of African origin with sickle cell disease. AB - BACKGROUND: Prospective pain genetics research is hindered by a lack of data on the prevalence of polymorphisms in pain-relevant genes for patients with sickle cell disease (SCD). For African-Americans in general, limited information is available in public databases. METHODS: We prioritized and examined the genotype and allele frequencies of 115 SNPs from 49 candidate pain genes in 199 adult African-Americans and pediatric patients of African origin with SCD. Analyses were performed and compared with available data from public databases. RESULTS: Genotype and allele frequencies of a number of SNPs were found to be different between our cohort and those from the databases and between adult and pediatric subjects. CONCLUSION: As pain therapy is inadequate in a significant percentage of patients with SCD, candidate pain genetic studies may aid in designing precision pain medicine. We provide prevalence data as a reference for prospective genetic studies in this population. PMID- 26555435 TI - Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells. AB - Patient derived xenograft (PDX) models are gaining popularity in cancer research and are used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. Circulating tumor cells (CTC) play a critical role in tumor metastasis and have been isolated from patients with several tumor types. Recently, CTCs have been used to generate PDX experimental models of breast and prostate cancer. This manuscript details the method for the generation of prostate cancer PDX models from CTCs developed by our group. Advantages of this method over conventional PDX models include independence from surgical sample collection and generating experimental models at various disease stages. Density gradient centrifugation followed by red blood cell lysis and flow cytometry depletion of CD45 positive mononuclear cells is used to enrich CTCs from peripheral blood samples collected from patients with metastatic disease. The CTCs are then injected into immunocompromised mice; subsequently generated xenografts can be used for functional studies or harvested for molecular characterization. The primary limitation of this method is the negative selection method used for CTC enrichment. Despite this limitation, the generation of PDX models from CTCs provides a novel experimental model to be applied to prostate cancer research. PMID- 26555436 TI - A colorimetric probe to determine Pb(2+) using functionalized silver nanoparticles. AB - A simple and sensitive colorimetric method for the determination of Pb(2+) ions in aqueous samples was developed using 1-(2-mercaptoethyl)-1,3,5-triazinane-2,4,6 trione (MTT) functionalized silver nanoparticles (MTT-AgNPs). The Pb(2+) ion acted as the metal center of the coordination complex, which formed N-Pb(2+)-O coordination bonds with the MTT-AgNPs, shortening the interparticle distance, and inducing aggregation of the MTT-AgNPs. This aggregation resulted in a dramatic color change from yellow to dark blue. Using this methodology, the concentration of Pb(2+) ions in environmental samples could be quantitatively detected with the naked eye or by using UV-vis spectrometry. Also, we found that the selectivity and sensitivity of detection were noticeably improved in the pH range of 7-8, at which a more obvious color change was observed. The absorption ratios (A625/A395) of the modified AgNP solution exhibited a linear correlation with Pb(2+) ion concentrations within the linear range of 0.1-0.6 MUg mL(-1), and the limits of detection in tap and pond water were 0.02 and 0.06 MUg mL(-1), respectively. This cost-effective sensing system allows for the rapid and facile determination of Pb(2+) ions in aqueous samples. PMID- 26555437 TI - The prevalence of CALR mutations in a cohort of patients with myeloproliferative neoplasms. AB - INTRODUCTION: To investigate the prevalence of calreticulin (CALR) mutations in JAK2- and MPL-non-mutated patients with suspected myeloproliferative neoplasm (MPN) from a large MPN clinic and confirm a diagnosis of MPN. METHODS: JAK2/MPL non-mutated patients from the Belfast City Hospital (BCH) with either of the MPNs - ET or MF - and diagnosed between 1988 and 2014 were selected for CALR screen. All cases were validated according to the WHO 2008 classification for MPNs. Statistical analysis was performed with Minitab 16 Statistical Software package. Exon 9 of CALR was amplified by PCR using genomic DNA, and mutations were detected by fragment analysis. RESULTS: Of the 62 JAK2/MPL-non-mutated MPN patients screened, 57 had ET and 5 had MF; 34 patients (53.1%) carried CALR mutations. Three of 5 MF patients were CALR positive. Thirty-one ET patients (54.3%) harboured CALR mutation, whereas 26 (45.7%) were classified as 'triple negatives'. CONCLUSION: Detection of CALR mutations in a cohort of JAK2/MPL-non mutated patients with suspected MPN confirmed the diagnosis of MPN in around 53% of cases. This is lower than initially reported, but similar to subsequent studies. However, a sizable cohort of patients remains lacking a specific molecular marker. PMID- 26555438 TI - Bifunctional Sphingosine for Cell-Based Analysis of Protein-Sphingolipid Interactions. AB - Sphingolipids are essential structural components of cellular membranes and are crucial regulators of cellular processes. While current high-throughput approaches allow for the systematic mapping of interactions of soluble proteins with their lipid-binding partners, photo-cross-linking is the only technique that enables for the proteome-wide mapping of integral membrane proteins with their direct lipid environment. Here, we report the synthesis of a photoactivatable and clickable analog of sphingosine (pacSph). When administered to sphingosine-1 phosphate lyase deficient cells, pacSph allows its metabolic fate and the subcellular flux of de novo synthesized sphingolipids to be followed in a time resolved manner. The chemoproteomic profiling yielded over 180 novel sphingolipid binding proteins, of which we validated a number, demonstrating the unique value of this technique as a discovery tool. This work provides an important resource for the understanding of the global cellular interplay between sphingolipids and their interacting proteins. PMID- 26555439 TI - Supramolecular Alternating Polymer from Crown Ether and Pillar[5]arene-Based Double Molecular Recognition for Preparation of Hierarchical Materials. AB - A novel supramolecular alternating polymer is constructed based on double molecular recognition events of benzo-21-crown-7 with a secondary ammonium salt and of pillar[5]arene with a neutral guest. The resulting polymer is utilized to prepare hierarchical materials with different dimensionalities for the first time. These materials included zero-dimensional spherical aggregates, one dimensional nanofibers, two-dimensional microstructured films, and three dimensional ordered glue. This development will be helpful for designing and preparing supramolecular hierarchical materials with different dimensionalities. PMID- 26555440 TI - Pulse pressure is not an independent predictor of incident atrial fibrillation in 60-year-old men and women. AB - AIM: To evaluate if pulse pressure (PP) is a risk predictor for atrial fibrillation (AF) in a longitudinal study of 60-year-old men and women from Stockholm (n = 4,232), free from AF at baseline, with primary end-point incident AF. METHODS: AF diagnoses were obtained from the national hospital discharge register. The estimated risk of AF associated with increasing PP values was calculated according to PP values above median (>52.5 mmHg) and according to 1-SD increase (14 mmHg) in PP, using a crude and an adjusted Cox proportional hazard regression model. RESULTS: During a mean follow-up of 13.6 years, 286 incident AF cases were recorded. The number of AF cases increased significantly with increasing PP quartile in men but not in women. PP values above median were associated with increased AF risk (crude HR 1.63, 95% CI 1.28-2.06; p < 0.001), but risk estimates were attenuated after adjustment for common AF risk factors. When PP was entered in the Cox regression model as a continuous variable, the risk of AF did not change by 1-SD PP increase (adjusted HR 1.04, 95% CI 0.91 1.20; p = 0.560). CONCLUSIONS: PP seems not to be associated with incident AF in a Swedish population of 60-year-old men and women. PMID- 26555441 TI - PharmDB-K: Integrated Bio-Pharmacological Network Database for Traditional Korean Medicine. AB - Despite the growing attention given to Traditional Medicine (TM) worldwide, there is no well-known, publicly available, integrated bio-pharmacological Traditional Korean Medicine (TKM) database for researchers in drug discovery. In this study, we have constructed PharmDB-K, which offers comprehensive information relating to TKM-associated drugs (compound), disease indication, and protein relationships. To explore the underlying molecular interaction of TKM, we integrated fourteen different databases, six Pharmacopoeias, and literature, and established a massive bio-pharmacological network for TKM and experimentally validated some cases predicted from the PharmDB-K analyses. Currently, PharmDB-K contains information about 262 TKMs, 7,815 drugs, 3,721 diseases, 32,373 proteins, and 1,887 side effects. One of the unique sets of information in PharmDB-K includes 400 indicator compounds used for standardization of herbal medicine. Furthermore, we are operating PharmDB-K via phExplorer (a network visualization software) and BioMart (a data federation framework) for convenient search and analysis of the TKM network. Database URL: http://pharmdb-k.org, http://biomart.i-pharm.org. PMID- 26555442 TI - Total Syntheses of Perenniporides. AB - The total syntheses of perenniporide A (1) and related compounds have been achieved. Starting from 1,3,5-trifluorobenzene (9), difluorodienone 6 was obtained by oxidative dearomatization, which served as a platform for the high pressure cycloaddition and for the introduction of the C3-methoxy group. The synthesis allowed access to the natural congeners 2 and 3, enabling assignment of the absolute structures of these natural products. PMID- 26555443 TI - Why Wait? Early Determinants of School Dropout in Preventive Pediatric Primary Care. AB - BACKGROUND: To answer the question of what bio-psychosocial determinants in infancy, early and middle childhood, and adolescence predict school drop-out in young adulthood, we approached the complex process towards school dropout as a multidimensional, life-course phenomenon. The aim is to find signs of heightened risks of school dropout as early as possible which will eventually help public health workers in reducing these risks. METHODS: In a case-control design, we used data from both the Preventive Pediatric Primary Care (PPPC) files (that contain information from birth onwards) and additional questionnaires filled out by 529 youngsters, aged 18-23 years, and living in the South-east of the Netherlands. We first conducted univariate logistic regression analyses with school-dropout as the dependent variable. Backward and forward stepwise analyses with the significant variables were done with variables pertaining to the 0 to 4 year period. Remaining significant variables were forced into the next model and subsequently variables pertaining to respectively the 4 to 8, 8 to 12 and 12 to 16 year period were introduced in a stepwise analysis. All analyses were cross validated in an exploratory and confirmatory random half of the sample. RESULTS: One parent families and families with a non-Western background less often attended the health examinations of the PPPC and such less attendance was related to school dropout. The birth of a sibling (OR 0.63, 95% CI 0.43-0.93) in infancy and self-efficacy (OR 0.53, 95% CI 0.38-0.74) in adolescence decreased the odds of school dropout; externalizing behavior (OR 2.81, 95% CI 1.53-5.14) in middle childhood and (sickness) absence (OR 5.62, 95% CI 2.18-14.52) in adolescence increased the risks. CONCLUSION: To prevent school dropout, PPPC professionals should not wait until imminent dropout, but should identify and tackle risk factors as early as possible and actively approach youngsters who withdraw from public health care. PMID- 26555444 TI - RNA Thermodynamic Structural Entropy. AB - Conformational entropy for atomic-level, three dimensional biomolecules is known experimentally to play an important role in protein-ligand discrimination, yet reliable computation of entropy remains a difficult problem. Here we describe the first two accurate and efficient algorithms to compute the conformational entropy for RNA secondary structures, with respect to the Turner energy model, where free energy parameters are determined from UV absorption experiments. An algorithm to compute the derivational entropy for RNA secondary structures had previously been introduced, using stochastic context free grammars (SCFGs). However, the numerical value of derivational entropy depends heavily on the chosen context free grammar and on the training set used to estimate rule probabilities. Using data from the Rfam database, we determine that both of our thermodynamic methods, which agree in numerical value, are substantially faster than the SCFG method. Thermodynamic structural entropy is much smaller than derivational entropy, and the correlation between length-normalized thermodynamic entropy and derivational entropy is moderately weak to poor. In applications, we plot the structural entropy as a function of temperature for known thermoswitches, such as the repression of heat shock gene expression (ROSE) element, we determine that the correlation between hammerhead ribozyme cleavage activity and total free energy is improved by including an additional free energy term arising from conformational entropy, and we plot the structural entropy of windows of the HIV 1 genome. Our software RNAentropy can compute structural entropy for any user specified temperature, and supports both the Turner'99 and Turner'04 energy parameters. It follows that RNAentropy is state-of-the-art software to compute RNA secondary structure conformational entropy. Source code is available at https://github.com/clotelab/RNAentropy/; a full web server is available at http://bioinformatics.bc.edu/clotelab/RNAentropy, including source code and ancillary programs. PMID- 26555445 TI - Disease Burden of Invasive Listeriosis and Molecular Characterization of Clinical Isolates in Taiwan, 2000-2013. AB - The information about disease burden and epidemiology of invasive listeriosis in Asia is scarce. From 2000 to 2013, a total of 338 patients with invasive listeriosis (bacteremia, meningitis, and peritonitis) were treated at four medical centers in Taiwan. The incidence (per 10,000 admissions) of invasive listeriosis increased significantly during the 14-year period among the four centers (0.15 in 2000 and >1.25 during 2010-2012) and at each of the four medical centers. Among these patients, 45.9% were elderly (>65 years old) and 3.3% were less than one year of age. More than one-third (36.7%) of the patients acquired invasive listeriosis in the spring (April to June). Among the 132 preserved Listeria monocytogenes isolates analyzed, the most frequently isolated PCR serogroup-sequence type (ST) was IIb-ST87 (23.5%), followed by IIa-ST378 (19.7%) and IIa-ST155 (12.1%). Isolation of PCR serogroups IIb and IVb increased significantly with year, with a predominance of IIb-ST87 isolates (23.5%) and IIb ST 228 isolates emerging in 2013. A total of 12 different randomly amplified polymorphic DNA (RAPD) patterns (Patterns I to XII) were identified among the 112 L. monocytogenes isolates belonging to eight main PCR serogroup-STs. Identical RAPD patterns were found among the isolates exhibiting the same PCR serogroup-ST. In conclusion, our study revealed that during 2000-2013, listeriosis at four medical centers in Taiwan was caused by heterogeneous strains and that the upsurge in incidence beginning in 2005 was caused by at least two predominant clones. PMID- 26555446 TI - Response to 'Letter to "Uterine perforation in an adolescent using an intrauterine device with memory function: A case report and review of the published work"'. PMID- 26555447 TI - Duration of Expulsive Efforts and Risk of Postpartum Hemorrhage in Nulliparous Women: A Population-Based Study. AB - OBJECTIVE: To assess the specific association between the duration of expulsive efforts and the risk of postpartum hemorrhage. METHODS: Population-based cohort nested case-control study of nulliparous women delivering vaginally in 106 French maternity units between December 2004 and November 2006, including 3,852 women with PPH (blood loss >= 500 mL and/or peripartum Hb decrease >= 2 g/dL), 1,048 of them severe (peripartum Hb decrease >= 4 g/dL or transfusion of >= 2 units of red blood cells), and 762 controls from a representative sample of deliveries without hemorrhage in the same population. The association between duration of expulsive efforts and postpartum hemorrhage was estimated by multilevel logistic regression models adjusted for individual and hospital characteristics. RESULTS: Median duration of expulsive efforts was 18 minutes among controls, 20 minutes among postpartum hemorrhage and 23 minutes among severe postpartum hemorrhage (p<0.01). Duration of expulsive efforts was significantly, positively, and linearly associated with both postpartum hemorrhage and severe postpartum hemorrhage. After adjustment for other risk factors, every additional 10 minutes of expulsive efforts was associated with about a 10% increase in the risk of postpartum hemorrhage (aOR = 1.11 [1.02-1.21]) and severe postpartum hemorrhage (aOR = 1.14 [1.03-1.27]). Oxytocin during labor, duration of active phase of labor, forceps use, episiotomy, perineal tears, and birth weight were also independently associated with both risks. CONCLUSION: Duration of expulsive efforts was independently associated with postpartum hemorrhage and severe postpartum hemorrhage. Interventions to shorten the duration of this stage, such as oxytocin, forceps, and episiotomy, are also associated with higher risks of postpartum hemorrhage. Beyond duration, other aspects of the management of active second stage should be evaluated as some might allow it to last longer with a minimal increase in postpartum hemorrhage risk. PMID- 26555448 TI - Pediatric vasculitis. AB - PURPOSE OF REVIEW: The aim of this review is to define childhood vasculitis and to highlight new causative factors and treatment modalities under the guidance of recently published studies. RECENT FINDINGS: Childhood vasculitis is difficult to diagnose because of the wide variation in the symptoms and signs. New nomenclature and classification criteria were proposed for the diagnosis of pediatric vasculitis. Recently, progress has been made toward understanding the genetic susceptibility to pediatric vasculitis as it was in other diseases. Various radiological techniques provide great opportunities in establishing the diagnosis of pediatric vasculitis. Mild central nervous system disease can accompany Henoch-Schonlein purpura and can go unnoticed. Antineutrophilic cytoplasmic antibody-associated vasculitis is rare in children. Increased severity of the disease, subglottic stenosis, and renal disease are described more frequently among children. Biological therapies are used with success in children as in adults. Future studies, whose aims are to evaluate treatment responses, prognosis and to design guidelines for activity, and damage index of vasculitis for children are required. SUMMARY: Henoch-Schonlein purpura and Kawasaki disease are the most frequent vasculitides of children. Experience from adult studies for treatment and prognosis are usually used because of low incidence of other vasculitides in children. Multicenter studies of pediatric vasculitis should be conducted to detail treatment responses and prognosis in children. PMID- 26555449 TI - Diagnosis and/or classification of vasculitis: different? AB - PURPOSE OF REVIEW: Currently, there are no diagnostic criteria for vasculitides. To this end, there is a current European League Against Rheumatism and American College of Rheumatology initiative for formulating separate classification and diagnostic criteria for different forms of vasculitis. The authors of this review previously disagreed to separate classification and diagnostic criteria. They now expand this disagreement in light of both of more recent information and a reassessment of older communications. RECENT FINDINGS: We still can find no clear methodologies proposed to prepare separate diagnostic and classification criteria. Furthermore, the inadequate importance given to probabilities in discussing disease criteria was strikingly apparent. Among 77 articles on diagnostic/classification criteria making, not more than 4% discussed Bayes' theorem or predictive values or confidence intervals. The misconceptions related to the worry about circularity and the proper role of nomenclature in classification and diagnostic criteria continue. SUMMARY: Separate diagnostic and classification criteria are unrealistic. Classification criteria and nomenclature are only tools to a proper diagnosis, essentially not different for patient care or research. A frank discussion of probabilities in diagnosis is essential not only with the patients but also with all the stakeholders. PMID- 26555450 TI - Management of Behcet's syndrome. AB - PURPOSE OF REVIEW: Current trends in the management of Behcet's syndrome will be reviewed in this article. RECENT FINDINGS: Biologic agents have gained increasing importance over the years in the management of Behcet's syndrome. Long-term results of observational studies have shown that anti-tumor necrosis factor agents may be effective in Behcet's syndrome patients with refractory eye involvement. Case series reporting about use of anti-tumor necrosis factor agents in vascular and gastrointestinal involvement have also shown good results. Caution is required for infectious complications with these agents. Apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition. A randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated. SUMMARY: The outcome of Behcet's syndrome with major organ involvement has improved with more effective management strategies, especially with the use of biologic agents in severe cases. Controlled trials are needed to guide physicians in making treatment decisions. PMID- 26555451 TI - Bone remodeling in psoriasis and psoriatic arthritis: an update. AB - PURPOSE OF REVIEW: This article reviews and outlines recent advances in the field of bone remodeling in psoriatic disease and identify avenues for further research. RECENT FINDINGS: High-resolution imaging revealed that new bone formation, observed in psoriatic arthritis (PsA) is centered at enthesial sites in contrast to hand osteoarthritis, and new bone formation is also present in psoriasis patients without arthritis. Accumulating evidence strongly suggests that the IL-23/IL-17 pathway is directly involved in altered bone phenotypes in PsA. Apart from Th17 and Th22 cells, CD8IL-17 T cells, gammadeltaT cells, and type 3 innate lymphoid cells also secrete IL-17 and IL-22. Further studies will be needed to clarify the role of these cells in bone remodeling in the context of psoriatic disease. Recent research also strengthened the earlier viewpoint that mechanical stress can serve as a trigger for joint inflammation and arthritis development. Recent findings suggest that inflammation beginning in the skin may become more generalized and involve musculoskeletal structures. Other reports suggest that gut microbiota might have a role in joint inflammatory responses and bone remodeling in psoriatic disease. Successful application of omics approaches and advance imaging studies also revealed many novel aspects of psoriatic diseases and joint-related pathologies which will likely help pinpoint causal genes, pathways, and novel biomarkers in the near future. SUMMARY: Imaging studies have provided new insights into new bone formation phenotypes in PsA. The IL-23/IL-17 pathway is of central importance in psoriatic bone remodeling where, apart from CD4 T helper cells, other IL-17 and IL-22-secreting innate and adaptive cells may also be involved. Insights from study of the microbiome and from omics technologies will set the stage for new advances in our understanding of bone disorders in psoriatic diseases. PMID- 26555452 TI - Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data. AB - PURPOSE OF REVIEW: The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. RECENT FINDINGS: Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. SUMMARY: Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement. PMID- 26555453 TI - Vasculitis: a brief update. PMID- 26555454 TI - Mass Spectrometry in Precision Medicine: Phenotypic Measurements Alongside Pharmacogenomics. AB - BACKGROUND: Precision medicine is becoming a major topic within the medical community and is gaining traction as a standard approach in many disciplines. This approach typically revolves around the use of a patient's genetic makeup to allow the physician to choose the appropriate course of treatment. In many cases the genetic information directs the drug to be used to treat the patient. In other cases the genetic markers associated with enzyme function may inform dosage recommendations. However there is a second way in which precision medicine can be practiced-that is, by therapeutic drug monitoring (TDM). CONTENT: A review of the use of mass spectrometry for TDM in the arena of precision medicine is undertaken. Because the measurement of a drug or its metabolites provides the physician with a snapshot of the therapeutic exposure the patient is undergoing, these concentrations can be thought of as an actual phenotype measurement based around the patient's genetics coupled with all of the environmental, pharmacological, and nutritional variables. The outcome of a TDM measurement by mass spectrometry provides the patient's current phenotype vs the potential phenotype imputed by the genetics. SUMMARY: The use of mass spectrometry can provide an understanding of how a drug is interacting with the patient, and is orthoganol to the information provided by pharmacogenomic assays. Further, the speed and relatively low expense of drug monitoring by mass spectrometry makes it an ideal test for precision medicine patient management. PMID- 26555457 TI - Serial Hunt for Ciliary Genes in Complex Syndromes. PMID- 26555455 TI - Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation. AB - BACKGROUND: There is a clinical need for new technologies that would enable rapid disease diagnosis based on diagnostic molecular signatures. Ambient ionization mass spectrometry has revolutionized the means by which molecular information can be obtained from tissue samples in real time and with minimal sample pretreatment. New developments in ambient ionization techniques applied to clinical research suggest that ambient ionization mass spectrometry will soon become a routine medical tool for tissue diagnosis. CONTENT: This review summarizes the main developments in ambient ionization techniques applied to tissue analysis, with focus on desorption electrospray ionization mass spectrometry, probe electrospray ionization, touch spray, and rapid evaporative ionization mass spectrometry. We describe their applications to human cancer research and surgical margin evaluation, highlighting integrated approaches tested for ex vivo and in vivo human cancer tissue analysis. We also discuss the challenges for clinical implementation of these tools and offer perspectives on the future of the field. SUMMARY: A variety of studies have showcased the value of ambient ionization mass spectrometry for rapid and accurate cancer diagnosis. Small molecules have been identified as potential diagnostic biomarkers, including metabolites, fatty acids, and glycerophospholipids. Statistical analysis allows tissue discrimination with high accuracy rates (>95%) being common. This young field has challenges to overcome before it is ready to be broadly accepted as a medical tool for cancer diagnosis. Growing research in new, integrated ambient ionization mass spectrometry technologies and the ongoing improvements in the existing tools make this field very promising for future translation into the clinic. PMID- 26555458 TI - In Vitro Permeation of Metals through Human Skin: A Review and Recommendations. AB - During the last few decades, the interest in skin permeation of, specifically, metals has increased with the in vitro method utilizing diffusion cells as the prominent method of investigating permeability. This review provides a systematic synopsis focused on an in vitro diffusion cell method utilizing human skin and examines the differences in experimental design as this could influence the results obtained. The permeation of metals such as chromium, cobalt, copper, gold, lead, mercury, nickel, palladium, platinum, rhodium, silver, titanium, and zinc are discussed. The metals included in this review, except for titanium and zinc, can permeate through intact human skin under physiological conditions. On the basis of flux values, the order of permeability could be summarized as Cu > Pb > Cr > Ni > Co > Pt > Hg > Rh (excluding nanoparticles). Permeability of metals through human skin is highly variable with the different methodologies as a contributing factor. Furthermore, metals are retained in the skin which could lead to reservoir (depot) formation and extended exposure even after the removal thereof from the outer surface of the skin. Finally, recommendations are provided on the standardization of experimental design and format of data reporting to enable the comparison of results from future in vitro metal permeation studies. PMID- 26555456 TI - Endogenous ligands of the aryl hydrocarbon receptor regulate lung dendritic cell function. AB - The aryl hydrocarbon receptor (AhR) is a transcription factor that has been extensively studied as a regulator of toxicant metabolism. However, recent evidence indicates that the AhR also plays an important role in immunity. We hypothesized that the AhR is a novel, immune regulator of T helper type 2 (Th2) mediated allergic airway disease. Here, we report that AhR-deficient mice develop increased allergic responses to the model allergen ovalbumin (OVA), which are driven in part by increased dendritic cell (DC) functional activation. AhR knockout (AhR(-/-) ) mice sensitized and challenged with OVA develop an increased inflammatory response in the lung compared with wild-type controls, with greater numbers of inflammatory eosinophils and neutrophils, greater T-cell proliferation, greater production of Th2 cytokines, and higher levels of OVA specific IgE and IgG1. Lung DCs from AhR(-/-) mice stimulated antigen-specific proliferation and Th2 cytokine production by naive T cells in vitro. Additionally, AhR(-/-) DCs produced higher levels of tumour necrosis factor-alpha and interleukin-6, which promote Th2 differentiation, and expressed higher cell surface levels of stimulatory MHC Class II and CD86 molecules. Overall, loss of the AhR was associated with enhanced T-cell activation by pulmonary DCs and heightened pro-inflammatory allergic responses. This suggests that endogenous AhR ligands are involved in the normal regulation of Th2-mediated immunity in the lung via a DC-dependent mechanism. Therefore, the AhR may represent an important target for therapeutic intervention in allergic airways inflammation. PMID- 26555459 TI - Two highly adhesive lactic acid bacteria strains are protective in zebrafish infected with Aeromonas hydrophila by evocation of gut mucosal immunity. AB - AIMS: To increase the knowledge of probiotic effects and potential mechanisms, we report on the use of the zebrafish model to investigate the in vivo colonization ability, as well as the protective effects associated with gut mucosal immune barrier and responses against Aeromonas hydrophila infection of previously characterized probiotic lactic acid bacteria (LAB) strains, Bacillus coagulans 09.712 and Lactobacillus plantarum 08.923, in comparison with that of three commercialized strains. METHODS AND RESULTS: The results indicated differential adhesion capabilities, and B. coagulans and Lact. plantarum strains exhibited a more robust adhesion capability based on fluorescence observation. Oral delivery of these two strains in zebrafish greatly improved gut epithelium integrity, as well as reduced recruitment and degranulation of mast cells under Aer. hydrophila challenge. The percentage of intraepithelial lymphocytes (IELs) in probiotic fed groups was significantly higher than those in the control after challenge (P < 0.001). We also found that the abundance of IL-1beta mRNA in B. coagulans- and Lact. plantarum-fed groups remarkably decreased as a function of time of post challenge, and that of TNF-alpha and IL-10 mRNA was high with the probiotic treatment. CONCLUSIONS: Our findings indicate highly adhesive strains of B. coagulans 09.712 and Lact. plantarum 08.923 have immunoregulatory and immunoprotective roles in effective stimulation of anti-inflammatory response and barrier regeneration within the mucosa to protect zebrafish against infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work will further support zebrafish as a powerful model to better understand molecular definition of probiotic effects, as well as the probiotic potential of B. coagulans 09.712 and Lact. plantarum 08.923 of interest to the food industry. PMID- 26555460 TI - Gemcitabine-based chemotherapy in sarcomas: A systematic review of published trials. AB - Gemcitabine is largely used in the management of sarcomas. We have systematically reviewed all of the fully published trials that investigated a gemcitabine-based regimen in the management of sarcomas and then provided a grade of recommendations and a level of evidence for every recommendation. Because of conflicting results from successive non-randomized phase II trials, gemcitabine activity alone in unselected pretreated soft tissue sarcomas could not be properly assessed. Gemcitabine alone and gemcitabine-docetaxel appeared to both be active in pretreated uterine and non-uterine leiomyosarcoma (1B;I). Gemcitabine-dacarbazine appeared to be active in pretreated unselected soft tissue sarcomas (1B;I). According the GeDDIS phase III trial (not yet fully published), gemcitabine-docetaxel appeared slightly less active than doxorubicine and more toxic than doxorubicine in chemo-naive metastatic soft tissue sarcoma patients. Because of the absence of controlled randomized trials, the benefit of gemcitabine-docetaxel as an adjuvant treatment in high-grade uterine leiomyosarcoma could not be appropriately assessed. The level of activity of gemcitabine/docetaxel in bone sarcomas cannot be ascertained with the available data. The level of evidence supporting the use of gemcitabine-based regimens in sarcoma management is limited. Confirmatory phase III trials are warranted when phase II trials suggest some preliminary activity. PMID- 26555461 TI - Bevacizumab in ovarian cancer: Focus on clinical data and future perspectives. AB - The past five years have yielded substantial developments in the management of advanced ovarian cancer. Initial promise shown by anti-angiogenic agents has translated into positive phase III trials in the front-line and recurrent settings. Nevertheless, several questions remain unanswered, including the most appropriate timing for initiation of anti-angiogenic therapy and patient selection for the various treatment approaches. This review article summarises the key results (including final overall survival data), from five pivotal phase III trials of bevacizumab, highlights emerging data with new maintenance strategies and considers unanswered questions and ongoing research to address uncertainties in treatment duration, re-exposure to bevacizumab in bevacizumab pretreated patients and the potential integration of anti-angiogenic therapy into neoadjuvant treatment regimens. PMID- 26555462 TI - Eugene Minkowski (1885-1972): The Phenomenological Approach to Schizophrenia. PMID- 26555463 TI - Hyaluronic Acid--an "Old" Molecule with "New" Functions: Biosynthesis and Depolymerization of Hyaluronic Acid in Bacteria and Vertebrate Tissues Including during Carcinogenesis. AB - Hyaluronic acid is an evolutionarily ancient molecule commonly found in vertebrate tissues and capsules of some bacteria. Here we review modern data regarding structure, properties, and biological functions of hyaluronic acid in mammals and Streptococcus spp. bacteria. Various aspects of biogenesis and degradation of hyaluronic acid are discussed, biosynthesis and degradation metabolic pathways for glycosaminoglycan together with involved enzymes are described, and vertebrate and bacterial hyaluronan synthase genes are characterized. Special attention is given to the mechanisms underlying the biological action of hyaluronic acid as well as the interaction between polysaccharide and various proteins. In addition, all known signaling pathways involving hyaluronic acid are outlined. Impaired hyaluronic acid metabolism, changes in biopolymer molecular weight, hyaluronidase activity, and enzyme isoforms often accompany carcinogenesis. The interaction between cells and hyaluronic acid from extracellular matrix that may be important during malignant change is discussed. An expected role for high molecular weight hyaluronic acid in resistance of naked mole rat to oncologic diseases and the protective role of hyaluronic acid in bacteria are discussed. PMID- 26555464 TI - Chitin and Products of Its Hydrolysis in Vibrio cholerae Ecology. AB - The role of chitin and its hydrolysis products generated by Vibrio cholerae chitinases in mechanisms of its adaptation in water environments, metabolism, preservation, acquisition of pathogenic potential, and its epidemiological value are reviewed. Chitin utilization by V. cholerae as a source of energy, carbon, and nitrogen is described. Chitin association promotes biofilm formation on natural chitinous surfaces, increasing V. cholerae resistance to adverse factors in ecological niches: the human body and water environments with its inhabitants. Hydrolytic enzymes regulated by the corresponding genes result in complete chitin biodegradation by a chitinolytic catabolic cascade. Consequences of V. cholerae cell and chitin interaction at different hierarchical levels include metabolic and physiological cell reactions such as chemotaxis, cell division, biofilm formation, induction of genetic competence, and commensalic and symbiotic mutual relations with higher organisms, nutrient cycle, pathogenicity for humans, and water organisms that is an example of successful interrelation of bacteria and substratum in the ecology of the microorganism. PMID- 26555465 TI - Circulating microRNAs. AB - The detection of miRNAs in plasma and other body fluids opened up a fascinating possibility that animal noncoding RNAs can act as extracellular signaling molecules. In this review, we discuss recent progress in the field including the ability of miRNAs to participate in intercellular communication in vitro and in vivo, and the application of circulating miRNAs as diagnostic markers of a wide range of diseases. Special attention is paid to the relevance of the development and unification of current techniques for isolation of circulating miRNAs. PMID- 26555466 TI - Amyloids: from Pathogenesis to Function. AB - The term "amyloids" refers to fibrillar protein aggregates with cross-beta structure. They have been a subject of intense scrutiny since the middle of the previous century. First, this interest is due to association of amyloids with dozens of incurable human diseases called amyloidoses, which affect hundreds of millions of people. However, during the last decade the paradigm of amyloids as pathogens has changed due to an increase in understanding of their role as a specific variant of quaternary protein structure essential for the living cell. Thus, functional amyloids are found in all domains of the living world, and they fulfill a variety of roles ranging from biofilm formation in bacteria to long term memory regulation in higher eukaryotes. Prions, which are proteins capable of existing under the same conditions in two or more conformations at least one of which having infective properties, also typically have amyloid features. There are weighty reasons to believe that the currently known amyloids are only a minority of their real number. This review provides a retrospective analysis of stages in the development of amyloid biology that during the last decade resulted, on one hand, in reinterpretation of the biological role of amyloids, and on the other hand, in the development of systems biology of amyloids, or amyloidomics. PMID- 26555467 TI - Adaptive Epibiochemistry and Epigenetics. AB - Enzymatic reactions of post-synthetic modification of macromolecules occur in the cells of all organisms. These reactions, which can be designated as epibiochemical, are of a special type and, as discriminated from reactions with low molecular weight substrates, occur on the level of biopolymers, causing their covalent modification. The majority of epibiochemical modifications of proteins, DNA, and RNA are reversible and are carried out by modification transferases and de-modification enzymes, respectively. Epibiochemical, i.e. those located above the low molecular weight metabolites, modifications of proteins and nucleic acids perform various functions, including participation in molecular mechanisms of adaptive epigenetic heredity. This paper presents an overview of some adaptive epibiochemical modifications of macromolecules and the adaptive epigenetic processes on their basis. The features of epigenetic inheritance of acquired characteristics and the limits of biological evolution are discussed. PMID- 26555468 TI - Activity of Redox Enzymes in the Thallus of Anthoceros natalensis. AB - Anthocerotophyta (hornworts) belong to a group of ancient nonvascular plants and originate from a common ancestor with contemporary vascular plants. Hornworts represent a unique model for investigating mechanisms of formation of stress resistance in higher plants due to their high tolerance to the action of adverse environmental factors. In this work, we demonstrate that the thallus of Anthoceros natalensis exhibits high redox activity changing under stress. Dehydration of the thallus is accompanied by the decrease in activities of intracellular peroxidases, DOPA-peroxidases, and tyrosinases, while catalase activity increases. Subsequent rehydration results in the increase in peroxidase and catalase activities. Kinetic features of peroxidases and tyrosinases were characterized as well as the peroxidase isoenzyme composition of different fractions of the hornwort cell wall proteins. It was shown that the hornwort peroxidases are functionally similar to peroxidases of higher vascular plants including their ability to form superoxide anion-radical. The biochemical mechanism was elucidated, supporting the possible participation of peroxidases in the formation of reactive oxygen species (ROS) via substrate-substrate interactions in the hornwort thallus. It has been suggested that the ROS formation by peroxidases is an evolutionarily ancient process that emerged as a protective mechanism for enhancing adaptive responses of higher land plants and their adaptation to changing environmental conditions and successful colonization of various ecological niches. PMID- 26555469 TI - Peripheral Light-Harvesting LH2 Complex Can Be Assembled in Cells of Nonsulfur Purple Bacterium Rhodoblastus acidophilus without Carotenoids. AB - The effect of carotenoids on the assembly of LH2 complex in cells of the purple nonsulfur bacterium Rhodoblastus acidophilus was investigated. For this purpose, the bacterial culture was cultivated with an inhibitor of carotenoid biosynthesis - 71 uM diphenylamine (DPA). The inhibitor decreased the level of biosynthesis of the colored carotenoids in membranes by ~58%. It was found that a large amount of phytoene was accumulated in them. This carotenoid precursor was bound nonspecifically to LH2 complex and did not stabilize its structure. Thermostability testing of the isolated LH2 complex together with analysis of carotenoid composition revealed that the population of this complex was heterogeneous with respect to carotenoid composition. One fraction of the LH2 complex with carotenoid content around 90% remains stable and was not destroyed under heating for 15 min at 50 degrees C. The other fraction of LH2 complex containing on average less than one molecule of carotenoid per complex was destroyed under heating, forming a zone of free pigments (and polypeptides). The data suggest that a certain part of the LH2 complexes is assembled without carotenoids in cells of the nonsulfur bacterium Rbl. acidophilus grown with DPA. These data contradict the fact that the LH2 complex from nonsulfur bacteria cannot be assembled without carotenoids, but on the other hand, they are in good agreement with the results demonstrated in our earlier studies of the sulfur bacteria Allochromatium minutissimum and Ectothiorhodospira haloalkaliphila. Carotenoidless LH2 complex was obtained from these bacteria with the use of DPA (Moskalenko, A. A., and Makhneva, Z. K. (2012) J. Photochem. Photobiol., 108, 1 7; Ashikhmin, A., et al. (2014) Photosynth. Res., 119, 291-303). PMID- 26555470 TI - Low Concentrations of Hydrogen Peroxide Activate the Antioxidant Defense System in Human Sperm Cells. AB - The effect of low concentrations of hydrogen peroxide (10-100 uM) on sperm motility and on the activity of the sperm enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDS) was investigated. Incubation of semen samples with 10 and 100 uM hydrogen peroxide increased the content of spermatozoa with progressive motility by 20 and 18%, respectively, and enhanced the activity of GAPDS in the sperm cells by 27 and 20% compared to a semen sample incubated without additions. It was also found that incubation with 10 uM hydrogen peroxide increased the content of reduced glutathione (GSH) in sperm cells by 50% on average compared to that in the control samples. It is supposed that low concentrations of hydrogen peroxide activate the pentose phosphate pathway, resulting in NADPH synthesis and the reduction of the oxidized glutathione by glutathione reductase yielding GSH. The formed GSH reduces the oxidized cysteine residues of the GAPDS active site, increasing the activity of the enzyme, which in turn enhances the content of sperm cells with progressive motility. Thus, the increase in motile spermatozoa in the presence of low concentrations of hydrogen peroxide can serve as an indicator of normal functioning of the antioxidant defense system in sperm cells. PMID- 26555471 TI - Four Components of the Conjugated Redox System in Organisms: Carbon, Nitrogen, Sulfur, Oxygen. AB - C1 compounds participate in various metabolic processes and regulations including DNA methylation. Formaldehyde (FA), a product of methyl group oxidation, is highly cytotoxic. In the cell, there are two pathways of its utilization: assimilation and oxidation. Formaldehyde displays cytotoxicity, and therefore its oxidation is considered as detoxification. The sensitivity to the threshold concentration of FA we regard as an indication of its major role in biosystem functioning. A model of a three-component conjugated redox system is proposed in which the methyl group oxidation pathway is an archaic and conservative donor of protons and electrons, the reduction of O2 serves as an acceptor, and the arginine amino group is used for production of both urea and nitric oxide (the donor and acceptor, respectively). The fourth component of the redox system is glutathione, which maintains redox balance. The three-level system of proton donors includes the oxidation of a methyl group (first level), the oxidation of acetate in mitochondria (second level), and glucose catabolism in the pentose phosphate pathway (third level). The whole redox system is united by the sulfhydryl groups of cysteines, glutathione, thioredoxin, and alpha-lipoic acid. The central regulatory role in this redox system belongs to glutathione-dependent formaldehyde dehydrogenase, which controls FA binding with tetrahydrofolic acid, arginine methylation, and denitrosation of sulfhydryl groups. The conjugated redox system was formed during evolution as a union of separate redox cycles of carbon, nitrogen, sulfur, and oxygen. PMID- 26555472 TI - Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition. AB - BACKGROUND: Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size. METHODS AND RESULTS: ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP 1) and tumor necrosis factor (TNF-alpha). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-alpha, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-beta1 and oxLDL. CONCLUSIONS: Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions. PMID- 26555473 TI - Hydroxylated polycyclic aromatic hydrocarbons as biomarkers of exposure to wood smoke in wildland firefighters. AB - Wildland firefighter's exposure to wildland fire or vegetative biomass smoke has mostly been assessed by personal monitoring to airborne pollutants. However, the use of biomarkers may accurately reflect the internal (systemic) dose received by the firefighter. In this study, we assessed occupational exposure to wildland fire smoke in 14 wildland firefighters working at prescribed burns at the Savannah River Site, South Carolina by measuring the urinary concentrations of nine hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs). Except for 1-hydroxynaphthalene, preshift median concentrations of the OH-PAHs were higher compared with the median concentrations reported among the US general population, indicating elevated exposures to PAHs among the wildland firefighters during the prescribed burn season. The postshift concentrations of OH-PAHs were 83-323% (P<0.0001) higher compared with the preshift concentrations. Higher postshift concentrations of individual OH-PAHs were observed in 49 (87.5%) to 53 (94.6%) of all the 56 pre-post sample pairs. Additionally, the cross-shift (pre- to postshift) increase in 4-hydroxy-phenanthrene urinary concentration was marginally associated (P<0.1) with work shift exposure to PM2.5 and significantly associated (P<0.05) with levoglucosan, which is a marker of wildland fire or vegetative biomass smoke. These results suggest that OH-PAHs, especially 4PHE, may be useful biomarkers of wildland fire smoke exposure. PMID- 26555474 TI - Non-invasive saliva human biomonitoring: development of an in vitro platform. AB - Direct measurements of exposure represent the most accurate assessment of a subject's true exposure. The clearance of many drugs and chemicals, including pesticides such as chlorpyrifos (CPF), can be detected non-invasively in saliva. Here we have developed a serous-acinar transwell model system as an in vitro screening platform to prioritize chemicals for non-invasive biomonitoring through salivary clearance mechanisms. Rat primary serous-acinar cells express both alpha amylase and aquaporin-5 proteins and develop significant tight junctions at postconfluence - a feature necessary for chemical transport studies in vitro. CPF exhibited bidirectional passage across the serous-acinar barrier that was disproportional to the passage of a cell impermeable chemical (lucifer yellow), consistent with a hypothesized passive diffusion process. CPF was metabolized to trichlorpyridinol (TCPy) by serous-acinar cells, and TCPy also displayed bidirectional diffusion in the transwell assay. This model system should prove useful as an in vitro screening platform to support the non-invasive monitoring of toxicons and pharmacons in human saliva and provide guidance for development of advanced in vitro screening platforms utilizing primary human salivary gland epithelial cells. PMID- 26555475 TI - Efficacy of interventions targeting household air pollution from residential wood stoves. AB - Wood is commonly used for residential heating, but there are limited evidence based interventions for reducing wood smoke exposures in the indoor environment. The Asthma Randomized Trial of Indoor Wood Smoke (ARTIS) study was designed to assess the efficacy of residential interventions to reduce indoor PM exposure from wood stoves. As part of a three-arm randomized placebo-controlled trial, two household-level interventions were evaluated: wood stove changeouts and air filtration units. Exposure outcomes included indoor measures such as continuous PM2.5, particle counts, and carbon monoxide. Median indoor PM2.5 concentration was 17.5 MUg/m3 in wood-burning homes prior to interventions. No significant reductions in PM2.5 concentrations were observed in the 40 homes receiving the placebo filter intervention. Sixteen homes received the wood stove changeout and showed no significant changes in PM2.5 or particle counts. PM2.5 concentrations were reduced by 68% in the filter intervention homes. Relative to placebo, air filtration unit homes had an overall PM2.5 reduction of 63% (95% CI: 47-75%). Relative to the wood stove changeout, the filtration unit intervention was more efficacious and less expensive, yet compliance issues indicated a need for the evaluation of additional strategies for improving indoor air quality in homes using wood stoves. PMID- 26555478 TI - Factors influencing postpartum women's willingness to participate in a preventive pelvic floor muscle training program: a web-based survey. AB - OBJECTIVE: Pregnancy and delivery are the most prominent risk factors for the onset of pelvic floor injuries and - later-on - urinary incontinence. Supervised pelvic floor muscle training during and after pregnancy is proven effective for the prevention of urinary incontinence on the short term. However, only a minority of women do participate in preventive pelvic floor muscle training programs. Our aim was to analyze willingness to participate (WTP) in an intensive preventive pelvic floor muscle training (PFMT) program and influencing factors, from the perspective of postpartum women, for participation. STUDY DESIGN: We included 169 three-month postpartum women in a web-based survey in the Netherlands. Demographic and clinical characteristics, knowledge and experience with PFMT and preconditions for actual WTP were assessed. Main outcome measures were frequencies and percentages for categorical data. Cross tabulations were used to explore the relationship between WTP and various independent categorical variables. A linear regression analysis was done to analyze which variables are associated with WTP. RESULTS: A response rate of 64% (n=169) was achieved. 31% of the women was WTP, 41% was hesitating, 12% already participated in PFMT and 15% was not interested (at all). No statistically significant association was found between WTP and risk or prognostic pelvic floor dysfunction factors. Women already having symptoms of pelvic floor dysfunction such as incontinence and pelvic organ prolapse symptoms were more WTP (p=0.010, p=0.001, respectively) as were women perceiving better general health (p<0.001). Preconditions for women to participate were program costs, and travel time not exceeding 15min. CONCLUSIONS: From the perspective of postpartum women, there is room for improvement of preventive pelvic floor management. Further research should focus on strategies to tackle major barriers and to introduce facilitators for postpartum women to participate in PFMT programs. PMID- 26555476 TI - Interleukin-12 (IL-12)/STAT4 Axis Is an Important Element for beta-Cell Dysfunction Induced by Inflammatory Cytokines. AB - Pathology driving beta-cell loss in diabetes is poorly defined. Chronic subclinical inflammation is associated with beta-cell dysfunction. Acute in vitro exposure of islets and beta-cells to an inflammatory cytokine cocktail (IL 1beta/TNF-alpha/IFN-gamma) results in loss of cell function and viability. The contribution of each cytokine alone or in combination has been evaluated in homogeneous mouse beta-cell lines and primary mouse islets. Cytokine cooperation is required for beta-cell apoptosis with the most potent combinations including IL-1beta. Single cytokine exposure did not induce beta-cell apoptosis. Expression of endogenous interleukin-12 in beta-cells correlated with inflammatory cytokine combinations that induced beta-cell apoptosis. Uncoupling of the IL-12 axis by a block of IL-12 production, inhibition of IL-12 receptor/ligand interaction or disruption of IL-12 receptor signaling conferred protection to beta-cells from apoptosis induced by inflammatory cytokine stimulation. Signaling through STAT4 is indicated since disruption of IL-12 concomitantly reduced inflammatory cytokine stimulation of endogenous IFN-gamma expression. Primary mouse islets isolated from mice deficient in STAT4 show resistance to inflammatory-cytokine induced cell death when compared to islets isolated from wild type mice. Collectively, the data identify IL-12 as an important mediator of inflammation induced beta-cell apoptosis. Modulation of IL-12/STAT4 signaling may be a valuable therapeutic strategy to preserve islet/beta-cell viability in established diabetes. PMID- 26555480 TI - G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease. AB - Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4-40.5 pg/mL vs. 24.6 pg/mL IQR 16.4-34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents. PMID- 26555481 TI - [Chronic cervical vagal stimulation. Mechanisms of action and clinical relevance for heart failure]. AB - Increased sympathetic nerve activity and reduced vagal activity are associated with increased mortality in patients after myocardial infarction and patients with chronic heart failure; furthermore, vagal withdrawal has been documented to precede acute decompensation. Experimental studies have indicated that increased parasympathetic activity by means of vagal stimulation may reduce mortality in animal models of postinfarction sudden cardiac death and of chronic heart failure. First clinical results have demonstrated that chronic vagus nerve stimulation in heart failure patients with severe systolic dysfunction appears to be safe and tolerable and may improve the quality of life and left ventricular (LV) function. Vagus nerve stimulation gives rise to these potential clinical benefits by multiple mechanisms of action, including reduced heart rate, restoration of heart rate variability and baroreflex sensitivity, suppression of proinflammatory cytokines and antiarrhythmic effects. First clinical results suggest that vagal nerve stimulation is safe and tolerable and could lead to a marked clinical improvement but discrepancies in the findings due to different study designs warrant further discussion. PMID- 26555482 TI - Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats. AB - In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats. PMID- 26555483 TI - Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile. AB - Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products. PMID- 26555484 TI - A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis. AB - The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of cancer metastasis are still unclear. Animal models are essential for elucidating the mechanisms and for evaluating novel strategies for the treatment of metastatic cancers. Here, an in-depth description of a "patient-like" orthotopic syngeneic mouse model for exploring the mechanisms of metastasis of solid organ tumors is provided. The survival surgical implantation of BNL 1ME A.7R.1 mouse hepatocellular carcinoma cells directly into the liver (the organ of origin) of the inbred wild-type immune competent laboratory mouse strain, BALB/c is described. The success and reproducibility of this methodology recommends it for widespread use in elucidating the biological mechanisms of solid organ cancer metastasis. PMID- 26555485 TI - Gender differences in cognitive deficits in schizophrenia with and without diabetes. AB - This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40-68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes. However, diabetes exemplified the gender differences, especially in attention. PMID- 26555486 TI - Psychiatric disorders in patients with multiple sclerosis. AB - The aim of this study was to evaluate the frequency of psychiatric disorders, particularly mood disorders and anxiety in an outpatient sample of patients with multiple sclerosis in Brazil, and correlate the result with sociodemographic and clinical data. METHODS: Cross-sectional study, patients evaluated consecutively, for the clinical, demographic, prevalence of psychiatric disorders was used structured interview (MINI), severity of symptoms of depression and anxiety was used Beck inventory. RESULTS: The prevalence of major lifelong depression in this population was 36.6%, and the risk of suicide was high. There was no detectable correlation between depression, degree of disability, or disease duration. CONCLUSION: The prevalence of mood disorders is high in MS. Depression is an important factor related to the risk of suicide and should be investigated systematically. PMID- 26555487 TI - Onset polarity and illness course in bipolar I and II disorders: The predictive role of broadly defined mixed states. AB - Several studies investigating bipolar disorders have shown that polarity of onset can predict differences in symptomatology, course, and prognosis. Frequently, however, research on the topic has examined only bipolar I inpatients and has not included patients with mixed onset. The aim of the present naturalistic study was to evaluate the clinical characteristics and illness course of a consecutive sample (407 outpatients, 58.7% with bipolar I (BD-I) and 41.3% with bipolar II (BD-II) disorder) according to polarity of onset: depressive (DP-o); manic/hypomanic (HM-o); or mixed--broadly defined to include agitated depression for BD-II--onset (MX-o). As compared with patients in the other two groups: a) DP o patients (67.3%) were more frequently affected by BD-II and had lower ratings for psychotic symptoms; b) HM-o patients (17%) had a higher rate of family history for psychosis and a lower rate of suicide attempts; and c) patients in the MX-o group (15.7%) more frequently showed substance abuse and had a higher number of mixed recurrences per year. In the BD-II group, MX-o patients more frequently attempted suicide. The present study's main limitations are those of retrospective assessment of onset polarity and lack of treatment-impact evaluations over illness course. In conclusion, we confirm clinical expression differences in bipolar disorder in function of polarity of onset and underscore the importance of carefully considering broadly defined mixed state when examining polarity of onset. Further investigations are required to confirm the present study's results. PMID- 26555488 TI - The physician's quality of life: Relationship with ego defense mechanisms and object relations. AB - OBJECTIVE: To assess whether ego defense mechanisms and object relations (the way an individual subjectively experiences his/her relationships with others) are related to quality of life among physicians. METHODS: In this cross-sectional mail survey, 602 physicians from Botucatu, SP, Brazil, were sent a socio demographic questionnaire, the Bell Object Relations and Reality Testing Inventory-Form O (BORRTI-O), the Defense Style Questionnaire-40 (DSQ-40), and the World Health Organization Abbreviated Instrument for Quality of Life Assessment (WHOQOL-BREF). RESULTS: 198 questionnaires (33%) with valid responses were obtained. High BORRTI-O scores (indicative of pathology) on the alienation, egocentricity and insecure attachment subscales were associated with reduced WHOQOL-BREF scores for the psychological health and social relationship domains. Immature ego defense mechanisms were associated with lower WHOQOL-BREF scores for all domains. No significant associations of WHOQOL-BREF scores with working hours, workplace or monthly income were observed in the study population CONCLUSIONS: WHOQOL-BREF scores correlated with mature defense mechanisms and normal object relations, suggesting an association between psychological maturity and quality of life among physicians. PMID- 26555490 TI - Pathways from conflict-related trauma and ongoing adversity to posttraumatic stress disorder symptoms amongst West Papuan refugees: The mediating role of anxiety and panic-like symptoms. AB - BACKGROUND: Although the relationship involving exposure to traumatic events (TEs), conditions of adversity, and posttraumatic stress disorder (PTSD) is well established in the refugee field, the psychological factors mediating the relevant pathways are not as clearly delineated. In the present path analysis, we examined a model in which anxiety and panic-like symptoms mediated the path between conflict-related TEs, ongoing adversity, and PTS symptoms amongst 230 refugees from West Papua. METHODS: Culturally adapted measures were applied to assess TE exposure, ongoing adversity, anxiety, panic-like, PTS, and depressive symptoms. RESULTS: Our model identified two pathways leading from conflict related exposure to PTS symptoms, one a direct path, the other mediated by a sequence of ongoing adversity, anxiety and panic-like symptoms. Older refugees from West Papua had higher levels of anxiety and panic-like symptoms than the younger adult generation born in PNG. CONCLUSIONS: Our findings suggest that a focus on reducing anxiety and panic together with addressing social deprivations and threats may improve anxiety and panic amongst refugees, ultimately improving outcomes for PTS symptoms. PMID- 26555489 TI - Defining clinical severity in adults with obsessive-compulsive disorder. AB - OBJECTIVE: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is the most commonly used instrument to assess the clinical severity of obsessive-compulsive symptoms. Treatment determinations are often based on Y-BOCS score thresholds. However, these benchmarks are not empirically based, which may result in non evidence based treatment decisions. Accordingly, the present study sought to derive empirically-based benchmarks for defining obsessive-compulsive symptom severity. METHOD: Nine hundred fifty-four adult patients with obsessive compulsive disorder (OCD), recruited through the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders, were evaluated by experienced clinicians using a structured clinical interview, the Y-BOCS, and the Clinical Global Impressions-Severity scale (CGI-Severity). RESULTS: Similar to results in treatment-seeking children with OCD, our findings demonstrated convergence between the Y-BOCS and global OCD severity assessed by the CGI-Severity (Nagelkerke R(2)=.48). Y-BOCS scores of 0-13 corresponded with 'mild symptoms' (CGI-Severity=0-2), 14-25 with 'moderate symptoms' (CGI-Severity=3), 26-34 with 'moderate-severe symptoms' (CGI-Severity=4) and 35-40 with 'severe symptoms' (CGI Severity=5-6). Neither age nor ethnicity was associated with Y-BOCS scores, but females demonstrated more severe obsessive-compulsive symptoms than males (d=.34). Time spent on obsessions/compulsions, interference, distress, resistance, and control were significantly related to global OCD severity although the symptom resistance item pairing demonstrated a less robust relationship relative to other components of the Y-BOCS. CONCLUSIONS: These data provide empirically-based benchmarks on the Y-BOCS for defining the clinical severity of treatment seeking adults with OCD, which can be used for normative comparisons in the clinic and for future research. PMID- 26555491 TI - Posttraumatic stress symptoms and smoking among World Trade Center disaster responders: A longitudinal investigation. AB - PURPOSE: The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster. METHOD: Participants were 763 police and 1881 non-traditional (e.g., construction workers) WTC responders who reported being smokers at an initial examination obtained between July 2002 and July 2011 at the WTC Health Program (WTC-HP). WTC responders were reassessed, on average, 2.5 years later. RESULTS: For police WTC responders, higher levels of WTC-related PTSD symptoms at the initial visit were associated with a decreased likelihood of smoking abstinence (OR=0.98, p=.002) and with decreased smoking reduction (beta=-.06, p=.012) at the follow-up visit. WTC related PTSD symptom severity was not related to likelihood of smoking abstinence or change in number of cigarettes smoked among non-traditional responders. Post hoc analyses suggested that for police, hyperarousal PTSD symptoms were predictive of decreased abstinence likelihood at the follow-up visit (OR=0.56, p=.006). DISCUSSION: The present findings suggest that PTSD symptoms may be differentially related to smoking behavior among police and non-traditional WTC responders in a naturalistic, longitudinal investigation. Future work may benefit from exploring further which aspects of PTSD (as compared to each other and to common variance) explain smoking maintenance. PMID- 26555492 TI - Demoralisation syndrome does not explain the psychological profile of community based asylum-seekers. AB - BACKGROUND: Demoralisation syndrome (DS) has been advanced as a construct that features hopelessness, meaninglessness, and existential distress. Demoralisation and DS have predominantly been considered secondary only to illness; hence there is scant research on demoralisation or DS in populations affected by extreme environmental stress. AIMS: The current study aimed to determine the prevalence of demoralisation, its predictors, and the relevance of DS in a community-based forced-migrant population. METHOD: A convenience sample of 131 adult asylum seekers (n=98) and refugees (n=33) without recognised mental disorders in Melbourne, Australia, were assessed cross-sectionally on posttraumatic stress, anxiety, depression, post-migration stress, and demoralisation. Socio-demographic data were analysed with relevant clinical data. Predictive aims were investigated using bivariate statistical tests and exploratory aims were investigated using correlational and linear regression analyses. RESULTS: Seventy nine percent of the sample met criteria for demoralisation (asylum-seekers=83%; refugees=66%), with asylum-seekers being 2.55 (95% C.I.=1.03-6.32, Z=2.03, p=.04) times more likely to be demoralised than refugees. No relationship between demoralisation and time in the refugee determination process emerged. The regression model explained 47.5% of variance in demoralisation scores for the total sample F(9,111)=13.07, p<.0001, with MDD and anxiety score making unique significant contributions. CONCLUSIONS: Demoralisation was widespread through the asylum seeker and refugee population and its prevalence was attributable to a range of social and psychiatric factors. However, DS had little explanatory power for psychiatric morbidity, which was more suggestive of a pan-distress symptom complex. PMID- 26555493 TI - Awareness of treatment needs and length of stay amongst psychiatric inpatients. AB - INTRODUCTION: Inpatient psychiatric units experience significant pressure from third party payers to keep length of stay (LOS) to a minimum despite having to treat more severely ill patients. However, there is a paucity of empiric data for guiding treatment decisions that maximize therapeutic outcome while minimizing LOS. We therefore endeavored to begin utilizing a newly created psychometric instrument that assesses patient psychological factors, which we propose will allow for LOS prediction and individualization of therapeutic outcome. MATERIALS AND METHODS: The Goals Questionnaire (GQ), created to determine awareness of treatment needs, was administered to newly admitted patients. Linear regression analyses were conducted to ascertain the relationship between the GQ score and LOS, as well as the effects of confounding factors. RESULTS: A significant and inverse relationship was found between the GQ score and LOS (beta=-4.4; p=0.007) that was dependent upon (i.e., had a significant interaction with) age and substance use disorders. There was minimal confounding from common administrative, legal, and clinical factors. CONCLUSIONS: The GQ may have utility for inpatient treatment teams, providing information that can be used to maximize and individualize therapeutic outcome while minimizing LOS. PMID- 26555494 TI - Gray matter volume abnormalities were associated with sustained attention in unmedicated major depression. AB - BACKGROUND: Impaired sustained attention seems to be a core feature of depression while the anatomical alteration of brain was widely reported in depression patients. The authors aimed to identify the relationship between anatomical brain changes and sustained attention deficits in unmedicated patients with major depressive disorder (MDD). METHODS: A total of 51 medication-free MDD patients and 51 matched healthy controls (HC) underwent high-resolution structural magnetic resonance imaging scanning, and optimized voxel-based morphometry method was performed to analyze the changes of gray matter volume (GMV). We employed a computerized neurocognitive task from the Cambridge Neuropsychological Tests Automated Battery (CANTAB)--Rapid Visual Information Processing (RVP) task--as a measurement of sustained attention. Based on clinical symptoms, 40 patients who had completed CANTAB-RVP test were divided into MDDa (mild depression patients) and MDDb (severe depression patients) groups. Then the relationships among sustained attention, GMV of different regions and clinical symptoms were explored separately. RESULTS: MDD patients showed significant GMV increase in left posterior cingulate cortex (PCC) and inferior frontal gyrus (IFG) (p<0.001, uncorrected), and significant GMV decrease in medial/superior frontal gyrus (MFG/SFG) and lingual gyrus (p<0.001, uncorrected). Structure-cognition correlation analyses revealed that in MDD patients, GMV alterations of the IFG were significantly correlated with sustained attention as measured by the CANTAB RVP. CONCLUSIONS: Increased GMV values of IFG were associated with sustained attention which may underlie the pathophysiology of MDD or be part of the cognition circuit. In the severe depression patients, sustained attention deficits were positively correlated with clinical symptoms. PMID- 26555495 TI - Does the interpersonal model apply across eating disorder diagnostic groups? A structural equation modeling approach. AB - BACKGROUND: Interpersonal model has been validated with binge-eating disorder (BED), but it is not yet known if the model applies across a range of eating disorders (ED). PURPOSE: The goal of this study was to investigate the validity of the interpersonal model in anorexia nervosa (restricting type; ANR and binge eating/purge type; ANBP), bulimia nervosa (BN), BED, and eating disorder not otherwise specified (EDNOS). PROCEDURE: Data from a cross-sectional sample of 1459 treatment-seeking women diagnosed with ANR, ANBP, BN, BED and EDNOS were examined for indirect effects of interpersonal problems on ED psychopathology mediated through negative affect. RESULTS: Findings from structural equation modeling demonstrated the mediating role of negative affect in four of the five diagnostic groups. There were significant, medium to large (.239, .558), indirect effects in the ANR, BN, BED and EDNOS groups but not in the ANBP group. The results of the first reverse model of interpersonal problems as a mediator between negative affect and ED psychopathology were nonsignificant, suggesting the specificity of these hypothesized paths. However, in the second reverse model ED psychopathology was related to interpersonal problems indirectly through negative affect. CONCLUSION: This is the first study to find support for the interpersonal model of ED in a clinical sample of women with diverse ED diagnoses, though there may be a reciprocal relationship between ED psychopathology and relationship problems through negative affect. Negative affect partially explains the relationship between interpersonal problems and ED psychopathology in women diagnosed with ANR, BN, BED and EDNOS. Interpersonal psychotherapies for ED may be addressing the underlying interpersonal-affective difficulties, thereby reducing ED psychopathology. PMID- 26555496 TI - Illness perception in systemic lupus erythematosus patients: The roles of alexithymia and depression. AB - OBJECTIVE: Alexithymia and depressive mood have been described as important dimensions of several medical diseases. Systemic lupus erythematosus is a chronic condition characterized by unpredictable clinical manifestations. The relationships between alexithymia, depression, and illness perception were examined in systemic lupus erythematosus patients. The interrelationships between psychological factors, such as alexithymia and depressive mood, were explored in systemic lupus erythematosus patients, and associations between these factors and illness perception in SLE were examined. We hypothesized that alexithymia and negative perceptions of illness would be associated in SLE patients, and depression would mediate this relationship. METHODS: Subjects were 100 consecutive systemic lupus erythematosus patients attending the outpatient clinic at the University of Pisa rheumatology unit. They completed the Toronto Alexithymia Scale, Beck Depression Inventory, and Revised Illness Perceptions Questionnaire. Clinical variables were measured, disease activity was evaluated using the European Consensus Lupus Activity Measure, and damage was assessed using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index. RESULTS: There were no associations between clinical variables, alexithymia, and depression. The results highlight the existence of significant links between alexithymia and illness perception for systemic lupus erythematosus patients. Moreover, our data suggest that some of these links are mediated by depression, which is the direct predictor of different aspects of perceived health. CONCLUSION: Our findings suggest that studying the role of psychological factors, such as alexithymia and depression, may contribute to a more comprehensive perspective of systemic lupus erythematosus, including their impact on patients' beliefs about treatment effectiveness and emotional adaptation to chronic disease. PMID- 26555497 TI - Psychometric properties of the Haitian Creole version of the Resilience Scale with a sample of adult survivors of the 2010 earthquake. AB - BACKGROUND: Resilience is defined as the ability of people to cope with disasters and significant life adversities. The present paper aims to investigate the underlying structure of the Creole version of the Resilience Scale and its psychometric properties using a sample of adult survivors of the 2010 earthquake. METHODS: A parallel analysis was conducted to determine the number of factors to extract and confirmatory factor analysis was performed using a sample of 1355 adult survivors of the 2010 earthquake from people of specific places where earthquake occurred with an average age of 31.57 (SD=14.42). All participants completed the Creole version of Resilience Scale (RS), the Impact of Event Scale Revised (IES-R), the Beck Depression Inventory (BDI) and the Social Support Questionnaire (SQQ-6). To facilitate exploratory (EFA) and confirmatory factor analysis (CFA), the sample was divided into two subsamples (subsample 1 for EFA and subsample 2 for CFA). RESULTS: Parallel analysis and confirmatory factor analysis results showed a good-fit 3-factor structure. The Cronbach alpha coefficient was .79, .74 and .72 respectively for the factor 1, 2 and 3 and correlated to each other. Construct validity of the Resilience scale was provided by significant correlation with measures of depression and social support satisfaction, but no correlation was found with posttraumatic stress disorder measure, except for factor 2. CONCLUSIONS: The results reveal a different factorial structure including 25 items of the RS. However, the Haitian Creole version of RS is a valid and reliable measure for assessing resilience for adults in Haiti. PMID- 26555498 TI - The 6-item Kessler psychological distress scale to survey serious mental illness among Chinese undergraduates: Psychometric properties and prevalence estimate. AB - OBJECTIVE: To evaluate the psychometric properties of the 6-item Kessler psychological distress scale (K6) in screening for serious mental illness (SMI) among undergraduates in a major comprehensive university in China. METHOD: The K6 was self-completed by 8289 randomly sampled participants. A group of them (n=222) were re-assessed using K6 and interviewed using the Chinese version of Composite International Diagnostic Interview 3.1 (CIDI-3.1). RESULTS: The test-retest reliability of the K6 scale was 0.79, the Cronbach's alpha was 0.84, and its area under the receiver operating curve (AUC) for diagnosing CIDI-3.1 SMI was 0.85 (95% CI=0.80-0.90). For the optimal cut-off of K6 (12/13), the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and classification accuracy (AC) were 0.83, 0.79, 0.60, 0.93, and 0.80, respectively. The 12-month prevalence of SMI was estimated as 3.97% using this optimal cut-off. Binary logistic regression analysis (including gender, ethnicity, grade, number of siblings and family residency location) showed that only family residency location in rural areas compared to urban areas was significantly associated with more SMI. CONCLUSIONS: This study documented the value of using the K6 for detecting SMI in Chinese undergraduate populations and supported its cross-cultural reliability and validity. PMID- 26555499 TI - Racial disparities during admission to an academic psychiatric hospital in a large urban area. AB - Multiple studies confirm that African Americans are less likely than non-Hispanic whites to receive needed mental health services. Research has consistently shown that African Americans are under-represented in outpatient mental health treatment settings and are over-represented in inpatient psychiatric settings. Further, African Americans are more likely to receive a diagnosis of schizophrenia and are less likely receive an affective disorder diagnosis during inpatient psychiatric hospitalization compared to non-Hispanic white patients, pointing to a need for examining factors contributing to mental health disparities. Using Andersen's Behavioral Model of Health Service Use, this study examined predisposing, enabling and need factors differentially associated with health service utilization among African American and non-Hispanic white patients (n=5183) during psychiatric admission. We conducted univariate and multivariate logistic regression analyses to examine both main effects and interactions. In the multivariate model, African American race at admission was predicted by multiple factors including younger age, female gender, multiple psychiatric hospitalizations, elevated positive and negative symptoms of psychosis, a diagnosis of schizophrenia and substance use, as well as having housing and commercial insurance. Additionally, screening positive for cannabis use at intake was found to moderate the relationship between being female and African American. Our study findings highlight the importance of examining mental health disparities using a conceptual framework developed for vulnerable populations (such as racial minorities and patients with co-occurring substance use). PMID- 26555500 TI - The role of emotion regulation strategies and dissociation in non-suicidal self injury for women with borderline personality disorder and comorbid eating disorder. AB - Different dysfunctional emotion regulation strategies are observed in patients with borderline personality disorder (BPD) and comorbid eating disorders (EDs) who report non-suicidal self-injury (NSSI). The objective of this study was to investigate the relationship of two well-defined emotion regulation strategies (i.e. expressive suppression and cognitive reappraisal) and dissociation with NSSI. The participants were sixty-eight women diagnosed with BPD and comorbid ED. A cross-sectional research design was used, and clinical interviews and self report questionnaires were administered to collect data. Multiple regression was conducted to analyze the relationship of two emotion regulation strategies and dissociation with NSSI. According to the results, for low cognitive reappraisal scores, an increase in dissociation leads to an increase in NSSI; however, as cognitive reappraisal increases, higher dissociation is associated with fewer NSSI. When expressive suppression is low, an increase in cognitive reappraisal is associated with a decrease in NSSI; however, as suppression increases, a higher cognitive reappraisal has less effect on decreasing NSSI. These findings indicate that cognitive reappraisal reduces the harmful effects that dissociation has on NSSI, and that expressive suppression interferes with the beneficial effects of cognitive reappraisal on NSSI. Therefore, targeting expressive suppression before cognitive reappraisal is conducted may enhance treatment outcomes for patients with BPD and comorbid ED. PMID- 26555501 TI - Evaluation of the hip-flask defence by determination of ethyl glucuronide and ethyl sulphate concentrations in blood. AB - INTRODUCTION: The hip-flask defence (i.e. claiming ethanol intake after an incident) is difficult to refute by the use of ethanol analyses alone, as these may show decreasing concentrations shortly after intake of alcohol. The non oxidative metabolites of ethanol, ethyl glucuronide (EtG) and ethyl sulphate (EtS) have a different pharmacokinetic profile, with peak concentrations in blood around 4h after intake. The aim of this study was to describe a method for using EtG-analysis for the purpose of estimating the time point of ethanol intake and to report cases in which this method is used. METHODS: Previously published studies are summarised. Also, in expert witness cases where the hip-flask defence is claimed, EtG and EtS were analysed in selected cases. Twelve such cases are reported. RESULTS: In previous studies, about 70 healthy volunteers have been included in different kinetic studies, demonstrating maximal individual concentrations of EtG always below 0.5 mg/L after 1 h, below 1 mg/L after 2 h and somewhat above 1 mg/L 4 h after a moderate alcohol intake (up to 80 grams of ethanol). Twelve cases are reported in the present study, where the suspect claimed no alcohol intake before driving, only intake after driving. In all 12 cases, ethanol concentration was lower in the second sample (taken approximately 30 min after the first). The median EtG concentration in the first sample was 4.13 mg/L (range 2.0-7.4) and 4.34 mg/L (range 2.1-7.2) in the second sample. One case showed an increase in EtG concentrations of 15% from first to second sample (the time difference between the samples was 32 min, with the first sample taken 41 min after driving). For the remainder of the cases, EtG concentrations were relatively stable. CONCLUSIONS: In all the presented cases, the levels of EtG were substantially higher than what would be expected only about 1-2h after a very recent alcohol intake. The relatively stable concentrations between the first and second sample also indicated that the high EtG concentrations were not caused by a rapid formation after a recent intake, as this would have demonstrated increasing concentrations over a time period of 30 min. In conclusion, EtG and EtS in blood could be a helpful tool in assessment of the hip flask defence, in cases where the detected ethanol is claimed to be caused solely by a single intake after driving. PMID- 26555502 TI - A new method of artificial latent fingerprint creation using artificial sweat and inkjet printer. AB - In order to study fingerprinting in the field of forensic science, it is very important to have two or more latent fingerprints with identical chemical composition and intensity. However, it is impossible to obtain identical fingerprints, in reality, because fingerprinting comes out slightly differently every time. A previous research study had proposed an artificial fingerprint creation method in which inkjet ink was replaced with amino acids and sodium chloride solution: the components of human sweat. But, this method had some drawbacks: divalent cations were not added while formulating the artificial sweat solution, and diluted solutions were used for creating weakly deposited latent fingerprint. In this study, a method was developed for overcoming the drawbacks of the methods used in the previous study. Several divalent cations were added in this study because the amino acid-ninhydrin (or some of its analogues) complex is known to react with divalent cations to produce a photoluminescent product; and, similarly, the amino acid-1,2-indanedione complex is known to be catalyzed by a small amount of zinc ions to produce a highly photoluminescent product. Also, in this study, a new technique was developed which enables to adjust the intensity when printing the latent fingerprint patterns. In this method, image processing software is used to control the intensity of the master fingerprint patterns, which adjusts the printing intensity of the latent fingerprints. This new method opened the way to produce a more realistic artificial fingerprint in various strengths with one artificial sweat working solution. PMID- 26555504 TI - Risk and risk perception of knee osteoarthritis in the US: a population-based study. AB - OBJECTIVE: We sought to investigate risk perception among an online cohort of younger US adults compared with calculated risk estimates. DESIGN: We recruited a population-based cohort 25-44 years of age with no history of knee osteoarthritis (OA) using Amazon's Mechanical Turk, an online marketplace used extensively for behavioral research. After collecting demographic and risk factor information, we asked participants to estimate their 10-year and lifetime risk of knee OA. We compared perceived risk with risk derived from the OA risk calculator (OA Risk C), an online tool built on the basis of the validated OA Policy Model. RESULTS: 375 people completed the study. 21% reported having 3+ risk factors for OA, 25% reported two risk factors, and 32% reported one risk factor. Using the OA Risk C, we calculated a mean lifetime OA risk of 25% and 10-year risk of 4% for this sample. Participants overestimated their lifetime and 10-year OA risk at 48% and 26%, respectively. We found that obesity, female sex, family history of OA, history of knee injury, and occupational exposure were all significantly associated with greater perceived lifetime risk of OA. CONCLUSIONS: Risk factors are prevalent in this relatively young cohort. Participants consistently overestimated their lifetime risk and showed even greater overestimation of their 10-year risk, suggesting a lack of knowledge about the timing of OA onset. These data offer insights for awareness and risk interventions among younger persons at risk for knee OA. PMID- 26555503 TI - Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study. AB - Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD. PMID- 26555505 TI - The Relationship between Cultural Anxiety and Ethnic Essentialism: The Mediating Role of an Endorsement of Multicultural Ideology. AB - Many studies have explored the social consequences of ethnic essentialism in recent decades. In addition, a few studies have focused on the impact of perceived cultural context on ethnic essentialism. However, it is not clear why perceived cultural context can lead to changes in ethnic essentialism. In the present study, we hypothesized that the cultural anxiety of ethnic minorities may trigger a strong endorsement of and support for a multicultural ideology, thereby affecting beliefs about ethnic groups. To address the issue, 226 Tibetan and 102 Hui college students from Mainland China completed our questionnaires. The results across the two samples showed that (1) cultural anxiety was positively associated with both the endorsement of a multicultural ideology and ethnic essentialism, (2) cultural anxiety and the endorsement of a multicultural ideology positively predicted ethnic essentialism after controlling for demographic variables, and (3) cultural anxiety had both a direct effect on ethnic essentialism and an indirect effect on ethnic essentialism through the endorsement of a multicultural ideology. Our findings suggest that when ethnic minorities experience cultural anxiety, they might endorse a multicultural ideology and adopt essentialism to affirm their ethnic identities. PMID- 26555506 TI - Frontobasal Midline Meningiomas: Is It Right To Shed Doubt on the Transcranial Approaches? Updates and Review of the Literature. AB - BACKGROUND: Traditionally, the surgical removal of tuberculum sellae meningioma (TSM) and olfactory groove meningioma (OGM) requires transcranial approaches and microsurgical techniques, but in the last decade endoscopic expanded endonasal approaches have been introduced: transcribriform for OGMs and transtuberculum transplanum for TSM. A comparative analysis of the literature concerning the two types of surgical treatment of OGMs and TSM is, however, difficult. METHODS: We conducted a literature search using the PubMed database to compare data for endoscopic and microsurgical techniques in the literature. We also conducted a retrospective analysis of selected cases from our series presenting favorable characteristics for an endoscopic approach, based on the criteria of operability of these lesions as generally accepted in the literature, and we compared the results obtained in these patients with those in the endoscopic literature. RESULTS: We believe that making the sample more homogeneous, the difference between microsurgical technique and endoscopic technique is no longer so striking. A greater radical removal rate, a reduced incidence of cerebrospinal fluid fistula and, especially, the possibility of removing lesions of any size are advantages of transcranial surgery; a higher percentage of improvement in visual outcome and a lower risk of a worsening of a pre-existing deficit or onset of a new deficit are advantages of the endoscopic technique. CONCLUSION: At present, the microsurgical technique is still the gold standard for the removal of the anterior cranial fossa meningiomas of all sizes, and the endoscopic technique remains a second option in certain cases. PMID- 26555507 TI - How Does Brainstem Involvement Affect Prognosis in Patients with Limited Brain Metastases? Results of a Matched-Cohort Analysis. AB - OBJECTIVE: Although brainstem metastases are thought to portend an inferior prognosis compared to non-brainstem brain metastases, there is limited evidence to support this claim, particularly in the modern radiosurgical era. METHODS: We collected the clinical data for 500 patients with brain metastases treated at our institution with stereotactic radiosurgery (SRS). All patients received SRS to at least one brain metastasis, and all brainstem metastases underwent SRS. After propensity score matching, clinical characteristics and overall survival were calculated and compared between groups. RESULTS: Three hundred sixteen patients with brain metastases were analyzed after matching (143 with brainstem involvement and 173 without). Patients with brainstem metastases lived shorter after first SRS than patients without brainstem metastases did (median 4.4 and 6.5 months, respectively; P = 0.01), and they were more likely to have received whole brain irradiation (P = 0.003). Patients with a single metastasis did not survive longer than patients with multiple brain metastases if there was brainstem involvement (P = 0.45). The incidence of new extracranial disease and severe toxicity after SRS did not differ between groups. CONCLUSIONS: The survival of patients with brain metastases is inferior after a metastatic lesion develops within the brainstem, despite favorable local control with brainstem SRS. The brainstem location should be considered a negative prognostic factor for survival after SRS, and it could result from the eloquence of this location. Future research could identify the clinically life-limiting component of brainstem metastases. PMID- 26555508 TI - Historical Landmarks in the Management of Aneurysms and Arteriovenous Malformations of the Central Nervous System. AB - OBJECTIVE: To describe the history of vascular and endovascular neurosurgery. METHODS: A literature research was conducted including historical events from 2000 bc to the twenty-first century ad, and a timetable was filled with information regarding the most representative historical landmarks regarding vascular and endovascular neurosurgery. RESULTS: Starting from approaches limited to the cervical carotid artery, vascular neurosurgery gained its way through the intracranial and finally endovascular space thanks to the introduction of both innovative and progressively less invasive procedures. With the invention of cerebral angiography in 1927, Egas Moniz paved the way for modern endovascular neurosurgery. CONCLUSIONS: Numerous pioneers have been described through this historical reconstruction. Their genius, effort, dedication, and passion brought a massive contribution to vascular and endovascular neurosurgery as we know it today. PMID- 26555509 TI - Oxidative stress parameters and serum magnesium levels in patients with seasonal allergic conjunctivitis. AB - OBJECTIVE: To evaluate oxidative stress parameters and serum magnesium (Mg) levels in patients with seasonal allergic conjunctivitis (SAC) during the pollen season. METHODS: This observational cross-sectional study involved 35 patients with SAC without any other ocular and systemic diseases, and 38 consecutive, age- and sex-matched healthy subjects. Serum malondialdehyde (MDA), adjusted ischemia modified albumin (IMA), and Mg levels were quantified, and the results were compared between the groups. RESULTS: No significant differences were found between the groups with respect to age (p = 0.416) and sex (p = 0.362). Serum MDA and adjusted IMA levels of the subjects with SAC (69.54 +/- 7.71 MUM and 0.74 +/- 0.39 ABSU) were significantly higher than the control group (64.61 +/- 5.89 MUM and 0.57 +/- 0.19 ABSU) (p = 0.002 and p = 0.025, respectively). There was no significant difference for serum Mg levels between the groups (p = 0.177). CONCLUSION: We demonstrated higher levels of oxidative stress parameters in patients with SAC compared to the control group, which imply a possible role of oxidative stress in the pathogenesis of SAC. PMID- 26555510 TI - Variable protein profiles in extracellular products of the protistan parasite Perkinsus olseni among regions of the Spanish coast. AB - The variability of the protein expression profiling in the extracellular products (ECPs) of in vitro cultured Perkinsus olseni deriving from 4 regions of the Spanish coast was evaluated. The regions involved were the rias of Arousa and Pontevedra (Galicia, NW Spain), Carreras River (Andalusia, SW Spain) and Delta de l'Ebre (Catalonia, NE Spain). P. olseni in vitro clonal cultures were produced from parasite isolates from four clams from each region. Proteins released by the in vitro cultured parasites were isolated and separated by two dimensional electrophoresis (2DE). Qualitative comparison of protein expression profiles in the P. olseni ECPs among clones from all the regions was performed with PD Quest software. Around 130 spots were counted in the gels from ECPs of P. olseni clones from each region, of which 23 spots were shared by clones from all the regions and various spots were representative from clones of one region (appear in every clonal culture from that region but did not in every one of the other regions). A total of 34 spots were excised from the gels and analysed for sequencing. The protein cathepsin B, involved in proteolysis, the signal recognition particle receptor subunit beta, involved in protein transport through membranes, and a protein belonging to N-acetyl transferase superfamily, involved in biosynthesis, were identified in spots shared by P. olseni ECPs from all regions. Pepsin A precursor, involved in proteolysis; heat shock protein (HSP) 60; and phosphoserine aminotransferase, involved in biosynthesis, were representative of P. olseni ECPs from Ria de Arousa, while peroxiredoxin V, involved in oxidation reduction, was representative of P. olseni ECPs from Ria de Pontevedra. Differences in released proteins suggest different virulence or resistance to host attack between parasites from different locations. PMID- 26555511 TI - A need for orientation: The WMA statement on natural variations of human sexuality. AB - An alarming stigmatization and discrimination of homosexual people persists despite the formal depathologization of homosexuality, which occurred through the removal of the diagnosis from the DSM- (1973) and classification from the ICD (1991). The adoption of an expedited Statement on sexual orientation by the majority at the 64th General Assembly of the WMA is therefore an important and overdue measure. The Statement clearly asserts, among other things, that homosexuality is not an illness and therefore requires no cure. It also suggests that direct and indirect discrimination and stigmatization of people due their sexual orientation often leads to psychological and physical illnesses. Furthermore, delegates of the WMA condemned so-called reparative or conversion "therapies", which strive to induce heterosexual or asexual behavior. These are not only ineffective and unethical, but are strongly associated with serious negative impacts on health. Such a statement from the World Medical Association (WMA) is of particular importance as ambivalence and uncertainty in regards to homosexuality exists even within the medical and therapeutic professions. The latent or manifest attribution of homosexuality as an illness or developmental disorder is still widespread. One possible explanation for this may be the disruption of an open and sustainable discourse on causes, effects and definitions of sexual orientation following the "official depathologization". Especially those working in the medical and therapeutic contexts should be aware of their special responsibility not to pathologize homosexuality. PMID- 26555513 TI - Retraction. Evaluation of Selected Nutrients and Contaminants in Distillers Grains from Ethanol Production in Texas. PMID- 26555512 TI - A matter of sexual confidence: young men's non-prescription use of Viagra in Addis Ababa, Ethiopia. AB - This paper examines the non-prescription use of the sexual enhancement drug Viagra by young men in Addis Ababa. Data was collected through repeated in-depth interviews with 14 Viagra users - heterosexual men between the ages of 21 and 35 and focus-group discussions with 21 male and 22 female university students. Study participants turned to Viagra to impress lovers, as a 'support mechanism' when feeling weak or tired, to counteract the effects of chewing the stimulant plant khat and to satisfy what they perceived as a psychological 'addiction'. More generally, young men used Viagra to quell anxieties about what they perceived as women's growing expectations about their sexual performance - informed by changing gender relations and sexual expectations, constructions of masculinity that emphasise sexual prowess, and a misreading of women's sexual desires largely fuelled by the emergence of pornography as a new standard for sexual performance. While some men gained sexual confidence by using Viagra, others - particularly those who used Viagra regularly - paradoxically experienced feelings of loss of manhood. PMID- 26555514 TI - Incidence, Antimicrobial Resistance, and Molecular Characteristics of Nontyphoidal Salmonella Including Extended-Spectrum beta-Lactamase Producers in Retail Chicken Meat. AB - The present study was undertaken to determine the prevalence of Salmonella in 100 chicken carcass samples from five integrated broiler operation brands in Korea. Serotypes, antibiotic resistance patterns, extended-spectrum beta-lactamase (ESBL) genotype, and clonal divergence using multilocus sequence typing of the isolated strains were analyzed. A total of 42 chicken samples were contaminated with nontyphoidal Salmonella (NTS) isolates: 16 isolates (38%) were Salmonella Virchow, 9 (21%) were Salmonella Bareilly, and 8 (19%) were Salmonella Infantis. A multidrug resistance (MDR; resistant to more than three classes of antibiotics) phenotype was observed in 29% of the isolates, which were resistant to five or more classes of antibiotics. The dominant MDR type was resistance to classes of penicillin, cephalosporins, aminoglycosides, quinolones, and tetracyclines. All the MDR isolates were positive for ESBL producers, and all but one (with the CTX M-1 genotype) had the CTX-M-15 genotype. Multilocus sequence typing of the isolates revealed ST16 as the dominant sequence type; Salmonella Virchow, Salmonella Infantis, and Salmonella Richmond were all ST16, indicating a close genetic relationship between these serovars. This is the first study in Korea showing the CTX-M-1 type of NTS and the prevalence of ESBL-producing strains among NTS isolated from retail chicken meat. Our findings suggest that MDR Salmonella contamination is widely prevalent in retail chicken meat, and consumption of inadequately cooked products could lead to dissemination of NTS, which is hazardous to human health. PMID- 26555515 TI - Prevalence and Serogroup Diversity of Salmonella for Broiler Neck Skin, Whole Carcass Rinse, and Whole Carcass Enrichment Sampling Methodologies following Air or Immersion Chilling. AB - The purpose of this study was to evaluate neck skin (NS), whole carcass rinse (WCR), and whole carcass enrichment (WCE) sampling procedures for Salmonella isolation and serogroup identification from the same broiler chicken carcass treated with air or immersion chilling. Commercially processed and eviscerated broiler carcasses were collected from a commercial processing plant, individually bagged, and transported to the pilot processing plant. In experiment 1, carcasses were air chilled to 4 degrees C. In experiment 2, carcasses were immersion chilled with or without chlorine. After air chilling, Salmonella was detected on 78% of NS and 89% of WCE samples. Only one Salmonella serogroup was detected from each of 13 Salmonella-positive NS samples, and two serogroups were detected on 1 Salmonella-positive NS sample. Only one Salmonella serogroup was detected from each of 13 Salmonella-positive WCE samples, and two serogroups were detected from 3 Salmonella-positive WCE samples. After immersion chilling without chlorine, Salmonella was detected on 38% of NS, 45% of WCR, and 100% of WCE samples. Without chlorine, the 15 Salmonella-positive NS samples included 14 samples with one serogroup and 1 sample with two serogroups. Only one Salmonella serogroup was detected from WCR samples after immersion chilling. Of 40 Salmonella-positive WCE samples, 23 had a one, 14 had two, and 3 had three Salmonella serogroups. After immersion chilling with chlorine, Salmonella was detected on 35% of NS, 0% of WCR, and 90% of WCE samples. With chlorine, the 14 Salmonella-positive NS samples included 11 samples with one serogroup and 3 samples with two serogroups. No Salmonella serogroups were detected from WCR samples after immersion chilling with 20 mg/liter free chlorine. The 36 Salmonella-positive WCE samples included 21 samples with one serogroup and 15 samples with two serogroups. NS and WCE sampling methodologies yielded similar prevalence and serogroup diversity after air chilling. However, after immersion chilling with or without chlorine, WCE sampling yielded significantly higher (alpha <= 0.05) prevalence and serogroup diversity than either NS or WCR sampling methodologies. PMID- 26555516 TI - Salmonella Levels in Turkey Neck Skins, Drumstick Bones, and Spleens in Relation to Ground Turkey. AB - The objective of this study was to determine Salmonella levels (presence and numbers) in turkey drumstick bone, spleen, and neck skin samples in relation to Salmonella contamination levels in ground turkey at the flock level. Over a 10 month period, a total of 300 samples of each turkey part (i.e., neck skin, spleen, and drumstick) from 20 flocks were collected at a commercial turkey processing plant after the evisceration step. Turkey flocks included in this study were classified as "targeted" and "nontargeted" based on the company's historical ground turkey contamination data. A flock that originated from a turkey farm that had previously produced one or more flocks with >=20% Salmonella prevalence in ground turkey was labeled as a targeted flock (n = 13). The remaining seven flocks with <20% prevalence were labeled as nontargeted. All samples collected were tested for Salmonella presence and numbers by using most probable-number and selective enrichment methods. Further genotypic analysis (pulsed-field gel electrophoresis) of the isolates was performed. Ground turkey samples were collected and analyzed for Salmonella levels by the cooperating turkey company. The outside surface of bone and spleen were sterilized prior to Salmonella analysis. The overall Salmonella prevalence in neck skin, drumstick bone, spleen, and ground turkey samples was 42.0, 9.3, 6.7, and 14.5%, respectively. Salmonella prevalence in neck skin, spleen, drumstick bone, and ground turkey from the targeted flocks was significantly (P < 0.05) higher than those from nontargeted flocks. There was a significant relationship between Salmonella presence in neck skin (when most probable numbers were >=2 log) and Salmonella-positive ground turkey lot. Based on our findings, Salmonella was detected internally in drumstick bones and spleens at low levels, whereas Salmonella presence at higher levels in neck skin may indicate a flock with greater potential for Salmonella contamination of ground turkey. PMID- 26555517 TI - Survival of Salmonella during Drying of Fresh Ginger Root (Zingiber officinale) and Storage of Ground Ginger. AB - The survival of Salmonella on fresh ginger root (Zingiber officinale) during drying was examined using both a laboratory oven at 51 and 60 degrees C with two different fan settings and a small commercially available food dehydrator. The survival of Salmonella in ground ginger stored at 25 and 37 degrees C at 33% (low) and 97% (high) relative humidity (RH) was also examined. To inoculate ginger, a four-serovar cocktail of Salmonella was collected by harvesting agar lawn cells. For drying experiments, ginger slices (1 +/- 0.5 mm thickness) were surface inoculated at a starting level of approximately 9 log CFU/g. Higher temperature (60 degrees C) coupled with a slow fan speed (nonstringent condition) to promote a slower reduction in the water activity (aw) of the ginger resulted in a 3- to 4-log reduction in Salmonella populations in the first 4 to 6 h with an additional 2- to 3-log reduction by 24 h. Higher temperature with a higher fan speed (stringent condition) resulted in significantly less destruction of Salmonella throughout the 24-h period (P < 0.001). Survival appeared related to the rate of reduction in the aw. The aw also influenced Salmonella survival during storage of ground ginger. During storage at 97% RH, the maximum aw values were 0.85 at 25 degrees C and 0.87 at 37 degrees C; Salmonella was no longer detected after 25 and 5 days of storage, respectively, under these conditions. At 33% RH, the aw stabilized to approximately 0.35 at 25 degrees C and 0.31 at 37 degrees C. Salmonella levels remained relatively constant throughout the 365-day and 170-day storage periods for the respective temperatures. These results indicate a relationship between temperature and aw and the survival of Salmonella during both drying and storage of ginger. PMID- 26555518 TI - Growth of Stressed Strains of Four Non-O157 Shiga Toxin-Producing Escherichia coli Serogroups in Five Enrichment Broths. AB - The purpose of this study was to evaluate (i) the behavior of several strains of non-O157 Shiga toxin-producing Escherichia coli (STEC) serogroups (O26, O103, O111, and O145) exposed to different stress conditions and (ii) the growth dynamics of stressed and nonstressed non-O157 STEC cells in five enrichment media. STEC strains were exposed to acid, cold, and freeze stresses. Lethal and sublethal injuries were determined by plating in parallel on selective and nonselective agar media. Freeze stress (8 days, 20 degrees C) caused the most lethal (95.3% +/- 2.5%) injury, as well as the most sublethal (89.1% +/- 8.8%) injury in the surviving population. Growth of stressed and nonstressed pure cultures of non-O157 STEC on modified tryptic soy broth, buffered peptone water (BPW), BPW with sodium pyruvate, Brila, and STEC enrichment broth (SEB) was determined using total viable counts. To compare growth capacities, growth after 7 and 24 h of enrichment was measured; lag phases and maximum growth rates were also calculated. In general, growth on BPW resulted in a short lag phase followed by a high maximum growth rate during the enrichment of all tested strains when using all three stress types. Furthermore, BPW ensured the highest STEC count after 7 h of growth. Supplementing the medium with sodium pyruvate did not improve the growth dynamics. The two selective media, Brila and SEB, were less efficient than BPW, but Brila's enrichment performance was remarkably better than that of SEB. This study shows that irrespective of the effect of background flora, BPW is still recommended for resuscitation of non-O157 STEC. PMID- 26555519 TI - Antimicrobial Efficacy of a Sulfuric Acid and Sodium Sulfate Blend, Peroxyacetic Acid, and Cetylpyridinium Chloride against Salmonella on Inoculated Chicken Wings. AB - Studies were conducted to evaluate the efficacy of a commercial blend of sulfuric acid and sodium sulfate (SSS) in reducing Salmonella on inoculated whole chilled chicken wings and to compare its efficacy to peroxyacetic acid (PAA) and cetylpyridinium chloride (CPC). Wings were spot inoculated (5 to 6 log CFU/ml of sample rinsate) with a five-strain mixture of novobiocin- and nalidixic acid resistant Salmonella and then left untreated (control) or treated by immersing individual wings in 350 ml of antimicrobial solution. An initial study evaluated two treatment immersion times, 10 and 20 s, of SSS (pH 1.1) and compared cell recoveries following rinsing of treated samples with buffered peptone water or Dey/Engley neutralizing broth. In a second study, inoculated wings were treated with SSS (pH 1.1; 20 s), PAA (700 ppm, 20 s), or CPC (4,000 ppm, 10 s) and analyzed for survivors immediately after treatment (0 h) and after 24 h of aerobic storage at 4 degrees C. Color and pH analyses were also conducted in the latter study. Recovery of Salmonella survivors following treatment with SSS (10 or 20 s) was not (P >= 0.05) affected by the type of cell recovery rinse solution (buffered peptone water or Dey/Engley neutralizing broth), but there was an effect (P < 0.05) of SSS treatment time. Immersion of samples for 10 or 20 s in SSS resulted in pathogen reductions of 0.8 to 0.9 and 1.1 to 1.2 log CFU/ml, respectively. Results of the second study showed that there was an interaction (P < 0.05) between antimicrobial type and storage time. Efficacy against Salmonella at 0 h increased in the order CPC , SSS , PAA; however, after 24 h of aerobic storage, pathogen counts of SSS- and PAA-treated wings did not differ (P >= 0.05). Overall, the results indicated that SSS applied at pH 1.1 for 20 s was an effective antimicrobial intervention to reduce Salmonella contamination on chicken wings. PMID- 26555520 TI - Microbiological Quality of Seafood Marketed in Taiwan. AB - Seafood is often associated with foodborne illnesses, and Vibrio parahaemolyticus is the most common pathogen implicated in outbreaks in Taiwan. In this study, the microbiological quality of 300 raw or mixed ready-to-eat (RTE) and other cooking needed seafood samples was examined. The total aerobic and coliform counts of the RTE samples were significantly higher than those of other cooking-needed samples. On average, 55.8 and 29.7% of the RTE samples failed to meet the local microbiological standards for total aerobic (5 log CFU/g) and coliform (3 log most probable number [MPN] per g), counts respectively; the corresponding percentages for the RTE samples from Taipei City were 9.1 and 18.2%, respectively. The total aerobic and coliform counts in the RTE samples from supermarkets and chain restaurants were significantly lower than those from traditional restaurants. The Vibrio species were more frequently identified in the cooking-needed samples than in RTE samples. Low incidences of V. parahaemolyticus (1.4%), V. vulnificus (1.9%), and V. cholerae (0%) were detected in most RTE samples. High densities of V. parahaemolyticus and V. vulnificus (1,200 MPN/g) were detected in a few RTE samples, only one of which contained toxigenic (tdh(+)) V. parahaemolyticus. The results of this investigation reveal that better hygiene of seafood providers such as chain restaurants, supermarkets, and traditional restaurants in Taipei City would effectively improve the microbiological quality of the seafood. The results will facilitate the establishment of measures for controlling the risks associated with seafood in Taiwan. PMID- 26555521 TI - Comparison of the Microbial Quality of Lamb and Goat Meat Acquired from Internet and Local Retail Markets. AB - This study was conducted to evaluate the microbial quality of lamb and goat meat sold through local (Virginia) and Internet (U. S.) retail markets. A total of 134 frozen meat products consisting of locally purchased lamb ground (LLG) and lamb chops and Internet-procured lamb ground, goat ground, lamb chops (ILC), goat chops (IGC), lamb stew, and goat stew were tested. Significantly higher levels of aerobic mesophiles, psychrotrophs, and coliforms were found in the meat locally acquired than in the meat procured from the Internet. Similar average prevalence (27%) of Escherichia coli was observed regardless of market source. Ground meat had significantly high levels and prevalence of mesophiles, psychrotrophs, coliforms, and Listeria spp. One sample of LLG contained Campylobacter, and one sample of IGC contained Salmonella. Listeria spp. were present in 23 to 40% and 17 to 80% of samples from local and Internet markets, respectively. Pulsed-field gel electrophoresis (PFGE) of isolated E. coli strains revealed brand specificity and genomic diversity. No isolate from different brands and market sources had matching PFGE profiles. The average price of Internet meat ($23.4/kg) was about 1.2 times higher than the price of local meat, except for ILC, whose price was 2.7 times higher. This study revealed differences in microbial quality of lamb and goat meat based on market source; thus, meat products should be handled carefully regardless of market source because of the presence of high microbial levels and the high prevalence of pathogens. PMID- 26555522 TI - Predominance and Distribution of a Persistent Listeria monocytogenes Clone in a Commercial Fresh Mushroom Processing Environment. AB - A longitudinal study was conducted to determine the prevalence of Listeria spp. in a commercial fresh mushroom slicing and packaging environment. Samples were collected at three different sampling periods within a 13-month time interval. Of the 255 environmental samples collected, 18.8% tested positive for L. monocytogenes, 4.3% for L. innocua, and 2.0% for L. grayi. L. monocytogenes was most often found on wet floors within the washing and slicing and packaging areas. Each of the 171 L. monocytogenes isolates found in the environment could be placed into one of three different serotypes; 1/2c was predominant (93.6%), followed by 1/2b (3.5%) and 1/2a (2.9%). Of 58 isolates subtyped using multi virulence-locus sequence typing, all 1/2c isolates were identified as virulence type (VT) 11 (VT11), all 1/2b isolates were VT105, and 1/2a isolates were either VT107 or VT56. VT11 was designated as the predominant and persistent clone in the environment because it was isolated repeatedly at numerous locations throughout the study. The overall predominance and persistence of VT11 indicates that it likely colonized the mushroom processing environment. Areas adjacent to the trench drain in the washing and slicing area and a floor crack in the packaging area may represent primary harborage sites (reservoirs) for VT11. Improvements made to sanitation procedures by company management after period 2 coincided with a significant (P <= 0.001) reduction in the prevalence of L. monocytogenes from 17.8% in period 1 and 30.7% in period 2 to 8.5% in period 3. This suggests that targeted cleaning and sanitizing procedures can be effective in minimizing the occurrence of L. monocytogenes contamination in processing facilities. Additional research is needed to understand why VT11 was predominant and persistent in the mushroom processing environment. PMID- 26555523 TI - Prevalence of Staphylococcus aureus in Imported Fish and Correlations between Antibiotic Resistance and Enterotoxigenicity. AB - A total of 156 Staphylococcus aureus isolates were obtained from 330 imported fresh fish samples from three countries. Selective media were used for the isolation of S. aureus, and the isolates were confirmed by PCR. The isolates were tested for mecA gene, antibiotic resistance, and enterotoxin genes (sea, seb, sec, sed, see, seg, seh, and sei). Most isolates carried sea, seg, and sei genes, and seg-sei was the most frequent enterotoxin profile. About 88.5% of the S. aureus exhibited resistance to at least one antibiotic. High resistance to penicillin and ampicillin; low resistance to tetracycline, erythromycin, rifampin, and clindamycin; and very low resistance to cefotaxime, amoxicillin clavulanic acid, gentamicin, and ciprofloxacin were exhibited by S. aureus from the three countries. In addition, some antibiotic resistance exhibited a strong correlation (P <= 0.01) with enterotoxigenicity in S. aureus. The study concluded that the large amount of globally traded fish increases the possibility of intercontinental transmission of enterotoxigenic and multidrug-resistant S. aureus through fish and highlights the potential influence of local fish handling and processing on consumer health worldwide. The introduction of periodic training in food safety and hygiene is essential to increase fish handlers' awareness of good hygienic practices in handling fish. These findings also enrich the ongoing debate about the risk of methicillin- and multidrug-resistant S. aureus as a foodborne pathogen compared with drug-susceptible S. aureus. PMID- 26555524 TI - Clostridium botulinum Toxin Production in Relation to Spoilage of Atlantic Salmon (Salmo salar) Packaged in Films of Varying Oxygen Permeabilities and with Different Atmospheres. AB - Shelf life of fish packaged under modified atmosphere (MA) is extended, but within the United States, commercial application of MA with impermeable packaging films is restricted due to concerns that botulinum toxin production would precede spoilage when contaminated fish are held at abusive storage temperatures. Use of semipermeable packaging films has been advocated; however, previous studies are inconclusive in determining the oxygen transmission rate (OTR) of a film that is needed to achieve an acceptable margin of safety (i.e., toxin production occurs only after spoilage). This study was conducted to determine the influence of OTR (target OTRs of 3 to 15,000) on the development of spoilage volatiles and toxin in salmon inoculated with type E Clostridium botulinum and subjected to air, vacuum, or 75:25 CO2:N2 MA and storage temperatures of 4, 8, 12, or 16 degrees C. The most dominant headspace volatile peak that was produced during spoilage of samples at 4, 8 or 12 degrees C was a peak, having a Kovats retention index (KI) of 753, and at which external standards of 2- or 3-methyl 1-butanol also eluted. Under anaerobic conditions, both the aerobic microbial populations and the size of the KI 753 spoilage peak were less in inoculated samples compared with uninoculated samples. C. botulinum-inoculated samples that were stored at 12 or 16 degrees C under conditions favorable for anaerobic growth were also characterized by a KI 688 peak. Using a previously developed model that related the percentage of elderly consumers who would prepare a sample having the KI 753 spoilage peak of a specific size, it was determined that for salmon packaged with 3 or 3,000 OTR films under any atmosphere and stored at 12 or 16 degrees C, 2 to 61% of the consumers could potentially prepare toxin-contaminated samples. Hence, when abusive storage conditions are suspected, the fish should not be consumed. PMID- 26555525 TI - Effect of Nisin and Thermal Treatments on the Heat Resistance of Clostridium sporogenes Spores. AB - The aim of this research was to evaluate the effect of thermal treatments (isothermal or nonisothermal) combined with nisin, a natural antimicrobial, on the survival and recovery of Clostridium sporogenes spores. The addition of nisin to the heating medium at concentrations up to 0.1 mg liter(-1) did not reduce the heat resistance of C. sporogenes. Without a thermal treatment, nisin added at concentrations up to 0.1 mg liter(-1) did not reduce the viable counts of C. sporogenes when added to the recovery medium, but inactivation of more than 4 log cycles was achieved after only 3 s at 100 degrees C. At 100 degrees C, the time needed to reduce viable counts by more than 3 log cycles was nine times shorter when 0.01 mg liter(-1) nisin was added to the recovery medium than without it. The heat resistance values calculated under isothermal conditions were used to predict the survival in the nonisothermal experiments, and the predicted values accurately fit the experimental data. The combination of nisin with a thermal treatment can help control C. sporogenes. PMID- 26555526 TI - Ability of Hand Hygiene Interventions Using Alcohol-Based Hand Sanitizers and Soap To Reduce Microbial Load on Farmworker Hands Soiled during Harvest. AB - Effective hand hygiene is essential to prevent the spread of pathogens on produce farms and reduce foodborne illness. The U.S. Food and Drug Administration Food Safety Modernization Act Proposed Rule for Produce Safety recommends the use of soap and running water for hand hygiene of produce handlers. The use of alcohol based hand sanitizer (ABHS) may be an effective alternative hygiene intervention where access to water is limited. There are no published data on the efficacy of either soap or ABHS-based interventions to reduce microbial contamination in agricultural settings. The goal of this study was to assess the ability of two soap-based (traditional or pumice) and two ABHS-based (label-use or two-step) hygiene interventions to reduce microbes (coliforms, Escherichia coli, and Enterococcus spp.) and soil (absorbance of hand rinsate at 600 nm [A600]) on farmworker hands after harvesting produce, compared with the results for a no hand-hygiene control. With no hand hygiene, farmworker hands were soiled (median A600, 0.48) and had high concentrations of coliforms (geometric mean, 3.4 log CFU per hand) and Enterococcus spp. (geometric mean, 5.3 log CFU per hand) after 1 to 2 h of harvesting tomatoes. Differences in microbial loads in comparison to the loads in the control group varied by indicator organism and hygiene intervention (0 to 2.3 log CFU per hand). All interventions yielded lower concentrations of Enterococcus spp. and E. coli (P < 0.05), but not of coliforms, than were found in the control group. The two-step ABHS intervention led to significantly lower concentrations of coliforms and Enterococcus spp. than the pumice soap and label use ABHS interventions (P < 0.05) and was the only intervention to yield significantly fewer samples with E. coli than were found in the control group (P < 0.05). All interventions removed soil from hands (P < 0.05), soap-based interventions more so than ABHS-based interventions (P < 0.05). ABHS-based interventions were equally as effective as hand washing with soap at reducing indicator organisms on farmworker hands. Based on these results, ABHS is an efficacious hand hygiene solution for produce handlers, even on soiled hands. PMID- 26555527 TI - Evaluating North Carolina Food Pantry Food Safety-Related Operating Procedures. AB - Almost one in seven American households were food insecure in 2012, experiencing difficulty in providing enough food for all family members due to a lack of resources. Food pantries assist a food-insecure population through emergency food provision, but there is a paucity of information on the food safety-related operating procedures used in the pantries. Food pantries operate in a variable regulatory landscape; in some jurisdictions, they are treated equivalent to restaurants, while in others, they operate outside of inspection regimes. By using a mixed methods approach to catalog the standard operating procedures related to food in 105 food pantries from 12 North Carolina counties, we evaluated their potential impact on food safety. Data collected through interviews with pantry managers were supplemented with observed food safety practices scored against a modified version of the North Carolina Food Establishment Inspection Report. Pantries partnered with organized food bank networks were compared with those that operated independently. In this exploratory research, additional comparisons were examined for pantries in metropolitan areas versus nonmetropolitan areas and pantries with managers who had received food safety training versus managers who had not. The results provide a snapshot of how North Carolina food pantries operate and document risk mitigation strategies for foodborne illness for the vulnerable populations they serve. Data analysis reveals gaps in food safety knowledge and practice, indicating that pantries would benefit from more effective food safety training, especially focusing on formalizing risk management strategies. In addition, new tools, procedures, or policy interventions might improve information actualization by food pantry personnel. PMID- 26555528 TI - Evaluation of the Implementation of Good Handling Practices in Food and Beverage Areas of Hotels. AB - Because of the major international-level events that have recently been held in Brazil, concerns about the sensory and hygienic-sanitary conditions of food have increased. The objective of this study was to evaluate the implementation of good handling practices in food and beverage areas of hotels, with and without outsourced professional intervention. We evaluated 19 food and beverage areas in hotels in Porto Alegre, Rio do Sul, Brazil, using a checklist that was developed by a municipal surveillance team based on existing laws for good handling practices. The evaluation was done by a skilled professional in the food safety area on two occasions, at the beginning of the study (January to May 2013) and at the end (July to November 2014), and the establishments were classified as good, regular, or poor. After the baseline evaluation, an action plan listing the noncompliance found at each location was given to those responsible for the establishments, and a period of 1 year 6 months was stipulated for improvements to be made. In the repeat evaluation, those responsible for the establishments were asked whether they had hired an outsourced professional to assist them in the improvements. The hotels showed improvement during the repeat evaluation, but a significant increase in the percentage of overall adequacy was seen only in the food and beverages areas of the 12 hotels that used the intervention of an outsourced professional. The better percentage of adequacy in establishments with outsourced professional intervention underlines the importance of an external and impartial view of routine activities in the implementation of good handling practices. PMID- 26555529 TI - Detection of Zygosaccharomyces rouxii and Candida tropicalis in a High-Sugar Medium by a Metal Oxide Sensor-Based Electronic Nose and Comparison with Test Panel Evaluation. AB - Osmotolerant yeasts are primarily responsible for spoilage of sugar-rich foods. In this work, an electronic nose (e-nose) was used to diagnose contamination caused by two osmotolerant yeast strains (Zygosaccharomyces rouxii and Candida tropicalis) in a high-sugar medium using test panel evaluation as the reference method. Solid-phase microextraction gas chromatography with mass spectrometry (GC MS) was used to determine the evolution of the volatile organic compound fingerprint in the contaminated samples during yeast growth. Principal component analysis and linear discriminant analysis revealed that the e-nose could identify contamination after 48 h, corresponding to the total yeast levels of 3.68 (Z. rouxii) and 3.09 (C. tropicalis) log CFU/ml. At these levels, the test panel could not yet diagnose the spoilage, indicating that the e-nose approach was more sensitive than the test panel evaluation. Loading analysis indicated that sensors 8 and 6 were the most important for detection of these two yeasts. Based on the result obtained with the e-nose, the incubation time and total yeast levels could be accurately predicted by established multiple regression models with a correlation of greater than 0.97. In the sensory evaluation, spoilage was diagnosed after 72 h in samples contaminated with C. tropicalis and after 48 to 72 h for samples contaminated with Z. rouxii. GC-MS revealed that compounds such as acetaldehyde, acetone, ethyl acetate, alcohol, and 3-methyl-1-butanol contributed to spoilage detection by the e-nose after 48 h. In the high-sugar medium, the e-nose was more sensitive than the test panel evaluation for detecting contamination with these test yeast strains. This information could be useful for developing instruments and techniques for rapid scanning of sugar-rich foods for contamination with osmotolerant yeasts before such spoilage could be detected by the consumer. PMID- 26555530 TI - Retention of Rotavirus Infectivity in Mussels Heated by Using the French Recipe Moules Marinieres. AB - To evaluate the persistence of infectious virus after heating, mussels contaminated with a rotavirus strain were prepared following the French recipe moules marinieres (mariner's mussels). Rotavirus was then quantified by real-time quantitative PCR (RT-qPCR) and a cell culture infectivity assay. Results showed the persistence of infectious virus after 3 min of cooking. After 5 min, when no infectious virus could be detected, the RT-qPCR approach showed a 1-log decrease compared with concentrations detected after 1 min of cooking. PMID- 26555531 TI - When Vacant Lots Become Urban Gardens: Characterizing the Perceived and Actual Food Safety Concerns of Urban Agriculture in Ohio. AB - This study was intended to characterize the perceived risks of urban agriculture by residents of four low-income neighborhoods in which the potential exists for further urban agriculture development and to provide data to support whether any chemical hazards and foodborne pathogens as potential food safety hazards were present. Sixty-seven residents participated in focus groups related to environmental health, food security, and urban gardening. In addition, soils from six locations were tested. Residents expressed interest in the development of urban gardens to improve access to healthy, fresh produce, but they had concerns about soil quality. Soils were contaminated with lead (Pb), zinc, cadmium (Cd), and copper, but not arsenic or chromium. Results from our study suggest paint was the main source of soil contamination. Detectable polyaromatic hydrocarbon (PAH) levels in urban soils were well below levels of concern. These urban soils will require further management to reduce Pb and possibly Cd bioavailability to decrease the potential for uptake into food crops. Although the number of locations in this study is limited, results suggest lower levels of soil contaminants at well-established gardens. Soil tillage associated with long-term gardening could have diluted the soil metal contaminants by mixing the contaminants with clean soil. Also, lower PAH levels in long-term gardening could be due to enhanced microbial activity and PAH degradation, dilution, or both due to mixing, similar to metals. No foodborne pathogen targets were detected by PCR from any of the soils. Residents expressed the need for clearness regarding soil quality and gardening practices in their neighborhoods to consume food grown in these urban areas. Results from this study suggest long-term gardening has the potential to reduce soil contaminants and their potential threat to food quality and human health and to improve access to fresh produce in low-income urban communities. PMID- 26555532 TI - Investigation into Possible Differences in Salmonella Prevalence in the Peripheral Lymph Nodes of Cattle Derived from Distinct Production Systems and of Different Breed Types. AB - Previous research demonstrated significant variation in the prevalence of Salmonella in peripheral lymph nodes (LNs) of feedlot cattle and cull cows, with greater prevalence in feedlot cattle. Therefore, we performed experiments to investigate whether these differences in Salmonella prevalence in subiliac LNs are due to, or influenced by, breed, which in many respects is a proxy for the production system in which the animal is derived. Holstein steers are a by product of dairy systems, and beef steers are an intended product of commercial beef operations. For the first experiment, Holstein and beef steers originating from the same feedlot and harvested on the same day were sampled. Of the 467 Holstein and 462 beef cattle LNs collected, 62.1% of Holstein and 59.7% of beef cattle samples harbored Salmonella (P = 0.46; qualitative culture), with 51.2 and 48.9% of samples containing quantifiable concentrations (P = 0.49), respectively. The concentration of Salmonella within the LN followed a decreasing trend over the collection period (May to October), averaging 1.4 log CFU/g of LN for both Holstein and beef cattle samples (P = 0.78). In a second experiment, we compared 100% Brahman cattle to their beef cattle counterparts, as we hypothesized that the resistance of Brahman cattle to insects may reduce Salmonella transmission via biting insects. Of the 42 Brahman and 31 beef cattle LNs collected, the concentration of Salmonella within the LN averaged 3.0 log CFU/g for Brahman cattle and 2.9 log CFU/g for beef cattle samples (P = 0.30). Using qualitative culture, we recovered Salmonella from 100% of LNs from Brahman cattle and 97% of beef cattle samples (P = 0.25). Results of this research indicate that the differences observed are not due to breed and are likely a function of age, immune function, or other factors yet to be identified. Understanding which cattle are more likely to harbor Salmonella within LNs will aid in targeting both pre- and postharvest intervention strategies. PMID- 26555533 TI - Virulence Potential of Activatable Shiga Toxin 2d-Producing Escherichia coli Isolates from Fresh Produce. AB - Shiga toxin (Stx)-producing Escherichia coli (STEC) strains are food- and waterborne pathogens that are often transmitted via beef products or fresh produce. STEC strains cause both sporadic infections and outbreaks, which may result in hemorrhagic colitis and hemolytic uremic syndrome. STEC strains may elaborate Stx1, Stx2, and/or subtypes of those toxins. Epidemiological evidence indicates that STEC that produce subtypes Stx2a, Stx2c, and/or Stx2d are more often associated with serious illness. The Stx2d subtype becomes more toxic to Vero cells after incubation with intestinal mucus or elastase, a process named "activation." Stx2d is not generally found in the E. coli serotypes most commonly connected to STEC outbreaks. However, STEC strains that are stx2d positive can be isolated from foods, an occurrence that gives rise to the question of whether those food isolates are potential human pathogens. In this study, we examined 14 STEC strains from fresh produce that were stx2d positive and found that they all produced the mucus-activatable Stx2d and that a subset of the strains tested were virulent in streptomycin-treated mice. PMID- 26555534 TI - Prevalence and Antimicrobial Resistance of Vibrio spp. in Retail and Farm Shrimps in Ecuador. AB - The aim of this study was to investigate the prevalence of Vibrio spp. in shrimp at retail and in shrimp farms in Ecuador and to determine the antimicrobial agent resistance patterns of farm isolates. The presence of genes linked to early mortality syndrome (EMS) or acute hepatopancreatic necrosis disease (AHPND) also was evaluated. Vibrio spp. were isolated from retail shrimps in Cuenca, Ecuador, and farm shrimps originating from provinces El Oro and Guayas, Ecuador. A total of 229 shrimp samples were collected, of which 71 originated from retail markets in Cuenca and 158 came from shrimp farms. Overall, 219 (95.6%) samples tested positive for Vibrio spp. Vibrio parahaemolyticus (80.8%) was the most common species detected, followed by Vibrio alginolyticus (50.2%), Vibrio cholerae (11.3%), and Vibrio vulnificus (3.5%). None of the V. parahaemolyticus isolates carried the virulence-associated tdh and trh genes. In V. parahaemolyticus shrimp farm isolates, high resistance was found to ampicillin (92.2%), and intermediate resistance was found to tetracycline (51.3%) and amikacin (22.1%). Of the V. parahaemolyticus strains, 68 were resistant to at least three antimicrobial agents, and 2 were resistant to seven antimicrobial agents simultaneously. Up to 18 resistant isolates were found for V. alginolyticus, whereas V. vulnificus and V. cholerae isolates were more susceptible. None of the V. parahaemolyticus isolates carried the EMS-AHPND plasmid. The results of this study revealed the ubiquitous occurrence of Vibrio spp. in shrimps at retail and on shrimp farms in Ecuador. PMID- 26555535 TI - Prevalence of Foodborne Pathogens in Freshwater Fish in Latvia. AB - The aim of this study was to detect the prevalence of Salmonella spp., Listeria monocytogenes, and Yersinia enterocolitica in freshwater fish in Latvia. In total, 235 samples, including freshly caught fish from fives lakes (n = 129) and fish from retail markets (n = 106), were collected from April 2014 to December 2014 in Latvia. Samples were tested according to International Organization for Standardization methods. No Salmonella spp. were found in fresh fish from lakes or in commercially available fish. In contrast, the overall prevalence of L. monocytogenes and Y. enterocolitica in freshwater fish was 13% (30 of 235) and 14% (34 of 235), respectively, and no significant difference between the prevalence of L. monocytogenes and Y. enterocolitica was observed (P > 0.05). All Y. enterocolitica isolates belonged to the nonpathogenic 1A biotype. Molecular serotyping of L. monocytogenes revealed that the most distributed serogroup was 1/2a-3a (65%), followed by 1/2c-3c (25%), 1/2b-3b (5%), and 4b, 4d, 4e (5%). The prevalence of L. monocytogenes and Y. enterocolitica in freshwater lake fish was 2% (2 of 129) and 3% (4 of 129), respectively. In contrast, the prevalence of L. monocytogenes and Y. enterocolitica in fish at retail markets was 26% (28 of 106) and 28% (30 of 106), respectively. In retail samples, 9 of 58 positive fish contained both L. monocytogenes and Y. enterocolitica. In general, differences in the prevalences of L. monocytogenes and Y. enterocolitica in retail samples were significantly higher than those in freshly caught fish (P < 0.05). The results of this study indicate that freshwater fish could be an important source of Y. enterocolitica and L. monocytogenes for consumers in Latvia. PMID- 26555536 TI - Serological and Molecular Investigation of Swine Hepatitis E Virus in Pigs Raised in Southern Italy. AB - Hepatitis E virus (HEV) infection is a common acute hepatitis transmitted by the fecal-oral route. In developed countries, the virus has a zoonotic potential, and domestic pigs and wild boars are considered main reservoirs. To assess the prevalence of HEV-positive animals in the Calabria region (southern Italy) on a serological and molecular level, a total of 216 autochthonous healthy pigs (Apulo Calabrese breed) were sampled. Both sera and feces were collected. Pigs were grouped based on age: 117 pigs <6 months and 99 pigs >6 months. By using a commercial enzyme-linked immunosorbent assay system, a total of 173 (80%) of the 216 pigs tested seropositive. In all sampled farms (n = 8), pigs with antibodies (immunoglobulin G) against HEV were detected at a level higher than 60%, with a significant difference among age groups (P < 0.0001). Moreover, 16 fattening pigs were found to be nested reverse transcription PCR positive and thus to shed viral genomes in their feces. These positive findings resulted in a prevalence of 48.4% on the farm level (16 of 35 pigs) and an overall prevalence of 7.4% at the animal level (16 of 216 pigs). Based on the present study, HEV seems to circulate among the autochthonous domestic pig population of southern Italy with a low sharing rate. Further studies exploring the origin of infection are needed to minimize the risk of human exposure and to reduce consequences for public health. PMID- 26555537 TI - Major Greenwood (1880-1949): a biographical and bibliographical study. AB - Major Greenwood was the foremost medical statistician of the first half of the 20th century in the U.K. Trained in both medicine and statistics, his career extended over 45 years during which he published eight books, 23 extensive reports and over 200 papers. His classical education extended to Latin and Greek, and he was fluent in German and French. We provide an overview of his life including family background, training and his career subdivided according to the places where he worked. We describe in particular the key role he played with others in the development of medical statistics within the Medical Research Council, the General Register Office, the Department of Health and the Universities. PMID- 26555541 TI - Analysis of Genomic DNAs from Nine Rosaceae Species Using Surface-Enhanced Raman Scattering. AB - Surface-enhanced Raman scattering (SERS) of genomic DNA was used to determine genetic relationships and species identification of nine plants from three subfamilies of Rosaceae. Genomic DNA was extracted, and the SERS spectra were obtained by using a nanosilver collosol at an excitation wavelength of 785 nm. Adenine and ribodesose were the active sites of genomic DNAs in the silver surface-enhanced Raman spectra. The strong peak at 714 cm(-1) was assigned to the stretching vibration of adenine, the strong peak at 1011cm(-1) contributed to the stretching vibration of the deoxyribose and the scissoring vibrations of cytosine, and the strong peak at 625 cm(-1) is the stretching vibration of glycosidic bond and the scissoring vibrations of guanine. The three-dimensional plot of the first, second, and third principal components showed that the nine species could be classified into three categories (three subfamilies), consistent with the traditional classification. The model of the hierarchical cluster combined with the principal component of the second derivative was more reasonable. The results of the cluster analysis showed that apricot (Prunus armeniaca L.) and cherry (Prunus seudocerasus Lindl.) were clustered into one category (Prunoideae); firethorn (Firethorn fortuneana Li.), loquat (Eriobotrya japonica Lindl.), apple (Malus pumila Mill.), and crabapple (Malus hallianna Koehne.) were clustered into a second category (Pomoideae); and potentilla (Potentilla fulgens Wall.), rose (Rosa chinensis Jacd.), and strawberry (Fragaria chiloensis Duchesne.) were clustered into a third category (Rosoideae). These classifications were in accordance with the traditional classification with a correction rate of clustering of 100%. The correct rate of species identification was 100%. These five main results indicate that the genetic relationship and species identification of nine Rosaceae species could be determined by using SERS spectra of their genomic DNAs. PMID- 26555543 TI - Nisin is an effective inhibitor of Clostridium difficile vegetative cells and spore germination. AB - Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomial antibiotic-associated diarrhoea and pseudomembranous colitis. Several clinically isolated C. difficile strains are resistant to antibiotics other than metronidazole and vancomycin. Recently, bacteriocins of lactic acid bacteria have been proposed as an alternative or complementary treatment. The aim of this study was to investigate the inhibitory effect of nisin, a bacteriocin produced by several strains of Lactococcus lactis, against clinical isolates of C. difficile. Nisin Z obtained from culture of L. lactis subsp. lactis biovar. diacetylactis was tested along with commercial nisin A. The effect of nisin A on C. difficile spores was also examined. Nisin A and Z both inhibited the growth of all C. difficile isolates, and MICs were estimated at 6.2 MUg ml(-1) for nisin Z and 0.8 MUg ml(-1) for nisin A. In addition, C. difficile spores were also susceptible to nisin A (25.6 MUg ml(-1)), which reduced spore viability by 40-50%. These results suggested that nisin and hence nisin-producing Lactococcus strains could be used to treat C. difficile-associated diarrhoea. PMID- 26555542 TI - Distinct functions of two olfactory marker protein genes derived from teleost specific whole genome duplication. AB - BACKGROUND: Whole genome duplications (WGDs) have been proposed to have made a significant impact on vertebrate evolution. Two rounds of WGD (1R and 2R) occurred in the common ancestor of Gnathostomata and Cyclostomata, followed by the third-round WGD (3R) in a common ancestor of all modern teleosts. The 3R derived paralogs are good models for understanding the evolution of genes after WGD, which have the potential to facilitate phenotypic diversification. However, the recent studies of 3R-derived paralogs tend to be based on in silico analyses. Here we analyzed the paralogs encoding teleost olfactory marker protein (OMP), which was shown to be specifically expressed in mature olfactory sensory neurons and is expected to be involved in olfactory transduction. RESULTS: Our genome database search identified two OMPs (OMP1 and OMP2) in teleosts, whereas only one was present in other vertebrates. Phylogenetic and synteny analyses suggested that OMP1 and 2 were derived from 3R. Both OMPs showed distinct expression patterns in zebrafish; OMP1 was expressed in the deep layer of the olfactory epithelium (OE), which is consistent with previous studies of mice and zebrafish, whereas OMP2 was sporadically expressed in the superficial layer. Interestingly, OMP2 was expressed in a very restricted region of the retina as well as in the OE. In addition, the analysis of transcriptome data of spotted gar, a non-teleost fish, revealed that single OMP gene was expressed in the eyes. CONCLUSION: We found distinct expression patterns of zebrafish OMP1 and 2 at the tissue and cellular level. These differences in expression patterns may be explained by subfunctionalization as the model of molecular evolution. Namely, single OMP gene was speculated to be originally expressed in the OE and the eyes in the common ancestor of all Osteichthyes (bony fish including tetrapods). Then, two OMP gene paralogs derived from 3R-WGD reduced and specialized the expression patterns. This study provides a good example for analyzing a functional subdivision of the teleost OE and eyes as revealed by 3R-derived paralogs of OMPs. PMID- 26555544 TI - A polysaccharide from pumpkin induces apoptosis of HepG2 cells by activation of mitochondrial pathway. AB - Purified white polysaccharide (PPW) is a homogenous polysaccharide isolated from pumpkin, with an average molecular weight of 34 kDa. In this study, we aimed at examining the anti-proliferative activity of PPW against hepatocellular carcinoma (HCC) HepG2 cells and the underlying mechanisms. We found that PPW-induced inhibition of cell proliferation in HepG2 cells was associated with the induction of apoptosis. Exposure of HepG2 cells to PPW (100, 200, and 400 MUg/mL) resulted in a loss of mitochondrial membrane potential (Deltapsim) and the release of cytochrome c from the mitochondria to the cytosol. Also, Western blot analysis revealed dose-dependent increase of pro-apoptotic Bax protein and decrease of anti-apoptotic Bcl-2 protein in PPW-treated cells. Besides, caspase-9 and caspase 3 activities were also enhanced in HepG2 cells followed by PPW treatment. Additionally, the cleavage of poly (ADP-ribose) polymerase (PARP) was observed in PPW-treated HepG2 cells, which altogether account for apoptotic cell death. These results suggested that PPW-induced apoptosis involved a caspase-3-mediated mitochondrial pathway and may have potential as a cancer chemopreventive and therapeutic agent for the prevention and treatment of HCC. PMID- 26555545 TI - Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs. AB - While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes. PMID- 26555546 TI - Long non-coding RNA MVIH is associated with poor prognosis and malignant biological behavior in breast cancer. AB - In recent years, with the development of transcriptomics, the effect of long non coding RNAs (LncRNAs) on the regulation of biological processes is being elucidated. LncRNAs play an important role in tumor occurrence and development. LncRNA associated with microvascular invasion in hepatocellular carcinoma (LncRNA MVIH) was first identified in hepatocellular carcinoma and is associated with angiogenesis, tumor growth and metastasis upregulation, and poor recurrence-free survival. MVIH has an important role in non-small cell lung cancer, in which it promotes cell proliferation and metastasis, and high MVIH expression indicates poor overall survival. However, the involvement of MVIH in breast cancer is unclear. Our research revealed that the expression levels of MVIH in breast cancer tissues were higher than in adjacent noncancerous tissues, and high MVIH expression was correlated with Ki67 expression. Moreover, breast cancer patients with high MVIH expression levels showed poor overall survival and disease-free survival. Multivariate analysis results indicated that MVIH was an independent prognostic factor in breast cancer. In addition, upregulated MVIH expression levels promoted cell proliferation and cell cycle, and inhibited cell apoptosis, while reduced MVIH expression showed the converse. In summary, our findings suggest that MVIH may have an important role in breast cancer and may serve as a new biomarker and a potential therapeutic target. PMID- 26555547 TI - A lateral approach defect closure technique with deep fascia flap for valgus knee TKA. AB - BACKGROUND: Routinely, we use a midline skin incision and lateral parapatellar approach of the knee to perform valgus knee TKA (total knee arthroplasty). It is generally very difficult to close the lateral capsular defect after valgus knee TKA, especially for severe valgus and flexion knee deformity. METHODS: We describe a new surgical technique to close the lateral capsular defect with a deep fascia flap. From 2009 to 2012, we used the new technique to close lateral capsular defects for nine valgus TKA in eight patients. The wound healing, infection, range of motion, and postoperative X-ray Laurien view were evaluated. RESULTS: According to follow-up, we found that this technique can reduce the risk of intra- and postoperative complications (exposure of knee prosthesis, larger subcutaneous hematoma, poor wound healing, and higher risk of infection) and improve clinical outcome of total knee replacement (good range of motion and patellar tracking). There is no need for lateral parapatellar capsule Z-plasty during incision or filling the distal capsular defect with fat pad or composite meniscal-capsular-fat pad. CONCLUSION: Closing lateral capsular defect with a deep fascia flap for valgus knee TKA through a lateral parapatellar approach is a new and effective surgical technique. PMID- 26555548 TI - Deficiency of inducible and endothelial nitric oxide synthase results in diminished bone formation and delayed union and nonunion development. AB - BACKGROUND: Between 5% and 10% of all fractures fail to heal adequately resulting in nonunion of the fracture fragments. This can significantly decrease a patient's quality of life and create associated psychosocial and socio-economic problems. Nitric oxide (NO) and nitric oxide synthases (NOS) have been found to be involved in fracture healing, but until now it is not known if disturbances in these mechanisms play a role in nonunion and delayed union development. In this study, we explored the role of endothelial and inducible NOS deficiency in a delayed union model in mice. MATERIALS AND METHODS: A 0.45mm femur osteotomy with periosteal cauterization followed by plate-screw osteosynthesis was performed in the left leg of 20-24week old wild type, Nos2(-/-) and Nos3(-/-) mice. Contralateral unfractured legs were used as a control. Callus volume was measured using micro-computed tomography (MUCT) after 28 and 42days of fracture healing. Immuno histochemical myeloperoxidase (MPO) staining was performed on paraffin embedded sections to assess neutrophil influx in callus tissue and surrounding proximal and distal marrow cavities of the femur. After 7 and 28days of fracture healing, femurs were collected for amino acid and RNA analysis to study arginine NO metabolism. RESULTS: With MUCT, delayed union was observed in wild type animals, whereas in both Nos2(-/-) and Nos3(-/-) mice nonunion development was evident. Both knock-out strains also showed a significantly increased influx of MPO when compared with wild type mice. Concentrations of amino acids and expression of enzymes related to the arginine-NO metabolism were aberrant in NOS deficient mice when compared to contralateral control femurs and wild type samples. DISCUSSION AND CONCLUSION: In the present study we show for the first time that the absence of nitric oxide synthases results in a disturbed arginine NO metabolism and inadequate fracture healing with the transition of delayed union into a nonunion in mice after a femur osteotomy. Based on these data we suggest that the arginine-NO metabolism may play a role in the prevention of delayed unions and nonunions. PMID- 26555549 TI - [Hypertrophic chondrocytes: Programmed cell death or stem cell reservoir?]. AB - The majority of bones in the vertebrate skeleton develop by endochondral ossification, a process during which an intermediate cartilage template is successively replaced by bone. Many aspects of this process are relatively well understood; nevertheless, the origin of trabecular bone-forming osteoblasts and mesenchymal stem cells of the stroma has long remained under debate. Until recently, progenitors of these cell types were thought to enter the bone-forming structures from the periosteum together with the invading vasculature. Recent unexpected results revealed, however, that under physiological conditions differentiated hypertrophic chondrocytes give rise to both, osteoblasts and mesenchymal progenitor cells, thereby contributing to the formation of trabecular bone and bone marrow. PMID- 26555550 TI - Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna. A case report of a patient with seronegative rheumatoid arthritis and rheumatoid vasculitis. AB - Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent. PMID- 26555551 TI - Relationship of osteoprotegerin to pulse wave velocity and carotid intima-media thickness in rheumatoid arthritis patients. AB - OBJECTIVE: Osteoprotegerin (OPG) is considered an important biomarker in cardiovascular (CV) disease. CV disease is the most common cause of mortality in patients with rheumatoid arthritis (RA), a consequence of accelerated atherosclerosis. The present study aimed to evaluate the relationship of serum OPG levels to arterial stiffness, carotid intima-media thickness (CIMT), and clinical and laboratory indices in RA patients. PATIENTS AND METHODS: Included in the study were 68 RA patients with no history or signs of CV disease and 48 healthy subjects Disease activity was assessed by the 28-joint disease activity score (DAS28) in RA patients. Serum OPG level was measured using enzyme-linked immunosorbent assay (ELISA). Carotid femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness and CIMT was evaluated by carotid ultrasonography. RESULTS: The mean serum OPG level was significantly higher in RA patients than controls (p < 0.001). Mean PWV and CIMT were also significantly increased in RA patients compared to controls (both p < 0.001). In RA patients, serum OPG level was significantly correlated with PWV and CIMT, as well as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody; but not with DAS28, high-sensitivity C-reactive protein (hsCRP), or erythrocyte sedimentation rate. CONCLUSION: Serum OPG levels were increased and correlated with CIMT and PWV in RA patients. In addition to PWV and CIMT, OPG may be a useful biomarker for CV risk management in RA patients. PMID- 26555552 TI - Disease activity, obesity, functional disability, and depression in patients with rheumatoid arthritis : Impact on lipid status, glycoregulation, and risk for coronary heart disease. AB - OBJECTIVES: This study aims to estimate the impact of disease activity, obesity, functional disability, and depression on lipid status, glycoregulation, and risk for coronary heart disease (CHD) in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 36 patients with RA (30 women and 6 men, mean age 54.9 years, mean disease duration 7.9 years) were included in this study. We estimated the impact of age, body mass index, disease activity [assessed by DAS28 index and C-reactive protein (CRP) value], functional ability (estimated using the HAQ disability index), and depression [assessed using the Beck Depression Inventory (BDI)] on glycoregulation, lipid status, and risk for CHD in our patients. Glycoregulation was assessed by measuring insulin resistance, insulin, and glucose in blood. Lipids tested in blood included total cholesterol, HDL and LDL cholesterol, and triglycerides (TG). The 10-year risk for CHD was estimated using the Framingham risk score. RESULTS: Of 36 patients, 11 (30.6 %) fulfilled the criteria for metabolic syndrome (MS). Ten of 11 patients (90.1 %) with MS have a 10-year risk for CHD greater than 10 % compared to only 3 of 25 patients (12 %) without MS (p = 0.0001). Patients with high disease activity had lower HDL values than patients with mild or moderate disease activity (1.4 vs. 1.7 mmol/l, p = 0.04). Significant correlations were observed between CRP level and insulinemia (rho = 0.57, p = 0.003), as well as CRP level and the HOMA index (rho = 0.59, p = 0.002). The body mass index (BMI) correlated significantly with total cholesterol (r = 0.46, p = 0.02), LDL (rho = 0.41, p = 0.04), and TG (rho = 0.65, p < 0.001) in blood. The HAQ-DI did not correlate either with parameters of glycoregulation or lipid status. There was a significant positive correlation between BDI and BMI (rho = 0.60, p < 0.001). CONCULSION: Active RA is independently associated with decreased HDL cholesterol and increased insulin resistance. Obesity was found to be an independent risk factor for increased total cholesterol, LDL cholesterol, and TG. Depressed patients with RA tend to be overweight or obese and, therefore, have an unfavorable lipid profile. PMID- 26555553 TI - Frequency and distribution of mixed Plasmodium falciparum-vivax infections in French Guiana between 2000 and 2008. AB - BACKGROUND: The two main plasmodial species in French Guiana are Plasmodium vivax and Plasmodium falciparum whose respective prevalence influences the frequency of mixed plasmodial infections. The accuracy of their diagnosis is influenced by the sensitivity of the method used, whereas neither microscopy nor rapid diagnostic tests allow a satisfactory evaluation of mixed plasmodial infections. METHODS: In the present study, the frequency of mixed infections in different part of French Guiana was determined using real time PCR, a sensitive and specific technique. RESULTS: From 400 cases of malaria initially diagnosed by microscopy, real time PCR showed that 10.75 % of the cases were mixed infections. Their prevalence varied considerably between geographical areas. The presence, in equivalent proportions, of the two plasmodial species in eastern French Guiana was associated with a much higher prevalence of mixed plasmodial infections than in western French Guiana, where the majority of the population was Duffy negative and thus resistant to vivax malaria. CONCLUSION: Clinicians must be more vigilant regarding mixed infections in co-endemic P. falciparum/P. vivax areas, in order to deliver optimal care for patients suffering from malaria. This may involve the use of rapid diagnostic tests capable of detecting mixed infections or low density single infections. This is important as French Guiana moves towards malaria elimination. PMID- 26555554 TI - Ethanol-Induced TLR4/NLRP3 Neuroinflammatory Response in Microglial Cells Promotes Leukocyte Infiltration Across the BBB. AB - We reported that the ethanol-induced innate immune response by activating TLR4 signaling triggers gliosis and neuroinflammation. Ethanol also activates other immune receptors, such as NOD-like-receptors, and specifically NLRP3-inflammasome in astroglial cells, to stimulate caspase-1 cleavage and IL-1beta and IL-18 cytokines production. Yet, whether microglia NLRs are also sensitive to the ethanol effects that contribute to neuroinflammation is uncertain. Using cerebral cortexes of the chronic alcohol-fed WT and TLR4(-/-) mice, we demonstrated that chronic ethanol treatment enhanced TLR4 mediated-NLRP3/Caspase-1 complex activation, and up-regulated pro-inflammatory cytokines and chemokines levels. Ethanol-induced NLRP3-inflammasome activation and mitochondria-ROS generation were also observed in cultured microglial cells. The up-regulation of CD45(high)/CD11b(+) cell populations and matrix metalloproteinase-9 levels was also noted in the cortexes of the ethanol-treated WT mice. Notably, elimination of the TLR4 function abolished most ethanol-induced neuroinflammatory effects. Thus, our results demonstrate that ethanol triggers TLR4-mediated NLRP3 inflammasome activation in glial cells, and suggest that microglia stimulation may compromise the permeability of blood-brain barrier events to contribute to ethanol-induced neuroinflammation and brain damage. PMID- 26555556 TI - Copper uptake by Pteris melanocaulon Fee from a Copper-Gold mine in Surigao del Norte, Philippines. AB - The ability of some plants to take up metal contaminants in the soil has been of increasing interest as an environmental approach to pollution clean-up. This study aimed to assess the ability of Pteris melanocaulon for copper(Cu) uptake by determining the Cu levels in the fern vis-a-vis surrounding soil and the location of Cu accumulation within its biomass. It also aimed to add information to existing literature as P. melanocaulon are found to be less documented compared to other fern metal accumulators, such as P. vittata. The P. melanocaulon found in the Suyoc Pit of a Copper-Gold mine in Placer, Surigao del Norte, Philippines exhibited a high Bioaccumulation Factor(BF) of 4.04 and a low Translocation Factor(TF) of 0.01, suggesting more Cu accumulation in the roots (4590.22 +/- 385.66 ug g(-1) Cu). Noteworthy was the Cu concentration in the rhizome which was also high (3539.44 +/- 1696.35 ug g(-1) Cu). SEM/EDX analyses of the Cu content in the roots indicated high elemental %Cu in the xylem (6.95%) than in the cortex (2.68%). The high Cu content in the roots and rhizomes and the localization of Cu in the xylem manifested a potential utilization of the fern as a metallophyte for rhizofiltration and phytostabilization. PMID- 26555555 TI - Long-term outcomes of ductal carcinoma in situ of the breast: a systematic review, meta-analysis and meta-regression analysis. AB - BACKGROUND: To summarize data on long-term ipsilateral local recurrence (LR) and breast cancer death rate (BCDR) for patients with ductal carcinoma in situ (DCIS) who received different treatments. METHODS: Systematic review and study-level meta-analysis of prospective (n = 5) and retrospective (n = 21) studies of patients with pure DCIS and with median or mean follow-up time of >=10 years. Meta-regression was performed to assess and adjust for effects of potential confounders - the average age of women, period of initial treatment, and of bias follow-up duration on recurrence- and death-rates in each treatment group. LR and BCDR rates by local treatment used were reported. Outside of randomized trials, remaining studies were likely to have tailored patient treatment according to the clinical situation. RESULTS: Nine thousand four hundred and four DCIS cases in 9391 patients with 10-year follow-up were included. The adjusted meta-regression LR rate for mastectomy was 2.6 % (95 % CI, 0.8-4.5); breast conserving surgery with radiotherapy (RT), 13.6 % (95 % CI, 9.8-17.4); breast conserving surgery without RT, 25.5 % (95 % CI, 18.1-32.9); and biopsy-only (residual predominately low-grade DCIS following inadequate excision), 27.8 % (95 % CI, 8.4-47.1). RT + tamoxifen (TAM) in conservation surgery (CS) patients resulted in lower LR compared to one or no adjuvant treatments: LR rate for CS + RT + TAM, 9.7 %; CS + RT(no TAM), 14.1 %; CS + TAM(no RT), 24.7 %; CS(alone), 25.1 % (linear trend for treatment P < 0.0001). Compared to CS + RT + TAM, a significantly higher invasive LR was observed for CS(alone), odds ratio (OR) 2.61 (P < 0.0001); CS + TAM(no RT), OR 2.52 (P = 0.001); CS + RT(no TAM), OR 1.59 (P = 0.022). BCDR was similar for mastectomy, breast-conserving surgery with or without RT (1.3-2.0 %) and non-significantly higher for biopsy-only (2.7 %). Additionally, the 15-year follow-up was reported where all like-studies had >= 15 year data sets; the biopsy-only patients had a meta-analysed total LR rate of 40.2 % and the invasive LR rate was 28.1 %. The biopsy-only patients had a >= 15 year BCDR (that included women with metastatic disease) of 17.9 %; the >= 15-year BCDR was 55.2 % for those with invasive LR. CONCLUSIONS: More local intervention was associated with greater local control for patients with DCIS at long-term follow-up. For patients undergoing breast-conservation, invasive LR was significantly lower when two rather than one adjuvant treatment modalities were given. PMID- 26555557 TI - TiO2 /Cu2 O Core/Ultrathin Shell Nanorods as Efficient and Stable Photocatalysts for Water Reduction. AB - P-type Cu2 O has been long considered as an attractive photocatalyst for photocatalytic water reduction, but few successful examples has been reported. Here, we report the synthesis of TiO2 (core)/Cu2 O (ultrathin film shell) nanorods by a redox reaction between Cu(2+) and in-situ generated Ti(3+) when Cu(2+) -exchanged H-titanate nanotubes are calcined in air. Owing to the strong TiO2 -Cu2 O interfacial interaction, TiO2 (core)/Cu2 O (ultrathin film shell) nanorods are highly active and stable in photocatalytic water reduction. The TiO2 core and Cu2 O ultrathin film shell respectively act as the photosensitizer and cocatalyst, and both the photoexcited electrons in the conduction band and the holes in the valence band of TiO2 respectively transfer to the conduction band and valence band of the Cu2 O ultrathin film shell. Our results unambiguously show that Cu2 O itself can act as the highly active and stable cocatalyst for photocatalytic water reduction. PMID- 26555558 TI - Respiratory Distress and Nephropathy in a Young Male With Small-Joint Polyarthritis. PMID- 26555559 TI - Incorporation of pharmacogenetic testing into medication therapy management. AB - AIM: To assess feasibility and patient satisfaction with a pharmacist-delivered medication therapy management (MTM) plus pharmacogenetic (PGx) testing service. METHODS: Thirty patients from a cardiology outpatient clinic were enrolled to attend two MTM sessions, undergo PGx testing and complete pre- and post intervention surveys. Outcome measures included duration of MTM sessions, clinical application of test results, self-reported medication adherence, patient recall of results and perceived value of testing and MTM. RESULTS: Overall, patients were very satisfied with the MTM plus PGx testing service. About half of participants (47%) were able to accurately recall their PGx test results. Comparable to MTM without PGx testing, the first MTM session averaged 40 min and the follow-up MTM session averaged 15 min. CONCLUSION: PGx testing incorporated into a clinical MTM service offered by pharmacists may be a feasible delivery model and is satisfactory to patients. PMID- 26555560 TI - Practices for Supporting and Confirming Decision-Making Involved in Kidney and Liver Donation by Related Living Donors in Japan: A Nationwide Survey. AB - This nationwide survey investigated the actual practices for supporting and confirming the decision-making involved in related living-organ donations in Japan, focusing on organ type and program size differences. Answers to a questionnaire survey were collected from 89 of the 126 (71%) kidney and 30 of the 35 (86%) liver transplantation programs in Japan that were involved in living donor transplantations in 2013. In 70% of the kidney and 90% of the liver transplantation programs, all donors underwent "third-party" interviews to confirm their voluntariness. The most common third parties were psychiatrists (90% and 83%, respectively). Many programs engaged in practices to support decision-making by donor candidates, including guaranteeing the right to withdraw consent to donate (70% and 100%, respectively) and prescribing a set "cooling-off period" (88% and 100%, respectively). Most donors were offered care by mental health specialists (86% and 93%, respectively). Third parties were designated by more of the larger kidney transplant programs compared with the smaller programs. In conclusion, the actual practices supporting and confirming the decision to donate a living organ varied depending on the organ concerned and the number of patients in the program. PMID- 26555561 TI - Recovery as an occupational journey: A scoping review exploring the links between occupational engagement and recovery for people with enduring mental health issues. AB - BACKGROUND/AIM: Mental health recovery can be defined in variety of different ways. First person accounts of people experiencing mental health issues and qualitative studies of recovery suggest engaging in personally meaningful and socially valued occupations is important during the process of recovering. This scoping review sought to explore how occupational engagement and recovery are interrelated. METHODS: Using Arksey and O'Malley's (2005) framework to guide the scoping review, searches of four electronic databases, manual citation tracking, and key authors' publications were conducted. Seventeen studies, published in the last 30 years, relevant to the topic were identified. Each was reviewed and data extracted to categorise the similarities and differences into themes. RESULTS: Most studies used qualitative, phenomenological and narrative research approaches. Findings across the studies indicate recovery is an ongoing occupational process that seems to involve experiences of gradual re-engagement, engaging within the stream of everyday occupational life, and full community participation. Engaging in meaningful and valued occupations appears to support recovering through fostering connectedness, hope, identity, meaning, and empowerment; establishing structured routines and assisting people in managing illness. CONCLUSION: This scoping review indicates occupational engagement is an important dimension of the recovery process: recovering is experienced through engaging in occupations, which, in turn, fosters personal recovery. Employment and volunteering have received most attention in studies of occupation and recovery. A broader view of the experiences and factors involved in the processes of 'occupational recovery' warrants further exploration to advance theory and inform recovery-oriented occupational therapy practice. PMID- 26555562 TI - Women in Academic Medicine: Measuring Stereotype Threat Among Junior Faculty. AB - BACKGROUND: Gender stereotypes in science impede supportive environments for women. Research suggests that women's perceptions of these environments are influenced by stereotype threat (ST): anxiety faced in situations where one may be evaluated using negative stereotypes. This study developed and tested ST metrics for first time use with junior faculty in academic medicine. METHODS: Under a 2012 National Institutes of Health Pathfinder Award, Stanford School of Medicine's Office of Diversity and Leadership, working with experienced clinicians, social scientists, and epidemiologists, developed and administered ST measures to a representative group of junior faculty. RESULTS: 174 School of Medicine junior faculty were recruited (62% women, 38% men; 75% assistant professors, 25% instructors; 50% white, 40% Asian, 10% underrepresented minority). Women reported greater susceptibility to ST than did men across all items including ST vulnerability (p < 0.001); rejection sensitivity (p = 0.001); gender identification (p < 0.001); perceptions of relative potential (p = 0.048); and, sense of belonging (p = 0.049). Results of career-related consequences of ST were more nuanced. Compared with men, women reported lower beliefs in advancement (p = 0.021); however, they had similar career interest and identification, felt just as connected to colleagues, and were equally likely to pursue careers outside academia (all p > 0.42). CONCLUSIONS: Innovative ST metrics can provide a more complete picture of academic medical center environments. While junior women faculty are susceptible to ST, they may not yet experience all of its consequences in their early careers. As such, ST metrics offer a tool for evaluating institutional initiatives to increase supportive environments for women in academic medicine. PMID- 26555563 TI - Consumer palatability scores, sensory descriptive attributes, and volatile compounds of grilled beef steaks from three USDA Quality Grades. AB - Consumer palatability scores, sensory descriptive attributes, and volatile compounds were assessed for beef Longissimus lumborum steaks of USDA Prime, Low Choice, and Standard grades. Overall and flavor liking was greater (P<0.05) for Prime and Low Choice. Initial flavor impact and fat-like attributes were greater (P<0.05) among Prime and Low Choice. Prime had greater (P<0.05) brown/roasted, beef identity, overall sweetness, and umami. Cardboard was greater (P<0.05) in Standard. Volatile compounds representing flavor development pathways were varied with quality grade. Standard had greater (P<0.05) abundances of n-aldehydes. Phenylacetaldehyde was greater (P<0.05) in Prime and Low Choice. Both 2,3 butanedione and 3-hydroxy-2-butanone were greatest (P<0.05) in Prime. Overall liking was positively correlated with many descriptive attributes, 3-hydroxy-2 butanone, and phenylacetaldehyde, and negatively correlated with cardboard, green, and n-aldehydes. While the measured attributes and volatiles may not be causative of flavor, this data indicates potential for prediction of flavor through their measurement. PMID- 26555564 TI - Genotyping and DNA microarray based characterization of Staphylococcus aureus isolates from rabbit carcasses. AB - Staphylococcus aureus can cause staphylococcal food poisoning. Although the organism is frequently detected on rabbit carcasses, little is known about the characteristics of S. aureus strains contaminating rabbit meat. In this study, 137 S. aureus isolates originating from 137 rabbit carcasses were spa typed and characterized by DNA microarray. The isolates were assigned to CC5, CC7, CC8, CC15, CC96, CC101, CC121, and ST890, and to 13 spa types (t056, t085, t091, t160, t179, t681, t741, t745, t1190, t1773, t4770, t8456, t14871). Enterotoxin genes detected included sea, sed, sej, and ser. In addition, the egc operon, encoding the newly described staphylococcal enterotoxins SEG/SEI/SElM/SElN/SElO/SElU, was found in all isolates except those of t091. While none of the examined isolates presented genes conferring methicillin, vancomycin, or aminoglycoside resistance, we frequently detected blaZ/I/R conferring resistance to penicillin. The isolates represented a heterogeneous group assigned to clonal lineages detected among humans and animals, with two spa types exclusively associated with rabbit meat (t4770, t8456). PMID- 26555565 TI - Assessment of the carotid artery intima-media complex through ultrasonography and the relationship with Pathobiological Determinants of Atherosclerosis in Youth. AB - OBJECTIVE: To evaluate the presence of carotid thickening and its relationship with the Pathobiological Determinants of Atherosclerosis in Youth score. METHODS: We carried out a cross-sectional study involving 512 brazilian adolescents. Variables such as sex, body mass index, concentrations of non-high-density lipoprotein and high-density lipoprotein cholesterol, blood pressure, blood glucose and glycated haemoglobin A1c levels that make up the score, and carotid thickening through the intima-media complex measured by ultrasound were evaluated. We adopted two cut-off points to evaluate carotid thickening, being considered altered for those higher or equal to the z-score 2+ and ?75th percentile. The association was assessed using the chi2 test and univariate and multivariate logistic regression analyses. RESULTS: High cardiovascular risk was present in 10.2% of the adolescents; carotid thickness was present in 4.3% determined by the z-score 2+ and in 25.0% determined by the 75th percentile. When measured by the z-score, carotid thickening was associated with high systolic blood pressure (p=0.024), high-non-high density lipoprotein cholesterol (p=0.039), and high cardiovascular risk assessed by the score and by the 75th percentile, with body mass index >30 (p=0.005). In the multivariate analysis, high cardiovascular risk was found to be independently associated with the presence of carotid thickness evaluated by the z-score, with risk four times greater (p=0.010) of presenting with this condition compared with individuals with low risk, and this fact was not observed when factors were analysed alone. CONCLUSION: The presence of high cardiovascular risk in adolescents assessed by the Pathobiological Determinants of Atherosclerosis in Youth score was associated with marked thickening of the carotid artery in healthy adolescents. PMID- 26555566 TI - Impact of recipient ACE I/D genotype on kidney function in renal transplant patients: a meta-analysis of cross-sectional and longitudinal studies. AB - AIM: To perform a systematic review and meta-analysis of studies evaluating the influence of recipient angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism on kidney function in renal transplant recipients. MATERIALS & METHODS: A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to December 2014. The methodological quality of identified studies was assessed using the MINORS criteria. RESULTS: A total of 15 studies evaluating the role of recipient ACE I/D were included in the meta analysis. In overall analyzes and subsequent subgroup and sensitivity analyzes, no evidence emerged of an effect of ACE I/D on serum creatinine levels, creatinine clearance or glomerular filtration rate. CONCLUSION: Although further investigation is still needed to determine the role of donor ACE genotype, recipient ACE I/D does not play a significant role on kidney function in renal transplant patients. PMID- 26555567 TI - Using Isolated Mitochondria from Minimal Quantities of Mouse Skeletal Muscle for High throughput Microplate Respiratory Measurements. AB - Skeletal muscle mitochondria play a specific role in many disease pathologies. As such, the measurement of oxygen consumption as an indicator of mitochondrial function in this tissue has become more prevalent. Although many technologies and assays exist that measure mitochondrial respiratory pathways in a variety of cells, tissue and species, there is currently a void in the literature in regards to the compilation of these assays using isolated mitochondria from mouse skeletal muscle for use in microplate based technologies. Importantly, the use of microplate based respirometric assays is growing among mitochondrial biologists as it allows for high throughput measurements using minimal quantities of isolated mitochondria. Therefore, a collection of microplate based respirometric assays were developed that are able to assess mechanistic changes/adaptations in oxygen consumption in a commonly used animal model. The methods presented herein provide step-by-step instructions to perform these assays with an optimal amount of mitochondrial protein and reagents, and high precision as evidenced by the minimal variance across the dynamic range of each assay. PMID- 26555568 TI - Highly sensitive detection of copper ions by densely grafting fluorescein inside polyethyleneimine core-silica shell nanoparticles. AB - In this work, polyethyleneimine (PEI) core-silica shell nanoparticles were synthesized and used for densely grafting fluorescent receptor units inside the core of these particles to result in multi-receptor units collectively sensing a target. Herein, copper ion quenching of the fluorescence intensity of a fluorescein isothiocyanate (FITC) system was selected as a model to confirm our proof-of-concept strategy. Our results showed that, compared to free FITC in solution, a 10-fold enhancement of the Stern-Volmer constant value for Cu(2+) quenching of the fluorescence intensity of the grafted state of FITC in PEI core silica shell nanoparticles was achieved. Furthermore, compared to a previous collective sensing scheme by densely grafting fluorescent receptor units on a silica nanoparticle surface, the proposed scheme, which grafted fluorescent receptor units inside a polymer nano-core, was simple, highly efficient and presented higher sensitivity. PMID- 26555570 TI - Correction: Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers. PMID- 26555569 TI - Family physicians' intention to support women in making informed decisions about breast cancer screening with mammography: a cross-sectional survey. AB - BACKGROUND: The net benefits of routine breast cancer screening with mammography have been questioned, and there is evidence to indicate that supporting women to make an informed decision about breast cancer screening with mammography is preferable. The aims of this study were to assess the intention of family physicians to provide women with this support and the determinants of this intention, and to identify factors that might influence family physicians adopting this behavior. METHODS: Family physicians from the province of Quebec, Canada, attending a 45-min lecture on informed decision making and cancer screening were asked to complete a questionnaire after the lecture regarding their intention to adopt the behavior. The questions, based on the Theory of Planned Behavior, measured physicians' intention and its determinants (attitude, perceived behavioral control, and socio-professional norm) regarding supporting women to make informed decisions about breast cancer screening with mammography. Open-ended questions were also used to explore complementary factors influencing their intention. RESULTS: Out of 800 questionnaires distributed, 301 (38 %) were returned and 288 were included in data analysis. The mean +/- standard deviation and median score for intention were respectively 1.9 +/- 1.2 and 2.0 on a 6-point Likert scale (-3 to +3). Perceived behavioral control was the variable most strongly associated with intention (high versus low score, odds ratio = 15.7, 95 % CI 6.7-36.6), followed by attitude (high versus low score, odds ratio = 7.5, 95 % CI 3.3-16.8), then social norm (high versus low score, odds ratio = 5.8, 95 % CI 2.6-12.9). The most-reported barrier to adopting the behavior was time constraints (41 %) while the most-reported facilitator was availability of relevant decision support tools (29 %). CONCLUSIONS: Respondents showed strong intention to support women in informed decision-making about breast cancer screening, the strongest predictor being perceived behavioral control. These results could contribute to training physicians to integrate this behavior into their practices and to designing relevant decision support tools. PMID- 26555571 TI - Validation of administrative data case definitions for gestational diabetes mellitus. AB - AIM: To examine, using administrative data, the validity of two algorithms for identifying gestational diabetes mellitus: 1) the current National Diabetes Surveillance System algorithm for excluding gestational diabetes cases and 2) gestational diabetes-specific ICD codes in the delivery-related hospitalization. METHODS: This was a retrospective study of all women, aged 18-54 years, residing in Alberta, Canada, with singleton deliveries between 1 April 1999 and 31 March 2010. We linked Alberta Perinatal Health Program data on all deliveries to administrative claims data from Alberta Health using the mother's personal health number. For both gestational diabetes algorithms, we calculated the sensitivity, specificity, positive predictive value, negative predictive value and agreement, using gestational diabetes identified in the Alberta Perinatal Health Program as the 'gold standard'. RESULTS: Our study sample consisted of 411 390 deliveries for 273 152 women. The mean (sd) age was 29.1 (5.6) years and 82.3% of the women were white. Crude rates of gestational diabetes were 3.9% (16 215 cases), 1.3% (5189 cases) and 4.0% (16 440 cases) according to the Alberta Perinatal Health Program, National Diabetes Surveillance System and ICD code-based algorithms, respectively. Compared with the Alberta Perinatal Health Program database, the National Diabetes Surveillance System algorithm had a sensitivity of 25% and specificity of 100%, whereas the gestational diabetes-specific ICD code-based algorithm had a sensitivity of 86% and specificity of 99%. CONCLUSIONS: The National Diabetes Surveillance System algorithm underestimates the number of gestational diabetes cases. A more valid mechanism to identify gestational diabetes prevalence using health administrative data is the use of gestational diabetes-specific ICD-9/10 codes in the delivery hospitalization. PMID- 26555572 TI - Cerebrospinal Fluid Abeta42 Levels: When Physiological Become Pathological State. AB - Impaired amyloid beta (Abeta) metabolism is currently considered central to understand the pathophysiology of Alzheimer's disease (AD). Measurements of cerebrospinal fluid Abeta levels remain the most useful marker for diagnostic purposes and to individuate people at risk for AD. Despite recent advances criticized the direct role in neurodegeneration of cortical neurons, Abeta is considered responsible for synaptopathy and impairment of neurotransmission and therefore remains the major trigger of AD and future pharmacological treatment remain Abeta oriented. However, experimental and clinical findings showed that Abeta peptides could have a wider range of action responsible for cell dysfunction and for appearance of clinico-pathological entities different from AD. Such findings may induce misunderstanding of the real role played by Abeta in AD and therefore strengthen criticism on its centrality and need for CSF measurements. Aim of this review is to discuss the role of CSF Abeta levels in light of experimental, clinical pathologic, and electrophysiological results in AD and other pathological entities to put in a correct frame the value of Abeta changes. PMID- 26555573 TI - Chiroptical Probing of Lanthanide-Directed Self-Assembly Formation Using btp Ligands Formed in One-Pot Diazo-Transfer/Deprotection Click Reaction from Chiral Amines. AB - A series of enantiomeric 2,6-bis(1,2,3-triazol-4-yl)pyridines (btp)-containing ligands was synthesized by a one-pot two-step copper-catalyzed amine/alkyne click reaction. The Eu(III) - and Tb(III) -directed self-assembly formation of these ligands was studied in CH3 CN by monitoring their various photophysical properties, including their emerging circular dichroism and circularly polarized luminescence. The global analysis of the former enabled the determination of both the stoichiometry and the stability constants of the various chiral supramolecular species in solution. PMID- 26555574 TI - Environmentally Robust Rhodamine Reporters for Probe-based Cellular Detection of the Cancer-linked Oxidoreductase hNQO1. AB - We successfully synthesized a fluorescent probe capable of detecting the cancer associated NAD(P)H: quinoneoxidoreductase isozyme-1 within human cells, based on results from an investigation of the stability of various rhodamines and seminaphthorhodamines toward the biological reductant NADH, present at ~100-200 MUM within cells. While rhodamines are generally known for their chemical stability, we observe that NADH causes significant and sometimes rapid modification of numerous rhodamine analogues, including those oftentimes used in imaging applications. Results from mechanistic studies lead us to rule out a radical-based reduction pathway, suggesting rhodamine reduction by NADH proceeds by a hydride transfer process to yield the reduced leuco form of the rhodamine and oxidized NAD(+). A relationship between the structural features of the rhodamines and their reactivity with NADH is observed. Rhodamines with increased alkylation on the N3- and N6-nitrogens, as well as the xanthene core, react the least with NADH; whereas, nonalkylated variants or analogues with electron withdrawing substituents have the fastest rates of reaction. These outcomes allowed us to judiciously construct a seminaphthorhodamine-based, turn-on fluorescent probe that is capable of selectively detecting the cancer-associated, NADH-dependent enzyme NAD(P)H: quinoneoxidoreductase isozyme-1 in human cancer cells, without the issue of NADH-induced deactivation of the seminaphthorhodamine reporter. PMID- 26555575 TI - Previous gestational diabetes history is associated with impaired coronary flow reserve. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a prediabetic state that is known to increase the risk of cardiovascular diseases. We have investigated coronary flow velocity reserve (CFVR) and epicardial fat thickness (EFT), and left ventricular diastolic function in patients with a history of previous GDM (p GDM). METHODS: Ninety-three women with GDM history and 95 healthy women without GDM history were recruited. We used transthoracic Doppler echocardiography to assess CFVR, EFT, and left ventricular diastolic function. Insulin resistance of each subject was assessed with homeostasis model assessment insulin resistance (HOMA-IR). Hemoglobin A1c and high-sensitivity C-reactive protein (hsCRP) were also measured in all patients. RESULTS: CFVR values were significantly lower (2.34 +/- 0.39 versus 2.80 +/- 0.24, p < 0.001) and EFT values were significantly higher in patients with p-GDM than the control group (5.5 +/- 1.3 versus 4.3 +/- 1.1, p < 0.001). E/E' ratio (7.21 +/- 1.77 versus 6.53 +/- 1.38, p = 0.003), hemoglobin A1c (5.2 +/- 0.4 and 5.0 +/- 0.3, p = 0.001), HOMA-IR (2.8 +/- 1.4 versus 1.7 +/- 0.9, p = 0.04), and hsCRP levels were significantly higher in the p-GDM group than the control group. Multivariate analysis revealed that gestational diabetes history is independently associated with CFVR. CONCLUSION: Women with a GDM history may be at more risk regarding coronary microvascular dysfunction compared to the healthy ones. PMID- 26555576 TI - Minimum ovarian stimulation involving combined clomiphene citrate and estradiol treatment for in vitro fertilization of Bologna-criteria poor ovarian responders. AB - AIM: The aim of this study was to assess the efficacy of a minimal ovarian stimulation involving combined clomiphene citrate (CC) and estradiol (E2) administration for poor responders with diminished ovarian reserve (DOR). MATERIAL AND METHODS: In this case-control study, we recruited 41 consecutive hypergonadotropic poor responders (69 cycles) who met Bologna-criteria and had experienced cancellation of oocyte retrieval. In 10 (20 cycles), 11 (21 cycles) and 20 patients (28 cycles) between 2012 and 2014, follicular development was induced using an E2 cycle, CC cycle and CC + E2 cycle, respectively. After confirmation of high follicle-stimulating hormone levels (15-40 mIU/ml) at menstrual day 3, DOR patients were treated with oral E2 of 1.0 mg/day, CC of 100 mg/day, or both CC and E2 continuously, until ovulation induction. Two days later, we transvaginally aspirated the follicles, performed in vitro fertilization, and cryopreserved the cleavage embryos. One warmed embryo was transferred into the uterus during the hormone replacement cycles. RESULTS: For the E2, CC, and CC + E2 cycles, the median patient age was 41 years in all groups, and the serum anti-Mullerian hormone levels were 0.2 +/- 0.3, 0.4 +/- 0.4, and 0.2 +/- 0.3 ng/mL, respectively (P = 0.258); follicular development failure rates were 50.0%, 19.0%, and 3.6%, respectively (P < 0.001); numbers of retrieved oocytes (/cycle) were 0.5 +/- 0.6, 0.8 +/- 0.7, and 1.2 +/- 1.1, respectively (P = 0.033); and clinical pregnancy rates (/cycle) were 5.0%, 4.8%, and 10.7%, respectively (P = 0.725). CONCLUSION: CC + E2 administration for the patients with DOR was effective with a lower cancellation rate of oocyte retrieval and a higher number of retrieved oocytes. PMID- 26555577 TI - Zn-Mediated Reduction of Oxalyl Chloride Forming CO and Its Application in Carbonylation Reactions. AB - An efficient protocol for the generation of carbon monoxide by Zn-mediated reduction of oxalyl chloride has been developed. Oxalyl chloride was applied as an extremely effective substitute for toxic gaseous CO in the palladium-catalyzed alkoxy-/amino-/hydrogen-/hydroxycarbonylation processes providing industrially interesting esters, amides, aldehydes, and carboxylic acids in good to excellent yields. This new procedure can be applied to various carbonylation reactions in the presence of a transition metal catalyst under mild conditions and with a stoichiometric amount of CO source. PMID- 26555578 TI - Whole Exome Sequencing of Rapid Autopsy Tumors and Xenograft Models Reveals Possible Driver Mutations Underlying Tumor Progression. AB - Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy due to its propensity to invade and rapidly metastasize and remains very difficult to manage clinically. One major hindrance towards a better understanding of PDAC is the lack of molecular data sets and models representative of end stage disease. Moreover, it remains unclear how molecularly similar patient-derived xenograft (PDX) models are to the primary tumor from which they were derived. To identify potential molecular drivers in metastatic pancreatic cancer progression, we obtained matched primary tumor, metastases and normal (peripheral blood) samples under a rapid autopsy program and performed whole exome sequencing (WES) on tumor as well as normal samples. PDX models were also generated, sequenced and compared to tumors. Across the matched data sets generated for three patients, there were on average approximately 160 single-nucleotide mutations in each sample. The majority of mutations in each patient were shared among the primary and metastatic samples and, importantly, were largely retained in the xenograft models. Based on the mutation prevalence in the primary and metastatic sites, we proposed possible clonal evolution patterns marked by functional mutations affecting cancer genes such as KRAS, TP53 and SMAD4 that may play an important role in tumor initiation, progression and metastasis. These results add to our understanding of pancreatic tumor biology, and demonstrate that PDX models derived from advanced or end-stage likely closely approximate the genetics of the disease in the clinic and thus represent a biologically and clinically relevant pre-clinical platform that may enable the development of effective targeted therapies for PDAC. PMID- 26555579 TI - Corneal Indocyanine Green Angiography to Guide Medical and Surgical Management of Corneal Neovascularization. AB - PURPOSE: To illustrate the role of corneal angiography in the clinical assessment and surgical treatment of patients with complex corneal neovascularization (CoNV). METHODS: A case series of 3 patients with CoNV is presented whose management was guided by indocyanine green (ICG) and fluorescein corneal angiography. In the first case, there was recurrent lipid exudation into an intrastromal cleft from CoNV; in the second, there was progressive exudation from CoNV at the graft-host interface; in the third, CoNV was associated with rejection after deep anterior lamellar keratoplasty. RESULTS: In the first case, angiography helped to identify and treat the feeder vessels and stop further leakage. In the second case, it was possible using angiography to differentiate CoNV arising from iris and limbal vasculature enabling angiographic-guided fine needle diathermy with cessation of exudation. In the third case, angiography revealed the location of CoNV in the host-graft interface after deep anterior lamellar keratoplasty, rather than within the corneal stroma. CONCLUSIONS: Corneal angiography is a useful diagnostic tool to guide medical and surgical management of CoNV by enabling the localization of vessel depth and topography. PMID- 26555581 TI - Cytokine Dosage in Fresh and Preserved Human Amniotic Membrane. AB - PURPOSE: To evaluate cytokine concentrations in amniotic membrane (AM) preserved in different preservation media, temperatures, and times and to compare them with those in fresh AM. METHODS: Placentas were harvested from 8 women undergoing cesarean delivery, with each then divided into 17 pieces for the following preservation methods: at 2 different temperatures (-80 and 0 degrees C), in 2 different preservation media (dimethyl sulfoxide and enriched TC199; Ophthalmos), and for different time periods (for 1, 7, 60, and 180 days). Nonpreserved fresh AM was used as a control. An enzyme-linked immunosorbent assay was performed on the supernatant for detection of the following cytokines: epidermal growth factor, basic fibroblast growth factor, hepatocyte growth factor, keratinocyte growth factor, transforming growth factor-beta, and interleukins 4 and 10, and the findings were assessed by post hoc analysis of variance. RESULTS: AM preserved at -80 degrees C showed less decrease in the concentration of 4 cytokines. Three cytokines showed less decrease in AM preserved in the TC199 medium, whereas 1 showed less decrease in AM preserved in dimethyl sulfoxide. After storage, 5 cytokine concentrations remained stable for up to 1 day, 3 remained stable for up to 7 days, and all showed significant loss thereafter. CONCLUSIONS: The AM storage temperature of -80 degrees C was found optimal for maintaining the concentrations of most of the tested cytokines, and enriched TC199 medium was the optimal long-term storage medium for maintaining the concentration of 3 of the cytokines, and with less decrease. When possible, AM should be used within 1 to 7 days after harvesting. PMID- 26555580 TI - Confocal Microscopic Analysis of a Rabbit Eye Model of High-Incidence Recurrent Herpes Stromal Keratitis. AB - PURPOSE: Using CJLAT, a chimeric herpes simplex virus (HSV-1) that produces a high incidence of herpes stromal keratitis (HSK) in latently infected rabbits, and in vivo confocal microscopy (CM), we characterized the cellular events that precede the development of HSK. METHODS: Thirty days after infection, in vivo CM was performed daily for 10 days and then weekly for up to 80 days after infection. RESULTS: We detected 3 types of subclinical corneal lesions before HSK was clinically apparent: (1) small epithelial erosions; (2) regenerating epithelium overlying small cell infiltrates within the basal epithelial cell layer; and (3) dendritic-like cells within the basal epithelial layer overlying stromal foci containing infiltrating cells. Sequential in vivo CM observations suggested that subclinical foci resolved over time but were larger and more abundant with CJLAT than with wild-type HSV-1 McKrae. Active HSK was observed only with CJLAT and was initially associated with a large epithelial lesion overlying stromal immune cell infiltrates. CONCLUSIONS: These results suggest that replication in the cornea of reactivated virus from the trigeminal ganglia produces epithelial lesions, which recruit immune cell infiltrates into the basal epithelial layer and anterior stroma. The virus is usually cleared rapidly eliminating viral antigens before the arrival of the immune cells, which disperse. However, if the virus is not cleared rapidly, or if an additional reactivation results in an additional round of virus at the same site before the immune cells disperse, then the immune cells are stimulated and may induce an immunopathological response leading to the development of HSK. PMID- 26555582 TI - Immediate Postoperative Intraocular Pressure Changes After Anterior Chamber Air Fill in Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To monitor the intraocular pressure (IOP) changes immediately after anterior chamber air tamponade in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Twenty-four patients undergoing DMEK and 16 patients undergoing rebubbling after DMEK were enrolled (n = 40). All DMEK patients had inferior iridectomy and nearly full intracameral air tamponade with an aimed IOP of 25 mm Hg at the end of surgery. The IOP was measured at 1, 2, 3, 5, 12, 24 hours and 1 week postoperatively. RESULTS: After anterior chamber air fill in DMEK, the IOP increased from preoperative baseline, 12.1 +/- 2.9 mm Hg, to 26.3 +/- 4.7 mm Hg, P < 0.001. Mean IOP was significantly elevated in the first 2 hours, 19.4 +/- 10.5 mm Hg and 17.0 +/- 7.4 mm Hg, P = 0.007 and 0.006, respectively. Then, it lowered to the baseline level, 14.0 +/- 4.7 mm Hg, P > 0.05, and remained stable during follow-ups. An asymptomatic IOP elevation above 30 mm Hg was detected in 3 patients (12.5%) within the first 2 hours. None had preexisting glaucoma. Most episodes could be controlled by antiglaucoma medications and upright positioning. The pattern of IOP changes after rebubbling was similar to that after DMEK but the IOP dropped sharply to the baseline level after 1 hour and had no incidence of IOP elevations beyond 30 mm Hg. CONCLUSIONS: Adequate inferior iridectomy greatly alleviates the risk and severity of acute IOP rises after nearly full anterior chamber air tamponade in DMEK. Standard IOP adjustment at the end of DMEK surgery with postoperative IOP monitoring especially in the first 2 postoperative hours is advisable when there is no postoperative default air release. PMID- 26555583 TI - Single-Pass Microkeratome System for Eye Bank DSAEK Tissue Preparation: Is Stromal Bed Thickness Predictable and Reproducible? AB - PURPOSE: To evaluate the predictability and reproducibility of stromal bed thickness for single-pass donor Descemet stripping automated endothelial keratoplasty (DSAEK) tissue preparation, using the ML7 Microkeratome Donor Cornea System (Med-logics Inc, Athens, TX). METHODS: In this retrospective chart review of 256 consecutive corneal tissue preparations for DSAEK surgery, from June 2013 to August 2014, tissue thicknesses were divided into 3 groups, depending on surgeon preference: <91 MUm (group A), 90 to 120 MUm (group B), and 120 to 160 MUm (group C). Precut and postcut data were recorded. RESULTS: Average postcut donor corneal thickness was 114 +/- 30 MUm (range 60-183 MUm), whereas the average in group A was 97 +/- 23 MUm (range 60-128), in group B was 113 +/- 21 MUm (range 77-179), and in group C was 134 +/- 43 (range 89-183). Average postcut endothelial cell density was very adequate at 3013 +/- 250 cells per square millimeter. There were a total of 7 failed procedures from 256 attempts, which represents a rate of 2.7%. This rate decreases to 1.5% when analyzing the last 200 cuts. CONCLUSIONS: The ML7 Microkeratome Donor Cornea System allows for reliable and reproducible DSAEK tissue preparation. Ultrathin DSAEK tissues can be prepared with a single-pass. Aiming for a graft thickness between 90 and 120 MUm seems to be most reliable. PMID- 26555584 TI - Changes in Corneal Biomechanical Properties After Descemet Stripping Automated Endothelial Keratoplasty for Pseudophakic Bullous Keratopathy. AB - PURPOSE: To compare corneal biomechanical properties and intraocular pressure (IOP) in eyes with pseudophakic bullous keratopathy (PBK) before and after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This prospective nonrandomized intrasubject comparative study was conducted on 44 eyes of 22 patients with the diagnosis of PBK who underwent DSAEK in one eye. IOP was measured by Goldmann applanation tonometer, and central corneal thickness was measured by ultrasound pachymetry. The ocular response analyzer was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann related IOP, and cornea-compensated IOP. The same measurements were performed in the normal fellow eyes which served as controls. All measurements were performed preoperatively and 6 months postoperatively. RESULTS: The mean patient age was 67 +/- 14 years. Mean preoperative CH and CRF values in the DSAEK group were 5.77 +/ 2.94 and 6.39 +/- 2.72 mm Hg, respectively, which were significantly lower than those measured in the control group (8.2 +/- 2.47 and 8.43 +/- 2.49 mm Hg, respectively, P = 0.001 for both comparisons). Postoperatively, CH and CRF demonstrated a significant increase (7.09 +/- 3.68 mm Hg, P = 0.05 and 8.21 +/- 3.84 mm Hg, P = 0.03, respectively) in operated eyes approaching the normal values measured in the control eyes. CONCLUSIONS: Corneal biomechanical parameters were significantly lower in PBK eyes than in the normal fellow eyes. These metrics significantly increased after DSAEK and reached values measured in the normal fellow eyes. PMID- 26555585 TI - Treatment Modalities and Clinical Outcomes in Ocular Sequelae of Stevens-Johnson Syndrome Over 25 Years--A Paradigm Shift. AB - PURPOSE: To highlight and compare the outcomes of management for the ocular sequelae of Stevens-Johnson syndrome (SJS) over 25 years in a tertiary eye care institute. METHODS: A retrospective chart review of 798 eyes of 399 patients with SJS evaluated between January 1990 and December 2004 (group I) and of 847 eyes of 517 patients between January 2005 and December 2014 (group II) was done. The primary and secondary outcome measures were a change in the best-corrected visual acuity (BCVA) and an improvement in the symptoms and the ocular surface status, respectively. The groups were subdivided into procedures for ocular surface stabilization (A) and visual rehabilitation (B) and those managed conservatively (C). RESULTS: In the subgroup A of group II, an improvement/stabilization of BCVA after punctal cautery (231 eyes), mucous membrane grafting for lid margin keratinization (393 eyes), and fornix reconstruction (28 eyes) was noted in 93.6% of eyes. In subgroup B, all 10 eyes that underwent limbal allograft in group I failed when compared with an improvement of BCVA to better than 20/200 in 65.5% of the 61 eyes that underwent keratoprostheses. It was noted that the limbal status worsened in 66.9% of eyes treated conservatively in group I. CONCLUSIONS: Stabilization procedures show a beneficial role while conservative management can lead to deterioration in chronic ocular sequelae of SJS. Keratoprosthesis, specifically the modified osteo-odonto-keratoprosthesis, forms the mainstay for visual rehabilitation in the end-stage disease. This study highlights the improved outcomes with a paradigm shift in the management modalities. PMID- 26555586 TI - Corneal Diameter as a Factor Influencing Corneal Astigmatism After Cataract Surgery. AB - PURPOSE: To evaluate the corneal horizontal diameter [white-to-white (WTW) distance] as a factor influencing surgically induced astigmatism (SIA) and postoperative astigmatism. METHODS: A total of 330 eyes with corneal astigmatism <=1.5 D underwent cataract surgery with phacoemulsification. A 3-step, superotemporal for the right eye and superonasal for the left eye, clear corneal incision of 3.0 mm was made. Four groups were created according to WTW distance: group A <=11.6 mm, group B 11.7 to 11.9 mm, group C 12.0 to 12.2 mm, and group D >=12.3 mm. SIA was calculated by vector analysis using the Alpins method. We noted all cases, in which a change greater than 0.5 diopters (D) in astigmatism took place and a change greater than 20 degrees in axis torque, despite axis direction, on the first and sixth postoperative months. RESULTS: SIA was found in group A 0.98 D +/- 0.6 (SD), B 0.79 D +/- 0.43 (SD), C 0.68 D +/- 0.45 (SD), and D 0.53 D +/- 0.32 (SD) at the first postoperative month. At the sixth postoperative month, SIA was 0.77 D +/- 0.43 (SD), 0.69 D +/- 0.34 (SD), 0.62 +/- 0.36 (SD), and 0.49 D +/- 0.27 (SD), respectively. A change greater than 0.5 D in corneal astigmatic power at the first and sixth months postoperatively was significantly lower in eyes with WTW distance 12.0 to 12.2 mm and >=12.3 mm in comparison with eyes with WTW distance <=11.6 mm and 11.7 to 11.9 mm (P < 0.05). Changes greater than 20 degrees in astigmatic axis at the first and sixth postoperative months were not significantly different according to the horizontal corneal diameter. CONCLUSIONS: WTW distance should always be measured preoperatively when planning cataract surgery and should be accounted for in cases of large and small corneas. PMID- 26555587 TI - Potency and Sterility of Fortified Tobramycin, Fortified Vancomycin, and Moxifloxacin at 4, 24, and 35 degrees C for 14 Days. AB - PURPOSE: To assess the potency and sterility of ophthalmic antibiotic drops commonly used in the treatment of bacterial keratitis. METHODS: This was a basic investigation. Three drugs were tested: fortified vancomycin 25 mg/mL, fortified tobramycin 14 mg/mL, and moxifloxacin 5 mg/mL. A bottle of each was stored separately at 4, 24, and 35 degrees C, with the potency determined by microbiological assay at 0, 7, and 14 days. Differences in potency were assessed by 2-way analysis of variance followed by a 1-way repeated-measures analysis of variance with Bonferroni post hoc testing as warranted. Sterility of drugs when handled by patients for varying periods was confirmed by culturing samples on MacConkey and sheep blood agars. RESULTS: The concentration of fortified tobramycin and moxifloxacin remained constant over 14 days at the 3 tested temperatures. The concentration of fortified vancomycin remained constant at 4 degrees C, but it declined by 38% +/- 1% (P = 0.001) at 24 degrees C on day 14 and by 48% +/- 1% (P = 0.001) and 78% +/- 3% (P = 0.0009) at 35 degrees C on days 7 and 14, respectively. A total of 49 drops (mean, 7.3 days; range, 1-18 days) were tested for sterility, and all were negative for microbial contamination. CONCLUSIONS: All 3 drugs remained potent at 4 degrees C for up to 14 days. Fortified tobramycin and moxifloxacin also maintained potency for 14 days at 24 and 35 degrees C. In contrast, fortified vancomycin lost its potency by day 14 at 24 degrees C and by day 7 at 35 degrees C. All in-use antibiotic drops tested were sterile. The results indicate that patients should be cautioned to store vancomycin under refrigerator or at least under cool conditions. PMID- 26555588 TI - Nitrogen Mustard-Induced Corneal Injury Involves DNA Damage and Pathways Related to Inflammation, Epithelial-Stromal Separation, and Neovascularization. AB - PURPOSE: To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to the vesicating agent, nitrogen mustard (NM), a bifunctional alkylating analog of the chemical warfare agent sulfur mustard. METHODS: Toxic effects and associated mechanisms were examined in maximally affected corneal tissue using corneal cultures and human corneal epithelial (HCE) cells exposed to NM. RESULTS: Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation, and levels of vascular endothelial growth factor, cyclooxygenase 2, and matrix metalloproteinase-9. In HCE cells, NM exposure resulted in a dose-dependent decrease in cell viability and proliferation, which was associated with DNA damage in terms of an increase in p53 ser15, total p53, and H2A.X ser139 levels. NM exposure also induced caspase-3 and poly ADP ribose polymerase cleavage, suggesting their involvement in NM-induced apoptotic death in the rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in cyclooxygenase 2, matrix metalloproteinase-9, and vascular endothelial growth factor levels in HCE cells, indicating a role of these molecules and related pathways in NM-induced corneal inflammation, epithelial-stromal separation, and neovascularization. NM exposure also induced activation of activator protein 1 transcription factor proteins and upstream signaling pathways including mitogen activated protein kinases and Akt protein kinase, suggesting that these could be key factors involved in NM-induced corneal injury. CONCLUSIONS: Results from this study provide insight into the molecular targets and pathways that could be involved in NM-induced corneal injuries laying the background for further investigation of these pathways in vesicant-induced ocular injuries, which could be helpful in the development of targeted therapies. PMID- 26555589 TI - Formation of Segmental Rounded Nodules During Infiltration of Adult T-Cell Leukemia Cells Into the Ocular Mucous Membrane. AB - PURPOSE: To document a case of adult T-cell leukemia (ATL) cell infiltration into the ocular mucous membrane that presented with rounded nodule formation. METHODS: Observational case report. RESULTS: A 36-year-old woman presented with bilateral conjunctival hyperemia and small papules on the legs and face. After complaining of significant fatigue at 6 months, she was diagnosed with high-risk chronic-type ATL. Ophthalmic examination revealed the formation of bilateral segmental rounded nodules, which were located both at the bulbar conjunctiva around the corneal limbus and at the palpebral conjunctiva around each lacrimal punctum. Although cellular infiltrations were also seen at the corneal subepithelium and stroma, no cellular infiltrations were observed in the anterior chamber, vitreous, or retina. Biopsy was performed of the bulbar and palpebral conjunctiva, and the polymerase chain reaction detected HTLV-1 proviral DNA and monoclonal T-cell receptor gamma-chain gene rearrangement in both samples. Pathological evaluations identified atypical lymphoid cells that were consistent with ATL cells. These analyses confirmed that the rounded nodules were formed in conjunction with the infiltration of ATL cells. CONCLUSIONS: The formation of multiple rounded nodules during ATL cell infiltration into the ocular mucous membrane, especially at the palpebral conjunctiva around the lacrimal punctum, may be a distinguishing feature of ATL. PMID- 26555590 TI - Safety of Intracameral Injection of Minimal Bactericidal Concentration of Povidone Iodine on the Corneal Endothelium in a Rabbit Model. AB - PURPOSE: To investigate the safety of intracameral injection of minimum bactericidal concentration (MBC) of povidone iodine (PI) on the corneal endothelium in a rabbit model as a proposed method of prophylaxis against postoperative endophthalmitis. METHODS: We included 32 New Zealand white rabbits in the study. Twenty-four rabbits received intracameral injections of 0.1 mL of 0.25% PI, and they were sequentially killed at intervals; first, seventh, and 14th day. The control group included 4 rabbits that received intracameral injections of 0.1 mL normal saline, and 4 rabbits that underwent the same intraocular procedure without injections (sham operated). Slit-lamp examination and ultrasonic corneal pachymetry were performed before and after injections for both eyes. The corneas were histopathologically examined by light and electron microscopy. RESULTS: MBC of PI (0.25%) was toxic to rabbits' corneal endothelium as evident by histopathological changes, corneal edema, and increased corneal thickness on day 1. Signs of healing were obvious on day 7 and were almost complete on day 14, as detected by histopathology, subsidence of corneal edema, and normalization of corneal thickness. CONCLUSIONS: MBC (0.25%) of PI was found toxic to the rabbits' corneal endothelium, with progressive regeneration and complete healing within 2 weeks. To our knowledge, we are the first to use MBC of PI in intracameral injection trials. Further studies on primates, which have more comparable regenerative capacity to humans' corneal endothelium, are encouraged to evaluate their endothelial healing response. PMID- 26555591 TI - Long-Term Results of Phototherapeutic Keratectomy Versus Mechanical Epithelial Removal Followed by Corneal Collagen Cross-Linking for Keratoconus. AB - PURPOSE: To compare the long-term visual outcomes of patients with keratoconus treated with either phototherapeutic keratectomy (PTK) or mechanical epithelial removal before corneal collagen cross-linking (CXL) at 1, 3, 6, and 12 months postoperatively. METHODS: CXL was performed by 1 of 3 surgeons (K.B., W.B.J., or G.M.). Seventeen eyes underwent mechanical epithelial removal before CXL and were consecutively selected after being matched with the 17 eyes in the PTK group for the variables of procedure date, average keratometry, and pachymetry. All cones were central. Manifest refraction spherical equivalent, sphere, cylinder, corrected distance visual acuity (CDVA), and pachymetry were measured and compared preoperatively and in follow-up. RESULTS: The mean CDVA change in the PTK group at 12 months postoperatively was statistically different from the mean CDVA change in the mechanical group at 12 months postoperatively (P = 0.031). The PTK group had significantly better outcomes in visual acuity 12 months postoperatively than did the mechanical group (P > 0.05). The mean number of lines of improvement in the PTK and mechanical groups were 2.30 +/- 0.96 and 0.00 +/- 0.33 lines, respectively (P = 0.0036). The mean change between the preoperative and 12 months postoperative manifest refraction spherical equivalent for the PTK and mechanical groups were 0.78 +/- 0.65 and 0.17 +/- 0.65, respectively (P > 0.05). CONCLUSIONS: PTK CXL resulted in better visual outcomes in comparison with mechanical epithelial removal CXL 1 year after treatment. PMID- 26555592 TI - Single-Pass Dissection of Ultrathin Organ-Cultured Endothelial Lamellae Using an Innovative Microkeratome System. AB - PURPOSE: To determine the feasibility, dissection accuracy, and endothelial viability of ultrathin endothelial lamellae harvested from organ-cultured corneas using a single-pass with an innovative motor-driven linear microkeratome system. METHODS: Forty-eight (n = 48) paired organ-cultured human corneas were randomly assigned to dissection (study eyes, n = 24) with fellow eyes serving as the control (fellow eyes, n = 24). After organ culture and deswelling in a medium containing 6% dextran, endothelial lamellae with a target thickness <=100 MUm were dissected using a motor-driven linear microkeratome system (SLc, Gebauer, Neuhausen, Germany) equipped with 400-MUm (n = 4), 450-MUm (n = 10), 500-MUm (n = 5), or 550-MUm (n = 5) heads. Central corneal thickness (CCT) and posterior and anterior lamellar thicknesses were measured using ultrasound pachymetry (Pachette 3; DGH Technology Inc, PA) and anterior segment optical coherence tomography (Casia SS-1000; Tomey, Nagoya, Japan). Endothelial viability [endothelial cell density (ECD)] was measured using trypan vital staining. RESULTS: CCT measured 595 +/- 66 MUm (n = 48) on arrival, 846 +/- 131 MUm (n = 48) after organ culture, and 565 +/- 58 MUm (n = 48) after deturgescence. CCT did not differ between study and control eyes. Posterior lamellar thickness measured 88 +/- 18 MUm (n = 24) immediately after dissection, 126 +/- 30 MUm (n = 24) 1 hour after dissection, and 131 +/- 41 MUm (n = 24) 2.3 +/- 0.6 days after dissection. ECD measured 2637 +/- 264 cells per square millimeter (n = 48) on arrival, 2524 +/- 232 cells per square millimeter (n = 48) after organ culture, 2493 +/- 253 cells per square millimeter (n = 48) after dissection, and 2311 +/- 218 cells per square millimeter (n = 48) 2.3 +/- 0.6 days after dissection. ECD did not differ between study and control eyes at all time points. CONCLUSIONS: Single-pass motor-driven linear microkeratome dissection provides an accurate and safe alternative for harvesting ultrathin endothelial lamellae from organ-cultured donor corneas. PMID- 26555593 TI - Infectious Keratitis in Limbal Stem Cell Deficiency: Stevens-Johnson Syndrome Versus Chemical Burn. AB - PURPOSE: To investigate the incidence, clinical and microbiological characteristics, risk factors, and therapeutic outcome of infectious keratitis in patients with limbal stem cell deficiency (LSCD) related to Stevens-Johnson syndrome (SJS) and corneal chemical burn. METHODS: Medical records of 90 eyes of 59 patients who were diagnosed with LSCD resulting from SJS (52 eyes of 29 patients) or corneal chemical burn (38 eyes of 30 patients) were reviewed. RESULTS: Infectious keratitis developed in 35% of LSCD patients with SJS (18 eyes, 14 patients) and in 18% of those with chemical burn (7 eyes, 7 patients). The development of infectious keratitis in SJS was significantly associated with the severity of chronic ocular surface complications in the cornea, conjunctiva, and eyelids and with the use of topical corticosteroids during the disease course. All cases of infectious keratitis following chemical burn occurred in patients with grade III or IV burn by Roper-Hall classification. Approximately 83% of culture-proven cases of infectious keratitis were bacterial infection, most of which (80%) were caused by Gram-positive bacteria. For resolution of infection, 17 eyes (68%) received surgery in addition to medical treatment, whereas 8 eyes (32%) received medical treatment alone. After infection resolution, the final visual acuity was decreased in 10 eyes (40%) compared with before infection. CONCLUSIONS: Infectious keratitis is a common complication of LSCD associated with SJS or severe chemical burn to the cornea. Despite medical and surgical treatments, the visual outcome is poor. PMID- 26555594 TI - Time Course of Antibiotic and Antifungal Concentrations in Corneal Organ Culture. AB - PURPOSE: Contamination with bacteria and/or fungi is a serious complication in organ-cultured corneas. Hence, antibiotic and antifungal agents are added to the culture medium. The concentration of different antimicrobial and antifungal additives to the media over time has so far not been investigated in detail and is the aim of this study. METHODS: Nine human fresh corneoscleral discs were stored in corneal culture medium consisting of 2% fetal bovine serum and minimal essential medium. In addition, the culture medium contained 1200 MUg/mL penicillin G, 25 MUg/mL amphotericin B, 120 MUg/mL streptomycin, and 100 MUg/mL voriconazole. The concentration of amphotericin B used was 10 times higher than in clinical routine to facilitate its detection. The cultures were kept at 37 degrees C for 28 days. At days 0, 7, 14, 21, and 28, samples of the culture medium were harvested for analysis of antimicrobial concentrations by liquid chromatography and electrospray ionization tandem mass spectrometry. RESULTS: During corneal storage, the concentration of all antibiotics and antifungal agents declined significantly. By day 28, penicillin G was reduced to 14% of the original concentration. Amphotericin B and streptomycin retained approximately 60% of the original concentration to the end of the experiment and voriconazole maintained stable concentrations after an initial decline to approximately 80% at 7 days. CONCLUSIONS: Throughout the entire storage period, the concentrations of penicillin G, streptomycin, and voriconazole exceeded the minimum inhibitory concentrations of all common contaminants, obviating the need for a change of the medium for antimicrobial reasons. Based on the minimum inhibitory concentrations and our findings, the initial concentration of amphotericin B should be raised to 5 MUg/mL. PMID- 26555595 TI - Individualized Exercise Training at Maximal Fat Oxidation Combined with Fruit and Vegetable-Rich Diet in Overweight or Obese Women: The LIPOXmax-Reunion Randomized Controlled Trial. AB - OBJECTIVES: Lifestyle combined interventions are a key strategy for preventing type-2 diabetes (T2DM) in overweight or obese subjects. In this framework, LIPOXmax individualized training, based on maximal fat oxidation [MFO], may be a promising intervention to promote fat mass (FM) reduction and prevent T2DM. Our primary objective was to compare three training programs of physical activity combined with a fruit- and vegetable-rich diet in reducing FM in overweight or obese women. DESIGN AND SETTING: A five months non-blinded randomized controlled trial (RCT) with three parallel groups in La Reunion Island, a region where metabolic diseases are highly prevalent. SUBJECTS: One hundred and thirty-six non diabetic obese (body mass index [BMI]: 27-40 kg/m2) young women (aged 20-40) were randomized (G1: MFO intensity; G2: 60% of VO2-peak intensity; G3: free moderate intensity at-home exercise following good physical practices). OUTCOMES: Anthropometry (BMI, bodyweight, FM, fat-free mass), glucose (fasting plasma glucose, insulin, HOMA-IR) and lipid (cholesterol and triglycerides) profiles, and MFO values were measured at month-0, month-3 and month-5. RESULTS: At month 5, among 109 women assessed on body composition, the three groups exhibited a significant FM reduction over time (G1: -4.1+/-0.54 kg; G2: -4.7+/-0.53 kg; G3: 3.5+/-0.78 kg, p<0.001, respectively) without inter-group differences (p = 0.135). All groups exhibited significant reductions in insulin levels or HOMA-IR index, and higher MFO values over time (p<0.001, respectively) but glucose control improvement was higher in G1 than in G3 while MFO values were higher in G1 than in G2 and G3. Changes in other outcome measures and inter-group differences were not significant. CONCLUSION: In our RCT the LIPOXmax intervention did not show a superiority in reducing FM in overweight or obese women but is associated with higher MFO and better glucose control improvements. Other studies are required before proposing LIPOXmax training for the prevention of T2DM in overweight or obese women. TRIAL REGISTRATION: ClincialTrials.gov NCT01464073. PMID- 26555596 TI - Continuous Distributed Representation of Biological Sequences for Deep Proteomics and Genomics. AB - We introduce a new representation and feature extraction method for biological sequences. Named bio-vectors (BioVec) to refer to biological sequences in general with protein-vectors (ProtVec) for proteins (amino-acid sequences) and gene vectors (GeneVec) for gene sequences, this representation can be widely used in applications of deep learning in proteomics and genomics. In the present paper, we focus on protein-vectors that can be utilized in a wide array of bioinformatics investigations such as family classification, protein visualization, structure prediction, disordered protein identification, and protein-protein interaction prediction. In this method, we adopt artificial neural network approaches and represent a protein sequence with a single dense n dimensional vector. To evaluate this method, we apply it in classification of 324,018 protein sequences obtained from Swiss-Prot belonging to 7,027 protein families, where an average family classification accuracy of 93%+/-0.06% is obtained, outperforming existing family classification methods. In addition, we use ProtVec representation to predict disordered proteins from structured proteins. Two databases of disordered sequences are used: the DisProt database as well as a database featuring the disordered regions of nucleoporins rich with phenylalanine-glycine repeats (FG-Nups). Using support vector machine classifiers, FG-Nup sequences are distinguished from structured protein sequences found in Protein Data Bank (PDB) with a 99.8% accuracy, and unstructured DisProt sequences are differentiated from structured DisProt sequences with 100.0% accuracy. These results indicate that by only providing sequence data for various proteins into this model, accurate information about protein structure can be determined. Importantly, this model needs to be trained only once and can then be applied to extract a comprehensive set of information regarding proteins of interest. Moreover, this representation can be considered as pre-training for various applications of deep learning in bioinformatics. The related data is available at Life Language Processing Website: http://llp.berkeley.edu and Harvard Dataverse: http://dx.doi.org/10.7910/DVN/JMFHTN. PMID- 26555597 TI - From the Skin to the Brain: Pathophysiology of Colonization and Infection of External Ventricular Drain, a Prospective Observational Study. AB - Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 +/-1.4 vs 24 +/-1.5 days, p<0.0001). Sixty-one (52%) and 32 (27%) skin and stopcock sites were colonized with commensal bacteria, 1 (1%) and 1 (1%) with pathogens, 8 (7%) and 1 (1%) with combined pathogens and commensal bacteria, respectively. Sixteen positive events were diagnosed; a cutaneous origin was identified in 69% of cases. The presence of a pathogen at skin site (6/16 vs 4/85, OR: 11.8, [2.5 56.8], p = 0.002) and CSF leakage (7/16 vs 6/85, OR 10 [2.4-41.2], p = 0.001)) were the two independent significant risk factors statistically linked to positive events occurrence. Our results suggest that VRC and VRI mainly results from an extra-luminal progression of pathogens initially colonizing the skin site where CSF leaks. PMID- 26555598 TI - A Novel Integrated Score Index of Echocardiographic Indices for the Evaluation of Left Ventricular Diastolic Function. AB - BACKGROUND: We propose a novel integrated score index, which could be used to quantify and grade left ventricular (LV) diastolic function. METHODS: We enrolled 629 participants [393 healthy subjects, 145 with hypertension (HTN), 24 with hypertrophic cardiomyopathy (HCM), and 67 with coronary artery disease (CAD)]. This score index was with a score of 1 for an E/A ratio < 1, a score of 1 for a septal e'/a' ratio <= 0.8, a score of 2 for a lateral e'/a' ratio <= 1, a score of 2 for a septal E/e' ratio >=10-15, a score of 3 for a lateral E/e' ratio >=8 15, and a score of 1 for a deceleration time >240 ms. The sum of each score was considered as the final value in this scoring method (either a septal or a lateral E/e' ratio > 15 was given a total score of 10, regardless of the other measurements). RESULTS: After analysis, the AUROC of this integrated score index for predicting any diastolic dysfunction (discriminated by the American Society of Echocardiography guidelines) was 0.962, and the AUROC of the method from the logistic regression was 0.970. The mean values of the score index for the groups were 3.81 +/- 0.12 in healthy, 6.48 +/- 0.19 in HTN, 7.35 +/- 0.46 in HCM, and 6.62 +/- 0.29 in CAD. Using the score index, the healthy subjects obtained lower scores compared with those of HTN (p = 0.00), HCM (p = 0.00), and CAD (p = 0.00). Therefore, this score index could discriminate patients with diseases with impaired diastolic function from the healthy subjects when the total sum of the score was equal to or greater than 4. CONCLUSIONS: If the presently used methods cannot allow the clear diagnosis of LV diastolic dysfunction, this integrated score index might be helpful for discriminating diseases with impaired diastolic function. PMID- 26555599 TI - dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs. AB - The purpose of the dbNSFP is to provide a one-stop resource for functional predictions and annotations for human nonsynonymous single-nucleotide variants (nsSNVs) and splice-site variants (ssSNVs), and to facilitate the steps of filtering and prioritizing SNVs from a large list of SNVs discovered in an exome sequencing study. A list of all potential nsSNVs and ssSNVs based on the human reference sequence were created and functional predictions and annotations were curated and compiled for each SNV. Here, we report a recent major update of the database to version 3.0. The SNV list has been rebuilt based on GENCODE 22 and currently the database includes 82,832,027 nsSNVs and ssSNVs. An attached database dbscSNV, which compiled all potential human SNVs within splicing consensus regions and their deleteriousness predictions, add another 15,030,459 potentially functional SNVs. Eleven prediction scores (MetaSVM, MetaLR, CADD, VEST3, PROVEAN, 4* fitCons, fathmm-MKL, and DANN) and allele frequencies from the UK10K cohorts and the Exome Aggregation Consortium (ExAC), among others, have been added. The original seven prediction scores in v2.0 (SIFT, 2* Polyphen2, LRT, MutationTaster, MutationAssessor, and FATHMM) as well as many SNV and gene functional annotations have been updated. dbNSFP v3.0 is freely available at http://sites.google.com/site/jpopgen/dbNSFP. PMID- 26555600 TI - Linking Microbiota to Human Diseases: A Systems Biology Perspective. AB - The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction. PMID- 26555601 TI - The 'Omics' of Voluntary Exercise: Systems Approaches to a Complex Phenotype. AB - Predisposition to engage in exercise is highly variable and simultaneously influenced by the environment, complex genomics, and their interactions. Given the importance of exercise to health, understanding the underlying influences of variability is crucial. Here, we discuss murine systems approaches, focusing on 'omics', relevant to revealing the architecture of voluntary activity. PMID- 26555602 TI - One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure. AB - AIMS: AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow up. This report presents the results from 1 year of extended follow up for this clinical trial. METHODS AND RESULTS: We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF <=35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 +/- 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. CONCLUSIONS: Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy. PMID- 26555603 TI - Quaternary Triphenylphosphonium Compounds: A New Class of Environmental Pollutants. AB - A nontarget screening using high-resolution mass spectrometry (HRMS) was established to identify industrial emerging contaminants in the Rhine River. With this approach, quaternary triphenylphosphonium compounds (R-Ph3P(+)) were identified as new emerging contaminants in the aquatic environment. The suggested chemical structures were elucidated by MS fragmentation and chemical databank searches and eventually confirmed via authentic standards. R-Ph3P(+) are used worldwide by the chemical industry to synthesize alkenes via the Wittig reaction. In total, five compounds [R = butyl (Bu), R = ethyl (Et), R = methoxymethyl (MeOMe), R = methyl (Me), and R = phenyl (Ph)] were found in German rivers and streams. R-Ph3P(+) were detected only in those rivers and streams that received an appreciable portion of wastewater from the chemical industry. Up to 2.5 MUg/L Et-Ph3P(+) was quantified in a small stream from the Hessian Ried, and in the Rhine, up to 0.56 MUg/L Me-Ph3P(+) was detected. R-Ph3P(+) were also identified in suspended particulate matter and sediments in the Rhine catchment, with MeOMe Ph3P(+) concentrations of up to 0.75 mg/kg and up to 0.21 mg/kg, respectively. Because of the lack of ecotoxicological studies, the environmental risks caused by R-Ph3P(+) can be assessed for neither pelagic nor benthic organisms. PMID- 26555604 TI - Suicide attempts in bipolar disorders: comprehensive review of 101 reports. AB - OBJECTIVE: Assess reported risk of suicide attempts by patients with bipolar disorder (BD). METHOD: Systematic searching yielded 101 reports from 22 countries (79 937 subjects). We analyzed for risk (%) and incidence rates (%/year) of attempts, comparing sex and diagnostic types, including by meta-analysis. RESULTS: Attempt risk averaged 31.1% [CI: 27.9-34.3] of subjects, or 4.24 [3.78 4.70]%/year. In BD-I (43 studies) and BD-II subjects (30 studies), risks (29.9%, 31.4%) and incidence rates (4.01, 4.11%/year) were similar and not different by meta-analysis. Among women vs. men, risks (33.7% vs. 25.5%) and incidence (4.50 vs. 3.21%/year) were greater (also supported by meta-analysis: RR = 1.35 [CI: 1.25-1.45], P < 0.0001). Neither measure was related to reporting year, % women/study, or to onset or current age. Risks were greater with longer exposure, whereas incidence rates decreased with longer time at risk, possibly through 'dilution' by longer exposure. CONCLUSION: This systematic update of international experience underscores high risks of suicide attempts among patients with BD (BD-I = BD-II; women > men). Future studies should routinely include exposure times and incidence rates by diagnostic type and sex for those who attempt suicide or not. PMID- 26555605 TI - Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial. AB - BACKGROUND AND OBJECTIVES: The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists. RESULTS: At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2). CONCLUSIONS: Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring. PMID- 26555606 TI - Neuroticism in Remitted Major Depression: Elevated with Early Onset but Not Late Onset of Depression. AB - BACKGROUND: The personality trait of neuroticism is strongly related to depression, but depression is etiologically heterogeneous. Late-onset depression (LOD) may be more closely related to vascular factors, and previous studies of neuroticism in LOD versus early-onset depression (EOD) have not been consistent. METHOD: We examined neuroticism, extraversion and perceived stress in 88 fully remitted depressed patients with a mean age of 60 years and with a history of hospitalization for major depressive disorder. Patients were divided into those with onset after and those with onset before 50 years of age (LOD and EOD, respectively), and the two groups were compared both with each other and with matched control groups of healthy subjects. RESULTS: EOD patients showed increased levels of neuroticism in comparison with both LOD and matched controls, who did not differ. The association between age of onset and neuroticism was confirmed in analyses based on age of depression onset as a continuous variable. CONCLUSION: Neuroticism may be an etiological factor in EOD but not or less so in LOD. This finding contributes to the growing evidence for etiological differences between early- and late-onset late-life depression. PMID- 26555610 TI - Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes. AB - The aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 MUM and 29.1 MUM, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa. PMID- 26555609 TI - NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions. AB - Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson's disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2 PINK1 signaling axis is deeply involved in cell survival. PMID- 26555611 TI - The Mechanism in Gastric Cancer Chemoprevention by Allicin. AB - Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/ independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer. PMID- 26555612 TI - Leuckart Synthesis and Pharmacological Assessment of Novel Acetamide Derivatives. AB - A new concatenation of N-(1-(4-bromophenyl)ethyl)-2-phenoxyacetamide and N-(1-(4 methoxyphenyl) ethyl)-2-phenoxyacetamide derivatives having 2-phenoxy-N-(1 phenylethyl)acetamide nucleus as common in both the types was synthesized for the sake of achieve titled compounds as potential cytotoxic, anti-inflammatory, analgesic and antipyretic agents. All the novel derivatives have been synthesized through multi-step reaction sequence starting from Leuckart reaction. The structural assignments of the new compounds have been determined by virtue of their IR, 1H NMR, 13C NMR, elemental analysis and mass spectrum analysis. All the synthesized compounds were assessed for cytotoxicity and anti-inflammatory, analgesic and antipyretic effects. Among the series, compounds 3a, 3c, 3g and 3h possess cytotoxic, anti-inflammatory, analgesic and antipyretic activities comparable with standard drugs. The synthesized compounds were found to be active because of the presence of bromo, tert- butyl and nitro groups at position 4 of phenoxy nucleus. PMID- 26555613 TI - Establishment of Green Fluorescent Protein and Firefly Luciferase Expressing Mouse Primary Macrophages for In Vivo Bioluminescence Imaging. AB - Macrophages play a key role in tissue homeostasis as well as in a range of pathological conditions including atherosclerosis, cancer, and autoimmunity. Many aspects of their in vivo behavior are, however, poorly understood. Bioluminescence imaging (BLI) with green fluorescent protein (GFP) and firefly luciferase (FLUC) labelled autologous reporter macrophages could potentially offer a powerful tool to study macrophage biology, but this approach has been hindered by the relative difficulty of efficient gene transfer into primary macrophages. Here we describe a straightforward method for producing large numbers of GFP/FLUC expressing mouse primary macrophages utilizing lentivirus vector, cyclosporine, and a double infection strategy. Using this method we achieved up to 60% of macrophages to express GFP with correspondingly high FLUC signal. When injected into the circulation using a mouse model of local biomaterial induced inflammation and osteolysis, macrophages were initially detectable within the lungs, followed by systemic homing to the local area of chronic inflammation in the distal femur. In addition, transduced macrophages maintained their ability to assume M1 and M2 phenotypes although the GFP/FLUC expression was altered by the polarizing signals. These reporter macrophages could prove to be valuable tools to study the role of macrophages in health and disease. PMID- 26555614 TI - m-Trifluoromethyl-diphenyldiselenide as a pharmacological tool to treat preference symptoms related to AMPH-induced dependence in rats. AB - Amphetamine (AMPH) abuse is a world concern and a serious public health problem. Repeated administration of high doses of AMPH induces neuropsychiatric consequences, including addiction, reward and psychosis, whose pharmacological treatment has shown limited effectiveness. The m-trifluoromethyl diphenyldiselenide [(m-CF3-PhSe)2] has been documented as a promising pharmacological agent in different animal models related to oxidative damage. In this study, we examined the influence of (m-CF3-PhSe)2 on withdrawal following re exposure to AMPH. Wistar rats received d,l-AMPH or saline in the conditioned place preference (CPP) paradigm for 8days. Then, half of each initial (AMPH or saline) experimental group was treated with (m-CF3-PhSe)2 or vehicle, resulting in four final groups: i) Saline/vehicle; ii) (m-CF3-PhSe)2/saline; iii) AMPH/vehicle; and iv) AMPH/(m-CF3-PhSe)2. After fourteen days of (m-CF3-PhSe)2 treatment, animals were re-exposed to AMPH or vehicle in the CPP paradigm for three more days in order to assess drug re-conditioning and memory/locomotor activity, performed 24h after AMPH re-exposure in the CPP and the Y maze, respectively. Subsequently, ex-vivo assays were carried out in samples of the prefrontal cortex (PFC) of the animals. The (m-CF3-PhSe)2 treatment was able to prevent AMPH-induced re-conditioning symptoms in rats. Behavioral observations in the Y maze task showed no significant changes. AMPH exposure was able to increase 5-HT uptake as well as oxidative damage in the PFC, whereas (m-CF3-PhSe)2 treatment exerted a preventative effect against these alterations. The current findings suggest that (m-CF3-PhSe)2 might be considered a promising therapeutic tool for AMPH-induced addiction. PMID- 26555615 TI - Nanoparticulate fingolimod delivery system based on biodegradable poly (3 hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): design, optimization, characterization and in-vitro evaluation. AB - This study was focused on the fabrication, statistical optimization and in vitro characterization of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles loaded with fingolimod. PHBV-based fingolimod nanoparticles were prepared by single and double evaporation methods; the incorporation efficiency of fingolimod was higher with the single emulsion evaporation method in the nanosize range particles. Fingolimod HCL was neutralized with NaOH in order to slow down the release of the highly soluble fingolimod. The encapsulation efficiency of neutralized fingolimod was much higher (53-73%) due to the insoluble form of the drug used in encapsulation. It was found that the amount of fingolimod, concentration of PHBV and polyvinyl alcohol (PVA) would influence the encapsulation efficiency significantly. The effect of these parameters on the Particle size, PdI, loading capacity and loading efficacy was studied. The optimum conditions were 1.32% PHBV, 0.42% PVA and 5 mg fingolimod. The average size of optimized nanoparticles which measured with the aid of the Box-Behnken experimental design was 250 nm and entrapment efficiency of 73(%). Drug-release from the nanospheres over a four-week period has shown a characteristic triphasic release pattern with an initial burst effect. PMID- 26555616 TI - Association of Thyroid-Stimulating Hormone with Resting Energy Expenditure in Euthyroid Elderly Subjects: A Cross-Sectional Study. AB - BACKGROUND: Several studies have reported positive correlations between thyroid stimulating hormone (TSH) and body mass index (BMI) in euthyroid subjects. As impaired thyroid function is known to affect the metabolic rate, this study investigated whether TSH is associated with resting energy expenditure (REE) in euthyroid elderly subjects, independent of age, anthropometric data and body composition. METHODS: Cross-sectional data of 77 women (66-96 years, BMI 18-36 kg/m2) and 55 men (66-86 years, BMI 20-39 kg/m2) were analyzed. REE was measured using indirect calorimetry, body composition by bioelectrical impedance analysis and serum TSH using an electrochemiluminescence immunoassay. RESULTS: REE, fat free mass (FFM) and waist circumference (WC) were significantly lower, whereas TSH and fat mass (FM) were significantly higher in women than in men. In multiple stepwise regression analysis, with age-adjusted REE (REE(adj)) as the dependent variable and FFM, FM and WC as independent variables, FFM and WC explained 40.7% in women and FFM 32.8% in men of the variability in REE(adj). Including TSH in the model led to a significant rise of the adjusted R-squared value in women only, and explained an additional 2.8% of the variability in REE(adj). CONCLUSIONS: TSH is independently and negatively associated with REE in euthyroid elderly women. PMID- 26555617 TI - Differential Support of Aspergillus fumigatus Morphogenesis by Yeast and Human Actins. AB - The actin cytoskeleton is highly conserved among eukaryotes and is essential for cellular processes regulating growth and differentiation. In fungi, filamentous actin (F-actin) orchestrates hyphal tip structure and extension via organization of exocytic and endocytic processes at the hyphal tip. Although highly conserved, there are key differences among actins of fungal species as well as between mammalian and fungal actins. For example, the F-actin stabilizing molecules, phalloidin and jasplakinolide, bind to actin structures in yeast and human cells, whereas phalloidin does not bind actin structures of Aspergillus. These discrepancies suggest structural differences between Aspergillus actin filaments and those of human and yeast cells. Additionally, fungal actin kinetics are much faster than those of humans, displaying 5-fold faster nucleation and 40-fold faster nucleotide exchange rates. Limited published studies suggest that these faster actin kinetics are required for normal growth and morphogenesis of yeast cells. In the current work, we show that replacement of Aspergillus actin with yeast actin generates a morphologically normal strain, suggesting that Aspergillus actin kinetics are similar to those of yeast. In contrast to wild type A. fumigatus, F-actin in this strain binds phalloidin, and pharmacological stabilization of these actin structures with jasplakinolide inhibits germination and alters morphogenesis in a dose-dependent manner. We also show that human beta actin cannot support Aspergillus viability, even though the amino acid sequences of human and Aspergillus actins are 89.3% identical. Our findings show that minor differences in actin protein sequence account for loss of phalloidin and jasplakinolide sensitivity in Aspergillus species. PMID- 26555618 TI - Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa. AB - Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive - running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity. PMID- 26555620 TI - Humpback Dolphins: A Brief Introduction to the Genus Sousa. AB - The delphinid genus Sousa has recently undergone a major revision, and currently contains four species, the Atlantic humpback (Sousa teuszii), Indian Ocean humpback (Sousa plumbea), Indo-Pacific humpback (Sousa chinensis), and Australian humpback (Sousa sahulensis) dolphins. Recent molecular evidence suggests that humpback dolphins in the Bay of Bengal may comprise a fifth species. These moderate-sized dolphin species are found in shallow (<30m), coastal waters of the eastern Atlantic, Indian, and western Pacific oceans. Abundance and trends have only been studied in a few areas, mostly in eastern Africa, China, and northern Australia. No global, empirically derived abundance estimates exist for any of the four species, but none appear to number more than about 20,000 individuals. Humpback dolphins feed mostly on small fishes, and sometimes shrimps; occur for the most part in small groups (mostly 12 or less); have limited nearshore movements; and in most parts of their range exhibit a fission/fusion type of social organization. Major threats that affect all the species are entanglement in fishing gear, and habitat degradation/destruction from various forms of coastal development. Impacts from vessel traffic (including behavioural disturbance and displacement, as well as mortality and morbidity from collisions with vessels) appear to be significant in most areas. Several other threats are apparently significant only in particular parts of the range of some species (e.g. high levels of organochlorine contaminants affecting Indo-Pacific humpback dolphins in Hong Kong). Direct hunting only occurs in limited areas and primarily on a small scale. Conservation actions so far have been limited, with most populations receiving little study and almost no management attention. Much more work is needed on humpback dolphin population status, threats, and how the major threats can be reduced or eliminated. Extinction risks for the four species and some populations are preliminarily re-assessed using the IUCN Red List criteria in the current volume. The results suggest that all four species in the genus are threatened at some level (suggested Red List status ranges from Vulnerable for S. chinensis and S. sahulensis to Critically Endangered for S. teuszii). PMID- 26555619 TI - [Adequate fluid resuscitation in septic shock with high catecholamine doses]. AB - BACKGROUND: Appropriate fluid resuscitation is a fundamental aspect for the hemodynamic management of septic shock patients and should ideally be achieved before vasopressors and positive inotropic substances are administered. The development of hemodynamic monitoring has revealed that in some cases patients had been improperly treated with high-dose catecholamines for initially insufficient fluid resuscitation. The aim of this study was to show that in some cases it is possible to actively reduce catecholamines by a volume challenge adapted according to the individual patient needs. MATERIAL AND METHODS: In this retrospective observational study 29 patients with septic shock in a surgical intensive care unit (ICU) at a university hospital (17 male, 12 female, mean age 71 +/- 10 years) on high-dose catecholamines (median values norepinephrine 0.204 ug/kg body weight/min, dobutamine 3.876 ug/kg/min and epinephrine 0.025 ug/kg/min, ranging up to 0.810 ug/kg/min, 22.222 ug/kg/min and 0.407 ug/kg/min in 28, 20 and 17 patients, respectively) were analyzed. The extremities of the patients were initially cold with a mottled marbled appearance whereas the mean arterial pressure (MAP) was >= 65 mmHg. The median central venous pressure (CVP) was 17 mmHg (range 55-34 mmHg) and the mean lactate concentration was 2.78 mmol/l (range 0.93-10.67 mmol/l). The standard therapy concept consisted of a forced volume challenge combined with active reduction of catecholamines to achieve an adequate fluid loading status, guided by the passive leg raising test (PLR), clinical signs and in 19 cases by hemodynamic monitoring (pulmonary artery catheter Vigilance II(TM) n = 10, FloTrac(TM), Vigileo(TM) n = 9 and PreSep(TM) n = 5; Edwards Life Sciences). The forced volume challenge was stopped after clinical improvement with rewarmed extremities, increasing diuresis volumes and lack of improvement by PLR. RESULTS: Catecholamine doses could be significantly reduced in all patients: norepinephrine to 0 ug/kg/min, dobutamine to 1.852 ug/kg/min and epinephrine to 0 ug/kg/min (up to 0.133 ug/kg/min, 6.289 ug/kg/min and 0.091 ug/kg/min, respectively, p < 0.05 Wilcoxon signed rank test). Volume challenge test: + 4,500 ml Ringer solution (range 0-24,000 ml) and 1,000 ml hydroxyethyl starch (range 0-2,500 ml) and mean fluid balance + 6,465 ml (range + 2,040 ml to + 27,255 ml). The median weaning time from catecholamines was 12 h (range 4-43 h). After treatment all patients showed rewarmed extremities and a decrease in mean lactate levels from 2.78 mmol/l (range 0.93-10.67 mmol/l) to 2.05 mmol/l (range 0.7-5.4 mmol/l). The measured hemodynamic constellations showed clear interindividual differences but no cardiac deterioration occurred. The median oxygenation index (paO2/FiO2) showed a statistically insignificant change from 264 mmHg (range 75-418 mmHg) to 250 mmHg (range 120-467 mmHg). Of the patients 20 survived and 9 died. CONCLUSION: It is possible to wean a substantial proportion of septic shock patients from high-dose catecholamines in combination with a needs-adapted forced volume challenge test. The importance of appropriate fluid loading prior to the use of high catecholamine doses should be a main subject of discussion in patients with severe septic shock and was confirmed in this study. This should be oriented to clinical and if possible, hemodynamic parameters and should not be underestimated. PMID- 26555621 TI - Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities. AB - Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. PMID- 26555622 TI - Re-assessment of the Conservation Status of the Atlantic Humpback Dolphin, Sousa teuszii (), Using the IUCN Red List Criteria. AB - The Atlantic humpback dolphin (Sousa teuszii) is an obligate shallow water dolphin that is endemic to the western coasts of Africa, ranging from Western Sahara to Angola. The species occurs exclusively in a limited number of near shore habitats, a tendency that routinely exposes it to a suite of lethal and deleterious anthropogenic threats. These include habitat degradation, accidental capture in artisanal fishing nets, and hunting for use as food and bait. The species also competes with rapidly expanding human populations for coastal resources in some of the poorest countries on Earth. Data for most aspects of the species' ecology are sparse, but S. teuszii is considered by most qualified observers to be rare and greatly threatened. A lack of appropriate survey data precludes a quantitative assessment of population trends and status. Most populations for which any data are available are considered to be extremely small, numbering in the tens or low hundreds of individuals. The available published estimates suggest that the total population likely falls below 3000 individuals. Declines in abundance have been observed or are suspected for each population and will continue, given projected expansions of identified threats that affect most of the species' known range, and a corresponding lack of appropriate management actions. The apparent scale of threats, the presumed isolation of most populations, and a lack of directed conservation efforts in most areas suggest that the species qualifies for a listing of Critically Endangered (under criteria A3cd) on the IUCN Red List. PMID- 26555623 TI - A Review of the Geographical Distribution and Habitat of the Atlantic Humpback Dolphin (Sousa teuszii). AB - Understanding of the distributional ecology of the Atlantic humpback dolphin (Sousa teuszii) has been hampered by a lack of systematic and consistent sampling effort. The only comprehensive species distribution review was published in 2004; since then a considerable amount of novel information has emerged. We compiled 853 sighting, capture and specimen records of the species, and produced global and regional distribution maps. Of the 830 records where year was available, 63.1% dated from >=2005 and confirm a contemporary occurrence in six marine ecoregions and 11 countries: Western Sahara, Mauritania, Senegal, Gambia, Guinea Bissau, Guinea, Benin, Cameroon, Gabon, Congo Republic and Angola. Additionally, Togo is a recently confirmed range state. Group sizes ranged from 1 to 45 animals, with small groups of 1 to 10 animals comprising 65% of the sightings. Similarities were noted in the regions inhabited by Atlantic humpback dolphins across their range, particularly an occurrence in relatively shallow (predominantly <=20 m) depths, in warm waters (average SSTs of 15.8-31.8 degrees C) and in dynamic habitat strongly influenced by tidal patterns. These conditions occur in various habitats occupied by the species, including estuarine systems, open coasts, archipelagos, tidal mud-flats and sheltered bays. Sightings were recorded at distances of 13 m to 12.8 km (mean of 573 m) from land, indicating that the species occurs several kilometres from shore when suitable shallow habitat is present. The Atlantic humpback dolphin may be a 'nearshore' species based on oceanographic definitions incorporating water depth, wave action and sedimentation rather than on spatial distance from the coast. PMID- 26555624 TI - Assessment of the Conservation Status of the Indian Ocean Humpback Dolphin (Sousa plumbea) Using the IUCN Red List Criteria. AB - Indian Ocean humpback dolphins (Sousa plumbea) are obligate shallow-water dolphins that occur exclusively in the near-shore waters of the Indian Ocean, from South Africa to the Bay of Bengal. They have a narrow habitat preference, restricted distribution and do not appear very abundant across any part of their range. There is no estimate of total species abundance; all populations that have been quantitatively evaluated have been small in size, usually fewer than 200 individuals. Fishing, dredging, land reclamation, construction blasting, port and harbour construction, pollution, boat traffic and other coastal development activities all occur, or are concentrated within, humpback dolphin habitat and threaten their survival. Although data are far from sufficient to make a rigorous quantitative assessment of population trends for this species, the scale of threats is large enough over a significant enough portion of the range to suspect or infer a decline of at least 50% over three generations, which qualifies it for listing on the IUCN Red List as Endangered. The issue primarily responsible is incidental mortality in fisheries, but the loss and degradation of habitat is likely a contributing factor. None of the threats have been adequately addressed in any part of the species' range, even though threat levels are increasing virtually everywhere. PMID- 26555625 TI - The Natural History and Conservation of Indian Ocean Humpback Dolphins (Sousa plumbea) in South African Waters. AB - Although most knowledge on the biology of Sousa plumbea has primarily come from South African waters, a number of research gaps remain on the natural history and status of the species in the region. Research on two populations in South African waters for which some historical data exist may aid in highlighting long-term changes in the biology and natural history of this little known coastal delphinid. Recent studies on the age, growth and reproduction of animals incidentally caught in shark nets in Richards Bay, KwaZulu-Natal, yielded a lower maximum age estimate of 24 (previously 46) growth-layer-groups (GLGs), sexual maturity of 7.5 and 8 GLGs in males and females (previously 12-13 and 10 GLGs, respectively), an ovulation rate of 0.2 and a 5-year calving interval (previously 0.3 and 3-year calving interval) than previously reported. These differences may be due to a difference in the interpretation of GLGs between observers or a predominance of young males being caught in the shark nets. Stomach content analysis revealed a change in the relative proportions of the main prey items over the past 25 years, but no difference in species richness or diversity was found between the sexes. No change in trophic level was recorded between 1972 and 2009. Field studies in Algoa Bay, Eastern Cape, conducted 16 years apart indicated a decline in the mean group size (from 7 to 3 animals), a decline in the maximum group size (from 24 to 13 animals), an increase in solitary individuals (15.4-36%), and a change in behaviour from predominantly foraging (64 18%) to mainly travelling (24-49%). The observed changes are suggestive of a change in food availability, resulting in a range shift or a potential decline in numbers. These studies indicate the importance of long-term studies to monitor population changes and their possible causes. A number of threats, such as shark nets, pollution (noise and chemical), and coastal development and disturbance, to the humpback dolphin populations in South Africa have been identified. Urgent action is required to ensure continued existence of the species in South African waters. PMID- 26555626 TI - Ecology and Conservation Status of Indian Ocean Humpback Dolphins (Sousa plumbea) in Madagascar. AB - The Indian Ocean humpback dolphin (Sousa plumbea) has been studied in several range states in the Southwest Indian Ocean, however little information exists on populations in Madagascar. Here, we review available literature and describe a study on S. plumbea conducted between 2004 and 2013 on the west coast of Madagascar, involving boat-based field surveys in the southwest and northwest regions, and interview surveys with local fishers from villages along most of the west coast. Field surveys in the southwest region of Anakao/St. Augustine Bay revealed low encounter rates and mean group size, and markedly declining trends in both from 1999 to 2013. Conversely, in the northwest region around Nosy Be and Nosy Iranja, encounter rates were higher, as were mean group sizes, suggesting an apparently more abundant and less impacted population. Interview surveys revealed by-catch of coastal dolphins along the entire west coast, including S. plumbea, as well as other species. Directed hunting, including drive hunts of groups of dolphins, was reported primarily in the southern regions, in the range of the Vezo Malagasy ethnicity; however, there was evidence of hunting starting in one area in the northwest, where hunting dolphins is normally considered taboo for the predominant Sakalava ethnicity. Thus, the conservation status of S. plumbea in Madagascar appears to be spatially heterogeneous, with some areas where the local population is apparently more impacted than others. Conservation measures are recommended to mitigate further decline in the southwest of Madagascar, while protecting habitat and ensuring resilience in the northwest. PMID- 26555627 TI - A Review of the Status of the Indian Ocean Humpback Dolphin (Sousa plumbea) in Pakistan. AB - Limited historical and new information on Indian Ocean humpback dolphins, Sousa plumbea, in Pakistan are reviewed. Although present along most of the coast, S. plumbea concentrates in the mangrove-lined creek system of the Indus Delta (Sindh), Miani Hor (Sonmiani Bay), Kalmat Lagoon, Gwadar and the Dasht River estuary (Gwater Bay, Jiwani). Other areas of distribution comprise the Karachi coast, Kund Malir, Ormara and Pasni. In the Indus Delta, 46 small-boat surveys conducted monthly (minus July and October) in 2005-2009, documented 112 sightings (439 individuals) in major creeks, smaller channels and nearshore waters. Group sizes ranged from 1-35 animals (mean=3.92+/-4.60). Groups of 1-10 animals composed 91% of total (27.9% single animals). An encounter rate of 0.07-0.17 dolphins km(-1) lacked a significant trend across survey years. A discovery curve remained steep after 87 dolphins were photo-identified, suggesting the population is vastly larger. In Sonmiani Bay, Balochistan, during 9 survey days in 2011 2012, group sizes ranged from 1-68 animals (mean=11.9+/-13.59; n=36), totalling 428 dolphins. Incidental entanglements, primarily in gillnets, pollution (especially around Karachi), overfishing and the ship breaking industry in Gaddani, pose major threats. Incidental catches occur along the entire Pakistani coast. Of 106 stranded cetaceans, 24.5% were S. plumbea. Directed takes in Balochistan, driven by demand for bait in shark fisheries, have reportedly declined following dwindling shark stocks. Habitat degradation threats include depletion of prey and increased maritime traffic. Domestic sewage and solid waste pollution are predominant on the Balochistan coast, especially at Miani Hor, Kund Malir, Ormara, Kalmat Lagoon, Pasni, Gwadar and Jiwani. An exhaustive habitat assessment combined with appropriate fishery management is the only way to safeguard the future of S. plumbea in Pakistan. PMID- 26555628 TI - Humpback Dolphins (Genus Sousa) in India: An Overview of Status and Conservation Issues. AB - This chapter aims to collate recent work done by different research teams along the Indian coast and presents research plans for the conservation and management of the genus Sousa in Indian waters. Humpback dolphins are the most common nearshore cetaceans found along the Indian coast. The taxonomy is confused, but two or more species of humpback dolphins may be present in India. Dedicated research on humpback dolphins and other cetaceans has been initiated only in the past few years and vast gaps in the ecology and conservation of the genus from the region remain. Dedicated and opportunistic research indicates that humpback dolphin presence is continuous along the west coast of India, owing to the contiguous favourable habitat of shallow nearshore waters, while along the east coast humpback dolphins are apparently found in pockets. Humpback dolphins are also the most numerous in incidental catch records from the coast, owing to the large overlap in space use with nearshore fisheries like small gillnets, trawls, shore seines and purse seines. Along many coastal sites, humpback dolphins are known to cause damage and depredation of fish catch of certain fishing gears, making them unpopular. At the same time, many fishers along the west coast have developed local dolphin-watching programmes as an alternate source of livelihood, providing positive impetus for conservation. However, research on the long-term effects of dolphin watching and its management is required. Some recommendations for more effective management of this species are made. PMID- 26555629 TI - Preface. PMID- 26555630 TI - A cohort study of pyridoxine-dependent epilepsy and high prevalence of splice site IVS11+1G>A mutation in Chinese patients. AB - PURPOSE: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by mutations of the ALDH7A1 gene. We aimed to analyze the relations between the clinical diagnosis and treatment of PDE and ALDH7A1 gene mutations in Chinese PDE patients. METHODS: The clinical manifestations, diagnosis and treatment were observed in a cohort of PDE patients with early onset of seizure. Video-electroencephalogram (VEEG) and magnetic resonance imaging (MRI) were performed. The mutation of ALDH7A1 gene was analyzed. RESULTS: Of eight patients, six were males and two were females. Age of seizure onset ranged from 1 to 100 days and 75% patients presented with seizures in the neonatal period. All patients showed different degrees of developmental delay. EEGs showed focal or multifocal discharges, or were normal. Molecular analysis revealed 10 ALDH7A1 mutations, including 2 splice site mutations. Five patients had mutation at IVS11+1G>A site, six patients had missense mutations, one with nonsense mutation and another patient had 9-bp genomic deletion mutation. Among them, two mutations were first time reported. CONCLUSIONS: Seizure onset was in neonatal or early infantile period in our PDE patients. Early recognition and diagnosis of the disease is necessary for early intervention and improve cognitive development in the later life. In this study, on the molecular level, we also identified the splice site mutation IVS11+1G>A as a high prevalence mutation site with a frequency of 31.25% (5 of 16 alleles) in Chinese PDE patients. PMID- 26555631 TI - Do HLA-A markers predict skin-reactions from aromatic antiepileptic drugs in a Norwegian population? A case control study. AB - PURPOSE: Cutaneous adverse reactions (cADRs) from carbamazepine (CBZ) have been associated with human leukocyte antigens (HLA). Our aims were to assess the clinical usefulness of HLA-A*31:01 as a predictor of CBZ-induced cADRs in the Norwegian population and to explore whether cADRs from aromatic antiepileptic drugs (AEDs) in general might be linked with a common HLA-A-marker. MATERIALS AND METHODS: 86 ethnic Norwegians with a history of non-bullous cADRs from aromatic AEDs were included. 114 subjects tolerant to at least one aromatic AED were used as drug-specific controls. Complete HLA-A genotyping was performed. 1026 blood donors were used as population controls. RESULTS: Comparing all cADR subjects with controls and blood donors, there were no statistical differences for any HLA A allele, except for HLA-A*24 (p=0.022 vs. controls and p=0.014 vs. blood donors). When comparing tolerant controls with patients having had a cADR to one of the two most used drugs, CBZ (n=48) and lamotrigine (n=28), we found no significant associations for CBZ to HLA-A*31:01 or HLA-A*24:02, but for lamotrigine there was an association with HLA-A*24:02 (p=0.027). In patients developing cross-reactivity (n=14) to aromatic AEDs, the presence of HLA-A*31:01 or HLA-A*24:02 was not different compared to patients with a single cARD tolerant to at least one other drug. CONCLUSION: We question the clinical usefulness of HLA-A*31:01 as a marker for CBZ rash in the Norwegian population. A previously suggested protective effect of aromatic AED cross-reactivity from HLA-A*24:02 was not confirmed. The association between HLA-A*24:02 and lamotrigine-induced rash should be further investigated. PMID- 26555632 TI - Positive modulation of a neutral declarative memory by a threatening social event. AB - Memories can be altered by negative or arousing experiences due to the activation of the stress-responsive sympatho-adrenal-medullary axis (SYM). Here, we used a neutral declarative memory that was acquired during multi-trial training to determine the effect of a threatening event on memory without emotional valence. To this end, participants received a new threatening social protocol before learning pairs of meaningless syllables and were tested either 15 min, 2 days or 8 days after acquisition. We first demonstrated that this threatening social situation activates not only the SYM axis (Experiment 1) and the hypothalamus pituitary-adrenal axis (HPA; Experiment 2), but also, it improves the acquisition or early consolidation of the syllable pairs (Experiment 3). This improvement is not a transient effect; it can be observed after the memory is consolidated. Furthermore, this modulation increases the persistence of memory (Experiment 4). Thus, it is possible to affect memories with specific events that contain unrelated content and a different valence. PMID- 26555633 TI - Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress Evoked Dopamine Concentrations in the Rat Dorsal Striatum. AB - Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress). Impaired escape behavior is a result of stress-sensitized serotonin (5 HT) neuron activity in the dorsal raphe (DRN) and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA) levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS) and lateral (DLS) dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress. PMID- 26555634 TI - Acute effects of caffeine on choroidal thickness and ocular pulse amplitude. AB - OBJECTIVE: To explore ocular changes in healthy people after caffeine consumption. METHODS: This prospective observational study was carried out with students of the Turgut Ozal University Medical Faculty from May 15 to 15 December 2014. Enrolled in the study were 17 healthy subjects (n = 17 eyes), with a median age of 24 (IQR 1), ranging between 21 and 26 years. The control group (6 females, 11 males) aged between 23 and 28 (median 25 years [IQR 4.75]). For study, one eye from each participant was randomly selected. To obviate the effect of diurnal variations, tests were performed at the same time of the day (10:00 a.m.-12:00 p.m.). Each subject was given an ophthalmologic examination before the study to exclude those with undiagnosed ocular disease. Version 6.0 Cirrus high-definition optical coherence tomography (HD-OCT) (Carl Zeiss Meditec, Dublin, CA) was used to measure CT at the fovea, and 1500 MUm nasal and 1500 MUm temporal to the fovea. After baseline OCT measurements, participants were asked to have 200 mg oral caffeine intake or a placebo capsule (200 mg lactose powder). Two further OCT measurements were applied at the first and fourth hours of caffeine intake. All participants also had intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements recorded before, first and fourth hours of caffeine intake. IOP and OPA were measured using the dynamic contour tonometry (DCT) (Swiss Micro Technology AG, Port, Switzerland). RESULTS: The groups showed no significant difference by means of age, gender, spherical refraction and axial length (p > 0.05). Baseline choroidal thickness measurements of the study and control group showed no significant difference. Oral caffeine intake caused a significant reduction in choroidal thickness compared with baseline, at all three measurement points, (p < 0.05). There were no significant changes in IOP and OPA measurements compared with the baseline values (p > 0.05). The choroidal thickness still continued to decrease for at least 4 h following caffeine intake; whereas, the difference between 1 and 4 h was not statistically significant (p > 0.05). However, choroidal thicknesses, IOP and OPA values of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 and 4 h after placebo intake (p > 0.05). CONCLUSIONS: We found no significant change in IOP and OPA following oral 200 mg caffeine intake, while CT significantly decreased, for at least 4 h. PMID- 26555635 TI - Differences in biochemical bone markers by diabetes type and the impact of glucose. AB - BACKGROUND: Diabetes mellitus is associated with an increased fracture risk, however the fracture risk is 7 fold increased in patients with type 1 diabetes (T1D) and 1.4 fold increased in patients with type 2 diabetes (T2D) with decreased and increased bone mineral density, respectively. Oral ingestion of glucose causes an acute decrease in bone turnover markers, and thus glucose levels may affect bone turnover in diabetes. OBJECTIVE: The aim was to examine disparities in bone turnover markers between patients with T1D and T2D and evaluate the effect of glucose on bone turnover. METHODS: A cross-sectional study was conducted. Patients diagnosed with T1D (n=98) or T2D (n=96) were included from the outpatient clinics at two University Hospitals. All individuals had normal renal function. Glucose and bone turnover markers were measured in non fasting blood samples. RESULTS: P-procollagen type 1 amino terminal propeptide (P1NP), p-osteocalcin (OC), and s-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL) were lower in patients with T2D compared to T1D, and s osteoprotegerin (OPG) was higher in T2D. P-C-terminal cross-linked telopeptide of type-I collagen (CTX), p-fibroblast growth factor-23 (FGF-23), p-sclerostin, and p-undercarboxylated osteocalcin (ucOC) were similar in between the two groups of patients. Increasing non-fasting glucose levels were inversely related to p-CTX, p-P1NP, p-OC, and p-ucOC and directly related to s-OPG in simple linear and multiple linear regressions adjusted for factors influencing bone turnover markers including HbA1c. CONCLUSION: Bone turnover markers were lower in patients with T2D compared to T1D. Acute blood glucose alterations may change bone turnover mediated by OPG and have detrimental effects on bone health in diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT01870557. PMID- 26555636 TI - Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population. AB - While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case-control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45-74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p<0.05). There was a dose dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend<=0.006), where the risk was significantly increased by 4.32-8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02-21.18) for PINP and 4.92 (1.67-14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53-21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3-Q4) to those with low levels of PINP (Q1 Q3) and CTX-I (Q1-Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population. PMID- 26555637 TI - CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-beta3 function. AB - The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-beta3 (TGF-beta3). Overexpression of CCN4 enhanced TGF-beta3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF beta3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-beta3 and regulated the ability of TGF-beta3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-beta3. PMID- 26555639 TI - Developmental trajectories and milestones of lesbian, gay, and bisexual young people. AB - Lesbian, gay, and bisexual (LGB) young people experience a variety of developmental trajectories that consist of milestones, the sequence and timing of which differ across individuals. They include early feelings of being different from peers, the onset of same-sex attraction, questioning one's sexuality, first same-sex sexual experience, recognition and self-labelling, disclosure to others, first romantic relationship, and self-acceptance. The invention of 'gay youth' during the 1970s and 1980s is briefly reviewed with an emphasis on the ways in which the portrait created by early research fails to capture the developmental trajectories of millennial young people. Although some young people struggle with mental health problems as they navigate these milestones, research documents the complexity, variety, and normative nature of the vast majority of LGB young people. A growing chorus of developmental, behavioural, and social scientists now emphasize that many contemporary young people forego sexual confusion, recognize the sex or gender to which they are attracted to and love, and believe they are as mentally healthy as heterosexual young people. PMID- 26555638 TI - Crosstalk between RyR2 oxidation and phosphorylation contributes to cardiac dysfunction in mice with Duchenne muscular dystrophy. AB - BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) are at risk of developing cardiomyopathy and cardiac arrhythmias. Studies in a mouse model of DMD revealed that enhanced sarcoplasmic reticulum (SR) Ca(2+) leak contributes to the pathogenesis of cardiac dysfunction. In view of recent data suggesting the involvement of altered phosphorylation and oxidation of the cardiac ryanodine receptor (RyR2)/Ca(2+) release channel, we hypothesized that inhibition of RyR2 phosphorylation in a mouse model of DMD can prevent SR Ca(2+) leak by reducing RyR2 oxidation. METHODS AND RESULTS: Confocal Ca(2+) imaging and single RyR2 channel recordings revealed that both inhibition of S2808 or S2814 phosphorylation, and inhibition of oxidation could normalize RyR2 activity in mdx mice. Moreover, Western blotting revealed that genetic inhibition of RyR2 phosphorylation at S2808 or S2814 reduced RyR2 oxidation. Production of reactive oxygen species (ROS) in myocytes from mdx mice was reduced by both inhibition of RyR2 phosphorylation or the ROS scavenger 2-mercaptopropionyl glycine (MPG). Finally, it was shown that ROS production in mdx mice is proportional to the activity of RyR2-mediated SR Ca(2+) leak, and likely generated by Nox2. CONCLUSIONS: Increased ROS production in the hearts of mdx mice drives the progression of cardiac dysfunction. Inhibition of RyR2 phosphorylation can suppress SR Ca(2+) leak in mdx mouse hearts in part by reducing RyR2 oxidation. PMID- 26555640 TI - Measuring sun exposure in epidemiological studies: Matching the method to the research question. AB - Sun exposure has risks and benefits for health. Testing these associations requires tools for measuring sun exposure that are feasible and relevant to the time-course of the health outcome. Recent sun exposure, e.g. the last week, is best captured by dosimeters and sun diaries. These can also be used for medium term sun exposure e.g. over several weeks, but incur a high participant burden. Self-reported data on "typical time outdoors" for working and non-working days, is less detailed and not influenced by day-to-day variation. Over a longer period, e.g. the lifetime, or for particular life stages, proxies of sun exposure, such as latitude of residence or ambient ultraviolet (UV) radiation levels (from satellites or ground-level monitoring) can be used, with additional detail provided by lifetime sun exposure calendars that include locations of residence, usual time outdoors, and detail of sunburn episodes. Objective measures of lifetime sun exposure include microtopography of sun-exposed skin (e.g. using silicone casts) or conjunctival UV autofluorescence. Potential modifiers of the association between sun exposure and the health outcome, such as clothing coverage and skin colour, may also need to be measured. We provide a systematic approach to selecting sun exposure measures for use in epidemiological health research. PMID- 26555641 TI - Spectroscopic and molecular docking studies of binding interaction of gefitinib, lapatinib and sunitinib with bovine serum albumin (BSA). AB - The binding interactions of three kinds of tyrosine kinase inhibitors (TKIs), such as gefitinib, lapatinib and sunitinib, with bovine serum albumin (BSA) were studied using ultraviolet spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR) and molecular docking methods. The experimental results showed that the intrinsic fluorescence quenching of BSA induced by the three TKIs resulted from the formation of stable TKIs-BSA complexes through the binding interaction of TKIs with BSA. The stoichiometry of three stable TKIs-BSA complexes was 1:1 and the binding constants (Kb) of the three TKIs-BSA complexes were in the order of 10(4)M(-1) at 310 K, indicating that there was a strong binding interaction of the three TKIs with BSA. Based on the analysis of the signs and magnitudes of the free energy change (DeltaG(0)), enthalpic change (DeltaH(0)) and entropic change (DeltaS(0)) in the binding process, it can be deduced that the binding process of the three TKIs with BSA was spontaneous and enthalpy-driven process, and the main interaction forces between the three TKIs and BSA were van der Waals force and hydrogen bonding interaction. Moreover, from the results of CD, FT-IR and molecular docking, it can be concluded that there was a significant difference between the three TKIs in the binding site on BSA, lapatinib was located on site II (m) of BSA while gefitinib and sunitinib were bound on site I of BSA, and there were some changes in the BSA conformation when binding three TKIs to BSA but BSA still retains its secondary structure alpha-helicity. PMID- 26555642 TI - Sequence specific recognition of ssDNA by fluorophore 3-hydroxyflavone. AB - A fully water soluble 3-hydroxyflavone (3HF) derivative, N-(3-hydroxy-4' flavonyl)-N,N,N-trimethylammonium sulfate (3HFNMe3) was synthesized. Investigation of its emissions at varying wavelengths revealed that it had three emission bands of normal (N(*)), anionic (A(*)) and tautomeric (T(*)), in ultrapure water. Recognition of single-stranded ten ssDNA chains, having different nucleotide sequences was studied, using the ratiometric change of the intensities of the two bands (A(*)/T(*)), depending upon the varying environment of the 3HFNMe3 with different ssDNA chains. Addition of the ssDNA chains to the 3HFNMe3 solution caused gradual quenching of the A(*) band and had almost no effect on the T(*) band. As the ratios of the two bands (A(*)/T(*)) vs increasing amount of the ssDNAs generated characteristic curves for each ssDNA chain, it became possible to identify the chains with their characteristic curves. PMID- 26555643 TI - Adsorption of porphyrin and carminic acid on TiO2 nanoparticles: A photo-active nano-hybrid material for hybrid bulk heterojunction solar cells. AB - A photo-active nano-hybrid material consisting of titania nanoparticles, carminic acid, and sulphonic acid functionalized porphyrin is reported here. In an attempt to extend the absorption spectrum of titania to visible region by co-adsorbing carminic acid and sulphonic acid functionalized porphyrin on its surface. Interesting changes in the UV-visible and fluorescence spectra were noticed. The adsorption of carminic acid resulted in the formation of charge transfer complex with titania nanoparticles. This was confirmed by the electronic absorption and fluorescence emission spectroscopies. Chemisorption of porphyrin on the carminic acid functionalized titania further boosted the charge transfer effect. This was noticed by the increase in intensity and width of the charge transfer absorption and emission bands. Energy level diagram showed that the interaction among the constituents of the nano-hybrid assembly permitted the flow of electron in a cascade manner from carminic acid to TiO2.This also allowed direct flow of electrons either from carminic acid or porphyrin toward titania. The material was used as an active blend in hybrid bulk heterojunction solar cells. Co functionalized TiO2-based devices were found 3.5 times more efficient than the reference device but morphology of the device proved a major setback. PMID- 26555644 TI - Bench-scale evaluation of water disinfection by visible-to-UVC upconversion under high-intensity irradiation. AB - The feasibility of applying visible-to-UVC upconversion (UC) luminescence to enhance the kinetics of solar water disinfection was evaluated using Lu7O5F9:Pr(3+) ceramics incorporated into a solar reactor containing E. coli suspensions. Inactivation was assessed in batch conditions using both laser and lens-concentrated sunlight excitation conditions. Under 840-mW argon laser excitation, the UC efficiency was estimated to be 1 order of magnitude greater than previously reported under lamp excitation and UVC emitted by the reactors resulted in 3.6-log inactivation in 20 min. However, experiments using ~1500 mW of concentrated natural sunlight showed no additional inactivation that could be attributed to UC within the timescale studied. Due to the fundamental and practical limitations of solar focusing, the optical concentration ratio employed herein prevented the excitation beam from achieving the power densities required to attain UC efficiencies comparable to the laser experiments. We also observed that the high intensity of both the laser and sunlight induced rapid photoreactivation by the bacteria, which detracted from net disinfection performance. The results suggest that current UC materials perform inadequately for environmental application; nonetheless, valuable qualitative and quantitative insight was gained that more explicitly defines materials development goals and considerations for application of UC to environmental technology. PMID- 26555646 TI - Fourier Transform Raman and Statistical Analysis of Thermally Altered Samples of Amber. AB - We report the experimental results that refer to a Fourier transform Raman (FT Raman) survey of thermally altered Baltic and Romanian amber and the related statistical interpretation of data using principal component analysis (PCA). Although FT-Raman spectra show several small changes in the characteristic features of the investigated amber samples which may be used for discrimination, their visual recognition is relatively difficult, especially when interpreting data from archeological samples, and thus multivariate data analysis may be the solution to more accurately assign the geological origin based on overall characteristic spectral features. The two categories of amber have different behavior in terms of degradation during the experimental alteration, and Romanian amber is more susceptible to physico-chemical transformations by the aggressive environment when compared with Baltic amber. The obtained data were in accordance with the Fourier transform infrared (FT-IR) remarks published previously in a dedicated journal. The Raman technique is an alternative method that requires little to no sample preparation, water does not cause interference, and the spectra can be collected from a small volume (1-50 MUm in diameter). PMID- 26555645 TI - Mutation screening of SCN2A in schizophrenia and identification of a novel loss of-function mutation. AB - OBJECTIVES: There is a growing body of evidence suggesting a shared genetic susceptibility between many neuropsychiatric disorders, including schizophrenia, autism, intellectual disability (ID) and epilepsy. The sodium channel, voltage gated type II alpha subunit gene SCN2A has been shown to exhibit loss-of-function (LoF) mutations in individuals with seizure disorders, ID, autism and schizophrenia. The role of LoF mutations in schizophrenia is still uncertain with only one such mutation identified to date. METHODS: To seek additional evidence for a role for LoF mutations at SCN2A in schizophrenia we performed mutation screening of the entire coding sequence in 980 schizophrenia cases. Given an absence of LoF mutations in a public exome cohort (ESP6500, N=6503), we did not additionally sequence controls. RESULTS: We identified a novel, nonsense (i.e. stop codon) mutation in one case (E169X) that is absent in 4300 European-American and 2203 African-American individuals from the NHLBI Exome Sequencing Project. This is the second LoF allele identified in a schizophrenia case to date. We also show a novel, missense variant, V1282F, that occurs in two cases and is absent in the control dataset. CONCLUSION: We argue that very rare, LoF mutations at SCN2A act in a moderately penetrant manner to increase the risk of developing several neuropsychiatric disorders including seizure disorders, ID, autism and schizophrenia. PMID- 26555647 TI - Depletion of regulatory T-cells leads to moderate B-cell antigenicity in respiratory syncytial virus infection. AB - OBJECTIVES: The regulation of the immunopathology of respiratory syncytial virus (RSV) by regulatory T-cells (CD4(+)CD25(+)Foxp3(+); Tregs) is not understood. METHODS: To deduce the same, Tregs were depleted in BALB/c mice by injecting anti CD25 antibody followed by RSV infection (anti-CD25-RSV mice). RESULTS: In this model, a decrease in anti-fusion (F) antibody and neutralizing activity, and an increase in anti-nucleocapsid (N) antibody in serum, were seen. Decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activity, increased IgG2a, and an influx of activated CD8(+) T-cells into the lungs were also observed. Co culture of splenic CD45RA(+) B-cells from RSV-infected normal mice with CD4(+) cells isolated from anti-CD25-RSV mice (B/CD4) increased anti-F antibody secretion. The inclusion of CD25(+) Tregs isolated from isotype Ig-RSV mice into the B/CD4 co-culture substantially enhanced the frequency of anti-F antibody production. However, the same effect was not seen in the co-culture of CD45RA(+) B-cells with dendritic cells (DCs) (B/DCs) or CD8(+) cells (B/CD8) that were obtained from anti-CD25-RSV mice. The transfer of enriched B-cells from anti-CD25 RSV mice into RSV-infected SCID mice increased severe lung inflammation associated with the increased viral load and eosinophil number. CONCLUSIONS: These results indicate that Tregs modulate B-cell activity, particularly in producing F-specific neutralizing antibodies, to regulate RSV-mediated exacerbated diseases. PMID- 26555649 TI - Genotypic assessment of drug-resistant tuberculosis in Baghdad and other Iraqi provinces using low-cost and low-density DNA microarrays. AB - We report on a molecular investigation carried out to ascertain the prevalence of drug-resistant tuberculosis (TB) and the specific gene mutations responsible for resistance to rifampicin (RIF) and/or isoniazid (INH) in Iraq. In total, 110 clinical isolates from category II TB cases from Baghdad (58%) and several Iraqi provinces (42%) were analysed using colorimetric, low-cost and low-density (LCD) microarrays (MYCO-Direct and MYCO-Resist LCD array kits) to identify the point mutations responsible for resistance in Mycobacterium tuberculosis isolates. We found 76 patients (69.1%) had resistant strains, of which 40 (36%) were multidrug resistant (MDR)-TB. Where mono-resistance was identified, it was found to be predominantly to RIF (83%). The most common mutations were rpoB S531L (50%), inhA C15T (25%) and katG S315T (15%). The most common MDR-TB genotypes were rpoB S531L with inhA C15T (60%) and rpoB S531L with katG S315T (20%). Where phenotypic analysis of clinical isolates was also performed, genotypic data were found to show excellent correlation with phenotypic results. Correlation was found between the MYCO-Resist LCD array and GenoType MTBDRplus for detection of resistance to RIF. Our study shows MDR-TB in 36% of category II TB cases in Baghdad and surrounding Iraqi provinces, which reflects the World Health Organization findings based on phenotypic studies. Diagnosis of TB and MDR-TB using culture based tests is a significant impediment to global TB control. The LCD arrays investigated herein are easy to use, sensitive and specific molecular tools for TB resistance profiling in resource-limited laboratory settings. PMID- 26555648 TI - Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains. AB - BACKGROUND: Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. METHODS: A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe(-/-)) strains, was started on a Western diet at 6 weeks of age and maintained on the diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after 12 weeks of Western diet. 144 genetic markers across the entire genome were used for quantitative trait locus (QTL) analysis. RESULTS: One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was replicated at both time points and named Bglu16. Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice on either chow or Western diet. A significant correlation between fasting glucose and triglyceride levels was also observed on the Western diet. Haplotype analysis revealed that "lipid genes" Sik3, Apoa1, and Apoc3 were probable candidates for Bglu17. CONCLUSIONS: We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential candidate genes demonstrate genetic connections between dyslipidemia and type 2 diabetes. PMID- 26555650 TI - Statistical facilitation and the redundant signals effect: What are race and coactivation models? AB - As a supplement to Gondan and Minakata's (2015) tutorial on methods for testing the race model inequality, this theoretical note attempts to clarify further (a) the types of models that obey and violate the inequality and (b) the conclusions that can be drawn when the inequality is violated. In particular, the idea that individual racers proceed at the same speed in the single and redundant conditions (also known as "context independence") is shown to be better understood as an inherent part of Raab's (1962) original race model than as a separate, additional assumption. Thus, evidence that individual racers proceeded at different speeds in the single and redundant conditions, if available, should be viewed as supporting one type of coactivation model rather than an alternative model. In addition, it is shown that a class of race-like models without the assumption of context independence is so broad that it can never be falsified. PMID- 26555651 TI - No causal link between changes in hand position sense and feeling of limb ownership in the rubber hand illusion. AB - The rubber hand illusion is a perceptual illusion in which participants experience an inanimate rubber hand as belonging to their own body. The illusion is elicited by synchronously stroking the rubber hand and the participant's real hand, which is hidden from sight. The feeling of owning the rubber hand is accompanied by changes in hand position sense (proprioception), so that when participants are asked to indicate the location of their (unseen) hand, they indicate that it is located closer to the rubber hand. This "proprioceptive drift" is the most widely used objective measure of the rubber hand illusion, and from a theoretical perspective, it suggests a close link between proprioception and the feeling of body ownership. However, the critical question of whether a causal relationship exists between changes in hand position sense and changes in limb ownership is unknown. Here we addressed this question by devising a novel setup that allowed us to mechanically manipulate the position of the participant's hand without the participant noticing, while the rubber hand illusion was being elicited. Our results showed that changing the sensed position closer to or farther away from the rubber hand did not change the strength of the rubber hand illusion. Thus, the illusion is not dependent on changes in hand position sense. This finding supports models of body ownership and central body representation that hold that proprioceptive drift and the subjective illusion are related to different central processes. PMID- 26555652 TI - Pitching people with an inversion table: Estimates of body orientation are tipped as much as those of visual surfaces. AB - In the current work we investigate people's perception of their own body tilt in the pitch direction. In Experiment 1, we tilted people backward at 1 of 5 different randomly assigned angles using an inversion table. People significantly overestimated the angle at which they were tilted backward at angles from 8 degrees to 45 degrees . The slope of the plotted average overestimates had a gain of 1.46, fitting nicely with previously reported gains of verbal overestimates of visually perceived slant of natural outdoor geographically oriented slopes as well as man-made wooden slopes within and outside of reach in the laboratory. In Experiment 2, we showed participants a 45 degrees line and asked them to indicate when they were positioned at that orientation. Participants again significantly overestimated the angle at which they were tilted backward. This extends work showing that a scale-expanded theory of visual space is multisensory, results in equivalent estimates for both verbal and nonverbal/nonnumeric methods, and can now be expanded to include the perceived orientation of one's own body. PMID- 26555653 TI - An Efficient Labelling Approach to Harness Backbone and Side-Chain Protons in (1) H-Detected Solid-State NMR Spectroscopy. AB - (1) H-detection can greatly improve spectral sensitivity in biological solid state NMR (ssNMR), thus allowing the study of larger and more complex proteins. However, the general requirement to perdeuterate proteins critically curtails the potential of (1) H-detection by the loss of aliphatic side-chain protons, which are important probes for protein structure and function. Introduced herein is a labelling scheme for (1) H-detected ssNMR, and it gives high quality spectra for both side-chain and backbone protons, and allows quantitative assignments and aids in probing interresidual contacts. Excellent (1) H resolution in membrane proteins is obtained, the topology and dynamics of an ion channel were studied. This labelling scheme will open new avenues for the study of challenging proteins by ssNMR. PMID- 26555654 TI - One stage surgical treatment of aortic valve disease and aortic coarctation with aortic bypass grafting through the diaphragm and aortic valve replacement. AB - OBJECTIVES: To validate ascending aorta-lower abdominal aorta bypass grafting treatment for patients with descending aortic coarctation and an aortic valve disease. METHODS: The three patients in whom a descending atypical aortic coarctation was associated with an aortic valve disease were treated with one stage surgical treatment with aortic bypass grafting through the diaphragm and aortic valve replacement in our heart center. Operative technique consisted of performing ascending aorta-lower abdominal aorta bypass grafting through diaphragm muscle and implementing aortic valve replacement. The mean time for extracorporeal circulation and occluding clamp of aorta was recorded. Blood pressure data for pre- and post-operation was measured in the limbs. Computer enhanced transvenous angiograms of pre- and post-operation were applied for detection of aortic stenosis. The other adverse events were noticed in outpatient service during a follow-up period. RESULTS: The mean extracorporeal circulation time was 54 +/- 11 min. The mean time for occluding clamp of aorta was 34 +/- 6 min. An arterial pressure gradient was totally corrected after surgical treatment. Post-operation computer-enhanced transvenous angiograms showed the grafts to be open with a fluent flow. The patients had no gastrointestinal tract complications. No adverse event was noticed during a follow-up period in outpatient service. CONCLUSIONS: Treatment of ascending aorta-lower abdominal aorta bypass is advisable for patients with descending aortic coarctation and an aortic valve disease. PMID- 26555656 TI - [Not Available]. PMID- 26555655 TI - Impact of Treatment With Biologic Agents on the Use of Mechanical Devices Among Rheumatoid Arthritis Patients in a Large US Patient Registry. AB - OBJECTIVE: To assess trends and predictors of mechanical devices/aids use by rheumatoid arthritis (RA) patients since the introduction of biologic disease modifying antirheumatic drugs (DMARDs). METHODS: Sociodemographic characteristics, disease characteristics, and mechanical aid use (assessed using the Health Assessment Questionnaire) were compared among RA patients ages >17 years at diagnosis, enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry during January 2001 to December 2003 and January 2010 to December 2012. Univariate and multivariate logistic regression analyses were used to identify predictors of mechanical aid use among patients in both cohorts. RESULTS: Sociodemographic characteristics were similar between 1,096 patients in the 2001-2003 cohort and 11,140 patients in the 2010-2012 cohort. Disease activity was significantly lower among patients in the 2010-2012 cohort (mean +/- SD Clinical Disease Activity Index score 10.1 +/- 11.1 versus 17.0 +/- 13.8; P < 0.001). A greater proportion of patients in the 2010-2012 cohort received biologic DMARDs (50.7% versus 32.5%; P < 0.001) and fewer were biologic naive (39.1% versus 61.6%; P < 0.001). Fewer patients in the 2010-2012 cohort used any mechanical devices/aids (31.1% versus 40.8%; P < 0.001). In multivariate analysis, patients in the 2010-2012 cohort and those with a history of biologic agent use were less likely to use devices/aids (odds ratio [OR] 0.77 [95% confidence interval (95% CI) 0.66-0.90] and OR 0.68 [95% CI 0.62-0.75], respectively). Predictors of greater devices/aids usage included older age, female sex, higher disease activity, and less employment. Effect sizes were greatest for disease activity and employment. CONCLUSION: Mechanical devices/aids use among patients with RA was significantly lower during 2010-2012 versus 2001 2003 and among biologic-experienced patients, suggesting reduced disability. PMID- 26555657 TI - [The "JOINT specialist training scholarship" of the German Society for Rheumatology foundation: A success story]. PMID- 26555658 TI - [Conservative local therapy of rheumatological diseases]. PMID- 26555659 TI - [Indications and contraindications for radiosynoviorthesis]. AB - BACKGROUND: Radiosynoviorthesis (RSO) provides a simple method for the treatment of patients with chronic synovitis and has only few side effects. OBJECTIVES: Evidence-based indications and contraindications for performing RSO based on the current literature are presented. MATERIAL AND METHODS: Published information on the indications and contraindications for performing RSO in chronic synovitis were analyzed and summarized. RESULTS: According to the guideline recommendations of the German Society of Rheumatology indications for RSO are given in patients with rheumatoid arthritis, seronegative spondyloarthropathy, crystal arthropathy, villonodular synovitis and hemophilia with recurrent joint bleeding. Osteoarthritis with documented reactive synovitis is also regarded as an indication in the guidelines of the nuclear medicine societies. The European League Against Rheumatism (EULAR) and the German Society of Rheumatology (DGRh) have given no recommendations for using RSO in osteoarthritis. Given the correct indications RSO shows high success rates. CONCLUSION: The effects of RSO with the named secondary side effects last on average for 5 years. Crucial for the success of RSO are the correct indications, the correct timing and combination with other therapeutic procedures, such as surgical synovectomy. PMID- 26555660 TI - [Operative treatment of the rheumatic shoulder]. AB - The duration and severity of rheumatic diseases of the shoulder correlate with symptom frequency, structural changes and associated functional limitations. The multifactorial character of the underlying rheumatic disease requires a multimodal therapeutic concept including interaction of surgical and non-surgical disciplines. In addition to basic systemic anti-inflammatory medication, injections targeting the synovial tissue by corticoid instillation and glenohumeral radiosynoviorthesis (with an intact rotator cuff) are further options. Operative interventions on rheumatic shoulders can be characterized as disease-modifying, protective, reconstructive or palliative, depending on the stage. Combining minimally invasive arthroscopic surgical techniques with modern basic therapy has the potential to shift the indications for operative interventions towards an earlier stage of disease without favoring or propagating structural alterations which have already occurred. In cases of severe joint destruction with loss of the rotator cuff, reverse shoulder arthroplasty can be an appropriate option. PMID- 26555663 TI - Stevens-Johnson syndrome and toxic epidermal necrolysis: an update on pharmacogenetics studies in drug-induced severe skin reaction. AB - Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life threatening drug reactions involving skin and membranes mucous, which are associated with significant morbidity and mortality and triggered, especially by drug exposure. Different studies have demonstrated that drug response is a multifactorial character and that the interindividual variability in this response depends on both environmental and genetic factors. The last ones have a relevant significance. In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice. PMID- 26555665 TI - Local, Controlled Delivery of Local Anesthetics In Vivo from Polymer - Xerogel Composites. AB - PURPOSE: Polymer-xerogel composite materials have been introduced to better optimize local anesthetics release kinetics for the pain management. In a previous study, it was shown that by adjusting various compositional and nano structural properties of both inorganic xerogels and polymers, zero-order release kinetics over 7 days can be achieved in vitro. In this study, in vitro release properties are confirmed in vivo using a model that tests for actual functionality of the released local anesthetics. METHODS: Composite materials made with tyrosine-polyethylene glycol(PEG)-derived poly(ether carbonate) copolymers and silica-based sol-gel (xerogel) were synthesized. The in vivo release from the composite controlled release materials was demonstrated by local anesthetics delivery in a rat incisional pain model. RESULTS: The tactile allodynia resulting from incision was significantly attenuated in rats receiving drug-containing composites compared with the control and sham groups for the duration during which natural healing had not yet taken place. The concentration of drug (bupivacaine) in blood is dose dependent and maintained stable up to 120 h post-surgery, the longest time point measured. CONCLUSIONS: These in vivo studies show that polymer-xerogel composite materials with controlled release properties represent a promising class of controlled release materials for pain management. PMID- 26555664 TI - Tetracyclines in malaria. AB - Malaria, a parasite vector-borne disease, is one of the greatest health threats in tropical regions, despite the availability of malaria chemoprophylaxis. The emergence and rapid extension of Plasmodium falciparum resistance to various anti malarial drugs has gradually limited the number of potential malaria therapeutics available to clinicians. In this context, doxycycline, a synthetically derived tetracycline, constitutes an interesting alternative for malaria treatment and prophylaxis. Doxycycline is a slow-acting blood schizontocidal agent that is highly effective at preventing malaria. In areas with chloroquine and multidrug resistant P. falciparum parasites, doxycycline has already been successfully used in combination with quinine to treat malaria, and it has been proven to be effective and well-tolerated. Although not recommended for pregnant women and children younger than 8 years of age, severe adverse effects are rarely reported. In addition, resistance to doxycycline is rarely described. Prophylactic and clinical failures of doxycycline have been associated with both inadequate doses and poor patient compliance. The effects of tetracyclines on parasites are not completely understood. A better comprehension of the mechanisms underlying drug resistance would facilitate the identification of molecular markers of resistance to predict and survey the emergence of resistance. PMID- 26555666 TI - Model-Based Optimisation of Deferoxamine Chelation Therapy. AB - PURPOSE: Here we show how a model-based approach may be used to provide further insight into the role of clinical and demographic covariates on the progression of iron overload. The therapeutic effect of deferoxamine is used to illustrate the application of disease modelling as a means to characterising treatment response in individual patients. METHODS: Serum ferritin, demographic characteristics and individual treatment data from clinical routine practice on 27 patients affected by beta-thalassaemia major were used for the purposes of this analysis. The time course of serum ferritin was described by a hierarchical nonlinear mixed effects model, in which compliance was parameterised as a covariate factor. Modelling and simulation procedures were implemented in NONMEM (7.2.0). RESULTS: A turnover model best described serum ferritin changes over time, with the effect of blood transfusions introduced on the ferritin conversion rate and the effect of deferoxamine on the elimination parameter (Kout) in a proportional manner. The results of the simulations showed that poor quality of execution is preferable over drug holidays; and that independently of the compliance pattern, the therapeutic intervention is not effective if >60% of the doses are missed. CONCLUSIONS: Modelling of ferritin response enables characterisation of the dynamics of iron overload due to chronic transfusion. The approach can be used to support decision making in clinical practice, including personalisation of the dose for existing and novel chelating agents. PMID- 26555667 TI - Correcting the Relative Bias of Light Obscuration and Flow Imaging Particle Counters. AB - PURPOSE: Industry and regulatory bodies desire more accurate methods for counting and characterizing particles. Measurements of proteinaceous-particle concentrations by light obscuration and flow imaging can differ by factors of ten or more. METHODS: We propose methods to correct the diameters reported by light obscuration and flow imaging instruments. For light obscuration, diameters were rescaled based on characterization of the refractive index of typical particles and a light scattering model for the extinction efficiency factor. The light obscuration models are applicable for either homogeneous materials (e.g., silicone oil) or for chemically homogeneous, but spatially non-uniform aggregates (e.g., protein aggregates). For flow imaging, the method relied on calibration of the instrument with silica beads suspended in water-glycerol mixtures. RESULTS: These methods were applied to a silicone-oil droplet suspension and four particle suspensions containing particles produced from heat stressed and agitated human serum albumin, agitated polyclonal immunoglobulin, and abraded ethylene tetrafluoroethylene polymer. All suspensions were measured by two flow imaging and one light obscuration apparatus. Prior to correction, results from the three instruments disagreed by a factor ranging from 3.1 to 48 in particle concentration over the size range from 2 to 20 MUm. Bias corrections reduced the disagreement from an average factor of 14 down to an average factor of 1.5. CONCLUSIONS: The methods presented show promise in reducing the relative bias between light obscuration and flow imaging. PMID- 26555668 TI - From palliative to curative treatment - stage IV mucinous adenocarcinoma, successfully treated with metronomic capecitabine in combination with Bevacizumab and surgery- a case report. AB - BACKGROUND: Mucinous adenocarcinoma (MAC) represents 6-19 % of all colorectal carcinoma. It is associated with poorer response to chemotherapy and chemoradiotherapy. CASE PRESENTATION: A 27-year-old Swedish woman presented with stomach pain and weight loss, and was diagnosed with locally advanced MAC in the transverse colon as well as 3 liver metastases. Neoadjuvant treatment with fluorouracil, folinic acid and oxaliplatin (FLOX) failed due to several infections, pulmonary embolism and deteriorated performance status. The patient was therefore considered palliative. Palliative treatment with metronomic capecitabine 500 mg * 2 daily and bevacizumab every other week were initiated. After 4 months of treatment the tumors had regressed and the patient was able to undergo radical surgery, thereby changing the treatment intention from palliative to curative. No adjuvant chemotherapy was given. There were no signs of recurrence 9 months later. CONCLUSIONS: The role of the combination of metronomic capecitabine and bevacizumab in patients with MAC merits further investigation. PMID- 26555669 TI - Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland. AB - SCOPE: We studied the impact of dietary supplementation with licorice root components on diet-induced obesity, fat accumulation, and hepatic steatosis in ovariectomized C57BL/6 mice as a menopause model. MATERIALS AND METHODS: We evaluated the molecular and physiological effects of dietary licorice root administered to ovariectomized C57BL/6 mice as root powder (LRP), extracts (LRE), or isolated isoliquiritigenin (ILQ) on reproductive (uterus and mammary gland) and nonreproductive tissues important in regulating metabolism (liver, perigonadal, perirenal, mesenteric, and subcutaneous fat). Quantitative outcome measures including body weight, fat distribution (magnetic resonance imaging), food consumption, bone density and weight (Dual-energy X-ray absorptiometry), and gene expression were assessed by the degree of restoration to the preovariectomized health state. We characterized histological (H&E and oil red O staining) and molecular properties (expression of certain disease markers) of these tissues, and correlated these with metabolic phenotype as well as blood levels of bioactives. CONCLUSION: Although LRE and ILQ provided some benefit, LRP was the most effective in reducing body weight gain, overall fat deposition, liver steatosis, and expression of hepatic lipid synthesis genes following ovariectomy. Our data demonstrate that licorice root provided improvement of multiple metabolic parameters under conditions of low estrogen and high-fat diets without stimulating reproductive tissues. PMID- 26555670 TI - Comparison of a traditional and non-traditional residential care facility for persons living with dementia and the impact of the environment on occupational engagement. AB - BACKGROUND: Dementia residential facilities can be described as traditional or non-traditional facilities. Non-traditional facilities aim to utilise principles of environmental design to create a milieu that supports persons experiencing cognitive decline. This study aimed to compare these two environments in rural Australia, and their influence on residents' occupational engagement. METHODS: The Residential Environment Impact Survey (REIS) was used and consists of: a walk through of the facility; activity observation; interviews with residents and employees. Thirteen residents were observed and four employees interviewed. Resident interviews did not occur given the population diagnosis of moderate to severe dementia. Descriptive data from the walk-through and activity observation were analysed for potential opportunities of occupational engagement. Interviews were thematically analysed to discern perception of occupational engagement of residents within their facility. RESULTS: Both facilities provided opportunities for occupational engagement. However, the non-traditional facility provided additional opportunities through employee interactions and features of the physical environment. Interviews revealed six themes: Comfortable environment; roles and responsibilities; getting to know the resident; more stimulation can elicit increased engagement; the home-like experience and environmental layout. These themes coupled with the features of the environment provided insight into the complexity of occupational engagement within this population. CONCLUSION: This study emphasises the influence of the physical and social environment on occupational engagement opportunities. A non-traditional dementia facility maximises these opportunities and can support development of best-practice guidelines within this population. PMID- 26555671 TI - Research and Evaluations of the Health Aspects of Disasters, Part III: Framework for the Temporal Phases of Disasters. AB - Each of the elements described in the Conceptual Framework for disasters has a temporal designation; each has a beginning and end time. The Temporal Framework defines these elements as phases that are based on characteristics rather than on absolute times. The six temporal phases include the: (1) Pre-event; (2) Event; (3) Structural Damage; (4) Functional Damage (changes in levels of functions of the Societal Systems); (5) Relief; and (6) Recovery phases. Development is not a phase of a disaster. The use of the Temporal Framework in studying and reporting disasters allows comparisons to be made between similar phases of different disasters, regardless of the hazard involved and/or the community impacted. For research and evaluation purposes, assessments, plans, and interventions must be described in relation to the appropriate temporal phase. PMID- 26555672 TI - Rmg8, a New Gene for Resistance to Triticum Isolates of Pyricularia oryzae in Hexaploid Wheat. AB - Blast, caused by Pyricularia oryzae, is one of the major diseases of wheat in South America. We identified a new gene for resistance to Triticum isolates of P. oryzae in common wheat 'S-615', and designated it "resistance to Magnaporthe grisea 8" (Rmg8). Rmg8 was assigned to chromosome 2B through molecular mapping with simple-sequence repeat markers. To identify an avirulence gene corresponding to Rmg8, Triticum isolate Br48 (avirulent on S-615) was crossed with 200R29 (virulent on S-615), an F1 progeny derived from a cross between an Eleusine isolate (MZ5-1-6) and Br48. Segregation analysis of their progeny revealed that avirulence of Br48 on S-615 was conditioned by a single gene, which was designated AVR-Rmg8. AVR-Rmg8 was closely linked to AVR-Rmg7, which corresponded to Rmg7 located on chromosome 2A of tetraploid wheat. PMID- 26555673 TI - Place and Response Learning in the Open-field Tower Maze. AB - This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how "stress" might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function(1). The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response learning in adult female Sprague Dawley rats(2). Future studies will be designed to examine the role of the hippocampus and striatum in place- and response learning in the OFTM. PMID- 26555674 TI - Compliance of psychotropic drug prescription with clinical practice guidelines in older inpatients. AB - Several practice guidelines were published by French regulatory agencies between 2006 and 2009 to improve psychotropic drug use in older patients. The objectives of the study were to assess compliance with these guidelines in older patients hospitalized in psychiatric units and to identify characteristics associated with compliance. A cross-sectional study was conducted in 117 patients aged 65 years and older hospitalized in two psychiatric departments of a public hospital, at three dates randomly chosen between January and May 2014. Medical and sociodemographic characteristics were collected from electronic medical records. In all, 8% of psychotropic prescriptions were compliant with guidelines. A total of 98% of antidepressant prescriptions complied with guidelines for product selection (no tricyclics) and 72% for initial dosage (half of that recommended for younger adults). Regarding benzodiazepines, short half-life drugs were chosen in 73% of treatments, low maintenance dosage was found in 64% of treatments, and a discontinuous administration rhythm was noted in 33% of treatments. Regarding antipsychotics, initial dosage was a quarter of the allowed initial dosage for younger adults in 39% of prescriptions and metabolic blood testing was performed in 17% of prescriptions. Neurological and cognitive tolerance was monitored in 41% and 61% of prescriptions, respectively. Few clinical factors were found to be associated with compliance or noncompliance with guidelines in older psychiatric inpatients. Practice guidelines on psychotropic drug prescription were partially respected in older inpatients. Practitioners should take into account the risks associated with non-recommended patterns of psychotropic drug use in this vulnerable population. PMID- 26555675 TI - Efficacy of Donepezil for Cognitive Impairments in Familial Hypercholesterolemia: Preclinical Proof of Concept. PMID- 26555676 TI - Solid-State Dynamic Nuclear Polarization at 9.4 and 18.8 T from 100 K to Room Temperature. AB - Efficient dynamic nuclear polarization (DNP) in solids, which enables very high sensitivity NMR experiments, is currently limited to temperatures of around 100 K and below. Here we show how by choosing an adequate solvent, (1)H cross effect DNP enhancements of over 80 can be obtained at 240 K. To achieve this we use the biradical TEKPol dissolved in a glassy phase of ortho-terphenyl (OTP). We study the solvent DNP enhancement of both TEKPol and BDPA in OTP in the range from 100 to 300 K at 9.4 and 18.8 T. Surprisingly, we find that the DNP enhancement decreases only relatively slowly for temperatures below the glass transition of OTP (Tg = 243 K), and (1)H enhancements around 15-20 at ambient temperature can be observed. We use this to monitor molecular dynamic transitions in the pharmaceutically relevant solids Ambroxol and Ibuprofen. PMID- 26555678 TI - Correction: Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model. PMID- 26555677 TI - Varicella seroprevalence in healthcare workers in a tertiary hospital: an audit of cross-sectional data. AB - BACKGROUND: The seroprevalence of varicella in Southeast Asia is not well described especially in healthcare workers (HCW) in the region. We report the varicella seroprevalence among healthcare workers from a diverse range of countries working in a tertiary care hospital in Singapore. METHODS: We audited the results of annual HCW health screening, which included a varicella assay, from the years 2009 to 2014. During this period, there was a change in hospital policy mandating varicella immunity for all newly employed healthcare workers. The serological data were reviewed with employment records on occupation and nationality. Seroprevalence rates were determined by standard commercial enzyme linked immunosorbent assays for each year of testing. Odds of being immune in 2014 were compared by means of multiple logistic regression. RESULTS: A total of 10,585 samples were obtained from 6668 unique individuals over four separate cross-sections of the hospital workforce. A peak seroprevalence of 92.8 % (95 % CI 92.0-93.5) was recorded in 2014. Younger employees had a lower seroprevalence than their older colleagues. In a consolidated sample of 4875 members of the active workforce in October 2014, we identified that Indian nationals were less likely to be immune than their Singaporean national colleagues, odds ratio (OR) 0.26 (95 % CI 0.17-0.43, p < 0.001), while Chinese nationals were more likely to be immune, OR 4.34 (95 % CI 1.61-12.2, p = 0.004), after controlling for year of screening, gender, age-group and vocation. In 2014, being employed as administrative staff, OR 0.43 (95 % CI 0.29-0.64, p < 0.001) or contract service provider, OR 0.30 (95 % CI 0.19-0.47, p < 0.001), was also associated with a lower odds of being immune than being employed as a nurse. CONCLUSIONS: There remain a small number of healthcare workers who are non-immune to varicella in our tertiary hospital. A new pre-employment policy of mandatory screening and vaccination may have increased rates of immunity but more needs to be done to ensure that all of our employees are immune to varicella to protect our vulnerable patients. PMID- 26555679 TI - Organocatalytic 1,4-Addition Reaction of 2-Formyl(thio)esters to Vinylketones: An Efficient Access to Acyclic Chiral Building Blocks with a Quaternary Carbon Stereocenter. AB - 2-Formyl(thio)esters were utilized as pronucleophiles to obtain less-accessible acyclic chiral building blocks bearing versatile functional groups on a quaternary carbon atom for enantioselective 1,4-addition to vinylketones. To achieve high enantioselectivity in the present 1,4-addition reaction, thiourea tertiary amines containing a bulky chiral backbone were developed as catalysts, and several derivatizations of the products were performed to demonstrate the synthetic utility of the products. PMID- 26555680 TI - The fat mass and obesity-associated (FTO) gene variant rs9939609 predicts long term incidence of cardiovascular disease and related death independent of the traditional risk factors. AB - OBJECTIVE AND METHODS: The impact of the rs9939609 FTO variant on cardiovascular events was investigated in the 19-year follow-up of subjects recruited to the OPERA study. RESULTS: A total of 212 cardiovascular disease (CVD) and 152 coronary heart disease (CHD) events or deaths occurred during follow-up. The logistic regression analysis revealed that among the AA genotype the incidence of CHD (OR 1.905; 95% CI 1.250-2.903, p = 0.001) and CVD (OR 1.849; 1.265-2.702, p = 0.003) events or death was significantly higher when adjusted for age, sex, and study group. After further adjustment with BMI, smoking status, systolic blood pressure, and low-density lipoprotein cholesterol, the higher incidence of CHD and CVD events or death among subjects with the AA genotype remained significant (OR 1.895; p = 0.002 and p = 0.004, respectively). In Cox regression analysis, the AA genotype displayed a higher rate of CVD and CHD death when the model was adjusted for sex, age, and study group (p = 0.006 and p = 0.046). FTO rs9939609 AA genotype improved the C-index of the final predictive model from 0.709 to 0.715. In reclassification analyses, the integrated discrimination index was significant 0.011 (p = 0.010). CONCLUSION: The AA genotype of FTO rs9939609 seems to be associated with a higher risk of CVD, and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis. PMID- 26555681 TI - Association of interleukin-1 receptor antagonist VNTR polymorphism and risk of pre-eclampsia in southeast Iranian population. AB - AIM: Pre-eclampsia (PE) is an obstetric disorder that may result in maternal and neonatal mortality and morbidity. Growing evidence indicates that cytokines, such as interleukins, are involved in the pathogenesis of this complication. Hence the current study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and PE susceptibility in southeast Iranian women. MATERIAL AND METHODS: The IL-Ra VNTR polymorphism was evaluated in 192 PE women and 186 age-matched normotensive pregnant women by the polymerase chain reaction method. RESULTS: The frequency of the A2 allele and the A2A2 genotype of IL-Ra VNTR polymorphism was significantly lower in PE patients compared to controls: therefore, A2 allele may play a protective role in PE development (odds ratio = 0.13 95% CI, [0.04-0.03]; P < 0.0001). In addition, there was no relation between the IL-Ra VNTR polymorphism and severity of the disease. CONCLUSION: The A2 allele of the IL-Ra VNTR polymorphism could be a protective factor for PE susceptibility. PMID- 26555682 TI - Commentary on Zvonareva et al. PMID- 26555683 TI - FRET-Based Probe for Monitoring pH Changes in Lipid-Dense Region of Hct116 Cells. AB - A rhodamine conjugate (L) with a pseudo Stokes shift of 165 nm is used for probing changes in solution pH under physiological conditions. This reagent is found to be nontoxic, and the luminescence response could be used for imaging changes in endogenous pH induced by dexamethanose (DMT) in the endoplasmic reticulum. PMID- 26555684 TI - Drosophila domino Exhibits Genetic Interactions with a Wide Spectrum of Chromatin Protein-Encoding Loci. AB - The Drosophila domino gene encodes protein of the SWI2/SNF2 family that has widespread roles in transcription, replication, recombination and DNA repair. Here, the potential relationship of Domino protein to other chromatin-associated proteins has been investigated through a genetic interaction analysis. We scored for genetic modification of a domino wing margin phenotype through coexpression of RNAi directed against a set of previously characterized and more newly characterized chromatin-encoding loci. A set of other SWI2/SNF2 loci were also assayed for interaction with domino. Our results show that the majority of tested loci exhibit synergistic enhancement or suppression of the domino wing phenotype. Therefore, depression in domino function sensitizes the wing margin to alterations in the activity of numerous chromatin components. In several cases the genetic interactions are associated with changes in the level of cell death measured across the dorsal-ventral margin of the wing imaginal disc. These results highlight the broad realms of action of many chromatin proteins and suggest significant overlap with Domino function in fundamental cell processes, including cell proliferation, cell death and cell signaling. PMID- 26555685 TI - A New Way to Estimate the Potential Unmet Need for Infertility Services Among Women in the United States. AB - BACKGROUND: Fewer than 50% of women who meet the medical/behavioral criteria for infertility receive medical services. Estimating the number of women who both meet the medical/behavioral criteria for infertility and who have pro-conception attitudes will allow for better estimates of the potential need and unmet need for infertility services in the United States. METHODS: The National Survey of Fertility Barriers was administered by telephone to a probability sample of 4,712 women in the United States. The sample for this analysis was 292 women who reported an experience of infertility within 3 years of the time of the interview. Infertile women were asked if they were trying to conceive at the time of their infertility experience and if they wanted to have a child to determine who could be considered in need of services. RESULTS: Among U.S. women who have met medical criteria for infertility within the past three years, 15.9% report that they were neither trying to have a child nor wanted to have a child and can be classified as not in need of treatment. Of the 84.9% of infertile women in need of treatment, 58.1% did not even talk to a doctor about ways to become pregnant. DISCUSSION: Even after taking into account that not all infertile women are in need of treatment, there is still a large unmet need for infertility treatment in the United States. CONCLUSION: Studies of the incidence of infertility should include measures of both trying to have a child and wanting to have a child. PMID- 26555686 TI - Pathophysiological aspects of ureterorenoscopic management of upper urinary tract calculi. AB - PURPOSE OF REVIEW: Indications for ureterorenoscopy are expanding without hard scientific evidence to support its efficacy. Therefore, it is extremely important to focus on potential harmful effects of the procedure itself. This review explores how physiology of the upper urinary tract reacts to ureterorenoscopy, potentially translating into harmful effects, and how such pathophysiological processes may be minimized. RECENT FINDINGS: Complications to ureterorenoscopy and postoperative pain seem to be related to intrarenal pressure and/or access. Mean intrarenal pressures in the range of 60-100 mmHg during ureterorenoscopy without access sheaths have been measured, thus by far exceeding the threshold for intrarenal backflow, potentially resulting in septic complications. Intrarenal pressure may be reduced by use of ureteral access sheaths, which, however, may cause ureteral damage due to the limited size of the ureter and strain-induced ureteral contractions (peristalsis). Different receptor types modulate this peristaltic activity. beta-receptor agonists have been investigated in animal and human trials for the purpose of relaxing the ureter. In randomized, placebo-controlled trials in pigs and humans, usage of the beta-receptor agonist isoproterenol in the irrigation fluid has shown a potential for reducing both intrarenal pressure and ureteral tone during ureterorenoscopy. SUMMARY: Upper urinary tract physiology has unique features that may be pushed into pathophysiological processes by the unique elements of ureterorenoscopy: access and irrigation. Pharmacological ureteral relaxation during ureterorenoscopy deserves further attention with regard to reducing complications and postoperative pain. PMID- 26555687 TI - Complications of percutaneous nephrolithotomy: classification, management, and prevention. AB - PURPOSE OF REVIEW: Percutaneous nephrolithotomy (PCNL) provides the highest stone free rate after one session and low morbidity rates in cases of large or multiple renal calculi. The classification, management, and prevention of complications of PCNL are reviewed. RECENT FINDINGS: PCNL is a well tolerated and very effective procedure for the management of renal stones. Specific complications limit the surgical outcome of PCNL whereas the majority of the complications are resolving with conservative or minimally invasive management. Experience with the technique is important for minimizing complications. There is an ongoing effort to classify the complications and to achieve a consensus in reporting the complications and surgical outcome of the procedure. SUMMARY: The knowledge of risk factors, complications, and their management is important for every endourologist. Establishing of a PCNL-specific classification system for reporting outcomes and complications could set the basis for further improvement of the PCNL technique and outcomes. PMID- 26555688 TI - Benefits and risks of ureteral access sheaths for retrograde renal access. AB - PURPOSE OF REVIEW: Ureteral access sheath (UAS) became increasingly popular worldwide. However, the safety of its routine use remains controversial. The aim of the current revision is to provide a systematic review on the benefits and disadvantages of the UAS. RECENT FINDINGS: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Two reviewers independently searched the literature, finally identifying 20 articles valuable for this review. The use of UAS demonstrated several advantages to facilitate retrograde intrarenal access, lower intrarenal pressure, protect the ureter, protect the scope, and expedite stone extraction. Despite this, there is also some evidence that UAS use may be associated with acute ureteral injury and long-term complications, apparently related to maneuvers for UAS insertion and mucosal or deeper layers of injury and ischemia. Furthermore, there are still pending questions on the possible increase in stone free rates, and decrease in operative time and costs. SUMMARY: Although the use of UAS is associated with some risk and limiting factors, it appears from this systematic review that its use is common and safe for the retrograde intrarenal access. Therefore, UAS is highly recommended for the treatment of upper tract disease by means of retrograde intrarenal surgery. PMID- 26555689 TI - Positioning for percutaneous nephrolithotomy. AB - PURPOSE OF THE REVIEW: To highlight the progressive evolution of the issue of patient positioning for percutaneous nephrolithotomy (PNL), explain the history of the prone and supine positions, report respective advantages and drawbacks, critically interpret the past and current literature supporting such arguments, identify the best candidates for each position, and reflect on the future evolution of the two approaches. RECENT FINDINGS: Positioning for PNL has become a matter of debate during the last decade. The traditional prone PNL position - most widely performed with good success and few complications, and exhibiting essentially no limits except for the treatment of pelvic kidneys - is nowadays flanked mainly by the supine and supine-modified positions, equally effective and probably safer from an anesthesiological point of view. Of course, both approaches have a number of advantages and drawbacks, accurately reported and critically sieved. SUMMARY: The current challenge for endourologists is to be able to perform PNL in both prone and supine positions to perfectly tailor the procedure on any patient with any stone burden, including increasingly challenging cases and medically high-risk patients, according to the patient's best interest. Intensive training and experience is especially needed for supine PNL, still less popular and underperformed worldwide. VIDEO ABSTRACT: http://links.lww.com/COU/A8. PMID- 26555690 TI - Imaging for urolithiasis: standards, trends, and radiation exposure. AB - PURPOSE OF REVIEW: To discuss current trends in imaging for urolithiasis and review the recent scientific literature surrounding this topic. Specifically, to address the efforts urologist should be making to reduce the use of ionizing radiation and to examine alternatives to computerized tomography (CT) scan in diagnosing and managing patients with stones. RECENT FINDINGS: Although CT remains the gold standard for diagnosing urolithiasis, low-dose and ultralow-dose CT scans should be utilized more frequently. Imaging with ultrasound and digital tomosynthesis, especially in follow-up for urolithiasis, offers the dual benefit of reduced patient radiation exposure and acceptable diagnostic ability. SUMMARY: Urolithiasis is a prevalent and recurrent condition and patient radiation exposure throughout diagnosis and management of this disease needs to be considered. Imaging modalities that limit radiation and preserve diagnostic accuracy must be utilized. PMID- 26555691 TI - Long-term follow-up data more than 5 years after surgical management of benign prostate obstruction: who stands the test of time? AB - PURPOSE OF REVIEW: Surgical techniques are an integral part of the urologist's armamentarium for the treatment of benign prostatic obstruction. Currently, several techniques are available. The purpose of the current review is to analyse the long-term outcomes of currently available techniques. RECENT FINDINGS: Open prostatectomy shows a low long-term reoperation rate. Available evidence suggests that bipolar transurethral resection of the prostate (TURP) is an attractive alternative to monopolar TURP as both techniques lead to a long-lasting and comparable efficacy. For patients with a larger prostate volume, bipolar enucleation of the prostate appears as safe and effective alternative to open prostatectomy. Holmium laser enucleation of the prostate appears as a durable alternative to TURP and open prostatectomy with comparable long-term results. For photoselective vaporization of the prostate, differently powered models are available. Currently, only long-term data with lower powered 80 W laser are available, reporting reoperation rates higher than those reported from other surgical techniques. On the thulium laser, currently only one study reported 5 year results and despite encouraging results further confirmation seems necessary. SUMMARY: Various surgical methods have proven to be safe and effective for the treatment of benign prostate obstruction and stand the test of time. The choice of the technique depends on prostate size, risk factors of the patient as well as expertise of the surgeon. PMID- 26555692 TI - Undiagnosed neurological disease as a potential cause of male lower urinary tract symptoms. AB - PURPOSE OF REVIEW: In the central nervous system there are many regulatory processes controlling the lower urinary tract. This review considers the possibility that urinary dysfunction may precede diagnosis of neurological disease. RECENT FINDINGS: Lower urinary tract symptoms (LUTS) occur early in multiple system atrophy, Parkinson's disease and normal pressure hydrocephalus, and may present before neurological diagnosis. Some people present with LUTS and subsequently are diagnosed with multiple sclerosis or a spinal condition. In male LUTS, the symptoms could reflect early stages of a neurological disease, which has not yet been diagnosed ('occult neurology'). Key symptoms include erectile dysfunction, retrograde ejaculation, enuresis, loss of filling sensation or unexplained stress urinary incontinence. Directed questioning should enquire about visual symptoms, back pain, anosmia, bowel dysfunction and incontinence, or memory loss. Examination features can include resting tremor, 'croaky' speech, abnormal gait, orthostatic hypotension, ataxia, or altered perineal sensation. Imaging, such as MRI scan, should only be requested after expert neurological examination, to ensure the correct parts of the central nervous system are scanned with appropriate radiological protocols. SUMMARY: Urologists should consider an undiagnosed neurological condition can be present in a few cases. Any finding should be further evaluated by colleagues with relevant expertise. PMID- 26555693 TI - Preservation of sexual function when relieving benign prostatic obstruction surgically: can a trade-off be considered? AB - PURPOSE OF REVIEW: There is increasing interest among men who require benign prostatic obstruction (BPO) surgery for treatment, which also preserves sexual function. Transurethral resection of the prostate (TURP) impacts sexual function; some novel treatments claim to preserve it. Concerns exist among urologists however: can sexual function truly be preserved whilst achieving the same magnitude and durability of lower urinary tract symptoms (LUTS) improvement? Can a trade-off be considered? This review examines the literature over the recent 12 18 months to determine whether surgical BPO treatments can truly preserve sexual function whilst effectively treating LUTS-BPO. RECENT FINDINGS: TURP negatively impacts erectile function, but laser prostatectomy does not. Established cavitating BPO surgeries (TURP and laser prostatectomy) tend to have high rates of an ejaculation. Ejaculation sparing modifications to existing cavitating surgeries show promising outcomes in early reports. Prostatic urethral lift preserves ejaculatory and erectile function, whilst significantly improving LUTS in short to medium-term follow-up. WAVE (Rezum System) appears promising for LUTS treatment whilst preserving sexual function in early studies. SUMMARY: Pathophysiological mechanisms underlying the association between LUTS-BPO and sexual function are not entirely understood. Whilst novel procedures can preserve both antegrade ejaculation and erectile function, long-term efficacy in maintaining benefits to LUTS is to be established. Although standard cavitating surgeries are associated with significant anejaculation, new modifications to surgical technique may offer promising solutions. PMID- 26555694 TI - Multiparametric ultrasound in the diagnosis of prostate cancer. AB - PURPOSE OF REVIEW: A summary and analysis of the current evidence on the role of multiparametric ultrasound in the diagnosis of clinically significant prostate cancer. RECENT FINDINGS: Earlier work on brightness-mode or Doppler ultrasound did not reveal an adequate diagnostic performance but the addition of contrast enhanced ultrasound and elastography shows greater promise. There has been an increase in trials on contrast-enhanced ultrasound of late, with and without the use of quantification, such as parametric mapping of contrast uptake. Shear wave elastography offers quantification for this modality also and early work is available on the kilopascal thresholds that may be significant for malignancy. Perhaps the most promising avenue is the combination of the above modalities but to date only one study has considered this. SUMMARY: Although there is a paucity of high-quality studies at present, particularly those that combine all the available ultrasound modalities, the performance of ultrasound is seen to approach that of multiparametric MRI in some cases. More work is needed to define a role, if any, for ultrasound in the diagnosis of prostate cancer. PMID- 26555695 TI - Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo. AB - Interleukin-6 (IL-6) is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman's Disease (CD) and rheumatoid arthritis (RA). Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R)/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs) directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs) directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK) profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG) moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA) and C-reactive protein (CRP). This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology. PMID- 26555696 TI - Odorous secretions in anurans: morphological and functional assessment of serous glands as a source of volatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae). AB - Serous (granular or venom) glands occur in the skin of almost all species of adult amphibians, and are thought to be the source of a great diversity of chemical compounds. Despite recent advances in their chemistry, odorous volatile substances are compounds that have received less attention, and until now no study has attempted to associate histological data with the presence of these molecules in amphibians, or in any other vertebrate. Given the recent identification of 40 different volatile compounds from the skin secretions of H. pulchellus (a treefrog species that releases a strong odour when handled), we examined the structure, ultrastructure, histochemistry, and distribution of skin glands of this species. Histological analysis from six body regions reveals the presence of two types of glands that differ in their distribution. Mucous glands are homogeneously distributed, whereas serous glands are more numerous in the scapular region. Ultrastructural results indicate that electron-translucent vesicles observed within granules of serous glands are similar to those found in volatile-producing glands from insects and also with lipid vesicles from different organisms. Association among lipids and volatiles is also evidenced from chemical results, which indicate that at least some of the volatile components in H. pulchellus probably originate within the metabolism of fatty acids or the mevalonate pathway. As odorous secretions are often considered to be secreted under stress situations, the release of glandular content was assessed after pharmacological treatments, epinephrine administrated in vivo and on skin explants, and through surface electrical stimulation. Serous glands responded to all treatments, generally through an obvious contraction of myoepithelial cells that surround their secretory portion. No response was observed in mucous glands. Considering these morpho-functional results, along with previous identification of volatiles from H. pulchellus and H. riojanus after electrical stimulation, we suggest that the electron-translucent inclusions found within the granules of serous glands likely are the store sites of volatile compounds and/or their precursors. Histochemical and glandular distribution analyses in five other species of frogs of the hylid tribe Cophomantini, revealed a high lipid content in all the species, whereas a heterogeneous distribution of serous glands is only observed in species of the H. pulchellus group. The distribution pattern of serous glands in members of this species group, and the odorous volatile secretions are probably related to defensive functions. PMID- 26555698 TI - An integrative C. elegans protein-protein interaction network with reliability assessment based on a probabilistic graphical model. AB - In Caenorhabditis elegans, a large number of protein-protein interactions (PPIs) are identified by different experiments. However, a comprehensive weighted PPI network, which is essential for signaling pathway inference, is not yet available in this model organism. Therefore, we firstly construct an integrative PPI network in C. elegans with 12,951 interactions involving 5039 proteins from seven molecular interaction databases. Then, a reliability score based on a probabilistic graphical model (RSPGM) is proposed to assess PPIs. It assumes that the random number of interactions between two proteins comes from the Bernoulli distribution to avoid multi-links. The main parameter of the RSPGM score contains a few latent variables which can be considered as several common properties between two proteins. Validations on high-confidence yeast datasets show that RSPGM provides more accurate evaluation than other approaches, and the PPIs in the reconstructed PPI network have higher biological relevance than that in the original network in terms of gene ontology, gene expression, essentiality and the prediction of known protein complexes. Furthermore, this weighted integrative PPI network in C. elegans is employed on inferring interaction path of the canonical Wnt/beta-catenin pathway as well. Most genes on the inferred interaction path have been validated to be Wnt pathway components. Therefore, RSPGM is essential and effective for evaluating PPIs and inferring interaction path. Finally, the PPI network with RSPGM scores can be queried and visualized on a user interactive website, which is freely available at . PMID- 26555699 TI - The unwelcome trio: HIV plus cutaneous and visceral leishmaniasis. AB - Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of "pathologic alliances," to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established. PMID- 26555697 TI - Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll Like Receptor 4 Dependent. AB - Plasmodium falciparum infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10) in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contributing to vascular dysfunction, blood-brain barrier (BBB) damage and mortality. Endothelial progenitor cells (EPC) are microvascular endothelial cell precursors partly responsible for repair and regeneration of damaged BBB endothelium. Studies have shown that EPC's are depleted in severe malaria patients, but the mechanisms mediating this phenomenon are unknown. Toll-like receptors recognize a wide variety of pathogen-associated molecular patterns generated by pathogens such as bacteria and parasites. We tested the hypothesis that EPC depletion during malaria pathogenesis is a function of heme-induced apoptosis mediated by CXCL10 induction and toll-like receptor (TLR) activation. Heme and CXCL10 concentrations in plasma obtained from malaria patients were elevated compared with non-malaria subjects. EPC numbers were significantly decreased in malaria patients (P < 0.02) and TLR4 expression was significantly elevated in vivo. These findings were confirmed in EPC precursors in vitro; where it was determined that heme-induced apoptosis and CXCL10 expression was TLR4 mediated. We conclude that increased serum heme mediates depletion of EPC during malaria pathogenesis. PMID- 26555700 TI - The Phenomenology and Generation of Positive Mental Imagery in Early Psychosis. AB - BACKGROUND: Theoretical models of depression and bipolar disorder emphasise the importance of positive mental imagery in mood and behaviour. Distressing, intrusive images are common in psychosis; however, little is known about positive imagery experiences or their association with clinical symptoms. The aim of the current study was to examine the phenomenology of positive imagery in early psychosis and the relationship between the characteristics of positive, future oriented imagery and symptom severity. METHOD: Characteristics, thematic content and appraisals of recent self-reported images were examined in 31 people with early psychosis. The vividness and perceived likelihood of deliberately generated, future-oriented images were investigated in relation to clinical symptoms. RESULTS: Eighty-four percent of participants reported experiencing a recent positive image. Themes included the achievement of personal goals, spending enjoyable time with peers and family, loving, intimate relationships and escape from current circumstances. The vividness and perceived likelihood of generated prospective imagery were negatively correlated with levels of depression and social anxiety. CONCLUSIONS: The relationship between emotional problems and the ability to imagine positive, future events may have implications for motivation, mood and goal-directed behaviour in psychosis. Everyday experiences of positive imagery may represent the simulation of future goals, attempts to cope or avoid aversive experiences or idealised fantasy. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: The majority of participants experienced a recent positive image with themes related to goal attainment and social relationships. Depression and social anxiety levels were correlated with the vividness of intentionally generated positive future-oriented images and their perceived likelihood. The assessment of positive imagery in early psychosis appears warranted and may provide insights regarding individual coping strategies, values and goals. PMID- 26555701 TI - A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models. AB - We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a "hidden population". In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdos-Renyi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure. PMID- 26555703 TI - Non-invasive quantification of hepatic steatosis in living, related liver donors using dual-echo Dixon imaging and single-voxel proton spectroscopy. AB - AIM: To evaluate the diagnostic implications of hepatic fat fraction calculated using dual-echo Dixon imaging and (1)H magnetic resonance spectroscopy (MRS) to detect hepatic steatosis in potential liver donors using histopathology as the reference standard. MATERIALS AND METHODS: One hundred and forty-five potential liver donors were included in the study. Magnetic resonance imaging (MRI) was performed using a 1.5 T system using a three-dimensional dual-echo MRI sequence with automated reconstruction of in-phase (IP), out-of-phase (OP), fat-signal only, and water-signal-only images. Hepatic fat fraction was calculated by drawing 15 regions of interest on the IP, OP, fat-only, and water-only images. Single-voxel MRS was performed at echo times (TEs) of 30 ms in the right and left lobes of liver. Liver fat fraction was calculated from water and fat peaks. One hundred and forty-five biopsies were prospectively evaluated for steatosis by a pathologist using traditional determination of the cell-count fraction. MRI and pathology values of steatosis were correlated using Pearson's correlation coefficient. The sensitivity and specificity of each of these methods was calculated using histopathology as the reference standard. Reproducibility was assessed in 40 patients who had repeat scanning within 4-40 days. Measurement error was calculated from the coefficient of variation (CoV) with histopathologically proven <5% fat (n=112). RESULTS: The Bland-Altman limits of agreement with 95% confidence intervals (CI) was -2.9 to 5.3%. The intraclass correlation coefficient (ICC) for interobserver variability and reproducibility was 0.94 (95% CI: 0.91-0.97), 0.92 (95% CI: 0.91-0.97). The CoV was 7.6% (95% CI: 3.4-11.85). The area under the receiver operating characteristic (ROC) curve (AUC) for Dixon imaging 0.89 (95% CI: 0.87-0.91), for MRS 0.88 (95% CI: 0.86 0.90). The sensitivity for detecting <5% fat was 84% and specificity was 90%. CONCLUSION: Combination of dual-echo Dixon imaging and proton MRS is a useful tool for the preoperative diagnosis of hepatic steatosis in potential living liver donors. This can help avoid unnecessary biopsies in these patients. PMID- 26555702 TI - Effects of Etomidate on the Steroidogenesis of Rat Immature Leydig Cells. AB - BACKGROUND: Etomidate is a rapid hypnotic intravenous anesthetic agent. The major side effect of etomidate is the reduced plasma concentration of corticosteroids, leading to the abnormal reaction of adrenals. Cortisol and testosterone biosynthesis has similar biosynthetic pathway, and shares several common steroidogenic enzymes, such as P450 side chain cleavage enzyme (CYP11A1) and 3beta-hydroxysteroid dehydrogenase 1 (HSD3B1). The effect of etomidate on Leydig cell steroidogenesis during the cell maturation process is not well established. METHODOLOGY: Immature Leydig cells isolated from 35 day-old rats were cultured with 30 MUM etomidate for 3 hours in combination with LH, 8Br-cAMP, 25R-OH cholesterol, pregnenolone, progesterone, androstenedione, testosterone and dihydrotestosterone, respectively. The concentrations of 5alpha-androstanediol and testosterone in the media were measured by radioimmunoassay. Leydig cells were cultured with various concentrations of etomidate (0.3-30 MUM) for 3 hours, and total RNAs were extracted. Q-PCR was used to measure the mRNA levels of following genes: Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14. The testis mitochondria and microsomes from 35-day-old rat testes were prepared and used to detect the direct action of etomidate on CYP11A1 and HSD3B1 activity. RESULTS AND CONCLUSIONS: In intact Leydig cells, 30 MUM etomidate significantly inhibited androgen synthesis. Further studies showed that etomidate also inhibited the LH- stimulated androgen production. On purified testicular mitochondria and ER fractions, etomidate competitively inhibited both CYP11A1 and HSD3B1 activities, with the half maximal inhibitory concentration (IC50) values of 12.62 and 2.75 MUM, respectively. In addition, etomidate inhibited steroidogenesis-related gene expression. At about 0.3 MUM, etomidate significantly inhibited the expression of Akr1C14. At the higher concentration (30 MUM), it also reduced the expression levels of Cyp11a1, Hsd17b3 and Srd5a1. In conclusion, etomidate directly inhibits the activities of CYP11A1 and HSD3B1, and the expression levels of Cyp11a1 and Hsd17b3, leading to the lower production of androgen by Leydig cells. PMID- 26555704 TI - MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function. AB - Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp 19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis. PMID- 26555705 TI - The IL-33 receptor (ST2) regulates early IL-13 production in fungus-induced allergic airway inflammation. AB - Allergic airway inflammation (AAI) in response to environmental antigens is an increasing medical problem, especially in the Western world. Type 2 interleukins (IL) are central in the pathological response but their importance and cellular source(s) often rely on the particular allergen. Here, we highlight the cellular sources and regulation of the prototypic type 2 cytokine, IL-13, during the establishment of AAI in a fungal infection model using Cryptococcus neoformans. IL-13 reporter mice revealed a rapid onset of IL-13 competence within innate lymphoid cells type 2 (ILC2) and IL-33R(+) T helper (Th) cells. ILC2 showed IL-33 dependent proliferation upon infection and significant IL-13 production. Th cells essentially required IL-33 to become either GATA3(+) or GATA3(+)/Foxp3(+) hybrids. GATA3(+) Th cells almost exclusively contributed to IL-13 production but hybrid GATA3(+)/Foxp3(+) Th cells did not. In addition, alveolar macrophages upregulated the IL-33R and subsequently acquired a phenotype of alternative activation (Ym1(+), FIZZ1(+), and arginase-1(+)) linked to type 2 immunity. Absence of adaptive immunity in rag2(-/-) mice resulted in attenuated AAI, revealing the need for Th2 cells for full AAI development. Taken together, in pulmonary cryptococcosis ILC2 and GATA3(+) Th2 cells produce early IL-13 largely IL-33R-dependent, thereby promoting goblet cell metaplasia, pulmonary eosinophilia, and alternative activation of alveolar macrophages. PMID- 26555706 TI - A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy. PMID- 26555707 TI - Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl Lewis(x) to increase binding to airway epithelial cells. AB - Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non CF individuals, mucus of CF airways is enriched in sialyl-Lewis(x), a preferred binding receptor for PA. Notably, the levels of sialyl-Lewis(x) directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewis(x) modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewis(x) in both mouse airways and in primary and immortalized CF and non CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewis(x), through a tumor necrosis factor (TNF)-alpha mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl Lewis(x) and anti-TNF-alpha attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewis(x). PMID- 26555710 TI - Heterogeneous chemistry and reaction dynamics of the atmospheric oxidants, O3, NO3, and OH, on organic surfaces. AB - Heterogeneous chemistry of the most important atmospheric oxidants, O3, NO3, and OH, plays a central role in regulating atmospheric gas concentrations, processing aerosols, and aging materials. Recent experimental and computational studies have begun to reveal the detailed reaction mechanisms and kinetics for gas-phase O3, NO3, and OH when they impinge on organic surfaces. Through new research approaches that merge the fields of traditional surface science with atmospheric chemistry, researchers are developing an understanding for how surface structure and functionality affect interfacial chemistry with this class of highly oxidizing pollutants. Together with future research initiatives, these studies will provide a more complete description of atmospheric chemistry and help others more accurately predict the properties of aerosols, the environmental impact of interfacial oxidation, and the concentrations of tropospheric gases. PMID- 26555708 TI - HIV-1-negative female sex workers sustain high cervical IFNE, low immune activation, and low expression of HIV-1-required host genes. AB - Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: P<0.001) together with lower cervical gene expression of genes associated with leukocyte homing and chemotaxis. FSWs also had increased levels of interferon-E (IFNE) gene and protein expression in the cervical epithelium together with reduced expression of genes associated with HIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses. PMID- 26555711 TI - The Moreau Strain of Bacillus Calmette-Guerin (BCG) for High-Risk Non-Muscle Invasive Bladder Cancer: An Alternative during Worldwide BCG Shortage? AB - BACKGROUND: Bacillus Calmette-Guerin (BCG) is the standard of care for adjuvant intravesical instillation therapy for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection. Increasing evidence suggests that there are marked differences in outcomes according to BCG substrains. BCG-Moreau was recently introduced to the European market to cover the issue of BCG shortage, but there are little data regarding the oncologic efficacy. METHODS: We retrospectively analyzed 295 consecutive patients, who received adjuvant intravesical instillation therapy with BCG-Moreau for intermediate- and high-risk NMIBC between October 2007 and April 2013 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. RESULTS: Median age was 66 years (interquartile range 59-74, mean 65.9 years). According to the EAU risk group, 76 patients presented with intermediate-risk and 219 patients with high-risk NMIBC. The 5-year recurrence-free survival and progression-free survival rate was 64.8% (95% CI 52.8-74.4) and 81.4% (95% CI 65.2-90.2), respectively. CONCLUSIONS: BCG Moreau is an effective substrain for adjuvant instillation therapies of NMIBC, and outcomes appear to be comparable to series using other substrains. During worldwide shortage of BCG-TICE, Connaught and RIVM, BCG-Moreau may serve as an equally effective alternative. PMID- 26555712 TI - Gut microbiota and diet in patients with different glucose tolerance. AB - Type 2 diabetes (T2D) is a serious disease. The gut microbiota (GM) has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. To investigate the GM composition in association with the dietary patterns in patients with different glucose tolerance, we analyzed 92 patients: with normal glucose tolerance (n=48), prediabetes (preD, n=24), and T2D (n=20). Metagenomic analysis was performed using 16S rRNA sequencing. The diet has been studied by a frequency method with a quantitative evaluation of food intake using a computer program. Microbiota in the samples was predominantly represented by Firmicutes, in a less degree by Bacteroidetes. Blautia was a dominant genus in all samples. The representation of Blautia, Serratia was lower in preD than in T2D patients, and even lower in those with normal glucose tolerance. After the clustering of the samples into groups according to the percentage of protein, fat, carbohydrates in the diet, the representation of the Bacteroides turned to be lower and Prevotella abundance turned to be higher in carbohydrate cluster. There were more patients with insulin resistance, T2D in the fat-protein cluster. Using the Calinski-Harabasz index identified the samples with more similar diets. It was discovered that half of the patients with a high-fat diet had normal tolerance, the others had T2D. The regression analysis showed that these T2D patients also had a higher representation of Blautia. Our study provides the further evidence concerning the structural modulation of the GM in the T2DM pathogenesis depending on the dietary patterns. PMID- 26555713 TI - Molecular interaction investigation between three CdTe:Zn(2+) quantum dots and human serum albumin: A comparative study. AB - Water-soluble Zn-doped CdTe quantum dots (CdTe:Zn(2+) QDs) have attracted great attention in biological and biomedical applications. In particular, for any potential in vivo application, the interaction of CdTe:Zn(2+) QDs with human serum albumin (HSA) is of greatest importance. As a step toward the elucidation of the fate of CdTe:Zn(2+) QDs introduced to organism, the molecular interactions between CdTe:Zn(2+) QDs with three different sizes and HSA were systematically investigated by spectroscopic techniques. Three CdTe:Zn(2+) QDs with maximum emission of 514 nm (green QDs, GQDs), 578 nm (yellow QDs, YQDs), and 640 nm (red QDs, RQDs) were tested. The binding of CdTe:Zn(2+) QDs with HSA was a result of the formation of HSA-QDs complex and electrostatic interactions played major roles in stabilizing the complex. The Stern-Volmer quenching constant, associative binding constant, and corresponding thermodynamic parameters were calculated. The site-specific probe competitive experiments revealed that the binding location of CdTe:Zn(2+) QDs with HSA was around site I. The microenvironmental and conformational changes of HSA induced by CdTe:Zn(2+) QDs were analyzed. These results suggested that the conformational change of HSA was dramatically at secondary structure level and the biological activity of HSA was weakened in the present of CdTe:Zn(2+) QDs with bigger size. PMID- 26555714 TI - Muscle contributions to centre of mass acceleration during turning gait in typically developing children: A simulation study. AB - Turning while walking requires substantial joint kinematic and kinetic adaptations compared to straight walking in order to redirect the body centre of mass (COM) towards the new walking direction. The role of muscles and external forces in controlling and redirecting the COM during turning remains unclear. The aim of this study was to compare the contributors to COM medio-lateral acceleration during 90 degrees pre-planned turns about the inside limb (spin) and straight walking in typically developing children. Simulations of straight walking and turning gait based on experimental motion data were implemented in OpenSim. The contributors to COM global medio-lateral acceleration during the approach (outside limb) and turn (inside limb) stance phase were quantified via an induced acceleration analysis. Changes in medio-lateral COM acceleration occurred during both turning phases, compared to straight walking (p<0.001). During the approach, outside limb plantarflexors (soleus and medial gastrocnemius) contribution to lateral (away from the turn side) COM acceleration was reduced (p<0.001), whereas during the turn, inside limb plantarflexors (soleus and gastrocnemii) contribution to lateral acceleration (towards the turn side) increased (p<=0.013) and abductor (gluteus medius and minimus) contribution medially decreased (p<0.001), compared to straight walking, together helping accelerate the COM towards the new walking direction. Knowledge of the changes in muscle contributions required to modulate the COM position during turning improves our understanding of the control mechanisms of gait and may be used clinically to guide the management of gait disorders in populations with restricted gait ability. PMID- 26555715 TI - Ultrastructural alterations of osteocyte morphology via loaded implants in rabbit tibiae. AB - Osteocytes are crucial cells that control bone responses to mechanical loading. However, the effects of mechanical loading on osteocytes around dental implants are unclear. The aim of this study was to investigate whether mechanical loading via bone-integrated implants influences osteocyte number and morphology in the surrounding bone. Fourteen anodized Ti-6Al-4V alloy dental implants were placed in seven Japanese white rabbits, and implants in each rabbit were subjected to mechanical loading (50N, 3Hz for 1800 cycles, 2 days/week) along the implant long axis. Eight weeks after the initiation of loading, histomorphometric analysis and microcomputed tomography were performed. Scanning electron microscopy (SEM) was also performed with an acid etching technique using longitudinal and cross sectional specimens. More bone formation around loaded implants was noted. In the implant neck, osteocytes tended to be more spherical with increased dendrite processes around loaded implants, while spindle-shaped osteocytes without increased dendrite processes were observed around unloaded implants in both longitudinal and cross-sectional images. In the bottom area, morphological changes in osteocytes were observed around loaded implants; however, dendrite processes did not differ in longitudinal or cross-sectional images, regardless of mechanical loading. These findings indicate that increased osteocyte numbers and developed dendrite processes are associated with anabolic bone responses to mechanical loading. The combination of acid etching and SEM imaging is a useful technique to assess ultrastructural osteocyte morphology around dental implants. PMID- 26555716 TI - Rigid and non-rigid geometrical transformations of a marker-cluster and their impact on bone-pose estimation. AB - When stereophotogrammetry and skin-markers are used, bone-pose estimation is jeopardised by the soft tissue artefact (STA). At marker-cluster level, this can be represented using a modal series of rigid (RT; translation and rotation) and non-rigid (NRT; homothety and scaling) geometrical transformations. The NRT has been found to be smaller than the RT and claimed to have a limited impact on bone pose estimation. This study aims to investigate this matter and comparatively assessing the propagation of both STA components to bone-pose estimate, using different numbers of markers. Twelve skin-markers distributed over the anterior aspect of a thigh were considered and STA time functions were generated for each of them, as plausibly occurs during walking, using an ad hoc model and represented through the geometrical transformations. Using marker-clusters made of four to 12 markers affected by these STAs, and a Procrustes superimposition approach, bone-pose and the relevant accuracy were estimated. This was done also for a selected four marker-cluster affected by STAs randomly simulated by modifying the original STA NRT component, so that its energy fell in the range 30 90% of total STA energy. The pose error, which slightly decreased while increasing the number of markers in the marker-cluster, was independent from the NRT amplitude, and was always null when the RT component was removed. It was thus demonstrated that only the RT component impacts pose estimation accuracy and should thus be accounted for when designing algorithms aimed at compensating for STA. PMID- 26555717 TI - Someone's lurking in the dark: The role of state anxiety on attention deployment to threat-related stimuli. AB - Anxious states can alter attention, impairing goal-directed processing in favor of bottom-up capture. However, it is still unclear whether anxiety-related biases already influence the earliest stage of information processing, especially for unattended threat-related stimuli. Here we tested, using EEG, if the amplitude of the first component of the Visual Evoked Potentials (C1) to simple visual stimuli (either neutral or threat-related) varied depending on anxiety level and task demands. Results showed that anxiety altered goal-directed processing, reducing P300 amplitude to target stimuli, while it increased the C1 to irrelevant stimuli, regardless of their emotional content. Moreover, enhanced load at fixation reduced the amplitude of this component to neutral stimuli, but this early filtering effect was abolished by state anxiety. These results shed light on the time-course of attentional biases in anxiety, confirming that this transient state can enhance bottom-up capture as early as in V1, at the expense of goal-directed processing. PMID- 26555720 TI - Extraction and Identification of the Pigment in the Adductor Muscle Scar of Pacific Oyster Crassostrea gigas. AB - In this study, UV (ultraviolet) and IR (infrared radiation) spectral analysis were integrated to identify the pigment in the adductor muscle scar of the Pacific oyster Crassostrea gigas. The pigment was extracted from the adductor muscle scars of cleaned oyster shells that were pulverized, hydrolyzed in hot hydrochloric acid, purified with diethyl ether, and dissolved in 0.01 mL/L NaOH. The maximum absorption of the pigment in the UV absorption spectrum within the range of 190-500 nm was observed between 210-220 nm. The UV absorbance decreased with increasing wavelength which was consistent with the UV spectral absorption characteristics of melanin. In addition, Fourier transform infrared spectroscopy scanning revealed characteristic absorption peaks that emerged near 3440 cm-1 and 1630 cm-1, which was consistent with infrared scanning features of eumelanin (a type of melanin). This study has demonstrated for the first time that the pigment in the adductor muscle scar of the Pacific oyster is melanin, hinting that the adductor muscle could be another organ pigmenting the mollusc shell with melanin other than mantle. PMID- 26555718 TI - Synaptic interactions and inhibitory regulation in auditory cortex. AB - This Special Issue focuses on the auditory-evoked mismatch negativity (MMN), an electrophysiological index of change, and its reduction in schizophrenia. The following brief review is an attempt to complement the behavioral and clinical contributions to the Special Issue by providing basic information on synaptic interactions and processing in auditory cortex. A key observation in previous studies is that the MMN involves activation of cortical N-methyl-D-aspartate (NMDA) receptors. Yet, NMDA receptor activation is regulated by a number of synaptic events, which also may contribute to the MMN reduction in schizophrenia. Accordingly, this review will focus on synaptic interactions, notably inhibitory regulation of NMDA receptor-mediated activity, in auditory cortex. PMID- 26555721 TI - Visualization of Chondrocyte Intercalation and Directional Proliferation via Zebrabow Clonal Cell Analysis in the Embryonic Meckel's Cartilage. AB - Development of the vertebrate craniofacial structures requires precise coordination of cell migration, proliferation, adhesion and differentiation. Patterning of the Meckel's cartilage, a first pharyngeal arch derivative, involves the migration of cranial neural crest (CNC) cells and the progressive partitioning, proliferation and organization of differentiated chondrocytes. Several studies have described CNC migration during lower jaw morphogenesis, but the details of how the chondrocytes achieve organization in the growth and extension of Meckel's cartilage remains unclear. The sox10 restricted and chemically induced Cre recombinase-mediated recombination generates permutations of distinct fluorescent proteins (RFP, YFP and CFP), thereby creating a multi spectral labeling of progenitor cells and their progeny, reflecting distinct clonal populations. Using confocal time-lapse photography, it is possible to observe the chondrocytes behavior during the development of the zebrafish Meckel's cartilage. Multispectral cell labeling enables scientists to demonstrate extension of the Meckel's chondrocytes. During extension phase of the Meckel's cartilage, which prefigures the mandible, chondrocytes intercalate to effect extension as they stack in an organized single-cell layered row. Failure of this organized intercalating process to mediate cell extension provides the cellular mechanistic explanation for hypoplastic mandible that we observe in mandibular malformations. PMID- 26555722 TI - A Case Study of Petroleum Degradation in Different Soil Textural Classes. AB - BACKGROUND: Patents have been granted for a number of techniques for petroleum biodegradation including use of micro-organisms for degradation of hydrocarbon based substances and for hydrocarbon degradation in oil reservoirs, but there is a dearth of information on hydrocarbon degradation in different soil textures. OBJECTIVE: Hence, this work investigated the effects of different soil textures on degradation of petroleum hydrocarbons during a six-week period. METHODS: Five soil textural classes commonly found in Port Harcourt metropolis, Nigeria, namely sand, loamy sand, sandy loam, silty clay and clay, were employed. The soils were contaminated with the same amount of crude oil and then remediated by biostimulation. Selected soil properties were monitored over time. RESULTS: Bacterial numbers declined significantly in the fine soil textures after petroleum contamination, but were either unaffected or increased significantly in the coarser soil textures. Hydrocarbon losses ranged from 42% - 99%; the sandy loam had the highest, while the clay soil had the least total hydrocarbon content (THC) reduction. The total heterotrophic bacterial (THB) counts generally corroborated the THC results. Fold increase in bacterial numbers due to remediation treatment decreased with increasing clay content. CONCLUSION: The results suggest that higher sand than clay content of soil favours faster hydrocarbon degradation. Hydrocarbon degradation efficiency increased with silt content among soil groupings such as fine and coarse soils but not necessarily with increasing silt content of soil. Thus, there seems to be cut-off sand and clay contents in soil at which the effect of the silt content becomes significant. PMID- 26555723 TI - Human CD180 Transmits Signals via the PIM-1L Kinase. AB - Toll-like receptors (TLRs) are important sensors of the innate immune system that recognize conserved structural motifs and activate cells via a downstream signaling cascade. The CD180/MD1 molecular complex is an unusual member of the TLR family, since it lacks the components that are normally required for signal transduction by other TLRs. Therefore the CD180/MD 1 complex has been considered of being incapable of independently initiating cellular signals. Using chemogenetic approaches we identified specifically the membrane bound long form of PIM-1 kinase, PIM-1L as the mediator of CD180-dependent signaling. A dominant negative isoform of PIM-1L, but not of other PIM kinases, inhibited signaling elicited by cross-linking of CD180, and this effect was phenocopied by PIM inhibitors. PIM-1L was directed to the cell membrane by its N-terminal extension, where it colocalized and physically associated with CD180. Triggering CD180 also induced increased phosphorylation of the anti-apoptotic protein BAD in a PIM kinase-dependent fashion. Also in primary human B cells, which are the main cells expressing CD180 in man, cross-linking of CD180 by monoclonal antibodies stimulated cell survival and proliferation that was abrogated by specific inhibitors. By associating with PIM-1L, CD180 can thus obtain autonomous signaling capabilities, and this complex is then channeling inflammatory signals into B cell survival programs. Pharmacological inhibition of PIM-1 should therefore provide novel therapeutic options in diseases that respond to innate immune stimulation with subsequently increased B cell activity, such as lupus erythematosus or myasthenia gravis. PMID- 26555724 TI - Safety and Outcome of Pharmacy-Led Vancomycin Dosing and Monitoring. AB - BACKGROUND: Therapeutic vancomycin trough levels correlate with therapeutic success and the development of renal failure. In this study, we aimed to describe the safety and outcome of pharmacy-led vancomycin dosing and monitoring. METHODS: We included adults requiring vancomycin for >48 h and who had a vancomycin trough level drawn near steady state. The primary outcome of the comparison was the achievement of therapeutic trough levels, defined as 10-20 ug/ml. Secondary outcome included acute renal failure. We compared these outcomes before and after the implementation of pharmacy-led vancomycin dosing and monitoring. RESULT: During the study period, a total of 278 patients were in the preimplementation phase and 286 were in the postintervention phase. There was a clear increase in the percentage of patients achieving the therapeutic range (50.5 vs. 79.7%, p = 0.0001) and an increase in the percentage of levels within the therapeutic range (31.6 vs. 59.1%; p = 0.0001). The number of cases receiving vancomycin increased by 5% and the duration of therapy decreased by 19.5%. More patients attained a therapeutic range of 10-20 ug/ml (i.e. the level was 31.6% in the preintervention and 59.1% in the postintervention phase). CONCLUSIONS: A higher percentage of patients achieved a therapeutic range and less nephrotoxicity when using a pharmacy-led protocol for vancomycin dosing. PMID- 26555725 TI - Journal Impact Factor Shapes Scientists' Reward Signal in the Prospect of Publication. AB - The incentive structure of a scientist's life is increasingly mimicking economic principles. While intensely criticized, the journal impact factor (JIF) has taken a role as the new currency for scientists. Successful goal-directed behavior in academia thus requires knowledge about the JIF. Using functional neuroimaging we examined how the JIF, as a powerful incentive in academia, has shaped the behavior of scientists and the reward signal in the striatum. We demonstrate that the reward signal in the nucleus accumbens increases with higher JIF during the anticipation of a publication and found a positive correlation with the personal publication record (pJIF) supporting the notion that scientists have incorporated the predominant reward principle of the scientific community in their reward system. The implications of this behavioral adaptation within the ecological niche of the scientist's habitat remain unknown, but may also have effects which were not intended by the community. PMID- 26555726 TI - Validation of a base deficit-based trauma prediction model and comparison with TRISS and ASCOT. AB - BACKGROUND: Base deficit provides a more objective indicator of physiological stress following injury as compared with vital signs constituting the revised trauma score (RTS). We have previously developed a base deficit-based trauma survival prediction model [base deficit and injury severity score model (BISS)], in which RTS was replaced by base deficit as a measurement of physiological imbalance. PURPOSE: To externally validate BISS in a large cohort of trauma patients and to compare its performance with established trauma survival prediction models including trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT). Moreover, we examined whether the predictive accuracy of BISS model could be improved by replacement of injury severity score (ISS) by new injury severity score (NISS) in the BISS model (BNISS). METHODS: In this retrospective, observational study, clinical data of 3737 trauma patients (age >=15 years) admitted consecutively from 2003 to 2007 were obtained from a prospective trauma registry to calculate BISS, TRISS, and ASCOT models. The models were evaluated in terms of discrimination [area under curve (AUC)] and calibration. RESULTS: The in-hospital mortality rate was 8.1 %. The discriminative performance of BISS to predict survival was similar to that of TRISS and ASCOT [AUCs of 0.883, 95 % confidence interval (CI) 0.865-0.901 for BISS, 0.902, 95 % CI 0.858-0.946 for TRISS and 0.864, 95 % CI 0.816-0.913 for ASCOT]. Calibration tended to be optimistic in all three models. The updated BNISS had an AUC of 0.918 indicating that substitution of ISS with NISS improved model performance. CONCLUSIONS: The BISS model, a base deficit-based trauma model for survival prediction, showed equivalent performance as compared with that of TRISS and ASCOT and may offer a more simplified calculation method and a more objective assessment. Calibration of BISS model was, however, less good than that of other models. Replacing ISS by NISS can considerably improve model accuracy, but further confirmation is needed. PMID- 26555727 TI - Major trauma in winter sports: an international trauma database analysis. AB - PURPOSE: The aim of this study was to compare the demographics, injury patterns, and outcomes following major trauma between Alpine skiing, snowboarding, and sledding winter sports. METHODS: An international population-based prospective trauma database (TraumaRegister DGU(r)) was analyzed for demographic data, types and severity of injuries [body regions, Injury Severity Score (ISS)], early physiology [Glasgow Coma Scale (GCS), blood pressure, body temperature], rescue modality, surgical care, length of stay, and major complications (shock, multiple organ failure mortality). Participating countries included Germany, Austria, Switzerland, Finland, Slovenia, Belgium, Luxembourg, and The Netherlands. RESULTS: A total of 243 winter sport athletes with major trauma were identified (1993-2012), and subjects were divided into Alpine skiers (n = 174), snowboarders (n = 29), and sledders (n = 40). Athletes were predominantly male and presented hypothermic at emergency room arrival, despite a large proportion of air rescue (77 %). Alpine skiing was associated with higher injury severity (ISS 20.8 +/- 14.0, p = 0.010) when compared with snowboarding (ISS 18.7 +/- 14.0) and sledding (ISS 13.8 +/- 9.5). Snowboarding was associated with the highest pre-hospital intubation rate (40.9 %, p = 0.007), despite comparable GCS values and prevalence of loss of consciousness at scene. The injury patterns were different between the three groups. Skiing was associated with head (47.1 %), chest (40.2 %, p = 0.047), and spinal injuries (40.9 %, p = 0.022). Snowboarding was associated with the highest percentage of upper extremity trauma. Sledders had the highest prevalence of facial and lower extremity trauma. CONCLUSIONS: Alpine skiing, snowboarding, and sledding result in different injury patterns and affect various age groups. Our data suggest an increased risk for chest and spinal injuries in Alpine skiers. Due to high-energy injury mechanisms, all three winter sports involve a risk of severe multiple trauma. While all athlete groups required a high rate of emergency surgery procedures, the observed in-hospital mortality from winter sports remains low. PMID- 26555728 TI - Does MIPO of fractures of the distal femur result in more rotational malalignment than ORIF? A retrospective study. AB - PURPOSE: Intraoperative control of rotational malalignment poses a big challenge for surgeons when using modern MIPO (minimally invasive plate osteosynthesis) techniques. We hypothesized that distal femoral fractures treated with MIPO technique are more often fixed in malrotation than those treated with open reduction internal fixation (ORIF). METHODS: In this retrospective study, we identified 20 patients who met the inclusion criteria and agreed to take part in the study. In ten patients MIPO was applied, in the other ten ORIF was used. Mean age was 44.8 (19-71 years). Functional status was assessed using clinical scores (Harris Hip Score, WOMAC Hip, KS Score, WOMAC Knee, Kujala Score). Rotational alignment was assessed with magnetic resonance imaging and compared to the opposite leg. RESULTS: We discovered a significant difference in the mean rotational difference between the MIPO group (14.3 degrees ) and the ORIF group (5.2 degrees ). Functionally, patients in the ORIF group outperformed patients in the MIPO group in all clinical scoring systems although no one proved to be statistically significant. MIPO technique was associated with significantly more rotational malalignment compared to ORIF in distal femur fracture fixation. However, implant failure and nonunion was more common in the ORIF group, with a revision rate of 3 versus 1 in the ORIF group. Clinical scoring did not significantly different between both groups. CONCLUSION: Taking into account the undisputable advantages of minimally invasive surgery, improved teaching of methods to avoid malrotation as well as regular postoperative investigations to detect any malrotation should be advocated. PMID- 26555729 TI - Comparison of MRI, CT and bone scintigraphy for suspected scaphoid fractures. AB - PURPOSE: The best diagnostic modality for confirmation of the diagnosis of a scaphoid fracture that is not visible on the initial radiograph (occult scaphoid fracture) is still subject of debate. The aim of this study was to compare the accuracy of magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy (BS) for the diagnosis of these occult scaphoid fractures. PATIENTS AND METHODS: In a study period of 12 months, 33 consecutive patients with a clinically suspected scaphoid fracture without a fracture on the scaphoid radiographs were evaluated with MRI, CT and BS. In case of a discrepancy between the diagnostic modalities, the final diagnosis was based on standardised follow up with clinical examination and a repeated radiograph. RESULTS: Three of the 33 patients had a scaphoid fracture. MRI missed one scaphoid fracture and did not over-diagnose. CT missed two scaphoid fractures and did not over-diagnose. BS missed no scaphoid fractures and over-diagnosed one scaphoid fracture in a patient with a fracture of the trapezium. CONCLUSION: This study shows that neither MRI, nor CT and BS are 100 % accurate in diagnosing occult scaphoid fractures. MRI and CT miss fractures, and BS tends to over-diagnose. The specific advantages and limitations of each diagnostic modality should be familiar to the treating physicians and taken into consideration during the diagnostic process. PMID- 26555730 TI - Performance Evaluation of Resource Management in Cloud Computing Environments. AB - Cloud computing is a computational model in which resource providers can offer on demand services to clients in a transparent way. However, to be able to guarantee quality of service without limiting the number of accepted requests, providers must be able to dynamically manage the available resources so that they can be optimized. This dynamic resource management is not a trivial task, since it involves meeting several challenges related to workload modeling, virtualization, performance modeling, deployment and monitoring of applications on virtualized resources. This paper carries out a performance evaluation of a module for resource management in a cloud environment that includes handling available resources during execution time and ensuring the quality of service defined in the service level agreement. An analysis was conducted of different resource configurations to define which dimension of resource scaling has a real influence on client requests. The results were used to model and implement a simulated cloud system, in which the allocated resource can be changed on-the-fly, with a corresponding change in price. In this way, the proposed module seeks to satisfy both the client by ensuring quality of service, and the provider by ensuring the best use of resources at a fair price. PMID- 26555731 TI - Combining powers of linkage and association mapping for precise dissection of QTL controlling resistance to gray leaf spot disease in maize (Zea mays L.). AB - BACKGROUND: Gray Leaf Spot (GLS causal agents Cercospora zeae-maydis and Cercospora zeina) is one of the most important foliar diseases of maize in all areas where the crop is being cultivated. Although in the USA the situation with GLS severity is not as critical as in sub-Saharan Africa or Brazil, the evidence of climate change, increasing corn monoculture as well as the narrow genetic base of North American resistant germplasm can turn the disease into a serious threat to US corn production. The development of GLS resistant cultivars is one way to control the disease. In this study we combined the high QTL detection power of genetic linkage mapping with the high resolution power of genome-wide association study (GWAS) to precisely dissect QTL controlling GLS resistance and identify closely linked molecular markers for robust marker-assisted selection and trait introgression. RESULTS: Using genetic linkage analysis with a small bi-parental mapping population, we identified four GLS resistance QTL on chromosomes 1, 6, 7, and 8, which were validated by GWAS. GWAS enabled us to dramatically increase the resolution within the confidence intervals of the above-mentioned QTL. Particularly, GWAS revealed that QTLGLSchr8, detected by genetic linkage mapping as a locus with major effect, was likely represented by two QTL with smaller effects. Conducted in parallel, GWAS of days-to-silking demonstrated the co localization of flowering time QTL with GLS resistance QTL on chromosome 7 indicating that either QTLGLSchr7 is a flowering time QTL or it is a GLS resistance QTL that co-segregates with the latter. As a result, this genetic linkage - GWAS hybrid mapping system enabled us to identify one novel GLS resistance QTL (QTLGLSchr8a) and confirm with more refined positions four more previously mapped QTL (QTLGLSchr1, QTLGLSchr6, QTLGLSchr7, and QTLGLSchr8b). Through the novel Single Donor vs. Elite Panel method we were able to identify within QTL confidence intervals SNP markers that would be suitable for marker assisted selection of gray leaf spot resistant genotypes containing the above mentioned GLS resistance QTL. CONCLUSION: The application of a genetic linkage - GWAS hybrid mapping system enabled us to dramatically increase the resolution within the confidence interval of GLS resistance QTL by-passing labor- and time intensive fine mapping. This method appears to have a great potential to accelerate the pace of QTL mapping projects. It is universal and can be used in the QTL mapping projects in any crops. PMID- 26555733 TI - Back to monoxeny: Phytomonas nordicus descended from dixenous plant parasites. AB - The trypanosomatid Phytomonas nordicus parasitizing the predatory bug Troilus luridus was described at the twilight of the morphotype-based systematics. Despite its monoxenous life cycle, this species was attributed to the dixenous genus Phytomonas due to the presence of long twisted promastigotes and development of flagellates in salivary glands. However, these characteristics were considered insufficient for proving the phytomonad nature of the species and therefore its description remained virtually unnoticed. Here, we performed molecular phylogenetic analyses using 18S ribosomal RNA (rRNA) gene and region containing internal trascribed spacers (ITS) 1 and 2 and convincingly demonstrated the affinity of P. nordicus to the genus Phytomonas. In addition, we investigated its development in the salivary glands. We argue that in many aspects the life cycle of monoxenous P. nordicus resembles that of its dixenous relatives represented by tomato-parasitizing Phytomonas serpens. PMID- 26555732 TI - An outbreak of acute delirium from exposure to the synthetic cannabinoid AB CHMINACA. AB - BACKGROUND: Synthetic cannabinoid containing products are a public health threat as reflected by a number of outbreaks of serious adverse health effects over the past 4 years. The designer drug epidemic is characterized by the rapid turnover of synthetic cannabinoid compounds on the market which creates a challenge in identifying the particular etiology of an outbreak, confirming exposure in cases, and providing current information to law enforcement. RESULTS: Between 28 May 2014 and 8 June 2014, 35 patients were evaluated and treated at the University of Florida Health Medical Center in Gainesville following reported exposure to a synthetic cannabinoid containing product obtained from a common source. Patients demonstrated acute delirium (24) and seizures (14), and five required ventilator support and ICU-level care; none died. The presence of N-[(1S)-1-(aminocarbonyl) 2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA), or one of its predicted metabolites was confirmed in 15 of 21 cases. A rapid public health response and aggressive public messaging prevented further morbidity, identified the source, and led to law enforcement seizure of the implicated product. DISCUSSION: The significance of this outbreak lies as much in the rapid occurrence of unpredictable, life-threatening adverse health effects from a newly identified synthetic cannabinoid compound as it does in the multidisciplinary investigation and novel partnership between local public health, the laboratory, and the chemical industry, resulting in termination of the outbreak. CONCLUSION: A coordinated response and collaboration between law enforcement, the local public health, emergency medical services and Health Center staff, were all key interventions in preventing a more substantial public health outbreak resulting from use of a novel synthetic cannabinoid compound. Real time collaborations between toxicology laboratories, suppliers of analytical standards and the public health system may be useful in the face of future novel chemical exposures. PMID- 26555734 TI - Ultrastructure and phylogeny of Glugea arabica n. sp. (Microsporidia), infecting the marine fish Epinephelus polyphekadion from the Red Sea. AB - A new microsporidian species, Glugea arabica n. sp., is reported infecting the intestinal wall of the marine teleost Epinephelus polyphekadion (=microdon) collected from the Red Sea coast off Saudi Arabia, and described on the basis of microscopic and molecular procedures. Spherical blackish xenomas formed parasitophorous vacuoles completely packed with several parasitic developmental stages, including spores. The nuclei were monokaryotic in all developmental stages. Spores were ellipsoidal to pyriform and measured 6.3 +/- 0.3 (5.9-6.6) MUm in length and 3.3 +/- 0.4 (2.9-3.7) MUm in width. A lamellar polaroplast surrounded the uncoiled portion of the polar filament, which extended into the spore's posterior pole and formed 27-29 coils organized in three or four rows. The posterior vacuole, located at the spore's posterior pole, appeared surrounded by the polar filament coils and displayed an irregular matrix composed of light material, in which was located the posterosome. Molecular analysis of the rRNA genes, including the ITS region, was performed using maximum parsimony, neighbor joining and maximum likelihood methodologies. The ultrastructural features observed, in combination with the molecular data analysed, suggests the parasite to be a new species of the genus Glugea. PMID- 26555735 TI - The influence of zooplankton enrichment on the microbial loop in a shallow, eutrophic lake. AB - With increasing primary productivity, ciliates may become the most important members of the microbial loop and form a central linkage in the transformation of microbial production to upper trophic levels. How metazooplankters, especially copepods, regulate ciliate community structure in shallow eutrophic waters is not completely clear. We carried out mesocosm experiments with different cyclopoid copepod enrichments in a shallow eutrophic lake to examine the responses of ciliate community structure and abundance to changes in cyclopoid copepod biomass and to detect any cascading effects on bacterioplankton and edible phytoplankton. Our results indicate that an increase in copepod zooplankton biomass favours the development of small-sized bacterivorous ciliates. This effect is unleashed by the decline of predaceous ciliate abundance, which would otherwise graze effectively on the small-sized ciliates. The inverse relationship between crustacean zooplankton and large predaceous ciliates is an important feature adjusting not only the structure of the ciliate community but also the energy transfer between meta- and protozooplankton. Still we could not detect any cascading effects on bacterio- or phytoplankton that would be caused by the structural changes in the ciliate community. PMID- 26555736 TI - Conserved histidine residues at the ferroxidase centre of the Campylobacter jejuni Dps protein are not strictly required for metal binding and oxidation. AB - Iron is an essential micronutrient for living organisms as it is involved in a broad variety of important biological processes. However, free iron inside the cell could be potentially toxic, generating hydroxyl radicals through the Fenton reaction. Dps (DNA-binding protein from starved cells) belongs to a subfamily of ferritins and can store iron atoms inside the dodecamer. The presence of a ferroxidase centre, composed of highly conserved residues, is a signature of this protein family. In this study, we analysed the role of two conserved histidine residues (H25 and H37) located at the ferroxidase centre of the Campylobacter jejuni Dps protein by replacing them with glycine residues. The C. jejuni H25G/H37G substituted variant showed reduced iron binding and ferroxidase activities in comparison with wt Dps, while DNA-binding activity remained unaffected. We also found that both CjDps wt and CjDps H25G/H37G were able to bind manganese atoms. These results indicate that the H25 and H37 residues at the ferroxidase centre of C. jejuni Dps are not strictly required for metal binding and oxidation. PMID- 26555737 TI - Diagnostic testing for Clostridium difficile in Italian microbiological laboratories. AB - A laboratory diagnosis survey of Clostridium difficile infection (CDI) was performed in Italy in 2012-2013. Questionnaires from 278 healthcare settings from 15 regions of Italy were collected and analysed. Eighty seven percent of the laboratories declared to routinely perform CDI diagnosis, 99% of them only after the clinician's request. Among the 216 laboratories providing information on the size of the hospitals in which they were located, 65 had more than 500 beds (large hospitals), while 151 had less than 500 beds (small hospitals). The average percentage of positive tests for C. difficile toxins was 12.2%. Almost half of the laboratories (42%) used immunoenzymatic assay (EIA) for Tox A/B as a stand-alone method, while only 34% used an algorithm for CDI as indicated by the European guidelines. A low percentage of laboratories performed molecular assays or C. difficile culture, 25% and 29%, respectively. Most laboratories (161/278) declared to type C. difficile strains, the majority in collaboration with a reference laboratory. Among the 103 C. difficile clinical isolates collected during the study, 31 different PCR-ribotypes were identified. PCR-ribotype 356/607 (27%) was predominant, followed by 018 (12%). These two PCR-ribotypes show 87.5% of similarity in ribotyping profile. PCR-ribotypes 027 and 078 represented 8% and 4% of the strains, respectively. Four PCR-ribotypes (027, 033, 078 and 126) were positive for the binary toxin CDT. In particular, PCR-ribotype 033 produces only CDT, and it has recently been associated with symptomatic cases. The majority of strains were multidrug resistant. In particular, all strains PCR-ribotypes 356/607 and 018 were resistant to moxifloxacin, rifampicin, erythromycin and clindamycin. The results obtained highlight the need to raise awareness to the microbiological diagnosis of CDI among clinicians and to implement and harmonize diagnostic methods for CDI in Italian laboratories in the perspective of a future national surveillance. PMID- 26555738 TI - Slip resistance of winter footwear on snow and ice measured using maximum achievable incline. AB - Protective footwear is necessary for preventing injurious slips and falls in winter conditions. Valid methods for assessing footwear slip resistance on winter surfaces are needed in order to evaluate footwear and outsole designs. The purpose of this study was to utilise a method of testing winter footwear that was ecologically valid in terms of involving actual human testers walking on realistic winter surfaces to produce objective measures of slip resistance. During the experiment, eight participants tested six styles of footwear on wet ice, on dry ice, and on dry ice after walking over soft snow. Slip resistance was measured by determining the maximum incline angles participants were able to walk up and down in each footwear-surface combination. The results indicated that testing on a variety of surfaces is necessary for establishing winter footwear performance and that standard mechanical bench tests for footwear slip resistance do not adequately reflect actual performance. Practitioner Summary: Existing standardised methods for measuring footwear slip resistance lack validation on winter surfaces. By determining the maximum inclines participants could walk up and down slopes of wet ice, dry ice, and ice with snow, in a range of footwear, an ecologically valid test for measuring winter footwear performance was established. PMID- 26555739 TI - Modular Access to the Stereoisomers of Fused Bicyclic Azepines: Rhodium-Catalyzed Intramolecular Stereospecific Hetero-[5+2] Cycloaddition of Vinyl Aziridines and Alkenes. AB - The first rhodium-catalyzed intramolecular hetero-[5+2] cycloaddition reaction of vinyl aziridines and alkenes was realized, wherein both internal and terminal alkenes were applicable. With this method, a variety of unique substituted chiral fused bicyclic azepines, bearing multiple contiguous stereogenic centers, were facilely accessed in a straightforward, high-yielding, and highly stereoselective manner under mild reaction conditions. Notably, the E/Z geometry of the C?C bonds in the vinyl aziridine-alkene substrates impact the cis/trans stereochemistry of the cycloadducts and up to six stereoisomers could be delivered. PMID- 26555740 TI - ENDOTHELIUM-DERIVED INHIBITORS EFFICIENTLY ATTENUATE THE AGGREGATION AND ADHESION RESPONSES OF REFRIGERATED PLATELETS. AB - Refrigeration of platelets (4 degrees C) provides the possibility of improving transfusion practice over the current standard-of-care, room temperature (RT) storage. However, the increased level of platelet activation observed at 4 degrees C in vitro is cause for concern of uncontrolled thrombosis in vivo. In this study, we assessed the safety of 4 degrees C-stored platelets by evaluating their response to physiologic inhibitors prostacyclin (PGI2) and nitric oxide (NO). Apheresis platelets were collected from healthy donors (n = 4) and tested on Day 1 (fresh) or Day 5 (RT- and 4 degrees C-stored) after treatment with PGI2 and NO or not for: thrombin generation; factor V (FV) activity; intracellular free calcium, cAMP and cGMP; ATP release; TRAP-induced activation; aggregation to ADP, collagen, and TRAP, and adhesion to collagen under arterial flow. Data were analyzed using two-way ANOVA and post-hoc Tukey test for multiple comparisons, with significance set at P < 0.05. Treatment with inhibitors increased intracellular cAMP and cGMP levels in fresh and stored platelets. Thrombin generation was significantly accelerated in stored platelets consistent with increased factor V levels, PS exposure, CD62P expression, intracellular free calcium, and ATP release. While treatment with inhibitors did not attenuate thrombin generation in stored platelets, activation, aggregation, and adhesion responses were inhibited by both PGI2 and NO in 4 degrees C-stored platelets. In contrast, though RT-stored platelets were activated, they did not adhere or aggregate in response to agonists. Thus, refrigerated platelets maintain their intracellular machinery, are responsive to agonists and platelet function inhibitors, and perform hemostatically better than RT-stored platelets. PMID- 26555741 TI - THE PROTECTIVE ROLE OF CURCUMIN IN ZYMOSAN-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME IN MICE. AB - AIM: Multiple Organ Dysfunction Syndrome (MODS) is characterized as progressive and uncontrolled inflammatory response which involves activation of inflammatory cascades, cytokines release, and endothelial dysfunction, leading to deterioration of several organ functions. Curcumin is a natural polyphenol related to the yellow color of turmeric and has been reported to exert an anti inflammatory, anti-oxidative, and anti-tumor effect. We conducted the study to investigate the effects of curcumin in non-septic MODS caused by zymosan in mice model. METHOD: The mice were randomly allocated into five groups (six mice per group): control group (treated with physiological saline, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), Curcumin group (200 mg/kg, suspended in DMSO, in a final volume of 0.1 mL, used for 3 days daily before and 1 h after physiological saline treatment), Zymosan+DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after zymosan treatment) and Zymosan+ Curcumin group (treated with curcumin, suspended in DMSO at a dose of 0.1 mL daily for 3 days before and 1 h after zymosan treatment).Mice in groups were sacrificed, and then the blood and tissues were collected to evaluate the severity of acute peritonitis, tissue histopathological changes, NO formation, oxidative stress, PMN infiltration, cytokines production, organ function, and NF-kappaB activation 18 h after when zymosan or physiological saline was injected. In another set of experiments, the mice were also grouped (20 mice per group) for monitoring the loss of body weight and mortality for 7 days after zymosan or physiological saline administration. RESULTS: Curcumin induces a significant reduction of the volume exudate and the neutrophil infiltration. It also could exhibit an outstanding protective effect against histopathological injury by decreasing the NO formation, oxidative stress, cytokines production, and infiltration of inflammatory cells. The organ function is also improved by administration of curcumin. Moreover, the activation of NF-kappaB is attenuated by curcumin in the MODS mice model, suggesting that curcumin attenuated the zymosan-induced MODS via inhibiting the expression of NF kappaB possibly. In addition, curcumin-treated mice were shown to alleviate the severity of MODS characterized by a minor systemic toxicity, less body weight loss, and lower mortality caused by zymosan administration. CONCLUSION: Curcumin attenuates zymosan-induced MODS. PMID- 26555742 TI - CHANGES IN SUBLINGUAL MICROCIRCULATION IS CLOSELY RELATED WITH THAT OF BULBAR CONJUNCTIVAL MICROCIRCULATION IN A RAT MODEL OF CARDIAC ARREST. AB - Following successful resuscitation, a significantly impaired microcirculation has been identified. The severity of the impairment of microcirculation is closely related to that of vital organ dysfunction. Sublingual microcirculation is a traditional site for the measurement of tissue perfusion. In the present study, we investigated the bulbar conjunctival microcirculatory alterations following CPR and its relationship with the changes of sublingual microcirculation in a rat model of cardiac arrest.Male Sprague-Dawley rats (450-550 g) were utilized. Ventricular fibrillation was induced and untreated for 8 min followed by 8 min of CPR. Sublingual and bulbar conjunctival microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline, 30 min, 1, 2, 4, and 8 h post-resuscitation. Both perfused vessel density (PVD) and microcirculatory flow index (MFI) were recorded.The post-resuscitation PVD and MFI were significantly decreased in both sublingual and bulbar conjunctival sites. Sublingual PVD decreased from baseline of 5.9 +/- 0.3 to 3.1 +/- 0.4 n/mm at 30 min post-resuscitation and MFI from 3.0 +/- 0.0 to 1.5 +/- 0.3 (both P < 0.05 vs. baseline). Bulbar conjunctival PVD was significantly reduced from baseline of 6.5 +/- 0.6 to 3.9 +/- 0.5 n/mm at 30 min post-resuscitation and MFI from 3.0 +/- 0.0 to 1.2 +/- 0.4 (both P < 0.05 vs. baseline). PVD, MFI, and cardiac function did not change significantly from the 30-min measurements in the surviving rats throughout the remainder of the study (both P > 0.05 vs. 30-min post-resuscitation). The decreases in sublingual microcirculatory blood flow were closely correlated with the reductions of bulbar conjunctival microcirculatory blood flow (PVD: r = 0.87, P < 0.05; MFI: r = 0.92, P < 0.05). Myocardial function was significantly impaired in all animals after resuscitation when compared with baseline values (P < 0.05). The impairments of both sublingual and bulbar conjunctival microcirculation were significantly correlated with the impairment of myocardial function.In the rat model of cardiac arrest, the changes in sublingual microcirculatory blood flow are closely correlated with that of bulbar conjunctival microcirculatory blood flow after successful resuscitation. The changes are correlated with the severity of post-resuscitation myocardial dysfunction. Our study testified sublingual site could be substituted by bulbar conjunctival at least in the rat model of cardiac arrest. The measurement of conjunctival microcirculation may provide an accessible and convenient option as sublingual site for monitoring microcirculation in humans. PMID- 26555743 TI - PLASMA HEME OXYGENASE-1 IN PATIENTS RESUSCITATED FROM OUT-OF-HOSPITAL CARDIAC ARREST. AB - Heme oxygenase-1 (HO-1) is an enzyme induced by hypoxia and reperfusion injury, and is associated with organ dysfunction in critically ill patients. Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are subjected to hypoxemia, brain injury, and organ dysfunction. Accordingly, we studied HO-1 among these patients. A total of 143 OHCA patients resuscitated from a shockable initial rhythm and admitted to an ICU were included, with plasma HO-1 measured at ICU admission and at 24 h. We analyzed the associations between plasma HO-1 and time to return of spontaneous circulation (ROSC), 90-day mortality, and 12-month Cerebral Performance Category (CPC). HO-1 plasma concentrations were higher after OHCA compared with controls. HO-1 concentrations at admission and on day 1 associated with ROSC (P = 0.002 to P = 0.003). Admission and day 1 HO-1 plasma concentrations were higher in 90-day non-survivors than in survivors (P = 0.017, 0.026). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (P = 0.024). Admission plasma HO-1 levels had an AUC of 0.623 to predict 90-day mortality and an AUC of 0.611 to predict CPC 3 to 5. In conclusion, we found that higher HO-1 plasma levels are associated with longer ROSC and poor long-term outcome. PMID- 26555744 TI - REMOTE ISCHEMIC CONDITIONING INFLUENCES MITOCHONDRIAL DYNAMICS. AB - Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission. Interventions that decrease mitochondrial fission or increase mitochondrial fusion have been associated with reduced I/R injury. However, whether RIPC influences mitochondrial dynamics or not has yet to be ascertained.We sought to determine the role played by mitochondrial dynamics in RIPC-induced cardioprotection. Male adult rats exposed in vivo to myocardial I/R were assigned to one of two groups, either undergoing 40 min of myocardial ischemia followed by 120 min of reperfusion (MI group) or four 5-min cycles of limb ischemia interspersed by 5 min of limb reperfusion, immediately prior to myocardial ischemia and 120 min of reperfusion (MI+RIPC group). After reperfusion, infarct size was assessed and myocardial tissue was analyzed by Western blot and electron microscopy. RIPC induced smaller infarct size (-28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology. These findings suggest that mitochondrial dynamics play a role in the mechanisms of RIPC-induced cardioprotection. PMID- 26555745 TI - Endoscopic instrument tracking for surgical simulation training in a controlled environment via a camera and a planar mirror. AB - Minimally Invasive Surgery (MIS) has many advantages over traditional procedures and thus training with MIS tools via computer simulations has received much attention. These tools are generally grouped into two major categories: Physical training-boxes, and Computer vision/Virtual Reality (VR) tools. In this study, a computer vision based simulator is proposed which uses a training box that is composed of a single camera and a planar mirror. Occlusions are appropriately handled by the use of the epipoint geometry. The average 3D positional error was 0.96mm (+/-0.44mm) at 1280*960 resolution, and 1.18mm (+/-0.52mm) at 320*240. So, the error is minimally affected as the resolution decreases. The proposed method has some advantages over relevant literature methods, such as an improved accuracy (approximately 60%) even at low resolutions with a low processing time (approximately 30%). Therefore, the proposed method appears as a promising and low cost (approximately 50%) alternative for computer vision based MIS training tools. PMID- 26555746 TI - A novel fuzzy logic-based image steganography method to ensure medical data security. AB - This study aims to secure medical data by combining them into one file format using steganographic methods. The electroencephalogram (EEG) is selected as hidden data, and magnetic resonance (MR) images are also used as the cover image. In addition to the EEG, the message is composed of the doctor's comments and patient information in the file header of images. Two new image steganography methods that are based on fuzzy-logic and similarity are proposed to select the non-sequential least significant bits (LSB) of image pixels. The similarity values of the gray levels in the pixels are used to hide the message. The message is secured to prevent attacks by using lossless compression and symmetric encryption algorithms. The performance of stego image quality is measured by mean square of error (MSE), peak signal-to-noise ratio (PSNR), structural similarity measure (SSIM), universal quality index (UQI), and correlation coefficient (R). According to the obtained result, the proposed method ensures the confidentiality of the patient information, and increases data repository and transmission capacity of both MR images and EEG signals. PMID- 26555747 TI - Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection. AB - OBJECTIVE: Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting. METHODS: Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months. RESULTS: In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection. CONCLUSION: Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results. PMID- 26555748 TI - Partial Dedifferentiation of Murine Radial Glia-Type Neural Stem Cells by Brn2 and c-Myc Yields Early Neuroepithelial Progenitors. AB - Direct cell conversion developed into an important paradigm for generating cells with enhanced differentiation capability. We combined a transcription-factor based cell fate conversion strategy with the use of pharmacological compounds to derive early neuroepithelial progenitor cells from developmentally more restricted radial glia-type neural stem cells. By combining the small molecules CHIR99021, Tranylcypromine, SB431542 and valproic acid with viral transduction of the transcription factor c-Myc and the POU domain transcription factor Brn2, we dedifferentiated radial glia-type neural stem cells into an early neuroepithelial progenitor cell state within 6 days. Reverse transcription PCR analyses showed a rapid down-regulation of the radial glia markers Olig2 and Vimentin during conversion, whereas the neuroepithelial markers Dach1 and Sox1 were fastly up regulated. Furthermore, a switch from N-Cadherin to E-Cadherin indicates a mesenchymal-to-epithelial transition. The differentiation of cells converted by Brn2/c-Myc yielded smooth muscle actin- and Peripherin-positive cells in addition to the neuronal marker TUJ1 and cells that are positive for the glial marker GFAP. This differentiation potential suggests that the applied reprogramming strategy induced an early neuroepithelial cell population, which might resemble cells of the neural border or even more primitive neuroepithelial cells. PMID- 26555749 TI - Efficient Genome Manipulation by Variants of Site-Specific Recombinases R and TD. AB - Genome engineering benefits from the availability of DNA modifying enzymes that have different target specificities and have optimized performance in different cell types. This variety of site-specific enzymes can be used to develop complex genome engineering applications at multiple loci. Although eight yeast site specific tyrosine recombinases are known, only Flp is actively used in genome engineering. To expand the pool of the yeast site-specific tyrosine recombinases capable of mediating genome manipulations in mammalian cells, we engineered and analyzed variants of two tyrosine recombinases: R and TD. The activity of the evolved variants, unlike the activity of the native R and TD recombinases, is suitable for genome engineering in Escherichia coli and mammalian cells. Unexpectedly, we found that R recombinase benefits from the shortening of its C terminus. We also found that the activity of wild-type R can be modulated by its non-consensus "head" sequence but this modulation became not apparent in the evolved R variants. The engineered recombinase variants were found to be active in all recombination reactions tested: excision, integration, and dual recombinase-mediated cassette exchange. The analysis of the latter reaction catalyzed by the R/TD recombinase pair shows that the condition supporting the most efficient replacement reaction favors efficient TD-mediated integration reaction while favoring efficient R-mediated integration and deletion reactions. PMID- 26555751 TI - Crystal Structure Analysis of Wild Type and Fast Hydrolyzing Mutant of EhRabX3, a Tandem Ras Superfamily GTPase from Entamoeba histolytica. AB - The enteric protozoan parasite, Entamoeba histolytica, is the causative agent of amoebic dysentery, liver abscess and colitis in human. Vesicular trafficking plays a key role in the survival and virulence of the protozoan and is regulated by various Rab GTPases. EhRabX3 is a catalytically inefficient amoebic Rab protein, which is unique among the eukaryotic Ras superfamily by virtue of its tandem domain organization. Here, we report the crystal structures of GDP-bound fast hydrolyzing mutant (V71A/K73Q) and GTP-bound wild type EhRabX3 at 3.1 and 2.8A resolutions, respectively. Though both G-domains possess "phosphate binding loop containing nucleoside triphosphate hydrolases fold", only the N-terminal domain binds to guanine nucleotide. The relative orientation of the N-terminal domain and C-terminal domain is stabilized by numerous inter-domain interactions. Compared to other Ras superfamily members, both the GTPase domains displayed large deviation in switch II perhaps due to non-conservative substitutions in this region. As a result, entire switch II is restructured and moved away from the nucleotide binding pocket, providing a rationale for the diminished GTPase activity of EhRabX3. The N-terminal GTPase domain possesses unusually large number of cysteine residues. X-ray crystal structure of the fast hydrolyzing mutant of EhRabX3 revealed that C39 and C163 formed an intra-molecular disulfide bond. Subsequent mutational and biochemical studies suggest that C39 and C163 are critical for maintaining the structural integrity and function of EhRabX3. Structure-guided functional investigation of cysteine mutants could provide the physiological implications of the disulfide bond and could allow us to design potential inhibitors for the better treatment of intestinal amebiasis. PMID- 26555752 TI - Relationship between the extent of dissection and platelet activation in acute aortic dissection. AB - BACKGROUND: The extent of acute aortic dissection (AAD) was correlated with inflammation positively. On the other side, inflammation was negatively correlated with mean platelet volume (MPV), which can reflect platelet (PLT) activation. The aim of this study was to clarify the relationship between the extent of dissection and PLT activation. METHODS: Between February 2010 and October 2013, 147 patients with acute aortic dissection (AAD) were divided into Group 1 (Stanford A, n = 59) and Group 2 (Stanford B, n = 88). Platelet count, MPV and platelet size distribution width (PDW) were measured to assess PLT activation. Additionally, the severity of inflammation was assessed via serum C reactive protein (CRP), white blood cell (WBC) count and the neutrophil percent (Neut%). Computerized tomography (CT) was employed to analyze the extent of AAD. Volume tear index (VTI) was calculated as the false lumen (FL) volume divided by body surface area (BSA). RESULTS: PLT count was significantly lower in group 1 than in group 2 (137.24 +/- 31.04 * 10(9)/L vs 171.43 +/- 27.57 * 10(9)/L, P < 0.001). The MPV/PLT ratio and PDW were significantly higher in the group 1 respectively(0.08 +/- 0.02 vs 0.06 +/- 0.02, P < 0.001; 22.65 +/- 1.87 fl vs 20.69 +/- 1.97 fl, P < 0.001). The CRP was significantly higher in group 1 than in group 2 (36.40 +/- 8.89 mg/L vs 28.97 +/- 8.48 mg/L, P < 0.001). VTI was significantly higher in group 1 than in group 2 (250.12 +/- 27.82 vs 198.79 +/- 24.52, P < 0.001). There was a significant negative correlation between VTI and PLT count (r = -0.673, P < 0.001), CRP and PLT count (r = -0.640, P < 0.001), respectively. There was a significant positive correlation between VTI and CRP (r = 0.670, P < 0.001), VTI and PDW (r = 0.601, P < 0.001), respectively. CONCLUSIONS: PLT activation and inflammation in AAD appear to be closely correlated with the extent of dissection, which possibly induced by the tear of aortic wall. Elimination of the false lumen is the goal of traditional surgery. Suppression of the PLT activation might be future targets of therapy in the prevention of systemic inflammation in AAD patients. PMID- 26555750 TI - Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines. AB - Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. PMID- 26555753 TI - Sodium butyrate down-regulates tristetraprolin-mediated cyclin B1 expression independent of the formation of processing bodies. AB - Butyrate regulates multiple host cellular events including the cell cycle; however, little is known about the molecular mechanism by which butyrate induces a global down-regulation of the expression of genes associated with the cell cycle. Here, we demonstrate that treating HEK293T cells and the non-small-cell lung cancer cell line A549 with a high concentration of sodium butyrate reduces cyclin B1 expression. The underlying mechanism is related to the destabilization of its mRNA by tristetraprolin, which is up-regulated in response to sodium butyrate. Specifically, the sodium butyrate stimulation reduces the mRNA and protein expression of cyclin B1 and, conversely, upregulates tristetraprolin expression. Importantly, the overexpression of tristetraprolin in HEK293T decreases the mRNA and protein expression of cyclin B1; in contrast, knockdown of tristetraprolin mediated by small interfering RNA increases its expression in response to sodium butyrate treatment for both HEK293T and A549 cells. Furthermore, results from luciferase reporter assays and RNA immunoprecipitation indicate that sodium butyrate accelerates 3' UTR-dependent cyclin B1 decay by enhancing the binding of tristetraprolin to the 3' untranslated region of cyclin B1. Surprisingly, the overexpression of tristetraprolin prevents the formation of processing bodies, and the siRNA-mediated silencing of EDC4 does not restore the sodium butyrate-induced reduction of cyclin B1 expression. Thus, we confirm that NaBu regulates ZFP36-mediated cyclin B1 expression in a manner that is independent of the formation of P-bodies. The above findings disclose a novel mechanism of sodium butyrate-mediated gene expression regulation and might benefit its application in tumor treatment. PMID- 26555754 TI - Blue light emitting diode induces apoptosis in lymphoid cells by stimulating autophagy. AB - The present study was performed to examine the induction of apoptotic cell death and autophagy by blue LED irradiation, and the contribution of autophagy to apoptosis in B cell lymphoma A20 and RAMOS cells exposed to blue LED. Irradiation with blue LED reduced cell viability and induced apoptotic cell death, as indicated by exposure of phosphatidylserine on the plasma outside membrane and fragmentation of DNA. Furthermore, the mitochondrial membrane potential increased, and apoptotic proteins (PARP, caspase 3, Bax, and bcl-2) were observed. In addition, the level of intracellular superoxide anion (O2(-)) gradually increased. Interestingly the formation of autophagosomes and level of LC3-II were increased in blue LED-irradiated A20 and RAMOS cells, but inhibited after pretreatment with 3-methyladenine (3-MA), widely used as an autophagy inhibitor. Inhibition of the autophagic process by pretreatment with 3-MA blocked blue LED irradiation-induced caspase-3 activation. Moreover, a significant reduction of both the early and late phases of apoptosis after transfection with ATG5 and beclin 1 siRNAs was shown by the annexin V/PI staining, indicating a crucial role of autophagy in blue LED-induced apoptosis in cells. Additionally, the survival rate of mice irradiated with blue LED after injection with A20 cells increased compared to the control group. Our data demonstrate that blue LED irradiation induces apoptosis via the mitochondrial-mediated pathway, in conjunction with autophagy. Further studies are needed to elucidate the precise mechanism of blue LED-induced immune cell death. PMID- 26555755 TI - Fractional Brownian motion and multivariate-t models for longitudinal biomedical data, with application to CD4 counts in HIV-positive patients. AB - Longitudinal data are widely analysed using linear mixed models, with 'random slopes' models particularly common. However, when modelling, for example, longitudinal pre-treatment CD4 cell counts in HIV-positive patients, the incorporation of non-stationary stochastic processes such as Brownian motion has been shown to lead to a more biologically plausible model and a substantial improvement in model fit. In this article, we propose two further extensions. Firstly, we propose the addition of a fractional Brownian motion component, and secondly, we generalise the model to follow a multivariate-t distribution. These extensions are biologically plausible, and each demonstrated substantially improved fit on application to example data from the Concerted Action on SeroConversion to AIDS and Death in Europe study. We also propose novel procedures for residual diagnostic plots that allow such models to be assessed. Cohorts of patients were simulated from the previously reported and newly developed models in order to evaluate differences in predictions made for the timing of treatment initiation under different clinical management strategies. A further simulation study was performed to demonstrate the substantial biases in parameter estimates of the mean slope of CD4 decline with time that can occur when random slopes models are applied in the presence of censoring because of treatment initiation, with the degree of bias found to depend strongly on the treatment initiation rule applied. Our findings indicate that researchers should consider more complex and flexible models for the analysis of longitudinal biomarker data, particularly when there are substantial missing data, and that the parameter estimates from random slopes models must be interpreted with caution. PMID- 26555756 TI - Rapid decrement in the effects of the Ponzo display dissociates action and perception. AB - It has been demonstrated that pictorial illusions have a smaller influence on grasping than they do on perceptual judgments. Yet to date this work has not considered the reduced influence of an illusion as it is measured repeatedly. Here we studied this decrement in the context of a Ponzo illusion to further characterize the dissociation between vision for perception and for action. Participants first manually estimated the lengths of single targets in a Ponzo display with their thumb and index finger, then actually grasped these targets in another series of trials, and then manually estimated the target lengths again in a final set of trials. The results showed that although the perceptual estimates and grasp apertures were equally sensitive to real differences in target length on the initial trials, only the perceptual estimates remained biased by the illusion over repeated measurements. In contrast, the illusion's effect on the grasps decreased rapidly, vanishing entirely after only a few trials. Interestingly, a closer examination of the grasp data revealed that this initial effect was driven largely by undersizing the grip aperture for the display configuration in which the target was positioned between the diverging background lines (i.e., when the targets appeared to be shorter than they really were). This asymmetry between grasping apparently shorter and longer targets suggests that the sensorimotor system may initially treat the edges of the configuration as obstacles to be avoided. This finding highlights the sensorimotor system's ability to rapidly update motor programs through error feedback, manifesting as an immunity to the effects of illusion displays even after only a few trials. PMID- 26555757 TI - Integrating SLAM with existing evidence: Comment on Walker and Hickok (2015). AB - Walker and Hickok (Psychonomic Bulletin & Review doi:10.3758/s13423-015-0903-7, 2015) used simulations to compare a novel proposal, the semantic-lexical-auditory motor model (SLAM), to an existing account of speech production, the two-step interactive account (TSIA; Foygel & Dell, Journal of Memory and Language, 43:182 216, doi:10.1006/jmla.2000.2716, 2000). This commentary critically examines their assessment of SLAM. The cases in which SLAM outperforms TSIA largely reflect SLAM's ability to (poorly) approximate an existing theory of speech production incorporating two stages of phonological processing (the lexical + postlexical account). The fact that SLAM and TSIA can exhibit equivalent fits to the overall response distribution of a set of aphasic patients is unsurprising, since previous work has shown that overall response distributions do not reliably discriminate theoretical alternatives. Finally, SLAM inherits issues associated with TSIA's assumption of strong feedback between levels of representation. This suggests that SLAM does not represent an advance over existing theories of speech production. PMID- 26555758 TI - Height outcome of short children with hypochondroplasia after recombinant human growth hormone treatment: a meta-analysis. AB - Hypochondroplasia (HCH) is a genetic skeletal dysplasia, characterized by rhizomelic short height (Ht) with facial dysmorphology and lumbar hyperlordosis. Albeit there are concerns that HCH children may not achieve optimal long-term outcome in response to recombinant human growth hormone (rhGH), anecdotal experiences suggested at least short-term Ht improvement. After thorough search of published studies, meta-analysis of rhGH use in HCH children was performed. In 113 HCH children, rhGH administration (median 0.25 mg/kg/week) progressively improved Ht pattern with 12 months catch-up growth (p < 0.0001). Then, Ht improvement resulted constant until 36 months (p < 0.0001), but stature remained subnormal. While bone age chronologically progressed, no serious adverse events were reported. In conclusion, our meta-analysis indicates that rhGH treatment progressively improved Ht outcome of HCH subjects. PMID- 26555759 TI - An Editor's farewell! PMID- 26555761 TI - Comprehensive Infrared Study of Tetryl, Dinitrotoluene, and Trinitrotoluene Compounds. AB - The present work describes an experimental and theoretical study of energetic materials used for detecting explosives in order to prevent terrorist actions, as well as for de-mining projects. Particular attention was devoted to examining the infrared absorption spectroscopy of classic explosives in order to create a useful mobile apparatus for on-field detection of explosives. This paper reports the vibrational absorption spectra of tetryl, dinitrotoluene, and trinitrotoluene molecules approached using two different spectroscopic techniques, Fourier transform infrared spectroscopy (FT-IR) and laser photoacoustic spectroscopy (LPAS). Diffuse reflectance Fourier transform infrared spectra of all samples were analyzed in a very wide spectral range (400-7500 cm(-1)) showing for the first time the existence of weak absorption bands attributable to overtones or combination bands, while laser photoacoustic spectroscopy spectra have been investigated in the fingerprint region of organic compounds that share the CO2 laser emission range (~920-1100 cm(-1)). The Fourier transform infrared spectra of both matrix isolated dinitrotoluenes have been also investigated. The theoretical treatment of tetryl is reported for the first time. PMID- 26555760 TI - Real-time functional characterization of cationic amino acid transporters using a new FRET sensor. AB - L-arginine is a semi-essential amino acid that serves as precursor for the production of urea, nitric oxide (NO), polyamines, and other biologically important metabolites. Hence, a fast and reliable assessment of its intracellular concentration changes is highly desirable. Here, we report on a genetically encoded Forster resonance energy transfer (FRET)-based arginine nanosensor that employs the arginine repressor/activator ahrC gene from Bacillus subtilis. This new nanosensor was expressed in HEK293T cells, and experiments with cell lysate showed that it binds L-arginine with high specificity and with a K d of ~177 MUM. Live imaging experiments showed that the nanosensor was expressed throughout the cytoplasm and displayed a half maximal FRET increase at an extracellular L arginine concentration of ~22 MUM. By expressing the nanosensor together with SLC7A1, SLC7A2B, or SLC7A3 cationic amino acid transporters (CAT1-3), it was shown that L-arginine was imported at a similar rate via SLC7A1 and SLC7A2B and slower via SLC7A3. In contrast, upon withdrawal of extracellular L-arginine, intracellular levels decreased as fast in SLC7A3-expressing cells compared with SLC7A1, but the efflux was slower via SLC7A2B. SLC7A4 (CAT4) could not be convincingly shown to transport L-arginine. We also demonstrated the impact of membrane potential on L-arginine transport and showed that physiological concentrations of symmetrical and asymmetrical dimethylarginine do not significantly interfere with L-arginine transport through SLC7A1. Our results demonstrate that the FRET nanosensor can be used to assess L-arginine transport through plasma membrane in real time. PMID- 26555762 TI - Submaximal cardiopulmonary thresholds on a robotics-assisted tilt table, a cycle and a treadmill: a comparative analysis. AB - BACKGROUND: The robotics-assisted tilt table (RATT), including actuators for tilting and cyclical leg movement, is used for rehabilitation of severely disabled neurological patients. Following further engineering development of the system, i.e. the addition of force sensors and visual bio-feedback, patients can actively participate in exercise testing and training on the device. Peak cardiopulmonary performance parameters were previously investigated, but it also important to compare submaximal parameters with standard devices. The aim of this study was to evaluate the feasibility of the RATT for estimation of submaximal exercise thresholds by comparison with a cycle ergometer and a treadmill. METHODS: 17 healthy subjects randomly performed six maximal individualized incremental exercise tests, with two tests on each of the three exercise modalities. The ventilatory anaerobic threshold (VAT) and respiratory compensation point (RCP) were determined from breath-by-breath data. RESULTS: VAT and RCP on the RATT were lower than the cycle ergometer and the treadmill: oxygen uptake (V'O2) at VAT was [mean (SD)] 1.2 (0.3), 1.5 (0.4) and 1.6 (0.5) L/min, respectively (p < 0.001); V'O2 at RCP was 1.7 (0.4), 2.3 (0.8) and 2.6 (0.9) L/min, respectively (p = 0.001). High correlations for VAT and RCP were found between the RATT vs the cycle ergometer and RATT vs the treadmill (R on the range 0.69-0.80). VAT and RCP demonstrated excellent test-retest reliability for all three devices (ICC from 0.81 to 0.98). Mean differences between the test and retest values on each device were close to zero. The ventilatory equivalent for O2 at VAT for the RATT and cycle ergometer were similar and both were higher than the treadmill. The ventilatory equivalent for CO2 at RCP was similar for all devices. Ventilatory equivalent parameters demonstrated fair-to-excellent reliability and repeatability. CONCLUSIONS: It is feasible to use the RATT for estimation of submaximal exercise thresholds: VAT and RCP on the RATT were lower than the cycle ergometer and the treadmill, but there were high correlations between the RATT vs the cycle ergometer and vs the treadmill. Repeatability and test-retest reliability of all submaximal threshold parameters from the RATT were comparable to those of standard devices. PMID- 26555763 TI - Transferring Xenogenic Mitochondria Provides Neural Protection Against Ischemic Stress in Ischemic Rat Brains. AB - Transferring exogenous mitochondria has therapeutic effects on damaged heart, liver, and lung tissues. Whether this protective effect requires the symbiosis of exogenous mitochondria in host cells remains unknown. Here xenogenic mitochondria derived from a hamster cell line were applied to ischemic rat brains and rat primary cortical neurons. Isolated hamster mitochondria, either through local intracerebral or systemic intra-arterial injection, significantly restored the motor performance of brain-ischemic rats. The brain infarct area and neuronal cell death were both attenuated by the exogenous mitochondria. Although internalized mitochondria could be observed in neurons and astrocytes, the low efficacy of mitochondrial internalization could not completely account for the high rate of rescue of the treated neural cells. We further illustrated that disrupting electron transport or ATPase synthase in mitochondria significantly attenuated the protective effect, suggesting that intact respiratory activity is essential for the mitochondrial potency on neural protection. These results emphasize that nonsymbiotic extracellular mitochondria can provide an effective cell defense against acute injurious ischemic stress in the central nervous system. PMID- 26555764 TI - Research and Evaluations of the Health Aspects of Disasters, Part V: Epidemiological Disaster Research. AB - Studies of the health aspect of disasters focus either on the epidemiology of disasters to define the causes and the progression from a hazard to a disaster, or the evaluations of interventions provided during any phase of a disaster. Epidemiological disaster research studies are undertaken for the purposes of: (1) understanding the mechanisms by which hazards evolve into a disaster; (2) determining ways to mitigate the risk(s) that a specific hazard will progress into a disaster; (3) predicting the likely damages and needs of the population-at risk for an event; and (4) identifying potential measures to increase the resilience of a community to future events. Epidemiological disaster research utilizes the Conceptual, Temporal, and Societal Frameworks to define what occurs when a hazard manifests as an event that causes a disaster. The findings from such studies should suggest interventions that could augment the absorbing, buffering, or/and response capacities to lessen the probability of similar damages occurring from the next event. Ultimately, the use of these Frameworks in studying the health aspects of a disaster will help define what to expect in a specific setting and the standards and best practices upon which education, training, competencies, performance, and professionalization will be built. PMID- 26555765 TI - PET measurement of brain acetylcholinesterase activities in cortex and subcortical areas. PMID- 26555766 TI - Effect of age and sex on bone markers in Chlorocebus aethiops raised in captivity. AB - BACKGROUND: The objective was to evaluate the procollagen type I N-propeptide (PINP), osteocalcin (OC), beta-crosslaps (beta-CTX), and parathyroid hormone (PTH) in relation to age and sex of Chlorocebus aethiops in captivity. METHODS: Seventy-three monkeys were divided into four age groups: AG1 (juvenile); AG2 (young adult); AG3 (adult); and AG4 (senile). An electrochemiluminescence immunoassay with an Elecsys 2010 analyzer was used to determine the serum markers of bone. RESULTS AND CONCLUSIONS: Sex did not influence the results of the markers. However, the variables PINP, OC, and beta-CTX were negatively correlated with age (r = -0.643; r = -0.711; r = -0.488; P < 0.001, respectively), and PTH was correlated positively with age (r = 0.418, P < 0.001). The data obtained can be used as biomarkers of bone metabolism reference intervals in healthy C. aethiops in captivity. PMID- 26555767 TI - Differential Control by 5-HT and 5-HT1A, 2A, 2C Receptors of Phasic and Tonic GABAA Inhibition in the Visual Thalamus. PMID- 26555768 TI - Translational plant biology. PMID- 26555769 TI - An Optimized Method for Isolating and Expanding Invariant Natural Killer T Cells from Mouse Spleen. AB - The ability to rapidly secrete cytokines upon stimulation is a functional characteristic of the invariant natural killer T (iNKT) cell lineage. iNKT cells are therefore characterized as an innate T cell population capable of activating and steering adaptive immune responses. The development of improved techniques for the culture and expansion of murine iNKT cells facilitates the study of iNKT cell biology in in vitro and in vivo model systems. Here we describe an optimized procedure for the isolation and expansion of murine splenic iNKT cells. Spleens from C57Bl/6 mice are removed, dissected and strained and the resulting cellular suspension is layered over density gradient media. Following centrifugation, splenic mononuclear cells (MNCs) are collected and CD5-positive (CD5(+)) lymphocytes are enriched for using magnetic beads. iNKT cells within the CD5(+) fraction are subsequently stained with alphaGalCer-loaded CD1d tetramer and purified by fluorescence activated cell sorting (FACS). FACS sorted iNKT cells are then initially cultured in vitro using a combination of recombinant murine cytokines and plate-bound T cell receptor (TCR) stimuli before being expanded in the presence of murine recombinant IL-7. Using this technique, approximately 10(8) iNKT cells can be generated within 18-20 days of culture, after which they can be used for functional assays in vitro, or for in vivo transfer experiments in mice. PMID- 26555770 TI - New Tricks for Old Proteins: Single Mutations in a Nonenzymatic Protein Give Rise to Various Enzymatic Activities. AB - Design of a new catalytic function in proteins, apart from its inherent practical value, is important for fundamental understanding of enzymatic activity. Using a computationally inexpensive, minimalistic approach that focuses on introducing a single highly reactive residue into proteins to achieve catalysis we converted a 74-residue-long C-terminal domain of calmodulin into an efficient esterase. The catalytic efficiency of the resulting stereoselective, allosterically regulated catalyst, nicknamed AlleyCatE, is higher than that of any previously reported de novo designed esterases. The simplicity of our design protocol should complement and expand the capabilities of current state-of-art approaches to protein design. These results show that even a small nonenzymatic protein can efficiently attain catalytic activities in various reactions (Kemp elimination, ester hydrolysis, retroaldol reaction) as a result of a single mutation. In other words, proteins can be just one mutation away from becoming entry points for subsequent evolution. PMID- 26555771 TI - Motor biases do not influence posing orientation in selfies. AB - When posing for portraits people tend to offer their left cheek. This bias is also evident in selfies: informal photographic self-portraits taken with a smartphone. Mechanical biases have been argued to influence selfie posing orientation (predicting that using the left hand favours a stronger left cheek bias), however this hypothesis has not been directly tested. The present study was thus designed to determine whether motor biases influence selfie pose orientation. Three hundred and twenty participants (F = 159, M = 161) were asked to pose for a selfie "as you really are," and completed a handedness measure; hand used to take the selfie and selfie pose orientation were recorded. Ordinal logistic regression confirmed that neither participant handedness nor hand used to capture the selfie predicted selfie pose orientation. Regardless of sex, handedness, or hand used, participants were more likely to present a midline (49.75%) than a left (26.53%) or right (26.72%) cheek pose. Though handedness was a strong predictor of hand used to capture the selfie (left handers favour the left, and right handers the right, hand), it did not predict posing orientation. These results confirm that selfie cheek biases are not simply a residual effect of the mechanics of taking selfies. PMID- 26555772 TI - Circularly Polarized Luminescence from Helically Chiral N,N,O,O-Boron-Chelated Dipyrromethenes. AB - Helically chiral N,N,O,O-boron chelated dipyrromethenes showed solution-phase circularly polarized luminescence (CPL) in the red region of the visible spectrum (lambdaem (max) from 621 to 663 nm). The parent dipyrromethene is desymmetrised through O chelation of boron by the 3,5-ortho-phenolic substituents, inducing a helical chirality in the fluorophore. The combination of high luminescence dissymmetry factors (|glum | up to 4.7 *10(-3) ) and fluorescence quantum yields (PhiF up to 0.73) gave exceptionally efficient circularly polarized red emission from these simple small organic fluorophores, enabling future application in CPL based bioimaging. PMID- 26555773 TI - Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation. AB - BACKGROUND: Chondrosarcoma is characterized for its lack of response to conventional cytotoxic chemotherapy, propensity for developing lung metastases, and low rates of survival. Research within the field of development and expansion of new treatment options for unresectable or metastatic diseases is of particular priority. Diacerein, a symptomatic slow acting drug in osteoarthritis (SYSADOA), implicates a therapeutic benefit for the treatment of chondrosarcoma by an antitumor activity. METHODS: After treatment with diacerein the growth behaviour of the cells was analyzed with the xCELLigence system and MTS assay. Cell cycle was examined using flow cytometric analysis, RT-PCR, and western blot analysis of specific checkpoint regulators. The status for phosophorylation of mitogen activated protein kinases (MAPKs) was analyzed with a proteome profiler assay. In addition, the possible impact of diacerein on apoptosis was investigated using cleaved caspase 3 and Annexin V/PI flow cytometric analysis. RESULTS: Diacerein decreased the cell viability and the cell proliferation in two different chondrosarcoma cell lines in a dose dependent manner. Flow cytometric analysis showed a classical G2/M arrest. mRNA and protein analysis revealed that diacerein induced a down-regulation of the cyclin B1-CDK1 complex and a reduction in CDK2 expression. Furthermore, diacerein treatment increased the phosphorylation of p38alpha and p38beta MAPKs, and Akt1, Akt2, and Akt 3 in SW-1353, whereas in Cal 78 the opposite effect has been demonstrated. These observations accordingly to our cell cycle flow cytometric analysis and protein expression data may explain the G2/M phase arrest. In addition, no apoptotic induction after diacerein treatment, neither in the Cal-78 nor in the SW-1353 cell line was observed. CONCLUSIONS: Our results demonstrate for the first time that the SYSADOA diacerein decreased the viability of human chondrosarcoma cells and induces G2/M cell cycle arrest by CDK1/cyclin B1 down-regulation. PMID- 26555774 TI - Histochemical changes in neonatal liver caused by vaginal instillation of magnetic nanoparticles in pregnant mice. AB - Drug delivery through the vagina is a novel and effective approach for treating embryonic diseases. Magnetic nanoparticles (MNPs) currently are used as drug delivery systems. The safety of MNPs for use with embryonic tissues remains unclear. We used pregnant mice to investigate the possible toxicity of MNPs toward neonatal liver at three embryonic ages using histochemical and immunohistochemical techniques. MNPs were instilled through the vaginas of pregnant mice at days 12 (E12), 15 (E15) and 17 (E17) after fertilization. We found MNPs in the neonatal liver parenchyma after delivery of the pups on day 20. We observed that MNPs caused mild apoptosis of hepatocytes, cytoplasmic vacuolation and lymphocytic infiltration in the neonatal liver after treatment at E15 compared to instillation at E12 and E17. We observed also that MNPs increased the production of caspase proteins and tumor necrosis factor receptor 2 proteins, which are indicators of apoptosis, in the neonatal liver after instillation of MNPs at E15 compared to instillation at E12 and E17. MNPs also increased the number of collagen fibers and the amounts of connective tissue growth factors in the neonatal liver parenchyma after instillation at E15 compared to instillation at E12 and E17. The general carbohydrates in the neonatal liver were decreased in a time-dependent manner after instillation at E17, E15 and E12 owing to the presence of MNPs in the parenchyma. Overall, we determined that MNPs were mildly toxic to neonatal liver. PMID- 26555775 TI - Correction: Correction: Glucose-Dependent Insulin Secretion in Pancreatic beta Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptorsmographic and Clinico-Epidemiological Features of Dengue Fever in Faisalabad, Pakistan. PMID- 26555776 TI - Associations between the codon 72 polymorphism of the TP53 gene and the risk of recurrent implantation failure. AB - AIM: Recurrent implantation failure (RIF) is the most common cause of unsuccessful pregnancy after assisted reproductive techniques. The tumor protein P53 (TP53) codon 72 polymorphism (G-C transversion) has been explored in susceptibility to RIF, but inconclusive results have been reported. The aim of this article is to estimate the associations between the TP53 codon 72 polymorphism and the risk of RIF. MATERIALS AND METHODS: A comprehensive search for relevant articles was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for CC + GC versus GG, CC versus GC + GG, CC versus GG, GC versus GG genotypes, and C versus G allele, were estimated. Publication bias was explored. Statistical analyses were performed using RevMan 5.2 and Stata 11.0 software. RESULTS: A total of five case-control studies in five articles with 417 RIF cases and 325 controls were included. An overall random effect OR of 1.20 (95% CI, 0.66-2.19; P = 0.55) in the dominant model (CC + GC vs GG) was found. The results suggested that a lack of increased or decreased risks were found in individuals who carried the CC homozygote and heterozygote GC, in comparison with the homozygote GG. However, in subgroup analysis by ethnicity, a significantly increased risk was observed among Latin Americans in the dominant model (OR, 1.56; 95% CI, 1.04-2.33; P = 0.03). CONCLUSIONS: This meta-analysis shows that the TP53 codon 72 polymorphism is not associated with RIF risk in the overall population; however, associations were found in the Latin American population. PMID- 26555778 TI - Versatile Scope of a Masked Aldehyde Nitrone in 1,3-Dipolar Cycloadditions. AB - A new masked aldehyde-containing nitrone 1 that is easily available through a facile one-step procedure has been developed. It undergoes a [3 + 2]-thermal cycloaddition with a wide range of dipolarophiles, affording isoxazolidine cycloadducts that are suitable for versatile postcycloaddition modifications. The acetal cycloadducts are acid-stable, but allow for acetal hydrolysis under mildly basic conditions. The isoxazolidine ring can be opened via an efficient one-pot procedure to give amine-protected gamma-alcohols that can be further converted to furanose derivatives. PMID- 26555777 TI - A puromycin selectable cell line for the enrichment of mouse embryonic stem cell derived V3 interneurons. AB - INTRODUCTION: Spinal V3 interneurons (INs) are a commissural, glutamatergic, propriospinal neuron population that holds great potential for understanding locomotion circuitry and local rewiring after spinal cord injury. Embryonic stem cells hold promise as a cell source. However, the inevitable heterogeneity resulting from differentiation protocols makes studying post-mitotic stem cell derived neuron populations difficult because proliferative glia quickly overtake a culture. Previously, an induction protocol for V3 INs was established. However, because of the heterogeneous population resulting from the induction protocol, functional characterization of the induced cells was not possible. METHODS: A selectable murine transgenic embryonic stem cell (ESC) line (Sim1-Puro) was generated by recombineering. The expression of the puromycin resistance enzyme, puromycin N-acetyl-transferase (PAC), was knocked into the locus of a post mitotic V3 IN marker (Sim1), allowing Sim1 gene regulatory elements to control PAC expression. The resulting cell line was characterized for Sim1 expression by in situ hybridization, for glutamatergic marker expression by immunocytochemistry and quantitative real time polymerase chain reaction (qRT-PCR), and for functional maturation by electrophysiology. RESULTS: Puromycin selection significantly enriched the population for V3 INs, allowing long-term characterization. The selected population expressed the neuronal marker beta-III tubulin and the glutamatergic neuron marker VGluT2. The selected V3 INs also exhibited appropriate functional maturation, as assessed by electrophysiology, and remained glutamatergic for 2 weeks. CONCLUSION: The Sim1-Puro cell line provides a simple, high throughput method for generating large numbers of V3 INs from mouse ESCs for future in vitro and cell transplantation studies. PMID- 26555779 TI - Increasing Discussion Rates of Incontinence in Primary Care: A Randomized Controlled Trial. AB - BACKGROUND: A minority of women with urinary incontinence (UI) and even fewer with fecal incontinence (FI) report having discussed it with a health care provider in the past year. Thus our aim was to evaluate whether the use of an electronic pelvic floor assessment questionnaire (ePAQ-PF) improves communication about incontinence in primary care. METHODS: Women 40 years and older who were scheduled for an annual wellness physical at an internal medicine clinic between August 2007 and August 2008 were randomized to complete the ePAQ-PF prior to (n = 145) or after (n = 139) their visit. Clinicians of women in the intervention group received the ePAQ-PF report prior to the visit. Outcome measures from clinic note abstraction included mention of UI (primary) and FI. Participant reported outcome measures included discussion of UI and FI and initiator of discussion. RESULTS: Discussions of UI was more common in the intervention group than the control group: (27% vs. 19%; odds ratio [OR], 1.6 95% confidence interval [95%CI] 0.9-2.8, particularly for women over 60 (33% vs. 12%; OR 3.8, 95%CI 1.2-11.8) and for women with UI (42% vs. 25%; OR 2.2, 95%CI 1.1-4.1). The intervention primarily led to an increase in clinician-initiated UI discussions which were more common in the intervention group (18% vs. 4%, OR 4.8, 95%CI 1.9 12.0) Participants in the intervention group more frequently reported discussion of FI (14% vs. 6%; OR 2.5, 95%CI 1.1-6.0) which was clinician initiated in over half the cases (9% vs. 3%; OR 3.5, 95%CI 1.1-11.0). CONCLUSIONS: Use of the ePAQ PF prior to clinic visits increases discussion of UI and FI, particularly clinician-initiated discussion. These findings suggest that such instruments may increase the detection and treatment of this often "silent" affliction. PMID- 26555780 TI - Menopause Transition Symptom Clusters: Sleep Disturbances and Sexual Dysfunction. PMID- 26555782 TI - Machine-Learning-Based Prediction of a Missed Scheduled Clinical Appointment by Patients With Diabetes. AB - BACKGROUND: About 10% of patients with diabetes discontinue treatment, resulting in the progression of diabetes-related complications and reduced quality of life. OBJECTIVE: The objective was to predict a missed clinical appointment (MA), which can lead to discontinued treatment for diabetes patients. METHODS: A machine learning algorithm was used to build a logistic regression model for MA predictions, with L2-norm regularization used to avoid over-fitting and 10-fold cross validation used to evaluate prediction performance. Data associated with patient MAs were extracted from electronic medical records and classified into two groups: one related to patients' clinical condition (X1) and the other related to previous findings (X2). The records used were those of the University of Tokyo Hospital, and they included the history of 16 026 clinical appointments scheduled by 879 patients whose initial clinical visit had been made after January 1, 2004, who had diagnostic codes indicating diabetes, and whose HbA1c had been tested within 3 months after their initial visit. Records between April 1, 2011, and June 30, 2014, were inspected for a history of MAs. RESULTS: The best predictor of MAs proved to be X1 + X2 (AUC = 0.958); precision and recall rates were, respectively, 0.757 and 0.659. Among all the appointment data, the day of the week when an appointment was made was most strongly associated with MA predictions (weight = 2.22). CONCLUSIONS: Our findings may provide information to help clinicians make timely interventions to avoid MAs. PMID- 26555783 TI - Cholesterol Oxidation in Fish and Fish Products. AB - Fish and fish products are important from a nutritional point of view due to the presence of high biological value proteins and the high content of polyunsaturated fatty acids, especially those of the n-3 series, and above all eicosapentaenoic acid and docosahexaenoic acid. However, these important food products also contain significant amounts of cholesterol. Although cholesterol participates in essential functions in the human body, it is unstable, especially in the presence of light, oxygen, radiation, and high temperatures that can cause the formation of cholesterol oxidation products or cholesterol oxides, which are prejudicial to human health. Fish processing involves high and low temperatures, as well as other methods for microbiological control, which increases shelf life and consequently added value; however, such processes favor the formation of cholesterol oxidation products. This review brings together data on the formation of cholesterol oxides during the preparation and processing of fish into food products which are recognized and recommended for their nutritional properties. PMID- 26555784 TI - Identification of a Novel Di-D-Fructofuranose 1,2':2,3' Dianhydride (DFA III) Hydrolysis Enzyme from Arthrobacter aurescens SK8.001. AB - Previously, a di-D-fructofuranose 1,2':2,3' dianhydride (DFA III)-producing strain, Arthrobacter aurescens SK8.001, was isolated from soil, and the gene cloning and characterization of the DFA III-forming enzyme was studied. In this study, a DFA III hydrolysis enzyme (DFA IIIase)-encoding gene was obtained from the same strain, and the DFA IIIase gene was cloned and expressed in Escherichia coli. The SDS-PAGE and gel filtration results indicated that the purified enzyme was a homotrimer holoenzyme of 145 kDa composed of subunits of 49 kDa. The enzyme displayed the highest catalytic activity for DFA III at pH 5.5 and 55 degrees C, with specific activity of 232 U mg-1. Km and Vmax for DFA III were 30.7 +/- 4.3 mM and 1.2 +/- 0.1 mM min-1, respectively. Interestingly, DFA III-forming enzymes and DFA IIIases are highly homologous in amino acid sequence. The molecular modeling and docking of DFA IIIase were first studied, using DFA III-forming enzyme from Bacillus sp. snu-7 as a template. It was suggested that A. aurescens DFA IIIase shared a similar three-dimensional structure with the reported DFA III forming enzyme from Bacillus sp. snu-7. Furthermore, their catalytic sites may occupy the same position on the proteins. Based on molecular docking analysis and site-directed mutagenesis, it was shown that D207 and E218 were two potential critical residues for the catalysis of A. aurescens DFA IIIase. PMID- 26555785 TI - Clinical efficacy and safety of topical versus oral ivermectin in treatment of uncomplicated scabies. AB - Many medications are available for scabies treatment including oral and topical ivermectin. However, studies comparing these two forms as a scabies treatment are few. This study compares efficacy and safety of topical versus oral ivermectin as scabies treatment. The study included 62 confirmed uncomplicated scabies patients, divided into: Group I (32 patients, received topical ivermectin) and Group II (30 patients, received oral ivermectin). Patients were assessed, clinically and by KOH smear at 1, 2 and 4 weeks. Treatment was repeated after one week in patients with persistent infection. Adverse events were recorded. Most patients (87.5% and 73.5% in group I and group II respectively) were symptom free after a single treatment. A second treatment was required in 4 patients of group I and 8 patients of group II. However, 2 weeks after treatment symptoms and signs completely resolved in all cases with no recurrence at 4 weeks. This study suggests that both topical and oral ivermectin are safe and equally effective in treatment of uncomplicated scabies. Single treatment, whether topical or oral, is associated with high cure rate in a week post treatment. However, repeating treatment after one week may be required to achieve 100% cure. PMID- 26555786 TI - EFFICACY AND LONG-TERM CLINICAL OUTCOME OF COMORBID POSTTRAUMATIC STRESS DISORDER AND MAJOR DEPRESSIVE DISORDER AFTER ELECTROCONVULSIVE THERAPY. AB - BACKGROUND: Many patients fulfill criteria for both posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Electroconvulsive therapy (ECT) is generally acknowledged to be the most-effective treatment for refractory MDD. This study investigated the efficacy of ECT on long-term clinical outcome of comorbid PTSD and MDD. METHODS: This retrospective nested matched case-control study is inclusive of 22,164 subjects [3,485 with comorbid MDD and PTSD (92 with ECT and 3,393 without ECT) and 18,679 without MDD and PTSD]. RESULTS: Using the clinical global impression scale (CGI) to assess efficacy, more-robust improvement of PTSD and MDD symptoms was observed with ECT (90%), compared to antidepressant-treatment alone(50%) (P = 0.001). During the median of 8 years of follow-up, the death-rate was 8% in subjects without PTSD and MDD, 9.7% in PTSD and MDD treated with ECT and 18% in PTSD and MDD without ECT (P < 0.05). The suicide-rate was 2.2 and 5.9% in PTSD and MDD with and without ECT-treatment, respectively (P < 0.05). Survival-analyses revealed that the relative-risk of cardiovascular and all-cause mortality is not significantly different in patients with comorbid MDD and PTSD treated with ECT, compared to a matched-cohort without PTSD and MDD (P > 0.05). The relative risk of suicidality, all-cause, and cardiovascular mortality was reduced 64, 65, and 46% in MDD and PTSD patients treated with ECT, compared to those without ECT (P < 0.05). CONCLUSION: ECT is associated with a significant reduction of symptoms of PTSD and MDD, as well as reduction in risk of suicidality, cardiovascular, and all-cause mortality in MDD and PTSD, an effect more robust than antidepressant-therapy alone. PMID- 26555787 TI - Alterations in the Colonic Microbiota of Pigs Associated with Feeding Distillers Dried Grains with Solubles. AB - In an effort to reduce feed costs, many pork producers have increased their use of coproducts of biofuel production in commercial pig diets, including increased feeding of distiller's dried grains with solubles (DDGS). The inclusion of DDGS increases the insoluble fiber content in the ration, which has the potential to impact the colonic microbiota considerably as the large intestine contains a dynamic microenvironment with tremendous interplay between microorganisms. Any alteration to the physical or chemical properties of the colonic contents has the potential to impact the resident bacterial population and potentially favor or inhibit the establishment of pathogenic species. In the present study, colonic contents collected at necropsy from pigs fed either 30% or no DDGS were analyzed to examine the relative abundance of bacterial taxa associated with feeding this ingredient. No difference in alpha diversity (richness) was detected between diet groups. However, the beta diversity was significantly different between groups with feeding of DDGS being associated with a decreased Firmicutes:Bacteriodetes ratio (P = .004) and a significantly lower abundance of Lactobacillus spp. (P = .016). Predictive functional profiling of the microbiota revealed more predicted genes associated with carbohydrate metabolism, protein digestion, and degradation of glycans in the microbiota of pigs fed DDGS. Taken together, these findings confirm that alterations in dietary insoluble fiber significantly alter the colonic microbial profile of pigs and suggest the resultant microbiome may predispose to the development of colitis. PMID- 26555790 TI - Copper-Catalyzed Direct C2-Benzylation of Indoles with Alkylarenes. AB - The copper-catalyzed regioselective cross-dehydrogenative coupling of N pyrimidylindoles with benzylic C(sp(3))-H bonds has been developed. Di-tert-butyl peroxide was employed as a mild oxidant, and benzaldehyde proved to be an effective additive. This reaction provides a direct and pratical route to a variety of 2-benzylindoles. PMID- 26555788 TI - Intra-Section Analysis of Human Coronary Arteries Reveals a Potential Role for Micro-Calcifications in Macrophage Recruitment in the Early Stage of Atherosclerosis. AB - BACKGROUND: Vascular calcification is associated with poor cardiovascular outcome. Histochemical analysis of calcification and the expression of proteins involved in mineralization are usually based on whole section analysis, thereby often ignoring regional differences in atherosclerotic lesions. At present, limited information is available about factors involved in the initiation and progression of atherosclerosis. AIM OF THIS STUDY: This study investigates the intra-section association of micro-calcifications with markers for atherosclerosis in randomly chosen section areas of human coronary arteries. Moreover, the possible causal relationship between calcifying vascular smooth muscle cells and inflammation was explored in vitro. TECHNICAL APPROACH: To gain insights into the pathogenesis of atherosclerosis, we performed analysis of the distribution of micro-calcifications using a 3-MeV proton microbeam. Additionally, we performed systematic analyses of 30 to 40 regions of 12 coronary sections obtained from 6 patients including histology and immuno-histochemistry. Section areas were classified according to CD68 positivity. In vitro experiments using human vascular smooth muscle cells (hVSMCs) were performed to evaluate causal relationships between calcification and inflammation. RESULTS: From each section multiple areas were randomly chosen and subsequently analyzed. Depositions of calcium crystals at the micrometer scale were already observed in areas with early pre-atheroma type I lesions. Micro-calcifications were initiated at the elastica interna concomitantly with upregulation of the uncarboxylated form of matrix Gla-protein (ucMGP). Both the amount of calcium crystals and ucMGP staining increased from type I to IV atherosclerotic lesions. Osteochondrogenic markers BMP-2 and osteocalcin were only significantly increased in type IV atheroma lesions, and at this stage correlated with the degree of calcification. From atheroma area type III onwards a considerable number of CD68 positive cells were observed in combination with calcification, suggesting a pro-inflammatory effect of micro-calcifications. In vitro, invasion assays revealed chemoattractant properties of cell-culture medium of calcifying vascular smooth muscle cells towards THP-1 cells, which implies pro-inflammatory effect of calcium deposits. Additionally, calcifying hVSMCs revealed a pro-inflammatory profile as compared to non-calcifying hVSMCs. CONCLUSION: Our data indicate that calcification of VSMCs is one of the earliest events in the genesis of atherosclerosis, which strongly correlates with ucMGP staining. Our findings suggest that loss of calcification inhibitors and/or failure of inhibitory capacity is causative for the early precipitation of calcium, with concomitant increased inflammation followed by osteochondrogenic transdifferentiation of VSMCs. PMID- 26555789 TI - Type 1 Diabetes Prevention in NOD Mice by Targeting DPPIV/CD26 Is Associated with Changes in CD8+T Effector Memory Subset. AB - CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding beta-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to beta pancreatic islets associated to DPPIV inhibitor treatment. PMID- 26555791 TI - Cumulative Doses of T-Cell Depleting Antibody and Cancer Risk after Kidney Transplantation. AB - T-cell depleting antibody is associated with an increased risk of cancer after kidney transplantation, but a dose-dependent relationship has not been established. This study aimed to determine the association between cumulative doses of T-cell depleting antibody and the risk of cancer after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant Registry between 1997-2012, we assessed the risk of incident cancer and cumulative doses of T-cell depleting antibody using adjusted Cox regression models. Of the 503 kidney transplant recipients with 2835 person-years of follow up, 276 (55%), 209 (41%) and 18 (4%) patients received T-cell depleting antibody for induction, rejection or induction and rejection respectively. The overall cancer incidence rate was 1,118 cancers per 100,000 patient-years, with 975, 1093 and 1377 cancers per 100,000 patient-years among those who had received 1-5 doses, 6-10 doses and >10 doses, respectively. There was no association between cumulative doses of T cell depleting antibody and risk of incident cancer (1-5: referent, 6-10: adjusted hazard ratio (HR) 1.19, 95%CI 0.48-2.95, >10: HR 1.42, 95%CI 0.50-4.02, p = 0.801). This lack of association is contradictory to our hypothesis and is likely attributed to the low event rates resulting in insufficient power to detect significant differences. PMID- 26555794 TI - Bioaccumulation of PCBs in liver tissue of dusky Carcharhinus obscurus, sandbar C. plumbeus and white Carcharodon carcharias sharks from south-eastern Australian waters. AB - Polychlorinated biphenyls (PCBs) are ubiquitous pollutants in the marine environment that are known to accumulate in apex predators such as sharks. Liver samples from dusky Carcharhinus obscurus, sandbar Carcharhinus plumbeus, and white Carcharodon carcharias sharks from south-eastern Australian waters were analysed for the seven indicator PCBs 28, 52, 101, 118, 138, 153 and 180. Median ?PCBs were significantly higher in white than sandbar sharks (3.35 and 0.36 MUg g(-1) lipid, respectively, p=0.05) but there were no significant differences between dusky sharks (1.31 MUg g(-1) lipid) and the other two species. Congener concentrations were also significantly higher in white sharks. Significant differences in PCB concentrations between mature and immature dusky (3.78 and 0.76 MUg g(-1) lipid, respectively) and sandbar (1.94 and 0.18 MUg g(-1) lipid, respectively) sharks indicated that PCB concentrations in these species increased with age/growth. Higher-chlorinated congeners (hexa and heptachlorobiphenyls) dominated results, accounting for ~90% of ?PCBs. PMID- 26555792 TI - Two-dimensional slither swimming of sperm within a micrometre of a surface. AB - Sperm motion near surfaces plays a crucial role in fertilization, but the nature of this motion has not been resolved. Using total internal reflection fluorescence microscopy, we selectively imaged motile human and bull sperm located within one micron of a surface, revealing a distinct two-dimensional (2D) 'slither' swimming mode whereby the full cell length (50-80 MUm) is confined within 1 MUm of a surface. This behaviour is distinct from bulk and near-wall swimming modes where the flagellar wave is helical and the head continuously rotates. The slither mode is intermittent (~1 s, ~70 MUm), and in human sperm, is observed only for viscosities over 20 mPa.s. Bull sperm are slower in this surface-confined swimming mode, owing to a decrease in their flagellar wave amplitude. In contrast, human sperm are ~50% faster-suggesting a strategy that is well suited to the highly viscous and confined lumen within the human fallopian tube. PMID- 26555795 TI - Quality Index of Subtidal Macroalgae (QISubMac): A suitable tool for ecological quality status assessment under the scope of the European Water Framework Directive. AB - Despite their representativeness and importance in coastal waters, subtidal rocky bottom habitats have been under-studied. This has resulted in a lack of available indicators for subtidal hard substrate communities. However, a few indicators using subtidal macroalgae have been developed in recent years for the purpose of being implemented into the Water Framework Directive (WFD). Accordingly, a quality index of subtidal macroalgae has been defined as a French assessment tool for subtidal rocky bottom habitats in coastal waters. This approach is based on 14 metrics that consider the depth penetration, composition (sensitive, characteristic and opportunistic) and biodiversity of macroalgae assemblages and complies with WFD requirements. Three ecoregions have been defined to fit with the geographical distribution of macroalgae along the French coastline. As a test, QISubMac was used to assess the water quality of 20 water bodies. The results show that QISubMac may discriminate among different quality classes of water bodies. PMID- 26555796 TI - Polycyclic aromatic hydrocarbons alter the structure of oceanic and oligotrophic microbial food webs. AB - One way organic pollutants reach remote oceanic regions is by atmospheric transport. During the Malaspina-2010 expedition, across the Atlantic, Indian, and Pacific Oceans, we analyzed the polycyclic aromatic hydrocarbon (PAH) effects on oceanic microbial food webs. We performed perturbation experiments adding PAHs to classic dilution experiments. The phytoplankton growth rates were reduced by more than 5 times, being Prochlorococcus spp. the most affected. 62% of the experiments showed a reduction in the grazing rates due to the presence of PAHs. For the remaining experiments, grazing usually increased likely due to cascading effects. We identified changes in the slope of the relation between the growth rate and the dilution fraction induced by the pollutants, moving from no grazing to V-shape, or to negative slope, indicative of grazing increase by cascade effects and alterations of the grazers' activity structure. Our perturbation experiments indicate that PAHs could influence the structure oceanic food-webs structure. PMID- 26555797 TI - Distribution, sources, and fluxes of heavy metals in the Pearl River Delta, South China. AB - Riverine samples were collected at various locations in the Pearl River Delta (PRD) to determine the concentrations of heavy metals (Cr, Ni, Cu, Mn, Zn, Cd, and Pb) in time and space and to estimate the fluxes of heavy metals to the coastal waters off South China. Most of the elements exhibit clear temporal and spatial trends. Principal component analysis shows that surface erosion is the major factor affecting metal concentrations in particulates in the PRD. Natural geology is an important source of these heavy metals. The annual fluxes of Cr, Ni, Cu, Mn, Zn, Cd, and Pb in upstream and downstream were 445, 256, 241, 3293, 1279, 12, and 317 t/year and 1823, 1144, 1786, 15,634, 6183, 74, and 2017 t/year, respectively. A comparison indicated that the annual fluxes of Mn accounted for 1.3% of the global river fluxes, whereas other elements contribute <1%. PMID- 26555798 TI - Ventromedial hypothalamic lesions downregulate multiple immune signaling pathways in rat pancreatic islets. AB - It was recently reported that ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and metabolism-related genes in rat pancreatic islets. This study has examined how gene families involved in immune responses are regulated in rat pancreatic islets after VMH lesions formation. Total pancreatic islets RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions downregulated multiple immune signaling pathways in rat pancreatic islets. Real-time polymerase chain reaction also confirmed that gene expressions of RT1 class II, locus Bb (RT1-Bb) was up-regulated and Spi-B transcription factor (Spib) was downregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of multiple immune response genes in rat pancreatic islets. PMID- 26555799 TI - Sextant-Specific Analysis of Detection and Tumor Volume by HistoScanningTM. AB - INTRODUCTION: Published results of HistoScanningTM (HS) for prostate cancer (PCa) diagnostics are inconsistent and their value remains unclear. We prospectively analyzed the detection rate and tumor volume concordance in PCa patients. MATERIAL AND METHODS: Two hundred and eighty-two patients with biopsy-proven PCa scheduled for radical prostatectomy (RP) were included. All patients underwent ultrasonographical examination by HS prior to surgery. HS was evaluated compared to RP specimen as to (1) the prediction of overall tumor volume and (2) accuracy of HS in detection of PCa lesions larger than 0.2/0.5 ml, separated for each sextant. For each sextant, receiver operating characteristic (ROC)-analysis and area under the curve were determined. Sensitivity and specificity were calculated and visualized in ROC-curves. RESULTS: HS tends to underestimate volume of cancerous lesions, particularly larger lesions >8 ml. Using a 0.2 ml detection threshold, specificity and sensitivity of HS were between 29-68% and 46-78%. For a 0.5 ml detection threshold, sextant-specific specificity increased to 59-92% and sensitivity decreased to 16-54%. Stratification according to pre-operational PSA values did not improve performance characteristics of HS. CONCLUSIONS: Our results do not support a significant contribution of HS to PCa diagnostics. PMID- 26555800 TI - Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function. AB - In vitro models of thrombocytopenia are useful research tools. Previously published models have shortcomings altering properties of platelets and other blood components. The aim of the present study was to develop a whole blood method to induce thrombocytopenia with minimal manipulation, and to describe platelet function in induced thrombocytopenia in individuals with healthy platelets. Hirudin anticoagulated blood was obtained from 20 healthy volunteers. One part of the blood was gently centrifuged at 130g for 15 minutes. The platelet rich plasma was replaced with phosphate-buffered saline to establish thrombocytopenia. Various levels of thrombocytopenia were achieved by combining different volumes of baseline whole blood and thrombocytopenic blood. Platelet counts were measured by flow cytometry (Navios, Beckman Coulter) and routine haematological analyser (Sysmex XE-5000). Platelet function was analysed by impedance aggregometry (Multiplate(r) Analyzer, Roche) and by flow cytometry (Navios, Beckman Coulter) using collagen, adenosine diphosphate, thrombin receptor activating peptide-6 and ristocetin as agonists. Median baseline platelet count was 227*10(9)/l. The in vitro model yielded median platelet counts at 51*10(9)/l (range 26-93*10(9)/l). We observed minor, yet significant, changes in platelet size and maturity from baseline to modelled thrombocytopenia. In the thrombocytopenic samples, significant and positive linear associations were found between platelet count and platelet aggregation across all agonists (all p values<0.001). Platelet function assessed by flow cytometry showed minimal alterations in the thrombocytopenic samples. A new whole blood-based model of thrombocytopenia was established and validated. This new model serves as a useful future tool, particularly to explore platelet function in patients with thrombocytopenia. PMID- 26555801 TI - Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma. AB - Apoptosis plays an important role in the treatment of cancer, and targeting apoptosis-related molecules in ovarian cancer (OC) is of great therapeutic value. Melatonin (Mel) is an indoleamine displaying several anti-cancer properties and has been reported to modulate apoptosis signaling in multiple tumor subtypes. We investigated OC and the role of Mel therapy on the pro-apoptotic (p53, BAX, caspase-3, and cleaved caspase-3) and anti-apoptotic (Bcl-2 and survivin) proteins in an ethanol (EtOH)-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 MUg 7,12 dimethylbenz(a)anthracene dissolved in 10 MUl of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 MUg/100 g BW per day) for 60 days. Body weight gain, EtOH consumption, and energy intake were unaffected by the treatments. Interestingly, absolute and relative OC masses showed a significant reduction after Mel therapy, regardless of EtOH consumption. To accomplish OC-related apoptosis, we first observed that p53, BAX, caspase-3, and cleaved caspase-3 were downregulated in OC tissue while Bcl-2 and survivin were overexpressed. Notably, Mel therapy and EtOH intake promoted apoptosis along with the upregulation of p53, BAX, and cleaved caspase-3. Fragmentation of DNA observed by TUNEL-positive nuclei was also enhanced following Mel treatment. In addition, Bcl-2 was downregulated by the EtOH intake and lower survivin levels were observed after Mel therapy. Taken together, these results suggest that Mel induce apoptosis in OC cells of EtOH-preferring animals. PMID- 26555802 TI - Development of Sulfidogenic Sludge from Marine Sediments and Trichloroethylene Reduction in an Upflow Anaerobic Sludge Blanket Reactor. AB - The importance of microbial sulfate reduction relies on the various applications that it offers in environmental biotechnology. Engineered sulfate reduction is used in industrial wastewater treatment to remove large concentrations of sulfate along with the chemical oxygen demand (COD) and heavy metals. The most common approach to the process is with anaerobic bioreactors in which sulfidogenic sludge is obtained through adaptation of predominantly methanogenic granular sludge to sulfidogenesis. This process may take a long time and does not always eliminate the competition for substrate due to the presence of methanogens in the sludge. In this work, we propose a novel approach to obtain sulfidogenic sludge in which hydrothermal vents sediments are the original source of microorganisms. The microbial community developed in the presence of sulfate and volatile fatty acids is wide enough to sustain sulfate reduction over a long period of time without exhibiting inhibition due to sulfide. This protocol describes the procedure to generate the sludge from the sediments in an upflow anaerobic sludge blanket (UASB) type of reactor. Furthermore, the protocol presents the procedure to demonstrate the capability of the sludge to remove by reductive dechlorination a model of a highly toxic organic pollutant such as trichloroethylene (TCE). The protocol is divided in three stages: (1) the formation of the sludge and the determination of its sulfate reducing activity in the UASB, (2) the experiment to remove the TCE by the sludge, and (3) the identification of microorganisms in the sludge after the TCE reduction. Although in this case the sediments were taken from a site located in Mexico, the generation of a sulfidogenic sludge by using this procedure may work if a different source of sediments is taken since marine sediments are a natural pool of microorganisms that may be enriched in sulfate reducing bacteria. PMID- 26555803 TI - Sustained-release of Cyclosporin A pellets: preparation, in vitro release, pharmacokinetic studies and in vitro-in vivo correlation in beagle dogs. AB - The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro-in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18 +/- 0.17 g/100 g), good stability and showed a sustained-release effect. The Cmax, Tmax and AUC0-24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22 +/- 15.99 ng/ml, 6 +/- 0 h and 3205.00 +/- 149.55 ng.h/ml, respectively. Compared with Neoral(r), CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24 h. The relative bioavailability of CsA pellets was 125.68 +/- 5.37% that of Neoral(r). Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24 h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC. PMID- 26555804 TI - Structural Degradation and Swelling of Lipid Bilayer under the Action of Benzene. AB - Benzene and other nonpolar organic solvents can accumulate in the lipid bilayer of cellular membranes. Their effect on the membrane structure and fluidity determines their toxic properties and antibiotic action of the organic solvents on the bacteria. We performed molecular dynamics simulations of the interaction of benzene with the dimyristoylphosphatidylcholine (DMPC) bilayer. An increase in the membrane surface area and fluidity was clearly detected. Changes in the acyl chain ordering, tilt angle, and overall bilayer thickness were, however, much less marked. The dependence of all computed quantities on the benzene content showed two regimes separated by the solubility limit of benzene in water. When the amount of benzene exceeded this point, a layer of almost pure benzene started to grow between the membrane leaflets. This process corresponds to the nucleation of a new phase and provides a molecular mechanism for the mechanical rupture of the bilayer under the action of nonpolar compounds. PMID- 26555805 TI - Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology. AB - Multienzyme polyketide synthases (PKSs) are molecular-scale assembly lines which construct complex natural products in bacteria. The underlying modular architecture of these gigantic catalysts inspired, from the moment of their discovery, attempts to modify them by genetic engineering to produce analogues of predictable structure. These efforts have resulted in hundreds of metabolites new to nature, as detailed in this review. However, in the face of many failures, the heady days of imagining the possibilities for a truly 'combinatorial biosynthesis' of polyketides have faded. It is now more appropriate to talk about 'PKS synthetic biology' with its more modest goals of delivering specific derivatives of known structure in combination with and as a complement to synthetic chemistry approaches. The reasons for these failures will be discussed in terms of our growing understanding of the three-dimensional architectures and mechanisms of these systems. Finally, some thoughts on the future of the field will be presented. PMID- 26555807 TI - An amyloid-like cascade hypothesis for C9orf72 ALS/FTD. AB - Expansion of a GGGGCC repeat in C9orf72 causes amyotrophic lateral sclerosis, frontotemporal dementia, or a combination of both. Bidirectional repeat transcripts sequester RNA-binding proteins into nuclear RNA foci. The repeat is translated into dipeptide repeat (DPR) proteins that are crucial for repeat induced toxicity. DPRs inhibit the proteasome and sequester other proteins. These changes are accompanied by widespread brain atrophy and subclinical cognitive impairment before disease onset. Both repeat RNA and DPRs impair nucleocytoplasmic transport and promote TDP-43 mislocalization and aggregation. Thus, repeat RNA and DPRs may gradually trigger TDP-43 pathology and subsequent region-specific neurodegeneration in a cascade similar to amyloid-beta peptide in Alzheimer's disease. The key components of the C9orf72 cascade are promising therapeutic targets in different disease stages. PMID- 26555806 TI - New statistical approaches exploit the polygenic architecture of schizophrenia- implications for the underlying neurobiology. AB - Schizophrenia is a complex disorder with high heritability. Recent findings from several large genetic studies suggest a large number of risk variants are involved (i.e. schizophrenia is a polygenic disorder) and analytic approaches could be tailored for this scenario. Novel statistical approaches for analyzing GWAS data have recently been developed to be more sensitive to polygenic traits. These approaches have provided intriguing new insights into neurobiological pathways and support for the involvement of regulatory mechanisms, neurotransmission (glutamate, dopamine, GABA), and immune and neurodevelopmental pathways. Integrating the emerging statistical genetics evidence with sound neurobiological experiments will be a crucial, and challenging, next step in deciphering the specific disease mechanisms of schizophrenia. PMID- 26555808 TI - RSV infections: State of the art. AB - Respiratory syncytial virus (RSV) is one of the most common lower respiratory disease in infants and young children worldwide. Despite its long history, a safe and effective cure for RSV remains elusive. Nonetheless, further understanding of RSV pathogenesis and risk factors have led to advances in prophylaxis and management. The leading risk factor for RSV is premature birth, primarily because fewer protective antibodies are transmitted from the mother to the infant. For full-term born infants, susceptibility to RSV increases as maternal IgG titers decline to a nadir at 2 to 3 months of age. Because of the unique pathophysiologic mechanisms involved in this infection, it is likely that future treatment strategies will focus on modulating the host immune response to the virus, rather than virucidal or virustatic molecules. PMID- 26555809 TI - Dermatology for the pediatrician: Advances in diagnosis and treatment of common and not-so-common skin conditions. AB - Advances have been made in understanding and treating both common and rare dermatologic conditions. Atopic dermatitis benefits from bathing and ceramide moisturizers. Common allergic contact dermatitis may have specific presentations. Tinea capitis is effectively treated with terbinafine. Infantile hemangiomas should be treated early in the disease course and respond well to propranolol; any white sign of ulceration should be noted. Localized alopecia areata responds well to topical clobetasol, avoiding the need for intralesional injections. Topical rapamycin can be used to treat tuberous sclerosis. Further understanding of genetics will help guide pediatricians to the proper diagnosis and treatment of skin conditions. PMID- 26555810 TI - ADHD and behavioral disorders: Assessment, management, and an update from DSM-5. AB - Behavioral disorders in pediatric patients--primarily attention deficit hyperactivity disorder (ADHD)--pose a clinical challenge for health care providers to accurately assess, diagnose, and treat. In 2013, updated diagnostic criteria for behavioral disorders were published, including ADHD and a new diagnostic entity: disruptive mood dysregulation disorder. Revised criteria for ADHD includes oldest age for occurrence of symptoms, need for symptoms to be present in more than one setting, and requirement for number of symptoms in those aged 17 and older. Assessment of ADHD relies primarily on the clinical interview, including the medical and social history, along with the aid of objective measures. The clinical course of ADHD is chronic with symptom onset occurring well before adolescence. Most patients have symptoms that continue into adolescence, and some into adulthood. Many patients with ADHD have comorbid disorders such as depression, disruptive behavior disorders, or substance abuse, which need to be addressed first in the treatment plan. Treatment of ADHD relies on a combination of psychopharmacologic, academic, and behavioral interventions, which produce response rates up to 80%. PMID- 26555811 TI - Learning disorders: How pediatricians can help. AB - Learning disabilities are common and can negatively affect the individual and, ultimately, society. Pediatricians should be able to identify the risk factors for learning disabilities, recognize the early warning signs, and apply the appropriate diagnostic tools. Pediatricians also can play a crucial role by encouraging schools to provide accommodations for the child, requesting multifactorial evaluations from the school district, and referring patients for detailed neuropsychological evaluation outside the school district when appropriate. Information from the pediatrician can help the school formulate an individualized education plan for the child. Additionally, the primary care pediatrician can support families with referrals to appropriate healthcare specialists. PMID- 26555812 TI - Developmental delays and autism: Screening and surveillance. AB - Screening and surveillance are crucial components to the early detection of developmental disorders in children, which enables early interventions that provide the best chances for improved outcomes. Identifying a developmental disorder is the initial step in evaluating the disorder. Surveillance is a flexible, continuous, longitudinal process aimed at identifying concerns, and it should be performed at every well-child visit. Screening involves administering a brief, standardized tool normalized for specific ages and stages of development to identify any developmental delays or specific concerns such as autism. Screening is recommended at every office visit and whenever a parent expresses a concern. Two general types of screening tests are available: problem-specific screening and broadband developmental screening. For each type, there are multiple different tests available that can be administered by a parent or a health care provider. Factors to consider in the test selection are the age range for which it is intended, time it takes to complete and score, cost, whether the test is paper-based or electronic, and the language availability. PMID- 26555813 TI - Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy. AB - Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs. PMID- 26555814 TI - Cytotoxic T Lymphocyte Antigen-4 Down-Regulates T Helper 1 Cells by Increasing Expression of Signal Transducer and Activator of Transcription 3 in Acute Graft versus-Host Disease. AB - Numerous previous studies have suggested that cytotoxic T lymphocyte antigen-4 (CTLA-4) plays an important role in acute graft-versus-host disease (GVHD). How CTLA-4 acts in regulating acute GVHD remains unknown, however. In the present study, we found that, compared with healthy controls, CTLA-4 plasma and relative mRNA levels in patients with acute GVHD were initially decreased and then markedly elevated after 28 days of treatment. CTLA-4 levels were higher in patients with grade I-II acute GVHD compared with those with grade III-IV acute GVHD both before and after treatment. Up-regulation of CTLA-4 significantly increased the luciferase activity and degree of phosphorylation of signal transducer and activator of transcription 3 (STAT3). Meanwhile, T cell activation was significantly inhibited, and levels of IFN-gamma, IL-17, and IL-22 decreased. These findings suggest that CTLA-4 might be involved in the pathogenesis of acute GVHD, and may down-regulate T helper 1 cells by increasing STAT3 expression in acute GVHD. PMID- 26555815 TI - Novel Application of Laparoscopic Ultrasound for Fetoscopic Laser Ablation in Twin-Twin Transfusion Syndrome with Complete Anterior Placenta. AB - Fetoscopic laser coagulation of the placental communicating vessels has become the standard treatment for monochorionic/diamniotic twin pregnancies complicated by severe twin-twin transfusion syndrome. Fetoscopic trocar placement can be performed with transabdominal ultrasound guidance with a posterior placenta and most anterior placentas that have a safe avascular window for entry. However, trocar insertion is challenging in cases of a complete anterior placenta without an avascular window. Current techniques to deal with this situation include mini laparotomy with exteriorization to allow for dorsal entry, percutaneous lateral entry under transabdominal ultrasound/Doppler guidance, and laparoscopic assisted access with direct visualization of trocar entry. We describe a modified technique of laparoscopic assisted fetoscopic trocar placement using a laparoscopic ultrasound probe, which allows for precise, real-time guidance of trocar placement. PMID- 26555816 TI - Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult. AB - The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID- 26555817 TI - Conditional Knockout of Telomerase Reverse Transcriptase in Mesenchymal Cells Impairs Mouse Pulmonary Fibrosis. AB - Telomerase is typically expressed in cellular populations capable of extended replication, such as germ cells, tumor cells, and stem cells, but is also induced in tissue injury, repair and fibrosis. Its catalytic component, telomerase reverse transcriptase (TERT) is induced in lung fibroblasts from patients with fibrotic interstitial lung disease and in rodents with bleomycin-induced pulmonary fibrosis. To evaluate the fibroblast specific role of TERT in pulmonary fibrosis, transgenic mice bearing a floxed TERT allele were generated, and then crossed with an inducible collagen alpha2(I)-Cre mouse line to generate fibroblast specific TERT conditional knockout mice. TERT-specific deficiency in mesenchymal cells caused attenuation of pulmonary fibrosis as manifested by reduced lung hydroxyproline content, type I collagen and alpha-smooth muscle actin mRNA levels. The TERT-deficient mouse lung fibroblasts displayed decreased cell proliferative capacity and higher susceptibility to induced apoptosis compared with control cells. Additionally TERT deficiency was associated with heightened alpha-smooth muscle actin expression indicative of myofibroblast differentiation. However the impairment of cell proliferation and increased susceptibility to apoptosis would cause a reduction in the myofibroblast progenitor population necessary to mount a successful myofibroblast-dependent fibrotic response. These findings identified a key role for TERT in fibroblast proliferation and survival essential for pulmonary fibrosis. PMID- 26555818 TI - Physiological Response of the Hard Coral Pocillopora verrucosa from Lombok, Indonesia, to Two Common Pollutants in Combination with High Temperature. AB - Knowledge on interactive effects of global (e.g. ocean warming) and local stressors (e.g. pollution) is needed to develop appropriate management strategies for coral reefs. Surfactants and diesel are common coastal pollutants, but knowledge of their effects on hard corals as key reef ecosystem engineers is scarce. This study thus investigated the physiological reaction of Pocillopora verrucosa from Lombok, Indonesia, to exposure with a) the water-soluble fraction of diesel (determined by total polycyclic aromatic hydrocarbons (PAH); 0.69 +/- 0.14 mg L-1), b) the surfactant linear alkylbenzene sulfonate (LAS; 0.95 +/- 0.02 mg L-1) and c) combinations of each pollutant with high temperature (+3 degrees C). To determine effects on metabolism, respiration, photosynthetic efficiency and coral tissue health were measured. Findings revealed no significant effects of diesel, while LAS resulted in severe coral tissue losses (16-95% after 84 h). High temperature led to an increase in photosynthetic yield of corals after 48 h compared to the control treatment, but no difference was detected thereafter. In combination, diesel and high temperature significantly increased coral dark respiration, whereas LAS and high temperature caused higher tissue losses (81 100% after 84 h) and indicated a severe decline in maximum quantum yield. These results confirm the hypothesized combined effects of high temperature with either of the two investigated pollutants. Our study demonstrates the importance of reducing import of these pollutants in coastal areas in future adaptive reef management, particularly in the context of ocean warming. PMID- 26555819 TI - Diminution of Oxidative Damage to Human Erythrocytes and Lymphocytes by Creatine: Possible Role of Creatine in Blood. AB - Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their lifespan. PMID- 26555820 TI - sigma54-dependent regulome in Desulfovibrio vulgaris Hildenborough. AB - BACKGROUND: The sigma(54) subunit controls a unique class of promoters in bacteria. Such promoters, without exception, require enhancer binding proteins (EBPs) for transcription initiation. Desulfovibrio vulgaris Hildenborough, a model bacterium for sulfate reduction studies, has a high number of EBPs, more than most sequenced bacteria. The cellular processes regulated by many of these EBPs remain unknown. RESULTS: To characterize the sigma(54)-dependent regulome of D. vulgaris Hildenborough, we identified EBP binding motifs and regulated genes by a combination of computational and experimental techniques. These predictions were supported by our reconstruction of sigma(54)-dependent promoters by comparative genomics. We reassessed and refined the results of earlier studies on regulation in D. vulgaris Hildenborough and consolidated them with our new findings. It allowed us to reconstruct the sigma(54) regulome in D. vulgaris Hildenborough. This regulome includes 36 regulons that consist of 201 coding genes and 4 non-coding RNAs, and is involved in nitrogen, carbon and energy metabolism, regulation, transmembrane transport and various extracellular functions. To the best of our knowledge, this is the first report of direct regulation of alanine dehydrogenase, pyruvate metabolism genes and type III secretion system by sigma(54)-dependent regulators. CONCLUSIONS: The sigma(54) dependent regulome is an important component of transcriptional regulatory network in D. vulgaris Hildenborough and related free-living Deltaproteobacteria. Our study provides a representative collection of sigma(54)-dependent regulons that can be used for regulation prediction in Deltaproteobacteria and other taxa. PMID- 26555821 TI - Knowledge and attitude of pregnant women toward flu vaccination: a cross sectional survey. AB - OBJECTIVE: The study was conducted to explore the knowledge of pregnant women about influenza, influenza vaccine during pregnancy and the attitudes regarding immunization. METHODS: A questionnaire based on the model proposed by Yudin in 2009 was translated, adapted and administered to 309 pregnant women in the third trimester of pregnancy between October 1 and December 1, 2013 at San Giovanni Calibita Fatebenefratelli hospital of Rome (Italy). RESULTS: Most of the interviewed women (68.9%) answered that influenza is highly contagious, 34.6% of them believed that pregnant women have the same risk of complications as non pregnant women. Only 5.8% were aware that the vaccine is recommended for women in the second and third trimester of pregnancy and only 14.2% of women answered that the vaccine is safe during pregnancy. Only 3/309 women reported recommendation and offer of vaccination during current pregnancy, but none of them was vaccinated. CONCLUSIONS: Overall, knowledge regarding influenza, implications during pregnancy and influenza vaccine was poor among pregnant women. In Italy, the National Vaccine Prevention Plan 2012-2014 recommends influenza vaccine during pregnancy, but only 18/309 were aware of this recommendation. These results suggest that in order to increase influenza vaccine acceptance it is necessary to improve pregnant women knowledge about influenza and to offer education to healthcare providers. PMID- 26555822 TI - Natural occurrence of bisphenol F in mustard. AB - Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg( 1). Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4'-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of Sinapis alba contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (Brassica juncea) or black mustard seeds (Brassica nigra) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100-200 ug of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols. PMID- 26555823 TI - Red-Light-Induced Decomposition of an Organic Peroxy Radical: A New Source of the HO2 Radical. AB - The gas-phase decomposition of the alpha-hydroxy methylperoxy radical has been theoretically examined, and the results provide insight into a new source of the hydroperoxy radical (HO2 ) in the troposphere. Bimolecular peroxy decomposition is promoted by the red-light or near-IR radiation excitation. The calculations suggest for the first time, an important chemical role for the H2 O?HO2 radical complex that exist in significant abundance in the troposphere. In particular, the reaction of organic peroxy radicals with the HO2 radical and the H2 O?HO2 radical complex represent an autocatalytic source of atmospheric HO2 . This reaction is a new example of red-light-initiated atmospheric chemistry that may help in understanding the discrepancy between the observed and measured levels of the HOx at sunrise. PMID- 26555824 TI - Toward the Development of a Universal Outcome Instrument for Spine Trauma: A Systematic Review and Content Comparison of Outcome Measures Used in Spine Trauma Research Using the ICF as Reference. AB - STUDY DESIGN: A systematic literature review. OBJECTIVE: The aim of this study was (1) to identify patient-reported and clinician-based outcome measures most frequently used to evaluate the function and health of spine trauma patients, (2) to identify and quantify the concepts of these measures using the International Classification of Functioning, Disability, and Health (ICF) as reference, and (3) to describe their clinimetric properties. SUMMARY OF BACKGROUND DATA: There is a real need for a disease-specific outcome instrument to measure the effect size of various treatment options in a variety of traumatic spinal column injuries. METHODS: A systematic literature search was conducted in several databases. From the included studies, outcome measures were extracted. The items and underlying concepts of the identified outcome measures were specified and linked to the ICF categories. Finally, as far as available in literature, the clinimetric properties of the obtained measures were analyzed. RESULTS: Out of 5117 screened references, 245 were included, and 17 different frequently used outcome measures were identified. Meaningful concepts of the items and response options of the retrieved outcome measures were linked to a total of 105 different ICF categories, aggregated to 57 first- or second-level categories. The categories were linked to the components activities and participation (n = 31), body functions (n = 17), environmental factors (n = 8), and body structures (n = 1). Overall, there is only limited evidence on the measurement properties, except for some disease-specific questionnaires, such as Oswestry Disability Index, Roland Morris Disability Questionnaire, Neck Disability Index, and Cervical Spine Outcome Questionnaire. CONCLUSION: The current systematic literature review revealed great diversity in the use and content of outcome measures to evaluate the functioning and health of spine trauma patients, with 17 different outcome measures linked to 57 unique ICF categories. This study creates an evidence base for a consensus meeting during which a core set of ICF categories for outcome measurement in spine trauma will be decided. LEVEL OF EVIDENCE: 2. PMID- 26555825 TI - The Triangle Model of Congenital Cervical Stenosis. AB - STUDY DESIGN: Retrospective Cross-Sectional Study OBJECTIVE.: Identify the pathoanatomical features of the cervical spine associated with congenital stenosis SUMMARY OF BACKGROUND DATA.: Congenital cervical stenosis (CCS) describes a patient with a decreased spinal canal diameter at multiple levels of the cervical spine in the absence of degenerative changes. Despite recognition of CCS throughout the literature, the anatomical features that lead to this condition have not been established. Knowledge of the pathoanatomy behind CCS may lead to alterations in surgical technique for this patient population that may improve outcomes. METHODS: From 1000 cervical MRIs between January 2000 and December 2014, CCS was identified in 68 patients using a strict definition of age less than 50 years with mid-sagittal canal diameters (mid-SCD) (<10 mm) at multiple sub-axial cervical levels (C3-C7). A total of 68 patients met the inclusion criteria for this group. Fourteen controls with normal SCDs (>14 mm) at all cervical levels were used for comparison. Anatomic measurements obtained at each level (C3-C7) included: coronal vertebral body, AP vertebral body, pedicle width, pedicle length, laminar length, AP lateral mass, posterior canal distance, lamina-pedicle angle, and lamina-disc angle (LDA). Statistical significance was defined as P < 0.01. RESULTS: CCS patients demonstrated significantly different anatomical measurements when compared with controls. Significantly smaller lateral masses, lamina lengths, lamina-pedicle angles, and larger LDAs were identified at levels C3 to C7 in the CCS group (P < 0.01). These anatomic components form a right triangle that illustrates the cumulative narrowing effect on space for the spinal cord. CONCLUSION: The pathoanatomy of CCS is associated with a decrease in the lamina-pedicle angle and an increase in the LDA ultimately leading to a smaller SCD. The global changes in CCS are best illustrated by this triangle model and are driven by the posterior elements of the cervical spine. LEVEL OF EVIDENCE: 4. PMID- 26555826 TI - A Survey of Innovative Reimbursement Models in Spine Care. AB - STUDY DESIGN: Structured key informant interviews with follow-up. OBJECTIVE: The aim of the study was to describe innovative reimbursement models in spine care and gather perspectives on the future of spine care reimbursement. SUMMARY OF BACKGROUND DATA: The United States spends $90 billion annually on medical expenses for low back pain. One approach to promoting high-quality, cost effective care is through bundled payments and other reimbursement models wherein physicians are held accountable for costs and utilization. Little data exist on innovative payment models in spine care. METHODS: Through literature review and discussions with leaders in the field, we identified organizations that were engaged in bundled payment initiatives for spine care and surgery. These included healthcare systems, physician groups, organizations helping to set up bundles, and a large employer. We conducted interviews to understand the background and specific features of each initiative, generalizable success factors and challenges, and perspectives on the future of spine reimbursement. RESULTS: We interviewed 24 stakeholders across 18 organizations that collectively perform approximately 12,000 inpatient spine surgeries annually. Fee-for-service reimbursement accounts for a majority of revenue, but several organizations expect 30% to 45% of their spine volume to be covered under bundled payments within 3 years and cite new patient volume, increased surgical yield, and financial benefits from efficiency improvements as reasons for adopting bundled payments. Current initiatives are heterogeneous, but share similar success factors and challenges. Institutions are more hesitant to adopt risk-based payment models for chronic back care, citing difficulty modeling risk, patient heterogeneity, and difficulty aligning incentives. CONCLUSION: Payment models outside of the traditional fee-for-service paradigm are emerging in spine care. Providers that preemptively adopt bundled payments can increase patient volumes from payers seeking cost-effective care. Going forward, organizations should begin considering reimbursement models that focus on noninterventional spine care. Finally, developments in spine reimbursement may apply to other procedure based specialties, including orthopedics and cardiology. LEVEL OF EVIDENCE: 5. PMID- 26555827 TI - Body Image and Quality-of-Life in Untreated Versus Brace-Treated Females With Adolescent Idiopathic Scoliosis. AB - STUDY DESIGN: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) included skeletally immature high-risk patients with adolescent idiopathic scoliosis (AIS) with moderate curve sizes (20 degrees - 40 degrees ). BrAIST was a multicenter, controlled trial using both randomized and preference treatment arms into either an observation group or a brace treatment group. OBJECTIVE: The aim of this study was to analyze and compare body image and quality-of-life (QOL) in female AIS patients who were observed or treated with a brace. SUMMARY OF BACKGROUND DATA: Brace treatment is an effective means for controlling progressive scoliosis and preventing the need for surgery, but there is no consensus regarding the effect of brace treatment on body image or on QOL in adolescents with AIS. METHODS: Data from female BrAIST patients in the randomized (n = 132) or preference (n = 187) arms and were observed (n = 120) or brace treated (n = 199) were analyzed. Patients completed the Spinal Appearance Questionnaire (SAQ) and the Pediatric Quality of Life Inventory (PedsQOL) 4.0 Generic Scales at baseline and 6 month follow-up visits up to 2 years. Items on the SAQ measured three body image constructs (self, ideal, and overall). The PedsQOL measured health, activities, feelings, social factors, and school. RESULTS: . In general, there were no significant differences within or between study arms or treatments regarding body image or QOL through 2 years of follow up. Poorer body image was significantly correlated with poorer QOL during the first 2 years of follow-up regardless of study arm or treatment. Patients who crossed-over to a different treatment and patients with largest Cobb angles >= 40 degrees had significantly poorer body image, in particular self-body image, compared with those that did not. CONCLUSION: This study does not support findings from previous research indicating that wearing a brace has a negative impact on or is negatively impacted by body image or QOL. LEVEL OF EVIDENCE: 2. PMID- 26555828 TI - Risk Factors for Recurrence of Surgically Treated Conventional Spinal Schwannomas: Analysis of 169 Patients From a Multicenter International Database. AB - STUDY DESIGN: A retrospective analysis of 169 adult patients operated for a conventional spinal schwannoma from the AOSpine Multicenter Primary Spinal Tumors Database. OBJECTIVE: The aim of this study is to identify risk factors for local recurrence of conventional spinal schwannoma in patients who had surgery. SUMMARY OF BACKGROUND DATA: Schwannomas account for up to 30% of all adult spinal tumors. Total resection is the gold standard for patients with sensory or motor deficits. Local recurrence is reported to be approximately 5% and usually occurs several years after surgery. METHODS: Rates and time of local recurrence of spinal schwannoma were quantified. Predictive value of various clinical factors was assessed, including age, gender, tumor size, affected spinal segment, and type of surgery. Descriptive statistics and univariate regression analyses were performed. RESULTS: Nine (5.32%) out the 169 patients in this study experienced local recurrence approximately 1.7 years postoperatively. Univariate analyses revealed that recurrence tended to occur more often in younger patients (39.33 +/ 14.58 versus 47.01 +/- 15.29 years) and in the lumbar segment (55.56%), although this did not reach significance [hazard ratio (HR) 0.96, P = 0.127; and P = 0.195, respectively]. Recurrence also arose in the cervical and sacral spine (22.22%, respectively) but not in the thoracic area. Tumors were significantly larger in patients with recurrence (6.97 +/- 4.66 cm versus 3.81 +/- 3.34 cm), with extent in the cranial caudal direction posing the greatest hazard (HR = 1.321, P = 0.002). The location of the tumor, whether epidural, intradural, or both (P = 0.246), was not significantly related to recurrence. Regarding surgical technique, over 4 times as many patients who underwent intralesional resection experienced a recurrence proportionally to patients who underwent en bloc resection (HR = 4.178, P = 0.033). CONCLUSION: The pre-operative size of the conventional spinal schwannoma and intralesional resection are the main risk factors for local postoperative recurrence. LEVEL OF EVIDENCE: 3. PMID- 26555829 TI - Lumbar Lordosis Minus Thoracic Kyphosis: A Novel Regional Predictor for Sagittal Balance in Elderly Populations. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study is to introduce a novel regional predictor for sagittal balance in elderly populations and explore its effectiveness of evaluating sagittal balance. SUMMARY OF BACKGROUND DATA: Sagittal balance is getting increasing recognition of importance due to its significant association of health-related quality of life. However, no regional parameters could well reflect and predict the whole sagittal balance. METHODS: Medical records of elderly patients in our outpatient clinic from January 2012 to January 2014 were reviewed with standing full-spine lateral radiograph. Radiological parameters were evaluated, including max thoracic kyphosis (maxTK), max lumbar lordosis (maxLL), LL minus TK(LL-TK), PI minus LL (PI-LL), sacrum slope (SS), pelvic tilt (PT), pelvic incidence (PI), and SVA (sagittal vertical axis). Correlation analysis between SVA, LL-TK, and other radiological spinopelvic parameters and was pursued. Patients were divided into two groups according to whether patients were well-aligned in sagittal plane: Group A (well-aligned, SVA <=50 mm) and Group B (poorly aligned, SVA >50 mm), and demographic and sagittal parameters were compared. LL-TK >=0 degrees and PI LL <=13 degrees were used as a threshold value to evaluate their effectiveness of prediction for sagittal balance. RESULTS: A total of 129 patients (M: 25 and F: 104) were included in this study. SVA was significantly correlated with NRS (numeric rating scales), age, maxLL, PT, LL-TK, and PI-LL (all, P < 0.05). Age, maxTK, maxLL, SS, PT, PI, SVA, and NRS were significantly correlated with LL-TK (all P < 0.05). Significant differences were found in age, maxLL, PT, LL-TK, PI LL, SVA, and NRS between Group A (M: 15 and F: 72) and Group B (M: 10 and F: 32) (all P < 0.05). Furthermore, both LL-TK >=0 degrees and PI-LL <=13 degrees were observed in 75 patents, among which SVA <=50 mm was found in 67 patients (89%). Among patients whose LL-TK and PI-LL were <0 degrees and >13 degrees , 34 patients were poorly aligned (34/39, 87%). CONCLUSION: LL-TK was a good regional predictor for sagittal balance in elderly population, especially combined with PI LL. LEVEL OF EVIDENCE: 4. PMID- 26555830 TI - Impact of Resident Participation on Outcomes After Single-Level Anterior Cervical Diskectomy and Fusion: An Analysis of 3265 Patients from the American College of Surgeons National Surgical Quality Improvement Program Database. AB - STUDY DESIGN: Multicenter retrospective cohort study. OBJECTIVE: To investigate the relationship between resident involvement in the operating room and 30-day complication rates in patients undergoing single-level anterior cervical diskectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Although an integral part of academic medicine, surgical resident participation in the operating room and its impact on patient outcomes have been a topic of debate. No large-scale study has been performed to examine this relationship in ACDF. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was retrospectively reviewed to identify all patients who underwent single-level ACDF procedures during 2006-2013. A propensity score matching algorithm was employed to minimize baseline differences. Multivariate logistic regression analysis of unadjusted and propensity-matched cohorts was performed to examine the effect of resident participation on 30-day postoperative complication rates and length of hospital stay. RESULTS: A total of 3265 patients met inclusion criteria. The propensity score-matching procedure yielded 1003 pairs of well-matched nonresident and resident pairs. The multivariate analysis of propensity score-matched population demonstrated that resident involvement was not associated with an increased risk for any of the complications analyzed, including overall complications, medical complications, surgical complications, mortality, cardiac arrest, deep venous thrombosis, or length of total hospital stay. CONCLUSION: This large-scale, population-based study found that surgical resident participation in the operating room did not increase the risk of 30-day complications nor prolonged the length of hospital stay. Resident participation, however, was associated with an increased operative duration. Strategies to improve residents' technical proficiency outside of the operating room may enhance patient safety. LEVEL OF EVIDENCE: 3. PMID- 26555831 TI - Fatigue Performance of Cortical Bone Trajectory Screw Compared With Standard Trajectory Pedicle Screw. AB - STUDY DESIGN: Cadaveric biomechanical study. OBJECTIVE: To determine fatigue behavior of cortical bone trajectory (CBT) pedicle screws. SUMMARY OF BACKGROUND DATA: Cortical bone trajectory screws have been becoming popular in spine surgery; however, the long-term fatigue behavior of the new CBT screws remains understudied and limitations not well defined. METHODS: Twelve vertebrae from six cadaveric lumbar spines were obtained. After bone mineral density (BMD) measurements, each vertebral body was instrumented with screws from each group, that is, CBT (4.5 * 25 mm) or standard pedicle screw (6.5 * 55 mm). A load (+/- 4 Nm sagittal bending) was applied under displacement control at 1 Hz. Each construct was loaded for 100 cycles or until 6 degrees of loosening was observed. After fatigue testing, the screws were pulled out axially at 5 mm/min. RESULTS: The standard pedicle screw showed better resistance against 100 cycle loading compared with the CBT screws (P < 0.001, 6.9 degrees +/- 4.8 degrees vs. 15.2 degrees +/- 5.5 degrees , respectively). The standard pedicle screw testing usually required more than 100 cycles of loading to achieve the critical loosening (3592 +/- 4564 cycles), whereas the CBT screw never exceeded 100 cycles (84 +/- 24 cycles) (P = 0.002). Increased BMD was significantly associated with a higher number of cycles and less loosening. The standard pedicle screw group had a higher postfatigue pullout load than the CBT screw group (P = 0.001, 776 +/- 370 N and 302 +/- 232 N, respectively). CONCLUSION: The standard pedicle screw had a better fatigue performance compared with the CBT screw in vertebra with compromised bone quality. The proper insertion of the CBT screw might be prevented by the laminar anatomy depending on the screw head design. The CBT screw damaged the bone along its shaft by rotating around a fulcrum, located at either the pars, pedicle isthmus, or the junction of the pedicle and superior endplate, contingent upon the strength of the bone. PMID- 26555833 TI - Rehabilitation Following Lumbar Fusion Surgery: A Systematic Review and Meta Analysis. AB - STUDY DESIGN: A systematic review with meta-analysis. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis of current evidence evaluating the effectiveness of rehabilitation following lumbar fusion surgery (LFS). SUMMARY OF BACKGROUND DATA: LFS for the management of lower back pain, with(out) neurogenic leg pain, is increasing as the population ages. Clinical outcomes commonly lag behind surgical outcomes and 40% of patients experience significant back-related disability 12 months after LFS. Identifying rehabilitation strategies to improve function and quality of life following LFS is important. METHODS: A systematic review of databases were searched, including MEDLINE, CINAHL, and grey literature. Studies identified were screened for inclusion by title and abstract. Full text of eligible/potentially eligible studies was evaluated against predetermined eligibility criteria. Included studies were subjected to critical appraisal and risk of bias evaluation. The GRADE approach to quality of evidence was utilized. A meta-analysis comparing usual care with "complex rehabilitation," comprising exercise and cognitive behavioral therapy, for outcomes relating to pain, disability, fear of movement, and mental health was conducted at short and longer term (<3 and >12 months postsurgery) time points. RESULTS: Three studies were identified for the systematic review and 2 included in the meta-analysis (n = 237, female = 62%, mean age = 55). Low-quality evidence suggests that "complex rehabilitation" provides short-term improvement in disability [effect size, -0.85, 95% confidence interval (95% CI), -1.41 to -0.29] and fear avoidance behavior (-1.07, 95% CI 1.33, -0.80), compared with usual care. Low-quality evidence exists favoring "complex rehabilitation" over usual care for longer term disability (-0.84, 95% CI -1.11 to -0.58) and fear avoidance behavior (-1.40, 95% CI -1.69 to -1.12). CONCLUSIONS: A small number of low-quality studies suggest that "complex rehabilitation" reduces short and long-term disability and fear avoidance behavior following LFS. More, high-quality research is required to confirm the effectiveness of "complex rehabilitation" programs. PMID- 26555834 TI - A Novel Anterior Odontoid Screw Plate for C1-C3 Internal Fixation: An In Vitro Biomechanical Study. AB - STUDY DESIGN: A biomechanical in vitro study was performed using a standardized experimental protocol in a biomechanical spine testing apparatus. OBJECTIVE: The aims of this study were to evaluate the biomechanical stability afforded by 4 cervical fixation techniques: anterior cervical plate+odontoid screw+cage (ACP+OS+cage), anterior odontoid screw plate+bone graft (AOSP+bone graft), posterior C2-3 fixation+odontoid screw (C2PS+C3LMS+OS), and posterior C1-3 fixation (C1PS+C2PS+C3LMS). SUMMARY OF BACKGROUND DATA: Unstable axis injuries with multiple fracture lines are uncommon injuries, and their management is still challenging for surgeons who aim to achieve primary stability, early mobilization, preserved cervical range of motion (ROM), and favorable outcome. We designed a novel AOSP to assist in this challenging clinical scenario. METHODS: Eight fresh-frozen cadaveric spine specimens (C1-C3) were subjected to stepwise destabilization of the C1-3 complex, with serial replication of a type II Hangman fracture, a type II odontoid fracture, and a C2 to C3 disc injury. Intact specimens, destabilized specimens, and destabilized specimens with various stabilization techniques including anterior and posterior techniques, some using our AOSP, were each tested for stability. Each spine was subjected to flexion, and extension testing, left and right lateral bending, and left and right rotation. RESULTS: After AOSP+bone graft fixation, the ROMC2-C3 during all loading modes were reduced to values that were significantly less than normal. During all loading modes, AOSP+bone graft fixation significantly outperformed the ACP+OS+cage fixation in limiting ROMC2-C3. During flexion and extension, AOSP+bone graft fixation significantly outperformed the C1PS+C2PS+C3LMS fixation and C2PS+C3LMS+OS fixation in limiting ROMC2-C3. CONCLUSION: The AOSP has excellent biomechanical performance when dealing with type I Hangman fractures, type II odontoid fractures, and C2-3 disc injuries. The AOSP+one graft fixation can preserve the function of atlanto-axial joint, which may be a valuable stabilization strategy for these unique injuries. PMID- 26555835 TI - Impact of Axial Neck Pain on Quality of Life After Laminoplasty. AB - STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to elucidate the impact of axial pain following cervical laminoplasty on health related quality of life (HRQOL). SUMMARY OF BACKGROUND DATA: Axial neck pain is a frequently encountered complication after laminoplasty. However, limited information is available regarding the time-dependent changes in axial pain and the impact of this pain on clinical outcomes, including HRQOL. METHODS: One hundred sixty-two consecutive patients with cervical myelopathy underwent double door laminoplasty using hydroxyapatite spacers from 2008 to 2012. The outcome measures included the Japanese Orthopaedic Association score (JOA score), the EuroQol 5 Dimension Questionnaire (EQ-5D), and the Short Form-36 survey (SF-36). The intensity of axial pain was assessed using an 11-point numerical rating scale (NRS). These assessments were conducted preoperatively and at 6-month, 1-year, and 2-year follow-ups. Patient satisfaction with outcome was graded using a 7 point NRS at the 2-year follow-up. RESULT: One hundred twenty-one patients completed the 2-year follow-up. The mean axial pain intensity decreased slightly over time; however, the decrease was not significant. The JOA score, EQ-5D score, and all SF-36 domains, excluding general health perceptions, improved significantly compared with baseline levels at the 6-month follow-up or later. Baseline axial pain intensity showed a significant negative correlation with baseline HRQOL only in the SF-36 bodily pain domain. In contrast, axial pain intensity showed significant negative correlations with all HRQOL measures at the 6-month follow-up. At the 2-year follow-up, patients with an axial pain intensity >=3 showed significantly worse outcomes than did patients with a pain intensity <3 in the EQ-5D score, SF-36 score, and patient satisfaction grades, but not in the JOA score. CONCLUSION: Axial neck pain has a significant negative impact on clinical outcomes, including a wide range of HRQOL measures and patient satisfaction with outcome, in patients undergoing conventional double-door laminoplasty. LEVEL OF EVIDENCE: 3. PMID- 26555836 TI - Pediatric Cervical Spine and Spinal Cord Injury: A National Database Study. AB - STUDY DESIGN: A retrospective administrative database analysis. OBJECTIVE: The aim of this study was to investigate the incidence and characteristics of pediatric cervical spine injury (PCSI) utilizing the Kids' Inpatient Database (KID). SUMMARY OF BACKGROUND DATA: PCSI is debilitating, but comprehensive analyses have been difficult due to its rarity. There have been a few database studies on PCSI; however, the studies employed databases that suffer from selection bias. METHODS: The triennial KID was queried from years 2000 to 2012 using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Pediatric admissions were divided into five age groups reflecting different developmental stages. PCSI was analyzed in terms of trend, demographics, injury characteristics, hospital characteristics, comorbidities, and outcomes variables. Multivariate logistic regression analyses were used to identify independent risk factors for PCSI among trauma admissions and to identify independent risk factors for mortality among PCSI admissions. RESULTS: Over the past decade, the overall prevalence of traumatic PCSI was 2.07%, and the mortality rate was 4.87%. Most frequent cause of PCSI was transportation accidents, accounting for 57.51%. Upper cervical spine injury (C1 C4), cervical fracture with spinal cord injury, spinal cord injury without radiographic abnormality (SCIWORA), and dislocation showed a decreasing trend with age. Some comorbidities, including, but not limited to, fluid and electrolyte disorders, and paralysis were common across all age groups, while substance abuse showed a bimodal distribution. Independent risk factors for PCSI after trauma were older cohorts, non-Northeast region, and transportation accidents. For mortality after PCSI, independent risk factors were younger cohorts, transportation accidents, upper cervical spine injury, dislocation, and spinal cord injuries. Median length of stay and cost were 3.84 days and $14 742. CONCLUSION: Pediatric patients are highly heterogeneous, constantly undergoing behavioral, environmental, and anatomical changes. PCSI after trauma is more common among older cohorts; however, mortality after sustaining PCSI is higher among younger patients. LEVEL OF EVIDENCE: 4. PMID- 26555837 TI - Prolonged Hoarseness Caused by Arytenoid Dislocation After Anterior Cervical Corpectomy and Fusion. AB - STUDY DESIGN: A case of arytenoid dislocation after anterior cervical corpectomy and fusion (ACCF) is reported. OBJECTIVE: To emphasize that arytenoid dislocation could be a possible cause of prolonged hoarseness in patients after ACCF. SUMMARY OF BACKGROUND: Prolonged hoarseness is a common postoperative complication of cervical surgeries, especially in the anterior approach. Postoperative hoarseness is usually associated with paresis of the recurrent laryngeal nerve (RLN). However, other causes such as arytenoids dislocation, which is often misdiagnosed as RLN palsy, should not be ignored either. METHODS: We reported one case of arytenoid dislocation after ACCF and reviewed the related literatures. RESULTS: One patient treated with ACCF experienced prolonged postoperative hoarseness. Arytenoid dislocation was confirmed by laryngoscopy examination and three dimensional computed tomography (CT) scan. To deal with the problem, a closed reduction of cricoarytenoid joint was performed under general anesthesia. Fortunately, the motion of vocal fold became nearly back to normal after surgery and the patient recovered uneventfully. He was satisfied with the clinical outcome at the final follow-up. CONCLUSION: Arytenoid dislocation should never be ignored in the differential diagnosis of prolonged postoperative hoarseness after ACCF. This situation can be confirmed by CT scan, vocal cord electromyography (EMG), fiberoptic laryngoscopy, or strobovideolaryngoscopy. Once the diagnosis is established, appropriate treatment should be considered immediately. LEVEL OF EVIDENCE: 3. PMID- 26555838 TI - The Influence of Insurance Status on the Surgical Treatment of Acute Spinal Fractures. AB - STUDY DESIGN: A retrospective, propensity score, multivariate analysis of the National Trauma Data Bank (NTDB) between 2008 and 2011. OBJECTIVE: The aim of this study was to determine the relationship between insurance status and rates of surgery for acute spinal fractures with and without spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: The decision for surgery in patients with spinal fractures is often based on fracture pattern and stability, associated SCI, and the presence of ligamentous and other associated injuries. It is poorly understood how nonclinical factors, such as insurance status, influence the decision for surgical intervention in patients sustaining spinal trauma. METHODS: Using NTDB admission years 2008 to 2011, we included patients 18 to 64 years old who sustained a fracture of the cervical or thoracolumbar spine. Patients were excluded if they sustained polytrauma (Injury Severity Score >=27) or a major injury (Abbreviated Injury Scale severity >=3) to the head, thorax, or abdomen. Our main outcome measure was surgical versus nonsurgical treatment for spinal injury; our main predictor was insurance status. Hierarchical multivariate regression analysis and propensity scores were used to determine the relationship between insurance status and surgical treatment, controlling for other factors. We calculated adjusted odds ratios (ORs) for rates of surgery. RESULTS: Our propensity score multivariate analysis demonstrated significantly higher rates of surgery in patients with SCI (OR = 11.76, P < 0.001), insurance (OR = 1.27, P < 0.001), white (OR = 1.21, P = 0.018) versus black race, blunt trauma (OR = 5.63, P < 0.001), shock (OR = 1.62, P < 0.001), higher Glasgow Coma Scale (GCS) score (OR = 1.02, P = 0.002), transfer from lower acuity hospital (OR = 1.51, P < 0.001), and treatment at teaching hospitals (OR = 1.49, P < 0.001). Multivariable subgroup analysis of SCI patients similarly revealed higher surgical rates for insured patients (OR = 1.46, P < 0.001) than those without insurance. CONCLUSION: Patients with traumatic spine fractures were more likely to receive surgery if they were insured, regardless of the presence of SCI. PMID- 26555839 TI - Minimally Invasive Versus Open Laminectomy for Lumbar Stenosis: A Systematic Review and Meta-Analysis. AB - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVE: To assess the relative merits of minimally invasive unilateral laminectomy for bilateral decompression (ULBD) versus open laminectomy, a systematic review and meta analysis of all available evidence was performed. SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis is one of the most common pathologies in the increasingly elderly population that results in claudication, back and leg pain, and disability. The conventional approach for decompression is open laminectomy. In recent years, there has been a surge in microendoscopic procedures, which aim to minimize invasiveness. Despite the increasing use of these minimally invasive techniques, few studies have directly compared the safety, efficacy, and outcomes of these procedures with conventional laminectomy. There is a lack of robust clinical evidence, with most reports limited to single-center, inadequately powered, noncomparative studies. METHODS: Relevant articles were identified from six electronic databases. Predefined endpoints were extracted and meta-analyzed from the identified studies. RESULTS: Satisfaction rates were significantly higher in the minimally invasive group (84% vs. 75.4%; P = 0.03), whereas back pain Visual Analog Scale scores were lower (P < 0.00001). Minimally invasive laminectomy operative duration was 11 minutes longer than the open approach (P = 0.001), however this may not have clinical significance. However, there was less blood loss (P < 0.00001) and shorter hospital stay (2.1 days; P < 0.0001). Dural injuries and cerebrospinal fluid leaks were comparable, but reoperation rates were lower in the minimally invasive cohort (1.6% vs. 5.8%; P = 0.02); however this was not significant when only randomized evidence was considered. CONCLUSION: The pooled evidence suggests ULBD may be associated with less blood loss and shorter stay, with similar complication profiles to the open approach. These findings warrant verification in large prospective registries and randomized trials. LEVEL OF EVIDENCE: 1. PMID- 26555840 TI - Isolation and Characterization of Human Mesenchymal Stem Cells From Facet Joints and Interspinous Ligaments. AB - STUDY DESIGN: A descriptive in vitro study on isolation and differentiation of human mesenchymal stem cells (MSCs) derived from the facet joints and interspinous ligaments. OBJECTIVE: To isolate cells from the facet joints and interspinous ligaments and investigate their surface marker profile and differentiation potentials. SUMMARY OF BACKGROUND DATA: Lumbar spinal canal stenosis and ossification of the posterior longitudinal ligament are progressive conditions characterized by the hypertrophy and ossification of ligaments and joints within the spinal canal. MSCs are believed to play a role in the advancement of these diseases and the existence of MSCs has been demonstrated within the ligamentum flavum and posterior longitudinal ligament. The aim of this study was to investigate whether these cells could also be found within facet joints and interspinous ligaments. METHODS: Samples were harvested from 10 patients undergoing spinal surgery. The MSCs from facet joints and interspinous ligaments were isolated using direct tissue explant technique. Cell surface antigen profilings were performed via flow cytometry. Their lineage differentiation potentials were analyzed. RESULTS: The facet joints and interspinous ligaments-derived MSCs have the tri-lineage potential to be differentiated into osteogenic, adipogenic, and chondrogenic cells under appropriate inductions. Flow cytometry analysis revealed both cell lines expressed MSCs markers. Both facet joints and interspinous ligaments-derived MSCs expressed marker genes for osteoblasts, adipocytes, and chondrocytes. CONCLUSION: The facet joints and interspinous ligaments may provide alternative sources of MSCs for tissue engineering applications. The facet joints and interspinous ligaments-derived MSCs are part of the microenvironment of the human ligaments of the spinal column and might play a crucial role in the development and progression of degenerative spine conditions. PMID- 26555841 TI - Two-Nation Comparison of Classification and Treatment of Thoracolumbar Fractures: An Internet-Based Multicenter Study Among Spine Surgeons. AB - STUDY DESIGN: Web-based multicenter study. OBJECTIVE: The aim of the study was to assess and compare the management strategy for traumatic thoracolumbar fractures between German and Dutch spine surgeons. SUMMARY OF BACKGROUND DATA: To date, there is no evidence-based treatment algorithm for thoracolumbar spine fractures, thereby an international controversy concerning optimal treatment exists. METHODS: In this web-based multicenter study (www.spine.hostei.com), computed tomography scans of traumatic thoracolumbar fractures (T12-L2) were evaluated by German and Dutch spine surgeons. Supplementary case-specific information such as age, sex, height, weight, neurological status, and injury mechanism were provided.By using a questionnaire, fractures were classified according to the AO Magerl Classification, followed by 6 questions concerning the treatment algorithm. Data were analyzed using SPSS (Version 21, 76, Chicago, IL). The interobserver agreement was determined by using Cohen kappa. Statistical significance was defined as P < 0.05. RESULTS: Twelve surgeons (6 per country) evaluated each 91 cases. The fractures were classified as AO Type A in 82% (898 votes), Type B in 14% (150 votes), and Type C in 4% (44 votes). No significant difference concerning the AO Classification between German and Dutch spine surgeons was found. Overall German spine surgeons had a lower threshold concerning the indication for surgical treatment (Ger 87% vs. NL 30%; P < 0.05). There was a consensus about operative stabilization of AO Type B and C injuries and injuries with neurologic deficit, whereas a discrepancy in the therapeutic algorithm for AO Type A fractures was observed. This difference was most pronounced regarding the indication for posterior (Ger 96.6%; NL 41.2%; P < 0.05) and circumferential stabilization (Ger 53.4%; NL 0%; P < 0.05) for burst fractures. CONCLUSION: There is a consensus to stabilize AO Type B and C fractures, whereas country-specific differences in the treatment of Type A fractures, especially in case of burst fractures, occur. Prospective, controlled multicenter outcome studies may provide more evidence in optimal treatment for thoracolumbar fractures. LEVEL OF EVIDENCE: 2. PMID- 26555842 TI - Neurologic Complications, Reoperation, and Clinical Outcomes After Surgery for Vertebral Osteomyelitis. AB - STUDY DESIGN: A consecutive retrospective cohort study from 2008 to 2013 at a single tertiary-care institution was conducted. OBJECTIVE: The aim of the study was to characterize recovery from pain and neurologic deficit after surgery for vertebral osteomyelitis (VO), and identify incidence of postoperative adverse events. SUMMARY OF BACKGROUND DATA: A minority of patients with VO require surgery. Although prior studies have characterized outcomes after medical management, the morbidity after surgery is poorly defined. METHODS: The primary outcome was change from baseline in a Modified McCormick Scale (MMS, 1-5 scale), whereas secondary outcomes included reoperation and change in self-reported pain Visual Analog Scale (VAS, 0-10 scale). MMS and VAS were collected throughout the postoperative course as surrogates for neurologic function and degree of pain. Intraoperative, short-term postoperative (<30 d), and long-term neurologic complications were recorded. New-onset neurologic deficits in the postoperative period were considered neurologic complications. RESULTS: Fifty patients were included; a majority (52%) presented with a neurologic deficit. The median length of follow-up was 18 months. A statistically significant improvement in MMS was observed by 12 months postoperatively, whereas an improvement in VAS was observed by 3 months. The mean improvement in MMS at last follow-up was 0.35, whereas the mean improvement in VAS was 3.40. One quarter of patients required reoperation. At 24 months postoperatively, 10% died, 26% underwent reoperation, 42% experienced a neurologic complication, and 60% experienced at least one of these 3 adverse events. CONCLUSION: This is the first study to investigate neurologic complications, reoperation, and pain in a longitudinal manner after surgery for VO. We observed statistically significant improvements in MMS and VAS in the postoperative period. Despite these improvements, the 24-month incidence of overall adverse events was 60%. Patients and clinicians should be aware of the clinical improvement but high incidence of adverse events after surgical management of VO. LEVEL OF EVIDENCE: 4. PMID- 26555843 TI - Is the step-wise tiered approach for ERA of pharmaceuticals useful for the assessment of cancer therapeutic drugs present in marine environment? AB - Methotrexate (MTX) and tamoxifen (TMX) cancer therapeutic drugs have been detected within the aquatic environment. Nevertheless, MTX and TMX research is essentially bio-medically orientated, with few studies addressing the question of its toxicity in fresh water organisms, and none to its' effect in the marine environment. To the authors' knowledge, Environmental Risk Assessments (ERA) for pharmaceuticals has mainly been designed for freshwater and terrestrial environments (European Medicines Agency-EMEA guideline, 2006). Therefore, the purpose of this research was (1) to assess effect of MTX and TMX in marine organism using the EMEA guideline, (2) to develop an ERA methodology for marine environment, and (3) to evaluate the suitability of including a biomarker approach in Phase III. To reach these aims, a risk assessment of MTX and TMX was performed following EMEA guideline, including a 2-tier approach during Phase III, applying lysosomal membrane stability (LMS) as a screening biomarker in tier-1 and a battery of biochemical biomarkers in tier-2. Results from Phase II indicated that MTX was not toxic for bacteria, microalgae and sea urchin at the concentrations tested, thus no further assessment was required, while TMX indicated a possible risk. Therefore, Phase III was performed for only TMX. Ruditapes philippinarum were exposed during 14 days to TMX (0.1, 1, 10, 50 MUg L( 1)). At the end of the experiment, clams exposed to environmental concentration indicated significant changes in LMS compared to the control (p<0.01); thus a second tier was applied. A significant induction of biomarkers (activity of Ethoxyresorufin O-deethylase [EROD], glutathione S-transferase [GST], glutathione peroxidase [GPX], and lipid peroxidation [LPO] levels) was observed in digestive gland tissues of clams compared with control (p<0.01). Finally, this study indicated that MTX was not toxic at an environmental concentration, whilst TMX was potentially toxic for marine biota. This study has shown the necessity to create specific guidelines in order to evaluate effects of pharmaceuticals in marine environment which includes sensitive endpoints. The inadequacy of current EMEA guideline to predict chemotherapy agents toxicity in Phase II was displayed whilst the usefulness of other tests were demonstrated. The 2-tier approach, applied in Phase III, appears to be suitable for an ERA of cancer therapeutic drugs in the marine environment. PMID- 26555844 TI - Moment equations in spatial evolutionary ecology. AB - How should we model evolution in spatially structured populations? Here, I review an evolutionary ecology approach based on the technique of spatial moment equations. I first provide a mathematical underpinning to the derivation of equations for the densities of various spatial configurations in network-based models. I then show how this spatial ecological framework can be coupled with an adaptive dynamics approach to compute the invasion fitness of a rare mutant in a resident population at equilibrium. Under the additional assumption that mutations have small phenotypic effects, I show that the selection gradient can be expressed as a function of neutral measures of genetic and demographic structure. I discuss the connections between this approach and inclusive fitness theory, as well as the applicability and limits of this technique. My main message is that spatial moment equations can be used as a means to obtain compact qualitative arguments about the evolution of life-history traits for a variety of life cycles. PMID- 26555845 TI - Toward an optimal design principle in symmetric and asymmetric tree flow networks. AB - Fluid flow in tree-shaped networks plays an important role in both natural and engineered systems. This paper focuses on laminar flows of Newtonian and non Newtonian power law fluids in symmetric and asymmetric bifurcating trees. Based on the constructal law, we predict the tree-shaped architecture that provides greater access to the flow subjected to the total network volume constraint. The relationships between the sizes of parent and daughter tubes are presented both for symmetric and asymmetric branching tubes. We also approach the wall-shear stresses and the flow resistance in terms of first tube size, degree of asymmetry between daughter branches, and rheological behavior of the fluid. The influence of tubes obstructing the fluid flow is also accounted for. The predictions obtained by our theory-driven approach find clear support in the findings of previous experimental studies. PMID- 26555846 TI - A stochastic mechanism for signal propagation in the brain: Force of rapid random fluctuations in membrane potentials of individual neurons. AB - There are two functionally important factors in signal propagation in a brain structural network: the very first synaptic delay-a time delay about 1ms-from the moment when signals originate to the moment when observation on the signal propagation can begin; and rapid random fluctuations in membrane potentials of every individual neuron in the network at a timescale of microseconds. We provide a stochastic analysis of signal propagation in a general setting. The analysis shows that the two factors together result in a stochastic mechanism for the signal propagation as described below. A brain structural network is not a rigid circuit rather a very flexible framework that guides signals to propagate but does not guarantee success of the signal propagation. In such a framework, with the very first synaptic delay, rapid random fluctuations in every individual neuron in the network cause an "alter-and-concentrate effect" that almost surely forces signals to successfully propagate. By the stochastic mechanism we provide analytic evidence for the existence of a force behind signal propagation in a brain structural network caused by rapid random fluctuations in every individual neuron in the network at a timescale of microseconds with a time delay of 1ms. PMID- 26555848 TI - Fast ion conductivity in strained defect-fluorite structure created by ion tracks in Gd2Ti2O7. AB - The structure and ion-conducting properties of the defect-fluorite ring structure formed around amorphous ion-tracks by swift heavy ion irradiation of Gd2Ti2O7 pyrochlore are investigated. High angle annular dark field imaging complemented with ion-track molecular dynamics simulations show that the atoms in the ring structure are disordered, and have relatively larger cation-cation interspacing than in the bulk pyrochlore, illustrating the presence of tensile strain in the ring region. Density functional theory calculations show that the non-equilibrium defect-fluorite structure can be stabilized by tensile strain. The pyrochlore to defect-fluorite structure transformation in the ring region is predicted to be induced by recrystallization during a melt-quench process and stabilized by tensile strain. Static pair-potential calculations show that planar tensile strain lowers oxygen vacancy migration barriers in pyrochlores, in agreement with recent studies on fluorite and perovskite materials. In view of these results, it is suggested that strain engineering could be simultaneously used to stabilize the defect-fluorite structure and gain control over its high ion-conducting properties. PMID- 26555847 TI - Nonlinear extension of a hemodynamic linear model for coherent hemodynamics spectroscopy. AB - In this work, we are proposing an extension of a recent hemodynamic model (Fantini, 2014a), which was developed within the framework of a novel approach to the study of tissue hemodynamics, named coherent hemodynamics spectroscopy (CHS). The previous hemodynamic model, from a signal processing viewpoint, treats the tissue microvasculature as a linear time-invariant system, and considers changes of blood volume, capillary blood flow velocity and the rate of oxygen diffusion as inputs, and the changes of oxy-, deoxy-, and total hemoglobin concentrations (measured in near infrared spectroscopy) as outputs. The model has been used also as a forward solver in an inversion procedure to retrieve quantitative parameters that assess physiological and biological processes such as microcirculation, cerebral autoregulation, tissue metabolic rate of oxygen, and oxygen extraction fraction. Within the assumption of "small" capillary blood flow velocity oscillations the model showed that the capillary and venous compartments "respond" to this input as low pass filters, characterized by two distinct impulse response functions. In this work, we do not make the assumption of "small" perturbations of capillary blood flow velocity by solving without approximations the partial differential equation that governs the spatio-temporal behavior of hemoglobin saturation in capillary and venous blood. Preliminary comparison between the linear time-invariant model and the extended model (here identified as nonlinear model) are shown for the relevant parameters measured in CHS as a function of the oscillation frequency (CHS spectra). We have found that for capillary blood flow velocity oscillations with amplitudes up to 10% of the baseline value (which reflect typical scenarios in CHS), the discrepancies between CHS spectra obtained with the linear and nonlinear models are negligible. For larger oscillations (~50%) the linear and nonlinear models yield CHS spectra with differences within typical experimental errors, but further investigation is needed to assess the effect of these differences. Flow oscillations larger than 10-20% are not typically induced in CHS; therefore, the results presented in this work indicate that a linear hemodynamic model, combined with a method to elicit controlled hemodynamic oscillations (as done for CHS), is appropriate for the quantitative assessment of cerebral microcirculation. PMID- 26555849 TI - Bias due to composite reference standards in diagnostic accuracy studies. AB - Composite reference standards (CRSs) have been advocated in diagnostic accuracy studies in the absence of a perfect reference standard. The rationale is that combining results of multiple imperfect tests leads to a more accurate reference than any one test in isolation. Focusing on a CRS that classifies subjects as disease positive if at least one component test is positive, we derive algebraic expressions for sensitivity and specificity of this CRS, sensitivity and specificity of a new (index) test compared with this CRS, as well as the CRS based prevalence. We use as a motivating example the problem of evaluating a new test for Chlamydia trachomatis, an asymptomatic disease for which no gold standard test exists. As the number of component tests increases, sensitivity of this CRS increases at the expense specificity, unless all tests have perfect specificity. Therefore, such a CRS can lead to significantly biased accuracy estimates of the index test. The bias depends on disease prevalence and accuracy of the CRS. Further, conditional dependence between the CRS and index test can lead to over-estimation of index test accuracy estimates. This commonly-used CRS combines results from multiple imperfect tests in a way that ignores information and therefore is not guaranteed to improve over a single imperfect reference unless each component test has perfect specificity, and the CRS is conditionally independent of the index test. When these conditions are not met, as in the case of C. trachomatis testing, more realistic statistical models should be researched instead of relying on such CRSs. PMID- 26555851 TI - Health in the Context of Global Health. PMID- 26555850 TI - The Effects of 17 Weeks of Ballet Training on the Autonomic Modulation, Hormonal and General Biochemical Profile of Female Adolescents. AB - This study aimed to examine the alterations in physiological and biochemical markers, after 17 weeks of ballet training in high level ballet dancers. Twenty four female ballet dancers from 12 to 15 years old took part in the study. The study followed 17 weeks of ballet training and analyzed changes in body composition, the autonomic nervous system and biochemical variables before and after (post) training. The internal training load was obtained using the session rating of perceived exertion (session-RPE) method, calculated as the mean weekly session-RPE, monotony and strain. After 17 weeks of training there were significant increases in body mass, height, lean body mass, total protein, urea, hemoglobin concentration, testosterone and thyroxine. During this period, decreases in relative body fat, uric acid, red blood cells, C-reactive protein, and ferritin were also found. After the training period, the autonomic modulation demonstrated significant positive alterations, such as increases in parasympathetic related indices. Based on the results obtained we concluded that ballet training led to improvements in body composition and autonomic modulation. In general hematological and biochemical variables demonstrated that the training did not have adverse effects on the health state of the adolescents. PMID- 26555852 TI - C and N Hybrid Coordination Derived Co-C-N Complex as a Highly Efficient Electrocatalyst for Hydrogen Evolution Reaction. AB - Development of an efficient hydrogen evolution reaction (HER) catalyst composed of earth-abundant elements is scientifically and technologically important for the water splitting associated with the conversion and storage of renewable energy. Herein we report a new class of Co-C-N complex bonded carbon (only 0.22 at% Co) for HER with a self-supported and three-dimensional porous structure that shows an unexpected catalytic activity with low overpotential (212 mV at 100 mA cm(-2)) and long-term stability, better than that of most traditional-metal catalysts. Experimental observations in combination with density functional theory calculations reveal that C and N hybrid coordination optimizes the charge distribution and enhances the electron transfer, which synergistically promotes the proton adsorption and reduction kinetics. PMID- 26555854 TI - One pass learning for generalized classifier neural network. AB - Generalized classifier neural network introduced as a kind of radial basis function neural network, uses gradient descent based optimized smoothing parameter value to provide efficient classification. However, optimization consumes quite a long time and may cause a drawback. In this work, one pass learning for generalized classifier neural network is proposed to overcome this disadvantage. Proposed method utilizes standard deviation of each class to calculate corresponding smoothing parameter. Since different datasets may have different standard deviations and data distributions, proposed method tries to handle these differences by defining two functions for smoothing parameter calculation. Thresholding is applied to determine which function will be used. One of these functions is defined for datasets having different range of values. It provides balanced smoothing parameters for these datasets through logarithmic function and changing the operation range to lower boundary. On the other hand, the other function calculates smoothing parameter value for classes having standard deviation smaller than the threshold value. Proposed method is tested on 14 datasets and performance of one pass learning generalized classifier neural network is compared with that of probabilistic neural network, radial basis function neural network, extreme learning machines, and standard and logarithmic learning generalized classifier neural network in MATLAB environment. One pass learning generalized classifier neural network provides more than a thousand times faster classification than standard and logarithmic generalized classifier neural network. Due to its classification accuracy and speed, one pass generalized classifier neural network can be considered as an efficient alternative to probabilistic neural network. Test results show that proposed method overcomes computational drawback of generalized classifier neural network and may increase the classification performance. PMID- 26555853 TI - The impact of off-pump surgery in end-organ function: practical end-points. AB - Most surgeons perform coronary bypass surgery with the aid of cardiopulmonary bypass, which inflicts a massive systemic inflammatory response to the body leading to adverse clinical outcome. In an attempt to make CABG less invasive, interest have been diverted to the off pump technique.The current review attempts to bring an insight onto the last ten years knowledge on the off-pump impact in end organ function, with an aim to draw some clear conclusions in order to allow practitioners to reflect on the subject. PMID- 26555855 TI - A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening. AB - We demonstrate a new drug screening method for determining the binding affinity of small drug molecules to a target protein by forming fluorescent gold nanoclusters (Au NCs) within the drug-loaded protein, based on the differential fluorescence signal emitted by the Au NCs. Albumin proteins such as human serum albumin (HSA) and bovine serum albumin (BSA) are selected as the model proteins. Four small molecular drugs (e.g., ibuprofen, warfarin, phenytoin, and sulfanilamide) of different binding affinities to the albumin proteins are tested. It was found that the formation rate of fluorescent Au NCs inside the drug loaded albumin protein under denaturing conditions (i.e., 60 degrees C or in the presence of urea) is slower than that formed in the pristine protein (without drugs). Moreover, the fluorescent intensity of the as-formed NCs is found to be inversely correlated to the binding affinities of these drugs to the albumin proteins. Particularly, the higher the drug-protein binding affinity, the slower the rate of Au NCs formation, and thus a lower fluorescence intensity of the resultant Au NCs is observed. The fluorescence intensity of the resultant Au NCs therefore provides a simple measure of the relative binding strength of different drugs tested. This method is also extendable to measure the specific drug-protein binding constant (KD) by simply varying the drug content preloaded in the protein at a fixed protein concentration. The measured results match well with the values obtained using other prestige but more complicated methods. PMID- 26555856 TI - Prenatal Versus Postnatal Tobacco Smoke Exposure and Intensive Care Use in Children Hospitalized With Bronchiolitis. AB - OBJECTIVE: Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU). METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used chi-square, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression. RESULTS: Among 2207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, and 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.14-2.00). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95, 95% CI 1.13-3.37) compared to children without postnatal tobacco smoke exposure (aOR 1.47, 95% CI 1.05-2.04). CONCLUSIONS: Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages. PMID- 26555857 TI - Applicability of the pre-death grief concept to dementia family caregivers in Asia. AB - OBJECTIVE: Pre-death grief is prevalent among dementia family caregivers. When unaddressed, it produces adverse outcomes. With its research primarily conducted in Caucasians, its applicability to non-Caucasians is uncertain. We explore the existence and the characteristics of pre-death grief in a multi-ethnic Asian population using an established pre-death grief scale-Marwit-Meuser Caregiver Grief Inventory (MM-CGI). METHODS: Seventy-two dementia family caregivers were recruited from a tertiary hospital. Existence of pre-death grief was shown by its measurability on MM-CGI, together with good internal consistency reliability and construct validity. Characteristics of pre-death grief were explored through multivariate linear regression of MM-CGI and by comparing MM-CGI scores with those from the original US study using one-sample T-test. RESULTS: In the Asian context, pre-death grief was measurable in a reliable and valid manner. Risk factors of pre-death grief included caring for patients with severe dementia, spousal relationship and secondary or below education. Influence of culture was palpable-Asians had more worries and felt isolation, and certain ethnicity showed more pre-death grief. CONCLUSIONS: Pre-death grief is applicable even to the non Caucasian population. It bears much similarity to that in Caucasians. Yet, its expression is modified by culture. Clinicians working with non-Caucasian populations need to be sensitive to its presence and to the influence of culture on its expression. (c) 2015 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. PMID- 26555858 TI - Stimulus-response correspondence effect as a function of temporal overlap between relevant and irrelevant information processing. AB - The stimulus-response correspondence (SRC) effect refers to advantages in performance when stimulus and response correspond in dimensions or features, even if the common features are irrelevant to the task. Previous research indicated that the SRC effect depends on the temporal course of stimulus information processing. The current study investigated how the temporal overlap between relevant and irrelevant stimulus processing influences the SRC effect. In this experiment, the irrelevant stimulus (a previously associated tone) preceded the relevant stimulus (a coloured rectangle). The irrelevant and relevant stimuli onset asynchrony was varied to manipulate the temporal overlap between the irrelevant and relevant stimuli processing. Results indicated that the SRC effect size varied as a quadratic function of the temporal overlap between the relevant stimulus and irrelevant stimulus. This finding extends previous experimental observations that the SRC effect size varies in an increasing or decreasing function with reaction time. The current study demonstrated a quadratic function between effect size and the temporal overlap. PMID- 26555859 TI - Ecosystem service information to benefit sustainability standards for commodity supply chains. AB - The growing base of information about ecosystem services generated by ecologists, economists, and other scientists could improve the implementation, monitoring, and evaluation of commodity-sourcing standards being adopted by corporations to mitigate risk in their supply chains and achieve sustainability goals. This review examines various ways that information about ecosystem services could facilitate compliance with and auditing of commodity-sourcing standards. We also identify gaps in the current state of knowledge on the ecological effectiveness of sustainability standards and demonstrate how ecosystem-service information could complement existing monitoring efforts to build credible evidence. This paper is a call to the ecosystem-service scientists to engage in this decision context and tailor the information they are generating to the needs of the standards community, which we argue would offer greater efficiency of standards implementation for producers and enhanced effectiveness for standard scheme owners and corporations, and should thus lead to more sustainable outcomes for people and nature. PMID- 26555860 TI - Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning. AB - The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation. PMID- 26555861 TI - Apoptotic Effect of Sanggenol L via Caspase Activation and Inhibition of NF kappaB Signaling in Ovarian Cancer Cells. AB - In the present study, the underlying apoptotic mechanism of sanggenol L was elucidated in ovarian cancer cells. Sanggenol L showed cytotoxic and antiproliferative effect in A2780, SKOV-3, and OVCAR-3 ovarian cancer cells in a concentration-dependent fashion. Consistently, sanggenol L increased sub-G1 phase population and early and late apoptotic portion in ovarian cancer cells. Also, sanggenol L activated caspase9/3, suppressed the phosphorylation of IkappaBalpha and p65 NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), attenuated the expression of Cyclin D1, and cleaved poly(adenosine diphosphate ribose -ribose) polymerase in SKOV-3, A2780, and OVCAR-3 cells. Furthermore, sanggenol L blocked nuclear translocation of NF-kappaB and also attenuated the expression of NF-kappaB related genes such as c-Myc, Cyclin D1, and Bcl-X L, Bcl-2, in lipopolysaccharide-treated SKOV-3 cells. Overall, our findings for the first time suggest that sanggenol L induces apoptosis via caspase activation and inhibition of NF-kappaB/IkappaBalpha phosphorylation as a potent chemotherapeutic agent for ovarian cancers. PMID- 26555862 TI - The efficacy and safety of sodium hyaluronate injection (Adant(r)) in treating degenerative osteoarthritis: a multi-center, randomized, double-blind, positive drug parallel-controlled and non-inferiority clinical study. AB - OBJECTIVE: To compare the efficacy and safety of two different sodium hyaluronate drugs in treating degenerative osteoarthritis (OA) of the knee. METHOD: This randomized, multi-center, double-blind, positive-drug, parallel-controlled study included 229 patients aged >= 45 years who were clinically diagnosed with degenerative OA of the knee. The patients were randomly assigned to receive for 5 consecutive weeks a once-weekly intra-articular injection of the investigational drug Adant(r), which is manufactured by fermentation, or the control drug Artz(r), which is manufactured by extraction of cockscomb. The follow-up examinations were conducted 1, 2, 3, 4 and 6 weeks after the first injection. The primary efficacy parameter was the decrease in the visual analog scale (VAS) scores of pain on movement caused by load-bearing, and the secondary efficacy parameter was the decrease in the Lequesne index. RESULTS: The intra-articular injections of Adant(r) and Artz(r) produced a significant reduction in the VAS scores for pain on movement (50.4 and 50.3 mm, respectively) and in the Lequesne index. There were no significant differences in efficacy and safety between the two drugs and non-inferiority in VAS score decreases was confirmed. CONCLUSION: The results of this study show that both Adant(r) and Artz(r) are effective for the treatment of OA and that there were no statistical differences between them in the VAS scores of pain on movement, Lequesne index or safety during the observation period with short-time follow up. PMID- 26555863 TI - Effects of aneuploidy on gene expression: implications for cancer. AB - Unbalanced chromosome content, so-called aneuploidy, is a hallmark of cancer cells. Changes in the copy numbers of chromosomes or large chromosomal regions significantly alter the expression of several hundreds of genes that are gained or lost. At the same time, aneuploidy per se affects the transcription of many genes throughout the entire genome, as several pathways are activated or inhibited in response to changes in chromosome copy number. In recent years, a large amount of quantitative genome, transcriptome and proteome data has enabled comparison of the changes in gene expression observed in aneuploid cancer cells, as well as in model aneuploid cells with defined karyotypes. Here, we summarize how aneuploidy shapes gene expression and how it may contribute to the phenotypes of cancer cells. PMID- 26555864 TI - Plasma brain-derived neurotrophic factor levels after severe traumatic brain injury. AB - OBJECTIVE: Severe traumatic brain injury (TBI) is associated with a 30-70% mortality rate. Nevertheless, in clinical practice there are no effective biomarkers for the prediction of fatal outcome following severe TBI. Therefore, the aim was to determine whether brain-derived neurotrophic factor (BDNF) plasma levels are associated with intensive care unit (ICU) mortality in patients with severe TBI. METHODS: This prospective study enrolled 120 male patients who suffered severe TBI (Glasgow Coma Scale 3-8 at emergency room admission). The plasma BDNF level was determined at ICU admission (mean 6.4 hours after emergency room admission). RESULTS: Severe TBI was associated with a 35% mortality rate and 64% of the patients presented severe TBI with multi-trauma. The mean plasma BDNF concentration among the severe TBI victims was 704.2 +/- 63.4 pg ml(-1) (+/-SEM). Nevertheless, there were no significant differences between BDNF levels in the survivor (700.2 +/- 82.8 pg ml(-1)) or non-survivor (711.6 +/- 97.4 pg ml(-1)) groups (p = 0.238) or in the isolated TBI (800.4 +/- 117.4 pg ml(-1)) or TBI with multi-trauma groups (650.5 +/- 73.9 pg ml(-1)) (p = 0.109). CONCLUSIONS: Plasma BDNF concentrations did not correlate with either short-term fatal outcome or type of injury following severe TBI. PMID- 26555865 TI - Polycycloiridals A-D, Four Iridal-Type Triterpenoids with an alpha-Terpineol Moiety from Iris tectorum. AB - Polycycloiridals A-D, four novel iridals with an unprecedented alpha-terpineol moiety resulting from cyclization of the homofarnesylside chain, were isolated from the ethanol extract of rhizomes of Iris tectorum. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configuration of 1 was determined by the modified Mosher's method and comparison of experimental and calculated electronic circular dichroism (ECD) spectrum. A possible biosynthetic pathway was postulated. PMID- 26555867 TI - Comparing the accuracy of obstetric sonography and fetal echocardiography during pediatric cardiology consultation in the prenatal diagnosis of congenital heart disease. AB - AIM: The diagnostic accuracy of fetal echocardiogram performed by an obstetrician alone and that performed jointly by an obstetrician and pediatric cardiologist for congenital heart disease were compared. MATERIALS AND METHODS: All cases of suspected fetal congenital heart disease (CHD) referred to the Prenatal Diagnostic Clinic at Tsan Yuk Hospital, Hong Kong during 2006-2011 were reviewed. Prenatal fetal echocardiogram findings were compared with postnatal diagnosis. Cases of incorrect prenatal diagnosis with significant difference in prognosis were analyzed qualitatively. RESULTS: One hundred and eleven cases of fetal CHD were analyzed. Complete agreement between prenatal and postnatal diagnosis of CHD was observed in 69.4% of cases by fetal echocardiogram performed by obstetrician and 83.8% by fetal echocardiogram performed during pediatric cardiology consultation (P = 0.001). Collaboration with a pediatric cardiologist also improved detection of ductal-dependent cardiac lesions (77.4% vs. 86%, P = < 0.001). Five cases with an incorrect diagnosis were associated with a different prognosis. Three of the cases involved outflow tract abnormalities with incorrect identification of outflow vessels. CONCLUSION: Collaboration with a pediatric cardiologist can significantly improve the accuracy of prenatal diagnosis of CHD. In particular, joint consultation is associated with significantly better detection of ductal-dependent lesions. Outflow tract abnormalities remain a diagnostic challenge in prenatal diagnosis. Incorrect identification of outflow tract vessels was the major cause of incorrect diagnosis in our series. PMID- 26555866 TI - Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin. AB - Altered phosphorylation status of the C-terminal Thr residues of Ezrin/Radixin/Moesin (ERM) is often linked to cell shape change. To determine the role of phophorylated ERM, we modified phosphorylation status of ERM and investigated changes in cell adhesion and morphology. Treatment with Calyculin-A (Cal-A), a protein phosphatase inhibitor, dramatically augmented phosphorylated ERM (phospho-ERM). Cal-A-treatment or expression of phospho-mimetic Moesin mutant (Moesin-TD) induced cell rounding in adherent cells. Moreover, reattachment of detached cells to substrate was inhibited by either treatment. Phospho-ERM, Moesin-TD and actin cytoskeleton were observed at the plasma membrane of such round cells. Augmented cell surface rigidity was also observed in both cases. Meanwhile, non-adherent KG-1 cells were rather rich in phospho-ERM. Treatment with Staurosporine, a protein kinase inhibitor that dephosphorylates phospho-ERM, up-regulated the integrin-dependent adhesion of KG-1 cells to substrate. These findings strongly suggest the followings: (1) Phospho-ERM inhibit cell adhesion, and therefore, dephosphorylation of ERM proteins is essential for cell adhesion. (2) Phospho-ERM induce formation and/or maintenance of spherical cell shape. (3) ERM are constitutively both phosphorylated and dephosphorylated in cultured adherent and non-adherent cells. PMID- 26555868 TI - An Improved-Efficiency Compact Lamp for the Thermal Infrared. AB - A major type of infrared camera is sensitive to wavelengths in the 8-14 MUm band and is mainly used for thermal imaging. Such cameras can also be used for general broadband infrared reflectance imaging when provided with a suitable light source. We report the design and properties of an infrared lamp using a heated alumina emitter suitable for active thermal infrared imaging, as well as comparisons to existing commercial light sources for this purpose. We find that the alumina lamp is a broadband non-blackbody source with a lower out-of-band emission intensity and therefore higher electrical efficiency for this application than existing commercial sources. PMID- 26555869 TI - Swedish surgical outcomes study (SweSOS): An observational study on 30-day and 1 year mortality after surgery. AB - BACKGROUND: The European Surgical Outcomes Study (EuSOS) revealed large variations in outcomes among countries. In-hospital mortality and ICU admission rates in Sweden were low, going against the assumption that access to ICU improves outcome. Long-term mortality was not reported in EuSOS and is generally poorly described in the current literature. OBJECTIVE: To describe the characteristics of the Swedish subset of EuSOS and identify predictors of short and long-term mortality after surgery. DESIGN: An observational cohort study. SETTING: Six universities and two regional hospitals in Sweden. PATIENTS: A cohort of 1314 adult patients scheduled for surgery between 4 April and 11 April 2011. MAIN OUTCOME MEASURES: 30-day and 1-year mortality. RESULTS: A total of 303 patients were lost to follow-up, leaving 1011 for analysis; 69% of patients were classified as American Society of Anesthesiologists' physical status 1 or 2, and 68% of surgical procedures were elective. The median length of stay in postanaesthesia care units (PACUs) was 175 min (interquartile range 110-270); 6.6% of patients had PACU length of stay of more than 12 h and 3.6% of patients were admitted to the ICU postoperatively. Thirty-day mortality rate was 1.8% [95% confidence interval (CI) 1.0-2.6] and 8.5% (CI 6.8-10.2) at 1 year (n = 18 and 86). The risk of death was higher than in an age and sex-matched population after 30 days (standardised mortality ratio 10.0, CI 5.9-15.8), and remained high after 1 year (standardised mortality ratio 3.9, CI 3.1-4.8). Factors predictive of 30 day mortality were age, American Society of Anesthesiologists' physical status, number of comorbidities, urgency of surgery and ICU admission. For 1-year mortality, age, number of comorbidities and urgency of surgery were independently predictive. ICU admission and long stay in PACU were not significant predictors of long-term mortality. CONCLUSION: Mortality rate increased almost five-fold at 1 year compared with 30-day mortality after surgery, demonstrating a significantly sustained long-term risk of death in this surgical population. In Sweden, factors associated with long-term postoperative mortality were age, number of comorbidities and surgical urgency. PMID- 26555870 TI - Warming before and after epidural block before general anaesthesia for major abdominal surgery prevents perioperative hypothermia: A randomised controlled trial. AB - BACKGROUND: Epidural analgesia (EDA) is known to be an independent risk factor for perioperative hypothermia and its many known adverse effects. Combined general and epidural anaesthesia decreases intraoperative core temperature more rapidly than general anaesthesia alone. Hence, adequate warming procedures are needed for these patients. OBJECTIVE: We evaluated the effects of active skin surface warming before and/or after initiation of EDA during general anaesthesia as a procedure to prevent perioperative hypothermia. DESIGN: A randomised controlled trial. SETTING: Department of Anaesthesiology in a general hospital in Germany from January 2013 until August 2014. PATIENTS: After obtaining written informed consent, we included 99 adult patients undergoing elective major abdominal surgery under combined general anaesthesia and EDA with an expected duration of surgery of at least 120 min. Patients were excluded if they were under 18 years of age, classified as American Society of Anesthesiologists' physical status 4 or higher or if patients refused EDA. INTERVENTIONS: Patients were randomly assigned to one of three groups and received either only passive insulation, 15 min of active air-forced warming after EDA and before induction of general anaesthesia, or two periods, each of 15 min, of active air-forced warming before and after EDA. Core and skin temperatures were measured at several time points throughout the study. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of hypothermia on arrival in the ICU. The secondary outcome measure was the incidence of postoperative shivering. In addition, the perioperative change in body core temperature was recorded. RESULTS: Without prewarming (n = 32), 72% of patients became hypothermic (<36 degrees C) at the end of anaesthesia. Fifteen minutes of warming after insertion of the epidural catheter and before initiation of general anaesthesia reduced the incidence of postoperative hypothermia to 6% (n = 33). After two periods of 15 min of warming before and after insertion of the epidural catheter, no patient became hypothermic (n = 34). Prewarming in either 'warming' group prevents the initial temperature drop which was observed in the control group. CONCLUSION: Warming for 15 min before and after initiation of EDA in patients receiving combined anaesthesia is effective in preventing postoperative hypothermia. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (identifier: NCT01795482). PMID- 26555871 TI - Tizanidine for the management of acute postoperative pain after inguinal hernia repair: A placebo-controlled double-blind trial. AB - BACKGROUND: alpha2-Agonists are used postoperatively as a component of multimodal analgesia. Tizanidine is a centrally acting alpha2-agonist with muscle relaxant properties. OBJECTIVE: The aim of this study was to compare the efficacy of tizanidine with placebo in terms of postoperative pain scores, analgesic consumption, return to daily activity and health-related quality of life. DESIGN: A randomised double-blind study. SETTING: Diskapi Yildirim Beyazit Training and Research Hospital. INTERVENTIONS: After obtaining ethical approval and informed patient consent, 60 patients undergoing inguinal hernia repair under general anaesthesia were randomly allocated into one of the two groups. The patients in Group T received tizanidine 4 mg orally 1 h before surgery and twice daily during the first postoperative week. The patients in Group P received the same treatment with a placebo pill. Both the groups received a standard analgesic treatment regimen comprising intravenous dexketoprofen 25 mg prior to induction of anaesthesia, dexketoprofen 25 mg orally three times daily for 1 week and intravenous paracetamol 1 g at the end of surgery. Supplemental analgesia was provided with paracetamol if the visual numerical rating scale (NRS) was at least 4 cm. MAIN OUTCOME MEASURES: Postoperative pain was assessed using the NRS. Total analgesic consumption was determined. Return to normal daily activity was evaluated using a five-point daily activity score after the first postoperative week, and health-related quality of life was evaluated using the short form-36 one month after surgery. RESULTS: The patients in Group T had significantly lower NRS pain scores than those in Group P 6, 12 and 24 h postoperatively both at rest and during movement (P < 0.001), and on postoperative days 1, 2, 3 and 4. The analgesic consumption was also lower in patients who received tizanidine. Ten patients (33%) in Group T and 23 patients (77%) in Group P consumed supplemental paracetamol (P < 0.001) after discharge. The daily activity score was lower in Group T than in Group P (P < 0.001), and the short form-36 scores were significantly different in the pain dimension [74 (74 to 100) in Group T and 74 (31 to 80) in Group P, (P < 0.001)] and in the physical component summary score. CONCLUSION: The addition of tizanidine to the postoperative pain therapy after herniorrhaphy decreased postoperative pain and analgesic consumption and improved return to normal activity and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02016443 (10 October 2013, Principal investigator D. Yazicioglu). PMID- 26555872 TI - Delayed diagnosis of anaphylaxis secondary to ondansetron: A case report. PMID- 26555873 TI - Effects of Chilling and Partial Freezing on Rigor Mortis Changes of Bighead Carp (Aristichthys nobilis) Fillets: Cathepsin Activity, Protein Degradation and Microstructure of Myofibrils. AB - To investigate the effects of chilling and partial freezing on rigor mortis changes in bighead carp (Aristichthys nobilis), pH, cathepsin B, cathepsin B+L activities, SDS-PAGE of sarcoplasmic and myofibrillar proteins, texture, and changes in microstructure of fillets at 4 degrees C and -3 degrees C were determined at 0, 2, 4, 8, 12, 24, 48, and 72 h after slaughter. The results indicated that pH of fillets (6.50 to 6.80) was appropriate for cathepsin function during the rigor mortis. For fillets that were chilled and partially frozen, the cathepsin activity in lysosome increased consistently during the first 12 h, followed by a decrease from the 12 to 24 h, which paralleled an increase in activity in heavy mitochondria, myofibrils and sarcoplasm. There was no significant difference in cathepsin activity in lysosomes between fillets at 4 degrees C and -3 degrees C (P > 0.05). Partially frozen fillets had greater cathepsin activity in heavy mitochondria than chilled samples from the 48 to 72 h. In addition, partially frozen fillets showed higher cathepsin activity in sarcoplasm and lower cathepsin activity in myofibrils compared with chilled fillets. Correspondingly, we observed degradation of alpha-actinin (105 kDa) by cathepsin L in chilled fillets and degradation of creatine kinase (41 kDa) by cathepsin B in partially frozen fillets during the rigor mortis. The decline of hardness for both fillets might be attributed to the accumulation of cathepsin in myofibrils from the 8 to 24 h. The lower cathepsin activity in myofibrils for fillets that were partially frozen might induce a more intact cytoskeletal structure than fillets that were chilled. PMID- 26555874 TI - Tinea profunda of the genital area. Successful treatment of a rare skin disease. AB - We present a rare case of 36-year-old female patient, who developed a severe Majocchi granuloma in the pubis after waxing, with isolated causative agent Trichophyton mentagrophytes. The condition was initially misdiagnosed as a bacterial folliculitis and treated unsuccessfully with topical corticosteroids and antibiotics. After the adequate diagnose was confirmed by mycological examination, followed by histopathological verification, complete remission of the symptoms was achieved at the 4th week after initiating 6 weeks course of antifungal therapy with Terbinafine 250 mg/daily dose, while good therapeutic response was observed even in the 10th day. The etiopathogenesis of the disease, as well as its current treatment options are considered, in respect to the rare occurrence of this condition in the pubic area and its frequent misdiagnosis. PMID- 26555875 TI - Pharmacogenomics considerations in the control of hypertension. AB - The response to antihypertensive therapy is very heterogeneous and the need by the physicians to account for it has driven much interest in pharmacogenomics of antihypertensive drugs. The Human Genome Project and the initiatives in genomics that followed, generated a huge number of genetic data that furnished the tools to explore the genotype-phenotype association in candidate genes and at genome wide level. In spite of the efforts and the great number of publications, pharmacogenomics of antihypertensive drugs is far from being used in clinical practice. In this review, we analyze the main findings available in PubMed from 2010 to 2015, in relation to the major classes of antihypertensive drugs. We also describe a new Phase II drug that targets two specific hypertension predisposing mechanisms. PMID- 26555876 TI - Facile biosynthesis of silver nanoparticles using Barleria cristata: mosquitocidal potential and biotoxicity on three non-target aquatic organisms. AB - Mosquitoes (Diptera: Culicidae) act as vectors of important pathogens and parasites, such as malaria, dengue, chikungunya, Japanese encephalitis and lymphatic filariasis. The use of synthetic mosquitocides often leads to high operational costs and adverse non-target effects. Recently, plant-borne compounds have been proposed for rapid extracellular biosynthesis of mosquitocidal nanoparticles. However, the impact of these nanomosquitocides against biological control agents of mosquito larval populations has been poorly studied. In this research, we biosynthesized silver nanoparticles (Ag NP) using the Barleria cristata leaf extract as a reducing and stabilizing agent. The biosynthesis of Ag NP was confirmed analyzing the excitation of surface plasmon resonance using ultraviolet-visible (UV-vis) spectrophotometry. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed the clustered and irregular shapes of Ag NP. The presence of silver was confirmed by energy dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy investigated the identity of secondary metabolites, which may also act as Ag NP capping agents. The acute toxicity of B. cristata leaf extract and biosynthesized Ag NP was evaluated against larvae of Anopheles subpictus, Aedes albopictus, and Culex tritaeniorhynchus. Compared to the leaf aqueous extract, biosynthesized Ag NP showed higher toxicity against An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus with lethal concentration (LC)50 values of 12.46, 13.49, and 15.01 MUg/mL, respectively. Notably, biosynthesized Ag NP were found safer to non-target organisms Diplonychus indicus, Anisops bouvieri, and Gambusia affinis, with respective LC50 values ranging from 633.26 to 866.92 MUg/mL. Overall, our results highlight that B. cristata-fabricated Ag NP are a promising and eco-friendly tool against young instar populations of mosquito vectors of medical and veterinary importance. PMID- 26555877 TI - Experimental evidence of negative interspecific interactions among imago fleas: flea and host identities matter. AB - We investigated interspecific interactions between two flea species (Parapulex chephrenis and Xenopsylla ramesis) via evaluation of their feeding success (the size of a blood meal and time to death after a single blood meal) when they exploited rodent hosts [Acomys cahirinus (a characteristic host of the former) or Meriones crassus (a characteristic host of the latter)] in single-species or mixed-species groups. We predicted that the negative interactions between the two fleas will result in smaller blood meals and shorter survival time in mixed- versus single-species infestations. We also predicted that the negative effect of mixed-species infestation on feeding performance would be less pronounced when fleas exploited their characteristic host rather than a non-characteristic host. When exploiting a characteristic host, P. chephrenis took larger blood meals in single- than in mixed-species groups, whereas the blood meal size in X. ramesis did not differ between treatments. When exploiting a non-characteristic host, no effect of group composition was found in either flea species. Survival time after a single blood meal was not affected by co-infestation or host species in either flea. Our results suggest context-dependence of the negative effect of co infestation on feeding performance in fleas with the manifestation of this effect varying in dependence of flea and host species identities. PMID- 26555878 TI - Early objective response may not be a prognostic factor of survival for patients with metastatic urothelial carcinoma: from a retrospective analysis of a cohort of 113 patients. AB - BACKGROUND: This study aims to better define prognostic factors for patients with metastatic urothelial carcinoma (mUC), and to identify patients who will benefit from first-line cisplatin-based chemotherapy. We test the hypothesis that early objective response (EOR), defined as the occurrence of an objective response following 2 or 3 courses of chemotherapy, could be a prognostic factor for overall survival (OS) and thus be used to guide treatment decisions. Data from 113 patients with evaluable mUC receiving first-line cisplatin-based treatment between January 2004 and December 2006 was collected retrospectively from prospectively-maintained databases across seven French cancer centers. Clinical factors potentially associated with survival and EOR were analyzed in univariate and multivariate analysis. RESULTS: One hundred three patient records were complete and available for inclusion in the multivariate model. Four factors were independently associated with OS: Performance status 1 and 2 (HR 2.3 [95 % CI 1.3 3.9], p = 0.002; HR 3.4 [95 % CI 1.6-7.2], p = 0.001 respectively); presence of visceral metastases (HR 2.2 [95 % CI 1.3-3.9], p = 0.004); abnormal hemoglobin levels (HR 1.7 [95 % CI 1.01-2.8], p = 0.045); disease progression (HR 10.1 [95 % CI 4.2-24.1], p < 0.001). CONCLUSIONS: This study confirms the prognostic factors previously reported in first-line chemotherapy for mUC. However, we failed to demonstrate that EOR was an independent predictive factor of OS. Nevertheless, an early response evaluation is recommended since early progression is an important parameter that can be used to decide whether treatment should be interrupted and changed for alternative strategies integrating the concept of personalized medicine or new immune therapies. PMID- 26555879 TI - Fetal metabolic influences of neonatal anthropometry and adiposity. AB - BACKGROUND: Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring. METHODS: Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity. RESULTS: Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant. CONCLUSION: Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures. PMID- 26555880 TI - Biosorption and degradation of decabromodiphenyl ether by Brevibacillus brevis and the influence of decabromodiphenyl ether on cellular metabolic responses. AB - There is global concern about the effects of decabromodiphenyl ether (BDE209) on environmental and public health. The molecular properties, biosorption, degradation, accumulation, and cellular metabolic effects of BDE209 were investigated in this study to identify the mechanisms involved in the aerobic biodegradation of BDE209. BDE209 is initially absorbed by wall teichoic acid and N-acetylglucosamine side chains in peptidoglycan, and then, BDE209 is transported and debrominated through three pathways, giving tri-, hepta-, octa-, and nona bromodiphenyl ethers. The C-C bond energies decrease as the number of bromine atoms on the diphenyl decreases. Polybrominated diphenyl ethers (PBDEs) inhibit protein expression or accelerate protein degradation and increase membrane permeability and the release of Cl(-), Na(+), NH4 (+), arabinose, proteins, acetic acid, and oxalic acid. However, PBDEs increase the amounts of K(+), Mg(2+), PO4 (3-), SO4 (2-), and NO3 (-) assimilated. The biosorption, degradation, accumulation, and removal efficiencies when Brevibacillus brevis (1 g L(-1)) was exposed to BDE209 (0.5 mg L(-1)) for 7 days were 7.4, 69.5, 16.3, and 94.6 %, respectively. PMID- 26555881 TI - How contamination sources and soil properties can influence the Cd and Pb bioavailability to snails. AB - To better understand the fate of metals in the environment, numerous parameters must be studied, such as the soil properties and the different sources of contamination for the organisms. Among bioindicators of soil quality, the garden snail (Cantareus aspersus) integrates multiple sources (e.g. soil, plant) and routes (e.g. digestive, cutaneous) of contamination. However, the contribution of each source on metal bioavailability and how soil properties influence these contributions have never been studied when considering the dynamic process of bioavailability. Using accumulation kinetics, this study showed that the main assimilation source of Cd was lettuce (68%), whereas the main source of Pb was the soil (90%). The plant contribution increased in response to a 2-unit soil pH decrease. Unexpectedly, an increase in the soil contribution to metal assimilation accompanied an increase in the organic matter (OM) content of the soil. For both metals, no significant excretion and influence of source on excretion have been modelled either during exposure or depuration. This study highlights how the contribution of different sources to metal bioavailability changes based on changes in soil parameters, such as pH and OM, and the complexity of the processes that modulate metal bioavailability. PMID- 26555883 TI - Erratum to: A review of the direct and indirect effects of neonicotinoids and fipronil on vertebrate wildlife. PMID- 26555882 TI - Photo-Fenton oxidation of 3-amino-5-methylisoxazole: a by-product from biological breakdown of some pharmaceutical compounds. AB - The present study aims to assess the removal of 3-amino-5-methylisoxazole (AMI), a recalcitrant by-product resulting from the biological breakdown of some pharmaceuticals, applying a solar photo-Fenton process assisted by ferrioxalate complexes (SPFF) (Fe3+/H2O2/oxalic acid/UVA-Vis) and classical solar photo-Fenton process (SPF) (Fe2+/H2O2/UVA-Vis). The oxidation ability of SPFF was evaluated at different iron/oxalate molar ratios (1:3, 1:6, and 1:9, with [total iron] = 3.58 * 10-2 mM and [oxalic acid] = 1.07 * 10-1, 2.14 * 10-1 and 3.22 * 10-1 mM, respectively) and pH values (3.5-6.5), using low iron contents (2.0 mg Fe3+ L-1). Additionally, the use of other organic ligands such as citrate and ethylenediamine-N,N'-disuccinic acid (EDDS) was tested. The oxidation power of the classical SPF was assessed at different pH values (2.8-4.0) using 2.0 mg Fe2+ per liter. Furthermore, the effect of AMI concentration (2-20 mg L-1), presence of inorganic ions (Cl-, SO42-, NO3-, HCO3-, NH4+), and radical scavengers (sodium azide and D-mannitol) on the SPF method at pH 3.5 was also assessed. Experiments were done using a lab-scale photoreactor with a compound parabolic collector (CPC) under simulated solar radiation. A pilot-scale assay was conducted using the best operation conditions. While at near neutral pH, an iron/oxalate molar ratio of 1:9 led to the removal of 72 % of AMI after 90 min of SPFF, at pH 3.5, an iron/oxalate molar ratio of 1:3 was enough to achieve complete AMI degradation (below the detection limit) after 30 min of reaction. The SPF process at pH 3.5 underwent a slower AMI degradation, reaching total AMI degradation after 40 min of reaction. The scale up of SPF process showed a good reproducibility. Oxalic and oxamic acids were identified as the main low-molecular-weight carboxylic acids detected during the pilot-scale SPF reaction. Graphical abstract ?. PMID- 26555884 TI - Effects of realistic concentrations of TiO2 and ZnO nanoparticles in Prochilodus lineatus juvenile fish. AB - The impact of nanoparticles on fish health is still a matter of debate, since nanotechnology is quite recent. In this study, freshwater benthonic juvenile fish Prochilodus lineatus were exposed through water to three concentrations of TiO2 (0.1, 1, and 10 MUg l(-1)) and ZnO (7, 70, and 700 MUg l(-1)) nanoparticles, as well as to a mixture of both (TiO2 1 MUg l(-1) + ZnO 70 MUg l(-1)) for 5 and 30 days. Nanoparticle characterization revealed an increase of aggregate size in the function of concentration, but suspensions were generally stable. Fish mortality was high at subchronic exposure to 70 and 700 MUg l(-1) of ZnO. Nanoparticle exposure led to decreased acetylcholinesterase activity either in the muscle or in the brain, depending on particle composition (muscle-TiO2 10 MUg l(-1); brain ZnO 7 and 700 MUg l(-1)), and protein oxidative damage increased in the brain (ZnO 70 MUg l(-1)) and gills (ZnO 70 MUg l(-1) and mixture) but not in the liver. Exposed fish had more frequent alterations in the liver (necrosis, vascular congestion, leukocyte infiltration, and basophilic foci) and gills (hyperplasia and epithelial damages, e.g., epithelial disorganization and epithelial loss) than the control fish. Thus, predicted concentrations of TiO2 and ZnO nanoparticles caused detectable effects on P. lineatus that may have important consequences to fish health. But, these effects are much more subtle than those usually reported in the scientific literature for high concentrations or doses of metal nanoparticles. PMID- 26555885 TI - Effects of sediment burial disturbance on macro and microelement dynamics in decomposing litter of Phragmites australis in the coastal marsh of the Yellow River estuary, China. AB - From April 2008 to November 2009, a field decomposition experiment was conducted to investigate the effects of sediment burial on macro (C, N) and microelement (Pb, Cr, Cu, Zn, Ni, and Mn) variations in decomposing litter of Phragmites australis in the coastal marsh of the Yellow River estuary. Three one-off sediment burial treatments [no sediment burial (0 mm year(-1), S0), current sediment burial (100 mm year(-1), S10), and strong sediment burial (200 mm year( 1), S20)] were laid in different decomposition sites. Results showed that sediment burials showed significant influence on the decomposition rate of P. australis, in the order of S10 (0.001990 day(-1)) ~ S20 (0.001710 day(-1)) > S0 (0.000768 day(-1)) (p < 0.05). The macro and microelement in decomposing litters of the three burial depths exhibited different temporal variations except for Cu, Zn, and Ni. No significant differences in C, N, Pb, Cr, Zn, and Mn concentrations were observed among the three burial treatments except for Cu and Ni (p > 0.05). With increasing burial depth, N, Cr, Cu, Ni, and Mn concentrations generally increased, while C, Pb, and Zn concentrations varied insignificantly. Sediment burial was favorable for C and N release from P. australis, and, with increasing burial depth, the C release from litter significantly increased, and the N in litter shifted from accumulation to release. With a few exceptions, Pb, Cr, Zn, and Mn stocks in P. australis in the three treatments evidenced the export of metals from litter to environment, and, with increasing burial depth, the export amounts increased greatly. Stocks of Cu and Ni in P. australis in the S10 and S20 treatments were generally positive, evidencing incorporation of the two metals in most sampling times. Except for Ni, the variations of C, N, Pb, Cr, Cu, Zn, and Mn stocks in P. australis in the S10 and S20 treatments were approximated, indicating that the strong burial episodes (S20) occurred in P. australis marsh in the future would have little influence on the stocks of these elements. With increasing burial depths, the P. australis was particularly efficient in binding Cu and Ni and releasing C, N, Pb, Cr, Zn, and Mn, implying that the potential eco toxic risk of Pb, Cr, Zn, and Mn exposure might be very serious. This study emphasized the effects of different burials on nutrient and metal cycling and mass balance in the P. australis marsh of the Yellow River estuary. PMID- 26555886 TI - Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. AB - OBJECTIVE: Headache is one of the most common debilitating chronic pain conditions in either active or retired military personnel with mild traumatic brain injury (MTBI). This study assessed the effect of repetitive transcranial magnetic stimulation (rTMS) in alleviating MTBI-related headache (MTBI-HA). MATERIALS AND METHOD: Veterans with MTBI-HA were randomized to receive either real rTMS (REAL group) at 10 hz for a total of 2000 pulses divided into 20 trains with one-sec inter-train interval or sham rTMS (SHAM group) at the left motor cortex (LMC) with brain magnetic resonance imaging neuronavigation guidance. Pretreatment, posttreatment one-week and four-week headache and neuropsychological assessments were conducted. RESULT: Thirty veterans were screened and twenty four (21 men and 3 women with average year-old +/- SD at 14.3 +/- 12.6) subjects' data were analyzed. A two-factor (visit * treatment) repeated measures analysis of variance (RM-ANOVA) indicated a close to significant (p = 0.06) trend of interaction between pretreatment and posttreatment one-week assessment with the intensity of the persistent daily headache decreasing from 5.7 +/- 1.9 to 2.2 +/- 2.7 and 4.6 +/- 1.3 to 3.5 +/- 2.0 for the REAL and SHAM groups, respectively. Subsequent analyses indicated REAL group demonstrated a significantly (p = 0.041) higher % of reduction in persistent headache intensity than the SHAM group (56.3 +/- 48.2% vs.15.4 +/- 43.6%) at the posttreatment one week assessment and the trend continued to the four-week assessment. Overall, a significantly (p = 0.035) higher percentage of the subjects in the REAL group (58.3%) demonstrated at least a 50% headache intensity reduction at posttreatment one-week assessment compared with the SHAM group (16.6%). The overall composite score of functionally debilitating headache exacerbation is significantly (p = 0.017) reduced in REAL group at the posttreatment four-week assessment in comparison with the SHAM group. No major sustained change in neuropsychological assessments was noted. CONCLUSION: The studied rTMS protocol appears to be a clinically feasible and effective treatment option in managing MTBI-HA. PMID- 26555888 TI - Elucidation of Molecular Identity of the W3 Locus and Its Implication in Determination of Flower Colors in Soybean. AB - The wide range of flower colors in soybean is controlled by six independent loci (W1, W2, W3, W4, Wm, and Wp). Among these loci, mutations in the W3 locus under the w4 allelic background (i.e., w3w4) produce near-white flowers, while the W3w4 genotype produces purple throat flowers. Although a gene encoding dihydroflavonol 4-reductase, DFR1, has been known to be closely associated with the W3 locus, its molecular identity has not yet been characterized. In the present study, we aimed to determine whether DFR1 is responsible for allelic variations in the W3 locus. On the basis of the sequence of a DFR probe, Glyma.14G072700 was identified as a candidate gene for DFR1, and nucleotide sequences of Glyma.14G072700 from cultivars with previously validated genotypes for the W3 locus were determined. As a result, a number of nucleotide polymorphisms, mainly single-base substitutions, between both coding and 5'-upstream region sequences of the W3 and w3 alleles were identified. Among them, an indel of 311-bp in the 5'-upstream region was noteworthy, since the Glyma.14G072700 in all the w3 alleles examined contained the indel, whereas that in all the W3 alleles did not; the former was barely expressed, but the latter was well expressed. These results suggest that Glyma.14G072700 is likely to correspond to DFR1 for the W3 locus and that its expression patterns may lead to allelic color phenotypes of W3 and w3 alleles under the w4 allelic background. PMID- 26555887 TI - Investigating the role of filamin C in Belgian patients with frontotemporal dementia linked to GRN deficiency in FTLD-TDP brains. AB - TAR DNA-binding protein 43 (TDP-43) inclusions are pathological hallmarks of patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Loss of TDP-43 in zebrafish engenders a severe muscle and vascular phenotype with a concomitant elevation of filamin C (FLNC) levels, an observation confirmed in the frontal cortex of FTLD-TDP patients. Here, we aimed to further assess the contribution of FLNC to frontotemporal dementia (FTD) etiology. We conducted a mutational screening of FLNC in a cohort of 529 unrelated Belgian FTD and FTD-ALS patients, and a control cohort of 920 unrelated and age-matched individuals. Additionally we performed an in-depth characterization of FLNC expression levels in FTD patients and a murine FTD model.In total 68 missense variants were identified of which 19 (MAF < 1%) were patient-only. Gene burden analysis demonstrated a significant association between the presence of rare variants in FLNC and disease (P = 0.0349, RR = 1.46 [95% CI 1.03-2.07]). Furthermore, elevated FLNC expression levels, observed previously in FTLD-TDP patients, were mainly attributable to FTD patients with the progranulin (GRN) p.0(IVS1 + 5G > C) loss-of-function mutation. Increased FLNC levels were, to a lesser extent, also identified in a FLNC p.V831I variant carrier and in FTD patients with the p.R159H mutation in valosin-containing protein (VCP). The GRN associated increase of FLNC was confirmed in the frontal cortex of aged Grn knockout mice starting at 16-18 months of age. Combined quantitative proteomic and bioinformatic analyses of the frontal cortex of FTD patients possessing elevated FLNC levels, identified multiple altered protein factors involved in accelerated aging, neurodegeneration and synaptogenesis.Our findings further support the involvement of aberrant FLNC expression levels in FTD pathogenesis. Identification of increased FLNC levels in aged Grn mice and impaired pathways related to aging and neurodegeneration, implies a potential role for FLNC in mediating or accelerating the aging process. PMID- 26555889 TI - Morphological, structural and biophysical properties of French and Brazilian photoaged skin. AB - BACKGROUND: Knowledge of skin biology and its alterations in different populations is very important for the development of appropriate skincare strategies. OBJECTIVES: To evaluate and compare morphological, structural and biophysical properties of photoaged skin in French and Brazilian populations, using biophysical and skin-imaging techniques. METHODS: Forty-one French and 41 Brazilian healthy, female volunteers aged between 40 and 65 years were enrolled. Each participant completed a questionnaire concerning habits related to cosmetic use, sun exposure and sun protection during different life periods. Skin on the face and volar forearm was evaluated using noninvasive techniques, to determine skin colour, transepidermal water loss (TEWL), stratum corneum water content, skin microrelief, skin viscoelasticity and dermis structure. Reflectance confocal microscopy was used to measure epidermal layer thickness and epidermal morphological and structural characteristics. RESULTS: Compared with Brazilian skin, French skin was more hydrated, had a lower TEWL and presented a distinct viscoelastic profile on the forearms and face. Brazilian facial skin was more wrinkled, and the dermis was less echogenic on the forearms and face. The French participants had thicker stratum corneum. Brazilian facial skin presented a higher prevalence of rete ridge effacement, low interkeratinocyte reflectance, huddled collagen and solar elastosis. CONCLUSIONS: Morphological, structural and biophysical differences were found when assessing the skin of the Brazilian and French participants, who were exposed to different environmental factors. PMID- 26555890 TI - Comparative genomics study for identification of putative drug targets in Salmonella typhi Ty2. AB - Typhoid presents a major health concern in developing countries with an estimated annual infection rate of 21 million. The disease is caused by Salmonella typhi, a pathogenic bacterium acquiring multiple drug resistance. We aim to identify proteins that could prove to be putative drug targets in the genome of S. typhi str. Ty2. We employed comparative and subtractive genomics to identify targets that are absent in humans and are essential to S. typhi Ty2. We concluded that 46 proteins essential to pathogen are absent in the host genome. Filtration on the basis of drug target prioritization singled out 20 potentially therapeutic targets. Their absence in the host and specificity to S. typhi Ty2 makes them ideal targets for treating typhoid in Homo sapiens. 3D structures of two of the final target enzymes, MurA and MurB have been predicted via homology modeling which are then used for a docking study. PMID- 26555891 TI - Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction. AB - Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 uM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO*) levels over those found in the presence of ethanol alone, disappeared upon blocking NO* synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO* donor sodium nitroprusside (10 uM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO* as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO* availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without significantly disrupting endothelium-independent, alcohol induced cerebral artery constriction itself. PMID- 26555892 TI - Testing Local Adaptation in a Natural Great Tit-Malaria System: An Experimental Approach. AB - Finding out whether Plasmodium spp. are coevolving with their vertebrate hosts is of both theoretical and applied interest and can influence our understanding of the effects and dynamics of malaria infection. In this study, we tested for local adaptation as a signature of coevolution between malaria blood parasites, Plasmodium spp. and its host, the great tit, Parus major. We conducted a reciprocal transplant experiment of birds in the field, where we exposed birds from two populations to Plasmodium parasites. This experimental set-up also provided a unique opportunity to study the natural history of malaria infection in the wild and to assess the effects of primary malaria infection on juvenile birds. We present three main findings: i) there was no support for local adaptation; ii) there was a male-biased infection rate; iii) infection occurred towards the end of the summer and differed between sites. There were also site specific effects of malaria infection on the hosts. Taken together, we present one of the few experimental studies of parasite-host local adaptation in a natural malaria system, and our results shed light on the effects of avian malaria infection in the wild. PMID- 26555893 TI - A new look at oxide formation at the copper/electrolyte interface by in situ spectroscopies. AB - The widely used engineering material copper is a prototype of an electrochemically passive metal. In this work, the passive films on evaporated copper in 0.1 M NaOH are investigated in situ and operando by spectroscopic ellipsometry and Raman spectroscopy, both conducted during oxidation in potentiostatic step experiments. Oxide growth is initiated by jumping from a potential at which the surface is oxide-free to -0.1 V vs. Ag|AgCl|3 M KCl (+0.11 V vs. standard hydrogen electrode, SHE). At subsequent electrode potential jumps, no corresponding jumps in the thickness are observed; instead, oxide growth proceeds steadily. Above +0.3 V vs. Ag|AgCl|3 M KCl (+0.51 V vs. SHE), the oxide layer thickness remains constant at ~7 nm. Raman spectra show a peak at 530 cm( 1), which agrees with the dominant peak in spectra of copper mixed oxide, Cu4O3 (Cu2(I)Cu2(II)O3). Crystalline Cu4O3 nucleates from a precursor state showing strong photoluminescence (PL), which hints at the involvement of Cu2O. Overall, the PL spectra of the growing oxide and absorption spectra indicate the presence of Cu2O in the thin films. Absorption spectra cannot be understood as a superposition of the spectra from different well-described copper oxides, which points to defect-rich oxides that show rather different spectra. Raman spectra also point to an involvement of both crystalline and amorphous oxides that coexist. The results show that the passive layers on copper are more complex than the duplex layers described in the literature; they do contain an oxide with a mixed valency of copper. PMID- 26555894 TI - miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth. AB - The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3' untranslated region (UTR) analysis upon miR-17 19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3' UTR shortening at different stages of tumorigenesis. PMID- 26555895 TI - A Unifying Organ Model of Pancreatic Insulin Secretion. AB - The secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic beta cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 10 minutes) and low-frequency oscillations (period approx. 1.5 hours). Furthermore, characteristic insulin secretory response to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation; substantial insulin peaks following minimal glucose administration; progressively strengthened insulin secretion response after repeated administration of the same amount of glucose; insulin and glucose characteristic curves after Intra-Venous administration of glucose boli in healthy and pre-diabetic subjects as well as in Type 2 Diabetes Mellitus. Previous modeling of beta-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Starting with the seminal work of Grodsky it was hypothesized that the population of pancreatic beta-cells, possibly functionally aggregated in islets of Langerhans, could be viewed as a set of independent, similar, but not identical controllers (firing units) with distributed functional parameters. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters. The model's success in reproducing a diverse array of experiments implies that, in order to understand the macroscopic behaviour of the endocrine pancreas in regulating glycemia, there is no need to hypothesize intrapancreatic pacemakers, influences between different islets of Langerhans, glycolitic-induced oscillations or beta cell sensitivity to the rate of change of glycemia. PMID- 26555897 TI - Predictors of Fatigue in Rheumatoid Arthritis Patients in Remission or in a Low Disease Activity State. AB - OBJECTIVE: Fatigue is a frequently occurring symptom in patients with rheumatoid arthritis (RA). Our aims were to assess the level of reported fatigue in RA patients who had achieved remission or low disease activity after 6 months of treatment with disease-modifying antirheumatic drugs (DMARDs), and to explore associations between fatigue and demographics, disease activity, and other patient-reported outcomes in this patient group. METHODS: A total of 2,193 RA patients (ages >=18 years) starting either methotrexate (MTX) monotherapy or a tumor necrosis factor inhibitor in combination with MTX were retrieved from the Norwegian Disease-Modifying Antirheumatic Drugs Register (NOR-DMARD). At the 6 month followup, 699 patients (31.9%) were in remission or in a low disease activity state. Bivariate and multivariate linear regression analyses were conducted, with the fatigue visual analog scale (VAS) at 6 months as the dependent variable. Age, sex, disease duration, treatment group, erythrocyte sedimentation rate (ESR), the swollen and tender joint count in 28 joints, the pain VAS score, and disability at baseline and at 6 months were tested as predictors of fatigue at 6 months. RESULTS: At 6 months, the median (25th, 75th percentile) level of fatigue was 20.0 mm (6.0, 43.0), and a fatigue VAS score of >=40 mm was reported by 27.9% of patients. In the multivariate analysis, lower ESR and higher pain at baseline were statistically significant predictors of higher levels of fatigue (P < 0.001). In the multivariate cross-sectional analysis at 6 months, younger age and greater pain were significantly associated with higher levels of fatigue (P < 0.001). CONCLUSION: Pain levels at baseline and at 6 months were associated with a higher level of fatigue. Patients in remission or in a low disease activity state may need nonpharmacologic interventions to manage their pain and fatigue. PMID- 26555896 TI - Chronic Diseases in North-West Tanzania and Southern Uganda. Public Perceptions of Terminologies, Aetiologies, Symptoms and Preferred Management. AB - BACKGROUND: Research has shown that health system utilization is low for chronic diseases (CDs) other than HIV. We describe the knowledge and perceptions of CDs identified from rural and urban communities in north-west Tanzania and southern Uganda. METHODS: Data were collected through a quantitative population survey, a quantitative health facility survey and focus group discussions (FGDs) and in depth interviews (IDIs) in subgroups of population survey participants. The main focus of this paper is the findings from the FGDs and IDIs. RESULTS: We conducted 24 FGDs, involving approximately 180 adult participants and IDIs with 116 participants (>=18 years). CDs studied included: asthma/chronic obstructive lung disease (COPD), diabetes, epilepsy, hypertension, cardiac failure and HIV- related disease. The understanding of most chronic conditions involved a combination of biomedical information, gleaned from health facility visits, local people who had suffered from a complaint or knew others who had and beliefs drawn from information shared in the community. The biomedical contribution shows some understanding of the aetiology of a condition and the management of that condition. However, local beliefs for certain conditions (such as epilepsy) suggest that biomedical treatment may be futile and therefore work counter to biomedical prescriptions for management. CONCLUSION: Current perceptions of selected CDs may represent a barrier that prevents people from adopting efficacious health and treatment seeking behaviours. Interventions to improve this situation must include efforts to improve the quality of existing health services, so that people can access relevant, reliable and trustworthy services. PMID- 26555898 TI - Exclusion of solar UV radiation improves photosynthetic performance and yield of wheat varieties. AB - Field studies were conducted to determine the potential for alterations in photosynthetic performance and grain yield of four wheat (Triticum aestivum) varieties of India- Vidisha, Purna, Swarna and Naveen Chandausi by ambient ultraviolet radiation (UV). The plants were grown in specially designed UV exclusion chambers, wrapped with filters that excluded UV-B (<315 nm), UV-A/B (<400 nm) or transmitted ambient UV or lacked filters. The results indicated that solar UV exclusion increased the leaf mass per area ratio, leaf weight ratio and chlorophylls per unit area of flag leaves in all the four varieties of wheat. Polyphasic chlorophyll a fluorescence transients from the flag leaves of UV excluded wheat plants gave a higher fluorescence yield. Exclusion of solar UV significantly enhanced photosynthetic performance as a consequence of increased efficiency of PS II, performance index (PIABS) and rate of photosynthesis in the flag leaves of wheat varieties along with a remarkable increase in carbonic anhydrase, Rubisco and nitrate reductase activities. This additional fixation of carbon and nitrogen by exclusion of UV was channelized towards the improvement in grain yield of wheat varieties as there was a decrease in the UV-B absorbing substances and an increase in soluble protein content in flag leaves of all the four varieties of wheat. The magnitude of response for UV exclusion for all the measured parameters was higher in two varieties of wheat Vidisha and Purna as compared to Swarna and Naveen Chandausi. Cumulative stress response index (CSRI) for each variety was developed from the cumulative sum of physiological and yield parameters such as leaf mass area ratio of flag leaf, total chlorophyll content, performance index at absorption basis, rate of photosynthesis and grain yield. All the varieties had a negative CSRI, demonstrating a negative impact of ambient UV radiation. Naveen Chandausi and Swarna are less sensitive to ambient UV radiation; Vidisha is more sensitive to both UV-A and UV-B and Purna is more sensitive to ambient UV-B radiation. PMID- 26555899 TI - Mechanistic study of programmed cell death of root border cells of cucumber (Cucumber sativus L.) induced by copper. AB - Programmed cell death (PCD) in root border cells (RBCs) induced by Copper (Cu) has been little studied. This study explored whether Cu induced PCD in RBCs of cucumber or not and investigated the possible mechanisms. The results showed that the percentage of apoptotic and necrotic RBCs increased with increasing concentration of Cu treatment. A quick burst of ROS in RBCs was detected, while mitochondrial membrane potential (DeltaPsim) decreased sharply with Cu treatment. Caspase-3 like protease activity showed a tendency of increase with Cu treatment. The potential of Cu to induce PCD in RBCs of cucumber was first proved. Our results showed that ROS generation and mitochondrial membrane potential loss played important roles in Cu-induced caspase-3-like activation and PCD in RBCs of cucumber, which provided new insight into the signaling cascades that modulate Cu phytotoxicity mechanism. PMID- 26555900 TI - Multiple abiotic stress tolerance of the transformants yeast cells and the transgenic Arabidopsis plants expressing a novel durum wheat catalase. AB - Catalases are reactive oxygen species scavenging enzymes involved in response to abiotic and biotic stresses. In this study, we described the isolation and functional characterization of a novel catalase from durum wheat, designed TdCAT1. Molecular Phylogeny analyses showed that wheat TdCAT1 exhibited high amino acids sequence identity to other plant catalases. Sequence homology analysis showed that TdCAT1 protein contained the putative calmodulin binding domain and a putative conserved internal peroxisomal targeting signal PTS1 motif around its C-terminus. Predicted three-dimensional structural model revealed the presence of four putative distinct structural regions which are the N-terminal arm, the beta-barrel, the wrapping and the alpha-helical domains. TdCAT1 protein had the heme pocket that was composed by five essential residues. TdCAT1 gene expression analysis showed that this gene was induced by various abiotic stresses in durum wheat. The expression of TdCAT1 in yeast cells and Arabidopsis plants conferred tolerance to several abiotic stresses. Compared with the non transformed plants, the transgenic lines maintained their growth and accumulated more proline under stress treatments. Furthermore, the amount of H2O2 was lower in transgenic lines, which was due to the high CAT and POD activities. Taken together, these data provide the evidence for the involvement of durum wheat catalase TdCAT1 in tolerance to multiple abiotic stresses in crop plants. PMID- 26555901 TI - Isolation and expression analysis of 18 CsbZIP genes implicated in abiotic stress responses in the tea plant (Camellia sinensis). AB - Basic leucine zipper (bZIP) transcription factors (TFs) play essential roles in regulating stress processes in plants. Despite the economic importance of this woody crop, there is little information about bZIP TFs in tea plants. In this study, 18 bZIP genes were isolated from the tea plant (Camellia sinensis) and named sequentially from CsbZIP1 to CsbZIP18. According to the phylogenetic classification as in Arabidopsis, the CsbZIP genes spanned ten subgroups (Group A, B, C, D, E, F, H, I, S and K) of bZIP TFs. When analyzed for organ specific expression, all CsbZIP genes were found to be ubiquitously expressed in roots, stems, leaves and flowers. Expression analysis of CsbZIP genes in response to four abiotic stresses showed that in leaves, 9, 9, 15 and 11 CsbZIPs have 2-fold greater variation in transcript abundance under cold, exogenous ABA, high salinity and dehydration conditions, respectively. In roots, 5, 12, 14 and 11 CsbZIPs were differentially expressed under conditions of cold, exogenous ABA, high salinity and dehydration stresses. Moreover, CsbZIP genes in Groups F, H, S and K exhibited several folds up-and/or down-regulation against the above four stresses. Notably, CsbZIP18 of group K showed significant up-regulation in response to these same stresses, suggesting a vital functional role in stress response. Together, these findings increase our knowledge of bZIP TFs in the tea plant and suggest the significance of CsbZIP genes in plant abiotic responses. PMID- 26555903 TI - The relation between flow mediated dilation and atrial fibrillation. PMID- 26555904 TI - Response to "Pacemaker indication in first-degree AV block patients: Factors beyond the PR interval/HR slope". PMID- 26555902 TI - Knockdown of Inner Arm Protein IC138 in Trypanosoma brucei Causes Defective Motility and Flagellar Detachment. AB - Motility in the protozoan parasite Trypanosoma brucei is conferred by a single flagellum, attached alongside the cell, which moves the cell forward using a beat that is generated from tip-to-base. We are interested in characterizing components that regulate flagellar beating, in this study we extend the characterization of TbIC138, the ortholog of a dynein intermediate chain that regulates axonemal inner arm dynein f/I1. TbIC138 was tagged In situ-and shown to fractionate with the inner arm components of the flagellum. RNAi knockdown of TbIC138 resulted in significantly reduced protein levels, mild growth defect and significant motility defects. These cells tended to cluster, exhibited slow and abnormal motility and some cells had partially or fully detached flagella. Slight but significant increases were observed in the incidence of mis-localized or missing kinetoplasts. To document development of the TbIC138 knockdown phenotype over time, we performed a detailed analysis of flagellar detachment and motility changes over 108 hours following induction of RNAi. Abnormal motility, such as slow twitching or irregular beating, was observed early, and became progressively more severe such that by 72 hours-post-induction, approximately 80% of the cells were immotile. Progressively more cells exhibited flagellar detachment over time, but this phenotype was not as prevalent as immotility, affecting less than 60% of the population. Detached flagella had abnormal beating, but abnormal beating was also observed in cells with no flagellar detachment, suggesting that TbIC138 has a direct, or primary, effect on the flagellar beat, whereas detachment is a secondary phenotype of TbIC138 knockdown. Our results are consistent with the role of TbIC138 as a regulator of motility, and has a phenotype amenable to more extensive structure-function analyses to further elucidate its role in the control of flagellar beat in T. brucei. PMID- 26555905 TI - There is a link between carotid intima media thickness and coronary artery disease: It might be inflammation. PMID- 26555906 TI - Preferential nitrite inhibition of the mitochondrial F1FO-ATPase activities when activated by Ca(2+) in replacement of the natural cofactor Mg(2+). AB - BACKGROUND: The mitochondrial F1FO-ATP synthase has not only the known life function in building most cellular ATP, but also, as recently hinted, an amazing involvement in cell death. Accordingly, the two-faced enzyme complex, which catalyzes both ATP synthesis and ATP hydrolysis, has been involved in the mitochondrial permeability transition, the master player in apoptosis and necrosis. Nitrite, a cellular nitric oxide reservoir, has a recognized role in cardiovascular protection, through still unclear mechanisms. METHODS: In swine heart mitochondria the effect of nitrite on the F1FO-ATPase activity activated by Ca(2+), henceforth defined as Ca-ATPase(s), or by the natural cofactor Mg(2+), was investigated by evaluating ATP hydrolysis under different assay conditions. RESULTS: Ca(2+) is far less efficient than the natural cofactor Mg(2+) in the ATPase activation. However, when activated by Ca(2+) the ATPase activity is especially responsive to nitrite, which acts as uncompetitive inhibitor and up to 2 mM inhibits the Ca2+-activated-ATPase(s), probably by promoting dytirosine formation on the enzyme proteins, leaving the Mg-ATPase(s) unaffected. Most likely these ATPases refer to the same F1FO complex, even if coexistent ATPases may overlap. CONCLUSIONS: The preferential inhibition by nitrite of the Ca ATPase(s), due to post-translational tyrosine modifications, may prevent the calcium-dependent functionality of the mitochondrial F1FO complex and related events. GENERAL SIGNIFICANCE: In mitochondria the preferential inhibition of the Ca-ATPase activity/ies by nitrite concentrations which do not affect the coexistent Mg-ATPase(s) may quench the negative events linked to the calcium dependent functioning mode of the F1FO complex under pathological conditions. PMID- 26555907 TI - [Early Postoperative Outcomes and Evaluation of Hemodynamics after Mitral Valve Replacement with Epic Mitral Bioprosthesis]. AB - BACKGROUND: In Guideline for Surgical and Interventional Treatment of Valvular Heart Disease, revised by Japanese Circulation Society in 2012, mitral valve replacement (MVR) with bioprosthesis is class II b recommendation for patients aged 70 years or older who have no risk factors for thromboembolism. The aim of this study was to evaluate the early postoperative surgical outcomes and the hemodynamic performance with the Epic mitral bioprosthesis. METHODS: Twenty-six consecutive patients underwent MVR with Epic mitral bioprostesis at Tohoku University Hospital between April 2011 and July 2014. Twenty-five cases of 26 were evaluated their hemodynamics at discharge, and of which 19 cases of 26 were evaluated at the outpatient clinic during follow-up period. RESULTS: There was 1 hospital death. Long-term mortality or reoperation for any valve abnormality was not observed in the median follow-up of 23.9 +/- 11.3 months. Hemodynamic date at discharge obtained by transthoracic echocardiography included mean hemodynamics of mitral valve bioprosthesis as below. Effective orifice area (EOA):2.44 +/- 0.62 cm2, peak mitral pressure gradient (pMPG):15.8 +/- 5.3 mmHg, mean mitral pressure gradient(mMPG):7.2 +/- 2.4 mmHg. Hemodynamic parameters at follow-up were found to be stable as EOA:2.25 +/- 0.64 cm2, pMPG:17.3 +/- 5.7 mmHg, mMPG:6.2 +/- 2.3 mmHg, respectively. CONCLUSION: We have attempted to elucidate our preliminary postoperative outcomes and hemodynamics after MVR with Epic mitral bioprosthesis. These in vivo hemodynamic data can serves a clinical reference. PMID- 26555908 TI - [Postoperative Superior Mesenteric Artery and Cerebral Infarction Possibly due to the Thrombus at the Left Superior Pulmonary Vein Stump]. AB - Pulmonary vein stump thrombus (PVST) was thought to be a rare complication after lung resection. Several cases of embolism due to PVST were reported previously. However, in recent paper, PVST was reported to be found in 13.5% of patients after left upper lobectomy ( LUL). We experienced a case of PVST that induced acute embolism of the superior mesenteric artery at 2 weeks after LUL. After discontinuation of anticoagulation therapy, development of PVST was confirmed by computed tomography scan at 12 months after LUL resulting in cerebral infarction. PMID- 26555909 TI - [Additional Lobectomy after Pulmonary Excision for Non-invasive Lung Adenocarcinoma due to Malignant Positive Cytology at the Residual Lube]. AB - A 67-year-old male was pointed out a pure ground grass opacity sized 1.7 cm in computed tomography (CT), which reminded unchanged size in CT findings for 18 months. This region was removed using pulmonary wedge resection with margin length of 0.5 cm and clustered pulmonary adenocarcinoma cells were revealed by cytological examination at the margin of the residual lung, thus additional left upper lobectomy was performed later. PMID- 26555910 TI - [In situ Replacement with Bovine Pericardial Roll Graft for Infected Aneurysm of the Thoracoabdominal Aorta]. AB - A 63-year-old man presented to a nearby doctor with fever and lumbago. Enhanced computed tomography showed a thoracoabdominal aortic aneurysm and enhancement of soft tissue around the aneurysm. He was diagnosed with an infected thoracoabdominal aortic aneurysm and given antibiotics. After 2 weeks, the infection was controlled and he underwent in situ replacement with a bovine pericardial roll graft. A week after the operation, the inflammatory reaction was increased, but the bovine pericardial roll graft was not infected. This suggests that a bovine pericardial roll graft is a suitable material for use in patients with bacterial infections. PMID- 26555911 TI - [Mitral Valve Plasty in a Patient with Situs Inversus Totalis; Usefulness of Retrograde Cardioprotective Beating Test]. AB - We report the usefulness of retrograde cardioprotective(RC)-beating test as a method to evaluate mitral valve plasty (MVP). MVP has been established as an effective procedure for mitral regurgitation, but nevertheless, a problem remains as to how to reduce postoperative residual regurgitation. In order to solve this problem, it is crucial to image the 3 dimensional structures of the mitral valve and its systolic condition. However, it is quite difficult especially in cases of situs inversus totalis (SIT). RC-beating test gives a clear view of the mitral valve and precisely evaluates the performance of MVP, which is particulary helpful in SIT patients. It also shows where to revise in cases of residual regurgitation. PMID- 26555912 TI - [Mitral Valvuloplasty of Infective Endocarditis During Pregnancy]. AB - This report describes a case in which we treated a patient who developed infective endocarditis in the mitral valve at 28 weeks' gestation. The condition was resolved by performing mitral valvuloplasty 2 days after an emergency cesarean section. Although the patient was in a relatively stable period at 32 weeks' gestation, the mother had an extremely high risk of embolism;thus, emergency surgery was required. We believe that an accurate diagnosis in a timely manner and a valvuloplasty shortly after cesarean section saved the life of the mother and child. PMID- 26555913 TI - [Tiny Size Lung Cancer which was not Pathologically Diagnosed before Hilar and Mediastinal Dissection]. AB - A 63-year-old man was found to have abnormally high carcinoembryonic antigen levels in a health examination. Computed tomography scan revealed lymphadenopathy at the right hilum of lung and right upper mediastinum. Malignancy was suggested by endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)for lymph node. Lymph node metastases of lung cancer was suspected, but primary site was unidentified. In order to perform complete hilar dissection, right upper lobectomy was done with systematic mediastinal dissection. Pathological diagnosis was adenocarcinoma of 3 * 3 mm in size in the fibrous scar of the right upper lobe. Immunostaining revealed thyroid transcription factor-1(TTF-1) [+]and paired box-8(PAX-8) [-] indicating the tumor to be a primary lung cancer. PMID- 26555914 TI - [Alpha Fetoprotein-producing Lung Adenocarcinoma]. AB - We report a case of alpha fetoprotein (AFP) -producing lung adenocarcinoma. A 53 year-old man was referred to our hospital due to right pneumothorax. Computed tomography showed right moderate pneumothorax, a solid tumor in the upper lobe (S3) and mediastinal lymph node swelling. The serum AFP level was as high as 223.0 ng/ml. Frozen examination revealed a low-differentiated adenocarcinoma. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as AFP-producing lung adenocarcinoma. PMID- 26555915 TI - [Pulmonary Metastasis from a Phyllodes Tumor of the Breast Developing Sixteen Years after Initial Surgery]. AB - We report a case of solitary pulmonary metastasis from a phyllodes tumor of the breast appearing 16 years after initial surgery. The patient was a 56-year-old woman who had undergone surgical extirpation of a left breast tumor diagnosed as phyllodes tumor (borderline malignancy) in 1998, and a right breast tumor diagnosed as fibromatosis in 2000. Sixteen years after the initial operation, she consulted our hospital because of a chest X-ray abnormality detected at a screening examination. Chest computed tomography revealed a well defined nodular shadow in the left upper lobe of the lung. Surgery was done since primary lung cancer was suspected. However, pathological diagnosis was a pulmonary metastasis from the phyllodes tumor of the left breast. Right breast tumor was also diagnosed as a metastasis from the left breast tumor by histopathological re evaluation. PMID- 26555916 TI - [Pulmonary Lipomatous Hamartoma Suspected to be an Endobronchial Lipoma]. AB - We report a rare case of pulmonary lipomatous hamartoma. A 61-year-old male was referred to our hospital due to abnormal mass densities on a chest radiograph. Thoracic computed tomography (CT) revealed a tumor with a maximum diameter of 42 mm. Bronchoscopic examination indicated the presence of a tumor at the orifice of the lateral segmental bronchus which was obstructed by the tumor. Endobronchial lipoma, was suspected by transbronchial biopsy, and we carried out a left upper lobectomy to prevent obstructive pneumonia. The pathological diagnosis was lipomatous hamartoma. PMID- 26555917 TI - [Emergency Redo Off-pump Coronary Artery Bypass Surgery after 22 Years in an Elderly; Report of a Case]. AB - An 84-year-old male presented to our hospital with recurrent angina. He had undergone coronary artery bypass with a saphenous vein graft to the left anterior descending branch (LAD) 22 years before. Coronary angiography showed occulusion of the proximal LAD and significant stenosis of the saphenous vein graft. An emergency redo operation was conducted using the left internal thoracic artery for LAD revascularization. The postoperative course was uneventful and the patient was discharged in a week. Emergency redo coronary bypass surgery can be indicated even in octogenarians who are resistant to medical treatment. PMID- 26555918 TI - [Discrete Subaortic Stenosis in an Adult; Report of a Case]. AB - Discrete subaortic stenosis (DSS) is a well-described cause of isolated left ventricular outflow tract obstruction( LVOTO) in children. But prevalence, rate of progression and postoperative data in adults are limited. We report a case of a 30-year-old woman, who was referred to our institution because of chest pain and loss of consciousness. Echocardiography revealed DSS with LVOTO (peak gradient 81 mmHg) and mild aortic regurgitation. Increased age at the time of diagnosis, female sex and preoperative left ventricular outflow tract(LVOT) gradient >=80 mmHg were thought to be predictors for reoperation, therefore the obstructing membrane was circumferentially excised and concomitant localized myectomy of the ventricular septum was performed to achieve complete relief of the LVOT obstruction. Her postoperative course was uneventful, and she was discharged on the 5th postoperative day. PMID- 26555919 TI - [Papillary Muscle Rupture after Repair of Ischemic Left Ventricular Free Wall Rupture; Report of a Case]. AB - A 67-year-old man experienced acute inferior myocardial infarction. Echocardiography and computed tomography showed massive pericardial effusion. He underwent emergency operation for ischemic ventricular free wall rupture. During the operation, an oozing type rupture was found on the inferior wall and the bleeding was completely controlled by applying fibrin glue sheets. On the 5th day after the operation, ventricular tachycardia appeared with hemodynamic deterioration. Echocardiography showed a ruptured posteromedial papillary muscle with massive mitral regurgitation. Intra-aortic balloon pumping was introduced and emergency repair operation was performed. The mitral valve was replaced with a bioprosthetic valve. The postoperative course was uneventful. PMID- 26555920 TI - [Unroofed Coronary Sinus in an Adult; Report of a Case]. AB - Unroofed coronary sinus( UCS) is a rare cardiac anomaly and the most uncommon type of atrial septal defect. It is rarely diagnosed by only echocardiography prior to surgery. We herein report a case of UCS (partially unroofed terminal portion) without persistent left superior vena cava that was precisely diagnosed by cardiac multi-detector low computed tomography (MDCT). A 50-year-old asymptomatic man was admitted for cardiac evaluation. A transesophageal echocardiography showed a left to right shunt at the atrial level. MDCT clearly showed a defect in the coronary sinus and lower part of the interatrial septum. At the time of surgery, the defect was closed using a Gore-Tex patch, such that the coronary sinus drained entirely into the left atrium. The postoperative course was uneventful. Cardiac MDCT provides accurate anatomic details about defects as well as the associated anomalies of the heart and pulmonary vasculature. PMID- 26555921 TI - [Cardiac Amyloidosis Diagnosed Following Mitral Valve Repair; Report of a Case]. AB - We present a case of a 60-year-old female who underwent elective mitral valve repair for mitral valve regurgitation. Intra-aortic balloon pumping was necessary to wean her from cardiopulmonary bypass, and a sudden cardiac arrest happened on postoperative day 17. Due to such unexpected postoperative course, a right ventricular biopsy was done, and she was diagnosed with light chain amyloidosis (AL) type cardiac amyloidosis. Despite long percutaneous cardiopulmonary bypass support, she never recovered from severe heart failure. Cardiac surgeons should be aware of this fatal disease, and preoperative screening with various tests is required. PMID- 26555922 TI - [Spontaneous Pneumothorax During Pregnancy Successfully Managed with a Thoracic Vent before Surgical Therapy; Report of a Case]. AB - A 34-year-old pregnant woman presented to our department at 31 weeks of gestation after being diagnosed as spontaneous pneumothorax based on chest X-ray findings. We inserted a Thoracic Vent( TV), and she was followed as an outpatient. However, since pneumothorax recurred twice after the TV was removed, she was finally admitted to the Department of Obstetrics because threatened premature delivery was suspected. The collapsed lung did not re-expand, and the surgery for pneumothorax was done before childbirth. After thoracic surgery, she safely gave birth to a girl at 40 weeks of gestation. Outpatient therapy for spontaneous pneumothorax with TV is concerned to be a useful treatment even for pregnant women. PMID- 26555923 TI - [Successful Treatment of Empyema with Bronchial Fistulas by Filling under Thoracoscopic Observation; Report of a Case]. AB - Empyema with fistula usually resists conservative treatment such as thoracic cavity drainage and administration of antibacterial agents, thus it often requires surgeries such as fenestration, omental/muscle filling, and thoracoplasty. However, due to advanced age and poor condition, conducting invasive surgeries is often difficult in elderly patients. We report a case with the improvement of empyema by bronchial filling with endobronchial Watanabe spigot (EWS) under thoracoscopic observation for an 89-year-old patient who had developed chronic empyema with a bronchial fistulas. After filling EWS, air leakage from bronchial fistula disappeared and the patient could discharged from the hospital successfully. PMID- 26555924 TI - A case of unilateral coronal synostosis from Medieval Hungary (9th century A.D.). AB - A unique single suture craniosynostosis case from the 9(th) century is presented in this paper. Although craniosynostosis is a fairly common pediatric anomaly nowadays, its occurrence in archaeological collections is an uncommon precedent. Since the diagnosis and treatment of premature cranial suture closure usually happens at an early age, evaluation of the whole developmental process is a rare opportunity. The right-sided coronal suture synostosis of this 30-35 years old woman gives an interesting opportunity to observe the effect of this phenomenon in adulthood. Only slight distortion of the viscerocranium and no bony signs of elevated intracranial pressure can be seen on the skull. The women suffered remarkable bending of the whole face and cranial base of the midsagittal plane. Besides the aesthetic disorder, the condition might have contributed to a chronic headache and visual disturbances. The lack of any other typical symptom suggests the diagnosis of isolated craniosynostosis or a milder type of syndromic craniosynostosis, the possibility of an underlying causative mutation cannot be ruled out. PMID- 26555926 TI - Engineered 3D Silk-collagen-based Model of Polarized Neural Tissue. AB - Despite huge efforts to decipher the anatomy, composition and function of the brain, it remains the least understood organ of the human body. To gain a deeper comprehension of the neural system scientists aim to simplistically reconstruct the tissue by assembling it in vitro from basic building blocks using a tissue engineering approach. Our group developed a tissue-engineered silk and collagen based 3D brain-like model resembling the white and gray matter of the cortex. The model consists of silk porous sponge, which is pre-seeded with rat brain-derived neurons, immersed in soft collagen matrix. Polarized neuronal outgrowth and network formation is observed with separate axonal and cell body localization. This compartmental architecture allows for the unique development of niches mimicking native neural tissue, thus enabling research on neuronal network assembly, axonal guidance, cell-cell and cell-matrix interactions and electrical functions. PMID- 26555925 TI - Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor. AB - The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8-24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor. PMID- 26555927 TI - Sucralose as co-crystal co-former for hydrochlorothiazide: development of oral disintegrating tablets. AB - Development of oral disintegrating tablets requires enhancement of drug dissolution and selection of sweetener. Co-crystallization of drugs with inert co former is an emerging technique for enhancing dissolution rate. The benefit of this technique will become even greater if one of the sweeteners can act as co crystal co-former to enhance dissolution and mask the taste. Accordingly, the objective of this work was to investigate the efficacy of sucralose as a potential co-crystal co-former for enhancing the dissolution rate of hydrochlorothiazide. This was extended to prepare oral disintegrating tablets. Co crystallization was achieved after dissolving hydrochlorothiazide with increasing molar ratios of sucralose in the least amount of acetone. The co-crystallization products were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and powder X-ray diffraction. These measurements indicated that co-crystallization process started at a drug sucralose molar ratio of 1:1 and completed at 1:2. The developed co-crystals exhibited faster drug dissolution compared with the control, with co-crystal containing the drug with sucralose at 1:2 molar ratio being optimum. The later was used to prepare fast disintegrating tablets. These tablets had acceptable physical characteristics and showed fast disintegration with subsequent rapid dissolution. The study introduced sucralose as co-crystal co-former for enhanced dissolution and masking the taste. PMID- 26555928 TI - Polynuclear platinum phosphanido/phosphinito complexes: formation of P-O and P-O P bonds through reductive coupling processes. AB - A mixture of the asymmetric complexes of formula [(RF)2Pt(MU-Ph2PO)(MU-PPh2)Pt(MU PPh2)2Pt(solv)(solv')] [(1-(solv)(solv')] (solv, solv' = acetone, H2O, CH3CN) has been prepared by reaction of [(RF)2Pt(II)(MU-PPh2)2Pt(II)(MU PPh2)2Pt(II)(NCCH3)2] with AgClO4 in CH3CN/acetone. The lability of the Pt solvent bonds allows the displacement of the coordinated solvent molecules by dppm or Cl(-) and the isolation of the tri- or hexanuclear phosphanido/phosphinito Pt(ii) complexes [(C6F5)2Pt(MU-PPh2)(MU-PPh2O)Pt(MU PPh2)2Pt(dppm)] (2) or [NBu4]2[(C6F5)2Pt(MU-PPh2)(MU-PPh2O)Pt(MU-PPh2)2Pt(MU Cl)2Pt(MU-PPh2)2Pt(MU-PPh2)(MU-PPh2O)Pt(C6F5)2] (as a mixture of the two possible isomers 4a and 4b). Complex 2 reacts with AgClO4 to form the tetranuclear derivative [(C6F5)2Pt(MU-PPh2)(MU-PPh2O)Pt(MU-PPh2)2Pt(dppm)Ag(OClO3)] (3), which displays two Pt-Ag donor-acceptor bonds. The mixture of the hexanuclear isomers 4a-4b reacts with Tl(acac) producing the acetylacetonato complex [NBu4][(C6F5)2Pt(MU-PPh2)(MU-PPh2O)Pt(MU-PPh2)2Pt(acac)] (5) which, upon reaction with HCl, yields back the mixture of 4a-4b. The reaction of 4a-4b with PPh3 produces [NBu4][(C6F5)2Pt(MU-PPh2)(MU-PPh2O)Pt(MU-PPh2)2Pt(Cl)(PPh3)] (6) as a mixture of isomers with the chloro ligand located syn (6a) or anti (6b) to the PPh2O(-) group. Either the reaction of 6 with AgClO4 or the treatment of 5 with HPPh3ClO4 results in the formation of the species [(C6F5)2Pt(II)(MU PPh2)2Pt(I)(MU-PPh2OPPh2)Pt(I)(PPh3)] (7) (44 VEC), which can be explained as the consequence of a PPh2O/PPh2 reductive coupling and a rearrangement of ligands in the molecule generating a Pt(ii),Pt(i),Pt(i) compound. All complexes were characterised in the solid state by XRD (only one of the isomers, in the cases of 4 and 6) and in solution by NMR spectroscopy. PMID- 26555929 TI - Influence of the Compatible Solute Ectoine on the Local Water Structure: Implications for the Binding of the Protein G5P to DNA. AB - Microorganisms accumulate molar concentrations of compatible solutes like ectoine to prevent proteins from denaturation. Direct structural or spectroscopic information on the mechanism and about the hydration shell around ectoine are scarce. We combined surface plasmon resonance (SPR), confocal Raman spectroscopy, molecular dynamics simulations, and density functional theory (DFT) calculations to study the local hydration shell around ectoine and its influence on the binding of a gene-5-protein (G5P) to a single-stranded DNA (dT25). Due to the very high hygroscopicity of ectoine, it was possible to analyze the highly stable hydration shell by confocal Raman spectroscopy. Corresponding molecular dynamics simulation results revealed a significant change of the water dielectric constant in the presence of a high molar ectoine concentration as compared to pure water. The SPR data showed that the amount of protein bound to DNA decreases in the presence of ectoine, and hence, the protein-DNA dissociation constant increases in a concentration-dependent manner. Concomitantly, the Raman spectra in terms of the amide I region revealed large changes in the protein secondary structure. Our results indicate that ectoine strongly affects the molecular recognition between the protein and the oligonucleotide, which has important consequences for osmotic regulation mechanisms. PMID- 26555930 TI - Tet-on, or Tet-off, that is the question: Advanced conditional gene expression in Aspergillus. AB - In Aspergillus, controlled gene expression is often achieved using the reverse tetracycline-controlled transactivator (rtTA) dependent Tet-on system, whereby transcription is activated in a titratable manner by addition of the tetracycline derivative doxycycline. The complementary Tet-off system utilises the tetracycline-controlled transactivator (tTA) component to quantitatively reduce gene expression. In this study, we utilised a synthetic biological approach to engineer highly optimised Tet-off conditional expression systems in Aspergillus niger and Aspergillus fumigatus. Steps for delivery of these tools include utilising codon optimised cassette components, testing several promoters for improved genetic stability and validating two modified luciferase reporters for highly accurate measurements of gene expression. The Tet-off cassettes developed in this study enable facile and quantitative functional analysis, as validated by Tet-off analysis of genes involved in chitin synthesis and cell wall polarity in A. niger, and para-aminobenzoic acid synthesis in A. fumigatus. We also used a racA(G18V) dominant allele to demonstrate that Tet-off in A. niger enables gene over-expression and downregulation in a single isolate. Additionally, we used the improved luciferase reporters to show that the Tet-off cassette in A. niger enables quantification of gene oscillations. In order to demonstrate that synthetic biological approaches developed here are broadly applicable to engineering transcriptional circuits in filamentous fungi, we used our strategy for improving cassette stability by promoter replacement in the A. niger Tet-on system, which resulted in a modified Tet-on cassette with higher stability in recipient genomes. PMID- 26555932 TI - Electronic Cigarette Use Among Adults: United States, 2014. AB - The National Health Interview Survey (NHIS) first began collecting data about e cigarette use in 2014. The estimates presented in this report provide a foundation for understanding who is using e-cigarettes and for monitoring changes in e-cigarette use among U.S. adults over time. In 2014, men were more likely than women to have ever tried e-cigarettes but were not more likely to be current users. Younger adults were more likely than older adults to have tried e cigarettes and to currently use e-cigarettes. Both non-Hispanic AIAN and non Hispanic white adults were more likely than non-Hispanic black, non-Hispanic Asian, and Hispanic adults to have ever tried e-cigarettes and to be current e cigarette users. When examined in the context of conventional cigarette smoking, use of e-cigarettes was highest among current and recent former cigarette smokers, and among current smokers who had made a quit attempt in the past year. Although fewer than 4% of adults who had never smoked conventional cigarettes had ever tried an e-cigarette, nearly 1 in 10 never-smokers aged 18-24 had tried an e cigarette at least once. PMID- 26555931 TI - Efficient engineering of marker-free synthetic allotetraploids of Saccharomyces. AB - Saccharomyces interspecies hybrids are critical biocatalysts in the fermented beverage industry, including in the production of lager beers, Belgian ales, ciders, and cold-fermented wines. Current methods for making synthetic interspecies hybrids are cumbersome and/or require genome modifications. We have developed a simple, robust, and efficient method for generating allotetraploid strains of prototrophic Saccharomyces without sporulation or nuclear genome manipulation. S. cerevisiae*S. eubayanus, S. cerevisiae*S. kudriavzevii, and S. cerevisiae*S. uvarum designer hybrid strains were created as synthetic lager, Belgian, and cider strains, respectively. The ploidy and hybrid nature of the strains were confirmed using flow cytometry and PCR-RFLP analysis, respectively. This method provides an efficient means for producing novel synthetic hybrids for beverage and biofuel production, as well as for constructing tetraploids to be used for basic research in evolutionary genetics and genome stability. PMID- 26555933 TI - Analysis of 27 antibiotic residues in raw cow's milk and milk-based products- validation of Delvotest(r) T. AB - Delvotest(r) T was evaluated for its capability at detecting residues of 27 antibiotics in raw cow's milk and in some dairy ingredients (skimmed and full cream milk powders). The kit was used as a screening tool for the qualitative determination of antibiotics from different families in a single test. Results delivered by such a method are expressed as 'positive' or 'negative', referring to the claimed screening target concentration (STC). Validation was conducted according to the European Community Reference Laboratories' (CRLs) residues guidelines of 20 January 2010 and performed by two laboratories, one located in Europe and the other in Asia. Five criteria were evaluated including detection capability at STC, false-positive (FP) rate, false-negative (FN) rate, robustness and cross-reactivity using visual reading and Delvoscan(r). STCs were set at or below the corresponding maximum residue limit (MRL), as fixed by European Regulation EC No. 37/2010. Four antibiotics (nafcillin, oxytetracycline, tetracycline and rifaximin) out of 27 had a false-negative rate ranging from 1.7% to 4.9%; however, it was still compliant with the CRLs' requirements. Globally, Delvotest T can be recommended for the analysis of the surveyed antibiotics in raw cow's milk, skimmed and full-cream milk powders. Additional compounds were tested such as sulfamethazine, spiramycin and erythromycin; however, detection at the corresponding MRL was not achievable and these compounds were removed from the validation. Other drugs from the sulfonamide, aminoglycoside or macrolide families not detected by the test at the MRL were not evaluated in this study. Regarding the reliability of this rapid test to milk-based preparations, additional experiments should be performed on a larger range of compounds and samples to validate the Delvotest T in such matrices. PMID- 26555934 TI - Compliance with mechanical venous thromboproembolism prophylaxis after cesarean delivery. AB - OBJECTIVE: Universal perioperative mechanical thromboprophylaxis is recommended for patients undergoing cesarean delivery because of increased risk for venous thromboembolism (VTE) associated with this mode of delivery. While research supports clinical benefits from this approach, other specialties have demonstrated suboptimal compliance with prophylaxis device use. The objective of this study was to review patient compliance with sequential compression devices (SCDs). METHODS: This cross-sectional observational study utilized data from a prospective quality assurance analysis to evaluate demographic, medical and obstetrical factors associated with postoperative SCD compliance after cesarean delivery. Observations were performed before 7 a.m. on the first postoperative day, a time point when patients were unlikely to be fully ambulatory and would most benefit from device use. The reason for failure was documented in cases where the device was not being properly used. RESULTS: Two hundred and ninety three patients underwent cesarean delivery, had SCD compliance assessed and were included in the analysis. Twenty one percent of patients (n=60) were non compliant with SCD use. Reasons for noncompliance included patient discomfort, machine malfunction and incorrect device use. Patients who were non-compliant had similar risk factors for thromboembolism compared to women who were compliant. CONCLUSION: Although SCD's are effective in preventing thromboembolism, device use was suboptimal in this cohort of post-cesarean patients. These findings are similar to those from other fields. For institutions that rely primarily on mechanical thromboprophylaxis for obstetric patients, quality assurance and auditing of use may be necessary to ensure patients are receiving adequate prophylaxis. For post-cesarean patients with additional VTE risk factors, pharmacologic prophylaxis may be beneficial. PMID- 26555935 TI - DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association. AB - CONTEXT: DICER1 germline mutation carriers have an increased predisposition to cancer, such as pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT), and a high prevalence of multinodular goiter (MNG). Although differentiated thyroid carcinoma (DTC) has been reported in some DICER1 mutation carriers with PPB treated with chemotherapy, the association of DTC with DICER1 mutations is not well established. CASE DESCRIPTION: We report a family with DICER1 mutation and familial DTC without a history of chemotherapy. A 12-year-old female (patient A) and her 14-year-old sister (patient B) presented with MNG. Family history was notable for a maternal history of DTC and bilateral ovarian SLCT. Both sisters underwent total thyroidectomy. Pathological examination showed nodular hyperplasia and focal papillary thyroid carcinoma within hyperplastic nodules. Subsequently, patient A developed virilization secondary to a unilateral ovarian SLCT. During her evaluation, an incidental cystic nephroma was also found. Three other siblings had MNG on surveillance ultrasound examination; two had thyroidectomies, and one had two microscopic foci of papillary carcinoma. Patient A, her mother, and four affected siblings had a germline heterozygous pathogenic DICER1 mutation c.5441C>T in exon 25, resulting in an amino acid change from p.Ser1814Leu of DICER1. Somatic DICER1 RNase IIIb missense mutations were identified in thyroid nodules from three of the four siblings. CONCLUSIONS: This family provides novel insight into an emerging phenotype for DICER1 syndrome, with evidence that germline DICER1 mutations are associated with an increased risk of developing familial DTC, even in the absence of prior treatment with chemotherapy. PMID- 26555936 TI - Lipolytic Rate Associated With Intramyocardial Lipid in an HIV Cohort Without Increased Lipolysis. AB - CONTEXT: Individuals with HIV have an elevated risk for developing cardiovascular disease compared to controls, particularly in relationship to abnormal deposition of lipid within various body compartments. Dysregulation of lipolysis may contribute to abnormal deposition of lipid in non-adipose tissues such as the heart, leading to untoward health consequences. OBJECTIVE: To evaluate potential relationships between rates of whole-body lipolysis and intramyocardial lipid content in HIV-infected subjects compared to healthy controls. DESIGN: Cross sectional study. SETTING: National Institutes of Health Clinical Research Center in Bethesda, Maryland. PARTICIPANTS: Forty-six HIV-infected adults and 12 controls without known cardiovascular disease. MAIN OUTCOME MEASURE: Intramyocardial lipid content quantified by MRI and rates of lipolysis determined using stable isotope tracer techniques. RESULTS: We observed a significant positive correlation between the rate of appearance of glycerol and intramyocardial lipid overall (r = 0.323; P = .014) and among the HIV group separately (r = 0.361; P = .014). Multivariate regression analyses including HIV, lipid-lowering therapy, and diabetes identified both rate of appearance of glycerol and age as independent significant predictors of intramyocardial lipid (P = .01 and P = .03, respectively), but these were not significant with inclusion of visceral adipose in the analyses. CONCLUSIONS: To our knowledge, this study is among the first in humans to characterize the relationship between lipid deposition in the myocardium and direct measurement of whole-body fatty acid metabolism. Our current findings contribute to the growing understanding of factors that promote myocardial steatosis, such as visceral adiposity, and implicate lipolysis as a potential target for interventions to optimize myocardial health. PMID- 26555938 TI - Do psychosocial sleep interventions improve infant sleep or maternal mood in the postnatal period? A systematic review and meta-analysis of randomised controlled trials. AB - Sleep complaints are common amongst mothers of infants and insufficient, inefficient or fragmented sleep is associated with postnatal depression. The aim of this review is to determine whether psychosocial sleep-focused interventions offered in the perinatal period improve infant sleep or maternal mood. We searched PubMed, PsycInfo, EMBASE and CINAHL with no date restriction. We reviewed 1097 articles, resulting in nine papers (n = 1,656) that fit the eligibility criteria for inclusion in the analyses. The primary outcome was infant sleep, defined as maternal reports of infant nocturnal total sleep time and number of night-time wakes. The secondary outcome was maternal mood. The meta analysis indicated improvements in reported infant nocturnal total sleep time (Hedge's g = 0.204, p < 0.01). However, there was no evidence for reducing infant night wakes (Hedge's g = 0.103, p = 0.134). There was evidence of maternal mood improvements (Hedge's g = 0.152, p = 0.014), however, this could have been influenced by publication bias. Psychosocial sleep interventions appear to impact the amount of sleep that a mother reports her baby to have, although the infants continue to wake as frequently. More research is needed to confirm whether sleep related improvements can translate into improvements in maternal mood. PMID- 26555940 TI - Subpubic Arch Angle and Mode of Delivery in Low-Risk Nulliparous Women. AB - OBJECTIVE: To assess whether subpubic arch angle (SPA) measurement before labor onset can predict labor outcome among low-risk pregnant women. METHODS: 3D ultrasound volume was transperineally acquired from a series of nulliparous women with uncomplicated pregnancy at term before the onset of labor. SPA was measured offline using Oblique View Extended Imaging (OVIX) on each volume performed by an investigator not involved in the clinical management. Labor outcome was prospectively investigated in the whole study group. RESULTS: Overall, 145 women were enrolled in the study. Of these, 83 underwent spontaneous vaginal delivery, whereas obstetric intervention was performed in 62 cases (Cesarean section in 40 and vacuum extraction in 22). The SPA appeared to be significantly narrower in the women submitted to obstetric intervention compared with those undergoing spontaneous vaginal delivery (116.8 +/- 10.3 degrees vs. 123.7 +/- 9.6 degrees , p < 0.01). At multivariate analysis SPA and maternal age were identified as independent predictors of the mode of delivery. On the other hand, the duration of labor did not show a significant relationship with SPA. CONCLUSIONS: In low risk nulliparous women at term gestation, SPA measurement obtained by 3D ultrasound before the onset of labor seems to predict the likelihood of an obstetric intervention but not the duration of labor. PMID- 26555939 TI - The Efficient Derivation of Trophoblast Cells from Porcine In Vitro Fertilized and Parthenogenetic Blastocysts and Culture with ROCK Inhibitor Y-27632. AB - Trophoblasts (TR) are specialized cells of the placenta and play an important role in embryo implantation. The in vitro culture of trophoblasts provided an important tool to investigate the mechanisms of implantation. In the present study, porcine trophoblast cells were derived from pig in vitro fertilized (IVF) and parthenogenetically activated (PA) blastocysts via culturing in medium supplemented with KnockOut serum replacement (KOSR) and basic fibroblast growth factor (bFGF) on STO feeder layers, and the effect of ROCK (Rho-associated coiled coil protein kinases) inhibiter Y-27632 on the cell lines culture was tested. 5 PA blastocyst derived cell lines and 2 IVF blastocyst derived cell lines have been cultured more than 20 passages; one PA cell lines reached 110 passages without obvious morphological alteration. The derived trophoblast cells exhibited epithelium-like morphology, rich in lipid droplets, and had obvious defined boundaries with the feeder cells. The cells were histochemically stained positive for alkaline phosphatase. The expression of TR lineage markers, such as CDX2, KRT7, KRT18, TEAD4, ELF5 and HAND1, imprinted genes such as IGF2, PEG1 and PEG10, and telomerase activity related genes TERC and TERF2 were detected by immunofluorescence staining, reverse transcription PCR and quantitative real-time PCR analyses. Both PA and IVF blastocysts derived trophoblast cells possessed the ability to differentiate into mature trophoblast cells in vitro. The addition of Y-27632 improved the growth of both PA and IVF blastocyst derived cell lines and increased the expression of trophoblast genes. This study has provided an alternative highly efficient method to establish trophoblast for research focused on peri-implantation and placenta development in IVF and PA embryos. PMID- 26555941 TI - Generation of Gradients on a Microfluidic Device: Toward a High-Throughput Investigation of Spermatozoa Chemotaxis. AB - Various research tools have been used for in vitro detection of sperm chemotaxis. However, they are typically poor in maintenance of gradient stability, not to mention their low efficiency. Microfluidic device offers a new experimental platform for better control over chemical concentration gradient than traditional ones. In the present study, an easy-handle diffusion-based microfluidic chip was established. This device allowed for conduction of three parallel experiments on the same chip, and improved the performance of sperm chemotaxis research. In such a chip, there were six channels surrounding a hexagonal pool. The channels are connected to the hexagon by microchannels. Firstly, the fluid flow in the system was characterized; secondly, fluorescein solution was used to calibrate gradient profiles formed in the central hexagon; thirdly, sperm behavior was observed under two concentration gradients of progesterone (100 pM and 1 mM, respectively) as a validation of the device. Significant differences in chemotactic parameters were recognized between experimental and control groups (p < 0.05). Compared with control group, sperm motility was greatly enhanced in 1 mM group (p < 0.05), but no significant difference was found in 100 pM group. In conclusion, we proposed a microfluidic device for the study of sperm chemotaxis that was capable of generating multi-channel gradients on a chip and would help reduce experimental errors and save time in experiment. PMID- 26555942 TI - Genome-Wide Identification of New Reference Genes for qRT-PCR Normalization under High Temperature Stress in Rice Endosperm. AB - qRT-PCR is one of the most popular approaches to analyze specific gene expression level, and stably expressed reference genes are essential to obtain reliable results. However, many reference genes are only stable under certain circumstances and different reference genes might be required in different experiments. High temperature is a common stress that affects rice endosperm development and it has become a hot topic recently. Although study about reference genes at different developmental stages in rice has been reported, these genes may not be suitable to study high temperature mediated responses especially in endosperm. In our quest for proper reference genes to quantify gene expression in rice endosperm under high temperature, we studied 6 candidate genes selected from the transcriptome data and 11 housekeeping genes. All genes were analyzed with qRT-PCR and the expression stability was assessed with software geNorm and NormFinder. Fb15 and eIF-4a were identified as the two most stable genes in endosperm at different developmental stages, while high temperature treatment has a least effect on expression of Fb15 and UBQ5 in rice endosperm. Our results provide some good candidate reference genes for qRT-PCR normalization in rice endosperm under different temperatures. PMID- 26555943 TI - Evolutionary fate and implications of retrocopies in the African coelacanth genome. AB - BACKGROUND: The coelacanth is known as a "living fossil" because of its morphological resemblance to its fossil ancestors. Thus, it serves as a useful model that provides insight into the fish that first walked on land. Retrocopies are a type of novel genetic element that are likely to contribute to genome or phenotype innovations. Thus, investigating retrocopies in the coelacanth genome can determine the role of retrocopies in coelacanth genome innovations and perhaps even water-to-land adaptations. RESULTS: We determined the dS values, dN/dS ratios, expression patterns, and enrichment of functional categories for 472 retrocopies in the African coelacanth genome. Of the retrocopies, 85-355 were shown to be potentially functional (i.e., retrogenes). The distribution of retrocopies based on their dS values revealed a burst pattern of young retrocopies in the genome. The retrocopy birth pattern was shown to be more similar to that in tetrapods than ray-finned fish, which indicates a genomic transformation that accompanied vertebrate evolution from water to land. Among these retrocopies, retrogenes were more prevalent in old than young retrocopies, which indicates that most retrocopies may have been eliminated during evolution, even though some retrocopies survived, attained biological function as retrogenes, and became old. Transcriptome data revealed that many retrocopies showed a biased expression pattern in the testis, although the expression was not specifically associated with a particular retrocopy age range. We identified 225 Ensembl genes that overlapped with the coelacanth genome retrocopies. GO enrichment analysis revealed different overrepresented GO (gene ontology) terms between these "retrocopy-overlapped genes" and the retrocopy parent genes, which indicates potential genomic functional organization produced by retrotranspositions. Among the 225 retrocopy-overlapped genes, we also identified 46 that were coelacanth-specific, which could represent a potential molecular basis for coelacanth evolution. CONCLUSIONS: Our study identified 472 retrocopies in the coelacanth genome. Sequence analysis of these retrocopies and their parent genes, transcriptome data, and GO annotation information revealed novel insight about the potential role of genomic retrocopies in coelacanth evolution and vertebrate adaptations during the evolutionary transition from water to land. PMID- 26555944 TI - One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial. AB - BACKGROUND: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials. METHODS: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12. RESULTS: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months. CONCLUSIONS: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed. PMID- 26555946 TI - Simultaneous Quantification of the 8 Human Herpesviruses in Allogeneic Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of some of these infections on transplant outcomes is still unclear. A prospective survey on the incidence and clinical features of herpesviruses infections after HSCT has not yet been conducted in Brazilian patients, and the impact of these infections on HSCT outcome remains unclear. METHODS: We prospectively analyzed the incidence of infection of the eight human herpesviruses simultaneously in 1 045 peripheral blood samples from 98 allogeneic HSCT recipients. Samples were collected weekly starting at the time of transplant until day +100. All herpesviruses were screened and quantified in plasma by quantitative real-time polymerase chain reaction. Median follow up time was 24 months. RESULTS: The incidences of infection for each herpesvirus were as follows: cytomegalovirus (CMV), 44%; human herpesvirus [HHV] 6, 18%; HHV8, 6%; Epstein-Barr virus, 3%; herpes simplex virus 1, 3%; varicella zoster virus, 3%; HHV7, 2%; and herpes simplex virus 2, 1%. The CMV infection was significantly more frequent among adults and was associated with a higher risk of developing acute graft-versus-host disease. The HHV6 infection was significantly more frequent after umbilical cord blood transplant and was associated with an increased risk of platelet engraftment failure. There was no significant impact of these infections on the other transplant outcomes. CONCLUSIONS: Herpesviruses infections were uncommon after HSCT, except for CMV and HHV6, which, although relatively frequent, had no clinically relevant impact on the outcomes. PMID- 26555947 TI - The Role of TCF7L2 rs7903146 in Diabetes After Kidney Transplant: Results From a Single-Center Cohort and Meta-Analysis of the Literature. AB - BACKGROUND: Several genetic polymorphisms modulate the risk of posttransplant diabetes mellitus (PTDM), a complication associated with an increased morbidity and mortality after kidney transplantation; however, their clinical utility is still undefined. METHODS: Genetic analysis was performed in 464 kidney transplantation recipients to evaluate whether transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism is associated with the risk of PTDM and a meta-analysis of similar studies including our results was performed (total kidney transplantation recipients, n = 3105). A predictive model of PTDM was built on the basis of this polymorphism and clinical parameters. RESULTS: In our cohort, 163 patients possessed the CC genotype of rs7903146 (35.1%), 237 were CT (51.1%), and 64 were TT (13.8%): their 2 years PTDM incidence was, respectively, 7.8%, 11.9%, and 22.7%. At multivariate analysis, age (per year; hazard ratio [HR], 1.029; 95% confidence interval [95% CI], 1.005-1.054; P = 0.017), body mass index (25.0-29.9 vs <25.0; HR, 2.43; 95% CI, 1.40-4.23; P = 0.0018; >=30 vs <25.0; HR, 5.70; 95% CI, 2.77-11.74; P < 0.0001), TCF7L2 rs7903146 (per each T allele; HR, 1.81; 95% CI, 1.26-2.59; P = 0.001) and previous transplants (HR, 2.80; 95% CI, 1.39-5.64; P = 0.004) emerged as independent predictive factors for PTDM.Meta-analysis of present and 5 previous studies showed higher risk of PTDM in carriers of rs7903146 TT genotype (odds ratio, 1.95; 95% CI, 1.39-2.74; P < 0.0001) and absence of heterogeneity among studies (I = 0%).Inclusion of this polymorphism in a predictive model appeared to improve its ability to stratify patients according to the risk of PTDM. CONCLUSIONS: In renal transplant patients, TCF7L2 rs7903146 is strongly and independently associated with PTDM and might hold the potential to identify patients at risk for this complication. PMID- 26555945 TI - Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. AB - BACKGROUND: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age <=60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). CONCLUSIONS: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. PMID- 26555948 TI - Coronary Calcium Score May Replace Cardiovascular Risk Factors as Primary Risk Stratification Tool Before Kidney Transplantation. AB - BACKGROUND: Cardiac evaluation before kidney transplantation is recommended, but no unequivocal screening strategy has yet been identified. We investigated if coronary artery calcium score (CACS) can replace cardiovascular risk factor assessment in selection of kidney transplantation candidates for cardiac evaluation and the choice of noninvasive modality for diagnosing obstructive coronary artery disease (CAD). METHODS: We conducted a prospective study of 167 patients referred for pretransplantation cardiac evaluation. Patients underwent risk factor assessment, CACS, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), and invasive coronary angiography. In total, 138 patients completed all diagnostic tests. RESULTS: In patients with CAD (22%), the number of risk factors and CACS score were higher than that in patients without CAD. The accuracy evaluated by the receiver operating characteristic curve was higher for CACS than for risk factors, 0.85 versus 0.71 (P = 0.01). Adding CACS to the risk factor increased correct categorical net reclassification (0.58, P < 0.0001). Combining risk factors (>=3) with SPECT to identify patients with obstructive CAD resulted in less sensitivity (47% vs 80%) and higher specificity (94% vs 74%), compared with CCTA. In patients with low CACS (<400), SPECT had a lower sensitivity than CCTA (60% versus 80%) but the same specificity (80%). In patients with high CACS (>=400), SPECT had lower sensitivity than CCTA (50% vs 100%) and higher specificity (88% vs 8%). CONCLUSIONS: In kidney transplantation candidates, CACS outperformed risk factor assessment for predicting obstructive CAD and is a better tool for selecting patients and guiding the choice of noninvasive diagnostic modality in CAD. PMID- 26555949 TI - Calcineurin Inhibitors Downregulate HNF-1beta and May Affect the Outcome of HNF1B Patients After Renal Transplantation. AB - BACKGROUND: Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40-50%), and liver tests abnormalities (40-70%). In HNF1B patients who reach end-stage renal disease, single kidney transplantation (SKT) or combined kidney-pancreas transplantation can be considered. METHODS: A retrospective multicenter study including 18 HNF1B patients receiving SKT or kidney-pancreas transplantation, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure. RESULTS: After SKT, 50% of the HNF1B patients develop early posttransplantation diabetes mellitus, whereas 40% experience new-onset or severe worsening of preexisting abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independent of NFATc. CONCLUSIONS: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1beta transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach. PMID- 26555950 TI - Vascular effects of flavonoids. AB - Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clinical studies. In addition, extensive reviews have discussed the antiatherogenic effect of these polyphenols. However, limited studies have investigated the potential therapeutic vascular effects of these compounds. This review brings together some recent studies, to establish the different signaling pathways involved in the molecular mechanisms that underlie the vasodilation induced by flavonoids. PMID- 26555951 TI - Assessment of family functioning: evaluation of the General Functioning Scale in a Swedish Bariatric Sample. AB - BACKGROUND: The General Functioning Scale (GFS) was developed to assess self perceived overall family functioning. The scale has satisfactory psychometric properties, is internationally recognised and has been used in different contexts. However, no validated Swedish version is available. Healthy family functioning can support patients and help them adhere to treatment regimens. Moreover, it maintains the physical and emotional health and that of the family as a unit. Yet, there is limited information regarding family functioning postgastric bypass surgery. Thus, it is important to use validated instruments to understand family functioning in bariatric contexts. AIM: To evaluate aspects of reliability and validity in GFS in a Swedish bariatric sample, focusing on factor structure. METHOD: The Swedish version of the GFS (S-GFS) was administered on two occasions to 163 participants who had undergone gastric bypass surgery 6-8 weeks prior to testing. Internal consistency, temporal stability and construct validity were assessed. RESULTS: Data were positively skewed. The S-GFS showed good internal consistency (ordinal alpha = 0.92) with a sufficient overall mean interitem correlation (0.500) and adequate temporal stability (intraclass correlation coefficient = 0.833). After modifying response alternatives, confirmatory factor analysis indicated acceptable fit for a one-factor model. CONCLUSION: The scale is a promising tool for assessing family functioning in bariatric settings. The S-GFS showed satisfactory reliability - consistent with prior research - and acceptable validity in the study sample. This study contributes to the limited research on the scale's validity. However, the S-GFS needs to be evaluated in different cultural and clinical contexts, focusing on various aspects of validity and responsiveness (sensitivity to detect significant change over time) in different samples. PMID- 26555952 TI - Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database. AB - PURPOSE: The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. MATERIALS AND METHODS: We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. RESULTS: While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p <0.0001). In all other groups papillary renal cell cancer remained the most common type of nonclear renal cell cancer. CONCLUSIONS: It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis. PMID- 26555953 TI - A Prospective Randomized Controlled Trial of the Efficacy of External Physical Vibration Lithecbole after Extracorporeal Shock Wave Lithotripsy for a Lower Pole Renal Stone Less Than 2 cm. AB - PURPOSE: We evaluate the efficacy and safety of external physical vibration lithecbole in improving the clearance rates of lower pole renal stones after shock wave lithotripsy. MATERIALS AND METHODS: A total of 71 patients with lower pole renal stones (6 to 20 mm) were prospectively randomized into 2 groups. In the treatment group 34 patients were treated with external physical vibration lithecbole after shock wave lithotripsy. In the control group 37 patients underwent shock wave lithotripsy only. External physical vibration lithecbole was performed without anesthesia by the same team using the Friend-I External Physical Vibration Lithecbole (Fu Jian Da Medical Instrument Co., Ltd, Zhengzhou, China). The stone-free rate, stone expulsion rate, stone expulsion time and incidence of complications were monitored. RESULTS: External physical vibration lithecbole was successful in assisting the discharge of stone fragments. The stone-free status was 76.5% in the treatment group and 48.6% in the control group (p=0.008). Stone expulsion rates at day 1, week 1 and week 3 were 76.5% (26), 94.1% (32) and 94.1% (32) in the treatment group vs 43.2% (16), 73.0% (27) and 89.2% (33) in the control group, respectively. Mean stone fragment expulsion time was 11.2 minutes in the treatment group and 9.17 hours in the control group (p=0.016). There was no significant difference in complications between the 2 groups (p >0.05). CONCLUSIONS: External physical vibration lithecbole was efficacious in assisting the discharge of lower pole renal stone fragments and can be used as an adjunctive method of minimally invasive stone treatment. However, additional investigations are needed to confirm the efficacy. PMID- 26555954 TI - Salvage Percutaneous Nephrolithotomy: Analysis of Outcomes following Initial Treatment Failure. AB - PURPOSE: Percutaneous nephrolithotomy has high potential for morbidity or failure. There are limited data regarding risk factors for failure and to our knowledge no published reports of surgical outcomes in patients with prior failed attempts at percutaneous stone removal. MATERIALS AND METHODS: We identified patients referred to 3 medical centers after prior failed attempts at percutaneous nephrolithotomy. A retrospective chart review was performed to analyze reasons for initial failure and outcomes of salvage percutaneous nephrolithotomy. Outcomes were compared to those in a prospectively maintained database of more than 1,200 patients treated with a primary procedure. RESULTS: Salvage percutaneous nephrolithotomy was performed in 31 patients. Unsuitable access to the stone was the reason for failure in 80% of cases. Other reasons included infection, bleeding and inadequate instrument availability in 6.5% of cases each. Compared to patients who underwent primary percutaneous nephrolithotomy those treated with salvage were more likely to have staghorn calculi (61.3% vs 31.4%, p <0.01) and a larger maximum stone diameter (3.7 vs 2.5 cm, p <0.01), and require a secondary procedure (65.5% vs 42.1%, p <0.01). There was no significant difference between the cohorts in the remaining demographics or perioperative outcomes. All patients were deemed completely stone free except one who elected observation for a 3 mm nonobstructing fragment. CONCLUSIONS: Despite the more challenging nature and prior unsuccessful attempts at treatment, the outcomes of salvage percutaneous nephrolithotomy were no different from those of primary percutaneous nephrolithotomy when performed by experienced surgeons. PMID- 26555955 TI - Predictive Factors of Chronic Kidney Disease in Patients with Vesicoureteral Reflux Treated Surgically and Followed after Puberty. AB - PURPOSE: We delineated clinical features and determined predictors of chronic kidney disease during long-term postpubertal followup in patients with vesicoureteral reflux treated surgically. MATERIALS AND METHODS: We analyzed the data of 101 patients who were surgically treated for vesicoureteral reflux and had gone through puberty. Patients underwent preoperative and postoperative voiding cystourethrography to assess reflux status, and dimercaptosuccinic acid scan to assess renal cortical defects. We compared several variables preoperatively and postpubertally, including body mass index; blood urea nitrogen, creatinine and uric acid levels; estimated glomerular filtration rate; microalbuminuria; blood pressure; renal function and renal scarring. Kaplan-Meier analysis was used to predict chronic kidney disease-free survival rates throughout the followup periods. Cox regression model was adopted to identify independent predictors of chronic kidney disease. We defined chronic kidney disease as estimated glomerular filtration rate less than 60 ml/minute/1.73 m(2). RESULTS: Median followup was 100.0 months (IQR 69.0 to 136.5). Median age was 16 years at last followup (IQR 14 to 18). A total of 11 patients (10.9%) were diagnosed with de novo chronic kidney disease during postpubertal followup. It is noteworthy that serum uric acid levels (HR 1.96) and presence of high grade reflux (HR 7.40) were significant predictors of chronic kidney disease on multivariate analysis. CONCLUSIONS: In children who were treated surgically for vesicoureteral reflux preoperative uric acid levels and high grade reflux were independent predictors of de novo chronic kidney disease during postpubertal followup. Our results offer valuable information for predicting long-term renal outcomes in patients with vesicoureteral reflux treated surgically. PMID- 26555956 TI - Root Causes and Modifiability of 30-Day Hospital Readmissions after Radical Cystectomy for Bladder Cancer. AB - PURPOSE: Radical cystectomy is associated with high complication and rehospitalization rates. An understanding of the root causes of hospital readmissions and the modifiability of factors contributing to readmissions may decrease the morbidity associated with radical cystectomy. We characterize the indications for rehospitalization following radical cystectomy, and determine whether these indications represent immutable patient disease and procedure factors or whether they are modifiable. MATERIALS AND METHODS: From MarketScan(r) databases we identified patients younger than 65 years with a diagnosis of bladder cancer who underwent radical cystectomy between 2008 and 2011 and were readmitted to the hospital within 30 days of radical cystectomy. All associated ICD-9 codes in the index admission, subsequent outpatient claims and readmission claims were independently reviewed by 3 surgeons to determine a root cause of rehospitalization. Causes were broadly categorized as medical, surgical or infectious, and reviewers determined whether the readmission was modifiable. Multivariate logistical regression models were used to identify factors associated with rehospitalization. RESULTS: A total of 1,163 patients were included in the study and 242 (21%) were readmitted to the hospital within 30 days. Of these readmissions 26% were considered modifiable (kappa=0.71). Of the nonmodifiable readmissions an infectious cause accounted for 52% and a medical cause accounted for 48%, whereas of the modifiable readmissions 62% were due to surgical causes, 30% to medical and 8% to infectious causes. On multivariate analysis only discharge to a skilled nursing facility was associated with modifiable (OR 6.12, 95% CI 2.32-16.14) or nonmodifiable (OR 3.27, 95% CI 1.63 6.53) hospital readmissions. CONCLUSIONS: The majority of rehospitalizations after radical cystectomy are attributable its inherent morbidity. However, optimization of aspects of peri-cystectomy care could minimize the morbidity of radical cystectomy. PMID- 26555957 TI - Frameworks for Disaster Research and Evaluation. PMID- 26555958 TI - Basal Lamina Mimetic Nanofibrous Peptide Networks for Skeletal Myogenesis. AB - Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells' growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, "IKVAV", and fibronectin-derived well known adhesive sequence, "RGD", into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes. PMID- 26555959 TI - Interfacial adsorption and surfactant release characteristics of magnetically functionalized halloysite nanotubes for responsive emulsions. AB - Magnetically responsive oil-in-water emulsions are effectively stabilized by a halloysite nanotube supported superparamagnetic iron oxide nanoparticle system. The attachment of the magnetically functionalized halloysite nanotubes at the oil water interface imparts magnetic responsiveness to the emulsion and provides a steric barrier to droplet coalescence leading to emulsions that are stabilized for extended periods. Interfacial structure characterization by cryogenic scanning electron microscopy reveals that the nanotubes attach at the oil-water interface in a side on-orientation. The tubular structure of the nanotubes is exploited for the encapsulation and release of surfactant species that are typical of oil spill dispersants such as dioctyl sulfosuccinate sodium salt and polyoxyethylene (20) sorbitan monooleate. The magnetically responsive halloysite nanotubes anchor to the oil-water interface stabilizing the interface and releasing the surfactants resulting in reduction in the oil-water interfacial tension. The synergistic adsorption of the nanotubes and the released surfactants at the oil-water interface results in oil emulsification into very small droplets (less than 20MUm). The synergy of the unique nanotubular morphology and interfacial activity of halloysite with the magnetic properties of iron oxide nanoparticles has potential applications in oil spill dispersion, magnetic mobilization and detection using magnetic fields. PMID- 26555960 TI - Barrierless growth of precursor-free, ultrafast laser-fragmented noble metal nanoparticles by colloidal atom clusters - A kinetic in situ study. AB - Unintended post-synthesis growth of noble metal colloids caused by excess amounts of reactants or highly reactive atom clusters represents a fundamental problem in colloidal chemistry, affecting product stability or purity. Hence, quantified kinetics could allow defining nanoparticle size determination in dependence of the time. Here, we investigate in situ the growth kinetics of ps pulsed laser fragmented platinum nanoparticles in presence of naked atom clusters in water without any influence of reducing agents or surfactants. The nanoparticle growth is investigated for platinum covering a time scale of minutes to 50days after nanoparticle generation, it is also supplemented by results obtained from gold and palladium. Since a minimum atom cluster concentration is exceeded, a significant growth is determined by time resolved UV/Vis spectroscopy, analytical disc centrifugation, zeta potential measurement and transmission electron microscopy. We suggest a decrease of atom cluster concentration over time, since nanoparticles grow at the expense of atom clusters. The growth mechanism during early phase (<1day) of laser-synthesized colloid is kinetically modeled by rapid barrierless coalescence. The prolonged slow nanoparticle growth is kinetically modeled by a combination of coalescence and Lifshitz-Slyozov-Wagner kinetic for Ostwald ripening, validated experimentally by the temperature dependence of Pt nanoparticle size and growth quenching by Iodide anions. PMID- 26555961 TI - Influence of Ag-Au microstructure on the photoelectrocatalytic performance of TiO2 nanotube array photocatalysts. AB - In this work, vertically-aligned TiO2 nanotube arrays (TiO2 NTs) were grown on Ti substrates via a facile electrochemical anodization method followed by calcinations. Then, Ag-Au alloy nanoparticles and Ag@Au core-shell nanoparticles were deposited on the obtained TiO2 NTs via UV reduction and displacement reaction, respectively. X-ray diffraction, scanning electron microscopy and transmission electron microscopy indicated that Ag-Au alloy nanoparticles and Ag@Au core-shell nanoparticles grew uniformly on the walls of TiO2 NTs. Investigation results from removal of methyl orange (MO) and Cr(IV) ions indicated that the as-prepared bimetal plasmonic photocatalysts exhibited excellent photoelectrocatalytic (PEC) activities. The influences of Ag-Au alloy and core-shell microstructures on PEC properties of TiO2 NTs were investigated and the TiO2 NTs/Ag@Au photocatalyst showed more outstanding PEC removal efficiency than that of TiO2 NTs/Ag-Au due to the regular core-shell microstructure and low recombination of photogenerated electrons and holes. PMID- 26555962 TI - High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan. AB - Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation. PMID- 26555964 TI - Pentoxifylline Loaded Floating Microballoons: Design, Development and Characterization. AB - The floating microballoons have been utilized to obtain prolonged and uniform release in the stomach. The objective of the present study involves design, development, and characterization of pentoxifylline loaded floating microballoons to prolong their gastric residence time. Pentoxifylline (trisubstituted xanthine derivative) loaded microballoons were prepared by the solvent evaporation technique using different concentrations of polymers like HPMC K4M and ethyl cellulose (EC) in ethyl alcohol and dichloromethane organic solvent system. Microballoons were characterized for their particle size, surface morphology, production yield, loading efficiency, buoyancy percentage, and in vitro drug release studies. From the characterization it was observed that increases in amount of polymers (HPMC K4M and EC) led to increased particle size, loading efficiency, and buoyancy percentage, and retarded drug release. The particle size, particle yield, loading efficiency, buoyancy percentage and in vitro drug release for optimized formulation (F3) were found to be 104.0 +/- 2.87 um, 80.89 +/- 2.24%, 77.85 +/- 0.61%, 77.52 +/- 2.04%, and 82.21 +/- 1.29%, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non Fickian) diffusion. The in vitro result showed that formulations comprised of varying concentrations of ethyl cellulose in higher proportion exhibited much retarded drug release as compared to formulations comprised of higher proportion of varying concentrations of HPMC K4M. PMID- 26555963 TI - Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions. AB - Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. PMID- 26555965 TI - Preparation and Comparative Bioavailability Studies of Indomethacin-Loaded Cetyl Alcohol Microspheres. AB - The purpose of the present study was to compare the in vitro release and to find out whether the bioavailability of a 75 mg indomethacin capsule (Microcid SR) was equivalent to optimized formulation (indomethacin-loaded cetyl alcohol microspheres). Indomethacin-loaded cetyl alcohol microspheres were prepared by meltable emulsified cooling-induced technique. Surface morphology of microspheres has been evaluated using scanning electron microscopy. A single dose, randomized, complete cross over study of IM microspheres was carried out on 10 healthy male and female Albino sheep's under fasting conditions. The plasma was separated and the concentrations of the drug were determined by HPLC-UV method. Plasma indomethacin concentrations and other pharmacokinetic parameters obtained were statistically analyzed. The SEM images revealed the spherical shape of fat microspheres, and more than 98.0% of the isolated microspheres were in the size range 12-32 MUm. DSC, FTIR spectroscopy and stability studies indicated that the drug after encapsulation with fat microspheres was stable and compatible. Both formulations were found to be bioequivalent as evidenced by in vivo studies. Based on this study, it can be concluded that cetyl alcohol microspheres and Microcid SR capsule are bioequivalent in terms of the rate and extent of absorption. PMID- 26555966 TI - Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice. AB - We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15 liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80-90 nm, the sizes of C5-, C10- and C15 liposome/siRNA complexes (lipoplexes) were about 1,700-1,800 nm, and those of T5 , T10-, and T15-lipoplexes were about 550-780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally. PMID- 26555967 TI - Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation. AB - The current study deals with the development and optimization of ispaghula (Plantago ovata F.) husk mucilage- (IHM-) alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA) to IHM and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), as well as cumulative drug release after 10 hours (R10 h, %), were optimized using 3(2) factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited 94.43 +/- 4.80% w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order) pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration. PMID- 26555968 TI - Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics. AB - This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT IR were employed to investigate the evolution of ARTM's dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM. PMID- 26555969 TI - Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo. AB - Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin's radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin's effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1alpha expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1alpha. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1alpha expression. PMID- 26555970 TI - Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability. AB - Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200-250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. PMID- 26555971 TI - HPLC Quantification of Phenolic Acids from Vetiveria zizanioides (L.) Nash and Its Antioxidant and Antimicrobial Activity. AB - Extraction procedure was standardized and for the soluble, glycoside, and wall bound fractions of phenolic acids from Vetiveria zizanioides. The water soluble alkaline extract which represents the cell wall-bound fraction contained the highest amount of phenolic acids (2.62 +/- 1.2 MUM/g fwt GA equivalents). Increased phenolic content in the cell wall indicates more lignin deposition which has an important role in plant defense and stress mitigation. Antioxidant property expressed as percentage TEAC value obtained by ABTS assay was correlated with the amount of phenolic acids and showed a Pearson's coefficient 0.988 (significant at 0.01 level). The compounds p-coumaric acid, p-dihydroxybenzoic acid, and ferulic acid were detected in the acidic extracts by HPLC analysis. The plant extracts exhibited considerable antimicrobial activity against tested bacterial and fungal strains. PMID- 26555972 TI - Dissolution Enhancement of Rosuvastatin Calcium by Liquisolid Compact Technique. AB - In present investigation liquisolid compact technique is investigated as a tool for enhanced dissolution of poorly water-soluble drug Rosuvastatin calcium (RVT). The model drug RVT, a HMG-Co A reductase inhibitor was formulated in form of directly compressed tablets and liquisolid compacts; and studied for in-vitro release characteristics at different dissolution conditions. In this technique, liquid medications of water insoluble drugs in non-volatile liquid vehicles can be converted into acceptably flowing and compressible powders. Formulated systems were assessed for precompression parameters like flow properties of liquisolid system, Fourior transform infra red spectra (FTIR) analysis, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and post compression parameters like content uniformity, weight variation, hardness and friability, disintegration test, wetting time, in vitro dissolution studies, effect of dissolution volume on drug release rate, and estimation of fraction of molecularly dispersed drug in liquid medication. As liquisolid compacts demonstrated significantly higher drug release rates, we lead to conclusion that it could be a promising strategy in improving the dissolution of poor water soluble drugs and formulating immediate release solid dosage forms. PMID- 26555973 TI - Self-Microemulsifying Drug Delivery System: Formulation and Study Intestinal Permeability of Ibuprofen in Rats. AB - The study was aimed at developing a self-microemulsifying drug delivery system (SMEDDS) of Ibuprofen for investigating its intestinal transport behavior using the single-pass intestinal perfusion (SPIP) method in rat. Methods. Ibuprofen loaded SMEDDS (ISMEDDS) was developed and was characterized. The permeability behavior of Ibuprofen over three different concentrations (20, 30, and 40 ug/mL) was studied in each isolated region of rat intestine by SPIP method at a flow rate of 0.2 mL/min. The human intestinal permeability was predicted using the Lawrence compartment absorption and transit (CAT) model since effective permeability coefficients (P eff) values for rat are highly correlated with those of human, and comparative intestinal permeability of Ibuprofen was carried out with plain drug suspension (PDS) and marketed formulation (MF). Results. The developed ISMEDDS was stable, emulsified upon mild agitation with 44.4 nm +/- 2.13 and 98.86% +/- 1.21 as globule size and drug content, respectively. Higher P eff in colon with no significant P eff difference in jejunum, duodenum, and ileum was observed. The estimated human absorption of Ibuprofen for the SMEDDS was higher than that for PDS and MF (P < 0.01). Conclusion. Developed ISMEDDS would possibly be advantageous in terms of minimized side effect, increased bioavailability, and hence the patient compliance. PMID- 26555974 TI - Health Technology Assessment Fireside: Antibiotic Prophylaxis and Dental Treatment in Canada. AB - Objectives. This paper discusses the controversies surrounding the antibiotic prophylaxis preceding dental interventions within the following research question: how effective is dental antibiotic prophylaxis in preventing comorbidity and complications in those at risk? Methods. A synthesis of the available literature regarding antibiotic prophylaxis in dentistry was conducted under the lenses of Kazanjian's framework for health technology assessment with a focus on economic concerns, population impact, social context, population at risk, and the effectiveness of the evidence to support its use. Results. The papers reviewed show that we have been using antibiotic prophylaxis without a clear and full understanding of its benefits. Although the first guideline for antibiotic prophylaxis was introduced in 1990, it has been revised on several occasions, from 1991 to 2011. Evidence-based clinical guidelines are yet to be seen. Conclusions. Any perceived potential benefit from administering antibiotic prophylaxis before dental procedures must be weighed against the known risks of lethal toxicity, allergy, and development, selection, and transmission of microbial resistance. The implications of guideline changes and lack of evidence for the full use of antibiotic prophylaxis for the teaching of dentistry have to be further discussed. PMID- 26555975 TI - Some Pharmacodynamic Aspects of Cefepime. AB - Some pharmacodynamic effects of cefepime, a new injectable semisynthetic cephalosporin, were studied in laboratory animals and the following results were obtained. Cefepime maximally stimulated isolated guinea pig's ileum, rat's colon (80 MUg/mL bath), and rabbit's duodenum (400 MUg/mL bath). Contrarily, complete relaxation of isolated rat's fundic strip was produced by 80 MUg/mL bath. Effects of cefepime on isolated rat's uterine muscle were different according to stage of sex cycle. Cefepime did not induce any effects on the resting tonus of isolated guinea pig's tracheal chain and rabbit's aortic strip. Concentrations of 200 and 400 MUg/mL bath induced marked inhibition in the force of muscular twitches of the isolated frog's gastrocnemius muscle which was less potent than that induced by procaine hydrochloride 2%. Cefepime completely blocked the neuromuscular transmission of frog's rectus abdominis muscle (40 MUg/mL bath) and rat's phrenic nerve hemidiaphragm preparation (200 MUg/mL bath). This blockade was reversed by acetylcholine and neostigmine. Cefepime produced dose-dependent negative inotropic effect on isolated rabbit's heart and guinea pig's auricles. There were no changes in blood pressure and rate of respiration in anaesthetized dog after cefepime injection. These findings indicate that cefepime has a low potential to produce adverse reactions at therapeutic doses. PMID- 26555976 TI - Innovative Approach for Interstitial Cystitis: Vaginal Pessaries Loaded Diazepam A Preliminary Study. AB - Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated. PMID- 26555977 TI - Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design. AB - The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X 1), HPMC K100M (X 2), and dicalcium phosphate (X 3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y 1) and at 8th hour (Y 2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid. PMID- 26555978 TI - Simultaneous Determination of Clidinium Bromide and Chlordiazepoxide in Combined Dosage Forms by High-Performance Liquid Chromatography. AB - A sensitive and precise RP-HPLC method has been developed for the simultaneous estimation of clidinium bromide (CDB) and chlordiazepoxide (CDZ) in pure and pharmaceutical formulations. The separation was achieved on a Nucleodur C8 (250 * 4.6 mm i.d., 5 MUm particle size) column at 25 degrees C. CH3CN-MeOH-NH4OAc 0.1M (30 : 40 : 30, v/v/v) was used as the mobile phase at a flow rate of 1.0 mL min( 1) and detector wavelength at 218 nm. Almotriptan (ALT) was used as internal standard. The validation of the proposed method was carried out for linearity, accuracy, precision, LOD, LOQ, and robustness. The method showed good linearity in the ranges of 2.5-300.0 and 3.0-500.0 MUg mL(-1) for CDB and CDZ, respectively. The percentage recovery obtained for CDB and CDZ was 100.40-103.38 and 99.98-105.59%, respectively. LOD and LOQ were 0.088 and 0.294 MUg mL(-1) for CDB and 0.121 and 0.403 MUg mL(-1) for CDZ, respectively. The proposed method was successfully applied to the determination of CDB and CDZ in combined dosage forms and the results tallied well with the label claim. PMID- 26555979 TI - Preparation and Evaluation of Valsartan Liquid Filling Formulations for Soft Gels. AB - The present investigation includes the preparation of liquid filling formulations for soft gels using an antihypertensive drug, valsartan (VAL), in order to improve its dissolution properties and thereby its bioavailability. Formulations were prepared using excipients like polyethylene glycol 400 (PEG 400), propylene glycol (PG), polyvinylpyrrolidone (PVP K-30), antioxidants, ethanol, and purified water. Prepared formulations were evaluated for appearance, pH, drug content percentage, viscosity, stability, and in vitro dissolution studies. The compatibility between the drug and excipients in formulations was confirmed by FTIR spectra. The drug contents were in the range of 99.62-99.63 and the viscosity was in the range of 60.9-591.7 cps with all the formulations developed. Formulations containing 10 mg PVP K 30 gave better dissolution properties when compared to formulations without PVP K 30, and a complete drug dissolution was observed within 10 min and followed the first-order release kinetics. Stability studies were conducted for selected formulations (F4-F9) for a period of 6 months at room temperature (~30 degrees C/65% RH). From the studies, it can be concluded that VAL liquid filling formulations for soft gels were successfully prepared with in vitro dissolution properties superior when compared to VAL itself. PMID- 26555980 TI - Quantification of Lumefantrine in Human Plasma Using LC-MS/MS and Its Application to a Bioequivalence Study. AB - An analytical method based on protein precipitation has been developed and validated for analysis of lumefantrine in human plasma. Artesunate was used as an internal standard for lumefantrine. Inertsil ODS column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-3000 system. The total run time was 2.5 minutes. The proposed method has been validated with linear range of 200-20000 ng/mL for lumefantrine. The intrarun and interrun precision values are within 6.66% and 5.56%, respectively, for lumefantrine at the lower limit of quantification level. The overall recovery for lumefantrine and artesunate was 93.16% and 91.05%, respectively. This validated method was used successfully for analysis of plasma samples from a bioequivalence study. PMID- 26555981 TI - Determination of Zalcitabine in Medicaments by Differential Pulse Voltammetry. AB - The zalcitabine (ddC) has been extensively used in the treatment of HIV patients due to its antiretroviral activity. The quality control of this active principle in medications is of outstanding importance to public health. The principal objective of the current study was the development of an alternative analytical methodology for the zalcitabine determination using a voltammetric process. The zalcitabine gives a reduction peak (at -1.22 V versus Ag/AgCl) at the hanging mercury drop electrode (HMDE). The differential pulse voltammetric response is evaluated with respect to the scan rate (20 mV/s), pulse amplitude (50 mV), support electrolyte (Clark-Lubs buffer), pH (2.0), and other variables. The response is linear over the 10.0 to 28.0 mg/L (47 to 133 MUM) concentration range, and the detection limit is 2.08 mg/L. The validation of this method was realized using a governmental Brazilian document (Inmetro, 2007) and the results are reported for medication drugs. PMID- 26555982 TI - Optimization of Metronidazole Emulgel. AB - The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections. PMID- 26555983 TI - Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli. AB - Escherichia coli (E. coli) is associated with necrotizing fasciitis (type I) and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1) to ascertain the level of antibacterial activity. The n-propyl (drug 2), n-pentyl (drug 3), and n-octyl (drug 4) esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became -0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms(2), 63.6 Angstroms(2), 63.6 Angstroms(2), and 63.6 Angstroms(2), respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p ) and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli. PMID- 26555984 TI - Solubility Enhancement of Raloxifene Using Inclusion Complexes and Cogrinding Method. AB - The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-beta-cyclodextrin (HPbetaCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug MGG cogrind mixtures were characterized by differential scanning calorimetry, X ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPbetaCD complexation method showed significant enhancement of drug solubility. PMID- 26555985 TI - Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery. AB - The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID- 26555986 TI - Quality Assessment of Serially Ultradiluted and Agitated Drug Digitalis purpurea by Emission Spectroscopy and Clinical Analysis of Its Effect on the Heart Rate of Indian Bufo melanostictus. AB - The investigation of ultradiluted (homeopathic) drugs is extremely interesting and challenging, and from that point of view this study shows novelty. A study of in vivo changes in heart rate of the Indian Bufo melanostictus caused by commercially available serially ultra-diluted and agitated extract of Digitalis purpurea has been tried in order to understand their pharmacological role. RR interval (of ECG) was compared after intraperitoneal administration of serially diluted and agitated Digitalis purpurea extract, diluent rectified spirit, and Digoxin in anesthetized animals. The study revealed statistically significant changes in the heart rate after application of these drugs except in case of Digoxin and the 200th serial dilution of Digitalis purpurea. The duration of RR intervals after application of the drugs was corroborative of the effect of Digoxin and Digitalis purpurea extract up to 30th dilution. Emission spectra were obtained for the experimental ultra-diluted Digitalis purpurea extract and Digoxin to identify and characterize them. The observed RR pattern and emission spectra show an association. The quality assessment of the commercial ultra diluted organic drugs obtained from natural products may be initiated by monitoring in vivo studies on animal models. PMID- 26555987 TI - Development of Orodispersible Tablets of Candesartan Cilexetil- beta cyclodextrin Complex. AB - The aim of this study was to investigate the use of inclusion complexation technique employing beta-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with beta-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved beta cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. PMID- 26555988 TI - In Vitro and In Vivo Evaluation of Oxatomide beta -Cyclodextrin Inclusion Complex. AB - The objective of this study was to evaluate the influence of oxatomide beta cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide beta-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and beta-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency (P < 0.05) compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with beta-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide. PMID- 26555989 TI - Study on Mixed Solvency Concept in Formulation Development of Aqueous Injection of Poorly Water Soluble Drug. AB - In the present investigation, mixed-solvency approach has been applied for the enhancement of aqueous solubility of a poorly water- soluble drug, zaltoprofen (selected as a model drug), by making blends (keeping total concentrations 40% w/v, constant) of selected water-soluble substances from among the hydrotropes (urea, sodium benzoate, sodium citrate, nicotinamide); water-soluble solids (PEG 4000, PEG-6000); and co-solvents (propylene glycol, glycerine, PEG-200, PEG-400, PEG-600). Aqueous solubility of drug in case of selected blends (12 blends) ranged from 9.091 +/- 0.011 mg/ml-43.055 +/- 0.14 mg/ml (as compared to the solubility in distilled water 0.072 +/- 0.012 mg/ml). The enhancement in the solubility of drug in a mixed solvent containing 10% sodium citrate, 5% sodium benzoate and 25 % S cosolvent (25% S cosolvent contains PEG200, PEG 400, PEG600, Glycerine and Propylene glycol) was more than 600 fold. This proved a synergistic enhancement in solubility of a poorly water-soluble drug due to mixed cosolvent effect. Each solubilized product was characterized by ultraviolet and infrared techniques. Various properties of solution such as pH, viscosity, specific gravity and surface tension were studied. The developed formulation was studied for physical and chemical stability. This mixed solvency shall prove definitely a boon for pharmaceutical industries for the development of dosage form of poorly water soluble drugs. PMID- 26555990 TI - Ufasomes Mediated Cutaneous Delivery of Dexamethasone: Formulation and Evaluation of Anti-Inflammatory Activity by Carrageenin-Induced Rat Paw Edema Model. AB - The purpose of study is to formulate and evaluate ufasomal gel of dexamethasone. Ufasomal suspension was made by sonication method using different concentrations of Span 80, Span 20 and cholesterol along with 25 mg of drug. Ufasomal gel was formulated by hydration method using carbopol 940. Ufasomal vesicles appeared as spherical and multilamellar under Transmission Electron Microscope. Ufasomal formulation prepared with drug to oleic acid molar ratio 8:2 (UF-2) produced greater number of vesicles and greater entrapment efficiency. UF-2 was optimized for further evaluation. The transdermal permeation and skin partitioning of from optimized formulation was significantly higher (P < 0.05) as compared to plain drug and plain gel formulation which is due to presence of surfactant acting as permeation enhancer. Permeation of optimized formulation was found to be about 4.7 times higher than plain drug gel. Anti-inflammatory activity evaluated by inhibition Carrageenan induced rat paw edema model. Significant reduction of edema (P < 0.10) was observed in comparison to the commercial product. Hence oleic acid based vesicles can be used as alternate carrier for topical delivery. PMID- 26555991 TI - Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement. AB - Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 MUg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route. PMID- 26555993 TI - Hydrotropic Solubilization by Urea Derivatives: A Molecular Dynamics Simulation Study. AB - Hydrotropy is a phenomenon where the presence of a large quantity of one solute enhances the solubility of another solute. The mechanism of this phenomenon remains a topic of debate. This study employed molecular dynamics simulation to investigate the hydrotropic mechanism of a series of urea derivatives, that is, urea (UR), methylurea (MU), ethylurea (EU), and butylurea (BU). A poorly water soluble compound, nifedipine (NF), was used as the model solute that was solubilized. Structural, dynamic, and energetic changes upon equilibration were analyzed to supply insights to the solubilization mechanism. The study demonstrated that NF and urea derivatives underwent significant nonstoichiometric molecular aggregation in the aqueous solution, a result consistent with the self aggregation of urea derivatives under the same conditions. The analysis of hydrogen bonding and energy changes revealed that the aggregation was driven by the partial restoration of normal water structure. The energetic data also suggested that the promoted solubilization of NF is favored in the presence of urea derivatives. While the solutes aggregated to a varying degree, the systems were still in single-phase liquid state as attested by their active dynamics. PMID- 26555992 TI - Seasonal Monitoring of Cardiovascular and Antiulcer Agents' Concentrations in Stream Waters Encompassing a Capital City. AB - Nowadays monitoring pharmaceutical residues from surface waters is a widespread analytical task. Most of the studies are conducted from river waters or sewage treatment plants and mainly in Western Europe or North America. Such studies are seldom published from Eastern Europe, especially from stream waters, even though the prescription and consumption patterns of drugs as well as wastewater treatment procedures are very dissimilar. In Hungary the active substance of the most often prescribed drugs are cardiovascular and antiulcer agents. Hence in our study compounds belonging to these two groups were seasonally monitored in two main streams encompassing the Buda side of the Hungarian capital city and flowing into the Danube. To obtain data on the occurrence, fate, and seasonal variation of the compounds, samples were taken from altogether eleven points located near wastewater treatment plants and confluences. The results gave no identifiable pattern in the seasonal variation of concentrations but the contribution of the tributaries and wastewater treatment plants could be followed as expected. From the runoff corrected estuary concentrations the annual contribution of these streams to pharmaceutical pollution of the Danube could be estimated to be in excess of 1 kilogram for atenolol, famotidine, metoprolol, ranitidine, and sotalol. PMID- 26555994 TI - Use of the Charge Transfer Reactions for the Spectrophotometric Determination of Risperidone in Pure and in Dosage Forms. AB - The aim of study was to develop and validate two simple, sensitive, and extraction-free spectrophotometric methods for the estimation of risperidone in both pure and pharmaceutical preparations. They are based on the charge transfer complexation reactions between risperidone (RSP) as n-electron donor and p chloranilic acid (p-CA) in method A and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in method B as pi-acceptors. In method A, RSP reacts with p-CA in methanol to produce a bright pink-colored chromogen measured at 530 nm whereas, in method B, RSP reacts with DDQ in dichloromethane to form orange-colored complex with a maximum absorption at 460 nm. Beer's law was obeyed in the concentration range of 0-25 and 0-50 MUg/mL with molar absorptivity of 1.29 * 10(4) and 0.48 * 10(4) L/moL/cm for RSP in methods A and B, respectively. The effects of variables such as reagents, time, and stability of the charge transfer complexes were investigated to optimize the procedures. The proposed methods have been successfully applied to the determination of RSP in pharmaceutical formulations. Results indicate that the methods are accurate, precise, and reproducible (relative standard deviation <2 %). PMID- 26555995 TI - Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles. AB - Neurodegeneration is characterized by progressive loss of structure and function of neurons. Several therapeutic methods and drugs are available to alleviate the symptoms of these diseases. The currently used delivery strategies such as implantation of catheters, intracarotid infusions, surgeries, and chemotherapies are invasive in nature and pose a greater risk of postsurgical complications, which can have fatal side effects. The current study utilizes a peptide (TAT and MGF) tagged PEGylated chitosan nanoparticle formulation for siRNA delivery, administered intranasally, which can bypass the blood brain barrier. The study investigates the optimal dose, duration, biodistribution, and toxicity, of the nanoparticle-siRNA formulation, in-vivo. The results indicate that 0.5 mg/kg of siRNA is delivered successfully to the hippocampus, thalamus, hypothalamus, and Purkinje cells in the cerebellum after 4 hrs of post intranasal delivery. The results indicate maximum delivery to the brain in comparison to other tissues with no cellular toxic effects. This study shows the potential of peptide-tagged PEGylated chitosan nanoparticles to be delivered intranasally and target brain tissue for the treatment of neurological disorders. PMID- 26555996 TI - Preparation, Characterization, and In Vivo Evaluation of Olanzapine Poly(D,L lactide-co-glycolide) Microspheres. AB - The aim of this study was to prepare injectable depot formulations of Olanzapine using four poly(D,L-lactide-co-glycolide) (PLGA) polymers of varying molecular weight and copolymer composition, and evaluate in vivo performance in rats. In vivo release profiles from the formulations were governed chiefly by polymer molecular weight and to a lesser extent, copolymer composition. Formulations A and B, manufactured using low molecular weight PLGA and administered at 10 mg/kg dose, released drug within 15 days. Formulation C, prepared from intermediate molecular weight PLGA and administered at 20 mg/kg dose, released drug in 30 days, while Formulation D, manufactured using a high molecular weight polymer and administered at 20 mg/kg dose, released drug in 45 days. A simulation of multiple dosing at 7- and 10-day intervals for Formulations A and B revealed that steady state was achieved within 7-21 days and 10-30 days, respectively. Similarly, simulations at 15-day intervals for Formulations C and D indicated that steady state levels were reached during days 15-45. Overall, steady state levels for 7-, 10-, or 15-day dosing ranged between 45 and 65 ng/mL for all the formulations, implying that Olanzapine PLGA microspheres can be tailored to treat patients with varying clinical needs. PMID- 26555997 TI - Quantum Dot-Loaded Liposomes to Evaluate the Behavior of Drug Carriers after Oral Administration. AB - We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy. PMID- 26555998 TI - Analysis of Hydroxy Fatty Acids from the Pollen of Brassica campestris L. var. oleifera DC. by UPLC-MS/MS. AB - Ultraperformance liquid chromatography coupled with negative electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) was used to determine 7 hydroxy fatty acids in the pollen of Brassica campestris L. var. oleifera DC. All the investigated hydroxy fatty acids showed strong deprotonated molecular ions [M-H](-), which underwent two major fragment pathways of the allyl scission and the beta-fission of the alcoholic hydroxyl group. By comparison of their molecular ions and abundant fragment ions with those of reference compounds, they were tentatively assigned as 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (1), 10,11,12-trihydroxy (7Z,14Z)-heptadecadienoic acid (2), 7,15,16-trihydroxy-9Z,12Z-octadecadienoic acid (3), 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (4), 15-hydroxy-6Z,9Z,12Z octadecatrienoic acid (5), 15-hydroxy-9Z,12Z- octadecadienoic acid (6), and 15 hydroxy-12Z-octadecaenoic acid (7), respectively. Compounds 3, 5, and 7 are reported for the first time. PMID- 26555999 TI - Biological Atomic Force Microscopy for Imaging Gold-Labeled Liposomes on Human Coronary Artery Endothelial Cells. AB - Although atomic force microscopy (AFM) has been used extensively to characterize cell membrane structure and cellular processes such as endocytosis and exocytosis, the corrugated surface of the cell membrane hinders the visualization of extracellular entities, such as liposomes, that may interact with the cell. To overcome this barrier, we used 90 nm nanogold particles to label FITC liposomes and monitor their endocytosis on human coronary artery endothelial cells (HCAECs) in vitro. We were able to study the internalization process of gold-coupled liposomes on endothelial cells, by using AFM. We found that the gold-liposomes attached to the HCAEC cell membrane during the first 15-30 min of incubation, liposome cell internalization occurred from 30 to 60 min, and most of the gold labeled liposomes had invaginated after 2 hr of incubation. Liposomal uptake took place most commonly at the periphery of the nuclear zone. Dynasore monohydrate, an inhibitor of endocytosis, obstructed the internalization of the gold liposomes. This study showed the versatility of the AFM technique, combined with fluorescent microscopy, for investigating liposome uptake by endothelial cells. The 90 nm colloidal gold nanoparticles proved to be a noninvasive contrast agent that efficiently improves AFM imaging during the investigation of biological nanoprocesses. PMID- 26556000 TI - Influence of Air Temperature and Humidity on Dehydration Equilibria and Kinetics of Theophylline. AB - The effect of hygrothermal conditions (air temperature and relative humidity) on the dehydration of theophylline monohydrate was investigated. Firstly, the equilibrium states of theophylline were investigated. The data from gravimetric analysis at constant temperature and humidity were reported as desorption isotherms. The PXRD analysis was used to identify the different polymorphic forms of theophylline: the monohydrate, the metastable anhydrate, and the stable anhydrate. Solid-solid phase diagrams for two processing times were proposed. Secondly, the dehydration kinetics were studied. The water content evolutions with time were recorded at several temperatures from 20 degrees C to 80 degrees C and several relative humidities from 4% to 50%. Different mathematical models were used to fit the experimental data. The spatially averaged solution of 2D Fickian transient diffusion equation best represented the water mass loss versus time experimental relationship. The dehydration rate constant was found to increase exponentially with air temperature and to decrease exponentially with air relative humidity. PMID- 26556001 TI - Development and Evaluation of Dual Cross-Linked Pulsatile Beads for Chronotherapy of Rheumatoid Arthritis. AB - In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Lornoxicam dual cross-linked beads were prepared by dropping dispersed phase of lornoxicam, pectin, and sodium alginate into the dispersion phase of different concentrations of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1 : 2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5-8 h before release of lornoxicam from the formulated beads. Thus, formulated dual cross-linked beads when administered at bed time may release lornoxicam when needed most for chronotherapeutics of early morning rheumatoid arthritis attacks in chronic patients. PMID- 26556002 TI - Synthesis, Characterization, and Anti-Inflammatory Activity of Newer Quinazolinone Analogs. AB - A series of 3-[2'-(Substitutedbenzylideneamino)phenyl]-2-methyl-6-substituted quinazolin-4-ones (5-10), 3-[2'-(3(")-chloro-2(")-oxo-4(") substitutedphenylazetidin-1(")-yl)phenyl]-2-methyl-6-substitutedquinazolin-4-ones (11-16), and 3-[2'-(2(")-substitutedphenyl-4(")-oxo-1("),3(")-thiazolidin-3(") yl)phentl]-2-methyl-6-substitutedquinazolin-4-ones (17-22) have been synthesized in the present study. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, (1)H NMR, and mass spectral data. All the newly synthesized compounds were screened for anti-inflammatory and analgesic activities. PMID- 26556003 TI - Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl beta-Cyclodextrin Inclusion Complexes. AB - Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15-19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpbeta-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpbeta-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin. PMID- 26556004 TI - Using Ex Vivo Upright Droplet Cultures of Whole Fetal Organs to Study Developmental Processes during Mouse Organogenesis. AB - Investigating organogenesis in utero is a technically challenging process in placental mammals due to inaccessibility of reagents to embryos that develop within the uterus. A newly developed ex vivo upright droplet culture method provides an attractive alternative to studies performed in utero. The ex vivo droplet culture provides the ability to examine and manipulate cellular interactions and diverse signaling pathways through use of various blocking and activating compounds; additionally, the effects of various pharmacological reagents on the development of specific organs can be studied without unwanted side effects of systemic drug delivery in utero. As compared to other in vitro systems, the droplet culture not only allows for the ability to study three dimensional morphogenesis and cell-cell interactions, which cannot be reproduced in mammalian cell lines, but also requires significantly less reagents than other ex vivo and in vitro protocols. This paper demonstrates proper mouse fetal organ dissection and upright droplet culture techniques, followed by whole organ immunofluorescence to demonstrate the effectiveness of the method. The ex vivo droplet culture method allows the formation of organ architecture comparable to what is observed in vivo and can be utilized to study otherwise difficult-to study processes due to embryonic lethality in in vivo models. As a model application system, a small-molecule inhibitor will be utilized to probe the role of vascularization in testicular morphogenesis. This ex vivo droplet culture method is expandable to other fetal organ systems, such as lung and potentially others, although each organ must be extensively studied to determine any organ specific modifications to the protocol. This organ culture system provides flexibility in experimentation with fetal organs, and results obtained using this technique will help researchers gain insights into fetal development. PMID- 26556005 TI - Association Between Trabecular Meshwork Anteroposterior Length and Anterior Chamber Angle Width. AB - PURPOSE: To investigate the association between trabecular meshwork anteroposterior length and anterior chamber angle width in nonglaucomatous subjects. DESIGN: Prospective, cross-sectional study. METHODS: Time-domain and spectral-domain anterior segment optical coherence tomography images for 561 eyes from 366 nonglaucomatous subjects were analyzed to determine trabecular meshwork anteroposterior length and 3 anterior chamber angle width parameters measured at different distances from the scleral spur: angle opening distance at 250 MUm (AOD250), 500 MUm (AOD500), and 750 MUm (AOD750) from the scleral spur; trabecular-iris space area at 500 MUm (TISA500) and 750 MUm (TISA750) from the scleral spur; angle recess area at 750 MUm (ARA750) from the scleral spur. Univariable and multivariable linear mixed-effect regression models, the latter adjusting for age, sex, ethnicity, axial length, and the use of both eyes in the same subject, were used to evaluate the association between trabecular meshwork anteroposterior length and anterior chamber angle width parameters. RESULTS: Mean trabecular meshwork anteroposterior length was 824.86 +/- 181.77 MUm. Univariate regression analyses showed a significant positive association between trabecular meshwork anteroposterior length and all anterior chamber angle width parameters: AOD250 (P < .001; beta = 335.13), AOD500 (P < .001; beta = 271.84), AOD750 (P < .001; beta = 202.56), TISA500 (P < .001; beta = 780.78), TISA750 (P < .001; beta = 449.17), ARA750 (P < .001; beta = 381.39). Multivariate regression analyses showed a significant positive association between trabecular meshwork anteroposterior length and all anterior chamber angle width parameters: AOD250 (P = .005; beta = 294.02), AOD500 (P = .036; beta = 172.94), AOD750 (P = .049; beta = 125.58), TISA500 (P = .004; beta = 611.51), TISA750 (P = .011; beta = 333.96), ARA750 (P < .0001; beta = 309.12). CONCLUSIONS: Wider anterior chamber angle is associated with greater trabecular meshwork anteroposterior length. PMID- 26556006 TI - Fine Needle Aspiration Biopsy in Uveal Melanoma: Technique, Complications, and Outcomes. AB - PURPOSE: To report the technical aspects, complications, and outcomes concerning fine needle aspiration biopsy (FNAB) in uveal melanoma. DESIGN: Retrospective cohort study. METHODS: Patients with uveal melanoma who underwent transscleral or transvitreal FNAB at an ocular oncology center were retrospectively evaluated. FNAB was performed if the tumor was more than 5 mm in thickness. Array comparative genomic hybridization analysis was performed on biopsy samples with sufficient tissue. The main outcome measures were success (sample that gave a successful result for biomarker analysis) rate, complications, liver metastasis, and overall survival. RESULTS: There were 217 (114 male, 52%) consecutive study patients with a mean age of 56.7 (16-84) years. The mean follow-up period was 31 (range 3.6-61.3) months. Mean tumor thickness was 8.4 (range 5-12) mm. The overall success rate of the procedure was 169 patients (77.9%). Thirty-one patients (14.3%) experienced intravitreal hemorrhage, of whom 9 (4.1%) required vitreal surgery. There was no case of endophthalmitis, orbital dissemination, local recurrence, or rhegmatogenous retinal detachment. Thirty-two patients (14.7%) developed metastasis during the study, of whom 20 (9.2%) died. Of the 169 successful samples, 53 patients (31%) were classified as low risk, 41 (24%) as intermediate risk, and 54 (32%) as high risk. Fifteen patients (9%) did not have any detectable chromosomal abnormality and 6 (4%) could not be classified. CONCLUSION: FNAB is a relatively safe and successful technique that can be routinely used to obtain tissue for molecular genomic analysis; such analysis helps determine the diagnosis and prognosis in uveal melanoma. PMID- 26556007 TI - Conjunctival Primary Acquired Melanosis: Is It Time for a New Terminology? AB - PURPOSE: To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis." DESIGN: Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations. METHODS: Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia associated transcription factor (MiTF), and Ki-67 for calculating the proliferation index are illustrated. RESULTS: "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes. CONCLUSION: All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later surgery. PMID- 26556008 TI - Reliability of Pentacam HR Thickness Maps of the Entire Cornea in Normal, Post Laser In Situ Keratomileusis, and Keratoconus Eyes. AB - PURPOSE: To measure the repeatability and reproducibility of Pentacam HR system thickness maps for the entire cornea in normal, post-laser in situ keratomileusis (post-LASIK), and keratoconus (KC) eyes. DESIGN: Reliability study. METHODS: Sixty normal subjects (60 eyes), 30 post-LASIK subjects (60 eyes), and 14 KC patients (27 eyes) were imaged with the Pentacam HR system by 2 well-trained operators. For pachymetry the cornea was divided into 4 zones: a central zone (2 mm diameter) and concentric pericentral zone (2-5 mm), transitional zone (5-7 mm), and peripheral zone (7-10 mm). The 3 concentric zones were subdivided into 8 sectors. Intraobserver repeatability and interobserver reproducibility of entire corneal thickness maps were tested by the repeatability and reproducibility coefficients, intraclass correlation coefficients, coefficient of variation, and 95% limits of agreement. RESULTS: From central to peripheral zones, the precision of corneal thickness measurements became gradually smaller. Central zone repeatability and reproducibility were the best in the normal, post-LASIK, and KC groups. The peripheral superior sectors showed poorer repeatability and reproducibility for all subjects. The intraobserver repeatability and interobserver reproducibility for all zones were <=19.3 MUm, <=22.1 MUm, and <=20.7 MUm, in the normal, post-LASIK, and KC groups, respectively. The intraobserver and interobserver coefficients of variation for all zones were <=1.3%, <=1.6%, and <=1.6% for all 3 groups. CONCLUSIONS: Pentacam HR system pachymetry of the entire cornea provided good precision in normal, post-LASIK, and KC corneas. Thickness measurements in the peripheral cornea should be interpreted with caution in abnormal corneas after surgery or with diseases. PMID- 26556009 TI - Development and preliminary validation of an Observation List for detecting mental disorders and social Problems in the elderly in primary and home care (OLP). AB - OBJECTIVE: Even though the prevalence of mental disorders and social problems is high among elderly patients, it is difficult to detect these in a primary (home) care setting. Goal was the development and preliminary validation of a short observation list to detect six problem areas: anxiety, depression, cognition, suspicion, loneliness, and somatisation. METHODS: A draft list of indicators identified from a short review of the literature and the opinions of 22 experts was evaluated by general practitioners (GPs) and home care organisations for feasibility. It was then used by GPs and home care personnel to observe patients, who also completed validated tests for psychological disorders (General Health Questionnaire 12 item version (GHQ-12)), depression (Geriatric Depression Scale 15-item version (GDS-15)), anxiety and suspicion (Symptom Checklist-90 (SCL-90)), loneliness (University of California, Los Angeles (UCLA)), somatisation (Illness Attitude Scale (IAS)), and cognition (Mini-Mental State Examination (MMSE)). RESULTS: GPs and home care personnel observed 180 patients (mean age 78.4 years; 66% female) and evaluated the draft list during a regular visit. Cronbach's alpha was 0.87 for the draft list and >=0.80 for the draft problem areas (loneliness and suspicion excepted). Principal component analysis identified six components (cognition, depression + loneliness, somatisation, anxiety + suspicion, depression (other signs), and an ambiguous component). Convergent validity was shown for the indicators list as a whole (using the GHQ-12), and the subscales of depression, anxiety, loneliness, cognition, and somatisation. Using pre-set agreed criteria, the list was reduced to 14 final indicators divided over five problem areas. CONCLUSION: The Observation List for mental disorders and social Problems (OLP) proved to be preliminarily valid, reliable, and feasible for use in primary and home care settings. Copyright (c) John Wliey & Sons, Ltd. PMID- 26556010 TI - Collaborative treatment of huge intrathoracic meningoceles associated with neurofibromatosis type 1: a case report. AB - BACKGROUND: An intrathoracic meningocele is a relatively rare disease, and it commonly accompanies neurofibromatosis type 1. Patients tend to have no symptom but if its size is too large and compresses a lung and neighboring organs, it needs shunt drainage or surgical resection. CASE PRESENTATION: Herein, we present the case of a 52 year-old female patient with huge intrathoracic meningoceles associated with neurofibromatosis type 1, who has complained about chest discomfort and dyspnea at rest. As for a preliminary treatment, a neurosurgeon had performed a cystoperitoneal shunt, but the symptoms continued and the size of mass and the amount of pleural effusion did not change significantly. Therefore, the huge thoracic meningoceles were successfully treated through the thoracotomic approach in combination with lumbar puncture and cerebrospinal fluid drainage. CONCLUSIONS: It is reported that double huge intrathoracic meningoceles associated with neurofibromatosis type 1 was successfully treated by a shunting procedure followed by thoracotomic resection with collaboration of a neurosurgeon. PMID- 26556011 TI - MYB3Rs, plant homologs of Myb oncoproteins, control cell cycle-regulated transcription and form DREAM-like complexes. AB - Plant MYB3R transcription factors, homologous to Myb oncoproteins, regulate the genes expressed at G2 and M phases in the cell cycle. Recent studies showed that MYB3Rs constitute multiprotein complexes that may correspond to animal complexes known as DREAM or dREAM. Discovery of the putative homologous complex in plants uncovered their significant varieties in structure, function, dynamics, and heterogeneity, providing insight into conserved and diversified aspects of cell cycle-regulated gene transcription. PMID- 26556012 TI - Walking through doorways causes forgetting: Event structure or updating disruption? AB - According to event cognition theory, people segment experience into separate event models. One consequence of this segmentation is that when people transport objects from one location to another, memory is worse than if people move across a large location. In two experiments participants navigated through a virtual environment, and recognition memory was tested in either the presence or the absence of a location shift for objects that were recently interacted with (i.e., just picked up or set down). Of particular concern here is whether this location updating effect is due to (a) differences in retention intervals as a result of the navigation process, (b) a temporary disruption in cognitive processing that may occur as a result of the updating processes, or (c) a need to manage multiple event models, as has been suggested in prior research. Experiment 1 explored whether retention interval is driving this effect by recording travel times from the acquisition of an object and the probe time. The results revealed that travel times were similar, thereby rejecting a retention interval explanation. Experiment 2 explored whether a temporary disruption in processing is producing the effect by introducing a 3-second delay prior to the presentation of a memory probe. The pattern of results was not affected by adding a delay, thereby rejecting a temporary disruption account. These results are interpreted in the context of the event horizon model, which suggests that when there are multiple event models that contain common elements there is interference at retrieval, which compromises performance. PMID- 26556013 TI - The one and the many: the search for unity in nature. AB - The essence of physical reality-what the world consists of-has been a heated focus of contention for millennia. First with philosophers and then with physicists, the debate has been polarized since the beginning: while those loosely known as Platonists search for an underlying unity in nature, others caution that such unity is unachievable in practice and in principle. In this essay, we review both positions, arguing strongly for the latter in anticipation of experimental results from the Large Hadron Collider, the particle accelerator from the European Center for Nuclear Research. We further argue that, for the first time in history, the material essence of reality could be determined from an empirical standpoint as opposed to a purely dialectic one, settling the age old debate. PMID- 26556014 TI - Picrorhiza kurroa Inhibits Experimental Arthritis Through Inhibition of Pro inflammatory Cytokines, Angiogenesis and MMPs. AB - The present study investigates the anti-arthritic activity of Picrorhiza kurroa (PK), on formaldehyde and adjuvant-induced arthritis (AIA) in rat. Administration of Picrorhiza kurroa rhizome extract (PKRE) significantly inhibited joint inflammation in both animal models. In AIA-induced arthritic rat, treatment with PKRE considerably decreased synovial expression of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor receptor-1 (TNF-R1) and vascular endothelial growth factor as compared with control. The anti-arthritic activity was found to be well substantiated with significant suppression of oxidative and inflammatory markers as there was decreased malonaldehyde, Nitric oxide, tumor necrosis factor alpha levels accompanied with increased glutathione and superoxide dismutase, catalase activities. Additionally, PKRE significantly inhibited the expression of degrading enzymes, matrix metalloproteinases-3 and matrix metalloproteinases-9 in AIA-induced arthritic rat. Histopathology of paw tissue displayed decreased inflammatory cell infiltration as compared with control. Taken together, these results demonstrated the anti-arthritic activity of PKRE against experimental arthritis, and the underlying mechanism behind this efficacy might be mediated by inhibition of inflammatory mediators and angiogenesis, improvement of the synovium redox status and decreased expression of matrix metalloproteinases. PMID- 26556016 TI - Aggregating tags for column-free protein purification. AB - Protein purification remains a central need for biotechnology. In recent years, a class of aggregating tags has emerged, which offers a quick, cost-effective and column-free alternative for producing recombinant proteins (and also peptides) with yield and purity comparable to that of the popular His-tag. These column free tags induce the formation of aggregates (during or after expression) when fused to a target protein or peptide, and upon separation from soluble impurities, the target protein or peptide is subsequently released via a cleavage site. In this review, we categorize these tags as follows: (i) tags that induce inactive protein aggregates in vivo; (ii) tags that induce active protein aggregates in vivo; and (iii) tags that induce soluble expression in vivo, but aggregates in vitro. The respective advantages and disadvantages of these tags are discussed, and compared to the three conventional tags (His-tag, maltose binding protein [MBP] tag, and intein-mediated purification with a chitin-binding tag [IMPACT-CN]). While this new class of aggregating tags is promising, more systematic tests are required to further the use. It is conceivable, however, that the combination of these tags and the more traditional columns may significantly reduce the costs for resins and columns, particularly for the industrial scale. PMID- 26556015 TI - Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria. AB - INTRODUCTION: Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. AIM: This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. METHODS: Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. MAIN OUTCOME MEASURES: All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. RESULTS: At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 +/- 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 +/- 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 +/- 13.9) compared with when they had received only psychological support (60.9 +/- 12.2, P = 0.001). CONCLUSION: Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents. PMID- 26556017 TI - [Scapular fractures]. AB - Scapular fractures are still a challenge in traumatology of the musculoskeletal apparatus. Their proper understanding is impossible without fundamental anatomical and clinical knowledge. A considerable part of scapular fractures is associated with other severe injuries, particularly to the chest. Essential for diagnosis and treatment of these fractures is radiographic examination, primarily both Neer projections and 3D CT reconstructions. The classifications used so far should be revised as they do not reflect real types of these fractures. Operative treatment should be considered in displaced scapular fractures. Such treatment is not urgent as these fractures may be operated on within up to three weeks of the primary injury. Due to the fact that this is a severe but rare injury, they should be referred to specialized centres. KEY WORDS: scapular fractures classification of scapular fractures operative treatment of scapular fractures. PMID- 26556018 TI - [Kocher approach to the elbow and its options]. AB - The original Kocher approach was published several times in the 18921907 period. It extends in the interval between the extensor carpi ulnaris and the anconeus and consists in subperiostal release of the lateral collateral ligament (LCL), joint capsule and origin of extensors at the lateral epicondyle and their retraction anteriorly, and a similar release of the anconeus from the distal humerus and its reflection posteriorly. This provides an extensive approach to the elbow. Today this approach is described in the textbooks in various modifications that have little in common with the original description except for the fact that dissection is made in the so called Kocher interval between the extensor carpi ulnaris and the anconeus. Therefore it is often called a limited Kocher approach.The study describes our modification of the Kocher approach that we use primarily in fractures of the head and neck of the radius, in certain fractures of the distal humerus, and also in irreducible dislocations and certain fracture-dislocations of the elbow.The incision is made along the line connecting the lateral epicondyle of the humerus and the border between the proximal and middle thirds of the ulna. The incision is pulled open and the strong, white opalescent common extensor fascia incised in order to identify the interval between the extensor carpi ulnaris and the anconeus. The two muscles are separated by thin vascularized fatty connective tissue which is split in order to expose a typical tendon reinforcing the upper half of the anterior margin of the anconeus. In this phase it is beneficial to detach the origin of the extensor carpi ulnaris from the lateral epicondyle. It facilitates retraction of the extensor carpi ulnaris anteriorly and of the anconeus slightly posteriorly. In contrast with the original Kocher approach, we do not release the anconeus from the lateral epicondyle of the humerus.The muscles are retracted to expose the anterolateral surface of the joint capsule and to identify the course of the LCL complex. The capsule is incised along the anterior margin of LCL, starting from the lateral epicondyle up to and including the radial annular ligament. Arthrotomy performed anterior to LCL spares the insertion of the lateral ulnar collateral ligament on the ulna and, consequently, preserves the elbow stability. If dissection more distally is required in order to expose the radial neck, part of the supinator must be incised as well. In such case the forearm is first carefully pronated as much as possible, as a result of which the canalis supinatorius including the deep branch of the radial nerve will move anteriorly, thus reducing the risk of injury to the nerve.The capsule is incised and opened, revealing the anterolateral surface of the head of humerus and radial head. In this phase it is beneficial to flex the elbow to 90100 degrees, when the anterior part of the capsule will get flabby and allow a better visualization of the joint. The joint capsule must be released from the distal humerus together with extensors originating at the lateral epicondyle of humerus. This will considerably improve visualization of the anterior part of the joint cavity. During wound closure the common extensor fascia must be firmly sutured, as it is a significant but often underestimated stabilizer of the lateral part of the elbow.The extended option of the Kocher approach consists in retraction of the anconeus proximally. It is indicated in certain fracture-dislocations of the proximal forearm, i.e. fractures of the radial head and the entire proximal ulna. After dissection of the whole anconeus, this muscle is detached from the ulnar shaft and entirely reflected proximally. The muscle remains attached by its short proximal margin to the lateral epicondyle of humerus and to olecranon. This eliminates the risk of injury to the neurovascular hilus of the muscle, as the motoric nerve enters the muscle in the middle of its upper border. Retraction of the muscle exposes both the lateral surface of the joint capsule and the lateral surface of the proximal ulna. Further procedure, i.e. incision of the capsule and inspection of the joint, is the same as in the limited Kocher approach. PMID- 26556019 TI - [Approaches to radial shaft]. AB - In the clinical practice, radial shaft may be exposed via two approaches, namely the posterolateral Thompson and volar (anterior) Henry approaches. A feared complication of both of them is the injury to the deep branch of the radial nerve. No consensus has been reached, yet, as to which of the two approaches is more beneficial for the proximal half of radius. According to our anatomical studies and clinical experience, Thompson approach is safe only in fractures of the middle and distal thirds of the radial shaft, but highly risky in fractures of its proximal third. Henry approach may be used in any fracture of the radial shaft and provides a safe exposure of the entire lateral and anterior surfaces of the radius.The Henry approach has three phases. In the first phase, incision is made along the line connecting the biceps brachii tendon and the styloid process of radius. Care must be taken not to damage the lateral cutaneous nerve of forearm.In the second phase, fascia is incised and the brachioradialis identified by the typical transition from the muscle belly to tendon and the shape of the tendon. On the lateral side, the brachioradialis lines the space with the radial artery and veins and the superficial branch of the radial nerve running at its bottom. On the medial side, the space is defined by the pronator teres in the proximal part and the flexor carpi radialis in the distal part. The superficial branch of the radial nerve is retracted together with the brachioradialis laterally, and the radial artery medially.In the third phase, the attachment of the pronator teres is identified by its typical tendon in the middle of convexity of the lateral surface of the radial shaft. The proximal half of the radius must be exposed very carefully in order not to damage the deep branch of the radial nerve. Dissection starts at the insertion of the pronator teres and proceeds proximally along its lateral border in interval between this muscle and insertion of the supinator. During release and retraction of the supinator posterolaterally, it is beneficial to supinate the proximal fragment of the shaft as much as possible, preferably by K-wire drilled perpendicular into the anterior surface of the fragment and rotated externally. As a result, canalis supinatorius is moved posteriorly which reduces the risk of injury to the deep branch of the radial nerve. The supinator is released always from distal to proximal. Approximately at the level of the biceps brachii tendon, it is usually necessary to identify and ligate the radial recurrent artery and vein which prevent retraction of the radial vessels medially. After detachment of the whole supinator, a small Hohmann elevator is carefully inserted between the muscle and the bone. If necessary, it is now possible to open the anterior surface of the joint capsule and revise the humeroradial joint. PMID- 26556020 TI - [Internal fixation of radial shaft fractures: Anatomical and biomechanical principles]. AB - Radius is a critical bone for functioning of the forearm and therefore its reconstruction following fracture of its shaft must be anatomical in all planes and along all axes. The method of choice is plate fixation. However, it is still associated with a number of unnecessary complications that were not resolved even by introduction of locking plates, but rather the opposite. All the more it is surprising that discussions about anatomical and biomechanical principles of plate fixation have been reduced to minimum or even neglected in the current literature. This applies primarily to the choice of the surgical approach, type of plate, site of its placement and contouring, its working length, number of screws and their distribution in the plate. At the same time it has to be taken into account that a plate used to fix radius is exposed to both bending and torsion stress. Based on our 30-year experience and analysis of literature we present our opinions on plate fixation of radial shaft fractures:We always prefer the volar Henry approach as it allows expose almost the whole of radius, with a minimal risk of injury to the deep branch of the radial nerve.The available studies have not so far found any substantial advantage of LCP plates as compared to 3.5mm DCP or 3.5mm LC DCP plates, quite the contrary. The reason is high rigidity of the locking plates, a determined trajectory of locking screws which is often unsuitable, mainly in plates placed on the anterior surface of the shaft, and failure to respect the physiological curvature of the radius. Therefore based on our experience we prefer "classical" 3.5mm DCP plates.Volar placement of the plate, LCP in particular, is associated with a number of problems. The volar surface covered almost entirely by muscles, must be fully exposed which negatively affects blood supply to the bone. A straight plate, if longer, either lies with its central part partially off the bone and overlaps the interosseous border, or its ends overhang the bone laterally. In a locking plate with a fixed determined trajectory of screws, the locking screws in the central holes of the plate pass off the shaft centre only through a thin interosseous border (medial position), or screws at the ends of the plate are inserted eccentrically (lateral position). Both these techniques reduce stability of internal fixation. Where the plate overlaps the interosseous border, it is difficult to control the mutual rotation of the two main fragments. A shorter LCP plate increases rigidity of fixation, suppresses bone healing and often leads to non-union.Placement of the plate on the lateral surface of the radius is more beneficial from the viewpoint of the bending and torsion stress. Lateral surface of the radius is a tension site, its distal half is not covered by muscles which eliminates the necessity to release them, the interosseous border is not obscured by plate and all this allows a safe control of rotational position of fragments. A properly pre-bent plate follows the physiological curvature of the lateral surface of the radius. Full tightening of standard screws will fix both main fragments firmly to the apex of plate concavity and increase stability of the internal fixation. Due to the shape of the cross-section of the radial shaft, the trajectory of screws is the longest in case of lateral placement of the plate, which increases rotational stability.We place the plate always in a minimal three hole length on each main fragment. Transverse two-fragment fractures may be fixed with a 2+2 configuration, i.e. with two screws on each main fragment. Fractures with an inter-fragment or comminuted zone are fixed in the 3+3 mode. More extensive comminutions, defects or segmental fractures require 4 plate holes on each fragment, but not more. When drilling screw holes the drill must be directed into the interosseous border. As a result, the screw has the longest trajectory and the best fixation in the bone. Perforation of the anterior or posterior surface of the radius considerably shortens the trajectory of the screw and thus reduces stability of internal fixation. PMID- 26556021 TI - [Surgical treatment of acromioclavicular dislocation: Tension band wiring versus hook plate]. AB - INTRODUCTION: The aim of the prospective randomized study was to compare tension wire cerclage and hook plate in the treatment of AC dislocation, primarily from the viewpoint of functional and radiological results. METHOD: The cohort comprised 80 patients with acute acromioclavicular (AC) dislocation of types 3, 4 and 5 of Rockwood classification. The diagnosis was based on the clinical (disfiguration and instability) and radiographic examination (AP and stress radiograph). Forty patients were treated with tension band wiring (TBW) and another 40 with a hook plate (HP). Evaluation was performed during one year after the surgery based on radiographs and the Constant score. RESULTS: The mean Constant score 3 months after the surgery was 84 points for TBW and 88 points for HP. One year after the surgery, the result was the same in both groups: 93 points. In HP group the score increased from 56 to 78 points between 2 and 4 weeks from the surgery. In 71 cases the postoperative position of the AC joint and implant was assessed as correct. Malposition of Kirschner wires was recorded in 6 cases and horizontal widening of the AC joint in 3 cases. Redislocation of up to 50100% of the width of acromion was shown by radiograph in 4 TBW patients (10%) and in 5 HP patients (13%). A visible osteolysis of the distal surface of acromion was found in 83% of patients with HP. Complications were recorded in 30% of TBW patients and in 5% of HP patients. CONCLUSION: Based on radiological and clinical results assessed 3 months and 1 year after the surger, the hook plate and tension band wiring are comparable treatment methods for AC dislocation. The hook plate is associated with a lower complication rate and allows earlier full weight bearing and mobility than tension wire cerclage. In TBW we recommend to remove the implant after 8 weeks; 6 weeks are in our view too short a period for the healing of soft tissues. In HP it is suitable to remove the hardware by 3 months due to potential subacromial irritation and pressure-induced osteolysis. PMID- 26556022 TI - Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore. AB - BACKGROUND: Brain injury is an important, potentially devastating, complication in cardiac surgery. A significant number of patients suffer perioperative complications involving the central nervous system. Clinical manifestations of brain injury are associated with significantly increased mortality, morbidity and health resource utilization. Serum biomarkers have been studied in cardiac surgery to measure the degree and incidence of brain injury and to improve patient management. METHODS: All relevant studies were identified by computerized searches of PubMed using the following Medical Subject Headings and keywords term: biomarker, cardiac surgery, brain injury and neurological complication. RESULTS: The biomarkers that appear to be better indicators of brain injury severity in cardiac surgery and its consequences are S100B protein, neuron specific enolase, glial fibrillary acidic protein, tau protein, matrix metalloproteinase-9, ubiquitin C terminal hydroxylase-L1 and neurofilaments. CONCLUSIONS: These biomarkers, independently of clinical and radiological findings, show global cerebral situation at the cellular level and the degree of brain dysfunction. However, up to date, there is no biomarker entirely suitable for the detection of brain injury after cardiac surgery. PMID- 26556023 TI - A Sensitive Electrochemiluminescence Immunosensor for Celiac Disease Diagnosis Based on Nanoelectrode Ensembles. AB - We report here the design of a novel immunosensor and its application for celiac disease diagnosis, based on an electrogenerated chemiluminescence (ECL) readout, using membrane-templated gold nanoelectrode ensembles (NEEs) as a detection platform. An original sensing strategy is presented by segregating spatially the initial electrochemical reaction and the location of the immobilized biomolecules where ECL is finally emitted. The recognition scaffold is the following: tissue transglutaminase (tTG) is immobilized as a capturing agent on the polycarbonate (PC) surface of the track-etched templating membrane. It captures the target tissue transglutaminase antibody (anti-tTG), and finally allows the immobilization of a streptavidin-modified ruthenium-based ECL label via reaction with a suitable biotinylated secondary antibody. The application of an oxidizing potential in a tri-n-propylamine (TPrA) solution generates an intense and sharp ECL signal, suitable for analytical purposes. Voltammetric and ECL analyses evidenced that the ruthenium complex is not oxidized directly at the surface of the nanoelectrodes; instead ECL is generated following the TPrA oxidation, which produces the TPrA*+ and TPrA* radicals. With NEEs operating under total overlap diffusion conditions, high local fluxes of these reactive radicals are produced by the nanoelectrodes in the immediate vicinity of the ECL labels, so that they efficiently generate the ECL signal. The radicals can diffuse over short distances and react with the Ru(bpy)32+ label. In addition, the ECL emission is obtained by applying a potential of 0.88 V versus Ag/AgCl, which is about 0.3 V lower than when ECL is initiated by the electrochemical oxidation of Ru(bpy)3(2+). The immunosensor provides ECL signals which scale with anti-tTG concentration with a linearity range between 1.5 ng.mL-1 and 10 MUg.mL-1 and a detection limit of 0.5 ng.mL-1. The sensor is finally applied to the analysis of anti-tTG in human serum samples, showing to be suitable to discriminate between healthy and celiac patients. PMID- 26556024 TI - Innate immune memory via ATF7-dependent epigenetic changes. PMID- 26556025 TI - Multiphysics Modeling of Microwave Heating of a Frozen Heterogeneous Meal Rotating on a Turntable. AB - A 3-dimensional (3-D) multiphysics model was developed to understand the microwave heating process of a real heterogeneous food, multilayered frozen lasagna. Near-perfect 3-D geometries of food package and microwave oven were used. A multiphase porous media model combining the electromagnetic heat source with heat and mass transfer, and incorporating phase change of melting and evaporation was included in finite element model. Discrete rotation of food on the turntable was incorporated. The model simulated for 6 min of microwave cooking of a 450 g frozen lasagna kept at the center of the rotating turntable in a 1200 W domestic oven. Temperature-dependent dielectric and thermal properties of lasagna ingredients were measured and provided as inputs to the model. Simulated temperature profiles were compared with experimental temperature profiles obtained using a thermal imaging camera and fiber-optic sensors. The total moisture loss in lasagna was predicted and compared with the experimental moisture loss during cooking. The simulated spatial temperature patterns predicted at the top layer was in good agreement with the corresponding patterns observed in thermal images. Predicted point temperature profiles at 6 different locations within the meal were compared with experimental temperature profiles and root mean square error (RMSE) values ranged from 6.6 to 20.0 degrees C. The predicted total moisture loss matched well with an RMSE value of 0.54 g. Different layers of food components showed considerably different heating performance. Food product developers can use this model for designing food products by understanding the effect of thickness and order of each layer, and material properties of each layer, and packaging shape on cooking performance. PMID- 26556026 TI - Urinary system obstruction in a preterm infant: Questions. PMID- 26556027 TI - Urinary system obstruction in a preterm infant: Answers. PMID- 26556029 TI - Sequence-independent amplification coupled with DNA microarray analysis for detection and genotyping of noroviruses. AB - Noroviruses (NoVs) have high levels of genetic sequence diversities, which lead to difficulties in designing robust universal primers to efficiently amplify specific viral genomes for molecular analysis. We here described the practicality of sequence-independent amplification combined with DNA microarray analysis for simultaneous detection and genotyping of human NoVs in fecal specimens. We showed that single primer isothermal linear amplification (Ribo-SPIA) of genogroup I (GI) and genogroup II (GII) NoVs could be run through the same amplification protocol without the need to design and use any virus-specific primers. Related virus could be subtyped by the unique pattern of hybridization with the amplified product to the microarray. By testing 22 clinical fecal specimens obtained from acute gastroenteritis cases as blinded samples, 2 were GI positive and 18 were GII positive as well as 2 negative for NoVs. A NoV GII positive specimen was also identified as having co-occurrence of hepatitis A virus. The study showed that there was 100 % concordance for positive NoV detection at genogroup level between the results of Ribo-SPIA/microarray and the phylogenetic analysis of viral sequences of the capsid gene. In addition, 85 % genotype agreement was observed for the new assay compared to the results of phylogenetic analysis. PMID- 26556031 TI - Simvastatin inhibits oxidative stress via the activation of nuclear factor erythroid 2-related factor 2 signaling in trophoblast cells. AB - AIM: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator against oxidative stress through the induction of antioxidant and cytoprotective genes, such as heme oxygenase 1 (HO-1), glutamyl cysteine ligase catalytic (GCLC), and glutamyl cysteine ligase modulatory (GCLM). Nrf2 signaling is disrupted in pre-eclamptic placentas, although increased oxidative stress is implicated in pre-eclampsia. The aims of the study were: (i) to investigate the mechanism that underlies the impaired Nrf2 signaling in pre-eclamptic placentas, and (ii) to examine the potential therapeutic role of statin for pre-eclampsia. MATERIAL AND METHODS: Human choriocarcinoma JAR cells were cultured under normoxia (20% O2 ) or hypoxia (1% O2 ). Small-interfering ribonucleic acids were used to knockdown Nrf2. Real-time quantitative reverse transcriptase polymerase chain reaction and Western blotting were used to evaluate the influence of oxidative stress (H2O2 100 MUM) and simvastatin (50 MUM) on Nrf2 and its target genes. Reactive oxygen species levels were analyzed by flow cytometry in immortalized human trophoblast TCL1 cells treated with or without H2O2 (100 MUM) +/- simvastatin (50 MUM). RESULTS: Nuclear factor erythroid 2-related factor 2 activation was significantly suppressed under hypoxic conditions. Nrf2 knockdown resulted in insufficient enhancement of HO-1, GCLC and GCLM expression under oxidative stress. In contrast, Nrf2 signaling was augmented by simvastatin, which suppressed the induction of oxidative stress in trophoblasts. CONCLUSION: Hypoxia is one of the important negative regulators of Nrf2 activation, and simvastatin inhibits oxidative stress through the activation of Nrf2 signaling in trophoblasts, indicating the potential therapeutic role of statin for pre eclampsia. PMID- 26556028 TI - The non-immunosuppressive management of childhood nephrotic syndrome. AB - Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases found in the paediatric population and is associated with significant complications, including infection and thrombosis. A high proportion of children enter sustained remission before adulthood, and therapy must therefore mitigate the childhood complications, while minimising the long-term risk to health. Here we address the main complications of INS and summarise the available evidence and guidance to aid the clinician in determining the appropriate treatment for children with INS under their care. Additionally, we highlight areas where no consensus regarding appropriate management has been reached. In this review, we detail the reasons why routine prophylactic antimicrobial and antithrombotic therapy are not warranted in INS and emphasise the conservative management of oedema. When pharmacological intervention is required for the treatment of oedema, we provide guidance to aid the clinician in determining the appropriate therapy. Additionally, we discuss obesity and growth, fracture risk, dyslipidaemia and thyroid dysfunction associated with INS. Where appropriate, we describe how recent developments in research have identified potential novel therapeutic targets. PMID- 26556030 TI - High-level fed-batch fermentative expression of an engineered Staphylococcal protein A based ligand in E. coli: purification and characterization. AB - The major platform for high level recombinant protein production is based on genetically modified microorganisms like Escherichia coli (E. coli) due to its short dividing time, ability to use inexpensive substrates and additionally, its genetics is comparatively simple, well characterized and can be manipulated easily. Here, we investigated the possibilities of finding the best media for high cell density fermentation, by analyzing different media samples, focusing on improving fermentation techniques and recombinant protein production. Initial fermentation of E. coli BL21 DE3:pAV01 in baffled flasks showed that high cell density was achieved when using complex media, Luria-Bertani (LB) and Terrific medium broth (TB) (10 and 14 g/L wet weight, respectively), as compared to mineral media M9, modified minimal medium (MMM) and Riesenberg mineral medium (RM) (7, 8 and 7 g/L, respectively). However, in fed-batch fermentation processes when using MMM after 25 h cultivation, it was possible to yield an optical density (OD600) of 139 corresponding to 172 g/L of wet biomass was produced in a 30 L TV Techfors-S Infors HT fermenter, with a computer controlled nutrient supply (glucose as a carbon source) delivery system, indicating nearly 1.5 times that obtained from TB. Upon purification, a total of 1.65 mg/g of protein per gram cell biomass was obtained and the purified AviPure showed affinity for immunoglobulin. High cell density fed batch fermentation was achieved by selecting the best media and growth conditions, by utilizing a number of fermentation parameters like media, fermentation conditions, chemical concentrations, pO2 level, stirrer speed, pH level and feed media addition. It is possible to reach cell densities higher than shake flasks and stirred tank reactors with the improved oxygen transfer rate and feed. PMID- 26556032 TI - Comparison of methods for recruiting and engaging parents in online interventions: study protocol for the Cry Baby infant sleep and settling program. AB - BACKGROUND: Anticipatory guidance around the management of sleep and crying problems in early infancy has been shown to improve both infant behaviour and parent symptoms of postnatal depression. Digital technology offers platforms for making such programs widely available in a cost-efficient manner. However, it remains unclear who accesses online parenting advice and in particular, whether the parents who would most benefit are represented amongst users. It is also unknown whether the uptake of online programs can be improved by health professional recommendations, or whether parents require additional prompts and reminders to use the program. In this study we aim to: (1) determine whether weekly email prompts increase engagement with and use of a brief online program about infant sleeping and crying, (2) determine whether encouragement from a maternal and child health nurse promotes greater engagement with and use of the program, (3) examine who uses a brief online program about infant sleeping and crying; and, (4) examine the psychosocial characteristics of participants. METHODS/DESIGN: This study is a randomised, parallel group, superiority trial, with all participating primary carers of infants aged 2 to 12 weeks, receiving access to the online program. Two modes of recruitment will be compared: recruitment via an online notice published on a non-commercial, highly credible and evidence-based website for parents and carers and via the parent's Maternal and Child Health nurse. After baseline assessment, parents will be randomised to one of two support conditions: online program alone or online program plus weekly email prompts. Follow up data will be collected at 4 months of infant age. DISCUSSION: Results from this trial will indicate whether involvement from a health professional, and/or ongoing email contact is necessary to engage parents in a brief online intervention, and promote parental use of strategies suggested within the program. Results of this trial will inform the development of recruitment and engagement strategies for other online interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001098729. Registered 01 October 2013. PMID- 26556033 TI - Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2Rgammac(null) Mouse Brain Atlas. AB - Strain specific mouse brain magnetic resonance imaging (MRI) atlases provide coordinate space linked anatomical registration. This allows longitudinal quantitative analyses of neuroanatomical volumes and imaging metrics for assessing the role played by aging and disease to the central nervous system. As NOD/scid-IL-2Rgamma(c)(null) (NSG) mice allow human cell transplantation to study human disease, these animals are used to assess brain morphology. Manganese enhanced MRI (MEMRI) improves contrasts amongst brain components and as such can greatly help identifying a broad number of structures on MRI. To this end, NSG adult mouse brains were imaged in vivo on a 7.0 Tesla MR scanner at an isotropic resolution of 100 MUm. A population averaged brain of 19 mice was generated using an iterative alignment algorithm. MEMRI provided sufficient contrast permitting 41 brain structures to be manually labeled. Volumes of 7 humanized mice brain structures were measured by atlas-based segmentation and compared against non humanized controls. The humanized NSG mice brain volumes were smaller than controls (p < 0.001). Many brain structures of humanized mice were significantly smaller than controls. We posit that the irradiation and cell grafting involved in the creation of humanized mice were responsible for the morphological differences. Six NSG mice without MnCl2 administration were scanned with high resolution T2-weighted MRI and segmented to test broad utility of the atlas. PMID- 26556034 TI - Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice. AB - Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.p.) or IFN-beta (2000 IU, s.c.) was administered daily once a day or every other day, respectively, starting at disease onset, which differ among EAE mice between 11 and 15 days postinduction. Histological and immunohistochemistry (anti-Mac-3, anti-CD3 and anti-APP) assessments were performed in spinal cord in the postinduction time. Global gene expression in the brain was analyzed with the Illumina Mouse WG-6_V2 BeadChip microarray and the expression of particular genes, assessed by qPCR using the Fast SYBR Green RT-PCR Master Mix. Oxidative stress parameters (malondialdehyde, peroxidation potential, CAT/SOD ratio and GSH) were determined spectrophoto-metrically. Results showed that C-Pc ameliorates the clinical deterioration of animals, an effect that expresses the reduction of the inflammatory infiltrates invading the spinal cord tissue, the axonal preservation and the down-regulation of IL-17 expression in brain tissue and serum. C-Pc and IFN-beta improved the redox status in mice subjected to EAE, while microarray analysis showed that both treatments shared a common subset of differentially expressed genes, although they also differentially modulated another subset of genes. Specifically, C-Pc mainly modulated the expression of genes related to remyelination, gliogenesis and axon glia processes. Taken together, our results indicate that C-Pc has significant therapeutic effects against EAE, mediated by the dynamic regulation of multiple biological processes. PMID- 26556035 TI - TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers. AB - Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient. PMID- 26556036 TI - Patient Satisfaction with Methadone Maintenance Treatment in Vietnam: A Comparison of Different Integrative-Service Delivery Models. AB - BACKGROUND: Patient satisfaction is an important component of quality in healthcare delivery. To inform the expansion of Methadone Maintenance Treatment (MMT) services in Vietnam, we examined the satisfaction of patients with regards to different services delivery models and identified its associated factors. METHODS: We interviewed 1,016 MMT patients at 5 clinics in Hanoi and Nam Dinh province. The modified SATIS instrument, a 10-item scale, was used to measure three dimensions: "Services quality and convenience", "Health workers' capacity and responsiveness" and "Inter-professional care". RESULTS: The average score was high across three SATIS dimensions. However, only one third of patients completely satisfied with general health services and treatment outcomes. Older age, higher education, having any problem in self-care and anxiety/depression were negatively associated with patient's satisfaction. Meanwhile, patients receiving MMT at clinics, where more comprehensive HIV and general health care services were available, were more likely to report a complete satisfaction. CONCLUSION: Patients were highly satisfied with MMT services in Vietnam. However, treatment for drug users should go beyond methadone maintenance to address complicated health demands of drug users. Integrating MMT with comprehensive HIV and general health services together with improving the capacity of health workers and efficiency of services organisation to provide interconnected health care for drug users are critical for improving the outcomes of the MMT program. PMID- 26556037 TI - Dissociated rapid eye movement sleep dream experiences in type 1 narcolepsy: a case report. PMID- 26556039 TI - Correlation between neurochemical metabolism and memory function in adolescent patients with depression: A multi-voxel 1H magnetic resonance spectroscopy study. AB - AIMS: We utilized multi-voxel proton magnetic resonance spectroscopy ((1)H-MRS) to detect biochemical abnormalities in dorsolateral prefrontal white matter and anterior cingulate gray matter and to determine the correlation of biochemical changes with memory function in depressed adolescents. METHODS: A total of 24 depressed patients and 23 healthy controls were enrolled in this study. MRS was performed to assess the N-acetylaspartate (NAA)/creatine Cr and choline (Cho)/Cr ratios in dorsolateral prefrontal white matter and anterior cingulate gray matter of participants. Memory function was measured on the basis of Wechsler Memory Scale scores, and depression was diagnosed on the basis of clinical observation, interview, and Hamilton Depression Rating Scale scores. RESULTS: Compared with controls, depressed patients had significantly lower NAA/Cr and Cho/Cr ratios in left dorsolateral prefrontal white matter and lower NAA/Cr ratios in right dorsolateral prefrontal white matter (P < 0.05). No biochemical differences were identified in the bilateral anterior cingulate gray matter between the two groups. Nevertheless, the depressed patients showed significantly lower memory quotient than controls (P < 0.05). The NAA/Cr ratio in dorsolateral prefrontal white matter positively correlated with memory quotient (left: P < 0.01; right: P < 0.05). CONCLUSIONS: These findings suggest that biochemical abnormalities in prefrontal white matter are involved in the pathophysiology of adolescent depression. In particular, such abnormalities are already present at the early stage of the disorder, and low NAA/Cr in bilateral anterior frontal white matter may be associated with memory impairment and related neuropathology. PMID- 26556040 TI - Factors contributing to the treatment duration of diphenylcyclopropenone immunotherapy for periungual warts. AB - Diphenylcyclopropenone (DPCP) immunotherapy has been shown to be efficacious for the treatment of warts, especially periungual warts for which destructive techniques are limited. However, factors affecting the duration of treatment of periungual warts have not been studied. A total of 61 patients with periungual warts who were completely cured with DPCP immunotherapy were included in this study. Age, sex, disease duration, location (fingernail, toenail, or both), number of warts, diameter of the largest wart, application number for sensitization and two types of sensitization reactions, erythema and blister index (EBI), and pruritus index were evaluated. Multiple linear regression analysis was performed to find correlations of these variables with the treatment duration. Of the nine variables, application number for sensitization (regression coefficient = 3.251 and 2.428, respectively) and EBI (regression coefficient = 9.950 and -9.694, respectively) were independent factors significantly affecting both the total duration of treatment and the duration of treatment after sensitization (p < 0.05, respectively). The sample size was limited. A shorter sensitization period and more severe EBI of the sensitization reaction contribute to a shorter time required for a complete cure in the treatment of periungual warts with DPCP immunotherapy. PMID- 26556038 TI - Two alternative pathways for generating transmissible prion disease de novo. AB - INTRODUCTION: Previous studies established that prion disease with unique strain specific phenotypes could be induced by in vitro-formed recombinant PrP (rPrP) fibrils with structures different from that of authentic prions, or PrP(Sc). To explain the etiology of prion diseases, new mechanism proposed that in animals the transition from rPrP fibrils to PrP(Sc) consists of two main steps: the first involves fibril-induced formation of atypical PrPres, a self-replicating but clinically silent state, and the second consists of atypical PrPres-dependent formation of PrP(Sc) via rare deformed templating events. RESULTS: In the current study, atypical PrPres with characteristics similar to those of brain-derived atypical PrPres was generated in vitro. Upon inoculation into animals, in vitro generated atypical PrPres gave rise to PrP(Sc) and prion disease with a phenotype similar to those induced by rPrP fibrils. Significant differences in the sialylation pattern between atypical PrPres and PrP(Sc) suggested that only a small sub-fraction of the PrP(C) that is acceptable as a substrate for PrP(Sc) could be also recruited by atypical PrPres. This can explain why atypical PrPres replicates slower than PrP(Sc) and why PrP(Sc) outcompetes atypical PrPres. CONCLUSIONS: This study illustrates that transmissible prion diseases with very similar disease phenotypes could be produced via two alternative procedures: direct inoculation of recombinant PrP amyloid fibrils or in vitro-produced atypical PrPres. Moreover, this work showed that preparations of atypical PrPres free of PrP(Sc) can give rise to transmissible diseases in wild type animals and that atypical PrPres generated in vitro is an adequate model for brain-derived atypical PrPres. PMID- 26556041 TI - TLR7 Gln11Leu single nucleotide polymorphism and response to treatment with imiquimod in patients with basal cell carcinoma: a pilot study. AB - AIM: The Toll-like receptor 7 (TLR7) agonist, imiquimod, offers a topical and noninvasive therapeutic method for the clinical treatment of superficial basal cell carcinoma (BCC). In this study we explored the relationship between the functional X-linked TLR7 rs179008/Gln11Leu polymorphism and the response to imiquimod in patients with BCC. PATIENTS & METHODS: Thirty-four BCC patients treated with imiquimod were included in the study. SNP genotyping of the TLR7 promoter polymorphism was performed by TaqMan allelic discrimination assay. RESULTS: In the group of female nonresponders to imiquimod a higher frequency of the altered genotype compared with responders was observed. Similarly, in the group of male nonresponders to imiquimod both patients with the mutated genotype were nonresponders. CONCLUSION: The results of this study show that patients carrying at least one T allele of the TLR7 promoter polymorphism are associated with an increased probability to be resistant to imiquimod therapy. PMID- 26556042 TI - Species identification of dermatophytes in paraffin-embedded biopsies with a new polymerase chain reaction assay targeting the internal transcribed spacer 2 region and comparison with histopathological features. AB - BACKGROUND: Dermatophytosis is a very common skin infection with a broad clinical spectrum. Biopsies are often used to confirm the diagnosis, especially when the clinical presentation is unusual. Not uncommonly, organisms are hard to find even with periodic acid-Schiff stains. Polymerase chain reaction (PCR) for dermatophytes can be used in such cases. OBJECTIVES: To test a new PCR assay allowing species identification of dermatophytes on paraffin-embedded biopsies, and to reassess histopathological criteria for diagnosis of dermatophytosis. METHODS: In total, 121 biopsies of 92 patients with clinical suspicion of tinea were included. In 42 samples the clinical diagnosis had been confirmed histopathologically, and in 79 no fungal elements had been identified. PCRs targeting the internal transcribed spacer (ITS)2 region of dermatophytes were performed on the biopsies with subsequent sequencing. Sections were reassessed for the presence/absence of hyphae/spores, pattern and composition of infiltrate, and epidermal/follicular changes. Patient charts were reviewed for clinical data. RESULTS: The new ITS2 PCR assay detected 94% of the dermatophyte infections (compared with 79% identified by microscopy). Trichophyton rubrum was the dominant species (89%), and other species identified were Trichophyton verrucosum (2%), Microsporum canis (4%), Epidermophyton floccosum (2%) and Trichophyton interdigitale (4%). In particular, infections with T. interdigitale and manifestations with prominent spongiosis were not diagnosed histologically. Intracorneal neutrophils, which have been emphasized as a histopathological clue to dermatophytosis, were present in only 46% of PCR-positive samples. CONCLUSIONS: Molecular species identification of dermatophytes via ITS2 PCR can easily be implemented in a routine dermatopathology setting. It is fast and highly specific and improves the sensitivity of histopathological diagnosis of dermatophytosis. PMID- 26556043 TI - Concentration Determination of Copper in Aqueous Solution Using Deposition Assisted Laser-Induced Breakdown Spectroscopy (LIBS). AB - In this paper, by means of Cu(2+) converting to Cu, the sub-ppb detection of copper in aqueous solution was successfully achieved using laser-induced breakdown spectroscopy (LIBS), and the sensitivity was found depending on the voltage applied for the deposition. With increasing voltage, the minimum detectable concentration was significantly lowered, while the signal intensity instability was increased. In order to reduce the impact from the intensity fluctuation, an estimation method was developed to determine the copper concentration via comparing minimum detectable concentrations. The obtained results suggest this method is a potential way toward quantitative analysis. PMID- 26556044 TI - A Farm to Fork Risk Assessment for the Use of Wastewater in Agriculture in Accra, Ghana. AB - The need to minimise consumer risk, especially for food that can be consumed uncooked, is a continuing public health concern, particularly in places where safe sanitation and hygienic practices are absent. The use of wastewater in agriculture has been associated with disease risks, though its relative significance in disease transmission remains unclear. This study aimed at identifying key risk factors for produce contamination at different entry points of the food chain. Over 500 produce and ready-to-eat salad samples were collected from fields, markets, and kitchens during the dry and wet seasons in Accra, Ghana, and over 300 soil and irrigation water samples were collected. All samples were analysed for E. coli, human adenovirus and norovirus using standard microbiological procedures, and real time RT-PCR. Finally, critical exposures associated with microbial quality of produce were assessed through observations and interviews. The study found that over 80% of produce samples were contaminated with E. coli, with median concentrations ranging from 0.64 to 3.84 Log E. coli/g produce. Prepared salad from street food vendors was found to be the most contaminated (4.23 Log E. coli/g), and that consumption of salad exceeded acceptable health limits. Key risk factors identified for produce contamination were irrigation water and soil at the farm level. Storage duration and temperature of produce had a significant influence on the quality of produce sold at markets, while observations revealed that the washed water used to rinse produce before sale was dirty. The source of produce and operating with a hygiene permit were found to influence salad microbial quality at kitchens. This study argues for a need to manage produce risk factors at all domains along the food chain, though it would be more effective to prioritise at markets and kitchens due to cost, ease of implementation and public health significance. PMID- 26556045 TI - Outcomes and Diagnostic Processes in Outpatients with Presumptive Tuberculosis in Zomba District, Malawi. AB - BACKGROUND: In Malawi, outpatients who have presumptive tuberculosis (TB), i.e. fever, night sweats, weight loss and/or any-duration cough (HIV-infected) or cough of at least 2 weeks (HIV-uninfected), are registered in chronic cough registers. They should receive a diagnostic work-up with first-step provider initiated HIV testing and sputum testing which includes XpertMTB/RIF, following a national algorithm introduced in 2012. METHODS: An operational study, in which we prospectively studied 6-month outcomes of adult outpatients who were registered in chronic cough registers in Zomba Central Hospital and Matawale peri-urban Health Center, between February and September 2013. We recorded implementation of the diagnostic protocol and outcomes at 6 months from registration. RESULTS: Of 348 patients enrolled, 165(47%) were male, median age was 40 years, 72(21%) had previous TB. At registration 154(44%) were known HIV-positive, 34(10%) HIV negative (26 unconfirmed) and 160(46%) had unknown HIV status; 104(56%) patients with unknown/unconfirmed HIV status underwent HIV testing. At 6 months 191(55%) were HIV-positive, 87(25%) HIV-negative (26 unconfirmed) and 70(20%) still had unknown HIV status. Higher age and registration in Matawale were independently associated with remaining unknown HIV status after 6 months. 62% of patients had sputum tested, including XpertMTB/RIF, according to the algorithm. TB was diagnosed in 54(15%) patients. This was based on XpertMTB/RIF results in 8(15%) diagnosed cases. In 26(48%) TB was diagnosed on clinical grounds. Coverage of ART in HIV-positive patients was 89%. At 6 months, 236(68%) were asymptomatic, 48(14%) symptomatic, 25(7%) had been lost-to-follow-up and 39(11%) had died. Mortality among those HIV-positive, HIV-negative and with unknown HIV-status was 15%, 2% and 10%, respectively. Male gender, being HIV-positive-not-on-ART and not receiving antibiotics were independent risk factors for mortality. CONCLUSION: HIV prevalence among patients with presumptive TB was high (55%). One quarter was not HIV tested and mortality in this group was substantial (10%). The impact of XpertMTB/RIF on TB diagnosis was limited. PMID- 26556047 TI - Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis. AB - Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low alpha-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes. PMID- 26556046 TI - The Effect of Acute and Chronic Social Stress on the Hippocampal Transcriptome in Mice. AB - Psychogenic stress contributes to the formation of brain pathology. Using gene expression microarrays, we analyzed the hippocampal transcriptome of mice subjected to acute and chronic social stress of different duration. The longest period of social stress altered the expression of the highest number of genes and most of the stress-induced changes in transcription were reversible after 5 days of rest. Chronic stress affected genes involved in the functioning of the vascular system (Alas2, Hbb-b1, Hba-a2, Hba-a1), injury response (Vwf, Mgp, Cfh, Fbln5, Col3a1, Ctgf) and inflammation (S100a8, S100a9, Ctla2a, Ctla2b, Lcn2, Lrg1, Rsad2, Isg20). The results suggest that stress may affect brain functions through the stress-induced dysfunction of the vascular system. An important issue raised in our work is also the risk of the contamination of brain tissue samples with choroid plexus. Such contamination would result in a consistent up- or down regulation of genes, such as Ttr, Igf2, Igfbp2, Prlr, Enpp2, Sostdc1, 1500015O10RIK (Ecrg4), Kl, Clic6, Kcne2, F5, Slc4a5, and Aqp1. Our study suggests that some of the previously reported, supposedly specific changes in hippocampal gene expression, may be a result of the inclusion of choroid plexus in the hippocampal samples. PMID- 26556048 TI - Twelve-Year Retention Rate of First-Line Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: Real-Life Data From a Local Registry. AB - OBJECTIVE: To evaluate the 12-year survival of the first tumor necrosis factor inhibitor (TNFi) treatment in a cohort of rheumatoid arthritis (RA) patients, comparing the between-groups discontinuation rates for infliximab, etanercept, and adalimumab. METHODS: RA patients treated with their first TNFi were investigated from a local registry. Before and after adjusting for propensity scores, overall and by individual TNFi 12-year drug retention was evaluated. Drug survival rates were calculated using the Kaplan-Meier method and compared by the Cox extended model. Subanalyses were performed according to concomitant methotrexate (MTX) and discontinuation reasons. RESULTS: Of 583 patients, 222 were treated with infliximab, 179 with etanercept, and 182 with adalimumab; 33.7% and 26% discontinued the first TNFi because of inefficacy or adverse events, respectively. The overall 12-year drug survival rate for the unmatched population was 23.4%. In the propensity score-adjusted population, the hazard ratio (HR) for treatment discontinuation was significantly greater for adalimumab and infliximab versus etanercept (HR 2.89 [95% confidence interval (95% CI) 2.2-3.78] and HR 2.56 [95% CI 1.92-3.4], respectively), and no difference was found between and for adalimumab versus infliximab (HR 1.16 [95% CI 0.91-1.47]). The incidence of withdrawal due to secondary inefficacy was stable from 3 to 12 years for etanercept, but progressively increased for the monoclonal antibodies. Concomitant MTX significantly increased the survival of both adalimumab and etanercept (HR 1.48 [95% CI 1.18-1.86]). CONCLUSION: The overall 12-year drug survival rate was 23.4%, being significantly higher for etanercept than adalimumab and infliximab. Etanercept discontinuations for inefficacy did not increase from 3 to 12 years. Concomitant MTX increased adalimumab and etanercept drug survival. PMID- 26556049 TI - Spatial and temporal analyses of metrics of tuberculosis infection in badgers (Meles meles) from the Republic of Ireland: Trends in apparent prevalence. AB - Badgers are a wildlife host of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and an important contributor to the epidemiology of bTB in cattle in Ireland and Britain. Repeated culling of badgers in high prevalence cattle bTB areas has been used in the Republic of Ireland as one tool to reduce intra- and interspecific transmission of M. bovis. We assessed factors that influenced infection prevalence of culled badgers from 2009 to 2012 (n=4948) where spatial, temporal and intrinsic factor data were available using multivariable modelling. Prevalence appeared higher in western areas than eastern areas of Ireland and badgers were more likely to be test-positive if caught at a sett (burrow system) which was close to other infected setts (spatial clustering of infection). There was a significant positive association between badger test status and cattle prevalence of M. bovis infection at a spatial scale of 1km around setts. Badgers were more likely to be deemed test positive if they were male (OR: 1.9) or a parous female (OR: 1.7), compared to a female who had never conceived. Our results are consistent with different groups within badger populations having differential exposures and therefore infection risk (for example, parous vs. non-parous females). Furthermore, bTB clusters within the badger population, with greater risk to badgers in setts that are closest to other infected setts. The effective scale of the association of bTB risk between badger and cattle populations may be relatively large in Ireland. Our data indicate that the overall trend in prevalence of M. bovis infection in badgers has decreased in Ireland (P<0.001) while controlling for significant confounders over the study period, and follows a longer temporal trend from 2007 to 2013, where unadjusted apparent prevalence declined from 26% to 11% during 2007 to mid 2011, followed by a stable trend between 9 and 11% thereafter (n=10,267). PMID- 26556050 TI - Introduction to the special issue: Diseases, dilemmas, decisions: Epidemiological tools to find answers for difficult disease control problems. SCHWABE 2014 Symposium Honoring the Legacy of Dr Roger Morris. PMID- 26556052 TI - African humid periods triggered the reactivation of a large river system in Western Sahara. AB - The Sahara experienced several humid episodes during the late Quaternary, associated with the development of vast fluvial networks and enhanced freshwater delivery to the surrounding ocean margins. In particular, marine sediment records off Western Sahara indicate deposition of river-borne material at those times, implying sustained fluvial discharges along the West African margin. Today, however, no major river exists in this area; therefore, the origin of these sediments remains unclear. Here, using orbital radar satellite imagery, we present geomorphological data that reveal the existence of a large buried paleodrainage network on the Mauritanian coast. On the basis of evidence from the literature, we propose that reactivation of this major paleoriver during past humid periods contributed to the delivery of sediments to the Tropical Atlantic margin. This finding provides new insights for the interpretation of terrigenous sediment records off Western Africa, with important implications for our understanding of the paleohydrological history of the Sahara. PMID- 26556053 TI - Rational design of a carboxylic esterase RhEst1 based on computational analysis of substrate binding. AB - A new carboxylic esterase RhEst1 which catalyzes the hydrolysis of (S)-(+)-2,2 dimethylcyclopropanecarboxylate (S-DmCpCe), the key chiral building block of cilastatin, was identified and subsequently crystallized in our previous work. Mutant RhEst1A147I/V148F/G254A was found to show a 5-fold increase in the catalytic activity. In this work, molecular dynamic simulations were performed to elucidate the molecular determinant of the enzyme activity. Our simulations show that the substrate binds much more strongly in the A147I/V148F/G254A mutant than in wild type, with more hydrogen bonds formed between the substrate and the catalytic triad and the oxyanion hole. The OH group of the catalytic residue Ser101 in the mutant is better positioned to initiate the nucleophilic attack on S-DmCpCe. Interestingly, the "170-179" loop which is involved in shaping the catalytic sites and facilitating the product release shows remarkable dynamic differences in the two systems. Based on the simulation results, six residues were identified as potential "hot-spots" for further experimental testing. Consequently, the G126S and R133L mutants show higher catalytic efficiency as compared with the wild type. This work provides molecular-level insights into the substrate binding mechanism of carboxylic esterase RhEst1, facilitating future experimental efforts toward developing more efficient RhEst1 variants for industrial applications. PMID- 26556054 TI - Probing the Carbonyl Functionality of a Petroleum Resin and Asphaltene through Oximation and Schiff Base Formation in Conjunction with N-15 NMR. AB - Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, beta-hydroxyketones, beta-diketones, and beta ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected. PMID- 26556051 TI - Effect of Intravascular Ultrasound-Guided vs Angiography-Guided Everolimus Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial. AB - IMPORTANCE: Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE: To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS: The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent >=28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS: Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS: One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, -2.97% [95% CI, -5.14% to -0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion-related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion-related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE: Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308281. PMID- 26556055 TI - High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients' Perceptions on Initiation, Reasons for Use, and Obtainment. AB - BACKGROUND: High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. METHODS: We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group's views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring's qualitative content analysis was used to evaluate our data. RESULTS: In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. CONCLUSIONS: Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients' motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective. PMID- 26556057 TI - Patient Compliance in Home-Based Self-Care Telehealth Projects. AB - This paper presents the findings of a literature review on patient compliance in home-based self-care telehealth monitoring situations, intended to establish a knowledge base for this aspect which is often neglected alongside more conventional clinical, economic and service evaluations. A systematic search strategy led to 72 peer-reviewed published scientific papers being selected as most relevant to the topic, 58 of which appeared in the last 10 years. Patient conditions in which most evidence for compliance was found were blood pressure, heart failure and stroke, diabetes, asthma, chronic obstructive pulmonary disease and other respiratory diseases. In general, good compliance at the start of a study was found to drop off over time, most rapidly in the period immediately after the start. Success factors identified in the study included the extent of patient health education, telehealth system implementation style, user training and competence in system usage, active human support from the healthcare provider and maintaining strong participant motivation. PMID- 26556058 TI - Telemedicine in the acute health setting: A disruptive innovation for specialists (an example from stroke). AB - INTRODUCTION: Telemedicine is a disruptive innovation within health care settings as consultations take place via audio-visual technology rather than traditional face-to-face. Specialist perceptions and experiences of providing audio-visual consultations in emergency situations, however, are not well understood. The aim of this exploratory study was to describe the experience of medical specialists providing acute stroke decision-making support via telemedicine. METHODS: Data from the Victorian Stroke Telemedicine (VST) programme were used. The experiences of specialists providing an acute clinical telemedicine service to rural emergency departments were explored, drawing on disruptive innovation theory. Document analysis of programme consultation records, meeting minutes and in-depth individual interviews with three neurologists were analysed using triangulation. RESULTS: Since February 2014, 269 stroke telemedicine consultations with 12 neurologists have occurred. Retention on the roster has varied between 1 and >4 years. Overall, neurologists reported benefits of participation, as they were addressing health equity gaps for rural patients. Negative effects were the unpredictability of consultations impacting on their personal life, the mixed level of experience of colleagues initiating the consult and not knowing patient outcomes since follow-up communication was not routine. CONCLUSIONS: Insights into workforce experience and satisfaction were identified to inform strategies to support specialists to adapt to the disruptive innovation of telemedicine. PMID- 26556056 TI - Evolution of the EKA family of powdery mildew avirulence-effector genes from the ORF 1 of a LINE retrotransposon. AB - BACKGROUND: The Avrk1 and Avra10 avirulence (AVR) genes encode effectors that increase the pathogenicity of the fungus Blumeria graminis f.sp. hordei (Bgh), the powdery mildew pathogen, in susceptible barley plants. In resistant barley, MLK1 and MLA10 resistance proteins recognize the presence of AVRK1 and AVRA10, eliciting the hypersensitive response typical of gene for gene interactions. Avrk1 and Avra10 have more than 1350 homologues in Bgh genome, forming the EKA (Effectors homologous to Avr k 1 and Avr a 10) gene family. RESULTS: We tested the hypothesis that the EKA family originated from degenerate copies of Class I LINE retrotransposons by analysing the EKA family in the genome of Bgh isolate DH14 with bioinformatic tools specially developed for the analysis of Transposable Elements (TE) in genomes. The Class I LINE retrotransposon copies homologous to Avrk1 and Avra10 represent 6.5 % of the Bgh annotated genome and, among them, we identified 293 AVR/effector candidate genes. We also experimentally identified peptides that indicated the translation of several predicted proteins from EKA family members, which had higher relative abundance in haustoria than in hyphae. CONCLUSIONS: Our analyses indicate that Avrk1 and Avra10 have evolved from part of the ORF1 gene of Class I LINE retrotransposons. The co-option of Avra10 and Avrk1 as effectors from truncated copies of retrotransposons explains the huge number of homologues in Bgh genome that could act as dynamic reservoirs from which new effector genes may evolve. These data provide further evidence for recruitment of retrotransposons in the evolution of new biological functions. PMID- 26556059 TI - A telegeriatric service in a small rural hospital: A case study and cost analysis. AB - INTRODUCTION: Small hospitals in rural areas usually have an insufficient caseload of frail old people to justify the regular presence of a geriatrician. This study examined the costs of providing a telegeriatric service by videoconference in a rural hospital, compared to the costs of a visiting geriatrician that travels to undertake in-person consultations. METHODS: A cost analysis was undertaken to compare the costs of the telegeriatric service model with the costs of a visiting geriatrician service model. A recently established telegeriatric service at Warwick Hospital was used as a case study. RESULTS: In the base case model (assuming four patients per round and a round-trip travel distance of 312 kilometres), an estimated AUD$131 per patient consultation can be saved in favour of the telegeriatric service model. Key drivers of costs are the number of patients per round and the travel distance and time in the visiting geriatrician model. At a workload of four patients per round, it is less expensive to conduct a telegeriatric service than a visiting geriatrician service when the round-trip travel time exceeds 76 minutes. DISCUSSION: Even under quite conservative assumptions, a telegeriatric service offers an economically feasible approach to the delivery of specialist geriatric assessment in rural and remote settings. PMID- 26556060 TI - Effectiveness of a teleaudiology approach to hearing aid fitting. AB - This research was conducted to evaluate the efficacy of an online speech perception test (SPT) for the measurement of hearing and hearing aid fitting in comparison with conventional methods. Phase 1 was performed with 88 people to evaluate the SPT for the detection of significant hearing loss. The SPT had high sensitivity (94%) and high selectivity (98%). In Phase 2, phonetic stimulus response matrices derived from the SPT results for 408 people were used to calculate "InfogramsTM." At every frequency, there was a highly significant correlation (p < 0.001) between hearing thresholds derived from the Infogram and conventional audiograms. In Phase 3, initial hearing aid fittings were derived from conventional audiograms and Infograms for two groups of hearing impaired people. Unaided and aided SPTs were used to measure the perceptual benefit of the aids for the two groups. The mean increases between unaided and aided SPT scores were 19.6%, and 22.2% (n = 517, 484; t = 2.2; p < 0.05) for hearing aids fitted using conventional audiograms and Infograms respectively. The research provided evidence that the SPT is a highly effective tool for the detection and measurement of hearing loss and hearing aid fitting. Use of the SPT reduces the costs and increases the effectiveness of hearing aid fitting, thereby enabling a sustainable teleaudiology business model. PMID- 26556061 TI - Identifying perceived barriers to videoconferencing by rehabilitation medicine providers. AB - The aim of this study was to identify barriers to the utilisation of videoconferencing within a multidisciplinary rehabilitation medicine healthcare team, as the first step towards creating a telerehabilitation service. A survey was developed on videoconference use and barriers to use, and distributed to healthcare providers including rehabilitation medicine societies and allied health societies through an anonymous link to SurveyMonkey((r)). There were 254 respondents, practicing primarily in Australia (n = 245), in various healthcare roles. One-hundred and fifty-nine (66%) of respondents used videoconferencing regularly, primarily for their own education. Respondents not currently utilising videoconferencing (n = 82, 34%) ranked the reasons for this and provided free text responses to explain why this modality was not being utilised in practice. Respondents were reluctant to use videoconferencing because of perceived increase in time needed for video consultations compared to face-to-face consultations, concerns with lack of privacy and confidentiality, and a lack of clinical practice guidelines for video consultation. We believe many barriers to videoconferencing by healthcare providers can be managed with appropriate education and targeted training. Future research studies, which focus on standards and clinical practice guidelines for videoconferencing by healthcare providers, may result in increased utilisation of this modality for healthcare delivery in rehabilitation medicine. PMID- 26556062 TI - An evaluation of the benefits and challenges of video consulting between general practitioners and residential aged care facilities. AB - This research evaluated a project that provided video consultations between general practitioners (GPs) and residential aged care facilities (RACFs), with the aim of enabling faster access to medical care and avoidance of unnecessary hospital transfers. GPs were paid for video consultations at a rate equivalent to existing insurance reimbursement for supporting telehealth services. Evaluation data were gathered by direct observation at the project sites, semi-structured interviews and video call data from the technical network. Three pairs of general practices and RACFs were recruited to the project. 40 video consultations eligible for payment occurred over a 6 month period, three of which were judged to have avoided hospital attendance. The process development and change management aspects of the project required substantially more effort than was anticipated. This was due to problems with RACF technical infrastructure, the need for repeated training and awareness raising in RACFs, the challenge of establishing new clinical procedures, the short length of the project and broader difficulties in the relationships between GPs and RACFs. Video consulting between GPs and RACFs was clinically useful and avoided hospital attendance on a small scale, but further focus on process development is needed to embed this as a routine method of service delivery. PMID- 26556063 TI - miRNAs are required for the terminal differentiation of white matter astrocytes in the developing CNS. AB - While the regulation of the neurogenesis and oligodendrogenesis by microRNAs has been intensively studied, little is known about the role of microRNAs (miRNAs) in the development of astrocytes. Here, we report that microRNAs play an essential role in the differentiation and maturation of white matter astrocytes in mouse spinal cord tissues. In glial fibrillary acidic protein (GFAP)/Dicer conditional mutants, the initial generation of astrocyte progenitor cells was normal in the spinal cord. However, there was a much reduced number of GFAP+ astrocytes with shorter processes in the white matter of mutant tissues. In contrast, the expression of gray matter protoplasmic astrocyte marker was not affected. Together, our studies indicated that miRNAs are required for the differentiation and morphological maturation of white matter fibrous astrocytes in the developing spinal cord. PMID- 26556064 TI - Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats. AB - High levels of chronic stress or stress hormones are associated with depressive like behavior in animal models. However, slight elevations in corticosterone (CORT) - the major stress hormone in rodents - have also been associated with improved performances, albeit in a sex-dependent manner. Some of the discrepancies in the literature regarding the effects of high CORT levels may be due to different administrations methods. The current study aims to compare the effects of ~40mg/kg given either via subcutaneous injection, through an implanted pellet, or in the drinking water, for ~21days on CORT serum levels, depressive like behavior in the forced swim test (FST), and neurogenesis levels in the dentate gyrus (DG) in adult female rats. We found that animals exposed to the daily injections showed elevated CORT levels throughout the administration period, while the pellet animals showed only a transient increase, and drinking water animals revealed no elevation in CORT in serum. In addition, only the injection group exhibited higher levels of immobility in the FST. Interestingly, animals receiving CORT via injection or drinking water had lower numbers of doublecortin-positive cells in the ventral DG one week after the last CORT administration compared to animals implanted with a CORT pellet. These results will contribute to the growing literature on the effects of chronic CORT exposure and may help to clarify some of the discrepancies among previous studies, particularly in females. PMID- 26556065 TI - Phantom hand and wrist movements in upper limb amputees are slow but naturally controlled movements. AB - After limb amputation, patients often wake up with a vivid perception of the presence of the missing limb, called "phantom limb". Phantom limbs have mostly been studied with respect to pain sensation. But patients can experience many other phantom sensations, including voluntary movements. The goal of the present study was to quantify phantom movement kinematics and relate these to intact limb kinematics and to the time elapsed since amputation. Six upper arm and two forearm amputees with various delays since amputation (6months to 32years) performed phantom finger, hand and wrist movements at self-chosen comfortable velocities. The kinematics of the phantom movements was indirectly obtained via the intact limb that synchronously mimicked the phantom limb movements, using a Cyberglove(r) for measuring finger movements and an inertial measurement unit for wrist movements. Results show that the execution of phantom movements is perceived as "natural" but effortful. The types of phantom movements that can be performed are variable between the patients but they could all perform thumb flexion/extension and global hand opening/closure. Finger extension movements appeared to be 24% faster than finger flexion movements. Neither the number of types of phantom movements that can be executed nor the kinematic characteristics were related to the elapsed time since amputation, highlighting the persistence of post-amputation neural adaptation. We hypothesize that the perceived slowness of phantom movements is related to altered proprioceptive feedback that cannot be recalibrated by lack of visual feedback during phantom movement execution. PMID- 26556066 TI - Harmaline-induced amnesia: Possible role of the amygdala dopaminergic system. AB - In this study, we examined the effect of bilateral intra-basolateral amygdala (intra-BLA) microinjections of dopamine receptor agents on amnesia induced by a beta-carboline alkaloid, harmaline in mice. We used a step-down method to assess memory and then, hole-board method to assess exploratory behaviors. The results showed that pre-training intra-BLA injections of dopamine D1 receptor antagonist and agonist (SCH23390 (0.5MUg/mouse) and SKF38393 (0.5MUg/mouse), respectively) impaired memory acquisition. In contrast, pre-training intra-BLA injections of dopamine D2 receptor antagonist and agonist (sulpiride and quinpirole, respectively) have no significant effect on memory acquisition. Pre-training intra-peritoneal (i.p.) injection of harmaline (1mg/kg) decreased memory acquisition. However, co-administration of SCH 23390 (0.01MUg/mouse) with different doses of harmaline did not alter amnesia. Conversely, pre-training intra-BLA injection of SKF38393 (0.1MUg/mouse), sulpiride (0.25MUg/mouse) or quinpirole (0.1MUg/mouse) reversed harmaline (1mg/kg, i.p.)-induced amnesia. Furthermore, all above doses of drugs had no effect on locomotor activity. In conclusion, the dopamine D1 and D2 receptors of the BLA may be involved in the impairment of memory acquisition induced by harmaline. PMID- 26556067 TI - Optimization of Manganese Reduction in Biotreated POME onto 3A Molecular Sieve and Clinoptilolite Zeolites. AB - Availability of quality-certified water is pertinent to the production of food and pharmaceutical products. Adverse effects of manganese content of water on the corrosion of vessels and reactors necessitate that process water is scrutinized for allowable concentration levels before being applied in the production processes. In this research, optimization of the adsorption process conditions germane to the removal of manganese from biotreated palm oil mill effluent (BPOME) using zeolite 3A subsequent to a comparative adsorption with clinoptilolite was studied. A face-centered central composite design (FCCCD) of the response surface methodology (RSM) was adopted for the study. Analysis of variance (ANOVA) for response surface quadratic model revealed that the model was significant with dosage and agitation speed connoting the main significant process factors for the optimization. R(2) of 0.9478 yielded by the model was in agreement with predicted R(2). Langmuir and pseudo-second-order suggest the adsorption mechanism involved monolayer adsorption and cation exchanging. PMID- 26556068 TI - Activity-Dependent Neurorehabilitation Beyond Physical Trainings: "Mental Exercise" Through Mirror Neuron Activation. AB - The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot make such efforts. Here the authors proposed the employment of mirror neurons system in promoting brain rehabilitation by "observation based stimulation". Mirror neuron system has been considered as an important basis for action understanding and learning by mimicking others. During the action observation, mirror neuron system mediated the direct activation of the same group of motor neurons that are responsible for the observed action. The effect is clear, direct, specific and evolutionarily conserved. Moreover, recent evidences hinted for the beneficial effects on stroke patients after mirror neuron system activation therapy. Finally some music-relevant therapies were proposed to be related with mirror neuron system. PMID- 26556069 TI - Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence. AB - Exercise promotes several health benefits, such as cardiovascular, musculoskeletal and cardiorespiratory improvements. It is believed that the practice of exercise in individuals with psychiatric disorders, e.g. schizophrenia, can cause significant changes. Schizophrenic patients have problematic lifestyle habits compared with general population; this may cause a high mortality rate, mainly caused by cardiovascular and metabolic diseases. Thus, the aim of this study is to investigate changes in physical and mental health, cognitive and brain functioning due to the practice of exercise in patients with schizophrenia. Although still little is known about the benefits of exercise on mental health, cognitive and brain functioning of schizophrenic patients, exercise training has been shown to be a beneficial intervention in the control and reduction of disease severity. Type of training, form of execution, duration and intensity need to be better studied as the effects on physical and mental health, cognition and brain activity depend exclusively of interconnected factors, such as the combination of exercise and medication. However, one should understand that exercise is not only an effective nondrug alternative, but also acts as a supporting linking up interventions to promote improvements in process performance optimization. In general, the positive effects on mental health, cognition and brain activity as a result of an exercise program are quite evident. Few studies have been published correlating effects of exercise in patients with schizophrenia, but there is increasing evidence that positive and negative symptoms can be improved. Therefore, it is important that further studies be undertaken to expand the knowledge of physical exercise on mental health in people with schizophrenia, as well as its dose-response and the most effective type of exercise. PMID- 26556070 TI - Effects of Different Types of Physical Exercise on the Perceived Quality of Life in Active Elderly. AB - There is a lack of knowledge about the influence of individual physical activities on the quality of life (QoL) of older adults, especially in strength training and swimming, two popular activities. OBJECTIVES: To assess and compare the perceived QoL levels among sedentary, swimming and strength training groups in elderly individuals. METHODS: Twenty one subjects were evaluated: 9 sedentary, 10 swimming and 12 strength training. Physical activity levels were assessed by the International Physical Activity Questionnaire short version, and the physical, psychological, social and environmental domains, as well the general QoL of each group, were assessed through the World Health Organization questionnaire short version. In addition, the contribution of each domain in general QoL was also verified. RESULTS: The sedentary group presented a statistically lower score in each variable examined (p<0.05). The physical domain was higher only in the strength training group and the psychological and social domains were higher only in the swimming group. In relation to the influence on general QoL, the physical domain (i.e., sedentary); the physical and psychological domains (i.e., swimming) and the social and environmental domains (i.e., strength training) were statistically significant. CONCLUSION: The results suggest that the QoL levels were always lower in the sedentary group. However, the determination of the domain depended on the physical activity level of each subject. Further, the domains with better scores were not necessarily the ones that showed a higher association with the general QoL in each group. PMID- 26556071 TI - From Mind to Body: Is Mental Practice Effective on Strength Gains? A Meta Analysis. AB - Mental practice is an internal reproduction of a motor act (whose intention is to promote learning and improving motor skills). Some studies have shown that other cognitive strategies also increase the strength and muscular resistance in healthy people by the enhancement of the performance during dynamic tasks. Mental training sessions may be primordial to improving muscle strength in different subjects. The aim of this study was to systematically review and meta-analiyze studies that assessed whether mental practice is effective in improving muscular strength. We conducted an electronic-computed search in Pub-Med/Medline and ISI Web of Knowledge, Scielo and manual searchs, searching papers written in English between 1991 and 2014. There were 44 studies in Pub-Med/Medline, 631 in ISI Web of Knowledge, 11 in Scielo and 3 in manual searchs databases. After exclusion of studies for duplicate, unrelated to the topic by title and summary, different samples and methodologies, a meta-analysis of 4 studies was carried out to identify the dose-response relationship. We did not find evidence that mental practice is effective in increasing strength in healthy individuals. There is no evidence that mental practice alone can be effective to induce strength gains or to optimize the training effects. PMID- 26556072 TI - Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise? AB - Physical exercise has long been recognized to benefit locomotor and cardiovascular systems. Although an increasing body of evidence also suggests it to be an effective non-medicinal remedy for mental disorders such as depression, the underlying mechanisms remain elusive. A recent study has demonstrated that increases of the adipocyte-secreted hormone adiponectin in the central nervous system following exercise may be responsible for these neuropsychological changes, including enhanced generation of neurons in the adult hippocampus, as well as mitigation of depressive severity. The present review introduces the previously-reported functions of adult hippocampal neurogenesis and adiponectin, and discusses the potential relevance of adiponectin signaling in exercise induced neural changes. Revealing these novel biological effects of adiponectin in the brain may help hunt reliable biomarkers to better guide the anti depressive therapy with exercise intervention; meanwhile, pharmaceutical agents that raise endogenous levels of adiponectin or mimic its biological effects might serve as a replacement for physical exercise. PMID- 26556073 TI - Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients. AB - The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brain-derived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions. PMID- 26556074 TI - Whole Body Vibration Training Improves Walking Performance of Stroke Patients with Knee Hyperextension: A Randomized Controlled Pilot Study. AB - OBJECTIVE: To investigate the effect of 8-week whole body vibration training on gait performance and lower extremity function in stroke patients with knee hyperextension. METHODS: Total 30 subjects with stroke were randomized into the control group (n=15) or the intervention group (n=15). The patients of intervention group were treated with whole body vibration while the control group was treated with placebo. The walking function, lower limb function and knee hyperextension times were assessed in this study. Gait performances were evaluated by 10-meter walk test. The knee hyperextension times was visually observed and counted. The lower limb function was evaluated by Fugl-Meyer motor assessment. RESULTS: The times of the knee hyperextension of the intervention group was significantly decreased compared with control groups (P=0.000, d=1.749, 95%CI[2.915,7.285]). The walking function assessed by 10-meter test of intervention group was significantly improved compared with control group (P=0.001, d=1.345, 95%CI[1.896,6.704]). The performances of all the three tests were improved after training in both groups (P=0.000/P=0.000, d=1.500/d=1.952, 95%CI[3.309,9.891]/ 95%CI[5.549,12.45]; P=0.000/P=0.000, d=2.015/d=2.952, 95%CI[5.214,11.39]/95%CI[9.423, 15.98]; P=0.000/P=0.000, d=3.537/d=5.108, 95%CI[19.05,12.35]/95%CI[16.52,22.28]). CONCLUSION: The results suggest that 8 weeks whole body vibration training can reduce knee hyperextension and increase ambulatory speed in stroke patients. PMID- 26556075 TI - Neural Mechanisms of Exercise: Effects on Gut Miccrobiota and Depression. AB - Microbiota is a set of microorganisms resident in gut ecosystem that reacts to psychological stressful stimuli, and is involved in depressed or anxious status in both animals and human being. Interestingly, a series of studies have shown the effects of physical exercise on gut microbiota dynamics, suggesting that gut microbiota regulation might act as one mediator for the effects of exercise on the brain. Recent studies found that gut microbiota dynamics are also regulated by metabolism changes, such as through physical exercise or diet change. Interestingly, physical exercise modulates different population of gut bacteria in compared to food restriction or rich diet, and alleviates gut syndromes to toxin intake. Gut microbiota could as well contribute to the beneficial effects of exercise on cognition and emotion, either directly through serotonin signaling or indirectly by modulating metabolism and exercise performance. PMID- 26556076 TI - Neural Mechanism of Exercise: Neurovascular Responses to Exercise. AB - Physical exercise is responsible for different metabolic and hemodynamic changes, including increased cerebral blood flow and perfusion. It is known that running increases vascular endothelial growth factor expression in the brain, which is critical for the anti-depressive effects of adult neurogenesis induced by physical exercise. Both animal and human studies revealed that neurovascular responses to physical exercise are well correlated to adult hippocampal neurogenesis and cognition improvement. Yet it is unknown if the increased blood perfusion to hippocampus is affecting the adult neurogenesis. Manipulating systemic blood pressure, or stimulating the cerebral blood flow with alternative measures, might provide useful tools to understand how much neurovascular plasticity contributes to the brain cognition enhancement by physical exercise. In addition, it will be interesting to examine the responses of brain cells (including neuron, glia and endothelia cells) to increased shear stress and oxygen load, to investigate the underlying molecular mechanisms. PMID- 26556077 TI - Neural Mechanisms of Exercise: Anti-Depression, Neurogenesis, and Serotonin Signaling. AB - Depression is associated with decreased serotonin metabolism and functioning in the central nervous system, evidenced by both animal models of depression and clinical patient studies. Depression is also accompanied by decreased hippocampal neurogenesis in diverse animal models. Neurogenesis is mainly defined in dentate gyrus of hippocampus as well as subventricular zone. Moreover, hypothalamus, amygdala, olfactory tubercle, and piriform cortex are reported with evidences of adult neurogenesis. Physical exercise is found to modulate adult neurogenesis significantly, and results in mood improvement. The cellular mechanism such as adult neurogenesis upregulation was considered as one major mood regulator following exercise. The recent advances in molecular mechanisms underlying exercise-regulated neurogenesis have widen our understanding in brain plasticity in physiological and pathological conditions, and therefore better management of different psychiatric disorders. PMID- 26556078 TI - 5 Hz Repetitive Transcranial Magnetic Stimulation with Maximum Voluntary Muscle Contraction Facilitates Cerebral Cortex Excitability of Normal Subjects. AB - BACKGROUND: Recently, high-frequency repetitive transcranial magnetic stimulation (rTMS) is reported to evaluating the corticospinal pathway and improving both cortical excitability and motor function significantly in subjects. According to some previous reports, the maximum voluntary muscle contraction (MVC) of target muscle can reinforce the influence by rTMS. The aim of this study was to confirm 5 Hz rTMS with MVC in healthy individuals is an effective method to facilitate motor neuron excitability and the efficiency can last at least 30 min post stimulation. OBJECTIVE: To compare the motor evoked potentials (MEPs) elicited by 5Hz rTMS and 5Hz rTMS combined with MVC. METHODS: In this randomized, controlled, assessor-blinded, crossover trial, 40 healthy right-handed subjects were divided into group A (n=20) and group B (n=20). All subjects received rTMS over the primary motor cortex area (M1) in the left hemisphere. The parameters of rTMS were 5 Hz, 90.of the resting motor threshold (RMT), for a total of 500 pulses in 100 trains (1-sec inter-stimulus and 8- sec inter-interval). Method 1: All subjects received rTMS over the hand area of left M1. Method 2: All subjects received rTMS at the same stimulated point, combined with maximum voluntary hand griping in each 10 trains. Test 1: group A underwent method 1, while group B underwent method 2. Test 2: A week later, group B underwent method 1, while group A underwent method 2. In each test, the MEP amplitude and latency was measured before (P-rTMS), 5 min after (Post 1) and 30 min after (Post 2) the rTMS intervention. RESULTS: MEP amplitude increased significantly from baseline at 5 minutes post intervention under both treatment regimes. However for both sequences, it decreased towards baseline under the rTMS intervention at 30 minutes post intervention but remained relatively high when rTMS was combined with MVC. MEP latency decreased significantly from baseline at 5 minutes post intervention under both treatment regimes. For both sequences, it then increased again towards baseline under both treatment regimes at 30 minutes post intervention. Although there was a trend for a less pronounced increase under the combined treatment, this effect was not significant. CONCLUSION: Both 5 Hz rTMS and 5 Hz rTMS combined with MVC facilitate motor cortical excitability, but the enhancement in rTMS with MVC is more pronounced and maintained longer than simple rTMS. PMID- 26556079 TI - Comparing the Effects of Drug Therapy, Perceptual Motor Training, and Both Combined on the Motor Skills of School-Aged Attention Deficit Hyperactivity Disorder Children. AB - The purpose of this research was to compare the effects of drug therapy, perceptual motor training and a combination of drug therapy and perceptual motor training on gross and fine motor skills of 6 to 12 year-old Iranian attention deficit hyperactivity disorder children. Thirty-six attention deficit hyperactivity disorder children currently under treatment in three Iranian psychological-neurological clinics participated in this research study. Participants were sampled from the accessible population and randomly assigned to three experimental groups (n = 12 each). The Conners Parent Rating Scale was used to classify the children and the Bruininks-Oseretsky Test of Motor Proficiency was administered before and after a three month treatment/ training session. Participants in the first experimental group received drug therapy (including methylphenidate). In the second group participants took part in 18 sessions of perceptual-motor skill training for six consecutive weeks, and in the third group children received both interventions. The results indicated that interventions using perceptual-motor training alone or in combination with a drug therapy significantly improved both gross and fine motor skills over a period of six weeks. Participants in the drug-only group showed no improvement in motor performance. PMID- 26556080 TI - The Effects of Aerobic Exercise on Cognitive Function of Alzheimer's Disease Patients. AB - To evaluate the effect of moderate intensity of aerobic exercise on elderly people with mild Alzheimer's disease, we recruited fifty volunteers aged 50 years to 80 years with cognitive impairment. They were randomized into two groups: aerobic group (n=25) or control group (n=25). The aerobic group was treated with cycling training at 70% of maximal intensity for 40 min/d, 3 d/wk for 3 months. The control group was only treated with heath education. Both groups were received cognitive evaluation, laboratory examination before and after 3 months. The results showed that the Minimum Mental State Examination score, Quality of Life Alzheimer's Disease score and the plasma Apo-a1 level was significantly increased (P<0.05), the Alzheimer's Disease Assessment Scale-cognition score, Neuropsychiatric Inventory Questionnaire score was significantly decreased.(P<0.05) in aerobic group before and after 3 months in aerobic group. For the control group, there was no significant difference in scores of Alzheimer's Disease Assessment Scale-cognition, Neuropsychiatric Inventory Questionnaire, Quality of Life Alzheimer's Disease, Apo-a1 (P>0.05), while Minimum Mental State Examination scores decreased significantly after 3 months (P<0.05). In conclusion, moderate intensity of aerobic exercise can improve cognitive function in patients with mild Alzheimer's disease. PMID- 26556081 TI - The implicit Power Motive and Adolescents' Salivary Cortisol Responses to Acute Psychosocial Stress and Exercise in School. AB - In the present study we examined the moderating effect of the power motive on salivary cortisol responses to acute psychosocial stress and exercise in adolescents. Fifty-seven high school students aged M = 14.8 years participated in the study. The Operant Motive Test was applied to measure the implicit power motive and the Personality Research Form was used to measure the explicit power motive. Salivary cortisol levels were assessed before and after the stress stimuli. Participants were randomly assigned to three experimental groups. An exercise group ran 15 minutes at a defined heart rate of 65-75% HRmax. A psychosocial stress group worked on a standard intelligence test for the same amount of time under the assumption, that their test scores will be made public in class after the test. The control group participated in a regular class session. The implicit power motive was significantly associated with increased cortisol levels in the psychosocial stress group. The explicit power motive was not associated with cortisol responses. Findings suggest that the implicit power motive moderates the cortisol responses to acute stress in an adolescent age group with higher responses to psychosocial stress in comparison to exercise or control conditions. PMID- 26556082 TI - Visual Spatial Attention Training Improve Spatial Attention and Motor Control for Unilateral Neglect Patients. AB - OBJECTIVE: To compare the effect of visual spatial training on the spatial attention to that on motor control and to correlate the improvement of spatial attention to motor control progress after visual spatial training in subjects with unilateral spatial neglect (USN). METHOD: 9 cases with USN after right cerebral stroke were randomly divided into Conventional treatment group + visual spatial attention and Conventional treatment group. The Conventional treatment group + visual spatial attention received conventional rehabilitation therapy (physical and occupational therapy) and visual spatial attention training (optokinetic stimulation and right half-field eye patching). The Conventional treatment group was only treated with conventional rehabilitation training (physical and occupational therapy). All patients were assessed by behavioral inattention test (BIT), Fugl-Meyer Assessment of motor function (FMA), equilibrium coordination test (ECT) and non-equilibrium coordination test (NCT) before and after 4 weeks treatment. RESULT: Total scores in both groups (without visual spatial attention/with visual spatial attention) improved significantly (BIT: P=0.021/P=0.000, d=1.667/d=2.116, power=0.69/power=0.98, 95%CI[ 0.8839,45.88]/95%CI=[16.96,92.64]; FMA: P=0.002/P=0.000, d=2.521/d=2.700, power=0.93/power=0.98, 95%CI[5.707,30.79]/95%CI=[16.06,53.94]; ECT: P=0.002/ P=0.000, d=2.031/d=1.354, power=0.90/power=0.17, 95%CI[3.380,42.61]/95%CI=[ 1.478,39.08]; NCT: P=0.013/P=0.000, d=1.124/d=1.822, power=0.41/power=0.56, 95%CI[-7.980,37.48]/95%CI=[4.798,43.60],) after treatment. Among the 2 groups, the group with visual spatial attention significantly improved in BIT (P=0.003, d=3.103, power=1, 95%CI[15.68,48.92]), FMA of upper extremity (P=0.006, d=2.771, power=1, 95%CI[5.061,20.14]) and NCT (P=0.010, d=2.214, power=0.81-0.90, 95%CI[3.018,15.88]). Correlative analysis shows that the change of BIT scores is positively correlated to the change of FMA total score (r=0.77, P<;0.01), FMA of upper extremity (r=0.81, P<0.01), NCT (r=0.78, P<0.01). CONCLUSION: Four weeks visual spatial training could improve spatial attention as well as motor control functions in hemineglect patients. The improvement of motor function is positively correlated to the progresses of visual spatial functions after visual spatial attention training. PMID- 26556083 TI - What Do Athletes Know on the Effect of Steroids? An Exploratory Study in Italy. AB - Despite the evidence of risks related to the use of anabolic steroids for the improvement of athletic performances, the diffusion of such drugs appears to be increasing. An exploratory study was conducted in Cagliari, Italy, to assess the level of information on this issue, to esteem the use of steroids among athletes, to measure the wellbeing of athletes and the risks related to steroid use. A sample of 192 athletes, including 142 non-agonists and 50 agonists (age range: 18 to 36) was invited to fill in a booklet including several self-report questionnaires. The questionnaire for the assessment of the beliefs regarding the effects of anabolic steroids was developed and validated for the study, while the Self Reporting Questionnaire was used for the assessment of the mental health aspects. A general lack of information on the specific effects of steroid use on general and psychic health, as well as on sportive performances was found. Athletes were also quite unaware of the diffusion of steroids among them. Since the sportive environment seems to be the main source of information, this channel should be targeted to address the prevention and information campaigns. The use of more specific tools and the investigation of the perception of reliability of the information sources as well as the social desirability issues should be explored in future studies. PMID- 26556084 TI - Comparison of the Effects of Contralaterally Controlled Functional Electrical Stimulation and Neuromuscular Electrical Stimulation on Upper Extremity Functions in Patients with Stroke. AB - BACKGROUND: Contralaterally controlled functional electrical stimulation (CCFES) is an innovative method to improve upper extremity functions after stroke. OBJECTIVE: To compare the effects of CCFES versus neuromuscular electrical stimulation (NMES) on the upper extremity functions in patients with stroke. METHODS: Sixty patients with stroke were randomly assigned into CCFES group (n=30) or NMES group (n=30). All patients were also treated with conventional medical treatment and rehabilitation training. Patients in CCFES group received CCFES to the affected wrist extensors while the NMES group received NMES. The stimulus current was biphasic wave with a pulse duration of 200 MUs and a frequency of 60 Hz. The electrical stimulation lasted for 20 min per session, 5 sessions per week for 3 weeks. The intensity of the CCFES was based on the electromyography (EMG) value of the unaffected side while the subjects voluntarily extended their unaffected wrist slightly (<10% range of motion, ROM), moderately (about 50% ROM) and completely (100% ROM). Fugl-Meyer assessment (FMA), motricity index (MI), the Hong Kong version of functional test for the hemiplegic upper extremity (FTHUE-HK) and active range of motion (AROM) of wrist extension were measured before and after 3 weeks of treatment. RESULTS: Compared with the baseline values, both groups showed significant improvements in all the measurements after treatment (p<0.05). Patients in CCFES group showed significantly higher upper extremity FMA, FTHUE-HK scores and AROM of wrist extension than those in NMES group (p<0.05). CONCLUSION: Compared with the conventional NMES, CCFES provides better recovery of upper extremity function in patients with stroke. PMID- 26556085 TI - Potential Therapeutic Effects of Physical Exercise for Bipolar Disorder. AB - Cognitive deficits are observed in a variety of domains in patients with bipolar disorder (BD). These deficits are attributed to neurobiological, functional and structural brain factors, particularly in prefrontal cortex. Furthermore, cortical alterations in each phase (mania/hypomania, euthymia and depression) are also present. A growing basis of evidence supports aerobic exercise as an alternative treatment method for BD symptoms. Its benefits for physical health in healthy subjects and some psychiatric disorders are fairly established; however evidence directly addressed to BD is scant. Lack of methodological consistency, mainly related to exercise, makes it difficult accuracy and extrapolation of the results. Nevertheless, mechanisms related to BD physiopathology, such as hormonal and neurotransmitters alterations and mainly related to brain-derived neurotrophic factors (BDNF) can be explored. BDNF, specially, have a large influence on brain ability and its gene expression is highly responsive to aerobic exercise. Moreover, aerobic exercise trough BDNF may induce chronic stress suppression, commonly observed in patients with BD, and reduce deleterious effects caused by allostatic loads. Therefore, it is prudent to propose that aerobic exercise plays an important role in BD physiopathological mechanisms and it is a new way for the treatment for this and others psychiatric disorders. PMID- 26556086 TI - Prediction of Affective Responses in Aerobic Exercise Sessions. AB - The objective of the present study was to verify which physiological (percentage of maximum oxygen consumption--%VO2 or percentage of maximum heart rate--%HR) or psychological (ratings of perceived exertion--RPE) variable is the best predictor of affective responses during continuous (CT) and interval (HIT) exercise sessions. Fourteen men underwent 3 exercise sessions on the treadmill. In the first session, a graded exercise test was performed to determine the maximum HR, peak VO2, and the respiratory compensation point (RCP). Then, participants performed the CT and HIT exercise in a counterbalanced order. The HIT session consisted of 2 min stimuli with an intensity of 100% of peak VO2 interspersed with periods of passive recovery. The average intensities of both exercise sessions were equalized at 85% of RCP. Linear regression analyses of both exercise sessions showed higher prediction values of RPE (CT--R2=.54, p <.01; HIT -R2=.68, p<.01) compared to %VO2 (CT--R2=.04, p=.08; HIT--R2=0.3, p=.12) and %HR (CT--R2=.07, p=.02; HIT--R2=.05, p=.05). Additionally, the results of the linear regression analysis between the Feeling Scale and physiological variables were not significant, indicating that the slope of the regression analysis was not different from zero. These results may be explained by the conscious mental processing required for the manifestation of both the RPE and the affective responses. In conclusion, the affective responses seem to be modulated not only by the intensity of exercise but also mostly by how the individual perceives this intensity. PMID- 26556087 TI - Aging process, cognitive decline and Alzheimer's disease: can strength training modulate these responses? AB - Some evidence shows that aerobic training can attenuate the aging effects on the brain structures and functions. However, the strength exercise effects are poorly discussed. Thus, in the present study, the effects of strength training on the brain in elderly people and Alzheimer's disease (AD) patients were revised. Furthermore, it a biological explanation relating to strength training effects on the brain is proposed. Brain atrophy can be related to neurotransmission dysfunction, like oxidative stress, that generates mitochondrial damage and reduced brain metabolism. Another mechanism is related to amyloid deposition and amyloid tangles, that can be related to reductions on insulin-like growth factor I concentrations. The brain-derived neurotrophic factor also presents reduction during aging process and AD. These neuronal dysfunctions are also related to cerebral blood flow decline that influence brain metabolism. All of these alterations contribute to cognitive impairment and AD. After a long period of strength training, the oxidative stress can be reduced, the brain-derived neurotrophic factor and insulin-like growth factor I serum concentrations enhance, and the cognitive performance improves. Considering these results, we can infer that strength training can be related to increased neurogenesis, neuroplasticity and, consequently, counteracts aging effects on the brain. The effect of strength training as an additional treatment of AD needs further investigation. PMID- 26556088 TI - Effects of School-Based Physical Activity Interventions on Cognition and Academic Achievement: A Systematic Review. AB - Schools are an ideal setting to implement physical activity programs targeted at youths' learning and intellectual abilities, as exercise has been associated with improvement in cognitive skills and academic proficiency. A systematic review of the literature was performed to examine the effects of school-based physical activity interventions on academic achievement and cognitive outcomes. A search for relevant papers was carried out on PubMed/Medline, Scopus and Google Scholar. Only quasi-experimental and experimental studies were included, if focused on school-based physical activity interventions targeting 3 to 18 year-old healthy pupils, and designed to establish a relationship between exercise performed in a school setting and cognitive/academic performance. Thirty-one papers were retrieved by the search, reporting the findings of twenty-eight school-based physical activity interventions. Most of the included studies were published in the past five years. A large majority of the studies showed positive results in terms of academic achievement and, above all, cognitive skills. In the recent years, the number of studies on school-based physical interventions aimed to establish a relationship between physical activity performed in school setting and cognitive/academic outcomes significantly increased, as well as high quality assessments and designs. This review highlights the effectiveness of school-based physical activity interventions on academic achievement and, above all, on youths' cognitive performance. Some interesting findings come from studies assessing brain functional changes, from interventions targeting culturally diverse or low-income samples, and from interventions where physical activity is in the form of active videogames. PMID- 26556089 TI - Effects of Aerobic Exercise on Anxiety Disorders: A Systematic Review. AB - Anxiety disorders are the most common psychiatric disorders observed currently. It is a normal adaptive response to stress that allows coping with adverse situations. Nevertheless, when anxiety becomes excessive or disproportional in relation to the situation that evokes it or when there is not any special object directed at it, such as an irrational dread of routine stimuli, it becomes a disabling disorder and is considered to be pathological. The traditional treatment used is medication and cognitive behavioral psychotherapy, however, last years the practice of physical exercise, specifically aerobic exercise, has been investigated as a new non-pharmacological therapy for anxiety disorders. Thus, the aim of this article was to provide information on research results and key chains related to the therapeutic effects of aerobic exercise compared with other types of interventions to treat anxiety, which may become a useful clinical application in a near future. Researches have shown the effectiveness of alternative treatments, such as physical exercise, minimizing high financial costs and minimizing side effects. The sample analyzed, 66.8% was composed of women and 80% with severity of symptoms anxiety as moderate to severe. The data analyzed in this review allows us to claim that alternative therapies like exercise are effective in controlling and reducing symptoms, as 91% of anxiety disorders surveys have shown effective results in treating. However, there is still disagreement regarding the effect of exercise compared to the use of antidepressant symptoms and cognitive function in anxiety, this suggests that there is no consensus on the correct intensity of aerobic exercise as to achieve the best dose-response, with intensities high to moderate or moderate to mild. PMID- 26556090 TI - Comparison Among Aerobic Exercise and Other Types of Interventions to Treat Depression: A Systematic Review. AB - Depression is a common and disabling disease that affects over 100 million people worldwide and can have a significant impact on physical and mental health, reducing their quality of life. Thus, the aim of this article was to provide information on research results and key chains related to the therapeutic effects of chronic aerobic exercise compared with other types of interventions to treat depression, which may become a useful clinical application in a near future. Researches have shown the effectiveness of alternative treatments, such as physical exercise, minimizing high financial costs and minimizing side effects. In this review, the data analyzed allows us to claim that alternative therapies, such as exercise, are effective on controlling and reducing symptoms. 69.3% of the studies that investigated the antidepressant effects of exercise on depressive were significant, and the other 30.7% of the studies improved only in general physiological aspects, such as increased oxygen uptake, increased use of blood glucose and decreased body fat percentage, with no improvement on symptoms of depression. From the sample analyzed, 71.4% was composed of women, and regarding the severity of symptoms, 85% had mild to moderate depression and only 15% had moderate to severe depression. However, there is still disagreement regarding the effect of exercise compared to the use of antidepressants in symptomatology and cognitive function in depression, this suggests that there is no consensus on the correct intensity of aerobic exercise as to achieve the best dose-response, with intensities high to moderate or moderate to mild. PMID- 26556091 TI - Wii Balance Board: Reliability and Clinical Use in Assessment of Balance in Healthy Elderly Women. AB - Force plate is considered gold standard tool to assess body balance. However the Wii Balance Board (WBB) platform is a trustworthy equipment to assess stabilometric components in young people. Thus, we aim to examine the reliability of measures of center of pressure with WBB in healthy elderly women. Twenty one healthy and physically active women were enrolled in the study (age: 64 +/- 7 years; body mass index: 29 +/- 5 kg/m2. The WBB was used to assess the center of pressure measures in the individuals. Pressure was linearly applied to different points to test the platform precision. Three assessments were performed, with two of them being held on the same day at a 5- to 10-minute interval, and the third one was performed 48 h later. A linear regression analysis was used to find out linearity, while the intraclass correlation coefficient was used to assess reliability. The platform precision was adequate (R2 = 0.997, P = 0.01). Center of pressure measures showed an excellent reliability (all intraclass correlation coefficient values were > 0.90; p < 0.01). The WBB is a precise and reliable tool of body stability quantitative measure in healthy active elderly women and its use should be encouraged in clinical settings. PMID- 26556092 TI - Wii-Workouts on Chronic Pain, Physical Capabilities and Mood of Older Women: A Randomized Controlled Double Blind Trial. AB - Chronic Low Back Pain (CLBP) is a public health problem and older women have higher incidence of this symptom, which affect body balance, functional capacity and behavior. The purpose of this study was to verifying the effect of exercises with Nintendo Wii on CLBP, functional capacity and mood of elderly. Thirty older women (68 +/- 4 years; 68 +/- 12 kg; 154 +/- 5 cm) with CLBP participated in this study. Elderly individuals were divided into a Control Exercise Group (n = 14) and an Experimental Wii Group (n = 16). Control Exercise Group did strength exercises and core training, while Experimental Wii Group did ones additionally to exercises with Wii. CLBP, balance, functional capacity and mood were assessed pre and post training by the numeric pain scale, Wii Balance Board, sit to stand test and Profile of Mood States, respectively. Training lasted eight weeks and sessions were performed three times weekly. MANOVA 2 x 2 showed no interaction on pain, siting, stand-up and mood (P = 0.53). However, there was significant difference within groups (P = 0.0001). ANOVA 2 x 2 showed no interaction for each variable (P > 0.05). However, there were significant differences within groups in these variables (P < 0.05). Tukey's post-hoc test showed significant difference in pain on both groups (P = 0.0001). Wilcoxon and Mann-Whitney tests identified no significant differences on balance (P > 0.01). Capacity to Sit improved only in Experimental Wii Group (P = 0.04). In conclusion, physical exercises with Nintendo Wii Fit Plus additional to strength and core training were effective only for sitting capacity, but effect size was small. PMID- 26556093 TI - [Obituary for Prof. Dr. Stavros Mentzos (1930-2015)]. PMID- 26556094 TI - ["Time is brain" in relapsing remitting multiple sclerosis. Current treatment concepts in immunotherapy]. AB - BACKGROUND: Despite highly divergent time scales of disease evolution in multiple sclerosis (MS) and ischemic stroke, clear analogies are apparent that may point the way to optimization of MS treatment. Inflammatory disease activity and neurodegeneration may induce potentially irreversible damage to central nervous system structures and thus lead to permanent disability. For the treatment of MS early detection of disease activity and early immunotherapy or treatment optimization are pivotal determinants of long-term outcomes. Such therapeutic concepts may be described with the catchy phrase "time is brain" as coined for the acute thrombolytic treatment of ischemic stroke. RESULTS AND DISCUSSION: For MS a "time is brain" concept would comprise an early initiation of first line therapy as well as sensitive and structured monitoring of disease activity under therapy in conjunction with a low threshold for timely treatment optimization to achieve sustained freedom from measurable disease activity. This approach may substantially improve the long-term outcome in patients who show insufficient response to platform therapies. The intersectorial collaboration in regional MS care networks involving office-based neurologists and specialized MS centers may facilitate the timely use of highly active therapies with their specific benefit risk profiles thus supporting sustained stabilization of patient quality of life. PMID- 26556096 TI - [Reperfusion of the artery of Percheron by mechanical recanalization of the posterior cerebral artery]. PMID- 26556095 TI - [Admission and discharge decisions in psychiatric hospitals : The 7-day cycle: analysis based on the VIPP database]. AB - BACKGROUND: The legislation requires all scientific societies in the field of inpatient psychiatric and psychosomatic healthcare to survey and assess the effects and financial incentives of the new flat rate day-based remuneration system in psychiatric and psychosomatic facilities (PEPP system). As day-based remuneration systems may be an incentive to extend treatment, it is necessary to measure and analyze the future development of the number of cases and the duration of treatment. OBJECTIVES: This article surveys admission and discharge decisions of psychiatric and psychosomatic facilities. The distribution of admissions and discharges throughout the days of the week were analyzed to search for evidence of a systematic extension of treatment over the weekend. MATERIAL AND METHODS: The analysis is based on data from the Versorgungsrelevante Indikatoren in der Psychiatrie und Psychosomatik (VIPP, treatment-relevant indicators in psychiatry and psychosomatics) project database, which contains routine data from psychiatric and psychosomatic facilities. On this basis the distributions of admissions and discharges throughout the days of the week were analyzed on aggregate and diagnosis-specific levels. RESULTS: Patients were mostly admitted to hospitals within the first 3 weekdays. The discharge mostly took place on Fridays and not as a financial incentive on Mondays. Regarding the patient length of stay a 7-day cycle can be observed, which may indicate the importance of medical and organizational factors in discharge decisions. CONCLUSION: The results do not show evidence for a systematic extension of treatment over the weekend. Over the next years it will be important to observe the development of the duration of treatment and the number of cases to assess the influence of the economic incentives of the PEPP system on the utilization of psychiatric and psychosomatic healthcare. PMID- 26556097 TI - Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. AB - BACKGROUND: In randomized, controlled, double-blind, multicenter phase 3 studies, one icatibant injection was efficacious and generally well tolerated in patients with a single hereditary angioedema (HAE) attack. Here, the efficacy and safety of icatibant for multiple HAE attacks was evaluated across the controlled and open-label extension phases of the For Angioedema Subcutaneous Treatment (FAST)-3 study (NCT00912093). METHODS: In the controlled phase, adults with HAE type I or II were randomized (1:1) to receive a single subcutaneous injection of icatibant 30 mg or placebo within 6 h of an attack becoming mild (laryngeal) or moderate (cutaneous/abdominal). Open-label icatibant was administered for severe laryngeal symptoms. In the open-label extension phase, patients could receive up to three icatibant injections per attack. Efficacy and safety were analyzed for the first five icatibant-treated attacks at any location (prospective analysis) and laryngeal attacks (post hoc analysis) across both phases. Efficacy outcomes were based on patient-reported symptom severity (visual analog scale). RESULTS: In groups of patients with one to five icatibant-treated attacks at any location (n = 88), the median times to onset of symptom relief, onset of primary symptom relief and almost complete symptom relief were 1.9-2.1, 1.5-2.0 and 3.5-19.7 h, respectively. The same outcomes for laryngeal attacks (n = 25) were 1.0-2.0, 1.0 2.0 and 1.5-8.1 h, respectively. The most frequently reported adverse events were a worsening or recurrence of HAE attack, headache and nasopharyngitis. Two serious adverse events (arrhythmia and noncardiac chest pain) were considered to be related to icatibant. CONCLUSIONS: Icatibant was efficacious and generally well tolerated across multiple HAE attacks, including laryngeal attacks. PMID- 26556098 TI - Developing a Novel Gene-Delivery Vector System Using the Recombinant Fusion Protein of Pseudomonas Exotoxin A and Hyperthermophilic Archaeal Histone HPhA. AB - Non-viral gene delivery system with many advantages has a great potential for the future of gene therapy. One inherent obstacle of such approach is the uptake by endocytosis into vesicular compartments. Receptor-mediated gene delivery method holds promise to overcome this obstacle. In this study, we developed a receptor mediated gene delivery system based on a combination of the Pseudomonas exotoxin A (PE), which has a receptor binding and membrane translocation domain, and the hyperthermophilic archaeal histone (HPhA), which has the DNA binding ability. First, we constructed and expressed the rPE-HPhA fusion protein. We then examined the cytotoxicity and the DNA binding ability of rPE-HPhA. We further assessed the efficiency of transfection of the pEGF-C1 plasmid DNA to CHO cells by the rPE HPhA system, in comparison to the cationic liposome method. The results showed that the transfection efficiency of rPE-HPhA was higher than that of cationic liposomes. In addition, the rPE-HPhA gene delivery system is non-specific to DNA sequence, topology or targeted cell type. Thus, the rPE-HPhA system can be used for delivering genes of interest into mammalian cells and has great potential to be applied for gene therapy. PMID- 26556099 TI - Mechanism of Thermal Adaptation in the Lactate Dehydrogenases. AB - The mechanism of thermal adaptation of enzyme function at the molecular level is poorly understood but is thought to lie within the structure of the protein or its dynamics. Our previous work on pig heart lactate dehydrogenase (phLDH) has determined very high resolution structures of the active site, via isotope edited IR studies, and has characterized its dynamical nature, via laser-induced temperature jump (T-jump) relaxation spectroscopy on the Michaelis complex. These particular probes are quite powerful at getting at the interplay between structure and dynamics in adaptation. Hence, we extend these studies to the psychrophilic protein cgLDH (Champsocephalus gunnari; 0 degrees C) and the extreme thermophile tmLDH (Thermotoga maritima LDH; 80 degrees C) for comparison to the mesophile phLDH (38-39 degrees C). Instead of the native substrate pyruvate, we utilize oxamate as a nonreactive substrate mimic for experimental reasons. Using isotope edited IR spectroscopy, we find small differences in the substate composition that arise from the detailed bonding patterns of oxamate within the active site of the three proteins; however, we find these differences insufficient to explain the mechanism of thermal adaptation. On the other hand, T jump studies of reduced beta-nicotinamide adenine dinucleotide (NADH) emission reveal that the most important parameter affecting thermal adaptation appears to be enzyme control of the specific kinetics and dynamics of protein motions that lie along the catalytic pathway. The relaxation rate of the motions scale as cgLDH > phLDH > tmLDH in a way that faithfully matches kcat of the three isozymes. PMID- 26556100 TI - Integration of Visual and Olfactory Cues in Host Plant Identification by the Asian Longhorned Beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae). AB - Some insects use host and mate cues, including odor, color, and shape, to locate and recognize their preferred hosts and mates. Previous research has shown that the Asian longicorn beetle, Anoplophora glabripennis (Motschulsky), uses olfactory cues to locate host plants and differentiate them from non-host plants. However, whether A. glabripennis adults use visual cues or a combination of visual and olfactory cues remains unclear. In this study, we tested the host location and recognition behavior in A. glabripennis, which infests a number of hardwood species and causes considerable economic losses in North America, Europe and Asia. We determined the relative importance of visual and olfactory cues from Acer negundo in host plant location and recognition, as well as in the discrimination of non-host plants (Sabina chinensis and Pinus bungeana), by female and male A. glabripennis. Visual and olfactory cues from the host plants (A. negundo), alone and combined, attracted significantly more females and males than equivalent cues from non-host plants (S. chinensis and P. bungeana). Furthermore, the combination of visual and olfactory cues of host plants attracted more adults than either cue alone, and visual cues alone attracted significantly more adults than olfactory cues alone. This finding suggests that adult A. glabripennis has an innate preference for the visual and/or olfactory cues of its host plants (A. negundo) over those of the non-host plant and visual cues are initially more important than olfactory cues for orientation; furthermore, this finding also suggests that adults integrate visual and olfactory cues to find their host plants. Our results indicate that different modalities of host plant cues should be considered together to understand fully the communication between host plants and Asian longhorned beetles. PMID- 26556101 TI - Antiplatelet effects of clopidogrel and aspirin after interventional patent foramen ovale/ atrium septum defect closure. AB - The optimal antiplatelet therapy after patent foramen ovale (PFO)/ atrium septum defect (ASD) closure is a matter of discussion. It is challenging as inter individual responses to antiplatelet medication vary significantly and common complications are bleeding and ischemic events. In this study, we aimed to analyze the incidence of high on-treatment platelet reactivity (HTPR) to antiplatelet medication in patients undergoing PFO/ASD closure as well as clinical complications and thrombus formation on the occluder during six-month follow-up. This hypothesis generating pilot study was observed, which included 140 patients undergoing PFO/ASD closure. The primary endpoint was pharmacodynamic response to antiplatelet medication. A composite of death, myocardial infarction, bleeding, stroke and thrombus formation on the occluder during six-month follow up was the secondary endpoint. HTPR to clopidogrel was analyzed using the vasodilator-stimulated protein phosphorylation (VASP), HTPR to aspirin by light transmission aggregometry (LTA). In 71% of patients HTPR to clopidogrel was detected, HTPR to aspirin in only 4%. We observed 12 complications, 9 bleeding events (including 3 major bleeding events) and 3 transient ischemic attacks. No stroke and no thrombus formation on the occluder occurred. The primary endpoint was not associated with the secondary endpoint. The incidence of HTPR to clopidogrel in PFO/ASD closure patients is very high. Despite this high incidence, no stroke or thrombus formation on the occluder occurred at all. This leads to the hypothesis, that the benefit of additional clopidogrel medication is questionable and has to be investigated in large-scale clinical trials. PMID- 26556102 TI - Very High Brightness Quantum Dot Light-Emitting Devices via Enhanced Energy Transfer from a Phosphorescent Sensitizer. AB - We demonstrate very efficient and bright quantum dot light-emitting devices (QDLEDs) with the use of a phosphorescent sensitizer and a thermal annealing step. Utilizing CdSe/CdS core/shell quantum dots with 560 nm emission peak, bis(4,6-difluorophenylpyridinatoN,C2) picolinatoiridium as a sensitizer, and thermal annealing at 50 degrees C for 30 min, green-emitting QDLEDs with a maximum current efficiency of 23.9 cd/A, a power efficiency of 31 lm/W, and a brightness of 65,000 cd/m(2) are demonstrated. The high efficiency and brightness are attributed to annealing-induced enhancements in both the Forster resonance energy transfer (FRET) process from the phosphorescent energy donor to the QD acceptor and hole transport across the device. The FRET enhancement is attributed to annealing-induced diffusion of the phosphorescent material molecules from the sensitizer layer into the QD layer, which results in a shorter donor-acceptor distance. We also find, quite interestingly, that FRET to a QD acceptor is strongly influenced by the QD size, and is generally less efficient to QDs with larger sizes despite their narrower bandgaps. PMID- 26556103 TI - Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review. AB - The aim of this study was to review the cytokine profiles in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMJD). Databases were searched from 1965 till September 2015 using different combinations of the following key words: "Temporomandibular joint"; "Cytokine"; "disorder"; and "synovial fluid" and "inflammation". Titles and abstracts of studies identified using the above-described protocol were screened and checked for agreement. Full texts of articles judged by title and abstract to be relevant were read and independently evaluated. Hand-searching of the reference lists of potentially relevant original and review articles was also performed. The pattern of the present systematic review was customized to mainly summarize the relevant data. Fifteen studies were included. In 12 studies, cytokine profile of patients with TMJD was assessed using enzyme linked immunosorbent assay; and in 2 studies, histological analysis was performed to assess the cytokine profile of patients with TMJD. Patients with TMJD presented raised levels of interleukin (IL)-6 in 8 studies, IL-1beta (1beta) in 5 studies and tumor necrosis factor-alpha (TNF alpha) in 5 studies. Two studies showed no significant difference in TNF-alpha levels in patients with and without TMJD; and IL-1beta levels were comparable in patients with and without TMJD in 2 studies. Raised levels of IL-6, TNF-alpha, IL 1beta, IL-8, and IFN-gamma in the SF have been associated with inflammation in patients with TMJD. Cytokines IL-10, osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG), and VEGF found in the SF of TMJs could have an anti-inflammatory effect. PMID- 26556104 TI - Proinflammatory cytokine interleukin-1beta suppresses cold-induced thermogenesis in adipocytes. AB - In this study, we investigated the effects of interleukin-1beta (IL-1beta), a typical proinflammatory cytokine on the beta-adrenoreceptor-stimulated induction of uncoupling protein 1 (UCP1) expression in adipocytes. IL-1beta mRNA expression levels were upregulated in white adipose tissues of obese mice and in RAW264.7 macrophages under conditions designed to mimic obese adipose tissue. Isoproterenol-stimulated induction of UCP1 mRNA expression was significantly inhibited in C3H10T1/2 adipocytes by conditioned medium from lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in comparison with control conditioned medium. This inhibition was significantly attenuated in the presence of recombinant IL-1 receptor antagonist and IL-1beta antibody, suggesting that activated macrophage-derived IL-1beta is an important cytokine for inhibition of beta-adrenoreceptor-stimulated UCP1 induction in adipocytes. IL-1beta suppressed isoproterenol-induced UCP1 mRNA expression in C3H10T1/2 adipocytes, and this effect was partially but significantly abrogated by inhibition of extracellular signal-regulated kinase (ERK). IL-1beta also suppressed the isoproterenol-induced activation of the UCP1 promoter and transcription factors binding to the cAMP response element. Moreover, intraperitoneal administration of IL-1beta suppressed cold-induced UCP1 expression in adipose tissues. These findings suggest that IL 1beta upregulated in obese adipose tissues suppresses beta-adrenoreceptor stimulated induction of UCP1 expression through ERK activation in adipocytes. PMID- 26556105 TI - Majoon ushba, a polyherbal compound ameliorates rheumatoid arthritis via regulating inflammatory and bone remodeling markers in rats. AB - The present study was aimed to investigate the anti-arthritic effect of majoon ushba (MU) and its underlying mechanism in adjuvant induced arthritis (AIA) rats. Arthritis was induced by intradermal injection of complete freund's adjuvant (0.1ml) into the right hind paw of the Wistar albino rats. MU (1000mg/kg/b.wt) and methotrexate (3mg/kg/b.wt) were administered from day 11 to day 18th for 8days after adjuvant induction. We have found that MU treatment significantly increased the level of anti-inflammatory cytokine (IL-10) and inhibited the over production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and monocyte chemoattractant protein-1 (MCP-1) (ELISA) in the serum of adjuvant induced arthritic rats. The mRNA expression of pro-inflammatory cytokines (TNF alpha, IL-1beta, IL-6, and IL-17), inflammatory enzymes (inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2)), MCP-1, receptor activator of nuclear factor-kB ligand (RANKL) and transcription factors (NF-kB and AP-1) (Real Time PCR) was found significantly downregulated in the synovial tissues of MU treated arthritic rats. In addition, the protein expression of NF-kB, IL-17, COX 2, and RANKL (western blotting and immunohistochemistry analysis) was found reduced. On the other hand, osteoprotegerin (OPG), a bone remodeling marker was found to be elevated in synovial tissues of MU treated arthritic rats. Furthermore, MU treatment prevented body weight loss and reduced the joint paw edema, cell infiltration, cartilage and bone degradation as evidenced by the histopathological and radiological analysis. In conclusion, our current findings provide scientific evidence for the traditional claim of MU as an anti-arthritic drug. PMID- 26556107 TI - Blood-Conservation Strategies in a Blood-Refusal Parturient with Placenta Previa and Placenta Percreta. AB - Abnormal placentation can be associated with significant blood loss and massive blood transfusions. Caring for parturients with abnormal placentation who refuse blood transfusion is very challenging. We present a 35-year-old, gravida 3, para 1, Jehovah's Witness at 35 weeks of gestation with placenta percreta, who underwent cesarean delivery and delayed hysterectomy. A multidisciplinary team developed a plan, including the use of perioperative erythropoietin and IV iron dextran, intraoperative acute normovolemic hemodilution, cell salvage, tranexamic acid, and uterine artery embolization. This strategy was successful in avoiding the need for allogeneic transfusion and ensuring an uneventful recovery after both surgical procedures. PMID- 26556106 TI - Argatroban in the management of heparin-induced thrombocytopenia: a multicenter clinical trial. AB - INTRODUCTION: The aim of this study was to collect data in France in patients with heparin-induced thrombocytopenia who required parenteral anticoagulation and for whom other non-heparin anticoagulant therapies were contraindicated including patients with renal failure, cross-reactivity to danaparoid or at high hemorrhagic risk. METHODS: A total of 20 patients, of mean age 72 +/- 10 years, were enrolled in this open-label, multicenter clinical study. Exploratory statistical data analysis was performed with descriptive interpretation of intra individual comparisons using simple univariate statistics. RESULTS: The diagnosis of HIT was confirmed in 16 subjects by an independent scientific committee. Fourteen patients (70 %) were in an intensive care unit during the course of the study. Patients were treated with argatroban for a mean duration of 8.5 +/- 6.1 days. The mean starting dose of argatroban was 0.77 +/- 0.45 MUg/kg/min. Platelet recovery was rapid. aPTT and anti-IIa activity assays were used to monitor the dose of argatroban. The mean baseline aPTT value was 45.0 +/- 9.8 sec and increased to 78.2 +/- 35.8 sec two hours after initiating argatroban. At this time mean argatroban concentration was 0.34 +/- 0.16 and 0.61 +/- 0.28 MUg/ml using ECT and TT measurements, respectively. New and/or extended thromboses were reported in 25 % of patients and major bleedings were documented in 15 %. Six patients died due to their underlying medical condition. CONCLUSION: Considering its hepatic elimination and its short half-life, argatroban can be considered as a safe therapeutic option in HIT patients at high hemorrhagic risk and with renal failure, particularly in an ICU setting. PMID- 26556108 TI - The Critical Importance of Hepatic Venous Blood Flow Doppler Assessment for Patients in Shock. AB - Hepatic venous blood flow can be easily obtained using bedside ultrasound with either transthoracic or transesophageal echocardiography. Six critically ill patients with shock associated with absent or significantly reduced hepatic venous blood flow in the presence of normal or increased pulmonary venous flow are presented. In all these patients, the etiology of shock was secondary to increased resistance to venous return from either an intraabdominal process or through extrinsic or intrinsic occlusion of the proximal inferior vena cava or right atrium. These shock situations are secondary to increased resistance to venous return. Their treatment is highly specific and typically involves a surgical intervention. PMID- 26556109 TI - Prophylactic Antibiotic Management of Surgical Patients Noted as "Allergic" to Penicillin at Two Academic Hospitals. AB - We studied prophylactic antibiotics administered at 2 academic medical centers during a 6-year period where a cephalosporin was indicated but an "allergy" to penicillin was noted. Another drug (typically vancomycin or clindamycin) was substituted approximately 80% of the time; this occurred frequently even when symptoms unrelated to acute hypersensitivity were listed. In >50% of cases, the reaction was either omitted or vague (e.g., simply "rash"). Given the estimated 1% cross-reactivity between penicillins and cephalosporins with similar R1 side chains, many of these patients could have received either the prescribed cephalosporin or another cephalosporin with a different R1 side chain. PMID- 26556110 TI - The Effect of Peribulbar Block with General Anesthesia for Vitreoretinal Surgery in Premature and Ex-Premature Infants with Retinopathy of Prematurity. AB - Safe anesthesia in premature and ex-premature infants remains a challenge for the anesthesiologist. These infants are at risk of postoperative apnea, desaturation, and bradycardia after general anesthesia. We describe our experience of peribulbar block in 24 infants who underwent vitreoretinal surgery for retinopathy of prematurity. None of our patients had postoperative apnea or required neonatal intensive care admission. A possible opioid and muscle relaxant sparing effect of peribulbar block might have reduced the incidence of postoperative complications. PMID- 26556113 TI - Contrast enhanced Voiding Urosonography (ce-VUS) as a radiation-free technique in the diagnosis of vesicoureteric reflux: Our early experience. AB - OBJECTIVE: Contrast-enhanced ultrasound has become increasingly utilised as an alternative imaging modality for the diagnosis of vesicoureteric reflux (VUR) in paediatric patients. The study objective is to evaluate the efficacy of contrast enhanced Voiding Urosonography (ce-VUS) compared with fluoroscopic micturating cystourethrography (MCU) in the detection of VUR. METHODS: This prospective study was carried out between July 2011 and January 2013 on paediatric patients who underwent MCU. All consented patients would undergo ce- VUS prior to MCU. We documented the epidemiology details, the number of Kidney-Ureter (K-U) unit studied, baseline renal and bladder sonogram, as well as presence of VUR on ce VUR. The technique for ce-VUS was standardized using normal saline to fill the bladder prior to administration of SonoVue(r) (2.5 ml) to assess the kidney ureter (K-U) unit. Dedicated contrast detection software was used to discern the presence of microbubbles in the pelvicaliceal system (PCS). The findings were then compared with MCU. RESULTS: 27 paediatric patients were involved in the study [17 males (63%) and 10 females (37%)] involving 55 K-U units (one patient had a complete duplex system). MCU detected VUR in 10 K-U units while ce-VUS detected VUR in 8 out of the 10 K-U units. There were 2 false negative cases (both Grade 1) with ce-VUS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of ce-VUS were 80%, 98%, 95%, 89% and 96%, respectively. CONCLUSION: ce-VUS is a sensitive and specific radiation free alternative for the detection of VUR in the paediatric population. PMID- 26556114 TI - Causes of mortality in patients with psoriasis in Malaysia - Evidence from the Malaysian Psoriasis Registry. AB - BACKGROUND: Patients with severe psoriasis, namely those requiring phototherapy or systemic treatment, have an increased risk of death. The aim of this study was to determine the prevalence, aetiology and risk factors for mortality among adult patients aged 18 years and above with psoriasis in Malaysia. METHODS: This was a retrospective study involving adult patients notified by dermatologists to the Malaysian Psoriasis Registry between July 2007 and December 2013. Data were cross checked against the National Death Registry. Patients certified dead were identified and the cause of death was analysed. Multivariate analysis using multiple logistic regression were conducted on potential factors associated with higher risk of mortality. RESULTS: A total of 419 deaths were identified among the 9775 patients notified. There were four significant risk factors for higher mortality: age>40 years (age 41-60 years old, Odds Ratio (OR) 2.70, 95%CI 1.75, 4.18; age>60 years OR 7.46, 95%CI 4.62, 12.02), male gender (OR 1.72, 95%CI 1.33,2.22), severe psoriasis with body surface area (BSA) >10% (OR 1.52, 95%CI 1.19, 1.96) and presence of at least one cardiovascular co-morbidity (OR 1.67, 95% CI 1.30, 2.14). Among the 301 patients with verifiable causes of death, the leading causes were infection (33.9%), cardiovascular disease (33.6%) and malignancy (15.9%). CONCLUSION: Infection was the leading cause of death among psoriasis patients in Malaysia. Although cardiovascular diseases are well-known to cause significant morbidity and mortality among psoriasis patients, the role of infections and malignancy should not be overlooked. PMID- 26556112 TI - Fabrication of a Bioactive, PCL-based "Self-fitting" Shape Memory Polymer Scaffold. AB - Tissue engineering has been explored as an alternative strategy for the treatment of critical-sized cranio-maxillofacial (CMF) bone defects. Essential to the success of this approach is a scaffold that is able to conformally fit within an irregular defect while also having the requisite biodegradability, pore interconnectivity and bioactivity. By nature of their shape recovery and fixity properties, shape memory polymer (SMP) scaffolds could achieve defect "self fitting." In this way, following exposure to warm saline (~60 oC), the SMP scaffold would become malleable, permitting it to be hand-pressed into an irregular defect. Subsequent cooling (~37 oC) would return the scaffold to its relatively rigid state within the defect. To meet these requirements, this protocol describes the preparation of SMP scaffolds prepared via the photochemical cure of biodegradable polycaprolactone diacrylate (PCL-DA) using a solvent-casting particulate-leaching (SCPL) method. A fused salt template is utilized to achieve pore interconnectivity. To realize bioactivity, a polydopamine coating is applied to the surface of the scaffold pore walls. Characterization of self-fitting and shape memory behaviors, pore interconnectivity and in vitro bioactivity are also described. PMID- 26556115 TI - Port assisted closure of laparoscopic wound: A safe and feasible technique. AB - OBJECTIVE: Various techniques and instruments have been developed to provide safe and secure closure of laparoscopic wounds. Herein we describe a simple method to close laparoscopic supraumbilical wounds with the aid of a laparoscopic port. METHOD: This was a retrospective review of prospective data, which were from 151 patients who underwent laparoscopic cholecystectomy for symptomatic gallstone disease from December 2009 to December 2010 in Sultanah Bahiyah Hospital. A senior consultant hepato-pancreato-biliary (HPB) surgeon and two HPB trainee surgeons performed the operations. Postoperatively, all patients were followed up at 4 weeks. RESULTS: All patients successfully underwent closure of the supraumbilical wound with the assistance of a 5mm laparoscopic port. None of the patients had incisional hernia on follow up. CONCLUSION: Port assisted closure of supraumbilical laparoscopic wounds is a feasible and safe technique. PMID- 26556116 TI - Treating hepatitis C in HIV/HCV co-infected patients in Malaysia - the outcomes and challenges. AB - BACKGROUND: Co-infection by human immunodeficiency and hepatitis C viruses (HIV/HCV) is common and results in significant morbidity and mortality despite effective antiretroviral therapies (ART). METHOD: A retrospective and prospective evaluation of the efficacy and safety of pegylated interferon alfa 2a/2b plus ribavirin (PEG-IFN/RBV) in consecutive HIV/HCV co-infected patients treated in real life clinical practice in Malaysia. RESULTS: Forty-five HIV/HCV co-infected patients with a median age (interquartile range, IQR) of 41 years (37; 47) were assessed for treatment with PEG-IFN/RBV. All except one are of male gender and the most common risk behaviour was injecting drug use. At baseline 75.5% was on ART and the median (IQR) CD4 count was 492 cells/MUl (376; 621). The HCV genotypes (GT) were 73 % GT3 and 27% GT1. Liver biopsies in forty patients showed 10% had liver cirrhosis and another 50% had significant liver fibrosis. The treatment completion rate was 79.5% with 15.9% dropped out of treatment due to adverse effects (AE) or default and 4.6% due to lack of early virological response. The AE causing premature discontinuations were neuropsychiatric and haematological. The overall sustained virological response (SVR) was 63.6% with a trend towards higher SVR in GT3 compared with GT1 (71.9% vs. 41.7%; p=0.064). In patients with bridging fibrosis plus occasional nodules or cirrhosis on liver biopsy, the SVR was significantly lower at 20% (p=0.030) compared to those with milder fibrosis. CONCLUSION: HIV/HCV co-infected patients can be successfully and safely treated with PEG-IFN/RBV achieving high rates of SVR except in cirrhotic patients. PMID- 26556117 TI - Seroepidemiological study of leptospirosis among the communities living in periurban areas of Sarawak, Malaysia. AB - INTRODUCTION: Leptospirosis is endemic to tropical regions of the world and is re emerging as a new danger to public health in Malaysia. the purpose of this particular study was to determine the common leptospiral serovars present in human communities living around wildlife reserves/disturbed forest habitats. the objective of this study was to estimate the seroprevalence of leptospirosis and finding infecting serovars in villages surrounded habitats where wildlife lives in Sarawak, Malaysia. METHODS: A cross-sectional serological survey of 198 humans was conducted in four villages around Kuching, Sarawak between January 2011 and March 2012. RESULTS: A seroprevalence of 35.9% (95%cI 29.2-43.0) to the MAt was detected in the tested humans. Antibodies to serovar Lepto 175 Sarawak were most commonly detected (31.3%; 95%cI 24.9-38.3) and were detected in individuals at all four locations. the presence of skin wounds (Or 3.1), farm animals (Or 2.5) and rats (Or 11.2) were all significantly associated with seropositivity in a multivariable logistic regression model. CONCLUSIONS: the results of the current study are important as wildlife may act as reservoirs of leptospires for humans. Health authorities should expand disease control measures to minimise the spill over from wildlife to humans visiting, living or working in the sampled locations. the pathogenic status of serovar Lepto 175 Sarawak also requires further investigation. PMID- 26556118 TI - Parents' perspectives on the important aspects of care in children dying from life limiting conditions: A qualitative study. AB - INTRODUCTION: The importance of Paediatric Palliative Care (PPC) is increasingly recognised worldwide, with the World Health Organzsation (WHO) and the American Academy of Pediatrics (AAP) endorsing the development and wide availability of PPC. When these children are in the terminal phase of their illness, PPC should be tailored to the different needs and desires of the child and the family, with the goal of providing the best possible quality of life (QOL) for the days that remain. METHOD: Malaysia has yet to develop a national PPC policy. In anticipation of this, as part of a needs based qualitative study, parents' views were solicited, as to the unmet needs of their children during the terminal phases of their illness. A purposive sampling was conducted amongst fifteen parents of nine deceased children (ages 2-14 years, eight cancer, one Prader Willi Syndrome) who had received care in the Paediatric Department, Malacca General Hospital, a Malaysian government hospital. Two focus group discussions and three in-depth interviews were conducted, based on a semi-structured interview guideline. The interviews were audiotaped with permission and the tape recordings were transcribed verbatim. The data were managed and analysed by NVivo 9 software using a thematic analysis approach. RESULTS: The frequently emerging themes were the strengths and weaknesses pertaining to the healthcare system, processes within palliative care. These were symptom control, closed communication and lack of support and anticipatory guidance as death approached. CONCLUSION: Dying Malaysian children and their families deserve to receive care that is more consistent with optimal palliative care. PMID- 26556119 TI - Improving the self-confidence level of medical undergraduates during emergencies using high fidelity simulation. AB - INTRODUCTION: Medical practice involves routinely making critical decisions regarding patient care and management. Many factors influence the decision-making process, and self-confidence has been found to be an important factor in effective decision-making. With the proper transfer of knowledge during their undergraduate studies, selfconfidence levels can be improved. The purpose of this study was to evaluate the use of High Fidelity Simulation as a component of medical education to improve the confidence levels of medical undergraduates during emergencies. METHODOLOGY: Study participants included a total of 60 final year medical undergraduates during their rotation in Medical Senior Posting. They participated in a simulation exercise using a high fidelity simulator, and their confidence level measured using a self-administered questionnaire. RESULTS: The results found that the confidence levels of 'Assessment of an Emergency Patient', 'Diagnosing Arrhythmias', 'Emergency Airway Management', 'Performing Cardio pulmonary Resuscitation', 'Using the Defibrillator' and 'Using Emergency Drugs' showed a statistically significant increase in confidence levels after the simulation exercise. The mean confidence levels also rose from 2.85 to 3.83 (p<0.05). CONCLUSION: We recommend further use of High Fidelity Simulation in medical education to improve the confidence levels of medical undergraduates. PMID- 26556120 TI - Depression among chronic pain patients at Hospital Tengku Ampuan Rahimah, Klang. AB - INTRODUCTION: Despite the high prevalence rates of depression amongst chronic pain patients reported globally, the condition is often under-recognised and under-treated. Depression frequently complicates the effective management of pain and is associated with poor quality of life. This study aimed to explore the incidence of depression and its' associated factors in a sample of chronic pain patients in Malaysia. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted amongst clinically diagnosed chronic pain patients from the pain management clinic of Hospital Tengku Ampuan Rahimah over a period of seven months. Socio-demographics and clinical data were obtained from patients' interview and medical records. The validated Depression Anxiety Stress Scale-21 (DASS-21) was used for screening and Mini International Neuropsychiatric Interview (MINI) was used to establish the depression diagnoses among the patients. Numeric pain intensity scale was used to assess the severity of pain. RESULTS: Eighty-three patients with a mean age of 50.4+/-12.50 years participated in this study. The majority of the patients were females (56.6%), married (85.5%) and being employed (49.4%). The percentage of depression was 37.4%. Depression was significantly associated with severity of pain (p<0.001) and the duration of pain (p <0.05). CONCLUSION: Almost one third of chronic pain patients in this study have depression. Depression was significantly associated with the severity and duration of pain. Depression should be regularly screened among patient with chronic pain. PMID- 26556121 TI - Knowledge, attitude and practice of antibiotics prescribing among medical officers of public health care facilities in the state of Kedah, Malaysia. AB - BACKGROUND: Antibiotic resistance is a rising problem in Malaysia. For instance, high antibiotic prescribing rate for upper respiratory tract infection and inappropriate choice of antibiotic is a significant healthcare concern in Malaysia. Our main objective was to study knowledge, attitude and practice of antibiotic prescribing among medical officers in Kedah, Malaysia. METHODS: A cross sectional study was conducted in outpatient departments of health clinics and hospitals in Kedah from June 2013 until December 2013. Sample size was 118 and systematic sampling was conducted. Research tool used was a validated questionnaire from studies conducted in Congo and Peru. RESULTS: Response rate was 84.8%. Majority of our respondents were female doctors (71.0%), local graduates (63.0%), and practiced for 4 years or less (61.0%). 52.0% of the respondents prescribed antibiotics more than once daily. Mean knowledge score on antibiotics was 5.31 +/-1.19 (95% CI: 5.06; 5.54). More than half (62.0%) of our respondents were confident in antibiotic prescribing and there were merely 18.0% of them consulted any colleagues prior to prescription. There was a significant difference in frequency of antibiotic prescribing between junior doctors and senior doctors (P-value: 0.036). In addition, there was also a significant association between frequency of antibiotic prescribing and awareness of antibiotic resistance in their daily practice. (P-value: 0.002). CONCLUSION: Knowledge on antibiotic was moderate among our medical officers and antibiotic prescribing was frequent. Training and courses on appropriate antibiotic prescribing should be emphasized to ensure the best practice in antibiotic prescription. PMID- 26556122 TI - Wandering intrauterine contraceptive device: An unusual travel to the sigmoid colon. AB - Intrauterine contraceptive device (IUCD) is common choice for contraception. Migration of IUCD is one of the complications that are encountered. Here we report a case of IUCD migration to the sigmoid colon. A 39-year-old Malay lady carrying a copper T type of IUCD presented with missing thread then underwent examination under anaesthesia, proceeded to hysteroscopy but failed removal. Abdominal ultrasound detected it in the left lower quadrant of abdomen. She then underwent diagnostic laparoscopy where the device was found to be embedded in the sigmoid colon. Technical difficulty necessitated conversion to mini laparotomy and sigmoidotomy to remove the IUCD and the bowel closed primarily. IUCD is a relatively simple and safe contraceptive procedure but possible complications are bleeding and pain that usually co-exist, pelvic infection, expulsion and perforation. Investigations should be based on clinical suspicion and migrated IUCD in symptomatic patients should be surgically removed whereas, asymptomatic patients can be managed conservatively under certain circumstances. However in the presence of a concurrent pathology that requires exploration then retrieval of the migrated IUCD should be undertaken. PMID- 26556123 TI - Embryonal rhabdomyosarcoma of the middle ear presenting with aural polyp and facial nerve palsy. AB - Rhabdomyosarcoma is a rare tumour in the middle ear and mastoid cavity in children and the diagnosis is difficult. Repeated histological examination may be essential to confirm the diagnosis. We report a 6 year old boy with a left aural polyp, otorrhoea and facial nerve palsy who was initially thought to have otitis media and mastoiditis. He had polypectomy and the tissue taken for histopathology suggested an inflammatory condition. Subsequently he had mastoidectomy. Tissue taken during mastoidectomy was however reported as rhabdomyosarcoma. The child developed a cerebral abscess and eventually succumbed. A literature review of the disease, radiological findings, immunohistochemical features and treatment options is described. PMID- 26556124 TI - Orbital compartment syndrome in idiopathic orbital inflammatory disease: A case report. AB - Orbital compartment syndrome (OCS) is a visual threatening ocular emergency. We report a 50-year-old male with acute presentation of OCS, a rare manifestation of idiopathic orbital inflammatory disease. At presentation, high intraocular pressure was reduced by prompt lateral canthotomy and cantholysis. The disease responded to systemic steroids and treatment resulted in good visual outcome. Detail evaluation and early detection and treatment are mandatory to prevent permanent vision loss. PMID- 26556125 TI - Sharing a microbe with man's best friend: A case of canine streptococcal infection in a diabetic patient. AB - We report a case of a diabetic patient with an infected leg wound leading to septicemia and abscess formation in the contra-lateral leg due to Streptococcus canis. This organism belongs to the Lancefield group G and is more commonly found in dogs. It is often mistaken for Streptococcus dysgalactiae which is a human strain of streptococci. Infections in humans are not common and usually involve infected wounds or ulcers and the surrounding soft tissue. In most reported cases, patients had close contact with domestic dogs and a pre-existing wound as a portal of entry. Our patient recovered after surgical debridement and drainage of abscess together with antibiotics. This organism is sensitive to common antibiotics like penicillin, amoxycillin, cephalosporins and erythromycin. The incidence of infections due to Streptococcus canis may be under-reported as laboratories may just report an isolate as group G streptococcus. Susceptible patients with wounds or ulcers should be counselled on proper wound care and advised to avoid or minimise contact with the family dog. PMID- 26556126 TI - Innovative oral spray-dried Idebenone systems to improve patient compliance. AB - Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients' compliance. According to these considerations, our goal was to develop spray dried microparticles using a soluble beta-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV-Vis absorption, (1)H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance. PMID- 26556127 TI - Tensile strain-induced softening of iron at high temperature. AB - In weakly ferromagnetic materials, already small changes in the atomic configuration triggered by temperature or chemistry can alter the magnetic interactions responsible for the non-random atomic-spin orientation. Different magnetic states, in turn, can give rise to substantially different macroscopic properties. A classical example is iron, which exhibits a great variety of properties as one gradually removes the magnetic long-range order by raising the temperature towards its Curie point of TC degrees = 1043 K. Using first principles theory, here we demonstrate that uniaxial tensile strain can also destabilise the magnetic order in iron and eventually lead to a ferromagnetic to paramagnetic transition at temperatures far below TC degrees . In consequence, the intrinsic strength of the ideal single-crystal body-centred cubic iron dramatically weakens above a critical temperature of ~500 K. The discovered strain-induced magneto-mechanical softening provides a plausible atomic-level mechanism behind the observed drop of the measured strength of Fe whiskers around 300-500 K. Alloying additions which have the capability to partially restore the magnetic order in the strained Fe lattice, push the critical temperature for the strength-softening scenario towards the magnetic transition temperature of the undeformed lattice. This can result in a surprisingly large alloying-driven strengthening effect at high temperature as illustrated here in the case of Fe-Co alloy. PMID- 26556128 TI - Fluorescence Recovery after Merging a Droplet to Measure the Two-dimensional Diffusion of a Phospholipid Monolayer. AB - We introduce a new method to measure the lateral diffusivity of a surfactant monolayer at the fluid-fluid interface, called fluorescence recovery after merging (FRAM). FRAM adopts the same principles as the fluorescence recovery after photobleaching (FRAP) technique, especially for measuring fluorescence recovery after bleaching a specific area, but FRAM uses a drop coalescence instead of photobleaching dye molecules to induce a chemical potential gradient of dye molecules. Our technique has several advantages over FRAP: it only requires a fluorescence microscope rather than a confocal microscope equipped with high power lasers; it is essentially free from the selection of fluorescence dyes; and it has far more freedom to define the measured diffusion area. Furthermore, FRAM potentially provides a route for studying the mixing or inter diffusion of two different surfactants, when the monolayers at a surface of droplet and at a flat air/water interface are prepared with different species, independently. PMID- 26556129 TI - Maternal risk factors associated with lead, mercury and cadmium. PMID- 26556130 TI - Metabolic engineering of Corynebacterium glutamicum for the de novo production of ethylene glycol from glucose. AB - Development of sustainable biological process for the production of bulk chemicals from renewable feedstock is an important goal of white biotechnology. Ethylene glycol (EG) is a large-volume commodity chemical with an annual production of over 20 million tons, and it is currently produced exclusively by petrochemical route. Herein, we report a novel biosynthetic route to produce EG from glucose by the extension of serine synthesis pathway of Corynebacterium glutamicum. The EG synthesis is achieved by the reduction of glycoaldehyde derived from serine. The transformation of serine to glycoaldehyde is catalyzed either by the sequential enzymatic deamination and decarboxylation or by the enzymatic decarboxylation and oxidation. We screened the corresponding enzymes and optimized the production strain by combinatorial optimization and metabolic engineering. The best engineered C. glutamicum strain is able to accumulate 3.5 g/L of EG with the yield of 0.25 mol/mol glucose in batch cultivation. This study lays the basis for developing an efficient biological process for EG production. PMID- 26556131 TI - Modular and selective biosynthesis of gasoline-range alkanes. AB - Typical renewable liquid fuel alternatives to gasoline are not entirely compatible with current infrastructure. We have engineered Escherichia coli to selectively produce alkanes found in gasoline (propane, butane, pentane, heptane, and nonane) from renewable substrates such as glucose or glycerol. Our modular pathway framework achieves carbon-chain extension by two different mechanisms. A fatty acid synthesis route is used to generate longer chains heptane and nonane, while a more energy efficient alternative, reverse-beta-oxidation, is used for synthesis of propane, butane, and pentane. We demonstrate that both upstream (thiolase) and intermediate (thioesterase) reactions can act as control points for chain-length specificity. Specific free fatty acids are subsequently converted to alkanes using a broad-specificity carboxylic acid reductase and a cyanobacterial aldehyde decarbonylase (AD). The selectivity obtained by different module pairings provides a foundation for tuning alkane product distribution for desired fuel properties. Alternate ADs that have greater activity on shorter substrates improve observed alkane titer. However, even in an engineered host strain that significantly reduces endogenous conversion of aldehyde intermediates to alcohol byproducts, AD activity is observed to be limiting for all chain lengths. Given these insights, we discuss guiding principles for pathway selection and potential opportunities for pathway improvement. PMID- 26556132 TI - Synthesis and cation distribution in the new bismuth oxyhalides with the Sillen Aurivillius intergrowth structures. AB - About 20 new compounds with the Sillen-Aurivillius intergrowth structure, Me(1)Me(2)Bi3Nb2O11X (Me(1) = Pb, Sr, Ba; Me(2) = Ca, Sr, Ba; X = Cl, Br, I), have been prepared. They are composed of stacking of [ANb2O7] perovskite blocks, fluorite-type [M2O2] blocks and halogen sheets. The cation distribution between the fluorite and perovskite layers has been studied for Ba2Bi3Nb2O11I, Ca1.25Sr0.75Bi3Nb2O11Cl, BaCaBi3Nb2O11Br and Sr2Bi3Nb2O11Cl. The smaller Me cations tend to reside in the perovskite block while the larger ones are situated in the fluorite-type block. The distribution of the elements was confirmed for BaCaBi3Nb2O11Br using energy dispersive X-ray analysis combined with scanning transmission electron microscopy (STEM-EDX). An electron diffraction study of this compound reveals a local symmetry lowering caused by weakly correlated rotation of NbO6 octahedra. Based on our findings, we suggest a new stability criterion for mixed-layer structures, which is that net charges of any two consecutive layers do not compensate for each other and only the whole layer sequence is electroneutral. PMID- 26556133 TI - Comparison of various semen extenders and addition of prostaglandin F2alpha on pregnancy rate in cows. AB - This investigation comprises three trials. Trial 1 consists of an in vitro comparison of three semen extenders: two egg yolk based (customized Tris-egg yolk glycerol and Triladyl(r)), the third (AndroMed(r)) soybean lecithin based. With regard to post-thaw motility, the phytoextender AndroMed(r) proved to be superior (59+/-3% v. 53+/-2% and 53+/-2%, P<0.05). It had earlier been shown that addition of the commercial prostaglandin F2alpha preparation Dinolytic(r) before freezing compromises post-thaw motility; therefore, in Trial 2, Dinolytic(r) was added after thawing. Frozen-thawed spermatozoa tolerated addition of Dinolytic(r) at a concentration of 30% (v/v). In Trial 3, cows were inseminated using straws in which diluted semen and Dinolytic(r) were frozen in the same straw, separated by an air bubble, so intermingling could only take place in the course of insemination. Pregnancy rates at Dinolytic(r) dosages of 0%, 30% or 60% amounted to 44%, 41% and 56%, respectively (P>0.05), a result that encourages a large scale field study, which is envisioned. PMID- 26556134 TI - Neural Devices: New Ethics? PMID- 26556135 TI - CAHPS Surveys: Valid and Valuable Measures of Patient Experience. PMID- 26556136 TI - The Authors Reply. PMID- 26556137 TI - Courage, Context, and Contemporary Health Care. PMID- 26556138 TI - A Clinical Ethicist's Thank-You. PMID- 26556139 TI - Fever. PMID- 26556140 TI - A Buyer's Market? Fixing the Price for Human Ova for Assisted Reproduction. PMID- 26556141 TI - A Vaping Matter: E-cigarette Use in Health Care Organizations. PMID- 26556142 TI - "Lethal" Fetal Anomalies and Elective Cesarean. PMID- 26556143 TI - Bioethics Casebook 2.0: Using Web-Based Design and Tools to Promote Ethical Reflection and Practice in Health Care. PMID- 26556144 TI - Engineering the Brain: Ethical Issues and the Introduction of Neural Devices. AB - Neural devices now under development stand to interact with and alter the human brain in ways that may challenge standard notions of identity, normality, authority, responsibility, privacy and justice. PMID- 26556145 TI - Neural Technologies: The Ethics of Intimate Access to the Mind. PMID- 26556149 TI - Waving Goodbye to Waivers of Consent. PMID- 26556150 TI - Looking up: Views from our fellows' retreat. PMID- 26556151 TI - Application of encapsulation technology in stem cell therapy. AB - Stem cells are characterized by their capacity for self-renewal and their ability to differentiate into specific cell types under the influence of their microenvironment. These cells are potent therapeutic tools to treat various regenerative diseases based on their ability to produce a therapeutic protein or restore natural tissue function with minimal side effects. However, a major problem that must be overcome is to find a suitable stem cell delivery system. Cell encapsulation is a novel concept in which cells are immobilized inside a biocompatible and semi-permeable natural or synthetic matrix. The purpose of encapsulation is to protect the cell from the host's immune system, improve cell expansion and maintain cell viability, self-renewal potency and direct cell differentiation toward a desired lineage. This review will provide an overview of the application of encapsulation technology for phenotypic and functional improvement of stem cells and using these encapsulated cells to treat various diseases. PMID- 26556152 TI - Research "push", long term-change, and general practice. AB - PURPOSE: Intervention evaluations have not always accounted for long-term implementation of interventions. The purpose of this paper is to explore implementation of a primary care intervention during the lifespan of the trial and beyond. DESIGN/METHODOLOGY/APPROACH: Eight general practices participated in the trial (four control and four intervention). In-depth interviews (with nine GPs and four practices nurses who delivered the intervention) and observation methods were employed. Thematic analysis was utilized and Normalization Process Theory (NPT) constructs were compared with emergent themes. FINDINGS: Macro-level policy imperatives shaped practice priorities which resulted in the "whole system" new intervention not being perceived to be sustainable. Continued routinization of the intervention into usual care beyond the lifespan of the funded study was dependent on individualized monitoring and taking forward tacit knowledge. RESEARCH LIMITATIONS/IMPLICATIONS: The authors discuss the implications of these findings for sociological theories of implementation and understanding outcomes of research led complex interventions. ORIGINALITY/VALUE: The study describes the complex interplay between macro processes and individual situated practices and contributes to understanding if, how, and why interventions are sustained beyond initial "research push". The value of the study lies in describing the conditions and potential consequences of long-term implementation, which might be translated to other contexts. PMID- 26556153 TI - The contribution of community leadership upon the performance of mutual health organisations in Ghana. AB - PURPOSE: The purpose of this paper is to investigate the effect of social dynamics on the performance of mutual health organisations (MHOs) exploring the influence of community wealth and community leadership on policy implementation. DESIGN/METHODOLOGY/APPROACH: Four operating district mutual health insurance schemes were selected using geographical locations, among other criteria, as case studies. Data were gathered through interviews and documentary review. The findings were analysed using community field and social capital theories. FINDINGS: Traditional leaders like the Chiefs serve as the pivot around which social and human capital of the communities revolve in the developmental process of the country. RESEARCH LIMITATIONS/IMPLICATIONS: Lack of exhaustive examination of the financial and institutional viability issues of the MHOs. Future studies could assess the interplay between financial, institutional and social viability models when measuring the financial and overall sustainability of MHOs. PRACTICAL IMPLICATIONS: Health policy makers need to involve traditional leaders in the formulation and implementation of national policies since their acceptance or rejection of central government policy could have negative consequences. SOCIAL IMPLICATIONS: Ghana is a dynamic country and there is the need to utilise existing social networks: inter-family and inter-tribal relationships to ensure the viability of MHOs. ORIGINALITY/VALUE: There is and can be a successful interplay between public sector funding and community sector revenue mobilisation for financing the health sector in Ghana. This justifies the complementarity between government funding and community's resource mobilisation efforts in the health sector. PMID- 26556154 TI - Participation in medical college activities: a case study of the Australasian experience. AB - PURPOSE: Medical Colleges rely on the volunteer labour of their Fellows to undertake their key functions. In the Australasian context, there is anecdotal evidence to suggest that Fellow participation is declining. The purpose of this paper is to examine the main factors that influence Fellows' participation in the activities of a Medical College. DESIGN/METHODOLOGY/APPROACH: The authors conducted three focus groups with Fellows who exhibit varying levels of participation with the Medical College in 2012. FINDINGS: The research identified individual and organisational factors which influence the propensity of Fellows to volunteer their time to the Medical College. At an individual level, Fellows cite a number of factors which motivate them to volunteer their time to the Medical College, including: altruistic reasons; giving back to the profession and community; and the benefits that Fellow's receive from their participation in College activities, including enhancing their status within the profession. However, Fellows also report issues of work-family integration, balancing Medical College and work-related responsibilities as factors precluding them from participating in Medical College activities. Fellows also noted several factors related to the operation of the Medical College which inhibited their participation in the Medical College, including the perceived exclusivity of the Medical College, a lack of service orientation towards Fellows, a lack of recognition of the work of Fellows and a perceived lack of advocacy on the part of the Medical College. ORIGINALITY/VALUE: This paper highlights that the participation of Fellows in their Medical Colleges is essential to maintaining quality standards and the effective operation of Australasian healthcare. These preliminary results indicate that there are several factors which discourage Fellow participation in Medical College activities, suggesting a need for Medical Colleges to develop strategies to address these issues. PMID- 26556155 TI - Reorganising hospitals to implement a patient-centered model of care: Effects on clinical practice and professional relationships in the Italian NHS. AB - PURPOSE: The purpose of this paper is to understand how the introduction of a patient-centered model (PCM) in Italian hospitals affects the pre-existent configuration of clinical work and interacts with established intra/inter professional relationships. DESIGN/METHODOLOGY/APPROACH: Qualitative multi-phase study based on three main sources: health policy analysis, an exploratory interview study with senior managers of eight Italian hospitals implementing the PCM, and an in-depth case study that involved managerial and clinical staff of one Italian hospital implementing the PCM. FINDINGS: The introduction of the PCM challenges clinical work and professional relationships, but such challenges are interpreted differently by the organisational actors involved, thus giving rise to two different "narratives of change". The "political narrative" (the views conveyed by formal policies and senior managers) focuses on the power shifts and conflict between nurses and doctors, while the "workplace narrative" (the experiences of frontline clinicians) emphasises the problems linked to the disruption of previous discipline-based inter-professional groups. PRACTICAL IMPLICATIONS: Medical disciplines, rather than professional groupings, are the main source of identification of doctors and nurses, and represent a crucial aspect of clinicians' professional identity. Although the need for collaboration among medical disciplines is acknowledged, creating multi-disciplinary groups in practice requires the sustaining of new aggregators and binding forces. ORIGINALITY/VALUE: This study suggests further acknowledgment of the inherent complexity of the political and workplace narratives of change rather than interpreting them as the signal of irreconcilable perspectives between managers and clinicians. By addressing the specific issues regarding which the political and workplace narratives clash, relationship of trust may be developed through which problems can be identified, mutually acknowledged, articulated, and solved. PMID- 26556156 TI - Culture and cognition in health systems change. AB - PURPOSE: Large-scale change involves modifying not only the structures and functions of multiple organizations, but also the mindsets and behaviours of diverse stakeholders. This paper focuses on the latter: the informal, less visible, and often neglected psychological and social factors implicated in change efforts. The purpose of this paper is to differentiate between the concepts of organizational culture and mental models, to argue for the value of applying a shared mental models (SMM) framework to large-scale change, and to suggest directions for future research. DESIGN/METHODOLOGY/APPROACH: The authors provide an overview of SMM theory and use it to explore the dynamic relationship between culture and cognition. The contributions and limitations of the theory to change efforts are also discussed. FINDINGS: Culture and cognition are complementary perspectives, providing insight into two different levels of the change process. SMM theory draws attention to important questions that add value to existing perspectives on large-scale change. The authors outline these questions for future research and argue that research and practice in this domain may be best served by focusing less on the potentially narrow goal of "achieving consensus" and more on identifying, understanding, and managing cognitive convergences and divergences as part of broader research and change management programmes. ORIGINALITY/VALUE: Drawing from both cultural and cognitive paradigms can provide researchers with a more complete picture of the processes by which coordinated action are achieved in complex change initiatives in the healthcare domain. PMID- 26556157 TI - The impact of mindfulness on leadership effectiveness in a health care setting: a pilot study. AB - PURPOSE: The purpose of this paper is to examine the impact of mindfulness awareness practice (MAP) on mid-level health-care managers' leadership. DESIGN/METHODOLOGY/APPROACH: In total, 11 mid-level health-care managers in eastern Canada took part in an intensive weekend retreat and a follow-up webinar on mindfulness awareness. Perceived stress and leadership effectiveness were assessed pre- and post-intervention (i.e. four and eight weeks). A control group (n=10) also completed the same measures twice. Additionally, informants (n=28) provided assessments of participants' leadership pre- and post-intervention. Follow-up interviews were carried out with eight participants 12-16 weeks post intervention. FINDINGS: In comparison to controls, retreat participants showed significant increases in mindfulness and corresponding decreases in stress that were sustained across eight weeks post-retreat; retreat participants reported significant positive changes in their leadership effectiveness that were corroborated by informants. Qualitative data, however, suggest that sustaining a mindfulness practice presents significant challenges to middle managers in a health care setting. RESEARCH LIMITATIONS/IMPLICATIONS: The findings are useful to management working in health services that are plagued by increasing demands and changes. Despite the small sample and lack of random assignment, the pilot data support the efficacy of MAP in improving leadership. ORIGINALITY/VALUE: Little empirical research supports the claim that MAP enhances leadership. The present study employed a mixed methods approach to address this gap and demonstrates the potential benefits of MAP among mid-level managers. PMID- 26556158 TI - Examining challenges to reliability of health service accreditation during a period of healthcare reform in Australia. AB - PURPOSE: Health systems are changing at variable rates. Periods of significant change can create new challenges or amplify existing barriers to accreditation program credibility and reliability. The purpose of this paper is to examine, during the transition to a new Australian accreditation scheme and standards, challenges to health service accreditation survey reliability, the salience of the issues and strategies to manage threats to survey reliability. DESIGN/METHODOLOGY/APPROACH: Across 2013-2014, a two-phase, multi-method study was conducted, involving five research activities (two questionnaire surveys and three group discussions). This paper reports data from the transcribed group discussions involving 100 participants, which was subject to content and thematic analysis. Participants were accreditation survey coordinators employed by the Australian Council on Healthcare Standards. FINDINGS: Six significant issues influencing survey reliability were reported: accreditation program governance and philosophy; accrediting agency management of the accreditation process, including the program's framework; survey coordinators; survey team dynamics; individual surveyors; and healthcare organizations' approach to accreditation. A change in governance arrangements promoted reliability with an independent authority and a new set of standards, endorsed by Federal and State governments. However, potential reliability threats were introduced by having multiple accrediting agencies approved to survey against the new national standards. Challenges that existed prior to the reformed system remain. ORIGINALITY/VALUE: Capturing lessons and challenges from healthcare reforms is necessary if improvements are to be realized. The study provides practical and theoretical strategies to promote reliability in accreditation programs. PMID- 26556159 TI - Lessons from Albion: Can Australia learn from England's approach to primary healthcare funding? AB - PURPOSE: As Australia struggles to meet increased demand for healthcare and contain expenditure there has been a focus on primary care and its role in demand management and keeping people out of expensive secondary care. However, with domestic policy struggling to find a suitable approach consideration of English policy could well be fruitful in the quest to strengthen and develop primary care in Australia. The purpose of this paper is to consider policy developments in England and explores these in relation to the Australian healthcare system. DESIGN/METHODOLOGY/APPROACH: The authors highlight the key changes to policy that have occurred in the English healthcare system in recent years, and discuss whether they have proven successful. The authors discuss the barriers to implementing similar approaches in Australia, particularly the difference in system structure that would necessitate policy adaptation. FINDINGS: Whilst there are differences in the structure and organisation of funding and service provision between countries, there are developments in England that are worthy of consideration from an Australian perspective. These include a focus on funding and commissioning that rewards quality not just activity and volume. As Australia sees the development of new primary care organisations that are tasked with commissioning then developments and lessons around the technical and relational aspects will be important to consider. ORIGINALITY/VALUE: The work highlights that Australia might consider learning from the English experience in this area and the types of incentives that may increase efficiency and quality of health service provision. This is important as it potentially gives greater certainty about those approaches most likely to yield beneficial outcomes for patients and the broader system. PMID- 26556160 TI - How hospitalists work to pull healthcare teams together. AB - PURPOSE: The purpose of this paper is to document everyday practices by which hospitalist physicians negotiate barriers to effective teamwork. DESIGN/METHODOLOGY/APPROACH: Ethnographic observation with a sample of hospitalists chosen to represent a range of hospital and practice types. FINDINGS: Hospitals rely on effective, interprofessional teamwork but typically do not support it. Hospitalist physicians must bridge the internal boundaries within their hospitals to coordinate their patients' care, but they face challenges - scattered patients, fragmented information, uncoordinated teams, and unreliable processes - that can impact the timeliness and safety of care. Hospitalists largely rely on personal presence and memory to deal with these challenges. Some invent low-tech supports for teamwork, but these are typically neither tested nor shared with others. Formal support for teamwork, primarily case management rounds, is applied unevenly and may not be respected by all team members. RESEARCH LIMITATIONS/IMPLICATIONS: The findings are drawn from observation over a limited period of time with a small, purposefully chosen sample of physicians and hospitals. Practical implications - Hospitals must recognize the issues hospitalists and other providers face, evaluate and disseminate supports for teamwork, and make interprofessional teamwork a core feature of hospital design and evaluation. ORIGINALITY/VALUE: The authors show the nuances of how hospitalists struggle to practice teamwork in a challenging context, and how the approaches they take (relying on memory and personal presence) do not address, and may actually contribute to, the system-level problems they face. PMID- 26556161 TI - Providing rehabilitation online - invisible work and diagnostic agents. AB - PURPOSE: Telecare promises to deliver healthcare services more efficiently while, at the same time, improving the quality of care. The purpose of this paper is to challenge these promises by analysing the implications of introducing telecare in the rehabilitation of patients suffering from chronic obstructive pulmonary disease. DESIGN/METHODOLOGY/APPROACH: Empirically, the paper is based on interviews with and observations of rehabilitation therapists and patients taking part in a Danish telerehabilitation programme. Theoretically, the paper draws on Science and Technology Studies. FINDINGS: The introduction of telecare alters rehabilitation practices in multiple ways. First, several new time-consuming work routines, carried out in collaboration between therapists, patients and technical professions, emerge. Although crucial in establishing and maintaining telerehabilitation infrastructures, this work remains invisible in evaluations of the programme. Second, rather than simply increasing patient agency, responsibilities are redistributed and negotiated in subtle and non-uniform ways. These negotiations make it less transparent where one responsibility begins and where another potentially conflicting one ends. PRACTICAL IMPLICATIONS: Evaluations of telecare technologies should pay more attention to work- and responsibility-related effects of introducing telecare in order better to account for predicted and unpredicted as well as desirable and undesirable socio technical changes. ORIGINALITY/VALUE: Using an ethnographic approach, the paper points to the discrepancy between simplistic political promises that telecare technologies can serve as tools for improvement, on the one hand, and the substantial changes in the organisation and management of healthcare observed in practice, on the other. Rather than regarding telecare as technologies of improvement, it is more productive to regard them as technologies of change. PMID- 26556162 TI - Hospital management training for the Eastern Mediterranean Region: time for a change? AB - PURPOSE: The WHO Eastern Mediterranean Regional Office has emphasized health system strengthening among the top five strategic priorities. One of the integral elements of health systems are the hospitals. The purpose of this paper is to review the need for formalized training in hospital management to improve the quality of care. DESIGN/METHODOLOGY/APPROACH: Literature review and hands on experience of conducting a regional training in hospital management for Eastern Mediterranean Region (EMR) countries. FINDINGS: Majority of patients in EMR bypass Primary Health Care facilities due to inadequate quality of services and prefer seeking specialized care at a tertiary level. There is mounting evidence of mediocre to poor patient satisfaction due to inefficient health care practices in hospitals of EMR. Strengthening the management capacity of the hospitals through a formal training programme is therefore necessary for improving the performance of health care delivery and the overall health system. Hospital management encompasses hospital planning and operational activities including development and implementation of organizational strategies to ensure adequate numbers and quality of trained human resources and effective financial management, disaster management, health management information system utilization, support services, biomedical engineering, transport and waste management. Such training will prepare health care professionals with leadership skills to deliver quality hospital services. ORIGINALITY/VALUE: This is one of the first papers emphasizing the need for a formal structured regional training in hospital management for the countries of EMR. A modular incremental training approach developing an EMR Credit Transfer and Accumulation system is proposed. PMID- 26556163 TI - Evaluating Schwartz Center Rounds in an urban hospital center. AB - PURPOSE: Schwartz Center Rounds (SCRs) bring multidisciplinary caregivers together to discuss authentic patient cases from the social and emotional perspective. The monthly sessions provide a forum to share personal thoughts and feelings. The purpose of this paper is to learn why people attend SCR, understand what is gained from the experience, and identify key elements to use in measuring the program's effectiveness. DESIGN/METHODOLOGY/APPROACH: This qualitative descriptive study used four focus groups and three telephone interviews for data collection. Purposive sampling resulted in a multidisciplinary sample of 30 participants. Thematic analysis was conducted with complete transcripts by all researchers. FINDINGS: All parties viewed SCR as beneficial. Six themes emerged during data analysis: culture change, exposing emotions, walking in another's shoes, inequality of topics, influence of rules and boundaries, and personal impact. Institutional culture was positively influenced through SCR. RESEARCH LIMITATIONS/IMPLICATIONS: Limitations include a single institution and restricted data gathered from physicians. Future research should focus on identifying outcome measures to evaluate the long-term impact of SCR on healthcare organizations. PRACTICAL IMPLICATIONS: This study confirms that the SCR program should be continued at the study organization, and expanded to increase availability to all staff. The growth of this program in healthcare organizations across the country is encouraged. ORIGINALITY/VALUE: This research provides support for healthcare organizations to offer SCR and highlights how the emotional aspects of patient care can be acknowledged, explored, and discussed. PMID- 26556164 TI - Strategies to promote practice nurse capacity to deliver evidence-based care: An example from sexual healthcare. AB - PURPOSE: Evidence-based practice is pivotal to effective patient care. However, its translation into practice remains limited. Given the central role of primary care in many healthcare systems, it is important to identify strategies that bolster clinician-capacity to promote evidence-based care. The purpose of this paper is to identify strategies to increase Practice Nurse capacity to promote evidence-based sexual healthcare within general practice. DESIGN/METHODOLOGY/APPROACH: A survey of 217 Practice Nurses in an Australian state and ten respondent-interviews regarding two resources to promote evidence based sexual healthcare - namely, a clinical aide and online training. FINDINGS: The perceived impact of both resources was determined by views on relevance and design - particularly for the clinical aide. Resource-use was influenced by role and responsibilities within the workplace, accessibility, and support from patients and colleagues. RESEARCH LIMITATIONS/IMPLICATIONS: This is the first Australian study to reveal strategies to promote evidence-based sexual healthcare among Practice Nurses. The findings provide a platform for future research on knowledge translation processes, particularly among clinicians who might be disengaged from sexual healthcare. PRACTICAL IMPLICATIONS: Given the benefits of evidence-based practices, it is important that managers recognize their role, and the role of their services, in promoting these. Without explicit support for evidence-based care and recognition of the Practice Nurse role in such care, knowledge translation is likely to be limited. ORIGINALITY/VALUE: Knowledge translation among Practice Nurses can be facilitated by: resources-deemed informative, relevant, and user-friendly, as well as support from patients, colleagues, and their workplace. PMID- 26556165 TI - Responses to professional identity threat: Identity management strategies in incident narratives of health care professionals. AB - PURPOSE: The purpose of this paper is to explore sensemaking of incidents by health care professionals through an analysis of the role of professional identity in narratives of incidents. Using insights from social identity theory, the authors argue that incidents may create a threat of professional identity, and that professionals make use of identity management strategies in response to this identity threat. DESIGN/METHODOLOGY/APPROACH: The paper draws on a qualitative analysis of incident narratives in 14 semi-structured interviews with physicians, nurses, and residents at a Dutch specialist hospital. The authors used an existing framework of identity management strategies to categorize the narratives. FINDINGS: The analysis yielded two main results. First, nurses and residents employed multiple types of identity management strategies simultaneously, which points to the possible benefit of combining different strategies. Second, physicians used the strategy of patronization of other professional groups, a specific form of downward comparison. RESEARCH LIMITATIONS/IMPLICATIONS: The authors discuss the implications of the findings in terms of the impact of identity management strategies on the perpetuation of hierarchical differences in health care. PRACTICAL IMPLICATIONS: The authors argue that efforts to manage incident handling may profit from considering social identity processes in sensemaking of incidents. ORIGINALITY/VALUE: This is the first study that systematically explores how health care professionals use identity management strategies to maintain a positive professional identity in the face of incidents. This study contributes to research on interdisciplinary cooperation in health care. PMID- 26556166 TI - Managing processes of inpatient care and treatment: Swedish healthcare process managers' descriptions. AB - PURPOSE: The purpose of this paper is to establish a knowledge bank for the development of overall hospital processes. Description and analysis are used to show how process managers experience their situation and the various possibilities it offers for active management in the context of managing processes of inpatient care and treatment at Swedish hospitals. DESIGN/METHODOLOGY/APPROACH: A qualitative and explorative design with open-ended interviews with 12 process managers at three Swedish hospitals was used. Transcribed interviews were analysed by means of latent content analysis. FINDINGS: The two main categories emerging from the analysis were characteristics of process leadership and prerequisites of process management. Quality, relational and knowledge dimensions, and structure, time and information dimensions emerged as their respective sub-categories. The overall theme describes the interdependence between leadership characteristics and the prerequisites necessary for effective process management. RESEARCH LIMITATIONS/IMPLICATIONS: No generalizations could be made from the results of the qualitative interview studies but a deeper understanding of the phenomenon was reached, which in turn can be transferred to similar settings. ORIGINALITY/VALUE: This study contributes qualitative descriptions of leadership characteristics and the prerequisites necessary for active process management in the context of managing processes of inpatient care and treatment at Swedish hospitals, a subject that has not been investigated earlier. PMID- 26556167 TI - The importance of role sending in the sensemaking of change agent roles. AB - PURPOSE: The purpose of this paper is to investigate what happens when a lack of role-sending results in ambiguous change agent roles during a large scale organisational reconfiguration. The authors consider the role of sensemaking in resolving role ambiguity of middle manager change agents and the consequences of this for organisational restructuring. DESIGN/METHODOLOGY/APPROACH: Data were collected from a case study analysis of significant organisational reconfiguration across a local National Health Service Trust in the UK. Data consists of 82 interviews, complemented by analysis of over 100 documents and field notes from 51 hours of observations collected over five phases covering a three year period before, during and after the reconfiguration. An inductive qualitative analysis revealed the sensemaking processes by which ambiguity in role definition was resolved. FINDINGS: The data explains how change agents collectively make sense of a role in their own way, drawing on their own experiences and views as well as cues from other organisational members. The authors also identified the organisational outcomes which resulted from this freedom in sensemaking. This study demonstrates that by leaving too much flexibility in the definition of the role, agents developed their own sensemaking which was subsequently very difficult to manipulate. PRACTICAL IMPLICATIONS: In creating new roles, management first needs to have a realistic vision of the task and roles that their agents will perform, and second, to communicate these expectations to both those responsible for recruiting these roles and to the agents themselves. ORIGINALITY/VALUE: Much of the focus in sensemaking research has been on the importance of change agents' sensemaking of the change but there has been little focus on how change agents sensemake their own role in the change. PMID- 26556168 TI - Is psychotropic medication use related to organisational and treatment culture in residential care. AB - PURPOSE: The purpose of this paper is to establish the relationship between organisational culture and psychotropic medication use in residential care. DESIGN/METHODOLOGY/APPROACH: Cross-sectional analyses of staff and resident's record survey in residential aged care facilities in Auckland, New Zealand (NZ). The competing values framework categorised organisational culture as clan, hierarchical, market driven or adhocracy and was completed by all staff. The treatment culture tool categorised facilities as having resident centred or traditional culture and was completed by registered nursing staff and general practitioners (GP). Functional and behavioural characteristics of residents were established by staff report and health characteristics and medications used were ascertained from the health record. Multiple regression was used to test for associations between measures of culture with psychotropic medication use (anxiolytics, sedatives, major tranquillisers). FINDINGS: In total 199 staff, 27 GP and 527 residents participated from 14 facilities. On average 8.5 medications per resident were prescribed and 42 per cent of residents received psychotropic medication. Having a diagnosis of anxiety or depression (odds ratio (OR) 3.18, 95 per cent confidence interval (CI) 1.71, 5.91), followed by persistent wandering (OR 2.53, 95 per cent CI 1.59, 4.01) and being in a dementia unit (OR 2.45, 95 per cent CI 1.17, 5.12) were most strongly associated with psychotropic use. Controlling for resident- and facility-level factors, health care assistants' assignation of hierarchical organisational culture type was independently associated with psychotropic medication use, (OR 1.29, CI 1.08, 1.53) and a higher treatment culture score from the GP was associated with lower use of psychotropic medication (OR 0.95, CI 0.92, 0.98). ORIGINALITY/VALUE: Psychotropic medication use remains prevalent in residential care facilities in NZ. Interventions aimed at changing organisational culture towards a less hierarchical and more resident-centred culture may be another avenue to improve prescribing in residential aged care. PMID- 26556169 TI - Managing different forms of distances in Dutch healthcare organizations: The relation between managers and professionals as a dynamic continuum of distance and proximity. AB - PURPOSE: Dichotomous "gap" thinking about professionals and managers has important limits. The purpose of this paper is to study the specific ontology of "the gap" in which different forms of distances are defined. DESIGN/METHODOLOGY/APPROACH: In order to deepen the knowledge of the actual day to-day tasks of Dutch healthcare executives an ethnographic study of the daily work of Dutch healthcare executives and an ontological exploration of the concept "gap" was provided. The study empirically investigates the meaning given to the concept of "distance" in healthcare governance practices. FINDINGS: The study reveals that healthcare executives have to fulfil a dual role of maintaining distance and creating proximity. Coping with different forms of distances seems to be an integral part of their work. They make use of four potential mechanisms to cope with distance in their healthcare organization practices. ORIGINALITY/VALUE: The relationship between managers and professionals is often defined as a dichotomous gap. The findings in this research suggest a more dynamic picture of the relationship between managers and professionals than is currently present in literature. This study moves "beyond" the gap and investigates processes of distancing in-depth. PMID- 26556170 TI - New nurse transition: success through aligning multiple identities. AB - PURPOSE: The purpose of this paper is to explore the perceptions of new nurses in Singapore of their experiences of role transition and to examine the implications for managers in terms of employee training, development and retention. DESIGN/METHODOLOGY/APPROACH: This qualitative study was conducted using a constructivist grounded theory approach. In total 26 novice nurses and five preceptors (n=31) from five different hospitals participated in the study. Data were collected from semi-structured interviews and reflective journal entries and analysed using the constant comparative method. FINDINGS: The findings revealed that novice nurses remained emotionally and physically challenged when experiencing role transition. Two major constructs appear to play an important part in the transition process; learning how to Fit in and aligning personal with professional and organisational identities. The findings highlight factors that facilitate or impede Fitting in and aligning these identities. ORIGINALITY/VALUE: Although the concept of Fitting in and its relation to the attrition of novice nurses has been explored in global studies, that relationship has not yet been theorised as the dynamic alignment of multiple identities. Also, whilst most research around Fitting in, identity and retention has been conducted in western countries, little is known about these issues and their interrelationship in the context of Singapore. The study should inform decision making by healthcare organisations, nurse managers and nursing training institutions with respect to improving the transition experience of novice nurses. PMID- 26556171 TI - Configurations of leadership practices in hospital units. AB - PURPOSE: The purpose of this paper is to explore how leadership is practiced across four different hospital units. DESIGN/METHODOLOGY/APPROACH: The study is a comparative case study of four hospital units, based on detailed observations of the everyday work practices, interactions and interviews with ten interdisciplinary clinical managers. FINDINGS: Comparing leadership as configurations of practices across four different clinical settings, the author shows how flexible and often shared leadership practices were embedded in and central to the core clinical work in all units studied here, especially in more unpredictable work settings. Practices of symbolic work and emotional support to staff were particularly important when patients were severely ill. RESEARCH LIMITATIONS/IMPLICATIONS: Based on a study conducted with qualitative methods, these results cannot be expected to apply in all clinical settings. Future research is invited to extend the findings presented here by exploring leadership practices from a micro-level perspective in additional health care contexts: particularly the embedded and emergent nature of such practices. PRACTICAL IMPLICATIONS: This paper shows leadership practices to be primarily embedded in the clinical work and often shared across organizational or professional boundaries. ORIGINALITY/VALUE: This paper demonstrated how leadership practices are embedded in the everyday work in hospital units. Moreover, the analysis shows how configurations of leadership practices varied in four different clinical settings, thus contributing with contextual accounts of leadership as practice, and suggested "configurations of practice" as a way to carve out similarities and differences in leadership practices across settings. PMID- 26556172 TI - Investigating healthcare IT innovations: a "conceptual blending" approach. AB - PURPOSE: The purpose of this paper is to better understand how and why adoption and implementation of healthcare IT innovations occur. The authors examine two IT applications, computerised physician order entry (CPOE) and picture archiving and communication systems (PACS) at the meso and micro levels, within the context of the National Programme for IT in the English National Health Service (NHS). DESIGN/METHODOLOGY/APPROACH: To analyse these multi-level dynamics, the authors blend Rogers' diffusion of innovations theory (DoIT) with Webster's sociological critique of technological innovation in medicine and healthcare systems to illuminate a wider range of interacting factors. Qualitative data collected between 2004 and 2006 uses semi-structured, in-depth interviews with 72 stakeholders across four English NHS hospital trusts. FINDINGS: Overall, PACS was more successfully implemented (fully or partially in three out of four trusts) than CPOE (implemented in one trust only). Factors such as perceived benefit to users and attributes of the application - in particular speed, ease of use, reliability and flexibility and levels of readiness - were highly relevant but their influence was modulated through interaction with complex structural and relational issues. PRACTICAL IMPLICATIONS: Results reveal that combining contextual system level theories with DoIT increases understanding of real-life processes underpinning implementation of IT innovations within healthcare. They also highlight important drivers affecting success of implementation, including socio-political factors, the social body of practice and degree of "co construction" between designers and end-users. ORIGINALITY/VALUE: The originality of the study partly rests on its methodological innovativeness and its value on critical insights afforded into understanding complex IT implementation programmes. PMID- 26556173 TI - A suite of de novo c-type cytochromes for functional oxidoreductase engineering. AB - Central to the design of an efficient de novo enzyme is a robust yet mutable protein scaffold. The maquette approach to protein design offers precisely this, employing simple four-alpha-helix bundle scaffolds devoid of evolutionary complexity and with proven tolerance towards iterative protein engineering. We recently described the design of C2, a de novo designed c-type cytochrome maquette that undergoes post-translational modification in E. coli to covalently graft heme onto the protein backbone in vivo. This de novo cytochrome is capable of reversible oxygen binding, an obligate step in the catalytic cycle of many oxygen-activating oxidoreductases. Here we demonstrate the flexibility of both the maquette platform and the post-translational machinery of E. coli by creating a suite of functional de novo designed c-type cytochromes. We explore the engineering tolerances of the maquette by selecting alternative binding sites for heme C attachment and creating di-heme maquettes either by appending an additional heme C binding motif to the maquette scaffold or by binding heme B through simple bis-histidine ligation to a second binding site. The new designs retain the essential properties of the parent design but with significant improvements in structural stability. Molecular dynamics simulations aid the rationalization of these functional improvements while providing insight into the rules for engineering heme C binding sites in future iterations. This versatile, functional suite of de novo c-type cytochromes shows significant promise in providing robust platforms for the future engineering of de novo oxygen activating oxidoreductases. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electron transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID- 26556174 TI - Comment on New Mathematical Model for Interpreting pH-Stat Digestion Profiles: Impact of Lipid Droplet Characteristics on in Vitro Digestibility. PMID- 26556175 TI - Leading Causes of Death Contributing to Decrease in Life Expectancy Gap Between Black and White Populations: United States, 1999-2013. AB - Life expectancy at birth has increased steadily since 1900 to a record 78.8 years in 2013. But differences in life expectancy between the white and black populations still exist, despite a decrease in the life expectancy gap from 5.9 years in 1999 to 3.6 years in 2013. Differences in the change over time in the leading causes of death for the black and white populations have contributed to this decrease in the gap in life expectancy. Between 1999 and 2013, the decrease in the life expectancy gap between the black and white populations was mostly due to greater decreases in mortality from heart disease, cancer, HIV disease, unintentional injuries, and perinatal conditions among the black population. Similarly, the decrease in the gap between black and white male life expectancy was due to greater decreases in death rates for HIV disease, cancer, unintentional injuries, heart disease, and perinatal conditions in black males. For black females, greater decreases in diabetes death rates, combined with decreased rates for heart disease and HIV disease, were the major causes contributing to the decrease in the life expectancy gap with white females. The decrease in the gap in life expectancy between the white and black populations would have been larger than 3.6 years if not for increases in death rates for the black population for aortic aneurysm, Alzheimer's disease, and maternal conditions. For black males, the causes that showed increases in death rates over white males were hypertension, aortic aneurysm, diabetes, Alzheimer's disease, and kidney disease, while the causes that showed increases in death rates for black females were Alzheimer's disease, maternal conditions, and atherosclerosis. This NCHS Data Brief is the second in a series of data briefs that explore the causes of death contributing to differences in life expectancy between detailed ethnic and racial populations in the United States. The first data brief focused on the racial differences in life expectancy for a single year, 2010 (3). PMID- 26556176 TI - Systematic and differential myelination of axon collaterals in the mammalian auditory brainstem. AB - A brainstem circuit for encoding the spatial location of sounds involves neurons in the cochlear nucleus that project to medial superior olivary (MSO) neurons on both sides of the brain via a single bifurcating axon. Neurons in MSO act as coincidence detectors, responding optimally when signals from the two ears arrive within a few microseconds. To achieve this, transmission of signals along the contralateral collateral must be faster than transmission of the same signals along the ipsilateral collateral. We demonstrate that this is achieved by differential regulation of myelination and axon caliber along the ipsilateral and contralateral branches of single axons; ipsilateral axon branches have shorter internode lengths and smaller caliber than contralateral branches. The myelination difference is established prior to the onset of hearing. We conclude that this differential myelination and axon caliber requires local interactions between axon collaterals and surrounding oligodendrocytes on the two sides of the brainstem. PMID- 26556177 TI - Diagnostic accuracy for apical and chronic periodontitis biomarkers in gingival crevicular fluid: an exploratory study. AB - AIM: The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and asymptomatic apical periodontitis ( AAP). MATERIALS AND METHODS: Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained (N = 106). Matrix metalloproteinases (MMPs) -2 and -9 were determined by zymography; levels of MMP 8 by ELISA and IFMA and MPO by ELISA. IL-1, IL-6, TNFalpha, DKK-1, Osteonectin, Periostin, TRAP-5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed-effects models. RESULTS: The MMP-9 and MMP-8 were higher in CP, followed by AAP, versus healthy individuals (p < 0.05). ProMMP-2, MPO, IL-1, IL-6, PTN, TRAP-5 and OPG were significantly higher in CP when compared with AAP and healthy patients (p < 0.05). The highest diagnostic accuracies were observed for ProMMP-2, ProMMP-9, MMP-8 and TRAP-5 (AUC > 0.97) in CP, and for the active form of MMP-9 and MMP-8 (AUC > 0.90) in AAP. CONCLUSION: Gingival crevicular fluid composition is modified by CP and AAP. MMP-9 and MMP-8 show diagnostic potential for CP and AAP, whereas MMP-2 and TRAP-5 are useful only for CP. PMID- 26556178 TI - Compatibility between livestock databases used for quantitative biosecurity response in New Zealand. AB - AIM: To characterise New Zealand's livestock biosecurity databases, and investigate their compatibility and capacity to provide a single integrated data source for quantitative outbreak analysis. METHODS: Contemporary snapshots of the data in three national livestock biosecurity databases, AgriBase, FarmsOnLine (FOL) and the National Animal Identification and Tracing Scheme (NAIT), were obtained on 16 September, 1 September and 30 April 2014, respectively, and loaded into a relational database. A frequency table of animal numbers per farm was calculated for the AgriBase and FOL datasets. A two dimensional kernel density estimate was calculated for farms reporting the presence of cattle, pigs, deer, and small ruminants in each database and the ratio of farm densities for AgriBase versus FOL calculated. The extent to which records in the three databases could be matched and linked was quantified, and the level of agreement amongst them for the presence of different species on properties assessed using Cohen's kappa statistic. RESULTS: AgriBase contained fewer records than FOL, but recorded animal numbers present on each farm, whereas FOL contained more records, but captured only presence/absence of animals. The ratio of farm densities in AgriBase relative to FOL for pigs and deer was reasonably homogeneous across New Zealand, with AgriBase having a farm density approximately 80% of FOL. For cattle and small ruminants, there was considerable heterogeneity, with AgriBase showing a density of cattle farms in the Central Otago region that was 20% of FOL, and a density of small ruminant farms in the central West Coast area that was twice that of FOL. Only 37% of records in FOL could be linked to AgriBase, but the level of agreement for the presence of different species between these databases was substantial (kappa>0.6). Both NAIT and FOL shared common farm identifiers which could be used to georeference animal movements, and there was a fair to substantial agreement (kappa 0.32-0.69) between these databases for the presence of cattle and deer on properties. CONCLUSIONS: The three databases broadly agreed with each other, but important differences existed in both species composition and spatial coverage which raises concern over their accuracy. Importantly, they cannot be reliably linked together to provide a single picture of New Zealand's livestock industry, limiting the ability to use advanced quantitative techniques to provide effective decision support during disease outbreaks. We recommend that a single integrated database be developed, with alignment of resources and legislation for its upkeep. PMID- 26556179 TI - Conformational analysis of small organic molecules using NOE and RDC data: A discussion of strychnine and alpha-methylene-gamma-butyrolactone. AB - To understand the properties and/or reactivity of an organic molecule, an understanding of its three-dimensional structure is necessary. Simultaneous determination of configuration and conformation often poses a daunting challenge. Thus, the more information accessible for a given molecule, the better. Additionally to (3)J-couplings, two sources of information, quantitative NOE and more recently also RDCs, are used for conformational analysis by NMR spectroscopy. In this paper, we compare these sources of conformational information in two molecules: the configurationally well-characterized strychnine 1, and the only recently configurationally and conformationally characterized alpha-methylene-gamma-butyrolactone 2. We discuss possible sources of error in the measurement and analysis process, and how to exclude them. By this means, we are able to bolster the previously proposed flexibility for these two molecules. PMID- 26556180 TI - Effects of Aging and Cardiovascular Disease Risk Factors on the Expression of Sirtuins in the Human Corpus Cavernosum. AB - INTRODUCTION: Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. AIM: The aim of this study was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC relatively to age and CVDRF. METHODS: Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1-3 and SIRT5-7 mRNAs was assessed by real time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. MAIN OUTCOME MEASURES: The main outcome measure was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC. RESULTS: SIRT1-3 and SIRT5-7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser(1177) levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). CONCLUSIONS: Our results demonstrate for the first time expression of SIRT2-3 and SIRT5-7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury. PMID- 26556181 TI - Diffusion tensor imaging in abdominal organs. AB - Initially, diffusion tensor imaging (DTI) was mainly applied in studies of the human brain to analyse white matter tracts. As DTI is outstanding for the analysis of tissue's microstructure, the interest in DTI for the assessment of abdominal tissues has increased continuously in recent years. Tissue characteristics of abdominal organs differ substantially from those of the human brain. Further peculiarities such as respiratory motion and heterogenic tissue composition lead to difficult conditions that have to be overcome in DTI measurements. Thus MR measurement parameters have to be adapted for DTI in abdominal organs. This review article provides information on the technical background of DTI with a focus on abdominal imaging, as well as an overview of clinical studies and application of DTI in different abdominal regions. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26556182 TI - A new microplatform based on titanium dioxide nanofibers/graphene oxide nanosheets nanocomposite modified screen printed carbon electrode for electrochemical determination of adenine in the presence of guanine. AB - The current techniques for determining adenine have several shortcomings such as high cost, high time consumption, tedious pretreatment steps and the requirements for highly skilled personnel often restrict their use in routine analytical practice. This paper describes the development and utilization of a new nanocomposite consisting of titanium dioxide nanofibers (TNFs) and graphene oxide nanosheets (GONs) for screen printed carbon electrode (SPCE) modification. The synthesized GONs and TNFs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The modified electrode (TNFs/GONs/SPCE) was used for electrochemical characterization of adenine. The TNFs/GONs/SPCE exhibited an increase in peak current and the electron transfer kinetics and decrease in the overpotential for the oxidation reaction of adenine. Using differential pulse voltammetry (DPV), the prepared sensor showed good sensitivity for determining adenine in two ranges from 0.1-1 and 1-10 MUM, with a detection limit (DL) of 1.71 nM. Electrochemical studies suggested that the TNFs/GONs/SPCE provided a synergistic augmentation on the voltammetric behavior of electrochemical oxidation of adenine, which was indicated by the improvement of anodic peak current and a decrease in anodic peak potential. The amount of adenine in pBudCE4.1 plasmid was determined via the proposed sensor and the result was in good compatibility with the sequence data of pBudCE4.1 plasmid. PMID- 26556183 TI - Synergetic catalysis based on the proline tailed metalloporphyrin with graphene sheet as efficient mimetic enzyme for ultrasensitive electrochemical detection of dopamine. AB - In this paper, linking with the butoxycarbonyl (BOC) protection of proline, a new tailed metalloporphyrin with many useful active functions, nickel (II) 5-[4-N (tert-Butoxycarbonyl)-l-prolinecoxylpropyloxy]phenyl-10,15,20-triphenylporphyrin (NiTBLPyP), was designed and synthesized. And the NiTBLPyP polymer (poly(NiTBLPyP)) was successfully obtained via a low-cost electrochemical method and exploited as an efficient mimic enzyme. Subsequently, a noncovalent nanohybrid of poly(NiTBLPyP) with graphene (rGO) sheet (rGO-poly(NiTBLPyP)) was prepared through pi-pi stacking interaction for the ultrasensitive and selective detection of DA. The nanohybrid was characterized by UV-vis spectroscopy, Fourier transform infrared spectra, Raman spectroscopy, scanning electron microscopy and electrochemical impedance spectroscopy. Due to the excellent electrocatalytic ability of poly(NiTBLPyP) film and aromatic pi-pi stacking interaction between poly(NiTBLPyP and rGO sheet, the obtained rGO-poly(NiTBLPyP) film exhibited a great synergistic amplification effect toward dopamine oxidation. Under optimum experimental conditions, the logarithm of catalytic currents showed a good linear relationship with that of the dopamine concentration in the range of 0.01-200 MUM with a low detection limit of 1.40 nM. With good sensitivity and selectivity, the present method was applied to the determination of DA in real sample and the results was satisfactory. Thus, the rGO-poly(NiTBLPyP) film is one of the promising mimetic enzyme for electrocatalysis and relevant fields. PMID- 26556184 TI - A simple microfluidic aggregation analyzer for the specific, sensitive and multiplexed quantification of proteins in a serum environment. AB - Portable and low-cost platforms for protein biomarker detection are highly sought after for point of care applications. We demonstrate a simple microfluidic device for the rapid, electrically-based detection of proteins in serum. Our aggregation analyzer relies on detecting the protein-induced aggregation of sub-micron particles, using a one-step procedure followed by a fast, particle-by-particle measurement with a very high count rate. This enables the rapid and precise quantification of C-Reactive protein levels, within the clinically relevant range, using unprocessed human serum and a disposable microfluidic device; no optics are involved in the implementation. Due to the single particle detection format and the use of microfluidics, only a small volume of serum (~50 nL) is needed to complete the analysis. The method can be easily extended to multiplexed biomarker detection by combining an assay using differently sized particles, each targeting a separate protein. We illustrate this by using two sizes of latex beads and demonstrating the simultaneous detection of two different proteins in a serum environment with minimal cross-interference. This confirms that our aggregation analyzer platform provides a simple and straightforward method for multiplexed biomarker detection in a low cost, portable design. PMID- 26556185 TI - A double signal electrochemical human immunoglobulin G immunosensor based on gold nanoparticles-polydopamine functionalized reduced graphene oxide as a sensor platform and AgNPs/carbon nanocomposite as signal probe and catalytic substrate. AB - In this paper, a double signal electrochemical Human immunoglobulin G (HIgG) immunosensor based on AgNPs/carbon nanocomposite (Ag/C NC) as the signal probe and catalytic substrate was developed for fast and sensitive detection of HIgG. The as-prepared AuNPs-PDA-rGO nanocomposite and Ag/C NC were confirmed by UV-vis, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. Electrochemical impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry were used to investigate the electrochemical properties of the proposed immunosensor. The AuNPs-PDA-rGO nanocomposite can improve the electron transfer rate and capture more Ab1. In the sandwich-type immunoassay process, the Ag/C NC functionalized bioconjugates were captured on HIgG/Ab1/AuNPs-PDA-rGO surface and the electrochemical double-signal strategy was employed. These double electrochemical detection signals were directly monitored the oxidation current originated from Ag/C NC and indirectly detected the reduction current of benzoquinone which was produced from the reaction of H2O2 and HQ by catalysis of Ag/C NC in electrochemical detection of HIgG. Under the optimized conditions, the current responses were changed with the concentrations of HIgG for the proposed immunosensor with wide linear ranges of 0.1 to 100 ngmL(-1) and 0.01-100 ngmL(-1) with the lowest detection concentration of 0.001 ng mL(-1) in the absence and presence of H2O2 and HQ. The double-signal strategy is used for detection of HIgG, and the results came from the two signals were well consistent with each other. The proposed immunosensor was successfully applied in analysis of human IgG in real samples and this strategy may provide a relative simple and effective method for construction of other immunsensors in detection of other biomarkers in clinical medicine. PMID- 26556186 TI - Spin-coated Au-nanohole arrays engineered by nanosphere lithography for a Staphylococcus aureus 16S rRNA electrochemical sensor. AB - The nanopatterning of gold nanoparticle (AuNP) arrays on an indium tin oxide (ITO) electrode using efficient and low-cost methods is described. This process used nanosphere lithography (NSL) encompassing the deposition of monolayered Polystyrene (PS) followed by a convective self-assembly drop coating protocol onto the ITO substrate that further acted as the mask after the AuNP assembly. The results showed that spin-coating allowed AuNPs to follow the contour and adhere to the PS nanospheres. The final products, after etching the PS, generated a highly ordered Au-nanohole array on an ITO substrate. The Au-nanohole arrays on the ITO electrode provided a greater surface area and successfully enhanced the peak current of electrochemical measurements by 82% compared with bare ITO and was used to detect Staphylococcus aureus 16S rRNA hybridization. In contrast to non-templated AuNP structures, the Au-nanohole arrays on the ITO electrode contributed to an optimum sensitivity improvement in DNA hybridization detection by 23%, along with an impressive limit of detection (LOD) of 10 pM. The high specificity of this distinguished structure was also achieved in the hybridization measurements of multi-analyte pathogens. These findings indicate that the combination of PS nanosphere lithography, followed by the spin-coating of AuNPs, leads to an inexpensive and simple engineering process that effectively generates uniform Au-nanohole arrays on ITO, which provides a greater surface area to optimize the electrochemical performance of the DNA biosensor. PMID- 26556187 TI - Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection. AB - Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process. PMID- 26556189 TI - Recently Investigated Natural Gums and Mucilages as Pharmaceutical Excipients: An Overview. AB - Due to advances in drug delivery technology, currently, excipients are included in novel dosage forms to fulfil specific functions and in some cases they directly or indirectly influence the extent and/or rate of drug release and drug absorption. Recent trends towards use of plant based and natural products demand the replacement of synthetic additives with natural ones. Today, the whole world is increasingly interested in natural drugs and excipients. These natural materials have many advantages over synthetic ones as they are chemically inert, nontoxic, less expensive, biodegradable, and widely available. This review discusses majority of the plant-derived polymeric compounds (gums and mucilage's), their sources, chemical constituents, uses, and some recent investigations as excipients in novel drug delivery systems. PMID- 26556188 TI - A Critical Appraisal of Solubility Enhancement Techniques of Polyphenols. AB - Polyphenols constitute a family of natural substances distributed widely in plant kingdom. These are produced as secondary metabolites by plants and so far 8000 representatives of this family have been identified. Recently, there is an increased interest in the polyphenols because of the evidence of their role in prevention of degenerative diseases such as neurodegenerative diseases, cancer, and cardiovascular diseases. Although a large number of drugs are available in the market for treatment of these diseases, however, the emphasis these days is on the exploitation of natural principles derived from plants. Most polyphenols show low in vivo bioavailability thus limiting their application for oral drug delivery. This low bioavailability could be associated with low aqueous solubility, first pass effect, metabolism in GIT, or irreversible binding to cellular DNA and proteins. Therefore, there is a need to devise strategies to improve oral bioavailability of polyphenols. Various approaches like nanosizing, self-microemulsifying drug delivery systems (SMEDDS), microencapsulation, complexation, and solid dispersion can be used to increase the bioavailability. This paper will highlight the various methods that have been employed till date for the solubility enhancement of various polyphenols so that a suitable drug delivery system can be formulated. PMID- 26556190 TI - Solubility Enhancement of Budesonide and Statistical Optimization of Coating Variables for Targeted Drug Delivery. AB - The purpose of the research was to present Budesonide (BUD) as a novel formulation showing improved aqueous solubility, which may decrease variability in C max? and T max? found in inflammatory bowel disease (IBD) patients, and drug targeting to colon. To improve aqueous solubility, solid dispersion (SD) of the BUD with poloxamer 188 was prepared by melting method. Physical characterization of solid dispersion was performed. The SD was used to prepare tablet equivalent to 9 mg of BUD. The tablet was coated with enteric polymers Eudragit S100 and Eudragit L100 to target colon. The ratio of polymers and percentage coating was optimized using statistical design. Variables studied in design were ratio of enteric polymers and the effect of percentage coating on in vitro drug release. Dissolution at different pH showed that drug release in colon could be modified by optimizing the ratio of polymers and percentage coating. The dissolution data showed that the percentage coating and ratio of polymers are very important to get lag time and optimum formulation. The optimized batch from statistical design was kept under accelerated condition for three months. After accelerated stability study, there was no significant change in the drug release. PMID- 26556191 TI - Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals. AB - Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals. PMID- 26556192 TI - Development and Evaluation of Novel Self-Nanoemulsifying Drug Delivery Systems Based on a Homolipid from Capra hircus and Its Admixtures with Melon Oil for the Delivery of Indomethacin. AB - In this study, goat fat (Capra hircus) and melon oil were extracted and used to formulate self-nanoemulsifying drug delivery systems (SNEDDS) based on either goat fat alone or its admixture with melon oil by employing escalating ratios of oil(s), surfactant blend (1 : 1 Tween 60 and Tween 80), and cosurfactant (Span 85), with or without carbosil, a glidant, for the delivery of indomethacin. The formulations were encapsulated in hard gelatin capsules and then assessed using isotropicity test, aqueous dilution stability and precipitation propensity, absolute drug content, emulsification time, in vitro drug release, and anti inflammatory activity. The SNEDDS exhibited low precipitation propensity and excellent stability on copious dilution, as well as high drug release in vitro and in vivo. The inhibition produced by the SNEDDS was comparable to that of indomethacin injection (positive control) for much of the 5 h test period, indicating a high degree of bioavailability of the administered SNEDDS. The absolute drug contents and emulsification times fell within narrow limits. This study has shown that a 1 : 1 ratio of melon oil and goat fat could confer favourable properties with respect to drug release and anti-inflammatory activity on SNEDDS for the delivery of indomethacin, thus encouraging further development of the formulations. PMID- 26556194 TI - Emerging Trends in Noninvasive Insulin Delivery. AB - This paper deals with various aspects of oral insulin delivery system. Insulin is used for the treatment of diabetes mellitus, which is characterized by the elevated glucose level (above the normal range) in the blood stream, that is, hyperglycemia. Oral route of administration of any drug is the most convenient route. Development of oral insulin is still under research. Oral insulin will cause the avoidance of pain during the injection (in subcutaneous administration), anxiety due to needle, and infections which can be developed. Different types of enzyme inhibitors, like sodium cholate, camostat, mesilate, bacitracin, leupeptin, and so forth, have been used to prevent insulin from enzymatic degradation. Subcutaneous route has been used for administration of insulin, but pain and itching at the site of administration can occur. That is why various alternative routes of insulin administration like oral route are under investigation. In this paper authors summarized advancement in insulin delivery with their formulation aspects. PMID- 26556195 TI - Serratiopeptidase Niosomal Gel with Potential in Topical Delivery. AB - The objective of present study was to develop nonionic surfactant vesicles of proteolytic enzyme serratiopeptidase (SRP) by adapting reverse phase evaporation (REV) technique and to evaluate the viability of SRP niosomal gel in treating the topical inflammation. The feasibility of SRP niosomes by REV method using Span 40 and cholesterol has been successfully demonstrated in this investigation. The entrapment efficiency was found to be influenced by the molar ratio of Span 40 : cholesterol and concentration of SRP in noisome. The developed niosomes were characterized for morphology, particle size, and in vitro release. Niosomal gel was prepared by dispersing xanthan gum into optimized batch of SRP niosomes. Ex vivo permeation and in vivo anti-inflammatory efficacy of gel formulation were evaluated topically. SRP niosomes obtained were round in nanosize range. At Span 40 : cholesterol molar ratio 1 : 1 entrapment efficiency was maximum, that is, 54.82% +/- 2.08, and showed consistent release pattern. Furthermore ex vivo skin permeation revealed that there was fourfold increase in a steady state flux when SRP was formulated in niosomes and a significant increase in the permeation of SRP, from SRP niosomal gel containing permeation enhancer. In vivo efficacy studies indicated that SRP niosomal gel had a comparable topical anti inflammatory activity to that of dicolfenac gel. PMID- 26556193 TI - Microbicides for the Treatment of Sexually Transmitted HIV Infections. AB - Approximately 34 million people were living with human immunodeficiency virus (HIV-1) at the end of 2011. From the last two decades, researchers are actively involved in the development of an effective HIV-1 treatment, but the results intended are still doubtful about the eradication of HIV. The HIV-1 virus has gone from being an "inherently untreatable" infectious agent to the one liable to be affected by a range of approved therapies. Candidate microbicides have been developed to target specific steps in the process of viral transmission. Microbicides are self-administered agents that can be applied to vaginal or rectal mucosal surfaces with the aim of preventing, or reducing, the transmission of sexually transmitted infections (STIs) including HIV-1. The development of efficient, widely available, and low-cost microbicides to prevent sexually transmitted HIV infections should be given high priority. In this review, we studied the various forms of microbicides, their mechanism of action, and their abundant approaches to control the transmission of sexually transmitted infections (STIs). PMID- 26556196 TI - Design and Evaluation of Voriconazole Eye Drops for the Treatment of Fungal Keratitis. AB - Voriconazole is a novel antifungal agent with excellent broad spectrum activity commercially available for oral and intravenous administration. The purpose of this study was to prepare ophthalmic formulation of hydroxypropyl beta cyclodextrin (HP-beta-CD) based voriconazole containing benzalkonium chloride BAK and EDTA with or without viscosity modifiers and study its permeation characteristics through freshly excised goat cornea. The results were observed that viscosity and force of bioadhesion of the voriconazole HP-beta-CD solutions containing xanthan gum (XG) are more as compared to polyvinyl alcohol. The results revealed that voriconazole drop containing PVA provided least viscosity and higher corneal permeation of drug, while drop formulated with XG had maximum viscosity and least permeation. The HP-beta-CD based voriconazole (1.5%) ophthalmic formulation containing xanthan gum (1.5), preserved with BAK and EDTA, could provide shelf life of 2 years. The microbiological studies showed that voriconazole ophthalmic solution containing xanthan gum shows better antifungal activity as compared to voriconazole and xanthan gum alone. Thus, it can be concluded that HP-beta-CD based voriconazole (1.5%, pH 7.0) ophthalmic solution containing BAK and EDTA with viscosity modifier XG provided maximum precorneal residence time as compared to other viscosity modifiers and polyvinyl alcohol provided less precorneal residence time than other viscosity modifiers. PMID- 26556197 TI - Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy. AB - The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism. PMID- 26556198 TI - Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization. AB - The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results. PMID- 26556199 TI - The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients. AB - Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V 2/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V 3/F), and absorption rate (k a ) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h(-1), respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy. PMID- 26556200 TI - Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique. AB - Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol) were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation. PMID- 26556201 TI - Development of Budesonide Loaded Biopolymer Based Dry Powder Inhaler: Optimization, In Vitro Deposition, and Cytotoxicity Study. AB - The progress in the development of DPI technology has boosted the use of sensitive drug molecules for lung diseases. However, delivery of these molecules from conventional DPI to the active site still poses a challenge with respect to deposition efficiency in the lung. At same time, serious systemic side effects of drugs have become a cause for concern. The developed budesonide loaded biopolymer based controlled release DPI had shown maximum in vitro lung deposition with least toxicity. The subject of present study, lactose-free budesonide loaded biopolymer based DPI, further corroborates the great potential of antiasthmatic drugs. This technology is expected to revolutionize the approaches towards enhanced therapeutic delivery of prospective drugs. PMID- 26556202 TI - Lipid-Based Drug Delivery Systems. AB - The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. The use of lipids in drug delivery is no more a new trend now but is still the promising concept. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address challenges like the solubility and bioavailability of poorly water-soluble drugs. Lipid-based formulations can be tailored to meet a wide range of product requirements dictated by disease indication, route of administration, cost consideration, product stability, toxicity, and efficacy. These formulations are also a commercially viable strategy to formulate pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. In addition, lipid-based formulations have been shown to reduce the toxicity of various drugs by changing the biodistribution of the drug away from sensitive organs. However, the number of applications for lipid-based formulations has expanded as the nature and type of active drugs under investigation have become more varied. This paper mainly focuses on novel lipid-based formulations, namely, emulsions, vesicular systems, and lipid particulate systems and their subcategories as well as on their prominent applications in pharmaceutical drug delivery. PMID- 26556203 TI - Formulation Development and Evaluation of Fast Disintegrating Tablet of Cetirizine Hydrochloride: A Novel Drug Delivery for Pediatrics and Geriatrics. AB - Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of Cetirizine Hydrochloride for allergic and respiratory disorders. As precision of dosing and patient's compliance become important prerequisite for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient's acceptability. Hence, the present investigation was undertaken with a view to develop a fast disintegrating tablet of Cetirizine Hydrochloride which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as Sodium Starch Glycolate were optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug excipient compatibility and accelerated stability study. It was concluded that fast disintegrating tablets of Cetirizine Hydrochloride were formulated successfully with desired characteristics which disintegrated rapidly, provide rapid onset of action, and enhance the patient convenience and compliance. PMID- 26556204 TI - Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride. AB - In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms. PMID- 26556205 TI - Development and Validation of Liquid Chromatographic Method for Estimation of Naringin in Nanoformulation. AB - A simple, precise, accurate, rapid, and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method with UV detection has been developed and validated for quantification of naringin (NAR) in novel pharmaceutical formulation. NAR is a polyphenolic flavonoid present in most of the citrus plants having variety of pharmacological activities. Method optimization was carried out by considering the various parameters such as effect of pH and column. The analyte was separated by employing a C18 (250.0 * 4.6 mm, 5 MUm) column at ambient temperature in isocratic conditions using phosphate buffer pH 3.5: acetonitrile (75 : 25% v/v) as mobile phase pumped at a flow rate of 1.0 mL/min. UV detection was carried out at 282 nm. The developed method was validated according to ICH guidelines Q2(R1). The method was found to be precise and accurate on statistical evaluation with a linearity range of 0.1 to 20.0 MUg/mL for NAR. The intra- and interday precision studies showed good reproducibility with coefficients of variation (CV) less than 1.0%. The mean recovery of NAR was found to be 99.33 +/- 0.16%. The proposed method was found to be highly accurate, sensitive, and robust. The proposed liquid chromatographic method was successfully employed for the routine analysis of said compound in developed novel nanopharmaceuticals. The presence of excipients did not show any interference on the determination of NAR, indicating method specificity. PMID- 26556206 TI - Preparation and In Vitro Evaluation of Ethylcellulose and Polymethacrylate Resins Loaded Microparticles Containing Hydrophilic Drug. AB - Objective. The purpose of the recent study was to prepare and estimate sustained release of Ethylcellulose (300 cps) and Eudragit (RS 100 and RL 100) microparticles containing Propranolol hydrochloride used as a treatment of cardiovascular system, especially hypertension. Method. Propranolol hydrochloride was microencapsulated with different polymers (Ethylcellulose, Eudragit RS, and Eudragit RL) using modified hydrophobic (O/O) solvent evaporation method using 1 : 1 combination of acetone and isopropanol as the internal phase. Obtained microparticles were showing higher batch yield with higher encapsulation efficiency. Microparticles were prepared with different ratios of 1 : 1, 1 : 3, 1 : 5, and 1 : 7 (%, wt/wt) using span 80 (%, v/v) as a surfactant. Results. The influence of formulation factors like drug: polymer ratio, internal phase, and type of polymers on obtained microparticles was characterized with respect to particle size distribution, encapsulation efficiency, percentage yield, FTIR, and FE-SEM. Higher encapsulation efficiencies were obtained with various polymers like Ethylcellulose (96.63 +/- 0.5) compared to Eudragit RS 100 (83.70 +/- 0.6) and RL 100 (89.62 +/- 0.6). The in vitro release study was characterized by initial burst. Conclusion. The result of study displays that Ethylcellulose and Eudragit loaded microparticles of Propranolol hydrochloride can be effectively prepared using modified hydrophobic emulsification solvent evaporation technique. Therefore, the modified hydrophobic emulsion technique can also be applied to the preparation of microparticles for low molecular weight and highly water soluble drugs. PMID- 26556207 TI - FDA-Approved Natural Polymers for Fast Dissolving Tablets. AB - Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID- 26556208 TI - Temporal stability and responsiveness of the Montreal Cognitive Assessment following acquired brain injury. AB - OBJECTIVES: To evaluate the temporal stability and responsiveness of the Montreal Cognitive Assessment (MoCA) in acquired brain injury (ABI). RESEARCH DESIGN AND METHODS: English-speaking adults with stroke or moderate-to-severe traumatic brain injury were administered alternate forms of the MoCA (version 1, then 2), 6 weeks apart. Chronic group participants (n = 40) were community-dwelling, at least 1 year post-ABI (mean = 12.1 years, SD = 9.0), and presumed clinically stable. Sub-acute group participants (n = 36) were 30.8 days post-ABI (SD = 12.4) and were undergoing intensive rehabilitation. Individuals with an unstable medical or psychiatric condition or severe receptive aphasia were not eligible. RESULTS: The chronic group scored 21.6 (SD = 4.5) initially and 22.7 (SD = 3.8) on the second administration, demonstrating a small but significant practise effect (p = 0.009). The Pearson test-re-test correlation coefficient was 0.83. Using reliable change methodology in the chronic group, the 80% confidence interval (CI) for change across the two administrations was -2 to +4, adjusting for practise. Applied to the sub-acute group, 39% improved and 0% declined. CONCLUSIONS: The MoCA is a brief standardized tool that appears useful for monitoring cognitive change after ABI. The findings enable clinicians to detect statistically reliable change across serial MoCA administrations in individuals with an ABI. PMID- 26556209 TI - Home management of acute medical complications in cancer patients: a prospective pilot study. AB - BACKGROUND: The development of reliable alternatives to conventional hospitalization in patients with cancer would have great clinical and economical value. The aim of the present study was to assess the feasibility of a home-based nursing intervention model as a safe alternative for the management of acute medical complications in cancer patients who would otherwise require conventional hospitalization. PATIENTS AND METHODS: From October 2013 to October 2014, we prospectively evaluated the outcomes of consecutive acute medical episodes treated at home under the home-based intervention program named the Bridge Project (BP). Episodes were classified as "avoided hospitalization in outpatients" (AHO) vs. "reduced hospitalization in inpatients" (RHI). The primary end-point was to assess the rate and causes of BP intervention failure (unplanned hospital readmission or death). RESULTS: Two hundred and forty-six consecutive episodes (52 % AHO and 48 % RHI) involving 203 patients (55 % male; mean age 63 years) were enrolled. The main conditions managed at home were non-neutropenic infections (40 %), febrile neutropenia (20 %), and cancer-related complications (28 %). The median duration of the BP intervention was 5 days (range 1-16 days). No deaths were reported at home. Unplanned hospital readmissions occurred in 9 % of episodes (14 % in AHO vs. 4 % in RHI; p = 0.001). Five of the 22 readmitted patients (22.7 % of the BP failures; 2.5 % of the whole series) died during hospitalization. The BP intervention burden was 1353 days, representing a potential saving of 14 % of days of hospitalization during the study period. CONCLUSIONS: The BP is a safe intervention which can potentially avoid or reduce the length of hospitalization in selected cancer patients with acute medical complications. Our findings support further development of innovative home-based clinical approaches to promote potentially avoidable hospitalization in this setting. PMID- 26556210 TI - Aromatase inhibitor induced musculoskeletal syndrome: a significant problem with limited treatment options. AB - BACKGROUND: Aromatase inhibitor induced musculoskeletal syndrome is experienced by approximately half of women taking aromatase inhibitors, impairing quality of life and leading some to discontinue treatment. Evidence for effective treatments is lacking. We aimed to understand the manifestations and impact of this syndrome in the Australian breast cancer community, and strategies used for its management. METHODS: A survey invitation was sent to 2390 members of the Breast Cancer Network Australia Review and Survey Group in April 2014. The online questionnaire included 45 questions covering demographics, aromatase inhibitor use, clinical manifestations and risk factors for the aromatase inhibitor musculoskeletal syndrome, reasons for treatment discontinuation and efficacy of interventions used. RESULTS: Aromatase inhibitor induced musculoskeletal syndrome was reported by 302 (82 %) of 370 respondents. Twenty-seven percent had discontinued treatment for any reason and of these, 68 % discontinued because of the musculoskeletal syndrome. Eighty-one percent had used at least one intervention from the following three categories to manage the syndrome: doctor prescribed medications, over-the-counter/complementary medicines or alternative/non-drug therapies. Anti-inflammatories, paracetamol (acetaminophen) and yoga were most successful in relieving symptoms in each of the respective categories. Almost a third of respondents reported that one or more interventions helped prevent aromatase inhibitor discontinuation. However, approximately 20 % of respondents found no intervention effective in any category. CONCLUSION: We conclude that aromatase inhibitor induced musculoskeletal syndrome is a significant issue for Australian women and is an important reason for treatment discontinuation. Women use a variety of interventions to manage this syndrome; however, their efficacy appears limited. PMID- 26556213 TI - Construction, Enzyme Response, and Substrate Capacity of a Hyaluronan Cyclodextrin Supramolecular Assembly. AB - A supramolecular assembly was constructed with a cationic cyclodextrin (EICD) and native hyaluronan (HA). The cationic carboxylic ester pendants on HA support hyaluronidase (HAase)-responsive sites and the EICD supports artificial carboxylic esterase responsive sites. Substrate-binding models were investigated by using environment-sensitive fluorescence probes 2-p-toluidino-6 naphthalenesulfoniate sodium (2,6-TNS) and thioflavin T (ThT). On a HA/EICD assembly, EICD was able to bind an anionic substrate and HA and EICD constructed the cationic substrate binding site together. This assembly could be used as a sequential dual-substrate carrier. PMID- 26556212 TI - Mother-caregiver expectations for function among survivors of childhood brain tumors. AB - PURPOSE: Children diagnosed with brain tumors increasingly survive to adulthood, although they do so with needs often requiring continued parental caregiving. We sought to describe the nature of caregivers' expectations about survivors' function and how expectations connect to ongoing management and decision-making. METHODS: Forty-five qualitative interviews with mother-caregivers were conducted and coded for themes related to expectations for their adolescent/young adult children living post-childhood brain tumors. RESULTS: Five main themes emerged as integral to mother-caregiver expectations: realizing a difference in the survivor, noticing limitations to independence in the survivor, memories of learning about clinical prognoses as understood from consent meetings and education, managing these realizations, and acknowledging unresolved challenges. CONCLUSIONS: Caregiver expectations are influenced by both initial clinical interactions and contemporary family dynamics and require individual- and family specific survivorship planning. As caregiver expectations can influence management behaviors that impact outcomes and possibly independence, implications for clinician-caregiver shared decision-making are substantial. PMID- 26556211 TI - Non-pharmacological cancer pain interventions in populations with social disparities: a systematic review and meta-analysis. AB - INTRODUCTION: Global advances in pain relief have improved the quality of life of cancer populations. Yet, variation in cancer pain outcomes has been found in populations with social disparities compared to mainstream groups. Populations with social disparities bear an inequitable distribution of resources such as ethnic minorities, low income individuals, and women in vulnerable circumstances. RESEARCH PURPOSE: A systematic review and meta-analysis of the effect of non pharmacological cancer pain interventions in cancer populations with social disparities of income, ethnicity, or gender. METHODS: Randomized controlled trials, controlled trials, and before and after studies were targeted through comprehensive multidatabase searches. Two reviewers independently screened titles/abstracts for potentially relevant studies and reviewed the full text of relevant articles for inclusion. Data were extracted from included studies by one reviewer and verified by another reviewer. Four reviewers independently completed quality assessment. Studies were grouped by intervention. Effects were evaluated for heterogeneity and pooled. RESULTS: The search found 5219 potential records. Full text of 26 reports was evaluated. Three randomized controlled trials (RCTs) met inclusion criteria, targeting ethnic minorities and underserved populations and/or women. Interventions included education, coaching, and online support groups. Studies found no significant differences in pain reduction between intervention and control groups or between ethnic minorities and their counterparts. A high risk of bias was found in all studies. Meta-analysis found no statistically significant difference on pain intensity among underserved groups, ethnic minorities, or between ethnic minorities and white counterparts. CONCLUSION: Results show the need to examine supportive care interventions particularly in populations with social disparities. PMID- 26556214 TI - Mitochondrial DNA Fragmentation to Monitor Processing Parameters in High Acid, Plant-Derived Foods. AB - Mitochondrial DNA (mtDNA) fragmentation was assessed in acidified foods. Using quantitative polymerase chain reaction, Ct values measured from fresh, fermented, pasteurized, and stored cucumber mtDNA were determined to be significantly different (P > 0.05) based on processing and shelf-life. This indicated that the combination of lower temperature thermal processes (hot-fill at 75 degrees C for 15 min) and acidified conditions (pH = 3.8) was sufficient to cause mtDNA fragmentation. In studies modeling high acid juices, pasteurization (96 degrees C, 0 to 24 min) of tomato serum produced Ct values which had high correlation to time-temperature treatment. Primers producing longer amplicons (approximately 1 kb) targeting the same mitochondrial gene gave greater sensitivity in correlating time-temperature treatments to Ct values. Lab-scale pasteurization studies using Ct values derived from the longer amplicon differentiated between heat treatments of tomato serum (95 degrees C for <2 min). MtDNA fragmentation was shown to be a potential new tool to characterize low temperature (<100 degrees C) high acid processes (pH < 4.6), nonthermal processes such as vegetable fermentation and holding times of acidified, plant-derived products. PMID- 26556215 TI - Why the war on drugs in sport will never be won. AB - Recent exposes of drug use in sports suggest that doping might be more problematic than doping-control test results reveal. A zero-tolerance (ZT) model, which aims to eliminate the use, has dominated the thinking of sport's policy makers over the last 15 years. In light of the limitations associated with ZT based policy, we propose an alternative policy, one based on controlled use and harm reduction principles. We argue that substance control policies underpinned by harm reduction (HR) principles of social utility and public value will deliver superior social outcomes. First, a harm reduction approach better accommodates the competitive realities of sports and the impact of elite sports' emphasis on performance at all costs. Second, HR prioritises athlete welfare over sport and brand reputation. Finally, while appreciating the regulatory and risk management responsibilities of sports' governing bodies, the HR model offers greater space to the athlete's right to privacy, and right to personal autonomy. PMID- 26556216 TI - The Interservice Physician Assistant Program: The veterans' solution. PMID- 26556217 TI - Primary care assessment of patients at risk for suicide. AB - Primary care providers (PCPs) play a crucial role caring for patients with depression, managing antidepressant therapy, and assessing patients for suicide risk. Ten percent of the more than 20 million primary care visits for depression each year involve mental health issues, and account for 62% of the antidepressants prescribed in the United States. Psychiatric disorders appear to be underrecognized and undertreated in primary care. Suicidal ideation is present in a significant percentage of depressed primary care patients but rarely discussed. This article describes the warning signs and risk factors associated with suicide and recommends screening tools that can help PCPs identify patients at risk. PMID- 26556218 TI - Chemical Shifts to Metabolic Pathways: Identifying Metabolic Pathways Directly from a Single 2D NMR Spectrum. AB - Identifying cellular processes in terms of metabolic pathways is one of the avowed goals of metabolomics studies. Currently, this is done after relevant metabolites are identified to allow their mapping onto specific pathways. This task is daunting due to the complex nature of cellular processes and the difficulty in establishing the identity of individual metabolites. We propose here a new method: ChemSMP (Chemical Shifts to Metabolic Pathways), which facilitates rapid analysis by identifying the active metabolic pathways directly from chemical shifts obtained from a single two-dimensional (2D) [(13)C-(1)H] correlation NMR spectrum without the need for identification and assignment of individual metabolites. ChemSMP uses a novel indexing and scoring system comprised of a "uniqueness score" and a "coverage score". Our method is demonstrated on metabolic pathways data from the Small Molecule Pathway Database (SMPDB) and chemical shifts from the Human Metabolome Database (HMDB). Benchmarks show that ChemSMP has a positive prediction rate of >90% in the presence of decluttered data and can sustain the same at 60-70% even in the presence of noise, such as deletions of peaks and chemical shift deviations. The method tested on NMR data acquired for a mixture of 20 amino acids shows a success rate of 93% in correct recovery of pathways. When used on data obtained from the cell lysate of an unexplored oncogenic cell line, it revealed active metabolic pathways responsible for regulating energy homeostasis of cancer cells. Our unique tool is thus expected to significantly enhance analysis of NMR-based metabolomics data by reducing existing impediments. PMID- 26556219 TI - Association of NR3C1/Glucocorticoid Receptor gene SNP with azoospermia in Japanese men. AB - AIM: The molecular pathogenesis of non-obstructive azoospermia (NOA) is unclear. Our aim was to identify the genetic susceptibility for NOA in Japanese men by using a combination of transcriptome network analysis and SNP genotyping. MATERIAL AND METHODS: We searched for candidate genes using RNA transcriptome network analysis of 2611 NOA-related genes that we had previously reported. We analyzed candidate genes for disease linkage with single nucleotide polymorphisms (SNP) in the genomes of 335 Japanese men with NOA and 410 healthy controls using SNP-specific real-time polymerase chain reaction TaqMan assays. RESULTS: Three candidate genes (NR3C1, YBX2, and BCL2) were identified by the transcriptome network analysis, each with three SNP. Allele frequency analysis of the nine SNP indicated a significantly higher frequency of the NR3C1 rs852977 G allele in NOA cases compared with controls (corrected P = 5.7e-15; odds ratio = 3.20; 95% confidence interval, 2.40-4.26). The other eight candidate polymorphisms showed no significant association. CONCLUSION: The NR3C1 rs852977 polymorphism is a potential marker for genetic susceptibility to NOA in Japanese men. Further studies are necessary to clarify the association between the NR3C1 polymorphism and alterations of glucocorticoid signaling pathway leading to male infertility. PMID- 26556221 TI - Enhancing therapeutic effects after augmentation of omega-3 fatty acid with long term antidepressant therapy in a chronic case of panic disorder. PMID- 26556220 TI - Use of Becaplermin for nondiabetic ulcers: pyoderma gangrenosum and calciphylaxis. AB - Large difficult to heal ulcers of various etiologies carry a high morbidity and mortality rate. Becaplermin is a recombinant platelet-derived growth factor approved for treatment of diabetic ulcers. In this two-case series, we report the use of becaplermin in the treatment of ulcers due to (i) calciphylaxis, an often fatal condition resulting from systemic calcification and thrombosis of vessels and (ii) pyoderma gangrenosum (PG), a neutrophilic dermatosis. We also report that topical collagenase worsened PG ulcers, consistent with pathergy. Becaplermin can be used to help treat ulcers resulting from calciphylaxis and PG. These encouraging results lend support for the utilization of becaplermin in the treatment of nondiabetic chronic ulcers of various etiologies. PMID- 26556222 TI - [Cryoablation: Clinical applications in cardiac electrophysiology from their biophysical bases]. AB - Cryoablation is an energy alternative to radiofrequency for ablation of various arrhythmias, where its unique biophysical properties offer a greater safety profile. Since its first use for the surgical treatment of different arrhythmias until its conceptualization in the current technical transcatheter, cryoablation has proven not to be only a safe source of energy, but also an effective source in the long-term. While the radiofrequency has been the energy most used for isolation of pulmonary veins in atrial fibrillation ablation, technological advances in cryoballon have managed to simplify the procedure without sacrificing its effectiveness. Cryoablation has been widely used for arrhythmias located in high-risk locations, such as the ablation of the atrioventricular nodal reentrant tachycardia and septal accessory pathways, due to its theoretical null risk of complete AV block. This review intends to give the clinical applications of the cryothermy through a thorough understanding of their biophysical basis. PMID- 26556223 TI - [Dextrocardia, aortic coarctation and coronary artery disease. A case report and review of the literature]. PMID- 26556224 TI - Temporal Levels of Urinary Neonicotinoid and Dialkylphosphate Concentrations in Japanese Women Between 1994 and 2011. AB - Over the last two decades, usage of neonicotinoid (NEO) insecticides has increased due to their high selectivity for insects versus mammals and their effectiveness for extermination of insects resistant to conventional pesticides such as pyrethroids and organophosphates (OPs). However, historical change of the NEO exposure level in humans is poorly understood. The aim of this study is to reveal changes in the levels of NEO and OP exposure in the human body over the last two decades using biomonitoring technique. We quantified urinary concentrations of 7 NEOs (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam) and 4 metabolites of OPs (dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate) in 95 adult females aged 45-75 in 1994, 2000, 2003, 2009, and 2011 (n = 17-20 different individuals in each year). The results show that the detection rates of urinary NEOs in Japanese women increased significantly between 1994 and 2011, suggesting that intakes of NEOs into the human body rose during that period. In contrast, exposure to OPs having O,O-dimethyl moieties decreased steadily according to a finding that geometric means of urinary dimethylphosphate concentrations kept diminishing considerably. These changes may reflect the amounts of NEOs and OPs used as insecticides in Japan. PMID- 26556225 TI - Gaps and gains from engaging districts stakeholders for community-based health professions education in Uganda: a qualitative study. AB - Community-based education research and service (COBERS) is a brand of community based education that has been adopted by the Medical Education and Service for All Ugandans consortium. The COBERS programme is aimed at equipping students in health professional education with the knowledge, attitudes and skills required to provide appropriate health care services. For sustainability purposes, the health professional training institutions have made efforts to involve various stakeholders in the implementation of the programme. However, the actual engagement process and outcome of such efforts have not been documented. This paper documents gaps and gains made in engaging district stakeholders for community-based education. Key informant interviews, focus group discussions and document review were used to collect data. Atlas.ti, computer software for qualitative data was used to aid analysis. The analysis revealed that the adopted engagement model has registered some gains including increased awareness among district leaders about potential opportunities offered by COBERS such as boosting of human resources at health facilities, opportunities for professional development for health care workers at health facilities, and establishment of linkages between prospective employees and employers. However, the engagement model left some gaps in terms of knowledge, awareness and ownership of the programme among some sections of stakeholders. The apparent information gap about the programme among district stakeholders, especially the political leadership, may hinder concerted partnership. The findings highlight the need for health professional education institutions to broaden the scope of actively engaged stakeholders with the district level. PMID- 26556226 TI - A pharmacogenomic study revealed an association between SLC6A4 and risperidone induced weight gain in Chinese Han population. AB - AIM: We carried out a pharmacogenomic study in order to identify susceptible genes for antipsychotics induced weight gain within the Chinese Han population. MATERIALS & METHODS: We enrolled 216 patients with schizophrenia in our study. All of them underwent risperidone monotherapy, and fulfilled 4-week follow-up. Weight gain was measured before treatment and 4 weeks later. Seven hundred and sixty-eight SNPs from 85 genes were calculated for association with weight gain percentage. RESULTS: Fifty-seven SNPs located at 16 genes with a p-value less than 0.05.4 SNPs located on serotonin transporter gene (solute carrier family 6, member 4, SLC6A4) remained significant after multitest correction (rs3813034, p = 0.000357, q = 0.08, rs1042173, rs4325622, rs9303628, p = 0.000451, q = 0.08). CONCLUSION: SLC6A4 might be susceptible gene for risperidone-induced weight gain within the Chinese Han population. PMID- 26556227 TI - Adsorption Kinetics Dictate Monolayer Self-Assembly for Both Lipid-In and Lipid Out Approaches to Droplet Interface Bilayer Formation. AB - The droplet interface bilayer (DIB)--a method to assemble planar lipid bilayer membranes between lipid-coated aqueous droplets--has gained popularity among researchers in many fields. Well-packed lipid monolayer on aqueous droplet-oil interfaces is a prerequisite for successfully assembling DIBs. Such monolayers can be achieved by two different techniques: "lipid-in", in which phospholipids in the form of liposomes are placed in water, and "lipid-out", in which phospholipids are placed in oil as inverse micelles. While both approaches are capable of monolayer assembly needed for bilayer formation, droplet pairs assembled with these two techniques require significantly different incubation periods and exhibit different success rates for bilayer formation. In this study, we combine experimental interfacial tension measurements with molecular dynamics simulations of phospholipids (DPhPC and DOPC) assembled from water and oil origins to understand the differences in kinetics of monolayer formation. With the results from simulations and by using a simplified model to analyze dynamic interfacial tensions, we conclude that, at high lipid concentrations common to DIBs, monolayer formation is simple adsorption controlled for lipid-in technique, whereas it is predominantly adsorption-barrier controlled for the lipid-out technique due to the interaction of interface-bound lipids with lipid structures in the subsurface. The adsorption barrier established in lipid-out technique leads to a prolonged incubation time and lower bilayer formation success rate, proving a good correlation between interfacial tension measurements and bilayer formation. We also clarify that advective flow expedites monolayer formation and improves bilayer formation success rate by disrupting lipid structures, rather than enhancing diffusion, in the subsurface and at the interface for lipid-out technique. Additionally, electrical properties of DIBs formed with varying lipid placement and type are characterized. PMID- 26556228 TI - Direct and indirect immunofluorescence staining patterns in the diagnosis of paraneoplastic pemphigus. PMID- 26556229 TI - Spotted in the News: Using Media Reports to Examine Leopard Distribution, Depredation, and Management Practices outside Protected Areas in Southern India. AB - There is increasing evidence of large carnivore presence outside protected areas, globally. Although this spells conservation success through population recoveries, it makes carnivore persistence in human-use landscapes tenuous. The widespread distribution of leopards in certain regions of India typifies this problem. We obtained information on leopard-human interactions at a regional scale in Karnataka State, India, based on systematic surveys of local media reports. We applied an innovative occupancy modelling approach to map their distribution patterns and identify hotspots of livestock/human depredation. We also evaluated management responses like removals of 'problem' leopards through capture and translocations. Leopards occupied around 84,000 km2 or 47% of the State's geographic area, outside designated national parks and wildlife sanctuaries. Their presence was facilitated by extent of vegetative cover- including irrigated croplands, rocky escarpments, and prey base in the form of feral and free-ranging dogs. Higher probabilities of livestock/human attacks by leopards were associated with similar ecological features as well as with capture/removals of leopards. Of the 56 cases of leopard removals reported, 91% did not involve human attacks, but followed livestock predation or only leopard sightings. The lack of knowledge on leopard ecology in human-use areas has resulted in unscientific interventions, which could aggravate the problem rather than mitigating it. Our results establish the presence of resident, breeding leopards in human-use areas. We therefore propose a shift in management focus, from current reactive practices like removal and translocation of leopards, to proactive measures that ensure safety of human lives and livelihoods. PMID- 26556231 TI - Porous Silicon Covered with Silver Nanoparticles as Surface-Enhanced Raman Scattering (SERS) Substrate for Ultra-Low Concentration Detection. AB - Microporous and macro-mesoporous silicon templates for surface-enhanced Raman scattering (SERS) substrates were produced by anodization of low doped p-type silicon wafers. By immersion plating in AgNO3, the templates were covered with silver metallic film consisting of different silver nanostructures. Scanning electron microscopy (SEM) micrographs of these SERS substrates showed diverse morphology with significant difference in an average size and size distribution of silver nanoparticles. Ultraviolet-visible-near-infrared (UV-Vis-NIR) reflection spectroscopy showed plasmonic absorption at 398 and 469 nm, which is in accordance with the SEM findings. The activity of the SERS substrates was tested using rhodamine 6G (R6G) dye molecules and 514.5 nm laser excitation. Contrary to the microporous silicon template, the SERS substrate prepared from macro-mesoporous silicon template showed significantly broader size distribution of irregular silver nanoparticles as well as localized surface plasmon resonance closer to excitation laser wavelength. Such silver morphology has high SERS sensitivity that enables ultralow concentration detection of R6G dye molecules up to 10(-15) M. To our knowledge, this is the lowest concentration detected of R6G dye molecules on porous silicon-based SERS substrates, which might even indicate possible single molecule detection. PMID- 26556230 TI - Murine versus human apolipoprotein E4: differential facilitation of and co localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models. AB - INTRODUCTION: Amyloid beta (Abeta) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer's disease (AD). Abeta also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) E4 is associated with increases in both Abeta plaques and CAA in humans. Studies in mouse models that develop Abeta deposition have shown that murine apoE and human apoE4 have different abilities to facilitate plaque or CAA formation when studied independently. To better understand and compare the effects of murine apoE and human apoE4, we bred 5XFAD (line 7031) transgenic mice so that they expressed one copy of murine apoE and one copy of human apoE4 under the control of the normal murine apoE regulatory elements (5XFAD/apoE(m/4)). RESULTS: The 5XFAD/apoE(m/4) mice contained levels of parenchymal CAA that were intermediate between 5XFAD/apoE(m/m) and 5XFAD/apoE(4/4) mice. In 5XFAD/apoE(m/4) mice, we found that Abeta parenchymal plaques co-localized with much more apoE than did parenchymal CAA, suggesting differential co-aggregation of apoE with Abeta in plaques versus CAA. More importantly, within the brain parenchyma of the 5XFAD/apoE(m/4) mice, plaques contained more murine apoE, which on its own results in more pronounced and earlier plaque formation, while CAA contained more human apoE4 which on its own results in more pronounced CAA formation. We further confirmed the co aggregation of mouse apoE with Abeta in plaques by showing a strong correlation between insoluble mouse apoE and insoluble Abeta in PS1APP-21/apoE(m/4) mice which develop plaques without CAA. CONCLUSIONS: These studies suggest that both murine apoE and human apoE4 facilitate differential opposing effects in influencing Abeta plaques versus CAA via different co-aggregation with these two amyloid lesions and set the stage for understanding these effects at a molecular level. PMID- 26556232 TI - Pincer-Nickel-Catalyzed Allyl-Aryl Coupling between Allyl Methyl Ethers and Arylzinc Chlorides. AB - The P,N,N-pincer nickel complex [Ni(Cl){N(2-Ph2PC6H4)(2'-Me2NC6H4)}]-catalyzed allyl-aryl coupling was studied. The reaction of allyl methyl ethers, including (1-methoxyallyl)arenes and (3-methoxyprop-1-en-1-yl)arenes, with arylzinc chlorides afforded linear (E)-alkenes in high yields, whereas the reaction of (E) 1-methoxytridec-2-ene with p-Me2NC6H4ZnCl generated a mixture of linear and branched alkenes. PMID- 26556233 TI - Editorial: Is the NLPR3 Inflammasome "Overheated" by Pneumococcal Vaccination in Cryopyrin-Associated Periodic Syndromes? PMID- 26556234 TI - Glycemic load, exercise, and monitoring blood glucose (GEM): A paradigm shift in the treatment of type 2 diabetes mellitus. AB - AIMS: This preliminary RCT investigated whether an integrated lifestyle modification program that focuses on reducing postprandial blood glucose through replacing high with low glycemic load foods and increasing routine physical activities guided by systematic self-monitoring of blood glucose (GEM) could improve metabolic control of adults with type 2 diabetes mellitus, without compromising other physiological parameters. METHODS: Forty-seven adults (mean age 55.3 years) who were diagnosed with type 2 diabetes mellitus for less than 5 years (mean 2.1 years), had HbA1c >= 7% (mean 8.4%) and were not taking blood glucose lowering medications, were randomized to routine care or five 1-h instructional sessions of GEM. Assessments at baseline and 6 months included a physical exam, metabolic and lipid panels, and psychological questionnaires. RESULTS: The GEM intervention led to significant improvements in HbA1c (decreasing from 8.4 to 7.4% [69-57 mmol/mol] compared with 8.3 to 8.3% [68-68 mmol/mol] for routine care; Interaction p<.01) and psychological functioning without compromising other physiological parameters. CONCLUSIONS: Consistent with a patient-centered approach, GEM appears to be an effective lifestyle modification option for adults recently diagnosed with type 2 diabetes mellitus. PMID- 26556236 TI - Unusually high soil nitrogen oxide emissions influence air quality in a high temperature agricultural region. AB - Fertilized soils have large potential for production of soil nitrogen oxide (NOx=NO+NO2), however these emissions are difficult to predict in high temperature environments. Understanding these emissions may improve air quality modelling as NOx contributes to formation of tropospheric ozone (O3), a powerful air pollutant. Here we identify the environmental and management factors that regulate soil NOx emissions in a high-temperature agricultural region of California. We also investigate whether soil NOx emissions are capable of influencing regional air quality. We report some of the highest soil NOx emissions ever observed. Emissions vary nonlinearly with fertilization, temperature and soil moisture. We find that a regional air chemistry model often underestimates soil NOx emissions and NOx at the surface and in the troposphere. Adjusting the model to match NOx observations leads to elevated tropospheric O3. Our results suggest management can greatly reduce soil NOx emissions, thereby improving air quality. PMID- 26556235 TI - A Novel Adeno-Associated Virus-Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine. AB - More than 170 million individuals worldwide are infected with hepatitis C virus (HCV), and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV) vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b. The expression of the NS3 or NS3/4 protein in HepG2 cells was confirmed by western blotting. C57BL/6 mice were intramuscularly immunised with a single injection of AAV vectors, and the resultant immune response was investigated. The AAV2/rh32.33.NS3/4 vaccine induced stronger humoral and cellular responses than did the AAV2/rh32.33.NS3 vaccine. Our results demonstrate that AAV-based vaccines exhibit considerable potential for the development of an effective anti-HCV vaccine. PMID- 26556237 TI - Captive Reptile Mortality Rates in the Home and Implications for the Wildlife Trade. AB - The trade in wildlife and keeping of exotic pets is subject to varying levels of national and international regulation and is a topic often attracting controversy. Reptiles are popular exotic pets and comprise a substantial component of the live animal trade. High mortality of traded animals raises welfare concerns, and also has implications for conservation if collection from the wild is required to meet demand. Mortality of reptiles can occur at any stage of the trade chain from collector to consumer. However, there is limited information on mortality rates of reptiles across trade chains, particularly amongst final consumers in the home. We investigated mortality rates of reptiles amongst consumers using a specialised technique for asking sensitive questions, additive Randomised Response Technique (aRRT), as well as direct questioning (DQ). Overall, 3.6% of snakes, chelonians and lizards died within one year of acquisition. Boas and pythons had the lowest reported mortality rates of 1.9% and chameleons had the highest at 28.2%. More than 97% of snakes, 87% of lizards and 69% of chelonians acquired by respondents over five years were reported to be captive bred and results suggest that mortality rates may be lowest for captive bred individuals. Estimates of mortality from aRRT and DQ did not differ significantly which is in line with our findings that respondents did not find questions about reptile mortality to be sensitive. This research suggests that captive reptile mortality in the home is rather low, and identifies those taxa where further effort could be made to reduce mortality rates. PMID- 26556238 TI - SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells. AB - The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int) appeared to globally undergo tyrosine dephosphorylation. In parallel, expression of the cytoplasmic protein tyrosine phosphatase Src homology-2 domain-containing phosphatase 2 (SHP-2) increased in a time-dependent manner. SHP-2 co-localized with the C. parvum sporozoite and this interaction increased the rate of C. parvum infectivity through SH2-mediated SHP 2 activity. Furthermore, we show that one potential target that SHP-2 acts upon is the focal adhesion protein, paxillin, which undergoes moderate dephosphorylation following infection, with inhibition of SHP-2 rescuing paxillin phosphorylation. Importantly, treatment with an inhibitor to SHP-2 and with an inhibitor to paxillin and Src family kinases, effectively decreased the multiplicity of C. parvum infection in a dose-dependent manner. Thus, our study reveals an important role for SHP-2 in the pathogenesis of C. parvum. Furthermore, while host proteins can be recruited to participate in the development of the electron dense band at the host cell-parasite interface, our study implies for the first time that SHP-2 appears to be recruited by the C. parvum sporozoite to regulate infectivity. Taken together, these findings suggest that SHP-2 and its down-stream target paxillin could serve as targets for intervention. PMID- 26556239 TI - Diagnostic Ureterorenoscopy Is Associated with Increased Intravesical Recurrence following Radical Nephroureterectomy in Upper Tract Urothelial Carcinoma. AB - Diagnostic ureterorenoscopy is powerful tool to confirm upper tract urothelial cancer (UTUC). However, URS and associated manipulation may be related to the risk of intravesical recurrence (IVR) following radical nephroureterectomy (RNU). We aimed to investigate whether preoperative ureterorenoscopy would increase IVR after RNU in patients with UTUC. We performed a retrospective analysis of 630 patients who had RNU with bladder cuff excision due to UTUC. Diagnostic URS was performed in 282 patients (44.7%). Patients were divided into two groups according to the URS. Survival analysis and multivariate Cox regression model were performed to address risk factors for the IVR. The interval from URS to RNU was measured. During URS, manipulation such as biopsy and resection was determined. The median age was 64 (IQR 56-72) years with follow-up duration of 34.3 (15.7-64.9) months. Median time from URS to RNU was 16 (0-38) days. The IVR developed in 42.5% (n = 268) patients at 8.2 (4.9-14.7) months. The five-year IVR free survival rate was 42.6 +/- 8.0% and 63.6 +/- 6.9% in patients with and without preoperative URS, respectively (P < 0.001). In multivariate analysis, previous history of bladder tumour, extravesical excision of distal ureter, multifocal tumour, and URS (HR, 95% CI; 1.558, 1.204-2.016, P = 0.001) were independent predictors for higher IVR. The IVR rate in patients without manipulation during URS was not different to those with manipulation (P = 0.658). The duration from URS to RNU was not associated with IVR (P = 0.799). Diagnostic URS for UTUC increased IVR rate after RNU. However, the lessening of interval from URS to radical surgery or URS without any manipulation could not reduce the IVR rate. PMID- 26556240 TI - Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia. AB - It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID- 26556241 TI - TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury. AB - Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays an important role in the pathogenesis of hypertension and renal fibrosis. Toll-like receptor 4 (TLR4) signaling contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced hypertension and renal damage is not clear. In the current study, rats were treated with Aldo-salt combined with TAK 242 (a TLR4 signaling antagonist) for 4 weeks. Hemodynamic, cardiac and renal parameters were assayed at the indicated time. We found that Aldo-salt-treated rats present cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of TLR4 as well as levels of molecular markers attesting inflammation and fibrosis are increased by Aldo infusion, whereas the treatment of TAK-242 reverses these alterations. TAK-242 suppresses cardiac and renal inflammatory cytokines levels (TNF-a, IL-1beta and MCP-1). Furthermore, TAK-242 inhibits hypertension, cardiac and renal fibrosis, and also attenuates the Aldo induced Epithelial-Mesenchymal Transition (EMT). In experimental hyperaldosteronism, upregulation of TLR4 is correlated with cardiac and renal fibrosis and dysfunction, and a TLR4 signaling antagonist, TAK-242, can reverse these alterations. TAK-242 may be a therapeutic option for salt-sensitive hypertension and renal fibrosis. PMID- 26556244 TI - Special Care Dentistry - An Evolving Aspect of Dentistry. PMID- 26556242 TI - Integrative Genomics Implicates EGFR as a Downstream Mediator in NKX2-1 Amplified Non-Small Cell Lung Cancer. AB - NKX2-1, encoding a homeobox transcription factor, is amplified in approximately 15% of non-small cell lung cancers (NSCLC), where it is thought to drive cancer cell proliferation and survival. However, its mechanism of action remains largely unknown. To identify relevant downstream transcriptional targets, here we carried out a combined NKX2-1 transcriptome (NKX2-1 knockdown followed by RNAseq) and cistrome (NKX2-1 binding sites by ChIPseq) analysis in four NKX2-1-amplified human NSCLC cell lines. While NKX2-1 regulated genes differed among the four cell lines assayed, cell proliferation emerged as a common theme. Moreover, in 3 of the 4 cell lines, epidermal growth factor receptor (EGFR) was among the top NKX2 1 upregulated targets, which we confirmed at the protein level by western blot. Interestingly, EGFR knockdown led to upregulation of NKX2-1, suggesting a negative feedback loop. Consistent with this finding, combined knockdown of NKX2 1 and EGFR in NCI-H1819 lung cancer cells reduced cell proliferation (as well as MAP-kinase and PI3-kinase signaling) more than knockdown of either alone. Likewise, NKX2-1 knockdown enhanced the growth-inhibitory effect of the EGFR inhibitor erlotinib. Taken together, our findings implicate EGFR as a downstream effector of NKX2-1 in NKX2-1 amplified NSCLC, with possible clinical implications, and provide a rich dataset for investigating additional mediators of NKX2-1 driven oncogenesis. PMID- 26556246 TI - Special Care Dentistry - Drilling Down to the Detail. PMID- 26556243 TI - Integrative enrichment analysis: a new computational method to detect dysregulated pathways in heterogeneous samples. AB - BACKGROUND: Pathway enrichment analysis is a useful tool to study biology and biomedicine, due to its functional screening on well-defined biological procedures rather than separate molecules. The measurement of malfunctions of pathways with a phenotype change, e.g., from normal to diseased, is the key issue when applying enrichment analysis on a pathway. The differentially expressed genes (DEGs) are widely focused in conventional analysis, which is based on the great purity of samples. However, the disease samples are usually heterogeneous, so that, the genes with great differential expression variance (DEVGs) are becoming attractive and important to indicate the specific state of a biological system. In the context of differential expression variance, it is still a challenge to measure the enrichment or status of a pathway. To address this issue, we proposed Integrative Enrichment Analysis (IEA) based on a novel enrichment measurement. RESULTS: The main competitive ability of IEA is to identify dysregulated pathways containing DEGs and DEVGs simultaneously, which are usually under-scored by other methods. Next, IEA provides two additional assistant approaches to investigate such dysregulated pathways. One is to infer the association among identified dysregulated pathways and expected target pathways by estimating pathway crosstalks. The other one is to recognize subtype factors as dysregulated pathways associated to particular clinical indices according to the DEVGs' relative expressions rather than conventional raw expressions. Based on a previously established evaluation scheme, we found that, in particular cohorts (i.e., a group of real gene expression datasets from human patients), a few target disease pathways can be significantly high-ranked by IEA, which is more effective than other state-of-the-art methods. Furthermore, we present a proof-of-concept study on Diabetes to indicate: IEA rather than conventional ORA or GSEA can capture the under-estimated dysregulated pathways full of DEVGs and DEGs; these newly identified pathways could be significantly linked to prior-known disease pathways by estimated crosstalks; and many candidate subtype-factors recognized by IEA also have significant relation with the risk of subtypes of genotype-phenotype associations. CONCLUSIONS: Totally, IEA supplies a new tool to carry on enrichment analysis in the complicate context of clinical application (i.e., heterogeneity of disease), as a necessary complementary and cooperative approach to conventional ones. PMID- 26556247 TI - Dean's Update: A Bold New Tomorrow. PMID- 26556248 TI - Membership Affairs. PMID- 26556249 TI - Policy Update: Towards Better Regulation in Cosmetic Practice Post-Keogh. PMID- 26556250 TI - Five Minutes with Dean-Elect Mick Horton. PMID- 26556251 TI - Foundation Dentists Open Day. PMID- 26556252 TI - FGDP(UK) Divisional Update: Contemporary Periodontal and Peri-implant Management. PMID- 26556253 TI - My Dental Experience - Special Care Patients' Views. PMID- 26556254 TI - Managing Bariatric Patients in Dentistry. AB - Obesity is a growing issue across the world, presenting a range of challenges to society. Management of obese or bariatric patients in the dental environment has become more commonplace. This article considers an overview of obesity, reviews its dental impact and offers some solutions to minimising those challenges in the dental setting. PMID- 26556255 TI - A Care Pathway for Children Unable to Accept Dental Care Within the General Dental Services Involving the Use of Inhalation Sedation and General Anaesthesia. AB - Dental treatment is the commonest reason for a child to be in hospital in the UK. This is a shocking statistic for a preventable disease. How can we reduce the high numbers of dental general anaesthetics? It is essential that dental treatment under general anaesthesia (GA) is fully justifiable, ensuring that the right patients receive the right treatment. Guidance for general dental practitioners on when to refer a child for a dental GA is discussed. Treatment planning for this dentally high-risk group of children requires a holistic approach. It is complex and requires an experienced and competent clinical team, including dental care professionals with additional postgraduate qualifications. Often, alternative treatments are successful and a GA can be avoided. An audit of 85 patients referred for GA with Oldham Community Dental Service demonstrated 35% of patients accepted treatment with local anaesthesia only, 25% required inhalation sedation and only 25% were actually referred on for GA. Treatment for this group of patients must include the availability and provision of appropriate alternative treatment modalities, with the right staff and facilities, including those for dental general anaesthetic sessions. Ongoing follow-up within the general dental services is essential for this group of patients. PMID- 26556256 TI - Are Dental Implants the Answer to Tooth Loss in Patients with Parkinson's Disease? AB - Individuals with Parkinson's disease present a challenge to dental clinicians as this degenerative disease leads to problems accessing care and maintaining an adequate level of oral health. This article provides an overview of the implications of Parkinson's disease on oral health and explores the role of dental implants in the management of such patients. PMID- 26556257 TI - The Use of Intranasal Midazolam in a Special Care Dentistry Department: Technique and Cases. AB - Intranasal (IN) administered midazolam has allowed patients who require conscious sedation but struggle to tolerate cannulation another option by which they can receive dental treatment. Studies have demonstrated that a mean bioavailability (F) of more than 73% can be achieved with IN-administered midazolam. This is due to the high vascularity within the nose. These studies have also demonstrated that peak plasma concentrations can be reached within 10 minutes. This signifies a fast onset of action. The standard bolus dose of IN midazolam is 10mg; this bolus can be reduced or increased depending on the patient's age and susceptibility to benzodiazepines. The bolus can also be repeated if adequate sedation is not reached. A protocol for administering IN midazolam is outlined and two cases are discussed. PMID- 26556258 TI - Psychoactive Substance Dependence: A Dentist's Challenge. AB - Given the number of individuals who are dependent on alcohol and/or drugs, it is inevitable that they will present for dental treatment. They are at an increased risk of dental disease for multiple reasons. This paper aims to provide an overview for general dental practitioners (GDPs) of the challenges that can arise in treating such patients, alongside some suggestions for meeting these challenges. General issues are taken into consideration first, then a focus is made on each of the most common substances, together with their implications in dentistry. PMID- 26556259 TI - Dental Management of Patients with Dementia in Primary Dental Care. AB - Dementia is an umbrella term for a set of symptoms that include memory loss, changes in mood and problems with reasoning, attention and communication. It is a progressive condition and there is ample evidence that oral health declines as the severity of dementia increases. Most of this decline is attributable to the effects of cognitive impairment on oral hygiene capability and/or acceptance of help from others in supporting oral hygiene. Factors such as altered salivary flow, taste change, use of high-energy food supplements and syrup-based medications also contribute to the risk of oral and dental diseases. In its role as part of the wider health and social care network, the primary dental care team can make an important contribution to securing the oral health of people living with dementia. PMID- 26556260 TI - Learning from a Special Care Dentistry Needs Assessment. AB - The General Dental Council recognised special care dentistry (SCD) as a speciality in 2008 and local service reviews have been carried out in order to develop SCD services. A needs assessment was completed to inform the implementation of recommendations from a 2010 review of SCD in Wales. AIM: The aim of this paper is to outline the process, findings and learning from the needs assessment and the implications for SCD. METHOD: A focused needs assessment approach was used. Stakeholder consultations were used to develop a working definition for the needs assessment. Data were collected from existing health and social care sources and analysed using descriptives and geographic information system (GIS) mapping. RESULTS: Data sources for needs assessment were limited. Analysis showed that health conditions were common in the population and increased with age. The majority of people who reported seeing a dentist were seen in general dental practice. Older people with health conditions were less likely to report seeing a dentist. Patients often needed to travel for specialist care services. CONCLUSION: General dental practice teams have a significant role in caring for SCD patients. Careful planning of specialist care, joint working and enhancing skills across the general practice team will reduce the burden of care and enhance patient safety. Improvements in data for assessment of SCD needs are required to help this process. PMID- 26556261 TI - Capacity, Consent and Dentistry - Who Decides and How Do They Do It? AB - Dental interventions can only occur within a legal framework. This means either the patient gives their informed consent to the procedure or, if this is not possible, an assessment is made whether they lack the ability to consent, in which case a decision on treatment is made under the Mental Capacity Act (MCA). This article takes a brief look at how the MCA sets out the test of capacity, who makes decisions when the patient is unable to do so and how 'best interest' decisions are made in a way that protects the rights of the patient and protects the dental professional from legal liability. PMID- 26556262 TI - Giving a Voice to the Person in My Dental Chair: Communication with People with Learning Disabilities. AB - This article aims to increase the dental teams' awareness of communicating with people with learning disabilities who have additional communication impairments. The paper presents a brief account of the factors behind why some people with learning disabilities may find it difficult to verbally communicate, and highlights the importance of ensuring high levels of care for all patients. It provides an overview of the principles of communication development and some of the most commonly used augmentative and alternative communication approaches. The paper concludes with suggestions of simple communication techniques as well as practical ideas, which can be easily incorporated into daily general dental practice in order to increase opportunities for successful interactions and minimise communication breakdown. By becoming more aware of the range of communication methods used to support those who have learning disabilities, the dental team will be more able to provide a better experience to their patients and ensure that their needs are met. PMID- 26556263 TI - A Case Report for a Complex Denture Case on a Special Care Patient with Osteogenesis Imperfecta. AB - This case report presents a patient with Dentogenesis Imperfecta (DI) associated with Osteogenesis Imperfecta (OI) and its subsequent dental manifestations. The patient in this report (see Figure 1) has spent his life living with his disability type III OI (also known as brittle bone disease) and its degenerative affects. The patient is independent and enjoys his social life but felt his existing dentures were having an adverse effect on the quality of his life. The patient attended Dorset County Hospitals Special Care Dentistry and on clinical examination it was noted the patient was partially dentate with a class III malocclusion and brownish discoloration of the remaining teeth caused by enamel hypoplasia. Treatment for this patient would entail making a maxillary complete denture and a mandibular partial chrome denture, normally quite simple tasks but due to the DI and its dental manifestations, the treatment would be complicated. This case demonstrates how a complex case treated by a collaborative dental team using their different skills and knowledge can lead to a successful and rewarding treatment for both patient and team. PMID- 26556264 TI - Special Care Dentistry: Experiences of a DCP. PMID- 26556266 TI - [Leiomyomatous renal cell carcinoma : Controversy around a new entity]. AB - While clear cell, papillary and chromophobic renal cell carinoma (RCC) represent the most common malignant renal neoplasms, the evaluation and classification of rare renal carcinomas has currently come into focus. One of these is the leiomyomatous RCC, which shows morphologic similarities to clear cell RCCs, however exhibiting additional, atypical smooth muscle differentiation. We report the clinical case of a patient simultaneously presenting with leiomyomatous and papillary RCC and discuss new tumor entities of RCC. PMID- 26556267 TI - [Social freezing - the male perspective]. AB - BACKGROUND: In Germany there is an emerging trend for postponing parenthood due to non-medical, sociocultural reasons. This clearly impacts on the reproductive success due to an age-dependent decrease in fertility. Thus, strategies and techniques are currently discussed which could preserve the female fertility status, among which social freezing (cryopreservation of oocytes) for later fertilization is the most realistic one; however, while there is an intensive discussion on the procedure and timing of oocyte cryopreservation, virtually no attention has been paid to the male side and the aging effects on the male germ cells. AIM: To evaluate the risk paternal age poses for the integrity of germ cells. METHODS: For this review a literature search using PubMed, data from the Federal Statistical Office of Germany, the German in vitro fertilization (IVF) register as well as own data were used. RESULTS: Sperm cell integrity is clearly affected by age both at the genetic as well as at the epigenetic levels. The estimated mutation rate for spermatozoa doubles every 16.5 years. Monogenic and multifactorial diseases are strongly associated with paternal age. Men aged >40 years have an increased risk of passing age-related mutations to their children. CONCLUSIONS: Cryopreservation of spermatozoa is an option for men who postpone planning a family. Genetic counseling is recommended for couples undertaking social freezing and a male age of >40 years. PMID- 26556268 TI - [Value of MRI/ultrasound fusion in primary biopsy for the diagnosis of prostate cancer]. AB - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) plays an emerging role in prostate cancer diagnosis. We compared the cancer detection rates of targeted biopsy (tB) of suspicious lesions in mpMRI versus systematic transperineal saturation biopsy (sB) in men with primary suspicion of prostate cancer (PCa). METHODS: A total of 437 consecutive primary biopsy patients, who underwent transperineal systematic and fusion-guided biopsy between 2012 and 2014, were enrolled. mpMRI was evaluated based on PI-RADS. Analysis of biopsy specimen was performed following START criteria. RESULTS: Of the 437 men, 334 harbored 426 MR lesions. Overall, 274 PCa and 203 significant PCa (Gleason score (GS) >= 3 + 4, GS = 3 + 3 and PSA values >= 10 ng/ml) were detected. There were 52 (26 %) significant PCa exclusively found by sB, whereas only 18 (9 %) were identified by tB (p < 0.001). Of 80 high-grade PCa with GS >= 4 + 3, 70 were diagnosed by sB, and 60 by tB (p = 0.007). In addition, 54 % of all insignificant PCa (GS < 7, PSA < 10 ng/ml) were detected by sB alone (p < 0.001). AUC of mpMRI was 0.76-0.78. CONCLUSION: The combination of tB + sB detects PCa most accurately. Ongoing prospective (multicenter) studies are evaluating the status of the 12 core TRUS-guided random biopsy. PMID- 26556269 TI - [YB-1-based virotherapy: A new therapeutic intervention for transitional cell carcinoma of the bladder?]. AB - Therapeutic intervention using oncolytic viruses is called virotherapy. This type of virus is defined by the ability to replicate in tumor cells only and to destroy these cells upon replication. In addition, this virus type is able to induce a tumor-directed immune response. Early clinical trials have confirmed the safety profile of oncolytic viruses. Currently, different groups are working on the development of oncolytic viruses with a focus on treatment of nonmuscle invasive bladder cancer (NMIBC). A preliminary active recruiting clinical phase II/III trial ongoing in patients with a NMIBC was recently implemented in the United States. Our research group developed an oncolytic adenovirus that will soon enter a clinical phase I trial in patients diagnosed with glioma. This virus is being further modified for the treatment of NMIBC. In this review article, recent developments in the design and use of virotherapy in bladder cancer are summarized. PMID- 26556270 TI - Adipose Tissue Oxygenation in Obesity: A Matter of Cardiovascular Risk? AB - Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tissue function, historically considered as a passive fat storage. It is now well established that adipose tissue is an organ with an active role in production and release of a variety of molecules called adipocytokines. Dysregulated production of adipocytokines seems to be responsible for the pathogenesis of insulin resistance and type 2 diabetes; however, the mechanisms are still unclear. Hypoxia, that occurs when adipocytes expand in obesity, has been proposed as a possible cause of adipose tissue inflammation. On the other hand, recent studies have shown that adipose tissue oxygen tension was actually higher (hyperoxia) than normal and associated with insulin resistance in obesity, despite a reduction in blood flow. This might be explained by the role of mitochondrial oxygen consumption. Hence, further studies are needed to understand the role of adipose tissue oxygenation and perfusion in obesity to assess pathophysiology and novel opportunities for treating the diseases. PMID- 26556271 TI - Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. AB - Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. Repression of mucin glycan responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. IMPORTANCE: Human intestinal microorganisms impact many aspects of health and disease, including digestion and the propensity to develop disorders such as inflammation and colon cancer. Complex carbohydrates are a major component of the intestinal habitat, and numerous species have evolved and refined strategies to compete for these coveted nutrients. Our findings reveal that individual bacteria exhibit different preferences for carbohydrates emanating from host diet and mucosal secretions and that some of these prioritization strategies are opposite to one another. Thus, we reveal new aspects of how individual bacteria, some with otherwise similar metabolic potential, partition to "preferred niches" in the complex gut ecosystem, which has important and immediate implications for understanding and predicting the behavioral dynamics of this community. PMID- 26556272 TI - Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of Enterococcus faecium from the Intestinal Epithelium. AB - The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria, a phenomenon termed colonization resistance. Antibiotics create dysbiosis of microbiota, thereby decreasing colonization resistance and facilitating infections caused by antibiotic-resistant bacteria. Here we describe how cephalosporin antibiotics create dysbiosis in the mouse large intestine, allowing intestinal outgrowth of antimicrobial-resistant Enterococcus faecium. This is accompanied by a reduction of the mucus-associated gut microbiota layer, colon wall, and Muc-2 mucus layer. E. faecium agglutinates intraluminally in an extracellular matrix consisting of secretory IgA (sIgA), polymeric immunoglobulin receptor (pIgR), and epithelial cadherin (E-cadherin) proteins, thereby maintaining spatial segregation of E. faecium from the intestinal wall. Addition of recombinant E-cadherin and pIgR proteins or purified IgA to enterococci in vitro mimics agglutination of E. faecium in vivo. Also, the Ca(2+) levels temporarily increased by 75% in feces of antibiotic-treated mice, which led to deformation of E-cadherin adherens junctions between colonic intestinal epithelial cells and release of E-cadherin as an extracellular matrix entrapping E. faecium. These findings indicate that during antibiotic-induced dysbiosis, the intestinal epithelium stays separated from an invading pathogen through an extracellular matrix in which sIgA, pIgR, and E-cadherin are colocalized. Future mucosal vaccination strategies to control E. faecium or other opportunistic pathogens may prevent multidrug-resistant infections, hospital transmission, and outbreaks. IMPORTANCE: Infections with antibiotic-resistant enterococci are an emerging worldwide problem because enterococci are resistant to most of the antibiotics used in hospitals. During antibiotic treatment, the normal bacteria are replaced by resistant enterococci within the gut, from which they can spread and cause infections. We studied antibiotic-mediated intestinal proliferation of multidrug-resistant Enterococcus faecium and the effects on intestinal architecture. We demonstrated that antibiotics allow proliferation of E. faecium in the gut, alter the mucus associated gut bacterial layer, and reduce the colon wall, mucus thickness, and amount of Muc-2 protein. E. faecium is agglutinated in the intestine in a matrix consisting of host molecules. We hypothesize that this matrix maintains a segregation of E. faecium from the epithelium. Understanding the processes that occur in the gut during antibiotic treatment may provide clues for future mucosal vaccination strategies to control E. faecium or other multidrug-resistant opportunistic pathogens, thereby preventing infections, hospital transmission, and outbreaks. PMID- 26556273 TI - Chlamydial Lytic Exit from Host Cells Is Plasmid Regulated. AB - Chlamydia trachomatis is an obligate intracellular bacterium that is a globally important human pathogen. The chlamydial plasmid is an attenuating virulence factor, but the molecular basis for attenuation is not understood. Chlamydiae replicate within a membrane-bound vacuole termed an inclusion, where they undergo a biphasic developmental growth cycle and differentiate from noninfectious into infectious organisms. Late in the developmental cycle, the fragile chlamydia laden inclusion retains its integrity by surrounding itself with scaffolds of host cytoskeletal proteins. The ability of chlamydiae to developmentally free themselves from this cytoskeleton network is a fundamental virulence trait of the pathogen. Here, we show that plasmidless chlamydiae are incapable of disrupting their cytoskeletal entrapment and remain intracellular as stable mature inclusions that support high numbers of infectious organisms. By using deletion mutants of the eight plasmid-carried genes (Deltapgp1 to Deltapgp8), we show that Pgp4, a transcriptional regulator of multiple chromosomal genes, is required for exit. Exit of chlamydiae is dependent on protein synthesis and is inhibited by the compound C1, an inhibitor of the type III secretion system (T3S). Exit of plasmid-free and Deltapgp4 organisms, which failed to lyse infected cells, was rescued by latrunculin B, an inhibitor of actin polymerization. Our findings describe a genetic mechanism of chlamydial exit from host cells that is dependent on an unknown pgp4-regulated chromosomal T3S effector gene. IMPORTANCE: Chlamydia's obligate intracellular life style requires both entry into and exit from host cells. Virulence factors that function in exiting are unknown. The chlamydial inclusion is stabilized late in the infection cycle by F-actin. A prerequisite of chlamydial exit is its ability to disassemble actin from the inclusion. We show that chlamydial plasmid-free organisms, and also a plasmid gene protein 4 (pgp4) null mutant, do not disassociate actin from the inclusion and fail to exit cells. We further provide evidence that Pgp4-regulated exit is dependent on the chlamydial type III secretion system. This study is the first to define a genetic mechanism that functions in chlamydial lytic exit from host cells. The findings also have practical implications for understanding why plasmid-free chlamydiae are highly attenuated and have the ability to elicit robust protective immune responses. PMID- 26556274 TI - Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii. AB - The increasing emergence of antibiotic-resistant bacterial pathogens represents a serious risk to human health and the entire health care system. Many currently circulating strains of Acinetobacter baumannii exhibit resistance to multiple antibiotics. A key limitation in combating A. baumannii is that our understanding of the molecular mechanisms underlying the pathogenesis of A. baumannii is lacking. To identify potential virulence determinants of a contemporary multidrug resistant isolate of A. baumannii, we used transposon insertion sequencing (TnSeq) of strain AB5075. A collection of 250,000 A. baumannii transposon mutants was analyzed for growth within Galleria mellonella larvae, an insect-based infection model. The screen identified 300 genes that were specifically required for survival and/or growth of A. baumannii inside G. mellonella larvae. These genes encompass both known, established virulence factors and several novel genes. Among these were more than 30 transcription factors required for growth in G. mellonella. A subset of the transcription factors was also found to be required for resistance to antibiotics and environmental stress. This work thus establishes a novel connection between virulence and resistance to both antibiotics and environmental stress in A. baumannii. IMPORTANCE: Acinetobacter baumannii is rapidly emerging as a significant human pathogen, largely because of disinfectant and antibiotic resistance, causing lethal infection in fragile hosts. Despite the increasing prevalence of infections with multidrug-resistant A. baumannii strains, little is known regarding not only the molecular mechanisms that allow A. baumannii to resist environmental stresses (i.e., antibiotics and disinfectants) but also how these pathogens survive within an infected host to cause disease. We employed a large-scale genetic screen to identify genes required for A. baumannii to survive and grow in an insect disease model. While we identified many known virulence factors harbored by A. baumannii, we also discovered many novel genes that likely play key roles in A. baumannii survival of exposure to antibiotics and other stress-inducing chemicals. These results suggest that selection for increased resistance to antibiotics and environmental stress may inadvertently select for increased virulence in A. baumannii. PMID- 26556275 TI - Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces. AB - Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body. IMPORTANCE: Many health care professionals use antibiotic prophylaxis strategies to prevent infection after surgery. This practice is under debate since it enhances the spread of antibiotic resistance. Another important reason to avoid nonessential use of antibiotics, the impact on our microbiome, has hardly received attention. In this study, we assessed the impact of antibiotics on the human microbial ecology at two niches. We followed the oral and gut microbiomes in 66 individuals from before, immediately after, and up to 12 months after exposure to different antibiotic classes. The salivary microbiome recovered quickly and was surprisingly robust toward antibiotic-induced disturbance. The fecal microbiome was severely affected by most antibiotics: for months, health-associated butyrate producing species became strongly underrepresented. Additionally, there was an enrichment of genes associated with antibiotic resistance. Clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome. PMID- 26556276 TI - Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials. AB - The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health. IMPORTANCE: Respiratory viruses are responsible for more deaths globally than any other infectious agent. Animal coronaviruses that "host jump" to humans result in severe infections with high mortality, such as severe acute respiratory syndrome (SARS) and, more recently, Middle East respiratory syndrome (MERS). We show here that a closely related human coronavirus, 229E, which causes upper respiratory tract infection in healthy individuals and serious disease in patients with comorbidities, remained infectious on surface materials common to public and domestic areas for several days. The low infectious dose means that this is a significant infection risk to anyone touching a contaminated surface. However, rapid inactivation, irreversible destruction of viral RNA, and massive structural damage were observed in coronavirus exposed to copper and copper alloy surfaces. Incorporation of copper alloy surfaces in conjunction with effective cleaning regimens and good clinical practice could help to control transmission of respiratory coronaviruses, including MERS and SARS. PMID- 26556277 TI - In Vitro CRISPR/Cas9 System for Efficient Targeted DNA Editing. AB - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein 9 (Cas9) system, an RNA-guided nuclease for specific genome editing in vivo, has been adopted in a wide variety of organisms. In contrast, the in vitro application of the CRISPR/Cas9 system has rarely been reported. We present here a highly efficient in vitro CRISPR/Cas9-mediated editing (ICE) system that allows specific refactoring of biosynthetic gene clusters in Streptomyces bacteria and other large DNA fragments. Cleavage by Cas9 of circular pUC18 DNA was investigated here as a simple model, revealing that the 3'->5' exonuclease activity of Cas9 generates errors with 5 to 14 nucleotides (nt) randomly missing at the editing joint. T4 DNA polymerase was then used to repair the Cas9-generated sticky ends, giving substantial improvement in editing accuracy. Plasmid pYH285 and cosmid 10A3, harboring a complete biosynthetic gene cluster for the antibiotics RK-682 and holomycin, respectively, were subjected to the ICE system to delete the rkD and homE genes in frame. Specific insertion of the ampicillin resistance gene (bla) into pYH285 was also successfully performed. These results reveal the ICE system to be a rapid, seamless, and highly efficient way to edit DNA fragments, and a powerful new tool for investigating and engineering biosynthetic gene clusters. IMPORTANCE: Recent improvements in cloning strategies for biosynthetic gene clusters promise rapid advances in understanding and exploiting natural products in the environment. For manipulation of such biosynthetic gene clusters to generate valuable bioactive compounds, efficient and specific gene editing of these large DNA fragments is required. In this study, a highly efficient in vitro DNA editing system has been established. When combined with end repair using T4 DNA polymerase, Cas9 precisely and seamlessly catalyzes targeted editing, including in-frame deletion or insertion of the gene(s) of interest. This in vitro CRISPR editing (ICE) system promises a step forward in our ability to engineer biosynthetic pathways. PMID- 26556279 TI - Probing the Viromic Frontiers. AB - Modern molecular technology, and particularly high-throughput sequencing (HTS), has revolutionized virus discovery and expanded the depth and breadth of the virome. Recent HTS was used to identify and discover a previously undescribed member of the family Flaviviridae that has genomic features characteristic of both hepaciviruses and pegiviruses. This virus, designated human hepegivirus-1 (HHpgV-1), may represent a previously undescribed new genus in the Flaviviridae family with implications for public health and blood supply safety. Detecting uncharacterized viruses such as HHpgV-1 in clinical samples requires an unbiased screening method that is as sensitive as PCR, while simultaneously detecting multiple rare viral sequences. The virome-capture-sequencing platform for vertebrate viruses (VirCapSeq-VERT) uses positive-selection oligonucleotide capture to sensitively detect sequences from every known vertebrate virus, even in high-background specimens with low-abundance viruses. VirCapSeq-VERT can also detect uncharacterized viruses with sequence homology to known viruses, enabling a new paradigm for virus detection. PMID- 26556278 TI - Riboflavin Provisioning Underlies Wolbachia's Fitness Contribution to Its Insect Host. AB - Endosymbiotic bacteria of the genus Wolbachia represent the most successful symbiotic bacteria in the terrestrial ecosystem. The success of Wolbachia has been ascribed to its remarkable phenotypic effects on host reproduction, such as cytoplasmic incompatibility, whereby maternally inherited bacteria can spread in their host populations at the expense of their host's fitness. Meanwhile, recent theoretical as well as empirical studies have unveiled that weak and/or conditional positive fitness effects may significantly facilitate invasion and spread of Wolbachia infections in host populations. Here, we report a previously unrecognized nutritional aspect, the provision of riboflavin (vitamin B2), that potentially underpins the Wolbachia-mediated fitness benefit to insect hosts. A comparative genomic survey for synthetic capability of B vitamins revealed that only the synthesis pathway for riboflavin is highly conserved among diverse insect-associated Wolbachia strains, while the synthesis pathways for other B vitamins were either incomplete or absent. Molecular phylogenetic and genomic analyses of riboflavin synthesis genes from diverse Wolbachia strains revealed that, in general, their phylogenetic relationships are concordant with Wolbachia's genomic phylogeny, suggesting that the riboflavin synthesis genes have been stably maintained in the course of Wolbachia evolution. In rearing experiments with bedbugs (Cimex lectularius) on blood meals in which B vitamin contents were manipulated, we demonstrated that Wolbachia's riboflavin provisioning significantly contributes to growth, survival, and reproduction of the insect host. These results provide a physiological basis upon which Wolbachia mediated positive fitness consequences are manifested and shed new light on the ecological and evolutionary relevance of Wolbachia infections. IMPORTANCE: Conventionally, Wolbachia has been regarded as a parasitic bacterial endosymbiont that manipulates the host insect's reproduction in a selfish manner, which tends to affect a host's fitness negatively. Meanwhile, some theories predict that, at the same time, Wolbachia can directly affect the host's fitness positively, which may potentially reconcile the negative effect and facilitate spread and stability of the symbiotic association. Here we demonstrate, by using comparative genomic and experimental approaches, that among synthetic pathways for B vitamins, the synthetic pathway for riboflavin (vitamin B2) is exceptionally conserved among diverse insect-associated Wolbachia strains, and Wolbachia's riboflavin provisioning certainly contributes to growth, survival, and reproduction in an insect. These findings uncover a nutritional mechanism of a Wolbachia-mediated fitness benefit, which provides empirical evidence highlighting a "Jekyll and Hyde" aspect of Wolbachia infection. PMID- 26556280 TI - Simple Genome Editing of Rodent Intact Embryos by Electroporation. AB - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated (Cas) system is a powerful tool for genome editing in animals. Recently, new technology has been developed to genetically modify animals without using highly skilled techniques, such as pronuclear microinjection of endonucleases. Technique for animal knockout system by electroporation (TAKE) method is a simple and effective technology that produces knockout rats by introducing endonuclease mRNAs into intact embryos using electroporation. Using TAKE method and CRISPR/Cas system, the present study successfully produced knockout and knock-in mice and rats. The mice and rats derived from embryos electroporated with Cas9 mRNA, gRNA and single-stranded oligodeoxynucleotide (ssODN) comprised the edited targeted gene as a knockout (67% of mice and 88% of rats) or knock-in (both 33%). The TAKE method could be widely used as a powerful tool to produce genetically modified animals by genome editing. PMID- 26556281 TI - High-Resolution Melting Curve Analysis for Identification of Pasteurellaceae Species in Experimental Animal Facilities. AB - Pasteurellaceae are among the most prevalent bacterial pathogens isolated from mice housed in experimental animal facilities. Reliable detection and differentiation of Pasteurellaceae are essential for high-quality health monitoring. In this study, we combined a real-time PCR assay amplifying a variable region in the 16S rRNA sequence with high-resolution melting curve analysis (HRM) to identify and differentiate among the commonly isolated species Pasteurella pneumotropica biotypes "Jawetz" and "Heyl", Actinobacillus muris, and Haemophilus influenzaemurium. We used a set of six reference strains for assay development, with the melting profiles of these strains clearly distinguishable due to DNA sequence variations in the amplicon. For evaluation, we used real-time PCR/HRM to test 25 unknown Pasteurellaceae isolates obtained from an external diagnostic laboratory and found the results to be consistent with those of partial 16S rRNA sequencing. The real-time PCR/HRM method provides a sensitive, rapid, and closed-tube approach for Pasteurellaceae species identification for health monitoring of laboratory mice. PMID- 26556282 TI - Bioelectrical impedance vector analysis in the critically ill: cool tool or just another 'toy'? AB - Assessment of volume and hydration status is far from easy and therefore technology such as bioelectrical impedance vector analysis (BIVA) may complement our examination techniques. This study highlights the fact that clinical assessment of volume balance and BIVA may correlate, but whether the routine use of BIVA will avoid significant volume overload in the critically ill remains unknown. Further studies are needed but at the moment appear a little way off. PMID- 26556283 TI - CO2 Chemistry of Phenolate-Based Ionic Liquids. AB - We synthesized ionic liquids (ILs) comprising an alkylphosphonium cation paired with phenolate, 4-nitrophenolate, and 4-methoxyphenolate anions that span a wide range of predicted reaction enthalpies with CO2. Each phenolate-based IL was characterized by spectroscopic techniques, and their physical properties (viscosity, conductivity, and CO2 solubility) were determined. We use the computational quantum chemical approach paired with experimental results to reveal the reaction mechanism of CO2 with phenolate ILs. Model chemistry shows that the oxygen atom of phenolate associates strongly with phosphonium cations and is able to deprotonate the cation to form an ylide with an affordable activation barrier. The ATR-FTIR and (31)P NMR spectra indicate that the phosphonium ylide formation and its reaction with CO2 are predominantly responsible for the observed CO2 uptake rather than direct anion-CO2 interaction. PMID- 26556284 TI - Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder. AB - Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation. PMID- 26556285 TI - Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder. AB - Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13 18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder. PMID- 26556286 TI - Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF. AB - Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors. PMID- 26556288 TI - Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy. AB - Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy. PMID- 26556290 TI - The Strategic Value of Succession Planning for Department Chairs. AB - Most faculty who aspire to be department chairs are unaware of succession processes at their institution. This Commentary highlights the importance of succession planning, emphasizing the general need for transparency. Succession planning provides institutional leaders the opportunity to optimize, renew, and revitalize their organization by ensuring successful leadership transitions. In contrast to leadership pathways in the military, corporate business, and hospital administration, planned succession of medical school department chairs has received little attention. Different approaches to succession planning are essential for emergency and planned transitions. Emergency succession plans should be in place at all times, regularly revisited, and modified as needed. Department chairs should begin considering their planned succession between one and five years after their initial appointment. The succession discussion between a chair and medical school dean requires cautious, thoughtful, and open discussions. Intradepartmental annual faculty performance evaluations permit the chair to mentor potential successors in acquiring future-oriented, institution based leadership qualities necessary to be considered for a future department chair position. If health and time permit, the successful chair should remain in his or her current position until a successor is named or, preferably, is in place. Appointment of an interim chair as part of succession planning can be useful for on-the-job training of an internal candidate, yet awkwardness might ensue if there is more than one internal candidate.Succession development offers the great advantage of maintaining smooth organizational performance while optimizing talent management and exploring opportunities for transitioning individuals into leadership roles. PMID- 26556289 TI - Defective Function of CD24(+)CD38(+) Regulatory B Cells in Ankylosing Spondylitis. AB - Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease strongly associated with HLA-B*27, an major histocompatibility complex (MHC) molecule that presents peptide antigen to T cells. Previously, regulatory B cells were found to suppress T cell-mediated autoimmunity induction and chronic inflammation, partially through interleukin (IL)-10 production. Here, we examined the role of regulatory B cells in AS pathogenesis. Apheresis samples from HLA-B*27-positive AS patients and non-AS healthy controls were collected. We found that although AS patients and non-AS controls presented similar frequencies of CD24(+)CD38(+) B cells, compared to non-AS controls, those from AS patients produced less IL-10 under ex vivo condition and after CD40 and B-cell receptor (BCR) stimulation. Purified T cell-B cell cocultures showed that compared to non-AS controls, CD24(+)CD38(+) B cells from AS patients were defective at suppressing naive and memory CD8(+) T cell activation. The suppression of memory CD8(+) T cells in non AS controls appeared to be mediated by IL-10, since the addition of IL-10 mAb suppressed CD24(+)CD38(+) B cell-mediated downregulation of proinflammatory cytokine production and proliferation. To rescue the defect in AS patients, CD24(+)CD38(+) B cells were pretreated by CD40 and BCR stimulation, which enhanced CD24(+)CD38(+) B cell-mediated memory CD8(+) T cell suppression. Together, our data discovered a regulatory B cell defect in AS patients. PMID- 26556291 TI - Evaluating the Productivity of VA, NIH, and AHRQ Health Services Research Career Development Awardees. AB - PURPOSE: To evaluate the academic advancement and productivity of Department of Veterans Affairs Health Services Research and Development (HSR&D) Career Development Award (CDA) program recipients, National Institutes of Health (NIH) K awardees in health services research (HSR), and Agency for Healthcare Research and Quality (AHRQ) K awardees. METHOD: In all, 219 HSR&D CDA recipients from fiscal year (FY) 1991 through FY2010; 154 NIH K01, K08, and K23 awardees FY1991 FY2010; and 69 AHRQ K01 and K08 awardees FY2000-FY2010 were included. Most data were obtained from curricula vitae. Academic advancement, publications, grants, recognition, and mentoring were compared after adjusting for years since award, and personal characteristics, training, and productivity prior to the award. RESULTS: No significant differences emerged in covariate-adjusted tenure-track academic rank, number of grants as primary investigator (PI), major journal articles as first/sole author, Hirsch h-index scores, likelihood of a journal editorship position or membership in a major granting review panel, or mentoring postgraduate researchers between the HSR&D CDA and NIH K awardees from FY1991 FY2010, or among the three groups of awardees from FY2000 or later. Among those who reported grant funding levels, HSR&D CDAs from FY1991-2010 had been PI on more grants of $100,000 than NIH K awardees. HSR&D CDAs had a higher mean number of major journal articles than NIH K awardees from FY1991-2010. CONCLUSIONS: Findings show that all three HSR career development programs are successfully selecting and mentoring awardees, ensuring additional HSR capacity to improve the quality and delivery of high-value care. PMID- 26556287 TI - Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder. AB - Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD. PMID- 26556292 TI - Needles and Haystacks: Finding Funding for Medical Education Research. AB - Medical education research suffers from a significant and persistent lack of funding. Although adequate funding has been shown to improve the quality of research, there are a number of factors that continue to limit it. The competitive environment for medical education research funding makes it essential to understand strategies for improving the search for funding sources and the preparation of proposals. This article offers a number of resources, strategies, and suggestions for finding funding. Investigators must be able to frame their research in the context of significant issues and principles in education. They must set their proposed work in the context of prior work and demonstrate its potential for significant new contributions. Because there are few funding sources earmarked for medical education research, researchers much also be creative, flexible, and adaptive as they seek to present their ideas in ways that are appealing and relevant to the goals of funders. Above all, the search for funding requires persistence and perseverance. PMID- 26556293 TI - Medical Students' Perception of Their Educational Environment and Quality of Life: Is There a Positive Association? AB - PURPOSE: To assess perceptions of educational environment of students from 22 Brazilian medical schools and to study the association between these perceptions and quality of life (QoL) measures. METHOD: The authors performed a multicenter study (August 2011 to August 2012), examining students' views both of (1) educational environment using the Dundee Ready Education Environment Measure (DREEM) and (2) QoL using the World Health Organization Quality of Life Assessment, abbreviated version (WHOQOL-BREF). They also examined students' self assessment of their overall QoL and medical-school-related QoL (MSQoL). The authors classified participants' perceptions into four quartiles according to DREEM total score, overall QoL, and MSQoL. RESULTS: Of 1,650 randomly selected students, 1,350 (81.8%) completed the study. The mean total DREEM score was 119.4 (standard deviation = 27.1). Higher total DREEM scores were associated with higher overall QoL and MSQoL scores (P < .001 for all comparisons) and younger ages (P < .001). Mean overall QoL scores were higher than MSQoL scores (mean difference, 1.35; 95% confidence interval [CI] 1.28-1.43; P < .001). Multinomial regression models showed significant dose-response patterns: Higher DREEM quartile scores were associated with better QoL. The psychological health domain of WHOQOL-BREF was most closely associated with DREEM scores (odds ratio 4.70; 95% CI = 3.80-5.81). CONCLUSIONS: The authors observed a positive association between QoL measures and DREEM scores. This association had a dose-response effect, independent of age, sex, and year of medical training, showing that educational environment appears to be an important moderator of medical student QoL. PMID- 26556294 TI - Increasing Resident Diversity in an Emergency Medicine Residency Program: A Pilot Intervention With Three Principal Strategies. AB - PROBLEM: Much work remains to be done to align the diversity of the health care workforce with the changing racial and ethnic backgrounds of patients, especially in the field of emergency medicine. APPROACH: In academic year (AY) 2012-2013, to increase the number of underrepresented minority (URM) candidates who were interviewed and matched, the Denver Health Residency in Emergency Medicine program (DHREM) initiated a focused pilot intervention with three principal strategies: (1) a scholarship-based externship program, (2) a funded second-look event, and (3) increased involvement and visibility of URM faculty in the interview and recruitment process. OUTCOMES: One year after implementation of the pilot intervention, the percentage of URMs among all applicants invited to interview at the DHREM doubled (7.1% [20/282] in AY 2011-2012, 7.0% [24/344] in AY 2012-2013, and 14.8% [58/393] in AY 2013-2014) (95% confidence interval [CI] = 5-10, 4-11, and 11-19, respectively). Of all DHREM interviewees in AY 2013-2014, 17.6% (49/279) (95% CI = 12-23) were URMs, nearly a threefold increase from AY 2012-2013 (6.2% [14/226], 95% CI = 3-10). In AY 2013-2014, 23.5% (4/17) (95% CI = 7-50) of all new DHREM residents were URMs, compared with 5.9% (1/17) in AY 2011 2012 and 5.6% (1/18) in AY 2012-2013 (95% CI = 0-29 and 0-27, respectively). NEXT STEPS: Additional studies are needed to determine whether these results are sustainable and generalizable to other residency programs in emergency medicine and other specialties. PMID- 26556295 TI - Developing Entrustable Professional Activities for Entry Into Clerkship. AB - PURPOSE: Despite the growing emphasis on early clinical experiences, preceptors still face challenges integrating preclerkship medical students into their practices. Entrustable professional activities (EPAs), which frame competencies in the context of clinical workplace activities, may provide explicit guidance on appropriate student roles and activities. This study aimed to develop and appraise content validity evidence for EPAs for clerkship entry. METHOD: The authors employed a multistep process from November 2012 to June 2014. They identified EPA content domains using study data, student focus groups, and preceptor interviews. They then mapped each domain to preclerkship course objectives, graduation competencies, and resident-level EPAs to ensure relevancy and adequacy. Next, they developed seven-part EPA descriptions for each domain with specifications/limitations; expected knowledge, skills, and attitudes; associated competencies; and assessment information. Subsequently, they conducted local, national, and international workshops to verify the appropriateness of the content and supervision level, before finalizing each EPA with additional expert and stakeholder review. RESULTS: This process resulted in five EPAs for entry into clerkship: (1) information gathering, (2) information integration for a differential diagnosis and plan, (3) health care team communication, (4) information sharing with patients, and (5) resource identification. Workshop participants approved and refined the content for each EPA and agreed that a single level of supervision (practice under reactive supervision) was appropriate. CONCLUSIONS: The development of these EPAs indicates support for setting a standard for entry into clerkship, provides guidance for engaging preclerkship students in clinical workplace activities, and can be adapted for use by any institution. PMID- 26556296 TI - Integrating Continuing Professional Development With Health System Reform: Building Pillars of Support. AB - Clinical failures sparked a widespread desire for health system reform at the beginning of the 21st century, but related efforts have resulted in changes that are either slow or nonexistent. In response, academic medicine has moved in two directions: (1) system-wide reform using electronic health records, practice networks, and widespread data applications (a macro pathway); and (2) professional development of individual clinicians through continuous performance improvement (a micro pathway). Both pathways exist to improve patient care and population health, yet each suffers from limitations in widespread implementation. The authors call for a better union between these two parallel pathways through four pillars of support: (1) an acknowledgment that both pathways are essential to each other and to the final outcome they intend to achieve, (2) a strong faculty commitment to educate about quality improvement and patient safety at all education levels, (3) a reengineering of tools for professional development to serve as effective change agents, and (4) the development of standards to sustain this alignment of pathways. With these pillars of support integrating continuing professional development with health system reform, the authors envision a better functioning system, with improved metrics and value to enhance patient care and population health. PMID- 26556297 TI - Using a Smartphone App and Coaching Group Sessions to Promote Residents' Reflection in the Workplace. AB - PROBLEM: Reflecting on workplace-based experiences is necessary for professional development. However, residents need support to raise their awareness of valuable moments for learning and to thoughtfully analyze those learning moments afterwards. APPROACH: From October to December 2012, the authors held a multidisciplinary six-week postgraduate training module focused on general competencies. Residents were randomly assigned to one of four conditions with varying degrees of reflection support; they were offered (1) a smartphone app, (2) coaching group sessions, (3) a combination of both, or (4) neither type of support. The app allowed participants to capture in real time learning moments as a text note, audio recording, picture, or video. Coaching sessions held every two weeks aimed to deepen participants' reflection on captured learning moments. Questionnaire responses and reflection data were compared between conditions to assess the effects of the app and coaching sessions on intensity and frequency of reflection. OUTCOMES: Sixty-four residents participated. App users reflected more often, captured more learning moments, and reported greater learning progress than nonapp users. Participants who attended coaching sessions were more alert to learning moments and pursued more follow-up learning activities to improve on the general competencies. Those who received both types of support were most alert to these learning moments. NEXT STEPS: A simple mobile app for capturing learning moments shows promise as a tool to support workplace-based learning, especially when combined with coaching sessions. Future research should evaluate these tools on a broader scale and in conjunction with residents' and students' personal digital portfolios. PMID- 26556298 TI - Perceptions of Peer-to-Peer Interprofessional Feedback Among Students in the Health Professions. AB - PURPOSE: Interprofessional teamwork should include interprofessional feedback to optimize performance and collaboration. Social identity theory predicts that hierarchy and stereotypes may limit receptiveness to interprofessional feedback, but literature on this is sparse. This study explores perceptions among health professions students regarding interprofessional peer feedback received after a team exercise. METHOD: In 2012-2013, students from seven health professions schools (medicine, pharmacy, nursing, dentistry, physical therapy, dietetics, and social work) participated in a team-based interprofessional exercise early in clinical training. Afterward, they wrote anonymous feedback comments for each other. Each student subsequently completed an online survey to rate the usefulness and positivity (on five-point scales) of feedback received and guessed each comment's source. Data analysis included analysis of variance to examine interactions (on usefulness and positivity ratings) between profession of feedback recipients and providers. RESULTS: Of 353 study participants, 242 (68.6%) accessed the feedback and 221 (62.6%) completed the survey. Overall, students perceived the feedback as useful (means across professions = 3.84-4.27) and positive (means = 4.17-4.86). There was no main effect of profession of the feedback provider, and no interactions between profession of recipient and profession of provider regardless of whether the actual or guessed provider profession was entered into the analysis. CONCLUSIONS: These findings suggest that students have positive perceptions of interprofessional feedback without systematic bias against any specific group. Whether students actually use interprofessional feedback for performance improvement and remain receptive toward such feedback as they progress in their professional education deserves further study. PMID- 26556299 TI - Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. AB - IMPORTANCE: Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. OBJECTIVE: To estimate the burden of germline variants identified through routine clinical tumor sequencing. DESIGN, SETTING, AND PARTICIPANTS: Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. MAIN OUTCOMES AND MEASURES: The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. RESULTS: The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99.9%; 95% CI, 99.6%-99.9%). CONCLUSIONS AND RELEVANCE: Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations. PMID- 26556300 TI - Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning. AB - Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning). PMID- 26556301 TI - Platelet response to a small molecule inhibitor of alpha2beta1 integrin is associated with ITGA2 C807T dimorphism. AB - High expression of the collagen receptor, alpha2beta1 integrin, on platelets of ITGA2 807T-allele carriers has been identified as a risk factor for thromboembolic conditions, and alpha2beta1 inhibitors are considered to be potential therapeutic agents. In 59 genotyped individuals, we measured alpha2 expression levels on platelets and analyzed platelet adhesion to collagen under flow conditions. A sulfonamide-type small-molecule inhibitor of alpha2beta1 integrin decreased average platelet adhesion in individuals with the C/T807T genotype but not in those harboring C807C. Thus, genotype can be used to select a human subpopulation that has the highest probability of showing a positive response to alpha2beta1 inhibitors. PMID- 26556303 TI - Quantitative monitoring of the removal of non-encapsulated material external to filled carbon nanotube samples. AB - The endohedral functionalization of carbon nanotubes with both organic and inorganic materials allows the development of tailored functional hybrids whose properties benefit from the synergistic effects of the constituent compounds. Bulk filling of carbon nanotubes (CNTs) results in samples that contain a large amount of non-encapsulated material external to the CNTs. The presence of the external material is detrimental to the processing and application of the resulting hybrids. Here we introduce the use of UV-Vis spectroscopy to monitor the cleaning process, i.e. the elimination of non-encapsulated compounds. Chrome azurol S has been employed to assess the bulk removal of external samarium(iii) chloride from filled single-walled carbon nanotubes. Chrome azurol S is of interest since it can be used to quantify a large variety of materials in a fast, accurate and reliable manner. The parameters that control the cleaning process have been optimized, including the time, temperature, volume and sonication, to achieve a fast and complete removal of the external material. PMID- 26556302 TI - Efficient Gene Transfer in Chick Retinas for Primary Cell Culture Studies: An Ex ovo Electroporation Approach. AB - The cone photoreceptor-enriched cultures derived from embryonic chick retinas have become an indispensable tool for researchers around the world studying the biology of retinal neurons, particularly photoreceptors. The applications of this system go beyond basic research, as they can easily be adapted to high throughput technologies for drug development. However, genetic manipulation of retinal photoreceptors in these cultures has proven to be very challenging, posing an important limitation to the usefulness of the system. We have recently developed and validated an ex ovo plasmid electroporation technique that increases the rate of transfection of retinal cells in these cultures by five-fold compared to other currently available protocols(1). In this method embryonic chick eyes are enucleated at stage 27, the RPE is removed, and the retinal cup is placed in a plasmid-containing solution and electroporated using easily constructed custom made electrodes. The retinas are then dissociated and cultured using standard procedures. This technique can be applied to overexpression studies as well as to the downregulation of gene expression, for example via the use of plasmid-driven RNAi technology, commonly achieving transgene expression in 25% of the photoreceptor population. The video format of the present publication will make this technology easily accessible to researchers in the field, enabling the study of gene function in primary retinal cultures. We have also included detailed explanations of the critical steps of this procedure for a successful outcome and reproducibility. PMID- 26556304 TI - Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance. AB - We recently showed that the mRNA expression of genes encoding for specific nutrient sensing receptors, namely the free fatty acid receptors (FFAR) 1, 2, 3, and the hydroxycarboxylic acid receptor (HCAR) 2, undergo characteristic changes during the transition from late pregnancy to lactation in certain adipose tissues (AT) of dairy cows. We hypothesised that divergent energy intake achieved by feeding diets with either high or low portions of concentrate (60% v. 30% concentrate on a dry matter basis) will alter the mRNA expression of FFAR 1, 2, 3, as well as HCAR2 in subcutaneous (SCAT) and retroperitoneal AT (RPAT) of dairy cows in the first 3 weeks postpartum (p.p.). For this purpose, 20 multiparous German Holstein cows were allocated to either the high concentrate ration (HC, n=10) or the low concentrate ration (LC, n=10) from day 1 to 21 p.p. Serum samples and biopsies of SCAT (tail head) and RPAT (above the peritoneum) were obtained at day -21, 1 and 21 relative to parturition. The mRNA abundances were measured by quantitative PCR. The concentrations of short-chain fatty acid (SCFA) in serum were measured by gas chromatography-flame ionisation detector. The FFAR1 and FFAR2 mRNA abundance in RPAT was higher at day -21 compared to day 1. At day 21 p.p. the FFAR2 mRNA abundance was 2.5-fold higher in RPAT of the LC animals compared to the HC cows. The FFAR3 mRNA abundance tended to lower values in SCAT of the LC group at day 21. The HCAR2 mRNA abundance was neither affected by time nor by feeding in both AT. On day 21 p.p. the HC group had 1.7-fold greater serum concentrations of propionic acid and lower concentrations of acetic acid (trend: 1.2-fold lower) compared with the LC group. Positive correlations between the mRNA abundance of HCAR2 and peroxisome proliferator-activated receptor gamma-2 (PPARG2) indicate a link between HCAR2 and PPARG2 in both AT. We observed an inverse regulation of FFAR2 and FFAR3 expression over time and both receptors also showed an inverse mRNA abundance as induced by different portions of concentrate. Thus, indicating divergent nutrient sensing of both receptors in AT during the transition period. We propose that the different manifestation of negative EB in both groups at day 21 after parturition affect at least FFAR2 expression in RPAT. PMID- 26556305 TI - A Nanobody Activation Immunotherapeutic that Selectively Destroys HER2-Positive Breast Cancer Cells. AB - We report a rationally designed nanobody activation immunotherapeutic that selectively redirects anti-dinitrophenyl (anti-DNP) antibodies to the surface of HER2-positive breast cancer cells, resulting in their targeted destruction by antibody-dependent cellular cytotoxicity. As nanobodies are relatively easy to express, stable, can be humanized, and can be evolved to potently and selectively bind virtually any disease-relevant cell surface receptor, we anticipate broad utility of this therapeutic strategy. PMID- 26556306 TI - In vitro testing of thiolated poly(aspartic acid) from ophthalmic formulation aspects. AB - Ocular drug delivery formulations must meet anatomical, biopharmaceutical, patient-driven and regulatory requirements. Mucoadhesive polymers can serve as a better alternative to currently available ophthalmic formulations by providing improved bioavailability. If all requirements are addressed, a polymeric formulation resembling the tear film of the eye might be the best solution. The optimum formulation must not have high osmotic activity, should provide appropriate surface tension, pH and refractive index, must be non-toxic and should be transparent and mucoadhesive. We would like to highlight the importance of in vitro polymer testing from a pharmaceutical aspect. We, therefore, carried out physical-chemical investigations to verify the suitability of certain systems for ophthalmic formulations. In this work, in situ gelling, mucoadhesive thiolated poly(aspartic acid)s were tested from ophthalmic formulation aspects. The results of preformulation measurements indicate that these polymers can be used as potential carriers in ophthalmic drug delivery. PMID- 26556307 TI - Speciation of americium in seawater and accumulation in the marine sponge Aplysina cavernicola. AB - The fate of radionuclides in the environment is a cause of great concern for modern society, seen especially in 2011 after the Fukushima accident. Among the environmental compartments, seawater covers most of the earth's surface and may be directly or indirectly impacted. The interaction between radionuclides and the marine compartment is therefore essential for better understanding the transfer mechanisms from the hydrosphere to the biosphere. This information allows for the evaluation of the impact on humans via our interaction with the biotope that has been largely undocumented up to now. In this report, we attempt to make a link between the speciation of heavy elements in natural seawater and their uptake by a model marine organism. More specifically, because the interaction of actinides with marine invertebrates has been poorly studied, the accumulation in a representative member of the Mediterranean coralligenous habitat, the sponge Aplysina cavernicola, was investigated and its uptake curve exposed to a radiotracer (241)Am was estimated using a high-purity Ge gamma spectrometer. But in order to go beyond the phenomenological accumulation rate, the speciation of americium(III) in seawater must be assessed. The speciation of (241)Am (and natural europium as its chemically stable surrogate) in seawater was determined using a combination of different techniques: Time-Resolved Laser-Induced Fluorescence (TRLIF), Extended X-ray Absorption Fine Structure (EXAFS) at the LIII edge, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy (SEM) and the resulting data were compared with the speciation modeling. In seawater, the americium(III) complex (as well as the corresponding europium complex, although with conformational differences) was identified as a ternary sodium biscarbonato complex, whose formula can be tentatively written as NaAm(CO3)2.nH2O. It is therefore this chemical form of americium that is accumulated by the sponge A. cavernicola. PMID- 26556308 TI - Migration and young people's mental health in Canada: A scoping review. AB - BACKGROUND: Young people's mental health is a public health priority. Given the influences of migration and resettlement on mental health, synthesis of current research with young people from migrant backgrounds can help inform mental health promotion initiatives that account for and are responsive to their needs. AIMS: This article distils the results of a review of published literature on the mental health of adolescent immigrants (ages 10-19) living in Canada. METHOD: Scoping review methods were used to define inclusion and exclusion criteria; inform the search strategies; and extract and synthesize key findings. RESULTS: Fourteen articles met criteria for inclusion. Analysis of the studies indicate diversity in mental health indicators, e.g., mental distress, emotional problems and behavioral problems, as well as a wide range of influences on mental health from age at migration and length of stay to place of residence, income and discrimination. CONCLUSIONS: Findings support the need to account for the array of influences on young people's mental health in relation to migration and to augment initiatives beyond the level of individual intervention. PMID- 26556310 TI - Characterization of genetic variation in TLR8 in relation to allergic rhinitis. AB - BACKGROUND: A previous investigation of all 10 TLR genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. This study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations. METHODS: The TLR8 gene was resequenced in 288 AR patients from Malmo and the data were compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared. RESULTS: Sequencing detected 13 polymorphisms (three promotor and 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF < 1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR association tests made using the BAMSE cohort yielded five P-values <0.05. Tests of IgE levels yielded four significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects, and response to different allergens in the different populations. CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveals contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. PMID- 26556311 TI - Phenylephrine preconditioning in embryonic heart H9c2 cells is mediated by up regulation of SUR2B/Kir6.2: A first evidence for functional role of SUR2B in sarcolemmal KATP channels and cardioprotection. AB - ATP-sensitive K(+) (KATP) channels were originally described in cardiomyocytes, where physiological levels of intracellular ATP keep them in a closed state. Structurally, these channels are composed of pore-forming inward rectifier, Kir6.1 or Kir6.2, and a regulatory, ATP-binding subunit, SUR1, SUR2A or SUR2B. SUR1 and Kir6.2 form pancreatic type of KATP channels, SUR2A and Kir6.2 form cardiac type of KATP channels, SUR2B and Kir6.1 form vascular smooth muscle type of KATP channels. The presence of SUR2B has been described in cardiomyocytes, but its functional significance and role has remained unknown. Pretreatment with phenylephrine (100nM) for 24h increased mRNA levels of SUR2B and Kir6.2, without affecting those levels of SUR1, SUR2A and Kir6.1 in embryonic heart H9c2 cells. Such increase was associated with increased K(+) current through KATP channels and Kir6.2/SUR2B protein complexes as revealed by whole cell patch clamp electrophysiology and immunoprecipitation/Western blotting respectively. Pretreatment with phenylephrine (100nM) generated a cellular phenotype that acquired resistance to chemical hypoxia induced by 2,4-dinitrophenol (DNP; 10mM), which was accompanied by increased in K(+) current in response to DNP (10mM). Cytoprotection afforded by phenylephrine (100nM) was abolished by infection of H9c2 cells with adenovirus containing Kir6.2AFA, a mutant form of Kir6.2 with largely reduced K(+) conductance. Taking all together, the present findings demonstrate that the activation of alpha1-adrenoceptors up-regulates SUR2B/Kir6.2 to confer cardioprotection. This is the first account of possible physiological role of SUR2B in cardiomyocytes. PMID- 26556312 TI - Intentional formation of a protein corona on nanoparticles: Serum concentration affects protein corona mass, surface charge, and nanoparticle-cell interaction. AB - The protein corona, which immediately is formed after contact of nanoparticles and biological systems, plays a crucial role for the biological fate of nanoparticles. In the here presented study we describe a strategy to control the amount of corona proteins which bind on particle surface and the impact of such a protein corona on particle-cell interactions. For corona formation, polyethyleneimine (PEI) coated magnetic nanoparticles (MNP) were incubated in a medium consisting of fetal calf serum (FCS) and cell culture medium. To modulate the amount of proteins bind to particles, the composition of the incubation medium was varied with regard to the FCS content. The protein corona mass was estimated and the size distribution of the participating proteins was determined by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, the zeta potential of incubated particles was measured. Human blood brain barrier-representing cell line HBMEC was used for in vitro incubation experiments. To investigate the consequences of the FCS dependent protein corona formation on the interaction of MNP and cells flow cytometry and laser scanning microscopy were used. Zeta potential as well as SDS-PAGE clearly reveal an increase in the amount of corona proteins on MNP with increasing amount of FCS in incubation medium. For MNP incubated with lower FCS concentrations especially medium-sized proteins of molecular weights between 30kDa and 100kDa could be found within the protein corona, whereas for MNP incubated within higher FCS concentrations the fraction of corona proteins of 30kDa and less increased. The presence of the protein corona reduces the interaction of PEI-coated MNP with HBMEC cells within a 30min-incubation. PMID- 26556313 TI - Spiro-oxindole derivative 5-chloro-4',5'-diphenyl-3'-(4-(2-(piperidin-1-yl) ethoxy) benzoyl) spiro[indoline-3,2'-pyrrolidin]-2-one triggers apoptosis in breast cancer cells via restoration of p53 function. AB - Breast cancer remains a significant health problem due to the involvement of multiple aberrant and redundant signaling pathways in tumorigenesis and the development of resistance to the existing therapeutic agents. Therefore, the search for novel chemotherapeutic agents for effective management of breast cancer is still warranted. In an effort to develop new anti-breast cancer agents, we have synthesized and identified novel spiro-oxindole derivative G613 i.e. 5 chloro-4',5'-diphenyl-3'-(4-(2-(piperidin-1-yl) ethoxy) benzoyl) spiro[indoline 3,2'-pyrrolidin]-2-one, which has shown growth inhibitory activity in breast cancer cells. The present study was aimed to explore the mechanism of anti tumorigenic action of this newly identified spiro-oxindole compound. Compound G613 inhibited the Mdm2-p53 interaction in breast cancer cells and tumor xenograft. It caused restoration of p53 function by activating its promoter activity, triggering its nuclear accumulation and preventing its ubiquitination and proteasomal degradation. Supportively, molecular docking studies revealed considerable homology in the docking mode of G613 and the known Mdm2 inhibitor Nutlin-3, to p53 binding pocket of Mdm2. The activation of p53 led to upregulation of p53 dependent pro-apoptotic proteins, Bax, Pumaalpha and Noxa and enhanced interaction of p53 with bcl2 member proteins thus triggering both transcription-dependent and transcription-independent apoptosis, respectively. Additionally, the compound decreased estrogen receptor activity through sequestration of estrogen receptor alpha by p53 thereby causing a decreased transcriptional activation and expression of proliferation markers. In conclusion, G613 represents a potent small-molecule inhibitor of the Mdm2-p53 interaction and can serve as a promising lead for developing a new class of anti cancer therapy for breast cancer patients. PMID- 26556314 TI - APC functions at the centrosome to stimulate microtubule growth. AB - The adenomatous polyposis coli (APC) tumor suppressor is multi-functional. APC is known to localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle. To test whether APC contributes to nascent microtubule (MT) growth at interphase centrosomes, we employed MT regrowth assays in U2OS cells to measure MT assembly before and after nocodazole treatment and release. We showed that siRNA knockdown of full-length APC delayed both initial MT aster formation and MT elongation/regrowth. In contrast, APC-mutant SW480 cancer cells displayed a defect in MT regrowth that was unaffected by APC knockdown, but which was rescued by reconstitution of full-length APC. Our findings identify APC as a positive regulator of centrosome MT initial assembly and suggest that this process is disrupted by cancer mutations. We confirmed that full-length APC associates with the MT-nucleation factor gamma-tubulin, and found that the APC cancer-truncated form (1-1309) also bound to gamma-tubulin through APC amino acids 1-453. While binding to gamma-tubulin may help target APC to the site of MT nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize MT growth. PMID- 26556316 TI - Synthesis, Hydrolysis, and Protonation-Promoted Intramolecular Reductive Breakdown of Potential NRTIs: Stavudine alpha-P-Borano-gamma-P-N-l tryptophanyltriphosphates. AB - Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of alpha-P-borano-gamma-P-substituted NTP analogs remains limited due to challenges with synthesis and purification. Here, we report the chemical synthesis and stability of a new potential class of NRTI prodrugs: stavudine (d4T) 5'-alpha-P-borano-gamma-P-N-L tryptophanyltriphosphates. One-pot synthesis of these compounds was achieved via a modified cyclic trimetaphosphate approach. Pure Rp and Sp diastereomers were obtained after HPLC separation. Based on LC-MS analysis, we report degradation pathways, half-lives (5-36 days) and mechanisms arising from structural differences to generate the corresponding borano tri- and di-phosphates, and H phosphonate, via several parallel routes in buffer at physiologically relevant pH and temperature. Here, the major hydrolysis products, d4T alpha-P boranotriphosphate Rp and Sp isomers, were isolated by HPLC and identified with spectral data. We first propose that one of the major degradation products, d4T H phosphonate, was generated from the d4T pronucleotides via a protonation-promoted intramolecular reduction followed by a second step nucleophilic attack. This report could provide valuable information for pronucleotide-based drug design in terms of selective release of target nucleotides. PMID- 26556315 TI - Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides. AB - Cladribine, 2-chloro-2'-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2'-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2 containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active. PMID- 26556319 TI - A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates-Bioinspired Sulfoxidation Catalysts. AB - A click chemistry approach based on the reaction between alkynylflavins and mono(6-azido-6-deoxy)-beta-cyclodextrin has proven to be a useful tool for the synthesis of flavin-cyclodextrin conjugates studied as monooxygenase mimics in enantioselective sulfoxidations. PMID- 26556317 TI - Purification and Partial Characterization of beta-Glucosidase in Chayote (Sechium edule). AB - beta-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this beta-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. beta-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other beta glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus beta glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of beta-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred MUg/mL beta-D-glucose inhibited beta-glucosidase activity by more than 50%. The enzyme had a Km of 4.88 mM with p-NPG and a Kcat of 10,000 min(-1). The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 degrees C. PMID- 26556321 TI - Polyphenolic Compositions and Chromatic Characteristics of Bog Bilberry Syrup Wines. AB - Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total anthocyanins and total phenols were around 15.12-16.23 mg/L and 475.82 to 486.50 mg GAE/L in fresh wines and declined 22%-31% and about 11% in bottle aged wines, respectively. In fresh wines, eight anthocyanins, six phenolic aids and 14 flavonols, but no flavon-3-ols were identified; Malvidin-3-O-glucoside, petunidin-3-O-glucoside and delphinium-3-O glucoside were the predominant pigments; Chlorogentic acid was the most abundant phenolic acid, and quercetin-3-O-galactoside and myricetin-3-O-galactoside accounted for nearly 90% of the total flavonols. During 6 months of bottle storage, the amounts of all the monomeric anthocyanins and phenolic acids were reduced dramatically, while the glycosidyl flavonols remained constant or were less reduced and their corresponding aglycones increased a lot. The effects of aging on blueberry wine color were described as the loss of color intensity with a dramatic change in color hue, from initial red-purple up to final red-brick nuances, while the pH of the fermentation matrix was negatively related to the color stability of aged wine. PMID- 26556320 TI - Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates. AB - Here we describe the synthesis and biological properties of two types of star shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA) based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5-5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates. PMID- 26556322 TI - Long-Term Lithium Treatment Increases cPLA2 and iPLA2 Activity in Cultured Cortical and Hippocampal Neurons. AB - BACKGROUND: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. OBJECTIVE: To investigate the effect of lithium on cytosolic phospholipase A2 (PLA2) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer's disease (AD). METHODS: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA2 and two PLA2 subtypes: cytosolic calcium-dependent (cPLA2); and calcium-independent (iPLA2). RESULTS: cPLA2 activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA2 activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. CONCLUSION: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA2. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA2 subtypes is tissue specific, i.e., iPLA2 in hippocampal neurons, and cPLA2 in cortical neurons. Because PLA2 activities are reported to be reduced in Alzheimer's disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease. PMID- 26556323 TI - Photostabilizing Efficiency of PVC in the Presence of Schiff Bases as Photostabilizers. AB - The photostabilization of polyvinyl chloride (PVC) films by Schiff bases was investigated. Polyvinyl chloride films containing 0.5 wt % Schiff bases were produced using the same casting method as that used for additive-free PVC films from tetrahydrofuran (THF) solvent. The photostabilization activities of these compounds were determined by monitoring the carbonyl, polyene and hydroxyl indices with irradiation time. The changes in viscosity average molecular weight of PVC with irradiation time were also monitored using THF as a solvent. The quantum yield of chain scission (Phics) for the studied complexes in PVC was estimated to range between 4.72 and 8.99 * 10(-8). According to the experimental results, several mechanisms were suggested, depending on the structure of the additive. Ultra violet (UV) absorption, peroxide decomposition and radical scavenging were suggested as the photostabilizing mechanisms. PMID- 26556324 TI - Hazardous Doping for Photo-Electrochemical Conversion: The Case of Nb-Doped Fe2O3 from First Principles. AB - The challenge of improving the efficiency of photo-electrochemical devices is often addressed through doping. However, this strategy could harm performance. Specifically, as demonstrated in a recent experiment, doping one of the most widely used materials for water splitting, iron (III) oxide (Fe2O3), with niobium (Nb) can still result in limited efficiency. In order to better understand the hazardous effect of doping, we use Density Functional Theory (DFT)+U for the case of Nb-doped Fe2O3. We find a direct correlation between the charge of the dopant, the charge on surface of the Fe2O3 material, and the overpotential required for water oxidation reaction. We believe that this work contributes to advancing our understanding of how to select effective dopants for materials. PMID- 26556325 TI - Radical Scavenging by Acetone: A New Perspective to Understand Laccase/ABTS Inactivation and to Recover Redox Mediator. AB - The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone on the kinetic constants of laccase were determined and the results showed Km and Vmax varied exponentially with increasing acetone content. Acetone as well as some other cosolvents could transform ABTS radicals into its reductive form. The content of acetone in media significantly affected the radical scavenging rates. Up to 95% of the oxidized ABTS was successfully recovered in 80% (v/v) acetone in 60 min. This allows ABTS recycles at least six times with 70%-75% of active radicals recovered after each cycle. This solvent-based recovery strategy may help improve the economic feasibility of laccase/ABTS system in biosynthesis. PMID- 26556326 TI - Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties. AB - A variety of novel 5-aryl thiophenes 4a-g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a-g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4 chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 +/- 0.11 at 15 ug/mL with IC50 17.1 ug/mL. Moreover, some other compounds 4a-f also exhibited very good inhibition against urease enzyme. PMID- 26556327 TI - Development and Characterization of Polymorphic Microsatellite Markers for Sedum sarmentosum (Crassulaceae) and Their Cross-Species Transferability. AB - Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic microsatellite markers were acquired with satisfactory amplifications and a polymorphic pattern in 48 S. sarmentosum individuals. The number of alleles ranged from 3 to 15. The observed and expected heterozygosities varied from 0.0833 to 0.8750 and 0.2168 to 0.9063, respectively. Two loci showed significant departure from the Hardy-Weinberg equilibrium. Cross-species amplification was carried out in other Sedum species. High rates of cross-species amplification were observed. The transferability value ranged from 85.7% in S. lineare to 64.3% in S. ellacombianum. These markers will be valuable for studying the genetic variation, population structure and germplasm characterization of S. sarmentosum and related Sedum species. PMID- 26556328 TI - Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization. AB - In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%-25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification. PMID- 26556329 TI - Phenolic Compounds from the Flowers of Bombax malabaricum and Their Antioxidant and Antiviral Activities. AB - Three new phenolic compounds 1-3 and twenty known ones 4-23 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of the isolated compounds were tested using FRAP and DPPH radical-scavenging assays, and compounds 4, 6, 8, 12, as well as the new compound 2, exhibited stronger antioxidant activities than ascorbic acid. Furthermore, all of compounds were tested for their antiviral activities against RSV by the CPE reduction assay and plaque reduction assay. Compounds 4, 10, 12 possess in vitro antiviral activities, and compound 10 exhibits potent anti-RSV effects, comparable to the positive control ribavirin. PMID- 26556330 TI - Water-Soluble Lignins from Different Bioenergy Crops Stimulate the Early Development of Maize (Zea mays, L.). AB - The molecular composition of water-soluble lignins isolated from four non-food bioenergy crops (cardoon CAR, eucalyptus EUC, and two black poplars RIP and LIM) was characterized in detail, and their potential bioactivity towards maize germination and early growth evaluated. Lignins were found to not affect seed germination rates, but stimulated the maize seedling development, though to a different extent. RIP promoted root elongation, while CAR only stimulated the length of lateral seminal roots and coleoptile, and LIM improved only the coleoptile development. The most significant bioactivity of CAR was related to its large content of aliphatic OH groups, C-O carbons and lowest hydrophobicity, as assessed by (31)P-NMR and (13)C-CPMAS-NMR spectroscopies. Less bioactive RIP and LIM lignins were similar in composition, but their stimulation of maize seedling was different. This was accounted to their diverse content of aliphatic OH groups and S- and G-type molecules. The poorest bioactivity of the EUC lignin was attributed to its smallest content of aliphatic OH groups and largest hydrophobicity. Both these features may be conducive of a EUC conformational structure tight enough to prevent its alteration by organic acids exuded from vegetal tissues. Conversely the more labile conformational arrangements of the other more hydrophilic lignin extracts promoted their bioactivity by releasing biologically active molecules upon the action of exuded organic acids. Our findings indicate that water-soluble lignins from non-food crops may be effectively used as plant biostimulants, thus contributing to increase the economic and ecological liability of bio-based industries. PMID- 26556331 TI - Immobilization of Cyclooxygenase-2 on Silica Gel Microspheres: Optimization and Characterization. AB - In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. Then, the mixture was shaken for 8 h at 20 degrees C. Results showed that the immobilized COX-2 produced by this method exhibited excellent biocatalytic activity, equivalent to that of free COX-2 under the test conditions employed. The best biocatalytic activity of immobilized COX-2 appeared at pH 8.0 and still maintained at about 84% (RSD < 7.39%, n = 3) at pH 10.0. For temperature tolerance, immobilized COX-2 exhibited its maximum biocatalytic activity at 40 degrees C and about 68% (RSD < 6.99%, n = 3) of the activity was maintained at 60 degrees C. The immobilized COX-2 retained over 85% (RSD < 7.26%, n = 3) of its initial biocatalytic activity after five cycles, and after 10 days storage, the catalytic activity of immobilized COX-2 still maintained at about 95% (RSD < 3.08%, n = 3). These characteristics ensured the convenient use of the immobilized COX-2 and reduced its production cost. PMID- 26556332 TI - Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution Phase Synthetic Approaches. AB - Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3 triazoloamide derivatives were developed. A secondary alpha-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; SN2 reaction with sodium azide; and the selective [3 + 2] Huisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively. PMID- 26556333 TI - Bitter Gentian Teas: Nutritional and Phytochemical Profiles, Polysaccharide Characterisation and Bioactivity. AB - As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally characterized with respect to their macronutrients, demonstrating the predominance of polysaccharides and low lipid content. Gentian decoctions were also submitted to a microcolumn RP-HPLC-UV analysis of phytochemicals demonstrating a high content of iridoids (177.18 641.04 MUg/mL) and flavonoids (89.15-405.71 MUg/mL). Additionally, mangiferin was detected in samples of G. triflora tea (19.89 MUg/mL). Five free sugars (fructose, glucose, sucrose, gentiobiose, gentianose) were identified in all gentian teas studied, as well as six organic acids (malic, citric, tartaric, oxalic, succinic, quinic). Pectic polysaccharides with a high content of rhamnogalacturonans and arabinogalactans were also identified and characterized in gentian decoctions for the first time. Gentian tea decoctions and their specific compounds (gentiopicroside, loganic acid-6'-O-beta-d-glucoside, isoorientin, isoorientin-4'-O-beta-d-glucoside, mangiferin, water-soluble polysaccharides) showed a promising antimicrobial, anti-inflammatory and antioxidant potentials. Evidences obtained indicate the prospective use of gentian herb teas as food products and medicines. PMID- 26556334 TI - Constituents and Pharmacological Activities of Myrcia (Myrtaceae): A Review of an Aromatic and Medicinal Group of Plants. AB - Myrcia is one of the largest genera of the economically important family Myrtaceae. Some of the species are used in folk medicine, such as a group known as "pedra-hume-caa" or "pedra-ume-caa" or "insulina vegetal" (insulin plant) that it is used for the treatment of diabetes. The species are an important source of essential oils, and most of the chemical studies on Myrcia describe the chemical composition of the essential oils, in which mono- and sesquiterpenes are predominant. The non-volatile compounds isolated from Myrcia are usually flavonoids, tannins, acetophenone derivatives and triterpenes. Anti-inflammatory, antinociceptive, antioxidant, antimicrobial activities have been described to Myrcia essential oils, while hypoglycemic, anti-hemorrhagic and antioxidant activities were attributed to the extracts. Flavonoid glucosides and acetophenone derivatives showed aldose reductase and alpha-glucosidase inhibition, and could explain the traditional use of Myrcia species to treat diabetes. Antimicrobial and anti-inflammatory are some of the activities observed for other isolated compounds from Myrcia. PMID- 26556336 TI - Gas-Phase Thermal Tautomerization of Imidazole-Acetic Acid: Theoretical and Computational Investigations. AB - The gas-phase thermal tautomerization reaction between imidazole-4-acetic (I) and imidazole-5-acetic (II) acids was monitored using the traditional hybrid functional (B3LYP) and the long-range corrected functionals (CAM-B3LYP and omegaB97XD) with 6-311++G** and aug-cc-pvdz basis sets. The roles of the long range and dispersion corrections on their geometrical parameters, thermodynamic functions, kinetics, dipole moments, Highest Occupied Molecular Orbital-Lowest Unoccupied Molecular Orbital (HOMO-LUMO) energy gaps and total hyperpolarizability were investigated. All tested levels of theory predicted the preference of I over II by 0.750-0.877 kcal/mol. The origin of predilection of I is assigned to the H-bonding interaction (nN8->sigma*O14-H15). This interaction stabilized I by 15.07 kcal/mol. The gas-phase interconversion between the two tautomers assumed a 1,2-proton shift mechanism, with two transition states (TS), TS1 and TS2, having energy barriers of 47.67-49.92 and 49.55-52.69 kcal/mol, respectively, and an sp3-type intermediate. A water-assisted 1,3-proton shift route brought the barrier height down to less than 20 kcal/mol in gas-phase and less than 12 kcal/mol in solution. The relatively high values of total hyperpolarizability of I compared to II were interpreted and discussed. PMID- 26556337 TI - Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement. AB - The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer-TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% +/- 0.69% and a loading capacity of 6.2% +/- 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 degrees C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity. PMID- 26556335 TI - Isolation and Culture of Pig Spermatogonial Stem Cells and Their in Vitro Differentiation into Neuron-Like Cells and Adipocytes. AB - Spermatogonial stem cells (SSCs) renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like cells and adipocytes. SSCs and Sertoli cells were isolated from neonatal piglet testis by differential adhesion and SSCs were cultured on a feeder layer of Sertoli cells. Third-generation SSCs were induced to differentiate into neuron-like cells by addition of retinoic acid, beta mercaptoethanol, and 3-isobutyl-1-methylxanthine (IBMX) to the induction media and into adipocytes by the addition of hexadecadrol, insulin, and IBMX to the induction media. The differentiated cells were characterized by biochemical staining, qRT-PCR, and immunocytochemistry. The cells were positive for SSC markers, including alkaline phosphatase and SSC-specific genes, consistent with the cells being undifferentiated. The isolated SSCs survived on the Sertoli cells for 15 generations. Karyotyping confirmed that the chromosomal number of the SSCs were normal for pig (2n = 38, n = 19). Pig SSCs were successfully induced into neuron-like cells eight days after induction and into adipocytes 22 days after induction as determined by biochemical and immunocytochemical staining. qPCR results also support this conclusion. The nervous tissue markers genes, Nestin and beta-tubulin, were expressed in the neuron-like cells and the adipocyte marker genes, PPARgamma and C/EBPalpha, were expressed in the adipocytes. PMID- 26556338 TI - Carbon Fluxes between Primary Metabolism and Phenolic Pathway in Plant Tissues under Stress. AB - Higher plants synthesize an amazing diversity of phenolic secondary metabolites. Phenolics are defined secondary metabolites or natural products because, originally, they were considered not essential for plant growth and development. Plant phenolics, like other natural compounds, provide the plant with specific adaptations to changing environmental conditions and, therefore, they are essential for plant defense mechanisms. Plant defensive traits are costly for plants due to the energy drain from growth toward defensive metabolite production. Being limited with environmental resources, plants have to decide how allocate these resources to various competing functions. This decision brings about trade-offs, i.e., promoting some functions by neglecting others as an inverse relationship. Many studies have been carried out in order to link an evaluation of plant performance (in terms of growth rate) with levels of defense related metabolites. Available results suggest that environmental stresses and stress-induced phenolics could be linked by a transduction pathway that involves: (i) the proline redox cycle; (ii) the stimulated oxidative pentose phosphate pathway; and, in turn, (iii) the reduced growth of plant tissues. PMID- 26556339 TI - Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis. AB - Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS) is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC) to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase IIIalpha (Topo IIIalpha), RMI1 (RecQ-mediated genome instability protein 1, BLAP75) and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), is crucial for maintaining genome stability. Recent work has demonstrated that RMI2 also plays critical role in SAC. However, little is know about RMI1 regulation during the cell cycle. Here we present that RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. Moreover, phosphorylation of RMI1 occurs in mitosis. Upon microtubule-disturbing agent, RMI1 is phosphorylated primarily at the sites of Serine 284 and Serine 292, which does not interfere with the formation of BTR complex. Additionally, this phosphorylation is partially reversed by roscovitine treatment, implying cycling dependent kinase 1 (CDK1) might be one of the upstream kinases. PMID- 26556340 TI - Roles of Sestrin2 and Ribosomal Protein S6 in Transient Global Ischemia-Induced Hippocampal Neuronal Injury. AB - Recent studies suggested that sestrin2 is a crucial modulator for the production of reactive oxygen species (ROS). In addition, sestrin2 may also regulate ribosomal protein S6 (RpS6), a molecule important for protein synthesis, through the effect of mammalian target of rapamycin (mTOR) complex that is pivotal for longevity. However, the roles of sestrin2 in cerebral ischemia, in which oxidative stress is one of the major pathogenic mechanisms, are still less understood. In this study, we hypothesized that sestrin2 may protect hippocampal CA1 neurons against transient global ischemia (TGI)-induced apoptosis by regulating RpS6 phosphorylation in rats. We found that sestrin2 expression was progressively increased in the hippocampal CA1 subfield 1-48 h after TGI, reaching the maximal level at 24 h, and declined thereafter. Further, an increased extent of RpS6 phosphorylation, but not total RpS6 protein level, was observed in the hippocampal CA1 subfield after TGI. The sestrin2 siRNA, which substantially blocked the expression of TGI-induced sestrin2, also abolished RpS6 phosphorylation. TGI with reperfusion may induce oxidative stress with the resultant formation of 8-hydroxy-deoxyguanosine (8-OHdG). We found that sestrin2 siRNA further augmented the formation of 8-OHdG induced by TGI with reperfusion for 4 h. Consistently, sestrin2 siRNA also enhanced apoptosis induced by TGI with reperfusion for 48 h based on the analysis of DNA fragmentation by agarose gel electrophoresis, DNA fragmentation sandwich ELISA, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Together these findings indicated that TGI-induced sestrin2 expression contributed to RpS6 phosphorylation and neuroprotection against ischemic injury in the hippocampal CA1 subfield. PMID- 26556342 TI - The Estrogen Receptor-beta Expression in De Quervain's Disease. AB - Stenosing tenosynovitis of the first dorsal compartment of the wrist (a.k.a. de Quervain's disease) is common but how estrogen is involved is still unknown. We previously reported that inflammation was involved in the pathogenesis of this ailment. In the present study, we extended our investigation of estrogen receptor (ER)-beta expression to determine whether estrogen is involved in the pathogenesis of de Quervain's. Intraoperative retinaculum samples were collected from 16 patients with the ailment. Specimens were histologically graded by collagen structure and immunohistochemically evaluated by quantifying the expression of ER-beta, interleukin (IL)-1beta and IL-6 (inflammatory cytokines), cyclooxygenase (COX)-2 (an inflammatory enzyme), and vascular endothelial growth factor (VEGF), and Von Willebrand's factor (vWF). De Quervain's occurs primarily in women. The female:male ratio in our study was 7:1. We found that ER-beta expression in the retinaculum was positively correlated with disease grade and patient age. Additionally, disease severity was associated with inflammatory factors--IL-1beta and IL-6, COX-2, and VEGF and vWF in tenosynovial tissue. The greater the levels of ER-beta expression, tissue inflammation, and angiogenesis are, the more severe de Quervain's disease is. ER-beta might be a useful target for novel de Quervain's disease therapy. PMID- 26556343 TI - Long Non-Coding RNAs in Endometrial Carcinoma. AB - Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed. PMID- 26556344 TI - Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment. AB - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD. PMID- 26556345 TI - CONSTITUTIVE PHOTOMORPHOGENIC 10 (COP10) Contributes to Floral Repression under Non-Inductive Short Days in Arabidopsis. AB - In Arabidopsis, CONSTITUTIVE PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA (COP/DET/FUS) genes act in repression of photomorphogenesis in darkness, and recent reports revealed that some of these genes, such as COP1 and DET1, also have important roles in controlling flowering time and circadian rhythm. The COP/DET/FUS protein COP10 interacts with DET1 and DNA DAMAGE-BINDING PROTEIN 1 (DDB1) to form a CDD complex and represses photomorphogenesis in darkness. The cop10-4 mutants flower normally in inductive long days (LD) but early in non-inductive short days (SD) compared with wild type (WT); however, the role of COP10 remains unknown. Here, we investigate the role of COP10 in SD-dependent floral repression. Reverse transcription-quantitative PCR revealed that in SD, expression of the LD dependent floral inducers GI, FKF1, and FT significantly increased in cop10-4 mutants, compared with WT. This suggests that COP10 mainly regulates FT expression in a CO-independent manner. We also show that COP10 interacts with GI in vitro and in vivo, suggesting that COP10 could also affect GI function at the posttranslational level. Moreover, FLC expression was repressed drastically in cop10-4 mutants and COP10 interacts with MULTICOPY SUPPRESSOR OF IRA1 4 (MSI4)/FVE (MSI4/FVE), which epigenetically inhibits FLC expression. These data suggest that COP10 contributes to delaying flowering in the photoperiod and autonomous pathways by downregulating FT expression under SD. PMID- 26556346 TI - Tissue Localization of Lymphocystis Disease Virus (LCDV) Receptor-27.8 kDa and Its Expression Kinetics Induced by the Viral Infection in Turbot (Scophthalmus maximus). AB - The 27.8 kDa membrane protein expressed in flounder (Paralichthys olivaceus) gill cells was proved to be a receptor mediating lymphocystis disease virus (LCDV) infection. In this study, SDS-PAGE and Western blotting demonstrated that 27.8 kDa receptor (27.8R) was shared by flounder and turbot (Scophthalmus maximus). Indirect immunofluorescence assay (IIFA) and immunohistochemistry showed that 27.8R was widely expressed in tested tissues of healthy turbot. The indirect enzyme-linked immunosorbent assay indicated that 27.8R expression was relatively higher in stomach, gill, heart, and intestine, followed by skin, head kidney, spleen, blood cells, kidney and liver, and lower in ovary and brain in healthy turbot, and it was significantly up-regulated after LCDV infection. Meanwhile, real-time quantitative PCR demonstrated that LCDV was detected in heart, peripheral blood cells, and head kidney at 3 h post infection (p.i.), and then in other tested tissues at 12 h p.i. LCDV copies increased in a time-dependent manner, and were generally higher in the tissues with higher 27.8R expression. Additionally, IIFA showed that 27.8R and LCDV were detected at 3 h p.i. in some leukocytes. These results suggested that 27.8R also served as a receptor in turbot, and LCDV can infect some leukocytes which might result in LCDV spreading to different tissues in turbot. PMID- 26556347 TI - Molecular Characterization of Endoplasmic Reticulum Oxidoreductin 1 from Bombyx mori. AB - We isolated a complementary DNA (cDNA) clone encoding endoplasmic reticulum oxidoreductin 1 (bERO1, a specific oxidant of protein disulfide isomerase (PDI)) from Bombyx mori. This protein has a putative open reading frame (ORF) of 489 amino acids and a predicted size of 57.4 kDa. Although bERO1 protein shares less than 57% amino acid sequence homology with other reported ERO1s, it contains two conserved redox active motifs, a Cys-X-X-X-X-Cys motif of N-terminal and Cys-X-X Cys-X-X-Cys motif of C-terminal. Both motifs are typically present in ERO1 protein family members. The bEro1 mRNA expression was highest in posterior silk gland on the sixth day of the 5th instar larvae. Expression of bEro1 mRNA also markedly increased during endoplasmic reticulum (ER) stress induced by stimulation with antimycin, calcium ionophore A23187, dithiothreitol, H2O2, monencin, and tunicamycin. In addition, expression levels of bEro1 exactly coincided with that of bPdi. This is the first result suggesting that bERO1 plays an essential role in ER quality control through the combined activities of bERO1 and bPDI as a catalyst of protein folding in the ER and sustaining cellular redox homeostasis. PMID- 26556341 TI - Alzheimer's Disease: Mechanism and Approach to Cell Therapy. AB - Alzheimer's disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells. PMID- 26556348 TI - Validation of PDE9A Gene Identified in GWAS Showing Strong Association with Milk Production Traits in Chinese Holstein. AB - Phosphodiesterase9A (PDE9A) is a cyclic guanosine monophosphate (cGMP)-specific enzyme widely expressed among the tissues, which is important in activating cGMP dependent signaling pathways. In our previous genome-wide association study, a single nucleotide polymorphism (SNP) (BTA-55340-no-rs(b)) located in the intron 14 of PDE9A, was found to be significantly associated with protein yield. In addition, we found that PDE9A was highly expressed in mammary gland by analyzing its mRNA expression in different tissues. The objectives of this study were to identify genetic polymorphisms of PDE9A and to determine the effects of these variants on milk production traits in dairy cattle. DNA sequencing identified 11 single nucleotide polymorphisms (SNPs) and six SNPs in 5' regulatory region were genotyped to test for the subsequent association analyses. After Bonferroni correction for multiple testing, all these identified SNPs were statistically significant for one or more milk production traits (p < 0.0001~0.0077). Interestingly, haplotype-based association analysis revealed similar effects on milk production traits (p < 0.01). In follow-up RNA expression analyses, two SNPs (c.-1376 G>A, c.-724 A>G) were involved in the regulation of gene expression. Consequently, our findings provide confirmatory evidences for associations of PDE9A variants with milk production traits and these identified SNPs may serve as genetic markers to accelerate Chinese Holstein breeding program. PMID- 26556349 TI - Posterior Wnts Have Distinct Roles in Specification and Patterning of the Planarian Posterior Region. AB - The wnt signaling pathway is an intercellular communication mechanism essential in cell-fate specification, tissue patterning and regional-identity specification. A betacatenin-dependent signal specifies the AP (Anteroposterior) axis of planarians, both during regeneration of new tissues and during normal homeostasis. Accordingly, four wnts (posterior wnts) are expressed in a nested manner in central and posterior regions of planarians. We have analyzed the specific role of each posterior wnt and the possible cooperation between them in specifying and patterning planarian central and posterior regions. We show that each posterior wnt exerts a distinct role during re-specification and maintenance of the central and posterior planarian regions, and that the integration of the different wnt signals (betacatenin dependent and independent) underlies the patterning of the AP axis from the central region to the tip of the tail. Based on these findings and data from the literature, we propose a model for patterning the planarian AP axis. PMID- 26556353 TI - A New Analytic Alignment Method for a SINS. AB - Analytic alignment is a type of self-alignment for a Strapdown inertial navigation system (SINS) that is based solely on two non-collinear vectors, which are the gravity and rotational velocity vectors of the Earth at a stationary base on the ground. The attitude of the SINS with respect to the Earth can be obtained directly using the TRIAD algorithm given two vector measurements. For a traditional analytic coarse alignment, all six outputs from the inertial measurement unit (IMU) are used to compute the attitude. In this study, a novel analytic alignment method called selective alignment is presented. This method uses only three outputs of the IMU and a few properties from the remaining outputs such as the sign and the approximate value to calculate the attitude. Simulations and experimental results demonstrate the validity of this method, and the precision of yaw is improved using the selective alignment method compared to the traditional analytic coarse alignment method in the vehicle experiment. The selective alignment principle provides an accurate relationship between the outputs and the attitude of the SINS relative to the Earth for a stationary base, and it is an extension of the TRIAD algorithm. The selective alignment approach has potential uses in applications such as self-alignment, fault detection, and self-calibration. PMID- 26556352 TI - Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-kappaB Activation, and IkappaBalpha Degradation. AB - Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-kappaB and IkappaBalpha degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis. PMID- 26556351 TI - Endoplasmic Reticulum Stress Signaling in Plant Immunity--At the Crossroad of Life and Death. AB - Rapid and complex immune responses are induced in plants upon pathogen recognition. One form of plant defense response is a programmed burst in transcription and translation of pathogenesis-related proteins, of which many rely on ER processing. Interestingly, several ER stress marker genes are up regulated during early stages of immune responses, suggesting that enhanced ER capacity is needed for immunity. Eukaryotic cells respond to ER stress through conserved signaling networks initiated by specific ER stress sensors tethered to the ER membrane. Depending on the nature of ER stress the cell prioritizes either survival or initiates programmed cell death (PCD). At present two plant ER stress sensors, bZIP28 and IRE1, have been described. Both sensor proteins are involved in ER stress-induced signaling, but only IRE1 has been additionally linked to immunity. A second branch of immune responses relies on PCD. In mammals, ER stress sensors are involved in activation of PCD, but it is unclear if plant ER stress sensors play a role in PCD. Nevertheless, some ER resident proteins have been linked to pathogen-induced cell death in plants. In this review, we will discuss the current understanding of plant ER stress signaling and its cross-talk with immune signaling. PMID- 26556350 TI - Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts. AB - DNA alkylating drugs have been used in clinics for more than seventy years. The diversity of their mechanism of action (major/minor groove; mono-/bis-alkylation; intra-/inter-strand crosslinks; DNA stabilization/destabilization, etc.) has undoubtedly major consequences on the cellular response to treatment. The aim of this review is to highlight the variety of established protein recognition of DNA adducts to then particularly focus on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) function in DNA adduct interaction with illustration using original experiments performed with S23906-1/DNA adduct. The introduction of this review is a state of the art of protein/DNA adducts recognition, depending on the major or minor groove orientation of the DNA bonding as well as on the molecular consequences in terms of double-stranded DNA maintenance. It reviews the implication of proteins from both DNA repair, transcription, replication and chromatin maintenance in selective DNA adduct recognition. The main section of the manuscript is focusing on the implication of the moonlighting protein GAPDH in DNA adduct recognition with the model of the peculiar DNA minor groove alkylating and destabilizing drug S23906-1. The mechanism of action of S23906-1 alkylating drug and the large variety of GAPDH cellular functions are presented prior to focus on GAPDH direct binding to S23906-1 adducts. PMID- 26556354 TI - Centrifugal Microfluidic System for Nucleic Acid Amplification and Detection. AB - We report here the development of a rapid PCR microfluidic system comprising a double-shaft turntable and centrifugal-based disc that rapidly drives the PCR mixture between chambers set at different temperatures, and the bidirectional flow improved the space utilization of the disc. Three heating resistors and thermistors maintained uniform, specific temperatures for the denaturation, annealing, and extension steps of the PCR. Infrared imaging showed that there was little thermal interference between reaction chambers; the system enabled the cycle number and reaction time of each step to be independently adjusted. To validate the function and efficiency of the centrifugal microfluidic system, a 350-base pair target gene from the hepatitis B virus was amplified and quantitated by fluorescence detection. By optimizing the cycling parameters, the reaction time was reduced to 32 min as compared to 120 min for a commercial PCR machine. DNA samples with concentrations ranging from 10 to 106 copies/mL could be quantitatively analyzed using this system. This centrifugal-based microfluidic platform is a useful system and possesses industrialization potential that can be used for portable diagnostics. PMID- 26556355 TI - Automated Identification of River Hydromorphological Features Using UAV High Resolution Aerial Imagery. AB - European legislation is driving the development of methods for river ecosystem protection in light of concerns over water quality and ecology. Key to their success is the accurate and rapid characterisation of physical features (i.e., hydromorphology) along the river. Image pattern recognition techniques have been successfully used for this purpose. The reliability of the methodology depends on both the quality of the aerial imagery and the pattern recognition technique used. Recent studies have proved the potential of Unmanned Aerial Vehicles (UAVs) to increase the quality of the imagery by capturing high resolution photography. Similarly, Artificial Neural Networks (ANN) have been shown to be a high precision tool for automated recognition of environmental patterns. This paper presents a UAV based framework for the identification of hydromorphological features from high resolution RGB aerial imagery using a novel classification technique based on ANNs. The framework is developed for a 1.4 km river reach along the river Dee in Wales, United Kingdom. For this purpose, a Falcon 8 octocopter was used to gather 2.5 cm resolution imagery. The results show that the accuracy of the framework is above 81%, performing particularly well at recognising vegetation. These results leverage the use of UAVs for environmental policy implementation and demonstrate the potential of ANNs and RGB imagery for high precision river monitoring and river management. PMID- 26556356 TI - An Open Source Low-Cost Wireless Control System for a Forced Circulation Solar Plant. AB - The article describes the design phase, development and practical application of a low-cost control system for a forced circulation solar plant in an outdoor test cell located near Milan. Such a system provides for the use of an electric pump for the circulation of heat transfer fluid connecting the solar thermal panel to the storage tank. The running plant temperatures are the fundamental parameter to evaluate the system performance such as proper operation, and the control and management system has to consider these parameters. A solar energy-powered wireless-based smart object was developed, able to monitor the running temperatures of a solar thermal system and aimed at moving beyond standard monitoring approaches to achieve a low-cost and customizable device, even in terms of installation in different environmental conditions. To this end, two types of communications were used: the first is a low-cost communication based on the ZigBee protocol used for control purposes, so that it can be customized according to specific needs, while the second is based on a Bluetooth protocol used for data display. PMID- 26556357 TI - A Hybrid Lifetime Extended Directional Approach for WBANs. AB - Wireless Body Area Networks (WBANs) can provide real-time and reliable health monitoring, attributing to the human-centered and sensor interoperability properties. WBANs have become a key component of the ubiquitous eHealth (electronic health) revolution that prospers on the basis of information and communication technologies. The prime consideration in WBAN is how to maximize the network lifetime with battery-powered sensor nodes in energy constraint. Novel solutions in Medium Access Control (MAC) protocols are imperative to satisfy the particular BAN scenario and the need of excellent energy efficiency in healthcare applications. In this paper, we propose a hybrid Lifetime Extended Directional Approach (LEDA) MAC protocol based on IEEE 802.15.6 to reduce energy consumption and prolong network lifetime. The LEDA MAC protocol takes full advantages of directional superiority in energy saving that employs multi-beam directional mode in Carrier Sense Multiple Access/Collision Avoidance (CSMA/CA) and single-beam directional mode in Time Division Multiple Access (TDMA) for alternative in data reservation and transmission according to the traffic varieties. Moreover, the impacts of some inherent problems of directional antennas such as deafness and hidden terminal problem can be decreased owing to that all nodes generate individual beam according to user priorities designated. Furthermore, LEDA MAC employs a Dynamic Polled Allocation Period (DPAP) for burst data transmissions to increase the network reliability and adaptability. Extensive analysis and simulation results show that the proposed LEDA MAC protocol achieves extended network lifetime with improved performance compared with IEEE 802.15.6. PMID- 26556358 TI - State Tracking and Fault Diagnosis for Dynamic Systems Using Labeled Uncertainty Graph. AB - Cyber-physical systems such as autonomous spacecraft, power plants and automotive systems become more vulnerable to unanticipated failures as their complexity increases. Accurate tracking of system dynamics and fault diagnosis are essential. This paper presents an efficient state estimation method for dynamic systems modeled as concurrent probabilistic automata. First, the Labeled Uncertainty Graph (LUG) method in the planning domain is introduced to describe the state tracking and fault diagnosis processes. Because the system model is probabilistic, the Monte Carlo technique is employed to sample the probability distribution of belief states. In addition, to address the sample impoverishment problem, an innovative look-ahead technique is proposed to recursively generate most likely belief states without exhaustively checking all possible successor modes. The overall algorithms incorporate two major steps: a roll-forward process that estimates system state and identifies faults, and a roll-backward process that analyzes possible system trajectories once the faults have been detected. We demonstrate the effectiveness of this approach by applying it to a real world domain: the power supply control unit of a spacecraft. PMID- 26556359 TI - A Hybrid Sender- and Receiver-Initiated Protocol Scheme in Underwater Acoustic Sensor Networks. AB - In this paper, we propose a method for sharing the handshakes of control packets among multiple nodes, which we call a hybrid sender- and receiver-initiated (HSR) protocol scheme. Handshake-sharing can be achieved by inviting neighbors to join the current handshake and by allowing them to send their data packets without requiring extra handshakes. Thus, HSR can reduce the signaling overhead involved in control packet exchanges during handshakes, as well as resolve the spatial unfairness problem between nodes. From an operational perspective, HSR resembles the well-known handshake-sharing scheme referred to as the medium access control (MAC) protocol using reverse opportunistic packet appending (ROPA). However, in ROPA the waiting time is not controllable for the receiver's neighbors and thus unexpected collisions may occur at the receiver due to hidden neighbors, whereas the proposed scheme allows all nodes to avoid hidden-node-induced collisions according to an elaborately calculated waiting time. Our computer simulations demonstrated that HSR outperforms ROPA with respect to both the throughput and delay by around 9.65% and 11.36%, respectively. PMID- 26556360 TI - 3D Analysis of HCMV Induced-Nuclear Membrane Structures by FIB/SEM Tomography: Insight into an Unprecedented Membrane Morphology. AB - We show that focused ion beam/scanning electron microscopy (FIB/SEM) tomography is an excellent method to analyze the three-dimensional structure of a fibroblast nucleus infected with human cytomegalovirus (HCMV). We found that the previously described infoldings of the inner nuclear membrane, which are unique among its kind, form an extremely complex network of membrane structures not predictable by previous two-dimensional studies. In all cases they contained further invaginations (2nd and 3rd order infoldings). Quantification revealed 5498HCMV capsids within two nuclear segments, allowing an estimate of 15,000 to 30,000 capsids in the entire nucleus five days post infection. Only 0.8% proved to be enveloped capsids which were exclusively detected in 1st order infoldings (perinuclear space). Distribution of the capsids between 1st, 2nd and 3rd order infoldings is in complete agreement with the envelopment/de-envelopment model for egress of HCMV capsids from the nucleus and we confirm that capsid budding does occur at the large infoldings. Based on our results we propose the pushing membrane model: HCMV infection induces local disruption of the nuclear lamina and synthesis of new membrane material which is pushed into the nucleoplasm, forming complex membrane infoldings in a highly abundant manner, which then may be also used by nucleocapsids for budding. PMID- 26556361 TI - The Impact of Wolbachia on Virus Infection in Mosquitoes. AB - Mosquito-borne viruses such as dengue, West Nile and chikungunya viruses cause significant morbidity and mortality in human populations. Since current methods are not sufficient to control disease occurrence, novel methods to control transmission of arboviruses would be beneficial. Recent studies have shown that virus infection and transmission in insects can be impeded by co-infection with the bacterium Wolbachia pipientis. Wolbachia is a maternally inherited endosymbiont that is commonly found in insects, including a number of mosquito vector species. In Drosophila, Wolbachia mediates antiviral protection against a broad range of RNA viruses. This discovery pointed to a potential strategy to interfere with mosquito transmission of arboviruses by artificially infecting mosquitoes with Wolbachia. This review outlines research on the prevalence of Wolbachia in mosquito vector species and the impact of antiviral effects in both naturally and artificially Wolbachia-infected mosquitoes. PMID- 26556362 TI - Composite Sequence-Structure Stability Models as Screening Tools for Identifying Vulnerable Targets for HIV Drug and Vaccine Development. AB - Rapid evolution and high sequence diversity enable Human Immunodeficiency Virus (HIV) populations to acquire mutations to escape antiretroviral drugs and host immune responses, and thus are major obstacles for the control of the pandemic. One strategy to overcome this problem is to focus drugs and vaccines on regions of the viral genome in which mutations are likely to cripple function through destabilization of viral proteins. Studies relying on sequence conservation alone have had only limited success in determining critically important regions. We tested the ability of two structure-based computational models to assign sites in the HIV-1 capsid protein (CA) that would be refractory to mutational change. The destabilizing mutations predicted by these models were rarely found in a database of 5811 HIV-1 CA coding sequences, with none being present at a frequency greater than 2%. Furthermore, 90% of variants with the low predicted stability (from a set of 184 CA variants whose replication fitness or infectivity has been studied in vitro) had aberrant capsid structures and reduced viral infectivity. Based on the predicted stability, we identified 45 CA sites prone to destabilizing mutations. More than half of these sites are targets of one or more known CA inhibitors. The CA regions enriched with these sites also overlap with peptides shown to induce cellular immune responses associated with lower viral loads in infected individuals. Lastly, a joint scoring metric that takes into account both sequence conservation and protein structure stability performed better at identifying deleterious mutations than sequence conservation or structure stability information alone. The computational sequence-structure stability approach proposed here might therefore be useful for identifying immutable sites in a protein for experimental validation as potential targets for drug and vaccine development. PMID- 26556363 TI - Human T-Lymphotropic Virus Type I (HTLV-1) Infection among Iranian Blood Donors: First Case-Control Study on the Risk Factors. AB - Human T-cell lymphotropic virus type 1 (HTLV-1) infection is an endemic condition in Northeast Iran and, as such, identification of risk factors associated with the infection in this region seems to be a necessity. All the possible risk factors for HTLV-1 seropositivity among first-time blood donors were evaluated in Mashhad, Iran, during the period of 2011-2012. Blood donation volunteers were interviewed for demographic data, medical history, and behavioral characteristics and the frequencies of risk factors were compared between HTLV-1 positive (case) and HTLV-1 negative (control) donors. The data was analyzed using Chi square and t-tests. Logistic regression analysis was performed to identify independent risk factors for the infection. Assessments were carried out on 246 cases aged 17-60 and 776 controls aged 17-59, who were matched based on their ages, gender, and date and center of donation. Logistic analysis showed low income (OR = 1.53, p = 0.035), low educational level (OR = 1.64, p = 0.049), being born in the cities of either Mashhad (OR = 2.47, p = 0.001) or Neyshabour (OR = 4.30, p < 0001), and a history of blood transfusion (OR = 3.17, p = 0.007) or non-IV drug abuse (OR = 3.77, p < 0.0001) were significant predictors for infection with HTLV-1. Lack of variability or small sample size could be reasons of failure to detect some well known risk factors for HTLV-1 infection, such as prolonged breastfeeding and sexual promiscuity. Pre-donation screening of possible risk factors for transfusion-transmissible infections should also be considered as an important issue, however, a revision of the screening criteria such as a history of transfusion for more than one year prior to donation is strongly recommended. PMID- 26556364 TI - Microneedle Coating Techniques for Transdermal Drug Delivery. AB - Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID- 26556365 TI - Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers. AB - Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 +/- 0.19 years; BMI z score 2.67 +/- 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 +/- 0.23 years; BMI z-score 0.03 +/- 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers. PMID- 26556366 TI - The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food. AB - Ovotransferrin or conalbumin belong to the transferrin protein family and is endowed with both iron-transfer and protective activities. In addition to its well-known antibacterial properties, ovotransferrin displays other protective roles similar to those already ascertained for the homologous mammalian lactoferrin. These additional functions, in many cases not directly related to iron binding, are also displayed by the peptides derived from partial hydrolysis of ovotransferrin, suggesting a direct relationship between egg consumption and human health. PMID- 26556367 TI - Mediterranean Alcohol-Drinking Pattern and the Incidence of Cardiovascular Disease and Cardiovascular Mortality: The SUN Project. AB - BACKGROUND: We assessed the still unclear effect of the overall alcohol-drinking pattern, beyond the amount of alcohol consumed, on the incidence of cardiovascular clinical disease (CVD). METHODS: We followed 14,651 participants during up to 14 years. We built a score assessing simultaneously seven dimensions of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, preference for wine, red wine consumption, wine consumed during meals and avoidance of binge drinking. RESULTS: During 142,177 person-years of follow-up, 127 incident cases of CVD (myocardial infarction, stroke or cardiovascular mortality) were identified. Compared with the category of better conformity with the MADP, the low-adherence group exhibited a non-significantly higher risk (HR) of total CVD ((95% CI) = 1.55 (0.58-4.16)). This direct association with a departure from the traditional MADP was even stronger for cardiovascular mortality (HR (95% CI) = 3.35 (0.77-14.5)). Nevertheless, all these associations were statistically non significant. CONCLUSION: Better conformity with the MADP seemed to be associated with lower cardiovascular risk in most point estimates; however, no significant results were found and more powered studies are needed to clarify the role of the MADP on CVD. PMID- 26556368 TI - Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. AB - Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long term. Isocaloric diets containing 16%-23% fat and 57%-65% carbohydrate lower liver fat compared to diets with 43%-55% fat and 27%-38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance. PMID- 26556369 TI - Definition of the Mediterranean Diet; a Literature Review. AB - Numerous studies over several decades suggest that following the Mediterranean diet (MedDiet) can reduce the risk of cardiovascular disease and cancer, and improve cognitive health. However, there are inconsistencies among methods used for evaluating and defining the MedDiet. Through a review of the literature, we aimed to quantitatively define the MedDiet by food groups and nutrients. Databases PubMed, MEDLINE, Science Direct, Academic Search Premier and the University of South Australia Library Catalogue were searched. Articles were included if they defined the MedDiet in at least two of the following ways: (1) general descriptive definitions; (2) diet pyramids/numbers of servings of key foods; (3) grams of key foods/food groups; and (4) nutrient and flavonoid content. Quantity of key foods and nutrient content was recorded and the mean was calculated. The MedDiet contained three to nine serves of vegetables, half to two serves of fruit, one to 13 serves of cereals and up to eight serves of olive oil daily. It contained approximately 9300 kJ, 37% as total fat, 18% as monounsaturated and 9% as saturated, and 33 g of fibre per day. Our results provide a defined nutrient content and range of servings for the MedDiet based on past and current literature. More detailed reporting amongst studies could refine the definition further. PMID- 26556370 TI - Better Adherence to the Mediterranean Diet Could Mitigate the Adverse Consequences of Obesity on Cardiovascular Disease: The SUN Prospective Cohort. AB - Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or >=6 points in the Trichopoulou's Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93 2.25) for >=25 - <30 kg/m2 of BMI and 2.00 (1.04-3.83) for >=30 kg/m2 of BMI, compared to a BMI < 25 kg/m2. In contrast, these estimates were 0.77 (0.35-1.67) and 1.15 (0.39-3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity. PMID- 26556372 TI - A rapid and sensitive method to measure the functional activity of Shiga toxins in human serum. AB - Shiga toxins (Stx) have a definite role in the development of hemolytic uremic syndrome in children with hemorrhagic colitis caused by pathogenic Stx-producing Escherichia coli (STEC) strains. The dramatic effects of these toxins on the microvasculature of different organs, particularly of the kidney, are well known, whereas there is no consensus on the mechanism by which Stx reach the endothelia of target organs and/or indirectly injure these body sites. We hereby describe a quick (4 h), radioactive, Raji cell-based method designed for the detection of Stx in human sera. The assay monitors the translation impairment induced by these powerful inhibitors of protein synthesis, which are identified properly by neutralizing their activity with specific monoclonal antibodies. By this method, we detected for the first time the functional activity of Stx in sera of STEC infected patients during hemorrhagic colitis. Recent research has pointed to a dynamic process of Stx-induced renal intoxication in which concurrent and interactive steps are involved. Our rapid and specific method could be useful for studying the kinetics of Stx during the natural course of STEC infection and the interplay between Stx activity in serum and Stx presence in different blood fractions (neutrophils, monocytes, platelets, leukocyte-platelet aggregates, microvesicles, lipoproteins). PMID- 26556373 TI - Variation in type A trichothecene production and trichothecene biosynthetic genes in Fusarium goolgardi from natural ecosystems of Australia. AB - Fusarium goolgardi, isolated from the grass tree Xanthorrhoea glauca in natural ecosystems of Australia, is closely related to fusaria that produce a subgroup of trichothecene (type A) mycotoxins that lack a carbonyl group at carbon atom 8 (C 8). Mass spectrometric analysis revealed that F. goolgardi isolates produce type A trichothecenes, but exhibited one of two chemotypes. Some isolates (50%) produced multiple type A trichothecenes, including 4,15-diacetoxyscirpenol (DAS), neosolaniol (NEO), 8-acetylneosolaniol (Ac-NEO) and T-2 toxin (DAS-NEO-T2 chemotype). Other isolates (50%) produced only DAS (DAS chemotype). In the phylogenies inferred from DNA sequences of genes encoding the RNA polymerase II largest (RPB1) and second largest (RPB2) subunits as well as the trichothecene biosynthetic genes (TRI), F. goolgardi isolates were resolved as a monophyletic clade, distinct from other type A trichothecene-producing species. However, the relationships of F. goolgardi to the other species varied depending on whether phylogenies were inferred from RPB1 and RPB2, the 12-gene TRI cluster, the two gene TRI1-TRI16 locus, or the single-gene TRI101 locus. Phylogenies based on different TRI loci resolved isolates with different chemotypes into distinct clades, even though only the TRI1-TRI16 locus is responsible for structural variation at C-8. Sequence analysis indicated that TRI1 and TRI16 are functional in F. goolgardi isolates with the DAS-NEO-T2 chemotype, but non-functional in isolates with DAS chemotype due to the presence of premature stop codons caused by a point mutation. PMID- 26556374 TI - Mycotoxigenic fungi and natural co-occurrence of mycotoxins in rainbow trout (Oncorhynchus mykiss) feeds. AB - Samples of rainbow trout feed were analyzed with the aim to determine the mycobiota composition and the co-occurrence of mycotoxins. A total of 28 samples of finished rainbow trout feed from hatcheries in the provinces of Rio Negro and Neuquen, Argentina, were studied. Fungal counts were obtained on three culture media in the ranges of <10 to 4.2 * 104 CFU/g on Dichloran Rose Bengal Chloramphenicol Agar (DRBC), <10 to 5.1 * 104 CFU/g on Dichloran Chloramphenicol Peptone Agar (DCPA) and <10 to 3.6 * 104 CFU/g on Dichloran 18% Glycerol Agar (DG18). The most frequent mycotoxigenic fungi were Eurotium (frequency (Fr) 25.0%), followed by Penicillium (Fr 21.4%) and Aspergillus (Fr 3.6%). The most prevalent mycotoxigenic species were E. repens (Fr 21.4%) and E. rubrum (Fr 14.3%). All samples were contaminated with mycotoxins: 64% samples were contaminated with T-2 toxin (median 70.08 ppb), 50% samples with zearalenone (median 87.97 ppb) and aflatoxins (median 2.82 ppb), 25% with ochratoxin A (median 5.26 ppb) and 3.57% samples with deoxynivalenol (median 230 ppb). Eight samples had a fumonisins contamination level below the limit of detection. Co occurrence of six mycotoxins was determined in 7% of the samples. PMID- 26556375 TI - Cell-to-cell propagation of the bacterial toxin CNF1 via extracellular vesicles: potential impact on the therapeutic use of the toxin. AB - Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-kappaB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity. PMID- 26556371 TI - Current status and future directions of botulinum neurotoxins for targeting pain processing. AB - Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics. PMID- 26556376 TI - Studies on the bioavailability of deoxynivalenol (DON) and DON sulfonate (DONS) 1, 2, and 3 in pigs fed with sodium sulfite-treated DON-contaminated maize. AB - Deoxynivalenol (DON) exposure of pigs might cause serious problems when critical dietary toxin concentrations are exceeded. As DON contamination of agricultural crops cannot be completely prevented, detoxification measures are needed. Wet preservation with sodium sulfite resulted in a significant DON reduction of naturally-contaminated maize in previous experiments. The preserved material had a characteristic DON sulfonates (DONS) pattern. DONS is known to be less toxic than DON but its stability was shown to depend on pH, which gives rise to the question if a back-conversion to DON occurs in vivo. Therefore, the toxicokinetics and bioavailability of DON and DONS were studied in pigs. After the administration of a single oral or intravenous bolus of DON or DONS, serial blood samples were collected and subsequently analyzed. DONS was not detectable after oral administration of DONS mixtures. The results showed further that the bioavailability of DONS as DON in pigs fed maize preserved wet with sodium sulfite was significantly decreased compared to untreated control maize (DON), indicating that DONS obviously did not convert back to DON to a large extent in vivo. Moreover, the fact that DONS was not detectable in systemic blood requires further investigations regarding their ingestive and/or metabolic fate. PMID- 26556377 TI - Topography of Slow Sigma Power during Sleep is Associated with Processing Speed in Preschool Children. AB - Cognitive development is influenced by maturational changes in processing speed, a construct reflecting the rapidity of executing cognitive operations. Although cognitive ability and processing speed are linked to spindles and sigma power in the sleep electroencephalogram (EEG), little is known about such associations in early childhood, a time of major neuronal refinement. We calculated EEG power for slow (10-13 Hz) and fast (13.25-17 Hz) sigma power from all-night high-density electroencephalography (EEG) in a cross-sectional sample of healthy preschool children (n = 10, 4.3 +/- 1.0 years). Processing speed was assessed as simple reaction time. On average, reaction time was 1409 +/- 251 ms; slow sigma power was 4.0 +/- 1.5 MUV2; and fast sigma power was 0.9 +/- 0.2 MUV2. Both slow and fast sigma power predominated over central areas. Only slow sigma power was correlated with processing speed in a large parietal electrode cluster (p < 0.05, r ranging from -0.6 to -0.8), such that greater power predicted faster reaction time. Our findings indicate regional correlates between sigma power and processing speed that are specific to early childhood and provide novel insights into the neurobiological features of the EEG that may underlie developing cognitive abilities. PMID- 26556378 TI - From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology. AB - In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1beta. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge), which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status. PMID- 26556379 TI - Challenges in Commercializing Biomimetic Membranes. AB - The discovery of selective water channel proteins-aquaporins-has prompted growing interest in using these proteins, as the building blocks for designing new types of membranes. However, as with any other new and potentially disruptive technology, barriers for successful market entry exist. One category includes customer-related barriers, which can be influenced to some extent. Another category includes market-technical-related barriers, which can be very difficult to overcome by an organization/company aiming at successfully introducing their innovation on the market-in particular if both the organization and the technology are at early stages. Often, one faces barriers from both these categories at the same time, which makes it necessary to gain insight of the particular market when introducing a new innovative product. In this review we present the basic concepts and discuss some of these barriers and challenges associated with introducing biomimetic aquaporin membranes. These include technical issues in membrane production and product testing. Then we discuss possible business models for introducing new technologies in general, followed by a presentation of beach-head market segments relevant for biomimetic aquaporin membranes. PMID- 26556380 TI - Fabrication of Poly-l-lactic Acid/Dicalcium Phosphate Dihydrate Composite Scaffolds with High Mechanical Strength-Implications for Bone Tissue Engineering. AB - Scaffolds were fabricated from poly-l-lactic acid (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting. Sodium citrate and PLLA were used to improve the mechanical properties of the DCPD scaffolds. The resulting PLLA/DCPD composite scaffold had increased diametral tensile strength and fracture energy when compared to DCPD only scaffolds (1.05 vs. 2.70 MPa and 2.53 vs. 12.67 N-mm, respectively). Sodium citrate alone accelerated the degradation rate by 1.5 times independent of PLLA. Cytocompatibility of all samples were evaluated using proliferation and differentiation parameters of dog-bone marrow stromal cells (dog-BMSCs). The results showed that viable dog-BMSCs attached well on both DCPD and PLLA/DCPD composite surfaces. In both DCPD and PLLA/DCPD conditioned medium, dog-BMSCs proliferated well and expressed alkaline phosphatase (ALP) activity indicating cell differentiation. These findings indicate that incorporating both sodium citrate and PLLA could effectively improve mechanical strength and biocompatibility without increasing the degradation time of calcium phosphate cement scaffolds for bone tissue engineering purposes. PMID- 26556382 TI - Smart micelle@polydopamine core-shell nanoparticles for highly effective chemo photothermal combination therapy. AB - In this investigation, we have designed and synthesized a novel core-shell polymer nanoparticle system for highly effective chemo-photothermal combination therapy. A nanoscale DSPE-PEG micelle encapsulating doxorubicin (Dox-M) was designed as a core, and then modified by a polydopamine (PDA) shell for photothermal therapy and bortezomib (Btz) administration (Dox-M@PDA-Btz). The facile conjugation of Btz to the catechol-containing PDA shell can form a reversible pH-sensitive boronic acid-catechol conjugate to create a stimuli responsive drug carrier system. As expected, the micelle@PDA core-shell nanoparticles exhibited satisfactory photothermal efficiency, which has potential for thermal ablation of malignant tissues. In addition, on account of the PDA modification, both Dox and Btz release processes were pH-dependent and NIR dependent. Both in vitro and in vivo studies illustrated that the Dox-M@PDA-Btz nanoparticles coupled with laser irradiation could enhance the cytotoxicity, and thus combinational therapy efficacy was achieved when integrating Dox, Btz, and PDA into a single nanoplatform. Altogether, our current study indicated that the micelle@polydopamine core-shell nanoparticles could be applied for NIR/pH responsive sustained-release and synergized chemo-photothermal therapy for breast cancer. PMID- 26556383 TI - Realtime analysis and visualization of MinION sequencing data with npReader. AB - MOTIVATION: The recently released Oxford Nanopore MinION sequencing platform presents many innovative features opening up potential for a range of applications not previously possible. Among these features, the ability to sequence in real-time provides a unique opportunity for many time-critical applications. While many software packages have been developed to analyze its data, there is still a lack of toolkits that support the streaming and real-time analysis of MinION sequencing data. RESULTS: We developed npReader, an open source software package to facilitate real-time analysis of MinION sequencing data. npReader can simultaneously extract sequence reads and stream them to downstream analysis pipelines while the samples are being sequenced on the MinION device. It provides a command line interface for easy integration into a bioinformatics work flow, as well as a graphical user interface which concurrently displays the statistics of the run. It also provides an application programming interface for development of streaming algorithms in order to fully utilize the extent of nanopore sequencing potential. AVAILABILITY AND IMPLEMENTATION: npReader is written in Java and is freely available at https://github.com/mdcao/npReader CONTACT: m.cao1@uq.edu.au or l.coin@imb.uq.edu.au. PMID- 26556384 TI - Flexible data integration and curation using a graph-based approach. AB - MOTIVATION: The increasing diversity of data available to the biomedical scientist holds promise for better understanding of diseases and discovery of new treatments for patients. In order to provide a complete picture of a biomedical question, data from many different origins needs to be combined into a unified representation. During this data integration process, inevitable errors and ambiguities present in the initial sources compromise the quality of the resulting data warehouse, and greatly diminish the scientific value of the content. Expensive and time-consuming manual curation is then required to improve the quality of the information. However, it becomes increasingly difficult to dedicate and optimize the resources for data integration projects as available repositories are growing both in size and in number everyday. RESULTS: We present a new generic methodology to identify problematic records, causing what we describe as 'data hairball' structures. The approach is graph-based and relies on two metrics traditionally used in social sciences: the graph density and the betweenness centrality. We evaluate and discuss these measures and show their relevance for flexible, optimized and automated data curation and linkage. The methodology focuses on information coherence and correctness to improve the scientific meaningfulness of data integration endeavors, such as knowledge bases and large data warehouses. CONTACT: samuel.croset@roche.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26556381 TI - Alcohol, Aldehydes, Adducts and Airways. AB - Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4 hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA) adduct and hybrid malondialdehyde acetaldehyde (MAA) protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease. PMID- 26556385 TI - Specific identification and quantification of circular RNAs from sequencing data. AB - MOTIVATION: Circular RNAs (circRNAs) are a poorly characterized class of molecules that have been identified decades ago. Emerging high-throughput sequencing methods as well as first reports on confirmed functions have sparked new interest in this RNA species. However, the computational detection and quantification tools are still limited. RESULTS: We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. DCC applies a series of filters and integrates data across replicate sets to arrive at a precise list of circRNA candidates. We assessed the detection performance of DCC on a newly generated mouse brain data set and publicly available sequencing data. Our software achieves a much higher precision than state-of-the-art competitors at similar sensitivity levels. Moreover, DCC estimates circRNA versus host gene expression from counting junction and non junction reads. These read counts are finally used to test for host gene independence of circRNA expression across different experimental conditions by our R package CircTest We demonstrate the benefits of this approach on previously reported age-dependent circRNAs in the fruit fly. AVAILABILITY AND IMPLEMENTATION: The source code of DCC and CircTest is licensed under the GNU General Public Licence (GPL) version 3 and available from https://github.com/dieterich-lab/[DCC or CircTest]. CONTACT: christoph.dieterich@age.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26556386 TI - contamDE: differential expression analysis of RNA-seq data for contaminated tumor samples. AB - MOTIVATION: Accurate detection of differentially expressed genes between tumor and normal samples is a primary approach of cancer-related biomarker identification. Due to the infiltration of tumor surrounding normal cells, the expression data derived from tumor samples would always be contaminated with normal cells. Ignoring such cellular contamination would deflate the power of detecting DE genes and further confound the biological interpretation of the analysis results. For the time being, there does not exists any differential expression analysis approach for RNA-seq data in literature that can properly account for the contamination of tumor samples. RESULTS: Without appealing to any extra information, we develop a new method 'contamDE' based on a novel statistical model that associates RNA-seq expression levels with cell types. It is demonstrated through simulation studies that contamDE could be much more powerful than the existing methods that ignore the contamination. In the application to two cancer studies, contamDE uniquely found several potential therapy and prognostic biomarkers of prostate cancer and non-small cell lung cancer. AVAILABILITY AND IMPLEMENTATION: An R package contamDE is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/ CONTACT: zhanghfd@fudan.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26556388 TI - SpectralTDF: transition densities of diffusion processes with time-varying selection parameters, mutation rates and effective population sizes. AB - MOTIVATION: In the Wright-Fisher diffusion, the transition density function describes the time evolution of the population-wide frequency of an allele. This function has several practical applications in population genetics and computing it for biologically realistic scenarios with selection and demography is an important problem. RESULTS: We develop an efficient method for finding a spectral representation of the transition density function for a general model where the effective population size, selection coefficients and mutation parameters vary over time in a piecewise constant manner. AVAILABILITY AND IMPLEMENTATION: The method, called SpectralTDF, is available at https://sourceforge.net/projects/spectraltdf/ CONTACT: yss@berkeley.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26556387 TI - BioNetFit: a fitting tool compatible with BioNetGen, NFsim and distributed computing environments. AB - Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here, we present BioNetFit, a general-purpose fitting tool that is compatible with BioNetGen and NFsim. BioNetFit is designed to take advantage of distributed computing resources. This feature facilitates fitting (i.e. optimization of parameter values for consistency with data) when simulations are computationally expensive. AVAILABILITY AND IMPLEMENTATION: BioNetFit can be used on stand-alone Mac, Windows/Cygwin, and Linux platforms and on Linux-based clusters running SLURM, Torque/PBS, or SGE. The BioNetFit source code (Perl) is freely available (http://bionetfit.nau.edu). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: bionetgen.help@gmail.com. PMID- 26556389 TI - The effects of tDCS upon sustained visual attention are dependent on cognitive load. AB - Transcranial Direct Current Stimulation (tDCS) modulates the excitability of neuronal responses and consequently can affect performance on a variety of cognitive tasks. However, the interaction between cognitive load and the effects of tDCS is currently not well-understood. We recorded the performance accuracy of participants on a bilateral multiple object tracking task while undergoing bilateral stimulation assumed to enhance (anodal) and decrease (cathodal) neuronal excitability. Stimulation was applied to the posterior parietal cortex (PPC), a region inferred to be at the centre of an attentional tracking network that shows load-dependent activation. 34 participants underwent three separate stimulation conditions across three days. Each subject received (1) left cathodal / right anodal PPC tDCS, (2) left anodal / right cathodal PPC tDCS, and (3) sham tDCS. The number of targets-to-be-tracked was also manipulated, giving a low (one target per visual field), medium (two targets per visual field) or high (three targets per visual field) tracking load condition. It was found that tracking performance at high attentional loads was significantly reduced in both stimulation conditions relative to sham, and this was apparent in both visual fields, regardless of the direction of polarity upon the brain's hemispheres. We interpret this as an interaction between cognitive load and tDCS, and suggest that tDCS may degrade attentional performance when cognitive networks become overtaxed and unable to compensate as a result. Systematically varying cognitive load may therefore be a fruitful direction to elucidate the effects of tDCS upon cognitive functions. PMID- 26556390 TI - Validity and Reliability of the Dutch Version of the International Hip Outcome Tool (iHOT-12NL) in Patients With Disorders of the Hip. AB - STUDY DESIGN: Clinical measurement. OBJECTIVES: To translate and culturally adapt the international Hip Outcome Tool (iHOT-12) into Dutch and to determine its validity and reliability. BACKGROUND: The iHOT-12 for measuring health-related quality of life and physical functioning in younger, active patients with hip pathology is available in English and Swedish. The tool is scored on a 0-to-100 point scale, with higher scores reflecting better function. A Dutch version of the questionnaire, with demonstrated high validity and reliability, is needed for both clinical and research purposes. METHODS: The iHOT-12 was translated and culturally adapted from English into Dutch (iHOT-12NL). Subsequently, the iHOT 12NL, RAND 36-Item Health Survey, Hip disability and Osteoarthritis Outcome Score (HOOS), and Tegner activity scale were completed by 117 patients with hip pathologies. Structural validity was analyzed using exploratory principal component factor analysis. To determine construct validity, 12 hypotheses were predefined regarding relationships between the iHOT-12NL and subscales of the RAND 36-Item Health Survey, Hip disability and Osteoarthritis Outcome Score, and Tegner activity scale. To determine test-retest reliability, 61 patients completed the iHOT-12NL on a second occasion within a 2-week period. Intraclass correlation coefficient (ICC), Cronbach alpha, standard error of measurement (SEM), and minimal detectable change (MDC) were calculated to assess reliability. Bland-Altman analysis was conducted to assess bias between test and retest. RESULTS: Factor analysis revealed that the iHOT-12NL has 1 component. Construct validity was good, as 83% of the hypotheses were confirmed. Internal consistency was good, with a Cronbach alpha of .96. The ICC was 0.93 (95% confidence interval: 0.88, 0.96), demonstrating good test-retest reliability. The SEM was 7.3 points. Individual- and group-level MDC values were 20.2 and 2.6 points, respectively. Bland-Altman analysis showed an absence of bias. CONCLUSION: The iHOT-12NL is a reliable and valid instrument for measuring physical functioning and health-related quality of life in younger, physically active patients with hip pathology. PMID- 26556391 TI - The Effect of Knee Braces on Quadriceps Strength and Inhibition in Subjects With Patellofemoral Osteoarthritis. AB - STUDY DESIGN: Secondary analysis of a randomized controlled trial. BACKGROUND: The use of external supports has been questioned because they may lead to weakness in the surrounding muscles. To our knowledge, there is no investigation into the effect of knee supports or braces on quadriceps muscle strength and quadriceps inhibition in individuals with patellofemoral joint (PFJ) osteoarthritis (OA). OBJECTIVES: To investigate the effects of a flexible knee support on quadriceps maximum voluntary contraction (MVC) and arthrogenous muscle inhibition (AMI) in patients with PFJ OA. METHODS: The study included 108 participants who had at least 3 months of patellofemoral pain and a Kellgren Lawrence score of 2 or 3 for PFJ OA. The participants were randomized to a group that wore a flexible knee support (brace) or a group that did not wear a support (no brace) in a 6-week randomized controlled trial, followed by an open-label trial, in which all participants wore the brace for a total of 12 weeks. Quadriceps MVC, measured isometrically, and quadriceps AMI, measured by twitch interpolation, were assessed at the 6-week and 12-week time points. RESULTS: After 6 weeks, MVC did not differ between the brace and no-brace groups (9.09 Nm; 95% confidence interval [CI]: -4.89, 23.07; P = .20). Arthrogenous muscle inhibition significantly decreased in the brace group (-8.62%; 95% CI: -13.90%, 3.33%; P = .002). After 12 weeks, in all of the participants who wore a flexible knee support, MVC increased by 7.98 Nm (95% CI: 2.52, 13.45; P = .004) and AMI decreased (-8.42%; 95% CI: -11.48%, -5.36%; P<.001). Although statistically significant, these results have doubtful clinical significance. CONCLUSION: A patellofemoral flexible knee support in participants with PFJ OA does not have an adverse effect on quadriceps MVC or AMI. Using a knee support should not be discouraged because of concerns about deleterious effects on quadriceps strength and inhibition. LEVEL OF EVIDENCE: Therapy, level 1b. PMID- 26556392 TI - Orthopaedic Physical Therapy: Update to the Description of Specialty Practice. AB - STUDY DESIGN: Descriptive, cross-sectional observational study. BACKGROUND: In the physical therapist profession, the outcomes of specialty practice analyses are used to determine content areas for specialty board examinations and for American Physical Therapy Association (APTA)-accredited residency curricula. To maintain currency for specialty practices, the American Board of Physical Therapy Specialties (ABPTS) requires any approved specialty area to revalidate its Description of Specialty Practice (DSP) a minimum of every 10 years. OBJECTIVES: The purpose of this article was to describe the most recent practice analysis process and to report revisions to the DSP for orthopaedic physical therapists. METHODS: A survey instrument was developed by a group of subject matter experts, following guidelines established by the ABPTS. The survey was sent electronically to a random sample of 800 orthopaedic certified specialists (OCSs). The survey contained 5 sections: (1) knowledge areas (eg, human anatomy and physiology); (2) professional roles, responsibilities, and values (eg, consultation); (3) patient/client management model (eg, examination); (4) percentage of body regions treated; and (5) demographic information. RESULTS: A total of 224 completed surveys and 43 partially completed surveys were submitted, for a response rate of 33.4%. Based on a priori decision rules regarding survey data, consensus of the group of subject matter experts, and ABPTS suggestions, the DSP for orthopaedic physical therapy was revised. CONCLUSION: The revised DSP will be used to reconstruct the blueprint for future OCS examinations, APTA-accredited orthopaedic residency program curricula, as well as professional development activities related to recertification in orthopaedic physical therapy. PMID- 26556393 TI - Electrically Elicited Muscle Torque: Comparison Between 2500-Hz Burst-Modulated Alternating Current and Monophasic Pulsed Current. AB - STUDY DESIGN: Single-blind, block-randomization crossover design. OBJECTIVE: To compare the knee extensor muscle torque production elicited with 2500-Hz burst modulated alternating current (BMAC) and with a monophasic pulsed current (MPC) at the maximum tolerated stimulation intensity. BACKGROUND: Neuromuscular electrical stimulation (NMES) is often used for strengthening the quadriceps following knee surgery. Strength gains are dependent on muscle torque production, which is primarily limited by discomfort. Burst-modulated alternating current stimulation is a clinically popular waveform for NMES. Prior research has established that MPC with a relatively long pulse duration is effective for high muscle torque production. METHODS: Participants in this study were 20 adults with no history of knee injury. A crossover design was used to randomize the order in which each participant's dominant or nondominant lower extremity received NMES and the waveform (MPC or BMAC) this limb received. Stimulation intensity was incrementally increased until participants reached their maximum tolerance. The torque produced was converted to a percentage of each participant's maximum volitional isometric contraction of the respective limb. RESULTS: A general linear model for a 2-treatment, 2-period crossover design was utilized to analyze the results. The mean +/- SD electrically induced percent maximum volitional isometric contraction at maximal participant tolerance was 49.5% +/- 19.6% for MPC and 29.8% +/- 12.4% for BMAC. This difference was statistically significant (P = .002) after accounting for treatment order and limb, which had no effect on torque production. CONCLUSION: Neuromuscular stimulation using MPC may be more efficacious than using BMAC to achieve a high torque output in patients with quadriceps weakness. PMID- 26556394 TI - The human cathelicidin LL-37--A pore-forming antibacterial peptide and host-cell modulator. AB - The human cathelicidin hCAP18/LL-37 has become a paradigm for the pleiotropic roles of peptides in host defence. It has a remarkably wide functional repertoire that includes direct antimicrobial activities against various types of microorganisms, the role of 'alarmin' that helps to orchestrate the immune response to infection, the capacity to locally modulate inflammation both enhancing it to aid in combating infection and limiting it to prevent damage to infected tissues, the promotion of angiogenesis and wound healing, and possibly also the elimination of abnormal cells. LL-37 manages to carry out all its reported activities with a small and simple, amphipathic, helical structure. In this review we consider how different aspects of its primary and secondary structures, as well as its marked tendency to form oligomers under physiological solution conditions and then bind to molecular surfaces as such, explain some of its cytotoxic and immunomodulatory effects. We consider its modes of interaction with bacterial membranes and capacity to act as a pore-forming toxin directed by our organism against bacterial cells, contrasting this with the mode of action of related peptides from other species. We also consider its different membrane dependent effects on our own cells, which underlie many of its other activities in host defence. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. PMID- 26556396 TI - Wellness-related Use of Common Complementary Health Approaches Among Adults: United States, 2012. AB - OBJECTIVE: This report presents national estimates of selected wellness-related reasons for the use of natural product supplements, yoga, and spinal manipulation among U.S. adults in 2012. Self-reported perceived health outcomes were also examined. METHODS: Data from 34,252 adults aged 18 and over collected as part of the 2012 National Health Interview Survey were analyzed for this report. In particular, whether adults who used selected complementary health approaches did so to treat a specific health condition or for any of five wellness-related reasons was examined, as well as whether these adults perceived that this use led to any of nine health-related outcomes. Sampling weights were used to produce national estimates that are representative of the civilian noninstitutionalized U.S. adults population. RESULTS: Users of natural product supplements and yoga were more likely to have reported using the approach for a wellness reason than for treatment of a specific health condition, whereas more spinal manipulation users reported using it for treatment rather than for wellness. The most common wellness-related reason reported by user of each of the three approaches was for "general wellness or disease prevention." The majority of users of all three health approaches reported that they perceived this use improved their overall health and made them feel better. Yoga users perceived higher rates of all of the self-reported wellness-related health outcomes than users of natural product supplements or spinal manipulation. PMID- 26556395 TI - Muller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy. AB - Retinal gliosis is characterized by biochemical and physiological changes that often lead to Muller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Muller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Muller cell line MIO-M1 and four human Muller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays. Comparative analysis of the expression of inflammatory factors showed that in comparison with normal retina, gliotic retina exhibited greater than twofold increase in 24/102 factors examined by semiquantitative arrays, and a significant increase in 19 out of 27 factors assessed by quantitative methods (P < 0.05 to P < 0.001). It was observed that with the exception of some chemotactic factors, the majority of cytokines and inflammatory factors were produced by Muller glia in vitro and included G-CSF, MCP-1, PDGF-bb, RANTES, VEGF, and TGFbeta2. These results showed that a large number of inflammatory factors expressed by Muller glia in vitro are upregulated in the gliotic retina, suggesting that targeting the production of inflammatory factors by Muller glia may constitute a valid approach to prevent neural damage during retinal gliosis and this merits further investigations. PMID- 26556397 TI - Liraglutide Improves Glycemic and Blood Pressure Control and Ameliorates Progression of Left Ventricular Hypertrophy in Patients with Type 2 Diabetes Mellitus on Peritoneal Dialysis. AB - Diabetes mellitus (DM) is a multifactorial disease associated with cardiovascular complications. Patients undergoing peritoneal dialysis also experience an increased incidence of cardiovascular disease. To prevent progression of cardiovascular complications in DM patients, glycemic control is important. In this study, we examined the efficacy and safety of the glucagon-like peptide analog liraglutide for treating type 2 diabetes patients undergoing peritoneal dialysis. Sixteen type 2 diabetes patients on peritoneal dialysis were enrolled. Before liraglutide initiation, 11 patients were on insulin therapy, three were on oral antidiabetic agents, and two were on diet therapy. Of the 16 patients, 12 had switched to liraglutide because of severe hypoglycemia and four because of hyperglycemia. Echocardiography was performed at baseline and 12 months after liraglutide initiation. Hemoglobin A1c, glycosylated albumin, and fasting/postprandial glucose levels gradually decreased after liraglutide initiation. After 6 and 12 months of treatment, postprandial glucose levels showed a significant difference from baseline. Moreover, the mean daily glucose level and glycemic fluctuations decreased. Systolic blood pressure upon waking also decreased. In addition, after 12 months, left ventricular mass index (LVMI) decreased and left ventricular ejection fraction increased. Changes in LVMI positively correlated with morning systolic blood pressure and fasting glucose levels. One patient restarted insulin because of anorexia but severe hypoglycemia was not observed. These findings suggest that liraglutide therapy in type 2 diabetes patients undergoing peritoneal dialysis is safe and effective for decreasing glucose levels, glycemic fluctuations, and blood pressure, apart from improving left ventricular function. PMID- 26556398 TI - Controllable generation and encapsulation of alginate fibers using droplet-based microfluidics. AB - Herein we demonstrate the segmentation of alginate solution streams to generate alginate fibers of precisely controllable lengths between 200 and 1000 MUm. Moreover, we demonstrate the subsequent encapsulation of the formed fibers within pL-volume microdroplets, produced within the same microfluidic device, in a direct manner. Finally, we show immediate and complete on-chip gelation of alginate fibers in a rapid and reproducible fashion. PMID- 26556399 TI - Rural and remote young people's health career decision making within a health workforce development program: a qualitative exploration. AB - INTRODUCTION: One strategy aimed at resolving ongoing health workforce shortages in rural and remote settings has been to implement workforce development initiatives involving the early activation and development of health career aspirations and intentions among young people in these settings. This strategy aligns with the considerable evidence showing that rural background is a strong predictor of rural practice intentions and preferences. The Broken Hill Regional Health Career Academy Program (BHRHCAP) is an initiative aimed at addressing local health workforce challenges by helping young people in the region develop and further their health career aspirations and goals. This article reports the factors impacting on rural and remote youths' health career decision-making within the context of a health workforce development program. METHODS: Data were collected using interviews and focus groups with a range of stakeholders involved in the BHRHCAP including local secondary school students, secondary school teachers, career advisors, school principals, parents, and pre-graduate health students undertaking a clinical placement in Broken Hill, and local clinicians. Data interpretation was informed by the theoretical constructs articulated within socio cognitive career theory. RESULTS: Young people's career decision-making in the context of a local health workforce development program was influenced by a range of personal, contextual and experiential factors. These included personal factors related to young people's career goals and motivations and their confidence to engage in career decision-making, contextual factors related to BHRHCAP program design and structure as well as the visibility and accessibility of health career pathways in a rural setting, and experiential factors related to the interaction and engagement between young people and role models or influential others in the health and education sectors. CONCLUSIONS: This study provided theoretical insight into the broader range of interrelating and complex personal, contextual and experiential factors impacting on rural and remote youths' career decision-making within a health workforce development initiative. PMID- 26556400 TI - Novel screening techniques for ion channel targeting drugs. AB - Ion channels are integral membrane proteins that regulate the flux of ions across the cell membrane. They are involved in nearly all physiological processes, and malfunction of ion channels has been linked to many diseases. Until recently, high-throughput screening of ion channels was limited to indirect, e.g. fluorescence-based, readout technologies. In the past years, direct label-free biophysical readout technologies by means of electrophysiology have been developed. Planar patch-clamp electrophysiology provides a direct functional label-free readout of ion channel function in medium to high throughput. Further electrophysiology features, including temperature control and higher-throughput instruments, are continually being developed. Electrophysiological screening in a 384-well format has recently become possible. Advances in chip and microfluidic design, as well as in cell preparation and handling, have allowed challenging cell types to be studied by automated patch clamp. Assays measuring action potentials in stem cell-derived cardiomyocytes, relevant for cardiac safety screening, and neuronal cells, as well as a large number of different ion channels, including fast ligand-gated ion channels, have successfully been established by automated patch clamp. Impedance and multi-electrode array measurements are particularly suitable for studying cardiomyocytes and neuronal cells within their physiological network, and to address more complex physiological questions. This article discusses recent advances in electrophysiological technologies available for screening ion channel function and regulation. PMID- 26556401 TI - Dynamic global sensitivity analysis in bioreactor networks for bioethanol production. AB - Dynamic global sensitivity analysis (GSA) was performed for three different dynamic bioreactor models of increasing complexity: a fermenter for bioethanol production, a bioreactors network, where two types of bioreactors were considered: aerobic for biomass production and anaerobic for bioethanol production and a co-fermenter bioreactor, to identify the parameters that most contribute to uncertainty in model outputs. Sobol's method was used to calculate time profiles for sensitivity indices. Numerical results have shown the time variant influence of uncertain parameters on model variables. Most influential model parameters have been determined. For the model of the bioethanol fermenter, MUmax (maximum growth rate) and Ks (half-saturation constant) are the parameters with largest contribution to model variables uncertainty; in the bioreactors network, the most influential parameter is MUmax,1 (maximum growth rate in bioreactor 1); whereas lambda (glucose-to-total sugars concentration ratio in the feed) is the most influential parameter over all model variables in the co fermentation bioreactor. PMID- 26556402 TI - Bio-oil production of softwood and hardwood forest industry residues through fast and intermediate pyrolysis and its chromatographic characterization. AB - Bio-oils were produced through intermediate (IP) and fast pyrolysis (FP), using Eucalyptus sp. (hardwood) and Picea abies (softwood), wood wastes produced in large scale in Pulp and Paper industries. Characterization of these bio-oils was made using GC/qMS and GC*GC/TOFMS. The use of GC*GC provided a broader characterization of bio-oils and it allowed tracing potential markers of hardwood bio-oil, such as dimethoxy-phenols, which might co-elute in 1D-GC. Catalytic FP increased the percentage of aromatic hydrocarbons in P. abies bio-oil, indicating its potential for fuel production. However, the presence of polyaromatic hydrocarbons (PAH) draws attention to the need of a proper management of pyrolysis process in order to avoid the production of toxic compounds and also to the importance of GC*GC/TOFMS use to avoid co-elutions and consequent inaccuracies related to identification and quantification associated with GC/qMS. Ketones and phenols were the major bio-oil compounds and they might be applied to polymer production. PMID- 26556403 TI - Polarized potential and electrode materials implication on electro-fermentative di-hydrogen production: Microbial assemblages and hydrogenase gene copy variation. AB - This study examined the changes in microbial diversity in response to different electrode materials viz., stainless steel mesh (SS) and graphite plate as anodes in two microbial electrolysis cell (MEC) each poised at 0.2V, 0.4V, 0.6V and 0.8V. Changes in microbiota prior to and after pretreatment along with microbiota enriched in response to various poised potentials with SS and graphite are monitored by 16S rRNA gene based DGGE profiling. Significant shifts in microbial community were noticed at all these experimental conditions. Correspondingly, the level of hydrogenase belonging to genera Bacillus, Pseudomonas, Rhodopseudomonas and Clostridium was studied by quantitative real time PCR (RT-PCR) at various applied potentials. DGGE based 16S rRNA gene profiling revealed enriched members belonging to phylum Firmicutes predominantly present at 0.8V in both MECs contributing to high hydrogen production. This study first time explored the growth behavior of mixed consortia in response to poised potentials and electrode materials. PMID- 26556404 TI - New insights into shear-sensitivity in dinoflagellate microalgae. AB - A modification of a flow contraction device was used to subject shear-sensitive microalgae to well-defined hydrodynamic forces. The aim of the study was to elucidate if the inhibition of shear-induced growth commonly observed in dinoflagellate microalgae is in effect due to cell fragility that results in cell breakage even at low levels of turbulence. The microalgae assayed did not show any cell breakage even at energy dissipation rates (EDR) around 10(12)Wm(-3), implausible in culture devices. Conversely, animal cells, tested for comparison purposes, showed high physical cell damage at average EDR levels of 10(7)Wm(-3). Besides, very short exposures to high levels of EDR promoted variations in the membrane fluidity of the microalgae assayed, which might trigger mechanosensory cellular mechanisms. Average EDR values of only about 4.10(5)Wm(-3) increased cell membrane fluidity in microalgae whereas, in animal cells, they did not. PMID- 26556405 TI - Enhanced production and application of acidothermophilic Streptomyces cellulase. AB - An efficient cellulolytic and acidothermophilic actinobacterium was isolated from soil, adhered to decomposing tree bark and was identified as Streptomyces DSK59. Screening of synthetic media and the media components identified that, a medium based on starch casein minerals containing carboxy methyl cellulose (CMC) and beef extract (BE) could support enhanced cellulase production by the organism. CMC, BE, NaCl, temperature and pH were accounted as significant for cellulase production and these were optimized using a response surface central composite design (CCD). Optimization of cellulase production resulted in an enhancement of endoglucanase activity to 27IUml(-1). Acidothermophillic Streptomyces cellulase was found to be efficient for hydrolysis of pretreated sorghum stover and liberated 0.413gg(-1) of total reducing sugars which was higher than previously reported sugar yields obtained using fungal enzymes. PMID- 26556408 TI - Hemodynamic Surveillance of Ventricular Pacing Effectiveness with the Transvalvular Impedance Sensor. AB - The Transvalvular Impedance (TVI) is derived between atrial and ventricular pacing electrodes. A sharp TVI increase in systole is an ejection marker, allowing the hemodynamic surveillance of ventricular stimulation effectiveness in pacemaker patients. At routine follow-up checks, the ventricular threshold test was managed by the stimulator with the supervision of a physician, who monitored the surface ECG. When the energy scan resulted in capture loss, the TVI system must detect the failure and increase the output voltage. A TVI signal suitable to this purpose was present in 85% of the tested patients. A total of 230 capture failures, induced in 115 patients in both supine and sitting upright positions, were all promptly recognized by real-time TVI analysis (100% sensitivity). The procedure was never interrupted by the physician, as the automatic energy regulation ensured full patient's safety. The pulse energy was then set at 4 times the threshold to test the alarm specificity during daily activity (sitting, standing up, and walking). The median prevalence of false alarms was 0.336%. The study shows that TVI-based ejection assessment is a valuable approach to the verification of pacing reliability and the autoregulation of ventricular stimulation energy. PMID- 26556407 TI - Advances in Proteomic Technologies and Its Contribution to the Field of Cancer. AB - Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies are not widely available for most cancers. Precision care plans still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics is continuing to make major strides in the discovery of fundamental biological processes as well as more recent transition into an assay platform capable of measuring hundreds of proteins in any biological system. As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine. The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience. Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated. Here I describe contribution of proteomics in general and biological mass spectrometry in particular to cancer research, as well as related major technical and conceptual developments in the field. PMID- 26556409 TI - Comorbid Obsessive-Compulsive Symptoms in Schizophrenia: Insight into Pathomechanisms Facilitates Treatment. AB - Insight into the biological pathomechanism of a clinical syndrome facilitates the development of effective interventions. This paper applies this perspective to the important clinical problem of obsessive-compulsive symptoms (OCS) occurring during the lifetime diagnosis of schizophrenia. Up to 25% of schizophrenia patients suffer from OCS and about 12% fulfil the diagnostic criteria of obsessive-compulsive disorder (OCD). This is accompanied by marked subjective burden of disease, high levels of anxiety, depression and suicidality, increased neurocognitive impairment, less favourable levels of social and vocational functioning, and greater service utilization. Comorbid patients can be assigned to heterogeneous subgroups. It is assumed that second generation antipsychotics (SGAs), most importantly clozapine, might aggravate or even induce second-onset OCS. Several epidemiological and pharmacological arguments support this assumption. Specific genetic risk factors seem to dispose patients with schizophrenia to develop OCS and risk-conferring polymorphisms has been defined in SLC1A1, BDNF, DLGAP3, and GRIN2B and in interactions between these individual genes. Further research is needed with detailed characterization of large samples. In particular interactions between genetic risk constellations, pharmacological and psychosocial factors should be analysed. Results will further define homogeneous subgroups, which are in need for differential causative interventions. In clinical practise, schizophrenia patients should be carefully monitored for OCS, starting with at-risk mental states of psychosis and longitudinal follow-ups, hopefully leading to the development of multimodal therapeutic interventions. PMID- 26556410 TI - Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus. AB - Encapsulation of pancreatic islets has been proposed and investigated for over three decades to improve islet transplantation outcomes and to eliminate the side effects of immunosuppressive medications. Of the numerous encapsulation systems developed in the past, microencapsulation have been studied most extensively so far. A wide variety of materials has been tested for microencapsulation in various animal models (including nonhuman primates or NHPs) and some materials were shown to induce immunoprotection to islet grafts without the need for chronic immunosuppression. Despite the initial success of microcapsules in NHP models, the combined use of islet transplantation (allograft) and microencapsulation has not yet been successful in clinical trials. This review consists of three sections: introduction to islet transplantation, transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus (T1DM), and present challenges and future perspectives. PMID- 26556412 TI - Identifying a Framework for Hope in Order to Establish the Importance of Generalised Hopes for Individuals Who Have Suffered a Stroke. AB - Hope and hopelessness are important psychological constructs that physiotherapists should consider when working with patients who have experienced a stroke. The view of hope in rehabilitation is often focused around the concept of goals and how hope works within this framework. However, the current paper proposes a broader framework for hope and the importance of a more generalised view of understanding why a certain hope exists or is identified by a patient. A narrative review using an a priori thematic analysis was undertaken to consider how more generalised hopes are expressed by individuals who have suffered a stroke. An electronic search of 4 databases from inception until April 2014 was undertaken. Qualitative articles were included if they considered the concept of hope for patients who had suffered a stroke. The results identified three themes which included (1) consideration of the patient's identity/identities, (2) meaningful activities, experiences, and interactions, and (3) the experience of suffering and need for relief. An awareness of patients' generalised hopes should be a priority for HCPs. Detailed implications for HCPs are identified within the discussion. PMID- 26556411 TI - Percutaneous Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: From Experiment to Standard of Care. AB - Hypertrophic cardiomyopathy (HCM) is one of the more common hereditary cardiac conditions. According to presence or absence of outflow obstruction at rest or with provocation, a more common (about 60-70%) obstructive type of the disease (HOCM) has to be distinguished from the less common (30-40%) nonobstructive phenotype (HNCM). Symptoms include exercise limitation due to dyspnea, angina pectoris, palpitations, or dizziness; occasionally syncope or sudden cardiac death occurs. Correct diagnosis and risk stratification with respect to prophylactic ICD implantation are essential in HCM patient management. Drug therapy in symptomatic patients can be characterized as treatment of heart failure with preserved ejection fraction (HFpEF) in HNCM, while symptoms and the obstructive gradient in HOCM can be addressed with beta-blockers, disopyramide, or verapamil. After a short overview on etiology, natural history, and diagnostics in hypertrophic cardiomyopathy, this paper reviews the current treatment options for HOCM with a special focus on percutaneous septal ablation. Literature data and the own series of about 600 cases are discussed, suggesting a largely comparable outcome with respect to procedural mortality, clinical efficacy, and long-term outcome. PMID- 26556415 TI - Malaria, Typhoid Fever, and Their Coinfection among Febrile Patients at a Rural Health Center in Northwest Ethiopia: A Cross-Sectional Study. AB - Background. Malaria and typhoid fever are major public health problems in tropical and subtropical countries. People in endemic areas are at risk of contracting both infections concurrently. Objectives. The study was aimed at determining the prevalence and associated risk factors of malaria, typhoid, and their coinfection among febrile patients. Methods. A cross-sectional study was conducted on 200 febrile patients suspected for malaria and/or typhoid fever from April to May, 2013, at Ayinba Health Center, Northwest Ethiopia. Blood samples were collected for blood culture, Widal test, and blood film preparation. Data were analyzed using SPSS version 20 statistical software. Results. The prevalence of malaria was 36.5% (n = 73). Among these 32 (43.8%), 30 (41.1%) and 11 (15.1%) were positive for P. falciparum, P. vivax, and mixed infections, respectively. The seroprevalence of typhoid fever was 38 (19%), but 1 (0.5%) with blood culture. Malaria typhoid fever coinfection was 13 (6.5%). 2-5-year-old children and poor hand washing habit were significantly associated with malaria and typhoid infection, respectively (P < 0.05). Conclusions. The prevalence of malaria and typhoid fever was found high. Further studies should be done on the other determinants of malaria and typhoid fever coinfection in different seasons and different study areas. PMID- 26556414 TI - Treatment Alternatives to Negotiate Peri-Implantitis. AB - Peri-implant diseases are becoming a major health issue in dentistry. Despite the magnitude of this problem and the potential grave consequences, commonly acceptable treatment protocols are missing. Hence, the present paper reviews the literature treatment of peri-implantitis in order to explore their benefits and limitations. Treatment of peri-implantitis may include surgical and nonsurgical approaches, either individually or combined. Nonsurgical therapy is aimed at removing local irritants from the implants' surface with or without surface decontamination and possibly some additional adjunctive therapies agents or devices. Systemic antibiotics may also be incorporated. Surgical therapy is aimed at removing any residual subgingival deposits and additionally reducing the peri implant pockets depth. This can be done alone or in conjunction with either osseous respective approach or regenerative approach. Finally, if all fails, explantation might be the best alternative in order to arrest the destruction of the osseous structure around the implant, thus preserving whatever is left in this site for future reconstruction. The available literature is still lacking with large heterogeneity in the clinical response thus suggesting possible underlying predisposing conditions that are not all clear to us. Therefore, at present time treatment of peri-implantitis should be considered possible but not necessarily predictable. PMID- 26556413 TI - Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis. AB - Peritoneal dialysis (PD) is a therapeutic option for the treatment of end-stage renal disease and is based on the use of the peritoneum as a semipermeable membrane for the exchange of toxic solutes and water. Long-term exposure of the peritoneal membrane to hyperosmotic PD fluids causes inflammation, loss of the mesothelial cells monolayer, fibrosis, vasculopathy, and angiogenesis, which may lead to peritoneal functional decline. Peritonitis may further exacerbate the injury of the peritoneal membrane. In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration. Factors contributing to the bioincompatibility of classical PD fluids include the high content of glucose/glucose degradation products (GDPs) and their acidic pH. New generation low-GDPs-neutral pH fluids have improved biocompatibility resulting in better preservation of the peritoneum. However, standard glucose-based fluids are still needed, as biocompatible solutions are expensive for many potential users. An alternative approach to preserve the peritoneal membrane, complementary to the efforts to improve fluid biocompatibility, is the use of pharmacological agents protecting the mesothelium. This paper provides a comprehensive review of recent advances that point to the EMT of mesothelial cells as a potential therapeutic target to preserve membrane function. PMID- 26556416 TI - Assessment of the Self-Perception of Dental Appearance, Its Comparison with Orthodontist's Assessment and Demand for Treatment in Eastern Nepalese Patients. AB - Aims. The aim of this study was to assess the self-perception of dental appearance among Eastern Nepalese patients using aesthetic component (AC) of the index of orthodontic treatment need (IOTN) and to compare it with that of an orthodontist's assessment using the same scale and determine whether gender, area of residence, and level of education influence subject's self-perception and orthodontist's ratings. Methods. A total of 252 subjects (equal number of male and female) were conveniently selected. The average ages of subjects were 22.33 +/- 2.114 years. The level of subject's perception and orthodontist's assessment was analyzed by nonparametric Chi square test. Kappa coefficient was done to verify its agreement. The Spearman's correlation test was used to check the association of educational level and age. Mann-Whitney test was used to check the associations of sex and areas of residence. Results. The demand for treatment was significantly associated with the perception of the subject and orthodontist's assessment. However, age, gender, and educational level were statistically insignificant in influencing subject perception and orthodontist's assessment. Conclusion. Patient's self-perception should be given equal importance while planning orthodontic treatment. PMID- 26556417 TI - Ensuring Confidentiality of Geocoded Health Data: Assessing Geographic Masking Strategies for Individual-Level Data. AB - Public health datasets increasingly use geographic identifiers such as an individual's address. Geocoding these addresses often provides new insights since it becomes possible to examine spatial patterns and associations. Address information is typically considered confidential and is therefore not released or shared with others. Publishing maps with the locations of individuals, however, may also breach confidentiality since addresses and associated identities can be discovered through reverse geocoding. One commonly used technique to protect confidentiality when releasing individual-level geocoded data is geographic masking. This typically consists of applying a certain amount of random perturbation in a systematic manner to reduce the risk of reidentification. A number of geographic masking techniques have been developed as well as methods to quantity the risk of reidentification associated with a particular masking method. This paper presents a review of the current state-of-the-art in geographic masking, summarizing the various methods and their strengths and weaknesses. Despite recent progress, no universally accepted or endorsed geographic masking technique has emerged. Researchers on the other hand are publishing maps using geographic masking of confidential locations. Any researcher publishing such maps is advised to become familiar with the different masking techniques available and their associated reidentification risks. PMID- 26556418 TI - An Average Body Circumference Can Be a Substitute for Body Mass Index in Women. AB - Introduction. Significant correlations between BMI and some body circumferences have been previously reported. In this study we investigated if the average of the sum of eight body circumferences can be a substitute for BMI. Patients and Methods. BMI and eight body circumferences (neck, waist, hip, arm, forearm, wrist, thigh, and ankle) were measured in 193 apparently healthy women aged 20 83, and within a wide range of BMI. Women with BMI <= 24.9 were designated as normal, with BMI 25-29.9 as overweight and with BMI >= 30 as obese. The relationship of the average body circumference (ABC) of the sum of the eight circumferences, and of each individual circumference with BMI, was evaluated. Results. ABC had the strongest correlation with BMI (r = 0.95, P < 0.001) among all the circumferences tested. Hip circumference had the strongest correlation with BMI (r = 0.89, P < 0.001) among the circumferences of individual body sites. Receiver-Operator Characteristic analysis showed that women with ABC > 44.0 cm could be recognized as having BMI >= 25 with sensitivity 90.2% and specificity 88.5%, while women with ABC > 47.1 cm could be diagnosed as having BMI >= 30 with sensitivity 92.2% and specificity 91.5%. Conclusion. An average body circumference strongly correlated with BMI in women and can serve as a surrogate of BMI. PMID- 26556419 TI - Coexistence of Upper Airway Obstruction and Primary and Secondary Enuresis Nocturna in Children and the Effect of Surgical Treatment for the Resolution of Enuresis Nocturna. AB - Objective. The aim of this study is to investigate the coexistence of upper airway obstruction (UAO) and primary enuresis nocturna (PEN) and secondary enuresis nocturna (SEN) in children. Besides, the efficacy of surgery on resolution of enuresis nocturna is evaluated. Materials and Methods. The children with PEN and SEN were included in the first group and investigated for UAO in the Department of Otorhinolaryngology. During the same period, children who had been planned for an operation to treat UAO over 5 years old were included in the second group and were evaluated in the Department of Urology for PEN and SEN before the operation. Results. A hundred patients completed the study (50 patients in Group 1, 50 patients in Group 2). According to the otolaryngologic examination, 20 of 25 PEN patients and 9 of 25 SEN patients also had UAO. The difference was statistically different (P < 0.05). The second group consisted of fifty patients on the surgery list for upper airway obstructive pathologies. Coexistence of PEN and SEN is found in 12 and 3 of children, respectively. These ratios were statistically significant (P < 0.05). The improvement rate of PEN and SEN after operation in the second group was 83.3% and 33.3%, respectively. The difference was statistically significant (P < 0.05). Conclusion. There is a strong relationship between PEN and UAO, but it cannot be declared for SEN patients. UAO should be kept in mind as a possible etiologic factor for PEN. PMID- 26556420 TI - Quality of Life among Egyptian Patients with Upper and Lower Limb Amputation: Sex Differences. AB - Background. Limb amputation is a life-changing event that can cause significant disruptions in many important areas of existence. Aim of this study. To evaluate the quality of life (QOL) of patients with limb amputation and identify the factors affecting the quality of life of patients with limb amputation among Egyptian patients. Research Design. It was a descriptive exploratory design. Setting. The study was conducted in Orthopedics and Surgical Department in Emergency Hospital at Mansoura University Hospitals. Sample. A sample of convenience of 100 adult male and female patients who met the inclusion criteria was included. Tools. (a) Structured interview questionnaire (SIQ) was used to collect personal data, (b) short form (36) health status questionnaires: this part was utilized to assess the quality of life among Egyptian patients with amputation. Results. The result of this study indicates that most participants experienced a change in the quality of life. There is a statistically significant difference between total QOL aspects and each of the following: age, gender, educational level, and type of work. Conclusion. Limb amputation tends to cause increased disability for those amputated patients. The age, gender, place of amputation, and marital status are found as statistically significant factors with physical component and psychological component. PMID- 26556421 TI - A Study on the Association between Low Maternal Serum Magnesium Level and Preterm Labour. AB - Objectives. The study was aimed to assess the association between low maternal serum magnesium levels and preterm labour. Methods. It is a cross-sectional case control study in which eligible participants were pregnant women admitted in labour within the labour ward complex of a Lagos tertiary hospital. Relevant data were extracted from the case records of these women and blood samples were obtained from all participants and serum magnesium levels measured. Results. The study showed that 36% of the study patients had varying degrees of hypomagnesaemia. The relative risk indicates that preterm labour is 1.83 times higher among the patients with low serum magnesium (less than 1.6 mg/dL). The mean difference in serum magnesium levels in both groups was statistically significant (P<0.05). Conclusion. We can infer that low serum magnesium (hypomagnesaemia) is associated with preterm onset of labour. We can, also from this finding, formulate a proposition that would help in preventing preterm labour and birth with the use of prophylactic oral magnesium supplementation among patients with higher risk for development of preterm labour. PMID- 26556423 TI - Evaluating the Reproducibility of Motion Analysis Scanning of the Spine during Walking. AB - The Formetric 4D dynamic system (Diers International GmbH, Schlangenbad, Germany) is a rasterstereography based imaging system designed to evaluate spinal deformity, providing radiation-free imaging of the position, rotation, and shape of the spine during the gait cycle. Purpose. This study was designed to evaluate whether repeated measurements with the Formetric 4D dynamic system would be reproducible with a standard deviation of less than +/- 3 degrees. This study looked at real-time segmental motion, measuring kyphosis, lordosis, trunk length, pelvic, and T4 and L1 vertebral body rotation. Methods. Twenty healthy volunteers each underwent 3 consecutive scans. Measurements for kyphosis, lordosis, trunk length, and rotations of T4, L1, and the pelvis were recorded for each trial. Results. The average standard deviations of same-day repeat measurements were within +/- 3 degrees with a range of 0.51 degrees to 2.3 degrees. Conclusions. The surface topography system calculated reproducible measurements with error ranges comparable to the current gold standard in dynamic spinal motion analysis. Therefore, this technique should be considered of high clinical value for reliably evaluating segmental motion and spinal curvatures and should further be evaluated in the setting of adolescent idiopathic scoliosis. PMID- 26556422 TI - Current Options for Determining Fracture Union. AB - Determining whether a bone fracture is healed is one of the most important and fundamental clinical determinations made in orthopaedics. However, there are currently no standardized methods of assessing fracture union, which in turn has created significant disagreement among orthopaedic surgeons in both clinical and research settings. An extensive amount of research has been dedicated to finding novel and reliable ways of determining healing with some promising results. Recent advancements in imaging techniques and introduction of new radiographic scores have helped decrease the amount of disagreement on this topic among physicians. The knowledge gained from biomechanical studies of bone healing has helped us refine our tools and create more efficient and practical research instruments. Additionally, a deeper understanding of the molecular pathways involved in the bone healing process has led to emergence of serologic markers as possible candidates in assessment of fracture union. In addition to our current physician centered methods, patient-centered approaches assessing quality of life and function are gaining popularity in assessment of fracture union. Despite these advances, assessment of union remains an imperfect practice in the clinical setting. Therefore, clinicians need to draw on multiple modalities that directly and indirectly measure or correlate with bone healing when counseling patients. PMID- 26556424 TI - Prevalence and Aetiology of Left Ventricular Thrombus in Patients Undergoing Transthoracic Echocardiography at the University of Maiduguri Teaching Hospital. AB - Objectives. We sought to determine the prevalence and aetiology of LVT among patients undergoing echocardiography. Methods. We reviewed case notes and echocardiographic data of patient diagnosed with LVT using noncontrast transthoracic echocardiography. Definition of various conditions was made using standard guidelines. Mean +/- SD were derived for continuous variables and comparison was made using Student's t-test. Results. Total of 1302 transthoracic echocardiograms were performed out of which 949 adult echocardiograms were considered eligible. Mean age of all subjects with abnormal echocardiograms was 44.73 (16.73) years. Abnormalities associated with LVT were observed in 782/949 (82.40%) subjects among whom 84/782 (8.85%) had LVT. The highest prevalence of 39.29% (33/84) was observed in patients with dilated cardiomyopathy, followed by myocardial infarction with a prevalence of 29.76% (25/84). Peripartum cardiomyopathy accounted for 18/84 (21.43%) cases with some having multiple thrombi, whereas hypertensive heart disease was responsible for 6/84 (7.14%) cases. The lowest prevalence of 2.38% (2/84) was observed in those with rheumatic heart disease. Left ventricular EF of <35% was recorded in 55/84 (65.48%). Conclusions. Left ventricular thrombus is common among patients undergoing echo, with dilated cardiomyopathy being the most common underlying aetiology followed by myocardial infarction. Multiple LVTs were documented in peripartum cardiomyopathy. PMID- 26556425 TI - Sepsis Associated Encephalopathy. AB - Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis. PMID- 26556426 TI - Reconstructive Surgery for Head and Neck Cancer Patients. AB - The field of head and neck surgery has gone through numerous changes in the past two decades. Microvascular free flap reconstructions largely replaced other techniques. More importantly, there has been a paradigm shift toward seeking not only to achieve reliable wound closure to protect vital structures, but also to reestablish normal function and appearance. The present paper will present an algorithmic approach to head and neck reconstruction of various subsites, using an evidence-based approach wherever possible. PMID- 26556428 TI - Presumed Virus-Induced Punctal Occlusion. AB - Purpose. To investigate viral infection as a cause of punctal stenosis in individuals without any ocular or systemic risk factors. Methods. The study group comprised patients with no known cause for punctal occlusion who underwent surgery at one medical center during a one-year period. Excised tissue was subjected to histological examination, PCR, and nested PCR testing for common viruses (adenovirus, influenza A and B, enterovirus, varicella-zoster, CMV, herpes simplex types 1 and 2, Epstein-Barr virus, and parainfluenza type 1). Results. All nine patients identified were female, 20-38 years of age. The three snip-procedure resolved tearing in eight of them. All excised samples showed chronic mononuclear inflammation compatible with viral infection or with viral infection immune inflammatory reaction. PCR testing was negative for all the viruses examined; however, nested PCR was positive in three patients. Conclusion. This study supports the proposition that punctal occlusion in young healthy females may be due to viral infection. PMID- 26556427 TI - Chemokines Referee Inflammation within the Central Nervous System during Infection and Disease. AB - The discovery that chemokines and their receptors are expressed by a variety of cell types within the normal adult central nervous system (CNS) has led to an expansion of their repertoire as molecular interfaces between the immune and nervous systems. Thus, CNS chemokines are now divided into those molecules that regulate inflammatory cell migration into the CNS and those that initiate CNS repair from inflammation-mediated tissue damage. Work in our laboratory throughout the past decade has sought to elucidate how chemokines coordinate leukocyte entry and interactions at CNS endothelial barriers, under both homeostatic and inflammatory conditions, and how they promote repair within the CNS parenchyma. These studies have identified several chemokines, including CXCL12 and CXCL10, as critical regulators of leukocyte migration from perivascular locations. CXCL12 additionally plays an essential role in promoting remyelination of injured white matter. In both scenarios we have shown that chemokines serve as molecular links between inflammatory mediators and other effector molecules involved in neuroprotective processes. PMID- 26556431 TI - Effects of Atorvastatin on Oxidative Stress Biomarkers and Mitochondrial Morphofunctionality in Hyperfibrinogenemia-Induced Atherogenesis. AB - Relationship between hyperfibrinogenemia (HF), oxidative stress, and atherogenesis was established. Effect of atorvastatin (Ator) was assessed. Wistar male (6 months) rats were studied: Ctr, control, without HF induction; Ctr-Ator, without HF treated with atorvastatin; AI, atherogenesis induced, and AI-Ator, atherogenesis induced and treated with atorvastatin. Atherogenesis was induced by daily adrenaline injection (0.1 mL/day/rat) for 90 days; treatment started 15 days after induction. Fibrinogen (mg/dL) and nitric oxide (NO) were measured in plasma (mM) and superoxide dismutase (SOD) (U/mL) in red cell lysate by spectrophotometry. Slices of aorta were analyzed by electron microscopy (EM). ANOVA and chi-square test were used; P < 0.05 was established. There were no significant differences between Ctr and Ctr-Atorv in fibrinogen, NO, and SOD values. Comparing Ctr with AI an increase of fibrinogen is observed (P < 0.001), but it decreased after administration of atorvastatin in AI-Ator (P < 0.001). NO diminished in AI relative to Ctr and increased in AI-Ator (P < 0.001). SOD showed an increase in AI and AI-Ator compared to Ctr (P < 0.001). EM revealed expansion of intermembrane space and disorganization of crests in AI. In AI-Ator mitochondrial areas and diameters were similar to control. Atorvastatin normalizes HF, stabilizes NO, increases SOD, and produces a partial regression of mitochondrial lesions. PMID- 26556432 TI - Ivacaftor Therapy in CF Patients: Single Center Experience. AB - Ivacaftor is the first novel cystic fibrosis pharmaceutical that acts at the molecular level to potentiate cystic fibrosis transmembrane conductance regulator (CFTR) function and was first approved for clinical use in 2012. We are sharing our single center experience of five patients: four from pediatric age group and one adult patient. All patients had both subjective and objective improvements in their health. Despite established lung disease, our patients had significant improvement in both their FEV1 (forced expiratory volume in 1 second) and FEF25 75 and BMI (body mass index). Larger studies demonstrated only 6.7% improvement in mean FEV1 after starting Ivacaftor therapy but their patient population had normal lung function to begin with. In contrast our case series demonstrates that, in patients with established lung disease and diminished lung function, Ivacaftor can be expected to result in much higher recovery in lung function. Mean FEV1 improved by 35% in our case series. Ivacaftor is extremely expensive, costing $300,000 per patient per year requiring lifelong therapy, hence requiring prior authorizations from most third-party payers in the USA. The knowledge shared from our experience will be useful for other clinicians to petition healthcare policymakers on behalf of their patients. PMID- 26556429 TI - Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies. AB - Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. PMID- 26556433 TI - The Efficacy of Sucralfate and Chlorhexidine as an Oral Rinse in Patients with Recurrent Aphthous Stomatitis. AB - Aim. In this study, we compared the efficacy of sucralfate suspension with chlorhexidine as an oral rinse in patients with recurrent aphthous stomatitis (RAS) in terms of pain relief and healing time. Materials and Methods. The subjects with a complaint of recurrent oral aphthous ulcers less than 1 cm in diameter on the first day of the occurrence of the ulcer and between 20 and 40 years were included in the study. Seventy patients completed the study. The patients were randomized into two groups as SCH group and CHX group. Changes in pain scores, healing time, and side effects of the treatments were evaluated. Results. The mean value of pain scores on the days after the treatment from the first day to the seventh day was significantly higher in CHX group than SCH group (P <= 0.05). On the seventh day after the treatment, the ulcers were completely reepithelialized in 23 patients in SCH group and in 19 patients in CHX group. The difference was statistically significant (P <= 0.05). In SCH group, the mean healing time of ulcers was 1.97 +/- 1.56 days whereas it was 2.80 +/- 3.00 days in CHX group. The difference was statistically significant (P <= 0.05). No side effects were recorded in either of the groups. Conclusion. Topical sucralfate suspension is an easy, safe, inexpensive, and effective treatment option for RAS to obtain pain relief and shorten the healing time of oral ulcers. PMID- 26556430 TI - Targeting BCL2-Proteins for the Treatment of Solid Tumours. AB - Due to their central role in the regulation of apoptosis, the antiapoptotic BCL2 proteins are highly promising targets for the development of novel anticancer treatments. To this end, several strategies have been developed to inhibit BCL2, BCL-XL, BCL-w, and MCL1. While early clinical trials in haematological malignancies demonstrated exciting single-agent activity of BCL2-inhibitors, the response in solid tumours was limited, indicating that, in solid tumours, different strategies have to be developed in order to successfully treat patients with BCL2-inhibitors. In this review, the function of the different antiapoptotic BCL2-proteins and their role in solid tumours will be discussed. In addition, a comprehensive analysis of current small molecules targeting these antiapoptotic BCL2-proteins (e.g., ABT-737, ABT-263, ABT-199, TW-37, sabutoclax, obatoclax, and MIM1) will be provided including a discussion of the results of any clinical trials. This analysis will summarise the potential of BCL2-inhibitors for the treatment of solid tumours and will unravel novel approaches to utilise these inhibitors in clinical applications. PMID- 26556434 TI - Amphiphilic Cyanine-Platinum Conjugates as Fluorescent Nanodrugs. AB - Two fluorescent nanomedicines based on small molecular cyanine-platinum conjugates have been prepared via a nanoprecipitation method and characterized by transmission electron microscopy (TEM) as well as dynamic light scattering (DLS). The conjugates exhibited an enhanced fluorescence in their nanoparticle formulation compared to that in solution. The nanomedicines could be endocytosed by cancer cells as revealed by confocal laser scanning microscopy (CLSM) and showed high cellular proliferation inhibition. Fluorescent platinum nanomedicines prepared directly from small molecules could be an alternative strategy for developing new drugs with simultaneous cellular imaging and cancer therapy functions. PMID- 26556435 TI - Antimicrobial Effect of Malpighia Punicifolia and Extension of Water Buffalo Steak Shelf-Life. AB - In the present study, a multiple approach was used to characterize Malpighia punicifolia extract and to evaluate its inhibitory activity against several meat spoilage bacteria. First, volatile fraction, vitamins and phenolic compounds of the extract obtained by supercritical fluid extraction were determined by GC-MS and HPLC. Then, the antimicrobial action of the extract was in vitro evaluated against Pseudomonas putida DSMZ 291(T), Pseudomonas fluorescens DSMZ 50009(T), Pseudomonas fragi DSMZ 3456(T), and Brochothrix thermosphacta DSMZ 20171(T) by the agar well diffusion assay and by the agar dilution test. Based on the results of the minimum inhibitory concentration (MIC) against the assayed bacteria, 4 different concentrations of the extract were used in a challenge test on water buffalo steaks stored for 21 d at 4 degrees C. Results of chemical analyses showed that M. punicifolia extract is characterized by the presence of several compounds, already described for their antimicrobial (phenolic acids, flavonones, and furanes) and antioxidant (ascorbic acid) properties. The in vitro detection of antimicrobial activities highlighted that the extract, used at 8% concentration, was able to inhibit all the target bacteria. Moreover, very low MIC values (up to 0.025%) were detected. In situ tests, performed on water buffalo steaks treated with the extract in the concentration range 0.025% to 0.05%, showed a strong inhibition of both intentionally inoculated bacteria and naturally occurring microorganisms. Positive results, in terms of color and odor, were also observed during the entire storage of steaks preserved with the extract. PMID- 26556437 TI - Gout tophus on an intradural fascicle: a case description. AB - STUDY DESIGN: Case report and review of literature. OBJECTIVE: Detailed description of case and review of literature to determine its uniqueness with special regard to intradural gout tophus formation without any boney attachment or underlying systemic gout. Gout tophi commonly involve the peripheral joints of the upper and lower extremities. Rarely, gout tophi are located within the spinal cord, especially without any underlying hyperuricemia. METHODS: We report the case of a 64-year-old patient presenting with radiculopathy along the right L2 dermatome and bladder dysfunction and review literature for further discussion. RESULTS: Imaging studies showed a partly calcified round intradural lesion at the level L2 without contrast enhancement. The lesion was removed via a hemilaminectomy L2. It was adherent to a dorsal sensory fascicle exiting with the L2 nerve root. The neuropathological examination showed a gout tophus. Serologic testing revealed no signs of hyperuricemia. CONCLUSION: To the best of our knowledge, this is the first report of a gout tophus originating from an intradural fascicle and without any boney attachment or underlying systemic gout. The literature is reviewed and possible pathophysiological mechanisms are discussed. PMID- 26556438 TI - Cervical subtotal en-bloc spondylectomy of C6 mesenchymal chondrosarcoma. AB - INTRODUCTION: We present a case of C6 mesenchymal chondrosarcoma and discuss safe posterior to anterior approach subtotal en-bloc spondylectomy. MATERIALS AND METHODS: A 29-year-old male consulted for our department with severe posterior neck pain doing exercise. CT scan demonstrated a primary osteolytic lesion on C6 left transverse foramen and MRI demonstrated the tumor involved C6 vertebra from layers B, C and F sectors 4-6 encasing left vertebral artery. Preoperatively neurointerventional radiology service occluded the left vertebral artery and tumor feeding artery using coil embolization. Posterior approach consist of C5-C7 laminectomy, left sided C6 and C7 nerve root sacrifice, posterior disc removal and release of C5-6-7 and posterior reconstruction. Then, position was changed to supine, and the anterior approach was followed as C5-6, C6-7 discectomy, left vertebral artery ligation and cut, longus coli resection and C6 subtotal spondylectomy with en-bloc resection of mass, mesh cage insertion and C5-C7 anterior plate fixation. During operation, frozen biopsy was performed on 8 areas (longus coli, lateral margin, anteroinferior margin, posterior margin, posterosuperior margin, C5 transverse foramen, posteroinferior margin, inferior margin) after wide resection. Tumor free margin was confirmed. RESULTS: After operation, he complained of tingling sensation of left thumb and forearm medial side, and elbow extensor motor grade was checked to 4/5 postoperatively. In the followed-up radiograph, the tumor was completely removed, and the instability of joint was not seen. As a result of observing follow-up CT at a year after the surgery, recurrence findings have not been shown up to now, and the progression of neurologic symptoms has not been shown either. CONCLUSION: Based on the Grand Round case and relevant literature, we discuss the case of mesenchymal chondrosarcoma occurring from the C6 cervical spine treated with cervical subtotal en-bloc spondylectomy. Successful en-bloc resection of the tumor was achieved using posterior to anterior approach. PMID- 26556439 TI - Role of peritoneal washing cytology in ovarian malignancies: correlation with histopathological parameters. AB - BACKGROUND: Peritoneal dissemination of ovarian tumors is a major prognostic parameter in ovarian malignancies. Analysis of peritoneal washing cytology serves as a useful predictor of ovarian surface involvement and peritoneal metastasis even in the absence of clinical omental spread. The aim of the current study is to correlate peritoneal cytology with various histologic features of ovarian cancers in our setup. METHODS: A total of 60 cases of ovarian tumors were included in the study that underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omental and lymph node sampling during 2009 till 2014 at the Liaquat National Hospital, Karachi. Any free abdominal fluid was aspirated at the time of surgery. In the absence of free fluid, peritoneal washing was done with 50-100 ml of normal saline. Four cytospin preparations were done along with a cell block preparation. Correlation of peritoneal cytology with various histologic parameters was performed. RESULTS: Out of the 60 cases of ovarian tumors involved in the study, 56 were surface epithelial tumors, 2 germ cell tumors, and 2 metastatic carcinomas. The mean tumor size was 9.6 cm. Capsular invasion was seen in 61 % of the cases, and omental metastasis in 51 % of the cases. Serous carcinoma was found to have a significantly higher frequency of positive peritoneal cytology (76.9 %) compared to endometrioid and mucinous carcinomas (44 and 25 %, respectively). A significant positive correlation was seen between positive peritoneal cytology and capsular invasion and omental metastasis with a p value of <0.001. CONCLUSIONS: Positive peritoneal washing cytology has been implemented in ovarian cancer guidelines because of its prognostic significance in ovarian tumors. In addition to being an indicator of peritoneal metastasis, positive cytology also correlates with capsular invasion and histologic type in ovarian tumors. Therefore, it should always be used as an adjunctive tool in the surgical management of ovarian tumors. PMID- 26556440 TI - Prolonged QT interval in ST-elevation myocardial infarction: predictors and prognostic value in medium-term follow-up. AB - AIMS: The prognostic role of corrected QT interval in ST-elevation myocardial infarction is still unknown. This study aims to identify the prognostic value of corrected QT interval prolongation (>=480 ms) in acute coronary syndrome. METHODS: One hundred and eighty-five consecutive patients with ST-elevation myocardial infarction were prospectively enrolled and electrocardiographic monitoring of corrected QT interval was performed during the hospitalization. RESULTS: Over a mean period of 17.6 +/- 11 months, 16 (8.6%) patients died because of cardiovascular diseases, 6 (3.2%) patients experienced aborted sudden cardiac death, 3 (1.6%) cerebral ischemic strokes, 11 (6%) recurrent myocardial ischemia and 6 (3.2%) acute heart failure. At univariate analysis a corrected QT interval peak of at least 480 ms relates to cardiovascular death (P < 0.001), aborted sudden cardiac death (P = 0.037), cerebral ischemic stroke (P = 0.016) and recurrences of myocardial infarction (P = 0.032). Multivariate analysis confirms its role an independent predictor of cardiovascular death [odds ratio 6.38, 95% confidence interval (CI) 1.77-22.92, P = 0.004], together with an ejection fraction of 35% or less (odds ratio 4.20, 95% CI 1.24-14.16, P = 0.021). The presence of either corrected QT of at least 480 ms or ejection fraction of 35% or less increases the sensitivity and the accuracy to correctly predict cardiovascular death without a significant reduction in specificity (sensitivity 88%, specificity 69%, accuracy 88%, area under curve 0.83, 95% CI 0.72-0.94, P < 0.01). CONCLUSION: A corrected QT interval peak of at least 480 ms in the acute phase of ST-elevation myocardial infarction is an independent predictor of cardiovascular death. Its association with reduced ejection fraction (<=35%) increases risk stratification accuracy. PMID- 26556441 TI - Clinical recommendations on Cardiac-CT in 2015: a position paper of the Working Group on Cardiac-CT and Nuclear Cardiology of the Italian Society of Cardiology. AB - We worked out a position paper on cardiac-computed tomography (CCT) endorsed by the Working Group on CCT and Nuclear Cardiology of the Italian Society of Cardiology. The CCT clinical indications were discussed and formulated according to the following two modalities: a brief paragraph dedicated to each indication, with the description of clinical usefulness of different indications; and each indication was rated by the technical panel for appropriateness, using a score assessing whether the use of CCT for each indication is appropriate, uncertain, or inappropriate. All conventional CCT clinical indications, regarding coronary and noncoronary evaluation, were discussed and rated. Moreover, we wrote specific sections regarding the newest CCT applications, such as stress perfusion computed tomography, noninvasive evaluation of fractional flow reserve, and CCT use in athletes. The present study has the following two main objectives: because the diagnostic performance of coronary computed tomography angiography (CCTA) is strictly dependent on adequate technology and local expertise, we strove to provide clinical recommendations on CCTA that may help Italian physicians involved with this diagnostic tool; and to give an update on new indications of CCTA, such as its use for safely discharging patients with suspected acute coronary syndromes from the emergency department, and latest clinical results that have been made possible by the remarkable technology developments of the scanners. PMID- 26556443 TI - Do left atrial appendage morphology and function help predict thromboembolic risk in atrial fibrillation? AB - Clinical scores (i.e. CHA2DS2-VASc) are the mainstay of thromboembolic risk management in nonvalvular atrial fibrillation. Nonetheless, they bear some limitations to precisely define risk-benefit ratio of oral anticoagulation (OAC), both with vitamin K antagonists and with novel direct oral anticoagulants, especially in patients with low-intermediate scores. Cardiovascular imaging, allowing directly visualization of those pathophysiological alterations, which may lead to the formation of intracardiac thrombi, offers itself as a unique tool helping to refine thromboembolic risk stratification. Many parameters have been tested, focusing primarily on functional and morphological variables of the left atrium and left atrial appendage (LAA). Left atrium volume and LAA peak flow velocity have, for a longtime, been associated with increased thromboembolic risk, whereas some new parameters, such as left atrium fibrosis assessed by late gadolinium enhanced (LGE) MRI, left atrium and LAA strain and LAA morphology have more recently shown some ability in predicting embolic events in atrial fibrillation patients. Overall, however, these parameters have seen, to date, scarce clinical implementation, especially because of the inconsistency of validated cutoffs and/or strong clinical evidence driven by technical limitations, such as expensiveness of the technologies (i.e. MRI or computed tomography), invasiveness (i.e. transesophageal echocardiography) or limited reproducibility (i.e. LGE MRI). In conclusion, to date, cardiovascular imaging plays a limited role; however, validation and diffusion of the new techniques hereby systematically presented hold the potential to refine thromboembolic risk stratification in nonvalvular atrial fibrillation. PMID- 26556442 TI - Cardiac surgery with extracorporeal circulation and concomitant malignancy: early and long-term results. AB - AIMS: We retrospectively evaluated early and long-term results of cardiac surgery using extracorporeal circulation (ECC) in patients affected by malignancies and the potential influence of ECC on malignancy progression during follow-up. METHODS: Out of 7078 patients referred for cardiac surgery from January 2001 to December 2012, 241 consecutive patients (3.4%) (mean age 72 +/- 8 years; men 170) had malignancy either known before or detected during hospital stay. Organ malignancies were present in 201 patients (83%) and hematological malignancies in 40 (17%). Early stages of cancer (I-II, in remission) were present in 180 (75%) patients, and advanced stages (III-IV for organ malignancies , multiple organ involvement for hematological malignancies) in 61 (25%). EuroSCORE I and II were 8.6 +/- 5.4 and 3.8 +/- 2.1%, respectively. Cardiac surgery with ECC consisted in isolated (n = 176) or multiple procedures (n = 65). Follow-up (mean 57 +/- 40 months) was 99% complete. RESULTS: In-hospital mortality was 5.8% (n = 14); 1.67% (n = 4) died from cancer-related causes. Ten-year survival was 65 +/- 5%, and freedom from cardiac death was 92 +/- 3.5%. Freedom from cancer-related death was 90 +/- 3% for patients operated on in early stages of cancer compared with 60 +/- 8.4% for those who operated on in advanced stages (P < 0.0001), and 89 +/- 2.6% for organ malignancies compared with 48 +/- 13% for hematological malignancies (P = 0.0002); hematological malignancies different from Hodgkin/non-Hodgkin lymphoma affected long-term survival (P < 0.05). Progression of malignancy was observed in 29 patients (12.8%) at 18 +/- 10 months. CONCLUSION: Cardiac surgery in cancer patients is not associated with increased in-hospital mortality and provides satisfactory freedom from cardiac death. Long-term survival in early stages of cancer appears satisfactory. Time interval between ECC and progression of malignancy during follow-up should apparently exclude a close relationship of ECC on cancer progression. Hematological malignancies seem to have a negative impact on the overall outcome. PMID- 26556444 TI - Paradoxical low-flow aortic stenosis is defined by increased ventricular hydraulic load and reduced longitudinal strain. AB - AIMS: Patients with paradoxical low-flow severe aortic stenosis (PLF-AS) reportedly have higher left ventricular hydraulic load and more systolic strain dysfunction than patients with normal-flow aortic stenosis. This study investigates the relationship of systolic loading and strain to PLF-AS to further define its pathophysiology. METHODS: One hundred and twenty patients (age 79 +/- 12 years, 37% men) with an indexed aortic valve area (AVAi) of 0.6 cm/m or less and an ejection fraction of 50% or higher were divided into two groups based on indexed stroke volume (SVi): PLF-AS, SVi <= 35 ml/m, N = 46; normal-flow aortic stenosis, SVi > 35 ml/m, N = 74). Valvular and arterial load were assessed using multiple measurements, and strain was assessed using speckle-tracking echocardiography. RESULTS: Patients with PLF-AS were found to have more valvular load (lower AVAi, P = 0.028; lower energy loss coefficient, P = 0.001), more arterial load [decreased arterial compliance and increased systemic vascular resistance (SVR), both P < 0.001] and more total hydraulic load [increased valvuloarterial impedance (Zva), P < 0.001]. Transvalvular gradients and arterial pressures were similar. Longitudinal strain was lower in PLF-AS (P < 0.001), but circumferential and rotation strains were similar. On adjusted regression, AVAi, SVR and longitudinal strain were associated with PLF-AS [odds ratio (OR) = 1.34, P = 0.043; OR = 1.31, P = 0.004; OR = 1.34, P = 0.011, respectively]. When SVR and AVAi were replaced with Zva, longitudinal strain and Zva (OR = 1.38, P = 0.015; OR = 1.33, P < 0.001 for both, respectively) were associated with PLF-AS. CONCLUSION: Increased hydraulic load, from more severe valvular stenosis and increased vascular resistance, and longitudinal strain impairment are associated with PLF-AS and their interplay is likely fundamental to its pathophysiology. PMID- 26556445 TI - A life-threatening presentation of eosinophilic granulomatosis with polyangiitis. AB - : Necrotizing eosinophilic myocarditis (NEM) is a life-threatening condition that needs rapid diagnosis by endomyocardial biopsy and hemodynamic support usually by mechanical circulatory systems. We present the case of a 25-year-old Caucasian man who developed a refractory cardiogenic shock due to a NEM that was supported with a peripheral veno-arterial extracorporeal membrane oxygenation associated with intravenous steroids and recovered after 2 weeks. Further instrumental investigations lead to the final diagnosis of NEM as first presentation of eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), remarking the importance of identifying the systemic disorder that usually triggers the eosinophilic damage of the myocardium. PMID- 26556446 TI - Trans-catheter mitral valve implantation for mitral regurgitation: clinical case description and literature review. AB - Trans-catheter mitral valve implantation (TMVI) is actually the most attractive technique for treating patients with severe mitral regurgitation, who are denied surgical therapy. Recently, trans-catheter implantation of aortic biological prosthesis in mitral position has been done in compassionate cases, and very few experiences of TMVI in native non-calcified valves have been recently reported in very-high-risk patients, mainly with functional mitral regurgitation.Here, we report our case of TMVI using the second-generation CardiAQ prostheisis (CardiAQ Valve Technologies, Irvine, California, USA), reviewing the current state of the art. PMID- 26556449 TI - [Not Available]. PMID- 26556448 TI - Transcatheter occlusion of left atrial appendage with persistent thrombus using a trans-radial embolic protection device. AB - : The image describes a case of left atrial appendage occlusion in a patient with atrial fibrillation, previous haemorrhagic stroke, and left atrial appendage thrombosis. A cerebral vascular filter was used during the device implantation. The use of cerebral embolic protection device can increase the safety of left atrial appendage occlusion, in selected high-risk patients. PMID- 26556450 TI - [Compatibility of intravenous medications needs attention. Catheter occlusion, treatment failure and embolisms can be prevented]. AB - When dealing with more drugs than available lumens, intravenous medications need to be co-administered in the same catheter. This type of scenario may induce therapeutic risks, such as catheter occlusion, changes in drug effect or embolization of precipitated particles. Various sources are available to provide information on compatibilities of intravenous medications. When using these sources, the applicability of the information must be assessed, comparing concentrations, diluents used and other pharmaceutical aspects. For the last three years, a group of pharmacists at Sahlgrenska University Hospital has worked on a project collecting and validating compatibility data for intravenous medications. In the future, this data will be available to more hospitals in Sweden. PMID- 26556451 TI - [Slow-healing ulcers on the feet can be skin tumors--two cases described]. PMID- 26556452 TI - [The point of being wise when the world is insane. The great betrayal]. PMID- 26556453 TI - [Not Available]. PMID- 26556454 TI - [Not Available]. PMID- 26556455 TI - [The Swedish Society of Medicine: Ethics and jurisprudence concerning life sustaining treatment is clear]. PMID- 26556456 TI - [The Swedish National Board of Health and Welfare on life-sustaining treatment: The decision always lies with the physician]. PMID- 26556457 TI - [Suicide figures among young are high based on zero vision]. PMID- 26556458 TI - [Reduced risk of suicide with SSRIs a medical triumph]. PMID- 26556459 TI - ["First line" new early intervention for young people's mental health]. PMID- 26556460 TI - [Not Available]. PMID- 26556461 TI - Triticeous Cartilage CT Imaging Characteristics, Prevalence, Extent, and Distribution of Ossification. AB - OBJECTIVE: The triticeous cartilage is a small ovoid cartilaginous structure variably present as a component of the laryngeal skeleton. This structure has received scant attention in the literature and has yet to be described adequately on cross-sectional imaging. STUDY DESIGN AND SETTING: Retrospective study in a tertiary medical center. SUBJECTS AND METHODS: We investigated triticeous cartilage prevalence in a large population utilizing computed tomography images. The cases of all patients with computed tomography angiography images of the neck from October 1, 2013, to September 31, 2014, were examined. A total of 663 patients were included in this study (age: range, 18-97 years; mean +/- SD, 65 +/ 15 years), 58.4% men and 41.6% women. The presence of a triticeal cartilage and its site, number, and degree of ossification were recorded. RESULTS: A total of 53.1% of patients had at least 1 triticeous cartilage (352 of 663). Prevalence was 57.4% (222 of 387) among men and 47.1% (130 of 276) among women. The presence of bilateral triticeous cartilages was more common than unilateral (63.1%, 222 of 352). A minority of patients (4.5%, 16 of 352) had a cartilaginous triticeous with no appreciable ossification, and more than half (54.0%, 190 of 352) had mild triticeal ossification. Moderate ossification was found in 34.9% of patients (123 of 352) and marked ossification in 6.5% (23 of 352). CONCLUSION: The presence of a triticeous cartilage is common and of variable appearance. As the clinical and surgical significance of this anatomic structure may be misinterpreted, it is important for imaging interpreters to be familiar with this seldom-recognized anatomic structure and recognize its variable appearance on cross-sectional imaging to avoid a misdiagnosis. PMID- 26556462 TI - Short-term Quality-of-Life Outcomes following Transoral Diverticulotomy for Zenker's Diverticulum: A Prospective Single-Group Study. AB - OBJECTIVE: To prospectively analyze quality-of-life outcomes following transoral diverticulotomy with cricopharyngeal myotomy (DCPM) for Zenker's diverticulum (ZD). STUDY DESIGN: Prospective single-group study. SETTINGS: Tertiary academic institution. SUBJECTS AND METHODS: A prospective multicenter study performed from January 1, 2012, to July 1, 2014, included 18 patients presenting with ZD undergoing DCPM. Standardized questionnaires-including the 10-item Eating Assessment Tool (EAT-10), Functional Outcome of Swallowing Scale (FOSS), and the Reflux Symptom Index (RSI)-were completed preoperatively and at 3 and 6 months postoperatively. Videofluoroscopic studies were obtained and analyzed by our senior speech-language pathologist, who was blinded to the clinical outcomes. RESULTS: Eighteen patients were included (11 women; mean age, 72.6 years; range, 53-86 years). All patients had ZD on preoperative videofluoroscopic swallowing studies. The most common comorbidities included hypertension (10 of 18, 55.6%), dyslipidemia (8 of 18, 44.4%), hiatal hernia (6 of 18, 33.3%), and gastroesophageal reflux disease (5 of 18, 27.8%). Median preoperative RSI was 27 (interquartile range [IQR], 22.5-31.5); FOSS, 2 (IQR, 2-3); and EAT-10, 21.5 (IQR, 13.5-27.5). The 3-month questionnaire (88.9% completion) demonstrated an improved median RSI of 5 (IQR, 1-7.5; P < .001), FOSS of 0 (IQR, 0; P < .001), and EAT-10 of 0 (IQR, 0-3; P < .001). Fourteen patients (77.8%) completed the 6 month questionnaire, demonstrating a median RSI of 4 (IQR, 0-8), FOSS of 0 (IQR, 0-0.5), and EAT-10 of 1 (IQR, 0-3). While regurgitation decreased following surgery (P = .007), nighttime cough did not (P = .25). CONCLUSION: This study supports an improvement in functional outcome and quality of life in patients with ZD undergoing DCPM. PMID- 26556463 TI - Potential Benefits of Combination Therapy as Primary Treatment for Sudden Sensorineural Hearing Loss. AB - OBJECTIVE: We analyzed the effectiveness of combination therapy (CT) for idiopathic sudden sensorineural hearing loss (ISSNHL) and the utility of intratympanic dexamethasone injection (ITDI) reapplication as salvage treatment for ISSNHL refractory to CT. STUDY DESIGN: Case series with chart review. SETTING: Academic university hospital. SUBJECTS AND METHODS: We reviewed 229 patients with ISSNHL and divided these patients into 2 groups according to treatment: systemic steroid therapy (SST) and CT groups. The SST group received prednisolone therapy. The CT group also received ITDI daily. Patients who demonstrated no recovery (<10 dB) after initial treatment were defined as refractory and received salvage ITDI therapy: ITDI reapplication in the CT group and ITDI application in the SST group. RESULTS: Hearing recovery rates were 77.8% (77/99) in the CT group and 60.8% (79/130) in the SST group. The difference was statistically significant (P = .011). Initial pure-tone audiometry and vertigo were affective factors on hearing recovery rates in the CT group. After salvage therapy, hearing improvement of 10 dB or greater was noted in 6 of the 22 (27.3%) patients in the CT group and 16 of the 51 (31.4%) patients in the SST group. The difference in efficacy of salvage therapy between the CT and SST groups was simply not significant (P = .612). CONCLUSIONS: Combination therapy was more effective for ISSNHL in achieving hearing gain than SST alone. Furthermore, ITDI reapplication for ISSNHL refractory to CT was as effective as salvage ITDI for ISSNHL refractory to SST. PMID- 26556464 TI - Amblyaudia: Review of Pathophysiology, Clinical Presentation, and Treatment of a New Diagnosis. AB - OBJECTIVE: Similar to amblyopia in the visual system, "amblyaudia" is a term used to describe persistent hearing difficulty experienced by individuals with a history of asymmetric hearing loss (AHL) during a critical window of brain development. Few clinical reports have described this phenomenon and its consequent effects on central auditory processing. We aim to (1) define the concept of amblyaudia and (2) review contemporary research on its pathophysiology and emerging clinical relevance. DATA SOURCES: PubMed, Embase, and Cochrane databases. REVIEW METHODS: A systematic literature search was performed with combinations of search terms: "amblyaudia," "conductive hearing loss," "sensorineural hearing loss," "asymmetric," "pediatric," "auditory deprivation," and "auditory development." Relevant articles were considered for inclusion, including basic and clinical studies, case series, and major reviews. CONCLUSIONS: During critical periods of infant brain development, imbalanced auditory input associated with AHL may lead to abnormalities in binaural processing. Patients with amblyaudia can demonstrate long-term deficits in auditory perception even with correction or resolution of AHL. The greatest impact is in sound localization and hearing in noisy environments, both of which rely on bilateral auditory cues. Diagnosis and quantification of amblyaudia remain controversial and poorly defined. Prevention of amblyaudia may be possible through early identification and timely management of reversible causes of AHL. IMPLICATIONS FOR PRACTICE: Otolaryngologists, audiologists, and pediatricians should be aware of emerging data supporting amblyaudia as a diagnostic entity and be cognizant of the potential for lasting consequences of AHL. Prevention of long term auditory deficits may be possible through rapid identification and correction. PMID- 26556465 TI - Quality Improvement in Otolaryngology Residency: Survey of Program Directors. AB - OBJECTIVES: The Clinical Learning Environment Review focuses on the responsibility of the sponsoring institution for quality and patient safety. Very little information is known regarding the status of quality improvement (QI) education during otolaryngology training. The purpose of this survey is to evaluate the extent of resident and faculty participation in QI and identify opportunities for both resident curriculum and faculty development. STUDY DESIGN: Cross-sectional survey SUBJECTS AND METHODS: A 15-item survey was distributed to all 106 otolaryngology program directors. The survey was developed after an informal review of the literature regarding education in QI and patient safety. Questions were directed at the format and content of the QI curriculum, as well as barriers to implementation. RESULTS: There was a 39% response rate. Ninety percent of responding program directors considered education in QI important or very important to a resident's future success. Only 23% of responding programs contained an educational curriculum in QI, and only 33% monitored residents' individual outcome measures. Barriers to implementation of a QI program included inadequate number of faculty with expertise in QI (75%) and competing resident educational demands (90%). Every program director considered morbidity and mortality conferences as an integral component in QI education. CONCLUSIONS: Program directors recognize the importance of QI in otolaryngology practice. Unfortunately, this survey identifies a distinct lack of resources in support of these educational goals. The results highlight the need to generate a comprehensive and stepwise approach to QI for faculty development and resident instruction. PMID- 26556466 TI - Author Self-Citation in the Otolaryngology Literature: A Pilot Study. AB - OBJECTIVE: To determine the prevalence of author self-citation in the field of otolaryngology. STUDY DESIGN AND SETTING: A retrospective review of bibliographic references in 5 otolaryngology journals. SUBJECTS AND METHODS: Five high-impact otolaryngology journals were reviewed over a 3-month period between January and March 2014 to identify the pattern of author self-citations. Data included study type, otolaryngology topic, authorship, total citations, author self-citations, and country of origin. RESULTS: Nearly two-thirds of articles contained at least 1 self-citation, with an average of 2.6 self-citations per article. Self citations represented nearly 10% of total citations. Articles with at least 1 self-citation had more authors (5.8 vs 4.9, P < .01) and more citations (30.4 vs 22.2, P < .01) per article than did those without self-citations. There was no difference in self-citation practices between articles originating within the United States and abroad (P = .65). Last authors were the most frequent self citers and were more likely than lead authors to cite themselves (P < .01). Original reports contained the highest percentage of self-citations per article as compared with reviews and case reports (P < .01). CONCLUSION: Author self citation in the otolaryngology literature is common and compares similarly to other medical specialties previously studied. Self-citation should not be considered inappropriate, as it is often done to expand on earlier research. Nevertheless, editors, researchers, and readers should be aware of this increasingly recognized phenomenon and its associated potential implications to the process of scientific inquiry. PMID- 26556467 TI - Influence of aripiprazole once monthly on clinical symptoms and cognitive function in two schizophrenia patients: Preliminary results. PMID- 26556468 TI - Phosphorus Flow Patterns in the Chaohu Watershed from 1978 to 2012. AB - Understanding historical patterns of phosphorus (P) cycling is critical for sustainable P management and eutrophication mitigation in watersheds. This study built a bottom-up model using the substance flow analysis approach to quantify P cycling in the Chaohu watershed during 1978-2012. We found that P flows have been intensified, with a 5-fold increase of annual P inputs to sustain the expanding intensive agriculture. Annually, most P inputs (75%) were stored within the watershed, which caused accelerating buildup of legacy P in cultivated land (from 4.9 Gg to 6.5 * 10(2) Gg), uncultivated land (from 2.1 Gg to 1.3 * 10(2) Gg) and surface water (from 3.7 Gg to 2.6 * 10(2) Gg) during 1978-2012. The main legacy P sources include fertilizer application for cultivated land, phosphogypsum abandonment for uncultivated land, respectively. The animal husbandry contributed about 63-66% of total P inputs to surface water. The contribution of animal food P increased greatly during 1978-2012, from 7% to 24% and from 1% to 8% for urban and rural residents, respectively. This work demonstrates principle for the buildup of legacy P at the watershed-scale, and advances the knowledge of sustainable P management, such as improving agricultural technologies to reduce fertilizer application. PMID- 26556469 TI - The objective measurement of physical activity and sedentary behaviour in 2-3 year olds and their parents: a cross-sectional feasibility study in the bi-ethnic Born in Bradford cohort. AB - BACKGROUND: The reported lower physical activity (PA) levels of British South Asians (SA) are suggested as a key influence in their increased risk of non communicable diseases compared to their White British peers. Differences in objectively measured PA and sedentary behaviour (SB) between these ethnic groups have been observed during childhood (ages: 8-10 years). However, no information exists on objectively measured PA/SB in younger children, or how early in life differences in these behaviours emerge. Assessing PA/SB in the Born in Bradford (BIB) cohort study provides an opportunity to address such gaps in the literature, but previous studies have found recruiting and retaining SA participants challenging, and the feasibility of using accelerometers with SA children and parents is unknown. This study investigated the feasibility of recruiting and objectively measuring the habitual PA/SB of 2-3 year old SA and White British children and parents from the BIB study. METHODS: Families were informed about the study during routine BIB assessments. Consenting families were visited at home for anthropometry measurements, interviews, material delivery and collection. Participants (child and parents) were instructed to wear the ActiGraph GT3X+ for 8 days. Descriptive statistics were computed, and ethnic differences tested (Chi-square) for recruitment uptake and compliance. RESULTS: 160 families (30 % SA) provided contact details, and 97 (22 % SA) agreed to enter the study. White British families showed lower refusal and higher intake into the study than SA (p = 0.006). Of 89 children issued with an accelerometer, 34 % complied with the 8-day protocol (significantly less SA; p = 0.015) and 75 % provided enough days (>= 3) to assess habitual PA/SB (no ethnic differences). Parental rates of compliance with the protocol did not differ between ethnicities. Issues experienced with the protocol and accelerometer use, and successful implementation strategies/procedures are presented. CONCLUSIONS: Although greater efforts may be required to recruit SA, those consenting to participate were as likely as White British to provide enough data to assess habitual PA/SB. The issues and successful strategies reported in this feasibility study represent valuable information for planning future studies, and enhance recruitment and compliance with accelerometer protocols in SA and White British toddlers and parents. PMID- 26556470 TI - Applicability of gene expression and systems biology to develop pharmacogenetic predictors; antipsychotic-induced extrapyramidal symptoms as an example. AB - Pharmacogenetics has been driven by a candidate gene approach. The disadvantage of this approach is that is limited by our current understanding of the mechanisms by which drugs act. Gene expression could help to elucidate the molecular signatures of antipsychotic treatments searching for dysregulated molecular pathways and the relationships between gene products, especially protein-protein interactions. To embrace the complexity of drug response, machine learning methods could help to identify gene-gene interactions and develop pharmacogenetic predictors of drug response. The present review summarizes the applicability of the topics presented here (gene expression, network analysis and gene-gene interactions) in pharmacogenetics. In order to achieve this, we present an example of identifying genetic predictors of extrapyramidal symptoms induced by antipsychotic. PMID- 26556471 TI - Aptamer/Polydopamine Nanospheres Nanocomplex for in Situ Molecular Sensing in Living Cells. AB - A nanocomplex was developed for molecular sensing in living cells, based on the fluorophore-labeled aptamer and the polydopamine nanospheres (PDANS). Due to the interaction between ssDNA and PDANS, the aptamer was adsorbed onto the surface of PDANS forming the aptamer/PDANS nanocomplex, and the fluorescence was quenched by PDANS through Forster resonance energy transfer (FRET). In vitro assay, the introduction of adenosine triphosphate (ATP) led to the dissociation of the aptamer from the PDANS and the recovery of the fluorescence. The retained fluorescence of the nanocomplex was found to be linear with the concentration of ATP in the range of 0.01-2 mM, and the nanocomplex was highly selective toward ATP. For the strong protecting capability to nucleic acids from enzymatic cleavage and the excellent biocompatibility of PDANS, the nanocomplex was transported into cells and successfully realized "signal on" sensing of ATP in living cells; moreover, the nanocomplex could be employed for ATP semiquantification. This design provides a strategy to develop biosensors based on the polydopamine nanomaterials for intracellular molecules analysis. For the advantages of polydopamine, it would be an excellent candidate for many biological applications, such as gene and drug delivery, intracellular imaging, and in vivo monitoring. PMID- 26556472 TI - Circumscribed juvenile pityriasis rubra pilaris responsive to alitretinoin. PMID- 26556473 TI - Atmospheric Solid Analysis Probe-Ion Mobility Mass Spectrometry: An Original Approach to Characterize Grafting on Cyclic Olefin Copolymer Surfaces. AB - A cyclic olefin copolymer (COC) was grafted with aryl layers from aryldiazonium salts, and then we combined infrared spectrometry, atomic force microscopy (AFM), and ion mobility mass spectrometry with atmospheric solid analysis probe ionization (ASAP-IM-MS) to characterize the aryl layers. ASAP is a recent atmospheric ionization method dedicated to the direct analysis of solid samples. We demonstrated that ASAP-IM-MS is complementary to other techniques for characterizing bromine and sulfur derivatives of COC on surfaces. ASAP-IM-MS was useful for optimizing experimental grafting conditions and to elucidate hypotheses around aryl layer formation during the grafting process. Thus, ASAP-IM MS is a good candidate tool to characterize covalent grafting on COC surfaces. PMID- 26556474 TI - Narrative Length and Speech Rate in Battered Women. AB - Narrative length and speech rate of traumatic recollections have been previously associated with different emotions and adjustment trajectories after trauma. However, the evidence is limited and the results are mixed. The present study aimed to evaluate length (i.e., word count) and speech rate (i.e., words per minute) in narratives of events with different valence (i.e., neutral, positive, and negative/traumatic) by 50 battered women (trauma group) and 50 non traumatized women (controls). The results showed that traumatic narratives by the trauma group were longer than those by the control group. Moreover, they were inversely related to time since the event and anxiety during disclosure, whereas the speech rate was also inversely associated with anxiety, as well as with peritraumatic dissociation and avoidance. The shorter narratives for positive events and a decelerated speech pattern for traumatic experiences predicted psychological symptoms. Additionally, the individual's emotional state predicted narrative aspects, with bidirectional effects. Our findings showed that linguistic characteristics of traumatic narratives (but also of narratives of positive events) revealed information about how the victims elaborated autobiographical memories and coped with the trauma. PMID- 26556475 TI - Primary Hepatic Gastrinoma. PMID- 26556476 TI - Use of Preoperative Magnetic Resonance Imaging to Select Patients with Rectal Cancer for Neoadjuvant Chemoradiation--Interim Analysis of the German OCUM Trial (NCT01325649). AB - INTRODUCTION: Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR. METHODS: Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup. RESULTS: TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR. CONCLUSIONS: Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients. PMID- 26556478 TI - How Much Do Metamemory Beliefs Contribute to the Font-Size Effect in Judgments of Learning? AB - Evidence shows that the font size of study items significantly influences judgments of learning (JOLs) and that people's JOLs are generally higher for larger words than for smaller words. Previous studies have suggested that font size influences JOLs in a belief-based way. However, few studies have directly examined how much people's beliefs contribute to the font-size effect in JOLs. This study investigated the degree to which font size influenced JOLs in a belief based way. In Experiment 1, one group of participants (learners) studied words with different font sizes and made JOLs, whereas another group of participants (observers) viewed the learners' study phase and made JOLs for the learners. In Experiment 2, participants made both JOLs and belief-based recall predictions for large and small words. Our results suggest that metamemory beliefs play an important role in the font-size effect in JOLs. PMID- 26556477 TI - Prediction of impending preterm delivery based on sonographic cervical length and different cytokine levels in cervicovaginal fluid in preterm labor. AB - AIMS: The aim of this study was to determine whether cervicovaginal interleukin (IL)-1beta, IL-6 and IL-8 levels, and cervical length, alone or in combination, could predict impending preterm delivery in women with preterm labor and intact membranes. MATERIAL AND METHODS: Cervicovaginal swab samples for IL-1beta, IL-6, and IL-8 assays were taken from 136 consecutive women with preterm labor (23-34 weeks) before the transvaginal ultrasonography examination to measure cervical length. The primary outcome measurement was spontaneous preterm delivery within 7 days of sampling. RESULTS: Spontaneous preterm delivery within 7 days occurred in 28.6% (39/136) of patients. Receiver-operator characteristic (ROC) curves indicated that cervical length (P < 0.001), cervicovaginal IL-6 (P < 0.001) and IL-8 (P = 0.014), but not IL-1beta, could predict delivery within 7 days. According to the logistic regression analysis, high cervicovaginal IL-8 (P = 0.008) and IL-6 (P = 0.038) levels and short cervical length (P < 0.001) were significantly associated with delivery within 7 days, even after controlling for baseline variables. A combination of cervix length and cervicovaginal IL-8 increased the specificity of detecting delivery within 7 days to 92.8%, which was superior to either test alone (P < 0.001), but the sensitivity was only 56.4%. CONCLUSION: In women with preterm labor, among the parameters assessed, cervicovaginal IL-6 and IL-8 and cervical length are the most important parameters in predicting impending preterm delivery. A combination of cervix length and cervicovaginal IL-8 appeared to be the best for predicting impending preterm delivery, but the relatively low sensitivity of this test may limit its clinical usefulness. PMID- 26556480 TI - Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia. AB - Most non-long terminal repeat (non-LTR) retrotransposons encoding a restriction like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an "archaeal" RNase H domain upstream of reverse transcriptase (RT), which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes. PMID- 26556481 TI - Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study. AB - Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99+/ 9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients. PMID- 26556479 TI - Retinoic Acid Ameliorates Pancreatic Fibrosis and Inhibits the Activation of Pancreatic Stellate Cells in Mice with Experimental Chronic Pancreatitis via Suppressing the Wnt/beta-Catenin Signaling Pathway. AB - Pancreatic fibrosis, a prominent feature of chronic pancreatitis (CP), induces persistent and permanent damage in the pancreas. Pancreatic stellate cells (PSCs) provide a major source of extracellular matrix (ECM) deposition during pancreatic injury, and persistent activation of PSCs plays a vital role in the progression of pancreatic fibrosis. Retinoic acid (RA), a retinoid, has a broad range of biological functions, including regulation of cell differentiation and proliferation, attenuating progressive fibrosis of multiple organs. In the present study, we investigated the effects of RA on fibrosis in experimental CP and cultured PSCs. CP was induced in mice by repetitive cerulein injection in vivo, and mouse PSCs were isolated and activated in vitro. Suppression of pancreatic fibrosis upon administration of RA was confirmed based on reduction of histological damage, alpha-smooth muscle actin (alpha-SMA) expression and mRNA levels of beta-catenin, platelet-derived growth factor (PDGF)-Rbeta transforming growth factor (TGF)-betaRII and collagen 1alpha1 in vivo. Wnt 2 and beta-catenin protein levels were markedly down-regulated, while Axin 2 expression level was up regulated in the presence of RA, both in vivo and in vitro. Nuclear translation of beta-catenin was significantly decreased following RA treatment, compared with cerulein-induced CP in mice and activated PSCs. Furthermore, RA induced significant PSC apoptosis, inhibited proliferation, suppressed TCF/LEF-dependent transcriptional activity and ECM production of PSC via down-regulation of TGFbetaRII, PDGFRbeta and collagen 1alpha1 in vitro. These results indicate a critical role of the Wnt/beta-catenin signaling pathway in RA-induced effects on CP and PSC regulation and support the potential of RA as a suppressor of pancreatic fibrosis in mice. PMID- 26556482 TI - Persistence and concomitant medication in patients with overactive bladder treated with antimuscarinic agents in primary care. An observational baseline study. AB - OBJECTIVE: To assess therapeutic persistence and its relationship with concomitant medication in patients treated with fesoterodine versus tolterodine and solifenacin for overactive bladder (OAB) in standard clinical practice conditions. MATERIAL AND METHODS: An observational, multicentre retrospective study was performed based on medical registries of patients followed-up in primary care (PC). Three study groups were analysed. Persistence was defined as the time (in months) without withdrawing from the initial therapy or without changing to another medication for at least 30 days after the initial prescription. The concomitant medications were antidepressants, anxiolytic/hypnotic agents, antibiotics, antiseptic agents, laxatives and skin products. We employed the SPSSWIN program version 17 (statistical significance, P<.05). RESULTS: We selected 3094 patients for the study. The median age was 54.0 years and 62.2% were women. The patients treated with fesoterodine shown greater treatment persistence (12 months) when compared with those who took solifenacin and tolterodine (40.2% vs. 34.7% and 33.6%, respectively; P=.008). They also showed a lower use of concomitant medication (1.1 vs. 1.2 and 1.2 drugs, respectively; percentages: 61.6% vs. 67.1% and 70.1%, respectively; P<.03). CONCLUSIONS: The patients undergoing OAB treatment with fesoterodine, when compared with those taking solifenacin and tolterodine, were associated with greater treatment persistence and a reduced use of concomitant medication. PMID- 26556483 TI - Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta Analysis. AB - BACKGROUND AND AIM: Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed. METHODS: The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs) of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption. RESULTS: Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45-0.84). For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47 0.92). High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42-0.68). The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58-0.92). The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV) infection. CONCLUSION: Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis. PMID- 26556484 TI - Cessation of spread as a treatment objective in vitiligo: perception from the patients' point of view. PMID- 26556485 TI - Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. METHODS: We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar's test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. RESULTS: In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60-0.76), 0.73 (95% CI: 0.62-0.82), 2.57 (95% CI: 1.82-3.62), and 0.43 (95% CI: 0.34-0.54), 0.76 (95% CI: 0.72-0.80) and 6.01 (95% CI: 3.69-9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55-0.80), 0.88 (95% CI: 0.77-0.94), 5.80 (95% CI: 3.06-10.99), and 0.35 (95% CI: 0.24-0.51), 0.85 (95% CI: 0.82-0.88) and 16.50 (95% CI: 8.18-33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66-0.75), specificity of 0.79 (95% CI: 0.79-0.80), DOR of 6.92 (95% CI: 4.36-11.00), and AUC of 0.78 (95% CI: 0.72-0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51-0.60), specificity of 0.79 (95% CI: 0.76-0.82), DOR of 6.88 (95% CI: 2.30-20.60), and AUC of 0.77 (95% CI: 0.73-0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52-0.83), specificity of 0.84 (95% CI: 0.68-0.93), DOR of 11.51 (95% CI: 6.14 21.56), and AUC of 0.83 (95% CI: 0.80-0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72-0.85), specificity of 0.89 (95% CI: 0.85-0.93), DOR of 24.64 (95% CI: 6.95 87.37), and AUC of 0.87 (95% CI: 0.81-0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38-0.54), specificity of 0.93 (95% CI: 0.91-0.95), DOR of 19.86 (95% CI: 0.86-456.91), and AUC of 0.86 (95% CI: 0.52-1.00). CONCLUSION: SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future. PMID- 26556486 TI - Higher intrinsic network excitability in ventral compared with the dorsal hippocampus is controlled less effectively by GABAB receptors. AB - BACKGROUND: Elucidating specializations of the intrinsic neuronal network between the dorsal and the ventral hippocampus is a recently emerging area of research that is expected to help us understand the mechanisms underlying large scale functional diversification along the hippocampus. The aim of this study was to characterize spontaneous network activity between the dorsal and the ventral hippocampus induced under conditions of partial or complete blockade of GABAergic inhibition (i.e. disinhibition). RESULTS: Using field recordings from the CA3 and CA1 fields of hippocampal slices from adult rats I found that ventral compared with dorsal hippocampus slices displayed higher propensity for and higher frequency of occurrence of spontaneous field potentials (spfps) at every level of disinhibition. Also NMDA receptor-depended spfps (spfps(-nmda)) occurred with higher probability more frequently and were larger in the ventral compared with the dorsal hippocampus. Importantly, blockade of GABA(B) receptors produced a stronger effect in enhancing the probability of generation of spfps and spfps( nmda) in the dorsal compared with the ventral hippocampal slices and increased spfps(-nmda) only in dorsal slices. CONCLUSION: These results demonstrate a higher intrinsic neuronal excitability of the ventral compared with the dorsal local circuitry with the considerable contribution of NMDA receptors. Furthermore, the GABA(B) receptors control the total and the NMDA receptor dependent excitation much less effectively in the ventral part of the hippocampus. It is proposed that NMDA and GABA(B) receptors significantly contribute to differentiate local network dynamics between the dorsal and the ventral hippocampus with important implications in the information processing performed along the long hippocampal axis. PMID- 26556487 TI - The effect of aortic stenosis on elderly hip fracture outcomes: A case control study. AB - INTRODUCTION: Aortic stenosis (AS) is an established predictor of perioperative complications following both cardiac and non-cardiac surgery. The purpose of this study was to evaluate the risk of mortality and perioperative complications among surgically treated hip fractures in elderly patients with moderate or severe AS compared to those without AS (negative controls). MATERIALS AND METHODS: A retrospective case-controlled review (1:2) of elderly (>=65 years) surgically treated hip fractures from 2011 to 2015 with moderate/severe AS (according to American Heart Association criteria) was conducted. Postoperative complication rates, 30 days and 1 year mortality were reviewed. RESULTS: Moderate/severe AS was identified in 65 hip fracture cases and compared to 129 negative controls. AS cases were significantly older with higher rates of coronary artery disease and atrial fibrillation (p<0.05). Rates of any 30-day perioperative complication (74% vs. 37%, p<0.001) and severe non-cardiac 30-day perioperative complication (52% vs. 26%, p=0.002) were significantly higher among AS cases compared to controls. Kaplan Meier estimates of 30-day mortality (14.7% vs. 4.2%, p<0.001) and 1-year mortality (46.8% vs. 14.1%, p<0.001) were significantly higher in AS cases compared to controls. Multivariate analysis of severe 30-day postoperative complications identified moderate/severe AS (OR 4.02, p=0.001), pulmonary disease (OR 7.36, p=0.002) and renal disease (OR 3.27, p=0.04) as independent predictors. Moderate/severe AS (OR 3.38, p=0.03), atrial fibrillation (OR 3.73, p=0.03) and renal disease (OR 4.44, p=0.02) were independent predictors of 30-day mortality. Moderate/severe AS (OR 5.79, p<0.001) and renal disease (OR 3.39, p=0.02) were independent predictors of 1-year mortality. CONCLUSION: Aortic stenosis is associated with a significantly increased risk of perioperative complications, 30 day mortality and 1-year mortality in elderly patients undergoing surgical treatment of hip fractures. PMID- 26556488 TI - Injured patients with very high blood alcohol concentrations. AB - OBJECTIVE: Most data regarding high blood alcohol concentrations (BAC) >=400 mg/dL have been from alcohol poisoning deaths. Few studies have described this group and reported their alcohol consumption patterns or outcomes compared to other trauma patients. We hypothesised trauma patients with very high BACs arrived to the trauma centre with less severe injuries than their sober counterparts. METHOD: Historical cohort of 46,222 patients admitted to a major trauma centre between January 1, 2002 and October 31, 2011. BAC was categorised into ordinal groups by 100 mg/dL intervals. Alcohol questionnaire data on frequency and quantity was captured in the BAC >=400 mg/dL group. The primary analysis was for BAC >=400 mg/dL. RESULTS: BAC was recorded in 44,502 (96.3%) patients. Those with a BAC >=400 mg/dL accounted for 1.1% (147) of BAC positive cases. These patients had the lowest proportion of severe trauma and in-hospital death in comparison with the other alcohol groups (p<0.001). In adjusted analysis, the risk for severe injury increased with the BAC groups between 1 and 199 mg/dL and was not different or decreased for groups above 200 mg/dL in reference to the BAC negative group (test for trend p=0.001). BAC >=400 group encountered more injuries caused by blunt trauma in comparison with the other alcohol groups (p<0.001), and the group comprised mainly of falls. Admission Glasgow Coma Scale was a poor predictor for traumatic brain injury in the high BAC group. Readmission occurred in 22.4% (33) of patients the BAC >=400 group. The majority of these patients reported drinking alcohol 4 or more days per week (81, 67.5%) and five or more drinks per day (79, 65.8%), evident of risky alcohol use. CONCLUSIONS: Most traumas admitted with BAC >=400 mg/dL survived and their injuries were less severe than their less intoxicated and sober counterparts. They also had evidence for risky alcohol use and nearly one-quarter returned to the trauma centre with another injury over the study period. Recognition of this highest BAC group presents an opportunity to provide focused care for their risky alcohol use. PMID- 26556490 TI - Correction: MRPack: Multi-Algorithm Execution Using Compute-Intensive Approach in MapReduce. PMID- 26556489 TI - [Pathophysiology of implant-associated infections: From biofilm to osteolysis and septic loosening]. AB - Biofilm formation is the key factor in the pathogenesis of implant-associated infections. The most common pathogens isolated are Staphylococcus species, opportunists belonging to the physiological flora of the skin. Biofilm formation starts with the adhesion of bacteria and colonisation preferentially occurs on the surfaces of the foreign body material. As an interactive symbiotic "city of microbes," biofilm formation represents an efficient survival strategy for bacteria. In clinically apparent infections the biofilm induces a local host response with infiltration of phagocytic immune cells. The proinflammatory microenvironment results in a stimulation of osteoclastogenesis, with local osteolysis, and finally septic loosening of the implant. According to the biofilm theory, retaining the implant in primary revision surgery is only recommended in early-stage infections with a stable implant; in late-stage infections, or when loosening occurs, the implant should be removed. Results of previous anti-biofilm therapies have not been satisfactory; therefore, current research is focused on prevention strategies, especially the modification of implant surfaces. Basic knowledge of the underlying pathophysiology is a prerequisite for the development of innovative interdisciplinary therapy and prevention strategies; in this context, essential aspects of biofilm formation, its consequences, and its relevance to diagnosis and therapy are described and discussed. PMID- 26556491 TI - [Peritonitis carcinomatosa from colorectal carcinoma: new treatment options]. AB - Peritonitis carcinomatosa occurs in 10% of patients with colorectal carcinoma. Compared with patients with lung and liver metastases, survival in patients with peritonitis carcinomatosa is worse if treated with systemic chemotherapy. However, treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) offers longer survival than systemic chemotherapy. A Dutch registration study shows that the 3- and 5-year survival of patients treated with cytoreductive surgery and HIPEC had a 3-year survival of 46% and a 5-year survival of 31%. Mortality and morbidity have dropped greatly due to standardisation of the intervention in accordance with the Dutch protocol. PMID- 26556492 TI - [Guideline thyroid cancer including diagnostics of the nodule]. AB - Thyroid cancer is comparatively rare. Thyroid nodules, on the other hand, are frequently diagnosed as a result of increasing use of diagnostic imaging. Cytological investigation of small nodules that have been found by chance often reveals micropapillary carcinoma that is probably not clinically relevant. The new guideline 'Thyroid cancer' advises that cytological investigation of these non-palpable, incidentally discovered thyroid nodules should only be performed on indication. The standard treatment for patients with papillary or follicular thyroid cancer consists of thyroidectomy followed by, if indicated, lymph-node dissection, ablation therapy with radioactive iodine and TSH-suppression. The extent of this treatment is determined on the basis of known prognostic factors and the results of initial treatment. Targeted systemic therapy is available for patients with metastatic progressive disease. There is more focus on the effects of short- and long-term treatment, in order to optimise quality of life. PMID- 26556493 TI - [Do not always puncture a thyroid nodule]. AB - The incidence of thyroid cancer is increasing, especially the papillary subtype. This increase can be mainly attributed to the detection of small - mostly indolent - papillary thyroid cancers as a consequence of the higher sensitivity of diagnostic techniques and the more frequent use of diagnostic applications. Two patients are described with (non-)palpable thyroid nodules to illustrate the risk of overdiagnostics and overtreatment. A thyroid incidentaloma detected on ultrasound, CT or MRI does not require further diagnostic procedures as standard. The pros and cons of diagnostic procedures must be discussed in a multidisciplinary team. PMID- 26556494 TI - [A man with an abnormality of the upper arm on an X-ray of the chest]. AB - A 82-year-old man was referred to our hospital because of a history of falling. Routine radiography of the chest accidentally showed an abnormality of the left upper arm. The x-ray showed calcifications - rings and arcs - also known as popcorn calcifications. This is a typical radiological sign which may indicate a tumour of the condroid matrix. PMID- 26556495 TI - [Not Available]. AB - The management of anticoagulation in patients undergoing invasive procedures is a complex clinical problem. Interrupting anticoagulation for a procedure increases the risk of thromboembolism. On the other hand, bridging anticoagulation with an alternative, short-acting anticoagulans increases the risk for peri-operative bleeding. A recent randomized controlled trial (the BRIDGE trial) shows that in patients with atrial fibrillation who had anticoagulant treatment interrupted for an elective invasive procedure, a strategy of forgoing bridging anticoagulation decreased the risk of major bleeding and was non-inferior to peri-operative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism. However, the study deserves comment. First, most of the patients were classified at low risk for thromboembolism, with a mean CHADS2-score of 2.3. Second, the majority of the procedures were low bleeding risk procedures. Whether bridging anticoagulation is helpful for patients with moderate to high-risk for thromboembolism undergoing high bleeding risk procedures remains unanswered. PMID- 26556497 TI - Monomeric Chiral and Achiral Basket-Handle Porphyrins: Synthesis, Structural Features, and Arrested Tautomerism. AB - Chiral and achiral basket-handle porphyrins (BHPs) with different p-xylene straps and peripheral solubilizing groups were synthesized using a previously established synthetic approach. Subsequent modification, functionalization, and metalation of the tetrapyrrolic macrocycle yielded more than 80 BHPs. The chiral representatives were resolved into their enantiomers, whose absolute configurations were determined by comparison of their ECD spectra with other experimental or quantum chemically calculated spectra. NMR studies and coupled cluster calculations proved that the free base BHPs, although highly symmetric, exhibited the phenomenon of "arrested tautomerism". Comparison of the solid-state structures of three metalated BHPs offered detailed insight into their three dimensional shape. Finally, directly linked dimeric porphyrins with a BHP subunit were synthesized from functionalized BHPs to prove their value as synthetic building blocks. PMID- 26556498 TI - Metreleptin Treatment in Patients with Non-HIV Associated Lipodystrophy. AB - Lipodystrophies are a heterogeneous group of disorders characterized by congenital or acquired loss of adipose tissue. Recently, metreleptin, a recombinant human leptin analog, has been approved for the treatment of patients with generalized lipodystrophy. Leptin is an adipokine which has a fundamental role in glucose and lipid homeostasis. Metreleptin treatment has been demonstrated to improve metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, increased hepatic fat content and elevated liver enzymes alanine transaminase and aspartate transaminase in patients with generalized lipodystrophy, and to correct hyperphagia that likely occurs as a result of leptin deficiency. Limited data has also suggested that metreleptin treatment might be beneficial on metabolic abnormalities in patients with partial lipodystrophy. This review focuses on potential benefits of metreleptin in various forms of non-HIV associated lipodystrophy. Safety issues have been discussed. Recent patent submissions have also been reviewed. PMID- 26556496 TI - Shotgun Mitogenomics Provides a Reference Phylogenetic Framework and Timescale for Living Xenarthrans. AB - Xenarthra (armadillos, sloths, and anteaters) constitutes one of the four major clades of placental mammals. Despite their phylogenetic distinctiveness in mammals, a reference phylogeny is still lacking for the 31 described species. Here we used Illumina shotgun sequencing to assemble 33 new complete mitochondrial genomes, establishing Xenarthra as the first major placental clade to be fully sequenced at the species level for mitogenomes. The resulting data set allowed the reconstruction of a robust phylogenetic framework and timescale that are consistent with previous studies conducted at the genus level using nuclear genes. Incorporating the full species diversity of extant xenarthrans points to a number of inconsistencies in xenarthran systematics and species definition. We propose to split armadillos into two distinct families Dasypodidae (dasypodines) and Chlamyphoridae (euphractines, chlamyphorines, and tolypeutines) to better reflect their ancient divergence, estimated around 42 Ma. Species delimitation within long-nosed armadillos (genus Dasypus) appeared more complex than anticipated, with the discovery of a divergent lineage in French Guiana. Diversification analyses showed Xenarthra to be an ancient clade with a constant diversification rate through time with a species turnover driven by high but constant extinction. We also detected a significant negative correlation between speciation rate and past temperature fluctuations with an increase in speciation rate corresponding to the general cooling observed during the last 15 My. Biogeographic reconstructions identified the tropical rainforest biome of Amazonia and the Guiana Shield as the cradle of xenarthran evolutionary history with subsequent dispersions into more open and dry habitats. PMID- 26556499 TI - Longitudinal Change in Thigh Muscle Strength Prior to and Concurrent With Minimum Clinically Important Worsening or Improvement in Knee Function: Data From the Osteoarthritis Initiative. AB - OBJECTIVE: To investigate whether a clinically relevant change in knee function in patients with or at risk for osteoarthritis (OA) of the knee is associated with concurrent or prior change in thigh muscle strength. METHODS: Participants in the Osteoarthritis Initiative (n = 2,675 [1,485 women and 1,190 men]) with available measurements of isometric muscle strength at baseline, 2-year follow up, and 4-year follow-up were grouped into those with greater than minimum clinically important worsening (score of >=6 [of a possible 68] on the Western Ontario and McMaster Universities Osteoarthritis Index function subscale) between 2-year follow-up and 4-year follow-up, those with greater than minimum clinically important improvement, and those without relevant change. Changes in isometric muscle strength concurrent with function change (between 2-year follow-up and 4 year follow-up) and preceding function change (between baseline and 2-year follow up), with 95% confidence intervals (95% CIs), were determined, and differences between groups were assessed by analysis of covariance. RESULTS: Concurrent loss in extensor muscle strength in participants with worsening knee function during the 2-year follow-up-4-year follow-up period differed significantly from that in participants without change in knee function (-4.6% [95% CI -6.8, -2.4] and -2.2% [95% CI -3.0, -1.4], respectively; P = 0.03), as did the concurrent increase in strength among those with functional improvement (2.2% [95% CI -0.3, 4.7]; P < 0.0001). This increase in strength among subjects with improved function remained significantly different from the change in subjects with no change in function after adjustment for covariates, but was preceded by a greater loss in strength ( 7.7% [95% CI -10.3, -5.0], P = 0.02) during the baseline-year 2 period compared to those without change in function during the year 2-year 4 period (-4.3% [95% CI -5.2, -3.4]). The decrease in strength during the baseline-year 2 period in those with worsening knee function during the year 2-year 4 period (-4.5% [95% CI -6.9, -2.2]) did not differ significantly from that in patients without a change in function (P = 0.87). No differences in changes in flexor muscle strength were observed between groups. CONCLUSION: These findings suggest that there is a positive concurrent longitudinal association between change in extensor muscle strength and worsening/improvement in knee function in patients with knee OA. However, a corresponding change in thigh muscle strength preceding the change in function was not observed. PMID- 26556500 TI - Considerations for initial therapy in the treatment of acute heart failure. AB - The diagnosis of patients presenting to the emergency department with acute heart failure (AHF) is challenging due to the similarity of AHF symptoms to other conditions such as chronic obstructive pulmonary disease and pneumonia. Additionally, because AHF is most common in an older population, the presentation of coexistent pathologies further increases the challenge of making an accurate diagnosis and selecting the most appropriate treatment. Delays in the diagnosis and treatment of AHF can result in worse outcomes and higher healthcare costs. Rapid initiation of treatment is thus necessary for optimal disease management. Early treatment decisions for patients with AHF can be guided by risk stratification models based on initial clinical data, including blood pressure, levels of troponin, blood urea nitrogen, serum creatinine, B-type natriuretic peptide, and ultrasound. In this review, we discuss methods for differentiating high-risk and low-risk patients and provide guidance on how treatment decisions can be informed by risk-level assessment. Through the use of these approaches, emergency physicians can play an important role in improving patient management, preventing unnecessary hospitalizations, and lowering healthcare costs. This review differs from others published recently on the topic of treating AHF by providing a detailed examination of the clinical utility of diagnostic tools for the differentiation of dyspneic patients such as bedside ultrasound, hemodynamic changes, and interrogation of implantable cardiac devices. In addition, our clinical guidance on considerations for initial pharmacologic therapy in the undifferentiated patient is provided. It is crucial for emergency physicians to achieve an early diagnosis of AHF and initiate therapy in order to reduce morbidity, mortality, and healthcare costs. PMID- 26556501 TI - Effect of ATM and HDAC Inhibition on Etoposide-Induced DNA Damage in Porcine Early Preimplantation Embryos. AB - Oocyte maturation and embryonic development are sensitive to DNA damage. Compared with somatic cells or oocytes, little is known about the response to DNA damage in early preimplantation embryos. In this study, we examined DNA damage checkpoints and DNA repair mechanisms in parthenogenetic preimplantation porcine embryos. We found that most of the etoposide-treated embryos showed delay in cleavage and ceased development before the blastocyst stage. In DNA-damaged embryos, the earliest positive TUNEL signals were detected on Day 5 of in vitro culture. Caffeine, which is an ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related protein) kinase inhibitor, and KU55933, which is an ATM kinase inhibitor, were equally effective in rescuing the etoposide-induced cell-cycle blocks. This indicates that ATM plays a central role in the regulation of the checkpoint mechanisms. Treating the embryos with histone deacetylase inhibitors (HDACi) increased embryonic development and reduced etoposide-induced double-strand breaks (DSBs). The mRNA expression of genes involved in non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways for DSB repair was reduced upon HDACi treatment in 5-day-old embryos. Furthermore, HDACi treatment increased the expression levels of pluripotency related genes (OCT4, SOX2 and NANOG) and decreased the expression levels of apoptosis-related genes (CASP3 and BAX). These results indicate that early embryonic cleavage and development are disturbed by etoposide-induced DNA damage. ATMi (caffeine or KU55933) treatment bypasses the checkpoint while HDACi treatment improves the efficiency of DSB repair to increase the cleavage and blastocyst rate in porcine early preimplantation embryos. PMID- 26556502 TI - Public Data Archiving in Ecology and Evolution: How Well Are We Doing? AB - Policies that mandate public data archiving (PDA) successfully increase accessibility to data underlying scientific publications. However, is the data quality sufficient to allow reuse and reanalysis? We surveyed 100 datasets associated with nonmolecular studies in journals that commonly publish ecological and evolutionary research and have a strong PDA policy. Out of these datasets, 56% were incomplete, and 64% were archived in a way that partially or entirely prevented reuse. We suggest that cultural shifts facilitating clearer benefits to authors are necessary to achieve high-quality PDA and highlight key guidelines to help authors increase their data's reuse potential and compliance with journal data policies. PMID- 26556503 TI - Antarctic glacio-eustatic contributions to late Miocene Mediterranean desiccation and reflooding. AB - The Messinian Salinity Crisis (MSC) was a marked late Neogene oceanographic event during which the Mediterranean Sea evaporated. Its causes remain unresolved, with tectonic restrictions to the Atlantic Ocean or glacio-eustatic restriction of flow during sea-level lowstands, or a mixture of the two mechanisms, being proposed. Here we present the first direct geological evidence of Antarctic ice sheet (AIS) expansion at the MSC onset and use a delta(18)O record to model relative sea-level changes. Antarctic sedimentary successions indicate AIS expansion at 6 Ma coincident with major MSC desiccation; relative sea-level modelling indicates a prolonged ~50 m lowstand at the Strait of Gibraltar, which resulted from AIS expansion and local evaporation of sea water in concert with evaporite precipitation that caused lithospheric deformation. Our results reconcile MSC events and demonstrate that desiccation and refilling were timed by the interplay between glacio-eustatic sea-level variations, glacial isostatic adjustment and mantle deformation in response to changing water and evaporite loads. PMID- 26556504 TI - Exchanging the liquidity hypothesis: Delay discounting of money and self-relevant non-money rewards. AB - Evidence that primary rewards (e.g., food and drugs of abuse) are discounted more than money is frequently attributed to money's high degree of liquidity, or exchangeability for many commodities. The present study provides some evidence against this liquidity hypothesis by contrasting delay discounting of monetary rewards (liquid) and non-monetary commodities (non-liquid) that are self-relevant and utility-matched. Ninety-seven (97) undergraduate students initially completed a conventional binary-choice delay discounting of money task. Participants returned one week later and completed a self-relevant commodity delay discounting task. Both conventional hypothesis testing and more-conservative tests of statistical equivalence revealed correspondence in rate of delay discounting of money and self-relevant commodities, and in one magnitude condition, less discounting for the latter. The present results indicate that liquidity of money cannot fully account for the lower rate of delay discounting compared to non money rewards. PMID- 26556505 TI - Assessing Measurement Invariance for Spanish Sentence Repetition and Morphology Elicitation Tasks. AB - PURPOSE: The purpose of this study was to evaluate evidence supporting the construct validity of two grammatical tasks (sentence repetition, morphology elicitation) included in the Spanish Screener for Language Impairment in Children (Restrepo, Gorin, & Gray, 2013). We evaluated if the tasks measured the targeted grammatical skills in the same way across predominantly Spanish-speaking children with typical language development and those with primary language impairment. METHOD: A multiple-group, confirmatory factor analytic approach was applied to examine factorial invariance in a sample of 307 predominantly Spanish-speaking children (177 with typical language development; 130 with primary language impairment). The 2 newly developed grammatical tasks were modeled as measures in a unidimensional confirmatory factor analytic model along with 3 well-established grammatical measures from the Clinical Evaluation of Language Fundamentals-Fourth Edition, Spanish (Wiig, Semel, & Secord, 2006). RESULTS: Results suggest that both new tasks measured the construct of grammatical skills for both language ability groups in an equivalent manner. CONCLUSIONS: There was no evidence of bias related to children's language status for the Spanish Screener for Language Impairment in Children Sentence Repetition or Morphology Elicitation tasks. Results provide support for the validity of the new tasks as measures of grammatical skills. PMID- 26556506 TI - Periodicity Dependence of the Built-in Electric Field in (Ba0.7Ca0.3)TiO3/Ba(Zr0.2Ti0.8)O3 Ferroelectric Superlattices. AB - Symmetric ferroelectric superlattices consisting of (Ba0.7Ca0.3)TiO3 (BCT) and Ba(Zr0.2Ti0.8)O3 (BZT) layers were successfully grown on La0.7Sr0.3MnO3 electroded (001)-oriented SrTiO3 substrates by laser molecular beam epitaxy. With the monitor of reflective high-energy electron diffraction, the growth mode and rate were precisely controlled to realize the desired superlattice periodicity as confirmed by both X-ray diffraction and transmission electron microscopy results. The microscopic piezoelectric response and macroscopic ferroelectric properties were investigated as a function of periodicity of the BCTm/BZTm (m = 3, 5, 10, and 15 unit cells) superlattices. The existence of a built-in electric field was confirmed in all the superlattices and its strength was highly dependent on the periodicity. The excellent tunability of built-in electric field opens a path for designing microelectronic devices with various functionalities based on BCTm/BZTm superlattices. PMID- 26556507 TI - Baseline Correction of Diffuse Reflection Near-Infrared Spectra Using Searching Region Standard Normal Variate (SRSNV). AB - An alternative baseline correction method for diffuse reflection near-infrared (NIR) spectra, searching region standard normal variate (SRSNV), was proposed. Standard normal variate (SNV) is an effective pretreatment method for baseline correction of diffuse reflection NIR spectra of powder and granular samples; however, its baseline correction performance depends on the NIR region used for SNV calculation. To search for an optimal NIR region for baseline correction using SNV, SRSNV employs moving window partial least squares regression (MWPLSR), and an optimal NIR region is identified based on the root mean square error (RMSE) of cross-validation of the partial least squares regression (PLSR) models with the first latent variable (LV). The performance of SRSNV was evaluated using diffuse reflection NIR spectra of mixture samples consisting of wheat flour and granular glucose (0-100% glucose at 5% intervals). From the obtained NIR spectra of the mixture in the 10 000-4000 cm(-1) region at 4 cm intervals (1501 spectral channels), a series of spectral windows consisting of 80 spectral channels was constructed, and then SNV spectra were calculated for each spectral window. Using these SNV spectra, a series of PLSR models with the first LV for glucose concentration was built. A plot of RMSE versus the spectral window position obtained using the PLSR models revealed that the 8680-8364 cm(-1) region was optimal for baseline correction using SNV. In the SNV spectra calculated using the 8680-8364 cm(-1) region (SRSNV spectra), a remarkable relative intensity change between a band due to wheat flour at 8500 cm(-1) and that due to glucose at 8364 cm(-1) was observed owing to successful baseline correction using SNV. A PLSR model with the first LV based on the SRSNV spectra yielded a determination coefficient (R2) of 0.999 and an RMSE of 0.70%, while a PLSR model with three LVs based on SNV spectra calculated in the full spectral region gave an R2 of 0.995 and an RMSE of 2.29%. Additional evaluation of SRSNV was carried out using diffuse reflection NIR spectra of marzipan and corn samples, and PLSR models based on SRSNV spectra showed good prediction results. These evaluation results indicate that SRSNV is effective in baseline correction of diffuse reflection NIR spectra and provides regression models with good prediction accuracy. PMID- 26556508 TI - Team Editorial. PMID- 26556509 TI - Dean's Update. PMID- 26556510 TI - Membership Update. PMID- 26556511 TI - FGDP(UK) Divisional Update. PMID- 26556512 TI - Interface Between Dementia and Oral Health Event. PMID- 26556513 TI - Patients' Priorities and Attitudes Towards Their Temporo-Mandibular Disorders. AB - The diagnosis and appropriate management of temporo-mandibular disorders (TMDs) remains controversial. Current scientific evidence highlights the importance of psychosocial factors in sufferers and the reducing emphasis on occlusal or dental/prosthetic factors. This paper describes the findings of a survey of 211 patients reporting pain from their temporo-mandibular joint area and associated structures. This article offers busy primary dental care practitioners a cost effective questionnaire for obtaining relevant information from patients about the history of their condition and highlights what patients hope to achieve through the management of their disorder. It also emphasises the importance of communicating effectively with patients and offers practical tips for the management of TMDs in primary care. PMID- 26556514 TI - Credibility and Confidence in Your Dental Laboratory Work-How Quality Assurance Systems Can Be Used in the Manufacturing of Individual Custom-Made Dental Devices. AB - Manufacturing of custom-made dental devices such as removable dentures, fixed prosthodontics and orthodontics are subject to the requirements of the Medical Devices Directive (MDD). Many dental laboratories often enhance these requirements by implementing quality assurance procedures that then provide enhanced consistency. This paper provided a personal view of some of the systems currently being used in dental laboratories to provide a quality assured product and associated issues. PMID- 26556515 TI - Risk Assessment for Tooth Wear. AB - Tooth wear has an increasing prevalence in the UK population. The aetiology is commonly multifactorial, and the aetiopathology is through a combination of erosion, attrition, abrasion and abfraction. Erosion is associated with intrinsic or extrinsic acids, and therefore subjects with reflux disease and eating disorders are at increased risk. Fruit juice, fruits and carbonated drink consumption, frequency of consumption and specific habits are also risk factors. Attrition is more prevalent in bruxists. Other habits need to be considered when defining the risk of tooth wear. Abrasion is usually associated with toothbrushing and toothpastes, especially in an already acidic environment. Patients with extensive lesions that affect dentin may be at higher risk, as well as those presenting with unstained lesions. Monitoring of the progress of tooth wear is recommended to identify those with active tooth wear. Indices for tooth wear are a helpful aid. PMID- 26556516 TI - Bisphosphonate and Implant Dentistry - Is it Safe? AB - Bisphosphonates are a group of drugs that are commonly used to alter bone metabolism in order to prevent bone loss in diseases such as osteoporosis and bone cancers. Unfortunately, the use of bisphosphonates has been associated with bisphosphonate-related osteonecrosis of the jaws. The debate as to whether it is wise to consider implant therapy in patients being treated with bisphosphonate therapy remains a grey area. This review will present the latest evidence and guidelines available on bisphosphonates and their possible effects on implant dentistry. The risk factors, co-morbidities, clinical presentation and findings from various imaging modalities for bisphosphonate-related osteonecrosis of the jaws are highlighted. The management of patients being treated with bisphosphonates, in whom dental implants might be considered or have already been placed, will also be discussed. Finally, the areas requiring future research are considered. PMID- 26556517 TI - Reducing Harm in Healthcare Systems. AB - An understanding of the importance of causation of medical errors is important for determining strategies to reduce the harm that they can cause to patients. This paper discusses how dentistry can learn from medicine as well as other industries when developing approaches designed to deal with the causes of errors, rather than their outcomes. PMID- 26556518 TI - Risk Assessment Protocol in an Nhs Practice--A Team Approach. PMID- 26556519 TI - Infographic: An Introduction to the Faculty. PMID- 26556520 TI - The Prevention and Management of Dry Socket: Do Antibiotics Have a Role to Play? PMID- 26556522 TI - Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets. AB - Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources. PMID- 26556523 TI - Withdrawal from Chronic Alcohol Induces a Unique CCL2 mRNA Increase in Adolescent But Not Adult Brain--Relationship to Blood Alcohol Levels and Seizures. AB - BACKGROUND: The role of neuroimmune activation in withdrawal from chronic alcohol (ethanol) has been established in both adolescent and adult models, but direct comparisons across age are sparse. Studies need to elucidate age-dependent neuroimmune effects of alcohol and to focus research attention on age-dependent mechanisms and outcomes. METHODS: Adult and adolescent rats from 2 commonly used strains, Wistar and Sprague Dawley (SD), were maintained on continuous 7%, 5.35%, 4.5% alcohol diet (CAD) or cycled 7% w/v alcohol diet for 15 days. Cortical tissue was collected at 0, 8, 16, and 24 hours postwithdrawal followed by measurement of chemokine (C-C motif) ligand 2 (CCL2), tumor necrosis factor alpha, and interleukin 1 beta mRNA with quantitative real-time polymerase chain reaction. RESULTS: Both age groups and strains showed a strong cytokine mRNA response at 7% CAD. Further, a greater increase in CCL2 mRNA was observed in the cortex of adolescents at 7% CAD, which correlated with higher blood alcohol levels (BALs). Adolescents exposed to 5.35% CAD exhibited similar blood levels and cytokine responses as adults exposed to 7% CAD. Substantial variability in CCL2 mRNA responses was found only in adolescent rats exposed to 7% CAD. In this group, data could be segregated into high-responding and low-responding groups. Moreover, the data from the high-responding group were associated with seizures. CONCLUSIONS: Relative to other cytokine mRNAs, CCL2 exhibits a unique response profile during withdrawal from CAD. This profile is shown in adolescents, where CCL2 is uniquely influenced by the effects of seizures. Additionally, this profile is shown by the fact that only CCL2 expression correlated with BAL that transcended age groups. These data emphasize the importance of BALs and treatment regimen on developmental neuroimmune responses and suggest that select components of the neuroimmune system are more responsive to CAD withdrawal and that neurobiological mechanisms differentiating these responses should be further explored. PMID- 26556524 TI - Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction. AB - To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 850.01). Among the 43 A. actinomycetemcomitans-positive samples, the serotype was identified in 21 samples. Fifteen were positive for A. actinomycetemcomitans serotype a, 1 for serotype b, 1 for serotype c, and 4 for serotype f, while serotypes d and e were not detected. CONCLUSION: A. actinomycetemcomitans serotype a is the most commonly found serotype among Turkish dental students without periodontitis. PMID- 26556548 TI - Middle mesial canals in mandibular first molars: A micro-CT study in different populations. AB - OBJECTIVE: To describe the morphological aspects of middle mesial canals (MMC) in mandibular first molars using micro-CT. DESIGN: Mandibular first molars collected from the Brazilian (n=136) and Turkish (n=122) populations were scanned (voxel size: 9.9MUm) and mesial roots with MMC (n=48) evaluated regarding several morphological aspects. The incidence of MMC in each population was statistically compared using Chi-square test (alpha=0.05). RESULTS: Overall, the incidence of MMC was 18.6% (48 out of 258 molars) and was significantly higher in the Brazilian (n=30; 22.1%) than in the Turkish (n=18; 14.8%) population (p<0.05). In both populations, confluent configuration of the MMC was the most frequent anatomy. Most of the specimens with MMC had 3 independent orifices (n=26; 54.2%) and 3 apical foramina (n=21; 43.8%). The mean minor diameter of the MMC orifice (0.16mm) was 3 times less than the other orifices (~0.50mm). In mesial roots with independent configuration (n=3; 6.3%), the mean volumes (mm(3)) of the MMC, mesiobuccal (MBC) and mesiolingual (MLC) canals were 0.20+/-0.10, 0.75+/-0.28, and 0.88+/-0.19, respectively. In the specimens with canal confluence (n=26; 54.2%), MMC merged to the MBC (n=8; 16.7%), MLC (n=4; 8.3%), or to both MBC and MLC (n=14; 29.2%). Double mesial canal was observed in only 1 specimen. MMC with an independent foramen was observed mostly in Brazilian specimens. CONCLUSIONS: Incidence of MMC was higher in the Brazilian molars. Confluent configuration was the most prevalent anatomic variation, while independent and fin configurations, as well as, double MMC, were found only in a few specimens. PMID- 26556549 TI - Predictors of adherence to safe handling practices for antineoplastic drugs: A survey of hospital nurses. AB - Despite growing awareness of the hazards of exposure to antineoplastic drugs (ADs), surveys continue to find incomplete adherence to recommended safe handling guidelines. A 2011 survey of healthcare workers presents an opportunity to examine factors associated with adherence among 1094 hospital nurses who administered ADs. Data for these hypothesis-generating analyses were taken from an anonymous, web-based survey of healthcare workers. Regression modeling was used to examine associations between a number of predictors (engineering controls, work practices, nurse perceptions, and nurse and hospital characteristics) and three outcomes reported by nurses: use of personal protective equipment (PPE); activities performed with gloves previously worn to administer ADs; and spills of ADs. Adherence to safe handling guidelines was not universal, and AD spills were reported by 9.5% of nurses during the week prior to the survey. Familiarity with safe handling guidelines and training in safe handling were associated with more reported PPE use. Nurse-perceived availability of PPE was associated with more reported PPE use and lower odds of reported spills. Use of closed system drug-transfer devices and luer-lock fittings also decreased the odds of self-reported AD spills, while more frequent AD administration increased the risk. AD administration frequency was also associated with performing more activities with gloves previously worn to administer ADs, and nurse perception of having adequate time for taking safety precautions with fewer such activities. The results suggest that training and familiarity with guidelines for safe handling of ADs, adequate time to adhere to guidelines, and availability of PPE and certain engineering controls are key to ensuring adherence to safe handling practices. Further assessment of training components and engineering controls would be useful for tailoring interventions targeting these areas. PMID- 26556550 TI - CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia. AB - Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8(+) T-cell-mediated ITP using a murine model. CD61 knockout (KO) mice were immunized with CD61(+) platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD61(+) platelet immunization. This resulted in efficient Bdep in vivo, accompanied by significant increases in splenic and lymph node CD4(+) and CD8(+) T cells and proportional increases of FOXP3(+) in CD4(+)and CD8(+) T cells. Moreover, Bdep therapy resulted in significantly decreased splenic CD8(+) T-cell proliferation in vitro that could be rescued by interleukin-2. This correlated with normalization of in vivo platelet counts in the transferred SCID mice suggesting that anti-CD20 therapy significantly reduces the ability of CD8(+) T cells to activate and mediate ITP. PMID- 26556551 TI - Possible mechanism by which renal sympathetic denervation improves left ventricular remodelling after myocardial infarction. AB - NEW FINDINGS: What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-beta1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-beta1 (TGF-beta1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-beta1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-beta1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction. PMID- 26556553 TI - Medical-legal partnerships: the role of mental health providers and legal authorities in the development of a coordinated approach to supporting mental health clients' legal needs in regional and rural settings. AB - INTRODUCTION: Medical-legal partnerships (MLP) are a model in which medical and legal practitioners are co-located and work together to support the health and wellbeing of individuals by identifying and resolving legal issues that impact patients' health and wellbeing. The aim of this article is to analyse the benefits of this model, which has proliferated in the USA, and its applicability in the context of rural and remote Australia. METHODS: This review was undertaken with three research questions in mind: What is an MLP? Is service provision for individuals with mental health concerns being adequately addressed by current service models particularly in the rural context? Are MLPs a service delivery channel that would benefit individuals experiencing mental health issues? RESULTS: The combined searches from all EBSCO Host databases resulted in 462 citations. This search aggregated academic journals, newspapers, book reviews, magazines and trade publications. After several reviews 38 papers were selected for the final review based on their relevance to this review question: How do MLPs support mental health providers and legal service providers in the development of a coordinated approach to supporting mental health clients' legal needs in regional and rural Australia? CONCLUSIONS: There is considerable merit in pursuing the development of MLPs in rural and remote Australia particularly as individuals living in rural and remote areas have far fewer opportunities to access support services than those people living in regional and metropolitan locations. MLPS are important channels of service delivery to assist in early invention of legal problems that can exacerbate mental health problems. PMID- 26556552 TI - Cardiac ion channels. AB - Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID- 26556554 TI - Study of secondary neutron interactions with 232Th, 129I, and 127I nuclei with the uranium assembly "QUINTA" at 2, 4, and 8 GeV deuteron beams of the JINR Nuclotron accelerator. AB - The natural uranium assembly, "QUINTA", was irradiated with 2, 4, and 8GeV deuterons. The (232)Th, (127)I, and (129)I samples have been exposed to secondary neutrons produced in the assembly at a 20-cm radial distance from the deuteron beam axis. The spectra of gamma rays emitted by the activated (232)Th, (127)I, and (129)I samples have been analyzed and several tens of product nuclei have been identified. For each of those products, neutron-induced reaction rates have been determined. The transmutation power for the (129)I samples is estimated. Experimental results were compared to those calculated with well-known stochastic and deterministic codes. PMID- 26556555 TI - Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis. AB - Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity. PMID- 26556556 TI - Investigation of Suspected Pulmonary Embolism at Hutt Valley Hospital with CT Pulmonary Angiography: Current Practice and Opportunities for Improvement. AB - Aims. To study the use of CT pulmonary angiography (CTPA) at Hutt Hospital and investigate the use of pretest probability scoring in the assessment of patients with suspected pulmonary embolism (PE). Methods. We studied patients with suspected PE that underwent CTPA between January and May 2012 and collected data on demographics, use of pretest probability scoring, and use of D Dimer and compared our practice with the British Thoracic Society (BTS) guideline. Results. 105 patients underwent CTPA and 15% of patients had PE. 13% of patients had a Wells score prior to their scan. Wells score calculated by researchers revealed 54%, 36%, and 8% patients had low, medium, and high risk pretest probabilities and 8%, 20%, and 50% of these patients had positive scans. D Dimer was performed in 58% of patients and no patients with a negative D Dimer had a PE. Conclusion. The CTPA positive rate was similar to other contemporary studies but lower than previous New Zealand studies and some international guidelines. Risk stratification of suspected PE using Wells score and D Dimer was underutilised. A number of scans could have been safely avoided by using accepted guidelines reducing resources use and improving patient safety. PMID- 26556557 TI - A Critical Analysis of Claims and Their Authenticity in Indian Drug Promotional Advertisements. AB - Introduction. Drug promotional advertisements (DPAs) form a major marketing technique of pharmaceutical companies for promoting their products and disseminating ambiguous drug information which can affect prescribing pattern of physicians. Drug information includes product characteristics, various marketing claims with references in support to increase its credibility and authenticity. Material and Methods. An observational study was carried out on fifty printed drug advertisement brochures which were collected from different OPDs of Guru Nanak Dev Hospital attached to Government Medical College, Amritsar, India. These advertisements were analyzed and claims were categorized into true, false, exaggerated, vague, and controversial on criteria as reported by Rohraa et al. (2006). References of DPAs in support of the claims were critically analyzed for their retrievability from web and validity pertaining to claims. Results. Out of 209 claims from 50 advertisements, only 46% were found to be true, 21% false, 16% vague, 7% exaggerated, and 10% controversial in nature. Out of 160 references given in support of claims, 49 (30%) of references were irretrievable. Out of 111 (70%) retrievable references, 92 (83%) references were found valid. Conclusion. Drug information provided in the DPAs was biased, incomplete, unauthentic, and unreliable with references exhibiting questionable credibility. PMID- 26556558 TI - The Knowledge, Attitude, and Perception towards Epilepsy amongst Medical Students in Uyo, Southern Nigeria. AB - Background and Aim. Epilepsy remains a stigmatized disease especially in Sub Saharan Africa. Lack of information and illiteracy has been blamed as the cause of the stigmatization. This stigmatization stems from the fact that the traditional African belief views epilepsy as a spiritual disease. We studied the knowledge, attitude, and perception towards epilepsy amongst medical students comparing the knowledge of the clinical students with that of the basic medical (preclinical) students. Methodology. The participants were medical students in University of Uyo. We administered questionnaires which explored the knowledge of etiology (perceived and medically proven). We studied the beliefs in infectivity of epilepsy, treatment together with their attitudes, and perception to persons with epilepsy. Results. Most of the participants do not have a good knowledge of epilepsy. The knowledge, however, was much better amongst the clinical students. There is some difference in the attitudes of the clinical students compared with the basic students. Conclusion. There is a knowledge gap in epilepsy even amongst medical students. Participants still harbor the traditional African beliefs that epilepsy is a spiritual disease. Mercifully, the knowledge is better amongst the clinical students. This is not surprising since the clinical students have had clinical exposure to epilepsy. PMID- 26556559 TI - Mathematical Modelling and Tuberculosis: Advances in Diagnostics and Novel Therapies. AB - As novel diagnostics, therapies, and algorithms are developed to improve case finding, diagnosis, and clinical management of patients with TB, policymakers must make difficult decisions and choose among multiple new technologies while operating under heavy resource constrained settings. Mathematical modelling can provide helpful insight by describing the types of interventions likely to maximize impact on the population level and highlighting those gaps in our current knowledge that are most important for making such assessments. This review discusses the major contributions of TB transmission models in general, namely, the ability to improve our understanding of the epidemiology of TB. We focus particularly on those elements that are important to appropriately understand the role of TB diagnosis and treatment (i.e., what elements of better diagnosis or treatment are likely to have greatest population-level impact) and yet remain poorly understood at present. It is essential for modellers, decision makers, and epidemiologists alike to recognize these outstanding gaps in knowledge and understand their potential influence on model projections that may guide critical policy choices (e.g., investment and scale-up decisions). PMID- 26556560 TI - Use of Virtual Reality Tools for Vestibular Disorders Rehabilitation: A Comprehensive Analysis. AB - Classical peripheral vestibular disorders rehabilitation is a long and costly process. While virtual reality settings have been repeatedly suggested to represent possible tools to help the rehabilitation process, no systematic study had been conducted so far. We systematically reviewed the current literature to analyze the published protocols documenting the use of virtual reality settings for peripheral vestibular disorders rehabilitation. There is an important diversity of settings and protocols involving virtual reality settings for the treatment of this pathology. Evaluation of the symptoms is often not standardized. However, our results unveil a clear effect of virtual reality settings-based rehabilitation of the patients' symptoms, assessed by objectives tools such as the DHI (mean decrease of 27 points), changing symptoms handicap perception from moderate to mild impact on life. Furthermore, we detected a relationship between the duration of the exposure to virtual reality environments and the magnitude of the therapeutic effects, suggesting that virtual reality treatments should last at least 150 minutes of cumulated exposure to ensure positive outcomes. Virtual reality offers a pleasant and safe environment for the patient. Future studies should standardize evaluation tools, document putative side effects further, compare virtual reality to conventional physical therapy, and evaluate economical costs/benefits of such strategies. PMID- 26556561 TI - Transmission in near-infrared optical windows for deep brain imaging. AB - Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. PMID- 26556562 TI - Assessment of Enterotoxin Production and Cross-Contamination of Staphylococcus aureus between Food Processing Materials and Ready-To-Eat Cooked Fish Paste. AB - This study evaluated Staphylococcus aureus growth and subsequent staphylococcal enterotoxin A production in tryptone soy broth and on ready-to-eat cooked fish paste at 12 to 37 degrees C, as well as cross-contamination between stainless steel, polyethylene, and latex glove at room temperature. A model was developed using Barany and Roberts's growth model, which satisfactorily described the suitable growth of S. aureus with R(2)-adj from 0.94 to 0.99. Except at 12 degrees C, S. aureus cells in TSB presented a lag time lower (14.64 to 1.65 h), grew faster (0.08 to 0.31 log CFU/h) and produced SEA at lower cell density levels (5.65 to 6.44 log CFU/mL) compare to those inoculated on cooked fish paste with data of 16.920 to 1.985 h, 0.02 to 0.23 log CFU/h, and 6.19 to 7.11 log CFU/g, respectively. Staphylococcal enterotoxin type A (SEA) visual immunoassay test showed that primary SEA detection varied considerably among different storage temperature degrees and media. For example, it occurred only during exponential phase at 30 and 37 degrees C in TSB, but in cooked fish paste it took place at late exponential phase of S. aureus growth at 20 and 25 degrees C. The SEA detection test was negative on presence of S. aureus on cooked fish paste stored at 12 and 15 degrees C, although cell density reached level of 6.12 log CFU/g at 15 degrees C. Cross-contamination expressed as transfer rate of S. aureus from polyethylene surface to cooked fish paste surface was slower than that observed with steel surface to cooked fish paste under same conditions. These results provide helpful information for controlling S. aureus growth, SEA production and cross-contamination during processing of cooked fish paste. PMID- 26556563 TI - Genetic association of left ventricular mass assessed by M-mode and two dimensional echocardiography. AB - BACKGROUND: Left ventricular mass offers prognostic information for assessing cardiovascular disease risk. M-mode and two-dimensional (2D) echocardiographically-derived left ventricular mass values have shown high accuracy and reproducibility; however, no studies to date have compared left ventricular mass genetic association findings on the basis of both the methods. The aim of this study was to compare associations of single-nucleotide polymorphisms (SNPs) from genome-wide association study analyses of left ventricular mass using both methods in the same cohort. METHODS AND RESULTS: Left ventricular mass was determined using 2D and M-mode echocardiography in 711 patients (390 women); SNP genotype data were obtained using the Genome-wide Human SNP Array 6.0. Genome-wide association study analyses were performed to obtain panels of SNPs associated with left ventricular mass and left ventricular mass index. The unindexed left ventricular mass showed excellent agreement [M-mode: 170 +/- 47 vs. 2D: 178 +/- 56 g; intraclass correlation coefficient 0.929 (95% confidence interval 0.932, 0.909)]. The presence of left ventricular hypertrophy based on M-mode and 2D-derived left ventricular mass index values showed moderate agreement (kappa = 0.49). Eleven SNPs showed suggestive association with at least two of the four left ventricular mass traits, with one SNP in CDH13 common to all four derived traits. CONCLUSION: M-mode and 2D echocardiography left ventricular mass measurements in the same cohort identified suggestive genetic associations, both shared and unshared, suggesting common left ventricular mass biology underlying the two measures of left ventricular mass. The combined use of M-mode and 2D echo is a novel approach that may increase the yield of genetic association with left ventricular mass. PMID- 26556565 TI - Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system. AB - In past decades, growing evidence from basic and clinical researches reveal that small guanosine triphosphate binding protein ras homolog gene family, member A (RhoA) and its main effector Rho-associated kinase (ROCK) play central and complex roles in cardiovascular systems, and increasing RhoA and ROCK activity is associated with a broad range of cardiovascular diseases such as congestive heart failure, atherosclerosis, and hypertension. Favorable outcomes have been observed with ROCK inhibitors treatment. In this review, we briefly summarize the pathophysiological roles of RhoA/ROCK signaling pathway on cardiovascular system, displaying the potential benefits in the cardiovascular system with controlling RhoA/ROCK signaling pathway. PMID- 26556564 TI - Analysis and validation of traits associated with a single nucleotide polymorphism Gly364Ser in catestatin using humanized chromogranin A mouse models. AB - OBJECTIVE: The human prohormone chromogranin A (CHGA), an index member of the granin family is processed to generate catestatin, a peptide that is hypotensive in action and modulates catecholamine release within the sympathoadrenal system. Hypertensive patients with excess sympathetic activity have diminished catestatin. Often the study of physiological consequences of human genetic variation is confounded by elements such as other variations in obligatory linkage disequilibrium with the variant being studied. Also the phenotype of the variant may be influenced by genetic background that varies amongst individuals. This study addresses the effects of a human catestatin polymorphism (rs9658667) using humanized CHGA mouse models. METHODS: We created pertinent humanized mouse models wherein the mouse Chga gene locus was replaced by the human ortholog wild type and the variant versions. This allowed for probing of the effects of catestatin variation in vivo with controls for other variations and global genetic background. RESULTS: Both the wild-type and variant human catestatin expressing mouse models were normotensive. The variant catestatin mouse model recapitulated physiological influence of the polymorphism on autonomic traits. These mice had diminished catecholamine, attenuated stress response and increased baroreceptor slopes that would suggest reduced risk of developing hypertension. Elevated plasma glucose, a trait observed in humans was not observed in mice expressing the variant catestatin. CONCLUSION: This functional genomics approach of creating humanized mouse models to study rs9658667 polymorphism recapitulated and validated many of the human trait associations. This approach can also be applied in the study of other human gene polymorphisms. PMID- 26556566 TI - Hypertension and lifetime risk of stroke. AB - BACKGROUND: The lifetime risk (LTR) articulates the probability of disease in the residual lifetime for an index age. These estimates can be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on lifetime of impact of hypertension on stroke events in Asians in whom stroke incidence is higher than Westerners. METHODS: The Suita Study, a cohort study of cardiovascular diseases in Japan, was established in 1989. We included all participants who were stroke free at baseline. Age (in years) was used as the time scale. Age-specific incidence rates were calculated with person-year method within 10-year bands. We estimated the sex and index-age specific LTR of first-ever stroke with taking the competing risk of death into account. RESULTS: We followed 5783 men and women during 1989-2007 for 74 933 person-years. During the follow-up period, 276 (149 men and 127 women) participants had incident stroke. Of them, majority were cerebral infarction; 166 (102 men and 64 women). The LTR of stroke, accounted for competing risk of death, at 45 years of age for men without hypertension was 17.21% and it was 32.79% for hypertensive men. Among the hypertensive patients, participants with stage 2 or greater hypertension had higher LTR of stroke than the participants with stage 1 hypertension. This increased LTR of stroke for hypertensive patients were also observed among women and across all index ages for stroke. CONCLUSION: In this urban community-based population, we observed that hypertension has significant effect on the residual LTR of stroke among both men and women of middle age, specifically for ischemic stroke. PMID- 26556567 TI - Predictors of response to renal denervation for resistant arterial hypertension: a single center experience. AB - BACKGROUND: Renal denervation (RDN) has been shown to reduce blood pressure in patients with resistant arterial hypertension (RAH). We aimed to investigate predictors for response to RDN. METHODS: Patients suffering from RAH underwent RDN after exclusion of secondary causes of hypertension. Ambulatory blood pressure measurement (ABPM) for 24 h was performed at baseline, 6 and 12 months after RDN. Response was defined as a at least 5 mmHg 24 h SBP drop at 6 months. A linear regression model was used to analyze an association between baseline variables and response to RDN. RESULTS: In total, 45.6% of patients were responders to RDN. In those, there was a significant reduction in ABPM values at 6 and 12 months (12 months: 24 h SBP: -17.2 +/- 9.0 mmHg, P < 0.01; 24 h DBP: 9.0 +/- 11.6 mmHg, P < 0.01). Per 10 mmHg increase in baseline 24 h SBP, there was a 5.5 mmHg 24 h SBP reduction at 6 months. Per kg/m increase in BMI, 24 h SBP increased by 0.7 mmHg at 6 months. Per increment in antihypertensive drugs used at baseline, there was a 2.7 mmHg 24 h SBP reduction at 6 months. CONCLUSION: Out of a wide range of baseline variables, elevated systolic ABPM values, BMI and the number of antihypertensive drugs used were associated with response. One has to consider the Hawthorne effect, the regression to the mean phenomenon, the actual effect of sympathetic denervation and the interaction of therapy modification when interpreting data from RDN registries without a control arm. PMID- 26556568 TI - Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium: systematic review and meta-analyses. AB - BACKGROUND: Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. METHOD: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. RESULTS: For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125~spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. CONCLUSION: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines. PMID- 26556569 TI - [Systemic Treatment of Metastatic Renal Cell Cancer--Back to the Future?]. AB - A variety of therapeutic agents are currently available for the systemic treatment of metastatic renal cell carcinoma (mRCC). It was only when targeted treatment was developed in the past decade that a significant improvement was achieved in tumour therapy. This also led to the development of sequential treatment for mRCC.7 molecular targeted agents are available today (axitinib, bevacizumab/ IFNalpha, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus). Due to the individualisation of treatment it remains a challenge to choose the most appropriate drug in a given setting, with the choice being based on the knowledge of the relevant clinical data as well as individual patient parameters.During the recent past, efforts have been made to test different inhibitors or combinations without a major breakthrough. Instead, the development of novel specific immunotherapeutic approaches now heralds the next level of treatment in mRCC. The first significant trial results will be expected this year, and further trials for optimisation of treatment are warranted. PMID- 26556570 TI - Classifying eating-related problems among institutionalized people with dementia. AB - AIMS: Various eating-related problems are commonly observed among people with dementia, and these problems place a huge burden on the caregivers. An appropriate classification of these problems is important in order to understand their underlying mechanisms and to develop a therapeutic approach for managing them. The aim of this study was to develop a possible classification of eating related problems and to reveal the background factors affecting each of these problems across various conditions causing dementia. METHODS: The participants were 208 institutionalized patients with a diagnosis of dementia. Care staff were asked to report all kinds of eating-related problems that they observed. After the nurses' responses were analyzed, 24 items relating to eating-related problems were extracted. A factor analysis of these 24 items was conducted, followed by a logistic regression analysis to investigate the independent variables that most affected each of the eating-related factors. RESULTS: Four factors were obtained. Factor 1 was overeating, factor 2 was swallowing problems, factor 3 was decrease in appetite, and factor 4 was obsession with food. Each factor was associated with different background variables, including Mini-Mental State Examination scores, Clinical Dementia Ratings, and neuropsychiatric symptoms. CONCLUSIONS: This study suggests that eating-related problems are common across conditions causing dementia and should be separately considered in order to understand their underlying mechanisms. PMID- 26556571 TI - Antibacterial and antiplaque efficacy of a commercially available octenidine containing mouthrinse. AB - OBJECTIVES: The purpose of this clinical study was to determine the antibacterial and antiplaque efficacy of a recently introduced octenidine-containing mouthrinse (Octenidol(r)) in comparison with established antiseptic mouthrinses. MATERIALS AND METHODS: In a 4-day plaque-regrowth study employing a four-replicate cross over design, a 0.1 % octenidine mouthrinse (Octenidol(r)/OCT-MR) was compared with a 0.12 % chlorhexidine mouthrinse (Paroex(r)/CHX-MR), an essential oil mouthrinse (Listerine(r)/EO-MR), and a placebo mouthrinse/P-MR. Plaque regrowth was assessed with a modified Quigley-Hein plaque index. The antibacterial effect was assessed by taking bacterial counts from the tooth surface and oral mucosa after professional tooth cleaning and after first rinsing with the allocated mouthrinse on days 1 and 5. Sixteen volunteers suspended tooth cleaning and rinsed twice daily with the allocated mouthrinse for 4 days. RESULTS: All tested antiseptic mouthrinses were significantly more effective than the placebo mouthrinse in inhibiting plaque, but no significant differences were observed between OCT-MR and CHX-MR, OCT-MR and EO-MR, and CHX-MR and EO-MR. After 4 days, comparable bacterial count levels were found on both the tooth surface and mucosa applying OCT-MR and CHX-MR, which were significantly lower than that of EO-MR and P-MR. CONCLUSION: Octenidol(r) and Paroex(r) showed comparable antibacterial and antiplaque efficacy in the human oral cavity. CLINICAL RELEVANCE: The recently introduced octenidine-containing mouthrinse Octenidol(r) may become a suitable alternative to 0.12 % chlorhexidine-containing mouthrinses such as Paroex(r). PMID- 26556572 TI - Correlative micro-Raman/EPMA analysis of the hydraulic calcium silicate cement interface with dentin. AB - OBJECTIVES: This study aims to characterize the chemical interplay of hydraulic calcium silicate cements at dentin. MATERIALS AND METHODS: Class I cavities were prepared in non-carious human third molars and filled with Biodentine (Septodont) or ProRoot MTA (Dentsply). After 1-day, 1-week, and 1-month Dulbecco's phosphate buffered saline (DPBS) storage, the specimens were cross-sectioned perpendicular to the cement-dentin interface. The interfaces were evaluated using micro-Raman (MURaman) spectroscopy and at a higher spatial resolution using field emission gun electron probe microanalysis (Feg-SEM/EPMA). RESULTS: MURaman spectroscopy revealed the formation of a transition zone at the interface of both Biodentine (Septodont) and ProRoot MTA (Dentsply) with dentin, having an average thickness of, respectively, 7.5 +/- 4.2 and 6.2 +/- 5.4 MUm, which however was not statistically different. No difference in interfacial ultrastructure and chemistry was found using MURaman spectroscopy between 1 day, 1 week, and 1 month DPBS-stored specimens. The observation of a transition zone at the cement-dentin interfaces contrasts with the EPMA data that revealed a sharper transition from cement to dentin. Again, no difference in interfacial ultrastructure and chemistry was found for different storage periods, with the exception of one 1 month DPBS-stored specimen prepared using Biodentine (Septodont). More specifically, EPMA revealed a gap of about 10-MUm wide in the latter specimen that was filled up with newly formed calcium phosphate depositions. CONCLUSIONS: Up to 1 month, the interaction of hydraulic calcium silicate cements investigated did not reveal ultrastructural or chemical changes at unaffected dentin with the exception of a calcium phosphate gap-filling property. CLINICAL RELEVANCE: Hydraulic calcium silicate cements were found to fill gaps by calcium phosphate deposition, however, without conducting chemical changes to the adjacent dentin. PMID- 26556573 TI - The effect of fluoride varnishes on caries lesions: an in vitro investigation. AB - OBJECTIVES: The purpose of this study was to investigate the effect of five commercially available fluoride varnishes (FV) on caries lesions. MATERIALS AND METHODS: Ninety bovine enamel specimens were assigned to five varnish groups (n = 18). Early caries lesions were created in the specimens and characterized using Vickers surface microhardness number (VHN). FV was applied to each group of specimens. Immediately afterwards, 7.5 ml of artificial saliva (AS) were pipetted over each group of specimens, collected and renewed every 15 min for 6 h. AS samples were analyzed for fluoride using an ion-specific electrode. Enamel fluoride uptake (EFU) was determined using the acid etch technique. Each group was then subjected to a pH cycling regimen for 5 days after which VHN was determined again. One-way analysis of variance (ANOVA) was used for data analysis. RESULTS: FVs differed in their rehardening capability (highest mean value was for Enamel Pro = 32.3 +/- 5.8 and lowest mean value was for Vanish = 18.9 +/- 11.3). No significant difference in EFU was found among groups. Total fluoride release over 6 h was in the order of MI Varnish (303 MUg/ml) > Enamel Pro (217 MUg/ml) > Flor-Opal (153 MUg/ml) > PreviDent(84 MUg/ml) > Vanish(28 MUg/ml). CONCLUSIONS: DeltaVHN and fluoride release characteristics differ among FV products. These differences may be attributed to the different compositions and physical properties of the tested FV. CLINICAL RELEVANCE: Fundamental, comparable research on FV and how different formulations affect early caries lesion rehardening, fluoride release into saliva, and uptake by teeth is scarce. PMID- 26556574 TI - Evaluation of the mandibular volume and correlating variables in patients affected by unilateral and bilateral cleft lip and palate: a cone-beam computed tomography study. AB - OBJECTIVES: The aims of the present study were to evaluate the mandibular volume in patients affected by unilateral (UCLP) and bilateral cleft lip and palate (BCLP) and to compare the findings with a well-matched normal occlusion sample without cleft. MATERIALS AND METHODS: The study sample consisted of 66 patients divided into UCLP (24 patients; mean age, 14.46 +/- 3.24 years), BCLP (17 patients; mean age, 14.28 +/- 2.85 years), and control (25 patients; mean age, 14.40 +/- 2.81 years) groups. The volume of the mandible including the condyle and the roots of the teeth and craniofacial measurements were performed using cone-beam computed tomography and analyzed using the one-way variance analysis and post hoc Tukey's tests. Regression analyses were used to evaluate the relationships of the measurements and the mandibular volume. RESULTS: Patients affected by UCLP and BCLP had similar craniofacial features (p > 0.05), including decreased SNB, Co-A, Co-Gn, Co-Go, and Go-Gn and increased ANB and SN-MP measurements compared to the control group. Both UCLP and BCLP groups had decreased values of mandibular volume compared to the normal occlusion group, while these differences were found to be statistically insignificant (p > 0.05). Co-Go (Beta = 0.420; p = 0.014) and Co-Gn variables (Beta = 0.708; p = 0.045) were positively correlated with mandibular volume, while SNB (Beta = -0.669; p = 0.044) and SN-MP (Beta = -0.358; p = 0.049) variables were negatively correlated (R (2) = 60.3 and p = 0.000). CONCLUSION: Mandibular volume insignificantly differs in cleft patients (p > 0.05), and the variables of Co-Go, Co-Gn, SNB, and SN-MP significantly correlate with the volume. CLINICAL RELEVANCE: This article investigates mandibular volume in patients affected by UCLP and BCLP that has never been investigated in the literature. The present study showed that both UCLP and BCLP groups had insignificantly decreased values of mandibular volume compared to the normal occlusion group. PMID- 26556575 TI - Involvement of oral tissues by AL amyloidosis: a literature review and report of eight new cases. AB - OBJECTIVE: Amyloidosis is a term used to describe a group of diseases in which there is an extracellular deposition of amorphous fibrillar proteins known as amyloid. The aim of this study was to present clinicopathological data from eight oral amyloidosis-affected patients and a deep review of the literature about the disease. MATERIALS AND METHODS: A retrospective study was conducted based on the records of oral amyloidosis-affected patients diagnosed in our institution between 1978 and 2012. The clinicopathological features and immunohistochemical (IHC) staining with anti-kappa and anti-lambda light chain antibodies were carried out and analyzed. RESULTS: Eight patients were diagnosed with the disease; the tongue and women in their sixth decade of life were mostly affected. All lesions demonstrated apple-green birefringence and immunoreactivity for kappa light chain, and four cases also showed lambda positivity. According to our series, four cases were diagnosed with localized amyloidosis and four with systemic amyloidosis. Prognosis for the systemic ones was gloomy, but good for the localized ones, which was characterized by a slow pattern of deposition without evolution to systemic involvement. CONCLUSIONS: This study reinforces our knowledge about predilections, outcomes, and the importance of making a correct and quick diagnosis of oral amyloidosis and shows the necessity of more studies detailing oral amyloidosis predilection on a global scale. The importance and utility of IHC in the typing of the biochemical nature of amyloid deposits are becoming increasingly necessary for proper management of the patient. Correct classification of the type of amyloid is important for treatment consequences. CLINICAL RELEVANCE: This article highlights the clinicopathological data of patients with amyloidosis affecting oral tissues and compare these new findings with other worldwide descriptions. Because of its rarity, such data are often unfamiliar to most clinicians and pathologists. PMID- 26556576 TI - Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs? AB - OBJECTIVES: The aim of this study was to investigate whether apical periodontitis (AP) could cause systemic cytokine elevation and pathological changes in remote organs in an experimental animal model. MATERIALS AND METHODS: AP was induced in 36 Sprague Dawley (SD) rats. Serum levels of C-reactive protein (CRP), interleukin 2 (IL-2), and interleukin 6 (IL-6) were measured by enzyme-linked immunosorbent assays at different time intervals (0, 6, 12, 24, 48, and 96 h and 1, 2, 3, 4, 5, and 6 weeks) after pulp exposure. Multiple organs (the aortic arch, myocardium, liver, and spleen) were collected for histological observation. The results were analyzed by one-way analysis of variance (ANOVA). RESULTS: Serum levels of CRP, IL-2, and IL-6 were significantly elevated at all time points assessed after 6, 24, and 96 h, respectively. The peak values of serum cytokines (CRP 6.363 +/- 0.05 ng/ml, IL-2 21.997 +/- 0.15 ng/L, and IL-6 2.406 +/- 0.02 ng/L) were reached at 1, 4, and 2 weeks, respectively, followed by a decline. Time-dependent reversible histopathological changes were detected in the aortic arch, myocardium, and spleen, whereas irreversible changes were found in the liver. CONCLUSIONS: AP elevated the levels of CRP, IL-2, and IL-6 in rat blood serum, causing reversible changes in the aortic arch, myocardium, and spleen as well as irreversible changes in the liver. CLINICAL RELEVANCE: AP may trigger a systemic immune response, impair remote organs, and affect the general health of patients. PMID- 26556577 TI - Enamel matrix protein derivative and/or synthetic bone substitute for the treatment of mandibular class II buccal furcation defects. A 12-month randomized clinical trial. AB - OBJECTIVE: This study aims to clinically evaluate the treatment of mandibular class II furcation defects with enamel matrix derivative (EMD) and/or a bone substitute graft made of beta-tricalcium phosphate/hydroxyapatite (betaTCP/HA). MATERIALS AND METHODS: Forty-one patients, presenting a mandibular class II buccal furcation defect, probing pocket depth (PPD) >=4 mm and bleeding on probing, were included. They were randomly assigned to the groups: 1-EMD (n = 13); 2-betaTCP/HA (n = 14); 3-EMD + betaTCP/HA (n = 14). Plaque index (PI), gingival index (GI), relative gingival margin position (RGMP), relative vertical and horizontal attachment level (RVCAL and RHCAL), and PPD were evaluated at baseline and 6 and 12 months. The mean horizontal clinical attachment level gain was considered the primary outcome variable. RESULTS: No significant intragroup differences were observed for RGMP, but significant changes were observed for RVCAL, RHCAL, and PPD for all groups (p < 0.05). After 12 months, the mean horizontal clinical attachment level gain was 2.77 +/- 0.93 mm for EMD, 2.64 +/- 0.93 mm for betaTCP/HA, and 2.93 +/- 0.83 mm for EMD + betaTCP/HA, with no significant differences among the groups. At the end of the study, 85.3 % of the sites were partially closed; however, no complete closure was observed. CONCLUSION: EMD + betaTCP/HA does not provide a significant advantage when compared to the isolated approaches. All three tested treatments promote significant improvements and partial closure of class II buccal furcation defects. Based on its potential to induce periodontal regeneration, EMD may be considered an attractive option for this type of defect, but complete closure remains an unrealistic goal. CLINICAL RELEVANCE: The partial closure of buccal furcation defects can be achieved after the three tested approaches. However, the combined treatment does not provide a significant benefit when compared to the isolated approaches. PMID- 26556578 TI - Evaluation of carbon nanotubes functionalized with sodium hyaluronate in the inflammatory processes for oral regenerative medicine applications. AB - OBJECTIVES: The objectives of this study were to assess the effects of hyaluronic acid (HY), multi-walled carbon nanotubes (MWCNT), and MWCNT functionalized with HY (HY-MWCNT) on the resolution of neutrophilic inflammation in the pleural cavity of LPS-challenged mice and to assess the influence of these materials in the inflammatory process of bone repair of tooth sockets of rats. MATERIALS AND METHODS: C57Bl/6 mice were intra-pleurally injected with HY, MWCNT, HY-MWCNT, phosphate-buffered saline (PBS), or LPS. The animals were euthanized after 8 and 24 h, and cells were harvested for total and differential cell counting. The tooth sockets of Wistar rats were filled with HY, MWCNT, HY-MWCNT, or blood clot (control). After 1, 3, and 7 days, histological and morphometric analyses evaluated the number of cell nuclei and blood vessels, and bone trabeculae formation in the sockets. Myeloperoxidase (MPO) activity quantified neutrophil accumulation in the sockets. RESULTS: HY, MWCNT, and HY-MWCNT increased neutrophilic recruitment at 8 h and reduced the inflammatory process at 24 h in the pleural cavity. Histological and morphometric analyses and MPO activity showed no significant differences in the recruitment of inflammatory cells in the tooth sockets. HY increased the number of blood vessels, and HY and HY-MWCNT increased bone trabeculae formation at 7 days of tooth extraction. CONCLUSIONS: HY, MWCNT, and HY-MWCNT resolved the neutrophilic inflammation in the pleural cavity of the mice. However, these materials did not modulate the inflammatory process in the early stages of bone repair of the tooth sockets, thereby excluding this action as a possible mechanism by which these biomaterials accelerate bone repair. CLINICAL RELEVANCE: HY-MWCNT is capable of accelerating bone repair/regeneration without affecting the inflammatory phase during the bone healing process. PMID- 26556579 TI - Enamel permeability and resistance to acid challenges after systemic use of sodium alendronate: a study in rat teeth. AB - OBJECTIVES: To evaluate the enamel resistance and permeability of rat teeth to acid challenges after systemic use of sodium alendronate. MATERIALS AND METHODS: Eighteen Wistar rats (36 teeth), aged 36-42 days (200-230 g), were assigned into two groups: alendronate group (n = 20 teeth), which received two weekly doses of 1 mg/kg of alendronate, via gavage; and a non-alendronate group (n = 16 teeth), which received only distilled water. After 60 days, the animals were killed, the maxillary incisors were extracted and used for the artificial induction of the caries lesion (pH cycling regimen) and erosion area (immersion cycles in cola type soft drink) and for the enamel permeability test (dye penetration). The teeth were divided into alendronate group (n = 10) or non-alendronate group (n = 8) for each test. The quantitative response variables were the percent longitudinal change in Knoop microhardness (%LMC), the enamel carious/erosion lesion area (CELA) and enamel permeability. RESULTS: Groups were not significantly different (p > 0.05) with regard to the %LMC and enamel permeability (25.58 MUm +/- 12.73 and 25.40 MUm +/- 4.6 for the experimental and control groups, respectively). For CELA, it was not observed significant difference (p > 0.05) between the non-alendronate group (24.08 +/- 1.36 and 25.22 +/- 1.60, for caries and erosion, respectively) and the alendronate group (25.46 +/- 1.60 and 25.0 +/- 1.26) for caries and erosion, respectively). CONCLUSIONS: Based on the methodological conditions and the presented results of this study, sodium alendronate did not affect the longitudinal microhardness, demineralisation lesion area or permeability of the enamel after acid challenge; therefore, alendronate did not become the enamel of rats more resistant. CLINICAL RELEVANCE: The systemic alendronate treatment for 60 days did not change the enamel of rats regarding the susceptibility to acids. PMID- 26556580 TI - What factors influence the choice of urban or rural location for future practice of Nepalese medical students? A cross-sectional descriptive study. AB - BACKGROUND: Nepal is experiencing a public health issue similar to the rest of the world, i.e., the geographical maldistribution of physicians. Although there is some documentation about the reasons physicians elect to leave Nepal to work abroad, very little is known about the salient factors that influence the choice of an urban versus rural practice setting for those physicians who do not migrate. In recent years, around 1000 medical students became doctors within Nepal, but their distribution in rural locations is not adequate. The purpose of this study was to explore what factors influence the choice of urban or rural location for the future clinical practice of Nepalese medical students in the final year of their program METHODS: A cross-sectional descriptive study design was used for this study involving Nepalese medical students in their final year of study and currently doing an internship in a medical college. The sample consisted of 393 medical students from four medical colleges in Nepal that were selected randomly. An anonymous self-administered questionnaire was used for data collection. To determine the association with rural location choice for their future practice setting, a comparison was done that involved demographic, socio economic, and educational factors. Data were entered in EpiData and analyzed by using SPSS version 16. RESULTS: Among the 393 respondents, two thirds were male (66.9%) and more than half were below 25 years of age. Almost all (93%) respondents were single and about two thirds (63.4%) were of Brahmin and Chhetri ethnic origin. About two thirds (64.1%) of the respondents were born in a rural setting, and 58.8% and 53.3% had a place of rearing and permanent address in a rural location, respectively. The predictors of future rural location choice for their clinical practice (based on the bivariate analysis) included: (a) Rural (versus urban) place of birth, place of rearing, and permanent address (b) Source of family income (service, business, and agriculture) (c) Occupation of father (service, business and agriculture) (d) Wealth ranking (higher, middle, and lower wealth rank) (e) Educational factors: location, type of secondary education, and type of higher secondary education. CONCLUSION: For medical students who were soon to complete their studies, demographic and educational factors were found to be significant predictors for a rural location choice, as opposed to socio economic factors. Our findings indicate that to ensure the rural retention of physicians, the government of Nepal should attract potential medical students from those who were reared and educated in a rural setting. PMID- 26556581 TI - Implications of Climate Change on the Heat Budget of Lentic Systems Used for Power Station Cooling: Case Study Clinton Lake, Illinois. AB - We use a numerical model to analyze the impact of climate change-in particular higher air temperatures-on a nuclear power station that recirculates the water from a reservoir for cooling. The model solves the hydrodynamics, the transfer of heat in the reservoir, and the energy balance at the surface. We use the numerical model to (i) quantify the heat budget in the reservoir and determine how this budget is affected by the combined effect of the power station and climate change and (ii) quantify the impact of climate change on both the downstream thermal pollution and the power station capacity. We consider four different scenarios of climate change. Results of simulations show that climate change will reduce the ability to dissipate heat to the atmosphere and therefore the cooling capacity of the reservoir. We observed an increase of 25% in the thermal load downstream of the reservoir, and a reduction in the capacity of the power station of 18% during the summer months for the worst-case climate change scenario tested. These results suggest that climate change is an important threat for both the downstream thermal pollution and the generation of electricity by power stations that use lentic systems for cooling. PMID- 26556582 TI - Triggered Excited-State Intramolecular Proton Transfer Fluorescence for Selective Triplex DNA Recognition. AB - The triplex DNA has received much interest due to its various applications in gene regulation, molecular switch, and sensor development. However, realizing a highly selective recognition using a fluorescence probe specific only for the triplex topology is still a great challenge. Herein, we found that relative to the structural analogues of natural robinetin, myricetin, quercetin, kaempferol, morin, rutin, baicalin, luteolin, naringenin, genistein, chrysin, galangin, isorhamnetin, and several synthetic flavonoids, fisetin (FIS) is the brightest emitter when targeting the triplex DNA in contrast to binding with ss-DNA, ds-DNA (with or without an abasic site), i-motif, and DNA/RNA G-quadruplexes. Only the triplex association triggers the FIS green fluorescence that is relaxed from the tautomer favorable for excited-state intramolecular proton transfer (ESIPT). FIS can stabilize the triplex structure and primarily interact with the two terminals of the triplex via a 2:1 binding mode. This work demonstrates the potential of FIS as a DNA structure-selective switch-on ESIPT probe when evolving the triplex forming oligonucleotides and developing the novel triplex-based sensors and switches. PMID- 26556583 TI - Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale. AB - Azacitidine is a mainstay for treating hematological disorders. Azacitidine is metabolized by cytidine deaminase, coded by a highly polymorphic gene. Here, we present two elderly patients with opposite clinical outcomes after azacitidine treatment. First, an acute myeloid leukemia patient showed life-threatening toxicities, but outstanding complete remission, after a single round of azacitidine. Further investigations showed that this patient was cytidine deaminase 79A>C (rs2072671) homozygous with a marked deficient phenotype. Next, a chronic myelomonocytic leukemia patient displayed complete lack of response despite several cycles of azacitidine. This patient had a rapid-deaminator phenotype linked to the -31delC deletion (rs3215400). These polymorphisms lead to opposite clinical outcomes in patients with myelodysplastic syndromes treated with azacitidine, thus suggesting that determining cytidine deaminase status could help to forecast clinical outcome. PMID- 26556584 TI - A SERS Study on the Assembly Behavior of Gold Nanoparticles at the Oil/Water Interface. AB - Herein, the assembly behavior of gold nanoparticles (AuNPs) at the oil/water interface is studied by surface-enhanced Raman scattering (SERS) spectroscopy. Two selected chemicals [1-dodecanethiol (DDT) and tetramethylammonium ion (TMA(+))] are applied to tune the surface properties of AuNPs and the corresponding assembly behaviors at the oil/water interface are thoroughly investigated. Various AuNPs films, namely sparse 2D film, perfect monolayer, and multilayers are obtained. The SERS spectra analyses show that the surface composition of AuNPs is strongly dependent on the chemical environment around AuNPs and results in different morphologies of AuNPs film at the oil/water interface. Accordingly, we propose a rational relationship between AuNPs assembly behavior at the oil/water interface and their surrounding chemical environment, and thus reveals the physical mechanism underlying the nanoparticle assembly. PMID- 26556585 TI - Surgical treatment of paediatric nail bed injuries in the United Kingdom: Surgeon and patient priorities for future research. PMID- 26556586 TI - Comparison between eyelid indices of ptotic eye and normal fellow eye in patients with unilateral congenital ptosis. AB - PURPOSE: To evaluate the relationship between levator muscle function (LMF) and other eyelid parameters in the normal and affected eyes of patients with unilateral congenital ptosis. METHODS: This study includes subjects with unilateral congenital upper lid ptosis who were referred for operation over a 2 year period. Patients with other eyelid abnormalities and previous eyelid surgery were excluded. Eyelid parameters including LMF, lid fissure height (LFH) and margin reflex distance (MRD) were measured in both eyes and analyzed. RESULTS: A total of 77 patients with mean age of 26.4 +/- 16.4 years were enrolled in the study. Mean LMF was 8.3 +/- 4.6 mm in the ptotic and 13.1 +/- 3.6 mm in the normal fellow eyes. Each millimeter of difference in LMF was associated with 0.30 mm of difference in LFH (95% CI: 0.25-0.35, P < 0.001) and 0.11 mm of difference in MRD of the ptotic eyes (95% CI: 0.08-0.12, P < 0.001) in the same direction. In addition, each millimeter of difference in LMF of ptotic eyes was associated with 0.48 mm of difference (95% CI: 0.33-0.62, P < 0.001) in LMF of non-ptotic eyes in the same direction. CONCLUSION: A direct correlation was observed between LMF, and LFH and MRD in ptotic eyes which confirms the role of levator muscle dysfunction in the development of congenital ptosis and its severity. Furthermore, a direct correlation was also present between LMF of ptotic and non ptotic eyes suggesting possible bilateral involvement in apparently unilateral congenital ptosis. PMID- 26556587 TI - Re: 'Dynamic reconstruction of complex abdominal wall defects with the pedicled innervated vastus lateralis and anterolateral thigh PIVA flap'. PMID- 26556588 TI - Helicobacter cinaedi bacteremia in four renal transplant patients: clinical features and an important suggestion regarding the route of infection. AB - Helicobacter cinaedi can cause bacteremia mainly in immunocompromised patients. We present the clinical characteristics of H. cinaedi bacteremia in 4 renal transplant patients. Interestingly, all cases showed triggers of bacterial translocation: 2 cases developed after colonic perforation caused by diverticulitis, 1 case developed post cholecystectomy, and the remaining patient had chronic diarrhea. Accordingly, bacterial translocation caused by severe gastrointestinal complication could be a cause of H. cinaedi bacteremia. PMID- 26556589 TI - Does type 1 diabetes mellitus affect Achilles tendon response to a 10 km run? A case control study. AB - BACKGROUND: Achilles tendon structure deteriorates 2-days after maximal loading in elite athletes. The load-response behaviour of tendons may be altered in type 1 diabetes mellitus (T1DM) as hyperglycaemia accelerates collagen cross-linking. This study compared Achilles tendon load-response in participants with T1DM and controls. METHODS: Achilles tendon structure was quantified at day-0, day-2 and day-4 after a 10 km run. Ultrasound tissue characterisation (UTC) measures tendon structural integrity by classifying pixels as echo-type I, II, III or IV. Echo type I has the most aligned collagen fibrils and IV has the least. RESULTS: Participants were 7 individuals with T1DM and 10 controls. All regularly ran distances greater than 5 km and VISA-A scores indicated good tendon function (T1DM = 94 +/- 11, control = 94 +/- 10). There were no diabetic complications and HbA1c was 8.7 +/- 2.6 mmol/mol for T1DM and 5.3 +/- 0.4 mmol/mol for control groups. Baseline tendon structure was similar in T1DM and control groups - UTC echo-types (I-IV) and anterior-posterior thickness were all p > 0.05. No response to load was seen in either T1DM or control group over the 4-days post exercise. CONCLUSION: Active individuals with T1DM do not have a heightened Achilles tendon response to load, which suggests no increased risk of tendon injury. We cannot extrapolate these findings to sedentary individuals with T1DM. PMID- 26556590 TI - Evolutionary Rate Heterogeneity of Primary and Secondary Metabolic Pathway Genes in Arabidopsis thaliana. AB - Primary metabolism is essential to plants for growth and development, and secondary metabolism helps plants to interact with the environment. Many plant metabolites are industrially important. These metabolites are produced by plants through complex metabolic pathways. Lack of knowledge about these pathways is hindering the successful breeding practices for these metabolites. For a better knowledge of the metabolism in plants as a whole, evolutionary rate variation of primary and secondary metabolic pathway genes is a prerequisite. In this study, evolutionary rate variation of primary and secondary metabolic pathway genes has been analyzed in the model plant Arabidopsis thaliana. Primary metabolic pathway genes were found to be more conserved than secondary metabolic pathway genes. Several factors such as gene structure, expression level, tissue specificity, multifunctionality, and domain number are the key factors behind this evolutionary rate variation. This study will help to better understand the evolutionary dynamics of plant metabolism. PMID- 26556591 TI - The X Chromosome of Hemipteran Insects: Conservation, Dosage Compensation and Sex Biased Expression. AB - Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/X0 system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order.In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order. PMID- 26556592 TI - The in vitro antioxidant properties of alcalase hydrolysate prepared from silkie fowl (Gallus gallus) blood protein. AB - Two types of proteins including blood plasma protein and blood cell protein were isolated from silkie fowl (Gallus gallus) blood and hydrolyzed using alcalase for 0, 2, 4 and 6 h. The blood plasma protein hydrolysate (BPH) and blood cell protein hydrolysate (BCH) were analyzed for pH value, peptide content and antioxidative properties. The significantly higher peptide contents were observed in BPH than that of BCH, which showed that blood plasma protein was more suitable to hydrolysis by alcalase than blood cell protein. Both BPH and BCH showed strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and Fe(2+) chelating ability. BPH at 4 h of hydrolysis (BPH4) demonstrated significantly higher antioxidant capacity than those treated by alcalase in most of the assays. The BPH4 was separated using ultra-filtration and assessment of the fractions and indicated that low molecular weight of peptides (< 3 kDa) possessed greater DPPH scavenging activity, Fe(2+) chelating ability and inhibitory activity of lipid peroxidation. These results show that BPH has the potential to be ingredients in the food industry as a replacement of synthetic antioxidants. PMID- 26556593 TI - An Aqueous Two-Phase System for the Concentration and Extraction of Proteins from the Interface for Detection Using the Lateral-Flow Immunoassay. AB - The paper-based immunoassay for point-of-care diagnostics is widely used due to its low cost and portability over traditional lab-based assays. Lateral-flow immunoassay (LFA) is the most well-established paper-based assay since it is rapid and easy to use. However, the disadvantage of LFA is its lack of sensitivity in some cases where a large sample volume is required, limiting its use as a diagnostic tool. To improve the sensitivity of LFA, we previously reported on the concentration of analytes into one of the two bulk phases of an aqueous two-phase system (ATPS) prior to detection. In this study, we preserved the advantages of LFA while significantly improving upon our previous proof-of concept studies by employing a novel approach of concentrating gold nanoparticles, a common LFA colorimetric indicator. By conjugating specific antibodies and polymers to the surfaces of the particles, these gold nanoprobes (GNPs) were able to capture target proteins in the sample and subsequently be concentrated within 10 min at the interface of an ATPS solution comprised of polyethylene glycol, potassium phosphate, and phosphate-buffered saline. These GNPs were then extracted and applied directly to LFA. By combining this prior ATPS interface extraction with LFA, the detection limit of LFA for a model protein was improved by 100-fold from 1 ng/MUL to 0.01 ng/MUL. Additionally, we examined the behavior of the ATPS system in fetal bovine serum and synthetic urine to more closely approach real-world applications. Despite using more complex matrices, ATPS interface extraction still improved the detection limit by 100-fold within 15 to 25 min, demonstrating the system's potential to be applied to patient samples. PMID- 26556594 TI - Implementation Science Workshop: Implementation of an Electronic Referral System in a Large Academic Medical Center. PMID- 26556596 TI - [Knee prosthetic-joint infection due to Mycobacterium fortuitum]. PMID- 26556595 TI - Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate. AB - Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes. PMID- 26556597 TI - Comparison of the Cowpox Virus and Vaccinia Virus Mature Virion Proteome: Analysis of the Species- and Strain-Specific Proteome. AB - Cowpox virus (CPXV) causes most zoonotic orthopoxvirus (OPV) infections in Europe and Northern as well as Central Asia. The virus has the broadest host range of OPV and is transmitted to humans from rodents and other wild or domestic animals. Increasing numbers of human CPXV infections in a population with declining immunity have raised concerns about the virus' zoonotic potential. While there have been reports on the proteome of other human-pathogenic OPV, namely vaccinia virus (VACV) and monkeypox virus (MPXV), the protein composition of the CPXV mature virion (MV) is unknown. This study focused on the comparative analysis of the VACV and CPXV MV proteome by label-free single-run proteomics using nano liquid chromatography and high-resolution tandem mass spectrometry (nLC-MS/MS). The presented data reveal that the common VACV and CPXV MV proteome contains most of the known conserved and essential OPV proteins and is associated with cellular proteins known to be essential for viral replication. While the species-specific proteome could be linked mainly to less genetically-conserved gene products, the strain-specific protein abundance was found to be of high variance in proteins associated with entry, host-virus interaction and protein processing. PMID- 26556599 TI - Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia. AB - BACKGROUND: Deletion of the late cornified envelope (LCE) proteins LCE3B and LCE3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis-specific proteins, rather than being a single-nucleotide polymorphism of uncertain significance. The biology of the 18-member LCE family of highly homologous proteins has remained largely unexplored so far. OBJECTIVES: To analyse LCE3 expression at the protein level in human epithelia, as a starting point for functional analyses of these proteins in health and disease. METHODS: We generated the first pan-LCE3 monoclonal antibody and provide a detailed analysis of its specificity towards individual LCE members. LCE2 and LCE3 expression in human tissues and in reconstructed human skin models was studied using immunohistochemical analyses and quantitative polymerase chain reaction. RESULTS: Our study reveals that LCE2 and LCE3 proteins are differentially expressed in human epidermis, and colocalize only in the upper stratum granulosum layer. Using an in vitro reconstructed human skin model that mimics epidermal morphogenesis, we found that LCE3 proteins are expressed at an early time point during epidermal differentiation in the suprabasal layers, while LCE2 proteins are found only in the uppermost granular layer and stratum corneum. CONCLUSIONS: Based on the localization of LCE2 and LCE3 in human epidermis we conclude that members of the LCE protein family are likely to have distinct functions in epidermal biology. This finding may contribute to understanding why LCE3B/C deletion increases psoriasis risk. PMID- 26556598 TI - Associations of Body Composition Measurements with Serum Lipid, Glucose and Insulin Profile: A Chinese Twin Study. AB - OBJECTIVES: To quantitate and compare the associations of various body composition measurements with serum metabolites and to what degree genetic or environmental factors affect obesity-metabolite relation. METHODS: Body mass index (BMI), waist circumference (WC), lean body mass (LBM), percent body fat (PBF), fasting serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), glucose, insulin and lifestyle factors were assessed in 903 twins from Chinese National Twin Registry (CNTR). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting serum glucose and insulin. Linear regression models and bivariate structural equation models were used to examine the relation of various body composition measurements with serum metabolite levels and genetic/environmental influences on these associations, respectively. RESULTS: At individual level, adiposity measurements (BMI, WC and PBF) showed significant associations with serum metabolite concentrations in both sexes and the associations still existed in male twins when using within-MZ twin pair comparison analyses. Associations of BMI with TG, insulin and HOMA-IR were significantly stronger in male twins compared to female twins (BMI-by-sex interaction p = 0.043, 0.020 and 0.019, respectively). Comparison of various adiposity measurements with levels of serum metabolites revealed that WC explained the largest fraction of variance in serum LDL-C, TG, TC and glucose concentrations while BMI performed best in explaining variance in serum HDL-C, insulin and HOMA-IR levels. Of these phenotypic correlations, 64-81% were attributed to genetic factors, whereas 19-36% were attributed to unique environmental factors. CONCLUSIONS: We observed different associations between adiposity and serum metabolite profile and demonstrated that WC and BMI explained the largest fraction of variance in serum lipid profile and insulin resistance, respectively. To a large degree, shared genetic factors contributed to these associations with the remaining explained by twin-specific environmental factors. PMID- 26556600 TI - dTAF10- and dTAF10b-Containing Complexes Are Required for Ecdysone-Driven Larval Pupal Morphogenesis in Drosophila melanogaster. AB - In eukaryotes the TFIID complex is required for preinitiation complex assembly which positions RNA polymerase II around transcription start sites. On the other hand, histone acetyltransferase complexes including SAGA and ATAC, modulate transcription at several steps through modification of specific core histone residues. In this study we investigated the function of Drosophila melanogaster proteins TAF10 and TAF10b, which are subunits of dTFIID and dSAGA, respectively. We generated a mutation which eliminated the production of both Drosophila TAF10 orthologues. The simultaneous deletion of both dTaf10 genes impaired the recruitment of the dTFIID subunit dTAF5 to polytene chromosomes, while binding of other TFIID subunits, dTAF1 and RNAPII was not affected. The lack of both dTAF10 proteins resulted in failures in the larval-pupal transition during metamorphosis and in transcriptional reprogramming at this developmental stage. Surprisingly, unlike dSAGA mutations, dATAC subunit mutations resulted in very similar changes in the steady state mRNA levels of approximately 5000 genes as did ablation of both dTaf10 genes, indicating that dTAF10- and/or dTAF10b-containing complexes and dATAC affect similar pathways. Importantly, the phenotype resulting from dTaf10+dTaf10b mutation could be rescued by ectopically added ecdysone, suggesting that dTAF10- and/or dTAF10b-containing complexes are involved in the expression of ecdysone biosynthetic genes. Indeed, in dTaf10+dTaf10b mutants, cytochrome genes, which regulate ecdysone synthesis in the ring gland, were underrepresented. Therefore our data support the idea that the presence of dTAF10 proteins in dTFIID and/or dSAGA is required only at specific developmental steps. We propose that distinct forms of dTFIID and/or dSAGA exist during Drosophila metamorphosis, wherein different TAF compositions serve to target RNAPII at different developmental stages and tissues. PMID- 26556601 TI - The Effects of Extracorporeal Shock Wave Therapy in Patients with Coccydynia: A Randomized Controlled Trial. AB - Coccydynia is pain in the coccygeal region, and usually treated conservatively. Extracorporeal shock wave therapy (ESWT) was incorporated as non-invasive treatment of many musculoskeletal conditions. However, the effects of ESWT on coccydynia are less discussed. The purpose of this study is to evaluate the effects of ESWT on the outcomes of coccydynia. Patients were allocated to ESWT (n = 20) or physical modality (SIT) group (n = 21) randomly, and received total treatment duration of 4 weeks. The visual analog scale (VAS), Oswestry disability index (ODI), and self-reported satisfaction score were used to assess treatment effects. The VAS and ODI scores were significantly decreased after treatment in both groups, and the decrease in the VAS score was significantly greater in the ESWT group. The mean proportional changes in the ODI scores were greater in the ESWT group than in the SIT group, but the between-group difference was not statistically significant. The patients in the ESWT group had significantly higher subjective satisfaction scores than SIT group. We concluded that ESWT is more effective and satisfactory in reducing discomfort and disability caused by coccydynia than the use of physical modalities. Thus, ESWT is recommended as an alternative treatment option for patients with coccydynia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02313324. PMID- 26556602 TI - Inflammatory potential of diet and risk for hepatocellular cancer in a case control study from Italy. AB - Inflammation and diet have been suggested to be important risk factors for hepatocellular cancer (HCC). This Italian multicentre hospital-based case-control study conducted between 1999 and 2002 and including 185 cases with incident, histologically confirmed HCC, and 404 controls hospitalised for acute non neoplastic diseases provided an opportunity to investigate the association between HCC and the dietary inflammatory index (DII). The DII was computed on the basis of dietary intake assessed 2 years before the date of interview by a validated sixty-three-item FFQ. Logistic regression models were used to estimate OR adjusted for age, sex, study centre, education, BMI, smoking, physical activity, serum markers of hepatitis B and C infection and energy intake. Energy adjustment for DII was performed using the residual method. Participants in the highest tertile of DII scores (i.e. with a more pro-inflammatory diet) had a higher risk for HCC (ORtertile 3 v, 1 2.43; 95 % CI 1.27, 4.68; P trend=0.03). When stratified by the presence or absence of hepatitis B/C infection and sex, DII was strongly associated with HCC in hepatitis B- and C-negative participants (ORtertile 3 v. 1 4.18; 95 % CI 1.53, 11.39; P trend=0.02) and among males (ORtertile 3 v. 1 3.60; 95 % CI 1.65, 7.87; P trend=0.001). These results indicate that a pro-inflammatory diet is associated with increased risk for HCC, in those without a history of hepatitis B/C infection and among males. PMID- 26556603 TI - A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis. AB - Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84 but was not consistently in agreement with PASI. Improvement in histology was associated with modulation of IL-17 and TNF-alpha signaling pathways and keratinocyte differentiation target genes. 27 subjects (69%) across all treatment groups, including placebo, experienced at least one treatment emergent adverse event. The majority of AEs were either mild or moderate. Most common were headache (8%), dizziness (8%), upper respiratory tract infection (8%), and psoriatic arthropathy (8%). Average drug exposure increased in a dose-dependent manner for escalating doses of SRT2104 and had high intra-subject variability in exposure (AUC %CV: 51-89%). Given the interesting signals of clinical activity, impact on gene expression and the generally favorable safety profile seen in this study, further investigation of SIRT1 activators for the treatment of psoriasis is warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT01154101. PMID- 26556604 TI - Probing the effects of 2D confinement on hydrogen dynamics in water and ice adsorbed in graphene oxide sponges. AB - We studied the single particle dynamics of water and ice adsorbed in graphene oxide (GO) sponges at T = 293 K and T = 20 K. We used Deep Inelastic Neutron Scattering (DINS) at the ISIS neutron and muon spallation source to derive the hydrogen mean kinetic energy, , and momentum distribution, n(p). The goal of this work was to study the hydrogen dynamics under 2D confinement and the potential energy surface, fingerprinting the hydrogen interaction with the layered structure of the GO sponge. The observed scattering is interpreted within the framework of the impulse approximation. Samples of both water and ice adsorbed in GO show n(p) functions with almost harmonic and anisotropic line shapes and values in excess of the values found at the corresponding temperatures in the bulk. The hydrogen dynamics are discussed in the context of the interaction between the interfacial water and ice and the confining hydrophilic surface of the GO sponge. PMID- 26556606 TI - Importance of the Electron Correlation and Dispersion Corrections in Calculations Involving Enamines, Hemiaminals, and Aminals. Comparison of B3LYP, M06-2X, MP2, and CCSD Results with Experimental Data. AB - While B3LYP, M06-2X, and MP2 calculations predict the DeltaG degrees values for exchange equilibria between enamines and ketones with similar acceptable accuracy, the M06-2X/6-311+G(d,p) and MP2/6-311+G(d,p) methods are required for enamine formation reactions (for example, for enamine 5a, arising from 3 methylbutanal and pyrrolidine). Stronger disagreement was observed when calculated energies of hemiaminals (N,O-acetals) and aminals (N,N-acetals) were compared with experimental equilibrium constants, which are reported here for the first time. Although it is known that the B3LYP method does not provide a good description of the London dispersion forces, while M06-2X and MP2 may overestimate them, it is shown here how large the gaps are and that at least single-point calculations at the CCSD(T)/6-31+G(d) level should be used for these reaction intermediates; CCSD(T)/6-31+G(d) and CCSD(T)/6-311+G(d,p) calculations afford DeltaG degrees values in some cases quite close to MP2/6-311+G(d,p) while in others closer to M06-2X/6-311+G(d,p). The effect of solvents is similarly predicted by the SMD, CPCM, and IEFPCM approaches (with energy differences below 1 kcal/mol). PMID- 26556605 TI - Wheat germ-based protein libraries for the functional characterisation of the Arabidopsis E2 ubiquitin conjugating enzymes and the RING-type E3 ubiquitin ligase enzymes. AB - BACKGROUND: Protein ubiquitination is a ubiquitous mechanism in eukaryotes. In Arabidopsis, ubiquitin modification is mainly mediated by two ubiquitin activating enzymes (E1s), 37 ubiquitin conjugating enzymes (E2s), and more than 1300 predicted ubiquitin ligase enzymes (E3s), of which ~470 are RING-type E3s. A large proportion of the RING E3's gene products have yet to be characterised in vitro, likely because of the laborious work involved in large-scale cDNA cloning and protein expression, purification, and characterisation. In addition, several E2s, which might be necessary for the activity of certain E3 ligases, cannot be expressed by Escherichia coli or cultured insect cells and, therefore, remain uncharacterised. RESULTS: Using the RIKEN Arabidopsis full-length cDNA library (RAFL) with the 'split-primer' PCR method and a wheat germ cell-free system, we established protein libraries of Arabidopsis E2 and RING E3 enzymes. We expressed 35 Arabidopsis E2s including six enzymes that have not been previously expressed, and 204 RING proteins, most of which had not been functionally characterised. Thioester assays using dithiothreitol (DTT) showed DTT-sensitive ubiquitin thioester formation for all E2s expressed. In expression assays of RING proteins, 31 proteins showed high molecular smears, which are probably the result of their functional activity. The activities of another 27 RING proteins were evaluated with AtUBC10 and/or a group of different E2s. All the 27 RING E3s tested showed ubiquitin ligase activity, including 17 RING E3s. Their activities are reported for the first time. CONCLUSION: The wheat germ cell-free system used in our study, which is a eukaryotic expression system and more closely resembles the endogenous expression of plant proteins, is very suitable for expressing Arabidopsis E2s and RING E3s in their functional form. In addition, the protein libraries described here can be used for further understanding E2-E3 specificities and as platforms for protein-protein interaction screening. PMID- 26556608 TI - Correction: Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo. PMID- 26556607 TI - In Vivo Therapeutic Success of MicroRNA-155 Antagomir in a Mouse Model of Lupus Alveolar Hemorrhage. AB - OBJECTIVE: Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Pristane-treated B6 mice develop severe DAH within 2 weeks of treatment. MicroRNA-155 (miR-155) is a pleiotropic microRNA that plays a crucial role in the regulation of immune responses. Recent studies have revealed a pathogenic role of miR-155 in various autoimmune disorders. The purpose of this study was to examine the role of miR 155 in the development of DAH in pristane-induced lupus using miR-155-knockout (miR-155(-/-)) mice and miR-155 antagomir to silence miR-155. METHODS: DAH was induced by an intraperitoneal injection of 0.5 ml of pristane. MicroRNA-155 antagomir was administered intravenously to silence miR-155 expression. Lung tissues were collected for RNA extraction and were embedded in paraffin for sectioning. Gene expression profiling data were analyzed using Ingenuity Pathway Analysis. Real-time quantitative polymerase chain reaction analysis was used for single-gene validation. Luciferase reporter assay and argonaute 2 immunoprecipitation were performed for target validation. RESULTS: MicroRNA-155 expression was significantly increased during the development of DAH. Disease progression was reduced in miR-155(-/-) mice as well as by in vivo silencing of miR-155 using a miR-155 antagomir. MicroRNA-155 silencing dampened pristane induced ectopic activation of multiple inflammatory pathways and reduced the expression of proinflammatory cytokines. Several negative regulators of NF-kappaB signaling were inhibited by pristane and were reactivated in miR-155(-/-) mice. In particular, the antiinflammatory factor peroxisome proliferator-activated receptor alpha was identified as a direct target of miR-155. CONCLUSION: MicroRNA 155 promotes pristane-induced lung inflammation. It contributes to ectopic activation of NF-kappaB signaling pathways by targeting multiple negative regulators. MicroRNA-155 antagomir may be a promising therapeutic strategy for treating acute lung inflammation in lupus. PMID- 26556609 TI - The genomics of ecological vicariance in threespine stickleback fish. AB - Populations occurring in similar habitats and displaying similar phenotypes are increasingly used to explore parallel evolution at the molecular level. This generally ignores the possibility that parallel evolution can be mimicked by the fragmentation of an ancestral population followed by genetic exchange with ecologically different populations. Here we demonstrate such an ecological vicariance scenario in multiple stream populations of threespine stickleback fish divergent from a single adjacent lake population. On the basis of demographic and population genomic analyses, we infer the initial spread of a stream-adapted ancestor followed by the emergence of a lake-adapted population, that selective sweeps have occurred mainly in the lake population, that adaptive lake-stream divergence is maintained in the face of gene flow from the lake into the streams, and that this divergence involves major inversion polymorphisms also important to marine-freshwater stickleback divergence. Overall, our study highlights the need for a robust understanding of the demographic and selective history in evolutionary investigations. PMID- 26556610 TI - Optimizing apnea testing to determine brain death. PMID- 26556612 TI - Cardiac luxation in ICU after coughing effort following right pneumonectomy. PMID- 26556611 TI - Apnea test during brain death assessment in mechanically ventilated and ECMO patients. AB - PURPOSE: To evaluate the feasibility and efficacy of an apnea test (AT) technique that combines the application of positive end expiratory pressure (PEEP) with subsequent pulmonary recruitment in a large cohort of brain-dead patients. METHODS: This study was a retrospective analysis of prospectively collected data on brain-dead patients admitted to our institution (Hospital San Gerardo, Monza, Italy) between January 2010 and December 2014. The rate of aborted apnea tests (ATs), occurrence of complications (i.e., pneumothorax, cardiac arrhythmias, cardiac arrest, and severe hypoxia, defined as PaO2 < 40 mmHg), ventilator settings, hemodynamics, and blood gas analyses were evaluated. Subgroup analysis was performed, with patients classified into veno-arterial extracorporeal membrane oxygenation (ECMO) or non-ECMO groups, and into hypoxic (i.e., baseline PaO2/FiO2 < 200 mmHg) and non-hypoxic (i.e., baseline PaO2/FiO2 > 200 mmHg) groups. RESULTS: In total, 169 consecutive patients including 25 on ECMO were included in the study. No AT abortion nor severe complications were detected. The AT was completed in all patients. Fluid boluses and increases or initiation of vasoactive drugs were required in less than 10 and 3% of the AT procedures, respectively. No clinically meaningful alteration in hemodynamics was recorded. Severe hypoxia occurred during 7 (2.4%) and 4 (8%) of the ATs performed in non ECMO and ECMO patients, respectively (p = 0.063), and it occurred more frequently in hypoxic patients than in non-hypoxic patients (11.1 vs. 4.8%, respectively; p = 0.002). CONCLUSIONS: In a large cohort of consecutive patients, including the largest patient population on ECMO reported to date, our AT technique that combines the application of PEEP with subsequent pulmonary recruitment proved to be feasible and safe. PMID- 26556613 TI - Cardiac effect of sodium bicarbonate in sodium-channel blocker poisoning. PMID- 26556614 TI - "Does this patient have..." "Is this patient at risk for infection with multidrug resistant bacteria?" PMID- 26556615 TI - Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. AB - INTRODUCTION: Current clinical practice guidelines recommend providing ICU patients a daily caloric intake estimated to match 80-100 % of energy expenditure (normocaloric goals). However, recent clinical trials of intentional hypocaloric feeding question this approach. METHODS: We performed a systematic review and meta-analysis to compare the outcomes of ICU patients randomized to intentional hypocaloric or normocaloric goals. We included randomized controlled trials that enrolled ICU patients and compared intentional hypocaloric with normocaloric nutritional goals. We included studies that evaluated both trophic feeding as well as permissive underfeeding. Data sources included MEDLINE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. The outcomes of interest included hospital acquired infection, hospital mortality, ICU length of stay (LOS) and ventilator-free days (VFDs). RESULTS: Six studies which enrolled 2517 patients met our inclusion criteria. The mean age and body mass index (BMI) across the studies were 53 +/- 5 years and 29.1 +/- 1.5 kg/m(2), respectively. Two studies compared normocaloric feeding (77% of goal) with trophic feeding (20% of goal), while four studies compared normocaloric feeding (72% of goal) with permissive underfeeding (49% of goal). Overall, there was no significant difference in the risk of infectious complications (OR 1.03; 95% CI 0.84-1.27, I(2) = 16%), hospital mortality (OR 0.91; 95% CI 0.75-1.11, I(2) = 8%) or ICU LOS (mean difference 0.05 days; 95% CI 1.33-1.44 days; I(2) = 37%) between groups. VFDs were reported in three studies with no significant difference between the normocaloric and intentional hypocaloric groups (data not pooled). CONCLUSION: This meta-analysis demonstrated no difference in the risk of acquired infections, hospital mortality, ICU length of stay or ventilator-free days between patients receiving intentional hypocaloric as compared to normocaloric nutritional goals. PMID- 26556616 TI - Night shift decreases cognitive performance of ICU physicians. AB - BACKGROUND: The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated. METHODS: A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. RESULTS: All cognitive abilities worsened after a night shift: working memory capacity (11.3 +/- 0.3 vs. 9.4 +/- 0.3; p < 0.001), speed of processing information (13.5 +/- 0.4 vs. 10.9 +/- 0.3; p < 0.001), perceptual reasoning (10.6 +/- 0.3 vs. 9.3 +/- 0.3; p < 0.002), and cognitive flexibility (41.2 +/- 1.2 vs. 44.2 +/- 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift. CONCLUSIONS: The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients' safety and physicians' health should be further evaluated. PMID- 26556617 TI - Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. AB - PURPOSE: Hyperlactatemia may occur for a variety of reasons and is a predictor of poor clinical outcome. However, only limited data are available on the underlying causes of hyperlactatemia and the mortality rates associated with severe hyperlactatemia in critically ill patients. We therefore aimed to evaluate the etiology of severe hyperlactatemia (defined as a lactate level >10 mmol/L) in a large cohort of unselected ICU patients. We also aimed to evaluate the association between severe hyperlactatemia and lactate clearance with ICU mortality. METHODS: In this retrospective, observational study at an University hospital department with 11 ICUs during the study period between 1 April 2011 and 28 February 2013, we screened 14,040 ICU patients for severe hyperlactatemia (lactate >10 mmol/L). RESULTS: Overall mortality in the 14,040 ICU patients was 9.8 %. Of these, 400 patients had severe hyperlactatemia and ICU mortality in this group was 78.2 %. Hyperlactatemia was associated with death in the ICU [odds ratio 1.35 (95 % CI 1.23; 1.49; p < 0.001)]. The main etiology for severe hyperlactatemia was sepsis (34.0 %), followed by cardiogenic shock (19.3 %), and cardiopulmonary resuscitation (13.8 %). Patients developing severe hyperlactatemia >24 h of ICU treatment had a significantly higher ICU mortality (89.1 %, 155 of 174 patients) than patients developing severe hyperlactatemia <= 24 h of ICU treatment (69.9 %, 158 of 226 patients; p < 0.0001). Lactate clearance after 12 h showed a receiver-operating-characteristics area under the curve (ROC-AUC) value of 0.91 to predict ICU mortality (cut-off showing highest sensitivity and specifity was a 12 h lactate clearance of 32.8 %, Youden Index 0.72). In 268 patients having a 12-h lactate clearance <32.8 % ICU mortality was 96.6 %. CONCLUSIONS: Severe hyperlactatemia (>10 mmol/L) is associated with extremely high ICU mortality especially when there is no marked lactate clearance within 12 h. In such situations, the benefit of continued ICU therapy should be evaluated. PMID- 26556618 TI - Fentanyl as pre-emptive treatment of pain associated with turning mechanically ventilated patients: a randomized controlled feasibility study. AB - PURPOSE: To compare pain incidence and changes in pain scores with fentanyl versus placebo as pre-emptive treatment during turning and 30 min post-turning in mechanically ventilated critically ill patients. METHODS: We performed a randomized, double-blind, parallel-group, placebo-controlled clinical trial in the intensive care unit of a university hospital. Seventy-five mechanically ventilated patients were randomized to an intervention group (fentanyl) or a control group (placebo). Patients in the intervention group received 1 ug/kg (medical patients) or 1.5 ug/kg (surgical patients) of fentanyl 10 min before turning. Pain indicators were assessed using the behavioral pain scale. Safety was assessed by determining the frequency and severity of pre-defined adverse events. Pain was evaluated at rest (T0), at turn start and end (T1 and T2) and at 5, 15 and 30 min post-turning (T3, T4 and T5). RESULTS: The two groups had similar baseline characteristics. The area under the curve for BPS values was significantly smaller in the fentanyl group than in the control group [median and interquartile range (IQR): 132 (108-150) vs. 147 (125-180); p = 0.016, respectively]. Nineteen non-serious adverse events were recorded in 14 patients, with no significant between-group differences (23 % fentanyl group vs. 14 % control group; p = 0.381). CONCLUSIONS: These results suggest an intravenous bolus of fentanyl of 1 ug/kg for medical patients or 1.5 ug/kg for surgical patients reduces the incidence of turning-associated pain in critically ill patients on mechanical ventilation. ClinicalTrials.gov: NCT 01950000. PMID- 26556619 TI - Effects of chest compression on secretion removal, lung mechanics, and gas exchange in mechanically ventilated patients: a crossover, randomized study. PMID- 26556620 TI - Do we need ARDS? PMID- 26556621 TI - Tasking the tailor to cut the coat: How to optimize individualized ICU-based palliative care? PMID- 26556622 TI - Prospective study of a proactive palliative care rounding intervention in a medical ICU. AB - PURPOSE: To evaluate the effects of a palliative care intervention on clinical and family outcomes, and palliative care processes. METHODS: Prospective, before and-after interventional study enrolling patients with high risk of mortality, morbidity, or unmet palliative care needs in a 24-bed academic intensive care unit (ICU). The intervention involved a palliative care clinician interacting with the ICU physicians on daily rounds for high-risk patients. RESULTS: One hundred patients were enrolled in the usual care phase, and 103 patients were enrolled during the intervention phase. The adjusted likelihood of a family meeting in ICU was 63% higher (RR 1.63, 95% CI 1.14-2.07, p = 0.01), and time to family meeting was 41% shorter (95% CI 52-28% shorter, p < 0.001). Adjusted ICU length of stay (LOS) was not significantly different between the two groups (6% shorter, 95% CI 16% shorter to 4% longer, p = 0.22). Among those who died in the hospital, ICU LOS was 19% shorter in the intervention (95% CI 33-1% shorter, p = 0.043). Adjusted hospital LOS was 26% shorter (95% CI 31-20% shorter, p < 0.001) with the intervention. Post-traumatic stress disorder (PTSD) symptoms were present in 9.1% of family respondents during the intervention versus 20.7% prior to the intervention (p = 0.09). Mortality, family depressive symptoms, family satisfaction and quality of death and dying did not significantly differ between groups. CONCLUSIONS: Proactive palliative care involvement on ICU rounds for high risk patients was associated with more and earlier ICU family meetings and shorter hospital LOS. We did not identify differences in family satisfaction, family psychological symptoms, or family-rated quality of dying, but had limited power to detect such differences. PMID- 26556623 TI - Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems. AB - Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50 degrees C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. PMID- 26556624 TI - Particle contamination of parenteralia and in-line filtration of proteinaceous drugs. AB - Protein drug products play an important role in the treatment of severe diseases. However, due to the instability of these complex molecules, protein aggregates can form which can compromise drug safety and efficacy including immunogenic reactions. In-line filtration during the administration of these drugs can serve as a final safeguarding step to protect patients from risks associated with proteinaceous particles. A unique analysis of more than 300 marketed protein drug products revealed that already around 16% of all these products are filtered during preparation or administration. Further, the research revealed that no standardized filtration practice exists. Broad variances regarding filter membrane or pore size are found and sometimes no specifications are mentioned at all. The benefits as well as possible negative impacts of filtration like filter shedding, extractables or drug adsorption are critically assessed. Several proposals to improve the current filtration practice and to expand the number of in-line filtered protein drug products are made. The suggestions include the demand for the specific usage of one filter membrane type, the establishment of a filtration routine for unfiltered protein drugs and a statistical analysis between filtered and non-filtered products with similar formulations to identify possible differences in the immunogenicity rate. PMID- 26556625 TI - Production of Korean Idiomatic Utterances Following Left- and Right-Hemisphere Damage: Acoustic Studies. AB - PURPOSE: This study investigates the effects of left- and right-hemisphere damage (LHD and RHD) on the production of idiomatic or literal expressions utilizing acoustic analyses. METHOD: Twenty-one native speakers of Korean with LHD or RHD and in a healthy control (HC) group produced 6 ditropically ambiguous (idiomatic or literal) sentences in 2 different speech tasks: elicitation and repetition. Utterances were analyzed using durational and fundamental-frequency (F0) measures. Listeners' goodness ratings (how well each utterance represented its category: idiomatic or literal) were correlated with acoustic measures. RESULTS: During the elicitation tasks, the LHD group differed significantly from the HC group in durational measures. Significant differences between the RHD and HC groups were seen in F0 measures. However, for the repetition tasks, the LHD and RHD groups produced utterances comparable to the HC group's performance. Using regression analysis, selected F0 cues were found to be significant predictors for goodness ratings by listeners. CONCLUSIONS: Using elicitation, speakers in the LHD group were deficient in producing durational cues, whereas RHD negatively affected the production of F0 cues. Performance differed for elicitation and repetition, indicating a task effect. Listeners' goodness ratings were highly correlated with the production of certain acoustic cues. Both the acoustic and functional hypotheses of hemispheric specialization were supported for idiom production. PMID- 26556626 TI - Peptidomimetic suppresses proliferation and invasion of gastric cancer cells by fibroblast growth factor 2 signaling cascade blockage. AB - Fibroblast growth factor 2 (FGF2) is closely involved in a variety of tumors, including gastric cancer (GC). FGF2 inhibitors exert good antitumor activity, but no FGF2 inhibitor has been employed for clinical use. To obtain a low-toxicity, stable peptidomimetic (called P29) target to FGF2, the affinity between P29 and FGF2 was detected by surface plasmon resonance. The stability of P29 was measured by high performance liquid chromatography. MTT assay and transwell assay were used to access the proliferative and invasive ability of GC cells, respectively. Western blot assay and flow cytometric analysis were applied to study the mechanism of P29. P29 possessed high affinity with FGF2 and a longer half-life in vitro. P29 suppressed the FGF2-induced proliferation of GC cells. It also inhibited the phosphorylation of FRS2, ERK1/2, and AKT triggered by FGF2 in GC. In addition, P29 blocked GC cell transformation from the G1/G0 phase to the S phase and weakened the invasive capability of GC cells. In this paper, we present a novel FGF2 inhibitor that could exert improved anticancer effect in GC in vitro. PMID- 26556627 TI - Gemcitabine upregulates ABCG2/BCRP and modulates the intracellular pharmacokinetic profiles of bioluminescence in pancreatic cancer cells. AB - A lack of methods capable of exploring real-time intracellular drug deposition has since limited the investigation of gemcitabine-induced multidrug resistance in vitro and in vivo. Specifically, resistance induced by D-luciferin, a substrate of the breast cancer resistance protein (ABCG2/BCRP), has recently attracted clinical attention, but further investigation has been limited. Herein, the intracellular pharmacokinetic behavior of D-luciferin was investigated in pancreatic cancer cell lines in real time by using bioluminescence imaging. To achieve this feat, BxPC3 and Panc1 pancreatic cancer cells overexpressing firefly luciferase were treated with gemcitabine in a dose and time gradient manner in vitro. The intracellular pharmacokinetic profiles of each group were then determined through the acquisition of bioluminescent signal intensity of D luciferin in cells. Simultaneously, key pharmacokinetic parameters including area under the curve, elimination rate constant (K), and mean resident time were calculated according to the noncompartment model. ABCG2 protein levels following gemcitabine treatment were detected through western blot, and gemcitabine showed no significant effect on luciferase activity over dimethyl sulfoxide (DMSO) as a control (P>0.05). However, gemcitabine significantly increased K values while suppressing area under the curve and mean resident time compared with DMSO (P<0.05) and increased ABCG2 expression over DMSO-treated cells. In addition, gemcitabine increased the elimination rate of the ABCG2 substrate, D-luciferin, and decreased D-luciferin accumulation in BxPC3 and Panc1 cells in a dose response manner. Advances made herein illustrate the versatility of the in-vitro bioluminescent model and its capability to observe the onset of chemoresistance in real time. PMID- 26556628 TI - CRISPR/Cas9-mediated viral interference in plants. AB - BACKGROUND: The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. RESULTS: In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. CONCLUSIONS: These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections. PMID- 26556629 TI - Flotillin-2 Gene Is Associated with Coronary Artery Disease in Chinese Han Population. AB - BACKGROUND: Flotillin-2, an important protein of vesicular endocytosis, is commonly used as a marker protein for lipid microdomains. It plays an essential role in cellular cholesterol uptake and biliary cholesterol reabsorption. Excessive cholesterol intake could cause dyslipidemia, which is a major risk factor of coronary artery disease (CAD). AIMS: To investigate the association between the human flotillin-2 gene polymorphism and CAD in the Chinese Han population. MATERIALS AND METHODS: Three single-nucleotide polymorphisms (SNPs; rs10205, rs3816848 and rs8081659) of the flotillin-2 gene were genotyped by real time polymerase chain reaction in 307 CAD patients and 441 control subjects. RESULTS: The genotypic distribution of these three SNPs was significantly different between CAD patients and control subjects (all p < 0.05). There were significant differences in the plasma levels of total cholesterol (TC) among different genotypes in the CAD group and control group. For rs3816848, CAD patients with the GG genotype had a higher level of TC than those with an AG or AA genotype (p < 0.001). For rs8081659, CAD patients with TT genotype had a higher level of TC than those with a CT or CC genotype (p < 0.001). Multiple logistic regression analysis showed that the GG genotype of rs3816848 was an independent risk factor for CAD (odds ratio [OR] = 1.786; 95% CI = 1.099-2.902; p = 0.019). CONCLUSION: There was a strong association between polymorphisms of flotillin-2 gene and CAD in the Chinese Han population. Persons with the GG genotype of rs3816848 may have a higher risk of CAD. Moreover, the plasma levels of TC were significantly different among the different genotypes of the rs3816848 and rs8081659 SNPs in the CAD group as well as the control group. PMID- 26556631 TI - Structural variations and molten globule state in Arisaema helliborifolium lectin under various treatments as monitored by spectroscopy. AB - Solvent perturbation was used to study variations in structure of Arisaema helliborifolium lectin (AHL) with the help of circular dichroism (CD), intrinsic fluorescence (IF), extrinsic fluorescence, quenching and dynamic light scattering (DLS). AHL was studied under acidic, alkaline and 6 M guanidine hydrochloride (GuHCl) equilibrium states. Three structural states were identified for AHL at different conditions, that are native (N; pH 7.0), molten globule (MG; pH 2.0) and unfolded (U; pH 12.0). CD analysis revealed that 50% of secondary structure of AHL was beta-sheet component. A complete loss of secondary structure was observed at GuHCl treatment. The tertiary structural changes as studied by changes in microenvironment of trp residues also suggested a pH induced MG state as in case of CD. Parameter-A analysis pointed at the multi-step unfolding process of lectin under varying pH (pH 1-13). A comparision of CD and IF data further indicated that different pathways were followed for secondary and tertiary structure unfolding. Tryptophans of native AHL were only partially exposed to solvent belonging to Class II. Hydrodynamic diameter (Dh ) measurements of AHL via DLS also confirmed of a pH induced molten globule. A thermally induced molten globule was identified for AHL between 54-60 degrees C as monitored by DLS. An irreversible thermal denaturation was observed with the formation of a large aggregate. The Dh of AHL at neutral pH was confirmed by transmission electron microscopy (TEM). PMID- 26556630 TI - PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila. AB - The recruitment of GDP/GTP exchange factors (GEFs) to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH) domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos. PMID- 26556632 TI - Correction: Risk of Bias in Reports of In Vivo Research: A Focus for Improvement. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002273.]. PMID- 26556633 TI - The effect of dietary water soluble carbohydrate to nitrogen ratio on nitrogen partitioning and isotopic fractionation of lactating goats offered a high nitrogen diet. AB - The objective of this study was to investigate the relationship between nitrogen (N) partitioning and isotopic fractionation in lactating goats consuming diets with a constant high concentration of N and increasing levels of water soluble carbohydrate (WSC). Eight lactating goats were offered four different ratios of WSC : N in the diet. A two-period incomplete cross-over design was used, with two goats assigned to each treatment in each period. N balance measurements were conducted, with measurement of feed N intake and total output of N in milk, faeces and urine. Treatment, period and infusion effects were tested using general ANOVA; the relationships between variables were analysed by linear regression. Dietary treatment and period had significant effects on dry matter (DM) intake (g/day). DM digestibility (g/kg DM) and N digestibility (g/kg N) increased as the ratio of WSC : N increased in the diet. No treatment effect was observed on milk urea N concentration (g/l) or urinary excretion of purine derivatives (mM/day). Although dietary treatment and period had significant effects on N intake, the change of N intake was small; no effect was observed for N partitioning among faeces, milk and urine. Milk, plasma and faeces were enriched in 15N compared with feed, whilst urine was depleted in 15N relative to feed. No significant relationship was established between N partitioning and isotopic fractionation. This study failed to confirm the potential to use N isotopic fractionation as an indicator of N partitioning in dairy goats when diets provided N in excess to requirements, most likely because the range of milk N output/N intake and urinary N output/N intake were narrow. PMID- 26556634 TI - Subtle Structural Aspects of Propylene-Based Copolymers as Revealed by Raman Spectroscopy. AB - Raman spectroscopy is used to elucidate fine details of the rather complex microstructure of ethylene-propylene copolymers (EPCs). This paper is focused on a series of commercial EPCs (Versify by Dow) with well-characterized ethylene content. Particular emphasis is given on the analysis of crystal type and content and their relation with EPC chain microstructure. Information provided by Raman is compared with that obtained by differential scanning calorimetry (DSC), a well established technique widely used in the polymer field. Temperature-resolved Raman experiments are also carried out to interpret more precisely the complex melting patterns observed in the DSC traces. These experiments reveal with more detail the crystal chemical composition and melting temperature ranges of EPC samples, key features to design processing conditions that guarantee optimum lifetime and recyclability of overmolded parts. PMID- 26556635 TI - Association of Frailty and Cardiometabolic Risk Among Community-Dwelling Middle Aged and Older People: Results from the I-Lan Longitudinal Aging Study. AB - The aim of this study was to evaluate the association of cardiometabolic risk and frailty through a community-based aging cohort in Taiwan In total, 1839 participants (men, 47.5%; mean age 63.9 +/- 9.3 years) from the first wave of the I-Lan longitudinal cohort study, recruited between August of 2011 and August of 2013, were retrieved for the analysis of this cross-sectional study. Frailty was defined by Cardiovascular Health Study (CHS) criteria, encompassing un intentional weight loss, slow walk speed, poor grip strength, exhaustion, and low activity. Comparisons between cardiometabolic risk and frailty status were performed after adjustment for age, hormone parameters, functional measurements, and skeletal muscle mass. Independent association of cardiometabolic risk and frailty status was identified through the multivariate logistic regression model. We found that the prevalence of frailty and pre-frial were 6.8% and 40.5%, respectively. Adjustments for age, blood pressure, low-density lipoprotein cholesterol (LDL-C), uric acid, creatinine, and carotid intima media thickness were not significantly associated with frailty. However, lower total cholesterol and high-density lipoprotein cholesterol (HDL-C), higher high-sensitivity C reactive protein (hsCRP) and glycemia profiles were significantly associated with frailty. For hormone parameters, dehydroepiandrosterone sulfate (DHEA-S), insulin like growth factor-1 (IGF-1), and free androgen index were not significantly associated with frailty after age adjustment. In a multivariate logistic regression model, abdominal obesity, homeostasis model assessment of insulin resistance (HOMA-IR), and hsCRP were significantly associated with frailty. The odds ratio (OR) for frailty was 3.57 (95% confidence interval [CI] 1.88-6.78, p < 0.001), 1.30 (95% CI 1.02-1.66, p = 0.032), and 1.66 (95% CI 1.10-2.49, p = 0.016), respectively, in a fully adjusted model. Conversely, higher total cholesterol was associated with a lower prevalence of frailty (OR = 0.44, 95% CI 0.22-0.89, p = 0.023) in the final model. In this study, abdominal obesity, insulin resistance, and inflammation were significantly associated with frailty, and the effect was independent of functional measurement and decline of skeletal muscle mass. An integrated approach targeted at cardiometabolic aging and frailty is needed in clinical practice. PMID- 26556637 TI - Description of 'Candidatus Berkiella aquae' and 'Candidatus Berkiella cookevillensis', two intranuclear bacteria of freshwater amoebae. AB - Two novel bacteria of the phylum Proteobacteria were isolated during searches for amoeba-resistant micro-organisms in natural and constructed water systems. Strain HT99 was isolated from amoebae found in the biofilm of an outdoor hot tub in Cookeville, Tennessee, USA, and strain CC99 was isolated from amoebae in the biofilm of a cooling tower in the same city. Both bacteria were Gram-stain negative cocci to coccobacilli, unculturable on conventional laboratory media, and were found to be intranuclear when maintained in Acanthamoeba polyphaga. The genomes of both isolates were completely sequenced. The genome of CC99 was found to be 3.0 Mbp with a 37.9 mol% DNA G+C content, while the genome of HT99 was 3.6 Mbp with a 39.5 mol% DNA G+C content. The 16S rRNA gene sequences of the two isolates were 94 % similar to each other. Phylogenetic comparisons of the 16S rRNA, mip and rpoB genes, the DNA G+C content and the fatty acid composition demonstrated that both bacteria are members of the order Legionellales, and are most closely related to Coxiella burnetii. The phenotypic and genetic evidence supports the proposal of novel taxa to accommodate these strains; however, because strains HT99 and CC99 cannot be cultured outside of the amoeba host, the respective names 'Candidatus Berkiella aquae' and 'Candidatus Berkiella cookevillensis' are proposed. PMID- 26556636 TI - Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury. AB - BACKGROUND: Our aim is to investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. METHODS: We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. RESULTS: Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol (EtOH) compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and up regulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute EtOH administration. The absence of microbiota was also associated with increased hepatic expression of EtOH metabolizing enzymes, which led to faster EtOH elimination from the blood and lower plasma EtOH concentrations. Intestinal levels of EtOH-metabolizing genes showed regional expression differences and were overall higher in germ-free mice relative to conventional mice. CONCLUSIONS: Our findings indicate that absence of the intestinal microbiota increases hepatic EtOH metabolism and the susceptibility to binge-like alcohol drinking. PMID- 26556639 TI - Early symptom change in adult outpatients: Relationship with patient characteristics and therapeutic alliance. AB - OBJECTIVE: This study has three aims: (1) to identify early change trajectories, (2) to examine patient characteristics predicting trajectory classes, and (3) to investigate the moderating effect of trajectory class membership on the working alliance. METHOD: In a sample of 402 outpatients (M age = 38.27, 64.9% women), outcome scores (OQ-45) on three time points (sessions 1, 3, and 5) were analysed by means of Latent Class Growth Curve Analysis. A multinomial logistic regression was used to investigate whether patient's age, gender, initial distress (OQ-45), and personality traits (Dimensional Assessment of Personality Pathology-Short Form) predicted trajectory class membership. A repeated-measures ANOVA examined whether differences in trajectory classes moderated the alliance quality (Working Alliance Inventory-Short version) over time. RESULTS: Four trajectory classes were identified: High distress-no change; moderate/high distress-small improvement, low distress-moderate improvement, and moderate/low distress-strong improvement. Gender, initial distress, and emotion dysregulation significantly predicted patients' trajectory class membership. The Task/Goal alliance component increased linearly over time, whereas the Bond component followed a reversed U shaped pattern. The alliance was not moderated by trajectory class membership. CONCLUSIONS: Four clinically relevant subgroups could be identified on the basis of the early symptom change trajectories. Gender, initial psychological distress, and emotion dysregulation predicted patient's trajectory class membership. Trajectory class membership did not influence the development of the early working alliance. PRACTITIONER POINTS: As early change in highly distressed patients (Axis I and II) is not characterized by significant symptom change, clinicians should support and facilitate emotion regulation and social skills. Investing in a strong alliance is recommended, although it does not differentiate early responders from non-responders. PMID- 26556638 TI - In Vivo and protease-activated receptor-1-mediated platelet activation in patients presenting for cardiac catheterization. AB - Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether in vivo and thrombin receptor activating peptide (TRAP)-stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. In vivo and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. In vivo platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all p<=0.02). Patients with an acute coronary syndrome (ACS; n=125) had significantly higher levels of in vivo MPA than patients without ACS (n=437; p=0.01). In the overall study population (n=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA in vivo and in response to TRAP were similar in patients without and with subsequent ischemic events (all p>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n=459), stent implantation (n=205) or ACS (n=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, in vivo and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization. PMID- 26556640 TI - How health services can improve access to abortion. PMID- 26556641 TI - [3]Ferrocenophanes with the bisphosphanotetryl bridge: inorganic rings on the way to tetrylenes. AB - A series of [3]ferrocenophanes with functional P-E-P motifs (E = group 14 fragments) is reported. Out of these, the silicon compounds with the general formula Fe(C5H4PtBu)2SiXY (XY = Cl2, Br2, I2, H2, HCl) have been characterized by spectroscopic means and the bonding situation was analyzed using X-ray crystallography and quantum chemical calculations. Despite the two stereogenic phosphanyl centers, most of the [3]ferrocenophanes have been obtained as single isomers in the course of stereospecific reactions. The corresponding stannylene Fe(C5H4PtBu)2Sn has been obtained in the form of its dimeric adduct. PMID- 26556642 TI - A Simple Device to Rapidly Prepare Whole Mounts of the Mouse Intestine. AB - Preparing whole mounts of the mouse small intestine and colon for subsequent analysis or quantification can be time consuming and difficult. We describe the use of a simple device to cut and 'roll' mouse intestines to rapidly prepare whole mount preparations of superior and uniform quality to that which can be achieved by hand. The device comprises a base that holds 4 stainless steel rods and a top, which acts a cutting guide. The rods are inserted into the lumen of the small intestine [divided into thirds] and the colon. The rods and samples are then placed over a piece of filter paper or card into the holding slots in the base of the device. The top of the device is then positioned and serves as a cutting guide. The two angled sections in the center of the top piece are used to guide a knife or scalpel and cut the intestines longitudinally on the top of the rods. Once the intestinal sections have been cut, the top is removed and the card, tissue and rods gently removed from the device and placed on the bench. The rods are then gently rolled sideways to flatten and stick the intestinal segments onto the underlying piece of filter paper or card. The final preparation can then be examined or fixed and stored for later analysis. The preparations are invaluable for the study of intestinal changes in normal or genetically modified mouse models. The preparations have been used for the study and quantification of the effects of inflammation (colitis), damage, pre-cancerous lesions (aberrant crypt foci (ACFs) and mucin depleted foci (MDFs)) and polyps or tumors. PMID- 26556643 TI - Affordable, web-based surgical skill training and evaluation tool. AB - Advances in the medical field have increased the need to incorporate modern techniques into surgical resident training and surgical skills learning. To facilitate this integration, one approach that has gained credibility is the incorporation of simulator based training to supplement traditional training programs. However, existing implementations of these training methods still require the constant presence of a competent surgeon to assess the surgical dexterity of the trainee, which limits the evaluation methods and relies on subjective evaluation. This research proposes an efficient, effective, and economic video-based skill assessment technique for minimally invasive surgery (MIS). It analyzes a surgeon's hand and surgical tool movements and detects features like smoothness, efficiency, and preciseness. The system is capable of providing both real time on-screen feedback and a performance score at the end of the surgery. Finally, we present a web-based tool where surgeons can securely upload MIS training videos and receive evaluation scores and an analysis of trainees' performance trends over time. PMID- 26556644 TI - Gene and sample selection using T-score with sample selection. AB - Gene selection from high-dimensional microarray gene-expression data is statistically a challenging problem. Filter approaches to gene selection have been popular because of their simplicity, efficiency, and accuracy. Due to small sample size, all samples are generally used to compute relevant ranking statistics and selection of samples in filter-based gene selection methods has not been addressed. In this paper, we extend previously-proposed simultaneous sample and gene selection approach. In a backward elimination method, a modified logistic regression loss function is used to select relevant samples at each iteration, and these samples are used to compute the T-score to rank genes. This method provides a compromise solution between T-score and other support vector machine (SVM) based algorithms. The performance is demonstrated on both simulated and real datasets with criteria such as classification performance, stability and redundancy. Results indicate that computational complexity and stability of the method are improved compared to SVM based methods without compromising the classification performance. PMID- 26556645 TI - Resource efficient data compression algorithms for demanding, WSN based biomedical applications. AB - During the last few years, medical research areas of critical importance such as Epilepsy monitoring and study, increasingly utilize wireless sensor network technologies in order to achieve better understanding and significant breakthroughs. However, the limited memory and communication bandwidth offered by WSN platforms comprise a significant shortcoming to such demanding application scenarios. Although, data compression can mitigate such deficiencies there is a lack of objective and comprehensive evaluation of relative approaches and even more on specialized approaches targeting specific demanding applications. The research work presented in this paper focuses on implementing and offering an in depth experimental study regarding prominent, already existing as well as novel proposed compression algorithms. All algorithms have been implemented in a common Matlab framework. A major contribution of this paper, that differentiates it from similar research efforts, is the employment of real world Electroencephalography (EEG) and Electrocardiography (ECG) datasets comprising the two most demanding Epilepsy modalities. Emphasis is put on WSN applications, thus the respective metrics focus on compression rate and execution latency for the selected datasets. The evaluation results reveal significant performance and behavioral characteristics of the algorithms related to their complexity and the relative negative effect on compression latency as opposed to the increased compression rate. It is noted that the proposed schemes managed to offer considerable advantage especially aiming to achieve the optimum tradeoff between compression rate-latency. Specifically, proposed algorithm managed to combine highly completive level of compression while ensuring minimum latency thus exhibiting real-time capabilities. Additionally, one of the proposed schemes is compared against state-of-the-art general-purpose compression algorithms also exhibiting considerable advantages as far as the compression rate is concerned. PMID- 26556646 TI - Crowdsourcing Twitter annotations to identify first-hand experiences of prescription drug use. AB - Self-reported patient data has been shown to be a valuable knowledge source for post-market pharmacovigilance. In this paper we propose using the popular micro blogging service Twitter to gather evidence about adverse drug reactions (ADRs) after firstly having identified micro-blog messages (also know as "tweets") that report first-hand experience. In order to achieve this goal we explore machine learning with data crowdsourced from laymen annotators. With the help of lay annotators recruited from CrowdFlower we manually annotated 1548 tweets containing keywords related to two kinds of drugs: SSRIs (eg. Paroxetine), and cognitive enhancers (eg. Ritalin). Our results show that inter-annotator agreement (Fleiss' kappa) for crowdsourcing ranks in moderate agreement with a pair of experienced annotators (Spearman's Rho=0.471). We utilized the gold standard annotations from CrowdFlower for automatically training a range of supervised machine learning models to recognize first-hand experience. F-Score values are reported for 6 of these techniques with the Bayesian Generalized Linear Model being the best (F-Score=0.64 and Informedness=0.43) when combined with a selected set of features obtained by using information gain criteria. PMID- 26556647 TI - Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU). AB - Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90 degrees for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging. PMID- 26556648 TI - Assessment of Arabic phonological awareness and its relation to word reading ability. AB - Phonological awareness (PA) is one of the most important components in the development of normal reading ability. It refers to the ability to detect and manipulate the sound structure of words independently of their meaning. The current study aimed to assess Arabic PA skills and the relation to word reading abilities in Egyptian Arabic-speaking children. The designed assessment was applied to 80 typically developing children, divided into two subgroups ranging in age from 5 years 6 months to 8 years 6 months. The design of assessment involved six PA tasks covering three levels: rhyme awareness, syllabic awareness, and phonemic awareness, as well as the assessment of reading abilities that include real word and nonsense word reading tasks. Descriptive statistics (mean, standard deviation), Student's t tests, and Pearson correlation coefficient tests were used to analyze the data. The reliability of the test was proven using the test-retest procedure. Validity of the test was estimated through internal consistency validity. The results revealed that the Arabic PA assessment test (APAAT) proved to be a reliable and valid tool for assessing Arabic reading skills. Findings from the study provided important insights into the developmental patterns of Arabic PA. In addition, the findings revealed a strong relationship between phonological awareness skills and the proficiency in word reading abilities in Arabic school-aged children. PMID- 26556649 TI - Characterization of the Chloride Channel-Like, AtCLCg, Involved in Chloride Tolerance in Arabidopsis thaliana. AB - In plant cells, anion channels and transporters are essential for key functions such as nutrition, ion homeostasis and resistance to biotic or abiotic stresses. We characterized AtCLCg, a member of the chloride channel (CLC) family in Arabidopsis localized in the vacuolar membrane. When grown on NaCl or KCl, atclcg knock-out mutants showed a decrease in biomass. In the presence of NaCl, these mutants overaccumulate chloride in shoots. No difference in growth was detected in response to osmotic stress by mannitol. These results suggest a physiological function of AtCLCg in the chloride homeostasis during NaCl stress. AtCLCg shares a high degree of identity (62%) with AtCLCc, another vacuolar CLC essential for NaCl tolerance. However, the atclcc atclccg double mutant is not more sensitive to NaCl than single mutants. As the effects of both mutations are not additive, gene expression analyses were performed and revealed that: (i)AtCLCg is expressed in mesophyll cells, hydathodes and phloem while AtCLCc is expressed in stomata; and (ii)AtCLCg is repressed in the atclcc mutant background, and vice versa. Altogether these results demonstrate that both AtCLCc and AtCLCg are important for tolerance to excess chloride but not redundant, and form part of a regulatory network controlling chloride sensitivity. PMID- 26556650 TI - TBL3 and TBL31, Two Arabidopsis DUF231 Domain Proteins, are Required for 3-O Monoacetylation of Xylan. AB - Xylan, a major constituent of secondary cell walls, is made of a linear chain of beta-1,4-linked xylosyl residues that are often substituted with glucuronic acid/methylglucuronic acid side chains and acetylated at O-2 and O-3. Previous studies have shown that ESK1, an Arabidopsis DUF231 protein, is an acetyltransferase catalyzing 2-O- and 3-O-monoacetylation of xylan. However, the esk1 mutation only causes a partial loss of xylan 2-O- and 3-O-monoacetylation, suggesting that additional xylan acetyltransferase activities are involved. In this report, we demonstrated the essential roles of two other Arabidopsis DUF231 genes, TBL3 and TBL31, in xylan acetylation. The expression of both TBL3 and TBL31 was shown to be induced by overexpression of the secondary wall master transcriptional regulator SND1 (secondary wall-associated NAC domain protein1) and down-regulated by simultaneous mutations of SND1 and its paralog NST1, indicating their involvement in secondary wall biosynthesis. beta-Glucurondase (GUS) reporter gene analysis showed that TBL3 and TBL31 were specifically expressed in the xylem and interfascicular fibers in stems and the secondary xylem in root hypocotyls. Expression of fluorescent protein-tagged TBL3 and TBL31 in protoplasts revealed their localization in the Golgi, where xylan biosynthesis occurs. Although mutation of either TBL3 or TBL31 alone did not cause any apparent alterations in cell wall composition, their simultaneous mutations were found to result in a reduction in xylan acetylation. Further structural analysis demonstrated that the tbl3 tbl31 double mutant had a specific reduction in 3-O acetylation of xylan. In addition, the tbl3 tbl31 esk1 triple mutant displayed a much more drastic decrease in 3-O-acetylation of xylan, indicating their functional redundancy in xylan 3-O-acetylation. These findings indicate that TBL3 and TBL31 are secondary wall-associated DUF231 genes specifically involved in xylan 3-O-acetylation. PMID- 26556651 TI - Finding the Subcellular Location of Barley, Wheat, Rice and Maize Proteins: The Compendium of Crop Proteins with Annotated Locations (cropPAL). AB - Barley, wheat, rice and maize provide the bulk of human nutrition and have extensive industrial use as agricultural products. The genomes of these crops each contains >40,000 genes encoding proteins; however, the major genome databases for these species lack annotation information of protein subcellular location for >80% of these gene products. We address this gap, by constructing the compendium of crop protein subcellular locations called crop Proteins with Annotated Locations (cropPAL). Subcellular location is most commonly determined by fluorescent protein tagging of live cells or mass spectrometry detection in subcellular purifications, but can also be predicted from amino acid sequence or protein expression patterns. The cropPAL database collates 556 published studies, from >300 research institutes in >30 countries that have been previously published, as well as compiling eight pre-computed subcellular predictions for all Hordeum vulgare, Triticum aestivum, Oryza sativa and Zea mays protein sequences. The data collection including metadata for proteins and published studies can be accessed through a search portal http://crop-PAL.org. The subcellular localization information housed in cropPAL helps to depict plant cells as compartmentalized protein networks that can be investigated for improving crop yield and quality, and developing new biotechnological solutions to agricultural challenges. PMID- 26556652 TI - Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes. AB - AIM: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals. RESULTS: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. CONCLUSION: Treatment naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA. PMID- 26556654 TI - Non-templated ambient nanoperforation of graphene: a novel scalable process and its exploitation for energy and environmental applications. AB - Nano-perforation of 2D graphene sheets is a recent and strategically significant means to exploit such materials in modern applications such as energy production and storage. However, current options for the synthesis of holey graphene (hG) through nano-perforation of graphene involve industrially undesirable steps viz., usage of expensive/noble metal or silica nanoparticle templates and/or hazardous chemicals. This severely hampers its scope for large scale production and further exploitation. Herein, we report for the first time a scalable non-templated route to produce hG at ambient conditions. Nano-perforation is achieved with tunable pore size via the simple few layer co-assembly of silicate-surfactant admicelles along the surface of graphene oxide. A gentle alkali treatment and a reduction at optimized conditions readily yielded holey graphene with a remarkable capacitance (~250 F g(-1)) and interesting adsorption abilities for pollutants. Density functional theory based computational studies reveal interesting insights on the template free nano-perforation at a molecular level. This simple rapid process not only excludes the need for expensive templates and harmful chemicals to yield hG at attractively ambient, chemically placid and industrially safer conditions, but also creates no hurdles in terms of scaling up. PMID- 26556653 TI - Lack of Sex Difference in Minimum Local Analgesic Concentration of Ropivacaine for Ultrasound-Guided Supraclavicular Brachial Plexus Block. AB - BACKGROUND: Sex differences, which may be an important variable for determining anesthetic requirements, have not been well investigated in the aspect of local anesthetic. This investigation aimed to compare the minimum local analgesic concentration (MLAC) of ropivacaine for ultrasound-guided supraclavicular brachial plexus block (US-SCB) between men and women. MATERIAL AND METHODS: Patients aged 18-45 years undergoing elective forearm, wrist, or hand surgeries under US-SCB were divided into 2 groups according to sex. The initial concentration was 0.375% ropivacaine 20 mL and the concentration for the next patient was determined by the up-down technique at 0.025% intervals. Success was defined as the absence of any pain in response to a pinprick in the region of all 4 terminal nerves and the skin incision within 45 min. The primary outcome was the MLAC of ropivacaine, which was estimated by the Dixon and Massey method. The analgesia duration, which was defined as the time from the end of the US-SCB injection to the time of feeling discomfort and need for additional analgesics, was observed for each patient. RESULTS: The MLAC of ropivacaine 20 mL for US-SCB was 0.2675% (95% confidence interval [CI], 0.2512-0.2838%) in men and 0.2675% (95% CI, 0.2524-0.2826%) in women. There was no significant difference in MLAC or the analgesia duration between the 2 groups (P>0.05). CONCLUSIONS: We found no significant sex-related differences in MLAC or analgesia duration of ropivacaine for US-SCB. PMID- 26556655 TI - Evaluation of the in vivo thrombolytic activity of a metalloprotease from Bothrops atrox venom using a model of venous thrombosis. AB - BACKGROUND: Due to the importance of blood coagulation and platelet aggregation in brain- and cardiovascular diseases, snake venom proteins that interfere in these processes have received significant attention in recent years considering their potential to be used as models for new drugs. OBJECTIVES: This study aimed at the evaluation of the in vivo thrombolytic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom. METHODS: In vivo thrombolytic activity of Batroxase was tested on a model of venous thrombosis in rats, with partial stenosis of the inferior vena cava, and vessel wall injury with ferric chloride at 10% for 5 min. After formation of the thrombus, increasing amounts of Batroxase were administered intravenously. The prescription medication Alteplase (tissue-type plasminogen activator) was used as positive control for thrombolytic activity, while saline was used as negative control. Bleeding time was assessed with a tail bleeding assay. RESULTS: Batroxase presented thrombolytic activity in vivo in a concentration-dependent manner, with 12 mg/kg of the metalloprotease causing a thrombus reduction of 80%, a thrombolytic activity very similar to the one observed for the positive control Alteplase (85%). The tail bleeding time was not altered by the administration of Batroxase, while it increased 3.5 times with Alteplase. Batroxase presented fibrinolytic and fibrinogenolytic activities in vitro, which were inhibited by alpha 2-macroglobulin. CONCLUSION: Batroxase presents thrombolytic activity in vivo, thus demonstrating a possible therapeutic potential. The inactivation of the metalloprotease by alpha 2-macroglobulin may reduce its activity, but also its potential side effects, as seen for bleeding time. PMID- 26556656 TI - A simple non-invasive technique for venom milking from a solitary wasp Delta conoideum Gmelin (Hymenoptera: Vespidae). AB - Prospecting wasp, ant and bee venom for active bio-molecules has gained considerable interest among researchers in recent years. Collecting sufficient quantity of venom from solitary wasps without sacrificing them is often difficult. Here we describe a non-invasive technique for collecting venom from a solitary wasp Delta conoideum Gmelin (Red-backed potter wasp). Venom was milked by presenting an agar block to a single female wasp for stinging. The venom was extracted from the agar block using ACN: water solvent system. The total protein in venom was estimated quantitatively and the presence of peptides in the venom was confirmed by MALDI-TOF analysis. The proposed technique is non-invasive and pure venom can be repeatedly 'milked' using this method from other wasps and also bees without the need for sacrificing a large number of individuals. PMID- 26556657 TI - Impact of Staffing on Access to Palliative Care in U.S. Hospitals. AB - BACKGROUND: Over the past decade over two-thirds of U.S. hospitals have established palliative care programs. National data on palliative care program staffing and its association with operational outcomes are limited. OBJECTIVE: The objective of this report is to examine the impact of palliative care program staffing on access to palliative care in U.S. hospitals. METHODS: Data from the National Palliative Care RegistryTM for 2014 were used to calculate staffing levels, palliative care service penetration, and time to initial palliative care consultation for 398 palliative care programs operating across 482 U.S. hospitals. RESULTS: Hospital-based palliative care programs reported an average service penetration of 4.4%. Higher staffing levels were associated with higher service penetration; higher service penetration was associated with shorter time to initial palliative care consultation. DISCUSSION: This report demonstrates that operational effectiveness, as measured by staffing and palliative care service penetration, is associated with shorter time to palliative care consultation. PMID- 26556658 TI - Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders. AB - Recent neuroscience research has established the adult brain as a dynamic organ having a unique ability to undergo changes with time. Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain. Activation of these glial cells is a major component of the neuroinflammatory responses underlying brain injury and neurodegeneration. Glial cells execute functional reaction programs in response to diverse microenvironmental signals manifested by neuropathological conditions. Activated microglia exist along a continuum of two functional states of polarization namely M1-type (classical/proinflammatory activation) and M2-type (alternative/anti-inflammatory activation) as in macrophages. The balance between classically and alternatively activated microglial phenotypes influences disease progression in the CNS. The classically activated state of microglia drives the neuroinflammatory response and mediates the detrimental effects on neurons, whereas in their alternative activation state, which is apparently a beneficial activation state, the microglia play a crucial role in tissue maintenance and repair. Likewise, in response to immune or inflammatory microenvironments astrocytes also adopt neurotoxic or neuroprotective phenotypes. Reactive astrocytes exhibit two distinctive functional phenotypes defined by pro- or anti-inflammatory gene expression profile. In this review, we have thoroughly covered recent advances in the understanding of the functional polarization of brain and peripheral glia and its implications in neuroinflammation and neurological disorders. The identifiable phenotypes adopted by neuroglia in response to specific insult or injury can be exploited as promising diagnostic markers of neuroinflammatory diseases. Furthermore, harnessing the beneficial effects of the polarized glia could undoubtedly pave the way for the formulation of novel glia-based therapeutic strategies for diverse neurological disorders. PMID- 26556659 TI - Spinocerebellar degeneration: Discrepancies between clinical and pathological diagnoses. AB - To improve the diagnostic accuracy of sporadic spinocerebellar degeneration (SCD), we assessed the clinical and pathological data of 1494 consecutive autopsy cases. The number of patients who received a diagnosis of sporadic SCD (including multiple system atrophy) either clinically or pathologically was 19 (1.3%). We identified six cases with clinical misdiagnoses of SCD that were confirmed pathologically as progressive supranuclear palsy (PSP, four cases), basilar artery thrombosis (one case) and unclassified tauopathy (one case). The total number of patients who received a clinical diagnosis of sporadic SCD was 93 and the positive predictive value was 93.5%. We also identified 13 autopsy cases that were pathologically confirmed as SCD, but had been clinically misdiagnosed as having other disorders. Their clinical diagnoses comprised progressive supranuclear palsy (five cases) and Parkinson's disease (PD, four cases), as well as parkinsonism with dementia, amyotrophic lateral sclerosis, paraneoplastic syndrome and multiple cerebral infarction (one case each). The results indicate that it is often difficult to distinguish PSP and PD from SCD, because of the atypical combination of symptoms or atypical timing of the appearance of symptoms, such as severe autonomic failure, cognitive impairment, poor L-dopa responsiveness, early cerebellar signs and obvious vertical gaze palsy. PMID- 26556660 TI - [Social media monitoring of asthmatic children treated in a specialized program: Parents and caregivers expectations]. AB - BACKGROUND: Social media has been used in support of patients with asthma. However, it remains unclear what are the expectations of parents or caregivers of asthmatic patients. OBJECTIVE: To evaluate the expectations of parents or caregivers of asthmatic children treated at Children's Asthma Prevention Program (PIPA), Uruguaiana, RS, in relation to the use of social media. MATERIAL AND METHOD: An observational, descriptive, cross-sectional survey of parents or caregivers of children seen at Children's Asthma Prevention Program through responses to a written questionnaire on the use of new technologies and different applications to enhance information about asthma. RESULTS: 210 parents or caregivers (median age: 25 years; age range: 18-42 years of patients were enrolled. The mean age of their children was 7.3 years (age range: 2 to 18 years), the mean duration of asthma was 4.7 years and 65% of parents/caregivers of these children had less than eight years of schooling. Most of them (72%) had no access to the Internet via cell/mobile phones and only 18% actively used to gathered information about asthma by internet. There was high interest (87%) in receiving information via social media. CONCLUSION: Parents or caregivers of children attending the PIPA program expressed high interest in using social media. However, few use it to control their children's disease. While providing a great benefit to use social media as a mean of communication in health, the content needs to be monitored for reliability and quality. The privacy of users (doctors and patients) must be preserved and it is very important to facilitate the access to Internet. PMID- 26556661 TI - [Systemic lupus erythematous and CD24v]. AB - BACKGROUND: Systemic lupus erythematous is an autoimmune disease of multifactorial etiology with genetic predisposition. Its pathogenesis involved more than 100 genes. CD24 gene can mediate various functions such as their costimulatory activity in the clonal expansion of T cells. The single nucleotide polymorphism, resulting in a non-conservative replacement of alanine to valine (CD24v) precedes immediately GPI anchorage site (position omega-1), determines CD24 loss activity. CD24v has been associated with multiple sclerosis and systemic lupus erythematous in other populations. OBJECTIVE: To find the presence of CD24v in Mexican patients with systemic lupus erythematous. MATERIAL AND METHOD: A study of fenotyping of CD24v included 65 subjects, 32 cases (systemic lupus erythematous): 28 women and 4 men; and 32 controls: 9 women and 23 men; cases and controls from patients with systemic lupus erythematous in National Medical Center 20 de Noviembre ISSSTE, Mexico City, services of Clinical Immunology and Rheumatology. RESULTS: In cases, 19 patients had a wild homozygous genotype, 12 were heterozygous and only one patient showed homozygous polymorphism. In controls, 17 showed wild heterozygous genotypes; 14 were heterozygous and 1 was found to be polymorphic homozygote. With odds ratio: 0.84 and chi-squared of 0.17; therefore there was no statistically significant difference. CONCLUSIONS: Study population showed that there is no statistically significant difference between systemic lupus erythematous cases and controls with respect to the presence of CD24v. PMID- 26556662 TI - [Prevalence of asthma and determination of symptoms as risk indicators]. AB - BACKGROUND: Asthma is a chronic inflammatory airway disease whose prevalence has increased, especially in developed countries; the results of studies of asthma prevalence vary in different populations and even within the same country; in Mexico we observed fluctuations in prevalence of asthma from 7% to 33%. OBJECTIVE: To determine the prevalence of asthma and severity of symptoms as risk indicators in school population in cities in various states of Mexico. MATERIAL AND METHOD: A descriptive study of detection of asthma prevalence and analytical comparative observational study of determination of symptoms of asthma. The surveys were applied to preschool, elementary, middle and high school population, in the cities of Puebla, Puebla; Tulancingo, Hidalgo; Tlaxcala, Tlaxcala, and Cancun, Quintana Roo; new validated questionnaire was used as instrument: Asthma Diagnostic Questionnaire for Epidemiologic Studies, consisting of eight questions with summation value for diagnosis. RESULTS: 8,754 surveys showed a 14% prevalence in Puebla, 17% in Tulancingo, 7% in Tlaxcala, and 14% in Cancun; average in four cities surveyed was 13%; the strength of association with asthma symptoms in descending order with significant odds ratio were: recurrent wheezing, breathlessness, chest tightness, recurrent cough, cough cold, recurrent cold symptoms, predominantly nocturnal cough, cough that increases with exercise. CONCLUSIONS: The average prevalence of asthma in the surveyed cities was 13% and the main symptoms indicators of risk of asthma in school children were: recurrent wheezing, breathlessness, chest tightness and recurrent cough. PMID- 26556663 TI - [Epidemiologic features in patients with antihistamine-resistant chronic urticaria]. AB - BACKGROUND: Current information on the particular features of patients suffering chronic spontaneous urticaria refractory to treatment is limited. OBJECTIVE: To investigate demographic and clinical characteristics in patients with refractory chronic spontaneous urticaria. MATERIAL AND METHODS: A retrospective analysis of the clinical and demographic information of patients consulting Allergy services from two hospitals in Caracas, Venezuela, who presented spontaneous urticaria lasting more than 6 weeks and did not respond to, at least, one course of treatment with antihistamines. RESULTS: Refractory chronic spontaneous urticaria was frequent in Hispanic female patients aged 20 to 59 years, with moderate symptoms, individual lesions lasting less than three hours, and wheal diameters between 1 and 3 cm. Angioedema, alone or associated to urticaria was present in 14% of the patients. Most frequent comorbidities were asthma, rhinitis and rhinosinusitis, thyroid diseases and hypertension. CONCLUSION: Refractory chronic spontaneous urticaria constitutes a highly prevalent subgroup of chronic urticaria which represents an important therapeutic challenge. This study did not demonstrate differential characteristics distinguishing refractory chronic spontaneous urticaria from chronic spontaneous urticaria patients who respond to the treatment with antihistamines. PMID- 26556664 TI - [Impact of air pollution on the development of asthma]. AB - Air pollution affects the origin and evolution of respiratory diseases. The increased frequency of asthma in recent years has been associated with growth air pollutants and small particles produced from the combustion of petroleum or cigarette smoke. Some mechanisms of how these contaminants can influence asthma and other allergic diseases are known: 1) acting as irritating on alveolar epithelial cells, 2) actin as adjuvant for allergens inflammation, 3) and epigenetic mechanisms. In this review, we discuss the pathophysiological mechanisms by which air pollutants become risk factors for the development of asthma and other allergic diseases. PMID- 26556665 TI - [Phenotypic and functional diversity of B lymphocytes]. AB - For many years, it has been considered that the function of B cells is only to serve as precursors of antibody-producing plasma cells; however, this simplistic view has been challenged in the past thirty years. The first big surprise came during the seventies, when it was shown that B lymphocytes are not a homogeneous population, but is made up of various subpopulations with different origin and functions, including both innate and acquired immunity. During the eighties, it was discovered that B cells are an important source of cytokines, extending its functions from antigen presentation to cooperation with T cells. From the year two thousand, it is clear that B cells are, functionally speaking, as heterogeneous as T lymphocytes, extending its functions to the regulation of the immune response. The story does not end yet, as they continue to discover new features that will have to be incorporated into the main body of knowledge about the mechanisms by which the immune response works. Thus, we can conclude by congratulating the B lymphocytes by these first 50 years and we can predict at least another 50 of robust growth. PMID- 26556666 TI - [The research protocol. Part I]. AB - One of the principal aims in research is the publication of the study in scientific journals. This implies two challenges: the first one, the election of an adequate research design, and the second one, the concrete and simple wording of the results for the study to be accepted in the most appropriate journal according to the scope. Despite numerous supporting documents are available for both issues, the publication process is long, tiresome, and can discourage the most enthusiastic researcher. This is the first of a series of articles with the objective to describe the steps from the research question to the publication of the study. First of all, the importance of the research design will be addressed. The structure of the protocol is essential to achieve the objectives, and provides a way to organize the investigation in a logic, comprehensible and efficient manner. PMID- 26556667 TI - [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient]. AB - Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production. PMID- 26556668 TI - [Bullous systemic lupus mimicking a Stevens-Johnson syndrome]. AB - Autoimmune bullous diseases represent a diagnostic challenge due to the wide spectrum of pathologies that share similar clinical features. This paper reports the case of a woman admitted with a supposed diagnosis of a Stevens-Johnson syndrome, in which the history, the profile of autoimmunity and interdisciplinary approach were of vital importance to clarify the clinical picture. PMID- 26556669 TI - Oncocytic osteolipoadenoma of the submandibular gland. PMID- 26556671 TI - Both Systemic and Pulmonary Artery Stiffness Predict Ventricular Functional Recovery after Successful Percutaneous Closure of Atrial Septal Defects in Adults. AB - BACKGROUND: Percutaneous closure of atrial septal defect (ASD) has become the preferred method in treatment of the majority of cases. The aim of this study was to evaluate the echocardiographic effects of percutaneous closure of secundum ASD in adults and assess which parameters predict good response to closure. DESIGN: We prospectively included 42 patients with secundum ASD treated successfully with percutaneous device closure. All patients underwent transthoracic echocardiography examination with tissue Doppler imaging before, 24 hours after and within 3 months of intervention. Measurements of arterial stiffness were carried out using a Mobil-O-Graph arteriography system. RESULTS: Remodeling of heart chambers occurred immediately and persisted at 3 months after ASD closure. Significant decreases were observed in right ventricle (RV) end-diastolic diameter, right atrium volume index, and tricuspid annular plane systolic excursion both after the procedure and at 3 months (P < .01 for all). The RV and left ventricle (LV) tissue Doppler-myocardial performance index demonstrated to decline during follow up (P = .0001). Significant correlations were found between pulse-wave velocity, augmentation index, pulmonary artery stiffness, and LV-RV tissue Doppler-myocardial performance index at third month. Linear regression analyses showed that pulse-wave velocity is the most effective parameter of LV and pulmonary artery stiffness is the most effective parameter of RV functional recovery, respectively, assessed by tissue Doppler-myocardial performance index. CONCLUSIONS: Percutaneous closure of secundum ASD in adults has various sustained benefits on multiple echocardiographic parameters within 3 months. The changes in RV and LV function after device closure were significantly correlated with the degree of pulmonary artery stiffness and pulse-wave velocity, respectively. PMID- 26556672 TI - Occupational exposures to influenza among healthcare workers in the United States. AB - The objective of this study is to estimate the annual number of occupational exposures to influenza among healthcare workers that result from providing direct and supportive care to influenza patients in acute care, home care and long-term care settings. Literature review was used to identify healthcare utilization for influenza, and worker activity patterns. This information was used, with Monte Carlo simulation, to tabulate the mean annual number of occupational exposures. Given a medium-sized epidemic with a 6% annual symptomatic influenza incidence proportion, the mean number of occupational exposures was estimated to be 81.8 million annually. Among the approximately 14 million healthcare workers, this corresponds to 5.8 exposures per worker annually, on average. Exposures, however, are likely concentrated among subsets of healthcare workers. Occupational exposures were most numerous in ambulatory care settings (38%), followed by long term care facilities (30%) and home care settings (21%). The annual number of occupational exposures to influenza is high, but not every occupational exposure will result in infection. Some infection control activities, like patient isolation, can reduce the number of occupational exposures. PMID- 26556670 TI - Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms. AB - Neurodegenerative human CJD and sheep scrapie are diseases caused by several different transmissible encephalopathy (TSE) agents. These infectious agents provoke innate immune responses in the brain, including late-onset abnormal prion protein (PrP-res) amyloid. Agent particles that lack detectable PrP sequences by deep proteomic analysis are highly infectious. Yet these agents, and their unusual resistance to denaturation, are often evaluated by PrP amyloid disruption. To reexamine the intrinsic resistance of TSE agents to denaturation, a paradigm for less resistant viruses and microbes, we developed a rapid and reproducible high yield agent isolation procedure from cultured cells that minimized PrP amyloid and other cellular proteins. Monotypic neuronal GT1 cells infected with the FU-CJD or 22L scrapie agents do not have complex brain changes that can camouflage infectious particles and prevent their disruption, and there are only 2 reports on infectious titers of any human CJD strain treated with chemical denaturants. Infectious titers of both CJD and scrapie were reduced by >4 logs with Thiourea-urea, a treatment not previously tested. A mere 5 min exposure to 4M GdnHCl at 22 degrees C reduced infectivity by >5 logs. Infectious 22L particles were significantly more sensitive to denaturation than FU-CJD particles. A protocol using sonication with these chemical treatments may effectively decontaminate complicated instruments, such as duodenoscopes that harbor additional virulent microbes and biofilms associated with recent iatrogenic infections. PMID- 26556673 TI - Plasma nanotextured polymeric lab-on-a-chip for highly efficient bacteria capture and lysis. AB - We describe the design, fabrication, and successful demonstration of a sample preparation module comprising bacteria cell capture and thermal lysis on-chip with potential applications in food sample pathogen analysis. Plasma nanotexturing of the polymeric substrate allows increase of the surface area of the chip and the antibody binding capacity. Three different anti-Salmonella antibodies were directly and covalently linked to plasma treated chips without any additional linker chemistry or other treatment. Then, the Ab-modified chips were tested for their capacity to bind bacteria in the concentration range of 10(2)-10(8) cells per mL; the module exhibited 100% efficiency in Salmonella enterica serovar Typhimurium bacteria capture for cell suspensions below 10(5) cells per mL (10(4) cells injected with a 100 MUL sample volume) and efficiency higher than 50% for 10(7) cells per mL. Moreover, thermal lysis achieved on-chip from as low as 10 captured cells was demonstrated and shown to compare well with off-chip lysis. Excellent selectivity (over 1 : 300) was obtained in a sample containing, in addition to S. Typhimurium and E. coli bacteria. PMID- 26556674 TI - Cervical length as a predictor for spontaneous preterm birth in high-risk singleton pregnancy: current knowledge. PMID- 26556675 TI - Validation of ion channel targets. AB - A prerequisite for a successful target-based drug discovery program is a robust data set that increases confidence in the validation of the molecular target and the therapeutic approach. Given the significant time and resource investment required to carry a drug to market, early selection of targets that can be modulated safely and effectively forms the basis for a strong portfolio and pipeline. In this article we present some of the more useful scientific approaches that can be applied toward the validation of ion channel targets, a molecular family with a history of clinical success in therapeutic areas such as cardiovascular, respiratory, pain and neuroscience. PMID- 26556676 TI - Responsive stimulation of motor cortex for medically and surgically refractive epilepsy. PMID- 26556677 TI - Combined detection of depression and anxiety in epilepsy patients using the Neurological Disorders Depression Inventory for Epilepsy and the World Health Organization well-being index. AB - PURPOSE: To validate the Danish version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and compare it with the World Health Organization index for psychological well-being (WHO-5) as screening tests for depression and anxiety in epilepsy patients. METHODS: Epilepsy outpatients filled out NDDI-E and WHO-5. A Mini International Neuropsychiatric Interview (MINI) as gold standard for psychiatric diagnoses was carried out with every patient. RESULTS: We included 124 epilepsy patients. According to MINI, 5% had depression without anxiety, 6% anxiety without depression, and 6% had both. For the detection of depression, NDDI-E was slightly better than WHO-5. With a score of more than 13, NDDI-E as a screening tool for depression had a sensitivity of 0.92, a specificity of 0.84, a positive predictive value (PPV) of 0.40, and a negative predictive value (NPV) of 0.99. In the detection of anxiety WHO-5 was better than NDDI-E. With a score below 50, WHO-5 as screening for anxiety had a sensitivity of 0.80, a specificity of 0.92, PPV 0.57, and NPV 0.97. When combining NDDI-E>13 and WHO-5<50, 95% of patients with depression and/or anxiety are identified, and in addition there are 17% false positives. CONCLUSION: NDDI-E in Danish is valid and slightly better than WHO-5 in the detection of depression in epilepsy patients. WHO-5 is valid for the detection of anxiety disorders. Combined use of NDDI-E and WHO-5 is recommended, since 95% of all epilepsy patients with depression and/or anxiety disorder are identified with only a modest number of false positives. PMID- 26556679 TI - Fat middle section is less healthy than being obese, say researchers. PMID- 26556678 TI - Aortic stiffness is an independent determinant of left ventricular diastolic dysfunction in metabolic syndrome patients. AB - BACKGROUND: We aimed to evaluate the relationship between arterial stiffness and left ventricular diastolic dysfunction (LVDD) in metabolic syndrome (MetS) patients. METHODS: A cross-sectional study was conducted in 1208 subjects without overt atherosclerotic disease. According to the cardiac ultrasound, patients were divided into two groups: with LVDD (LVDD+, n = 1119) and without LVDD (LVDD-, n = 89). Arterial stiffness parameters [carotid-femoral pulse wave velocity (cfPWV) and aortic augmentation index (AIxHR75)] were assessed by applanation tonometry. RESULTS: In comparison to LVDD-, LVDD + patients were older (55 +/- 6 vs 51 +/- 6 years, p < 0.001), and had higher cfPWV (8.8 +/- 1.6 vs 7.9 +/- 1.34 m/s, p < 0.001), AIxHR75 (24.7 +/- 10.2 vs 19.7 +/- 10, p < 0.001), mean arterial pressure (108 +/- 12 vs 101 +/- 10 mmHg, p < 0.001), heart rate (66 +/- 10 vs 61 +/- 9 bpm, p < 0.001), left ventricular mass index (LVMI) (109 +/- 24 vs 97 +/- 22, p < 0.001) and body mass index (BMI) (32 +/- 5 vs 30 +/- 4 kg/m(2), p < 0.001). We found significant correlations between cfPWV, AIxHR75 and the ratio of early to late transmitral velocities (E/A) (rcfPWV = -0.19, rAIxHR75 = -0.15, p < 0.001), early diastolic mitral annular velocity (E') (rcfPWV = -0.25, rAIxHR75 = -0.18, p < 0.05) and E/E' ratio (rcfPWV = 0.17, rAIxHR75 = 0.14, p < 0.001). Univariate analysis revealed that the presence of LVDD is associated with age [odds ratio (OR) 1.84], BMI (OR 1.63), waist circumference (WC) (OR 1.52), cfPWV (OR 2.18), AIxHR75 (OR 1.55), mean aortic blood pressure (OR 1.94), aortic pulse pressure (OR 1.78), mean common carotid artery intima-media thickness (OR 1.16), heart rate (OR 1.4) and LVMI (OR 1.79) (all p < 0.05). After performing stepwise multiple logistic regression analysis, only cfPWV and BMI or WC remained significant predictors of the presence of LVDD (p < 0.05). CONCLUSION: cfPWV is a significant determinant of LVDD in subjects with MetS. PMID- 26556680 TI - Some selected quantitative methods of thermal image analysis in Matlab. AB - The paper presents a new algorithm based on some selected automatic quantitative methods for analysing thermal images. It shows the practical implementation of these image analysis methods in Matlab. It enables to perform fully automated and reproducible measurements of selected parameters in thermal images. The paper also shows two examples of the use of the proposed image analysis methods for the area of the skin of a human foot and face. The full source code of the developed application is also provided as an attachment. The main window of the program during dynamic analysis of the foot thermal image. PMID- 26556681 TI - Inhibitory Effect of Cinnamaldehyde, Citral, and Eugenol on Aflatoxin Biosynthetic Gene Expression and Aflatoxin B1 Biosynthesis in Aspergillus flavus. AB - In order to reveal the inhibitory effects of cinnamaldehyde, citral, and eugenol on aflatoxin biosynthesis, the expression levels of 5 key aflatoxin biosynthetic genes were evaluated by real-time PCR. Aspergillus flavus growth and AFB1 production were completely inhibited by 0.80 mmol/L of cinnamaldehyde and 2.80 mmol/L of citral. However, at lower concentration, cinnamaldehyde (0.40 mmol/L), eugenol (0.80 mmol/L), and citral (0.56 mmol/L) significantly reduced AFB1 production with inhibition rate of 68.9%, 95.4%, and 41.8%, respectively, while no effect on fungal growth. Real-time PCR showed that the expressions of aflR, aflT, aflD, aflM, and aflP were down-regulated by cinnamaldehyde (0.40 mmol/L), eugenol (0.80 mmol/L), and citral (0.56 mmol/L). In the presence of cinnamaldehyde, AflM was highly down-regulated (average of 5963 folds), followed by aflP, aflR, aflD, and aflT with the average folds of 55, 18, 6.5, and 5.8, respectively. With 0.80 mmol/L of eugenol, aflP was highly down-regulated (average of 2061-folds), followed by aflM, aflR, aflD, and aflT with average of 138-, 15-, 5.2-, and 4.8-folds reduction, respectively. With 0.56 mmol/L of citral, aflT was completely inhibited, followed by aflM, aflP, aflR, and aflD with average of 257-, 29-, 3.5-, and 2.5-folds reduction, respectively. These results suggest that the reduction in AFB1 production by cinnamaldehyde, eugenol, and citral at low concentration may be due to the down-regulations of the transcription level of aflatoxin biosynthetic genes. Cinnamaldehyde and eugenol may be employed successfully as a good candidate in controlling of toxigenic fungi and subsequently contamination with aflatoxins in practice. PMID- 26556682 TI - [Persistent Perpetrator Contact in a Patient with Dissociative Identity Disorder]. AB - The case of a young woman with still ongoing incest and forced prostitution is presented. The criteria for a dissociative identity disorder (DID) were met. Due to persistent contact to the perpetrator she was repeatedly revictimized. Based on the model of trauma-related dissociation we discuss to what extent she was capable of self-determined decision making as well as therapeutic consequences resulting therefrom. PMID- 26556683 TI - [Job Satisfaction Among Young Physicians Working in Psychiatric and Psychosomatic Care - Results of a Survey in Saxony, Germany]. AB - Objective: Analysis of job satisfaction and intentions to quit among physicians working in psychiatric/psychosomatic care compared to physicians working in somatic care. Methods: Full postal survey of all physicians <= 40 years of age registered with the State Chamber of Physicians of Saxony (response rate 40 %, n = 2357). Analysis was restricted to physicians working in patient care (n = 1901). Results: Physicians working in psychiatric/psychosomatic care as well as those in somatic care were rather satisfied with their overall job situation (mean: 3.48 [standard deviation: 1.01] vs. 3.40 [0.94], 5 point Likert scale). Physicians working in psychiatric/psychosomatic care were less satisfied with only 2 out of 20 aspects of job satisfaction. Nearly a quarter wished to leave patient care or to go abroad, which did not differ from physicians working in somatic care. Conclusion: The present study did not confirm international results indicating lower job satisfaction among psychiatrists. PMID- 26556684 TI - [Improving Mental Health Care in People at Risk for Getting Homeless]. AB - Objective: Overall aim was to reduce the untreated prevalence in persons with untreated mental disorders and at risk for loosing accommodation and descending into homelessness. Primary aim was treatment initiation and treatment adherence by motivational interviewing. Secondary aims were to reduce social or financial problems. Methods: Persons at risk were identified in social welfare services or labour agencies, diagnosed and motivated to initiate treatment in a community mental health service. Results: 58 persons were included, 24 were referred to regular mental health care, 8 were stabilized enough after the initial motivational to refrain from acute treatment, 26 dropped out. During a 6-month follow-up quality of life and social support was improved (partly statistically significant) and psycho-social needs for care decreased. Conclusion: Motivational interviewing is likely to increase insight into illness and acceptance of mental health care in untreated persons with mental disorders at risk for social decline. PMID- 26556685 TI - [Assessment of Functioning when Conducting Occupational Capacity Evaluations- What is "Evidence-Based"?]. AB - AIM: Occupational capacity evaluations have previously been subject to criticism for lacking in quality and consistency. To the authors' knowledge, there is no clear consensus on the best way to formally assess functioning within capacity evaluations. In this review we investigated different instruments that are used to assess functioning in occupational capacity evaluations. METHODS: Systematic review of the literature. RESULTS: Though several instruments that assess functional capacity were found in our search, a specific validated instrument assessing occupational capacity as part of a larger psychiatric evaluation was not found. The limitations of the existing instruments on assessing functional capacity are discussed. CONCLUSION: Medical experts relying on instruments to conduct functional capacity evaluations should be cognizant of their limitations. The findings call for the development and use of an instrument specifically designed to assess the functional and occupational capacity of psychiatric patients, which is also likely to improve the quality of these reports. PMID- 26556686 TI - [Which Working Conditions Promote the Development of Depressive Disorders?]. AB - BACKGROUND: Epidemiological and neurobiological research suggests an association between stress and the development of depression. In this context, the question arises whether certain working conditions do act as depressogenic stressors. METHOD: We systematically reviewed cross-sectional and prospective studies (published since 2005) investigating the association between working conditions and the occurrence of depression. Moreover, meta-analyses on reported effect sizes were calculated. RESULTS: Our meta-analyses confirmed a depressogenic effect of high job demands and the combination of high demands and low job control ("Job Strain"). We did not find an effect of low job control alone. The impact of these working conditions is modulated by contextual factors like occupational grade or cognitive coping strategies. CONCLUSION: Based on these results, we suggest an extended model of working conditions, coping capacities, and their relation to the development of depression. This can be utilized for strategies of occupational prevention and individual therapy. PMID- 26556687 TI - Comparison of Continuous Noninvasive Blood Pressure Monitoring by TL-300 With Standard Invasive Blood Pressure Measurement in Patients Undergoing Elective Neurosurgery. AB - BACKGROUND: Intraoperative blood pressure (BP) is one of the basic vital signs monitoring. Compared with standard invasive BP measurement, TL-300 allows for a continuous and beat-to-beat noninvasive intraoperative BP monitoring. The current retrospective study compared the accuracy and precision of this noninvasive technique for continuous BP monitoring with that of standard invasive BP measurement in patients undergoing elective neurosurgery. MATERIALS AND METHODS: BP records of 23 patients undergoing elective neurosurgery, measured by both noninvasive TL-300 and invasive radial arterial catheter method, were retrospectively analyzed. Variability in BP data was analyzed by using linear regressions and Bland-Altman analysis. RESULTS: Four thousand three hundred eighty-one pairs of BP measurements from a total of 23 patients were included. The coefficient of determination of systolic, diastolic, and mean BP were 0.908, 0.803, and 0.922, respectively. And their bias was found to be 1.3+/-5.87 mm Hg (95% limits of agreement: -10.2 to +12.8 mm Hg), 2.8+/-6.40 mm Hg (95% limits of agreement: -9.8 to +15.3 mm Hg), and 1.8+/-4.20 mm Hg (95% limits of agreement: 6.4 to +10.1 mm Hg), respectively. CONCLUSIONS: TL-300 system is a promising noninvasive alternative to the invasive arterial catheter method for intraoperative BP monitoring, with a high accuracy and precision. With the limitation of the current retrospective study, further prospective method comparison studies are needed. PMID- 26556688 TI - Genetic variation in IL-1beta, IL-2, IL-6, TSPO and BDNF and response to duloxetine or placebo treatment in major depressive disorder. AB - AIM: This study investigated polymorphisms of five inflammatory-related genes for association with duloxetine and placebo response in patients with major depression. PATIENTS & METHODS: Twenty SNPs in IL-1beta, IL-2, IL-6, TSPO and BDNF were genotyped in major depressive disorder patients treated with either duloxetine (n = 215) or placebo (n = 235) for up to 8 weeks. Treatment response was measured with the Montgomery-Asberg Depression Rating Scale. RESULTS: IL-6 variants rs2066992 and rs10242595 were nominally associated with response to duloxetine (p = 0.047 and p = 0.028, respectively). Notably, the variant rs2066992 was also associated with placebo response (p = 0.026). However, none of our results remained significant after correction for multiple testing. CONCLUSION: Our findings tentatively suggest that IL-6 variants play a role in duloxetine and placebo response, which warrants further investigation. PMID- 26556689 TI - A theoretical biogenesis overview of diterpenes isolated from Salvia microphylla. AB - Establishing the reaction mechanisms involved in the biosynthesis of natural products plays an important role in phytochemistry and pharmacology. Mechanistic studies of the biogenesis of natural products have been mainly explored by means of theoretical calculations, and taking into account experimental structures of reagents and products. Using a hybrid meta density functional theory method (mPW1B95), we studied the mechanisms associated with the biogenesis of five neo clerodanes isolated from Salvia mycrophylla. The reaction mechanisms presented here explain the formation of the five neo-clerodanes and coincides with the formulated biogenetic hypothesis. Graphical Abstract Proposed biogenesis of diterpenes isolated from Salvia microphylla. PMID- 26556690 TI - Long-term remission of therapy-related acute myeloid leukemia with a new t(11;18)(q23;q21.2) translocation and KMT2A-ME2 (MLL-ME2) fusion gene. AB - We describe a unique case of a woman with acute myeloid leukemia with a new, previously undescribed translocation, t(11;18)(q23;q21.2), affecting the KMT2A (MLL) gene and resulting in an KMT2A(MLL)-ME2 fusion. This disease occurred secondarily following chemotherapy for a different acute myeloid leukemia with the recurrent genetic abnormality inv(16)(p13.1;q22). The secondary leukemia was treated with intensive chemotherapy without allogeneic hematopoietic cell transplantation. Complete remission lasting more than 10 years has been achieved with concurrent and sustained remission of the primary leukemia. PMID- 26556691 TI - Tumor heterogeneity uncovered by dynamic expression of long noncoding RNA at single-cell resolution. AB - The expression of long noncoding RNA (lncRNA) is thought to be more cell-type specific than the expression of protein-coding genes. However, the expression profile of individual cells regarding lncRNA remains to be elucidated. Here, we comprehensively investigated the pattern of lncRNA expression across five glioblastoma tumors (414 cells) and two cell lines (GBM6 and GBM8, 127 cells). We found that there were more than 1,000 lncRNAs that varied between any two cells and that there was frequent gain and loss of lncRNA expression during tumor cell proliferation, suggesting a great heterogeneity in lncRNA expression across different single cells in glioblastoma. PMID- 26556692 TI - One year of free school fruit in Norway--7 years of follow-up. AB - BACKGROUND: It is important that health-promoting efforts result in sustained behavioural changes, preferably throughout life. However, only a very few intervention studies evaluate long term follow up. OBJECTIVE: The aim of the present study is to evaluate the overall and up to seven years effect of providing daily one piece of fruit or vegetable (FV) for free for one school year. METHODS: A total of 38 randomly drawn elementary schools from two counties in Norway participated in the Fruit and Vegetables Make the Marks project. Baseline (2001) and follow-up surveys were conducted in May 2002, 2005 and 2009 (n = 320 with complete data) to assess FV and unhealthy snack intake. Mixed models were used to analyze the data. RESULTS: Statistically significant adjusted overall effects of the intervention were revealed for FV intake (1.52 times/day) but this weakened over time. A significant adjusted overall effect (-1.54 consumptions/week) and a significant seven-year-follow-up effect (-2.02 consumptions/week) was found for consumption of unhealthy snacks for pupils of parents without higher education. CONCLUSION: One year of free school fruit resulted in higher FV intake and lower unhealthy snack intake, however this weakened over time for FV intake and became stronger for snack intake. More follow-up studies with larger samples and lower attrition rates are needed in order to further evaluate the long-term effect. PMID- 26556693 TI - Early onset of nontuberculous mycobacterial pulmonary disease contributes to the lethal outcome in lung transplant recipients: report of two cases and review of the literature. AB - Lung transplant (LuTx) recipients represent a population at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD). Yet the risk factors, the timing of NTM-PD after transplantation, and the association with allograft dysfunction all remain poorly defined. We report 2 cases of early-onset NTM-PD and review the literature, focusing on NTM-PD in LuTx recipients not colonized with NTM prior to transplantation. In addition, we summarize the main characteristics and differences between early- and late-onset disease. PMID- 26556694 TI - Genetic analysis of the rates of conception using a longitudinal threshold model with random regression in dairy crossbreeding within a tropical environment. AB - This study was designed to: (i) estimate genetic parameters and breeding values for conception rates (CR) using the repeatability threshold model (RP-THM) and random regression threshold models (RR-THM); and (ii) compare covariance functions for modeling the additive genetic (AG) and permanent environmental (PE) effects in the RR-THM. The CR was defined as the outcome of an insemination. A data set of 130 592 first-lactation insemination records of 55 789 Thai dairy cows, calving between 1996 and 2011, was used in the analyses. All models included fixed effects of year * month of insemination, breed * day in milk to insemination class and age at calving. The random effects consisted of herd * year interaction, service sire, PE, AG and residual. Variance components were estimated using a Bayesian method via Gibbs sampling. Heritability estimates of CR ranged from 0.032 to 0.067, 0.037 to 0.165 and 0.045 to 0.218 for RR-THM with the second, third and fourth-order of Legendre polynomials, respectively. The heritability estimated from RP-THM was 0.056. Model comparisons based on goodness of fit, predictive abilities, predicted service results of animal, and pattern of genetic parameter estimates, indicated that the model which fit the desired outcome of insemination was the RR-THM with two regression coefficients. PMID- 26556695 TI - Introduction to the 'VEINS' supplement. PMID- 26556696 TI - Varicose veins--Who should be referred? AB - Varicose veins are a common, progressive condition in the UK, with significant negative effects on patients' quality of life. Despite their prevalence, access to secondary care for the assessment and treatment of varicose veins can be variable throughout the country.The National Institute of Health and Care Excellence guidelines developed in 2013 provide evidence-based guidance on the referral, assessment, and management of the patient with venous disease.In this article, we review the development of the guidelines for the management of varicose veins over the last 15 years, highlighting the latest changes in referral criteria. PMID- 26556697 TI - Radiofrequency ablation of varicose veins: Best practice techniques and evidence. AB - SCOPE OF THE REVIEW: This article systematically reviews the practice of radiofrequency ablation of lower limb varicose veins. We present the clinical evidence and best practice techniques for currently available devices. METHODS: Manufacturer's instructions-for-use were requested for all radiofrequency devices. The MEDLINE and EMBASE databases were searched using the following keywords: 'varicose veins' AND 'radiofrequency' OR 'radio frequency' OR 'Venefit' OR 'ClosureFAST' OR 'RFiTT' OR 'EVRF' OR 'VeinCLEAR', generating 240 articles. Titles and abstracts were screened, yielding 63 articles directly relevant to the scope of the review. Reference lists for publications were also searched to identify further manuscripts of relevance. The Cochrane Database and current National Institute for Clinical and Healthcare Excellence guidelines for varicose veins were also searched from relevant articles. RESULTS: Four radiofrequency ablation (RFA) systems are currently commercially available. Generic practice methods (common to all RF systems) and device-specific techniques are described. The weight of current evidence relates to the use of Covidien VenefitTM (formerly VNUS ClosureFASTTM), which clearly demonstrates clinical advantages over open surgery at least to 2 years follow up. However, contemporary studies of the radiofrequency-induced thermal therapy device (RFiTT(r)), show that in experienced hands, clinical equivalence to the VenefitTM procedure can be achieved. The evidence base for EVRF(r) and VeinCLEARTM devices is currently weak and absent, respectively. CONCLUSIONS: Despite widespread uptake of RFA and acceptance of its clinical advantages over open surgery there is a paucity of Class 1 A evidence. This results from incongruent reporting of clinical outcome measures within existing literature. Similarly, lack of long-term follow-up studies precludes comparison of the durability of short- and medium-term advantages of RFA with the longer term results of open surgery. There remains scope for a large prospective high-quality trial to assess the clinical, anatomical and cost-effectiveness outcomes for the four commercially available RFA devices, with a particular focus on long-term follow up. PMID- 26556698 TI - Foam sclerotherapy. AB - Foam sclerotherapy is a minimally invasive treatment for lower limb varicose veins. Current evidence indicates that its efficacy may not be as high as surgery or endovenous ablation. The minimally invasive nature of the treatment however means that it has a wide application, and it can be particularly useful in patients who are not suitable for other types of treatment. NICE guidelines recommend its use as a second line after endovenous ablation. Complication rates are low and most of these are of little clinical consequence. PMID- 26556699 TI - Glue, steam and Clarivein--Best practice techniques and evidence. AB - In July 2013, the National Institute of Health and Clinical Excellence (NICE) recommended "endothermal" ablation (meaning endovenous thermal ablation) is the first line treatment for truncal venous reflux in varicose veins. The initial endovenous thermoablation devices were radiofrequency ablation and endovenous laser ablation. More recently, Glue (cyanoacrylate), endovenous steam and Clarivein (mechanochemical ablation or MOCA) have entered the market as new endovenous techniques for the treatment of varicose veins. Glue and Clarivein do not require tumescent anaesthesia and do not use heat and therefore termed non tumescent non-thermal (NTNT). Steam both requires tumescence and is also a thermal technique (TT). This article reviews the current position of these 3 new technologies in the treatment of varicose veins. PMID- 26556700 TI - Is there a continuing role for traditional surgery? AB - Despite recent NICE guidance there remains a definite role for surgery in the management of varicose veins. A lot of the available evidence that has driven the transformation of care towards endovenous treatments is of good quality yet published by enthusiasts. No endovenous studies have reported long term results as far out from intervention as the open studies, yet in the meta-analysis from Murad et al, the authors suggested from their results that when surgery was compared with all endoluminal ablation therapies, surgery was associated with a non-significant reduction in the risk of varicose vein recurrence (RR0.63; 95%CI 0.37--1.07). Much of the longer-term data on recurrence following open surgery for primary varicose veins dates back well over 15 years ago. This is prior to the inclusion of routine duplex assessment and sub-specialty designation. The recent Cochrane review (13 randomised controlled studies, 3081 patients). The overall conclusion was that UGFS, EVLT and RFA were at least as effective as surgery in the treatment of the LSV. This meta-analysis did not include the CLASS (Comparison of LAser, Surgery and foam Sclerotherapy as a treatment for varicose veins) trial in which measures of clinical success were similar among the groups. Only 48% of the patients screened were eligible for the CLASS study and of these, only 24% of the eligible patients agreed to take part in the study. Similarly in the study by Carradice out of a total of 772 patients assessed for suitability, 442 did not meet the inclusion criteria. There is no doubt that endovenous surgery will increasingly become first line treatment for patients with symptomatic superficial venous reflux specifically in patients with SSV reflux. However, given the device related limitations with endothermal techniques specifically with regard to adverse anatomical features allied to the poorer results of UGFS within the treatment of LSV reflux, there is without doubt still a role for more traditional open surgical techniques that can be delivered with good short and long term outcomes and still being delivered in a cost effective manner. PMID- 26556701 TI - Laser; best practice techniques and evidence. AB - Laser ablation involves the delivery of laser light through a glass fibre placed into the lumen of a refluxing vein. This energy is converted into heat inducing a permanent, non-thrombotic occlusion. This highly effective and safe approach has significant advantages over traditional surgical treatment and has driven the endovenous revolution in the management of varicose veins. This chapter will explore the mechanism of action, present the evidence of laser' clinical and cost effectiveness, and analyse specific and generic aspects of laser ablation technique. PMID- 26556702 TI - CHIVA, ASVAL and related techniques--Concepts and evidence. AB - Chronic venous disease (CVD) is a highly prevalent condition with significant effects on patients' quality of life. Despite this, the underlying pathophysiology of venous disease still remains unclear. Two schools of thought exist, explaining the development and propagation of venous disease as an "ascending" and "descending" process, respectively. The descending theory, stating that CVD is secondary to proximal disease (e.g. saphenofemoral/saphenous incompetence), is the most widely accepted when planning treatment aiming to remove or destroy the junction or truncal veins. The ascending theory, describing the disease process as developing in the lower most part of the leg and propagating cranially, aims to re-route the venous circulation via minimally invasive interventions. Classically, superficial venous insufficiency has been treated with the removal of the incompetent trunk, via open surgery or, increasingly, with endovenous interventions. Minimally invasive treatment modalities aiming to preserve the saphenous trunk, such as CHIVA and ASVAL, may also play an important role in the treatment of the patient with varicose veins. PMID- 26556703 TI - Management of reticular veins and telangiectases. AB - AIM: To review the literature related to the management of reticular varices and telangiectases of the lower limbs to provide guidance on the treatment of these veins. FINDINGS: Very few randomised clinical trials are available in this field. A European Guideline has been published on the treatment of reticular varices and telangiectases, which is largely based on the opinion of experts. Older accounts written by individual phlebologists contain extensive advice from their own practice, which is valuable in identifying effective methods of sclerotherapy. All accounts indicate that a history should be taken combined with a clinical and ultrasound examination to establish the full extent of the venous disease. Sclerotherapy is commenced by injecting the larger veins first of all, usually the reticular varices. Later in the same session or in subsequent sessions, telangiectases can be treated by direct injection. Following treatment, the application of class 2 compression stockings for a period of up to three weeks is beneficial but not used universally by all phlebologists. Further sessions can follow at intervals of 2-8 weeks in which small residual veins are treated. Resistant veins can be managed by ultrasound-guided injection of underlying perforating veins and varices. Other treatments including RF diathermy and laser ablation of telangiectases have very limited efficacy in this condition. CONCLUSIONS: Sclerotherapy, when used with the correct technique, is the most effective method for the management of reticular varices and telangiectases. PMID- 26556704 TI - Students' and teachers' experiences of participating in the reflection process "THiNK". AB - OBJECTIVES: Reflective journal writing in clinical practice is used as a tool in bachelor programs in nursing. The reflection process THiNK was developed to enhance students' reflection processes. It was tailored to the needs of a nursing programme (in Norway) as former studies showed that many students had superficial level of reflection in their reflective journals, few students applied knowledge to their reflections and some met unprepared in the guided reflection groups. The teachers had inconsistent focus on the importance of reflection as a way of learning. This study aimed to describe students' and teachers' experiences of participation in reflection processes. DESIGN AND METHOD: The development of THiNK is inspired by educational design research. This study used focus groups to gain insight into students' and teachers' experiences of the reflection processes. Data were analysed using qualitative content analysis. PARTICIPANTS AND SETTING: The empirical sample included 5 focus groups with 28 students and 7 teachers in a bachelor nursing program at a University College in Norway. RESULTS: The themes were as follows: stop and verbalise the experiences, stimulate and support the reflection processes and develop a conscious attitude. The students became aware of themselves and their own execution. The teachers and reflection groups were crucial in order to learn to see the complexity of a given situation and helped draw connection between the situation and the theoretical knowledge. CONCLUSIONS: Enhancing students' professional development requires attention to facilitation skills as well as other contextual factors. Readiness in the culture can be ensured by tailoring frameworks of reflection that replies to students' and teachers' requests. Participating in reflection processes facilitates integration of modes of thinking when dealing with clinical situations. PMID- 26556705 TI - Satisfaction with nursing education, job satisfaction, and work intentions of new graduate nurses. AB - BACKGROUND AND OBJECTIVE: In the context of predictions of future shortages of nurses, retaining new graduate nurses in the nursing workforce is essential to ensure sufficient nurses in the future. This paper investigates the links between satisfaction with nursing education and job satisfaction, and job dissatisfaction and intentions to leave a nursing job. DESIGN AND DATA SOURCES: It uses survey data from a cohort study of nursing students recruited through two Australian universities and followed after graduation and workforce entry. METHOD: Structural equation modeling (SEM) was used to simultaneously estimate the impact of educational satisfaction (work preparation component) on job satisfaction and the impact of job satisfaction on the expectation of leaving the current job. RESULTS: Two job satisfaction sub-scales were identified: 1) work environment satisfaction and 2) work hours and wages satisfaction. Work preparation satisfaction was significantly and positively associated with both job satisfaction scales but only work environment satisfaction was significantly associated with the expectation to stay in the job; a one standard deviation increase in work environment satisfaction was associated with a 13.5 percentage point reduction in the probability of expecting to leave. The estimated effect of satisfaction with education on expecting to leave, occurring indirectly through job satisfaction, was small (reducing the probability by less than 3 percentage points for a 1 point increase in work preparation satisfaction). Participating in a graduate transition program had the largest effect, reducing the probability of expecting to leave by 26 percentage points, on average. CONCLUSIONS: The study results suggest policies which focus on improving satisfaction with the work environment would be more effective at retaining nurses early in their career than improvements to conditions such as work hours and wages. Investment in new graduate transition programs would potentially have the largest impact on retention. PMID- 26556706 TI - Understanding pre-registration nursing fitness to practise processes. AB - BACKGROUND: Protection of the public is a key aspect of pre-registration nursing education and UK Nursing and Midwifery Council monitoring processes. Universities must ensure that nursing students are "fit to practise" both during their programme and at the point of registration. However, current evidence suggests that institutional fitness to practise policies and processes can be inconsistent, lacking in clarity, and open to legal challenge. OBJECTIVES: To examine fitness to practise processes in pre-registration nursing programmes in Scotland. PARTICIPANTS: Academic personnel (n=11) with key roles in fitness to practise processes in nine of the eleven Scottish universities providing pre registration nursing programmes. METHODS: Semi-structured qualitative interviews were conducted with eleven academics with responsibility for fitness to practise processes in pre-registration programmes. The qualitative data and documentary evidence including institutional policies and processes were thematically analysed. FINDINGS: In this paper, we focus on illuminating the key theme of Stages and Thresholds in Fitness to Practise processes i.e. Pre-fitness to practise, Stage 1, Stage 2, and Appeal, along with two thresholds (between Pre fitness to practise and Stage 1; between Stage 1 and Stage 2. CONCLUSIONS: Diverse fitness to practise processes are currently in place for Scottish pre registration nursing students. These processes draw on a shared set of principles but are couched in different terminology and vary according to their location within different university structures. Nevertheless, universities appear to be confronting broadly similar issues around ensuring fitness to practise and are building a body of expertise in this area. Examples of good practice are identified and include the use of staged processes and graduated outcomes, the incorporation of teaching about fitness to practise into nursing programmes, positive attitudes around health and disability, and collaborative decision making. Areas of challenge include systems for student support and consistent, equitable, and auditable fitness to practise processes. PMID- 26556707 TI - Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats. AB - BACKGROUND: Angiotensin-(1-7) [Ang-(1-7)] counteracts many actions of the renin angiotensin-aldosterone system. Despite its renoprotective effects, extensive controversy exists regarding the role of Ang-(1-7) in obstructive nephropathy, which is characterized by renal tubulointerstitial fibrosis and apoptosis. METHODS: To examine the effects of Ang-(1-7) in unilateral ureteral obstruction (UUO), male Sprague-Dawley rats were divided into three groups: control, UUO, and Ang-(1-7)-treated UUO rats. Ang-(1-7) was continuously infused (24 MUg/[kg.h]) using osmotic pumps. We also treated NRK-52E cells in vitro with Ang II (1 MUM) in the presence or absence of Ang-(1-7) (1 MUM), Mas receptor antagonist A779 (1 MUM), and Mas receptor siRNA (50 nM) to examine the effects of Ang-(1-7) treatment on Ang II-stimulated renal injury via Mas receptor. RESULTS: Angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R) protein expression was higher in UUO kidneys than in controls. Ang-(1-7) treatment also decreased proapoptotic protein expression in UUO kidneys. Ang-(1-7) also significantly ameliorated TUNEL positive cells in UUO kidneys. Additionally, Ang-(1-7) reduced profibrotic protein expression and decreased the increased tumor growth factor (TGF)-beta1/Smad signaling present in UUO kidneys. In NRK-52E cells, Ang II induced the expression of TGF-beta1/Smad signaling effectors and proapoptotic and fibrotic proteins, as well as cell cycle arrest, which were attenuated by Ang-(1 7) pretreatment. However, treatment with A779 and Mas receptor siRNA enhanced Ang II-induced apoptosis and fibrosis. Moreover, Ang II increased tumor necrosis factor-alpha converting enzyme (TACE) and decreased angiotensin-converting enzyme 2 (ACE2) expression in NRK-52E cells, while pretreatment with Ang-(1-7) or A779 significantly inhibited or enhanced these effects, respectively. CONCLUSION: Ang (1-7) prevents obstructive nephropathy by suppressing renal apoptosis and fibrosis, possibly by regulating TGF-beta1/Smad signaling and cell cycle arrest via suppression of AT1R expression. In addition, Ang-(1-7) increased and decreased ACE2 and TACE expression, respectively, which could potentially mediate a positive feedback mechanism via the Mas receptor. PMID- 26556708 TI - INTEGRATE: gene fusion discovery using whole genome and transcriptome data. AB - While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use. PMID- 26556709 TI - Assessment of adherence to topical corticosteroids in patients with bullous pemphigoid. PMID- 26556710 TI - Pi (Spleen)-deficiency syndrome in tumor microenvironment is the pivotal pathogenesis of colorectal cancer immune escape. AB - Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting. PMID- 26556712 TI - Abstracts of the 31st Turkish Cardiology Congress with International Participation. October 22-25, 2015, Antalya, Turkey. PMID- 26556711 TI - Temporal Patterns and Environmental Correlates of Macroinvertebrate Communities in Temporary Streams. AB - Temporary streams are characterised by short periods of seasonal or annual stream flow after which streams contract into waterholes or pools of varying hydrological connectivity and permanence. Although these streams are widespread globally, temporal variability of their ecology is understudied, and understanding the processes that structure community composition in these systems is vital for predicting and managing the consequences of anthropogenic impacts. We used multivariate and univariate approaches to investigate temporal variability in macroinvertebrate compositional data from 13 years of sampling across multiple sites from autumn and spring, in South Australia, the driest state in the driest inhabited continent in the world. We examined the potential of land-use, geographic and environmental variables to predict the temporal variability in macroinvertebrate assemblages, and also identified indicator taxa, that is, those highly correlated with the most significantly associated physical variables. Temporal trajectories of macroinvertebrate communities varied within site in both seasons and across years. A combination of land-use, geographic and environmental variables accounted for 24% of the variation in community structure in autumn and 27% in spring. In autumn, community composition among sites were more closely clustered together relative to spring suggesting that communities were more similar in autumn than in spring. In both seasons, community structure was most strongly correlated with conductivity and latitude, and community structure was more associated with cover by agriculture than urban land-use. Maintaining temporary streams will require improved catchment management aimed at sustaining seasonal flows and critical refuge habitats, while also limiting the damaging effects from increased agriculture and urban developments. PMID- 26556713 TI - Sampling and Complementarity Effects of Plant Diversity on Resource Use Increases the Invasion Resistance of Communities. AB - BACKGROUND: Although plant diversity is postulated to resist invasion, studies have not provided consistent results, most of which were ascribed to the influences of other covariate environmental factors. METHODOLOGY/PRINCIPAL FINDINGS: To explore the mechanisms by which plant diversity influences community invasibility, an experiment was conducted involving grassland sites varying in their species richness (one, two, four, eight, and sixteen species). Light interception efficiency and soil resources (total N, total P, and water content) were measured. The number of species, biomass, and the number of seedlings of the invading species decreased significantly with species richness. The presence of Patrinia scabiosaefolia Fisch. ex Trev. and Mosla dianthera (Buch.-Ham. ex Roxburgh) Maxim. significantly increased the resistance of the communities to invasion. A structural equation model showed that the richness of planted species had no direct and significant effect on invasion. Light interception efficiency had a negative effect on the invasion whereas soil water content had a positive effect. In monocultures, Antenoron filiforme (Thunb.) Rob. et Vaut. showed the highest light interception efficiency and P. scabiosaefolia recorded the lowest soil water content. With increased planted-species richness, a greater percentage of pots showed light use efficiency higher than that of A. filiforme and a lower soil water content than that in P. scabiosaefolia. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that plant diversity confers resistance to invasion, which is mainly ascribed to the sampling effect of particular species and the complementarity effect among species on resources use. PMID- 26556714 TI - Age related differences in mechanical demands imposed on the lower back by manual material handling tasks. AB - The prevalence of low back pain (LBP) increases with age, yet the underlying mechanism(s) responsible for this remains unclear. To explore the role of biomechanical factors, we investigated age-related differences in lower-back biomechanics during sagittally-symmetric simulated manual material handling tasks. For each task, trunk kinematics and mechanical demand on the lower back were examined, from among 60 participants within five equal-sized and gender balanced age groups spanning from 20 to 70 years old. The tasks involved lowering a 4.5 kg load from an upright standing posture to both knee height and a fixed height and then lifting the load back to the initial upright posture. During these tasks, segmental body kinematics and ground reaction forces were collected using wireless inertial measurement units and a force platform. Overall, older participants completed the tasks with larger pelvic rotation and smaller lumbar flexion. Such adopted trunk kinematics resulted in larger peak shearing demand at the lower back in older vs. younger participants. These results suggest that older individuals may be at a higher risk for developing lower back pain when completing similar manual material handling tasks, consistent with epidemiological evidence for higher risks of occupational low back pain among this cohort. PMID- 26556715 TI - Quantification of angiogenic sprouting under different growth factors in a microfluidic platform. AB - Angiogenesis, as example of collective migration of endothelial cells (ECs), is the main dynamic process that culminates in sprout formation from existing vessels. After tissue injury, the vascularity is interrupted, triggering the regeneration process and the release of different growth factors (GFs). The main aim of this work is to quantify the effect of specific GFs during the initial stage of sprout formation, namely: VEGF, PDGF-BB, TGFbeta and BMP-2, all of them involved in regenerative processes. For this purpose, we designed a novel algorithm implemented in Matlab to quantify the advance of the EC monolayer over time and the sprout structure in 3D. Our results show that VEGF is the main regulatory GF on angiogenesis processes, producing longer sprouts with higher frequency. However, the chemoattractant effect of VEGF depends on its concentration and its spatiotemporal location, having a critical impact on the sprout time evolution. PDGF-BB (namely as PDGF) has a global negative effect on both the number and length of sprouts. TGFbeta enhances sprout length at earlier times, although its effect gradually disappears over time. Finally, BMP-2 produces, overall, less number and shorter sprouts, but was the only GF with a positive evolution at longer times, producing fewer but longer sprouts. PMID- 26556716 TI - Neck incision planning for total laryngectomy: A finite element analysis. AB - Post-operative complications can be attributed to technical aspects of surgery, yet no studies have investigated the mechanics behind commonly used incisions for total laryngopharyngectomies (TLP). This procedure, seen in head and neck cancer patients, necessitates free tissue transfer to construct a neo-pharynx, creating an inherently greater risk of complications. We sought to investigate the impact of neck incision location on these post-operative complications for TLP using finite element analysis (FEA). A nonlinear hyperelastic 2-D finite element model was used to evaluate the stress and strain along the incision line of two separate neck incision models commonly used for TLP: low-neck apron (LNA) incisions that incorporate the patient's tracheostoma and mid-neck apron (MNA) incisions that do not communicate with the tracheostoma. A constant displacement was applied to the incision to simulate normal neck extension experienced during the post-operative phase. Each neck incision was also modeled at varying strain energy densities to simulate various stages of wound healing. For a constant displacement of 40mm, the principal von Mises stress of the LNA incision varied between 5.87 and 6.41MPa, depending on the hyperelastic properties of the healing incision. This stress was concentrated at the junction of the incision and the fixed tracheostomal edge. The MNA model demonstrated a principal von Mises stress that varied between 0.558 and 0.711MPa and was concentrated along the midline of the neck incision. MNA incisions for TL patients result in principal von Mises stresses which are up to 11 times lower than those seen in LNA incisions. These results coincided with clinical observations from a concurrent study that showed a decrease in rate of wound dehiscence for patients undergoing TLP with an MNA incision. PMID- 26556717 TI - MRI analyses show that kinesio taping affects much more than just the targeted superficial tissues and causes heterogeneous deformations within the whole limb. AB - Kinesio taping (KT) is widely used in the treatment of sports injuries and various neuro-musculoskeletal disorders. However, it is considered as selectively effective on targeted tissues and its mechanical effects have not been quantified objectively. Ascribed to continuity of muscular and connective tissues, mechanical loading imposed can have widespread heterogeneous effects. The aim was to characterize the mechanical effects of KT objectively and to test the hypotheses that KT causes acutely, local deformations not necessarily (I) in agreement with tape adhering direction and (II) limited to the directly targeted tissues. High-resolution 3D magnetic resonance image sets were acquired in healthy human subjects (n=5) prior to and acutely after KT application over the skin along m. tibialis anterior (TA). Hip, knee and ankle angles were kept constant. Demons image registration algorithm was used to calculate local tissue deformations within the lower leg, in vivo. Mean peak tissue strains were significantly higher than strain artifacts. Only KT-to-TA region in part shows local deformations in agreement with tape adhering direction whereas, superficial skin, the rest of KT-to-TA and TA regions show deformations (up to 51.5% length change) in other directions. Non-targeted tissues also show sizable heterogeneous deformations, but in smaller amplitudes. Inter-subject variability is notable. Magnetic resonance imaging analyses allow for a detailed assessment of local tissue deformation occurring acutely after KT application. The findings confirm our hypotheses and characterize how KT affects the underlying tissues, both immediately targeted and distant. This allows revealing mechanisms that can affect clinical outcomes of KT objectively. PMID- 26556719 TI - Infection levels and seasonality of monogeneans in the largemouth bass Micropterus salmoides (Perciformes: Centrarchidae) from Nuevo Leon, Mexico. AB - Largemouth bass, Micropterus salmoides, is a native fish species with special importance for sport fishing competitions in Nuevo Leon, Mexico. However, no study has investigated the parasitic fauna of M. salmoides, and no reports are available on monogenean parasites in this fish species. Therefore, we described the monogenean parasites of M. salmoides and the effects of season and fish condition factor in five reservoirs: La Boca (LB), El Cuchillo-Solidaridad (CS), Sombreretillo (S), Laguna Salinillas (LS) and Cerro Prieto (CP). The monogeneans infecting M. salmoides were Clavunculus unguis and Acolpenteron ureteroecetes (collected in all localities), as well as Syncleithrium fusiformis, Haplocleidus furcatus, Clavunculus bifurcatus and Urocleidus principalis (CS). Clavunculus unguis had the highest prevalence in fish from all reservoirs. The abundance of monogeneans was generally greater in late spring to autumn than in winter. Although season was not correlated with abundance (r s = 0.0934, P < 0.0154), the months of highest temperature (from May to September) were positively correlated with parasite abundance. A significant association was observed between fish condition factor and the presence of monogeneans (P < 0.05), except for A. ureteroecetes. Our findings include five new geographic records for C. unguis, S. fusiformis, H. furcatus and C. bifurcatus. PMID- 26556718 TI - Cyclooxygenase-2, a Potential Therapeutic Target, Is Regulated by miR-101 in Esophageal Squamous Cell Carcinoma. AB - BACKGROUND & AIMS: Cyclooxygenase-2 (COX-2) is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC). There are no reports on whether microRNAs (miRNAs) regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8), transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA). The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC. RESULTS: Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001), as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001). Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001). The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR 101. CONCLUSIONS: Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC. PMID- 26556720 TI - Correction: Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry. PMID- 26556722 TI - Obesity and the Relative Risk of Knee Replacement Surgery in Patients With Knee Osteoarthritis: A Prospective Cohort Study. AB - OBJECTIVE: It is unclear what impact obesity has on the progression of knee osteoarthritis (OA) from diagnosis to knee replacement surgery. This study was undertaken to examine the relative risk of knee replacement surgery in overweight and obese patients who were newly diagnosed as having knee OA in a community setting. METHODS: Subjects were selected from the Information System for Development of Primary Care Research database, which compiles comprehensive clinical information collected by health care professionals for >5.5 million people in Catalonia, Spain (80% of the population). Patients newly diagnosed as having knee OA in primary care between 2006 and 2011 were included. Knee replacement was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification codes from linked hospital admissions data. Multivariable Cox regression models were fitted for knee replacement according to body mass index (BMI), and were adjusted for relevant confounders. Population proportional attributable risk was calculated. RESULTS: A total of 105,189 participants were followed up for a median of 2.6 years (interquartile range 1.3 4.2). Of these patients, 7,512 (7.1%) underwent knee replacement. Adjusted hazard ratios and 95% confidence intervals (95% CIs) for knee replacement for the World Health Organization BMI categories were 1.41 (95% CI 1.27-1.57) for overweight, 1.97 (95% CI 1.78-2.18) for obese I, 2.39 (95% CI 2.15-2.67) for obese II, and 2.67 (95% CI 2.34-3.04) for obese III compared to normal weight. The effect of BMI on risk of knee replacement was stronger among younger participants. The population attributable risk of obesity for knee OA-related knee replacement was 31.0%. CONCLUSION: Overweight and obese patients are at >40% and 100% increased risk of knee replacement surgery, respectively, compared to patients with normal weight. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for knee replacement surgery by 31% among patients with knee OA. PMID- 26556721 TI - Schisandrin B Ameliorates ICV-Infused Amyloid beta Induced Oxidative Stress and Neuronal Dysfunction through Inhibiting RAGE/NF-kappaB/MAPK and Up-Regulating HSP/Beclin Expression. AB - Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). Our previous studies have demonstrated that schisandrin B (Sch B), an antioxidant lignan from Schisandra chinensis, could protect mouse brain against scopolamine- and cisplatin-induced neuronal dysfunction. In the present study, we examined the protective effect of Sch B against intracerebroventricular (ICV)-infused Abeta-induced neuronal dysfunction in rat cortex and explored the potential mechanism of its action. Our results showed that 26 days co-administration of Sch B significantly improved the behavioral performance of Abeta (1-40)-infused rats in step-through test. At the same time, Sch B attenuated Abeta-induced increases in oxidative and nitrosative stresses, inflammatory markers such as inducible nitric oxide syntheses, cyclooxygenase-2, interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha, and DNA damage. Several proteins such as receptor for advanced glycation end products (RAGE), nuclear factor-kappaB, mitogen-activated protein kinases, and apoptosis markers were over expressed in Abeta-infused rats but were significantly inhibited by Sch B treatment. Furthermore, Sch B negatively modulated the Abeta level with simultaneous up-regulation of HSP70 and beclin, autophagy markers in Abeta-infused rats. The aforementioned effects of Sch B suggest its protective role against Abeta-induced neurotoxicity through intervention in the negative cycle of RAGE-mediated Abeta accumulation during AD patho-physiology. PMID- 26556723 TI - Targeted drug delivery using genetically engineered diatom biosilica. AB - The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites. PMID- 26556724 TI - Interaction of ApoA-IV with NR4A1 and NR1D1 Represses G6Pase and PEPCK Transcription: Nuclear Receptor-Mediated Downregulation of Hepatic Gluconeogenesis in Mice and a Human Hepatocyte Cell Line. AB - We have previously shown that the nuclear receptor, NR1D1, is a cofactor in ApoA IV-mediated downregulation of gluconeogenesis. Nuclear receptor, NR4A1, is involved in the transcriptional regulation of various genes involved in inflammation, apoptosis, and glucose metabolism. We investigated whether NR4A1 influences the effect of ApoA-IV on hepatic glucose metabolism. Our in situ proximity ligation assays and coimmunoprecipitation experiments indicated that ApoA-IV colocalized with NR4A1 in human liver (HepG2) and kidney (HEK-293) cell lines. The chromatin immunoprecipitation experiments and luciferase reporter assays indicated that the ApoA-IV and NR4A1 colocalized at the RORalpha response element of the human G6Pase promoter, reducing its transcriptional activity. Our RNA interference experiments showed that knocking down the expression of NR4A1 in primary mouse hepatocytes treated with ApoA-IV increased the expression of NR1D1, G6Pase, and PEPCK, and that knocking down NR1D1 expression increased the level of NR4A1. We also found that ApoA-IV induced the expression of endogenous NR4A1 in both cultured primary mouse hepatocytes and in the mouse liver, and decreased glucose production in primary mouse hepatocytes. Our findings showed that ApoA-IV colocalizes with NR4A1, which suppresses G6Pase and PEPCK gene expression at the transcriptional level, reducing hepatic glucose output and lowering blood glucose. The ApoA-IV-induced increase in NR4A1 expression in hepatocytes mediates further repression of gluconeogenesis. Our findings suggest that NR1D1 and NR4A1 serve similar or complementary functions in the ApoA-IV-mediated regulation of gluconeogenesis. PMID- 26556725 TI - Prospective function of FtsZ proteins in the secondary plastid of chlorarachniophyte algae. AB - BACKGROUND: Division of double-membraned plastids (primary plastids) is performed by constriction of a ring-like division complex consisting of multiple plastid division proteins. Consistent with the endosymbiotic origin of primary plastids, some of the plastid division proteins are descended from cyanobacterial cell division machinery, and the others are of host origin. In several algal lineages, complex plastids, the "secondary plastids", have been acquired by the endosymbiotic uptake of primary plastid-bearing algae, and are surrounded by three or four membranes. Although homologous genes for primary plastid division proteins have been found in genome sequences of secondary plastid-bearing organisms, little is known about the function of these proteins or the mechanism of secondary plastid division. RESULTS: To gain insight into the mechanism of secondary plastid division, we characterized two plastid division proteins, FtsZD 1 and FtsZD-2, in chlorarachniophyte algae. FtsZ homologs were encoded by the nuclear genomes and carried an N-terminal plastid targeting signal. Immunoelectron microscopy revealed that both FtsZD-1 and FtsZD-2 formed a ring like structure at the midpoint of bilobate plastids with a projecting pyrenoid in Bigelowiella natans. The ring was always associated with a shallow plate-like invagination of the two innermost plastid membranes. Furthermore, gene expression analysis confirmed that transcripts of ftsZD genes were periodically increased soon after cell division during the B. natans cell cycle, which is not consistent with the timing of plastid division. CONCLUSIONS: Our findings suggest that chlorarachniophyte FtsZD proteins are involved in partial constriction of the inner pair of plastid membranes, but not in the whole process of plastid division. It is uncertain how the outer pair of plastid membranes is constricted, and as-yet-unknown mechanism is required for the secondary plastid division in chlorarachniophytes. PMID- 26556726 TI - The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. AB - Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases. Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved. We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP(+) toxicity in PC12 cells. CBD increased cell viability, differentiation, and the expression of axonal (GAP-43) and synaptic (synaptophysin and synapsin I) proteins. Its neuritogenic effect was not dependent or additive to NGF, but it was inhibited by K252a (trkA inhibitor). CBD did not increase the expression of NGF, but protected against its decrease induced by MPP(+), probably by an indirect mechanism. We also evaluated the neuritogenesis in SH-SY5Y cells, which do not express trkA receptors. CBD did not induce neuritogenesis in this cellular model, which supports the involvement of trkA receptors. This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD. Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP(+), a neurotoxin relevant to Parkinson's disease. PMID- 26556727 TI - Comparison of Intelligibility Measures for Adults With Parkinson's Disease, Adults With Multiple Sclerosis, and Healthy Controls. AB - PURPOSE: This study obtained judgments of sentence intelligibility using orthographic transcription for comparison with previously reported intelligibility judgments obtained using a visual analog scale (VAS) for individuals with Parkinson's disease and multiple sclerosis and healthy controls (K. Tjaden, J. E. Sussman, & G. E. Wilding, 2014). METHOD: Speakers read Harvard sentences in habitual, clear, loud, and slow conditions. Sentence stimuli were equated for peak intensity and mixed with multitalker babble. A total of 50 listeners orthographically transcribed sentences. Procedures were identical to those for a VAS reported in Tjaden, Sussman, and Wilding (2014). RESULTS: The percent correct scores from transcription were significantly higher in magnitude than the VAS scores. Multivariate linear modeling indicated that the pattern of findings for transcription and VAS was virtually the same with respect to differences among groups and speaking conditions. Correlation analyses further indicated a moderately strong, positive relationship between the two metrics. The majority of these correlations were significant. Last, intrajudge and interjudge listener reliability metrics for the two intelligibility tasks were comparable. CONCLUSION: Results suggest that there may be instances when the less time consuming VAS task may be a viable substitute for an orthographic transcription task when documenting intelligibility in mild dysarthria. PMID- 26556728 TI - Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol? AB - BACKGROUND: Shared neurophysiologic features between sleep and anesthetic-induced hypnosis indicate a potential overlap in neuronal circuitry underlying both states. Previous studies in rodents indicate that preexisting sleep debt discharges under propofol anesthesia. The authors explored the hypothesis that propofol anesthesia also dispels sleep pressure in the fruit fly. To the authors' knowledge, this constitutes the first time propofol has been tested in the genetically tractable model, Drosophila melanogaster. METHODS: Daily sleep was measured in Drosophila by using a standard locomotor activity assay. Propofol was administered by transferring flies onto food containing various doses of propofol or equivalent concentrations of vehicle. High-performance liquid chromatography was used to measure the tissue concentrations of ingested propofol. To determine whether propofol anesthesia substitutes for natural sleep, the flies were subjected to 10-h sleep deprivation (SD), followed by 6-h propofol exposure, and monitored for subsequent sleep. RESULTS: Oral propofol treatment causes anesthesia in flies as indicated by a dose-dependent reduction in locomotor activity (n = 11 to 41 flies from each group) and increased arousal threshold (n = 79 to 137). Recovery sleep in flies fed propofol after SD was delayed until after flies had emerged from anesthesia (n = 30 to 48). SD was also associated with a significant increase in mortality in propofol-fed flies (n = 44 to 46). CONCLUSIONS: Together, these data indicate that fruit flies are effectively anesthetized by ingestion of propofol and suggest that homologous molecular and neuronal targets of propofol are conserved in Drosophila. However, behavioral measurements indicate that propofol anesthesia does not satisfy the homeostatic need for sleep and may compromise the restorative properties of sleep. PMID- 26556729 TI - Patient-controlled Analgesia with Target-controlled Infusion of Hydromorphone in Postoperative Pain Therapy. AB - BACKGROUND: Patient-controlled analgesia (PCA) is a common method for postoperative pain therapy, but it is characterized by large variation of plasma concentrations. PCA with target-controlled infusion (TCI-PCA) may be an alternative. In a previous analysis, the authors developed a pharmacokinetic model for hydromorphone. In this secondary analysis, the authors investigated the feasibility and efficacy of TCI-PCA for postoperative pain therapy with hydromorphone. METHODS: Fifty adult patients undergoing cardiac surgery were enrolled in this study. Postoperatively, hydromorphone was applied intravenously during three sequential periods: (1) as TCI with plasma target concentrations of 1 to 2 ng/ml until extubation; (2) as TCI-PCA with plasma target concentrations between 0.8 and 10 ng/ml during the following 6 to 8 h; and (3) thereafter as PCA with a bolus dose of 0.2 mg until the next morning. During TCI-PCA, pain was regularly assessed using the 11-point numerical rating scale (NRS). A pharmacokinetic/pharmacodynamic model was developed using ordinal logistic regression based on measured plasma concentrations. RESULTS: Data of 43 patients aged 40 to 81 yr were analyzed. The hydromorphone dose during TCI-PCA was 0.26 mg/h (0.07 to 0.93 mg/h). The maximum plasma target concentration during TCI-PCA was 2.3 ng/ml (0.9 to 7.0 ng/ml). The NRS score under deep inspiration was less than 5 in 83% of the ratings. Nausea was present in 30%, vomiting in 9%, and respiratory insufficiency in 5% of the patients. The EC50 of hydromorphone for NRS of 4 or less was 4.1 ng/ml (0.6 to 12.8 ng/ml). CONCLUSION: TCI-PCA with hydromorphone offered satisfactory postoperative pain therapy with moderate side effects. PMID- 26556730 TI - Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. AB - BACKGROUND: Surgical resection remains the best option for long-term survival in many solid tumors. Surgery can, however, lead to tumor cell release into the circulation. Data have suggested differential effects of anesthetic agents on cancer cell growth. This retrospective analysis investigated the association of anesthetic technique with long-term survival in patients presenting for elective surgery in a comprehensive cancer center over 3 yr. METHODS: All patients undergoing elective surgery between June 2010 and May 2013 were included. Patients were grouped according to whether they had received volatile inhalational (INHA) or total IV anesthesia (TIVA). After excluding those who received both forms of anesthesia during the study period, Kaplan-Meier survival curves were constructed from the date of surgery to death. After propensity matching, univariate and multivariable regression models were used to compare hazard ratios for death. RESULTS: A total of 11,395 anesthetics using INHA or TIVA were delivered in the study period. After exclusions, 3,316 patients (796 deaths, 24%) remained in the INHA group and 3,714 (504 deaths, 13.5%) in the TIVA group. After propensity matching, 2,607 patients remained in each group (597 deaths, 22.8%, in INHA group vs. 407, 15.6%, in TIVA group). Volatile inhalational anesthesia was associated with a hazard ratio of 1.59 (1.30 to 1.95) for death on univariate analysis and 1.46 (1.29 to 1.66) after multivariable analysis of known confounders in the matched group. CONCLUSIONS: This retrospective analysis demonstrates an association between type of anesthetic delivered and survival. This analysis alongside biological plausibility should lead to urgent prospective work exploring the effect of anesthetic technique on survival. PMID- 26556732 TI - Exercise for the skeleton in postmenopausal women: fundamental rules of mechanical strain-related stimulus. PMID- 26556731 TI - Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells. AB - Natural killer (NK) cells play a vital antitumor role as part of the innate immune system. Efficacy of adoptive transfer of NK cells depends on their ability to recognize and target tumors. We investigated whether low dose focused ultrasound with microbubbles (ldbFUS) could facilitate the targeting and accumulation of NK cells in a mouse xenograft of human colorectal adenocarcinoma (carcinoembryonic antigen (CEA)-expressing LS-174T implanted in NOD.Cg PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice) in the presence of an anti-CEA immunocytokine (ICK), hT84.66/M5A-IL-2 (M5A-IL-2). Human NK cells were labeled with an FDA-approved ultra-small superparamagnetic iron oxide particle, ferumoxytol. Simultaneous with the intravenous injection of microbubbles, focused ultrasound was applied to the tumor. In vivo longitudinal magnetic resonance imaging (MRI) identified enhanced accumulation of NK cells in the ensonified tumor, which was validated by endpoint histology. Significant accumulation of NK cells was observed up to 24 hrs at the tumor site when ensonified with 0.50 MPa peak acoustic pressure ldbFUS, whereas tumors treated with at 0.25 MPa showed no detectable NK cell accumulation. These clinically translatable results show that ldbFUS of the tumor mass can potentiate tumor homing of NK cells that can be evaluated non-invasively using MRI. PMID- 26556733 TI - Effects of zoledronic acid on bone fusion in osteoporotic patients after lumbar fusion. AB - Treatment with zoledronic acid in osteoporotic patients with spinal fusion shortens the duration of time to fusion, improves the fusion rate, prevents the subsequent adjacent vertebral compression fractures, improves the clinical outcomes, and prevents immobilization-induced bone loss in the hip. INTRODUCTION: The objective of the study was to explore the effects of zoledronic acid on the healing process in osteoporotic patients following spinal fusion in a randomized, placebo-controlled, and triple-blinded study. METHODS: Seventy-nine osteoporotic patients with single-level degenerative spondylolisthesis were randomly assigned to receive either zoledronic acid infusion (zoledronic acid group) or saline infusion (controls) after spinal fusion. Functional radiography and CT scans were used to evaluate fusion status. Bone formation was graded into three categories: Grade A (bridging bone bonding with adjacent vertebral bodies), Grade B (bridging bone bonding with either superior or inferior vertebral body), or Grade C (incomplete bony bridging). A solid fusion was defined as less than 5 degrees of angular motion with Grade A or B bone formation. Adjacent vertebral compression fractures (VCF) were assessed on MRI at 12 months after surgery. Serum level of carboxy terminal cross-linked telopeptide of type I collagen (beta-CTX) and amino terminal propeptide of type I procollagen (PINP) was measured. Bone mineral density (BMD) was measured by DXA. Oswestry Disability Index (ODI) was used to assess the clinical outcomes. RESULTS: Grade A or B bridging bone was more frequently observed in zoledronic acid group at 3, 6, and 9 months post-operation compared to the control group (p < 0.05). At 12 -months post-operation, bridging bone and solid fusion were not significantly different between groups. No patients in zoledronic acid group showed aVCF, whereas six patients (17 %) in the control group did (p < 0.05). Both beta-CTX and PINP were suppressed in zoledronic acid group. BMD at the femoral neck decreased rapidly and did not return to the preoperative level in the controls at 3 (-1.4 %), 6 (-2.5 %), and 12 (-0.8 %) months after surgery. Zoledronic acid prevented this immobilization induced bone loss and increased BMD. ODI showed the improved clinical outcomes compared with controls at 9 and 12 months post-surgery. CONCLUSION: Treatment with zoledronic acid in osteoporotic patients with spinal fusion shortens the time to fusion, improves the fusion rate, prevents subsequent aVCFs, and improves clinical outcomes. PMID- 26556734 TI - Accuracy of densitometric vertebral fracture assessment when performed by DXA technicians--a cross-sectional, multiobserver study. AB - Six dual-energy X-ray absorptiometry (DXA) technicians reviewed lateral images of the spine for deformed vertebrae. The images were acquired with a DXA scanner in 235 patients referred for osteoporosis assessment. The outcome was compared to findings on spinal radiographs assessed by two radiologists. Three DXA technicians performed acceptable or better in identifying patients with fractured vertebrae. INTRODUCTION: This is the first study to evaluate the accuracy of vertebral fracture assessment (VFA) when used by DXA technicians as a triage test to select patients with deformed vertebrae for spinal radiographs. METHODS: Lateral single-energy scans and radiographs of the thoracolumbar spine (T4-L4) were acquired in 235 patients aged 65 years or more referred for osteoporosis assessment. Six DXA technicians evaluated lateral scans using dedicated software. The DXA technicians were trained to identify deformed vertebrae, but they did not assess the aetiology of deformity. Two radiologists evaluated the radiographs and their consensus evaluation served as the reference test for vertebral fracture. The main outcome was sensitivity and specificity of the DXA technicians' identification of patients with one or more grade II-III deformities according to Genant's classification. RESULTS: The proportion of patients with one or more grade II-III vertebral fractures was 0.35. Sensitivity ranged from 0.61 to 0.83 and specificity ranged from 0.78 to 0.95 across the DXA technicians. In patients with grade II-III deformities on VFA, the mean probability of one or more grade II-III fractures was 0.74 (range 0.66-0.86). Conversely, in patients without such deformities, the mean probability of grade II-III fractures was 0.14 (range 0.10 0.18). Accuracy was lower for grade I-III deformities for all the DXA technicians. CONCLUSION: Three of six DXA technicians achieved acceptable or better accuracy when using VFA to triage patients with grade II-III vertebral deformities for spinal radiographs. Heterogeneity between DXA technicians appears to be due to differences in subjective thresholds. VFA triage by DXA technicians to identify patients with grade II-III fractures is feasible. PMID- 26556735 TI - Calcium, proton pump inhibitors, and fracture risk. PMID- 26556736 TI - A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates. AB - In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION: This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post menopausal women with osteoporosis. METHODS: This randomized, active and placebo controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for >=12 months preceding the trial and any oral bisphosphonate for >=3 of the preceding 4 years and had spine or hip BMD T-scores <=-2.5 or <= 1.5 with >=1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. RESULTS: Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442. CONCLUSION: Switching from ALN to MK 5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis. PMID- 26556737 TI - Patients with prior vertebral or hip fractures treated with teriparatide in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study. AB - SUMMARY: In patients in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study with and without a prior vertebral or hip fracture, the incidence of nonvertebral fractures was lower with >6 months of teriparatide treatment than during the first 6 months. INTRODUCTION: Clinical evidence on the effect of teriparatide in patients with prior fracture is limited. In the DANCE observational study, the incidence of nonvertebral fragility fractures (NVFX) decreased significantly in patients receiving teriparatide for >6 months (6-24 months) versus >0 to <=6 months (reference period). METHODS: We performed a post hoc analysis to assess the effect of teriparatide 20 MUg/day in patients who entered DANCE with prior vertebral or hip fractures. The incidence of patients experiencing a NVFX for four 6-month intervals during and after treatment was compared with the reference period. RESULTS: Overall, 4085 patients received >=1 dose of teriparatide. Of 3720 with sufficient data for efficacy analysis, 692 had prior vertebral fracture, including 179 with previous kyphoplasty/vertebroplasty; 290 had prior hip fracture. These patients were older, and those with prior vertebral fractures had more comorbid conditions at baseline than those without prior vertebral fractures. The incidence of patients experiencing NVFX declined over time in all patient groups. The fracture incidence rate declined 49 and 46%, respectively, in patients with and without prior vertebral fracture and was 63 and 46% lower in patients with previous kyphoplasty/vertebroplasty and without prior vertebral fracture. NVFX declined 43 and 48% in patients with and without prior hip fracture. The reduced incidence over time was consistent in the subgroups (all interaction p values >0.05). Patients with prior fracture were more likely to experience serious adverse events. CONCLUSION: The incidence of NVFX decreased over time in patients receiving teriparatide in DANCE regardless of prior fracture status. PMID- 26556738 TI - An exploration of barriers and facilitators to older adults' participation in higher impact physical activity and bone health: a qualitative study. AB - SUMMARY: This qualitative study explored the acceptability of high-impact physical activity for increasing bone strength in later life. Thematic analysis established the barriers and facilitators to this physical activity. They prioritised joint over skeletal health, of which they had little concept. Interventions need to clearly communicate the rationale and benefits. INTRODUCTION: The aim of this study was to explore the acceptability of doing high-impact physical activity in later life. METHODS: This qualitative study was embedded within a large-scale observational study and was designed to address specific objectives and feed into a subsequent intervention. Five focus groups with physically active men and women (over 50 years) were used to develop an interview topic guide to explore the acceptability of high-impact physical activity in older men and women (over 65 years) in South West England. A total of 28 semi-structured interviews with 31 participants were then conducted and transcripts analysed thematically. RESULTS: Three main barriers emerged: conceptualising bone, damage to joints and falling/safety concerns. Two main facilitators were also identified: the need to understand clear tangible benefits and incorporation of activity into everyday habits. Older adults were interested how high-impact physical activity would help to maintain their mobility, independence or social relationships. Some participants wanted tangible feedback from accelerometers, health care professionals and/or bone scans in order to develop a more intimate knowledge of their bone health. CONCLUSIONS: Interventions incorporating high-impact physical activity for older adults need to communicate how this activity can impact more broadly on health and lives; that physical activity will be safe, beneficial and not damaging to their joints will need to be clearly conveyed. Ways in which high-impact physical activity can be habitualised into everyday activities, be fun and interactive may help facilitate longer term adoption. PMID- 26556739 TI - Glucocorticoids impair bone formation of bone marrow stromal stem cells by reciprocally regulating microRNA-34a-5p. AB - The inhibitory effects of glucocorticoids (GCs) on bone marrow stromal stem cell (BMSC) proliferation and osteoblastic differentiation are an important pathway through which GCs decrease bone formation. We found that microRNA-34a-5p was a critical player in dexamethasone (Dex)-inhibited BMSC proliferation and osteogenic differentiation. MicroRNA-34a-5p might be used as a therapeutic target for GC-impaired bone formation. INTRODUCTION: The inhibitory effects of glucocorticoids (GCs) on bone marrow stromal stem cell (BMSC) proliferation and osteoblastic differentiation are an important pathway through which GCs decrease bone formation. The mechanisms of this process are still not completely understood. Recent studies implicated an important role of microRNAs in GC mediated responses in various cellular processes, including cell proliferation and differentiation. Therefore, we hypothesized that these regulatory molecules might be implicated in the process of GC-decreased BMSC proliferation and osteoblastic differentiation. METHODS: Western blot, quantitative real-time PCR, and cell proliferation and osteoblastic differentiation assays were employed to investigate the role of microRNAs in GC-inhibited BMSC proliferation and osteoblastic differentiation. RESULTS: We found that microRNA-34a-5p was reciprocally regulated by Dex during the process of BMSC proliferation and osteoblastic differentiation. Furthermore, we confirmed that microRNA-34a-5p was a critical player in Dex-inhibited BMSC proliferation and osteogenic differentiation. Mechanistic studies showed that Dex inhibited BMSC proliferation by microRNA-34a-5p targeting cell cycle factors, including CDK4, CDK6, and Cyclin D1. Furthermore, downregulation of microRNA-34a-5p by Dex leads to Notch signaling activation, resulting in inhibition of BMSC osteogenic differentiation. CONCLUSIONS: These results showed that microRNA-34a-5p, a crucial regulator for BMSC proliferation and osteogenic differentiation, might be used as a therapeutic target for GC-impaired bone formation. PMID- 26556740 TI - Bilateral distal fibula fractures in a woman on long-term bisphosphonate therapy. AB - We report the case of a 53-year-old female, treated by bisphosphonate for 12 years, who presented atraumatic fractures of both fibulas. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. The distal fibula should be considered as a potential site for stress fractures in bisphosphonate users. Bisphosphonates are the most widely used drugs in the treatment of osteoporosis. During the last decade, the occurrence of atypical fractures, mostly subtrochanteric and diaphyseal femoral fractures, has been acknowledged in patients with long-term use of bisphosphonates. We report the case of a 53-year-old female on alendronate therapy for the past 12 years who presented with a few months history of atraumatic right, and subsequently left, lateral ankle pain. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. She had been treated conservatively with walking boots and her treatment with bisphosphonate had been stopped 5 months prior to the fractures. Callus was progressively seen on serial follow-up X-rays, and both fractures healed completely within a reasonable period of 1 year. Investigations did not reveal any secondary causes of osteoporosis or metabolic bone disorders. To our knowledge, this is the first reported case of bilateral distal fibula fractures in a patient on long-term bisphosphonate therapy. PMID- 26556741 TI - New method for point-of-care osteoporosis screening and diagnostics. AB - SUMMARY: Due to the lack of diagnostics in primary health care, over 75% of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest applicability of ultrasound method for osteoporosis diagnostics at primary health care. INTRODUCTION: We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a new ultrasound (US) method is proposed for osteoporosis diagnostics. METHODS: A total of 572 Caucasian women (age 20 to 91 years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMD(neck)) and total hip (BMD(total)) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50 years of age (n = 445, age = 68.8 +/- 8.5 years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants. RESULTS: Osteoporosis was diagnosed in individuals with a T-score -2.5 or less in the total hip or femoral neck (n = 75). By using the ISCD approach for the DI, only 28.7% of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16% and the same treatment decisions would be reached at 85.4% sensitivity and 78.5% specificity levels. CONCLUSIONS: The present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies. PMID- 26556743 TI - Pesticide fate modeling in soils with the crop model STICS: Feasibility for assessment of agricultural practices. AB - Numerous pesticide fate models are available, but few of them are able to take into account specific agricultural practices, such as catch crop, mixing crops or tillage in their predictions. In order to better integrate crop management and crop growth in the simulation of diffuse agricultural pollutions, and to manage both pesticide and nitrogen pollution, a pesticide fate module was implemented in the crop model STICS. The objectives of the study were: (i) to implement a pesticide fate module in the crop model STICS; (ii) to evaluate the model performance using experimental data from three sites with different pedoclimatic contexts, one in The Netherlands and two in northern France; (iii) to compare the simulations with several pesticide fate models; and (iv) to test the impact of specific agricultural practices on the transfer of the dissolved fraction of pesticides. The evaluations were carried out with three herbicides: bentazone, isoproturon, and atrazine. The strategy applied in this study relies on a noncalibration approach and sensitivity test to assess the operating limits of the model. To this end, the evaluation was performed with default values found in the literature and completed by sensitivity tests. The extended version of the STICS named STICS-Pest, shows similar results with other pesticide fate models widely used in the literature. Moreover, STICS-Pest was able to estimate realistic crop growth and catch crop dynamic, which thus illustrate agricultural practices leading to a reduction of nitrate and a change in pesticide leaching. The dynamic plot-scale model, STICS-Pest is able to simulate nitrogen and pesticide fluxes, when the hydrologic context is in the validity range of the reservoir (or capacity) model. According to these initial results, the model may be a relevant tool for studying the effect of long-term agricultural practices on pesticide residue dynamics in soil and the associated diffuse pollution transfer. PMID- 26556744 TI - Screening of native plant species for phytoremediation potential at a Hg contaminated mining site. AB - Artisanal and small-scale gold mining (ASGM) is the largest sector of demand for mercury (Hg), and therefore, one of the major sources of Hg pollution in the environment. This study was conducted in the Alacran gold-mining site, one of the most important ASGM sites in Colombia, to identify native plant species growing in Hg-contaminated soils used for agricultural purposes, and to assess their potential as phytoremediation systems. Twenty-four native plant species were identified and analysed for total Hg (THg) in different tissues (roots, stems, and leaves) and in underlying soils. Accumulation factors (AF) in the shoots, translocation (TF) from roots to shoots, and bioconcentration (BCF) from soil-to roots were determined. Different tissues from all plant species were classified in the order of decreasing accumulation of Hg as follows: roots > leaves > stems. THg concentrations in soil ranged from 230 to 6320 ng g(-1). TF values varied from 0.33 to 1.73, with high values in the lower Hg-contaminated soils. No correlation was found between soils with low concentrations of Hg and plant leaves, indicating that TF is not a very accurate indicator, since most of the Hg input to leaves at ASGM sites comes from the atmosphere. On the other hand, the BCF ranged from 0.28 to 0.99, with Jatropha curcas showing the highest value. Despite their low biomass production, several herbs and sub-shrubs are suitable for phytoremediation application in the field, due to their fast growth and high AF values in large and easily harvestable plant parts. Among these species, herbs such as Piper marginathum and Stecherus bifidus, and the sub-shrubs J. curcas and Capsicum annuum are promising native plants with the potential to be used in the phytoremediation of soils in tropical areas that are impacted by mining. PMID- 26556742 TI - Dietary magnesium intake, bone mineral density and risk of fracture: a systematic review and meta-analysis. AB - Dietary magnesium intake has been related to osteoporosis and risk of fractures in earlier studies; however, findings were conflicting. This meta-analysis indicated that high magnesium intake was not associated with increased risk of fracture; however, a positive marginally significant correlation was found between magnesium intake and bone mineral density (BMD) in total hip as well as in femoral neck. Although there is some evidence on the association between magnesium intake, BMD and fractures, no previous study has summarized findings in this regard. We aimed to systematically review the current evidence on this association and to perform a meta-analysis of observational studies. We searched MEDLINE, Scopus, EMBASE and Google Scholar up to January 2015 for studies that examined the relationship between magnesium intake and BMD or fracture. Studies that had reported correlation coefficients between magnesium intake and BMD or those that reported odds ratios (ORs) or relative risks (RRs) for risk of fracture in different sites were included. In total, 12 studies were included in the meta-analysis. We found that high intakes of magnesium were not significantly associated with risk of total hip fracture (summary effect size 1.92; 95 % CI 0.81, 4.55) or total fractures (1.01; 0.94-1.07). Combining four effect sizes, a positive marginally significant correlation was observed between magnesium intake and total BMD (pooled r 0.16; 95 % CI 0.001, 032). Based on nine effect sizes, we found a marginally significant association between magnesium intake and femoral neck BMD (0.14; 0.001, 0.28). However, no significant correlation was found between magnesium intake and BMD in lumbar spine (0.09; -0.01, 0.19). We found that high intakes of magnesium were not associated with increased risk of hip and total fractures. There was a positive marginally significant correlation between magnesium intake and BMD in femoral neck and total hip. No significant correlations were observed between magnesium intake and BMD in lumbar spine. PMID- 26556745 TI - Characterization of successional changes in bacterial community composition during bioremediation of used motor oil-contaminated soil in a boreal climate. AB - The widespread use of motor oil makes it a notable risk factor to cause scattered contamination in soil. The monitoring of microbial community dynamics can serve as a comprehensive tool to assess the ecological impact of contaminants and their disappearance in the ecosystem. Hence, a field study was conducted to monitor the ecological impact of used motor oil under different perennial cropping systems (fodder galega, brome grass, galega-brome grass mixture and bare fallow) in a boreal climate zone. Length heterogeneity PCR characterized a successional pattern in bacterial community following oil contamination over a four-year bioremediation period. Soil pH and electrical conductivity were associated with the shifts in bacterial community composition. Crops had no detectable effect on bacterial community composition or complexity. However, the legume fodder galega increased soil microbial biomass, expressed as soil total DNA. Oil contamination induced an abrupt change in bacterial community composition at the early stage, yet the effect did not last as long as the oil in soil. The successional variation in bacterial community composition can serve as a sensitive ecological indicator of oil contamination and remediation in situ. PMID- 26556746 TI - Dietary items as possible sources of (137)Cs in large carnivores in the Gorski Kotar forest ecosystem, Western Croatia. AB - The mountain forest ecosystem of Gorski Kotar is distant from any significant sources of environmental pollution, though recent findings have revealed that this region is among the most intense (137)Cs contaminated area in Croatia. Therefore, the aim of this study was to investigate (137)Cs and (40)K load in three large predator species in the mountain forest ecosystem. Radionuclides mass activities were determined by the gamma-spectrometric method in the muscle tissue of brown bear (47), wolf (7), lynx (1) and golden jackal (2). The highest (137)Cs mass activity was found in lynx (153 Bq kg(-1)), followed by brown bear (132 Bq kg(-1)), wolf (22.2 Bq kg(-1)), and golden jackal (2.48 Bq kg(-1)). Analysis of 63 samples of dietary items suggests that they are not all potentially dominant sources of (137)Cs for wildlife. The most important source of radionuclides for the higher parts of the food-chain from the study area were found to be the mushroom species wood hedgehog (Hydnum repandum), with a transfer factor TF of 5.166, and blueberry (Vaccinium myrtillus) as a plant species (TF=2.096). Food items of animal origin indicated higher mass activity of radionuclides and therefore are possible moderate bioindicators of environmental pollution. The results also revealed that possible unknown wild animal food sources are a caesium source in the study region, and further study is required to illuminate this issue. PMID- 26556747 TI - Kinetics of phosphorus release from sediments and its relationship with iron speciation influenced by the mussel (Corbicula fluminea) bioturbation. AB - The effects of bivalve (Corbicula fluminea) bioturbation on the lability of phosphorus (P) in sediments were investigated. The high-resolution dialysis (HR Peeper) and diffusive gradients in thin films (DGT) techniques were employed to obtain soluble and labile P/Fe profiles at a vertical resolution of 2 and 1mm, respectively. The bivalve bioturbation increased the concentrations of soluble reactive P (SRP) in pore water and DGT-labile P up to 116% and 833% of the control within the sediment depths from the sediment water interface (SWI) to -64 mm and -44 mm, respectively. The sediments with bioturbation had a smaller distribution coefficient than the control (1964 vs. 3010 cm(3) g(-1)), reflecting a weaker ability in retaining P. Meanwhile, the sediments with bioturbation had a greater ratio of the concentration of DGT-labile P to that of SRP (0.20 vs. 0.03), demonstrating a stronger ability to resupply pore water SRP by the sediment solids when they are affected by the bioturbation. The DGT-induced fluxes in sediments (DIFS) modeling further showed a much shorter response time (277.9 vs. 18,670 s) and a much higher rate (0.192 vs. 0.002 day(-1)) of the solids in release of P with the bioturbation. Correspondingly, the flux of P to the overlying water from the bioturbation treatment increased up to 157% of the control. The bivalve bioturbation significantly increased the concentrations of soluble Fe(II) and DGT-labile Fe up to 84% and 334% of the control from the SWI to -46 mm, respectively. The SRP and DGT-labile P were highly correlated with respective soluble and DGT-labile Fe. It was concluded that the release of P from the sediments with bioturbation to the pore water and the overlying water was promoted by the reductive dissolution of easily reducible Fe(oxyhydr)oxides due to the depletion of oxygen in the top sediments from bivalve respiration. PMID- 26556748 TI - Association of urban particle numbers and sources with lung function among children with asthma or allergies. AB - Previous studies have reported sources of particle number pollution in urban air, but have not evaluated relationships between respiratory health and these sources. We compared, among children with asthma or allergies, the associations of spirometric lung functions with increased exposure to source-specific versus size-segregated particle number concentrations (PNC). Hourly measurements of PNC were acquired from the aerosol Supersite in New Taipei, Taiwan. Spirometry (FVC, FEV1, and FEF) was recorded monthly for 59 children with asthma or allergies at five schools during 2007-2008. After co-pollutant adjustment for ozone, we found a 0.21 and 0.17 L decrease in FVC [95% confidence interval (CI): -0.35, -0.06 L] and FEV1 (95% CI: -0.32, -0.03 L), respectively, with an interquartile range increase (1879.7#/cm(3)) in secondary aerosol contribution observed on the previous day. In addition, we found no significant associations of FVC with accumulation mode (0.1 MUm=0.9991) was obtained for all the matrix calibration curves within a range of 0.1 to 10 mg L(-1). The limits of detection for both enantiomers were estimated to be 0.008 mg kg(-1) in soil, cucumber, spinach and tomato and 0.012 mg kg(-1) in apple and peach, which were lower than the maximum residue levels established in Japan. The results indicate that the proposed method is convenient and reliable for the enantioselective detection of ethiprole in agricultural and environmental samples. The behavior of ethiprole in soil was studied under field conditions and the enantioselective degradation was observed with enantiomer fraction values varying from 0.494 to 0.884 during the experiment. The (R)-(+)-ethiprole (t1/2=11.6 d) degraded faster than (S)-(-) ethiprole (t1/2=34.7 d). This report is the first describe a chiral analytical method and enantioselective behavior of ethiprole, and these results should be extremely useful for the risk evaluation of ethiprole in food and environmental safety. PMID- 26556750 TI - Septic tank discharges as multi-pollutant hotspots in catchments. AB - Small point sources of pollutants such as septic tanks are recognised as significant contributors to streams' pathogen and nutrient loadings, however there is little data in the UK on which to judge the potential risks that septic tank effluents (STEs) pose to water quality and human health. We present the first comprehensive analysis of STE to help assess multi-pollutant characteristics, management-related risk factors and potential tracers that might be used to identify STE sources. Thirty-two septic tank effluents from residential households located in North East of Scotland were sampled along with adjacent stream waters. Biological, physical, chemical and fluorescence characterisation was coupled with information on system age, design, type of tank, tank management and number of users. Biological characterisation revealed that total coliforms and Escherichia coli (E. coli) concentration ranges were: 10(3)-10(8) and 10(3)-10(7)MPN/100 mL, respectively. Physical parameters such as electrical conductivity, turbidity and alkalinity ranged 160-1730 MUS/cm, 8-916 NTU and 15-698 mg/L, respectively. Effluent total phosphorus (TP), soluble reactive P (SRP), total nitrogen (TN) and ammonium-N (NH4-N) concentrations ranged 1-32, <1-26, 11-146 and 2-144 mg/L, respectively. Positive correlations were obtained between phosphorus, sodium, potassium, barium, copper and aluminium. Domestic STE may pose pollution risks particularly for NH4-N, dissolved P, SRP, copper, dissolved N, and potassium since enrichment factors were >1651, 213, 176, 63, 14 and 8 times that of stream waters, respectively. Fluorescence characterisation revealed the presence of tryptophan peak in the effluent and downstream waters but not detected upstream from the source. Tank condition, management and number of users had influenced effluent quality that can pose a direct risk to stream waters as multiple points of pollutants. PMID- 26556751 TI - Characteristics of N2O production and transport within soil profiles subjected to different nitrogen application rates in China. AB - To better understand the effect of N fertilizer on the responses of subsoil N2O to N2O emissions in a high-yield plot, we investigated the subsurface N2O concentrations at seven mineral soil depths and analyzed the subsoil N2O fluxes between soil horizons. This study was conducted from 2012 to 2013 in farmland located in the semi-humid area of the Changwu station, Shaanxi, and the results showed that the application of N fertilizer triggered the highest amount of N2O production and effluxes in the various soil layers. With an increase of N fertilizer, N2O effluxes and production significantly increased; the mean variation of 380 kg N ha(-1) treatment was much greater than that of 250 kg N ha( 1) treatment, particularly after fertilization during the maize growing season (MS). N2O concentrations increased within 30 cm and maintained low and stable values. However, N2O fluxes and production decreased with depth (below 30 cm) and then remained low (approximately zero or even negative) at depths of 30-90 cm. The cumulative N2O fluxes in the 0-15 cm soil layer accounted for 99.0% of the total amount in the soil profile, and high fluxes coincided with periods of relatively high production rates. The cumulative production of N2O also remained in step with the cumulative fluxes. In addition, more N fertilizer was applied, greater production occurred in the topsoil. A significantly positive relationship was found between N2O fluxes and mineral N, and a negative relationship was found between the fluxes and the water-filled pore space (WFPS) in the shallow soil. N2O effluxes increased with increasing amounts of N fertilizer, which was primarily due to nitrification on the Loess Plateau. PMID- 26556752 TI - Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus-pituitary-thyroid axis in zebrafish embryos. AB - Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 MUg/L) of bifenthrin (BF) or lambda cyhalothrin (lambda-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus-pituitary-thyroid (HPT) axis examined. Body weight was significantly decreased in the lambda-CH exposure groups, but not the BF exposure groups. BF and lambda-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T4) and triiodothyronine (T3) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSHbeta, TTR, UGT1ab, Pax8, Dio2 and TRalpha, were significantly upregulated in the presence of BF. Compared to BF, lambda-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRalpha levels along with concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TRalpha) protein more potently than lambda-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and lambda-CH have the potential to disrupt thyroid endocrine system. PMID- 26556753 TI - Elucidation of rice rhizosphere metagenome in relation to methane and nitrogen metabolism under elevated carbon dioxide and temperature using whole genome metagenomic approach. AB - Carbon (C) and nitrogen (N) mineralization is one of the key processes of biogeochemical cycling in terrestrial ecosystem in general and rice ecology in particular. Rice rhizosphere is a rich niche of microbial diversity influenced by change in atmospheric temperature and concentration of carbon dioxide (CO2). Structural changes in microbial communities in rhizosphere influence the nutrient cycling. In the present study, the bacterial diversity and population dynamics were studied under ambient CO2 (a-CO2) and elevated CO2+temperature (e-CO2T) in lowland rice rhizosphere using whole genome metagenomic approach. The whole genome metagenomic sequence data of lowland rice exhibited the dominance of bacterial communities including Proteobacteria, Firmicutes, Acidobacteria, Actinobacteria and Planctomycetes. Interestingly, four genera related to methane production namely, Methanobacterium, Methanosphaera, Methanothermus and Methanothermococcus were absent in a-CO2 but noticed under e-CO2T. The acetoclastic pathway was found as the predominant pathway for methanogenesis, whereas, the serine pathway was found as the principal metabolic pathway for CH4 oxidation in lowland rice. The abundances of reads of enzymes in the acetoclastic methanogenesis pathway and serine pathways of methanotrophy were much higher in e CO2T (328 and 182, respectively) as compared with a-CO2 (118 and 98, respectively). Rice rhizosphere showed higher structural diversities and functional activities in relation to N metabolism involving nitrogen fixation, assimilatory and dissimilatory nitrate reduction and denitrification under e-CO2T than that of a-CO2. Among the three pathways of N metabolism, dissimilarity pathways were predominant in lowland rice rhizosphere and more so under e-CO2T. Consequently, under e-CO2T, CH4 emission, microbial biomass nitrogen (MBN) and dehydrogenase activities were 45%, 20% and 35% higher than a-CO2, respectively. Holistically, a high bacterial diversity and abundances of C and N decomposing bacteria in lowland rice rhizosphere were found under e-CO2T, which could be explored further for their specific role in nutrient cycling, sustainable agriculture and environment management. PMID- 26556754 TI - PAHs and PCBs accumulated by SPMD-based virtual organisms and feral fish in Three Gorges Reservoir, China. AB - Polycyclic aromatic hydrocarbon (PAHs) and polychlorinated biphenyls (PCBs) accumulated by semipermeable membrane device (SPMD)-based virtual organisms (VOs) and local feral fish were studied in Three Gorges Reservoir (TGR), China. VOs were deployed at seven sites in TGR for two periods in 2009 and 5 species of fish with different living habitats and feeding habits collected in the same periods from two counties in TGR. The concentration and profile of PAHs and PCBs in fish were quite different from those in VOs. Most high-molecular-weight-PAHs were detected in VOs, while they were undetected in fish. Most PCBs were undetected in VOs, while most of them were detected in fish. Low-molecular-weight-PAHs were predominant contaminants of PAHs and non-dioxin-like-PCBs were the main PCBs in fish. The levels of PAHs and PCBs in the few fish samples were low and were not of concern based on chemical contaminant limits of non-carcinogenic effect. PMID- 26556755 TI - Lead concentration in the blood of the general population living near a lead-zinc mine site, Nigeria: Exposure pathways. AB - Lead (Pb) poisoning in children is a major public health catastrophe worldwide. This report summarises both exposure pathways and blood Pb levels in children below 7 years of age and adults (above 18 years) from the Adudu community living near a lead-zinc mine in Nasawara, Nigeria. The average and median blood Pb levels in children and adults were 2.1 and 1.3 MUg/dL, 3.1 and 1.8 MUg/dL, respectively. However, Pb in 14% of adults' blood exceeded 5 MUg/dL, which is the recommended threshold blood Pb concentration in adults as established by the Centers for Disease Control and Prevention (CDC). Furthermore 68% of adults' blood exceeded blood Pb action level of 2 MUg/dL. For children, 11.4% and 31% of the blood samples exceeded 5 MUg/dL and 2 MUg/dL, respectively, while no safe blood Pb level in children has been recommended. In Nasawara, a significant difference (p<0.05) was observed between the various age groups in children with 2-4 years old having the highest levels and 6 year old children having the lowest Pb levels. Although this study did not detect elevated levels of Pb in children's blood in regions such as Zamfara, Nigeria and Kabwe, Zambia, a high percentage of samples exceeded 2 MUg/dL. Soils, floor dusts, water and crops also reveal that Pb contamination in the study area could potentially be the major cause of blood Pb in the community exposed to mining. This study also observed a significant correlation between water Pb levels of adults and blood Pb levels, suggesting that water is the major exposure pathway. This analysis highlights the need to properly manage mining activities so that the health of communities living in the vicinity of a Pb-Zn mine is not compromised. PMID- 26556757 TI - Fabrication of transparent SERS platform via interface self-assembly of gold nanorods and gel trapping technique for on-site real time detection. AB - A transparent SERS platform was fabricated via the gel-trapping method coupled with a liquid/liquid interface self-assembly technique. We employed gold nanorods as the building blocks for interface self-assembly because of their strong localized surface plasmons upon excitation by infrared radiation. Based on a "top cover" configuration, this transparent SERS platform endows high signal reproducibility for directly detecting liquid samples by confining the sample droplet into a regular shape. The Au NR PDMS platform was able to directly detect crystal violet in aqueous solutions down to 10 ppb level with high enhancement factor (0.87 * 10(5)) and signal uniformity (RSD = 3.9%). Furthermore, SERS-based anti-fungal agent detection on a fish scale was demonstrated by simply covering the fish scale with a tailored GNRs PDMS film. The experimental results clearly show that the Au NR PDMS SERS platform has great potential for on-site real time detection of contaminants in water as well as on curved surfaces. PMID- 26556756 TI - Improving Multi-Epitope Long Peptide Vaccine Potency by Using a Strategy that Enhances CD4+ T Help in BALB/c Mice. AB - Peptide-based vaccines are attractive approaches for cancer immunotherapy; but the success of these vaccines in clinical trials have been limited. Our goal is to improve immune responses and anti-tumor effects against a synthetic, multi epitope, long peptide from rat Her2/neu (rHer2/neu) using the help of CD4+ T cells and appropriate adjuvant in a mouse tumor model. Female BALB/c mice were vaccinated with P5+435 multi-epitope long peptide that presents epitopes for cytotoxic T lymphocytes (CTL) in combination with a universal Pan DR epitope (PADRE) or CpG-oligodeoxynucleotides (CpG-ODNs) as a Toll-like receptor agonist adjuvant. The results show that vaccination with the multi-epitope long peptide in combination with the PADRE peptide and CpG-ODN induced expansion of subpopulations of CD4+ and CD8+ cells producing IFN-gamma, the average tumor size in the vaccinated mice was less than that of the other groups, and tumor growth was inhibited in 40% of the mice in the vaccinated group. The mean survival time was 82.6 +/- 1.25 days in mice vaccinated with P5+435 + CpG+ PADRE. Our results demonstrate that inclusion of PADRE and CpG with the peptide vaccine enhanced significant tumor specific-immune responses in vaccinated mice. PMID- 26556758 TI - The Elementary Operations of Human Vision Are Not Reducible to Template-Matching. AB - It is generally acknowledged that biological vision presents nonlinear characteristics, yet linear filtering accounts of visual processing are ubiquitous. The template-matching operation implemented by the linear-nonlinear cascade (linear filter followed by static nonlinearity) is the most widely adopted computational tool in systems neuroscience. This simple model achieves remarkable explanatory power while retaining analytical tractability, potentially extending its reach to a wide range of systems and levels in sensory processing. The extent of its applicability to human behaviour, however, remains unclear. Because sensory stimuli possess multiple attributes (e.g. position, orientation, size), the issue of applicability may be asked by considering each attribute one at a time in relation to a family of linear-nonlinear models, or by considering all attributes collectively in relation to a specified implementation of the linear-nonlinear cascade. We demonstrate that human visual processing can operate under conditions that are indistinguishable from linear-nonlinear transduction with respect to substantially different stimulus attributes of a uniquely specified target signal with associated behavioural task. However, no specific implementation of a linear-nonlinear cascade is able to account for the entire collection of results across attributes; a satisfactory account at this level requires the introduction of a small gain-control circuit, resulting in a model that no longer belongs to the linear-nonlinear family. Our results inform and constrain efforts at obtaining and interpreting comprehensive characterizations of the human sensory process by demonstrating its inescapably nonlinear nature, even under conditions that have been painstakingly fine-tuned to facilitate template-matching behaviour and to produce results that, at some level of inspection, do conform to linear filtering predictions. They also suggest that compliance with linear transduction may be the targeted outcome of carefully crafted nonlinear circuits, rather than default behaviour exhibited by basic components. PMID- 26556760 TI - Quantitative Analysis of Hexahydro-1,3,5-trinitro-1,3,5, Triazine/Pentaerythritol Tetranitrate (RDX-PETN) Mixtures by Terahertz Time Domain Spectroscopy. AB - Absorption spectra of explosives such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), pentaerythritol tetranitrate (PETN), and mixtures of both were measured by terahertz time domain spectroscopy (THz-TDS). Chemometrics was applied to quantitative analysis of terahertz absorbance spectra obtained in transmission mode to predict the relative amounts of RDX and PETN in samples containing pure components or their mixtures. This analysis was challenging because significant spectral overlap prevented identification of each product fingerprint. Partial least squares (PLS) regression models were thus applied to the terahertz spectra. A comparison between the so-called PLS1 and PLS2 algorithms was performed to predict the PETN concentrations in mixture samples. PLS2 demonstrated better predictive ability than PLS1 with RMSE value lower than 3.5 mg for 400 mg total weight pellets. Moreover, the influence of the highly overlapping spectral frequency band was investigated by reducing the original 0.2-3 THz (6-100 cm(-1)) spectral band to 1.8-3 THz (60-100 cm(-1)). The predictive ability was quite similar in both cases, highlighting the excellent ability of chemometrics to perform quantitative analysis when applied to THz-TDS data, even in the case of highly overlapping spectra. PMID- 26556759 TI - Acute and Chronic Ethanol Administration Differentially Modulate Hepatic Autophagy and Transcription Factor EB. AB - BACKGROUND: Chronic ethanol (EtOH) consumption decelerates the catabolism of long lived proteins, indicating that it slows hepatic macroautophagy (hereafter called autophagy) a crucial lysosomal catabolic pathway in most eukaryotic cells. Autophagy and lysosome biogenesis are linked. Both are regulated by the transcription factor EB (TFEB). Here, we tested whether TFEB can be used as a singular indicator of autophagic activity, by quantifying its nuclear content in livers of mice subjected to acute and chronic EtOH administration. We correlated nuclear TFEB to specific indices of autophagy. METHODS: In acute experiments, we gavaged GFP-LC3(tg) mice with a single dose of EtOH or with phosphate buffered saline (PBS). We fed mice chronically by feeding them control or EtOH liquid diets. RESULTS: Compared with PBS-gavaged controls, livers of EtOH-gavaged mice exhibited greater autophagosome (AV) numbers, a higher incidence of AV-lysosome co-localization, and elevated levels of free GFP, all indicating enhanced autophagy, which correlated with a higher nuclear content of TFEB. Compared with pair-fed controls, livers of EtOH-fed mice exhibited higher AV numbers, but had lower lysosome numbers, lower AV-lysosome co-localization, higher P62/SQSTM1 levels, and lower free GFP levels. The latter findings correlated with lower nuclear TFEB levels in EtOH-fed mice. Thus, enhanced autophagy after acute EtOH gavage correlated with a higher nuclear TFEB content. Conversely, chronic EtOH feeding inhibited hepatic autophagy, associated with a lower nuclear TFEB content. CONCLUSIONS: Our findings suggest that the effect of acute EtOH gavage on hepatic autophagy differs significantly from that after chronic EtOH feeding. Each regimen distinctly affects TFEB localization, which in turn, regulates hepatic autophagy and lysosome biogenesis. PMID- 26556761 TI - Kinesin motors in plants: from subcellular dynamics to motility regulation. AB - Plants produce enormous forms of the microtubule (MT)-based motor kinesins that have been inspiring plant cell biologists to uncover their functions in relation to plant growth and development. Subcellular localization of kinesin proteins detected through live-cell imaging or immunofluorescence microscopy has provided great insights into the functions of these motors. Dozens of mitotic kinesins exhibit particularly splendid localization patterns from chromosomes and kinetochores to MT arrays like the preprophase band, spindle poles, the spindle midzone, phragmoplast distal ends, and the phragmoplast midzone. Different subcellular localizations indicate distinct functions of these motors that are yet to be characterized. The localization difference between plant kinesins and their animal counterparts implies mechanistic differences in mitosis and cytokinesis between the two kingdoms. When many forms of kinesins are present simultaneously, it becomes critical that their motility is differentially regulated with spatial and temporal precision. Insights into regulatory mechanisms of motors can often be brought about by in vitro single-molecule biophysical studies. Significant advances are expected in this area in the coming years owing to rapid technological advances that are being brought to various model plants. PMID- 26556762 TI - The effect of retinol binding protein on the proteome of C2C12 muscle cells. AB - BACKGROUND: Retinol binding protein (RBP) and its membrane receptor, STRA6, are vital for the management of vitamin A in the body. Recently, elevated serum RBP levels have been implicated as a contributing factor to the development of insulin resistance and type 2 diabetes. However, conflicting opinions exist as to how these increased levels can cause insulin resistance. METHODS: In order to better understand the influences of RBP, a proteomic study was devised to determine the direct effect of RBP on a mouse muscle cell line, because the muscle is the principal site of insulin induced glucose uptake. C2C12 cells were treated with RBP for 16 h and the proteome analysed for alterations in protein abundance and phosphorylation by 2-DE. RESULTS: A number of changes were observed in response to retinol binding protein treatment, of which the most interesting were decreased levels of the phosphatase, protein phosphatase 1 beta. This phosphatase is responsible for regulating glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes involved in glycogen storage and utilization. Retinol binding protein treatment resulted in increased phosphorylation and inhibition of glycogen synthase, with detrimental effects on insulin stimulated glycogen production in these cells. CONCLUSION: The results indicate that RBP may have a negative effect on energy storage in the cell and could contribute to the development of insulin resistance in muscle tissue. Understanding how retinol binding protein influences insulin resistance may reveal novel strategies to target this disease. PMID- 26556763 TI - Arcobacter pacificus sp. nov., isolated from seawater of the South Pacific Gyre. AB - A Gram-stain-negative, rod-shaped, slightly curved, non-spore-forming strain, designated SW028T, was isolated from surface seawater (26 degrees 29' S 137 degrees 56' W) of the South Pacific Gyre during the Integrated Ocean Drilling Program Expedition 329. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SW028T belonged to the genus Arcobacter and it showed the highest sequence similarity with Arcobacter molluscorum LMG 25693T (95.50 %). The dominant fatty acids of strain SW028T were C18 : 1omega7c, C16 : 1omega7c and C16 : 0. The only respiratory quinone detected was menaquinone-6. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content was 27.1 mol%. The phylogenetic position of the novel strain was further confirmed by analysis of the housekeeping genes rpoB, gyrB and atpA. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain SW028T represents a novel species of the genus Arcobacter, for which the name Arcobacter pacificus is proposed. The type strain is SW028T ( = DSM 25018T = JCM 17857T = LMG 26638T = CGMCC NO.1.11011T). PMID- 26556764 TI - Direct solvothermal preparation of nanostructured fluoride aerogels based on AlF3. AB - AlF3-based aerogels, a new class of inorganic aerogels, are prepared in a novel direct process that combines fluoride sol-gel synthesis with high temperature supercritical drying. The bulk structure of the solid products depends decisively on the applied solvent(s); very voluminous bulk aerogels are obtained only with MeOH that is used either alone or in combination with some other polar solvents. MeOH acts as a methoxylation agent; and formed methoxy (MeO) species are remarkably stable and deactivate the surface acidic sites. Removal of MeO species under moderate conditions results in catalytically active fluorides with a preserved nanostructure. In preparations with MeOH, preferential growth of anisotropic nanoparticles (nanorods) is the key step that leads to the formation of very open aerogel structures. Another process, dehydration of alcohols, results in some hydroxylation and hydration that lead to the formation of distinctive surface and bulk OH/H2O species. The structure of AlF3-based aerogels is consistent with the hexagonal tungsten bronze (HTB) beta-AlF3 although their composition corresponds to a formula AlF3-x(OH, OMe)x.yH2O (x = 0.1 +/- 0.05). Some other characteristics of the fluoride nanoparticles, like crystallinity, particle size, and uniformity, can be effectively controlled by the temperature of the solvothermal process. The described methodology allows a controllable preparation of catalytically active fluorides in the form of regularly shaped and uniformly sized nanoparticles. PMID- 26556765 TI - The nuances of NO synthase regulation in sepsis: Could targeting BH4 be the answer? PMID- 26556767 TI - Urinary diversions: A time to enrich surgical training? AB - OBJECTIVE: To assess the potential exposure to complex urologic procedures, specifically urinary diversion, during a gynecologic oncology fellowship. METHODS: We queried the University HealthSystem Consortium (UHC) database to determine the total number of urinary diversions performed from October 2008 to August 2012. This data was used to estimate the mean number of urinary diversions performed each year. Gender, primary diagnosis, type of diversion, gynecologic oncologist involvement, and medical center were explored. RESULTS: Of the nearly 21,000 urinary diversions performed in UHC participating hospitals during the study period, 6180 (29.5%) were performed in women. On average, 1648 urinary diversions are performed in women each year, with gynecologic malignancies accounting for 6.8% of cases. We estimate that a gynecologic oncologist was involved with 87 cases per year at nonprofit academic medical centers in the US. With approximately 112 clinically active fellows per year during the study period, this equates to less than one diversion per clinical fellow per year if cases are equally distributed among centers. However, the majority of urinary diversions with gynecologic oncologist involvement were performed at just a fraction of centers. Thus, only a small contingent of fellows may be getting the greatest exposure to urinary diversions. CONCLUSIONS: The majority of urinary diversions in women in the US are performed for bladder carcinoma by urologists. The estimated number of cases per clinical gynecologic oncology fellow per year is less than one. Strategies to improve fellow exposure to urinary diversion and consideration of alternative surgical training modalities should be explored. PMID- 26556766 TI - Chemotherapy-induced peripheral neuropathy: Current status and progress. AB - As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. PMID- 26556769 TI - Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status. AB - OBJECTIVES: After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12 years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors. METHODS: We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10 years for a range of factors including BRCA mutation status and extent of residual disease post-surgery. RESULTS: Of the 1421 patients, 109 (7.7%) had BRCA1 mutations and 68 (4.8%) had BRCA2 mutations. A status of no residual disease was achieved by 39% of non-carriers and 19% of mutation carriers (P<0.0001). By 10-years of follow-up, 43% of non-carriers, 57% of BRCA1 mutation carriers and 69% of BRCA2 mutation carriers had died from ovarian cancer. Among women with stage III/IV serous cancers and no residual disease, the 10-year actuarial survival was 42% for non-carriers and 29% for mutation carriers (P=0.40). CONCLUSION: The initial survival advantage among women with BRCA mutations may reflect a higher initial sensitivity of BRCA carriers to chemotherapy, but this response does not predict long-term survival. The strongest predictor of long-term survival is status of no residual disease at resection. PMID- 26556768 TI - Maintaining sexual health throughout gynecologic cancer survivorship: A comprehensive review and clinical guide. AB - OBJECTIVE: The diagnosis and treatment of gynecologic cancer can cause short- and long-term negative effects on sexual health and quality of life (QoL). The aim of this article is to present a comprehensive overview of the sexual health concerns of gynecologic cancer survivors and discuss evidence-based treatment options for commonly encountered sexual health issues. METHODS: A comprehensive literature search of English language studies on sexual health in gynecologic cancer survivors and the treatment of sexual dysfunction was conducted in MEDLINE databases. Relevant data are presented in this review. Additionally, personal and institutional practices are incorporated where relevant. RESULTS: Sexual dysfunction is prevalent among gynecologic cancer survivors as a result of surgery, radiation, and chemotherapy-negatively impacting QoL. Many patients expect their healthcare providers to address sexual health concerns, but most have never discussed sex-related issues with their physician. Lubricants, moisturizers, and dilators are effective, simple, non-hormonal interventions that can alleviate the morbidity of vaginal atrophy, stenosis, and pain. Pelvic floor physical therapy can be an additional tool to address dyspareunia. Cognitive behavioral therapy has been shown to be beneficial to patients reporting problems with sexual interest, arousal, and orgasm. CONCLUSION: Oncology providers can make a significant impact on the QoL of gynecologic cancer survivors by addressing sexual health concerns. Simple strategies can be implemented into clinical practice to discuss and treat many sexual issues. Referral to specialized sexual health providers may be needed to address more complex problems. PMID- 26556770 TI - Decorin alleviated chronic hydrocephalus via inhibiting TGF-beta1/Smad/CTGF pathway after subarachnoid hemorrhage in rats. AB - Chronic hydrocephalus is one of the severe complications after subarachnoid hemorrhage (SAH). However, there is no efficient treatment for the prevention of chronic hydrocephalus, partially due to poor understanding of underlying pathogenesis, subarachnoid fibrosis. Transforming growth factor-beta1(TGF-beta1) is a potent fibrogenic factor implicated in wide range of fibrotic diseases. To investigate whether decorin, a natural antagonist for TGF-beta1, protects against subarachnoid fibrosis and chronic hydrocephalus after SAH, two-hemorrhage injection SAH model was conducted in 6-week-old rats. Recombinant human decorin(rhDecorin) (30ug/2ul) was administered before blood injection and on the 10th day after SAH. TGF-beta1, p-Smad2/3, connective tissue growth factor (CTGF), collagen I and pro-collagen I c-terminal propeptide were assessed via western blotting, enzyme-linked immunosorbent assay, radioimmunoassay and immunofluorescence. And neurobehavioral tests and Morris water maze were employed to evaluate long-term neurological functions after SAH. We found that SAH induced heightened activation of TGF-beta1/Smad/CTGF axis, presenting as a two peak response of TGF-beta1 in cerebrospinal fluid, elevation of TGF-beta1, p-Smad2/3, CTGF, collagen I in brain parenchyma and pro-collagen I c-terminal propeptide in cerebrospinal fluid, and increased lateral ventricle index. rhDecorin treatment effectively inhibited up-regulation of TGF-beta1, p-Smad2/3, CTGF, collagen I and pro-collagen I c-terminal propeptide after SAH. Moreover, rhDecorin treatment significantly reduced lateral ventricular index and incidence of chronic hydrocephalus after SAH. Importantly, rhDecorin improved neurocognitive deficits after SAH. In conclusion, rhDecorin suppresses extracellular matrix accumulation and following subarachnoid fibrosis via inhibiting TGF-beta1/Smad/CTGF pathway, preventing development of hydrocephalus and attenuating long-term neurocognitive defects after SAH. PMID- 26556771 TI - Neuroglobin immunoreactivity in the human cochlea. AB - Neuroglobin (Ngb) is an oxygen-binding protein with a demonstrated role in endogenous neuroprotective mechanisms. It has been shown to function as a scavenger for reactive oxidizing species thereby assisting in cellular defense against oxidative stress. In the present study, we characterized the presence of Ngb in the human cochlea. Immunohistochemical staining was performed on formalin fixed celloidin human cochlea sections obtained from human temporal bones, using affinity purified polyclonal antibodies against Ngb. Thirty-six temporal bones were analyzed, 15 with normal otologic histories and 21 diagnosed with different inner ear pathologies. Ngb immunoreactivity (Ngb-IR) was consistently expressed in the neurons of spiral ganglia (SG) and supporting cells of the organ of Corti. There was a significant decrease of Ngb-IR in SGNs from specimens with inner ear pathologies when compared to normal specimens. In contrast, Ngb-IR in the organ of Corti did not show significant changes between pathological and normal specimens. The differential pattern of Ngb expression in these cochlear structures suggests that Ngb may participate in defense mechanisms in inner ear pathologies where oxidative stress is involved. PMID- 26556773 TI - What works in auditory working memory? A neural oscillations perspective. AB - Working memory is a limited resource: brains can only maintain small amounts of sensory input (memory load) over a brief period of time (memory decay). The dynamics of slow neural oscillations as recorded using magneto- and electroencephalography (M/EEG) provide a window into the neural mechanics of these limitations. Especially oscillations in the alpha range (8-13Hz) are a sensitive marker for memory load. Moreover, according to current models, the resultant working memory load is determined by the relative noise in the neural representation of maintained information. The auditory domain allows memory researchers to apply and test the concept of noise quite literally: Employing degraded stimulus acoustics increases memory load and, at the same time, allows assessing the cognitive resources required to process speech in noise in an ecologically valid and clinically relevant way. The present review first summarizes recent findings on neural oscillations, especially alpha power, and how they reflect memory load and memory decay in auditory working memory. The focus is specifically on memory load resulting from acoustic degradation. These findings are then contrasted with contextual factors that benefit neural as well as behavioral markers of memory performance, by reducing representational noise. We end on discussing the functional role of alpha power in auditory working memory and suggest extensions of the current methodological toolkit. This article is part of a Special Issue entitled SI: Auditory working memory. PMID- 26556772 TI - Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy. AB - Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID- 26556774 TI - Transient middle cerebral artery occlusion in mice induces neuronal expression of RNF213, a susceptibility gene for moyamoya disease. AB - Although recent genome-wide and locus-specific association studies revealed that the RING finger protein 213 (RNF213) gene is an important susceptibility gene for moyamoya disease (MMD), the exact mechanism by which the genetic alteration of RNF213 contributes to the development of MMD has not yet been elucidated. A quantitative reverse transcription polymerase chain reaction (PCR) analysis revealed that the constitutive expression of the RNF213 gene was very low in adult and embryonic brain tissue. However, information regarding the temporal and spatial expression patterns of the RNF213 gene under the condition of cerebral ischemia, which is one of characteristic pathologies associated with MMD, is currently limited. In order to address this critical issue, Rnf213 mRNA expression was investigated in mouse brains subjected to 60 min of transient middle cerebral artery occlusion (tMCAO). Male C57BL6/j mice underwent tMCAO through the intraluminal blockade of MCA. Expression of the Rnf213 gene in the tMCAO brain was investigated with in situ RNA hybridization and a real-time PCR analysis from 1 to 72 h after tMCAO. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the cerebral cortex supplied by the affected MCA, especially at the penumbra area, as early as 6h after tMCAO, and these levels had increased further by 24 h. Rnf213 gene expression remained unchanged in the non-ischemic hemisphere or control specimens. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression mostly in neurons. The real-time PCR analysis confirmed induction of the Rnf213 gene after tMCAO. Therefore, the Rnf213 gene was up-regulated in the ischemic brain, especially at the penumbra area, 6 h after tMCAO. Early increases in RNF213 gene expression in neurons after tMCAO indicate its involvement in cerebral ischemia, which is an underlying pathology of MMD. Further investigation is required to clarify its exact role in the pathophysiology of MMD. PMID- 26556775 TI - Observation chart design features affect the detection of patient deterioration: a systematic experimental evaluation. AB - AIM: To systematically evaluate the impact of several design features on chart users' detection of patient deterioration on observation charts with early warning scoring-systems. BACKGROUND: Research has shown that observation chart design affects the speed and accuracy with which abnormal observations are detected. However, little is known about the contribution of individual design features to these effects. DESIGN: A 2 * 2 * 2 * 2 mixed factorial design, with data-recording format (drawn dots vs. written numbers), scoring-system integration (integrated colour-based system vs. non-integrated tabular system) and scoring-row placement (grouped vs. separate) varied within-participants and scores (present vs. absent) varied between-participants by random assignment. METHODS: 205 novice chart-users, tested between March 2011-March 2014, completed 64 trials where they saw real patient data presented on an observation chart. Each participant saw eight cases (four containing abnormal observations) on each of eight designs (which represented a factorial combination of the within participants variables). On each trial, they assessed whether any of the observations were physiologically abnormal, or whether all observations were normal. Response times and error rates were recorded for each design. RESULTS: Participants responded faster (scores present and absent) and made fewer errors (scores absent) using drawn-dot (vs. written-number) observations and an integrated colour-based (vs. non-integrated tabular) scoring-system. Participants responded faster using grouped (vs. separate) scoring-rows when scores were absent, but separate scoring-rows when scores were present. CONCLUSION: Our findings suggest that several individual design features can affect novice chart users' ability to detect patient deterioration. More broadly, the study further demonstrates the need to evaluate chart designs empirically. PMID- 26556776 TI - The clinical effectiveness and cost-effectiveness of open mesh repairs in adults presenting with a clinically diagnosed primary unilateral inguinal hernia who are operated in an elective setting: systematic review and economic evaluation. AB - BACKGROUNDS: Current open mesh techniques for inguinal hernia repair have shown similar recurrence rates. However, chronic pain has been associated with Lichtenstein mesh repair, the most common surgical procedure for inguinal hernia in the UK. The position of the mesh is probably an important factor. The Lichtenstein method requires dissection of the inguinal wall and fixation of the mesh. In contrast, in the open preperitoneal approach the mesh is placed in the preperitoneal space and held in place with intra-abdominal pressure. Currently, there is no consensus regarding the best open approach for repair of inguinal hernia. OBJECTIVES: To determine the clinical effectiveness and cost effectiveness of open preperitoneal mesh repair compared with Lichtenstein mesh repair in adults presenting with a clinically diagnosed primary unilateral inguinal hernia. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed, EMBASE, Cochrane Controlled Trials Register) from inception to November 2014 and contacted experts in the field. REVIEW METHODS: Evidence was considered from randomised controlled trials (RCTs) that compared open preperitoneal mesh repair with Lichtenstein mesh repair for the treatment of inguinal hernia. Two reviewers independently selected studies for inclusion. One reviewer completed data extraction and assessed risk of bias for included studies, and two reviewers independently cross-checked the details extracted. Meta-analyses techniques were used to combine results from included studies. A Markov model was developed to assess the cost-effectiveness of open mesh procedures from a NHS health services perspective over a 25-year time horizon. RESULTS: Twelve RCTs involving 1568 participants were included. Participants who underwent open preperitoneal mesh repair returned to work and normal activities significantly earlier than those who underwent Lichtenstein mesh repair [mean difference -1.49 days, 95% confidence interval (CI) -2.78 to 0.20 days]. Although no significant differences were observed between the two open approaches for incidence of pain [risk ratio (RR) 0.50, 95% CI 0.20 to 1.27], numbness (RR 0.48, 95% CI 0.15 to 1.56), recurrences (Peto odds ratio 0.76, 95% CI 0.38 to 1.52) or postoperative complications, fewer events were generally reported after open preperitoneal mesh repair. The results of the economic evaluation indicate that the open preperitoneal mesh repair was L256 less costly and improved health outcomes by 0.041 quality-adjusted life-years (QALYs) compared with Lichtenstein mesh repair. The open preperitoneal procedure was the most efficient and dominant treatment strategy with a high (> 98%) probability of being cost-effectiveness for the NHS at a willingness to pay of L20,000 for a QALY. Results were robust to a range of sensitivity analyses. However, the magnitude of cost saving or QALY gain was sensitive to some model assumptions. LIMITATIONS: Overall, the included trials were of small sample size (mean 130.7 participants) and at high or unclear risk of bias. Meta-analyses results demonstrated significant statistical heterogeneity for most of the assessed outcomes. CONCLUSIONS: Open preperitoneal mesh repair appears to be a safe and efficacious alternative to Lichtenstein mesh repair. Further research is required to determine the long-term effects of these surgical procedures as well as the most effective open preperitoneal repair technique in terms of both clinical efficacy and costs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013510. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26556777 TI - Exercise Capacity Long-Term after Arterial Switch Operation for Transposition of the Great Arteries. AB - Transposition of the great arteries (TGA) is a congenital heart defect successfully corrected through arterial switch operation (ASO). Although this technique had significant impact in improving survival, little is known about the functional capacity of the operated patients long-term after surgery. OBJECTIVE: The aim of this study was to compare the functional capacity of children with TGA long-term after ASO with that of healthy children. DESIGN: Retrospective study. PATIENTS: All patients that performed cardiopulmonary exercise test (CPET) were included in the study. As a control group, healthy children in evaluation for physical activity that performed CPET during the same period were also enrolled. RESULTS: Thirty-one TGA patients (19 male) were compared with 29 age-matched controls (21 male). Maximum oxygen consumption was higher in the control group (45.47 +/- 8.05 vs. 40.52 +/- 7.19, P = .017), although within normal limits in both groups (above 90% of predicted value). The heart rate behavior during exercise was different in both groups, with a mean chronotropic index significantly lower in the TGA group (63% +/- 14 vs. 81% +/- 12, P < .001). CONCLUSIONS: Our results showed that exercise capacity long-term after ASO in TGA is well preserved although lower than in healthy children what might be explained by the presence of chronotropic incompetence in the TGA group. PMID- 26556778 TI - A randomised assessment of the use of a quality of life questionnaire with or without intervention in patients attending a thoracic cancer clinic. AB - The study examined the impact of using a quality of life (QoL) questionnaire during a clinic to identify QoL issues and to improve QoL. 138 patients were randomised (1:1:1) to either (1) an Intervention group that completed the European Organisation for Research and Treatment of Cancer-Core Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-C30 and LC13) at baseline and received feedback during a clinic, (2) an Attention group that completed the questionnaire at baseline without feedback and (3) a Control group that did not complete the questionnaire. All patients completed the same questionnaire 6 weeks later and a contact diary during the study period. There was a significant difference between the Intervention and Control groups for the mean number of QoL issues identified at baseline (4.69 vs. 2.81, P = 0.006) and the mean number of actions taken (4.41 vs. 2.46, P = 0.004). At 6 weeks, there was no difference between the groups in global QoL (Intervention vs. Control group, P = 0.596; Attention vs. Control, P = 0.973). The results suggest that the completion of the EORTC QLQ-C30 LC13 with feedback improves communication and increases the number of QoL issues identified and actions taken. However, the intervention does not impact on QoL per se. Clinicaltrials.gov: NCT01213745. PMID- 26556780 TI - Insulin pumps improve glucose control in children with type 1 diabetes, study finds. PMID- 26556779 TI - High-Performance Isocyanide Scavengers for Use in Low-Waste Purification of Olefin Metathesis Products. AB - Three isocyanides containing a tertiary nitrogen atom were investigated for use as small-molecule ruthenium scavenging agents in the workup of olefin metathesis reactions. The proposed compounds are odorless, easy to obtain, and highly effective in removing metal residues, sometimes bringing the metal content below 0.0015 ppm. The most successful of the tested compounds, II, performs very well, even with challenging polar products. The performance of these scavengers is compared and contrasted with other known techniques, such as silica gel filtration and the use of self-scavenging catalysts. As a result, a new hybrid purification method is devised, which gives better results than using either a self-scavenging catalyst or a scavenger alone. Additionally, isocyanide II is shown to be a deactivating (reaction quenching) agent for olefin metathesis and superior to ethyl vinyl ether. PMID- 26556781 TI - Longtime undetected microcystic adnexal carcinoma of the scalp: considerations and implications. AB - BACKGROUND: Microcystic adnexal carcinomas (MACs) are slow-growing and often asymptomatic malignant skin tumours that usually develop on the facial skin and may reach considerable size. We present an uncommon case of MAC arising on the hair-bearing scalp and discuss our experiences and considerations. CASE REPORT: A 58-year-old female was admitted with a histopathologically secured diagnosis of MAC of the temporal and occipital regions that had expanded to 10 * 12 cm. Magnetic resonance imaging revealed an infiltration of the skin and the subcutaneous adipose tissue. No lymphatic or haematogenic metastases were detected. Therapy consisted of resecting the tumour and reconstructing the area by applying an anterolateral thigh (ALT) flap. Histopathological evaluation revealed clear, 1-cm margins and a tumour-free periosteum. One-year postoperative follow-ups showed no evidence of recurrence, while the outcome was aesthetically pleasing. CONCLUSION: When screening for skin cancer, careful attention must be paid to the scalp. Resection of MAC with clear margins is mandatory to minimize the risk of recurrence. In this case, applying an ALT perforator flap to a large defect of the hair-bearing scalp led to a very satisfying result; it should be considered in comparable cases. PMID- 26556782 TI - An update on peripheral ossifying fibroma: case report and literature review. AB - The purpose of the present article was to present a clinical case of an 11-year old girl with peripheral ossifying fibroma (POF). Additionally, after performing a literature review, we identified clinical information that occurs more frequently in association with POF, such evidence would help professionals in yielding a specific diagnosis and tailor a more specific therapeutic approach with the objective to decrease morbidities' associated with POF. This lesion represents the third most common lesion of all localized reactive hyperplastic lesions. Clinical aspects related to this pathology include the fact that it occurs most frequently in women between the first and second decades of life. It affects anterior maxillary region and interferes with normal functioning of this anatomical structure. After conducting the literature search, we found that it can also be presented in a considerable number of males with pain and hyperemia being the most common clinical manifestations. We found that often clinical cases are presented with incomplete information. It is important that in order to get to a consensus with respect to updates about information related to this lesion, new case series that include complete clinical information, radiographic analysis, and histopathology tests could be presented. PMID- 26556784 TI - A Qualitative Analysis of Offenders' Modus Operandi in Sexually Exploitative Interactions With Children Online. AB - Transcripts of chat logs of naturally occurring, sexually exploitative interactions between offenders and victims that took place via Internet communication platforms were analyzed. The aim of the study was to examine the modus operandi of offenders in such interactions, with particular focus on the specific strategies they use to engage victims, including discursive tactics. We also aimed to ascertain offenders' underlying motivation and function of engagement in online interactions with children. Five cases, comprising 29 transcripts, were analyzed using qualitative thematic analysis with a discursive focus. In addition to this, police reports were reviewed for descriptive and case specific information. Offenders were men aged between 27 and 52 years ( M = 33.6, SD = 5.6), and the number of children they communicated with ranged from one to 12 ( M = 4.6, SD = 4.5). Victims were aged between 11 and 15 ( M = 13.00, SD = 1.2), and were both female and male. Three offenders committed online sexual offenses, and two offenders committed contact sexual offenses in addition to online sexual offenses. The analysis of transcripts revealed that interactions between offenders and victims were of a highly sexual nature, and that offenders used a range of manipulative strategies to engage victims and achieve their compliance. It appeared that offenders engaged in such interactions for the purpose of sexual arousal and gratification, as well as fantasy fulfillment. PMID- 26556783 TI - Characterization of Transcriptional Repressor Gene MSX1 Variations for Possible Associations with Congenital Heart Diseases. AB - BACKGROUND: The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD. METHODS: We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. RESULTS: Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5'UTR and rs12532 within 3'UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD). CONCLUSIONS: The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations. PMID- 26556785 TI - Differential effect of predictors of bone mineral density and hip geometry in postmenopausal women: a cross-sectional study. AB - Osteoporosis is an important health problem in postmenopausal women. Lactation duration (LD), parity, menopause duration (MD), and body mass index (BMI) are important predictors of bone mineral density (BMD) and osteoporotic fractures in them. In addition, they have site-specific effects on BMD. INTRODUCTION: Osteoporosis is especially prevalent in postmenopausal women. The aim of the study was to determine the effects of age, parity, LD, MD, and BMI on BMD at different sites and hip geometry in postmenopausal women. MATERIALS AND METHODS: In this cross-sectional study, 87 women (45 years and above and at least 5 years postmenopausal) were enrolled. Subjects were divided into three parity groups (group 1: <= 2 children, group: 3-4 children, and group 3: > 4 children) and three LD groups (group 1: < 4 years, group 2: 4-8 years, and group 3: > 8 years). BMD was measured at neck of femur (BMD-NF), trochanter (BMD-TR), inter-trochanter (BMD-IT), spine (BMD-LS), and forearm (BMD-FA). Hip geometry was analyzed based on dual energy X-ray absorptiometry. One way ANOVA was used for comparisons of groups, and Bonferroni correction was used as post-hoc test. p value < 0.05 was considered significant. RESULTS: A significant difference in mean BMD was found between parity groups 1 and 3 at BMD-NF, BMD-TR, and BMD-LS, and between LD groups 1 and 3 at BMD-NF, BMD-TR, BMD-IT, and BMD-LS. Mean buckling ratio (BR) at IT was significantly different between parity groups 1 and 3, and LD groups 1 and 3. In multivariate regression analysis, BMI, age, and parity were significant predictors for BMD-NF; parity, BMI, and MD for BMD-TR; BMI, MD, and LD for BMD IT; BMI and LD for BMD-LS; and age, LD, and BMI for BMD-FA. BMI and LD were significant predictors of IT-BR, while MD and BMI of narrow neck BR. CONCLUSION: MD, LD, parity, BMI, and age are important factors influencing BMD at hip and spine in postmenopausal women, and have site-specific effects on BMD. PMID- 26556786 TI - The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome. AB - BACKGROUND: Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. PURPOSE: We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. PMID- 26556787 TI - [Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase]. AB - BACKGROUND: Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. MATERIAL/METHODS: This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue((r)), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. RESULTS: On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. CONCLUSION: The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was sensitively detected in the early phase. Further examinations must be performed on muscle injuries of various degrees of severity in order to validate the application of this procedure and to standardise the examination process. PMID- 26556788 TI - [Influence of Ankle Braces on the Prevalence of Ankle Inversion Injuries in the Swiss Volleyball National League A]. AB - BACKGROUND: Ankle inversion is a common injury among volleyball players. The injury rate during a game is 2.1 times higher than during training. As a result, the preventive use of ankle braces is frequently observed in Swiss volleyball leagues. Studies have shown that ankle braces have a preventive effect on the prevalence of ankle inversion. In Switzerland there has been no investigation into the preventive use of braces and their influence on prevalence. For this reason, the goals of this study are 1) to determine when, why and by whom ankle braces are worn and 2) to evaluate the injury rate of users and non-users of ankle braces. SUBJECTS AND METHODS: A modified questionnaire was sent to 18 men's and women's teams of the Swiss National League A. The questionnaire included questions about injury rates and the circumstances of ankle inversion injuries. The data were statistically analysed with Microsoft Excel 2012 and SPSS Version 20. RESULTS: The overall response rate was 61 %, allowing data from 181 players to be analysed. 33 % (59 of 181) of the players used an ankle brace. There was a statistically significant difference in the prevalence of ankle inversion between users (12 injured) and non-users (8 injured) (p = 0.006). Wearing an ankle brace during training or during a game made no difference in the prevention of injuries (p = 0.356). More athletes were injured during training (n = 13) than during a game (n = 7). CONCLUSION: The results of the present study indicate that volleyball players preferably wear ankle braces to prevent injury. More than one third of the players in the study wore an ankle brace, 60 % for primary prevention and 40 % for secondary prevention due to a previous injury. The study shows that significantly more users than non-users of ankle braces were injured. This is contrary to literature. Furthermore it was shown that more injuries occur during training than during a game. This finding results from the fact that ankle braces were rarely worn during training. It is concluded that ankle braces must be worn consistently, especially during training. PMID- 26556789 TI - [Injuries in Freestyle Motocross (FMX): A Retrospective Study]. AB - INTRODUCTION: Freestyle Motocross (FMX) is an emerging extreme sport in which motocross riders perform risky jumps and tricks, which are graded by judges for their degree of difficulty, originality, and style. To this date, injury, patterns and causes in Freestyle Motocross have not been determined. METHODS: Over the time period from January 2006 to December 2012, 19 professional FMX riders of an internationally active FMX team were retrospectively surveyed by means of a questionnaire and questionnaire-based interviews regarding injuries sustained during training, shows, or competition. The questionnaire collected information regarding injury type, circumstances, causes, and treatment. In addition, general information was obtained on body dimensions, experience, training, and equipment used. RESULTS: A total of 54 accidents resulting in 78 severe injuries were registered. The most common types of injuries were fractures (66.6 %), ligament ruptures (7.7 %), and contusions (6.4 %). Most frequently affected body regions were foot/ankle (20.5 %), shoulder (12.8 %), and back (10.3 %). The Backflip was the trick during which most of the injuries occurred (35.2 %). Incorrect execution of jumps (25.9 %) was the leading cause of accidents. CONCLUSION: Based on our data, FMX is a high-risk sport. To avoid injuries, ramps, motorcycles, and equipment should be in the best possible shape and the athletes themselves in good physical and mental condition. Attendance of medical staff during FMX activity is advised at all time. PMID- 26556790 TI - Alone at the Table: Food Behavior and the Loss of Commensality in Widowhood. AB - OBJECTIVES: Eating alone is a known risk factor for nutritional vulnerability in later life. Widowhood often entails loss of commensality (shared meals). This article explores this experience among older widowed women in relation to food behavior. METHOD: Qualitative methods based on constructivist grounded theory were used. Interviews were conducted with 15 women living alone in the community, aged 71 to 86 years, and widowed 6 months to 15 years. RESULTS: Widowhood meant having significantly fewer opportunities for commensality. Participants attributed changes to their food behaviors to the loss of commensality, including food choice, fewer regular meals, and reduced work of meal preparation. These changes were attributed to the experienced difference between shared meals and meals eaten alone, no longer having the commitment of commensality, and having less interest in meal preparation in the absence of obligation or reward of commensality. DISCUSSION: Eating alone symbolized loss and was less enjoyable, yet the pleasure experienced with food was intact. Focusing on the pleasure of eating may help support women when they lose regular commensality late in life. Free from the commitment of commensality, some shifted away from regular meals and simplified their meal preparation strategies. This has implications for clinical and research endeavors. PMID- 26556792 TI - Effects of Common Mycorrhizal Network on Plant Carbohydrates and Soil Properties in Trifoliate Orange-White Clover Association. AB - Common mycorrhizal network (CMN) allows nutrients and signals to pass between two or more plants. In this study, trifoliate orange (Poncirus trifoliata) and white clover (Trifolium repens) were planted in a two-compartmented rootbox, separated by a 37-MUm nylon mesh and then inoculated with an arbuscular mycorrhizal fungus (AMF), Diversispora spurca. Inoculation with D. spurca resulted in formation of a CMN between trifoliate orange and white clover, whilst the best AM colonization occurred in the donor trifoliate orange-receptor white clover association. In the trifoliate orange-white clover association, the mycorrhizal colonization of receptor plant by extraradical hyphae originated from the donor plant significantly increased shoot and root fresh weight and chlorophyll concentration of the receptor plant. Enzymatic activity of soil beta-glucoside hydrolase, protease, acid and neutral phosphatase, water-stable aggregate percentage at 2-4 and 0.5-1 mm size, and mean weight diameter in the rhizosphere of the receptor plant also increased. The hyphae of CMN released more easily-extractable glomalin related soil protein and total glomalin-related soil protein into the receptor rhizosphere, which represented a significantly positive correlation with aggregate stability. AMF inoculation exhibited diverse changes in leaf and root sucrose concentration in the donor plant, and AM colonization by CMN conferred a significant increase of root glucose in the receptor plant. These results suggested that CMN formed in the trifoliate orange-white clover association, and root AM colonization by CMN promoted plant growth, root glucose accumulation, and rhizospheric soil properties in the receptor plant. PMID- 26556791 TI - Post-Prandial Protein Handling: You Are What You Just Ate. AB - BACKGROUND: Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults. OBJECTIVE: To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein. DESIGN: 12 healthy young males ingested 20 g intrinsically [1-13C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-2H5]-phenylalanine, L [ring-2H2]-tyrosine, and L-[1-13C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment. RESULTS: 55.3+/-2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from 291+/-72 to 103+/-66 MUM.min-1.100 mL leg volume-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029+/ 0.002 vs 0.044+/-0.004%.h-1 based upon the muscle protein bound L-[ring-2H5] phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-13C]-phenylalanine into de novo muscle protein (from 0 to 0.0201+/-0.0025 MPE). CONCLUSION: Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis. TRIAL REGISTRATION: trialregister.nl 3638. PMID- 26556793 TI - CONSTANS Controls Floral Repression by Up-Regulating VERNALIZATION2 (VRN-H2) in Barley. AB - In barley (Hordeum vulgare), PHOTOPERIOD1 (Ppd-H1) acts as a major positive regulator of flowering under long-day conditions, while VERNALIZATION2 (VRN-H2) is a strong repressor of flowering under long days before vernalization. By contrast, CONSTANS (CO) plays a key role in the photoperiodic regulation of flowering in Arabidopsis (Arabidopsis thaliana). Here, we study the role of the closest barley CO homologs, HvCO1 and HvCO2, in the long day-dependent control of flowering and their interactions with Ppd-H1 and VRN-H2. HvCO2 overexpression in spring barley, with a natural deletion of the VRN-H2 locus, caused a Ppd-H1 dependent induction of flowering and FLOWERING LOCUS T1 (HvFT1) expression. In winter barley, which carries the VRN-H2 locus, overexpression of HvCO1/CO2 caused an up-regulation of VRN-H2, resulting in a reduced expression of HvFT1 and delayed flowering under long- and short-day conditions. In addition, natural variation at Ppd-H1 altered the expression of VRN-H2 in wild-type plants under long days. VRN-H2, in turn, was involved in the down-regulation of Ppd-H1 and HvCO2, demonstrating strong reciprocal interactions between HvCO2, Ppd-H1, and VRN-H2. Consequently, this study showed that the induction of the floral repressor VRN-H2 and the floral activator HvFT1 was regulated by the same genes, Ppd-H1 and HvCO1/CO2. Our findings provide a novel insight into the photoperiodic regulation of the vernalization pathway in barley. PMID- 26556794 TI - Combining Quantitative Genetics Approaches with Regulatory Network Analysis to Dissect the Complex Metabolism of the Maize Kernel. AB - Metabolic quantitative trait locus (QTL) studies have allowed us to better understand the genetic architecture underlying naturally occurring plant metabolic variance. Here, we use two recombinant inbred line (RIL) populations to dissect the genetic architecture of natural variation of 155 metabolites measured in the mature maize (Zea mays) kernel. Overall, linkage mapping identified 882 metabolic QTLs in both RIL populations across two environments, with an average of 2.1 QTLs per metabolite. A large number of metabolic QTLs (more than 65%) were identified with moderate effects (r(2) = 2.1%-10%), while a small portion (less than 35%) showed major effects (r(2) > 10%). Epistatic interactions between these identified loci were detected for more than 30% of metabolites (with the proportion of phenotypic variance ranging from 1.6% to 37.8%), implying that genetic epistasis is not negligible in determining metabolic variation. In total, 57 QTLs were validated by our previous genome-wide association study on the same metabolites that provided clues for exploring the underlying genes. A gene regulatory network associated with the flavonoid metabolic pathway was constructed based on the transcriptional variations of 28,769 genes in kernels (15 d after pollination) of 368 maize inbred lines. A large number of genes (34 of 58) in this network overlapped with previously defined genes controlled by maize PERICARP COLOR1, while three of them were identified here within QTL intervals for multiple flavonoids. The deeply characterized RIL populations, elucidation of metabolic phenotypes, and identification of candidate genes lay the foundation for maize quality improvement. PMID- 26556795 TI - A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers. AB - A cellulose synthesis complex with a "rosette" shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. This work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self assembly of CESA into a stable trimer in solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. The conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. This study strongly supports the "hexamer of trimers" model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product. PMID- 26556798 TI - Enantioselective Nanoporous Carbon Based on Chiral Ionic Liquids. AB - One of the greatest challenges in modern chemical processing is to achieve enantiospecific control in chemical reactions using chiral media such as chiral mesoporous materials. Herein, we describe a novel and effective synthetic pathway for the preparation of enantioselective nanoporous carbon, based on chiral ionic liquids (CILs). CILs of phenylalanine (CIL(Phe)) are used as precursors for the carbonization of chiral mesoporous carbon. We employ circular dichroism spectroscopy, isothermal titration calorimetry (ITC), and chronoamperometry in order to demonstrate the chiral nature of the mesoporous carbon. The approach presented in this paper is highly significant for the development of a new type of chiral porous materials for enantioselective chemistry. In addition, it contributes significantly to our understanding of the structure and nature of chiral nanoporous materials and surfaces. PMID- 26556796 TI - ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) Interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) Linking Iron Deficiency and Oxidative Stress Responses. AB - Plants grown under iron (Fe)-deficient conditions induce a set of genes that enhance the efficiency of Fe uptake by the roots. In Arabidopsis (Arabidopsis thaliana), the central regulator of this response is the basic helix-loop-helix transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT). FIT activity is regulated by protein-protein interactions, which also serve to integrate external signals that stimulate and possibly inhibit Fe uptake. In the search of signaling components regulating FIT function, we identified ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12), an abiotic stress-induced transcription factor. ZAT12 interacted with FIT, dependent on the presence of the ethylene responsive element-binding factor-associated amphiphilic repression motif. ZAT12 protein was found expressed in the root early differentiation zone, where its abundance was modulated in a root layer-specific manner. In the absence of ZAT12, FIT expression was upregulated, suggesting a negative effect of ZAT12 on Fe uptake. Consistently, zat12 loss-of-function mutants had higher Fe content than the wild type at sufficient Fe. We found that under Fe deficiency, hydrogen peroxide (H2O2) levels were enhanced in a FIT-dependent manner. FIT protein, in turn, was stabilized by H2O2 but only in the presence of ZAT12, showing that H2O2 serves as a signal for Fe deficiency responses. We propose that oxidative stress induced ZAT12 functions as a negative regulator of Fe acquisition. A model where H2O2 mediates the negative regulation of plant responses to prolonged stress might be applicable to a variety of stress conditions. PMID- 26556797 TI - Inhibitory Effect of Epigallocatechin Gallate on the Virulence of Clostridium difficile PCR Ribotype 027. AB - Clostridium difficile infection (CDI) is the most prevalent cause of health-care associated infections. CDI-related health-care costs and deaths are both increasing annually on a global scale. C. difficile have been reported in food products in Canada, Europe, and the United States; however, the systematic transmission of C. difficile between humans and animals is yet to be understood. Because of the limitations of current therapeutic options, there is a need for the development of new patient treatments. Epigallocatechin gallate (EGCG) is a major catechin compound found in green tea extracts and exhibits antioxidant and antimicrobial activities. This study was conducted to investigate the inhibitory effects of EGCG on the expression of virulence genes in C. difficile and in C. difficile-associated diseases by inhibition of quorum sensing. The protein expression of autoinducer-2 (AI-2) was evaluated by AI-2 activity. EGCG at various concentrations had an inhibitory effect on AI-2 production, especially at 10 MUg/mL. EGCG also significantly repressed the transcription of virulence genes, including luxS and tcdA, and prolonged the survival of Caenorhabditis elegans infected with C. difficile. Furthermore, treatment with EGCG effectively protected C. difficile-infected mice from C. difficile-induced death. Histological analysis of the colon and cecum of these mice revealed that EGCG protected tissues of the lower intestinal tract from damage. EGCG exerted growth inhibitory and bactericidal activities on C. difficile in C. difficile-infected mice. Our results suggest that EGCG has significant antipathogenic effects on C. difficile and can be used to prevent or treat C. difficile-associated diseases or C. difficile infections. PMID- 26556799 TI - Concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma. AB - A 10-year-old girl with a family history of Hodgkin's lymphoma presented with a 2 month history of cervical lymphadenopathy and weight loss. Biopsy indicated concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma. Such an association is rare, especially so in children, but is not an isolated phenomenon, thereby prompting the question of whether Langerhans cell histiocytosis is a reactive or a neoplastic process. PMID- 26556801 TI - Editorial: Synovitis and Pain Sensitization. PMID- 26556800 TI - A Diversity of Conserved and Novel Ovarian MicroRNAs in the Speckled Wood (Pararge aegeria). AB - microRNAs (miRNAs) are important regulators of animal development and other processes, and impart robustness to living systems through post-transcriptional regulation of specific mRNA transcripts. It is postulated that newly emergent miRNAs are generally expressed at low levels and with spatiotemporally restricted expression domains, thus minimising effects of spurious targeting on animal transcriptomes. Here we present ovarian miRNA transcriptome data for two geographically distinct populations of the Speckled Wood butterfly (Pararge aegeria). A total of 74 miRNAs were identified, including 11 newly discovered and evolutionarily-young miRNAs, bringing the total of miRNA genes known from P. aegeria up to 150. We find a positive correlation between miRNA age and expression level. A common set of 55 miRNAs are expressed in both populations. From this set, we identify seven that are consistently either ovary-specific or highly upregulated in ovaries relative to other tissues. This 'ovary set' includes miRNAs with known contributions to ovarian function in other insect species with similar ovaries and mode of oogenesis, including miR-989 and miR 2763, plus new candidates for ovarian function. We also note that conserved miRNAs are overrepresented in the ovary relative to the whole body. PMID- 26556802 TI - Sperm Proteome Maturation in the Mouse Epididymis. AB - In mammals, transit through the epididymis, which involves the acquisition, loss and modification of proteins, is required to confer motility and fertilization competency to sperm. The overall dynamics of maturation is poorly understood, and a systems level understanding of the complex maturation process will provide valuable new information about changes occurring during epididymal transport. We report the proteomes of sperm collected from the caput, corpus and cauda segments of the mouse epididymis, identifying 1536, 1720 and 1234 proteins respectively. This study identified 765 proteins that are present in sperm obtained from all three segments. We identified 1766 proteins that are potentially added (732) or removed (1034) from sperm during epididymal transit. Phenotypic analyses of the caput, corpus and cauda sperm proteomes identified 60 proteins that have known sperm phenotypes when mutated, or absent from sperm. Our analysis indicates that as much as one-third of proteins with known sperm phenotypes are added to sperm during epididymal transit. GO analyses revealed that cauda sperm are enriched for specific functions including sperm-egg recognition and motility, consistent with the observation that sperm acquire motility and fertilization competency during transit through the epididymis. In addition, GO analyses revealed that the immunity protein profile of sperm changes during sperm maturation. Finally, we identified components of the 26S proteasome, the immunoproteasome, and a proteasome activator in mature sperm. PMID- 26556803 TI - Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases. AB - Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups-probands with SAID, their unaffected twins, and matched, unrelated healthy controls-using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID. PMID- 26556804 TI - Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study. AB - BACKGROUND AND AIMS: Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX. METHODS AND RESULTS: Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 +/- 7.8 vs 32.7 +/- 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3) mg/dL, and 5.8 (5.4-7.6)] MUg/L, respectively), while urinary cGMP was reduced [270 (250-355) vs 581 (437-698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up. CONCLUSIONS: Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time. PMID- 26556805 TI - Preclinical Bioassay of a Polypropylene Mesh for Hernia Repair Pretreated with Antibacterial Solutions of Chlorhexidine and Allicin: An In Vivo Study. AB - INTRODUCTION: Prosthetic mesh infection constitutes one of the major complications following hernia repair. Antimicrobial, non-antibiotic biomaterials have the potential to reduce bacterial adhesion to the mesh surface and adjacent tissues while avoiding the development of novel antibiotic resistance. This study assesses the efficacy of presoaking reticular polypropylene meshes in chlorhexidine or a chlorhexidine and allicin combination (a natural antibacterial agent) for preventing bacterial infection in a short-time hernia-repair rabbit model. METHODS: Partial hernia defects (5 x 2 cm) were created on the lateral right side of the abdominal wall of New Zealand White rabbits (n = 21). The defects were inoculated with 0.5 mL of a 106 CFU/mL Staphylococcus aureus ATCC25923 strain and repaired with a DualMesh Plus antimicrobial mesh or a Surgipro mesh presoaked in either chlorhexidine (0.05%) or allicin-chlorhexidine (900 MUg/mL-0.05%). Fourteen days post-implant, mesh contraction was measured and tissue specimens were harvested to evaluate bacterial adhesion to the implant surface (via sonication, S. aureus immunolabeling), host-tissue incorporation (via staining, scanning electron microscopy) and macrophage response (via RAM-11 immunolabeling). RESULTS: The polypropylene mesh showed improved tissue integration relative to the DualMesh Plus. Both the DualMesh Plus and the chlorhexidine-soaked polypropylene meshes exhibited high bacterial clearance, with the latter material showing lower bacterial yields. The implants from the allicin-chlorhexidine group displayed a neoformed tissue containing differently sized abscesses and living bacteria, as well as a diminished macrophage response. The allicin-chlorhexidine coated implants exhibited the highest contraction. CONCLUSIONS: The presoaking of reticular polypropylene materials with a low concentration of chlorhexidine provides the mesh with antibacterial activity without disrupting tissue integration. Due to the similarities found with the antimicrobial DualMesh Plus material, the chlorhexidine concentration tested could be utilized as a prophylactic treatment to resist infection by prosthetic mesh during hernia repair. PMID- 26556806 TI - Novel Pathways Revealed in Bursa of Fabricius Transcriptome in Response to Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) has major negative impacts on human and animal health. Recent research suggests food-borne links between human and animal ExPEC diseases with particular concern for poultry contaminated with avian pathogenic E. coli (APEC), the avian ExPEC. APEC is also a very important animal pathogen, causing colibacillosis, one of the world's most widespread bacterial diseases of poultry. Previous studies showed marked atrophy and lymphocytes depletion in the bursa during APEC infection. Thus, a more comprehensive understanding of the avian bursa response to APEC infection will facilitate genetic selection for disease resistance. Four-week-old commercial male broiler chickens were infected with APEC O1 or given saline as a control. Bursas were collected at 1 and 5 days post-infection (dpi). Based on lesion scores of liver, pericardium and air sacs, infected birds were classified as having mild or severe pathology, representing resistant and susceptible phenotypes, respectively. Twenty-two individual bursa RNA libraries were sequenced, each yielding an average of 27 million single-end, 100-bp reads. There were 2469 novel genes in the total of 16,603 detected. Large numbers of significantly differentially expressed (DE) genes were detected when comparing susceptible and resistant birds at 5 dpi, susceptible and non-infected birds at 5 dpi, and susceptible birds at 5 dpi and 1 dpi. The DE genes were associated with signal transduction, the immune response, cell growth and cell death pathways. These data provide considerable insight into potential mechanisms of resistance to ExPEC infection, thus paving the way to develop strategies for ExPEC prevention and treatment, as well as enhancing innate resistance by genetic selection in animals. PMID- 26556807 TI - The Encoding of Decision Difficulty and Movement Time in the Primate Premotor Cortex. AB - Estimating the difficulty of a decision is a fundamental process to elaborate complex and adaptive behaviour. In this paper, we show that the movement time of behaving monkeys performing a decision-making task is correlated with decision difficulty and that the activity of a population of neurons in ventral Premotor cortex correlates with the movement time. Moreover, we found another population of neurons that encodes the discriminability of the stimulus, thereby supplying another source of information about the difficulty of the decision. The activity of neurons encoding the difficulty can be produced by very different computations. Therefore, we show that decision difficulty can be encoded through three different mechanisms: 1. Switch time coding, 2. rate coding and 3. binary coding. This rich representation reflects the basis of different functional aspects of difficulty in the making of a decision and the possible role of difficulty estimation in complex decision scenarios. PMID- 26556809 TI - Brevibacillus sediminis sp. nov., isolated from a hot spring. AB - Strain YIM 78300T, a novel Gram-stain-positive, moderately thermophilic, endospore-forming, rod-shaped, motile bacterium, was recovered from the sediment of a hot spring in the Tagejia Geothermal Field, Angren, Tibet province, western China. Optimum growth was observed at 50-55 degrees C, at pH 7.0 and with 0-1.5 % (w/v) NaCl. Phylogenetic analysis of the 16S rRNA gene sequence of strain YIM 78300T indicated that it belongs to the genus Brevibacillus. Similarity levels between the 16S rRNA gene sequences of the new isolate and those of the type strains of Brevibacillus members were 96.9-96.3 %; highest sequence similarity was with Brevibacillus thermoruber DSM 7064T. The predominant menaquinone was MK 7 and the major cellular fatty acids were iso-C15 : 0 and iso-C17 : 0. The major polar lipids were phosphatidyl-N-methylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified phospholipids, an unidentified aminophospholipid and two unidentified polar lipids. The G+C content of the genomic DNA of strain YIM 78300T was 57.9 mol%. Based on phylogenetic analyses, and physiological and biochemical characteristics, strain YIM 78300T is considered to represent a novel species of the genus Brevibacillus, for which the name Brevibacillus sediminis sp. nov. is proposed. The type strain is YIM 78300T ( = DSM 29928T = CPCC 100738T). PMID- 26556810 TI - [Not Available]. PMID- 26556811 TI - Late Vitamin K Deficient Bleeding in 2 Young Infants--Renaissance of a Preventable Disease. AB - INTRODUCTION: Late vitamin K deficiency bleeding in young infants is a rare disorder which occurs almost exclusively in breast-fed infants who did not receive proper vitamin K prophylaxis at birth and who might additionally suffer from cholestasis. Its impact on morbidity is high since in 50% of the cases it presents with intracranial hemorrhage with a mortality rate of 20% and life-long neurologic sequelae in 30% of the affected infants. CASE REPORTS: 2 male infants were both admitted to our unit at the age of 5 weeks with subdural hematoma with midline shift due to late vitamin K deficiency bleeding. Both infants did not receive the recommended Vitamin K prophylaxis in Germany. One patient presented with cholestatic jaundice on admission as an additional risk factor. DISCUSSION: Parents who in the apparent best interest for their children refuse the recommended and well established vitamin K prophylaxis at birth leading to the reappearance of late vitamin K deficiency bleeding. These parents also tend to refuse routine immunizations of childhood in later life, which not only have an impact on their own child but might bear a risk for the whole community. CONCLUSION: It is the responsibility of health-care takers to show increased awareness to the growing number of parents refusing vitamin K prophylaxis at birth and educate them properly about the devastating consequences of late vitamin K deficiency bleeding. PMID- 26556813 TI - Acting on incidental findings in research imaging. PMID- 26556812 TI - Clinical and molecular study in a long-surviving patient with MLASA syndrome due to novel PUS1 mutations. AB - Myopathy-lactic acidosis-sideroblastic anemia (MLASA) syndrome is a rare autosomal recessive disease. We studied a 43-year-old female presenting since childhood with mild cognitive impairment and sideroblastic anemia. She later developed hepatopathy, cardiomyopathy, and insulin-dependent diabetes. Muscle weakness appeared in adolescence and, at age 43, she was unable to walk. Two novel different mutations in the PUS1 gene were identified: c.487delA (p.I163Lfs*4) and c.884 G>A (p.R295Q). Quantitative analysis of DNA from skeletal muscle biopsies showed a significant increase in mitochondrial DNA (mtDNA) content in the patient compared to controls. Clinical and molecular findings of this patient widen the genotype-phenotype spectrum in MLASA syndrome. PMID- 26556814 TI - Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression. AB - : This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences. IN CONCLUSION: IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing. PMID- 26556815 TI - Successes of SPRINT, but Still Some Hurdles to Cross. PMID- 26556816 TI - Monashia flava gen. nov., sp. nov., an actinobacterium of the family Intrasporangiaceae. AB - A novel actinobacterial strain, MUSC 78T, was isolated from a mangrove soil collected from Peninsular Malaysia. The taxonomic status of this strain was determined using a polyphasic approach. Comparative 16S rRNA gene sequence analysis revealed that strain MUSC 78T represented a novel lineage within the class Actinobacteria. Strain MUSC 78T formed a distinct clade in the family Intrasporangiaceae and was related most closely to members of the genera Terrabacter (98.3-96.8 % 16S rRNA gene sequence similarity), Intrasporangium (98.2-96.8 %), Humibacillus (97.2 %), Janibacter (97.0-95.3 %), Terracoccus (96.8 %), Kribbia (96.6 %), Phycicoccus (96.2-94.7 %), Knoellia (96.1-94.8 %), Tetrasphaera (96.0-94.9 %) and Lapillicoccus (95.9 %). Cells were irregular rod shaped or cocci and stained Gram-positive. The cell-wall peptidoglycan type was A3gamma, with ll-diaminopimelic acid as the diagnostic diamino acid. The main cell-wall sugar was mannose and lower amounts of galactose and rhamnose were present. The predominant menaquinone was MK-8(H4). The polar lipid profile consisted of phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol and phosphoglycolipid. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0. The DNA G+C content was 73.1 mol%. Based on this polyphasic study, MUSC 78T exhibited phylogenetic and phenotypic differences from members of the genera of the family Intrasporangiaceae, and therefore a novel species of a new genus, Monashia flava gen. nov., sp. nov., is proposed. The type strain of Monashia flava is MUSC 78T ( = DSM 29621T = MCCC 1K00454T = NBRC 110749T). PMID- 26556817 TI - Intensive blood pressure control reduces cardiovascular events, studies show. PMID- 26556818 TI - Flavitalea soli sp. nov. isolated from soil. AB - A Gram-stain-negative, rod-shaped, non-flagellated, mesophilic, yellow-pigmented, aerobic bacterium, designated strain KIS20-3T, was isolated from a soil sample of Baengnyeong Island in Onjin county, Republic of Korea. According to 16S rRNA gene sequence analysis, the isolate showed highest similarities with Flavitalea populi HY-50RT (94.5 %), Niastella populi THYL-44T (94.2 %) and Flavitalea gansuensis JCN-23T (93.7 %). The neighbour-joining tree based on 16S rRNA gene sequences showed that strain KIS20-3T formed a subcluster with members of the genus Flavitalea, and this subcluster was closely related to members of the genera Niastella, Segetibacter and Parasegetibacter within the family Chitinophagaceae. The major fatty acids of strain KIS20-3T were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G, and the predominant isoprenoid quinone was menaquinone 7. The polar lipid profile comprised large amounts of phosphatidylethanolamine and one unknown polar lipid, and moderate or small amounts of four unknown aminophospholipids, two unknown aminolipids, three unknown lipids and one unknown phospholipid. The G+C content of the DNA of strain KIS20-3T was 55.7 mol%. On the basis of the results of the polyphasic characterization presented in this study, it is concluded that strain KIS20-3T represents a novel species of the genus Flavitalea, for which the name Flavitalea soli sp. nov. is proposed. The type strain is KIS20-3T ( = KACC 17319T = JCM 19937T). PMID- 26556819 TI - Sentinel lymph node biopsy in melanoma. PMID- 26556820 TI - General practice commissioning: in whose interests? PMID- 26556821 TI - Sex Differences in the Presentation, Care, and Outcomes of Transient Ischemic Attack: Results From the Ontario Stroke Registry. AB - BACKGROUND AND PURPOSE: Little is known about whether sex differences exist in the presentation, management, and outcomes of transient ischemic attack. METHODS: We conducted a cohort study of 5991 consecutive patients with transient ischemic attack admitted to 11 stroke centers in Ontario, Canada, between July 1, 2003, and March 31, 2008 and compared presenting symptoms, processes of care, and outcomes in women and men. We used linkages to administrative databases to evaluate mortality and recurrent vascular events within 30 days and 1 year of the initial presentation, with multivariable analyses to assess whether sex differences persisted after adjustment for age and comorbid conditions. RESULTS: The most common presenting symptoms for both sexes were weakness, speech impairment, and sensory deficit, with headache being slightly more frequent in women. Women were less likely than men to undergo carotid imaging, carotid endarterectomy, or receive lipid-lowering therapy. One-year mortality was slightly lower in women than in men (adjusted hazard ratio, 0.77; 95% confidence interval, 0.63-0.94). CONCLUSIONS: We found only minor sex differences in the presentation and management of transient ischemic attack, suggesting that current public awareness campaigns focusing on classic warning signs are appropriate for both women and men. Future work should focus on evaluating whether lower rates of carotid imaging, endarterectomy, and lipid-lowering therapy in women reflect undertreatment of women or are appropriate based on patient eligibility. PMID- 26556822 TI - Plasma d-Dimer and Incident Ischemic Stroke and Coronary Heart Disease: The Atherosclerosis Risk in Communities Study. AB - BACKGROUND AND PURPOSE: Epidemiological studies have documented that plasma d dimer, a fibrin degradation product, is a risk marker for coronary heart disease, but there is limited prospective evidence for stroke. Given that thrombosis is a key mechanism for many strokes, we studied whether d-dimer is a risk marker for ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: We measured d-dimer in 11 415 ARIC participants free of stroke and coronary heart disease in 1992 to 1995. We followed them for stroke, stroke subtype, and coronary heart disease events through 2012. RESULTS: Over a median of 18 years of follow-up, 719 participants had incident strokes (628 ischemic and 91 hemorrhagic). d-dimer was associated positively with risk of total, ischemic, and cardioembolic strokes, with risk elevated primarily for the highest quintile of d-dimer. After adjustment for other cardiovascular risk factors, the hazard ratio for the highest versus lowest quintile of d-dimer was 1.30 (95% confidence interval, 1.02-1.67) for total stroke, 1.33 (95% confidence interval, 1.02-1.73) for ischemic stroke, and 1.79 (95% confidence interval, 1.08-2.95) for cardioembolic stroke. There was no association with hemorrhagic, lacunar, or nonlacunar stroke categories. d-dimer was positively but weakly associated with coronary heart disease incidence. CONCLUSIONS: A higher basal plasma d-dimer concentration in the general population is a risk marker for ischemic stroke, especially cardioembolic stroke. PMID- 26556823 TI - Predictors of Stroke After Transient Ischemic Attack in Children. AB - BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) in children has received far less attention compared with TIA in adults. The risk factors of stroke after TIA in children are relatively unknown. We aimed to determine the percentage of children who have stroke after TIA and the risk factors associated with stroke after TIA. METHODS: We searched the medical records at Boston Children's Hospital for the year 2010 to find children who were evaluated for TIA to determine associated risk factors of stroke after TIA. We included children who were evaluated in 2009 through 2010 for TIA and had magnetic resonance imaging. We examined follow-up imaging through August 2014 for subsequent stroke. Logistic regression was used to calculate odds ratios for factors in our cohort who are associated with stroke after presentation with TIA. RESULTS: We identified 63 children who experienced a TIA. The mean time of imaging follow-up was 4.5 years after TIA presentation. Of the 63 children, 10 (16%) developed radiological evidence of ischemic cerebral injury within the follow-up period. Four of the 10 (6%) demonstrated diffusion abnormalities on magnetic resonance imaging at TIA presentation, whereas 8 (13%) had a stroke after their TIA. Arteriopathy, female sex, and autoimmune disorders were significantly associated with stroke after TIA. CONCLUSIONS: In our cohort of children, stroke occurred after TIA at a rate similar to that seen in adults, but the risk factors for stroke after TIA in children are different. PMID- 26556825 TI - Impact of Leukoaraiosis Burden on Hemispheric Lateralization of the National Institutes of Health Stroke Scale Deficit in Acute Ischemic Stroke. AB - BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) awards higher deficit scores for infarcts in the dominant hemisphere when compared with otherwise similar infarcts in the nondominant hemisphere. This has been shown to adversely affect stroke recognition, therapeutic decisions, and outcome. However, factors modifying the association between infarct side and deficit severity are incompletely understood. Thus, we sought to determine whether age and age-related leukoaraiosis alter the relation between NIHSS deficit score and the side and volume of infarction. METHODS: We studied 238 patients with supratentorial, nonlacunar ischemic infarcts prospectively included in our stroke registry between January 2013 and January 2014. NIHSS deficit severity was assessed at the time of presentation. Infarct volumes were assessed by manual planimetry on diffusion-weighted imaging. Leukoaraiosis burden was graded on fluid-attenuated inversion recovery images according to the Fazekas scale and dichotomized to none-to-mild (0-2) versus severe (3-6). Multivariable linear regression with backward elimination was used to identify independent predictors of the admission NIHSS. RESULTS: Left-hemispheric infarction (P<0.001), severe leukoaraiosis (P=0.001), their interaction term (P=0.005), infarct volume (P<0.001), and sex (P=0.013) were independently associated with the NIHSS deficit. Analysis of the individual NIHSS components showed that severe leukoaraiosis was associated with an increase of the lateralizing components of the NIHSS in patients with right-hemispheric infarction (P<0.05). CONCLUSIONS: Severe leukoaraiosis substantially attenuates the classic hemispheric lateralization of the NIHSS deficit by relating to greater NIHSS scores of components that are typically assigned to left hemisphere function. PMID- 26556824 TI - Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study. AB - BACKGROUND AND PURPOSE: Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. METHODS: The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. RESULTS: Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12% 48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection. CONCLUSIONS: Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed. PMID- 26556826 TI - Estimating Weight of Patients With Acute Stroke When Dosing for Thrombolysis. AB - BACKGROUND AND PURPOSE: Estimating patient weight forms an important part of emergency ischemic stroke management guiding the dose of alteplase (tissue-type plasminogen activator). Weighing patients with stroke can be logistically challenging and time consuming, potentially delaying treatment times. We aimed to assess the reliability of approximating weight to determine recombinant tissue type plasminogen activator dose and whether potential inaccurate dosing affected patient outcomes. METHODS: Two hundred forty-two consecutive patients were studied at a large tertiary stroke center. Estimated and actual measured weight, alteplase dose, and pre-and post-modified Rankin Scale/National Institute of Health Stroke Scale outcome were recorded for each patient. RESULTS: Clinicians significantly underestimated weights by 1.13 kg (range, -43 to +18 kg; SD, 7.14; P<0.05). The difference between estimated and actual weight proved to be greatest in the heaviest third of patients (-4.51 kg; SD, 8.35; P<0.001), resulting in 19.7% of patients receiving a deviation of at least 10% from the recommended recombinant tissue-type plasminogen activator dose. On average, the heaviest third of patients received an underdose of 0.04 mg/kg and were found to have a greater baseline National Institute of Health Stroke Scale on admission (P<0.001). National Institute of Health Stroke Scale improvement by day 7 or on discharge was significantly reduced in patients weighing >78 kg (National Institute of Health Stroke Scale score difference of 4.0 points, P<0.05) than in lighter individuals. CONCLUSIONS: Clinicians are poor at approximating the weights of patients with stroke in the acute setting, especially when patients lie at the extremes of weight. Beds capable of weighing patients should be mandated in emergency rooms for patients with acute stroke. PMID- 26556827 TI - Former Duke University oncologist is guilty of research misconduct, US officials find. PMID- 26556828 TI - India's HIV prevention programme is running out of condoms. PMID- 26556830 TI - Delivery of an Ebola Virus-Positive Stillborn Infant in a Rural Community Health Center, Sierra Leone, 2015. AB - We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women in an Ebola setting. PMID- 26556831 TI - Validation of a Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Schistosoma mansoni Diagnosis in the Sahel, and Potential Cross-Reaction in Pregnancy. AB - On the shores of Lake Chad, schistosomiasis among mobile pastoralists was investigated in a field laboratory. Point-of-care circulating cathodic antigen (POC-CCA) cassette test, reagent strip, and filtration were conducted on urine samples. Fresh stool samples were subjected to the Kato-Katz technique, and fixed samples were examined with an ether-concentration method at a reference laboratory. POC-CCA urine cassette tests revealed a Schistosoma mansoni prevalence of 6.9%, compared with only 0.5% by stool microscopy. Three pregnant women with otherwise negative urine and stool testing had positive POC-CCA. This observation raises concern of cross-reactivity in pregnancy. Hence, two pregnant women in Switzerland with no history of schistosomiasis were subjected to POC-CCA and one tested positive. Our data suggest that POC-CCA can be performed under extreme Sahelian conditions (e.g., temperatures > 40 degrees C), and it is more sensitive than stool microscopy for S. mansoni diagnosis. However, potential cross-reactivity in pregnancy needs further investigation. PMID- 26556829 TI - ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie Tooth disease. AB - Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ~ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot-Marie-Tooth disease type 2H on chromosome 8q13-21.1 was excluded by linkage analysis. Pedigrees originated in Italy, Brazil, Canada, England, Iran, and Japan. Interestingly, we identified 15 ALS5/SPG11/KIAA1840 mutations in 12 families (two sequence variants were never reported before, p.Gln198* and p.Pro2212fs*5). No large deletions/duplications were detected in these patients. The novel mutations seemed to be pathogenic since they co segregated with the disease in all pedigrees and were absent in 300 unrelated controls. Furthermore, in silico analysis predicted their pathogenic effect. Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including autosomal recessive axonal Charcot-Marie Tooth disease. PMID- 26556832 TI - Changing Dynamics of Human-Rickettsial Interactions. PMID- 26556833 TI - Primary Giant Splenic Echinococcal Cyst Treated by Laparoscopy. AB - Cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. Liver and lungs are the most commonly affected organs whereas splenic infection is rarer and its primary involvement occurs in less than 2% of abdominal CE. We report a case of primary giant splenic hydatid cyst in a 75-year-old Peruvian woman that was laparoscopically removed without any complications, perioperative prophylactic chemotherapy with albendazole 400 mg twice a day 5 days before, and 7 days after the surgical procedure was administered, postoperative recovery was uneventful, and; at her 3-month follow up the patient remains asymptomatic and an abdominal computed tomography scan demonstrated a cystic cavity of 15 cm diameter with no daughter vesicles, neither other abdominal organ involvement. This case is in line with the existing literature on laparoscopical treatment of splenic cystic hydatid disease, suggesting that laparoscopical treatment is a safe and effective approach for large splenic hydatid cysts to be preferred to open surgical techniques. PMID- 26556834 TI - Polymerase Chain Reaction in the Diagnosis of Visceral Leishmaniasis Recurrence in the Setting of Negative Splenic Smears. AB - This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence. PMID- 26556835 TI - The microwave syndrome or electro-hypersensitivity: historical background. AB - Microwave generating equipment first became common during World War 2 with the development of radar. Soviet bloc countries reported that individuals exposed to microwaves frequently developed headaches, fatigue, loss of appetite, sleepiness, difficulty in concentration, poor memory, emotional instability, and labile cardiovascular function, and established stringent exposure standards. For a variety of reasons these reports were discounted in Western countries, where the prevailing belief was that there could be no adverse health effects of electromagnetic fields (EMFs) that were not mediated by tissue heating. The reported Soviet effects were at lower intensities than those that cause heating. However, there were several accidental exposures of radar operators in Western countries that resulted in persistent symptoms similar to those described above. The Soviets irradiated the US Embassy in Moscow with microwaves during the period 1953-1975, and while no convincing evidence of elevated cancer rates was reported, there were reports of "microwave illness". Officials passed these complaints off as being due to anxiety, not effects of the microwave exposure. There is increasing evidence that the "microwave syndrome" or "electro hypersensitivity" (EHS) is a real disease that is caused by exposure to EMFs, especially those in the microwave range. The reported incidence of the syndrome is increasing along with increasing exposure to EMFs from electricity, WiFi, mobile phones and towers, smart meters and many other wireless devices. Why some individuals are more sensitive is unclear. While most individuals who report having EHS do not have a specific history of an acute exposure, excessive exposure to EMFs, even for a brief period of time, can induce the syndrome. PMID- 26556836 TI - Normal weight obesity among young adults in Trinidad and Tobago: prevalence and associated factors. AB - BACKGROUND: Patients with normal weight obesity (NWO) have a normal body mass index (BMI) but elevated body fat percentage (BF%), thereby increasing their risk of cardiovascular and metabolic disorders. The purpose of this research was to determine the prevalence of NWO and its associated factors in a sample of young adults in Trinidad and Tobago (T&T). METHODS: A cross sectional study involving a convenience non-voluntary sample of participants with a normal BMI of 18.5-24.9 kg/m2 was conducted. The following information was collected: history, basic anthropometric measurements, including BF% via the Tanita Ironman Body Composition Analyzer (BC554), physical examination and basic blood investigations. Participants were divided into two groups; normal BF% (<23.1% males, <33.3% females) and elevated BF% (>=23.1% males, >=33.3% females). RESULTS: Two hundred and thirty-six students participated, F:M (2.1:1), aged 18 28 years [Mean 21.33 (SD 2.5)], mean BMI 21.66 (SD 1.9). A response rate of 80.3%. The prevalence of NWO for this population was 19.9% [95% confidence interval (CI) 15.1-25.7]. Males 14.4% (95% CI 10.3-19.7) and females 5.5% (95% CI 3.1-9.5). Variables with a statistically significant association with NWO included gender, waist circumference, waist-to-hip ratio (WHR), systolic blood pressure (BP), the ratio of total cholesterol (TC) to high density lipoprotein and in females, the presence of polycystic ovarian syndrome (PCOS) (p<0.05). Binary logistic regression revealed that predictors of NWO were male gender and waist circumference. CONCLUSIONS: One in five of this young adult population was found to have NWO. Long-term studies are recommended to study the full implications of these findings. PMID- 26556837 TI - Health seeking behaviour and health awareness among rural and urban adolescents in Dehradun District, Uttarakhand, India. AB - BACKGROUND: Adolescents constituted 19% population of India in 2011. Adolescents have health seeking behaviour different from that of adults. We estimated the utilisation of available health care services by adolescents and awareness regarding various health issues in the urban and rural Dehradun District, Uttarakhand, India. We also described knowledge and practices of public sector health care providers. METHODOLOGY: We conducted a cross-sectional survey among adolescents 10-19 years in the urban Dehradun and rural Chakrata block of the Dehradun District. We used cluster sampling with sample size 680 each in urban and rural areas. We collected data from adolescents using semi structured questionnaire on health awareness and utilisation of health care services. Public sector health care providers were surveyed about their knowledge and practices regarding adolescents health. RESULTS: We surveyed 1463 adolescents. The overall mean age was 14.4 (2.6) years, about half being females. Half of the adolescents who had any illness used the public sector. Awareness about anaemia was 48% in urban and 12% in rural areas. A higher proportion of females (Rural: 89%, Urban: 76%) were aware of condoms as contraceptives than males (Rural: 68%, Urban: 12%). Only 62% of doctors and 49% of paramedical staff had knowledge regarding services under Adolescents Reproductive and Sexual Health (ARSH). CONCLUSION: Awareness regarding various health issues was low among males as compared to females, especially in rural areas. School based health promotion programs should be carried out to increase awareness among adolescents. Health facilities should be strengthened to provide adolescent friendly health services to enhance utilisation. PMID- 26556838 TI - Tubo-ovarian abscess in non sexually active adolescents. AB - A tubo-ovarian abscess is a rare presentation in non-sexually active adolescents; only 11 cases have been reported in the literature. Variable approaches for diagnosis and management are described. We present a 19-year-old, non-sexually active, medically free girl, who had an abdominopelvic mass with abdominal pain and vomiting followed by fever. She had a confusing presentation of malignancy versus tuberculosis, with the help of imaging, diagnosis and treatment with percutaneous drainage, conservative treatment was achieved. Diagnosis of a tubo ovarian abscess is difficult in non-sexually active adolescents, a high clinical index of suspicion is important as misdiagnosis may lead to radical and aggressive management, conservative management is possible in many of these patients. PMID- 26556839 TI - Prevalence and correlates of suicidal ideation and attempts among children and adolescents. AB - Suicide is a potentially preventable public health issue. It is therefore important to examine its immediate precursors, including suicidal ideation and attempts, to help in the development of future public health interventions. The present study reports the prevalence of suicidal ideation and attempts in the past 12 months in children and adolescents and identifies correlates of such behaviors in a large and diverse sample of middle and high school students. Data were drawn from a representative sample of Ottawa students (n=1922) aged 11-20 years (14.4+/-1.9 years) from three cycles (2009, 2011 and 2013) of the Ontario Student Drug Use and Health Survey (OSDUHS), a cross-sectional school-based appraisal of students in grades 7-12 across Ontario, Canada. Overall, 10.8% of students exhibited suicidal ideation and 3.0% reported suicide attempts in the past 12 months. The conditional probability of making an attempt was 25.5% among suicide ideators. Multivariable analyses indicated that being a girl and using alcohol and cannabis were positively associated with suicidal ideation, while tobacco was positively associated with suicide attempts. Being a victim of school bullying was significantly associated with reports of suicidal ideation and attempts, whereas school connectedness had protective effects against both suicidal ideation and attempts. These results indicate that suicidal ideation and attempts are related to other risky behaviors. Suicide-prevention efforts should be integrated within broader health-promoting initiatives. PMID- 26556840 TI - Prevalence of stress and stress tolerance levels among adolescent boys - a district level cross sectional study in South India. AB - BACKGROUND: Adolescence is a tumultuous period of hormonal and psychological transitions ranging from 10 to 19 years (WHO). This growth phase is usually accompanied by stressors. Very few studies have reported the prevalence of stress levels among adolescent boys. Our aim was to assess the prevalence and determinants of stress and its tolerance levels among high school boys. METHODS: A cross sectional study design was selected for this purpose. A standardized self reported questionnaire was administered to 1153 high school boys. A score of 130 and more was used to classify the participants as stressed. RESULTS: The prevalence of stress and its tolerance levels was found to be 55% and 33.7%, respectively. Also correlations suggest that parental education and occupational status play a significant role in adolescent stress. Together, these findings suggest necessitating an intervention to counter the same. CONCLUSION: The proportion of stressed adolescent boys (55.5%) reported to have poor stress tolerance (41%). Studies addressing stress among high school adolescents remain unexplored. The basic determinants of stress are not researched upon these age groups. Our study reports the prevalence of stress to be 55% among high school boys. This could be the fundamental basis of designing suitable stress management programs for adolescents that could reduce their stress levels. PMID- 26556841 TI - Differences in use of contraception by age, sex and HIV status of 10-19-year-old adolescents in Nigeria. AB - OBJECTIVE: The study tried to identify predictors of good knowledge of contraceptive methods and use of condoms at the last sexual act with a girl/boyfriend by adolescents aged 10-19 years in Nigeria. It also tried to find the association between age, sex and HIV status with the study outcomes. METHODS: This was a cross sectional study that recruited a geographically representative sample of 749 adolescents living with HIV (ALHIV) and 825 HIV negative/untested adolescents aged 10-19 years in Nigeria. A face to face interviewer-administered questionnaire was used to collect information on their socio-demographic profile, awareness of contraceptive methods, and use of contraceptives. Study participants were recruited from six of the 36 states in Nigeria and the Federal Capital Territory. Chi-square was used to establish association between self-reported HIV status, age and sex, and awareness of contraceptive methods and condom use during last sex act. Significant predictors of 'good knowledge of modern contraceptive' and 'use of condoms by sexually active adolescents at last sex act' were also determined using logistic regression. RESULTS: Being a student significantly reduced the odds of having good knowledge about modern contraceptives (OR: 0.46; CI: 0.32-0.65; p<0.001). Having a tertiary level of education (OR: 1.36; CI: 1.12 1.64; p=0.002) and being HIV negative (OR: 2.92; CI: 1.98-4.32; p<0.001) increased the odds of having good knowledge of modern contraceptives. The only significant predictor for use of condoms at last sexual intercourse with a boy/girlfriend is self-efficacy about being about to negotiate condom use with a boy/girlfriend (OR: 141.01; CI: 14.99-1326.36; p<0.001). CONCLUSION: The study findings reiterate the need to introduce adolescents in general and ALHIV specifically to condom use in early adolescence prior to commencing sexual activities; and the need to provide adolescent friendly sexual and reproductive health services in Nigeria. PMID- 26556842 TI - Characteristics of the most viewed YouTubeTM videos related to bullying. AB - Bullying is an intentional act that can wreak havoc in the life of an individual. With more than 1 billion users, YouTubeTM is a powerful medium for disseminating information. The purpose of this study was to describe the extent to which content related to bullying is present on YouTubeTM with respect to source, content, number of views, length, and year uploaded. Collectively, the videos in this sample were viewed more than half a billion times. The source of the most widely viewed videos was consumers, and none of the most widely viewed videos was posted by a governmental agency or a professional organization. The most common content in the videos was describing or depicting violence (n=89). Over one-half addressed getting help (n=56). Suicide was mentioned in 38 of the videos. Additional investment by professional agencies is warranted to improve understanding about ways to increase the dissemination of positive messages about bullying prevention, and about helping adolescents who are bullied on social media. PMID- 26556843 TI - Burnout, depression and anxiety in preclinical medical students: a cross sectional survey. AB - OBJECTIVE: The purpose of this study was to assess the prevalences and correlates of adverse affective states (burnout-, depression- and anxiety-related symptoms) among preclinical medical students. METHODS: Self-report questionnaires were sent to all preclinical medical students of Leiden University Medical Center (n=1311). Burnout-related symptoms were measured using the Maslach Burnout Inventory General Survey (MBI-GS), depression and anxiety-related symptoms and vitality using the Symptom Questionnaire-48 (SQ-48). Furthermore, duration of sleep, quality of life (SF-36), need for recovery, happiness and dispositional optimism were assessed and analysed in relation to affective symptoms using regression analysis. RESULTS: Among the 433 responders (response rate=33.0%), prevalences of self-reported burnout-, depression- and anxiety-related symptoms were 46.0% (n=199), 27.0% (n=117) and 29.1% (n=126), respectively. Independent correlates for burnout-related symptoms were <6 h sleep per night (p=0.02), low happiness (p<0.001) and a high need for recovery (p<0.001). Independent correlates for both depression- and anxiety-related symptoms were low optimism (p<0.001; p<0.001, respectively), low happiness (p<0.001; p=0.001, respectively) and a high need for recovery (p=0.03; p<0.001, respectively). CONCLUSION: Prevalences for adverse affective states were high among preclinical medical students and mainly associated with personality trait-related factors and need for recovery, rather than work-related factors. These findings suggest that being a medical student increases one's risk to adverse affective states, and should inspire preventative initiatives. PMID- 26556844 TI - Is parenting a determinant of adolescent mental health? - A population based study in South India. AB - BACKGROUND: The transitional phase encompassing the physiological and psychological changes during our lifespan is termed as adolescence. Adolescents get mislead to substance use, violence related activities, dating relationships, unhealthy lifestyle. Minimal studies are conducted in India to identify the parenting factors that affect an adolescent's mind. The aim of our study was to explore the role of parenting and social surroundings on - adolescent's mental health and involvement in violence related activities. METHODS: Cross sectional study design was adopted. Semi structured questionnaire was used. Data obtained was entered and analyzed using SPSS 15. Proportions were used to report the findings. Chi-square test was used to find associations between mental health issues, involvement in violence related activities and Interpersonal Relationship (IPR) Status. Multiple logistic regressions were done to identify independent predictors of mental health. RESULTS: A total of 1770 adolescents participated. Proportion of adolescents with good IPR with parents reported to be having a better mental health status and low involvement in violent related activities. Schools also displayed similar effects. Neighborhood, peers did not display any significant effect on adolescent's mental health. Most significant predictor for adolescent mental health was IPR with parents and at school. CONCLUSION: The study highlights the need of a cordial environment at places which does influence the adolescent's mental health. Interventions enhancing the relationship status of adolescents with parents, at school must be carried out to observe the change in adolescent behavior. PMID- 26556845 TI - Cerivastatin represses atherogenic gene expression through the induction of KLF2 via isoprenoid metabolic pathways. AB - Earlier clinical studies have reported that cerivastatin has an anti atherosclerotic effect that is unique among the statins. In our study, human THP 1 macrophage cells were used to study the effects of various statins on the expressions of the atherosclerotic genes and Kruppel-like factor 2 (KLF2). Cerivastatin significantly inhibited the two atherosclerotic genes, monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor type 2 (CCR2) at both the mRNA and protein levels, while the other statins did not. Accordingly, cerivastatin was also the most potent inducer of KLF2 transcription in the macrophages. An siRNA-induced reduction in KLF2 expression blocked the inhibition of MCP-1 and CCR2 by cerivastatin. When the cells were further treated with mevalonate, farnesylpyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP), the effects of cerivastatin on KLF2, MCP-1 and CCR2 were obviously reversed. Thus, the results showed that cerivastatin was a potent inhibitor of the inflammation genes MCP-1 and CCR2 through the induction of KLF2. The regulation of MCP-1, CCR2 and KLF2 by cerivastatin was isoprenoid pathway dependent. Our studies suggest that the effect of cerivastatin on atherosclerotic genes and KLF2 expression may contribute to the cardioprotection observed in reported clinical studies. PMID- 26556846 TI - MGL induces nuclear translocation of EndoG and AIF in caspase-independent T cell death. AB - Macrophage galactose-type lectin (MGL) participates in the regulation of T cell apoptosis, but the exact death pathway remains unclear. Here, we demonstrated that MGL-induced T cell death occurs in a caspase-independent manner. Furthermore, MGL treatment triggers the translocation of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Because galectin-1 (Gal-1) can also initiate similar mitochondrial events, we speculate that this death pathway may be widely used by the lectin family. PMID- 26556847 TI - Differential effect of intranasally administrated kinin B1 and B2 receptor antagonists in Alzheimer's disease mice. AB - An Increasing body of evidence supports a critical role of brain inflammation in the pathogenesis of Alzheimer's disease. A principal aspect of the brain immune response to inflammation is the activation of microglia. It has been shown that the kinin system is activated during brain inflammation and previously we demonstrated that bradykinin B1 receptor agonist reduced microglial activation in vitro. The aim of the present study was to investigate the effects of bradykinin B1 or B2 receptor antagonists on microglial release of pro-inflammatory factors in BV2 microglia. In vivo, we focused on the effects of intranasally given kinin antagonists on amyloid burden and microglia/macrophage marker expression in brains of 5X familial Alzheimer's disease mice. The present data show that pharmacological antagonism of B1 receptor (R-715) but not B2 receptor (HOE-140) markedly increased nitric oxide and tumor necrosis factor alpha release from BV2 microglial cells. We also showed that intranasal treatment with R-715 but not HOE 140 of Alzheimer's mice enhanced amyloid beta burden and microglia/macrophages activation. Taken together, our data reveal a possible role for the bradykinin B1 receptor in neuroinflammation and in the control of Abeta accumulation in transgenic mice, possibly through regulation of glial cell responses. PMID- 26556849 TI - Art of airway management: the concept of 'Ma' (Japanese: , when 'less is more'). PMID- 26556850 TI - Difficult Airway Society 2015 guidelines for the management of unanticipated difficult intubation in adults: not just another algorithm. PMID- 26556851 TI - EpCAM based capture detects and recovers circulating tumor cells from all subtypes of breast cancer except claudin-low. AB - PURPOSE: The potential utility of circulating tumor cells (CTCs) as liquid biopsies is of great interest. We hypothesized that CTC capture using EpCAM based gating is feasible for most breast cancer subtypes. RESULTS: Cancer cells could be recovered from all intrinsic subtypes of breast cancer with IE/FACS, however, claudin-low cell lines showed very low capture rates compared to the four other groups (p = 0.03). IE/FACS detection of CTC mimic cells was time sensitive, emphasizing controlling for pre-analytic variables in CTC studies. Median fluorescent intensity for flow cytometry and RNA flow cell type characterization were highly correlated, predicting for CTC isolation across molecular subtypes. RNA-Seq of IE/FACS sorted single cell equivalents showed high correlation compared to bulk cell lines, and distinct gene expression signatures compared to PB. MATERIALS AND METHODS: Ten cell lines representing all major subtypes of breast cancer were spiked (as CTC mimics) into and recovered from peripheral blood (PB) using immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE/FACS). Flow cytometry and RNA flow were used to quantify the expression of multiple breast cancer related markers of interest. Two different RNA-Seq technologies were used to analyze global gene expression of recovered sorted cells compared to bulk cell lines and PB. CONCLUSIONS: EpCAM based IE/FACS detected and captured a portion of spiked cells from each of the 10 cell lines representing all breast cancer subtypes, including basal-like but not claudin-low cancers. The assay allows for the isolation of high quality RNA suitable for accurate RNA-Seq of heterogeneous rare cell populations. PMID- 26556848 TI - Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. AB - These guidelines provide a strategy to manage unanticipated difficulty with tracheal intubation. They are founded on published evidence. Where evidence is lacking, they have been directed by feedback from members of the Difficult Airway Society and based on expert opinion. These guidelines have been informed by advances in the understanding of crisis management; they emphasize the recognition and declaration of difficulty during airway management. A simplified, single algorithm now covers unanticipated difficulties in both routine intubation and rapid sequence induction. Planning for failed intubation should form part of the pre-induction briefing, particularly for urgent surgery. Emphasis is placed on assessment, preparation, positioning, preoxygenation, maintenance of oxygenation, and minimizing trauma from airway interventions. It is recommended that the number of airway interventions are limited, and blind techniques using a bougie or through supraglottic airway devices have been superseded by video- or fibre-optically guided intubation. If tracheal intubation fails, supraglottic airway devices are recommended to provide a route for oxygenation while reviewing how to proceed. Second-generation devices have advantages and are recommended. When both tracheal intubation and supraglottic airway device insertion have failed, waking the patient is the default option. If at this stage, face-mask oxygenation is impossible in the presence of muscle relaxation, cricothyroidotomy should follow immediately. Scalpel cricothyroidotomy is recommended as the preferred rescue technique and should be practised by all anaesthetists. The plans outlined are designed to be simple and easy to follow. They should be regularly rehearsed and made familiar to the whole theatre team. PMID- 26556852 TI - A network-based method to evaluate quality of reproducibility of differential expression in cancer genomics studies. AB - BACKGROUND: Personalized cancer treatments depend on the determination of a patient's genetic status according to known genetic profiles for which targeted treatments exist. Such genetic profiles must be scientifically validated before they is applied to general patient population. Reproducibility of findings that support such genetic profiles is a fundamental challenge in validation studies. The percentage of overlapping genes (POG) criterion and derivative methods produce unstable and misleading results. Furthermore, in a complex disease, comparisons between different tumor subtypes can produce high POG scores that do not capture the consistencies in the functions. RESULTS: We focused on the quality rather than the quantity of the overlapping genes. We defined the rank value of each gene according to importance or quality by PageRank on basis of a particular topological structure. Then, we used the p-value of the rank-sum of the overlapping genes (PRSOG) to evaluate the quality of reproducibility. Though the POG scores were low in different studies of the same disease, the PRSOG was statistically significant, which suggests that sets of differentially expressed genes might be highly reproducible. CONCLUSIONS: Evaluations of eight datasets from breast cancer, lung cancer and four other disorders indicate that quality based PRSOG method performs better than a quantity-based method. Our analysis of the components of the sets of overlapping genes supports the utility of the PRSOG method. PMID- 26556853 TI - TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas. AB - Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas. PMID- 26556854 TI - Clinical significance of accurate identification of lymph node status in distant metastatic gastric cancer. AB - PURPOSE: The clinical consequences of accurately identifying lymph node (LN) status in distant metastatic gastric cancer (DMGC) are unclear. We aimed to determine the prognostic significance of N stage, positive LN (PLN) count, and the positive LN ratio (LNR). We also retrospectively compared survival outcomes of DMGC patients stratified by LN dissection (LND). RESULTS: LND was performed in 1593 patients. The CSS was significantly different between groups divided according to N stage, PLN, and LNR in DMGC patients who underwent LND. Lower LNR was an independent predictor of longer survival in all kinds of patients cohorts, whereas PLN was not such a predictor. PLN count correlated with LND number and LNR. No correlation existed between LNR and LND number. Undergoing LND and having a higher number of dissected LNs were associated with superior CSS. MATERIALS AND METHODS: Data from 1889 DMGC patients treated between 2004 and 2009, and documented in the Surveillance, Epidemiology, and End Results (SEER) registry, were reviewed. Pearson's correlation coefficient and the Chi-square test were used to study the relationships between LND number, PLN count, N stage, and the LNR. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis, with the log-rank test performed for univariate analysis (UVA) and the Cox proportional hazards model employed for multivariate analysis (MVA). CONCLUSION: LN metastatic variables play important roles in the prognostic evaluation and treatment decisions of DMGC patients. Accurate identification of LN status in DMGC patients is critical. LND performance is associated with increased survival and has clinical practicability. PMID- 26556855 TI - The androgen receptor cytosine-adenine-guanine repeat length contributes to the development of epithelial ovarian cancer. AB - Ovarian cancer is the main cause of death among women with gynecological malignancies. Androgen and its receptors play an important role in ovarian cancer pathogenesis. Here, We aim to evaluate the relationship between AR CAG and GGN repeat length polymorphisms and Epithelial Ovarian Cancer (EOC) risk in a two stage, case-control study among Chinese women. The repeat length was analyzed as a categorical variable for CAG_A and GGN_A (average allele), CAG-S and GGN_S (shorter allele), CAG-L and GGN_L (longer allele), respectively. The median value of the repeat length among the controls was used as the cutoff point. Women with longer AR CAG repeats had a decreased risk of developing EOC. The results was replicated in an independent samples. Compared to those with shorter (<22) CAG_A repeat length, women with longer (>=22) CAG_A repeats length had a 31% decreased EOC risk (OR = 0.69, 95% CI: 0.62-0.77, P = 5.06 * 10-11). For CAG_S and CAG_L, the results remain consistent. However, we didn't detected any significant associations for GGN_A, GGN_S, and GGN_L. This should be the first study to examine the association between AR repeat length polymorphisms and ovarian cancer risk in a relatively large group of Asian women. PMID- 26556856 TI - Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. AB - Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patient-derived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSC-mediated disease progression. PMID- 26556857 TI - The bone marrow microenvironment enhances multiple myeloma progression by exosome mediated activation of myeloid-derived suppressor cells. AB - Exosomes, extracellular nanovesicles secreted by various cell types, modulate the bone marrow (BM) microenvironment by regulating angiogenesis, cytokine release, immune response, inflammation, and metastasis. Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells play crucial roles in MM development. We previously reported that BMSC-derived exosomes directly promote MM cell growth, whereas the other possible mechanisms for supporting MM progression by these exosomes are still not clear. Here, we investigated the effect of BMSC-derived exosomes on the MM BM cells with specific emphasis on myeloid-derived suppressor cells (MDSCs). BMSC-derived exosomes were able to be taken up by MM MDSCs and induced their expansion in vitro. Moreover, these exosomes directly induced the survival of MDSCs through activating STAT3 and STAT1 pathways and increasing the anti-apoptotic proteins Bcl-xL and Mcl-1. Inhibition of these pathways blocked the enhancement of MDSC survival. Furthermore, these exosomes increased the nitric oxide release from MM MDSCs and enhanced their suppressive activity on T cells. Taken together, our results demonstrate that BMSC-derived exosomes activate MDSCs in the BM through STAT3 and STAT1 pathways, leading to increased immunosuppression which favors MM progression. PMID- 26556858 TI - MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer. AB - DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for direct analysis of multiple proteins in tissue sections while maintaining the cellular and molecular integrity. We compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of IMS. DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and independent validation set were used to predict ploidy status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Five peaks (m/z 2,395 and 4,977 for diploid vs. aneuploid comparison as well as m/z 3,376, 6,663, and 8,581 for normal mucosa vs. carcinoma comparison) were significant in both SNN and ROC analysis. Among these, m/z 4,977 was identified as thymosin beta 4 (Tbeta-4). Tbeta-4 was subsequently validated in clinical samples using a tissue microarray to predict overall survival in colon cancer patients. PMID- 26556859 TI - Combined inhibition of heat shock proteins 90 and 70 leads to simultaneous degradation of the oncogenic signaling proteins involved in muscle invasive bladder cancer. AB - Heat shock protein 90 (HSP90) plays a critical role in the survival of cancer cells including muscle invasive bladder cancer (MIBC). The addiction of tumor cells to HSP90 has promoted the development of numerous HSP90 inhibitors and their use in clinical trials. This study evaluated the role of inhibiting HSP90 using STA9090 (STA) alone or in combination with the HSP70 inhibitor VER155008 (VER) in several human MIBC cell lines. While both STA and VER inhibited MIBC cell growth and migration and promoted apoptosis, combination therapy was more effective. Therefore, the signaling pathways involved in MIBC were systematically interrogated following STA and/or VER treatments. STA and not VER reduced the expression of proteins in the p53/Rb, PI3K and SWI/SWF pathways. Interestingly, STA was not as effective as VER or combination therapy in degrading proteins involved in the histone modification pathway such as KDM6A (demethylase) and EP300 (acetyltransferase) as predicted by The Cancer Genome Atlas (TCGA) data. This data suggests that dual HSP90 and HSP70 inhibition can simultaneously disrupt the key signaling pathways in MIBC. PMID- 26556860 TI - The Hsp90 inhibitor SNX-7081 is synergistic with fludarabine nucleoside via DNA damage and repair mechanisms in human, p53-negative chronic lymphocytic leukemia. AB - Clinical trials of heat shock protein 90 (Hsp90) inhibitors have been limited by high toxicity. We previously showed that the Hsp90 inhibitor, SNX-7081, synergizes with and restores sensitivity to fludarabine nucleoside (2-FaraA) in human chronic lymphocytic leukemia (CLL) cells with lesions in the p53 pathway (Best OG, et al., Leukemia Lymphoma 53:1367-75, 2012). Here, we used label-free quantitative shotgun proteomics and comprehensive bioinformatic analysis to determine the mechanism of this synergy. We propose that 2-FaraA-induced DNA damage is compounded by SNX-7081-mediated inhibition of DNA repair, resulting in enhanced induction of apoptosis. DNA damage responses are impaired in part due to reductions in checkpoint regulators BRCA1 and cyclin D1, and cell death is triggered following reductions of MYC and nucleolin and an accumulation of apoptosis-inducing NFkB2 p100 subunit. Loss of nucleolin can activate Fas mediated apoptosis, leading to the increase of pro-apoptotic proteins (BID, fas associated factor-2) and subsequent apoptosis of p53-negative, 2-FaraA refractory CLL cells. A significant induction of DNA damage, indicated by increases in DNA damage marker gammaH2AX, was observed following the dual drug treatment of additional cell lines, indicating that a similar mechanism may operate in other p53-mutated human B-lymphoid cancers. These results provide valuable insight into the synergistic mechanism between SNX-7081 and 2-FaraA that may provide an alternative treatment for CLL patients with p53 mutations, for whom therapeutic options are currently limited. Moreover, this drug combination reduces the effective dose of the Hsp90 inhibitor and may therefore alleviate any toxicity encountered. PMID- 26556861 TI - Therapeutics targeting CD90-integrin-AMPK-CD133 signal axis in liver cancer. AB - CD90 is used as a marker for cancer stem cell in liver cancer. We aimed to study the mechanism by which CD90 promoted liver cancer progression and identify the new therapeutic targets on CD90 signal pathway. Ectopic expression of CD90 in liver cancer cell lines enhanced anchorage-independent growth and tumor progression. Furthermore, CD90 promoted sphere formation in vitro and upregulated the expression of the cancer stem cell marker CD133. The CD133 expression was higher in CD45-CD90+ cells in liver cancer specimen. The natural carcinogenic molecules TGF-beta-1, HGF, and hepatitis B surface antigen increased the expression of CD90 and CD133. Inhibition of CD90 by either shRNA or antibody attenuated the induction of CD133 and anchorage-independent growth. Lentiviral delivery of CD133 shRNA abolished the tumorigenicity induced by CD90. Ectopic expression of CD90 induced mTOR phosphorylation and AMPK dephosphorylation. Mutation of integrin binding-RLD domain in CD90 attenuated the induction of CD133 and anchorage-independent growth. Similar results were observed after silencing beta3 integrin. Signaling analyses revealed that AMPK/mTOR and beta3 integrin were required for the induction of CD133 and tumor formation by CD90. Importantly, the energy restriction mimetic agent OSU-CG5 reduced the CD90 population in fresh liver tumor sample and repressed the tumor growth. In contrast, sorafenib did not decrease the CD90+ population. In conclusion, the signal axis of CD90-integrin-mTOR/AMPK-CD133 is critical for promoting liver carcinogenesis. Molecules inhibiting the signal axis, including OSU-CG5 and other inhibitors, may serve as potential novel cancer therapeutic targets in liver cancer. PMID- 26556862 TI - MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b. AB - Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR 221's targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression. PMID- 26556863 TI - Sorafenib, a multikinase inhibitor, induces formation of stress granules in hepatocarcinoma cells. AB - Stress granules (SGs) are cytoplasmic RNA multimeric bodies that form under stress conditions known to inhibit translation initiation. In most reported stress cases, the formation of SGs was associated with the cell recovery from stress and survival. In cells derived from cancer, SGs formation was shown to promote resistance to either proteasome inhibitors or 5-Fluorouracil used as chemotherapeutic agents. Despite these studies, the induction of SGs by chemotherapeutic drugs contributing to cancer cells resistance is still understudied. Here we identified sorafenib, a tyrosine kinase inhibitor used to treat hepatocarcinoma, as a potent chemotherapeutic inducer of SGs. The formation of SGs in sorafenib-treated hepatocarcionoma cells correlates with inhibition of translation initiation; both events requiring the phosphorylation of the translation initiation factor eIF2alpha. Further characterisation of the mechanism of sorafenib-induced SGs revealed PERK as the main eIF2alpha kinase responsible for SGs formation. Depletion experiments support the implication of PERK-eIF2alpha-SGs pathway in hepatocarcinoma cells resistance to sorafenib. This study also suggests the existence of an unexpected complex regulatory balance between SGs and phospho-eIF2alpha where SGs dampen the activation of the phospho eIF2alpha-downstream ATF4 cell death pathway. PMID- 26556865 TI - PPARalpha induces cell apoptosis by destructing Bcl2. AB - PPARalpha belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARalpha serves as an E3 ubiquitin ligase to govern Bcl2 protein stability. PPARalpha physically bound to Bcl2 protein. In this process, PPARalpha/C102 was critical for PPARalpha binding to BH3 domain of Bcl2, subsequently, PPARalpha transferred K48-linked polyubiquitin to lysine-22 site of Bcl2 resulting in its ubiquitination and proteasome-dependent degradation. Importantly, overexpression of PPARalpha enhanced cancer cell chemotherapy sensitivity. In contrast, silenced PPARalpha decreased this event. These findings revealed a novel mechanism of PPARalpha governed endogenous Bcl2 protein stability leading to reduced cancer cell chemoresistance, which provides a potential drug target for cancer treatment. PMID- 26556864 TI - Chemopreventive effect of resveratrol and apocynin on pancreatic carcinogenesis via modulation of nuclear phosphorylated GSK3beta and ERK1/2. AB - Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki 67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3beta and ERK1/2 signaling. Further, decreased levels of GSK3beta(Ser9) and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3beta(Ser9) was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3beta(Ser9) and ERK1/2 in the nucleus, resulting in inhibition of the AKT GSK3beta and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer. PMID- 26556866 TI - The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients. AB - The CRNDE gene seems to play an oncogenic role in cancers, though its exact function remains unknown. Here, we tried to assess its usefulness as a molecular prognostic marker in ovarian cancer. Based on results of our microarray studies, CRNDE transcripts were further analyzed by Real-Time qPCR-based profiling of their expression. The qPCR study was conducted with the use of personally designed TaqMan assays on 135 frozen tissue sections of ovarian carcinomas from patients treated with platinum compounds and either cyclophosphamide (PC, N = 32) or taxanes (TP, N = 103). Elevated levels of two different CRNDE transcripts were a negative prognostic factor; they increased the risk of death and recurrence in the group of patients treated with TP, but not PC (DNA-damaging agents only). Higher associations were found for overexpression of the short CRNDE splice variant (FJ466686): HR 6.072, 95% CI 1.814-20.32, p = 0.003 (the risk of death); HR 15.53, 95% CI 3.812-63.28, p < 0.001 (the risk of recurrence). Additionally, accumulation of the TP53 protein correlated with decreased expression of both CRNDE transcripts in tumor cells. Our results depict CRNDE as a potential marker of poor prognosis in women with ovarian carcinomas, and suggest that its significance depends on the therapeutic regimen used. PMID- 26556867 TI - Growth-stimulatory activity of TIMP-2 is mediated through c-Src activation followed by activation of FAK, PI3-kinase/AKT, and ERK1/2 independent of MMP inhibition in lung adenocarcinoma cells. AB - Tissue inhibitors of metalloproteinases (TIMPs) control extracellular matrix (ECM) homeostasis by inhibiting the activity of matrix metalloproteinases (MMPs), which are associated with ECM turnover. Recent studies have revealed that TIMPs are implicated in tumorigenesis in both MMP-dependent and MMP-independent manners. We examined a mechanism by which TIMP-2 stimulated lung adenocarcinoma cell proliferation, independent of MMP inhibition. The stimulation of growth by TIMP-2 in A549 cells required c-Src kinase activation. c-Src kinase activity, induced by TIMP-2, concomitantly increased FAK, phosphoinositide 3-kinase (PI3 kinase)/AKT, and ERK1/2 activation. Selective knockdown of integrin alpha3beta1, known as a TIMP-2 receptor, did not significantly change TIMP-2 growth promoting activity. Furthermore, we showed that high TIMP-2 expression in lung adenocarcinomas is associated with a worse prognosis from multiple cohorts, especially for stage I lung adenocarcinoma. Through integrated analysis of The Cancer Genome Atlas data, TIMP-2 expression was significantly associated with the alteration of driving genes, c-Src activation, and PI3-kinase/AKT pathway activation. Taken together, our results demonstrate that TIMP-2 stimulates lung adenocarcinoma cell proliferation through c-Src, FAK, PI3-kinase/AKT, and ERK1/2 pathway activation in an MMP-independent manner. PMID- 26556868 TI - Recruited mast cells in the tumor microenvironment enhance bladder cancer metastasis via modulation of ERbeta/CCL2/CCR2 EMT/MMP9 signals. AB - Early clinical studies suggested that infiltrating mast cells could be associated with a poor outcome in bladder cancer (BCa) patients. The mechanisms of how mast cells influence the BCa progression, however, are unclear. Using the human clinical BCa sample survey and in vitro co-culture systems, we found BCa cells could recruit more mast cells than the surrounding non-malignant urothelial cells. The consequences of this better recruitment of mast cells toward BCa cells could then enhance BCa cell invasion. Mechanism dissection revealed that the enhanced BCa cell invasion could function via up-regulation of the estrogen receptor beta (ERbeta) in both mast cells and BCa cells, which resulted in the increased CCL2/CCR2/EMT/MMP9 signals. Using the pre-clinical mouse BCa model, we further validated the mast cell-promoted BCa invasion. Interruption of the newly identified ERbeta/CCL2/CCR2/EMT/MMP9 pathway via either ERbeta-siRNA, ERbeta antagonist PHTPP, or CCR2 antagonist can effectively reverse the mast cell enhanced BCa cells invasion. Together, our finding could lead to the development of an alternative new therapeutic approach to better treat BCa metastasis. PMID- 26556869 TI - Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality. AB - Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality. PMID- 26556871 TI - In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays. AB - Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment. PMID- 26556872 TI - Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner. AB - Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan(r) miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-alpha, IL-1beta, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1alpha were increased, and IFN-gamma expression was decreased after radiation, whereas, IL-6, IFN-gamma, TNF-alpha, IL 1beta, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1alpha were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment. PMID- 26556873 TI - Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis. AB - P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP 1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis. PMID- 26556874 TI - Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche. AB - Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/beta catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC. PMID- 26556875 TI - STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell. AB - Signaling transducer and activator 3 (STAT3) and cancer stem cells (CSCs) have garnered huge attention as a therapeutic focus, based on evidence that they may represent an etiologic root of tumor initiation and radio-chemoresistance. Here, we investigated the high phosphorylation status of STAT3 (p-STAT3) and its correlation with self-renewal markers in head neck squamous cell carcinoma (HNSCC). Over-expression of p-STAT3 was found to have increased in post chemotherapy HNSCC tissue. We showed that blockade of p-STAT3 eliminated both bulk tumor and side population (SP) cells with characteristics of CSCs in vitro. Inhibition of p-STAT3 using small molecule S3I-201 significantly delayed tumorigenesis of spontaneous HNSCC in mice. Combining blockade of p-STAT3 with cytotoxic drugs cisplatin, docetaxel, 5-fluorouracil (TPF) enhanced the antitumor effect in vitro and in vivo with decreased tumor sphere formation and SP cells. Taken together, our results advocate blockade of p-STAT3 in combination with conventional chemotherapeutic drugs enhance efficacy by improving CSCs eradication in HNSCC. PMID- 26556876 TI - Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. AB - Multidrug resistance (MDR) is the leading cause of treatment failure in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2, play a key role in mediating MDR by pumping anticancer drugs out from cancer cells. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) currently in phase III clinical trial for the treatment of non-small cell lung cancer. Here, we found that ceritinib remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo. Ceritinib significantly increased the intracellular accumulation of chemotherapeutic agents such as doxorubicin (DOX) by inhibiting ABCB1 or ABCG2-mediated drug efflux in the transporters-overexpressing cells. Mechanistically, ceritinib is likely a competitive inhibitor of ABCB1 and ABCG2 because it competed with [(125)I] iodoarylazidoprazosin for photo affinity labeling of the transporters. On the other hand, at the transporters-inhibiting concentrations, ceritinib did not alter the expression level of ABCB1 and ABCG2, and phosphorylation status of AKT and ERK1/2. Thus the findings advocate further clinical investigation of combination chemotherapy of ceritinib and other conventional chemotherapeutic drugs in chemo-refractory cancer patients. PMID- 26556879 TI - Erratum for Kulohoma et al., Comparative genomic analysis of meningitis- and bacteremia-causing pneumococci identifies a common core genome. PMID- 26556877 TI - gammaKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers. AB - Over the last decade, breast cancer mortality has declined. However, triple negative breast cancer (TNBC) remains a challenging problem mostly due to early recurrence and lack of molecularly driven treatments. There is a critical need to identify subgroups of TNBC with common molecular features that can be therapeutically targeted. Here we show that in contrast to Klotho and betaKlotho, the third member of the Klotho protein family, gammaKlotho, is overexpressed in more than 60% of TNBCs and correlates with poorer disease progression. Furthermore, we find that gammaKlotho is expressed in a subset of TNBC cell lines promoting cell growth. Importantly, we demonstrate that in these cells gammaKlotho is necessary for cell survival and that its depletion leads to constitutive ERK activation, cell cycle arrest and apoptosis. Interestingly, we observe increased oxidative stress in gammaKlotho-depleted cells suggesting that gammaKlotho enables cancer cells to cope with an oxidative environment and that cells become dependent on its expression to maintain this survival advantage. These findings indicate that gammaKlotho might be a potential marker for patients that would benefit from treatments that alter oxidative stress and constitutes a novel drug target for a subset of TN breast cancers. PMID- 26556880 TI - Correction for Santander et al., Fur-regulated iron uptake system of Edwardsiella ictaluri and its influence on pathogenesis and immunogenicity in the catfish host. PMID- 26556881 TI - Correction for Zhang et al., Toxin-mediated paracellular transport of antitoxin antibodies facilitates protection against Clostridium difficile infection. PMID- 26556883 TI - Stochastic games. AB - In 1953, Lloyd Shapley contributed his paper "Stochastic games" to PNAS. In this paper, he defined the model of stochastic games, which were the first general dynamic model of a game to be defined, and proved that it admits a stationary equilibrium. In this Perspective, we summarize the historical context and the impact of Shapley's contribution. PMID- 26556884 TI - Science and Culture: Of waves and wallpaper. PMID- 26556885 TI - Structural and functional dynamics of photosynthetic antenna complexes. PMID- 26556887 TI - Losing ground at midlife in America. PMID- 26556888 TI - Reply to Fiscella: The phases of biomedical research should be studied to optimize health outcomes. PMID- 26556889 TI - Distinguishing phases of biomedical research is critical to improving health outcomes. PMID- 26556890 TI - PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle. AB - Skeletal muscle atrophy remains a complication occurring both as a natural response to muscle disuse and as a pathophysiological response to illness such as diabetes mellitus and nerve injury, such as traumatic muscle denervation. The ubiquitin-proteasome system (UPS) is the predominant proteolytic machinery responsible for atrophy of skeletal muscle, and Nedd4-1 (neural precursor cell expressed developmentally down-regulated 4-1) is one of a series of E3 ubiquitin ligases identified to mediate inactivity-induced muscle wasting. Targets of Nedd4 1 mediated ubiquitination in skeletal muscle remain poorly understood. In the present study, we identified PDLIM7 (PDZ and LIM domain 7, Enigma), a member of the PDZ-LIM family of proteins, as a novel target of Nedd4-1 in skeletal muscle. The PDZ-LIM family of proteins is known to regulate muscle development and function. We show that Nedd4-1 expression in muscle atrophied by denervation is co-incident with a decrease in PDLIM7 and that PDLIM7 protein levels are stabilized in denervated muscle of Nedd4-1 skeletal muscle-specific knockout mice (SMS-KO). Exogenous PDLIM7 and Nedd4-1 transfected into human embryonic kidney (HEK)293 cells co-immunoprecipitate through binding between the PY motif of PDLIM7 and the second and third WW domains of Nedd4-1 and endogenous PDLIM7 and Nedd4-1 interact in the cytoplasm of differentiated C2C12 myotubes, leading to PDLIM7 ubiquitination. These results identify PDLIM7 as a bona fide skeletal muscle substrate of Nedd4-1 and suggest that this interaction may underlie the progression of skeletal muscle atrophy. This offers a novel therapeutic target that could be potentially used to attenuate muscle atrophy. PMID- 26556891 TI - Plasma-derived and synthetic high-density lipoprotein inhibit tissue factor in endothelial cells and monocytes. AB - HDL (high-density lipoproteins) exert anti-thrombotic activities by preventing platelet adhesion and activation and by stimulating the protein C pathway and fibrinolysis. The aim of the present study was to assess the effect of plasma derived and synthetic HDL on endothelial and monocyte expression of TF (tissue factor), the primary initiator of coagulation. HDL inhibited TF expression and activity in stimulated endothelial cells and monocytes in a dose-dependent way. Synthetic HDL fully retain the ability to inhibit TF expression in a dose dependent manner; lipid-free apoA-I (apolipoprotein A-I) was not effective and neither was sphingosine 1-phosphate involved. HDL-mediated TF inhibition was due to a modulation of cellular cholesterol content through the interaction with SR BI (scavenger receptor BI); downstream, HDL inhibited the activation of p38 MAPK (mitogen-activated protein kinase) and the repression of the PI3K (phosphoinositide 3-kinase) pathway responsible for TF expression. In vivo, human apoA-I-transgenic mice displayed a reduced aortic TF expression compared with wild-type animals and TF plasma levels were increased in subjects with low HDL-C (HDL-cholesterol) levels compared with high HDL-C subjects. Thus the anti thrombotic activity of HDL could also be mediated by the inhibition of TF expression and activity in endothelial cells and monocytes; synthetic HDL retain the inhibitory activity of plasma-derived HDL, supporting the hypothesis that synthetic HDL infusion may be beneficial in the setting of acute coronary syndrome. PMID- 26556892 TI - Prenatal and lactation nicotine exposure affects Sertoli cell and gonadotropin levels in rats. AB - Nicotine is largely consumed in the world as a component of cigarettes. It can cross the placenta and reach the milk of smoking mothers. This drug induces apoptosis, affects sex hormone secretion, and leads to male infertility. To investigate the exposure to nicotine during the whole intrauterine and lactation phases in Sertoli cells, pregnant rats received nicotine (2 mg/kg per day) through osmotic minipumps. Male offsprings (30, 60, and 90 days old) had blood collected for hormonal analysis (FSH and LH) and their testes submitted for histophatological study, analysis of the frequency of the stages of seminiferous epithelium cycle, immunolabeling of apoptotic epithelial cells (TUNEL and Fas/FasL), analysis of the function and structure of Sertoli cells (respectively using transferrin and vimentin immunolabeling), and analysis of Sertoli-germ cell junctional molecule (beta-catenin immunolabeling). The exposure to nicotine increased the FSH and LH plasmatic levels in adult rats. Although nicotine had not changed the number of apoptotic cells, neither in Fas nor FasL expression, it provoked an intense sloughing of epithelial cells and also altered the frequency of some stages of the seminiferous epithelium cycle. Transferrin and beta-catenin expressions were not changed, but vimentin was significantly reduced in the early stages of the seminiferous cycle of the nicotine-exposed adult rats. Thus, we concluded that nicotine exposure during all gestational and lactation periods affects the structure of Sertoli cells by events causing intense germ cell sloughing observed in the tubular lumen and can compromise the fertility of the offspring. PMID- 26556893 TI - Blood-testis barrier and Sertoli cell function: lessons from SCCx43KO mice. AB - The gap junction protein connexin43 (CX43) plays a vital role in mammalian spermatogenesis by allowing for direct cytoplasmic communication between neighbouring testicular cells. In addition, different publications suggest that CX43 in Sertoli cells (SC) might be important for blood-testis barrier (BTB) formation and BTB homeostasis. Thus, through the use of the Cre-LoxP recombination system, a transgenic mouse line was developed in which only SC are deficient of the gap junction protein, alpha 1 (Gja1) gene. Gja1 codes for the protein CX43. This transgenic mouse line has been commonly defined as the SC specific CX43 knockout (SCCx43KO) mouse line. Within the seminiferous tubule, SC aid in spermatogenesis by nurturing germ cells and help them to proliferate and mature. Owing to the absence of CX43 within the SC, homozygous KO mice are infertile, have reduced testis size, and mainly exhibit spermatogenesis arrest at the level of spermatogonia, seminiferous tubules containing only SC (SC-only syndrome) and intratubular SC-clusters. Although the SC specific KO of CX43 does not seem to have an adverse effect on BTB integrity, CX43 influences BTB composition as the expression pattern of different BTB proteins (like OCCLUDIN, beta-CATENIN, N-CADHERIN, and CLAUDIN11) is altered in mutant males. The supposed roles of CX43 in dynamic BTB regulation, BTB assembly and/or disassembly and its possible interaction with other junctional proteins composing this unique barrier are discussed. Data collectively indicate that CX43 might represent an important regulator of dynamic BTB formation, composition and function. PMID- 26556894 TI - Effects of Inspiratory Muscle Training and Calisthenics-and-Breathing Exercises in COPD With and Without Respiratory Muscle Weakness. AB - BACKGROUND: Patients with COPD may experience respiratory muscle weakness. Two therapeutic approaches to the respiratory muscles are inspiratory muscle training and calisthenics-and-breathing exercises. The aims of the study are to compare the effects of inspiratory muscle training and calisthenics-and-breathing exercises associated with physical training in subjects with COPD as an additional benefit of strength and endurance of the inspiratory muscles, thoracoabdominal mobility, physical exercise capacity, and reduction in dyspnea on exertion. In addition, these gains were compared between subjects with and without respiratory muscle weakness. METHODS: 25 subjects completed the study: 13 composed the inspiratory muscle training group, and 12 composed the calisthenics and-breathing exercises group. Subjects were assessed before and after training by spirometry, measurements of respiratory muscle strength and test of inspiratory muscle endurance, thoracoabdominal excursion measurements, and the 6 min walk test. Moreover, scores for the Modified Medical Research Council dyspnea scale were reported. RESULTS: After intervention, there was a significant improvement in both groups of respiratory muscle strength and endurance, thoracoabdominal mobility, and walking distance in the 6-min walk test. Additionally, there was a decrease of dyspnea in the 6-min walk test peak. A difference was found between groups, with higher values of respiratory muscle strength and thoracoabdominal mobility and lower values of dyspnea in the 6-min walk test peak and the Modified Medical Research Council dyspnea scale in the inspiratory muscle training group. In the inspiratory muscle training group, subjects with respiratory muscle weakness had greater gains in inspiratory muscle strength and endurance. CONCLUSIONS: Both interventions increased exercise capacity and decreased dyspnea during physical effort. However, inspiratory muscle training was more effective in increasing inspiratory muscle strength and endurance, which could result in a decreased sensation of dyspnea. In addition, subjects with respiratory muscle weakness that performed inspiratory muscle training had higher gains in inspiratory muscle strength and endurance but not of dyspnea and submaximal exercise capacity. (ClinicalTrials.gov registration NCT01510041.). PMID- 26556895 TI - Complications of Convex-Probe Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Multi-Center Retrospective Study. AB - BACKGROUND: Infrequent serious complications of convex-probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been reported. The aim of this study was to assess serious complications related to convex-probe EBUS-TBNA and to determine the complication rate in a large group of subjects. METHODS: In this retrospective study, a 15-item questionnaire on features of cases with EBUS-TBNA complications was sent to experienced bronchoscopists performing convex-probe EBUS-TBNA at 3 pulmonary centers. The medical records were then reviewed by these bronchoscopists to complete the questionnaire. Hemorrhage responsive to topical treatment, temporary laryngospasm/bronchospasm, transient oxygen desaturation, and fever lasting <24 h were excluded. Only complications requiring further treatment/intervention were considered serious. The rate of serious complications was calculated from the obtained data. RESULTS: In a total of 3,123 cases within a 5-y period, EBUS-TBNA was performed for staging lung cancer in 15.8%, diagnosis in 67.5%, and diagnosis and staging in 16.3%. Of the 3,123, 11.6% had parenchymal lesions adjacent to major airways. EBUS-TBNA was performed 11,753 times (3.76/case) at 6,115 lymph node stations and lesions (1.92/station or lesion). Five serious complications were recorded (0.16%): fever lasting >24 h, infection of bronchogenic cyst, mediastinal abscess, pericarditis, and pneumomediastinitis with empyema, each in one case. Four complications occurred in cases diagnosed with benign disease by EBUS-TBNA. All complications were treated with broad-spectrum antibiotics. Four subjects were hospitalized for 21.7 +/- 20.7 d. CONCLUSIONS: Convex-probe EBUS TBNA is a safe method in general. However, serious complications, including infections, can be encountered rarely. All precautions should be taken for complications before and during the procedure. PMID- 26556896 TI - Evaluation of the Infection-Related Ventilator-Associated Events Algorithm for Ventilator-Associated Pneumonia Surveillance in a Trauma Population. AB - BACKGROUND: The Centers for Disease Control and Prevention have recently introduced new ventilator-associated pneumonia (VAP) surveillance on the basis of the infection-related ventilator-associated complication (IVAC) definition. We aim to evaluate the accuracy of this new IVAC algorithm for detecting VAP according to the 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) definition as the reference diagnosis (VAP-NHSN) in high-risk trauma patients. METHODS: This retrospective single-center study included all trauma subjects who were admitted to the ICU, required mechanical ventilation for >48 h, and received a blood transfusion. The new IVAC surveillance and the criteria for VAP-NHSN diagnosis were applied. The accuracy of the new IVAC surveillance for detecting VAP-NHSN was determined, and the clinical outcomes were compared between groups. RESULTS: The sensitivity, specificity, and positive and negative predictive values of IVAC for VAP-NSHN identification were 28.12%, 91.45, 58.06%, and 75.14%, respectively. Subjects with IVAC, VAP-NHSN, or both had higher morbidity when compared with those without IVAC and VAP-NHSN. Subjects with IVAC only had lower morbidity compared with those with VAP-NHSN only or those with both IVAC and VAP-NHSN. There was no significant difference in clinical outcomes between subjects with VAP-NHSN only and those with both IVAC and VAP-NHSN. CONCLUSIONS: IVAC criteria had a low accuracy for identifying VAP-NHSN in subjects with high-risk trauma. PMID- 26556898 TI - Patient-Ventilator Interaction During Noninvasive Ventilation in Simulated COPD. AB - BACKGROUND: During noninvasive ventilation (NIV) of COPD patients, delayed off cycling of pressure support can cause patient ventilator mismatch and NIV failure. This systematic experimental study analyzes the effects of varying cycling criteria on patient-ventilator interaction. METHODS: A lung simulator with COPD settings was connected to an ICU ventilator via helmet or face mask. Cycling was varied between 10 and 70% of peak inspiratory flow at different breathing frequencies (15 and 30 breaths/min) and pressure support levels (5 and 15 cm H2O) using the ventilator's invasive and NIV mode with and without an applied leakage. RESULTS: Low cycling criteria led to severe expiratory cycle latency. Augmenting off-cycling reduced expiratory cycle latency (P < .001), decreased intrinsic PEEP, and avoided non-supported breaths. Setting cycling to 50% of peak inspiratory flow achieved best synchronization. Overall, using the helmet interface increased expiratory cycle latency in almost all settings (P < .001). Augmenting cycling from 10 to 40% progressively decreased expiratory pressure load (P < .001). NIV mode decreased expiratory cycle latency compared with the invasive mode (P < .001). CONCLUSION: Augmenting the cycling criterion above the default setting (20-30% peak inspiratory flow) improved patient ventilator synchrony in a simulated COPD model. This suggests that an individual approach to cycling should be considered, since interface, level of pressure support, breathing frequency, and leakage influence patient-ventilator interaction and thus need to be considered. PMID- 26556897 TI - The Relationship Among Oxidative and Anti-Oxidative Parameters and Myeloperoxidase in Subjects With Obstructive Sleep Apnea Syndrome. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in sleep. It is characterized by intermittent hypoxia leading to hypoxemia, hypercapnia, sleep fragmentation, and increased respiratory efforts. We evaluated the relationship between OSA and myeloperoxidase activity, the oxidative stress index (OSI), total anti-oxidative capacity (TAC), and total oxidative capacity (TOC). METHODS: A total of 70 consecutive subjects (mean age +/- SD: 51.7 +/- 11.7 y) were diagnosed with OSA after a night polysomnography recording between January 2014 and June 2014 consecutively. The subjects in the OSA group were divided according to the severity of the disease into three subgroups, consisting of 11 mild, 17 moderate OSA, and 22 severe OSA subjects. Twenty subjects with simple snoring were considered as the control group. RESULTS: We included a total of 70 subjects: 50 with OSA (11 subjects 6.9% mild, 17 subjects 24.7% moderate, and 22 subjects 68.5% severe) and 20 subjects with simple snoring as control cases. The mean age of the mild OSA subjects was 44.5 +/- 11.7 y, moderate OSA subjects' mean age was 52.5 +/- 11.9 y, and severe OSA subjects' mean age was 52.1 +/- 10.1 y; 54.2% were male. There were statistically significant differences among the 4 groups' OSI, TAC, and TOC levels, but there was no statistically significant difference between the other values. The mean myeloperoxidase, TOC, OSI, and TAC levels were 55 +/- 12, 61.2 +/- 21.1, 3.04 +/- 1.04, and 2.03 +/- 0.4 in the mild OSA group; 58.7 +/- 17.2, 60 +/- 18.9, 3.05 +/ 1, and 2 +/- 0.33 in the moderate OSA group; 56.6 +/- 17.9, 52.1 +/- 17.9, 2.7 +/- 0.76, and 1.94 +/- 0.24 in the severe OSA group; and 49.8 +/- 12.5, 54.3 +/- 16.4, 3.08 +/- 0.88, and 1.78 +/- 0.26 in the control group, respectively. CONCLUSIONS: In our study, there were no differences in studied parameters between control and OSA groups. Furthermore, our low number of cases was a restrictive factor. Further studies should be undertaken to clarify this relation. PMID- 26556899 TI - Prospective Observational Study of Predictors of Re-Intubation Following Extubation in the Surgical ICU. AB - BACKGROUND: Re-intubation is associated with high morbidity and mortality. There is limited information regarding the risk factors that predispose patients admitted to the surgical ICU to re-intubation. We hypothesized that preoperative comorbidities, acquired muscular weakness, and renal dysfunction would be predictors of re-intubation in the surgical ICU population. METHODS: This was a prospective observational study in 2 surgical ICUs of a large tertiary hospital. All patients who were extubated during their surgical ICU stay were included. Demographic and clinical data were collected before and after extubation. The primary outcome was re-intubation within 72 h. Using multivariate logistic regression analysis, independent risk factors of re-intubation were determined, and a prediction score was developed. RESULTS: Between December 1, 2012, and January 31, 2014, we included 764 consecutive subjects. Of these, 65 subjects (8.5%) required re-intubation. Independent risk factors of re-intubation were blood urea nitrogen level of >8.2 mmol/L (odds ratio [OR] 3.66, 95% CI 1.97 6.80), hemoglobin level of <75 g/L (OR 2.10, 95% CI 1.23-3.61), and muscle strength of <=3 (OR 2.03, 95% CI 1.16-3.55). The presence of all 3 risk factors was associated with an estimated probability for re-intubation of 26.8%. CONCLUSIONS: In noncardiac surgery, surgical ICU subjects, elevated blood urea nitrogen level, low hemoglobin level, and muscle weakness were identified as independent risk factors for re-intubation. The presence of these risk factors can potentially aid clinicians in making informed decisions regarding optimal airway management in patients considered for an extubation attempt. (ClinicalTrials.gov registration NCT01967056.). PMID- 26556900 TI - Neonatal Pneumothorax Pressures Surpass Higher Threshold in Lung Recruitment Maneuvers: An In Vivo Interventional Study. AB - BACKGROUND: Causing pneumothorax is one of the main concerns of lung recruitment maneuvers in pediatric patients, especially newborns. Therefore, these maneuvers are not performed routinely during anesthesia. Our objective was to determine the pressures that cause pneumothorax in healthy newborns by a prospective experimental study of 10 newborn piglets (<48 h old) with healthy lungs under general anesthesia. METHODS: The primary outcome was peak inspiratory pressure (PIP) causing pneumothorax. Animals under anesthesia and bilateral chest tube catheterization were randomly allocated to 2 groups: one with PEEP and fixed inspiratory driving pressure of 15 cm H2O (PEEP group) and the second one with PEEP = 0 cm H2O and non-fixed inspiratory driving pressure (zero PEEP group). In both groups, the ventilation mode was pressure-controlled, and PIP was raised at 2-min intervals, with steps of 5 cm H2O until air leak was observed through the chest tubes. The PEEP group raised PIP through 5-cm H2O PEEP increments, and the zero PEEP group raised PIP through 5-cm H2O inspiratory driving pressure increments. RESULTS: Pneumothorax was observed with a PIP of 90.5 +/- 15.7 cm H2O with no statistically significant differences between the PEEP group (92 +/- 14.8 cm H2O) and the zero PEEP group (89 +/- 18.2 cm H2O). The zero PEEP group had hypotension, with a PIP of 35 cm H2O; the PEEP group had hypotension, with a PIP of 60 cm H2O (P = .01). The zero PEEP group presented bradycardia, with PIP of 40 cm H2O; the PEEP group presented bradycardia, with PIP of 70 cm H2O (P = .002). CONCLUSIONS: Performing recruitment maneuvers in newborns without lung disease is a safe procedure in terms of pneumothorax. Pneumothorax does not seem to occur in the clinically relevant PIPs of <50 cm H2O. Hemodynamic impairment may occur with high driving pressures. More studies are needed to determine the exact hemodynamic impact of these procedures and pneumothorax PIP in poorly compliant lungs. PMID- 26556901 TI - Asthma Control Assessment Tools. AB - Both the National Asthma Education and Prevention Program Expert Panel Report 3 and the 2015 Global Initiative for Asthma guidelines identify achieving and maintaining asthma control as goals of therapy, and they emphasize periodic assessment of asthma control once treatment is established. Accurate assessment of asthma control is difficult due to the complexity of asthma control and due to the limitations in the traditional methods of assessment, such as lung function tests, physician assessment, and patients' self-assessment. Relying solely on the role of lung function tests is insufficient to reflect the status of asthma control, since patients with asthma may have normal spirometry between exacerbations. Clinicians often overestimate the level of asthma control. Similarly, it is not uncommon for patients to overestimate how well their asthma is controlled, and, therefore, they under-report asthma symptoms and fail to recognize the impact that asthma has on their daily life. As a result, several tools have been developed to quantify the level of asthma control, identify patients at risk, and evaluate the effect of asthma management. This review examines the commonly used asthma control assessment tools in terms of content, psychometric properties, methods of administration, limitations, and ability to reflect the overall status of asthma control, which can aid clinicians in selecting the most appropriate tool for their needs. PMID- 26556902 TI - Aerobic scope explains individual variation in feeding capacity. AB - Links between metabolism and components of fitness such as growth, reproduction and survival can depend on food availability. A high standard metabolic rate (SMR; baseline energy expenditure) or aerobic scope (AS; the difference between an individual's maximum and SMR) is often beneficial when food is abundant or easily accessible but can be less important or even disadvantageous when food levels decline. While the mechanisms underlying these context-dependent associations are not well understood, they suggest that individuals with a higher SMR or AS are better able to take advantage of high food abundance. Here we show that juvenile brown trout (Salmo trutta) with a higher AS were able to consume more food per day relative to individuals with a lower AS. These results help explain why a high aerobic capacity can improve performance measures such as growth rate at high but not low levels of food availability. PMID- 26556903 TI - Evaluating differential effects using regression interactions and regression mixture models. AB - Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design. PMID- 26556904 TI - Precancerous Lesions of the Cervix, Vulva and Vagina According to the 2014 WHO Classification of Tumors of the Female Genital Tract. PMID- 26556905 TI - Statement by the Kommission Ovar of the AGO: The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer. AB - More than 25 years after the last revision, in 2012 the FIGO Oncology Committee began revising the FIGO classification for staging ovarian, Fallopian tube and primary peritoneal cancers. The new classification has become effective with its publication at the beginning of 2014. Following recent findings on the pathogenesis of ovarian, Fallopian tube and primary peritoneal cancer and reflecting standard clinical practice, the three entities have now been classified uniformly. The histological subtype is included (high-grade serous - HGSC; low-grade serous - LGSC; mucinous - MC; clear cell - CCC; endometrioid - EC). Stages III and IV have been fundamentally changed: stage IIIA now refers to a localized tumor limited to the pelvis with (only) retroperitoneal lymph node metastasis (formerly classified as IIIC). Stage IV has been divided into IVA and IVB, with IVA defined as malignant pleural effusion and IVB as parenchymatous or extra-abdominal metastasis including inguinal and mediastinal lymph node metastasis as well as umbilical metastasis. A new WHO classification was published almost concurrently. The classification of serous tumors addresses the issue of the tubal carcinogenesis of serous ovarian cancer, even if no tubal precursor lesions are found for up to 30 % of serous high-grade cancers. The number of subgroups was reduced and subgroups now include only high-grade serous, low-grade serous, mucinous, seromucinous, endometrioid, clear cell and Brenner tumors. The category "transitional cell carcinomas" has been dropped and the classification "seromucinous tumors" has been newly added. More attention has been focused on the role of borderline tumors as a stage in the progression from benign to invasive lesions. PMID- 26556906 TI - Gestational Trophoblastic Disorders: An Update in 2015. AB - Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumours. They encompass premalignant disorders including complete (CHM), partial hydatidiform mole (PHM), exaggerated placental site (EPS), and placental-site nodule (PSN) as well as malignant disorders (also known as "gestational trophoblastic neoplasia [GTN]") including invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumour (PSTT), and epitheloid trophoblastic tumours (ETT) (Fig. 1). Originally, GTD develop from abnormal proliferation of trophoblastic tissue and form botryoid arranged vesicles. Premalignant moles are usually treated by suction curettage while persistent and recurrent moles and malignant forms require systemic therapy with methotrexate or combination chemotherapy consisting of etoposide, actimomycin D, methotrexate, vincristine, and cyclophosphamide (EMA-CO). beta-human chorion gonadotropin (beta hCG) plays a crucial role in diagnosis and monitoring therapeutic effects. Since the definitive diagnosis cannot be obtained by histology in most cases, persistent or recurrent disease is diagnosed by elevated or persistent serum levels of beta-hCG. While curing rates are described to be as high as 98 %, GTD may initially present, recur, or end up as a metastasising systemic disease. This underlines the importance of a regular and consistent follow-up after treatment. PMID- 26556907 TI - Progression or Regression? - Strengths and Weaknesses of the New Munich Nomenclature III for Cervix Cytology. AB - Introduction: Since 01. 01. 2015 the new Munich nomenclature III for gynaecological diagnostics of the cervix has been in force. The changes have led to controversial scientific discussions. This study reports for the first time on the consequences. Materials and Methods: The present data are based on smear screening results for the year 2014. The data of 63 134 patients were evaluated. Results: 2.27 % of all smears were remarkable. Group IIa was assigned to 0.91 %. Group II-p was somewhat more frequently recorded than group IIID1 (0.59 vs. 0.53 %). Groups IIID1 and IIID2 were found in 0.53 and 0.61 %, respectively, of the cases. Agreement with histology was found in 36.84 and 44.68 %, respectively. Glandular lesions represented the most frequent changes in group III. Histological clarification was obtained for 0.18 % of all remarkable findings. The relative incidence of high-grade precancerous conditions (CIN III) and invasive tumours amounted to 0.1 %. Conclusion: A close communication between gynaecologists and cytologists is mandatory for the correct usage of the new nomenclature. The future annual statistics of the health insurances can now be analysed in more detail. A statistical classification of glandular epithelial changes is now also possible for the first time. The heterogeneous group IIa constitutes an unnecessary uncertainty for patients and physicians. The splitting of the group IIID does not appear to have any advantage for the further clinical management. Further studies are needed to show whether or not the classification can stand up to international comparisons. PMID- 26556908 TI - Relevance of HPV Screening for Triaging Equivocal Cytology Findings in the Pap II p, Pap III and Pap IIID Groups - Results of Two Long-Term Studies. AB - Introduction: The use of HPV screening for the triage of ASC-US (atypical squamous cells of undetermined significance) cytology results has been established as a sound standard by international trials whereas the data for other cytology findings are in part contradictory. There is a lack of long-term studies on the use of HPV triage in Germany. Materials and Methods: For the present study data from a primary HPV screening project involving women aged over 30 years, ongoing since 2006, and an epidemiological study on women aged between 20 and 27 years, ongoing since 2009, were used. Upon recruitment, all women underwent a smear test for cytology and screening for "high-risk" HPV using Hybrid Capture 2 (HC2). If both tests were positive or if there were persisting remarkable cytology findings or a positive HPV test, then clarification by colposcopy was performed. Results: Altogether, among 282 women with Pap II-p (ASC US), Pap III (ASC-H) or Pap IIID (LSIL + CIN2) and negative HPV test there was no case of CIN3+. Among the women under 30 years of age, however, 69 % (ASC-US) to 85 % (LSIL + CIN2) of the remarkable findings were HPV positive, also among the older women with Pap IIID, the 71 % prevalence of HPV was too high for a triage and even without triage there was a 23 % risk for CIN3+. On the other hand, of the women over 30 years old with ASC-US (Pap II-p) findings, only 21 % were positive for HPV and the risk for CIN3+ in this group was high at 29 %. Also for ASC-H (Pap III) findings in the age group of over 30 years with an HPV prevalence of 56 % there was an efficient triage for CIN3+. Discussion: In summary, the HPV triage of ASC-US (Pap II-p) findings in women aged over 30 years was found to be efficient; in contrast, LSIL + CIN2 (Pap IIID) findings in this age group justified an immediate referral to colposcopy whereas cytology control appeared to be sufficient for younger women. PMID- 26556909 TI - Conflicting Priorities in Social Legislation and Medicine: Gynaeco-oncology Patients and their Right to Participate in Society. AB - Due to the declining mortality rates, malignant diseases have gained a chronic character for many gynaeco-oncology patients. The patients can expect to participate in social life and to an increasing extent in professional life for longer lengths of time. Promotion of rehabilitation and participation is an issue of the German 9th Social Security Code that explicitly places a focus on women. This is mainly of relevance for tumour patients with regard to assessment of the degree of severe disability, to compensate for disease-induced impairments and the possibilities for improving the participation of the afflicted subjects, especially by means of protective rights in professional life. Indeed, tumour patients do sometimes find themselves confronted with conflicting priorities between the entitlements guaranteed by social legislation and the compensation conferred by the health-care services, which can then be avoided when the facts are sufficiently known. For this purpose, the physician must be fully aware of the legal situation. The present article provides an overview of the procedures and reference points for appraisals. Patients need partners among their responsible physicians to help in the assertion of their claims. From the physician's side it is necessary to classify the reported complaints within the ever increasing knowledge about the direct side effects and the long-term side effects of cancer therapies. Against the background of an often life-long mental stress and the uncertain risk of recurrence, it should also be considered whether the concept of healing probation is in support of the targets of long-term disease management and social reintegration, also in the interest of society in general. PMID- 26556910 TI - An Empirical Expression to Predict the Resonant Frequencies of Archimedean Spirals. AB - This work presents an empirical formula to accurately determine the frequencies of the fundamental and higher order resonances of an Archimedean spiral in a uniform dielectric medium in the absence of a ground plane. The formula is based on method-of-moments simulations which have been experimentally validated. This empirical formula is widely applicable to a broad range of spirals from thin-ring to disk-shaped (ratio of inner to outer radii 0 to 1), with 10 or more turns. PMID- 26556911 TI - Anatomy and physiology of respiratory system relevant to anaesthesia. AB - Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone. PMID- 26556912 TI - Pre-operative pulmonary evaluation in the patient with suspected respiratory disease. AB - Post-operative pulmonary complications (POPC) occur frequently, especially in patients with pre-existing pulmonary disease and have a significant effect on post-surgical morbidity and mortality. By understanding the patient's existing pulmonary diseases that have a significant effect on post-operative morbidities a combination of information has to be gathered from a thorough history and physical exam as well as selected laboratory and diagnostic tests. Evidence based scores can then be employed to predict the risk of significant POPC. Numbers and testing alone, however, such as diagnosis of chronic obstructive pulmonary disease based on spirometry, may not provide as clear a picture as of the true risk of POPC that is determined by a combination of estimations of the patient's functional status, (b) measured by the patient's estimates of activity and (c) confirmed by the patient's ability to perform simple tasks such as the 6-minute walk test. This information can then be used to rationalize perioperative interventions and improve the safety of the perioperative experience. PMID- 26556913 TI - Pre-operative optimisation of lung function. AB - The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4-6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function. PMID- 26556914 TI - Effects of anaesthesia techniques and drugs on pulmonary function. AB - The primary task of the lungs is to maintain oxygenation of the blood and eliminate carbon dioxide through the network of capillaries alongside alveoli. This is maintained by utilising ventilatory reserve capacity and by changes in lung mechanics. Induction of anaesthesia impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics. All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems. Volatile anaesthetic agents have more pronounced effects on pulmonary functions compared to intravenous induction agents, leading to hypercarbia and hypoxia. The posture of the patient also leads to major changes in pulmonary functions. Anticholinergics and neuromuscular blocking agents have little effect. Analgesics and sedatives in combination with volatile anaesthetics and induction agents may exacerbate their effects. Since multiple agents are used during anaesthesia, ultimate effect may be different from when used in isolation. Literature search was done using MeSH key words 'anesthesia', 'pulmonary function', 'respiratory system' and 'anesthesia drugs and lungs' in combination in PubMed, Science Direct and Google Scholar filtered by review and research articles sorted by relevance. PMID- 26556915 TI - Anaesthesia for bronchoscopy. AB - Bronchoscopy as an investigation or therapeutic procedure demands anaesthesiologist to act accordingly. The present review will take the reader from rigid to fibreoptic flexible bronchoscopy. These procedures are now done as day care procedures in the operation theatre or in critical care units. Advantages and limitations of both rigid and flexible bronchoscopy are analysed. Recently, conscious sedation has come up as the commonly used anaesthetic technique for simple bronchoscopic procedures. However, general anaesthesia still remains a standard technique for more complex procedures. New advances in the field of anaesthesiology such as use of short acting opioids, use of newer drugs such as dexmedetomidine, supraglottic airways and mechanical jet ventilators have facilitated and eased the conduct of the procedure. PMID- 26556916 TI - Anaesthesia for patient with chronic obstructive pulmonary disease. AB - The chronic obstructive pulmonary disease has become a disease of public health importance. Among the various risk factors, smoking remains the main culprit. In addition to airway obstruction, the presence of intrinsic positive end expiratory pressure, respiratory muscle dysfunction contributes to the symptoms of the patient. Perioperative management of these patients includes identification of modifiable risk factors and their optimisation. Use of regional anaesthesia alone or in combination with general anaesthesia improves pulmonary functions and reduces the incidence of post-operative pulmonary complications. PMID- 26556917 TI - Anaesthesia for children with bronchial asthma and respiratory infections. AB - Asthma represents one of the most common chronic diseases in children with an increasing incidence reported worldwide. The key to successful anaesthetic outcome involves thorough pre-operative assessment and optimisation of the child's pulmonary status. Judicious application of proper anti-inflammatory and bronchodilatory regimes should be instituted as part of pre-operative preparation. Bronchospasm triggering agents should be carefully probed and meticulously avoided. A calm and properly sedated child at the time of induction is ideal, so also is extubation in a deep plane with an unobstructed airway. Wherever possible, regional anaesthesia should be employed. This will avoid airway manipulations, with additional benefit of excellent peri-operative analgesia. Agents with a potential for histamine release and techniques that can increase airway resistance should be diligently avoided. Emphasis must be given to proper post-operative care including respiratory monitoring, analgesia and breathing exercises. PMID- 26556918 TI - Mechanical ventilation in patients with chronic obstructive pulmonary disease and bronchial asthma. AB - Chronic obstructive pulmonary disease (COPD) and bronchial asthma often complicate the surgical patients, leading to post-operative morbidity and mortality. Many authors have tried to predict post-operative pulmonary complications but not specifically in COPD. The aim of this review is to provide recent evidence-based guidelines regarding predictors and ventilatory strategies for mechanical ventilation in COPD and bronchial asthma patients. Using Google search for indexing databases, a search for articles published was performed using various combinations of the following search terms: 'Predictors'; 'mechanical ventilation'; COPD'; 'COPD'; 'bronchial asthma'; 'recent strategies'. Additional sources were also identified by exploring the primary reference list. PMID- 26556919 TI - Post-operative pulmonary complications after non-cardiothoracic surgery. AB - Post-operative pulmonary complications (PPCs) occur in 5-10% of patients undergoing non-thoracic surgery and in 22% of high risk patients. PPCs are broadly defined as conditions affecting the respiratory tract that can adversely influence clinical course of the patient after surgery. Prior risk stratification, risk reduction strategies, performing short duration and/or minimally invasive surgery and use of anaesthetic technique of combined regional with general anaesthesia can reduce the incidence of PPCs. Atelectasis is the main cause of PPCs. Atelectasis can be prevented or treated by adequate analgesia, incentive spirometry (IS), deep breathing exercises, continuous positive airway pressure, mobilisation of secretions and early ambulation. Pre operative treatment of IS is more effective. The main reason for post-operative pneumonia is aspiration along the channels formed by longitudinal folds in the high volume, low pressure polyvinyl chloride cuffs of the endotracheal tubes. Use of tapered cuff, polyurethane cuffs and selective rather than the routine use of nasogastric tube can decrease chances of aspiration. Acute lung injury is the most serious PPC which may prove fatal. PMID- 26556920 TI - Lung isolation, one-lung ventilation and hypoxaemia during lung isolation. AB - Lung isolation is being used more frequently in both adult and paediatric age groups due to increasing incidence of thoracoscopy and video-assisted thoracoscopic surgery in these patients. Various indications for lung isolation and one-lung ventilation include surgical and non-surgical reasons. Isolation can be achieved by double-lumen endotracheal tubes or bronchial blocker. Different issues arise in prone and semi-prone position. The management of hypoxia with lung isolation is a stepwise drill of adding inhaled oxygen, adding positive end expiratory pressure to ventilated lung and continuous positive airway pressure to non-ventilated side. PMID- 26556921 TI - Post-operative pulmonary complications after thoracotomy. AB - Pulmonary complications are a major cause of morbidity and mortality in the post operative period after thoracotomy. The type of complications and the severity of complications depend on the type of thoracic surgery that has been performed as well as on the patient's pre-operative medical status. Risk stratification can help in predicting the possibility of the post-operative complications. Certain airway complications are more prone to develop with thoracic surgery. Vocal cord injuries, bronchopleural fistulae, pulmonary emboli and post-thoracic surgery non cardiogenic pulmonary oedema are some of the unique complications that occur in this subset of patients. The major pulmonary complications such as atelectasis, bronchospasm and pneumonia can lead to respiratory failure. This review was compiled after a search for search terms within 'post-operative pulmonary complications after thoracic surgery and thoracotomy' on search engines including PubMed and standard text references on the subject from 2000 to 2015. PMID- 26556922 TI - Vetting and Letting: Cohabiting Stepfamily Formation Processes in Low-Income Black Families. AB - The authors examined cohabiting union formation processes by analyzing in-depth interview data collected from 30 individuals in cohabiting relationships: 15 low income Black mothers of adolescents and their partners. Prior research suggests that cohabiting union formation is a gradual, nondeliberative process. In contrast, most couples in this study described a gradual but highly deliberative process. Mothers focused primarily on vetting their partners to ensure child well being and less on when and how their partners officially came to live with them, a process the authors call vetting and letting. Mothers delineated 4 strategies to ensure their child's well-being when vetting their partners, and their partners reported that they understood the importance of participating in this process. The authors argue that vetting and letting is a child-centered family formation process, not a partner-centered union formation process, and that cohabiting union processes may vary substantially by subpopulation. PMID- 26556923 TI - A Message from the Editor. PMID- 26556924 TI - A Season of Hope, A Season of Action: Addressing Mental Health Through Faith Communities. PMID- 26556926 TI - The Hope Multipliers: the U.S. Public Health Service in Monrovia. PMID- 26556927 TI - Lessons Learned from the Diffusion of Effective Behavioral Interventions Program for Childhood Obesity Interventions. PMID- 26556928 TI - Classifying Infant Deaths with a Focus on Prevention Strategies. PMID- 26556929 TI - Assessing the State of Vaccine Confidence in the United States: Recommendations from the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on June 9, 2015 [corrected]. PMID- 26556930 TI - Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009-2010. AB - Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009-December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups. PMID- 26556931 TI - Estimating the Size and Cost of the STD Prevention Services Safety Net. AB - The Patient Protection and Affordable Care Act is expected to reduce the number of uninsured people in the United States during the next eight years, but more than 10% are expected to remain uninsured. Uninsured people are one of the main populations using publicly funded safety net sexually transmitted disease (STD) prevention services. Estimating the proportion of the uninsured population expected to need STD services could help identify the potential demand for safety net STD services and improve program planning. In 2013, an estimated 8.27 million people met the criteria for being in need of STD services. In 2023, 4.70 million uninsured people are expected to meet the criteria for being in need of STD services. As an example, the cost in 2014 U.S. dollars of providing chlamydia screening to these people was an estimated $271.1 million in 2013 and is estimated to be $153.8 million in 2023. A substantial need will continue to exist for safety net STD prevention services in coming years. PMID- 26556932 TI - The Youth Nonfatal Violent Injury Review Panel: An Innovative Model to Inform Policy and Systems Change. AB - Among young people in the United States, nonfatal violent injuries outnumber fatal violent injuries by 171 to 1. The Child Fatality Review Team (CFRT) is a well-established model for informing injury prevention planning. The CFRT's restricted focus on fatal injuries, however, limits its ability to identify opportunities to prevent violent reinjury and address issues unique to nonfatal violent injuries. We adapted the CFRT model to develop and implement a Youth Nonfatal Violent Injury Review Panel. We convened representatives from 23 agencies (e.g., police, housing, and education) quarterly to share administrative information and confidentially discuss cases of nonfatal violent injury. In this article, we describe the panel model and present preliminary data on participants' perceptions of the process. Although outcomes research is needed to evaluate its impacts, the Youth Nonfatal Violent Injury Review Panel offers an innovative, promising, and replicable model for interagency collaboration to prevent youth violence and its effects. PMID- 26556933 TI - Policy, Systems, and Environmental Approaches to Obesity Prevention: Translating and Disseminating Evidence from Practice. AB - To reduce obesity prevalence, public health practitioners are intervening to change health behaviors as well as the policies, systems, and environments (PSEs) that support healthy behaviors. Although the number of recommended PSE intervention strategies continues to grow, limited guidance is available on how to implement those strategies in practice. This article describes the University of North Carolina at Chapel Hill, Center for Training and Research Translation's (Center TRT's) approach to reviewing, translating, and disseminating practitioner developed interventions, with the goal of providing more practical guidance on how to implement PSE intervention strategies in real-world practice. As of August 2014, Center TRT had disseminated 30 practice-based PSE interventions. This article provides an overview of Center TRT's process for reviewing, translating, and disseminating practice-based interventions and offers key lessons learned during the nine years that Center TRT has engaged in this work. PMID- 26556935 TI - Infant Mortality: Development of a Proposed Update to the Dollfus Classification of Infant Deaths. AB - OBJECTIVE: Identifying infant deaths with common underlying causes and potential intervention points is critical to infant mortality surveillance and the development of prevention strategies. We constructed an International Classification of Diseases 10th Revision (ICD-10) parallel to the Dollfus cause of-death classification scheme first published in 1990, which organized infant deaths by etiology and their amenability to prevention efforts. METHODS: Infant death records for 1996, dual-coded to the ICD Ninth Revision (ICD-9) and ICD-10, were obtained from the CDC public-use multiple-cause-of-death file on comparability between ICD-9 and ICD-10. We used the underlying cause of death to group 27,821 infant deaths into the nine categories of the ICD-9-based update to Dollfus' original coding scheme, published by Sowards in 1999. Comparability ratios were computed to measure concordance between ICD versions. RESULTS: The Dollfus classification system updated with ICD-10 codes had limited agreement with the 1999 modified classification system. Although prematurity, congenital malformations, Sudden Infant Death Syndrome, and obstetric conditions were the first through fourth most common causes of infant death under both systems, most comparability ratios were significantly different from one system to the other. CONCLUSION: The Dollfus classification system can be adapted for use with ICD-10 codes to create a comprehensive, etiology-based profile of infant deaths. The potential benefits of using Dollfus logic to guide perinatal mortality reduction strategies, particularly to maternal and child health programs and other initiatives focused on improving infant health, warrant further examination of this method's use in perinatal mortality surveillance. PMID- 26556934 TI - A Model of Shared Mycobacteriology Testing Services: Lessons Learned. AB - OBJECTIVE: The need for public health laboratories (PHLs) to prioritize resources has led to increased interest in sharing diagnostic services. To address this concept for tuberculosis (TB) testing, the New York State Department of Health Wadsworth Center and the Rhode Island State Health Laboratories assessed the feasibility of shared services for the detection and characterization of Mycobacterium tuberculosis complex (MTBC). METHODS: We assessed multiple aspects of shared services including shipping, testing, reporting, and cost. Rhode Island State Health Laboratories shipped MTBC-positive specimens and isolates to Wadsworth Center. Average turnaround times were calculated and cost analysis was performed. RESULTS: Testing turnaround times were similar at both PHLs; however, the availability of conventional drug susceptibility testing (DST) results for Rhode Island primary specimens and isolates were extended by approximately four days of shipping time. An extended molecular testing panel was performed on every specimen submitted from Rhode Island State Health Laboratories to Wadsworth Center, and the total cost per specimen at Wadsworth Center was $177.12 less than at Rhode Island State Health Laboratories, plus shipping. Following a mid-study review, Wadsworth Center provided testing turnaround times for detection (same day), species determination of MTBC (same day), and molecular DST (2.5 days). CONCLUSION: The collaboration between Wadsworth Center and Rhode Island State Health Laboratories to assess shared services of TB testing highlighted a successful model that may serve as a guideline for other PHLs. The provision of additional rapid testing at a lower cost demonstrated in this study could potentially improve patient management and result in significant cost and resource savings if used in similar models across the country. PMID- 26556936 TI - Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged >= 40 Years: Data from the National Health and Nutrition Examination Survey, 2011 2012. AB - OBJECTIVE: We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. METHODS: We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged >= 40 years from the National Health and Nutrition Examination Survey, 2011-2012. RESULTS: In 2011-2012, one-third of U.S. adults aged >= 40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40-49 years to 54% of those >= 80 years of age, p<0.001). Non-Hispanic white (35%) and black (30%) adults were more likely to take preventive aspirin than non-Hispanic Asian (20%, p<0.001) and Hispanic (22%, p=0.013) adults. Adults with, compared with those without health insurance, and adults with >= 2 doctor visits in the past year, diagnosed diabetes, hypertension, or high cholesterol were twice as likely to take preventive aspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. CONCLUSION: The vast majority of antiplatelet therapy is preventive aspirin use. A health care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID- 26556937 TI - Zombie Apocalypse: Can the Undead Teach the Living How to Survive an Emergency? AB - OBJECTIVE: We examined whether or not CDC's zombie apocalypse campaign had the ability to achieve the agency's goals of educating young people about emergency preparedness and prompting them to get ready by developing an emergency kit and plan. While the campaign was extremely popular, we examined the question of whether the campaign had the capability to translate into knowledge and action. METHODS: We conducted an online experiment with 340 undergraduate students divided randomly into two groups. One group was exposed to CDC's zombie blog post; the other to the same preparedness information presented in CDC's traditional, straightforward way. Participants then completed a survey designed to gauge their affective feelings, perceptions, retention of preparedness preparation, and intent to develop an emergency kit and plan. RESULTS: While participants who viewed the humorous zombie material clearly enjoyed it, their positive affect did not lead to greater retention of preparedness information or greater expressed intent to prepare, compared with participants exposed to the factual treatment. The zombie approach had no influence on retention or resulted in less retention relative to the factual approach. Also, there was no significant between-group difference in reported likelihood of developing an emergency kit or plan. CONCLUSION: While the campaign drew unprecedented traffic to CDC's website, our findings suggest that it lacked the capability to fully achieve the agency's goals of educating people about preparedness and prompting them to get ready. This finding supports previous studies concluding that it is challenging to design public health messages that evoke positive affect as well as intended changes in intentions or behaviors. PMID- 26556938 TI - Household Debt and Relation to Intimate Partner Violence and Husbands' Attitudes Toward Gender Norms: A Study Among Young Married Couples in Rural Maharashtra, India. AB - OBJECTIVE: Evidence has linked economic hardship with increased intimate partner violence (IPV) perpetration among males. However, less is known about how economic debt or gender norms related to men's roles in relationships or the household, which often underlie IPV perpetration, intersect in or may explain these associations. We assessed the intersection of economic debt, attitudes toward gender norms, and IPV perpetration among married men in India. METHODS: Data were from the evaluation of a family planning intervention among young married couples (n=1,081) in rural Maharashtra, India. Crude and adjusted logistic regression models for dichotomous outcome variables and linear regression models for continuous outcomes were used to examine debt in relation to husbands' attitudes toward gender-based norms (i.e., beliefs supporting IPV and beliefs regarding male dominance in relationships and the household), as well as sexual and physical IPV perpetration. RESULTS: Twenty percent of husbands reported debt. In adjusted linear regression models, debt was associated with husbands' attitudes supportive of IPV (b=0.015, p=0.004) and norms supporting male dominance in relationships and the household (b=0.006, p=0.003). In logistic regression models adjusted for relevant demographics, debt was associated with perpetration of physical IPV (adjusted odds ratio [AOR] = 1.4, 95% confidence interval [CI] 1.1, 1.9) and sexual IPV (AOR=1.6, 95% CI 1.1, 2.1) from husbands. These findings related to debt and relation to IPV were slightly attenuated when further adjusted for men's attitudes toward gender norms. CONCLUSION: Findings suggest the need for combined gender equity and economic promotion interventions to address high levels of debt and related IPV reported among married couples in rural India. PMID- 26556939 TI - Association Between Neighborhood-Level Smoking and Individual Smoking Risk: Maternal Smoking Among Latina Women in Pennsylvania. AB - OBJECTIVE: We examined whether or not high maternal smoking rates at the neighborhood level increase the likelihood of individual smoking by Latina women in the three months prior to and during pregnancy, independent of other individual and neighborhood factors. METHODS: This study was observational in nature, using linked vital statistics records for 24,443 Latina women in Pennsylvania (2009-2010) and U.S. Census data for 2,398 census tracts. We used multilevel logistic regression models to determine the individual odds of self reported maternal smoking given different census tract-level rates of maternal smoking in the previous three years (2006-2008), adjusting for maternal and census-tract characteristics, including ethnic density, population density, and poverty. RESULTS: Higher levels of maternal smoking at the census-tract level were associated with increased individual odds of smoking among Latina mothers. In the fully adjusted model, a 10% increase in the neighborhood smoking rate was associated with a 1.28 (95% confidence interval 1.22, 1.34) increase in the individual odds of smoking. CONCLUSION: Latina women living in census tracts where more women have smoked during or immediately prior to pregnancy are themselves at higher risk of smoking during this period. PMID- 26556940 TI - Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening. AB - OBJECTIVE: This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementation. METHODS: We calculated the baseline annual frequency of homelessness and risk of homelessness among all veterans who completed an initial screen during the study period. We measured changes in housing status among veterans who initially screened positive and then completed a follow-up screen, assessed factors associated with such changes, and identified distinct risk profiles of veterans who completed a follow-up screen. RESULTS: More than 4 million veterans completed an initial screen; 1.8% (n=77,621) screened positive for homelessness or risk of homelessness. Of those who initially screened positive for either homelessness or risk of homelessness and who completed a second screen during the study period, 85.0% (n=15,060) resolved their housing instability prior to their second screen. Age, sex, race, VHA eligibility, and screening location were all associated with changes in housing stability. We identified four distinct risk profiles for veterans with ongoing housing instability. CONCLUSION: To address homelessness among veterans, efforts should include increased and targeted engagement of veterans experiencing persistent housing instability. PMID- 26556941 TI - Chronic Liver Disease-Associated Hospitalizations Among Adults with Diabetes, National Inpatient Sample, 2001-2012. AB - OBJECTIVE: Many people with diabetes have a variety of diabetes-related complications. Among the variety of conditions associated with diabetes, however, liver diseases are less well recognized. As such, we aimed to describe chronic liver disease (CLD)-associated hospitalization rates among U.S. adults with diabetes from 2001-2012. METHODS: We used a nationally representative database of hospitalizations, the National Inpatient Sample, to determine CLD-associated hospitalization rates among U.S. adults aged >= 18 years with and without diabetes, from 2001-2012. Hospitalizations listing an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for CLD on the discharge record were selected for analysis and were further classified by diabetes status based on concurrent presence of a diabetes ICD-9-CM code. We calculated average annual age-adjusted hospitalization rates and 95% confidence intervals (CIs), and conducted a test for trend. RESULTS: For 2001 2012, the total age-adjusted CLD-associated hospitalization rate among adults with diabetes (1,680.9 per 100,000 population; 95% CI 1,577.2, 1,784.6) was approximately four times the rate of adults without diabetes (424.2 per 100,000 population; 95% CI 413.4, 435.1). Total age-adjusted hospitalization rates of adults with and without diabetes increased 59% and 48%, respectively, from 2001 2002 to 2011-2012 (p<0.001). Hepatitis C- and chronic hepatitis and cirrhosis associated hospitalizations comprised the largest proportion of total CLD associated hospitalizations among adults with and without diabetes. CONCLUSION: Providers should be aware of the potential existence of CLD among adults with diabetes and counsel patients on preventive methods to avoid progressive liver damage. PMID- 26556942 TI - Effects of Economic Conditions and Organizational Structure on Local Health Jurisdiction Revenue Streams and Personnel Levels in Connecticut, 2005-2012. AB - OBJECTIVE: We investigated whether or not changes in economic conditions during the 2008-2010 U.S. recession were associated with changes in Connecticut local health jurisdictions' (LHJs') revenue or personnel levels. METHODS: We analyzed Connecticut Department of Public Health 2005-2012 annual report data from 91 Connecticut LHJs, as well as publicly available data on economic conditions. We used fixed- and random-effect regression models to test whether or not LHJ per capita revenues and full-time equivalent (FTE) personnel differed during and post recession compared with pre-recession, or varied with recession intensity, as measured by unemployment rates and housing permits. RESULTS: On average, total revenue per capita was significantly lower during and post-recession compared with pre-recession, with two-thirds of LHJs experiencing per capita revenue reductions. FTE personnel per capita were significantly lower post-recession. Changes in LHJ-level unemployment rates and housing permits did not explain the variation in revenue or FTE personnel per capita. Revenue and personnel differed significantly by LHJ organizational structure across all time periods. CONCLUSION: Economic downturns can substantially reduce resources available for local public health. LHJ organizational structure influences revenue levels and sources, with implications for the scope, quality, and efficiency of services delivered. PMID- 26556943 TI - Assessing the Practices of Population-Based Birth Defects Surveillance Programs Using the CDC Strategic Framework, 2012. AB - OBJECTIVE: We assessed the practices of U.S. population-based birth defects surveillance programs in addressing current and emergent public health needs. METHODS: Using the CDC Strategic Framework considerations for public health surveillance (i.e., lexicon and standards, legal authority, technological advances, workforce, and analytic capacity), during 2012 and 2013, we conducted a survey of all U.S. operational birth defects programs (n=43) soliciting information on legal authorities, case definition and clinical information collected, types of data sources, and workforce staffing. In addition, we conducted semi-structured interviews with nine program directors to further understand how programs are addressing current and emergent needs. RESULTS: Three quarters of birth defects surveillance programs used national guidelines for case definition. Most birth defects surveillance programs (86%) had a legislative mandate to conduct surveillance, and many relied on a range of prenatal, postnatal, public health, and pediatric data sources for case ascertainment. Programs reported that the transition from paper to electronic formats was altering the information collected, offering an opportunity for remote access to improve timeliness for case review and verification. Programs also reported the growth of pooled, multistate data collaborations as a positive development. Needs identified included ongoing workforce development to improve information technology and analytic skills, more emphasis on data utility and birth defects specific standards for health information exchange, and support to develop channels for sharing ideas on data interpretation and dissemination. CONCLUSION: The CDC Strategic Framework provided a useful tool to determine the birth defects surveillance areas with positive developments, such as multi-state collaborative epidemiologic studies, and areas for improvement, such as preparation for health information exchanges and workforce database and analytic skills. Our findings may inform strategic deliberations for enhancing the effectiveness of birth defects surveillance programs. PMID- 26556945 TI - King v. Burwell and Beyond: Implications for Public Health Policy and Practice. PMID- 26556947 TI - Underreporting of Melanoma in Arizona and Strategies for Increasing Reporting: A Public Health Partnership Approach. PMID- 26556948 TI - Complement Split Products in Amniotic Fluid in Pregnancies Subsequently Developing Early-Onset Preeclampsia. AB - OBJECTIVE: To determine the second-trimester amniotic fluid concentrations of complement split products in pregnancies subsequently affected by early-onset preeclampsia. STUDY DESIGN: Cohort of 731 women with singleton pregnancies undergoing second-trimester genetic amniocentesis followed up to delivery and analyzed as a nested case-control study. Cases of preeclampsia developing before 34 weeks' gestation (n = 15) were compared with 47 uncomplicated term controls. Amniotic fluid collected at amniocentesis was tested for complement split products Bb, C4a, C3a, and C5a. RESULTS: Women who developed early-onset preeclampsia as compared with the term pregnant controls had significantly higher (P = 0.04) median amniotic fluid C3a levels (318.7 ng/mL versus 254.5 ng/mL). Median amniotic fluid Bb levels were also significantly higher (P = 0.03) in preeclamptic women than in normal pregnant women (1127 ng/mL versus 749 ng/mL). Median levels of C4a and C5a were not significantly different between the groups. CONCLUSION: Our data suggest that complement activation in early pregnancy is associated with early-onset preeclampsia. We believe this to be the first prospective study to link complement activation in amniotic fluid in early pregnancy and later development of preeclampsia. Our findings provide evidence that immune dysregulation may precede the clinical manifestations of preeclampsia and that the alternative complement pathway is principally involved. PMID- 26556950 TI - Complexation Hydrogels as Oral Delivery Vehicles of Therapeutic Antibodies: An in Vitro and ex Vivo Evaluation of Antibody Stability and Bioactivity. AB - Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles. This contribution focuses on the design and evaluation of hydrogel carriers that will minimize the degradation and maximize the in vivo activity of anti-TNF-alpha, a mAb used for the treatment of inflammatory bowel disease (IBD) in the GI tract and systemically for the treatment of rheumatoid arthritis. P(MAA-g-EG) and P(MAA-co NVP) hydrogels systems were optimized to achieve adequate swelling behavior, which translated into improved protein loading and release at neutral pH simulating the small intestine conditions. Additionally, these hydrogel systems preserve antibody bioactivity upon release resulting in the systemic circulation of an antibody capable of effectively performing its biological function. The compatibility if these hydrogels for mAb bioactivity preservation and release makes them candidates for use as oral delivery systems for therapeutic antibodies. PMID- 26556949 TI - Prognostic Role of MicroRNA-200c-141 Cluster in Various Human Solid Malignant Neoplasms. AB - The miR-200 family has emerged recently as a noticeable marker for predicting cancer prognosis and tumor progression. We aimed to review the evidence of miR 200c-141 genomic cluster as prognostic biomarkers in cancers. The results suggested that high level of miR-200c had no significant impact on OS (HR = 1.14 [0.77-1.69], P = 0.501) and DFS/PFS (HR = 0.72 [0.45-1.14], P = 0.161). Stratified analyses revealed that high miR-200c expression was significantly related to poor OS in serum/plasma (HR = 2.12 [1.62-2.77], P = 0.000) but not in tissues (HR = 0.89 [0.58-1.37], P = 0.599). High miR-200c expression was significantly associated with favorable DFS/PFS in tissues (HR = 0.56 [0.43 0.73], P = 0.000) but worse DFS/PFS in serum/plasma (HR = 1.90 [1.08-3.36], P = 0.027). For miR-141, we found that high miR-141 expression predicted no significant impact on OS (HR = 1.18 [0.74-1.88], P = 0.482) but poor DFS/PFS (HR = 1.11 [1.04-1.20], P = 0.003). Similarly, subgroup analyses showed that high miR 141 expression predicted poor OS in serum/plasma (HR = 4.34 [2.30-8.21], P = 0.000) but not in tissues (HR = 1.00 [0.92-1.09], P = 0.093). High miR-141 expression was significantly associated with worse DFS/PFS in tissues (HR = 1.12 [1.04-1.20], P = 0.002) but not in serum/plasma (HR = 0.90 [0.44-1.83], P = 0.771). Our findings indicated that, compared to their tissue counterparts, the expression level of miR-200c and miR-141 in peripheral blood may be more effective for monitoring cancer prognosis. High miR-141 expression was better at predicting tumor progression than survival for malignant tumors. PMID- 26556951 TI - Sexual Functioning, Desire, and Satisfaction in Women with TBI and Healthy Controls. AB - Traumatic brain injury (TBI) can substantially alter many areas of a person's life and there has been little research published regarding sexual functioning in women with TBI. Methods. A total of 58 women (29 with TBI and 29 healthy controls) from Neiva, Colombia, participated. There were no statistically significant differences between groups in sociodemographic characteristics. All 58 women completed the Sexual Quality of Life Questionnaire (SQoL), Female Sexual Functioning Index (FSFI), Sexual Desire Inventory (SDI), and the Sexual Satisfaction Index (ISS). Results. Women with TBI scored statistically significantly lower on the SQoL (p < 0.001), FSFI subscales of desire (p < 0.05), arousal (p < 0.05), lubrication (p < 0.05), orgasm (p < 0.05), and satisfaction (p < 0.05), and the ISS (p < 0.001) than healthy controls. Multiple linear regressions revealed that age was negatively associated with some sexuality measures, while months since the TBI incident were positively associated with these variables. Conclusion. These results disclose that women with TBI do not fare as well as controls in these measures of sexual functioning and were less sexually satisfied. Future research is required to further understand the impact of TBI on sexual function and satisfaction to inform for rehabilitation programs. PMID- 26556952 TI - The Role of TOX in the Development of Innate Lymphoid Cells. AB - TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development. PMID- 26556954 TI - Chemical Hypoxia Brings to Light Altered Autocrine Sphingosine-1-Phosphate Signalling in Rheumatoid Arthritis Synovial Fibroblasts. AB - Emerging evidence suggests a role for sphingosine-1-phosphate (S1P) in various aspects of rheumatoid arthritis (RA) pathogenesis. In this study we compared the effect of chemical hypoxia induced by cobalt chloride (CoCl2) on the expression of S1P metabolic enzymes and cytokine/chemokine secretion in normal fibroblast like synoviocytes (FLS) and RAFLS. RAFLS incubated with CoCl2, but not S1P, produced less IL-8 and MCP-1 than normal FLS. Furthermore, incubation with the S1P2 and S1P3 receptor antagonists, JTE-013 and CAY10444, reduced CoCl2-mediated chemokine production in normal FLS but not in RAFLS. RAFLS showed lower levels of intracellular S1P and enhanced mRNA expression of S1P phosphatase 1 (SGPP1) and S1P lyase (SPL), the enzymes that are involved in intracellular S1P degradation, when compared to normal FLS. Incubation with CoCl2 decreased SGPP1 mRNA and protein and SPL mRNA as well. Inhibition of SPL enhanced CoCl2-mediated cytokine/chemokine release and restored autocrine activation of S1P2 and S1P3 receptors in RAFLS. The results suggest that the sphingolipid pathway regulating the intracellular levels of S1P is dysregulated in RAFLS and has a significant impact on cell autocrine activation by S1P. Altered sphingolipid metabolism in FLS from patients with advanced RA raises the issue of synovial cell burnout due to chronic inflammation. PMID- 26556955 TI - Efficacy and Safety of Ropivacaine Addition to Intrathecal Morphine for Pain Management in Intractable Cancer. AB - OBJECTIVE: Although intrathecal drug infusion has been commonly adopted for terminal cancer pain relief, its adverse effects have made many clinicians reluctant to employ it for intractable cancer pain. The objective of this study is to compare the efficacy and security of an intrathecal continuous infusion of morphine and ropivacaine versus intrathecal morphine alone for cancer pain. METHODS: Thirty-six cancer patients received either a continuous morphine (n = 19) or morphine and ropivacaine (n = 17) infusion using an intrathecal catheter through a subcutaneous port. Numerical Rating Scale (NRS) scores and the Barthel Index were analyzed. Adverse effects and complications on postoperative days 1, 3, 7, and 15 were also analyzed. RESULTS: All patients experienced pain relief. Compared to those who received morphine alone, patients receiving morphine and ropivacaine had significantly lower postoperative morphine requirements and higher Barthel Index scores on the 15th postsurgical day (P < 0.05). Patients receiving morphine and ropivacaine had lower NRS scores than patients receiving morphine alone on postoperative days 1, 3, 7, and 15 (P < 0.05). Negative postsurgical effects were similar in both groups. CONCLUSIONS: Morphine and ropivacaine administration through intrathecal access ports is efficacious and safe and significantly improves quality of life. PMID- 26556956 TI - Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma. AB - Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS >= 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID- 26556953 TI - Regulation of Endothelial Adherens Junctions by Tyrosine Phosphorylation. AB - Endothelial cells form a semipermeable, regulated barrier that limits the passage of fluid, small molecules, and leukocytes between the bloodstream and the surrounding tissues. The adherens junction, a major mechanism of intercellular adhesion, is comprised of transmembrane cadherins forming homotypic interactions between adjacent cells and associated cytoplasmic catenins linking the cadherins to the cytoskeleton. Inflammatory conditions promote the disassembly of the adherens junction and a loss of intercellular adhesion, creating openings or gaps in the endothelium through which small molecules diffuse and leukocytes transmigrate. Tyrosine kinase signaling has emerged as a central regulator of the inflammatory response, partly through direct phosphorylation and dephosphorylation of the adherens junction components. This review discusses the findings that support and those that argue against a direct effect of cadherin and catenin phosphorylation in the disassembly of the adherens junction. Recent findings indicate a complex interaction between kinases, phosphatases, and the adherens junction components that allow a fine regulation of the endothelial permeability to small molecules, leukocyte migration, and barrier resealing. PMID- 26556957 TI - Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain. AB - Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-alpha and IL-1beta in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain. PMID- 26556958 TI - Association of Metabolic Syndrome with the Adiponectin to Homeostasis Model Assessment of Insulin Resistance Ratio. AB - This study aimed at determining whether the adiponectin to HOMA-IR (A/H) ratio is associated with MetS and MetS components and comparing the diagnostic efficacy of adiponectin, HOMA-IR, and the A/H ratio in healthy, middle-aged participants. MetS was assessed in 1628 Kazakh participants (men, 768; women, 860). The associations between adiponectin, HOMA-IR, and the A/H ratio with the components of MetS and MetS were examined using logistic regression analysis and receiver operating characteristic (ROC) curves. Our results show that A/H ratio may be a better diagnostic marker for MetS than either HOMA-IR or adiponectin alone, and it may serve as an important biomarker to determine an increased risk for MetS in healthy middle-aged population. PMID- 26556959 TI - The Trend of CEACAM3 Blood Expression as Number Index of the CTCs in the Colorectal Cancer Perioperative Course. AB - Pathological stage seems to be the major determinant of postoperative prognosis of solid tumors, but additional prognostic determinants need to be better investigated. The most important tumor marker for colorectal cancer (CRC) is the cell-surface antigen, Carcinoembryonic Antigen (CEA), and its assessment is considered a valuable index of circulating tumor cells (CTCs). In this paper, CEACAM3 evaluation was applied given its great specificity in the CRC. Whole blood from the basilic vein of 38 CRC patients was collected before and at various time intervals after the curative resection. Also, from 20 of them, we have obtained two additional intraoperative samples. CEACAM3 expression was evaluated in all the samples by RT-PCR. CEACAM3 duct values showed a decreasing trend from preoperative through early and later postoperative to 6th-month samples (p < 0.001). The average values of CEACAM3 were related to the cancer size (T stage) (p = 0.034) and WHO stage (p = 0.035). A significant effect of the baseline value of CEACAM3 dCt on the temporal trend has been observed (p < 0.001). In this study, we have demonstrated the CEACAM3 specificity and a perioperative trend of CTCs which is coherent with the clinical/pathological considerations and with previous experimental findings in different cancer types. PMID- 26556960 TI - The Fourth Law of Behavior Genetics. AB - Behavior genetics is the study of the relationship between genetic variation and psychological traits. Turkheimer (2000) proposed "Three Laws of Behavior Genetics" based on empirical regularities observed in studies of twins and other kinships. On the basis of molecular studies that have measured DNA variation directly, we propose a Fourth Law of Behavior Genetics: "A typical human behavioral trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioral variability." This law explains several consistent patterns in the results of gene discovery studies, including the failure of candidate gene studies to robustly replicate, the need for genome-wide association studies (and why such studies have a much stronger replication record), and the crucial importance of extremely large samples in these endeavors. We review the evidence in favor of the Fourth Law and discuss its implications for the design and interpretation of gene-behavior research. PMID- 26556961 TI - A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening. AB - New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development. PMID- 26556962 TI - Universal heart coverage for children with heart disease in India. PMID- 26556963 TI - Assessment and feasibility of the four landmarks of the aortic root in a cohort of very preterm infants. AB - BACKGROUND: The diameter of the aortic root is used as a parameter to calculate blood flow in very preterm infants. There are considerable differences in diameter of the four anatomical landmarks of the aortic root in children and adults, but limited data are available for the very preterm population. The aim of this study was to obtain reference and reliability data on two-dimensional measurements of the aortic root in very preterm infants <30 weeks gestation. MATERIALS AND METHODS: Fifty long axis echocardiograms were reviewed and re analyzed for measurements at the four anatomical landmarks of the aortic root; the aortic annulus, sinus of Valsalva (SV), sinotubular junction, and the proximal ascending aorta (PAA). A subjective visual scoring system was developed to quantify image quality. A random sample of images was blindly re-measured to assess intra- and inter-observer reliability. RESULTS: Significant differences in diameter were found between the four landmarks, except between SV and PAA. Inter observer coefficients showed marginal variation ranging from 5.0% to 8.2%, with slightly lower intra-observer variability. Overall image quality score was poorest for PAA on standard long axis images but improved when the probe was adjusted along the outflow tract. CONCLUSION: We present reliability and reference values for all four anatomic landmarks of the aortic root in very preterm infants and demonstrated the importance of standardizing and reporting cardiac output measurements in preterm infants. PMID- 26556964 TI - A novel snare assistance safeguards against early embolization of devices and facilitates quick retrieval of malpositioned devices in atrial septal defects with deficient margins. AB - BACKGROUND: Embolization might complicate device closure of large atrial septal defects (ASDs) with deficient margins. When margins are deficient, a precariously placed device can appear to be held in good position by the rigid delivery cable. Once the cable is unscrewed, the device adopts the natural lie of the interatrial septum. This can occasionally expose the inadequately captured margins and lead to device embolization. Most embolizations occur immediately after release. Retrieval of the embolized device required prolonged fluoroscopy and sometimes open heart surgery. OBJECTIVE: To evolve a new strategy of retrieval of a malpositioned device after unscrewing the cable before impending embolization. MATERIALS AND METHODS: After deploying the device in place, a snare is passed through the delivery sheath around the cable to grip the screw on the right atrial disc of the device. With the snare holding the screw end, the device is released by unscrewing the cable. The device position is reconfirmed on echocardiography. The snare is subsequently removed if the device was stable. In case of device migration, the same snare is used to retrieve the device before it embolizes completely. RESULTS: Snare assistance was used in 24 patients considered as high-risk for device embolization. Its usefulness was demonstrated in two patients with deficient posterior margin and small inferior margin where the device got malpositioned immediately after release. As the snare was still holding on to the screw end, the device could be retrieved into the sheath easily. CONCLUSION: This novel snare assisted device release strategy safeguards against device embolization in large ASDs with deficient rims and allows simplified retrieval. PMID- 26556966 TI - Endomyocardial fibrosis in Sub Saharan Africa: The geographical origin, socioeconomic status, and dietary habits of cases reported in Yaounde, Cameroon. AB - BACKGROUND: Endomyocardial fibrosis (EMF) is a neglected heart condition of the inter-tropical regions. Numerous hypotheses suggest a relationship between its geographical distribution in the affected regions and other etio-pathogenic factors such as dietary habits, infectious causes, and geochemical causes. Knowledge of its epidemiology in Cameroon remains limited, which is why we decided to describe the profile of a paediatric series of EMF in Yaounde. PATIENTS AND METHODS: A retrospective study was carried out on EMF in 54 patients diagnosed from 1 January 2006-31 December 2014 in a Paediatric Centre of Yaounde. Diagnosis was mainly echocardiographic. We compiled data on the geographic origins of the patients, their dietary habits and the socioeconomic profile of their families. RESULTS: The patients' ages ranged from 2 to 17 years, most of whom (83.3%) were between 5 and 15 years. For geographical distribution, all came from three tropical forest zones where they have lived since their childhood. These were Center (32/54), South (12/54), and East (10/54). All families had a moderate income, consumed tubers at least twice a week especially cassava (43/54) and had low sources of proteins. CONCLUSION: Apart from geographical similarities all patients of our series shared the same dietary habits. Our study was conducted in a hospital setting; therefore a screening of the disease in the whole national territory would enable a more reliable mapping. PMID- 26556965 TI - Percutaneous closure of patent arterial ducts in patients from high altitude: a sub-Saharan experience. AB - BACKGROUND: At high altitude, patent arterial ducts tend to be larger and associated with pulmonary hypertension. Patent ductus arteriosus device closure in this background could be challenging. OBJECTIVES: We report our experience with percutaneous closure of patent arterial ducts using a variety of devices in patients residing in a high altitude. PATIENTS AND METHODS: This is a retrospective review of the case records of 145 patients (age 9 months-20 years, mean 5.6 +/- 3.9 years, and weight 7-54 kg, mean 17.7 +/- 9.4) with duct sizes ranging between 2 and 21 mm, (mean, 5.8 +/- 2.7) who underwent percutaneous closure of patent arterial ducts. One hundred thirty-six (93.8%) of the patients were from a geographic area of 2100-2800 m above sea level. RESULTS: Successful device closure was achieved in 143 cases. It was difficult to achieve device stability in two patients with expansile ducts. Therefore, they were treated surgically. The devices used were various types of duct occluder devices in 131 patients, while atrial and ventricular septal occluders were used in eight patients. For the group, mean systolic pulmonary artery (PA) pressure decreased from 47.0 +/- 16.7 mmHg before occlusion to 29.0 +/- 7.4 mmHg after occlusion (P <= 0.001)., mean diastolic PA pressure from 25.0 +/- 10.9 mmHg to 14.8 +/- 6.0 mmHg and the average mean PA pressure decreased from 35.9 +/- 13.5 mmHg to 21.1 +/- 6.5 mmHg. Complications (4.8%) included device and coil embolization, bleeding, and pulse loss. On follow-up (mean duration of 36.1 +/- 12.1 months, range 12-62 months), 137 patients were in functional class 1, 3 had residual shunt, 2 had device migration and one patient had persisting pulse loss. CONCLUSIONS: Successful duct closure was achieved in the vast majority of patients, even though the ducts were larger and significant number of them had pulmonary hypertension in this high altitude group. There was a relatively higher incidence of residual shunts and device migration in this series, generally due to the nonavailability of optimal device and surgical support. Long-term follow up is required before we can draw conclusions with regard to the sustainability of drop in PA pressures. Septal Occluder devices may be a possible alternative for large tubular or window-type ducts with severe pulmonary hypertension, where there may be concerns about the size and stability of duct occluder devices. PMID- 26556968 TI - Transcatheter closure of patent vertical vein after repair of total anomalous pulmonary venous connection. AB - BACKGROUND: Vertical vein is left patent in some cases of supra-cardiac total anomalous pulmonary venous connection (TAPVC) when there is hemodynamic instability due to noncompliant left atrium and ventricle. After the peri operative period, this results in features of pre-tricuspid shunt. MATERIALS AND METHODS: Three cases with patent vertical vein following repair of supra-cardiac TAPVC presented with features of pre-tricuspid shunt on follow-up. Trans-catheter closure of patent vertical vein was performed using vascular plug in all three subjects. RESULTS: The procedure was technically successful in all the patients. There was a complication related to catheter tip breakage in one of them, which was successfully managed. There was no impingement on pulmonary vein in any of the patients. CONCLUSION: Patent vertical vein following TAPVC repair results in features of pre-tricuspid shunt. Transcatheter closure of the patent vein is feasible. PMID- 26556967 TI - Inherited arrhythmias: The cardiac channelopathies. AB - Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms "Long QT Syndrome" (MeSH) and "Short QT Syndrome" (MeSH) and "Brugada Syndrome" (MeSH) and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID- 26556969 TI - Acute endocarditis of a percutaneously placed pulmonary valve. AB - Endocarditis of percutaneously placed pulmonary valve is increasingly being recognized and reported as a potentially life-threatening complication. In this report, we discuss a 17-year-old male who presented with septic shock secondary to staphylococcal endocarditis of a percutaneously placed pulmonary valve. PMID- 26556970 TI - "Classical Blalock-Taussig shunt" gone wrong: Confusing the right common carotid with right subclavian artery. AB - A 14-year-old girl underwent classical Blalock-Taussig shunt at 5 months of age. Computed tomography evaluation showed "Adachi type H" pattern of aortic arch vessels with the right common carotid artery being anastomosed to the right pulmonary artery mistaking it for the right subclavian artery. PMID- 26556971 TI - Percutaneous tricuspid valve replacement in childhood. AB - Percutaneous replacement of the tricuspid valve with a bovine jugular venous valve (melody valve) was successfully undertaken in a 9-year-old boy. The patient had a previous history of bacterial endocarditis of the native tricuspid valve in infancy. Initially, a pericardial patch valve was created, followed by surgical replacement of the valve using a biological tissue valve at 4 years of age. Progressive stenosis and regurgitation of the biological valve, with severe venous congestion and resulting hepatic dysfunction prompted percutaneous valve replacement. PMID- 26556972 TI - Clarifying the atrioventricular junctional anatomy in the setting of double outlet right atrium. AB - Double outlet atrium is a rare cardiac anomaly wherein one of the atriums, most frequently the right atrium, opens into both the ventricles. Although seen more commonly in the setting of atrioventricular septal defect, this arrangement can also be found when one of the atrioventricular connections is atretic due to absence of the atrioventricular connection and the other atrioventricular valve straddles the muscular ventricular septum. It is the specific anatomy and connections of the atrioventricular junction that clarifies the situation and distinguishes between these two types of double outlet atrium. In this report, we present a case of double outlet right atrium co-existing with the absence of left atrioventricular connection. We then discuss the morphologic aspects of this interesting anomaly. PMID- 26556973 TI - Neurogenic stunned myocardium associated with pediatric brain tumor may not be catecholamine-induced. AB - A rare case of pediatric neurogenic stunned myocardium (NSM) associated with a brain tumor is reported. A previously healthy 6-year-old boy presented with coma, and imaging studies revealed a brain tumor. On hospitalization day 3, he developed NSM and neurogenic pulmonary edema necessitating intensive cardiopulmonary support. Although blood marker levels of cardiac injury were elevated, his plasma and urinary norepinephrine levels were within normal limits. His cardiorespiratory functions markedly improved by hospitalization day 8. This case report may be one of the first to document plasma and urinary catecholamine levels in pediatric NSM. While solid conclusion cannot be drawn based on experience from a single case, these results suggest that pediatric NSM may not be catecholamine-induced. PMID- 26556974 TI - Use of echocardiographic subxiphoid five-sixth area length (bullet) method in evaluation of adequacy of borderline left ventricle in hypoplastic left heart complex. AB - Indexed left ventricular end-diastolic volume (ILVEDV) is commonly used in evaluating "borderline left ventricle (LV)" in hypoplastic left heart complex (HLHC) to determine if the LV can sustain adequate systemic cardiac output. Commonly used quantification methods include biplane Simpson or the traditional five-sixth area length "bullet" methods, which have been shown to underestimate true LV volumes, when septal position is mildly abnormal. Subxiphoid five-sixth area length method is proposed as a more accurate estimate of true LV volume in the evaluation of borderline LV. PMID- 26556975 TI - Plastic bronchitis. AB - Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding. PMID- 26556976 TI - Demonstration of circular shunt in fetal Ebstein anomaly. AB - Ebstein's anomaly was diagnosed in a fetus at 24 weeks of gestation. There was significant cardiomegaly and severe tricuspid regurgitation (TR). There was functional pulmonary atresia with severe pulmonary regurgitation (PR) and this was causing a circular shunt. There was no fetal hydrops. PMID- 26556977 TI - Pacemaker lead design masquerading as lead fracture. AB - Performing chest X-ray is an important annual investigation to check pacemaker lead integrity during follow-up of patients with pacemakers. Understanding lead design is vital to the correct interpretation of X-rays to prevent inappropriate interventions for patients as highlighted in this case. PMID- 26556978 TI - An adult with central cyanosis and differential pulmonary vascularity. AB - A 22-year-old male patient presented with progressive effort intolerance of 2 years duration. Clinical findings and investigations were suggestive of Tetralogy of Fallot (TOF). In addition, there was a conspicuous difference in the pulmonary vascularity with oligemia on the left side and relative hypervascularity on the right side. The right pulmonary artery was arising from the proximal ascending aorta and the main pulmonary artery was continuing as the left pulmonary artery. The anomalous origin of a branch pulmonary artery from the aorta (AOPA) is a rare cardiac anomaly. We report this condition in association with TOF, highlighting the differential pulmonary vascularity. PMID- 26556979 TI - Surgical correction of obstructed total anomalous pulmonary venous return soon after birth. PMID- 26556980 TI - The future of Ross procedure. PMID- 26556981 TI - Hepatic metastases from gastric cancer: A surgical perspective. AB - Management of patients with hepatic metastases as the sole metastatic site at diagnosis of gastric cancer (synchronous setting) or detected during follow-up (metachronous) is controversial. The prevailing attitude in these cases is passive, leading to surgical palliation and, possibly, to chemotherapy. Authors focused this editorial in order to promote a more pragmatic attitude. They stress the importance of recognizing the good candidates to curative surgery of both gastric cancer and hepatic metastases (synchronous setting) or hepatic disease alone (metachronous disease) from those who will not benefit from surgical therapy. In fact, in adequately selected subgroup of patients surgery, especially if integrated in multimodal therapeutic strategies, may achieve unexpected 5-year survival rates, ranging from 10% to 40%. The critical revision of the literature suggests that some simple clinical criteria exist that may be effectively employed in patients selection. These are mainly related to the gastric cancer (factors T, N, G) and to the extent of hepatic involvement (factor H). Upon these criteria it is possible to adequately select about 50% of cases. In the remaining 50% of cases a critical discussion on a case-by-case basis is recommended, considering that among these patients some potential long-survivors exist, that survival is strictly influenced by the ablation of the tumor bulk and by multimodality treatments including chemotherapy and that in expert institutions this kind of surgery is performed with very low mortality and morbidity rates. PMID- 26556982 TI - Immunomodulating effects of antibiotics used in the prophylaxis of bacterial infections in advanced cirrhosis. AB - The use of norfloxacin either as primary or secondary prophylaxis of bacterial infections in advanced cirrhosis has improved patient's survival. This may be explained not only due to a significant decrease in the number of infections, but also because of a direct immunomodulatory effect. Selective intestinal decontamination with norfloxacin reduces translocation of either viable bacteria or bacteria-driven products from the intestinal lumen. In addition, norfloxacin directly modulates the systemic inflammatory response. The pro-inflammatory cytokine profile secreted by neutrophils from these patients shows a close, significant, and inverse correlation with serum norfloxacin levels. Similar effects have been described with other quinolones in different clinical conditions. Although the underlying mechanisms are not well defined for most of the antibiotics, the pathways triggered for norfloxacin to induce such immunomodulatory effects involve the down-regulation of pro-inflammatory inducible nitric oxide synthase, cyclooxygenase-2, and NF-kappaB and the up regulation of heme-oxygenase 1 and IL-10 expression. The knowledge of these immunomodulatory effects, additional to their bactericidal role, improves our comprehension of the interaction between antibiotics and the cellular host response and offer new possibilities for the development of new therapeutic strategies to manage and prevent bacterial infections in cirrhosis. PMID- 26556983 TI - Cirrhotic cardiomyopathy. AB - During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e' ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID- 26556985 TI - Ultrasound-based elastography for the diagnosis of portal hypertension in cirrhotics. AB - Progressive fibrosis is encountered in almost all chronic liver diseases. Its clinical signs are diagnostic in advanced cirrhosis, but compensated liver cirrhosis is harder to diagnose. Liver biopsy is still considered the reference method for staging the severity of fibrosis, but due to its drawbacks (inter and intra-observer variability, sampling errors, unequal distribution of fibrosis in the liver, and risk of complications and even death), non-invasive methods were developed to assess fibrosis (serologic and elastographic). Elastographic methods can be ultrasound-based or magnetic resonance imaging-based. All ultrasound-based elastographic methods are valuable for the early diagnosis of cirrhosis, especially transient elastography (TE) and acoustic radiation force impulse (ARFI) elastography, which have similar sensitivities and specificities, although ARFI has better feasibility. TE is a promising method for predicting portal hypertension in cirrhotic patients, but it cannot replace upper digestive endoscopy. The diagnostic accuracy of using ARFI in the liver to predict portal hypertension in cirrhotic patients is debatable, with controversial results in published studies. The accuracy of ARFI elastography may be significantly increased if spleen stiffness is assessed, either alone or in combination with liver stiffness and other parameters. Two-dimensional shear-wave elastography, the ElastPQ technique and strain elastography all need to be evaluated as predictors of portal hypertension. PMID- 26556984 TI - Inflammatory status in human hepatic cirrhosis. AB - This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis. PMID- 26556986 TI - Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico. AB - Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID- 26556987 TI - Non-invasive diagnosis of liver fibrosis and cirrhosis. AB - The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future. PMID- 26556988 TI - Do vasopressin V2 receptor antagonists benefit cirrhotics with refractory ascites? AB - Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal capacity to eliminate solute-free water and is considered to be related to persistent secretion of vasopressin despite low serum osmolality. This nonosmotic release of vasopressin is mediated by the autonomic nervous system, which senses the underfilling of arterial vascular component. This reduction of effective arterial blood volume is closely related to the development of ascites. Although the short-time effects of vasopressin V2 receptor antagonists (vaptans) on hyponatremia and ascites have been repeatedly reported, their effects on the long-term management of cirrhotic ascites have not been established yet. Considering that their effects on water diuresis and their safety are limited by severe underfilling state of patients, cautious approaches with adequate monitoring are needed to advanced cirrhosis. Proper indication, adequate doses and new possibility of combination therapy should be explored in the future controlled study. As hyponatremia is frequent obstacle to ascites management, judicious combination with low-dose diuretics may decrease the incidence of refractory ascites. Although vaptans show much promise in the treatment of advanced cirrhosis, the problem of high cost should be solved for the future. PMID- 26556989 TI - Gut microbiota and host metabolism in liver cirrhosis. AB - The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. PMID- 26556990 TI - Towards curative therapy in gastric cancer: Faraway, so close! AB - Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer (GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments. PMID- 26556991 TI - Second-line treatment of metastatic gastric cancer: Current options and future directions. AB - Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed. PMID- 26556992 TI - Emerging blood-based biomarkers for detection of gastric cancer. AB - Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality, and for improving the management of patients with gastric cancer (GC). Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for population-wide or risk group-based screening programs, while circulating biomarkers that reflect the genetic make-up and dynamics of the tumor would allow monitoring of treatment efficacy, predict recurrences and assess the genetic heterogeneity of the tumor. Recent research to identify blood-based biomarkers of GC has resulted in the identification of a wide variety of cancer-associated molecules, including various proteins, autoantibodies against tumor associated antigens, cell-free DNA fragments, mRNAs and various non-coding RNAs, circulating tumor cells and cancer derived extracellular vesicles. Each type of these biomarkers provides different information on the disease status, has different advantages and disadvantages, and distinct clinical usefulness. In the current review, we summarize the recent developments in blood-based GC biomarker discovery, discuss the origin of various types of biomarkers and their clinical usefulness and the technological challenges in the development of biomarker assays for clinical use. PMID- 26556994 TI - Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer. AB - The mortality rate of gastric cancer worldwide is as high as 70%, despite the development of novel therapeutic strategies. One reason for the high mortality is the rapid and uninhibited spread of the disease, such that the majority of patients are diagnosed at a stage when efficient therapeutic treatment is not available. Therefore, in-depth research is needed to investigate the mechanism of gastric cancer metastasis and invasion to improve outcomes and provide biomarkers for early diagnosis. The mitogen-activated protein kinase (MAPK) signaling pathway is widely expressed in multicellular organisms, with critical roles in multiple biological processes, such as cell proliferation, death, differentiation, migration, and invasion. The MAPK pathway typically responds to extracellular stimulation. However, the MAPK pathway is often involved in the occurrence and progression of cancer when abnormally regulated. Many studies have researched the relationship between the MAPK signaling pathway and cancer metastasis and invasion, but little is known about the important roles that the MAPK signaling pathway plays in gastric cancer. Based on an analysis of published data, this review aims to summarize the important role that the MAP kinases play in the invasion and metastasis of gastric cancer and attempts to provide potential directions for further research and clinical treatment. PMID- 26556993 TI - Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions. AB - Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available. PMID- 26556995 TI - Competing endogenous RNA networks and gastric cancer. AB - Recent studies have showed that RNAs regulate each other with microRNA (miRNA) response elements (MREs) and this mechanism is known as "competing endogenous RNA (ceRNA)" hypothesis. Long non-coding RNAs (lncRNAs) are supposed to play important roles in cancer. Compelling evidence suggests that lncRNAs can interact with miRNAs and regulate the expression of miRNAs as ceRNAs. Several lncRNAs such as H19, HOTAIR and MEG3 have been found to be associated with miRNAs in gastric cancer (GC), generating regulatory crosstalk across the transcriptome. These MRE sharing elements implicated in the ceRNA networks (ceRNETs) are able to regulate mRNA expression. The ceRNA regulatory networks including mRNAs, miRNAs, lncRNAs and circular RNAs may play critical roles in tumorigenesis, and the perturbations of ceRNETs may contribute to the pathogenesis of GC. PMID- 26556996 TI - Colitis-associated colon cancer: Is it in your genes? AB - Colitis-associated colorectal cancer (CA-CRC) is the cause of death in 10%-15% of inflammatory bowel disease (IBD) patients. CA-CRC results from the accumulation of mutations in intestinal epithelial cells and progresses through a well characterized inflammation to dysplasia to carcinoma sequence. Quantitative estimates of overall CA-CRC risks are highly variable ranging from 2% to 40% depending on IBD severity, duration and location, with IBD duration being the most significant risk factor associated with CA-CRC development. Recently, studies have identified IBD patients with similar patterns of colonic inflammation, but that differ with respect to CA-CRC development, suggesting a role for additional non-inflammatory risk factors in CA-CRC development. One suggestion is that select IBD patients carry polymorphisms in various low penetrance disease susceptibility genes, which pre-dispose them to CA-CRC development, although these loci have proven difficult to identify in human genome-wide association studies. Mouse models of CA-CRC have provided a viable alternative for the discovery, validation and study of individual genes in CA-CRC pathology. In this review, we summarize the current CA-CRC literature with a strong focus on genetic pre-disposition and highlight an emerging role for mouse models in the search for CA-CRC risk alleles. PMID- 26556997 TI - Transanal total mesorectal excision: A valid option for rectal cancer? AB - Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision (TaTME) might offer technical advantages over laparoscopic or open approaches particularly for tumors in the distal third of the rectum. The aim of this article is to review the current experience with TaTME. The limits and future developments are also explored. Although the experience with TaTME is still limited, it might be a promising alternative to laparoscopic TME, especially for difficult cases where laparoscopy is too demanding. The preliminary data on complications and short-term oncological outcomes are good, but also emphasize the importance of careful patient selection. Finally, there is a need for large-scale trials focusing on long-term outcomes and oncological safety before widespread adoption can be recommended. PMID- 26556999 TI - Neuroendocrine differentiation: The mysterious fellow of colorectal cancer. AB - Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer. PMID- 26557000 TI - Eicosanoid pathway in colorectal cancer: Recent updates. AB - Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis. PMID- 26556998 TI - Non-coding landscapes of colorectal cancer. AB - For two decades Vogelstein's model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy. PMID- 26557001 TI - Colorectal cancer: Metastases to a single organ. AB - Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. PMID- 26557002 TI - Pathophysiological mechanisms of death resistance in colorectal carcinoma. AB - Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors. PMID- 26557003 TI - Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update. AB - Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient's quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient's outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient's compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer. PMID- 26557004 TI - Laparoscopic sleeve gastrectomy: More than a restrictive bariatric surgery procedure? AB - Sleeve gastrectomy (SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications. PMID- 26557005 TI - Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis. AB - Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE. PMID- 26557006 TI - Role of oats in celiac disease. AB - A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with this condition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of gluten-free ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet. PMID- 26557007 TI - Preoperative endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors, including magnifying endoscopy. AB - Superficial non-ampullary duodenal epithelial tumor (SNADET) is defined as a sporadic tumor that is confined to the mucosa or submucosa that does not arise from Vater's papilla, and it includes adenoma and adenocarcinoma. Recent developments in endoscopic technology, such as high-resolution endoscopy and image-enhanced endoscopy, may increase the chances of detecting SNADET lesions. However, because SNADET is rare, little is known about its preoperative endoscopic diagnosis. The use of endoscopic resection for SNADET, which has no risk of metastasis, is increasing, but the incidence of complications, such as perforation, is significantly higher than in any other part of the digestive tract. A preoperative diagnosis is required to distinguish between lesions that should be followed up and those that require treatment. Retrospective studies have revealed certain endoscopic findings that suggest malignancy. In recent years, several new imaging modalities have been developed and explored for real time diagnosis of these lesion types. Establishing an endoscopic diagnostic tool to differentiate between adenoma and adenocarcinoma in SNADET lesions is required to select the most appropriate treatment. This review describes the current state of knowledge about preoperative endoscopic diagnosis of SNADETs, such as duodenal adenoma and duodenal adenocarcinoma. Newer endoscopic techniques, including magnifying endoscopy, may help to guide these diagnostics, but their additional advantages remain unclear, and further studies are required to clarify these issues. PMID- 26557008 TI - Endosonography guided management of pancreatic fluid collections. AB - The revised Atlanta classification of acute pancreatitis was adopted by international consensus, and is based on actual local and systemic determinants of disease severity. The local determinant is pancreatic necrosis (sterile or infected), and the systemic determinant is organ failure. Local complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors manually applied pre defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development and regulatory approval of improved and novel endoscopic devices specifically designed for transmural drainage of fluid and necrotic debris (access and patency devices), the authors predict continuing evolution in the management of PFCs. We believe that EUS will become an indispensable part of procedures used to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging methods or EUS. Finally, the authors propose an algorithm for managing fluid collections based on their size, location, associated symptoms, internal echogenic patterns, and content. PMID- 26557009 TI - Animal models of human colorectal cancer: Current status, uses and limitations. AB - AIM: To make orthotopic colon cancer murine models a more clearly understood subject. The orthotopic tumor models have been found to be more relevant in replicating the human disease process as compared to heterotopic models, many techniques for making orthotopic colorectal murine models have been reported. METHODS: We evaluated the current literature for various reported orthotopic colon cancer models to understand their techniques, advantages and limitations. An extensive literature review was performed by searching the National Library of Medicine Database (PubMed) using MeSH terms animal model; colon cancer; orthotopic model; murine model. Twenty studies related to colon cancer orthotopic xenograft model were evaluated in detail and discussed here. RESULTS: The detailed analysis of all relevant reports on orthotopic model showed tumor take rate between 42%-100%. While models using the enema technique and minimally invasive technique have reported development of tumor from mucosa with tumor take rate between 87%-100% with metastasis in 76%-90%. CONCLUSION: Over the years, the increased understanding of the murine models of human colon cancer has resulted in the development of various models. Each reported model has some limitations. These latest models have opened up new doors for continuing cancer research for not only understanding the colon cancer pathogenesis but also aid in the development of newer chemotherapeutic drugs as they mimic the human disease closely. PMID- 26557011 TI - Nomograms for colorectal cancer: A systematic review. AB - AIM: To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinical practice. METHODS: We conducted electronic searches for journal articles on colorectal cancer (CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed. RESULTS: We discuss the currently available CRC-associated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms. CONCLUSION: The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice. PMID- 26557012 TI - Prevalence of mental health problems and service use among first-time juvenile offenders. AB - It is known that youth engaged in the juvenile justice system show high rates of psychiatric disorders. However, little is known about the course of those disorders over time, or about mental health service use on the part of children and families during justice system involvement. Boys and girls recruited from their first contact with juvenile court (n=75), at a mean age of 13.6 years, completed three waves of interviews, each consisting of a structured clinical interview and questionnaires regarding service use, family functioning, parental burden, parental psychopathology. High rates of psychiatric disorders were evident. Three quarters (n = 56) met criteria for a mood, anxiety or behavioral disorder by parent or child report. Despite the high prevalence of mental health concerns, relatively few youth (approximately 20%) were involved in mental health services in follow-up waves. The presence of ODD and higher levels of family communication problems were associated with involvement in mental health services. Although parents experienced burden associated with their child's mental health problems, burden was not a strong correlate of help-seeking. Mental health problems declined from the point of initial involvement with juvenile justice; only ODD symptoms showed stability over time. Low rates of engagement in mental health services are found for juveniles subsequent to their first contact with juvenile justice. ODD and family communication problems most influenced service engagement, while burden due to mental health problems did not. The results provide potential targets for efforts to enhance parental motivation towards service engagement. PMID- 26557010 TI - Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology. AB - AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohn's disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1/Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of host-microbiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well known risk factor for CRC. Further insight may be translated into preventive and treatment strategies. PMID- 26557013 TI - Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis. AB - NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis. PMID- 26557014 TI - Effects of Free Anthraquinones Extract from the Rhubarb on Cell Proliferation and Accumulation of Extracellular Matrix in High Glucose Cultured-Mesangial Cells. AB - Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of currently available strategies for the prevention of DN remains unsatisfactory. In this study, we investigated the effects of free anthraquinones (FARs) extract, which was extracted from the rhubarb and purified by macroporous resin DM130 with gradient mixtures of ethanol/water as the lelution solvents, in high glucose-cultured glomerular mesangial cells (MCs). The cell proliferation was determined by CCK-8 assay, the levels of TGF-beta1, CTGF, ColIV and FN proteins in the supernatant of MCs were measured by ELISA assays, and the mRNA levels of these four genes were detected by RT-PCR. The results showed that the increased proliferation of MCs, the mRNA levels and protein expression of TGF-beta1, CTGF, ColIV and FN induced by high glucose were inhibited after the treatment with the FARs extract. This indicated that FARs extract could inhibit cell proliferation and the expression of main extracellular matrix induced by high glucose in MCs. The FARs extract exhibited potential values for prophylaxis and therapy of DN. PMID- 26557015 TI - Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress. AB - Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL 1beta and TNF-alpha mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress. PMID- 26557016 TI - Pitavastatin Regulates Ang II Induced Proliferation and Migration via IGFBP-5 in VSMC. AB - Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension. PMID- 26557017 TI - Nitric Oxide-Induced Autophagy in MC3T3-E1 Cells is Associated with Cytoprotection via AMPK Activation. AB - Nitric oxide (NO) is important in the regulation of bone remodeling, whereas high concentration of NO promotes cell death of osteoblast. However, it is not clear yet whether NO-induced autophagy is implicated in cell death or survival of osteoblast. The present study is aimed to examine the role of NO-induced autophagy in the MC3T3-E1 cells and their underlying molecular mechanism. The effect of sodium nitroprusside (SNP), an NO donor, on the cytotoxicity of the MC3T3-E1 cells was determined by MTT assay and expression of apoptosis or autophagy associated molecules was evaluated by western blot analysis. The morphological observation of autophagy and apoptosis by acridine orange stain and TUNEL assay were performed, respectively. Treatment of SNP decreased the cell viability of the MC3T3-E1 cells in dose- and time-dependent manner. SNP increased expression levels of p62, ATG7, Beclin-1 and LC3-II, as typical autophagic markers and augmented acidic autophagolysosomal vacuoles, detected by acridine orange staining. However, pretreatment with 3-methyladenine (3MA), the specific inhibitor for autophagy, decreased cell viability, whereas increased the cleavage of PARP and caspase-3 in the SNP-treated MC3T3-E1 cells. AMP-activated protein kinase (AMPK), a major autophagy regulatory kinase, was activated in SNP-treated MC3T3-E1 cells. In addition, pretreatment with compound C, an inhibitor of AMPK, decreased cell viability, whereas increased the number of apoptotic cells, cleaved PARP and caspase-3 levels compared to those of SNP-treated MC3T3-E1 cells. Taken together, it is speculated that NO-induced autophagy functions as a survival mechanism via AMPK activation against apoptosis in the MC3T3-E1 cells. PMID- 26557018 TI - Mind Bomb-2 Regulates Hippocampus-dependent Memory Formation and Synaptic Plasticity. AB - Notch signaling is a key regulator of neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-2 (Mib2) is an essential positive regulator of the Notch pathway, which acts in the Notch signal-sending cells. Therefore, genetic deletion of Mib2 in the mouse brain might help understand Notch signaling-mediated cell-cell interactions between neurons and their physiological function. Here we show that deletion of Mib2 in the mouse brain results in impaired hippocampal spatial memory and contextual fear memory. Accordingly, we found impaired hippocampal synaptic plasticity in Mib2 knock-out (KO) mice; however, basal synaptic transmission did not change at the Schaffer collateral-CA1 synapses. Using western blot analysis, we found that the level of cleaved Notch1 was lower in Mib2 KO mice than in wild type (WT) littermates after mild foot shock. Taken together, these data suggest that Mib2 plays a critical role in synaptic plasticity and spatial memory through the Notch signaling pathway. PMID- 26557019 TI - Enhancement of GluN2B Subunit-Containing NMDA Receptor Underlies Serotonergic Regulation of Long-Term Potentiation after Critical Period in the Rat Visual Cortex. AB - Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, gamma aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network. PMID- 26557020 TI - Electrophysiological and Mechanical Characteristics in Human Ileal Motility: Recordings of Slow Waves Conductions and Contractions, In vitro. AB - Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity. Slow waves were detected with a frequency of 9~10/min. There were no cross-sectional differences in resting membrane potential (RMP), amplitude or frequency between outer and inner circular muscle (CM), suggesting that electrical activities could be effectively transmitted from outer to inner CM. The presence of the interstitial cell of Cajal (ICC) at the linia septa was verified by immunohistochemistry. Contractions of strips and segments occurred at a frequency of 3~4/min and 1~2/min, respectively. The frequency, amplitude and area under the curve were similar between CM and LM. In segments, contractions of CM were associated with LM, but propagation varied with antegrade and retrograde directions. Atropine, N(W)-oxide-L-arginine, and sodium nitroprusside exhibited different effects on RMP and contractions. There were no cross-sectional differences with regard to the characteristics of slow waves in CM. The frequency of contractions in smooth muscle strips and ileal segments was lower than slow waves. The directions of propagation were diverse, indicating both mixing and transport functions of the ileum. PMID- 26557021 TI - Combined Skin Moisturization of Liposomal Serine Incorporated in Hydrogels Prepared with Carbopol ETD 2020, Rhesperse RM 100 and Hyaluronic Acid. AB - We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water in-oil (W/O) cream); their moisturizing abilities were then assessed using a Corneometer(r). The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products. PMID- 26557022 TI - Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells. AB - We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors/PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype. PMID- 26557023 TI - Is there a Hispanic Health Paradox in Sensitivity to Air Pollution? Hospital Admissions for Asthma, Chronic Obstructive Pulmonary Disease and Congestive Heart Failure Associated with NO2 and PM2.5 in El Paso, TX, 2005-2010. AB - STUDY OBJECTIVE: Linkages between pollution and morbidity have been observed in numerous studies. But race/ethnicity has been underemphasized as a modifier of that association, and few studies have tested for a Hispanic Health Paradox in sensitivity to air pollution. METHODS: Daily asthma, chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) hospital admissions in El Paso, Texas were studied in age groups and insurance groups. Daily PM2.5 and NO2 were calculated from pollution monitors and all models adjusted for apparent temperature and wind speed. Conditional logistic regression for the case crossover design was used for a between-group comparison and for a within-group comparison for Hispanics. RESULTS: Hispanics were at lower risk than non-Hispanic whites and non-Hispanics of other races for NO2-associated admissions, but at greater risk for PM2.5-associated admissions. While Hispanics were generally protected with regards to NO2, Hispanic children (vs. elderly) faced increased risk for asthma and uninsured Hispanics (vs. Private) faced increased risk for COPD admissions. While Hispanics were at increased risk of PM2.5-associated admissions, certain characteristics heightened their risks: being a Hispanic child (vs. Elderly) for asthma; being a Hispanic with Medicare (vs. Private) for asthma; and being a Hispanic with private insurance (vs. all other insurance types) for CHF. The main effect of pollution on admissions was more significant for asthma and CHF than for COPD, which had the fewest cases. CONCLUSIONS: There was heterogeneity in sensitivity to air pollution based on social characteristics and moderate evidence for a Hispanic Health Paradox in sensitivity to NO2. PMID- 26557024 TI - Influence of nematode Anguillicoloides crassus infestation on the cellular and humoral innate immunity in European eel (Anguilla anguilla L.). AB - Parasitic invasions are recognized as one of the primary factors responsible for decreasing populations of European eel. The aim of the present study was to determine the influence of infestation with the nematode Anguillicoloides crassus on the innate immunity in European eel (Anguilla anguilla). Anguillicoloides crassus parasitizes the swim bladder of this fish. Levels of the following immunological parameters were measured: spleen phagocyte respiratory burst activity, spleen phagocyte potential killing activity, pronephros lymphocyte proliferation stimulated by concanavaline A or lipopolisaccharide, plasma lysozyme and ceruloplasmin activity, total protein and immunoglobulin (Ig) serum levels. The analyses of the results of humoral and cellular immunity indicate that all studied parameters were statistically significant higher (p < 0.05) in non-infested fish compared to the ones with anguillicolosis except for ceruloplasmin level. These data suggest that the A. crassus infestation in European eel is responsible for a decreased immune response what could result in higher susceptibility to other pathogenic conditions. PMID- 26557025 TI - Spatio-temporal expression of blunt snout bream (Megalobrama amblycephala) mIgD and its immune response to Aeromonas hydrophila. AB - The function of IgD in fish and mammals has not been fully understood since its discovery. In this study, we have isolated and characterized the cDNA that encodes membrane-bound form of the immunoglobulin D heavy chain gene (mIgD) of blunt snout bream (Megalobrama amblycephala) using RT-PCR and rapid amplification of cDNA ends (RACE). The full-length cDNA of mIgD consisted of 3313 bp, encoding a putative protein of 943 amino acids. The structure of blunt snout bream mIgD is VDJ-MU1-delta1-delta2-delta3-delta4-delta5-delta6-delta7-TM. Multiple alignment and phylogenetic analyses indicated that blunt snout bream mIgD clusters with the homologues of cyprinid fish and that its highest identity is with that of C. idella (82%). The mIgD expression in early different developmental stages showed that the level of mIgD mRNA decreased dramatically from the unfertilized egg stage to the 32-cell stage, suggesting that mIgD mRNA was maternally transferred. As cell differentiation initially took place in the blastula stage, the mIgD expression increased significantly from the blastula stage to prelarva, which might be attributed to embryonic stem cell differentiation processes. Compared with juvenile fish, the expression and tissue distribution patterns of mIgD in adult individuals exhibited considerable variation. After the injection of Aeromonas hydrophila, mIgD expression was up-regulated in various tissues, reaching the peak expression at 5 d, 14 d or 21 d (depending on the tissue type). The present study provides a theoretical basis for further research of the teleost immune system. PMID- 26557026 TI - Blockade of B-cell activating factor with TACI-IgG effectively reduced Th1 and Th17 cells but not memory T cells in experimental allergic encephalomyelitis mice. AB - B-cell activating factor (BAFF) is regarded as a new therapeutic target in autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Along with other researchers, we have demonstrated that BAFF inhibitor atacicept (TACI-IgG) suppresses lupus and experimental allergic encephalomyelitis (EAE) by reducing the mature B-cell number but not memory B cells. It is however unclear whether TACI-Ig affects pathogenic T cells and memory T cells. In the present study, we found that blocking BAFF with TACI-IgG effectively reduces the pathogenic Th1 and Th17 cells in EAE mice. However, TACI IgG did not reduce memory CD62L(+)CD44(hi)CD4(+) and CD62L(+)CD44(hi)CD8(+) T cells in EAE mice. When interleukin (IL)-15 was neutralized, memory CD62L(+)CD44(hi) T cells were significantly reduced in TACI-IgG-treated EAE mice. These results suggest that TACI-IgG is effective in effective controlling Th1 and Th17 cells, but it also increases IL-15 to upregulate memory T cells in EAE mice. The study provides hints for the clinical application of the combination of BAFF- and IL-15-specific therapeutic agents. PMID- 26557027 TI - Immune function of Chinese formula Qingwen Baidu granule in broilers. AB - This study was to investigate the effects of Qingwen Baidu granules on the antibody level, immune organ index and the lymphocyte transformation of broilers. Hy-line variety white cocks of 30 days were used to evaluate the antibody titer of Newcastle Disease in each serum group, and MTT method was used to determine the T lymphocyte proliferation, and organ weighing methods to measure the immune organ index 21 days after immunization. The results showed that Qingwen Baidu granules could prolong the residue time in the body, improve the lymphocyte conversion ratio, increase the bursa, thymus and spleen index and promote immune organ development. These results suggested that Qingwen Baidu granules could improve the serum Newcastle disease antibody level, improve peripheral blood lymphocyte proliferation, enhance the cellular immune function, and elevate the immune organ index and growth, in order to raise the immune function in chicken. The above demonstrates that the Qingwen Baidu granules have significant effects on the cytoimmunity and humoral immunity, and the potentiation of the immune function in broilers. PMID- 26557028 TI - Association between interleukin 8 receptor alpha gene (CXCR1) and mastitis in dairy cattle. AB - The innate immune response plays an important role in the course of bacterial infections. Innate immunity effectiveness relies on the expression of many genes, connected, among others, to the activity of neutrophils. Interleukin 8 (IL-8) receptor alpha, coded by the CXCR1 gene, is present on the neutrophil surface and binds pro-inflammatory IL-8 with high affinity. This is why the bovine CXCR1 gene carries a potential for use as a dairy cattle mastitis marker. To date, several studies on the CXCR1 polymorphism brought out contradictory results. The aim of this study was to analyse the association between two SNPs of the CXCR1 gene, which is potentially important for the protein function and animal phenotype for mastitis susceptibility. A total of 554 Polish Holsteins were genotyped, and 140 among them were bacteriologically tested. The differences between animals carrying different genotypes and haplotypes of CXCR1 in test day somatic cell count (SCC) and Staphylococcus aureus mastitis susceptibility were estimated. We found that test day SCC was significantly related to CXCR1+472 SNP but not to CXCR1+735 SNP. No statistically significant association between CXCR1 polymorphism and susceptibility to S. aureus mastitis was found in the studied herd. PMID- 26557029 TI - The cardioprotective potential of valsartan in myocardial ischaemia reperfusion injury. AB - BACKGROUND: Ischaemia/reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischaemia with inadequate oxygen followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may aggravate local injury as well as induce impairment of remote organ function by mechanisms that involve oxidative stress, inflammation, and apoptosis. OBJECTIVE: This study was undertaken to investigate the potential role of valsartan angiotensin receptor blocker-1 (ARB-1) in the amelioration of myocardial ischaemia/reperfusion injury induced by ligation of coronary artery in a rat model. MATERIAL AND METHODS: Adult male Albino rats were randomised into four equal groups (seven rats in each group). In group 1 (sham group) the rats underwent the same anaesthetic and surgical procedure as the control group except for ligation of the left anterior descending (LAD) coronary artery; group 2 (control group) rats were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for 2 hours; group 3 (control vehicle group) rats received (normal saline) vehicle of valsartan via IP injection and were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for two hours; group 4 (valsartan treated group) rats were pretreated with valsartan 10 mg/kg IP 30 minutes before ligation of LAD coronary artery. At the end of the experiment, blood samples were taken by direct cardiac puncture for the measurement of plasma levels of troponin T (cTnT) and serum levels for both malondialdehyde MDA and glutathione GSH. After blood sampling, the heart was removed and divided into two parts; the apex was used for histopathological examination, and the remaining part was used for the measurement of cardiac tissue levels of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 10 (IL-10), cysteine aspartic acid-protease 3 (caspase-3), and BCL2-associated X protein (BAX), after removal of the remaining blood clots and aorta. RESULTS: In the active control group, as compared with the sham group, the results revealed that the myocardial tissue levels of inflammatory cytokines TNF-alpha, IL-6, IL-10, caspase-3, and BAX, and the plasma level of cTnT and serum level of malondialdehyde MDA were significantly increased (p < 0.001), while the serum level of glutathione GSH was significantly decreased (p < 0.001). Regarding the histopathological part of the study, all rats in the active control group showed a significant cardiac tissue injury (p < 0.001) compared with the sham group. Valsartan significantly counteracted (p < 0.001) the increase in the myocardial tissue levels of TNF-alpha, IL-6, caspase-3, and BAX; additionally, it counteracted the increase in plasma level of cTnT and serum level of malondialdehyde MDA, while valsartan produced highly significant elevation (p < 0.001) in the cardiac tissue level of IL-10 and serum level of glutathione GSH and significantly reduced (p < 0.001) the cardiac tissue injury in the valsartan pretreated rats. CONCLUSIONS: The results of the present study reveal that valsartan ameliorates myocardial ischaemia reperfusion injury in rats by interfering with inflammatory reactions and apoptosis that are induced by ischaemia reperfusion injury. PMID- 26557030 TI - Recurrent respiratory tract infections in children - analysis of immunological examinations. AB - BACKGROUND: Paediatric respiratory tract infections are among the most common reasons for preschool and school absences and visits to physicians. The disease mainly involves the upper respiratory tract and is associated with fever, cough, sore throat, and running nose. Children with recurrent respiratory infections (RRI), which are defined as more than six serious diseases a year, are a difficult diagnostic challenge. The aim of this study was to assess immunological deviations in laboratory tests performed in children with RRI. MATERIAL AND METHODS: In the retrospective study 25 children suffering from recurrent respiratory tract infection, aged 4.1 +/-2.3 years, 13 boys and 12 girls, were involved. For all children chemiluminescence of granulocytes and immunophenotyping of lymphocytes from peripheral blood were examined. An immunophenotype of peripheral blood lymphocytes involved evaluation of T cell, B cells, and NK cells, examined with flow cytometry. RESULTS: Eleven of the studied children had decreased chemiluminescent response to stimulants, normal response was found for nine children, and five children had an increased result of the test. Five of the 25 children had decreased B cells number, and five had decreased number of T cells including decrease of CD4, as well as CD8 positive cells. Children with decreased chemiluminescence had more frequent neutropaenia than children with normal or increased chemiluminescent response, p < 0.05 (exact Fisher test). CONCLUSIONS: Recurrent respiratory tract infection could be associated with improper neutrophils response to pathogens, and immunological examination should be performed to find the reason for the increased number of infections in a year. PMID- 26557031 TI - Problem of immunoglobulin M co-detection in serological response to bacterial and viral respiratory pathogens among children suspected of legionellosis. AB - The objective of this research was an analysis of the serological response to respiratory bacterial and viral pathogens, in 156 children admitted to hospital in Warsaw with a suspicion of legionellosis. Levels of immunoglobulin (Ig) M to Bordetella pertussis, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), adenoviruses, human parainfluenza virus (HPIV) t. 1-4 and influenza t. A + B viruses were determined retrospectively by ELISAs. In the prospective examinations (only Legionella pneumophila sg1), a positive level of IgM was found in 35 patients, but in 59 children together with retrospective tests. There were positive results for B. pertussis (21 children), followed by HPIV (10 children), M. pneumoniae (5 patients), RSV (4 persons), adenoviruses (3 children), and influenza A + B virus (3 persons). Positive results for > 1 agent were found in 16 children. The most often co-detected IgM were to L. pneumophila sg1 and B. pertussis (9 children) and L. pneumophila sg1 and M. pneumoniae (5 patients). The distribution of IgM to L. pneumophila sg1, B. pertussis and HPIV among children <= 4 years differed significantly from IgM specific to other pathogens. A high number of HPIV infections, mainly single, was found among infants. Positive results of IgM to L. pneumophila sg1 were mainly found in children aged 4-5 years. and the oldest children (over 10 years.). However, among the oldest children, anti-L. pneumophila sg1 antibodies were often found together with IgM to B. pertussis. Infections due to more than 2 pathogens were only observed among patients with pneumonia, especially due to L. pneumophila sg1 and/or B. pertussis. Conversely, co-detection of IgM ELISA for L. pneumophila and M. pneumoniae were mainly detected among patients hospitalized without pneumonia. PMID- 26557032 TI - Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis? AB - The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires' disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children <4 yrs.old, the reduction of anti-B. pertussis IgM by both antigens was higher than for B. pertussis antigen alone. Based on the high difference (>= 2 times) between reduction by L.pneumophila sg1 and by B. pertussis antigen, legionellosis was confirmed in 8/19 children. The majority of them also indicated IgM positive/borderline results for B. pertussis or M.pneumoniae in routine ELISA tests. As a preliminary, we posed a hypothesis of a potential impact of an anti pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children. PMID- 26557033 TI - Efficacy of cytokine-induced killer cells in the treatment of elderly patients with metastatic pancreatic adenocarcinoma. AB - Currently, metastatic pancreatic cancer is associated with disappointing survival outcomes. This is largely due to a rapid progression of the disease and a precipitous deterioration in the health of affected individuals, especially elderly patients who are often unable to tolerate chemotherapy. The aim of this study was to evaluate the efficacy and safety of adoptive immunotherapy using cytokine-induced killer cells (CIK) as a first-line treatment for metastatic pancreatic cancer. Between December 2010 and June 2012 eight patients were enrolled in this study. All participants were elderly, suffering from metastatic pancreatic cancer, and unable to tolerate chemotherapy. All patients in this study received R-CIK therapy only as a first-line treatment. In the eight patients, 1 had complete response (CR), 5 had stable disease (SD) and 2 had progression disease (PD). Therefore, the overall response rate (ORR) was 12.5% (1/8) and the disease control rate (DCR) was 75.0% (6/8 patients). The 1-year survival rate was 37.5%, and the median overall survival time (mOS) was 13.04 months (95% CI: 5.9-20.2). The results indicated that no significant positive or negative predictive factors were identified by univariate analysis. The main adverse effect of R-CIK was fever and the side effect rate was 25.0% (2/8). Adoptive immunotherapy using R-CIK cells showed comparable OS to survival data seen in previous trials assessing conventional chemotherapies in elderly patients and the adverse effect is less pronounced. PMID- 26557034 TI - Archaea prevalence in inflamed pulp tissues. AB - Archaea have been detected in several ecological niches of the human body such as the large intestine, skin, vagina as well as the oral cavity. At present, archaea are recognized as nonpathogenic microorganisms. However, some data indicate that they may be involved in the etiopathogenesis of several diseases, including intestinal diseases as well as oral diseases: periodontitis, peri-implantitis and endodontitis. In this study, on the basis of 16S rRNA gene sequence analysis, we examined whether archaea might be present in inflamed pulp tissues and contribute to the development of endodontic infection. In comparison, we also determined selected bacterial species associated with endodontitis. We detected archaea in 85% of infected endodontic samples. In addition, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola were present in inflamed pulp tissue samples and Treponema denticola occurred with the highest frequency (70%). Further analysis revealed the presence of methanogenic archaea in analyzed samples. Direct sequencing of archaeal 16S rRNA gene PCR products indicated the occurrence of methanogenic archaea in inflamed pulp tissues; phylogenetically most similar were Methanobrevibacter oralis and Methanobrevibacter smithii. Therefore, our results show that methanogenic archaea are present in inflamed pulp tissues and may participate in the development of endodontic infection. PMID- 26557035 TI - Host response, obesity, and oral health. AB - Proper food choices are part of preventing or reducing the risk of dental caries and periodontal disease. A significant association has been proven between oral diseases and the incidence of systemic diseases. Obesity, just like smoking, is one of the major risk factors for oral disease and is a serious social problem that has reached epidemic proportions in many developed countries. The results of studies on periodontitis confirm the relationship between the values of body mass index (BMI) and the prevalence of periodontal diseases. Adipose tissue is an active endocrine organ and it performs many important functions in the body, such as thermal isolation and protection, storage, and secretion. Many cytokines are secreted proportionally to the amount of fat present and are actively involved in the metabolism of the whole system, including the functioning of the immune system. Therefore, obesity may alter the response of the host to the antigens derived from bacterial plaque, and thus cause disturbances in the inflammatory response in the course of periodontal disease. PMID- 26557036 TI - Current views on the mechanisms of immune responses to trauma and infection. AB - According to the World Health Organization, post-traumatic mortality rates are still very high and show an increasing tendency. Disorders of innate immune response that may increase the risk of serious complications play a key role in the immunological system response to trauma and infection. The mechanism of these disorders is multifactorial and is still poorly understood. The changing concepts of systemic inflammatory response syndrome (SIRS) and compensatory anti inflammatory response syndrome (CARS) early inflammatory response, presented in this work, have been extended to genetic studies. Overexpression of genes and increased production of immune response mediators are among the main causes of multiple organ dysfunction syndrome (MODS). Changes in gene expression detected early after injury precede the occurrence of subsequent complications with a typical clinical picture. Rapid depletion of energy resources leads to immunosuppression and persistent inflammation and immune suppression catabolism syndrome (PICS). Early diagnosis of immune disorders and appropriate nutritional therapy can significantly reduce the incidence of complications, length of hospital stay, and mortality. The study presents the development of knowledge and current views explaining the mechanisms of the immune response to trauma and infection. PMID- 26557037 TI - Neutrophil extracellular traps (Nets) impact upon autoimmune disorders. AB - Friend or foe? This is often asked question when it comes to neutrophil extracellular traps studies. There is no simple answer to that. At the time of their discovery they were considered to be protectors of our well-being. Excellent pathogen fighting skills were described as purely beneficial. But it was not long before those guardians of immunity reveal their dark side. What seemed to be profitable could also take its toll. They are perfectly constructed, made from nucleic deoxyribonucleic acid ornamented with cytoplasmic and granular proteins, to fight invaders. But this unique build is prone to become considered by our body as a threat. Since there is a thin line which when crossed turns a savior into enemy, it was postulated that Nets can play a significant role in autoimmune disorders pathogenesis and disease exacerbation. Recent years have brought a new insight into autoimmune disorders trying to connect the old knowledge and suspicions with modern discoveries. PMID- 26557039 TI - Selected aspects of the action of cobalt ions in the human body. AB - Cobalt is widespread in the natural environment and can be formed as an effect of anthropogenic activity. This element is used in numerous industrial applications and nuclear power plants. Cobalt is an essential trace element for the human body and can occur in organic and inorganic forms. The organic form is a necessary component of vitamin B12 and plays a very important role in forming amino acids and some proteins in nerve cells, and in creating neurotransmitters that are indispensable for correct functioning of the organism. Its excess or deficiency will influence it unfavourably. Salts of cobalt have been applied in medicine in the treatment of anaemia, as well as in sport as an attractive alternative to traditional blood doping. Inorganic forms of cobalt present in ion form, are toxic to the human body, and the longer they are stored in the body, the more changes they cause in cells. Cobalt gets into the body in several ways: firstly, with food; secondly by the respiratory system; thirdly, by the skin; and finally, as a component of biomaterials. Cobalt and its alloys are fundamental components in orthopaedic implants and have been used for about 40 years. The corrosion of metal is the main problem in the construction of implants. These released metal ions may cause type IV inflammatory and hypersensitivity reactions, and alternations in bone modelling that lead to aseptic loosening and implant failure. The ions of cobalt released from the surface of the implant are absorbed by present macrophages, which are involved in many of the processes associated with phagocytose orthopaedic biomaterials particles and release pro-inflammatory mediators such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-alpha), and prostaglandin. PMID- 26557038 TI - Cathelicidin impact on inflammatory cells. AB - Cathelicidins, like other antimicrobial peptides, exhibit direct antimicrobial activities against a broad spectrum of microbes, including both Gram-positive and Gram-negative bacteria, enveloped viruses, and fungi. These host-derived peptides kill the invaded pathogens by perturbing their cell membranes and can neutralize biological activities of endotoxin. Nowadays, more and more data indicate that these peptides, in addition to their antimicrobial properties, possess various immunomodulatory activities. Cathelicidins have the potential to influence and modulate, both directly and indirectly, the activity of various cell populations involved in inflammatory processes and in host defense against invading pathogens. They induce migration of neutrophils, monocytes/macrophages, eosinophils, and mast cells and prolong the lifespan of neutrophils. These peptides directly activate inflammatory cells to production and release of different pro-inflammatory and immunoregulatory mediators, cytokines, and chemokines, however cathelicidins might mediate the generation of anti inflammatory cytokines as well. Cathelicidins also modulate epithelial cell/keratinocyte responses to infecting pathogens. What is more, they affect activity of monocytes, dendritic cells, keratinocytes, or epithelial cells acting in synergy with cytokines or beta-defensins. In addition, these peptides indirectly balance TLR-mediated responses of monocytes, macrophages, dendritic cells, epithelial cells, and keratinocytes. This review discusses the role and significance of cathelicidins in inflammation and innate immunity against pathogens. PMID- 26557040 TI - The influence of the workplace-related biological agents on the immune systems of emergency medical personnel. AB - Emergency medical services workers' (EMSWs) acute exposures to many biological agents are frequent and well recognised in their workplaces, as well as occupational diseases resulting from some of these exposures. At the same time, there is only scant information on the adverse effects of chronic exposure to biological hazard factors on the immune systems of EMSWs. In the Polish legislation system, the Ordinance of the Minister of Health about harmful biological agents in the workplace and ways of protecting workers from exposure to those agents is an implement of Directive 2000/54/EC, which deals thoroughly with those issues in European Union Countries. Emergency medical services workers play an essential role as primary providers of pre-hospital emergency medical care, and they are part of the integral components of disaster response. Traumatic experiences can affect emergency medical staff immune systems negatively, by functioning as a chronic stressor. Conscious use of biological agents in workplaces such as microbial laboratories can be easily controlled and monitored. However, risk assessment is more difficult for workers when they are exposed unintentionally to biological agents. Exposure to bio-aerosols is considered especially harmful. This review summarises available information about biological risk factors for emergency medical services workers, and some information about the influence of these factors on their immune systems. PMID- 26557042 TI - Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. AB - B cell subsets have been found to exhibit a negative regulatory function, like Tregs. The present study investigates the effects of CD5+CD19+ interleukin (IL) 10 (B10) on the occurrence and development of oesophageal carcinoma by analysing B10 levels in the peripheral blood of patients with oesophageal carcinoma. Peripheral blood of 120 oesophageal cancer patients and 120 healthy controls were collected, and regulatory B cell counts were determined by flow cytometry. The level of B10 cells in the peripheral blood of patients with oesophageal carcinoma was significantly higher than that in healthy controls (p < 0.05). In addition, B10 levels in stage III-IV patients (3.5 +/-0.7%) were higher than those in stage I-II patients (2.5 +/-0.6%), which were in turn higher than those in the healthy controls (1.3 +/-0.3%). The level of B10 increased with clinical progression of oesophageal cancer, suggesting that B10 cells may influence the development or progression of oesophageal cancer. PMID- 26557043 TI - Asplenia in children with congenital heart disease as a cause of poor outcome. AB - The absence of a spleen is a well-known risk factor for severe bacterial infections, especially due to encapsulated bacteria. Congenital asplenia can be part of multiple congenital abnormalities as in heterotaxy including Ivemark syndrome with congenital anomalies of the heart or great vessels, or it can be isolated, which is extremely rare. In these cases, asplenia is an important factor effecting mortality. In this report, the clinical courses of five children with asplenia and concomitant minor or complex cardiac anomalies are presented. The ages of the children ranged between 1.5 and 17 months at the time of diagnosis. All of the cases had had a history of hospitalisation for infectious diseases before the diagnosis. The patient who was diagnosed at 17 months old had a history pneumonia, urinary tract infection, and bacterial meningitis beginning at five months old. Three children had complex cardiac anomalies, one child had ventricular septal defect, and one child had atrial septal defect. Howell-Jolly bodies were determined in peripheral blood smear in all of the patients. The diagnoses of asplenia were confirmed with spleen scintigraphy. One of the patients with complex cardiac anomalies died a short time after diagnosis, because of cardiac failure. The rest of the four patients were vaccinated for encapsulated bacteria and were taken under antibiotic prophylaxis. These children did not need hospitalisation for infectious diseases during the follow-up period (5-40 months). In asplenic children, early diagnosis, antibiotic prophylaxis, and immunisation for encapsulated bacteria can decrease the risk of morbidity and mortality. PMID- 26557041 TI - Angiomodulatory properties of Rhodiola spp. and other natural antioxidants. AB - Disturbances of angiogenesis and oxidative stress can lead to many serious diseases such as cancer, diabetes or ischemic heart disease. Substances neutralizing oxidative stress are known as antioxidants. They can affect angiogenesis process also, and thus, they modulate therapy results. Antioxidants become more and more frequently used in order to maintain homeostasis of the organism and diminish the risk of disease. Herein, we introduce some antioxidant preparations of natural plant origin (Rhodiola, Aloe vera, Resveratrol, Echinacea, Plumbagin) and antioxidant supplements (Padma 28, Reumaherb, Resvega). Analyses of their angiogenic properties, their multidirectional molecular effect on angiogenesis as well as medical application are within the scope of this review. Most of presented preparations down regulate neovascularization. They can be safely administered to patients with abnormally high angiogenesis. Rhodiola modulates, and Echinacea, Aloe vera and Plumbagin inhibit tumour-related angiogenesis in vitro and in vivo (animal models). Resveratrol and Resvega reduce neovascularization in the eye and may be applicable in eye disorders. Padma 28 preparation exhibits angioregulatory activity, decreasing high angiogenesis of cancer cells and increasing physiological angiogenesis, therefore can be used in therapy of patients with various disturbances of angiogenesis. Antioxidant application in the case of angiogenesis-related diseases should take into consideration angiogenic status of the patient. PMID- 26557044 TI - Differences in alcohol brand consumption among underage youth by age, gender, and race/ethnicity - United States, 2012. AB - AIM: No previous national study has reported the prevalence of alcohol brand consumption among underage youth by demographic characteristics. The aim of this study was to determine the alcohol brand preferences among underage drinkers in different demographic categories. METHOD: We administered an online survey to a national sample of 1,031 underage youth, ages 13-20, who had consumed at least one drink of alcohol in the past 30 days. The sample was recruited from a previously established internet survey panel. The main outcome measure was the estimated 30-day consumption prevalence for each of 898 brands by age, gender, and race/ethnicity. RESULTS: Two beer brands-Bud Light and Budweiser-are uniformly popular among underage drinkers, regardless of age, gender, or race/ethnicity. There are several hard liquor brands whose use increases markedly with age. Two flavored alcoholic beverages sharing the names of hard liquor brands-Smirnoff and Bacardi-are more popular with older youth. Some flavored alcoholic beverages are about twice as popular among female underage drinkers. There are 12 alcohol brands that are uniquely popular among Black underage drinkers, and these brands are heavily promoted in urban music. CONCLUSION: There are differential patterns of brand-specific alcohol use among underage drinkers. PMID- 26557045 TI - Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study. AB - BACKGROUND: In the few studies available, the risk of developing systemic reactions (SR) to hymenoptera stings in patients with previous large local reactions (LLRs) to stings ranges from 0 to 7 %. We evaluated both retrospectively and prospectively the risk of SRs in patients with LLRs to stings. METHODS: An overall number of 477 patients, 396 with an SR as the first manifestation of allergy and 81 with a history of only LLRs after hymenoptera stings, were included in the study. All patients had clinical history and allergy testing (skin tests and/or specific IgE) indicative of allergy to venom of only one kind of Hymenoptera. Of the 81 patient with LLRs, 53 were followed-up for 3 years by annual control visits, while the 396 patients with SR were evaluated retrospectively. RESULTS: Among the 396 patients with an SR, only 17 (4.2 %) had had a previous LLR as debut of allergy, after an history of normal local reactions to Hymenoptera stings. All the 81 patients with a history of only LLRs had previously had at least two LLRs, with an overall number of 238 stings and no SR. Among the 53 patients who were prospectively evaluated we found that 31 of them (58.3 %) were restung by the same type of insect, with an overall number of 59 stings, presenting only LLRs and no SR. CONCLUSIONS: Our findings confirm that patients with repeated LLRs to stings had no risk of SR, while a single LLR does not exclude such risk. This has to be considered in the management of patients with LLRs. PMID- 26557046 TI - MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations. AB - Clinically amyopathic dermatomyositis (CADM), described almost 50 years ago, is defined on the basis of still not validated criteria and characterized by skin findings almost without muscle weakness. Autoantibodies directed against the cytosolic pathogen sensor MDA5 (CADM 140) can mark this subtype of dermatomyositis which has been reported to associate, in particular ethnic groups, with severe progressive interstitial lung disease, poor prognosis and an hyperferritinemic status resembling hemophagocytic-like syndromes. MDA5 may be relevant in that Interferon-signature claimed to characterize inflammatory myopathies and dermatomyosits itself, but its role is not clear. However, the titre of anti-MDA5 autoantibodies seems to correlate with the outcome. In Caucasian populations the association between anti-MDA5 positive CADM and rapidly progressive interstitial lung disease seems to be weaker, but the limited numbers of patients described so far could explain the lack of statistical significance. As a fact, European patients with circulating anti-MDA5 autoantibodies may be clinically inhomogeneous and exhibit different rates of severity. The two patients affected by anti-MDA5 positive dermatomyositis described hereafter provide a clear example of the extreme variability of the disease in terms of laboratory findings and clinical features. PMID- 26557047 TI - Head Motion Modeling for Human Behavior Analysis in Dyadic Interaction. AB - This paper presents a computational study of head motion in human interaction, notably of its role in conveying interlocutors' behavioral characteristics. Head motion is physically complex and carries rich information; current modeling approaches based on visual signals, however, are still limited in their ability to adequately capture these important properties. Guided by the methodology of kinesics, we propose a data driven approach to identify typical head motion patterns. The approach follows the steps of first segmenting motion events, then parametrically representing the motion by linear predictive features, and finally generalizing the motion types using Gaussian mixture models. The proposed approach is experimentally validated using video recordings of communication sessions from real couples involved in a couples therapy study. In particular we use the head motion model to classify binarized expert judgments of the interactants' specific behavioral characteristics where entrainment in head motion is hypothesized to play a role: Acceptance, Blame, Positive, and Negative behavior. We achieve accuracies in the range of 60% to 70% for the various experimental settings and conditions. In addition, we describe a measure of motion similarity between the interaction partners based on the proposed model. We show that the relative change of head motion similarity during the interaction significantly correlates with the expert judgments of the interactants' behavioral characteristics. These findings demonstrate the effectiveness of the proposed head motion model, and underscore the promise of analyzing human behavioral characteristics through signal processing methods. PMID- 26557048 TI - Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat. AB - The potential for exposures to ionizing radiation has increased in recent years. Although advances have been made, understanding the global metabolic response as a function of both dose and exposure time is challenging considering the complexity of the responses. Herein we report our findings on the dose- and time dependency of the urinary response to ionizing radiation in the male rat using radiation metabolomics. Urine samples were collected from adult male rats, exposed to 0.5 to 10 Gy gamma-radiation, both before from 6 to 72 h following exposures. Samples were analyzed by liquid chromatography coupled with time-of flight mass spectrometry, and deconvoluted mass chromatographic data were initially analyzed by principal component analysis. However, the breadth and complexity of the data necessitated the development of a novel approach to summarizing biofluid constituents after exposure, called Visual Analysis of Metabolomics Package (VAMP). VAMP revealed clear urine metabolite profile differences to as little as 0.5 Gy after 6 h exposure. Via VAMP, it was discovered that the response to radiation exposure found in rat urine is characterized by an overall net down-regulation of ion excretion with only a modest number of ions excreted in excess over pre-exposure levels. Our results show both similarities and differences with the published mouse urine response and a dose- and time-dependent net decrease in urine ion excretion associated with radiation exposure. These findings mark an important step in the development of minimally invasive radiation biodosimetry. VAMP should have general applicability in metabolomics to visualize overall differences and trends in many sample sets. PMID- 26557050 TI - Noncoding RNA in the transcriptional landscape of human neural progenitor cell differentiation. AB - Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8 and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer's disease. Weighted gene co-expression network analysis (WGCNA) was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7 to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders. PMID- 26557049 TI - Current insights into the molecular mechanisms of hypoxic pre- and postconditioning using hypobaric hypoxia. AB - Exposure of organisms to repetitive mild hypoxia results in development of brain hypoxic/ischemic tolerance and cross-tolerance to injurious factors of a psycho emotional nature. Such preconditioning by mild hypobaric hypoxia functions as a "warning" signal which prepares an organism, and in particular the brain, to subsequent more harmful conditions. The endogenous defense processes which are mobilized by hypoxic preconditioning and result in development of brain tolerance are based on evolutionarily acquired gene-determined mechanisms of adaptation and neuroprotection. They involve an activation of intracellular cascades including kinases, transcription factors and changes in expression of multiple regulatory proteins in susceptible areas of the brain. On the other hand they lead to multilevel modifications of the hypothalamic-pituitary-adrenal endocrine axis regulating various functions in the organism. All these components are engaged sequentially in the initiation, induction and expression of hypoxia-induced tolerance. A special role belongs to the epigenetic regulation of gene expression, in particular of histone acetylation leading to changes in chromatin structure which ensure access of pro-adaptive transcription factors activated by preconditioning to the promoters of target genes. Mechanisms of another, relatively novel, neuroprotective phenomenon termed hypoxic postconditioning (an application of mild hypoxic episodes after severe insults) are still largely unknown but according to recent data they involve apoptosis-related proteins, hypoxia-inducible factor and neurotrophins. The fundamental data accumulated to date and discussed in this review open new avenues for elaboration of the effective therapeutic applications of hypoxic pre- and postconditioning. PMID- 26557051 TI - Circuits regulating pleasure and happiness: the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates. AB - The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory, and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and relate to more sophisticated behavioral manifestations such as mood. An animal comparable to lampreys was the earliest known vertebrate with a modern forebrain consisting of old and new cortical parts. Lampreys have a separate dorsal pallium, the forerunner of the most recently developed part of the cerebral cortex. In addition, the lamprey extrapyramidal system (EPS), which regulates movement, is modern. However, in lampreys and their putative forerunners, the hagfishes, the striatum, which is the input part of this EPS, probably corresponds to the human centromedial amygdala, which in higher vertebrates is part of a system mediating fear and anxiety. Both animals have well-developed nuclear habenulae, which are involved in several critical behaviors; in lampreys this system regulates the reward system that reinforces appetitive-seeking behavior or the avoidance system that reinforces flight behavior resulting from negative inputs. Lampreys also have a distinct glutamatergic nucleus, the so-called habenula-projection globus pallidus, which receives input from glutamatergic and GABAergic signals and gives output to the lateral habenula. Via this route, this nucleus influences midbrain monoaminergic nuclei and regulates the food acquisition system. These various structures involved in motor regulation in the lampreys may be conserved in humans and include two complementary mechanisms for reward reinforcement and avoidance behaviors. The first system is associated with experiencing pleasure and the second with happiness. The activities of these mechanisms are regulated by a tract running via the habenula to the upper brainstem. Identifying the human correlate of the lamprey habenula-projecting globus pallidus may help in elucidating the mechanism of the antidepressant effects of glutamatergic drugs. PMID- 26557052 TI - Assessing intracortical myelin in the living human brain using myelinated cortical thickness. AB - Alterations in the myelination of the cerebral cortex may underlie abnormal cortical function in a variety of brain diseases. Here, we describe a technique for investigating changes in intracortical myelin in clinical populations on the basis of cortical thickness measurements with magnetic resonance imaging (MRI) at 3 Tesla. For this, we separately compute the thickness of the shallower, lightly myelinated portion of the cortex and its deeper, heavily myelinated portion (referred to herein as unmyelinated and myelinated cortex, respectively). Our expectation is that the thickness of the myelinated cortex will be a specific biomarker for disruptions in myeloarchitecture. We show representative atlases of total cortical thickness, T, unmyelinated cortical thickness, G, and myelinated cortical thickness, M, for a healthy group of 20 female subjects. We further demonstrate myelinated cortical thickness measurements in a preliminary clinical study of 10 bipolar disorder type-I subjects and 10 healthy controls, and report significant decreases in the middle frontal gyrus in T, G, and M in the disorder, with the largest percentage change occurring in M. This study highlights the potential of myelinated cortical thickness measurements for investigating intracortical myelin involvement in brain disease at clinically relevant field strengths and resolutions. PMID- 26557053 TI - A retrograde adeno-associated virus for collecting ribosome-bound mRNA from anatomically defined projection neurons. AB - The brain contains a large variety of projection neurons with different functional properties. The functional properties of projection neurons arise from their connectivity with other neurons and their molecular composition. We describe a novel tool for obtaining the gene expression profiles of projection neurons that are anatomically defined by the location of their soma and axon terminals. Our tool utilizes adeno-associated virus serotype 9 (AAV9), which we found to retrogradely transduce projection neurons after injection at the site of the axon terminals. We used AAV9 to express Enhanced Green Fluorescent Protein (EGFP)-tagged ribosomal protein L10a (EGFP-L10a), which enables the immunoprecipitation of EGFP-tagged ribosomes and associated mRNA with a method known as Translating Ribosome Affinity Purification (TRAP). To achieve high expression of the EGFP-L10a protein in projection neurons, we placed its expression under control of a 1.3 kb alpha-calcium/calmodulin-dependent protein kinase II (Camk2a) promoter. We injected the AAV9-Camk2a-TRAP virus in either the hippocampus or the bed nucleus of the stria terminalis (BNST) of the mouse brain. In both brain regions the 1.3 kb Camk2a promoter did not confer complete cell type specificity around the site of injection, as EGFP-L10a expression was observed in Camk2a-expressing neurons as well as in neuronal and non-neuronal cells that did not express Camk2a. In contrast, cell-type specific expression was observed in Camk2a-positive projection neurons that were retrogradely transduced by AAV9-Camk2a-TRAP. Injection of AAV9-Camk2a-TRAP into the BNST enabled the use of TRAP to collect ribosome-bound mRNA from basal amygdala projection neurons that innervate the BNST. AAV9-Camk2a-TRAP provides a single-virus system that can be used for the molecular profiling of anatomically defined projection neurons in mice and other mammalian model organisms. In addition, AAV9-Camk2a-TRAP may enable the discovery of protein synthesis events that support information storage in projection neurons. PMID- 26557054 TI - Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y 27632 in a pilocarpine model of temporal lobe epilepsy. AB - Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20-30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down regulation and pathological distribution of the K(+)-Cl(-) cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE. PMID- 26557055 TI - Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus. AB - Chronic tinnitus is associated with neuroplastic changes in auditory and non auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63 channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6 fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity. PMID- 26557056 TI - TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary alpha2delta4 subunit. AB - Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary alpha2delta4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant alpha2delta4 subunit. Collectively, our experiments show association between TMEM16A and the alpha1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID- 26557057 TI - Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS? AB - Stress granules (SGs) are RNA-containing cytoplasmic foci formed in response to stress exposure. Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications). Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation. SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression. Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS. We propose that TDP-43 and FUS serve as an interface between genetic susceptibility and environmental stress exposure in disease pathogenesis. Here, we will discuss the role of TDP-43 and FUS in SG dynamics and how disease-linked mutations affect this process. PMID- 26557059 TI - Looming sensitive cortical regions without V1 input: evidence from a patient with bilateral cortical blindness. AB - Fast and automatic behavioral responses are required to avoid collision with an approaching stimulus. Accordingly, looming stimuli have been found to be highly salient and efficient attractors of attention due to the implication of potential collision and potential threat. Here, we address the question of whether looming motion is processed in the absence of any functional primary visual cortex and consequently without awareness. For this, we investigated a patient (TN) suffering from complete, bilateral damage to his primary visual cortex. Using an fMRI paradigm, we measured TN's brain activation during the presentation of looming, receding, rotating, and static point lights, of which he was unaware. When contrasted with other conditions, looming was found to produce bilateral activation of the middle temporal areas, as well as the superior temporal sulcus and inferior parietal lobe (IPL). The latter are generally thought to be involved in multisensory processing of motion in extrapersonal space, as well as attentional capture and saliency. No activity was found close to the lesioned V1 area. This demonstrates that looming motion is processed in the absence of awareness through direct subcortical projections to areas involved in multisensory processing of motion and saliency that bypass V1. PMID- 26557058 TI - Quantification of mid and late evoked sinks in laminar current source density profiles of columns in the primary auditory cortex. AB - Current source density (CSD) analysis assesses spatiotemporal synaptic activations at somatic and/or dendritic levels in the form of depolarizing current sinks. Whereas many studies have focused on the short (<50 ms) latency sinks, associated with thalamocortical projections, sinks with longer latencies have received less attention. Here, we analyzed laminar CSD patterns for the first 600 ms after stimulus onset in the primary auditory cortex of Mongolian gerbils. By applying an algorithm for contour calculation, three distinct mid and four late evoked sinks were identified in layers I, III, Va, VIa, and VIb. Our results further showed that the patterns of intracortical information-flow remained qualitatively similar for low and for high sound pressure level stimuli at the characteristic frequency (CF) as well as for stimuli +/- 1 octave from CF. There were, however, differences associated with the strength, vertical extent, onset latency, and duration of the sinks for the four stimulation paradigms used. Stimuli one octave above the most sensitive frequency evoked a new, and quite reliable, sink in layer Va whereas low level stimulation led to the disappearance of the layer VIb sink. These data indicate the presence of input sources specifically activated in response to level and/or frequency parameters. Furthermore, spectral integration above vs. below the CF of neurons is asymmetric as illustrated by CSD profiles. These results are important because synaptic feedback associated with mid and late sinks-beginning at 50 ms post stimulus latency-is likely crucial for response modulation resulting from higher order processes like memory, learning or cognitive control. PMID- 26557060 TI - Dynamics of place, boundary and object encoding in rat anterior claustrum. AB - Discrete populations of brain cells signal differing types of spatial information. These "spatial cells" are largely confined to a closely-connected network of sites. We describe here, for the first time, cells in the anterior claustrum of the freely-moving rat encoding place, boundary and object information. This novel claustral spatial signal potentially directly modulates a wide variety of anterior cortical regions. We hypothesize that one of the functions of the claustrum is to provide information about body position, boundaries and landmark information, enabling dynamic control of behavior. PMID- 26557061 TI - Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps. AB - Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus (US) in a classical conditioning paradigm, where plant odors become associated with the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM) and one type of transcription-independent, anesthesia-resistant memory (ARM) can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE) genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In conclusion, these brain transcriptomes provide candidate genes that may be involved in the observed natural variation in LTM in closely related Cotesia parasitic wasp species. PMID- 26557062 TI - Infant attachment predicts bodily freezing in adolescence: evidence from a prospective longitudinal study. AB - Early life-stress, particularly maternal deprivation, is associated with long lasting deviations in animals' freezing responses. Given the relevance of freezing for stress-coping, translational research is needed to examine the relation between insecure infant-parent attachment and bodily freezing-like behavior in humans. Therefore, we investigated threat-related reductions in body sway (indicative of freezing-like behavior) in 14-year-old adolescents (N = 79), for whom attachment security was earlier assessed in infancy. As expected, insecure (vs. secure) attachment was associated with less body sway for angry vs. neutral faces. This effect remained when controlling for intermediate life events. These results suggest that the long-lasting effects of early negative caregiving experiences on the human stress and threat systems extend to the primary defensive reaction of freezing. Additionally, we replicated earlier work in adults, by observing a significant correlation (in adolescents assessed as securely attached) between subjective state anxiety and reduced body sway in response to angry vs. neutral faces. Together, this research opens venues to start exploring the role of freezing in the development of human psychopathology. PMID- 26557063 TI - Modulation of defensive reflex conditioning in snails by serotonin. AB - Highlights Daily injection of serotonin before a training session accelerated defensive reflex conditioning in snails.Daily injection of 5-hydroxytryptophan before a training session in snails with a deficiency of serotonin induced by the "neurotoxic" analog of serotonin 5,7-dihydroxytryptamine, restored the ability of snails to learn.After injection of the "neurotoxic" analogs of serotonin 5,6- and 5,7-dihydroxytryptamine as well as serotonin, depolarization of the membrane and decrease of the threshold potential of premotor interneurons was observed. We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the "neurotoxic" analogs of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within 2 weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail's ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3. PMID- 26557064 TI - A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series. AB - Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze (RAM) task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in multivariate patterns of voxel activity. PMID- 26557065 TI - Neuroplastic changes in resting-state functional connectivity after stroke rehabilitation. AB - Most neuroimaging research in stroke rehabilitation mainly focuses on the neural mechanisms underlying the natural history of post-stroke recovery. However, connectivity mapping from resting-state fMRI is well suited for different neurological conditions and provides a promising method to explore plastic changes for treatment-induced recovery from stroke. We examined the changes in resting-state functional connectivity (RS-FC) of the ipsilesional primary motor cortex (M1) in 10 post-acute stroke patients before and immediately after 4 weeks of robot-assisted bilateral arm therapy (RBAT). Motor performance, functional use of the affected arm, and daily function improved in all participants. Reduced interhemispheric RS-FC between the ipsilesional and contralesional M1 (M1-M1) and the contralesional-lateralized connections were noted before treatment. In contrast, greater M1-M1 functional connectivity and disturbed resting-state networks were observed after RBAT relative to pre-treatment. Increased changes in M1-M1 RS-FC after RBAT were coupled with better motor and functional improvements. Mediation analysis showed the pre-to-post difference in M1-M1 RS-FC was a significant mediator for the relationship between motor and functional recovery. These results show neuroplastic changes and functional recoveries induced by RBAT in post-acute stroke survivors and suggest that interhemispheric functional connectivity in the motor cortex may be a neurobiological marker for recovery after stroke rehabilitation. PMID- 26557066 TI - Comprehension through explanation as the interaction of the brain's coherence and cognitive control networks. AB - Discourse comprehension processes attempt to produce an elaborate and well connected representation in the reader's mind. A common network of regions including the angular gyrus, posterior cingulate, and dorsal frontal cortex appears to be involved in constructing coherent representations in a variety of tasks including social cognition tasks, narrative comprehension, and expository text comprehension. Reading strategies that require the construction of explicit inferences are used in the present research to examine how this coherence network interacts with other brain regions. A psychophysiological interaction analysis was used to examine regions showing changed functional connectivity with this coherence network when participants were engaged in either a non-inferencing reading strategy, paraphrasing, or a strategy requiring coherence-building inferences, self-explanation. Results of the analysis show that the coherence network increases in functional connectivity with a cognitive control network that may be specialized for the manipulation of semantic representations and the construction of new relations among these representations. PMID- 26557068 TI - Analysis of linear electrode array EMG for assessment of hemiparetic biceps brachii muscles. AB - This study presents a frequency analysis of surface electromyogram (EMG) signals acquired by a linear electrode array from the biceps brachii muscles bilaterally in 14 hemiparetic stroke subjects. For different levels of isometric contraction ranging from 10 to 80% of the maximum voluntary contraction (MVC), the power spectra of 19 bipolar surface EMG channels arranged proximally to distally along the muscle fibers were examined in both paretic and contralateral muscles. It was found that across all stroke subjects, the median frequency (MF) and the mean power frequency (MPF), averaged from different surface EMG channels, were significantly smaller in the paretic muscle compared to the contralateral muscle at each of the matched percent MVC contractions. The muscle fiber conduction velocity (MFCV) was significantly slower in the paretic muscle than in the contralateral muscle. No significant correlation between the averaged MF, MPF, or MFCV vs. torque was found in both paretic and contralateral muscles. However, there was a significant positive correlation between the global MFCV and MF. Examination of individual EMG channels showed that electrodes closest to the estimated muscle innervation zones produced surface EMG signals with significantly higher MF and MPF than more proximal or distal locations in both paretic and contralateral sides. These findings suggest complex central and peripheral neuromuscular alterations (such as selective loss of large motor units, disordered control of motor units, increased motor unit synchronization, and atrophy of muscle fibers, etc.) which can collectively influence the surface EMG signals. The frequency difference with regard to the innervation zone also confirms the relevance of electrode position in surface EMG analysis. PMID- 26557067 TI - The coordination dynamics of social neuromarkers. AB - Social behavior is a complex integrative function that entails many aspects of the brain's sensory, cognitive, emotional and movement capacities. Its neural processes are seldom simultaneous but occur according to precise spatiotemporal choreographies, manifested by the coordination of their oscillations within and between brains. Methods with good temporal resolution can help to identify so called "neuromarkers" of social function and aid in disentangling the dynamical architecture of social brains. In our ongoing research, we have used dual electroencephalography (EEG) to study neuromarker dynamics during synchronic interactions in which pairs of subjects coordinate behavior spontaneously and intentionally (social coordination) and during diachronic transactions that require subjects to perceive or behave in turn (action observation, delayed imitation). In this paper, after outlining our dynamical approach to the neurophysiological basis of social behavior, we examine commonalities and differences in the neuromarkers that are recruited for both kinds of tasks. We find the neuromarker landscape to be task-specific: synchronic paradigms of social coordination reveal medial mu, alpha and the phi complex as contributing neuromarkers. Diachronic tasks recruit alpha as well, in addition to lateral mu rhythms and the newly discovered nu and kappa rhythms whose functional significance is still unclear. Social coordination, observation, and delayed imitation share commonality of context: in each of our experiments, subjects exchanged information through visual perception and moved in similar ways. Nonetheless, there was little overlap between their neuromarkers, a result that hints strongly of task-specific neural mechanisms for social behavior. The only neuromarker that transcended both synchronic and diachronic social behaviors was the ubiquitous alpha rhythm, which appears to be a key signature of visually mediated social behaviors. The present paper is both an entry point and a challenge: much work remains to determine the nature and scope of recruitment of other neuromarkers, and to create theoretical models of their within- and between brain dynamics during social interaction. PMID- 26557070 TI - Serotonin receptor gene (HTR2A) T102C polymorphism modulates individuals' perspective taking ability and autistic-like traits. AB - Previous studies have indicated that empathic traits, such as perspective taking, are associated with the levels of serotonin in the brain and with autism spectrum conditions. Inspired by the finding that the serotonin receptor 2A gene (HTR2A) modulates the availability of serotonin, this study investigated to what extent HTR2A modulates individuals' perspective taking ability and autistic-like traits. To examine the associations of the functional HTR2A polymorphism T102C (rs6313) with individuals' perspective taking abilities and autistic-like traits, we differentiated individuals according to this polymorphism and measured empathic and autistic-like traits with Interpersonal Reactivity Index (IRI) and Autism Spectrum Quotient (AQ) scale in 523 Chinese people. The results indicated that this polymorphism was significantly associated with the scores on Perspective Taking and Personal Distress subscales of IRI, and Communication subscale of AQ. Individuals with a greater number of the C alleles were less likely to spontaneously adopt the point of view of others, more likely to be anxious when observing the pain endured by others, and more likely to have communication problems. Moreover, the genotype effect on communication problems was mediated by individuals' perspective taking ability. These findings provide evidence that the HTR2A T102C polymorphism is a predictor of individual differences in empathic and autistic-like traits and highlight the role of the gene in the connection between perspective taking and autistic-like traits. PMID- 26557069 TI - Identifying changes in EEG information transfer during drowsy driving by transfer entropy. AB - Drowsy driving is a major cause of automobile accidents. Previous studies used neuroimaging based approaches such as analysis of electroencephalogram (EEG) activities to understand the brain dynamics of different cortical regions during drowsy driving. However, the coupling between brain regions responding to this vigilance change is still unclear. To have a comprehensive understanding of neural mechanisms underlying drowsy driving, in this study we use transfer entropy, a model-free measure of effective connectivity based on information theory. We investigate the pattern of information transfer between brain regions when the vigilance level, which is derived from the driving performance, changes from alertness to drowsiness. Results show that the couplings between pairs of frontal, central, and parietal areas increased at the intermediate level of vigilance, which suggests that an enhancement of the cortico-cortical interaction is necessary to maintain the task performance and prevent behavioral lapses. Additionally, the occipital-related connectivity magnitudes monotonically decreases as the vigilance level declines, which further supports the cortical gating of sensory stimuli during drowsiness. Neurophysiological evidence of mutual relationships between brain regions measured by transfer entropy might enhance the understanding of cortico-cortical communication during drowsy driving. PMID- 26557071 TI - Modeling spatio-temporal dynamics of network damage and network recovery. AB - How networks endure damage is a central issue in neural network research. In this paper, we study the slow and fast dynamics of network damage and compare the results for two simple but very different models of recurrent and feed forward neural network. What we find is that a slower degree of network damage leads to a better chance of recovery in both types of network architecture. This is in accord with many experimental findings on the damage inflicted by strokes and by slowly growing tumors. Here, based on simulation results, we explain the seemingly paradoxical observation that disability caused by lesions, affecting large portions of tissue, may be less severe than the disability caused by smaller lesions, depending on the speed of lesion growth. PMID- 26557072 TI - Beauty and the Biologic: Artistic Documentation of Scientific Breakthrough in Psoriasis. AB - The making of wax moulages was an exclusive and sought-after art that was primarily used for teaching, but also to document clinical and laboratory research during the first half of the 20th century. Applying the technique of moulage-making to document a case of psoriasis improvement for posterity, a moulage of the trunk of a patient with psoriasis vulgaris was taken prior to treatment with biologics - adalimumab, a TNF-alpha antagonist - and again 3 month after adalimumab was first given. Our modern moulage shows in the most realistic way the science-driven improvement of psoriasis achievable nowadays with biologics. However, the real clinical picture of the disease is shrouded by showing only one detail of the patient - by accident the one with the best clinical improvement. All available techniques to document skin disease have advantages and limitations and nothing beats seeing live patients. PMID- 26557073 TI - Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature. AB - We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor) is discussed. PMID- 26557074 TI - Disseminated Cutaneous Leishmaniasis in Colombia: Report of 27 Cases. AB - Disseminated leishmaniasis (DL) is a poorly described disease that is frequently misdiagnosed as other clinical manifestations of cutaneous leishmaniasis (CL) such as diffuse CL or post-kala-azar dermal leishmaniasis. Twenty-seven cases of DL diagnosed between 1997 and 2015 are described. A higher prevalence was observed in men (mean age 32 years). The number of lesions per patient ranged from 12 to 294, distributed mainly in the upper extremities, face and trunk. The lesions were mostly plaques or nodules. Seven patients had nasal mucous damage, 74% of the patients were of mixed race, 92% lived in northwestern Colombia, and Leishmania (Viannia) panamensis was identified as the causative agent in 58% of cases. Eighteen patients recovered with pentavalent antimonial. The importance of distinguishing DL from those other clinical presentations is based on the fact that disseminated, diffuse and post-kala-azar CL are very different in etiology, clinical manifestations and response to treatment and prognosis. PMID- 26557075 TI - Koebner Phenomenon and Mycosis Fungoides. AB - Mycosis fungoides (MF) is the most frequent type of primary cutaneous T-cell/NK cell lymphoma. The Koebner phenomenon is defined as the appearance of cutaneous lesions on previously noninvolved skin following trauma and is observed in a series of cutaneous diseases including psoriasis, lichen planus, viral warts, molluscum contagiosum, etc. In this case report, 3 patients with longstanding MF are presented, the 1st with the appearance of a circumscribed early-stage type MF lesion rapidly following a surgical excision of an infundibular cyst, the 2nd with the appearance of a unique unilateral palmar tumoral MF lesion at the pressure site of a crutch, and the 3rd presented localized MF early stage lesions at the friction site of a belt. This report suggests that some MF patients may experience Koebner phenomenon-induced MF lesions and that MF should be added to the long list of skin diseases potentially exhibiting the Koebner phenomenon. PMID- 26557076 TI - Retroperitoneal Schwannoma in the Renal Hilum: A Case Report. AB - A 73-year-old male was referred to our department for further treatment of a right retroperitoneal tumor. Contrast CT showed a tumor mass measuring 33 * 26 mm in size with poor contrast enhancement. Because we were unable to rule out tumor malignancy, we planned an operation. The tumor was easily separated and removed without nephrectomy. Histological study revealed a schwannoma. It is rare for this kind of tumor to arise from the retroperitoneum (approximately 0.7% of all cases), in particular at the renal hilum. We herein report a rare case of retroperitoneal schwannoma arising from the renal hilum. PMID- 26557077 TI - Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi. AB - We report on a 79-year-old woman with staghorn calculi who presented with severe hypercalcemia. She was later found to have humoral hypercalcemia of malignancy caused by a rare tumor, squamous cell carcinoma of the renal pelvis. Chronic irritation, infection and inflammation from staghorn stones cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. The prognosis is very poor, with a 5-year survival rate of <10%. This case highlights the importance of awareness of a very rare and aggressive carcinoma in a patient with long-standing nephrolithiasis. PMID- 26557078 TI - Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman. AB - We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID- 26557079 TI - Endometrial Cancer with Sarcoidosis in Regional Lymph Nodes: A Case Report. AB - Sarcoidosis is a chronic, multisystemic disease commonly affecting the lungs and lymphatic system and is characterized by the formation of noncaseating granulomas. Although several reports are available on cases developing both sarcoidosis and cancer metachronously, cases of simultaneous diagnosis of these diseases have rarely been reported. A 67-year-old woman diagnosed with endometrial cancer had developed systemic lymph node swelling, including bilateral hilar, paraaortic, and a few pelvic lymph nodes, as observed on preoperative imaging. During surgery, frozen sections of a paraaortic lymph node were examined, revealing noncaseating granulomas compatible with sarcoidosis. Next, modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy were performed. Postoperative pathological analysis revealed endometrioid adenocarcinoma of the uterus, and no metastasis but noncaseating granulomas were detected in the resected lymph nodes. Postoperatively, we identified cutaneous sarcoidosis and uveitis in the presence of a tuberculin negative test. On the basis of these findings, we diagnosed the patients with endometrial cancer complicated by sarcoidosis. She underwent adjuvant chemotherapy, and at the 1-year follow-up, the lymph node swelling due to sarcoidosis was stable, and no recurrence of the cancer was observed. This turned out to be a case of early endometrial cancer mimicking advanced cancer by sarcoidosis. Histological confirmation and additional examination for sarcoidosis are necessary in cancer patients suspected of sarcoidosis. PMID- 26557080 TI - Long-Term Survival of a Patient with Metastatic Small-Cell Carcinoma of the Stomach Treated with Radiation Therapy. AB - Small-cell carcinoma (SCC), or high-grade neuroendocrine carcinoma of the stomach, is a rare subtype of extra-pulmonary SCC which is almost invariably lethal. Gastric SCC often presents with local symptoms indistinguishable from other primary stomach cancers; however, both regional and distant spread are common at the initial presentation. Depending on symptoms and patient performance status, treatment typically consists of chemotherapy or resection followed by adjuvant chemotherapy, as even patients with limited stage gastric SCC likely have micrometastatic disease at the time of diagnosis. In this case report, we describe the long-term survival of a 75-year-old male with recurrent oligometastatic high-grade neuroendocrine carcinoma of the stomach treated with radiation therapy (RT) alone. He presented with abdominal pain and dyspepsia and was found to have a 6 cm locally invasive node-positive gastric SCC initially treated with extensive surgical resection. He was not a candidate for adjuvant chemotherapy, and surveillance imaging subsequently confirmed metachronous liver and local recurrences within 1 year after surgery, which were managed with stereotactic body RT and conventional radiation, respectively. An additional para aortic nodal recurrence was treated with intensity-modulated radiotherapy 7 years after surgery with good response. He tolerated all RT courses without notable radiation-related toxicity and remains in complete remission 11 years after initial diagnosis. PMID- 26557081 TI - A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome. AB - Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM. PMID- 26557082 TI - Refractory Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient: Paradoxical Antifungal Therapy-Induced Clinical Deterioration Related to an Immune Response to Cryptococcal Organisms. AB - We present a case of refractory Cryptococcus neoformans meningoencephalitis in an immunocompetent woman. Her clinical symptoms did not improve with 6 months of antifungal therapy, and MRI abnormalities, indicating severe meningeal and cerebral inflammation, persisted despite a decreasing cryptococcal antigen titer. The patient continued to deteriorate despite antifungal therapy, and her condition clearly improved following treatment with adjunctive corticosteroid. We postulate that the paradoxical antifungal therapy-related clinical deterioration was due to an immune response to cryptococcal organisms, which responded to corticosteroids. These observations provide rationale for a further evaluation of corticosteroids in the management of select cases of C. neoformans central nervous system infection. PMID- 26557083 TI - Photoreceptor Outer Segment on Internal Limiting Membrane after Macular Hole Surgery: Implications for Pathogenesis. AB - PURPOSE: This report presents a case, which highlights key principles in the pathophysiology of macular holes. It has been hypothesized that anteroposterior (AP) and tangential vitreous traction on the fovea are the primary underlying factors causing macular holes [Nischal and Pearson; in Kanski and Bowling: Clinical Ophthalmology: A Systemic Approach, 2011, pp 629-631]. Spectral domain optical coherence tomography (OCT) has subsequently corroborated this theory in part but shown that AP vitreofoveal traction is the more common scenario [Steel and Lotery: Eye 2013;27:1-21]. METHODS: This study was conducted as a single case report. RESULTS: A 63-year old female presented to her optician with blurred and distorted vision in her left eye. OCT showed a macular hole with a minimum linear diameter of 370 um, with persistent broad vitreofoveal attachment on both sides of the hole edges. The patient underwent combined left phacoemulsification and pars plana vitrectomy, internal limiting membrane (ILM) peel and gas injection. The ILM was examined by electron microscopy and showed the presence of a cone outer segment on the retinal side. Post-operative OCT at 11 weeks showed a closed hole with recovery of the foveal contour and good vision. CONCLUSION: Our case shows the presence of a photoreceptor outer segment on the retinal side of the ILM and reinforces the importance of tangential traction in the development of some macula holes. The case highlights the theory of transmission of inner retinal forces to the photoreceptors via Muller cells and how a full thickness macular hole defect can occur in the absence of AP vitreomacular traction. PMID- 26557084 TI - Primary Vitreoretinal Lymphoma Masquerading as Refractory Retinitis. AB - PURPOSE: To report a case of a patient with primary vitreoretinal lymphoma masquerading as retinitis. METHODS: Retrospective review of the patient's clinical, histopathological and imaging records. RESULTS: Cytopathology was negative for malignancy, and preliminary polymerase chain reaction results supported the diagnosis of varicella zoster virus retinitis. Therefore, the patient was treated with antiviral therapy. However, under this treatment, the retinitis progressed. As a result, primary vitreoretinal lymphoma was suspected, and empirical treatment with intravitreal methotrexate injections was started. Under this treatment, the ocular features improved. Five months after initial ocular presentation and ocular resolution, the patient presented with central nervous system lymphoma. CONCLUSION: This case should raise the awareness of the variable clinical presentations, the challenging diagnosis and treatment of primary vitreoretinal lymphoma. All cases should be continuously systemically evaluated. PMID- 26557085 TI - Distinct synaptic and neurochemical changes to the granule cell-CA3 projection in Bassoon mutant mice. AB - Proper synaptic function depends on a finely-tuned balance between events such as protein synthesis and structural organization. In particular, the functional loss of just one synaptic-related protein can have a profound impact on overall neuronal network function. To this end, we used a mutant mouse model harboring a mutated form of the presynaptic scaffolding protein Bassoon (Bsn), which is phenotypically characterized by: (i) spontaneous generalized epileptic seizure activity, representing a chronically-imbalanced neuronal network; and (ii) a dramatic increase in hippocampal brain-derived neurotrophic factor (BDNF) protein concentration, a key player in synaptic plasticity. Detailed morphological and neurochemical analyses revealed that the increased BDNF levels are associated with: (i) modified neuropeptide distribution; (ii) perturbed expression of selected markers of synaptic activation or plasticity; (iii) subtle changes to microglial structure; and (iv) morphological alterations to the mossy fiber (MF) synapse. These findings emphasize the important contribution of Bassoon protein to normal hippocampal function, and further characterize the Bsn-mutant as a useful model for studying the effects of chronic changes to network activity. PMID- 26557086 TI - The roles of lipid and glucose metabolism in modulation of beta-amyloid, tau, and neurodegeneration in the pathogenesis of Alzheimer disease. AB - Diabetes is a risk factor for Alzheimer disease (AD). Apolipoprotein E (ApoE) and several genes related to AD have recently been identified by genome-wide association studies (GWAS) as being closely linked to lipid metabolism. Lipid metabolism and glucose-energy metabolism are closely related. Here, we review the emerging evidence regarding the roles of lipid and glucose metabolism in the modulation of beta-amyloid, tau, and neurodegeneration during the pathogenesis of AD. Disruption of homeostasis of lipid and glucose metabolism affects production and clearance of beta-amyloid and tau phosphorylation, and induces neurodegeneration. A more integrated understanding of the interactions among lipid, glucose, and protein metabolism is required to elucidate the pathogenesis of AD and to develop next-generation therapeutic options. PMID- 26557087 TI - Inflammatory stress potentiates emodin-induced liver injury in rats. AB - Herbal medicines containing emodin, widely used for the treatment of hepatitis in clinic, have been reported with hepatotoxicity in individuals. A modest inflammatory stress potentiating liver injury has been linked to the idiosyncratic drug-induced liver injury (IDILI). In this study, we investigated the hypothesis that lipopolysaccharide (LPS) interacts with emodin could synergize to cause liver injury in rats. Emodin (ranging from 20, 40, to 80 mg/kg), which is in the range of liver protection, was administered to rats, before LPS (2.8 mg/kg) or saline vehicle treatment. The biochemical tests showed that non-toxic dosage of LPS coupled with emodin caused significant increases of plasma ALT and AST activities as compared to emodin alone treated groups (P < 0.05). In addition, with LPS or emodin alone could not induce any changes in ALT and AST activity, as compared with the control group (0.5% CMC-Na treatment). Meanwhile, the plasma proinflammatory cytokines, TNF-alpha, IL-1beta, and IL-6 increased significantly in the emodin/LPS groups compared to either emodin groups or the LPS (P < 0.05). Histological analysis showed that liver damage was only found in emodin/LPS cotreatmented rat livers samples. These results indicate that non-toxic dosage of LPS potentiates the hepatotoxicity of emodin. This discovery raises the possibility that emodin and herbal medicines containing it may induce liver injury in the inflammatory stress even in their therapeutic dosages. PMID- 26557089 TI - Mechanical stretch-induced vascular hypertrophy occurs through modulation of leptin synthesis-mediated ROS formation and GATA-4 nuclear translocation. AB - BACKGROUND: Obesity and hypertension are associated with increased leptin production contributing to cardiovascular remodeling. Mechanisms involving mechanical stretch-induced leptin production and the cross talk between signaling pathways leading to vascular remodeling have not been fully elucidated. METHODS AND RESULTS: Rat portal vein (RPV) organ culture was used to investigate the effect of mechanical stretch on leptin protein expression in vascular smooth muscle cells (VSMCs). Moreover, the involvement of reactive oxygen species (ROS), the RhoA/ROCK pathway, actin cytoskeleton dynamics and the transcriptional factor GATA-4 activation in mechanical stretch-induced vascular remodeling were investigated. Stretching the RPV for 1 or 24 h significantly increased leptin protein level and ROS formation in VSMCs, which was prevented by 1 h pretreatment with the ROCK inhibitor Y-27632 and the actin cytoskeleton depolymerization agent cytochalasin D. Moreover, Western blotting and immunohistochemistry revealed that mechanical stretch or treatment with 3.1 nmol/L leptin for 24 h significantly increased actin polymerization, as reflected by an increase in the F-actin to G actin ratio. Increases in blood vessels' wet weight and [(3)H]-leucine incorporation following a 24 h treatment with conditioned media from cultured stretched RPVs indicated RPV hypertrophy. This effect was prevented by 1 h pretreatment with anti-leptin antibody, indicating leptin's crucial role in promoting VSMC hypertrophy. As an index of GATA-4 activation, GATA-4 nuclear translocation was assessed by immunohistochemistry method. Pretreating VSMC with leptin for 1 h significantly activated GATA-4 nuclear translocation, which was potently attenuated by the NADPH oxidase inhibitor apocynin, Y-27632, and cytochalasin D. CONCLUSION: Our results demonstrate that ROS formation, RhoA/ROCK pathway, and GATA-4 activation play a pivotal role in mechanical stretch-induced leptin synthesis leading to VSMC remodeling. PMID- 26557088 TI - Chemotherapy-induced peripheral neurotoxicity and complementary and alternative medicines: progress and perspective. AB - Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe and dose limiting side effect of antineoplastic drugs. It can cause sensory, motor and autonomic system dysfunction, and ultimately force patients to discontinue chemotherapy. Until now, little is understood about CIPN and no consistent caring standard is available. Since CIPN is a multifactorial disease, the clinical efficacy of single pharmacological drugs is disappointing, prompting patients to seek alternative treatment options. Complementary and alternative medicines (CAMs), especially herbal medicines, are well known for their multifaceted implications and widely used in human health care. Up to date, several phytochemicals, plant extractions, and herbal formulas have been evaluated for their potential therapeutic benefit of preventing the onset and progression of CIPN in experimental models. Clinical acupuncture has also been shown to improve CIPN symptoms. In this review, we will give an outline of our current knowledge regrading the advanced research of CIPN, the role of CAMs in alleviating CIPN and possible lacunae in research that needs to be addressed. PMID- 26557090 TI - Management of bipolar depression with lamotrigine: an antiepileptic mood stabilizer. AB - The efficacy of lamotrigine in the treatment of focal epilepsies have already been reported in several case reports and open studies, which is thought to act by inhibiting glutamate release through voltage-sensitive sodium channels blockade and neuronal membrane stabilization. However, recent findings have also illustrated the importance of lamotrigine in alleviating the depressive symptoms of bipolar disorder, without causing mood destabilization or precipitating mania. Currently, no mood stabilizers are available having equal efficacy in the treatment of both mania and depression, two of which forms the extreme sides of the bipolar disorder. Lamotrigine, a well established anticonvulsant has received regulatory approval for the treatment and prevention of bipolar depression in more than 30 countries worldwide. Lamotrigine, acts through several molecular targets and overcomes the major limitation of other conventional antidepressants by stabilizing mood from "below baseline" thereby preventing switches to mania or episode acceleration, thus being effective for bipolar I disorder. Recent studies have also suggested that these observations could also be extended to patients with bipolar II disorder. Thus, lamotrigine may supposedly fulfill the unmet requirement for an effective depression mood stabilizer. PMID- 26557091 TI - HDL in sepsis - risk factor and therapeutic approach. AB - High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40-70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis. PMID- 26557093 TI - Biomimetically enhanced demineralized bone matrix for bone regenerative applications. AB - Demineralized bone matrix (DBM) is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically enhanced version of DBM (BE-DBM) using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro osteogenic extracellular matrix (ECM) within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs) with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice. PMID- 26557094 TI - SIRT1-dependent myoprotective effects of resveratrol on muscle injury induced by compression. AB - Our current understanding on the molecular mechanisms by which sustained compression induces skeletal muscle injury is very limited. This study aimed to test the hypothesis that activation of SIRT1 by the natural antioxidant resveratrol could deactivate apoptotic and catabolic signaling in skeletal muscle exposed to moderate compression. Two cycles of 6-h constant pressure at 100 mmHg was applied to the tibialis region of right, but not left hindlimbs of Sprague Dawley rats pre-treated with DMSO (vehicle control) or resveratrol with/without sirtinol. Skeletal muscle tissues lying underneath and spatially corresponding to the compressed sites were collected for analyses. Resveratrol prevented the compression-induced manifestations of pathohistological damages including elevations of the number of interstitial nuclei and area of interstitial space and ameliorated oxidative damages measured as 4-hydroxy-2-nonenal (4HNE) and nitrotyrosine in skeletal muscle. In parallel, resveratrol augmented the expression level and activity of SIRT1 and phosphorylation levels of Foxo3a and Akt while suppressed the increases in protein abundances of p53, Bax, MAFbx, and ubiquitin, enzymatic activities of caspase 3 and 20S proteasome, and apoptotic DNA fragmentation in the compressed muscle. These favorable myoprotective effects of resveratrol were diminished upon pharmacological blockade of SIRT1 by using sirtinol. These novel data support the hypothesis that the anti-apoptotic and anti-catabolic effects of resveratrol on compression injury in skeletal muscle required the action of SIRT1. PMID- 26557096 TI - Is Schizotypy per se a Suitable Endophenotype of Schizophrenia? - Do Not Forget to Distinguish Positive from Negative Facets. PMID- 26557095 TI - Fine particulate matter in acute exacerbation of COPD. AB - Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID- 26557092 TI - Satellite cells in human skeletal muscle plasticity. AB - Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models. PMID- 26557097 TI - Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning. AB - This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders. PMID- 26557098 TI - ADHD Rehabilitation through Video Gaming: A Systematic Review Using PRISMA Guidelines of the Current Findings and the Associated Risk of Bias. AB - Empirical research studies have highlighted the need to investigate whether video game can be useful as a tool within a neuropsychological rehabilitation program for attention deficit hyperactivity disorder (ADHD) patients. However, little is known about the possible gains that this kind of video game-based interventions can produce and even if these gains can be transferred to real life abilities. The present paper aims to uncover key information related to the use of video game in ADHD neuropsychological rehabilitation/intervention by focusing on its gains and its capability to transfer/generalize these gains to real life situation via a systematic review of the empirical literature. The PRISMA guidelines were adopted. Internet-based bibliographic searches were conducted via seven major electronic databases (i.e., PsycARTICLES, PsycINFO, Web of Science, Core Collection BIOSIS Citation Index, MEDLINE, SciELO Citation Index, and PubMed) to access studies examining the association between video game interventions in ADHD patients and behavioral and cognitive outcomes. A total of 14 empirical studies meeting the inclusion criteria were identified. The studies reported the attention, working memory, and the behavioral aspects as the main target of the intervention. Cognitive and behavioral gains were reported after the video game training (VGT). However, many bias related to the choice of outcome instruments, sampling and blindness of assessors, weaken the results power. Additional researches are important to clarify the effects and stability of the VGT programs, and an important effort should be made to construct better methods to assess improvements on everyday cognitive abilities and real world functioning. PMID- 26557099 TI - Hooked on a feeling: affective anti-smoking messages are more effective than cognitive messages at changing implicit evaluations of smoking. AB - Because implicit evaluations are thought to underlie many aspects of behavior, researchers have started looking for ways to change them. We examine whether and when persuasive messages alter strongly held implicit evaluations of smoking. In smokers, an affective anti-smoking message led to more negative implicit evaluations on four different implicit measures as compared to a cognitive anti smoking message which seemed to backfire. Additional analyses suggested that the observed effects were mediated by the feelings and emotions raised by the messages. In non-smokers, both the affective and cognitive message engendered slightly more negative implicit evaluations. We conclude that persuasive messages change implicit evaluations in a way that depends on properties of the message and of the participant. Thus, our data open new avenues for research directed at tailoring persuasive messages to change implicit evaluations. PMID- 26557100 TI - Are common names becoming less common? The rise in uniqueness and individualism in Japan. AB - We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual's psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common Chinese characters with uncommon pronunciations, which indicates an increase in individualism in Japan. PMID- 26557101 TI - Emotion recognition through static faces and moving bodies: a comparison between typically developed adults and individuals with high level of autistic traits. AB - We investigated whether the type of stimulus (pictures of static faces vs. body motion) contributes differently to the recognition of emotions. The performance (accuracy and response times) of 25 Low Autistic Traits (LAT group) young adults (21 males) and 20 young adults (16 males) with either High Autistic Traits or with High Functioning Autism Spectrum Disorder (HAT group) was compared in the recognition of four emotions (Happiness, Anger, Fear, and Sadness) either shown in static faces or conveyed by moving body patch-light displays (PLDs). Overall, HAT individuals were as accurate as LAT ones in perceiving emotions both with faces and with PLDs. Moreover, they correctly described non-emotional actions depicted by PLDs, indicating that they perceived the motion conveyed by the PLDs per se. For LAT participants, happiness proved to be the easiest emotion to be recognized: in line with previous studies we found a happy face advantage for faces, which for the first time was also found for bodies (happy body advantage). Furthermore, LAT participants recognized sadness better by static faces and fear by PLDs. This advantage for motion kinematics in the recognition of fear was not present in HAT participants, suggesting that (i) emotion recognition is not generally impaired in HAT individuals, (ii) the cues exploited for emotion recognition by LAT and HAT groups are not always the same. These findings are discussed against the background of emotional processing in typically and atypically developed individuals. PMID- 26557102 TI - Who is respectful? Effects of social context and individual empathic ability on ambiguity resolution during utterance comprehension. AB - Verbal communication is often ambiguous. By employing the event-related potential (ERP) technique, this study investigated how a comprehender resolves referential ambiguity by using information concerning the social status of communicators. Participants read a conversational scenario which included a minimal conversational context describing a speaker and two other persons of the same or different social status and a directly quoted utterance. A singular, second person pronoun in the respectful form (nin/nin-de in Chinese) in the utterance could be ambiguous with respect to which of the two persons was the addressee (the "Ambiguous condition"). Alternatively, the pronoun was not ambiguous either because one of the two persons was of higher social status and hence should be the addressee according to social convention (the "Status condition") or because a word referring to the status of a person was additionally inserted before the pronoun to help indicate the referent of the pronoun (the "Referent condition"). Results showed that the perceived ambiguity decreased over the Ambiguous, Status, and Referent conditions. Electrophysiologically, the pronoun elicited an increased N400 in the Referent than in the Status and the Ambiguous conditions, reflecting an increased integration demand due to the necessity of linking the pronoun to both its antecedent and the status word. Relative to the Referent condition, a late, sustained positivity was elicited for the Status condition starting from 600 ms, while a more delayed, anterior negativity was elicited for the Ambiguous condition. Moreover, the N400 effect was modulated by individuals' sensitivity to the social status information, while the late positivity effect was modulated by individuals' empathic ability. These findings highlight the neurocognitive flexibility of contextual bias in referential processing during utterance comprehension. PMID- 26557103 TI - Do long delay conditioned stimuli develop inhibitory properties? AB - In long-delay conditioning, a long conditioned stimulus (CS) is paired in its final segments with an unconditioned stimulus. With sufficient training, this procedure usually results in conditioned responding being delayed until the final segment of the CS, a pattern of responding known as inhibition of delay. However, there have been no systematic investigations of the associative structure of long delay conditioning, and whether the initial segment of a long delay CS actually becomes inhibitory is debatable. In an appetitive preparation with rat subjects, the initial segment of long delay CS A passed a retardation (Experiment 1a) but not a summation (Experiment 1b) test for conditioned inhibition. Furthermore, retardation was observed only if long delay conditioning and retardation training occurred in the same context (Experiment 2). Thus, the initial segment of a long delay CS appears to share more characteristics with a latent inhibitor than a conditioned inhibitor. Componential theories of conditioning appear best suited to account for these results. PMID- 26557106 TI - Water surface tension modulates the swarming mechanics of Bacillus subtilis. AB - Many Bacillus subtilis strains swarm, often forming colonies with tendrils on agar medium. It is known that B. subtilis swarming requires flagella and a biosurfactant, surfactin. In this study, we find that water surface tension plays a role in swarming dynamics. B. subtilis colonies were found to contain water, and when a low amount of surfactin is produced, the water surface tension of the colony restricts expansion, causing bacterial density to rise. The increased density induces a quorum sensing response that leads to heightened production of surfactin, which then weakens water surface tension to allow colony expansion. When the barrier formed by water surface tension is breached at a specific location, a stream of bacteria swarms out of the colony to form a tendril. If a B. subtilis strain produces surfactin at levels that can substantially weaken the overall water surface tension of the colony, water floods the agar surface in a thin layer, within which bacteria swarm and migrate rapidly. This study sheds light on the role of water surface tension in regulating B. subtilis swarming, and provides insight into the mechanisms underlying swarming initiation and tendril formation. PMID- 26557105 TI - High Cholesterol Deteriorates Bone Health: New Insights into Molecular Mechanisms. AB - Many epidemiological studies show a positive connection between cardiovascular diseases and risk of osteoporosis, suggesting a role of hyperlipidemia and/or hypercholesterolemia in regulating osteoporosis. The majority of the studies indicated a correlation between high cholesterol and high LDL-cholesterol level with low bone mineral density, a strong predictor of osteoporosis. Similarly, bone metastasis is a serious complication of cancer for patients. Several epidemiological and basic studies have established that high cholesterol is associated with increased cancer risk. Moreover, osteoporotic bone environment predisposes the cancer cells for metastatic growth in the bone microenvironment. This review focuses on how cholesterol and cholesterol-lowering drugs (statins) regulate the functions of bone residential osteoblast and osteoclast cells to augment or to prevent bone deterioration. Moreover, this study provides an insight into molecular mechanisms of cholesterol-mediated bone deterioration. It also proposes a potential mechanism by which cellular cholesterol boosts cancer induced bone metastasis. PMID- 26557104 TI - The Role of Sleep and Sleep Disorders in the Development, Diagnosis, and Management of Neurocognitive Disorders. AB - It is becoming increasingly apparent that sleep plays an important role in the maintenance, disease prevention, repair, and restoration of both mind and body. The sleep and wake cycles are controlled by the pacemaker activity of the superchiasmic nucleus in the hypothalamus but can be disrupted by diseases of the nervous system causing disordered sleep. A lack of sleep has been associated with an increase in all-cause mortality. Likewise, sleep disturbances and sleep disorders may disrupt neuronal pathways and have an impact on neurological diseases. Sleep deprivation studies in normal subjects demonstrate that a lack of sleep can cause attention and working memory impairment. Moreover, untreated sleep disturbances and sleep disorders such as obstructive sleep apnoe (OSA) can also lead to cognitive impairment. Poor sleep and sleep disorders may present a significant risk factor for the development of dementia. In this review, the underlying mechanisms and the role of sleep and sleep disorders in the development of neurocognitive disorders [dementia and mild cognitive impairment (MCI)] and how the presence of sleep disorders could direct the process of diagnosis and management of neurocognitive disorders will be discussed. PMID- 26557107 TI - Variation in fungal microbiome (mycobiome) and aflatoxin in stored in-shell peanuts at four different areas of China. AB - The contamination of peanuts with Aspergillus sp. and subsequently aflatoxins is considered to be one of the most serious safety problems in the world. Mycobiome in peanuts is critical for aflatoxin production and food safety. To evaluate the biodiversity and ecological characteristics of whole communities in stored peanuts, the barcoded Illumina paired-end sequencing of the internal transcribed spacer 2 (ITS2) region of rDNA was used to characterize the peanut mycobiome monthly over a period of 1 year at four main peanut grown areas, i.e., Liaoning (LN, North East), Shandong (SD, East), Hubei (HB, Central), and Guangdong (GD, South) provinces. The fungal diversity of peanuts stored in SD was the highest with 98 OTUs and 43 genera, followed by LN, HB and GD. In peanuts stored in SD, Rhizopus, Emericella, and Clonostachys were predominant. In peanuts from LN, Penicillium, Eurotium, and Clonostachys were abundant. In peanuts from HB, Penicillium, Eurotium, and Aspergillus were higher. In GD peanuts, Eurotium, Aspergillus, and Emericella were mainly seen. The abundances of Aspergillus in LN, SD, HB, and GD were 0.53, 6.29, 10.86, and 25.75%, respectively. From the North of China to the South, that increased over the latitude, suggesting that the higher temperature and relative humidity might increase the risk of peanuts contaminated with Aspergillus and aflatoxins. During the storage, Aspergillus levels were higher at 7-12 months than in 0-6 months, suggesting that the risk increases over storage time. At 7-10 months, AFB1 was higher in four areas, while declined further. The reduction of AFB1 might be attributed to the inhibition and degradation of AFB1 by Aspergillus niger or to the combination with the compounds of peanuts. This is the first study that identified the mycobiome and its variation in stored peanuts using ITS2 sequencing technology, and provides the basis for a detailed characterization of whole mycobiome in peanuts. PMID- 26557108 TI - Genome analysis of orf virus isolates from goats in the Fujian Province of southern China. AB - Orf virus (ORFV), a species of the genus Parapoxvirus of the family Poxviridae, causes non-systemic, highly contagious, and eruptive disease in sheep, goat, and other wild and domestic ruminants. Our previous work shows orf to be ubiquitous in the Fujian Province of China, a region where there is considerable heterogeneity among ORFVs. In this study, we sequenced full genomes of four Fujian goat ORFV strains (OV-GO, OV-YX, OV-NP, and OV-SJ1). The four strains were 132-139 kb in length, with each containing 124-132 genes and about 64% G+C content. The most notable differences between the four strains were found near the genome termini. OV-NP lacked seven and OV-SJ1 lacked three genes near the right terminus when compared against other ORFVs. We also investigated the skin virulence of the four Fujian ORFVs in goats. The ORFVs with gene deletions showed low virulence while the ORFVs without gene deletions showed high virulence in goats suggesting gene deletion possibly leads to attenuation of ORFVs. Gene 134 was disrupted in OV-NP genome due to the lack of initial code. The phylogenetic tree based on complete Parapoxviruse genomes showed that sheep originated and goat originated ORFVs formed distinctly separate branches with 100% bootstrap. Based on the single gene phylogenetic tree of 132 genes of ORFVs, 47 genes can be easily distinguished as having originated from sheep or goats. In order to further reveal genetic variation presented in goat ORFVs and sheep ORFVs, we analyzed the deduced amino acid sequences of gene 008, multiple alignment of amino acid sequences of gene 008 from the genome of five goat ORFVs and four sheep ORFVs revealed 33 unique amino acids differentiating it as having sheep or goats as host. The availability of genomic sequences of four Fujian goat ORFVs aids in our understanding of the diversity of orf virus isolates in this region and can assist in distinguishing between orf strains that originate in sheep and goats. PMID- 26557109 TI - Controlling of CSFV in European wild boar using oral vaccination: a review. AB - Classical swine fever (CSF) is among the most detrimental diseases for the swine industry worldwide. Infected wild boar populations can play a crucial role in CSF epidemiology and controlling wild reservoirs is of utmost importance for preventing domestic outbreaks. Oral mass vaccination (OMV) has been implemented to control CSF in wild boars and limit the spill over to domestic pigs. This retrospective overview of vaccination experiences illustrates the potential for that option. The C-strain live vaccine was confirmed to be highly efficacious and palatable baits were developed for oral delivery in free ranging wild boars. The first field trials were performed in Germany in the 1990's and allowed deploying oral baits at a large scale. The delivery process was further improved during the 2000's among different European countries. Optimal deployment has to be early regarding disease emergence and correctly designed regarding the landscape structure and the natural food sources that can compete with oral baits. OMV deployment is also highly dependent on a local veterinary support working closely with hunters, wildlife and forestry agencies. Vaccination has been the most efficient strategy for CSF control in free ranging wild boar when vaccination is wide spread and lasting for a sufficient period of time. Alternative disease control strategies such as intensified hunting or creating physical boundaries such as fences have been, in contrast, seldom satisfactory and reliable. However, monitoring outbreaks has been challenging during and after vaccination deployment since OMV results in a low probability to detect virus-positive animals and the live-vaccine currently available does not allow serological differentiation of infected from vaccinated animals. The development of a new marker vaccine and companion test is thus a promising option for better monitoring outbreaks during OMV deployment as well as help to better determine when to stop vaccination efforts. After rabies in red fox, the use of OMV against CSF in European wild boar can be considered as a second example of successful disease control in wildlife. The 30 years of disease control experience included in this review may provide options for improving future disease management within wild populations. PMID- 26557110 TI - Fungal diversity in grape must and wine fermentation assessed by massive sequencing, quantitative PCR and DGGE. AB - The diversity of fungi in grape must and during wine fermentation was investigated in this study by culture-dependent and culture-independent techniques. Carignan and Grenache grapes were harvested from three vineyards in the Priorat region (Spain) in 2012, and nine samples were selected from the grape must after crushing and during wine fermentation. From culture-dependent techniques, 362 isolates were randomly selected and identified by 5.8S-ITS-RFLP and 26S-D1/D2 sequencing. Meanwhile, genomic DNA was extracted directly from the nine samples and analyzed by qPCR, DGGE and massive sequencing. The results indicated that grape must after crushing harbored a high species richness of fungi with Aspergillus tubingensis, Aureobasidium pullulans, or Starmerella bacillaris as the dominant species. As fermentation proceeded, the species richness decreased, and yeasts such as Hanseniaspora uvarum, Starmerella bacillaris and Saccharomyces cerevisiae successively occupied the must samples. The "terroir" characteristics of the fungus population are more related to the location of the vineyard than to grape variety. Sulfur dioxide treatment caused a low effect on yeast diversity by similarity analysis. Because of the existence of large population of fungi on grape berries, massive sequencing was more appropriate to understand the fungal community in grape must after crushing than the other techniques used in this study. Suitable target sequences and databases were necessary for accurate evaluation of the community and the identification of species by the 454 pyrosequencing of amplicons. PMID- 26557112 TI - High genetic similarity of ciprofloxacin-resistant Campylobacter jejuni in central Europe. AB - Campylobacteriosis is the leading zoonosis in the European Union with the majority of cases attributed to Campylobacter jejuni. Although the disease is usually self-limiting, some severe cases need to be treated with antibiotics, primarily macrolides and quinolones. However, the resistance to the latter is reaching alarming levels in most of the EU countries. To shed light on the expansion of antibiotic resistance in central Europe, we have investigated genetic similarity across 178 ciprofloxacin-resistant C. jejuni mostly isolated in Slovenia, Austria and Germany. We performed comparative genetic similarity analyses using allelic types of seven multilocus sequence typing housekeeping genes, and single nucleotide polymorphisms of a quinolone resistance determining region located within the DNA gyrase subunit A gene. This analysis revealed high genetic similarity of isolates from clonal complex ST-21 that carry gyrA allelic type 1 in all three of these central-European countries, suggesting these ciprofloxacin resistant isolates arose from a recent common ancestor and are spread clonally. PMID- 26557113 TI - New reassortant H5N8 highly pathogenic avian influenza virus from waterfowl in Southern China. AB - New reassortant H5N8 highly pathogenic avian influenza viruses were isolated from waterfowl in Southern China. Blast analysis demonstrated that the PB2 gene in these viruses were most closely related to A/wild duck/Shangdong/628/2011 (H5N1), while their NP genes were both more closely related to A/wild duck/Shandong/1/2011 (H5N1) and A/duck/Jiangsu/k1203/2010 (H5N8). However, the HA, NA, PB1, PA, M, and NS genes had the highest identity with A/duck/Jiangsu/k1203/2010 (H5N8). Phylogenetic analysis revealed that their HA genes belonged to the same GsGd H5 clade 2.3.4.4 detected in China in 2010. Therefore, we supposed that these H5N8 viruses might be novel reassortant viruses that have a H5N8 backbone while acquiring PB2 and NP genes from H5N1 viruses. This study is useful for better understanding the genetic and antigenic evolution of H5 avian influenza viruses in Southern China. PMID- 26557114 TI - Death and survival in Streptococcus mutans: differing outcomes of a quorum sensing signaling peptide. AB - Bacteria are considered "social" organisms able to communicate with one another using small hormone-like molecules (pheromones) in a process called quorum sensing (QS). These signaling molecules increase in concentration as a function of bacterial cell density. For most human pathogens, QS is critical for virulence and biofilm formation, and the opportunity to interfere with bacterial QS could provide a sophisticated means for manipulating the composition of pathogenic biofilms, and possibly eradicating the infection. Streptococcus mutans is a well characterized resident of the dental plaque biofilm, and is the major pathogen of dental caries (cavities). In S. mutans, its CSP QS signaling peptide does not act as a classical QS signal by accumulating passively in proportion to cell density. In fact, particular stresses such as those encountered in the oral cavity, induce the production of the CSP pheromone, suggesting that the pheromone most probably functions as a stress-inducible alarmone by triggering the signaling to the bacterial population to initiate an adaptive response that results in different phenotypic outcomes. This mini-review discusses two different CSP-induced phenotypes, bacterial "suicide" and dormancy, and the underlying mechanisms by which S. mutans utilizes the same QS signaling peptide to regulate two opposite phenotypes. PMID- 26557115 TI - Fluoroquinolone Resistance Mechanisms and population structure of Enterobacter cloacae non-susceptible to Ertapenem in North-Eastern France. AB - Fluoroquinolone (FQ) agents are a potential resort to treat infection due to Enterobacteriaceae producing extended spectrum beta-lactamase and susceptible to FQ. In a context of increase of non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 75 Enterobacter cloacae isolates non-susceptible to ertapenem in North-Eastern France in 2012 and describe the population structure by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Among them, 14.7% (12/75) carried a carbapenemase-encoding gene. Except one isolate producing VIM-1, the carbapenemase-producing isolates carried the well-known IncL/M pOXA48a plasmid. Most of the isolates (59/75) harbored at least a FQ-R determinant. qnr genes were predominant (40%, 30/75). The MLST study revealed that E. cloacae isolates' clonality was wide [24 different sequence types (STs)]. The more widespread STs were ST74, ST101, ST110, ST114, and ST133. Carbapenem MICs were higher for E. cloacae ST74 than for other E. cloacae isolates. Plasmid-mediated quinolone resistance determinants were more often observed in E. cloacae ST74 isolates. These findings showed that (i) pOXA-48a is spreading in North-Eastern France, (ii) qnr is preponderant in E. cloacae, (iii) E. cloacae comprised a large amount of lineages spreading in North-Eastern France, and (iv) FQ as an alternative to beta-lactams to treat ertapenem non-susceptible Enterobacteriaceae are compromised. PMID- 26557111 TI - The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders. AB - Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood-brain barrier into the CNS, where it has the ability to directly act on neurons and non neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments. PMID- 26557116 TI - The Role of Ion Channels in Microglial Activation and Proliferation - A Complex Interplay between Ligand-Gated Ion Channels, K(+) Channels, and Intracellular Ca(2.). AB - Microglia are often referred to as the immune cells of the brain. They are most definitely involved in immune responses to invading pathogens and inflammatory responses to tissue damage. However, recent results suggest microglia are vital for normal functioning of the brain. Neuroinflammation, as well as more subtle changes, in microglial function has been implicated in the pathogenesis of many brain diseases and disorders. Upon sensing alterations in their local environment, microglia change their shape and release factors that can modify the excitability of surrounding neurons. During neuroinflammation, microglia proliferate and release NO, reactive oxygen species, cytokines and chemokines. If inflammation resolves then their numbers normalize again via apoptosis. Microglia express a wide array of ion channels and different types are implicated in all of the cellular processes listed above. Modulation of microglial ion channels has shown great promise as a therapeutic strategy in several brain disorders. In this review, we discuss recent advances in our knowledge of microglial ion channels and their roles in responses of microglia to changes in the extracellular milieu. PMID- 26557118 TI - Extensive T-Cell Epitope Repertoire Sharing among Human Proteome, Gastrointestinal Microbiome, and Pathogenic Bacteria: Implications for the Definition of Self. AB - T-cell receptor binding to MHC-bound peptides plays a key role in discrimination between self and non-self. Only a subset, typically a pentamer, of amino acids in a MHC-bound peptide form the motif exposed to the T-cell receptor. We categorize and compare the T-cell exposed amino acid motif repertoire of the total proteomes of two groups of bacteria, comprising pathogens and gastrointestinal microbiome organisms, with the human proteome and immunoglobulins. Given the maximum 20(5), or 3.2 million of such motifs that bind T-cell receptors, there is considerable overlap in motif usage. We show that the human proteome, exclusive of immunoglobulins, only comprises three quarters of the possible motifs, of which 65.3% are also present in both composite bacterial proteomes. Very few motifs are unique to the human proteome. Immunoglobulin variable regions carry a broad diversity of T-cell exposed motifs (TCEMs) that provides a stratified random sample of the motifs found in pathogens, microbiome, and the human proteome. Individual bacterial genera and species vary in the content of immunoglobulin and human proteome matched motifs that they carry. Mycobacteria and Burkholderia spp carry a particularly high content of such matched motifs. Some bacteria retain a unique motif signature and motif sharing pattern with the human proteome. The implication is that distinguishing self from non-self does not depend on individual TCEMs, but on a complex and dynamic overlay of signals wherein the same TCEM may play different roles in different organisms, and the frequency with which a particular TCEM appears influences its effect. The patterns observed provide clues to bacterial immune evasion and to strategies for intervention, including vaccine design. The breadth and distinct frequency patterns of the immunoglobulin-derived peptides suggest a role of immunoglobulins in maintaining a broadly responsive T-cell repertoire. PMID- 26557119 TI - MHC and KIR Polymorphisms in Rhesus Macaque SIV Infection. AB - Natural killer lymphocytes are essentially involved as the first line of defense against agents such as viruses and malignant cells. The activity of these cells is regulated via interaction of specific and diverse killer cell immunoglobulin like receptors (KIR) with the highly polymorphic cognate MHC class I proteins on target cells. Genetic variability of both KIR and MHC-I ligands has been shown to be associated with resistance to many diseases, including infection with the immunodeficiency virus. Disease course and progression to AIDS after infection with human immunodeficiency virus-1 (HIV-1) is essentially influenced by the presence of the stimulatory KIR3DS1 receptor in combination with HLA-Bw4. Knowledge of such genetic interactions that contribute to not only disease resistance but also susceptibility are just as important. Such combined genetic factors were recently reported in the rhesus macaque AIDS model. Here, we review the rhesus macaque MHC class I and KIR gene systems and the role of their polymorphisms in the SIV infection model. PMID- 26557117 TI - Functional Specialization of Skin Dendritic Cell Subsets in Regulating T Cell Responses. AB - Dendritic cells (DC) are a heterogeneous family of professional antigen presenting cells classically recognized as most potent inducers of adaptive immune responses. In this respect, Langerhans cells have long been considered to be prototypic immunogenic DC in the skin. More recently this view has considerably changed. The generation of in vivo cell ablation and lineage tracing models revealed the complexity of the skin DC network and, in particular, established the existence of a number of phenotypically distinct Langerin(+) and negative DC populations in the dermis. Moreover, by now we appreciate that DC also exert important regulatory functions and are required for the maintenance of tolerance toward harmless foreign and self-antigens. This review summarizes our current understanding of the skin-resident DC system in the mouse and discusses emerging concepts on the functional specialization of the different skin DC subsets in regulating T cell responses. Special consideration is given to antigen cross-presentation as well as immune reactions toward contact sensitizers, cutaneous pathogens, and tumors. These studies form the basis for the manipulation of the human counterparts of the murine DC subsets to promote immunity or tolerance for the treatment of human disease. PMID- 26557120 TI - The Non-Obese Diabetic Mouse Strain as a Model to Study CD8(+) T Cell Function in Relapsing and Progressive Multiple Sclerosis. AB - Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4(+) T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8(+) T lymphocytes play a key role. Intriguingly, CD8(+) T cells accumulate in great numbers in the CNS in progressive MS, a form of the disease that is refractory to current disease-modifying therapies that target the CD4(+) T cell response. Here, we discuss the function of CD8(+) T cells in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In particular, we describe EAE in non-obese diabetic (NOD) background mice, which develop a pattern of disease characterized by multiple attacks and remissions followed by a progressively worsening phase. This is highly reminiscent of the pattern of disease observed in nearly half of MS patients. Particular attention is paid to a newly described transgenic mouse strain (1C6) on the NOD background whose CD4(+) and CD8(+) T cells are directed against the encephalitogenic peptide MOG[35-55]. Use of this model will give us a more complete picture of the role(s) played by distinct T cell subsets in CNS autoimmunity. PMID- 26557122 TI - Editorial: Causes for Increased Susceptibility to Mycobacterium tuberculosis - A Close View of the Immune System. PMID- 26557121 TI - An Overview of Challenges Limiting the Design of Protective Mucosal Vaccines for Finfish. AB - Research in mucosal vaccination in finfish has gained prominence in the last decade in pursuit of mucosal vaccines that would lengthen the duration of protective immunity in vaccinated fish. However, injectable vaccines have continued to dominate in the vaccination of finfish because they are perceived to be more protective than mucosal vaccines. Therefore, it has become important to identify the factors that limit developing protective mucosal vaccines in finfish as an overture to identifying key areas that require optimization in mucosal vaccine design. Some of the factors that limit the success for designing protective mucosal vaccines for finfish identified in this review include the lack optimized protective antigen doses for mucosal vaccines, absence of immunostimulants able to enhance the performance of non-replicative mucosal vaccines, reduction of systemic antibodies due to prolonged exposure to oral vaccination and the lack of predefined correlates of protective immunity for use in the optimization of newly developed mucosal vaccines. This review also points out the need to develop prime-boost vaccination regimes able to induce long-term protective immunity in vaccinated fish. By overcoming some of the obstacles identified herein, it is anticipated that future mucosal vaccines shall be designed to induce long-term protective immunity in finfish. PMID- 26557123 TI - Targeting CD8 T-Cell Metabolism in Transplantation. AB - Infiltration of effector CD8 T cells plays a major role in allograft rejection, and increases in memory and terminally differentiated effector memory CD8 T cells are associated with long-term allograft dysfunction. Alternatively, CD8 regulatory T cells suppress the inflammatory responses of effector lymphocytes and induce allograft tolerance in animal models. Recently, there has been a renewed interest in the field of immunometabolics and its important role in CD8 function and differentiation. The purpose of this review is to highlight the key metabolic pathways involved in CD8 T cells and to discuss how manipulating these metabolic pathways could lead to new immunosuppressive strategies for the transplantation field. PMID- 26557124 TI - TOR-inhibitor insensitive-1 (TRIN1) regulates cotyledons greening in Arabidopsis. AB - Target of Rapamycin (TOR) is an eukaryotic protein kinase and evolutionally conserved from the last eukaryotic common ancestor (LECA) to humans. The growing evidences have shown that TOR signaling acts as a central controller of cell growth and development. The downstream effectors of TOR have been well-identified in yeast and animals by using the immunosuppression agent rapamycin. However, less is known about TOR in plants. This is largely due to the fact that plants are insensitive to rapamycin. In this study, AZD8055 (AZD), the novel ATP competitive inhibitor of TOR, was employed to decipher the downstream effectors of TOR in Arabidopsis. One AZD insensitive mutant, T O R - i nhibitor i n sensitive- 1 (trin1), was screened from 10,000 EMS-induced mutation seeds. The cotyledons of trin1 can turn green when its seeds were germinated on 1/2 MS medium supplemented with 2 MUM AZD, whereas the cotyledons greening of wild-type (WT) can be completely blocked at this concentration. Through genetic mapping, TRIN1 was mapped onto the long arm of chromosome 2, between markers SGCSNP26 and MI277. Positional cloning revealed that TRIN1 was an allele of ABI4, which encoded an ABA-regulated AP2 domain transcription factor. Plants containing P35S::TRIN1 or P35S::TRIN1-GUS were hypersensitive to AZD treatment and displayed the opposite phenotype observed in trin1. Importantly, GUS signaling was significantly enhanced in P35S::TRIN1-GUS transgenic plants in response to AZD treatment, indicating that suppression of TOR resulted in the accumulation of TRIN1. These observations revealed that TOR controlled seed-to-seedling transition by negatively regulating the stability of TRIN1 in Arabidopsis. For the first time, TRIN1, the downstream effector of TOR signaling, was identified through a chemical genetics approach. PMID- 26557125 TI - Temporal analysis reveals a key role for VTE5 in vitamin E biosynthesis in olive fruit during on-tree development. AB - The aim of this work was to generate a high resolution temporal mapping of the biosynthetic pathway of vitamin E in olive fruit (Olea europaea cv. "Koroneiki") during 17 successive on-tree developmental stages. Fruit material was collected from the middle of June until the end of January, corresponding to 6-38 weeks after flowering (WAF). Results revealed a variable gene regulation pattern among 6-38 WAF studied and more pronounced levels of differential regulation of gene expression for the first and intermediate genes in the biosynthetic pathway (VTE5, geranylgeranyl reductase, HPPD, VTE2, HGGT and VTE3) compared with the downstream components of the pathway (VTE1 and VTE4). Notably, expression of HGGT and VTE2 genes were significantly suppressed throughout the developmental stages examined. Metabolite analysis indicated that the first and intermediate stages of development (6-22 WAF) have higher concentrations of tocochromanols compared with the last on-tree stages (starting from 24 WAF onwards). The concentration of alpha-tocopherol (16.15 +/- 0.60-32.45 +/- 0.54 mg/100 g F.W.) were substantially greater (up to 100-fold) than those of beta-, gamma-, and delta-tocopherols (0.13 +/- 0.01-0.25 +/- 0.03 mg/100 g F.W., 0.13 +/- 0.01-0.33 +/- 0.04 mg/100 g F.W., 0.14 +/- 0.01-0.28 +/- 0.01 mg/100 g F.W., respectively). In regard with tocotrienol content, only gamma-tocotrienol was detected. Overall, olive fruits (cv. "Koroneiki") exhibited higher concentrations of vitamin E until 22 WAF as compared with later WAF, concomitant with the expression profile of phytol kinase (VTE5), which could be used as a marker gene due to its importance in the biosynthesis of vitamin E. To the best of our knowledge, this is the first study that explores the complete biosynthetic pathway of vitamin E in a fruit tree crop of great horticultural importance such as olive, linking molecular gene expression analysis with tocochromanol content. PMID- 26557127 TI - Molecular evolution, characterization, and expression analysis of SnRK2 gene family in Pak-choi (Brassica rapa ssp. chinensis). AB - The sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family members are plant-specific serine/threonine kinases that are involved in the plant response to abiotic stress and abscisic acid (ABA)-dependent plant development. Further understanding of the evolutionary history and expression characteristics of these genes will help to elucidate the mechanisms of the stress tolerance in Pak-choi, an important green leafy vegetable in China. Thus, we investigated the evolutionary patterns, footprints and conservation of SnRK2 genes in selected plants and later cloned and analyzed SnRK2 genes in Pak-choi. We found that this gene family was preferentially retained in Brassicas after the Brassica Arabidopsis thaliana split. Next, we cloned and sequenced 13 SnRK2 from both cDNA and DNA libraries of stress-induced Pak-choi, which were under conditions of ABA, salinity, cold, heat, and osmotic treatments. Most of the BcSnRK2s have eight exons and could be divided into three groups. The subcellular localization predictions suggested that the putative BcSnRK2 proteins were enriched in the nucleus. The results of an analysis of the expression patterns of the BcSnRK2 genes showed that BcSnRK2 group III genes were robustly induced by ABA treatments. Most of the BcSnRK2 genes were activated by low temperature, and the BcSnRK2.6 genes responded to both ABA and low temperature. In fact, most of the BcSnRK2 genes showed positive or negative regulation under ABA and low temperature treatments, suggesting that they may be global regulators that function at the intersection of multiple signaling pathways to play important roles in Pak-choi stress responses. PMID- 26557126 TI - Repeat-containing protein effectors of plant-associated organisms. AB - Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs) that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms. PMID- 26557128 TI - A phylogenetic approach to study the origin and evolution of the CRINKLY4 family. AB - Cell-cell communication plays a crucial role in plant growth and development and relies to a large extent on peptide ligand-receptor kinase signaling mechanisms. The CRINKLY4 (CR4) family of receptor-like kinases is involved in a wide range of developmental processes in plants, including mediating columella stem cell identity and differentiation in the Arabidopsis thaliana root tip. Members of the CR4 family contain a signal peptide, an extracellular part, a single-pass transmembrane helix and an intracellular cytoplasmic protein kinase domain. The main distinguishing features of the family are the presence of seven "crinkly" repeats and a TUMOR NECROSIS FACTOR RECEPTOR (TNFR)-like domain in the extracellular part. Here, we investigated the evolutionary origin of the CR4 family and explored to what extent members of this family are conserved throughout the green lineage. We identified members of the CR4 family in various dicots and monocots, and also in the lycophyte Selaginella moellendorffii and the bryophyte Physcomitrella patens. In addition, we attempted to gain insight in the evolutionary origin of different CR4-specific domains, and we could detect "crinkly" repeat containing proteins already in single celled algae. Finally, we related the presence of likely functional CR4 orthologs to its best described signaling module comprising CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 40 (CLE40), WUSCHEL RELATED HOMEOBOX 5 (WOX5), CLAVATA 1 (CLV1), and ARABIDOPSIS CR4 (ACR4), and established that this module likely is already present in bryophytes and lycophytes. PMID- 26557129 TI - Evolution, diversification, and expression of KNOX proteins in plants. AB - The KNOX (KNOTTED1-like homeobox) transcription factors play a pivotal role in leaf and meristem development. The majority of these proteins are characterized by the KNOX1, KNOX2, ELK, and homeobox domains whereas the proteins of the KNATM family contain only the KNOX domains. We carried out an extensive inventory of these proteins and here report on a total of 394 KNOX proteins from 48 species. The land plant proteins fall into two classes (I and II) as previously shown where the class I family seems to be most closely related to the green algae homologs. The KNATM proteins are restricted to Eudicots and some species have multiple paralogs of this protein. Certain plants are characterized by a significant increase in the number of KNOX paralogs; one example is Glycine max. Through the analysis of public gene expression data we show that the class II proteins of this plant have a relatively broad expression specificity as compared to class I proteins, consistent with previous studies of other plants. In G. max, class I protein are mainly distributed in axis tissues and KNATM paralogs are overall poorly expressed; highest expression is in the early plumular axis. Overall, analysis of gene expression in G. max demonstrates clearly that the expansion in gene number is associated with functional diversification. PMID- 26557131 TI - Influence of low- and high-elevation plant genomes on the regulation of autumn cold acclimation in Abies sachalinensis. AB - Boreal coniferous species with wide geographic distributions show substantial variation in autumn cold acclimation among populations. To determine how this variation is inherited across generations, we conducted a progeny test and examined the development of cold hardening in open-pollinated second-generation (F2) progeny of Abies sachalinensis. The F1 parents had different genetic backgrounds resulting from reciprocal interpopulational crosses between low elevation (L) and high-elevation (H) populations: L * L, L * H, H * L, and H * H. Paternity analysis of the F2 progeny using molecular genetic markers showed that 91.3% of the fathers were located in surrounding stands of the F1 planting site (i.e., not in the F1 test population). The remaining fathers were assigned to F1 parents of the L * L cross-type. This indicates that the high-elevation genome in the F1 parents was not inherited by the F2 population via pollen flow. The timing of autumn cold acclimation in the F2 progeny depended on the cross-type of the F1 mother. The progeny of H * H mothers showed less damage in freezing tests than the progeny of other cross-types. Statistical modeling supported a linear effect of genome origin. In the best model, variation in freezing damage was explained by the proportion of maternally inherited high-elevation genome. These results suggest that autumn cold acclimation was partly explained by the additive effect of the responsible maternal genome. Thus, the offspring that inherited a greater proportion of the high-elevation genome developed cold hardiness earlier. Genome based variation in the regulation of autumn cold acclimation matched the local climatic conditions, which may be a key factor in elevation-dependent adaptation. PMID- 26557132 TI - The miRNAs and their regulatory networks responsible for pollen abortion in Ogura CMS Chinese cabbage revealed by high-throughput sequencing of miRNAs, degradomes, and transcriptomes. AB - Chinese cabbage (Brassica rapa ssp. pekinensis) is one of the most important vegetables in Asia and is cultivated across the world. Ogura-type cytoplasmic male sterility (Ogura-CMS) has been widely used in the hybrid breeding industry for Chinese cabbage and many other cruciferous vegetables. Although, the cause of Ogura-CMS has been localized to the orf138 locus in the mitochondrial genome, however, the mechanism by which nuclear genes respond to the mutation of the mitochondrial orf138 locus is unclear. In this study, a series of whole genome small RNA, degradome and transcriptome analyses were performed on both Ogura-CMS and its maintainer Chinese cabbage buds using deep sequencing technology. A total of 289 known miRNAs derived from 69 families (including 23 new families first reported in B. rapa) and 426 novel miRNAs were identified. Among these novel miRNAs, both 3-p and 5-p miRNAs were detected on the hairpin arms of 138 precursors. Ten known and 49 novel miRNAs were down-regulated, while one known and 27 novel miRNAs were up-regulated in Ogura-CMS buds compared to the fertile plants. Using degradome analysis, a total of 376 mRNAs were identified as targets of 30 known miRNA families and 100 novel miRNAs. A large fraction of the targets were annotated as reproductive development related. Our transcriptome profiling revealed that the expression of the targets was finely tuned by the miRNAs. Two novel miRNAs were identified that were specifically highly expressed in Ogura-CMS buds and sufficiently suppressed two pollen development essential genes: sucrose transporter SUC1 and H (+) -ATPase 6. These findings provide clues for the contribution of a potential miRNA regulatory network to bud development and pollen engenderation. This study contributes new insights to the communication between the mitochondria and chromosome and takes one step toward filling the gap in the regulatory network from the orf138 locus to pollen abortion in Ogura-CMS plants from a miRNA perspective. PMID- 26557133 TI - Natural variations in expression of regulatory and detoxification related genes under limiting phosphate and arsenate stress in Arabidopsis thaliana. AB - Abiotic stress including nutrient deficiency and heavy metal toxicity severely affects plant growth, development, and productivity. Genetic variations within and in between species are one of the important factors in establishing interactions and responses of plants with the environment. In the recent past, natural variations in Arabidopsis thaliana have been used to understand plant development and response toward different stresses at genetic level. Phosphorus deficiency negatively affects plant growth and metabolism and modulates expression of the genes involved in Pi homeostasis. Arsenate, As(V), a chemical analog of Pi, is taken up by the plants via phosphate transport system. Studies suggest that during Pi deficiency, enhanced As(V) uptake leads to increased toxicity in plants. Here, the natural variations in Arabidopsis have been utilized to study the As(V) stress response under limiting Pi condition. The primary root length was compared to identify differential response of three Arabidopsis accessions (Col-0, Sij-1, and Slavi-1) under limiting Pi and As(V) stress. To study the molecular mechanisms responsible for the differential response, comprehensive expression profiling of the genes involved in uptake, detoxification, and regulatory mechanisms was carried out. Analysis suggests genetic variation-dependent regulatory mechanisms may affect differential response of Arabidopsis natural variants toward As(V) stress under limiting Pi condition. Therefore, it is hypothesized that detailed analysis of the natural variations under multiple stress conditions might help in the better understanding of the biological processes involved in stress tolerance and adaptation. PMID- 26557130 TI - DNA damage and repair in plants - from models to crops. AB - The genomic integrity of every organism is constantly challenged by endogenous and exogenous DNA-damaging factors. Mutagenic agents cause reduced stability of plant genome and have a deleterious effect on development, and in the case of crop species lead to yield reduction. It is crucial for all organisms, including plants, to develop efficient mechanisms for maintenance of the genome integrity. DNA repair processes have been characterized in bacterial, fungal, and mammalian model systems. The description of these processes in plants, in contrast, was initiated relatively recently and has been focused largely on the model plant Arabidopsis thaliana. Consequently, our knowledge about DNA repair in plant genomes - particularly in the genomes of crop plants - is by far more limited. However, the relatively small size of the Arabidopsis genome, its rapid life cycle and availability of various transformation methods make this species an attractive model for the study of eukaryotic DNA repair mechanisms and mutagenesis. Moreover, abnormalities in DNA repair which proved to be lethal for animal models are tolerated in plant genomes, although sensitivity to DNA damaging agents is retained. Due to the high conservation of DNA repair processes and factors mediating them among eukaryotes, genes and proteins that have been identified in model species may serve to identify homologous sequences in other species, including crop plants, in which these mechanisms are poorly understood. Crop breeding programs have provided remarkable advances in food quality and yield over the last century. Although the human population is predicted to "peak" by 2050, further advances in yield will be required to feed this population. Breeding requires genetic diversity. The biological impact of any mutagenic agent used for the creation of genetic diversity depends on the chemical nature of the induced lesions and on the efficiency and accuracy of their repair. More recent targeted mutagenesis procedures also depend on host repair processes, with different pathways yielding different products. Enhanced understanding of DNA repair processes in plants will inform and accelerate the engineering of crop genomes via both traditional and targeted approaches. PMID- 26557134 TI - Effects of a Multicomponent Exercise Program on Spatiotemporal Gait Parameters, Risk of Falling and Physical Activity in Dementia Patients. AB - BACKGROUND: Exercise programs are presumed to rehabilitate gait disorders and to reduce the risk of falling in dementia patients. This study aimed to analyze the specific effects of multicomponent exercise on gait disorders and to determine the association between gait impairments and the risk of falling in dementia patients before and after intervention. METHODS: We conducted an 8-week multicomponent exercise program in 16 dementia patients (age 86.7 +/- 5.4 years). All participants were assessed several times for gait analysis (Locometrix(r)), Tinetti score and physical activity (Body Media SenseWear(r) Pro armband). RESULTS: After 8 weeks of the exercise program, the mean gait speed was 0.12 m/s faster than before the intervention (0.55 +/- 0.17 vs. 0.67 +/- 0.14 m/s). The multicomponent exercise program improved gait performance and Tinetti score (p < 0.05). Gait performance (gait speed, stride length) was correlated with the Tinetti score (p < 0.05). CONCLUSION: Analysis of spatiotemporal gait parameters using an accelerometer method provided a quick and easy tool to estimate the benefits of an exercise program and the risk of falling. PMID- 26557135 TI - A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease. AB - AIM: To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm(2) and titrated to 10 cm(2) after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm(2) and titrated by 2.5 cm(2) every 4 weeks to 10 cm(2)). METHODS: A 24 week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. RESULTS: Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was -3.6% (95% confidence interval: -17.0, 9.6), falling within the prespecified acceptance range. CONCLUSION: The tolerability of two different titration schemes was similar in Japanese patients with AD. PMID- 26557136 TI - Hypertensive Disorders of Pregnancy Appear Not to Be Associated with Alzheimer's Disease Later in Life. AB - BACKGROUND: After hypertensive disorders of pregnancy, more subjective cognitive complaints and white matter lesions are reported compared to women after normal pregnancies. Both have a causal relationship with Alzheimer's disease (AD). AIM: To investigate if women whose pregnancy was complicated by hypertensive disorders have an increased risk of AD. METHODS: A case-control study in women with AD from the Alzheimer Center of the VU University Medical Center Amsterdam and women without AD. Paper and telephone surveys were performed. RESULTS: The response rate was 85.2%. No relation between women with (n = 104) and without AD (n = 129) reporting pregnancies complicated by hypertensive disorders (p = 0.11) was found. Women with early-onset AD reported hypertensive disorders of pregnancy more often (p = 0.02) compared to women with late-onset AD. CONCLUSION: A reported history of hypertensive disorders of pregnancy appears not to be associated with AD later in life. PMID- 26557137 TI - Commentary: FTO obesity variant circuitry and adipocyte browning in humans. PMID- 26557138 TI - The bacterial and host factors associated with extrapulmonary dissemination of Mycobacterium tuberculosis. AB - With high morbidity and mortality worldwide, tuberculosis (TB) is still an important public health threat. The majority of human TB cases are caused by Mycobacterium tuberculosis. Although pulmonary TB is the most common presentation, M. tuberculosis can disseminate into other organs and causes extrapulmonary TB (EPTB). The dissemination of bacteria from the initial site of infection to other organs can lead to fatal diseases, such as miliary and meningeal TB. Thoroughly understanding the mechanisms and pathways of dissemination would develop therapies to prevent the lethal prognosis of EPTB (miliary and meningeal TB) and vaccines to promote the development of adaptive immunity. This review focuses on risk factors of EPTB, bacterial and host genes involved in EPTB, and potential mechanisms of M. tuberculosis extrapulmonary dissemination. PMID- 26557139 TI - A Neuroeconomics Analysis of Investment Process with Money Flow Information: The Error-Related Negativity. AB - This investigation is among the first ones to analyze the neural basis of an investment process with money flow information of financial market, using a simplified task where volunteers had to choose to buy or not to buy stocks based on the display of positive or negative money flow information. After choosing "to buy" or "not to buy," participants were presented with feedback. At the same time, event-related potentials (ERPs) were used to record investor's brain activity and capture the event-related negativity (ERN) and feedback-related negativity (FRN) components. The results of ERN suggested that there might be a higher risk and more conflict when buying stocks with negative net money flow information than positive net money flow information, and the inverse was also true for the "not to buy" stocks option. The FRN component evoked by the bad outcome of a decision was more negative than that by the good outcome, which reflected the difference between the values of the actual and expected outcome. From the research, we could further understand how investors perceived money flow information of financial market and the neural cognitive effect in investment process. PMID- 26557141 TI - Identification of Novel Inhibitors for Tobacco Mosaic Virus Infection in Solanaceae Plants. AB - Tobacco mosaic virus (TMV) infects several crops of economic importance (e.g., tomato) and remains as one of the major concerns to the farmers. TMV enters the host cell and produces the capping enzyme RNA polymerase. The viral genome replicates further to produce multiple mRNAs which encodes several proteins, including the coat protein and an RNA-dependent RNA polymerase (RdRp), as well as the movement protein. TMV replicase domain was chosen for the virtual screening studies against small molecules derived from ligand databases such as PubChem and ChemBank. Catalytic sites of the RdRp domain were identified and subjected to docking analysis with screened ligands derived from virtual screening LigandFit. Small molecules that interact with the target molecule at the catalytic domain region amino acids, GDD, were chosen as the best inhibitors for controlling the TMV replicase activity. PMID- 26557140 TI - Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China. AB - Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR. Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P < 0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04-90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07-69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31 15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings. PMID- 26557142 TI - Gynaecological Screening for Cervical and Vulvar Malignancies in a Cohort of Systemic Sclerosis Patients: Our Experience and Review of the Literature. AB - Background. Increased incidence of cancer was frequently reported in scleroderma (SSc), but no association with gynaecological malignancies was described in literature. Objectives. To investigate gynaecological neoplasms in SSc patients. Methods. In this cross-sectional analysis, we evaluated 80 SSc patients, living in the same geographical area. We considered all patients undergoing gynaecological evaluation, including pap test as screening for cervical cancer, between January 2008 and December 2014. Results. 55 (68.7%) patients were negative and 20 (25%) presented inflammatory alterations, while cancer or precancerous lesions were found in 5 (6.2%) cases (2 showed cervical cancer (one of them in situ), 1 vulvar melanoma, 1 vulvar intraepithelial neoplasia, and 1 endocervical polyp with immature squamous metaplasia). The frequency of cervical cancer in our series seems higher in comparison to the incidence registered in the same geographical area. The presence of atypical cytological findings correlated with anti-Scl70 autoantibodies (p = 0.022); moreover, the patients with these alterations tended to be older (median 65, range 46-67), if compared to the whole series (p = 0.052). Conclusions. A relatively high frequency of gynaecological malignancies was found in our SSc series. In general, gynaecological evaluation for SSc women needs to be included in the routine patients' surveillance. PMID- 26557143 TI - Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma. AB - Trachoma is caused by Chlamydia trachomatis and is a leading cause of blindness worldwide. Mass distribution of azithromycin (AZM) is part of the strategy for the global elimination of blinding trachoma by 2020. Although resistance to AZM in C. trachomatis has not been reported, there have been concerns about resistance in other organisms when AZM is administered in community settings. We identified studies that measured pneumococcal prevalence and resistance to AZM following mass AZM provision reported up to 2013 in Medline and Web of Science databases. Potential sources of bias were assessed using the Cochrane Risk of Bias Tool. A total of 45 records were screened, of which 8 met the inclusion criteria. We identified two distinct trends of resistance prevalence, which are dependent on frequency of AZM provision and baseline prevalence of resistance. We also demonstrated strong correlation between the prevalence of resistance at baseline and at 2-3 months (r = 0.759). Although resistance to AZM in C. trachomatis has not been reported, resistance to this commonly used macrolide antibiotic in other diseases could compromise treatment. This should be considered when planning long-term trachoma control strategies. PMID- 26557144 TI - Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins. AB - Scutellarin (SCU) is one of the main components of traditional Chinese medicine plant Erigeron breviscapus (Vant.) Hand.-Mazz. In this paper, we studied the protective effects of SCU on human cardiac microvascular endothelial cells (HCMECs) against hypoxia-reoxygenation (HR) injury and its possible target related proteins. Results of MTT assay showed that pretreatment of SCU at doses of 1, 5, and 10 MUM for 2 h could significantly inhibit the decrease in cell viability of HCMECs induced by HR injury. Subcellular fractions of cells treated with vehicle control, 1 MUM SCU, HR injury, or 1 MUM SCU + HR injury were separated by ultracentrifugation. The protein expression profiles of cytoplasm and membrane/nuclei fractions were checked using protein two-dimensional electrophoresis (2-DE). Proteins differentially expressed between control and SCU treated group, control and HR group, or HR and SCU + HR group were identified using mass spectrometry (MS/MS). Possible interaction network of these target related proteins was predicted using bioinformatic analysis. The influence of SCU on the expression levels of these proteins was confirmed using Western blotting assay. The results indicated that proteins such as p27BBP protein (EIF6), heat shock 60 kDa protein 1 (HSPD1), and chaperonin containing TCP1 subunit 6A isoform (CCT6A) might play important roles in the effects of SCU. PMID- 26557145 TI - Investigation on Molecular Mechanism of Fibroblast Regulation and the Treatment of Recurrent Oral Ulcer by Shuizhongcao Granule-Containing Serum. AB - The purpose is to study the intervention, proliferation, and differentiation on fibroblast by Shuizhongcao Granule during the treatment of ROU and investigate the action mechanism in inflammatory microenvironment. Proliferation of rat fibroblasts was detected using CCK8. Western blot was used to detect the effect of drug-containing serum on the expression of protein associated with NF-kappaB and ERK pathway in rat fibroblasts. Expression of IL-10 and IL-12 was detected by PCR. Shuizhongcao Granule group successfully inhibited proliferation of rat fibroblast. Western blot results revealed that p65 and IKKB were significantly less expressed in Chinese medicine group, while pIkappaBalpha and pIKKalphabeta expression were significantly increased. We have also found that in this group the expression of pAKT was evidently suppressed and expression of pERK significantly decreased. PCR results showed significantly decreased expression levels of IL-10 and 1IL-12b in Chinese medicine group, while the expression of IL 12a was increased. Our results suggest that Shuizhongcao Granule can suppress the proliferation of fibroblast and inhibit the activation of NF-kappaB and thus suppress inflammatory reactions, possibly involving the inhibited expression of phosphorylated AKT, rather than the canonical pathway. Furthermore, it can inhibit ERK pathway and reduce IL-10 and IL-12b gene expression while enhancing IL-12a expression. PMID- 26557147 TI - The Renal Protective Effect of Jiangya Tongluo Formula, through Regulation of Adrenomedullin and Angiotensin II, in Rats with Hypertensive Nephrosclerosis. AB - We investigated the effect of Jiangya Tongluo (JYTL) formula on renal function in rats with hypertensive nephrosclerosis. A total of 21 spontaneously hypertensive rats (SHRs) were randomized into 3 groups: valsartan (10 mg/kg/d valsartan), JYTL (14.2 g/kg/d JYTL), and a model group (5 mL/kg/d distilled water); Wistar Kyoto rats comprised the control group (n = 7, 5 mL/kg/d distilled water). Treatments were administered by gavage every day for 8 weeks. Blood pressure, 24-h urine protein, pathological changes in the kidney, serum creatinine, and blood urea nitrogen (BUN) levels were estimated. The contents of adrenomedullin (ADM) and angiotensin II (Ang II) in both the kidney and plasma were evaluated. JYTL lowered BP, 24-h urine protein, serum creatinine, and BUN. ADM content in kidneys increased and negatively correlated with BP, while Ang II decreased and negatively correlated with ADM, but there was no statistically significant difference of plasma ADM between the model and the treatment groups. Possibly, activated intrarenal renin-angiotensin system (RAS) plays an important role in hypertensive nephrosclerosis and the protective function of ADM via local paracrine. JYTL may upregulate endogenous ADM level in the kidneys and antagonize Ang II during vascular injury by dilating renal blood vessels. PMID- 26557148 TI - Mechanistic Study of the Phytocompound, 2- beta -D-Glucopyranosyloxy-1 hydroxytrideca-5,7,9,11-tetrayne in Human T-Cell Acute Lymphocytic Leukemia Cells by Using Combined Differential Proteomics and Bioinformatics Approaches. AB - Bidens pilosa, a medicinal herb worldwide, is rich in bioactive polyynes. In this study, by using high resolution 2-dimensional gel electrophoresis coupled with mass spectrometry analysis, as many as 2000 protein spots could be detected and those whose expression was specifically up- or downregulated in Jurkat T cells responsive to the treatment with 2-beta-D-glucopyranosyloxy-1-hydroxytrideca 5,7,9,11-tetrayne (GHTT) can be identified. GHTT treatment can upregulate thirteen proteins involved in signal transduction, detoxification, metabolism, energy pathways, and channel transport in Jurkat cells. Nine proteins, that is, thioredoxin-like proteins, BH3 interacting domain death agonist (BID protein involving apoptosis), methylcrotonoyl-CoA carboxylase beta chain, and NADH ubiquinone oxidoreductase, were downregulated in GHTT-treated Jurkat cells. Further, bioinformatics tool, Ingenuity software, was used to predict signaling pathways based on the data obtained from the differential proteomics approach. Two matched pathways, relevant to mitochondrial dysfunction and apoptosis, in Jurkat cells were inferred from the proteomics data. Biochemical analysis further verified both pathways involving GHTT in Jurkat cells. These findings do not merely prove the feasibility of combining proteomics and bioinformatics methods to identify cellular proteins as key players in response to the phytocompound in Jurkat cells but also establish the pathways of the proteins as the potential therapeutic targets of leukemia. PMID- 26557149 TI - Antiosteoporotic Effects of Huangqi Sanxian Decoction in Cultured Rat Osteoblasts by Proteomic Characterization of the Target and Mechanism. AB - Huangqi Sanxian decoction (HQSXD) is routinely used for the treatment of osteoporosis in the Chinese traditional healthcare system. However, the targets and mechanism underlying the effect of HQSXD on osteoporosis have not been documented. In the present study, seropharmacology and proteomic approaches (two dimensional gel electrophoresis combined with mass spectrometry) were used to investigate the effects and possible target proteins of HQSXD on osteoblast. We found that HQSXD-treated rat serum significantly enhanced osteoblast proliferation, differentiation, and mineralization. In HQSXD-S-treated osteoblasts, there were increases in the expression of N-formyl peptide receptor 2 and heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1 and reduction in the expression of alpha-spectrin, prohibitin, and transcription elongation factor B (SIII), polypeptide 1. The identified proteins are associated with cell proliferation, differentiation, signal transcription, and cell growth. These findings might provide valuable insights into the mechanism of antiosteoporotic effect affected by HQSXD treatment in osteoblasts. PMID- 26557146 TI - Proteomics in Traditional Chinese Medicine with an Emphasis on Alzheimer's Disease. AB - In recent years, there has been an increasing worldwide interest in traditional Chinese medicine (TCM). This increasing demand for TCM needs to be accompanied by a deeper understanding of the mechanisms of action of TCM-based therapy. However, TCM is often described as a concept of Chinese philosophy, which is incomprehensible for Western medical society, thereby creating a gap between TCM and Western medicine (WM). In order to meet this challenge, TCM research has applied proteomics technologies for exploring the mechanisms of action of TCM treatment. Proteomics enables TCM researchers to oversee various pathways that are affected by treatment, as well as the dynamics of their interactions with one another. This review discusses the utility of comparative proteomics to better understand how TCM treatment may be used as a complementary therapy for Alzheimer's disease (AD). Additionally, we review the data from comparative AD related TCM proteomics studies and establish the relevance of the data with available AD hypotheses, most notably regarding the ubiquitin proteasome system (UPS). PMID- 26557150 TI - Application of Herbal Medicines with Bitter Flavor and Cold Property on Treating Diabetes Mellitus. AB - Diabetes mellitus has been a global pandemic. Traditional Chinese Medicine has been used on diabetes mellitus for thousands of years and the modern Chinese medicine studies have found a curative effect of herbal medicine with bitter flavor and cold property on diabetes. This review will introduce the theory summary of flavor and property in TCM, argument basis, the evidences from clinical trails and animal experiments, the possible antidiabetic mechanisms, and advantages on lowering glucose of herbal medicines with bitter flavor and cold property and take rhizome, Chinese rhubarb, and Momordica charantia, the three herbal medicines with bitter flavor and cold property, as examples to illustrate the exact antidiabetic effect. It is hoped that this review can provide some ideas and inspiration for the treatment of diabetes with herbal medicine. PMID- 26557151 TI - Sense of Well-Being in Patients with Fibromyalgia: Aerobic Exercise Program in a Mature Forest-A Pilot Study. AB - Background and Objective. Most patients with fibromyalgia benefit from different forms of physical exercise. Studies show that exercise can help restore the body's neurochemical balance and that it triggers a positive emotional state. So, regular exercise can help reduce anxiety, stress, and depression. The aim of this study was to analyze the benefits of moderate aerobic exercise when walking in two types of forests, young and mature, and to assess anxiety, sleep, pain, and well-being in patients with fibromyalgia. Secondary objectives included assessing (i) whether there were differences in temperature, sound, and moisture, (ii) whether there was an improvement in emotional control, and (iii) whether there was an improvement in health (reduction in pain) and in physical and mental relaxation. Patients and Methods. A study involving walking through two types of forests (mature and young) was performed. A total of 30 patients were randomly assigned to two groups, mature and young forests. The participants were administered the following tests: the Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR) at baseline and the end-point of the study, the State Trait Anxiety Inventory (STAI) after each walk, and a series of questions regarding symptomatic evolution. Several physiological parameters were registered. Results. FIQR baseline and end-point scores indicated a significant decrease in the symptomatic subscale of the FIQ (SD = 21.7; z = -2.4; p = 0.041). The within-group analysis revealed that differences were significant with respect to days of intense pain, insomnia, and days of well-being only in the group assigned to the mature forest, not in the group assigned to the young forest. No differences were found with respect to anxiety. Conclusions. Although the main aim of this research was not achieved, as the results revealed no differences between the groups in the two forest types, authors could confirm that an aerobic exercise program consisting of walking through a mature forest can provide the subjective perception of having less days of pain and insomnia and more days of wellness, in patients with fibromyalgia. PMID- 26557152 TI - Qing Re Liang Xue Decoction Alleviates Hypercoagulability in Kawasaki Disease. AB - Objective. Kawasaki disease (KD) is a multisystemic autoimmune vasculitis. Intravenous immunoglobulin (IVIG) is the first-line treatment for KD. It is unclear whether traditional Chinese medicine (TCM) has an effect on KD. We aimed to observe the clinical efficacy of TCM on acute KD via serum interleukin-33 (IL 33) and tumor necrosis factor alpha (TNF-alpha) measurements. Methods. Thirty-one KD patients were treated with Qing Re Liang Xue decoction and Western medicine (integrative medicine treatment group), while 28 KD patients were treated with Western medicine only (Western medicine treatment group). Thirty patients were included in a febrile group and 28 healthy children were included in the control group. Clinical characteristics and laboratory findings were gathered and compared. Serum IL-33 and TNF-alpha levels were measured by multiplex Luminex assay. Results. The platelet count in the integrative medicine treatment group was significantly lower than that in the Western medicine treatment group. The integrative medicine group had a shorter fever duration and lower IL-33 and TNF alpha levels than those in the Western medicine group, but there were no significant differences between the two KD groups after treatment. Conclusion. Qing Re Liang Xue decoction improved the hypercoagulable state of KD patients. Potential myocardial protective effects require further research. PMID- 26557153 TI - RNAi2015 - Ten years of RNAi Oxford. AB - The tenth RNAi conference was held at St. Hilda's College Oxford on the 24-26 March 2015. The conference offered researchers from all over the world the chance to present, discuss and discover work pertaining to the field of RNAi. RNAi has become an essential technique in genomic research for functional validation as well as an exciting avenue to explore in therapeutic medicine. Emerging techniques such as CRISPR as well as improvements in efficiency of existing techniques and expansions in libraries have cemented the importance of RNAi at the cutting edge of research. Featured presentations and posters showcased recent research in the field ranging from RNA detection in bio fluids through to potential oligonucleotide therapies. PMID- 26557154 TI - Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data. AB - We studied the problem of mortality prediction in two datasets, the first composed of 23 septic shock patients and the second composed of 73 septic subjects selected from the public database MIMIC-II. For each patient we derived hemodynamic variables, laboratory results, and clinical information of the first 48 hours after shock onset and we performed univariate and multivariate analyses to predict mortality in the following 7 days. The results show interesting features that individually identify significant differences between survivors and nonsurvivors and features which gain importance only when considered together with the others in a multivariate regression model. This preliminary study on two small septic shock populations represents a novel contribution towards new personalized models for an integration of multiparameter patient information to improve critical care management of shock patients. PMID- 26557155 TI - Sleep as a window into early neural development: Shifts in sleep-dependent learning effects across early childhood. AB - Sleep is an important physiological state for the consolidation and generalization of new learning in children and adults. We review the literature on sleep-dependent memory consolidation and generalization in infants and preschool children and place the findings in the context of the development of the neural systems underlying memory (hippocampus and its connections to cortex). Based on the extended trajectory of hippocampal development, transitions in the nature of sleep-dependent learning are expected. The studies reviewed here show shifts in the nature of sleep-dependent learning across early childhood, with sleep facilitating generalization in infants but enhancing precise memory after 18-24 months of age. Future studies on sleep-dependent learning in infants and young children must take these transitions in early brain development into account. PMID- 26557156 TI - Impact of human papillomavirus on head and neck squamous cell cancers in Gabon. AB - Head and neck squamous cell cancers are among the most aggressive. Their incidence and mortality rates are relatively lower in Middle Africa than worldwide, but in Gabon, these rates tend to be 2-3 fold higher than in neighboring countries. The main risk factors are alcohol and tobacco consumption. However, in the last decades, there was cumulated evidence that human papillomaviruses were a significant risk factor, particularly for oropharyngeal squamous cell cancer. In Gabon, as elsewhere in Africa, assessment of these 3 risk factors need to be improved to determine their respective role in the development of head and neck squamous cell cancers. The potential differences in alcohol/tobacco consumption habits as well as in infectious ecology between developing and developed countries can make it difficult to transpose current data on this issue. Determining the respective role of alcohol/tobacco consumption and human papillomaviruses in the development of head and neck squamous cell cancers is crucial for the management of these cancers that could become a serious public health issue in Gabon. Human papillomaviruses are not only a risk factor but also a biomarker with promising clinical potential for the follow-up of head and neck squamous cell cancers potentially able to select an adequate treatment. Then, assessing the epidemiological impact of human papillomaviruses in Gabon and in all of Africa would prove useful for the clinical follow-up of head and neck squamous cell cancers, and would also provide essential data to plan a global prevention strategy against head and neck squamous cell cancers due to human papillomaviruses. PMID- 26557157 TI - De Novo ring chromosome 11 and non-reciprocal translocation of 11p15.3-pter to 21qter in a patient with congenital heart disease. AB - BACKGROUND: Ring chromosome 11[r (11)] is a rare chromosomal abnormality that forms when both arms of chromosome 11 break, and then reunite with each other. Once a ring chromosome forms, the distal ends of both arms of the chromosome are usually lost. CASE PRESENTATION: We reported a 12 years old girl patient with congenital heart disease and distinctive facial features. Cytogenetic and molecular analyses using standard G-banding, fluorescence in situ hybridization and Single nucleotide polymorphism array were performed to identify genetic causes in the patient. The patient carried r(11)(p15.3q24.1) and 11p15.3-pter non reciprocal translocation to 21qter, accompanied with 8.9 Mb deletion of 11q24.2q25. A literature review was performed to establish genotype-phenotype correlations of the r (11) and 11q terminal deletion syndrome. CONCLUSIONS: To the best of our knowledge, this is the first case of non-reciprocal translocation with a terminal deletion in r (11). These findings provide important information for genetic counseling for this family, and may improve our understanding of the genotype-phenotype correlation of ring chromosome 11 disorders. PMID- 26557158 TI - Analysis of survival in pediatric high-grade brainstem gliomas: A population based study. AB - BACKGROUND: The purpose of this study was to use the National Cancer Institutes' Surveillance, Epidemiology, and End Results (SEER) database to perform a large scale analysis of brainstem anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Use of the SEER database gave us a larger sample size of this rare tumor type, allowing for the analysis of the relationship between prognostic factors and survival. MATERIALS AND METHODS: We selected pediatric patients (<18 years old) from the SEER database with histologically confirmed diagnoses of primary high-grade gliomas (World Health Organization Grade III/IV) of the brainstem. In univariate and multivariate analysis, we analyzed the relationship between demographic (age, gender, race, diagnosis date), histologic (AA, GBM), and treatment (surgery, radiation) factors on survival. RESULTS: In our cohort of 124 patients, those with AA had a median survival of 13 months and those with GBM 9 months. Higher-grade tumors were associated with statistically significantly increased mortality (hazard ratio [HR]: 1.74, confidence intervals [CIs]: 1.17 2.60). Surgical intervention was associated with a significantly lower mortality, either alone (HR: 0.14, CI: 0.04-0.5) or in combination with radiation (HR: 0.35, CI: 0.15-0.82). Radiation therapy alone was significantly associated with decreased mortality within the first 9 months after diagnosis but not with overall mortality. No demographic characteristics were significantly associated with mortality. CONCLUSIONS: Outcome remains poor in the pediatric high-grade brainstem glioma population. Survival is correlated with lower-grade tumor histology, radiation therapy only in the first 9 months after diagnosis, and surgical resection. PMID- 26557159 TI - Novel mutation detection of fibroblast growth factor receptor 1 (FGFR1) gene, FGFR2IIIa, FGFR2IIIb, FGFR2IIIc, FGFR3, FGFR4 gene for craniosynostosis: A prospective study in Asian Indian patient. AB - BACKGROUND: Craniosynostosis (CS) syndrome is an autosomal dominant condition classically combining craniosynostosis and non-syndromic craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a larger number of cases can be attributed to mutations outside this region of the protein. AIMS: To find out the FGFR1, FGFR2, FGFR3 and FGFR4 gene in craniosynostosis syndrome. SETTINGS AND DESIGN: A hospital based prospective study. MATERIALS AND METHODS: Prospective analysis of clinical records of patients registered in CS clinic from December 2007 to January 2015 was done in patients between 4 months to 13 years of age. We have performed genetic findings in a three generation Indian family with Craniosynostosis syndrome. RESULTS: We report for the first time the clinical and genetic findings in a three generation Indian family with Craniosynostosis syndrome caused by a heterozygous missense mutation, Thr 392 Thr and ser 311 try, located in the IgII domain of FGFR2. FGFR 3 and 4 gene basis syndrome was eponymously named. Genetic analysis demonstrated that 51/56 families to be unrelated. In FGFR3 gene 10/TM location of 1172 the nucleotide changes C>A, Ala 391 Glu 19/56 and Exon-19, 5q35.2 at conserved linker region the changes occurred pro 246 Arg in 25/56 families. CONCLUSIONS: Independent genetic origins, but phenotypic similarities in the 51 families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation. PMID- 26557160 TI - Pediatric intramedullary spinal cord lesions: Pathological spectrum and outcome of surgery. AB - BACKGROUND: Pediatric intramedullary spinal cord lesions are not only rare but also different from adults in a number of aspects. We aimed to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome of treatment. MATERIALS AND METHODS: Thirty-one consecutive children (aged 1-18 years, mean 11.1 years, male: female = 1.8:1) with pathologically proven intramedullary spinal cord lesions treated at our center were studied. Clinico radiological, histopathological, operative, and outcome data were reviewed retrospectively. The functional status was assessed using the modified McCormick grading system. RESULTS: Gross total tumor excision was performed in 19 patients (61.3%), subtotal in 9 patients (29%), partial excision was performed in 2 (6.5%) patient, and only biopsy was performed in 1 patient (6.5%). There was one peroperative death, 2 patients died at follow-up. Complications included wound related complications (n = 4), transient deterioration in the motor power, and respiratory complication requiring a tracheostomy. Six patients showed recurrence at a mean follow-up of 16.4 months. Developmental tumors, high-grade ependymomas, and incompletely excised grade 2 ependymomas showed a tendency to recur. CONCLUSIONS: Children constituted nearly 1/5(th) (17.4%) of intramedullary spinal cord tumors. Astrocytomas and ependymomas taken together constituted the most common intramedullary spinal lesions in children; however, developmental tumors predominated in the first decade. Children usually presented in good functional grades preoperatively and maintained good grades after surgery. Functional outcome was dependent on the preoperative neurological status and histopathology of the lesions. PMID- 26557161 TI - Parameters of metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. AB - OBJECTIVES: The prevalence of obesity is rapidly increasing among Indian children, who, in general, are more prone to develop metabolic complications at an early age. Valproate and phenytoin are commonly used antiepileptic drugs in children. This study aimed to assess the parameters of the metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. METHODS: This cross-sectional study recruited children from the Pediatric Epilepsy Clinic, Department of Pediatrics, Kalawati Saran Children Hospital, New Delhi from March 2012 to September 2012. All consecutive children diagnosed with epilepsy as per International League Against Epilepsy definition aged 3-18 years on valproate or phenytoin monotherapy for at least 6 months were enrolled at a tertiary care children's hospital in Northern India. After clinical and anthropometric evaluation (including body mass index [BMI] and waist circumference), the blood samples were analyzed for fasting serum glucose, total cholesterol, high-density lipoprotein-cholesterol, and serum triglyceride. RESULTS: Children with BMI >95(th) centile and waist circumference >90(th) centile were not significantly different among children on valproate and phenytoin monotherapy. Children on valproate had significantly higher mean serum triglyceride (96.9 mg/dL vs. 77.6 mg/dL; P < 0.001) and total cholesterol (148.3 mg/dL vs. 132.8 mg/dL; P = 0.002) levels as compared to children on phenytoin monotherapy. CONCLUSIONS: The lipid abnormalities may be observed in children on valproate or phenytoin therapy and may warrant periodic screening. PMID- 26557162 TI - Pattern, etiological factors and determinants of mortality among sick newborns with seizures in Ilesa, Nigeria. AB - BACKGROUND: Neonatal seizures contribute significantly to newborn morbidity and mortality particularly in developing countries including Nigeria. Unfortunately the countries with high incidence of neonatal seizures often lack the facilities to adequately diagnose, monitor and prognosticate the condition. OBJECTIVE: We set out to determine the factors at presentation that predict death among babies admitted with clinically identifiable seizures. METHODS: We prospectively observed consecutive neonatal admissions over a nine month period at the Wesley Guild Hospital, Ilesa, Nigeria. Babies with seizures were identified based on clinical observation. Perinatal history, examination and laboratory findings were compared between babies with seizures who survived and those that died. Multivariate regression analysis was used to determine the predictors of mortality. RESULTS: Over a nine month study period, a total of 340 babies were recruited out of which 55 (16.7 percent) had clinically identifiable seizures. Fifteen (27.3 percent) of the 55 babies with clinically identifiable seizures died; while 20 (7.0 percent) of the 285 babies without seizures died. Clinically identifiable neonatal seizures contributed to 42.9 percent of the overall mortality in the neonatal unit during the study period. The risk factors for mortality among the babies with seizures were clinical seizures in the first 24 hours of life, birth asphyxia co-existing with hyponatraemia and presence of cerebral oedema (P < 0.05). The independent determinant of mortality among babies with clinical seizures was cerebral oedema (OR = 4.025; 95% CI 1.342-26.956; P = 0.019). CONCLUSION: We conclude that clinically identifiable neonatal seizures contribute significantly to neonatal mortality and presentation within 24 hours of delivery, birth asphyxia and cerebral oedema increased the risk of death in babies with seizures. PMID- 26557163 TI - Symmetrical central tegmental tract hyperintensities on magnetic resonance imaging. PMID- 26557164 TI - Diastematomyelia with hemimyelomeningocele: An exceptional and complex spinal dysraphism. AB - Variations in split cord malformation (SCM) have been described earlier. However, a true hemimyelomeningocele (HMM) as only congenital malformation is extremely rare and is reported infrequently in published literature. We are reporting the case of a 3-month-old girl child who presented with a swelling on the lower back since birth. Magnetic resonance imaging revealed a type 1 SCM with right hemicord forming a HMM. Precise diagnosis and thorough anatomical detail of dysraphism is essential for optimal, individualized neurosurgical management. PMID- 26557165 TI - Acute onset of postoperative syringohydromyelia. AB - Syringohydromyelia is a frequent finding in cases of tethered cord syndrome. The classical teaching is that the development and progression of a syrinx is a chronic process. We present a case report of an acute onset syringomyelia in an infant, who underwent an excision of a lumbosacral transitional lipoma and detethering of the cord. Immediately after recovery, the infant was found to have flaccid paraplegia. An emergency magnetic resonance imaging revealed a large acute onset syringomyelia for which he underwent an emergency midline myelotomy and release of fluid from the syrinx. Though the eventual recovery was good, this made us re-visit our understanding of the concept of syringohydromyelia. The case details and a plausible hypothesis for the rapid development of the syrinx are presented. PMID- 26557166 TI - Middle interhemispheric variant of holoprosencephaly: A rare midline malformation. AB - Middle interhemispheric variant (MIH) of holoprosencephaly (HPE) or syntelencephaly is a rare variant of HPE characterized by abnormal midline union of the posterior frontal and parietal lobes with variable fusion of thalami. It varies from classic HPE in embryopathogenesis, severity of fusion of brain structures, associated craniofacial anomalies and clinical presentation. We report a case of MIH in a 5-year-old girl, who presented with severe developmental delay and discuss the features differentiating it from other more common forms of HPE. PMID- 26557167 TI - Rare case of anterior fontanelle epidermoid/dermoid. AB - Anterior fontanelle cysts are rare in occurrence in the area of anterior fontanelle. Most of them are dermoid cysts. Epidermoid cysts are even rarer to be seen. Authors are reporting a rare case of epidermoid cyst located in anterior fontanelle along with two cases of dermoid in this area. Magnetic resonance imaging revealed that a cystic swelling was present in the anterior fontanelle area. Few cases have been reported in the literature. Present case of epidermoid is analysed and available literature is reviewed. PMID- 26557168 TI - Posterior fossa infected dermoid with congenital heart disease: A novel hypothesis of an unusual association. AB - Intracranial dermoid cysts commonly present as a discharging sinus, local swelling, mass lesion, or abscess formation. These can sometimes be found in association with congenital anomalies. The author presents two original cases of infected posterior fossa dermoid associated with congenital heart diseases (CHDs) that is very rare. The embryologic basis for this unique occurrence is reviewed, and a new hypothesis proposed. Two infants with CHD presented with infected midline posterior fossa dermoid. Excision of the dermoid cyst with the sinus tract was performed. Postoperative period was uneventful. Both the infants had undergone surgery for congenial heart disease a few months prior to the present clinical presentation with uneventful recovery. Infected posterior fossa dermoid cyst without a discharging sinus should prompt a thorough examination to detect CHD. Early diagnosis and timely management results in better outcome. PMID- 26557169 TI - A case of mitochondrial cytopathy with exertion induced dystonia. AB - Paroxysmal dystonias are a group of relatively benign hyperkinetic childhood movement disorders of varied etiology. Mitochondrial diseases are well known to produce persistent dystonias as sequelae, but paroxysmal exertion induced dystonia has been reported in only one case to the best of our knowledge. Two siblings born to consanguineous parents presented with early-onset exertion induced dystonia, which was unresponsive to diphenylhydantoin and carbamazepine. A trial with valproate in one of the siblings turned fatal within 24 h. Based on this clue, the second child was investigated and found to suffer from complex I deficiency with a paternally inherited dominant nuclear DNA mutation, which is responsive to the mitochondrial cocktail. Exertion induced dystonia can be a rare manifestation of complex I deficiency. PMID- 26557170 TI - Neurobehavioral phenotype in cyclin-dependent kinase-like 5 syndrome: Case report and review of literature. AB - The phenotype of cyclin-dependent kinase-like 5 (CDKL5) syndrome includes Rett syndrome variant with early onset seizures, early onset epileptic encephalopathy; and severe developmental delay. Autistic features have often been reported in literature, but detailed reports of the behavior of these individuals are lacking. We describe the clinical picture of a girl aged 15 years 9 months affected by CDKL5 syndrome, with special attention to the neurobehavioral phenotype. The evaluation showed, apart from a profound intellectual disability, the presence of atypical features of behavior, mainly in relating to people, in imitation, and in verbal and nonverbal communication, thus justifying the diagnosis of comorbid autism spectrum disorder. A formal assessment of the behavior, through appropriate tools, is necessary to choose the most appropriate rehabilitative intervention and to characterize in more detail the CDKL5 syndrome phenotype. We propose a testing protocol for the neurobehavioral assessment of these patients. PMID- 26557171 TI - Linear undisplaced fracture of temporoparietal bone acting as spontaneous early decompressive craniotomy in a neonate. AB - Decompressive craniotomy (DC) is used to treat intracranial hypertension associated with traumatic brain injury. Early DC is associated with better outcomes. We present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture. This acted as a spontaneous DC causing bony segment to separate due to which the edematous brain could be accommodated. Despite the presence of a large contusion, the child was neurologically intact and medically managed. The neonate presented with a posttraumatic leptomeningeal cyst 2 months later, which had to be repaired surgically. We discuss how a linear undisplaced fracture acts as spontaneous DC and the role of early DC in improving outcomes. PMID- 26557172 TI - Split calvarial fracture: A rare cause of hypovolemic shock in an infant. AB - The present report describes a rare type split fracture of a calvarial bone, causing hypovolemic shock in an infant. The infant responded well to resuscitative measures. The authors discuss the possible mechanisms behind such a calvarial fracture. PMID- 26557174 TI - Bilateral occipital extradural hematoma in a child. AB - Extradural hematoma (EDH) occurs in approximately 2% of all patients with head injuries. Bilateral EDHs account for 2-10% of all acute EDHs in adults but are exceedingly rare in children. Posterior fossa EDHs occurs in 5% of all cases of EDHs. EDHs in children are more frequently venous (from tears of a dural sinus or diploic veins) and consequently have a better prognosis than EDHs in adults. Once the diagnosis of BEH is confirmed, urgent surgical treatment should be considered. We are reporting such rare form of injury as bilateral occipital EDH with supratentorial extension in 12 years child following road traffic accident. PMID- 26557173 TI - Intracranial extradural hematoma: Spontaneous rapid decompression - not resolution. AB - The surgical option to evacuate an intracranial extradural hematoma (EDH) was postponed in a 2-year-old female child who appeared fully alert and active after a brief spell of unconsciousness following a fall from height. The child was received, with a swelling on and around the right parietal eminence, by the emergency staff just half an hour after the time of injury. The immediate X-ray skull and first computed tomography (CT) scan head showed a parietal bone fracture, EDH, and cephalhematoma. However, follow-up CT scan head after about 41/2 h revealed the dramatic absence of EDH but increased size and bogginess of cephalhematoma. The EDH had transported into subgaleal space resulting in a decompression of intracranial compartment in <5 h, thereby preventing surgical intervention but necessitating monitoring, though there was no back flow intracranially. PMID- 26557175 TI - Rare association of thin corpus callosum with infantile tremor syndrome in a 5.5 month-old infant. AB - Infantile tremor syndrome (ITS) is a clinical disorder characterized by coarse tremors, anemia and regression of motor and mental milestones, presenting in malnourished children aged between 5 months and 3 years. Few reports of neuroimaging abnormalities in children with ITS are present. The most common finding of neuroimaging in ITS is cerebral atrophy with ex-vacuo enlargement of ventricles and subarachnoid space, some recent reports also showed pontine myelinolysis and cerebral hyperintensities. We did not find any report of thin corpus callosum associated with ITS in the literature. PMID- 26557176 TI - Childhood-onset (Juvenile) Huntington's disease: A rare case report. AB - Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions. PMID- 26557177 TI - A rare cause of acute flaccid paralysis: Human coronaviruses. AB - Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co infection by the real-time polymerase chain reaction, has been reported for the first time. PMID- 26557178 TI - Neonatal brain abscess: An atypical presentation. AB - Brain abscesses occur as an uncommon complication of bacterial meningitis in the neonatal period. A 34 weeks preterm at-risk neonate presented with abnormal breathing pattern and inability to maintain the oxygen saturation in room air. Magnetic resonance imaging (MRI) study revealed intra-parenchymal brain abscesses in the left basal ganglion and bilateral fronto-parietal regions. Intravenous piperacillin - tazobactam was commenced and continued for 6 weeks in Neonatal Intensive Care Unit. No surgical intervention was required. The patient responded to the medical management and was discharged after the documentation of radiological clearance in repeat MRI study. No complications were recorded. An appropriate neuro-developmental outcome was observed on follow-up. Brain abscesses may not be preceded by meningitis in all neonates. A strong clinical suspicion is required for the diagnosis especially in cases with atypical presentation. PMID- 26557179 TI - Bilateral symmetrical infratentorial subdural empyema: Delay proves detrimental. AB - Authors report a case of infratentorial subdural empyema, a rare complication of neglected otitis media in a child. PMID- 26557180 TI - Fatal cerebellar hemorrhage as an initial presentation of medulloblastoma in a child. AB - Children with medulloblastomas most commonly present with signs and symptoms of elevated intracranial pressure due to obstructive hydrocephalus, especially headaches and vomiting. However, some pediatric patients present with sudden neurological deterioration due to intracerebellar hemorrhage associated with medulloblastoma, although very few reports exist that document this phenomenon. An 8-year-old girl was admitted to our emergency department who presented with sudden loss of consciousness, vomiting, and bradycardia. The neuroradiological evaluation revealed a hemorrhagic mass lesion in the posterior fossa. Urgent evacuation of the hematoma was performed. The postoperative course was uneventful, and the postoperative histopathological examination revealed the lesion to be a medulloblastoma. This report presents an unusual case of a medulloblastoma presenting with fatal intracranial hemorrhage in a child. The clinical features and intraoperative and pathologic findings of the case are discussed. PMID- 26557181 TI - Giant pediatric glioblastoma multiforme causing primary calvarial erosion and sutural diastasis presenting with enlarged head. AB - Authors report a rare case of supratentorial glioblastoma multiforme in a 13-year old boy, who had headache, vomiting and left sided hemiparesis for last 6 months. On evaluation by primary physician he was labeled as hydrocephalus in view of enlarged head with papilledema on fundoscopic evaluation and no imaging was carried out. On current admission, magnetic resonance imaging brain revealed a large heterogeneous mass lesion involving right frontoparietal region associated with massive perilesional edema causing significant mass effect. He underwent right fronto-temporal craniotomy and intraoperatively erosion of parietal bone was observed, unassociated with any extradural deposit of tumor. After surgery, he noticed improvement in headache along with hemiparesis. Primary calvarial erosion in glioblastoma is extremely rare, and there is paucity of literature as evident from the few case reports reported previously and all occurred in elderly, so current case is the first pediatric case having primary calvarial erosion. Management of such case and pertinent literature is briefly discussed. PMID- 26557182 TI - Magnetic resonance imaging depiction of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis: Report of two cases. AB - Acquired Dyke-Davidoff-Masson syndrome, also known as hemispheric atrophy, is characterized by loss of volume of one cerebral hemisphere from an insult in early life. Crossed cerebellar diaschisis refers to dysfunction/atrophy of cerebellar hemisphere which is secondary to contralateral supratentorial insult. We describe magnetic resonance imaging findings in two cases of acquired Dyke Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis. PMID- 26557183 TI - Dry beriberi preceded Wernicke's encephalopathy: Thiamine deficiency after laparoscopic sleeve gastrectomy. AB - In recent times, pediatric obesity has become widely prevalent. If first-line treatment with lifestyle modification fails, bariatric surgery may be indicated for severely obese patients. Many patients now travel abroad to get these surgeries done. Some of these patients receive inadequate postoperative care. We described a morbidly obese 17-year-old girl who had a laparoscopic sleeve gastrectomy procedure for weight loss. Due to severe nausea, she stopped her multivitamin supplementation. Within a few weeks, she developed symptoms of dry beriberi was soon followed by classic symptoms of Wernicke's encephalopathy. The prompt diagnosis was made with confirmation from serum thiamine level and brain magnetic resonance imaging. Thiamine supplementation reversed ophthalmological symptoms promptly. However, the patient needed inpatient rehabilitation for neuropathy. This case describes that thiamine deficiency can occur after restrictive bariatric surgery, despite lower risk of malnutrition in the absence of intestinal bypass procedure. This report highlights that in the presence of risk factors: dietary noncompliance, inadequate follow-up, and severe nausea with and without vomiting can precipitate the development of Wernicke's encephalopathy, even after restrictive surgery. Physicians may increasingly encounter thiamine and other nutrient deficiencies in increasing numbers due to increasing prevalence of obesity disorders and availability of bariatric surgeries. This report also emphasized the importance of identifying vague sensory symptoms in thiamine deficiency. PMID- 26557185 TI - Effects of Supplementation with Neptune Krill Oil (Euphasia Superba) on Selected Redox Parameters and Pro-Inflammatory Markers in Athletes during Exhaustive Exercise. PMID- 26557184 TI - Examining Smoking Dependence Motives among African American Light Smokers. AB - INTRODUCTION: Despite smoking fewer cigarettes per day, African American smokers have greater difficulty quitting compared to Caucasian smokers. Further elucidating the impact of smoking motivations on smoking behavior would contribute to understanding the factors that maintain smoking. AIMS: This study examined the factor structure of a brief assessment examining smoking dependence motives among a sample of African American light smokers. METHODS: Data from a double-blind, placebo-controlled randomized smoking cessation trial involving 540 participants. Results were analyzed using an exploratory factor analysis (EFA) and a randomly split EFA. RESULTS/FINDINGS: Findings from the initial EFA analysis produced an 8-factor model, explaining 69% of the variation in responses. The overall Measure of Sampling Adequacy (MSA) was 0.88 with item level MSA ranging 0.68-0.94 across the 30 items. Results from the randomly split EFA replicated the findings of the original EFA; with the exception of the item "I smoke within the first 30 minutes of awakening in the morning". CONCLUSIONS: These findings support the hypothesis of a multidimensional approach to conceptualizing nicotine dependence, and provide information regarding characteristics of nicotine dependence in African American light smokers which may be helpful in identifying targets for cessation treatment in this population of smokers. PMID- 26557186 TI - Modelling of Muscle Force Distributions During Barefoot and Shod Running. AB - Research interest in barefoot running has expanded considerably in recent years, based around the notion that running without shoes is associated with a reduced incidence of chronic injuries. The aim of the current investigation was to examine the differences in the forces produced by different skeletal muscles during barefoot and shod running. Fifteen male participants ran at 4.0 m.s-1 (+/- 5%). Kinematics were measured using an eight camera motion analysis system alongside ground reaction force parameters. Differences in sagittal plane kinematics and muscle forces between footwear conditions were examined using repeated measures or Freidman's ANOVA. The kinematic analysis showed that the shod condition was associated with significantly more hip flexion, whilst barefoot running was linked with significantly more flexion at the knee and plantarflexion at the ankle. The examination of muscle kinetics indicated that peak forces from Rectus femoris, Vastus medialis, Vastus lateralis, Tibialis anterior were significantly larger in the shod condition whereas Gastrocnemius forces were significantly larger during barefoot running. These observations provide further insight into the mechanical alterations that runners make when running without shoes. Such findings may also deliver important information to runners regarding their susceptibility to chronic injuries in different footwear conditions. PMID- 26557187 TI - Certain Actions from the Functional Movement Screen Do Not Provide an Indication of Dynamic Stability. AB - Dynamic stability is an essential physical component for team sport athletes. Certain Functional Movement Screen (FMS) exercises (deep squat; left- and right leg hurdle step; left- and right-leg in-line lunge [ILL]; left- and right-leg active straight-leg raise; and trunk stability push-up [TSPU]) have been suggested as providing an indication of dynamic stability. No research has investigated relationships between these screens and an established test of dynamic stability such as the modified Star Excursion Balance Test (mSEBT), which measures lower-limb reach distance in posteromedial, medial, and anteromedial directions, in team sport athletes. Forty-one male and female team sport athletes completed the screens and the mSEBT. Participants were split into high-, intermediate-, and low-performing groups according to the mean of the excursions when both the left and right legs were used for the mSEBT stance. Any between group differences in the screens and mSEBT were determined via a one-way analysis of variance with Bonferroni post hoc adjustment (p < 0.05). Data was pooled for a correlation analysis (p < 0.05). There were no between-group differences in any of the screens, and only two positive correlations between the screens and the mSEBT (TSPU and right stance leg posteromedial excursion, r = 0.37; left-leg ILL and left stance leg posteromedial excursion, r = 0.46). The mSEBT clearly indicated participants with different dynamic stability capabilities. In contrast to the mSEBT, the selected FMS exercises investigated in this study have a limited capacity to identify dynamic stability in team sport athletes. PMID- 26557188 TI - Higher Neuromuscular Manifestations of Fatigue in Dynamic than Isometric Pull-Up Tasks in Rock Climbers. AB - Neuromuscular assessment of rock climbers has been mainly focused on forearm muscles in the literature. We aimed to extend the body of knowledge investigating on two other upper limb muscles during sport-specific activities in nine male rock climbers. We assessed neuromuscular manifestations of fatigue recording surface electromyographic signals from brachioradialis and teres major muscles, using multi-channel electrode arrays. Participants performed two tasks until volitional exhaustion: a sequence of dynamic pull-ups and an isometric contraction sustaining the body at half-way of a pull-up (with the elbows flexed at 90 degrees ). The tasks were performed in randomized order with 10 minutes of rest in between. The normalized rate of change of muscle fiber conduction velocity was calculated as the index of fatigue. The time-to-task failure was significantly shorter in the dynamic (31 +/-10 s) than isometric contraction (59 +/-19 s). The rate of decrease of muscle fiber conduction velocity was found steeper in the dynamic than isometric task both in brachioradialis (isometric: 0.2 +/-0.1%/s; dynamic: -1.2 +/-0.6%/s) and teres major muscles (isometric: 0.4+/-0.3%/s; dynamic: -1.8+/-0.7%/s). The main finding was that a sequence of dynamic pull-ups lead to higher fatigue than sustaining the body weight in an isometric condition at half-way of a pull-up. Furthermore, we confirmed the possibility to properly record physiological CV estimates from two muscles, which had never been studied before in rock climbing, in highly dynamic contractions. PMID- 26557189 TI - Comparison of Lower Limb Segments Kinematics in a Taekwondo Kick. An Approach to the Proximal to Distal Motion. AB - In taekwondo, there is a lack of consensus about how the kick sequence occurs. The aim of this study was to analyse the peak velocity (resultant and value in each plane) of lower limb segments (thigh, shank and foot), and the time to reach this peak velocity in the kicking lower limb during the execution of the roundhouse kick technique. Ten experienced taekwondo athletes (five males and five females; mean age of 25.3 +/-5.1 years; mean experience of 12.9 +/-5.3 years) participated voluntarily in this study performing consecutive kicking trials to a target located at their sternum height. Measurements for the kinematic analysis were performed using two 3D force plates and an eight camera motion capture system. The results showed that the proximal segment reached a lower peak velocity (resultant and in each plane) than distal segments (except the peak velocity in the frontal plane where the thigh and shank presented similar values), with the distal segment taking the longest to reach this peak velocity (p < 0.01). Also, at the instant every segment reached the peak velocity, the velocity of the distal segment was higher than the proximal one (p < 0.01). It provides evidence about the sequential movement of the kicking lower limb segments. In conclusion, during the roundhouse kick in taekwondo inter segment motion seems to be based on a proximo-distal pattern. PMID- 26557190 TI - Reliability Analysis of Traditional and Ballistic Bench Press Exercises at Different Loads. AB - The purpose of this study was to determine test-retest reliability for peak barbell velocity (Vpeak) during the bench press (BP) and bench press throw (BPT) exercises for loads corresponding to 20-70% of one-repetition maximum (1RM). Thirty physically active collegiate men conducted four evaluations after a preliminary BP 1RM determination (1RM.bw-1 = 1.02 +/- 0.16 kg.kg-1). In counterbalanced order, participants performed two sessions of the BP in one week and two sessions of the BPT in another week. Recovery time between sessions within the same week was 48 hours and recovery time between sessions of different weeks was 120 hours. On each day of evaluation the individual load-velocity relationship at each tenth percentile (20-70% of 1RM) in a Smith machine for the BP or BPT was determined. Participants performed three attempts per load, but only the best repetition (highest Vpeak), registered by a linear position transducer, was analysed. The BPT resulted in a significantly lower coefficient of variation (CV) for the whole load-velocity relationship, compared to the BP (2.48% vs. 3.22%; p = 0.040). Test-retest intraclass correlation coefficients (ICCs) ranged from r = 0.94-0.85 for the BPT and r = 0.91-0.71 for the BP (p < 0.001). The reduction in the biological within-subject variation in BPT exercise could be promoted by the braking phase that obligatorily occurs during a BP executed with light or moderate loads. Therefore, we recommend the BPT exercise for a most accurate assessment of upper-body velocity. PMID- 26557191 TI - Comparisons of a Multi-Frequency Bioelectrical Impedance Analysis to the Dual Energy X-Ray Absorptiometry Scan in Healthy Young Adults Depending on their Physical Activity Level. AB - This study aimed at comparing BIA and DXA results in assessing body composition in young adults depending on their physical activity level. Eighty healthy 19-30 years old subjects were enrolled and their body composition (Fat Mass and Fat Free Mass) was assessed by dual-energy X-ray absorptiometry (DXA) and by a newly developed Bioelectrical Impedance Analyzer (BIA - Tanita MC780). A seven-day physical activity level was assessed using a 3-axial accelerometer. DXA-FM% and BIA-FM% were correlated (p<0.001; r= 0.852; ICC [IC95%]: 0.84 [0.75 - 0.90]; concordance coefficient: 0.844). DXA-FFM and BIA FFM were correlated (p<0.001; r=0.976; ICC [IC95%]: 0.95 [0.93 - 0.97], concordance coefficient: 0.955). DXA and BIA measurements of FM% and FFM were highly correlated in both boys and girls regardless of the physical activity level. Compared with DXA scans, newly developed bioelectrical impedance analyzers provide satisfactory fat mass and lean mass measures in healthy young women and men, despite their physical activity level. PMID- 26557192 TI - Acute Exercise and Oxidative Stress: CrossFit(TM) vs. Treadmill Bout. AB - CrossFit(TM), a popular high-intensity training modality, has been the subject of scrutiny, with concerns of elevated risk of injury and health. Despite these concerns empirical evidence regarding physiologic stresses including acute oxidative stress is lacking. Therefore, the purpose of this investigation was to examine the acute redox response to a CrossFit(TM) bout. Furthermore, these findings were compared to a high-intensity treadmill bout as a point of reference. Ten males 26.4 +/- 2.7 yrs having three or more months of CrossFit(TM) experience participated in the present study. Blood plasma was collected at four time points: Pre-exercise (PRE), immediately-post-exercise (IPE), 1 hr-post (1 HP) and 2 hr-post (2-HP), to examine oxidative damage and antioxidant capacity. Regarding plasma oxidative damage, CrossFit(TM) and Treadmill elicited a time dependent increase of lipid peroxides 1-HP (CrossFit(TM)=+143%, Treadmill=+115%) and 2-HP (CrossFit(TM)=+256%, Treadmill+167%). Protein Carbonyls were increased IPE in CF only (+5%), while a time-dependent decrease occurred 1-HP (CrossFit(TM)=-16%, Treadmill=-8%) and 2-HP (CF=-16%, TM=-1%) compared to IPE. Regarding antioxidant capacity, Ferric Reducing Antioxidant Power also demonstrated a time-dependent increase within CrossFit(TM) and Treadmill: IPE (CrossFit(TM)=+25%, Treadmill=+17%), 1-HP (CrossFit(TM)=+26%, Treadmill=+4.8%), 2 HP (CrossFit(TM)=+20%, Treadmill=+12%). Total Enzymatic Antioxidant Capacity showed a time-dependent decrease in IPE (CrossFit(TM)=-10%, Treadmill=-12%), 1-HP (CrossFit(TM)=-12%, Treadmill=-6%), 2-HP (CrossFit(TM)=-7%, Treadmill=-11%). No trial-dependent differences were observed in any biomarker of oxidative stress. The CrossFit(TM) bout elicited an acute blood oxidative stress response comparable to a traditional bout of high-intensity treadmill running. Results also confirm that exercise intensity and the time course of exercise recovery influence oxidative responses. PMID- 26557193 TI - Can height categories replace weight categories in striking martial arts competitions? A pilot study. AB - In most combat sports and martial arts, athletes compete within weight categories. Disordered eating behaviors and intentional pre-competition rapid weight loss are commonly seen in this population, attributed to weight categorization. We examined if height categories can be used as an alternative to weight categories for competition, in order to protect the health of athletes. Height and weight of 169 child and adolescent competitive karate athletes were measured. Participants were divided into eleven hypothetical weight categories of 5 kg increments, and eleven hypothetical height categories of 5 cm increments. We calculated the coefficient of variation of height and weight by each division method. We also calculated how many participants fit into corresponding categories of both height and weight, and how many would shift a category if divided by height. There was a high correlation between height and weight (r = 0.91, p<0.001). The mean range of heights seen within current weight categories was reduced by 83% when participants were divided by height. When allocating athletes by height categories, 74% of athletes would shift up or down one weight category at most, compared with the current categorization method. We conclude that dividing young karate athletes by height categories significantly reduced the range of heights of competitors within the category. Such categorization would not cause athletes to compete against much heavier opponents in most cases. Using height categories as a means to reduce eating disorders in combat sports should be further examined. PMID- 26557194 TI - Does the GNB3 C825T Polymorphism Influence Swimming Performance in Competitive Swimmers? AB - Single nucleotide polymorphism C825T located within the GNB3 gene has been proposed in the literature as the performance enhancing polymorphism in highly trained athletes. Therefore, the aim of the present study was to verify the hypothesis assuming an association between the C825T polymorphic site and performance of competitive swimmers. The frequencies of C/T alleles and distribution of CC, CT and TT genotypes of the C825T GNB3 polymorphism were compared between athletes and nonathletic controls as well as between sprint and endurance swimmers. Genomic DNA was extracted from 197 competitive swimmers (50 long distance swimmers (LDS) and 147 short distance swimmers (SDS)) and 379 sedentary volunteers. The allele frequencies and genotype distribution of the C825T polymorphic site were not significantly different when LDS and SDS were compared to sedentary controls. Gender-specific analysis did not reveal any significant differences in allele and genotype distribution, neither between female controls and female swimmers nor between male controls and male swimmers. No significant differences in allele frequencies and genotype distribution were observed when LDS and SDS as well as groups of swimmers stratified by gender were compared. The results of this study do not support the hypothesis that the C825T polymorphism of the GNB3 gene is associated with swimming performance in competitive swimmers. PMID- 26557195 TI - Iron Metabolism in Field Hockey Players During an Annual Training Cycle. AB - Post-physical training changes in iron metabolism in the human body often occur. To fully describe these processes, fifteen male Polish National Team field hockey players (age 27.7 +/- 5.2 years, body mass 72.8 +/- 7.6 kg and body height 177.1 +/- 5.7 cm) were examined in three phases of an annual training cycle: preparatory (T1), competitive (T2) and transition (T3). To assess aerobic fitness, maximal oxygen uptake (VO2max) was evaluated. Based on the iron concentration, the changes in total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and other selected haematological indicators (haemoglobin, erythrocytes, mean corpuscular haemoglobin - MCH) in iron metabolism were estimated. The average values of maximum oxygen uptake increased from 54.97 +/- 3.62 ml.kg(-1).min(-1) in T1 to 59.93 +/- 3.55 ml.kg(-1).min(-1) in T2 (p<0.05) and then decreased to 56.21 +/- 4.56 ml.kg(-1).min(-1) in T3 (p<0.05). No statistically significant changes in the erythrocyte count were noted. The MCH and haemoglobin concentration decreased between T1 and T2. The maximal exercise test caused a significant (p<0.05) increase in the plasma iron concentration during the competition and transition phases. Progressive but non significant increases in resting iron concentration, TIBC and UIBC in the analysed annual training cycle were noted. To show global changes in iron metabolism in the human body, it is necessary to determine additional variables, i.e. UIBC, TIBC, haemoglobin, MCH or the erythrocyte count. The direction of changes in iron metabolism depends on both the duration and intensity of the physical activity and the fitness level of the subjects. Dietary intake of iron increases the level of this trace element and prevents anaemia associated with training overloads. PMID- 26557196 TI - Effect of a Six-Week Preparation Period on Acute Physiological Responses to a Simulated Combat in Young National-Level Taekwondo Athletes. AB - The aim of this study was to examine changes in physical attributes, physiological characteristics and responses that occurred in a simulated combat during a six-week preparatory period in young taekwondo athletes. Seven athletes (age 12.17 +/- 1.11 years) were examined before (pre-intervention) and after (post-intervention) a preparatory period for physical fitness and physiological responses to a 2*90 s simulated bout with a 30 s rest period. The heart rate (HR) was monitored during the simulated combat, and handgrip muscle strength (HMS) along with the countermovement jump (CMJ) were recorded before and after the combat. When compared with pre-intervention values, in post-intervention we observed a decrease in body mass, body fat percentage, and the HR at rest and during recovery after a 3 min step test, and an increase in maximal velocity of the cycle ergometer force-velocity test, the CMJ and mean power during the 30 s continuous jumping test (p<0.05). Furthermore, HR responses to a simulated combat were lower in the post-intervention session (p<0.05). CMJ values increased after the bout in both pre and post-intervention, with higher absolute values in the latter case (p<0.05), whereas there was no difference in HMS. Based on these findings, it can be concluded that the acute physiological responses to a simulated taekwondo combat vary during a season, which might be explained by changes in physical fitness. PMID- 26557197 TI - Focused and Radial Shock Wave Therapy in the Treatment of Tennis Elbow: A Pilot Randomised Controlled Study. AB - The purpose of this article was to evaluate and compare the efficacy of radial and focused shock wave therapies applied to treat tennis elbow. Patients with tennis elbow were randomized into two comparative groups: focused shock wave therapy (FSWT; n=25) and radial shock wave therapy (RSWT; n=25). Subjects in the FSWT and RSWT groups were applied with a focused shock wave (3 sessions, 2000 shocks, 4 Hz, 0.2 mJ/mm(2)) and a radial shock wave (3 sessions, 2000 + 2000 shocks, 8 Hz, 2.5 bar), respectively. The primary study endpoints were pain relief and functional improvement (muscle strength) one week after therapy. The secondary endpoint consisted of the results of the follow-up observation (3, 6 and 12 weeks after the study). Successive measurements showed that the amount of pain patients felt decreased in both groups. At the same time grip strength as well as strength of wrist extensors and flexors of the affected extremity improved significantly. Both focused and radial shock wave therapies can comparably and gradually reduce pain in subjects with tennis elbow. This process is accompanied by steadily improved strength of the affected extremity. PMID- 26557198 TI - Analysis of the Association Between Motor and Anthropometric Variables with Change of Direction Speed and Reactive Agility Performance. AB - There is an evident lack of studies examining the factors associated with reactive agility performances. The aim of this study was to evaluate the association between anthropometrics, body composition, jumping capacity, reactive strength, and balance with a stop-and-go change of direction speed (CODS) and reactive agility. The total sample comprised 39 male (body height: 182.95 +/- 5.19 cm; body mass: 80.66 +/- 7.69 kg) and 34 female (body height: 171.45 +/- 6.81 cm; body mass: 61.95 +/- 6.70 kg) college-level athletes (21.9 +/- 1.9 years of age). The variables included body height, body mass, the percentage of body fat (BF%), balance as measured by an overall-stability index, the countermovement jump (CMJ), a reactive-strength index (RSI), stop-and-go reactive agility, and stop-and-go CODS. To define the associations between motor and anthropometric variables with CODS and reactive agility, the participants were clustered into three achievement groups based on their CODS and reactive agility performances. The ANOVA showed a significant difference between the CODS-based achievement groups for the CMJ (F test = 3.45 and 3.60 for males and females, respectively; p < 0.05), the RSI (F test = 6.94 and 5.29 for males and females, respectively; p < 0.05), and balance (F test = 3.47; p < 0.05 for males). In females, the reactive agility achievement groups differed significantly in the RSI (F test = 6.46; p < 0.05), the CMJ (F test = 4.35; p < 0.05) and BF% (F test = 4.07; p < 0.05), which is further confirmed by discriminant canonical analysis (Can R = 0.74; p < 0.05). The results confirm the need for independent evaluation and training for both CODS and reactive agility performance in sports. PMID- 26557199 TI - Moderate Altitude Affects High Intensity Running Performance in a Collegiate Women's Soccer Game. AB - The effect of altitude on soccer game activity profiles was retrospectively examined in six NCAA Division I female soccer players. Comparisons were made between two matches played at sea level (SL) and one match played at a moderate altitude (1839 m). A 10-Hz global positioning system device was used to measure distance and velocity. The rate of total distance capacity (TDC) and high intensity running (HIR) as well as percent of time at HIR were evaluated. Significant differences were seen in the distance rate (120.55 +/- 8.26 m.min-1 versus 105.77 +/- 10.19 m.min-1) and the HIR rate (27.65 +/- 9.25 m.min-1 versus 25.07 +/- 7.66 m.min-1) between SL and altitude, respectively. The percent of time at HIR was not significantly different (p = 0.064), yet tended to be greater at SL (10.4 +/- 3.3%) than at altitude (9.1 +/- 2.2%). Results indicate that teams residing at SL and competing at a moderate altitude may have a reduced ability in distance covered and a high intensity run rate. PMID- 26557200 TI - Effects of Traditional Versus Horizontal Inertial Flywheel Power Training on Common Sport-Related Tasks. AB - This study aimed to analyze the effects of power training using traditional vertical resistance exercises versus direction specific horizontal inertial flywheel training on performance in common sport-related tasks. Twenty-three healthy and physically active males (age: 22.29 +/- 2.45 years) volunteered to participate in this study. Participants were allocated into either the traditional training (TT) group where the half squat exercise on a smith machine was applied or the horizontal flywheel training (HFT) group performing the front step exercise with an inertial flywheel. Training volume and intensity were matched between groups by repetitions (5-8 sets with 8 repetitions) and relative intensity (the load that maximized power (Pmax)) over the period of six weeks. Speed (10 m and 20 m), countermovement jump height (CMJH), 20 m change of direction ability (COD) and strength during a maximal voluntary isometric contraction (MVIC) were assessed before and after the training program. The differences between groups and by time were assessed using a two-way analysis of variance with repeated measures, followed by paired t-tests. A significant group by time interaction (p=0.004) was found in the TT group demonstrating a significantly higher CMJH. Within-group analysis revealed statistically significant improvements in a 10 m sprint (TT: -0.17 0.27 s vs. HFT: -0.11 0.10 s), CMJH (TT: 4.92 2.58 cm vs. HFT: 1.55 2.44 cm) and MVIC (TT: 62.87 79.71 N vs. HFT: 106.56 121.63 N) in both groups (p < 0.05). However, significant differences only occurred in the 20 m sprint time in the TT group (-0.04 0.12 s; p = 0.04). In conclusion, the results suggest that TT at the maximal peak power load is more effective than HFT for counter movement jump height while both TT and HFT elicited significant improvements in 10 m sprint performance while only TT significantly improved 20 m sprint performance. PMID- 26557201 TI - Effects of Single Vs. Multiple Sets Water-Based Resistance Training on Maximal Dynamic Strength in Young Men. AB - The aim of this study was to compare the effects of single vs. multiple sets water-based resistance training on maximal dynamic strength in young men. Twenty one physically active young men were randomly allocated into 2 groups: a single set group (SS, n=10) and a multiple sets group (MS, n=11). The single set program consisted of only 1 set of 30 s, whereas the multiple sets comprised 3 sets of 30 s (rest interval between sets equaled 1 min 30 s). All the water-based resistance exercises were performed at maximal effort and both groups trained twice a week for 10 weeks. Upper (bilateral elbow flexors and bilateral elbow extensors, peck deck and inverse peck deck) as well as lower-body (bilateral knee flexors and unilateral knee extensors) one-repetition maximal tests (1RM) were used to assess changes in muscle strength. The training-related effects were assessed using repeated measures two-way ANOVA (alpha=5%). Both SS and MS groups increased the upper and lower-body 1RM, with no differences between groups. Therefore, these data show that the maximal dynamic strength significantly increases in young men after 10 weeks of training in an aquatic environment, although the improvement in the strength levels is independent of the number of sets performed. PMID- 26557202 TI - Physical Demands of Top-Class Soccer Friendly Matches in Relation to a Playing Position Using Global Positioning System Technology. AB - The aim of this study was to examine the physical demands imposed on professional soccer players during 11-a-side friendly matches in relation to their playing position, using global positioning system (GPS) technology. One hundred and eleven match performances of a Spanish "La Liga" team during the 2010-11 and 2011 12 pre-seasons were selected for analysis. The activities of the players were monitored using GPS technology with a sampling frequency of 1 Hz. Total distance covered, distance in different speed categories, accelerations, and heart rate responses were analyzed in relation to five different playing positions: central defenders (n=23), full-backs (n=20), central midfielders (n=22), wide midfielders (n=26), and forwards (n=20). Distance covered during a match averaged 10.8 km, with wide and central midfielders covering the greatest total distance. Specifically, wide midfielders covered the greatest distances by very high intensity running (>19.8 km.h-1) and central midfielders by jogging and running (7.2-19.7 km.h-1). On the other hand, central defenders covered the least total distance and at high intensity, although carried out more (p<0.05-0.01) accelerations than forwards, wide midfielders, and fullbacks. The work rate profile of the players obtained with the GPS was very similar to that obtained with semi-automatic image technologies. However, when comparing results from this study with data available in the literature, important differences were detected in the amount of distance covered by sprinting, which suggests that caution should be taken when comparing data obtained with the GPS with other motion analysis systems, especially regarding high-intensity activities. PMID- 26557203 TI - Validation and Reliability of a Novel Test of Upper Body Isometric Strength. AB - The purpose of the present investigation was to examine the association of a novel test of upper body isometric strength against a 1RM bench press measurement. Forty college age adults (n = 20 female, n = 20 male; age 22.8 +/- 2.8 years; body height 171.6 +/- 10.8 cm; body mass 73.5 +/- 16.3 kg; body fat 23.1 +/- 5.4%) volunteered for the present investigation. The participants reported to the lab on three occasions. The first visit included anthropometric measurements and familiarization with both the upper body isometric test and bench press exercise. The final visits were conducted in a randomized order, with one being a 1RM assessment on the bench press and the other consisting of three trials of the upper body isometric assessment. For the isometric test, participants were positioned in a "push-up" style position while tethered (stainless steel chain) to a load cell (high frequency) anchored to the ground. The peak isometric force was consistent across all three trials (ICC = 0.98) suggesting good reliability. Multiple regression analysis was completed with the predictors: peak isometric force, gender, against the outcome variable 1RM bench press. The analysis resulted in a significant model (r2 = 0.861, p<=0.001) with all predictor variables attaining significance in the model (p<0.05). Isometric peak strength had the greatest effect on the model (Beta = 5.19, p<=0.001). Results from this study suggest that the described isometric upper body strength assessment is likely a valid and reliable tool to determine strength. Further research is warranted to gather a larger pool of data in regard to this assessment. PMID- 26557204 TI - Structural Analysis of Technical-Tactical Elements in Table Tennis and their Role in Different Playing Zones. AB - For the purpose of determining the overall structure of technical-tactical elements in table tennis and evaluating their role in different playing zones around the table, a new measuring instrument (a questionnaire) was formulated that took advantage of the expert knowledge of top, world class table tennis coaches. The results of the hierarchical taxonomic (cluster) analysis showed that the overall structure of the technical-tactical elements forming the table tennis technique could be divided into three basic groups; a group of technical-tactical elements (A) used in the phase of preparing one's own and disabling the opponent's attack; a group of technical-tactical elements (B) used in the phase of attack and counterattack; and a group of technical-tactical elements (C) used in the phase of defense. The differences among the obtained groups of table tennis elements were determined by applying the Kruskal-Wallis test, while relations between the groups and their role in different playing zones around the table were analyzed by comparing the average values of the experts' scores. PMID- 26557205 TI - The Structure of Morpho-Functional Conditions Determining the Level of Sports Performance of Young Badminton Players. AB - The aim of the study was to determine the structure of morpho-functional models that determine the level of sports performance in three consecutive stages of training of young badminton players. In the course of the study, 3 groups of young badminton players were examined: 40 preadolescents aged 11-13, 32 adolescents aged 14-16, and 24 adolescents aged 17-19. The scope of the study involved basic anthropometric measurements, computer tests analysing motor coordination abilities, motor skills encompassing speed, muscular power and strength, and cardiorespiratory endurance. Results of the study indicate that the structure of morpho-functional models varies at different stages of sports training. Sets of variables determining sports performance create characteristic complexes of variables that do not constitute permanent models. The dominance of somatic features and coordination abilities in the early stages of badminton training changes for the benefit of speed and strength abilities. PMID- 26557206 TI - Analysis of Soccer Players' Positional Variability During the 2012 UEFA European Championship: A Case Study. AB - The purpose of this study was to analyse players' positional variability during the 2012 UEFA European Championship by applying principal component analysis (PCA) to data gathered from heat maps posted on the UEFA website. We analysed the teams that reached the finals and semi-finals of the competition. The players' 2D coordinates from each match were obtained by applying an image-processing algorithm to the heat maps. With all the players' 2D coordinates for each match, we applied PCA to identify the directions of greatest variability. Then, two orthogonal segments were centred on each player's mean position for all matches. The segments' directions were driven by the eigenvectors of the PCA, and the length of each segment was defined as one standard deviation around the mean. Finally, an ellipse was circumscribed around both segments. To represent player variability, segment lengths and elliptical areas were analysed. The results demonstrate that Portugal exhibited the lowest variability, followed by Germany, Spain and Italy. Additionally, a graphical representation of every player's ellipse provided insight into the teams' organisational features throughout the competition. The presented study provides important information regarding soccer teams' tactical strategy in high-level championships that allows coaches to better control team organisation on the pitch. PMID- 26557207 TI - Relative Age Effect in UEFA Championship Soccer Players. AB - Relative Age Effect (RAE) is the breakdown by both age grouping and dates of birth of athletes. In the past 20 years the existence of this effect has been shown with higher or smaller impact in multiple sports, including soccer. The purpose of this study was to identify the existence of RAE in European soccer players. The sample included 841 elite soccer players who were participants in the UEFA European Soccer Championship in different categories. The professional category (n = 368), U-19 (n = 144) and U-17 (n = 145) were in 2012, and U-21 was in 2011 (n = 184). The Kolmogorov-Smirnov test and the Levene test recommended the use of nonparametric statistics. The results obtained by the square test ( the Kruskal-Wallis test and Cohen's effect sizes revealed the existence of RAE (chi(2) = 17.829, p < 0.001; d = 0.30), with the size of their different effects depending on their category or qualifying round achieved by the national team and the existence of significance in the observed differences by category. Therefore, we could continue examining RAE which is present in elite soccer, and could be considered a factor that influences performance of the national teams tested. RAE was not evident in the professional teams analysed, however it was present in the three lower categories analysed (youth categories), with its influence being greater on younger age categories (U-17). PMID- 26557208 TI - Attack Coverage in High-Level Men's Volleyball: Organization on the Edge of Chaos? AB - Change is pervasive, but emerging patterns are occasionally detectable through analysis of systemic behaviors. Match analysis uses these patterns in order to reduce the degree of improvisation and to optimize the training process. However, it is possible that certain game phases elude systematic patterning. In this vein, our aim was to analyze the case of attack coverage in men's volleyball, as we suspected it would elude systematic patterning and has received negligible attention in scientific research. We analyzed the occurrence of attack coverage in 4544 plays of the 2011 Volleyball World League. A Chi-square test with residual adjusted values was applied to explore significant associations between variables. A Monte Carlo correction was applied, as some cells had n<5. Effect sizes were determined using Cramer's V. Overall, attack coverage occurred in 3.89% of ball possessions, and 23 distinct structures emerged. These structures lacked significant associations with the game complex, setting zone, and effect of attack coverage. Conversely, attack coverage structures showed significant associations with the attack zone and tempo, with very strong effect sizes (V=0.472 and V=0.521, respectively). As certain attack zones are deeply associated with attack tempo, it is apparent that quicker attack plays affect attack coverage structuring, promoting the formation of less complex structures. Ultimately, attack coverage structures seem to depend on momentary constraints, thereby rendering rigid systematization impracticable. Still, we contended that a principle-based approach might be suitable. This invites researchers to rethink how to interpret game regularities. PMID- 26557209 TI - Influence of the Type of Marking and the Number of Players on Physiological and Physical Demands During Sided Games in Soccer. AB - The aim of this research was to examine the influence of two variables, the type of marking (with or without man-marking) and the number of players per team (3, 6, or 9) on the physical and physiological demands of sided games in soccer. Eighteen amateur players were monitored with GPS and heart rate devices. The following variables were analyzed: a maximum heart rate, a mean heart rate, time spent in each intensity range, total distance covered and distance covered in different speed ranges, a player load, maximum speed reached, and a work:rest ratio. The results showed that the type of marking influenced the physical demands of players, with greater total distance, a player load and a work:rest ratio when man-marking was used in the 3 vs. 3 (737 m, 95 Arbitrary Units (AU) and 3.4 AU, respectively) and 6 vs. 6 (783 m, 95 AU and 5.3 AU, respectively) games (p<0.05). The number of players also had an effect on physiological intensity, with more time being spent at the <80%HRmax during the 9 vs. 9 and 6 vs. 6 games (more than 30%) compared with the 3 vs. 3 format (less than 15%) (p<0.05). These findings could help coaches to understand how the modification of different variables in sided games influences the physical and physiological demands of players. PMID- 26557210 TI - The Intricacies of Children's Physical Activity. AB - Understanding the physical activity patterns of youth is an essential step in preparing programming and interventions needed to change behavior. To date, little is known about the intricacies of youth physical activity across various physical activity segments (i.e. in school, out of school, recess, classroom physical activity, physical education, weekends, etc.). Therefore, the purpose of the study was to examine the physical activity patterns of elementary school children across various segments and during two seasons. A total of 287 fourth and fifth graders from the Southwest US wore the Yamax Digiwalker SW-200 pedometer for 7 consecutive days during the Fall and Spring seasons. Children were prompted to record their step counts when arriving and leaving school, before and after physical education and recess, as well as on the weekends. Means and standard deviations were calculated and ANOVAs and t tests were utilized to examine difference by sex, season, and segment. Youth were more active outside of school and on weekdays (p<0.05). Boys were generally more active than girls and all youth were more active during the milder Spring season. There is a clear need for Comprehensive School Physical Activity Programming and weekend physical activity opportunities. Furthermore, greater emphasis is needed on PE and across other activity segments for girls to increase their physical activity levels. PMID- 26557211 TI - COMBINING NONEXCHANGEABLE FUNCTIONAL OR SURVIVAL DATA SOURCES IN ONCOLOGY USING GENERALIZED MIXTURE COMMENSURATE PRIORS. AB - Conventional approaches to statistical inference preclude structures that facilitate incorporation of supplemental information acquired from similar circumstances. For example, the analysis of data obtained using perfusion computed tomography to characterize functional imaging biomarkers in cancerous regions of the liver can benefit from partially informative data collected concurrently in non-cancerous regions. This paper presents a hierarchical model structure that leverages all available information about a curve, using penalized splines, while accommodating important between-source features. Our proposed methods flexibly borrow strength from the supplemental data to a degree that reflects the commensurability of the supplemental curve with the primary curve. We investigate our method's properties for nonparametric regression via simulation, and apply it to a set of liver cancer data. We also apply our method for a semiparametric hazard model to data from a clinical trial that compares time to disease progression for three colorectal cancer treatments, while supplementing inference with information from a previous trial that tested the current standard of care. PMID- 26557213 TI - A role for lung retention in the sense of retronasal smell. AB - In olfaction, odors typically engage the lungs on the way to the nose to evoke retronasal smell. This is most notable when the lung has a first pass effect during smoking/vaping, but also upon exhaling after sniffing an odor. The lungs act as a sink for odors, which can both reduce the retronasal odor concentration and the odor mixture makeup. Lung retention is a simple measure that quantifies the effectiveness of the sink. Lung retention has been studied in the context of environmental toxicology and is known for many volatile organic compounds. Available data on human lung retention suggests that the lungs may have a large impact on odor perception, and that this may depend heavily on the specifics of active sampling such as sniffing, smoking and vaping. Suggestions are included for transient measures and models of lung retention. PMID- 26557214 TI - Evaluation of Optical Coherence Tomography as a Means of Identifying Earlier Stage Basal Cell Carcinomas while Reducing the Use of Diagnostic Biopsy. AB - OBJECTIVE: To determine the diagnostic accuracy of optical coherence tomography for basal cell carcinoma and the proportion of biopsies that could be avoided if optical coherence tomography is used to rule-in surgery. DESIGN: Multicenter, prospective, observational study. SETTING: Dermatology clinics. PARTICIPANTS: Consecutive patients with clinically challenging pink lesions suspicious for basal cell carcinoma. MEASUREMENTS: Clinical, dermoscopic, and optical coherence tomography images were obtained for all subjects. At each stage, the clinician made a diagnosis (pathology + subtype if applicable), and assessed his/her own confidence in the diagnosis. RESULTS: Optical coherence tomography significantly (p<0.01) improved sensitivity and specificity over clinical or dermoscopic evaluation. The percentage of correct diagnoses was 57.4 percent (clinical), 69.6 percent (dermoscopy), and 87.8 percent (optical coherence tomography). Optical coherence tomography significantly increased the certainty of diagnosis; clinicians indicated they were certain (>95% confident) in 17 percent of lesions examined clinically, in 38.6 percent examined with dermoscopy, and in 70 percent examined with optical coherence tomography. With the use of optical coherence tomography in the diagnosis of basal cell carcinoma, more than 1 in 3 patients could avoid a diagnostic biopsy. CONCLUSION: In a population of clinically challenging lesions, optical coherence tomography improved diagnostic certainty by a factor of four over clinical examination alone and improved diagnostic accuracy by 50 percent (57-88%). The addition of optical coherence tomography to other standard assessments can improve the false-positive rate and give a high degree of certainty for ruling in a positive diagnosis for basal cell carcinoma. A reduction of 36 percent in overall biopsies could be achieved by sending high certainty basal cell carcinoma positive optical coherence tomography diagnoses straight to surgery. PMID- 26557215 TI - The Tolerability and Efficacy of a Three-product Anti-aging Treatment Regimen in Subjects with Moderate-to-severe Photodamage. AB - Retinoids and alpha hydroxy acids differ in mechanism of action for treatment of photodamage, but concurrent use may produce a synergistic effect by combining retinoid-induced normalization of cellular differentiation with alpha hydroxy acid-induced exfoliation (in hydrophilic areas) and enhanced dermal and epidermal hydration. A recent bioengineered molecule, ethyl lactyl retinoate (alpha hydroxy acid retinoid conjugate), is the first to deliver alpha hydroxy acids and retinoids together in a hydrolysis-based time-released fashion. This could improve efficacy while minimizing irritation commonly associated with retinoid use. An eight-week clinical study was conducted to examine the efficacy and tolerability of this formulation; 25 women aged 54.1 +/-8.9 years (mean +/- SD) with moderate-to-severe photodamage (as determined by physician investigators using the Glogau Wrinkle Scale) employed a twice-daily regimen of cleanser (7.8% 1-lactic acid, 2% salicylic acid) and anti-aging serum (0.1% alpha hydroxy acids retinoids, 6.5% 1-lactic acid) with concurrent use of sun protection factor 50+ sunscreen as needed. Longitudinal analysis of study data revealed statistically significant improvement in photodamage, dryness/flaking, dyschromia, and global appearance at eight weeks. All study products were well-tolerated throughout. Investigators concluded that the alpha hydroxy acid retinoid conjugate is a safe and effective topical therapy for moderate-to-severe photodamage, warranting further study, (clinicaltrials.gov, NCT02422836, https://clinicaltrials.gov/ct2/show/NCT02422836?term=NCT02422836). PMID- 26557216 TI - The Impact of Multispectral Digital Skin Lesion Analysis on German Dermatologist Decisions to Biopsy Atypical Pigmented Lesions with Clinical Characteristics of Melanoma. AB - OBJECTIVE: To determine the impact of multispectral digital skin lesion analysis on German dermatologist biopsy decisions of atypical pigmented skin lesions. DESIGN: Participants were shown high-resolution clinical images of 12 atypical pigmented skin lesions previously analyzed by multispectral digital skin lesion analysis. Participants were asked if they would biopsy the lesion based on clinical images and high-resolution dermoscopy images and again when subsequently shown multispectral digital skin lesion analysis probability information. SETTING/PARTICIPANTS: Forty-one dermatologists at a skin cancer conference in Germany in September 2014. MEASUREMENTS: Sensitivity, specificity, diagnostic accuracy, percent biopsying all melanomas, and overall biopsy rates. RESULTS: Sensitivity for the detection of melanoma following clinical evaluation was 64 percent. After receipt of multispectral digital skin lesion analysis probability information, sensitivity decreased nonsignificantly to 62 percent. Specificity with clinical evaluation was 57 percent and increased to 73 percent using multispectral digital skin lesion analysis. Overall biopsy accuracy increased from 60 percent with clinical evaluation to 68 percent with multispectral digital skin lesion analysis. The percentage of low-grade dysplastic nevi chosen for biopsy decreased from 43 percent after clinical evaluation to 27 percent with multispectral digital skin lesion analysis. Finally, the overall percentage of lesions biopsied decreased from 52 percent with clinical evaluation to 42 percent after multispectral digital skin lesion analysis. CONCLUSION: Multispectral digital skin lesion analysis can be used reliably to detect melanoma as well as clinical evaluation. Dermatologists can confidently use multispectral digital skin lesion analysis to significantly improve specificity and reduce their overall number of biopsies while increasing overall diagnostic accuracy. PMID- 26557217 TI - Rosacea Patient Perspectives on Homeopathic and Over-the-counter Therapies. AB - BACKGROUND: Rosacea patients commonly employ nonprescription therapies. The authors' aim was to understand rosacea patients' perceptions of over-the-counter products, complementary and alternative medicine, and homeopathic therapies. METHOD: A public, online discussion forum comprising 3,350 members and 27,051 posts provided a source of 346 posts on patient perceptions on alternative rosacea treatments. RESULTS: Three major themes of nonprescription treatment were identified-motivation for use, patient-provider discussions, and experience with these treatments. Perceived medication failure, barriers to treatment, and distrust of physicians drive patients to seek nonprescription therapies. Still, patients prefer to consult a physician on incorporating nonprescription therapies into treatment. Complementary and alternative medicine natural products (19.4% of posts), complementary and alternative medicine practices (16.5%), and homeopathic medicine (3.8%) were commonly discussed. CONCLUSION: Physicians have an opportunity to be a trusted source of information on the strengths and weaknesses of skin care products and other complementary treatments for rosacea. PMID- 26557218 TI - Injuries Attributable to Cosmetic Procedures Performed by Unlicensed Individuals in the United States. AB - OBJECTIVE: Although only licensed professionals should be performing cosmetic procedures for patients, there are often news stories of unlicensed individuals performing procedures with serious consequences. This brief report seeks to determine the scope and magnitude of the problem by determining the number of cases of unlicensed procedures and determining the people, procedures, and states that are involved. DESIGN: Various databases were used to find lawsuits and United States English-language news reports from January 1, 2013, through December 31, 2013, which described cosmetic procedures performed by unlicensed individuals. SETTING: The United States. PARTICIPANTS: All publicly reported cases. MEASUREMENTS: Number of cases, case location, type of procedures and injuries, and demographics of the victims and perpetrators. RESULTS: Twenty-eight unique cases were found. The three states with the highest number of cases were Florida (35.7%; n=10), Texas (14.3%; n=4), and California (10.7%; n=3). The type of procedures (n=28) performed were buttocks injections (n=1), face injections (n=7), laser facial procedures (n=2), liposuctions (n=4), and other cosmetic surgeries (n=4). The reported injuries (n=16) were hospitalization (n=8), death (n=4), amputation (n=1), burn (n=1), ptosis (n=1), and scar (n=1). Women and minorities appeared to be disproportionately affected by these illegal procedures. CONCLUSION: This study likely only provides a small snapshot of a much larger problem, as many cases are presumably not taken to the news or courts. The availability of illegal cosmetic procedures can be diminished with complementary efforts carried out both by law enforcement and the communities themselves. PMID- 26557212 TI - Using Animal Models to Determine the Role of Gustatory Neural Input in the Control of Ingestive Behavior and the Maintenance of Body Weight. AB - INTRODUCTION: Decades of research have suggested that nutritional intake contributes to the development of human disease, mainly by influencing the development of obesity and obesity-related conditions. A relatively large body of research indicates that functional variation in human taste perception can influence nutritional intake as well as body mass accumulation. However, there are a considerable number of studies that suggest that no link between these variables actually exists. These discrepancies in the literature likely result from the confounding influence of a variety of other, uncontrolled, factors that can influence ingestive behavior. STRATEGY: In this review, the use of controlled animal experimentation to alleviate at least some of these issues related to the lack of control of experimental variables is discussed. Specific examples of the use of some of these techniques are examined. DISCUSSION AND CONCLUSIONS: The review will close with some specific suggestions aimed at strengthening the link between gustatory neural input and its putative influence on ingestive behaviors and the maintenance of body weight. PMID- 26557219 TI - The "Knife-Cut Sign" Revisited: A Distinctive Presentation of Linear Erosive Herpes Simplex Virus Infection in Immunocompromised Patients. AB - BACKGROUND: The "knife-cut sign" is a distinctive presentation of linear erosive herpes simplex virus infection in immunocompromised patients. PURPOSE: To describe a man whose herpes simplex virus infection-related skin lesions demonstrated the "knife-cut sign" and to review the characteristics of reported immunosuppressed individuals with "knife-cut" cutaneous herpes simplex virus lesions. METHODS: A man with multiple myeloma and post-stem cell transplant cutaneous graft-versus-host disease managed with systemic prednisone and sirolimus developed disseminated cutaneous herpes simplex virus infection with virus-associated linear ulcers of the inguinal folds and the area between his ear and scalp; the lesions at both sites had a distinctive "knife-cut" appearance. Using the PubMed database, an extensive literature search was performed on herpes simplex virus, immunocompromised patient, and "knife-cut sign". RESULTS: Herpes simplex virus infection-associated skin lesions that demonstrate the "knife-cut sign" present in patients who are immunosuppressed secondary to either an underlying medical condition or a systemic therapy or both. The distinctive virus related cutaneous lesions appear as linear ulcers and fissures in intertriginous areas, such as the folds in the inguinal area, the vulva, and the abdomen; in addition, other sites include beneath the breast, within the gluteal cleft, and the area between the ear and the scalp. Not only herpes simplex virus-2, but also herpes simplex virus-1 has been observed as the causative viral serotype; indeed, herpes simplex virus-1 has been associated with genital and inframammary lesions in addition to those above the neck. Direct fluorescent antibody testing is a rapid method for confirming the clinically suspected viral infection; however, since false-negative direct fluorescent antibody testing occurred in some of the patients, it may be prudent to also perform viral cultures and possibly lesional skin biopsies to establish the diagnosis. The herpes simplex virus infection related skin lesions clinically improve once systemic antiviral therapy is initiated. CONCLUSION: In immunosuppressed individuals, the "knife-cut sign" is a distinctive presentation of cutaneous linear erosive herpes simplex virus infection. Recognition of the linear ulcers in intertriginous areas and body folds should prompt the clinician to consider herpes simplex virus infection associated skin lesions in an immunocompromised patient and to initiate systemic antiviral treatment while awaiting the results of laboratory evaluation to confirm the suspected diagnosis. PMID- 26557220 TI - Linear IgA Bullous Dermatosis: A Rare Clinicopathologic Entity with an Unusual Presentation. AB - Linear immunoglobulin A bullous dermatosis is a rare autoimmune mucocutaneous disorder caused by immunoglobulin A autoantibodies produced against several different antigens in the basement membrane zone. Clinically, it is characterized by tense vesicles or bullae, which on histopathological exam demonstrate subepidermal blister with a predominantly neutrophilic infiltrate. A smooth, linear pattern of immunoglobulin A deposition in the basement membrane zone on direct immunofluorescence is considered the gold standard for establishing a diagnosis. Treatment consists of dapsone or sulfapyridine. The authors report a 60-year-old woman who presented with pruritic erythematous patches and plaques on her trunk, back, and legs without blisters, who was diagnosed with eczema for several months with no response to prior treatments. A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies. The authors present this case to increase awareness of this rare disease, which could manifest in a nonclassical, nonblistering fashion. PMID- 26557221 TI - Kids These Days: Urine as a Home Remedy for Acne Vulgaris? AB - Complementary and alternative medicine therapies are gaining popularity among patients, aided by modern media outlets that facilitate easy and rapid dissemination of information. "Urine therapy" is one such complementary and alternative medicine and is described by its proponents as a wonder therapy for inflammatory conditions, such as acne vulgaris. As with other complementary and alternative medicines, healthcare providers should be mindful of the use of urine therapy and its potential implications for patients who may utilize it. PMID- 26557223 TI - Compensation for Managing Population Health. PMID- 26557224 TI - Longitudinal Commercial Claims-Based Cost Analysis of Diabetic Retinopathy Screening Patterns. AB - BACKGROUND: Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service. OBJECTIVE: To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes. METHODS: Truven Health MarketScan commercial databases (2000-2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001-2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001-2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1-4, 5-7, and 8-10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables. RESULTS: In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts' mean incremental cost increase was $185 between the 0- and 1-4-year cohorts (P <.003) and $202 between the 0- and 5-7-year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8-10-year cohorts (P <.066), were not statistically significant. CONCLUSIONS: Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened. PMID- 26557222 TI - Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury. AB - Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities. PMID- 26557225 TI - Evaluating Drug Cost per Response with SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus. AB - BACKGROUND: The sodium-glucose cotransporter 2 (SGLT2) inhibitors, which include canagliflozin, dapagliflozin, and empagliflozin, represent a new class of antihyperglycemic agents. Few studies have assessed their cost per response, with "cost per response" being the total cost of a select drug, divided by the resulting change in glycated hemoglobin (HbA1c) levels. OBJECTIVE: To examine the drug cost of SGLT2 inhibitors per a reduction in placebo-adjusted 1% HbA1c in patients with type 2 diabetes mellitus who received treatment during 26 weeks with canagliflozin, dapagliflozin, or empagliflozin. METHODS: The drug cost per response for each of the 3 agents individually was assessed based on data from a subset of clinical trials discussed in the prescribing information for each drug that were all placebo-controlled studies evaluating each drug as monotherapy, dual therapy (combined with metformin), and triple therapy (combined with metformin and a sulfonylurea) in patients with uncontrolled, type 2 diabetes mellitus. The US 2015 wholesale acquisition cost for each drug was used to calculate each drug's treatment costs over 26 weeks. The average cost per response for each drug was defined as the prescription drug cost of each SGLT2 inhibitor, divided by the average, placebo-adjusted HbA1c reduction at 26 weeks. RESULTS: The drug cost per unit dose was the same for canagliflozin (100 mg or 300 mg), dapagliflozin (5 mg or 10 mg), and empagliflozin (10 mg or 25 mg), at $11.43. The drug cost per placebo-adjusted 1% HbA1c reduction varied by agent and by dose, as a result of the differences in the treatment responses for each of the 3 drugs. The costs per response for canagliflozin 100 mg as monotherapy, dual therapy, and triple therapy regimens ranged from $2286 to $3355, and for canagliflozin 300 mg, from $1793 to $2702. The costs per response for dapagliflozin 5 mg as monotherapy and dual therapy (triple therapy was not available at the time of the study) ranged from $4161 to $5201; the cost for dapagliflozin 10 mg ranged from $2972 to $4161. The costs per response for empagliflozin 10 mg ranged from $2972 to $3467 across the monotherapy, dual therapy, and triple therapy regimens; the cost for empagliflozin 25 mg ranged from $2311 to $3467. CONCLUSION: Simple analyses, such as the drug cost per placebo-adjusted 1% reduction in HbA1c, may be useful when considering the addition of antihyperglycemic agents to the health plan's formulary. PMID- 26557226 TI - The Impact of HbA1c Testing on Total Annual Healthcare Expenditures Among Newly Diagnosed Patients with Diabetes. AB - BACKGROUND: In 2010, diabetes was the seventh leading cause of death in the United States. Diabetes also imposes a huge financial burden on the US economy. In 2009, the American Diabetes Association International Expert Committee recommended the use of the glycated hemoglobin (HbA1c) test as a uniform diagnostic measure to identify patients with diabetes. Although HbA1c is a convenient diagnostic test, it is also more expensive than older tests and could, therefore, have an impact on patients' healthcare expenditures. OBJECTIVES: To determine if HbA1c testing has an impact on total annual healthcare expenditures among newly diagnosed patients with diabetes and to analyze the factors that are associated with the total healthcare expenditures among diabetic patients before and after HbA1c was implemented as a standard diagnostic factor. METHODS: This was an observational, retrospective, cross-sectional study. The Medical Expenditure Panel Survey-Household Component 2009 and 2011 databases were used to form the study cohort of patients with diabetes. The total mean healthcare expenditures among patients with diabetes formed the dependent variable. A proxy variable representing a diagnosis of diabetes with and without the use of HbA1c testing in 2009 and in 2011, respectively, formed the main independent variable along with demographic factors, comorbidities, and healthcare services utilization in both years. A generalized linear regression was conducted to determine the association of HbA1c testing with total diabetes-related healthcare expenditures. RESULTS: The mean total healthcare expenditure decreased in 2011 compared with 2009. The HbA1c test did not show an association with the total healthcare expenditures versus earlier diabetes-related diagnostic factors. The total expenditures were associated with private insurance, the incidence of a previous heart attack, prescription drug refills, inpatient hospital stays, home care, hospital discharges, and visits to outpatient providers and physicians in both years. CONCLUSIONS: The HbA1c diagnostic factor did not yield any association with diabetes healthcare expenditures. Although the total healthcare expenditures were reduced in 2011 compared with 2009, it cannot be established that the reduction in costs is solely attributed to the implementation of the HbA1c diagnostic criteria. Further research on healthcare expenditures for diabetic patients diagnosed with and without the use of HbA1c testing is warranted to establish any possible association. PMID- 26557227 TI - Entresto (Sacubitril/Valsartan): First-in-Class Angiotensin Receptor Neprilysin Inhibitor FDA Approved for Patients with Heart Failure. PMID- 26557228 TI - Philly Firsts. PMID- 26557229 TI - Optimizing Rheumatoid Arthritis Therapy: Using Objective Measures of Disease Activity to Guide Treatment. AB - BACKGROUND: Rheumatoid arthritis (RA) affects approximately 1.5 million individuals in the United States, or approximately 1% of the US adult population. In women, RA most often begins between age 30 and 60 years; in men, it often starts later in life. Patients with RA may have rapid declines in physical function that can begin early in the disease course. Disability increases most rapidly during the early years of the disease course, and if patients are not accurately diagnosed and do not receive appropriate care early, substantial functional declines may result. OBJECTIVE: To review strategies and clinical assessment tools that may optimize patient outcomes by using objective measures of disease activity. DISCUSSION: The goal of treatment for patients newly diagnosed with RA should be preventing joint damage from developing by employing early and aggressive approaches to therapy that minimize disease activity. Likewise, for established disease, treatment should be aimed at limiting the progression of existing joint damage. Substantial advances have been made in the treatment of RA over the past 2 decades, in large part as a result of better understanding of the biology of RA and the resultant introduction of biologic therapies. In 2010, an international task force published recommendations for a treat-to-target management approach to RA, much of which was based on the use of biologic drugs. This treatment strategy emphasized that the primary target in the treatment of patients with RA should be clinical remission or low disease activity. The tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations. There is no one symptom, laboratory measure, or clinical tool that provides a truly accurate assessment of disease activity in patients with RA. CONCLUSION: Thus, there is a large gap between what is recommended in clinical guidelines and the actual practice of rheumatologists. Better methods of assessing RA disease activity are still needed to enable widespread adoption of guidelines in the clinical community. PMID- 26557231 TI - Transforming the Drug Cost Paradigm from Payment for Medications to Payment for Value. PMID- 26557230 TI - Evaluating the Expected Costs and Budget Impact of Interventional Therapies for the Treatment of Chronic Venous Disease. AB - BACKGROUND: Chronic venous disease is a common disorder in the United States. The manifestations of chronic venous disease include varicosities and related sequelae that are frequent contributors to the morbidity and high costs associated with the disease. The interventional treatment options for chronic venous disease have expanded greatly in recent years and include various surgical and vein ablation techniques. Polidocanol injectable foam (also known as polidocanol endovenous microfoam 1%), a chemical ablation agent, is the most recent entrant to the market. OBJECTIVE: To evaluate the expected patient-level total treatment costs and health plan-level budgetary impact of polidocanol injectable foam compared with the currently available interventional treatment options from a third-party US payer perspective. METHODS: A Microsoft Excel-based budget impact model was designed to compare the costs of polidocanol injectable foam with other interventional treatments (ie, laser ablation, radiofrequency ablation, surgery, and multimodality treatment). The model included drug acquisition, medical procedure, administration, additional treatment, and disease progression costs. The treatment patterns and rates of additional treatment were incorporated from a recent retrospective claims analysis for established treatment modalities and from the clinical trials for polidocanol injectable foam. The model estimates the 1-year total estimated costs and the health plan budget impact assuming an 8-week treatment time frame. RESULTS: The total expected 8-week treatment costs were $2165 for polidocanol injectable foam, $1827 for endovenous laser ablation, $2106 for radiofrequency ablation, $2374 for surgery, and $2844 for multimodality treatment. The initial treatment costs were higher for surgery and multimodality treatment compared with polidocanol injectable foam and were lower for endovenous laser ablation and radiofrequency ablation treatments. Polidocanol injectable foam is projected to have a relatively small budget impact ($0.01 per member per month) at an initial 5% market share. CONCLUSION: Polidocanol injectable foam offers an alternative to other interventional options for the treatment of varicose veins and is projected to have a relatively small budget impact. From a health plan perspective, this drug is likely to have a relatively low budget impact as it becomes more widely used. PMID- 26557232 TI - Healthcare Utilization and Costs of Knee or Hip Replacements versus Pain-Relief Injections. AB - BACKGROUND: Given the dramatic increase in total knee and hip replacement procedures among the US population aged 45 years and older, there is a need to compare the downstream healthcare utilization and costs between patients who undergo joint replacement and those who receive intraarticular injections as a low-cost alternative. OBJECTIVE: To compare changes in osteoarthritis (OA) related healthcare utilization and costs for Medicare members with OA who underwent knee or hip replacement versus those receiving steroid or viscosupplementation injections. METHODS: Medicare members aged >=45 years diagnosed with OA were identified for this retrospective longitudinal study. Data were compared for patients who underwent primary knee or hip replacement surgery between July 1, 2007, and June 30, 2012, and those receiving injection of pain relief medication during the same period. The date of joint replacement surgery was considered the index date. For the comparison cohort, the index date was 180 days postinjection of the first intraarticular injection. Medical and pharmacy claims were examined longitudinally in 90-day increments, from 180 days preindex until 360 days postindex. Difference-in-difference analyses were conducted to compare the change in OA-related healthcare costs, postindex versus preindex, between the study cohorts. Time-to-event analyses were used to measure rates of readmissions and venous thromboembolism (VTE). RESULTS: The mean age was 70.7 years for patients with knee replacement, 71.7 years for those with hip replacement, and 71.1 years for those receiving pain-relief injection (P <.0001). The RxRisk-V comorbidity index scores were 4.7, 4.4, and 4.8, respectively (P <.0001). Difference-in-difference analyses indicated that decreases in OA-related costs were greater for the joint replacement cohorts (coefficient for knee replacement*time: -0.603; hip replacement*time: -0.438; P <.001 for both) than for the comparison cohort. The VTE rates were 5.6% (knee) and 5.1% (hip) postsurgery versus 1.4% (knee) and 1.3% (hip) presurgery. CONCLUSION: The overall difference-in-difference results showed a greater decrease in healthcare utilization and costs for the members with joint replacement than for those receiving injection. PMID- 26557233 TI - Profuse coarse pulmonary nodules in a patient with lymphangioleiomyomatosis: thirty-three years of follow-up. AB - Lymphangioleiomyomatosis (LAM) is a rare disease characterized by progressive cystic destruction of the lungs. We present an unusual radiological presentation of lymphangioleiomyomatosis in a patient followed for 33 years with profuse coarse lung nodules in addition to the classical cystic lesions. We believe that this report might support the case for considering LAM a low-malignant neoplasm. PMID- 26557234 TI - Good clinical practice in clinical interventional studies. AB - Good clinical practice (GCP) guidelines should always be implemented and obeyed in clinical interventional studies. In this mini-review, we will address several burning questions relating to GCP in a concise 'frequently asked questions' format. While compliance to current rules and regulations is our mission, we also wish to play devil's advocate attempting to translate the rules into sizeable chunks using a high dose of common sense. PMID- 26557235 TI - Determinants of uncontrolled asthma in a Swedish asthma population: cross sectional observational study. AB - BACKGROUND: Asthma control is achieved in a low proportion of patients. The primary aim was to evaluate risk factors for uncontrolled asthma. The secondary aim was to assess quality of life associated with asthma control. METHODS: In a cross-sectional study, asthma patients aged 18-75 were randomly selected from primary and secondary health care centers. Postal questionnaires were sent to 1,675 patients and the response rate was 71%. A total of 846 patients from primary and 341 patients from secondary care were evaluated. Data were collected using a questionnaire and review of medical records. The questionnaire included questions about asthma control and a quality-of-life questionnaire, the mini AQLQ, with four domains (symptoms, activity limitation, emotional function, and environmental stimuli). The mean score for each domain and the overall score were calculated. Asthma control was divided into three levels according to the GINA guidelines and partly and uncontrolled asthma were combined into one group - poorly controlled asthma. RESULTS: Asthma control was achieved in 36% of the sample: 38% in primary and 29% in secondary care. In primary and secondary care, 35 and 45% had uncontrolled asthma, respectively. Risk factors for poorly controlled asthma were female sex [OR 1.31 (1.003-1.70)], older age [OR 2.18 (1.28-3.73)], lower educational level [OR 1.63 (1.14-2.33)], and current smoking [OR 1.68 (1.16-2.43)]. Older age and lower educational level remained statistically significantly associated with poorly controlled asthma when the analyses were limited to never-smokers. Depression was an independent risk factor for poorly controlled asthma in men [OR 3.44 (1.12-10.54)]. The mini-AQLQ scores and the mean overall score were significantly lower in uncontrolled asthma. CONCLUSION: Risk factors for poorly controlled asthma were female sex, older age, low educational level, and smoking. Uncontrolled asthma was significantly associated with lower quality of life. PMID- 26557236 TI - The Bergen COPD microbiome study (MicroCOPD): rationale, design, and initial experiences. AB - BACKGROUND: Recent methodological developments, in particular new sequencing methods for bacterial RNA/DNA, have shown that microorganisms reside in airways that do not suffer from acute infection and that respiratory microbiota might vary according to airways disease status. We aim to establish high-quality sampling methods for lower airways microbiota as well as describe the respiratory microbiome in subjects with and without chronic obstructive pulmonary disease (COPD) and to relate the microbiome to disease development, progression, and the host immune system. METHODS: The Bergen COPD microbiome study (MicroCOPD) is a longitudinal study aiming to collect data from 200 subjects with COPD as well as 150 individuals without COPD. At baseline, subjects go through a bronchoscopy in which protected specimen brushes, small-volume lavage, bronchoalveolar lavage, and bronchial biopsies provide a unique chance to analyze the microbiota and the host immune system status. These variables will be related to baseline clinical parameters (lung function, smoking status, exacerbation frequency, arterial blood gases, comorbidities, and medications) as well as follow-up parameters (lung function changes, exacerbation frequency, mortality, and more). RESULTS: Per date more than 150 bronchoscopies have been performed, equally distributed between cases and controls, with a very low complication frequency. CONCLUSIONS: MicroCOPD will provide unique data on a large material, with insight on a new field of respiratory research. PMID- 26557237 TI - Inflammatory myofibroblastic tumor: a rare tumor of the lung. AB - Inflammatory myofibroblastic tumor (IMT) is a rare lesion, representing 0.04-1.2% of all lung tumors. Brunn first described it in 1939, but its etiology remains uncertain. A 16-year-old patient was admitted to our hospital for further examination following abnormal radiological findings. The physical examination showed no abnormality, and routine hematological and biochemical parameters were within normal range. Chest radiograph revealed homogenous opacity of the right upper lobe with regular margins. Thoracic CT showed a nodular lesion, 30*26 mm in dimensions, with lobular contours in the right hilar. Bronchoscopic examination showed a vascular endobronchial lesion in the anterior right upper lobe, with bleeding when palpated. She underwent right thoracotomy for diagnostic and therapeutic purposes since bronchoscopic biopsy failed because of bleeding. With a pathological diagnosis of IMT, the present report discusses her case accompanied by relevant literature as it is a very rare type of lung tumor. IMT is a rare benign tumor. The diagnosis is difficult to make before surgery since its clinical and radiological features are variable and nonspecific. Although it is a benign lesion, it should be completely resected and patients should be closely monitored following the resection in order to avoid local invasion and recurrence. PMID- 26557238 TI - An obstructing endobronchial lipoma simulating COPD. AB - Endobronchial lipomas are rare benign tumors of the respiratory tract. Bronchial occlusion may cause parenchymal damage and lead to a misdiagnosis of chronic obstructive pulmonary disease or malignancy. Therefore, both accurate diagnosis and radical treatment of endobronchial lipomas are essential. We describe the case of a 61-year-old man with a history of smoking (40 pack years), dyspnea in exertion, and cough during the past 6 months due to an endobronchial lipoma. Chest computed tomographic (CT) scan revealed a circumscribed polypoid lesion partially obstructing the left lower lobe. The endobronchial lipoma was removed by flexible bronchoscopy, and the patient had complete resolution of symptoms following the procedure. Flexible bronchoscopy was normal at the 3-month follow up. In addition, clinical characteristics, diagnosis, and treatment of endobronchial lipomas are discussed. PMID- 26557239 TI - Methotrexate as an oral corticosteroid-sparing agent in severe asthma: the emergence of a responder asthma endotype. AB - BACKGROUND: Sustained use of oral corticosteroids is associated with significant side effects. It is therefore of interest to find a corticosteroid-sparing agent. In two meta-analyses, methotrexate resulted in a rather small reduction in the oral corticosteroid maintenance dose. We have used methotrexate as an oral corticosteroid-sparing agent in consecutive patients with severe bronchial asthma and find a need for a real-life observational study to evaluate the effect of methotrexate in clinical practice. METHODS: We analyzed the clinical data of 13 oral corticosteroid-dependent asthma patients with a mean prednisolone dose of 15 mg/day for up to 8 years. The diagnosis of asthma based on the clinical history, positive bronchodilator reversibility test, and variable airflow obstruction was secured by bronchial biopsies in all patients. We reviewed the literature and found 12 studies evaluating methotrexate as an oral corticosteroid-sparing agent in severe asthma and calculated the mean daily reduction in mg of prednisolone. RESULTS: Oral corticosteroids could be reduced in 8/13 patients, 61.5% (mean reduction 9.0 mg/day), and stopped in six of these patients. Five patients had no reduction and remained oral corticosteroid-dependent. Patients with the highest oral corticosteroid doses experienced the greatest reductions. Two patients stopped methotrexate due to side effects. FEV1 remained unaffected by methotrexate treatment and corticosteroid reduction. CONCLUSIONS: Methotrexate has significant oral corticosteroid-sparing effect while maintaining an unaltered asthma control and spirometry. Methotrexate seems an effective oral corticosteroid-sparing agent in a significant proportion of patients with severe asthma. The specific asthma phenotype/endotype that responds needs further study. PMID- 26557241 TI - The launch of the European Clinical Respiratory Journal, the scientific forum of the Nordic Respiratory Academy. PMID- 26557242 TI - Feasibility of a telecare solution for patients admitted with COPD exacerbation: screening data from a pulmonary ward in a university hospital. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Furthermore, the prevalence of COPD is increasing, and it places an increasing burden on health care systems worldwide. Therefore, there is a growing interest in home telecare solutions that can help patients manage their disease at home and thereby possibly reduce the risk of readmission. PURPOSE: The primary aim of this study is to assess the feasibility of a telehealth care solution when offered in connection with discharges from a pulmonary ward at a university hospital. Secondary aims are to assess the reasons for the exclusion of patients, and the reasons for patients not consenting to participate, as well as to identify the predictors for consenting or not consenting among the subgroup of eligible patients. METHODS: In this study, all data in the screening log were collected over a period of 10 months. RESULTS: A total of 462 patients admitted with an acute exacerbation in COPD (AECOPD) were screened. Almost 70% of the patients were excluded, and 49% of the eligible patients did not consent. Thus, only 15.6% of the screened patients were included. No significant differences were found regarding known risk factors of readmission between the eligible patients, who were included, and those who did not consent. The only significant difference was that more patients in the group that consented are being followed up in our outpatient clinic, notably 84% versus 55.7% (p<0.001), suggesting that this telehealthcare solution is 25 more appealing to those patients who are already being followed up in the outpatient clinic. CONCLUSION: These findings emphasize the importance of designing telecare solutions that allow for the inclusion of the actual population of patients admitted with AECOPD. PMID- 26557243 TI - Are patients with COPD treated with NIV in accordance with national guidelines? An internal audit. AB - INTRODUCTION: Non-invasive ventilation (NIV) as an add-on modality to medical treatment has been recommended in national guidelines for patients acutely admitted with chronic obstructive pulmonary disorder (COPD) exacerbation and hypercapnic respiratory failure. To address concerns regarding whether NIV is used appropriately, we conducted an audit of COPD patients admitted to a university hospital in Denmark. MATERIAL AND METHODS: Data from medical records were retrieved for two cohorts in 2010: 1) all patients admitted to the Medical Emergency Ward with the diagnosis of COPD, and 2) all patients receiving NIV regardless of their diagnosis at the Respiratory Ward. Demographic data and outcome of treatment were registered. RESULTS: Cohort 1 comprised 804 admissions fulfilling criteria for COPD at evaluation, and of the 804 admissions, NIV was initiated in 151 (18.7%) admissions. In 42 additional cases (5.2%), initial mild respiratory acidosis was registered at admission, fulfilling criteria for NIV treatment; and, in 36 cases, the clinical status was reported as improved or not reported at all; no deaths were observed. In cohort 2, 124 admissions were registered that comprised 110 admissions with COPD and 14 without a diagnosis of COPD (of which half had a 'not-to-intubate' order). The indication for NIV treatment was met in 92.7% of the COPD admissions. CONCLUSION: NIV was initiated in 18.8% of the COPD admissions, and in an additional 5.2%, NIV criteria were met without initiation. In 82.3% of the admissions receiving NIV, a COPD diagnosis and correct criteria for NIV treatment were met. PMID- 26557240 TI - Techniques of assessing small airways dysfunction. AB - The small airways are defined as those less than 2 mm in diameter. They are a major site of pathology in many lung diseases, not least chronic obstructive pulmonary disease (COPD) and asthma. The small airways are frequently involved early in the course of these diseases, with significant pathology demonstrable often before the onset of symptoms or changes in spirometry and imaging. Despite their importance, they have proven relatively difficult to study. This is in part due to their relative inaccessibility to biopsy and their small size which makes their imaging difficult. Traditional lung function tests may only become abnormal once there is a significant burden of disease within them. This has led to the term 'the quiet zone' of the lung. In recent years, more specialised tests have been developed which may detect these changes earlier, perhaps offering the possibility of earlier diagnosis and intervention. These tests are now moving from the realms of clinical research laboratories into routine clinical practice and are increasingly useful in the diagnosis and monitoring of respiratory diseases. This article gives an overview of small airways physiology and some of the routine and more advanced tests of airway function. PMID- 26557244 TI - Meta-analysis of routine blood tests as predictors of mortality in COPD. AB - OBJECTIVE: The purpose of this study was to examine whether routine blood tests can be useful in predicting mortality in COPD patients. METHODS: Eligible studies were found through a search conducted in the PubMed and Embase databases, the Cochrane Library, and the Web of Knowledge. Twelve studies were included for the meta-analysis of five biochemical markers. Pooled odds ratios (ORs), matching 95% confidence intervals (CIs), and p-values for each of the biochemical markers were calculated using the random effect model. RESULTS: The following four examined biochemical markers were shown to be associated with mortality in patients suffering from COPD: anemia (OR=2.62, 95% CI: 1.60; 4.29, p=0.01), hypoalbuminemia (OR=2.90, 95% CI: 1.56; 5.40, p=0.0008), elevated NT-proBNP (OR=7.54, 95% CI: 4.04; 14.10, p<0.00001), and elevated cardiac troponin T (OR=3.10, 95% CI: 1.11; 8.25, p=0.03). hs-CRP was not found to be associated with increased mortality. CONCLUSION: In this study, we found that anemia, hypoalbuminemia, elevated NT-proBNP, and elevated cardiac troponin T were associated with increased mortality in patients suffering from COPD. PMID- 26557245 TI - Defining severe asthma - an approach to find new therapies. AB - Asthma is a chronic inflammatory disease that has reached epidemic proportions worldwide. It is treatable in the majority of patients, but there is no cure. Moreover, a proportion of patients suffer from severe, difficult-to-control disease with daily symptoms and high morbidity, making it imperative that we continue to improve our understanding of the underlying mechanisms of this disease. Severe asthma is a heterogeneous condition. A systematic approach to identify specific asthma phenotypes, including clinical characteristics and inflammatory processes, is the first step toward individualized, logical therapy. This review focuses on the need to characterize severe asthma phenotypes and on novel, targeted molecular treatment options currently under development. PMID- 26557246 TI - Interactions between alveolar epithelial cells and neutrophils under pro inflammatory conditions. AB - BACKGROUND: Intercellular communication is essential for defense and survival of the organism. The aim of the study was to find out whether there is an active crosstalk between airway cells constituting the first line of defense, alveolar epithelial cells (A549) and neutrophils, following activation with pro inflammatory stimuli in vitro and to explore whether this communication is altered in chronic obstructive pulmonary disease (COPD), a condition characterized by chronic airway and lung inflammation. METHODS: Blood neutrophils from healthy subjects and COPD patients were co-cultured with A549 cells in pure medium and in medium containing lipopolysaccharide (LPS), peptidoglycan (PGN), or tumor necrosis factor. The expression of Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and CD14 on the cell surface of neutrophils was assessed by flow cytometry, and release of CXCL8 (IL-8) and the soluble CD14 (sCD14) was measured in the supernatant with enzyme-linked immunosorbent assay (ELISA). RESULTS: On neutrophils, the surface expression of TLR2 was diminished following activation with all three pro-inflammatory stimuli, and membrane bound (mCD14) and TLR4 expression were significantly increased in co-cultures compared to single cell cultures, irrespective of pro-inflammatory stimulation. There was a correlation between CXCL8 and sCD14 in LPS-stimulated co-cultured cells (r=0.82; p<0.01). CONCLUSION: An active crosstalk between A549 cells and blood neutrophils was clearly demonstrated, both in unstimulated cells and following activation with pro-inflammatory stimuli, in vitro. Co-culturing implied synergy and correlation between LPS-induced release of sCD14 and CXCL8, which indicates that sCD14 may be donated by neutrophils to epithelial cells facilitating TLR4 signaling. Furthermore, TLR2 on neutrophils was found to be down-regulated by pro inflammatory stimuli. PMID- 26557248 TI - Fabry disease, respiratory symptoms, and airway limitation - a systematic review. AB - BACKGROUND: Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. MATERIALS AND METHOD: A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review. RESULTS: The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry. CONCLUSION: Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment. PMID- 26557249 TI - Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD. AB - BACKGROUND: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke. METHODS: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13). RESULTS: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers. CONCLUSIONS: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression. PMID- 26557250 TI - Reference values for spirometry - report from the Obstructive Lung Disease in Northern Sweden studies. AB - BACKGROUND: Abnormal lung function is commonly identified by comparing observed spirometric values to corresponding reference values. It is recommended that such reference values for spirometry are evaluated and updated frequently. The aim of this study was to estimate new reference values for Swedish adults by fitting a multivariable regression model to a healthy non-smoking general population sample from northern Sweden. Further aims were to evaluate the external validity of the obtained reference values on a contemporary sample from south-western Sweden, and to compare them to the Global Lung Function Initiative (GLI) reference values. METHOD: Sex-specific multivariable linear regression models were fitted to the spirometric data of n=501 healthy non-smoking adults aged 22-91 years, with age and height as predictors. The models were extended to allow the scatter around the outcome variable to depend on age, and age-dependent spline functions were incorporated into the models to provide a smooth fit over the entire age range. Mean values and lower limits of normal, defined as the lower 5th percentiles, were derived. RESULT: This modelling approach resulted in unbiased estimates of the spirometric outcomes, and the obtained estimates were appropriate not only for the northern Sweden sample but also for the south-western Sweden sample. On average, the GLI reference values for forced expiratory volume in one second (FEV1) and, in particular, forced expiratory vital capacity (FVC) were lower than both the observed values and the new reference values, but higher for the FEV1/FVC ratio. CONCLUSION: The evaluation based on the sample of healthy non smokers from northern Sweden show that the Obstructive Lung Disease in Northern Sweden reference values are valid. Furthermore, the evaluation based on the south western Sweden sample indicates a high external validity. The comparison with GLI brought further evidence to the consensus that, when available, appropriate local population-specific reference values may be preferred. PMID- 26557251 TI - Diagnostic work-up in patients with possible asthma referred to a university hospital. AB - OBJECTIVE: The best strategy for diagnosing asthma remains unclear. Accordingly, the aim of this study was to evaluate diagnostic strategies in individuals with possible asthma referred to a respiratory outpatient clinic at a university hospital. METHODS: All individuals with symptoms suggestive of asthma referred over 12 months underwent spirometry, bronchodilator reversibility test, Peak expiratory flow rate (PEF) registration, and bronchial challenge test with methacholine and mannitol on three separate days. The results of these tests were compared against an asthma diagnosis based on symptoms, presence of atopy and baseline spirometry made by a panel of three independent respiratory specialists. RESULTS: Of the 190 individuals examined, 63% (n=122) were classified as having asthma. Reversibility to beta2-agonist had the lowest sensitivity of 13%, whereas airway hyperresponsiveness to methacholine had the highest (69%). In contrast, specificity was the highest for reversibility testing (93%), whereas methacholine had the lowest specificity (57%). The combination of reversibility, peak-flow variability, and methacholine yielded a cumulative sensitivity of 78%, albeit a specificity of 41%. In comparison, a combination of reversibility and mannitol resulted in a specificity of 82% and a sensitivity of 42%. CONCLUSION: In this real-life population, different diagnostic test combinations were required to achieve a high specificity for diagnosing asthma and a high sensitivity, respectively: Our findings suggest that the diagnostic test approach should be based on whether the aim is to exclude asthma (high sensitivity required) or confirm a diagnosis of asthma (high specificity required). PMID- 26557252 TI - Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons. AB - INTRODUCTION: Continuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma. OBJECTIVE: The objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients' regular medication. METHODS: This multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study. RESULTS: Data from 30 patients (mean age 28; range 8-70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months. CONCLUSIONS: The addition of TLA to the patients' regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma. PMID- 26557247 TI - Exploring the origins of asthma: Lessons from twin studies. AB - This thesis explores the contribution of twin studies, particularly those studies originating from the Danish Twin Registry, to the understanding of the aetiology of asthma. First, it is explored how twin studies have established the contribution of genetic and environmental factors to the variation in the susceptibility to asthma, and to the variation in several aspects of the clinical expression of the disease such as its age at onset, its symptomatology, its intermediate phenotypes, and its relationship with other atopic diseases. Next, it is explored how twin studies have corroborated theories explaining asthma's recent increase in prevalence, and last, how these fit with the explanations of the epidemiological trends in other common chronic diseases of modernity. PMID- 26557253 TI - Pharmacological treatment of idiopathic pulmonary fibrosis - preclinical and clinical studies of pirfenidone, nintedanib, and N-acetylcysteine. AB - Three recent clinical trials on the pharmacologic treatment of idiopathic pulmonary fibrosis (IPF) mark a new chapter in the management of patients suffering from this very severe fibrotic lung disease. This review article summarizes the published investigations on the preclinical studies of three novel IPF drugs, namely pirfenidone, nintedanib, and N-acetylcysteine (NAC). In addition, the study protocols, differences, and the main findings in the recent clinical trials of these pharmacological treatments are reviewed. The strategy for drug development and the timeline from the discovery to the clinical use have been very different in these regimens. Pirfenidone was discovered in 1976 but only recently received approval in most countries, and even now its exact mechanism of action is unknown. On the contrary, nintedanib (BIBF1120) was identified in large drug screening tests as a very specific inhibitor of certain tyrosine kinases, but no published data on preclinical tests existed until 2014. NAC, a mucolytic drug with an antioxidant mechanism of action was claimed to possess distinct antifibrotic properties in several experimental models but proved to be ineffective in a recent randomized placebo-controlled trial. At present, no curative treatment is available for IPF. A better understanding of the molecular mechanisms of IPF as well as relevant preclinical tests including animal models and in vitro experiments on human lung cells are needed to promote the development of therapeutic drugs. PMID- 26557254 TI - Idiopathic fibrotic lung disease at a university hospital setting: management and prognostic factors. AB - BACKGROUND: Idiopathic fibrosing interstitial pneumonia consists of many subtypes, most associated with a poor prognosis. The aim of the study was to evaluate diagnostic procedures and treatment as well as survival in patients with idiopathic fibrosing interstitial pneumonia. METHODS: This study comprised 175 patients with idiopathic fibrosing interstitial pneumonia (ICD 10 code J84) that had been diagnosed at Uppsala University Hospital, during 2005 to 2012. Patient records were reviewed concerning: gender, age, smoking, occupational exposure, comorbidities, procedures, lung function, and treatment. Information on survival and cause of death was collected. RESULTS: A total of 98% had been examined with computed tomography, 93% with spirometry, 49% with measurement of diffusion capacity, 48% with bronchoalveolar lavage, and 23% with lung biopsy. Prednisolone had been prescribed to 74% while N-acetylcysteine (NAC) and omeprazole were prescribed to 54%, respectively. Five-year survival was 46%. Mortality was associated with high age, low diffusion capacity, and the use of NAC. CONCLUSION: High age and a low diffusion capacity are related to shorter survival in idiopathic fibrosing interstitial pneumonia. We also unexpectedly found that the use of NAC was related to shorter survival. A relatively low proportion of the patients were examined with diffusion capacity measurement. Thus, there is a possibility to improve diagnostic procedures and thereby improve estimation of prognosis in fibrotic lung disease. PMID- 26557257 TI - Genetics of asthma: an introduction for the clinician. AB - Asthma runs in families, and children of asthmatic parents are at increased risk of asthma. Prediction of disease risk is pivotal for the clinician when counselling atopic families. However, this is not always an easy task bearing in mind the vast and ever-increasing knowledge about asthma genetics. The advent of new genotyping technologies has made it possible to sequence in great detail the human genome for asthma-associated variants, and accordingly, recent decades have witnessed an explosion in the number of rare and common variants associated with disease risk. This review presents an overview of methods and advances in asthma genetics in an attempt to help the clinician keep track of the most important knowledge in the field. PMID- 26557256 TI - High prevalence of rhinitis symptoms without allergic sensitization in Estonia and Finland. AB - OBJECTIVES: Allergic rhinitis and atopy are more common in urban than rural environments. Non-allergic rhinitis has not been studied to a great extent. We aimed to assess the relationship of rhinitis symptoms with different profiles of allergic sensitization, comparing this in rural and urban environments. METHODS: The study population consisted of population-based cohorts of adults aged 26-60 from Helsinki, Finland, and rural Saaremaa and urban Tallinn, Estonia. We compared the results of a structured interview and skin prick tests and assessed the risk factors for rhinitis. RESULTS: The prevalence of rhinitis symptoms with atopy was 32.7% in Helsinki, 20.8% in Tallinn, and 12.5% in Saaremaa (p<0.001). Rhinitis symptoms without atopy were found in 26.4%, 29.8%, and 29.3% (p=n.s.), respectively. In Helsinki, 87.3% of participants with atopy identified symptoms as allergic, compared to 57.0% in Tallinn and 47.5% in Saaremaa. Childhood in the countryside (OR 0.63), family history of allergic rhinitis (OR 1.89), and polysensitization (OR 15.99) were significantly associated with rhinitis symptoms with atopy in a multivariate logistic regression model. The most common sensitizers were pollens and animals in Helsinki and mites in Estonia. Exposure to environmental tobacco smoke (OR 1.50) and family history of allergic rhinitis (OR 1.70) were associated with rhinitis symptoms without atopy. CONCLUSION: Rhinitis symptoms without allergic sensitization were common in both Finland and Estonia and were associated with environmental tobacco smoke. Family history of allergic rhinitis predisposed to rhinitis symptoms irrespective of atopy status. PMID- 26557255 TI - Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic? AB - Bronchodilators are mainstay for the symptomatic treatment of chronic obstructive pulmonary disease (COPD) and the introduction of long-acting bronchodilators has led to an improvement in the maintenance treatment of this disease. Various clinical trials have evaluated the effects of fixed dose long-acting beta2 agonists (LABA)/long-acting anti-muscarinics (LAMA) combinations and documented greater improvements in spirometry but such improvements do not always translate to greater improvements in symptom scores or reduction in the rates of exacerbation compared with a single component drug. An analysis of whether this significantly greater change in spirometry with combination therapy is additive or synergistic was undertaken and is the subject of this review. Bronchodilators are not disease modifiers and whilst glucocorticosteroids have been shown to reduce rates of exacerbation in moderate to severe COPD, the increase risk of pneumonia and bone fractures is a motivation enough to warrant developing novel anti-inflammatory and disease-modifying drugs and with the expectation of positive outcomes. PMID- 26557258 TI - A retrospective pilot study of the use of a new algorithm to improve quality control in bronchodilator studies. AB - Reversibility testing is used to identify a positive or negative response to bronchodilators. Results from a reversibility test can not only support a diagnosis of asthma but can alter a patient's treatment plan, so its clinical importance should not be understated. With multiple guidelines published classifying a 'positive response' it becomes unclear on how to categorise certain individuals. This study looks into the discrepancies between the guidelines, and introduces a new algorithm to help clinicians. This retrospective pilot study was completed across four hospitals in South Wales. Data were collected from a total of 117 patients referred for a reversibility study during November 2013 and April 2014. An algorithm was created to improve flow-volume loop (FVL) quality control when assessing airways bronchodilation in symptomatic patients. Each patient result was placed through four major reversibility guidelines [British Thoracic Society (BTS), National Institute for Clinical Excellence (NICE), Association for Respiratory Technology Physiologists (ARTP) and Global Lung Initiative (GLI)] and the new algorithm. When comparing published guidelines, 75% of patients would receive the same bronchodilator response decision, positive or negative, irrespective of the guideline followed. Variability between the numbers of positive responders in each guideline varied by up to 58%, with NICE found to give the least number of positive responses (7%), and BTS giving the greatest (65%). Using the new algorithm, over one third (38%) of patients required a repeat FVL, as baseline and/or post-bronchodilator FVLs did not meet the quality control specification. Further investigation is needed to establish the clinical impact of the new algorithm, and its approach to using the whole of the FVL in bronchodilator analysis; however, quality control during reversibility testing needs to be improved to ensure that bronchodilator responses are correctly identified. PMID- 26557259 TI - Organisation of diagnosis and treatment of idiopathic pulmonary fibrosis and other interstitial lung diseases in the Nordic countries. AB - INTRODUCTION: Differences in the organisation of idiopathic pulmonary fibrosis (IPF) and interstitial lung diseases (ILDs) in the Nordic countries are not well described. Diagnostic setups, treatment modalities and follow-up plans may vary due to national, cultural and epidemiological features. The aim of the present study was to describe the different organisation of diagnostics and treatment of IPF and ILD in the Nordic countries. METHODS: All university and regional hospitals with respiratory physicians were invited to respond to a questionnaire collecting data on the number of physicians, nurses, patients with ILD/IPF, the presence of and adherence to disease-specific national and international guidelines, diagnosis and treatment including ILD-specific palliation and rehabilitation programmes. RESULTS: Twenty-four university and 22 regional hospitals returned the questionnaire. ILD and IPF incidence varied between 1.4 and 20/100,000 and 0.4 and 10/100,000, respectively. Denmark and Estonia have official national plans for the organisation of ILD. The majority of patients are managed at the university hospitals. The regional hospitals each manage 46 (5 200) patients with ILD and 10 (0-20) patients with IPF. There are from one to four ILD centres in each country with a median of two ILD specialists employed. Specialised ILD nurses are present in nine hospitals. None of the Nordic countries have national guidelines made by health authorities. The respiratory societies in Sweden, Norway and Denmark have developed national guidelines. All hospitals except two use the ATS/ERS/JRS/ALAT IPF guidelines from 2011. The limited number of ILD specialists, ILD-specialised radiologists and pathologists and the low volume of ILD centres were perceived as bottlenecks for implementation of guidelines. Twenty of the 24 university hospitals have multidisciplinary conferences (MDCs). Pulmonologists and radiologists take part in all MDCs while pathologists only participate at 17 hospitals. Prescription of pirfenidone is performed by all university hospitals except in Estonia. Triple therapy with steroid, azathioprine and N-acetylcysteine is not used. No hospitals have specific palliation programmes for patients with ILD/IPF, but 36 hospitals have the possibility of referring patients for palliative care, mostly based on existing oncology palliative care teams; seven hospitals have rehabilitation programmes for ILD. CONCLUSION: There are obvious differences between the organisations of ILD patients in the Nordic countries. We call for national plans that consider the challenge of cultural and geographical differences and suggest the establishment of national reference centres and satellite collaborative hospitals to enable development of common guidelines for diagnostics, therapy and palliation in this patient group. PMID- 26557260 TI - Rituximab-induced interstitial lung disease: five case reports. AB - Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association. PMID- 26557261 TI - Kinetics of TH2 biomarkers in sputum of asthmatics following inhaled allergen. AB - BACKGROUND: Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum. OBJECTIVES: To test whether allergen-induced TH2 inflammatory markers can be reproducibly quantified by sensitive detection techniques in ultracentrifuged sputum and the effect of fluticasone (FP) on these endpoints. METHODS: Thirteen allergic asthmatics with dual allergen-induced airway responses, documented during a single-blind placebo run-in period, participated in a double-blind, two period crossover study. Each period consisted of three consecutive days, separated by >=3 weeks. Following randomization, subjects inhaled FP (500 ug bid, five doses total) or placebo. On Day 2 in each study period, allergen challenge was performed and airway response measured by forced expiratory volume in 1 sec (FEV1) until 7 h post-challenge. Sputum was induced 24 h pre-allergen and 7 and 24 h post-allergen. Sputum samples were split into two portions: TH2 biomarkers were quantified by Meso Scale multiplex platform following ultracentrifugation, and cell differentials were counted on Giemsa-May-Grunwald-stained cytospins. Allergen-induced changes in inflammatory endpoints were compared between FP and placebo using a mixed model ANCOVA. RESULTS: Inhaled allergen induced dual airway responses in all subjects during both placebo periods with reproducible late asthmatic response (LAR) and increased sputum inflammatory biomarkers (IL-2, IL 4, IL-13, and eotaxin-1) and eosinophil counts. FP effectively blunted both the LAR and the inflammatory biomarkers. CONCLUSIONS: Combining novel, sensitive quantification methods with ultracentrifugation allows reproducible quantification of sputum biomarkers following allergen challenge, reversed by FP. This approach allows non-invasive identification of pharmacodynamic targets for anti-asthma therapies. PMID- 26557262 TI - Epidemiology and natural history of atopic diseases. AB - The atopic diseases - atopic dermatitis, asthma, and hay fever - pose a great burden to the individual and society, not least, since these diseases have reached epidemic proportions during the past decades in industrialized and, more recently, in developing countries. Whereas the prevalence of the atopic diseases now seems to have reached a plateau in many Western countries, they are still on the increase in the developing world. This emphasizes continuing research aimed at identifying the causes, risk factors, and natural history of these diseases. Herein, the fundamental aspects of the natural history and epidemiology of the atopic diseases are reviewed. PMID- 26557263 TI - Central arterial stiffness is increased among subjects with severe and very severe COPD: report from a population-based cohort study. AB - INTRODUCTION: Cardiovascular disease (CVD) is common in chronic obstructive pulmonary disease (COPD) and is, as productive cough, related to poorer prognosis in COPD. Central arterial stiffness is a marker of early atherosclerosis, but the association between COPD, productive cough, and arterial stiffness as a possible indicator of CVD is unclear. OBJECTIVES: To compare both arterial stiffness among subjects with and without COPD and the impact of productive cough in a population based cohort. METHODS: A population-based cohort, including 993 COPD and 993 non COPD subjects, has been invited to annual examination since 2005. In 2010, 947 subjects, of which 416 had COPD (according to the GOLD spirometric criteria), participated in examinations including structured interview, spirometry, and measurements of central arterial stiffness as pulse wave velocity (PWV). RESULTS: PWV was higher in GOLD 3-4 compared to non-COPD (10.52 vs. 9.13 m/s, p=0.042). CVD and age >=60 were both associated with significantly higher PWV in COPD as well as in non-COPD. In COPD, those with productive cough had higher PWV than those without, significantly so in GOLD 1 (9.59 vs. 8.92 m/s, p=0.024). In a multivariate model, GOLD 3-4 but not productive cough was associated with higher PWV, when adjusted for sex, age group, smoking habits, blood pressure, CVD, and pulse rate. CONCLUSIONS: GOLD 3-4, age >=60, and CVD were associated with increased arterial stiffness, and also increased in COPD subjects with productive cough compared to those without. Of importance, GOLD 3-4 but not productive cough remained associated with increased central arterial stiffness when adjusted for confounders. PMID- 26557264 TI - Outcomes of acute exacerbations in COPD in relation to pre-hospital oxygen therapy. AB - BACKGROUND: Pre-hospital, high-concentration oxygen therapy during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has been associated with increased mortality. Recent COPD guidelines have encouraged titrated oxygen therapy with a target saturation range of 88-92%. Oxygen therapy leading to saturation above 92% is defined as 'inappropriate oxygen therapy'. OBJECTIVES: To examine the frequency of inappropriate oxygen therapy and whether inappropriate oxygen therapy in the ambulance in an urban area with short transit time to hospital was associated with poor outcome. METHODS: In an audit of 405 consecutive patients with AECOPD arriving by ambulance to Hvidovre Hospital, details of transit time, oxygen administration, saturation, and arterial blood gases were registered. Outcomes were respiratory acidosis, need of supported ventilation, length of hospitalisation, and in-hospital mortality. RESULTS: Only 15 patients were not treated with oxygen and information on oxygen flow was missing in seven patients and on saturation on one patient. Altogether, 352 (88.7%) of 397 patients received inappropriate oxygen therapy. Patients on 'inappropriate oxygen therapy' (saturation >=92%) had a high frequency of respiratory acidosis at hospital admission, 108 (33.5%) of 324 patients, length of stay was on average 5.1 days, 12.5% of the patients needed ventilatory support, and in-hospital mortality was 3.4%. CONCLUSION: The majority of patients with AECOPD received inappropriate oxygen therapy in the ambulance, but their need of ventilatory support, length of stay, and mortality were low. Randomised studies are needed to clarify the optimal pre-hospital oxygen therapy. PMID- 26557265 TI - Ensemble Supervised Classification Method Using the Regions of Interest and Grey Level Co-Occurrence Matrices Features for Mammograms Data. AB - BACKGROUND: Breast cancer is one of the most encountered cancers in women. Detection and classification of the cancer into malignant or benign is one of the challenging fields of the pathology. OBJECTIVES: Our aim was to classify the mammogram data into normal and abnormal by ensemble classification method. PATIENTS AND METHODS: In this method, we first extract texture features from cancerous and normal breasts, using the Gray-Level Co-occurrence Matrices (GLCM) method. To obtain better results, we select a region of breast with high probability of cancer occurrence before feature extraction. After features extraction, we use the maximum difference method to select the features that have predominant difference between normal and abnormal data sets. Six selected features served as the classifying tool for classification purpose by the proposed ensemble supervised algorithm. For classification, the data were first classified by three supervised classifiers, and then by simple voting policy, we finalized the classification process. RESULTS: After classification with the ensemble supervised algorithm, the performance of the proposed method was evaluated by perfect test method, which gave the sensitivity and specificity of 96.66% and 97.50%, respectively. CONCLUSIONS: In this study, we proposed a new computer aided diagnostic tool for the detection and classification of breast cancer. The obtained results showed that the proposed method is more reliable in diagnostic to assist the radiologists in the detection of abnormal data and to improve the diagnostic accuracy. PMID- 26557266 TI - Giant Organized Hematoma Originating From the Inferior Turbinate. AB - We reported CT of a case of giant organized hematoma originating from the inferior turbinate without any paranasal sinuses involvement, with an emphasis on different patterns of enhancement of the tumor on enhanced CT scans. This case was exceptional because of unusual location and difficulties in diagnosis. Moreover, organized hematoma of nasal cavity should be considered in the differential diagnosis of a unilateral, huge and easy bleeding lesion in the nasal cavity. A high clinical suspicion based on endoscopic and radiologic findings plays an important role to make an accurate diagnosis. PMID- 26557267 TI - An Experimental Study to Determine the Role of Inferior Vena Cava Filter in Preventing Bone Cement Implantation Syndrome. AB - BACKGROUND: Inferior vena cava filters (IVCF) are frequently used for preventing pulmonary embolism (PE) following deep venous thromboembolism. OBJECTIVES: The present study was designed to investigate whether IVCF could prevent or impede the occurrence of bone cement implantation syndrome (BCIS), since PE is considered as the central mechanism of BCIS. MATERIALS AND METHODS: Fifteen sheep were divided into three groups: bone cement free (BCF) group, cement implantation (CI) group and IVCF group. In all the groups, an osteotomy proximal to the greater trochanter of left femur was carried out. In BCF group, the femoral canal was not reamed out or packed with any bone cement. In CI and IVCF groups, the left femoral canals were packed with bone cement, to simulate the cementing procedures carried out in hip replacement. An OptEase((r)) filter was placed and released in inferior vena cava, prior to packing cement in the femoral canal in IVCF group, while the IVCF was not released in the CI group. The BCF group was considered as control. RESULTS: Systolic blood pressure (SBP), saturation of oxygen (SaO2) and partial pressure of carbon dioxide (PaCO2) declined significantly 10 min after the bone cement packing, in CI group, compared to those in BCF group. This was accompanied by a rise in the arterial pH. However, IVCF prevented those changes in the CI group. On ultrasonography, there were dotted echoes in right atrium in the CI group, after bone cement packing, while such echoes were hardly seen in the IVCF group. CONCLUSION: This study demonstrates that IVCF could prevent BCIS effectively, and, as a corollary, suggests that PE represents the leading cause of the constellation of BCIS symptoms. PMID- 26557268 TI - Twin Reversed Arterial Perfusion (TRAP) Sequence; Characteristic Gray-Scale and Doppler Ultrasonography Findings. AB - Twin reversed arterial perfusion (TRAP) sequence is a syndrome with poor prognosis, seen only in monochorionic monozygotic twin pregnancies. The incidence is one in 35.000 births and one in 100 monozygotic twin pregnancies. It is characterized with a recipient fetus exhibiting lethal anomalies including acardia and a pump fetus. Mortality is usually due to heart failure or premature labor caused by polyhydramnios of pump fetus. Herein, we report a case of TRAP sequence that emphasizes the importance of gray-scale and color Doppler imaging in the diagnosis and management of TRAP sequence. PMID- 26557269 TI - Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging. AB - BACKGROUND: Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful. OBJECTIVES: The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors. PATIENTS AND METHODS: DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups. RESULTS: There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 +/- 1.29 and 0.90 +/- 0.70 (median +/- interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02). CONCLUSION: Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy. PMID- 26557270 TI - Inferior Epigastric Artery Pseudoaneurysm Following Paracentesis in a Liver Graft Recipient: A Case Report. AB - Pseudoaneurysm happens when the artery wall is injured and the blood is contained by the surrounding tissues with eventual formation of a fibrous sac communicating with the artery. We report a case of a 39-year-old man with inferior epigastric artery (IEA) pseudoaneurysm after paracentesis. The pseudoaneurysm was diagnosed by Doppler ultrasound and treated by surgical intervention regarding the patient's underlying comorbidity. IEA false aneurysm must be included in the differential diagnosis during investigation of the cause of any swelling after paracentesis. Cirrhotic patients may be more prone to this complication because of thin rectus muscle that could not confine the hematoma. PMID- 26557271 TI - Correlation of Shape and Size of Sella Turcica With the Type of Facial Skeletal Class in an Iranian Group. AB - BACKGROUND: In orthodontic science, diagnosis of facial skeletal type (class I, II, and III) is essential to make the correct treatment plan that is usually expensive and complicated. Sometimes results from analysis of lateral cephalometry radiographies are not enough to discriminate facial skeletal types. In this situation, knowledge about the relationship between the shape and size of the sella turcica and the type of facial skeletal class can help to make a more definitive decision for treatment plan. OBJECTIVES: The present study was designed to investigate this relationship in patients referred to a dental school in Iran. PATIENTS AND METHODS: In this descriptive-analytical study, cephalometric radiographies of 90 candidates for orthodontic treatment (44 females and 46 males) with an age range of 14 - 26 years and equal distribution in terms of class I, class II, and class III facial skeletal classification were selected. The shape, length, diameter, and depth of the sella turcica were determined on the radiographs. Linear dimensions were assessed by one-way analysis of variance while the correlation between the dimensions and age was investigated using Pearson's correlation coefficient. RESULTS: Sella turcica had normal morphology in 24.4% of the patients while irregularity (notching) in the posterior part of the dorsum sella was observed in 15.6%, double contour of sellar floor in 5.6%, sella turcica bridge in 23.3%, oblique anterior wall in 20% and pyramidal shape of the dorsum sella in 11.1% of the subjects. In total, 46.7% of class I patients had a normal shape of sella turcica, 23.3% of class II patients had an oblique anterior wall and a pyramidal shape of the dorsum sella, and 43.3% of class III individuals had sella turcica bridge (the greatest values). Sella turcica length was significantly greater in class III patients compared to class II and class I (P < 0.0001). However, depth and diameter of sella turcica were similar in class I, class II, and class III patients. Furthermore, age was significantly correlated to the diameter of sella turcica as greater diameters were observed in older ages (P < 0.04). CONCLUSION: A significant relationship exists between the type of facial skeletal classification and the shape of the sella turcica; as in class III patients, sella turcica bridge was reported with a higher frequency. Also, sella turcica had a significantly higher length in these patients than in those with class I and class II facial skeletal types. PMID- 26557272 TI - A Case of Complete Unroofed Coronary Sinus Syndrome Combined With Coronary Sinus Stenosis Leading to Asymptomatic Presentation. AB - We describe a patient with an asymptomatic complete unroofed coronary sinus (CS) syndrome associated with the CS stenosis in the absence of a persistent left superior vena cava (SVC) as identified on coronary computed tomography angiography. There was a large defect between the CS and the left atrium (i.e. a large left-to-right shunt), but an unusual combination of the absence of a persistent left SVC (i.e. no risk for brain abscess due to the absence of a right to-left shunt) and the CS stenosis (i.e. a markedly reduced degree of a left-to right shunt), resulting in an asymptomatic presentation. PMID- 26557273 TI - Developmental Venous Anomaly With Asymmetrical Basal Ganglia Calcification: Two Case Reports and Review of the Literature. AB - Developmental venous anomaly (DVA) is a common lesion formerly known as venous angioma. DVAs drain normal brain parenchyma; however, parenchymal abnormalities surrounding DVAs have been reported. Unilateral putamen and caudate calcification in the drainage territory of DVAs has so far been reported in 7 cases, all with deep venous drainage. We present two additional cases of DVAs, one with superficial and the other one with deep venous drainage, associated with basal ganglia calcifications. We emphasize that DVAs should be in the differential diagnosis of unilateral basal ganglia calcifications. PMID- 26557274 TI - Parapharyngeal Angiofibroma: A Case Report. AB - Nasopharyngeal angiofibroma is a relatively uncommon vascular tumor affecting adolescent males and it characteristically originates in the posterior lateral wall of the nasopharynx. Primary extra-nasopharyngeal angiofibroma is very rare. Here, I present a case of angiofibroma of the parapharyngeal space in a 53-year old woman with CT and sonographic findings. PMID- 26557275 TI - Retroperitoneal Cystic Malignant Fibrous Histiocytoma Mimicking a Psoas Abscess. AB - Primary neoplasms in the psoas muscle including schwannoma and soft tissue sarcoma with secondary cystic degeneration are rare entities. They are difficult to distinguish from psoas abscess purely based on radiological findings. Malignant fibrous histiocytoma (MFH) in the retroperitoneum is an uncommon entity in contrast to liposarcoma and leiomyosarcoma. Psoas abscess is a common infection in the retroperitoneum, especially in regions where tuberculosis is endemic. In the current case, the patient presented with gradually progressive lower abdominal pain and raised erythrocyte sedimentation rate (ESR), lymphocyte count and sputum positive for acid fast bacilli. There was a presence of previous history of skeletal tuberculosis. Imaging revealed well-defined multilocular cystic lesion involving the left psoas muscle which along with the clinical scenario suggested psoas abscess. However, post-operative biopsy showed the lesion to be a MFH with extensive cystic degeneration. To the best of our knowledge, cystic MFH mimicking an abscess has been previously reported only once in an oncology literature. PMID- 26557276 TI - Myocardial Metabolic Abnormality in a Primary Left Atrial Rhabdomyosarcoma: Localized 1H MR Spectroscopy. AB - We report a 73-year-old woman with primary left atrial rhabdomyosarcoma and its 1H MR spectroscopy (MRS) findings. The tumor showed a 2.8 cm sized lesion in the posteroinferior atrial wall on MRI. 1H MR spectra were acquired using a point resolved spectroscopy (PRESS) sequence with electrocardiographic (ECG) gating and respiratory motion. The use of 1H-MRS allowed the quantification of triglyceride (TG) peak groups at 0.9 and 1.3 ppm, and unsaturated group of lipids at 2.1 ppm, creatine (Cr) at 3.0 ppm, and choline (Cho) at 3.2 ppm. The percentages of the myocardial metabolites based on water-peak in the interventricular septum were TG 18.4%, Cr 1.6%, Cho 3.3% and unsaturated group 4.0%, whereas the rhabdomyosarcoma showed TG 118.8%, unsaturated group 5.1%, Cr 1.3%, Cho 3.5% and the olefinic components of fatty acid at 5.4 ppm 24.5%. This case demonstrates that 1H-MRS is potentially useful to diagnose the rhabdomyosarcoma by quantifying the myocardial metabolites which are important biomarkers for heart function and diseases. PMID- 26557277 TI - Fluoroscopic Analysis of Tibial Translation in Anterior Cruciate Ligament Injured Knees With and Without Bracing During Forward Lunge. AB - BACKGROUND: Despite several studies with different methods, the effect of functional knee braces on knee joint kinematics is not clear. Direct visualization of joint components through medical imaging modalities may provide the clinicians with more useful information. OBJECTIVES: In this study, for the first time in the literature, video fluoroscopy was used to investigate the effect of knee bracing on the sagittal plane kinematics of anterior cruciate ligament (ACL) injured patients. PATIENTS AND METHODS: For twelve male unilateral ACL deficient subjects, the anterior tibial translation was measured during lunge exercise in non-braced and braced conditions. Fluoroscopic images were acquired from the subjects using a digital fluoroscopy system with a rate of 10 fps. The image of each frame was scaled using a calibration coin and analyzed in AutoCAD environment. The angle between the two lines, tangent to the posterior cortexes of the femoral and tibial shafts was measured as the flexion angle. For the fluoroscopic images associated with 0 degrees , 15 degrees , 30 degrees , 45 degrees and 60 degrees knee flexion angles, the relative anterior-posterior configuration of the tibiofemoral joint was assessed by measuring the position of landmarks on the tibia and femur. RESULTS: Results indicated that the overall anterior translations of the tibia during the eccentric (down) and concentric (up) phases of lunge exercise were 10.4 +/- 1.7 mm and 9.0 +/- 2.2 mm for non braced, and 10.1 +/- 3.4 mm and 7.4 +/- 2.5 mm, for braced conditions, respectively. The difference of the tibial anterior-posterior translation behaviors of the braced and non-braced knees was not statistically significant. CONCLUSION: Fluoroscopic imaging provides an effective tool to measure the dynamic behavior of the knee joint in the sagittal plane and within the limitations of this study, the pure mechanical stabilizing effect of functional knee bracing is not sufficient to control the anterior tibial translation of the ACL deficient patients during lunge exercise. PMID- 26557278 TI - Barber Pole Sign in CT Angiography, Adult Presentation of Midgut Malrotation: A Case Report. AB - Adult midgut volvulus is a challenging diagnosis because of its low incidence and nonspecific symptoms. Diagnostic delay and long-term complaints are frequent in this clinical scenario. We reported a patient referred to our diagnostic imaging unit with intermittent abdominal pain, bloating and episodic vomiting for several years. He underwent barium gastrointestinal transit and abdominal ultrasound, which revealed severe gastric dilatation, food retention and slow transit until a depressed duodenojejunal flexure, with malrotation of the midgut and jejunal loops being located in the right upper quadrant. Computed tomography angiography was performed, showing rotation of the small intestine around the mesentery root, suggestive of midgut malrotation. In addition, an abnormal twisted disposition of superior mesenteric artery with corkscrew appearance was seen, shaping the pole barber sign which was evident in volume rendering three-dimensional reconstructions. The patient underwent scheduled surgical treatment without any complication and had good outcome after hospital discharge and follow-up. Computed tomography plays an important role in evaluation of adult midgut volvulus. In addition, angiographic reconstructions can help us to assess the anatomic disposition of mesenteric vascular supply. Both of these assessments are useful in preoperative management. PMID- 26557279 TI - Comparing the Effect of Different Voxel Resolutions for Assessment of Vertical Root Fracture of Permanent Teeth. AB - BACKGROUND: The teeth with undiagnosed vertical root fractures (VRFs) are likely to receive endodontic treatment or retreatment, leading to frustration and inappropriate endodontic therapies. Moreover, many cases of VRFs cannot be diagnosed definitively until the extraction of tooth. OBJECTIVES: This study aimed to assess the use of different voxel resolutions of two different cone beam computerized tomography (CBCT) units in the detection VRFs in vitro. MATERIALS AND METHODS: The study material comprised 74 extracted human mandibular single rooted premolar teeth without root fractures that had not undergone any root canal treatment. Images were obtained by two different CBCT units. Four image sets were obtained as follows: 1) 3D Accuitomo 170, 4 * 4 cm field of view (FOV) (0.080 mm(3)); 2) 3D Accuitomo 170. 6 * 6 cm FOV (0.125 mm(3)); 3) NewTom 3G, 6" (0.16 mm(3)) and 4) NewTom 3G, 9" FOV (0.25 mm(3)). Kappa coefficients were calculated to assess both intra- and inter-observer agreements for each image set. RESULTS: No significant differences were found among observers or voxel sizes, with high average Z (Az) results being reported for all groups. Both intra and inter-observer agreement values were relatively better for 3D Accuitomo 170 images than the images from NewTom 3G. The highest Az and kappa values were obtained with 3D Accuitomo 170, 4 * 4 cm FOV (0.080 mm(3)) images. CONCLUSION: No significant differences were found among observers or voxel sizes, with high Az results reported for all groups. PMID- 26557280 TI - In Vivo Evaluation of Feeding Arteries of Tumors in Dorsal Sector of the Liver. AB - BACKGROUND: The identification of the dorsal sector of the liver and its detailed vascular anatomy is of primary importance for surgical practice and segmental transcatheter arterial chemoembolization. OBJECTIVES: This study aimed to investigate the feeding arteries of tumors in dorsal sector of the liver. PATIENTS AND METHODS: Computed tomography (CT) and digital subtraction angiography (DSA) images of eleven patients with tumors of the dorsal sector of the liver were analyzed retrospectively. The hepatic arteries that probably supplied the tumors were observed in DSA images. The case number of each hepatic artery feeding to the tumors was calculated. A scoring method was used to estimate each hepatic artery contribution to the tumor stain in DSA images. The accumulative scores were employed to evaluate the blood supply of feeding arteries of the tumors. RESULTS: The data of the study revealed that right posterior hepatic artery (RPHA) (n = 9), middle hepatic artery (MHA) (n = 8), left medial hepatic artery (LMHA) (n = 6), right anterior hepatic artery (RAHA) (n = 5), and caudate hepatic artery (CaHA) (n = 3) were the feeding arteries of the tumors in dorsal sector in eleven patients. The accumulative scores of RPHA, MHA, RAHA, and LMHA were 23, 17, 11, and 7 points, respectively (chi(2) = 6.827, P = 0.078, Friedman test). The total scores of right hepatic artery (RHA) branches and left hepatic artery (LHA) branches were 51 and 11 points, respectively (Z = -2.764, P = 0.006, Wilcoxon rank test). CONCLUSION: The RPHA, MHA, RAHA, and LMHA might be the main feeding arteries of the tumors in dorsal sector of the liver. PMID- 26557281 TI - Fluoroscopy Guided Transurethral Placement of Ureteral Metallic Stents. AB - Ureteral stent exchange is usually performed under both fluoroscopic and cystoscopic guidance. We experienced two cases with retrograde placement of metallic ureteral stent via urethra under fluoroscopic guidance. When patients with double-J ureteral stent (DJUS)have symptom and want to change DJUS to metallic stent, fluoroscopic guided transurethral placement of ureteral metallic stent is a good option as alternative of cystoscopic procedure or percutaneous procedure through percutaneous nephrostomy tract. PMID- 26557282 TI - Computed Tomography Pulmonary Angiography for Evaluation of Patients With Suspected Pulmonary Embolism: Use or Overuse. AB - BACKGROUND: The use of computed tomography pulmonary angiography (CTPA) has been increased during the last decade. OBJECTIVES: We studied the adherence to current diagnostic recommendations for evaluation of pulmonary embolism in a teaching hospital of Tehran University of Medical Sciences. PATIENTS AND METHODS: The registered medical records (Wells scores and serum D-dimer level) of all patients whose CTPA was performed with suspicion of pulmonary thromboembolism (PTE) were studied retrospectively. Modified Wells score of each patient was determined without being aware of the CTPA results. The patients were categorized to those with a high (likely) clinical probability (score > 4) and low (unlikely) clinical probability (score<= 4) of PTE. RESULTS: During a 6-month period, 82 patients who underwent CTPA were included. The prevalence of PTE was 62.2% in the group of subjects with a likely clinical risk. In 45 (54.8%) of those patients whose CTPA was requested, the PTE was unlikely based on modified Wells criteria. In the clinically unlikely group, serum D-dimer assay was done in 15 out of 45 (33.3%), while it was inappropriately checked in 10 out of 37 (27.0%) with a clinically likely risk. General adherence rate to diagnostic algorithm of PTE was 43.9%. CONCLUSION: There is still excessive unjustified concern of PTE in less trained physicians leading to excessive diagnostic work-up. Loyalty to the existing guideline for management of suspected PTE in educational hospitals and supervision of attending physicians could prevent overuse of CTPA. PMID- 26557283 TI - Desmoplastic Fibroma, Report of a Rare Case in Infraorbital Rim. AB - Desmoplastic fibroma (DF) is a rare and locally aggressive intraosseous tumor with unknown etiology. The mandible is the common site of involvement in the maxillofacial region. However, it is believed that DF can arise in any bone of the body. A wide age distribution has been reported for DF occurrence, extending from birth to the sixth decade of life, with a peak incidence at 10 to 19 years of age. In this study, diagnostic and therapeutic management of a 6-year-old girl with a desmoplastic fibroma of the inferior orbital rim and zygomatic buttress are discussed. Cone beam computed tomography (CBCT) revealed a mixed lesion in infraorbital rim, which had ill-defined borders and a straight thick bony septum inside the lesion. It also involved the zygomatic process of maxilla and zygomatic bone. According to radiologic concepts, this rare lesion may mimic fibro-osseous, benign and especially malignant lesions. Regarding different treatment plans, identification of this lesion is essential. Furthermore, presence of coarse and irregular or straight septa along with some imaging criteria for malignant lesions such as destruction of the cortex, periosteal reaction and soft tissue invasion would be helpful to differentiate this lesion from malignant and multilocular benign lesions. PMID- 26557284 TI - Prevalence of osteoporosis and its association with serum vitamin D level in older people in Amirkola, North of Iran. AB - BACKGROUND: Ageing of population worldwide will be responsible for a major increase of the incidence of osteoporosis in elderly. For the individual, osteoporotic fractures result in great disability as well as loss of quality of life and also represent an enormous burden for healthcare systems. This study was conducted to determine the prevalence of osteoporosis and its association with serum vitamin D level in elderly people in Amirkola, North of Iran. METHODS: In this cross-sectional study, 193 subjects aged 60 years old and over were assessed in Amirkola. Using a standard questionnaire, individual characteristics and densitometry (with DXA) results were collected and the data were analyzed with SPSS, chi square tests and linear regression. RESULTS: The overall prevalence rate of osteoporosis was 32.1% in at least one measurement sites (28.5% in lumbar and 14.5% in femoral region), while 49.7% of elderly people suffering from decreased bone mass (osteopenia). Osteoporosis prevalence in women was 55.7% and this value in elderly men was 12.4%. Bone mineral density has negative association with age in femoral region (p<0.01, r-0.3), but no statistical relationships were seen between bone mineral density and serum 25-hydroxy vitamin D level in this study. CONCLUSION: Our findings revealed higher prevalence of osteoporosis in elderly people especially in women compared to other studies in Iran, and also showed high prevalence rate of vitamin D deficiency. No relationships were found between serum vitamin D and bone density in this study. PMID- 26557285 TI - Bone mineral density changes during treatment of rheumatoid arthritis with disease-modifying-anti-rheumatic drugs. AB - BACKGROUND: Bone mineral density (BMD) changes during the course of rheumatoid arthritis (RA). The present study was designed to investigate the status of BMD in patients with RA treated with anti-rheumatic drugs. METHODS: BMD at the femoral neck (FN-BMD) and lumbar spine (LS-BMD) were measured by dual energy x ray absorptiometry (DXA) method using Norland densitometer. Disease activity (DA) was assessed by calculation of DAS28 score. The patients with at least twice BMD measurements were included and those who received treatment for osteoporosis were excluded. The mean FN-BMD and LS-BMD changes from baseline between the two BMD measurements was determined. RESULTS: Nineteen patients (17 females, 2 males) with the mean age of 54.5+/-7.7 years, with mean disease duration of 141.8+/-58 months were treated for an average period of 2.9+/-1.9 years. All the patients were treated with low-dose methotrexate (MTX) up to 15 mg/week alone or with combination of hydroxychloroquine and/or sulfasalazine and 5 mg prednisolone daily. At the end of study period, the value of FN-BMD gr/cm2 decreased by - 4.24% (p=0.12) and LS-BMD gr/cm2 by - 6.57% (p=0.009). The mean FN BMD Z-score increased by +7.66% (p=0.64) and LS-BMD Z-score decreased by - 14.7% (p=0.120). CONCLUSION: The findings of this study indicate that bone loss in RA continues despite anti-inflammatory treatment. The lower rate of bone loss from FN compared with LS may be attributed to suppression of hip synovitis with anti-inflammatory treatment. PMID- 26557286 TI - Efficacy of levothyroxine on benign thyroid nodule. AB - BACKGROUND: Suppressive therapy with levothyroxine for reducing the size of thyroid nodules has not been really accepted. The purpose of this study was to assess the effect of levothyroxine on the size of benign thyroid nodules. METHODS: Forty patients with confirmed benign nodule were randomly divided into two groups. Group I received 50g/day levothyroxine for six months but group II did not take it. Sonography was used to measure the dimensions of nodules before and after six months. TSH serum levels were measured before and after treatment. This clinical trial study was registered as IRCT 201103185692 N3. The data were collected and analyzed. RESULTS: The mean age of levothyroxine group was 41.57+/ 9.41 and control group was 44.45+/-10.9 years (p=0.386). The TSH levels and longitudinal and transverse dimensions in both groups were similar (p>0.05). The TSH levels before and after treatment were 2+/-1.65 and 0.52+/-0.67 mUI/L (p=0.001). The Longitudinal and transverse dimensions before and after treatment in case group were 1.9+/-1.11, 1.90+/-1.15 and 1.44+/-0.90, 1.49+/-1.02 cm respectively (p=0.74, p=0.7, respectively) but in control group, were 2.19+/ 1.32, 1.97+/-1.4 and 1.57+/-0.95, 1.26+/-0.7, respectively (p=0.35 and 0.1, respectively). CONCLUSION: The results show that suppressive therapy with levothyroxine lead no alteration in the size of benign nodules. PMID- 26557287 TI - How is total antioxidant status in plasma of Patients with brucellosis? AB - BACKGROUND: Brucella species can cause infection in a wide range of animals and human beings. Oxidative events against brucella infection are not well elucidated. It is possible that brucellosis may be related to increased free radical production and antioxidant depletion. Thus, the aim of this study was to determine the total antioxidant capacity (TAC) before and after treatment of patients with brucellosis. METHODS: In the present study, a total of 48 patients with brucellosis, 23 males and 25 females, were detected through Wright >=1/160 2ME >=1/80, in association with compatible clinical findings. All patients were treated with standard regimens of therapy. Total antioxidant capacity (TAC) was determined with ferric reducing antioxidant power (FRAP) using spectrophotometric method before and after treatment. RESULTS: TAC levels were significantly lower in pre-treatment than in post-treatment patients, 0.783+/-0.015 and 0.819+/-0.024 m mol/L respectively (p<0.01). There was not significant relation between plasma TAC levels and age or gender of the patients. CONCLUSION: TAC may be useful as an early marker of oxidative stress to monitor and optimize antioxidant therapy as an adjunct in the management of patients with brucellosis. PMID- 26557288 TI - Evaluation of guide wire cannulation in reduced risk of post - ERCP pancreatitis and facilitated bile duct cannulation. AB - BACKGROUND: Pancreatitis is most common complication of post-ERCP and needs to admission at least for one day. The purpose of this study was to assess the efficacy of guide wire for better common bile duct (CBD) cannulation for reducing post-ERCP pancreatitis. METHODS: From April 2010 through March 2011, the patients who needed ERCP and referred to Shahid Beheshti and Rouhani Teaching Hospital were entered into the study. Guide wire cannulation (65 subjects) as case group and 78 cases with standard cannulation as control group were performed on them randomly. Data from these cases were collected and analyzed. RESULTS: One hundred eighteen (82.5%) patients were females and 28 (17.5%) were males. The mean age of these patients was 56.5+/-16.8 years. Post- ERCP pancreatitis rate in guide wire group was 6 (9.2%) and in the standard group was 12 (15.4%) (p=0.269). Successful cannulation in these two groups was 67.7% and 67.9%, respectively (p=0.974). CONCLUSION: The results show that post- ERCP pancreatitis rate in both groups are similar. Other studies with large number of cases are required to confirm our results. PMID- 26557289 TI - Prevalence of asthma, allergic rhinitis and eczema in elementary schools in Sari (Iran). AB - BACKGROUND: Allergic diseases including asthma, allergic rhinitis (AR) and eczema are common chronic diseases in children. The purpose of this study was to determine the prevalence of asthma, AR and eczema in Sari, Iran. METHODS: This study was carried out on all elementary schools selected as a cluster from February 2010 to July 2010 in Sari, North of Iran. A questionnaire was provided according to International Study of Asthma and Allergies in Childhood (ISAAC) protocol. Asthma, AR, eczema and their combinations were recorded. RESULTS: Out of the 1818 cases, 646 (35%) subjects had allergic disorder; 223 (12%) had asthma, 318 (17%) had AR and 105 (6%) had eczema The prevalence of allergic disorder in boys (65%) was higher than the girls (40%) (p<0.05). CONCLUSION: The results show that around one - third of the elementary school children have allergic disorders. The prevalence in males is higher than the females. PMID- 26557290 TI - Epidemiological, clinical and laboratory features of patients hospitalized with 2009 pandemic influenza in north of Iran. AB - BACKGROUND: The clinical manifestations and outcome of influenza infection differ between various patients in the world. The purpose of this study was to assess the clinical manifestations of patients with confirmed or suspected novel H1N1 flu infection in Sari, North of Iran. METHODS: From September 2009 to January 2010, the patients' data were collected by retrospective chart review of medical records. Laboratory confirmation included a positive RT-PCR (reverse transcriptase-polymerase-chain-reaction assay) from a nasal or pharyngeal swab sample. RESULTS: Nearly 80% of established patients were in age group of 15-45 years. Approximately 14.6% of female cases were pregnant There was no significant difference in clinical and laboratory characteristics of patients with confirmed H1N1 virus infection to total cases with Influenza Like Illness (ILI). Thirty nine (95.1%) of the established patients had a combination of fever plus sore throat or cough. Relative lymphopenia was reported in 36.6%. Pneumonia was the most common complication. Acute pericarditis evolved in one case and aseptic meningitis was reported in another. CONCLUSION: Precise collecting information of clinical manifestations, risk factors and other characteristics of flu, can help to the early infection detection, timely treatment of patients and proper preventive measurements. PMID- 26557291 TI - Can serum procalcitonin measurement help monitor the treatment of acute bacterial meningitis? A prospective study. AB - BACKGROUND: Previous studies have demonstrated the value of serum procalcitonin (PCT) as a marker of bacterial infection, as well as the rapid decrease in its concentration with appropriate antibiotic treatment. The aim of this study was to determine the variation in serum PCT levels over time during the treatment of acute bacterial meningitis (ABM) in adults. METHODS: In this prospective analytical study, 36 acute meningitis patients (26 males and 10 females) with mean age of 38.4+/-20.1 years were studied. Among them, 17 patients with fever and neck stiffness and CSF profiles consistence, ABM was treated by appropriate antibiotic regimen. We measured PCT serum levels before and after 24 and 72 hours after initiation of treatment. Decrease in the body temperature and feeling of well being were the clinical criteria for treatment response. The data were collected and analyzed. RESULTS: Serum level of PCT in the beginning of treatment, 24 and 72 hours after initiation of treatment was 2.58+/-4.62, 2.50+/ 4.6 and 1.52+/-3.03 ng/ml, respectively. Difference in PCT initially and 24 h later was 0.044+/-0.08 (p=0.025) and after 72 h was 1.74+/-2.92 (p=0.013). The mean of PCT level was greater in patients not improving (5.34+/-4.42 vs. 2.08+/ 3.46). CONCLUSION: Although decreasing PCT was low in 24 h after treatment, this decrement is more significant after 72 h. PCT serum level may be used as a follow up of treatment response in ABM. PMID- 26557293 TI - Laryngeal tuberculosis without pulmonary involvement. AB - BACKGROUND: Tuberculosis of the larynx is a rare form of tuberculosis. Patients usually present with hoarseness or dysphagia and other nonspecific constitutional symptoms like fever or localized pain. In this study, we present a case of primary vocal cord lesion with tuberculosis. CASE PRESENTATION: A 72 year old man presented with hoarseness of voice, low grade fever, and night sweating with in three month duration. Laryncoscopic study showed unilateral thickening of vocal cord and biopsy of the lesion showed granuloma with caseous necrosis. Chest x-ray was normal. The patient was treated with standard regimen of tuberculosis and was cured after 6 months of therapy. CONCLUSION: Laryngeal tuberculosis should be considered in the differential diagnosis of patients with hoarseness without pulmonary involvement in endemic regions of tuberculosis. PMID- 26557292 TI - Role of oxidative stress in pathogenesis of metabolic syndrome. AB - The metabolic syndrome (MS) recognized as a major cause of type 2 diabetes and cardiovascular diseases, has become one of the major public health challenges worldwide. The pathogenesis of the metabolic syndrome is multiple and still poorly understood. No single factor has yet been identified as an underlying causal factor. There is a growing belief, however, that obesity, especially visceral obesity, may play an important role in the development of the syndrome. Visceral adiposity seems to be an independent predictor of insulin sensitivity, impaired glucose tolerance, dyslipidemia and elevated blood pressure. An increasing number of studies confirm that oxidative stress, chronic inflammation and angiogenesis all play important roles in the pathogenesis of MS. Chronic hyperglycemia causes oxidative stress in tissues prone to complications in patients with diabetes. Oxidative stress occurs in a cellular system when the production of free radical moieties exceeds the antioxidant capacity of that system. If cellular antioxidants do not remove free radicals, radicals attack and damage proteins, lipids, and nucleic acids. The oxidized or nitrosylated products of free radical attack have decreased biological activity, leading to loss of energy metabolism, cell signaling, transport, and other major functions. These altered products are also targeted for proteosome degradation, further decreasing cellular function. Accumulation of such injury ultimately leads a cell to die through necrotic or apoptotic mechanisms. In conclusion, a puzzle of many pieces of evidence suggests that free radical overgeneration may be considered the key in the generation of insulin resistance, diabetes, and cardiovascular disease. PMID- 26557294 TI - How Age Affects Auditory-Cognitive Interactions in Speech Comprehension. AB - To participate effectively in multi-talker conversations, listeners need to do more than simply recognize and repeat speech. They have to keep track of who said what, extract the meaning of each utterance, store it in memory for future use, integrate the incoming information with what each conversational participant has said in the past, and draw on the listener's own knowledge of the topic under consideration to extract general themes and formulate responses. In other words, to acquire and use the information contained in spoken language requires the smooth and rapid functioning of an integrated system of perceptual and cognitive processes. Here we review evidence indicating that the operation of this integrated system of perceptual and cognitive processes is more easily disrupted in older than in younger adults, especially when there are competing sounds in the auditory scene. PMID- 26557295 TI - Age-Related Changes in Auditory and Cognitive Abilities in Elderly Persons with Hearing Aids Fitted at the Initial Stages of Hearing Loss. AB - In this study, we investigated the relation between the use of hearing aids at the initial stages of hearing loss and age-related changes in the auditory and cognitive abilities of elderly persons. 12 healthy elderly persons participated in an annual auditory and cognitive longitudinal examination for three years. According to their hearing level, they were divided into 3 subgroups - the normal hearing group, the hearing loss without hearing aids group, and the hearing loss with hearing aids group. All the subjects underwent 4 tests: pure-tone audiometry, syllable intelligibility test, dichotic listening test (DLT), and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Short Forms. Comparison between the 3 groups revealed that the hearing loss without hearing aids group showed the lowest scores for the performance tasks, in contrast to the hearing level and intelligibility results. The other groups showed no significant difference in the WAIS-R subtests. This result indicates that prescription of a hearing aid during the early stages of hearing loss is related to the retention of cognitive abilities in such elderly people. However, there were no statistical significant correlations between the auditory and cognitive tasks. PMID- 26557296 TI - Screening for Otologic Functional Impairments in the Elderly: Whose Job is it Anyway? AB - Among the most prevalent of chronic conditions affecting older adults globally, hearing loss prevalence is increasing and its impact on society growing. Untreated hearing loss diminishes ones ability to communicate and its strong association with depression and cognitive decline adds further to the burden of hearing loss. Hearing health care is rarely included in the traditional medical exam for older adults, it is typically not considered a risk factor for cognitive decline or falls, and it is not a condition for which routine screening has been recommended by the U.S. Preventive Services Task Force. Yet in older adults, disability typically results from many small risks acting together with different people having a different pattern of multifactorial risk (U.S. Preventive Services Task Force, 2010). The importance of preventive hearing health care in primary care is discussed along with a screening strategy with targeted interventions designed to target older at risk adults. PMID- 26557297 TI - SUN-test (Speech Understanding in Noise): A Method for Hearing Disability Screening. AB - The SUN-test (Speech Understanding in Noise) is a speech-in-noise test to screen adults and older adults for hearing disability. The SUN-test consists in a short list of intervocalic consonants (VCV, vowel-consonant-vowel) in noise that are presented in a three-alternatives forced choice (3AFC) paradigm by means of a touch-screen interface. Based on the number of stimuli correctly identified, the tested subject gets one of three possible test outcomes: no listening difficulties, a hearing check would be advisable, or a hearing check is recommended. This paper reviews the main results obtained with the SUN-test in the Italian language in a population of nearly 1,300 adults and older adults with varying degrees of audiometric thresholds and audio-metric configurations, tested both in low and in high ambient noise settings. Results obtained in the tested population revealed that the outcomes of the SUN-test were in line with the outcomes of pure-tone testing, and that the test performance was similar both in low and in high ambient noise (up to 65 dB A). Results obtained with the SUN-test were not biased by the age of the subject because the performance of younger and older subjects in the test was similar. The mean duration of the SUN-test was nearly 40 s/ear, and was lower than 1 minute per ear even in subjects older than 80 years so that both ears could be tested, on average, in 2 minutes. The SUN test was considered easy or slightly difficult by nearly 90% of subjects; test duration was judged short or fair by nearly 95% of subjects, and the overall evaluation of the test was pleasant, or neutral, in more than 90% of subjects. Overall, results of this study indicated that the SUN-test might be feasible for application in adult hearing screening. The test is fast, easy, self convincing, and reflects differences in hearing sensitivity between the tested subjects. The outcomes of the SUN-test were not influenced by the noise level in the test room (up to 65 dB A) indicating that the test, as such, might be feasible to screen adults and older adults both in clinical and in non clinical settings, such as convenient care clinics, hearing aid providers, or pharmacies, where the ambient noise is, typically, not controlled. PMID- 26557298 TI - e-Health Technologies for Adult Hearing Screening. AB - The development of hearing diagnosis methods and hearing screening methods are not isolated phenomena: they are intimately related to changes in the cultural background and to advances in fields of medicine and engineering. In the recent years, there has been a rapid evolution in the development of fast, easy and reliable techniques for low-cost hearing screening initiatives. Since adults and elderly people typically experience a reduced hearing ability in challenging listening situations [e.g., in background noise, in reverberation, or with competing speech (Pichora-Fuller & Souza, 2003)], these newly developed screening tests mainly rely on the recognition of speech stimuli in noise, so that the real experienced listening difficulties can be effectively targeted (Killion & Niquette, 2000). New tests based on the recognition of speech in noise are being developed on portable, battery-operated devices (see, for example, Paglialonga et al., 2011), or distributed diffusely using information and communication technologies. The evolutions of e-Health and telemedicine have shifted focus from patients coming to the hearing clinic for hearing health evaluation towards the possibility of evaluating the hearing status remotely at home. So far, two ways of distributing the hearing test have primarily been used: ordinary telephone networks (excluding mobile networks) and the internet. When using the telephone network for hearing screening, the predominantly test is a speech-in-noise test often referred to as the digit triplet test where the subjects hearing status is evaluated as the speech-to-noise threshold for spoken digits. This test is today available in some ten countries in Europe, North America and Australia. The use of internet as testing platform allows several different types of hearing assessment tests such as questionnaires, different types of speech in noise tests, temporal gap detection, sound localization (minimum audible angle), and spectral (un)masking tests. Also, the use of the internet allows audiovisual presentations as well as visual interaction and cues in the tests for a more ecological approach. Even if several new and novel approaches for hearing assessment using the internet are surfacing, the validated tests are based on questionnaires or speech-in-noise. Although the internet allows for a broader flora of pure auditory and audiovisual tests for hearing health assessment, calibration problems such as timing uncertainty, output levels and modes of presentation (speakers or earphones) limits the usability at present. PMID- 26557299 TI - Hearing Impairment in Dementia - How to Reconcile Two Intertwined Challenges in Diagnostic Screening. PMID- 26557300 TI - An Economic Model of Adult Hearing Screening. PMID- 26557301 TI - Pilot Initiatives of Adult Hearing Screening in Italy. AB - A series of pilot initiatives of adult hearing screening programs were organized in eight large and small-size cities in Italy in the past two years. The screening initiatives were held in public places, supermarkets, drugstores, and in some universities of the third age, and involved an overall population of 2,278 screened subjects with age ranging from 13 to 93 years. Three different screening tests were used to assess hearing ability in the participants, i.e.: screening pure tone audiometry (PTA), an automated speech-in-noise screening test (the SUN-test), and a screening questionnaire of self-perceived hearing handicap (the HHIE-S). This paper describes the organization and management of these screening initiatives and reviews the main results obtained in the screened population, using the three different screening tests. Results obtained in these pilot initiatives showed that screening adults for hearing problems might be feasible, on a local level, in non clinical settings and can be performed quite easily with the support of local coordinators and partners, such as associations or local authorities. It is recognized that further initiatives and studies will have to be performed to better define the key aspects related to the organization and management of adult hearing screening programs, either at a local, regional, or national level. PMID- 26557302 TI - Adult Hearing Screening: The Cyprus Pilot Program. PMID- 26557303 TI - Screening Among Workers in a Dockyard in the City of Varna. PMID- 26557304 TI - A 16-year Longitudinal Study of Hearing in very Old Australians. PMID- 26557305 TI - Strategies of Adult Hearing Aid Selection. PMID- 26557306 TI - Interventions after Screening for Hearing Difficulties: A Retrospective Investigation of Interventions other than Hearing Aids. PMID- 26557307 TI - Testing Listening Effort for Speech Comprehension Using the Individuals' Cognitive Spare Capacity. PMID- 26557308 TI - Experiences with Bimodal Hearing and Bilateral Cochlear Implantation in the Elderly. PMID- 26557309 TI - The NAL-NL2 Prescription Procedure. PMID- 26557310 TI - Systematic Review of Barriers and Facilitators to Hearing Aid Uptake in Older Adults. PMID- 26557311 TI - Perceptions about Hearing Aids from Elderly Non-Users: A Bicultural Point of View (Italy and USA). PMID- 26557312 TI - A Representative Study of Hearing Ability in North West Germany. PMID- 26557313 TI - Auditory Temporal Processing and Aging: Implications for Speech Understanding of Older People. PMID- 26557315 TI - Auditory Temporal Processes in the Elderly. AB - Several studies have reported age-related decline in auditory temporal resolution and in working memory. However, earlier studies did not provide evidence as to whether these declines reflect overall changes in the same mechanisms, or reflect age-related changes in two independent mechanisms. In the current study we examined whether the age-related decline in auditory temporal resolution and in working memory would remain significant even after controlling for their shared variance. Eighty-two participants, aged 21-82 performed the dichotic temporal order judgment task and the backward digit span task. The findings indicate that age-related decline in auditory temporal resolution and in working memory are two independent processes. PMID- 26557314 TI - Stimulus-Onset-Asynchrony as the Main Cue in Temporal Order Judgment. PMID- 26557316 TI - Contribution of Resolved and Unresolved Harmonic Regions to Brainstem Speech Evoked Responses in Quiet and in Background Noise. AB - Speech auditory brainstem responses (speech ABR) reflect activity that is phase locked to the harmonics of the fundamental frequency (F0) up to at least the first formant (F1). Recent evidence suggests that responses at F0 in the presence of noise are more robust than responses at F1, and are also dissociated in some learning-impaired children. Peripheral auditory processing can be broadly divided into resolved and unresolved harmonic regions. This study investigates the contribution of these two regions to the speech ABR, and their susceptibility to noise. We recorded, in quiet and in background white noise, evoked responses in twelve normal hearing adults in response to three variants of a synthetic vowel: i) Allformants, which contains all first three formants, ii) F1Only, which is dominated by resolved harmonics, and iii) F2&F3Only, which is dominated by unresolved harmonics. There were no statistically significant differences in the response at F0 due to the three variants of the stimulus in quiet, nor did the noise affect this response with the Allformants and F1Only variants. On the other hand, the response at F0 with the F2&F3Only variant was significantly weaker in noise than with the two other variants (p<0.001). With the response at F1, there was no difference with the Allformants and F1Only variants in quiet, but was expectedly weaker with the F2&F3Only variant (p<0.01). The addition of noise significantly weakened the response at F1 with the F1Only variant (p<0.05), but this weakening only tended towards significance with the Allformants variant (p=0.07). The results of this study indicate that resolved and unresolved harmonics are processed in different but interacting pathways that converge in the upper brainstem. The results also support earlier work on the differential susceptibility of responses at F0 and F1 to added noise. PMID- 26557317 TI - Audiological Screening in People with Diabetes. First Results. PMID- 26557319 TI - Editorial. PMID- 26557318 TI - Hearing Ability and its Relationship with Psychosocial Health, Work-Related Variables, and Health Care Use: The National Longitudinal Study on Hearing. PMID- 26557321 TI - Simultaneous Vibrant Soundbridge Implantation and 2nd Stage Auricular Reconstruction for Microtia with Aural Atresia. AB - Aural atresia and severe microtia are associated malformations that result in problems with hearing and cosmesis, associated speech and language difficulties and diminished self-esteem. In cases where middle ear ossiculoplasty and aural atresia canalplasty are expected to give poor hearing outcomes that would eventually require the use of hearing aids, bone anchored hearing aids or active middle ear implants may be better options. This case report describes a simultaneous Vibrant Soundbridge implantation and 2(nd) stage auricular reconstruction with rib graft cartilage for an 11-year-old boy with grade III microtia and aural atresia 8 months after the 1(st) stage reconstruction. Audiometric results of the Vibrant Soundbridge aided ear were comparable to that of the contralateral hearing aid aided ear. PMID- 26557320 TI - Spectrum Resolving Power of Hearing: Measurements, Baselines, and Influence of Maskers. AB - Contemporary methods of measurement of frequency resolving power in the auditory system are reviewed. Majority of classical methods are based on the frequency selective masking paradigm and require multi-point measurements (a number of masked thresholds should be measured to obtain a single frequency-tuning estimate). Therefore, they are rarely used for practical needs. As an alternative approach, frequency-selective properties of the auditory system may be investigated using probes with complex frequency spectrum patterns, in particular, rippled noise that is characterized by a spectrum with periodically alternating maxima and minima. The maximal ripple density discriminated by the auditory system is a convenient measure of the spectrum resolving power (SRP). To find the highest resolvable ripple density, a phase-reversal test has been suggested. Using this technique, normal SRP, its dependence on probe center frequency, spectrum contrast, and probe level were measured. The results were not entirely predictable by frequency-tuning data obtained by masking methods. SRP is influenced by maskers, with on- and off-frequency maskers influencing SRP very differently. Dichotic separation of the probe and masker results in almost complete release of SRP from influence of maskers. PMID- 26557322 TI - Distortion-Product Otoacoustic Emissions: Body Position Effects with Simultaneous Presentation of Tone Pairs. AB - This study examined the effect of three different body positions on distortion product otoacoustic emission (DPOAE) amplitude and noise levels with multiple primary tone pairs simultaneously-presented to 36 normal-hearing female human adults. Other studies have demonstrated that the simultaneously presented tone pairs method shows clinical promise as a screener, but the sequential method remains in widespread clinical use. Postural changes have been suggested to have an effect not only on DPOAEs, but also transient-evoked OAEs and stimulus frequency OAEs. DPOAE amplitude and noise levels were recorded in seated, supine, and side-lying positions to the following order of simultaneously-presented tone pairs relative to the f2 frequencies: 1187, 2375, and 4812 Hz; 1500, 3000, and 6062 Hz; and 1875, 3812, and 7625 Hz. No DPOAE could be detected reliably at 7625 Hz as result of poor signal-to-noise ratio. For remaining DPOAEs, statistical analyses revealed that amplitudes were not significantly different among the three body positions. However, at 1500 Hz and below, body position did have a statistically significant effect on noise levels though they are likely clinically negligible. Except at 7625 Hz, results suggest that DPOAEs recorded using a simultaneously presented tone pairs appear to be comparably recorded regardless of an individual's body position. PMID- 26557323 TI - Speech Perception in Noise in Normally Hearing Children: Does Binaural Frequency Modulated Fitting Provide More Benefit than Monaural Frequency Modulated Fitting? AB - The aim of the present study was to compare the benefit of monaural versus binaural ear-level frequency modulated (FM) fitting on speech perception in noise in children with normal hearing. Reception threshold for sentences (RTS) was measured in no-FM, monaural FM, and binaural FM conditions in 22 normally developing children with bilateral normal hearing, aged 8 to 9 years old. Data were gathered using the Pediatric Malay Hearing in Noise Test (P-MyHINT) with speech presented from front and multi-talker babble presented from 90 degrees , 180 degrees , 270 degrees azimuths in a sound treated booth. The results revealed that the use of either monaural or binaural ear level FM receivers provided significantly better mean RTSs than the no-FM condition (P<0.001). However, binaural FM did not produce a significantly greater benefit in mean RTS than monaural fitting. The benefit of binaural over monaural FM varies across individuals; while binaural fitting provided better RTSs in about 50% of study subjects, there were those in whom binaural fitting resulted in either deterioration or no additional improvement compared to monaural FM fitting. The present study suggests that the use of monaural ear-level FM receivers in children with normal hearing might provide similar benefit as binaural use. Individual subjects' variations of binaural FM benefit over monaural FM suggests that the decision to employ monaural or binaural fitting should be individualized. It should be noted however, that the current study recruits typically developing normal hearing children. Future studies involving normal hearing children with high risk of having difficulty listening in noise is indicated to see if similar findings are obtained. PMID- 26557324 TI - Development of Spanish Version of the Littlears Parental Questionnaire for Use in the United States and Latin America. AB - The LittlEARS Auditory Questionnaire is a parent questionnaire created to assess development of age-dependent auditory behaviors of children in the pre-verbal stage. The original questionnaire was developed in Austria (in German), and is now being introduced in the United States in English. This study was designed to obtain normative data on a Spanish translation. Fifty parents or caregivers participated. Responses were obtained at their child's visit to a hospital clinic or an external ambulatory site. Children ranged in age from .5 to 21.4 months (mean = 9.5 months). Parents were either Spanish monolingual or bilingual representing 5 national origins. Analyses included correlation of age with total score, and with individual questions, index of difficulty, discrimination and selectivity indices, scale analysis, split-half reliability and internal consistency. Specifically, correlation between age and number of observed behaviors was 0.927. A measure of internal consistency was high, 0.95. Results indicated that the translated LittlEARS for use with Spanish speakers is a potentially useful tool for clinicians assessing pre-verbal auditory behavior. High correlations of total score with age suggested that the questionnaire reflects a progression of auditory skills in the 0 to 24 months age group. PMID- 26557325 TI - Influence of postconceptional age on universal newborn hearing screening in NICU babies. AB - The feasibility of universal newborn hearing screening (UNHS) using automated auditory brainstem response (AABR) devices in the neonatal intensive care unit (NICU) is already well demonstrated. The aim of this study was to find out whether the postconceptional age (PCA) of the babies at the time of the AABR measurement has an influence on the measuring results and to determine the earliest time point for a reliable hearing screening in preterm neonates. Hearing screening measurements of 634 neonates (NICU-Babies) were included. We had complete data for 577 of these babies. The babies were born between 24 and 42 weeks of gestation in the years 2007-2008 and were screened in the Neonatal Unit of the Marburg University hospital. In this group, the hearing screening had been performed at or after 32 weeks of PCA. The AABR measurements showed a specificity of 93.9% (babies tested between 32 and 34 weeks of PCA), 95.8% (tested between 35 and 37 weeks), 95.9% (tested between 38 and 40 weeks of PCA) and 92.1% (tested after 40 weeks of PCA). Hearing screening yields reliable results at 32 weeks PCA. Therefore, an UNHS can be already performed before term without risking a higher rate of false positive results. However, individual factors such as cardiorespiratory and temperature stability of the baby should be considered. PMID- 26557326 TI - Is there addiction to loud music? Findings in a group of non-professional pop/rock musicians. AB - Listening to loud music may be connected to addictive behavior possibly leading to damaging effects on the cochlea. We hypothesized that members of non professional pop/rock bands with regular exposure to loud music are more likely to show an addictive-like behavior for loud music than matched control subjects. Fifty non-professional musicians and 50 matched control subjects were asked to complete the Northeastern Music Listening Survey (NEMLS) with two basic components. The first comprises an adaptation of the validated Michigan Alcohol Screening Test (MAST) to study the addictive-like behavior towards loud music. The second comprises the criteria outlined by the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Society for the diagnosis of substance dependence. The NEMLS was scored using the same point system as used in the MAST. The DSM-IV criteria for substance dependence were met by nine of the musician group and by one control subject. Seven of these nine musicians also had a positive NEMLS score. Traits of addictive-like behavior to loud music were detected more often in members of nonprofessional pop/rock bands than in control subjects. PMID- 26557327 TI - Indication criteria for cochlear implants and hearing aids: impact of audiological and non-audiological findings. AB - Owing to technological progress and a growing body of clinical experience, indication criteria for cochlear implants (CI) are being extended to less severe hearing impairments. It is, therefore, worth reconsidering these indication criteria by introducing novel testing procedures. The diagnostic evidence collected will be evaluated. The investigation includes postlingually deafened adults seeking a CI. Prior to surgery, speech perception tests [Freiburg Speech Test and Oldenburg sentence (OLSA) test] were performed unaided and aided using the Oldenburg Master Hearing Aid (MHA) system. Linguistic skills were assessed with the visual Text Reception Threshold (TRT) test, and general state of health, socio-economic status (SES) and subjective hearing were evaluated through questionnaires. After surgery, the speech tests were repeated aided with a CI. To date, 97 complete data sets are available for evaluation. Statistical analyses showed significant correlations between postsurgical speech reception threshold (SRT) measured with the adaptive OLSA test and pre-surgical data such as the TRT test (r=-0.29), SES (r=-0.22) and (if available) aided SRT (r=0.53). The results suggest that new measures and setups such as the TRT test, SES and speech perception with the MHA provide valuable extra information regarding indication for CI. PMID- 26557328 TI - Sensitivity of cortical auditory evoked potential detection for hearing-impaired infants in response to short speech sounds. AB - Cortical auditory evoked potentials (CAEPs) are an emerging tool for hearing aid fitting evaluation in young children who cannot provide reliable behavioral feedback. It is therefore useful to determine the relationship between the sensation level of speech sounds and the detection sensitivity of CAEPs, which is the ratio between the number of detections and the sum of detections and non detections. Twenty-five sensorineurally hearing impaired infants with an age range of 8 to 30 months were tested once, 18 aided and 7 unaided. First, behavioral thresholds of speech stimuli /m/, /g/, and /t/ were determined using visual reinforcement orientation audiometry. Afterwards, the same speech stimuli were presented at 55, 65, and 75 dB sound pressure level, and CAEPs were recorded. An automatic statistical detection paradigm was used for CAEP detection. For sensation levels above 0, 10, and 20 dB respectively, detection sensitivities were equal to 72+/-10, 75+/-10, and 78+/-12%. In 79% of the cases, automatic detection P-values became smaller when the sensation level was increased by 10 dB. The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound for infants with sensorineural hearing loss. The detection of a CAEP might provide confidence, to a degree commensurate with the detection probability, that the infant is detecting that sound at the level presented. When testing infants where the audibility of speech sounds has not been established behaviorally, the lack of a cortical response indicates the possibility, but by no means a certainty, that the sensation level is 10 dB or less. PMID- 26557329 TI - Effect of stimuli, transducers and gender on acoustic change complex. AB - The objective of this study was to investigate the effect of stimuli, transducers and gender on the latency and amplitude of acoustic change complex (ACC). ACC is a multiple overlapping P1-N1-P2 complex reflecting acoustic changes across the entire stimulus. Fifteen males and 15 females, in the age range of 18 to 25 (mean=21.67) years, having normal hearing participated in the study. The ACC was recorded using the vertical montage. The naturally produced stimuli /sa/ and /si/ were presented through the insert earphone/loud speaker to record the ACC. The ACC obtained from different stimuli presented through different transducers from male/female participants were analyzed using mixed analysis of variance. Dependent t-test and independent t-test were performed when indicated. There was a significant difference in latency of 2N1 at the transition, with latency for /sa/ being earlier; but not at the onset portions of ACC. There was no significant difference in amplitude of ACC between the stimuli. Among the transducers, there was no significant difference in latency and amplitude of ACC, for both /sa/ and /si/ stimuli. Female participants showed earlier latency for 2N1 and larger amplitude of N1 and 2P2 than male participants, which was significant. ACC provides important insight in detecting the subtle spectral changes in each stimulus. Among the transducers, no difference in ACC was noted as the spectra of stimuli delivered were within the frequency response of the transducers. The earlier 2N1 latency and larger N1 and 2P2 amplitudes noticed in female participants could be due to smaller head circumference. The findings of this study will be useful in determining the capacity of the auditory pathway in detecting subtle spectral changes in the stimulus at the level of the auditory cortex. PMID- 26557330 TI - Efficacy of the LiSN & Learn auditory training software: randomized blinded controlled study. AB - Children with a spatial processing disorder (SPD) require a more favorable signal to-noise ratio in the classroom because they have difficulty perceiving sound source location cues. Previous research has shown that a novel training program - LiSN & Learn - employing spatialized sound, overcomes this deficit. Here we investigate whether improvements in spatial processing ability are specific to the LiSN & Learn training program. Participants were ten children (aged between 6;0 [years;months] and 9;9) with normal peripheral hearing who were diagnosed as having SPD using the Listening in Spatialized Noise - Sentences test (LiSN-S). In a blinded controlled study, the participants were randomly allocated to train with either the LiSN & Learn or another auditory training program - Earobics - for approximately 15 min per day for twelve weeks. There was a significant improvement post-training on the conditions of the LiSN-S that evaluate spatial processing ability for the LiSN & Learn group (P=0.03 to 0.0008, eta(2)=0.75 to 0.95, n=5), but not for the Earobics group (P=0.5 to 0.7, eta(2)=0.1 to 0.04, n=5). Results from questionnaires completed by the participants and their parents and teachers revealed improvements in real-world listening performance post training were greater in the LiSN & Learn group than the Earobics group. LiSN & Learn training improved binaural processing ability in children with SPD, enhancing their ability to understand speech in noise. Exposure to non spatialized auditory training does not produce similar outcomes, emphasizing the importance of deficit-specific remediation. PMID- 26557331 TI - Intratympanic injection of dexamethasone for treatment of tinnitus in patients with sudden sensorineural hearing loss. AB - The purpose of this study is to test the effectiveness of intratympanic dexamethasone injections as a treatment for severe tinnitus in idiopathic sudden sensorineural hearing loss (SNHL). We studied 37 patients who received intratympanic dexamethasone injections and 14 control patients who did not receive it, with severe tinnitus after onset of unilateral sudden SNHL. Hearing level did not change during this study in any patient. The relationship between the duration of tinnitus and effectiveness of treatment was investigated in sudden SNHL. We used a visual analogue scale to evaluate 51 patients with severe tinnitus at the stage of stable hearing level after idiopathic sudden sensorineural hearing loss. Forty-one per cent of patients showed significant improvement after treatment. The average period between onset of sudden sensorineural hearing loss and initiation of intratympanic dexamethasone injection was significantly shorter (207 days) in the improved group than in the unchanged group (482 days) (P<0.001). In control group, one of 14 patients presented significant improvement spontaneously. Intratympanic dexamethasone treatment may be effective in treatment of severe tinnitus after sudden SNHL at the stage of stable hearing level, and the shorter the period from onset of sudden deafness to the start of intratympanic dexamethasone treatment, the greater the improvement in tinnitus that can be expected. PMID- 26557332 TI - Comparison of auditory brainstem response peak measures using ear lobe, mastoid, and custom ear canal reference electrodes. AB - Auditory brainstem response (ABR) peak measures were compared for a custom ear canal electrode and traditional mastoid and ear lobe reference electrode sites with the assumption that the ear canal electrode would yield larger Wave I amplitudes. In this study, Waves I, III, and V latencies and amplitudes were measured and compared in twenty participants between the ages of 18 and 50, with particular interest in a potential Wave I advantage using the custom ear canal reference electrode. The statistical analysis suggested that all reference electrode sites yielded comparable results with no statistical differences in peak latency or peak-to-trough amplitude for Waves I, III, and V. Although the custom ear canal electrode did not produce larger Wave I amplitudes over the other two references, a deeper placement of the ear canal electrode might have yielded different results. PMID- 26557333 TI - Health behavior change in hearing healthcare: a discussion paper. AB - Health behavior change (HBC) refers to facilitating changes to habits and/or behavior related to health. In healthcare practice, it is quite common that the interactions between practitioner and patient involve conversations related to HBC. This could be mainly in relation to the practitioner trying to directly persuade the patients to make some changes in their health behavior. However, the patients may not be motivated to do so as they do not see this change as important. For this reason, direct persuasion may result in a breakdown of communication. In such instances, alternative approaches and means of indirect persuasion, such as empowering the patient and their family members, could be helpful. Furthermore, there are several models and/or theories proposed which explain the health behavior and also provide a structured framework for health behavior change. Many such models/approaches have been proven effective in facilitating HBC and health promotion in areas such as cessation of smoking, weight loss and so on. This paper provides an overview of main models/theories related to HBC and some insights into how these models/approaches could be adapted to facilitate behavior change in hearing healthcare, mainly in relation to: i) hearing help-seeking and hearing-aid uptake; and ii) hearing conservation in relation to music-induced hearing loss (MIHL). In addition, elements of current research related to this area and future directions are highlighted. PMID- 26557334 TI - Comparison of speech intelligibility measures for an electronic amplifying earmuff and an identical passive attenuation device. AB - The purpose of this study was to identify any differences between speech intelligibility measures obtained with MineEars electronic earmuffs (ProEars, Westcliffe, CO, USA) and the Bilsom model 847 (Sperian Hearing Protection, San Diego, CA, USA), which is a conventional passive-attenuation earmuff. These two devices are closely related, since the MineEars device consisted of a Bilsom 847 earmuff with the addition of electronic amplification circuits. Intelligibility scores were obtained by conducting listening tests with 15 normal-hearing human subject volunteers wearing the earmuffs. The primary research objective was to determine whether speech understanding differs between the passive earmuffs and the electronic earmuffs (with the volume control set at three different positions) in a background of 90 dB(A) continuous noise. As expected, results showed that speech intelligibility increased with higher speech-to-noise ratios; however, the electronic earmuff with the volume control set at full-on performed worse than when it was set to off or the lowest on setting. This finding suggests that the maximum volume control setting for these electronic earmuffs may not provide any benefits in terms of increased speech intelligibility in the background noise condition that was tested. Other volume control settings would need to be evaluated for their ability to produce higher speech intelligibility scores. Additionally, since an extensive electro-acoustic evaluation of the electronic earmuff was not performed as a part of this study, the exact cause of the reduced intelligibility scores at full volume remains unknown. PMID- 26557335 TI - Listening levels of teenage iPod users: does measurement approach matter? AB - The main objective of this study was to determine the influence of background noise levels and measurement approach on user-selected listening levels (USLLs) chosen by teenaged MP3 player users. It was hypothesized that the presence of background noise would (i) increase the USLL across all measurement approaches, (ii) result in no significant USLL differences between survey reports, objective lab measures or calibrated self-report field measures, and (iii) cause no interaction effect between level of background noise and measurement approach. There were two independent variables in this study: the level of background noise and measurement approach. The first independent variable, level of background noise, had two levels: quiet and transportation noise. The second independent variable, measurement approach, had three levels: survey, objective in-ear lab measurement and calibrated self-report field measurement. The dependent variable was ear canal A-weighted sound pressure level (dBA SPL). A 2 * 3 repeated measures ANOVA was used to determine the significance of the main and interaction effects. USLLs increased in the presence of background noise, regardless of the measurement approach used. However, the listening levels estimated by the participants using the survey and self-report field measure were significantly lower than those recorded using in-ear laboratory measurements by 9.6 and 3.3 dBA respectively. In-ear laboratory measures yielded the highest listening levels. Higher listening levels were observed in the presence of background noise for all measurement approaches. It appears that subjects' survey responses underestimate true listening levels in comparison to self-report calibrated field measures, and that both underestimate listening levels measured in the laboratory setting. More research in this area is warranted to determine whether measurement techniques can be refined and adjusted to accurately reflect real-world listening preferences. PMID- 26557336 TI - Notched-noise embedded frequency specific chirps for objective audiometry using auditory brainstem responses. AB - It has been shown recently that chirp-evoked auditory brainstem responses (ABRs) show better performance than click stimulations, especially at low intensity levels. In this paper we present the development, test, and evaluation of a series of notched-noise embedded frequency specific chirps. ABRs were collected in healthy young control subjects using the developed stimuli. Results of the analysis of the corresponding ABRs using a time-scale phase synchronization stability (PSS) measure are also reported. The resultant wave V amplitude and latency measures showed a similar behavior as for values reported in literature. The PSS of frequency specific chirp-evoked ABRs reflected the presence of the wave V for all stimulation intensities. The scales that resulted in higher PSS are in line with previous findings, where ABRs evoked by broadband chirps were analyzed, and which stated that low frequency channels are better for the recognition and analysis of chirp-evoked ABRs. We conclude that the development and test of the series of notched-noise embedded frequency specific chirps allowed the assessment of frequency specific ABRs, showing an identifiable wave V for different intensity levels. Future work may include the development of a faster automatic recognition scheme for these frequency specific ABRs. PMID- 26557337 TI - A report of extended high frequency audiometry thresholds in school-age children with no hearing complaints. AB - The aim of the study was to establish the extended high frequency thresholds (EHF) of school-age children with no hearing complaints. The study was conducted on 50 children aged 8 to 12 years with pure tone thresholds (0.5, 1 and 2 kHz) of 15 dB HL or less, with normal speech discrimination and tympanometry and with the presence of contralateral acoustic reflexes of 0.5, 1, 2 and 4 kHz. The children were tested for EHF at frequencies of 9, 10, 11.2, 12.5, 14 and 16 kHz. No significant differences were found between the right and left ear for female and male groups. The results allowed us to group the children into a single sample with mean thresholds (dB) of 8.6 (9 kHz), 6.2 (10 kHz), 8.2 (11.2 kHz), 7.1 (12.5 kHz), 0.4 (14 kHz), and -3.6 (16 kHz). We conclude that, for school-age children, the extended EHF below 15 dBHL could be used as an indication of normal hearing sensitivity. PMID- 26557338 TI - Characteristics of multiple sclerosis patient stance control disorders, measured by means of posturography and related to brainstem lesions. AB - Balance disorders are commonly observed during the course of multiple sclerosis (MS). The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke's Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel) in four conditions: eyes open and eyes closed standing on a firm surface and on a foam pad. Clinical and/or magnetic resonance imaging evidence of brainstem involvement was observed in 55.3% of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the 0-0.1 Hz and 0.1-0.25 Hz frequency bands. In conclusion, MS leads to pervasive postural disturbances in the majority of subjects, including the visuo vestibular loops and proprioception involving vestibulo-spinal pathways in at least 55.3% of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions. PMID- 26557339 TI - Evaluation of Speech Intelligibility and Sound Localization Abilities with Hearing Aids Using Binaural Wireless Technology. AB - Wireless synchronization of the digital signal processing (DSP) features between two hearing aids in a bilateral hearing aid fitting is a fairly new technology. This technology is expected to preserve the differences in time and intensity between the two ears by co-ordinating the bilateral DSP features such as multichannel compression, noise reduction, and adaptive directionality. The purpose of this study was to evaluate the benefits of wireless communication as implemented in two commercially available hearing aids. More specifically, this study measured speech intelligibility and sound localization abilities of normal hearing and hearing impaired listeners using bilateral hearing aids with wireless synchronization of multichannel Wide Dynamic Range Compression (WDRC). Twenty subjects participated; 8 had normal hearing and 12 had bilaterally symmetrical sensorineural hearing loss. Each individual completed the Hearing in Noise Test (HINT) and a sound localization test with two types of stimuli. No specific benefit from wireless WDRC synchronization was observed for the HINT; however, hearing impaired listeners had better localization with the wireless synchronization. Binaural wireless technology in hearing aids may improve localization abilities although the possible effect appears to be small at the initial fitting. With adaptation, the hearing aids with synchronized signal processing may lead to an improvement in localization and speech intelligibility. Further research is required to demonstrate the effect of adaptation to the hearing aids with synchronized signal processing on different aspects of auditory performance. PMID- 26557340 TI - Are Open-Fit Hearing Aids a Possible Alternative to Bone-Anchored Hearing Devices in Patients with Mild to Severe Hearing Loss? A Preliminary Trial. AB - Open-fit hearing aids (OFHAs) may be of benefit for some individuals with chronic outer and middle ear conditions for which boneanchored hearing devices (BAHDs) are normally recommended. The purpose of this study was to compare performance between OFHAs and BAHDs. A Starkey Destiny 800 OFHA was fit on eight adult BAHD users and speech perception measures in quiet and in background noise were compared under two different test conditions: i) BAHD only and ii) OFHA only. Equivalent outcome measure performance between these two conditions suggests that the OFHA was able to provide sufficient amplification for mild to moderate degrees of hearing loss (pure-tone averages (PTAs) less than 47 dB HL). The improved speech perception performances and increased loudness ratings observed for several of the participants with moderately-severe to severe degrees of hearing loss (PTAs of 47 dB HL or greater) in the BAHD only condition suggest that the OFHA did not provide sufficient amplification for these individuals. Therefore, OFHAs may be a successful alternative to the BAHD for individuals with no more than a moderate conductive hearing loss who are unable or unwilling to undergo implant surgery or unable to wear conventional hearing aids due to allergies, irritation, or chronic infection associated with the ear being blocked with a shell or earmold. PMID- 26557341 TI - Effects of Stimulus Intensity on Low-Frequency Toneburst Cochlear Microphonic Waveforms. AB - This study investigates changes in amplitude and delays in low-frequency toneburst cochlear microphonic (CM) waveforms recorded at the ear canal in response to different stimulus intensities. Ten volunteers aged 20-30 were recruited. Low-frequency CM waveforms at 500 Hz in response to a 14-ms toneburst were recorded from an ear canal electrode using electrocochleography techniques. The data was statistically analyzed in order to confirm whether the differences were significant in the effects of stimulus intensity on the amplitudes and delays of the low-frequency CM waveforms. Electromagnetic interference artifacts can jeopardize CM measurements but such artifacts can be avoided. The CM waveforms can be recorded at the ear canal in response to a toneburst which is longer than that used in ABR measurements. The CM waveforms thus recorded are robust, and the amplitude of CM waveforms is intensity-dependent. In contrast, the delay of CM waveforms is intensity-independent, which is different from neural responses as their delay or latency is intensity-dependent. These findings may be useful for development of the application of CM measurement as a supplementary approach to otoacoustic emission (OAE) measurement in the clinic which is severely affected by background acoustic noise. The development of the application in the assessment of low-frequency cochlear function may become possible if a further series of studies can verify the feasibility, but it is not meant to be a substitute for audiometry or OAE measurements. The measurement of detection threshold of CM waveform responses using growth function approach may become possible in the clinic. The intensity-independent nature of CMs with regards to delay measurements may also become an impacting factor for differential diagnoses and for designing new research studies. PMID- 26557342 TI - Cervical and Ocular Vestibular Evoked Myogenic Potentials Test Results in Individuals with Auditory Neuropathy Spectrum Disorders. AB - Auditory neuropathy spectrum disorder is a clinical disorder where the outer hair cell functioning is intact but the functioning of the auditory nerve is affected. Since, the 8(th) nerve is constituted by both the auditory and vestibular branch of nerve fibers, there are chances that the vestibular nerve might also be affected. Hence, the current study was carried out in order to determine the functioning of vestibular nerve in individuals with auditory neuropathy. A total of 11 participants were considered for the current study. Cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) were administered using the conventional protocol. In all the participants (100%) the oVEMPs were absent whereas in 20 ears out of 22 ears tested (90.90%) the cVEMPs were absent. The results of the present study indicate a high incidence of vestibular involvement in individuals with auditory neuropathy spectrum disorders. Also, it necessitates the inclusion of vestibular tests in the test battery used to assess individuals with auditory neuropathy spectrum disorder. PMID- 26557343 TI - Evaluation of the Hearing Aid Rehabilitation Questionnaire in Dutch: Examination of its Psychometric Properties and Potential Use as a Screening Instrument. AB - Items pertaining to hearing and hearing aids from the Hearing Aid Rehabilitation Questionnaire were applied to a heterogeneous sample of Dutch patients aged 55 years and more to evaluate their potential use in hearing screening. Subjects aged 55+ were recruited from a large general practitioners practice to participate. Three groups were formed: a group of 63 persons with a hearing aid, a group of 64 without a hearing aid but with sufficient hearing impairment to qualify for hearing aid reimbursement, and a group of 85 non-hearing impaired persons. Factor and reliability analyses revealed a structure with two scales regarding hearing, namely functionality and social hearing and three scales pertaining to hearing aids, namely hearing aid stigma, pressure to be assessed and not wanting a hearing aid. Scale validity was assessed with pure tone averages over the frequencies 1, 2 and 4 kHz and with a visual analogue scale for subjective hearing. The derived scales can be applied reliably in audiological assessment in an adult hearing screen setting to detect experienced hearing problems as well as attitudes related to hearing and hearing aids. PMID- 26557344 TI - Comparison of Cervical and Ocular Vestibular Evoked Myogenic Potentials in Dancers and Non-Dancers. AB - The objective of the study was to assess the sacculocollic and otolith ocular pathway function using cervical vestibular evoked myogenic potentials (cVEMP) and ocular vestibular myogenic potentials (oVEMP) in dancers and non dancers. Total 16 subjects participated in the study. Out of 16 participants, 8 were trained in Indian classical form of dance (dancers) and other 8 participants who were not trained in any dance form (non dancers). cVEMP and oVEMP responses were recorded for all the subjects. Non Parametric Mann-Whitney U test revealed no significant difference between dancers and non dancers for the latency and amplitude parameter for cVEMP and oVEMP, i.e. P13, N23 latency and P13-N23 complex amplitude and N10, P14 latency, N10-P14 complex amplitude respectively. The vestibular system comprises of several structures. It is possible that the dance style practiced by the dancer's group assessed in this study does not contribute towards improving the plasticity of the sacculocollic and otolith-ocular pathways. It can be concluded that not all forms of dance training brings about a change in the plasticity of the sacculocollic and otolithocular pathways. PMID- 26557345 TI - Pediatric Physicians' Referral of Children Aged 0-3 Years for Audiological Evaluation in the Public Health Care Sector. AB - The current study aimed to determine the current practice of pediatric physicians in the referral of children (0-3 years) for further audiological evaluation in the South African public health care sector. Sixty three pediatric physicians comprising of pediatricians, neonatologists, medical officers, registrars and interns from three academic hospitals completed a self- administered questionnaire. Most participants reported referrals to an audiologist when hearing loss was suspected. An average of eight risk factors for hearing loss listed on the Health Professionals Council of South Africa (HPCSA) 2007 position statement were identified by participants, indicating the need for referral. Generally, participants reported that referral/s occurred easily within the respective hospitals. Results highlight that pediatric physicians are aware of the role that audiologists play in the diagnosis and management of hearing loss, are involved in the referral of children that are at risk for hearing loss, and have awareness of some of the known risk factors associated with hearing loss. Further education regarding other risk factors is required in order to increase referral/s, and ensure appropriate referral of children at risk for hearing loss. PMID- 26557346 TI - Pediatric Evaluation of the ClearVoiceTM Speech Enhancement Algorithm in Everyday Life. AB - ClearVoiceTM enables Advanced Bionics cochlear implant users to improve their speech understanding in difficult listening environments, without compromising performance in quiet situations. The aim of the study was to evaluate the benefits of ClearVoice in children. Children between six and fourteen years of age randomly tested two modalities of ClearVoice for one month each. The baseline program, HiRes 120TM, and both ClearVoice programs were evaluated with a sentence test in quiet and noise. Parents and teachers completed a questionnaire related to everyday noisy situations. The switchover to ClearVoice was uneventful for both modalities. Adjustments to thresholds and comfort levels were required. Seven out of the nine children preferred a ClearVoice program. No impact of ClearVoice on performance in quiet was observed and both modalities of ClearVoice improved speech understanding in noise compared to the baseline program, significantly with ClearVoice high. Positive outcomes were obtained from the questionnaires and discussions with parents and children. This study showed that children benefited from using ClearVoice in their daily life. There was a clear trend towards improved speech understanding in noise with ClearVoice, without affecting performance in quiet; therefore ClearVoice can be used by children all day, without having to change programs. PMID- 26557347 TI - Effect of Stimulus Polarity on Speech Evoked Auditory Brainstem Response. AB - The aim of the present study was to investigate the effect of stimulus polarity on speech evoked auditory brainstem response (ABR). In order to accomplish it, speech evoked ABR was recorded with various stimulus polarities from 17 normally hearing adults. The result of the study shows differential effect of stimulus polarity on components of speech evoked ABR. Latency of peaks for onset, sustained and offset responses of speech evoked ABR were found to be not significantly different across stimulus polarities. In contrast, the amplitude of first formant and high frequency components was found to be significantly reduced for alternating polarity compared to single polarity, while amplitude of fundamental frequency response was not affected by polarity of the stimuli. Thus speech evoked ABR may be recorded using single polarity rather than using alternating polarities. PMID- 26557348 TI - Language Outcomes Using Hearing Aids in Children with Auditory Dys-Synchrony. AB - There is a considerable debate on the use of hearing aid in children with auditory dys-synchrony (AD). To current date there are no similar Studies which show the effect of acoustic amplification on outcomes on speech and language development in children with AD are found in the literature. Thus, in the present study three children diagnosed to have AD were recruited and subjected to hearing aid trial and fitting based on the late latency response thresholds. Ranging from 7 months to 41 months of intervention period, each child's language age was reassessed and compared with that of their pre-therapy language age. The comparison showed a good improvement in receptive age, though the children had moderate to severe degree of hearing loss. But their expressive age was significantly delayed irrespective of their age of identification and duration of intervention. Thus the delay in expression with a good amount of improvement in reception can be a characteristic of an AD child with amplification. PMID- 26557349 TI - Optimizing Stimulus Repetition Rate for Recording Ocular Vestibular Evoked Myogenic Potential Elicited by Air-Conduction Tone Bursts of 500 Hz. AB - Amidst several publications reporting the effects of stimulus-related parameters on ocular vestibular evoked myogenic potential (oVEMP), the effect of the repetition rate on oVEMP responses has largely gone unexplored. Studies have used a repetition rate of ~5.1 Hz mainly due to a presumption that oVEMP, like cervical VEMP, should produce best responses for ~5 Hz, although there is paucity of experimental evidence to support this hypothesis. 52 healthy individuals in the age range of 17-35 years underwent air-conduction oVEMP elicited by 500 Hz tone-bursts using seven different repetition rates (3.1, 5.1, 10.1, 15.1, 20.1, 25.1 and 30.1 Hz). The results revealed a tendency for prolongation of latencies and reduction in amplitude with increasing repetition rate. However, significantly longer latencies were observed only for 20.1 Hz and larger amplitudes for 3.1 and 5.1 Hz (P<0.05). There was no significant difference between the rates of 3.1 Hz and 5.1 Hz. However 3.1 Hz produced poorer signal-to noise ratio and required considerably longer time and thereby had lesser efficiency than 5.1 Hz (P<0.05). This would also result in higher fatigue and irritation levels considering the physical act of maintaining a supero-medial gaze. Thus the use of 5.1 Hz is recommended for clinical recording of oVEMP. PMID- 26557350 TI - Influence of Native and Non-Native Multitalker Babble on Speech Recognition in Noise. AB - The aim of the study was to assess speech recognition in noise using multitalker babble of native and non-native language at two different signal to noise ratios. The speech recognition in noise was assessed on 60 participants (18 to 30 years) with normal hearing sensitivity, having Malayalam and Kannada as their native language. For this purpose, 6 and 10 multitalker babble were generated in Kannada and Malayalam language. Speech recognition was assessed for native listeners of both the languages in the presence of native and non-native multitalker babble. Results showed that the speech recognition in noise was significantly higher for 0 dB signal to noise ratio (SNR) compared to -3 dB SNR for both the languages. Performance of Kannada Listeners was significantly higher in the presence of native (Kannada) babble compared to non-native babble (Malayalam). However, this was not same with the Malayalam listeners wherein they performed equally well with native (Malayalam) as well as non-native babble (Kannada). The results of the present study highlight the importance of using native multitalker babble for Kannada listeners in lieu of non-native babble and, considering the importance of each SNR for estimating speech recognition in noise scores. Further research is needed to assess speech recognition in Malayalam listeners in the presence of other non-native backgrounds of various types. PMID- 26557351 TI - Evaluation of Temporal Difference Limen in Preoperative Non-Invasive Ear Canal Audiometry as a Predictive Factor for Speech Perception after Cochlear Implantation. AB - The temporal difference limen (TDL) can be measured with noninvasive electrical ear canal stimulation. The objective of the study wa to determine the role of preoperative TDL measurements in predicting patients' speech perception after cochlear implantation. We carried out a retrospective chart analysis of fifty four cochlear implant (CI) patients with preoperative TDL and postoperative bisyllabic word recognition measurements in Helsinki University Central Hospital between March 1994 and March 2011. Our results show that there is no correlation between TDL and postoperative speech perception. However, patient's advancing age correlates with longer TDL but not-directly with poorer speech perception. The results are in line with previous results concerning the lack of predictive value of preoperativ TDL measurements in CI patients. PMID- 26557352 TI - The Relationship Between Acceptable Noise Level and Electrophysiologic Auditory Brainstem and Cortical Signal to Noise Ratios. AB - The following objectives of the study were formulated: i) to investigate differences in measured signal to noise ratios while recording speech-evoked auditory brainstem response (cABR) and cortical late latency response (LLR) in low and high acceptable noise level (ANL) groups; and ii) to compare peak to peak amplitude of cABR (V-A) and LLR (N1-P2) in low and high ANL groups. A total of 23 normal hearing participants was included in the study. One shot replicative and partly exploratory research design was utilized to study the effect of signal to noise ratio in a recorded waveform on afferent mechanism, assessed by cABR and LLR on participants having values of ANL of <=7 (low ANL group) and >=13 (high ANL group). There were no differences in signal to noise ratio in the recorded waveforms of cABR and LLR between low and high ANL groups at both brainstem and cortical levels. However, the peak to peak amplitude of V-A of cABR and N1-P2 of LLR were both statistically larger in the high ANL group compared to their counterpart. The signal to noise ratio in recorded waveforms did not differentiated cABR (V-A) or LLR (N1-P2) in low and high ANL groups. However, Larger peak to peak amplitudes in the high ANL group suggests differences higher processing centers in the upper brainstem to the auditory cortex. The findings of the study may be useful in determining the patient acceptability of noise. PMID- 26557353 TI - Survey on Infant Hearing Loss at Caritas Baby Hospital in Bethlehem-Palestine. AB - This study describes the epidemiology of infants' hearing loss (IHL) among patients under 3 months of age at Caritas Baby Hospital, the only pediatric hospital in Palestine. It was aimed to demonstrate that IHL is a major health problem in Palestine and to assess the first available data of the newborn hearing screening program conducted between September 25, 2006 and December 31, 2011. Data was uploaded and analyzed using Microsoft Excel and the Statistical Package for the Social Sciences software (SPSS version 21). A total of 8144 infants were tested, 4812 (59%) were males and 3332 (41%) were females. As to their origin, 72% (5886) came from the Bethlehem district, 25% (2044) from the Hebron district, while 3% (214) from the other Palestinian districts (Jericho, Ramallah, Nablus, Jenin and Jerusalem). The transient evoked otoacoustic emissions (TEOAEs) and the automated auditory brainstem response were used according to the manufacturer guidelines. The results were interpreted according to the indications of the American Academy of Pediatrics, the National Institutes of Health, and the European Consensus Development Conference on Neonatal Hearing Screening. Out of the 8144 infants tested, 1507 (14.6%) did not pass the 1(st) test, 477 (32.8%) of these 1507 infants failed retesting, while 498 (33%) patients were lost to follow-up. Only 152 (31.9%) patients that failed retesting went to an audiologist. The audiologist evaluation revealed that 101 (66.4%) patients presented with a mild-moderate or profound hearing loss according to the Bureau International of Audiophonologie standards, 44 (28.9%) patients had otitis media, whereas 7 cases (4.7%) had no hearing disorders. The overall unadjusted percentage of hearing loss was 1.24%, and the adjusted overall percentage was 1.85%. The chart review showed that jaundice, sepsis, prematurity, lung disease were more common among the affected patients. The high prevalence of childhood deafness in Palestine is of utmost importance and deserves immediate attention on the part of the Palestinian government. Meanwhile, Caritas Baby Hospital undertook to set up a newborn hearing screening unit utilizing the TEOAE method. PMID- 26557354 TI - Short-Term Musical Training and Pyschoacoustical Abilities. AB - The aim of the study was to assess the effect of short-term perceptual training of music on some psycho-acoustical measures. The study was carried out in three phases. In first the phase pre-training evaluation was done which included raga identification and various psycho acoustical tests. Psycho-acoustical tests included measurement of differential limen of frequency and intensity, duration discrimination, gap detection, modulation detection, backward masking and duration pattern test. In the second phase, auditory perceptual training was given for raga identification and in the third phase post- training evaluation was done though same tests as mentioned in pre-training phase. A total of 10 normal hearing adults (7 males, 3 females) in the age range of 18-25 years participated in the study. The results revealed that all the subjects performed significantly better on raga identification after training. However; there was no significant difference in psycho-acoustical measures in pre and post-training. PMID- 26557355 TI - Effect of Repetition Rate on Speech Evoked Auditory Brainstem Response in Younger and Middle Aged Individuals. AB - Speech evoked auditory brainstem responses depicts the neural encoding of speech at the level of brainstem. This study was designed to evaluate the neural encoding of speech at the brainstem in younger population and middle-aged population at three different repetition rates (6.9, 10.9 and 15.4). Speech evoked auditory brainstem response was recorded from 84 participants (young participants=42, middle aged participants=42) with normal hearing sensitivity. The latency of wave V and amplitude of the fundamental frequency, first formant frequency and second formant frequency was calculated. Results showed that the latency of wave V was prolonged for middle-aged individuals for all three repetition rates compared to the younger participants. The results of the present study also revealed that there was no difference in encoding of fundamental frequency between middle aged and younger individuals at any of the repetition rates. However, increase in repetition rate did affect the encoding of the fundamental frequency in middle-aged individuals. The above results suggest a differential effect of repetition rate on wave V latency and encoding of fundamental frequency. Further, it was noticed that repetition rate did not affect the amplitude of first formant frequency or second formant frequency in middle aged participants compared to the younger participants. PMID- 26557356 TI - Psychoacoustic Characteristics of Tinnitus in Individuals with Auditory Neuropathy Spectrum Disorder. AB - The study aimed at understanding the psychoacoustic characteristics of tinnitus in individuals with auditory neuropathy spectrum disorder (ANSD). It attempts to assess the pitch and intensity of loudness of tinnitus matched by individuals with ANSD. Fifty individuals who were diagnosed as having auditory neuropathy spectrum disorder were included in the study. Tinnitus evaluation was carried out where the individuals matched the frequency and intensity of loudness of the tinnitus. The results of the study shows that pitch matched by majority of patients with ANSD is predominantly low pitched (<1000 Hz). The frequency of tinnitus matched by the patients with ANSD also correlated with the degree of maximal hearing loss. The intensity of loudness of the tinnitus was around 10-15 dB higher than their threshold in majority of the patients considered in the study. There was a weak negative correlation for the matched frequency and intensity of loudness. The results of the study suggest that majority of individuals with low frequency hearing loss had low pitched tinnitus. Thus, there could be discordant damage between outer and inner hair cells, abnormal firing of auditory nerve in individuals with ANSD which can lead to tinnitus. Thus, it can help to understand the physiology of tinnitus in individuals with ANSD. PMID- 26557357 TI - Effect of Compression, Digital Noise Reduction and Directionality on Envelope Difference Index, Log-Likelihood Ratio and Perceived Quality. AB - The aim of the present study was to evaluate the use of the envelope difference index (EDI) and log-likelihood ratio (LLR) to quantify the independent and interactive effects of wide dynamic range compression, digital noise reduction and directionality, and to carry out self-rated quality measures. A recorded sentence embedded in speech spectrum noise at +5 dB signal to noise ratio was presented to a four channel digital hearing aid and the output was recorded with different combinations of algorithms at 30, 45 and 70 dB HL levels of presentation through a 2 cc coupler. EDI and LLR were obtained in comparison with the original signal using MATLAB software. In addition, thirty participants with normal hearing sensitivity rated the output on the loudness and clarity parameters of quality. The results revealed that the temporal changes happening at the output is independent of the number of algorithms activated together in a hearing aid. However, at a higher level of presentation, temporal cues are better preserved if all of these algorithms are deactivated. The spectral components speech tend to get affected by the presentation level. The results also indicate the importance of quality rating as this helps in considering whether the spectral and/or temporal deviations created in the hearing aid are desirable or not. PMID- 26557358 TI - Simultaneous Extratympanic Electrocochleography and Auditory Brainstem Responses Revisited. AB - The purpose of this study was to revisit the two-channel, simultaneous click evoked extratympanic electrocochleography and auditory brainstem response (ECoG/ABR) recording technique for clinical use in normal hearing participants. Recording the compound action potential (AP) of the ECoG simultaneously with ABR may be useful when Wave I of the ABR is small or diminished in patients with sensorineural or retrocochlear disorder and minimizes overall test time. In contrast to some previous studies that used the extratympanic electrode both as non-inverting electrode for the ECoG and inverting electrode for ABR, this study maintained separate recording channel montages unique to conventional click evoked ECoG and ABR recordings. That is, the ABR was recorded using a vertical channel (Cz to ipsilateral earlobe), while the ECoG with custom extratympanic electrode was recorded using a horizontal channel (tympanic membrane to contralateral earlobe). The extratympanic electrode is easy to fabricate in house, or can be purchased commercially. Maintaining the conventional ABR montage permits continued use of traditional normative data. Broadband clicks at a fixed level of 85 dB nHL were presented with alternating polarity at stimulus rates of 9.3, 11.3, and 15.3/s. Different stimulation rates were explored to identify the most efficient rate without sacrificing time or waveform morphology. Results revealed larger ECoG AP than ABR Wave I, as expected, and no significant difference across stimulation rate and no interaction effect. Extratympanic electrode placement takes little additional clinic time and may improve the neurodiagnostic utility of the ABR. PMID- 26557359 TI - The Effect of Short-Term Musical Training on Speech Perception in Noise. AB - The aim of the study was to assess the effect of short-term musical training on speech perception in noise. In the present study speech perception in noise was measured pre- and post- short-term musical training. The musical training involved auditory perceptual training for raga identification of two Carnatic ragas. The training was given for eight sessions. A total of 18 normal hearing adults in the age range of 18-25 years participated in the study wherein group 1 consisted of ten individuals who underwent musical training and group 2 consisted of eight individuals who did not undergo any training. Results revealed that post training, speech perception in noise improved significantly in group 1, whereas group 2 did not show any changes in speech perception scores. Thus, short-term musical training shows an enhancement of speech perception in the presence of noise. However, generalization and long-term maintenance of these benefits needs to be evaluated. PMID- 26557360 TI - Habituation of Auditory Steady State Responses Evoked by Amplitude-Modulated Acoustic Signals in Rats. AB - Generation of the auditory steady state responses (ASSR) is commonly explained by the linear combination of random background noise activity and the stationary response. Based on this model, the decrease of amplitude that occurs over the sequential averaging of epochs of the raw data has been exclusively linked to the cancelation of noise. Nevertheless, this behavior might also reflect the non stationary response of the ASSR generators. We tested this hypothesis by characterizing the ASSR time course in rats with different auditory maturational stages. ASSR were evoked by 8-kHz tones of different supra-threshold intensities, modulated in amplitude at 115 Hz. Results show that the ASSR amplitude habituated to the sustained stimulation and that dishabituation occurred when deviant stimuli were presented. ASSR habituation increased as animals became adults, suggesting that the ability to filter acoustic stimuli with no-relevant temporal information increased with age. Results are discussed in terms of the current model of the ASSR generation and analysis procedures. They might have implications for audiometric tests designed to assess hearing in subjects who cannot provide reliable results in the psychophysical trials. PMID- 26557362 TI - Nystagmus in Enlarged Vestibular Aqueduct: A Case Series. AB - Enlarged vestibular aqueduct (EVA) is one of the commonly identified congenital temporal bone abnormalities associated with sensorineural hearing loss. Hearing loss may be unilateral or bilateral, and typically presents at birth or in early childhood. Vestibular symptoms have been reported in up to 50% of affected individuals, and may be delayed in onset until adulthood. The details of nystagmus in patients with EVA have not been previously reported. The objectives were to describe the clinical history, vestibular test findings and nystagmus seen in a case series of patients with enlarged vestibular aqueduct anomaly. Chart review, included computed tomography temporal bones, infrared nystagmography with positional and positioning testing, caloric testing, rotary chair and vibration testing. Clinical history and nystagmus varied among the five patients in this series. All patients were initially presumed to have benign paroxysmal positional vertigo, but repositioning treatments were not effective, prompting referral, further testing and evaluation. In three patients with longstanding vestibular complaints, positional nystagmus was consistently present. One patient had distinct recurrent severe episodes of positional nystagmus. Nystagmus was unidirectional and horizontal. In one case horizontal nystagmus was consistently reproducible with seated head turn to the affected side, and reached 48 d/s. Nystagmus associated with enlarged vestibular aqueduct is often positional, and can be confused with benign paroxysmal positional vertigo. Unexplained vestibular symptoms in patients with unilateral or bilateral sensorineural hearing loss should prompt diagnostic consideration of EVA. PMID- 26557361 TI - Outlook for Tissue Engineering of the Tympanic Membrane. AB - Tympanic membrane perforation is a common problem leading to hearing loss. Despite the autoregenerative activity of the eardrum, chronic perforations require surgery using different materials, from autologous tissue - fascia, cartilage, fat or perichondrium - to paper patch. However, both, surgical procedures (myringoplasty or tympanoplasty) and the materials employed, have a number of limitations. Therefore, the advances in this field are incorporating the principles of tissue engineering, which includes the use of scaffolds, biomolecules and cells. This discipline allows the development of new biocompatible materials that reproduce the structure and mechanical properties of the native tympanic membrane, while it seeks to implement new therapeutic approaches that can be performed in an outpatient setting. Moreover, the creation of an artificial tympanic membrane commercially available would reduce the duration of the surgery and costs. The present review analyzes the current treatment of tympanic perforations and examines the techniques of tissue engineering, either to develop bioartificial constructs, or for tympanic regeneration by using different scaffold materials, bioactive molecules and cells. Finally, it considers the aspects regarding the design of scaffolds, release of biomolecules and use of cells that must be taken into account in the tissue engineering of the eardrum. The possibility of developing new biomaterials, as well as constructs commercially available, makes tissue engineering a discipline with great potential, capable of overcoming the drawbacks of current surgical procedures. PMID- 26557363 TI - Effect of Compression Ratio on Perception of Time Compressed Phonemically Balanced Words in Kannada and Monosyllables. AB - The present study attempted to study perception of time-compressed speech and the effect of compression ratio for phonemically balanced (PB) word lists in Kannada and monosyllables. The test was administered on 30 normal hearing individuals at compression ratios of 40%, 50%, 60%, 70% and 80% for PB words in Kannada and monosyllables. The results of the study showed that the speech identification scores for time-compressed speech reduced with increase in compression ratio. The scores were better for monosyllables compared to PB words especially at higher compression ratios. The study provides speech identification scores at different compression ratio for PB words and monosyllables in individuals with normal hearing. The results of the study also showed that the scores did not vary across gender for all the compression ratios for both the stimuli. The same test material needs to be compared the clinical population with central auditory processing disorder for clinical validation of the present results. PMID- 26557364 TI - Apogeotropic Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo: Some Clinical and Therapeutic Considerations. AB - We lately reported the cases of patients complaining positional vertigo whose nystagmic pattern was that of a peripheral torsional vertical positional down beating nystagmus originating from a lithiasis of the non-ampullary arm of the posterior semicircular canal (PSC). We considered this particular pathological picture the apogeotropic variant of PSC benign paroxysmal positional vertigo (BPPV). Since the description of the pilot cases we observed more than 150 patients showing the same clinical sign and course of symptoms. In this paper we describe, in detail, both nystagmus of apogeotropic PSC BPPV (A-PSC BPPV) and symptoms reported by patients trying to give a reasonable explanation for these clinical features. Moreover we developed two specific physical therapies directed to cure A-PSC BPPV. Preliminary results of these techniques are related. PMID- 26557365 TI - Factors associated with excessive polypharmacy in older people. AB - BACKGROUND: Older people are a growing population. They live longer, but often have multiple chronic diseases. As a consequence, they are taking many different kind of medicines, while their vulnerability to pharmaceutical products is increased. The objective of this study is to describe the medicine utilization pattern in people aged 65 years and older in Belgium, and to estimate the prevalence and the determinants of excessive polypharmacy. METHODS: Data were used from the Belgian Health Interview Survey carried out in 2008. Each respondent was asked to show to the interviewer all medicines that he/she had taken in the 24 h prior to the interview. Excessive polypharmacy was defined as the use of nine different kind of medicines or more in the past 24 h; the relation with the Region of residence, age, gender and additional factors, such as socioeconomic status, living situation, health status and contacts with health services, was explored through multivariate models. RESULTS: Eight percent of the older people (65 years or more) belong to the excessive polypharmacy group. Factors most strongly associated with excessive polypharmacy are: having a longstanding illness, chronic condition or handicap, at least 1 contact with a general practitioner in past 2 months and self-reported depression during the last year. Ninety percent of persons in the excessive polypharmacy group are taking medicines active on the cardiovascular system. CONCLUSIONS: In order to optimize the use of medicines, it is necessary to find a balance between adequate treatment of diseases and avoiding adverse effects of medicines. Interventions should aim to increase awareness among healthcare professionals and patients; they should focus on general practitioners and patients with cardiovascular diseases, those suffering from depression and those aged 80 years and over. Monitoring excessive polypharmacy in the older population remains important. Further studies should explore more in depth other and more specific determinants of excessive polypharmacy. PMID- 26557366 TI - Use of plasma metanephrine to aid adrenal venous sampling in combined aldosterone and cortisol over-secretion. AB - In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was measured during AVS to successfully circumvent this problem. A 55-year-old hypertensive male had raised plasma aldosterone/renin ratios and PA confirmed by fludrocortisone suppression testing. Failure of plasma cortisol to suppress overnight following dexamethasone and persistently suppressed corticotrophin were consistent with adrenal hypercortisolism. On AVS, comparison of adrenal and peripheral A/F ratios (left 5.7 vs peripheral 1.0; right 1.7 vs peripheral 1.1) suggested bilateral aldosterone production, with the left gland dominant but without contralateral suppression. However, using aldosterone/metanephrine ratios (left 9.7 vs peripheral 2.4; right 1.3 vs peripheral 2.5), aldosterone production lateralized to the left with good contralateral suppression. The patient underwent left laparoscopic adrenalectomy with peri-operative glucocorticoid supplementation to prevent adrenal insufficiency. Pathological examination revealed adrenal cortical adenomas producing both cortisol and aldosterone within a background of aldosterone producing cell clusters. Hypertension improved and cured of PA and hypercortisolism were confirmed by negative post-operative fludrocortisone suppression and overnight 1 mg dexamethasone suppression testing. Routine dexamethasone suppression testing in patients with PA permits detection of concurrent hypercortisolism which can confound AVS results and cause unilateral PA to be misdiagnosed as bilateral with patients thereby denied potentially curative surgical treatment. In such patients, measurement of plasma metanephrine during AVS may overcome this issue. LEARNING POINTS: Simultaneous autonomous overproduction of cortisol and aldosterone is increasingly recognised although still apparently uncommon.Because cortisol levels are used during AVS to correct for differences in dilution of adrenal with non-adrenal venous blood when assessing for lateralisation, unilateral cortisol overproduction with contralateral suppression could confound the interpretation of AVS resultsMeasuring plasma metanephrine during AVS to calculate lateralisation ratios may circumvent this problem. PMID- 26557367 TI - Evaluation of Ceftriaxone utilization in internal medicine wards of general hospitals in Addis Ababa, Ethiopia: a comparative retrospective study. AB - OBJECTIVES: The irrational use of reserved antimicrobials, such as ceftriaxone, is one of the global public health issues particularly to low income countries like Ethiopia, leading to high costs of treatment or therapeutic failure. The purpose of the present study, thus, is to evaluate the appropriateness of ceftriaxone utilization in the medicine wards of general hospitals in Addis Ababa, with reference to the standard treatment guideline of Ethiopia for general hospitals. METHODS: An institution based retrospective cross sectional study design was conducted in the internal medicine wards of Hayat and Zewditu Memorial hospital from 20 January to 20 February, 2014. Medication records of all patients who were admitted and prescribed with ceftriaxone during the previous one year to the study period were evaluated in reference to the Ethiopian Standard Treatment Guideline (STG 2010) for general hospitals. RESULTS: The proportion of patients who received ceftriaxone was 59.3 % and 49 % in the public & the private hospital, respectively. Pneumonia, meningitis and sepsis were the common diagnoses in which ceftriaxone was prescribed in both hospitals. Maintenance fluids were the top ranked co-prescribed drugs in either hospital. Only 48.9 % in the public hospital and 44.6 % of records in the private hospital showed overall ceftriaxone use compliance to the guideline. Days of hospital stay was associated with appropriateness of ceftriaxone therapy. CONCLUSIONS: Even though ceftriaxone is one of the most commonly prescribed drugs in both hospitals, appropriateness of its use, according to the Ethiopian standard treatment guideline, was less than expected. This was so mainly from its indication and duration of therapy. Increasing the duration of hospital stay, however, showed to improve the appropriateness of ceftriaxone utilization. PMID- 26557368 TI - Engaging Nigerian community pharmacists in public health programs: assessment of their knowledge, attitude and practice in Enugu metropolis. AB - OBJECTIVES: The Nigerian health sector battles with control of infectious diseases and emerging non-communicable diseases. Number of healthcare personnel involved in public health programs need to be boosted to contain the health challenges of the country. Therefore, it is important to assess whether community pharmacists in Nigeria could be engaged in the promotion and delivery of various public health interventions. This study aimed to assess level of knowledge, attitude and practice of public health by community pharmacists. METHODS: The cross sectional survey was carried out in Enugu metropolis. Questionnaire items were developed from expert literature. Percentage satisfactory knowledge and practice were obtained by determining the percentage of community pharmacists that were able to list more than 2 activities or that stated the correct answer. Attitude score represents the average score on the 5 point Likert scale for each item. Chi square and Fisher's exact test were used to test for statistically significant difference in knowledge, attitude and practice of public health between different groups of community pharmacists. RESULTS: Forty pharmacists participated in the survey. About one third of the participants had satisfactory knowledge of public health. With the exception of one item in attitude assessment, average item score ranged from 'agreed' to 'strongly agreed'. Study participants scored below satisfactory on practice of public health. Knowledge, attitude and practice of public health were not influenced by years of practice, qualification and prior public health experience. Reported barriers to the practice of public health include inadequate funds, lack of time, lack of space, cooperation of clients, inadequate staff, government regulation, insufficient knowledge, and remuneration. CONCLUSIONS: Level of knowledge and practice of public health by community pharmacists were not satisfactory although they had a positive attitude towards practice of public health. The findings highlight the importance of educational interventions targeted towards practicing community pharmacists to improve their knowledge level on public health issues. Providing incentives for public health services rendered could increase community pharmacists' engagement in public health activities. PMID- 26557369 TI - CanVasc recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides - Executive summary. AB - The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context. PMID- 26557370 TI - Why does the gout attack stop? A roadmap for the immune pathogenesis of gout. AB - Gout is one of the most severe and frequent rheumatic diseases. Clinical manifestations of gout arise from uric acid crystal deposition in the musculoskeletal tissue. At high concentrations of uric acid in the body (hyperuricaemia), needle-shaped monosodium urate (MSU) crystals are formed. The structures are ingested by neutrophils and monocytes and thereby trigger robust activation of the inflammasome, an intracellular protein complex mounting an inflammatory response. Inflammasome activation builds interleukin-1, which acts as a proinflammatory mediator and induces vasodilation, recruitment of additional leucocytes and the expression of proinflammatory cytokines and chemokines. This process is associated with the clinical manifestation of an acute gout attack. Such attacks, however, stop rather rapidly and the process of resolution of inflammation in gout is now better defined. Neutrophils having ingested MSU crystals undergo a specific form of cell death called NETosis, which is characterised by the formation of neutrophil extracellular traps (NETs). During this process, DNA is extruded, allowing the dense packaging of MSU crystals as well as the degradation of proinflammatory cytokines, thereby allowing the stopping of the inflammatory process. Reactive oxygen species are essential for forming NETs and for allowing the resolution of inflammation in gout. This process of NETosis is critical for understanding tophaceous gout, since tophi are composed of NETs and densely packed MSU crystals. PMID- 26557371 TI - Antirheumatic drugs and reproduction in women and men with chronic arthritis. AB - The impact of rheumatic disease on fertility and reproduction can be remarkable. Many disease-related factors can influence patients' sexual functioning, perturb fertility and limit family planning. Antirheumatic pharmacological treatment can also have a crucial role in this field. Proper counselling, preferably provided by a multidisciplinary team of rheumatologists, obstetricians, gynaecologists and neonatologists, is recommended for patients taking antirheumatic drugs, not only at the beginning, but also during the course of treatment. Paternal exposure to antirheumatic drugs was not found to be specifically associated with congenital malformation and adverse pregnancy outcome, therefore discontinuation of these drugs while planning for conception should be weighed against the risk of disease flare. Drugs in Food and Drug Administration (FDA) category 'X' should be withdrawn in a timely manner in women who desire a pregnancy. Meanwhile, disease control can be achieved with anti-tumour necrosis factor (TNF)-alpha agents, which are not teratogenic drugs. If maternal disease control is permissive, they can be stopped as soon as the pregnancy test turns positive and be resumed during pregnancy in case of a flare. PMID- 26557372 TI - The osteocyte: key player in regulating bone turnover. AB - Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell-cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading. PMID- 26557373 TI - Glucocorticoids: bad or safe for the bones? AB - Until recently, patients with rheumatoid arthritis (RA) were treated with monotherapy using conventional drugs such as sulfasalazine, antimalarials, intramuscular gold and methotrexate, which often leads to persistent arthritis, loss of functional capacity and decreased quality of life. The use of high-dose glucocorticoids (GCs) and active RA are both associated with generalised bone loss and fractures, while GCs have a strong immunosuppressive effect. With the introduction of very effective tumour-necrosis factor-blockers and other biologics, clinical remission is a realistic target in around half of the early patients with RA; the same appears true for the use of methotrexate with chronic low dose or initially high-dose GCs. With the use of a treat-to-target strategy focusing on clinical remission or low disease activity in early patients with RA, the negative effects of systemic inflammation on bone can be inhibited and local bone loss (in the joints), and generalised bone loss at the spine and hips, can be limited or prevented. Whether this also leads to a reduction in vertebral and non-vertebral fractures remains to be demonstrated. Another issue is, in other systemic rheumatic diseases in which treatment options are smaller and less effective than in RA, local and systemic bone loss may still occur. PMID- 26557374 TI - New insights into treatment of osteoporosis in postmenopausal women. AB - For the prevention of fractures, antiresorptive drugs (bisphosphonates and denosumab) that decrease high bone resorption and, secondarily, also bone formation, are the mainstream of therapy. Osteoanabolic drugs, such as teriparatide, increase bone formation more than bone resorption, and are used in severe osteoporosis, including patients treated with antiresorptive drugs who still lose bone and have recurrent fractures. New potential drugs for fracture prevention that uncouple bone resorption from bone formation include odanacatib, a specific inhibitor of cathepsin-K, the enzyme that degrades bone collagen type I, that inhibits bone resorption and only temporarily bone formation, and monoclonal antibodies against sclerostin (romosozumab, blosozumab), that stimulate bone formation and decrease bone resorption. PMID- 26557375 TI - Non-radiographic axial spondyloarthritis and ankylosing spondylitis: what are the similarities and differences? AB - The development of the axial spondyloarthritis and ankylosing spondylitis (ASAS) classification criteria has had several implications for our understanding of the entire spectrum of spondyloarthritides (SpA). Going beyond the modified New York criteria, which concentrate on conventional radiographs of the sacroiliac joints (SIJ) for the classification of ankylosing spondylitis, the ASAS criteria add active inflammation of the SIJ as obtained by MRI and human leucocyte antigen (HLA) B27 to classify patients with chronic back pain starting at a young age as axial SpA (axSpA). AxSpA should be considered as one disease that includes AS, the radiographic form, as well as the non-radiographic (nr-axSpA) form. Similarities and differences between these subgroups have been described in 3 studies: 1 local study, 1 national study (German SpA Inception Cohort) and 1 international study mainly conducted to test the efficacy of a tumour necrosis factor alpha blocker. Most clinical features and assessments of axSpA showed the same prevalence in patients with and without radiographic changes. However, some differences have been observed: the male:female ratio, the proportion of patients with objective signs of inflammation such as bone marrow oedema as detected by MRI, and the proportion of patients with increased levels of C reactive protein were higher in patients with AS. Importantly, these factors have also been identified as prognostic factors for more severe disease in terms of new bone formation. Thus, nr-axSpA may represent an early stage of AS but may also just be an abortive form of a disease which does cause much pain but which may also never lead to structural changes of the axial skeleton. Since the cut-off between nr axSpA and AS is artificial and unreliable, we think that the term nr-axSpA should not be used for diagnosis but only for classification for historical reasons. PMID- 26557376 TI - Old and new treatment targets in axial spondyloarthritis. AB - Two main treatment targets in axial spondyloarthritis (axSpA) could be currently defined: (1) reduction of inflammation resulting in control of signs and symptoms such as pain and stiffness and (2) prevention or retardation of structural damage progression in the spine resulting in preservation of functional status and improvement in the long-term outcome. A good control of signs and symptoms could be successfully achieved nowadays in the majority of patients treated with non steroidal anti-inflammatory drugs (NSAIDs-the first-line therapy in axSpA) and with tumour necrosis factor (TNF) alpha blockers (the second-line therapy, if NSAIDs fail). Several pipeline drugs including interleukin (IL) 17 and IL-23 antagonists might be helpful in the immediate future in achievement of this treatment target in case of inefficacy of NSAIDs and TNFalpha blockers. Retardation of radiographical spinal progression in axSpA-disease modification-is currently a much more challenging task than a good symptom control. In this review, we discuss symptomatic and possible disease-modifying properties of current and forthcoming treatment options for axSpA. PMID- 26557377 TI - Treatment of complex regional pain syndrome type I with bisphosphonates. AB - Complex regional pain syndrome type I (CRPS-I) is a common and disabling disorder affecting a peripheral limb, usually developing after a trauma to an extremity. CRPS-I is characterised by presence of spontaneous pain, allodynia and hyperalgesia, disproportionate to the inciting event and by a variety of autonomic disturbances and trophic abnormalities. The pathophysiology of CRPS-I has not been fully understood. Experimental models have suggested that an initial triggering event may produce the release of proinflammatory neuropeptides and cytokines, generating a sort of neurogenic inflammation. Thereafter, increased microvascular permeability and intramedullary pressure, reduced oxygen extraction and cellular hypoxia maintain and make the disease worse, producing metabolic tissue acidosis. In this context, it is probable that, far from being a key player, the sympathetic nervous system contributes interacting with these mechanisms and producing vasomotor disturbances. Bisphosphonates (BPs) are potent inhibitors of osteoclastic activity widely used for the management of osteoporosis and other metabolic bone diseases. Their primary pharmacological action is the reduction of bone turnover. An enhanced osteoclastic activity has never been clearly demonstrated in CRPS-I. Therefore, it is likely that the positive effects of BPs in this condition are not related to their antiresorptive properties, but to a more complex interaction between these pharmacological agents and the pathophysiological mechanisms underlying CRPS-I. Results of several clinical trials have suggested the potential beneficial effects of BPs in CRPS-I. In five randomised controlled trials, oral and intravenous alendronate and intravenous clodronate, pamidronate and neridronate demonstrated to be effective in reducing pain and improving physical function in patients presenting with CRPS-I, with a good profile of safety and tolerability. Although these trials have a number of limitations, including the small samples enrolled, there is sufficient evidence to support the use of BPs as agents of choice in the management of CRPS-I. PMID- 26557378 TI - Rheumatoid arthritis treatment: the earlier the better to prevent joint damage. AB - The management of rheumatoid arthritis has undergone major advances in recent years, both in terms of the drugs armamentarium and therapeutic strategy. Treating disease to target, aiming at remission, through a tight control protocol is regarded as the standard of care. Reaching clinical and radiographic disease remission has therefore become an achievable goal. Increasing evidence has demonstrated that early diagnosis, prompt treatment initiation and early achievement of remission are the major predictors of long-term clinical, functional and radiographic outcomes. Concentrating efforts in controlling disease activity in a very early window of opportunity offers unique sustained benefits. In this short review, we analysed the available evidence supporting the value of treating rheumatoid arthritis early and the impact on disease outcomes, with particular focus on radiographic progression. PMID- 26557379 TI - Pathophysiology of osteoarthritis: canonical NF-kappaB/IKKbeta-dependent and kinase-independent effects of IKKalpha in cartilage degradation and chondrocyte differentiation. AB - Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor kappaB (NF-kappaB) family orchestrate mechanical, inflammatory and oxidative stress-activated processes, thus representing a potential therapeutic target in OA disease. The two pivotal kinases, IkappaB kinase (IKK) alpha and IKKbeta, activate NF-kappaB dimers that might translocate to the nucleus and regulate the expression of specific target genes involved in extracellular matrix remodelling and terminal differentiation of chondrocytes. IKKalpha, required for the activation of the so-called non canonical pathway, has a number of NF-kappaB-independent and kinase-independent functions in vivo and in vitro, including controlling chondrocyte hypertrophic differentiation and collagenase activity. In this short review, we will discuss the role of NF-kappaB signalling in OA pathology, with emphasis on the functional effects of IKKalpha that are independent of its kinase activity and NF-kappaB activation. PMID- 26557380 TI - Early knee osteoarthritis. AB - Concepts regarding osteoarthritis, the most common joint disease, have dramatically changed in the past decade thanks to the development of new imaging techniques and the widespread use of arthroscopy that permits direct visualisation of intra-articular tissues and structure. MRI and ultrasound allow the early detection of pre-radiographic structural changes not only in the peri articular bone but also in the cartilage, menisci, synovial membrane, ligaments and fat pad. The significance of MRI findings such as cartilage defects, bone marrow lesions, synovial inflammation/effusions and meniscal tears in patients without radiographic signs of osteoarthritis is not fully understood. Nevertheless, early joint tissue changes are associated with symptoms and, in some cases, with progression of disease. In this short review, we discuss the emerging concept of early osteoarthritis localised to the knee based on recently updated knowledge. We highlight the need for a new definition of early osteoarthritis that will permit the identification of patients at high risk of osteoarthritis progression and to initiate early treatment interventions. PMID- 26557381 TI - Structural integrity versus radiographic progression in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic, progressive and inflammatory disease often leading to irreversible destruction of articular structures and consequent disability. The key steps of RA pathogenetic mechanisms are the break of immune tolerance and the production of autoantibodies, followed by systemic and local inflammation resulting in damage of both subchondral bone (erosion) and cartilage (joint space narrowing (JSN)). Evidences from clinical trials suggest that erosions and JSN are the result of inter-related but partly independent pathogenetic pathways, in both cases mediated by pro-inflammatory cytokines, even if a direct effect of cyclic citrullinated peptides (anticitrullinated protein antibodies, ACPAs) on bone damage had been postulated. As a consequence, the suppression of inflammation provided by synthetic and biological disease modifying antirheumatic drugs results in a decreased progression of bone and cartilage damage, supporting the effectiveness of the treat-to-target strategy. Nevertheless, radiographic progression may also be detected in patients achieving a sustained clinical remission. Two main reasons for this apparent uncoupling between clinical synovitis and damage progression should be considered. First, in some cases, the use of composite indices to define remission may not be completely adequate to identify residual disease activity, requiring the concomitant introduction of more sensible tools such as imaging. Second, the direct effect of biological drugs on bone destruction inducers, such as pro inflammatory cytokines, may explain the suppression of radiographic progression despite the persistence of clinical synovitis. In this review, we discuss the link between autoimmunity, inflammation, joint damage and disability, focusing on how radiographic progression may predict functional disability. PMID- 26557382 TI - Bone and TNF in rheumatoid arthritis: clinical implications. AB - Experimental data have demonstrated that tumour necrosis factor (TNF) plays a significant role in systemic and local bone loss related to rheumatoid arthritis (RA). In clinical studies on patients with RA, treatment with TNF inhibitors was able to arrest systemic bone loss assessed by bone mineral density and bone turnover markers, but there is scarce evidence of a clinically meaningful effect of TNF inhibition in preventing fractures. TNF inhibitors showed a higher efficacy in reducing radiographic progression related to the disease compared to methotrexate in randomised clinical trials. Data from observational studies seem to confirm the effectiveness of anti-TNF therapy in reducing joint damage evolution. PMID- 26557383 TI - Systemic lupus erythematosus and fractures. AB - Since survival of patients with systemic lupus erythematosus (SLE) has improved over the past decades, increasing attention is focused on complications of the disease. Osteoporosis and fractures contribute to damage in the second most frequently involved organ system in SLE: the musculoskeletal system. Recent studies have reported a high frequency of reduced bone mineral density in SLE, and an increased risk of peripheral and vertebral fractures. The incidence of symptomatic fractures is increased 1.2-4.7-fold in patients with SLE. A large population-based study on 4343 patients with SLE and 21 780 age-matched and sex matched controls, demonstrated previous glucocorticoid use and longer disease duration as important risk factors for symptomatic fractures in SLE. Prevalent vertebral fractures are demonstrated in 18-50% of these relatively young patients, and one in three of these patients has normal bone density. The aetiology of bone loss in SLE is supposed to be multifactorial, involving clinical osteoporosis risk factors, systemic inflammation, serological factors, metabolic factors, hormonal factors, medication-induced adverse effects and, possibly, genetic factors. A 6-year follow-up study on Dutch patients with SLE revealed that low 25-hydroxyvitamin D serum levels, low body mass index and baseline use of antimalarials were associated with bone loss. In addition, a dose dependent relationship between glucocorticoid use and bone loss was demonstrated in longitudinal studies in SLE. These findings have implications for daily clinical practice, because vitamin D insufficiency is highly frequent in SLE, antimalarials are regarded as 'anchor drugs' for therapy and the majority of patients with SLE are on chronic glucocorticoid treatment. PMID- 26557386 TI - Sleep Disorders, Obesity, Hypertension, and Cardiovascular Risk. PMID- 26557385 TI - Identification of Iron Homeostasis Genes Dysregulation Potentially Involved in Retinopathy of Prematurity Pathogenicity by Microarray Analysis. AB - Retinopathy of prematurity (ROP) is a serious disease of preterm neonates and there are limited systematic studies of the molecular mechanisms underlying ROP. Therefore, here we performed global gene expression profiling in human fetal retinal microvascular endothelial cells (RMECs) under hypoxic conditions in vitro. Aborted fetuses were enrolled and primary RMECs were isolated from eyeballs. Cultivated cells were treated with CoCl2 to induce hypoxia. The dual color microarray approach was adopted to compare gene expression profiling between treated RMECs and the paired untreated control. The one-class algorithm in significance analysis of microarray (SAM) software was used to screen the differentially expressed genes (DEGs) and quantitative RT-PCR (qRT-PCR) was conducted to validate the results. Gene Ontology was employed for functional enrichment analysis. There were 326 DEGs between the hypoxia-induced group and untreated group. Of these genes, 198 were upregulated in hypoxic RMECs, while the other 128 hits were downregulated. In particular, genes in the iron ion homeostasis pathway were highly enriched under hypoxic conditions. Our study indicates that dysregulation of genes involved in iron homeostasis mediating oxidative damage may be responsible for the mechanisms underlying ROP. The "oxygen plus iron" hypothesis may improve our understanding of ROP pathogenesis. PMID- 26557384 TI - OsteoRheumatology: a new discipline? AB - This review summarises recent evidence about the interaction between bone, the immune system and cartilage in disabling conditions such as osteoarthritis, rheumatoid arthritis and spondyloarthritis. These topics have been recently discussed at the 'OsteoRheumatology' conference held in Genoa in October 2014. The meeting, at its 10th edition, has been conceived to bring together distinguished international experts in the fields of rheumatic and metabolic bone diseases with the aim of discussing emerging knowledge regarding the role of the bone tissue in rheumatic diseases. Moreover, this review focuses on new treatments based on underlying the pathophysiological processes in rheumatic diseases. Although, a number of issues still remain to be clarified, it seems quite clear that in clinical practice, as well as in basic and translational research, there is a need for more knowledge of the interactions between the cartilage, the immune system and the bone. In this context, 'OsteoRheumatology' represents a potential new discipline providing a greater insight into this interplay, in order to face the multifactorial and complex issues underlying common and disabling rheumatic diseases. PMID- 26557387 TI - Gastrojejunal Anastomosis Complications and Their Management after Laparoscopic Roux-en-Y Gastric Bypass. AB - BACKGROUND: Complications at the gastrojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass (LRYGB) are challenging in terms of diagnosis, therapy, and prevention. This study aims at identifying these complications and discussing their management. METHODS: Data of 228 patients who underwent a LRYGB between October 2008 and December 2011 were reviewed retrospectively to evaluate the frequency and treatment of complications such as stenoses, marginal ulcers, perforated marginal ulcers, or anastomotic leaks related to the operation. RESULTS: Follow-up information was available for 209 patients (91.7%) with a median follow-up of 38 months (range 24-62 months). Of these patients 16 patients (7.7%) experienced complications at the gastrojejunostomy. Four patients (1.9%) had stenoses and 12 patients (5.7%) marginal ulcers, one of them with perforation (0.5%). No anastomotic leaks were reported. One case with perforated ulcer and one with recurrent ulcers required surgical revision. CONCLUSION: Gastrojejunal anastomotic complications are frequent and occur within the first few days or up to several years after surgery. Stenoses or marginal ulcers are usually successfully treated nonoperatively. Laparoscopic repair, meanwhile, is an appropriate therapeutic option for perforated ulcers. PMID- 26557389 TI - Postinjury Neuroplasticity in Central Neural Networks. PMID- 26557388 TI - A Systematic Review Investigating the Presence of Inflammatory Synovitis in Hip and Knee Joint Replacement Surgery. AB - Synovial tissue can display an inflammatory response in the presence of OA. There is increasing interest to better understand the role of inflammation in OA, particularly with regard to those who require joint replacement. A systematic review of inflammatory synovitis in OA of literature databases was undertaken from their inception until October 14, 2014. Independent critical appraisal of each study was undertaken using the CASP appraisal tool. From a total of sixty six identified citations, twenty-three studies were deemed eligible for review. The studies presented moderate to strong methodological quality. Strong correlation was identified between histological and imaging synovitis severity. Correlation was weaker between clinical symptoms and imaging and/or histological synovitis severity. There was little consensus, with regard to expressed cytokines and chemokines at the different stages of OA disease progression. Few studies investigated the influence of inflammatory synovitis on the outcome of major joint replacement. Research into inflammatory synovitis in OA is an emerging field. Longitudinal studies applying proven imaging modalities, histological analysis, and longer follow-up are required in order to further define our understanding of the role of synovitis in the pathogenesis of OA and its effects on outcomes following major joint replacement. PMID- 26557390 TI - Vital Life-Threatening Hematoma after Implant Insertion in the Anterior Mandible: A Case Report and Review of the Literature. AB - Dental implant insertion is considered a safe and reliable surgical procedure and severe complications are seldom reported. However, we present a case of a 52-year old patient who attended our Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University Medical Center, Mainz, with spreading hematoma in the floor of the mouth and acute airway obstruction after insertion of a dental implant in the anterior mandible. The hematoma was removed and submentally drained by a silicon drainage. However, the progressive swelling of the tongue and the floor of the mouth necessitated a temporary tracheotomy for three days. The review of the literature summarizes guidelines for prevention and management of this life-threatening complication. PMID- 26557391 TI - Endocrown with Leucite-Reinforced Ceramic: Case of Restoration of Endodontically Treated Teeth. AB - A common problem encountered by dentists is the restorative treatment of nonvital teeth. When the pulp chamber presents appropriate conditions for retention, the endocrown is indicated. This monolithic, ceramic adhesive restoration is singularly used yet warrants wider recognition and use. The endocrown allows preservation of the tooth structure and is minimally invasive. Currently, this treatment option, of a core buildup and full coverage restoration, reduces tooth structure excessively. This treatment presents not only functional limitations but also aesthetic concerns. Recently, the VITA-PM9 system, a leucite-reinforced glass ceramic, has been increasingly used in a variety of clinical situations due to its satisfactory physical-mechanical and aesthetic properties. Therefore, the present study describes a case of surgical restoration of a nonvital tooth using the endocrown technique and the VITA-PM9. PMID- 26557392 TI - Full Mouth Oral Rehabilitation by Maxillary Implant Supported Hybrid Denture Employing a Fiber Reinforced Material Instead of Conventional PMMA. AB - Many people have life-long problems with their dentures, such as difficulties with speaking and eating, loose denture, and sore mouth syndrome. The evolution of dental implant supported prosthesis gives these patients normal healthy life for their functional and esthetic advantages. This case report presents the fabrication of maxillary implant supported hybrid prosthesis by using Nanofilled Composite (NFC) material in teeth construction to rehabilitate a complete denture wearer patient. PMID- 26557394 TI - Acute Systolic Heart Failure Associated with Complement-Mediated Hemolytic Uremic Syndrome. AB - Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS) is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease. PMID- 26557393 TI - Esophageal Cicatricial Pemphigoid as an Isolated Involvement Treated with Mycophenolate Mofetil. AB - Cicatricial pemphigoid (CP) is a rare blistering autoimmune disease. Esophageal involvement occurs in widespread disease and rarely appears as the only affected organ. We report a 67-year-old Caucasian female with esophageal dysphagia and weight loss. Several oral panendoscopies showed multiple exudative ulcerations with fibrin and webs in mid- and proximal esophagus and a peeling mucosa. There were no lesions in other organs. We established the diagnosis performing a direct immunofluorescence (DIF), demonstrating IgG3 and complement deposition along the basement membrane. As initial treatment the patient received prednisone 60 mg and 1 gr twice daily of mycophenolate mofetil (MMF) as a steroid-sparing agent due to its lower toxicity and its selective mechanism of action. Six months later there was a significant clinical improvement and the esophageal ulcerations had disappeared, developing cicatricial fibrous rings, although no stenosis was present. Four years later, the patient remains asymptomatic with a low maintenance dose of MMF. PMID- 26557395 TI - Mycobacterium sherrisii Lung Infection in a Brazilian Patient with Silicosis and a History of Pulmonary Tuberculosis. AB - Nontuberculous mycobacteria (NTM) diseases became relevant with the emergence and spread of HIV and are also related to lung infection in non-HIV individuals with structural lung diseases. Mycobacterium sherrisii is a NTM first characterized in 2004. Only a few cases have been reported. The aim of this case report is to describe the first detailed case of infection with M. sherrisii in a patient with silicosis and history of pulmonary tuberculosis. A 50-year-old HIV-negative white male, previous smoker, with silicosis and a history of treated pulmonary tuberculosis developed a worsening of cough and expectoration pattern, and two sputum samples were positive for acid-fast bacilli. Presumptive treatment for pulmonary tuberculosis was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol, but, at month 5 of treatment, despite correct medication intake and slight improvement of symptoms, sputum bacilloscopy remained positive. Sputum cultures were positive Mycobacterium sherrisii. Treatment regimen was altered to streptomycin (for 2 months), ethambutol, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. M. sherrisii should be considered a possible etiological agent of lung infections in patients with pneumoconiosis and history of tuberculosis. PMID- 26557396 TI - Fatal Injury of the Small Intestine during Retropubic Sling Placement. AB - We describe a case of injury of the small intestine in a patient who underwent placement of Align R retropubic urethral support system (BARD). Absence of characteristic symptoms of the bowel injury and peritonitis led to a rapid development of sepsis, multiple organ failure, and death. Although the placement of midurethral sling is a minimally invasive surgery, good diagnostic skills, proper evaluation of indications, safe performance of the procedure, and thorough postsurgical monitoring are paramount for safe and effective outcome of the surgery. PMID- 26557397 TI - Bilateral Serous Psammocarcinoma of Ovary: Rare Variant Low Grade Serous Carcinoma. AB - Serous psammocarcinoma is a rare variant of serous carcinoma arising from either ovary or peritoneum, characterized by massive psammoma body formation, low grade cytologic features, and invasiveness. Its clinical behavior is similar to serous borderline tumors with relatively favorable prognosis. We report herein a case of a 60-year-old postmenopausal woman who presented with abdominal distension. Contrast enhanced computed tomography (CECT) revealed calcified pelvic masses with ascites. Elevated serum CA-125 (970 U/mL) suggested malignant ovarian neoplasm. Patient underwent exploratory laparotomy with primary debulking surgery. Histopathology showed bilateral serous psammocarcinoma of ovary with invasive implants on omentum. Adjuvant chemotherapy was advised in view of advanced stage disease, although its benefits are poorly defined due to rarity of the tumor. However, patient opted out of it and is now on follow-up. PMID- 26557398 TI - Successful Delivery of Twin Pregnancy in Class U3b/C2/V1 Uterus by Bilateral Caesarean Section after Spontaneous Conception. AB - A case of a 19-year-old female with class U3b/C2/V1 uterus conceived a twin pregnancy with a fetus in each horn after spontaneous conception. She referred to our department with presentation of premature rupture of membranes, with a history of cesarean delivery of a single full term living fetus a year and a half before this delivery. Examination revealed two completely separate uterine horns with a fetus in each horn, two distinct externally rounded cervices, and a single vagina with a short nonobstructing vaginal septum in the upper part of the vagina. And as the appropriate mode of delivery is still unclear, each case should be managed as the condition requires, and in our case urgent bilateral caesarean sections were performed. PMID- 26557399 TI - Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant. AB - Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients. PMID- 26557400 TI - Ocular Inflammatory Myofibroblastic Tumor in the Left Eye with Phthisis Right Eye: A Rare Occurrence in a Child. AB - Inflammatory myofibroblastic tumor (IMT) is a benign pseudoneoplastic inflammatory condition with the potential for persistent local growth and recurrence that rarely affects the orbit. We report a very rare case of anterior orbital IMT in a child who presented with gradually progressive mass in left eye for 16 months. Ocular examination showed a cauliflower like exophytic mass at 360 degrees of the perilimbal area covering the entire cornea and obscuring the visualization of anterior and posterior segments. The right eye was phthisical. CT scan showed a lobulated exophytic soft tissue mass in the preseptal region and along the anterior portion of the left globe extending from medial canthus to the lateral canthus. Enucleation of the left eye was performed and the histopathological examination confirmed the diagnosis of IMT. This report aims to raise awareness about this rare ocular entity and emphasizes its early treatment as delay can result in loss of the eye. PMID- 26557401 TI - Multifocal ERG Guiding Therapy in a Case of Hydroxychloroquine Premaculopathy. AB - We report the case of a 28-year-old female treated for systemic lupus erythematosus with hydroxychloroquine (200 mg/day) for 11 years. She was visually asymptomatic, with normal fundus appearance, normal colour vision testing findings, 20/20 visual acuity in both eyes, and only mild central bilateral defects on 10-2 perimetry. Multifocal electroretinography (mfERG) showed low density values for ring 1 in both eyes. Because the patient had not previously responded to alternative treatments and in consultation with her physician, the hydroxychloroquine dose was reduced to 200 mg four days/week. Four serial mfERGs performed at 4, 18, 25, and 34 months after dose reduction showed a progressive improvement in the definition and density of the responses until they were normalized at the third mfERG (25 months after hydroxychloroquine dose reduction). The fourth and final mfERG at 34 months confirmed the recovery in both eyes. Perimetry defects were mostly normalized. These results demonstrate the importance of mfERG for the safe management of patients under long-term hydroxychloroquine treatment. PMID- 26557402 TI - A Case of Cerebral Vasculitis Associated with Ulcerative Colitis. AB - Ulcerative colitis (UC) is a chronic, debilitating condition characterized by inflammation of the colonic mucosa. It is regarded as a systemic inflammatory disorder that can affect a number of organ systems. Central nervous system disease associated with UC is a rare sequela of inflammatory bowel disease, occurring in less than 5% of cases. These manifestations include arterial and venous thrombosis, leukoencephalitis, seizures, and vasculitis. We present a case of a 61-year-old female with a two-year history of well-controlled ulcerative colitis, who developed altered mental status and weakness. On brain imaging, she was found to have cerebral lesions which were biopsied. Histopathology subsequently revealed coagulative necrosis and inflammation characteristic of vasculitis. Rheumatology serologies were negative, and the patient was started on steroids that dramatically improved her neurological function, with no residual deficits, and led to resolution of the brain lesions. PMID- 26557403 TI - A Case of Amyopathic Dermatomyositis with Pneumomediastinum and Subcutaneous Emphysema. AB - A 34-year-old man was admitted with dyspnea, cough, and fever. Thorax computed tomography revealed ground glass opacities and pneumomediastinum. The patient was diagnosed as amyopathic dermatomyositis due to skin lesions and radiological findings. Despite immunosuppressive treatment clinical deterioration and radiological progression were observed and the patient died because of severe hypoxemic respiratory failure. The patient presented with extremely rare occurrence of pneumomediastinum and subcutaneous emphysema in amyopathic dermatomyositis with a poor prognosis. PMID- 26557404 TI - Chemistry of Medicinal Plants, Foods, and Natural Products 2015. PMID- 26557406 TI - Communication of Bad News to Patients: Is Honesty the Best Policy? PMID- 26557405 TI - Core Muscle Activity, Exercise Preference, and Perceived Exertion during Core Exercise with Elastic Resistance versus Machine. AB - Objectives. To investigate core muscle activity, exercise preferences, and perceived exertion during two selected core exercises performed with elastic resistance versus a conventional training machine. Methods. 17 untrained men aged 26-67 years participated in surface electromyography (EMG) measurements of five core muscles during torso-twists performed from left to right with elastic resistance and in the machine, respectively. The order of the exercises was randomized and each exercise consisted of 3 repetitions performed at a 10 RM load. EMG amplitude was normalized (nEMG) to maximum voluntary isometric contraction (MVC). Results. A higher right erector spinae activity in the elastic exercise compared with the machine exercise (50% [95% CI 36-64] versus 32% [95% CI 18-46] nEMG) was found. By contrast, the machine exercise, compared with the elastic exercise, showed higher left external oblique activity (77% [95% CI 64 90] versus 54% [95% CI 40-67] nEMG). For the rectus abdominis, right external oblique, and left erector spinae muscles there were no significant differences. Furthermore, 76% preferred the torso-twist with elastic resistance over the machine exercise. Perceived exertion (Borg CR10) was not significantly different between machine (5.8 [95% CI 4.88-6.72]) and elastic exercise (5.7 [95% CI 4.81 6.59]). Conclusion. Torso-twists using elastic resistance showed higher activity of the erector spinae, whereas torso-twist in the machine resulted in higher activity of the external oblique. For the remaining core muscles the two training modalities induced similar muscular activation. In spite of similar perceived exertion the majority of the participants preferred the exercise using elastic resistance. PMID- 26557407 TI - The Consequences of a BRCA Mutation in Women. PMID- 26557408 TI - The Toxicity and Benefit of Various Dosing Strategies for Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma. AB - Interleukin-2 (IL-2) therapy has been used with success in curing meta-static renal cell carcinoma and melanoma in a small minority of patients. However, the benefits can be accompanied by severe toxicity. This review of the literature discusses varying doses of IL-2 and their associated re-sponse rates and the toxicities associated with treatment. The review also explores the maximally beneficial dose with the most tolerable side effects. Although the higher-dose regimens with a more frequent dosing schedule produce higher-grade toxicity, they were found to deliver the most durable and complete responses. It is recommended to use a higher-dose regimen (720,000 IU/kg every 8 hours for a maximum of 15 doses) and provide sup-portive care for toxicity, so patients can have maximal benefit from therapy. PMID- 26557409 TI - Hypnosis for the Management of Anticipatory Nausea and Vomiting. AB - CASE STUDYBJ is a 34-year-old woman who was diagnosed with metastatic breast cancer. She was treated with surgical removal of the primary tumor and sentinel node biopsy. Following surgery, she received chemotherapy. She was given antiemetic therapy prior to and immediately following chemotherapy. She began to experience significant and persistent nausea with intermittent episodes of vomiting after the second cycle of chemotherapy. She completed her chemotherapy but still experienced nausea and vomiting in response to several cues, such as smelling food cooking and going to the hospital. Her nausea and vomiting resulted in segregation from her family during meal time, which negatively impacted her quality of life. A hypnosis consultation was requested, and BJ was cooperative. She reported feeling very nauseated at the time of the interview. Hypnosis was discussed; her questions were answered, and the potential risks and benefits of hypnosis were reviewed. She agreed that she would like to try hypnosis. A hypnosis assessment was conducted and revealed that she had a history of profound motion sickness and severe, chronic childhood trauma associated with feelings of anxiety and hypervigilance. The therapeutic suggestions that were used with BJ included hypnotic suggestions for relaxation and removal of discomfort. A metaphor describing the central processing of the anticipatory nausea and vomiting as a thermostat that could be adjusted to reduce and eliminate the sensation was used to suggest that she could control her perceptions and in turn control the nausea. Posthypnotic suggestions included that at the earliest awareness of discomfort, rubbing the throat would eliminate that discomfort, and cooking aromas would be transformed into her favorite fragrance. Reversal went smoothly, and BJ reported satisfaction with the experience. BJ experienced significant reduction in symptoms after the first session. She had two more sessions, at which time she was able to eat with her family and go to the clinic without discomfort. She was provided a CD with a recording of her hypnosis script to reinforce the face-to-face intervention. She continues to be symptom-free 3 months after treatment with hypnosis. PMID- 26557410 TI - Pembrolizumab: First in Class for Treatment of Metastatic Melanoma. PMID- 26557411 TI - Evaluating a Sexual Health Patient Education Resource. AB - This article shares the findings of an evaluation of a patient teaching resource for sexual health entitled Everything Nobody Tells You About Cancer Treatment and Your Sex Life: From A to Z, which was accomplished through systematic conceptualization, construction, and evaluation with women diagnosed with breast or gynecologic cancer. This resource, which has evolved from patient-focused research and has been tested in the clinical setting, can be used in patient education and support. Oncology professionals are committed to addressing quality of-life concerns for patients across the trajectory of illness. Sexuality is a key concern for patients and impacts relationships and overall quality of life. Through careful assessment, patient education, and support, clinicians can ensure that sexuality is respected as an essential part of patient-centered care. PMID- 26557412 TI - Significance of Human Papillomavirus in Head and Neck Cancers. PMID- 26557413 TI - The Use of Calcium and Magnesium to Prevent Neurotoxicity in Patients Receiving Oxaliplatin. PMID- 26557414 TI - Calcium and Magnesium for Oxaliplatin-Induced Neurotoxicity: Issues in Study Design, Measurement, and Analysis. PMID- 26557416 TI - Basal Cell Carcinoma: What You Need to Know. PMID- 26557415 TI - Writing a Successful Grant: Tips and Tools. PMID- 26557418 TI - Isolation and characterization of 10 polymorphic microsatellite loci for the endangered Galapagos-endemic whitespotted sandbass (Paralabrax albomaculatus). AB - The white-spotted sandbass (Paralabrax albomaculatus) is a commercially important species in the Galapagos Marine Reserve, but is classified as endangered in the IUCN Red List. For this study, 10 microsatellite loci were isolated and characterized using Illumina paired-end sequencing. These loci can be used for genetic studies of population structure and connectivity to aid in the management of the white-spotted sandbass and other closely-related species. The 10 characterized loci were polymorphic, with 11-49 alleles per locus, and observed heterozygosity ranged from 0.575 to 0.964. This set of markers is the first to be developed for this species. PMID- 26557417 TI - Reengineering Human Bruch's Membrane Increases Rod Outer Segment Phagocytosis by Human Retinal Pigment Epithelium. AB - PURPOSE: We have shown previously that Bruch's membrane (BM) aging decreases retinal pigment epithelium (RPE) phagocytosis. Herein, we determine the effects of BM reengineering on RPE phagocytosis. METHODS: BM explants were dissected from young and old donor eyes. Some old BM explants were reengineered by cleaning with Triton X-100 and/or coating with extracellular matrix (ECM) ligands. ARPE-19 cell derived ECM (ARPE-ECM) modified ("aged") by sodium nitrite was subjected to similar treatments. ARPE-19 cells were then cultured to confluence onto the different surfaces. Fluorescently-labeled bovine rod outer segments (ROS) were fed to cells with or without alphaVbeta5 integrin antibody. Image acquisition and phagocytosis quantification was performed by fluorescence microscopy and ImageJ analysis. RESULTS: Cleaning old donor-derived BM with detergent does not increase the uptake of ROS, but a combination of cleaning and coating with ECM ligands significantly increases RPE phagocytosis (54.9 +/- 6.2 vs. 83.5 +/- 6.5 arbitrary units; P < 0.05) to levels closer to young donor BM (123.6 +/- 9.9 arbitrary units). Similar effects were observed on nitrite-modified ARPE-ECM subjected to the same treatments. Incubation of alphaVbeta5 blocking antibody with ROS significantly decreased RPE phagocytosis. CONCLUSIONS: The detrimental effects of aging BM on RPE phagocytosis can be reversed by reengineering the BM surface with detergent cleaning and recoating with ECM ligands. TRANSLATION RELEVANCE: These results demonstrate that the therapeutic success of transplanted RPE cells may require, at least in part, reengineering of diseased BM to make it a more suitable environment for attachment, survival and proper functioning of the RPE. PMID- 26557419 TI - The prevalence and anatomical characteristics of the accessory head of the flexor pollicis longus muscle: a meta-analysis. AB - Background and Objectives. The accessory head of the flexor pollicis longus muscle (AHFPL), also known as the Gantzer's muscle, was first described in 1813. The prevalence rates of an AHFPL significantly vary between studies, and no consensus has been reached on the numerous variations reported in its origin, innervation, and relationships to the Anterior Interosseous Nerve (AIN) and the Median Nerve (MN). The aim of our study was to determine the true prevalence of AHFPL and to study its associated anatomical characteristics. Methods. A search of the major electronic databases PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science was performed to identify all articles reporting data on the prevalence of AHPFL in the population. No date or language restriction was set. Additionally, an extensive search of the references of all relevant articles was performed. Data on the prevalence of the AHFPL in upper limbs and its anatomical characteristics and relationships including origin, insertion, innervation, and position was extracted and pooled into a meta-analysis using MetaXL version 2.0. Results. A total of 24 cadaveric studies (n = 2,358 upper limb) were included in the meta-analysis. The pooled prevalence of an AHFPL was 44.2% (95% CI [0.347 0.540]). An AHFPL was found more commonly in men than in women (41.1% vs. 24.1%), and was slightly more prevalent on the right side than on the left side (52.8% vs. 45.2%). The most common origin of the AHFPL was from the medial epicondyle of the humerus with a pooled prevalence of 43.6% (95% CI [0.166-0.521]). In most cases, the AHFPL inserted into the flexor pollicis longus muscle (94.6%, 95% CI [0.731-1.0]) and was innervated by the AIN (97.3%, 95% CI [0.924-0.993]). Conclusion. The AHFPL should be considered as more a part of normal anatomy than an anatomical variant. The variability in its anatomical characteristics, and its potential to cause compression of the AIN and MN, must be taken into account by physicians to avoid iatrogenic injury during decompression procedures and to aid in the diagnosis and treatment of Anterior Interosseous Nerve Syndrome. PMID- 26557420 TI - Measuring the well-being of health care professionals in the Punjab: a psychometric evaluation of the Warwick-Edinburgh Mental Well-being Scale in a Pakistani population. AB - Background. There is growing awareness of the public health importance of mental well-being both in the general population and in specific groups. The well-being of health professionals is likely to influence the quality of the care they deliver. This study was carried out to examine the well-being of Pakistani healthcare professionals, and to evaluate the psychometric performance of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in this population. Methods. A cross-sectional survey was carried out from June, 2013 to December, 2014 among 1,271 Pakistani health care providers (HCPs) working in seven different cities in Punjab province, Pakistan, to examine the acceptability, internal consistency, test-retest reliability and content and construct validity of the English version of the WEMWBS in a Pakistani population sample. All data were analyzed in SPSS v. 21. Results. Our analysis demonstrated unidimensional construct validity, high internal consistency (0.89) and test-retest reliability, good validity and easy readability of WEMWBS in our sample of Pakistani HCPs. The mean WEMWBS score was 48.1 (SD 9.4), which is lower than in the general population in other countries. Male HCPs scored significantly higher on the WEMWBS than their female counterparts (P < 0.05), and older respondents had higher scores. Conclusion. The WEMWBS appears acceptable for use in Pakistani HCPs, and findings from this study verify its validity and internal consistency for this population sample. Our respondents had lower well-being scores than those reported in general population surveys in the UK. PMID- 26557421 TI - Risk factors and prognosis of hypoalbuminemia in surgical septic patients. AB - The aim of this study was to investigate the risk factors of hypoalbuminemia and effects of different albumin levels on the prognosis of surgical septic patients. We preformed a retrospective clinical study including 135 adult patients from September 2011 to June 2014. The albumin levels and severity markers were recorded during the first 48 h after enrollment, and logistic regression analyses were used to determine the risk factors. The outcomes of patients with different albumin levels were also compared. The acute physiology and chronic health evaluation II (APACHE II) score (OR 1.786, 95% CI [1.379-2.314], P < 0.001), C reactive protein (CRP) (OR 1.016, 95% CI [1.005-1.027], P = 0.005), and blood lactate (OR 1.764, 95% CI [1.141-2.726], P = 0.011) were established as the independent risk factors of hypoalbuminemia in patients with surgical sepsis. The severity markers and outcomes of patients with albumin levels <=20 g/L were significantly worse than that of 21-25 g/L and >=26 g/L, whereas the latter two groups had similar prognosis. Every 1 g/L decrease of albumin level below the optimal cut-off (23 g/L) was associated with a 19.4% increase in hospital mortality and a 28.7% increase in the incidence of multiple organ dysfunction syndrome. In conclusion, APACHE II score (>=14.5), CRP (>=34.25 mg/L), and blood lactate (>=.35 mmol/L) were established as the independent risk factors of hypoalbuminemia in the early stage of surgical sepsis. Patients with baseline albumin level <=20 g/L had worse prognosis than that of albumin level >=21 g/L. Albumin levels were negatively correlated the prognosis of surgical sepsis when below about 23 g/L. PMID- 26557422 TI - Successful survival, growth, and reproductive potential of quagga mussels in low calcium lake water: is there uncertainty of establishment risk? AB - The risk of quagga mussel (Dreissena rostriformis bugensis Andrusov 1897) establishment into water-bodies of the western US has expanded the geographic concern regarding the ecological and economic impacts this species will have in aquatic ecosystems. Thresholds based on calcium concentrations, an element critical for mussel growth and physiology, have been used as a primary predictor of quagga mussel establishment success to aid management decisions. We evaluated the invasion potential of quagga mussels in low calcium waters using laboratory experiments to compare the survival, growth and reproductive potential of adult mussels held for 90 days at low (9 and 12 ppm), moderate (15 to 32 ppm) and high (72 ppm) calcium water concentrations. In conjunction with adult experiments, veliger stage survival, growth and settlement were evaluated under similar low, moderate, and high calcium water treatments. Adult mussels survived, grew and showed reproductive potential in low calcium water (12 ppm). Veligers were also able to survive, grow and settle in low calcium water. Higher levels of natural seston biomass appeared to improve adult mussel life history performance in low calcium water. Survival curve analysis predicted that 99% adult mortality could occur in <170 days at 9 ppm and 12 ppm, however water with >15 ppm could have adults surviving more than a year. The results from these bioassays provide further evidence that quagga mussels have higher risk of establishment in low calcium lakes if habitats exist that have slightly elevated calcium. These results should help emphasize the vulnerability of water-body in the 12 to 15 ppm calcium range that could potentially be at risk of establishing sustainable quagga mussel populations. Furthermore, these results provide insights into the uncertainty of using a single parameter in assigning establishment risk given the complexity of variables in specific water-bodies that influence life history performance of introduced species. PMID- 26557423 TI - Pore size is a critical parameter for obtaining sustained protein release from electrochemically synthesized mesoporous silicon microparticles. AB - Mesoporous silicon has become a material of high interest for drug delivery due to its outstanding internal surface area and inherent biodegradability. We have previously reported the preparation of mesoporous silicon microparticles (MS-MPs) synthesized by an advantageous electrochemical method, and showed that due to their inner structure they can adsorb proteins in amounts exceeding the mass of the carrier itself. Protein release from these MS-MPs showed low burst effect and fast delivery kinetics with complete release in a few hours. In this work, we explored if tailoring the size of the inner pores of the particles would retard the protein release process. To address this hypothesis, three new MS-MPs prototypes were prepared by electrochemical synthesis, and the resulting carriers were characterized for morphology, particle size, and pore structure. All MS-MP prototypes had 90 um mean particle size, but depending on the current density applied for synthesis, pore size changed between 5 and 13 nm. The model protein alpha-chymotrypsinogen was loaded into MS-MPs by adsorption and solvent evaporation. In the subsequent release experiments, no burst release of the protein was detected for any prototype. However, prototypes with larger pores (>10 nm) reached 100% release in 24-48 h, whereas prototypes with small mesopores (<6 nm) still retained most of their cargo after 96 h. MS-MPs with ~6 nm pores were loaded with the osteogenic factor BMP7, and sustained release of this protein for up to two weeks was achieved. In conclusion, our results confirm that tailoring pore size can modify protein release from MS-MPs, and that prototypes with potential therapeutic utility for regional delivery of osteogenic factors can be prepared by convenient techniques. PMID- 26557424 TI - Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy. AB - In spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critical signaling pathways related to diabetic nephropathy. GSE1009 dataset was downloaded from Gene Expression Omnibus database and the gene expression profile of glomeruli from diabetic nephropathy patients and those from healthy individuals were compared. The protein-protein interaction network for differentially expressed genes was constructed and enriched. In addition, topology of the network was analyzed to identify the genes with high centrality parameters and then pathway enrichment analysis was performed. We found 49 genes to be variably expressed between the two groups. The network of these genes had few interactions so it was enriched and a network with 137 nodes was constructed. Based on different parameters, 34 nodes were considered to have high centrality in this network. Pathway enrichment analysis with these central genes identified 62 inter-connected signaling pathways related to diabetic nephropathy. Interestingly, the central nodes were more informative for pathway enrichment analysis compared to all network nodes and also 49 differentially expressed genes. In conclusion, we here show that central nodes in protein interaction networks tend to be present in pathways that co-occur in a biological state. Also, this study suggests a computational method for inferring underlying mechanisms of complex disorders from raw high-throughput data. PMID- 26557425 TI - Association among smoking, depression, and anxiety: findings from a representative sample of Korean adolescents. AB - This study investigated the relationship between smoking and depression and anxiety using data from a nationwide survey representing Korean adolescents. Subjects were 6,489 adolescents in middle and high school (age 13-18) who had participated in the 2011 Korean Study of Promotion Policies on Children and Adolescents-Mental Health (KSPCAM). Daily smoking number of times for current smokers was classified as 1-2 times, 2-4 times and over 5 times. The odds ratio for the statistical test was presented using hierarchical logistic regression. When adjusted for covariates (gender, age, household economy, type of residing city, type of school, school record, satisfaction with school life, subjective health status, satisfaction with relationship with parents, and drinking experience), smokers more significantly likely to have depression (OR = 1.27, 95% CI [1.02-1.57]), and anxiety (OR = 1.49, 95% CI [1.14-1.96]) than non-smokers (p < 0.05). In addition, adolescents who smoke more than 5 cigarettes a day were 1.5 times more likely to have depression (OR = 1.48, 95% CI [1.13-1.92]) and anxiety (OR = 1.49, 95% CI [1.07-2.08]) than those who do not smoke. Smoking in adolescence was found to be significantly related with depression and anxiety. To promote the mental health of adolescents, effective smoking cessation programs are required. PMID- 26557427 TI - Dispersal and metapopulation stability. AB - Metapopulation dynamics are jointly regulated by local and spatial factors. These factors may affect the dynamics of local populations and of the entire metapopulation differently. Previous studies have shown that dispersal can stabilize local populations; however, as dispersal also tends to increase spatial synchrony, its net effect on metapopulation stability has been controversial. Here we present a simple metapopulation model to study how dispersal, in interaction with other spatial and local processes, affects the temporal variability of metapopulations in a stochastic environment. Our results show that in homogeneous metapopulations, the local stabilizing and spatial synchronizing effects of dispersal cancel each other out, such that dispersal has no effect on metapopulation variability. This result is robust to moderate heterogeneities in local and spatial parameters. When local and spatial dynamics exhibit high heterogeneities, however, dispersal can either stabilize or destabilize metapopulation dynamics through various mechanisms. Our findings have important theoretical and practical implications. We show that dispersal functions as a form of spatial intraspecific mutualism in metapopulation dynamics and that its effect on metapopulation stability is opposite to that of interspecific competition on local community stability. Our results also suggest that conservation corridors should be designed with appreciation of spatial heterogeneities in population dynamics in order to maximize metapopulation stability. PMID- 26557426 TI - Investigation into the effects of antioxidant-rich extract of Tamarindus indica leaf on antioxidant enzyme activities, oxidative stress and gene expression profiles in HepG2 cells. AB - The leaf extract of Tamarindus indica L. (T. indica) had been reported to possess high phenolic content and showed high antioxidant activities. In this study, the effects of the antioxidant-rich leaf extract of the T. indica on lipid peroxidation, antioxidant enzyme activities, H2O2-induced ROS production and gene expression patterns were investigated in liver HepG2 cells. Lipid peroxidation and ROS production were inhibited and the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was enhanced when the cells were treated with the antioxidant-rich leaf extract. cDNA microarray analysis revealed that 207 genes were significantly regulated by at least 1.5 fold (p < 0.05) in cells treated with the antioxidant-rich leaf extract. The expression of KNG1, SERPINC1, SERPIND1, SERPINE1, FGG, FGA, MVK, DHCR24, CYP24A1, ALDH6A1, EPHX1 and LEAP2 were amongst the highly regulated. When the significantly regulated genes were analyzed using Ingenuity Pathway Analysis software, "Lipid Metabolism, Small Molecule Biochemistry, Hematological Disease" was the top biological network affected by the leaf extract, with a score of 36. The top predicted canonical pathway affected by the leaf extract was the coagulation system (P < 2.80 * 10(-6)) followed by the superpathway of cholesterol biosynthesis (P < 2.17 * 10(-4)), intrinsic prothrombin pathway (P < 2.92 * 10(-4)), Immune Protection/Antimicrobial Response (P < 2.28 * 10(-3)) and xenobiotic metabolism signaling (P < 2.41 * 10(-3)). The antioxidant-rich leaf extract of T. indica also altered the expression of proteins that are involved in the Coagulation System and the Intrinsic Prothrombin Activation Pathway (KNG1, SERPINE1, FGG), Superpathway of Cholesterol Biosynthesis (MVK), Immune protection/antimicrobial response (IFNGR1, LEAP2, ANXA3 and MX1) and Xenobiotic Metabolism Signaling (ALDH6A1, ADH6). In conclusion, the antioxidant-rich leaf extract of T. indica inhibited lipid peroxidation and ROS production, enhanced antioxidant enzyme activities and significantly regulated the expression of genes and proteins involved with consequential impact on the coagulation system, cholesterol biosynthesis, xenobiotic metabolism signaling and antimicrobial response. PMID- 26557428 TI - Effect of shampoo, conditioner and permanent waving on the molecular structure of human hair. AB - The hair is a filamentous biomaterial consisting of the cuticle, the cortex and the medulla, all held together by the cell membrane complex. The cortex mostly consists of helical keratin proteins that spiral together to form coiled-coil dimers, intermediate filaments, micro-fibrils and macro-fibrils. We used X-ray diffraction to study hair structure on the molecular level, at length scales between ~3-90 A, in hopes of developing a diagnostic method for diseases affecting hair structure allowing for fast and noninvasive screening. However, such an approach can only be successful if common hair treatments do not affect molecular hair structure. We found that a single use of shampoo and conditioner has no effect on packing of keratin molecules, structure of the intermediate filaments or internal lipid composition of the membrane complex. Permanent waving treatments are known to break and reform disulfide linkages in the hair. Single application of a perming product was found to deeply penetrate the hair and reduce the number of keratin coiled-coils and change the structure of the intermediate filaments. Signals related to the coiled-coil structure of the alpha keratin molecules at 5 and 9.5 A were found to be decreased while a signal associated with the organization of the intermediate filaments at 47 A was significantly elevated in permed hair. Both these observations are related to breaking of the bonds between two coiled-coil keratin dimers. PMID- 26557429 TI - Effects of mediated social touch on affective experiences and trust. AB - This study investigated whether communication via mediated hand pressure during a remotely shared experience (watching an amusing video) can (1) enhance recovery from sadness, (2) enhance the affective quality of the experience, and (3) increase trust towards the communication partner. Thereto participants first watched a sad movie clip to elicit sadness, followed by a funny one to stimulate recovery from sadness. While watching the funny clip they signaled a hypothetical fellow participant every time they felt amused. In the experimental condition the participants responded by pressing a hand-held two-way mediated touch device (a Frebble), which also provided haptic feedback via simulated hand squeezes. In the control condition they responded by pressing a button and they received abstract visual feedback. Objective (heart rate, galvanic skin conductance, number and duration of joystick or Frebble presses) and subjective (questionnaires) data were collected to assess the emotional reactions of the participants. The subjective measurements confirmed that the sad movie successfully induced sadness while the funny movie indeed evoked more positive feelings. Although their ranking agreed with the subjective measurements, the physiological measurements confirmed this conclusion only for the funny movie. The results show that recovery from movie induced sadness, the affective experience of the amusing movie, and trust towards the communication partner did not differ between both experimental conditions. Hence, feedback via mediated hand touching did not enhance either of these factors compared to visual feedback. Further analysis of the data showed that participants scoring low on Extraversion (i.e., persons that are more introvert) or low on Touch Receptivity (i.e., persons who do not like to be touched by others) felt better understood by their communication partner when receiving mediated touch feedback instead of visual feedback, while the opposite was found for participants scoring high on these factors. The implications of these results for further research are discussed, and some suggestions for follow up experiments are presented. PMID- 26557430 TI - Identification of limiting climatic and geographical variables for the distribution of the tortoise Chelonoidis chilensis (Testudinidae): a baseline for conservation actions. AB - Background. Just as for most other tortoise species, the once common Chaco tortoise, Chelonoidis chilensis (Testudinidae), is under constant threat across it distribution in Argentina, Bolivia and Paraguay. Despite initial qualitative description of the species distribution and further individual reports of new locations for the species, there is no description of the species distribution in probabilistic terms. With this work we aim to produce an updated predictive distribution map for C. chilensis to serve as a baseline management tool for directed strategic conservation planning. Methods. We fitted a spatially expanded logistic regression model within the Bayesian framework that accounts for uncertainty on presence-only and generated pseudo-absence data into the parameter estimates. We contrast the results with reported data for the national networks of protected areas to assess the inclusion of the species in area-based conservation strategies. Results. We obtained maps with predictions of the occurrence of the species and reported the model's uncertainty spatially. The model suggests that potential suitable habitats for the species are continuous across Argentina, West Paraguay and South Bolivia, considering the variables, the scale and the resolution used. The main limiting variables were temperature related variables, and precipitation in the reproductive period. Discussion. Given the alarming low density and coverage of protected areas over the distribution area of C. chilensis, the map produced provides a baseline to identify areas where directed strategic conservation management actions would be more efficient for this and other associated species. PMID- 26557431 TI - Unraveling mysteries of personal performance style; biomechanics of left-hand position changes (shifting) in violin performance. AB - Instrumental music performance ranks among the most complex of learned human behaviors, requiring development of highly nuanced powers of sensory and neural discrimination, intricate motor skills, and adaptive abilities in a temporal activity. Teaching, learning and performing on the violin generally occur within musico-cultural parameters most often transmitted through aural traditions that include both verbal instruction and performance modeling. In most parts of the world, violin is taught in a manner virtually indistinguishable from that used 200 years ago. The current study uses methods from movement science to examine the "how" and "what" of left-hand position changes (shifting), a movement skill essential during violin performance. In doing so, it begins a discussion of artistic individualization in terms of anthropometry, the performer-instrument interface, and the strategic use of motor behaviors. Results based on 540 shifting samples, a case series of 6 professional-level violinists, showed that some elements of the skill were individualized in surprising ways while others were explainable by anthropometry, ergonomics and entrainment. Remarkably, results demonstrated each violinist to have developed an individualized pacing for shifts, a feature that should influence timing effects and prove foundational to aesthetic outcomes during performance. Such results underpin the potential for scientific methodologies to unravel mysteries of performance that are associated with a performer's personal artistic style. PMID- 26557432 TI - Spider crabs of the Western Atlantic with special reference to fossil and some modern Mithracidae. AB - Spider crabs (Majoidea) are well-known from modern oceans and are also common in the western part of the Atlantic Ocean. When spider crabs appeared in the Western Atlantic in deep time, and when they became diverse, hinges on their fossil record. By reviewing their fossil record, we show that (1) spider crabs first appeared in the Western Atlantic in the Late Cretaceous, (2) they became common since the Miocene, and (3) most species and genera are found in the Caribbean region from the Miocene onwards. Furthermore, taxonomic work on some modern and fossil Mithracidae, a family that might have originated in the Western Atlantic, was conducted. Specifically, Maguimithrax gen. nov. is erected to accommodate the extant species Damithrax spinosissimus, while Damithrax cf. pleuracanthus is recognized for the first time from the fossil record (late Pliocene-early Pleistocene, Florida, USA). Furthermore, two new species are described from the lower Miocene coral-associated limestones of Jamaica (Mithrax arawakum sp. nov. and Nemausa windsorae sp. nov.). Spurred by a recent revision of the subfamily, two known species from the same deposits are refigured and transferred to new genera: Mithrax donovani to Nemausa, and Mithrax unguis to Damithrax. The diverse assemblage of decapods from these coral-associated limestones underlines the importance of reefs for the abundance and diversity of decapods in deep time. Finally, we quantitatively show that these crabs possess allometric growth in that length/width ratios drop as specimens grow, a factor that is not always taken into account while describing and comparing among taxa. PMID- 26557433 TI - Home range and use of diurnal shelters by the Etendeka round-eared sengi, a newly discovered Namibian endemic desert mammal. AB - To understand habitat use by the newly described Etendeka round-eared sengi (Macroscelides micus) in northwestern Namibia, we radio-tracked five individuals for nearly a month. Home ranges (100% convex polygons) in the rocky desert habitat were remarkably large (mean 14.9 ha) when compared to sengi species in more mesic habitats (<1.5 ha). The activity pattern of M. micus was strictly nocturnal, which contrasts to the normal diurnal or crepuscular activity of other sengis. The day shelters of M. micus were under single rocks and they likely were occupied by single sengis. One tagged sengi used 22 different day shelters during the study. On average, only 7% of the day shelters were used more than once by the five tagged sengis. The shelters were also unusual for a small mammal in that they were unmodified in terms of excavation or nesting material. Shelter entrances were significantly oriented to face south by south west (average 193 degrees ), away from the angle of the prevailing midday sun. This suggests that solar radiation is probably an important aspect of M. micus thermal ecology, similar to other sengis. Compared to published data on other sengis, M. micus generally conforms to the unique sengi adaptive syndrome, but with modifications related to its hyper-arid habitat. PMID- 26557434 TI - Relationship of central incisor implant placement to the ridge configuration anterior to the nasopalatine canal in dentate and partially edentulous individuals: a comparative study. AB - Background. The aims of this study were to investigate the ridge contour anterior to the nasopalatine canal, and the difference between the incidences of the nasopalatine canal perforation in dentate and partially edentulous patients by cone-beam computed tomography. Methods. Cone-beam computed tomography scan images from 72 patients were selected from database and divided into dentate and partially edentulous groups. The configuration of the ridge anterior to the canal including palatal concavity depth, palatal concavity height, palatal concavity angle, bone height coronal to the incisive foramen, and bone width anterior to the canal was measured. A virtual implant placement procedure was used, and the incidences of perforation were evaluated after implant placement in the cingulum position with the long axis along with the designed crown. Results. Comparing with variable values from dentate patients, the palatal concavity depth and angle were greater by 0.9 mm and 4 degrees , and bone height was shorter by 1.1 mm in partially edentulous patients, respectively. Bone width in edentulous patients was narrower than in dentate patients by 1.2 mm at incisive foramen level and 0.9 mm at 8 mm subcrestal level, respectively. After 72 virtual cylindrical implants (4.1 * 12 mm) were placed, a total of 12 sites (16.7%) showed a perforation and three-fourths occurred in partially edentulous patients. After replacing with 72 tapered implants (4.3 * 13 mm), only 6 implants (8.3%) broke into the canal in the partially edentulous patient group. Conclusions. The nasopalatine canal may get close to the implant site and the bone width anterior to the canal decreases after the central incisor extraction. The incidence of nasopalatine canal perforation may occur more commonly during delayed implant placement in central incisor missing patients. PMID- 26557435 TI - Overcoming pain thresholds with multilevel models-an example using quantitative sensory testing (QST) data. AB - The assessment of somatosensory function is a cornerstone of research and clinical practice in neurology. Recent initiatives have developed novel protocols for quantitative sensory testing (QST). Application of these methods led to intriguing findings, such as the presence lower pain-thresholds in healthy children compared to healthy adolescents. In this article, we (re-) introduce the basic concepts of signal detection theory (SDT) as a method to investigate such differences in somatosensory function in detail. SDT describes participants' responses according to two parameters, sensitivity and response-bias. Sensitivity refers to individuals' ability to discriminate between painful and non-painful stimulations. Response-bias refers to individuals' criterion for giving a "painful" response. We describe how multilevel models can be used to estimate these parameters and to overcome central critiques of these methods. To provide an example we apply these methods to data from the mechanical pain sensitivity test of the QST protocol. The results show that adolescents are more sensitive to mechanical pain and contradict the idea that younger children simply use more lenient criteria to report pain. Overall, we hope that the wider use of multilevel modeling to describe somatosensory functioning may advance neurology research and practice. PMID- 26557436 TI - Chewed out: an experimental link between food material properties and repetitive loading of the masticatory apparatus in mammals. AB - Using a model organism (rabbits) that resembles a number of mammalian herbivores in key aspects of its chewing behaviors, we examined how variation in dietary mechanical properties affects food breakdown during mastication. Such data have implications for understanding phenotypic variation in the mammalian feeding apparatus, particularly with respect to linking jaw form to diet-induced repetitive loading. Results indicate that chewing frequency (chews/s) is independent of food properties, whereas chewing investment (chews/g) and chewing duration(s), which are proportional to repetitive loading of the jaws, are positively related to food stiffness and toughness. In comparisons of displacement-limited and stress-limited fragmentation indices, which respectively characterize the intraoral breakdown of tough and stiff foods, increases in chewing investment and duration are linked solely to stiffness. This suggests that stiffer foods engender higher peak loads and increased cyclical loading. Our findings challenge conventional wisdom by demonstrating that toughness does not, by itself, underlie increases in cyclical loading and loading duration. Instead, tough foods may be associated with such jaw-loading patterns because they must be processed in greater volumes owing to their lower nutritive quality and for longer periods of time to increase oral exposure to salivary chemicals. PMID- 26557437 TI - Removal of concentrated sulfamethazine by acclimatized aerobic sludge and possible metabolic products. AB - This article examined the biological removal of high concentrated sulfamethazine (SMZ) antibiotics by the acclimatized activated sludge in lab-scale SBRs system. The removal of SMZ was characterized by a quick adsorption and a slow process of biodegradation. The adsorption capacity of activated sludge for SMZ was 44 and 47 ug SMZ/g SS, respectively, with the initial SMZ concentrations of 1 and 2 mg/L. The adsorption process fitted pseudo-second-order kinetic model. In a series of batch studies, with the increase of initial SMZ concentration that were 1, 2, 3, 5, 7 and 9 mg/L, 56.0%, 51.3%, 42.2%, 29.5%, 25.0% and 20.8% of influent SMZ were biodegraded within 24 h of biological reaction, respectively. The Monod equation applied to simulate SMZ biodegradation had a good coefficient of determination (R2 > 0.99). Furthermore, the results of HPLC demonstrated that the SMZ was not completely removed by the acclimatized activated sludge. From the analysis of LC MS, 4 intermediates of SMZ biodegradation were identified: Sulfanilic Acid, 4 amino-N-(4,6-dimethyl-2 pyrimidin) benzene sulfonamide, N-(4,6-dimethyl-2 pyrimidin)-4-N-(benzene sulfonamide) benzene sulfonamide, N-(4,6-dimethyl-2 pyrimidin)-4-N-(4,6-dimethyl pyrimidine) benzene sulfonamide, and N-(4,6-dimethyl 2-pyrimidin)-4-N-(3-dimethyl-4-N sodium benzene sulfonamide) benzene sulfonamide. PMID- 26557438 TI - Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-kappaB1. AB - Hepatic stellate cells (HSCs) activation is essential to the pathogenesis of liver fibrosis. Exploring drugs targeting HSC activation is a promising anti fibrotic strategy. In the present study, we found suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, prominently suppressed the activation phenotype of a human hepatic stellate cell line-LX2. The production of collagen type I and alpha-smooth muscle actin (alpha-SMA) as well as the proliferation and migration of LX2 cells were significantly reduced by SAHA treatment. To determine the molecular mechanisms underlying this suppression, genome wild gene regulation by SAHA was determined by Affymetrix 1.0 human cDNA array. Upon SAHA treatment, the abundance of 331 genes was up-regulated and 173 genes was down-regulated in LX2 cells. Bioinformatic analyses of these altered genes highlighted the high mobility group box 1 (HMGB1) pathway was one of the most relevant pathways that contributed to SAHA induced suppression of HSCs activation. Further studies demonstrated the increased acetylation of intracellular HMGB1 in SAHA treated HSCs, and this increasing is most likely to be responsible for SAHA induced down regulation of nuclear factor kappa B1 (NF-kappaB1) and is one of the main underlying mechanisms for the therapeutic effect of SAHA for liver fibrosis. PMID- 26557439 TI - Laboratory and clinical trials of cocamide diethanolamine lotion against head lice. AB - Context. During the late 1990s, insecticide resistance had rendered a number of treatment products ineffective; some companies saw this as an opportunity to develop alternative types of treatment. We investigated the possibility that a surfactant-based lotion containing 10% cocamide diethanolamine (cocamide DEA) was effective to eliminate head louse infestation. Settings and Design. Initial in vitro testing of the lotion formulation versus laboratory reared body/clothing lice, followed by two randomised, controlled, community-based, assessor blinded, clinical studies. Materials and Methods. Preliminary laboratory tests were performed by exposing lice or louse eggs to the product using a method that mimicked the intended use. Clinical Study 1: Children and adults with confirmed head louse infestation were treated by investigators using a single application of aqueous 10% cocamide DEA lotion applied for 60 min followed by shampooing or a single 1% permethrin creme rinse treatment applied to pre-washed hair for 10 min. Clinical Study 2: Compared two treatment regimens using 10% cocamide DEA lotion that was concentrated by hair drying. A single application left on for 8 h/overnight was compared with two applications 7 days apart of 2 h duration, followed by a shampoo wash. Results. The initial laboratory tests showed a pediculicidal effect for a 60 min application but limited ovicidal effect. A longer application time of 8 h or overnight was found capable of killing all eggs but this differed between batches of test material. Clinical Study 1: Both treatments performed badly with only 3/23 (13%) successful treatments using cocamide DEA and 5/25 (23.8%) using permethrin. Clinical Study 2: The single overnight application of cocamide DEA concentrated by hair drying gave 10/56 (17.9%) successes compared with 19/56 (33.9%) for the 2 h application regimen repeated after 1 week. Intention to treat analysis showed no significant difference (p = 0.0523) between the treatments. Over the two studies, there were 18 adverse events possibly or probably associated with treatment, most of which were increased pruritus after treatment. Conclusions. Cocamide DEA 10% lotion, even when concentrated by hair drying, showed limited activity to eliminate head louse infestation. PMID- 26557440 TI - Development and application of molecular biomarkers for characterizing Caribbean Yellow Band Disease in Orbicella faveolata. AB - Molecular stress responses associated with coral diseases represent an under studied area of cnidarian transcriptome investigations. Caribbean Yellow Band Disease (CYBD) is considered a disease of Symbiodinium within the tissues of the coral host Orbicella faveolata. There is a paucity of diagnostic tools to assist in the early detection and characterization of coral diseases. The validity of a diagnostic test is determined by its ability to distinguish host organisms that have the disease from those that do not. The ability to detect and identify disease-affected tissue before visible signs of the disease are evident would then be a useful diagnostic tool for monitoring and managing disease outbreaks. Representational Difference Analysis (RDA) was utilized to isolate differentially expressed genes in O. faveolata exhibiting CYBD. Preliminary screening of RDA products identified a small number of genes of interest (GOI) which included an early growth response factor and ubiquitin ligase from the coral host as well as cytochrome oxidase from the algal symbiont. To further characterize the specificity of response, quantitative real-time PCR (qPCR) was utilized to compare the expression profiles of these GOIs within diseased tissues (visible lesions), tissues that precede visible lesions by 2-4 cm (transition area), and tissues from healthy-looking colonies with no signs of disease. Results show there are distinctive differences in the expression profiles of these three GOIs within each tissue examined. Collectively, this small suite of GOIs can provide a molecular "finger print" which is capable of differentiating between infected and uninfected colonies on reefs where CYBD is known to occur. PMID- 26557441 TI - Rapid loss of phosphorus during early pedogenesis along a glacier retreat choronosequence, Gongga Mountain (SW China). AB - The loss of phosphorus (P) during the early pedogenesis stage is important at the ecosystem level, and it also plays an important role in the global P cycle. The seasonal variation of total P (Pt) and its fractions along a young soil chronosequence (Hailuogou chronosequence) on the eastern slope of Gongga Mountain, SW China, was investigated based on the modified Hedley fractionation technique to understand P loss during the early pedogenesis stage. The results showed that the mineral P (mainly apatite) was the dominant fraction of Pt in the C horizon of the soil, and the seasonal difference in Pt and its fractions was insignificant. In the A horizon, Pt concentrations decreased markedly compared with those in the C horizon, and as the age of the soil increased, the inorganic P (Pi) significantly decreased and the organic P (Po) prominently increased. Seasonally, the P fractions exhibited various distributions in the A horizon. The variation of Pt and its fractions revealed that the P loss was rapid along the 120-year soil chronosequence. The P stocks in soils (0-30 cm) started to decrease at the 52 year site. And the P stock depletion reached almost 17.6% at the 120 year site. The loss of P from the soil of the Hailuogou chronosequence was mainly attributed to weathering, plant uptake, and transport by runoff. About 36% P loss was transported into plant biomass P at the 120 year site. The data obtained indicated that the glacier retreat chronosequence could be used to elucidate the fast rate of P loss during the early pedogenic stage. PMID- 26557443 TI - Preparedness for Ebola Virus Disease. PMID- 26557444 TI - WMA Resolution on Unproven Therapy and the Ebola Virus: Adopted by the 65th WMA General Assembly, Durban, South Africa, October 2014. PMID- 26557445 TI - WMA Resolution on Ebola Viral Disease: Adopted by the 65th WMA General Assembly, Durban, South Africa, October 2014. PMID- 26557442 TI - The herbaceous landlord: integrating the effects of symbiont consortia within a single host. AB - Plants are typically infected by a consortium of internal fungal associates, including endophytes in their leaves, as well as arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) in their roots. It is logical that these organisms will interact with each other and the abiotic environment in addition to their host, but there has been little work to date examining the interactions of multiple symbionts within single plant hosts, or how the relationships among symbionts and their host change across environmental conditions. We examined the grass Agrostis capillaris in the context of a climate manipulation experiment in prairies in the Pacific Northwest, USA. Each plant was tested for presence of foliar endophytes in the genus Epichloe, and we measured percent root length colonized (PRLC) by AMF and DSE. We hypothesized that the symbionts in our system would be in competition for host resources, that the outcome of that competition could be driven by the benefit to the host, and that the host plants would be able to allocate carbon to the symbionts in such a way as to maximize fitness benefit within a particular environmental context. We found a correlation between DSE and AMF PRLC across climatic conditions; we also found a fitness cost to increasing DSE colonization, which was negated by presence of Epichloe endophytes. These results suggest that selective pressure on the host is likely to favor host/symbiont relationships that structure the community of symbionts in the most beneficial way possible for the host, not necessarily favoring the individual symbiont that is most beneficial to the host in isolation. These results highlight the need for a more integrative, systems approach to the study of host/symbiont consortia. PMID- 26557446 TI - The Communication of Information Such as Evacuation Orders at the Time of a Nuclear Power Station Accident: -Recommendations for responses by the national government and electric power utilities to the "Information Disaster". AB - This research was carried out from the perspective that the damage to the people of Fukushima and others from the Fukushima Daiichi Nuclear Power Station (NPS) accident was an "information disaster." It evaluated the critical problems raised by and actual condition analysis on the process of events in the Fukushima Daiichi NPS disaster and responses of the governments and others, notification of the occurrence of the accident and evacuation order by the national and local governments and the evacuation of residents, and guidance for distribution and intake of stable iodine tablets. The research aimed to provide a basis for the implementation of effective distribution and intake of stable iodine tablets and responses to the "information disaster" in the nuclear power disaster. On March 15 at the time that the most radioactive substances were dispersed, even when the average wind speed at the site area was 1.6 m/s, the radioactive substances had reached the outer boundary of Urgent Protective action planning Zone (UPZ, the region with a radius of 30 km) within about five hours. Because of this, every second counted in the provision of information about the accident and the issuance of evacuation orders. This study evaluated the actual condition of information provision by the national government and others from the perspective of this awareness of the importance of time. On the basis of the results of this kind of consideration, we come to the following recommendations: The Nuclear Emergency Response Guidelines and the system for communication of information to medical providers should be revised. The national government should make preparations for the effective advance distribution and intake of stable iodine tablets. PMID- 26557447 TI - Japan Medical Association Junior Doctors Network Report on the WMA Council Session, Tokyo 2014. PMID- 26557448 TI - Japan Medical Association Junior Doctors Network Report on the WMA General Assembly, Durban 2014. PMID- 26557449 TI - Disaster Management at Soma General Hospital in Response to the Great East Japan Earthquake. PMID- 26557450 TI - Don't Drink Unboiled Water in Unfamiliar Places!-Taro Takemi's Success Story. PMID- 26557451 TI - From the Editor's Desk. PMID- 26557453 TI - Historical Changes in Home Care Service and Its Future Challenges. PMID- 26557454 TI - Current Conditions and Issues for Home Care Support Clinics. PMID- 26557455 TI - Regional Collaboration in Home Care Services. PMID- 26557456 TI - Visiting Care by Family Physicians. PMID- 26557457 TI - The Present Situation and the Problem of Visiting Nursing: Team Care Management of Pressure Ulcers in the Elderly. PMID- 26557458 TI - Long-term Care Insurance Act and Home Care. PMID- 26557459 TI - Infection Prevention and Control at Home. PMID- 26557460 TI - Nutritional Management in Home Care: Including Eating Disorder and Dysphagia Assessments. PMID- 26557461 TI - Home Respiratory Management: From COPD to Neurological Diseases. PMID- 26557462 TI - Home Rehabilitation. PMID- 26557463 TI - Death, Dignity, and the Significance of Home Hospice Care. PMID- 26557464 TI - Current Situations and Problems of Home Care for Children. PMID- 26557465 TI - Efforts of Medical Associations to Support Home Medical Care Services: Case of the Nagasaki City Medical Association. PMID- 26557466 TI - Home Medical Care That a Local Medical Association Works On: The Case of Itabashi Medical Association, Tokyo, Japan. PMID- 26557467 TI - Efforts of Medical Associations to Support Home Medical Care Services: The Case of the Shizuoka Medical Association. PMID- 26557468 TI - Efforts of Medical Associations to Support Home Care Services: The Cases of Ichikawa City and Chiba Prefecture Medical Associations. PMID- 26557469 TI - From the Editor's Desk. PMID- 26557470 TI - Groundwater vulnerability to pollution mapping of Ranchi district using GIS. AB - Groundwater pollution due to anthropogenic activities is one of the major environmental problems in urban and industrial areas. The present study demonstrates the integrated approach with GIS and DRASTIC model to derive a groundwater vulnerability to pollution map. The model considers the seven hydrogeological factors [Depth to water table (D), net recharge (R), aquifer media (A), soil media (S), topography or slope (T), impact of vadose zone (I) and hydraulic Conductivity(C)] for generating the groundwater vulnerability to pollution map. The model was applied for assessing the groundwater vulnerability to pollution in Ranchi district, Jharkhand, India. The model was validated by comparing the model output (vulnerability indices) with the observed nitrate concentrations in groundwater in the study area. The reason behind the selection of nitrate is that the major sources of nitrate in groundwater are anthropogenic in nature. Groundwater samples were collected from 30 wells/tube wells distributed in the study area. The samples were analyzed in the laboratory for measuring the nitrate concentrations in groundwater. A sensitivity analysis of the integrated model was performed to evaluate the influence of single parameters on groundwater vulnerability index. New weights were computed for each input parameters to understand the influence of individual hydrogeological factors in vulnerability indices in the study area. Aquifer vulnerability maps generated in this study can be used for environmental planning and groundwater management. PMID- 26557471 TI - Barriers and facilitators to recruitment to a culturally-based dietary intervention among urban Hispanic breast cancer survivors. AB - PURPOSE: The purpose of this study was to understand factors related to recruitment to behavioral intervention trials among Spanish-speaking urban Hispanic breast cancer (BC) survivors. METHODS: Potentially eligible Hispanic BC survivors were recruited from the Columbia University Breast Oncology Clinic, signed informed consent, and completed a screening interview on demographics, medical history, acculturation (Short Acculturation Scale for Hispanics), quality of life (QOL), and perceived benefits/risks of research participation. Trial eligibility criteria included stage 0-III BC, completion of adjuvant treatment, Hispanic, fluency in Spanish, willing to be randomized to active arm (9-session in-person culturally-based !Cocinar para su salud! dietary modification program) or control arm (written materials). We compared characteristics between eligible women who did and did not enroll in the trial. RESULTS: 102 women completed the screening interview and were eligible to participate. Overall mean age was 57.3 +/- 9.5 years, mean time since diagnosis was 3.4 +/- 2.1 years, 71% reported annual household income <$15,000 and mean acculturation index score was 1.6 +/- 0.6 (scale 1-5, low-high). Of the 102 women, 70 enrolled and 32 declined participation. Reasons stated for non-participation included lack of interest in dietary change, illness, and work constraints. Compared to women who enrolled, women who did not enroll were less likely to be employed (P=0.03) and more likely to only read/speak Spanish (P=0.02). Compared to women who enrolled, non enrollers were more likely to state that research is costly to participants (P=0.03). CONCLUSION: Lower participation was associated with unemployment, monolingualism, and the perception that research is costly to participants. Future behavioral intervention trials among minority BC survivors need to account for these and other factors that may be related to trial participation. PMID- 26557472 TI - Broccoli-Derived Sulforaphane and Chemoprevention of Prostate Cancer: From Bench to Bedside. AB - Sulforaphane (SFN) is a metabolic by product of cruciferous vegetables and is the biologically active phytochemical found in high concentrations in broccoli. It has been studied extensively for its anticancer efficacy and the underlying mechanisms using cell culture and preclinical models. The immediate precursor of SFN is glucoraphanin, a glucosinolate which requires metabolic conversion to SFN. SFN and other notable isothiocyanates, including phenethyl isothiocyanate and benzyl isothiocyanate found in various cruciferous vegetables, have also been implicated to have a chemopreventive role for breast, colon and prostate cancer. In-vitro and in-vivo anti-cancer activity of this class of compounds summarizing the past two decades of basic science research has previously been reviewed by us and others. The present review aims to focus specifically on SFN and its chemopreventive and antineoplastic activity against prostate cancer. Particular emphasis in this communication is placed on the current status of clinical research and prospects for future clinical trials with the overall objective to better understand the clinical utility of this promising chemopreventive nutraceutical in the context of mechanisms of prostate carcinogenesis. PMID- 26557473 TI - The Association of Alcohol and Drug Use with Persistence of Violent Offending in Young Adulthood. AB - PURPOSE: This study expanded upon an earlier study, which examined the associations between heavy drinking and persistence of serious violent offending through emerging adulthood (approximate age 25), by examining associations between alcohol, marijuana, and other drug use and disorders and persistence of serious violent offending through young adulthood (approximate age 36). METHODS: We used official records and self-reported longitudinal data from Black and White men from early adolescence through young adulthood (n = 391). Men were divided into four violence groups: non-violent, desisters, persisters, and very late onsetters. Multinomial logistic regression analyses controlling for race and incarceration were used to compare these groups in terms of substance use in young adulthood and changes in use from emerging to young adulthood. RESULTS: Most previous serious violent offenders did not re-offend in young adulthood. Whereas alcohol use did not differ across groups, persisters and desisters, compared to non-violent men, were more likely to use hard drugs, deal drugs, have a lifetime substance use disorder diagnosis and show larger decreases in alcohol and marijuana frequency from emerging to young adulthood. None of these measures differed between persisters and desisters except that persisters reported larger decreases in alcohol and marijuana use frequency. CONCLUSIONS: The findings demonstrated reductions in serious violent offending during young adulthood and suggested that after adolescence, illicit drug use, compared to alcohol use, may play a more important role in initiation and maintenance of serious violent offending. Future research that examines the interrelations of drug use, drug culture, and violence is warranted. PMID- 26557474 TI - An efficient protocol for deriving liver stem cells from neonatal mice: validating its differentiation potential. AB - The success of liver regeneration depends on the availability of suitable cell types and their potential to differentiate into functional hepatocytes. To identify the stem cells which have the ability to differentiate into hepatocytes, we used neonatal liver as source. However, the current protocol for isolating stem cells from liver involves enzymes like collagenase, hyaluronidase exposed for longer duration which limits the success. This results in the keen interest to develop an easy single step enzyme digestion protocol for isolating stem cells from liver for tissue engineering approaches. Thus, the unlimited availability of cell type favors setting up the functional recovery of the damaged liver, ensuring ahead success towards treating liver diseases. We attempted to isolate liver stem derived cells (LDSCs) from mouse neonatal liver using single step minimal exposure to enzyme followed by in vitro culturing. The cells isolated were characterized for stem cell markers and subjected to lineage differentiation. Further, LDSCs were induced to hepatocyte differentiation and validated with hepatocyte markers. Finally, we developed a reproducible, efficient protocol for isolation of LDSCs with functional hepatocytes differentiation potential, which further can be used as in vitro model system for assessing drug toxicity assays in various preclinical trials. PMID- 26557475 TI - Factors Associated with Sexual Orientation and Gender Disparities in Chronic Pain Among U.S. Adolescents and Young Adults. AB - OBJECTIVE: This research investigated factors associated with sexual orientation disparities in chronic pain frequency among youth. METHOD: Data were analyzed from 4534 female and 3785 male youth from Waves I-IV (1995-2009) of the U.S. National Longitudinal Study of Adolescent to Adult Health. Gender-stratified weighted logistic regression models controlled for sociodemographic characteristics and included sexual orientation (primary predictor) and frequency of three types of chronic pain (outcomes). Models with sexual orientation only were compared to models with factors hypothesized to increase or decrease risk of pain. Significant odds ratios (OR) for chronic pain frequency (daily/weekly vs. rarely) with confidence intervals (CI) and associated factors are reported. RESULTS: Compared to same-gender heterosexual females, mostly heterosexuals were more likely to report headaches (OR=1.40, CI=1.09, 1.79) and mostly heterosexuals and bisexuals were more likely to report muscle/joint pain (mostly heterosexual OR=1.69, CI=1.29, 2.20; bisexual OR=1.87, CI=1.03, 3.38). Compared to same-gender heterosexual males, gay males were more likely to report headaches (OR=2.00, CI=1.06, 3.82), but less likely to report muscle/joint pain (OR=0.28, CI=0.11, 0.74). Significant disparities were attenuated by up to 16% when associated factors were added to the model. CONCLUSION: Sexual orientation disparities in chronic pain were partially explained by associated factors, but more research is needed to develop intervention and prevention strategies. PMID- 26557477 TI - Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension? AB - Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD >= 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of increased endothelin-1 activity and impaired nitric oxide-dependent vasodilation. Unfortunately, so far, there is no evidence supporting the use of specific PAH therapies in patients with PH related to left heart disease. In conclusion, the presence of PH in patients with conditions other than PAH contributes to the severity of the disease, affecting the outcome and quality of life. The disappointing results regarding the effectiveness of specific PAH therapies in patients with chronic lung diseases and LHD underline the need for seeking new underlying mechanisms and thus novel therapies targeting PH due to left heart disease and/or lung diseases. PMID- 26557476 TI - Deep sternal wound infection after cardiac surgery: Evidences and controversies. AB - Despite many advances in prevention and perioperative care, deep sternal wound infection (DSWI) remains a pressing concern in cardiac surgery, with a still relevant incidence and with a considerable impact on in-hospital mortality and also on mid- and long-term survival. The permanent high impact of this complication is partially related to the increasing proportion of patients at high-risk for infection, as well as to the many patient and surgical risk factors involved in the pathogenesis of DSWI. The prophylactic antibiotic therapy is one of the most important tools in the prevention of DSWI. However, the choice of antibiotic, the dose, the duration, the adequate levels in serum and tissue, and the timing of antimicrobial prophylaxis are still controversial. The treatment of DSWI ranges from surgical revision with primary closure to surgical revision with open dressings or closed irrigation, from reconstruction with soft tissue flaps to negative pressure wound therapy (NPWT). However, to date, there have been no accepted recommendations regarding the best management of DSWI. Emerging evidence in the literature has validated the efficacy and safety of NPWT either as a single-line therapy, or as a "bridge" prior to final surgical closure. In conclusion, the careful control of patient and surgical risk factors - when possible, the proper antimicrobial prophylaxis, and the choice of validated techniques of treatment could contribute to keep DSWIs at a minimal rate. PMID- 26557478 TI - Recruitment maneuvers in acute respiratory distress syndrome: The safe way is the best way. AB - Acute respiratory distress syndrome (ARDS) represents a serious problem in critically ill patients and is associated with in-hospital mortality rates of 33% 52%. Recruitment maneuvers (RMs) are a simple, low-cost, feasible intervention that can be performed at the bedside in patients with ARDS. RMs are characterized by the application of airway pressure to increase transpulmonary pressure transiently. Once non-aerated lung units are reopened, improvements are observed in respiratory system mechanics, alveolar reaeration on computed tomography, and improvements in gas exchange (functional recruitment). However, the reopening process could lead to vascular compression, which can be associated with overinflation, and gas exchange may not improve as expected (anatomical recruitment). The purpose of this review was to discuss the effects of different RM strategies - sustained inflation, intermittent sighs, and stepwise increases of positive end-expiratory pressure (PEEP) and/or airway inspiratory pressure - on the following parameters: hemodynamics, oxygenation, barotrauma episodes, and lung recruitability through physiological variables and imaging techniques. RMs and PEEP titration are interdependent events for the success of ventilatory management. PEEP should be adjusted on the basis of respiratory system mechanics and oxygenation. Recent systematic reviews and meta-analyses suggest that RMs are associated with lower mortality in patients with ARDS. However, the optimal RM method (i.e., that providing the best balance of benefit and harm) and the effects of RMs on clinical outcome are still under discussion, and further evidence is needed. PMID- 26557479 TI - In vivo analysis of intestinal permeability following hemorrhagic shock. AB - AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation. RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 +/- 0.19 vs 0.86 +/- 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 +/- 0.18 vs 0.97 +/- 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 +/- 6.52 vs 3.38 +/- 1.11 fluorescent intensity units (* 10(5), P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure. PMID- 26557480 TI - Therapeutic temperature modulation is associated with pulmonary complications in patients with severe traumatic brain injury. AB - AIM: To examine complications associated with the use of therapeutic temperature modulation (mild hypothermia and normothermia) in patients with severe traumatic brain injury (TBI). METHODS: One hundred and fourteen charts were reviewed. Inclusion criteria were: severe TBI with Glasgow Coma Scale (GCS) < 9, intensive care unit (ICU) stay > 24 h and non-penetrating TBI. Patients were divided into two cohorts: the treatment group received therapeutic temperature modulation (TTM) with continuous surface cooling and indwelling bladder temperature probes. The control group received standard treatment with intermittent acetaminophen for fever. Information regarding complications during the time in the ICU was collected as follows: Pneumonia was identified using a combination of clinical and laboratory data. Pulmonary embolism, pneumothorax and deep venous thrombosis were identified based on imaging results. Cardiac arrhythmias and renal failure were extracted from the clinical documentation. acute respiratory distress syndrome and acute lung injury were determined based on chest imaging and arterial blood gas results. A logistic regression was conducted to predict hospital mortality and a multiple regression was used to assess number and type of clinical complications. RESULTS: One hundred and fourteen patients were included in the analysis (mean age = 41.4, SD = 19.1, 93 males), admitted to the Jackson Memorial Hospital Neuroscience ICU and Ryder Trauma Center (mean GCS = 4.67, range 3-9), were identified and included in the analysis. Method of injury included motor vehicle accident (n = 29), motor cycle crash (n = 220), blunt head trauma (n = 212), fall (n = 229), pedestrian hit by car (n = 216), and gunshot wound to the head (n = 27). Ethnicity was primarily Caucasian (n = 260), as well as Hispanic (n = 227) and African American (n = 223); four patients had unknown ethnicity. Patients received either TTM (43) or standard therapy (71). Within the TTM group eight patients were treated with normothermia after TBI and 35 patients were treated with hypothermia. A logistic regression predicting in hospital mortality with age, GCS, and TM demonstrated that GCS (Beta = 0.572, P < 0.01) and age (Beta = -0.029) but not temperature modulation (Beta = 0.797, ns) were significant predictors of in-hospital mortality [chi(2) (3) = 22.27, P < 0.01] A multiple regression predicting number of complications demonstrated that receiving TTM was the main contributor and was associated with a higher number of pulmonary complications (t = -3.425, P = 0.001). CONCLUSION: Exposure to TTM is associated with an increase in pulmonary complications. These findings support more attention to these complications in studies of TTM in TBI patients. PMID- 26557481 TI - What is new in critical illness and injury science? Patient safety amidst chaos: Are we on the same team during emergency and critical care interventions? PMID- 26557482 TI - Regional anesthesia for management of acute pain in the intensive care unit. AB - Pain is a major problem for Intensive Care Unit (ICU) patients. Despite numerous improvements it is estimated that as many as 70% of the patients experience moderate-to-severe postoperative pain during their stay in the ICU. Effective pain management means not only decreasing pain intensity, but also reducing the opioids' side effects. Minimizing nausea, vomiting, urinary retention, and sedation may indeed facilitate patient recovery and it is likely to shorten the ICU and hospital stay. Adequate postoperative and post-trauma pain management is also crucial for the achievement of effective rehabilitation. Furthermore, recent studies suggest that effective acute pain management may be helpful in reducing the development of chronic pain. When used appropriately, and in combination with other treatment modalities, regional analgesia techniques (neuraxial and peripheral nerve blocks) have the potential to reduce or eliminate the physiological stress response to surgery and trauma, decreasing the possibility of surgical complications and improving the outcomes. Also they may reduce the total amount of opioid analgesics necessary to achieve adequate pain control and the development of potentially dangerous side effects. PMID- 26557483 TI - Prognosis of critical surgical patients depending on the duration of stay in the ICU. AB - OBJECTIVE: To analyze the epidemiological and prognostic differences between critical surgical patients admitted to intensive care unit (ICU) according to length of stay in the ICU. MATERIALS AND METHODS: Retrospective observational study on patients with surgical pathology admitted to ICU of a tertiary hospital, during 7 years, with a stay >= 5 days. The variables analyzed were age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II), duration of stay, hospital and ICU mortality, original service, reason for admission, geographical place of residence, and the use of invasive techniques such as mechanical ventilation (MV), tracheotomy, and techniques of continuous renal replacement (CRR). Two groups were defined; one with intermediate stay, the one that exceeds the average of our population (> 5 days) and another with long stay patients (> 14 days). Readmissions were excluded. Firstly, the analysis of differential characteristics of patients was performed, this was according to the duration of their stay using either a contrast equal averages when the variable contrast between the two groups was quantitative or the Chi-square test when the variable analyzed was qualitative. For both tests, the existence of significant differences between groups was considered when the significance level was less than 5%. And, secondly, a model forecast ICU survival of these patients, regardless of length of stay in ICU, using a binary logistic regression analysis was performed. RESULTS: Among the 540 patients analyzed, no significant differences were observed, depending on the length of stay in the ICU, except the need for invasive techniques such as MV or tracheotomy in those of longer stay (P = 0.000). However, ICU mortality was significantly higher for patients with intermediate stay (30 vs 17: 5%; P = 0.000), without observing differences in hospital mortality. ICU survival was influenced by age, APACHE II levels, admission to the ICU in a coma state, and the application of the three invasive techniques discussed. CONCLUSION: Surgical patients who survive in the ICU, regardless of the length of their stay in it, have the same odds of hospital survival. Found as predictors of mortality in ICU APACHE II, age, admission in a coma state, and application of invasive techniques. PMID- 26557484 TI - Can enteral antibiotics be used to treat pneumonia in the surgical intensive care unit? A clinical outcomes and cost comparison. AB - BACKGROUND: Controlling healthcare costs without compromising patient care is a focus given recent healthcare changes in the United States. The purpose of this study was to assess clinical improvement in surgical intensive care unit (SICU) patients initiated on or transitioned to enteral antibiotics compared to those who solely receive intravenous (IV) antibiotic therapy for treatment of bacterial pneumonia. MATERIALS AND METHODS: This retrospective cohort study included patients with a positive quantitative respiratory culture being treated for bacterial pneumonia in a SICU from 1/1/09 to 3/31/11. Two distinct patient groups were identified: Those treated with IV antibiotics exclusively (IV) and those either initiated on or transitioned to enteral antibiotics within 4 days of antibiotic initiation (PO). The primary endpoint of clinical improvement was assessed on day of antibiotic discontinuation. RESULTS: A total of 647 patients were evaluated; 124 met inclusion criteria (30 patients PO group and 94 IV group). There was no difference in clinical improvement (86.7 PO vs 72.3% IV, P = 0.14) or recurrence (10 PO vs. 12.8% IV, P > 0.99) between groups. Secondary outcomes of duration of mechanical ventilation, ICU and hospital length of stay, and all-cause mortality were also similar. Antibiotic and infection-related costs were significantly decreased in the PO group ($1,042 vs $697, P = 0.04; $20,776 vs $17,381, P = 0.012, respectively). CONCLUSIONS: SICU patients initiated on or transitioned to PO antibiotics for pneumonia had similar clinical outcomes, but significantly less infection-related and antibiotic costs compared to those receiving IV therapy. Further, prospective studies are warranted. PMID- 26557485 TI - Direct (presenting primarily to trauma center) versus indirect (referred or transferred) admission of patients to the Trauma Centre of King George Medical University: One-year prospective pilot study. AB - BACKGROUND: India does not have a trauma registry. There is lack of base line demographic data of trauma victims that present directly to the trauma center and those that are transferred to the trauma center. AIM: To compare the clinical and demographic profile of directly admitted (presenting primarily to the trauma center) and referred (transferred to trauma center) patients at the trauma centre of King George Medical University. MATERIALS AND METHODS: The demographic and clinical profiles of patients admitted on thirty-three consecutive Mondays were collected and compared. In addition, the demographic data of patients admitted on Mondays and eight randomly selected Wednesdays and Saturdays were analyzed to ascertain the representativeness of the studied sample. RESULTS: Of the 572 patients in the study, 327 were referred and 245 were directly admitted. There was 27% mortality in the referred group and 22% mortality in the directly admitted group, the difference been statistically insignificant (P value 0.20). Patients referred from peripheral hospitals were more severely injured with a lower GCS and a higher TRISS, and had a higher proportion of multi system major trauma and severe head injury. CONCLUSION: Referred admitted (transferred) patients at the KGMU trauma center are more seriously injured than the patients presenting directly. Yet there is no statistically significant difference in the overall mortality. A future study focusing on certain sub-categories of patients such as those demonstrating subdural hematoma, GCS less than 9 or ISS more than 15 may yield interesting data. PMID- 26557486 TI - Complications of needle thoracostomy: A comprehensive clinical review. AB - Needle thoracostomy (NT) is a valuable adjunct in the management of tension pneumothorax (tPTX), a life-threatening condition encountered mainly in trauma and critical care environments. Most commonly, needle thoracostomies are used in the prehospital setting and during acute trauma resuscitation to temporize the affected individuals prior to the placement of definitive tube thoracostomy (TT). Because it is both an invasive and emergent maneuver, NT can be associated with a number of potential complications, some of which may be life-threatening. Due to relatively common use of this procedure, it is important that healthcare providers are familiar, and ready to deal with, potential complications of NT. PMID- 26557487 TI - Central line complications. AB - Central venous access is a common procedure performed in many clinical settings for a variety of indications. Central lines are not without risk, and there are a multitude of complications that are associated with their placement. Complications can present in an immediate or delayed fashion and vary based on type of central venous access. Significant morbidity and mortality can result from complications related to central venous access. These complications can cause a significant healthcare burden in cost, hospital days, and patient quality of life. Advances in imaging, access technique, and medical devices have reduced and altered the types of complications encountered in clinical practice; but most complications still center around vascular injury, infection, and misplacement. Recognition and management of central line complications is important when caring for patients with vascular access, but prevention is the ultimate goal. This article discusses common and rare complications associated with central venous access, as well as techniques to recognize, manage, and prevent complications. PMID- 26557489 TI - Complications of bronchoscopy: A concise synopsis. AB - Flexible and rigid bronchoscopes are used in diagnosis, therapeutics, and palliation. While their use is widespread, effective, and generally safe; there are numerous potential complications that can occur. Mechanical complications of bronchoscopy are primarily related to airway manipulations or bleeding. Systemic complications arise from the procedure itself, medication administration (primarily sedation), or patient comorbidities. Attributable mortality rates remain low at < 0.1% for fiberoptic and rigid bronchoscopy. Here we review the complications (classified as mechanical or systemic) of both rigid and flexible bronchoscopy in hope of making practitioners who are operators of these tools, and those who consult others for interventions, aware of potential problems, and pitfalls in order to enhance patient safety and comfort. PMID- 26557488 TI - An overview of complications associated with open and percutaneous tracheostomy procedures. AB - Tracheostomy, whether open or percutaneous, is a commonly performed procedure and is intended to provide long-term surgical airway for patients who are dependent on mechanical ventilatory support or require (for various reasons) an alternative airway conduit. Due to its invasive and physiologically critical nature, tracheostomy placement can be associated with significant morbidity and even mortality. This article provides a comprehensive overview of commonly encountered complications that may occur during and after the tracheal airway placement, including both short- and long-term postoperative morbidity. PMID- 26557490 TI - Laparoscopy in trauma: An overview of complications and related topics. AB - The introduction of laparoscopy has provided trauma surgeons with a valuable diagnostic and, at times, therapeutic option. The minimally invasive nature of laparoscopic surgery, combined with potentially quicker postoperative recovery, simplified wound care, as well as a growing number of viable intraoperative therapeutic modalities, presents an attractive alternative for many traumatologists when managing hemodynamically stable patients with selected penetrating and blunt traumatic abdominal injuries. At the same time, laparoscopy has its own unique complication profile. This article provides an overview of potential complications associated with diagnostic and therapeutic laparoscopy in trauma, focusing on practical aspects of identification and management of laparoscopy-related adverse events. PMID- 26557493 TI - The use of cryotherapy via bronchoscopy for removal of obstructing tracheobronchial thrombi. PMID- 26557492 TI - Colosplenic contained perforation secondary to colonic lymphoma. AB - We present the case of patient with colosplenic perforation from a colonic lymphoma. He initially was diagnosed with a splenic abscess subsequently developed a contained colonic perforation, underwent surgical treatment and intraoperatively was diagnosed with lymphoma. This is a rare entity in a non immunocompromised host and has been scarcely reported. PMID- 26557491 TI - Complications of pericardiocentesis: A clinical synopsis. AB - Pericardiocentesis (PC) is both a diagnostic and a potentially life-saving therapeutic procedure. Currently echocardiography-guided pericardiocentesis is considered the standard clinical practice in the treatment of large pericardial effusions and cardiac tamponade. Although considered relatively safe, this invasive procedure may be associated with certain risks and potentially serious complications. This review provides a summary of pericardiocentesis and a focused overview of the potential complications of this procedure. PMID- 26557494 TI - Renal leak; mechanism of hypercalciuria in short-term immobilization. PMID- 26557495 TI - Mean platelet volume a key or obstacle in clinical affairs. PMID- 26557496 TI - Hypercapnia during endoscopic saphenectomy complicating CABG. PMID- 26557497 TI - Catheter-related infections. PMID- 26557498 TI - Extensive descending necrotizing mediastinitis can be managed conservatively. PMID- 26557499 TI - A letter in response to impact of acetazolamide use in severe exacerbation of chronic obstructive pulmonary disease requiring invasive mechanical ventilation. PMID- 26557500 TI - Ovarian Cancer Molecular Stratification and Tumor Heterogeneity: A Necessity and a Challenge. PMID- 26557501 TI - The Impact of Neutrons in Clinical Proton Therapy. AB - In proton therapy, high-energy proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long-term health of cancer patients. Due to the high biological effectiveness of neutrons with regard to cancer induction, small neutron doses can be important. Published comparisons of neutron dose measurements and the corresponding estimates of cancer risk between different treatment modalities differ over orders of magnitude. In this report, the controversy about the impact of the neutron dose in proton therapy is critically discussed and viewed in the light of new epidemiological studies. In summary, the impact of neutron dose on cancer risk can be determined correctly only if the dose distributions are carefully measured or computed. It is important to include not only the neutron component into comparisons but also the complete deposition of energy as precisely as possible. Cancer risk comparisons between different radiation qualities, treatment machines, and techniques have to be performed under similar conditions. It seems that in the past, the uncertainty in the models which lead from dose to risk were overestimated when compared with erroneous dose comparisons. Current risk models used with carefully obtained dose distributions predict a second cancer risk reduction for active protons vs. photons and a more or less constant risk of passive protons vs. photons. Those findings are in general agreement with newly obtained epidemiologically results. PMID- 26557502 TI - Exome Sequencing of an Adult Pituitary Atypical Teratoid Rhabdoid Tumor. AB - Atypical teratoid rhabdoid tumors (AT/RTs) are rare pediatric brain tumors characterized by bialleic loss of the SMARCB1 tumor suppressor gene. In contrast to pediatric AT/RT that has a simple genome, very little is known about the adult AT/RT genomic landscape. Using a combination of whole-exome sequencing and high resolution SNP array in a single adult pituitary AT/RT, we identified a total of 47 non-synonymous mutations, of which 20 were predicted to cause non-conservative amino acid substitutions, in addition to a subclone of cells with trisomy 8. We suggest that adult AT/RT may not be markedly dissimilar to other adult brain tumors where mutations in a range of genes, reflecting the functional specialization of different brain regions, but including SMARCB1 inactivation, may be required for its pathogenesis. PMID- 26557504 TI - Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones. AB - INTRODUCTION: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. METHODS: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by hematoxylin-eosin, Masson's Trichrome and Ki-67 staining at 1, 4, 10, and 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti alphaSMA and anti-CD45, respectively. RESULTS: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as 1 week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy. CONCLUSION: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy. PMID- 26557503 TI - DIPG in Children - What Can We Learn from the Past? AB - Brainstem tumors represent 10-15% of pediatric central nervous system tumors and diffuse intrinsic pontine glioma (DIPG) is the most common brainstem tumor of childhood. DIPG is almost uniformly fatal and is the leading cause of brain tumor related death in children. To date, radiation therapy (RT) is the only form of treatment that offers a transient benefit in DIPG. Chemotherapeutic strategies including multi-agent neoadjuvant chemotherapy, concurrent chemotherapy with RT, and adjuvant chemotherapy have not provided any survival advantage. To overcome the restrictive ability of the intact blood-brain barrier (BBB) in DIPG, several alternative drug delivery strategies have been proposed but have met with minimal success. Targeted therapies either alone or in combination with RT have also not improved survival. Five decades of unsuccessful therapies coupled with recent advances in the genetics and biology of DIPG have taught us several important lessons (1). DIPG is a heterogeneous group of tumors that are biologically distinct from other pediatric and adult high grade gliomas (HGG). Adapting chemotherapy and targeted therapies that are used in pediatric or adult HGG for the treatment of DIPG should be abandoned (2). Biopsy of DIPG is relatively safe and informative and should be considered in the context of multicenter clinical trials (3). DIPG probably represents a whole brain disease so regular neuraxis imaging is important at diagnosis and during therapy (4). BBB permeability is of major concern in DIPG and overcoming this barrier may ensure that drugs reach the tumor (5). Recent development of DIPG tumor models should help us accurately identify and validate therapeutic targets and small molecule inhibitors in the treatment of this deadly tumor. PMID- 26557506 TI - Pelvic Floor Support Defect in Apical Anterior Vaginal Prolapse with Cervical Hypertrophy. Review with Case Report in a 20-year-old Cadaver. AB - Apical anterior vaginal wall prolapse (AVWP) with central defect is uncommon in young non hysterectomized patients causing considerable mortality after the fourth decade of life. Its high propensity to recurrence poses the greatest challenge to pelvic reconstructive surgeons. Approximately 40% of women with prolapse have hypertrophic cervical elongation and the extent of elongation increases with greater degrees of prolapse. Women with prolapse either have inherent hypertrophic elongation of the cervix which predisposes them to prolapse or the downward traction in prolapse leads to cervical elongation. The Pelvic Organ Prolapse Quantification (POP-Q) examination includes measurement of the location of the posterior fornix (point D) with the assumption that this measurement is associated with cervical elongation. Multifocal site involvement with apical and perineal descent primarily afflicts elderly, postmenopausal women after the fourth decade while cervical hypertrophic elongation with prolapse is observed in younger women less than 40 years of age. A review of the anatomical implication of the association of cervical hypertrophy in prolapse is carried out in this article. We observed a combination of distension type anterior vaginal prolapse with apical descent and cervical hypertrophy in a 20-year-old cadaver during routine dissection for undergraduate medical students at Sikkim Manipal Institute of Medical Sciences in 2013. Distension type anterior vaginal prolapse with central defect is rarer as most reported cases are of the displacement type, paravaginal defect. Hypertrophic cervical elongation is either the cause or consequence of prolapse and its identification before reconstructive surgery is paramount as uterine suspension in the face of cervical elongation is contraindicated. Inappropriate identification of all support defects and breaking of tissues is the primary cause of failure of laparoscopic pelvic reconstructive surgery. PMID- 26557505 TI - Study of Third Coronary Artery in Adult Human Cadaveric Hearts. AB - INTRODUCTION: Third coronary artery (TCA) is a direct branch arising from the anterior aortic sinus (right aortic sinus) which supplies right ventricular outflow tract. It is found frequently and may be an important source for collateral coronary blood flow through a vascular anastomotic bridge (circle of Vieussens) between the right and left coronary systems. AIM: To evaluate the gross anatomy of third coronary artery in terms of their number, origin, extent and distribution. MATERIALS AND METHODS: After an ethical approval, 150 formalin fixed adult human cadaveric hearts were collected from Department of Anatomy, BVDU Medical College and Hospital, Sangli and Pune over the period of six years. The careful dissection was carried out to note details about third coronary artery and data was analysed using SPSS computer software. RESULTS: The TCA was present in 32% of the heart specimens. In 42 hearts (28%) single TCA and in 6 hearts (4%) double TCA were noted. It was found to be variably distributed to conus arteriosus, anterior wall of the right ventricle, interventricular septum and the apex of the heart. TCA was larger than right coronary artery in 8 hearts and later ended at inferior border of heart. Myocardial bridge was noted over large third coronary artery in one specimen. CONCLUSION: TCA is present frequently. It anastomoses with branches of left anterior descending artery (LADA) and contributes to apical and septal perfusion. Hence role of TCA should always be considered during diagnostic and therapeutic interventions. PMID- 26557507 TI - Unusual Course of Splenic Artery: A Case Report. AB - Splenic artery is the largest branch from the celiac trunk. It is remarkably tortuous in its course before it enters the hilum of the spleen. During routine dissection of abdomen for undergraduate students in a 60-year-old male cadaver, we observed an unusual course and tortuosity in the splenic artery. Knowledge of such unusual tortuous splenic artery is important in partial or total splenectomy, splenic aneurysum, splenic embolisation and surgeries related to pancreas, stomach. PMID- 26557508 TI - Is Xanthine Oxidase, a Marker in Pre-eclampsia? A Case-Control Study. AB - INTRODUCTION: Pre-eclampsia is an obstetrics problem that affects multiple systemic functions and leads to the increased maternal and fetal morbidity and mortality. The objective of the study was to evaluate the plasma levels of Xanthine oxidase (XO) activity, uric acid and Nitric oxide (NO) levels in women with pre-eclampsia and normal pregnancy during antenatal and postpartum period. MATERIALS AND METHODS: A case control study was conducted in women with normal pregnancy (n=50) and pre-eclampsia (n=50) before and after delivery. XO activity, uric acid and NO levels were determined from samples at 30-39 weeks of gestation. The current study was conducted in association with Obstetrics and Gynecology Department of R.L. Jalappa Hospital and Research Center. The blood samples were analysed for assay of XO, uric acid and NO. The results were analysed by using SPSS software version 2013. P-value < 0.05 was considered as statistically significant. RESULTS: The plasma XO activity was elevated (p<0.001) in the pre eclampsia compared to normotensive pregnant women before delivery and decreased after delivery (p<0.001) significantly. Uric acid level showed a significant increase in pre-eclampsia when compared to the control before delivery (p<0.001) however values were non-significant after delivery. CONCLUSION: Placenta plays a key role in the pathophysiology of pre-eclampsia. Placenta removal leads to decrease trend of xanthine oxidase activity, uric acid and elevation of Nitric oxide as reversible changes in pre-eclampsia patients within 48 hours after delivery. PMID- 26557509 TI - Evaluation of CareSens POCT Devices for Glucose Testing in the Routine Hospital Setting. AB - INTRODUCTION: Glucose meters are used routinely in hospital wards to manage blood glucose levels in patients requiring frequent monitoring of blood glucose. OBJECTIVE: Our institution has 50 POC instruments utilized by diverse population of all ages and medical conditions. The primary objective of our study was to investigate whether all these CareSens glucose meters (I-sense Inc, Seoul, South Korea) results in hospitalized patients during routine clinical care jointly satisfy the specified quality specifications, as defined by Clinical and Laboratory Standards Institute (CLSI) guideline POCT12-A3. MATERIALS AND METHODS: The records of hospitalized patients who underwent simultaneous measures of glucose levels with both glucose meters and a central laboratory analyser between January and June 2013 were retrospectively analysed. We also performed a prospective evaluation of the accuracy of the CareSens glucose Strip. RESULTS: Glucose concentrations measured in 840 patients ranged from 1.66 to 31.72 mmol/L The Bland-Altman difference plot between the auto analyser and all the 50 CareSens glucosemeters revealed a mean bias of -2.2%, with analytical biases for the two methods varying from -31.1% to 26.8%. Eighty four percent of the glucose meter's glucose values were within +/- 12.5% for values 5.54 mmol/L of the comparative laboratory glucose values and 93% of the results were within 20% of the reference for glucose >4.2 mmol/L and 65% of the results were within 0.8 mmol/L for glucose <4.2 mmol/L. CONCLUSION: CareSens glucose meter readings in hospital settings, especially in hypoglycaemic patients, should be confirmed by central laboratory analysers whenever possible. PMID- 26557510 TI - Heart-Type Fatty Acid Binding Protein: A Better Cardiac Biomarker than CK-MB and Myoglobin in the Early Diagnosis of Acute Myocardial Infarction. AB - BACKGROUND: Early diagnosis and therapeutic intervention can improve the outcome of acute myocardial infarction (AMI). However, there are no satisfactory cardiac biomarkers for the diagnosis of AMI within 6 hours of onset of symptoms. Among novel biochemical markers of AMI, heart-type fatty acid binding protein (H-FABP) is of particular interest. AIM: To compare the diagnostic value of H-FABP with that of CK-MB and myoglobin in suspected AMI patients within first 6 hours after the onset of symptoms. SETTINGS AND DESIGN: The study includes 40 AMI cases and 40 non-cardiac chest pain otherwise healthy controls. The cases and controls were further divided into 2 groups depending on the time since chest pain as those subjects within 3 hours and those between 3-6 hours of onset of chest pain. MATERIALS AND METHODS: In all the cases and controls, serum H-FABP, CK-MB and myoglobin concentrations were measured by Immunoturbidimetric method, immuno inhibition method and Chemiluminescence immunoassay respectively. STATISTICAL ANALYSIS: Data is presented as mean +/- SD values. Differences between means of two groups were assessed by Student t-test. Sensitivity, Specificity, Positive predictive value, Negative predictive values were calculated and ROC curve analysis was done to assess the diagnostic validity of each study parameter. RESULTS: The sensitivity, specificity, PPV, NPV of H-FABP were greater than CK-MB and myoglobin and ROC curve analysis demonstrated highest area under curve for H FABP followed by myoglobin and CK-MB in patients with suspected AMI both within 3 hours and 3-6 hours after the onset of chest pain. CONCLUSION: The diagnostic efficiency of H-FABP is greater than CK-MB and myoglobin for the early diagnosis of AMI within first 6 hours of chest pain. H-FABP can be used as an additional diagnostic tool for the early diagnosis of AMI. PMID- 26557511 TI - Laboratory Profiles of Patients on Hemodialysis - A Retrospective One Year Study in a Rural Tertiary Care Hospital. AB - INTRODUCTION: The global prevalence of chronic kidney disease (CKD) is estimated to be 8-16%. Studies have shown that the increased mortality in patients with CKD is due to anemia that leads to cardiovascular disease (CVD), also known as "Cardio renal anemia syndrome". The present study was undertaken to look into the laboratory profiles of end stage renal disease (ESRD) patients. AIM: To study the laboratory profiles of End stage renal disease (ESRD) patients coming for hemodialysis. MATERIALS AND METHODS: The study was a retrospective, cross- sectional study done by collecting data from the medical case records of all patients during a period of one year from January 1(st) 2014 to December 31(st) 2014. Records of a total of 140 patients who underwent hemodialysis during this period were taken. The laboratory profiles that was recorded included haemoglobin, serum sodium, potassium, chloride, fasting glucose, calcium and phosphorus. RESULTS: The mean age of the subjects was 53.5+/-14.5 yrs. All the patients had moderate anaemia. There was a significant difference in the mean systolic and diastolic blood pressure, serum creatinine and serum urea values between males and females. The mean serum calcium levels were low. CONCLUSION: The present study is the first such study in this rural area and shows evidence of a relatively young population with ESRD having moderate anaemia and hypertension. There is evidence of hypocalcaemia and serum phosphorus is on the higher end of the normal range. These findings are usually associated with a higher risk of mortality. With the explosion of diabetes and hypertension in India, chronic kidney disease should be diagnosed and managed as early as possible if not prevented. PMID- 26557512 TI - Effect of Different Phases of Menstrual Cycle on Heart Rate Variability (HRV). AB - BACKGROUND: Heart Rate Variability (HRV), which is a measure of the cardiac autonomic tone, displays physiological changes throughout the menstrual cycle. The functions of the ANS in various phases of the menstrual cycle were examined in some studies. AIMS AND OBJECTIVES: The aim of our study was to observe the effect of menstrual cycle on cardiac autonomic function parameters in healthy females. MATERIALS AND METHODS: A cross-sectional (observational) study was conducted on 50 healthy females, in the age group of 18-25 years. Heart Rate Variability (HRV) was recorded by Physio Pac (PC-2004). The data consisted of Time Domain Analysis and Frequency Domain Analysis in menstrual, proliferative and secretory phase of menstrual cycle. Data collected was analysed statistically using student's pair t-test. RESULTS: The difference in mean heart rate, LF power%, LFnu and HFnu in menstrual and proliferative phase was found to be statistically significant. The difference in mean RR, Mean HR, RMSSD (the square root of the mean of the squares of the successive differences between adjacent NNs.), NN50 (the number of pairs of successive NNs that differ by more than 50 ms), pNN50 (the proportion of NN50 divided by total number of NNs.), VLF (very low frequency) power, LF (low frequency) power, LF power%, HF power %, LF/HF ratio, LFnu and HFnu was found to be statistically significant in proliferative and secretory phase. The difference in Mean RR, Mean HR, LFnu and HFnu was found to be statistically significant in secretory and menstrual phases. CONCLUSION: From the study it can be concluded that sympathetic nervous activity in secretory phase is greater than in the proliferative phase, whereas parasympathetic nervous activity is predominant in proliferative phase. PMID- 26557513 TI - Diurnal Variation in Peak Expiratory Flow and Forced Expiratory Volume. AB - INTRODUCTION: Diurnal variability in airways has most commonly been reported using peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). Characteristics of variability in small, mid and large airways caliber are expected to be different but have not been studied. AIM: The aim of the study was to assess diurnal variation in small mid and large airways caliber using FEF25, FEF50, FEF75 and FEF25-75 along with PEF and FEV1 in healthy subjects. MATERIALS AND METHODS: Spirometry was performed in 161 healthy subjects twice in a day. Diurnal variability in FEF25, FEF50, FEF75, FEF25-75, PEF and FEV1 were determined and compared. RESULTS: It revealed that all parameters exhibit significant diurnal variability. Diurnal variability is highest in large airways and lowest in smaller airways. CONCLUSION: Proximal airways show greater diurnal variation in their caliber than distal airways as reflected by greater variability in PEF as compared to FEV1. PMID- 26557514 TI - Heart Rate Variability in Adolescents - Normative Data Stratified by Sex and Physical Activity. AB - BACKGROUND: Heart rate variability (HRV) refers to the beat-to-beat fluctuations in the cardiac rhythm occurring due to modulation of the pacemaker (sinoatrial node) activity of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. Nowadays, cardiovascular diseases and their risk factors are increasingly occurring at a younger age (children and adolescents) and recording of HRV in them will help us to identify cardiovascular autonomic derangement earlier. However, to be used clinically, normative data has to be established in this age group considering other major factors that can influence HRV such as sex, physical activity, and BMI. MATERIALS AND METHODS: Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology has provided the standards for measurement of heart rate variability and we have followed the same. In the present study, we have described the normative data for HRV in the adolescent in the age group of 12-17 years, stratified based on sex and physical activity. RESULTS: Data given below are expressed as median with interquartile range (Median (IQR)) in the following order: non-athlete girls, non athlete boys, athlete girls and athlete boys. Time domain indices - SDNN - 66.35 (40.78), 63.20 (36.20), 113.00 (31.40) and 94.20 (35.55); RMSSD - 69.00 (50.55), 58.70 (43.40), 94.90 (42.10) and 100.30 (47.50); NN50 - 137.50 (100.25), 116.00 (90.50), 137.00 (81.00) and 156.00 (81.50). The frequency domain indices - LF power 1015.00 (1098.75), 945.00 (831.00), 1465 (642.25), and 1211.00 (811.37); HF power - 1324.00 (1707.00), 988.00 (1426.50), 2409.00 (1387.50), and 2219.00 (1752.00); Total power - 3374.50 (3094.25), 2757.00 (2641.00), 5202.00 (2501.50) and 5273.00 (3507.50); LFnu - 45.44 (16.61), 47.63 (29.98), 38.59 (11.81) and 37.10 (11.21); HFnu - 54.56 (16.61), 52.37 (29.98), 61.41 (11.81) and 62.90 (11.21). CONCLUSION: We have given sex and physical activity stratified HRV normative data for adolescents in the age between 12-17 years. PMID- 26557515 TI - Methicillin Resistant Staphylococcus aureus: Inconsistencies in Vancomycin Susceptibility Testing Methods, Limitations and Advantages of each Method. AB - BACKGROUND: Vancomycin may be ineffective against an increasing proportion of methicillin resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MICs) well within the susceptible range. On the other hand it is common knowledge that determination of vancomycin MICs is method dependent. Therefore, given the apparent variability in vancomycin MIC results obtained with the different methods, the use of the vancomycin MIC to predict the outcome of serious S. aureus infections needs to take into account the method used and the results of studies using that particular method. AIM: Comparative study was carried out to evaluate the MICs obtained by BMD method, E-test, and Vitek 2 method and to detect inconsistencies in these vancomycin for 66 MRSA isolates obtained from various samples of patients attending the OPDs & IPDs within a period of one year. MATERIALS AND METHODS: A comparative study was carried out to evaluate the MICs obtained by BMD method, E-test, and Vitek 2 method to detect vancomycin susceptibility in 66 clinical isolates of MRSA obtained from various samples of patients attending the OPDs & IPDs within a period of one year. The study was conducted in Department of Microbiology, Subharti Medical College, Meerut from January to December 2012. RESULTS: On determination of MICs for vancomycin for the MRSA isolates, all were identified as VSSA by BMD, E-Test & Vitek 2 methods. However, the vancomycin MIC values obtained by E-test correlated better with BMD method (correlation factor= 0.6727) than Vitek 2 (correlation factor=0.5316), indicating E-Test to be a better method for determination of vancomycin MICs as compared to Vitek 2. CONCLUSION: MRSA isolates with higher vancomycin MICs, even within the susceptibility range, are being observed more frequently which result in treatment failures with vancomycin. Because of the discrepancy that exists in vancomycin MIC results from different methods, the prediction of outcome of serious S.aureus infections should take into account the method used & results of studies using that particular method. PMID- 26557516 TI - Comparison of Antimicrobial Efficacy of Triclosan- Containing, Herbal and Homeopathy Toothpastes- An Invitro Study. AB - BACKGROUND: Use of antimicrobial agents is one of the important strategies to prevent oral diseases. These agents vary in their abilities to deliver preventive and therapeutic benefits. OBJECTIVES: This invitro study was conducted to assess antimicrobial efficacy of different toothpastes against various oral pathogens. MATERIALS AND METHODS: A total of nine toothpastes in three groups were tested for their antimicrobial activity against Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Streptococcus mutans (ATCC 0266P) and Candida albicans (Laboratory Strain) by modified agar well diffusion method. Statistical Analysis was performed using Minitab Software. A p-value of less than 0.05 was considered significant. RESULTS: Triclosan-based dental formulation with combination of fluoride (1000ppm) exhibited higher antimicrobial activity against test organisms than the combination of lower fluoride-concentration or sodium monofluorophosphate. Among herbal dentifrices, formulation containing Neem, Pudina, Long, Babool, Turmeric and Vajradanti showed significant antimicrobial activity against all the four tested microorganisms (p<0.05). However, against Streptococcus mutans, all three herbal products showed significant antimicrobial activity. Homeo products showed least antimicrobial activity on the tested strains. Formulation with kreosotum, Plantago major and calendula was significantly effective only against Streptococcus mutans. CONCLUSION: In the present study, antimicrobial activity of the toothpaste containing both triclosan and fluoride (1000ppm) as active ingredients showed a significant difference (p< 0.05) against all four tested microflora compared to that of with lower fluoride concentration or sodium monofluorophosphate. Of herbal groups, the only dentifrice containing several phytochemicals was found to be significantly effective and comparable to triclosan-fluoride (1000ppm) formulation. Thus, this herbal toothpaste can be used as alternative to triclosan-based formulations. However, these results might not be clinically useful unless tested invivo. PMID- 26557517 TI - Screening for Mupirocin Resistance in Staphylococcus. AB - INTRODUCTION: Mupirocin is widely used topical antibiotic for the treatment of skin and soft tissue infections caused by Staphylococcus and Streptococcus. In addition nasal formulations are approved for the use in nasal eradication of methicillin-resistant Staphylococcus aureus in patients and health care workers. Wide usage of mupirocin has resulted in resistance leading to treatment failure. AIM: To screen for the mupirocin resistance among the Staphylococcus isolates using disc diffusion and minimum inhibitory concentration method. MATERIALS AND METHODS: A cross-sectional study was done at Microbiology Department of Sri Ramachandra University with 100 strains of Staphylococcus spp isolated from skin and soft tissue infections. Methicillin susceptibility was done by disc diffusion method using oxacillin (1 MUgm) and cefoxitin (30 MUgm) discs. Isolates were screened for mupirocin resistance by disc diffusion method using 5 MUgm discs. High level and low level resistance determined by MIC using agar dilution method. RESULTS: In 100 Staphylococcus spp 56 were Staphylococcus aureus and 44 were CoNS. Among the 56 Staphylococcus aureus 49 (87.5%) were mupirocin susceptible and 7 (12.5%) resistant by 5MUg disc diffusion method. However by MIC method 11 (19.6%) were high and low level mupirocin resistant. Out of 44 CoNS 22 (50%) and 18 (41%) were susceptible by disc diffusion and MIC method respectively. Of the 26 resistant CoNS low level and high level mupirocin resistant was observed in 7 (15.9%) and 19 (43.1%) respectively. CONCLUSION: Screening for mupirocin resistance by disc diffusion method is important before attempting decolonisation. Mupirocin resistance is more with CoNS. Disc diffusion method may miss low level Mupirocin resistance. PMID- 26557518 TI - Candiduria in Catheter Associated Urinary Tract Infection with Special Reference to Biofilm Production. AB - INTRODUCTION: Urinary tract infections as a result of Candida species are becoming increasingly common in hospital settings. The association is higher in patients with prolonged urinary catheterization and also various pre-disposing factors. AIM: This study was done to look into the significance of candiduria in the catheterized patients and to perform microbial catheterization of yeast and biofilm detection by tube method to guide treatment protocol. MATERIALS AND METHODS: This is a prospective study. One hundred urine samples were collected over a period of 3 months. Specimens included were those of patients presenting with nosocomial Urinary tract infection (UTI) after 72 hours of hospitalization. The urine samples obtained were immediately processed in microbiology laboratory by semi-quantitative method as per standard protocol. All yeast isolates were stored for further microbial characterization. Biofilm production was detected by tube method. RESULTS: In the present study we observed that out of 100 samples obtained from catheterized patients presenting with nosocomial UTI 26% were caused by Candida species. Among the 26 Candida isolates 16 (61.53%) were non albicans Candida and 10(38.47%) were Candida albicans. Out 26 Candida isolates, 14(53.84%) of the candida isolates were found to produce biofilm. Biofilm production was found to occur more frequently among non albicans Candida 10(62.5%) than Candida albicans 4(40.0%). CONCLUSION: The present study reiterates the presence of candiduria in catheterized patients. Non-albicans candida speices are replacing candida albicans as the predominant pathogen for nosocomial UTI. It was also observed that Biofilm formation is seen more frequently with non albicans candida species than with Candida albicans. PMID- 26557519 TI - Bacteriological Quality of Treated Water and Dialysate in Haemodialysis Unit of A Tertiary Care Hospital. AB - INTRODUCTION: Haemodialysis is one of the treatment modalities for patients suffering from end stage renal disease (ESRD). Dialysis patients are exposed to large volumes of water for production of dialysis fluids. Treated water and dialysate come in direct contact with the patient's bloodstream. Such patients suffer from abnormalities of the immune system, making them more susceptible to infections. Microbial contamination of the treated water and dialysate can lead to biofilm formation and release of endotoxins in Haemodialysis system. These can give rise to pyrogenic reactions in the short term and beta2 amyloidosis, atherosclerosis, and increased mortality in the long term. AIM: To assess the bacteriological quality of treated water and dialysate used in the Haemodialysis unit of a tertiary care hospital. MATERIALS AND METHODS: A retrospective review of records of treated water and dialysate samples sent to the Microbiology laboratory for analysis of bacteriological contamination of the water used in haemodialysis treatment from January 2013 to June 2014 was conducted. The acceptable limits for treated water and dialysate were taken as <200 CFU/ml and < 2000 CFU/ml respectively as per Government of India Guidelines for Maintenance Haemodialysis. RESULTS: Thirty six samples of treated water and 394 samples of dialysate were analysed for bacteriological contamination. 4 out of 36 (11.1%) samples of treated water and 44 out of 394 dialysate samples (11.2%) showed unacceptable bacteriological growth. CONCLUSION: Regular and continual monitoring of the disinfection protocol of the water distribution system in haemodialysis unit is necessary to get good microbiological quality of treated water and dialysate fluid. PMID- 26557521 TI - Primary Bacteremia Caused by Rhizobium radiobacter in Neonate: A Rare Case Report. AB - Rhizobium radiobacter is a gram-negative tumourigenic plant pathogen that rarely causes infections in humans. Rhizobium radiobacter has a strong predilection to cause infection particularly in those patients who have long standing indwelling foreign devices. Herewith we report a rare case of Rhizobium radiobacter bacteremia in a new born baby without other risk factors. The patient was successfully treated with gentamicin and imipenem. To the best of our knowledge this is the first documented case of R. radiobacter from India causing neonatal infection. PMID- 26557520 TI - Bacteriological Profile of Surgical Site Infections and Their Antibiogram: A Study From Resource Constrained Rural Setting of Uttarakhand State, India. AB - INTRODUCTION: Surgical site infections (SSI) constitute a major public health problem worldwide and are the second most frequently reported nosocomial infections. They are responsible for increasing the treatment cost, length of hospital stay and significant morbidity and mortality. AIM: To determine the incidence of SSIs and the prevalence of aerobic bacterial pathogens involved with their antibiogram. MATERIALS AND METHODS: Samples were collected using sterile cotton swabs from 137 patients clinically diagnosed of having SSIs and were processed as per standard microbiological techniques. Antimicrobial susceptibility testing was done using modified Kirby-Bauer disc diffusion method. This cross sectional study was conducted for a period of six months (January 2013 to June 2013) in the Department of Microbiology at a rural tertiary care hospital of Uttarakhand state, India. RESULTS: Out of 768 patients, 137 (17.8%) were found to have SSIs and samples were collected from them. Out of total 137 samples, 132 (96.4%) yielded bacterial growth and 139 bacterial isolates were obtained. Staphylococcus aureus (50.4%) was the commonest organism followed by Escherichia coli (23.02%), Pseudomonas aeruginosa (7.9%) and Citrobacter species (7.9%). Antimicrobial profile of gram positive isolates revealed maximum sensitivity to vancomycin, teicoplanin and linezolid, whereas among gram negative isolates meropenem, piperacillin-tazobactam, and amikacin were found to be most sensitive. CONCLUSION: The rate of SSI observed in this study was comparable to other similar studies, however we observed a higher degree of antimicrobial resistance. Adherence to strict infection control measures, maintenance of proper hand hygiene and optimal preoperative, intraoperative and postoperative patient care will surely reduce the incidence of SSIs. PMID- 26557522 TI - Simplified Protocol for the Phenotypic Identification of Carbapenem Resistance Mechanism in Enterobacteriaceae. PMID- 26557523 TI - Scrub Typhus Seroprevalence in Healthy Indian Population. AB - Scrub typhus, a zoonosis caused by Orientia tsutsugamushi, is an important cause of acute febrile illness in India. This preliminary study determines the seroprevalence of scrub typhus in healthy Indian adults by measuring IgM and IgG antibodies to scrub typhus by ELISA in 100 healthy blood donors. Our study demonstrates a 15% seroprevalence of scrub typhus in adults. Further studies are needed to confirm these findings especially in children. PMID- 26557524 TI - Quest for An Ideal, Simple and Cost-Effective Stain for Morphological Assessment of Sperms. AB - BACKGROUND: Recent alarming trends of a substantial rise in the number of cases of infertility with as many as 30-40% being attributed to male-factor associated causes have created a need for further studies and advancements in semen analysis. Despite the focus on semen analysis over the years, assessment of sperm morphology has not been given due importance although it is a simple, standard and baseline diagnostic modality. It can be used to predict the need and outcome of Artificial Reproductive Techniques such as Invitro Fertilization, Gamete Intra Fallopian Tube Transfer and Intra Cytoplasmic Sperm Injection. AIM: To find the ideal, simple and cost-effective basic stain for assessment of sperm morphology in a rural tertiary care set- up where advanced equipment for assessment of sperm morphometry are inaccessible. MATERIALS AND METHODS: An updated way of determining sperm shape is called the Kruger's strict morphology method. Keeping this as the standard criterion, we studied semen samples of 62 healthy male subjects using four basic staining techniques and the consensus of four independent observers was tabulated. RESULTS: We found that Haematoxylin and Eosin stain was the best stain for assessment of sperm head morphology. Rapid Papanicolau stain was the most ideal, simple and cost-effective stain for overall assessment of sperm morphology. CONCLUSION: Sperm morphology assessment remains the baseline necessity for the diagnosis and management of male factor associated infertility when advanced techniques are unavailable, inaccessible or unaffordable. PMID- 26557526 TI - Plasmacytoid Myoepithelioma of the Hard Palate in a Child - A Rare Case Report. AB - Myoepithelioma is a rare tumour accounting for 1-1.5% of salivary gland tumours, 21% of which occur in soft & hard palate. Cytologic features of these tumours are not well established leading to diagnostic pitfall in many cases on FNAC. However, as radiologic findings are overlapping and inconclusive in salivary gland tumours, preoperative cytologic diagnosis may help surgeons to plan surgery especially in patients requiring facial surgery. Here, we present a rare case of plasmacytoid myoepithelioma of the hard palate in an 11-year-old boy which was conclusively diagnosed on FNAC and further confirmed by histopathological and immunohistochemical studies. We have made an attempt to describe cytologic features of myoepithelioma with differential diagnosis of these tumours through review of literature. PMID- 26557527 TI - Trichinella spiralis: Mere Co-Existence or Carcinogenic Parasite For Oral Squamous Cell Carcinoma? AB - Trichinella spiralis is a parasite which is usually seen in pork-eaters. Most of the trichinosis infections cause little or no symptoms. We report a rare case of a middle aged North Indian male who presented with a painless ulcer in right buccal mucosa which was biopsied and reported as squamous cell carcinoma. Wide local excision was done subsequently which showed encysted larvae of Trichinella spiralis in the deeper skeletal muscle bundles. This article supports the carcinogenic potential of trichinosis and suggests timely work-up and treatment of the parasite. PMID- 26557525 TI - Malaria Diagnosis Using Automated Analysers: A Boon for Hematopathologists in Endemic Areas. AB - BACKGROUND: Haematological abnormalities are common in acute febrile tropical illnesses. Malaria is a major health problem in tropics. In endemic areas especially in the post monsoon season, it is not practical to manually screen all peripheral blood films (PBF) for malarial parasite. Automated analysers offer rapid, sensitive and cost effective screening of all samples. AIM: The study was done to evaluate the usefulness of automated cell counters analysing their histograms, scatter-grams and the flaggings generated in malaria positive and negative cases. The comparison of other haematological parameters were also studied which could help to identify malaria parasite in peripheral blood smear. MATERIALS AND METHODS: The blood samples were analysed using Beckman coulter LH 750. The abnormal scatter grams and additional peaks in WBC histograms were observed diligently & compared with normal controls. Haematological abnormalities were also evaluated. STATISTICAL ANALYSIS: Statistical analysis was done by using software Epi-Info version 7.1.4 freely available from CDC website. Fisher exact test was applied to calculate the p-value and value < 0.05 was considered as significant. Final identification of malarial parasite species was done independently by peripheral blood smear examination by two pathologists. RESULTS: Of all the 200 cases evaluated abnormal scatter grams were observed in all the cases of malaria while abnormal WBC histogram peaks were noted in 96% cases demonstrating a peak at the threshold of the histogram. The difference between number of slides positive for abnormal WBC scatter gram and abnormal WBC histogram peaks were statistically highly significant (p=0.007). So abnormal WBC scatter gram can better give idea of malarial parasite presence. Of the haematological parameters thrombocytopenia (92% cases) emerged as the strongest predictor of malaria. CONCLUSION: It is recommended for haematopathologists to review the haematological data and the scatter plots on the analyser along with peripheral blood smear examination. PMID- 26557528 TI - Intraneural Hybrid Neurofibroma/Schwannoma In Scalp: A Case Report. AB - Benign Peripheral Nerve Sheath Tumours (BPNSTs) are traditionally classified into schwannoma, neurofibroma and perinurioma. Due to advances in molecular techniques, hybrid BPNSTs containing more than one histologic types have been documented. Recent studies have demonstrated their frequent association with inherited syndromes like schwannomatosis and neurofibromatosis. Intraneural variant of hybrid neurofibroma/schwannoma is yet to be described. Here we report such a case in a 30-year-old male, who presented with a scalp swelling and histology showed intraneural neurofibromatous tumour admixed with schwannoma-like nodules. IHC (immunohistochemistry) showed variable S100 staining in neurofibromatous areas, diffuse S100 staining in schwannoma-like areas and negative EMA staining in the tumour. PMID- 26557529 TI - Intraparenchymal Angiomatous Meningioma: A Diagnostic Dilemma. AB - Meningioma arises from the arachnoid cap cells of the cerebrum. Intraparenchymal meningiomas or meningiomas without dural attachment are rare. We report a case of 40-year-old male who presented with a history of headache, dizziness and gradual loss of vision since one year. Clinicoradiological diagnosis of a high grade glioma was considered. Tumour was excised and haematoxylin and eosin stained sections revealed a tumour comprised predominantly of variable sized blood vessels showing hyalinization in a background of plump spindle cells with oval vesicular nuclei. In view of these features angiomatous meningioma was suspected. However, to confirm the diagnosis, a panel of immunohistochemical markers including vimentin, EMA and GFAP was done and a final diagnosis of angiomatous meningioma was offered. Angiomatous meningioma is a rare variant of meningioma and even much rarer in the intraparenchymal location. Angiomatous meningioma should be considered in the differential diagnosis of highly vascular intraparenchymal brain tumours. PMID- 26557530 TI - Serous Microcystadenoma of Pancreas. AB - Cystic tumours of the pancreas are less common, representing 5% to 10% of all pancreatic neoplasms. They constitute an important subset because many cystic tumour are either benign or low-grade (indolent) malignant neoplasm. Cystic lesions are also detected more commonly owing to the increased use of sensitive imaging techniques. A female patient 48-year-old, presented with upper abdominal symptoms. CT abdomen reveals a large multicystic mass with central scar shows no communication with pancreatic duct. Resected specimen, show a large lobulated mass with central scar and many small cysts. Microscopic examination confirms the diagnosis of serous adenoma. PAS positivity is used to demonstrate the glycogen content of the lining epithelium. PMID- 26557531 TI - Renal Myxoma- A Rare Variety of Benign Genitourinary Tumour. AB - Renal myxomas are rare neoplasms and very few cases have been reported in literature. Here we report a renal myxoma in a 48-year-old lady with hypothyroidism who presented with abdominal pain. She was found to have a mass lesion of 67 x 61 x 74 mm with exophytic component in the right kidney on ultrasonography and computed tomography. Right radical nephrectomy was performed due to suspicion of malignancy. Grossly the resected kidney showed a gelatinous, semi-translucent mass involving the mid and lower poles. Microscopy revealed marked hypocellular appearance of loose myxoid tissue with foamy histiocytes. Tumour cells were reactive for vimentin. At eight months of follow-up, patient is doing well. PMID- 26557532 TI - Ectopic Paratubal Adrenal Cell Rest Associated with Mucinous Cystadenoma of Ovary. AB - Ectopic adrenal cortex is a rare entity. Usually found in male children; commonly located around kidney, retroperitoneum, spermatic cord and para-testicular region. Rarely, adults with heterotopic adrenal glands are described. Incidence in females is very less; though sometimes detected accidentally in hysterectomy specimens. We describe a case of ectopic adrenal cortical cell in paratubal region in a patient with mucinous cyst adenoma of ovary. A 26-year-old female presented with complains of menstrual irregularities and abdominal discomfort for 6 months. Investigations suggested a right ovarian cyst. Right ovarian cystectomy with partial salpingectomy was performed; histopathology revealed mucinous cyst adenoma. Sections from tube showed presence of ectopic adrenal cortical rest in the paratubal region, incidentally discovered on microscopy. We present this case because of its rarity in females, interesting presentation with another unrelated gynaecological pathology, its potentiality for malignant transformation and possible complications. PMID- 26557533 TI - Microfilaria Coexistent with Fibroadenoma - An Unusual Association. AB - Filariasis is an endemic problem in India. Involvement of breast by filariasis is uncommon, but known to occur in endemic areas. However, microfilaria co-existing with neoplastic lesions is very rare. Here we report an unusual finding of microfilaria co-existing with fibroadenoma in a 20-year-old female patient. PMID- 26557534 TI - Reticulum vs Inclusions: A Learning Experience in Haemoglobin H Disease. AB - Haemoglobin H disease, also known as the alpha-thalassaemia is characterized by the presence of HbH inclusions in red blood cells, detectable on supra-vital stain. We present a case of a previously asymptomatic 31-year-old male, who insidiously developed anaemia and had prominent splenomegaly. Peripheral smear examination revealed microcytic hypochromic anaemia with numerous spherocytes and moderate polychromasia. In reticulocyte preparation with Brilliant cresyl blue, HbH inclusions were mistakenly identified as granulofilamentous reticulum of reticulocytes, giving a spuriously high reticulocyte percentage. After the literature review, repeat assessment was performed and with the aid of high performance liquid chromatography result, it was possible to delineate the HbH inclusions. PMID- 26557535 TI - Choriocarcinoma with Uterine Rupture and Shock: A Rare Case Report. AB - Choriocarcinoma is a rare neoplasm and a malignant form of gestational trophoblastic disease. Choriocarcinoma is frequently preceded by a complete mole, ectopic pregnancy, nonmolar intrauterine abortion, and uncommonly by a partial mole. It is treated medically with chemotherapeutic drugs usually. However, we managed to save a life with appropriate and timely surgical intervention in a case of choriocarcinoma who presented with uterine rupture, haemoperitoneum, anaemia and hypovolemic shock. The patient underwent exploratory laparotomy and hysterectomy followed by systemic chemotherapy. PMID- 26557536 TI - Gastric Glomus Tumour: A Rare Cause of Gastrointestinal Bleeding. PMID- 26557537 TI - Subcutaneous Fungal Cyst Masquerading as Benign Lesions - A Series of Eight Cases. AB - BACKGROUND: Subcutaneous fungal infections are caused by penetration of the causative fungi into the subcutaneous layer and are usually localised. We present a series of eight cases with subcutaneous fungal cystic lesions masquerading as benign lesions. MATERIALS AND METHODS: A retrospective study was conducted on subcutaneous fungal infections seen between January 2007 to July 2014 in the Department of Pathology. Eight patients with biopsy proven subcutaneous fungal infection were included. We collected and analysed their demographic, clinical and histopathological details. RESULTS: Among eight patients, six were male and two were female. The mean age was 47 years (Range: 21-70). All the eight patients presented with non-tender cystic swelling. The size of the swellings varied from a minimum of 3x3 cm to maximum of 10x4 cm. Out of eight, hand was involved in three, forearm in one, elbow in two, leg in one and foot in one. On H&E staining, all the cases showed fibro collagenous cyst wall, lined by histiocytes, granulomatous reaction, foreign body type of giant cells with acute and chronic inflammatory infiltrate containing fungal elements. Six were identified as hyalohyphomycosis and two were identified as phaeohyphomycotic cysts based on pigmentation of hyphae. CONCLUSION: Fungal infection should be suspected in all subcutaneous cystic lesions. Excised tissue should always be sent for culture and histopathology. PMID- 26557539 TI - Estimation of Stature From Hand and Foot Measurements in a Rare Tribe of Kerala State in India. AB - INTRODUCTION: The present study has been undertaken on the Vettuvar group of tribes in Kasargod district of Kerala state, and explores the usability of dimensions of hands and feet as predictors of stature in the tribal population of Kasargod District of Kerala, India. The present study is the first ever documented anthropological work on the tribes of Kasargod district, Kerala, India. MATERIALS AND METHODS: Two hundred subjects comprising of 100 males and 100 females in 20-30 years age group were included in the study group. Dimensions of hands and feet viz: hand length, hand breadth, foot length and foot breadth were measured independently on left and right side of each individual using a Sliding calliper. Stature of individuals was measured with the help of a Stadiometer. RESULTS: Statistical analysis indicated that the bilateral variations were insignificant for all the measurements except foot breadth among females (p<0.001). The paired sample t-test showed that the statistical difference between males and females was highly significant for all the measurements (p<0.001). The correlation between the stature and various parameters studied in males and females were found to be positive and statistically highly significant. Linear and multiple regression equation for stature estimation were calculated separately for males and females. CONCLUSION: The significant positive correlation between the study variables and the stature indicates that these variables can be successfully used to predict stature. PMID- 26557538 TI - Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy. AB - BACKGROUND AND OBJECTIVES: Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. RESULTS: Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. CONCLUSION: The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID- 26557540 TI - TASER((r)) Electronic Control Device-Induced Rhabdomyolysis and Renal Failure: A Case Report. AB - Many law enforcement agencies around the United States are employing the use of TASER((r)) electronic control devices (TASER((r)) International Inc.) to subdue combative suspects. Since its inception the TASER((r)) has had a temporal association with reports of rhabdomyolysis. Case reports have reported TASER((r)) induced rhabdomyolysis as mild but serious cases have also been reported. Herein we present the case of a single patient who was admitted to our health network with severe rhabdomyolysis after receiving TASER((r)) shocks and review the pertinent literature. No direct link has been established between clinically significant rhabdomyolysis and TASER((r)) device application but this case serves as an example of a sparsely documented but serious complication that may occur in patients who are at risk for restraint by an electronic control device. PMID- 26557541 TI - Medico Legal Consideration in Postmortem Diagnostic of Intracranial Haemorrhage. PMID- 26557543 TI - The Current Mental Health Status of Ebola Survivors in Western Africa. AB - The epidemic of Ebola virus disease has claimed many lives. The impact of this disease is evident in the mental health of the survivors. The mere drafting of policies will not help; rather execution at the ground level is essential. There is an urgent need, to focus on the ways by which the sufferings should be reduced. The present article throws light on this grave problem in Africa. PMID- 26557542 TI - "Why We Say No! A Look Through the Editor's Eye". AB - BACKGROUND: The rapidly flourishing health science has provided a ground to perform research work and contribute to the field of science. On the other hand, reporting the research is equally important as carrying out research. Many such researches and their ground breaking work remain unreported or do not reach the guild, because of poor drafting skills. In nine years since Journal of Clinical and Diagnostic Research (JCDR) inception, editorial have come across many manuscripts which are clinically and socially relevant in their message, but lack legible drafting. It was felt that an objective analysis of the reasons for rejection, of manuscripts, is required. AIM: The present study was conducted with the aim to determine the reasons for rejection of medical and dental manuscript submitted in JCDR. MATERIALS AND METHODS: Retrospective analysis of 1000 consecutive medical and dental articles submitted to JCDR since 1(st) August 2014 was done. Only those articles (902) that reached the end point on decision were considered. The reasons of rejection for medical and dental articles were enlisted and analyzed. When there were multiple reasons of rejection and all of them were critical, then they were counted in all the categories. RESULTS: Out of the 902 consecutive articles 522 articles underwent rejection. Among the rejected ones, dental specialty comprised of 43.5% and medical articles contributed 56.5%. The most frequent reasons for rejection were commonality (44.6%), non compliance by authors (17.8%), methodological issues (17.3%), plagiarism (11.1%), received same topic and published (7.66%), poor draft (6.70%), data inconsistency (5.77%), mismanagement (1.72%), blacklisted author (1.14%), ethical and out of scope were 0.57% each. CONCLUSION: Based on our findings, it can be concluded that manuscript rejection can be avoided by the authors, if the topic is well choosen and communication is maintained with the journal editorial. PMID- 26557544 TI - Competing Risk Approach (CRA) for Estimation of Disability Adjusted Life Years (DALY's) for Female Breast Cancer in India. AB - BACKGROUND: Competing Risk Approach (CRA) has been used to compute burden of disease in terms of Disability Adjusted Life Years (DALYs) based on a life table for an initially disease-free cohort over time. OBJECTIVE: To compute Years of Life Lost (YLL) due to premature mortality, Years of life lost due to Disability (YLD), DALYs and loss in expectation of life (LEL) using competing risk approach for female breast cancer patients for the year 2008 in India. MATERIALS AND METHODS: The published data on breast cancer by age & sex, incidence & mortality for the year 2006-2008 relating to six population based cancer registries (PBCR) under Indian Council of Medical Research (ICMR), general mortality rates of 2007 in India, published in national health profile 2010; based on Sample Registration System (SRS) were utilized for computations. Three life tables were constructed by applying attrition of factors: (i) risk of death from all causes ('a'; where a is the general death rate); (ii) risk of incidence and that of death from causes other than breast cancer ('b-a+c'; where 'b' is the incidence of breast cancer and 'c' is the mortality of breast cancer); and (iii) risk of death from all other causes after excluding cancer mortality ('a-c'). Taking the differences in Total Person Years Lived (TPYL), YLD and YLL were derived along with LEL. RESULTS: CRA revealed that the DALYs were 40209 per 100,000 females in the life time of 0-70+ years with a LEL of 0.11 years per person. Percentage of YLL to DALYs was 28.20% in the cohort. CONCLUSION: The method of calculation of DALYs based on the CRA is simple and this will help to identify the burden of diseases using minimal information in terms of YLL, YLD, DALYs and LEL. PMID- 26557545 TI - Major Delays in the Diagnosis and Management of Tuberculosis Patients in Nepal. AB - BACKGROUND: Early diagnosis is a determining factor for spread of tuberculosis. Delay in diagnosis and treatment of tuberculosis geometrically increases spread and infectivity of the disease and is associated with higher risk of mortality. AIM: The present study aimed to investigate the length of delays in diagnosis and treatment among new pulmonary tuberculosis patients in central development region of Nepal. MATERIALS AND METHODS: A cross-sectional study was conducted by administration of structured questionnaire interview and reviewing the medical records of the new sputum smear positive pulmonary tuberculosis cases during January-May 2015. Simple random sampling was applied to select samples from 5 districts of 19 districts comprising at least one each from 3 ecological regions of Nepal. RESULTS: A total of 374 new sputum smear positive pulmonary tuberculosis cases were included in the study. The median patient delay, health system delay, and total delay were 32 days, 3 days and 39.5 days respectively. The unacceptable patients delay was 53.21% (95% CI: 48.12-58.29) of all new patients, whereas it was 26.74% (95% CI: 22.23-31.24) for the unacceptable health system delay and the unacceptable total delay was 62.83% (95% CI: 57.91-67.75). CONCLUSION: TB diagnosis and treatment is still a significant problem of Nepal. Majority of unacceptable delays were from patients. Identifying factors influencing delays and developing evidence-based approaches to address those delays will help in advancing tuberculosis prevention and management in low income settings. PMID- 26557546 TI - Hepatitis C Seroprevalence and Risk Factors in Adult Population of Chaharmahal and Bakhtiari Province of Iran in 2013. AB - INTRODUCTION: Hepatitis C is the second leading viral infectious disease worldwide. In Iran, hepatitis C is the most important and prevalent reason for chronic hepatitis and liver cirrhosis in the multi transfused population. AIM: This study was conducted to determine seroprevalence and burden of hepatitis C in Chaharmahal and Bakhtiari province and to plan for controlling it. MATERIALS AND METHODS: For this analytical, population-based study, 3000 samples were older than 15 years old and were enrolled from urban and rural areas of Chaharmahal and Bakhtiari province, southwest Iran per cluster sampling. Written informed consent was obtained from the participants and the demographic data, transmission route and risk factors were collected after blood sample taking. Hepatitis C virus antibody (HCV Ab) and western blotting were consecutively run. STATISTICAL ANALYSIS: Data analysis was done by SPSS 19 using descriptive statistics, and chi square test, Fisher's exact test, and logistic regression Ap value of 0.05 was considered as the level of significance. RESULTS: The prevalence of HCV Ab was obtained 1.4% (95% CI, 0.95-1.7) and that of positive hepatitis C by western blotting 0.9% (95% CI, 0.65-1.3). The prevalence in men (1.2%) was obtained two times higher than women. The highest prevalence was obtained in 35 to 44-year-old population (2%). The prevalence was higher in married individuals and less in higher educated. History of hospital stay, first degree relatives infected with HCV, jaundice, history of blood transfusion, tattoo, outpatient surgery, imprisonment, contact with the infected, intravenous (IV) drug abuse, and smoking had significant association with disease prevalence (p<0.05). The highest odds ratio was obtained for history of IV drug abuse (OR=38.2, 95% CI, 14.06-103.9) followed by imprisonment (OR=8.9, 95% CI, 2.97-26.6). However, by logistic regression only history of IV drug abuse was obtained as significant (p<0.05). CONCLUSION: Hepatitis C is growing and emerging as the most prevalent chronic, viral hepatic disease, so further consideration of risk factors and routes of transmission is crucial for appropriate planning for, and preventing, treating, and controlling hepatitis C. IV drug abusers as the most important group need special consideration and surveillance in order to cut infection chain and decrease the disease incidence. PMID- 26557547 TI - Study of the Continuous Improvement Trend for Health, Safety and Environmental Indicators, after Establishment of Integrated Management System (IMS) in a Pharmaceutical Industry in Iran. AB - BACKGROUND: Nowadays, organizations try to improve their services and consequently adopt management systems and standards which have become key parts in various industries. One of these management systems which have been noticed in the recent years is Integrated Management System that is the combination of quality, health, safety and environment management systems. AIM: This study was conducted with the aim of evaluating the improvement trend after establishment of integrated management system for health, safety and environment indicators, in a pharmaceutical industry in Iran. MATERIALS AND METHODS: First, during several inspections in different parts of the industry, indicators that should have been noted were listed and then these indicators were organized in 3 domains of health, safety and environment in the form of a questionnaire that followed Likert method of scaling. Also, the weight of each index was resulted from averaging out of 30 managers and the viewpoints of the related experts in the field. Moreover, by checking the documents and evidence of different years (5 contemplation years of this study), the score of each indicator was determined by multiplying the weight and score of the indices and were finally analysed. RESULTS: Over 5 years, scores of health scope indicators, increased from 161.99 to 202.23. Score in the first year after applying the integrated management system establishment was 172.37 in safety part and in the final year increased to 197.57. The changes of environmental scope rates, from the beginning of the program up to the last year increased from 49.24 to 64.27. CONCLUSION: Integrated management systems help organizations to improve programs to achieve their objectives. Although in this study all trends of health, safety and environmental indicator changes were positive, but at the same time showed to be slow. So, one can suggest that the result of an annual evaluation should be applied in planning future activities for the years ahead. PMID- 26557548 TI - Thyroidectomy Under Regional Anaesthesia: An ORL Perspective. AB - BACKGROUND: The use of regional anaesthesia as an effective alternative to general anaesthesia in thyroid surgeries is now being accepted in many parts of the world. In this day of computers and technology, there is an increased awareness among the people of the available options of anaesthesia and the adverse effects of general anaesthesia. They thus have an inclination to avoid general anaesthesia wherever feasible. This study dwells on the use of regional anaesthesia as an alternative tool that can be offered to the patients undergoing thyroidectomy. AIMS: This study aims at analysing the effectiveness, safety, ease and patient acceptability of performing thyroidectomies under regional anaesthesia. SETTINGS AND DESIGN: This prospective study was performed at a university - affiliated hospital. MATERIALS AND METHODS: Twenty nine patients who underwent thyroidectomy for benign thyroid diseases under regional anaesthesia were included in this study: 20 patients under deep cervical plexus block and 9 patients under cervical epidural anaesthesia. STATISTICAL ANALYSIS USED: Z-test and validity test. RESULTS: In our study, all the 29 patients who underwent thyroidectomy under regional anaesthesia found the anaesthesia effective and were comfortable throughout the procedure. The surgeon too was at ease while performing the surgery. No complications were recorded. CONCLUSION: In our present study, regional anaesthesia (Cervical epidural anaesthesia and Cervical plexus block) has been used safely and effectively in 29 thyroid surgeries. We conclude that although regional anaesthesia has been reserved for high risk thyroidectomies it may be offered as effective alternative to general anaesthesia even in routine thyroid surgeries. PMID- 26557549 TI - Modified External Dacryocystorhinostomy in Primary Acquired Nasolacrimal Duct Obstruction. AB - BACKGROUND: Epiphora secondary to acquired nasolacrimal duct obstruction is a common ophthalmic problem in adults requiring surgical management. External dacryocystorhinostomy (DCR) is a reliable but difficult surgical technique for the treatment of nasolacrimal duct obstruction. PURPOSE: To evaluate the success rate and complications of modified external DCR in patients with primary acquired nasolacrimal duct obstruction. MATERIALS AND METHODS: This hospital based prospective interventional study included 56 patients with primary acquired nasolacrimal duct obstruction. Diagnosis of nasolacrimal duct obstruction was made through irrigation of the nasolacrimal drainage system. All patients were operated by modified technique of external DCR with anastomosis of the anterior lacrimal and nasal mucosal flaps only, whereas posterior mucosal flaps were excised. Patients were followed up for a period of 6 months. During the follow up, success rate and complications if any were recorded. Success was defined objectively by a patent lacrimal passage on irrigation and subjectively by the absence of watering or discharge. RESULTS: The mean age of the study population was 39.23 +/- 10.66 years, and 78.6% of patients were females (male to female ratio 1:3.7). The average operation time was 36.48 +/- 4.72 minutes. Objective and subjective success rates were 92.9% and 89.3%, respectively after a follow up period of 6 months. Intraoperatively, haemorrhage occurred in 3 patients (5.3%) and laceration of the nasal mucosa in 4 patients (7.1%). Postoperative complications included significant lid swelling and periorbital ecchymosis in 3 patients (5.3%), epistaxis in 2 patients (3.6%) and hypertrophic scar in 2 patients (3.6%). CONCLUSION: These results suggest that modified external DCR with anterior flaps anastomosis only is a simple, safe, less time consuming surgical technique that is easy to perform, and the outcome is comparable to conventional DCR. PMID- 26557550 TI - Effect of Oral Lactoferrin on Cataract Surgery Induced Dry Eye: A Randomised Controlled Trial. AB - CONTEXT: Cataract surgery is one of the most frequently performed intra-ocular surgeries, of these manual Small Incision Cataract Surgery (SICS) is a time tested technique of cataract removal. Any corneal incisional surgery, including cataract surgery, can induce dry eye postoperatively. Various factors have been implicated, of which oneis the inflammation induced by the surgery. Lactoferrin, a glycoprotein present in tears is said to have anti-inflammatory effects, and promotes cell growth. It has been used orally in patients of immune mediated dry eye to alleviate symptoms. AIM: This study was aimed to evaluate the dry eyes induced by manual Small Incision Cataract Surgery, and the effect if any, of oral lactoferrin on the dry eyes. SETTINGS AND TRIAL DESIGN: A single centre, prospective randomised controlled trial with a concurrent parallel design. The study was carried out on patients presenting in the OPD of Rohilkhand Medical College hospital for cataract surgery. MATERIALS AND METHODS: Sixty four patients of cataract surgery were included in the study. Patients with pre-existing dry eyes, ocular disease or systemic disease predisposing to dry eyes were excluded from the study. The selected patients were assigned into two groups by simple randomisation-Control Group A-32 patients that did not receive oral lactoferrin postoperatively. Group B-32 patients that received oral lactoferrin 350 gm postoperatively from day 1 after SICS. All patients were operated for cataract and their pre and postoperative (on days 7, 14, 30 and 60) dry eye status was assessed using the mean tear film break-up time (tBUT) and Schirmer test 1 (ST 1) as the evaluating parameters. Subjective evaluation of dry eye was done using Ocular Surface Disease Index (OSDI) scoring. Data was analysed for 58 patients, as 6 did not complete the follow up. STATISTICAL ANALYSIS: Unpaired t-test was used to calculate the p-values. RESULT: There was a statistically significant difference between the tBUT values of the Control and Lactoferrin group from day 14 onwards. The tBUT of control group on day 60 was 7.86 (+/-0.86) seconds as compared to 13.9(+/- 0.99) seconds in the lactoferrin group. The Schirmer test 1 values also showed a statistically significant difference between the two groups- 15.86 (+/- 5.83) seconds in the control group versus 30.9 (+/-1.66) in the lactoferrin group on day 60. OSDI score showed 42.8% patients complaining of at least mild dry eye symptoms in the control group, as compared to 26.6% patients in the lactoferrin group on day 60. CONCLUSION: Small Incision Cataract Surgery induces dry eye postoperatively. Oral lactoferrin given postoperatively improves tear film status and dry eye after cataract surgery. PMID- 26557551 TI - Clinical Evaluation of Correlation Between Diabetic Retinopathy with Modifiable, Non-Modifiable and Other Independent Risk Factors in Tertiary Set-up in Central Rural India. AB - INTRODUCTION: Diabetes mellitus and its related ocular complication like diabetic retinopathy (DR) are showing increased prevalence in India, but the magnitude of presence and progression of DR in central rural population and its relation to certain variables requires further exploration. AIM: To study the demographic profile on diabetic retinopathy and the association between different risk factors of diabetic retinopathy with its onset and severity. MATERIALS AND METHODS: A cross-sectional study was carried out on patients suffering from diabetes mellitus (n=100) admitted to AVBRH, Sawangi (Meghe) in a duration of 2 months from April to June 2014. Snellen's chart, slit lamp, and indirect ophthalmoscope were used for ocular examination of all patients. Comprehensive examination was used for risk factor assessment. STATISTICAL ANALYSIS: All data was entered into the proforma. Chi-square test, Student's unpaired t-test and one way ANOVA using SPSS 17.0 and Graph Pad Prism 5.0. (p<0.05 was considered significant). RESULTS: The study showed that among all the diabetics (mean age 56.4+11.2 years), 68% were males and 97% type 2 diabetics. This study showed statistically significant association between serum triglyceride (p=0.0003), duration since diagnosis of diabetes mellitus (p=0.0006), serum total cholesterol (p=0.0021), FBG (p=0.003), serum HDL (p=0.012) and hypertension (p=0.045) with presence of diabetic retinopathy. The study also revealed that serum triglycerides (p=0.001), serum total cholesterol (p=0.006), BMI (p=0.04) and duration of diabetes (p=0.04) are the only factors which showed significant association with the severity of diabetic retinopathy. CONCLUSION: Effective screening strategies for early detection of both diabetes and diabetic retinopathy should be formulated especially for the rural population which is not aware about the various complications of diabetes and their final outcomes. Diabetics should follow proper guidelines to prevent or delay progression of DR. PMID- 26557552 TI - Morning Glory Disc Anomaly, A Report of a Successfully Treated Case of Functional Amblyopia. AB - Morning Glory Disc Anomaly (MGDA) is a congenital malformation of the optic nerve characterized by the presence of a funnel-shaped macropapilla with neuroglial remnants in its center surrounded by an elevated and pigmented chorioretinal ring. Its incidence is rare and no gender predisposition has been found. Associated conditions like strabismus lead to an early diagnosis. We report the case of a 3.8-year-old boy with amblyopia of the right eye (count fingers 0.3 meters) due to MGDA. Correction of the refractive error with glasses, along with occlusive therapy resulted in a visual acuity of 20/100 after a five-year follow up. The presence of amblyopia in these cases demands an early management oriented to improve the visual acuity. Every patient with an anatomical malformation diagnosed during the period of sensory maturation should be treated with occlusive therapy and followed on a regular basis to diagnose associated conditions such as retinal detachment. We recommend occlusive therapy in every patient diagnosed with MGDA or in any patient with unilateral or asymmetric structural abnormalities that could lead to amblyopia. This 5-year case follow-up provides additional evidence of the importance of treatment during the period of amblyopia reversibility. PMID- 26557553 TI - Analysis of Vascular Access in Haemodialysis Patients - Single Center Experience. AB - BACKGROUND: Vascular access is the key in successful management of chronic haemodialysis (HD) patients. Though native arteriovenous fistula (AVF) is considered the access of choice, many patients in our country initiate haemodialysis through central venous catheter (CVC). There is paucity of data on vascular access in haemodialysis patients from southern India. AIM: Aim of the present study was to review our experience of vascular access in Haemodialysis patients (both central venous catheters and arteriovenous fistula) and to assess its success rate and common complications. MATERIALS AND METHODS: This prospective study was conducted between January 2014 and December 2014 in our institute. A total of 50 patients with Chronic Kidney Disease (CKD) underwent vascular access intervention during the above period. RESULTS: A temporary venous catheter (96%) in the right internal jugular vein was the most common mode of initiation of haemodialysis with 34.48% incidence of catheter related sepsis. Fifty percent of catheters were removed electively with mean duration of catheter survival of 77.23 +/- 14.8 days. Wrist AVF (60%) was the most common site of AVF creation followed by arm (30%), mid-forearm (7.5%) and leg (2.5%). Complications include distal oedema (17.5%) and venous hypertension (2.5%). Primary failure occurred in 25% of patients and was more common in diabetic, elderly (>60 years) and in distal fistulas. Elderly patients (>60 years) starting dialysis with a CVC were more likely to be CVC dependent at 90 days. CONCLUSION: Late presentation and delayed diagnosis of chronic kidney disease (CKD) necessitates dialysis initiation through temporary catheter. Dialysis catheter with its attendant complications further adds to the morbidity, mortality, health care burden and costs. Early nephrology referral and permanent access creation in the pre dialysis stage could avert the unnecessary complications and costs of catheter. PMID- 26557554 TI - Clinical Profile and Predictors of Outcomes in Older Inpatients with Pyelonephritis in a Tertiary Care Hospital in Southern India. AB - BACKGROUND: Pyelonephritis is a serious infection associated with significant morbidity and mortality in the elderly with an estimated annual incidence rate of around 10% from previous studies. Older people are at a higher risk for pyelonephritis due to multiple factors including structural, functional and co existent conditions. There is very little data on the incidence, clinical features and outcomes among elderly patients with pyelonephritis in India. MATERIALS AND METHODS: We performed a retrospective review of case records of 100 consecutive patients over the age of 60 years with pyelonephritis admitted to a tertiary care hospital. RESULTS: One fourth of our patients (26%) did not have fever, 49% had delirium and 52% had systemic inflammatory response syndrome (SIRS). Sixty five percent of the patients were diabetic and 60% had infections caused by extended spectrum beta lactamase (ESBL) producing organisms. As in other studies, the commonest organism isolated was E.coli (49%). A low serum albumin level was a predictor of mortality (p<0.001) and increased length of hospital stay (p<0.005). Delirium was also associated with a poor outcome (p=0.009) in these patients. Patients with pyelonephritis secondary to ESBL producing organisms had a higher length of stay (p<0.005). CONCLUSION: Hypoalbuminemia and delirium predicted poor outcomes in our patients. We found a high prevalence of ESBL infections in this study. Further research is required to assess the efficacy of aggressive management of delirium and low albumin in improving health and cost outcomes. PMID- 26557555 TI - Early Menopause in Type 2 Diabetes - A Study from a South Indian Tertiary Care Centre. AB - INTRODUCTION: Menopause marks the end of ovarian function and it is called 'early' or 'premature' if it occurs before 45 years. Very little is known about the menopause transition in Diabetic women. Metabolic disorders like diabetes will accelerate the reproductive ageing and determine premature ovarian failure by various mechanisms. Early menopause along with diabetes has a synergistic effect over the incidence of cardiovascular diseases and other illnesses. There is no data regarding menopausal age in Indian population. Hence, present study was aimed at understanding the age of menopause in diabetic Indian women. MATERIALS AND METHODS: This study was carried out at a tertiary care, teaching hospital in Southern India. Post-menopausal women who attended the Department of Medicine during August 2013 to August 2014, were included in the study. Six hundred patients were recruited by a systematic random sampling, 300 diabetic and 300 non-diabetic after obtaining their consents. They were all non-smokers, took mixed diet and other somatometric variables were similar in both the groups. RESULTS: Average age of menopause among diabetic women was 44.65 years which is much earlier than the menopause in non-diabetic women (48.2 years). Out of the 600 women, 212 women had an early menopause (<45 yrs.). Among them, 54 were non diabetic and 158 were diabetic. Present study also revealed a higher BMI among the diabetics than the non-diabetic women. This may be due to the changes in body composition and increase in abdominal fat after menopause. This change is more in diabetics due to the disturbances in insulin sensitivity and glucose metabolism. CONCLUSION: The present study confirms that Type 2 Diabetes increases the risk of early menopause. The study reinforces the importance of early diagnosis and treatment of diabetes for a long term well being of a woman. PMID- 26557556 TI - Prevalence and Spectrum of Gastro Esophageal Reflux Disease in Bronchial Asthma. AB - BACKGROUND: There exists a complex interplay between asthma and gastroesophageal reflux disease. Both these diseases are known to aggravate each other and amelioration of one is necessary for the control of the other. There is a paucity of studies in Indian population on this subject. AIM: To evaluate the clinical features and the endoscopic findings of the upper gastrointestinal tract in patients with bronchial asthma. MATERIALS AND METHODS: Study was conducted at KMC group of hospitals, Mangalore in the Department of chest medicine in association with Department of gastroenterology. Subjects included 50 cases of bronchial asthma and controls were 58 non asthmatic patients with allergic rhinitis and chronic urticaria. All patients were queried about presence or absence of symptoms of upper gastro intestinal tract disorders by gastro oesophageal reflux disease (GERD) questionnaire and all the included patients underwent upper gastro intestinal endoscopy. RESULTS: The study showed that symptoms of gastroesophageal reflux were significantly more in asthmatics (52%) as compared to the controls (28%). The common presenting features of gastroesophageal reflux in asthmatics were heartburn (40%) retrosternal pain (24%), nocturnal cough (18%), dyspepsia (16%) and regurgitation (14%) and the above symptoms were significantly more common in asthmatics as compared to controls. Gastroesophageal reflux disease was found to be significantly more common in the asthmatics (58%) as compared to the control group where it was present in 32.75% of the subjects. Clinical or endoscopic evidence of any upper gastrointestinal disorder was found in 68% of the asthmatics as compared to 37.93% of the controls. This difference was found to be statistically significant. CONCLUSION: The study showed that gastroesophageal reflux disease was significantly more in asthmatics as compared to the controls. Upper gastrointestinal symptoms were more common in asthmatics as against controls. Clinical or endoscopic evidence of upper gastrointestinal disorder and gastroesophageal reflux disease was found in significantly higher proportion of the asthmatics as compared to the controls. Clinically silent gastroesophageal reflux disease was however seen in both control and asthmatic groups equally with a lower prevalence. PMID- 26557558 TI - Primary Antiphospholipid Antibody Syndrome: A Case Report. AB - Primary Antiphospholipid antibody syndrome is a rare disease associated with thromboembolic events which may affect either the arterial or the venous vasculature. It presents with an increased risk of thrombosis in pregnant woman leading to repeated fetal losses. We present here a case of primary antiphospholipid antibody syndrome in young women who had previous event of gangrene of toes leading to their amputation and repeated fetal losses. PMID- 26557557 TI - Successful Retrieval of Uncoiled Coronary Guidewire Using Simple Balloon Method. AB - Breakage of angioplasty device in coronary artery can cause panic in the catheterization laboratory. These broken fragments may serve as a nidus for thrombus formation; hence, removal of these fragments becomes mandatory. Since the incidence of guidewire fracture during angioplasty are rarely reported, evidence-based approaches are not available for the management of such incidental conditions. Here, we report an interesting case of entrapment and unravelling of guidewire. We successfully retrieved unravelled guidewire using a noncompliant balloon inflated in the guiding catheter. Subsequently, the procedure was completed successfully with an implantation of a stent in the culprit lesion. We are of opinion that this novel technique is quite easy and less cumbersome than other described techniques reported earlier. PMID- 26557559 TI - Innominate Artery Aneurysm: Simulating a Thyroid Nodule. PMID- 26557560 TI - Pancreatic Lipomatosis: Complete Replacement of Pancreas by Fat. PMID- 26557561 TI - Clinical and Haematological Effects of Hydroxyurea in beta-Thalassemia Intermedia Patients. AB - INTRODUCTION: It is well known that hydroxyurea (HU) impacts on clinical and haematologic indices in thalassemia. We aimed to evaluate the effect of hydroxyurea on clinical and haematological improvement in children with thalassemia intermedia. MATERIALS AND METHODS: After the patients' enrollment in the study their data such as transfusion, hospitalization, spleen size, visit, total Hb, HbF levels, MCV and MCH were compared before and after treatment with HU 10 mg/kg/day/for one year. RESULTS: In patients with thalassemia intermedia, HU significantly diminished the rate of transfusion, hospitalization, spleen size and significantly increased Hb MCH, HbF and MCV. Moreover HU was well tolerated in our patients and we got no remarkable adverse effect. CONCLUSION: We divulged hydroxyurea 10 mg/kg/day during one year. This significantly increased HbF, total haemoglobin, MCV, MCH, without any remarkable adverse events. PMID- 26557562 TI - Is Prophylactic Drainage of Peritoneal Cavity after Gut Surgery Necessary?: A Non Randomized Comparative Study from a Teaching Hospital. AB - INTRODUCTION: Prophylactic use of intra-peritoneal drain is commonly practiced by surgeons in the hope of early detection of complication and reducing mortality and morbidity. The aim of the study was to determine evidence based value of prophylactic drainage of peritoneal cavity in cases of secondary peritonitis and resection and anastomosis of small and large bowel. MATERIALS AND METHODS: One hundred and seventy one (171) cases were included in the study from March 2012 May 2013 that underwent laparotomy for peptic ulcer perforation (PUP), simple and complicated acute appendicitis (appendicular perforation with localized/generalized peritonitis), small bowel obstruction (SBO) and sigmoid volvulus, traumatic and non-traumatic perforation of small and large bowel. Appropriate management was done after resuscitation and investigation. After completion of operation peritoneal cavity was either drained or not drained according operator's preference. They were divided into drain and non-drain groups. Surgical outcome and postoperative complications <=30 days of operation was noted and compared between two groups. RESULTS: No significant difference was observed between drained group and non-drained group in terms of age (32.08+/ 15.99 vs. 35.57 +/- 16.42 years), Sex (76M: 42F vs. 40M: 13F), weight 50.9 +/- 11.75 vs. 48.4 +/- 16.1 kg), height (1.6 +/- 0.13 vs. 1.5 +/- 0.18 Meter), BMI (20 +/- 4.7 vs. 20 +/- 7.2), ASA score (p= >0.05). However there was significant difference was observed between drained group and non-drained groups in terms of length of hospital stay (9 +/- 4 vs 5 +/- 3.4 days), operative duration (115.6 +/ 41.0 vs. 80 +/- 38.1 minutes), infection rates in dirty wound (40.0% vs 12.5%) and overall postoperative complications (35.85% vs16.11%). CONCLUSION: Based on these results, present study suggests that prophylactic drainage of peritoneal cavity after gastrointestinal surgery is not necessary as it does not offer additional benefits for the patients undergoing gut surgery. Moreover, it increases operative duration, length of hospital stay and surgical site infection (SSI). PMID- 26557563 TI - Missed Iatrogenic Bladder Rupture Following Normal Vaginal Delivery. AB - Bladder rupture following caesarian section is well documented complications. Intraperitoneal bladder rupture following normal vaginal delivery is very rare. Hereby, we present a case report of intraperitoneal bladder rupture presented late following normal vaginal delivery. We report a case of spontaneous intraperitoneal urinary bladder rupture following uneventful outlet forceps delivery in a 22-year-old primi gravid woman with gestational diabetes mellitus and fetal macrosomia who presented with large urinary ascites, anuria and renal failure. Emergent exploratory laparotomy with repair of the intraperitoneal bladder rupture helped to prevent its potential complications. Postpartum patients who undergo episiotomy or perineal repair may land up in unnoticed urinary retention which may rarely terminate in spontaneous urinary bladder rupture. Awareness of its manifestations amongst emergency physician would help to initiate appropriate timely management. PMID- 26557564 TI - Giant Gastric Lipoma Presenting as Gastric Outlet Obstruction - A Case Report. AB - Gartric lipomas are rare. They are mostly small in size, and usually remain asymptomatic. We report a case of giant (14*11cm) gastric lipoma in a 46-year-old male who presented with features of gastric outlet obstruction clinically mimicking gastric malignancy. Upper endoscopy showed a large smooth polypoid mass with broad base arising from posterior wall of gastric antrum with areas of superficial ulcerations. Multiple endoscopic biopsy specimens were nondiagnostic. A computed tomography (CT) scan of the abdomen revealed a huge cauliflower- like intraluminal mass with lobulated surface projecting into gastric lumen and pyloric canal. The mass demonstrated uniform fat density consistent with lipoma. The case is presented to stress the diagnostic problems related to this condition, and emphasize the role of CT in arriving at a correct diagnosis of lipomatous gastrointestinal tract tumours. PMID- 26557565 TI - Gas in Hepatic Portal Veins with Gastric Massive Dilatation and Pneumatosis in Acute Pancreatitis. AB - Gas in portal veins is a rare phenomenon observed secondary to bowel ischaemia and necrosis. A young girl with history of pica ingestion presented with acute abdomen with huge distension. Investigation revealed air in hepatic portal veins, air within stomach wall, and massive distension of stomach secondary to acute pancreatitis. Successful conservative treatment confirmed the current concept that all cases of hepatic portal venous gas do not warrant immediate surgical intervention. PMID- 26557566 TI - Schwanomma From Cervical Sympathetic Chain Ganglion - A Rare Presentation. AB - Schwanommas arising from cervical sympathetic chain are tumours that are rare in occurrence. These lesions are usually difficult to differentiate from a vagal schwanomma and a carotid body tumour during the initial workup. In this report, a rarely seen huge cervical sympathetic chain schwanomma case with partial Horner's syndrome is being presented in detail, which to our known knowledge, is one of the few cases reported in literature. PMID- 26557567 TI - Primary Retroperitoneal Inflammatory Myofibroblastic Tumour. PMID- 26557568 TI - Risk Factors for Stress During Antenatal Period Among Pregnant Women in Tertiary Care Hospital of Southern India. AB - BACKGROUND: The well-being of an infant may be affected when the mother is subjected to psychosocial stress during her pregnancy. Mothers exposed to stressful conditions were more prone for preterm birth than those without any stress. In this study perceived stress has been used as an indicator of levels of stress. There are very few studies published from developing countries on the levels of perceived stress and its causes in pregnant women. MATERIALS AND METHODS: This study employed a cross-sectional assessment of pregnant women attending the outpatient services of a tertiary care hospital for regular antenatal check-up. Women not known to have any risk factors at 28 weeks to 34 weeks of pregnancy who agreed to participate in the study were interviewed to assess the perceived stress score. RESULTS: Among the total patients 57.7% were primigravida and the mean score on perceived stress scale was 13.5+/-5.02. The majority of the group (102; 65.4%) scored higher than the mean value of total score on the perceived stress scale. Unplanned pregnancy and husband's employment status were associated with high levels of perceived stress in multivariate analysis in this set of women. CONCLUSION: Individual as well as pregnancy related factors can contribute to perceived stress in pregnant women. With the established relationship between maternal mental health, pregnancy outcome and infant growth, the assessment and management of stress early in the pregnancy is crucial. PMID- 26557569 TI - Expectant Versus Surgical Management of Early Pregnancy Miscarriages- A Prospective Study. AB - BACKGROUND: Surgical, medical and expectant management are the various options available to manage early pregnancy miscarriages; each with its own merits and demerits. In the last two decades, the efficacy and safety of expectant management which allows for the spontaneous passage of retained products of conception has been studied and confirmed. AIM: To compare the safety and efficacy of expectant management of early pregnancy miscarriages with surgical uterine evacuation. MATERIALS AND METHODS: The prospective study conducted in tertiary care centre for 5 years, included 212 patients with USG confirmed pregnancy miscarriages of less than 13 weeks, who were allocated to expectant management (Cases, n=112) and surgical evacuation (Control, n=100). Patients were allocated for expectant management as outpatients for 2 weeks, without any intervention till they had spontaneous complete miscarriage which was confirmed by sonography. Those who failed to do so, underwent a planned surgical uterine evacuation. Emergency admission and evacuation was done, if the patients became symptomatic in the waiting period. Patients allocated to surgical group underwent planned surgical evacuation once diagnosed. Success rate and complications like emergency evacuation, vaginal bleeding, abdominal pain, limitation of physical activity and patient satisfaction were assessed. Both groups were followed up for 6 more weeks. Statistical analysis was done with Z-test. RESULTS: Success rate of the expectant management was 71% as against 97% in surgical group. Severe vaginal bleeding was comparable (5% in both groups), 8% of expectant had severe abdominal pain versus 4% in surgical group. Unplanned admissions and emergency evacuation rate was high in expectant 9% against 1% in surgical group. Twenty one percent patients in expectant and 17% patients in surgical group experienced limitation of physical activity. Overall patient satisfaction rate was comparable (74% in expectant 80% in surgical group). CONCLUSION: Expectant management of miscarriages has a success rate of 71%. Compared to surgical management, abdominal pain, unplanned admissions, emergency evacuation and limitation of physical activity were more in expectant group. Success rate can be improved and complications can be minimised with proper patient selection and counseling. PMID- 26557570 TI - Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia. AB - INTRODUCTION: Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. MATERIALS AND METHODS: Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient's age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. RESULTS: Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were evaluated as stage 3C. CONCLUSION: The risk of endometrial cancer in patients diagnosed with endometrial hyperplasia especially endometrial hyperplasia ranges between 15% to 45% and among them 7.9% 51% are found to have myometrial inversion. Therefore, preoperative ultrasound and magnetic resonance imaging should be perfomed in patients diagnosed with complex atypical hyperplasia. Even intraoperative frozen section examination can provide useful information in selected cases. PMID- 26557572 TI - A Rare Case of Bilateral Broad Ligament Haematoma in Twin Pregnancy. AB - We report a rare case of bilateral broad ligament haematoma in twin pregnancy presented as gravida 3 para 2 living 2 (G3P2A0L2), with undelivered second twin with transverse lie with cord and hand prolapse with obstructed labour referred to our hospital from primary health centre after spontaneous vaginal delivery of first live healthy twin baby four hours later. On examination patient was stable, her investigations were within normal limits and patient was taken up for emergency lower segment caesarian section. Intraoperatively features of obstructed labour were present; a dead term baby was extracted with dichorionic diamniotic placenta. Bilateral broad ligament haematomas approximately of 8x8 cm were noted which were increasing in size after extraction of baby. On both sides haematomas were evacuated and drained along with bilateral uterine artery ligation. Three pints of blood were transfused intra and postoperatively. Her postoperative period was uneventful and the patient was discharged on postoperative day 14. PMID- 26557571 TI - Uncommon Presentation of Triploidy: A Case Report. AB - A 28-year-old woman presented in her first pregnancy was admitted with severe hyperemesis gravidarium. Increased nuchal translucency with cardiac anomaly and omphalocele at the first trimester was observed at the ultrasound examination. Chorionic villus biopsy confirmed triploidy. The combination of type I and type II triploidy patterns were seen together in the second trimester of the pregnancy. Although the symptoms due to increased human chorionic levels occured, at the pathologic investigation there were no molar changes in the placenta. Here we report a case of uncommon presentation of triploidy. PMID- 26557573 TI - Large Nabothian Cyst Obstructing Labour Passage. AB - Nabothian cysts are common and silent retention cysts of the uterine cervix with no particular intervention required. It is quite rare to reach a size of more than 4 cm and it is a diagnostic dilemma to differ it from adenoma malignum. We report a case of a woman with 38 weeks of gestation presented to the maternity unit with labour pain and protruding cystic mass (60x70 mm) out of the vagina. Simple drainage was performed to allow the vaginal delivery. She delivered 4130 grams, 9-10 Apgar, male baby by spontaneous vaginal delivery. The patient's and the newborn postpartum course was uneventful. Gynaecologic examination revealed a persisting cystic mass in the cervix (40x50 mm) two months after the delivery. We performed a total excision of the cyst to confirm the pathologic diagnosis. This paper is the first report of nabothian cysts obstructing labour passage. In the view of this case, we aimed to discuss cervical cystic masses and a review of the literature. PMID- 26557574 TI - Urethral Diverticulum Masquerading as Anterior Vaginal Wall Cyst: A Diagnostic Dilemma. AB - Urethral diverticulum (UD) is a condition in which a variably sized outpouching forms, next to the urethra. Because it connects to the urethra, this outpouching repeatedly gets filled with urine during micturition, thus causing symptoms. In females, it presents as a bulge in anterior vagina, mimicking a vaginal wall cyst. Various aetiologies proposed attributing to urethral diverticulum formation is repeated infection of the periurethral gland, childbirth trauma, iatrogenic and urethral instrumentation. Patients of UD present with non specific irritative lower urinary tract symptoms such as increased frequency, urgency and dysuria; symptoms may not correlate with the size of the diverticulum. Recurrent cystitis or urinary tract infection is seen in one-third of patients. Pain, hematuria, post-void dribbling, dyspareunia, urinary retention or incontinence is other symptoms. In some cases, there may be associated urethral calculi or carcinoma. Magnetic resonance imaging (MRI) is highly sensitive and specific for the diagnosis of UD, although non invasive sonography may be the first line investigation. Treatment is by transvaginal diverticulectomy or marsupialization. A 60-year-old P9L6 postmenopausal lady, presented with a tender, hard suburethral anterior vaginal wall mass. Cystourethroscopy revealed a small opening in posterior urethra, with stone visible through it. With the final diagnosis of suburethral diverticulum with retained multiple calculi, excision of the diverticulum and repair of urethra was done vaginally. Correct evaluation and treatment of this condition can lead to avoidance of urinary tract injury. PMID- 26557575 TI - Appendicitis in Postpartum Period: A Diagnostic Challenge. AB - Infections that occur in the postpartum period are assumed to be related to pregnancy or delivery; however other causes should also be considered. Appendicitis is one of the most common conditions requiring laparotomy during pregnancy, but very few cases of postpartum appendicitis have been reported. We report two such cases and the challenges faced by clinicians in diagnosis of immediate postpartum appendicitis. The first case was managed on lines of puerperal sepsis and the second one as enteric fever. Appendicular pathology was detected incidentally on laparotomy. In postpartum patients with no obvious focus of sepsis, appendicitis should be kept in mind. A team approach involving sensitized obstetricians and surgeons is likely to reduce serious morbidities. PMID- 26557576 TI - Fibroepithelial Polyps of the Vagina in Pregnancy. PMID- 26557577 TI - Case series: Pregnancy Outcome in Patients with Uterine Fibroids. AB - Fibroids in pregnancy is a commonly encountered clinical entity. Objective of this study was to evaluate the maternal and fetal outcome in women having pregnancy with uterine fibroids. We present the clinical, obstetric data, perinatal outcomes of 15 patients from a prospective study. Fifteen pregnant women with fibroid >3cm were prospectively included in study. Major proportion of patient with fibroids were in younger age group of 25-30 years when compared to older age group of 31-35 years (66% vs 33%). Fibroids were more frequent in multi gravidae, compared to primigravidae. In almost half of patients, (53.3%) fibroids were diagnosed before pregnancy. Common complications encountered during pregnancy in decreasing order of frequency were pain abdomen (46.6%), followed by threatened preterm labour (26.6%) and anaemia (26.6%). Out of 15, three (20%) women had abortion. In remaining, 11/12 patients attained term pregnancy between 37 to 40 weeks. Two patients required antenatal myomectomy. Caesarean section was done in 75% of women who attained term pregnancy and one patient had technical difficulty during caesarean section. Post partum heamorrhage was seen in 5/15 (33.3%) of patients. Out of 12, five babies were low birth weight. Four babies required NICU admission. There was no perinatal mortality. In our small patient series high incidence of caesarean section rates and increased incidence of threatened preterm labour, anaemia, and postpartum haemorrhage, was observed in pregnant patients with fibroids and hence, the pregnancy with fibroids should be considered as high risk pregnancy. PMID- 26557578 TI - Diagnosis and Treatment of Symptomatic Carpal Bossing. AB - CONTEXT: Carpal bossing is an osseous formation at the dorsal portion of the quadrangular joint, which rarely becomes symptomatic. However, in some patients it causes pain, restricted mobility and can lead to complications like tendon rupture, inflammatory and degenerative joint disease. AIM: In this article, we present our experiences with this rare disorder in order to improve diagnostic and therapeutic proceedings. SETTINGS DESIGN: This is a multicenter and interdisciplinary observation made by orthopaedic surgeons and radiologists in the years 2010 to 2015. Retrospective observational study. The follow up period was 2 years. MATERIALS AND METHODS: In the observed time period, eight patients were diagnosed with symptomatic carpal bossing. Symptoms were pain at palmar flexion and limited mobility of the wrist in combination with a palpable protuberance over the quadrangular joint. All patients underwent X-ray, CT and MRI examinations. A conservative treatment strategy was initiated for 6 weeks in all patients, followed by a wedge resection when symptoms were persisting and disabling. RESULTS: After the conservative treatment schedule, five patients were asymptomatic. Three patients had persisting pain and were thus recommended for surgery. In the postoperative course, two patients were asymptomatic. One patient developed a type 1 complex regional pain syndrome (CRPS) in the first postoperative year, which was successfully treated with pain-adapted physiotherapy, pharmacotherapy with analgesics and calcitonin, and a triple CT guided thoracic sympathetic nerve blockade. CONCLUSION: Carpal bossing is a mostly asymptomatic entity, which in our experience gets symptomatic due to direct trauma or repetitive stress, especially in competitive racket sports players. It can be diagnosed by thorough clinical examination and multimodal diagnostic imaging. Conservative treatment comprises an excellent prognosis, however surgery, either wedge resection or arthrodesis, must be considered if the response is not positive after 6 weeks. PMID- 26557579 TI - Current Clinical Practice Scenario of Osteoporosis Management in India. AB - BACKGROUND: Various osteoporosis guidelines are available for practice. AIM: To understand the current clinical practice scenario from the perspective of Indian orthopaedicians, especially about the epidemiology, clinical manifestations, approach to diagnosis and management and patient compliance patterns to long term treatment. MATERIALS AND METHODS: A pre-validated structured questionnaire containing questions (mostly objective, some open-ended) catering to various objectives of the study was circulated amongst orthopaedic surgeons across India by means of post/courier, after giving a brief overview of the study telephonically. Data was extracted from the completed questionnaires, and analysed using Microsoft Excel software. RESULTS: The questionnaire was filled by a total of 84 orthopaedicians throughout India. The prevalence of osteoporosis in India according to the orthopaedic surgeons was 38.4% and there was a female preponderance. Most of the respondents felt out of every 100 osteoporosis patients in India, less than 20 patients are actually diagnosed and treated for osteoporosis. The most common initial presenting feature of established osteoporosis cases was general symptoms. Most respondents preferred Dual-energy X ray absorptiometry (DEXA) as the initial investigation for the diagnosis of osteoporosis in a patient presenting with typical features. While most respondents preferred once-a-month oral over intravenous (IV) bisphosphonates, they agreed that IV administration had advantages such as lower gastrointestinal side effects and improved compliance. The average duration of therapy of oral bisphosphonates was the longest (27.04 months) among the other anti- osteoporosis therapies that they used. On an average, the patient compliance rate in osteoporosis management was around 64%. IV Zoledronic acid (ZA) and intranasal calcitonin were infrequently used than other anti- osteoporosis therapies. While concerns about cost and availability deterred more frequent usage, there was an agreement that if used regularly these two agents may improve compliance rates among patients. CONCLUSION: Current clinical practice scenario of osteoporosis management in India largely adheres to various clinical practice guidelines for osteoporosis. Side effects and lengthy duration of therapy with bisphosphonates seem to be the main factors leading to a low patient compliance. Widespread popularization of once-yearly Zoledronic acid and intranasal calcitonin spray may improve patient compliance and reduce side effect incidence. PMID- 26557580 TI - Management of Osteoarthritis Knee by Graduated Open Wedge High Tibial Osteotomy in 40-60 Years Age Group Using Limb Reconstruction System: A Clinical Study. AB - BACKGROUND: With i ncrease in elderly population, osteoarthritis has become major concern nowadays. Knee joint is most commonly affected joint. A number of methods have been developed in the last few years which help in treating the osteoarthritis knee, which includes non pharmacological, pharmacological and surgical methods. Among the most promising techniques with renewed interest for osteoarthritis knee with deformity is the use of high tibial osteotomy. Uni compartmental osteoarthritis knee with deformity especially in relatively younger age group (less than 60 years) constitutes the main indication. AIM: The aim of present study was to evaluate management of osteoarthritis knee by graduated open wedge high tibial osteotomy in 40-60 years age group using limb reconstruction system. MATERIALS AND METHODS: Medial Opening Wedge High Tibial Osteotomy leaving the lateral cortex intact which acts as a hinge, was done in 30 patients and stabilized by Limb Reconstruction System. Distraction was started at 7(th) day at the rate of 1 mm/day and continued till proper alignment was achieved. RESULTS: Medial Opening Wedge High Tibial Osteotomy stabilized by unilateral external fixator is a good method for unicompartmental osteoarthritis knee with deformity as it gives precise control over final limb alignment and its ability to perform a residual correction. Deformity correction can be quantified at the time of correction as it is not acute correction. Gradual deformity correction can be done over time by distraction histogenesis with the help of unilateral external fixator. It is also a good method in young patients requiring large correction. CONCLUSION: Medial Opening Wedge High Tibial Osteotomy is having many benefits over closed wedge osteotomy and stabilization by unilateral external fixator also has its added benefits. It is less invasive, no internal hardware present and safer in terms of neurovascular complications. PMID- 26557581 TI - Claudication Due to Sciatic Nerve Palsy Following Nicolau Syndrome: A Case Report. AB - Nicolau syndrome is a rare drug reaction due to intramuscular injection administration that can lead to limb loss or even death. A 3.8-year-old Iranian boy received an intramuscular injection of Benzathine Penicillin. Immediately after injection the child developed lower limb pain and livedoid discolouration and was referred to our department. The patient was diagnosed to develop Nicolau syndrome and fasciotomy carried out due to compartment syndrome. Pharmacologic therapy with Heparin, Cefazolin and Methylprednisolone was initiated. On 18(th) day, he was discharged, although he was not able to move. Finally, after 6 months of care at home, physiotherapy and Electromyography (EMG) at regular intervals, the child was gradually able to move and his claudication improved. PMID- 26557582 TI - A Rare Case Report on Bilateral Intertrochanteric Fractures in a Child Following Child Abuse. AB - Diagnosis of non accidental injury needs careful history elicitation, proper examination and thorough workup including blood investigation and radiological assessment to avoid misdiagnosis or under diagnosis. Correct diagnosis and reporting would avoid possible similar incidents in the future. Four-year-old female child brought to our hospital by her mother with apparent history of fall from height. Following detailed examination and radiological assessment we suspected of child abuse. Child had multiple fractures in different stages of healing which included bilateral intertrochanteric fractures. Child was operated for bilateral intertrochanteric fractures which appeared relatively fresh compared to other old malunited fractures with open reduction and fixation with titanium elastic nailing and was immobilized by hip spica. Two months postoperatively, there was complete radiological union of fractures and child was being counseled by child psychologist. PMID- 26557583 TI - A Framework for Developing a Curriculum Regarding Autism Spectrum Disorders for Primary Care Providers. AB - INTRODUCTION: The prevalence of Autism Spectrum Disorders (ASDs) has increased and varies across age groups. Thus there is an increasing need for educational opportunities for General Practitioners (GPs) and other Primary Care providers to help in early identification and referral to specialist services. An earlier survey of GPs in New South Wales (Australia) demonstrated two broad domains for educational activities: (1) a general knowledge (important for early identification and referral) and (2) surveillance (important for ongoing management). AIM: To seek further evidence to these domains and synthesize the important contents for educational programs for GPs. MATERIALS AND METHODS: We conducted a (1) Confirmatory Factor Analysis (CFA) on our original survey data and (2) systematic review of the literature to identify important educational topics, using a life cycle approach. RESULTS: CFA and literature review support theoretical framework of two domains. Alerts and red flags for ASDs, knowledge of simple surveillance tools, communication of diagnosis with parents, referral pathways particularly to speech pathologists before a formal diagnosis is confirmed, and appreciation of vulnerabilities for identifying supports were important in the general knowledge domain, while supporting the families through transition points such as from pre-school to school entry, secondary school and adolescence, role of psychopharmacology such as medications for sleep issues, and for common co-morbidities of anxiety were important in the surveillance dimension. CONCLUSION: GP supervisors and medical and nursing educators can use findings from this paper for developing structured learning activities for training primary health care workforce regarding ASD's. PMID- 26557584 TI - Biological Reference Interval for Hematological Profile of Umbilical Cord Blood: A Study Conducted at A Tertiary Care Centre in South India. AB - INTRODUCTION: Umbilical cord blood (UCB) a source of hematopoietic stem cells, is also an acceptable sample to assess neonatal sepsis. Though reports are available for stem cell counts very minimal literature is available regarding hematologic parameters, which may vary on ethnicity. AIM: To establish biological reference interval for hematological parameters of umbilical cord blood to guide neonatologists, hematopoietic stem cell transplant specialists and future analysis. MATERIALS AND METHODS: Prospective longitudinal study was done from January 2014 to April 2014 after ethics committee approval. UCB from 120 full term new borns of normal birth weight born out of uneventful pregnancy to mothers aged between 21 to 45 years with hemoglobin above 10g/dL were processed in Beckman Coulter LH780 analyzer for complete blood count and counter checked by peripheral smear. Results tabulated in Microsoft excel are analyzed using IBM SPSS statistics 16 software. RESULTS: Male to female ratio is 1:1.05. There is no difference in the values between males and females. When compared with few studies available, though many values are comparable a few values are not comparable. CONCLUSION: This study can be a useful guide to neonatologists, hematopoietic stem cells transplant hematologists and future analysis. PMID- 26557585 TI - SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal Extension-II) in Predicting Mortality and Morbidity in NICU. AB - INTRODUCTION: A number of illness severity scores have evolved which would predict mortality and morbidity in intensive care units. One such scoring system developed by Richardson was SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal extension-II). AIM: The present study was conducted to assess the validity of SNAPPE-II score as a predictor of mortality and morbidity. MATERIALS AND METHODS: A total of 248 neonates who met the inclusion criteria were included in the study and SNAPPE-II score was calculated. Receiver Operating Characteristic (ROC) curve was constructed to derive the best cut-off score and SPSS package (Statistical Package for the Social Sciences) was used for statistical analysis. RESULTS: SNAPPE-II score was higher among expired neonates compared to survived ones. A mean score of 37 was associated with higher mortality. However, it didn't accurately predict the length of stay. CONCLUSION: SNAPPE II score is a better predictor of mortality irrespective of gestational ages and it is not a good predictor of morbidity. PMID- 26557586 TI - Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity. AB - Carnitine palmitoyltransferase II (CPTII) deficiency is a rare disorder of mitochondrial fatty acid oxidation with autosomal recessive mode of inheritance. Three classic forms of CPT II deficiency have been described namely the lethal neonatal form, severe infantile hepatocardiomuscular form and the myopathic form. We present a three-day-old female child, admitted to us for lethargy, icterus, low sugars and convulsions. Persistent non ketotic hypoglycaemia, hyperammonemia, raised liver enzymes with hepatomegaly and cardiomyopathy led to the suspicion of fatty acid oxidation defect. Tandem mass spectrometry helped to clinch the diagnosis of CPT II Deficiency in the present case. PMID- 26557587 TI - Acute Hypercalcaemia and Hypervitaminosis D in an Infant with Extra Pulmonary Tuberculosis. AB - In patients with tuberculosis, abnormal extrarenal production of 1,25 dihydroxyvitamin D3 by activated macrophages in granulomatous tissues may result in hypercalcaemia. More commonly reported in adults with active pulmonary tuberculosis, this complication may rarely occur in extrapulmonary tuberculosis, and children. The hypercalcaemia may be precipitated by usually recommended vitamin D and calcium supplementation in patients with tuberculosis. We report here an infant with tubercular meningitis who developed hypercalcaemia 12 days after starting routine vitamin D and calcium supplementation. This communication highlights the importance of close monitoring of calcium levels in patients with tuberculosis, especially if started on vitamin D and calcium replacement before anti-tubercular therapy. PMID- 26557588 TI - Efficacy of Transcerebellar Diameter/Abdominal Circumference Versus Head Circumference/Abdominal Circumference in Predicting Asymmetric Intrauterine Growth Retardation. AB - BACKGROUND: The high incidence of IUGR and its low recognition lead to increasing perinatal morbidity and mortality for which prediction of IUGR with timely management decisions is of paramount importance. Many studies have compared the efficacy of several gestational age independent parameters and found that TCD/AC is a better predictor of asymmetric IUGR. AIM: To compare the accuracy of transcerebellar diameter/abdominal circumference with head circumference/abdominal circumference in predicting asymmetric intrauterine growth retardation after 20 weeks of gestation. MATERIALS AND METHODS: The prospective study was conducted over a period of one year on 50 clinically suspected IUGR pregnancies who were evaluated with 3.5 MHz frequency ultrasound scanner by a single sonologist. BPD, HC, AC and FL along with TCD were measured for assessing the sonological gestational age. Two morphometric ratios- TCD/AC and HC/AC were calculated. Estimated fetal weight was calculated for all these pregnancies and its percentile was determined. STATISTICAL METHODS: The TCD/AC and HC/AC ratios were correlated with advancing gestational age to know if these were related to GA. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) for TCD/AC and HC/AC ratios in evaluating IUGR fetuses were calculated. RESULTS: In the present study, linear relation of TCD and HC in IUGR fetuses with gestation was noted. The sensitivity, specificity, PPV, NPV & DA were 88%, 93.5%, 77.1%, 96.3% & 92.4% respectively for TCD/AC ratio versus 84%, 92%, 72.4%, 95.8% & 90.4% respectively for HC/AC ratio in predicting IUGR. CONCLUSION: Both ratios were gestational age independent and can be used in detecting IUGR with good diagnostic accuracy. However, TCD/AC ratio had a better diagnostic validity and accuracy compared to HC/AC ratio in predicting asymmetric IUGR. PMID- 26557589 TI - Optic Strut and Para-clinoid Region - Assessment by Multi-detector Computed Tomography with Multiplanar and 3 Dimensional Reconstructions. AB - PURPOSE: To evaluate thickness, location and orientation of optic strut and anterior clinoid process and variations in paraclinoid region, solely based on multidetector computed tomography (MDCT) images with multiplanar (MPR) and 3 dimensional (3D) reconstructions, among Indian population. MATERIALS AND METHODS: Ninety five CT scans of head and paranasal sinuses patients were retrospectively evaluated with MPR and 3D reconstructions to assess optic strut thickness, angle and location, variations like pneumatisation, carotico-clinoid foramen and inter clinoid osseous ridge. RESULTS: Mean optic strut thickness was 3.64mm (+/-0.64), optic strut angle was 42.67 (+/-6.16) degrees. Mean width and length of anterior clinoid process were 10.65mm (+/-0.79) and 11.20mm (+/-0.95) respectively. Optic strut attachment to sphenoid body was predominantly sulcal as in 52 cases (54.74%) and was most frequently attached to anterior 2/5(th) of anterior clinoid process, seen in 93 sides (48.95%). Pneumatisation of optic strut occurred in 23 sides. Carotico-clinoid foramen was observed in 42 cases (22.11%), complete foramen in 10 cases (5.26%), incomplete foramen in 24 cases (12.63%) and contact type in 8 cases (4.21%). Inter-clinoid osseous bridge was seen unilaterally in 4 cases. CONCLUSION: The study assesses morphometric features and anatomical variations of paraclinoid region using MDCT 3D and multiplanar reconstructions in Indian population. PMID- 26557590 TI - Imaging Patterns in MRI in Recent Bone Injuries Following Negative or Inconclusive Plain Radiographs. AB - BACKGROUND: Few bony injuries and most soft tissue injuries cannot be detected on plain radiography. Magnetic resonance imaging (MRI) can detect such occult bony injuries due to signal changes in bone marrow. In addition to excluding serious bony injuries, it can also identify tendon, ligament, cartilage and other soft tissue injuries and thus help in localizing the cause of morbidity. AIMS AND OBJECTIVES: To determine the MRI imaging patterns in recent bone injuries (less than 4 weeks) following negative or inconclusive plain radiographs. To determine the role of MRI in recent fractures. RESULTS: Out of the 75 individuals with history of recent injury of less than 4 weeks duration, fracture line was demonstrated in 16 patients (21%) who had no obvious evidence of bone injury on plain radiographs. Bone contusion or bruising of the bone was demonstrated in 39 (52%) patients. This was the commonest abnormality detected in MRI. The remaining 20 patients did not show any obvious injury to the bone on MR imaging however, soft tissue injury could be demonstrated in 12 (16%) patients which show that the extent of soft tissue injury was relatively well demonstrated by MR imaging. The present study showed that occult injuries commonly occur at the Knee followed by Ankle, Wrist, Foot, Elbow, Leg, Hands, Hips & Spine. CONCLUSION: The study showed that MR is efficient in the detection of occult bone injuries which are missed on radiography. Compared to radiographs, MRI clearly depicted the extent of injuries and associated soft tissue involvement. MRI demonstrates both acute and chronic injuries and also differentiates both, whereas radiography has poor sensitivity for acute injuries. Also, the soft tissue injuries like tendionous and ligamentous injuries cannot be identified on radiographs. PMID- 26557591 TI - Comprehensive Evaluation of Cardiac Hydatid Using 256 Slice Dual Source CT: One Stop Shop. AB - Hydatid disease results from infection with larval stage of Echinococcus granulosus tapeworm. Dogs and other canines are the definitive hosts; Human beings are common accidental intermediate hosts. Liver is the most common organ to be involved in this condition. Cardiac hydatid, seen in only 0.5 to 2% cases, is a rare entity because of myocardial contractility. Larvae reach the myocardium through coronary circulation. Among various locations of cardiac hydatid, due to its rich coronary arterial supply Left ventricle (LV) myocardium is the most common site of involvement followed by interventricular septum and right ventricle. Rare locations include pericardium, right atrium and left atrium. A 50 year-old woman presented with dyspnoea for 11 months, chest X-ray showed a well defined, homogenous left paracardiac mass, which is not separable from left heart border. Transthoracic echocardiography revealed a complex multicystic mass lesion abutting antero-lateral wall of left ventricle. Contrast enhanced computed tomography showed a well-circumscribed multicystic mass lesion with honeycomb appearance arising from myocardium of anterolateral wall of left ventricle. Indirect haemagglutination test for hydatid disease was positive. At surgery the cyst was seen to arise from LV myocardium. It was incised and grape like contents were evacuated. The cavity was irrigated with scolicidal solution. Thereafter, the cyst was marsupialised. Histopathological examination revealed grape like cyst contents consistent with the diagnosis of hydatid cyst. PMID- 26557592 TI - Spermatic Cord and Peritoneal Metastases from Unruptured Hepatocellular Carcinoma. AB - Extrahepatic metastases are not uncommon in patients with late-stage hepatocellular carcinoma (HCC). These extrahepatic lesions are most commonly found in the lungs, lymph nodes and bones. The authors report the case of a patient with chronic liver disease who presented with left inguinal swelling which was thought to be incarcerated hernia on clinical examination. Further evaluation revealed that the patient had HCC with spermatic cord metastasis which was masquerading as inguinal hernia. He also had extensive peritoneal dissemination. Awareness and accurate detection of these unusual sites of extrahepatic dissemination of HCC is of paramount importance for radiologists to avoid unnecessary surgery as well as after loco regional therapy to assess for recurrence. Details of the case are discussed with a review of the relevant literature. PMID- 26557593 TI - Isolated Hypoglossal Nerve Schwannoma: An Uncommon Presentation of Schwannoma. PMID- 26557594 TI - Acute Poisonings Admitted to a Tertiary Level Intensive Care Unit in Northern India: Patient Profile and Outcomes. AB - BACKGROUND: Poisoning is becoming a real health care burden for developing countries like India. An improved knowledge of the patterns of poisonings, as well as the clinical course and outcomes of these cases can help to formulate better preventive and management strategies. AIM: To study the demographic and clinical profiles of patients admitted to the ICU with acute poisoning and to study the factors that predict their mortality. MATERIALS AND METHODS: Retrospective two years (September 1, 2010 to August 31, 2012) study of all consecutive patients admitted to the Intensive Care Unit (ICU) with acute poisoning at a tertiary care hospital in Northern India. RESULTS: Out of the 67 patients admitted to the ICU during the study period, the majority were young (median age 29 years) males (69%) who had consumed poison intentionally. Pesticides were the most commonly employed poison, notably organophosphorus compounds (22 patients, 32.8%) and aluminium phosphide (14 patients, 20.9%). While the overall mortality from all poisonings was low (18%), aluminium phosphide was highly toxic, with a mortality rate of 35%. The factors at ICU admission that were found to be associated with a significant risk of death were, high APACHE II and SOFA scores (p =0.0001 and p=0.006, respectively), as well as the need for mechanical ventilation and drugs for vasoactive support (p=0.012 and p= 0.0001, respectively). CONCLUSION: Use of pesticides for intentional poisoning continues to be rampant in Northern India, with many patients presenting in a critical condition to tertiary level hospitals. Pesticide regulations laws, educational awareness, counseling and poison information centers will help to curtail this public health problem. PMID- 26557595 TI - Psychiatric Morbidity in Patients with Chikungunya Fever: First Report from India. AB - BACKGROUND: Chikungunya fever is an acute illness caused by an arbovirus and has various complications like neurological, psychological, dermatological and even multi organ failure. Psychiatric co-morbidity is not very well studied till now. This is the first report from India. AIM: Aim of the study was to assess the psychiatric morbidity during or after the onset of Chikungunya fever. MATERIALS AND METHODS: Patients referred from Medicine department with confirmed diagnosis of Chikungunya fever were recruited, after taking informed consent. Patient's socio-demographic characteristics were noted and Psychiatric co-morbidity was assessed by complete history taking and mental status examination, using WHO International Classification of Diseases, 10(th) edition (ICD -10) of Mental and Behavioural Disorders, Diagnostic criteria for research. RESULTS: The age range of the study group was found to be 23-48 years. Fourteen (70%) were males and 6 (30%) were females. Five (25%) patients were diagnosed with depressive disorder, 3 (15%) patients had Generalized Anxiety Disorder (GAD), 2 (10%) patients GAD with Panic attacks, 1(5%) patients phobic disorder (claustrophobia), 3 (15%) patients Somatoform Disorder, 3 (15%), Neurasthenia (Fatigue Syndrome), etc. Two (10%) patients presented with vague somatic complaints which did not fit into any of the diagnostic category. CONCLUSION: Chikungunya fever can result in significant psychiatric morbidity, mainly in the form of depressive episode, anxiety disorder and even long persisting illnesses like somato-form disorders. Further research is required to know about the phenomenology or the neurobiology of the psychiatric disorders occurring in the course of this illness. PMID- 26557596 TI - Personality Factor as a Predictor of Depression Score Among Depressed and CHD Patients. AB - INTRODUCTION: Many risk factors can affect depression and coronary disease, these including physiological and psychological risk factors (such as personality traits). OBJECTIVES: Our objectives were to examine whether personality factors (The Five-Factor Model) can predict depression score in the depressed and coronary heart disease (CHD) individuals compared to that of healthy subjects. MATERIALS AND METHODS: To achieve the above objectives, 100 depressed (Mean=35.90 years, SD=10.59 years), and 100 CHD (Mean=46.42 years, SD=12.52 years), patients and 100 healthy subjects (Mean = 37.97 years, SD =12.49 years) were selected by convenience sampling method. To compare the three groups of participants, ANOVA test was used. Stepwise Multiple Regression Analysis was used to identify the variables that most closely predict the perceived stress and depression scores. Pearson's Correlation Co-efficient was used to examine the correlation between variables. RESULTS: In Neuroticism, the CHD patients had significant highest scores, followed by depressed patients. The healthy group had the least scores. In case of Extraversion, Openness and Agreeableness, healthy participants had significant higher scores followed by the depressed and CHD patients. Only in conscientiousness factor, Depressive and CHD groups had statistically less scores compared to the healthy group. Also, high Neuroticism and Age, and low Extraversion were significant protective factors for depression Scores of CHD patients, while high Neuroticism and low Extraversion function as predictors in the depressed and healthy groups. CONCLUSION: The effects of Neuroticism and Extraversion on depression have been reported as inconsistent across previous studies. This study indicates that, older CHD individuals with high Neuroticism and low Extraversion scores are more vulnerable for depression. PMID- 26557597 TI - Quality of Life Perspective Towards Acne among Adolescents at Tertiary Care Center of Gujarat, India. AB - INTRODUCTION: Acne is the most common disease of skin affecting adolescents, which can have a significant psychological impact leading to anxiety and depression. AIMS: Study was undertaken to see the impact of acne on the Quality of life. MATERIALS AND METHODS: The study was conducted from March 2012 to February 2013, in the age group 14-25, using a validated self-administered questionnaire The questions were evaluated using 4 point Likert scale (0-3). STATISTICAL ANALYSIS: Statistical calculations were done using Excel 2010 and Statgraphics Centurion XVI.I. RESULTS: Among 869 participants, 608(69.97%) had acne while 261 (30.03%) had no acne. Of acne sufferers 43.75% were males and 56.25% were females with maximum 67.93% in the age group 18-21. Of Non-acne participants 57.09% considered acne as a problem and 54.02% were disturbed by the idea of having acne. Study showed p-values<0.05 indicating statistically significant non-zero correlations at 95.0% confidence level. CONCLUSION: The quality of life scale of acne varies according to individual perception and differs from population to population. Questionnaire evaluation is a useful tool, but cannot replace proper psychological assessment. PMID- 26557598 TI - Pseudoepitheliomatous, Keratotic and Micaceous Balanitis: A Case Report. AB - Pseudoepitheliomatous, keratotic and micaceous balanitis (KPMB) is a rare condition affecting glans penis of elderly men. It is characterized by thick hyperkeratotic plaque with micaceous scaling often leading to phimosis. Here we are reporting a rare case of pseudoepitheliomatous, keratotic, and micaceous balanitis in 50-year-old man who has undergone circumcision 16 years back. Till date only a handful cases have been reported in world literature. PMID- 26557599 TI - Impact of Induction Chemotherapy Followed by Radiotherapy in Patients of Invasive Cervical Carcinoma with Inadvertent Hysterectomy: A Retrospective Study. AB - BACKGROUND: The standard of care for patients who undergo an inadvertent hysterectomy for invasive cervical carcinoma is not well established. AIM: The aim of this study was to evaluate the role of induction chemotherapy followed by external beam radiotherapy and brachytherapy in patients who had an inadequate hysterectomy for carcinoma of the cervix. MATERIALS AND METHODS: Patients with history of inadequate hysterectomy with no residual disease at presentation to our outpatients department of Radiotherapy and registered between October 2011 to June 2014 were retrospectively analyzed. Most of these patients had received three cycles of induction chemotherapy using Paclitaxel and Carboplatin regime. Thereafter, these patients had received external beam radiotherapy and vaginal brachytherapy. The primary end points were overall survival and disease-free survival. Survival analysis was done using Kaplan-Meier method and the differences in survival rates were compared using log-rank test. RESULTS: A total of 34 patients were eligible for the study. Overall survival and Disease-free survival at 3-years were 70% and 68%. Patients who had Taxane-based chemotherapy had significantly better survival outcomes than their counterparts. Vaginal vault boost with brachytherapy had a significant impact on prognosis of these patients. CONCLUSION: Induction chemotherapy using Paclitaxel and Carboplatin followed by external beam radiotherapy and brachytherapy is a good treatment option for patients of carcinoma of the cervix who have undergone inadvertent hysterectomy. PMID- 26557600 TI - Adjuvant Radiotherapy with Three-Dimensional Conformal Radiotherapy of Lacrimal Gland Adenoid Cystic Carcinoma. AB - BACKGROUND & AIM: Adenoid cystic carcinoma (ACC) of lacrimal gland is a rare tumour with aggressive behaviour. There is sparse data to address optimum therapy for such tumours. So, the present study was aimed at evaluating the role of adjuvant three dimensional conformal radiotherapy (3D-CRT) in cases of incomplete (R1) resection along with review of literature pertaining to management of lacrimal adenoid cystic carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the demographic and treatment data of 10 biopsy proven ACC of lacrimal gland patients, treated from December 2006 to June 2013. They were treated with radiotherapy following surgical resection. Eight patients underwent gross total excision of the tumour mass (enbloc excision) followed by conformal radiotherapy to a dose of 60 Gray/30fractions/ 6 weeks. Two patients with advanced disease were treated with palliative radiotherapy after biopsy. RESULTS: The median age was 32 years. There were equal numbers of male and female patients. The median duration of symptoms was 7 months. At a median follow up of 21 months, eight patients had no evidence of disease and had complete tumour response, two patients worsened, and one of the two had systemic failure with bone metastasis. CONCLUSION: Despite a small sample size and short follow, enbloc surgical excision with adjuvant radiotherapy is well tolerated and shows good control in ACC of lacrimal gland. PMID- 26557601 TI - Induction Chemotherapy with Cisplatin and 5-Fluorouracil in Advanced Head and Neck Cancers: A Short Term Response Evaluation. AB - BACKGROUND: Considering the uprising number of Head and neck cancer in the state with limited options of medical and surgical treatment, the focus of this study involved on chemotherapy in advanced Head and neck cancers. The aim of this study was to evaluate the efficacy and toxicity of combination of Cisplatin and 5 Fluorouracil (PF) as induction chemotherapy in patients in locally advanced squamous cell cancer of head and neck. MATERIALS AND METHODS: Forty four patients with previously untreated stage III -IV advanced and inoperable cases were included in this prospective study. Induction chemotherapy consisted of 3 cycles of Cisplatin 100mg/mt(2) as infusion on day 1, 5-Fluorouracil of 750mg/mt(2) on day 2, 5-Fluorouracil of 1000mg/mt2 as infusion on day 3 in an inpatient basis. Cycles were repeated with an interval of 21 days. Patients were evaluated within a period of 3 weeks at the end of completion of third cycle of chemotherapy. Post chemotherapy local therapy was individualized based on the response, site and stage of the tumour. RESULTS: Out of 44 eligible and evaluable patients, major dominance was noted in male group constituting 68%. After induction chemotherapy 58.8% of stage III experienced stable response, & 44% had partial response. In stage IV, 44% showed a stable response and 33.3% had partial response. But in comparison to primary tumour response and nodal response, which had a significant clinical response, the overall response of malignancy with respect to stage and site specificity was clinically insignificant. Moderate adverse reaction was noted in 47.6% and 42.1% had mild reactions. Majority of patients experienced grade 3 adverse events, of which anaemia in females and leucopenia in males pre dominated. CONCLUSION: With the use of cisplatin and 5-FU as induction chemotherapy agents in advanced and inoperable squamous cell carcinoma of head and neck, a distinct benefit was seen in stabilizing the tumour from progression. But achieving a significant complete response to the same is of faint possibility. An alternate multidrug regimen or multimodality treatment would be ideal to gain the optimum results from induction agents. Toxicity related to chemotherapy usually is transient at therapeutic doses, and can be controlled by adequate prophylactic measures. PMID- 26557602 TI - Low Grade Fibromyxoid Sarcoma of the Palate: A Case Report. AB - Low-grade fibromyxoid sarcoma (LGFMS) are rare soft-tissue sarcomas that usually come to attention as slow growing masses. Males and females are affected approximately equally and typically arising in the soft tissue of the proximal extremities. Primary occurrence within the head and neck is exceedingly rare. We report a case arising from the hard palate of a 40-year-old male and according to our knowledge this is the first ever case of LGFMS involving the palate to be reported. PMID- 26557603 TI - Validation of Gujarati Version of ABILOCO-Kids Questionnaire. AB - BACKGROUND: ABILOCO-Kids is a measure of locomotion ability for children with cerebral palsy (CP) aged 6 to 15 years & is available in English & French. AIM: To validate the Gujarati version of ABILOCO-Kids questionnaire to be used in clinical research on Gujarati population. MATERIALS AND METHODS: ABILOCO-Kids questionnaire was translated into Gujarati from English using forward-backward forward method. To ensure face & content validity of Gujarati version using group consensus method, each item was examined by group of experts having mean experience of 24.62 years in field of paediatric and paediatric physiotherapy. Each item was analysed for content, meaning, wording, format, ease of administration & scoring. Each item was scored by expert group as either accepted, rejected or accepted with modification. Procedure was continued until 80% of consensus for all items. Concurrent validity was examined on 55 children with Cerebral Palsy (6-15 years) of all Gross Motor Functional Classification System (GMFCS) level & all clinical types by correlating score of ABILOCO-Kids with Gross Motor Functional Measure & GMFCS. RESULT: In phase 1 of validation, 16 items were accepted as it is; 22 items accepted with modification & 3 items went for phase 2 validation. For concurrent validity, highly significant positive correlation was found between score of ABILOCO-Kids & total GMFM (r=0.713, p<0.005) & highly significant negative correlation with GMFCS (r= -0.778, p<0.005). CONCLUSION: Gujarati translated version of ABILOCO-Kids questionnaire has good face & content validity as well as concurrent validity which can be used to measure caregiver reported locomotion ability in children with CP. PMID- 26557604 TI - The Use of the MyoDK for Mechanical Pressure in the Treatment of Chronic Lateral Epicondylalgia: A Pilot Study. AB - INTRODUCTION: Chronic Lateral Epicondylalgia (CLE) is potentially associated with a significant reduction of the patient's quality of life; its treatment by manual Deep Transverse Friction (DTF), although widely accepted, lacks standardization. The purpose of our study was to evaluate the efficacy of the MyoDK device, which allows deep transverse pressure (DTP) monitoring, for treatment of CLE. MATERIALS AND METHODS: This is a single centre observational study for treatment of CLE by the MyoDK device. In a given year, all patients who appeared at our institution with a diagnostic of CLE were screened for possible inclusion. Exclusion criteria were: confounding factors on pain and function of the upper limb, cognitive impairment, inability or unwilling to give informed consent or to comply with treatment protocol. Our primary outcome measure was the pain reduction measured by the VAS pain scale (VAS) at 6 weeks. Our intervention consisted in applying a pressure from 0.5 to 10kg/100mm(2) for 20 minutes, once a week for 6 weeks, using the MyoDK device. RESULTS: Thirty patients were screened. Two were excluded for incomplete protocol, remaining 28 for analysis. Mean age was 47.3, 23 were male (82.1%), 24 were affected on their dominant side (85.7%). We had a significant reduction in VAS pain score at 12 weeks (80.8 vs 13.0; p<0.01). There were no side effects reported. CONCLUSION: Our study showed the safety of the use of a standard protocol using the MyoDK device for treatment of CLE. We believe that further controlled studies will establish the MyoDK as a reliable option for treatment of CLE. PMID- 26557605 TI - Effect of Surgical Periodontal Therapy on Serum C-reactive Protein Levels Using ELISA in Both Chronic and Aggressive Periodontitis Patient. AB - BACKGROUND: Periodontitis can be defined as a local inflammatory process which mediates destruction of periodontal tissues & is triggered by bacterial insult. In periodontal infections, the levels of C reactive proteins are elevated as compared to the levels in a periodontally healthy individual. The study was done to determine the relative levels of serum CRP in aggressive, chronic and periodontally healthy subjects and to evaluate the effect of surgical periodontal therapy on serum C-reactive protein levels. MATERIALS AND METHODS: Serum samples were collected from 150 participants (50 healthy control patients (non periodontitis), 50 patients with chronic periodontitis and aggressive periodontitis. Serum C- reactive protein levels were assessed by means of immunoturbidimetric assay at baseline for subjects in all the 3 groups and 3 months after completion of surgical therapy. RESULTS: The mean baseline C reactive protein (CRP) concentrations in the Groups I, II and III were 1.65+/ 0.57 mg/L, 3.03+/-2.14 mg/L and 3.09+/-2.27 mg/L respectively. After treatment, the mean C-reactive protein (CRP) levels in Groups II and III reduced from 3.03+/ 1.67 mg/L to 1.46+/-1.67 mg/L and from 3.09+/-1.21 to 1.43+/-1.21 mg/L respectively. Similar results were found for probing depth and all indexes in Group II and III after treatment. Also, the mean attachment loss in Groups II and III reduced, so the results were highly significant. CONCLUSION: Successful periodontal treatment results in significant decrease in serum C-reactive protein (CRP) levels in otherwise healthy subjects. PMID- 26557606 TI - Influence of Media in the Choice of Oral Hygiene Products Used Among the Population of Maduravoyal, Chennai, India. AB - BACKGROUND AND AIMS: To assess the factors influencing the awareness and practice of oral hygiene among the local population Maduravoyal, Chennai, India. MATERIALS AND METHODS: A cross-sectional questionnaire based study was conducted to understand the factors influencing the choice and practice of oral hygiene products among the population of Maduravoyal, Chennai, India. Data was collected by means of a self administered structured questionnaire written in English and validated through a pilot survey. One thousand two hundred and nine subjects, with an age range of 15 to 70 years, who visited the Department of Periodontology, Meenakshi Ammal Dental College, Chennai were selected for investigation. The data obtained was analyzed using the SPSS version 13.0. The frequency of distribution and percentages were calculated. RESULTS: The results of the study showed that tooth brush (98.5%) and toothpaste (98%) were the main products used for the maintenance of oral hygiene and around 84.6% of the population brushed once daily. Information from the media (59.4%) and decay prevention (49.7%) were the major factors that influenced the choice of toothpaste among the study population. CONCLUSION: The major factor which influenced the choice of oral hygiene products was based on information obtained from advertisements and other sources. There is a need for the dental professionals to be aware of the ever-increasing development and marketing of oral hygiene products from various databases. Hence, the education of people regarding the importance of oral hygiene maintenance, proper selection of oral hygiene products is essential. PMID- 26557607 TI - Total and Free Fluoride Concentration in Various Brands of Toothpaste Marketed in India. AB - BACKGROUND: For fluoridated toothpaste to be effective in controlling dental caries, an adequate concentration of soluble fluoride must be available in the oral cavity. AIM: To determine the total and free fluoride concentration in various brands of toothpaste marketed in India. MATERIALS AND METHODS: Three samples of 12 different toothpastes were purchased from supermarkets in Mysore city, Karnataka, India. Toothpastes were analysed in duplicate using a fluoride ion-specific electrode. The concentration of total fluoride (TF) and total soluble fluoride (TSF) were determined. RESULTS: Measured TF was consistent with that declared by the manufacturer in five products. Four toothpastes showed lower TF and two higher TF than declared. Most toothpastes exhibited TSF concentrations similar to the TF content except four samples that displayed considerably lower TSF than TF. CONCLUSION: The measurement of total and free fluoride concentrations of toothpastes available in India showed inhomogenities. Therefore there is a need for stringent regulatory control measures for the determination of fluoride content in toothpastes in developing country like India. PMID- 26557608 TI - Efficacy of 0.25% Lemongrass Oil Mouthwash: A Three Arm Prospective Parallel Clinical Study. AB - BACKGROUND: Chlorhexidine mouthwash has earned eponym of gold standard to treat and/or prevent periodontal diseases. However, the present study was carried out to explore an alternative herbal mouthwash. AIM: To compare the anti-plaque and anti-gingivitis efficacy of a 0.25% lemongrass oil mouthwash to that of 0.2% chlorhexidine mouthwash. MATERIALS AND METHODS: A double-blinded parallel designed clinical trial with 60 subjects was taken for the study. Baseline plaque index (PI) & gingival index (GI) score was recorded. Oral prophylaxis was done and the plaque score was set at zero. Then, subjects were randomly allocated into 3 groups (N=20 in each): 0.25% lemongrass oil mouthwash, 0.2% chlorhexidine mouthwash and oral prophylaxis only. Subjects were asked to swish with respective mouthwash twice daily for 21 days. Subjects were again re-evaluated on 14(th) and 21(st) day for GI and PI. Comparison of the mean difference among the variables was performed by parametric tests. RESULTS: Lemongrass oil mouthwash group showed highest reduction in GI & PI at both 14(th) and 21(st) day, which was statistically significant (p<=0.05). CONCLUSION: Lemongrass oil mouthwash can also be used as a good herbal alternative to chlorhexidine mouthwash, so further studies are needed. PMID- 26557609 TI - Perception of Aesthetics by Different Professionals of Different Communities. AB - AIM: To evaluate the perception of aesthetics by different professionals of different communities in India by a photographic study. MATERIALS AND METHODS: This was a photographic study conducted among different professionals of different communities to establish an aesthetic norm for Indian population. The communities to which the professionals belonged were North Indian, South Indian, Maharashtrian, Gujarati and Parsi. The subjects photographed were aesthetic profiles with good occlusion. Five different facial photographic views each for male and female were obtained. These photographs were then subjected to changes in increments of 2 mm and 4 mm in retrusive and protrusive profile in Adobe Photoshop CS5 after which they were evaluated by different professionals of different communities according to their preference from most liked to least liked. RESULTS: The aesthetic preferences differed widely among different professionals of different community. CONCLUSION: The established aesthetic norms can be utilized by the dental fraternity in general and Orthodontist's in particular in diagnosis and treatment planning of Samples belonging to different communities to have the treatment outcome in unison with the established soft tissue norm for that particular community. PMID- 26557610 TI - Evaluation of Patients' Satisfaction after Class III Orthognathic Surgery. AB - BACKGROUND: Well-planned orthognathic surgery improves psychological health, aesthetics and function of patients. AIM: The present study aimed to investigate patients' satisfaction after orthognathic surgery by means of a satisfaction questionnaire before and after surgery. MATERIALS AND METHODS: A total of 29 patients was selected (17 women and 12 men), with a mean age of 28 years, randomly selected from a private clinic at Aracatuba - Sao Paulo by two investigators. Anamnesis and clinical examination were performed. Subjects with facial deformities submitted to orthodontic treatment before and after orthognathic surgery with a minimum post-surgery period of 6 months, answered a satisfaction questionnaire composed of 10 questions regarding dental and facial aesthetics. In this study, the maximum satisfaction score was 10. RESULTS: Regarding aesthetics, two satisfaction parameters were investigated: dental and facial. For all indices, the average satisfaction was up to score 7. CONCLUSION: According to the results, it can be concluded that orthognathic surgery has been an effective treatment for dentofacial deformities, aesthetics and functional problems, what was verified by pre and postoperative questionnaire application. PMID- 26557611 TI - Quantitative Analysis of Acute Phase Proteins in Post Chemo-Radiation Mucositis. AB - AIM: Oral mucositis induced by radiation is an inevitable but transient side effect of radiotherapy. Acute phase proteins are a class of proteins whose phase concentrations fluctuate in response to inflammation. The best known of the acute phase proteins is C-reactive protein, a protein that rises in the blood with inflammation. MATERIALS AND METHODS: 30 patients undergoing chemo - radiotherapy for head and neck cancer were clinically evaluated for mucositis on day 0, 7, 14, 28 and 42. Blood investigations like C-reactive protein, erythrocyte sedimentation rate and total leukocyte count were also conducted. RESULTS: There was a significant increase in the severity of mucositis during the course of treatment followed by a gradual decrease in severity towards the end of radiotherapy. Comparison of C-reactive protein levels from day 0 to day 42 in the study group showed a significant increase towards the end of radiotherapy. There was a significant increase in erythrocyte sedimentation rate levels till day 14 followed by a decrease towards the end of radiotherapy whereas total leukocyte count showed a significant decrease from day 0 to day 7 followed by an increase towards the end of radiotherapy. CONCLUSION: The oral mucosa bears only a small clinical spectrum of the side-effect conveyed by chemo-radiation. Both widespread and late effects do occur, and tissues may never return to normal completely. Inflammatory serum markers like C-reactive protein, erythrocyte sedimentation rate and total leukocyte count can thus be used as an objective measure to study the complexities of radiation mucositis which is documented as one of the worst side effects of head and neck cancer therapy. PMID- 26557612 TI - Fluoride Content of Bottled Drinking Water in Chennai, Tamilnadu. AB - CONTEXT: The optimum level of fluoride in drinking water is 0.7 to 1.2 ppm. Decreased fluoride concentration leads to increased risk of caries and increased concentration can lead to dental or skeletal fluorosis. One crore liters of water is supplied to Chennai and surrounding areas through pouches and bottles which carters about one third of city population. AIM: The aim of this study is to determine the fluoride concentration in top 10 bottled waters in Chennai and to check the accuracy of their labelling. MATERIALS AND METHODS: Top selling bottled waters, 6 multinational and 4 Non- multinational brands were selected for the study. Three different batches of each brand were purchased. The labels of the bottled were removed after collecting the details regarding fluoride content. All the bottles were numbered and sent for fluoride content analysis using SPADNS calorimetric method. RESULTS: All the brands and batches which were analysed for the study had less than optimal fluoride content and there is a significant variation in fluoride concentration of each brand and among different batches of same brand bottled waters. The range of fluoride level in tested samples was between 0.27 to 0.59. Only one brand's label had information regarding the fluoride content. CONCLUSION: Standardization of fluoride levels in bottled waters and labelling of fluoride content should become mandatory. PMID- 26557613 TI - Effects of Scaling and Root Planing on Gingival Status during Menstrual Cycle- A Cross-Sectional Analytical Study. AB - INTRODUCTION: Variations in sex steroid hormones, noticeable through the menstrual cycle of women, may impact periodontal health. A relationship between female sex hormone levels and periodontal changes during puberty, pregnancy, and menopause has been reported. Little research on gingival status at different periods of menstrual cycle, but very less work has been done to observe the effect of scaling on gingival status during different periods of menstrual cycle. MATERIALS AND METHODS: Thirty female subjects, aged 18-25 years were selected for a three month study. In Stage 1, clinical parameters {Plaque Index (PI), Gingival Index (GI), Modified Sulcular Bleeding Index (mSBI) and Probing depth (PD)} were recorded at three different time intervals {OV (Ovulation), PM (Premenstruation), M (Menstruation)} of their menstrual cycle, without scaling and polishing. In Stage 2, all clinical parameters were recorded at their subsequent menstrual cycle after scaling and polishing. RESULTS: In interstage analysis, OV 1 > OV 2, PM 1 > PM 2 and M 1> M 2. In intrastage analysis, for PI, mean difference between all values was not statistically significant. For mSBI, PM 1 > OV 1 > M 1, also PM 2 > OV 2 > M 2. For GI, PM 1 > OV 1 > M 1, also PM 2 > OV 2 > M 2. For PD, mean difference was not statistically significant. CONCLUSION: Ovarian hormones influence gingival status of females, with an increase observed primarily during PM and OV phases of menstrual cycle. Scaling leads to a subsequent decrease in gingival inflammation. PMID- 26557614 TI - Assessment of the Potential of CFC (Calcium hydroxide Flagyl Ciprofloxacin) for the Rapid Disinfection of Resilon and Gutta-Percha. AB - INTRODUCTION: Obturating materials exposed to the dental operating environment has been shown to be contaminated, making rapid chair side disinfection mandatory to ensure the sterility of the root canals. OBJECTIVE: The purpose of this study was to investigate the effectiveness of CFC (combination of Calcium hydroxide, Flagyl and Ciprofloxacin) for the rapid disinfection of Gutta-percha and Resilon cones. MATERIALS AND METHODS: Seventy new Gutta-percha and Resilon cones were randomly selected, contaminated with Enterococcus faecalis and divided into 4 group according to the irrigant used for disinfection {Group I: 5.25% Sodium Hypochlorite (NaOCl), Group II: MTAD, Group III: 2% Chlorhexidine (CHX), Group IV: CFC (a combination of Calcium hydroxide, Flagyl and Ciprofloxacin)}. All the samples were placed in a centrifuge tube with BHI broth after being washed with sterile water. The samples were then incubated for 7 days at 37(o)C. Samples were randomly plated on Mac Conkey agar plate and the colony count was recorded and the observations were drawn. RESULTS: A 5.25% NaOCl required 1 minute exposure for effective disinfection of all the samples. MTAD could eliminate E.faecalis from gutta-percha samples in 30 seconds whereas it required 1 minute of exposure for Resilon cones. Both 2% CHX and CFC could not disinfect the samples with 1 minute exposure and a minimum of 5 minute exposure was required. CONCLUSION: A 5.25% NaOCl and Biopure MTAD required less chair side time to disinfect all the samples effectively when compared with 2% CHX and CFC. PMID- 26557615 TI - The Mystery of Handprints: Assesment and Correlation of Dermatoglyphics with Early Childhood Caries A Case-Control Study. AB - BACKGROUND: It has been acknowledged that genetics play a significant role in determination of dermatoglyphic patterns. Since caries is a multifactorial disease with the influence of genetic pattern, this study was undertaken to assess dermatoglyphic patterns and correlate them with early childhood caries. AIM: The aim of the study was to determine the association and correlation of dermatoglyphic patterns with early childhood caries. MATERIALS AND METHODS: The study sample consisted of 100 children aged between 3 and 6 years, divided into two groups of 50 children each. The deft score was evaluated to select the experimental group and control group. Finger and palm prints were recorded using the ink method described by Cummins and Midlo. The handprints obtained were checked for their clarity with a magnifying glass (*2) and coded. The presence of core and the triradii of the dermatoglyphic pattern were checked thoroughly to include the handprint in the study. A total of 1000 digital prints and 200 palmar prints were obtained. RESULTS: The presence of whorls in the index finger of the right hand predicts significantly lower risk of caries in children (male and female; combined). Presence of whorls in the ring finger of the right hand predicts significantly lower risk of caries in female children. Statistically no correlation between atd angle and early childhood caries was obtained from the present data. CONCLUSION: The results obtained from the present study creates a notion on the validity of the results of the previous studies and point them to be chance findings. Due to increasing acceptability of dermatoglyphics as a diagnostic tool for congenital diseases, further large scale extensive research should be undertaken to evaluate the role of the same in children with Early Childhood Caries (ECC). PMID- 26557616 TI - Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis. AB - BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. AIM: The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. MATERIALS AND METHODS: The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. RESULTS: Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. CONCLUSION: The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients. PMID- 26557617 TI - Invitro Study of the Effect of Different Samples of Water Used for Washing the Etchant on Bracket Bond Strength. AB - BACKGROUND: Bonding is a very important step in the orthodontic treatment planning. Effective bonding enhances the treatment by reducing the bond failure and thereby reducing the treatment duration and also increases efficiency in orthodontic mechanics. The success of the bonded brackets is negatively affected by contamination with oral fluids such as blood and saliva. AIM: The aim of the present study was to evaluate the effect of hardness of water used in removing the etchant on the bracket bond strength. MATERIALS AND METHODS: Seventy five extracted premolars were divided in three groups of 25 each. The teeth in all the three groups were etched with 35% phosphoric acid. The etchant in each of the group I, II and III was removed using distilled water (soft), corporation water (moderately hard) and hard water respectively. Stainless steel brackets were attached using light cure bonding agent (transbond XT, 3M UNITEK) and cured for 10sec with a light cure unit. The shear bond strength was evaluated by mechanical testing machine. Statistically significant differences were defined for p < 0.05. RESULT: The results showed significant increase in bond strength in samples where in soft water was used for cleaning the etchant on the bonding surface. CONCLUSION: Hardness of water used for washing the etchant affects the bracket bond strength. Shear bond strength of soft water is significantly increased compared to moderately hard and very hard water. PMID- 26557618 TI - The Comparative Evaluation of Patient's Satisfaction and Comfort Level by Diode Laser and Scalpel in the Management of Mucogingival Anomalies. AB - BACKGROUND: Surgical correction of mucogingival anomalies is required to enhance patient's compatibility to maintain oral hygiene or to improve facial aesthetics or both. Laser has become a desirable and dependable alternative for traditional surgical techniques because it is simple and painless with more predictable outcomes. AIM: The aim of this study was to compare the effects of the conventional scalpel technique and the laser technique on the degree of discomfort, satisfaction, healing and postoperative pain experienced by patients after correction of mucogingival anomalies. MATERIALS AND METHODS: In the present study 70 patients were enrolled and randomly distributed in two groups i.e. surgical correction of mucogingival anomalies by scalpel and by laser. Patient's comfort level, pain and satisfaction level was assessed by using Visual analogue scale (VAS) and healing was evaluated by healing index. RESULTS: The results indicated patients treated with the diode laser had less postoperative pain and discomfort with remarkable satisfactory results and healing compared to patients treated with the conventional technique. CONCLUSION: Laser is a desirable therapeutic alternative to correct soft tissue anomalies. It allows good control of haemorrhage with comfortable healing phase and appreciable satisfactory outcomes. PMID- 26557619 TI - Arthrocentesis A Minimally Invasive Method for TMJ Disc Disorders - A Prospective Study. AB - BACKGROUND: Temporomandibular joint (TMJ) disc disorders are one of the major concerns to the mankind and doctors in day to day life due to its complex nature and failure to treat these kinds of conditions successfully. OBJECTIVES: The aim of the present study was to evaluate the efficacy of arthrocentesis in patients suffering from TMJ disc disorders. MATERIALS AND METHODS: A total of 50 subjects suffering from TMJ disc disorders were selected and treated by arthrocentesis. The subjects were followed up for a period of one year. RESULTS: The mean maximal mouth opening prior to arthro-centesis was 32.13mm and after the procedure the mean maximal mouth opening was 46.6mm. The mean right and left lateral movements before arthrocentesis were 7.15mm and 7.59mm respectively, and the mean right and left lateral movements of 9.49 and 9.31 respectively were present after the procedure. The mean degree of pain before arthrocentesis was 8.7, and after the procedure the mean degree of pain was 1.13 as per the visual analogue scale. CONCLUSION: The findings of this study suggested potential utility of arthrocentesis in the management of TMJ disc disorders. PMID- 26557620 TI - Assessment of Fluoride Concentration of Soil and Vegetables in Vicinity of Zinc Smelter, Debari, Udaipur, Rajasthan. AB - BACKGROUND: As of late, natural contamination has stimulated as a reaction of mechanical and other human exercises. In India, with the expanding industrialization, numerous unsafe substances are utilized or are discharged amid generation as cleans, exhaust, vapours and gasses. These substances at last are blended in the earth and causes health hazards. OBJECTIVE: To determine concentration of fluoride in soils and vegetables grown in the vicinity of Zinc Smelter, Debari, Udaipur, Rajasthan. MATERIALS AND METHODS: Samples of vegetables and soil were collected from areas situated at 0, 1, 2, 5, and 10 km distance from the zinc smelter, Debari. Three samples of vegetables (i.e. Cabbage, Onion and Tomato) and 3 samples of soil {one sample from the upper layer of soil (i.e. 0 to 20 cm) and one from the deep layer (i.e. 20 - 40 cm)} at each distance were collected. The soil and vegetable samples were sealed in clean polythene bags and transported to the laboratory for analysis. One sample each of water and fertilizer from each distance were also collected. RESULTS: The mean fluoride concentration in the vegetables grown varied between 0.36 +/- 0.69 to 0.71 +/- 0.90 ppm. The fluoride concentration in fertilizer and water sample from various distances was found to be in the range of 1.4 - 1.5 ppm and 1.8 - 1.9 ppm respectively. CONCLUSION: The fluoride content of soil and vegetables was found to be higher in places near to the zinc smelter. PMID- 26557621 TI - Impact of Dental Neglect Scale on Oral Health Status Among Different Professionals in Indore City-A Cross- Sectional Study. AB - BACKGROUND: Young educated Indian generation are very much health conscious. They take adequate nutritious balanced diet and practice physical exercise regularly to keep themselves active and healthy. Oral health is a part of general health care system. If oral health is neglected it may affect our general health and as a result it affects our quality of life too. AIM: To assess dental negligence and oral health status by using Dental Neglect scale questionnaire among different professionals of Indore city. MATERIALS AND METHODS: The study consisted of a convenient sample of 400 students of aged 18-25 years from 4 different professional colleges of Sri Aurobindo Group of Institutes of the same campus. A pretested validated questionnaire was used for assessing dental neglect and home dental care practices. Oral health examination was conducted to assess dental caries and oral hygiene status by using DMFT and OHIS respectively. Data was analysed using SPSS Software (version 20). RESULTS: For OHI(S), majority of the respondents (57.7%) showed fair oral hygiene for DNS score <15, whereas majority of the professionals (63.7%), showed poor oral hygiene for DNS score >15. The Dental Neglect Scale (DNS) score was found statistically significant with OHIS and caries experience at 95% Confidence Interval. There was no statistically significant difference between DNS score and frequency of Decayed, Missing and Filled teeth DMFT. CONCLUSION: The Dental Neglect Scale appears to be a sound method for objectifying dental neglect. It has many of the features of a satisfying health index. However, further validation with other age groups, cultures, place and a larger population is required in order to justify the utility of Dental Neglect Scale in different situations. PMID- 26557622 TI - Prevalence and Association of Developmental Defects of Enamel with, Dental- Caries and Nutritional Status in Pre-School Children, Lucknow. AB - BACKGROUND: Developmental Defects of Enamel in the primary dentition may be associated and predictors of dental caries and nutritional status. The aim of the present study was to assess the Prevalence of Developmental Defects of Enamel and its Association with, Dental-Caries and Nutritional Status in Pre-School Children of Lucknow, India. MATERIALS AND METHODS: Multistage Sampling was done. A total of 302 pre-school (Rural and Urban) children were examined. Type III examination was conducted with WHO Probe. Developmental Enamel Defects (DED) and Dental Caries were assessed using WHO (1997) Proforma. RESULTS: The prevalence of DED of any type was 39.9% with that of demarcated opacities being the highest, followed by hypoplasia. The most frequently affected teeth were maxillary anterior teeth, while the least affected teeth were mandibular incisors. The mean dmft was 3.5. A positive association between DED and caries was observed. Association between Dental Caries & BMI was non-significant whereas Pearson correlation showed a negative correlation between the two. CONCLUSION: The prevalence of enamel defects and caries was high, as the enamel defects were strongly associated with caries. PMID- 26557623 TI - Effectiveness of Various Sensory Input Methods in Dental Health Education Among Blind Children- A Comparative Study. AB - AIM: The aim of the study is to evaluate effectiveness of various sensory input methods in dental health education among blind children. Oral hygiene status was assessed through visible plaque index and oral hygiene knowledge was assessed through questionnaire before and after oral health education. MATERIALS AND METHODS: The study involved of 200 blind children with the age range of 8 to 14 years of both genders from two blind schools similar in standard of teaching. The total study population (n=200) was randomized and divided into five Groups, comprising of 40 children in each Group. The first four were the experimental Groups who received dental health education through different modes, while the fifth Group served as control. Oral health related knowledge and plaque scores were assessed in all the study Groups before and after dental health education. RESULTS: After intervention, the mean knowledge scores and plaque scores were statistically significant in all the study Groups when compared to the baseline scores. CONCLUSION: The present study proved that blind children can maintain an acceptable level of oral hygiene when taught with special customized methods like multisensory approach with creative use of other senses which was found to be effective than unisensory method. PMID- 26557624 TI - Improving Gingival Aesthetics Using Platelet Rich Fibrin and Synthetic Collagen Membrane: A Report of Two Cases. AB - Covering the clinically exposed root surface of a tooth has now become a routine demand of patients to improve aesthetics and also to reduce the instances of hypersensitivity. The idea behind the treatment of gingival recession is to place the gingiva as close as possible to the cement-enamel junction so that the exposed root area is covered and a normal sulcus is created. Here we present a series of two cases of gingival recession treatment in young patients affecting the maxillary anterior region. The affected sites were treated by a periodontal flap with synthetic collagen membrane and patient derived platelet rich fibrin. It may be emphasized that platelet-rich fibrin can be used as a membrane for periodontal tissue regeneration and it has the ability to promote platelet aggregation, be chemotactic for fibroblast and enhance wound stability and proper healing. Hence, both the methods can be successfully used in place of a connective tissue graft for treating gingival recession. PMID- 26557625 TI - A Rare Entity of Giant Epidermal Exophytic Naevus of Hemifacial Region. AB - The term nevi constitute a hamartomatous growth of either skin or mucosa that is generally found at birth or shortly after birth. An epidermal nevus consisting chiefly of sebaceous glands is called as nevus sebaceous. Typically this entity is seen as a solitary bald patch over the scalp at birth. We report a case of exophytic lesion following blaschko's lines at birth. We find this case as peculiar because of the multiplicity of lesions, their pattern of distribution, as well as their atypical morphology. PMID- 26557626 TI - Keratoacanthoma of Upper Lip: Review and Report of Case Managed Surgically. AB - Keratoacanthoma is a benign lesion usually presenting as a solitary, dome shaped nodule with a central crater filled with keratin. It frequently occurs on the sun exposed areas of the skin. Keratoacanthoma can be difficult to differentiate from oral squamous cell carcinoma both clinically and microscopically. A case of keratoacanthoma involving the upper lip in a 51-year-old male is reported presenting as an exophytic growth that resolved after excisional biopsy. PMID- 26557627 TI - A Case of Intraoral Lymphangioma Circumscripta - A Diagnostic Dilemma. AB - Lymphangiomas are developmental malformations which present as benign hamartomas of lymphatic channels. They are commonly located in the head and neck region and are less frequently reported in the oral cavity. However affected sites in the oral cavity include the tongue, palate, gingiva, buccal mucosa, lips and alveolar ridge of the mandible. The most common site in the oral cavity is tongue. Lymphangioma of the buccal mucosa is rare as per the available literature and they usually occur as lobular masses or cystic lesions. Histopathologically, lymphangioma appear as proliferated lymphatic vessels lined by plump endothelial cells. Surgical excision, laser therapy and sclerotherapy are the eventual modes of treatment. This paper reports a rare case of lymphangioma of the buccal mucosa in a 60-year old male patient managed by surgical excision. PMID- 26557628 TI - Facilitated Eruption of an Impacted Premolar 8 Years Post-eruption Timing- Think before You Treat!!! AB - The treatment planning of impacted teeth usually involves surgical intervention for bringing about its eruption with traction. But a thoughtful analysis in such cases looking at the possible aetiology may save the complexity of therapy. The present case demonstrates the importance of correct diagnosis in resolving impaction wherein an impacted mandibular second premolar was made to erupt using a simple removable appliance 8 years after its normal range of eruption timing. PMID- 26557629 TI - Severely Resorbed Edentulous Ridges: A Preventive Prosthodontic Approach - A Case Report. AB - As a dentist our main aim should be prevention which not only includes prevention of caries and or periodontal disease but also prevention of residual alveolar bone loss after teeth are extracted. Today with greater stress on preventive measures, the dental profession has expanded this preventive concept into Prosthodontics. Preventive Prosthodontics emphasizes the importance of any procedure that can delay or eliminate the future Prosthodontic problem and stop further progression of oral disease and prevent the loss of remaining tissues. The Residual Ridge Resorption (RRR) is an inevitable consequence of tooth loss and denture wearing. Severe RRR gradually results in increased interarch distance, significant horizontal discrepancy between edentulous ridges, occurrence of flabby displaceable tissues in the denture bearing area and other sequelae. Prosthetic rehabilitation in these patients can be challenging. The conventional complete denture fabrication in such cases may further compound the poor denture bearing ability of the tissues and lead to decreased retention, stability and support which may result in psychological problems and social isolation. This case report emphasizes the importance of preventive concepts in every step of complete denture fabrication to offer a long serviceable prosthesis without any significant complications and compromise. PMID- 26557630 TI - Modified SARME (Surgically Assisted Rapid Maxillary Expansion) in Conjunction with Orthodontic Treatment-A Case Report. AB - Transverse maxillary hypoplasia or maxillary constriction in conjunction with unilateral or bilateral posterior cross bites is a common finding in cleft palate patients. These situations are also commonly encountered in adults who have not had recourse to orthodontic treatment in childhood. In adults, after ossification of the mid palatal suture is complete, the accepted means of correcting transverse skeletal discrepancies is by Surgically Assisted Rapid Maxillary Expansion (SARME). The disadvantage of this technique in the Indian scenario is reduced patient acceptance and increased treatment costs. Le Fort-I down fracture and mid palatal suture sectioning requires hospitalization and increases morbidity. A case of a 21-year-old non-cleft male who presented with Class I malocclusion with transverse skeletal discrepancy and bilateral posterior cross bites is presented. A modified SAARME technique was performed without pterygomaxillary disjunction, as an outpatient procedure. The results obtained were satisfactory and the desired amount of transverse skeletal correction was achieved. The patient was discharged the same day. The technique can be used to successfully treat a large number of patients in India with maxillary skeletal transverse problems with increased predictability, reduced costs and morbidity and higher rates of acceptance. PMID- 26557631 TI - A Novel Approach to Regain Anterior Space Using Modified 2 by 3 Fixed Appliance: A Report of Two Cases. AB - Early loss of permanent anterior teeth in growing children has a psychological impact on the child. Anterior teeth are important both aesthetically and functionally. When a permanent tooth is lost, the teeth adjacent to the created space tend to migrate into the space resulting in the space loss. Management of regaining space with the removable appliance always depends on child cooperation for using the appliance as well as for the recall visits. The advantages of fixed appliances over the removable appliances are minimal discomfort, reduced need for patient cooperation and increased control of tooth movements in all three directions of space. Thus, a short course of fixed appliance like the modified 2 by 3 fixed appliance followed by fixed functional space maintainer could be an ideal treatment option for such cases. PMID- 26557632 TI - Atypical Presentation of Capillary Hemangioma in Oral Cavity- A Case Report. AB - Capillary Haemangioma is a benign vascular tumour characterized by proliferation of blood vessels that are primarily reported to be a developmental hamartomatous lesion of infancy and childhood. Pyogenic granuloma is a non-neoplastic benign lesion found in the oral cavity having a striking predilection for occurrence in the gingiva. The present case report is an atypical presentation of capillary haemangioma on gingiva which is considered to be extremely rare. The lesion in this case was clinically diagnosed as pyogenic granuloma but histopathologically as capillary haemangioma. These lesions present as a diagnostic dilemma to the clinician and can lead to serious complications if not carefully managed. PMID- 26557633 TI - Curcumin - Pharmacological Actions And its Role in Oral Submucous Fibrosis: A Review. AB - Turmeric has been in use for thousands of years as a dye, flavouring and a medicinal herb. Ancient Indian medicine has touted turmeric as an herb with the ability to provide glow and lustre to the skin as well as vigour and vitality to the entire body. Since curcumin has antimicrobial, antioxidant, astringents and other useful properties, it is quite useful in dentistry also. Curcumin, the most active polyphenolic constituent, is the active ingredient in the traditional herbal remedy and dietary spice turmeric. In gel form it is a component in local drugs delivery system. The objective of this article is to review the pharmacological action of turmeric and its use in treating oral submucous fibrosis. PMID- 26557635 TI - Oral Squamous Cell Carcinoma: Picro Sirius Red Stain. PMID- 26557634 TI - Allergic Reactions to Dental Materials-A Systematic Review. AB - INTRODUCTION: Utility of various dental materials ranging from diagnosis to rehabilitation for the management of oral diseases are not devoid of posing a potential risk of inducing allergic reactions to the patient, technician and dentist. This review aims to develop a systematic approach for the selection and monitoring of dental materials available in the market thereby giving an insight to predict their risk of inducing allergic reactions. MATERIALS AND METHODS: Our data included 71 relevant articles which included 60 case reports, 8 prospective studies and 3 retrospective studies. The source of these articles was Pub Med search done with the following terms: allergies to impression materials, sodium hypochlorite, Ledermix paste, zinc oxide eugenol, formaldehyde, Latex gloves, Methyl methacrylate, fissure sealant, composites, mercury, Nickel-chromium, Titanium, polishing paste and local anaesthesia. All the relevant articles and their references were analysed. The clinical manifestations of allergy to different dental materials based on different case reports were reviewed. RESULTS: After reviewing the literature, we found that the dental material reported to cause most adverse reactions in patients is amalgam and the incidence of oral lichenoid reactions adjacent to amalgam restorations occur more often than other dental materials. CONCLUSION: The most common allergic reactions in dental staff are allergies to latex, acrylates and formaldehyde. While polymethylmethacrylates and latex trigger delayed hypersensitivity reactions, sodium metabisulphite and nickel cause immediate reactions. Over the last few years, due to the rise in number of patients with allergies from different materials, the practicing dentists should have knowledge about documented allergies to known materials and thus avoid such allergic manifestations in the dental clinic. PMID- 26557636 TI - Miles to Discover in Histological Grading of Odontogenic Tumours. PMID- 26557637 TI - Desmoplastic Ameloblastoma - An Unusual Presentation. AB - Ameloblastomas are the most common and represents a family of diseases with diverse biological behaviour and contribute to 11-18% of odontogenic epithelial neoplasms. Downstream it has been regarded as benign neoplasm with local aggressiveness. Desmoplastic ameloblastoma is the least frequent of all the variants of ameloblastoma and contribute to 4-5%. The uniqueness of this lesion can be further enhanced with respect to its site of occurrence and the radiographic features in contrast to the classical type of ameloblastoma. Here in, we report a case of Desmoplastic Ameloblastoma in anterior mandible in a 65 year-old male crossing the midline, which deserves preponderency because of its distinct site, radiological features, local aggressiveness and high chances of false clinical impression. This case report is an effort to develop a high index of suspicion in diagnosing such rare cases. PMID- 26557638 TI - Heterotopic Tooth: An Exceptional Entity. PMID- 26557639 TI - Quality of Life and Related Factors Among People With Spinal Cord Injuries in Tehran, Iran. AB - BACKGROUND: Spinal Cord Injury (SCI) is one of the biggest health problems. Disabilities resulting from injuries such as spinal disability requires special attention because of their potential reduced to cause adverse effects in different systems of the body. Today, improving the Quality of Life (QOL) in patients with SCIs is an important goal of treatment. OBJECTIVES: The purpose of this study was to determine the QOL and related factors among people with SCIs. PATIENTS AND METHODS: In this cross-sectional descriptive study, 106 patients with SCI were selected through sampling based on census. Data were collected using a demographic questionnaire and a Short-Form 36 (SF-36) health survey questionnaire for measuring the QOL among patients. Data were analyzed using SPSS 14 software and descriptive and inferential statistics. P < 0.05 was considered statistically significant. RESULTS: The mean QOL in these patients was 37.1 +/- 1.7 years (21 - 65 years) and mean disease duration was 7.3+/-6 years. The most common injury was paraplegia. Most of the patients have moderate QOL (54.7 %). The results showed a significant relationship between QOL and marital status and employment status (P < 0.05). Also, results showed a significant relationship between QOL and education levels (P = 0.002), age (P = 0.001), and duration of illness (P = 0.001).The highest and lowest scores were 64 +/- 7.1 and 36 +/- 5.3 for understanding General Health (GH) and role physical, respectively. CONCLUSIONS: The results show that patients with SCI have a moderate health related QOL Determining the QOL is needed to focus on the strengths and weaknesses of patients with spinal cord injuries. Planning principles is recommended in order to reform the disability. PMID- 26557640 TI - Synthetic self-adjuvanting glycopeptide cancer vaccines. AB - Due to changes in glycosyltransferase expression during oncogenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens (TACAs), and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system toward tumor-associated glycopeptide antigens via synthetic self-adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Many of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo. PMID- 26557641 TI - Lifetime Distributions from Tracking Individual BC3H1 Cells Subjected to Yessotoxin. AB - This work shows examples of lifetime distributions for individual BC3H1 cells after start of exposure to the marine toxin yessotoxin (YTX) in an experimental dish. The present tracking of many single cells from time-lapse microscopy data demonstrates the complexity in individual cell fate and which can be masked in aggregate properties. This contribution also demonstrates the general practicality of cell tracking. It can serve as a conceptually simple and non intrusive method for high throughput early analysis of cytotoxic effects to assess early and late time points relevant for further analyzes or to assess for variability and sub-populations of interest. The present examples of lifetime distributions seem partly to reflect different cell death modalities. Differences between cell lifetime distributions derived from populations in different experimental dishes can potentially provide measures of inter-cellular influence. Such outcomes may help to understand tumor-cell resistance to drug therapy and to predict the probability of metastasis. PMID- 26557642 TI - Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants. AB - Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions. PMID- 26557644 TI - Distribution and Viability of Fetal and Adult Human Bone Marrow Stromal Cells in a Biaxial Rotating Vessel Bioreactor after Seeding on Polymeric 3D Additive Manufactured Scaffolds. AB - One of the conventional approaches in tissue engineering is the use of scaffolds in combination with cells to obtain mechanically stable tissue constructs in vitro prior to implantation. Additive manufacturing by fused deposition modeling is a widely used technique to produce porous scaffolds with defined pore network, geometry, and therewith defined mechanical properties. Bone marrow-derived mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering based cell therapies due to their multipotent character. One of the hurdles to overcome when combining additive manufactured scaffolds with MSCs is the resulting heterogeneous cell distribution and limited cell proliferation capacity. In this study, we show that the use of a biaxial rotating bioreactor, after static culture of human fetal MSCs (hfMSCs) seeded on synthetic polymeric scaffolds, improved the homogeneity of cell and extracellular matrix distribution and increased the total cell number. Furthermore, we show that the relative mRNA expression levels of indicators for stemness and differentiation are not significantly changed upon this bioreactor culture, whereas static culture shows variations of several indicators for stemness and differentiation. The biaxial rotating bioreactor presented here offers a homogeneous distribution of hfMSCs, enabling studies on MSCs fate in additive manufactured scaffolds without inducing undesired differentiation. PMID- 26557645 TI - Food Science without Borders. PMID- 26557643 TI - Engineering of Metabolic Pathways by Artificial Enzyme Channels. AB - Application of industrial enzymes for production of valuable chemical compounds has greatly benefited from recent developments in Systems and Synthetic Biology. Both, in vivo and in vitro systems have been established, allowing conversion of simple into complex compounds. Metabolic engineering in living cells needs to be balanced which is achieved by controlling gene expression levels, translation, scaffolding, compartmentation, and flux control. In vitro applications are often hampered by limited protein stability/half-life and insufficient rates of substrate conversion. To improve stability and catalytic activity, proteins are post-translationally modified and arranged in artificial metabolic channels. Within the review article, we will first discuss the supramolecular organization of enzymes in living systems and second summarize current and future approaches to design artificial metabolic channels by additive manufacturing for the efficient production of desired products. PMID- 26557646 TI - Prevention of a Parastomal Hernia by Biological Mesh Reinforcement. AB - INTRODUCTION: In the field of hernia prevention, the prophylactic mesh reinforcement of stoma-sites is one of the most controversially discussed issues. The incidence of parastomal hernias in the literature reported to be up to 48.1% after end colostomy and up to 30.8% after loop of colostomy, but still remains uncertain due to diagnostic variety of clinical or radiological methods, heterogeneous patient groups and variable follow-up intervals. Anyway, the published data regarding the use of synthetic or bio-prostethic meshes in the prevention of parastomal hernia at the primary operation are very scarce. METHODS: A literature search of the Medline database in terms of biological prophylactic mesh implantation in stoma creation identified six systematic reviews, two randomized controlled trials (RCT), two case-controlled studies, and one technical report. RESULTS: In a systematic review focusing on the prevention of parastomal hernia including only RCTs encompassing one RCT using bio prosthetic mesh the incidence of herniation was 12.5% compared to 53% in the control group (p < 0.0001). In one RCT and two case-control studies, respectively, there was a significant smaller incidence of parastomal herniation as well as a similar complication rate compared to the control group. Only in one RCT, no significant difference regarding the incidence of parastomal hernia was reported with comparable complication rates. CONCLUSION: Thus, so far two RCT and two case-control studies are published with prophylactic bio-prosthetic reinforcement in stoma sites. The majority revealed significant better results in terms of parastomal herniation and without any mesh-related complications in comparison to the non mesh group. Further, multicenter RCT are required to achieve a sufficient level of recommendation. PMID- 26557647 TI - Assessment of Gate Width Size on Lifetime-Based Forster Resonance Energy Transfer Parameter Estimation. AB - Forster Resonance Energy Transfer (FRET) enables the observation of interactions at the nanoscale level through the use of fluorescence optical imaging techniques. In FRET, fluorescence lifetime imaging can be used to quantify the fluorescence lifetime changes of the donor molecule, which are associated with proximity between acceptor and donor molecules. Among the FRET parameters derived from fluorescence lifetime imaging, the percentage of donor that interacts with the acceptor (in proximity) can be estimated via model-based fitting. However, estimation of the lifetime parameters can be affected by the acquisition parameters such as the temporal characteristics of the imaging system. Herein, we investigate the effect of various gate widths on the accuracy of estimation of FRET parameters with focus on the near-infrared spectral window. Experiments were performed in silico, in vitro, and in vivo with gate width sizes ranging from 300 ps to 1000 ps in intervals of 100 ps. For all cases, the FRET parameters were retrieved accurately and the imaging acquisition time was decreased three-fold. These results indicate that increasing the gate width up to 1000 ps still allows for accurate quantification of FRET interactions even in the case of short lifetimes such as those encountered with near-infrared FRET pairs. PMID- 26557648 TI - A New Binning Method for Metagenomics by One-Dimensional Cellular Automata. AB - More and more developed and inexpensive next-generation sequencing (NGS) technologies allow us to extract vast sequence data from a sample containing multiple species. Characterizing the taxonomic diversity for the planet-size data plays an important role in the metagenomic studies, while a crucial step for doing the study is the binning process to group sequence reads from similar species or taxonomic classes. The metagenomic binning remains a challenge work because of not only the various read noises but also the tremendous data volume. In this work, we propose an unsupervised binning method for NGS reads based on the one-dimensional cellular automaton (1D-CA). Our binning method facilities to reduce the memory usage because 1D-CA costs only linear space. Experiments on synthetic dataset exhibit that our method is helpful to identify species of lower abundance compared to the proposed tool. PMID- 26557649 TI - SimpLiFiCPM: A Simple and Lightweight Filter-Based Algorithm for Circular Pattern Matching. AB - This paper deals with the circular pattern matching (CPM) problem, which appears as an interesting problem in many biological contexts. CPM consists in finding all occurrences of the rotations of a pattern ?? of length m in a text ?? of length n. In this paper, we present SimpLiFiCPM (pronounced "Simplify CPM"), a simple and lightweight filter-based algorithm to solve the problem. We compare our algorithm with the state-of-the-art algorithms and the results are found to be excellent. Much of the speed of our algorithm comes from the fact that our filters are effective but extremely simple and lightweight. PMID- 26557650 TI - Systemic and Ocular Hemodynamic Risk Factors in Glaucoma. AB - Primary open angle glaucoma (POAG) is a multifactorial disease characterized by progressive retinal ganglion cell death and visual field loss. It is known that alterations in intraocular pressure (IOP), blood pressure (BP), and ocular perfusion pressure (OPP) can play a significant role in the pathogenesis of the disease. Impaired autoregulatory capacity of ocular blood vessels may render tissues vulnerable to OPP changes and potentially harmful tissue ischemia reperfusion damage. Vascular risk factors should be considered more important in a subgroup of patients with POAG, and especially in patients with normal tension glaucoma (NTG) with evidence of unphysiological BP response. For example, reduction of BP during the nighttime has an influence on OPP, and increased circadian OPP fluctuation, which might stand for unstable ocular blood flow, has been found to be the consistent risk factor for NTG development and progression. Central visual field may be affected more severely than peripheral visual field in NTG patients with higher 24-hour fluctuation of OPP. This review will discuss the current understanding of allegedly major systemic and ocular hemodynamic risk factors for glaucoma including systemic hypertension, arterial stiffness, antihypertensive medication, exaggerated nocturnal hypotension, OPP, and autonomic dysregulation. PMID- 26557651 TI - Cementation of Glass-Ceramic Posterior Restorations: A Systematic Review. AB - AIM: The aim of this comprehensive review is to systematically organize the current knowledge regarding the cementation of glass-ceramic materials and restorations, with an additional focus on the benefits of Immediate Dentin Sealing (IDS). MATERIALS AND METHODS: An extensive literature search concerning the cementation of single-unit glass-ceramic posterior restorations was conducted in the databases of MEDLINE (Pubmed), CENTRAL (Cochrane Central Register of Controlled Trials), and EMBASE. To be considered for inclusion, in vitro and in vivo studies should compare different cementation regimes involving a "glass ceramic/cement/human tooth" complex. RESULTS AND CONCLUSIONS: 88 studies were included in total. The in vitro data were organized according to the following topics: (micro)shear and (micro)tensile bond strength, fracture strength, and marginal gap and integrity. For in vivo studies survival and quality of survival were considered. In vitro studies showed that adhesive systems (3-step, etch-and rinse) result in the best (micro)shear bond strength values compared to self adhesive and self-etch systems when luting glass-ceramic substrates to human dentin. The highest fracture strength is obtained with adhesive cements in particular. No marked clinical preference for one specific procedure could be demonstrated on the basis of the reviewed literature. The possible merits of IDS are most convincingly illustrated by the favorable microtensile bond strengths. No clinical studies regarding IDS were found. PMID- 26557652 TI - Retrobulbar Hemodynamics and Visual Field Progression in Normal Tension Glaucoma: A Long-Term Follow-Up Study. AB - PURPOSE: Vascular risk factors are important factors in the pathogenesis of glaucoma. The purpose of this research was to investigate retrobulbar hemodynamics and visual field progression in patients with normal tension glaucoma (NTG). PATIENTS AND METHODS: 31 eyes of 16 patients with NTG were included in a retrospective long-term follow-up study. Colour Doppler imaging was performed at baseline to determine various CDI parameters in the different retrobulbar vessels. The rate of visual field progression was determined using the Visual Field Index (VFI) progression rate per year (in %). To be included in the analysis, patients had at least 4 visual field examinations with a follow-up of at least 2 years. RESULTS: Mean follow-up was 7.6 +/- 4.1 years with an average of 10 +/- 5 visual field tests. The mean MD (mean defect) at baseline was -7.61 +/- 7.49 dB. The overall VFI progression was -1.14 +/- 1.40% per year. A statistical significant correlation between VFI progression and the RI of the NPCA and PSV of the CRA was found. CONCLUSION: Long-term visual field progression may be linked to impaired retrobulbar hemodynamics in patients with NTG only to a limited degree. Interpretation of the data for an individual patient seems to be limited due to the variability of parameters. PMID- 26557654 TI - Validation of Screening Questions for Hyperacusis in Chronic Tinnitus. AB - BACKGROUND: We investigated the validity of the two hyperacusis items of the TSCHQ (Tinnitus Sample Case History Questionnaire) from the TRI (Tinnitus Research Initiative) database by comparing them with the German hyperacusis questionnaire GUF. METHODS: We investigated the association of the GUF with the TSCHQ screening questions for both the sum score and the single items with correlation, contrast, principal component, and discriminant analysis in a sample of 161 patients with chronic tinnitus. RESULTS: TSCHQ items and the GUF total score were significantly associated with a special focus on fear and pain related hyperacusis. Factor analysis of the GUF revealed the three factors "fear and pain related hyperacusis," "hearing related problems," and "problems in quality of life." A discriminant analysis showed a sensitivity of 64% and a specificity of 71% of the TSCHQ items for the establishment of tinnitus patient subgroups with and without hyperacusis. DISCUSSION: Both hyperacusis TSCHQ items can serve as screening questions with respect to self-reported hyperacusis in chronic tinnitus with a specific focus on fear and pain related hyperacusis. However, the multiple dimensions of hyperacusis should be considered for diagnosis and treatment in both scientific and clinical contexts. PMID- 26557655 TI - An Evaluation of the Policy Context on Psychosocial Risks and Mental Health in the Workplace in the European Union: Achievements, Challenges, and the Future. AB - Despite the developments both in hard and soft law policies in the European Union in relation to mental health and psychosocial risks in the workplace, a review of these policies at EU level has not been conducted to identify strengths, weaknesses, and gaps to be addressed in the future. Keeping in mind that the aim should be to engage employers in good practice, ideally such policies should include key definitions and elements of the psychosocial risk management process, covering risk factors, mental health outcomes, risk assessment and preventive actions, or interventions. The current paper aims to fill this gap by reviewing hard and soft law policies on mental health in the workplace and psychosocial risks applicable at EU level and conducting a gap analysis according to a set of dimensions identified in models of good practice in this area. Our review of ninety-four policies in total revealed several gaps, especially in relation to binding in comparison to nonbinding policies. These are discussed in light of the context of policy-making in the EU, and recommendations are offered for future actions in this area. PMID- 26557653 TI - Effects of Physical (In)activity on Platelet Function. AB - As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality. PMID- 26557656 TI - Modulation Spectra Morphological Parameters: A New Method to Assess Voice Pathologies according to the GRBAS Scale. AB - Disordered voices are frequently assessed by speech pathologists using perceptual evaluations. This might lead to problems caused by the subjective nature of the process and due to the influence of external factors which compromise the quality of the assessment. In order to increase the reliability of the evaluations, the design of automatic evaluation systems is desirable. With that in mind, this paper presents an automatic system which assesses the Grade and Roughness level of the speech according to the GRBAS perceptual scale. Two parameterization methods are used: one based on the classic Mel-Frequency Cepstral Coefficients, which has already been used successfully in previous works, and other derived from modulation spectra. For the latter, a new group of parameters has been proposed, named Modulation Spectra Morphological Parameters: MSC, DRB, LMR, MSH, MSW, CIL, PALA, and RALA. In methodology, PCA and LDA are employed to reduce the dimensionality of feature space, and GMM classifiers to evaluate the ability of the proposed features on distinguishing the different levels. Efficiencies of 81.6% and 84.7% are obtained for Grade and Roughness, respectively, using modulation spectra parameters, while MFCCs performed 80.5% and 77.7%. The obtained results suggest the usefulness of the proposed Modulation Spectra Morphological Parameters for automatic evaluation of Grade and Roughness in the speech. PMID- 26557657 TI - Biology of Heme in Mammalian Erythroid Cells and Related Disorders. AB - Heme is a prosthetic group comprising ferrous iron (Fe(2+)) and protoporphyrin IX and is an essential cofactor in various biological processes such as oxygen transport (hemoglobin) and storage (myoglobin) and electron transfer (respiratory cytochromes) in addition to its role as a structural component of hemoproteins. Heme biosynthesis is induced during erythroid differentiation and is coordinated with the expression of genes involved in globin formation and iron acquisition/transport. However, erythroid and nonerythroid cells exhibit distinct differences in the heme biosynthetic pathway regulation. Defects of heme biosynthesis in developing erythroblasts can have profound medical implications, as represented by sideroblastic anemia. This review will focus on the biology of heme in mammalian erythroid cells, including the heme biosynthetic pathway as well as the regulatory role of heme and human disorders that arise from defective heme synthesis. PMID- 26557658 TI - Hyperacusis Questionnaire as a Tool for Measuring Hypersensitivity to Sound in a Tinnitus Research Population. AB - Hypersensitivity to external sounds is often comorbid with tinnitus and may be significant for adherence to certain types of tinnitus management. Therefore, a clear measure of sensitivity to sound is important. The aim of this study was to evaluate the validity and reliability of the Hyperacusis Questionnaire (HQ) for use as a measurement tool using data from a sample of 264 adults who took part in tinnitus research. We evaluated the HQ factor structure, internal consistency, convergent and discriminant validity, and floor and ceiling effects. Internal consistency was high (Cronbach's alpha = 0.88) and moderate correlations were observed between the HQ, uncomfortable loudness levels, and other health questionnaires. Confirmatory factor analysis revealed that the original HQ three factor solution and a one-factor solution were both a poor fit to the data. Four problematic items were removed and exploratory factor analysis identified a two factor (attentional and social) solution. The original three-factor structure of the HQ was not confirmed. All fourteen items do not accurately assess hypersensitivity to sound in a tinnitus population. We propose a 10-item (2 factor) version of the HQ, which will need to be confirmed using a new tinnitus and perhaps nontinnitus population. PMID- 26557659 TI - Optical Coherence Tomography as a Tool for Ocular Dynamics Estimation. AB - PURPOSE: The aim of the study is to demonstrate that the ocular dynamics of the anterior chamber of the eye can be estimated quantitatively by means of optical coherence tomography (OCT). METHODS: A commercial high speed, high resolution optical coherence tomographer was used. The sequences of tomographic images of the iridocorneal angle of three subjects were captured and each image from the sequence was processed in MATLAB environment in order to detect and identify the contours of the cornea and iris. The data on pulsatile displacements of the cornea and iris and the changes of the depth of the gap between them were retrieved from the sequences. Finally, the spectral analysis of the changes of these parameters was performed. RESULTS: The results of the temporal and spectral analysis manifest the ocular microfluctuation that might be associated with breathing (manifested by 0.25 Hz peak in the power spectra), heart rate (1-1.5 Hz peak), and ocular hemodynamics (3.75-4.5 Hz peak). CONCLUSIONS: This paper shows that the optical coherence tomography can be used as a tool for noninvasive estimation of the ocular dynamics of the anterior segment of the eye, but its usability in diagnostics of the ocular hemodynamics needs further investigations. PMID- 26557660 TI - Analysis of Self-Adhesive Resin Cement Microshear Bond Strength on Leucite Reinforced Glass-Ceramic with/without Pure Silane Primer or Universal Adhesive Surface Treatment. AB - OBJECTIVE: To evaluate the microshear bond strength (MUSBS) of self-adhesive resin (SA) cement on leucite-reinforced glass-ceramic using silane or universal adhesive. MATERIALS AND METHODS: Ceramic blocks were etched with 9.5% hydrofluoric acid and divided into three groups (n = 16): (1) negative control (NC) without treatment; (2) Single Bond Universal (SBU); (3) RelyX Ceramic Primer as positive control (PC). RelyX Unicem resin cement was light-cured, and MUSBS was evaluated with/without thermocycling. The MUSBS was analyzed using one-way analysis of variance. The fractured surfaces were examined using stereomicroscopy and scanning electron microscopy (SEM). RESULTS: Without thermocycling, MUSBS was highest for PC (30.50 MPa +/- 3.40), followed by SBU (27.33 MPa +/- 2.81) and NC (20.18 MPa +/- 2.01) (P < 0.05). Thermocycling significantly reduced MUSBS in SBU (22.49 MPa +/- 4.11) (P < 0.05), but not in NC (20.68 MPa +/- 4.60) and PC (28.77 MPa +/- 3.52) (P > 0.05). PC and NC predominantly fractured by cohesive failure within the ceramic and mixed failure, respectively. CONCLUSION: SBU treatment improves MUSBS between SA cement and glass ceramics, but to a lower value than PC, and the improvement is eradicated by thermocycling. NC exhibited the lowest MUSBS, which remained unchanged after thermocycling. PMID- 26557661 TI - The Association between Job Strain and Atrial Fibrillation: Results from the Swedish WOLF Study. AB - INTRODUCTION: Atrial fibrillation (AF) is a common heart rhythm disorder. Several life-style factors have been identified as risk factors for AF, but less is known about the impact of work-related stress. This study aims to evaluate the association between work-related stress, defined as job strain, and risk of AF. METHODS: Data from the Swedish WOLF study was used, comprising 10,121 working men and women. Job strain was measured by the demand-control model. Information on incident AF was derived from national registers. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and AF risk. RESULTS: In total, 253 incident AF cases were identified during a total follow-up time of 132,387 person years. Job strain was associated with AF risk in a time-dependent manner, with stronger association after 10.7 years of follow-up (HR 1.93, 95% CI 1.10-3.36 after 10.7 years, versus HR 1.11, 95% CI 0.67-1.83 before 10.7 years). The results pointed towards a dose-response relationship when taking accumulated exposure to job strain over time into account. CONCLUSION: This study provides support to the hypothesis that work-related stress defined as job strain is linked to an increased risk of AF. PMID- 26557663 TI - Femtosecond Laser Assisted Deep Anterior Lamellar Keratoplasty Outcomes and Healing Patterns Compared to Manual Technique. AB - The purpose of the study is to report the visual, refractive, and wound healing pattern outcomes of femtosecond assisted deep anterior lamellar keratoplasty (DALK) compared to the conventional manual technique. DALK was performed on 50 eyes of 47 advanced keratoconus patients. The patients were divided into two groups, 25 eyes each, depending on whether femtosecond assisted or manual DALK technique was performed for the side cut of the procedure only. Patients were followed up at 1 month, 6 months, and 1 year for visual acuity, clinical refraction, corneal cylinder, date of suture removal, and side cut corneal healing pattern according to new grading classification of the side cut scar (Grade 0 = transparent scar, 1 = faint healing opacity, 2 = evident healing opacity, 3 = significant opacity with some cosmetic imbalance, and 4 = highly significant opacity with very significant cosmetic imbalance). Outcomes are reported at one year. In conclusion, femtosecond assisted and manual DALK show comparable visual and refractive outcomes but femtosecond assisted DALK shows more evident corneal wound healing patterns at the side cut. This observation may indicate that an activated cornea wound healing might allow earlier suture removal when femtosecond technology is used to perform the side cut for DALK. PMID- 26557662 TI - Cardiovascular Reflexes Activity and Their Interaction during Exercise. AB - Cardiac output and arterial blood pressure increase during dynamic exercise notwithstanding the exercise-induced vasodilation due to functional sympatholysis. These cardiovascular adjustments are regulated in part by neural reflexes which operate to guarantee adequate oxygen supply and by-products washout of the exercising muscles. Moreover, they maintain adequate perfusion of the vital organs and prevent excessive increments in blood pressure. In this review, we briefly summarize neural reflexes operating during dynamic exercise with particular emphasis on their interaction. PMID- 26557664 TI - All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription Independent Mechanism. AB - All-trans retinoic acid (ATRA) has been used as an antineoplastic because of its ability to promote proliferation, inhibition, and differentiation, primarily in leukemia; however, in other types of cancer, such as lung cancer, treatment with ATRA is restricted because not all the patients experience the same results. The ERK signaling pathway is dysregulated in cancer cells, including lung cancer, and this dysregulation promotes proliferation and cell invasion. In this study, we demonstrate that treatment with ATRA can activate the ERK signaling pathway by a transcription-independent mechanism through a signaling cascade that involves RARalpha and PI3K, promoting growth, survival, and migration in lung cancer cells. Until now, this mechanism was unknown in lung cancer cells. The inhibition of the ERK signaling pathway restores the beneficial effects of ATRA, reduces proliferation, increases apoptosis, and blocks the cell migration process in lung cancer cells. In conclusion, our results suggest that the combination of ATRA with ERK inhibitor in clinical trials for lung cancer is warranted. PMID- 26557665 TI - The Context, Process, and Outcome Evaluation Model for Organisational Health Interventions. AB - To facilitate evaluation of complex, organisational health interventions (OHIs), this paper aims at developing a context, process, and outcome (CPO) evaluation model. It builds on previous model developments in the field and advances them by clearly defining and relating generic evaluation categories for OHIs. Context is defined as the underlying frame that influences and is influenced by an OHI. It is further differentiated into the omnibus and discrete contexts. Process is differentiated into the implementation process, as the time-limited enactment of the original intervention plan, and the change process of individual and collective dynamics triggered by the implementation process. These processes lead to proximate, intermediate, and distal outcomes, as all results of the change process that are meaningful for various stakeholders. Research questions that might guide the evaluation of an OHI according to the CPO categories and a list of concrete themes/indicators and methods/sources applied within the evaluation of an OHI project at a hospital in Switzerland illustrate the model's applicability in structuring evaluations of complex OHIs. In conclusion, the model supplies a common language and a shared mental model for improving communication between researchers and company members and will improve the comparability and aggregation of evaluation study results. PMID- 26557666 TI - The Ethanolic Extract of Taiwanofungus camphoratus (Antrodia camphorata) Induces Cell Cycle Arrest and Enhances Cytotoxicity of Cisplatin and Doxorubicin on Human Hepatocellular Carcinoma Cells. AB - Taiwanofungus camphoratus (synonym Antrodia camphorata) is a widely used medicinal fungus in the folk medicine of Taiwan with several pharmacological features such as anti-inflammatory, liver protection, antihypertensive, and antioxidative activities. The ethanolic extract of T. camphoratus (TCEE) which contains abundant bioactive compounds including triterpenoids and polysaccharides also has antitumor effects in various human cancer cell lines. The aims of this study are to clarify the antitumor effects of TCEE on human hepatocellular carcinoma cells and also evaluate the combination drug effects with conventional chemotherapy agents, cisplatin and doxorubicin. In the present study, the TCEE treatment induced cell cycle arrest and suppressed cell growth on both Hep3B and HepJ5 cells. Expression of cell cycle inhibitors, P21 and P27, and activation of apoptosis executer enzyme, caspase-3, were also induced by TCEE. In combination with the chemotherapy agents, TCEE treatment further enhanced the tumor suppression efficiency of cisplatin and doxorubicin. These results together suggested that TCEE is a potential ingredient for developing an integrated chemotherapy for human liver cancer. PMID- 26557667 TI - Evaluation of the Effect of Hypercapnia on Vascular Function in Normal Tension Glaucoma. AB - INTRODUCTION: Altered ocular perfusion and vascular dysregulation have been reported in glaucoma. The aim of this paper was to evaluate the vascular response to a hypercapnic stimulus. METHODS: Twenty normal tension glaucoma (NTG) patients and eighteen age- and gender-matched controls had pulsatile ocular blood flow (POBF) measurements, systemic cardiovascular assessment, and laser Doppler digital blood flow (DBF) assessed. Measurements were taken at baseline, after 10 minutes rest, in the stable sitting and supine positions and following induction and stabilization of hypercapnia, which induced a 15% increase in end-tidal pCO2. The POBF response to hypercapnia was divided into high (>20%) and low responders (<20%). RESULTS: 65% of NTG patients had a greater than 41% increase in POBF following CO2 rebreathing (high responders). These high responders had a lower baseline POBF, lower baseline DBF, and a greater DBF response to thermal stimulus. CONCLUSION: NTG patients that have a greater than 20% increase in POBF after a hypercapnic stimulus have lower baseline POBF and DBF values. This suggests that there is impaired regulation of blood flow in a significant subgroup of NTG patients. This observation may reflect a generalised dysfunction of the vascular endothelium. PMID- 26557668 TI - Is It Time to Beta Block the Septic Patient? AB - Beta blockers are some of the most studied drugs in the pharmacopoeia. They are already widely used in medicine for treating hypertension, chronic heart failure, tachyarrhythmias, and tremor. Whilst their use in the immediate perioperative patient has been questioned, the use of esmolol in the patients with established septic shock has been recently reported to have favourable outcomes. In this paper, we review the role of the adrenergic system in sepsis and the evidence for the use of beta stimulation and beta blockers from animal models to critically ill patients. PMID- 26557669 TI - The Role of Systemic Arterial Stiffness in Open-Angle Glaucoma with Diabetes Mellitus. AB - PURPOSE: To investigate the role of systemic arterial stiffness in glaucoma patients with diabetes mellitus (DM). DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: DM subjects who underwent brachial-ankle pulse wave velocity (baPWV) were recruited. METHODS: Glaucoma patients (n = 75) and age-matched control subjects (n = 92) were enrolled. Systemic examination including BaPWV and detailed eye examination were performed. The glaucoma group was divided into subgroups of normal tension glaucoma (NTG, n = 55) and primary open-angle glaucoma (POAG) based on an IOP of 21 mmHg. BaPWV was used to stratify the population into 4 groups based on the rate. Stepwise multiple logistic regression analysis by baPWV quartiles was used to compare the glaucoma group with the control group. MAIN OUTCOME MEASURES: BaPWV in glaucoma with DM patients. RESULTS: Faster baPWV was positively associated with glaucoma (odds ratio: 3.74; 95% CI: 1.03-13.56, stepwise multiple logistic regression analysis) in patients with DM. Increasing baPWV was also positively associated with glaucoma (p for trend = 0.036). The NTG subgroup showed similar results to those of the glaucoma group. CONCLUSIONS: In this study, increased arterial stiffness was shown to be associated with glaucoma and may contribute to the pathogenesis of glaucoma in DM patients. PMID- 26557670 TI - Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males. AB - There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD). Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA) axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females) with burnout on sickness absence and 40 healthy participants (16 males and 24 females) were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha amylase) were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis. PMID- 26557671 TI - Comparison of Ocular Pulse Amplitude Lowering Effects of Preservative-Free Tafluprost and Preservative-Free Dorzolamide-Timolol Fixed Combination Eyedrops. AB - PURPOSE: To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry. METHODS: In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment. RESULTS: After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01). CONCLUSIONS: Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP. PMID- 26557672 TI - Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells. AB - Flow cytometric test for analyzing the eosin-5-maleimide (EMA) binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS). However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP) and Southeast Asian ovalocytosis (SAO), which are forms in the category of hereditary elliptocytosis (HE), show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF) cut-off value of 36.4 (sensitivity 0.97, specificity 0.95). Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells. PMID- 26557673 TI - Ocular Surface and Tear Film Changes in Older Women Working with Computers. AB - The aim of this work is to investigate changes in the ocular surface (OS) and tear film (TF) by means of questionnaire-based subjective symptoms, TF break-up time, Schirmer test, and TF analysis in women working with computers and to analyze the effects of the oral supplementation with antioxidants/omega 3 fatty acids (A/omega3) in the OS outcomes. Women aged 40-65 years (n = 148) were recruited at the Administrative Offices of Valencia (Spain) and distributed into two age groups, 40-52 years (AGE1; n = 87) and 53-65 years (AGE2; n = 61), and then subdivided according to being (or not) computer users (CUG; NCUG) during the workday. Homogeneous subgroups were randomly assigned (or not) to the daily intake of three pills of A/omega3 for three months. At baseline and at the end of follow-up, personalized interviews and ocular examination were done. Reflex tear samples were collected from the inferior meniscus and processed for a multiplexed particle-based flow cytometry assay to measure proinflammatory molecules. Statistics were performed using the SPSS 15.0 program. The OS pathology was clinically evident in the AGE1-CUG (33%) versus the AGE2-CUG (64%) of women. Significantly higher interleukins-1beta and -6 tear levels were found in the AGE1 versus the AGE2 women employees (P = 0.006 and P = 0.001, resp.), as well as in the CUG versus the NCUG (P = 0.001 and P = 0.000, resp.). Supplementation with A/omega3 positively influenced the OS pathology as manifested by the amelioration of the clinical signs/symptoms related to computer uses. Strategies involving a safe environment and oral micronutrient supplements may be managed within eye care standards in older women. PMID- 26557674 TI - Ocular Manifestations of Ebola Virus Disease: An Ophthalmologist's Guide to Prevent Infection and Panic. AB - Ebola virus disease (EVD--formerly known as Ebola hemorrhagic fever) is a severe hemorrhagic fever caused by lipid-enveloped, nonsegmented, negative-stranded RNA viruses belonging to the genus Ebolavirus. Case fatality rates may reach up to 76% of infected individuals, making this infection a deadly health problem in the sub-Saharan population. At the moment, there are still no indications on ophthalmological clinical signs and security suggestions for healthcare professionals (doctors and nurses or cooperative persons). This paper provides a short but complete guide to reduce infection risks. PMID- 26557675 TI - HPTLC Analysis of Bioactivity Guided Anticancer Enriched Fraction of Hydroalcoholic Extract of Picrorhiza kurroa. AB - OBJECTIVE: Hydroalcoholic extract of Picrorhiza kurroa and its fractions were subjected to in vitro screening for cytotoxicity; further best active fraction (BAF) obtained was tested against Ehrlich ascites carcinoma (EAC) model in Balb/c mice after its quality control analysis. METHODS: Cytotoxicities of all the fractions and mother extract of P. kurroa were determined, using MTT assay on breast cancer (MCF-7, MDA-MB 231) and cervical cancer (HeLa, SiHa) cell lines. Metabolic fingerprinting was developed using HPTLC with quantification of biomarkers (cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin) in BAF. The EAC tumor-bearing mice were used for in vivo anticancer activity after oral administration (50 mg Kg(-1)) for 10 days. RESULTS: Cytotoxicity assay of mother extract and its fractions over breast cancer and cervix cancer cell lines showed that dichloromethane (DCM) fraction was most cytotoxic (IC50 36.0-51.0 ug mL(-1) at 72 h). Oral administration of DCM fraction showed significant reduction in tumor regression parameters, viable tumor cell count and restoration of hematological parameters may be due to presence of cucurbitacins B and E; betulinic acid; picrosides 1 and 2; and apocynin, as compared to the untreated mice of the control group. CONCLUSION: The DCM fraction of P. kurroa displayed potent anticancer activity and can be further explored for the development of a potential candidate for cancer therapy. PMID- 26557676 TI - Basic Competence of Intensive Care Unit Nurses: Cross-Sectional Survey Study. AB - Critical care patients benefit from the attention of nursing personnel with a high competence level. The aim of the study was to describe and evaluate the self assessed basic competence of intensive care unit nurses and related factors. A cross-sectional survey design was used. A basic competence scale (Intensive and Critical Care Nursing Competence Scale version 1, Likert scale 1-5, 1 = poor and 5 = excellent) was employed among Finnish intensive care unit nurses (n = 431). Intensive care unit nurses' self-assessed basic competence was good (mean 4.19, SD 0.40). The attitude and value base of basic competence was excellent whereas experience base was the poorest compared to the knowledge base and skill base of intensive and critical care nursing. The strongest factor explaining nurses' basic competence was their experience of autonomy in nursing care (F value 60.85, beta 0.11, SE 0.01, and P <= 0.0001). Clinical competence was self-rated as good. Nurses gave their highest competence self-ratings for ICU patient care according to the principles of nursing care. The ICU nurses also self-rated their professional competence as good. Collaboration was self-rated as the best competence. In basic and continuing education and professional self-development discussions it is meaningful to consider and find solutions for how to improve nurses' experienced autonomy in nursing. PMID- 26557678 TI - Prognostic Factors of Returning to Work after Sick Leave due to Work-Related Common Mental Disorders: A One- and Three-Year Follow-Up Study. AB - The aim of this paper was to assess the prognostic factors of return to work (RTW) after one and three years among people on sick leave due to occupational stress. Methods. The study population comprised 223 completers on sick leave, who participated in a stress treatment program. Self-reported psychosocial work environment, life events during the past year, severity of the condition, occupational position, employment sector, marital status, and medication were assessed at baseline. RTW was assessed with data from a national compensation database (DREAM). Results. Self-reported high demands, low decision authority, low reward, low support from leaders and colleagues, bullying, high global symptom index, length of sick leave at baseline, and stressful negative life events during the year before baseline were associated with no RTW after one year. Low work ability and full-time sick leave at inclusion were predictors after three years too. Being single was associated with no RTW after three years. The type of treatment, occupational position, gender, age, and degree of depression were not associated with RTW after one or three years. Conclusion. The impact of the psychosocial work environment as predictor for RTW disappeared over time and only the severity of the condition was a predictor for RTW in the long run. PMID- 26557677 TI - Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children? AB - OBJECTIVE: To evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. METHODS: This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. RESULTS: Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2%) had bilateral responses. Four (9.5%) showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7%) in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. CONCLUSION: ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses. PMID- 26557679 TI - Prevalence and Risk Factors of Prostate Cancer in Chinese Men with PSA 4-10 ng/mL Who Underwent TRUS-Guided Prostate Biopsy: The Utilization of PAMD Score. AB - PURPOSE: To elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4-10 ng/mL and develop a risk-stratification score model. METHODS: The data of 345 patients who underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volume (PV), magnetic resonance imaging (MRI), and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason Score >= 7). RESULTS: The median PSA was 7.15 (IQR 5.91-8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results, and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a "PAMD" score which combined the four factors to categorize patients into three risk groups, and the model performed good predictive sensitivity and specificity. CONCLUSION: The prevalence of prostate cancer in Chinese patients with PSA 4-10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI, and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk stratification and decision-making. PMID- 26557680 TI - Electrical Bioimpedance Spectroscopy on Acute Unilateral Stroke Patients: Initial Observations regarding Differences between Sides. AB - PURPOSE: Electrical Bioimpedance Cerebral Monitoring is assessment in real time of health of brain tissue through study of passive dielectric properties of brain. During the last two decades theory and technology have been developed in parallel with animal experiments aiming to confirm feasibility of using bioimpedance-based technology for prompt detection of brain damage. Here, for the first time, we show that electrical bioimpedance measurements for left and right hemispheres are significantly different in acute cases of unilateral stroke within 24 hours from onset. METHODS: Electrical BIS measurements have been taken in healthy volunteers and patients suffering from acute stroke within 24 hours of onset. BIS measurements have been obtained using SFB7 bioimpedance spectrometer manufactured by Impedimed ltd. and 4-electrode method. Measurement electrodes, current, and voltage have been placed according to 10-20 EEG system obtaining mutual BIS measurements from 4 different channels situated in pairs symmetrically from the midsagittal line. Obtained BIS data has been analyzed, assessing for symmetries and differences regarding healthy control data. RESULTS: 7 out of 10 patients for Side-2-Side comparisons and 8 out 10 for central/lateral comparison presented values outside the range defined by healthy control group. When combined only 1 of 10 patients exhibited values within the healthy range. CONCLUSIONS: If these initial observations are confirmed with more patients, we can foresee emerging of noninvasive monitoring technology for brain damage with the potential to lead to paradigm shift in treatment of brain stroke and traumatic brain damage. PMID- 26557681 TI - Effects of Computer-Aided Manufacturing Technology on Precision of Clinical Metal Free Restorations. AB - PURPOSE: The purpose of this study was to investigate the marginal fit of metal free crowns made by three different computer-aided design/computer-aided manufacturing (CAD/CAM) systems. MATERIALS AND METHODS: The maxillary left first premolar of a dentiform was prepared for all-ceramic crown restoration. Thirty all-ceramic premolar crowns were made, ten each manufactured by the Lava system, Cercon, and Cerec. Ten metal ceramic gold (MCG) crowns served as control. The marginal gap of each sample was measured under a stereoscopic microscope at 75x magnification after cementation. One-way ANOVA and the Duncan's post hoc test were used for data analysis at the significance level of 0.05. RESULTS: The mean (standard deviation) marginal gaps were 70.5 (34.4) MUm for the MCG crowns, 87.2 (22.8) MUm for Lava, 58.5 (17.6) MUm for Cercon, and 72.3 (30.8) MUm for Cerec. There were no significant differences in the marginal fit among the groups except that the Cercon crowns had significantly smaller marginal gaps than the Lava crowns (P < 0.001). CONCLUSIONS: Within the limitation of this study, all the metal-free restorations made by the digital CAD/CAM systems had clinically acceptable marginal accuracy. PMID- 26557682 TI - Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells. AB - Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin. PMID- 26557683 TI - Origins of the Vertebrate Erythro/Megakaryocytic System. AB - Vertebrate erythrocytes and thrombocytes arise from the common bipotent thrombocytic-erythroid progenitors (TEPs). Even though nonmammalian erythrocytes and thrombocytes are phenotypically very similar to each other, mammalian species have developed some key evolutionary improvements in the process of erythroid and thrombocytic differentiation, such as erythroid enucleation, megakaryocyte endoreduplication, and platelet formation. This brings up a few questions that we try to address in this review. Specifically, we describe the ontology of erythro thrombopoiesis during adult hematopoiesis with focus on the phylogenetic origin of mammalian erythrocytes and thrombocytes (also termed platelets). Although the evolutionary relationship between mammalian and nonmammalian erythroid cells is clear, the appearance of mammalian megakaryocytes is less so. Here, we discuss recent data indicating that nonmammalian thrombocytes and megakaryocytes are homologs. Finally, we hypothesize that erythroid and thrombocytic differentiation evolved from a single ancestral lineage, which would explain the striking similarities between these cells. PMID- 26557684 TI - Analysis of Retinal Peripapillary Segmentation in Early Alzheimer's Disease Patients. AB - Decreased thickness of the retinal nerve fiber layer (RNFL) may reflect retinal neuronal-ganglion cell death. A decrease in the RNFL has been demonstrated in Alzheimer's disease (AD) in addition to aging by optical coherence tomography (OCT). Twenty-three mild-AD patients and 28 age-matched control subjects with mean Mini-Mental State Examination 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision, were considered for study. OCT peripapillary and macular segmentation thickness were examined in the right eye of each patient. Compared to controls, eyes of patients with mild-AD patients showed no statistical difference in peripapillary RNFL thickness (P > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, while in sectors 1, 5, 6, 7, and 10 there was thickening. Total macular volume and RNFL thickness of the fovea in all four inner quadrants and in the outer temporal quadrants proved to be significantly decreased (P < 0.01). Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild-AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage. PMID- 26557685 TI - Physicochemical Aspects of the Plasmodium chabaudi-Infected Erythrocyte. AB - Membrane electrochemical potential is a feature of the molecular profile of the cell membrane and the two-dimensional arrangement of its charge-bearing molecules. Plasmodium species, the causative agents of malaria, are intracellular parasites that remodel host erythrocytes by expressing their own proteins on erythrocyte membranes. Although various aspects of the modifications made to the host erythrocyte membrane have been extensively studied in some human Plasmodium species (such as Plasmodium falciparum), details of the structural and molecular biological modifications made to host erythrocytes by nonhuman Plasmodium parasites have not been studied. We employed zeta potential analysis of erythrocytes parasitized by P. chabaudi, a nonhuman Plasmodium parasite. From these measurements, we found that the surface potential shift was more negative for P. chabaudi-infected erythrocytes than for P. falciparum-infected erythrocytes. However, electron microscopic analysis of the surface of P. chabaudi-infected erythrocytes did not reveal any modifications as compared with nonparasitized erythrocytes. These results suggest that differences in the membrane modifications found herein represent unique attributes related to the pathogenesis profiles of the two different malaria parasite species in different host animals and that these features have been acquired through parasite adaptations acquired over long evolutionary time periods. PMID- 26557686 TI - Associations between Distal Upper Extremity Job Physical Factors and Psychosocial Measures in a Pooled Study. AB - INTRODUCTION: There is an increasing body of literature relating musculoskeletal diseases to both job physical exposures and psychosocial outcomes. Relationships between job physical exposure measures and psychosocial factors have not been well examined or quantified. These exploratory analyses evaluate relationships between quantified exposures and psychosocial outcomes. METHODS: Individualized quantification of duration, repetition, and force and composite scores of the Strain Index (SI) and the Threshold Limit Value for Hand Activity Level (TLV for HAL) were compared to 10 psychosocial measures. Relationships and predicted probabilities were assessed using ordered logistic regression. Analyses were adjusted for age, BMI, and gender. RESULTS AND DISCUSSION: Among 1834 study participants there were multiple statistically significant relationships. In general, as duration, repetition, and force increased, psychosocial factors worsened. However, general health and mental exhaustion improved with increasing job exposures. Depression was most strongly associated with increased repetition, while physical exhaustion was most strongly associated with increased force. SI and TLV for HAL were significantly related to multiple psychosocial factors. These relationships persisted after adjustment for strong confounders. CONCLUSION: This study quantified multiple associations between job physical exposures and occupational and nonoccupational psychosocial factors. Further research is needed to quantify the impacts on occupational health outcomes. PMID- 26557687 TI - Consequences of Job Insecurity on the Psychological and Physical Health of Greek Civil Servants. AB - The aim of this study was to estimate the short term consequences of job insecurity associated with a newly introduced mobility framework in Greece. In specific, the study examined the impact of job insecurity on anxiety, depression, and psychosomatic and musculoskeletal symptoms, two months after the announcement of the mobility framework. In addition the study also examined the "spill over" effects of job insecurity on employees not directly affected by the mobility framework. Personal interviews using a structured questionnaire were conducted for 36 university administrative employees awaiting repositioning, 36 coworkers not at risk, and 28 administrative employees of a local hospital not at risk. Compared to both control groups the employees in the anticipation phase of labor mobility had significantly worse scores for perceived stress, anxiety, depression, positive affect, negative affect, social support, marital discord, common somatic symptoms, and frequency of musculoskeletal pain. This study highlights the immediate detrimental effects of job insecurity on the physical, psychological, and social functioning of employees. There is a need for the development of front line interventions to prevent these effects from developing into chronic conditions with considerable cost for the individual and society in general. PMID- 26557688 TI - Nonword Repetition and Speech Motor Control in Children. AB - This study examined how familiarity of word structures influenced articulatory control in children and adolescents during repetition of real words (RWs) and nonwords (NWs). A passive reflective marker system was used to track articulator movement. Measures of accuracy were obtained during repetition of RWs and NWs, and kinematic analysis of movement duration and variability was conducted. Participants showed greater consonant and vowel accuracy during RW than NW repetition. Jaw movement duration was longer in NWs compared to RWs across age groups, and younger children produced utterances with longer jaw movement duration compared to older children. Jaw movement variability was consistently greater during repetition of NWs than RWs in both groups of participants. The results indicate that increases in phonological short-term memory demands affect articulator movement. This effect is most pronounced in younger children. A range of skills may develop during childhood, which supports NW repetition skills. PMID- 26557689 TI - Reproducibility of Neonate Ocular Circulation Measurements Using Laser Speckle Flowgraphy. AB - Measuring the ocular blood flow in neonates may clarify the relationships between eye diseases and ocular circulation abnormalities. However, no method for noninvasively measuring ocular circulation in neonates is established. We used laser speckle flowgraphy (LSFG) modified for neonates to measure their ocular circulation and investigated whether this method is reproducible. During their normal sleep, we studied 16 subjects (adjusted age of 34-48 weeks) whose blood flow could be measured three consecutive times. While the subjects slept in the supine position, three mean blur rate (MBR) values of the optic nerve head (ONH) were obtained: the MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean), and nine blood flow pulse waveform parameters in the ONH were examined. We analyzed the coefficient of variation (COV) and the intraclass correlation coefficient (ICC) for each parameter. The COVs of the MBR values were all <= 10%. The ICCs of the MBR values were all >0.8. Good COVs were observed for the blowout score, blowout time, rising rate, falling rate, and acceleration time index. Although the measurement of ocular circulation in the neonates was difficult, our results exhibited reproducibility, suggesting that this method could be used in clinical research. PMID- 26557690 TI - Acoustic Correlates of Compensatory Adjustments to the Glottic and Supraglottic Structures in Patients with Unilateral Vocal Fold Paralysis. AB - The goal of this study was to analyse perceptually and acoustically the voices of patients with Unilateral Vocal Fold Paralysis (UVFP) and compare them to the voices of normal subjects. These voices were analysed perceptually with the GRBAS scale and acoustically using the following parameters: mean fundamental frequency (F0), standard-deviation of F0, jitter (ppq5), shimmer (apq11), mean harmonics-to noise ratio (HNR), mean first (F1) and second (F2) formants frequency, and standard-deviation of F1 and F2 frequencies. Statistically significant differences were found in all of the perceptual parameters. Also the jitter, shimmer, HNR, standard-deviation of F0, and standard-deviation of the frequency of F2 were statistically different between groups, for both genders. In the male data differences were also found in F1 and F2 frequencies values and in the standard-deviation of the frequency of F1. This study allowed the documentation of the alterations resulting from UVFP and addressed the exploration of parameters with limited information for this pathology. PMID- 26557691 TI - PLK-1 Targeted Inhibitors and Their Potential against Tumorigenesis. AB - Mitotic kinases are the key components of the cell cycle machinery and play vital roles in cell cycle progression. PLK-1 (Polo-like kinase-1) is a crucial mitotic protein kinase that plays an essential role in both the onset of G2/M transition and cytokinesis. The overexpression of PLK-1 is strongly correlated with a wide spectrum of human cancers and poor prognosis. The (si)RNA-mediated depletion of PLK-1 arrests tumor growth and triggers apoptosis in cancer cells without affecting normal cells. Therefore, PLK-1 has been selected as an attractive anticancer therapeutic drug target. Some small molecules have been discovered to target the catalytic and noncatalytic domains of PLK-1. These domains regulate the catalytic activation and subcellular localization of PLK-1. However, while PLK-1 inhibitors block tumor growth, they have been shown to cause severe adverse complications, such as toxicity, neutropenia, and bone marrow suppression during clinical trials, due to a lack of selectivity and specificity within the human kinome. To minimize these toxicities, inhibitors should be tested against all protein kinases in vivo and in vitro to enhance selectivity and specificity against targets. Here, we discuss the potency and selectivity of PLK-1-targeted inhibitors and their molecular interactions with PLK-1 domains. PMID- 26557693 TI - Workplace Bullying as a Risk Factor for Musculoskeletal Disorders: The Mediating Role of Job-Related Psychological Strain. AB - Workplace bullying is considered by the European Agency for Safety and Health at Work one of the emerging psychosocial risk factors that could negatively affect workers' health. Thus, the aim of this study was to analyze the process that leads from bullying to negative health (such as musculoskeletal disorders (MSDs)), testing the mediating role of job-related strain. Data were collected on 512 workers (62.9% female; mean age = 43.6 years) of a retail chain who filled in a self-report questionnaire after a one-hour training session on work-related stress. Data analyses were performed controlling for potentially confounding variables (i.e., gender, age, organizational role, type of contract, and perceived physical job demands). Preacher and Hayes analytical approach was used to test the indirect relationship between bullying and MSDs. Results showed that work-related strain mediates the relationship between bullying and MSDs considered (low back, upper back, and neck) except for MSDs of the shoulders. Our study confirms the role played by bullying and job-related strain in determining workers' MSDs. PMID- 26557692 TI - Estimating the Impact of Workplace Bullying: Humanistic and Economic Burden among Workers with Chronic Medical Conditions. AB - BACKGROUND: Although the prevalence of work-limiting diseases is increasing, the interplay between occupational exposures and chronic medical conditions remains largely uncharacterized. Research has shown the detrimental effects of workplace bullying but very little is known about the humanistic and productivity cost in victims with chronic illnesses. We sought to assess work productivity losses and health disutility associated with bullying among subjects with chronic medical conditions. METHODS: Participants (N = 1717) with chronic diseases answered a self-administered survey including sociodemographic and clinical data, workplace bullying experience, the SF-12 questionnaire, and the Work Productivity Activity Impairment questionnaire. RESULTS: The prevalence of significant impairment was higher among victims of workplace bullying as compared to nonvictims (SF-12 PCS: 55.5% versus 67.9%, p < 0.01; SF-12 MCS: 59.4% versus 74.3%, p < 0.01). The adjusted marginal overall productivity cost of workplace bullying ranged from 13.9% to 17.4%, corresponding to Italian Purchase Power Parity (PPP) 2010 US$ 4182-5236 yearly. Association estimates were independent and not moderated by concurrent medical conditions. CONCLUSIONS: Our findings demonstrate that the burden on workers' quality of life and productivity associated with workplace bullying is substantial. This study provides key data to inform policy-making and prioritize occupational health interventions. PMID- 26557694 TI - The Changes of Retinal Saturation after Long-Term Tamponade with Silicone Oil. AB - PURPOSE: To evaluate the effects of long-term tamponade with silicone oil on retinal saturation. METHODS: A total of 49 eyes that received tamponade with silicone oil were included. The patients were divided into 3 groups (3-6 months, 6-9 months, and >9 months) according to the duration of silicone oil tamponade. Retinal oximetry was performed using the Oxymap system before and 2 months after silicone oil removal. RESULTS: The mean retinal oxygen saturation before silicone oil removal was 107% +/- 12% in the arterioles and 60% +/- 10% in the venules, with an overall arteriovenous difference (AVD) of 47% +/- 14%. The AVD in the >9 month group was significantly higher than that in the 3-6-month group (54% +/- 16% versus 44% +/- 11%, P = 0.042). After silicone oil removal, the AVD in the >9 month group was significantly decreased (45% +/- 9% versus 54% +/- 16%, P = 0.009); additionally, the arterioles were significantly wider than before surgery (10.8 +/- 0.7 pixels versus 10.4 +/- 0.9 pixels, P = 0.015). CONCLUSIONS: The tamponade with silicone oil for more than 9 months will cause the alterations of retinal saturation and the narrowing of retinal arterioles, which may further interfere with the oxygen metabolism in the retina. PMID- 26557695 TI - Diverse of Erythropoiesis Responding to Hypoxia and Low Environmental Temperature in Vertebrates. AB - Erythrocytes are responsible for transporting oxygen to tissue and are essential for the survival of almost all vertebrate animals. Circulating erythrocyte counts are tightly regulated and respond to erythrocyte mass and oxygen tension. Since the discovery of erythropoietin, the erythropoietic responses to environment and tissue oxygen tension have been investigated in mice and human. Moreover, it has recently become increasingly clear that various environmental stresses could induce the erythropoiesis via various modulating systems, while all vertebrates live in various environments and habitually adapt to environmental stress. Therefore, it is considered that investigations of erythropoiesis in vertebrates provide a lead to the various erythropoietic responses to environmental stress. This paper comparatively introduces the present understanding of erythropoiesis in vertebrates. Indeed, there is a wide range of variations in vertebrates' erythropoiesis. This paper also focused on erythropoietic responses to environmental stress, hypoxia, and lowered temperature in vertebrates. PMID- 26557696 TI - Stem Cell Therapy in Injured Vocal Folds: A Three-Month Xenograft Analysis of Human Embryonic Stem Cells. AB - We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (p <= 0.011). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (p <= 0.031). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives. PMID- 26557697 TI - Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation. AB - H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion. PMID- 26557698 TI - Antiproliferative Activity of T. welwitschii Extract on Jurkat T Cells In Vitro. AB - Triumfetta welwitschii is a plant used traditionally for the treatment of fever and diarrhoea. Previous work has shown that T. welwitschii has antibacterial activity. The purpose of this study was to investigate T. welwitschii extract for anticancer activity against Jurkat T cells. The Jurkat T cell line is used to study acute T cell leukaemia. An antiproliferation assay, determination of induction of apoptosis, the determination of the effect of the combination of the extract and GSH, and effects of the extract on DNA leakage were conducted. T. welwitschii was found to decrease cell viability in a dose- and time-dependent manner. T. welwitschii caused apoptosis in the Jurkat T cells as shown by DNA fragmentation. When T. welwitschii was combined with reduced GSH, it was found that the growth of the Jurkat T cells was significantly reduced compared to untreated cells after 72 h of treatment. This was unexpected, as cancer cells have elevated levels of GSH compared to normal cells. The results of this study show that T. welwitschii is a potential source of compounds that may serve as leads for anticancer compounds. PMID- 26557699 TI - Job Strain and Self-Reported Insomnia Symptoms among Nurses: What about the Influence of Emotional Demands and Social Support? AB - Job strain, derived from high psychological demands and low job control, is associated with insomnia, but information on the role of emotional demands and social support in this relationship is scarce. The aims of this study were (i) to test the association between job strain and self-reported insomnia symptoms, (ii) to evaluate the combination of emotional demands and job control regarding insomnia symptoms, and (iii) to analyze the influence of social support in these relationships. This cross-sectional study refers to a sample of nurses (N = 3,013 and N = 3,035 for Job Strain and Emotional demand-control model, resp.) working at public hospitals in Rio de Janeiro, Brazil. Data were collected through a self report questionnaire. The prevalence of insomnia symptoms was 34.3%. Job strain was associated with increased odds for insomnia symptoms (OR: 2.20); the same result was observed with the combination of emotional demands and low job control (OR: 1.99). In both models, the inclusion of low social support combined with high demands and low job control led to increased odds for insomnia symptoms, compared to groups with high social support from coworkers and supervisors. Besides job strain, the study of emotional demands and social support are promising with regards to insomnia symptoms, particularly among nurses. PMID- 26557700 TI - Treatment of Hemorrhagic Vocal Polyps by Pulsed Dye Laser-Assisted Laryngomicrosurgery. AB - OBJECTIVE: Conventional surgical techniques of laryngomicrosurgery (LMS) on hemorrhagic vocal polyps are often difficult due to obscuration of the surgical field by inadvertent bleeding from the lesion, and there are often significant amounts of mucosal epithelium loss. Here, we introduce our surgical technique using pulsed dye laser (PDL), which can effectively resect the polyp with vocal fold mucosa preservation. METHODS: Patients who were diagnosed with hemorrhagic vocal polyp and who were surgically managed using PDL from March 2013 to October 2014 were retrospectively reviewed. Preoperative and postoperative clinical outcomes and surgical findings were evaluated. RESULTS: A total of 39 patients were treated with PDL-assisted enucleation LMS. The average age was 43.7 years (range 20-73), and there were 20 males and 19 females (17 professional voice users). In all cases, the hemorrhagic polyp was successfully enucleated after application of PDL, thereby preserving the overlying epithelium. Postoperative voice outcomes were favorable with clear preservation of the vocal fold mucosal wave. CONCLUSION: PDL-assisted enucleation LMS for the treatment of hemorrhagic vocal polyps can be a safe and effective surgical technique. It can be considered a promising treatment option for hemorrhagic vocal polyps. PMID- 26557701 TI - Over-the-Counter Hearing Aids: A Lost Decade for Change. AB - BACKGROUND: Hearing aids sold directly to consumers in retail stores or through the internet, without individual prescription by audiological professionals, are termed over-the-counter (OTC) devices. This study aimed to determine whether there was any change in the electroacoustic characteristics of OTC devices compared to research carried out a decade earlier. The previous results indicated that most OTC devices were low-frequency-emphasis devices and were unsuitable for elderly people with presbycusis, who were likely to be the major consumers of these products. METHODS: Ten OTC devices were selected and their electroacoustic performance was measured. Appropriate clients for the OTC devices were derived, using four linear prescription formulae, and OTC suitability for elderly persons with presbycusis was investigated. RESULTS: OTC electroacoustic characteristics were similar to those in the earlier study. Most OTC devices were not acoustically appropriate for potential consumers with presbycusis. Although several of the devices could match prescriptive targets for individuals with presbycusis, their poor electroacoustic performance--including ineffective volume control function, high equivalent input noise, and irregular frequency response- may override their potential benefit. CONCLUSION: The low-cost OTC devices were generally not suitable for the main consumers of these products, and there has been little improvement in the appropriateness of these devices over the past decade. PMID- 26557702 TI - The Association between Primary Open-Angle Glaucoma and Blood Pressure: Two Aspects of Hypertension and Hypotension. AB - Glaucoma is the second leading cause of blindness worldwide. Although the mechanism of the development of primary open-angle glaucoma (POAG) is not fully understood, elevated intraocular pressure (IOP) is considered the most important risk factor. Several vascular factors have also been identified as risk factors and can lead to hypoperfusion of the optic nerve head and thus may play an important role in the pathogenesis and progression of POAG. The results of the present study suggest that both high and low blood pressure (BP) are associated with an increased risk of POAG based on a comprehensive literature review. Elevated BP is associated with elevated IOP, leading to increased risk of glaucoma, but excessive BP lowering in glaucoma patients may cause a drop in ocular perfusion pressure (OPP) and subsequent ischemic injury. The relationship between IOP, OPP, and BP suggests that the relationship between BP and glaucoma progression is U-shaped. PMID- 26557703 TI - Effects of a Workplace Intervention Targeting Psychosocial Risk Factors on Safety and Health Outcomes. AB - The goal of this study was to test the effectiveness of a workplace intervention targeting work-life stress and safety-related psychosocial risk factors on health and safety outcomes. Data were collected over time using a randomized control trial design with 264 construction workers employed in an urban municipal department. The intervention involved family- and safety-supportive supervisor behavior training (computer-based), followed by two weeks of behavior tracking and a four-hour, facilitated team effectiveness session including supervisors and employees. A significant positive intervention effect was found for an objective measure of blood pressure at the 12-month follow-up. However, no significant intervention results were found for self-reported general health, safety participation, or safety compliance. These findings suggest that an intervention focused on supervisor support training and a team effectiveness process for planning and problem solving should be further refined and utilized in order to improve employee health with additional research on the beneficial effects on worker safety. PMID- 26557704 TI - Antiproliferative and Antiestrogenic Activities of Bonediol an Alkyl Catechol from Bonellia macrocarpa. AB - The purpose of this study was to investigate antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plant Bonellia macrocarpa. Bonediol was assessed for growth inhibition of androgen-sensitive (LNCaP), androgen-insensitive (PC-3), and metastatic androgen-insensitive (PC-3M) human prostate tumor cells; toxicity on normal cell line (HEK 293) was also evaluated. Hedgehog pathway was evaluated and competitive 3H-estradiol ligand binding assay was performed. Additionally, antioxidant activity on Nrf2-ARE pathway was evaluated. Bonediol induced a growth inhibition on prostate cancer cell lines (IC50 from 8.5 to 20.6 uM). Interestingly, bonediol binds to both estrogen receptors (ERalpha (2.5 uM) and ERbeta (2.1 uM)) and displaces the native ligand E2 (17beta-estradiol). No significant activity was found in the Hedgehog pathway. Additionally, activity of bonediol on Nrf2-ARE pathway suggested that bonediol could induce oxidative stress and activation of detoxification enzymes at 1 uM (3.8-fold). We propose that the compound bonediol may serve as a potential chemopreventive treatment with therapeutic potential against prostate cancer. PMID- 26557705 TI - Effect and Mechanism of Total Flavonoids Extracted from Cotinus coggygria against Glioblastoma Cancer In Vitro and In Vivo. AB - Flavonoids, a major constituent of Cotinus coggygria (CC), have been reported to possess diverse biological activities, including antigenotoxic and hepatoprotective effects; however, few studies have investigated the biological activity of the total flavonoids of Cotinus coggygria, especially in terms of its cytotoxicity in cancer cells. In the present study, the Cotinus coggygria flavonoids (CCF) were extracted from Cotinus coggygria and characterized by HPLC. These results indicated that CCF extracts could inhibit cell proliferation, with IC50 values of 128.49 ug/mL (U87), 107.62 ug/mL (U251), and 93.57 ug/mL (DBTRG 05MG). The current investigation also revealed that CCF induced apoptosis in highly malignant glioblastoma cells, a process that apparently involved the inhibition of Akt coupled with ERK protein expression. This finding suggests that the PI3K/Akt-ERK signaling pathway is regulated by CCF and leads to the inhibition of the glioblastoma cancer cells. Furthermore, a significant antitumor effect of CCF was observed in xenograft animal models of glioblastoma multiforme in vivo. Taken together, these data suggest that CCF is the active component in the Cotinus coggygria plant that offers potential therapeutic modality in the abrogation of cancer cell proliferation, including the induction of apoptosis. PMID- 26557706 TI - Activity of BKM120 and BEZ235 against Lymphoma Cells. AB - Non-Hodgkin lymphomas encompass a heterogeneous group of cancers, with 85-90% arising from B lymphocytes and the remainder deriving from T lymphocytes or NK lymphocytes. These tumors are molecularly and clinically heterogeneous, showing dramatically different responses and outcomes with standard therapies. Deregulated PI3K signaling is linked to oncogenesis and disease progression in hematologic malignancies and in a variety of solid tumors and apparently enhances resistance to antineoplastic therapy, resulting in a poor prognosis. Here, we have evaluated and compared the effects of the pan-PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitor BEZ235 on mantle, follicular, and T-cell lymphomas. Our results suggest that BKM120 and BEZ235 can effectively inhibit lymphoma cell proliferation by causing cell cycle arrest and can lead to cell death by inducing apoptosis and autophagy mediated by ROS accumulation. Despite great advances in lymphoma therapy after the introduction of monoclonal antibodies, many patients still die from disease progression. Therefore, novel treatment approaches are needed. BKM120 and BEZ235 alone and in combination are very effective against lymphoma cells in vitro. If further studies confirm their effectiveness in animal models, they may be promising candidates for development as new drugs. PMID- 26557707 TI - Phylogenetic and Ontogenetic View of Erythroblastic Islands. AB - Erythroblastic islands are a hallmark of mammalian erythropoiesis consisting of a central macrophage surrounded by and interacting closely with the maturing erythroblasts. The macrophages are thought to serve many functions such as supporting erythroblast proliferation, supplying iron for hemoglobin, promoting enucleation, and clearing the nuclear debris; moreover, inhibition of erythroblastic island formation is often detrimental to erythropoiesis. There is still much not understood about the role that macrophages and microenvironment play in erythropoiesis and insights may be gleaned from a comparative analysis with erythropoietic niches in nonmammalian vertebrates which, unlike mammals, have erythrocytes that retain their nucleus. The phylogenetic development of erythroblastic islands in mammals in which the erythrocytes are anucleate underlines the importance of the macrophage in erythroblast enucleation. PMID- 26557708 TI - Symptoms of Posttraumatic Stress after Intensive Care Delirium. AB - INTRODUCTION: Long-term psychological consequences of critical illness are receiving more attention in recent years. The aim of our study was to assess the correlation of ICU-delirium and symptoms of posttraumatic stress disorder (PTSD) anxiety and depression after ICU-discharge in a Danish cohort. METHODS: A prospective observational cohort study assessing the incidence of delirium in the ICU. Psychometrics were screened by validated tools in structured telephone interviews after 2 months (n = 297) and 6 months (n = 248) after ICU-discharge. RESULTS: Delirium was detected in 54% of patients in the ICU and symptoms of PTSD in 8% (2 months) and 6% (6 months) after ICU-discharge. Recall of ICU stay was present in 93%. Associations between ICU-delirium and post-discharge PTSD symptoms were weak and insignificant. Memories of delusions were significantly associated with anxiety after two months. Remaining associations between types of ICU-memories and prevalence of post-discharge symptoms of PTSD, anxiety, and depression were insignificant after adjusting for age. Incidence of ICU-delirium was unaffected by preadmission use of psychotropic drugs. Prevalence of PTSD symptoms was unaffected by use of antipsychotics and sedation in the ICU. CONCLUSION: ICU-delirium did not increase the risk of PTSD-symptoms at 2 and 6 months after ICU discharge. PMID- 26557709 TI - Diagnostic Accuracy of Nonmydriatic Fundus Photography for the Detection of Glaucoma in Diabetic Patients. AB - PURPOSE: To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. METHODS: Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio >= 0.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes >= 0.2. This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. RESULTS: 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. DISCUSSION: NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics. PMID- 26557710 TI - A Fast Semiautomatic Algorithm for Centerline-Based Vocal Tract Segmentation. AB - Vocal tract morphology is an important factor in voice production. Its analysis has potential implications for educational matters as well as medical issues like voice therapy. The knowledge of the complex adjustments in the spatial geometry of the vocal tract during phonation is still limited. For a major part, this is due to difficulties in acquiring geometry data of the vocal tract in the process of voice production. In this study, a centerline-based segmentation method using active contours was introduced to extract the geometry data of the vocal tract obtained with MRI during sustained vowel phonation. The applied semiautomatic algorithm was found to be time- and interaction-efficient and allowed performing various three-dimensional measurements on the resulting model. The method is suitable for an improved detailed analysis of the vocal tract morphology during speech or singing which might give some insights into the underlying mechanical processes. PMID- 26557711 TI - Long-Term Monitoring of Physical Behavior Reveals Different Cardiac Responses to Physical Activity among Subjects with and without Chronic Neck Pain. AB - BACKGROUND: We determined the extent to which heart rate variability (HRV) responses to daily physical activity differ between subjects with and without chronic neck pain. METHOD: Twenty-nine subjects (13 women) with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry), HRV (heart rate monitor), and spatial location (Global Positioning System (GPS)) were recorded for 74 hours. GPS data were combined with a diary to identify periods of work and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated and stratified by period and activity type (lying/sitting, standing, or walking). ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV. RESULTS: The pain group showed a reduced HRV response to physical activity compared with controls (p = .001), according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low- and high-frequency power), even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p = .02). The parasympathetic response to physical activity did not differ between groups. CONCLUSIONS: Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic baroreceptor response to daily physical activity among subjects with chronic neck pain. PMID- 26557712 TI - Trigonella foenum (Fenugreek) Induced Apoptosis in Hepatocellular Carcinoma Cell Line, HepG2, Mediated by Upregulation of p53 and Proliferating Cell Nuclear Antigen. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and most current therapies are of limited efficacy. Trigonella foenum (Fenugreek) is a traditional herbal plant with antitumor activity, although the mechanisms of its activity remain unclear. Herein, a crude methanol extract was prepared from Fenugreek seeds (FCE) and its anticancer mechanism was evaluated, using HepG2 cell line. Growth-inhibitory effect and apoptosis induction of HepG2 cells were evidenced by MTT assay, cell morphology alteration, apoptosis enzyme-linked immunosorbent assay, flow cytometric analysis, caspase-3 activity, and expression of p53, proapoptotic protein, Bax, and proliferating cell nuclear antigen (PCNA) after (100 ~ 500 MUg/mL) FCE treatment for 48 h. Furthermore, FCE was analyzed by Chromatography-Mass Spectrometry (GC/MS). Our results revealed that FCE treatment for 48 h showed a cytotoxic effect and apoptosis induction in a dose-dependent manner that was mediated by upregulation of p53, Bax, PCNA, and caspase-3 activation in HepG2 cells. GC-MS analysis of FCE showed the presence of fourteen bioactive compounds such as Terpenoids and Flavonoids, including two main constituents with anticancer activity, Squalene and Naringenin (27.71% and 24.05%), respectively. Our data introduced FCE as a promising nontoxic herbal with therapeutic potential to induce apoptosis in HepG2 cells through p53, Bax, and PCNA upregulation in caspase-3 dependent manner. PMID- 26557713 TI - Garcinia dulcis Fruit Extract Induced Cytotoxicity and Apoptosis in HepG2 Liver Cancer Cell Line. AB - Garcinia dulcis or locally known in Malaysia as "mundu" belongs to the family of Clusiaceae. The study was conducted to investigate the anticancer potential of different parts of G. dulcis fruit extracts and their possible mechanism of action in HepG2 liver cancer cell line. MTT assay showed that the peel, flesh, and seed extracts of G. dulcis induced cytotoxicity in HepG2 cell line with IC50 values of 46.33 +/- 4.51, 38.33 +/- 3.51, and 7.5 +/- 2.52 ug/mL, respectively. The flesh extract of G. dulcis induced cell cycle arrest at sub-G1 (apoptosis) phase in a time-dependent manner. Staining with Annexin V-FITC and propidium iodide showed that 41.2% of the cell population underwent apoptosis after 72 hours of exposure of the HepG2 cell line to G. dulcis flesh extract. Caspase-3 has been shown to be activated which finally leads to the death of HepG2 cell (apoptosis). GC-MS analysis showed that the highest percentage of compound identified in the extract of G. dulcis flesh was hydroxymethylfurfural and 3 methyl-2,5-furandione, together with xanthones and flavonoids (based on literature), could synergistically contribute to the observed effects. This finding suggested that the flesh extract of G. dulcis has its own potential as cancer chemotherapeutic agent against liver cancer cell. PMID- 26557714 TI - Models of Workplace Incivility: The Relationships to Instigated Incivility and Negative Outcomes. AB - The aim of the study was to investigate workplace incivility as a social process, examining its components and relationships to both instigated incivility and negative outcomes in the form of well-being, job satisfaction, turnover intentions, and sleeping problems. The different components of incivility that were examined were experienced and witnessed incivility from coworkers as well as supervisors. In addition, the organizational factors, social support, control, and job demands, were included in the models. A total of 2871 (2058 women and 813 men) employees who were connected to the Swedish Hotel and Restaurant Workers Union completed an online questionnaire. Overall, the results from structural equation modelling indicate that whereas instigated incivility to a large extent was explained by witnessing coworker incivility, negative outcomes were to a high degree explained by experienced supervisor incivility via mediation through perceived low social support, low control, and high job demands. Unexpectedly, the relationships between incivility (experienced coworker and supervisor incivility, as well as witnessed supervisor incivility) and instigated incivility were moderated by perceived high control and high social support. The results highlight the importance of including different components of workplace incivility and organizational factors in future studies of the area. PMID- 26557715 TI - Impaired Circulating Angiogenic Cells Mobilization and Metalloproteinase-9 Activity after Dynamic Exercise in Early Metabolic Syndrome. AB - Increased levels of adhesion molecules or metalloproteinases (MMPs) may indicate endothelial dysfunction. Exercise mobilizes circulating angiogenic cells (CACs) from bone marrow in healthy subjects, improving vascular function. However, it is unclear whether this mechanism is preserved in the early stages of metabolic syndrome (early MetS). We aimed to evaluate the acute effects of exercise on adhesion molecules, angiogenic factors, MMPs, and CACs in early MetS. Fifteen subjects with early MetS and nine healthy controls underwent an exercise session and a nonexercise session, randomly. Adhesion molecules, angiogenic factors, CACs, and MMPs were evaluated before and after exercise or nonexercise sessions. At baseline, levels of sE-selectin, sICAM-1, and MMP-9 were higher in early MetS than in controls (P <= 0.03). After exercise, sE-selectin, sICAM-1, and MMP-9 levels were still higher in early MetS (P < 0.05). Subjects with early MetS presented less CACs (P = 0.02) and higher MMP-9 activity (P <= 0.04), while healthy controls presented higher MMP-2 activity after exercise. There was no difference between moments in nonexercise session (P > 0.05). In conclusion, subjects with early MetS already presented impaired endothelial function at rest along with a decrease in CACs and an increase in MMP-9 activity in response to exercise. PMID- 26557716 TI - Real-Time Analysis of Temperature Changes in Composite Increments and Pulp Chamber during Photopolymerization. AB - OBJECTIVE: The aim of this study was to evaluate the temperature change at various sites within the composite and on the pulpal side of dentin during polymerization of two composite increments. MATERIALS AND METHODS: Class I cavities prepared in third molars were restored in two composite increments (n = 5). Temperatures were measured for 110 s using eight thermocouples: bottom center of cavity (BC), top center of 1st increment (MC), top center of 2nd increment (TC), bottom corner of cavity (BE), top corner of 1st increment (ME), top corner of 2nd increment (TE), pulpal side of dentin (PD), and center of curing light guide tip (CL). RESULTS: Maximum temperature values ( degrees C) measured during polymerization of 1st increment were MC (59.8); BC (52.8); ME (51.3); CL (50.7); BE (48.4); and PD (39.8). Maximum temperature values during polymerization of 2nd increment were TC 58.5; TE (52.6); MC (51.7); CL (50.0); ME (48.0); BC (46.7); BE (44.5); and PD (38.8). CONCLUSION: Temperature at the floor of the cavity was significantly higher during polymerization of 1st increment compared to 2nd increment. Temperature rise was higher at the center than at the corner and at the top surface than at the bottom surface of each increment. PMID- 26557717 TI - Spoken Word Recognition Errors in Speech Audiometry: A Measure of Hearing Performance? AB - This report provides a detailed analysis of incorrect responses from an open-set spoken word-repetition task which is part of a Dutch speech audiometric test battery. Single-consonant confusions were analyzed from 230 normal hearing participants in terms of the probability of choice of a particular response on the basis of acoustic-phonetic, lexical, and frequency variables. The results indicate that consonant confusions are better predicted by lexical knowledge than by acoustic properties of the stimulus word. A detailed analysis of the transmission of phonetic features indicates that "voicing" is best preserved whereas "manner of articulation" yields most perception errors. As consonant confusion matrices are often used to determine the degree and type of a patient's hearing impairment, to predict a patient's gain in hearing performance with hearing devices and to optimize the device settings in view of maximum output, the observed findings are highly relevant for the audiological practice. Based on our findings, speech audiometric outcomes provide a combined auditory-linguistic profile of the patient. The use of confusion matrices might therefore not be the method best suited to measure hearing performance. Ideally, they should be complemented by other listening task types that are known to have less linguistic bias, such as phonemic discrimination. PMID- 26557718 TI - Towards a Job Demands-Resources Health Model: Empirical Testing with Generalizable Indicators of Job Demands, Job Resources, and Comprehensive Health Outcomes. AB - Studies using the Job Demands-Resources (JD-R) model commonly have a heterogeneous focus concerning the variables they investigate-selective job demands and resources as well as burnout and work engagement. The present study applies the rationale of the JD-R model to expand the relevant outcomes of job demands and job resources by linking the JD-R model to the logic of a generic health development framework predicting more broadly positive and negative health. The resulting JD-R health model was operationalized and tested with a generalizable set of job characteristics and positive and negative health outcomes among a heterogeneous sample of 2,159 employees. Applying a theory driven and a data-driven approach, measures which were generally relevant for all employees were selected. Results from structural equation modeling indicated that the model fitted the data. Multiple group analyses indicated invariance across six organizations, gender, job positions, and three times of measurement. Initial evidence was found for the validity of an expanded JD-R health model. Thereby this study contributes to the current research on job characteristics and health by combining the core idea of the JD-R model with the broader concepts of salutogenic and pathogenic health development processes as well as both positive and negative health outcomes. PMID- 26557719 TI - Inhibition of PI3K Signalling Selectively Affects Medulloblastoma Cancer Stem Cells. AB - Medulloblastoma is the most common malignant brain tumor of childhood. Although survival has slowly increased in the past years, the prognosis of these patients remains unfavourable. In this context, it has been recently shown that the intracellular signaling pathways activated during embryonic cerebellar development are deregulated in MDB. One of the most important is PI3K/AKT/mTOR, implicated in cell proliferation, survival, growth, and protein synthesis. Moreover, a fraction of MDB cells has been shown to posses stemlike features, to express typical neuronal precursor markers (Nestin and CD133), and to be maintained by the hypoxic cerebellar microenvironment. This subpopulation of MDB cells is considered to be responsible for treatment resistance and recurrence. In this study, we evaluated the effects of PI3K/AKT pathway inhibition on primary cultures of MDB and particularly on the cancer stem cell (CSC) population (CD133(+)). PI3K inhibition was able to counteract MDB cell growth and to promote differentiation of stemlike MDB cells. Moreover, PI3K/AKT pathway suppression induced dramatic cell death through activation of the mitochondrial proapoptotic cascade. Finally, analysis on the stem cells fraction revealed that the MDB CSC population is more sensitive to PI3K targeting compared to the whole cancerous population and its nonstem cell counterpart. PMID- 26557720 TI - A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How this Association Was Augmented by Poor Glycaemic Control. AB - Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c >= 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk. PMID- 26557721 TI - HTLV-1 ORF-I Encoded Proteins and the Regulation of Host Immune Response: Viral Induced Dysregulation of Intracellular Signaling. AB - The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with both proliferative and inflammatory disorders. This virus causes a persistent infection, mainly in CD4+ T lymphocyte. The ability to persist in the host is associated with the virus capacity to evade the immune response and to induce infected T-cell proliferation, once the HTLV-1 maintains the infection mainly by clonal expansion of infected cells. There are several evidences that ORF-I encoded proteins, such as p12 and p8, play an important role in this context. The present study will review the molecular mechanisms that HTLV-1 ORF-I encoded proteins have to induce dysregulation of intracellular signaling, in order to escape from immune response and to increase the infected T-cell proliferation rate. The work will also address the impact of ORF-I mutations on the human host and perspectives in this study field. PMID- 26557722 TI - Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling. AB - Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-) alpha signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-alpha and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN alpha-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling. PMID- 26557723 TI - Prophylactic mRNA Vaccination against Allergy Confers Long-Term Memory Responses and Persistent Protection in Mice. AB - Recently, mRNA vaccines have been introduced as a safety-optimized alternative to plasmid DNA-based vaccines for protection against allergy. However, it remained unclear whether the short persistence of this vaccine type would limit memory responses and whether the protective immune response type would be maintained during recurrent exposure to allergen. We tested the duration of protective memory responses in mice vaccinated with mRNA encoding the grass pollen allergen Phl p 5 by challenging them with recombinant allergen, 3.5, 6, and 9 months after vaccination. In a second experiment, vaccinated mice were repeatedly challenged monthly with aerosolized allergen over a period of 7 months. Antibody and cytokine responses as well as lung inflammation and airway hyperresponsiveness were assessed. mRNA vaccination induced robust TH1 memory responses for at least 9 months. Vaccination efficiently suppressed TH2 cytokines, IgE responses, and lung eosinophilia. Protection was maintained after repeated exposure to aerosolized allergen and no TH1 associated pathology was observed. Lung function remained improved compared to nonvaccinated controls. Our data clearly indicate that mRNA vaccination against Phl p 5 induces robust, long-lived memory responses, which can be recalled by allergen exposure without side effects. mRNA vaccines fulfill the requirements for safe prophylactic vaccination without the need for booster immunizations. PMID- 26557725 TI - Foley Catheter versus Vaginal Misoprostol for Labour Induction. AB - Objectives. To compare the efficacy and safety of intravaginal misoprostol with transcervical Foley catheter for labour induction. Material and Methods. One hundred and four women with term gestation, with Bishop score < 4, and with various indications for labour induction were randomly divided into two groups. In Group I, 25 MUg of misoprostol tablet was placed intravaginally, 4 hourly up to maximum 6 doses. In Group II, Foley catheter 16F was placed through the internal os of the cervix under aseptic condition and then inflated with 50 cc of sterile saline. Statistical analysis was done using SPSS software. Results. The induction to delivery interval was 14.03 +/- 7.61 hours versus 18.40 +/- 8.02 hours (p < 0.01). The rate of vaginal delivery was 76.7% versus 56.8% in misoprostol and transcervical Foley catheter group, respectively. Uterine hyperstimulation was more common with misoprostol. Neonatal outcome was similar in both the groups. Conclusion. Intravaginal misoprostol is associated with a shorter induction to delivery interval as compared to Foley's catheter and it increases the rate of vaginal delivery in cases of unripe cervix at term. Transcervical Foley catheter is associated with a lower incidence of uterine hyperstimulation during labour. PMID- 26557724 TI - Integrating Patient-Reported Outcome Measures into Routine Cancer Care: Cancer Patients' and Clinicians' Perceptions of Acceptability and Value. AB - INTRODUCTION: Despite growing interest in integrating patient-reported outcome (PRO) measures of symptoms and functional status into routine cancer care, little attention has been paid to patients' and clinicians' perceptions of acceptability and value. METHODS: A two-phase qualitative study was conducted to develop a web based PRO screening system with 21 items assessing symptoms (e.g., nausea) and functional status. Phase 1 involved cognitive interviews with 35 cancer outpatients (n=9 breast chemotherapy, radiation for prostate (n=8) or head and neck cancer (n=10), and n=8 bone marrow transplant [BMT]). In Phase 2, we evaluated the acceptability and perceived value of reviewing a PRO measure during real-time clinical encounters with 39 additional outpatients (n=10 breast, n=9 head and neck, n=10 prostate, n=10 BMT) and 12 clinicians (n=3 breast, n=2 head and neck, n=4 prostate, n=3 BMT). At least 20% of patients were >=60 years, African American, or <= high school. RESULTS: Patients felt that their PRO summary of symptoms and functional status was helpful in discussing health issues with clinicians (92%), wanted to review their results with clinicians during future visits (82%), and would recommend it to other patients (87%). Clinicians found the PRO summary to be easy to interpret (83%), most helpful for documenting the Review of Symptoms (92%), and would recommend it to future patients (92%). Over 90% of clinicians reported that consultation time did not increase. CONCLUSION: Both cancer patients and clinicians reported that discussing a PRO summary of symptoms and functional status during an outpatient visit was useful, acceptable, and feasible. PMID- 26557726 TI - Incidence, Risk Factors, Prognosis, and Electrophysiological Mechanisms of Atrial Arrhythmias after Lung Transplantation. AB - OBJECTIVE: To investigate incidence and timing, risk factors, prognostic significance, and electrophysiological mechanisms of atrial arrhythmia (AA) after lung transplantation. BACKGROUND: Although new-onset AA is common after thoracic surgery and is associated with poorer outcomes, prognostic and mechanistic data is sparse in lung transplant populations. METHOD: A total of 293 consecutive isolated lung transplant recipients without known AA were retrospectively reviewed. Mean follow-up was 28+/-17 months. Electrophysiology studies (EPS) were performed in 25 patients with AA. RESULTS: The highest incidence of new-onset AA after lung transplantation occurred within 30 days postoperative AA, (25 % of all patients). In multivariable analysis, postoperative AA was associated with double lung transplantation (OR 2.79; p=0.005) and lower mean pulmonary artery pressure (OR 0.95; p=0.027). Patients with postoperative AA had longer hospital stays (21 days vs 12 days; p<0.001). Postoperative AA was independently associated with late AA (HR 13.52; p<0.001) but not mortality (HR 1.55; p=0.14). In EPS, there were 14 patients with atrial flutter alone and 11 with atrial flutter and fibrillation. Of all EPS patients, 20 (80%) had multiple AA mechanisms, including peritricuspid flutter (48%), perimitral flutter (36%), right atrial incisional reentry (24%), focal tachycardia from recipient pulmonary vein (PV) antrum (32 %), focal PV fibrillation (24%), and left atrial roof flutter (20%). Left atrial mechanisms were present in 80% (20/25) of EPS patients and originated from the anastomotic PV antrum. CONCLUSIONS: Postoperative AA was independently associated with longer length of stay and late AA but not mortality. Pleomorphic PV antral arrhythmogenesis from native PV antrum is the main cause of AA after lung transplantation. PMID- 26557727 TI - THE EFFECT OF GLUCOCORTICOIDS ON BONE AND MUSCLE. AB - This article examines the current knowledge of the effects of both exogenous and endogenous glucocorticoids on bone and muscle. It demonstrates the similarity of effects of supraphysiologic loads of glucocorticoids regardless of whether they enter the body in the form of medication or are manufactured by the body in response to stimuli such as inflammation. The effects of endogenous glucocorticoids and the systemic inflammatory response resulting from pediatric burn injury are compared and the difficulty in sorting out which of the two factors is responsible for the ultimate effects on bone and muscle is pointed out. The focus then switches to the body's response to the influence of both glucocorticoids and inflammatory cytokines and evidence supporting a common pathway of response to oxidative damage caused by both is discussed. Current recommended medical management of glucocorticoid-induced bone and muscle loss is discussed and the failure to reconcile current management with known mechanisms is highlighted. PMID- 26557728 TI - Is It Possible to Differentiate Chronic Kidney Disease and Preeclampsia by means of New and Old Biomarkers? A Prospective Study. AB - OBJECTIVE: Chronic kidney disease (CKD) and preeclampsia (PE) may both present with hypertension and proteinuria in pregnancy. Our objective is to test the possibility of distinguishing CKD from PE by means of uteroplacental flows and maternal circulating sFlt-1/PlGF ratio. DESIGN: Prospective analysis. POPULATION: Seventy-six patients (35 CKD, 24 PE, and 17 other hypertensive disorders), with at least one sFlt-1/PlGF and Doppler evaluation after the 20th gestational week. METHODS: Maternal sFlt-1-PlGF were determined by immunoassays. Abnormal uterine artery Doppler was defined as resistance index >= 0.58. Umbilical Doppler was defined with gestational-age-adjusted Pulsatility Index. Clinical diagnosis was considered as reference. Performance of Doppler study was assessed by sensitivity analysis; sFlt-1/PlGF cut-off values were determined by ROC curves. RESULTS: The lowest sFlt-1/PlGF ratio (8.29) was detected in CKD, the highest in PE (317.32) (P < 0.001). Uteroplacental flows were mostly preserved in CKD patients in contrast to PE (P < 0.001). ROC analysis suggested two cut-points: sFlt-1/PlGF >= 32.81 (sensitivity 82.93%; specificity 91.43%) and sFlt-1/PlGF >= 78.75 (sensitivity 62.89%, specificity 97.14%). Specificity reached 100% at sFlt-1/PlGF >= 142.21 (sensitivity: 48.8%). Early-preterm delivery was associated with higher sFlt-1/PlGF ratio and abnormal uteroplacental flows relative to late-preterm and term deliveries. CONCLUSIONS: sFlt-1/PlGF ratio and uteroplacental flows significantly correlated with PE or CKD and preterm delivery. PMID- 26557730 TI - LLLT for Female Infertility: No Longer Just a Dream. PMID- 26557729 TI - Effects of Long-Term Statin Therapy in Coronary Artery Disease Patients with or without Chronic Kidney Disease. AB - INTRODUCTION: The effect of long-term statin therapy is essential for secondary prevention of adverse clinical outcomes of coronary artery disease (CAD) patients. No study has compared the effects of long-term statin treatment in CAD patients with or without chronic kidney disease (CKD) and CKD only patients. METHODS: We compared the effects of long-term statin therapy (average follow-up time 5.79 years) in terms of major adverse cardiovascular events (MACE), all cause death, and cardiac death among 570 CAD patients with or without CKD and 147 CKD only patients. RESULTS: The all-cause death and cardiac death of the patients with CAD and CKD (24.4% and 20.4%) doubled those of CAD only patients (10.7% and 9.1%) (P < 0.001). Long-term statin therapy dramatically reduced the rates of both MACE and all-cause death/cardiac death (by 20.5% and 28.6%/27.7%, resp.) in CAD and CKD patients. CKD only patients had no significant adverse clinical outcomes and were not responsive to long-term statin therapy. CONCLUSION: Chinese CAD patients with CKD had dramatically high rates of adverse clinical outcomes; for them, long-term statin therapies were exceptionally effective in improving morbidity and mortality. CKD patients who had no cardiovascular disease initially can prognose good clinical outcomes and do not require statin treatment. PMID- 26557731 TI - Effects of the bleaching procedures on enamel micro-hardness: Plasma Arc and diode laser comparison. AB - BACKGROUND AND AIMS: One of the major side effects of vital bleaching is the reduction of enamel micro-hardness. The purpose of this study was to evaluate the influence of two different bleaching systems, Plasma Arc and GaAlAs laser, on the enamel micro-hardness. MATERIALS AND METHODS: 15 freshly extracted human third molars were sectioned to prepare 30 enamel blocks (5*5 mm). These samples were then randomly divided into 2 groups of 15 each (n=15): a plasma arc bleaching group (: 350-700 nm) + 35% Hydrogen Peroxide whitening gel and a laser bleaching group (GaAlAs laser, lambda: 810 nm, P: 10 W, CW, Special Tip) + 35% Hydrogen Peroxide whitening gel. Samples were subjected to the Vickers micro-hardness test (VHN) at a load of 50 g for 15s before and after treatment. Data were statistically analyzed by a Mann-Whitney test (p<=0.05). RESULTS: In the GaAlAs laser group, the enamel micro-hardness was 618.2 before and was reduced to 544.6 after bleaching procedures. In the plasma arc group, the enamel micro-hardness was 644.8 before and 498.9 after bleaching. Although both techniques significantly reduced VHN, plasma arc bleaching resulted in a 22.62% reduction in VHN for enamel micro-hardness, whereas an 11.89% reduction in VHN was observed for laser bleaching; this difference is statistically significant (p<0.001). CONCLUSION: Both bleaching techniques reduced enamel micro-hardness, although the reduction is much less significant with the GaAlAs laser than with the plasma arc. Therefore GaAlAs laser bleaching has fewer harmful effects than plasma arc in respect to enamel micro-hardness reduction. PMID- 26557732 TI - Effect of Stress-Free Therapy on immune system: Induction of Interleukin 10 expression in lymphocytes through activation of CD19(+) CD24(hi) CD38(hi) regulatory B Cells. AB - BACKGROUND AND AIMS: Mild thermal treatment with "Pinpoint Plantar Long wavelength Infrared Light Irradiation (PP-LILI)" named as Stress-Free Therapy((r)) increases peripheral-deep body temperature and blood flow, and improves multiple disorders including hyperpiesia, type II diabetes and cardiovascular patients. Immunomodulatory effects of PP-LILI were investigated. MATERIALS AND METHODS: Seven healthy individuals and 4 people with underlying medical condition (UMC) participated in this study. Participants were given PP LILI stimuli twice a week over 3 weeks and followed with placebo stimuli over 3 weeks. This set of sessions was repeated 3 times. For analyses, fresh peripheral mononuclear cells from participants were stained with fluorescencedye conjugated monoclonal antibodies and changes in populational compositions and IL-10 expression levels were observed by flow cytometry. RESULTS: Distinct expression of IL-10 in lymphocytes was induced by PP-LILI from the second session in the healthy individuals. This induction was terminated during the following placebo sessions. PP-LILI induced activation of CD19(+) CD24(hi) CD38(hi) regulatory B cells in every session prior to induce the IL-10 in major lymphocytes. Activated regulatory B cells in the individuals with UMC decreased as same levels of healthy individuals after second PP-LILI session and re-activated with the stimuli. Significant population changes in neither regulatory T cells nor proinflammatory IL-17A expressing CD4(+) T cells were observed. CONCLUSIONS: PP LILI is a potent immunomodulatory inducer that activates regulatory B cells and consequent IL-10 expression in lymphocytes. Moreover, its stimulatory intervals down-regulate the higher activation of regulatory B cells and lymphocyte's IL-10 expression occurred by UMC to the healthy people's level. PMID- 26557733 TI - Er:YAG laser dentistry in special needs patients. AB - OBJECTIVE: Between a quarter and a third of adults with intellectual disability is estimated to have dental anxiety. Unpleasant stimuli, such as the injection of local anaesthesia or the noise and vibration of rotary instruments, may provoke anxiety and subsequent low compliance until the opposition to the treatment. The use of Er:YAG laser in conservative dentistry had a great development in these last years thank to new devices and also to their advantages when compared to the conventional instruments. The aim of this clinical study was to show the advantages of the Er:YAG laser in the conservative treatment of Special Care patients. METHODS: Four cases are here described to show the Er:YAG laser use in our Unit on special needs patients. RESULTS AND CONCLUSIONS: Based on the experience gained on conservative laser-assisted treatments performed in a time of 5 years at our Dentistry, Special Needs and Maxillo-Facial Surgery Unit we may affirm that Er:YAG laser may be considered as a good way to improve the cooperation, to reduce anxiety related to rotating instruments and to reach better results with equal or shorter operating times. PMID- 26557734 TI - Efficacy of low level laser therapy on painful diabetic peripheral neuropathy. AB - BACKGROUND & AIMS: Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) Materials & methods: The study design is pre-post observational design. After obtaining ethical clearance and informed consent, 19 T2DM subjects were screened and confirmed for peripheral neuropathy in an outpatient setting with biochemical parameter, pain scale and Michigan Neuropathy Screening Instrument (MNSI). Low Level Laser therapy was irradiated through scanning mode with dosage of 3.1J/cm(2) on the plantar and dorsum of the foot and 3.4j/cm(2) with contact method for 10days and all subjects were reassessed at the end of the 10 day. Descriptive statistics and paired' test was used to analyze the pre-post finding within the group. Level of significance was set at p<0.05 RESULTS: The result analysis showed significant reduction in Pain using VAS scale (6.47 +/- 0.84 to 1.21 +/- 0.78 (p<0.001), MNSI (5.52 +/- 1.26 to 2.71 +/- 0.97 (reduction in Vibration perception threshold (32.68 +/- 6.08 to 24.84 +/- 4.29 (<0.001) and a significant increase in the temperature from baseline to post intervention (30.01 +/- 2.11 to 31.75 +/- 1.03 (p<0. 001). CONCLUSION: In the present study, Low level laser therapy was found to be effective in type 2 DM with peripheral neuropathy. PMID- 26557735 TI - Modulation of inflammatory response of wounds by antimicrobial photodynamic therapy. AB - BACKGROUND AND AIMS: Management of infections caused by Pseudomonas aeruginosa is becoming difficult due to the rapid emergence of multi-antibiotic resistant strains. Antimicrobial photodynamic therapy (APDT) has a lot of potential as an alternative approach for inactivation of antibiotic resistant bacteria. In this study we report results of our investigations on the effect of poly-L-lysine conjugate of chlorine p6 (pl-cp6) mediated APDT on the healing of P.aeruginosa infected wounds and the role of Nuclear Factor kappa B (NF-kB) induced inflammatory response in this process. MATERIALS AND METHOD: Excisional wounds created in Swiss albino mice were infected with ~10(7) colony forming units of P.aeruginosa. Mice with wounds were divided into three groups: 1) Uninfected, 2) Infected, untreated control (no light, no pl-cp6), 3) Infected, APDT. After 24 h of infection (day 1 post wounding), the wounds were subjected to APDT [pl-cp6 applied topically and exposed to red light (660 +/- 25 nm) fluence of ~ 60 J/cm(2)]. Subsequent to APDT, on day 2 and 5 post wounding (p.w), measurements were made on biochemical parameters of inflammation [toll like receptor-4 (TLR 4), NF-kB, Inteleukin (IL)-[1alpha, IL-beta, and IL-2)] and cell proliferation [(fibroblast growth factor-2 (FGF-2), alkaline phosphatase (ALP)]. RESULTS: In comparison with untreated control, while expression of TLR-4, NF-kB (p105 and p50), and proinflammatory interleukins (IL-1alpha, IL-1beta,IL-2) were reduced in the infected wounds subjected to APDT, the levels of FGF-2 and ALP increased, on day 5 p.w. CONCLUSION: The measurements made on the inflammatory markers and cell proliferation markers suggest that APDT reduces inflammation caused by P.aeruginosa and promotes cell proliferation in wounds. PMID- 26557736 TI - Low level nitrogen laser therapy in pulmonary tuberculosis. AB - BACKGROUND AND AIMS: WHO estimated 9 million new Tuberculosis cases and 1.5 million TB deaths in 2013. Globally 480000 Multi drug resistant tuberculosis cases were noted and majority of them were in India, China and Russian federation. Multi drug resistant tuberculosis cases are difficult to treat and have high mortality. Presently, it was aimed to assess prevalence of drug resistance in M. tuberculosis isolates in Central India, to check the in-vitro effect of N2 Laser on M. tuberculosis and to study the therapeutic effect of intra cavitary N2 laser on pulmonary Tuberculosis cases not responding to chemotherapy. MATERIALS AND METHODS: Drug sensitivity testing was carried out on 567 isolates of M. tuberculosis by proportion method. To check the effect of N2 laser on M. tuberculosis, suspension spread on LJ plate and part of the plate exposed to N2 laser for 10 min and plate incubated for 4 weeks to see the effect. For exposure to lung cavity a needle was introduced into the lung through which fiber was passed to the cavity for N2 laser irradiation for 10 min. RESULTS: Only 12.8% isolates of M. tuberculosis were sensitive to all anti-Tubercular drugs and 21.5% were found to be resistant to Rifampicin qualifying definition of Multi drug resistant tuberculosis. Bactericidal effect for N2 laser was seen in-vitro on exposure to N2 laser. Clinical improvement occurred in 90% of the 96 patients; 60% of the patients showed improvement on their X-rays and 75% turned out to be Acid fast bacilli smear negative in 4 to 15 days. CONCLUSIONS: Intra-cavitory N2 laser therapy was found to have remarkable success as an adjunct to chemotherapy. PMID- 26557737 TI - Low Level Laser Therapy: A Panacea for oral maladies. AB - AIM: To review the applications of low level laser therapy on various soft and hard oral tissues. A variety of therapeutic effects of Low Level Laser Therapy have been reported on a broad range of disorders. It has been found amenably practical in dental applications including soft as well as hard tissues of the oral cavity. LLLT has been found to be efficient in acceleration of wound healing, enhanced remodelling and bone repair, regeneration of neural cells following injury, pain attenuation, endorphin release stimulation and modulation of immune system. The aforementioned biological processes induced by Low level lasers have been effectively applied in treating various pathological conditions in the oral cavity. With is article, we attempt to review the possible application of Low Laser Therapy in the field of dentistry. PMID- 26557738 TI - Traumatic Brain Injury Rehabilitation in Hong Kong: A Review of Practice and Research. AB - BACKGROUND: The rising public health concern regarding traumatic brain injury (TBI) implies a growing need for rehabilitation services for patients surviving TBI. METHODS: To this end, this paper reviews the practices and research on TBI rehabilitation in Hong Kong so as to inform future developments in this area. This paper begins by introducing the general situation of TBI patients in Hong Kong and the need for rehabilitation. Next, the trauma system in Hong Kong is introduced. Following that is a detailed description of the rehabilitation services for TBI patients in Hong Kong, as exemplified by a rehabilitation hospital in Hong Kong. This paper will also review intervention studies on rehabilitating brain-injured populations in Hong Kong with respect to various rehabilitation goals. Lastly, the implications of culture-related issues will be discussed in relation to TBI. RESULTS/CONCLUSIONS: The intervention studies conducted in Hong Kong are generally successful in achieving various rehabilitative outcomes. Additionally, certain cultural-related issues, such as the stigma associated with TBI, may impede the rehabilitative process and lead to various psychosocial problems. PMID- 26557739 TI - Carbon Monoxide Inhibits Tenascin-C Mediated Inflammation via IL-10 Expression in a Septic Mouse Model. AB - Tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is specifically induced upon tissue injury and infection and during septic conditions. Carbon monoxide (CO) gas is known to exert various anti-inflammatory effects in various inflammatory diseases. However, the mechanisms underlying the effect of CO on TN C-mediated inflammation are unknown. In the present study, we found that treatment with LPS significantly enhanced TN-C expression in macrophages. CO gas, or treatment with the CO-donor compound, CORM-2, dramatically reduced LPS-induced expression of TN-C and proinflammatory cytokines while significantly increased the expression of IL-10. Treatment with TN-C siRNA significantly suppressed the effects of LPS on proinflammatory cytokines production. TN-C siRNA did not affect the CORM-2-dependent increase of IL-10 expression. In cells transfected with IL 10 siRNA, CORM-2 had no effect on the LPS-induced expression of TN-C and its downstream cytokines. These data suggest that IL-10 mediates the inhibitory effect of CO on TN-C and the downstream production of proinflammatory cytokines. Additionally, administration of CORM-2 dramatically reduced LPS-induced TN-C and proinflammatory cytokines production while expression of IL-10 was significantly increased. In conclusion, CO regulated IL-10 expression and thus inhibited TN-C mediated inflammation in vitro and in vivo. PMID- 26557740 TI - Prevalence of obstructive sleep apnea among patients with coronary artery disease in Saudi Arabia. AB - BACKGROUND: Despite the association between obstructive sleep apnea (OSA) and coronary artery disease (CAD), few studies have investigated this issue in Saudi Arabia. OBJECTIVES: This study aimed to identify the prevalence of OSA among CAD patients. SUBJECTS AND METHODS: This was a cross-sectional (descriptive) study conducted at King Abdul-Aziz University Hospital in Jeddah, Saudi Arabia from April 2012 to December 2013. All consecutive patients referred to the cardiac catheterization lab for coronary angiography who exhibited evidence of CAD were included in this study. This study was conducted in two stages. During the first stage, each participant was interviewed individually. The administered interview collected data pertaining to demographics, comorbidities, and the STOP-BANG questionnaire score. The second stage of this study consisted of a diagnostic overnight polysomnography (PSG) of 50% of the subjects at high risk for OSA according to the STOP-BANG questionnaire. RESULTS: Among the patients with CAD (N = 156), 128 (82%) were categorized as high risk for developing OSA. PSG was conducted on 48 patients. The estimated prevalence of OSA in the study sample was 56.4%. Approximately 61% of the documented sleep apnea patients suffered from moderate to severe OSA. CONCLUSION: This local study concurs with reports in the literature indicating that OSA is very common among CAD patients. PMID- 26557741 TI - Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population. AB - BACKGROUND: The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. METHODS: Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. RESULTS: In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. CONCLUSION: In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made. PMID- 26557742 TI - Radius of proximal isovelocity surface area in the assessment of rheumatic mitral stenosis: Connecting flow to anatomy and hemodynamics. AB - BACKGROUND: Echocardiographic assessment of left atrial pressure (LAP) in mitral stenosis (MS) is controversial. We sought to examine the role of the radius of the proximal isovelocity surface area (PISA-r) in the assessment of the hemodynamic status of MS after fixing the aliasing velocity (Val). METHODS AND RESULTS: We studied 42 candidates of balloon mitral valvuloplasty (BMV), for whom pre-BMV echocardiography was done and LAP invasively measured before dilatation. PISA-r was calculated after fixing aliasing velocity to 33 cm/s. In addition, the ratio IVRT/Te'-E was also measured, where IVRT was isovolumic relaxation time, and Te'-E was the time difference between the onset of mitral flow E-wave and mitral annular early diastolic velocity. IVRT/Te'-E and PISA-r showed a strong correlation with LAP (r = -0.715 and -0.637, all p < 0.001) and with right-sided pressures. In addition, PISA-r correlated with mitral valve area by planimetry method (MVA) and with left ventricular outflow tract stroke volume (r = 0.66 and 0.71, all p < 0.001). Receiver operator characteristic curve (ROC-curve) showed that PISA-r was not inferior to IVRT/Te'-E in differentiating LAP ?25 from <25 mmHg. CONCLUSION: Provided that Val is set to a constant of 33 cm/s, PISA-r can assess the hemodynamic status of MS, and seems a simple alternative to the tedious IVRT/Te'-E for estimation of LAP. PMID- 26557743 TI - Objective and subjective image quality with prospectively gated versus ECG controlled tube current modulation using 256-slice computed tomographic angiography. AB - INTRODUCTION: Radiation exposure is one of the major limitations of computed tomographic coronary angiography (CTA). The purpose of this study was to compare the objective and subjective image quality and radiation dose using prospective ECG gating (PGA) versus ECG-controlled tube current modulation (ECTCM) scanning techniques. METHODS: A prospective, single-center study was performed at Prince Sultan Cardiac Centre, Qassim, Saudi Arabia. A total of 104 patients with low-to- intermediate probability of coronary artery disease (CAD) underwent CTA with either PGA or ECTCM acquisition. PGA was performed during the study period and compared with the last 50 CTAs previously done using ECTCM. A 4-point scale was used to assess the image quality subjectively. Objective image quality was assessed using image signal, noise, and signal-to-noise ratio (SNR). RESULTS: Patient's Baseline characteristics were not different between the two scanning protocols. The 4-point score of subjective image quality showed no significant differences between the PGA and ECTCM scans (2.9 +/- 0.7, 2.96 +/- 0.7, respectively; p = 0.87). The objective image quality showed significantly higher noise and lower SNR with PGA compared with ECTCM (31 +/- 9, 27 +/- 9, respectively; p < 0.001 for noise) and (15 +/- 5, 17 +/- 7, respectively; p < 0.001 for SNR), with no statistical difference in the image signal (434 +/- 123, 425 +/- 103 HU, respectively, p = 0.7). Radiation exposure was significantly lower with PGA than with ECTCM. The dose-length product (DLP) for PGA was 334 +/- 130 mGy, compared with 822 +/- 286 mGy for the ECTCM. This corresponds to a 59% reduction in radiation exposure (p < 0.0001). CONCLUSIONS: Although prospective ECG-triggered axial scanning increased image noise, it maintained subjective image quality and was associated with a 59% reduction in radiation exposure when compared with ECTCM. PMID- 26557744 TI - Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration? AB - There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l) is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l) is considered deficiency. Levels below 50 nmol/l (20 ng/l) are linked independently to cardiovascular morbidity and mortality. PMID- 26557745 TI - Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes. AB - Significant left main coronary artery (LMCA) stenosis is not rare and reported 3 to 10% of patients undergoing coronary angiography. Unprotected LMCA intervention is a still clinical challenge and surgery is still going to be a traditional management method in many cardiac centers. With a presentation of drug eluting stent (DES), extensive use of IVUS and skilled operators, number of such interventions increased rapidly which lead to change in recommendation in the guidelines regarding LMCA procedures in the stable angina (Class 2a recommendation for ostial and shaft lesion and class 2b recommendation for distal bifurcation lesion). However, there was not clear consensus about the management of unprotected LMCA lesion associated with acute myocardial infarction (MI) with a LMCA culprit lesion itself or distinct culprit lesion of other major coronary arteries. Surgery could be preferred as an obligatory management strategy even in the high risk patients. With this review, we aimed to demonstrate treatment strategies of LMCA disease associated with acute coronary syndrome, particularly acute myocardial infarction (MI). In addition, we presented a short case series with LMCA lesion and ST elevated acute MI in which culprit lesion placed either in the left anterior descending artery or circumflex artery. We reviewed the current medical literature and propose simple algorithm for management. PMID- 26557746 TI - Congenital ventricular diverticulum and MI - Diagnostic challenges and implications. AB - The use of modern cardiac imaging techniques suggests that congenital ventricular diverticulum (CVD) may be more common than generally believed and may present asymptomatically in adult life. We present a case of congenital left ventricular diverticulum diagnosed in a patient presenting with myocardial infarction (MI). The case highlights the importance of the differential diagnosis of CVD from post infarct left ventricular aneurysms (PILVA) and suggests that adult studies using modern imaging techniques are needed to define the prognosis for asymptomatic CVD in order to guide management. PMID- 26557747 TI - Functional assessment of sequential coronary artery fistula and coronary artery stenosis with fractional flow reserve and stress adenosine myocardial perfusion imaging. AB - Coronary artery fistula is an abnormal connection between one coronary artery to another coronary artery or cardiac chambers. The coronary artery fistula may cause significant shunting of blood and cause "pseudo-stenosis" or "steal phenomenon". This will also accentuate pre-existing mild-moderate de novo coronary lesions with resultant greater pressure gradient difference across the lesions. Thus, fractional flow reserve can be a useful tool to guide intervention decision on the coronary artery fistula. There are very few published reports regarding the use of FFR to assess coronary artery fistula. In fact, there is no outcome data regarding the deferment of coronary artery fistula intervention when the FFR is not physiologically significant. This case highlighted the use of FFR to evaluate the functional significance of coronary fistula in the setting of ischemia evaluation and it was proven to be safe to defer intervention with good 3 year clinical outcome. Stress adenosine myocardial perfusion imaging correlated with the FFR result. PMID- 26557748 TI - A huge cardiac hydatid cyst: An unusual cause of chest pain revealing multivisceral hydatidosis in a young woman. AB - Hydatid disease remains endemic in some parts of the world. Cardiac hydatidosis with multivisceral involvement is uncommon but potentially fatal. We report the case of a 36-year-old Tunisian woman admitted with chest pain and T-wave inversion in the inferior leads on her electrocardiogram. Transthoracic echocardiography revealed a large hydatid cyst in the epicardium throughout the left ventricle. Thoraco-abdominal computerized tomography (CT) scan showed several hydatid cysts in the left lung, the liver, and in both breasts. After one week of albendazole treatment, surgical excision of the cardiac cyst on cardiopulmonary bypass was carried out as well as excision of the pulmonary and breast cysts. The postoperative course was uneventful and albendazole treatment was continued for six months. Though hydatid cardiac involvement is very rare, it should be considered in the differential diagnosis of atypical chest pain in young patients, especially those living in regions where hydatid disease is endemic. PMID- 26557749 TI - Spontaneous myopericarditis in a patient under dexamethasone: A double-edged sword? AB - A majority of acute pericarditis cases have some degree of myocarditis. Viruses are the common etiological factor of this disease. Corticosteroids are considered for treatment, especially in recurrent models of the disease. In this article, we report the case of a 47-year-old man with myopericarditis who was under daily intra-muscular dexamethasone injection for an unknown reason. This is a unique case of spontaneous myopericarditis under corticosteroid abuse that has not been reported previously. PMID- 26557750 TI - Consider the genetic and myopathic background, familial occurrence, and alternative definitions of left ventricular hypertrabeculation/noncompaction. PMID- 26557751 TI - Reply to: Consider the genetic and myopathic background, familial occurrence, and alternative definitions of left ventricular hypertrabeculation/noncompaction. PMID- 26557752 TI - Identify practice gaps in medication education through surveys to patients and physicians. AB - BACKGROUND: Effective communication and education formats between health care providers and patients about medication use are associated with patients' satisfaction, recall of information, and eventually their health status. Limited research exists on physician-delivered education interventions, as well as on whether the current content of medication education and delivery formats satisfies the needs of both patients and physicians. Our objective was to identify the practice gaps regarding medication education content and delivery. METHODS: Separate surveys were obtained from ambulatory care patients presenting to the outpatient pharmacy for medication pickups, and physicians working at the hospital clinics. RESULTS: A total of 108 patients completed the patient survey, and 116 hospital clinic physicians completed the physician survey. Female patients had a higher degree of concern regarding medication information compared with male patients (4.04+/-0.65 versus 3.58+/-0.66, P=0.001). Physicians were less likely to educate patients regarding their medications' on drug-drug interactions (24.3%), drug-food interactions (24.3%), and what to do about their prescriptions if an adverse reaction is experienced (24.3%) during physician patient encounters. Patients' most desired education format was physician counseling (82.4%) and the second most desired education format was pharmacist counseling (50.9%). Medication device demonstration (7.0%) was the least used educational format delivered to patients by physicians, and patients would like to see an increased education delivery format through medication device demonstration (Method desired [MD] - Method received [MR] =12.0%). Patients would like to see expanded roles of patient focused handout (MD-MR=22.2%), telephone consultation (21.2%), pharmacist counseling (12.9%), the use of medication database embedded within the hospital information system (12.2%) and device demonstration (12.0%). CONCLUSION: This study illustrates that there are practice gaps in current medication education both in terms of content and delivery format. The study provided valuable information in designing and implementing future education activities that are drivers of good medication use and adherence. PMID- 26557753 TI - Heart rate variability biofeedback in patients with alcohol dependence: a randomized controlled study. AB - BACKGROUND AND OBJECTIVE: In patients with alcohol dependence, ethyl-toxic damage of vasomotor and cardiac autonomic nerve fibers leads to autonomic imbalance with neurovascular and cardiac dysfunction, the latter resulting in reduced heart rate variability (HRV). Autonomic imbalance is linked to increased craving and cardiovascular mortality. In this study, we sought to assess the effects of HRV biofeedback training on HRV, vasomotor function, craving, and anxiety. METHODS: We conducted a randomized controlled study in 48 patients (14 females, ages 25-59 years) undergoing inpatient rehabilitation treatment. In the treatment group, patients (n=24) attended six sessions of HRV biofeedback over 2 weeks in addition to standard rehabilitative care, whereas, in the control group, subjects received standard care only. Psychometric testing for craving (Obsessive Compulsive Drinking Scale), anxiety (Symptom Checklist-90-Revised), HRV assessment using coefficient of variation of R-R intervals (CVNN) analysis, and vasomotor function assessment using laser Doppler flowmetry were performed at baseline, immediately after completion of treatment or control period, and 3 and 6 weeks afterward (follow-ups 1 and 2). RESULTS: Psychometric testing showed decreased craving in the biofeedback group immediately postintervention (OCDS scores: 8.6+/-7.9 post biofeedback versus 13.7+/-11.0 baseline [mean +/- standard deviation], P<0.05), whereas craving was unchanged at this time point in the control group. Anxiety was reduced at follow-ups 1 and 2 post-biofeedback, but was unchanged in the control group (P<0.05). Following biofeedback, CVNN tended to be increased (10.3%+/-2.8% post-biofeedback, 10.1%+/-3.5% follow-up 1, 10.1%+/-2.9% follow-up 2 versus 9.7%+/-3.6% baseline; P=not significant). There was no such trend in the control group. Vasomotor function assessed using the mean duration to 50% vasoconstriction of cutaneous vessels after deep inspiration was improved following biofeedback immediately postintervention and was unchanged in the control group (P<0.05). CONCLUSION: Our data indicate that HRV biofeedback might be useful to decrease anxiety, increase HRV, and improve vasomotor function in patients with alcohol dependence when complementing standard rehabilitative inpatient care. PMID- 26557754 TI - Linezolid for the treatment of hospital-acquired pneumonia in a Chinese tertiary hospital. PMID- 26557755 TI - Statins and cancers. AB - Statins (inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) are a group of drugs used to treat lipid disorders. They inhibit cholesterol synthesis at an early stage of the biosynthesis pathway, thus eliminating numerous metabolites involved in the cycle. Numerous studies point to different possible effects of statins on cancer cells. Statins inhibit growth of a tumor, invasion and metastasis formation. They block the production of isoprenoids, which are necessary for post-translational modifications of many proteins, including those involved in normal cell signaling. They also contribute to the reduction in the expression of vascular endothelial growth factor, sensitize tumor cells to NK cell activity, and modify the body inflammatory response. Due to different pharmacokinetic properties of individual statins, they may have opposite effects on the risk of cancer. Currently, most information on the effects of statins on the risk of developing cancer is obtained from observational studies. The studies have different results depending on the location of cancer. The protective effect of statins was observed in the meta-analysis of numerous studies including prostate cancer, stomach cancer, esophagus cancer, and hepatocellular carcinoma; however, it has not yet been confirmed that statins influence the risk of developing colorectal cancer, breast cancer, or lung cancer. The protective effect of statins on the development of many kinds of cancer can be a valuable and easy way to reduce morbidity. However, further research is necessary to thoroughly determine the value of this group of drugs. PMID- 26557757 TI - Malignant transformation of calcifying cystic odontogenic tumour - a review of literature. AB - Calcifying cystic odontogenic tumour (CCOT) has been classified as an odontogenic tumour. Ghost cell odontogenic carcinoma (GCOC) is the malignant counterpart of CCOT. This paper aims to review the literature regarding malignant transformation of CCOT. A literature search was done via the National Library of Medicine PubMed interface, searching for articles relating to malignant transformation of CCOT. From these articles, references were obtained, and from their references lists, pertinent secondary references were also identified and acquired. After reviewing the literature, we found 26 cases of GCOC which developed from CCOT. Malignant transformation of CCOT was seen more commonly in the maxilla. Histologically, changes such as increased nuclear/cytoplasmic ratio, atypical mitotic figures have been reported after malignant transformation. Immunohistochemical analysis has shown an increased expression of ki-67 and p53 in tumour cells. Malignant transformation of CCOT, although rare, mostly takes place in recurrent and long standing cases. PMID- 26557756 TI - Familial syndromes associated with neuroendocrine tumours. AB - Neuroendocrine tumours may be associated with familial syndromes. At least eight inherited syndromes predisposing to endocrine neoplasia have been identified. Two of these are considered to be major factors predisposing to benign and malignant endocrine tumours, designated multiple endocrine neoplasia type 1 and type 2 (MEN1 and MEN2). Five other autosomal dominant diseases show more heterogeneous clinical patterns, such as the Carney complex, hyperparathyroidism-jaw tumour syndrome, Von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1) and tuberous sclerosis. The molecular and cellular interactions underlying the development of most endocrine cells and related organs represent one of the more complex pathways not yet to be deciphered. Almost all endocrine cells are derived from the endoderm and neuroectoderm. It is suggested that within the first few weeks of human development there are complex interactions between, firstly, the major genes involved in the initiation of progenitor-cell differentiation, secondly, factors secreted by the surrounding mesenchyme, and thirdly, a series of genes controlling cell differentiation, proliferation and migration. Together these represent a formula for the harmonious development of endocrine glands and tissue. PMID- 26557758 TI - Cell-based Hyper-interleukin 6 or Hyper-interleukin 11 secreting vaccines combined with low dose cyclophosphamide in an orthotopic murine prostate cancer model. AB - BACKGROUND: Cell based vaccines encoding Hyper-IL-6 (H6) and Hyper-IL-11 (H11) present high activity in murine melanoma and renal cancer model. We evaluated the efficacy of cellular vaccines modified with H6 or H11 combined with cyclophosphamide in orthotopic murine prostate cancer model. MATERIAL AND METHODS: TRAMP cells were transduced with H6 and H11 cDNA (TRAMP-H6 and TRAMP H11). An orthotopic TRAMP model based on the implantation of TRAMP cells into the dorsolateral lobe of the prostate of C57BL6/J mice was employed. The efficacy of TRAMP-H6 and TRAMP-H11 vaccines evaluated in the therapeutic setting was compared with the TRAMP cells modified with a mock transduced E1-deleted adenoviral vector (TRAMP-AdV) and non-modified irradiated TRAMP cells (TRAMP IRR) in relation to naive (non-immunized) mice. In the next experimental groups mice vaccinated with TRAMP-H6 and TRAMP-H11 received cyclophosphamide (CY). Detection of immune cells in the spleen in mice receiving vaccines combined with CY was evaluated. RESULTS: Modification of TRAMP cells with H6 increased the efficacy of TRAMP-based whole cell vaccine. The highest response rate was observed in mice receiving TRAMP-H6 alone and combined with CY. Vaccination with TRAMP-H6 alone and combined with CY and TRAMP H11 combined with CY extended median OS of mice bearing orthotopic TRAMP tumors in therapeutic setting. Low dose CY administered alone demonstrated some antitumor activity in employed model. TRAMP-H6 or TRAMP-H11 combined with CY strongly augmented generation of CD8+, CD4+ T lymphocytes and memory T cells. Immunization with TRAMP combined with or without CY suppressed generation of T regulatory cells. CONSLUSIONS: Prostate cancer vaccines modified with H6 or H11 induce prostate tumour regression and increase mice survival by stimulating the immune system. Cyclophosphamide added to modified TRAMP vaccines demonstrated clinical benefit of treated mice and enhanced anti-tumour immune response. PMID- 26557759 TI - Expression of Th17 cell population regulatory cytokines in laryngeal carcinoma - Preliminary study. AB - AIM OF THE STUDY: Aim of the study was to evaluate the potential role of regulatory and proinflammatory cytokines IL-23 and IL-17 as Th17 lymphocyte activity markers in relation to invasiveness in laryngeal cancer. MATERIAL AND METHODS: The immunological analysis was conducted in 50 patients treated for squamous cell laryngeal carcinoma and 30 healthy volunteers as controls. The levels of IL-23 and IL-17 in supernatants of purified peripheral blood mononuclear cell cultures were determined by using the enzyme-linked immunosorbent assay (ELISA). The clinicomorphological criteria included pTNM, stage, G, and the total tumour front grading (TFG) score. RESULTS: Our data demonstrated higher concentrations of IL-23 in patients as compared to controls (p = 0.0001). No statistical difference for IL-17 in these groups was observed. Our study revealed significant dependences in IL-23 expression on pT (p = 0.04), histological differentiation (p = 0.04), and TFG total score (p = 0.02). Advanced tumours (pT3-pT4) with higher grade (G2-G3) and higher invasiveness (> 14 TFG points) were characterised by elevated IL-23 levels in PBMC supernatants. Our data did not indicate a relationship between cytokine levels and three- and five year survival. However, a tendency towards lower content of IL-23 in PBMC cultures in patients who lived longer than five years after treatment was noted. The relationships between IL-17 level in PBMC cultures and clinicomorphological and prognostic parameters have not been disclosed. CONCLUSIONS: The results of this study suggest the importance of regulatory cytokine IL-23 in determining the aggressive potential of laryngeal carcinomas. PMID- 26557760 TI - MicroRNA-7 enhances cytotoxicity induced by gefitinib in non-small cell lung cancer via inhibiting the EGFR and IGF1R signalling pathways. AB - Gefitinib is a tyrosine kinase inhibitor that has been used for the treatment of non-small-cell lung carcinoma (NSCLC). The ability of miR-7 to enhance gefitinib induced cytotoxicity in NSCLC cells was evaluated in this study. We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth. G0/G1 cell cycle arrest and cell apoptosis were increased after the treatment of gefitinib coupled with miR-7 transfection. In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased. Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs. PMID- 26557761 TI - ERCC1 and RRM1 as a predictive parameter for non-small cell lung, ovarian or pancreas cancer treated with cisplatin and/or gemcitabine. AB - BACKGROUND: We aimed to investigate the impact of RRM1 and ERCC1 expression on response to cisplatin and/or gemcitabine chemotherapy in patients with lung, ovarian or pancreatic cancer. MATERIAL AND METHODS: Patients with lung, ovarian or pancreatic cancer, who used cisplatin and/or gemcitabine therapy were included; hospital files were examined and RRM1 and ERCC1 expression were evaluated with an immunohistochemical method on tissue cross sections from paraffin blocks of the tumour. RESULTS: Out of 89 patients, 51%, 30% and 19% had lung, ovarian and pancreatic cancer, respectively. The response rates to the therapy in patients with lung and ovarian cancer having low ERCC1 expression were 62% and 90%, respectively (p = 0.028 and p = 0.044, respectively). No significant association was found between ERCC1 expression and response to therapy in patients with pancreatic cancer (p = 0.354). Therapeutic response rates in patients with lung and pancreatic cancer with low RRM1 expression were 60% and 82%, respectively. Survival rates were higher in patients with lung cancer in which ERCC1 and RRM1 expressions were low. Median survival duration in patients with ovarian cancer showing low ERCC1 and RRM1 expressions was longer than that seen in patients with high expressions. Although no significant correlation was found between ERCC1 and the survival in ovarian cancer (p = 0.183), there was a significant correlation between RRM1 expression and survival in patients with pancreatic cancer (p = 0.005). CONCLUSIONS: Our results suggest a predictive value of ERCC1 in lung and ovarian cancers, and also RRM1 in lung and pancreatic cancers. PMID- 26557762 TI - Multicentre, Prospective Observational Study of Pegfilgrastim Primary Prophylaxis in Patients at High Risk of Febrile Neutropenia in Poland: PROFIL Study. AB - AIM OF THE STUDY: PROFIL was a prospective observational study conducted to investigate physicians' evaluation of febrile neutropenia (FN) risk and reasons for giving pegfilgrastim primary prophylaxis (PP) in routine clinical practice in Poland. MATERIAL AND METHODS: Adult cancer patients treated with chemotherapy (CT), assessed by investigators as having high overall FN risk, and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010. Investigators assessed FN risk of the CT regimen, individual risk factors, and overall FN risk, and were asked to provide the most important reasons for providing pegfilgrastim PP. Investigator-assessed CT FN risk was compared with guideline classification. RESULTS: Data were analysed from 1006 breast, ovarian, and lung cancer, and non Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease; these were consistent across tumour types and treatment intent. The investigators generally assessed high CT FN risk in agreement with guideline classification. Febrile neutropenia occurred in 4% of patients, most commonly in HL, NHL, and patients with advanced disease. CONCLUSIONS: High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Poland. PMID- 26557763 TI - The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women. AB - AIM OF THE STUDY: Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status. MATERIAL AND METHODS: Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. RESULTS: Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (-) tumours. CONCLUSIONS: Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics. PMID- 26557764 TI - The Spectrum of Malignancies among Adult HIV Cohort in Poland between 1995 and 2012: A Retrospective Analysis of 288 Cases. AB - THE AIM OF THE STUDY: The aim of the study was to evaluate the spectrum of AIDS defining malignancies (ADMs) and non-AIDS-defining malignancies (NADMs) in HIV infected patients in Poland. MATERIAL AND METHODS: A retrospective observational study was conducted among HIV-infected adult patients who developed a malignancy between 1995 and 2012 in a Polish cohort. Malignancies were divided into ADMs and NADMs. Non-AIDS-defining malignancies were further categorised as virus-related (NADMs-VR) and unrelated (NADMs-VUR). Epidemiological data was analysed according to demographic data, medical history, and HIV-related information. Results were analysed by OR, EPITools package parameters and Fisher's exact test. RESULTS: In this study 288 malignancies were discovered. The mean age at diagnosis was 41.25 years (IQR20-81); for ADMs 38.05 years, and for NADMs-VURs 46.42 years; 72.22% were male, 40.28% were co-infected with HCV. The risk behaviours were: 37.85% IDU, 33.33% MSM, and 24.31% heterosexual. Mean CD4+ at the diagnosis was 282 cells/mm(3) (for ADMs 232 and for NADMs-VUR 395). Average duration of HIV infection at diagnosis was 5.69 years. There were 159 (55.2%) ADMs and 129 (44.8%) NADMs, among whom 58 (44.96%) NADMs-VR and 71 (55.04%) NADMs-VUR. The most frequent malignancies were: NHL (n = 76; 26.39%), KS (n = 49; 17.01%), ICC (n = 34; 11.81%), HD (n = 23; 7.99%), lung cancer (n = 18; 6.25%) and HCC (n = 14; 4.86%). The amount of NADMs, NADMs-VURs in particular, is increasing at present. Male gender (OR = 1.889; 95% CI: 1.104-3.233; p = 0.024), advanced age: 50-60 years (OR = 3.022; 95% CI: 1.359-6.720; p = 0.01) and >= 60 years (OR = 15.111; 95% CI: 3.122-73.151; p < 0.001), longer duration of HIV-infection and successful HAART (OR = 2.769; 95% CI: 1.675-4.577; p = 0) were independent predictors of NADMs overall, respectively. CONCLUSIONS: In a Polish cohort NHL was the most frequent malignancy among ADMs, whereas HD was the most frequent among NADMs. Increased incidence of NADMs appearing in elderly men with longer duration of HIV-infection and with better virological and immunological control was confirmed. As HIV-infected individuals live longer, better screening strategies, especially for NADMs-VUR, are needed. The spectrum of cancer diagnoses in Poland currently does not appear dissimilar to that observed in other European populations. PMID- 26557765 TI - Radiation enhancing effects of sanazole and gemcitabine in hypoxic breast and cervical cancer cells in vitro. AB - AIM OF THE STUDY: Sanazole and gemcitabine have been proven clinically as hypoxic cell radiosensitisers. This study was conducted to determine the radiation enhancing effects of sanazole and gemcitabine when administered together at relevant concentrations into hypoxic human MCF-7 and HeLa cells. MATERIAL AND METHODS: A 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Cell surviving fractions were determined by the standard in vitro colony formation assay. RESULTS: The cell colony formation assay indicated that the radiosensitivity of hypoxic MCF-7 and HeLa cells was enhanced by sanazole or gemcitabine. The combination of the two drugs displayed significant radiation enhancing effects at the irradiation doses of 6, 8, and 10 Gy in both cell lines, which were arrested in the S phase. CONCLUSIONS: This study indicated that the co-administration of the two drugs may result in a beneficial gain in radio-therapy for hypoxic breast cancer and cervical cancer. PMID- 26557766 TI - Haematogenous muscular metastasis of non-small cell lung cancer in F-18 fluorodeoxyglucose positron emission tomography/computed tomography. AB - AIM OF THE STUDY: F-18 FDG PET/CT is the most effective method for demonstrating extrapulmonary metastases of lung cancer. The aim of this study is to investigate the level of muscular metastasis of non-small-cell lung carcinoma (NSCLC) in F-18 FDG PET/CT and to demonstrate the characteristics of this special group of patients. MATERIAL AND METHODS: A total of 1150 patients with the diagnosis of NSCLC, who were referred for F-18 FDG PET/CT, were included into the study. Among these patients, the findings of 13 who were shown to have muscle metastases were studied. RESULTS: In the retrospective analysis of the patients, 13 patients (12 male, 1 female; mean: 59 +/-7 years old) were found to have haematogenous (excluding local invasion) muscular metastases of NSCLC using F-18 FDG PET/CT. Two of the 13 patients had only muscular metastases (one patient isolated, one patient two foci). The other 11 patients had additional distant metastases in six metastatic sites (bone in 7 patients, distant lymph node in 6, adrenal gland in 5, contralateral lung in 3, liver in 1, and brain metastasis in 1 patient). Five patients died during the mean 11 +/-8 months follow up. CONCLUSIONS: Muscular metastasis is not a rare condition, especially in F-18 FDG PET/CT examinations, and is frequently associated with additional distant metastases. PMID- 26557767 TI - Osteosarcoma of the larynx. AB - Malignant neoplasms of the larynx are divided into epithelial and non-epithelial. Non-epithelial neoplasms include, among others, mesenchymal chondrosarcomas and osteosarcomas. Few cases of laryngeal osteosarcomas described in the literature were usually treated by surgery without the need to use adjuvant radio- or chemotherapy. Few authors propose the initial application of radiotherapy or high dose chemotherapy. Our study presents a very rare case of a woman treated due to laryngeal osteosarcoma. We have also presented diagnostic difficulties preceding a decision to perform radical surgery. The patient had been eligible for radical surgical treatment, even though there were no features of malignancy in a histopathological examination of the biopsy material. Complete laryngectomy was carried out without the surgery of the cervical lymphatic system. Laryngeal osteosarcoma was diagnosed based on the postoperative histopathological examination using vimentin and Ki67. The patient remains under the care of the Otolaryngology and Laryngological Oncology Department and Oncology Centre in Bydgoszcz. There were no reports on local recurrence or distant metastases during regular check-ups. PMID- 26557768 TI - Letter to the editor concerning first-line therapy with afatinib - an irreversible EGFR TKI and overall survival of NSCLC patients with EGFR gene mutations. PMID- 26557769 TI - Paratesticular rhabdomyosarcoma of a young adult. PMID- 26557770 TI - Use of high-dose oxycodone hydrochloride in patients with visceral and neuropathic pain. PMID- 26557771 TI - The role of Reg IV in colorectal cancer, as a potential therapeutic target. AB - Regenerating islet-derived family, member 4 (Reg IV), a member of the Reg gene family, has been reported to be overexpressed in gastrointestinal tract cancers. Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis. Reg IV activates the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer and increases expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), which are associated with the inhibition of apoptosis, results in mitogenic signaling in colon cancer cells, increase cell proliferation, metastasis and decreased apoptosis. Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD). These studies may lead to novel therapeutic strategies for cancers expressing Reg IV. Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect. This review summaries current knowledge of the expression and roles of Reg IV in human colorectal cancer, describes the possible signaling pathway which Reg IV activates, and discusses the relevance of Reg IV as a potential therapeutic target for cancer treatment. PMID- 26557772 TI - The role of Snail1 transcription factor in colorectal cancer progression and metastasis. AB - Snail1 is a zinc-finger transcription factor, which plays a role in colorectal cancer development by silencing E-cadherin expression and inducing epithelialmesenchymal transition (EMT). During EMT tumour cells acquire a mesenchymal phenotype that is responsible for their invasive activities. Consequently, Snail1 expression in colorectal cancer is usually associated with progression and metastasis. Some studies revealed that about 77% of colon cancer samples display Snail1 immunoreactivity both in activated fibroblasts and in carcinoma cells that have undergone EMT. Therefore, expression of this factor in the stroma may indicate how many cells possess the abilities to escape from the primary tumour mass, invade the basal lamina and colonise distant target organs. Blocking snail proteins activity has the potential to avert cancer cell metastasis by interfering with such cellular processes as remodelling of the actin cytoskeleton, migration and invasion, which are clearly associated with the aggressive phenotype of the disease. Moreover, the link between factors from the snail family and cancer stem cells suggests that inhibitory agents may also prove their potency as inhibitors of cancer recurrence. PMID- 26557773 TI - Noble metals in oncology. AB - Worldwide research groups are searching for anticancer compounds, many of them are organometalic complexes having platinum group metals as their active centers. Most commonly used cytostatics from this group are cisplatin, carboplatin and oxaliplatin. Cisplatin was used fot the first time in 1978, from this time many platinum derivatives were created. In this review we present biological properties and probable future clinical use of platinum, gold, silver, iridium and ruthenium derivatives. Gold derivative Auranofin has been studied extensively. Action of silver nanoparticles on different cell lines was analysed. Iridium isotopes are commonly used in brachyterapy. Ruthenium compound new anti tumour metastasis inhibitor (NAMI-A) is used in managing lung cancer metastases. Electroporation of another ruthenium based compound KP1339 was also studied. Most of described complexes have antiproliferative and proapoptotic properties. Further studies need to be made. Nevertheless noble metal based chemotherapheutics and compounds seem to be an interesting direction of research. PMID- 26557774 TI - Analysis of sequence variants in the 3'UTR of CDKN2A gene in melanoma patients. AB - BACKGROUND: The 3'UTR region plays a crucial role in regulating gene expression at posttranscriptional levels. Any changes in sequence in this region can cause numerous pathologies and can also lead to tumour development. The most common changes reported in in the CDKN2A gene are the 148Ala/Thr in exon 2 and 500C>G and 540C>T in the 3'UTR region. They are suspected of having a great impact on cancer progression. Since the role of these sequence variants in the Polish population in the development of melanoma has not been confirmed, the importance of 3'UTR polymorphisms in the regulation of gene expression was tested. MATERIAL AND METHODS: First, genetic analysis in a group of 285 melanoma patients was performed and the obtained results were correlated with the clinical course of melanoma. Then vectors carrying 3'UTR sequence variants were prepared and the level expression of the reported gene was measured. RESULTS: Within this study no correlation between the presence of 148Ala/Thr polymorphism and cancer in the family was observed. There was a correlation between the presence of this polymorphism and breast cancer and melanoma in the same patient. There was no correlation between 500C>G polymorphism and tumour localisation, age of diagnosis, and type of cancer in patients' family, but a correlation between the percentage of patients dying and the 500C>G variant was observed. CONCLUSION: The results of functional tests indicated that the presence of polymorphism in the 3'UTR region of the CDKN2A gene resulted in changes in the level of reporter gene expression. PMID- 26557775 TI - The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial. AB - AIM OF THE STUDY: The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres. MATERIAL AND METHODS: Patients with untreated or previously treated Stage IIIC/IV BRAFV600 mutation-positive melanoma were treated with oral vemurafenib in an initial dose of 960 mg twice daily. Assessments for safety and efficacy were made every 28 days. For the survival analysis the Kaplan-Meier estimator was used with the log-rank tests for bivariate comparisons. RESULTS: In total, 75 Polish patients were enrolled in the safety study across four centres. At data cut-off, 28 patients died (37%), mainly (26) due to disease progression; 33 (44%) patients continued vemurafenib after disease progression. The objective response rate was 46%, including two patients with a complete response and 29 with a partial response. Median progression-free survival was 7.4 months. The one year overall survival rate was 61.9% (median overall survival was not reached). Seventy-three (97.3%) patients reported adverse events (AEs), and grade 3-5 toxicity was reported in 49.4% (37) patients. The most common AEs were: skin lesions (including rash and photosensitivity), arthralgia, and fatigue. CONCLUSIONS: The overall safety profile and response rate of vemurafenib were comparable to those reported in previous studies of this drug. Our study confirmed the value of well-established prognostic features for overall survival, such as initial LDH (lactate dehydrogenase) level and AJCC staging. PMID- 26557776 TI - Overall survival and disease-free survival in breast cancer patients treated at the Oncology Centre in Bydgoszcz - analysis of more than six years of follow-up. AB - AIM OF THE STUDY: Malignant breast tumours are the largest oncological problem in the developed world. In the recent years the number of new diagnoses has exceeded 16,500 per year. Published data regarding far-distant results of breast cancer treatment that take under consideration the provincial division of the country may not be representative of the therapeutic effects achieved in specific oncological centres. The goal of this article is to analyse far-distant therapeutic results in breast cancer patients treated at the Oncology Centre in Bydgoszcz in 2006. They were compared with data available for Kujawsko-Pomorskie Voivodeship and with all-Poland results. MATERIAL AND METHODS: A cohort of 667 breast cancer patients at Bydgoszcz Oncology Centre between Jan 1 and Dec 31, 2006 was studied. The majority of the studied group were patients in stage I (26.2%) and II (48.3%) according to the TNM staging system, 17.5% were in stage III, and 6.4% in stage IV. The 5-year survival and 5-year disease-free survival rates were calculated. Median observation time was 79 months. RESULTS: A total of 148 patients (22.2%) suffered a relapse. There were 168 (25.2%) deaths caused by primary disease. The 5-year survival probability was 0.761 +/-0.017 and the five year disease-free survival probability was 0.807 +/-0.016. Median survival time was 76.4 months, and median disease-free survival was 19.4 months. CONCLUSIONS: The five-year survival probability for breast cancer patients undergoing treatment at Bydgoszcz Oncology Centre was higher than all-Poland median five year survival probability. The observation needs to be continued and should include the assessment of treatment in subsequent time periods. PMID- 26557777 TI - Comparative study of various subpopulations of cytotoxic cells in blood and ascites from patients with ovarian carcinoma. AB - AIM OF THE STUDY: A number of observations have indicated that the immune system plays a significant role in patients with epithelial ovarian cancer (EOC). In cases of EOC, the prognostic significance of tumour infiltrating lymphocytes has not been clearly explained yet. The aim is to determine the phenotype and activation molecules of cytotoxic T cell and NK cell subpopulations and to compare their representation in malignant ascites and peripheral blood in patients with ovarian cancer. MATERIAL AND METHODS: Cytotoxic cells taken from blood samples of the cubital vein and malignant ascites were obtained from 53 patients with EOC. Their surface and activation characteristics were determined by means of a flow cytometer. Immunophenotype multiparametric analysis of peripheral blood lymphocytes (PBLs) and tumour infiltrating lymphocytes (TILs) was carried out. RESULTS: CD3(+) T lymphocytes were the main population of TILs (75.9%) and PBLs (70.9%). The number of activating T cells was significantly higher in TILs: CD3(+)/69(+) 6.7% vs. 0.8% (p < 0.001). The representation of (CD3(-)/16(+)56(+)) NK cells in TILs was significantly higher: 11.0% vs. 5.6% (p = 0.041); likewise CD56(bright) and CD-56(bright) from CD56(+) cells were higher in TILs (both p < 0.001). The activation receptor NKG2D was present in 45.1% of TILs vs. 32.3% of PBLs (p = 0.034), but we did not find a significant difference in the numbers of CD56(+)/NKG2D(+) in TILs and PBLs. CONCLUSIONS: These results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (ascites/PBLs). The knowledge of phenotype and functions of effector cells is the basic precondition for understanding the anti tumour immune response. PMID- 26557778 TI - The influence of matrix metalloproteinase-2, -9, and -12 promoter polymorphisms on Iranian patients with oesophageal squamous cell carcinoma. AB - AIM OF THE STUDY: Matrix metalloproteinases (MMPs) are a zinc-dependant endopeptidase family that can degrade extracellular matrix components. Their dysregulation has been proven in several diseases, including cancer. Genetic variations in MMP promoter regions can alter their expression. The aim of the present study is to investigate the correlation of MMP-2 (-1306C/T), MMP-9 ( 1562C/T), and MMP-12 (-82A/G) single nucleotide polymorphisms (SNPs) with oesophageal squamous cell carcinoma (ESCC) initiation and progression susceptibility in Iranian patients. MATERIAL AND METHODS: MMP-2 (-1306C/T), MMP-9 (-1562C/T), and MMP-12 (-82A/G) SNPs were detected using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique in 70 patients and 60 healthy controls. The genotypes and allele distributions were statistically compared in patients and controls. The correlation of MMP-2 ( 1306C/T) and MMP-9 (-1562C/T) polymorphisms with clinicopathological features were investigated in 53 patients. RESULTS: No statistically significant differences were observed in genotype and allele frequencies of MMP-2 (-1306C/T) and MMP-9 (-1562C/T) between patients and controls (p > 0.05). In addition, no relevance was observed in MMP-2 (-1306C/T) and MMP-9 (-1562C/T) SNPs and clinicopathological features. There was no nucleotide variation in MMP-12 (-82) in the case and control groups. CONCLUSIONS: This study indicates that these three SNPs may have no significant association in ESCC risk in Iranian patients. PMID- 26557779 TI - The effect of Lactobacillus casei extract on cervical cancer cell lines. AB - AIM OF THE STUDY: Lactobacillus casei (L. casei) has been shown to inhibit the proliferation of several types of cancer in vivo, but its effect on cervical cells has not been reported. We incubated cells of the human cervical cell lines Caski and HeLa with extracts of L. casei and investigated its effects on the growth of the cells and possible synergy with anticancer drugs. MATERIAL AND METHODS: Cell-free extracts of L. casei were prepared and purified. Cultures of Caski and HeLa cells adhering to tissue culture plates were treated with L. casei extract. The effects of L. casei extract on the growth of cancer cells and its possible synergy with anti-cancer drugs in cervical cancer cell lines were investigated. The cells were treated with L. casei extract alone, anti-cancer drugs alone [doxorubicin, paclitaxel, 5-fluorouracil (5-FU), and cisplatin], or L. casei extract plus anti-cancer drugs. RESULTS: L. casei extract had no significant effect on the growth rate of the two cell lines. Anti-cancer drugs alone induced growth inhibition, but there was no synergistic effect of L. casei extract on growth inhibition. CONCLUSIONS: L. casei extract does not have a potent effect on the viability of cervical cancer cells in vitro. In addition, L. casei extract has no synergistic effect on the inhibition of growth of cancer cells in the presence of anti-cancer drugs. PMID- 26557781 TI - Clinical observation of docetaxel or gemcitabine combined with cisplatin in the chemotherapy after surgery for stage II-III non-small cell lung cancer. AB - AIM OF THE STUDY: This study aimed to compare the efficacy and toxicity of docetaxel combined with cisplatin (DP) and gemcitabine combined with cisplatin (GP) in postoperative chemotherapy after surgery of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 92 patients diagnosed with NSCLC after surgery were enrolled, and they were treated with DP (DP group) and GP (GP group). The efficacy and toxicity of the medications were then compared. RESULTS: Approximately 92.4% (85 out of 92) of the patients received chemotherapy for more than three weeks. In the DP and GP groups, the incidence rates of grade III-IV thrombocytopenia were 24.4% and 6.38%, respectively, whereas the incidence rates of alopecia were 88.9% and 25.5%, respectively. The difference between the two groups was statistically significant (p < 0.05). Disease-free survival rates in DP group in one and two years were 76.5% and 50.47%, respectively, whereas in the GP group they were 77.8% and 49.52%, respectively. No significant difference was observed between the two groups (p > 0.05). CONCLUSIONS: These results showed similar disease-free survival rates of DP and GP therapies in one and two years after surgery for NSCLC. However, the DP group exhibited higher incidence rates of grade III-IV thrombocytopenia and alopecia than the GP group. Therefore, we should select a specific treatment for each patient according to individual differences. PMID- 26557780 TI - The rationale for HPV-related oropharyngeal cancer de-escalation treatment strategies. AB - The treatment paradigms for head and neck squamous cell cancer (HNSCC) are changing due to the emergence of human papillomavirus-associated tumors (HPV related), possessing distinct molecular profiles and responses to therapy. Retrospective studies have suggested that HPV-related HNSCCs are more frequently cured than those caused by tobacco. Current clinical trials focus on the reduction of treatment-related toxicity and the development of HPV-targeted therapies. New treatment strategies include: 1) dose reduction of radiotherapy, 2) the use of cetuximab instead of cisplatin for chemo-radiation 3) less invasive surgical options, i.e. trans-oral robotic surgery and trans-oral laser microlaryngoscopy, and 4) more specific treatment attempts, including immunotherapeutic strategies, thanks to increasing comprehension of the molecular background of HPV-related HNSCC. Whereas recently published data shed light on immune mechanisms, other studies have focused on specific vaccination against HPV related HNSCC. A crucial problem is patient selection to the chosen bias. Truly HPV-related cancers (p16-positive and HPV DNA-positive) with biomarkers for good response to therapy could be included in randomized trials aiming for less severe and better tailored therapy. PMID- 26557782 TI - Evaluation of efficacy and safety of robotic stereotactic body radiosurgery and hypofractionated stereotactic radiotherapy for vertebral metastases. AB - AIM OF THE STUDY: The purpose of this study was to evaluate the efficacy and safety of applying CyberKnife (CK) radiosurgery in patients with spinal metastases. MATERIAL AND METHODS: Twenty-eight patients with vertebral metastases treated using the CK system were included in the study. Eleven patients suffered from pain, and in 1 case neurological symptoms were observed. The remaining patients were free from clinical symptoms of metastatic disease. The doses applied ranged between 8 and 40 Gy delivered in 4 fractions of 8-15 Gy. RESULTS: In the first follow-up evaluation (mean 4.5 months after the treatment), pain was stable in 5 of 8 evaluable cases and in 3 regression occurred. The last follow-up examination (mean 11 months after stereotactic radiosurgery) revealed stable ailments in 3 of 6 evaluable cases, improvement in 3 and new complaints in another 4 patients. In 17 patients imaging studies were conducted after a mean time of 11 months after CK treatment. Stabilization was confirmed in 11, regression in 4 and progression in 2 cases. Median overall survival was 20.6 months. Median progression-free survival was 12.6 months. No side effects attributable to the treatment were observed, but during follow-up transient or permanent deterioration in neurological status as a consequence of disease progression was diagnosed in 4 patients. Delivery time of a single fraction ranged between 0.5 and 1.5 hours. CONCLUSIONS: Robotic stereotactic radiosurgery as part of multimodality therapy for metastatic spinal tumours is safe and effective. Because of long irradiation times, this kind of treatment is not suitable for patients in poor general condition. PMID- 26557783 TI - Understanding the purpose of treatment and expectations in patients with inoperable lung cancer treated with palliative chemotherapy. AB - AIM OF THE STUDY: Informing cancer patients about various types of treatment and their adverse effects and communicating negative information is an important element of diagnostic and therapeutic procedures. Understanding the purpose of treatment and expectations, and socio-demographic factors in patients undergoing palliative chemotherapy because of lung cancer. MATERIAL AND METHODS: The study included 100 patients with lung cancer at the age of 40-80 years (mean 63.1) in the Oncology Center in Bydgoszcz in 2013-2014. The diagnostic survey method with the author's questionnaire was used. RESULTS: Forty-one percent of patients were convinced that the purpose of chemotherapy is to cure the disease. Both inhabitants of small towns (population below 50 thousand) and large villages (p = 0.09) were similarly convinced about the effectiveness of chemotherapy. Seventy three percent of inhabitants of small towns and 79% of country dwellers (p = 0.005) thought that chemotherapy is aimed at improving the quality of life. Patients with very good economic conditions responded that chemotherapy is designed to improve the quality of life more often than those with good and bad economic conditions, 90%, 88% and 60%, respectively (p = 0.001). With the increase in population the number of people who claimed that palliative chemotherapy prolongs their life increased, 71%, 77% and 90%, respectively (p = 0.03). CONCLUSIONS: The knowledge of patients with lung cancer about palliative chemotherapy is insufficient. Almost half of them do not understand the purpose of treatment and hope that chemotherapy will cure them of the disease. Most patients know that the aim of chemotherapy is to alleviate symptoms and improve quality of life and prolong their life. Half of the patients want to obtain information on treatment and half of them about life expectancy. Almost half of the patients feel stress and anxiety towards chemotherapy. Most patients do not use the help of a psychologist and do not feel such a need. PMID- 26557784 TI - Changing incidence of esophageal cancer among white women: analysis of SEER data (1992-2010). AB - AIM OF THE STUDY: To analyse trends in the incidence rates of adenocarcinoma and squamous cell carcinoma of the oesophagus (ACE and SCC, respectively) in white women between 1992 and 2010. MATERIAL AND METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER program to identify cases of esophageal cancer). Age adjusted incidence rates (IR) were calculated for ACE and SCC for two different time periods (1992-1996 and 2006-2010) and stratified by age, stage, and histologic type. We used joinpoint analysis to detect changes in rates between 1992 and 2010. RESULTS: Between the time periods 1992-1996 and 2006 2010, the age-adjusted incidence rates for SCC in white women decreased from 1.2/100,000 to 0.8/100,000 personyears, and for ACE it increased from 0.5/100,000 to 0.7/100,000 personyears. Similar to white men, the increase in the incidence of ACE was consistent for all stages and all age groups in white women. However, it was most pronounced in women aged 45-59 years, where the incidence of ACE (0.9/100,000 person-years) in 2006-2010 exceeded the incidence of SCC (0.6/100,000 person-years). On joinpoint regression analysis, an inflection point was seen in 1999 for ACE, indicating a slower rate of increase for ACE after 1999 (annual percentage change of 8.00 before 1999 vs. 0.88 starting in 1999). CONCLUSIONS: The incidence of ACE is increasing in white women, irrespective of age or stage. Indeed, ACE is now more common than SCC in white women between 45 and 59 years of age. PMID- 26557785 TI - Photodynamic diagnosis - current tool in diagnosis of carcinoma in situ of the urinary bladder. PMID- 26557786 TI - Multiple endocrine neoplasia and primary hyperparathyroidism - practical approach. PMID- 26557787 TI - Examining the influence of treatment preferences on attrition, adherence and outcomes: a protocol for a two-stage partially randomized trial. AB - BACKGROUND: Empirical evidence pertaining to the influence of treatment preferences on attrition, adherence and outcomes in intervention evaluation trials is inconsistent. The inconsistency can be explained by the method used for allocating treatment and measuring preferences. The current methodological study is designed to address these factors by implementing the two-stage partially randomized or preference trial design, and administering a validated measure to assess participants' preferences for the treatments under evaluation. It aims to compare attrition, adherence and outcomes for participants allocated randomly or by preference to treatment. The study is in its final stages of data collection; its protocol is presented in this paper. METHODS/DESIGN: A partially randomized clinical or preference trial is used. Eligible participants are randomized to two trial arms. First is the random arm involving random assignment to treatments, and second is the preference arm involving allocation to the chosen treatment. Participants with chronic insomnia are targeted. Two behavioral treatments are offered, stimulus control therapy and sleep restriction therapy, in the same format (small group) and dose (two sessions given over a 4-week period). A participant log is used to collect data on attrition. Adherence is evaluated in terms of exposure and enactment of treatment. Sleep-related outcomes (sleep parameters and perceived insomnia severity) are measured at pretest, posttest, 6 and 12 month follow-up. Treatment preferences, adherence and outcomes are assessed with reliable and valid measures. DISCUSSION: The advantages and limitations of the preference trial design are highlighted. The challenges in implementing the trial are discussed relative to the distribution of participants in the groups defined by treatment received and method of treatment allocation. TRIAL REGISTRATION: ClinicalTrials.gov Registry NCT02513017. PMID- 26557788 TI - Haemodialysis work environment contributors to job satisfaction and stress: a sequential mixed methods study. AB - BACKGROUND: Haemodialysis nurses form long term relationships with patients in a technologically complex work environment. Previous studies have highlighted that haemodialysis nurses face stressors related to the nature of their work and also their work environments leading to reported high levels of burnout. Using Kanters (1997) Structural Empowerment Theory as a guiding framework, the aim of this study was to explore the factors contributing to satisfaction with the work environment, job satisfaction, job stress and burnout in haemodialysis nurses. METHODS: Using a sequential mixed-methods design, the first phase involved an on line survey comprising demographic and work characteristics, Brisbane Practice Environment Measure (B-PEM), Index of Work Satisfaction (IWS), Nursing Stress Scale (NSS) and the Maslach Burnout Inventory (MBI). The second phase involved conducting eight semi-structured interviews with data thematically analyzed. RESULTS: From the 417 nurses surveyed the majority were female (90.9 %), aged over 41 years of age (74.3 %), and 47.4 % had worked in haemodialysis for more than 10 years. Overall the work environment was perceived positively and there was a moderate level of job satisfaction. However levels of stress and emotional exhaustion (burnout) were high. Two themes, ability to care and feeling successful as a nurse, provided clarity to the level of job satisfaction found in phase 1. While two further themes, patients as quasi-family and intense working teams, explained why working as a haemodialysis nurse was both satisfying and stressful. CONCLUSIONS: Nurse managers can use these results to identify issues being experienced by haemodialysis nurses working in the unit they are supervising. PMID- 26557789 TI - Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population. AB - BACKGROUND: Venous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients. METHODS: This long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient's history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 % confidence interval (CI). RESULTS: Our results revealed that FV Leiden (OR 6.7; 95 % CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 % CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 % CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 % CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls. CONCLUSION: Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT. PMID- 26557790 TI - Psychoactive Substances Bill and Act of New Zealand: A Chance to Engage Undergraduate Scientists with Society using a Transfer Learning Paradigm. AB - Our aim was to develop a teaching paradigm that connected undergraduate's neuropharmacological/toxicological knowledge to that of government policy. One goal of undergraduate education should be to help develop scientists that can use their scientific knowledge to critique government policy. There is little research, however, on whether democratization of science occurs: nor how to achieve this. Our work focused on a semi-structured workshop designed around the Psychoactive Substances Bill (PSB). Third year science students were given a questionnaire that was designed to address whether participating in the workshop enhanced their understanding of the PSB and its relationship to their established knowledge (i.e., transfer learning). Furthermore, whether they felt that they had enough expertise to consider making a submission (i.e., societal engagement). Results showed that the students appreciated the opportunity to explore potential application of their knowledge and delve into a socio-scientific issue. However, our findings suggested they felt uncomfortable discussing their ideas outside the classroom: nor, did they identify themselves as having sufficient knowledge to contribute to a submission. In conclusion, this study highlights two points. First, that discussion based transfer learning can be used in the tertiary sector and students value the opportunity to apply their knowledge to socio-scientific issue. Second, if social participation and democratization of science is a goal, then more emphasis should be placed on how students can realistically and confidently apply their learning to change social policy. In order to achieve this, education programs need to focus on legitimate real-life processes such as the PSB for engagement. PMID- 26557791 TI - Pencil-and-Paper Neural Networks: An Undergraduate Laboratory Exercise in Computational Neuroscience. AB - Although it has been more than 70 years since McCulloch and Pitts published their seminal work on artificial neural networks, such models remain primarily in the domain of computer science departments in undergraduate education. This is unfortunate, as simple network models offer undergraduate students a much-needed bridge between cellular neurobiology and processes governing thought and behavior. Here, we present a very simple laboratory exercise in which students constructed, trained and tested artificial neural networks by hand on paper. They explored a variety of concepts, including pattern recognition, pattern completion, noise elimination and stimulus ambiguity. Learning gains were evident in changes in the use of language when writing about information processing in the brain. PMID- 26557792 TI - Developing the Next Generation of Civic-Minded Neuroscience Scholars: Incorporating Service Learning and Advocacy Throughout a Neuroscience Program. AB - The Neuroscience Program of Moravian College aspires to produce well-informed, morally responsible and civically engaged individuals who will become the next generation of community leaders. Through the integration of service learning and advocacy into a Neuroscience curriculum, undergraduates are consistently involved in meaningful community service with instruction and reflection that enriches their learning experience, teaches civic responsibility and strengthens their college and local communities. As a result of our brain awareness outreach programming, formation of a local Society for Neuroscience chapter and advocacy for scientific funding initiatives, we have created a model of student engagement that has connected the academic to the practical in life altering ways for our undergraduates. Our service experiences have become an educational awakening as critical reflective thought creates new meaning and leads to growth and the ability to take informed actions. As expressed in our students' portfolio writings, our service learning endeavors have lead to personal growth, contributed to humane conditions and engaged these citizens in purposeful association with one another. PMID- 26557794 TI - Non-Fiction Memoirs in the Neuroscience Classroom: A Window into the Minds of Those Affected by Addiction. AB - When I first developed an Addiction course for the Honors College at UMass-Boston in 2006, it focused exclusively on the acute and long-term effects of psychoactive substances on the brain. However, I soon realized that a strictly biological perspective failed to capture how this complex disorder affected the whole person. Students had no insight into addicts' thoughts, feelings, behaviors or how their addiction affected others. To remedy this, students read two non fiction memoirs: Tweak (Nic Sheff, young adult addict) and Beautiful Boy (David Sheff, Nic's father) along with learning underlying neurobiology and pharmacology. Reading memoirs students saw firsthand the impact of addiction on individuals. Inspired by the diary structure of Tweak, one assignment asked students to collect data about themselves in order to determine their daily patterns/rituals and to contemplate the impact of removing these activities - like the addict after rehabilitation. Other assignments asked students to do close reading by selecting passages from Tweak and explaining how they related to different facets of addiction (biological, environmental, effect on individual), and to perform a comparative analysis between Beautiful Boy and Tweak to find points of intersection and divergence. Most recently, students used the text of Tweak to create interactive performances for a visiting high school class. Memoirs provided students with detailed, honest accounts of lives affected by addiction. The assignments and class discussions facilitated students understanding of the impact of addiction on individuals and their families, which was a powerful adjunct to learning about its underlying neurobiology and pharmacology. PMID- 26557793 TI - Extracellular Recording of Light Responses from Optic Nerve Fibers and the Caudal Photoreceptor in the Crayfish. AB - Few laboratory exercises have been developed using the crayfish as a model for teaching how neural processing is done by sensory organs that detect light stimuli. This article describes the dissection procedures and methods for conducting extracellular recording from light responses of both the optic nerve fibers found in the animal's eyestalk and from the caudal photoreceptor located in the ventral nerve cord. Instruction for ADInstruments' data acquisition system is also featured for the data collection and analysis of responses. The comparison provides students a unique view on how spike activities measured from neurons code image-forming and non-image-forming processes. Results from the exercise show longer latency and lower frequency of firing by the caudal photoreceptor compared to optic nerve fibers to demonstrate evidence of different functions. After students learn the dissection, recording procedure, and the functional anatomy, they can develop their own experiments to learn more about the photoreceptive mechanisms and the sensory integration of modalities by these light-responsive interneurons. PMID- 26557796 TI - Undergraduate Biocuration: Developing Tomorrow's Researchers While Mining Today's Data. AB - Biocuration is a time-intensive process that involves extraction, transcription, and organization of biological or clinical data from disjointed data sets into a user-friendly database. Curated data is subsequently used primarily for text mining or informatics analysis (bioinformatics, neuroinformatics, health informatics, etc.) and secondarily as a researcher resource. Biocuration is traditionally considered a Ph.D. level task, but a massive shortage of curators to consolidate the ever-mounting biomedical "big data" opens the possibility of utilizing biocuration as a means to mine today's data while teaching students skill sets they can utilize in any career. By developing a biocuration assembly line of simplified and compartmentalized tasks, we have enabled biocuration to be effectively performed by a hierarchy of undergraduate students. We summarize the necessary physical resources, process for establishing a data path, biocuration workflow, and undergraduate hierarchy of curation, technical, information technology (IT), quality control and managerial positions. We detail the undergraduate application and training processes and give detailed job descriptions for each position on the assembly line. We present case studies of neuropathology curation performed entirely by undergraduates, namely the construction of experimental databases of Amyotrophic Lateral Sclerosis (ALS) transgenic mouse models and clinical data from ALS patient records. Our results reveal undergraduate biocuration is scalable for a group of 8-50+ with relatively minimal required resources. Moreover, with average accuracy rates greater than 98.8%, undergraduate biocurators are equivalently accurate to their professional counterparts. Initial training to be completely proficient at the entry-level takes about five weeks with a minimal student time commitment of four hours/week. PMID- 26557795 TI - Using Tinbergen's Four Questions as the Framework for a Neuroscience Capstone Course. AB - Capstone courses for upper-division students are a common feature of the undergraduate neuroscience curriculum. Here is described a method for adapting Nikolaas Tinbergen's four questions to use as a framework for a neuroscience capstone course, in this case with a particular emphasis on neurotoxins. This course is intended to be a challenging opportunity for students to integrate and apply knowledge and skills gained from their major study, a B.S. in Biological Sciences with a Concentration in Integrative Physiology and Neurobiology. In particular, a broad, integrative approach is favored, with emphasis placed on primary literature, scientific process and effective, professional communication. To achieve this, Tinbergen's four questions were adapted and implemented as the overarching framework of the course. Tinbergen's questions range from the proximate to ultimate/evolutionary view, providing an excellent base upon which to teach students an integrative approach to understanding neuroscientific phenomena. For example, a particular neurotoxin can be examined from the proximate level (i.e., mechanism: how does this toxin specifically impact neural physiology) to the ultimate/evolutionary level (i.e., adaptation: why and to what extent did this toxin evolve naturally or the reason that it was initially invented by humans). The mechanics, goals, and objectives of the course are presented as we believe that it will serve as a flexible and useful model for neuroscience capstone courses concerning a wide variety of topics across multiple types of institutions. PMID- 26557797 TI - The Cognitive Neuroscience of Sign Language: Engaging Undergraduate Students' Critical Thinking Skills Using the Primary Literature. AB - This article presents a modular activity on the neurobiology of sign language that engages undergraduate students in reading and analyzing the primary functional magnetic resonance imaging (fMRI) literature. Drawing on a seed empirical article and subsequently published critique and rebuttal, students are introduced to a scientific debate concerning the functional significance of right hemisphere recruitment observed in some fMRI studies of sign language processing. The activity requires minimal background knowledge and is not designed to provide students with a specific conclusion regarding the debate. Instead, the activity and set of articles allow students to consider key issues in experimental design and analysis of the primary literature, including critical thinking regarding the cognitive subtractions used in blocked-design fMRI studies, as well as possible confounds in comparing results across different experimental tasks. By presenting articles representing different perspectives, each cogently argued by leading scientists, the readings and activity also model the type of debate and dialogue critical to science, but often invisible to undergraduate science students. Student self-report data indicate that undergraduates find the readings interesting and that the activity enhances their ability to read and interpret primary fMRI articles, including evaluating research design and considering alternate explanations of study results. As a stand-alone activity completed primarily in one 60-minute class block, the activity can be easily incorporated into existing courses, providing students with an introduction both to the analysis of empirical fMRI articles and to the role of debate and critique in the field of neuroscience. PMID- 26557798 TI - A Series of Computational Neuroscience Labs Increases Comfort with MATLAB. AB - Computational simulations allow for a low-cost, reliable means to demonstrate complex and often times inaccessible concepts to undergraduates. However, students without prior computer programming training may find working with code based simulations to be intimidating and distracting. A series of computational neuroscience labs involving the Hodgkin-Huxley equations, an Integrate-and-Fire model, and a Hopfield Memory network were used in an undergraduate neuroscience laboratory component of an introductory level course. Using short focused surveys before and after each lab, student comfort levels were shown to increase drastically from a majority of students being uncomfortable or with neutral feelings about working in the MATLAB environment to a vast majority of students being comfortable working in the environment. Though change was reported within each lab, a series of labs was necessary in order to establish a lasting high level of comfort. Comfort working with code is important as a first step in acquiring computational skills that are required to address many questions within neuroscience. PMID- 26557799 TI - Snack Cake 'Dissection': A Flipped Classroom Exercise to Engage Undergraduates With Basic Neuroanatomy. AB - This report describes a brief classroom activity for introducing basic neuroanatomical terminology and concepts to undergraduates in a survey-level course. Prior to completing the activity, students watched a short online lecture discussing the relevant material. During class, students worked in groups to 'dissect' snack cakes using the information they learned in the video and then reported and shared their 'results' using anatomical terminology. Quantitative feedback suggests that students found that the exercise was useful practice, that it helped increase their confidence in their ability to learn neuroanatomy, and that it helped increase their interest in the material generally. Data from an online anatomy quiz further supports the exercise's efficacy. Overall, the data suggest that this exercise may be a worthwhile addition to courses that introduce neuroanatomy to undergraduates. PMID- 26557800 TI - Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates. AB - The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 um, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization. PMID- 26557801 TI - When All the Giants Are Gone. PMID- 26557802 TI - Ishi no ue ni mo san nen(*) : Warming to the Changing Face of Neuroscience and Neuroscience Education. PMID- 26557804 TI - Ferrocene-Based Bioactive Bimetallic Thiourea Complexes: Synthesis and Spectroscopic Studies. AB - Bioactive 1,1'-(4,4'-di-ferrocenyl)di-phenyl thiourea and various metal complexes of this ligand have been successfully synthesized and characterized by using physicoanalytical techniques such as FT-IR and multinuclear ((1)H and (13)C) NMR spectroscopy along with melting point and elemental analyses. The interaction of the synthesized compounds with DNA has been investigated by using cyclic voltammetric and viscometric measurements. The intercalation of the complexes into the double helix structure of DNA is presumably occurring. Viscosity measurements of the complexes have shown that there is a change in length and this is regarded as the least ambiguous and the most critical test of the binding model in solution. The relative potential of the complexes as anti-bacterial, antifungal, and inhibition agents against the enzyme, alkaline phosphatase EC 3.1.3.1, has also been assessed and the complexes were found to be active inhibitors. PMID- 26557803 TI - An Instructor's Guide to (Some of) the Most Amazing Papers in Neuroscience. AB - Although textbooks are still assigned in many undergraduate science courses, it is now not uncommon, even in some of the earliest courses in the curriculum, to supplement texts with primary source readings from the scientific literature. Not only does reading these articles help students develop an understanding of specific course content, it also helps foster an ability to engage with the discipline the way its practitioners do. One challenge with this approach, however, is that it can be difficult for instructors to select appropriate readings on topics outside of their areas of expertise as would be required in a survey course, for example. Here we present a subset of the papers that were offered in response to a request for the "most amazing papers in neuroscience" that appeared on the listserv of the Faculty for Undergraduate Neuroscience (FUN). Each contributor was subsequently asked to describe briefly the content of their recommended papers, their pedagogical value, and the audiences for which these papers are best suited. Our goal is to provide readers with sufficient information to decide whether such articles might be useful in their own classes. It is not our intention that any article within this collection will provide the final word on an area of investigation, nor that this collection will provide the final word for the discipline as a whole. Rather, this article is a collection of papers that have proven themselves valuable in the hands of these particular educators. Indeed, it is our hope that this collection represents the inaugural offering of what will become a regular feature in this journal, so that we can continue to benefit from the diverse expertise of the FUN community. PMID- 26557805 TI - Mechanisms of Cross-protection by Influenza Virus M2-based Vaccines. AB - Current influenza virus vaccines are based on strain-specific surface glycoprotein hemagglutinin (HA) antigens and effective only when the predicted vaccine strains and circulating viruses are well-matched. The current strategy of influenza vaccination does not prevent the pandemic outbreaks and protection efficacy is reduced or ineffective if mutant strains emerge. It is of high priority to develop effective vaccines and vaccination strategies conferring a broad range of cross protection. The extracellular domain of M2 (M2e) is highly conserved among human influenza A viruses and has been utilized to develop new vaccines inducing cross protection against different subtypes of influenza A virus. However, immune mechanisms of cross protection by M2e-based vaccines still remain to be fully elucidated. Here, we review immune correlates and mechanisms conferring cross protection by M2e-based vaccines. Molecular and cellular immune components that are known to be involved in M2 immune-mediated protection include antibodies, B cells, T cells, alveolar macrophages, Fc receptors, complements, and natural killer cells. Better understanding of protective mechanisms by immune responses induced by M2e vaccination will help facilitate development of broadly cross protective vaccines against influenza A virus. PMID- 26557806 TI - Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60. AB - Minor histocompatibility antigens are MHC-bound peptides and contribute to the generation of allo-responses after allogeneic transplantation. H60 is a dominant minor H antigen that induces a strong CD8 T-cell response in MHC-matched allogeneic transplantation settings. Here, we report establishment of a TCR transgenic mouse line named J15, wherein T cells express TCRs specific for H60 in complex with H-2K(b), and different fates of the thymocytes expressing J15 TCRs in various thymic antigenic environments. Thymocytes expressing the J15 TCRs were positively selected and differentiated into CD8(+) single positive (SP) cells in the thymus of C57BL/6 mice, wherein the cognate antigen H60 is not expressed. However, thymocytes were negatively selected in thymus tissue where H60 was transgenically expressed under the control of the actin promoter, with double positive stages of cells being deleted. Despite the ability of the H60H peptide (LTFHYRNL) variant to induce cytotoxic activity from H60-specific CTL lines at ~50% of the activity induced by normal H60 peptides (LTFNYRNL), J15-expressing thymocytes were positively selected in the thymus where the variant H60H was transgenically expressed. These results demonstrate that a single amino-acid change in the H60 epitope peptide influences the fate of thymocytes expressing the cognate TCR. PMID- 26557807 TI - A New Triggering Receptor Expressed on Myeloid Cells (TREM) Family Member, TLT-6, is Involved in Activation and Proliferation of Macrophages. AB - The triggering receptor expressed on myeloid cells (TREM) family, which is abundantly expressed in myeloid lineage cells, plays a pivotal role in innate and adaptive immune response. In this study, we aimed to identify a novel receptor expressed on hematopoietic stem cells (HSCs) by using in silico bioinformatics and to characterize the identified receptor. We thus found the TREM-like transcript (TLT)-6, a new member of TREM family. TLT-6 has a single immunoglobulin domain in the extracellular region and a long cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motif-like domains. TLT-6 transcript was expressed in HSCs, monocytes and macrophages. TLT-6 protein was up regulated on the surface of bone marrow-derived and peritoneal macrophages by lipopolysaccharide stimulation. TLT-6 exerted anti-proliferative effects in macrophages. Our results demonstrate that TLT-6 may regulate the activation and proliferation of macrophages. PMID- 26557808 TI - Galectin-9 is Involved in Immunosuppression Mediated by Human Bone Marrow-derived Clonal Mesenchymal Stem Cells. AB - Bone marrow-derived mesenchymal stem cells (MSCs) have immunomodulatory properties and can suppress exaggerated pro-inflammatory immune responses. Although the exact mechanisms remain unclear, a variety of soluble factors are known to contribute to MSC-mediated immunosuppression. However, functional redundancy in the immunosuppressive properties of MSCs indicates that other uncharacterized factors could be involved. Galectin-9, a member of the beta galactoside binding galectin family, has emerged as an important regulator of innate and adaptive immunity. We examined whether galectin-9 contributes to MSC mediated immunosuppression. Galectin-9 was strongly induced and secreted from human MSCs upon stimulation with pro-inflammatory cytokines. An in vitro immunosuppression assay using a knockdown approach revealed that galectin-9 deficient MSCs do not exert immunosuppressive activity. We also provided evidence that galectin-9 may contribute to MSC-mediated immunosuppression by binding to its receptor, TIM-3, expressed on activated lymphocytes, leading to apoptotic cell death of activated lymphocytes. Taken together, our findings demonstrate that galectin-9 is involved in MSC-mediated immunosuppression and represents a potential therapeutic factor for the treatment of inflammatory diseases. PMID- 26557809 TI - Altered Gut Microbiota Composition in Rag1-deficient Mice Contributes to Modulating Homeostasis of Hematopoietic Stem and Progenitor Cells. AB - Hematopoietic stem and progenitor cells (HSPCs) can produce all kind of blood lineage cells, and gut microbiota that consists of various species of microbe affects development and maturation of the host immune system including gut lymphoid cells and tissues. However, the effect of altered gut microbiota composition on homeostasis of HSPCs remains unclear. Here we show that compositional change of gut microbiota affects homeostasis of HSPCs using Rag1 ( /-) mice which represent lymphopenic condition. The number and proportions of HSPCs in Rag1 (-/-) mice are lower compared to those of wild types. However, the number and proportions of HSPCs in Rag1 (-/-) mice are restored as the level of wild types through alteration of gut microbiota diversity via transferring feces from wild types. Gut microbiota composition of Rag1 (-/-) mice treated with feces from wild types shows larger proportions of family Prevotellaceae and Helicobacterceae whereas lower proportions of family Lachnospiraceae compared to unmanipulated Rag1 (-/-) mice. In conclusion, gut microbiota composition of lymphopenic Rag1 (-/-) mice is different to that of wild type, which may lead to altered homeostasis of HSPCs. PMID- 26557811 TI - Standardization of Diagnostics in Blood Safety. PMID- 26557810 TI - Engagement of CD99 Reduces AP-1 Activity by Inducing BATF in the Human Multiple Myeloma Cell Line RPMI8226. AB - CD99 signaling is crucial to a diverse range of biological functions including survival and proliferation. CD99 engagement is reported to augment activator protein-1 (AP-1) activity through mitogen-activated protein (MAP) kinase pathways in a T-lymphoblastic lymphoma cell line Jurkat and in breast cancer cell lines. In this study, we report that CD99 differentially regulated AP-1 activity in the human myeloma cell line RPMI8226. CD99 was highly expressed and the CD99 engagement led to activation of the MAP kinases, but suppressed AP-1 activity by inducing the expression of basic leucine zipper transcription factor, ATF-like (BATF), a negative regulator of AP-1 in RPMI8226 cells. By contrast, engagement of CD99 enhanced AP-1 activity and did not change the BATF expression in Jurkat cells. CD99 engagement reduced the proliferation of RPMI8226 cells and expression of cyclin 1 and 3. Overall, these results suggest novel CD99 functions in RPMI8226 cells. PMID- 26557812 TI - Standardization of NAT for Blood-Borne Pathogens. AB - Assays based on nucleic acid amplification technology (NAT) are increasingly used for screening of blood and for diagnosis or monitoring of patients. Both regulatory requirements for blood screening and international recommendations for the treatment of patients are based on common reference materials available globally for the standardization of NAT assays. World Health Organization International Standards (WHO ISs) and International Reference Panels (WHO IRPs) are primary reference materials. The characterization and manufacture of WHO reference materials as well as their evaluation is performed on behalf of the WHO by collaborating centers; their establishment is decided upon by the WHO Expert Committee on Biological Standardization (ECBS). The potency of the first WHO IS is defined by the 'international unit' (IU) which should be maintained upon replacement of the IS. The IU, unlike copy number or genome equivalent, is defined by the IS with a physical existence, is available worldwide, and allows traceability and comparability of results. The anticipated use of WHO ISs is the calibration of secondary standards or the validation of essential assay features, e.g. limit of detection. PMID- 26557813 TI - Bench Test for the Detection of Bacterial Contamination in Platelet Concentrates Using Rapid and Cultural Detection Methods with a Standardized Proficiency Panel. AB - BACKGROUND: The most frequent infectious complication in transfusion therapy in developed countries is related to the bacterial contamination of platelet concentrates (PCs). Rapid and cultural screening methods for bacterial detection in platelets are available, but external performance evaluation, especially of rapid methods, has been difficult to realize so far. Here we summarize the results of three individual collaborative trials using an external quality assessment program (EQAP) for the application of current rapid and cultural screening methods. METHODS: Three different modules were available for the detection of bacterial contamination: module 1: rapid methods, module 2: culture methods, module 3: bacterial identification methods. The sample set-up included up to six different bacterial strains, 1-2 negative samples and 4-6 positive samples with stabilized bacterial cell counts (approximately 10(3)/10(4)/10(5) CFU/ml). Time schedule for testing was limited (module 1: 6 h, module 2 and 3: 7 days). RESULTS: Samples of module 1 were analyzed with two different rapid methods (BactiFlow, NAT). The results of the three individual collaborative trials showed that all participants detected the negative samples with both assays correctly. Samples spiked with 10(4) to 10(5) CFU/ml of bacteria obtained positive results with both rapid screening methods, whereas samples spiked with only 10(3) CFU/ml disclosed a lower number of correctly identified positive results by NAT (86.6-93.8% sensitivity) compared to BactiFlow (100% sensitivity). The results for modules 2 and 3 revealed a 100% diagnostic sensitivity and specificity in all three collaborative trials. CONCLUSION: This proficiency panel facilitates the verification of the analytical sensitivity of rapid and cultural bacterial detection systems under controlled routine conditions. The concept of samples provided in this EQAP has three main advantages: i) samples can be examined by both rapid and culture methods, ii) the provided material is matrix equivalent, and iii) the sample material is ready-to-use. PMID- 26557814 TI - Retrospective Review of Platelet Transfusion Practices during 2013 Dengue Epidemic of Delhi, India. AB - BACKGROUND: Dengue infection is a major public health problem. During explosive outbreaks, there is sudden surge in demands of platelet products. The present study was carried out in order to review platelet transfusion practices during the epidemic of dengue. METHODS: We retrospectively reviewed the clinical details including the platelet counts and haemorrhagic tendencies of dengue patients as well as the transfusion requirements of diagnosed dengue cases admitted at our centre. RESULTS: A total of 1,750 random donor platelet and 114 single donor platelet units were transfused to 531 patients. 23.2% platelet transfusions were found to be inappropriate Mean dosage of platelets transfused was 2 * 10(11) platelets per patient. A total of 347 (65.3%) patients had bleeding diathesis at the time of presentation. Skin and the oropharynx were the most common bleeding sites. Major bleeding was seen in 119 (34.3%) patients, whereas 228 (65.7%) patients had minor bleeding episodes. CONCLUSION: The study emphasises the need for minimising unnecessary transfusions and for using this scarce resource judiciously, which can be achieved by strict adherence to evidence-based transfusion guidelines and regular review of the on-going transfusion practices. PMID- 26557815 TI - Characterization of Markers of the Progression of Human Parvovirus B19 Infection in Virus DNA-Positive Plasma Samples. AB - BACKGROUND: Accurate characterization of the infection stage in parvovirus B19(B19V)-positive plasma donations would help establish the donation deferral period to contribute to a safe fractionation pool of plasma. METHODS: Viral DNA load of 74 B19V DNA-positive plasma samples from whole blood donations was determined by titration using nucleic acid testing. Markers of cellular (neopterin) and humoral (B19V-specific IgM and IgG) immune response were determined by ELISA in 32 B19V DNA-positive samples and in 13 B19V DNA-negative samples. The infection progression profile was estimated according to B19V DNA load and the presence of immune response markers. RESULTS: B19V DNA load in the 74 samples was 10(6)-10(13) IU/ml. The distribution of 14 out of 32 selected B19V DNA-positive samples plus 2 B19V DNA-negative samples with no immune response marker followed along an upward curve according to B19V DNA load. After the peak, the distribution of 18 immune marker-positive samples followed along a downward curve according to their B19V DNA load and was grouped as follows: neopterin (n = 4), neopterin+ IgM (n = 8), neopterin + IgM + IgG (n = 3), IgM + IgG (n = 2), IgM (n = 1). There were 11 B19V DNA-negative IgG-positive samples. CONCLUSION: This study of B19V-DNA load and levels of neopterin, IgM, and IgG allows for reliable characterization and distribution into the different stages of B19V infection. PMID- 26557816 TI - Evaluation of Risk Minimisation Measures for Blood Components - Based on Reporting Rates of Transfusion-Transmitted Reactions (1997-2013). AB - BACKGROUND: To assess the impact of safety measures, we compared reporting rates of transfusion-related reactions before and after the implementation of six measures in 1999, 2004, 2006, 2008 and 2009. METHODS: Reporting rates of transfusion-transmitted bacterial infection (TTBI), viral infection (TTVI) and immune-mediated transfusion-related acute lung injury (TRALI) were calculated on the basis of confirmed annual reports and distributed blood components. RESULTS: The introduction of HCV NAT testing caused a significant reduction of HCV reporting rate from 1:0.6 to 1:83.16 million administered blood components (p < 0.0001), donor screening for antibodies to hepatitis B core antigen caused a reduction of HBV reporting rate from 1:2.90 to 1:10.70 million units (p = 0.0168). A significant reduction from 1:0.094 to 1:2.42 million fresh frozen plasma (FFP) units could also be achieved by risk minimisation TRALI measures (p < 0.0001). Implementation of pre-donation sampling did not result in a significant decrease in TTBI, whereas limitation of shelf life for platelet concentrate (PC) minimised the TTBI reporting rate from 1:0.088 to 1:0.19 million PC units (p = 0.041). For HIV NAT pool testing, no significant reduction in HIV transmission was found due to very low reporting rates (1:10 million versus 1:27 million blood components, p = 0.422). CONCLUSION: On the basis of haemovigilance data, a significant benefit could be demonstrated for four of six implemented safety measures. PMID- 26557818 TI - Retraction Statement. PMID- 26557819 TI - Targeted Therapies in Breast Cancer: New Approaches and Old Challenges. PMID- 26557817 TI - Hepatitis E Virus. PMID- 26557820 TI - Targeted Therapies in Triple-Negative Breast Cancer. AB - Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed. PMID- 26557821 TI - Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer. AB - Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the current review is on the intracellular PI3K/AKT/mTOR signalling pathway and cyclin-dependant kinases (CDKs) in oestrogen receptor (ER)-positive breast cancer. Study results clearly show that both inhibition of the PI3K/AKT/mTOR pathway and CDK4/6 are promising ways to improve the efficacy of endocrine treatment in ER-positive breast cancer patients with comparably few side effects. Further clinical trials are needed to identify the patient population who would benefit most from a dual inhibition. PMID- 26557822 TI - Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review. AB - About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview. PMID- 26557823 TI - Surgical Strategies in the Treatment of Gynecomastia Grade I-II: The Combination of Liposuction and Subcutaneous Mastectomy Provides Excellent Patient Outcome and Satisfaction. AB - BACKGROUND: Gynecomastia (GM) is a benign condition with glandular tissue enlargement of the male breast. GM is classified into 4 grades of increasing severity. We describe a series of GM grade I-II, diagnosed, treated surgically and analyzed regarding feasibility, complication rate, and satisfaction. METHODS: From 2005 to 2012, a chart review was performed for 53 patients. Preoperative examination included endocrine and urological examination and exclusion of other pathological conditions. The surgical technique consisted of liposuction through an inframammarian-fold incision and excision of the glandular tissue by a minimal periareolar approach. RESULTS: A total number of 53 male patients with 104 breasts were available for analysis. By liposuction, a median of 300 ml (range: 10-1000 ml) was aspirated from each breast and 25.1 g (range: 3-233 g) gland tissue was resected. Surgery lasted between 25 and 164 min per patient (median: 72 min). 2 postoperative hemorrhages occurred (n = 2, 3.8%). 2 patients underwent re-operation due to cosmetic reasons (n = 2, 3.8%). CONCLUSIONS: This analysis demonstrates that treatment of GM grade I-II can easily be performed by liposuction combined with subcutaneous resection of the glandular tissue as a minimally invasive and low-impact surgical treatment with a low rate of complications and excellent patient satisfaction. Preoperative workup is important to rule out specific diseases or malignancy causing the GM. PMID- 26557824 TI - AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2015. PMID- 26557825 TI - AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2015. PMID- 26557826 TI - Breast Lesions during Pregnancy - a Diagnostic Challenge: Case Report. AB - BACKGROUND: Palpable masses of the breast often occur during pregnancy and should be further investigated. The standard diagnostic during pregnancy is an ultrasound combined, if needed, with a core needle biopsy. Most lesions are benign in younger women but, nevertheless, the incidence of pregnancy-associated breast cancer is 1 in 3,000 deliveries and rising. CASE REPORT: We report the case of a 24-year-old patient diagnosed with a palpable breast lesion at 37 weeks of gestation. An ultrasound was performed and the lesion was rated BI-RADS 4. The initial core needle biopsy showed a ductal carcinoma in situ. After delivery and ablactating, a mammography, breast magnetic resonance imaging and a second ultrasound-guided biopsy was performed. Due to the inconclusive imaging and histological results, a wide excision was performed and a juvenile papillomatosis was confirmed. No further resection was necessary as the initial margins were sufficient. CONCLUSION: This case suggests that the diagnosis of masses of the breast during pregnancy and lactation can be quite difficult. Diagnosis should be confirmed by an excision biopsy and by histological examination through an experienced pathologist. As a significant proportion of papillomas contain malignant regions, an argument exists for the complete excision of all papillary tumours. PMID- 26557828 TI - Exome Sequencing of a Family with Bardet-Biedl Syndrome Identifies the Common Russian Mutation c.1967_1968delTAinsC in BBS7. AB - Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by obesity, postaxial polydactyly, retinitis pigmentosa, mental retardation, and kidney abnormalities. At least 19 genes have been shown to be associated with BBS, and therefore, genetic testing is highly complicated. We used an Illumina MiSeq platform for whole exome sequencing analysis of a family with strong clinical features of BBS. A homozygous c.1967_1968delTAinsC (p.Leu656fsX673; RefSeq NM_176824.2) mutation in BBS7 was identified in both affected children, while their healthy sibling and the non-consanguineous parents were heterozygous for this allele. Genotyping of 2,832 DNA samples obtained from Russian blood donors revealed 2 additional heterozygous subjects (0.07%) with the c.1967_1968delTAinsC mutation. These findings may facilitate the genetic diagnosis for Slavic BBS patients. PMID- 26557829 TI - Inflammatory Bowel Diseases: Current Medical and Surgical Therapy. PMID- 26557827 TI - 14th St. Gallen International Breast Cancer Conference 2015: Evidence, Controversies, Consensus - Primary Therapy of Early Breast Cancer: Opinions Expressed by German Experts. AB - The key topics of this year's 14th St. Gallen Consensus Conference on the diagnosis and therapy of primary breast cancer were again questions about breast surgery and axillary surgery, radio-oncology and systemic therapy options in consideration of tumor biology, and the clinical application of multigene assays. This year, the consensus conference took place in Vienna. From a German perspective, it makes sense to substantiate the results of the vote of the international panel representing 19 countries in light of the updated national therapy recommendations of the AGO (Arbeitsgemeinschaft Gynakologische Onkologie). Therefore, 14 German breast cancer experts, 3 of whom are members of the International St. Gallen Panel, have commented on the voting results of the St. Gallen Consensus Conference 2015 in relation to clinical routine in Germany. PMID- 26557830 TI - New Imaging Techniques in the Diagnosis of Inflammatory Bowel Diseases. AB - BACKGROUND: Cross-sectional imaging modalities are fundamental in the management of patients with inflammatory bowel disease (IBD) from the first diagnosis and throughout the entire course of the disease. Over the past few years, the use of magnetic resonance (MR) imaging (MRI) has considerably increased, and no other imaging modality has experienced as advanced a development as MRI. METHODS: A comprehensive literature search (PubMed/Medline) using keywords such as 'MR enterography', 'imaging modalities', 'IBD', and 'Crohn's disease' was performed. 48 articles published between 1999 and 2015 were systematically reviewed. In this article, besides the current standard MRI techniques, we review novel and implementable for routine use MR techniques. The use of positron emission tomography/computed tomography (PET/CT) and hybrid imaging such as PET/MRI with enormous potential will also be briefly discussed. RESULTS: New imaging techniques such as diffusion-weighted imaging, dynamic contrast-enhanced MR perfusion, and MR motility imaging yield advanced findings about changes in the microenvironment and alterations in motility of the affected bowel segment, and are proven to improve the diagnostic accuracy in assessing the scale, activity level, and severity of the IBD. Novel magnetization transfer imaging allows direct visualization of fibrosis in the bowel wall. CONCLUSION: Diffusion weighted imaging can be easily implemented in standard MRI for routine use to further enhance the diagnostic accuracy in disease assessment. For validation of magnetization transfer imaging, larger studies are warranted. PMID- 26557832 TI - Surgical Principles in the Treatment of Ulcerative Colitis. AB - BACKGROUND: The primary treatment of ulcerative colitis (UC) is conservative; surgical intervention is carried out in the case of therapy-refractory situation, imminent or malignant transformation, or complications. Surgery for UC should be indicated by interdisciplinary means. Despite the development of drug therapy - in particular the introduction of biologics -, a surgical intervention becomes necessary in a relevant proportion of patients with UC throughout lifetime. METHODS: A selective literature search was conducted, taking into account the current studies, reviews, meta-analyses, and guidelines. PubMed served as a database. The present work gives an overview of the surgical options, outcome as well as peri- and postoperative management for patients with UC. RESULTS: Approximately 20% of patients with UC will require surgery during the course of their disease. The rate of colectomy after a disease duration of 10 years is at approximately 16%. Unlike Crohn's disease, UC is principally surgically curable since it is naturally limited to the colon and rectum. Restorative proctocolectomy with an ileal pouch-anal anastomosis represents the surgical treatment of choice. Large studies show a postoperative complication rate of around 30% and a low mortality of 0.1% for this procedure. Chronic pouchitis is one of the main factors limiting the surgical success of curing UC. Despite a high postoperative complication rate, there is a long-term pouch success rate of >90% after 10 and 20 years of follow-up. CONCLUSION: A close cooperation between the various disciplines in the pre- and postoperative setting is essential for an optimal outcome of patients with UC. Despite a 30% rate of early postoperative complications, normal quality of life can ultimately be reached in more than 90% of patients in experienced centers. PMID- 26557831 TI - Medical Therapy of Active Ulcerative Colitis. AB - BACKGROUND: Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. METHODS: A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. RESULTS: In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. CONCLUSION: There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options. PMID- 26557833 TI - Occult and Manifest Colorectal Carcinoma in Ulcerative Colitis: How Does It Influence Surgical Decision Making? AB - BACKGROUND: The incidence of colorectal cancer (CRC) among patients with ulcerative colitis (UC) is increased compared to the general population. The diagnosis of CRC potentially influences surgical decision making in patients with UC. METHODS: This review considers clinical studies, systematic reviews, and guidelines on the surgical therapy of CRC in UC. We searched the bibliographic databases The Cochrane Library and Medline (applying MeSH terms such as 'Colitis, Ulcerative/surgery', 'Colorectal Neoplasms', and 'Proctocolectomy, Restorative') with no restriction on language, date, or country. Search results as well as references of relevant publications were independently screened by both authors of this review. RESULTS: The surgical gold standard for proven CRC in UC is oncological proctocolectomy, if possible preferably as a restorative procedure with formation of an ileal pouch-anal anastomosis. Mucosectomy and hand-sewn anastomosis is the preferred option for fashioning the anastomosis in these patients, especially in case of dysplasia or cancer in the rectum, although the available data is not conclusive. In highly selected cases of patients with histologically confirmed sporadic CRC without dysplasia in multiple random biopsies and without relevant inflammation, a conventional limited oncological resection is adequate. If UC patients with rectal cancer require radiotherapy, it should be performed in a neoadjuvant setting because of the high risk of radiation-induced pouch failure. CONCLUSION: Although restorative proctocolectomy is clearly the gold standard therapy for patients with CRC in UC, surgical decision making has to take into account the various settings and patient factors. PMID- 26557834 TI - Medical Therapy of Fibrostenotic Crohn's Disease. AB - INTRODUCTION: The present review serves to provide a concise overview of the current knowledge on therapeutic strategies with regard to fibrostenotic lesions in Crohn's disease. METHODS: A literature search was performed focusing on the last 5 years, and current concepts of pathophysiology, epidemiology, and treatment have been summarized. RESULTS: Fibrostenotic lesions in Crohn's disease are currently considered to be a consequence of the chronic inflammatory nature of the disease. Hence, therapeutic strategies are limited to the concept that early treatment of the inflammatory lesions can prevent structural changes, and to various endoscopic and surgical approaches. Direct targeting of the fibrostenotic lesion itself has not been the focus until now. This review will provide an overview of the pathophysiology and epidemiology of fibrostenotic lesions including current therapeutic approaches. Since research with regard to other organ systems and fibrosis is far more advanced, current strategies from available studies in these areas will be discussed. The results and the potential impact for Crohn's disease will be considered. CONCLUSION: The vision of these approaches is to reverse structural changes and restore normal function. PMID- 26557835 TI - Medical Therapy of Perianal Crohn's Disease. AB - BACKGROUND: Development of perianal fistulas are a common feature of Crohn's disease (CD). Consequences are severe impairment of quality of life as well as potentially life-threatening complications like abscess formation or bacterial sepsis. Therefore, appropriate treatment is an important task in the management of CD. METHODS: This review describes the epidemiology, pathogenesis, diagnosis, and conservative medical treatment of perianal CD with regard to the available literature. In February 2015, a PubMed search was performed with the following terms (combined and separate): 'Crohn's disease management', 'Crohn's disease complications', 'perianal Crohn's disease', 'fistulizing Crohn's disease', 'perianal fistulas', 'fistula healing', 'fistula closure'. From the search results, 36 articles were chosen as core elements of this review. RESULTS: Pelvic magnetic resonance imaging and rectal endosonography are established diagnostic approaches to evaluate perianal fistulas in conjunction with endoscopy. Antibiotics, thiopurines, and calcineurin inhibitors are useful agents in the management of perianal CD. The availability of anti-TNF-alpha therapies has substantially changed the prospects and goals of medical treatment, and fistula healing seems to be possible in a substantial proportion of patients. CONCLUSION: Antibiotics and several immunosuppressive drugs have improved the treatment of fistulizing CD and should be combined with surgical measures. PMID- 26557836 TI - Indications and Specific Surgical Techniques in Crohn's Disease. AB - BACKGROUND: Crohn's disease (CD) as one of the major entities of chronic inflammatory bowel diseases can affect all segments of the gastrointestinal tract but occurs most often in the small bowel, the terminal ileum, the colon, and the rectum. Typical symptoms include tiredness, lower abdominal pain, fever, and diarrhea, which are initially treated by conservative measures. Most patients will eventually develop complications such as fistulas, abscesses, or strictures. Surgery is often unavoidable in these cases. METHODS: This review considers studies on the treatment of CD, published from 1979 up to now. The literature regarding the course, complications, and surgical therapy of CD was reviewed. Searches were performed in PubMed, using the following key words: CD, surgery, immunosuppression, guidelines, malnutrition as well as appropriate sub-items. In most cases the literature is limited to detailed information on specific therapeutic or diagnostic topics. Moreover, many studies are designed retrospectively and with a small number of patients. Additionally, our long standing experience with patients suffering from CD is taken into consideration in this review. RESULTS: There is a wide variety of indications for surgery in CD which includes complications like strictures, fistulas and abscess formation, neoplasia, or refractoriness to medical therapy. The risk of developing complications is about 33% after 5 years, and 50% after 20 years. Furthermore, one-third of CD patients need surgical therapy within the first 5 years of diagnosis. The treatment requires close cooperation between gastroenterologists and surgeons. When indicated, surgery should be performed in a 'conservative' fashion, i.e. as limited as possible, in order to achieve the required result and to avoid small bowel syndrome. CONCLUSION: This article provides a complete overview of indications and specific surgical treatment in patients with CD. Surgery is typically indicated when complications of CD occur. An interdisciplinary collaboration is necessary in order to ensure optimal indications and timing of surgery. This is of paramount importance to achieve the ultimate goal, i.e. a good quality of life of the patients. PMID- 26557838 TI - Inflammatory Bowel Diseases: Current Medical and Surgical Therapy. PMID- 26557837 TI - Endoscopic Therapy in Inflammatory Bowel Diseases. AB - BACKGROUND: Endoscopy is an essential diagnostic and therapeutic modality in the clinical care of inflammatory bowel disease (IBD) patients. Endoscopic therapy can be used for treatment of disease-related strictures, surveillance and resection of intraepithelial neoplasia, and treatment of fistulas or disease related complications, and is currently being evaluated regarding its capacity in in vivo molecular imaging procedures. METHODS: A literature search using Medline and Science Citation Index was performed in March 2015. All studies on endoscopic therapy in IBD published from 1980 to 2015 (March) were reviewed. Potential studies were initially screened by title and abstract. The terms 'endoscopy IBD', 'endoscopy therapy IBD', 'dilatation IBD', 'strictureplasty Crohn's disease', 'endoscopy therapy fistula', 'endoscopy toxic megacolon', 'endoscopy dysplasia IBD', 'endoscopy complications IBD', and 'molecular imaging IBD' were used in the search. A total of 115 articles were studied to construct this review. RESULTS: Dilatation is most useful in short anastomotic strictures, but can be also undertaken in colonic strictures. Strictures in ulcerative colitis are always suspicious for neoplasia and should be evaluated carefully. Lesions with intraepithelial neoplasia can be resected when complete removal can be assured. The finding of carcinoma or high-grade dysplasia in a random biopsy is an indication for colectomy. If intraepithelial neoplasia is present in random biopsy specimens, colectomy should similarly be recommended. Endoscopic therapy of Crohn's fistulas is a possible emerging technology. In vivo molecular imaging is currently being studied in IBD patients and offers promising therapeutic opportunities. CONCLUSION: Therapeutic endoscopy is indispensable in the management of IBD. It has to be carefully evaluated against alternative surgical options but often offers an effective therapeutic approach. (c) 2015 S. Karger GmbH, Freiburg. PMID- 26557839 TI - The New Era of Interferon-Free Treatment of Chronic Hepatitis C. AB - BACKGROUND: Within the development and approval of several new direct-acting antivirals (DAA) against hepatitis C virus (HCV), a new era of hepatitis C therapy has begun. Even more treatment options are likely to become available during the next 1-2 years. METHODS: A summary of the current phase II and III trials investigating DAA and a review of the recent HCV guidelines was conducted. RESULTS: With the development of new potent DAA and the approval of different DAA combinations, cure rates of HCV infection of >90% are achievable for almost all HCV genotypes and stages of liver disease. Currently available DAA target different steps in the HCV replication cycle, in particular the NS3/4A protease, the NS5B polymerase, and the NS5A replication complex. Treatment duration varies between 8 and 24 weeks depending on the stage of fibrosis, prior treatment, HCV viral load, and HCV genotype. Ribavirin is required only for some treatment regimens and may be particularly beneficial in patients with cirrhosis. DAA resistance influences treatment outcome only marginally; thus, drug resistance testing is not routinely recommended before treatment. In the case of treatment failure, however, resistance testing should be performed before re-treatment with other DAA is initiated. CONCLUSION: With the new, almost side effect-free DAA treatment options chronic HCV infection became a curable disease. The clinical benefit of DAA combination therapies in patients with advanced cirrhosis and the effects on incidence rates of hepatocellular carcinoma remain to be determined. PMID- 26557840 TI - Conjunctival Microangiopathy in a Patient with Neovascular Glaucoma. AB - PURPOSE: To report a case of conjunctival microangiopathy secondary to diabetes presenting as a red eye 5 years after glaucoma implant surgery for neovascular glaucoma. MATERIALS AND METHODS: A 52-year-old Tongan male with a past history of neovascular glaucoma secondary to proliferative diabetic retinopathy underwent slitlamp examination and color photography of the anterior and posterior segment, in addition to anterior segment fluorescein angiography. RESULTS: The conjunctival venules perilimbally demonstrated tortuosity and dilation (saccular, fusiform and tricornuate). Capillaries were tortuous, with sparse microaneurysm formation, and arterioles were attenuated. Anterior segment fluorescein angiography showed generalized iris ischemia, extensive perilimbal microvascular degenerative changes and leakage of fluorescein into the anterior chamber. We are unaware of previous reports in the literature on conjunctival microangiopathy secondary to diabetes presenting as a red eye. CONCLUSIONS: We hypothesized that the clinical features in our case may have been modified by a combination of postoperative wound healing and degenerative vascular remodeling, in addition to microvascular alterations secondary to both diabetes and consequent ocular ischemia, which may have played a role. PMID- 26557841 TI - Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy. AB - BACKGROUND: The following calcium (Ca) correction formula (Payne) is conventionally used for serum Ca estimation: corrected total Ca (TCa) (mg/dl) = TCa (mg/dl) + [4 - albumin (g/dl)]; however, it is inapplicable to advanced chronic kidney disease (CKD) patients. METHODS: 1,922 samples in CKD G4 + G5 patients and 341 samples in CKD G5D patients were collected. Levels of TCa (mg/day), ionized Ca(2+) (iCa(2+)) (mmol/l) and other clinical parameters were measured. We assumed the corrected TCa to be equal to eight times the iCa(2+) value (measured corrected TCa). We subsequently performed stepwise multiple linear regression analysis using the clinical parameters. RESULTS: The following formula was devised from multiple linear regression analysis. For CKD G4 + G5 patients: approximated corrected TCa (mg/dl) = TCa + 0.25 * (4 - albumin) + 4 * (7.4 - pH) + 0.1 * (6 - P) + 0.22. For CKD G5D patients: approximated corrected TCa (mg/dl) = TCa + 0.25 * (4 - albumin) + 0.1 * (6 - P) + 0.05 * (24 - HCO3 (-)) + 0.35. Receiver operating characteristic analysis showed the high values of the area under the curve of approximated corrected TCa for the detection of measured corrected TCa >=8.4 mg/dl and <=10.4 mg/dl for each CKD sample. Both intraclass correlation coefficients for each CKD sample demonstrated superior agreement using the new formula compared to the previously reported formulas. CONCLUSION: Compared to other formulas, the approximated corrected TCa values calculated from the new formula for patients with CKD G4 + G5 and CKD G5D demonstrates superior agreement with the measured corrected TCa. PMID- 26557842 TI - Thrice-Weekly Nocturnal In-Centre Haemodiafiltration: A 2-Year Experience. AB - BACKGROUND: Adequate control of plasma phosphate without phosphate binders is difficult to achieve on a thrice-weekly haemodialysis schedule. The use of quotidian nocturnal dialysis is effective but not practical in the in-centre setting. This quality improvement project was set up as an exercise allowing the evaluation of small-solute clearance by combining convection with extended-hour dialysis in a thrice-weekly hospital setting. METHODS: A single-centred, prospective analysis of patients' electronic records was performed from August 2012 to July 2014. The duration of haemodiafiltration was increased from a median of 4.5 to 8 h. Dialysis adequacy, biochemical parameters and medications were reviewed on a monthly basis. A reduction in plasma phosphate was anticipated, so all phosphate binders were stopped. RESULTS: Since inception, 14 patients have participated with over 2,000 sessions of dialysis. The pre-dialysis phosphate level fell from a mean of 1.52 +/- 0.4 to 1.06 +/- 0.1 mmol/l (p < 0.05). The average binder intake of 3.26 +/- 2.6 tablets was eliminated. A normal plasma phosphate range has been maintained with increased dietary phosphate intake and no requirement for intradialytic phosphate supplementation. CONCLUSION: Phosphate control can be achieved without the need for binders or supplementation on a thrice-weekly in-centre haemodiafiltration program. PMID- 26557844 TI - Lung Segmentation in 4D CT Volumes Based on Robust Active Shape Model Matching. AB - Dynamic and longitudinal lung CT imaging produce 4D lung image data sets, enabling applications like radiation treatment planning or assessment of response to treatment of lung diseases. In this paper, we present a 4D lung segmentation method that mutually utilizes all individual CT volumes to derive segmentations for each CT data set. Our approach is based on a 3D robust active shape model and extends it to fully utilize 4D lung image data sets. This yields an initial segmentation for the 4D volume, which is then refined by using a 4D optimal surface finding algorithm. The approach was evaluated on a diverse set of 152 CT scans of normal and diseased lungs, consisting of total lung capacity and functional residual capacity scan pairs. In addition, a comparison to a 3D segmentation method and a registration based 4D lung segmentation approach was performed. The proposed 4D method obtained an average Dice coefficient of 0.9773 +/- 0.0254, which was statistically significantly better (p value ?0.001) than the 3D method (0.9659 +/- 0.0517). Compared to the registration based 4D method, our method obtained better or similar performance, but was 58.6% faster. Also, the method can be easily expanded to process 4D CT data sets consisting of several volumes. PMID- 26557845 TI - Statistical Analysis of Haralick Texture Features to Discriminate Lung Abnormalities. AB - The Haralick texture features are a well-known mathematical method to detect the lung abnormalities and give the opportunity to the physician to localize the abnormality tissue type, either lung tumor or pulmonary edema. In this paper, statistical evaluation of the different features will represent the reported performance of the proposed method. Thirty-seven patients CT datasets with either lung tumor or pulmonary edema were included in this study. The CT images are first preprocessed for noise reduction and image enhancement, followed by segmentation techniques to segment the lungs, and finally Haralick texture features to detect the type of the abnormality within the lungs. In spite of the presence of low contrast and high noise in images, the proposed algorithms introduce promising results in detecting the abnormality of lungs in most of the patients in comparison with the normal and suggest that some of the features are significantly recommended than others. PMID- 26557843 TI - A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome. AB - BACKGROUND/AIMS: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. METHODS: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. RESULTS: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. CONCLUSIONS: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome. PMID- 26557846 TI - CyberPsychological Computation on Social Community of Ubiquitous Learning. AB - Under the modern network environment, ubiquitous learning has been a popular way for people to study knowledge, exchange ideas, and share skills in the cyberspace. Existing research findings indicate that the learners' initiative and community cohesion play vital roles in the social communities of ubiquitous learning, and therefore how to stimulate the learners' interest and participation willingness so as to improve their enjoyable experiences in the learning process should be the primary consideration on this issue. This paper aims to explore an effective method to monitor the learners' psychological reactions based on their behavioral features in cyberspace and therefore provide useful references for adjusting the strategies in the learning process. In doing so, this paper firstly analyzes the psychological assessment of the learners' situations as well as their typical behavioral patterns and then discusses the relationship between the learners' psychological reactions and their observable features in cyberspace. Finally, this paper puts forward a CyberPsychological computation method to estimate the learners' psychological states online. Considering the diversity of learners' habitual behaviors in the reactions to their psychological changes, a BP-GA neural network is proposed for the computation based on their personalized behavioral patterns. PMID- 26557848 TI - Willingness to Adopt Telemedicine in Major Iraqi Hospitals: A Pilot Study. AB - The Iraqi healthcare services are struggling to regain their lost momentum. Many physicians and nurses left Iraq because of the current situation in the country. Despite plans of calling back the skilled health workforce, they are still worried by the disadvantages of their return. Hence, technology plays a central role in taking advantage of their profession through the use of telemedicine. Studying the factors that affect the implementation of telemedicine is necessary. Telemedicine covers network services, policy makers, and patient understanding. A framework that includes the influencing factors in adopting telemedicine in Iraq was developed in this study. A questionnaire was distributed among physicians in Baghdad Medical City to examine the hypothesis on each factor. The Statistical Package for the Social Sciences was utilized to verify the reliability of the questionnaire and Cronbach's alpha test shows that the factors have values more than 0.7, which are standard. PMID- 26557847 TI - Molecular Features and Methylation Status in Early Onset (<=40 Years) Colorectal Cancer: A Population Based, Case-Control Study. AB - Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients <=40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%). KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p = 0.02). Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis. PMID- 26557849 TI - Seroprevalence of Herpes Simplex Virus Infection in HIV Coinfected Individuals in Eastern India with Risk Factor Analysis. AB - Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes while HSV 1 is responsible for orolabial and facial lesions. In immunocompromised individuals, like HIV patients, impaired immunity leads to more frequent symptomatic and asymptomatic HSV infection. Fifty-two blood samples from HIV patients with clinically diagnosed HSV infection were taken as cases, while 45 blood samples each from HIV-infected (HIV control) and noninfected patients without any herpetic lesion (non-HIV control) were taken as control. Serum was tested for IgM and IgG antibodies of both HSV-1 and HSV-2 by ELISA. The seroprevalence was compared among the three groups of study population, considering the demographic and socioeconomic parameters. The HSV-2 IgM was significantly higher (p < 0.005) in the HIV patient group (34.6%) than the HIV control (2.2%) and non-HIV control (2.2%) groups, whereas HSV-2 IgG seroprevalence was higher in both HIV patient (61.5%) and HIV control (57.8%) groups than the non-HIV control group (17.8%). The prevalence of HSV-2 was significantly higher in persons with multiple partners and in the reproductive age group. The overall seroprevalence of HSV-1 IgM was too low (<5%), whereas it was too high (about 90%) with HSV-1 IgG in all three study groups. PMID- 26557850 TI - Effect of EDTA Conditioning and Carbodiimide Pretreatment on the Bonding Performance of All-in-One Self-Etch Adhesives. AB - Objective. This study evaluated the effect of ethylenediaminetetraacetic acid (EDTA) conditioning and carbodiimide (EDC) pretreatment on the shear bond strength of two all-in-one self-etch adhesives to dentin. Methods. Flat coronal dentin surfaces were prepared on one hundred and sixty extracted human molars. Teeth were randomly divided into eight groups according to two different self etch adhesives used [G-Bond and OptiBond-All-In-One] and four different surface pretreatments: (a) adhesive applied following manufacturer's instructions; (b) dentin conditioning with 24% EDTA gel prior to application of adhesive; (c) EDC pretreatment followed by application of adhesive; (d) application of EDC on EDTA conditioned dentin surface followed by application of adhesive. Composite restorations were placed in all the samples. Ten samples from each group were subjected to immediate and delayed (6-month storage in artificial saliva) shear bond strength evaluation. Data collected was subjected to statistical analysis using three-way ANOVA and post hoc Tukey's test at a significance level of p < 0.05. Results and Conclusion. EDTA preconditioning as well as EDC pretreatment alone had no significant effect on the immediate and delayed bond strengths of either of the adhesives. However, EDC pretreatment on EDTA conditioned dentin surface resulted in preservation of resin-dentin bond strength of both adhesives with no significant fall over six months. PMID- 26557851 TI - Impact of Digital Panoramic Radiograph Magnification on Vertical Measurement Accuracy. AB - Objectives. The purpose of this panoramic radiography study was to assess the impact of image magnification on the accuracy of vertical measurements in the posterior mandible. Methods. Six dental implants, inserted in the posterior segments of a resin model, were used as reference objects. Two observers performed implant length measurements using a proprietary viewer with two preset image magnifications: the low (1.9 : 1) and the medium (3.4 : 1) image magnifications. They also measured the implant lengths in two Digital Imaging Communications in Medicine viewers set at low (1.9 : 1), medium (3.4 : 1), and high (10 : 1) image magnifications. Results. The error between the measured length and the real implant length was close to zero for all three viewers and image magnifications. The percentage of measurements equal to the real implant length was the highest (83.3%) for the high image magnification and below 30% for all viewers with the low image magnification. Conclusions. The high and medium image magnifications used in this study allowed accurate vertical measurements, with all three imaging programs, in the posterior segments of a mandibular model. This study suggests that a low image magnification should not be used for vertical measurements on digital panoramic radiographs when planning an implant in the posterior mandible. PMID- 26557852 TI - Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T. AB - The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury. PMID- 26557853 TI - Are healthcare providers asking about environmental exposures? A community-based mixed methods study. AB - People living near environmental hazards may develop symptoms and health conditions that require specialized monitoring and treatment by healthcare providers. One emerging environmental hazard is coal ash. Coal ash is comprised of small particles containing heavy metals, polycyclic aromatic hydrocarbons, and radioactive elements. The overall purpose of this study was to explore whether healthcare providers ask patients if they live near an environmental hazard like coal ash storage sites and to assess what health conditions prompt a provider inquiry. Focus groups were conducted in 2012 and a cross-sectional survey was administered in 2013. Overall, 61% of survey respondents reported that their healthcare providers never asked if they lived near an environmental hazard. One focus group member stated "No, they don't ask that. They just always blame stuff on you...." Respondents with asthma and other lung conditions were significantly more likely to be asked by a healthcare provider if they lived near an environmental hazard. Due to the unique exposures from environmental hazards and the low prevalence of patients being asked about environmental hazards, we recommend that healthcare providers take environmental health histories in order to understand patients' exposures, to monitor symptoms of exposure, and to assist with education about reducing exposure. PMID- 26557854 TI - Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis. AB - Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-kappaB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-kappaB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID- 26557855 TI - Application of Antrodia camphorata Promotes Rat's Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro. AB - Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson's trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation. PMID- 26557856 TI - Expression of Caspase-1 Gene Transcript Variant mRNA in Peripheral Blood Mononuclear Cells of Patients with Primary Gout in Different TCM Syndromes. AB - A large number of studies have shown that cysteinyl aspartate specific protease-1 (CASP1) played an important role in the inflammatory response of primary gout, but the decreased expression of different CASP1 transcript variant could inhibit the activation of IL-1beta. Our study mainly analyzed the expression level and function of CASP1 gene transcript variant mRNA in peripheral blood mononuclear cells of patients with gout in different TCM syndromes. The expression of CASP1 gene transcript variant and IL-1beta mRNA in PBMCs were detected in patients with PG [acute phase (AP: 44 cases); nonacute phase (NAP: 52 cases)] and healthy controls (HC: 30 cases) by reverse transcription-polymerase chain reaction and/or real-time quantitative polymerase chain reaction. The expressions of plasma IL 1beta in patients with PG and HC were detected by enzyme-linked immunosorbent assay. Dysregulated expression of the CASP1 gene and its transcript variant, plasma proinflammatory cytokines in all patients with primary gout in different TCM syndromes, correlation analysis showed that there was negative correlation between the expression of CASP1-gamma gene transcript variant mRNA and IL-1beta protein in APPG group. The study suggested that CASP1 gene and its transcript variant may play a critical role in the inflammatory response of patients with PG in different phases and TCM syndromes. PMID- 26557857 TI - Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses. AB - Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus. Importantly, they demonstrate potent antiviral activities against drug-resistant strains. In the study of mechanisms, we found that Xiaoqinglong mixture could increase antiviral interferon production by activating p38 MAPK, JNK/SAPK pathway, and relative nuclear transcription factors. Lastly, our studies also indicate that some of these medicines show inhibitory activities against EV71 and CVB strains. In conclusion, the 10 traditional Chinese medicines, as kind of compound combination medicines, show broad-spectrum antiviral activities, possibly also including inhibitory activities against strains resistant to available antiviral drugs. PMID- 26557858 TI - Scutellarin Reduces Endothelium Dysfunction through the PKG-I Pathway. AB - Purpose. In this report, we investigated the protective mechanism of scutellarin (SCU) in vitro and in vivo which could be involved in endothelial cGMP-dependent protein kinase (PKG), vasodilator stimulated phosphoprotein (VASP) pathway, and vascular endothelium dysfunction (EtD). Method. Human brain microvascular endothelial cells (HBMECs) with hypoxia reoxygenation (HR) treatment and rats with cerebral ischemia reperfusion (CIR) treatment were applied. Protein and mRNA expression of PKG, VASP, and p-VASP were evaluated by Western blot and RT-PCR methods. Vascular EtD was assessed by using wire myography to determine endothelium-dependent vasorelaxation in isolated rat basilar artery (BA). Result. In cultured HBMECs, SCU (0.1, 1, and 10 MUM) increased cell viability, mRNA, protein level, and phosphorylative activity of PKG and VASP against HR injury. In HR model of BA, SCU increased protein level of P-VASP. In rat CIR model, wire myography demonstrated that SCU (45 and 90 mg/kg, i.v.) significantly reduced ischemic size by partially restoring the endothelium dependent vasodilation of BA; PKG inhibitor Rp-8-Br-cGMPS (50 MUg/kg, i.v.) reversed this protection of SCU in CIR rats. Conclusion. SCU protects against cerebral vascular EtD through endothelial PKG pathway activation. PMID- 26557859 TI - Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats. AB - The research tries to establish Wistar rat's model of atherosclerosis for evaluating the antiatherosclerotic effect of hederagenin and exploring its antiatherosclerosis-related mechanisms. The statistical data have shown that hederagenin exhibits multiple pharmacological activities in the treatment of hyperlipidemia, antiplatelet aggregation, liver protection, and anti inflammation, indicating that hederagenin may exert a protective effect on vascular walls by improving lipid metabolism disorders and lipid deposition. The results show that hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKbeta/NF-kappaB signaling pathway to reduce the release of IL 6, IFN-gamma, TNF-alpha, and other inflammatory factors. The experimental results indicated that hederagenin can inhibit or ameliorate the pathological changes associated with AS, displaying an excellent preventive function against AS. PMID- 26557860 TI - Medicinal Plants and Natural Active Compounds for Diabetes and/or Obesity Treatment. PMID- 26557861 TI - Effect of alpha-Allocryptopine on Delayed Afterdepolarizations and Triggered Activities in Mice Cardiomyocytes Treated with Isoproterenol. AB - Objective. To investigate the effect of alpha-allocryptopine (ALL) on delayed afterdepolarization (DAD) incidence and triggered activity (TA) in mice administered isoproterenol (ISO). Methods. Mouse ventricular myocytes were isolated. And the cellular electrophysiological properties of ventricular myocytes were investigated. Results. We found that the incidences of DADs and TA in mouse myocytes were increased by ISO treatment. In sharp contrast, triggered arrhythmia events were rarely observed in myocytes with 10 MUM ALL treatment. Transient inward current (I ti) was reduced significantly with ALL treatment, which contributed to DAD-related triggered arrhythmia. Compared to Iso-treated group, the L-type calcium current (I Ca,L) densities were decreased after exposure to ALL, along with slower activation, quicker inactivation, and longer time constant of recovery from inactivation kinetics. Conclusion. There is less triggered arrhythmia events in ventricular myocytes treated with ALL. This effect may be associated with the inhibition of I ti and I Ca,L. PMID- 26557862 TI - Phenolic Compounds from Olea europaea L. Possess Antioxidant Activity and Inhibit Carbohydrate Metabolizing Enzymes In Vitro. AB - Phenolic composition and biological activities of fruit extracts from Italian and Algerian Olea europaea L. cultivars were studied. Total phenolic and tannin contents were quantified in the extracts. Moreover 14 different phenolic compounds were identified, and their profiles showed remarkable quantitative differences among analysed extracts. Moreover antioxidant and enzymatic inhibition activities were studied. Three complementary assays were used to measure their antioxidant activities and consequently Relative Antioxidant Capacity Index (RACI) was used to compare and easily describe obtained results. Results showed that Chemlal, between Algerian cultivars, and Coratina, among Italian ones, had the highest RACI values. On the other hand all extracts and the most abundant phenolics were tested for their efficiency to inhibit alpha-amylase and alpha-glucosidase enzymes. Leccino, among all analysed cultivars, and luteolin, among identified phenolic compounds, were found to be the best inhibitors of alpha-amylase and alpha-glucosidase enzymes. Results demonstrated that Olea europaea fruit extracts can represent an important natural source with high antioxidant potential and significant alpha-amylase and alpha-glucosidase inhibitory effects. PMID- 26557863 TI - Nao-Xue-Shu Oral Liquid Improves Aphasia of Mixed Stroke. AB - Objective. The objective is to observe whether the traditional Chinese medicine (TCM) Nao-Xue-Shu oral liquid improves aphasia of mixed stroke. Methods. A total of 102 patients with aphasia of mixed stroke were divided into two groups by a single blind random method. The patients treated by standard Western medicine plus Nao-Xue-Shu oral liquid (n = 58) were assigned to the treatment group while the remaining patients treated only by standard Western medicine (n = 58) constituted the control group. Changes in the Western Aphasia Battery (WAB), Modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and hemorheology parameters were assessed to evaluate the effects of the treatments. Results. Excluding the patients who dropped out, 54 patients in the treatment group and 51 patients in the control group were used to evaluate the effects. Significant and persistent improvements in the WAB score, specifically comprehension, repetition, naming, and calculating, were found in the treatment group when the effects were evaluated at the end of week 2 and week 4, respectively, compared with baseline. The naming and writing scores were also improved at the end of week 4 in this group. The comprehension and reading scores were improved at the end of week 4 in the control group compared with the baseline, but the improvements were smaller than those in the treatment group. The percentages of patients at the 0-1 range of mRS were increased at the end of week 2 and week 4 in both groups, but the improvements in the treatment group were much larger than those in the control group. Greater improvements in the NIHSS scores and the hemorheology parameters in the treatment group were also observed compared with the control group at the end of week 2 and week 4. Conclusion. Nao-Xue-Shu oral liquid formulation improved aphasia in mixed stroke patients and thus might be a potentially effective drug for treating stroke aphasia. PMID- 26557864 TI - Polydatin Inhibits Formation of Macrophage-Derived Foam Cells. AB - Rhizoma Polygoni Cuspidati, a Chinese herbal medicine, has been widely used in traditional Chinese medicine for a long time. Polydatin, one of the major active ingredients in Rhizoma Polygoni Cuspidati, has been recently shown to possess extensive cardiovascular pharmacological activities. In present study, we examined the effects of Polydatin on the formation of peritoneal macrophage derived foam cells in Apolipoprotein E gene knockout mice (ApoE(-/-)) and explored the potential underlying mechanisms. Peritoneal macrophages were collected from ApoE(-/-) mice and cultured in vitro. These cells sequentially were divided into four groups: Control group, Model group, Lovastatin group, and Polydatin group. Our results demonstrated that Polydatin significantly inhibits the formation of foam cells derived from peritoneal macrophages. Further studies indicated that Polydatin regulates the metabolism of intracellular lipid and possesses anti-inflammatory effects, which may be regulated through the PPAR gamma signaling pathways. PMID- 26557865 TI - Characterizing Herbal Medicine Use for Noncommunicable Diseases in Urban South Africa. AB - Economic challenges associated with noncommunicable diseases (NCDs) and the sociocultural outlook of many patients especially in Africa have increased dependence on traditional herbal medicines (THMs) for these diseases. A cross sectional descriptive study designed to determine the prevalence of and reasons for THM use in the management of NCDs among South African adults was conducted in an urban, economically disadvantaged area of Cape Town, South Africa. In a cohort of 1030 participants recruited as part of the existing Prospective Urban and Rural Epidemiological (PURE) study, 456 individuals were identified. The overall prevalence of THM use was 27%, of which 61% was for NCDs. Participants used THM because of a family history (49%) and sociocultural beliefs (33%). Hypertensive medication was most commonly used concurrently with THM. Healthcare professionals need to be aware of the potential dualistic use of THM and conventional drugs by patients, as this could significantly influence health outcomes. Efforts should be made to educate patients on the potential for drug/herb interactions. PMID- 26557866 TI - The Metabonomic Studies of Tongue Coating in H. pylori Positive Chronic Gastritis Patients. AB - In Traditional Chinese Medicine (TCM), tongue diagnosis (TD) has been an important diagnostic method for the last 3000 years. Tongue coating can be used as a very sensitive marker to determine the progress of chronic gastritis. Therefore, the scientific, qualitative, and quantitative study for the pathophysiologic basis of tongue coating (TC) emerged as a major direction for the objective research of TD. In our current report, we used GC/MS technology to determine the potential changes of metabolites and identify special metabolic biomarkers in the TC of H. pylori infected chronic gastritis patients. Four discriminative metabolites were identified by GC/MS between the TC of H. pylori infection (G + H) and without H. pylori infection (G - H) patients: ethylene, cephaloridine, gamma-aminobutyric acid, and 5-pyroglutamic acid, indicating that changes in amino acid metabolism are possibly involved in the formation of TC, and the amino acid metabolites are part of the material components of TC in G + H patients. PMID- 26557867 TI - Evaluation of the Inhibitory Effects of Bavachinin and Bavachin on Human Monoamine Oxidases A and B. AB - Monoamine oxidase B inhibitors (MAO-BIs) are used in the early management of Parkinson's disease (PD). Long-term suspected side effects of MAO-B classical inhibitors established the need for safer alternative therapeutic agents. In our study, the flavanone bavachinin (BNN) and its analog bavachin (BVN) found in the seeds of Psoralea corylifolia L. ethanolic extract (PCSEE) were investigated for their human MAO-A and MAO-B (hMAO-A and hMAO-B) inhibition. Both PCSEE and BNN effectively reduced hMAO-B activity more than hMAO-A while BVN had activating effects. BNN showed selective hMAO-B inhibition (IC50 ~ 8.82 MUM) more than hMAO A (IC502009;~ 189.28 MUM). BNN in the crude extract was determined by HPLC, also validated by TLC showing a yield of 0.21% PCSEE dry weight. BNN competitively inhibited hMAO-A and hMAO-B, with a lower hMAO-B K i than hMAO-A K i by 10.33 fold, and reduced hMAO-B K m /V max efficiency ratio to be comparable to the standard selegiline. Molecular docking examination of BNN and BVN predicted an indirect role of BNN C7-methoxy group for its higher affinity, selectivity, and reversibility as an MAO-BI. These findings suggest that BNN, which is known to be a potent PPAR-gamma agonist, is a selective and competitive hMAO-B inhibitor and could be used in the management of PD. PMID- 26557868 TI - Yiqihuoxuejiedu Formula Restrains Vascular Remodeling by Reducing the Inflammation Reaction and Cx43 Expression in the Adventitia after Balloon Injury. AB - Vascular remodeling is closely related to hypertension, atherosclerosis, and restenosis after PCI. Considerable evidence indicates that the activation and proliferation of adventitial fibroblasts play key roles in vessel injury. The inflammatory response and high expression of connexins contribute to adventitial remodeling. Therefore, reducing inflammation reaction and connexins expression in adventitia may become a new target to prevent vascular remodeling. Yiqihuoxuejiedu formula, composed of TCM therapeutic principle of supplementing qi, activating blood and detoxification, can inhibit restenosis after intimal injury. To further investigate the effect of Yiqihuoxuejiedu formula on inflammation and connexins, we established a carotid artery injury model. In model rats, hyperplasia in the intima was mild but obvious in the adventitia; CRP heightened; expressions of MCP-1, CD68, and Cx43 increased. Yiqihuoxuejiedu formula relieved intimal hyperplasia and adventitial area, obviously diminished the expressions of CD68 and Cx43 in the adventitia, and reduced CRP but did not lower MCP-1. These results indicated that Yiqihuoxuejiedu formula inhibited vascular remodeling especially adventitial hyperplasia by reducing the inflammation reaction including lowering macrophages infiltration and systemic nonspecific inflammatory response and also restraining gap junction connexins leading to less communication among cells. This study provides new ideas and methods for the prevention and treatment of vascular remodeling. PMID- 26557869 TI - Recent Advance in Applications of Proteomics Technologies on Traditional Chinese Medicine Research. AB - Proteomics technology, a major component of system biology, has gained comprehensive attention in the area of medical diagnosis, drug development, and mechanism research. On the holistic and systemic theory, proteomics has a convergence with traditional Chinese medicine (TCM). In this review, we discussed the applications of proteomic technologies in diseases-TCM syndrome combination researches. We also introduced the proteomic studies on the in vivo and in vitro effects and underlying mechanisms of TCM treatments using Chinese herbal medicine (CHM), Chinese herbal formula (CHF), and acupuncture. Furthermore, the combined studies of proteomics with other "-omics" technologies in TCM were also discussed. In summary, this report presents an overview of the recent advances in the application of proteomic technologies in TCM studies and sheds a light on the future global and further research on TCM. PMID- 26557870 TI - Young male mating success is associated with sperm number but not with male sex pheromone titres. AB - BACKGROUND: Intraspecific communication is of crucial importance throughout the animal kingdom and may involve a combination of visual, gustatory, olfactory and acoustic cues. Variation in male sex pheromone amount and composition may convey important information to female conspecifics, for instance on species identity or age. However, whether increased male pheromone titres are associated with fitness benefits for the female, thus indicating a role as an honest signal, is under debate. RESULTS: Against this background, we tested in the butterfly Bicyclus anynana (1) whether young males being successful or unsuccessful in gaining a mating differed in sex pheromone titres and (2) for associations between male pheromone titres and spermatophore mass, eupyrene sperm number, and a variety of female and offspring life-history traits. Successful and unsuccessful males did not differ in pheromone titres, however eupyrene sperm number was much higher in successful males. Pheromone titres were not associated with any fitness-related female or offspring trait measured in our study, though correlation analyses yielded evidence for trade-offs among specific traits. Patterns did not differ among control and olfaction-blocked females. CONCLUSION: Therefore, we suggest that in young B. anynana pheromone titres do not indicate male quality. PMID- 26557871 TI - The Nonsubsampled Contourlet Transform Based Statistical Medical Image Fusion Using Generalized Gaussian Density. AB - We propose a novel medical image fusion scheme based on the statistical dependencies between coefficients in the nonsubsampled contourlet transform (NSCT) domain, in which the probability density function of the NSCT coefficients is concisely fitted using generalized Gaussian density (GGD), as well as the similarity measurement of two subbands is accurately computed by Jensen-Shannon divergence of two GGDs. To preserve more useful information from source images, the new fusion rules are developed to combine the subbands with the varied frequencies. That is, the low frequency subbands are fused by utilizing two activity measures based on the regional standard deviation and Shannon entropy and the high frequency subbands are merged together via weight maps which are determined by the saliency values of pixels. The experimental results demonstrate that the proposed method significantly outperforms the conventional NSCT based medical image fusion approaches in both visual perception and evaluation indices. PMID- 26557872 TI - International dissemination of evidence-based practice, open access and the IACAPAP textbook of child and adolescent mental health. AB - Dramatic changes have occurred in both publishing and teaching in the last 20 years stemming from the digital and Internet revolutions. Such changes are likely to grow exponentially in the near future aided by the trend to open access publishing. This revolution has challenged traditional publishing and teaching methods that-largely but not exclusively due to cost-are particularly relevant to professionals in low and middle income countries. The digital medium and the Internet offer boundless opportunities for teaching and training to people in disadvantaged regions. This article describes the development of the IACAPAP eTextbook of child and adolescent mental health, its use, accessibility, and potential impact on the international dissemination of evidence-based practice. PMID- 26557873 TI - Oncology pharmacy units: a safety policy for handling hazardous drugs and related waste in low- and middle-income African countries-Angolan experience. AB - In African countries, higher rates of late-stage cancers at the time of first diagnosis are a reality. In this context, hazardous drugs (HDs), such as chemotherapy, play an important role and have immense benefits for patients' treatment. HDs should be handled under specific conditions. At least a class 5 environment primary engineering control (PEC), physically located in an appropriate buffer area, is mandatory for sterile HDs compounding, as well as administrative control, personal protective equipment, work practices and other engineering and environmental controls, in order to protect the environment, patient, and worker. The aim of this study is to describe the Angolan experience regarding the development of oncology pharmacy units and discuss international evidence-based guidelines on handling HDs and related waste. Measures to incorporate modern and economical solutions to upgrade or build adequate and safe facilities and staff training, in order to comply with international guidelines in this area, are crucial tasks for African countries of low and middle income. PMID- 26557874 TI - Endoscopic inguinal lymphadenectomy in penile cancer: case report and literature review. AB - OBJECTIVES: The objective was to submit our first experience in endoscopic inguinal lymphadenectomy (EIL), evaluate the feasibility of the procedure and carry out a review of the literature. MATERIAL AND METHODS: A 41-year-old patient was diagnosed with penile cancer with squamous cell carcinoma pT2G1 pathology, with no palpable inguinal lymph nodes. A bilateral inguinal lymphadenectomy was performed with preservation of the saphenous vein, conventional left and endoscopic right procedures. The perioperative data is presented and that obtained is discussed in the literature. RESULTS: The total time was 270 minutes, 180 for endoscopic and 90 for conventional procedures. Blood loss was minimal in both cases. Fifteen lymph nodes were dissected on the endoscopic side, and 17 in the conventional side, the latter with more pain and devitalised skin flap. CONCLUSIONS: EIL for penile cancer is feasible and there is less morbidity with an early recovery. The literature is not conclusive on the indication of EIL. PMID- 26557875 TI - Epidemiology of cervical cancer in Latin America. AB - The basic aspects of the descriptive epidemiology of cervical cancer in Latin America are presented. A decrease in the incidence and mortality rates has been observed in the period from 2000 to 2012 in all countries across the region, this has not occurred at the same proportions, and in many countries, observed figures of incidence and mortality are among the highest levels in the world. In Latin America, calculating a mean measure of the numbers from the GLOBOCAN data from 2000 to 2012, we can observe a difference of up to fivefold of the incidence (Puerto Rico 9,73 Vs Bolivia 50,73) and almost seven times for mortality (Puerto Rico 3,3 Vs Nicaragua 21,67). A report of the epidemiology, risk factors, and evaluation of screening procedures regarding the possible impact of the human papillomavirus (HPV) vaccine I in the prevention of cervical cancer is presented. PMID- 26557876 TI - The cervical cancer prevention programme in Costa Rica. AB - Cervical and uterine cancer continues to be an important issue for women around the world, although neoplasia has the greatest demonstrated potential for prevention. Costa Rica has achieved important advances in the reduction of the incidence and mortality of these cancers since the last century. This is the result of a series of policies, programmes, and plans, not only at the level of the health care system, but also in other areas. Increased access for women to care in health centres, fundamentally at the primary level, has been vital, as has ensuring the quality of cytology readings and access to diagnosis and treatment for precursor lesions for in situ and invasive cancers. Despite all of these achievements, there are still challenges to be overcome, which are widespread in many countries in Latin America and the Caribbean. It is important to learn from the experiences of other countries in order to improve women's health not only as a health objective, but also as an ethical imperative to promote the exercise of women's rights to life and health. PMID- 26557877 TI - Persistent infection with high-risk human papilloma viruses: cohort study, Merida, Venezuela. AB - Cervical lesions have been associated with infection by high-risk human papilloma virus (high-risk HPV). In 409 women aged >15 years high-risk HPV lesions were identified. In a cohort of this population persistent infection was compared with cytological, colposcopic, and histological lesions. Cervical scrapes were taken and DNA was isolated. HPV was detected by PCR in the E6/E7 region. Genotyping was performed by PCR nested multiple E6/E7. HPV was detected in a 37.40% (153/409), high-risk HPV in 86% (153/178), HPV18 46.64% (83/178), HPV16 34.28% (61/178). Among these 53.93% (96/178) were multiple infections, and HPV18/16 (30/96) was the most frequent 31.25%. The cytology showed changes in 15% of positive patients. A 49.67% in women positive for HPV infection showed abnormalities in the colposcopic study, a relationship that turned out to be statistically significant ( p < 0.0019 test chi(2)). Among all 85% of the women were younger than 45 years of age. Fifty-seven patients were evaluated 15 months after the base study, with initial prevalence of morbidity 49.12% (28/57) and at the end 10.53% (6/57), showing in 89.29% (25/28) negative for HR-HPV infection, 10.34% (3/28) showed persistence of infection, 17.54% (10/57) presented cytological alterations, with 80% of positivity for HPV, and a regression of 100% (10/10) of the previously identified lesions. With colposcopy, 50% (14/28) presented alterations related to HPV, of these 85.71% (12/14) showed regression of such an alteration. The cumulative incidence for HPV was 10.34% (3/29). The incidence rate was 4.23% (3/71), which is equal to 4.23 new cases of HPV infection per 100 people, per year of follow-up. In conclusion, the present work shows a high frequency of infection by high-risk HPV, with predominance of HPV18 and 16 and in general for multiple infections. Colposcopy was better predictor than the Pap smear for infection. The follow-up study revealed a low percentage of persistent infection, and a high frequency of negativity for viral infection, high regression of cytological and colposcopic lesions, a low cumulative and incidence rate similar to that reported by other Latin American countries and higher than the European countries. PMID- 26557878 TI - Training in the prevention of cervical cancer: advantages of e-learning. AB - Cervical cancer remains the second most common cancer for women worldwide and is the cancer priority in most low- and middle-income countries (LMIC). The development of vaccines against the human papilloma virus (HPV) and the impact of technology both for the detection of HPV and cervical cancer represent milestones and new opportunities in prevention. New internet-based technologies are generating mass access to training programmes. This article presents the methodology for developing an online training programme for the prevention of cervical cancer as well as the results obtained during the four year period wherein the same programme was delivered in Latin America. PMID- 26557879 TI - Aspirin in the 21st century-common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK. AB - Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV. PMID- 26557881 TI - Characteristics of salivary gland tumours in the United Arab Emirates. AB - Salivary gland tumours (SGT) are relatively rare cancers characterised by striking morphological diversity and wide variation in the global distribution of SGT incidence. Given the proximity to the head and neck structures, management of SGT has been clinically difficult. To the best of our knowledge, there are no epidemiological studies on SGT from the United Arab Emirates (UAE) or the Gulf Cooperation Council Countries (GCC). Patient charts (N = 314) and associated pathological records were systematically reviewed between the years 1998-2014. Predominance of benign (74%) compared with malignant (26%) SGT was observed. Among the 83 malignant SGT identified, frequency was higher in males (61%) than in females (39%) and peak occurrence was in the fifth decade of life. Mucoepidermoid carcinoma was the most common type of tumour (35%) followed by adenoid cystic carcinoma (18.1%) and acinar cell carcinoma (10.8%). A similar pattern of tumour distribution was seen in patients from GCC, Asian, and Middle East countries. This is the first report to address the distribution of salivary gland tumours in a multiethnic, multicultural population of the Gulf. The results suggest that the development of an SGT registry will help clinicians and researchers to better understand, manage, and treat this rare disease. PMID- 26557880 TI - Effectiveness and safety of monoclonal antibodies for metastatic colorectal cancer treatment: systematic review and meta-analysis. AB - BACKGROUND: The effectiveness of chemotherapy (CT) for select cases of metastatic colorectal cancer (MCRC) has been well established in the literature, however, it provides limited benefits and in many cases constitutes a treatment with high toxicity. The use of specific molecular biological treatments with monoclonal antibodies (MA) has been shown to be relevant, particularly for its potential for increasing the response rate of the host to the tumour, as these have molecular targets present in the cancerous cells and their microenvironment thereby blocking their development. The combination of MA and CT can bring a significant increase in the rate of resectability of metastases, the progression-free survival (PFS), and the global survival (GS) in MCRC patients. OBJECTIVE: To assess the effectiveness and safety of MA in the treatment of MCRC. METHODS: A systematic review was carried out with a meta-analysis of randomised clinical trials comparing the use of cetuximab, bevacizumab, and panitumumab in the treatment of MCRC. RESULTS: Sixteen randomised clinical trials were selected. The quality of the evidence on the question was considered moderate and data from eight randomised clinical trials were included in this meta-analysis. The GS and PFS were greater in the groups which received the MA associated with CT, however, the differences were not statistically significant between the groups (mean of 17.7 months versus 17.1 months; mean difference of 1.09 (CI: 0.10-2.07); p = 0.84; and 7.4 versus 6.9 months. mean difference of 0.76 (CI: 0.08-1.44); p = 0.14 respectively). The meta-analysis was not done for any of the secondary outcomes. CONCLUSION: The addition of MA to CT for patients with metastatic colorectal cancer does not prolong GS and PFS. PMID- 26557882 TI - Medical treatment of early stage and rare histological variants of epithelial ovarian cancer. AB - Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient's performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients' quality of life. PMID- 26557883 TI - Anti-androgenic effects of flavonols in prostate cancer. AB - Dietary-derived agents, such as the flavonoids, are of particular interest for prostate cancer (PCa) chemoprevention as they may offer a favourable safety and side-effect profile. An agent that demonstrates action on the androgen receptor (AR) axis may have value for preventing or treating castrate-resistant PCa. Four main flavonols - quercetin, myricetin, kaempferol, and fisetin - have been demonstrated in laboratory studies to have chemopreventive action in both castrate-resistant and castrate-sensitive PCa models. Mechanisms of flavonol action on the AR axis in PCa have been proposed to be inhibition of the 5alpha reductase enzymes, direct androgen competition, suppression of the AR complex and transactivation by coregulators such as c-Jun, Sp1, and the PI3K/Akt pathway. It is, however, still unclear with current levels of evidence whether AR axis mediated effects can fully account for the flavonols' chemopreventive action. PMID- 26557884 TI - Safety and efficacy of the combination of T-DM1 with radiotherapy of the central nervous system in a patient with HER2-positive metastatic breast cancer: case study and review of the literature. AB - Approximately 35% of patients with confirmed HER2 breast cancer progress to metastases of the central nervous system (CNS). Total cerebral radiotherapy is considered as standard treatment for these cases; however, studies have shown that some chemotherapy drugs can be used during radiotherapy without significantly increasing its toxicity. In this article, we report the case of a patient with HER2-positive breast cancer who showed isolated progression of the illness in the CNS, which was observed during the treatment period using T-DM1 concomitantly with radiotherapy of the CNS without apparent toxicity of the combination and keeping the illness controlled. Through a review of the literature on the use of radiotherapy and chemotherapy with T-DM1 for the treatment of cerebral metastases in HER2-positive breast cancer, we describe the efficacy and tolerance of the concomitant application of these treatments. PMID- 26557885 TI - Costs of breast cancer care in Mexico: analysis of two insurance coverage scenarios. AB - BACKGROUND: Breast cancer (BC) is a major cause of disease and death worldwide. In addition to its contribution to mortality and disability, it is a major economic burden both public and private. OBJECTIVE: To estimate the average direct medical cost/year of care for the diagnosis and treatment of BC in two coverage scenarios in Mexico: What is 'ideal' based on service usage patterns according to international guidelines and what is 'current' using the service usage patterns of suppliers in Mexico. MATERIAL AND METHODS: The pattern and intensity of use of procedures for the care of BC in the Mexican Social Security Institute (IMSS) for 2009 were identified and prices were associated using the guidelines from the System of Social Protection in Health (SPSS) and the IMSS for the current scenario and the ideal scenario, international patterns (Breast Health Global Initiative BHGI after its acronym in English) were used and prices were associated from the SPSS guidelines. RESULTS: The annual average direct medical cost per patient in the 'current' scenario was 8557 US$, while the cost in the 'ideal' scenario was 4554 US$. There are differences in costs between 'what we do' and 'what should be done', due to differences in the implementation of the interventions for the treatment of the different stages of the disease. A proportional increase in the average cost was also identified as the diagnosis stage advanced (from I to III). CONCLUSIONS: Given that in Mexico there is universal insurance coverage for the treatment of BC, it is necessary to use economic resources more efficiently. It is necessary to continue to examine this topic in more depth and the next step will be to assess the effectiveness of both scenarios in order to provide enough evidence for the decision-making process. PMID- 26557886 TI - Cancer, obesity, and legitimation of suggested lifestyles: a libertarian paternalism approach. AB - We know that around 30% of all cancers are preventable. We also know that there is clear evidence of the causal relations between obesity and cancer. This means that there could be lifestyles that could prevent obesity and, thus, cancer. Yet, who legitimises these lifestyles and on which ground? Should citizens be free to accept or not to accept policies concerning them? This is a problem faced within what has been named libertarian paternalism. We discuss it, also proposing a version that we call deliberative libertarian paternalism, showing how important this problem is for a proper framing of the lifestyle policies concerning obesity and, thus, cancer prevention. PMID- 26557887 TI - The wisdom of crowds and the repurposing of artesunate as an anticancer drug. AB - Artesunate, a semi-synthetic and water-soluble artemisinin-derivative used as an anti-malarial agent, has attracted the attention of cancer researchers due to a broad range of anti-cancer activity including anti-angiogenic, immunomodulatory and treatment-sensitisation effects. In addition to pre-clinical evidence in a range of cancers, a recently completed randomised blinded trial in colorectal cancer has provided a positive signal for further clinical investigation. Used perioperatively artesunate appears to reduce the rate of disease recurrence - and the Neo-Art trial, a larger Phase II RCT, is seeking to confirm this positive effect. However, artesunate is a generic medication, and as with other trials of repurposed drugs, the Neo-Art trial does not have commercial sponsorship. In an innovative move, the trial is seeking funds directly from members of the public via a crowd-funding strategy that may have resonance beyond this single trial. PMID- 26557888 TI - Daytime intragastric acid control: post hoc analyses of esomeprazole 20 mg and over-the-counter proton-pump inhibitors. AB - OBJECTIVES: In mild gastroesophageal reflux disease, which accounts for the great majority of cases, the major burden of reflux occurs during daytime hours, after food intake. The aim of these analyses was to evaluate intragastric pH control during the typical 14-hour daytime awake period by proton-pump inhibitors (PPIs) given at over-the-counter (OTC) dosages. METHODS: In one double-blind and three open-label, randomized, crossover studies, intragastric pH was monitored for 24 hours on day 5 of treatment. The 24-hour data have been reported previously. Post hoc analyses reassessed these studies for the 14-hour daytime period, comparing esomeprazole 20 mg with currently available OTC PPIs omeprazole, pantoprazole (not available in the US) and lansoprazole. RESULTS: Subjects maintained intragastric pH >4 for a significantly greater mean percentage of the 14-hour daytime period with esomeprazole 20 mg compared with any of the PPI comparators at OTC dosages. Geometric mean ratios (95% confidence intervals) for esomeprazole 20 mg versus the comparators were: 1.45 (1.14-1.85; p = 0.003) versus omeprazole 20 mg; 2.50 (2.01-3.11; p < 0.0001) versus pantoprazole 20 mg; and 1.69 (1.46 1.97; p < 0.0001) and 1.89 (1.05-3.37; p = 0.03) versus lansoprazole 15 mg. A greater proportion of subjects had better pH control with esomeprazole than with the other PPIs (range: 69-97%). CONCLUSIONS: Across the 14-hour daytime period, esomeprazole 20 mg once daily given 30 minutes before breakfast for 5 days provided acid control for a significantly greater average proportion of time versus the PPI comparators omeprazole, pantoprazole and lansoprazole at currently available OTC dosages. PMID- 26557889 TI - Management of inflammatory bowel disease with oral serum-derived bovine immunoglobulin. AB - INTRODUCTION: The clinical effect of oral serum-derived bovine immunoglobulin/protein isolate (SBI) on symptom and disease management in patients with inflammatory bowel disease (IBD) is reported in this retrospective case series. METHODS: A single-center, retrospective chart review of IBD patients [N = 45; Crohn's disease (CD), n = 38 and ulcerative colitis (UC), n = 7] with limited to no response to traditional pharmaceutical therapies in controlling symptoms was performed after providing SBI (5 g/day) for nutritional support. Patients were contacted at least monthly to assess response to SBI for symptom management measured by a Likert scale (0 = none; 1 = minimal; 2 = moderate; 3 = significant; 4 = complete). Analysis of variance (ANOVA) was performed on response to therapy based on patient characteristics (age, gender, race) and IBD diagnosis. A multivariate ordered logistical regression model was performed to determine the odds ratio in overall disease management between week 1 and week 12. Finally, the overall group response and percent improvement to SBI was determined over 12 weeks. RESULTS: The odds ratio from the regression model demonstrated that IBD patients were 2.8 times more likely to report clinical improvement in symptom scores with the addition of SBI to their therapeutic regimens [95% confidence interval (CI) 1.266-6.016, p = 0.011]. Disease management was not significantly associated with age, gender, race or disease state. The percentage of patients reporting a response to SBI therapy at week 1 was 49% which increased to 76% after 12 weeks with the fraction of responders gaining significant symptom improvement doubling during the same time period (9% versus 20%). Overall, this group of IBD patients showed increased, steady response to SBI therapy between week 1 and 12 with no reported side effects. CONCLUSION: These results suggest that SBI improves clinical management of IBD patients who are not fully managed on traditional therapies. SBI should be considered for the nutritional support of IBD regardless of disease activity, location, phenotype, duration, or complexity. PMID- 26557890 TI - Combined radiological-endoscopic management of difficult bile duct stones: 18 year single center experience. AB - OBJECTIVES: Clinical evidence regarding radiological-endoscopic management of intrahepatic bile duct stones is currently lacking. Our aim is to report our 18 year experience in combined radiological-endoscopic management of intrahepatic difficult bile duct stones. METHODS: From June 1994 to June 2012, 299 symptomatic patients with difficult bile duct stones were admitted to our institution. Percutaneous transhepatic cholangiography (PTC)/biliary drainage/s was performed, dilating the PTC track to 10 or 16 French within 3-7 days. Afterward we carried out percutaneous transhepatic cholangioscopy (PTCS) with electrohydraulic lithotripsy (EHL) and/or interventional radiology techniques. Follow up was made with clinical/laboratory tests and ultrasound (US). We retrospectively analyzed our radiological-endoscopic approach and reported our technical and clinical outcomes. RESULTS: Complete stone clearance was achieved in 298 patients after a maximum of 4 consecutive sessions. Most patients (64.6%) were treated with PTCS/EHL alone, while the remaining with radiological techniques alone (26%) or a combination of both techniques (13.3%). Recurrence of stones occurred in 45 cases (15%, Tsunoda class III and class IV) within 2 years and were successfully retreated. Major adverse events were: 5 (1.6%) cases of massive bleeding that required embolisation, 2 (0.66%) perforations of the common bile duct and 31 cases (10.3%) of acute cholangitis managed with medical therapy or intervention. CONCLUSION: After 18 years of experience we demonstrated that our combined radiological-endoscopic approach to 'difficult bile duct stones' may result in both immediate and long-term clearance of stones with a low rate of adverse events. PMID- 26557891 TI - Crohn's disease: a clinical update. AB - Crohn's disease is increasing in prevalence worldwide. It arises from a complex interplay between both genetic predisposition and environmental influence. A search of databases and clinical practice guidelines was performed to provide the most up-to-date evidence-based approach for diagnosing and managing patients with Crohn's disease. No single gold standard investigation exists. Whilst full ileocolonoscopy with biopsies remains the mainstay for diagnosis, other less invasive imaging modalities are being actively considered in the workup, as well as the use of serological markers. Management should incorporate dietary and lifestyle modifications where necessary, the use of medications in induction and remission of disease, and consideration of surgical intervention where medical therapy has failed. PMID- 26557893 TI - Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. AB - Ramucirumab, a fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor 2, is the first targeted agent to have demonstrated an improvement in survival, as a single agent or in combination, in a molecularly unselected population in gastro-oesophageal cancer. Now that second line treatment is routinely considered for patients with advanced gastro oesophageal cancer, ramucirumab, with its favourable toxicity profile compared with cytotoxic treatment, provides a valuable additional treatment option. PMID- 26557892 TI - Evolving paradigms in the treatment of opioid-induced bowel dysfunction. AB - In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research. PMID- 26557894 TI - Therapeutic potential of ultrasound microbubbles in gastrointestinal oncology: recent advances and future prospects. AB - Microbubbles were initially invented as contrast agents for ultrasound imaging. However, lately more and more therapeutic applications of microbubbles are emerging, mostly related to drug and gene delivery. Ultrasound is a safe and noninvasive therapeutic modality which has the unique ability to interact with microbubbles and release their payload in situ in addition to permeabilizing the target tissues. The combination of drug-loaded microbubbles and ultrasound has been used in preclinical studies on blood-brain barrier opening, drug and gene delivery to solid tumors, and ablation of blood vessels. This review covers the basic principles of ultrasound-microbubble interaction, the types of microbubbles and the effect they have on tissue, and the preclinical and clinical experience with this approach to date in the field of gastrointestinal oncology. PMID- 26557896 TI - The effect of disease-modifying therapies on brain atrophy in patients with clinically isolated syndrome: a systematic review and meta-analysis. AB - OBJECTIVES: Brain atrophy is associated with cognitive deficits in patients with clinically isolated syndrome (CIS) and can predict conversion to clinical definite multiple sclerosis. The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMDs) on brain atrophy in patients with CIS. METHODS: Eligible placebo-control randomized clinical trials of patients with CIS that had reported changes in brain volume during the study period were identified by searching the MEDLINE, SCOPUS, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. This meta-analysis adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses. RESULTS: Three eligible studies were identified, comprising 1362 patients. The mean percentage change in brain volume was found to be significantly lower in DMD-treated patients versus placebo treated subgroups (standardized mean difference [SMD]: = -0.13, 95% confidence interval [CI]: -0.25, 0.01; p = 0.04). In the subgroup analysis of the two studies that provided data on brain-volume changes for the first (0-12 months) and second (13-24 months) year of treatment, DMD attenuated brain-volume loss in comparison with placebo during the second year (SMD = -0.25; 95% CI: -0.43, 0.07; p < 0.001), but not during the first year of treatment (SMD = -0.01; 95% CI: -0.27, 0.24; p = 0.93). No evidence of heterogeneity was found between estimates, while funnel-plot inspection revealed no evidence of publication bias. CONCLUSIONS: DMDs appear to attenuate brain atrophy over time in patients with CIS. The effect of DMDs on brain-volume loss is evident after the first year of treatment. PMID- 26557898 TI - Tumefactive multiple sclerosis lesions in two patients after cessation of fingolimod treatment. AB - BACKGROUND: Fingolimod (FTY) is the first oral medication approved for multiple sclerosis therapy. Until now, little has been known about the effects of FTY withdrawal regarding disease activity and development of tumefactive demyelinating lesions (TDLs), as already described in patients who discontinue natalizumab. METHODS: In this study we present the clinical and radiological findings of two patients who had a severe rebound after FTY withdrawal and compare these with patients identified by a PubMed data bank analysis using the search term 'fingolimod rebound'. In total, 10 patients, of whom three developed TDLs, are presented. RESULTS: Patients suffering from TDLs were free of clinical and radiological signs of disease activity under FTY therapy (100% versus 57%, compared with patients without TDLs) and had rebounds after a mean of 14.6 weeks (standard deviation 11.5) [patients without TDLs 11.7 (standard deviation 3.4)]. CONCLUSION: We propose that a good therapeutic response to FTY might be predisposing for a severe rebound after withdrawal. Consequently, therapy switches should be planned carefully with a short therapy free interval. PMID- 26557897 TI - Optimizing the initial choice and timing of therapy in relapsing-remitting multiple sclerosis. AB - With 12 available US Food and Drug Administration approved medications for the treatment of relapsing multiple sclerosis (MS), choosing an initial therapy is no longer a straightforward task. Each disease-modifying therapy (DMT) has a distinct risk-benefit profile and each patient is an individual. Therefore, the development of a simple algorithm to apply in selecting initial therapy is not feasible. Instead, the prescribing physician must consider many factors related to the treatments themselves, such as efficacy, safety, and tolerability, while also taking into account a particular patient's disease characteristics, personal preferences, comorbid illnesses and reproductive plans. The efficacy of each drug may be assessed through clinical trial data, although these data are limited by scarcity of direct comparisons among the different agents and lack of availability of biomarkers to predict an individual patient's response. Differences in safety profiles help to distinguish the various DMTs and influence selection of agent; both the known safety concerns, which can be addressed with risk mitigation and monitoring strategies, and the potential for yet undiscovered safety issues must be assessed, and an individual patient's comfort level with the risks and ability to comply with monitoring must be determined. Potential issues related to tolerability, which largely relate to matters of patient personal preference and lifestyle, should also be factored into the decision making process. With regard to the timing of therapy initiation, it must be acknowledged that long-term benefits of early DMT have not yet been definitively demonstrated. Nonetheless, starting DMT early in the MS disease course has been shown to have a beneficial effect on relapse prevention, and appears to curtail the atrophy and neurodegenerative changes that are now known to begin at disease onset. Although under certain circumstances there are acceptable reasons for deferring treatment, it is generally recommended that DMT is initiated early in the disease course. PMID- 26557899 TI - Optimal management of hormone receptor positive metastatic breast cancer in 2016. AB - Hormone receptor positive tumors represent the most common form of breast cancer and account for most of the deaths from the disease. Endocrine therapy represents the main initial therapeutic strategy for these patients and has been associated with significant clinical benefits in a majority of patients. While in early stages endocrine therapy is administered as part of a curative approach once clinical metastases develop, the disease is considered incurable and the main management objectives are tumor control and quality of life. The two major clinical paradigms of always indicating endocrine therapy in the absence of visceral crises and sequencing endocrine treatments have been guiding our therapeutic approach to these patients. However, for many decades, we have delivered endocrine therapy with a 'one size fits all' approach by applying agents that interfere with hormone receptor signaling equally in every clinical patient scenario. We have been unable to incorporate the well-known biologic principle of different degrees of hormone receptor dependency in our therapeutic recommendations. Recent developments in the understanding of molecular interactions of hormone signaling with other important growth factor, metabolic and cell division pathways have opened the possibility of improving results by modulating hormone signaling and interfering with resistance mechanisms yet to be fully understood. Unfortunately, limitations in the design of trials conducted in this area have made it difficult to develop predictive biomarkers and most of the new combinations with targeted agents, even though showing improvements in clinical endpoints, have been directed to an unselected population of patients. In this review we explore some of the current and most relevant literature in the management of hormone receptor positive advance breast cancer. PMID- 26557900 TI - Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options. AB - Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) remains an incurable disease, and approximately 25% of patients with HER2+ early breast cancer still relapse after adjuvant trastuzumab-based treatment. HER2 is a validated therapeutic target that remains relevant throughout the disease process. Recently, a number of novel HER2 targeted agents have become available, including lapatinib (a small molecule tyrosine kinase inhibitor of both HER2 and the epidermal growth factor receptor), pertuzumab (a new anti-HER2 monoclonal antibody) and ado-trastuzumab emtansine (T-DM1, a novel antibody-drug conjugate), which provide additional treatment options for patients with HER2+ MBC. The latest clinical trials have demonstrated improved outcome with treatment including pertuzumab or T-DM1 compared with standard HER2 targeted therapy. Here we review the clinical development of approved and investigational targeted agents for the treatment of HER2+ MBC, summarize the latest results of important clinical trials supporting use of these agents in the treatment of HER2+ MBC, and discuss how these results impact therapeutic options in clinical practice. PMID- 26557901 TI - Therapeutic potential of TAS-102 in the treatment of gastrointestinal malignancies. AB - Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda(r)). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer. PMID- 26557903 TI - Prognosis and segment-specific nodal spread of primary lung cancer in the right lower lobe. AB - BACKGROUND: Although lobe-specific nodal spread of primary lung cancer has been recently described, segment-specific nodal spread remains unclear. We investigated the frequency of hailer and mediastinal lymph node involvement and survival in patients with tumors located in the superior segment (SS) and basal segment (BS) in the right lower lobe. METHODS: Two hundred and sixty-three patients with primary lung cancer originating in the right lower lobe underwent lobectomy with systematic mediastinal lymph node dissection. Patients were categorized into two groups: SS (n = 114) or BS (n = 149). RESULTS: Frequencies of metastasis to station 11s and 11i were significantly higher in the SS (P < 0.0001) and BS groups (P = 0.022), respectively. Both the SS and BS groups showed a high frequency of subcarinal mediastinal zone (station 7) metastasis (96.9% and 90.6%, respectively; P = 0.271). The frequencies of superior mediastinal zone (station 2R and 4R) metastasis were 37.5% in the SS and 35.8% in the BS group (P = 0.878). In patients with pN2 disease, three-year disease-free survival was significantly shorter in the SS (22.6%) than the BS group (42.1%; P = 0.020). In the BS group, the independent predictive factors of a poor or good prognosis were metastasis to station 11i or skip metastasis, respectively; however, we did not detect an independent prognostic factor in the SS group. In the right lower lung lobe, there was no segment-specific nodal spread. CONCLUSION: When segmentectomy is undertaken, mediastinal lymph node dissection should be performed in proportion to lobectomy. PMID- 26557902 TI - Translational progress on tumor biomarkers. AB - There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine. PMID- 26557905 TI - Usefulness of positron emission tomography-computed tomography in pre-operative evaluation of intra-thoracic esophageal cancer. AB - BACKGROUND: The purpose of the study was to clarify the usefulness of positron emission tomography-computed tomography (PET-CT) for pre-operative evaluation of intra-thoracic esophageal cancer, especially in terms of regional lymph node status. METHODS: Medical records of 93 consecutive cases from July 2007 to October 2012 were retrospectively reviewed. All patients underwent curative and complete esophagectomies for intra-thoracic esophageal cancer. We compared pre operative maximum standard uptake values (SUVmax) of esophageal tumors and regional lymph nodes (LN) with other variables (chronic obstructive pulmonary disease, history of previous other primary cancer, gender, differentiation, and neoadjuvant therapy). In addition, the SUVmax of tumors and LNs were analyzed with pathologic findings. RESULTS: There was no significant difference of each tumor and LN SUVmax according to factors including chronic lung disease, age, history of previous other cancer, differentiation, and gender. Pre-operative evaluations by PET-CT were not accurate (tumor sensitivity 76.4%, specificity 25%; LN sensitivity 45.2%, specificity 54.8%). Receiver operating characteristic analysis showed that LN metastasis could not be appropriately diagnosed with SUVmax (P = 0.871). There was no difference in SUVmax between pathologically positive and negative LN subgroups. Tumor SUVmax correlated with the progression of esophageal cancer in patients without neoadjuvant therapy (P < 0.001). However, LN SUVmax had no correlation with overall pathologic stage. After neoadjuvant therapy, there were significant decreases in SUVmax in both pathologically positive and negative LN subgroups (P = 0.043, P = 0.008). CONCLUSION: Surgery should not be withheld in N-stage according to PET-CT findings and carefully considered in conjunction with other conditions. PMID- 26557904 TI - Subsequent treatment of epidermal growth factor receptor-tyrosine kinase inhibitor failure in patients with advanced lung adenocarcinoma. AB - BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) effectively treat advanced non-small cell lung cancer with EGFR-mutation. However, most patients develop acquired resistance without effective therapy subsequent to EGFR-TKI failure. We evaluated the efficacy of subsequent treatment strategies for EGFR-TKI resistance. METHODS: We retrospectively analyzed 240 patients with advanced lung adenocarcinoma with EGFR-TKI failure and following subsequent treatment. According to the first subsequent strategies after EGFR-TKI failure, patients were divided into groups of EGFR-TKI continuation (21 cases), EGFR-TKI continuation with chemotherapy (23 cases), chemotherapy alone (143 cases), and best supportive care (BSC) (53 cases). RESULTS: Except for 53 cases of BSC, the disease control rates (DCR) of the remaining 187 patients in the EGFR TKI continuation, EGFR-TKI continuation with chemotherapy, and chemotherapy alone groups were 66.7%, 73.9%, and 44.8%, respectively. The median post-progression progression-free survival (PFS) for the three groups was 3.0, 3.3, and 2.0 months, respectively. The DCR for the EGFR-TKI continuation with chemotherapy group was significantly higher than the chemotherapy alone group (P = 0.006). The post-progression PFS of the EGFR-TKI continuation with chemotherapy group was significantly longer than the chemotherapy alone group (P = 0.037). The median overall survival in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, chemotherapy alone, and BSC groups were 6.9, 11.6, 8.8, and 0.9 months, respectively. Compared to the BSC group, all groups achieved a survival benefit (P < 0.001). CONCLUSIONS: EGFR-TKI continuation with chemotherapy could provide benefits for patients with acquired resistance to EGFR-TKI. PMID- 26557907 TI - Analysis of lymph node impact on conversion of complete thoracoscopic lobectomy to open thoracotomy. AB - BACKGROUND: The aim of the study was to analyze the influence of lymph nodes in conversion thoracotomy and its measurements. METHOD: Between September 2006 to April 2013, 1006 patients (545 men, 461 women, median age 60 years, range: 13 to 86 years) received a complete thoracoscopic lobectomy. The main procedure was complete video-assisted anatomical lobectomy with mediastinal lymphadenectomy. RESULTS: All procedures were carried out smoothly without serious complication. Eighty-three cases were converted to thoracotomy (8.2%), including 70 cases of initiative conversion and 13 of passive conversion, in which 59 cases had interference by doornail lymph nodes. The average operative time was significantly longer (272.7 +/- 67.2 vs. 186.9 +/- 58.1 minutes, P = 0.001); the average blood loss was significantly increased (564.2 +/- 507.7 ml vs. 158.0 +/- 121.0 ml, P = 0.001); and the drainage time and postoperative hospital stay were significantly longer (8.9 +/- 5.0 vs. 6.6 +/- 3.5 days, P = 0.001; 12.5 +/- 7.7 vs. 9.2 +/- 5.8 days, P = 0.001, respectively) in the conversion thoracotomy compared with the complete endoscopic surgery group. CONCLUSION: Interference of the lymph nodes was the main reason for conversion to thoracotomy on video assisted thoracoscopic lobectomy, which prolonged operative time, increased the blood loss during surgery, and delayed postoperative recovery. Selecting the proper indication of conversion thoracotomy may reduce the negative effects. PMID- 26557906 TI - Activated estrogen receptor-mitogen-activated protein kinases cross talk confer acquired resistance to lapatinib. AB - BACKGROUND: The efficacy of lapatinib is limited by the development of acquired resistance. The aim of this study was to investigate the role of estrogen receptor (ER) signaling compensatory activation in acquired resistance to lapatinib in breast cancer cells BT474 and the related mechanism. METHODS: Acquired resistant cell model resistant (r)BT474 was generated with an increasing concentration of lapatinib. Real-time polymerase chain reaction and Western blotting were used to determine the changes of human epidermal growth factor receptor (HER)2 and ER pathways in breast cancer cell BT474 after treatment with lapatinib and the distinction between BT474 and rBT474. Methyl thiazolyl tetrazolium and colony formation assays were employed to detect the proliferation of rBT474 and BT474 cells treated with lapatinib and/or an ER inhibitor, fulvestrant, respectively. RESULTS: Lapatinib could inhibit phosphorylation of HER2 and induce expression of forkhead-box protein O3a and progesterone receptor. Acquired resistant cell model rBT474 could grow in the presence of 5 MUM lapatinib, with an apoptosis rate of only 5%. Significant inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) pathway and the activation of the mitogen-activated protein kinases (MAPK) and ER pathways were detected in rBT474, compared with BT474. Furthermore, the expressions of Src phosphorylation and caveolin-1 were also upregulated. The viability of rBT474 was markedly suppressed by the lapatinib/fulvestrant combination in vitro, confirmed by the BT474 xenograft model. CONCLUSION: ER signaling compensatory activation may partly contribute to lapatinib acquired resistance in HER2-overexpressing/ERalpha-positive breast cancer cells, which might be related to PI3K/AKT inhibition and MAPK pathway activation. PMID- 26557908 TI - Efficacy of bronchoscopic biopsy for the detection of epidermal growth factor receptor mutations and anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma. AB - BACKGROUND: To explore the efficacy of bronchoscopic biopsy for the detection of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in lung adenocarcinoma. METHODS: All patients with bronchoscopic biopsy-proven lung adenocarcinoma at the Peking Union Medical College Hospital from January 2009 to November 2011 were enrolled. Scorpion amplification refractory mutation system (ARMS) was used to detect EGFR gene mutations and fluorescence in situ hybridization (FISH) to detect ALK rearrangement. The correlation of immunohistochemistry (IHC) results with standard methods for EGFR mutation status and ALK rearrangement were checked. RESULTS: Bronchoscopic specimens were successfully used to detect EGFR mutation and ALK rearrangement with success rates of 85.2% and 71.3%, respectively, in non small cell lung cancer patients. EGFR analysis by ARMS yielded a positive result in 35.8% (33/92) and positive ALK rearrangement was detected by FISH in 7.8% (6/77) of cases. It was more likely to be unsuccessful in patients with tumor cells less than 100/high power field and the ratio tumor numbers in 0-10%. In EGFR-IHC, the sensitivity and specificity of E746-A750 deletions were 73.3% (11/15) and 93.3% (70/75), respectively, and those of L858R were 93.3% (14/15) and 93.2% (69/74), respectively. In ALK-IHC, the sensitivity and specificity were 50% (3/6) and 100% (71/71), respectively. CONCLUSIONS: Small bronchoscopic specimens could achieve higher successful detection rates via EGFR mutation and ALK gene rearrangement. PMID- 26557909 TI - Decreased expression of 14-3-3 sigma, an early event of malignant transformation of respiratory epithelium, also facilitates progression of squamous cell lung cancer. AB - BACKGROUND: It has been shown that 14-3-3 sigma serves as a tumor suppressor gene, and is downregulated in various tumor tissues. However, the role of 14-3-3 sigma during the initiation and progression of lung squamous cell carcinoma (SqCC) is not well understood. METHODS: The expression status of 14-3-3 sigma in archival tissue samples from 40 lung SqCC patients (36 with normal bronchia, 19 squamous metaplasia, and 17 dysplasia/carcinoma in situ, in their tissue samples) was examined by immunohistochemical analysis. The proliferation rate and tumor formation ability of the H520 cell transfected with 14-3-3 sigma was tested with methyl thiazolyl tetrazolium assay and nude mice subcutaneous injection, respectively. RESULTS: In the normal bronchial epithelia, 14-3-3 sigma was highly expressed, whereas it was significantly decreased in precancerous and cancerous tissues. Compared with matched invasive cancer tissues, the expression level of 14-3-3 sigma in squamous metaplasia was significantly higher (P = 0.049), while that in dysplasia/carcinoma in situ showed no significant changes (P = 0.135). Statistical analysis showed that the expression level of 14-3-3 sigma in tumor tissue was associated with the differentiation grade of the tumor (P = 0.001) and the prognosis of the patient (P = 0.003). The overexpression of 14-3-3 sigma significantly suppressed the proliferation of H520 cells in vitro and in vivo. CONCLUSION: The inactivation of 14-3-3 sigma may be a very early event in tumorigenesis and could facilitate the initiation and progression of lung SqCC in a sustainable way. PMID- 26557910 TI - Bronchoscopic debulking for endobronchial malignancy: Predictors of recanalization and recurrence. AB - BACKGROUND: Central airway obstruction related to endobronchial malignancy is one of the most difficult oncological complications and requires efficient palliative intervention. METHODS: Fifty-three consecutive patients with unresectable endobronchial malignancy receiving bronchoscopic cryotherapy as palliative treatment were retrospectively reviewed. Efficiency was evaluated by the improvement of performance status (PS), and the best achievement of tumor removal was assessed as complete or partial removal. RESULT: Patients' PS after cryotherapeutic tumor removal improved from the baseline PS (P = 0.006). In multivariate logistic regression analysis, the compression part of the tumor (odds ratio [OR] 0.42; 95% confidence interval [CI] 0.23~0.75, P = 0.004) and the thin tumor stalk (OR 87.86; 95% CI 2.31~3337.37, P = 0.016) were independent predictors of complete tumor removal. Tumors larger than 9.3 cm, including compression and invasion parts, had the highest odds of being only partially removed (positive predictive value [PPV]: 88.2%, likelihood ratio [LR]+: 10.49); tumors smaller than 9.3 cm were likely to be completely removed (negative predictive value [NPV]: 80.6%, LR-: 0.34). After cryotherapy, re-obstruction was significantly associated with non-squamous cell carcinoma (65.7 vs. 16.7%, P = 0.001) and patients who had longer overall survival (11.7 vs. 1.5 months, P < 0.001). Odds of tumor re-obstruction increased 2.28-fold (PPV: 81.6%, LR+: 2.28) beyond two months; the odds decreased by 81% (NPV: 73.3%, LR-: 0.19) within two months. CONCLUSION: Debulking of a tumor using cryotherapy is a useful palliative treatment for endobronchial obstruction secondary to a variety of malignancies. PMID- 26557911 TI - Evolution of induction chemotherapy for non-small cell lung cancer over the last 30 years: A surgical appraisal. AB - BACKGROUND: Induction chemotherapy (ICT) is supposed to reduce the risk of micrometastatic progression and improve resectability of non-small cell lung cancer (NSCLC). However, best indications for ICT strategy remain unclear in published meta-analyses. Based on this observation, an evaluation of daily practice is of importance. Therefore, we reviewed indications and efficacy time trends in our 30-year series. METHODS: A database including all patients with NSCLC who underwent surgical resection in two French centers from 1980 to 2009 (n = 5563) was prospectively set and retrospectively reviewed. The indications, clinical and pathologic response rates, and overall survival of ICT patients (n = 732) were analyzed during three successive time-periods: P1 from 1980 to 1989, P2 from 1990 to 1999, and P3 from 2000 to 2009. RESULTS: The proportion of patients who benefited from ICT increased over time, from 2.8% (n = 35) in P1 to 12.5% (n = 274) in P2, and 20.2% (n = 423) in P3. Indications evolved over time with more N2 patients (n = 211; 49.8%) and less initially unresectable patients (n = 72; 17%) in P3. The clinical response rate between P1 and P2 increased. Five and 10 year survival rates of ICT patients were 35.2% and 21.5%, respectively. In multivariate analysis, time-period, age, type of resection, histology, and pathologic response to chemotherapy were significant prognostic factors. CONCLUSIONS: Our report on the off-trial use of induction therapy during the last 30 years demonstrates an increased use of ICT, a progressive focus on N2 disease, and improved response rates. PMID- 26557912 TI - DNA repair gene ERCC1 C118T polymorphism predicts sensitivity of recurrent esophageal cancer to radiochemotherapy in a Chinese population. AB - BACKGROUND: DNA repair gene polymorphisms could alter DNA repair capacity and therefore associate with tumor sensitivity to radiochemotherapy. This study assessed excision repair cross-complementing group 1 (ERCC1) C118T and X-ray cross-complementing group 1 (XRCC1) G399A single-nucleotide polymorphisms in esophageal patients for an association with sensitivity to radiation and chemotherapy. METHODS: Esophageal squamous cell carcinoma patients (n = 118) who relapsed after surgery were enrolled for assessment of ERCC1 C118T and XRCC1 G399A polymorphisms by direct DNA sequencing. RESULTS: The response rate of treatments was 48.30%: 14 complete response (CR, 11.86%), 43 partial response (PR, 36.44%), 49 stable disease (SD, 41.53%), and 12 progressive disease (PD, 10.17%). ERCC1 C118T was significantly associated with treatment response (C/T vs. C/C + T/T, odds ratio [OR] = 6.035, 95% confidence interval [CI]: 2.114 17.226, P = 0.001) after adjusting for other clinicopathological factors. Patients carrying the C/T genotype had significantly prolonged overall survival (OS) compared with C/C and T/T (median OS 43.00 vs. 27.00, P = 0.027). Multivariate Cox regression showed that a response was only an independent prognostic factor for OS (CR + PR vs. SD+PD, HR = 0.471 95% CI 0.269-0.826, P = 0.009). Grade III and IV adverse events occurred in 12 of 118 patients (10.17%). Only concurrent radiochemotherapy significantly increased these adverse events (OR = 26.529, 95% CI 2.312-304.389, P = 0.008). CONCLUSION: ERCC1 C118T could be a predictive factor for the response to radiotherapy and chemotherapy, but not a prognostic factor for OS in esophageal cancer patients after surgery. PMID- 26557913 TI - Loss of heterozygosity at the human leukocyte antigen locus in thymic epithelial tumors. AB - BACKGROUND: To study the relationship between loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus and the pathogenicity and clinicopathological features of thymic epithelial tumors (TET). METHODS: Tumor and adjacent normal tissues were isolated from 36 TET patients. Five microsatellite loci (D6S1666, D6S265, D6S273, DS6276, and D6S291) within the HLA locus were amplified by polymerase chain reaction. DNA sequencing was used to measure the frequency of microsatellite LOH. RESULTS: LOH was identified in at least one locus in 83.6% of TET patients. LOH frequency at D6S1666, D6S265, D6S273, D6S276, and D6S291 was 44.4%, 16.7%, 30.5%, 38.9%, and 36.1% respectively. There was no significant association between LOH frequency in TET with tumor severity, or in the presence or absence of myasthenia gravis. CONCLUSIONS: D6S1666, D6S265, D6S273, DS6S276, and D6S29 are sensitive loci for studying microsatellite LOH in TET. LOH within the HLA complex is implicated in the occurrence and development of TET, with the HLA-DQA1 gene likely involved. However, an understanding of the relationship between LOH and the clinicopathological features of TET requires a larger sample size than that of the present study. PMID- 26557915 TI - Radiofrequency ablation (RFA) for palliative treatment of painful non-small cell lung cancer (NSCLC) rib metastasis: Experience in 12 patients. AB - BACKGROUND: Painful rib metastasis is common in non-small cell lung cancer (NSCLC). Pain is often partially or totally refractory to analgesic medications or the side effects of medication are unacceptable. We report the safety and efficacy of a new method: radiofrequency ablation (RFA) in treating painful NSCLC rib metastasis. METHODS: RFA procedures were completed in 12 patients with painful rib metastasis. Patient age ranged from 66-83 years (mean 74.8 years, standard deviation (SD) = 5.3). There were four cases of squamous-carcinoma, seven adenocarcinomas, and one case of large cell carcinoma. Pain caused by neoplasm size, pain levels pre-procedure and post-procedure (as assessed using the visual analog scale, VAS), time length, and target temperature of RFA treatments were documented. RESULTS: RFA procedures were performed with 100% technical success. The mean pre-procedure and post-procedure pain, as measured by the VAS, was 7.9 (SD = 0.90) and 3.4 (SD = 0.99), respectively. No symptomatic complications occurred. Non-symptomatic complications included one case of pneumothorax and one case of hemoptysis. CONCLUSION: RFA appears to be a safe, practical, and effective method for the palliative treatment of painful NSCLC chest wall metastasis. PMID- 26557914 TI - Expression of calcium sensing receptor and E-cadherin correlated with survival of lung adenocarcinoma. AB - BACKGROUND: It has been reported that the calcium sensing receptor (CaSR), a widely expressed G protein-coupled receptor, can stimulate cell differentiation and proliferation. However, in malignant tumors, loss of CaSR expression has been associated with tumorigenesis, metastasis, and progression. Recent studies have indicated that the CaSR could promote the expression of E-cadherin, which was considered a tumor suppressor. However, in human lung adenocarcinoma, the importance of the CaSR and E-cadherin has not been sufficiently investigated. METHODS: Expression levels of CaSR and E-cadherin in paraffin sections from 117 resected lung adenocarcinoma patients were evaluated by immunohistochemistry. We analyzed the correlation between our target proteins and clinical variables. Clinical significance was analyzed by multivariate Cox regression analysis, Kaplan-Meier curve, and log-rank test. RESULTS: Expression of the CaSR in lung adenocarcinoma tissue was significantly lower than in the normal sample (P = 0.003). Kendall tau-b analysis showed that, in a lung adenocarcinoma sample, the expression of CaSR positively correlated with a high level of E-cadherin (P < 0.001). Lung adenocarcinoma patients with a strong expression of CaSR (P = 0.034) or E-cadherin (P = 0.001) had longer overall survival. Multivariate Cox proportional hazards model analysis showed that the combined marker was an independent prognostic indicator of overall survival (hazard ratio = 0.440, confidence interval = 0.249-0.779, P = 0.005). CONCLUSIONS: We identified the CaSR as a new prognostic biomarker in lung adenocarcinoma. These results also suggested that the CaSR may become a new therapeutic target of lung adenocarcinoma. PMID- 26557916 TI - Prognostic significance of the pN classification supplemented by body mass index for esophageal squamous cell carcinoma. AB - BACKGROUND: Body mass index (BMI) has been associated with the risk of esophageal cancer. But the influence of BMI on postoperative complications and prognosis has always been controversial. METHODS: Between 2000 and 2007, 424 patients with esophageal squamous cell carcinoma (ESCC) underwent R0 esophagectomy at our center without neoadjuvant therapy. We performed univariate and multivariate analyses to identify prognostic factors for survival. RESULTS: Patients were divided into three groups according to Asian-specific BMI cut-off value: underweight (n = 45), normal weight (n = 228), and overweight and obese (n = 151). Mean follow-up time was 39 months. The five-year overall survival (OS) rate was 19%, 34%, and 42% for underweight, normal weight, and overweight and obese, respectively (P < 0.001). The five-year disease-free survival (DFS) rate was 24%, 41%, and 74% for underweight, normal weight, and overweight and obese, respectively (P < 0.001). Multivariate analysis showed that pT, pN, and BMI were independent prognostic factors for DFS and OS. The C-index to the combined model showed improved predictive ability when compared to the pN classification (0.779 vs. 0.734). CONCLUSION: Preoperative BMI was an independent prognostic factor for OS and DFS. The proposed new prognostic model with the pN classification supplemented by BMI might improve the ability to discriminate ESCC patients' outcome. PMID- 26557917 TI - Efficacy and safety of chemotherapy for newly diagnosed advanced non-small cell lung cancer with venous thromboembolism. AB - BACKGROUND: Venous thromboembolism (VTE) is a serious complication in patients with lung cancer. The benefit of chemotherapy for lung cancer patients with VTE remains unknown. This study was conducted to elucidate the efficacy and safety of chemotherapy for advanced non-small cell lung cancer (NSCLC) in patients with VTE. METHODS: Newly diagnosed patients with advanced (i.e. stage IIIB and IV) NSCLC with VTE who received systemic chemotherapy were studied. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were retrospectively analyzed. RESULTS: In this study, 21 patients who received chemotherapy plus anticoagulation therapy between December 2009 and February 2011 were included. The objective response and disease control rates within the first regimen were 14.29% (3/21) and 76.19 %(16/21), respectively. The median PFS, one year survival rate, and median OS were 5.50 months, 33.30%, and 8.70 months, respectively. The main grade 3/4 toxicities observed included neutropenia (28.57%), nausea 4 (19.05%), and anemia 2 (9.52%). Major bleeding was not observed. CONCLUSION: Chemotherapy for newly diagnosed patients with advanced NSCLC and VTE was feasible and had acceptable toxicity; however, the survival of these patients remained inferior to that of patients without VTE. PMID- 26557918 TI - Micro ribonucleic acid (RNA)-101 inhibits cell proliferation and invasion of lung cancer by regulating cyclooxygenase-2. AB - BACKGROUND: Micro ribonucleic acid (miR-101) can regulate the expression of cyclooxygenase-2 (COX-2) and participate in the pathogenesis of malignant tumors. This study investigates the effects of miRNA-101 and COX-2 in lung cancer and the impact of miR-101 on the proliferation and invasion of human lung cancer A549 cell line. METHODS: The expression of miR-101 in 20 separate lung cancer tissues was detected by real time polymerase chain reaction; COX-2 expression was also detected. A549 cells were transfected with miR-101 or negative control oligonucleotide duplex mimic (miR-NC). In vivo tumorigenesis abilities were detected in localized human lung cancer xeno-transplant models in BALB/c nude mice. RESULTS: MiR-101 expression was significantly lower and the level of COX-2 significantly higher in lung cancer tissues than in adjacent parenchyma (2.918 +/ 1.006 vs. 5.953 +/- 1.976, P = 0.001; 0.887 +/- 0.260 vs. 0.355 +/- 0.156, P = 0.001, respectively). Correlation analysis revealed that miR-101 negatively correlated with COX-2 in lung cancer tissues (R = -0.596, P = 0.002). Compared with A549-miR-NC cells, the expression of COX-2 was significantly decreased in A549 cells transfected with miR-101 (P < 0.001). The proliferation of A549 cells was markedly inhibited after transfection of miR-101. The in vivo tumor growth of A549 cells transfected with miR-101 was significantly slower than wide type A549 cells. CONCLUSION: MiR-101 expression is decreased in lung cancer, inducing an increase in COX-2 level. Enforced expression of miR-101 can remarkably reduce the cell proliferation and invasion ability of lung cancer cells. PMID- 26557919 TI - Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer: A multicenter randomized controlled clinical trial. AB - BACKGROUND: This study evaluated the efficacy and safety of irinotecan/cisplatin (IP) and etoposide/cisplatin (EP) in extensive-stage small cell lung cancer (ES SCLC) and the distribution of uridine diphosphate glucuronosyltransferase (UGT1A1). The relationship between UGT1A1 genotypes and patient outcomes was also assessed. METHOD: Patients with untreated ES-SCLC were randomly assigned to receive either IP or EP, and blood specimens were collected to test the genotypes of UGT1A1*28 and UGT1A1*6. The association of efficacy and toxicity of an IP regimen with UGT1A1 genotype was analyzed. RESULTS: Of the 62 patients enrolled from three institutions, 30 patients were in the IP and 32 patients were in the EP arms, respectively. Disease control rates with IP and EP were 83.3% and 71.9%, respectively (P = 0.043). Median progression-free survival for IP and EP were both six months. Median overall survival for IP and EP were 18.1 and 15.8 months respectively, without significant difference. Grade 3-4 thrombocytopenia was more common with EP (18.8% vs. 6.7%; P = 0.035), while the incidence of diarrhea was higher with IP (70% vs. 15.6%; P = 0.008). The incidence of grade 1-4 late-onset diarrhea of wild-type, heterozygous, and homozygous UGT1A1*28 were 65.0%, 85.7%, and 66.7%, respectively (P = 0.037). UGT1A1*28 polymorphisms, Eastern Cooperative Oncology Group performance status, and chemotherapy cycles were essential factors affecting grade 1-4 late-onset diarrhea in logistic regression analysis. CONCLUSIONS: The efficacy of the IP regimen was similar to the EP regimen for untreated ES-SCLC. UGT1A1 polymorphisms were associated with late-onset diarrhea; however, there was no influence on efficacy. PMID- 26557920 TI - Expression of Pax8 is decreased and bortezomib does not increase the iodine uptake in thyroid carcinoma cells. AB - Fundamental treatment for papillary thyroid carcinoma (PTC) involves total or subtotal thyroidectomy. Iodine-131 ((131)I) is routinely utilized to target remnant thyroid cancer and metastasis after thyroidectomy. The effectiveness of other therapeutic modalities remains unsatisfactory; thus, these patients have a poor prognosis. The manner in which the ability of (131)I uptake can be improved is vital for their prognosis. Bortezomib has been used as a re-differentiation agent for the treatment of patients with multiple myeloma; however, little is reported about the role of bortezomib in thyroid cancer. To evaluate the therapeutic potential of bortezomib in a human PTC cell line, expression of paired-box 8 (Pax8) protein was determined using Western blot in PTC, normal thyroid, and anaplastic/undifferentiated thyroid carcinoma (ATC) cells. The expression of Pax8 protein in PTC cells pretreated with bortezomib was determined using the same method. Iodine uptake was determined using (131)I radioactivity assay. The level of Pax8 protein in normal thyroid cells was significantly higher than in PTC (P < 0.05) and ATC cells (P < 0.05); its expression in PTC cells was also significantly higher than in ATC cells (P < 0.05). The PTC cells in the bortezomib-treated group showed a higher expression of Pax8 protein than the control group (P < 0.05). These findings indicate that bortezomib can increase the expression of Pax8, but does not significantly increase the iodine uptake of PTC cells. PMID- 26557921 TI - Pulmonary artery sarcoma: a rare thoracic tumor frequently misdiagnosed at presentation. AB - This case illustrates a rare but important differential diagnosis of pulmonary emboli in the field of thoracic oncology, that of pulmonary artery sarcoma. It describes particular clinical features that may raise suspicion of this tumor in cases of suspected pulmonary emboli, and highlights novel radiological modalities and tissue sampling techniques in such cases. Surgical resection, as part of multi-modality therapy, is the cornerstone of treatment that has seen survival dramatically improve in recent years for patients with this rare cancer. PMID- 26557922 TI - Histological transformation from non-small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor. AB - Several cases of acquired resistance in patients with activating epidermal growth factor receptor (EGFR) mutation have been reported. However, rare clinical cases exist of a transformation to small cell lung cancer (SCLC) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). We report a case of non-small cell lung cancer (NSCLC) with L858R mutation at the time of diagnosis. After failure of EGFR-TKI therapy, we performed additional histopathologic examinations. We confirmed that the patient had a histological transformation from NSCLC to SCLC. We performed chemotherapy with etoposide and cisplatin against the SCLC and radiologic findings were improved. PMID- 26557924 TI - Giant mediastinal thymolipoma in a patient with Gardner's syndrome. AB - Gardner's syndrome is a hereditary disorder inherited as an autosomal dominant with high penetrance and variable expression that is caused by a mutation of the adenomatous polyposis coli gene. It is characterized by gastrointestinal polyps associated with multiple osteomas, dental anomalies, and skin and soft tissue tumors. We present a case of 30-year-old female patient with Gardner's syndrome who presented with a giant mediastinal thymolipoma. The tumor was completely excised through a bilateral posterolateral thoracotomy. There was no recurrence after 20 months of follow-up. We therefore suggest that physicians who regularly treat patients with Gardner's syndrome carefully examine for thoracic manifestations. PMID- 26557923 TI - Spontaneous regression of non-small cell lung cancer that progressed after multiple chemotherapies: A case report. AB - Spontaneous regression (SR) of cancer is defined as a complete or partial, temporary or permanent disappearance of all or at least some relevant parameters of malignant disease with inadequate or no treatment. SR of cancer is an extremely rare phenomenon. We report a case of a 67-year-old man who experienced SR of non-small-cell lung cancer (NSCLC), which progressed after fifth-line chemotherapy and regressed after chemotherapy ceased. Surprisingly, the primary tumor size continued to decrease for more than 13 months and his general condition markedly improved after discontinuation of the chemotherapy. To our knowledge, this is the first report of SR in a patient with NSCLC that was not responsive to a fifth round of chemotherapy. PMID- 26557926 TI - Survey on granularity clustering. AB - With the rapid development of uncertain artificial intelligent and the arrival of big data era, conventional clustering analysis and granular computing fail to satisfy the requirements of intelligent information processing in this new case. There is the essential relationship between granular computing and clustering analysis, so some researchers try to combine granular computing with clustering analysis. In the idea of granularity, the researchers expand the researches in clustering analysis and look for the best clustering results with the help of the basic theories and methods of granular computing. Granularity clustering method which is proposed and studied has attracted more and more attention. This paper firstly summarizes the background of granularity clustering and the intrinsic connection between granular computing and clustering analysis, and then mainly reviews the research status and various methods of granularity clustering. Finally, we analyze existing problem and propose further research. PMID- 26557925 TI - China national lung cancer screening guideline with low-dose computed tomography (2015 version). AB - BACKGROUND: Lung cancer is the leading cause of cancer-related death in China. Results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. METHODS: A China national lung cancer screening guideline was developed by lung cancer early detection and treatment expert group appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. RESULTS: Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. CONCLUSIONS: A lung cancer screening guideline is provided for the high-risk population in China. PMID- 26557927 TI - Dynamical analysis of periodic bursting in piece-wise linear planar neuron model. AB - A piece-wise linear planar neuron model, namely, two-dimensional McKean model with periodic drive is investigated in this paper. Periodical bursting phenomenon can be observed in the numerical simulations. By assuming the formal solutions associated with different intervals of this non-autonomous system and introducing the generalized Jacobian matrix at the non-smooth boundaries, the bifurcation mechanism for the bursting solution induced by the slowly varying periodic drive is presented. It is shown that, the discontinuous Hopf bifurcation occurring at the non-smooth boundaries, i.e., the bifurcation taking place at the thresholds of the stimulation, leads the alternation between the rest state and spiking state. That is, different oscillation modes of this non-autonomous system convert periodically due to the non-smoothness of the vector field and the slow variation of the periodic drive as well. PMID- 26557928 TI - Cortical activities of heat-sensitization responses in suspended moxibustion: an EEG source analysis with sLORETA. AB - Moxibustion is under active research as a complementary and alternative treatment for various diseases such as pain. "Heat-sensitization" responses have been reported during suspended moxibustion, whose occurrence is associated with significantly better therapeutic effects. The present study aimed to investigate the cortical activities of this interesting phenomenon by a standardized low resolution brain electromagnetic tomography. We performed electroencephalography recording in a group of patients with chronic low back pain before, during, and after moxibustion treatment at Yaoyangguan (DU3) areas. 11 out of 21 subjects experienced strong heat-sensitization during moxibustion, which were accompanied with significant decreases of current densities in the beta frequency bands in prefrontal, primary and second somatosensory, and cingulate cortices, as well as increased current densities in the alpha2 band in the left insula. No changes were detected in patients without sensitization responses, or in the post moxibustion phase of either group. These data indicated widespread activity changes across different frequency bands during heat-sensitization. Cortical oscillatory activities could be used to evaluate the "heat-sensitization" responses during suspended moxibustion. PMID- 26557929 TI - Single-trial detection for intraoperative somatosensory evoked potentials monitoring. AB - Abnormalities of somatosensory evoked potentials (SEPs) provide effective evidence for impairment of the somatosensory system, so that SEPs have been widely used in both clinical diagnosis and intraoperative neurophysiological monitoring. However, due to their low signal-to-noise ratio (SNR), SEPs are generally measured using ensemble averaging across hundreds of trials, thus unavoidably producing a tardiness of SEPs to the potential damages caused by surgical maneuvers and a loss of dynamical information of cortical processing related to somatosensory inputs. Here, we aimed to enhance the SNR of single trial SEPs using Kalman filtering and time-frequency multiple linear regression (TF-MLR) and measure their single-trial parameters, both in the time domain and in the time-frequency domain. We first showed that, Kalman filtering and TF-MLR can effectively capture the single-trial SEP responses and provide accurate estimates of single-trial SEP parameters in the time domain and time-frequency domain, respectively. Furthermore, we identified significant correlations between the stimulus intensity and a set of indicative single-trial SEP parameters, including the correlation coefficient (between each single-trial SEPs and their average), P37 amplitude, N45 amplitude, P37-N45 amplitude, and phase value (at the zero-crossing points between P37 and N45). Finally, based on each indicative single-trial SEP parameter, we investigated the minimum number of trials required on a single-trial basis to suggest the existence of SEP responses, thus providing important information for fast SEP extraction in intraoperative monitoring. PMID- 26557930 TI - Function projective synchronization of memristor-based Cohen-Grossberg neural networks with time-varying delays. AB - This paper deals with the problem of function projective synchronization for a class of memristor-based Cohen-Grossberg neural networks with time-varying delays. Based on the theory of differential equations with discontinuous right hand side, some novel criteria are obtained to realize the function projective synchronization of addressed networks by combining open loop control and linear feedback control. As some special cases, several control strategies are given to ensure the realization of complete synchronization, anti-synchronization and the stabilization of the considered memristor-based Cohen-Grossberg neural network. Finally, a numerical example and its simulations are provided to demonstrate the effectiveness of the obtained results. PMID- 26557932 TI - Integrating new data balancing technique with committee networks for imbalanced data: GRSOM approach. AB - To deal with imbalanced data in a classification problem, this paper proposes a data balancing technique to be used in conjunction with a committee network. The proposed data balancing technique is based on the concept of the growing ring self-organizing map (GRSOM) which is an unsupervised learning algorithm. GRSOM balances the data through growing new data on a well-defined ring structure, which is iteratively developed based on the winning node nearby the samples. Accordingly, the new balanced data still preserve the topology of the original data. The performance of our proposed method is evaluated using four real data sets from the UCI Machine Learning Repository and the classification performance is measured using the fivefold cross validation method. Classifiers with most common data balancing techniques, namely the Minority Over-Sampling Technique (SMOTE) and the Random under-sampling Technique (RT), are used as the baseline methods in this study. The results reveal that a committee of classifiers constructed using GRSOM performs at least as well as the baseline methods. The results also suggest that classifiers constructed using neural networks with the backpropagation algorithm are more robust than those using the support vector machine. PMID- 26557931 TI - A cerebral blood flow evaluation during cognitive tasks following a cervical spinal cord injury: a case study using transcranial Doppler recordings. AB - A spinal cord injury (SCI) is one of the most common neurological disorders. In this paper, we examined the consequences of upper SCI in a male participant on the cerebral blood flow velocity. In particular, transcranial Doppler was used to study these effects through middle cerebral arteries (MCA) during resting-state periods and during cognitive challenges (non-verbal word-generation tasks and geometric-rotation tasks). Signal characteristics were analyzed from raw signals and envelope signals (maximum velocity) in the time domain, the frequency domain and the time-frequency domain. The frequency features highlighted an increase of the peak frequency in L-MCA and R-MCA raw signals, which revealed stronger cerebral blood flow during geometric/verbal processes respectively. This underlined a slight dominance of the right hemisphere during word-generation periods and a slight dominance of the left hemisphere during geometric processes. This finding was confirmed by cross-correlation in the time domain and by the entropy rate in information-theoretic domain. A comparison of our results to other neurological disorders (Alzheimer's disease, Parkinson's disease, autism, epilepsy, traumatic brain injury) showed that the SCI had similar effects such as general decreased cerebral blood flow and similar regular hemispheric dominance in a few cases. PMID- 26557933 TI - Event-related potentials elicited by social commerce and electronic-commerce reviews. AB - There is an increasing interest regarding the use of electroencephalography (EEG) in social commerce and electronic commerce (e-commerce) research. There are several reviews in the field of social commerce or e-commerce; these have great potential value and mining them is fundamental and significant. To our knowledge, EEG is rarely applied to study these. In this study, we examined the neural correlates of social commerce reviews (SCRs) and e-commerce reviews (ECRs) by using them as stimuli to evoke event-related potentials. All SCRs were from friends through a social media platform, whereas ECRs were from strangers through an e-commerce platform. The experimental design was similar to that of a priming paradigm, and included 40 pairs of stimuli consisting of product information (prime stimulus) and reviews (target stimulus). The results showed that the P300 component was successfully evoked by SCR and ECR stimuli. Moreover, the P300 components elicited by SCRs had higher amplitudes than those elicited by ECRs. These findings indicate that participants paid more attention to SCRs than to ECRs. In addition, the associations between neural responses and reviews in social commerce have the potential to assist companies in studying consumer behaviors, thus permitting them to enhance their social commerce strategies. PMID- 26557934 TI - New pharmaceuticals in inflammatory bowel disease. AB - This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment. PMID- 26557935 TI - Cytokeratins in gastroenterology. Systematic review. AB - Keratins are proteins that form intermediate filaments of epithelial cell cytoskeleton. The utility of keratin expression determination is based on the fact that epithelial cells acquire a specific pattern of keratin expression during differentiation and maturation, which reflects the specificity of the tissue and the degree of maturation, and generally remains stable during carcinogenesis. Determination of the pattern makes it possible to identify the origin of cells in diagnosing neoplastic lesions as well as in research on pathophysiology or the possibility to apply keratin-positive cell detection in the process of cancer staging and treatment planning. As keratins undergo degradation during apoptosis as caspase substrate the identification of the caspase-derived K18 fragment by the use of specific monoclonal antibody allows us to estimate the apoptosis/necrosis ratio, especially in liver pathology, e.g. nonalcoholic steatohepatitis, chronic hepatitis or graft-versus-host disease or in assessing response to antiviral or antitumour therapy. PMID- 26557936 TI - Enteral feeding and its impact on the gut immune system and intestinal mucosal barrier. AB - Enteral feeding is the preferred method of nutritional therapy. Mucosal lack of contact with nutrients leads do lymphoid tissue atrophy, immune system functional decline, and intensification in bacterial translocation. Currently, it is assumed that microbiome is one of the body organs that has a significant impact on health. The composition of microbiome is not affected by age, sex, or place of residence, although it changes rapidly after diet modification. The composition of the microbiome is determined by enterotype, which is specific for each organism. It has a significant impact on the risk of diabetes, cancer, atherosclerosis, and other diseases. This review gathers data on interaction between gut-associated lymphoid tissue, mucosa-associated lymphoid tissue, microbiome, and the intestinal mucosal barrier. Usually, the information on the aforementioned is scattered in specialist-subject magazines such as gastroenterology, microbiology, genetics, biochemistry, and others. PMID- 26557937 TI - Haemophagocytic lymphohistiocytosis in inflammatory bowel disease with virus infection. AB - Patients with inflammatory bowel disease (IBD) are at risk of developing haemophagocytic lymphohistiocytosis (HLH) because of chronic systemic inflammation as well as exposure to immunosuppressive medications. The two main causes of HLH in IBD patients are infection with cytomegalovirus and Epstein-Barr virus. Patients with Crohn's disease are more susceptible to HLH than those with ulcerative colitis. The majority of cases are seen in people receiving an immunosuppressive regimen that included thiopurines. PMID- 26557938 TI - Current management of anal fistulas in Crohn's disease. AB - Anal fistulas occurring in Crohn's disease (CD) comprise a risk factor of severe course of inflammation. They are frequently intractable due to various factors such as penetration of the anal canal or rectal wall, impaired wound healing, and immunosuppression, among others. Anal fistulas typical to CD develop from fissures or ulcers of the anal canal or rectum. Accurate identification of the type of fistula, such as low and simple or high and complex, is crucial for prognosis as well as for the choice of treatment. If fistulotomy remains the gold standard in the surgical treatment of the former, it is contraindicated in high and complex fistulas due to possible risk of damage to the anal sphincter with subsequent faecal incontinence. Therefore, the latter require a conservative and palliative approach, such as an incision and drainage of abscesses accompanying fistulas or prolonged non-cutting seton placement. Currently, conservative, sphincter-preserving, and definitive procedures such as mucosal advancement or dermal island flaps, the use of plugs or glue, video assisted anal fistula treatment, ligation of the intersphincteric track, and vacuum assisted closure are gaining a great deal of interest. Attempting to close the internal opening without injuring the sphincter is a major advantage of those methods. However, both the palliative and the definitive procedures require adjuvant therapy with medical measures. PMID- 26557939 TI - Evaluation of familial aggregation, vegetable consumption, legumes consumption, and physical activity on functional constipation in families of children with functional constipation versus children without constipation. AB - INTRODUCTION: Constipation is a frequent complication in paediatrics. Most of the constipation is functional. Functional constipation constitutes 25% of visits in paediatric gastroenterology clinics. Two studies were published regarding aggregation or clustering of functional constipation. Only one of these research projects was about a paediatric population. AIM: To elucidate the cluster pattern of constipation among the families of children with constipation. MATERIAL AND METHODS: This case-control study was carried out on the families of 37 children < 18 years old with chronic functional constipation and the families of 37 healthy children as controls. Cases were enrolled in the study according to Rome III criteria for constipation. The control group was selected from children < 18 years old who visited the well baby clinic of the university. Parents and siblings were evaluated regarding constipation. Rome II and III were used for evaluation of constipation for adults and children, respectively. Data was analysed using SPSS (Chicago, IL, USA). The chi(2) and t-test were used for comparison. RESULTS: Physical activity and vegetable consumption were seen more frequently in the control group compared to the cases, but these differences were statistically insignificant. Constipation in mothers was significantly higher in the case group compared to the control group (p = 0.015). There was no significant difference between the two groups regarding exercise and vegetable consumption. CONCLUSIONS: The frequency of constipation among mothers was significantly higher in the case group compared to the control group. Another study is recommended in a larger population for evaluation of genetic background, diet, physical activity, and familial clustering among mothers of children with constipation. PMID- 26557940 TI - Comparing the efficacy of four different protocols for eradicating of Helicobacter pylori infection in Ahvaz, southwest Iran. AB - INTRODUCTION: Helicobacter pylori (H. pylori) is the common cause of many gastrointestinal diseases, especially peptic ulcer. Therefore, a successful treatment of this infection decreases the financial burden on health systems. AIM: Different combinations of antibiotics are used for the eradication of this bacterium worldwide. The goal of this study is to compare the efficacy of four different protocols used for this purpose in Ahvaz. MATERIAL AND METHODS: A total number of 400 patients with H. pylori infection were randomly divided into four groups (100 in each): (1) OAC: omeprazole (20 mg/b.i.d.), amoxicillin (1000 mg/b.i.d.), clarithromycin (500 mg/b.i.d.) for 10 days. (2) OCF: omeprazole (20 mg/b.i.d.), ciprofloxacin (500 mg/b.i.d.), furazolidone (100 mg/b.i.d.) for 10 days. (3) OBAM: omeprazole (20 mg/b.i.d.), bismuth subcitrate (240 mg/b.i.d.), amoxicillin (1000 mg/b.i.d.), metronidazol (500 mg/b.i.d.) for 14 days. (4) OBTM: omeprazole (20 mg/b.i.d.), bismuth subcitrate (240 mg/b.i.d.), tetracycline (500 mg/b.i.d.), metronidazol (500 mg/b.i.d.) for 14 days. At the end the viability of the bacterium was assessed by C(14) urea breath test. RESULTS: The rate of H. pylori eradication was 92%, 59%, 73%, and 76% in OAC, OCF, OBAM, and OBTM groups, respectively (based on intention to treat analysis). The eradication rate was 93.9%, 62.1%, 77.7%, and 84.4% in OAC, OCF, OBAM, and OBTM groups, respectively (based on per protocol analysis). There was a statistically significant increase in eradication rate in the OAC group in comparison with the others (p < 0.001). CONCLUSIONS: Standard triple therapy (omeprazole, amoxicillin, clarithromycin) remains the most effective regimen for H. pylori eradication in Ahvaz. PMID- 26557941 TI - Leisure time physical activity and health-related behaviours after liver transplantation: a prospective, single-centre study. AB - INTRODUCTION: Leisure time physical activity is of proven significance in surveys of fitness levels in various patient groups. Low physical functioning may affect recovery after liver transplantation (LTx). AIM: To assess patients' leisure time activity and health-related habits after transplantation. MATERIAL AND METHODS: One hundred and seven patients after LTx were included. They were divided into groups depending on aetiology of liver problem and the period after LTx. Minnesota Leisure Time Physical Activity Questionnaire (MILTPAQ) and Health Behaviour Inventory (HBI) were applied. RESULTS: Neither the primary indication for the procedure nor the period after surgery had a significant relationship with physical activity assessed with MILTPAQ; however, activity was lower in females than males (1804.3 +/-1848.9 vs. 2619.9 +/-2067; p = 0.03). Age at survey/surgery was inversely associated with higher activity (p = 0.02 and p = 0.03, respectively). Health Behaviour Inventory analysis showed a correlation between all four of its domains and age at transplantation/survey (p < 0.001 for both). There was a negative correlation between positive mental attitude and body mass index (BMI). CONCLUSIONS: The primary indications for grafting and, surprisingly, the period after surgery did not seem to be related to the patients' physical activity in leisure time. Younger and leaner patients appeared to understand the standards of healthy behaviour better and implement them in their daily activities. As higher BMI are associated with a negative mental attitude in patients after LTx, a particular emphasis should be placed on proper counselling in this subgroup of patients. PMID- 26557942 TI - Rectal prolapse in children: a study of 71 cases. AB - INTRODUCTION: Prolapse of the rectum is the herniation of the rectum through the anus, which may be categorised as mucosal or complete. AIM: To evaluate the clinical manifestation, treatment, and surgical complications of children with rectal prolapse over a 6-year period. MATERIAL AND METHODS: This study was carried out on children aged < 14 years who were admitted or referred for rectal prolapse that failed to respond after medical treatment in Imam Khomeini and Abouzar Children's Hospital. Duration of the study was 6 years starting in March 2002. These cases were referred after failure of medical and conservative treatment. Age, sex, clinical manifestation, and type of procedure were recorded. Analysis was done using SPSS version 11.0 (SPSS Inc, Chicago, IL, USA). The chi(2) test was used for comparison. RESULTS: Seventy-one cases were included in this study. Of these cases, 50 (70.4%) were male and 21 (29.6%) were female (p < 0.0001). Mean age of cases was 4.97 +/-3.42 years (range: 2 days to 13 years). Of the male cases, 38% were in the age range of 3-6 years. In female cases, 57.1% were in the range of 1.5-3 years. Of all 71 cases, injection sclerotherapy was done for 50 (70.43%) for the first time. Twenty-one cases had history of injection sclerotherapy and 16 (22.53%) were treated by perineal surgery, and 5 (7.04%) had abdominal surgery. One case experienced recurrent rectal prolapse (1.40%) following injection sclerotherapy. CONCLUSIONS: In girls, more than half of the cases were in the age range 1.5-3 years. Among male cases, 38% were in the age range of 1.5-3 years. The results of treatment of rectal prolapse in our hospitals was similar to that seen in developed countries. PMID- 26557943 TI - Diabetes mellitus and the risk of cholangiocarcinoma: an updated meta-analysis. AB - INTRODUCTION: A number of studies have shown that diabetes mellitus is implicated in susceptibility to several cancers. However, the relationship between diabetes and cholangiocarcinoma remain unclear. AIM: To quantitatively assess the relationship between diabetes and incidence of cholangiocarcinoma in cohort and case-control studies. MATERIAL AND METHODS: A literature search was performed for entries from 1996 to 2014 using the PubMed and EMBASE databases. Studies were included if they reported odds ratios (OR) and corresponding 95% CI of cholangiocarcinoma with respect to diabetes mellitus. RESULTS: Twenty studies met the inclusion criteria, which included fifteen case-control studies and five cohort studies from Asia (n = 11), the United States (n = 5), and Europe (n = 4). Compared with individuals without diabetes, the pooled OR of cholangiocarcinoma was 1.74 (95% CI: 1.62-1.87, p = 0.568 for heterogeneity) for patients with diabetes, ICC (summary RR, 1.93; 95% CI: 1.65-2.25; p = 0.037 for heterogeneity), and ECC (summary RR, 1.66; 95% CI: 1.39-1.98; p = 0.001 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). CONCLUSIONS: The findings from this meta analysis suggest that diabetes may increase the risk of cholangiocarcinoma. This relationship needs to be confirmed by further follow-up studies. PMID- 26557944 TI - Mesenteric lymphadenitis caused by Yersinia enterocolitica. AB - Yersiniosis is an acute or chronic, zoonotic disease caused by infection of Gram negative rods Yersinia enterocolitica. It can be transmitted by the consumption of originally contaminated food products (pork, unpasteurized milk) or secondarily contaminated with animal or vegetable products. The clinical picture of infection may have a variable course is related to the age and physical condition of the patient, or pathogenic properties of microorganisms. Infection caused by Y. enterocolitica can occur in different clinical forms: food poisoning, colitis, mesentric lymphadenitis, erythema nodosum, arthritis, pharyngitis, pneumonia, meningitis, sepsis. The aim of this study was to present a rare case of infection with Y. enterocolitica mesenteric lymph nodes coexistent with appendicitis. PMID- 26557945 TI - Endoscopic removal of a battery that was lodged in the oesophagus of a two-year old boy for an extremely long time. AB - In the present work we describe a 2-year-old boy whose battery ingestion was overlooked, and who had the battery endoscopically removed from the upper part of his oesophagus after several months. This is the only described case of such a long impaction of a lithium battery in the oesophagus, without development of severe complications. We stress the necessity to take into account ingestion of a dangerous foreign body by children demonstrating unspecific clinical signs. PMID- 26557946 TI - Total Scalp Excision and Reconstruction Using a Free Omental Flap. PMID- 26557947 TI - Autografted Electrical Burn Complicated by Cutaneous Chromoblastomycosis. PMID- 26557948 TI - Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma. AB - Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis. PMID- 26557949 TI - Defining acute-on-chronic liver failure: East, West or Middle ground? AB - Acute-on-chronic liver failure (ACLF), a newly recognized clinical entity seen in hospitalized patients with chronic liver disease including cirrhosis, is associated with high short- and medium term morbidity and mortality. None of the definitions of ACLF proposed so far have been universally accepted, the two most commonly used being those proposed by the Asia-Pacific Association for the Study of Liver (APASL) and the European Association for the Study of Liver - Chronic Liver Failure (EASL-CLIF) consortium. On paper both definitions and diagnostic criteria appear to be different from each other, reflecting the differences in cut-off values for individual parameters used in diagnosis, the acute insult or precipitating event and the underlying chronic liver disease. Data directly comparing these two criteria are limited, and available studies reveal different outcomes when the two are applied to the same set of patients. However a review of the literature suggests that both definitions do not seem to identify the same set of patients. The definition given by the APASL consortium is easier to apply in day-to-day practice but the EASL-CLIF criteria appear to better predict mortality in ACLF. The World Gastroenterology Organization working party have proposed a working definition of ACLF which will identify patients from whom relevant data can be collected so that the similarities and the differences between the two regions, if any, can be clearly defined. PMID- 26557950 TI - Microwave ablation of hepatocellular carcinoma. AB - Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID- 26557951 TI - Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance. AB - The mechanism of action of ribavirin (RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus (HCV) infection are reviewed. RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper (Th) 1/2 cell balance to Th1 dominance. Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells, which contributes to differentiating naive Th cells into Th2 cells while reducing their interleukin-10 production. The effects on T-regulatory (Treg) cells were also investigated, and RBV inhibited the differentiation of naive Th cells into adaptive Treg cells by down-modulating forkhead box-P3. These findings indicate that RBV mainly down-regulates the activity of Th2 cells, resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes. Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications, regimens with RBV will be still be used because of their ability to facilitate the cellular immune response, which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV. PMID- 26557952 TI - Dietary supplements and pediatric non-alcoholic fatty liver disease: Present and the future. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. High prevalence of pediatric obesity and sedentary lifestyle has augmented the incidence of NAFLD in children. Obesity is associated with an increased risk of NAFLD through various mechanisms such as intensification of insulin resistance and increased levels of inflammatory markers. There is no approved medical intervention for treatment of pediatric NAFLD; the only proven strategy in management of pediatric NAFLD is lifestyle modification. Recently, the effects of nutritional supplements have been examined in the management of pediatric NAFLD. The purpose of this review is to summarize the studies evaluating the effects of nutritional supplements on pediatric NAFLD and explain the future direction in this field. PMID- 26557953 TI - Hepatocellular adenoma: An update. AB - Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions. PMID- 26557954 TI - Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease. AB - AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease (NAFLD) in patients with and without type 2 diabetes mellitus (T2DM) using updated nonalcoholic steatohepatitis clinical research network (NASH-CRN) grading system. METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2DM. This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author. The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison. The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist. The updated criteria for type 2 diabetes have been utilized for analysis. Background data of patients with NASH and NAFLD has been included. The mean differences were compared using chi(2) and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis. RESULTS: Patients with NAFLD and T2DM were significantly older (49.9 vs 43.0, P < 0.01), predominantly female (71.4 vs 56.3, P < 0.02), had higher rate of metabolic syndrome (88.7 vs 36.4, P < 0.01), had significantly higher aspartate transaminase (AST)/alanine transaminase (ALT) ratio (0.94 vs 0.78, P < 0.01) and Fib-4 index (1.65 vs 1.06, P < 0.01) as markers of NASH, showed higher mean NAFLD activity score (3.5 vs 3.0, P = 0.03) and higher mean fibrosis score (1.2 vs 0.52, P < 0.01) compared to patients with NAFLD without T2DM. Furthermore, advanced fibrosis (32.5 vs 12.0, P < 0.01) and ballooning (27.3 vs 13.3, P < 0.01) was significantly higher among patients with NAFLD and T2DM compared to patients with NAFLD without T2DM. On multivariate analysis, T2DM was independently associated with NASH (OR = 3.27, 95%CI: 1.43-7.50, P < 0.01) and advanced fibrosis (OR = 3.45, 95%CI: 1.53-7.77, P < 0.01) in all patients with NAFLD. There was a higher rate of T2DM (38.1 vs 19.4, P < 0.01) and cirrhosis (8.3 vs 0.0, P = 0.01) along with significantly higher mean Bilirubin (0.71 vs 0.56, P = 0.01) and AST (54.2 vs 38.3, P < 0.01) and ALT (78.7 vs 57.0, P = 0.01) level among patients with NASH when compared to patients with steatosis alone. The mean platelet count (247 vs 283, P < 0.01) and high-density lipoprotein cholesterol level (42.7 vs 48.1, P = 0.01) was lower among patients with NASH compared to patients with steatosis. CONCLUSION: Patients with NAFLD and T2DM tend to have more advanced stages of NAFLD, particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2DM. PMID- 26557955 TI - Human immunodeficiency virus and viral hepatitis among high-risk groups: Understanding the knowledge gap in the Middle East and North Africa Region. AB - AIM: To identify gaps in the existing knowledge on single, dual and triple infections of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in the Middle East and North Africa (MENA) region among men who have sex with men (MSMs), female sex workers (FSWs), injecting drug users (IDUs) and prisoners. METHODS: We performed an extensive literature search on articles published on the topic in the 25 countries of the MENA region. PubMed database was used as the main search engine. Case reports, case series, qualitative studies, editorials, commentaries, authors' replies and animal studies were excluded. Original articles and reviews dealing with the prevalence of HIV, HBV and HCV and their co-infection were included. Data on population type, sample size, age and markers of infections were extracted from the relevant studies. RESULTS: HIV, HBV and HCV are blood-borne viruses with similar modes of transmission. The categories of people at high risk of acquiring HIV-1, HBV and HCV commonly include: MSMs, FSW and IDUs. It is well established that HIV positive individuals co-infected with HBV or HCV suffer from liver pathology associated with morbidity and mortality. Moreover, HIV-infected individuals do not respond well to treatment for HBV or HCV and hence are at increased risk of hepatic toxicity. Consequently, co-infection of HIV-positive individuals with HBV and/or HCV is a global health problem of significant magnitude. Our review reveals the paucity of epidemiological data for key populations in many countries of the region. Limited number of studies exists in the MENA region on the status of HIV, HBV and HCV and their co-infections among prisoners, MSMs and FSWs. Evidence support the continued increase of the HIV epidemic among MSMs. In addition to the lack of studies on MSMs and FSWs in the MENA region, our review highlights the lack of data on the practices, characteristics, or the status of HIV infection and viral hepatitis among male sex workers selling or exchanging sex for money. CONCLUSION: The MENA countries are in urgent need of advanced research and strengthening of the data collection systems and reporting practices of these infections among key populations. PMID- 26557957 TI - Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity. AB - Because of the intimate association of obesity with type 2 diabetes mellitus (T2DM), during the last two decades, extensive research work is being conducted to find out whether the coexistence of the two is a simple association or there is a positive correlating link between the two. In this article, an attempt has been made to collect and analyse the recent developments in this field and to arrive at a conclusion on the subject. The possible role of several important factors (obtained from adipocytes/not of adipocyte origin) in linking the two has been discussed in detail. Some of the agents, specifically adiponectin, are beneficial (i.e., reduce the incidence of both), while others are harmful (i.e., increase their incidence). From the analysis, it appears that obesity and T2DM are intimately linked. PMID- 26557956 TI - New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders. AB - The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucose-lowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM) and cholecystokinin (CCK) for obesity-related diabetes. Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered. PMID- 26557959 TI - Avicenna's contribution to mechanisms of cardiovascular drugs. PMID- 26557958 TI - Integrative Modeling of Macromolecular Assemblies from Low to Near-Atomic Resolution. AB - While conventional high-resolution techniques in structural biology are challenged by the size and flexibility of many biological assemblies, recent advances in low-resolution techniques such as cryo-electron microscopy (cryo-EM) and small angle X-ray scattering (SAXS) have opened up new avenues to define the structures of such assemblies. By systematically combining various sources of structural, biochemical and biophysical information, integrative modeling approaches aim to provide a unified structural description of such assemblies, starting from high-resolution structures of the individual components and integrating all available information from low-resolution experimental methods. In this review, we describe integrative modeling approaches, which use complementary data from either cryo-EM or SAXS. Specifically, we focus on the popular molecular dynamics flexible fitting (MDFF) method, which has been widely used for flexible fitting into cryo-EM maps. Second, we describe hybrid molecular dynamics, Rosetta Monte-Carlo and minimum ensemble search (MES) methods that can be used to incorporate SAXS into pseudoatomic structural models. We present concise descriptions of the two methods and their most popular alternatives, along with select illustrative applications to protein/nucleic acid assemblies involved in DNA replication and repair. PMID- 26557961 TI - Electrophysiologic and clinico-pathologic characteristics of statin-induced muscle injury. AB - OBJECTIVES: In this study, we aimed at evaluation of electrophysiological and histopathalogical characteristics of statin-induced muscle injury as well as clinical features of patients who develop this condition in terms of frequency and pattern of evolution. MATERIALS AND METHODS: Forty patients (age 39-74 years) including 25 subjects with type 2 diabetes mellitus, 9 with cardiovascular diseases and 6 with hyperlipidemia, who were receiving atrovastatin 40 mg/day for variable period, were studied. Thirty three healthy subjects (age 31-74 years) served as control group. Creatine phosphokinease level, thyroid function, motor unit potential parameters and muscle fiber conduction velocity of biceps brachii and tibialis anterior muscles were measured. RESULTS: Creatine phosphokinase level was elevated in statin users, particularly in those with diabetes mellitus. Less than 50% of statin users experienced symptoms related to muscle injury. Muscle fiber conduction velocity of the biceps brachii muscle was significantly reduced. Statin users with diabetes mellitus showed significant changes in electrophysiological parameters as compared to those with cardiovascular diseases and hyperlipidemia. Muscle biopsies showed muscle fiber variation in size, fibrosis and mild inflammatory cell infiltration. Immunohistochemical evaluation of muscle biopsies showed positive expression of Bcl-2 and one patient showed positive P53 immunohistochemical expression with elevated level of creatine phosphokinase. CONCLUSION: Atorvastatin increased average creatine kinase, statins produce mild muscle injury even in asymptomatic subjects. Diabetic statin users were more prone to develop muscle injury than others. Muscle fiber conduction velocity evaluation is recommended as a simple and reliable test to diagnose statin-induced myopathy instead of invasive muscle biopsy. PMID- 26557962 TI - Antidiabetic effect of honey feeding in noise induced hyperglycemic rat: involvement of oxidative stress. AB - OBJECTIVES: In this study the effect of oral administration of honey on serum glucose, lipids, stress oxidative markers, and morphology of langerhans islets in noise induced hyperglycemic rats was investigated. MATERIALS AND METHODS: Male Wistar rats were divided into control, hyperglycemic, honey treated control, and honey treated hyperglycemic groups. For induction of hyperglycemia, noise stress was used. Serum glucose, triglyceride (TG), total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL)-cholesterol levels were determined before the study and at 4(th) and 8(th) weeks after the study. Markers of oxidative stress in brain were also measured. Morphology of langerhans islets in four groups was evaluated using Gomori staining method. RESULTS: Treatment of noise induced hyperglycemic rats with honey produced a hypoglycemic effect and appropriate changes regarding serum lipids in treated diabetic group at 4(th) and 8(th) weeks as compared to the control group. Meanwhile, honey treatment significantly ameliorated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in brain. Histology of langerhans islets in hyperglycemic group showed a lower number and granularity of beta cells; honey treatment produced beneficial change in this respect. CONCLUSION: Oral administration of honey in experimental model of diabetes showed a significant hypoglycemic effect and led to appropriate changes in serum lipid profiles. PMID- 26557963 TI - Antinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system. AB - OBJECTIVES: Neuropathic pain remains a clinical problem and is poorly relieved by conventional analgesics. This study was designed to determine whether maprotiline administration was effective in alleviating symptoms of neuropathic pain and whether the antinociceptive effect of maprotiline mediated through the opioid system. MATERIALS AND METHODS: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats, which resulted in thermal hyperalgesia, and mechanical and cold allodynia. Maprotiline (10, 20 and 40 mg/kg, IP) was administered on the 7(th) and 14(th) days after surgery. To study the role of the opioid system in the antinociceptive effects of maprotiline, maprotiline (20 mg/kg, IP) was administered in combination with naloxone (1 mg/kg, SC) on the 7(th) post-surgery day. Behavioral tests were done at 45 min after drug injections on the 7(th) and 14(th) days after surgery. RESULTS: Systemic administration of maprotiline blocked heat hyperalgesia, cold allodynia and reduced mechanical allodynia. Also antihyperalgesic effect of maprotiline was reversed by pretreatment with naloxone. CONCLUSION: Our results suggest that maprotiline can be considered a potential therapeutic for the treatment of neuropathic pain, and the opioid system may be involved in the antihyperalgesic effects of maprotiline. PMID- 26557960 TI - Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study. AB - Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung. PMID- 26557964 TI - Inhibition of Pseudomonas aeruginosa biofilm formation by 2,2'-bipyridyl, lipoic, kojic and picolinic acids. AB - OBJECTIVES: The inhibitory effects of iron chelators, and FeCl3 chelation on biofilm formation and swarming motility were investigated against an opportunistic human pathogen Pseudomonas aeruginosa. MATERIALS AND METHODS: The inhibitory activity of 2,2'-bipyridyl, lipoic acid, kojic acid and picolinic acid on biofilm formation of P. aeruginosa strain PAO1 and three clinical isolates (P. aeruginosa PAK01, P. aeruginosa PAK02 and P. aeruginosa PAK03) were investigated, based on crystal violet assay, and swarming motility test. RESULTS: The kojic, lipoic and picolinic acid inhibited biofilm formation by 5-33% in all tested P. aeruginosa isolates. When chelated iron was added, biofilm inhibition rates were determined to be 39-57%. Among the tested chelators against P. aeruginosa, lipoic acid (84%) and kojic acid (68%) presented the highest inhibition of swarming motility. This is the first study to report the inhibitory effect of lipoic acid on biofilm formation and swarming motility of P. aeruginosa. CONCLUSION: It is considered that lipoic and picolinic acids can serve as alternatives for the treatment of the P. aeruginosa infections by inhibiting biofilm formation. PMID- 26557965 TI - Improved viability of random pattern skin flaps with the use of bone marrow mesenchymal-derived stem cells and chicken embryo extract. AB - OBJECTIVES: Covering tissue defects using skin flaps is a basic surgical strategy for plastic and reconstructive surgery. The aim of this study was to evaluate the effects of chicken embryo extract (CEE) and bone marrow derived mesenchymal stem cells (BM-MSCs) on random skin flap survival (RSF) in rats. Using chicken embryo extract can be an ideal environment for the growth and proliferation of transplanted cells. MATERIALS AND METHODS: Forty albino male Wistar rats were divided into 4 groups; each group consisted of 10 rats. BM-MSCs and CEE were transplanted into subcutaneous tissue in the area, where the flap would be examined. On the 7(th) postoperative day, the survival areas of the flaps were measured by using digital imaging with software assistance, and tissue was collected for evaluation. RESULTS: Survival area was 19.54+/-2 in the CEE group and 17.90+/-2 in the CEE/BM-MSC group when compared to the rates of the total skin flaps, which were significantly higher than the control group (13.47+/-2) (P<0.05). The biomechanical assessment showed a slight difference, although there was no statistically significant difference between the experimental groups and the control group (P>0.05). CONCLUSION: The findings from this study demonstrated that in operative treatment with BM-MSCs and CEE transplantation could promote flap survival, but the biomechanical parameters were not contrasted with a saline injection. PMID- 26557966 TI - N-myc downstream regulated gene 2 overexpression reduces matrix metalloproteinase 2 and -9 activities and cell invasion of A549 lung cancer cell line in vitro. AB - OBJECTIVES: N-myc downstream regulated gene 2 (NDRG2) is a candidate gene for tumor suppression. The expression of NDRG2 is down-regulated in several tumors including lung cancer. The aim of this study was to explore the effect of NDRG2 overexpression on invasion, migration, and enzymatic activity of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in human lung adenocarcinoma A549 cells. MATERIALS AND METHODS: A recombinant plasmid encoding green fluorescent protein (GFP)-tagged NDRG2 (pCMV6-AC-NDRG2-GFP) was used to overexpress GFP tagged NDRG2 in A549 cells. The cells in the experimental group and those in the control group were transfected with pCMV6-AC-NDRG2-GFP and a control plasmid without NDRG2 (pCMV6-AC-GFP), respectively. Fluorescent microscopy and flowcytometry analysis of GFP expression were used to evaluate the cellular expression of GFP-tagged NDRG2 and the efficiency of transfection. The effects of NDRG2 expression on cell invasion and migration were evaluated using transwell filter migration assay. The gelatinase activity of secreted MMP-2 and MMP-9 was measured by gelatin zymography. RESULTS: Our results demonstrated the expression of GFP-tagged NDRG2 in the cytoplasm and nucleus of A549 cells. The findings of transwell assay showed that NDRG2 overexpression reduced migration and invasion of A549 cells compared to control cells. Gelatin zymography analyses revealed that NDRG2 overexpression decreased the gelatinase activity of secreted MMP-2 and MMP-9. CONCLUSION: These findings suggest that NDRG2 may be a new anti-invasion factor in lung cancer that inhibits MMPs activities. PMID- 26557967 TI - Construction of expressing vectors including melanoma differentiation-associated gene-7 (mda-7) fused with the RGD sequences for better tumor targeting. AB - OBJECTIVES: Up to now, many researches have been performed to improve the antitumoral effect of melanoma differentiation-associated gene-7 (mda-7) protein. The purpose of our research was to construct 3 expression vectors producing mda-7 in fusion with RGD (Arginine-Glycine-Aspartic acid) peptide and evaluate their expression. MATERIALS AND METHODS: mda-7 gene with two different RGD sequences was amplified by PCR then was cloned by TA-cloning system. The colonies including these genes were selected by blue-white screening, colony PCR, and sequencing, respectively. Afterward, the genes were sub-cloned into the expression vector following confirmation by colony PCR and sequencing. In addition, these constructs were transfected into 293 and Huh-7 cells for further expression analysis. The mda-7 gene expression was evaluated by RT-PCR and IF (immunofluorescence assay). DNA laddering test and trypan blue exclusion assays were performed to screen cytotoxicity of prepared plasmids. RESULTS: Three different mda-7 genes with terminal RGD peptide were cloned correctly into the expression vectors and their expression was confirmed to be suitable by RT-PCR and IF assay. It was shown that expressions were limited to those transfected, GFP shining cells. No significant cytotoxicity was observed by simple assays in all plasmid treated cells. In expressing cells, all forms of mda-7 protein were localized mainly around ER prenuclear compartment while GFP protein was distributed evenly among them. CONCLUSION: Theoretically RGD tagged mda-7 would be able to induce apoptosis with more specificity and stronger than the standard one, therefore, these new constructs may have the potential for further researches. PMID- 26557968 TI - Decellularized kidney in the presence of chondroitin sulfate as a natural 3D scaffold for stem cells. AB - OBJECTIVES: Use of biological scaffolds and automating the cells directing process with materials such as growth factors and glycosaminoglycans (GAGs) in a certain path may have beneficial effects in tissue engineering and regenerative medicine in future. In this research, chondroitin sulfate sodium was used for impregnation of the scaffolds. It is a critical component in extracellular matrix and plays an important role in signaling pathway; however, little is known about its role within mammalian development and cell linage specification. MATERIALS AND METHODS: Due to its porous and appropriate structure and for putting cells in 3D space, the kidney of BALB/c mouse was selected and decellulalized using physical and chemical methods. After decellularization, the scaffold was impregnated in chondroitin sulfate solution (CS) for 24 hr. Then, 60*10(5) human adipose-derived mesenchymal stem cells were seeded on the scaffold to assess their behavior on day 5, 10, 15, 20, and 25. RESULTS: After 48 hr, DAPI staining approved completed decellularized kidney by 1% SDS (sodium dodecyl sulfate). Migration and establishment of a number of cells to the remaining area of the glomerulus was observed. In addition, cell accumulation on the scaffold surface as well as cells migration to the depth of kidney formed an epithelium-like structure. Up to the day 15, microscopic study of different days of seeding showed the gradual adhesion of large number of cells to the scaffold. CONCLUSION: Glycosaminoglycan could be a right option for impregnation. It is used for smartification and strengthening of natural scaffolds and induction of some behaviors in stem cells. PMID- 26557969 TI - Estrogen treatment enhances neurogenic differentiation of human adipose derived stem cells in vitro. AB - OBJECTIVES: Estrogen is a sexual hormone that has prominent effects on reproductive and non-reproductive tissues. The aim of this study is to evaluate the effects of estrogen on the proliferation and neural differentiation of human adipose derived stem cells (ADSCs) during neurogenic differentiation. MATERIALS AND METHODS: Isolated human ADSCs were trans-differentiated in neural induction medium containing neurobasal medium, N2 and B27 with or without 17beta-estradiol (E2) treatment. Proliferation rate and neural differentiation of human ADSCs were assessed using MTT assay, immunostaining and real time RT- PCR analysis, respectively. RESULTS: Analysis of data show that estradiol treatment can significantly increase proliferation rate of differentiated cells (P<0.05). Immunocytochemical and real time RT-PCR analysis revealed that the expression of precursor and mature neuronal markers (nestin and MAP2) was significantly higher in the E2 treated cell cultures when compared to the untreated cell cultures (P<0.05). CONCLUSION: According to our findings, estrogen can promote proliferation and neuronal differentiation of human ADSCs. PMID- 26557970 TI - Chronic effects of aerobic exercise on gene expression of LOX-1 receptor in the heart of rats fed with high fat diet. AB - OBJECTIVES: Lectin-like low density lipoprotein receptor (LOX-1) has pivot role in vascular complications, which is upregulated in numerous pathological conditions. Since exercise has beneficial effects in prevention of hyperlipidemic complications, present study examined protective effects of aerobic exercise through reduction of LOX-1 expression in heart during dyslipidemia. MATERIALS AND METHODS: Four groups of rats were used (N=25): Normal, Normal and exercise, High fat and High fat and exercise. High fat diet (HFD) was made by adding 10% animal oil, 2% cholesterol and 0.5% colic acid to standard rodent chow. Exercise protocol consisted of swimming 1 hr/day, and 5 days/week for 8 weeks. Plasma lipids were evaluated at the end of experiment, 48 hr after final session of exercise. At the end, rats were sacrificed and heart was removed for determination of malondialdehyde (MDA) content, and LOX-1 expression. RESULTS: HFD meaningfully changed lipid profile (>50%), but chronic exercise had no significant effects on lipid profile. LOX-1 expression was significantly increased in heart of rats fed with HFD, while swimming exercise considerably reduced gene expression of LOX-1. MDA content was significantly enhanced in rats fed with HFD (4.37+/-0.6 nmol/mg, P<0.01) compared to normal group (1.56+/-0.48 nmol/mg), whereas swimming exercise decreased MDA level of heart in rats fed with HFD (2.28+/-0.32, P<0.01). CONCLUSION: Findings indicated that swimming exercise is able to diminish heart expression of LOX-1 receptor concomitant reduction of oxidative stress. Since these parameters are involved in generation of dyslipidemic complications, swimming exercise is a good candidate to reduce these complications. PMID- 26557971 TI - Sphingosine 1-phosphate interacts with Survivin pathway to enhance tumorigenesis in cancer cells. AB - OBJECTIVES: Degradation of sphingosine 1-phosphate (S1P), as a bioactive lipid, or deregulation of its production involves in tumor progression, metastasis and chemoresistance. Since the tumor progression effects of S1P and its mechanism in chronic lymphoblastic leukemia and non-small cell lung cancer is not fully understood, we investigated the role and one of the mechanisms of S1P in tumor progression of SKW3 and H1299 cells. MATERIALS AND METHODS: The effects of S1P on proliferation, invasion and migration was studied using MTT assay, soft-agar colony forming assay and trans-well migration assay, respectively. In order to find out the mechanisms of S1P action, the role of S1P on expression of Survivin gene was assessed by real-time RT-PCR. RESULTS: Our results demonstrated that although invasion was shown only in H1299 cells, low concentration of S1P, especially at 1 MUM, mediated proliferation and migration in both cell lines. In addition, these effects of S1P in tumor progression are S1P receptor-dependent, and Survivin plays a key role in S1P tumorigenesis. CONCLUSION: Our results confirmed the involvement of S1P and its receptors in tumor progression of SKW3 and H1299. We also investigated another mechanism of S1P involved in cell survival, tumor progression, and Survivin signaling. In conclusion, data demonstrated the importance of this molecule as a target for designing new anticancer drugs such as anti-S1P monoclonal antibody for inhibiting major downstream signaling, which plays significant role in tumorigenesis. PMID- 26557972 TI - Propofol differentially inhibits the release of glutamate, gamma-aminobutyric acid and glycine in the spinal dorsal horn of rats. AB - OBJECTIVES: Propofol (2, 6-diisopropylphenol) is an intravenous anesthetic that is commonly used for the general anesthesia. It is well known that the spinal cord is one of the working targets of general anesthesia including propofol. However, there is a lack of investigation of the effects of propofol on spinal dorsal horn which is important for the sensory transmission of nociceptive signals. The objective of this study was to investigate the effects of increasing dosage of propofol on the release of glutamate (Glu), gamma-aminobutyric acid (GABA) and glycine (Gly) in the spinal dorsal horn. MATERIALS AND METHODS: The efflux of Glu, GABA or Gly in the spinal dorsal horn of rats was detected using transverse spinal microdialysis under an awake condition and various depths of propofol anesthesia. The infusion rates of propofol were, in order, 400 ug/(kg.min), 600 ug/(kg.min) and 800 ug/(kg.min), with a 20 min infusion period being maintained at each infusion rate. RESULTS: Propofol decreased the glutamate efflux within spinal dorsal horn in a dose-dependent manner, and the maximum decrease was 56.8 +/- 6.0% at high-dose propofol infusion producing immobility. The inhibitory GABA and Gly efflux was also decreased about 15-20% at low-dose propofol infusion only producing sedation, but did not continue to drop with higher doses of propofol. CONCLUSION: Propofol decreased both excitatory and inhibitory amino acids efflux in spinal dorsal horn, and the preferential suppression of the excitatory amino acid might be associated with the analgesic effect of propofol. PMID- 26557973 TI - Squid ink polysaccharide reduces cyclophosphamide-induced testicular damage via Nrf2/ARE activation pathway in mice. AB - OBJECTIVES: Cyclophosphamide (CP) toxicity on testis was hampered by squid ink polysaccharide (SIP) via restoration of antioxidant ability in our previous investigations. This study investigated roles of Nrf2/ARE signal pathway in testis of treated mice. MATERIALS AND METHODS: Male Kunming mice were employed to undergo treatment with SIP and/or CP. Protein levels of Nrf2, keap-1, histone deacetylase 2 (HDAC2), quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO 1) and phosphorylation level of protein kinase C (PKC) in testis were evaluated by Western blotting. RESULTS: Data showed that SIP elevated expressions of NQO-1 and HO-1 genes, two downstream target molecules of Nrf2, via activating Nrf2 to play preventive roles on CP-treated testis, and further discovered that upstream regulators of Nrf2, keap-1, HDAC2, and PKC, were concerned with the regulation of Nrf2. CONCLUSION: These results suggest that SIP could effectively weaken CP associated testicular damage via Nrf2/ARE signal pathway. PMID- 26557974 TI - Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis. AB - OBJECTIVES: Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. MATERIALS AND METHODS: The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. RESULTS: The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. CONCLUSION: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid. PMID- 26557975 TI - The autism inpatient collection: methods and preliminary sample description. AB - BACKGROUND: Individuals severely affected by autism spectrum disorder (ASD), including those with intellectual disability, expressive language impairment, and/or self-injurious behavior (SIB), are underrepresented in the ASD literature and extant collections of phenotypic and biological data. An understanding of ASD's etiology and subtypes can only be as complete as the studied samples are representative. METHODS: The Autism Inpatient Collection (AIC) is a multi-site study enrolling children and adolescents with ASD aged 4-20 years admitted to six specialized inpatient psychiatry units. Enrollment began March, 2014, and continues at a rate of over 400 children annually. Measures characterizing adaptive and cognitive functioning, communication, externalizing behaviors, emotion regulation, psychiatric co-morbidity, self-injurious behavior, parent stress, and parent self-efficacy are collected. ASD diagnosis is confirmed by the Autism Diagnostic Observation Schedule - 2 (ADOS-2) and extensive inpatient observation. Biological samples from probands and their biological parents are banked and processed for DNA extraction and creation of lymphoblastoid cell lines. RESULTS: Sixty-one percent of eligible subjects were enrolled. The first 147 subjects were an average of 12.6 years old (SD 3.42, range 4-20); 26.5 % female; 74.8 % Caucasian, and 81.6 % non-Hispanic/non-Latino. Mean non-verbal intelligence quotient IQ = 70.9 (SD 29.16, range 30-137) and mean adaptive behavior composite score = 55.6 (SD 12.9, range 27-96). A majority of subjects (52.4 %) were non- or minimally verbal. The average Aberrant Behavior Checklist - Irritability Subscale score was 28.6, well above the typical threshold for clinically concerning externalizing behaviors, and 26.5 % of the sample engaged in SIB. Females had more frequent and severe SIB than males. CONCLUSIONS: Preliminary data indicate that the AIC has a rich representation of the portion of the autism spectrum that is understudied and underrepresented in extant data collections. More than half of the sample is non- or minimally verbal, over 40 % have intellectual disability, and over one quarter exhibit SIB. The AIC is a substantial new resource for study of the full autism spectrum, which will augment existing data on higher-functioning cohorts and facilitate the identification of genetic subtypes and novel treatment targets. The AIC investigators welcome collaborations with other investigators, and access to the AIC phenotypic data and biosamples may be requested through the Simons Foundation (www.sfari.org). PMID- 26557976 TI - Are females more variable than males in gene expression? Meta-analysis of microarray datasets. AB - BACKGROUND: The majority of preclinical biomedical research involves studies of males rather than females. It is thought that researchers have avoided females based on the idea that female traits are more variable than those of males because of cyclic variation in effects of ovarian hormones. METHODS: To test the assumption of inherently greater female variability, we analyzed 293 microarray datasets measuring gene expression in various tissues of mice and humans, comprising analysis of more than 5 million probes. RESULTS: Meta-analysis showed that on average, male gene expression is slightly more variable than that of females although the difference is small. We also tested if the X chromosome of humans shows greater variability in gene expression in males than in females, as might be expected because of hemizygous exposure of polymorphic X alleles but again found little sex difference. CONCLUSION: Our analysis supports and extends previous studies reporting no overall greater phenotypic variability in females. PMID- 26557977 TI - Sex differences in substance use, health, and social functioning among opioid users receiving methadone treatment: a multicenter cohort study. AB - BACKGROUND: Despite the growing numbers of men and women with opioid use disorder in Canada, sex-specific issues in treatment have not been re-examined in the current population of patients with opioid addiction. We aimed to evaluate sex differences in substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid use disorder in Ontario, Canada. METHODS: We recruited 503 participants with opioid dependence disorder receiving methadone maintenance treatment. We collected data on demographics, treatment characteristics, psychiatric history, addiction severity, and drug use patterns through urinalysis. We performed adjusted univariate analyses and logistic regression to identify distinct factors affecting men and women. RESULTS: Among our sample of 54 % (n = 266) men and 46 % women (n = 226) with mean age 38.3 years, less than half of participants were employed (35.6 %) and married (31.8 %) and had completed a high school education (27.9 %). Compared to men, women had frequent physical and psychological health problems, family history of psychiatric illness, and childcare responsibilities and began using opioids through a physician prescription. Men had higher rates of employment, cigarette smoking, and cannabis use compared to women. CONCLUSIONS: Our results have revealed different patterns of substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid addiction in Ontario, Canada. This information can be used to develop an integrative treatment regimen that caters to the individual needs of men and women, as well as to inform methadone treatment protocols to include specialized services (including vocational counseling, childcare and parenting assistance, medical assistance, relationship or domestic violence counseling, etc.) and increase their availability and accessibility on a larger scale. PMID- 26557978 TI - Sexual dimorphism in the hypophysiotropic tyrosine hydroxylase-positive neurons in the preoptic area of the teleost, Clarias batrachus. AB - BACKGROUND: Dopamine (DA) neurons in the anteroventral periventricular nucleus (AVPV) in the preoptic area (POA) of mammals express estrogen receptors, regulate luteinizing hormone (LH) secretion, and show distinct sexual dimorphism. In teleosts, hypophysiotropic DA neurons of the nucleus preopticus periventricularis (NPP), located in the anteroventral POA, express estrogen receptors, innervate LH cells, and emerged as a neuroanatomical substrate for inhibiting LH cells. Interestingly, the NPP and AVPV seem to share several similarities. Whether DAergic neurons in the NPP show sexual dimorphism is, however, not known. Based on the proposed homology to AVPV and previous studies showing greater tyrosine hydroxylase (TH) mRNA and enzyme activity levels in the brain of female catfish, we hypothesize that females have greater number of DAergic neurons in the NPP and correspondingly more TH-immunoreactive fiber innervation of the pituitary. METHODS: Adult, male and female Clarias batrachus collected during the prespawning phase of their reproductive cycle were used. Fish were anesthetized and perfused transcardially with phosphate-buffered saline (pH 7.4) and 4 % paraformaldehyde in phosphate buffer. Sections through the rostro-caudal extent of the POA and pituitary were processed for TH immunofluorescence. Using double immunofluorescence, the association between TH-immunoreactive fibers and LH cells in the pituitary was explored. Sections were analyzed using semiquantitative analysis. RESULTS: NPP in POA of C. batrachus has two distinct subdivisions, viz, anterior (NPPa) and posterior (NPPp), and TH neurons were observed in both the subdivisions. Compared to that in the males, a significantly higher (P < 0.05) number of TH neurons was consistently observed in the NPPa of females. TH neurons in NPPp, however, showed no difference in the number or immunoreactivity. Since DA neurons in NPPa are hypophysiotropic, we compared TH-fiber innervation of the pituitary in both sexes. Compared to males, proximal pars distalis and LH cells in this region of the pituitary in females were densely innervated by TH fibers. CONCLUSIONS: Neurons of NPPa and their innervation to the pituitary seem to be a distinct sexually dimorphic DAergic system in C. batrachus. The DAergic system may serve as a component of the neural mechanisms controlling the sexually dimorphic LH surge in teleosts. Given the similarities shared by NPPa and AVPV, homology between these two nuclei is suggested. PMID- 26557980 TI - Editorial. PMID- 26557981 TI - Factors predicting use of laxatives in outpatients stabilized on clozapine. AB - Constipation is a common and sometimes fatal side effect of clozapine treatment. In this study, we aimed to identify factors associated with clozapine-induced constipation. Data on 202 outpatients stabilized on clozapine treatment were collected. Of these, 71 patients (35%) had a current prescription for laxatives (a proxy for the presence of constipation). Mean clozapine dose was 400.4 mg/day in those prescribed laxatives and 390.1 mg/day in those not prescribed laxatives (p = 0.67), while mean clozapine plasma concentration was 0.53 mg/l and 0.49 mg/l, respectively (p = 0.29). Patients using laxatives had on average 29% higher norclozapine concentrations (mean = 0.34 mg/l) than those who did not use laxatives (mean = 0.27 mg/l; p = 0.046). Laxative use was more common in female patients (49.1%) than male patients (29.1%; p < 0.01). Prescribers should be vigilant for constipation at any dose or plasma concentration of clozapine and should be mindful that male patients may be undertreated. Norclozapine concentrations may predict clozapine-induced constipation. PMID- 26557979 TI - Sex differences in protein expression in the mouse brain and their perturbations in a model of Down syndrome. AB - BACKGROUND: While many sex differences in structure and function of the mammalian brain have been described, the molecular correlates of these differences are not broadly known. Also unknown is how sex differences at the protein level are perturbed by mutations that lead to intellectual disability (ID). Down syndrome (DS) is the most common genetic cause of ID and is due to trisomy of human chromosome 21 (Hsa21) and the resulting increased expression of Hsa21-encoded genes. The Dp(10)1Yey mouse model (Dp10) of DS is trisomic for orthologs of 39 Hsa21 protein-coding genes that map to mouse chromosome 10 (Mmu10), including four genes with known sex differences in functional properties. How these genes contribute to the DS cognitive phenotype is not known. METHODS: Using reverse phase protein arrays, levels of ~100 proteins/protein modifications were measured in the hippocampus, cerebellum, and cortex of female and male controls and their trisomic Dp10 littermates. Proteins were chosen for their known roles in learning/memory and synaptic plasticity and include components of the MAPK, MTOR, and apoptosis pathways, immediate early genes, and subunits of ionotropic glutamate receptors. Protein levels were compared between genotypes, sexes, and brain regions using a three-level mixed effects model and the Benjamini-Hochberg correction for multiple testing. RESULTS: In control mice, levels of approximately one half of the proteins differ significantly between females and males in at least one brain region; in the hippocampus alone, levels of 40 % of the proteins are significantly higher in females. Trisomy of the Mmu10 segment differentially affects female and male profiles, perturbing protein levels most in the cerebellum of female Dp10 and most in the hippocampus of male Dp10. Cortex is minimally affected by sex and genotype. Diverse pathways and processes are implicated in both sex and genotype differences. CONCLUSIONS: The extensive sex differences in control mice in levels of proteins involved in learning/memory illustrate the molecular complexity underlying sex differences in normal neurological processes. The sex-specific abnormalities in the Dp10 suggest the possibility of sex-specific phenotypic features in DS and reinforce the need to use female as well as male mice, in particular in preclinical evaluations of drug responses. PMID- 26557982 TI - Amelioration of deficit syndrome of schizophrenia by norepinephrine reuptake inhibitor. AB - OBJECTIVE: Negative symptoms are a significant barrier to successful functional outcome and recovery in individuals with schizophrenia and their management is not unproblematic. Reboxetine is a norepinephrine reuptake inhibitor (NRI). Previous studies regarding the useful effects of reboxetine on deficit symptoms of schizophrenia have resulted in inconsistent results. The present study therefore evaluated the effectiveness of reboxetine as an adjunctive treatment in a group of schizophrenic patients with prominent negative symptoms. METHOD: A total of 50 male inpatients meeting diagnosis of schizophrenia entered into a 12 week parallel group, double-blind study for random assignment to reboxetine (n = 25 patients) or placebo (n = 25 patients). The inclusion criterion, in addition to the diagnosis of schizophrenia, was the existence of obvious negative symptoms for a duration of at least 2 years. The Scale for Assessment of Negative Symptoms (SANS) was used as the primary outcome measure. The Scale for Assessment of Positive Symptoms (SAPS), Simpson Angus Scale (SAS), Hamilton Rating Scale for Depression (HAM-D) and Mini-Mental Status Examination (MMSE) were used for comparison of the intervening parameters in this study. RESULTS: According to the findings, 76% of patients in the target group showed some positive response to reboxetine compared with 24% in the control group (p < 0.01). The mean total score of SANS in the reboxetine group decreased significantly from 79.94 +/- 1.20 to 74.23 +/- 4.07 (p < 0.0001) at the end of the study; such an improvement was not significant in the placebo group with a decrease from 80.42 +/- 2.46 to 79.08 +/- 5.83 (p < 0.29). Changes of SAPS were insignificant in both groups. Effect size analysis for changes of SANS at the end of assessment indicated a large improvement with reboxetine (Cohen's d = 2.91). CONCLUSION: Reboxetine, as an adjuvant to haloperidol, may have a helpful effect on the deficit syndrome of schizophrenia. PMID- 26557983 TI - Metabolic status and resistin in chronic schizophrenia over a 2-year period with continuous atypical antipsychotics. AB - BACKGROUND: Common adverse effects of atypical antipsychotic treatments for schizophrenia are weight gain and lipid metabolism abnormality. We aimed to identify the signs of metabolic problems with continuous atypical antipsychotic treatment for schizophrenia over a 2-year period. METHODS: The participants were 68 schizophrenic patients (29 males, 39 females; ages 53.4 +/- 13.5 years old). Changes in carbohydrate metabolism and changes in physical characteristics were studied over a 2-year period. In addition, functional single nucleotide polymorphisms in the transcriptional regulatory region of the resistin gene were examined. RESULTS: We found no changes in the mental state of the participants over a 2-year period. Patients did show a significant decrease in total cholesterol and hemoglobin A1c levels, although physical changes such as body mass index and abdominal girth, were not observed. The amount of resistin may not be associated with mental states and physical parameters. CONCLUSIONS: We could not find physical factors related to metabolic changes of antipsychotics in this 2-year study. However, several psychological factors, such as health-related thoughts and behaviors, should be studied in the future. PMID- 26557984 TI - Enhancing adherence, subjective well-being and quality of life in patients with schizophrenia: which role for long-acting risperidone? AB - AIM: This study evaluated adherence to treatment, quality of life and subjective well-being in patients with psychosis treated with long-acting injectable risperidone. Subjects enrolled were part of a larger study where patients were observed in an adherence to treatment program of the University of Rome Tor Vergata. MATERIALS AND METHODS: A total of 27 nonadherent patients (21 men, six women; mean age: 36.1 years; range: 23-63 years) were enrolled. Maximum observational period was 30 months. RESULTS: A total of 12 patients were under treatment for 30 months (44.44%) but only nine had a valid 30-month follow up, while the remaining three patients initially treated at our unit continued long acting risperidone at their local centre. Reductions of monthly mean values of Scale for the Assessment of Positive Symptoms (SAPS) [repeated measures analysis of variance (rm-ANOVA): p < 0.0001] and Scale for Assessment of Negative Symptoms (SANS) (p < 0.0001), increase of monthly mean values of Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) (p < 0.0001) and Schizophrenia Quality of Life Scale (S-QoL) (p < 0.01) were observed. Significant differences with respect to SAPS baseline values from the sixth month, SANS baseline values from the seventh month, SWN baseline values from the eighth month, S-QoL baseline values from the eighteenth month were shown in post hoc tests. Reduction of SAPS mean values was associated with increase of SWN (p < 0.0001) and S-QoL (p < 0.0001) mean values as demonstrated by correlation analysis. The same inverse correlation was found between reduction of SANS mean values and increases of SWN (p < 0.0001) and S-QoL (p = 0.0001) mean values. CONCLUSIONS: Long-term treatment with long acting risperidone may be associated with improvement to adherence to therapy and quality of life. Patients may show improvement in psychopathological symptoms, subjective well-being and quality of life. PMID- 26557985 TI - Development of the My Medicines and Me (M3Q) side effect questionnaire for mental health patients: a qualitative study. AB - OBJECTIVE: The objective of this study was to assess the acceptability, content validity and usability of the My Medicines and Me (M3Q) self-report side effect questionnaire. METHODS: Eight focus groups consisting of mental health patients, carers, general practitioners, psychiatrists, mental health nurses and pharmacists were conducted, involving 78 participants. Two researchers independently examined the transcriptions and analysed the data thematically using an inductive method. RESULTS: The findings supported changes to the formatting, length and phrasing of questions in the original version of the questionnaire. Although the groups provided differing views on the usability of the M3Q in clinical practice, the patient and carer groups were unconditionally in favour of such a tool to be used systematically to describe patients' subjective experiences with side effects. CONCLUSION: The differing contribution made by all groups involved in the administration and completion of the M3Q assisted with content validity of the questionnaire. The acceptability and usability of this novel side effect questionnaire was also explored, with many participants agreeing it was a necessary tool for a patient centred approach to treatment. Following implementation of the changes to the current format of the questionnaire, investigation into the uptake and use in clinical practice should be carried out. PMID- 26557986 TI - Two cases of long-acting paliperidone in adolescence. AB - Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance. PMID- 26557987 TI - Mirtazapine for antipsychotic-induced acute akathisia: a systematic review and meta-analysis of randomized placebo-controlled trials. AB - OBJECTIVE: To conduct a systematic review and meta-analysis of randomized placebo controlled trials of mirtazapine for the treatment of antipsychotic-induced acute akathisia (AIAA). METHODS: Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as www.clinicaltrials.gov, www.controlled-trials.com, and www.clinicalstudyresults.org. The study eligibility criteria were randomized, double-blind clinical trials comparing mirtazapine with placebo for AIAA with standardized rating for akathisia as outcome measure. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (response rate and complete remission) and treatment effects were expressed as Mantel-Haenszel risk ratio (RR). Fixed-effect meta-analysis was performed as heterogeneity was not significant. Number need to treat (NNT) as a measure of relative treatment effectiveness was calculated. RESULTS: A systematic review of the literature revealed six studies that had assessed mirtazapine for the treatment of AIAA. Of these, two studies (n = 86) met the review inclusion criteria and were included in the final analysis. A meta analysis was performed to see the effect size of response rate and complete remission. For response rate, RR was 6.67 [95% confidence interval (CI) 2.14 20.78], favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.001, NNT 4, 95% CI 2.6-8.6). For complete remission, RR was 6.20 (95% CI 1.74-22.08), favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.005, NNT 5, 95% CI 2.9-11.6). CONCLUSIONS: Although limited to only two studies and small sample, existing data support the efficacy of mirtazapine for the treatment of AIAA, with one in four patients showing partial response and one in five patients showing complete remission. PMID- 26557988 TI - Paradoxical worsening of tics with haloperidol. PMID- 26557989 TI - Do elderly patients have the most to gain from laparoscopic surgery? AB - Populations are aging worldwide, people are living longer, and the surgical needs of elderly patients are rising. Laparoscopic techniques have become more common with improved training, surgeon skill and evidence of improved outcomes. Benefits of laparoscopy include decreased blood loss, postoperative pain, and hospital length of stay; improved mobilization, quicker return to normal activity; and fewer pulmonary, thrombotic, and abdominal wall complications. Indeed, for many common pathologies laparoscopy has become the gold standard, unless contraindicated. It has been questioned as to whether elderly patients can reap the same benefits from laparoscopic surgery. The concern in elderly patients is that physiologic demands may outweigh the benefit seen in younger patients. This question stems from concerns related to longer operative times, increased technical challenge, as well as the impact of physiologic demands of pneumoperitoneum and patient positioning. However, with anesthesia and adequate perioperative cardiac care, there is no evidence that these factors lead to worse clinical outcomes in elderly patients. In contrast, perhaps elderly patients - with increased prevalence of multi-morbidity, geriatric syndromes and diminished physiologic reserve - have the most to gain from a laparoscopic approach. PMID- 26557990 TI - Clinical presentation of eating disorders in young males at a tertiary setting. AB - BACKGROUND: Young males with eating disorders are a neglected study population in eating disorders. The aim of this study was to provide knowledge about the clinical presentation of eating disorders in young males. METHODS: The data source was the Helping to Outline Paediatric Eating Disorders (HOPE) Project (N ~ 1000), a prospective, ongoing registry comprising consecutive paediatric (<18 years) tertiary eating disorder referrals. Young males with DSM-5 eating disorders (n = 53) were compared with young females with eating disorders (n = 704). RESULTS: There was no significant difference in the prevalence of diagnosis of bulimia nervosa (2 % vs 11 %, p = 0.26) among sexes. Males had comparable duration of illness (9 months; p = 0.28) and a significantly earlier age of onset (M = 12 years; p <0.001). Shape concern (2.39 vs 3.57, p <0.001) and weight concern (1.97 vs 3.09, p <0.001) were lower in males, and body mass index z score (-1.61 vs -1.42, p = 0.29) and medical compromise (odds ratio [OR] = 0.64, 95 % CI: 0.36, 1.12) were comparable. Males had a two-folder higher odds of being diagnosed with unspecified feeding or eating disorders (40 % vs 22 % for females, p = 0.004). Driven exercise to control weight and shape was common and comparable in prevalence among males and females (51 % vs 47 %, p = 0.79) and males were less likely to present with self-induced vomiting (OR = 0.23, 95 % CI: 0.09, 0.59). CONCLUSION: Boys with eating disorders are an understudied group with similarities and differences in clinical presentation from girls with eating disorders. Parents and physicians are encouraged to consider changes in weight, disturbed vital signs, and driven, frequent exercise for the purposes of controlling weight or shape, as possible signs of eating disorders among male children. Diagnostic classification, assessment instruments, conceptualisation, and treatment methods need to be refined to improve application to young males. PMID- 26557991 TI - Depression in military medicine cadets: a cross-sectional study. AB - BACKGROUND: Military medicine cadets undergo strenuous military training alongside demanding medical studies. This stressful and complex educational environment can lead to the emergence of depressive symptoms. We investigated the prevalence of depressive symptoms in a cohort of military medicine cadets. METHODS: We conducted a descriptive questionnaire-based cross-sectional study among Greek military medicine cadets in the undergraduate program of the Hellenic Military School of Combat Support Officers. The Greek translation of the Zung self-rating depression scale questionnaire was used to screen for the presence of depressive symptoms. In addition, demographic, academic and dietary information was collected. The Shapiro-Wilk test of normality, Pearson correlation test, Chi square test, t-test and Mann Whitney U test were employed for statistical analysis. RESULTS: We enrolled 55 female and 91 male military medicine cadets with a mean age of 19.84 years (SD = 0.99). The mean Zung crude score was 43.32 (SD = 4.55): 42.8 (SD = 4.43) for female cadets and 43.64 (SD = 4.6) for male cadets. Cadets were further subdivided into low and high risk groups for the presence of depressive symptoms. We identified 57 (39 %) cadets with a total Zung crude score of 45 or above: 21 females and 36 males. Statistical analysis did not reveal any significant differences between the two groups based on gender, year of training, academic performance, alcohol consumption, smoking status, vitamin supplementation, dietary habits or BMI. CONCLUSIONS: We report a high prevalence of depressive symptoms in a cohort of military medicine cadets that underscores the need for effective screening and appropriate and timely interventions. We did not identify any related risk factors. Military medicine cadets are exposed to a challenging military and medical training environment, and thus represent a group at risk for development of depression. PMID- 26557992 TI - Accidental invisible intrathoracic disseminated pT4-M1a: a distinct lung cancer with favorable prognosis. AB - OBJECTIVE: In the 7(th) edition of the TNM classification of malignant tumors, the prognosis for pT4-M1a stage IV lung cancer is better than for stage pIIIB. Subgroups of lung cancer patients who underwent incomplete resection (R1/R2) have a favorable prognosis. This study compares the prognosis between cases of invisible local residual disease and intrathoracic disseminated pT4-M1aIV. METHODS: Patient characteristics and histological and molecular profiles were retrospectively collected for lung cancer patients who underwent resection intended to be curative but were accidentally incomplete. All patients were divided into either a local residual group or an intrathoracic disseminated pT4M1a group. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier and Cox regression models. RESULTS: In total, 1,483 consecutive lung cancer patients receiving thoracotomies at Guangdong Lung Cancer Institute were retrospectively analyzed. Fifty-eight patients receiving incomplete resections (R1/R2) were enrolled, including 38 patients with local residual cancer (2.6% of all patients) and 20 patients with disseminated pM1a (1.3%). Patient characteristics, and histological and molecular profiles of the two groups were different. Compared to the local residual group, the disseminated pT4-M1a group contained more females (P=0.002), more patients younger than 60 years of age (P=0.028), more non-smokers (P=0.037), more adenocarcinomas (20/20 vs. 20/38, P<0.001), more adenocarcinomas with lepidic pattern (11/20 vs. 4/38, P<0.001), higher carcinoembryonic antigen (CEA) levels (P=0.06), higher epidermal growth factor receptor (EGFR) mutation rates (16/20 vs. 7/38, P<0.001), a higher R2/R1 resection ratio (P=0.013), a higher advanced stage IV/IIIB ratio (P<0.001), but fewer lymph node metastases (P=0.013). Median PFS for the local residual and disseminated pT4-M1a groups was 9.0 and 18.0 months, respectively [95% confidence interval (CI), 5.285-16.715; P =0.099]. Median OS was 15.0 and 45.0 months, respectively (95% CI, 18.972-39.028; P=0.001). Cox regression analysis revealed that group (local residual vs. disseminated pT4-M1a) was the only independent prognostic factor (P=0.044) for OS. CONCLUSIONS: Accidental invisible intrathoracic disseminated pT4-M1a may be a distinct lung cancer subtype with a favorable prognosis. The prolonged PFS and OS might reflect the natural history of this distinct subtype, together with a favorable response to EGFR tyrosine kinase inhibitors (EGFR-TKI). For asymptomatic and slow-growing accidental pT4 M1a disease, the role of a wait-and-see strategy and the appropriate timing of systemic treatment require further investigation. PMID- 26557994 TI - Single-Incision Single-Instrument Adnexal Surgery in Pediatric Patients. AB - Introduction. Pediatric surgeons often practice pediatric gynecology. The single incision single-instrument (SISI) technique used for appendectomy is applicable in gynecologic surgery. Methods. We retrospectively analyzed the records of patients undergoing pelvic surgery from 2008 to 2013. SISI utilized a 12 mm transumbilical trocar and an operating endoscope. The adnexa can be detorsed intracorporeally or extracorporealized via the umbilicus for lesion removal. Results. We performed 271 ovarian or paraovarian surgeries in 258 patients. In 147 (54%), the initial approach was SISI; 75 cases (51%) were completed in patients aged from 1 day to 19.9 years and weighing 4.7 to 117 kg. Conversion to standard laparoscopy was due to contralateral oophoropexy, solid mass, inability to mobilize the adnexa, large mass, bleeding, adhesions, or better visualization. When SISI surgery was converted to Pfannenstiel, the principal reason was a solid mass. SISI surgery was significantly shorter than standard laparoscopy. There were no major complications and the overall cohort had an 11% minor complication rate. Conclusion. SISI adnexal surgery is safe, quick, inexpensive, and effective in pediatric patients. SISI was successful in over half the patients in whom it was attempted and offers a scarless result. If unsuccessful, the majority of cases can be completed with standard multiport laparoscopy. PMID- 26557993 TI - No Association of BDNF, COMT, MAOA, SLC6A3, and SLC6A4 Genes and Depressive Symptoms in a Sample of Healthy Colombian Subjects. AB - Background. Major depressive disorder (MDD) is the second cause of years lived with disability around the world. A large number of studies have been carried out to identify genetic risk factors for MDD and related endophenotypes, mainly in populations of European and Asian descent, with conflicting results. The main aim of the current study was to analyze the possible association of five candidate genes and depressive symptoms in a Colombian sample of healthy subjects. Methods and Materials. The Spanish adaptation of the Hospital Anxiety and Depression Scale (HADS) was applied to one hundred eighty-eight healthy Colombian subjects. Five functional polymorphisms were genotyped using PCR-based assays: BDNF Val66Met (rs6265), COMT-Val158Met (rs4680), SLC6A4-HTTLPR (rs4795541), MAOA uVNTR, and SLC6A3-VNTR (rs28363170). Result. We did not find significant associations with scores of depressive symptoms, derived from the HADS, for any of the five candidate genes (nominal p values >0.05). In addition, we did not find evidence of significant gene-gene interactions. Conclusion. This work is one of the first studies of candidate genes for depressive symptoms in a Latin American sample. Study of additional genetic and epigenetic variants, taking into account other pathophysiological theories, will help to identify novel candidates for MDD in populations around the world. PMID- 26557995 TI - Phenolic Extract from Moringa oleifera Leaves Inhibits Key Enzymes Linked to Erectile Dysfunction and Oxidative Stress in Rats' Penile Tissues. AB - This study was designed to determine the antioxidant properties and inhibitory effects of extract from Moringa oleifera leaves on angiotensin-I-converting enzyme (ACE) and arginase activities in vitro. The extract was prepared and phenolic (total phenols and flavonoid) contents, radical (nitric oxide (NO), hydroxyl (OH)) scavenging abilities, and Fe(2+)-chelating ability were assessed. Characterization of the phenolic constituents was done via high performance liquid chromatography-diode array detection (HPLC-DAD) analysis. Furthermore, the effects of the extract on Fe(2+)-induced MDA production in rats' penile tissue homogenate as well as its action on ACE and arginase activities were also determined. The extract scavenged NO (*) , OH (*) , chelated Fe(2+), and inhibited MDA production in a dose-dependent pattern with IC50 values of 1.36, 0.52, and 0.38 mg/mL and 194.23 ug/mL, respectively. Gallic acid, chlorogenic acid, quercetin, and kaempferol were the most abundant phenolic compounds identified in the leaf extract. The extract also inhibited ACE and arginase activities in a dose-dependent pattern and their IC50 values were 303.03 and 159.59 ug/mL, respectively. The phenolic contents, inhibition of ACE, arginase, and Fe(2+)-induced MDA production, and radical (OH (*) , NO (*) ) scavenging and Fe(2+)-chelating abilities could be some of the possible mechanisms by which M. oleifera leaves could be used in the treatment and/or management of erectile dysfunction. PMID- 26557997 TI - A welcome from the Editor-in-Chief. PMID- 26557996 TI - The Accordion Maneuver: A Noninvasive Strategy for Absent or Delayed Callus Formation in Cases of Limb Lengthening. AB - The distraction osteogenesis (DO) technique has been used worldwide to treat many orthopaedic conditions. Although successful, absent or delayed callus formation in the distraction gap can lead to significant morbidities. An alternate cycle of distraction-compression (accordion maneuver) is one approach to accelerate bone regeneration. The primary aim of our study is to report our experience with the accordion maneuver during DO and to provide a detailed description of this technique, as performed in our center. The secondary aim is to present a review of the literature regarding the use of accordion maneuver. We reviewed the database of all patients undergoing limb lengthening from the year of 1997 to 2012. Four patients (6.15%) out of 65 showed poor bone regenerate in their tibiae and therefore accordion maneuver was applied for a mean of 6.75 weeks. Of these, three patients have had successful outcome with this technique. The literature showed that this technique is successful approach to trigger bone healing. However, details of how and when to apply this combination of distraction compression forces were lacking. In conclusion, the accordion technique is safe noninvasive approach to promote bone formation, thus avoiding more invasive surgical procedures in cases of poor callus formation in limb lengthening. PMID- 26557998 TI - Robotic partial nephrectomy: The new horizon. AB - BACKGROUND: There has been an exponential growth in the reporting of series of robotic partial nephrectomy (RPN). We review the technique of RPN and the outcomes from large single-centre series of RPN. METHODS: We searched databases to identify original articles related to RPN. For the technical aspects, we describe our technique and provide a general review of previous work. For outcomes, we reviewed previous reports using more rigid criteria, including only single-institution studies with at least 50 patients undergoing RPN. RESULTS: We found seven retrospective studies that met our criteria, with a total of 701 patients. Mean tumour size was 2.8 cm, with an average R.E.N.A.L. score (Radius, tumour size as maximum diameter; Exophytic/endophytic properties of the tumour, Nearness of tumour deepest portion to the collecting system or sinus, Anterior, a/posterior, p, descriptor, and the Location relative to the polar line) of 6.8. The mean warm ischaemia time was 21 min and mean operative duration was 196 min. The mean estimated blood loss was 182 mL, with a 7.4% transfusion rate. The conversion rate was 1.7% and the postoperative complication rate was 14%. The mean length of stay was 3.6 days. There were positive surgical margins in 1.7% of patients. The mean decrease in renal function was 5.4% and the mean follow-up was 8.4 months. CONCLUSIONS: RPN is feasible and safe for different levels of complexity of renal tumours. Perioperative outcomes are comparable to those found with more established techniques. Future studies should compare different approaches and prioritise prospective and randomised designs. PMID- 26557999 TI - The development of robotic surgery in the Middle East. AB - OBJECTIVES: We provide an overview of the development of robotic surgery in the Middle East since its first introduction in April 2003 in the Kingdom of Saudi Arabia (KSA). METHODS: We searched MEDLINE using 20 keywords/phrases and identified 44 reports, of which only 15 were relevant. Five of these articles were duplicated when using two different keywords. Therefore, no more than 10 articles were found that were relevant to the scope of this review. RESULTS: After completing the MEDLINE search to identify articles related to robotic surgery in the Middle East, we noted that all of the nine case series (Level of evidence 3a) reported took place in the KSA, with no other reported series from other Middle-Eastern countries. To the best of our knowledge, there are no operating robotic surgery systems (da Vinci, Intuitive Surgical, CA, USA) in the Middle East other than in the KSA, Qatar and Egypt. The number of robotic surgery cases and newly adapted robotic procedures is increasing. Two major institutions in the KSA have expanded to robotic-assisted pyeloplasty in all of their cases since January 2005. CONCLUSION: There are 10 da Vinci robots in the KSA, with over 35 trained surgeons, yet very few index cases. The cancer incidence rate, lack of practitioners' referrals, and demographic age distribution are all factors that contribute significantly to the few index cases reported. By consolidating the robotic surgery procedures in high-volume speciality centres, hospitals can increase their case loads by promoting the multidisciplinary use of the robotic system. Even though growth is relatively slow, we believe that robotic surgery is gaining momentum, and its benefits and innovation will soon be grasped in other countries in the Middle East. PMID- 26558000 TI - Robot-assisted urological surgery: Current status and future perspectives. AB - OBJECTIVES: To discuss the current status of robot-assisted urological surgery. METHODS: We searched PubMed for articles published from 2008 using the search terms 'advances', 'robotic surgery equipment' and 'instrumentation'. We also searched PubMed for articles describing the latest developments in reconstructive techniques for lower and upper urinary tract procedures. Finally, we searched PubMed for original articles containing the terms 'robotic surgery training' and 'credentialing'. RESULTS: With each release of hardware or ancillary instrumentation, the reconstructive abilities of the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) improve. Recent developments in reconstructive capabilities of robotic urological surgery include posterior reconstruction during robot-assisted radical prostatectomy, barbed sutures for urethrovesical anastomosis, sliding-clip renorrhaphy for robot-assisted partial nephrectomy, and repair of pelvic organ prolapse. The safe implementation of robotic surgery is aided by new guidelines in credentialing and proctoring, and the introduction of virtual reality simulators for training. CONCLUSION: Robotic urological surgery is rapidly developing and expanding globally. To achieve the highest levels of safety for patients, surgeons must ensure that the implementation of robotic surgery is an integrative and effective process. PMID- 26558001 TI - Robotic radical prostatectomy: The new gold standard. AB - OBJECTIVES: Open radical prostatectomy (RP) has been the standard and primary treatment for focal prostate cancer. However, in recent years this view has changed, as robot-assisted laparoscopic RP has gained acceptance among urologists. In this review we evaluate the importance and place of robotics in laparoscopic urological surgery, discussing several techniques that are currently being used and potentially new techniques that might be used in the future. METHODS: We systematically reviewed papers published between 1998 and 2011 using the keywords 'robotic prostatectomy' 'gold standard' and the Medline database. In addition, after selecting relevant reports we searched 'related citations' of the documents to find further supporting published papers. RESULTS: In all, 50 original papers were identified using the search criteria; we also found 28 through 'related citations' browsing. Papers were selected according to their relevance to the current topic (i.e. RP, original articles) and incorporated into this review. These papers were used for their information on the advantages of using robotics, as well as innovative ideas being used in the field of robotic urological surgery. CONCLUSION: Almost a decade after the first robotic RP many reports show the benefits and advantages of incorporating robotics into urological surgery. Robotic surgery decreases the learning curve necessary for surgeons when compared with laparoscopic techniques. In addition, patients prefer robotics, as the procedure is less invasive, diminishes the duration of hospitalisation and speeds the return to function. PMID- 26558002 TI - Laparoscopic and robot-assisted surgery in the management of urinary lithiasis. AB - OBJECTIVES: To review the current role of laparoscopy and robot-assisted laparoscopy for managing urinary lithiasis. RESULTS: The contemporary indications for laparoscopic stone management are: anatomical variations in location or shape of the kidney (pelvic kidney, horseshoe kidney and malrotated kidney); coexisting pathologies, e.g. pelvi-ureteric junction obstruction; and stones in a renal unit with lower ureteric obstruction. The laparoscopic approach allows the simultaneous management of both the pathologies. Symptomatic stones in diverticula not amenable to endourological intervention can be treated with laparoscopy. Large impacted pelvic and ureteric calculi with a functioning renal unit are an indication for laparoscopic ureterolithotomy or pyelolithotomy. This review of current reports suggests that in a selected group of patients with complex stone disease the laparoscopic approach offers good success rates with minimal complications. There are few reports of robotic procedures in stone disease but existing data suggest that it is feasible. CONCLUSION: Laparoscopic surgery is effective for complex renal stones and offers excellent stone clearance rates with minimal morbidity. Laparoscopic surgery is complementary in managing these stones. Robot-assisted laparoscopic technique of urinary tract stone management is in its early stage of implementation and randomised trials that compare robot assisted outcomes with other minimally invasive techniques are needed. PMID- 26558003 TI - Laparoscopic radical cystectomy. AB - OBJECTIVE: Laparoscopic radical cystectomy (LRC) has emerged as a minimally invasive alternative to open radical cystectomy (ORC). This review focuses on patient selection criteria, technical aspects and postoperative outcomes of LRC. METHODS: Material for the review was obtained by a PubMed search over the last 10 years, using the keywords 'laparoscopic radical cystectomy' and 'laparoscopic bladder cancer' in human subjects. RESULTS: Twenty-two publications selected for relevance and content were used for this review from the total search yield. The level of evidence was IIb and III. LRC results in comparable short- and intermediate-range oncological outcomes to ORC, with generally longer operative times but decreased blood loss, postoperative pain and hospital stay. Overall operative and postoperative morbidity are equivalent. CONCLUSION: In experienced hands, LRC is an acceptable minimally invasive alternative to ORC in selected patients, with the main advantage of decreased blood loss and postoperative pain, as well as a shorter hospital stay and recovery. PMID- 26558004 TI - Laparoscopic donor nephrectomy: The Middle East experience. AB - OBJECTIVES: To summarize the experience of the Middle East in laparoscopic donor nephrectomy (LDN), to discuss the associated advantages and salient problems, to examine the learning curve encountered compared with that of the pioneering centres in the West, and the contribution of the regional centres to the worldwide experience. METHODS: We searched Medline and PubMed for all centres performing LDN in the Middle East. Questionnaires were e-mailed to the regional transplantation centres, and programme directors, and leading urological and transplant surgeons were contacted by telephone. RESULTS: LDN in the Middle East was first introduced in 2000; this approach has been pioneered and practised at seven transplant centres within five countries in the region, and was restricted to only three Arab countries, i.e. Lebanon, Egypt and Kuwait. Data collection yielded a total of 888 procedures over one decade, representing only 2% of the total of ~50,000 transplants during the same period. Despite variability of accurate reporting the overall outcomes were similar to those of open DN. The spectrum of complications was comparable to that from major centres in the USA during their learning curve. CONCLUSIONS: The introduction of LDN in the Middle East has been gratifying. The relative hesitancy in introducing LDN in the rest of the Arab Middle East is multifaceted. The advantages conferred to the donor underscore the need for further expansion of this approach for kidney retrieval. PMID- 26558005 TI - Laparoscopic adrenalectomy: An update. AB - OBJECTIVE: To review the current role and outcome of laparoscopic adrenalectomy (LA) in the management of adrenal tumours. METHODS: A Medline search using the keywords (adrenalectomy, laparoscopy, adrenal masses/tumours) was done for reports published between 1990 and 2011. Key articles were used to find more relevant references on the evaluation and laparoscopic management of adrenal masses. RESULTS: The hormonal evaluation is not standardised, but initial screening tests are recommended and followed with confirmatory ones when positive, equivocal or the clinical presentation suggest adrenal hyperfunction. The imaging studies had, and continued to, advance, especially computed tomography (CT), magnetic resonance imaging and positron-emission tomography/CT. These advances have increased the accuracy of the diagnosis of adrenal masses, with a reported high sensitivity and specificity of 95-100%. The introduction of laparoscopy has resulted in more adrenal lesions being removed, especially incidental lesions smaller than the 5-6 cm that was previously the indication for surgical excision. The technique has developed and larger lesions of >6 cm are now considered for LA in the proper setting. The transperitoneal and retroperitoneal approaches are currently widely practised, with minor differences in the outcome. The reported outcome, although mostly retrospective, is excellent and with fewer complications. The role of LA for adrenal malignancy should be considered cautiously. Preoperative imaging signs of invasion into surrounding structures should be considered a contraindication for LA. CONCLUSION: LA is the standard procedure for most adrenal lesions of appropriate size and no signs of surrounding tissue invasion, giving an excellent outcome. PMID- 26558006 TI - Laparoscopic retroperitoneal lymph node dissection for testicular cancer. AB - OBJECTIVES: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) was introduced over 20 years ago as a less invasive alternative to open node dissection. In this review we summarise the indications, surgical technique and outcomes of L-RPLND in the treatment of testicular cancer. METHODS: We searched MEDLINE using the terms 'laparoscopy', 'laparoscopic', 'retroperitoneal lymph node dissection', 'RPLND' and 'testicular neoplasms'. Articles were selected on the basis of their relevance, study design and content, with an emphasis on more recent data. RESULTS: We found 14 pertinent studies, which included >1300 patients who received either L-RPLND (515) or open RPLND (788). L-RPLND was associated with longer mean operative times (204 vs. 186 min), but shorter hospital stays (3.3 vs. 6.6 days) and lower complication rates (15.6% vs. 33%). Oncological outcomes were similar between L-RPLND and open RPLND, with local relapse rates of 1.3% and 1.4%, incidence of distal progression of 3.3% and 6.1%, biochemical failure in 0.9% and 1.1% and cure rates of 100% and 99.6%, respectively. CONCLUSION: There are no randomised controlled studies comparing L RPLND with open RPLND. A review of case and comparative series showed similar perioperative and oncological outcomes. Patients undergoing L-RPLND on average have shorter hospital stays, a quicker return to normal activity and improved cosmesis. PMID- 26558007 TI - The evolving role of laparoscopic surgery in paediatric urology. AB - OBJECTIVES: We review the various applications of laparoscopic and robotic assisted laparoscopy in paediatric urology, as the laparoscopic and robotic approach in this population is gradually being recognised. METHODS: We searched PubMed for human studies in English that were published between 1990 and the present, focusing on laparoscopic nephrectomies and partial nephrectomies, laparoscopic and robotic pyeloplasties and ureteric reimplantation, laparoscopic orchidopexy and varicocelectomy. We also reviewed robotic-assisted laparoscopic urological major reconstructions. Key articles were reviewed, extracting the indications, techniques, and the advantages and disadvantages. RESULTS AND CONCLUSIONS: Laparoscopy has a defined place in modern paediatric urological surgery. Laparoscopic nephrectomies, pyeloplasties and abdominal exploration for the evaluation and management of impalpable undescended testicles have become the standard of care. Robotic-assisted laparoscopic surgery is developing as a safe and effective option even for infant patients. PMID- 26558008 TI - Surgical complications of laparoscopic urological surgery. AB - OBJECTIVES: To describe the incidence, identification and management of common intraoperative complications, including vascular, urological, bowel and visceral complications, of laparoscopic urological surgery. METHODS: We searched the databases of PubMed and Medline for relevant English language reports, using the keywords 'laparoscopy', 'urologic' and 'complication'. RESULTS: The search yielded 967 papers in all, and a review of these yielded a total of 42 relevant papers. CONCLUSION: Despite its advantages, laparoscopic urological surgery is associated with complications having rates as high as 22%. As surgical volumes increase, the incidence and magnitude of complications have increased progressively. Meticulous surgical technique, surgeon experience, and a high degree of suspicion are necessary throughout the surgical endeavour. The intraoperative recognition and management of complications is mandatory. PMID- 26558009 TI - Laparoendoscopic single-site surgery in urology: Evaluation of complications. AB - OBJECTIVE: To comprehensively review current reports on the complications of laparoendoscopic single-site surgery (LESS), introduced recently into urology as an option for treating various urological pathologies. METHODS: We reviewed previous reports to August 2011 using Medline, focusing on LESS in urology, with special interest in the complications, evaluating those during and after surgery, as well as conversions to reduced-port laparoscopy, conventional laparoscopy and open surgery. RESULTS: There are increasing reports of LESS in urology, with expanding indications. Complication rates both during and after surgery are low and related mostly to the technical difficulty and dexterity with the currently available instruments. Overall, intraoperative complications were reported by 11 published studies, while postoperative complications were reported by 15. Although the overall conversion rates to open surgery and conventional laparoscopy were low, the incidence of reduced-port laparoscopy was significantly higher. CONCLUSIONS: Although there are expanding indications for LESS in urology, the risk of complications is low. This might be related to the fact that LESS is still restricted to experienced laparoscopic surgeons, and to the criteria for selecting patients. PMID- 26558010 TI - Erectile dysfunction in Arab countries. Part I: Prevalence and correlates. AB - OBJECTIVE: To review the contemporary knowledge of local investigations in the Arab countries that were conducted to identify the magnitude of erectile dysfunction (ED) and its correlates among men in this region. METHODS: MEDLINE was reviewed for English-language reports from 2000 to 2011 for Arab countries, using the terms 'erectile dysfunction' and 'prevalence'. RESULTS: In all, 102 articles were found to be relevant to the review. Unfortunately only a few had a high level of evidence and the remaining studies were not controlled in their design. Several local studies showed that the prevalence of ED was >40% among Arab men. Risk factors and medical comorbidities that negatively affect the cardiovascular system, endothelial function and ultimately erectile function were common in men in Arab countries. For instance, at least five Arab countries are included in the top 10 countries worldwide with a high prevalence of diabetes mellitus. The global statistics showed that other risk factors such as obesity, smoking, hypertension and dyslipidaemia are also very prevalent in Arab countries. This fact can explain the high incidence of both cardiovascular disease and ED among Arab men. CONCLUSION: ED is very prevalent among Arab men. Arab countries are among those with the highest prevalence of endothelial dysfunction risk factors, which could explain this high prevalence of ED. PMID- 26558011 TI - Erectile dysfunction in Arab countries. Part II: Diagnosis and treatment. AB - OBJECTIVE: To review local published data on the diagnosis and treatment of erectile dysfunction (ED) in Arab countries. METHODS: MEDLINE was searched for English-language articles published from 2000 to 2011, using the search terms 'Arab countries', 'sexual dysfunction', 'diagnosis' and 'treatment'. RESULTS: In all, 86 articles were found to be relevant to this review; only a few had a high level of evidence and the remaining studies used an uncontrolled design. Several local studies were consistent with previous reports showing that a customised diagnostic pathway, with full consideration of the patient's goals, is adopted by most clinicians to treat ED. For an effective treatment, the evaluation methods should answer important questions about the aetiology and severity of ED, as well as the patient's and partner's goals and expectations. As ED is known to be associated with many common medical comorbidities and medications, careful questioning can yield information about peripheral vascular disease, coronary artery disease, diabetes, hypertension, dyslipidaemia, and tobacco and alcohol use. The presence of psychological, neurological or chronic debilitating diseases can direct further evaluation. CONCLUSION: The methods used for the diagnosis and treatment of ED need more investigation, especially in Arab countries. Only a few studies addressed the results of different methods of investigating and treating ED among Arab men. PMID- 26558012 TI - Prognostic markers in renal cell carcinoma: A focus on the 'mammalian target of rapamycin' pathway. AB - OBJECTIVES: Increased knowledge about the molecular pathways involved in tumorigenesis has led to the discovery of new prognostic molecular markers and development of novel targeted therapies for renal cell carcinoma (RCC). In this review we describe the prognostic markers of RCC and highlight the areas of recent discovery with a focus on the mammalian target of rapamycin (mTOR) pathway. METHODS: We reviewed previous reports, using PubMed with the search terms 'renal cell carcinoma', 'molecular markers', 'prognosis', 'outcomes' and 'mammalian target of rapamycin pathway' published in the last two decades. We created a library of 100 references and focused on presenting the recent advances in the field. RESULTS: Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC. Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC. There is a demand to integrate clinical, pathological and molecular markers into accurate prognostic models to provide patients with the most personalised cancer care possible. CONCLUSIONS: The mTOR pathway is highly implicated in RCC tumorigenesis and progression, and its constituents might represent a promising prognostic tool and target for treating RCC. Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC. PMID- 26558013 TI - Versatility of the ventral approach in bulbar urethroplasty using dorsal, ventral or dorsal plus ventral oral grafts. AB - OBJECTIVES: To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. PATIENTS AND METHODS: Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2 cm, range 1.5-5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture 3.7, range 1.5-8) a ventral graft urethroplasty (VGU), and 63 (29.2%; mean stricture 3.4, range 1.5-10) a dorsal plus ventral graft urethroplasty (DVGU). The strictured urethra was opened by a ventral sagittal urethrotomy and BM graft was inserted dorsally or ventrally or dorsal plus ventral to augment the urethral plate. RESULTS: The median follow-up was 37 months. The overall 5-year actuarial success rate was 91.4%. The 5-year actuarial success rates were 87.8%, 95.5% and 86.3% for the DGU, VGU and DVGU, respectively. There were no statistically significant differences among the three groups. Success rates decreased significantly only with a stricture length of >4 cm. CONCLUSIONS: In BM graft bulbar urethroplasties the ventral urethrotomy access is simple and versatile, allowing an intraoperative choice of dorsal, ventral or combined dorsal and ventral grafting, with comparable success rates. PMID- 26558014 TI - Does the afferent tubular segment in an orthotopic bladder substitution compromise ureteric antireflux properties? An experimental study in dogs. AB - OBJECTIVE: To study the effects of a short ureter on renal function and histology in an orthotopic bladder substitution model using a long afferent limb, in a canine model. MATERIALS AND METHODS: The study included nine adult mongrel dogs. A 40-cm segment of ileum was isolated, the distal half detubularized, configured into a U-shape and sutured to form a flat plate; this was then used to augment the bladder. The proximal half of the isolated ileum remained in continuity with the enterocystoplasty to form an isoperistaltic ileal 'chimney'. The left ureter was divided at its lumbar part and anastomosed to the chimney using a refluxing end-to-side Nesbit technique. The contralateral ureter was divided at its lower end and then anastomosed directly to the augmented segment of the bladder in a similarly refluxing manner to act as a control. The assessment after surgery included biochemical studies, ascending cystography, intravenous urography (IVU) and radioisotope renography at 6 weeks. The last two methods were repeated at intervals of 3 and 6 months after surgery. Urine culture was obtained and both kidneys were examined histopathologically at 6 months. RESULTS: The biochemical values assessed in all dogs were comparable to those before surgery. The urine culture obtained from the augmented bladders showed significant bacterial growth in all dogs. IVU at all follow-up sample times showed a normal configuration of both kidneys. Ascending cystography showed reflux in four of nine dogs on the right and six on the left side. There was a progressive decrease in the mean selective renographic clearance values of each of the right and left kidneys at intervals of 6 weeks, 3 and 6 months. The mean percentage reduction of renographic clearance was significantly higher in the left kidneys at 6 weeks and 3 months. Histopathological examination showed evidence of interstitial nephritis in all nine dogs and pyelonephritis in four of the left kidneys, while none of the right kidneys showed evidence of inflammation. CONCLUSION: Adequate peristalsis in a healthy long ureter is superior to the ileal segment substitution for protecting the kidney tissue against inflammation in the absence of an anatomical antireflux mechanism. PMID- 26558015 TI - Recurrence pattern in patients with locally advanced renal cell carcinoma: The implications of clinicopathological variables. AB - OBJECTIVES: Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high. To date the predictors of recurrence in those patients remain controversial. The aim of the present study was to assess the relapse pattern in those patients and identify predictors for recurrence. PATIENTS AND METHODS: We evaluated retrospectively 112 consecutive patients who underwent surgery for LARCC (T3-T4N0M0) between January 2000 and December 2010. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database. Studied variables were age, mode of presentation, Tumour-Node-Metastasis (TNM) stage, Fuhrman nuclear grade, histological subtype, tumour size, venous thrombus level, collecting-system invasion and sarcomatoid differentiation. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted. RESULTS: Patients were followed for a mean and median follow-up of 33 and 24 months, respectively, after surgery. During the follow-up, recurrences (distant and/or local) were recorded in 58 patients, representing 52% of the cohort. The mean and median times to recurrence were 25 and 13 months, respectively. Sites of recurrence were multiple in 36 patients (62%), lung only in 14 (24%), and local in eight (14%). RFS rates at 1, 2, and 5 years were 50%, 43% and 34%, respectively, while the median RFS was 23.7 months. Using univariate analysis, RFS after nephrectomy was significantly shorter in patients aged <70 years, symptomatic at presentation, with larger tumours, higher nuclear grade, collecting-system invasion, and/or sarcomatoid differentiation. After multivariate analysis, T-stage, nuclear grade and sarcomatoid differentiation retained their power as independent predictors of RFS (P = 0.032, <0.001 and 0.003, respectively). CONCLUSIONS: For patients with LARCC, T-stage, grade and sarcomatoid differentiation independently dictate the risk of tumour recurrence. Considering these variables in the postoperative surveillance protocols and in the need for a multimodal therapeutic approach is highly recommended. PMID- 26558016 TI - Accuracy of photodynamic diagnosis in the detection and follow-up of patients with upper urinary tract lesions: Initial 3-year experience. AB - OBJECTIVE: To assess the diagnostic accuracy of photodynamic diagnostic (PDD) ureterorenoscopy for detecting upper-urinary tract transitional cell carcinoma (UUT-TCC) in our initial 3 years, and compare the results with that of white light ureterorenoscopy (WLU). PATIENTS AND METHODS: Between August 2007 and March 2010, 32 patients underwent PDD flexible ureterorenoscopy for UUT-TCC. Oral 5 aminolaevulinic acid (5-ALA) was used as the photosensitiser. The sensitivity, specificity and detection rate of PDD were calculated. RESULTS: The sensitivity, specificity, positive and negative predictive values of PDD for detecting abnormal tissue were 96%, 100%, 100% and 88%, compared to the results of WLU of 80%, 86%, 95% and 55%, respectively. PDD was able to detect 96% (24/25) of the abnormal tissue and 96% (21/22) of cancerous tissue, while WLU detected 80% (20/25) of abnormal tissue and 91% (20/22) of the tumour tissue. Three patients of the 32 (10%) developed side-effects related to 5-ALA; two patients developed a facial-skin photosensitive reaction and one developed hypotension. All were treated conservatively, with no long-term effects. CONCLUSION: PDD can be used safely in the UUT, and with a higher sensitivity, specificity and detection rate than standard WLU for detecting UUT tumours. PMID- 26558017 TI - Flank free modified supine position: A new modification for supine percutaneous nephrolithotomy. AB - OBJECTIVES: Percutaneous nephrolithotomy (PCNL) is the standard management for large and/or complex urolithiasis, but the standard patient position for PCNL is undecided. With the patient prone PCNL has several drawbacks, while when supine, as described previously, PCNL has mechanical limitations. We describe a modification that aims to overcome these limitations and provide easy access comparable to that in the prone position. PATIENTS AND METHODS: This prospective study was carried out at the Urology Department, Zagazig University, Egypt, from October 2008 to March 2011, and included 78 patients (48 men and 30 women). First the patient was placed supine and then in the 'flank-free modified' supine position. The distance between the last rib and the iliac crest in the posterior axillary line was measured in both positions. RESULTS: The mean age of the patients was 40.8 years, the mean (SD) stone diameter was 3.4 (0.7) cm, the number of right/left stones was 34/44, and mean body mass index was 28.8 kg/m(2). The mean (SD) increase in the distance between the last rib and the iliac crest in the posterior axillary line in the flank free modified supine position vs. the previous supine position was 12 (0.8) mm. CONCLUSION: The flank-free modified supine position increases the distance between the last rib and the iliac crest, and, together with the absence of a cushion under the flank, provides ample space for puncture, dilatation, multiple tracts and manoeuvrability of the system with the nephroscope. PMID- 26558018 TI - Has the significance of incidental findings on unenhanced computed tomography for urolithiasis been overestimated? A retrospective review of over 800 patients. AB - OBJECTIVES: To evaluate the detection of clinically unsuspected pathologies using 64-slice multidetector computed tomography (CT) of the abdomen in patients with flank pain. The presence of significant incidental findings (those warranting immediate management) was also correlated with that of urolithiasis, to assess potential changes of management. PATIENTS AND METHODS: The study included 899 patients undergoing CT in a 6-month period between June and December 2008. Patients who were referred from outside, with no medical record in the hospital where the study was conducted, and those who were lost to follow-up, were excluded. All of the CT examinations were reported after a radiology resident and a consultant radiologist with >4 years of experience evaluated the CT. Genitourinary and extra-genitourinary findings were assessed and divided into clinically significant or not. RESULTS: The overall incidence of additional and incidental findings was 14%. Besides urolithiasis and obstruction there were 34 (28%) genitourinary findings and 87 (72%) extra-genitourinary findings; most of the former were insignificant. Of the extra-genitourinary findings, significant diagnoses were documented in 34 cases. CONCLUSIONS: Abdominal multidetector CT detects more incidental findings which are clinically significant. PMID- 26558019 TI - Vascular and haemorrhagic complications of adult and paediatric live-donor renal transplantation: A single-centre study with a long-term follow-up. AB - OBJECTIVES: To compare the haemorrhagic and vascular complications between paediatric and adult renal transplant recipients with a long-term follow-up. PATIENTS AND METHODS: Between March 1976 and December 2006, in all, 1865 live donor renal transplants were carried out. Patients were stratified according to their ages into two groups; paediatric (?18 years; 259) and adult (>18 years; 1606). Variables assessed included incidence, risk factors, management and sequelae of vascular and haemorrhagic complications. The effect of these complications on patient and graft survival was compared. RESULTS: Haemorrhage requiring active intervention (percutaneous drainage or surgical exploration) was reported in seven children (2.7%) and 29 adults (1.8%), while thrombotic or stenotic complications were recorded in two children (0.77%) and 19 adults (1.18%; P < 0.05). Female gender, delayed onset of diuresis and acute tubular necrosis were significant predictors of vascular complications on univariate analysis, but none remained significant on multivariate analysis. In adults, vascular complications had a significant negative effect on mean (SD) 10-year graft survival compared to patients with no complications, at 19.8 (7.63)% vs. 55.7 (1.66)% (P = 0.01). Children who developed vascular complications had a significantly higher 5- and 10-year graft survival rate than adults (P = 0.01). CONCLUSION: The incidence of vascular complications is comparable in paediatric and adult transplants. Vascular complications had a significant negative influence on graft survival in adult recipients. Children who developed vascular complications appear to tolerate its effects and have a better graft survival than have adults. PMID- 26558020 TI - Urinary tract infection in renal transplantation. AB - INTRODUCTION: Urinary tract infection (UTI), especially recurrent UTI, is a common problem, occurring in >75% of kidney transplant (KTX) recipients. UTI degrades the health-related quality of life and can impair graft function, potentially reducing graft and patient survival. As urologists are often involved in treating UTI after KTX, previous reports were searched to elucidate underlying causes, risk factors and treatment options, as well as recommendations for prophylaxis of UTI after KTX. METHODS: Pubmed/Medline was searched and international guidelines and recommendations for prevention and treatment of UTI after KTX were also assessed. RESULTS: Most studies on UTI after KTX have a small sample, and are descriptive and retrospective. Many transplant- and recipient related risk factors have been identified. While asymptomatic bacteriuria is often treated, even though some studies advise against it, symptomatic UTI should be treated empirically after collecting urine for microbiological analysis, to avoid the development of transplant pyelonephritis with a high chance of urosepsis. The duration of treatment has not been determined in studies and recommendations refer to the treatment of complicated UTI in the non-transplant population. Prophylaxis has not been the focus of studies either. CONCLUSION: UTI after KTX is still largely an under-represented field of study, despite many recipients developing UTI after KTX. Prospective studies on this topic are urgently needed. PMID- 26558021 TI - The over-exaggerated chronic nephrotoxicity of calcineurin inhibitors. AB - BACKGROUND: Late kidney allograft failure remains a major problem in kidney transplantation. While there is no doubt that acute nephrotoxicity from calcineurin inhibitors (CNIs) exists, chronic CNI nephrotoxicity has been the subject of much debate in the transplant community. METHODS: We identified original articles related to the use of CNIs in renal and extra-renal solid-organ transplantation, to examine the available evidence about their chronic nephrotoxicity. RESULTS: There is clearly a lack of firm evidence for the role of CNIs as a major injurious agent causing chronic renal dysfunction and allograft failure. Moreover, recent evidence shows that the pathological lesions typically linked to chronic CNI use are not specific. A growing body of evidence shows that alloimmunity is a much more important cause of late renal allograft failure. CONCLUSIONS: More research should focus on addressing the true causes of chronic graft dysfunction rather than continuing to propagate the exaggerated contribution of CNIs to late graft loss. PMID- 26558022 TI - Pregnancy in renal transplantation: Recipient and donor aspects in the Arab world. AB - OBJECTIVE: There are many kidney transplant recipients and living donors of reproductive age, and the prevalence of pregnancies in kidney transplant recipients can reach 55% in the Middle Eastern countries. Living kidney donation is predominant in this region. As the risks and outcomes of pregnancy should be a part of counselling for both recipients and donors, we reviewed available reports on maternal and foetal outcomes in these particular populations. METHODS: Information was obtained from retrospective analyses of a large database, and from single-centre reports indexed in PubMed on pregnancy in donors and kidney transplant recipients. The keywords used for the search included 'fertility', 'kidney disease', 'pregnancy', 'maternal/foetal outcomes', 'kidney transplant recipient', 'immunosuppression side-effects', 'living donor' and 'Arab countries'. RESULTS: Pregnancies in kidney transplant recipients are most successful in those with adequate kidney function and controlled comorbidities. Similarly to other regions, pregnant recipients in the Middle East had a higher risk of pre-eclampsia (26%) and gestational diabetes (7%) than in the general population. Caesarean section was quite common, with an incidence rate of 61%, and the incidence of pre-term birth reached 46%. CONCLUSIONS: Most living donors can have successful pregnancies and should not be routinely discouraged. Women who had pregnancies before and after donation were more likely to have adverse maternal outcomes (gestational diabetes, hypertension, proteinuria, and pre eclampsia) in the latter, but no adverse foetal outcomes were found after donation. The evaluation before donation should include a gestational history and counselling about the potential risks. PMID- 26558023 TI - Transobturator vaginal tape (inside-out) for stress urinary incontinence after radical cystectomy and orthotopic reconstruction in women. AB - OBJECTIVES: To evaluate the safety and clinical efficacy of the transobturator vaginal tape 'inside-out' (TVT-O) procedure for managing new-onset stress urinary incontinence (SUI) after radical cystectomy (RC) and orthotopic W-neobladder construction in women. PATIENTS AND METHODS: Between January 2004 and June 2010, 57 women were treated with RC and orthotopic ileal neobladder reconstruction. Six of these patients (median age 44 years, range 39-62; grade 2 muscle-invasive squamous cell carcinoma in four and transitional cell carcinoma in two) developed de novo SUI that was moderate in four and severe in two. The median (range) duration of SUI was 11 (9-18) months. All six patients underwent TVT-O for control of their SUI. RESULTS: Four patients were completely dry day and night (three of them can initiate voiding and one cannot, and uses intermittent catheterization). One patient improved, as assessed by using fewer pads (from 5-7 pads to 1 pad/day and night). She can initiate voiding but has minimal leakage only on moderate exertion. One patient who had severe SUI showed no improvement. Patients were followed for a mean (range) of 18 (17-32) months, with no deterioration in the continence status. CONCLUSION: These encouraging results confirm the safety and clinical efficacy of TVT-O for managing new-onset SUI after RC and ileal neobladder construction, although a larger survey and a longer follow-up are needed. PMID- 26558024 TI - The value of measuring the prostatic resistive index vs. pressure-flow studies in the diagnosis of bladder outlet obstruction caused by benign prostatic hyperplasia. AB - OBJECTIVE: To compare the prostatic resistive index (RI) and measurements from pressure-flow studies (PFS) for the diagnosis and follow-up of bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 338 men (aged 55-82 years) presenting with lower urinary tract symptoms were evaluated prospectively for BOO secondary to BPH. In all patients, the prostatic RI was measured by transrectal power Doppler ultrasonography. PFS were assessed in all patients and depending on the results the patients were divided into an obstructive and an unobstructive group. The receiver operating characteristic (ROC) curve was used to determine the prostatic RI threshold value for predicting BOO secondary to BPH. Patients who were confirmed to have BOO secondary to BPH received either medical or surgical treatment, and they were re-evaluated after 3 and 6 months with prostatic RI measurements. RESULTS: According to the PFS the obstructive group included 158 patients and the unobstructive group 180 patients. The mean (SD) prostatic RI was significantly higher in the obstructive group, at 0.73 (0.04), than in the unobstructive group, 0.65 (0.05) (P < 0.001). Using the ROC curve a prostatic RI of ? 0.71 predicted BOO secondary to BPH, with 84.6% sensitivity, 78.4% specificity and 83.8% overall predictability. After management, the prostatic RI of the obstructive group, 0.69 (0.08), was significantly lower than before treatment, 0.73 (0.04) (P < 0.05). CONCLUSIONS: The prostatic RI can predict BOO with high specificity and sensitivity. We believe that the prostatic RI could be a useful variable for the diagnosis and follow-up of patients with BPH. PMID- 26558025 TI - Cell-seeded tubular acellular matrix for replacing a long circumferential urethral defect in a canine model: Is it clinically applicable? AB - OBJECTIVE: To evaluate the feasibility of replacing a relatively long segment of the canine urethra by a tube of cell-seeded acellular collagen bladder matrix. MATERIALS AND METHODS: The study included 14 female mongrel dogs in which a 3-cm segment of the whole urethral circumference was excised and replaced by a tube of acellular matrix seeded with autologous urothelial cells. The acellular matrix was obtained from the excised bladder of female donor dogs that were not included in the study. Autologous cells were obtained from the study dogs by open bladder biopsy, with subsequent in vitro expansion and cultivation. Urethroplasty was performed over a 16 F urethral catheter that was kept for 4 weeks. The dogs were killed humanely (one every week for 4 weeks and then one monthly for 10 months). After stent removal, retrograde urethrography was used each month in the living dogs. If retention occurred a urethrogram was taken and then the dog was killed humanely. All grafts from dogs were harvested and sent for histopathological examination. RESULTS: Exploration at 1, 2, 3 and 4 weeks showed progressive shrinkage in length, together with relative narrowing of the lumen. Three dogs developed retention within a week after stent removal and the other seven developed retention within 4 months. Retrograde urethrograms showed evidence of stricture and/or fistula at the graft site in all dogs. On exploration, grafts showed marked shrinkage (0.6-1.2 cm in length) with complete obliteration of their lumens. Histopathological examination showed extensive fibrosis of the matrix with no evident urothelial architecture. CONCLUSION: Cell-seeded acellular matrix tube is insufficient to replace a 3-cm circumferential urethral defect in dogs. PMID- 26558026 TI - Renoprotection against complete unilateral ureteric obstruction: Is there an ultimate choice? AB - OBJECTIVES: To evaluate and compare the relative contribution of different therapeutic agents for renoprotection against complete unilateral ureteric obstruction (UUO), using a rabbit model sampled at different times. MATERIALS AND METHODS: Eighty-four male New Zealand White rabbits were divided into seven groups of 12 rabbits; a sham group, a control (left UUO + no medication) or left UUO and treated with either enalapril, losartan, verapamil, l-arginine or antioxidant (vitamin E and selenium mixture). Rabbits in the control and treated groups were subjected to 3, 10 and 21 days of complete ureteric ligation and then killed humanely. The control and treated groups were evaluated at baseline and at the end of the experiment, by measuring split effective renal plasma flow (ERPF) using diuretic renography, and the split glomerular filtration rate (GFR) using selective creatinine clearance. Renal histopathology was evaluated using a tubulo interstitial damage score. RESULTS: In the sham group there was no significant effect on any of the evaluated variables. For split ERPF, losartan showed the highest renoprotective effect, saving 44% and 77% of ERPF at 3 and 21 days after UUO, respectively. Losartan was also the best renoprotective agent for GFR. For renal histopathology, enalapril showed the earliest and greatest improvement as assessed by the damage score, reaching 60% at 21 days after UUO. l-Arginine was the next best effect to blockade the renin-angiotensin system for renoprotection. CONCLUSION: We suggest that blockade of the renin-angiotensin system provides the best renoprotection against the effects of complete UUO. PMID- 26558028 TI - Urinary stone disease: Great progress with promise for the future. PMID- 26558027 TI - Inhibitory effects of the ATP-sensitive potassium channel openers cromakalim, pinacidil and minoxidil on the carbachol-response curve in porcine detrusor muscle. AB - AIMS: ATP-sensitive potassium channels represent promising drug targets for treating specific bladder diseases. The inhibitory effects of ATP-selective potassium channel openers (PCOs) on the carbachol-response curve in porcine detrusor muscle were examined. MATERIALS AND METHODS: Each of the three substances used in the study represent one prototype of a different class of PCO: cromakalim belongs to the benzopyran series, pinacidil is a cyanoguanidine derivative, and minoxidil represents a pyrimidine derivative. The porcine detrusor muscle represents one of the best models for human detrusor. Experiments were conducted on muscle strips of porcine detrusor muscle suspended in a tissue bath. Concentration-response curves of carbachol were constructed after pretreatment with cromakalim at 10(-7), 10(-6) and 10(-5) M, and with pinacidil and minoxidil at 10(-6), 10(-5.5) and 10(-5) M, respectively. Each muscle strip was only used to examine one concentration of one substance. RESULTS: Cromakalim had the greatest inhibitory effect, significantly suppressing the carbachol response curve at 10(-6) and 10(-5) M. Pinacidil showed a significant inhibitory effect at 10(-5.5) and 10(-5) M, which was smaller than that of cromakalim. Minoxidil did not significantly inhibit the contractions at all examined concentrations. CONCLUSIONS: The examined ATP-sensitive PCOs belonging to the benzopyrans and cyanoguanidines significantly suppressed detrusor contractions. The development of derivatives of these prototypes could open new possibilities for the pharmacological treatment of selected bladder diseases. PMID- 26558029 TI - It is time to look at stone disease in a holistic way. PMID- 26558030 TI - The training of a 'stone doctor'. AB - OBJECTIVE: To propose alternative models of training for doctors treating patients with stones, and to identify their relative value, as such doctors are trained through urology programmes which sometimes cannot be expanded to meet the need, are short of teachers, too comprehensive and lengthy. This review explores new pathways for training to provide competence in the care of patients with stones. METHODS: Previous reports were identified and existing training models collectively categorised as Model 1. Three alternative models were constructed and compared in the context of advantages, acceptability, feasibility, educational impact and applicability in different geosocio-political contexts. RESULTS: In Model 2, urological and stone training diverge as options after common basic courses and experience. In Model 3, individuals access training through a common educational matrix (EM) for nurses, physicians, etc., according to the match between their capacities, entry requirements, personal desires and willingness for further responsibility. Stone doctors with no urological background cannot fulfil other service and educational commitments, and might create unwelcome dependence on other colleagues for complex situations. Programmes involving a common EM affect professional boundaries and are not easily acceptable. There is a lack of clarity on methods for medical certification and re-certification. However, the lack of technically competent stone experts in developing worlds requires an exploration of alternative models of training and practice. CONCLUSIONS: The ability to provide exemplary care after abbreviated training makes alternative models attractive. Worldwide debate, further exploration and pilot implementation are required, perhaps first in the developing world, in which much of the 'stone belt' exists. PMID- 26558031 TI - Stones in cats and dogs: What can be learnt from them? AB - OBJECTIVE: To review the clinical features of stone disease in dogs and cats for a non-veterinary audience. METHODS: Relevant peer-reviewed scientific reports were reviewed. RESULTS: Lower urinary tract stones are more common in dogs and cats than they are in humans. In addition to struvite stones, calcium oxalate, urate and cystine stones are all commonly found in the bladder and the urethra. The genetic basis for stone disease in some breeds of dog has been elucidated. The small size of cats creates technical challenges when managing ureterolithiasis. CONCLUSIONS: Naturally occurring stone disease in companion animals is a valuable area for further study. The structure of the canine genome might facilitate the identification of novel disease loci in breeds of dog predisposed to stone formation. PMID- 26558032 TI - Metaphylaxis, diet and lifestyle in stone disease. AB - OBJECTIVE: The most common urinary stones (calcium salts, uric acid) form due to genetic factors and lifestyle. This review describes why, if and how medication and lifestyle changes can reduce the risk of formation. METHODS: Previous reports were reviewed to obtain information on three aspects of urolithiasis, i.e. epidemiology, mechanisms linking lifestyle and urolithiasis and lifestyle intervention for preventing urolithiasis. RESULTS: Epidemiological evidence links the prevalence of urinary stone formation to general lifestyle factors. Detailed analysis has identified individual lifestyle elements that affect the risk of urinary stone formation. Currently there are several concepts that explain the mechanism of stone formation. Urinary markers like calcium, oxalate, phosphate, uric acid and urinary pH are involved in all these concepts. Many studies show that changing (combinations of) specific lifestyle elements has a favourable effect on these urinary markers. Based on this evidence, protocols have been developed that use a combination of these lifestyle changes and medication to prevent stone formation. In well-controlled studies where patients are optimally informed and continuously motivated, these protocols clearly reduce the stone formation rate. In general practice the result is less clear, because the time and tools are insufficient to maintain long-term patient compliance in the use of medication and lifestyle advice. CONCLUSION: The risk of stone formation can be reduced in general practice when the patient's compliance is optimised by providing individualised advice, continuous information, and feedback and incorporation of the advice into a regular lifestyle. The use of 'e-tools' might enable this without increasing the time required from the physician. PMID- 26558033 TI - Methods for diagnosing the risk factors of stone formation. AB - OBJECTIVE: To compare various systems for assessing the risk of recurrent stones, based on the composition of urine. METHODS: The relative supersaturation (RSS) of urine, the Tiselius Indices, the Robertson Risk Factor Algorithms (RRFA) and the BONN-Risk Index were compared in terms of the numbers of variables required to be measured, the ease of use of the system and the value of the information obtained. RESULTS: The RSS methods require up to 14 analyses in every urine sample but measure the RSS of all the main constituents of kidney stones. The Tiselius Indices and the RRFA require only seven analyses. The Tiselius Indices yield information on the crystallisation potentials (CP) of calcium oxalate and calcium phosphate; the RRFA also provide information on the CP of uric acid. Both methods provide details on the particular urinary abnormalities that lead to the abnormal CP of that urine. The BONN-Risk Index requires two measurements in each urine sample but only provides information on the CP of calcium oxalate. Additional measurements in urine have to be made to identify the cause of any abnormality. CONCLUSIONS: The methods that are based on measuring RSS are work intensive and unsuitable for the routine screening of patients. The Tiselius Indices and the RRFA are equally good at predicting the risk of a patient forming further stones. The BONN-Risk Index provides no additional information about the causative factors for any abnormality detected. PMID- 26558034 TI - Metabolic syndrome, obesity and kidney stones. AB - OBJECTIVES: To give a comprehensive and focused overview on the current knowledge of the causal relations of metabolic syndrome and/or central obesity with kidney stone formation. METHODS: Previous reports were reviewed using PubMed, with a strict focus on the keywords (single or combinations thereof): urolithiasis, nephrolithiasis, kidney stones, obesity, metabolic syndrome, bariatric surgery, calcium oxalate stones, hyperoxaluria, insulin resistance, uric acid stones, acid base metabolism. RESULTS: Obesity (a body mass index, BMI, of >30 kg/m(2)) affects 10-27% of men and up to 38% of women in European countries. Worldwide, >300 million people are estimated to be obese. Epidemiologically, a greater BMI, greater weight, larger waist circumference and major weight gain are independently associated with an increased risk of renal stone formation, both for calcium oxalate and uric acid stone disease. CONCLUSIONS: There are two distinct metabolic conditions accounting for kidney stone formation in patients with metabolic syndrome/central obesity. (i) Abdominal obesity predisposes to insulin resistance, which at the renal level causes reduced urinary ammonium excretion and thus a low urinary pH; the consequence is a greater risk of uric acid stone formation. (ii) Bariatric surgery, the only intervention that facilitates significant weight loss in morbidly obese people, carries a greater risk of calcium oxalate nephrolithiasis. The underlying pathophysiological mechanisms are profound enteric hyperoxaluria due to intestinal binding of calcium by malabsorbed fatty acids, and severe hypocitraturia due to soft or watery stools, which lead to chronic bicarbonate losses and intracellular metabolic acidosis. PMID- 26558035 TI - Stone formation in the Middle Eastern Gulf States: A review. AB - OBJECTIVES: To review the possible causes of the high incidence of urolithiasis in the oil-rich Gulf States. METHODS: Data were extracted from published reports on the incidence of urolithiasis, affluence and diet in the Gulf States, various Western countries and China. RESULTS: There are strong relationships: (a) between the life-expectancy of stones in men and the Gross National Income (GNI) per capita of these countries; and (b) between the daily consumption of animal protein and GNI per capita. Together these data suggest that the occurrence of stones is proportional to the intake of animal protein, although they also indicate that there are additional factors that further increase the risk of urolithiasis in the populations of the Gulf. The consumption of oxalate in the Gulf is three times higher and that of calcium a half of what it is in Western countries. Thus, the average oxalate/calcium ratio in the intestines of the Gulf populations is five to six times higher than that in Western populations, leading to enteric hyperoxaluria and an increased risk of calcium-oxalate stone formation. The risk is further accentuated by the lower urine volumes, due to the hot, dry climate of the region, and lower excretions of citrate, from the highly acidic urine resulting from the high intake of animal protein. There is a high incidence of uric acid-containing stones from the acidic urine and the hyperuricosuria caused by the high intake of purine. CONCLUSIONS: The high incidence of urolithiasis in the Gulf is due to an adverse combination of dietary and environmental factors. PMID- 26558036 TI - Economics of stone disease/treatment. AB - OBJECTIVES: Urolithiasis is a considerable economic burden for health systems, especially in industrialised countries where the incidence of stone disease has increased during the last few decades, and probably will further increase for several reasons. METHODS: The survey was based on investigations in collaboration with a German health insurance company and on a literature search (PubMed, and the author's collection of proceedings of urolithiasis conferences: The keywords included economics, cost, urolithiasis, nephrolithiasis, renal stone disease, metaphylaxis, recurrence) during 1999-2011. In all, 1221 articles were found but only those cited here were sufficient for the purpose of the study. Due to the nature of the subject it is not possible to give levels of evidence, as economic data on stone treatment cannot be obtained with randomised studies. RESULTS: The costs for the treatment and diagnosis of stones vary tremendously among different healthcare systems. Several calculation models showed that metaphylaxis is medically and economically effective when used rationally. Rational metaphylaxis is restricted to patients with a high risk of recurrence (brushite, uric acid, cystine and infected stones, patients with residual fragments after stone treatment and recurrent calcium oxalate stone formers). CONCLUSIONS: For the groups identified, metaphylaxis is cost-effective in almost all healthcare systems, but the cost saved differs. The savings increase even more when adding the economic loss avoided from days off work due to treatment of recurrent stones. In most countries, stone frequency must exceed one stone per patient per year before medical therapy is more cost-effective than dietary measures. PMID- 26558037 TI - Low-dose unenhanced computed tomography for diagnosing stone disease in obese patients. AB - OBJECTIVE: To evaluate the detectability, size, location and density of urinary stones with unenhanced computed tomography (CT), using the half-radiation (low) dose (LDCT) technique, compared with the standard-dose CT (SDCT), in obese patients. PATIENTS AND METHODS: The study included 50 patients with a body mass index of >30 kg/m(2) and bilateral renal stones diagnosed with SDCT, and managed on one side. All the patients had LDCT during the follow-up and SDCT was used as a reference for comparison. RESULTS: Of the 50 patients, the right side was affected in 27 and the left side in 23. In all, 35 patients had a single stone while the remaining 15 had multiple stones. With SDCT, 95 stones were detected; there were 45 of ?5 mm, 46 of 6-15 mm and only four of >15 mm. LDCT barely detected three stones of <3 mm, compared with SDCT, while larger stones had the same appearance at both scans. The site of stone in the kidney or the ureter did not affect its detection on LDCT vs. SDCT. The mean stone diameter was identical in both techniques. At LDCT, all stones were detected with no difference in their number, location or density vs. SDCT. However, the tube current and radiation dose were significantly lower with LDCT. CONCLUSIONS: In obese patients with stone disease, LDCT is as accurate as SDCT, while avoiding exposure of the patient to high-dose radiation. PMID- 26558038 TI - The role of open stone surgery. AB - OBJECTIVE: To highlight the role of open stone surgery in the management of urolithiasis in the current era of minimally invasive therapies. The introduction and continuous development of extracorporeal shockwave lithotripsy (ESWL), ureterorenoscopy and percutaneous nephrolithotomy (PCNL) over the past 30 years have led to a significant change in the current management of urolithiasis, where the indications for open stone surgery have been narrowed significantly, making it a second- or third-line treatment option. METHODS: We reviewed the most recent guidelines published by the European Association of Urology and the American Urological Association, and reviewed reports through a MEDLINE search to identify the indications and current role of open stone surgery. RESULTS: From the MEDLINE search, it was obvious that the number of papers published on open renal stone surgery has decreased during the last three decades, soon after the introduction of ESWL and PCNL. CONCLUSION: Although currently most patients with stones can be managed by minimally invasive therapy, we believe that open surgery still has a role, and therefore it is of great importance to recognise that a small group of patients with complex stone disease, and those with anatomical and physiological anomalies, will benefit from this treatment option. PMID- 26558039 TI - Extracorporeal shock wave lithotripsy: What is new? AB - OBJECTIVES: Thirty years after its introduction, extracorporeal shockwave lithotripsy (ESWL) is still first-line treatment for more than half of all urinary tract stones, but machines and treatment strategies have significantly developed over time. In this review, we summarise the latest knowledge about the clinically important aspects of ESWL. METHODS: We searched PubMed to identify relevant reports and the latest European Association of Urology guidelines, and standard urological textbooks were consulted. RESULTS: New technical developments include: Twin-head and tandem-pulse shock-wave generators; wide-focus, low pressure systems; optimised coupling; and automated location and acoustic tracking systems. Indications have been refined, making possible the identification of patients in whom ESWL treatment is likely to fail. By lowering the shock-wave rate, improving coupling, applying abdominal compression, power 'ramping' and postoperative medical expulsion therapy, treatment protocols have been optimised. CONCLUSIONS: Promising new technical developments are under development, with the potential to increase the stone-free rate after ESWL. For optimal results, the refined indications need to be respected and optimised treatment protocols should be applied. PMID- 26558040 TI - Ureteroscopic treatment of larger renal calculi (>2 cm). AB - OBJECTIVES: To evaluate the current status of ureteroscopic lithotripsy (UL) for treating renal calculi of >2 cm, as advances in flexible ureteroscope design, accessory instrumentation and lithotrites have revolutionised the treatment of urinary calculi. While previously reserved for ureteric and small renal calculi, UL has gained an increasing role in the selective management of larger renal stone burdens. METHODS: We searched the available databases, including PubMed, Google Scholar, and Scopus, for relevant reports in English, and the article bibliographies to identify additional relevant articles. Keywords included ureteroscopy, lithotripsy, renal calculi, and calculi >2 cm. Retrieved articles were reviewed to consider the number of patients, mean stone size, success rates, indications and complications. RESULTS: In all, nine studies (417 patients) were eligible for inclusion. After one, two or three procedures the mean (range) success rates were 68.2 (23-84)%, 87.1 (79-91)% and 94.4 (90.1-96.7)%, respectively. Overall, the success rate was >90% with a mean of 1.2-2.3 procedures per patient. The overall complication rate was 10.3%, including six (1.4%) intraoperative and 37 (8.9%) postoperative complications, most of which were minor. The most common indications for UL were a failed previous treatment (46%), comorbidities (18.2%), and technical and anatomical factors (12.3%). CONCLUSIONS: UL is safe and effective for treating large renal calculi. While several procedures might be required for total stone clearance, UL should be considered a standard approach in the urologist's options treating renal calculi of >2 cm. PMID- 26558041 TI - Intracorporeal laser lithotripsy. AB - OBJECTIVES: To review the current literature on intracorporeal laser lithotripsy. METHODS: We searched PubMed for relevant reports up to January 2012, using the keywords 'laser', 'lithotripsy' and 'intracorporeal'. RESULTS: We studied 125 relevant reports of studies with various levels of evidence. Efficient lithotripsy depends on the laser variables (wavelength, pulse duration and pulse energy) and the physical properties of the stones (optical, mechanical and chemical). The most efficient laser for stones in all locations and of all mineral compositions is the holmium yttrium-aluminium-garnet laser (Ho:YAG). The frequency-doubled double-pulse Nd:YAG laser functions through the generation of a plasma bubble. New laser systems, such as the erbium:YAG and the thulium laser, are under evaluation. Laser protection systems have also been developed for the novel digital flexible ureteroscopes. Although complications are rare, a high relevant clinical suspicion is necessary. CONCLUSIONS: Laser lithotripsy technology is continuously developing, while the Ho:YAG laser remains the reference standard for intracorporeal lithotripsy. PMID- 26558042 TI - Positions for percutaneous nephrolithotomy: Thirty-five years of evolution. AB - OBJECTIVES: To present the chronological development of the different positions described for percutaneous nephrolithotomy (PCNL), in an attempt to identify the reasons for their development and to highlight their specific advantages and disadvantages. METHODS: Previous reports were identified by a non-systematic search of Medline and Scopus. RESULTS: The classic prone position for PCNL was first described in 1976. The technique was gradually standardised and PCNL with the patient prone became the generally accepted standard approach. In the next 35 years many other positions were described, with the patient placed prone, lateral or supine in various modifications. Modifications of the classic prone position in the early 1990s aimed to provide the option of a simultaneous retrograde approach during the procedure. As PCNL became more popular the lateral position was first described in 1994, to allow the application of PCNL to patients who were unable to tolerate being prone because of their body habitus. The supine position for percutaneous access was originally described even before 1990, but become more popular after 2007 when the Galdakao modification was reported. Several other modifications of the supine position have been described, with the latest being the flank-free modified supine position, which allows the best exposure of the flank among the supine positions. Each position has its specific advantages and disadvantages. CONCLUSION: Urologists who perform PCNL should be familiar with the differences in the positions and be able to use the method appropriate to each case. PMID- 26558043 TI - What's new in percutaneous nephrolithotomy. AB - INTRODUCTION: The goal of percutaneous nephrolithotomy (PCNL) is to ensure complete stone clearance with minimal morbidity. The key to complete clearance is accurate technique, expertise and instrumentation. METHODS: We systematically reviewed available reports that were identified using a PubMed/Medline search. The keywords used were 'PCNL' and 'advances in PCNL'. The findings were reviewed under the topics of newer developments in imaging, techniques and a review of outcomes with an emphasis on stone clearance and complications. CONCLUSION: The newer developments in imaging methods, such as cone-beam computed tomography and staghorn morphometry, help the surgeon to plan the procedure for a safe and better outcome. The highlight of these newer developments is the miniaturisation of instruments. This has translated into developing newer techniques such as the 'microperc' and 'miniperc'. The data-collection initiative by the Clinical Research Office of the Endourological Society has helped in obtaining a high level of evidence. PMID- 26558044 TI - Percutaneous nephrolithotomy for treating staghorn stones: 10 years of experience of a tertiary-care centre. AB - OBJECTIVE: To present the results of percutaneous nephrolithotomy (PCNL) for treating staghorn stones. PATIENTS AND METHODS: A database was compiled from the computerised files of patients who underwent PCNL for staghorn stones between 1999 and 2009. The study included 238 patients (128 males and 110 females) with a mean (SD) age of 48.9 (14) years, who underwent 242 PCNLs, and included staghorn stones that were present in the renal pelvis and branched into two or more major calyces. PCNL was performed or supervised by an experienced endourologist. All perioperative complications were recorded. The stone-free status was evaluated after PCNL and again after 3 months. RESULTS: Multiple tracts were needed in 35.5% of the procedures, and several sessions of PCNL were needed in 30% of patients. There were perioperative complications in 54 procedures (22%); blood transfusion was needed in 34 patients (14%). The stone-free rate for PCNL monotherapy was 56.6% (137 patients). Secondary procedures were required for 51 patients (21%), and included shock-wave lithotripsy for 49 and ureteroscopy for two. The 3-month stone-free rate was 72.7% (176 patients). Multiple tracts resulted in an insignificantly higher overall complication rate than with a single tract (P = 0.219), but the reduction in the haemoglobin level was statistically significant with multiple tracts (P = 0.001). CONCLUSIONS: PCNL for staghorn stones must be done by an experienced endourologist in a specialised centre with all the facilities for stone management and treatment of possible complications. The patients must be informed about the range of stone-free and complication rates, and the possibility of multiple sessions or secondary procedures. PMID- 26558045 TI - The management of staghorn calculi in children. AB - OBJECTIVES: To review reports focusing on the surgical treatment of staghorn stones in children, as despite all the improvements in the surgical treatment of paediatric urolithiasis the management of staghorn calculi still represents a challenging problem in urology practice. METHODS: To evaluate current knowledge about treating staghorn calculi in children, we searched PubMed for relevant articles published between 1991 and 2011, using a combination of related keywords, i.e. staghorn stone, child, kidney calculi, surgical treatment, electrohydraulic shockwave therapy (ESWL), percutaneous nephrolithotomy (PCNL), and open surgery. Reports relating to the treatment of paediatric stone disease in general (open surgery, PCNL, ESWL) were also searched with the same method. Additional references were obtained from the reference list of full-text reports. RESULTS: Although open surgery had been widely used in the past for treating such stones in children, currently it has only limited indications in highly selected patients. Current published data clearly indicate that, in experienced hands, both PCNL and ESWL are now effective methods for treating staghorn calculi in children. CONCLUSIONS: Due to advanced techniques and instrumentation, it is now possible to successfully treat staghorn calculi in children, with very limited safety concerns. Currently, while PCNL is recommended as the first-line surgical treatment, ESWL, open surgery and/or combined methods are valuable but secondary options in the treatment of paediatric staghorn calculi. PMID- 26558047 TI - Improving the compliance of the recurrent stone-former. AB - OBJECTIVE: To provide an overview of aspects of compliance by the recurrent stone former, and to give recommendations for its improvement. About half of all stone formers have one recurrence during their lifetime. To avoid recurrent stone formation it is necessary to use metaphylaxis, based on individual risks. However, all general and specific efforts are meaningless if patients are not willing or are incapable of following the proposed therapy in the long-term. METHODS: PubMed was searched for articles on urolithiasis, metaphylaxis, compliance and adherence, and relevant papers were reviewed. RESULTS: Compliance is a multidimensional phenomenon which is determined by the interaction of different factors, i.e. social and economic, therapy-related, patient-related, condition-related, and healthcare team and system-related factors. Subsequently there are several different interventional possibilities at the urologist's disposal to effect better compliance by the patient. CONCLUSIONS: The treatment and metaphylaxis of the recurrent stone-former present a particularly pertinent challenge. Patient compliance has an immense influence on the success of the treatment with respect to metaphylaxis, which is the decisive factor for preventing stone recurrence. PMID- 26558046 TI - Extracorporeal shockwave lithotripsy vs. percutaneous nephrolithotomy vs. flexible ureterorenoscopy for lower-pole stones. AB - OBJECTIVES: To review previous reports and discuss current trends in extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and ureterorenoscopy (URS). ESWL was recommended as the first-line treatment for small and intermediate-sized stones in the lower pole, while it is the standard treatment for large stones. However, the stone clearance rate after ESWL seems to be lower than that of stones in other locations. This seems to result from a lower rate of fragment passage, due to anatomical factors. METHODS: Reports on urinary stone disease were reviewed, assessing only publications in peer reviewed, Medline-listed journals in the English language (publication years 1990 2011). RESULTS: Recent experience with flexible URS (fURS) for intrarenal stones showed that excellent stone-free rates can be achieved. With increasing experience and technically improved equipment, fURS has become an alternative to ESWL for small and intermediate-sized renal stones. Furthermore, several authors reported successful retrograde treatment for large renal stones, proposing fURS as an alternative to PCNL. However, the major drawbacks are long operating times and commonly, staged procedures, which is why PCNL remains the method of choice for such stones. CONCLUSIONS: Considering the currents trends and evidence, the 2012 update of the European Association of Urology Guidelines on Urolithiasis has upgraded the endourological treatment of kidney stones. Individual factors such as body habitus, renal anatomy, costs and patient preference must be considered. PMID- 26558048 TI - Extraperitoneal laparoscopic radical prostatectomy: A prospective 2-year single surgeon experience with 171 cases. AB - OBJECTIVE: To assess the safety and the oncological and functional efficacy of a prospective series of extraperitoneal laparoscopic radical prostatectomy (ELRP). PATIENTS AND METHODS: This prospective study included 171 consecutive patients (mean age 62.9 years, SD 6.5) who underwent ELRP by one surgeon between January 2008 and December 2009. The variables analysed were operative duration, blood loss, conversion rate, complications, hospital stay, duration of catheterisation, and the oncological results. We also assessed the rates of continence and erectile function. RESULTS: There were no conversions to open surgery. The mean (SD) operative duration was 112.7 (19.4) min, the blood loss was 372.1 (219.1) mL, the hospital stay was 6.8 (2.0) days, and the duration of catheterisation 6.7 (1.5) days. Collectively, 23.4% (40/171) of patients had positive surgical margins. Urinary continence at 1, 3, 6 and 12 months was achieved in 63.3% (95/150), 88.6% (78/88), in 90.3% (121/134) and 92.1% (117/127) of patients, respectively. The respective percentages for physiological erections after nerve sparing ELRP at the same times were 11.8% (13/110), 11.8% (13/110), 18.2% (20/110) and 25.5% (28/110). The overall potency recovery rates (including patients on pharmacotherapy) were, respectively, 26.4% (29/110), 35.5% (39/110), 52.7% (58/110) and 69.1% (76/110), for the nerve-sparing procedure. CONCLUSION: ELRP gave good oncological and functional results, especially in terms of urinary continence. PMID- 26558049 TI - Retrograde upper-pole calyceal access for percutaneous nephrolithotripsy of stones in the lower-pole calyx. AB - OBJECTIVE: To present the results of upper calyceal access during percutaneous nephrolithotripsy (PCNL) for stones in the lower calyx, as PCNL is considered the most effective minimally invasive surgery for managing lower calyceal stones, with percutaneous access either directly to the lower calyx or through an upper or middle calyx. PATIENTS AND METHODS: The study included 76 patients with single (51) and multiple (25) stones in the lower calyx, and stones in the lower calyx plus renal pelvis (six) and associated pelvi-ureteric junction obstruction (PUJO, five). They were managed by PCNL using retrograde access through the upper-pole calyx in addition to laser endopyelotomy for the PUJO. RESULTS: The mean duration required for establishing the retrograde nephrostomy tract was 14.4 min, and for completing the procedure was 40 min. The mean fluoroscopy exposure time was 3.2 min. Access from the upper calyx allowed easy and rapid advancement of the nephroscope to the lower calyx. The stones varied in size, at 10-25 mm. Stones were cleared completely in 70 of the 76 patients (92%); the stone-free rate was 100%. The residual stone fragments (2-4 mm) in the remaining six patients (8%) were considered insignificant. Complications were minor in four patients (5%), and included pleural effusion in two, bleeding in one and an arteriovenous fistula in one. CONCLUSIONS: Upper-pole calyceal access for PCNL provides easy and effective clearance of stones in the lower calyx. This access should be considered for PCNL of single or multiple stones in the lower calyx. PMID- 26558050 TI - A supracostal approach for percutaneous nephrolithotomy of staghorn calculi: A prospective study and review of previous reports. AB - OBJECTIVES: To evaluate a supracostal approach for percutaneous nephrolithotomy (PCNL) of staghorn calculi through a prospective study and review of previously reported cases. METHODS: From June 2009 to November 2011, 40 patients with staghorn calculi were scheduled for supracostal S-PCNL in a prospective study. Of the 40 renal units, 16 (40%) had a complete staghorn and 24 (60%) had a partial staghorn calculus. Perioperative complications were stratified according to the modified Clavien system. Univariate and multiple logistic regression analyses were used to determine statistically significant variables affecting the stone free rate and development of complications. RESULTS: In all, 57 tracts were established in the 40 renal units; 23 (58%) renal units were approached through one supracostal upper pole calyx, while 13 (33%) and four (10%) required a second middle- or lower-pole puncture, respectively. Overall, 78% of patients were rendered stone-free or had clinically insignificant residual fragments with PCNL monotherapy, and this increased to 88% with auxiliary procedures. In the logistic regression analysis, a complete staghorn stone was the only independent variable for residual stones (P = 0.005). There was an overall complication rate of 38%. Independent variables with an influence on complications were staghorn stone burden (P = 0.007), and operative duration (P = 0.045). CONCLUSIONS: The supracostal upper calyceal approach provides optimum access for the percutaneous removal of staghorn stones. Appropriate attention to the technique and to monitoring before and after surgery can detect thoracic complications, and these can be managed easily with intercostal chest tube drainage, with no serious morbidity. PMID- 26558051 TI - Is an overnight stay after percutaneous nephrolithotomy safe? AB - OBJECTIVES: To establish a clinical care pathway that plans for hospital discharge the day after percutaneous nephrolithotomy (PCNL), to evaluate the safety, effectiveness and feasibility of this pathway, and to identify factors associated with a postoperative length of hospital stay (LOS) of >1 day. PCNL is the treatment of choice for patients with large kidney stones and those in whom extracorporeal shockwave lithotripsy has failed, and the mean LOS is typically 2 5 days. PATIENTS AND METHODS: We retrospectively reviewed the charts of 109 patients (mean age 57.4 years; 58 men, 53%) who had PCNL between 2006 and 2009. All had nephrostomy tubes placed after surgery. The patients' demographics, LOS, incidence of complications, clinical outcomes, stone-free rates, number of early postoperative emergency-room visits, need for subsequent admission and/or other procedures, were noted and analysed. The modified Clavien classification was used to describe the postoperative complications. Bivariate analyses were used to test for associations between LOS and other variables. RESULTS: The mean (range) stone size was 2.2 (0.9-5.9) cm, and the mean (SEM) LOS was 1.7 (0.13) days. Of the 109 patients, 20% had a LOS of >1 day for surgical, 3% for medical and 5% for social reasons. The stone-free rate was 89%. There was no difference in the number of subsequent hospital visits or ancillary procedures for patients discharged after one or more postoperative nights. No variables were associated with a longer LOS. CONCLUSIONS: An overnight hospital stay after PCNL is safe and represents an effective strategy for improved bed use in selected patients. A longer LOS was not affected by patient age or body mass index, stone size or operative time. We continue to use our clinical care pathway, as supported by these data. PMID- 26558052 TI - Complications and outcomes of JJ stenting of the ureter in urological practice: A single-centre experience. AB - OBJECTIVE: To determine the factors affecting the development of complications and the outcomes of JJ stenting. PATIENTS AND METHODS: The study included 220 patients (133 males and 87 females, mean age 39.5 years, SD 15.4) who had self retaining JJ ureteric stents placed while in the authors' institution. Univariate and multivariate analyses were used to identify the significant variables affecting the development of complications and outcome of stenting (condition 'improved' or 'not improved'). RESULTS: Using a modified Clavien classification, there were grade I, II, IIIa, IIIb complications in 67 (30.4%), 39 (17.7%), two (0.9%) and 23 (10.5%) patients, respectively, and none of grades IVa, IVb and V. Loin pain (10.9%) and urinary tract infection (10.9%) were the most common complications, followed by dysuria (7.7%). There were significant complications requiring treatment in 29% of patients, and 71.4% of patients improved after stenting. On multivariate analysis the significant independent factor affecting the complication rate was the stent length (P = 0.016), and the significant independent factor affecting the 'improved' outcome was age (P = 0.014). CONCLUSION: Longer stents are associated with increased complication rates, and the older the patient the more likely they are to have a poor outcome after stenting. Future prospective multicentre studies with more patients are needed to confirm the present conclusions. PMID- 26558053 TI - 'Minipatch' penile skin graft urethroplasty in the era of buccal mucosal grafting. AB - OBJECTIVES: To describe our experience with 'minipatch' penile skin graft (PSG) urethroplasty, as at our institution we prefer excision and primary anastomosis (EPA) urethroplasty whenever feasible, as it gives better outcomes than substitution urethroplasty. However, despite careful preoperative planning, the unanticipated need for a small graft is occasionally recognised intra operatively, and in such cases we have found that harvesting a minipatch is an efficient alternative to harvesting a buccal mucosal graft. PATIENTS AND METHODS: Bulbar urethroplasty using a <3 cm PSG was performed via either a ventral onlay or augmented anastomotic technique. In each case the PSG was required to repair an unanticipated urethral defect recognised intra-operatively during various scenarios of challenging urethroplasty. We retrospectively reviewed our experience with this technique. RESULTS: Among a total of 425 urethral reconstructions over a 4-year period at our institution, four patients (1%) underwent minipatch PSG urethroplasty to repair either urethral strictures that were discovered intra-operatively to be too complex for EPA (two patients) or for intra-operatively identified, unanticipated synchronous strictures (two patients). The mean (range) stricture length was 2.4 (2-3) cm and the mean graft length was 2.1 (1.5-2.5) cm. At a mean follow-up of 18 months all repairs were patent with no need for further procedures or instrumentation. CONCLUSION: Minipatch PSG urethroplasty is an efficient alternative to a buccal mucosal graft repair, especially when the unanticipated need for short-segment tissue transfer arises during complex urethral reconstruction. PMID- 26558054 TI - Phalloplasty for an amputated phallus in intersex patients. AB - OBJECTIVE: To report our experience of phalloplasty using a radial forearm free flap (RFF) and insertion of a penile prosthesis for the amputated phallus. PATIENTS AND METHODS: Phalloplasty was carried out in nine intersex patients with ambiguous genitalia as a result of female circumcision, with a consequent partial or complete excision of their microphallus. Six months later a penile prosthesis was inserted in the periostium of the lower border of the symphysis pubis in the first six patients. RESULTS: All patients were fully satisfied with the size and cosmetic appearance of their penis. One patient had a urinary fistula that was closed surgically. All of the patients are continent. The penile prosthesis was implanted successfully with no complications. CONCLUSIONS: Phalloplasty using a RFF and insertion of a penile prosthesis for the amputated phallus are technically feasible, with good clinical and functional outcomes. PMID- 26558055 TI - Does intravenous cefuroxime improve the efficacy of ciprofloxacin for preventing infectious complications after transrectal prostate biopsy? A prospective comparative study. AB - OBJECTIVES: To compare the frequency of infection after transrectal ultrasonography (TRUS)-guided biopsy of the prostate (TRUSBP) using prophylactic ciprofloxacin with or without adding cefuroxime. PATIENTS AND METHODS: Between June 2008 and October 2009, 205 consecutive patients had TRUSBP with the use of oral 500 mg ciprofloxacin twice per day, 2 days before and 3 days after the biopsy (defined as group A). Starting from November 2009 and onwards, 250 consecutive patients had TRUSBP using the same previous protocol of antibiotic prophylaxis but with the addition of intravenous 1.5 g cefuroxime given 30 min before the procedure (defined as group B). The incidence of sepsis after TRUSBP, together with the results of urine and blood cultures and antibiotic sensitivity, were compared between the groups. RESULTS: Fever after TRUSBP was recorded in 18 of 205 patients in group A (8.8%) and in nine of 250 in group B (3.6%); the difference was significant (P = 0.018). Urine culture was positive in 14 and five of patients in groups A and B, respectively, with extended-spectrum beta lactamase-producing (ESBL) Escherichia coli as the most common organism. The blood culture was positive in seven and three patients in groups A and B, respectively, with ESBL E. coli as the most common organism. All patients who had sepsis after TRUSBP sepsis were treated successfully. CONCLUSION: Adding a single intravenous injection with 1.5 g of cefuroxime to oral ciprofloxacin significantly reduced the frequency of infectious complications after TRUSBP. PMID- 26558057 TI - Editorial comment to "The value of percentage free prostate-specific antigen (PSA) in the detection of prostate cancer among patients with intermediate levels of total PSA (4.0-10.0 ng/mL) in Nigeria" and Reply by authors. PMID- 26558056 TI - The value of percentage free prostate specific antigen (PSA) in the detection of prostate cancer among patients with intermediate levels of total PSA (4.0-10.0 ng/mL) in Nigeria. AB - OBJECTIVES: To assess the value of percentage free prostate-specific antigen (%fPSA) in the detection of prostate cancer among Nigerian men with an intermediate total PSA level (4-10 ng/mL), and to show if the optimum threshold for biopsy is different from Caucasian values when the widely used (six-core, digitally directed) prostate biopsy protocol in Nigerians is applied. PATIENTS AND METHODS: The study included 105 patients aged >50 years, with a palpably benign prostate gland and intermediate levels of total PSA (4-10 ng/mL). These patients had a free PSA assay and a transrectal digitally directed six-core biopsy of the prostate. The %fPSA was calculated and the optimum threshold value for detecting prostate cancer was determined. RESULTS: The mean (SD) age of the patients was 64.4 (6.6) years and their mean (SD) total PSA level was 6.6 (1.7) ng/mL. Of these men 14 (13.3%) had cancer of the prostate detected by the prostate biopsy. The %fPSA level related directly to sensitivity values but inversely to the specificity and the positive predictive values. The best threshold of %fPSA for detecting cancer in these men was <40%, with a sensitivity of 100%, specificity of 93.4% and a positive predictive value of 70% (P < 0.05). CONCLUSIONS: In evaluating Nigerian patients with a palpably benign prostate gland and within the intermediate total PSA range, when digitally directed biopsy protocol is adopted, a %fPSA threshold of <40% will detect significant percentage of those with prostate cancer, with a minimal number of unnecessary biopsies. This value differs from that reported in western studies in which transrectal ultrasonography-directed biopsy was used. PMID- 26558058 TI - Factors that predict the spontaneous passage of ureteric stones in children. AB - OBJECTIVE: To study the natural history of stone passage in children with ureterolithiasis and to define factors predictive of spontaneous passage. PATIENTS AND METHODS: In all, 72 children with ureteric stones were evaluated; patients with ureteric calculi of >10 mm were excluded, as were those with absolute indications for surgical stone removal. Stone size, location, side, presence of hydronephrosis, perinephric stranding and degree of the tissue-rim sign were estimated by unenhanced helical computed tomography (UHCT). All patients were sent home with no administration of an alpha-blocker. The stone status was evaluated by a plain abdominal film or CT at ~6 weeks after the initial diagnostic evaluation. The time from the initial complaint to the passage of the stone was recorded for each patient. RESULTS: In all, 54 (75%) children with ureteric stones of ?6 mm eventually passed their stones spontaneously. However, stones of <4 mm and those in the distal ureter had a significantly higher spontaneous passage rate and shorter time to stone passage (P < 0.05). The UHCT findings of a higher degree of the tissue-rim sign, hydronephrosis and perinephric fat stranding were associated with a lower likelihood of stone passage. CONCLUSIONS: The rate of spontaneous passage of ureteric stones in children varies with stone location, and perinephric stranding on UHCT seems to be useful for predicting the possibility of spontaneous passage. In cases with unfavourable signs an early intervention might have better outcomes than conservative therapy. PMID- 26558059 TI - Single vs. double dartos layers for preventing fistula in a tubularised incised plate repair of distal hypospadias. AB - OBJECTIVE: To compare the outcome of a single vs. a double-layer dartos interposition for preventing a fistula after tubularised incised-plate (TIP) distal hypospadias repair. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with primary distal hypospadias who had the hypospadias repaired between February 2009 and June 2011, operated by one surgeon (S.A.K.). In all of the children a standard TIP urethroplasty was performed, which was covered by a dartos fascial flap fashioned using one of two techniques, i.e. in Group I (48 patients) double dartos preputial flaps were used, and in Group II (52 patients) a single dorsal dartos flap was used and transposed ventrally via a 'buttonhole'. The fistula rate and other complications related to each group were recorded. RESULTS: The mean (range) follow-up was 12 (6-22) months for Group I and 14 (6-24) months for Group II. The result was considered a success in 96% of Group I and 92% of Group II. In Group I there were no fistulae, while in Group II there were four fistulae (8%) detected; this difference was statistically insignificant (P = 0.1). Meatal stenosis was associated with a fistula in one patient in Group II but not in the other three. In Group I a meatal stenosis developed late after complete healing of the urethroplasty, with no associated fistula. The repair broke down in one patient in Group I (2%). CONCLUSION: A double-dartos neourethral cover in TIP hypospadias repair seems to be more effective than a single layer for preventing a fistula, despite there being no statistically significant difference between the groups. However, the protective effect of double-dartos flaps must be appropriately evaluated in a prospective, randomised and controlled study in more patients. PMID- 26558060 TI - Minimally invasive treatment of ureterovaginal fistula: A review and report of a new technique. AB - BACKGROUND: An iatrogenic ureterovaginal fistula (UVF) can be a consequence of difficult pelvic surgery. The patient must endure a long wait before having major surgery to reconstruct the injured ureter. Reports that address the minimally invasive treatment of UVF are limited, and are reviewed here. We introduce the concept of using a MemokathTM 051 stent (PNN A/S, Hornbaek, Denmark) as a promising minimally invasive approach for UVF. METHODS: We used PubMed, Science Direct, Google and the Cochrane Library to assemble appropriate evidence-based reference reports. The keywords used for the search were: 'Memokath', 'stent'; 'ureterovaginal fistula' and 'ureteral injury'. The review showed 42 relevant articles published up to September 2011. RESULTS: Ureteric stenting consistently stopped the vaginal leak of urine. The long-term results were not encouraging after removing the JJ stents at 3 months after insertion. Most patients had a recurrence of the vaginal leak of urine. The outcome was different with the Memokath stent, that remained in situ for a duration far exceeding that of the JJ stent. The Memokath stopped the vaginal leak of urine with no episodes of urinary tract infection and no evidence of stent migration. CONCLUSION: Long-term ureteric stenting has two advantages, in that it facilitates urine flow through the ureteric strictured segment down to the bladder, and it stops urine leakage along the fistula. It further promotes the resolution of the ureteric stricture and healing of the fistula. A duration of 3 months was inadequate when a JJ stent was used, whereas longer periods are possible with the Memokath stent. The optimum stenting period required for complete healing of a UVF remains to be defined. Long-term Memokath ureteric stenting can be an effective alternative and minimally invasive approach to conventional surgical repair in selected cases. PMID- 26558061 TI - Protection against renal ischaemia/reperfusion injury: A comparative experimental study of the effect of ischaemic preconditioning vs. postconditioning. AB - OBJECTIVE: To compare the effect of ischaemic preconditioning (Ipre) vs. ischaemic postconditioning (Ipost) on renal ischaemia/reperfusion (I/R) injury in rats. MATERIALS AND METHODS: In all, 120 male Sprague-Dawley rats were classified into four groups of 30 rats each, designated sham, control, Ipre and Ipost. Renal function, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), fractional Na excretion (FENa) and renal histopathology were measured at 2, 24 and 48 h after ischaemia. Markers of lipid peroxidation (malondialdehyde, MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in kidney tissues during the same intervals. RESULTS: Ipre caused a significant improvement in renal function, as indicated by a significant decrease in serum creatinine, BUN and FENa, with a significant increase in CrCl. However, Ipost caused no significant improvement in renal function. Morphologically Ipre caused a marked significant improvement in the renal tubular damage score compared to Ipost. Also, Ipre caused a significant decrease in MDA, and significant increase in GSH and SOD when compared to Ipost. CONCLUSION: Ipre is more potent than Ipost for improving the renal injury induced by I/R. Ipre caused a marked improvement in renal function and morphology, while Ipost caused a minimal improvement in morphology only. Moreover, Ipre caused a marked and significant reduction in oxidative stress in kidney tissues, while Ipost caused a minimal reduction. PMID- 26558062 TI - Does pentoxifylline enhance the recovery of erectile function after a T-shunt procedure for prolonged ischaemic priapism? A prospective randomised controlled trial. AB - OBJECTIVE: To evaluate the role of oral pentoxifylline for enhancing the recovery of erectile function (EF) in patients who had a T-shunt, a technically simple procedure for treating prolonged ischaemic priapism, as the recovery of EF has been reported in many patients treated by this procedure. PATIENTS AND METHODS: This prospective randomised study was conducted on 40 patients with prolonged ischaemic priapism treated with a T-shunt. Patients were randomly divided into two groups; group A received oral pentoxifylline from the second day after surgery for 3 months, and group B received placebo. Patients were followed for 18 months. RESULTS: The pain resolved in all patients, and EF recovered in 15 patients in group A and 10 in group B within 3 months. All patients but three had recovery of EF within the 18-month follow-up. Six patients had recovery of EF by using on-demand 50 mg sildenafil. The three patients who did not recover EF had a penile prosthesis implanted after the end of the study. CONCLUSION: Pentoxifylline had no significant effect on the recovery of EF after a T-shunt procedure, but a larger study (double-blinded) is required for a more accurate assessment of any beneficial effect of pentoxifylline after a T-shunt procedure. PMID- 26558063 TI - Congenital penile curvature presenting as unconsummated marriage. Repair by 16 dot plication with subjectively reported patient and partner satisfaction. AB - OBJECTIVE: To evaluate self-reported patient and partner satisfaction in cases of unconsummated marriage due to congenital penile curvature that was treated by the 16-dot plication procedure. PATIENTS AND METHODS: From March 2008 to March 2012, 24 couples presented to our institute with an unconsummated marriage due to congenital penile curvature. All patients were treated using the 16-dot plication operation. Patients were followed up for 3 months and were asked, with their partners, to complete a specific questionnaire to evaluate their satisfaction with the outcome of the operation. RESULTS: The duration of unconsummated marriage was 2-12 weeks. The mean (SD, range) angle of penile curvature was 57.4 (20.3, 30-110) degrees . All patients were able to consummate their marriage within a mean (SD, range) of 5.3 (1.3, 4-8) weeks after surgery. The overall satisfaction rate with the outcome of the operation among patients was nearly 100% for 'moderately satisfied' or greater, and among their partners was nearly 96% for 'moderately satisfied' or greater, at 3 months. CONCLUSION: The 16-dot plication technique is an easy procedure for the emergent correction of congenital penile curvature presenting as an unconsummated marriage. Most patients and their partners were pleased with the outcome of the procedure. PMID- 26558064 TI - The effect of magnified bilateral varicocele ligation on semen quality and the natural paternity rate in subfertile men, based on the sum of varicocele grading. AB - OBJECTIVE: To evaluate the effect of magnified bilateral varicocele ligation on the semen quality and natural paternity rate in subfertile men, based on the sum of varicocele grading. PATIENTS AND METHODS: In a prospective longitudinal study, 78 patients (mean age 36.5 years, range 21-56) with a total of 156 varicoceles underwent bilateral varicocele ligation. Patients included had bilateral, primary and clinically palpable varicoceles, with a normal hormonal profile and abnormal semen; patients excluded had unilateral varicocele, or were recurrent cases, had infraclinical varicocele or had a genetic abnormality. Patients were classified into five groups (A-E), based on the findings of a physical examination; A included 13 patients with grade sum II (I + I), B included 21 with grade sum III (II + I), C included 25 with grade sum IV (II + II) or (III + I), D included 11 with grade sum V (III + II) and E included eight with grade sum VI (III + III). The follow-up was scheduled at 3, 6 and 12 months to assess semen variables and the natural paternity rate; 16 patients continued to a 36-month follow-up. Data were analysed statistically using a paired t-test to compare the mean sperm variables before and after surgery, with P < 0.05 considered to indicate significant differences. RESULTS: Of the 78 patients, 74 completed the follow-up at 3 months and only seven missed the 6-month follow-up. Overall, the mean sperm density, total sperm motility and sperm morphology increased from 13.44 to 26.48 * 10(6)/mL, 27.4% to 53% and 41.4% to 65.0%, respectively; the differences were statistically significant for all variables (P < 0.001). For each group separately there were significant improvements for both sperm density and motility, but for sperm morphology there were significant improvements in all groups except E, where the improvement was not correlated with those in the other groups. The paternity rate (by natural pregnancy) at 2 years was 26.9%, and this increased to 41% within 3 years. CONCLUSION: Magnified bilateral varicocele ligation based on the sum of varicocele grading significantly improved semen quality and the natural paternity rate in subfertile men. PMID- 26558065 TI - Increase in fracture of the penis in south-west Nigeria. AB - OBJECTIVE: To present our recent experience in the management of penile fracture. PATIENTS AND METHODS: We present 21 cases of penile fracture managed at the two Federal-owned tertiary hospitals in two neighbouring states in south-west Nigeria between 2001 and 2011. The diagnosis was based mainly on a clinical evaluation. The treatment was surgical in patients who presented within 2 weeks of the fracture. The emphasis during the follow-up was on erectile function and micturition. RESULTS: Seventeen patients presented within 48 h, two presented after a week, while two reported months later with penile deviation. The mean age of the patients was 26.4 years. The cause of fracture was sexual intercourse in 11 (52%) patients and forceful manipulation of the erect penis in 10 (48%). Thirteen (62%) of all injuries occurred in the last 2 years of the study, of which eight men were injured during rear entry with the woman on top (reverse coital) position. Six of the patients with reverse coital injuries reported trying the position after watching it on the Internet, specifically on their cellular phones. Eighteen patients had surgical treatment, with a satisfactory outcome. Two of the other three patients had penile deviation during erection. CONCLUSIONS: The incidence and causes of penile fracture appear to have changed drastically over the last 2 years in our environment. The rapid demographic changes in south-west Nigeria are probably responsible. There appears to be a relationship between the cause of fracture and the use of the Internet, although that might be coincidental. Surgical repair, irrespective of the delay before intervention, usually offers a satisfactory outcome. PMID- 26558066 TI - A visit to Mansoura Urology & Nephrology Center, Mansoura, Egypt. PMID- 26558067 TI - Establishing the subspecialty of female pelvic medicine and reconstructive surgery in the United States of America. AB - OBJECTIVE: In this review I describe the history leading to the creation of the subspecialty of female pelvic medicine and reconstructive surgery and its fellowships, the process involved in the current requirements for subspecialty certification and fellowship applications, and the implications for urological training. RESULTS AND CONCLUSIONS: The route to subspecialty certification and fellowships for female urology in the USA is a lesson in politics, education, medical rivalries and perseverance, with the goal of improving care for women. This decade-long journey culminated in the recognition of a separate subspecialty by the American Board of Medical Specialties in 2011, accreditation by the American Council for Graduate Medical Education in 2012, and certification to be awarded by the Boards of Obstetrics and Gynecology and Urology in 2013. It remains to be seen whether this effort will improve resident education and patient care, or represent a marketing tool in the competitive USA healthcare environment. While many of the details and regulatory issues are specific to the USA, elements of the curriculum and procedures should be relevant to other countries. PMID- 26558068 TI - The fate of synthetic mid-urethral slings in 2013: A turning point. AB - INTRODUCTION: Since the introduction of the first retropubic tension-free synthetic sling to treat stress urinary incontinence (SUI), newer approaches, different techniques and new devices have been created. Transobturator and single incision sling (SIS) techniquespara-were developed with the goal of diminishing the rate of complications andspeeding the recovery phase. METHODS: For this review we searched Medline for relevant papers, with an emphasis on meta-analysis and randomised controlled trials (RCTs). Specially selected reports were identified to address both 'index patients' (defined as those with genuine SUI and no previous anti-incontinence procedure or other genitourinary sign or symptom that might affect her SUI) and, briefly, non-index patients. Two authors independently reviewed papers for eligibility. RESULTS: Level 1 evidence from a Cochrane review and two meta-analyses indicated that subjective outcomes with the mid-urethral sling (MUS) were similar to those from colposuspension. However, the MUS was better than colposuspension when assessing objective outcomes (Level 1). MUS are equally effective as autologous pubovaginal slings (Level1). Two meta analyses suggest that retropubic MUS (RMUS) might be better than transobturator MUS when assessing objective outcomes. Five more recent RCTs with longer term outcomes showed high success rates and only one reported a significant advantage for the RMUS in women with intrinsic sphincteric deficiency. One meta-analysis addressing the SIS showed inferior outcomes to the MUS (Level 1). New and improved SIS techniques have been used, but long-term outcomes are limited and results are still controversial when compared to the MUS. CONCLUSION: MUS are still the standard to treat the index patient as previously stated by the American and European Associations of Urology. Currently data are lacking to define which sling and what approach works best. Complications are significantly different between sling types and are dependent on technique. PMID- 26558069 TI - Different urodynamic patterns in female bladder outlet obstruction: Can urodynamics alone reach the diagnosis? AB - OBJECTIVE: To define the different urodynamic patterns in female bladder outlet obstruction (BOO) and to assess whether urodynamics alone can be relied on for the diagnosis. PATIENTS AND METHODS: This prospective study included 60 clinically obstructed women and 27 with stress urinary incontinence as a control group. All patients had pressure-flow studies and were divided into four groups. Group A (control group, 27 patients) and group B (22) had a maximum urinary flow rate (Q max) of >15 mL/s and a detrusor pressure at Q max (P det Q max) of <30 or >30 cm H2O, respectively. Group C (20 patients) and group D (18) had a Q max of <15 mL/s and a P det Q max of >30 or <30 cm H2O, respectively. RESULTS: The mean Q max for groups A, B, C, and D were 21.8, 21.9, 10.8 and 9.9 mL/s, respectively, while the mean P det Q max was 20.8, 40.4, 48.7, and 18.7 cm H2O, respectively. The residual urine volume was <100 mL in groups A and B but >100 mL in groups C and D. When compared with group A, groups B-D had a significant difference in vesical pressure, groups B and C had a significant difference in P det Q max, while Q max, the maximum voided volume and residual urine volume were significantly different in groups C and D. Group A was obviously unobstructed, group B might have early obstruction, group C had compensated obstruction, while group D can be considered to have late de-compensated obstruction. CONCLUSIONS: BOO in females has three different urodynamic patterns, i.e. early, compensated and late obstruction. However, urodynamics should be combined with the clinical presentation and residual urine volume for an accurate diagnosis. PMID- 26558070 TI - Posterior tibial nerve stimulation as treatment for the overactive bladder. AB - OBJECTIVE: To evaluate the efficacy of posterior tibial nerve stimulation (PTNS) as a treatment for the overactive bladder (OAB) resistant to medical treatment. PATIENTS AND METHODS: The study included 60 patients, comprising 55 women (92%) and five men (8%) with a mean (SD) age of 41.4 (10.8) years, who presented to the Urology Department of Benha University Hospital from June 2010 to October 2012. All patients were assessed initially by taking a history, a physical examination, urine analysis, routine laboratory investigations, and a urodynamic evaluation in the form of flowmetry, cystometry, and a pressure-flow study in some cases. A voiding diary (daytime and night-time frequency, voiding volume, and leakage episodes) was completed by all patients, and all underwent 12 sessions of PTNS using a personal computer-based system, and were reassessed after the sixth session, at the end of the course, and at 3 and 6 months after the last session, using the same methods as in the baseline visit. RESULTS: There was a statistically significant improvement in all the variables assessed. No infection or failure of the PTNS mechanism was detected while using the technique, but there were rare instances of minor bleeding and a temporary painful feeling at the insertion site. CONCLUSION: PTNS is safe, and gives statistically significant improvements in the patient's assessment of OAB symptoms. PMID- 26558071 TI - Semi-rigid ureteroscopy for ureteric and renal pelvic calculi: Predictive factors for complications and success. AB - OBJECTIVE: To analyse and compare the effect of stone site and size, method of lithotripsy, and level of experience on the results and complications of semi rigid ureteroscopy for ureteric and renal pelvic stones. PATIENTS AND METHODS: Between April 2010 and May 2011, 90 patients underwent 95 ureteroscopies, using 7.5- and 9-F semi-rigid ureteroscopes, with or without pneumatic or laser lithotripsy. The peri-operative findings were analysed and compared. RESULTS: The mean (SD) longest diameter of the stones was 11.8 (4.5) mm. Laser lithotripsy was used in 32 cases and pneumatic lithotripsy in 26. There were complications in 35 procedures in the form of colicky pain (2%), haematuria (1%), stone migration (7%), equipment failure (5%), access failure (8%), mucosal injury (7%), fever (2%) and extravasation (3%).The calculi were successfully retrieved in 75 patients (83%). The success rate was 95%, 77%, 85%, and 53% in the lower, middle, upper ureter and renal pelvis, respectively. CONCLUSIONS: Upper ureteric stones can be managed safely with the semi-rigid ureteroscope. Renal pelvic stones are associated with a lower success rate, and thus they were not a primary indication for ureteroscopic intervention. The secondary ureteroscopic management of renal pelvic stones improved the results of subsequent alkalinisation or shock-wave lithotripsy if they could not be eradicated completely. The failure rate was significantly small in lower ureteric stones and stones of <10 mm. Less experience, a stone size of >15 mm and patients ?2 years old were associated with more complications or a lower success rate. There was no significant difference in the success or complication rate between laser and pneumatic lithotripsy. PMID- 26558072 TI - Efficacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones. AB - OBJECTIVE: To evaluate and compare the efficacy of tamsulosin and alfuzosin as medical expulsive therapy for ureteric stones. PATIENTS AND METHODS: In all, 112 patients with ureteric stones of ?10 mm, located along the ureter, were randomly divided into three groups. In group I, 32 patients received no alpha-blockers (controls), in group II 40 patients received tamsulosin 0.4 mg daily, and in group III 40 patients received alfuzosin 10 mg daily. All patients were given analgesia and antibiotics when indicated. The follow-up was weekly for 4 weeks. RESULTS: The mean stone size and age were comparable in the three groups. The stone expulsion rate was 44%, 85% and 75% in groups I, II and III, respectively. Half of the stones in group II passed within 2 weeks, half in group III passed within 3 weeks, while more than half of the stones in group I did not pass even after 4 weeks. The mean number of painful episodes was 2.45, 1.38 and 1.64 in groups I, II and III, respectively. The drug-related side-effects reported by patients were mild and transient. CONCLUSION: The use of tamsulosin or alfuzosin as medical expulsive therapy for ureteric stones in the three sections of the ureter (upper, middle and lower) was safe and effective, as shown by the increased overall stone expulsion rate, reduced stone expulsion time and fewer pain episodes. Tamsulosin was associated with a greater rate of stone expulsion than was alfuzosin. PMID- 26558073 TI - Double-J ureteric stenting in pregnancy: A single-centre experience from Iraq. AB - OBJECTIVES: To evaluate the safety and effectiveness of ureteric stenting with a JJ stent in pregnant women, to relieve renal obstruction and intractable flank pain. PATIENTS AND METHODS: All pregnant patients presenting with intractable flank pain, with or without complications, to a tertiary national teaching hospital in Kurdistan/Iraq, and necessitating ureteric stenting with a JJ stent, were prospectively assessed for this study between March 2008 and March 2010. RESULTS: In all, 30 pregnant patients presented with intractable flank pain necessitating JJ ureteric stenting during the 25 months. Intractable flank pain (23 patients, 77%) was the most common indication for ureteric stenting, followed by flank pain with clinical sepsis (six, 20%). All pregnant women had hydronephrosis on ultrasonography (US), and 12 (40%) had evidence of coexisting renal stones on US. All ureteric stents were inserted successfully. The mean (range) indwelling time was 47.4 (3-224) days. Radiologically, 14 (47%) and 15 (50%) had complete resolution of the hydronephrosis on follow-up US in late pregnancy and in the early postnatal period, respectively. Two-thirds of patients had a clinical improvement immediately (15, 50%) and soon after (five, 17%) surgery. Stent encrustation (three, 10%), stent migration (three, 10%) and stent irritation (five, 17%) were reported as complications. The post-natal evaluation confirmed that half the patients had urinary calculus disease. CONCLUSION: Ureteric stenting during pregnancy can be safe, with no intraoperative imaging and even under local anaesthesia. It provides good symptom relief and has a low complication rate. We therefore advocate it as a first-line treatment in pregnant women with therapy-resistant flank pain. PMID- 26558074 TI - The effect of preoperative clinical variables on the 30- and 90-day morbidity and mortality after radical cystectomy: A single-centre study. AB - OBJECTIVE: To analyse the effect of preoperative clinical variables and comorbidity on the early, late and cumulative 90-day morbidity and mortality rates, as well as hospital re-admissions, after radical cystectomy (RC), in one centre. PATIENTS AND METHODS: All patients undergoing RC over a period of 3 months were included. Preoperative investigations included measurements of serum albumin, a complete blood analysis, body mass index (BMI), Charlson comorbidity index (CCI) and the age-adjusted CCI (ACCI). We recorded the length of hospital stay (LOS) and all postoperative events for 90 days, and graded them according to the five-grade modification of the original Clavien system. RESULTS: In all there were 31 patients undergoing RC (mean age 58.4 years). The mean preoperative serum albumin and haemoglobin level, BMI, CCI and ACCI were 3.82 g/dL, 12.53 g/dL, 29.29 kg/m(2), 3.0 and 4.58, respectively. The mean LOS was 20.03 days; seven patients needed re-admission and three died within the 90 days. There were postoperative complications in 20 patients. The age, CCI and ACCI were significantly associated with complications (P = 0.009, 0.001 and < 0.001, respectively). Preoperative haemoglobin, BMI and smoking had no effect on the morbidity or mortality rate. The LOS increased in older patients (P = 0.031) and those with a higher ACCI (P = 0.042). Postoperative mortality increased among patients with a lower serum albumin level (P = 0.048). CONCLUSIONS: Age, CCI and ACCI are related to early postoperative complications. Older patients and patients with a higher ACCI have a longer LOS. A low preoperative albumin level needs to be evaluated more thoroughly. PMID- 26558075 TI - Leiomyosarcoma of the urinary bladder: A review and a report of two further cases. AB - OBJECTIVES: To review the published cases of leiomyosarcoma of the urinary bladder and to report two further cases. METHODS: The databases Pubmed and Hinari were searched using the keywords 'bladder', 'leiomyosarcoma' and 'smooth muscle neoplasm'. The 14 articles identified were reviewed, and we present a further two cases. RESULTS: Of more than 100 cases reported, 77 were reviewed. There is a lack of consensus about the standard treatment, and little is known about the natural history and prognosis of the tumour, due to its very low incidence. These tumours occur in older adults of either sex and are characterised by an aggressive behaviour. There is usually an unfavourable outcome, with the lungs being the most common site of metastasis. The two further cases we report had a different presentation and outcome. CONCLUSIONS: Because of the limited experience with this rare tumour, there are insufficient data to suggest the optimum management strategy and prognosis. PMID- 26558076 TI - Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers. AB - OBJECTIVES: To evaluate the role of smoking as a risk factor for higher stages and grades of bladder cancer, for although smoking is considered to be one of the most important risk factors for bladder cancer, its relationship to grade and stage is not clear. PATIENTS AND METHODS: In all, 300 patients diagnosed with bladder cancer were studied to compare the grade and stage and bladder cancer between non-smokers, low-dose, moderate-dose and high-dose smokers. RESULTS: The smokers and non-smokers had no significant difference in tumour grade or stage (P = 0.702 for grade and 0.166 for stage) but the high-dose group had significantly higher grades and stages than the other groups (P = 0.026, odds ratio 4.8, 95% confidence interval 1.2-19.1 for grade, and 0.037, 10.91 and 1.16-102.6, respectively, for stage). CONCLUSION: Smoking has a potential dose-dependent effect on the grade and stage of bladder cancer, with high-dose smokers having more aggressive disease. The equality in the aggressiveness of the cancer between smokers in general and non-smokers might be a result of the hazardous effect of passive smoking in countries where smoking is a common habit. PMID- 26558077 TI - The use of an acellular collagen matrix in penile augmentation: A pilot study in Saudi Arabia. AB - OBJECTIVES: To assess the use of an acellular collagen matrix (Pelvicol, Bard Medical, Covington, GA, USA), a successful agent for reconstructive surgery, for enhancing penile girth. PATIENTS AND METHODS: Between June and December 2011, 18 patients (mean age 24 years, range 19-38) had their penis augmented with Pelvicol; the mean (range) penile circumference was 9.2 (7-13) cm before treatment. They were divided into two groups; the first (10 patients) had a Pelvicol sheet of 8 * 12 cm inserted through a V-Y suprapubic incision and wrapped around the shaft in a bilayer under the dartos fascia, but not covering the urethra, with division of the suspensory ligament. The second group of eight patients had the Pelvicol inserted through a subcoronal degloving incision and placed in one layer. The penile circumference was measured at 6 and 12 months after surgery. Patient satisfaction at 1 year after surgery was assessed as 'poor', 'unsatisfied', 'moderately satisfied', 'highly satisfied', or 'excellent'. RESULTS: The mean (range) increase in girth (circumference) was 2.8 (2-3.2) cm in group 1 and 1.7 (1.2-2) cm in group 2. In group 1, two patients were highly satisfied, four moderately satisfied and four unsatisfied; in group 2, three were moderately satisfied and five unsatisfied. Complications were common in both groups, with five patients in group 1 and three in group 2 developing severe penile oedema and ischaemic shaft ulcers. Removal of the graft was required in two patients in each group. CONCLUSION: This pilot study shows that Pelvicol is not an ideal option for enhancing penile girth, and the method of placement did not apparently influence the result. PMID- 26558078 TI - Single- vs. multi-stage repair of proximal hypospadias: The dilemma continues. AB - INTRODUCTION: The surgical reconstruction of distal penile hypospadias in a single stage is the standard practice for managing anterior hypospadias. Unfortunately, it is not simple to extrapolate the same principle to proximal hypospadias. There is no consensus among hypospadiologists about whether a single or multi-stage operation is the optimal treatment for proximal hypospadias. In this review, we assess the currently reported outcomes and complications of both techniques in proximal hypospadias repair. METHODS: We searched Medline, Pubmed, Scopus and Ovid for publications in the last 10 years (2002-2012) for relevant articles, using the terms 'proximal hypospadias', 'posterior hypospadias' 'single stage', 'multiple stage', and 'complications'. Articles retrieved were analysed according to the technique of repair, follow-up, complications, success rate, number of included children, and re-operative rate. RESULTS AND CONCLUSIONS: The reported complications in both techniques were similar, including mostly minor complications in the form of fistula, meatal stenosis, partial glans dehiscence, and urethral diverticulum, with their easy surgical repair. The outcomes of single- and multistage repairs of proximal hypospadias are comparable; no technique can be considered better than any other. Thus, it is more judicious for a hypospadiologist to master a few of these procedures to achieve the best results, regardless of the technique used. PMID- 26558079 TI - Down-regulated claudin-7 immunoexpression in urothelial carcinoma of the urinary bladder. AB - OBJECTIVES: To analyse the gene-expression level of claudin-7 in urothelial carcinoma (UC) of the urinary bladder, and its relationship with clinicopathological variables. MATERIALS AND METHODS: This study included 68 specimens of UC of the bladder, comprising 35 with non-muscle-invasive (NMI), stage Ta-T1, and 33 with muscle-invasive (MI) tumours, T2-T4, and 26 of normal urothelium (NU). Total RNA was extracted and 1 MUg was reverse transcribed using a cDNA kit. RT-PCR was conducted using SYBR Green I dye to examine the expression levels of the target gene (claudin-7) and the housekeeping gene glyceraldehyde-3 phosphate dehydrogenase. Using confocal-laser scanning light microscopy, immunohistochemistry (IHC) was used to validate the RT-PCR data. The correlation between claudin-7 and the clinicopathological variables was assessed. RESULTS: Claudin-7 was down-regulated in UC samples compared to NU samples (P < 0.001). NMI (Ta-T1) tumours had significantly higher claudin-7 expression than MI (?pT2) tumours (P = 0.012). There was no significant difference between patients with G1 2 tumours and those with G3 tumours (P = 0.19). There was no significant difference between patients with recurrent NMI UC and those with no recurrence (P = 0.61). IHC showed a lower expression of claudin-7 in the UC samples than NU samples, and in MI UC than in NMI UC. CONCLUSIONS: These results indicate that a reduced expression of claudin-7 correlates with the invasiveness and progression of UC of the urinary bladder. Further studies are needed to validate claudin-7 as a marker for UC. PMID- 26558080 TI - Inhibition of calcium oxalate crystallisation in vitro by an extract of Bergenia ciliata. AB - OBJECTIVE: To evaluate the effectiveness of an extract obtained from the rhizomes of Bergenia ciliata (Saxifragaceae) on the inhibition of calcium oxalate (CaOx) crystallisation in vitro. MATERIALS AND METHODS: A hydro-alcoholic extract (30:70, v/v) of rhizomes of B. ciliata was prepared at different concentrations (1-10 mg/mL). The crystallisation of CaOx monohydrate (COM) was induced in a synthetic urine system. The nucleation and aggregation of COM crystals were measured using spectrophotometric methods. The rates of nucleation and aggregation were evaluated by comparing the slope of the turbidity of a control system with that of one exposed to the extract. The results were compared with a parallel study conducted with a marketed poly-herbal combination, Cystone, under identical concentrations. Crystals generated in the urine were also analysed by light microscopy. Statistical differences and percentage inhibitions were calculated and assessed. RESULTS: The extract of B. ciliata was significantly more effective in inhibiting the nucleation and aggregation of COM crystals in a dose-dependent manner than was Cystone. Moreover, the extract induced more CaOx dihydrate crystals, with a significant reduction in the number and size of COM crystals. CONCLUSION: An extract of the traditional herb B. ciliata has an excellent inhibitory activity on crystalluria and therefore might be beneficial in dissolving urinary stones. However, further study in animal models of urolithiasis is needed to evaluate its potential anti-urolithiatic activity. PMID- 26558081 TI - [Not Available]. PMID- 26558082 TI - Sexual dysfunction in 2013: Advances in epidemiology, diagnosis and treatment. AB - OBJECTIVES: To provide a contemporary review of the epidemiology, diagnosis and treatment of premature ejaculation (PE) and erectile dysfunction (ED). METHODS: We searched for English-language articles published in the past 12 months using the PubMed database. Relevant articles on the subjects of sexual dysfunction, ED and PE were selected for review. CONCLUSIONS: Recent studies on male sexual dysfunction have provided new therapeutic possibilities. Tramadol, a well-used analgesic, has a new role in the treatment of PE. Super-selective targeting of dorsal penile nerves by surgery or cryoablative technologies might become a viable treatment option for refractory PE in the future. The role of ED as a harbinger of important comorbidities allows for the early detection and intervention of these conditions, which can optimise therapeutic outcomes. The long-term effect of chronic phosphodiesterase-5 inhibitors on endothelial dysfunction, the angiogenic potential of low-intensity extracorporeal shock wave therapy, and further advances in drug-eluting endovascular stents might in future allow clinicians to treat ED more definitively. PMID- 26558084 TI - Erectile dysfunction and cardiovascular disease. AB - The link between erectile dysfunction (ED) and cardiovascular disease (CVD) is reviewed by assessing original papers, current consensus, previous reviews and meta-analyses. The link between these conditions is confirmed, and the evaluation and assessment summarised with a new evidence-based algorithm. ED, especially in younger men, is a marker of an increased risk of CVD, and ED needs to be incorporated into all risk-screening programmes. PMID- 26558083 TI - Is erectile dysfunction a reliable indicator of general health status in men? AB - INTRODUCTION: Erectile dysfunction (ED) is a common risk factor in men and its incidence increases with age. Ageing and older men frequently have comorbidities such as cardiovascular diseases (CVD), diabetes mellitus (DM), hypertension, chronic obstructive pulmonary disease and dyslipidaemia; likewise, they concurrently refer to a clinician for impairments in sexual function, mostly for ED. The association of ED and other organic, multi-organic or even systemic diseases is widely described, with a specific emphasis on the fact that they often share common pathophysiological factors and mechanisms. Thus we reviewed previous reports assessing the role of ED as a sentinel marker of overall men's health. DISCUSSION: ED is considered an important sentinel marker for CVD. Numerous studies have highlighted the predictive role of ED for subsequent CV events in patients with a silent history of coronary artery disease. Indeed, ED might be considered as a clinical manifestation of a generalised vascular disease, and it should provoke clinicians to check for CVDs in those patients complaining of impaired erectile function. This concept appears to be even more important for men with DM, where ED has already been shown to have a significant predictive ability for major vascular complications. Moreover, data from large population-based studies showed that ED is a significant predictor of all-cause mortality, in addition to CV outcomes. The severity of erectile function is assessed with the International Index of Erectile Function-Erectile Function domain score, and this has emerged as a proxy for men's general health status, as assessed with the Charlson Comorbidity Index score. CONCLUSIONS: Patients complaining of ED should be evaluated with a comprehensive medical and sexual history, and a thorough physical examination, regardless of their age, considering ED as an opportunity to screen for the presence of health-threatening concomitant comorbidities. PMID- 26558085 TI - Psychological and interpersonal dimensions of sexual function and dysfunction. AB - INTRODUCTION: Sex therapy techniques comprise behavioural and cognitive as well as psychodynamic and educational interventions, like reading ('bibliotherapy'), videotapes and illustrations of anatomical models. Contemporary approaches focus on desire, pleasure and satisfaction. DISCUSSION: It is important to assess medical and biological factors involved in the genesis of sexual dysfunctions. Sex therapy techniques were developed by Masters and Johnson, and their premise was to eliminate 'performance anxiety' by emphasising the undemanding nature of the sexual relation. New methods were introduced, like Internet-administered techniques, and 'mindfulness therapy', and they proved to be effective. CONCLUSIONS: Psychological treatments have some relieving effects on sexual dysfunction, but for studies of the outcomes it is difficult to meet the requirements of evidence-based medicine. PMID- 26558086 TI - Phosphodiesterase type 5 inhibitors as a treatment for erectile dysfunction: Current information and new horizons. AB - INTRODUCTION: Over the past 15 years, the discovery and development of oral medications that selectively inhibit the enzyme phosphodiesterase type 5 (PDE5) have revolutionised the treatment of erectile dysfunction (ED). Currently, three PDE5 inhibitors are widely available clinically, i.e., sildenafil, vardenafil and tadalafil. New PDE5 inhibitors, including avanafil and udenafil, are now in clinical use in a few countries, and other compounds are under development. METHODS: We describe the current use and future direction of PDE5 inhibitors in the treatment of ED. RESULTS AND CONCLUSION: Each PDE5 inhibitor has an excellent and comparable efficacy and tolerability. These drugs are highly effective for ED of various causes, and are effective in preventing ED after radical prostatectomy. However, whilst being at least 60% effective, PDE5 inhibitors are still ineffective in at least 30% of patients, prompting current research into other pharmacological targets for ED. PMID- 26558087 TI - Current penile-rehabilitation strategies: Clinical evidence. AB - We review the current strategies used for penile rehabilitation (PR) after a radical prostatectomy, where PR is defined as the attempt to restore spontaneous erectile function so that the patient can generate erections with no need for erectile aids. We searched PubMed for relevant reports, using the keywords 'radical prostatectomy', 'penile rehabilitation', 'phosphodiesterase inhibitors', 'vacuum erection device', 'injection therapy', 'urethral suppository', and 'erectile dysfunction'. In all, 155 articles were identified and reviewed, and had a level of evidence ranging from 1b-4. The use of PR strategies should be based on the patient's goals after a thorough explanation of realistic expectations, and the risks and consequences of the various treatment options. While a multitude of studies suggest a benefit with PR strategies, there are no established, proven regimens. Further research is needed to establish the optimal approaches to PR. PMID- 26558088 TI - Stem-cell therapy for erectile dysfunction. AB - INTRODUCTION: Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause. Recently, therapies based on stem cells (SCs) have had an increasing attention for their potential to restore erectile function. Preclinical studies showed that these cells might reverse the pathophysiological changes leading to ED, rather than treating the symptoms of ED. This review is intended to provide an overview of contemporary reports on the use of SCs to treat ED. METHODS: We made an extensive search for reports on SC-based therapy for the management of ED, published in English between 1966 and 2013, using the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar and Pubmed, with the search terms 'erectile dysfunction', 'stem cells', 'multipotent stromal cells', 'adipose (tissue) derived stem cells', 'bone-marrow derived stem cells', 'animal model', 'diabetes', 'ageing', 'Peyronie's Disease' and 'cavernous nerve injury'. RESULTS: Fifty-four papers were identified and contributed, either as an original research report or review thereof, to this review. Several preclinical studies addressed SC-based therapies for the recovery of erectile function caused by a variety of both chronic and acute conditions. Overall, these studies showed beneficial effects of SC therapy, while evidence on the mechanisms of action of SC therapy varied between studies. One clinical trial investigated the short-term effects of SC therapy in diabetic patients with ED. Two more clinical trials are currently recruiting patients. CONCLUSIONS: The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED. PMID- 26558089 TI - Penile prosthesis surgery in the management of erectile dysfunction. AB - INTRODUCTION: We reviewed retrospectively the use of penile prostheses, including the indications and complications of penile prosthesis surgery. METHODS: We identified publications and the reported advances in penile prosthesis surgery between 1987 and 2012 in Pub-Med, and published information from American Medical Systems, Inc. (Minnetonka, MN, USA) and Coloplast Corporation (Humlebaek, Denmark), using the keywords 'penile prosthesis', 'erectile dysfunction', 'mechanical reliability', 'complications' and 'infection'. RESULTS: We describe the novel indications for the use of penile prostheses, the significant advances in implant designs with improved mechanical reliability, the changing landscape of device infection, and the current management of complications. Sixty-eight publications with a grade A, B and C level of evidence are cited. CONCLUSION: The clinical indications to implant a penile prosthesis have expanded beyond organic erectile dysfunction. With the many different devices currently available, the choice of which device to implant can be tailored based on an individual's unique medical conditions, manual dexterity and expectations, and surgeon preference. There must be a conscious effort to prevent device infection, in the light of the development of increasingly virulent organisms. Penile prosthesis surgery is an integral part of the treatment of erectile dysfunction when non-surgical options fail or are contraindicated. PMID- 26558090 TI - Penile vascular surgery for treating erectile dysfunction: Current role and future direction. AB - Penile vascular surgery for treating erectile dysfunction (ED) is still regarded cautiously. Thus we reviewed relevant publications from the last decade, summarising evidence-based reports consistent with the pessimistic consensus and, by contrast, the optimistically viable options for vascular reconstruction for ED published after 2003. Recent studies support a revised model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360 degrees complete inner circular layer and a 300 degrees incomplete outer longitudinal coat. Additional studies show a more sophisticated venous drainage system than previously understood, and most significantly, that the emissary veins can be easily occluded by the shearing action elicited by the inner and outer layers of the tunica albuginea. Pascal's law has been shown to be a significant, if not the major, factor in erectile mechanics, with recent haemodynamic studies on fresh and defrosted human cadavers showing rigid erections despite the lack of endothelial activity. Reports on revascularisation surgery support its utility in treating arterial trauma in young males, and with localised arterial occlusive disease in the older man. Penile venous stripping surgery has been shown to be beneficial in correcting veno-occlusive dysfunction, with outstanding results. The traditional complications of irreversible penile numbness and deformity have been virtually eliminated, with the venous ligation technique superseding venous cautery. Penile vascular reconstructive surgery is viable if, and only if, the surgical handling is appropriate using a sound method. It should be a promising option in the near future. PMID- 26558091 TI - Penile reconstruction in the male. AB - We describe and review the most recent techniques of male genital reconstruction, identifying relevant material with an unstructured PubMed-based search of previous reports, using the keywords 'reconstruction', 'glans', 'shaft', 'lymphoedema', 'skin graft', 'scrotoplasty', 'urethroplasty', and 'penile prosthesis'. This search produced 22 reports that were analysed in this review. Split-thickness skin grafts are ideal for glans reconstruction, while full thickness skin grafts should be used to cover defects on the shaft penis, as they tend to heal with less contracture. The radial artery-based free-flap phalloplasty is the technique of total phallic reconstruction associated with the highest satisfaction rates. Further research is required to identify an ideal reconstructive technique that would guarantee superior cosmetic and functional results, minimising donor site morbidity. PMID- 26558092 TI - The pathophysiology of Peyronie's disease. AB - OBJECTIVE: To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). METHODS: Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. RESULTS: More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. CONCLUSION: PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease. PMID- 26558093 TI - Peyronie's disease: A contemporary review of non-surgical treatment. AB - In this review I discuss the current non-surgical treatment options for Peyronie's disease (PD), which remains a therapeutic dilemma for the treating physician. This is despite a large array of treatments that have been used since the time of de la Peyronie in the mid-18th century. Part of the problem with finding an effective treatment is the incomplete understanding of the aetiopathophysiology of this scarring disorder. Published articles in peer reviewed journals were assessed, recognising that most of the reported trials are compromised by being single-centre studies with no placebo control. Various treatment options have emerged, most with limited and unreliable benefit, but a few treatments have shown a consistent, albeit incomplete, response rate. Currently the only scientifically sensible oral agents appear to be pentoxifylline, l-arginine, and possibly the phosphodiesterase type-5 inhibitors. The current intralesional injection treatment options include verapamil and interferon, with a reported benefit in reducing deformity and improving sexual function. Intralesional clostridial collagenase is in the midst of phase-3 trial analysis by the USA Food and Drug Administration. External mechanical traction therapy has recently emerged as a technique to reduce the curvature, recover lost length, and possibly obviate surgery. Currently there is no clear, reliable and effective non-surgical treatment for PD, but it appears that several of the available treatments can reduce the deformity and improve sexual function, and might at least stabilise the disease process. PMID- 26558094 TI - A critical analysis of the surgical outcomes for the treatment of Peyronie's disease. AB - Peyronie's disease (PD) is a relatively common condition, which can impair sexual function and result in emotional and psychological distress. Despite an abundance of minimally invasive treatments, few have confirmed efficacy for improving penile curvature and function. Surgical therapies include many different techniques and are reserved for patients with stable disease of ?12 months' duration. We searched PubMed for all articles from 1990 to the present relating to the surgical management of PD. Preference was given to recent articles, larger series, and those comparing various techniques and/or materials. Outcomes were subsequently analysed and organised by surgical technique and the graft material used. Available surgical techniques include plication/corporoplasty procedures, incision and grafting (I&G), and placing a penile prosthesis with or without adjunctive procedures. Although several surgical algorithms have been reported, in general, plication/corporoplasty procedures are reserved for patients with adequate erectile function, simple curvatures of <60 degrees , and with no deformities (hour-glass, hinge). I&G are reserved for complex curvatures of >60 degrees and those with deformities. Penile prostheses are indicated for combined erectile dysfunction and PD. Overall outcomes show high rates of improved curvature and patient satisfaction, with mildly decreased erectile function with both plication and the I&G procedure (I&G >plication) and decreases in penile length (plication >I&G). Surgical management of PD remains an excellent treatment option for patients with penile curvature precluding or impairing sexual activity. Surgical algorithms are available to assist treating clinicians in appropriately stratifying surgical candidates. Additional research is needed to identify optimal surgical techniques and materials based on patient and disease characteristics. PMID- 26558095 TI - Treatments for fibrosis of the corpora cavernosa. AB - INTRODUCTION: Corporal fibrosis usually occurs after explantation of an infected penile prosthesis, severe penile trauma, refractory low-flow priapism, Peyronie's disease, or the chronic intracavernous injection of vasoactive drugs. METHODS: We analysed current treatmentss for penile fibrosis. We searched PubMed using the keywords 'penile corporal fibrosis', 'treatment' and 'penile fibrosis', resulting in 63 matches, of which 19 articles met the inclusion criteria. RESULTS AND CONCLUSIONS: This review covers conservative medical therapy for corporal fibrosis and surgical therapeutic methods. The roles of phosphodiesterase- 5 inhibitors and pentoxifylline are analysed. Surgical therapy includes implantation of a penile prosthesis and corporal reconstruction, and these are reviewed. Corporal fibrosis is a major problem for patients, and is associated with severe erectile dysfunction. Conservative treatment options can be applicable in the early phase, but simultaneous corporal reconstruction procedures with concomitant implantation of a penile prosthesis should be attempted in severe cases of corporal fibrosis. PMID- 26558096 TI - Psychological and interpersonal dimensions of sexual function and dysfunction in women: An update. AB - INTRODUCTION: We reviewed the psychological and interpersonal dimensions of female sexual function and dysfunction. METHODS: We identified articles published in 1970-2013 using the keywords 'female sexual dysfunction', 'sexual desire', 'sexual arousal', 'female orgasmic disorder', 'sex therapy', 'psychotherapy', 'behaviour therapy' and 'Internet therapy'. Over 200 articles were reviewed (Level of evidence 2b). RESULTS AND CONCLUSIONS: We identified the major psychological variables affecting female sexual function. The outcomes of psychological treatment interventions are reported. A collaboration between healthcare practitioners from different disciplines is necessary in the evaluation, treatment and education of female patients with sexual dysfunction. The assessment of female and couples' sexual dysfunction should ideally include an enquiry about the predisposing, precipitating, maintaining and contextual factors. PMID- 26558097 TI - Integrating psychotherapy and pharmacotherapy in the treatment of premature ejaculation. AB - OBJECTIVES: To describe the different approaches to the treatment of premature ejaculation (PE), with a final focus on integrated treatment, as conventional theories and therapies for PE are based on an organic or psychogenic dichotomy. METHODS: We list the principal hypotheses of the causes and therapy of PE on the basis of psychological and medical perspectives, after identifying all relevant studies available on Medline up to 2012. RESULTS: The cognitive feedback from PE can lead to a 'performance anxiety', which can combine with other conditions to further impair ejaculatory control. For these reasons, a psychological approach is always useful in treating PE, the most useful of which are sex therapy and behavioural therapy. For pharmacological treatment, reports suggest that dapoxetine (60 mg) significantly improves the control of the ejaculatory reflex, and it thus represents the first-line officially approved pharmacotherapy for PE. CONCLUSIONS: A holistic approach which considers the biological, psychological and relational aspects is the advised treatment for PE. Integrated medical and psycho-sexological therapy requires a mutual understanding of and respect for the different disciplines involved in sexology. In this aspect two very important roles are those of the physician and the psychologist. PMID- 26558098 TI - Overactive bladder syndrome: Current pathophysiological concepts and therapeutic approaches. AB - OBJECTIVES: The overactive bladder syndrome (OAB) is a highly prevalent and bothersome symptom complex. We review contemporary reports to provide an update of the key aspects of its pathogenesis and the therapeutic approaches. METHODS: The PUBMED database was searched for relevant publications in the period from 1 January 1985 to 1 May 2013, using the keywords 'overactive bladder', 'anti muscarinics', 'beta-3 agonists', 'intravesical botulinum toxin', 'tibial nerve stimulation and 'sacral neuromodulation'. RESULTS: In all, 33 articles were selected for this review. OAB is very common, affecting 10-20% of the population. It is often bothersome and frequently affects the quality of life. The current definition of OAB remains a source of controversy. Anti-muscarinic agents remain the mainstay of pharmacotherapy. The new beta-3 agonists have some efficacy whilst avoiding anti-cholinergic effects, and so might benefit patients who are unable to tolerate anti-muscarinic agents. Intravesical botulinum toxin is recommended for patients in whom oral pharmacotherapy fails, although the optimal parameters in terms of dosing, number of injections and injection site are yet to be fully established. Sacral neuromodulation is another option that has a good response in about half of patients. CONCLUSIONS: OAB remains an incompletely understood problem that presents a significant management challenge. A range of therapeutic options is now available for clinicians managing this problem. PMID- 26558099 TI - Voiding dysfunction in women: How to manage it correctly. AB - INTRODUCTION: Of women aged >40 years, 6% have voiding dysfunction (VD), but the definition for VD in women with respect to detrusor underactivity (DU) and bladder outlet obstruction (BOO) is not yet clear. In this review we address the current literature to define the diagnosis and treatment of VD more accurately. METHODS: We used the PubMed database (1975-2012) and searched for original English-language studies using the keywords 'female voiding dysfunction', 'detrusor underactivity', 'acontractile detrusor' and 'bladder outlet obstruction and urinary retention in women'. We sought studies including the prevalence, aetiology, pathogenesis, diagnosis and treatment of female VD. RESULTS: In all, 20 original studies were identified using the selected search criteria, and another 45 were extracted from the reference lists of the original papers. All studies were selected according to their relevance to the current topic and the most pertinent reports were incorporated into this review. CONCLUSION: Female VD might be related to DU or/and BOO. Voiding and storage symptoms can coexist, making the diagnosis challenging, with the need for a targeted clinical investigation, and further evaluation by imaging and urodynamics. To date there is no universally accepted precise diagnostic criterion to diagnose and quantify DU and BOO in women. For therapy, a complete cure might not be possible for patients with VD, therefore relieving the symptoms and minimising the long-term complications associated with it should be the goal. Treatment options are numerous and must be applied primarily according to the underlying pathophysiology, but also considering disease-specific considerations and the abilities and needs of the individual patient. The treatment options range from behavioural therapy, intermittent (self-)catheterisation, and electrical neuromodulation and neurostimulation, and up to urinary diversion in rare cases. PMID- 26558100 TI - Male incontinence and the transobturator approach: An analysis of current outcomes. AB - OBJECTIVES: To provide an analysis of the outcomes in patients who have a suburethral sling placed using the transobturator approach for the treatment of stress urinary incontinence after radical prostatectomy, because data in this specific area remain limited, and recent changes in male sling surgery might improve the efficacy in men with moderate or mild incontinence. METHODS: We evaluated the results of transobturator non-adjustable and re-adjustable sling systems after reviewing previous reports identified using the Medline and PubMed databases for original articles, from 2002 to 2012, using the terms 'postoperative male incontinence', 'transobturator' and 'male sling'. Of a total of 31 articles, we reviewed the 22 related to the outcomes of the suburethral sling with positioning by the transobturator approach. RESULTS: Currently the only results of the transobturator approach are those relating to the AdVanceTM device (American Medical Systems, Minnetonka, MN, USA), for which the cure rate is ~ 60% at 20 months. The remaining devices, although innovative, were assessed in studies for which the follow-up was too short to make a judgement. CONCLUSIONS: It would be advisable to reserve the transobturator approach for patients with mild and moderate incontinence, and refer those with severe incontinence, with or without adjuvant radiotherapy after radical prostatectomy, for treatment with an artificial urinary sphincter. More results and a long-term follow-up are needed to evaluate the effectiveness of these devices. PMID- 26558101 TI - Detrusor after contractions in men with lower urinary tract symptoms: Myth or reality? AB - OBJECTIVES: To study after contractions in men with lower urinary tract symptoms (LUTS) related to bladder outlet obstruction (BOO), in the absence of neuropathy, and to verify whether it is associated with the severity of symptoms or certain filling and voiding variables. PATIENTS AND METHODS: Of 380 patients with LUTS and who were assessed using urodynamic studies, we retrospectively analysed those who had after contractions (ACs). Bladder overactivity was diagnosed as any increase in the detrusor pressure of <2-s duration during the filling phase, and an AC was diagnosed as any increase in the detrusor pressure of ?2 s after the end of the voiding phase and complete cessation of flow. The presence of ACs was then assessed in relation to different components of the International Prostate Symptom Score (IPSS), using a two-tailed Levene's test, and to filling and voiding cystometry variables, using Mann-Whitney-Wilcoxon Rank test. RESULTS: In all, 373 of the 380 patients were included (seven had invalid voiding cystometry); ACs were detected in 51 (13.9%). There was no statistical significance for associations between AC and any of the variables assessed, including individual questions of the IPSS, detrusor overactivity, cystometric capacity, compliance, maximum urinary flow rate (Qmax), detrusor pressure at Qmax or the maximum detrusor voiding pressure. CONCLUSION: ACs detected on voiding cystometry of men with LUTS attributed to BOO do not seem to be related to symptoms, or filling and voiding variables. PMID- 26558102 TI - A quantitative comparison between free uroflow variables and urodynamic data, and the effect of the size of urodynamic catheters on its interpretation. AB - OBJECTIVE: To assess the effect of the urodynamic catheter on the urinary flow rate and residual volume in various urodynamic diagnoses, and compare the outcome when using a smaller catheter, as the effect of this catheter on free uroflow variables is mostly studied in patients with bladder outlet obstruction (BOO) and little is known about its effect in other urodynamic diagnoses. PATIENTS AND METHODS: In all, 319 men undergoing a pressure-flow study (PFS) with a 5 F filling and 5 F measuring bladder catheter were subdivided into three groups based on a urodynamic diagnosis, i.e. normal PFS (group 1), BOO (group 2) and detrusor underactivity (DU, group 3). Another group (4) comprised 61 patients who had a PFS with the filling catheter removed before the voiding phase. The effect of the catheters on the maximum urinary flow rate (Qmax) and the postvoid residual volume (PVR) was analysed statistically and compared among the groups. We also compared the free-flow variables with the clinical and urodynamic variables. RESULTS: Groups 1-3 (with two catheters) had a significantly lower Qmax and higher PVR than those voiding with one catheter (group 4). The reduction in Qmax was highest in group 3 (41.9%) and least in group 2 (21%). Group 4 showed no significant change in Qmax in cases with BOO and a normal PFS but a significant decline in those with DU (19.6%). The PVR was positively associated with the bladder capacity and negatively with detrusor contractility, but no association with a urodynamic diagnosis of BOO or any specific symptom. CONCLUSION: Detrusor contractility was the strongest predictor of the obstructive effect caused by the catheter. This study justifies the use of a single 5 F catheter at the time of voiding, although that can also cause a reduction in flow in patients with DU. PMID- 26558103 TI - The satisfaction of patients with refractory idiopathic overactive bladder with onabotulinumtoxinA and augmentation cystoplasty. AB - OBJECTIVE: To assess the satisfaction of patients with refractory idiopathic overactive bladder (OAB) with two treatment methods, onabotulinumtoxinA (oBTX) and augmentation ileocystoplasty (AC). PATIENTS AND METHODS: This prospective study included patients with refractory idiopathic OAB for >6 months and a urodynamic diagnosis of OAB. Oral pharmacotherapy had failed in all patients. Patients with any suspected neurological disorder were excluded. Before the procedure, patients completed the Urogenital Distress Inventory (UDI-6) and modified Incontinence Impact Questionnaire (IIQ-7), a neurological evaluation, a urodynamic study and their postvoid residual urine volume was measured. Patients were assigned to receive oBTX or AC, depending on patient's preference. Follow-up visits were at 6 weeks and 3 and 6 months after the procedure. The OAB Satisfaction questionnaire (OAB-SAT-q) was used to assess satisfaction after the procedure. RESULTS: In all, 31 patients with refractory OAB were included, 16 in the oBTX group and 15 in the AC group. There was no significant difference between the groups in mean age, baseline OAB symptoms and urodynamic values. There were significant improvements in urinary symptoms (UDI-6) and quality of life (IIQ-7) after both procedures (except in the domain enquiring about difficulty, which significantly worsened after AC). Of the 16 patients, 15/16 and seven of 15 were completely dry after AC and oBTX, respectively. The overall and individual scores of the OAB-SAT-q were significantly higher among patients treated with AC than with oBTX. The incidence of the de novo need to use clean intermittent catheterisation after oBTX and AC was two of 16 and four of 15, respectively. CONCLUSIONS: Both procedures are effective in improving the symptoms of OAB and of quality of life, but patients were more satisfied with AC than oBTX therapy. PMID- 26558104 TI - The advantages of the ventral approach to bulbar urethroplasty. AB - BACKGROUND: Several surgical techniques have been described for the treatment of bulbar urethral strictures, and the main goal of modern surgery is to reduce morbidity and obtain the best outcome with the fewest complications. Currently, the superiority of one surgical technique over another has not yet been clearly defined. METHODS: We analysed the historical background, advantages and disadvantages of several urethral approaches and graft placements, with the aim of focusing on the advantages of the ventral approach. CONCLUSIONS: For short bulbar strictures (<2 cm) the traditionally advocated method is excision and end to-end anastomosis, whilst for longer strictures, in the last decade, the patch graft urethroplasty has been used, with buccal mucosa advocated as the standard material of substitution. Our analysis showed that the approach (dorsal vs. ventral) to the bulbar urethral lumen and the location of the patch (dorsal vs. ventral) are contentious issues. Overall, surgeons tend to use techniques that are easy, quick and give excellent outcomes with few complications. The graft urethroplasty using the ventral approach fulfils these requirements. PMID- 26558106 TI - Statistical superiority sometimes makes little clinical sense. PMID- 26558105 TI - The role of an abnormal prostate-specific antigen level and an abnormal digital rectal examination in the diagnosis of prostate cancer: A cross-sectional study in Qatar. AB - OBJECTIVE: To investigate the role of an abnormal prostate-specific antigen (PSA) level and abnormal findings on a digital rectal examination (DRE) in the detection of prostate cancer in men in Qatar. PATIENTS AND METHODS: Between June 2008 and September 2012, 651 patients had a transrectal ultrasonography-guided biopsy of the prostate (TRUSBP) at our centre. The indications for a biopsy were a high PSA level (>4 ng/mL), or an abnormal DRE result. Patients were assessed by a thorough history, clinical examination and routine laboratory investigations. Data, including age, DRE findings, TRUS findings, total PSA level, prostate volume and the pathology results, were evaluated. RESULTS: The mean (SD) age of the 651 patients was 64.1 (7.4) years. Prostate cancer was detected in 181 men (27.8%), benign prostatic hyperplasia in 275 (42.2%) and prostatitis in 236 (36.4%). The sensitivity and specificity for detecting prostate cancer were 93.9% and 8.5% for an abnormal PSA level (>4 ng/mL), 46.1% and 84.7% for abnormal DRE findings, and 95% and 30.2% for the two combined. Using a receiver operating characteristics curve, a PSA threshold of 7.9 ng/mL had a sensitivity of 56.6% and specificity of 52.8%. When a PSA threshold of 7.9 ng/mL was used in combination with abnormal DRE findings, the overall accuracy was 76.9%. CONCLUSION: The PSA threshold level of 7.9 ng/mL, determined by this analysis, has a higher likelihood of detecting prostate cancer in men in Qatar. However, it failed to detect cancer in substantially many men with statistically significant disease. PMID- 26558107 TI - Transvesical open prostatectomy for benign prostatic hyperplasia in the era of minimally invasive surgery: Perioperative outcomes of a contemporary series. AB - OBJECTIVE: To assess the perioperative morbidity of transvesical open prostatectomy (OP) and its predictors as a treatment for benign prostatic hyperplasia (BPH), and to update knowledge about the morbidity of OP using a standardised morbidity scale (Clavien), thus providing a platform for comparison with the newly developed techniques. PATIENTS AND METHODS: We retrospectively review men with BPH who were treated with transvesical OP between April 2002 and December 2012. Preoperative patients' data were reviewed for relevant variables. Operative details, the postoperative course, and 30-day relevant data were assessed. The study cohort was stratified based on the resected prostate weight, with group 1 having a resected weight of ?120 g and group 2 >120 g. RESULTS: The review identified 163 patients. The mean (SD, range) duration of catheterisation after OP was 7.9 (2.2, 5-20) days and the duration of hospitalisation after OP was 8.1 (1.8, 5-15) days; both were significantly longer in group 2. All patients were able to void spontaneously by the first follow-up visit. Of 163 OP procedures, there were 106 perioperative complications in 69 (42.3%). Low-grade complications (grade ?2) included 38 (45.2%) and 53 (67%) in groups 1 and 2, respectively (P = 0.8). High-grade complications (?3) included 3 (3.5%) and 12 (15.1%) in groups 1 and 2, respectively (P = 0.02). The blood transfusion rate was 24.5%, the perioperative mortality rate was 1.2% and the re-admission rate within the first 30 days after OP was 1.2%. High-grade complications were significantly associated with a greater resected prostate weight (odds ratio 1.08, 95% CI 1.001-1.17, P = 0.046). CONCLUSION: The OP procedure is associated with a significant perioperative morbidity that correlated significantly with the resected prostate weight, especially for high-grade complications. PMID- 26558108 TI - Reconstructive surgery for idealising penile shape and restoring erectile function in patients with penile dysmorphology and erectile dysfunction. AB - OBJECTIVE: To report an innovative combination of two surgical procedures to treat patients with erectile dysfunction and penile deviation, arising from advances in penile anatomy. PATIENTS AND METHODS: From October 1998 to October 2011, 132 men (aged 23-39 years) underwent penile venous stripping and corporoplasty. Of these, 37 were allocated to a transverse and 95 to a longitudinal group, with an infrapubic transverse or pubic median longitudinal approach, respectively. The abridged five-item version of the International Index of Erectile Function (IIEF-5) and cavernosography were used for assessment, as necessary. Under acupuncture-aided local anaesthesia, and after a circumferential incision, the deep dorsal vein and cavernous veins were completely stripped, with 6-0 Nylon sutures for ligation, followed by tunical surgery for correcting the penile shape. RESULTS: In the transverse and longitudinal groups the mean (SD) duration of surgery was 4.6 (0.2) and 4.8 (0.3) h, respectively. Before surgery the mean (SD) IIEF-5 score was 9.4 (2.3) and 9.6 (2.1), which increased to 20.6 (2.4) and 20.8 (2.7), respectively, after surgery. The penile shape (<15 degrees ) was deemed satisfactory in 92% (34/37) and 96% (91/95) of patients in the transverse and longitudinal groups, respectively. The cavernosograms consistently showed a good penile shape. There were significant differences in the mean (SD) duration of penile oedema, at 3.2 (1.6) vs. 11.9 (2.1) days, the overall satisfaction rate and the prevalence of hypertrophied scarring (all P < 0.001). CONCLUSION: This combination of unique penile venous stripping with a pubic median longitudinal approach and an anatomy-based corporoplasty is ideally suited to the simultaneous restoration of penile erectile function and morphological reconstruction. PMID- 26558109 TI - The venous drainage of the corpora cavernosa in the human penis. AB - OBJECTIVE: To study the drainage proportions from the corpora cavernosa in defrosted human cadavers, as the veins related to penile erection were recently depicted to comprise the deep dorsal vein (DDV), a pair of cavernous veins (CVs) and two pairs of para-arterial veins (PAVs), as opposed to a single DDV between Buck's fascia and the tunica albuginea of the human penis. MATERIALS AND METHODS: With no formalin fixation, 10 defrosted male human cadavers were used for this study. After injecting a 10% solution of colloid, and with the intracavernous pressure (ICP) fixed at 90 mmHg, the perfusion rate was recorded before and after the DDV, CVs and PAVs were removed, respectively. Finally, measurements were again recorded after penile arterial ligation. Cavernosography was used if required. RESULTS: The mean (range) perfusion rate for maintaining the ICP at 90 mmHg was 30.2 (15.5-90.8) mL/min, whereas the arterial perfusion rate was 2.8 (0.3-3.9) mL/min. The mean (range) drainage proportion of the corpora cavernosa was 60.5 (50.3-69.7)%, 11.9 (5.8-22.9)% and 11.4 (5.2-15.0)% via the DDV, CVs and PAVs, respectively. The remaining drainage proportion was 15.6 (14.1-18.1)%. This study shows the separate drainage contributions of the DDV, CVs and PAVs to the corpora cavernosa of the human penis. CONCLUSION: We conclude that the venous drainage system of the corpora cavernosa is much more complex than the previous depictions of it, and the consequent focus on a single DDV. This also shows the independent role of each venous system. PMID- 26558110 TI - On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: A randomised placebo-controlled clinical trial. AB - OBJECTIVES: To compare the clinical efficacy of the on-demand use of four drugs in the management of patients with premature ejaculation (PE), as the off-label use of selective serotonin-reuptake inhibitors and topical penile anaesthetics is frequently indicated for the management of patients with PE, and tramadol HCl and sildenafil citrate were also tried for managing this disorder, but with recommendations based on weak evidence. PATIENTS AND METHODS: This was a single centre, single-blind, placebo-controlled clinical trial conducted on 150 patients who had PE for >1 year. Patients were randomised equally into five groups. On demand tramadol, sildenafil, paroxetine, local lidocaine gel or placebo was given for patients in groups 1-5, respectively. During the month before treatment, the intravaginal ejaculation latency time (IELT) and sexual satisfaction scores (on a 0-5-point scale) were measured and compared to the mean IELT and sexual satisfaction scores recorded during 4 weeks of on-demand drug administration, with monitoring of any possible side-effects. RESULTS: Tramadol-treated patients had a significantly longer mean (SD) IELT, of 351 (119) s, than the other groups. Local anaesthetic was significantly better than paroxetine in prolonging the IELT, at 278 (111) vs. 186 (65) s, respectively. The improvement in sexual satisfaction was significantly better in the sildenafil group, with a mean (SD) improvement of 2.9 (1) points, than in the paroxetine and local anaesthetic groups, at 2.2 (0.9) and 1.9 (0.9) points, respectively. CONCLUSIONS: The four drugs significantly improved IELT values over placebo. Tramadol was associated with significantly longer IELT values, whilst sildenafil induced significantly better sexual satisfaction than the other drugs. The four drugs had tolerable side-effects. PMID- 26558111 TI - The efficacy of tamsulosin therapy after extracorporeal shock-wave lithotripsy for ureteric calculi: A prospective randomised, controlled study. AB - OBJECTIVE: To evaluate whether tamsulosin hydrochloride is effective as an adjunctive medical therapy to increase the effectiveness of extracorporeal shock wave lithotripsy (ESWL) for treating ureteric stones, and minimises the use of analgesic drugs after the procedure. PATIENTS AND METHODS: To treat single ureteric stones of 5-15 mm in diameter, 130 patients were treated with ESWL. After treatment, equal numbers of patients were randomly assigned to receive either the standard medical therapy alone (controls) or combined with 0.4 mg tamsulosin daily for ?12 weeks. All patients were followed up for 3 months or until an alternative treatment was offered. RESULTS: At 3 months the treatment was considered to be clinically successful in 55/65 (85%) of those receiving tamsulosin and in 58/65 (89%) of the controls (P = 0.34). When patients were classified according to stone size the success rate was similar in both groups (P = 0.22) for those with a stone of >10 mm. However, ureteric colic was reported in 12% of patients treated with standard therapy but in only 5% of those treated with tamsulosin (P = 0.006). The mean cumulative diclofenac dose was 380 mg/patient in the tamsulosin group and 750 mg/patient in the control group (P = 0.004). CONCLUSIONS: This study showed the effectiveness of tamsulosin as an adjunctive medical therapy after ESWL for ureteric stones, but it did not improve stone clearance when treating ureteric stones. However, it decreased the use of analgesics and reduced the complication rate, especially for steinstrasse. PMID- 26558112 TI - The efficacy of tamsulosin vs. nifedipine for the medical expulsive therapy of distal ureteric stones: A randomised clinical trial. AB - OBJECTIVES: To assess and compare, in a randomised clinical trial, the efficacy of tamsulosin and nifedipine as medical expulsive therapy for distal ureterolithiasis. PATIENTS AND METHODS: In all, 128 symptomatic patients with stones in the juxtavesical tract of the ureter were randomly divided into group 1 (64 patients) receiving oral nifedipine sustained-release 30 mg/day, and group 2 (64 patients) receiving tamsulosin 0.4 mg/day. Both groups received oral prednisolone 30 mg/day for 10 days and diclofenac 75 mg intramuscularly on demand. Patients were assessed by weekly ultrasonography with or with no abdominal computed tomography, during a follow-up of 4 weeks. The stone passage rate and time, analgesic use, hospitalisation and endoscopic interventions were evaluated. The results were analysed statistically using appropriate tests. RESULTS: The stone expulsion rate was 55% for group 1 and 80% for group 2 (P = 0.004). The mean stone size was 8.59 and 8.85 mm in groups 1 and 2, respectively. The mean expulsion time was 23 days for group 1 and 9 days for group 2 (P < 0.001). The mean number of diclofenac injections was 1.19 for group 1 and 0.42 for group 2 (P < 0.001). Eleven patients in group 1 vs. two in group 2 were hospitalised (P = 0.001). Twenty-six patients in group 1 and 13 in group 2 underwent ureteroscopy (P < 0.001). CONCLUSIONS: Medical expulsive therapy with tamsulosin should be considered as a first-line treatment for index cases of distal ureterolithiasis with no complications. The use of tamsulosin provides better stone expulsion than does nifedipine. PMID- 26558113 TI - The long-term results of laparoscopic retroperitoneal pyeloplasty in adults. AB - OBJECTIVES: To report the long-term outcome of laparoscopic retroperitoneal pyeloplasty (LRP) in adults. PATIENTS AND METHODS: Thirty patients underwent LRP for primary pelvi-ureteric junction obstruction (PUJO). Anderson-Hynes dismembered pyeloplasty was used in 28 patients and a Foley Y-V pyeloplasty in two. A JJ stent was inserted antegradely during the procedure. Patients were reviewed at 1 month after LRP for stent removal, and then at 6 and 12 months routinely, using excretory urography. RESULTS: The mean patient age was 29.7 years, with a female predominance of 60%. Conversion to open surgery was mandated by dense adhesions secondary to previous pyelonephritis in three patients, and difficulty in suturing in one. The mean (range) operative duration was 228 (190 280) min. There was a crossing vessel in 11 patients and it was not transposed in any. The mean hospital stay after LRP was 4.2 days. The mean (range) follow-up was 60 (29-106) months. Of the 26 patients who had complete laparoscopic procedures, 23 had no evidence of obstruction on long-term postoperative intravenous urography and/or diuretic renography. CONCLUSION: LRP combines the high functional success rate of open pyeloplasty in the long term and the minimally invasive morbidity of laparoscopy. PMID- 26558114 TI - The use of small intestinal submucosa graft for hypospadias repair: Pilot study. AB - OBJECTIVE: To evaluate the outcome of using commercially available (SIS) grafts for repairing hypospadias. Collagen-based acellular matrices, including SIS and bladder submucosa matrix, have been used to repair urethral strictures, with varying success, and patients with hypospadias and with inadequate or no genital skin need a substitute tissue for urethroplasty. PATIENTS AND METHODS: This pilot study included 12 patients (mean age 8 years, range 1.5-15) with hypospadias (distal in six, mid-shaft in four and proximal in two). They underwent a repair with four layers of prefabricated SIS as an onlay graft. The outcome was assessed for cosmetic appearance, urinary stream and the postvoid residual volume. The chi squared and Mann-Whitney U-tests were used to assess the relationship between preoperative factors and the outcome of the repair with SIS grafting. RESULTS: The mean (range) follow-up was 23 (6-36) months. Nine patients ultimately voided normally, with a good cosmetic appearance and no postvoid residual urine. Six patients had a successful repair with no further intervention, whilst three had small fistulae that were treated by simple closure. In three patients the graft failed, by complete disruption or stricture. Graft infection adversely affected the outcome of SIS grafting. CONCLUSIONS: The prefabricated SIS graft can be used as an alternative substitute for urethral reconstruction when genital skin is insufficient or lacking, as in circumcised patients or a repeat hypospadias repair. Graft infection is the chief reason for graft failure and should be prevented. Further studies with more patients are needed to confirm these preliminary results. PMID- 26558115 TI - Corrigendum to "Acute Amiodarone Pulmonary Toxicity after Drug Holiday: A Case Report and Review of the Literature". AB - [This corrects the article DOI: 10.1155/2015/927438.]. PMID- 26558116 TI - Nonclassical Congenital Adrenal Hyperplasia and Pregnancy. AB - Objective. The most common form of congenital adrenal hyperplasia (CAH) is 21 hydroxylase (21-OH) deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH) are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH) if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH. PMID- 26558117 TI - Successful Treatment of Leukemic Mature B-Cell Lymphoid Neoplasm with Similar Features to Splenic Marginal Zone Lymphoma Possessing Aberrant Myeloid Markers. AB - In splenic marginal zone lymphoma (SMZL), there are cases that cannot accurately be classified as such because of overlapping morphologic and/or immunophenotypic features. We report here a 76-year-old Japanese female, who showed leukemic B cell lymphoproliferative disease possessing characteristic features identified for SMZL. The patient was leukemic with white blood cell counts 49,400/uL (abnormal cells, 78.5%) and neoplastic cells were characterized by aberrant expression of myeloid markers with CD19(+)CD13(+) (64.2%) and CD20(+)CD11c(+) (25.1%). Considering her history of previous chemotherapy and systemic leukemic phase of the disease, we treated the patient without performing splenectomy, with successful use of a combination of rituximab/bendamustine hydrochloride and of rituximab/cladribine. The patient has been in a complete remission longer than 44 months, with no detectable M-protein. PMID- 26558118 TI - Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency. AB - A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine. PMID- 26558119 TI - Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B. AB - Central nervous system (CNS) infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL) who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI) showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration. PMID- 26558120 TI - Pauci-Immune Necrotizing and Crescentic Glomerulonephritis with Membranous Lupus Nephritis, Fifteen Years after Initial Diagnosis of Secondary Membranous Nephropathy. AB - Renal involvement in systemic lupus erythematosus (SLE) is usually immune complex mediated and may have multiple different presentations. Pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) refers to extensive glomerular inflammation with few or no immune deposits that may result in rapid decline in renal function. We report a case of a 79-year-old Hispanic male with a history of secondary membranous nephropathy (diagnosed by renal biopsy 15 years previously) who was admitted with acute kidney injury and active urinary sediment. P-ANCA titers and anti-myeloperoxidase antibodies were positive. The renal biopsy was diagnostic for NCGN superimposed on a secondary membranous nephropathy. A previous diagnosis of SLE based on American College of Rheumatology criteria was discovered via Veteran's Administration records review after the completion of treatment for pauci-immune NCGN. ANCAs are detected in 20-31% of patients with SLE. There may be an association between SLE and ANCA seropositivity. In patients with lupus nephritis and biopsy findings of necrotizing and crescentic glomerulonephritis, without significant immune complex deposition, ANCA testing should be performed. In patients with secondary membranous nephropathy SLE should be excluded. PMID- 26558121 TI - Prenatal Diagnosis of Cardiac Diverticulum with Pericardial Effusion in the First Trimester of Pregnancy with Resolution after Early Pericardiocentesis. AB - Cardiac diverticulum is a rare anomaly, which may present in association with pericardial effusion. Only few cases diagnosed during fetal life have been published and only in 12 cases pericardiocentesis was made with good postnatal outcomes in 83% of the cases. In the first trimester of pregnancy only 6 cases were reported. We described the largest series of cases published. We describe a case of cardiac diverticulum complicated with pericardial effusion during the first trimester of pregnancy and resolved by intrauterine pericardiocentesis at 17 weeks of pregnancy. We made a systematic review of the literature with the cases reported of cardiac diverticulum, management, and outcomes. PMID- 26558122 TI - Abdominal Sarcoidosis May Mimic Peritoneal Carcinomatosis. AB - Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It shows a great variety of clinical presentation, organ involvement, and disease progression. Lungs and lymphoid system are the most common sites involved with a frequency of 90% and 30%, respectively. Extrapulmonary involvement of sarcoidosis is reported in 30% of patients and abdomen is the most frequent site. Furthermore, peritoneal involvement is extremely rare in sarcoidosis. The case presented here described peritoneal manifestations of sarcoidosis without involvement of lungs. A 78-year-old woman possessing signs of malignancy on blood test and abdominal magnetic resonance imaging underwent laparatomy with a suspicion of ovarian malignancy. The macroscopic interpretation during surgery was peritoneal carcinomatosis. Total abdominal hysterectomy, bilateral salpingo oophorectomy, peritoneal biopsies, total omentectomy, and appendectomy were performed. Final histopathological result revealed the diagnosis of sarcoidosis. Clinicians must keep in mind that peritoneal sarcoidosis can mimic intra abdominal malignancies. PMID- 26558123 TI - Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome. AB - Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID- 26558125 TI - Secondary Radial Nerve Palsy after Minimally Invasive Plate Osteosynthesis of a Distal Humeral Shaft Fracture. AB - Minimally invasive plate osteosynthesis is a widely used procedure for the treatment of fractures of the femur and the tibia. For a short time it is also used for the treatment of humeral shaft fractures. Among other advantages, the ambassadors of this technique emphasize the lower risk of nerve injuries when compared to open reduction and internal fixation. We report the case of secondary radial nerve palsy caused by percutaneous fixation of a plate above the antecubital fold. The nerve did not recover and the patient needed a tendon transfer to regain active extension of the fingers. This case points to the importance of adequate exposure of the bone and plate if a humeral shaft fracture extends far distally. PMID- 26558124 TI - Migrating Polyarthritis as a Feature of Occult Malignancy: 2 Case Reports and a Review of the Literature. AB - Malignant disease may be associated with a wide variety of musculoskeletal syndromes. Rarely the musculoskeletal system can be indirectly affected by paraneoplastic phenomena, such as carcinomatous polyarthritis (CP). The differential diagnosis for CP is broad and is often a diagnosis of exclusion. CP often presents similarly to other forms of inflammatory arthritis, and a detailed history and physical examination can often distinguish CP from other more common causes of polyarticular arthritis. However serological tests such as rheumatoid factor (RF) and anti-citrullinated peptide (anti-CCP) antibody positivity, while rare, can be misleading. Clinical awareness and suspicion are paramount in achieving an accurate diagnosis and early detection of an occult neoplasm is critical for prompt management and therapy. We report two cases presenting with this unique clinical phenotype associated with paraneoplastic polyarthropathy and review the literature. PMID- 26558126 TI - A Rare Differential Diagnosis of a Nasal Tumor: Case Report and Literature Review. AB - Vascular leiomyomas or angioleiomyomas are rare tumors that can be found in the nasal cavity. The etiology of angioleiomyoma remains poorly understood and there are several hypotheses to explain the origin of sinonasal leiomyoma. We here describe the clinical and histological findings in a case study along with the feasibility of surgical treatment using a radiofrequency instrument. In particular, we describe the case of an adult patient with recurrent epistaxis because of a nasal angioleiomyoma and the performed treatment in the form of complete surgical excision. Radiological imaging is a helpful tool to give an indication of the extension of the tumor, as well as for the proper planning of the surgical approach. Either MRI or CT scans are found to be best suited for this purpose. This case report recommends the complete surgical excision of the angioleiomyoma, by either an endoscopic or an open procedure. This can be safely performed using a radiofrequency instrument as shown in this case with no recurrence during a follow-up of 12 months. PMID- 26558127 TI - Postdural Puncture Superior Sagittal Sinus Thrombosis in a Juvenile Case of Clinically Isolated Syndrome. AB - Background. The causes of cerebral venous thrombosis (CVT) are manifold as is its clinical presentation. Case. We report the case of a CVT following lumbar puncture and intravenous glucocorticosteroid therapy in a female adolescent with a clinically isolated syndrome and risk factors for thrombosis. Conclusion. In adolescent patients with acute inflammatory disease undergoing lumbar puncture followed by intravenous high-dose glucocorticosteroid therapy, one should be aware of the elevated risk for thrombosis. A persistent headache with change in the headache pattern and loss of a postural component might be a sign for CVT, requiring emergency imaging of the brain. PMID- 26558128 TI - Corrigendum to "Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress". AB - [This corrects the article DOI: 10.1155/2015/591783.]. PMID- 26558129 TI - Posttraumatic Intradiploic Leptomeningeal Cyst: A Rare Complication of Head Trauma. AB - Posttraumatic intradiploic leptomeningeal cyst is an exceedingly uncommon complication of skull fracture in childhood with only about twenty-one cases described in literature till now. We report 2 such cases of intradiploic leptomeningeal cyst of occipital bone in two 17- and 21-year-old males presenting with headache with history of occipital bone fracture in childhood and briefly discuss its pathogenesis and differential diagnosis. PMID- 26558130 TI - Ileocaecal Intussusception with a Lead Point: Unusual MDCT Findings of Active Crohn's Disease Involving the Appendix. AB - Adult intussusception is a rare entity accounting for 1% of all bowel obstructions. Unlike intussusceptions in children, which are idiopathic in 90% of cases, adult intussusceptions have an identifiable cause (lead point) in the majority of cases. Crohn's disease (CD) may affect any part of the gastrointestinal tract, including the appendix. It was shown to be a predisposing factor for intussusception. Here, we report a rare case of adult intussusception with a lead point, emphasizing diagnostic input of multidetector computed tomography (MDCT) in a patient with active CD that involves the appendix. PMID- 26558131 TI - Insulinoma-Induced Hypoglycemia in a Patient with Insulinoma after Gastrojejunostomy for Prepyloric Ulcer. AB - Hyperinsulinism due to dumping syndrome following gastric surgery is an uncommon condition. It is specified with hypoglycemic attacks. However, linking symptoms to dumping syndrome in each patient to whom gastric surgery was performed leads to inappropriate diagnosis and therapy. Insulinoma and other causes that give rise to hyperinsulinemia should not be ignored and these diagnoses should be excluded. In this paper, 71-year-old male patient who was followed up for 2 years with a false conclusion of dumping syndrome and operated on due to insulinoma diagnosed at endoscopic ultrasonography is presented in the light of the literature. PMID- 26558132 TI - Treatment with Aortic Stent Graft Placement for Stanford B-Type Aortic Dissection in a Patient with an Aberrant Right Subclavian Artery. AB - A 71-year-old man visited our hospital with the chief complaint of back pain and was diagnosed with acute aortic dissection (Debakey type III, Stanford type B). He was found to have a variant branching pattern in which the right subclavian artery was the fourth branch of the aorta. We performed conservative management for uncomplicated Stanford type B aortic dissection, and the patient was discharged. An ulcer-like projection (ULP) was discovered during outpatient follow-up. Complicated type B aortic dissection was suspected, and we performed thoracic endovascular aortic repair (TEVAR). The aim of operative treatment was ULP closure; thus we placed two stent grafts in the descending aorta from the distal portion of the right subclavian artery. The patient was released without complications on postoperative day 5. Deliberate sizing and examination of placement location were necessary when placing the stent graft, but operative techniques allowed the procedure to be safely completed. PMID- 26558133 TI - The Association between the PR Interval and Left Ventricular Measurements in the Multiethnic Study of Atherosclerosis. AB - Introduction. Few studies have examined the association between the PR interval (PRi) and subclinical cardiovascular disease measures. Methods and Results. The Multiethnic Study of Atherosclerosis (MESA) is a population-based study of 6814 men and women aged 45-84 years without clinical cardiovascular disease and 4962 had complete baseline data on cardiac magnetic resonance imaging measures of LV dimension and ejection fraction and surface electrocardiogram. Linear regression models were constructed to determine the adjusted association between the PRi and measures of LV stroke volume, LV mass, LV end-systolic and end-diastolic volumes, and ejection fraction. Overall, mean age was 61.5 years, and 47.6% were male and race/ethnicity was white in 39.1%, Chinese in 13.1%, African-American in 25.7%, and Hispanic in 22.2%. The PRi ranged from 88 to 308 ms with a median value of 162 ms. As a continuous variable, every standard deviation unit (25 ms) increment in PRi was associated with a 2.00 mL (95% CI 1.52, 2.48) higher stroke volume, a 3.08 g (95% CI 2.30, 3.86) higher LV mass, a 1.36 g/m(2) (95% CI 0.96, 1.76) higher LV mass index, and 1.31 mL (95% CI 0.88, 1.73) higher end-systolic and 3.31 mL (95% CI 2.58, 4.03) higher end-diastolic volumes after adjustment for all covariates. No significant association was noted between the PRi and LV ejection fraction. Conclusions. A prolonged PRi is associated with LV measures and may in part explain the link between a prolonged PRi and cardiovascular outcomes. PMID- 26558134 TI - Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease. AB - Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD. PMID- 26558135 TI - Antiamnesic Effects of a Hydroethanolic Extract of Crinum macowanii on Scopolamine-Induced Memory Impairment in Mice. AB - Crinum macowanii has been found to contain alkaloids that have activity against acetylcholinesterase enzyme in vitro. The present study was undertaken to investigate the in vivo ability of hydroethanolic crude extract of Crinum macowanii to ameliorate memory impairment induced by scopolamine. Thirty-six male Balb/c mice weighing around 25-35 g were employed in the present investigation. Y maze and novel object recognition apparatus served as the exteroceptive behavioural models, and scopolamine-induced amnesia served as the interoceptive behavioural model. C. macowanii (10, 20, and 40 mg/kg p.o.) was administered in single doses to the mice. Donepezil (3 mg/kg p.o.) was used as a positive control agent. C. macowanii extract reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task. C. macowanii 40 mg/kg showed significant activity (p < 0.05 versus negative control), comparable to that of the positive control. C. macowanii also showed memory-enhancing activity against scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by a dose-dependent increase in the discrimination index. The results indicate that the hydroethanolic extract of C. macowanii may be a useful memory restorative mediator in the treatment of cognitive disorders such as Alzheimer's disease. PMID- 26558136 TI - Evaluation of Podoplanin in Oral Leukoplakia and Oral Squamous Cell Carcinoma. AB - Background. Recent studies have demonstrated that podoplanin was expressed in some dysplastic lesions adjacent to primary oral cancers suggesting that podoplanin expression may occur in early oral tumorigenesis and lymphangiogenesis and therefore is related to tumor growth. The purpose of this study is to determine the role of podoplanin as a biomarker for cancer risk assessment in oral leukoplakia and correlation of podoplanin expression with grades of oral squamous cell carcinoma (OSCC). Materials and Methods. In the present retrospective study, podoplanin expression was investigated immunohistochemically in 40 patients each of oral leukoplakia and OSCC. The scores were analyzed statistically using one-way ANOVA test followed by Tukey HSD. Results. By applying one-way ANOVA test, there was a highly significant increase of the podoplanin expression from mild to severe dysplasia and from well to poorly differentiated OSCC (P < 0.01). Statistically highly significant difference was present between scores of mild to moderate dysplasia, moderate to severe dysplasia, well to poorly differentiated OSCC, and moderately to poorly differentiated OSCC (Tukey HSD test, P < 0.01). Conclusion. Podoplanin can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions and as a tumor progression biomarker for advanced grades of OSCC. PMID- 26558137 TI - Knowledge, transfer, and innovation in physical literacy curricula. AB - Literate individuals possess knowledge and skill and can apply these to perform tasks in novel settings. Knowledge is at the heart of physical literacy and provides the foundation for knowing what to do and how and when to perform. In this paper I argue that physical literacy includes not only knowledge for performance but also the ability to apply knowledge and use knowledge for innovation. Scholars since the 1930s have addressed the role of knowledge in physical literacy designing curricula centered on transmitting knowledge through a range of interdisciplinary approaches to physical education. This emphasis on physical literacy curricula continues today in the Science, PE, & Me! and The Science of Healthful Living interdisciplinary curricula. PMID- 26558138 TI - Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration. AB - The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling, and hence activation of the IL-6/gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co cultures. Taken together, these findings show the function of macrophages as co inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover. PMID- 26558139 TI - Dopaminergic effects on in vitro osteogenesis. AB - Multiple growth factors (e.g., BMP2, TGF-beta1, FGF2) and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine (PDA) and dopamine (DA) monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA's role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. mRNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1-D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression (ALP, BSP, OC, OSX, RUNX2, and Collagen1a2) with or without receptor antagonists (SCH233390 and GR103691). Two-way ANOVA was used for statistical analysis. All five DA receptors (D1, D2, D3, D4, and D5) mRNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days (P < 0.05). Osteogenic mineralization was significantly greater in the DA-treated group than control group (P < 0.05). Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair. PMID- 26558140 TI - Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9. AB - RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissue-specific Rbpjk mutant (Prx1Cre;Rbpjk(f/f) ), Rbpjk mutant/Sox9 haploinsufficient (Prx1Cre;Rbpjk(f/f);Sox9(f/+) ), and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors. PMID- 26558141 TI - Nanomaterials and bone regeneration. AB - The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID- 26558142 TI - Present state and future challenges in pediatric abdominal pain therapeutics research: Looking beyond the forest. AB - At the present time, it is nearly impossible to treat pediatric functional gastrointestinal disorders associated with pain in an evidence based fashion. This is due to the overall lack of controlled studies and, even more importantly, the complexity of the contributors to disease phenotype which are not controlled or accounted for in most therapeutic trials. In this manuscript, we review the challenges of defining entry criteria, controlling for the large number of biopsychosocial factors which may effect outcomes, and understanding pharmacokinetic and pharmacodynamic factors when designing therapeutic trials for abdominal pain in children. We also review the current state of pediatric abdominal pain therapeutics and discuss trial design considerations as we move forward. PMID- 26558143 TI - Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients. AB - The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naive kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients. PMID- 26558144 TI - Flatography: Detection of gastrointestinal diseases by faecal gas analysis. AB - Patients presenting with gastro-intestinal symptoms might suffer from a range of possible underlying diseases. An unmet need exists for novel cost-effective, reproducible, easy-to-perform and non-invasive tests. Hippocrates used body odours to diagnose diseases circa 460 before Christ. The art of diagnostic smelling is making a promising high-tech come-back with portable "electronic diagnostic noses". Analysis of faecal volatile organic compounds is a novel field in metabolomics with considerable potential to improve the diagnosis, phenotyping and monitoring of gastro-intestinal disease. Challenges will be to mature over the coming years by development of a standardized methodology for stool sample collection, storage, handling and analysis. Furthermore, key volatiles need to be identified to improve test accuracy and sensitivity by development of sensors tailored toward the accurate identification of disease specific volatiles. If these challenges are adequately faced, analysis of faecal volatiles has realistic potential to considerably improve screening, diagnosis and disease monitoring for gastro-intestinal diseases. PMID- 26558145 TI - Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis. AB - Recently, direct antiviral agents (DAAs) have been increasingly used for the treatment of chronic hepatitis C virus (HCV) infections, replacing interferon based regimens that have severe adverse effects and low tolerability. The constant supply of new DAAs makes shorter treatment periods with enhanced safety possible. The efficacy of DAAs for treatment of compensated liver cirrhosis (LC) is not less than that for treatment of non-cirrhotic conditions. These clinical advantages have been useful in pre- and post-liver transplantation (LT) settings. Moreover, DAAs can be used to treat decompensated HCV-induced LC in elderly patients or those with severe complications otherwise having poor prognosis. Although encouraging clinical data are beginning to appear, the actual efficacy of DAAs for suppressing disease progression, allowing delisting for LT and, most importantly, improving prognosis of patients with decompensated HCV-LC remains unknown. Case-control studies to examine the short- or long-term effects of DAAs for treatment of decompensated HCV-LC are urgently need. PMID- 26558146 TI - Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARalpha, PPARbeta/delta, and PPARgamma, have been identified so far. PPARalpha is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPARbeta/delta is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPARalpha or PPARgamma target genes. PPARgamma1 and gamma2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPARgamma1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPARalpha agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPARalpha agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPARgamma activators. In all the studies, both the PPARgamma activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARalpha and PPARgamma may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs alpha and gamma in gastric ulcer. PMID- 26558147 TI - Helicobacter pylori: Effect of coexisting diseases and update on treatment regimens. AB - The presence of concomitant diseases is an independent predictive factor for non Helicobacter pylori (H. pylori) peptic ulcers. Patients contracting concomitant diseases have an increased risk of developing ulcer disease through pathogenic mechanisms distinct from those of H. pylori infections. Factors other than H. pylori seem critical in peptic ulcer recurrence in end stage renal disease (ESRD) and cirrhotic patients. However, early H. pylori eradication is associated with a reduced risk of recurrent complicated peptic ulcers in patients with ESRD and liver cirrhosis. Resistances to triple therapy are currently detected using culture-based and molecular methods. Culture susceptibility testing before first- or second-line therapy is unadvisable. Using highly effective empiric first-line and rescue regimens can yield acceptable results. Sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance. Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective in patients with dual- (clarithromycin- and metronidazole-) resistant H. pylori strains. We aim to review the prevalence of and eradication therapy for H. pylori infection in patients with ESRD and cirrhosis. Moreover, we summarized the updated H. pylori eradication regimens. PMID- 26558148 TI - Mesalazine preparations for the treatment of ulcerative colitis: Are all created equal? AB - Oral mesalazine (also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate ulcerative colitis, with high rates of efficacy in induction and maintenance of remission. The therapeutic effect of mesalazine occurs topically at the site of diseased colonic mucosa. A myriad of oral mesalazine preparations have been formulated with various drug delivery methods to minimize systemic absorption and maximise drug availability at the inflamed colonic epithelium. It remains unclear whether different oral mesalazine formulations are bioequivalent. This review aims to evaluate the differences between mesalazine formulations based on the currently available literature and explore factors which may influence the selection of one agent above another. PMID- 26558149 TI - Pharmacotherapy for the management of achalasia: Current status, challenges and future directions. AB - This article reviews currently available pharmacological options available for the treatment of achalasia, with a special focus on the role of botulinum toxin (BT) injection due to its superior therapeutic effect and side effect profile. The discussion on BT includes the role of different BT serotypes, better pharmacological formulations, improved BT injection techniques, the use of sprouting inhibitors, designer recombinant BT formulations and alternative substances used in endoscopic injections. The large body of ongoing research into achalasia and BT may provide a stronger role for BT injection as a form of minimally invasive, cost effective and efficacious form of therapy for patients with achalasia. The article also explores current issues and future research avenues that may prove beneficial in improving the efficacy of pharmacological treatment approaches in patients with achalasia. PMID- 26558150 TI - Pregnancy and inflammatory bowel diseases: Current perspectives, risks and patient management. AB - Inflammatory bowel diseases (IBD) are chronic idiopathic inflammatory conditions characterized by relapsing and remitting episodes of inflammation which can affect several different regions of the gastrointestinal tract, but also shows extra-intestinal manifestations. IBD is most frequently diagnosed during peak female reproductive years, with 25% of women with IBD conceiving after their diagnosis. While IBD therapy has improved dramatically with enhanced surveillance and more abundant and powerful treatment options, IBD disease can have important effects on pregnancy and presents several challenges for maintaining optimal outcomes for mothers with IBD and the developing fetus/neonate. Women with IBD, the medical team treating them (both gastroenterologists and obstetricians/gynecologists) must often make highly complicated choices regarding conception, pregnancy, and post-natal care (particularly breastfeeding) related to their choice of treatment options at different phases of pregnancy as well as post-partum. This current review discusses current concerns and recommendations for pregnancy during IBD and is intended for gastroenterologists, general practitioners and IBD patients intending to become, (or already) pregnant, and their families. We have addressed patterns of IBD inheritance, effects of IBD on fertility and conception (in both men and women), the effects of IBD disease activity on maintenance of pregnancy and outcomes, risks of diagnostic procedures during pregnancy and potential risks and complications associated with different classes of IBD therapeutics. We also have evaluated the clinical experience using "top-down" care with biologics, which is currently the standard care at our institution. Post-partum care and breastfeeding recommendations are also addressed. PMID- 26558151 TI - Diagnosis and therapy of non-variceal upper gastrointestinal bleeding. AB - Non-variceal upper gastrointestinal bleeding (UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions, erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor (PPI) therapy. These drugs are highly effective but the best route of application (oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal anti-inflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased. PMID- 26558153 TI - Autoimmune pancreatitis and cholangitis. AB - Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings. PMID- 26558154 TI - Age-related differences in celiac disease: Specific characteristics of adult presentation. AB - Celiac disease may appear both in early childhood and in elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients. PMID- 26558152 TI - Antibiotic treatment for Helicobacter pylori: Is the end coming? AB - Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID- 26558155 TI - Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis. AB - AIM: To evaluate the effect of orally administered plecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models. METHODS: The cyclic guanosine monophosphate (cGMP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cell-based assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid (5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium (DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic (TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout (TCRalpha(-/-)) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity. RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C (GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cGMP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs (0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity (P < 0.05) and disease activity index (P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRalpha(-/-) mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. PMID- 26558157 TI - Typical and atypical symptoms of gastro esophageal reflux disease: Does Helicobacter pylori infection matter? AB - AIM: To analyze whether the presence of Helicobacter pylori (H. pylori) infection could affect the quality of symptoms in gastro-esophageal reflux disease (GERD) patients. METHODS: one hundred and forty-four consecutive patients referred to our Unit for suspected GERD were recruited for the study. All patients underwent esophageal pH-metric recording. For those with a positive test, C13 urea breath test was then performed to assess the H. pylori status. GERD patients were stratified according to the quality of their symptoms and classified as typical, if affected by heartburn and regurgitation, and atypical if complaining of chest pain, respiratory and ears, nose, and throat features. H. pylori-negative patients were also asked whether they had a previous diagnosis of H. pylori infection. If a positive response was given, on the basis of the time period after successful eradication, patients were considered as "eradicated" (E) if H. pylori eradication occurred more than six months earlier or "recently eradicated" if the therapy had been administered within the last six months. Patients without history of infection were identified as "negative" (N). chi (2) test was performed by combining the clinical aspects with the H. pylori status. RESULTS: one hundred and twenty-nine of the 144 patients, including 44 H. pylori-positive and 85 H. pylori-negative (41 negative, 21 recently eradicated, 23 eradicated more than 6 mo before), were eligible for the analysis. No difference has been found between H. pylori status and either the number of reflux episodes (138 +/- 23 vs 146 +/- 36, respectively, P = 0.2, not significant) or the percentage of time with pH values < 4 (6.8 +/- 1.2 vs 7.4 +/- 2.1, respectively, P = 0.3, not significant). The distribution of symptoms was as follows: 13 typical (30%) and 31 atypical (70%) among the 44 H. pylori-positive cases; 44 typical (52%) and 41 atypical (48%) among the 85 H. pylori-negative cases, (P = 0.017 vs H. pylori+; OR = 2.55, 95%CI: 1.17-5.55). Furthermore, clinical signs in patients with recent H. pylori eradication were similar to those of H. pylori-positive (P = 0.49; OR = 1.46, 95%CI: 0.49-4.37); on the other hand, patients with ancient H. pylori eradication showed a clinical behavior similar to that of H. pylori-negative subjects (P = 0.13; OR = 0.89, 95%CI: 0.77-6.51) but different as compared to the H. pylori-positive group (P < 0.05; OR = 3.71, 95%CI: 0.83-16.47). CONCLUSION: Atypical symptoms of GERD occur more frequently in H. pylori-positive patients than in H. pylori-negative subjects. In addition, atypical symptoms tend to decrease after H. pylori eradication. PMID- 26558158 TI - Prevalence of eosinophilic oesophagitis in adults presenting with oesophageal food bolus obstruction. AB - AIM: To look at the relationship between eosinophilic oesophagitis (EO) and food bolus impaction in adults. METHODS: We retrospectively analysed medical records of 100 consecutive patients who presented to our hospital with oesophageal food bolus obstruction (FBO) between 2012 and 2014. In this cohort, 96 were adults (64% male), and 4 paediatric patients were excluded from the analysis as our centre did not have paediatric gastroenterologists. Eighty-five adult patients underwent emergency gastroscopy. The food bolus was either advanced into the stomach using the push technique or retrieved using a standard retrieval net. Biopsies were obtained in 51 patients from the proximal and distal parts of the oesophagus at initial gastroscopy. All biopsy specimens were assessed and reviewed by dedicated gastrointestinal pathologists at the Department of Pathology, University Hospital Geelong. The diagnosis of EO was defined and established by the presence of the following histological features: (1) peak eosinophil counts > 20/hpf; (2) eosinophil microabscess; (3) superficial layering of eosinophils; (4) extracellular eosinophil granules; (5) basal cell hyperplasia; (6) dilated intercellular spaces; and (7) subepithelial or lamina propria fibrosis. The histology results of the biopsy specimens were accessed from the pathology database of the hospital and recorded for analysis. RESULTS: Our cohort had a median age of 60. Seventeen/51 (33%) patients had evidence of EO on biopsy findings. The majority of patients with EO were male (71%). Classical endoscopic features of oesophageal rings, furrows or white plaques and exudates were found in 59% of patients with EO. Previous episodes of FBO were present in 12/17 patients and 41% had a history of eczema, hay fever or asthma. Reflux oesophagitis and benign strictures were found in 20/34 patients who did not have biopsies. CONCLUSION: EO is present in approximately one third of patients who are admitted with FBO. Biopsies should be performed routinely at index endoscopy in order to pursue this treatable cause of long term morbidity. PMID- 26558156 TI - Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a(-/-) mice. AB - AIM: To investigate the ability of a Prunella vulgaris (P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a(-/-) mice. METHODS: Vehicle (5% ethanol) or P. vulgaris ethanolic extract (2.4 mg/d) were administered daily by oral gavage to mdr1a(-/-) or wild type FVB(WT) mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencing weight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a(-/-) mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle treated mdr1a(-/-) mice. Oral administration of the P. vulgaris extract resulted in reduced (P < 0.05) serum levels of IL-10 (4.6 +/- 2 vs 19.4 +/- 4), CXCL9 (1319.0 +/- 277 vs 3901.0 +/- 858), and TNFalpha (9.9 +/- 3 vs 14.8 +/- 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1alpha, Mmp10, VCAM-1, ICAM, IL-2, and TNFalpha in the colonic mucosa of mdr1a(-/-) mice compared to vehicle-treated mdr1a(-/-) mice. Histologically, several microscopic parameters were reduced (P < 0.05) in P. vulgaris-treated mdr1a(-/-) mice, as was myeloperoxidase activity in the colon (2.49 +/- 0.16 vs 3.36 +/- 0.06, P < 0.05). The numbers of CD4(+) T cells (2031.9 +/- 412.1 vs 5054.5 +/- 809.5) and germinal center B cells (2749.6 +/- 473.7 vs 4934.0 +/- 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a(-/-) were significantly reduced (P < 0.05) from vehicle-treated mdr1a(-/-) mice. Vehicle treated mdr1a(-/-) mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a(-/-) mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a(-/-) mice. PMID- 26558159 TI - Massive duodenal variceal bleed; complication of extra hepatic portal hypertension: Endoscopic management and literature review. AB - Bleeding from duodenal varices is reported to be a catastrophic and often fatal event. Most of the cases in the literature involve patients with underlying cirrhosis. However, approximately one quarter of duodenal variceal bleeds is caused by extrahepatic portal hypertension and they represent a unique population given their lack of liver dysfunction. The authors present a case where a 61-year old male with history of remote crush injury presented with bright red blood per rectum and was found to have bleeding from massive duodenal varices. Injection sclerotherapy with ethanolamine was performed and the patient experienced a favorable outcome with near resolution of his varices on endoscopic follow-up. The authors conclude that sclerotherapy is a reasonable first line therapy and review the literature surrounding the treatment of duodenal varices secondary to extrahepatic portal hypertension. PMID- 26558160 TI - Preoperative detection of intrahepatic venovenous shunt treated by microwave precoagulation during right hepatectomy. AB - A 53-year-old woman underwent a 2-stage right hepatectomy for bilobar metastasis of an ileal neuroendocrine carcinoma. Preoperative three-dimensional computed tomography reconstruction helped to diagnose an intrahepatic venovenous shunts from the right and middle hepatic veins to the left hepatic vein, which could cause a intraoperative bleeding. Hemostasis was performed by means of precoagulation with microwave-assisted coagulation. PMID- 26558161 TI - Predicting Prognosis of Early-Stage Non-Small Cell Lung Cancer Using the GeneFx(r) Lung Signature. AB - Use of adjuvant chemotherapy remains a complex decision in the treatment of early stage non-small cell lung cancer (NSCLC), with risk of recurrence being the primary indicator (i.e. adjuvant chemotherapy is considered for patients at high risk of recurrence but may not be beneficial for patients at low risk). However, although several clinical and pathological factors are typically considered when assessing the risk of recurrence, none are significantly associated with clinical outcome with the exception of tumor size. GeneFx(r) Lung (HelomicsTM Corporation, Pittsburgh, PA) is a multi-gene RNA expression signature that classifies early stage NSCLC patients as high-risk or low-risk for disease recurrence. GeneFx Lung risk category has been shown to be significantly associated with overall survival in several independent clinical studies. The published literature regarding the analytical validity, clinical validity and clinical utility of GeneFx Lung is summarized herein. PMID- 26558162 TI - An improved hybrid multi-criteria/multidimensional model for strategic industrial location selection: Casablanca industrial zones as a case study. AB - In this paper, we examine the issue of strategic industrial location selection in uncertain decision making environments for implanting new industrial corporation. In fact, the industrial location issue is typically considered as a crucial factor in business research field which is related to many calculations about natural resources, distributors, suppliers, customers, and most other things. Based on the integration of environmental, economic and social decisive elements of sustainable development, this paper presents a hybrid decision making model combining fuzzy multi-criteria analysis with analytical capabilities that OLAP systems can provide for successful and optimal industrial location selection. The proposed model mainly consists in three stages. In the first stage, a decision making committee has been established to identify the evaluation criteria impacting the location selection process. In the second stage, we develop fuzzy AHP software based on the extent analysis method to assign the importance weights to the selected criteria, which allows us to model the linguistic vagueness, ambiguity, and incomplete knowledge. In the last stage, OLAP analysis integrated with multi-criteria analysis employs these weighted criteria as inputs to evaluate, rank and select the strategic industrial location for implanting new business corporation in the region of Casablanca, Morocco. Finally, a sensitivity analysis is performed to evaluate the impact of criteria weights and the preferences given by decision makers on the final rankings of strategic industrial locations. PMID- 26558163 TI - A chemical energy approach of avascular tumor growth: multiscale modeling and qualitative results. AB - In the present manuscript we propose a lattice free multiscale model for avascular tumor growth that takes into account the biochemical environment, mitosis, necrosis, cellular signaling and cellular mechanics. This model extends analogous approaches by assuming a function that incorporates the biochemical energy level of the tumor cells and a mechanism that simulates the behavior of cancer stem cells. Numerical simulations of the model are used to investigate the morphology of the tumor at the avascular phase. The obtained results show similar characteristics with those observed in clinical data in the case of the Ductal Carcinoma In Situ (DCIS) of the breast. PMID- 26558164 TI - Diversity of culturable bacterial endophytes of saffron in Kashmir, India. AB - Saffron (Crocus sativus) is a medicinally important plant. The Kashmir valley (J&K, India) emblematizes one of the major and quality saffron producing areas in the world. Nonetheless, the area has been experiencing a declining trend in the production of saffron during the last decade. Poor disease management is one of the major reasons for declining saffron production in the area. Endophytes are known to offer control against many diseases of host plant. During the present study, culturable bacterial endophytes were isolated from saffron plant, identified and assessed for plant growth promoting activities. Molecular and phylogenetic analysis grouped the fifty-four bacterial isolates into eleven different taxa, viz. Bacillus licheniformis, B. subtilis, B. cereus, B. humi, B. pumilus, Paenibacillus elgii, B. safensis, Brevibacillus sp., Pseudomonas putida, Staphylococcus hominis and Enterobacter cloacae. The results were also supported with the identification based on BIOLOG system. B. licheniformis was the dominant endophyte in both leaves and corms of saffron. 81 % isolates showed lipase activity, 57 % cellulase, 48 % protease, 38 % amylase, 33 % chitinase and 29 % showed pectinase activity. 24 % of the isolates were phosphate solublizers, 86 % showed siderophore production and 80 % phytohormone production potential. The present repository of well characterized bacterial endophytes of saffron, have plant growth promoting potential which can be explored further for their respective roles in the biology of the saffron plant. PMID- 26558165 TI - Bilateral corticosteroid-induced osteonecrosis of the femoral head detected at a 6-week interval. AB - INTRODUCTION: Corticosteroid-induced osteonecrosis of the femoral head (ONFH) often affects both femoral heads. Such bilateral ONFH cases are generally detected concurrently on magnetic resonance imaging (MRI). On the other hand, in unilateral cases, it is rare that contralateral ONFH is subsequently detected. We herein report a case in which bilateral ONFH was detected in both femoral heads by repeated MRI examination at an interval of 6 weeks. CASE DESCRIPTION: A 34 year-old man with purpura nephritis was started on corticosteroid therapy with prednisolone at 30 mg/day. Eight months after the initiation of corticosteroid therapy, he complained of left hip pain with no antecedent triggering activity. MRI obtained 8.5 months after the initiation of corticosteroid therapy showed the findings of osteonecrosis of the left femoral head, while no abnormalities were detected in the right femoral head. On the second MRI obtained 10 months after the initiation of corticosteroid treatment, however, osteonecrosis of the right femoral head was newly detected without an increase of the corticosteroid dose. CONCLUSIONS: This case may indicate that corticosteroid-induced bilateral ONFH do not always develop at the same time. PMID- 26558166 TI - Review of the tactical evaluation tools for youth players, assessing the tactics in team sports: football. AB - For sports assessment to be comprehensive, it must address all variables of sports development, such as psychological, social-emotional, physical and physiological, technical and tactical. Tactical assessment has been a neglected variable until the 1980s or 1990s. In the last two decades (1995-2015), the evolution of tactical assessment has grown considerably, given its importance in game performance. The aim of this paper is to compile and analyze different tactical measuring tools in team sports, particularly in soccer, through a bibliographical review. Six tools have been selected on five different criteria: (1) Instruments which assess tactics, (2) The studies have an evolution approach related to the tactical principles, (3) With a valid and reliable method, (4) The existence of publications mentioning the tool in the method, v. Applicable in different sports contexts. All six tools are structured around seven headings: introduction, objective(s), tactical principles, materials, procedures, instructions/rules of the game and published studies. In conclusion, the teaching learning processes more tactical oriented have useful tactical assessment instrument in the literature. The selection of one or another depends some context information, like age and level of expertise of the players. PMID- 26558167 TI - Erratum to: Comparison of the trifecta outcomes of robotic and open nephron sparing surgeries performed in the robotic era of a single institution. AB - [This corrects the article DOI: 10.1186/s40064-015-1274-2.]. PMID- 26558169 TI - Improved Bat algorithm for the detection of myocardial infarction. AB - The medical practitioners study the electrical activity of the human heart in order to detect heart diseases from the electrocardiogram (ECG) of the heart patients. A myocardial infarction (MI) or heart attack is a heart disease, that occurs when there is a block (blood clot) in the pathway of one or more coronary blood vessels (arteries) that supply blood to the heart muscle. The abnormalities in the heart can be identified by the changes in the ECG signal. The first step in the detection of MI is Preprocessing of ECGs which removes noise by using filters. Feature extraction is the next key process in detecting the changes in the ECG signals. This paper presents a method for extracting key features from each cardiac beat using Improved Bat algorithm. Using this algorithm best features are extracted, then these best (reduced) features are applied to the input of the neural network classifier. It has been observed that the performance of the classifier is improved with the help of the optimized features. PMID- 26558168 TI - Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow. AB - INTRODUCTION: HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. CASE DESCRIPTION: A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 ug/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. DISCUSSION AND EVALUATION: It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. CONCLUSIONS: The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue. PMID- 26558170 TI - Improving the optimized shea butter quality: a great potential of utilization for common consumers and industrials. AB - Industrials interest in fats as raw material, resides in their exceptional quality and potentialities of exploitation in several fields. This study aimed to exalt the optimized shea butter quality and present its wide potentialities of utilization. Hence, the characteristics of beige and yellow optimized shea butters were determined. Both samples recorded very weak acid (0.280 +/- 0.001 and 0.140 +/- 0.001 mgKOH/g) and peroxide (0.960 +/- 0.001 and 1.010 +/- 0.001 mEgO2/kg) indexes, when the iodine indexes (52.64 +/- 0.20 and 53.06 +/- 0.20 gI2/100 g) and the unsaponifiable matters (17.61 +/- 0.01 and 17.27 +/- 0.01 %) were considerable. The refractive indexes (1.454 +/- 0.00 and 1.453 +/- 0.00) and the pH (6.50 +/- 0.30 and 6.78 +/- 0.30) were statistically similar; but the specific gravity (0.915 +/- 0.01-0.79 +/- 0.01 and 0.94 +/- 0.01-0.83 +/- 0.01) and the viscosity (90.41 +/- 0.20-20.02 +/- 0.20 and 125.37 +/- 0.20-23.55 +/- 0.20 MPas) differed and decreased exponentially with the temperature increasing (35-65 degrees C), except for the specific gravity of the yellow butter which decreased linearly. The UV-Vis spectrum showed a high peak at 300 nm and a rapid decrease from 300 to 500 nm when the near infra-red one, revealed peaks at 450, 1200, 1400, 1725 and 2150 nm for all the samples. The chromatographic profile identified palmitic (16.42 and 26.36 %), stearic (32.39 and 36.36 %), oleic (38.12 and 29.09 %), linoleic (9.72 and 5.92 %) and arachidic (1.84 and 1.59 %) acids, and also exaltolide compound (1.51 and 0.68 %). The samples also contained essential minerals (Calcium, magnesium, zinc, iron, etc.) carotene (550 +/- 50 and 544 +/- 50 ppm), vitamins A (0.065 +/- 0.001 and 0.032 +/- 0.001 ug/g) and E (2992.09 +/- 1.90 and 3788.44 +/- 1.90 ppm) in relatively important amounts; neither microbiological germs nor heavy were detected. All these valorizing characteristics would confer to the optimized shea butters good aptitude for exportation and exploitation in food, cosmetic and pharmaceutical industries. PMID- 26558171 TI - The dipeptide conformations of all twenty amino acid types in the context of biosynthesis. AB - There have been many studies of dipeptide structure at a high level of accuracy using quantum chemical methods. Such calculations are resource-consuming (in terms of memory, CPU and other computational imperatives) which is the reason why most previous studies were restricted to the two simplest amino-acid residue types, glycine and alanine. We improve on this by extending the scope of residue types to include all 20 naturally occurring residue types. Our results reveal differences in secondary structure preferences for the all residue types. There are in most cases very deep energy troughs corresponding either to the polyproline II (collagen) helix and the alpha-helix or both. The beta-strand was not strongly favoured energetically although the extent of this depression in the energy surface is, while not "deeper" (energetically), has a wider extent than the other two types of secondary structure. There is currently great interest in the question of cotranslational folding, the extent to which the nascent polypeptide begins to fold prior to emerging from the ribosome exit tunnel. Accordingly, while most previous quantum studies of dipeptides were carried out in the (simulated) gas or aqueous phase, we wished to consider the first step in polypeptide biosynthesis on the ribosome where neither gas nor aqueous conditions apply. We used a dielectric constant that would be compatible with the water-poor macromolecular (ribosome) environment. PMID- 26558172 TI - A far-field radio-frequency experimental exposure system with unrestrained mice. AB - Many studies have been performed on exploring the effects of radio-frequency (RF) energy on biological function in vivo. In particular, gene expression results have been inconclusive due, in part, to a lack of a standardized experimental procedure. This research describes a new far field RF exposure system for unrestrained murine models that reduces experimental error. The experimental procedure includes the materials used, the creation of a patch antenna, the uncertainty analysis of the equipment, characterization of the test room, experimental equipment used and setup, power density and specific absorption rate experiment, and discussion. The result of this research is an experimental exposure system to be applied to future biological studies. PMID- 26558173 TI - Does amputation side influence sprint performances in athletes using running specific prostheses? AB - BACKGROUND: For athletes using running-specific prostheses (RSPs), current Paralympic guidelines for track events are generally based on level of amputation, not side of amputation. Although 200- and 400-m sprint races are performed in a counterclockwise direction, little is known about the effects of amputation side on race performance in athletes with unilateral lower limb amputation. The study aim was to test whether athletes using RSPs on their left side have slower race times than those using RSPs on their right side. FINDINGS: Athletes with unilateral lower limb amputation (N = 59 in total) participating in elite-level 200-m races were analyzed from publicly available Internet broadcasts. These races included the 2008 Beijing and 2012 London Paralympics, and the International Paralympic Committee Athletics World Championships in 2011 and 2013. For each athlete the official race time and amputation side were determined. There was no significant difference in number of participants and race time between left and right side amputees in T42 men, T44 men, and T44 women. CONCLUSION: The results of the present study suggest that sprint performance of athletes using RSPs is not affected by amputation side on a standard 400-m track. PMID- 26558174 TI - Use of botulinum toxin injections to treat peripheral stimulator induced facial muscle twitching: a case report. AB - BACKGROUND: Facial pain can be a management challenge. Peripheral nerve/field stimulation may be an effective option for refractory cases, but direct muscle stimulation with facial twitching may result. Botulinum toxin injections have been used for blepharospasm and may be effective when facial stimulation results in unacceptable facial muscle twitching due to peripheral stimulation. CASE PRESENTATION: A 53-year old female suffered with chronic, refractory facial pain and migraines. Her facial pain began after a root canal of a left upper molar. She was trialed and then permanently implanted with a 1 * 8 sub-compact percutaneous stimulator lead, resulting in improved pain control and reduced medication use. However, she experienced blepharospasm whenever the amplitude was above 2.75 A. Therefore, she was treated with botulinum toxin injections into her bilateral cheek, face, temple and occiput. This treatment provided excellent relief of the facial spasms, allowing her to use her stimulator at high amplitudes, and thereby maximizing her pain relief. She received two subsequent treatments of botulinum toxin injections at 5-month intervals with similar results. CONCLUSION: Peripheral nerve/field stimulation is being used for headaches and facial pain. An undesirable side effect of this emerging therapy is direct muscle stimulation. Botulinum toxin injections may be an effective treatment modality when stimulation techniques provide pain relief but also causes muscle twitching. PMID- 26558176 TI - Tribological properties of nanolamellar tungsten disulfide doped with zinc oxide nanoparticles. AB - Tribological properties of nanolamellar tungsten disulfide doped with zinc oxide nanoparticles were studied. Nanolamellar tungsten disulfide and ZnO nanoparticles produced by electrospark erosion of metal granules in an H2O2 solution were analyzed using the XRD, SEM and TEM techniques. According to the tribological measurements, ZnO nanoparticles did not significantly change the friction coefficient of nanolamellar WS2 at 25 degrees C in air, whereas they positively impact on wear resistance of nanolamellar WS2 at 400 degrees C. PMID- 26558175 TI - Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents. AB - In the present study, we have tried to establish the correlation between changes in Zeta potential with that of cell surface permeability using bacteria (Escherichia coli and Staphylococcus aureus). An effort has been made to establish Zeta potential as a possible marker for the assessment of membrane damage, with a scope for predicting alteration of cell viability. Cationic agents like, cetyl trimethyl ammonium bromide and polymyxin B were used for inducing alteration of Zeta potential, and the changes occurring in the membrane permeability were studied. In addition, assessment of poly-dispersity index (PDI), cell viability along with confocal microscopic analysis were performed. Based on our results, it can be suggested that alteration of Zeta potential may be correlated to the enhancement of membrane permeability and PDI, and it was observed that beyond a critical point, it leads to cell death (both Gram-positive and Gram-negative bacteria). The present findings can not only be used for studying membrane active molecules but also for understanding the surface potential versus permeability relationship. PMID- 26558177 TI - Patients' preferences and willingness-to-pay for postmenopausal hormone receptor positive, HER2-negative advanced breast cancer treatments after failure of standard treatments. AB - Patients' preferences increasingly play roles in cancer treatments. The objective of this study is to examine breast cancer patients' preferences and willingness to-pay (WTP) for postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer treatments after failure of standard treatments. Four attributes, i.e. progression free survival (PFS), anemia, pneumonitis, and cost, and their levels of exemestane and exemestane plus everolimus from literature and patient interviews were used to develop a discrete choice experiment questionnaire. Each questionnaire was composed of seven choice sets and each choice set contained those four attributes with different levels. Breast cancer patients were asked to choose one treatment alternative in each choice set. Multinomial logit model was used to determine relative preferences of each attribute and the WTP for all attributes and treatments were calculated. A total of 146 patients were included in study analyses. Results showed that the patients preferred treatments with higher PFS and lower side effects. The patients were willing to pay US$151.6, US$69.8, and US$278.3 per month in exchange for every 1 month increase in PFS and every 1 % decreased risk of anemia and pneumonitis, respectively. The patients were willing to pay for exemestane and exemestane plus everolimus US$551.8 and US$414.2 per month, respectively. In conclusion, patients weighted importance on PFS, anemia, and pneumonitis, when they needed to choose an aromatase inhibitor plus mammalian target of rapamycin (mTOR) inhibitor for advanced breast cancer treatments after failure of standard treatments. They valued exemestane alone more than exemestane plus everolimus. PMID- 26558178 TI - A comparative study between intravenous and oral alendronate administration for the treatment of osteoporosis. AB - It has recently been reported that bisphosphonates are the most common treatment for osteoporotic patients. However, they are many problems, including poor bioavailability and adherence, as well as adverse drug reactions. Therefore, intravenous administration of bisphosphonates has been developed to resolve these problems. In Japan today, alendronate and ibandronate have been approved for intravenous administration, and they have advantages, such as good adherence and better gastrointestinal tolerability, compared to oral administration. We attempted to confirm the effects of administration of intravenous alendronate, which is not inferior to oral administration, for osteoporotic patients in earlier research. 200 consecutive Japanese over 70 years-old postmenopausal women who visited the first author's orthopedic clinic and had femoral neck or lumbar spine bone mineral density (BMD) values more than 2.5 SD lower than the reference values were randomly enrolled in this study. 100 subjects were recruited for administration of intravenous alendronates because of their poor adherence, no respond of treatment status, and gastrointestinal adverse effects. Furthermore, 10 of these subjects were excluded due to discontinuation, and a total of 90 subjects were eligible for the intravenous group. The remaining 50 patients received oral alendronate. The present study also showed no significant difference between intravenous and oral administration with respect to BMD, biochemical bone turnover markers, and the incidence of fractures. These results show that intravenous administration of alendronate is not inferior to oral alendronate for the treatment of osteoporosis. Therefore, intravenous administration of alendronate can be recommended if patients do not tolerate or adhere to oral bisphosphonates. PMID- 26558179 TI - Influence of burnout and sleep difficulties on the quality of life among medical students. AB - This study assessed the influence of burnout dimensions and sleep difficulties on the quality of life among preclinical-phase medical school students. Data were collected from 193 students through their completion of the World Health Organization Quality of Life Instrument, the Maslach Burnout Inventory-Student Survey, the Mini-Sleep Questionnaire, the Social Readjustment Rating Scale, and the Beck Depression Inventory. This survey performed hierarchical multiple regressions to quantify the effects of emotional exhaustion, cynicism, academic efficacy, and sleep difficulties on the physical, psychological, social, and environmental components of an individual's quality of life. The influence of confounding variables, such as gender, stress load, and depressive symptoms, were controlled in the statistical analyses. Physical health decreased when emotional exhaustion and sleep difficulties increased. Psychological well-being also decreased when cynicism and sleep difficulties increased. Burnout and sleep difficulties together explained 22 and 21 % of the variance in the physical and psychological well-being, respectively. On the other hand, physical health, psychological well-being, and social relationships increased when the sense of academic efficacy increased. Physical and psychological well-being are negatively associated with emotional exhaustion, cynicism, and sleep difficulties in students in the early phase of medical school. To improve the quality of life of these students, a significant effort should be directed towards burnout and sleep difficulties. PMID- 26558180 TI - Towards a simple mathematical theory of citation distributions. AB - The paper is written with the assumption that the purpose of a mathematical theory of citation is to explain bibliometric regularities at the level of mathematical formalism. A mathematical formalism is proposed for the appearance of power law distributions in social citation systems. The principal contributions of this paper are an axiomatic characterization of citation distributions in terms of the Ekeland variational principle and a mathematical exploration of the power law nature of citation distributions. Apart from its inherent value in providing a better understanding of the mathematical underpinnings of bibliometric models, such an approach can be used to derive a citation distribution from first principles. PMID- 26558181 TI - Step by step approach to rare breast lesions containing spindle cells. AB - Differential diagnosis of spindle cell lesions of breast is challenging for certain reasons. The most important reason is the presence of cytological atypia and mitosis in all three conditions: reactive, benign, and malignant. Patients diagnosed with benign and malignant tumor/tumor-like lesions that had spindle cell components following the histopathological examination were included in the study. The patients' medical records were accessed to obtain the clinical history, follow-up notes, and radiological findings. Following histopathological, immunohistochemical, and clinical evaluations, the patients were diagnosed as follows: pseudoangiomatous stromal hyperplasia (PASH), bilateral desmoid-type fibromatosis (FM), adenomyoepithelioma (AME), myofibroblastoma (MFB), malignant phyllodes tumor (MF), high-grade AS, post-chemotherapy osteosarcoma (OS) + Paget's disease, and metaplastic carcinoma (MC). An algorithmic approach should be used in the diagnosis; cellular structure, presence and grade of atypia, growth pattern, mitotic activity, immunohistochemical staining, and clinical and radiological features should be evaluated together. Detection of some molecular changes can be useful in differential diagnosis. PMID- 26558182 TI - Mathematical modeling of a multi-product EMQ model with an enhanced end items issuing policy and failures in rework. AB - This study uses mathematical modeling to examine a multi-product economic manufacturing quantity (EMQ) model with an enhanced end items issuing policy and rework failures. We assume that a multi-product EMQ model randomly generates nonconforming items. All of the defective are reworked, but a certain portion fails and becomes scraps. When rework process ends and the entire lot of each product is quality assured, a cost reduction n + 1 end items issuing policy is used to transport finished items of each product. As a result, a closed-form optimal production cycle time is obtained. A numerical example demonstrates the practical usage of our result and confirms a significant savings in stock holding and overall production costs as compared to that of a prior work (Chiu et al. in J Sci Ind Res India, 72:435-440 2013) in the literature. PMID- 26558183 TI - Efficacy of sub lethal concentration of entomopathogenic fungi on the feeding and reproduction of Spodoptera litura. AB - In the present investigation, impact of sub lethal concentrations of entomopathogenic fungi, namely Isaria fumosorosea, Beauveria bassiana and Paecilomyces variotii, secondary metabolite on feeding, growth, fecundity and hatchability of Spodoptera litura was performed. The S. litura treated with I. fumosorosea and B. bassiana metabolites exhibited renounced food consumption. The growth rate of treated S. litura with metabolite of I. fumosorosea had drastic reduction. In the case of approximate digestibility (AD), maximum impact was established by the I. fumosorosea isolate, which significantly reduced the approximate digestibility of the IV and V instar larvae. The III instar larvae of S. litura treated with I. fumosorosea metabolite showed significantly lower efficiency of conversion of digested food (ECD) and efficiency of conversion of ingested food (ECI) values than IV and V instars. However the performance of metabolites on fecundity and hatchability of S. litura was immense. Therefore, metabolites of I. fumosorosea could be reliable biocontrol agent, which has been highly recommended for S. litura management in commercial crops. PMID- 26558184 TI - Changing picture of renal cortical necrosis in acute kidney injury in developing country. AB - Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients. PMID- 26558185 TI - Biomarkers in kidney transplantation: From bench to bedside. AB - Immunosuppressive drug level monitoring and serum creatinine are widely used for kidney transplantation (KT) monitoring. Monitoring of drug level is not the direct measurement of the immune response while the rising of creatinine is too late for detection of allograft injury. Kidney biopsy, the gold standard for KT monitoring, is invasive and may lead to complications. Many biomarkers have been discovered for direct monitoring of the immune system in KT and the benefit of some biomarkers has reached clinical level. In order to use biomarkers for KT monitoring, physicians have to understand the biology including kinetics of each marker. This can guide biomarker selection for specific condition. Herein, we summarize the recent findings of donor specific anti-human leukocyte antigen antibody, B lymphocyte stimulator, interferon-gamma induced protein of 10 kDa, and intracellular adenosine triphosphate monitoring, all of which have very strong evidence support for the clinical use in KT. PMID- 26558186 TI - Medical and alternative therapies in urinary tract stone disease. AB - Nephrolithiasis is a serious problem for both patients and the health system. Recurrence stands out as a significant problem in urinary system stone disease, the prevalence of which is increasing gradually. If recurrence is not prevented, patients may go through recurrent operations due to nephrolithiasis. While classical therapeutic options are available for all stone types, the number of randomized controlled studies and extensive meta-analyses focusing on their efficiency are inadequate. Various alternative therapeutic options to these medical therapies also stand out in recent years. The etiology of urolithiasis is multifactorial and not always related to nutritional factors. Nutrition therapy seems to be useful, either along with pharmacological therapy or as a monotherapy. General nutrition guidelines are useful in promoting public health and developing nutrition plans that reduce the risk or attenuate the effects of diseases affected by nutrition. Nutrition therapy involves the evaluation of a patient's nutritional state and intake, the diagnosis of nutrition risk factors, and the organization and application of a nutrition program. The main target is the reduction or prevention of calculus formation and growth via decreasing lithogenic risk factors and increasing lithogenic inhibitors in urine. This review focuses briefly on classical medical therapy, along with alternative options, related diets, and medical expulsive therapy. PMID- 26558187 TI - Pre-treatment considerations in childhood hypertension due to chronic kidney disease. AB - Hypertension (HTN) develops very early in childhood chronic kidney disease (CKD). It is linked with rapid progression of kidney disease, increased morbidity and mortality hence the imperative to start anti-hypertensive medication when blood pressure (BP) is persistently > 90(th) percentile for age, gender, and height in non-dialyzing hypertensive children with CKD. HTN pathomechanism in CKD is multifactorial and complexly interwoven. The patient with CKD-associated HTN needs to be carefully evaluated for co-morbidities that frequently alter the course of the disease as successful treatment of HTN in CKD goes beyond life style modification and anti-hypertensive therapy alone. Chronic anaemia, volume overload, endothelial dysfunction, arterial media calcification, and metabolic derangements like secondary hyperparathyroidism, hyperphosphataemia, and calcitriol deficiency are a few co-morbidities that may cause or worsen HTN in CKD. It is important to know if the HTN is caused or made worse by the toxic effects of medications like erythropoietin, cyclosporine, tacrolimus, corticosteroids and non-steroidal anti-inflammatory drugs. Poor treatment response may be due to any of these co-morbidities and medications. A satisfactory hypertensive CKD outcome, therefore, depends very much on identifying and managing these co-morbid conditions and HTN promoting medications promptly and appropriately. This review attempts to point attention to factors that may affect successful treatment of the hypertensive CKD child and how to attain the desired therapeutic BP target. PMID- 26558190 TI - Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy. AB - Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady's TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID- 26558189 TI - When to initiate renal replacement therapy: The trend of dialysis initiation. AB - The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation until 2010, at which point it decreased slightly for the following 2 years. In the 1990s, nephrologists believed that early initiation of dialysis could improve patient survival. Based on the Canadian-United States Peritoneal Dialysis study, the National Kidney Foundation Dialysis Outcomes Quality Initiative recommended that dialysis should be initiated early. Since 2001, several observational studies and 1 randomized controlled trial have found no beneficial effect when patients were placed on dialysis early. In contrast, they found that an increase in mortality was associated with early dialysis initiation. The most recent dialysis initiation guidelines recommend that dialysis should be initiated at an estimated glomerular filtration rate (eGFR) of greater than or equal to 6 mL/min per 1.73 m(2). Nevertheless, the decision to start dialysis is mainly based on a predefined eGFR value, and no convincing evidence has demonstrated that patients would benefit from early dialysis initiation as indicated by the eGFR. Even today, the optimal dialysis initiation time remains unknown. The decision of when to start dialysis should be based on careful clinical evaluation. PMID- 26558188 TI - Hepatorenal syndrome: Update on diagnosis and treatment. AB - Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome (HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice. PMID- 26558191 TI - A novel FBN1 missense mutation (p.C102Y) associated with ectopia lentis syndrome in a Chinese family. AB - AIM: To characterize the disease-causing mutations in a Chinese family with ectopia lentis syndrome (ELS). METHODS: Patients and their family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA samples were extracted from the peripheral blood of the pedigree members and 100 healthy controls. Mutation screening was performed in the fibrillin-1 (FBN1) gene by bi-directional sequencing of the amplified products. The mutation was analyzed using two bioinformatics methods. RESULTS: A novel heterozygous c.305G>A mutation in exon 3 of FBN1 was detected. As a result of this change, a highly conserved cysteine residue was replaced by a tyrosine residue (p.C102Y). Another mutation was found in the same exon (c.303T>C), which did not change the amino acid sequence. Both mutations were discovered in each affected individual, but not in the unaffected family members, or in 100 ethnically matched controls. A bioinformatics analysis predicted that mutation p.C102Y would affect protein function. CONCLUSION: In the first epidermal growth factor-like module, we identified a novel FBN1 mutation (p.C102Y), which caused ELS in the family. Our study presented a unique phenotype, including some distinct ophthalmic findings, such as hypoplasia of the iris and anisometropia. Our results expanded the mutation spectrum of FBN1 and enriched the overall knowledge of genotype phenotype correlations due to FBN1 mutations. PMID- 26558192 TI - Efficacy of the nucleotide-binding oligomerzation domain 1 inhibitor Nodinhibit-1 on corneal alkali burns in rats. AB - AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METHODS: The alkali burned rat corneas (32 right eyes) were treated with eye drops containing Nodinhibit-1 or phosphate buffered solution (PBS, PH 7.4) only, four times per day. CNV and inflammation were monitored using slit lamp microscopy, and the area of CNV was measured by formula. Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was determined by Western blot analysis. The TUNEL assay was used to assess the corneal apoptosis cells. RESULTS: Alkali burn-induced progressive CNV and inflammation in the cornea. After treatment for 7d and 14d, there were statistically significant differences in the CNV areas and inflammatory index on that between two group(P<0.05, respectively). Epithelial defect quantification showed a significant difference between the two groups at days 4 and 7 after the alkali burns (P<0.05). The apoptotic cells on days 1, 4, and 7 between the two groups showed significant differences at all time points (P<0.05, respectively). Compared to that in control group, the protein level of VEGF expression was significantly reduced whereas the PEDF expression was increase in the Nodinhibit-1 groups on day 14 (P<0.05, respectively). CONCLUSION: Topical application of 10.0 ug/mL Nodinhibit-1 may have potential effect for the alkali burn-induced CNV and inflammation. The effect of Nodinhibit-1 on CNV may be by regulation the equilibrium of VEGF and PEDF in the wounded cornea. PMID- 26558193 TI - Expression of vitamin D receptor and cathelicidin in human corneal epithelium cells during fusarium solani infection. AB - AIM: To observe the expression of vitamin D receptor (VDR) in human specimen and immortalized human corneal epithelium cells (HCEC) when challenged with fusarium solani. Moreover, we decided to discover the pathway of VDR expression. Also, we would like to detect the expression of cathelicidin antimicrobial peptide (CAMP) in the downstream pathway of VDR. METHODS: Immunohistochemistry was used to examine the VDR expression in HCEC from healthy and fungal keratitis patients. Real time quantitative polymerase chain reaction (qPCR) was performed to observe the messenger ribonucleic acid (mRNA) change of VDR when immortalized HCEC were challenged with fusarium solani for different hours. CAMP was detected at both mRNA and protein levels. RESULTS: We found out that the VDR expression in fusarium solani keratitis patients' specimen was much more than that in healthy people. The mRNA and protein expression of VDR increased when we stimulated HCEC with fusarium solani antigen (P<0.01) and it could be inhibited by toll like receptor 2 (TLR2) monoclonal antibody. The CAMP expression was decreased because of fusarium solani antigen stimulation (P<0.01). CONCLUSION: The VDR expression can be increased via TLR2/1-VDR pathway while the CAMP expression is decreased by the stimulation of fusarium solani antigen. PMID- 26558194 TI - Expression of transcription factors Slug in the lens epithelial cells undergoing epithelial-mesenchymal transition induced by connective tissue growth factor. AB - AIM: To investigate the expression of transcription factors Slug in human lens epithelial cells (HLECs) undergoing epithelial-mesenchymal transition (EMT) induced by connective tissue growth factor (CTGF). METHODS: HLECs were treated with CTGF of different concentrations (20, 50 and 100 ng/mL) or without CTGF (control) for 24h. The morphological changes of HLECs were analysed by microscopy. The expression and cellular localization of Slug was evaluated by immumo-fluorescence. Expressions of Slug, E-cadherin and alpha smooth muscle actin (alpha-SMA) were further determined by Western blot analysis. RESULTS: HLECs showed spidle fibrolasts-like characteristics and loosely connected each other after CTGF treatment. The immuno-fluorescence staining indicated that Slug was localized in the nuclei and its expression was induced by CTGF. The relative expressions of Slug protein were 1.64+/-0.11, 1.96 +/-0.03, 3.12 +/-0.10, and 4.08+/-0.14, respectively, in response to control group and treatment with CTGF of 20, 50 and 100 ng/mL (F=443.86, P<0.01). The increased Slug protein levels were correlated well with up-expression of alpha-SMA (0.78+/-0.05, 0.85+/-0.06, 2.17+/-0.15, 2.86+/-0.10; F=449.85, P<0.01) and down-expression of E-cadherin (2.50+/-0.11, 1.79+/-0.26, 1.05+/-0.14, 0.63+/-0.08; F=101.55, P<0.01). CONCLUSION: Transcription factor Slug may be involved in EMT of HLECs induced by CTGF in vitro. PMID- 26558195 TI - Small interfering RNA targeting PGC-1alpha inhibits VEGF expression and tube formation in human retinal vascular endothelial cells. AB - AIM: To determine whether small interfering RNA (siRNA) of PGC-1alpha could inhibit vascular endothelial growth factor (VEGF) expression and tube formation in human retinal vascular endothelial cells (hRVECs). METHODS: hRVECs transfected with peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC 1alpha) siRNA were incubated for 24h and then placed into a normoxic (20%, O2) or hypoxic (1%, O2) environment for another 16h. PGC-1alpha mRNA and protein levels were detected by real-time PCR and Western blot. VEGF mRNA and protein levels were detected by real-time PCR and ELISA. Cell proliferation was evaluated by BrdU incorporation assay. Forty-eight hours after siRNA transfection, hRVECs were planted into Matrigel-coated plates and cultured under normoxic (20%, O2) or hypoxic (1%, O2) conditions for another 48h. The tube formation of hRVECs was observed under an optical microscope and quantified by counting the number of branch points and calculating the total tube length. RESULTS: PGC-1alpha mRNA and protein levels were significantly reduced by PGC-1alpha siRNA, and VEGF mRNA and protein levels also decreased significantly. The percentage of BrdU-labeled cells in siPGC-1alpha groups were significantly decreased compared with control siRNA groups under normoxia and hypoxia in cell proliferation assay. In the tube formation assay, PGC-1alpha siRNA treated cells formed significantly fewer tubes. CONCLUSION: Blocking PGC-1alpha expression can inhibit VEGF expression in hRVECs and inhibit their ability to form tubes under both normoxic and hypoxic conditions. PMID- 26558196 TI - The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice. AB - AIM: To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE(+/-) mice (AChE knockout mice) of various ages. METHODS: Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 umol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE(+/-) mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer. RESULTS: Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE(+/-) mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE(+/-) mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05). CONCLUSION: In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina. PMID- 26558197 TI - Protein tyrosine phosphatase 1B regulates migration of ARPE-19 cells through EGFR/ERK signaling pathway. AB - AIM: To evaluate whether protein tyrosine phosphatase 1B (PTP1B) contributed to initiate human retinal pigment epithelium cells (A)-19 migration and investigate the signaling pathways involved in this process. METHODS: ARPE-19 cells were cultured and treated with the siRNA-PTP1B. Expression of PTP1B was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). AG1478 [a selective inhibitor of epidermal growth factor receptor (EGFR)] and PD98059 (a specific inhibitor of the activation of mitogen-activated protein kinase) were used to help to determine the PTP1B signaling mechanism. Western blot analysis verified expression of EGFR and extracellular signal-regulated kinase (ERK) in ARPE-19 cells. The effect of siRNA-PTP1B on cell differentiation was confirmed by immunostaining for alpha-smooth muscle actin (alpha-SMA) and qRT-PCR. Cell migration ability was analyzed by transwell chamber assay. RESULTS: The mRNA levels of PTP1B were reduced by siRNA-PTP1B as determined by qRT-PCR assay. SiRNA PTP1B activated EGFR and ERK phosphorylation. alpha-SMA staining and qRT-PCR assay demonstrated that siRNA-PTP1B induced retinal pigment epithelium (RPE) cells to differentiate toward better contractility and motility. Transwell chamber assay proved that PTP1B inhibition improved migration activity of RPE cells. Treatment with AG1478 and PD98059 abolished siRNA-PTP1B-induced activation of EGFR and ERK, alpha-SMA expression and cell migration. CONCLUSION: PTP1B inhibition promoted myofibroblast differentiation and migration of ARPE-19 cells, and EGFR/ERK signaling pathway played important role in migration process. PMID- 26558198 TI - Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats. AB - AIM: To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. METHODS: The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b wave and photopic negative response (PhNR) were compared between groups. RESULTS: The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. CONCLUSION: In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats. PMID- 26558199 TI - Effects of 530 nm monochromatic light on basic fibroblast growth factor and transforming growth factor-beta1 expression in Muller cells. AB - AIM: To expose rat retinal Muller cells to 530 nm monochromatic light and investigate the influence of varying light illumination times on basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) expression. METHODS: Three groups of rat retinal Muller cells cultured in vitro under a 530 nm monochromatic light were divided into 6, 12 and 24h experimental groups, while cells incubated under dark conditions served as the control group. The bFGF and TGF-beta1 mRNA expression, protein levels and fluorescence intensity of the Muller cells were analyzed. RESULTS: The bFGF mRNA expression and protein levels were significantly upregulated in Muller cells in all three experimental groups compared with the control group (P<0.05), while that of TGF-beta1 was downregulated (P<0.05). Also, bFGF expression was positively correlated, but TGF beta1 expression was negatively correlated with illumination time. The largest changes for both cytokines were seen in the 24h group. The changes in bFGF and TGF-beta1 fluorescence intensity were highest in the 24h group, and significant differences were observed among the experimental groups (P<0.05). CONCLUSION: The expressions of bFGF and TGF-beta1 changed in a time-dependent manner in Muller cells exposed to 530 nm monochromatic light with 250 lx illumination intensity. Muller cells might play a role in the development of myopia by increasing bFGF expression or decreasing TGF-beta1 expression. Changes in cytokine expression in retinal Muller cells may affect monochromatic light-induced myopia. PMID- 26558200 TI - Achromatopsia caused by novel missense mutations in the CNGA3 gene. AB - AIM: To identify the genetic defects in a Chinese family with achromatopsia. METHODS: A 2.5-year-old boy, who displayed nystagmus, photophobia, and hyperopia since early infancy, was clinically evaluated. To further confirm and localize the causative mutations in this family, targeted region capture and next generation sequencing of candidate genes, such as CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H were performed using a custom-made capture array. RESULTS: Slit-lamp examination showed no specific findings in the anterior segments. The optic discs and maculae were normal on fundoscopy. The unaffected family members reported no ocular complaints. Clinical signs and symptoms were consistent with a clinical impression of autosomal recessive achromatopsia. The results of sequence analysis revealed two novel missense mutations in CNGA3, c.633T>A (p.D211E) and c.1006G>T (p.V336F), with an autosomal recessive mode of inheritance. CONCLUSION: Genetic analysis of a Chinese family confirmed the clinical diagnosis of achromatopsia. Two novel mutations were identified in CNGA3, which extended the mutation spectrum of this disorder. PMID- 26558201 TI - Combined pars plana vitrectomy and Baerveldt glaucoma implant placement for refractory glaucoma. AB - AIM: To evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma. METHODS: The medical records of 92 eyes (89 patients) that underwent PPV-BGI were retrospectively reviewed, including 43 eyes with neovascular glaucoma (NVG) and 49 eyes with other types of glaucoma (non-NVG). RESULTS: Outcome measures were visual acuity (VA), intraocular pressure (IOP), glaucoma medical therapy, complications, and success [VA>hand motions (HM), IOP>=6 mm Hg and <=21 mm Hg, no subsequent glaucoma surgery]. Cumulative success rates for the non-NVG group and NVG group were 79% and 40% at 1y, respectively (P=0.038). No difference in the rates of surgical success were found between pars plana and anterior chamber tube placement. Preoperative IOP (mean+/-SD) was 30.3+/-11.7 mm Hg in the Non-NVG group and 40.0+/-10.6 mm Hg in the NVG group, and IOP was reduced to 15+/-9.5 mm Hg in the non-NVG group and 15+/-10.5 mm Hg in the NVG at 1y. Number of glaucoma medications (mean+/-SD) decreased from 2.7+/-1.3 in the non-NVG group and 2.8+/ 1.3 in the NVG group preoperatively to 0.76+/-1.18 in the non-NVG group and 0.51+/-1.00 in the NVG group at 1y. Improvement in VA of >=2 Snellen lines was observed in 25 (27%) eyes, although only 33% of non-NVG eyes and 2.3% of NVG eyes maintained VA better than 20/200 at 1y. Nonclearing vitreous hemorrhage was the most common postoperative complication occurring in 16 (17%) eyes, and postoperative suprachoroidal hemorrhages developed in 5 (5.4%) eyes. CONCLUSION: PPV-BGI is a viable surgical option for eyes with refractory glaucoma, but visual outcomes are frequently poor because of ocular comorbidities, especially in eyes with NVG. The location of tube placement does not influence surgical outcome and should be left to the discretion of the surgeon. PMID- 26558202 TI - Presence of Fleischer ring and prominent corneal nerves in keratoconus relatives and normal controls. AB - AIM: To examine the occurrence of commonly known clinical signs of keratoconus (KC), i.e. Fleischer ring, prominent corneal nerves and thinning, among unaffected family members of KC patients and healthy control individuals. METHODS: Data of both eyes of 117 relatives of KC patients having no manifest disease based on videokeratography indices (KC relatives), and 142 controls were used for Pearson correlation and t-test statistics. Correlation of Fleischer ring, prominent corneal nerves and central pachymetry data were tested with each other and with videokeratography indices (KSI, KISA, 3 and 6 mm Fourier asymmetry, and I-S). RESULTS: A moderate correlation was found between Fleischer ring and all examined topographical indices. Most important correlation was present with 6 mm Fourier asymmetry, and corneal pachymetry (r=0.272, P<0.001; r= 0.234, P=0.027, respectively). Similar correlations were found with prominent corneal nerves (r=0.234, P<0.001 for 6 mm Fourier asymmetry and r=-0.235, P=0.0265 for pachymetry). KC family members who exhibited Fleischer ring or prominent nerves had thinner and more asymmetric corneas than those without Fleischer ring or prominent corneal nerves (P<0.05 for pachymetry and topographic indices with t-test and Mann-Whitney rank sum test). Though rarely, Fleischer ring and prominent corneal nerves occurred among normal controls, indicating the existence of forme fruste cases in the normal population. Control subjects, who had corneal Fleischer ring or prominent nerves had corneas more similar to KC than other controls (t-test: increased KSI and KISA, P=0.048 and 0.012, respectively). CONCLUSION: In KC family members and healthy individuals, Fleischer ring and prominent corneal nerves are associated with features of KC and may suggest a possibility of forme fruste KC. Searching for the possible presence of Fleischer ring or prominent nerves on the cornea may help in the decision whether or not to diagnose subclinical KC in a borderline case. PMID- 26558203 TI - A new multiple noncontinuous puncture (pointage) technique for corneal tattooing. AB - AIM: To assess the safety and cosmetic efficacy of a new multiple noncontinuous transepithelial puncture technique for tattooing a decompensated cornea. METHODS: It was a non-comparative clinical case series study. The study examines 33 eyes in 33 patients with total corneal opacity due to corneal decompensation, which developed following intraocular surgery. Corneal tattooing was performed using the multiple noncontinuous transepithelial puncture technique (i.e. pointage). The safety of this new surgical strategy was assessed by occurrence of adverse events for the follow-up period. The cosmetic efficacy was determined by the patient's cosmetic satisfaction and independent observer's opinion about patient appearance. RESULTS: Seven women and 26 men were included in the study. The mean age was 46.4+/-17.5y (range: 7-67). In total, 30 of 33 patients (91%) reported cosmetic satisfaction within the follow-up period. Only 3 patients (9%) required additional tattooing due to cosmetic unsatisfaction. Cosmetic outcomes were analyzed and classified as excellent or good in 13 (39%) and 17 (52%) patients, respectively. No serious adverse events developed, except delayed epithelial healing in 3 cases. CONCLUSION: The cosmetic outcomes of the multiple noncontinuous transepithelial puncture technique for corneal tattooing were good. The safety of this method is higher than conventional procedures. This new procedure also provides improved cost-effectiveness and safety over current corneal tattooing techniques. PMID- 26558204 TI - Risk factors of regression and undercorrection in photorefractive keratectomy: a case-control study. AB - AIM: To determine risk factors of regression and undercorrection following photorefractive keratectomy (PRK) in myopia or myopic astigmatism. METHODS: A case-control study was designed in which eyes with an indication for re-treatment (RT) were defined as cases; primary criteria for RT indication, as assessed at least 9mo postoperatively, included an uncorrected distance visual acuity (UDVA) of 20/30 or worse and a stable refraction for more than 3mo. Additional considerations included optical quality symptoms and significant higher order aberrations (HOAs). Controls were chosen from the same cohort of operated eyes which had complete post-operative follow up data beyond 9mo and did not need RT. The cohort included patients who had undergone PRK by the Tissue-Saving (TS) ablation profile of Technolas 217z100 excimer laser (Bausch & Lomb, Rochester, NY, USA). Mitomycin C had been used in all of the primary procedures. RESULTS: We had 70 case eyes and 158 control eyes, and they were comparable in terms of age, sex and follow-up time (P values: 0.58, 1.00 and 0.89, respectively). Pre operative spherical equivalent of more than -5.00 diopter (D), intended optical zone (OZ) diameter of less than 6.00 mm and ocular fixation instability during laser ablation were associated with RT indications (all P values <0.001). These factors maintained their significance in the multiple logistic regression model with odd ratios of 6.12, 6.71 and 7.89, respectively. CONCLUSION: Higher refractive correction (>-5.00 D), smaller OZ (<6.00 mm) and unstable fixation during laser ablation of PRK for myopia and myopic astigmatism were found to be strong predictors of undercorrection and regression. PMID- 26558205 TI - Toxic keratopathy associated with abuse of topical anesthetics and amniotic membrane transplantation for treatment. AB - AIM: To evaluate the clinical findings of toxic keratopathy associated with abuse of topical anesthetics and the treatment efficacy of amniotic membrane transplantation (AMT). METHODS: Fifteen eyes of 10 patients with abuse of topical anesthetics were included in this study. The data collected included patients' demographic information, initial best corrected visual acuity (BCVA), clinical findings, time to AMT, duration of epithelization, additional treatments, posttreatment BCVA, and the results of psychiatric examination. RESULTS: All patients were male, with the mean age of 37.9+/-5.4y. The patients had received 0.5% proparacaine hydrochloride due to pain resulting from foreign bodies, such as welding flash burns and car battery explosions, for a mean of 18.2+/-12.4d. The mean initial BCVA of the patients was 0.069+/-0.100. All patients had persistent epithelial defects, stromal infiltration, ring ulcer, and corneal edema. Initially, medical treatment was attempted in all cases. Because of severe pain, persistent epithelial defects and progressing stromal thinning did not improve with medical treatment, thus, the patients underwent AMT. The mean posttreatment BCVA of the patients was 0.33+/-0.27. All of them, except for two patients, showed improved visual acuity. One patient underwent evisceration for corneal melting and endophthalmitis in another center, and one patient underwent evisceration for severe pain of unknown origin. All 5 patients who consented to a psychiatric examination had depression, had personality disorder, and used tobacco. CONCLUSION: AMT appears to be an effective method for pain relief, rapid epithelial and stromal healing; however, visual prognosis is still poor despite medical and surgical interventions. PMID- 26558206 TI - Comparison of brimonidine-timolol and dorzolamide-timolol in the management of intraocular pressure increase after phacoemulsification. AB - AIM: To compare the effectiveness of brimonidine/timolol fixed combination (BTFC) and dorzolamide/timolol fixed combination (DTFC) in the management of short-term intraocular pressure (IOP) increase after phacoemulsification surgery. METHODS: Eighty eyes of 80 patients undergoing phacoemulsification and intraocular lens (IOL) implantation were randomly assigned into three groups. Group 1 consisted of 28 eyes and represented the control group. Group 2 consisted of 25 eyes undergoing phacoemulsification surgery and BTFC was instilled at the end of surgery. Group 3 consisted of 27 eyes undergoing phacoemulsification surgery and DTFC was instilled at the end of surgery. IOP was measured preoperatively and 6, 24h and 1wk postoperatively. RESULTS: There was no statistically significant difference in preoperative baseline IOP among the three groups (P=0.84). However, IOP was significantly lower in groups 2 and 3 compared to the control group (P<0.05 for all comparisons) at all postoperative visits. There was no significant difference between groups 2 and 3 at any visit. Eight eyes (28.6%) in the control group, two (8%) in Group 2 and one (3.7%) in Group 3 had IOP >25 mm Hg at 6h after surgery (P=0.008). However, IOP decreased and was >25 mm Hg in only one eye in each group at 24h after surgery. CONCLUSION: BTFC and DTFC have similar effects in reducing increases in IOP after phacoemulsification surgery and can both be recommended for preventing IOP spikes after such surgery. PMID- 26558207 TI - Management of hypotony and flat anterior chamber associated with glaucoma filtration surgery. AB - AIM: To determine the effectiveness of pharmacological and interventional treatment of hypotony and flat anterior chamber (FAC) resulting from glaucoma filtration surgery. METHODS: We retrospectively examined the medical records of fifty-two trabeculectomy patients (52 eyes) who developed postoperative hypotony and FAC. The management and associated complications of hypotony, changing intraocular pressure (IOP) and best corrected visual acuity (BCVA) were evaluated. RESULT: Of the 52 patients with hypotony, 29 (56%) had a grade 1 FAC, 21 (40%) had a grade 2 FAC, and only 2 had a grade 3 FAC. There was no significant difference between the mean preoperative IOP and the mean IOP at three and six months after surgery. Thirteen eyes (25%) required antiglaucomatous medication three months after surgery. The mean BCVA at 6mo after surgery was significantly reduced as compared with the mean preoperative BCVA. CONCLUSION: Hypotonia and FAC following trabeculectomy are associated with troublesome complications that require pharmacological and/or surgical treatment. Thus, close follow-up is essential for affected patients. PMID- 26558208 TI - Effects of primary selective laser trabeculoplasty on anterior segment parameters. AB - AIM: To investigate the effects of selective laser trabeculoplasty (SLT) on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG). METHODS: Pentacam measurements of 45 eyes of 25 (15 females and 10 males) patients (12 with OHT, 13 with POAG) before and after SLT were obtained. Measurements were taken before and 1 and 3mo after SLT. Pentacam parameters were compared between OHT and POAG patients, and age groups (60y and older, and younger than 60y). RESULTS: The mean age of the patients was 57.8+/-13.9 (range 20-77y). Twelve patients (48%) were younger than 60y, while 13 patients (52%) were 60y and older. Measurements of pre-SLT and post-SLT 1mo were significantly different for the parameters of central corneal thickness (CCT) and anterior chamber volume (ACV) (P<0.05). These parameters returned back to pre-SLT values at post-SLT 3mo. Decrease of ACV at post-SLT 1mo was significantly higher in younger than 60y group than 60y and older group. There was no statistically significant difference in Pentacam parameters between OHT and POAG patients at pre- and post-treatment measurements (P>0.05). CONCLUSION: SLT leads to significant increase in CCT and decrease in ACV at the 1(st) month of the procedure. Effects of SLT on these anterior segment parameters, especially for CCT that interferes IOP measurement, should be considered to ensure accurate clinical interpretation. PMID- 26558209 TI - Long-term outcomes in patients initially responsive to selective laser trabeculoplasty. AB - AIM: To determine the long-term effects of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) and the number of medications used up to 5y following treatment in glaucoma patients receiving maximally tolerated medical therapy (MTMT). METHODS: The Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the charts of glaucoma patients who underwent SLT after receiving MTMT. Eyes that did not achieve their target pressure within 3mo following SLT were excluded from the study. Changes in mean IOP and number of glaucoma medications used were analyzed at 1, 3, and 5y following SLT. RESULTS: Seventy-five eyes of 67 patients were included in the study. Fifteen eyes that received SLT failed to achieve their target pressure within 3mo and were excluded from the study. The average follow-up time was 37.4mo (+/-14.4). Mean IOP was significantly reduced 1y after treatment (P=0.005). It was also reduced 3, 5y after treatment without reaching statistical significance (P=0.20 and P=0.072, respectively). There was a significant decrease in mean number of medications used 1, 3, 5y after treatment (P<0.001, P<0.001, and P=0.039, respectively). In the span of 5y, 2 eyes (2.7%) underwent repeat SLT, 7 eyes (9.3%) underwent glaucoma surgery and an additional 3 eyes (4.0%) underwent both. CONCLUSION: SLT significantly reduced the number of glaucoma medications used 5y following treatment in glaucoma patients receiving MTMT. SLT may delay operating-room surgery. PMID- 26558210 TI - Phacoemulsification versus small incision cataract surgery in patients with uveitis. AB - AIM: To compare the safety and efficacy of phacoemulsification and small incision cataract surgery (SICS) in patients with uveitic cataract. METHODS: In a prospective, randomized multi-centric study, consecutive patients with uveitic cataract were randomized to receive phacoemulsification or manual SICS by either of two surgeons well versed with both the techniques. A minimum inflammation free period of 3mo (defined as less than 5 cells per high power field in anterior chamber) was a pre-requisite for eligibility for surgery. Superior scleral tunnel incisions were used for both techniques. Improvement in visual acuity post operatively was the primary outcome measure and the rate of post-operative complications and surgical time were secondary outcome measures, respectively. Means of groups were compared using t-tests. One way analysis of variance (ANOVA) was used when there were more than two groups. Chi-square tests were used for proportions. Kaplan Meyer survival analysis was done and means for survival time was estimated at 95% confidence interval (CI). A P value of <0.05 was considered statistically significant. RESULTS: One hundred and twenty-six of 139 patients (90.6%) completed the 6-month follow-up. Seven patients were lost in follow up and another six excluded due to either follow-up less than six months (n=1) or inability implant an intraocular lens (IOL) because of insufficient capsular support following posterior capsule rupture (n=5). There was significant improvement in vision after both the procedures (paired t-test; P<0.001). On first postoperative day, uncorrected distance visual acuity (UDVA) was 20/63 or better in 31 (47%) patients in Phaco group and 26 (43.3%) patients in SICS group (P=0.384). The mean surgically induced astigmatism (SIA) was 0.86+/-0.34 dioptres (D) in the phacoemulsification group and 1.16+/-0.28 D in SICS group. The difference between the groups was significant (t-test, P=0.002). At 6mo, corrected distance visual acuity (CDVA) was 20/60 or better in 60 (90.9%) patients in Phaco group and 53 (88.3%) in the manual SICS group (P=0.478). The mean surgical time was significantly shorter in the manual SICS group (10.8+/-2.9 versus 13.2+/-2.6min) (P<0.001). Oral prednisolone, 1 mg/kg body weight was given 7d prior to surgery, continued post-operatively and tapered according to the inflammatory response over 4-6wk in patients with previously documented macular edema, recurrent uveitis, chronic anterior uveitis and intermediate uveitis. Rate of complications like macular edema (Chi-square, P=0.459), persistent uveitis (Chi-square, P=0.289) and posterior capsule opacification (Chi-square, P=0.474) were comparable between both the groups. CONCLUSION: Manual SICS and phacoemulsification do not differ significantly in complication rates and final CDVA outcomes. However, manual SICS is significantly faster. It may be the preferred technique in settings where surgical volume is high and access to phacoemulsification is limited, such as in eye camps. It may also be the appropriate technique for uveitic cataract under such circumstances. PMID- 26558211 TI - Results of cataract surgery in renal transplantation and hemodialysis patients. AB - AIM: To compare the effect of cataract surgery in renal transplantation and hemodialysis patients. METHODS: We evaluated 51 eyes of 31 renal transplantation patients, 41 eyes of 29 hemodialysis patients and 45 eyes of 32 normal control patients who received phacoemulsification and intraocular lens (IOL) implantation from January, 2000 to August, 2014 in the Beijing Friendship Hospital. Each individual underwent a blood routine and a kidney function examination. Routine ophthalmologic examination included best-corrected visual acuity (BCVA), a slit lamp examination to detect cataract type, determination of intraocular pressure, a corneal endothelial count, and fundus examination. All patients received phacoemulsification and an IOL implantation. RESULTS: For the types of cataract in the three groups, transplantation group was significantly different from normal control group (P=0.04), the most kind is posterior subcapsular cataract (PSC) in transplantation group 33 (64.7%), hemodialysis group had no significantly difference from normal control group (P=0.43), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.02). For postoperative BCVA in the three groups, transplantation group had significantly difference from normal control group (P=0.03), hemodialysis group was significantly different from normal control group (P=0.00), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.00). The multiple linear regression equation is Y=0.007 hemoglobin (Hb)-0.000233 serum creatinine (Cr), R(2)=0.898. Postoperative fundus examination showed that hemorrhage, exudation, and macular degeneration were greater in the hemodialysis group. CONCLUSION: This study showed that the PSC was more in the renal transplantation patients. BCVA was better and fundus lesions were less frequent in the renal transplantation group than in the hemodialysis group after cataract surgery. The multiple linear regression was showed that the Hb was positively correlated with postoperative BCVA, while Cr was negatively correlated with postoperative BCVA. These results may act as indicators in predicting visual acuity for the renal transplantation and hemodialysis patients. PMID- 26558212 TI - Diffusion tensor imaging of optic nerve and optic radiation in primary chronic angle-closure glaucoma using 3T magnetic resonance imaging. AB - AIM: To evaluate the value of quantitative diffusion tensor imaging (DTI) in assessing the axonal and myelin damage of the optic nerves and optic radiations in patients with chronic primary angle-closure glaucoma (PACG) by using high field magnetic resonance (MR) imaging (3T). METHODS: Twenty patients with bilateral chronic PACG and twenty age- and sex matched disease-free control subjects were enrolled. Conventional MRI and DTI were performed on all subjects using 3T MR scanner. Mean diffusivity (MD), fractional anisotropy (FA), axial diffusivities (AD) and radial diffusivities (RD) of each optic nerve and each optic radiation were measured by using post-processing software of DTI studio 2.3, and then compared between left eyes and right eyes and between patients group and control group. The paired-sample t- test were used. RESULTS: There was no abnormality in the shape and signal intensity of the optic nerves and optic radiations in patients group and control group on the conventional MRI. No significant differences were observed in the FA, MD, AD and RD between the right and left optic nerves and optic radiations within patients group and control group (P>0.05). The optic nerves and optic radiations of patients with chronic PACG, as compared with control subjects, had significantly higher MD, AD, RD and significantly lower FA (P<0.05). CONCLUSION: The diffusivity of optic nerves and optic radiations in chronic PACG group showed abnormal and diffusivity parameters could be used markers of axonal and myelin injury in glaucoma. PMID- 26558213 TI - Anterior segment changes after pharmacologic mydriasis using Pentacam and optical coherence tomography in angle closure suspects. AB - AIM: To compare the dynamic changes of anterior segment parameters especially iris morphology induced by pharmacologic mydriasis between angle closure suspects and normal controls. METHODS: The study group comprised 19 eyes of 19 angle closure suspects and 19 eyes of 19 age- and sex-matched normal open-angle eyes. Pentacam and optical coherence tomography measurements before and 30min after instillation of compound tropicamide eye drop were performed and compared. Biometric evaluations of iris tomography and anterior chamber angle were estimated by a customized image-processing software. RESULTS: Baseline axial length, iris cross sectional area and volume did not differ significantly between angle closure suspects and normal controls. Angle closure suspects had smaller pupil size, narrower anterior segment dimension and axial length, thinner iris with greater curve in comparison with normal controls. Pharmacologic mydriasis led to significant increments in iris thickness at 750 um, anterior chamber depth and volume, whereas significant decrements in iris curve, cross sectional area and volume in both groups. Angle opening distance at 500 um was increased significantly in normal controls (from 0.465+/-0.115 mm to 0.539+/-0.167 mm, P=0.009), but not in angle closure suspects (from 0.125+/-0.100 mm to 0.145+/ 0.131 mm, P=0.326). Iris volume change per millimeter of pupil dilation (DeltaIV/DeltaPD) decreased significantly less in angle closure suspects than normal controls (-2.47+/-1.33 mm(2) vs -3.63+/-1.58 mm(2), P=0.019). Linear regression analysis showed that the change of angle opening distance at 500 um was associated most with the change of central anterior chamber depth (beta=0.841, P=0.002) and DeltaIV/DeltaPD (beta=0.028, P=0.002), followed by gender (beta=0.062, P=0.032). CONCLUSION: Smaller iris volume decrement per millimeter of pupil dilation is related significantly with the less anterior angle opening in angle closure suspects after pharmacologic mydriasis. Dynamic iris change may be as a prospective indicator of iris compressibility and angle closure glaucoma. PMID- 26558214 TI - Total oxidative stress, paraoxonase and arylesterase levels at patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma. AB - AIM: To investigate the oxidative stress status of the aqueous humor and serum of patients with pseudoexfoliation (PEX) syndrome and pseudoexfoliative glaucoma (PEG) and to measure paraoxonase (PON) and arylesterase (ARE) levels. METHODS: A total of 78 patients were enrolled in the study, with 26 patients in each separate group. The patients were divided into three groups: the first group entailed PEX syndrome patients, while the second group consisted of patients with PEG and the third group involved patients with no additional systemic diseases, other than the diagnosis of cataract as control. Total oxidative stress (TOS), total antioxidant capacity (TAC), PON, and ARE levels in aqueous humor and serum were measured. RESULTS: TAC, PON and arylesterase levels in aqueous humor and serum of the PEX syndrome and PEG patients were significantly decreased compared with control group (P<0.05). TOS values were higher in patients with PEX syndrome and PEG than controls (P<0.05). TAC, PON and ARE levels of aqueous humor did not differ significantly between the PEX syndrome and PEG groups. CONCLUSION: These findings are potentially of significance and add to the growing body of evidence for oxidative stress in PEX syndrome and PEG. Decreased antioxidant defense and increased oxidative stress system may play an important role in the pathogenesis of PEX syndrome and PEG. PMID- 26558215 TI - Brain-derived neurotrophic factor in patients with advanced age-related macular degeneration. AB - AIM: To investigate the serum level of the brain-derived neurotrophic factor (BDNF) in age-related macular degeneration (AMD) and healthy control subjects. The disruption in the tight balance of neuroinflammatory and neuroprotective processes in an immune-privileged site like retina is proposed to contribute to the pathogenesis of AMD. One of the main neuroprotective mediators in the central nervous system is BDNF with its serum level notably affected in several neurodegenerative disorders. METHODS: Thirty-six patients with AMD and 36 age matched controls were enrolled in this study. The serum level of BDNF was measured using the enzyme-linked immunosorbent assay method. Results were analyzed to compare case and control values. Comparisons were also made between the BDNF level of wet- vs dry-AMD, and male vs female patients and controls. Analysis of variance (ANOVA) and Student's t-test were employed to analyze the data. RESULTS: The mean BDNF levels in AMD group were significantly higher than the control group. Furthermore, our analysis revealed greater BDNF values in all AMD subgroups compared to controls (P=0.004, 0.005, 0.001 and 0.02 for male wet AMD, male dry-AMD, female wet-AMD and female dry-AMD vs controls, respectively). The BDNF level however did not vary between wet- and dry-AMD patients (P=0.74). While within-group comparisons in males and females of AMD and control groups did not show any difference in BDNF (P=0.16, 0.64 and 0.85 for wet-AMD, dry-AMD and control groups, respectively), between-group data showed a higher mean BDNF in both male and female AMD subjects than their peer controls. CONCLUSION: This study demonstrated that the serum BDNF level is different in patients with AMD as compared to subjects without AMD. Future attempts should be done to unravel beneficial or deleterious effect of this neurotrophin in the pathogenesis of AMD. PMID- 26558216 TI - Characterization of human retinal vessel arborisation in normal and amblyopic eyes using multifractal analysis. AB - AIM: To characterize the human retinal vessel arborisation in normal and amblyopic eyes using multifractal geometry and lacunarity parameters. METHODS: Multifractal analysis using a box counting algorithm was carried out for a set of 12 segmented and skeletonized human retinal images, corresponding to both normal (6 images) and amblyopia states of the retina (6 images). RESULTS: It was found that the microvascular geometry of the human retina network represents geometrical multifractals, characterized through subsets of regions having different scaling properties that are not evident in the fractal analysis. Multifractal analysis of the amblyopia images (segmented and skeletonized versions) show a higher average of the generalized dimensions (Dq ) for q=0, 1, 2 indicating a higher degree of the tree-dimensional complexity associated with the human retinal microvasculature network whereas images of healthy subjects show a lower value of generalized dimensions indicating normal complexity of biostructure. On the other hand, the lacunarity analysis of the amblyopia images (segmented and skeletonized versions) show a lower average of the lacunarity parameter Lambda than the corresponding values for normal images (segmented and skeletonized versions). CONCLUSION: The multifractal and lacunarity analysis may be used as a non-invasive predictive complementary tool to distinguish amblyopic subjects from healthy subjects and hence this technique could be used for an early diagnosis of patients with amblyopia. PMID- 26558217 TI - Fundus autofluorescence in central serous chorioretinopathy: association with spectral-domain optical coherence tomography and fluorescein angiography. AB - AIM: To evaluate the correlation among changes in fundus autofluorescence (AF) measured using infrared fundus AF (IR-AF) and short-wave length fundus AF (SW-AF) with changes in spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) in central serous chorioretinopathy (CSC). METHODS: Two hundred and twenty consecutive patients with CSC were included. In addition to AF, patients were assessed by means of SD-OCT and FA. Abnormalities in images of IR-AF, SW-AF, FA were analyzed and correlated with the corresponding outer retinal alterations in SD-OCT findings. RESULTS: Eyes with abnormalities on either IR-AF or SW-AF were found in 256 eyes (58.18%), among them 256 eyes (100%) showed abnormal IR-AF, but SW-AF abnormalities were present only in 213 eyes (83.20%). The hypo-IR-AF corresponded to accumulation of sub-retinal liquid, collapse of retinal pigment epithelium (RPE) or detachment of RPE with or without RPE leakage point in the corresponding area. The hyper-IR-AF corresponded to the area with loss of the ellipsoid portion of the inner segments and sub-sensory retinal deposits or focal melanogenesis under sensory retina. The hypo-SW-AF corresponded to accumulation of sub-retinal liquid or atrophy of RPE. The hyper SW-AF associated with sub-sensory retinal deposits, detachment of RPE and focal melanogenesis. CONCLUSION: IR-AF was more sensitive than SW-AF and FA for identifying pathological abnormalities in CSC. The characteristics of IR-AF in CSC were attributable to the modification of melanin in the RPE. IR-AF should be used as a common diagnostic tool for identifying pathological lesion in CSC. PMID- 26558218 TI - Helvacioglu reproducibility index: a new algorithm to evaluate the effects of misalignments on the measurements of retinal nerve fiber layer by spectral-domain OCT. AB - AIM: To evaluate the effect of misalignment on the measurements of retinal nerve fiber layer (RNFL) by spectral-domain optical coherence tomography (OCT). METHODS: A total of 42 eyes from 21 healthy young subjects underwent RNFL measurements with RTVue spectral-domain OCT (Optovue Inc., Fremont, California, USA). Two baseline measurements with perfectly aligned central circle to the borders of the optic nerve and four misaligned measurements which were misaligned towards to four quadrants were taken. The differences in RNFL between the baseline and misaligned measurements were analyzed with a new algorithm called Helvacioglu reproducibility index (HRI) which is designed to measure the reproducibility of the scans by evaluating the RNFL changes in the four main quadrants. RESULTS: The average RNFL scores of the first two baseline measurements have good correlation (c=0.930) and good reproducibility scores (0.15+/-0.07). Superior misaligned measurements had significantly lower superior quadrant score and higher inferior quadrant score, similar nasal and little higher temporal scores (P1, P2<0.001, P3=0.553, P4=0.001). Inferior misaligned measurements had significantly higher superior quadrant score and lower inferior quadrant score with similar temporal and little lower nasal scores (P1, P2<0.001, P3=0.315, P4=0.016). Nasal misaligned measurements had significantly higher temporal quadrant score and lower nasal quadrant score with little lower superior and inferior scores (P1, P2, P4<0.001, P3=0.005). Temporal misaligned measurements had significantly higher nasal quadrant score and lower temporal quadrant score with similar superior and little higher inferior scores (P1, P2<0.001, P3=0.943, P4=0.001). CONCLUSION: Good alignment of the central circle to the borders of optic nerve is crucial to have correct and repeatable RNFL measurements. Misalignment to a quadrant resulted in falsely low readings at that quadrant and falsely high readings at the opposite quadrant. PMID- 26558219 TI - Relationship between short-wavelength automatic perimetry and Heidelberg retina tomograph parameters in eyes with ocular hypertension. AB - AIM: To compare and correlate optic nerve head parameters obtained by Heidelberg retina tomograph (HRT) with short-wavelength automatic perimetry (SWAP) indices in eyes with ocular hypertension (OHT). METHODS: One hundred and forty-six patients with OHT included in the present study. All subjects had reliable SWAP and HRT measurements performed within a 2wk period. The eyes were classified as normal/abnormal according to visual field criteria and Moorfields regression analysis (MRA). Correlations between visual field indices and HRT parameters were analyzed using Pearson correlation coefficient (r). RESULTS: Twenty-nine eyes (19.9%) had SWAP defects. Twenty-nine eyes (19.9%) were classified as abnormal according to global MRA. Six eyes (4.1%) had abnormal global MRA and SWAP defects. The k statistic is 0.116 (P=0.12) indicating a very poor agreement between the methods. No statistical significant correlation between HRT and SWAP parameters was detected. CONCLUSION: SWAP defects may coexist with abnormalities of optic disc detected by HRT in eyes with OHT. In most eyes, however, the two methods detect different glaucoma properties. PMID- 26558220 TI - Orbital metastases in Italy. AB - AIM: To describe a series of Italian patients with orbital metastasis focusing on the outcomes in relation to the different primary site of malignancy. METHODS: Retrospective chart review of 93 patients with orbital metastasis collected in a tertiary referral centre in a period of 38y and review of literature. RESULTS: Out of 93 patients, 52 were females and 41 were males. Median age at diagnosis was 51y (range 1 to 88y). The patients have been divided into four groups on the basis of the year of diagnosis. The frequency of recorded cases had decreased significantly (P<0.05) during the last 9.5y. Primary tumor site was breast in 36 cases (39%), kidney in 10 (11%), lung in 8 (9%), skin in 6 (6%); other sites were less frequent. In 16 case (17%) the primary tumor remained unknown. The most frequent clinical findings were proptosis (73%), limited ocular motility (55%), blepharoptosis (46%) and blurred vision (43%). The diagnosis were established by history, ocular and systemic evaluation, orbital imaging studies and open biopsy or fine needle aspiration biopsy (FNAB). Treatment included surgical excision, irradiation, chemotherapy, hormone therapy, or observation. Ninety-one percent of patients died of metastasis with an overall mean survival time (OMST) after the orbital diagnosis of 13.5mo. CONCLUSION: Breast, kidney and lung are the most frequent primary sites of cancer leading to an orbital metastasis. When the primary site is unknown, gastrointestinal tract should be carefully investigated. In the last decade a decrease in the frequency of orbital metastasis has been observed. Surgery provides a local palliation. Prognosis remains poor with a OMST of 13.5mo ranging from the 3mo in the lung cancer to 24mo in the kidney tumor. PMID- 26558221 TI - Removal of the eye in a tertiary care center of China: a retrospective study on 573 cases in 20 years. AB - AIM: To investigate the original protopathy, direct indications, clinical characteristics, complications of orbit plants and visual conditions of eye enucleation/evisceration. METHODS: A retrospective study of 573 eyes removed (573 inpatients) at Ophthalmology Department in a tertiary care center of China from January 1993 to December 2012 was completed. RESULTS: Cases underwent removal of the eye accounted for 2.15% of total ophthalmology inpatients, whose annual frequency declined from 3.80% to 0.52%. There were 167 eyes (29.14%) being enucleated and 406 (70.86%) eviscerated. Annual proportion of evisceration rose from 16.67% in 1993 to 90.48% in later years. Trauma was the top one (65.62%) in original protopathies followed by neoplasm (13.44%) and ocular infections (5.76%). Phthisis bulbi (45.20%) was the most common direct indication, succeeded by malignant tumor (12.57%), loss/unreconstructed of intraocular tissues due to trauma (11.00%), untreatable inflammation (9.60%), intractable glaucoma (8.55%) and sclerocorneal staphyloma (5.24%). Exenteration was underwent in 20 (25.97%) cases (40% for recurrent carcinoma). Following evisceration, secondary prosthesis implantation was more and earlier, implant exposure occurred in less but earlier and infection and extraction/exchange of implants were more than those following enucleation. Male, phthisis bulbi, evisceration and secondary implantation meant lower risk of implant exposure; eyes removed within 24h following trauma was an independent risk factor. There were 14.37% of eyes with vision of light perception at least as been removed. In the residual contralateral eyes, low vision accounted 5.58% and blindness 3.14%. CONCLUSION: Ocular trauma, tumor and infections were great threats to eyeball preservation. Early and effective controlling of any original protopathies was vital. Generally evisceration presented more superior and safe outcomes than enucleation did. Visual conditions of the sufferers should be focused on. PMID- 26558222 TI - Evaluation of patient visual comfort and repeatability of refractive values in non-presbyopic healthy eyes. AB - AIM: To evaluate the intra-operator repeatability in healthy subjects using the WAM-5500 auto-kerato/refractometer and the iTrace aberrometer, to compare the refractive values and the subjective refraction obtained with both devices and to determine which of these three spherocylindrical corrections allows the subject to achieve the best visual comfort. METHODS: Forty-two non-presbyopic healthy eyes of 42 subjects were enrolled in this prospective study. Refractive values were compared, evaluating the repeatability, the relationship between the methods and the best visual comfort obtained. RESULTS: Sphere, cylinder and axis results showed good intraclass correlation coefficients (ICC); the highest ICC was obtained using the spherical refraction with the autorefractometer and the aberrometer, achieving levels of 0.999 and 0.998, respectively. The power vector (PV) was calculated for each refraction method, and the results indicated that there were no statistically significant differences between them (P>0.05). Direct comparison of PV measurements using the three methods showed that aberrometer refraction gave the highest values, followed by the subjective values; the autorefractometer gave the lowest values. The subjective method correction was most frequently chosen as the first selection. Equal values were found for the autorefractometer and the aberrometer as the second selection. CONCLUSION: The iTrace aberrometer and the WAM-5500 auto-kerato/refractometer showed high levels of repeatability in healthy eyes. Refractive corrections with the aberrometer, the autorefractometer and subjective methods presented similar results, but spherocylindrical subjective correction was the most frequently selected option. These technologies can be used as complements in refractive evaluation, but they should not replace subjective refraction. PMID- 26558223 TI - Oxygen permeability of soft contact lenses in different pH, osmolality and buffering solution. AB - AIM: To determine the effect of pH, osmolality, and buffering system on the oxygen permeability (Dk) of soft contact lenses. METHODS: Two hydrogel lenses (nelfilcon A and etafilcon A) and 2 silicone hydrogel lenses (lotrafilcon A and balafilcon A) were used in the study. These lenses were incubated in phosphate buffered saline (PBS) and borate-buffered saline (BBS) solutions adjusted by 0.8 pH increments to a pH in the range of 5.8-9.0 or in hypotonic (280 mOsmol/kg), isotonic (310 mOsmol/kg) and hypertonic (380 mOsmol/kg) PBS solutions. Polarographic method was used for measuring the Dk and lenses were stacked as 4 layers to correct the boundary effect. RESULTS: Dk values of all contact lenses measured in BBS solutions were more stable than those in PBS solutions. Especially the etafilcon A lens showed a relative big change compared with other types of contact lenses at the same conditions. When the osmolality of PBS solution increased from hypotonic to hypertonic, Dk of all contact lenses decreased. Variations in Dk existed depending on lens materials, etafilcon A lens was the most affected and nelfilcon A was the least affected by osmolality. CONCLUSION: From the result obtained, it is revealed that Dk of contact lenses is changed by the pH, osmolality, and buffering condition of tear. Thus, Dk of contact lens can be varied by the lens wearers' physiological and/or pathological conditions. PMID- 26558224 TI - Reproducibility of optical quality parameters measured at objective and subjective best focuses in a double-pass system. AB - AIM: To evaluate intra-session repeatability and reproducibility of optical quality parameters measured at objective and subjective best focuses in a double pass system. METHODS: Thirty Chinese healthy adults (19 to 40 years old) meeting our inclusion criterion were enrolled in the study. After a basic eye examination, two methods of optical quality measurement, based on subjective and objective best focuses were performed using the Optical Quality Analysis System (OQAS) with an artificial pupil diameter of 4.0 mm. RESULTS: With each method, three consecutive measurements of the following parameters: the modulation transfer function cutoff frequency (MTFcutoff), the Strehl(2D) ratio, the OQAS values (OVs) at contrasts of 100%, 20%, 9% and the objective scatter index (OSI) were performed by an experienced examiner. The repeatability of each method was evaluated by the repeatability limit (RL) and the coefficient of repeatability (COR). Reproducibility of the two methods was evaluated by intra-class correlation coefficient (ICC) and the 95% limits of agreement (Bland and Altman analysis). Thirty subjects, seven females and twenty three males, of whom 15 right eyes and 15 left eyes were selected randomly for recruitment in the study. The RLs (percentage) for the six parameters measured at objective focus and subjective focus ranged from 8.44% to 15.13% and 10.85% to 16.26%, respectively. The CORs for the two measurement methods ranged from 8.27% to 14.83% and 10.63% to 15.93%, respectively. With regard to reproducibility, the ICCs for the six parameters of OQAS ranged from 0.024 to 0.276. The 95% limits of agreement obtained for the six parameters (in comparison of the two methods) ranged from 0.57 to 42.18 (MTFcutoff), -0.01 to 0.23 (Strehl(2D) ratio), -0.02 to 1.40 (OV100%), -0.10 to 1.75 (OV20%), -0.14 to 1.80 (OV9%) and -1.46 to 0.18 (OSI). CONCLUSION: Measurements provided by OQAS with either method showed a good repeatability. However, the results obtained from the two different measurement methods showed a poor reproducibility. These findings suggest that it might be best to evaluate patients' optical quality by OQAS using the best focus as chosen automatically by the instrument. PMID- 26558225 TI - Application of traditional indexes and adverse events in the ophthalmologic perioperative medical quality evaluation during 2010-2012. AB - AIM: To evaluate the medical quality of ophthalmologic perioperative period during 2010-2012 in our hospital. METHODS: The relevant data of perioperative period were collected in our hospital during 2010-2012, and the medical quality of perioperative period was evaluated by using the traditional evaluation indexes and adverse events. Whereby, the traditional indicators include vision changes, improving of intraocular pressure, diagnostic accordance rate before and after operation, cure improvement rate, successful rescue rate, and incidence of surgical complications, etc. Adverse events are associated with ophthalmologic perioperative events including pressure sores, postoperative wound infection, drug adverse events, and equipment related adverse events. RESULTS: There were 1483, 1662 and 1931 ophthalmic operations in our hospital in the year 2010, 2011 and 2012, respectively. From traditional index analysis, the proportions of vision improvement for each year were 96.43%, 96.76% and 97.32%, respectively; the rates of intraocular pressure improvement were 87.50%, 85.72% and 90.17%, respectively (P <0.05); the diagnostic accordance rates before and after operation were 99.86%, 99.94% and 99.90%, respectively; cure improvement rates were 99.73%, 99.93% and 99.84%, respectively; the successful rescue rates were 82.98%, 81.46% and 76.66%, respectively; the complications incidence rates were 18.44%, 17.52% and 17.97%, respectively. The negative factor analysis results showed that: among all the patients of ophthalmic surgeries in our hospital during 2010 and 2012, only one case of postoperative wound infection was found in 2011, and also only one case of tumbling in 2010. The adverse drug events for each year were 1 case (0.07%), 2 cases (0.12%), and 4 cases (0.21%), respectively; the medical device adverse events for each year were 3 cases (0.20%), 5 cases (0.30%), and 6 cases (0.31%), respectively. Noticeably, only one case with postoperative infection of endophthalmitis was found in 2011. Moreover, no pulmonary infection or pulmonary embolism occurred during the three years. The perioperative adverse event rates for each year were 0.34% (5/1483), 0.48% (8/1662) and 0.52% (10/1931), respectively. Though incidence was rising during the three years period, no statistical significance was observed (P>0.05). It is the same case with drugs and medical devices adverse events (P >0.05). CONCLUSION: Traditional indicators reflect an excellent operation of the perioperative ophthalmologic quality, whereas adverse events analysis indicates some underlying problems. Compared with the traditional indexes for medical quality evaluation, the index of adverse events is more reasonable and easier to make an objective evaluation for medical quality of ophthalmologic perioperation, facilitating further refine analysis. Reasonable application of the adverse events indicators helps hospital to make the detailed quality control measures. PMID- 26558226 TI - Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta analysis. AB - AIM: To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis. RESULTS: Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P<=0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P<0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P<0.01) after removal of a heterogeneous study. CONCLUSION: IVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first line therapy for PCV. PMID- 26558227 TI - Bare sclera resection followed by mitomycin C and/or autograft limbus conjunctiva in the surgery for pterygium: a Meta-analysis. AB - AIM: To evaluate the recurrence and complications after bare sclera resection (BSR) combined with mitomycin C (MMC) treatment and/or autograft limbus conjunctiva (ALC) in the surgery for pterygium. METHODS: Meta-analysis was used to evaluate the differences in patient outcomes between BSR of pterygium with or without MMC and/or ALC. All included studies were randomized trials of patients with pterygium who received BSR followed by MMC and/or ALC in the surgery. The recurrence of pterygium and other complications resulting from different treatments were extracted for analysis. RESULTS: Thirteen studies met the inclusion criteria. The recurrence of pterygium with intraoperative (IO) MMC was higher than that with ALC (OR=2.38, 95% confidence interval 1.45-3.91, I (2)=29%). Postoperative MMC resulted in an incidence of recurrence similar to that of ALC (OR=0.66, 95% confidence interval 0.30-1.42, I (2)=0%), and IO MMC treatment in combination with ALC produced similar patient outcomes to ALC alone (OR=0.41, 95% confidence interval 0.16-1.01, I (2)=16%). Other complications such as punctate epitheliopathy, scleral thinning and ischemia, irritation and persistent epithelium defect, were more common in patients in the MMC group as compared to those treated with ALC. CONCLUSION: The recurrence of pterygium with BSR followed by ALC is lower than that of BSR followed by MMC, and the incidence of other complications is lower. While ALC is a more effective strategy for treating pterygium, the quality of the ALC transplant should be considered when the patient has a history of glaucoma. PMID- 26558228 TI - Contact lens impact on quality of life in keratoconus patients: rigid gas permeable versus soft silicone-hydrogel keratoconus lenses. AB - AIM: To determine the impact of rigid gas permeable (RGP) and silicone-hydrogel keratoconus lenses on the quality of life (QoL) in keratoconus (KCN) patients using the self-reported results from the Contact Lens Impact on Quality of Life (CLIQ) Questionnaire. METHODS: From January 2013 to April 2013, 27 consecutive KCN patients who wore RGP contact lenses (conflexair100 UV KE Zeiss-Wohlk) or soft silicone-hydrogel contact lenses (SHCLs) for KCN (KeraSoft IC- Bausch&Lomb or Hydrocone Toris K-Swiss lens) completed the CLIQ questionnaire. RESULTS: The mean age of 27 patients was 29.6+/-8.0y. Fifteen patients were RGP user. The groups were comparable with respect to the mean patient age, sex, and mean K values (P=0.1, P=0.8 and P=0.1, respectively). The mean CLIQperson measure was 42.8+/-5.5 in RGP group and 39.6+/-5.5 in SHCLs for KCN group (P=0.06). CLIQperson measure was positively correlated with steep K value (r=0.301, P=0.04). When eyes were stratified by visual acuity with contact lenses, the mean CLIQperson measure was 42.01+/-5.6 in eyes with a visual acuity of 20/20-20/25 (n=44) and 38.4+/-5.26 in eyes with a visual acuity of 20/32 or less (n=10; P=0.097). CONCLUSION: RGP lenses and SHCLs for KCN have similar impact on QoL. PMID- 26558229 TI - Novel in-frame deletion mutation c.177_179delTAC of neurofibromatosis type 1 in a Chinese 4-year-old boy with binocular blindness. PMID- 26558230 TI - Mobile lens-induced angle closure glaucoma and rubeosis iridis in Sturge Weber syndrome. PMID- 26558231 TI - Guidance in Subclinical Hyperthyroidism and Subclinical Hypothyroidism: Are We Making Progress? PMID- 26558233 TI - Thyroid Growth and Cancer. AB - It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term 'cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID- 26558232 TI - The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism. AB - Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective reference intervals. In 2014 the European Thyroid Association Executive Committee, given the controversies regarding the treatment of Endo SHyper, formed a task force to develop clinical practice guidelines based on the principles of evidence-based medicine. The task force recognized that recent meta-analyses, including those based on large prospective cohort studies, indicate that SHyper is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures and excess mortality in patients with serum TSH levels <0.1 mIU/l (grade 2 SHyper). Therefore, despite the absence of randomized prospective trials, there is evidence that treatment is indicated in patients older than 65 years with grade 2 SHyper to potentially avoid these serious cardiovascular events, fractures and the risk of progression to overt hyperthyroidism. Treatment could be considered in patients older than 65 years with TSH levels 0.1-0.39 mIU/l (grade 1 SHyper) because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with grade 2 SHyper because of the risk of progression, especially in the presence of symptoms and/or underlying risk factors or co morbidity. Finally, the task force concluded that there are no data to support treating SHyper in younger asymptomatic patients with grade 1 SHyper. These patients should be followed without treatment due to the low risk of progression to overt hyperthyroidism and the weaker evidence for adverse health outcomes. PMID- 26558234 TI - Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark: Following Guidelines or Following Trends? AB - BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experimental with no evidence of superior effect on persistent symptoms according to meta analyses. However, some randomized controlled trials have demonstrated patients' preference for T4/T3 combination therapy as compared to L-T4 monotherapy. In 2013, attention to combination therapy increased in Denmark after a patient published a book describing her experiences with hypothyroidism and treatment. OBJECTIVE: To investigate current Danish trends in the use of T4/T3 combination therapy. METHODS: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further, information was obtained from the Division of Pharmacies and Reimbursement at the Danish Health and Medicines Authority and from the only pharmacy in Denmark producing desiccated thyroid and L-T3 tablets. RESULTS: A total of 384 patients answered the questionnaire, and 293 responders were included. Sixty-nine percent of the responders had six or more symptoms, and 84% reported a treatment effect. Forty-four percent of the responders received their prescriptions from general practitioners; 50% received desiccated thyroid and 28% reported that they adjust their dose themselves. Responders followed by general practitioners more frequently received desiccated thyroid and adjusted their dose themselves. CONCLUSIONS: Increased media focus has changed the prescription pattern of thyroid hormones; European guidelines on T4/T3 combination therapy are not always followed in Denmark and many patients adjust their medication themselves and may therefore be at risk of overtreatment. PMID- 26558235 TI - Metformin Is Associated with a Favorable Outcome in Diabetic Patients with Cervical Lymph Node Metastasis of Differentiated Thyroid Cancer. AB - BACKGROUND AND OBJECTIVE: Type 2 diabetes is known to increase the risk and progression of certain types of cancer. Metformin treatment of diabetic patients is reported to have beneficial effects on some cancers. We evaluated the clinical outcome of diabetic patients with differentiated thyroid cancer (DTC) according to metformin treatment. METHODS: We reviewed 943 patients diagnosed with DTC after total thyroidectomy between 1995 and 2005 in a tertiary hospital. The study involved 60 diabetic patients and 210 control patients matched for age, sex, body mass index (BMI), and tumor size. RESULTS: There were no differences in the clinicopathological features and disease-free survival (DFS) between diabetic patients and the control group over 8.9 years of follow-up. Of the diabetic patients with DTC, 35 patients (58%) were treated with metformin. There were no differences in age, sex, BMI, tumor size, antidiabetic medication, glycated hemoglobin, or C-peptide levels in metformin and nonmetformin groups. However, cervical lymph node (LN) metastasis was more prevalent in the metformin group than in the nonmetformin group (OR 3.52, p = 0.035). Among diabetic patients with cervical LN metastasis of DTC, the metformin subgroup (17.1 years) was associated with longer DFS than the nonmetformin subgroup (8.6 years) (HR 0.16, p = 0.021); metformin treatment was also associated with longer DFS in this subgroup in multivariate analysis after adjusting age, BMI, duration of diabetes, presence of tumor at resection margin, and serum thyroglobulin level at ablation (HR 0.03, p = 0.035). CONCLUSIONS: Metformin treatment is associated with low recurrence in diabetic patients with cervical LN metastasis of DTC. PMID- 26558236 TI - Role of Core Needle Biopsy in the Management of Atypia/Follicular Lesion of Undetermined Significance Thyroid Nodules: Comparison with Repeat Fine-Needle Aspiration in Subcategory Nodules. AB - BACKGROUND: The role of repeat fine-needle aspiration (RFNA) or core needle biopsy (CNB) has not been established in nodules categorized as atypia/follicular lesion of undetermined significance (AUS/FLUS). OBJECTIVE: The purpose of this study was to retrospectively determine whether CNB is more useful for management decisions than RFNA at each subcategory of AUS/FLUS nodules. METHODS: This study included 158 AUS/FLUS nodules (>=1 cm) from 153 consecutive patients who underwent both RFNA and CNB. The AUS/FLUS nodules were subcategorized into nuclear atypia (NA) and follicular lesions with other atypia (FOA). The diagnostic results and rate of determined management by RFNA and CNB were compared at each subcategory. The diagnostic values of RFNA and CNB for malignancy were evaluated in nodules with final diagnoses. RESULTS: CNB showed a lower rate of AUS/FLUS diagnosis, higher rates of benign and follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN) diagnoses (p <= 0.038), and marginally higher rates of malignant diagnosis than RFNA in the NA subcategory. CNB showed a higher rate of FN/SFN (p = 0.007) than RFNA in the FOA subcategory. CNB also demonstrated a higher rate of surgery decision than RFNA in both the NA subcategory (20.2 vs. 9.6%, p < 0.001) and FOA subcategory (20.8 vs. 5.6%, p = 0.007), and a higher rate of observation decision only in the NA subcategory (48.1 vs. 35.6%, p = 0.035). CNB demonstrated a higher diagnostic performance for malignancy overall in the nodules compared with RFNA. CONCLUSION: CNB may be more useful for management decisions than RFNA in both the NA and FOA subcategories, and has the potential to be a first-line alternative diagnostic tool in initially diagnosed AUS/FLUS nodules. PMID- 26558237 TI - Presence of Thyroid-Stimulating Hormone Receptor Antibodies in a Patient with Subacute Thyroiditis followed by Hypothyroidism and Later Graves' Disease with Ophthalmopathy: A Case Report. AB - BACKGROUND: The development of Graves' disease (GD) after subacute thyroiditis (SAT) is very rare and only a limited number of cases have been reported. OBJECTIVES: Here, we report a patient with SAT followed by hypothyroidism and later GD, with ophthalmopathy, occurring 11 years after SAT. CONCLUSION: This case illustrates the appearance of thyroid-stimulating hormone (TSH) receptor antibodies in a female 1 year after SAT, the development of hypothyroidism requiring thyroxine, and later the occurrence of GD with severe ophthalmopathy, 11 years after SAT. The occurrence of SAT and GD may be coincidental but SAT may have induced the appearance of TSH-receptor antibodies, with the bioactivity changing from blocking, leading to hypothyroidism, and later to a stimulating activity that led to GD in a genetically susceptible patient. PMID- 26558238 TI - Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease. AB - BACKGROUND: Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. OBJECTIVE: Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. METHODS: Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-MUg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses <=15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. RESULTS: Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. CONCLUSION: When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI. PMID- 26558239 TI - Unusual Manifestation of Graves' Disease: Ventricular Fibrillation. AB - BACKGROUND: It is well known that thyrotoxicosis causes rhythm disorders including sinus tachycardia, atrial fibrillation, and atrial flutter. Atrial fibrillation is the most common arrhythmia in thyrotoxicosis, occurring in 5-15% of patients over 60 years of age, whereas ventricular arrhythmia is an unusual manifestation. CASE REPORT: An 18-year-old Japanese woman was admitted to our emergency department because of loss of consciousness caused by ventricular fibrillation. She had been diagnosed with Graves' disease only 5 days earlier and had no other past medical history. Blood examination showed no obvious abnormality except thyrotoxicosis, and coronary angiography revealed patent coronary arteries. She was diagnosed with thyroid storm due to Graves' disease and is currently healthy during outpatient follow-up. CONCLUSION: This case highlights that thyrotoxicosis can, albeit extremely rarely, cause ventricular fibrillation even in the absence of hypokalemia or underlying cardiovascular disease. PMID- 26558240 TI - The pedagogical value of autopsy. PMID- 26558241 TI - Chronic Chagas cardiomyopathy. PMID- 26558242 TI - Lemierre's syndrome due to intratumoral abscess of the uvula. AB - Lemierre's syndrome (LS), described in detail in 1936, used to be a life threatening entity until the advent of antibiotics. Tonsillitis or pharyngitis are the main primary infections and oropharyngeal anaerobic flora is the predominant etiology. However, other primary site infections, as well as other microbiological agents have been reported since the first description. Inflammatory symptoms in the neck and marked findings on physical examination predominate the majority of cases. Nonetheless, the authors report the case of a 54-year-old man with a history of dysphagia followed by cough, purulent expectoration, and fever. The bad condition of his dentition was noteworthy. During the diagnostic work-up, an ulcerated lesion in the uvula and a middle lobe pneumonia were disclosed. Streptococcus viridans was isolated from blood culture. On the fifth day of hospitalization, the patient died after a copious episode of hemoptysis. The autopsy findings depicted an abscess within a squamous cell carcinoma of the uvula, pharyngitis with carotid sheath spreading accompanied by pylephlebitis and thrombosis of the internal jugular vein up to the innominate vein, surrounded by an abscess in the mediastinum. Alveolar hemorrhage and pneumonia were also present. We conclude that the ulcerated carcinoma of the uvula housed an abscess, facilitated by the poor oral hygiene, which triggered LS and the descending mediastinitis. Pulmonary involvement was due to the septic embolism from the internal jugular vein. We would like to highlight the uvula abscess as the primary site of infection in this case of LS with S. viridans as the causative agent. PMID- 26558243 TI - Congenital cystic adenomatoid malformation type I. AB - Congenital cystic adenomatoid malformation (CCAM) is an hamartomatous congenital pulmonary airway malformation with incidence ranging between 1:10,000 and 1:35,000 newborns. Currently CCAM is classified into five groups according to clinical and pathological features. The clinical outcome varies depending on the subtype and the extent of involvement. The authors report the case of a premature male newborn with the prenatal diagnosis of CCAM Type 1 associated with cardiac right axis deviation, who died 67 hours after birth due to respiratory failure. In addition to the autopsy report of this rare entity, the authors present its classification and prognosis. PMID- 26558244 TI - Membranous nephropathy PLA2R+ associated with Chagas disease. AB - Chagas disease (CD) - a tropical parasitic disease caused by the protozoan Trypanosoma cruzi - is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure. PMID- 26558245 TI - Dengue fever as a cause of hemophagocytic lymphohistiocytosis. AB - Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, providing suitable conditions for Aedes aegypti breeding and survival. In Brazil for instance it is from January to June. Dengue may cause marked changes in bone marrow that result in hypocellularity and, consequently, thrombocytopenia and leucopenia, along with an increase in hematocrit, which is secondary to capillary leakage. However, those abnormalities are usually self limited, and do not warrant further investigations, such as a marrow biopsy or a myelogram. The occurrence of persistent reactive hemophagocytosis is uncommon and usually leads to serious adverse outcomes. The authors report the case of an 8 year old girl complaining of high-grade fever, malaise, headache, abdominal pain and a cutaneous rash. Laboratory examination revealed atypical lymphocytosis on peripheral blood count, hyperbilirrunemia, abnormal liver enzymes and clotting tests. Serology was positive for dengue. Because of the persistence of fever and laboratory examinations were consistent with hemophagocytic lymphohistiocytosis (HLH) a bone marrow aspiration was performed, which confirmed the presence of hemophagocytosis. Hence we report a rare presentation of dengue accompanied by self-limited HLH that hopefully evolve to favorable outcome. PMID- 26558246 TI - Acute Hemorrhagic Edema of Infancy: an unusual diagnosis for the general pediatrician. AB - Acute Hemorrhagic Edema of Infancy (AHEI) is a rare leukocytoclastic vasculitis, clinically characterized by the classical triad: palpable purpuric skin lesions, edema and fever, and is commonly misdiagnosed as Henoch-Schonlein purpura. In addition to its sudden onset, AHEI is also characterized by its self-limited course with complete and spontaneous recovery occurring between 1 and 3 weeks. Because of the scarcity of studies on therapy with corticosteroids, the conservative approach is usually recommended. The authors report an unusual case of an one-year-old boy who presented with typical cutaneous rash of AHEI and orchitis, the latter showing complete resolution after less than 24 hours of prednisolone therapy. The authors call attention to this entity mainly as a differential diagnosis of Henoch-Schonlein purpura and to the importance of new studies to establish the benefits of corticosteroid therapy for AHEI. PMID- 26558247 TI - Atypical behavioral and psychiatric symptoms: Neurosyphilis should always be considered. AB - Syphilis still remains a major health concern worldwide because of the possibility of serious medical and psychological consequences, long-term disability, and death. Neurosyphilis (NS) may occur at any stage of infection. Its clinical presentation has been changing over recent years including- psychiatric and neurocognitive symptoms. Several recent studies have described cases with these symptoms as the principal signs of NS. We present the case of neurosyphilis with a psychiatric presentation characterized by mood disturbance and auditory and visual hallucinations. PMID- 26558248 TI - Gastric metastasis as the first manifestation of an invasive lobular carcinoma of the breast. AB - Gastrointestinal metastases from breast cancer are rare and generally occur several years after the diagnosis of the primary lesion. The diagnosis of gastric metastasis as the initial presentation of breast cancer is even rarer and can potentially mimic gastric carcinoma. We report the case of a 66-year-old female patient submitted to a total gastrectomy because of the histological diagnosis of undifferentiated gastric carcinoma. During the surgical procedure, biopsies of the peritoneum and the liver were performed, which were consistent with metastatic breast invasive lobular carcinoma (ILC). The primary lesion of the breast was detected during the post-operative period, when a 4-cm-long lesion was detected on physical examination and mammography. The revision of the gastric biopsy confirmed the diagnosis of ILC. The authors call attention to the rarity of gastrointestinal metastases as the initial presentation of breast ILC. PMID- 26558250 TI - Erratum: missing competing interests in editorial. AB - [This corrects the article DOI: 10.4322/acr.2015.010.]. PMID- 26558249 TI - Bilateral mandibular osteomyelitis mimicking periapical cysts in a patient with sickle cell anemia. AB - Sickle cell anemia (SCA) is a hemoglobin disorder that occurs more commonly among Afro-descendants. The authors report the case of a 28-year-old Afro-descendent male patient with the diagnosis of homozygotic sickle cell disease (SCD) referred for evaluation of mandibular lesions. The patient's main complaints included pain and bilateral teeth mobility. An intraoral examination revealed gingiva recession affecting the lower molars with extensive root exposure. A panoramic x-ray showed two radiolucent symmetrical periapical lesions evolving both the first and the second lower molars, bilaterally. The diagnostic hypotheses comprised odontogenic infection, among others. Besides antimicrobial therapy, the two molars of both sides were extracted and bone was collected for histopathological and microbiological analyses. Osteomyelitis was diagnosed, and Streptococcus viridans was recovered from the culture media. Mandibular osteomyelitis should be considered as a diagnosis in patients with SCD. The present case offers an alert to clinicians about the importance of knowing jaw lesions related to SCA. PMID- 26558251 TI - Progression of Monoclonal Gammopathy with Undetermined Significance to Multiple Myeloma Diagnosed by Kidney Biopsy: A Case Report. AB - Monoclonal gammopathy with undetermined significance (MGUS) carries a risk of progression to multiple myeloma, and progression is usually diagnosed with changes in M-protein or bone marrow biopsy. We report a case of 62-year-old female patient showing MGUS progression to multiple myeloma without significant changes in M-protein but diagnosed by kidney biopsy. During the follow-ups, azotemia and tubular proteinuria were aggravated without elevation of M-protein. Kidney biopsy showed intratubular and glomerular inclusions associated with plasma cell dysplasia. The progression of MGUS to multiple myeloma was diagnosed by this kidney biopsy. The patient's renal function and tubular proteinuria were markedly improved after chemotherapy. PMID- 26558252 TI - Reversible Ceftriaxone-Induced Pseudolithiasis in an Adult Patient with Maintenance Hemodialysis. AB - Ceftriaxone (CTRX) is a third-generation cephalosporin widely used for the treatment of bacterial infections in patients with renal disease because of its excretion by both renal and hepatic mechanisms. Biliary pseudolithiasis is a known CTRX-associated complication; however, there have been no studies of this adverse event in adult patients receiving maintenance hemodialysis. Here we report the case of a 79-year-old Japanese woman with end-stage renal disease (ESRD) receiving maintenance hemodialysis who developed CTRX-induced pseudolithiasis. The patient received CTRX for bronchial pneumonia. Fifteen days following CTRX initiation, the patient presented with stomachache. Because of the presence of one gallstone and increased gallbladder wall thickness on computed tomography scans, not detected at the onset of pneumonia, the patient was diagnosed with CTRX-induced gallbladder pseudolithiasis. CTRX was discontinued immediately. At 48 days following CTRX withdrawal, the gallstone and thickening of the gallbladder wall had completely resolved. ESRD may be a risk factor for CTRX-induced pseudolithiasis as hepatic excretion of CTRX is the predominant clearance mechanism in patients with ESRD. More attention should be paid to CTRX induced pseudolithiasis following the use of CTRX in ESRD patients. PMID- 26558254 TI - Evaluating the Cassandra NoSQL Database Approach for Genomic Data Persistency. AB - Rapid advances in high-throughput sequencing techniques have created interesting computational challenges in bioinformatics. One of them refers to management of massive amounts of data generated by automatic sequencers. We need to deal with the persistency of genomic data, particularly storing and analyzing these large scale processed data. To find an alternative to the frequently considered relational database model becomes a compelling task. Other data models may be more effective when dealing with a very large amount of nonconventional data, especially for writing and retrieving operations. In this paper, we discuss the Cassandra NoSQL database approach for storing genomic data. We perform an analysis of persistency and I/O operations with real data, using the Cassandra database system. We also compare the results obtained with a classical relational database system and another NoSQL database approach, MongoDB. PMID- 26558253 TI - Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura. AB - Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients. PMID- 26558255 TI - RECORD: Reference-Assisted Genome Assembly for Closely Related Genomes. AB - Background. Next-generation sequencing technologies are now producing multiple times the genome size in total reads from a single experiment. This is enough information to reconstruct at least some of the differences between the individual genome studied in the experiment and the reference genome of the species. However, in most typical protocols, this information is disregarded and the reference genome is used. Results. We provide a new approach that allows researchers to reconstruct genomes very closely related to the reference genome (e.g., mutants of the same species) directly from the reads used in the experiment. Our approach applies de novo assembly software to experimental reads and so-called pseudoreads and uses the resulting contigs to generate a modified reference sequence. In this way, it can very quickly, and at no additional sequencing cost, generate new, modified reference sequence that is closer to the actual sequenced genome and has a full coverage. In this paper, we describe our approach and test its implementation called RECORD. We evaluate RECORD on both simulated and real data. We made our software publicly available on sourceforge. Conclusion. Our tests show that on closely related sequences RECORD outperforms more general assisted-assembly software. PMID- 26558256 TI - A Clinical Picture of the Visual Outcome in Adamantiades-Behcet's Disease. AB - Adamantiades-Behcet's disease is a multisystemic vasculitis with multiorgan involvement. Ocular disorders occur often in this syndrome typically in the form of a relapsing-remitting panuveitis and vasculitis and can lead to blindness as one of its most disabling complications if left untreated. There are known risk factors related with the worst visual prognosis, which require early and intensive treatment in order to obtain a rapid suppression of inflammation and to prevent future relapses. The management strategy to avoid vision loss and blindness currently involves the use of local and systemic drugs including steroids and immunosuppressive and biologic agents. This review aims to demonstrate how the introduction and the use of biologic agents improves the visual outcome of patients with Adamantiades-Behcet's disease. PMID- 26558257 TI - Identification and Analysis of the SET-Domain Family in Silkworm, Bombyx mori. AB - As an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. SET-domain-containing proteins belong to a group of enzymes named after a common domain that utilizes the cofactor S-adenosyl-L-methionine (SAM) to achieve methylation of its substrates. Many SET-domain-containing proteins have been shown to display catalytic activity towards particular lysine residues on histones, but emerging evidence also indicates that various nonhistone proteins are specifically targeted by this clade of enzymes. To explore their diverse functions of SET-domain superfamily in insect, we identified, cloned, and analyzed the SET-domains proteins in silkworm, Bombyx mori. Firstly, 24 genes containing SET domain from silkworm genome were characterized and 17 of them belonged to six subfamilies of SUV39, SET1, SET2, SUV4-20, EZ, and SMYD. Secondly, SET domains of silkworm SET-domain family were intraspecifically and interspecifically conserved, especially for the catalytic core "NHSC" motif, substrate binding site, and catalytic site in the SET domain. Lastly, further analyses indicated that silkworm SET-domain gene BmSu(var)3-9 owned different characterization and expression profiles compared to other invertebrates. Overall, our results provide a new insight into the functional and evolutionary features of SET-domain family. PMID- 26558258 TI - Role and Function of MicroRNAs in Extracellular Vesicles in Cardiovascular Biology. AB - Intercellular communication mediated by extracellular vesicles is crucial for preserving vascular integrity and in the development of cardiovascular disease. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes that can be found in almost every fluid compartment of the body like blood, saliva, and urine. In the recent years, a lot of reports came up suggesting that major cardiovascular and metabolic pathologies like atherogenesis, heart failure, or diabetes are highly influenced by transfer of microRNAs via extracellular vesicles leading to altered protein expression and phenotypes of recipient cells. The following review will summarize the fast developing field of intercellular signaling in cardiovascular biology by microRNA-containing extracellular vesicles. PMID- 26558259 TI - Different Persistence of the Cellular Effects Promoted by Protein Kinase CK2 Inhibitors CX-4945 and TDB. AB - We compare the cellular efficacy of two selective and cell permeable inhibitors of the antiapoptotic kinase CK2. One inhibitor, CX-4945, is already in clinical trials as antitumor drug, while the other, TDB, has been recently successfully employed to demonstrate the implication of CK2 in cellular (dis)regulation. We found that, upon treatment of cancer cells with these compounds, the extent of inhibition of endocellular CK2 is initially comparable but becomes significantly different after the inhibitors are removed from the cellular medium: while in CX 4945 treated cells CK2 activity is restored to control level after 24 h, in the case of TDB it is still strongly reduced after 4 days from removal. The biological effects of the two inhibitors have been analyzed by performing clonogenic, spheroid formation, and wound-healing assays: we observed a permanent inhibition of cell survival and migration in TDB-treated cells even after the inhibitor removal, while in the case of CX-4945 only its maintenance for the whole duration of the assay insured a persisting effect. We suggest that the superiority of TDB in maintaining kinase activity inhibited and perpetuating the consequent effects is an added value to be considered when planning new therapies based on CK2 targeting. PMID- 26558260 TI - The Clinical Characteristics and Treatment of Cerebral Microarteriovenous Malformation Presenting with Intracerebral Hemorrhage: A Series of 13 Cases. AB - OBJECT: The aim of this report was to explore the clinical presentation, radiological features, treatment methods, and outcome of micro-AVMs presenting with intracerebral hemorrhage. METHODS: The clinical data, radiological features, treatment, and follow-up results for a consecutive series of 13 cases with micro AVMs were retrospectively analyzed. RESULTS: All 13 patients presented with intracerebral hemorrhage. Ten cases were confirmed by enhanced thin layer CT scanning and CTA, and the other 3 cases were confirmed by DSA. Treatment consisted of surgical removal in 10 cases, endovascular embolization in 1, and radiosurgery in 2. The modified GOS score was achieved in the third month after discharge: 10 cases were rated with 5 points (good recovery), 1 case was rated with 4 points (mild disability), and 2 cases were rated with 3 points (severe disability). During follow-up, No case of rebleeding was reported. CONCLUSIONS: Intracerebral hemorrhage is the main clinical manifestation of micro-AVMs. It is beneficial to find a tiny nidus of dense vessels located on hematoma wall on enhanced thin layer CT scanning for a clear diagnosis and to detect any abnormal feeding artery or venous drainage for an indirect diagnostic evidence. Resection is the main method of treatment for micro-AVMs. PMID- 26558261 TI - Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest. AB - OBJECTIVE: In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). METHODS: Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. RESULTS: There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. CONCLUSION: Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID- 26558262 TI - Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review. AB - PURPOSE: This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. METHODS: The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. PATHOPHYSIOLOGY AND TREATMENT: FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. CONCLUSION: The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein. PMID- 26558264 TI - Corrigendum to "Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing". PMID- 26558263 TI - Ocular Blood Flow and Normal Tension Glaucoma. AB - Normal tension glaucoma (NTG) is known as a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, even though the intraocular pressure (IOP) does not exceed the normal range. The pathophysiology of NTG remains largely undetermined. It is hypothesized that the abnormal ocular blood flow is involved in the pathogenesis of this disease. A number of evidences suggested that the vascular factors played a significant role in the development of NTG. In recent years, the new imaging techniques, fluorescein angiography, color Doppler imaging (CDI), magnetic resonance imaging (MRI), and laser speckle flowgraphy (LSFG), have been used to evaluate the ocular blood flow and blood vessels, and the impaired vascular autoregulation was found in patients with NTG. Previous studies showed that NTG was associated with a variety of systemic diseases, including migraine, Alzheimer's disease, primary vascular dysregulation, and Flammer syndrome. The vascular factors were involved in these diseases. The mechanisms underlying the abnormal ocular blood flow in NTG are still not clear, but the risk factors for glaucomatous optic neuropathy likely included oxidative stress, vasospasm, and endothelial dysfunction. PMID- 26558265 TI - Ocular Blood Flow and Visual Function. PMID- 26558266 TI - In Vitro Behavior of Human Adipose Tissue-Derived Stem Cells on Poly(epsilon caprolactone) Film for Bone Tissue Engineering Applications. AB - Bone tissue engineering is an emerging field, representing one of the most exciting challenges for scientists and clinicians. The possibility of combining mesenchymal stem cells and scaffolds to create engineered tissues has brought attention to a large variety of biomaterials in combination with osteoprogenitor cells able to promote and regenerate bone tissue. Human adipose tissue is officially recognized as an easily accessible source of mesenchymal stem cells (AMSCs), a significant factor for use in tissue regenerative medicine. In this study, we analyze the behavior of a clonal finite cell line derived from human adipose tissue seeded on poly(epsilon-caprolactone) (PCL) film, prepared by solvent casting. PCL polymer is chosen for its good biocompatibility, biodegradability, and mechanical properties. We observe that AMSCs are able to adhere to the biomaterial and remain viable for the entire experimental period. Moreover, we show that the proliferation process and osteogenic activity of AMSCs are maintained on the biofilm, demonstrating that the selected biomaterial ensures cell colonization and the development of an extracellular mineralized matrix. The results of this study highlight that AMSCs and PCL film can be used as a suitable model to support regeneration of new bone for future tissue engineering strategies. PMID- 26558267 TI - 3D Surface Profile and Color Stability of Tooth Colored Filling Materials after Bleaching. AB - This study aims to evaluate the effects of vital tooth bleaching with carbamide peroxide home bleaching and in-office bleaching on the color stability and 3D surface profile of dental restorative filling materials. Thirty discs (n = 30) measure 6 mm in diameter and 2 mm thick for each of three restorative materials. These are nanofilled composite Filtek Z350 XT, the submicron composite Estelite Sigma Quick, and nanofilled glass ionomer Ketac N100 nanoionomer and were fabricated in shade A2. Each group was further divided into three subgroups (n = 10): subgroup A (Opalescence PF), subgroup B (Opalescence Boost in-office bleaching), and subgroup C (distilled water) serving as control. Samples were bleached according to the manufacturer's instructions for a period of two weeks. The Commission Internationale de L'Eclairage (CIE L(*), a(*), b(*)) system was chosen for image processing, while 3D surface profile was tested with atomic force microscopy (AFM). Statistical analyses were performed with the Mann-Whitney tests and Krusal-Wallis with a P value of <= 0.05. The three restorative materials showed significant color changes (DeltaE); P <= 0.05. In diminishing order, the mean color changes recorded were Estelite Sigma (3.82 +/- 1.6) > Ketac Nano (2.97 +/- 1.2) > Filtek Z350 XT (2.25 +/- 1.0). However, none of the tested materials showed statistically significant changes in surface roughness; P > 0.05. PMID- 26558268 TI - Atrial Fibrillation and Coronary Artery Disease as Risk Factors of Retinal Artery Occlusion: A Nationwide Population-Based Study. AB - We use Taiwanese national health insurance research database (NHIRD) to investigate whether thrombolism (carotid artery disease (CAD) as a surrogate) or embolism (atrial fibrillation (AF) as a surrogate) plays roles in later retinal artery occlusion (RAO) development and examine their relative weights. The relative risks of RAO between AF and CAD patients and controls were compared by estimating the crude hazard ratio with logistic regression. Kaplan-Meier analysis was used to calculate the cumulative incidence rates of developing RAO, and a log rank test was used to analyze the differences between the survival curves. Separate Cox proportional hazard regressions were done to compute the RAO-free rate after adjusting for possible confounding factors such as age and sex. The crude hazard ratios were 7.98 for the AF group and 5.27 for the CAD group, and the adjusted hazard ratios were 8.32 and 5.34 for the AF and CAD groups, respectively. The observation time with RAO-free was shorter for AF compared with CAD group (1490 versus 1819 days). AF and CAD were both risk factors for RAO with different hazard ratios. To tackle both AF and CAD is crucial for curbing RAO. PMID- 26558269 TI - Trying to Put the Puzzle Together: Age and Performance Level Modulate the Neural Response to Increasing Task Load within Left Rostral Prefrontal Cortex. AB - Age-related working memory decline is associated with functional cerebral changes within prefrontal cortex (PFC). Kind and meaning of these changes are heavily discussed since they depend on performance level and task load. Hence, we investigated the effects of age, performance level, and load on spatial working memory retrieval-related brain activation in different subregions of the PFC. 19 younger (Y) and 21 older (O) adults who were further subdivided into high performers (HP) and low performers (LP) performed a modified version of the Corsi Block-Tapping test during fMRI. Brain data was analyzed by a 4 (groups: YHP, OHP, YLP, and OLP) * 3 (load levels: loads 4, 5, and 6) ANOVA. Results revealed significant group * load interaction effects within rostral dorsolateral and ventrolateral PFC. YHP showed a flexible neural upregulation with increasing load, whereas YLP reached a resource ceiling at a moderate load level. OHP showed a similar (though less intense) pattern as YHP and may have compensated age effects at high task load. OLP showed neural inefficiency at low and no upregulation at higher load. Our findings highlight the relevance of age and performance level for load-dependent activation within rostral PFC. Results are discussed in the context of the compensation-related utilization of neural circuits hypothesis (CRUNCH) and functional PFC organization. PMID- 26558270 TI - Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease. AB - BACKGROUND: We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. METHODS: A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. RESULTS: Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. CONCLUSION: IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs. PMID- 26558272 TI - Targeting Cellular Metabolism Chemosensitizes the Doxorubicin-Resistant Human Breast Adenocarcinoma Cells. AB - Metabolic energy preferentially produced by glycolysis was an advantageous metabolic phenotype of cancer cells. It is also an essential contributor to the progression of multidrug resistance in cancer cells. By developing human breast cancer MCF-7 cells resistant to doxorubicin (DOX) (MCF-7/MDR cells), the effects and mechanisms of 2-deoxy-D-glucose (2DG), a glucose analogue, on reversing multidrug resistance were investigated. 2DG significantly inhibited the viability of MCF-7/MDR cells and enhanced DOX-induced apoptosis by upregulating protein expression of AMPKalpha, P53, and caspase-3. The study demonstrated that energy restriction induced by 2DG was relevant to the synergistic effect of 2DG and DOX. The proteins of multidrug gene (the MDR-related protein, MRP1) and P-glycoprotein (P-gp) in MCF-7/MDR cells were downregulated after exposure to 2DG, accompanied with the suppression of the activity of ATP-dependent drug-efflux pump and transmembrane transporter, increasing the intracellular accumulation of DOX to reverse the chemoresistance in multidrug cancer cells. PMID- 26558273 TI - The Impact of Pain Assessment on Critically Ill Patients' Outcomes: A Systematic Review. AB - In critically ill patients, pain is a major problem. Efficient pain management depends on a systematic, comprehensive assessment of pain. We aimed to review and synthesize current evidence on the impact of a systematic approach to pain assessment on critically ill patients' outcomes. A systematic review of published studies (CINAHL, PUBMED, SCOPUS, EMBASE, and COCHRANE databases) with predetermined eligibility criteria was undertaken. Methodological quality was assessed by the EPHPP quality assessment tool. A total of 10 eligible studies were identified. Due to big heterogeneity, quantitative synthesis was not feasible. Most studies indicated the frequency, duration of pain assessment, and types of pain assessment tools. Methodological quality assessment yielded "strong" ratings for 5/10 and "weak" ratings for 3/10 studies. Implementation of systematic approaches to pain assessment appears to associate with more frequent documented reports of pain and more efficient decisions for pain management. There was evidence of favorable effects on pain intensity, duration of mechanical ventilation, length of ICU stay, mortality, adverse events, and complications. This systematic review demonstrates a link between systematic pain assessment and outcome in critical illness. However, the current level of evidence is insufficient to draw firm conclusions. More high quality randomized clinical studies are needed. PMID- 26558271 TI - Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration. AB - The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins' main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such as alpha5, alphaV, beta1, and beta3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis. PMID- 26558274 TI - 1,213 Cases of Treatment of Facial Acne Using Indocyanine Green and Intense Pulsed Light in Asian Skin. AB - BACKGROUND: Photodynamic therapy (PDT) has been used for acne, with various combinations of photosensitizers and light sources. OBJECTIVE: We evaluated the effectiveness and safety of indocyanine green (ICG) and intense pulsed light (IPL) in the treatment of acne. MATERIALS AND METHODS: A total of 1,213 patients with facial acne were retrospectively reviewed. Patients received three or five treatments of ICG and IPL at two-week intervals. Clinical response to treatment was assessed by comparing pre- and posttreatment clinical photographs and patient satisfaction scores. RESULTS: Marked to excellent improvement was noted in 483 of 1,213 (39.8%) patients, while minimal to moderate improvement was achieved in the remaining 730 (60.2%) patients. Patient satisfaction scores revealed that 197 (16.3%) of 1,213 patients were highly satisfied, 887 (73.1%) were somewhat satisfied, and 129 (10.6%) were unsatisfied. There were no significant side effects. CONCLUSION: These results suggest that PDT with ICG and IPL can be effectively and safely used in the treatment of acne. PMID- 26558275 TI - No Evidence for Retinal Damage Evolving from Reduced Retinal Blood Flow in Carotid Artery Disease. AB - INTRODUCTION: Carotid artery disease (CAD) comprising high-grade internal carotid artery stenosis (CAS) or carotid artery occlusion (CAO) may lead to ipsilateral impaired cerebral blood flow and reduced retinal blood supply. OBJECTIVE: To examine the influence of chronic CAD on retinal blood flow, retinal morphology, and visual function. METHODS: Patients with unilateral CAS >= 50% (ECST criteria) or CAO were grouped according to the grade of the stenosis and to the flow direction of the ophthalmic artery (OA). Retinal perfusion was measured by transorbital duplex ultrasound, assessing central retinal artery (CRA) blood flow velocities. In addition, optic nerve and optic nerve sheath diameter were measured. Optical coherence tomography (OCT) was performed to study retinal morphology. Visual function was assessed using high- and low-contrast visual paradigms. RESULTS: Twenty-seven patients were enrolled. Eyes with CAS >= 80%/CAO and retrograde OA blood flow showed a significant reduction in CRA peak systolic velocity (no-CAD side: 0.130 +/- 0.035 m/s, CAS/CAO side: 0.098 +/- 0.028; p = 0.005; n = 12). OCT, optic nerve thicknesses, and visual functional parameters did not show a significant difference. CONCLUSION: Despite assessable hemodynamic effects, chronic high-grade CAD does not lead to gaugeable morphological or functional changes of the retina. PMID- 26558276 TI - The Relationship of On-Call Work with Fatigue, Work-Home Interference, and Perceived Performance Difficulties. AB - OBJECTIVES: This study examined the relationship between on-call duty exposure (active and total on-call hours a month, number of calls per duty) and employees' experiences of being on-call (stress due to unpredictability, ability to relax during inactive on-call periods, restrictions during on-call duties, on-call work demands, and satisfaction with compensation for on-call duties) on the one hand and fatigue, strain-based and time-based work-home interference (WHI), and perceived on-call performance difficulties (PPD) on the other hand. METHODS: Cross-sectional survey data were collected among a large heterogeneous sample of Dutch employees (N = 5437). The final sample consisted of 157 on-call workers (23 69 years, 71% males). Data were analyzed by means of hierarchical regression analyses (controlling for age and job characteristics). RESULTS: Differences in on-call work exposure were not systematically related to fatigue, WHI, and PPD (all p's >0.50). The experience of being on-call explained a medium proportion of the variation in fatigue and strain-based WHI and a medium to large proportion of the variation in time-based WHI and PPD over and above the control variables. CONCLUSIONS: Our results suggest that it is employees' experience of being on call, especially the experience of stress due to the unpredictability, rather than the amount of exposure, that is related to fatigue, WHI, and perceived on call performance difficulties. PMID- 26558277 TI - Auditing of Monitoring and Respiratory Support Equipment in a Level III-C Neonatal Intensive Care Unit. AB - BACKGROUND: Random safety audits (RSAs) are a safety tool but have not been widely used in hospitals. OBJECTIVES: To determine the frequency of proper use of equipment safety mechanisms in relation to monitoring and mechanical ventilation by performing RSAs. The study also determined whether factors related to the patient, time period, or characteristics of the area of admission influenced how the device safety systems were used. METHODS: A prospective observational study was conducted in a level III-C Neonatal Intensive Care Unit (NICU) during 2012. 87 days were randomly selected. Appropriate overall use was defined when all evaluated variables were correctly programmed in the audited device. RESULTS: A total of 383 monitor and ventilator audits were performed. The Kappa coefficient of interobserver agreement was 0.93. The rate of appropriate overall use of the monitors and respiratory support equipment was 33.68%. Significant differences were found with improved usage during weekends, OR 1.85 (1.12-3.06, p = 0.01), and during the late shift (3 pm to 10 pm), OR 1.59 (1.03-2.4, p = 0.03). CONCLUSIONS: Equipment safety systems of monitors and ventilators are not properly used. To improve patient safety, we should identify which alarms are really needed and where the difficulties lie for the correct alarm programming. PMID- 26558278 TI - The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation. AB - Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) turned out to be particularly potent (Ki = 0.058 MUM) and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX 4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2alpha) and CK2 holoenzyme (CK2alpha2 beta2), consistent with in silico and in vitro analyses. PMID- 26558279 TI - New Onset Diplopia in Patients with Nasopharyngeal Carcinoma following Concurrent Chemoradiotherapy: Clinical Features and Etiology. AB - PURPOSE: To investigate the clinical features and etiology of nasopharyngeal carcinoma (NPC) patients with new onset diplopia after concurrent chemoradiotherapy. METHODS: We retrospectively reviewed the medical records of NPC patients with new onset diplopia after concurrent chemoradiotherapy from 1998 to 2012 in a cancer center. Their clinical manifestations of ocular motor dysfunction in relation to etiology were investigated. RESULTS: Twenty-three NPC patients with diplopia after concurrent chemoradiotherapy were enrolled in this study. Unilateral cranial VI palsy (91%) was the most common ocular motor dysfunction in these patients. The new onset diplopia in these patients was secondary to tumor recurrence in 12 cases (52%), radiation neuropathy in 8 cases (35%), and skull base osteoradionecrosis in 3 cases (13%). Patients with tumor recurrence and skull base osteoradionecrosis tended to present a rapid progression of the nerve palsy or severe ocular duction deficit. Patients with radiation neuropathy were often manifested by incomplete nerve palsy with insidious onset and slow progression. Patients with osteoradionecrosis were associated with poor prognosis. CONCLUSIONS: A new onset diplopia in NPC patients could be caused by tumor recurrence or treatment complications such as radiation neuropathy and osteoradionecrosis, and they show diverse clinical symptoms, course, and outcome. PMID- 26558280 TI - Current Approach in the Diagnosis and Management of Uveitic Glaucoma. AB - Uveitic glaucoma (UG) typically is associated with very high intraocular pressure (IOP) and more intense optic nerve damage than other glaucoma types. This secondary glaucoma requires an early diagnosis and adequate management of both uveitis and glaucoma. It is mandatory to identify the mechanisms of IOP elevation that in many eyes have multiple combined mechanisms. Management of these patients commonly requires an interdisciplinary approach that includes a glaucoma specialist and rheumatologist to control the inflammation and IOP. Glaucoma surgery is required early in these patients due to the high IOP usually present and is less successful than in primary open-angle glaucoma. Recurrent uveitic episodes, multiple mechanism, and the complications associated with uveitis make surgical management of UG challenging. In this review, the management and treatment of UG are updated to clarify the pathogenesis and prevent optic nerve damage. PMID- 26558281 TI - Analysis of the Oxidative Stress Status in Nonspecific Vaginitis and Its Role in Vaginal Epithelial Cells Apoptosis. AB - Nonspecific vaginitis (NSV), also named bacterial vaginosis, is one of the most common genital system diseases in women during their reproductive years. The specific pathogenic mechanism of NSV is not clear yet. Upon the balance alteration, large amount of reactive oxidant species (ROS) is generated and accumulated in the genital tract, and thus resulting in oxidative stress, which has been reported to be an important trigger of mitochondrial pathway cell apoptosis. In this study, the antioxidant secretion level and antioxidant enzyme activity in the vaginal discharge were evaluated to analyze the oxidative status in the vaginal tract of NSV patients. The effect of oxidative stress on the vaginal mucosa epithelial cell apoptosis was then studied. The role of oxidative stress on NSV development was uncovered; thus open new direction for the prevention and treatment of NSV by providing antiradical agents was revealed. PMID- 26558282 TI - Psychosocial Work Factors and Musculoskeletal Pain: A Cross-Sectional Study among Swedish Flight Baggage Handlers. AB - OBJECTIVE: Flight baggage handlers sort and load luggage to airplanes. This study aimed at investigating associations between psychosocial exposures and low back and shoulder musculoskeletal disorders (MSDs) among Swedish flight baggage handlers. METHODS: A questionnaire addressing MSDs (Standardized Nordic Questionnaire) and psychosocial factors (Copenhagen Psychosocial Questionnaire, COPSOQ) was answered by 525 baggage handlers in six Swedish airports. RESULTS: Low back (LBP) and shoulder pain (SP) were reported by 70% and 60%, respectively. Pain was reported to interfere with work (PIW) by 30% (low back) and 18% (shoulders), and intense pain (PINT) occurred in 34% and 28% of the population. Quality of leadership was the most dissatisfying psychosocial factor, while the most positive was social community at work. Low ratings in the combined domain Work organization and job content were significantly associated with PIW in both low back and shoulders (Adjusted Hazard Ratios 3.65 (95% CI 1.67-7.99) and 2.68 (1.09-6.61)) while lower ratings in the domain Interpersonal relations and leadership were associated with PIW LBP (HR 2.18 (1.06-4.49)) and PINT LBP and SP (HRs 1.95 (1.05-3.65) and 2.11 (1.08-4.12)). CONCLUSION: Severity of pain among flight baggage handlers was associated with psychosocial factors at work, suggesting that they may be a relevant target for intervention in this occupation. PMID- 26558283 TI - The Quantitative Assessment of Imaging Features for the Study of Hirayama Disease Progression. AB - OBJECTIVE: To evaluate the forward shifting of cervical spinal cords in different segments of patients with Hirayama disease to determine whether the disease is self-limiting. METHODS: This study was performed on 11 healthy subjects and 64 patients. According to the duration, the patients were divided into 5 groups (<=1 year, 1-2 years, 2-3 years, 3-4 years, and >= 4 years). Cervical magnetic resonance imaging (MRI) of flexion and conventional position was performed. The distances between the posterior edge of the spinal cord and the cervical spinal canal (X), the anterior and posterior wall of the cervical spinal canal (Y), and the anterior-posterior (A) and the transverse diameter (B) of spinal cord cross sections were measured at different cervical spinal segments (C4 to T1). RESULTS: In cervical flexion position, a significant increase in X/Y of C4-5 segments was found in groups 2-5, the C5-6 and C6-7 segments in groups 1-5, and the C7-T1 segments in group 5 (P < 0.05). The degree of the increased X/Y and cervical flexion X/Y of C5-6 segments were different among the 5 groups (P < 0.05), which was likely due to rapid increases in X/Y during the course of Hirayama's disease. CONCLUSION: The X/Y change progression indicates that Hirayama disease may not be self-limiting. PMID- 26558284 TI - Quercetin Increases Hepatic Homocysteine Remethylation and Transsulfuration in Rats Fed a Methionine-Enriched Diet. AB - This study was aimed at investigating the effects of quercetin on mRNA expression and activity of critical enzymes in homocysteine metabolism in rats fed a methionine-enriched diet. Rats were fed for 6 weeks the following diets, that is, control, 0.5% quercetin, 1.0% methionine, and 1.0% methionine plus 0.5% quercetin diets. Serum homocysteine was significantly increased after methionine treatment and decreased after the addition of quercetin. The mRNA expression of methionine synthase was significantly increased after methionine or methionine plus quercetin supplementation, while its enzymatic activity was significantly increased after methionine plus quercetin supplementation. The mRNA expression and enzymatic activity of cystathionine beta-synthase and cystathionine gamma lyase were upregulated after quercetin, methionine, or quercetin plus methionine treatment and a more significant increase was observed for hepatic cystathionine beta-synthase in the methionine plus quercetin treated rats, suggesting an interaction between methionine and quercetin. Meanwhile, hepatic ratio of S adenosylmethionine to S-adenosylhomocysteine was significantly decreased in response to methionine supplementation and normalized after the addition of quercetin. It is concluded that quercetin reduces serum homocysteine by increasing remethylation and transsulfuration of homocysteine in rats exposed to a methionine-enriched diet. PMID- 26558285 TI - CMP-Neu5Ac Hydroxylase Null Mice as a Model for Studying Metabolic Disorders Caused by the Evolutionary Loss of Neu5Gc in Humans. AB - The purpose of this study was to identify the modification/turnover of gene products that are altered in humans due to evolutionary loss of Neu5Gc. CMP Neu5Ac hydroxylase- (Cmah-) deficient mice show the infiltration of Kupffer cells within liver sinusoids, whereas body and liver weight develop normally. Pathway analysis by use of Illumina MouseRef-8 v2 Expression BeadChip provided evidence that a number of biological pathways, including the glycolysis, gluconeogenesis, TCA cycle, and pentose phosphate pathways, as well as glycogen metabolism-related gene expression, were significantly upregulated in Cmah-null mice. The intracellular glucose supply in Cmah-null mice resulted in mitochondrial dysfunction, oxidative stress, and the advanced glycation end products accumulation that could further induce oxidative stress. Finally, low sirtuin-1 and sirtuin-3 gene expressions due to higher NADH/NAD in Cmah-null mice decreased Foxo-1 and MnSOD gene expression, suggesting that oxidative stress may result in mitochondrial dysfunction in Cmah-null mouse. The present study suggests that mice with CMAH deficiency can be taken as an important model for studying metabolic disorders in humans. PMID- 26558287 TI - Automatic Prosodic Analysis to Identify Mild Dementia. AB - This paper describes an exploratory technique to identify mild dementia by assessing the degree of speech deficits. A total of twenty participants were used for this experiment, ten patients with a diagnosis of mild dementia and ten participants like healthy control. The audio session for each subject was recorded following a methodology developed for the present study. Prosodic features in patients with mild dementia and healthy elderly controls were measured using automatic prosodic analysis on a reading task. A novel method was carried out to gather twelve prosodic features over speech samples. The best classification rate achieved was of 85% accuracy using four prosodic features. The results attained show that the proposed computational speech analysis offers a viable alternative for automatic identification of dementia features in elderly adults. PMID- 26558286 TI - An Integrative Literature Review of Organisational Factors Associated with Admission and Discharge Delays in Critical Care. AB - The literature shows that delayed admission to the intensive care unit (ICU) and discharge delays from the ICU are associated with increased adverse events and higher costs. Identifying factors related to delays will provide information to practice improvements, which contribute to better patient outcomes. The aim of this integrative review was to explore the incidence of patients' admission and discharge delays in critical care and to identify organisational factors associated with these delays. Seven studies were included. The major findings are as follows: (1) explanatory research about discharge delays is scarce and one study on admission delays was found, (2) delays are a common problem mostly due to organisational factors, occurring in 38% of admissions and 22-67% of discharges, and (3) redesigning care processes by improving information management and coordination between units and interdisciplinary teams could reduce discharge delays. In conclusion, patient outcomes can be improved through efficient and safe care processes. More exploratory research is needed to identify factors that contribute to admission and discharge delays to provide evidence for clinical practice improvements. Shortening delays requires an interdisciplinary and multifaceted approach to the whole patient flow process. Conclusions should be made with caution due to the limited number of articles included in this review. PMID- 26558289 TI - An Asynchronous Low Power and High Performance VLSI Architecture for Viterbi Decoder Implemented with Quasi Delay Insensitive Templates. AB - Convolutional codes are comprehensively used as Forward Error Correction (FEC) codes in digital communication systems. For decoding of convolutional codes at the receiver end, Viterbi decoder is often used to have high priority. This decoder meets the demand of high speed and low power. At present, the design of a competent system in Very Large Scale Integration (VLSI) technology requires these VLSI parameters to be finely defined. The proposed asynchronous method focuses on reducing the power consumption of Viterbi decoder for various constraint lengths using asynchronous modules. The asynchronous designs are based on commonly used Quasi Delay Insensitive (QDI) templates, namely, Precharge Half Buffer (PCHB) and Weak Conditioned Half Buffer (WCHB). The functionality of the proposed asynchronous design is simulated and verified using Tanner Spice (TSPICE) in 0.25 um, 65 nm, and 180 nm technologies of Taiwan Semiconductor Manufacture Company (TSMC). The simulation result illustrates that the asynchronous design techniques have 25.21% of power reduction compared to synchronous design and work at a speed of 475 MHz. PMID- 26558288 TI - Transcriptome Analysis of Gelatin Seed Treatment as a Biostimulant of Cucumber Plant Growth. AB - The beneficial effects of gelatin capsule seed treatment on enhanced plant growth and tolerance to abiotic stress have been reported in a number of crops, but the molecular mechanisms underlying such effects are poorly understood. Using mRNA sequencing based approach, transcriptomes of one- and two-week-old cucumber plants from gelatin capsule treated and nontreated seeds were characterized. The gelatin treated plants had greater total leaf area, fresh weight, frozen weight, and nitrogen content. Pairwise comparisons of the RNA-seq data identified 620 differentially expressed genes between treated and control two-week-old plants, consistent with the timing when the growth related measurements also showed the largest differences. Using weighted gene coexpression network analysis, significant coexpression gene network module of 208 of the 620 differentially expressed genes was identified, which included 16 hub genes in the blue module, a NAC transcription factor, a MYB transcription factor, an amino acid transporter, an ammonium transporter, a xenobiotic detoxifier-glutathione S-transferase, and others. Based on the putative functions of these genes, the identification of the significant WGCNA module and the hub genes provided important insights into the molecular mechanisms of gelatin seed treatment as a biostimulant to enhance plant growth. PMID- 26558290 TI - A Push on Job Anxiety for Employees on Managing Recent Difficult to Understand Computing Equipment in the Modern Issues in Indian Banking Quarter. AB - Stress management can be defined as intervention planned to decrease the force of stressors in the administrative center. These can have a human being focus, aimed at raising an individual's ability to cope with stressors and the implementation of the CRM is essential to establish a better performance of the banking sector. Since managing stress and customer relationship management are becoming crucial in the field of management the work has forecasted them in a wide range of dimensions. This paper organizes few preliminary concepts of stress and critically analyzes the CRM strategy implemented by banking sector. Hence the employees of the Banking Industry have been asked to give their opinion about the CRM strategy adopted by banks. In order to provide the background of the employees, the profile of the employees has been discussed initially. The profile of the employees along with their opinion on the CRM practices adopted at Banking Industries has been discussed. In our work progresses we have been taken of two main parameters for consideration and it detriment in which area stress are mainly responds, and also the paper envelopes certain valuable stress management tactics and techniques that are particularly compassionate for people who have been working in the banking sector. Also an attempt to diagnose the impact of underside stress of day to day life in mounting a bigger level stress upon the employees has been made. Further development has been made with a detailed parametric analysis of employee stress conducted with the wide range of key parameters and several rounds of experiments have been conducted with techniques as Kolmogorov-Smirnov test, Garrett ranking, and ANOVA; the work ensures to pave way for an accurate measure in customer handling. The questionnaire is planned to be distributed to 175 employees in the Madurai district banks. PMID- 26558291 TI - Immunosensing of Atrazine with Antibody-Functionalized Cu-MOF Conducting Thin Films. AB - This work reports the assembly of thin films of a silica (SiO2)-modified copper metal organic framework, Cu3(BTC)2 [Cu3(BTC)2@SiO2, BTC = benzene-1,3,5 tricarboxylic acid] on a conducting substrate of NH2-BDC [NH2-BDC = 2 aminobenzene-1,4-dicarboxylic acid] doped polyaniline (PANI). Assembled Cu3(BTC)2@SiO2/BDC-PANI thin films displayed electrical conductivity in the range of 35 MUA. These thin films were conjugated with antiatrazine antibodies to create a novel immunosensing platform. Various structural and spectral characteristics of the synthesized material and its bioconjugate were investigated. The developed immunosensor was used for the conductometric sensing of atrazine. The detection of atrazine was achieved with a high sensor sensitivity (limit of detection = 0.01 nM) and specificity in the presence of diverse pesticides (e.g., endosulfan, parathion, paraoxon, malathion, and monochrotophos). PMID- 26558292 TI - Achievement of Bulky Homochirality in Zeolitic Imidazolate-Related Frameworks. AB - Before this work, adding chiral C centers into zeolitic imidazolate frameworks (ZIFs) has never been realized. Presented here are the first examples on achieving bulky homochirality in ZIF systems, and three homochiral zeolitic imidazolate-related frameworks with sodalite and dia topologies are successfully synthesized by employing enantiopure imidazolate derivatives. The results open a new blueprint on the synthetic design of homochiral ZIFs for future applications. PMID- 26558294 TI - A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of the knee. AB - Methotrexate (MTX) is the first choice disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA) and is referred to as an "anchor drug"; its use has been steadily increasing annually. However, MTX-related lymphoproliferative diseases (MTX-LPDs) have emerged as important complications in the patients with RA. There have been no reports of intra-articular MTX-LPDs of the patients with RA. Atypical cells were found in the patient's joint fluid by cytological examinations, and MTX-LPDs were suspected. The patient discontinued MTX and open synovectomy was performed. The histological findings and immunohistochemical staining of the specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) of MTX-LPDs. After the operation of the patient's left knee joint, pains and swollen joint disappeared with no relapse. The cytological examinations of the synovial fluid followed by knee operation were effective for early diagnosis of MTX-LPD. MTX discontinuation with no chemotherapy followed up with a knee operation improved the recovery of the MTX LPD. PMID- 26558293 TI - Stem cells therapy for ALS. AB - INTRODUCTION: Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS. AREAS COVERED: We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation. EXPERT OPINION: SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory. PMID- 26558295 TI - Marine phospholipids: The current understanding of their oxidation mechanisms and potential uses for food fortification. AB - There is a growing interest in using marine phospholipids (PL) as ingredient for food fortification due to their numerous health benefits. However, the use of marine PL for food fortification is a challenge due to the complex nature of the degradation products that are formed during the handling and storage of marine PL. For example, nonenzymatic browning reactions may occur between lipid oxidation products and primary amine group from phosphatidylethanolamine or amino acid residues that are present in marine PL. Therefore, marine PL contain products from nonenzymatic browning and lipid oxidation reactions, namely, Strecker aldehydes, pyrroles, oxypolymers, and other impurities that may positively or negatively affect the oxidative stability and quality of marine PL. This review was undertaken to provide the industry and academia with an overview of the current understanding of the quality changes taking place in PL during their production and their storage as well as with regards to their utilization for food fortification. PMID- 26558296 TI - Improvement of SWL Efficacy: Reduction of the Respiration-Induced Kidney Motion by Using an Abdominal Compression Plate. AB - BACKGROUND AND PURPOSE: In extracorporeal shockwave lithotripsy (SWL), respiratory-induced motion of the upper urinary tract may hamper stone targeting and disintegration. The objective of this study is to analyze the effect of abdominal compression (AC) to kidney motion and to shock wave efficacy. SUBJECTS AND METHODS: The study included 10 volunteers and 10 kidney stone patients. AC was achieved by a wedge-shaped compression plate. Patients underwent a routine ultrasound-guided SWL. For analgosedation, remifentanil (~0.1 MUg/kg/min) was administered. The respiratory-induced kidney motion, as well as with free breathing and AC, was quantitatively evaluated on basis of recorded ultrasound videos. By definition, shock wave efficacy was 100%, if the stone center was aligned with the shock wave focus. Its decrease depending on off-focus distance was obtained by model stone tests. On this basis, a mean shock wave efficacy value was attributed to the displacement function resulting from each measured kidney motion. RESULTS: In volunteers, the amplitude of the displacement function with AC (mean: 8 mm; range: 3-11 mm) was significantly lower than with free breathing (mean: 12 mm; range: 5-19 mm) (paired samples t-test, p < 0.001). Correspondingly, the mean efficacy improved to 91% (range: 78%-99%) from 79% (range: 59%-94%) (p < 0.01). In the patient cohort, the amplitudes were similar and the efficacy even higher because of the respiratory depressant effect of remifentanil. By AC, the efficacy improved to 93% (range: 85%-98%) compared with 87% (range: 77%-96%) (p < 0.01). CONCLUSIONS: AC with a compression plate is easy to perform and well tolerated by patients. It significantly reduces respiratory induced kidney motion and improves shock wave efficacy. PMID- 26558297 TI - Cosolvent Effects on Solute-Solvent Hydrogen-Bond Dynamics: Ultrafast 2D IR Investigations. AB - Cosolvents strongly influence the solute-solvent interactions of biomolecules in aqueous environments and have profound effects on the stability and activity of several proteins and enzymes. Experimental studies have previously reported on the hydrogen-bond dynamics of water molecules in the presence of a cosolvent, but understanding the effects from a solute's perspective could provide greater insight into protein stability. Because carbonyl groups are abundant in biomolecules, the current study used 2D IR spectroscopy and molecular dynamics simulations to compare the hydrogen-bond dynamics of the solute's carbonyl group in aqueous solution, with and without the presence of DMSO as a cosolvent. 2D IR spectroscopy was used to quantitatively estimate the time scales of the hydrogen bond dynamics of the carbonyl group in neat water and 1:1 DMSO/water solution. The 2D IR results show spectral signatures of a chemical exchange process: The presence of the cosolvent was found to lower the hydrogen-bond exchange rate by a factor of 5. The measured exchange rates were 7.50 * 10(11) and 1.48 * 10(11) s( 1) in neat water and 1:1 DMSO/water, respectively. Molecular dynamics simulations predict a significantly shorter carbonyl hydrogen-bond lifetime in neat water than in 1:1 DMSO/water and provide molecular insights into the exchange mechanism. The binding of the cosolvent to the solute was found to be accompanied by the release of hydrogen-bonded water molecules to the bulk. The widely different hydrogen-bond lifetimes and exchange rates with and without DMSO indicate a significant change in the ultrafast hydrogen-bond dynamics in the presence of a cosolvent, which, in turn, might play an important role in the stability and activity of biomolecules. PMID- 26558298 TI - Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy. AB - INTRODUCTION: Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms. AREAS COVERED: This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA). EXPERT OPINION: Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges. PMID- 26558299 TI - A permutation based simulated annealing algorithm to predict pseudoknotted RNA secondary structures. AB - Pseudoknots are RNA tertiary structures which perform essential biological functions. This paper discusses SARNA-Predict-pk, a RNA pseudoknotted secondary structure prediction algorithm based on Simulated Annealing (SA). The research presented here extends previous work of SARNA-Predict and further examines the effect of the new algorithm to include prediction of RNA secondary structure with pseudoknots. An evaluation of the performance of SARNA-Predict-pk in terms of prediction accuracy is made via comparison with several state-of-the-art prediction algorithms using 20 individual known structures from seven RNA classes. We measured the sensitivity and specificity of nine prediction algorithms. Three of these are dynamic programming algorithms: Pseudoknot (pknotsRE), NUPACK, and pknotsRG-mfe. One is using the statistical clustering approach: Sfold and the other five are heuristic algorithms: SARNA-Predict-pk, ILM, STAR, IPknot and HotKnots algorithms. The results presented in this paper demonstrate that SARNA-Predict-pk can out-perform other state-of-the-art algorithms in terms of prediction accuracy. This supports the use of the proposed method on pseudoknotted RNA secondary structure prediction of other known structures. PMID- 26558300 TI - A comprehensive evaluation of machine learning techniques for cancer class prediction based on microarray data. AB - Prostate cancer is among the most common cancer in males and its heterogeneity is well known. The genomic level changes can be detected in gene expression data and those changes may serve as standard model for any random cancer data for class prediction. Various techniques were implied on prostate cancer data set in order to accurately predict cancer class including machine learning techniques. Large number of attributes but few numbers of samples in microarray data leads to poor training; therefore, the most challenging part is attribute reduction or non significant gene reduction. In this work, a combination of interquartile range and t-test is used for attribute reduction. Further, a comprehensive evaluation of ten state-of-the-art machine learning techniques for their accuracy in class prediction of prostate cancer is done. Out of these techniques, Bayes Network outperformed with an accuracy of 94.11% followed by Naive Bayes with an accuracy of 91.17%. PMID- 26558301 TI - Acoustic analysis of speech under stress. AB - When a person is emotionally charged, stress could be discerned in his voice. This paper presents a simplified and a non-invasive approach to detect psycho physiological stress by monitoring the acoustic modifications during a stressful conversation. Voice database consists of audio clips from eight different popular FM broadcasts wherein the host of the show vexes the subjects who are otherwise unaware of the charade. The audio clips are obtained from real-life stressful conversations (no simulated emotions). Analysis is done using PRAAT software to evaluate mean fundamental frequency (F0) and formant frequencies (F1, F2, F3, F4) both in neutral and stressed state. Results suggest that F0 increases with stress; however, formant frequency decreases with stress. Comparison of Fourier and chirp spectra of short vowel segment shows that for relaxed speech, the two spectra are similar; however, for stressed speech, they differ in the high frequency range due to increased pitch modulation. PMID- 26558302 TI - A combination of dual-tree discrete wavelet transform and minimum redundancy maximum relevance method for diagnosis of Alzheimer's disease. AB - In this paper, we propose a three-phased method for diagnosis of Alzheimer's disease using the structural magnetic resonance imaging (MRI). In first phase, gray matter tissue probability map is obtained from every brain MRI volume. Further, five regions of interest (ROIs) are extracted as per prior knowledge. In second phase, features are extracted from each ROI using 3D dual-tree discrete wavelet transform. In third phase, relevant features are selected using minimum redundancy maximum relevance features selection technique. The decision model is built with features so obtained, using a classifier. To evaluate the effectiveness of the proposed method, experiments are performed with four well known classifiers on four data sets, built from a publicly available OASIS database. The performance is evaluated in terms of sensitivity, specificity and classification accuracy. It was observed that the proposed method outperforms existing methods in terms of all three performance measures. This is further validated with statistical tests. PMID- 26558303 TI - Bioinformatics: promises and progress. AB - Bioinformatics is a multidisciplinary science that solves and analyzes biological problems. With the quantum explosion in biomedical data, the demand of bioinformatics has increased gradually. Present paper provides an overview of various ways through which the biologists or biological researchers in the domain of neurology, structural and functional biology, evolutionary biology, clinical science, etc., use bioinformatics applications for data analysis to summarise their research. A new perspective is used to classify the knowledge available in the field thus will help general audience to understand the application of bioinformatics. PMID- 26558304 TI - Advances in targeted therapy for the treatment of patients with relapsed/refractory multiple myeloma. AB - The development of proteasome inhibitors (PIs) and immunomodulatory drugs has significantly improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM); however, not all patients benefit from treatment with these agents and some patients can become drug refractory over time. Due to the largely incurable nature of multiple myeloma, the development of newer agents is ongoing and includes new oral PIs (ixazomib), immunotherapies (e.g., CD38- or SLAMF7 targeted antibodies), and small molecules. This review provides an overview of the advances in targeted therapy for patients with RRMM, including recently approved agents, with a focus on monotherapy and combined targeted therapies. PMID- 26558305 TI - Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. AB - Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes. PMID- 26558306 TI - Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5-3 Years. AB - Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5-3 years. ID was defined as serum ferritin (SF) <12 MUg/L in the absence of infection (C-reactive protein [CRP] <5 mg/L) and IDA as hemoglobin <110 g/L combined with ID. RDW (%) and the platelet count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2-6.3) to be iron deficient, compared with anemic children with a RDW <14.3%. The platelet count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children. PMID- 26558307 TI - [A novel biomarker for diagnosis of bladder cancer]. PMID- 26558308 TI - [Biomarkers for generalized pustular psoriasis and related diseases]. PMID- 26558309 TI - [Supplemental biomarker for differentiating cardioembolic stroke from the other ischemic stroke]. PMID- 26558310 TI - [A biomarker set relation to the efficacy of allergen-specific immunotherapy]. PMID- 26558311 TI - [Early childhood stress and neuropsychiatric disease]. PMID- 26558312 TI - [Industry-government - academia cooperation center for medical innovation in Hokkaido University]. PMID- 26558313 TI - [Pharmacological and clinical profiles of a novel potassium-competitive acid blocker, vonoprazan fumarate (Takecab((r)) 10 mg and 20 mg)]. PMID- 26558314 TI - [Preclinical and clinical researches of lenvatinib mesylate (Lenvima capsule), a novel antitumor agent approved for thyroid cancer treatment]. PMID- 26558315 TI - Bioactive ent-Pimarane and ent-Abietane Diterpenoids from the Whole Plants of Chloranthus henryi. AB - Two new ent-pimarane (1 and 2), eight new ent-abietane (3-10) diterpenoids, and eight known analogues (11-18) were isolated from the whole plants of Chloranthus henryi. The absolute configuration of 1 was determined on the basis of single crystal X-ray diffraction data. Compound 8 represents a class of rare naturally occurring C-14 norabietanes, and compounds 9 and 10 feature rare 13,14-seco abietane skeletons. Compounds 5, 12, 13, and 15 inhibited the yeast-to-hyphae transition of Candida albicans with IC50 values between 97.3 and 738.7 MUM. PMID- 26558316 TI - Optimism and well-being: a prospective multi-method and multi-dimensional examination of optimism as a resilience factor following the occurrence of stressful life events. AB - Optimism has been conceptualised variously as positive expectations (PE) for the future , optimistic attributions , illusion of control , and self-enhancing biases. Relatively little research has examined these multiple dimensions of optimism in relation to psychological and physical health. The current study assessed the multi-dimensional nature of optimism within a prospective vulnerability-stress framework. Initial principal component analyses revealed the following dimensions: PEs, Inferential Style (IS), Sense of Invulnerability (SI), and Overconfidence (O). Prospective follow-up analyses demonstrated that PE was associated with fewer depressive episodes and moderated the effect of stressful life events on depressive symptoms. SI also moderated the effect of life stress on anxiety symptoms. Generally, our findings indicated that optimism is a multifaceted construct and not all forms of optimism have the same effects on well-being. Specifically, our findings indicted that PE may be the most relevant to depression, whereas SI may be the most relevant to anxiety. PMID- 26558317 TI - Bioinspired pH and magnetic responsive catechol-functionalized chitosan hydrogels with tunable elastic properties. AB - We have developed pH- and magnetic-responsive hydrogels that are stabilized by both covalent bonding and catechol/Fe(3+) ligands. The viscoelastic properties of the gels are regulated by the complexation valence and can be used to tune drug release profiles. The stable incorporation of magnetic nanoparticles further expands control over the mechanical response and drug release, in addition to providing magnetic stimuli-responsivity to the gels. PMID- 26558319 TI - Diastereoselective Synthesis of alpha-Quaternary Aziridine-2-carboxylates via Aza Corey-Chaykovsky Aziridination of N-tert-Butanesulfinyl Ketimino Esters. AB - A general, scalable, and highly diastereoselective aziridination of N-tert butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant alpha-quaternary amino esters and derivatives starting from readily available precursors. PMID- 26558320 TI - Hypoallergenic molecules for subcutaneous immunotherapy. AB - Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field. PMID- 26558318 TI - The multiple faces of RAGE--opportunities for therapeutic intervention in aging and chronic disease. AB - INTRODUCTION: This review focuses on the multi-ligand receptor of the immunoglobulin superfamily--receptor for advanced glycation endproducts (RAGE). The accumulation of the multiple ligands of RAGE in cellular stress milieux links RAGE to the pathobiology of chronic disease and natural aging. AREAS COVERED: In this review, we present a discussion on the ligands of RAGE and the implications of these ligand families in disease. We review the recent literature on the role of ligand-RAGE interaction in the consequences of natural aging; the macro- and microvascular complications of diabetes; obesity and insulin resistance; autoimmune disorders and chronic inflammation; and tumors and Alzheimer's disease. We discuss the mechanisms of RAGE signaling through its intracellular binding effector molecule--the formin DIAPH1. Physicochemical evidence of how the RAGE cytoplasmic domain binds to the FH1 (formin homology 1) domain of DIAPH1, and the consequences thereof, are also reviewed. EXPERT OPINION: We discuss the modalities of RAGE antagonism currently in preclinical and clinical studies. Finally, we present the rationale behind potentially targeting the RAGE cytoplasmic domain-DIAPH1 interaction as a logical strategy for therapeutic intervention in the pathological settings of chronic diseases and aging wherein RAGE ligands accumulate and signal. PMID- 26558321 TI - Disease Recurrence and Second Tumors in Long-term Survivors of Lung Cancer. AB - INTRODUCTION AND OBJECTIVES: As cancer survival improves, the appearance of multiple tumors in a single patient is becoming more common. The aim of this study was to analyze long-term evolution, focusing particularly on disease recurrence and second primary tumors, in patients with lung cancer (LC) and >= 3 years overall survival. MATERIAL AND METHODS: Retrospective study of 1,769 patients with LC. A total of 218 (136 treated with surgery and 82 with other treatments), followed up for between 5 and 23 years were enrolled. LC progress and intercurrent diseases were recorded. RESULTS: A total of 65 patients presented tumor relapse, of which 60.9% occurred in the first 3 years; 26 patients developed secondary primary tumors (84.6% after 5 years) and 24 developed 2 or more second extrapulmonary tumors (66.6% after 5 years), most of which were smoking-related. The incidence of second primaries was greater than the expected incidence of cancer in the general population matched for age and sex. CONCLUSION: The multiple carcinogenic effect of smoking persists and manifests in various organs, more than 5 years after the diagnosis of LC, even in patients with long survival. After 5 years, a second tumor is more likely than a relapse of the primary disease, and the lung is the most common site of development of a second tumor. PMID- 26558322 TI - Study of contact characteristics between a respirator and a headform. AB - This article presents a computational study on contact characteristics of contact pressure and resultant deformation between an N95 filtering facepiece respirator and a newly developed digital headform. The geometry of the headform model is obtained based on computed tomography scanning of a volunteer. The segmentation and reconstruction of the headform model is performed by Mimics v16.0 (Materialise, Leuven, Belgium), which is a medical image processing software. The respirator model is obtained by scanning the surface of a 3M 8210 N95 respirator using a 3D digitizer and then the model is transformed by Geomagic Studio v12.0 (3D system, Rock Hill, SC), a reverse engineering software. The headform model contains a soft tissue layer, a skull layer, and a separate nose. The respirator model contains two layers (an inner face sealing layer and an outer layer) and a nose clip. Both the headform and respirator are modeled as solid elements and are deformable. The commercial software, LS-DYNA (LSTC, Livermore, CA), is used to simulate the contact between the respirator and headform. Contact pressures and resultant deformation of the headform are investigated. Effects of respirator stiffness on contact characteristics are also studied. A Matlab (MathWorks, Natick, MA) program is developed to calculate local gaps between the headform and respirator in the stable wearing state. PMID- 26558324 TI - Protein electron transfer: is biology (thermo)dynamic? AB - Simple physical mechanisms are behind the flow of energy in all forms of life. Energy comes to living systems through electrons occupying high-energy states, either from food (respiratory chains) or from light (photosynthesis). This energy is transformed into the cross-membrane proton-motive force that eventually drives all biochemistry of the cell. Life's ability to transfer electrons over large distances with nearly zero loss of free energy is puzzling and has not been accomplished in synthetic systems. The focus of this review is on how this energetic efficiency is realized. General physical mechanisms and interactions that allow proteins to fold into compact water-soluble structures are also responsible for a rugged landscape of energy states and a broad distribution of relaxation times. Specific to a protein as a fluctuating thermal bath is the protein-water interface, which is heterogeneous both dynamically and structurally. The spectrum of interfacial fluctuations is a consequence of protein's elastic flexibility combined with a high density of surface charges polarizing water dipoles into surface nanodomains. Electrostatics is critical to the protein function and the relevant questions are: (i) What is the spectrum of interfacial electrostatic fluctuations? (ii) Does the interfacial biological water produce electrostatic signatures specific to proteins? (iii) How is protein mediated chemistry affected by electrostatics? These questions connect the fluctuation spectrum to the dynamical control of chemical reactivity, i.e. the dependence of the activation free energy of the reaction on the dynamics of the bath. Ergodicity is often broken in protein-driven reactions and thermodynamic free energies become irrelevant. Continuous ergodicity breaking in a dense spectrum of relaxation times requires using dynamically restricted ensembles to calculate statistical averages. When applied to the calculation of the rates, this formalism leads to the nonergodic activated kinetics, which extends the transition-state theory to dynamically dispersive media. Releasing the grip of thermodynamics in kinetic calculations through nonergodicity provides the mechanism for an efficient optimization between reaction rates and the spectrum of relaxation times of the protein-water thermal bath. Bath dynamics, it appears, play as important role as the free energy in optimizing biology's performance. PMID- 26558323 TI - DIRECT-ID: An automated method to identify and quantify conformational variations -application to beta2 -adrenergic GPCR. AB - The conformational dynamics of a macromolecule can be modulated by a number of factors, including changes in environment, ligand binding, and interactions with other macromolecules, among others. We present a method that quantifies the differences in macromolecular conformational dynamics and automatically extracts the structural features responsible for these changes. Given a set of molecular dynamics (MD) simulations of a macromolecule, the norms of the differences in covariance matrices are calculated for each pair of trajectories. A matrix of these norms thus quantifies the differences in conformational dynamics across the set of simulations. For each pair of trajectories, covariance difference matrices are parsed to extract structural elements that undergo changes in conformational properties. As a demonstration of its applicability to biomacromolecular systems, the method, referred to as DIRECT-ID, was used to identify relevant ligand modulated structural variations in the beta2 -adrenergic (beta2 AR) G-protein coupled receptor. Micro-second MD simulations of the beta2 AR in an explicit lipid bilayer were run in the apo state and complexed with the ligands: BI-167107 (agonist), epinephrine (agonist), salbutamol (long-acting partial agonist), or carazolol (inverse agonist). Each ligand modulated the conformational dynamics of beta2 AR differently and DIRECT-ID analysis of the inverse-agonist vs. agonist modulated beta2 AR identified residues known through previous studies to selectively propagate deactivation/activation information, along with some previously unidentified ligand-specific microswitches across the GPCR. This study demonstrates the utility of DIRECT-ID to rapidly extract functionally relevant conformational dynamics information from extended MD simulations of large and complex macromolecular systems. PMID- 26558325 TI - Nanostructured gold microelectrodes for SERS and EIS measurements by incorporating ZnO nanorod growth with electroplating. AB - In this paper, a fine gold nanostructure synthesized on selective planar microelectrodes in micro-chip is realized by using an advanced hybrid fabrication approach incorporating growth of nanorods (NRs) with gold electroplating. By this developed nanostructure, integration of in-situ surface-enhanced Raman spectroscopy (SERS) detection with electrochemical impedance spectroscopy (EIS) measurement for label-free, nondestructive, real-time and rapid monitoring on a single cell has been achieved. Moreover, parameters of Au nanostructures such as size of nanoholes/nanogaps can be controllably adjusted in the fabrication. We have demonstrated a SERS enhancement factor of up to ~2.24 * 10(6) and double layer impedance decrease ratio of 90% ~ 95% at low frequency range below 200 kHz by using nanostructured microelectrodes. SERS detection and in-situ EIS measurement of a trapped single cell by using planar microelectrodes are realized to demonstrate the compatibility, multi-functions, high-sensitivity and simplicity of the micro-chip system. This dual function platform integrating SERS and EIS is of great significance in biological, biochemical and biomedical applications. PMID- 26558326 TI - [Not Available]. PMID- 26558327 TI - The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system. AB - The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses. PMID- 26558328 TI - Disease-free survival after salvage therapy for recurrent oropharyngeal squamous cell carcinoma. AB - BACKGROUND: Factors associated with disease-free survival (DFS) after salvage therapy for recurrent oropharyngeal squamous cell carcinoma (SCC) in the context of human papillomavirus (HPV) are poorly understood. METHODS: A retrospective cohort analysis was conducted of patients with recurrent oropharyngeal SCC with known HPV tumor status who received salvage therapy. RESULTS: Eighty-six patients were eligible for analysis. Sixty-four patients (74%) were HPV-positive. In multivariable analysis, HPV-positive tumor status (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.13-0.71; p = .007), clinical response to any salvage therapy (HR = 0.29; 95% CI = 0.11-0.77; p = .01), and surgical salvage (HR = 0.38; 95% CI = 0.16-0.88; p = .02) were associated with improved overall survival (OS). Positive surgical margin was associated with worse DFS after salvage (HR = 8.43; 95% CI = 1.99-35.70; p = .004). CONCLUSION: For recurrent oropharyngeal SCC, HPV-positive tumor status, surgical salvage, and clinical response to salvage therapy are independently associated with improved OS, but not DFS after salvage. Surgical margin is the only independent predictor of DFS. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1501-E1509, 2016. PMID- 26558329 TI - Nitroglycerin for management of retained placenta. AB - BACKGROUND: Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. OBJECTIVES: To evaluate the benefits and harms of NTG as a tocolytic, either alone or in addition to uterotonics, in the management of retained placenta. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2015), reference lists of retrieved studies and contacted experts in the field. SELECTION CRITERIA: Any adequately randomised controlled trial (RCT) comparing the use of NTG, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included three randomised controlled trials (RCTs) with 175 women. The three published RCTs compared NTG alone versus placebo. The detachment status of retained placenta was unknown in all three RCTs. Collectively, among the three included trials, two were judged to be at low risk of bias and the third trial was judged to be at high risk of bias for two domains: incomplete outcome data and selective reporting. The three trials reported seven out of 23 of the review's pre-specified outcomes.The primary outcome "manual removal of the placenta" was reported in all three studies. No differences were seen between NTG and placebo for manual removal of the placenta (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 to 1.46; women = 175; I2 = 81%). A random-effects model was used because of evidence of substantial heterogeneity in the analysis. There were also no differences between groups for risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62 to 1.39; women = 150; studies = two; I2 = 0%). Blood transfusion was only reported in one study (40 women) and again there was no difference between groups (RR 1.00, 95% CI 0.07 to 14.90; women = 40; I2 = 0%). Mean blood loss (mL) was reported in the three studies and no differences were observed (mean difference (MD) -115.31, 95% CI -306.25 to 75.63; women = 169; I2 = 83%). Nitroglycerin administration was not associated with an increase in headaches (RR 1.09, 95% CI 0.80 to 1.47; women = 174; studies = three; I2 = 0%). However, nitroglycerin administration was associated with a significant, though mild, decrease in systolic and diastolic blood pressure and a significant increase in pulse rate (MD -3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per minute) respectively (reported by only one study including 24 participants). Maternal mortality and addition of therapeutic uterotonics were not reported in any study. AUTHORS' CONCLUSIONS: In cases of retained placenta, currently available data showed that the use of NTG alone did not reduce the need for manual removal of placenta. This intervention did not increase the incidence of severe postpartum haemorrhage nor the need for blood transfusion. Haemodynamically, NTG had a significant though mild effect on both pulse rate and blood pressure. PMID- 26558330 TI - Genital Trichomonas vaginalis is rare among female attendees at a Sydney metropolitan sexual health clinic. PMID- 26558331 TI - Cardiovascular risk in pulmonary alveolar proteinosis. AB - We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies. PMID- 26558332 TI - Inflammation in tissue engineering: The Janus between engraftment and rejection. AB - Tissue engineering (TE) for tissue and organ regeneration or replacement is generally performed with scaffold implants, which provide structural and molecular support to in vitro seeded or in vivo recruited cells. TE implants elicit the host immune response, often resulting in engraftment impediment or rejection. Besides this negative effect, however, the immune system components also yield a positive influence on stem cell recruitment and differentiation, allowing tissue regeneration and healing. Thus, a balanced cooperation between proinflammatory and proresolution players of the immune response is an essential element of implant success. In this context, macrophage plasticity plays a fundamental role. Therefore modulating the immune response, instead of immune suppressing the host, might be the best way to successfully implant TE tissues or organs. In particular, it is becoming evident that the scaffold, immune, and stem cells are linked by a three-way interaction, and many efforts are being made for scaffold-appropriate design and functionalization in order to drive the inflammation process toward regeneration, vascularization, and implant success. This review discusses current and potential strategies for inflammation modulation to aid engraftment and regeneration, supporting the concept that quality, and not quantity, of inflammation might influence implant success. PMID- 26558333 TI - [The coordination betwen health and social services in the care of people with severe mental disorders]. AB - Coordination between health and social services is a key point in caring for an increasing number of people affected by different types of health problems. The change in demographic and epidemiological patterns in our societies evidences the need of this coordination, usually not covered by our care systems. A sector in which the coordination is particularly important is the care of people with disabilities related to the suffering from severe mental disorders. This is a field that has been too long on the sidelines of the general health and social care systems as a result of the social stigma and traditional psychiatric institutions, setting in motion a vicious circle that must be broken in order to identify and to respond to the needs of such persons. In fact, the processes of change towards community care, with targets for recovery and not mere palliative or marginalizing care, necessarily incorporate this coordination as a cornerstone strategy for social inclusion and citizenship. Although there are still significant gaps in this regard, especially in Spain. However, there are experiences of change, such as that of Andalusia, which set the tone for the development of a strategy for integrated care, whose foundations and main elements we try to summarize in the present article. PMID- 26558334 TI - [Predictors of cognitive impairment in population over 64 years institutionalized and non-institutionalized]. AB - AIM: Describe the factors which can be associated with cognitive impairment in institutionalized and non-institutionalized elderly. METHOD: Cross-sectional study of 200 people aged over 64 in Huelva (Spain) in 2014. Of these, 100 people were institutionalized in a residential facility and 100 were not. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE-35), basic activities of daily living by Barthel index, general health through the Goldberg GHQ-28 and social, clinical and behavioural variables were contemplated in the study. The association of cognitive impairment with all the variables was analysed using Chi-square test. Finally, a multivariate analysis was performed using logistic regression to identify possible joint influence of variables to study on the cognitive impairment. RESULTS: The prevalence of cognitive impairment in those institutionalized was 47%, higher than that of non institutionalized group which was only 8% (p<.001). The dependence for basic activities for daily living and learning activities were the only variables in both groups which were associated with the cognitive impairment. Institutionalization (OR=5.368), age (OR=1.066) and dependence for basic activities (OR=5.036) were negatively associated with CI, while learning activities (OR=.227) were associated in a positive way. CONCLUSIONS: Conducting learning activities and the promotion of personal autonomy can delay cognitive impairment in older people. It is important to include cognitive stimulation programs aimed at the old population, especially in residential institutions. PMID- 26558335 TI - In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency. AB - INTRODUCTION: Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis. AIM: To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL(-1) ). METHODS: Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3). RESULTS: Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven((r)) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg( 1) ): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven((r)) exceeded the reference range. At lower dose (5 U kg(-1) ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven((r)) normalized the ETP but exceeded the reference range with other parameters. CONCLUSION: Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement. PMID- 26558336 TI - In Situ Analysis of Small Populations of Adherent Mammalian Cells Using Laser Ablation Electrospray Ionization Mass Spectrometry in Transmission Geometry. AB - Most cultured cells used for biomedical research are cultured adherently, and the requisite detachment prior to biochemical analysis might induce chemical changes. This is especially crucial if accurate metabolic measurements are desired, given the rapid turnover of metabolites in living organisms. There are only a few methods available for the nontargeted in situ analysis of small adherent cell populations. Here we show that laser ablation electrospray ionization (LAESI) mass spectrometry (MS) can be used to analyze adherent cells directly, while still attached to the culture surface. To reduce the size of the analyzed cell population, the spot size constraints of conventional focusing in reflection geometry (rg) LAESI had to be eliminated. By introducing transmission geometry (tg) LAESI and incorporating an objective with a high numerical aperture, spot sizes of 10-20 MUm were readily achieved. As few as five adherent cells could be specifically selected for analysis in their culturing environment. The importance of in situ analysis was highlighted by comparing the metabolite composition of adherent versus suspended cells. For example, we observed that cells analyzed adherently yielded higher values for the adenylate energy charge (0.90 +/- 0.09 for adherent cells vs 0.09 +/- 0.03 for suspended cells). Additionally, due to the smaller focal spot size, tg-LAESI enabled the analysis of ~20 times smaller cell populations compared to rg-LAESI. PMID- 26558337 TI - Enhanced Photoelectrochemical Oxygen Evolution Reaction Ability of Iron-Derived Hematite Photoanode with Titanium Modification. AB - A facile fabrication route towards a titanium-modified hematite photoanode has been developed, and the photoelectrochemical properties of this anode have been evaluated. Compared to pristine hematite, the activity of the modified photoanode in this work delivered almost twofold higher photocurrent under Air Mass 1.5G illumination. Further research revealed that the enhanced performance of the hematite photoanode with a titanium-modified surface resulted from the dominant impact of heterojunction formation and suppressed surface recombination, supplemented by a slightly improved light-harnessing ability. PMID- 26558339 TI - What is the most possible cause of the side branch occlusion after bioabsorbable everolimus-eluting stent implantation?: Thickness of the scaffolds or large plaque burden? PMID- 26558340 TI - Prevention of preterm birth with vaginal progesterone or 17-alpha hydroxyprogesterone caproate: a critical examination of efficacy and safety. AB - Progestogens are the first drugs to demonstrate reproducibly a reduction in the rate of early preterm birth. The efficacy and safety of progestogens are related to individual pharmacologic properties of each drug within this class of medication and characteristics of the population that is treated. The synthetic 17-hydroxyprogesterone caproate and natural progesterone have been studied with the use of a prophylactic strategy in women with a history of preterm birth and in women with a multiple gestation. Evidence from a single large comparative efficacy trial suggests that vaginal natural progesterone is superior to 17 hydroxyprogesterone caproate as a prophylactic treatment in women with a history of mid-trimester preterm birth. Progestogen therapy is indicated for women with this highest risk profile based on evidence from 2 trials. A therapeutic approach based on the identification of a sonographic short cervix has been studied in several phase III trials. Independent phase III trials and an individual patient metaanalysis suggest that vaginal progesterone is efficacious and safe in women with a singleton and a short cervix. Two trials that tested 17 hydroxyprogesterone caproate in women with a short cervix showed no benefit. No consistent benefit for the prophylactic or therapeutic use of progestogens has been demonstrated in larger trials of women whose pregnancies were complicated by a multiple gestation (twins or triplets), preterm labor, or preterm rupture of membranes. Unfortunately, several large randomized trials in multiple gestations have identified harm related to 17-hydroxyprogesterone caproate exposure, and the synthetic drug is contraindicated in this population. The current body of evidence is evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines to derive the strength of recommendation in each of these populations. A large confirmatory trial that is testing 17 hydroxyprogesterone caproate exposure in women with a singleton pregnancy and a history of preterm birth is near completion. Additional study of the efficacy and safety of progestogens is suggested in well-selected populations based on the presence of biomarkers. PMID- 26558341 TI - Rapid whole genome sequencing of Miyazaki-Bali/2007 Pteropine orthoreovirus by modified rolling circular amplification with adaptor ligation - next generation sequencing. AB - The emergence of orthoreoviruses as the causative agent of human respiratory illness over the past few years has led to a demand to determine their viral genome sequences. The whole genome sequencing of such RNA viruses using traditional methods, such as Sanger dideoxy sequencing following rapid amplification of cDNA ends presents a laborious challenge due to the numerous preparatory steps required before sequencing can commence. We developed a practical, time-efficient novel combination method capable of reducing the total time required from months to less than a week in the determination of whole genome sequence of Pteropine orthoreoviruses (PRV); through a combination of viral RNA purification and enrichment, adaptor ligation, reverse transcription, cDNA circularization and amplification, and next generation sequencing. We propose to call the method "modified rolling circular amplification with adaptor ligation - next generation sequencing (mRCA-NGS)". Here, we describe the technological focus and advantage of mRCA-NGS and its expansive application, exemplified through the phylogenetic understanding of the Miyazaki-Bali/2007 PRV. PMID- 26558342 TI - Arterial Injury as a Result of Mowing Clover. PMID- 26558343 TI - Endovascular Treatment of Double Hepatic Arterial Aneurysm. PMID- 26558344 TI - System for measuring oxygen consumption rates of mammalian cells in static culture under hypoxic conditions. AB - Estimating the oxygen consumption rates (OCRs) of mammalian cells in hypoxic environments is essential for designing and developing a three-dimensional (3-D) cell culture system. However, OCR measurements under hypoxic conditions are infrequently reported in the literature. Here, we developed a system for measuring OCRs at low oxygen levels. The system injects nitrogen gas into the environment and measures the oxygen concentration by an optical oxygen microsensor that consumes no oxygen. The developed system was applied to HepG2 cells in static culture. Specifically, we measured the spatial profiles of the local dissolved oxygen concentration in the medium, then estimated the OCRs of the cells. The OCRs, and also the pericellular oxygen concentrations, decreased nonlinearly as the oxygen partial pressure in the environment decreased from 19% to 1%. The OCRs also depended on the culture period and the matrix used for coating the dish surface. Using this system, we can precisely estimate the OCRs of various cell types under environments that mimic 3-D culture conditions, contributing crucial data for an efficient 3-D culture system design. PMID- 26558345 TI - Statistical approaches to account for false-positive errors in environmental DNA samples. AB - Environmental DNA (eDNA) sampling is prone to both false-positive and false negative errors. We review statistical methods to account for such errors in the analysis of eDNA data and use simulations to compare the performance of different modelling approaches. Our simulations illustrate that even low false-positive rates can produce biased estimates of occupancy and detectability. We further show that removing or classifying single PCR detections in an ad hoc manner under the suspicion that such records represent false positives, as sometimes advocated in the eDNA literature, also results in biased estimation of occupancy, detectability and false-positive rates. We advocate alternative approaches to account for false-positive errors that rely on prior information, or the collection of ancillary detection data at a subset of sites using a sampling method that is not prone to false-positive errors. We illustrate the advantages of these approaches over ad hoc classifications of detections and provide practical advice and code for fitting these models in maximum likelihood and Bayesian frameworks. Given the severe bias induced by false-negative and false positive errors, the methods presented here should be more routinely adopted in eDNA studies. PMID- 26558346 TI - Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases. AB - Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches. PMID- 26558347 TI - Effect of health education on trainee teachers' knowledge, attitudes, and first aid management of epilepsy: An interventional study. AB - PURPOSE: High rates of poor knowledge of, and negative attitudes towards people with epilepsy (PWE) are generally found among school teachers. Their first aid epilepsy management skills are poor. It remains unknown if this is different among trainee teachers and whether educational intervention might reduce these rates. We examined the effect of health education on the knowledge, attitudes, and first aid management of epilepsy on trainee teachers in Nigeria. METHODS: Baseline data and socio-demographic determinants were collected from 226 randomly selected trainee teachers, at the Federal College of Education, Lagos, Nigeria, with self-administered questionnaires. They received a health intervention comprising an hour and half epilepsy lecture followed by a discussion. Baseline knowledge of, and attitudes towards PWE and their first aid epilepsy management skills were compared to post-interventional follow-up data collected twelve weeks later with similar questionnaires. RESULTS: At baseline the majority (61.9%) and largest proportion (44.2%) of respondents had negative attitudes and poor knowledge of epilepsy, respectively. The knowledge of, and attitudes towards epilepsy, and the first aid management skill increased in most respondents, post intervention. The proportion of respondents with poor knowledge and negative attitudes dropped by 15.5% (p<0.0001) and 16.4% (p<0.0001) respectively. Correct knowledge concomitantly increased by 29.6% (p<0.0001) and good first aid management skills increased by 25.0% (p<0.0001) from baseline. CONCLUSION: Epilepsy health education could increase trainee teachers' knowledge of, and attitudes towards epilepsy and facilitate correct first aid management. This emphasizes the potential benefit of incorporating an epilepsy tailored intervention programme into teachers' training curricula. PMID- 26558349 TI - Pilot study to evaluate a novel three-dimensional wound measurement device. AB - As the burden of diabetes continues to grow and treatment standards require careful tracking of wound progress, clinicians increasingly need to rely on technological improvements in wound measurement technologies to track the progress of their treatments. This study aims to determine the accuracy of a new three-dimensional wound measurement (3DWM) device against laser-assisted wound measurement (LAWM) devices and traditional methods of wound measurement. Using several wound models, we demonstrate that the 3DWM device measures wound area, depth and volume similarly to the other methods tested. This is especially apparent when changes in wound measurements were compared between the two devices. Differences between the two technologies were apparent when analysing wound measurement time and measurement repeatability. There was a significantly lower incidence of error in measurements between the 3DWM device and the LAWM device. Finally, the measurement time was significantly faster with the 3DWM device compared to the LAWM device. Together, these data demonstrate that the 3DWM device provides an accurate and reproducible method for measuring changes in wound healing similar to other available technologies. Further, the use of the 3DWM device provides a faster and more consistent measurement, which is critical for clinical application and use. PMID- 26558350 TI - Integration of coal gasification and waste heat recovery from high temperature steel slags: an emerging strategy to emission reduction. AB - With the continuous urbanization and industrialization in the world, energy saving and greenhouse gas (GHG) emission reduction have been serious issues to be addressed, for which heat recovery from traditional energy-intensive industries makes up a significant strategy. Here we report a novel approach to extract the waste heat and iron from high temperature steel slags (1450-1650 (o)C) produced in the steel industry, i.e., integration of coal gasification and steel slag treatment. Both the thermodynamics and kinetics of the pertinent reactions were identified. It was clarified that the kinetic mechanism for gasification varied from A2 model to A4 model (Avrami-Erofeev) in the presence of slags. Most importantly, the steel slags acted not only as good heat carriers but also as effective catalysts where the apparent activation energy for char gasification got remarkably reduced from 95.7 kJ/mol to 12.1 kJ/mol (A2 model). Furthermore, the FeO in the slags was found to be oxidized into Fe3O4, with an extra energy release, which offered a potential for magnetic separation. Moreover, based on the present research results, an emerging concept, composed of multiple industrial sectors, was proposed, which could serve as an important route to deal with the severe environmental problems in modern society. PMID- 26558348 TI - Alcohol-induced alterations in dopamine modulation of prefrontal activity. AB - Long-term alcohol use leads to persistent cognitive deficits that may be associated with maladaptive changes in the neurocircuitry that mediates executive functions. Impairments caused by these changes can persist well into abstinence and have a negative impact on quality of life and job performance, and can increase the probability of relapse. Many of the changes that affect cognitive function appear to involve dysregulation of the mesocortical dopamine system. This includes changes in dopamine release and alterations in dopamine receptor expression and function in the medial prefrontal cortex (PFC). This review summarizes the cellular effects of acute and chronic ethanol exposure on dopamine release and dopamine receptor function in the PFC with the goal of providing greater understanding of the effects of alcohol-use disorders on the dopamine system and how this relates to deficits in the executive function of the PFC. PMID- 26558351 TI - Incidence of Suicide Among Persons Who Had a Parent Who Died During Their Childhood: A Population-Based Cohort Study. AB - IMPORTANCE: Parental death from suicide is associated with increased risk of suicide in the bereaved child, but little is known about the long-term risks of suicide after parental death from other causes. A better understanding of this association may improve suicide prevention efforts. OBJECTIVE: To examine the long-term risks of suicide after parental death and how the risk trajectories differed by cause of parental death while accounting for major potential confounding variables. DESIGN, SETTING, AND PARTICIPANTS: A population-based matched cohort study was performed using information from nationwide registers (data from 1968 to 2008) in 3 Scandinavian countries (for a total of 7,302,033 persons). We identified 189,094 children (2.6%) who had a parent who died before the child reached 18 years of age (ie, the bereaved cohort). Each bereaved child was matched by sex and age to 10 children who did not have a parent who died before they reached 18 years of age (for a total of 1,890,940 children) (ie, the reference cohort). Both cohorts were followed for up to 40 years. Poisson regression was used to calculate the incidence rate ratio (IRR), while accounting for age at parental death, sex, time since bereavement, maternal/paternal death, birth order, family history of psychiatric illness, and socioeconomic status. Data analyses were finalized June 24, 2015. EXPOSURE: The main exposure was death of a parent within the first 18 years of life. MAIN OUTCOMES AND MEASURES: Incidence of suicide among persons who had a parent who died during their childhood. RESULTS: During follow-up, 265 bereaved persons (0.14%) and 1342 nonbereaved persons (0.07%) died of suicide (IRR = 2.02 [95% CI, 1.75-2.34]); IRR = 3.44 (95% CI, 2.61-4.52) for children who had a parent who died of suicide, and IRR = 1.76 (95% CI, 1.49-2.09) for children who had a parent who died of other causes. The IRR tended to be higher for children who had a parent who died before they reached 6 years of age, and the IRR remained high for at least 25 years. During 25 years of follow-up, the absolute risk of suicide was 4 in 1000 persons for boys who experienced parental death and 2 in 1000 persons for girls who experienced parental death. CONCLUSIONS AND RELEVANCE: Parental death in childhood is, irrespective of cause, associated with an increased long-term risk of suicide. The consequences of parental death in childhood are far-reaching, and suicide risk trajectories may be influenced by early-life conditions. Future public health efforts should consider helping highly distressed children to cope with bereavement. PMID- 26558352 TI - LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations. AB - INTRODUCTION: Chronic lymphocytic leukemia is a heterogeneous yet incurable disease. Whole-genome and whole-exome sequencing studies have revealed recurrently occurring somatic mutations in some genes. Several other prognostic markers have previously been tested for their prognostic value in CLL. LPL is among these markers. AIM: To evaluate LPL gene expression together with the well established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. METHODS: On 149 patients, LPL gene expression was analyzed by real-time RT-PCR. Exon 34 of NOTCH1 was PCR-amplified and directly sequenced. RESULTS: LPL gene expression could be measured as a categorical variable (LPL+/LPL-) and was associated with time to treatment (P < 0.001) and overall survival (P = 0.007). In patients otherwise classified as having a good prognosis according to established and new prognostic markers, 3 of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (P = 0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (P = 0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. CONCLUSIONS: NOTCH1 mutations are tightly associated with LPL gene expression. LPL expression is independently associated with poor outcome in CLL and can be measured as a categorical variable. PMID- 26558353 TI - Body weight gain during adulthood and uterine myomas: Pro-Saude Study. AB - This study intended to investigate whether body weight gain during adulthood is associated with uterine myomas. 1,560 subjects were evaluated in a Pro-Saude Study. Weight gain was evaluated in a continuous fashion and also in quintiles. Odds ratios and 95% confidence intervals were estimated through logistic regression models that were adjusted for education levels, color/race, body mass indices at age 20, age of menarche, parity, use of oral contraceptive methods, smoking, health insurance, and the Papanicolaou tests. No relevant differences were observed regarding the presence of uterine myomas among weight gain quintiles in that studied population. PMID- 26558354 TI - Evaluating genomic divergence and parallelism in replicate ecomorphs from young and old cichlid adaptive radiations. AB - Comparative genomic studies of closely related species typically focus on single species pairs at one given stage of divergence. That makes it difficult to infer the continuum of evolutionary process during speciation and beyond. Here, we use whole-genome resequencing to examine genomic patterns of divergence in three sympatric cichlid species pairs with very similar functional and ecological differentiation, but different ages. We find a strong signature of increasing genomic divergence with time in both the mitochondrial genome and the nuclear genome. In contrast to many other systems, we find that in these cichlids, regions of elevated relative differentiation also exhibit increased absolute differentiation. We detect a signature of convergent evolution in a comparison of outlier regions across all three species pair comparisons, but the extent of it is modest, and regions that are strongly divergent in any one pair tend to be only slightly elevated in the other pairs, consistent with a repeatable but polygenic basis of traits that characterize the ecomorphs. Our results suggest that strong functional phenotypic differentiation, as seen in all three species pairs, is generally associated with a clear signature of genomic divergence, even in the youngest species pair. PMID- 26558356 TI - Patient-controlled Analgesia With Propacetamol-Fentanyl Mixture for Prevention of Postoperative Nausea and Vomiting in High-risk Patients Undergoing Spine Surgery: A Randomized Controlled Trial. AB - BACKGROUND: This randomized trial evaluated the effect of intravenous patient controlled analgesia (IV-PCA) based on fentanyl mixed with either propacetamol or an equivalent volume of normal saline on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing spinal surgery. MATERIALS AND METHODS: One hundred eight nonsmoking female patients were randomly and evenly allocated to receive IV-PCA with either propacetamol (4 g) or normal saline mixed to fentanyl (20 MUg/kg). Primary study outcome was PONV incidence at 24 hours postsurgery. Secondary outcomes were nausea severity, pain intensity (100-mm visual analog scale), use of rescue antiemetics and analgesics, patient satisfaction, and adverse events at 6, 12, and 24 hours postsurgery. RESULTS: Postsurgery, the propacetamol versus normal saline group had lower PONV incidence at 24 hours (41% vs. 66%, P=0.011); pain intensity at rest and rescue analgesic requirements at 6 to 12 hours (30+/-15 vs. 41+/-19, P=0.008; and 25% vs. 49%, P=0.036, respectively) and at 12 to 24 hours (25+/-15 vs. 35+/-17, P=0.008; and 19% vs. 42%, P=0.044, respectively); and higher patient satisfaction score (6.4+/ 1.4 vs. 5.7+/-1.8, P=0.028). CONCLUSIONS: In patients undergoing spinal surgery and at risk of developing PONV, continuous IV-PCA based on propacetamol mixed to fentanyl, relative to fentanyl alone, effectively reduced the incidence of PONV, pain intensity at rest, and additional use of rescue analgesics with higher patient satisfaction. PMID- 26558357 TI - Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation. AB - The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation. PMID- 26558358 TI - Advance care planning for nursing home residents with dementia: policy vs. practice. AB - AIMS: The aims of this study were: to evaluate the advance care planning policy for people with dementia in nursing homes; to gain insight in the involvement of residents with dementia and their families in advance care planning, and in the relationship between the policy and the actual practice of advance care planning. BACKGROUND: Through advance care planning, nursing home residents with dementia are involved in care decisions, anticipating their reduced decision-making capacity. However, advance care planning is rarely realized for this group. Prevalence and outcomes have been researched, but hardly any research has focused on the involvement of residents/families in advance care planning. DESIGN: Observational cross-sectional study in 20 nursing homes. METHODS: The ACP audit assessed the views of the nursing homes' staff on the advance care planning policy. In addition, individual conversations were analysed with 'ACP criteria' (realization of advance care planning) and the 'OPTION' instrument (involvement of residents/families). DATA COLLECTION: June 2013-September 2013. RESULTS: Nursing homes generally met three quarters of the pre-defined criteria for advance care planning policy. In almost half of the conversations, advance care planning was explained and discussed substantively. Generally, healthcare professionals only managed to involve residents/families on a baseline skill level. There were no statistically significant correlations between policy and practice. CONCLUSION: The evaluations of the policy were promising, but the actual practice needs improvement. Future assessment of both policy and practice is recommended. Further research should focus on communication interventions for implementing advance care planning in the daily practice. PMID- 26558359 TI - A novel genetic- and cell-based tool for assessing the efficacy and toxicity of anticancer drugs in vitro. AB - AIMS: To develop an in vitro tool for assessing the efficacy and toxicity of anticancer drugs using mixed culture containing both tumor and non-tumor cells. Such in vitro tool should have high application potential in drug-screening and personalized cancer care. METHODS: Fibroblasts were spiked as non-tumor cells into tumor cells of an established line. The mixed culture was treated with a test drug at various concentrations. After the treatment, DNA was prepared directly from the survived adhesive cells in the wells of the 96-well plates using a simple and inexpensive method, and subjected to digital PCR for measuring relative copy numbers of a target gene NF1 to that of a reference gene RPP30. The NF1 gene is known to be heterozygously deleted in these tumor cells while the RPP30 gene has two copies in both tumor and non-tumor cells. Using the NF1/ RPP30 ratios resulting from the dual digital PCR assay, the proportions of tumor cells were calculated for each drug concentration. RESULTS: Digital PCR confirmed that the tumor cells have only one copy of the NF1 gene while the non-tumor fibroblasts have two copies. By contrast, both types of cells have two copies of the reference gene RPP30. Using the ratio of the two genes, we successfully calculated the proportion of tumor cells which decreased as the dose of the test drug increased up to a certain concentration, indicating that the drug is more effective for the tumor cells than for the non-tumor cells in this dose-range. At the highest dose, we observed a slight increase in the proportion of tumor cells, likely reflecting the toxic effect of the drug on both tumor and non-tumor cells. CONCLUSION: This pilot study demonstrated the feasibility of a genetic- and cell based tool for testing efficacy and toxicity of anticancer drugs in vitro. The promising results suggest that additional efforts are merited, for further development since such a tool will likely have high application potential (1) in drug discovery where it enables simultaneously assessing therapeutic effect on target cells and toxic effect on non-target cells, and (2) in personalized adjuvant chemotherapy where multiple drugs can be tested in primary cultures derived from surgically removed tumor. PMID- 26558360 TI - Renal cell carcinoma: Review of etiology, pathophysiology and risk factors. AB - BACKGROUND AND AIMS: The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. METHODS: A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. RESULTS AND CONCLUSIONS: Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways. PMID- 26558361 TI - The critical points in induction of experimental autoimmune uveitis. AB - BACKGROUND: Autoimmune uveitis is a leading cause of visual impairment in developed countries in patients of working age. Animal models of experimental autoimmune uveitis (EAU) have been established to serve as a useful template for novel therapeutic approaches. METHODS: Experimental autoimmune uveitis is induced in C57BL/6 mice by subcutaneous application of interphotoreceptor retinoid binding protein in complete Freund's adjuvant and pertussis toxin. Clinical and histological grading is used to assess the inflammation intensity of EAU. RESULTS: The protocol of induction of EAU in mice hides several important aspects, which are crucial for developing the disease. These details have to be addressed to ensure reproducible disease induction. We describe our experience in establishing the model by pointing out the critical steps in EAU protocol which we found important. CONCLUSION: The mouse model of EAU has practical value for preclinical studies, is robust and well established. However, the induction of inflammation of the eye can be quite challenging when important details of the protocol are not recognized and adhered to. PMID- 26558362 TI - An Autopsy Case of Rapidly Progressing Spindle Cell Carcinoma of the Lung Accompanied with Intratumor Hemorrhage. AB - BACKGROUND: Spindle cell carcinoma (SPCC) of the lung is a subset of sarcomatoid carcinoma. Its clinical features are unclear because of its rarity. Here, we report an autopsy case of SPCC and review CT findings and chemotherapeutic regimens based on previous reports of this disease. To our knowledge, this is the first reported case of pemetrexed used to treat SPCC. CASE REPORT: A 74-year-old Japanese male presented with dyspnea and contrast-enhanced computed tomography (CT) showed abundant left pleural effusion and a mass in lower lobe of the left lung. By the tumor biopsy, he was diagnosed for SPCC of the lung, cT3N0M1a, stage IV. The tumor was resistant to chemotherapy with carboplatin and pemetrexed, and rapidly progressed. Autopsy revealed abundant hemorrhage within the tumor, which apparently reflects a low-density area in CT. CONCLUSIONS: Present case and the accumulation of cases indicate that low-density areas in CT and rapid tumor progression may be common SPCC findings. PMID- 26558363 TI - Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study. AB - BACKGROUND & AIMS: The population-based epidemiology of Budd-Chiari syndrome (BCS), a rare disease of hepatic venous outflow obstruction, is largely unknown. This study aimed to elucidate the nationwide population-based incidence, prevalence, complications, case fatalities and direct medical cost of BCS in South Korea from 2009 to 2013. METHODS: Using two large data sources, the Health Insurance Review and Assessment Service Claims database and Rare Intractable Disease registration program database in Korea, we identified all patients with BCS who were registered under International Classification of Diseases 10 (code I82.0). The age- and sex-adjusted incidence and prevalence of BCS were calculated with analysis of complications and direct medical costs. RESULTS: A total of 424 patients with BCS were identified in 2009-2013, with a female-to-male ratio of 1.8 and a median age of 51 years old. The average age- and sex-adjusted incidence from 2011 to 2013 was 0.87 per million per year, and the average age- and sex adjusted prevalence from 2009 to 2013 was 5.29 per million population. Among them, 10.3% accompanied liver cancer and 3.3% underwent liver transplantation. Annual case-fatality rate was 2.8%. Direct medical costs excluding uninsured services for BCS increased by year from 385 720 USD in 2009 to 765 983 USD in 2013. CONCLUSIONS: This is the first population-based study on the epidemiology of BCS in an Asian country, which presented a higher prevalence than in Western studies. It suggests early diagnosis or improved prognosis of BCS in recent years, and clinical features of BCS that differ by geography. PMID- 26558364 TI - Metamorphic thyroid autoimmunity in Down Syndrome: from Hashimoto's thyroiditis to Graves' disease and beyond. AB - BACKGROUND: It is known that Hashimoto's thyroiditis (HT) may progress to Graves' disease (GD) and that this phenomenon may be more frequent in the patients with Down syndrome (DS). AIMS: To shed light on the relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity. PATIENTS AND METHODS: We reconstructed the conversion process from HT to GD in 12 DS children. All the data recorded at HT diagnosis and throughout the time interval from entry to GD presentation were retrospectively taken from patients' files, as well as those recorded at GD diagnosis and during the subsequent evolution. From GD diagnosis all patients underwent methimazole treatment, at a dose that was adjusted on the basis of clinical findings and thyroid tests. RESULTS: Time interval between HT and GD was not different in the seven patients who received during that time a L thyroxine (L-T4) treatment than in those who were not treated. After methimazole onset all patients exhibited a prolonged remission of hyperthyroidism. In 8/12 patients this treatment is still being continued 2-7 years after its initiation. The mean methimazole dosage needed to maintain euthyroidism in these eight patients was 0.12 +/- 0.02 mg/kg/day. In the remaining four patients methimazole was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0-2.1 years after its withdrawal. These patients developed, 0.1-0.3 years after methimazole withdrawal, a picture of overt hypothyroidism and needed treatment with L-T4, that is now being continued. No patients needed non pharmacological therapies. CONCLUSIONS: 1) DS children might be incline to manifest over time a phenotypic metamorphosis from HT to GD and to subsequently fluctuate from hyperthyroidism to hypothyroidism; 2) in DS GD may have a mild biochemical and clinical course. PMID- 26558365 TI - Larval ecology of Anopheles coluzzii in Cape Coast, Ghana: water quality, nature of habitat and implication for larval control. AB - BACKGROUND: There is a growing interest in larval control intervention to supplement existing malaria control strategies, particularly in urban areas. However, effective implementation requires a good understanding of habitat ecology of Anopheles mosquitoes. Clean water bodies have long been reported by several studies as a preferred breeding habitat for Anopheles gambiae. Other studies have also reported the breeding of An. gambiae in polluted water bodies. However, the term clean or polluted is mostly based on visual examination and is not well defined. This study was conducted with the aim of assessing water quality in Anopheles breeding habitats and the practicability of larval control in Cape Coast, Ghana. METHODS: A larval survey was conducted for 15 months in Cape Coast. In individual breeding habitats, habitat characteristics, physicochemical parameters and bacterial fauna were measured in both Anopheles positive breeding (APL) habitats and habitats colonized by only Culex species. The sibling species of An. gambiae were identified using PCR assay. RESULTS: Anopheles coluzzii dominated in almost all the APL habitats found in this study. The habitats had high levels of salinity and ammonium ions. However, ammonium ions were significantly higher (p = 0.001) in habitats colonized by only Culex larvae compared to APL habitats. About 47 % of the habitats that were colonized by only Culex larvae had no measurable dissolved oxygen while An. coluzzii was absent in such habitats. High concentration of faecal bacteria confirmed faecal contamination in both groups of breeding habitats. CONCLUSIONS: From the results, it was evident that larval stages of An. coluzzii have tolerance to high levels of salinity and organic pollution in breeding habitats. However, its level of tolerance to organic pollution is probably lower than Culex larvae. The nature of breeding habitats found in the city demonstrates the opportunistic behaviour of An. coluzzii and how its breeding requirements are so intimately intertwined with the haphazard and uncontrolled human activities in the urban area. Considering the nature of APL habitats, larval control intervention could greatly reduce Anopheles population. However, improving basic hygiene and sanitation in the city could even make larval control intervention more practical and cost effective. PMID- 26558366 TI - A Multiplex Real-Time PCR Assay to Diagnose and Separate Helicoverpa armigera and H. zea (Lepidoptera: Noctuidae) in the New World. AB - The Old World bollworm, Helicoverpa armigera (Hubner), and the corn earworm, H. zea (Boddie), are two of the most important agricultural pests in the world. Diagnosing these two species is difficult-adults can only be separated with a complex dissection, and larvae cannot be identified to species using morphology, necessitating the use of geographic origin for identification in most instances. With the discovery of H. armigera in the New World, identification of immature Helicoverpa based on origin is no longer possible because H. zea also occurs in all of the geographic regions where H. armigera has been discovered. DNA barcoding and restriction fragment length polymorphism (RFLP) analyses have been reported in publications to distinguish these species, but these methods both require post-PCR processing (i.e., DNA sequencing or restriction digestion) to complete. We report the first real-time PCR assay to distinguish these pests based on two hydrolysis probes that bind to a segment of the internal transcribed spacer region 2 (ITS2) amplified using a single primer pair. One probe targets H. armigera, the second probe targets H. zea, and a third probe that targets a conserved segment of 18S rDNA is used as a control of DNA quality. The assay can be completed in 50 minutes when using isolated DNA and is successfully tested on larvae intercepted at ports of entry and adults captured during domestic surveys. We demonstrate that the assay can be run in triplex with no negative effects on sensitivity, can be run using alternative real-time PCR reagents and instruments, and does not cross react with other New World Heliothinae. PMID- 26558368 TI - Is the new GFR equation using inulin clearance a more accurate method for Asian patients? AB - Recently, a new glomerular filtration rate (GFR) equation for the Japanese population was proposed using measured inulin clearance. To expand its applicability to other Asian populations, we performed a comparative study in the Korean population. Inulin clearance was measured in 166 patients from seven participating medical centers in Korea. Patient's sera and urine were collected, and baseline clinical characteristics were measured to provide an estimated GFR (eGFR) by the Japanese GFR equation using inulin clearance (Japanese-GFR equation), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation. We compared the results to determine which equation best estimated the measured GFR (mGFR). Accuracy (95% CI) within 30% of mGFR by the Japanese-GFR equation, the CKD-EPI equation and the MDRD study equation were 66 (58 - 72), 51 (43 - 58), and 55 (47 - 62)%, respectively. Bias (mGFR minus eGFR) were 3.4 +/- 22.4, -12.0 +/- 22.1, and -9.7 +/- 23.8 mL/min/1.73 m2, respectively. The accuracy of the Japanese-GFR equation was significantly better than MDRD study equation in subjects with mGFR < 60 mL/min/1.73 m2 and in total subjects. The bias of the Japanese-GFR equation was significantly smaller compared with other two equations in total subjects. The Japanese-GFR equation has a higher accuracy with less bias than the other equations in estimating GFR in Korean populations. Further studies are required to determine if the current Japanese-GFR equation could represent the standard eGFR for other Asian populations. PMID- 26558367 TI - Reduced beta-amyloid pathology in an APP transgenic mouse model of Alzheimer's disease lacking functional B and T cells. AB - INTRODUCTION: In Alzheimer's disease, accumulation and pathological aggregation of amyloid beta-peptide is accompanied by the induction of complex immune responses, which have been attributed both beneficial and detrimental properties. Such responses implicate various cell types of the innate and adaptive arm of the immunesystem, both inside the central nervous system, and in the periphery. To investigate the role of the adaptive immune system in brain beta-amyloidosis, PSAPP transgenic mice, an established mouse model of Alzheimer's disease, were crossbred with the recombination activating gene-2 knockout (Rag2 ko) mice lacking functional B and T cells. In a second experimental paradigm, aged PSAPP mice were reconstituted with bone marrow cells from either Rag2 ko or wildtype control mice. RESULTS: Analyses from both experimental approaches revealed reduced beta-amyloid pathology and decreased brain amyloid beta-peptide levels in PSAPP mice lacking functional adaptive immune cells. The decrease in brain beta amyloid pathology was associated with enhanced microgliosis and increased phagocytosis of amyloid beta-peptide aggregates. CONCLUSION: The results of this study demonstrate an impact of the adaptive immunity on cerebral beta-amyloid pathology in vivo and suggest an influence on microglia-mediated amyloid beta peptide clearance as a possible underlying mechanism. PMID- 26558370 TI - Ertapenem-induced acute reversible peripheral neuropathy in chronic kidney disease: 3 case reports. AB - BACKGROUND: Ertapenem is a broad-spectrum and long-acting carbapenem which is predominantly eliminated by the kidneys, and it requires dose adjustment in renal failure. Although it is known that excessive doses of ertapenem can cause neurotoxicity, there are very few case reports of ertapenem-induced reversible peripheral neuropathy in the literature when used with renal adjusted doses. STUDY DESIGN AND METHODS: We report 3 patients with a history of stage 4 or 5 chronic kidney disease (CKD) who developed acute reversible peripheral neuropathy proven with electroencephalography (EEG) and electromyography (EMG). All patients received renal adjusted doses of ertapenem for complicated urinary tract infection (UTI). We also discuss the incidence of carbapenem-related neurotoxicity, mechanisms, and risk factors with a review of the literature. RESULTS: All patients developed acute peripheral, and additionally one acute central nervous system, neuropathy within 1 week of treatment with ertapenem, which was confirmed by EMG. Complete clinical recovery was obtained in all patients within 2 weeks of cessation of ertapenem treatment, and electromyography was confirmatory in all patients. CONCLUSION: Ertapenem is potentially neurotoxic in patients with CKD even when it is given with renal adjusted doses according to recommendations. Although carbapenem-related neurotoxicity most commonly manifests as seizures, our series indicates that acute and reversible peripheral neuropathy can also develop. Clinicians administering ertapenem for patients with a GFR of < 30 mL/min/1.73 m2 should be cautious. PMID- 26558371 TI - JASMS Transition. PMID- 26558369 TI - Associations of kidney injury markers with subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. PMID- 26558372 TI - Giant Gastric Liposarcoma: A Fatal Exceptional Location. PMID- 26558373 TI - Chemosensitization of Prostate Carcinoma Cells with a Receptor-directed Smac Conjugate. AB - BACKGROUND: Second mitochondrial activator of caspase (Smac) is a short mitochondrial peptide. When released from the mitochondria into the cytoplasm, it binds to inhibitor of apoptotic proteins (IAPs) within the cytoplasm and prevents them from inhibiting apoptosis. OBJECTIVE: Delivery of external synthetic Smac peptide into the cytoplasm of malignant cells could greatly improve the efficiency of apoptosis-inducing chemotherapeutic agents. METHOD: In our study different conjugates based on the seven N-terminal amino acids AVPIAQK of Smac (SmacN7) were produced to obtain a cytoplasm-directed Smac variant. SmacN7 and a point mutant (AVPKAQK) were coupled either to rhodamine alone or to both rhodamine and undecylic aldehyde, which is an antagonist of the Lily-of-the valley fragrance receptor. The fifth conjugate consisted of rhodamine coupled only to undecylic aldehyde, without SmacN7. The uptake of these five conjugates into three different human cell lines was characterized and quantified by confocal laser scanning microscopy and flow cytometry. A caspase apoptosis assay was performed for cells incubated with the five different conjugates after induction of apoptosis. RESULTS: The coupling of undecylic aldehyde to SmacN7 increased the cellular uptake of the correct and mutant conjugates. CONCLUSION: Caspase 3/7 apoptosis tests after induction of apoptosis with staurosporine or UV irradiation showed that the coupling of SmacN7 with undecylic aldehyde resulted in a greatly increased adjuvant pro-apoptotic effect compared to the separate components and a mutant SmacN7 peptide sequence in the LNCaP prostate carcinoma cells compared to the benign prostate hyperplasia (BPH) cells and the human embryonal kidney (HEK) cells. PMID- 26558374 TI - Synthesis, Structural Characterization of a Novel Ferrocene Derivative and Preliminarily Anticancer Activity. AB - A novel structure of ferrocene derivative 1 was synthesized with cyanuric chloride and ferrocenemethanol as starting materials. The synthesized compound was fully characterized using 1H NMR, 13C NMR, MS and XRD. Subsequently, the in vitro anticancer effect against A549, HCT116 and MCF-7 cell lines was preliminarily evaluated by the MTT method. The result showed that this compound exhibits good cytotoxic effect on A549, HCT116 and MCF-7 cell lines. PMID- 26558375 TI - Synthesis, Molecular Docking Study, and Cytotoxic Activity of 3,4-diaryl-5-(4 pyridinyl)-1,2,4-oxadiazole. AB - BACKGROUND: Triaryl oxadiazoles have been proven to be useful agents against various types of cancer cell lines. Nevertheless, their mechanism of action is not fully understood. OBJECTIVE: Synthesis and cytotoxic activity of a new group of triaryl oxadiazoles; 3,4-diaryl-5-(4- pyridinyl)-1,2,4-oxadiazole derivatives, will be discussed in this study. Their cytotoxic activity has been examined in 4 different cell lines by MTT method. METHOD: 3,4-Diaryl-5-(4-pyridinyl)-1,2,4 oxadiazole derivatives were prepared from condensation of different imines with 4 substituted benzohydroxyiminoyl chlorides. The antiproliferative activity of the final compounds was examined in MCF-7, AGS, HT-29 and NIH3T3 cell lines by MTT assay, using different concentrations of each compound to determine their IC50. The cytotoxic activity of paclitaxel, doxorubicin and combretastatin A-4 was evaluated as positive controls. RESULTS: All compounds demonstrated cytotoxic activity in mentioned cell lines, in a dose dependent manner. Among all, 6d-2 showed the highest cytotoxicity in AGS and MCF-7 cell lines with IC50 19.84 and 9.91 respectively and 6c-2 was the most potent in HT-29 with IC50 27.60. In addition, 6c-1, one of the most potent compounds, showed an interestingly low cytotoxic effect on NIH3T3 cell line, which is a noncancerous cell line. In the molecular modeling study, all compounds had comparable binding energy in Colchicine binding site and 6c-2 had the best-predicted binding energy. CONCLUSION: Together, our data suggest that the synthesized compounds have a partially selective mechanism of action against cancer cells and possibly a lower toxic effect on normal cells, making them interesting candidates for the synthesis of new anticancer agents. PMID- 26558376 TI - Design, Synthesis, and Fungicidal Activities of Novel 5-Methyl-1H-1,2,3- trizole 4-carboxyl Amide Analogues. AB - Succinate dehydrogenase inhibitors (SDHIs) are fungicides with an amide bond widely used to control plant diseases caused by phytopathogenic fungi. Because of broad spectrum activity of new SDHIs, they have attracted wide attention from the research community. A series of structurally novel SDHIs with a bioactive 1,2,3 triazole moiety were designed and synthesized. Bioactivity screening showed that some of designed N-phenethyl-1,2,3-trizole-4-carboxyl amide analogues exhibited good fungicidal activities toward Sclerotinia sclerotiorum and Botrytis cinerea, while some of Nbenzyl- 1,2,3-trizole-4-carboxyl amide analogues exhibited good fungicidal activities toward Phytophthora capsici and Cercospora arachidicola. EC50 value of compound 5d against Cercospora arachidicola (6.6 ug/mL) was lower than that of chlorothalonil (12.3 ug/mL). PMID- 26558377 TI - DNA Hybridization on Chitosan-Functionalized Silicon Substrate. AB - The ability of DNA to capture oligonucleotide molecules in solution is of great importance in genetics, medical diagnostics, and drug discovery. The DNA hybridization event in which the probe, which is usually a single-stranded DNA (ssDNA) covalently immobilized on a functionalized surface, recognizes the complementary target and forms a stable duplex structure that is the basis of highly specific bio recognizing devices. In this computational study, molecular modeling and Quantitative Structure Activity Relationship (QSAR) calculations were utilized at PM3 level in order to evaluate the interaction of aldehyde ssDNA on chitosan-functionalized silicon substrate and the biological activity of the proposed compounds. Molecular modeling of ssDNA 5'-(TTCA) attached on chitosan- functionalized silicon dioxide substrate was carried out. Molecular modeling and QSAR calculations were utilized at MM3 level in order to evaluate the interaction of target DNA on DNA probe on chitosan-functionalized silicon substrate through hydrogen bonding and the biological activity of the proposed compounds. PMID- 26558378 TI - Bone remodeling markers: so easy to measure, so difficult to interpret. PMID- 26558379 TI - Bone turnover markers: response to comments by Seeman and Nguyen. PMID- 26558380 TI - Assessment of off-label use of denosumab 60 mg injection during the early postmarketing period using health insurance claims data. AB - Off-label use of denosumab 60 milligram (mg) injection was assessed within an administrative claims database. The completeness of claims to assess off-label use was investigated with medical record review. Potential denosumab 60 mg off label use was observed based on claims, but many had evidence of on-label indications based on medical record review. INTRODUCTION: Denosumab 60 mg injection is approved in the USA to treat patients at high fracture risk due to postmenopausal osteoporosis, male osteoporosis, and hormone therapy for the treatment of prostate and breast cancers. Its RANK ligand-inhibiting effect makes it a candidate for the off-label treatment of other conditions mediated by the rate of bone resorption by osteoclasts. To better understand its utilization patterns, we assessed off-label use of denosumab 60 mg within an administrative claims database. METHODS: Definite, probable, and possible denosumab 60 mg users were identified during the early postmarketing period within a claims database of a US healthcare insurer. Medical record review confirmed a sample of these users. Off-label use among definite and probable users and all chart-confirmed users was classified using claims-derived age, dose interval, and diagnosis and treatment received relative to the administration date. Among chart-confirmed users classified as off-label, patient characteristics related to treatment indication were abstracted from medical records to investigate the completeness of claims to study off-label medication use. RESULTS: Off-label use was identified based on claims in approximately 25 % of definite and probable denosumab 60 mg users and 35 % of chart-confirmed users. Medical record review identified evidence of on label indications in 81 % of chart-confirmed users classified as off-label in claims. CONCLUSIONS: Many of the off-label denosumab 60 mg users had diagnoses or treatment consistent with on-label indications based on medical record review, suggesting these are under-recorded in claims data. It is warranted to be cautious when using administrative databases to assess off-label medication use. PMID- 26558381 TI - Salmonella enterica Serovar Napoli Infection in Italy from 2000 to 2013: Spatial and Spatio-Temporal Analysis of Cases Distribution and the Effect of Human and Animal Density on the Risk of Infection. AB - BACKGROUND: Salmonella Napoli is uncommon in Europe. In Italy however, it has been growing in importance since 2000. To date, no risk factors have been identified to account for its rise. This study aims at describing the epidemiology, spatial and spatio-temporal patterns of S. Napoli in Italy from 2000 to 2013, and to explore the role of several environmental correlates, namely urbanization, altitude and number of livestock farms, on the risk of S. Napoli infection among humans. METHOD: Data were obtained from Enter-Net Italy, a network of diagnostic laboratories. The data were aggregated at the municipality level. Descriptive epidemiology, multivariate regression models, spatial and spatio-temporal analyses were performed on the number of cases and incidence rates. RESULTS: S. Napoli showed an expanding trend at the national level, and an increasing number of cases. Compared to the other main serovars in Italy, the risk of S. Napoli infection was higher in the age group <1 year, and lower in the other age groups. Although urbanization and the number of farms were associated with the risk of S. Napoli infection to some extent, their role in the epidemiology of the disease remains inconclusive. S. Napoli cases showed a positive global spatial autocorrelation as well as a significant spatio-temporal interaction. Twenty-four spatial and spatio-temporal clusters were identified, seven purely spatial and 17 spatio-temporal, mainly in north-western Italy. Most of the clusters were in areas characterized by urban and industrial settlements surrounded by agricultural land and an abundance of freshwater bodies. CONCLUSIONS: Our results point to the presence, in a number of areas in Italy, of a Salmonella of public health concern originating in the environment. This highlights the increasing relevance of environmental, non-food-related sources of human exposure to enteric pathogens. PMID- 26558383 TI - MicroRNA in ovarian function. AB - The mammalian ovary is a dynamic organ. The coordination of follicle recruitment, selection, and ovulation and the timely development and regression of the corpus luteum are essential for a functional ovary and fertility. Deregulation of any of these processes results in ovarian dysfunction and potential infertility. MicroRNA (miRNA) are short noncoding RNA that regulate developmental processes and time-sensitive functions. The expression of miRNA in the ovary varies with cell type, function, and stage of the estrous cycle. miRNA are involved in the formation of primordial follicles, follicular recruitment and selection, follicular atresia, oocyte-cumulus cell interaction, granulosal cell function, and luteinization. miRNA are differentially expressed in luteal cells at the various stages of the estrous cycle and during maternal recognition of pregnancy, suggesting a role in luteal development, maintenance, and regression. An understanding of the patterns of expression and functions of miRNA in the ovary will lead to novel therapeutics to treat ovarian dysfunction and improve fertility and, potentially, to the development of better contraceptives. PMID- 26558384 TI - Proteasome Inhibition Diminishes the Formation of Neutrophil Extracellular Traps and Prevents the Death of Cardiomyocytes in Coculture with Activated Neutrophils during Anoxia-Reoxygenation. AB - OBJECTIVE: Polymorphic mononuclear neutrophils (PMN) are very important cells participating in nonspecific defense of the organism. Among their well-known functions, the formation of neutrophil extracellular traps (NET) is interesting and potentially dangerous for the mechanisms of other cells. Ubiquitin-dependent proteasomal proteolysis is a very important regulator of all cellular activities, but the role of proteasomal proteolysis in NET formation has not been investigated. METHODS: We performed experiments with PMN activated to form NET with phorbol 12-myristate 13-acetate (PMA) and the application of a proteasome inhibitor. We also added activated neutrophils to primary culture of isolated rat neonatal cardiomyocytes with or without anoxia-reoxygenation modeling. RESULTS: The data obtained show that proteasomes participate in NET formation and proteasome inhibitors facilitate the blocking of the NET program. The percentage of NET after PMA application was 70.8 +/- 7.2 and the proteasome inhibitor decreased this amount to 4.7 +/- 0.9%. In coculture with cardiomyocytes during anoxia-reoxygenation, this effect prevented cardiac cell death induced by activated PMN. The stimulation of NET formation by PMA in coculture with isolated cardiomyocytes led to an increase in the number of necrotic cardiomyocytes of up to 33.1 +/- 12.9% and a corresponding decrease in living cardiomyocytes to 66.9 +/- 12.9%. The number of living cardiomyocytes in coculture after incubation with both PMA and proteasome inhibitor was 76.6 +/- 13.3% (p < 0.05), and the number of necrotic cardiomyocytes was 23.4 +/- 13.3% (p < 0.05). CONCLUSION: Proteasome inhibition blocks NET formation and prevents cardiomyocyte necrosis in coculture with activated neutrophils. PMID- 26558385 TI - Differentiated Anti-Predation Responses in a Superorganism. AB - Insect societies are complex systems, displaying emergent properties much greater than the sum of their individual parts. As such, the concept of these societies as single 'superorganisms' is widely applied to describe their organisation and biology. Here, we test the applicability of this concept to the response of social insect colonies to predation during a vulnerable period of their life history. We used the model system of house-hunting behaviour in the ant Temnothorax albipennis. We show that removing individuals from directly within the nest causes an evacuation response, while removing ants at the periphery of scouting activity causes the colony to withdraw back into the nest. This suggests that colonies react differentially, but in a coordinated fashion, to these differing types of predation. Our findings lend support to the superorganism concept, as the whole society reacts much like a single organism would in response to attacks on different parts of its body. The implication of this is that a collective reaction to the location of worker loss within insect colonies is key to avoiding further harm, much in the same way that the nervous systems of individuals facilitate the avoidance of localised damage. PMID- 26558386 TI - Synergistic effect of combined transcranial direct current stimulation/constraint induced movement therapy in children and young adults with hemiparesis: study protocol. AB - BACKGROUND: Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. METHODS/DESIGN: A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. DISCUSSION: Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02250092 Registered 18 September 2014. PMID- 26558387 TI - PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas. AB - Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR) based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas. PMID- 26558389 TI - Customizable 3D Printed 'Plug and Play' Millifluidic Devices for Programmable Fluidics. AB - Three dimensional (3D) printing is actively sought after in recent years as a promising novel technology to construct complex objects, which scope spans from nano- to over millimeter scale. Previously we utilized Fused deposition modeling (FDM)-based 3D printer to construct complex 3D chemical fluidic systems, and here we demonstrate the construction of 3D milli-fluidic structures for programmable liquid handling and control of biological samples. Basic fluidic operation devices, such as water-in-oil (W/O) droplet generators for producing compartmentalized mono-disperse droplets, sensor-integrated chamber for online monitoring of cellular growth, are presented. In addition, chemical surface treatment techniques are used to construct valve-based flow selector for liquid flow control and inter-connectable modular devices for networking fluidic parts. As such this work paves the way for complex operations, such as mixing, flow control, and monitoring of reaction / cell culture progress can be carried out by constructing both passive and active components in 3D printed structures, which designs can be shared online so that anyone with 3D printers can reproduce them by themselves. PMID- 26558388 TI - Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex. AB - Calcium-activated chloride channels of the anoctamin (alias TMEM16) protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum. PMID- 26558390 TI - Estimating Toronto's health services use for the 2015 Pan American and Parapan American Games. AB - AIMS: Ambient air temperature may exacerbate the burden of chronic diseases on Ontario's healthcare system during mass gathering events. This study aimed to estimate the impact of increasing temperature in July and August on health services use for chronic conditions in Ontario's Golden Horseshoe region during the 2015 Pan American and Parapan American Games, using environmental and health administrative data from previous years. METHOD: Negative binomial regression was used to calculate incidence risk ratios for same-day health services use (hospitalisations, emergency department visits, physician office visits) for all causes, asthma, asthma-related conditions, diabetes and hypertension associated with unit increases in daily maximum temperature from 1 May to 31 August in 2008 2010. Sensitivity analysis was performed to estimate the added burden of an increased population size, in order to model an influx of visitors during the Games. RESULTS: In July and August, on days with daily maximum temperatures of 35 degrees C compared to 25 degrees C, we estimated seeing 7,827 more physician office visits for all causes in Ontario's Golden Horseshoe region. The estimated relative increase in physician office visits for diabetes due to temperature alone was 8.4%. With an estimated 10% increase in population, the increase in physician office visits for all causes tripled to an estimated 23,590. CONCLUSION: Temperature was identified as a potential contributor to greater health services use during the Games, particularly for those living with diabetes. These results highlight the importance of strategic delivery of health services during mass gathering events, and suggest a role for educating at-risk individuals on prevention behaviours, particularly on very hot days. PMID- 26558391 TI - 99mTc-HYNIC-TOC increased uptake can mimic malignancy in the pancreas uncinate process at somatostatin receptor SPECT/CT. AB - OBJECTIVE: The aim of this study was to assess the occurrence and frequency of increased physiologic uptake of 99mTc-HYNIC-TOC by the uncinate process of the pancreas in SPECT/CT images. METHODS: Forty-six scans of 41 patients were evaluated retrospectively. The uptake of 99mTc-HYNIC-TOC was considered to be physiologic in patients with normal findings at dedicated abdominal CT or MR and lack of neoplastic lesions in clinical follow-ups. The intensity of uncinate process uptake was compared to the uptake of the normal liver. RESULTS: Focal uptake was attributed to the presence of pancreatic NET in 5 patients. Among the 36 patients without any evidence of malignancy in CT, MR and follow-up, 7 (19.4 %) showed increased uptake in the uncinate process. The intensity of uptake was lesser in 3 (8.3 %), similar in 3 and greater than the normal liver in 1 (2.8 %) case. CONCLUSION: Increased 99mTc-HYNIC-TOC uptake occurred in 19.4 % of those subjects without any evidence of neuroendocrine tumor in the uncinate process. PMID- 26558392 TI - Wales's proposed opt out organ donation system. PMID- 26558393 TI - The Predictive Factors on Extended Hospital Length of Stay in Patients with AMI: Laboratory and Administrative Data. AB - The length of hospital stay (LOS) is an important measure of efficiency in the use of hospital resources. Acute Myocardial Infarction (AMI), as one of the diseases with higher mortality and LOS variability in the OECD countries, has been studied with predominant use of administrative data, particularly on mortality risk adjustment, failing investigation in the resource planning and specifically in LOS. This paper presents results of a predictive model for extended LOS (LOSE - above 75th percentile of LOS) using both administrative and clinical data, namely laboratory data, in order to develop a decision support system. Laboratory and administrative data of a Portuguese hospital were included, using logistic regression to develop this predictive model. A model with three laboratory data and seven administrative data variables (six comorbidities and age >= 69 years), with excellent discriminative ability and a good calibration, was obtained. The model validation shows also good results. Comorbidities were relevant predictors, mainly diabetes with complications, showing the highest odds of LOSE (OR = 37,83; p = 0,001). AMI patients with comorbidities (diabetes with complications, cerebrovascular disease, shock, respiratory infections, pulmonary oedema), with pO2 above level, aged 69 years or older, with cardiac dysrhythmia, neutrophils above level, pO2 below level, and prothrombin time above level, showed increased risk of extended LOS. Our findings are consistent with studies that refer these variables as predictors of increased risk. PMID- 26558394 TI - Assessing the Queuing Process Using Data Envelopment Analysis: an Application in Health Centres. AB - Queuing is one of the very important criteria for assessing the performance and efficiency of any service industry, including healthcare. Data Envelopment Analysis (DEA) is one of the most widely-used techniques for performance measurement in healthcare. However, no queue management application has been reported in the health-related DEA literature. Most of the studies regarding patient flow systems had the objective of improving an already existing Appointment System. The current study presents a novel application of DEA for assessing the queuing process at an Outpatients' department of a large public hospital in a developing country where appointment systems do not exist. The main aim of the current study is to demonstrate the usefulness of DEA modelling in the evaluation of a queue system. The patient flow pathway considered for this study consists of two stages; consultation with a doctor and pharmacy. The DEA results indicated that waiting times and other related queuing variables included need considerable minimisation at both stages. PMID- 26558395 TI - Smart ECG Monitoring Patch with Built-in R-Peak Detection for Long-Term HRV Analysis. AB - Since heart rate variability (HRV) analysis is widely used to evaluate the physiological status of the human body, devices specifically designed for such applications are needed. To this end, we developed a smart electrocardiography (ECG) patch. The smart patch measures ECG using three electrodes integrated into the patch, filters the measured signals to minimize noise, performs analog-to digital conversion, and detects R-peaks. The measured raw ECG data and the interval between the detected R-peaks can be recorded to enable long-term HRV analysis. Experiments were performed to evaluate the performance of the built-in R-wave detection, robustness of the device under motion, and applicability to the evaluation of mental stress. The R-peak detection results obtained with the device exhibited a sensitivity of 99.29%, a positive predictive value of 100.00%, and an error of 0.71%. The device also exhibited less motional noise than conventional ECG recording, being stable up to a walking speed of 5 km/h. When applied to mental stress analysis, the device evaluated the variation in HRV parameters in the same way as a normal ECG, with very little difference. This device can help users better understand their state of health and provide physicians with more reliable data for objective diagnosis. PMID- 26558396 TI - HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy. AB - INTRODUCTION: We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naive individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. METHODS: 365 HIV-infected, ART naive, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm. RESULTS: PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p<0.0001). No significant trends in time were observed when comparing 2013 and 2014, when using a moving average approach along the study period or when comparing individuals with >500 vs. <350 CD4+ T cells/MUL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the >=48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naive individuals and between ART-naive individuals. CONCLUSIONS: The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations. PMID- 26558397 TI - Deaf Students' Reading and Writing in College: Fluency, Coherence, and Comprehension. AB - Research in discourse reveals numerous cognitive connections between reading and writing. Rather than one being the inverse of the other, there are parallels and interactions between them. To understand the variables and possible connections in the reading and writing of adult deaf students, we manipulated writing conditions and reading texts. First, to test the hypothesis that a fluent writing process leads to richer content and a higher degree of coherence in a written summary, we interrupted the writing process with verbal and nonverbal intervening tasks. The negligible effect of the interference indicated that the stimuli texts were not equivalent in terms of coherence and revealed a relationship between coherence of the stimuli texts, amount of content recalled, and coherence of the written summaries. To test for a possible effect of coherence on reading comprehension, we manipulated the coherence of the texts. We found that students understood the more coherent versions of the passages better than the less coherent versions and were able to accurately distinguish between them. However, they were not able to judge comprehensibility. Implications for further research and classroom application are discussed. PMID- 26558399 TI - Appropriate Level of Low-Density Lipoprotein Cholesterol for Secondary Prevention of Coronary Artery Disease. AB - AIM: Current Japanese guidelines state the target level of low-density lipoprotein cholesterol (LDL-C) of <100mg/dL for secondary prevention of coronary artery disease (CAD). However, this level was set considering the results of trials mainly conducted in Western countries. In addition, the effect of achieving target LDL-C on secondary prevention is unknown. METHODS: We examined the effects of achieving target LDL-C on clinical outcomes. Patients who underwent percutaneous coronary intervention at Juntendo University Hospital (Tokyo, Japan) from 2004 to 2010 and received follow-up coronary angiography (CAG) were analyzed. The study population was divided into two groups based on the follow-up LDL-C. The incidence of major adverse cardiovascular events within 3 years after the follow-up CAG was examined. RESULTS: A total of 1321 consecutive patients were enrolled. Sixty-three percent of the patients achieved the target LDL-C. The rate of 3-year events was lower in the group that achieved the target LDL-C (achieved group). The adjusted relative risk reduction in the achieved group was 26% (p=0.02). In the sub-analysis among the four groups stratified by baseline LDL-C of 140 and follow-up LDL-C of 100, the adjusted hazard ratio for 3-year events was 1.84 (95% confidence interval; 1.10-3.24)in Group 3 (baseline <140, follow-up >=100) and 2.05 (1.18-3.74) Group 4 (baseline >=140, follow-up >=100) [Group 2 (baseline >=140, follow-up <100) as reference]. CONCLUSIONS: Our data suggested that follow-up LDL-C <100mg/dL was appropriate for secondary prevention of CAD in Japanese population. PMID- 26558400 TI - Thyroid Hormone and Vascular Remodeling. AB - Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID- 26558401 TI - Brachial-Ankle PWV: Current Status and Future Directions as a Useful Marker in the Management of Cardiovascular Disease and/or Cardiovascular Risk Factors. AB - Since 2001, brachial-ankle pulse wave velocity (brachial-ankle PWV) measurement has been applied for risk stratification of patients with atherosclerotic cardiovascular disease and/or its risk factors in Japan. Measurement of the brachial-ankle PWV is simple and well standardized, and its reproducibility and accuracy are acceptable. Several cross-sectional studies have demonstrated a significant correlation between the brachial-ankle PWV and known risk factors for cardiovascular disease; the correlation is stronger in subjects with cardiovascular disease than in those without cardiovascular disease. We conducted a meta-analysis, which demonstrated that the brachial-ankle PWV is an independent predictor of future cardiovascular events. Furthermore, the treatment of cardiovascular risk factors and lifestyle modifications have been shown to improve the brachial-ankle PWV. Thus, at present, brachial-ankle PWV is close to being considered as a useful marker in the management of atherosclerotic cardiovascular disease and/or its risk factors. PMID- 26558402 TI - Physiological Assessment in Peripheral Artery Disease: Going Beyond Angiography. PMID- 26558398 TI - Genetic control of root growth: from genes to networks. AB - BACKGROUND: Roots are essential organs for higher plants. They provide the plant with nutrients and water, anchor the plant in the soil, and can serve as energy storage organs. One remarkable feature of roots is that they are able to adjust their growth to changing environments. This adjustment is possible through mechanisms that modulate a diverse set of root traits such as growth rate, diameter, growth direction and lateral root formation. The basis of these traits and their modulation are at the cellular level, where a multitude of genes and gene networks precisely regulate development in time and space and tune it to environmental conditions. SCOPE: This review first describes the root system and then presents fundamental work that has shed light on the basic regulatory principles of root growth and development. It then considers emerging complexities and how they have been addressed using systems-biology approaches, and then describes and argues for a systems-genetics approach. For reasons of simplicity and conciseness, this review is mostly limited to work from the model plant Arabidopsis thaliana, in which much of the research in root growth regulation at the molecular level has been conducted. CONCLUSIONS: While forward genetic approaches have identified key regulators and genetic pathways, systems biology approaches have been successful in shedding light on complex biological processes, for instance molecular mechanisms involving the quantitative interaction of several molecular components, or the interaction of large numbers of genes. However, there are significant limitations in many of these methods for capturing dynamic processes, as well as relating these processes to genotypic and phenotypic variation. The emerging field of systems genetics promises to overcome some of these limitations by linking genotypes to complex phenotypic and molecular data using approaches from different fields, such as genetics, genomics, systems biology and phenomics. PMID- 26558403 TI - The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice. AB - The mechanisms responsible for the evolution of steatosis towards NASH (non alcoholic steatohepatitis) and fibrosis are not completely defined. In the present study we evaluated the role of CD4(+) T-helper (Th) cells in this process. We analysed the infiltration of different subsets of CD4(+) Th cells in C57BL/6 mice fed on a MCD (methionine choline-deficient) diet, which is a model reproducing all phases of human NASH progression. There was an increase in Th17 cells at the beginning of NASH development and at the NASH-fibrosis transition, whereas levels of Th22 cells peaked between the first and the second expansion of Th17 cells. An increase in the production of IL (interleukin)-6, TNFalpha (tumour necrosis factor alpha), TGFbeta (transforming growth factor beta) and CCL20 (CC chemokine ligand 20) accompanied the changes in Th17/Th22 cells. Livers of IL-17( /-) mice were protected from NASH development and characterized by an extensive infiltration of Th22 cells. In vitro, IL-17 exacerbated the JNK (c-Jun N-terminal kinase)-dependent mouse hepatocyte lipotoxicity induced by palmitate. IL-22 prevented lipotoxicity through PI3K (phosphoinositide 3-kinase)-mediated inhibition of JNK, but did not play a protective role in the presence of IL-17, which up-regulated the PI3K/Akt inhibitor PTEN (phosphatase and tensin homologue deleted on chromosome 10). Consistently, livers of IL-17(-/-) mice fed on the MCD diet displayed decreased activation of JNK, reduced expression of PTEN and increased phosphorylation of Akt compared with livers of wild-type mice. Hepatic infiltration of Th17 cells is critical for NASH initiation and development of fibrosis in mice, and reflects an infiltration of Th22 cells. Th22 cells are protective in NASH, but only in the absence of IL-17. These data strongly support the potentiality of clinical applications of IL-17 inhibitors that can prevent NASH by both abolishing the lipotoxic action of IL-17 and allowing IL-22-mediated protection. PMID- 26558404 TI - Perspectives on the viscoelasticity and flow behavior of entangled linear and branched polymers. AB - We briefly review the recent advances in the rheology of entangled polymers and identify emerging research trends and outstanding challenges, especially with respect to branched polymers. Emphasis is placed on the role of well characterized model systems, as well as the synergy of synthesis characterization, rheometry and modeling/simulations. The theoretical framework for understanding the observed linear and nonlinear rheological phenomena is the tube model, which is critically assessed in view of its successes and shortcomings, and alternative approaches are briefly discussed. Finally, intriguing experimental findings and controversial issues that merit consistent explanation, such as shear banding instabilities, multiple stress overshoots in transient simple shear and enhanced steady-state elongational viscosity in polymer solutions, are discussed, and future directions such as branch point dynamics and anisotropic monomeric friction are outlined. PMID- 26558405 TI - Flavoalkaloids and Flavonoids from Astragalus monspessulanus. AB - A new flavonol tetraglycoside, quercetin-3-O-[alpha-L-rhamnopyranosyl-(1->2) [alpha-L-rhamnopyranosyl-(1->6)]-beta-D-galactopyranosyl]-7-O-beta-D glucopyranoside (1), and two new flavonol alkaloids, N-(8-methylquercetin-3-O [alpha-L-rhamnopyranosyl-(1->2)-[alpha-L-rhamnopyranosyl-(1->6)]-beta-D galactopyranosyl])-3-hydroxypiperidin-2-one (2) and N-(8-methylkaempferol-3-O [alpha-L-rhamnopyranosyl-(1->2)-[alpha-L-rhamnopyranosyl-(1->6)]-beta-D galactopyranosyl])-3-hydroxypiperidin-2-one (3), were isolated from the aerial parts of Astragalus monspessulanus ssp. monspessulanus. Two rare flavonoids with an unusual 3-hydroxy-3-methylglutaric acid moiety, quercetin-3-O-alpha-L rhamnopyranosyl-(1->2)-[6-O-(3-hydroxy-3-methylglutaryl)-beta-D-galactopyranoside (4) and kaempferol-3-O-alpha-L-rhamnopyranosyl-(1->2)-[6-O-(3-hydroxy-3 methylglutaryl)-beta-D-galactopyranoside (5), were isolated from the aerial parts of A. monspessulanus ssp. illyricus. In addition, the eight known flavonoids alangiflavoside (6), alcesefoliside (7), mauritianin (8), quercetin-3-beta robinobioside (9), cosmosine (10), apigenin-4'-O-glucoside (11), trifolin (12), and rutin (13) were isolated from aerial parts of A. monspessulanus ssp. monspessulanus. Their structures were elucidated via NMR and HRESIMS data. In a model that tested t-BuOOH-induced oxidative stress on isolated rat hepatocytes, flavonoids 1-13 had statistically significant cytoprotective activity similar to that of silymarin, tested at 60 MUg/mL. The most prominent effects were observed for flavonoids 1, 4, 7, and 12. PMID- 26558406 TI - Digermylene Oxide Stabilized Group 11 Metal Iodide Complexes. AB - Use of a substituted digermylene oxide as a ligand has been demonstrated through the isolation of a series of group 11 metal(I) iodide complexes. Accordingly, the reactions of digermylene oxide [{(i-Bu)2ATIGe}2O] (ATI = aminotroponiminate) (1) with CuI under different conditions afforded [({(i-Bu)2ATIGe}2O)2(Cu4I4)] (2) with a Cu4I4 octahedral core, [({(i-Bu)2ATIGe}2O)2(Cu3I3)] (3) with a Cu3I3 core, and [{(i-Bu)2ATIGe}2O(Cu2I2)(C5H5N)2] (4) with a butterfly-type Cu2I2 core. The reactions of compound 1 with AgI and AuI produced [({(i-Bu)2ATIGe}2O)2(Ag4I4)] (5) with a Ag4I4 octahedral core and [{(i-Bu)2ATIGe}2O(Au2I2)] (6) with a Au2I2 core, respectively. The presence of metallophilic interactions in these compounds is shown through the single-crystal X-ray diffraction and atom-in-molecule (AIM) studies. Preliminary photophysical studies on compound 6 are also carried out. PMID- 26558407 TI - How will new and future therapies change our treatment of IBD? AB - Fundamental insights into the pathogenesis of inflammatory bowel diseases (IBD) have led to the development of new therapies and lots of experimental compounds in the pipeline. Our treatment of IBD is therefore constantly evolving. In this editorial, we postulate that bi- or even polyspecific therapy will be an important mainstay of future IBD treatment. Moreover, we highlight some promising new therapeutic concepts currently under investigation and point at the outstanding and growing importance of personalized medicine to assign drugs from the increasing pool of options to the individual patient. PMID- 26558408 TI - General Homologation Strategy for Synthesis of L-glycero- and D-glycero Heptopyranoses. AB - A general and stereospecific homologation strategy for the synthesis of heptopyranosides is reported. The strategy employs the Wittig olefination and proline-catalyzed alpha-aminoxylation to achieve one carbon elongation and stereoselective hydroxylation at the C6 position, respectively. The L-glycero- and D-glycero-heptopyranosides can be obtained with nearly perfect stereoselectivity. Further study reveals the difference in the chemical shift of the C6 proton of L/D-glycero-heptopyranosyl diastereomers, which is found to be useful for assignment of the configuration of heptopyranosides. PMID- 26558409 TI - Magnetic Separation-Assistant Fluorescence Resonance Energy Transfer Inhibition for Highly Sensitive Probing of Nucleolin. AB - For the widely used "off-on" fluorescence (or phosphorescence) resonance energy transfer (FRET or PRET) system, the separation of donors and acceptors species was vital for enhancing the sensitivity. To date, separation of free donors from FRET/PRET inhibition systems was somewhat not convenient, whereas separation of the target-induced far-between acceptors has hardly been reported yet. We presented here a novel magnetic separation-assistant fluorescence resonance energy transfer (MS-FRET) inhibition strategy for highly sensitive detection of nucleolin using Cy5.5-AS1411 as the donor and Fe3O4-polypyrrole core-shell (Fe3O4@PPY) nanoparticles as the NIR quenching acceptor. Due to hydrophobic interaction and pi-pi stacking of AS1411 and PPY, Cy5.5-AS1411 was bound onto the surface of Fe3O4@PPY, resulting in 90% of fluorescence quenching of Cy5.5-AS1411. Owing to the much stronger specific interaction of AS1411 and nucleolin, the presence of nucleolin could take Cy5.5-AS1411 apart from Fe3O4@PPY and restore the fluorescence of Cy5.5-AS1411. The superparamagnetism of Fe3O4@PPY enabled all separations and fluorescence measurements complete in the same quartz cell, and thus allowed the convenient but accurate comparison of the sensitivity and fluorescence recovery in the cases of separation or nonseparation. Compared to nonseparation FRET inhibition, the separation of free Cy5.5-AS1411 from Cy5.5 AS1411-Fe3O4@PPY solution (the first magnetic separation, MS-1) had as high as 25 fold enhancement of the sensitivity, whereas further separation of the nucleolin inducing far-between Fe3O4@PPY from the FRET inhibition solution (the second magnetic separation, MS-2) could further enhance the sensitivity to 35-fold. Finally, the MS-FRET inhibition assay displayed the linear range of 0.625-27.5 MUg L(-1) (8.1-359 pM) and detection limit of 0.04 MUg L(-1) (0.05 pM) of nucleolin. The fluorescence intensity recovery (the percentage ratio of the final restoring fluorescence intensity to the quenched fluorescence intensity of Cy5.5 AS1411 solution by 0.09 g L(-1) Fe3O4@PPY) was enhanced from 36% (for nonseparation) to 56% (for two magnetic separations). This is the first accurate evaluation for the effect of separating donor/acceptor species on the FRET inhibition assay. PMID- 26558410 TI - 3D Micropatterned Surface Inspired by Salvinia molesta via Direct Laser Lithography. AB - Biomimetic functional surfaces are attracting increasing attention for their relevant technological applications. Despite these efforts, inherent limitations of microfabrication techniques prevent the replication of complex hierarchical microstructures. Using a 3D laser lithography technique, we fabricated a 3D patterned surface bioinspired to Salvinia molesta leaves. The artificial hairs, with crownlike heads, were reproduced by scaling down (ca. 100 times smaller) the dimensions of natural features, so that microscale hairs with submicrometric resolution were attained. The micropatterned surface, in analogy with the natural model, shows interesting properties in terms of hydrophobicity and air retention when submerged by water, even if realized with a hydrophilic material. Furthermore, we successfully demonstrated the capability to promote localized condensation of water droplets from moisture in the atmosphere. PMID- 26558411 TI - A review of animal models of obsessive-compulsive disorder: a focus on developmental, immune, endocrine and behavioral models. AB - INTRODUCTION: Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by intrusive thoughts (obsessions) and/or repetitive behaviors (compulsions). Several models of OCD exist, many which employ behaviors such as over-grooming or hoarding as correlates for compulsive behaviors - often using a response to serotonergic agents as evidence for their validity. Recent discoveries in the genetics of OCD and the identification of aberrancies of glutamatergic, hormonal, and immune pathways in the OCD phenotype highlight a need to review existing of animal models of OCD. The focus of attention to these pathways may lead to possible new targets for drug discovery. AREAS COVERED: In this review, the authors describe frameworks for animal models in OCD conceptualized as either biological (e.g., developmental, genetic, and endocrine pathways), or behavioral (e.g., repetitive grooming, and stereotypies). In addition, the authors give special attention to the emerging role of glutamate in OCD. EXPERT OPINION: While many animal models for OCD demonstrate pathologic repetitive behavior phenotypes, which are relieved by serotoninergic agents, animal models based on reversal learning, perseverative responding, and neurodevelopmental mechanisms represent robust new paradigms. Glutamatergic influences in these new animal models suggest that drug discovery using neuroprotective approaches may represent a new stage for pharmacologic developments in OCD. PMID- 26558412 TI - Clinical features and Staphylococcus aureus colonization/infection in childhood atopic dermatitis. AB - INTRODUCTION: Staphylococcus aureus (SA) colonization/infection is important in the pathophysiology of childhood atopic dermatitis (AD). This study evaluated which clinical features may predict presence of SA colonization/infection and reviewed antimicrobial sensitivity of SA in patients with AD. METHODS: The associations between bacteriologic culture results of skin swabs (taken at the most severely affected area and at the antecubital fossa) and SCORing-Atopic Dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and quality of life were evaluated. RESULTS: Moderate-to-heavy growth of SA was present in 31% of the swabs of the most severe area and in 16% of the flexural (antecubital fossae) areas of 95 AD patients (12.5 +/- 4.8 years). Binomial logistic regression showed moderate-to-heavy growth of SA in the severe area were associated with objective SCORAD (p = 0.004) and lesion intensity [erythema (p = 0.022) and lichenification (p = 0.035)]; and excoriation (p = 0.024) and TEWL (p = 0.009) in the antecubital fossa. The relative risk of isolating moderate-to heavy growth of SA in the most affected area in patients with severe disease (objective SCORAD >40) is 2.73 (1.43-5.21, p = 0.001). Any growth of SA in either swab sites was associated with objective SCORAD and lesion intensity (p = 0.001 0.019). SA had no association with quality of life and other clinical parameters. All specimens of methicillin-sensitive SA were sensitive to cloxacillin. All methicillin-resistant SA (MRSA) (5.7%) was sensitive to co-trimoxazole and fusidic acid. CONCLUSIONS: Clinical features, especially severity and lesion intensity, are useful in "predicting" moderate-to-heavy SA colonization/infection in AD patients. Cloxacillin has a favorable sensitivity profile for MSSA, and co trimoxazole and fusidic acid for MRSA. As colonization and infection are ambiguous and potentially overlapping clinical states, we recommend to abandon these terms and propose to describe quantitatively/semi-quantitatively SA isolation as none, mild, scanty, moderate or heavy growth instead in clinical trials. PMID- 26558413 TI - Face shields for infection control: A review. AB - Face shields are personal protective equipment devices that are used by many workers (e.g., medical, dental, veterinary) for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from splashes, sprays, and spatter of body fluids. Face shields are generally not used alone, but in conjunction with other protective equipment and are therefore classified as adjunctive personal protective equipment. Although there are millions of potential users of face shields, guidelines for their use vary between governmental agencies and professional societies and little research is available regarding their efficacy. PMID- 26558414 TI - A virtual shopping task for the assessment of executive functions: Validity for people with stroke. AB - The importance of assessing executive functions (EF) using ecologically valid assessments has been discussed extensively. Due to the difficulty of carrying out such assessments in real-world settings on a regular basis, virtual reality has been proposed as a technique to provide complex functional tasks under a variety of differing conditions while measuring various aspects of performance and controlling for stimuli. The main goal of this study was to examine the discriminant, construct-convergent and ecological validity of the Adapted Four Item Shopping Task, an assessment of the Instrumental Activity of Daily Living (IADL) of shopping. Nineteen people with stroke, aged 50-85 years, and 20 age- and gender-matched healthy participants performed the shopping task in both the SeeMe Virtual Interactive Shopping environment and a real shopping environment (the hospital cafeteria) in a counterbalanced order. The shopping task outcomes were compared to clinical measures of EF. The findings provided good initial support for the validity of the Adapted Four-Item Shopping Task as an IADL assessment that requires the use of EF for people with stroke. Further studies should examine this task with a larger sample of people with stroke as well as with other populations who have deficits in EF. PMID- 26558417 TI - Risk of elevated transaminases in non-small cell lung cancer (NSCLC) patients treated with erlotinib, gefitinib and afatinib: a meta-analysis. AB - This meta-analysis has been conducted to determine the risk of elevated transaminases associated with the use of erlotinib, gefitinib and afatinib in patients with non-small cell lung cancer (NSCLC). Studies eligible for our analysis included randomized phase II and III trials of patients with NSCLC on the three agents which describe events of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Initial database search revealed 300 relevant citations. After excluding non-eligible studies, 24 trials were considered eligible for the analysis. The relative risk (RR) of all-grade elevated ALT and AST was 1.82 (95% CI: 1.42-2.34; p < 0.00001) and 2.09 (95% CI: 1.54-2.83; p < 0.00001) respectively; while for high-grade elevated ALT and AST, it was 9.23 (95% CI: 5.06-16.85; p < 0.00001) and 1.78 (95% CI: 0.5-6.26; p = 0.37), respectively. Our meta-analysis has shown that there is an overall elevated risk of elevated transaminases with the use of these agents. PMID- 26558416 TI - Cerebrovascular Disease and Chronic Obstructive Pulmonary Disease Increase Risk of Complications with Robotic Partial Nephrectomy. AB - OBJECTIVE: To identify specific comorbidities within the Charlson Comorbidity Index (CCI) that are associated with increased complication rates after robot assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: After institutional review board approval, a consecutive series of 641 patients undergoing RAPN were retrospectively identified. Perioperative complications were defined and classified using the Clavien grading system. Fisher's exact test or chi-square test was performed to evaluate the association of individual comorbidities with perioperative complications. Logistic regression was used for multivariable analysis to adjust for other non-CCI comorbidities and tumor-specific and patient specific characteristics. RESULTS: Of the 641 patients undergoing RAPN, complications occurred in 67 patients (10.5%), including 10 (14.9%), 28 (41.8%), 20 (29.9%), 5 (7.5%), and 4 (6.0%) patients with Clavien grade 1, 2, 3a, 3b, and 4 complications, respectively. Cerebrovascular disease [odds ratio 3.01 (95% confidence interval [CI] 1.10, 8.26) p = 0.03] and chronic obstructive pulmonary disease [COPD; 3.12 (1.24, 7.89) p = 0.02] predicted complications in multivariable analysis of clinicopathologic characteristics, including all CCI and non-CCI comorbidities. In additional modeling with only CCI comorbidities, similar results were observed, with cerebrovascular disease [2.93 (1.04, 7.56) p = 0.04] and COPD [2.69 (1.04, 6.28) p = 0.04] as the only two significant variables. No other variables reached statistical significance in either model, including nephrometry score or estimated blood loss (p > .50 for both). COPD predicted major complications (Clavien grade 3 or 4) in multivariable analysis [3.19 (1.07, 9.48) p = 0.04]. CONCLUSIONS: Cerebrovascular disease and COPD predict perioperative RAPN complications after RAPN. Identification of patients with these comorbidities preoperatively may afford improved counseling and risk stratification. PMID- 26558415 TI - Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology. AB - INTRODUCTION: Dead enzymes are gene products (proteins) that lack key residues required for catalytic activity. In the pre-genome era, dead enzymes were thought to occur only rarely. However, they now have been shown to represent upwards of 10% of the total enzyme population in many families. The aldehyde dehydrogenase (ALDH) gene family encodes proteins that, depending on the isozyme, may be either catalytically-active or -inactive. Importantly, several ALDHs exhibit biological activities independent of their catalytic activity. For many of these, the physiological and pathophysiological functions remain to be established. AREAS COVERED: This article reviews the non-enzymatic functions of the ALDH superfamily. In addition, a search for additional non-catalytic ALDH records is undertaken. Our computational analyses reveal that there are currently 182 protein records (divided into 19 groups) that meet the criteria for dead enzymes. EXPERT OPINION: Dead enzymes have the potential to exert biological actions through protein-protein interaction and allosteric modulation of the activity of an active enzyme. In addition, a dead enzyme may also influence availability of substrate for other active enzymes by sequestering substrate, and/or anchoring the substrate to a particular subcellular space. A large number of putatively non catalytic ALDH proteins exist that warrant further study. PMID- 26558418 TI - Second-generation antidepressants for preventing seasonal affective disorder in adults. AB - BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non randomised studies. Eligible studies compared an SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications and assigned risk of bias ratings based on the Cochrane 'Risk of bias' tool. We resolved disagreements by consensus or by consultation with a third party. Two review authors independently extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi(2) statistic and the Cochran Q. We used the I(2) statistic to estimate the magnitude of heterogeneity and examined potential sources of heterogeneity using sensitivity analysis or analysis of subgroups. We assessed publication bias by using funnel plots. However, given the small number of component studies in our meta-analyses, these tests have low sensitivity to detect publication bias. We rated the strength of the evidence using the system developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. MAIN RESULTS: We identified 2986 citations after de duplication of search results and excluded 2895 records during title and abstract reviews. We assessed 91 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in patients with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; three RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 40% and 50%, NNTBs are 6 (95% CI 5 to 9) and 5 (95% CI 4 to 7), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high risk population, four of five patients will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment and might want to consider offering other potentially efficacious interventions, which might confer lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions. PMID- 26558419 TI - Thrombomodulin as an intravascular safeguard against inflammatory and thrombotic diseases. AB - INTRODUCTION: Thrombomodulin is a transmembrane protein expressed on the surface of endothelial cells. It plays an important role in regulating inflammation as well as coagulation within blood vessels. Recently, a recombinant form of an extracellular fragment of thrombomodulin (rTM) has been developed and is expected to be useful for patients suffering from inflammatory and thrombotic diseases. AREAS COVERED: We initially focus on the physiological and biochemical features of thrombomodulin, including its distribution, structure and function. We then discuss potential therapeutic applications of rTM. EXPERT OPINION: Thrombomodulin exerts anticoagulant and anti-inflammatory effects, in part through activated protein C (APC)-dependent mechanisms. Although recombinant human APC (rhAPC) failed to improve the survival of patients with septic shock and has now been withdrawn from the market, rTM may have some advantages over rhAPC. First, rTM may have less risk of bleeding complications than rhAPC, because rTM needs thrombin to act as an anticoagulant and thus its anticoagulant power can be automatically adjusted by the amount of existing thrombin. Second, the APC independent actions of rTM might confer benefits, including the suppression of complements, endotoxin (representative pathogen-associated molecular pattern) and high-mobility group box 1 protein (prototypical damage-associated molecular pattern) through the lectin-like domain of rTM. PMID- 26558420 TI - Using a blog as an integrated eLearning tool and platform. AB - Technology enhanced learning or eLearning allows educators to expand access to educational content, promotes engagement with students and makes it easier for students to access educational material at a time, place and pace which suits them. The challenge for educators beginning their eLearning journey is to decide where to start, which includes the choice of an eLearning tool and platform. This article will share one educator's decision making process, and experience using blogs as a flexible and versatile integrated eLearning tool and platform. Apart from being a cost effective/free tool and platform, blogs offer the possibility of creating a hyperlinked indexed content repository, for both created and curated educational material; as well as a distribution and engagement tool and platform. Incorporating pedagogically sound activities and educational practices into a blog promote a structured templated teaching process, which can be reproduced. Moving from undergraduate to postgraduate training, educational blogs supported by a comprehensive online case-based repository offer the possibility of training beyond competency towards proficiency and expert level performance through a process of deliberate practice. By documenting educational content and the student engagement and learning process, as well as feedback and personal reflection of educational sessions, blogs can also form the basis for a teaching portfolio, and provide evidence and data of scholarly teaching and educational scholarship. Looking into the future, having a collection of readily accessible indexed hyperlinked teaching material offers the potential to do on the spot teaching with illustrative material called up onto smart surfaces, and displayed on holographic interfaces. PMID- 26558421 TI - Communicating scientific evidence in qualified health claims. AB - Qualified health claims (QHCs) are found on food and dietary supplement labels and aim to communicate the quality and strength of scientific evidence for a diet disease relationship. Since the evidence varies for diet-disease relationships, the language to describe the evidence also varies. However, research indicates that consumers misinterpret QHCs as a whole product evaluation. The FDA is reviewing the evidence ranking system for QHCs and the current study aims to inform future consumer research. A content analysis examined the language used to convey scientific evidence in 53 QHCs and organized them into an intrinsic scale of evidence. Results revealed 36 formats to present the evidence in 53 QHCs. Seventy-seven percent (n = 41) demonstrate a reading level above 9th grade. Most claims describe the quality of evidence (n = 51, 96%) ("very weak") and/or reference its consistency (n = 41, 77%), while a quarter (n = 13) also quantify the evidence ("two studies"). Twenty-five claims (47%) present the evidence before stating the diet-disease relationship. There is an absence of a systematic description of evidence among QHCs that may contribute to the misleading, albeit unintentional, nature of these claims. Policymakers might consider reforming QHC regulations so that a hierarchy of evidence for diet-disease relationships is clearly communicated to consumers. PMID- 26558422 TI - Evaluating the current surgical strategies for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Despite careful surveillance programs and the development of antiviral therapy for hepatitis virus infection, the occurrence rate of HCC remains high. Liver resection and liver transplantation are mainstay curative treatments. Most patients with HCC have impaired liver function, and surgical treatment is always accompanied by the risk of decompensation of the remnant liver, especially when the volume of the remnant liver is too small and the liver function too low to meet metabolic demands. The mortality of liver resection has dramatically decreased over the last three decades from 20% to less than 5% due to the accumulation of knowledge of liver anatomy, perioperative management and preoperative assessment of liver function. Here we provide an overview of the multidisciplinary treatments and current standard treatment strategies for HCC, to explore the possibility of expanding surgical treatments beyond the current standards. PMID- 26558423 TI - De Novo MYC and BCL2 Double-hit B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) in Pediatric and Young Adult Patients Associated With Poor Prognosis. AB - MYC and BCL2 translocations in B-cell lymphomas are defined as "double-hit" associated with poor prognosis in adult patients. Such double-hit events are extremely rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), especially in pediatric patients or young adults. This study is to investigate the clinical manifestation of de novo MYCyBCL2 double-hit BCP-ALL in young patients. Two pediatric and one young adult patients were identified after a retrospective data review and all without previous history of lymphoma. There were two females and one male aged 15, 18, and 24, respectively. All patients had an unremarkable medical history before presenting with extensive bone marrow and central nervous system involvement at diagnosis. Flow cytometry immunophenotypic analysis showed an immature B-cell immunophenotype (CD10+, CD19+, TdT+, surface Ig-) and immunohistochemistry showed high expression of MYC and BCL2 in all cases. All patients showed complex karyotypes associated with 8q24 abnormalities in the form of t(8;9)(q24;p13) or t(8;14)(q24;q32) and t(14;18)(q32;q21) and fluorescence in situ hybridization confirmed MYC and BCL2 rearrangements. Two patients died of refractory disease or disease progression 7 and 13 months after initial diagnosis, respectively, and the third patient was treated with protocol AALL0232 under the Children's Oncology Group study, achieved complete remission and remained in remission for 53 months at last follow-up. Our study showed that De novo MYCyBCL2 double-hit BCP-ALL is a rare disease that also occurs in pediatric and young adult patients and associated with complex karyotypes and poor prognosis. Younger patients may benefit from intensified chemotherapy. PMID- 26558426 TI - Superior catalytic activity derived from a two-dimensional Ti3C2 precursor towards the hydrogen storage reaction of magnesium hydride. AB - The superior catalytic effects derived from a 2D Ti3C2 (MXene), synthesized by the exfoliation of Ti3AlC2 powders, towards the hydrogen storage reaction of MgH2 were demonstrated. The 5 wt% Ti3C2-containing MgH2 releases 6.2 wt% H2 within 1 min at 300 degrees C and absorbs 6.1 wt% H2 within 30 s at 150 degrees C, exhibiting excellent dehydrogenation/hydrogenation kinetics. PMID- 26558427 TI - Progressive Lower Extremity Pain. PMID- 26558424 TI - Immunocapture strategies in translational proteomics. AB - Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field's current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics. PMID- 26558428 TI - High-Flux Hemodialysis Benefits Hemodialysis Patients by Reducing Serum FGF-23 Levels and Reducing Vascular Calcification. AB - BACKGROUND: High- and low-flux hemodialysis (HFHD and LFHD, respectively) are dialysis procedures designed to eliminate blood toxins that accumulate in end stage renal disease. HFHD may reduce vascular calcification by removing serum fibroblast growth factor 23 (FGF-23). However, whether HFHD is better than LFHD is still under debate. We therefore compared the efficacy of HFHD and LFHD in controlling FGF-23 and vascular calcification. MATERIAL AND METHODS: Fifty hemodialysis patients were recruited and randomly treated with either HFHD or LFHD. Fasting venous blood was collected at baseline, six months, and twelve months after the treatment. We then measured levels of FGF-23, calcium, phosphorus, parathyroid hormone, and alkaline phosphatase. Further, abdominal lateral radiographs were taken to calculate aorta abdominalis calcification scores (AACs). RESULTS: Compared to the LFHD group, FGF-23 and AACs in the HFHD group significantly decreased after 12 months treatment (p=0.049 and p=0.002, respectively). AACs were positively correlated with FGF-23 in all patients (p=0.004), the HFHD group alone (p=0.040), and the LFHD group alone (p=0.037). We also found that older patients, patients with higher blood phosphorus levels, and higher FGF-23 levels had an increased risk of aorta abdominalis calcification (p=0.048, p=0.003, p=0.001, respectively). HFHD was more able to reduce the risk of aorta abdominalis calcification than LFHD (p=0.003). CONCLUSIONS: FGF-23 is an independent risk factor for the development of vascular calcification. HFHD may benefit hemodialysis patients by reducing serum FGF-23 levels and controlling vascular calcification. PMID- 26558429 TI - Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain. AB - Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging. PMID- 26558430 TI - Tagaea marina gen. nov., sp. nov., a marine bacterium isolated from shallow coastal water. AB - A Gram-negative, heterotrophic, marine bacterium, designated strain TT1T, was isolated from seawater collected from the shallow coastal region of Anping Harbour, Tainan, Taiwan. Cells grown in broth cultures were straight rods that were motile by means of a single polar flagellum. The isolate required NaCl for growth and exhibited optimal growth at 30-35 degrees C, 2-4 % NaCl and pH 7-8. Strain TT1T grew aerobically and was not capable of anaerobic growth by fermentation of glucose or other carbohydrates. Q-10 was the sole major isoprenoid quinone. Cellular fatty acids were dominated by C18 : 1omega7c (47.5 %), C18 : 1 2-OH (16.3 %) and C19 : 0omega8c cyclo (10.6 %). The DNA G+C content was 56.4 mol%. Phylogeny based on 16S rRNA gene sequences showed that strain TT1T formed a distinct genus-level lineage in the family Rhodospirillaceae of the class Alphaproteobacteria and exhibited the highest sequence similarity with species of the genera Thalassobaculum (89.9-90.0 % 16S rRNA gene sequence similarity), Oceanibaculum (89.4-89.9 %) and Nisaea (89.1-89.7 %). Strain TT1T could be distinguished from species of these phylogenetically closest genera based on differences in DNA G+C contents (56.4 mol% vs 60.0-68.0 mol%), fatty acid profiles and some physiological characteristics. On the basis of the polyphasic taxonomic data from this study, strain TT1T is considered to represent a novel species of a new genus in the family Rhodospirillaceae, for which the name Tagaea marina gen. nov., sp. nov. is proposed. The type strain of the type species is TT1T ( = JCM 18659T = BCRC 80493T). PMID- 26558431 TI - Rebamipide as a novel addition to the antivitiligo ordnance. PMID- 26558432 TI - Elevations of urinary pH may lower vancomycin serum concentration. AB - OBJECTIVE: This study investigated endogenous factors that may increase the elimination of vancomycin (VCM) in adult methicillin-resistant Staphylococcus aureus (MRSA) patients with pneumonia. METHODS: 48 patients (32 men and 16 women) admitted to the National Hospital Organization Kumamoto Medical Center for pneumonia due to MRSA were evaluated. VCM (500 - 2,000 mg/dose) was administered intravenously for 60 - 120 min at 8- - 12-h intervals. The dose of VCM prescribed was determined based on the treatment guidelines of the Infectious Diseases Society of America and was dependent on a patient's creatinine clearance. RESULTS: Univariate analysis identified that potassium value (K) (p = 0.081) and urinary pH (p = 0.026) were possibly associated with decreased VCM concentration. Multivariate analysis confirmed that urinary pH was an independent risk factor for VCM clearance (p = 0.029). VCM clearance in patients with a urine pH of 8 was significantly higher (p = 0.032) than in patients with a urinary pH of 5. As urinary pH increased in alkalinity, a greater decrease in VCM concentrations was observed. CONCLUSIONS: Elevation of urinary pH promotes the urinary excretion of VCM, likely by promoting the dissociation of the carboxyl group of VCM. Thus, in the clinical setting, urinary pH should be measured and considered when determining dosage, as it may affect the VCM blood concentration. PMID- 26558433 TI - Apoptosis-related biomarkers in patients with gastrointestinal cancer. PMID- 26558434 TI - Bioequivalence study of an extemporaneously prepared oral solution of amlodipine suitable for use in pediatric patients compared to commercial tablets. AB - OBJECTIVE: Amlodipine, a long-acting dihydropyridine calcium channel blocker, is frequently prescribed to pediatric patients. To date, no suitable pediatric formulation has been available. In this study, an amlodipine oral solution was developed and tested for bioequivalence to tablets in healthy adult volunteers. METHODS: This study was designed as an open-label, single-dose, twosequence, two period, crossover trial to assess the bioequivalence of a newly developed amlodipine besylate oral solution 0.5 mg/mL compared to Norvasc(r) 5 mg tablets. 13 adult subjects (mean [standard deviation] age of 23.2 [3.6] years, weight 71.5 [7.7] kg) were included and blood samples were collected for 72 hours. Amlodipine plasma levels were determined using a validated UPLC-MS/MS assay. Non compartmental pharmacokinetic parameters were compared between the formulations according to European Medicines Agency (EMA) bioequivalence guidelines. RESULTS: The 90% confidence intervals of the test/reference ratios of the geometric means for the primary pharmacokinetic parameters AUC(0-72) (88.24 - 104.37%) and C(max) (99.00 - 121.40%) were within the acceptance range of 80.00 - 125.00% for bioequivalence. Mean (SD) AUC(0-72) was 102.7 (26.8) (26.8) MUg * h/L for the solution and 108.2 (30.6) MUg * h/L for the tablet. Mean (SD) Cmax of the solution was 3.11(1.06) MUg/L with a median (IQR) t(max) of 4.0 (2.6 - 7.5) hours. Mean (SD) C(max) of the tablet was 2.91 (0.84) MUg/L with a median (IQR) tmax of 6.0 (4.0 - 14.0) hours. Intrasubject coefficients of variation were 10.2% (AUC(0-72)) and 12.4% (C(max)). CONCLUSIONS: The formulations are bioequivalent according to EMA guidelines. This warrants further study of our novel amlodipine oral solution in pediatric patients. PMID- 26558435 TI - The GH5 1,4-beta-mannanase from Bifidobacterium animalis subsp. lactis Bl-04 possesses a low-affinity mannan-binding module and highlights the diversity of mannanolytic enzymes. AB - BACKGROUND: beta-Mannans are abundant and diverse plant structural and storage polysaccharides. Certain human gut microbiota members including health-promoting Bifidobacterium spp. catabolize dietary mannans. Little insight is available on the enzymology of mannan deconstruction in the gut ecological niche. Here, we report the biochemical properties of the first family 5 subfamily 8 glycoside hydrolase (GH5_8) mannanase from the probiotic bacterium Bifidobacterium animalis subsp. lactis Bl-04 (BlMan5_8). RESULTS: BlMan5_8 possesses a novel low affinity carbohydrate binding module (CBM) specific for soluble mannan and displays the highest catalytic efficiency reported to date for a GH5 mannanase owing to a very high k cat (1828 +/- 87 s(-1)) and a low K m (1.58 +/- 0.23 g . L(-1)) using locust bean galactomannan as substrate. The novel CBM of BlMan5_8 mediates increased binding to soluble mannan based on affinity electrophoresis. Surface plasmon resonance analysis confirmed the binding of the CBM10 to manno oligosaccharides, albeit with slightly lower affinity than the catalytic module of the enzyme. This is the first example of a low-affinity mannan-specific CBM, which forms a subfamily of CBM10 together with close homologs present only in mannanases. Members of this new subfamily lack an aromatic residue mediating binding to insoluble cellulose in canonical CBM10 members consistent with the observed low mannan affinity. CONCLUSION: BlMan5_8 is evolved for efficient deconstruction of soluble mannans, which is reflected by an exceptionally low K m and the presence of an atypical low affinity CBM, which increases binding to specifically to soluble mannan while causing minimal decrease in catalytic efficiency as opposed to enzymes with canonical mannan binding modules. These features highlight fine tuning of catalytic and binding properties to support specialization towards a preferred substrate, which is likely to confer an advantage in the adaptation to competitive ecological niches. PMID- 26558436 TI - Global biomass production potentials exceed expected future demand without the need for cropland expansion. AB - Global biomass demand is expected to roughly double between 2005 and 2050. Current studies suggest that agricultural intensification through optimally managed crops on today's cropland alone is insufficient to satisfy future demand. In practice though, improving crop growth management through better technology and knowledge almost inevitably goes along with (1) improving farm management with increased cropping intensity and more annual harvests where feasible and (2) an economically more efficient spatial allocation of crops which maximizes farmers' profit. By explicitly considering these two factors we show that, without expansion of cropland, today's global biomass potentials substantially exceed previous estimates and even 2050s' demands. We attribute 39% increase in estimated global production potentials to increasing cropping intensities and 30% to the spatial reallocation of crops to their profit-maximizing locations. The additional potentials would make cropland expansion redundant. Their geographic distribution points at possible hotspots for future intensification. PMID- 26558437 TI - OASIS modulates hypoxia pathway activity to regulate bone angiogenesis. AB - OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1alpha (HIF-1alpha) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis(-/-)) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1alpha through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis(-/-) osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis(-/-) mice. These results suggest that OASIS affects the expression of HIF-1alpha target genes through the protein interaction with HIF 1alpha, and that OASIS-HIF-1alpha complexes may play essential roles in angiogenesis during bone development. PMID- 26558438 TI - Quercitrin for periodontal regeneration: effects on human gingival fibroblasts and mesenchymal stem cells. AB - Periodontal disease (PD) is the result of an infection and chronic inflammation of the gingiva that may lead to its destruction and, in severe cases, alveolar bone and tooth loss. The ultimate goal of periodontal treatment is to achieve periodontal soft and hard tissues regeneration. We previously selected quercitrin, a catechol-containing flavonoid, as a potential agent for periodontal applications. In this study, we tested the ability of quercitrin to alter biomarker production involved in periodontal regeneration on primary human gingival fibroblasts (hGF) and primary human mesenchymal stem cells (hMSC) cultured under basal and inflammatory conditions. To mimic PD inflammatory status, interleukin-1 beta (IL-1beta) was used. The expression of different genes related to inflammation and extracellular matrix were evaluated and prostaglandin E2 (PGE2) production was quantified in hGFs; alkaline phosphatase (ALP) activity and calcium content were analysed in hMSCs. Quercitrin decreased the release of the inflammatory mediator PGE2 and partially re-established the impaired collagen metabolism induced by IL-1beta treatment in hGFs. Quercitrin also increased ALP activity and mineralization in hMSCs, thus, it increased hMSCs differentiation towards the osteoblastic lineage. These findings suggest quercitrin as a novel bioactive molecule with application to enhance both soft and hard tissue regeneration of the periodontium. PMID- 26558439 TI - From sink to source: Regional variation in U.S. forest carbon futures. AB - The sequestration of atmospheric carbon (C) in forests has partially offset C emissions in the United States (US) and might reduce overall costs of achieving emission targets, especially while transportation and energy sectors are transitioning to lower-carbon technologies. Using detailed forest inventory data for the conterminous US, we estimate forests' current net sequestration of atmospheric C to be 173 Tg yr(-1), offsetting 9.7% of C emissions from transportation and energy sources. Accounting for multiple driving variables, we project a gradual decline in the forest C emission sink over the next 25 years (to 112 Tg yr(-1)) with regional differences. Sequestration in eastern regions declines gradually while sequestration in the Rocky Mountain region declines rapidly and could become a source of atmospheric C due to disturbances such as fire and insect epidemics. C sequestration in the Pacific Coast region stabilizes as forests harvested in previous decades regrow. Scenarios simulating climate induced productivity enhancement and afforestation policies increase sequestration rates, but would not fully offset declines from aging and forest disturbances. Separating C transfers associated with land use changes from sequestration clarifies forests' role in reducing net emissions and demonstrates that retention of forest land is crucial for protecting or enhancing sink strength. PMID- 26558440 TI - Free energies of solvation in the context of protein folding: Implications for implicit and explicit solvent models. AB - Implicit solvent models for biomolecular simulations have been developed to use in place of more expensive explicit models; however, these models make many assumptions and approximations that are likely to affect accuracy. Here, the changes in free energies of solvation upon folding DeltaDeltaGsolv of several fast folding proteins are calculated from previously run MUs-ms simulations with a number of implicit solvent models and compared to the values needed to be consistent with the explicit solvent model used in the simulations. In the majority of cases, there is a significant and substantial difference between the DeltaDeltaGsolv values calculated from the two approaches that is robust to the details of the calculations. These differences could only be remedied by selecting values for the model parameters-the internal dielectric constant for the polar term and the surface tension coefficient for the nonpolar term-that were system-specific or physically unrealistic. We discuss the potential implications of our findings for both implicit and explicit solvent simulations. (c) 2015 Wiley Periodicals, Inc. PMID- 26558441 TI - Evaluation of thyroid isthmusectomy as a potential treatment for papillary thyroid carcinoma limited to the isthmus: A clinical study of 73 patients. AB - BACKGROUND: There are no specific therapeutic guidelines for thyroid cancers confined to the isthmus. To determine whether isthmic papillary thyroid carcinoma (PTC) can be treated with thyroid isthmusectomy and limited neck dissection, we analyzed factors related to central lymph node (CLN) metastasis in patients with clinically node-negative (cN0), solitary, isthmic PTC. METHODS: We retrospectively reviewed 73 consecutive patients who underwent surgery for solitary isthmic, PTC. The frequency, pattern, and risk factors of CLN metastasis were analyzed. RESULTS: Occult CLN metastasis and paratracheal lymph node (PTLN) metastasis were detected in 34 patients (46.6%) and 28 patients (38.4%), respectively. On multivariate logistic regression analysis, male sex and tumor size >0.7 cm were associated with CLN metastasis, and age <=38 years, tumor size >0.6 cm, and pretracheal lymph node positivity were associated with PTLN metastasis. CONCLUSION: Thyroid isthmusectomy for solitary isthmic PTC may be insufficient in patients with tumors >0.6 cm, those aged <=38 years, and male patients. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1510-E1514, 2016. PMID- 26558443 TI - Impact of being overweight on factor VIII dosing in children with haemophilia A. AB - INTRODUCTION: Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) * desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%. AIM: The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA. METHODS: A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery. RESULTS: The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile =P95 (Median FVIII recovery: 2.65). The FVIII recovery was significantly different between these two groups (P < 0.001). CONCLUSION: These results are consistent with previous studies conducted in adults with HA and confirm that the long-held and current practice of applying an arbitrary and universal recovery of two to the calculations of FVIII dosage should be abolished in both children and adults. PMID- 26558442 TI - Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage. AB - Mesenchymal stem cells are known to exert immunomodulatory effects in inflammatory diseases. Immuneregulatory cells lead to progressive joint destruction in rheumatoid arthritis (RA). Proinflammatory cytokines, such as tumour necrosis factor alpha (TNF-alpha) and interleukins (ILs) are the main players. Here, we studied progenitor cells from RA cartilage (RA-CPCs) that are positive for IL-17 receptors to determinate the effects of inflammation on their chondrogenic potenial. IL-17A/F reduced the chondrogenic potential of these cells via the upregulation of RUNX2 protein and enhanced IL-6 protein and MMP3 mRNA levels. Blocking antibodies against IL-17 positively influenced their repair potential. Furthermore, treating the RA-CPCs with the anti-human IL-17 antibody secukinumab or the anti-TNF-alpha antibody adalimumab reduced the proinflammatory IL-6 protein level and positively influenced the secretion of anti-inflammatory IL-10 protein. Additionally, adalimumab and secukinumab in particular reduced RUNX2 protein to promote chondrogenesis. The amelioration of inflammation, particularly via IL-17 antagonism, might be a new therapeutic approach for enhancing intrinsic cartilage repair mechanisms in RA patients. PMID- 26558444 TI - Systematic review to inform prevention and management of chronic disease for Indigenous Australians: overview and priorities. AB - OBJECTIVE: To describe the main characteristics of systematic reviews addressing questions of chronic disease and related risk factors for Indigenous Australians. METHODS: We searched databases for systematic reviews meeting inclusion criteria. Two reviewers assessed quality and extracted characteristics using pre-defined tools. RESULTS: We identified 14 systematic reviews. Seven synthesised evidence about health intervention effectiveness; four addressed chronic disease or risk factor prevalence; and six conducted critical appraisal as per current best practice. Only three reported steps to align the review with standards for ethical research with Indigenous Australians and/or capture Indigenous-specific knowledge. Most called for more high-quality research. CONCLUSION: Systematic review is an under-utilised method for gathering evidence to inform chronic disease prevention and management for Indigenous Australians. Relevance of future systematic reviews could be improved by: 1) aligning questions with community priorities as well as decision maker needs; 2) involvement of, and leadership by, Indigenous researchers with relevant cultural and contextual knowledge; iii) use of critical appraisal tools that include traditional risk of bias assessment criteria and criteria that reflect Indigenous standards of appropriate research. IMPLICATIONS: Systematic review method guidance, tools and reporting standards are required to ensure alignment with ethical obligations and promote rigor and relevance. PMID- 26558445 TI - Synthesis and Characterisation of Fluorescent Carbon Nanodots Produced in Ionic Liquids by Laser Ablation. AB - Carbon nanodots (C-dots) with an average size of 1.5 and 3.0 nm were produced by laser ablation in different imidazolium ionic liquids (ILs), namely, 1-n-butyl-3 methylimidazolium tetrafluoroborate (BMI.BF4 ), 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2 ) and 1-n-octyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (OMI.NTf2 ). The mean size of the nanoparticles is influenced by the imidazolium alkyl side chain but not by the nature of the anion. However, by varying the anion (BF4 vs. NTf2 ) it was possible to detect a significant modification of the fluorescence properties. The C-dots are much probably stabilised by an electrostatic layer of the IL and this interaction has played an important role with regard to the formation, stabilisation and photoluminescence properties of the nanodots. A tuneable broadband fluorescence emission from the colloidal suspension was observed under ultraviolet/visible excitation with fluorescence lifetimes fitted by a multi exponential decay with average values around 7 ns. PMID- 26558447 TI - Applying palliative care principles and practice to emergency medicine. AB - Only recently has the potential (unmet) palliative care (PC) workload in the ED been recognised. While confident in PC symptom management, we underestimate the role of a palliative approach in non-cancer diagnoses and seek education in areas such as individual patient care pathways, ethical and legal issues and difficult conversations at the end of life. PC is best introduced early for a range of life limiting cancer and non-cancer diagnoses. Allowing patients time to tell their story with active listening, acknowledgement of suffering and a compassionate presence leads to treatment 'success' that is not defined by cure. This patient centred, rather than disease-centred approach, is the essence of PC, and one that is easily incorporated into emergency practice. PC and disease-specific treatments can comfortably coexist, and with meticulous symptom management, may actually prolong life. PC is everyone's business, and emergency medicine needs to be part of it. PMID- 26558446 TI - Effectiveness of knee bracing in osteoarthritis: pragmatic trial in a multidisciplinary clinic. AB - AIM: Assessing the effectiveness of bracing treatment for tibiofemoral osteoarthritis (OA) and patellofemoral OA in patients with knee OA. METHOD: This study was conducted within the Osteoarthritis Chronic Care Program (OACCP), a 52 week multidisciplinary non-operative program for OA patients. All participants had symptomatic, radiographic knee OA. Knee bracing with Ossur Unloader One and Tru-pull Lite was offered for participants with medial/lateral tibiofemoral and patellofemoral OA, respectively. Participants were assessed at weeks 0, 12, 26 and 52. The primary outcome was knee pain and function at week 52, as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) pain and activities of daily living (ADL) scores. Linear regression models were used to compare effectiveness for pain and function between three groups (patellofemoral bracing, tibiofemoral bracing and no bracing). RESULT: There were 204 participants; 50 assigned patellofemoral bracing, 86 tibiofemoral bracing and 68 with no bracing. Mean baseline KOOS pain score was 52.9, 41.7 and 43.3 (0-100 scale where 100 represents normal) and mean baseline KOOS ADL score was 55.8, 43.7 and 43.1 for the three groups, respectively. Significant improvements were found in each group at week 52 for KOOS pain score and KOOS ADL. There was no significant difference in KOOS pain (P = 0.12) and ADL score (P = 0.13) at week 52 between the three brace types after adjusting for baseline variables. CONCLUSION: A multidisciplinary non-operative program improved pain and function in persons with patellofemoral and tibiofemoral OA. However, wearing a patellofemoral or a tibiofemoral brace did not appear to provide additional benefits. PMID- 26558448 TI - Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration. AB - Guinea pigs are the most frequently used animals in phototoxicity studies. However, general toxicity studies most often use Sprague-Dawley (SD) rats. To reduce the number of animals needed for drug development, we examined whether skin phototoxicity studies could be performed using SD rats. A total of 19 drugs that had previously been shown to have phototoxic potential and 3 known phototoxic compounds were administered transdermally to guinea pigs and SD rats. Eleven of the potentially phototoxic drugs and 2 of the known phototoxic compounds were also administered orally to guinea pigs and SD rats. After administration, the animals were irradiated with UV-A (10 J/cm(2)) and UV-B (0.25 J/cm(2) in guinea pigs and 0.031 J/cm(2) in SD rats) with doses based on standard phototoxicity study guidelines and the results of a minimum erythema dose test, respectively. In the transdermal administration study, all of the known phototoxic compounds and 7 of the drugs induced phototoxic reactions. In the oral administration study, both known phototoxic compounds and 5 drugs induced phototoxic reactions in both species; one compound each was found to be toxic only in SD rats or guinea pigs. The concordance rate of guinea pigs and SD rats was 100% in the transdermal administration study and 85% in the oral administration study. This study demonstrated that phototoxicity studies using SD rats have the same potential to detect phototoxic compounds as studies using guinea pigs. PMID- 26558449 TI - Gene expression analysis in the lung of the rasH2 transgenic mouse at week 4 prior to induction of malignant tumor formation by urethane and N methylolacrylamide. AB - The rasH2 transgenic (Tg) mice are susceptible to genotoxic and some non genotoxic carcinogens. In carcinogenicity studies carried out using rasH2 Tg mice, the carcinogenic potential of chemicals are evaluated over a 26-week experimental period. In the present study, we examined the comprehensive gene expressions in the lungs of Tg and non-Tg mice prior to the induction of malignant tumors. Urethane (UR), a mutagenic carcinogen, was administered for 4 weeks, and thereafter withdrawn for 22 weeks. N-methylolacrylamide (NMA), a non mutagenic carcinogen, was administered for 26 weeks. At week 4, gene expression analysis of non-neoplastic part of the lungs demonstrated changes in the expressions of the cell-cycle and inflammation related genes following UR and NMA treatment, respectively, in both the Tg and non-Tg mice. The gene expressions of epireguline, aurora kinase B, and cyclin B1 increased in the UR-treated Tg mice. We also found an increase in the plasma carcinoembryonic antigen level in the UR treated Tg mice. Although UR treatment induced the formation of adenomas or adenocarcinomas in the lungs in all mice, earlier induction was apparent in the Tg mice. NMA treatment was found to induce the formation of adenomas and adenocarcinomas at week 26 in the Tg mice, but not in the non-Tg mice, and no expressions of specific genes were apparent in either genotype of mice. Our results indicate that analysis of cancer-related gene expressions in the lungs and plasma biomarkers at week 4 in rasH2 Tg mice could be a screening tool for carcinogenicity, especially of mutagenic carcinogens. PMID- 26558450 TI - Tris-(2,3-dibromopropyl) isocyanurate induces depression-like behaviors and neurotoxicity by oxidative damage and cell apoptosis in vitro and in vivo. AB - Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood-brain barrier and accumulate in the brain. TDBP-TAZTO might also induce neuronal cell toxicity. However, the neurotoxicity and mechanisms of TDBP-TAZTO have not yet been studied. We hypothesize that TDBP-TAZTO could induce neurotoxicity in mouse hippocampal neurons and SH-SY5Y cells. The mice were exposed to TDBP-TAZTO of 5 and 50 mg/kg by gavage, daily for 30 days. TDBP-TAZTO resulted in depression-like behaviors, which may be related with TDBP-TAZTO induced upregulation of oxidative stress markers and overexpression of pro apoptotic proteins in hippocampus. Furthermore, TDBP-TAZTO treatment for 48 hr (12.5, 25 and 50 uM) damaged SH-SY5Y cells, and led to cell apoptosis and oxidative stress in concentration-dependent manner. Our findings suggested that cell apoptosis and oxidative stress are important mechanisms in neurotoxicity induced by TDBP-TAZTO. PMID- 26558451 TI - Association of A118G polymorphism in the MU-opioid receptor gene with smoking behaviors: a meta-analysis. AB - Many studies have investigated the association between the A118G polymorphism in the MU-opioid receptor gene and smoking behaviors, but the results remain controversial. This meta-analysis aimed to derive a more reliable estimate of the effect of the A118G polymorphism on smoking behaviors. We systematically searched the PubMed/Medline, Embase and Web of Science databases for eligible articles published up to October 23, 2014. A total of six studies were selected. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between A118G polymorphism and smoking behaviors in four genetic models. Heterogeneity analysis and publication bias were also performed. Subgroup analysis was conducted according to different ethnicities. The meta-analysis was performed using either a fixed- or random-effects model as deemed appropriate. In the result of the meta-analysis, a significant association was detected in the dominant model in the Caucasian subgroup (OR = 3.26, 95% CI = 2.65-4.05). This result indicated that Caucasians carrying the G allele (AG + GG) of the A118G polymorphism in the MU-opioid receptor gene were more likely to be addicted to smoking compared with those with the AA homozygote. However, no significant association was found in other genetic models. PMID- 26558452 TI - The effects of long-lasting hypoglycemia on male reproductive organs in rats. AB - Glucose has an important role in spermatogenesis. Nevertheless there are few reports in which the effects of long-lasting hypoglycemia on male reproductive organs have been evaluated. Therefore, insulin was administered subcutaneously at 100, 200, and 400 IU/kg to male rats twice a day for one month. This treatment regimen produced plasma glucose levels that rapidly decreased after treatment, with decreased glucose levels lasting for several hours after each administration on the first and final treatment days. During the treatment period, no abnormalities in clinical signs or body weight were observed. No statistically significant differences were noted in the weights of testes, epididymides, prostates and seminal vesicles, or pituitary glands. Histopathological examination revealed that the insulin-treated animals exhibited degeneration of seminiferous tubules in the testes and exfoliation of germ cells in the lumens of epididymides as a secondary change related to the testicular lesions. The incidences of the histopathological findings were found to be proportional to insulin dose. Sperm analysis of the group receiving the highest dosage indicated that the sperm concentration tended to decrease and the incidences of sperm malformations tended to increase. Our results suggest that long-lasting hypoglycemia affects male reproductive organs in rats. PMID- 26558453 TI - Dose-dependent acceleration in the delayed effects of neonatal oral exposure to low-dose 17alpha-ethynylestradiol on reproductive functions in female Sprague Dawley rats. AB - Xenoestrogen exposure during the critical period of sexual differentiation of the brain causes delayed effects on female reproduction. We investigated the internal dose of orally administered ethynylestradiol (EE) during the critical period and its delayed effects by administering 0 (vehicle control), 0.4, or 2 MUg/kg EE to female Sprague-Dawley rats for 5 days from postnatal day (PND) 1. Determination of serum EE level 24 hr after the initial dosing and 6 and 24 hr after the final dosing of 2 MUg/kg indicated that the administered EE entered the circulation and cleared after every administration. Although the treatment did not affect physical development, including growth, eyelid opening, and vaginal opening, the estrous cycle was arrested from postnatal week (PNW) 12 even with 0.4 MUg/kg EE, with an inverse correlation between doses and arresting ages. Although ovarian morphology at PNW 22-23 indicated that the treatment caused long-term anovulation and cystic follicle formation, the number of primordial follicles at PNW 22-23 was similar among the groups. Because this number was lower than that at PND 10 in all groups, primordial follicles may have been consumed under long-term anovulation. The treatment also caused other abnormalities, including mammary gland hyperplasia, increase in pituitary and liver weights, and decrease in the uterine weight. Because the highest circulating EE level in the 2 MUg/kg-treated neonates is considered to be comparable to the physiological range of estradiol 17beta, we concluded that a slight increase in the circulating estrogens during the neonatal period exerts irreversible delayed effects. PMID- 26558454 TI - Cannabidiol-2',6'-dimethyl ether stimulates body weight gain in apolipoprotein E deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice. AB - The biological activities of cannabidiol (CBD), a major non-psychotropic constituent of the fiber-type cannabis plant, have been examined in detail (e.g., CBD modulation of body weight in mice and rats). However, few studies have investigated the biological activities of cannabidiol-2',6'-dimethyl ether (CBDD), a dimethyl ether derivative of the parent CBD. We herein focused on the effects of CBDD on body weight changes in mice, and demonstrated that it stimulated body weight gain in apolipoprotein E (ApoE)-deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice, especially between 10 and 20 weeks of age. PMID- 26558455 TI - Anaphylactic augmentation by epicutaneous sensitization to acid-hydrolyzed wheat protein in a guinea pig model. AB - Recent reports suggest that hydrolyzed wheat protein (HWP) variants such as Glupearl(r) 19S (GP19S) induce immediate-type hypersensitivity via epicutaneous (EC) sensitization. The identification of strong allergens is a key step in product assessment before commercial launch. However, few reports have described the estimation of actual and potential anaphylactic sensitizing capacity. In this study we assessed the strength of both the actual and potential anaphylactic sensitizing capacity by investigating the immediate-type hypersensitivity inducing potential of HWP compared with gluten. We assessed these strengths via the EC route using an EC or intradermal (ID) sensitization method. We quantified the strength of immediate-type hypersensitivity by evaluating the titer of serum antibodies isolated from sensitized subjects using passive cutaneous anaphylaxis (PCA) reactions. We also evaluated the cross-reactivity between GP19S and gluten. GP19S and gluten applied by both the sensitization methods induced obvious IgG1 mediated PCA reactions. GP19S had stronger sensitizing potential than gluten, according to the serum titers and dye spot diameters. The difference in antibody titers between GP19S and gluten was 16-fold for the EC method versus 2-fold for the ID method. GP19S cross-reacted with gluten. Acid hydrolysis of gluten increased anaphylactic sensitizing capacity in the EC method. To our knowledge, our study is the first to quantitatively confirm that HWP and gluten can induce immediate-type hypersensitivity through an intact skin. These findings suggest that acid-HWP imposes a higher risk of EC sensitization than gluten because of the ease with which the former confers a sensitizing effect through the intact skin. PMID- 26558456 TI - Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor. AB - It has been noticed that crosstalk between androgen receptor (AR) and mammalian target of rapamycin (mTOR) signaling pathways plays a crucial role in the proliferation of prostate cancer cells. To clarify this mechanism, we focused on DEPTOR, a naturally occurring inhibitor of mTOR. The treatment of a human AR positive prostate cancer cell line, LNCaP, with the AR-agonist dihydrotestosterone (DHT) repressed DEPTOR mRNA expression in a time-dependent manner. This repression was abrogated by treatment with the AR-antagonist bicalutamide. Knockdown of DEPTOR mRNA by siRNA resulted in the increased phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (S6K), a substrate of mTORC1, accompanied by the elevated expression of cyclin D1, a positive regulator of cell proliferation. Furthermore, the ChIP assay demonstrated that AR could bind to AR-responsible element-like region within the 4th intron of the DEPTOR gene. The amount of acetylated histone H3 (Lys9, Lys14) was reduced by the DHT treatment in this region. Taken together, these results propose that AR-dependent prostate cancer cell proliferation requires decreased DEPTOR transcription directly controlled by AR. PMID- 26558457 TI - Assessing the therapeutic efficacy of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig. AB - Given the rapid onset of symptoms from intoxication by organophosphate (OP) compounds, a quick-acting, efficacious therapeutic regimen is needed. A primary component of anti-OP therapy is an oxime reactivator to rescue OP-inhibited acetylcholinesterases. Male guinea pigs, clipped of hair, received neat applications of either VR, VX, parathion, or phorate oxon (PHO) at the 85(th) percentile lethal dose, and, beginning with presentation of toxicosis, received the human equivalent dose therapy by intramuscular injection with two additional follow-on treatments at 3-hr intervals. Each therapy consisted of atropine free base at 0.4 mg/kg followed by one of eight candidate oximes. Lethality rates were obtained at 24 hr after VR, VX and PHO challenges, and at 48 hr after challenge with parathion. Lethality rates among symptomatic, oxime-treated groups were compared with that of positive control (OP-challenged and atropine-only treated) guinea pigs composited across the test days. Significant (p <= 0.05) protective therapy was afforded by 1,1-methylene bis(4(hydroxyimino- methyl)pyridinium) dimethanesulfonate (MMB4 DMS) against challenges of VR (p <= 0.001) and VX (p <= 0.05). Lethal effects of VX were also significantly (p <= 0.05) mitigated by treatments with oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1 yl]methoxymethyl]pyridin-4-ylidene]methyl]azanium dichloride (obidoxime Cl2) and 1-(((4-(aminocarbonyl) pyridinio)methoxy)methyl)-2,4 bis((hydroxyimino)methyl)pyridinium dimethanesulfonate (HLo-7 DMS). Against parathion, significant protective therapy was afforded by obidoxime dichloride (p <= 0.001) and 1,1'-propane-1,3-diylbis{4-[(E)-(hydroxyimino)methyl]pyridinium} dibromide (TMB-4, p <= 0.01). None of the oximes evaluated was therapeutically effective against PHO. Across the spectrum of OP chemicals tested, the oximes that offered the highest level of therapy were MMB4 DMS and obidoxime dichloride. PMID- 26558458 TI - Effects of scorched food leachates with or without activated charcoal pretreatment on AhR activation in cultured cells. AB - Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health. PMID- 26558459 TI - Dose-dependent difference of nuclear receptors involved in murine liver hypertrophy by piperonyl butoxide. AB - Nuclear receptors play important roles in chemically induced liver hypertrophy in rodents. To clarify the involvement of constitutive androstane receptor (CAR) and other nuclear receptors in mouse liver hypertrophy induced by different doses of piperonyl butoxide (PBO), wild-type and CAR-knockout mice were administered PBO (200, 1,000, or 5,000 ppm) in the basal diet for 1 week. Increased liver weight and diffuse hepatocellular hypertrophy were observed at 5,000 ppm for both genotypes, accompanied by increased Cyp3a11 mRNA and CYP3A protein expression, suggesting that CAR-independent pathway, possibly pregnane X receptor (PXR), plays a major role in the induction of hypertrophy. Moreover, wild-type mice at 5,000 ppm showed enhanced hepatocellular hypertrophy and strong positive staining for CYP2B in the centrilobular area, suggesting the localized contribution of CAR. At 1,000 ppm, only wild-type mice showed liver weight increase and centrilobular hepatocellular hypertrophy concurrent with elevated Cyp2b10 mRNA expression and strong CYP2B staining, indicating that CAR was essential at 1,000 ppm. We concluded that high-dose PBO induced hypertrophy via CAR and another pathway, while lower dose of PBO induced a pathway mediated predominantly by CAR. The dose-responsiveness on liver hypertrophy is important for understanding the involvement of nuclear receptors. PMID- 26558460 TI - Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing. AB - Cannabis concentrates are gaining rapid popularity in the California medical cannabis market. These extracts are increasingly being consumed via a new inhalation method called 'dabbing'. The act of consuming one dose is colloquially referred to as "doing a dab". This paper investigates cannabinoid transfer efficiency, chemical composition and contamination of concentrated cannabis extracts used for dabbing. The studied concentrates represent material available in the California medical cannabis market. Fifty seven (57) concentrate samples were screened for cannabinoid content and the presence of residual solvents or pesticides. Considerable residual solvent and pesticide contamination were found in these concentrates. Over 80% of the concentrate samples were contaminated in some form. THC max concentrations ranged from 23.7% to 75.9% with the exception of one outlier containing 2.7% THC and 47.7% CBD. Up to 40% of the theoretically available THC could be captured in the vapor stream of a dab during inhalation experiments. Dabbing offers immediate physiological relief to patients in need but may also be more prone to abuse by recreational users seeking a more rapid and intense physiological effect. PMID- 26558461 TI - Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen(r). AB - Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen(r) is a gene expression based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen(r), originally developed with F344 rats, with two carcinogens, 2,4 diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen(r). Predictive scores obtained by the CARCINOscreen(r) for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen(r), can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens. PMID- 26558462 TI - Classification of reproductive toxicants with diverse mechanisms in the embryonic stem cell test. AB - The embryonic stem cell test (EST) is a promising system to detect embryotoxicity in vitro. Recent studies have pointed out some limitations of the EST and suggest that the applicability domain of the EST and its prediction model have to be better defined. Here, eight substances of known reproductive toxicity were tested in the EST under blind conditions. We applied the prediction model to the data of the EST after classifying the substances according to the published criteria. In addition, a simplified classification of the EST results into two classes as an approach to hazard assessment was compared to the European Union Classification, Labelling and Packaging (CLP) Regulation labels of the substances. With one exception, substances that are labeled as reproductive toxicants according to the CLP Regulation were detected as embryotoxic in the EST while substances without label were found to be non-embryotoxic according to the EST. PMID- 26558463 TI - Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells. AB - Exposure to environmental chemicals has been implicated as a possible risk factor for the development of neurodegenerative diseases. Our previous study showed that methylmercury (MeHg) exposure can disrupt synthesis, uptake and metabolism of dopamine similar to 1-methyl-4-phenylpyridinium (MPP(+)). The objective of this study was to investigate the effects of MeHg exposure on gene and protein profiles in a dopaminergic MN9D cell line. MN9D cells were treated with MeHg (1-5 MUM) and MPP(+) (10-40 MUM) for 48 hr. Real-time PCR Parkinson's disease (PD) arrays and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) were performed for the analysis. PD PCR array results showed that 19% genes were significantly changed in the 2.5 MUM MeHg treated cells, and 39% genes were changed in the 5 MUM MeHg treated cells. In comparison, MPP(+) treatment (40 uM) resulted in significant changes in 25% genes. A total of 15 common genes were altered by both MeHg and MPP(+), and dopaminergic signaling transduction was the most affected pathway. Proteomic analysis identified a total of 2496 proteins, of which 188, 233 and 395 proteins were differentially changed by 1 MUM and 2.5 MUM MeHg, and MPP(+) respectively. A total of 61 common proteins were changed by both MeHg and MPP(+) treatment. The changed proteins were mainly involved in energetic generation-related metabolism pathway (propanoate metabolism, pyruvate metabolism and fatty acid metabolism), oxidative phosphorylation, proteasome, PD and other neurodegenerative disorders. A total of 7 genes/proteins including Ube2l3 (Ubiquitin-conjugating enzyme E2 L3) and Th (Tyrosine 3-monooxygenase) were changed in both genomic and proteomic analysis. These results suggest that MeHg and MPP(+) share many similar signaling pathways leading to the pathogenesis of PD and other neurodegenerative diseases. PMID- 26558464 TI - Differences in gene expression profiles in liver caused by different types of anesthesia: cases of CO2-O2 and isoflurane. AB - Anesthesia is used for pain control and is necessary in toxicological studies. In this study, we examined the effects of anesthesia on gene expression profiles caused by different types of anesthesia. To elucidate the effects of anesthesia on gene expression profiles, DNA microarray analysis was performed with CO2-O2 anesthesia and isoflurane anesthesia, and gene expression profiles in the liver were analyzed. Consequently, a total of 209 probes out of 61,573 showed higher or lower expression levels in the isoflurane anesthesia group compared with CO2-O2 anesthesia. This is less than 0.34% of all probes, indicating that the effects of different types of anesthesia on gene expression profiles are limited. However, careful consideration should be taken in the cases of handling the disturbed genes using DNA microarray, especially in case of research on glutathione-related pathway under isoflurane anesthesia. PMID- 26558465 TI - Protective effects of hydrogen sulfide anions against acetaminophen-induced hepatotoxicity in mice. AB - The key mechanism for hepatotoxicity resulting from acetaminophen (APAP) overdose is cytochrome P450-dependent formation of N-acetyl-p-benzoquinone imine (NAPQI), a potent electrophilic metabolite that forms protein adducts. The fundamental roles of glutathione in the effective conjugation/clearance of NAPQI have been established, giving a molecular basis for the clinical use of N-acetylcysteine as a sole antidote. Recent evidence from in vitro experiments suggested that sulfide anions (S(2-)) to yield hydrogen sulfide anions (HS(-)) under physiological pH could effectively react with NAPQI. This study evaluated the protective roles of HS(-) against APAP-induced hepatotoxicity in mice. We utilized cystathionine gamma-lyase-deficient (Cth(-/-)) mice that are highly sensitive to acetaminophen toxicity. Intraperitoneal injection of acetaminophen (150 mg/kg) into Cth(-/-) mice resulted in highly elevated levels of serum alanine/aspartate aminotransferases and lactate dehydrogenase associated with marked increases in oncotic hepatocytes; all of which were significantly inhibited by intraperitoneal preadministration of sodium hydrosulfide (NaHS). NaHS preadministration significantly suppressed APAP-induced serum malondialdehyde level increases without abrogating APAP-induced rapid depletion of hepatic glutathione. These results suggest that exogenous HS(-) protects hepatocytes by directly scavenging reactive NAPQI rather than by increasing cystine uptake and thereby elevating intracellular glutathione levels, which provides a novel therapeutic approach against acute APAP poisoning. PMID- 26558466 TI - Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay. AB - The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE. PMID- 26558467 TI - Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats. AB - We aimed to clarify the hepatocarcinogen-specific disruption of cell cycle checkpoint functions and its time course after repeated administration of hepatocarcinogens. Thus, rats were repeatedly administered with hepatocarcinogens (methapyrilene, carbadox and thioacetamide), a marginal hepatocarcinogen (leucomalachite green), hepatocarcinogenic promoters (oxfendazole and beta naphthoflavone) or non-carcinogenic hepatotoxicants (promethazine and acetaminophen) for 7, 28 or 90 days, and the temporal changes in cell proliferation, expression of G1/S and spindle checkpoint-related molecules, and apoptosis were examined using immunohistochemistry and/or real-time RT-PCR analysis. Hepatocarcinogens facilitating cell proliferation at day 28 of administration also facilitated cell proliferation and apoptosis at day 90. Hepatocarcinogen- or hepatocarcinogenic promoter-specific cellular responses were not detected by immunohistochemical single molecule analysis even after 90 days. Expression of Cdkn1a, Mad2l1, Chek1 and Rbl2 mRNA also lacked specificity to hepatocarcinogens or hepatocarcinogenic promoters. In contrast, all hepatocarcinogens and the marginally hepatocarcinogenic leucomalachite green induced Mdm2 upregulation or increase in the number of phosphorylated MDM2(+) cells from day 28, irrespective of the lack of cell proliferation facilitation by some compounds. However, different Tp53 expression levels suggest different mechanisms of induction or activation of MDM2 among hepatocarcinogens. On the other hand, hepatocarcinogenic methapyrilene and carbadox downregulated the number of both ubiquitin D(+) cells and proliferating cells remaining in M phase at day 28 and/or day 90, irrespective of the lack of cell proliferation facilitation in the latter. These results suggest that hepatocarcinogens disrupt spindle checkpoint function after 28 or 90 days of administration, which may be induced ahead of cell proliferation facilitation. PMID- 26558468 TI - Covalent binding of quinones activates the Ah receptor in Hepa1c1c7 cells. AB - Highly reactive quinone species produced by photooxidation and/or metabolic activation of mono- or bi-aromatic hydrocarbons modulate cellular homeostasis and electrophilic signal transduction pathways through the covalent modification of proteins. Polycyclic aromatic hydrocarbons, but not mono- or bi-aromatic hydrocarbons, are well recognized as ligands for the aryl hydrocarbon receptor (AhR). However, quinone species produced from mono- and bi-aromatic hydrocarbons could potentially cause AhR activation. To clarify the AhR response to mono- and bi-aromatic hydrocarbon quinones, we studied Cyp1a1 (cytochrome P450 1A1) induction and AhR activation by these quinones. We detected Cyp1a1 induction during treatment with quinones in Hepa1c1c7 cells, but not their parent compounds. Nine of the twelve quinones with covalent binding capability for proteins induced Cyp1a1. Cyp1a1 induction mediated by 1,2-naphthoquinone (1,2 NQ), 1,4-NQ, 1,4-benzoquinone (1,4-BQ) and tert-butyl-1,4-BQ was suppressed by a specific AhR inhibitor and was not observed in c35 cells, which do not have a functional AhR. These quinones stimulated AhR nuclear translocation and interaction with the AhR nuclear translocator. Interestingly, 1,2-NQ covalently modified AhR, which was detected by an immunoprecipitation assay using a specific antibody against 1,2-NQ, resulting in enhancement of xenobiotic responsive element (XRE)-derived luciferase activity and binding of AhR to the Cyp1a1 promoter region. While mono- and bi-aromatic hydrocarbons are generally believed to be poor ligands for AhR and hence unable to induce Cyp1a1, our study suggests that the quinones of these molecules are able to modify AhR and activate the AhR/XRE pathway, thereby inducing Cyp1a1. Since we previously reported that 1,2 NQ and tert-butyl-1,4-BQ also activate NF-E2-related factor 2, it seems likely that some of quinones are bi-functional inducers for phase-I and phase-II reaction of xenobiotics. PMID- 26558469 TI - S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells. AB - Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins. In this study, we identified proteins that undergo S mercuration by MeHg. By combining two-dimensional SDS-PAGE, atomic absorption spectrometry and ultra performance liquid chromatography mass spectrometry (UPLC/MS/MS), we revealed that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a target for S-mercuration in human neuroblastoma SH-SY5Y cells exposed to MeHg (1 uM, 9 hr). The modification site of UCH-L1 by MeHg was Cys152, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. MeHg was shown to inhibit the catalytic activity of recombinant human UCH-L1 in a concentration-dependent manner. Knockdown of UCH-L1 indicated that this enzyme plays a critical role in regulating mono-ubiquitin (monoUb) levels in SH-SY5Y cells and exposure of SH-SY5Y cells to MeHg caused a reduction in the level of monoUb in these cells. These observations suggest that UCH-L1 readily undergoes S-mercuration by MeHg through Cys152 and this covalent modification inhibits UCH-L1, leading to the potential disruption of the maintenance of cellular monoUb levels. PMID- 26558470 TI - Cisplatin-mediated cytotoxicity through inducing CYP4A 11 expression in human renal tubular epithelial cells. AB - Cisplatin (CP) is a major antineoplastic drug for the treatment of solid tumors, but it has dose-dependent renal tubular toxicity. Previous studies have shown that induction of cytochrome P450 (CYP) by CP may play a role in the renal injury of CP. The aim of this study was to investigate the relationship between CP induced toxicity and CYP4A11 expression in human renal tubular epithelial cells (HK-2). 20-Hydroxyeicosatetraenoic acid (20-HETE) is a CYP4A11 metabolite of arachidonic acid that plays an important role in renal injury. The activity of lactate dehydrogenase (LDH) was determined by spectrophotometer. CYP4A11 expression was analyzed by immunocytochemistry. CYP4A11 mRNA and protein expression were evaluated by RT-PCR and Western blot analyses. Results showed that 20-HETE (1, 10, 50 MUM), a CYP4A11 metabolite of arachidonic acid, significantly increased lactate dehydrogenase (LDH) release in these cells. When CP (10(-4) M) and 20-HETE (1, 10, 50 MUM) were co-applied to these cells, CP induced LDH release was significantly exaggerated by 20-HETE. Furthermore, clofibrate, a CYP4A inducer, also increased LDH release in CP-treated cells. In contrast, the CYP4A inhibitor N-Hydrocy-N'-(-4-butyl-2-methylphenyl) formamidine (HET-0016) decreased LDH release in CP-treated cells. Immunocytochemical analysis showed that CYP4A11expression was much stronger in CP-(10(-4) M) treated cells than that in clofibrate-treated cells. Further RT-PCR and Western blot analyses demonstrated that CYP4A11 mRNA and protein expression were significantly up regulated in CP- (10(-4) M) treated cells compared to the clofibrate group. The findings of this study indicate that CP is a potent inducer of CYP4A11, and it exerts its toxic functions via the induction of CYP4A11 and 20-HETE generation. PMID- 26558471 TI - Involvement of ubiquitin-coding genes in cadmium-induced protein ubiquitination in human proximal tubular cells. AB - Cadmium (Cd) is a toxic heavy metal with a long half-life in humans. It causes disorders of various tissue systems, including the kidney, and is associated with protein aggregation. Our previous study demonstrated Cd-induced suppression of the UBE2D gene family, one of the ubiquitin-conjugating enzyme families. However, the precise role of ubiquitin-coding genes in Cd toxicity remains to be understood. In this study, we investigated the effect of Cd on expression of the ubiquitin-coding genes UBB, UBC, UBA80, and UBA52 in HK-2 human proximal tubular cells. Prior to the appearance of Cd toxicity, the UBB, UBC, and UBA80 expression levels increased following Cd treatment. Knockdown of UBB by siRNA transfection significantly decreased Cd cytotoxicity. Notably, Cd induces ubiquitinated protein levels in HK-2 cells, and knockdown of UBB blocked this process. These results suggest that UBB is involved in Cd-induced increase of protein ubiquitination, and that accumulation of ubiquitinated proteins through increased UBB expression may contribute to Cd toxicity in HK-2 cells. PMID- 26558472 TI - Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration. AB - The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a beta-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2 ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2',4,4' tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHbeta mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHbeta. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis. PMID- 26558473 TI - Development of antimicrobial active packaging materials based on gluten proteins. AB - BACKGROUND: The incorporation of natural biocide agents into protein-based bioplastics, a source of biodegradable polymeric materials, manufactured by a thermo-mechanical method is a way to contribute to a sustainable food packaging industry. This study assesses the antimicrobial activity of 10 different biocides incorporated into wheat gluten-based bioplastics. The effect that formulation, processing, and further thermal treatments exert on the thermo-mechanical properties, water absorption characteristics and rheological behaviour of these materials is also studied. RESULTS: Bioplastics containing six of the 10 examined bioactive agents have demonstrated suitable antimicrobial activity at 37 degrees C after their incorporation into the bioplastic. Moreover, the essential oils are able to create an antimicrobial atmosphere within a Petri dish. CONCLUSION: Depending on the selected biocide, its addition may alter the bioplastics protein network in a different extent, which leads to materials exhibiting less water uptake and different rheological and thermo-mechanical behaviours. (c) 2015 Society of Chemical Industry. PMID- 26558474 TI - Effects of TNF-alpha antagonism in patients with metabolic syndrome and psoriasis. PMID- 26558476 TI - New types of fraud in the academic world by cyber criminals. PMID- 26558475 TI - Blood Pressure Measurement Modalities: A Primer for Busy Practitioners. PMID- 26558477 TI - Incidence of prolonged postoperative ileus after colorectal surgery: a systematic review and meta-analysis. AB - AIM: Prolonged postoperative ileus (PPOI) after colorectal surgery remains a leading cause of delayed postoperative recovery and prolonged hospital stay. Its exact incidence is unknown. The aim of this systematic review is to investigate the definitions and incidence of PPOI previously described. METHOD: MEDLINE, Embase and the Cochrane Database of Systematic Reviews (up to July 2014) were searched. Two authors independently reviewed citations using predefined inclusion and exclusion criteria. RESULTS: The search strategy yielded 3233 citations; 54 were eligible, comprising 18 983 patients. Twenty-six studies were prospective [17 of these being randomized controlled trials (RCTs)] and 28 were retrospective. Meta-analysis revealed an incidence of PPOI of 10.3% (95% CI 8.4 12.5) and 10.2% (95% CI 5.6-17.8) for non-RCTs and RCTs, respectively. Significant heterogeneity was observed for both non-RCTs and for RCTs. The used definition of PPOI, the type of surgery and access (laparoscopic, open) and the duration of surgery lead to significant variability of reported PPOI incidence between studies. The incidence of PPOI is lower after laparoscopic colonic resection. CONCLUSION: There is a large variation in the reported incidence of PPOI. A uniform definition of PPOI is needed to allow meaningful inter-study comparisons and to evaluate strategies to prevent PPOI. PMID- 26558478 TI - Hydrogen retention in beryllium: concentration effect and nanocrystalline growth. AB - We herein report on the formation of BeD2 nanocrystalline domes on the surface of a beryllium sample exposed to energetic deuterium ions. A polycrystalline beryllium sample was exposed to D ions at 2 keV/atom leading to laterally averaged deuterium areal densities up to 3.5 10(17) D cm(-2), and studied using nuclear reaction analysis, Raman microscopy, atomic force microscopy, optical microscopy and quantum calculations. Incorporating D in beryllium generates a tensile stress that reaches a plateau at ~1.5 10(17) D cm(-2). For values higher than 2.0 10(17) cm(-2), we observed the growth of ~90 nm high dendrites, covering up to 10% of the surface in some zones of the sample when the deuterium concentration was 3 * 10(17) D cm(-2). These dendrites are composed of crystalline BeD2, as evidenced by Raman microscopy and quantum calculations. They are candidates to explain low temperature thermal desorption spectroscopy peaks observed when bombarding Be samples with D ions with fluencies higher than 1.2 10(17) D cm(-2). PMID- 26558479 TI - Population genetic evidence for cold adaptation in European Drosophila melanogaster populations. AB - We studied Drosophila melanogaster populations from Europe (the Netherlands and France) and Africa (Rwanda and Zambia) to uncover genetic evidence of adaptation to cold. We present here four lines of evidence for genes involved in cold adaptation from four perspectives: (i) the frequency of SNPs at genes previously known to be associated with chill-coma recovery time (CCRT), startle reflex (SR) and resistance to starvation stress (RSS) vary along environmental gradients and therefore among populations; (ii) SNPs of genes that correlate significantly with latitude and altitude in African and European populations overlap with SNPs that correlate with a latitudinal cline from North America; (iii) at the genomewide level, the top candidate genes are enriched in gene ontology (GO) terms that are related to cold tolerance; (iv) GO enriched terms from North American clinal genes overlap significantly with those from Africa and Europe. Each SNP was tested in 10 independent runs of Bayenv2, using the median Bayes factors to ascertain candidate genes. None of the candidate genes were found close to the breakpoints of cosmopolitan inversions, and only four candidate genes were linked to QTLs related to CCRT. To overcome the limitation that we used only four populations to test correlations with environmental gradients, we performed simulations to estimate the power of our approach for detecting selection. Based on our results, we propose a novel network of genes that is involved in cold adaptation. PMID- 26558480 TI - Cytotoxic Glycosylated Fatty Acid Amides from a Stelletta sp. Marine Sponge. AB - We have discovered new glycosylated fatty acid amides, stellettosides, from a Stelletta sp. marine sponge. They were detected through LC-MS analysis of the extract combined with the cytotoxicity assay of the prefractionated sample. Their planar structures were determined by analyses of the NMR and tandem FABMS data. Stellettosides A1 and A2 (1 and 2) as well as stellettosides B1-B4 (3-6) were obtained as inseparable mixtures. Careful analysis of the NMR and tandem FABMS data of each mixture, along with comparison of the tandem FABMS data with that of a synthetic model compound, permitted us to assign the structure of the constituents in the mixture. The absolute configuration of the monosaccharide unit was determined by LC-MS after chiral derivatization. The relative configurations of the vicinal oxygenated methines in the fatty acid chains were assigned by the (1)H NMR data of the isopropylidene derivative. The mixture of stellettosides B1-B4 (3-6) exhibit moderate cytotoxic activity against HeLa cells with an IC50 value of 9 MUM, whereas the mixture of stellettosides A1 and A2 (1 and 2) was not active at a concentration of 10 MUM. PMID- 26558481 TI - Tuning Magnetic Relaxation in a Tb-Nitronyl Nitroxide Complex by Using Cocrystalline Paramagnetic Complex. AB - New 2p-4f and 2p-3d-4f compounds [Tb(hfac)3(NIT-PhNO2)2]. 0.5C7H16 (1) and [Ln(hfac)3(NIT-PhNO2)2]2[Cu(hfac)2(NIT-PhNO2)2] (Ln(III) = Gd 2, Tb 3; hfac = hexafluoroacetylacetonate; NIT-PhNO2 = 2-(p-nitrophenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide) have been obtained. Complex 1 consists of mononuclear trispin [Tb(hfac)3(NIT-PhNO2)2] units in which two radical ligands are ligated to the Tb(III) ion as monodentate ligands through the NO groups, while complexes 2 and 3 contain two kinds of trispin moieties, namely, [Ln(hfac)3(NIT-PhNO2)2] and [Cu(hfac)2(NIT-PhNO2)2]. In the [Cu(hfac)2(NIT PhNO2)2] moiety, the radicals are bonded to the copper(II) ion in the axial positions via the nitroxides. For three compounds, 1D supramolecular chains are formed via the pi-pi stacking interactions involving the radical ligands. Magnetic investigations show that both Tb complexes exhibit slow relaxation of magnetization at low temperature; strikingly, complex 3 displays a higher energy barrier than that of 1. It represents the first example to use the paramagnetic complex to tune magnetic relaxation of 4f-based compounds. PMID- 26558482 TI - Fragmentation of Cr(NO3)4(-): Metal Oxidation upon O(*-) Abstraction. AB - The decomposition of chromium nitrate anion, Cr(NO3)4(-), was investigated by tandem mass spectrometry. The major fragments correspond to sequential elimination of NO2(*) via O(*-) abstraction from each nitrate ligand to yield CrOn(NO3)(4-n)(-), n = 1-4, products. The metal is oxidized upon the first three O(*-) abstraction reactions to yield the fully oxidized Cr(VI), closed-shell, CrO3(NO3)(-) fragment. A CrO4(-) fragment was detected, but the metal is not further oxidized upon the fourth O(*-) abstraction. Experiment and theory indicate the first three O(*-) abstraction reactions are low energy processes, but the formation of CrO4(-) is considerably higher in energy. Theoretical studies show the 3d electrons in chromium are removed by O(*-) for CrOn(NO3)(4 n)(-), n = 1-3, to yield oxo, O(2-) ligands, but the electron density is replaced by donation from pi bonds involving the oxygen lone pairs. Theory predicts a decrease in metal charge for each O(*-) abstraction, opposite the trend expected for oxidation, due to pi electron donation from the oxygen atoms. PMID- 26558483 TI - Progress in understanding and utilizing TNF-alpha inhibition for the treatment of psoriatic arthritis. AB - The improved recognition of pathogenetic molecular mechanisms has led to the use of drugs targeting cytokines in different inflammatory arthropathies as well psoriatic arthritis (PsA). In particular, the progress in knowledge on tumor necrosis factor (TNF)-alpha in the pathogenesis of PsA has changed the therapeutic approach by use of direct and receptor cytokine antagonists. Currently, infliximab (IFX), adalimumab, etanercept, golimumab and certolizumab pegol represent the five anti-TNF-alpha available for the treatment of PsA. This review describes evidence on treatment aimed at neutralizing TNF-alpha in PsA patients, from the first study in 2000 until today, mainly derived from randomized clinical trials. In comparison with traditional therapies, anti-TNF alpha agents have shown to have more efficacy both in treating clinical aspects, including enthesitis, dactylitis, joint pain and swelling, axial involvement, nail and skin lesions, and in reducing radiographic progression. Moreover, anti TNF-alpha agents have been demonstrated to be reasonably safe in PsA, as confirmed by data derived by different registries. PMID- 26558484 TI - Assessment of Toxicity, Antifeedant Activity, and Biochemical Responses in Stored Grain Insects Exposed to Lethal and Sublethal Doses of Gaultheria procumbens L. Essential Oil. AB - The present study was undertaken to investigate the insecticidal activity of chemically characterized Gaultheria procumbens essential oil (EO) and its mode of action against the Coleopteran insects Sitophilus oryzae and Rhyzopertha dominica. Gas chromatography-mass spectrometry results depicted methyl salicylate (MS) as the major compound (96.61%) of EO. EO and its major compound methyl salicylate (MS) showed 100% mortality at 150 and 5.0 MUL/L air against S. oryzae and R. dominica, respectively, on 24 h of exposure. The in vivo percent inhibition of AChE activity ranged between 6.12 and 27.50%. In addition, changes in the antioxidative defense system, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and oxidized glutathione (GSSG), in test insects were estimated. A significant dose-dependent response in all test parameters was observed. The results demonstrated that G. procumbens EO could play a significant role in the formulation of EO-based insecticides for the management of stored grain insects. PMID- 26558485 TI - Biosynthetic Study on Antihypercholesterolemic Agent Phomoidride: General Biogenesis of Fungal Dimeric Anhydrides. AB - To elucidate the general biosynthetic pathway of fungal dimeric anhydrides, a gene cluster for the biosynthesis of the antihy-percholesterolemic agent phomoidride was identified by heterologous expression of candidate genes encoding the highly reducing polyketide synthase, alkylcitrate synthase (ACS), and alkylcitrate dehydratase (ACDH). An in vitro analysis of ACS and ACDH revealed that they give rise to anhydride monomers. Based on the established monomer biosynthesis, we propose a general biogenesis of dimeric anhydrides involving a single donor unit and four acceptor units. PMID- 26558486 TI - Flow Field Penetration in Thin Nanoporous Polymer Films under Laminar Flow by Forster Resonance Energy Transfer Coupled with Total Internal Reflectance Fluorescence Microscopy. AB - Polymer-fluid interfaces are used widely in a variety of applications, including separations, which require exposure of the polymer to dynamic flow conditions. Despite the ubiquity of such interfaces, the importance of convective mass transport within the near-interface region of a polymer is a fundamental process that is still poorly defined. As a step toward better defining mass transport behavior within the near-interface portion of a polymer, in this work, a new application of a spectroscopic method based on the combination of Forster resonance energy transfer (FRET) and total internal reflectance fluorescence microscopy (TIRFM) is reported that allows quantification of the penetration depth of a laminar flow field (i.e., the slip length) in a densely grafted, thin poly(N-isopropylacrylamide) (pNIPAM) film as a model polymer system. Specifically, decay curves from FRET of an acceptor with a donor attached at the substrate surface are fit to a combined Taylor-Aris-Fickian mass transport model to extract apparent linear diffusion coefficients of acceptor molecules for different flow rates. Apparent diffusion coefficients range from 1.9 * 10(-12) to 9.1 * 10(-12) cm(2)/s for near-surface flow linear velocities ranging from 192 to 2952 MUm/s. This increase in apparent diffusion coefficient with fluid flow rate suggests increasing contributions from convective mass transport that are indicative of flow field penetration into the polymer film. The depth of penetration of the flow field is estimated to range from ~6% of the polymer film thickness in a good solvent at ~192 MUm/s to ~60% of the film thickness at ~2952 MUm/s. Thus, flow field penetration into polymer thin films, with its concomitant contributions from convective mass transport within the near-interface region of the polymer, is demonstrated and quantified experimentally. PMID- 26558487 TI - Highly Stable Near-Infrared Fluorescent Organic Nanoparticles with a Large Stokes Shift for Noninvasive Long-Term Cellular Imaging. AB - Fluorescent organic nanoparticles based on small molecules have been regarded as promising candidates for bioimaging in recent years. In this study, we report a highly stable near-infrared (NIR) fluorescent organic nanoprobes based on nanoparticles of an anthraquinone derivate with strong aggregation-induced emission (AIE) characteristics and a large Stokes shift (>175 nm). These endow the nanoprobe with high fluorescent brightness and high signal-to-noise ratio. On the other hand, the nanoprobe also shows low cytotoxicity, good stability over a wide pH range, superior resistance against photodegradation and photobleaching comparing to typical commercial fluorescent organic dyes such as fluorescein sodium. Endowed with such merits in term of optical performance, biocompatibility, and stability, the nanoprobe is demonstrated to be an ideal fluorescent probe for noninvasive long-term cellular tracing and imaging applications. As an example, it is shown that strong red fluorescence from the nanoprobe can still be clearly observed in A549 human lung cancer cells after incubation for six generations over 15 days. PMID- 26558488 TI - Photopatterning of Hydrogel Microarrays in Closed Microchips. AB - To date, optical lithography has been extensively used for in situ patterning of hydrogel structures in a scale range from hundreds of microns to a few millimeters. The two main limitations which prevent smaller feature sizes of hydrogel structures are (1) the upper glass layer of a microchip maintains a large spacing (typically 525 MUm) between the photomask and hydrogel precursor, leading to diffraction of UV light at the edges of mask patterns, (2) diffusion of free radicals and monomers results in irregular polymerization near the illumination interface. In this work, we present a simple approach to enable the use of optical lithography to fabricate hydrogel arrays with a minimum feature size of 4 MUm inside closed microchips. To achieve this, we combined two different techniques. First, the upper glass layer of the microchip was thinned by mechanical polishing to reduce the spacing between the photomask and hydrogel precursor, and thereby the diffraction of UV light at the edges of mask patterns. The polishing process reduces the upper layer thickness from ~525 to ~100 MUm, and the mean surface roughness from 20 to 3 nm. Second, we developed an intermittent illumination technique consisting of short illumination periods followed by relatively longer dark periods, which decrease the diffusion of monomers. Combination of these two methods allows for fabrication of 0.4 * 10(6) sub-10 MUm sized hydrogel patterns over large areas (cm(2)) with high reproducibility (~98.5% patterning success). The patterning method is tested with two different types of photopolymerizing hydrogels: polyacrylamide and polyethylene glycol diacrylate. This method enables in situ fabrication of well defined hydrogel patterns and presents a simple approach to fabricate 3-D hydrogel matrices for biomolecule separation, biosensing, tissue engineering, and immobilized protein microarray applications. PMID- 26558489 TI - An overview of molecular fingerprint similarity search in virtual screening. AB - INTRODUCTION: A central premise of medicinal chemistry is that structurally similar molecules exhibit similar biological activities. Molecular fingerprints encode properties of small molecules and assess their similarities computationally through bit string comparisons. Based on the similarity to a biologically active template, molecular fingerprint methods allow for identifying additional compounds with a higher chance of displaying similar biological activities against the same target - a process commonly referred to as virtual screening (VS). AREAS COVERED: This article focuses on fingerprint similarity searches in the context of compound selection for enhancing hit sets, comparing compound decks, and VS. In addition, the authors discuss the application of fingerprints in predictive modeling. EXPERT OPINION: Fingerprint similarity search methods are especially useful in VS if only a few unrelated ligands are known for a given target and therefore more complex and information rich methods such as pharmacophore searches or structure-based design are not applicable. In addition, fingerprint methods are used in characterizing properties of compound collections such as chemical diversity, density in chemical space, and content of biologically active molecules (biodiversity). Such assessments are important for deciding what compounds to experimentally screen, to purchase, or to assemble in a virtual compound deck for in silico screening or de novo design. PMID- 26558490 TI - Promoting early exposure monitoring for respirable crystalline silica: Taking the laboratory to the mine site. AB - The exposure to respirable crystalline silica (RCS) in the mining industry is a recognized occupational hazard. The assessment and monitoring of the exposure to RCS is limited by two main factors: (1) variability of the silica percent in the mining dust and (2) lengthy off-site laboratory analysis of collected samples. The monitoring of respirable dust via traditional or real-time techniques is not adequate. A solution for on-site quantification of RCS in dust samples is being investigated by the Office of Mine Safety and Health Research, a division of the National Institute for Occupational Safety and Health. The use of portable Fourier transform infrared analyzers in conjunction with a direct-on-filter analysis approach is proposed. The progress made so far, the necessary steps in progress, and the application of the monitoring solution to a small data set is presented. When developed, the solution will allow operators to estimate RCS immediately after sampling, resulting in timelier monitoring of RCS for self assessment of compliance at the end of the shift, more effective engineering monitoring, and better evaluation of control technologies. PMID- 26558491 TI - The potential of function-led virtual environments for ecologically valid measures of executive function in experimental and clinical neuropsychology. AB - The assessment of executive functions is an integral task of neuropsychological assessment. Traditional measures of executive function are often based on hypothetical constructs that may have little relevance to real-world behaviours. In fact, some traditional tests utilised today were not originally developed for clinical use. Recently, researchers have been arguing for a new generation of "function-led" neuropsychological assessments that are developed from directly observable everyday behaviours. Although virtual environments (VEs) have been presented as potential aides in enhancing ecological validity, many were modelled on construct-driven approaches found in traditional assessments. In the current paper, we review construct-driven and function-led VE-based neuropsychological assessments of executive functions. Overall, function-led VEs best represent the sorts of tasks needed for enhanced ecological validity and prediction of real world functioning. PMID- 26558492 TI - Pharmacodynamic considerations in the treatment of pulmonary hypertension in infants: challenges and future perspectives. AB - INTRODUCTION: Pulmonary hypertension (PH) in infants is a life-threatening disease with a high mortality. It is treated with different drugs that act upon the three different pathways involved in its development. Studies on the drug pharmacodynamics are sparse, however. AREAS COVERED: This review reports a search on the currently available literature in English on drug pharmacodynamics in infants with PH. The search yielded 2499 citations in the EMBASE, MEDLINE, COCHRANE, Web of Science, PubMed Publisher and Google Scholar databases since 1961. Of these, 1691 did not meet the research question. Eventually, 655 articles were of interest, including 44 randomized controlled trials on PH in infants. These articles cover all PH medications used in infancy. EXPERT OPINION: Mortality of PH in infancy has dropped considerably over the past years. iNO is widely used, followed by sildenafil - both orally and intravenously in contrast to the exclusively oral use in adults. In adults, the pharmacodynamic effects of the different medications are tested using the 6-minute walking test, changes in the NYHA classification, or by invasive measurement of pulmonary pressure. Reliable data of pharmacodynamics tested in adequate series or in randomized controlled trials in children are lacking, however, for most of these medications. PMID- 26558493 TI - What next for newly diagnosed glioblastoma? AB - Glioblastoma is the most common primary brain tumor in adults. Despite current multimodality treatment including surgical resection and temozolomide-based chemoradiotherapy, median survival is only 14-16 months. Characterization of molecular alterations in glioblastoma has identified prognostic subgroups and therapeutic opportunities for clinical trials across glioblastoma subsets. Following a number of negative Phase III trials testing temozolomide dose intensification and angiogenesis inhibition, recent interim analysis data indicate survival prolongation with use of a device (OptuneTM) delivering alternating electrical field therapy in newly diagnosed glioblastoma patients. In this review, we present an overview of the data supporting the current standard of care and discuss novel experimental therapies in early and late phase clinical testing including devices, small molecule drugs, angiogenesis inhibitors, oncolytic virotherapy and immunotherapy. PMID- 26558494 TI - Light therapy for preventing seasonal affective disorder. AB - BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery (e.g. visors, light boxes) and form of light (e.g. bright white light) vary. OBJECTIVES: To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trails (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non randomised studies. We intended to include studies that compared any type of light therapy (e.g. bright white light, administered by visors or light boxes, infrared light, dawn stimulation) versus no treatment/placebo, second-generation antidepressants (SGAs), psychological therapies, melatonin, agomelatine, lifestyle changes, negative ion generators or another of the aforementioned light therapies. We also planned to include studies that looked at light therapy in combination with any comparator intervention and compared this with the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors independently abstracted data and assessed risk of bias of included studies. MAIN RESULTS: We identified 2986 citations after de duplication of search results. We excluded 2895 records during title and abstract review. We assessed 91 full-text papers for inclusion in the review, but only one study providing data from 46 people met our eligibility criteria. The included randomised controlled trial (RCT) had methodological limitations. We rated it as having high risk of performance and detection bias because of lack of blinding, and as having high risk of attrition bias because study authors did not report reasons for dropouts and did not integrate data from dropouts into the analysis.The included RCT compared preventive use of bright white light (2500 lux via visors), infrared light (0.18 lux via visors) and no light treatment. Overall, both forms of preventive light therapy reduced the incidence of SAD numerically compared with no light therapy. In all, 43% (6/14) of participants in the bright light group developed SAD, as well as 33% (5/15) in the infrared light group and 67% (6/9) in the non-treatment group. Bright light therapy reduced the risk of SAD incidence by 36%; however, the 95% confidence interval (CI) was very broad and included both possible effect sizes in favour of bright light therapy and those in favour of no light therapy (risk ratio (RR) 0.64, 95% CI 0.30 to 1.38). Infrared light reduced the risk of SAD by 50% compared with no light therapy, but in this case also the CI was too broad to allow precise estimations of effect size (RR 0.50, 95% CI 0.21 to 1.17). Comparison of both forms of preventive light therapy versus each other yielded similar rates of incidence of depressive episodes in both groups (RR 1.29, 95% CI 0.50 to 3.28). The quality of evidence for all outcomes was very low. Reasons for downgrading evidence quality included high risk of bias of the included study, imprecision and other limitations, such as self rating of outcomes, lack of checking of compliance throughout the study duration and insufficient reporting of participant characteristics.Investigators provided no information on adverse events. We could find no studies that compared light therapy versus other interventions of interest such as SGA, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Evidence on light therapy as preventive treatment for patients with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. PMID- 26558495 TI - Metabolism and health effects of phyto-estrogens. AB - Phyto-estrogens are plant-derived compounds that can exert various estrogenic and anti-estrogenic effects, and are usually used as a natural alternative to estrogen replacement due to their health benefits, including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Phyto estrogens are also considered as endocrine disruptors due to their structure similar to human female hormone 17-beta oestradiol. However, the issue of whether phyto-estrogens are beneficial or harmful to human health remains unknown, as this may depend on the dose, form, level and duration of administration of phyto estrogens, and influence by genetics, metabolism, gut physiology, age, diet, and the health status of individuals. Clarification on this issue is necessary for the sake of their two-side effects on human health and rapidly increasing global consumption of phyto-estrogens. This review mainly includes the metabolism of phyto-estrogens and weighs the evidence for and against the purported health benefits and adverse effects of phyto-estrogens. PMID- 26558496 TI - Resilience training in medical school: the solution to doctor burnout? PMID- 26558497 TI - Lactoperoxidase as a potential drug target. AB - INTRODUCTION: Lactoperoxidase (LPO) belongs to the immunologically relevant mammalian heme peroxidases. The enzyme contributes in external secretions to the humoral immune defense against pathogens by oxidation of thiocyanate (SCN(-)) and iodide (I(-)). The generation of oxidized thiocyanate and/or iodine species is also important in numerous biotechnological applications of LPO. AREAS COVERED: In this review, we give an overview about the present knowledge of LPO concerning enzymatic structure, catalytic cycles and (pseudo-)halogenated species generated by the enzyme. Redox properties of LPO as well as kinetic aspects regarding the different enzymatic cycles are discussed in order to gain insights into the disturbance of the (pseudo-)halogenating enzyme activity under pathological conditions. Important structural features of LPO and crystallographic studies on the interaction and reaction of organic substrates with the enzyme are also summarized. A broad discussion is devoted to the binding and oxidation of substrates that either inhibit or promote LPO activity. EXPERT OPINION: On the basis of these data, different strategies to further optimize LPO functions in humoral defense of mucous surfaces and biotechnological applications are discussed. In particular, hydrophobic organic substrates with a 3,4 dihydroxyphenyl partial structure considerably enhance the (pseudo-)halogenating activity of LPO. Their application provides, thus, a new strategy to enhance the anti-microbial activity of this enzyme. PMID- 26558498 TI - Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy. AB - Tumor immunotherapy is emerging as a promising new treatment option for patients with cancer. T-VEC is an intralesional oncolytic virus therapy based on a modified herpes simplex virus type-1. T-VEC selectively targets tumor cells, causing regression in injected lesions and inducing immunologic responses that mediate regression at uninjected/distant sites. In a randomized phase III trial, T-VEC met its primary endpoint of improving the durable response rate vs granulocyte-macrophage colony-stimulating factor in patients with unresectable melanoma. Responses were observed in injected and uninjected regional and visceral lesions. Exploratory analyses suggested survival differences in favor of T-VEC in patients with untreated or stage IIIB/IIIC/IVM1a disease. T-VEC was generally well tolerated, the most common adverse events being flu-like symptoms. Here, we overview recent advances in cancer immunotherapy, focusing on the clinical development of T-VEC, from first-in-human studies and studies in other cancer types, to ongoing combination trials with checkpoint inhibitors. PMID- 26558499 TI - Posttraumatic Stress Disorder's Underlying Dimensions and Their Relation With Impulsivity Facets. AB - Research indicates a significant relationship between posttraumatic stress disorder (PTSD) and impulsivity (Kotler, Julian, Efront, and Amir, J Nerv Ment Dis 189:162-167, 2001; Ledgerwood and Petry, J Trauma Stress 19:411-416, 2006). The present study assessed relations between PTSD symptom clusters and impulsivity subscales in an effort to assess the specific impulsivity component most related to PTSD's alterations in arousal/reactivity and alterations in mood/cognitions symptoms. In the current study, the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, and the UPPS Impulsivity Scale were administered to a sample of 412 nonclinical subjects with a trauma history. Results indicated that PTSD's alterations in arousal/reactivity and mood/cognition factors were most related to impulsivity's sensation-seeking tendency compared with other impulsivity components. Results highlight the importance of assessing and addressing (1) sensation-seeking tendencies and (2) urges to act impulsively when experiencing negative affect in trauma treatment. Furthermore, it is possible that sensation-seeking tendencies are primarily driving the comorbidity between PTSD and certain impulsive behaviors. PMID- 26558500 TI - Among Inpatients, Posttraumatic Stress Disorder Symptom Severity Is Negatively Associated With Time Spent Walking. AB - This study aimed to determine whether posttraumatic stress disorder (PTSD) symptom severity and psychological and functional variables were associated with physical activity (PA) upon admission to an inpatient facility. PTSD symptoms, depression, anxiety and stress, sleep quality, and PA participation were assessed among 76 participants (age, 47.6 +/- 11.9 years; 83% male). Backward stepwise regression analyses identified variables independently associated with time spent walking and engaging in moderate-vigorous PA (MVPA). No significant correlations were found between any of the variables and MVPA. Total PTSD symptoms (r = -0.39, p < 0.001), combined symptoms of depression, anxiety, and stress (r = -0.31, p < 0.01), and sleep behavior (r = -0.24, p < 0.05) were significantly and negatively associated with total walking time. Total PTSD symptoms were the only significant predictor of walking time (B = -0.03, SE = 0.008, beta = -0.4; t = -3.4; p < 0.001). Results indicate that increased PTSD symptoms are associated with lower levels of walking. Results highlight the importance of considering symptoms when designing PA programs for people with PTSD. PMID- 26558501 TI - Type D Personality and Essential Hypertension in Primary Care: A Cross-Sectional Observational Study Within a Cohort of Patients Visiting General Practitioners. AB - To estimate the relationship between type D personality and essential hypertension among patients visiting their GPs for any health problem, 101 hypertensive and 138 nonhypertensive patients were consecutively recruited and assessed using the Type D Personality Scale (DS14). The predictive value of type D personality was determined using a logistic regression model, taking into account the differences in recognized confounders between groups. Type D personality in the hypertension group was twice as frequent as in the no hypertension group and hypertension was more frequent among type D than non-type D patients. Logistic regression showed a significant predictive value of type D personality for hypertension, adjusting for sex, age, body mass index, family history of hypertension, living condition, education, and employment. Therefore, type D personality was strongly related to hypertension and it was a noteworthy predictor of hypertension in a real-world cohort of primary care patients. PMID- 26558502 TI - Integrated Care and the Behavioral Health Home: A New Program to Help Improve Somatic Health Outcomes for Those With Serious Mental Illness. AB - Research indicates that individuals with serious mental illness (SMI) consistently have lower access to primary care and much higher rates of preventable somatic health problems, like diabetes, hypertension, and hyperlipidemia. These higher rates of preventable somatic health problems result in poorer quality of life, lower life expectancy, and higher use of expensive emergency care. With this growing awareness and the recent health care reform, a new program, called the Behavioral Health Home (BHH), has been created to reduce barriers that individuals with SMI face when trying to access primary care. This report provides information on the how these health disparities were well documented at a university-based psychiatric clinical program and the creation of a BHH to help address these health needs. Lessons learned from initial implementation and future directions of the BHH are discussed. PMID- 26558503 TI - A Model for Recruiting Clinical Research Participants With Anxiety Disorders in the Absence of Service Provision: Visions, Challenges, and Norms Within a Canadian Context. AB - High-quality research in clinical psychology often depends on recruiting adequate samples of clinical participants with formally diagnosed difficulties. This challenge is readily met within the context of a large treatment center, but many clinical researchers work in academic settings that do not feature a medical school, hospital connections, or an in-house clinic. This article describes the model we developed at the University of Waterloo Centre for Mental Health Research for identifying and recruiting large samples of people from local communities with diagnosable mental health problems who are willing to participate in research but for whom treatment services are not offered. We compare the diagnostic composition, symptom profile, and demographic characteristics of our participants with treatment-seeking samples recruited from large Canadian and American treatment centers. We conclude that the Anxiety Studies Division model represents a viable and valuable method for recruiting clinical participants from the community for psychopathology research. PMID- 26558504 TI - The role of lncRNAs in hepatocellular carcinoma: opportunities as novel targets for pharmacological intervention. AB - Long non-coding RNA (lncRNA) is commonly defined as an RNA with a length of greater than 200 nucleotides, frequently up to 100 kb. Numerous studies have shown that dysregulation of lncRNAs may directly relate to a number of human diseases, particularly in oncology where lncRNAs appear to play an important role. LncRNAs may also play a potentially novel and critical role in the development and progression of hepatocellular carcinoma (HCC). This article discusses lncRNAs as a new possibility for diagnostic and therapeutic approaches for HCC. The authors introduce the relationship between some lncRNAs and HCC, including carcinogenesis, development, metastasis and prognosis. In addition, the authors suggest that the discovery of lncRNAs may encourage the discovery and development of new therapeutic modalities for HCC and that their regulation may be a promising potential treatment for HCC. Clinical studies are required to determine the therapeutic effect of regulating lncRNA in humans with HCC. PMID- 26558505 TI - Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate. AB - Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged <=18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Delta creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Delta creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Delta creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Delta creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Delta creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Delta creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance. PMID- 26558506 TI - Clinical implications of recent findings in schistosome proteomics. AB - Schistosomiasis is a neglected tropical disease of clinical significance that, despite years of research, still requires an effective vaccine and improved diagnostics for surveillance, control and potential elimination. Furthermore, the causes of host pathology during schistosomiasis are still not completely understood. The recent sequencing of the genomes of the three key schistosome species has enabled the discovery of many new possible vaccine and drug targets, as well as diagnostic biomarkers, using high-throughput and sensitive proteomics methods. This review focuses on the literature of the last 5 years that has reported on the use of proteomics to both better understand the biology of the schistosome parasites and the disease they cause in definitive mammalian hosts. PMID- 26558507 TI - Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindoles. AB - The synthesis of polysubstituted hexahydroindoles through trienamine organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium catalyzed cycloisomerization, is reported. The cycloadditions of this novel class of dienals proceed with excellent levels of enantio- and diastereoselectivity, with the regioselectivity of cycloaddition with respect to the tethering ring readily tuned through design of the cycloisomerization substrate. This work culminates in the first examples of double-stereodifferentiating trienamine catalysis, where catalyst stereocontrol dominates facial selectivity in the cycloaddition, affording azacyclic products that are specifically functionalized at every position. PMID- 26558509 TI - A population-based analysis of use and outcomes of laparoscopic bariatric surgery across socioeconomic groups in Taiwan. AB - BACKGROUND: With the growing development of minimally invasive techniques for the treatment of morbid obesity, laparoscopic bariatric surgery (LBS) is increasingly performed. This study aimed to assess the association between patients' socioeconomic status (SES) and the likelihood of undergoing LBS and related outcomes in Taiwan. METHODS: This nationwide population-based study was conducted by using data from Taiwan's National Health Insurance Research Database. A total of 3678 morbidly obese patients aged 18 years and older who underwent conventional open bariatric surgery or LBS were identified between 2004 and 2011. Regression analyses were performed using generalized estimating equation (GEE) models to account for the nesting of patients within physician to assess patients' SES category associated with the use of LBS and related outcomes. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated. RESULTS: Compared with those with medium and low SES (84.6 % and 80.2 %), patients with high SES (88.1 %) had the highest percentage of undergoing LBS (P < 0.001). After adjusting for patient demographics, institution and surgeon characteristics, the multivariate GEE analysis revealed that the highest likelihood of undergoing LBS was noted in morbidly obese patients with high SES (OR = 1.45, 95 % CI 1.10 1.90), followed by those with medium SES (OR = 1.27, 95 % CI 1.04-1.56). In addition, patients with high SES had slightly lower length of hospital stay (LOS; OR = 0.90, 95 % CI 0.82-0.99) and hospital treatment cost (OR = 0.93, 95 % CI 0.87-0.99) than their counterparts after adjustment. CONCLUSIONS: The increased likelihood of undergoing LBS and lower LOS and hospital treatment cost were noted among morbidly obese patients with higher SES. This finding suggests there is the need to improve clinical practice and reduce health disparities in the surgical treatment of morbidly obese patients. PMID- 26558510 TI - Extracurricular activity participation moderates impact of family and school factors on adolescents' disruptive behavioural problems. AB - BACKGROUND: The prevalence of problem behaviours among British adolescents has increased in the past decades. Following Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model, it was hypothesized that youth problem behaviour is shaped in part by social environment. The aim of this project was to explore potential protective factors within the social environment of British youth's for the presentation of disruptive behavioural problems. METHOD: This study used secondary data from the Longitudinal Study of Young People in England, a cohort study of secondary school students. These data were analysed with generalized estimation equations to take the correlation between the longitudinal observations into account. Three models were built. The first model determined the effect of family, school, and extracurricular setting on presentation of disruptive behavioural problems. The second model expanded the first model by assuming extracurricular activities as protective factors that moderated the interaction between family and school factors with disruptive behavioural problems. The third model described the effect of prior disruptive behaviour on current disruptive behaviour. RESULTS: Associations were found between school factors, family factors, involvement in extracurricular activities and presence of disruptive behavioural problems. Results from the second generalized estimating equation (GEE) logistic regression models indicated that extracurricular activities buffered the impact of school and family factors on the presence of disruptive behavioural problems. For instance, participation in sports activities decreased the effect of bullying on psychological distress. Results from the third model indicated that prior acts of disruptive behaviour reinforced current disruptive behaviour. CONCLUSION: This study supports Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model; social environment did influence the presence of disruptive behavioural problems for British adolescents. The potential of extracurricular activities to intervention strategies addressing disruptive behavioural problems of adolescents is discussed. PMID- 26558511 TI - In vitro response of date palm (Phoenix dactylifera L.) to K/Na ratio under saline conditions. AB - BACKGROUND: Salinity is a serious factor limiting the productivity of agricultural plants. One of the potential problems for plants growing under saline conditions is the inability to up take enough K(+). The addition of K(+) may considerably improve the salt tolerance of plants grown under salinity. It is assumed that increasing the K(+) supply at the root zone can ameliorate the reduction in growth imposed by high salinity. The present study aims to determine whether an increase in the K/Na ratio in the external media would enhance the growth of date palm seedlings under in vitro saline conditions. METHODS: Date palm plants were grown at four concentrations of Na + K/Cl (mol/m(3)) with three different K/Na ratios. The 12 salt treatments were added to modified MS medium. The modified MS medium was further supplemented with sucrose at 30 g/l. RESULTS: Growth decreased substantially with increasing salinity. Growth expressed as shoot and root weight, enhanced significantly with certain K/Na ratios, and higher weight was maintained in the presence of equal K and Na. It is the leaf length, leaf thickness and root thickness that had significant contribution on total dry weight. Na(+) contents in leaf and root increased significantly increased with increasing salinity but substantial decreases in Na(+) contents were observed in the leaf and root with certain K/Na ratios. This could be attributed to the presence of a high K(+) concentration in the media. The internal Na(+) concentration was higher in the roots in all treatments, which might indicate a mechanism excluding Na(+) from the leaves and its retention in the roots. K/Na ratios up to one significantly increased the leaf and root K(+) concentration, and it was most pronounced in leaves. The K(+) contents in leaf and root was not proportional to the K(+) increase in the media, showing a high affinity for K(+) uptake at lower external K(+) concentrations, but this mechanism continues to operate even with high external Na(+) concentrations. CONCLUSION: Increasing K/Na ratios in the growing media of date plam significantly reduced the absorption of Na(+) less than 200 mM and also balance ions compartmentalization. PMID- 26558512 TI - Changes in circulating lipids level over time after acquiring HCV infection: results from ERCHIVES. AB - BACKGROUND: Changes in lipid levels over time after acquiring HCV infection, and how they differ from HCV-uninfected persons are unknown. METHODS: We used ERCHIVES to identify those with a known HCV seroconversion window and persistently negative controls. We excluded subjects with HIV and hepatitis B and those who received lipid lowering agents. Total Cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG) and non HDL cholesterol were retrieved at yearly intervals and plotted over time. RESULTS: Among 1,270 HCV+ and 5,070 HCV- subjects, median age [IQR] was 47[37,53] for HCV+ and 52[47,57] for the HCV- group; 69% were White and 91% were males in each group. Mean BMI [SD] was 26.94[6.73] in the HCV+ and 28.15 [5.98] in the HCV group (P < 0.001). Over a 10-year follow-up period among HCV+ persons, TC decreased by (mean (SD) mg/dL) 12.06(36.95), LDL by 9.22(31.44), TG by 13.58(87.01) and non-HDL-C by 12.55(35.14). Among HCV- persons, TC cholesterol decreased by 4.15(31.21), LDL by 4.16(26.51); TG by 4.42(82.34) and non-HDL-C by 5.78(30.17). CONCLUSIONS: After HCV acquisition, TC, LDL, TG and non-HDL-C progressively decline over time independent of BMI and liver fibrosis. Consequences of lipid changes and the need and optimal timing of lipid lowering therapy in HCV+ persons require further study. PMID- 26558513 TI - Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. AB - INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome. METHODS: We searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality. RESULTS: Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose. CONCLUSION: PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late. PMID- 26558514 TI - Quantification of antimicrobial usage in dairy cows and preweaned calves in Argentina. AB - Antimicrobials are commonly used to treat diseases in dairy cows and in calves. In Argentina information about veterinary antimicrobial usage at herd level is still limited. The purpose of this study was to quantify antimicrobial usage at herd level of most used drugs to treat lactating cows (LC) and preweaned calves (PWC). Prevalence of diseases and antimicrobial drug usage in 18 milking herds and in 11 calves rearing units (CRUs) were assessed through a survey. Drug usage (DU) at herd level was estimated through a standardized indicator, the number of Defined Daily Doses Animal (DDDA) per year, considering a standardized body weight of 600kg for LC and of 60kg for PWC. Pearson correlation coefficients were estimated and used to evaluate the association of LC herd size and milk yield (kg/day) with each disease prevalence and with DU. Student t-Test was used to compare disease prevalence and DU with various management practices in CRUs. Clinical mastitis was the most prevalent disease followed by foot, uterine and respiratory diseases in adult dairy cows. More involvement of veterinarians in treatment decisions was observed in larger dairy herds. Most used antimicrobials were beta-lactams and aminoglycosides. Especially for intramammary compounds, there was a trend towards multidrug formulations. The median DU was 5.21 DDDA/LC/year (range=2.88-10.88), the intramammary usage for clinical mastitis (IM CM) and dry cow therapy (IM-DRY), representing 85.4% of total drug usage. No significant correlations were observed between herd size or milk yield with disease prevalence and with DU for all considered uses (IM-CM, IM-DRY and parental (PAR)). Enteritis was reported in all CRUs, followed by respiratory disease (91%), and omphalophlebitis (3%). The median DU for all drugs used at CRU level was 0.49 DDDA/PWC/year. Prevalences and DU for treatment of enteritis and respiratory diseases did not differ significantly between rearing systems, colostrum management or permanence time of the calf with the mother after birth. Although it was possible to estimate the drug usage at farm level, it was observed that the diversity of drug compounds and dose heterogeneity presented by the various manufacturers made the calculation of those indicators complex. PMID- 26558515 TI - Synthesis of di- and tri-saccharide fragments of Salmonella typhi Vi capsular polysaccharide and their zwitterionic analogues. AB - Zwitterionic polysaccharides (ZPS) behave like traditional T cell-dependent antigens, suggesting the design of new classes of vaccines alternative to currently used glycoconjugates and based on the artificial introduction of a zwitterionic charge motif onto the carbohydrate structure of pathogen antigens. Here we report the new synthesis and antigenic evaluation of di-/tri-saccharide fragments of Salmonella typhi Vi polysaccharide, as well as of their corresponding zwitterionic analogues. Our strategy is based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. The effect of structural modifications of the synthetic compounds on antigenic properties was evaluated by competitive ELISA. All the oligosaccharides were recognized by specific anti-Vi polyclonal antibodies in a concentration-dependent manner, and the introduction of a zwitterionic motif into the synthetic molecules did not prevent the binding. PMID- 26558516 TI - Design, synthesis and preliminary bioactivity studies of imidazolidine-2,4-dione derivatives as Bcl-2 inhibitors. AB - Anti-apoptotic B-cell lymphoma-2 (Bcl-2) proteins are promising targets for cancer therapy. In the present study, a series of imidazolidine-2,4-dione derivatives were designed and synthesized to test their inhibitory activities against anti-apoptotic Bcl-2 proteins. Among them, compound 8k had better growth inhibitory effects on K562 and PC-3 cell lines compared to lead compound WL-276. PMID- 26558517 TI - Helical peptide-polyamine and -polyether conjugates as synthetic ionophores. AB - Two new synthetic ionophores in which the hydrophobic portion is represented by a short helical Aib-peptide (Aib=alpha-amino-isobutyric acid) and the hydrophilic one is a poly-amino (1a) or a polyether (1b) chain have been prepared. The two conjugates show a high ionophoric activity in phospholipid membranes being able to efficiently dissipate a pH gradient and, in the case of 1b, to transport Na(+) across the membrane. Bioactivity evaluation of the two conjugates shows that 1a has a moderate antimicrobial activity against a broad spectrum of microorganisms and it is able to permeabilize the inner and the outer membrane of Escherichia coli cells. PMID- 26558518 TI - Synthesis and biological profiling of 6- or 7-(het)aryl-7-deazapurine 4'-C methylribonucleosides. AB - The synthesis and biological activity profiling of a large series of diverse pyrrolo[2,3-d]pyrimidine 4'-C-methylribonucleosides bearing an (het)aryl group at position 4 or 5 is reported as well as the synthesis of several phosphoramidate prodrugs. These compounds are 4'-C-methyl derivatives of previously reported cytostatic hetaryl-7-deazapurine ribonucleosides. The synthesis is based on glycosylation of halogenated 7-deazapurine bases with 1,2-di-O-acetyl-3,5-di-O benzyl-4-C-methyl-beta-d-ribofuranose followed by cross-coupling and nucleophilic substitution reactions. The final compounds showed low cytotoxicity and several derivatives exerted antiviral activity against HCV or Dengue viruses at micromolar concentrations. PMID- 26558519 TI - Intracerebral Hemorrhage In Anticoagulated Patients: Evidence-Based Emergency Department Management. AB - Spontaneous intracerebral hemorrhage is a true neurological emergency, and its management is made more complicated when patients are anticoagulated, as reversal of anticoagulation must be initiated simultaneously with diagnosis, treatment, and disposition. Recent advances such as newer laboratory testing and rapid computed tomography for diagnosis, blood pressure reduction to reduce hematoma expansion, and new anticoagulant reversal agents may allow for improved outcomes. Management of intracranial pressure is particularly important in anticoagulated patients, as is identifying patients who may benefit from rapid neurosurgical intervention and/or emergent transport to facilities capable of managing this disease. PMID- 26558520 TI - [Congenital neck mass. Diagnosis and treatment]. AB - Congenital neck masses are a challenge for general practitioners and specialists. Although some of them are diagnosed in utero, most of them remain silent until complications appear in the adult age. The anatomical location, consistency and age are determinants in guiding the possible diagnosis. A midline infrahyoid mass may be a thyroglossal cyst, however a lateral neck mass is more possible to result in a brachial cyst. Complementary imaging studies are essential such as pathological tests like needle aspiration fine needle aspiration (FNA). PMID- 26558521 TI - Crystallization and precipitation of phosphate from swine wastewater by magnesium metal corrosion. AB - This paper presents a unique approach for magnesium dosage in struvite precipitation by Mg metal corrosion. The experimental results showed that using an air bubbling column filled with Mg metal and graphite pellets for the magnesium dosage was the optimal operation mode, which could significantly accelerate the corrosion of the Mg metal pellets due to the presence of graphite granules. The reaction mechanism experiments revealed that the solution pH could be used as the indicator for struvite crystallization by the process. Increases in the Mg metal dosage, mass ratio of graphite and magnesium metal (G:M) and airflow rate could rapidly increase the solution pH. When all three conditions were at 10 g L(-1), 1:1 and 1 L min(-1), respectively, the phosphate recovery efficiency reached 97.5%. To achieve a high level of automation for the phosphate recovery process, a continuous-flow reactor immersed with the graphite-magnesium air bubbling column was designed to harvest the phosphate from actual swine wastewater. Under conditions of intermittently supplementing small amounts of Mg metal pellets, approximately 95% of the phosphate could be stably recovered as struvite of 95.8% (+/-0.5) purity. An economic analysis indicated that the process proposed was technically simple and economically feasible. PMID- 26558522 TI - Ischemic Injury of the Papillomacular Bundle Is a Predictive Marker of Poor Vision in Eyes With Branch Retinal Artery Occlusion. AB - PURPOSE: To propose a novel prognostic feature of spectral-domain optical coherence tomography (SDOCT) in macula-involving branch retinal artery occlusion (BRAO). DESIGN: Retrospective comparative case study. METHODS: We analyzed 66 eyes diagnosed with acute BRAO involving the macula from our hospital RAO registry. At presentation, a detailed ophthalmic and medical history was obtained from all patients, and all underwent a comprehensive ophthalmic evaluation, which included visual acuity examination, fundus photography, fluorescein angiography, and SDOCT. This evaluation was performed at each follow-up visit. RESULTS: The 66 eyes diagnosed with acute BRAO involving the macula were divided into 2 groups according to initial vision: Good Vision (>=20/40, 29 eyes, 44%) and Poor Vision (<20/40, 37 eyes, 56%). The Poor Vision group was further divided into Improvement (18 eyes, 27%) and Nonimprovement (19 eyes, 28%) groups, according to visual recovery at the final examination. Among multiple OCT parameters, the involvement of papillomacular bundle, but not that of the central fovea, was consistently observed in the Poor Vision group (P < .001) and more significantly in the Nonimprovement group (P < .001). Papillomacular bundle involvement features included signs of inner retinal ischemia, including inner retinal thickening, inner retinal hyperreflectivity, and loss of layer-by-layer integrity. Loss of layer-by-layer integrity was seen consistently in the Nonimprovement group. Quantitative analysis of inner retinal thickness also supported this association. CONCLUSION: In eyes with macula-involving BRAO, ischemic injury of the papillomacular bundle at the acute stage, as seen on OCT, correlates closely with poor vision and can explain the poor visual prognosis. PMID- 26558523 TI - Outcomes of Repeat Keratoplasty for Failed Therapeutic Keratoplasty. AB - PURPOSE: To analyze clinical outcomes of repeat optical penetrating (PK) or endothelial keratoplasty (EK) after failed therapeutic keratoplasty (TPK). DESIGN: Retrospective consecutive, comparative, interventional case series. METHODS: setting: LV Prasad Eye Institute, Hyderabad, India. STUDY POPULATION: Patients aged >18 years who underwent a repeat PK or EK following a failed TPK with a follow-up of at least 1 year were included. Patients with culture-negative ulcers, viral etiology, coexistent ocular surface disease, and multiple grafts were excluded from the study. INTERVENTION: PK or EK for failed TPK. MAIN OUTCOME MEASURE: Corrected distance visual acuity at 1 year follow-up. secondary outcome measure: Graft clarity. RESULTS: One hundred twelve eyes (67 PK, 45 EK) were included in the study. The PK group had a significantly higher number of cases with high-risk features prior to regraft. Improvement in visual acuity in each of the types of grafts was statistically significant (P < .01), but there was no difference between the 2 groups at 1 year postoperatively. A statistically significant proportion of grafts regained graft clarity after regrafting in the PK group (P < .01) but not in the EK group (P = .205) at 1 year postoperatively. Endothelial rejection rates were higher in the PK group. Subgroup analysis showed that eyes that had PK or EK for failed TPK conducted for Aspergillus keratitis showed better outcomes in terms of graft clarity. Kaplan-Maier (KM) survival analysis for graft clarity showed cumulative survival of 50% at 5 years. The survival using the KM curve was not statistically different between the 2 groups (P = .33). CONCLUSION: This study shows that visual rehabilitation with relatively good functional outcomes can be achieved by performing repeat PK or EK in patients after failed TPK. PMID- 26558524 TI - Neoadjuvant Systemic Therapy Before Radical Prostatectomy in High-Risk Prostate Cancer Does Not Increase Surgical Morbidity: Contemporary Results Using the Clavien System. AB - BACKGROUND: Multimodality therapies for men with high- and very high-risk prostate cancer, including neoadjuvant systemic therapy followed by subsequent radical prostatectomy (RP) are being increasingly explored despite the lack of adequate morbidity data. MATERIALS AND METHODS: We analyzed the data from 215 consecutive patients with high- and very high-risk prostate cancer who were previously untreated or had received neoadjuvant systemic therapy. All patients underwent RP with extended pelvic lymph node dissection from 2006 to 2010 at a single tertiary care academic center. All complications within 90 days of surgery were defined and categorized by a 5-grade and 10-domain modification of the Clavien system. Univariable and multivariable logistic regression analyses were used to identify preoperative predictors for complications. RESULTS: Of the 215 patients, 29% experienced a complication of any grade <= 90 days after surgery; 6% experienced grade >= 3, with no significant difference between either cohort (P = .50). On multivariate analysis, open RP (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.11-3.90; P = .02) and preoperative hemoglobin (OR, 1.98; 95% CI, 1.05-3.72; P = .03) were independent predictors of the occurrence of any grade complication. For major complications (Clavien >= 3), a Charlson comorbidity index of 6 to 7 versus 3 to 5 (OR, 5.45; 95% CI, 1.57-18.98; P = .008) and the most recent year of surgery (OR, 4.73; 95% CI, 1.36-16.39; P = .01) were significant predictors on multivariable analysis. CONCLUSION: The use of neoadjuvant systemic therapy did not appear to increase the risk of perioperative complications. These findings support current clinical trials, which might elucidate the oncologic benefit of this multimodality approach. PMID- 26558525 TI - VEGF Gene Polymorphisms are Associated with Risk of Tetralogy of Fallot. AB - BACKGROUND: The aim of this study was to investigate associations of 3 common polymorphisms in the VEGF gene, -2578C>A, -634C>G, and 936C>T, with risk of tetralogy of Fallot (TOF) in Chinese Han children. MATERIAL AND METHODS: From January 2010 to June 2013, a total of 400 pediatric subjects were recruited, including 160 cases with TOF (TOF group) and 240 healthy controls (control group). The genotypes of 3 common VEGF polymorphisms, -2578C>A, -634C>G, and 936C>T, were analyzed by polymerase chain reaction restriction fragment length polymorphism. All data were analyzed with SPSS 18.0 software. RESULTS: No significant differences were observed in body mass index or sex between TOF patients and controls (both P>0.05), but significant differences in age and family history of TOF were observed between the 2 groups (both P<0.05). The AA genotype in -2578C>A of VEGF was correlated with a significantly increased risk of TOF, and TOF risk in A allele carrier was 1.54-fold higher than that of C allele carrier (OR=1.54, 95%CI=1.14-2.09, P=0.005); the statistical significance was still present after Bonferroni correction (Pc=0.045). GG genotype in -634C>G of VEGF gene was also associated with an increased risk of TOF, and TOF risk in patients with G allele was 1.62-fold higher compared to patients with C allele (OR=1.62, 95%CI=1.19-2.21, P=0.002); the statistical significance was still present after Bonferroni correction (Pc=0.018). Interestingly, T allele in VEGF 936C>T polymorphism is associated with a decreased TOF risk (OR=0.65, 95%CI=0.49 0.87, P=0.003, the statistical significance was still present after Bonferroni correction (Pc=0.027). The result of logistic regression analysis revealed that 2578C>A, -634C>G, and 936C>T genotypes are independently related to the prevalence of TOF (all P<0.05). CONCLUSIONS: Our results confirmed that VEGF genetic polymorphisms, -2578C>A and -634C>G, may be associated with an increased TOF risk, while 936C>T polymorphism may be associated with decreased TOF risk. PMID- 26558526 TI - Surgical resection and peri-operative chemotherapy for colorectal cancer liver metastases: A population-based study. AB - BACKGROUND: Most literature describing surgery for colorectal cancer (CRC) liver metastases (LM) comes from high volume centres. Here, we report management and outcomes achieved in routine clinical practice. METHODS: All cases of CRC in Ontario who underwent resection of LM in 1994-2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified chemotherapy delivery. Temporal trends are described for 3 periods: 1994-1999, 2000-2004, 2005-2009. We describe volume of resected CRCLM as a ratio of incident cases per CRCLM resection. Overall (OS) and cancer-specific survival (CSS) are measured from time of LM resection. RESULTS: 2717 patients underwent resection of CRCLM. Between 1994 and 2009 there was a 78% increase in case volume; from one resection for every 48 incident cases to one resection for every 27 incident cases, p < 0.001. Use of peri-operative chemotherapy increased over study periods from 44% (306/700), to 52% (429/830), to 65% (777/1187, p < 0.001). Chemotherapy utilization rates varied across geographic regions (range 43%-69%, p < 0.001). Post-operative mortality rates at 30 and 90 days were 2.5% and 4.3% respectively. Five year OS during the study periods was 36% (95% CI 32-39%), 40% (95% CI 36 43%), and 46% (95% CI 43-49%) (p < 0.001); CSS was 38% (95% CI 35-42%), 42% (95% CI 38-45%), 49% (95% CI 44-53%) (p < 0.001). The temporal improvement in OS/CSS persisted on adjusted analyses. CONCLUSIONS: Outcomes of patients with resected CRCLM in routine practice is comparable to those reported from high volume centres. Survival improved over the study period despite a greater proportion of patients with CRC undergoing liver resection. PMID- 26558527 TI - Contrast coding in the electrosensory system: parallels with visual computation. AB - To identify and interact with moving objects, including other members of the same species, an animal's nervous system must correctly interpret patterns of contrast in the physical signals (such as light or sound) that it receives from the environment. In weakly electric fish, the motion of objects in the environment and social interactions with other fish create complex patterns of contrast in the electric fields that they produce and detect. These contrast patterns can extend widely over space and time and represent a multitude of relevant features, as is also true for other sensory systems. Mounting evidence suggests that the computational principles underlying contrast coding in electrosensory neural networks are conserved elements of spatiotemporal processing that show strong parallels with the vertebrate visual system. PMID- 26558528 TI - Delayed postpartum hemorrhage by traumatic lesion of uterine vessel without pseudo-aneurysm. PMID- 26558529 TI - Single cell analysis of cancer cells using an improved RT-MLPA method has potential for cancer diagnosis and monitoring. AB - Single cell analysis techniques have great potential in the cancer genomics field. The detection and characterization of circulating tumour cells are important for identifying metastatic disease at an early stage and monitoring it. This protocol is based on transcript profiling using Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (RT-MLPA), which is a specific method for simultaneous detection of multiple mRNA transcripts. Because of the small amount of (circulating) tumour cells, a pre-amplification reaction is performed after reverse transcription to generate a sufficient number of target molecules for the MLPA reaction. We designed a highly sensitive method for detecting and quantifying a panel of seven genes whose expression patterns are associated with breast cancer, and optimized the method for single cell analysis. For detection we used a fluorescence-dependent semi-quantitative method involving hybridization of unique barcodes to an array. We evaluated the method using three human breast cancer cell lines and identified specific gene expression profiles for each line. Furthermore, we applied the method to single cells and confirmed the heterogeneity of a cell population. Successful gene detection from cancer cells in human blood from metastatic breast cancer patients supports the use of RT-MLPA as a diagnostic tool for cancer genomics. PMID- 26558530 TI - A Telephone-Based Program to Provide Symptom Monitoring Alone vs Symptom Monitoring Plus Care Management for Late-Life Depression and Anxiety: A Randomized Clinical Trial. AB - IMPORTANCE: Mental health (MH) conditions are undertreated in late life. It is important to identify treatment strategies that address variability in treatment content and delivery and take individual-specific symptoms into account, particularly among low-income, community-dwelling older adults. OBJECTIVE: To evaluate program feasibility and MH outcomes among community-dwelling older adults randomized to 1 of 2 treatment arms of varying intensity of evidence based, collaborative MH care management services (ie, the Supporting Seniors Receiving Treatment and Intervention [SUSTAIN] program) that provide standardized, measurement-based, software-aided MH assessment and symptom monitoring and connection to community resources via telephone. DESIGN, SETTING, AND PARTICIPANTS: Trial participants were 1018 older, community-dwelling, low income adults prescribed an antidepressant or anxiolytic by a primary care or non MH professional and experiencing clinically significant MH symptoms at intake. The participant subsample was drawn from a larger parent sample of older adults enrolled in the SUSTAIN program. Individuals were randomized to receive MH symptom monitoring alone (hereafter monitoring alone) or MH symptom monitoring plus care management (hereafter care management) provided by an MH professional. Baseline characteristics were examined, and changes in clinical MH outcomes were evaluated at 3-month and 6-month follow-up. The study dates were August 5, 2010, to May 5, 2014. INTERVENTIONS: Monitoring alone or care management delivered by an MH professional. MAIN OUTCOMES AND MEASURES: Overall MH functioning (primary) and depressive and anxiety symptoms. RESULTS: A total of 509 participants were randomized to the monitoring alone group and 509 to the care management group; 377 and 401 completed >=2 research assessments in the monitoring alone and case management groups, respectively. Compared with those randomized to monitoring alone, individuals randomized to care management showed greater improvements in the 3 domains of MH functioning (beta [SE], 0.36 [0.12]; 95% CI, 0.12 to 0.60; P = .004), depressive symptoms (beta [SE], -0.20 [0.06]; 95% CI, -0.32 to -0.09; P < .001), and anxiety symptoms (beta [SE], -0.23 [0.05]; 95% CI, -0.33 to -0.14; P < .001) over time. CONCLUSIONS AND RELEVANCE: The SUSTAIN program, which provides assessment, monitoring, care management, and brief therapies for MH symptoms and needs in primary care settings, is feasible and scalable. A more intense level of care (ie, symptom monitoring plus care management) is associated with more favorable individual outcomes for low-income, community-dwelling older adults experiencing clinically significant MH symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02440594. PMID- 26558531 TI - Can silicon carbide serve as a saturable absorber for passive mode-locked fiber lasers? AB - The study presents a novel demonstration of a passively mode-locked erbium-doped fiber laser (EDFL) that is based on a silicon carbide (SixC1-x) saturable absorber. When the C/Si composition ratio is increased to 1.83, the SixC1-x film transforms from two-photon absorption to nonlinear saturable absorption, and the corresponding value reaches -3.9 * 10(-6) cm/W. The Si-rich SixC1-x film cannot mode lock the EDFL because it induced high intracavity loss through two-photon absorption. Even when a stoichiometric SiC is used, the EDFL is mode locked, similar to an EDFL operating under weak nonlinear-polarization-rotation condition. A C-rich SixC1-x film containing sp(2)-orbital C-C bonds with a linear absorbance of 0.172 and nonlinear absorbance of 0.04 at a 181 MW/cm(2) saturation intensity demonstrates nonlinear transmittance. The C-rich SixC1-x saturable absorber successfully generates a short mode-locked EDFL pulse of 470 fs. The fluctuation of the pulse-train envelope dropps considerably from 11.6% to 0.8% when a strong saturable-absorption-induced self-amplitude modulation process occurs in the C-rich SixC1-x film. PMID- 26558532 TI - Preoperative Chemoradiation in an Era of Suboptimal Clinical Staging. PMID- 26558533 TI - Moment expansion of the linear density-density response function. AB - We present a low rank moment expansion of the linear density-density response function. The general interacting (fully nonlocal) density-density response function is calculated by means of its spectral decomposition via an iterative Lanczos diagonalization technique within linear density functional perturbation theory. We derive a unitary transformation in the space of the eigenfunctions yielding subspaces with well-defined moments. This transformation generates the irreducible representations of the density-density response function with respect to rotations within SO(3). This allows to separate the contributions to the electronic response density from different multipole moments of the perturbation. Our representation maximally condenses the physically relevant information of the density-density response function required for intermolecular interactions, yielding a considerable reduction in dimensionality. We illustrate the performance and accuracy of our scheme by computing the electronic response density of a water molecule to a complex interaction potential. (c) 2015 Wiley Periodicals, Inc. PMID- 26558534 TI - Retracted: Ebola virus: an introduction and its pathology. AB - The Ebola viruses are causative agent of a severe Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) in human and other primates. Transmission of EVD occurs through the contact of body fluids from infected persons or animals, making it one of the most epidemic diseases worldwide. Underestimating the Ebola virus has cost loss of precious human lives in recent years. Ebola virus outbreak in year 2014 created a history, affecting a larger population in a wide geographical region of African sub-continent. EVD outbreaks have a case fatality rate of up to 70%. Ebola viruses are endemic in regions of Africa. Ebola viruses mainly target the hepatocytes, endothelial, and macrophage-rich lymphoid tissues and are characterized by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems. This impairment leads to multifocal necrosis and multi organ failure, and thus, in some ways, resembling septic shock. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. This review is focused on general characteristic of Ebola viruses, its pathogenesis, immunological response of host, and recent approaches for vaccine development against EVD. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26558535 TI - A large scale prediction of bacteriocin gene blocks suggests a wide functional spectrum for bacteriocins. AB - BACKGROUND: Bacteriocins are peptide-derived molecules produced by bacteria, whose recently-discovered functions include virulence factors and signaling molecules as well as their better known roles as antibiotics. To date, close to five hundred bacteriocins have been identified and classified. Recent discoveries have shown that bacteriocins are highly diverse and widely distributed among bacterial species. Given the heterogeneity of bacteriocin compounds, many tools struggle with identifying novel bacteriocins due to their vast sequence and structural diversity. Many bacteriocins undergo post-translational processing or modifications necessary for the biosynthesis of the final mature form. Enzymatic modification of bacteriocins as well as their export is achieved by proteins whose genes are often located in a discrete gene cluster proximal to the bacteriocin precursor gene, referred to as context genes in this study. Although bacteriocins themselves are structurally diverse, context genes have been shown to be largely conserved across unrelated species. METHODS: Using this knowledge, we set out to identify new candidates for context genes which may clarify how bacteriocins are synthesized, and identify new candidates for bacteriocins that bear no sequence similarity to known toxins. To achieve these goals, we have developed a software tool, Bacteriocin Operon and gene block Associator (BOA) that can identify homologous bacteriocin associated gene blocks and predict novel ones. BOA generates profile Hidden Markov Models from the clusters of bacteriocin context genes, and uses them to identify novel bacteriocin gene blocks and operons. RESULTS AND CONCLUSIONS: We provide a novel dataset of predicted bacteriocins and context genes. We also discover that several phyla have a strong preference for bacteriocin genes, suggesting distinct functions for this group of molecules. SOFTWARE AVAILABILITY: https://github.com/idoerg/BOA. PMID- 26558536 TI - mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets. AB - IL-17 mediates immune responses against extracellular pathogens, and it is associated with the development and pathogenesis of various autoimmune diseases. The expression of IL-17 is regulated by various intracellular signaling cascades. Recently, it has been shown that mechanistic target of rapamycin (mTOR) signaling, comprised mainly of mTORC1 signaling, plays a critical role in IL-17 expression. Here, we review the current knowledge regarding mechanisms by which mTORC1 regulates IL-17 expression. mTORC1 positively modulates IL-17 expression through several pathways, i.e. STAT3, -HIF-1alpha, -S6K1, and -S6K2. Amino acids (AAs) also regulate IL-17 expression by being the energy source for Th17 cells, and by activating mTORC1 signaling. Altogether, the AA-mTORC1-IL-17 axis has broad therapeutic implications for IL-17-associated diseases, such as EAE, allergies, and colitis. PMID- 26558537 TI - PANSS-6: a brief rating scale for the measurement of severity in schizophrenia. AB - OBJECTIVE: The 30-item Positive and Negative Syndrome Scale (PANSS-30) is the most widely used rating scale in schizophrenia, but too long for clinical use. Shorter PANSS versions have been proposed, including the PANSS-14 and PANSS-8. However, none of these PANSS versions has been validated using the parametric Rasch rating scale model, which evaluates 'scalability'. Scalability means that each item in a rating scale provides unique information regarding syndrome severity and is a statistical prerequisite for using the total score as a measure of overall severity. METHOD: Based on data from two randomized placebo-controlled trials in schizophrenia, we tested the scalability of PANSS-30, PANSS-14 and PANSS-8 by means of the parametric Rasch rating scale model. Furthermore, we tested whether a scalable PANSS version could separate efficacy of haloperidol and sertindole from placebo. RESULTS: Neither PANSS-30, PANSS-14 nor PANSS-8 was scalable. However, PANSS-6, consisting of the items: P1-Delusions, P2-Conceptual disorganization, P3-Hallucinations, N1-Blunted Affect, N4-Social withdrawal, N6 Lack of spontaneity and flow of conversation, was scalable. Furthermore, PANSS-6 captured superior symptom reduction and higher remission rates during treatment with haloperidol and sertindole vs. placebo. CONCLUSION: PANSS-6 is a short schizophrenia severity rating scale that adequately separates antipsychotic efficacy from that of placebo. PMID- 26558539 TI - Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. AB - OBJECTIVE: Case reports and hospital-based case-control studies suggest that cannabis use may increase the risk of stroke. We examined the risk of non-fatal stroke or transient ischemic attack (TIA) among cannabis users in the general community. METHOD: A general population survey of Australians aged 20-24 years (n=2,383), 40-44 years (n=2,525) and 60-64 years (n=2,547) was used to determine the odds of lifetime stroke or TIA among participants who had smoked cannabis in the past year while adjusting for other stroke risk factors. RESULTS: There were 153 stroke/TIA cases (2.1%). After adjusting for age cohort, past year cannabis users (n=1,043) had 3.3 times the rate of stroke/TIA (95% CI 1.8-6.3, p<0.001). The incidence rate ratio (IRR) reduced to 2.3 after adjustment for covariates related to stroke, including tobacco smoking (95% CI 1.1-4.5). Elevated stroke/TIA was specific to participants who used cannabis weekly or more often (IRR 4.7, 95% CI 2.1-10.7) with no elevation among participants who used cannabis less often. CONCLUSIONS: Heavy cannabis users in the general community have a higher rate of non-fatal stroke or transient ischemic attack than non-cannabis users. PMID- 26558538 TI - Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component. AB - AIMS: The aim of this non-systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis (OA) pain and how this pain mechanism can be addressed in terms of clinical diagnosis, investigation and treatment. METHODS: The authors undertook a non systematic review of the literature including a MEDLINE search (search terms included central sensitisation, osteoarthritis, osteoarthrosis) for relevant and current clinical studies, systematic reviews and narrative reviews. Case reports, letters to the editor and similar literature sources were excluded. Information was organised to allow a pragmatic approach to the discussion of the evidence and generation of practical recommendations. RESULTS: There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients. Clinically, a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non-pain features seen in other conditions involving central sensitisation. However, there are currently no diagnostic inventories for central sensitisation specific to OA. Biomarkers may be helpful for confirming the presence of central sensitisation, especially when there is diagnostic uncertainty. Several non-pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features. Multimodal therapy may be required to achieve control of symptoms. DISCUSSION: Clinicians should be aware of central sensitisation in patients with chronic OA pain, especially in patients presenting with severe pain with unusual features. PMID- 26558540 TI - BALB/c-congenic ANP32B-deficient mice reveal a modifying locus that determines viability. AB - We previously found that deletion of the multifunctional factor ANP32B (a.k.a. SSP29, APRIL, PAL31, PHAPI2) resulted in a severe but strain-specific defect resulting in perinatal lethality. The difficulty in generating an adult cohort of ANP32B-deficient animals limited our ability to examine adult phenotypes, particularly cancer-related phenotypes. We bred the Anp32b-null allele into the BALB/c and FVB/N genetic background. The BALB/c, but not the FVB/N, background provided sufficient frequency of adult Anp32b-null (Anp32b(-/-)) animals. From these, we found no apparent oncogenic role for this protein in mammary tumorigenesis contrary to what was predicted based on human data. We also found runtism, pathologies in various organ systems, and an unusual clinical chemistry signature in the adult Anp32b(-/-) mice. Intriguingly, genome-wide single nucleotide polymorphism analysis suggested that our colony retained an unlinked C57BL/6J locus at high frequency. Breeding this locus to homozygosity demonstrated that it had a strong effect on Anp32b(-/-) viability indicating that this locus contains a modifier gene of Anp32b with respect to development. This suggests a functionally important genetic interaction with one of a limited number of candidate genes, foremost among them being the variant histone gene H2afv. Using congenic breeding strategies, we have generated a viable ANP32B deficient animal in a mostly pure background. We have used this animal to reliably exclude mouse ANP32B as an important oncogene in mammary tumorigenesis. Our further phenotyping strengthens the evidence that ANP32B is a widespread regulator of gene expression. These studies may also impact the choice of subsequent groups with respect to congenic breeding versus de novo zygote targeting strategies for background analyses in mouse genetics. PMID- 26558541 TI - Early HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b). AB - BACKGROUND: We analyzed the early kinetics with integrase inhibitor treatment to gain new insights into viral dynamics. METHODOLOGY: We analyzed data from 39 HIV 1 infected, treatment-naive, participants: 28 treated with raltegravir (RAL; multiple doses) monotherapy for 9 days, and 11 with RAL 400 mg twice daily and emtricitabine (200 mg daily)/tenofovir disoproxil fumarate (300 mg daily). Plasma HIV-1 RNA was measured frequently; the data was fitted using a mathematical model of viral dynamics distinguishing between infected cells with unintegrated HIV DNA and productively infected cells. Parameters were estimated using mixed-effect models. RESULTS: RAL treatment led to a biphasic viral decline with a rapid first phase (1a) lasting approximately 5 days followed by a slower phase (1b). Phase 1a is attributed to the rapid elimination of productively infected cells. Phase 1b reflects the loss of infected cells with nonintegrated provirus due to cell loss and integration of HIV DNA. The half-lives of productively infected cells and of infected cells that had completed reverse transcription but had not yet integrated HIV DNA were approximately 19 h and between 3.6 and 5.8 days, respectively. The effectiveness of RAL in preventing proviral integration was 94% and 99.7%, for the combination therapy and monotherapy groups, respectively. CONCLUSION: We found that the first phase of viral decay with RAL therapy was composed of two subphases corresponding to the half-lives of infected cells with integrated proviruses and with unintegrated HIV-DNA. PMID- 26558542 TI - Incidence and progression of coronary artery calcium in HIV-infected and HIV uninfected men. AB - OBJECTIVE: The aim of this article is to determine whether HIV-infected (HIV+) men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected (HIV-) controls. DESIGN: Prospective observational study. SETTING: Multicenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University. PARTICIPANTS: Eight hundred and twenty-five men (541 HIV+ and 284 HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2-8 years). MAIN OUTCOME MEASURES: Incidence and progression of CAC assessed by cardiac CT. RESULTS: During follow-up, 21% of HIV+ men developed incident CAC compared with 16% of HIV- men. This association persisted after adjustment for traditional and HIV-associated risk factors: hazard ratio 1.64 (1.13-3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy. CONCLUSION: In this large study of HIV+ and HIV- men who underwent serial cardiac CT scan imaging, HIV+ men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13-3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV+ men. PMID- 26558543 TI - CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time. AB - BACKGROUND: CD4 cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4 cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4 decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. METHODS: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4 cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4 cell counts and an observation model relating actual CD4 measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4 cell counts through categories CD4 above 500, 350-500, 200-350 and 200 cells/MUl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. RESULTS: Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4 cell count above 500 cells/MUl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4 cell count less than 200 cells/MUl compared with 15.76 years for SPVL less than 4 log10 copies/ml. CONCLUSION: Many individuals already have CD4 cell count below 500 cells/MUl after seroconversion. SPVL strongly influences the rate of CD4 decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification. PMID- 26558544 TI - Once vs. twice-daily lopinavir/ritonavir in HIV-1-infected children. AB - OBJECTIVE: To evaluate whether once daily (q.d.) lopinavir/ritonavir is noninferior to twice daily (b.i.d.) dosing in children. DESIGN: International, multicentre, phase II/III, randomized, open-label, noninferiority trial (KONCERT/PENTA18/ANRS150). SETTING: Clinical centres participating in the PENTA, HIV-NAT and PHPT networks. PARTICIPANTS: Children/adolescents with HIV-1 RNA viral load less than 50 copies/ml for at least 24 weeks on lopinavir/ritonavir containing antiretroviral therapy. INTERVENTION: Children were randomized to continue lopinavir/ritonavir b.i.d. or change to q.d. MAIN OUTCOME MEASURE: Confirmed viral load >=50 copies/ml by 48 weeks (12% noninferiority margin). RESULTS: One hundred seventy-three children were randomized in the KONCERT trial (86 q.d., 87 b.i.d.); 46% men, median (IQR) age 11 (9-14) years, CD4% 33 (27 38)%. By week 48, 97 and 98% of time was spent on q.d. and b.i.d., respectively (one q.d. child lost at week 4). Twelve q.d. vs. seven b.i.d. children had confirmed viral load >=50 copies/ml within 48 weeks; estimated difference in percentage with viral load rebound 6% [90% CI (-2, 14)]. Numbers of children with grade 3/4 adverse events (11 vs. 7) or major resistance mutations (3 vs. 2) were similar, q.d. vs. b.i.d. (both P > 0.3). Among 26 children in an intrasubject lopinavir/ritonavir pharmacokinetic substudy, lower daily exposure (AUC0-24 161 h.mg/l vs. 224 h.mg/l) and lower Clast (1.03 mg/l vs. 5.69 mg/l) were observed with q.d. vs. b.i.d. dosing. CONCLUSION: Noninferiority for viral load suppression on q.d. vs. b.i.d. lopinavir/ritonavir was not demonstrated. Although results, therefore, do not support routine use of q.d. lopinavir/ritonavir, lack of safety concerns or resistance suggest that q.d. dosing remains an option in selected, adherent children, with close viral load monitoring. PMID- 26558545 TI - Field accuracy of fourth-generation rapid diagnostic tests for acute HIV-1: a systematic review. AB - INTRODUCTION: Fourth-generation HIV-1 rapid diagnostic tests (RDTs) detect HIV-1 p24 antigen to screen for acute HIV-1. However, diagnostic accuracy during clinical use may be suboptimal. METHODS: Clinical sensitivity and specificity of fourth-generation RDTs for acute HIV-1 were collated from field evaluation studies in adults identified by a systematic literature search. RESULTS: Four studies with 17 381 participants from Australia, Swaziland, the United Kingdom and Malawi were identified. All reported 0% sensitivity of the HIV-1 p24 component for acute HIV-1 diagnosis; 26 acute infections were missed. Specificity ranged from 98.3 to 99.9%. CONCLUSION: Fourth-generation RDTs are currently unsuitable for the detection of acute HIV-1. PMID- 26558548 TI - HIV treatment cascades: how can all countries reach the UNAIDS 90-90-90 target? PMID- 26558546 TI - Socioeconomic marginalization and plasma HIV-1 RNA nondetectability among individuals who use illicit drugs in a Canadian setting. AB - OBJECTIVE: Given that people who use illicit drugs (PWUD) often engage in prohibited income generation to support their basic needs, we sought to examine the role of these activities in shaping antiretroviral therapy (ART) adherence and plasma HIV RNA-1 viral load suppression among HIV-infected PWUD. DESIGN: Longitudinal analyses among HIV-positive, ART-exposed PWUD in the AIDS Care Cohort to evaluate Exposure to Survival Services prospective cohort study (2005 2013). METHODS: Generalized linear mixed-effects and mediation analyses examined the relationship between prohibited income generation (e.g., sex work, drug dealing, theft, street-based income) and virologic suppression (plasma viral load <=50 copies/ml plasma) adjusting for adherence and potential confounders. RESULTS: Among 687 HIV-infected PWUD, 391 (56.9%) individuals reported prohibited income generation activity during the study period. In multivariate analyses, prohibited income generation remained independently and negatively associated with virologic suppression (adjusted odds ratio: 0.68, 95% confidence interval: 0.52-0.88) following adjustment for hypothesized confounders, including high intensity drug use, ART adherence and homelessness. Although partially mediated by ART adherence, the relationship between prohibited income generation and virologic suppression was maintained in mediation analyses (Sobel statistic = 1.95, P = 0.05). CONCLUSION: Involvement in prohibited income generation decreases the likelihood of virologic suppression directly and indirectly through its negative association with ART adherence. These findings suggest that linkages between socioeconomic marginalization, the criminalization of illicit drug use, and insufficient employment opportunities may produce barriers to access and retention in care. Programmatic and policy interventions that decrease socioeconomic vulnerability may therefore reduce HIV-related morbidity, mortality, and onward transmission. PMID- 26558549 TI - Alarming rates of virological failure and drug resistance in patients on long term antiretroviral treatment in routine HIV clinics in Togo. AB - Information on efficacy of long-term antiretroviral treatment (ART) exposure in resource-limited countries is still scarce. In 767 patients attending routine HIV centers in Togo and receiving first-line ART for more than four years, 42% had viral load greater than 1000 copies/ml and either were on a completely ineffective ART regime or were with only a single drug active. The actual conditions to ensure lifelong ART in resource-limited countries can have dramatic long-term outcomes. PMID- 26558547 TI - Molecular analysis allows inference into HIV transmission among young men who have sex with men in the United States. AB - OBJECTIVE: The objective of this study is to understand the spread of HIV among and between age and racial/ethnic groups of men who engage in male-to-male sexual contact (MSM) in the United States. DESIGN: An analysis of HIV-1 pol sequences for MSM collected through the US National HIV Surveillance System (NHSS) during 2001-2012. METHODS: Pairwise genetic distance was calculated to determine potential transmission partners (those with very closely related nucleotide sequences, i.e. distance <=1.5%). We described race/ethnicity and age of potential transmission partners of MSM. RESULTS: Of 23 048 MSM with HIV sequences submitted to NHSS during 2000-2012, we identified potential transmission partners for 8880 (39%). Most potential transmission partners were of the same race/ethnicity (78% for blacks/African-Americans, 64% for whites and 49% for Hispanics/Latinos). This assortative mixing was even more pronounced in the youngest age groups. Significantly fewer young black/African-American and Hispanic/Latino MSM had older potential transmission partners than young white MSM. CONCLUSION: Black/African-American MSM, who are more profoundly affected by HIV, were more likely to have potential HIV transmission partners who were of the same race/ethnicity and similar in age, suggesting that disparities in HIV infections are in large part not due to age-disassortative relationships. Concerted efforts to increase access to preexposure prophylaxis, quality HIV care and effective treatment are needed to interrupt transmission chains among young, black/African-American MSM. PMID- 26558550 TI - Renal dysfunction and schistosomiasis among HIV-infected patients starting antiretroviral therapy in Mwanza, Tanzania. PMID- 26558551 TI - Gene regulation during development in the light of topologically associating domains. AB - During embryonic development, complex transcriptional programs govern the precision of gene expression. Many key developmental genes are regulated via cis regulatory elements that are located far away in the linear genome. How sequences located hundreds of kilobases away from a promoter can influence its activity has been the subject of numerous speculations, which all underline the importance of the 3D-organization of the genome. The recent advent of chromosome conformation capture techniques has put into focus the subdivision of the genome into topologically associating domains (TADs). TADs may influence regulatory activities on multiple levels. The relative invariance of TAD limits across cell types suggests that they may form fixed structural domains that could facilitate and/or confine long-range regulatory interactions. However, most recent studies suggest that interactions within TADs are more variable and dynamic than initially described. Hence, different models are emerging regarding how TADs shape the complex 3D conformations, and thereafter influence the networks of cis interactions that govern gene expression during development. For further resources related to this article, please visit the WIREs website. PMID- 26558552 TI - Highly Selective Addition of a Broad Spectrum of Trimethylsilane Pro-nucleophiles to N-tert-Butanesulfinyl Imines. AB - Addition of organotrimethylsilane reagents to chiral N-tert-butanesulfinyl imines can be achieved in good yields and with excellent diastereoselectivities by employing TMSO(-)/Bu4N(+) as a Lewis base activator in THF. A variety of aliphatic, aromatic, heteroaromatic and organometallic chiral imines were utilised as electrophiles for the synthesis of enantioenriched N-tert butanesulfinyl amides. Remarkably, the same sets of reaction conditions could be used with a highly diverse range of bench-stable organotrimethylsilane reagents, which highlights the generality and robustness of this methodology. PMID- 26558553 TI - The Royal North Shore Hospital Emergency Department airway registry: Closing the audit loop. AB - OBJECTIVE: We aim to investigate whether a bundle of changes made to the practice of endotracheal intubation in our ED was associated with an improvement in first pass success rate and a reduction in the incidence of complications. METHODS: We used a prospective observational study. RESULTS: The data on 360 patients who were intubated during an 18-month period following the introduction of these changes were compared with our previously published observational data. Success on first attempt at intubation improved 83.4% to 93.9% (P < 0.0001). The proportion of patients with one or more complication fell from 29.0% to 19.4% (P < 0.042). Oesophageal intubation fell from 4.0% to 0.3% (P < 0.001), and there was a non-significant reduction in the rate of desaturation, from 15.6% to 10.9% (P < 0.07). CONCLUSION: We have shown that, through the introduction of a bundle of changes that spans the domains of staff training, equipment and practice standardisation, we have made significant improvements in the safety of patients undergoing endotracheal intubation in our ED. PMID- 26558555 TI - Line edge roughness of a latent image in post-optical lithography. AB - The progress of electronic devices has been supported by advances in 'top-down' nanotechnology, namely lithography, which reached a scale of 90 nm on the mass production stage in 2005. The energy of the exposure source would exceed the ionization potential of the resist materials at the 32 nm scale with the deployment of extreme ultraviolet (EUV) light or an electron beam (EB). Among the issues of nanoscale fabrication with chemically amplified (CA) resists, line edge roughness (LER) is the most serious concern. Here, we report a Monte Carlo simulation of a latent image LER caused by ionization, in terms of proton dynamics, acid diffusion, and the effect of amine additives. The minimum LER (defined as three times the standard deviation) after post-exposure baking was ~9.5 nm for a 5 uC cm(-2) exposure dose with 0.5 wt% amine. Although the deployment of a high-energy exposure source is the only method that allows further miniaturization after ArF immersion lithography, the acid generation mechanism, clarified for the first time in this paper, will emerge as a critical factor in limiting the availability of post-optical lithography. PMID- 26558554 TI - Predictive factors for recurrence of cryptoglandular fistulae characterized by preoperative three-dimensional endoanal ultrasound. AB - AIM: Precise information regarding the location of an anal fistula and its relationship to adjacent structures is necessary for selecting the best surgical strategy. Retrospective and cross-sectional studies were performed to determine predictive factors for recurrence of anal fistula from preoperative examination by three-dimensional endoanal ultrasound (3D-EAUS). METHOD: Patients in our tertiary centre and in a private centre specialized in proctology undergoing preoperative 3D-EAUS for cryptoglandular anal fistulae between 2002 and 2012 were included. A questionnaire was sent in September 2013 to assess the patient's condition with regard to recurrence. Variables checked for association with recurrence were gender, type of centre, previous fistula surgery, secondary track formation and classification of the fistula. RESULTS: There were 143 patients of whom 96 had a low fistula treated by fistulotomy, 28 a high fistula treated by fistulectomy and 19 a high fistula treated by fistulectomy combined with a mucosal advancement flap. The median duration of follow-up was 26 (2-118) months. The fistula recurred in 40 (27%) patients. Independent risk factors included the presence of secondary track formation [hazard ratio 2.4 (95% CI 1.2-51), P = 0.016] and previous fistula surgery [hazard ratio 1.2 (95% CI 1.0-4.6), P = 0.041]. Agreement between the 3D-EAUS examination and the evaluation under anaesthesia regarding the site of the internal opening, classification of the fistula and the presence of secondary tracks was 97%, 98% and 78%. CONCLUSION: The identification of secondary tracks by preoperative 3D-EAUS examination was the strongest independent risk factor for recurrence. This stresses the importance of preoperative 3D-EAUS in mapping the pathological anatomy of the fistula and a thorough search for secondary track formation during surgery. PMID- 26558556 TI - Aperture scanning near-field optical microscopy and spectroscopy of single terrylene molecules at 1.8 K. AB - Single-molecule imaging and spectroscopy using an aperture scanning near-field optical microscope operating at 1.8 K in a helium bath cryostat is demonstrated. From near-field images at constant excitation frequency, the orientation of single molecules can be deduced. Spectral information is obtained using both near field and confocal excitation schemes by scanning the excitation frequency at a fixed sample position. Differences between near-field and confocal spectra are discussed in terms of the position with respect to the aperture and the molecular orientation. PMID- 26558557 TI - Effective amino-functionalization of carbon nanotubes for reinforcing epoxy polymer composites. AB - An effective functionalization method was investigated to take full advantage of the exceptional performance of both carbon nanotubes and epoxy polymer for composite application. Epoxy polymer curing agent, EPI-W, was grafted to the single-walled carbon nanotubes through diazotization. Fourier transformed infrared spectroscopy, Raman spectroscopy, differential scanning calorimetry, dynamical mechanical analysis and thermo-gravimetric analysis were performed to characterize the functionalization effect. The degree of functionalization was estimated to be 1 in 50 carbons in the nanotube framework. The elastic modulus of the nanocomposite was enhanced 24.6% with only 0.5 wt% loading of functionalized carbon nanotubes, in contrast to the 3.2% increase of un-functionalized carbon nanotube reinforced composite. This significant improvement suggested an effective way to realize an industrial application of nanotubes reinforcing epoxy composite. PMID- 26558558 TI - Electrospun polymer nanofibres with small diameters. AB - Nylon-4,6 nanofibres with diameters ranging from about 1 um down to 1 nm were prepared by electrospinning. The fibre diameter was varied by adjusting the concentration of the polymer solution. Electrospinning of a concentrated solution of as high as 20% nylon-4,6 by weight in formic acid produced a ribbon-like electrospun fibre with a ribbon width of about 850 nm. A semi-dilute concentration of 2% nylon-4,6 by weight produced the thinnest nylon-4,6 nanofibres with diameters of 1.6 nm or less. A small amount of pyridine was added to the electrospinning solution to avoid the formation of beaded nanofibres in the course of electrospinning at low concentrations. Scanning and transmission electron microscopy were used to characterize the size of the nanofibres. An ultra-thin nylon-4,6 nanofibre of 1.2 nm diameter might contain six or seven nylon-4,6 molecules in a typical cross-section of the fibre. PMID- 26558559 TI - Local measurement of secondary electron emission from ZnO-coated carbon nanotubes. AB - The secondary electron emission (SEE) of ZnO-coated carbon nanotubes (CNTs) was measured using a biasing technique in a scanning electron microscope. The SEE yield of the ZnO-coated CNTs is higher than that of the ZnO film deposited on Si substrates. Direct observation of the variation in SEE from tip-end and non-CNT positions was demonstrated. Local measurement reveals that the SEE yield at the tip-end of the ZnO-coated CNTs is much higher than that of non-CNT positions. The enhancement of SEE is attributed to the strong local field generated at the tip of the CNTs. PMID- 26558560 TI - Adsorption of PTCDA on a partially KBr covered Ag(111) substrate. AB - Ordered growth of 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) on Ag(111) partially covered by one or two monolayers of KBr was investigated by non contact AFM with molecular resolution. Different adsorption patterns are found on the pure substrate, the one covered by a single monolayer, and the one covered by two monolayers KBr. Simulations with an extended Ising-type model reproduce these experimental patterns very well. The adsorbate-adsorbate and the adsorbate substrate interaction parameters obtained from the simulation are discussed with respect to the interactions at the Ag(111)|KBr interface. As a result, alkali halide covered metals can be used for tuning the interactions and designing adsorption systems, which opens up new possibilities in the control of self assembled nanostructures. PMID- 26558561 TI - Atomic force microscopy with inherent disturbance suppression for nanostructure imaging. AB - Scanning probe imaging is often limited by disturbances, or mechanical noise, from the environment that couple into the microscope. We demonstrate, on a modified commercial atomic force microscope, that adding an interferometer as a secondary sensor to measure the separation between the base of the cantilever and the sample during conventional feedback scanning can result in real-time images with inherently suppressed out-of-plane disturbances. The modified microscope has the ability to resolve nanometre-scale features in situations where out-of-plane disturbances are comparable to, or even several orders of magnitude greater than, the scale of the topography. We present images of DNA in air from this microscope in tapping mode without vibration isolation, and show improved clarity using the interferometer as the imaging signal. The inherent disturbance suppression approach is applicable to all scanning probe imaging techniques. PMID- 26558562 TI - Crystal-structure-dependent photoluminescence from InP nanowires. AB - The formation and photoluminescence (PL) of InP nanowires grown by metal organic vapour phase epitaxy on InP(111)B substrates, using colloidal gold nanoparticles as catalysts, are investigated. The dependence of the orientation and dimensions of the nanowires on the growth temperature is studied using scanning electron microscopy. Vertically aligned [Formula: see text] oriented nanowires with a mean base diameter in the range 50-150 nm, and a tip diameter of 50 nm, show a PL blue shift of about 80 meV compared to the substrate. Blue-shift due to quantum confinement is ruled out because of the large diameter of the nanowires. A clear correlation between the orientation of the nanowires on the substrate and the PL peak position is observed. Based on x-ray diffraction and transmission electron microscopy measurements, it is proposed that the as-grown vertically oriented nanowires have crystallized in the wurtzite lattice instead of in the zinc-blende structure, which results in a blue-shifted PL. PMID- 26558563 TI - Formation and luminescence of nanoterraces and elongated structures in sintered TiO2. AB - Samples of rutile TiO2 have been prepared by sintering compacted powders under argon flow. Long (above 20 h) sintering times at 1500 degrees C led to the formation of rods with squared cross-sections in a broad range of sizes. A two step annealing treatment, at two temperatures, was found to favour the growth of low-dimensional elongated structures as well as a terraced structure on the grain surface, producing samples with high surface to volume ratio. The cathodoluminescence (CL) spectrum of the initial powder, shows an emission centred at about 2.40 eV, which can be separated into three Gaussian bands at 2.19, 2.30 and 2.55 eV. The main features of the CL spectra of sintered samples are an infrared band at 1.52 eV and a complex band in the visible range, whose peak position shifts with the annealing temperature. In samples sintered for 30 h an emission at 1.80 eV appears, while the dominant emission at 1.52 eV, due to titanium interstitials, is quenched. PMID- 26558564 TI - Solubilization, purification and functionalization of carbon nanotubes using polyoxometalate. AB - In this work, we developed a convenient and efficient method for solubilization, purification and functionalization of carbon nanotubes (CNTs) using a versatile reagent (phosphotungstic acid (HPW)). Because HPW can spontaneously attach to graphite walls as polyanions and provide static repulsion, CNT aggregates were divided into individual and small bundles of CNTs and turned into a stable solution by sonication in the presence of HPW. Amorphous carbon impurities and metal catalysts in the raw CNTs were removed by centrifugation and filtration. Finally, purified CNTs with a yield of 82 wt% were obtained. Using HPW on graphite walls as an electrostatic and acid anchor, positively charged titania nanoparticles and albumin molecules were successfully assembled around CNTs without altering their delocalized pi-electron system. The versatility of this simple approach could be extended beyond inorganic nanoparticles and proteins, to other systems with desired properties. PMID- 26558565 TI - Large-area fabrication of periodic Fe nanorings with controllable aspect ratios in porous alumina templates. AB - Highly uniform Fe nanoring arrays in porous anodic alumina templates are fabricated by physical vapour deposition and grazing ion milling techniques. The nanorings have aspect ratios ranging from 0.8 to 4, depending on the deposition conditions. The outer diameter of the individual nanorings, and the area density and distribution patterns are completely determined by the template used. Selected-area electron diffraction reveals that these nanorings have a polycrystalline microstructure. The nanoring fabrication method demonstrated here can be extended to other materials. PMID- 26558566 TI - Carboxyl-cored dendrimer and toluene-assisted fabrication of uniform platinum nanodendrites at a water/oil interface and their potential application as a catalyst. AB - Uniform platinum nanodendrites have been prepared at a water/oil interface by a facile catalyst-free method at room temperature. This is carried out by introducing NaBH4 into the platinum precursor solution in the presence of the second generation of carboxyl-cored dendrimer ([G-2]-CO2H dendrimer) and toluene to act as a protective agent and a linker, respectively. The average fractal dimension of 1.61 of the obtained platinum nanodendrites is calculated by analysing the transmission electron micrographs using the programs Fractal Dimension Version 1.1 and Fractal Dimension Calculator. Control experiments show that the fabrication of platinum nanodendrites can be operated with a wide parameter window, which undoubtedly raises the degree of control of the synthesis process. The potential application of such a nanostructure as a catalyst is investigated, and the results reveal that they show highly efficient catalytic properties for the typical redox reaction between hexacyanoferrate (III) and thiosulfate ions at 301 K. PMID- 26558567 TI - Investigation of micro-electro-mechanical processing characteristics of layered boron nitride and carbon films. AB - A microsquare fabrication process is developed for the investigation of the processing characteristics of boron nitride and carbon (C/BN)n and (BN/C)n films with a 4 nm nanoperiod multilayer structure. Simultaneous surface topography, friction and current measurements were performed on the multilayer films by conductive atomic force microscopy (AFM) with force modulation, which permits the quantitative recording of current and frictional force as functions of the applied force. The current image showed that highly conducting sites formed on carbon (C) layers and that nonconducting sites existed on boron nitride (BN) layers and/or mixed layers. Furthermore, amplitude response (friction force) images show that the conducting sites have a low frictional force, whereas the nonconducting sites have a high frictional force. This is thought to be due to the structure phase of the nanostructure of the films. Further, the result that the nonconducting sites have a high amplitude response (friction) implies the existence of a mixed layer (interface) between the C and BN layers. It is suggested that friction and surface-current measurements are effective methods of investigating multilayer nanostructural surfaces and fabricating micro-electro mechanical processing systems of a high precision. PMID- 26558568 TI - Dynamic behaviour in piezoresponse force microscopy. AB - Frequency-dependent dynamic behaviour in piezoresponse force microscopy (PFM) implemented on a beam-deflection atomic force microscope (AFM) is analysed using a combination of modelling and experimental measurements. The PFM signal is comprised of contributions from local electrostatic forces acting on the tip, distributed forces acting on the cantilever, and three components of the electromechanical response vector. These interactions result in the flexural and torsional oscillations of the cantilever, detected as vertical and lateral PFM signals. The relative magnitudes of these contributions depend on geometric parameters of the system, on the stiffnesses and frictional forces of the tip surface junction, and on the frequency of operation. The dynamic signal formation mechanism in PFM is analysed and conditions for optimal PFM imaging are formulated. An experimental approach for probing cantilever dynamics using frequency-bias spectroscopy and deconvolution of electromechanical and electrostatic contrast is implemented. PMID- 26558569 TI - Magnetic antidot nanostructures: effect of lattice geometry. AB - We investigate the effect of lattice geometry on the magnetic anisotropy and transport properties of Ni80Fe20 antidot nanostructures. The structures were fabricated using deep ultra-violet lithography at 248 nm exposure wavelength. For an antidot array with a square lattice, a fourfold magnetic anisotropy with alternating hard axis and easy axis every 45 degrees was observed. The honeycomb and rhomboid antidot lattice, however, both show a sixfold anisotropy, conforming well to the symmetry of their respective lattices. The magnetic hysteresis and micromagnetic simulation of the spin states at remanence show that the magnetization reversal process is very sensitive to the lattice arrangement of the holes. From the magnetotransport measurements, both the current density distribution and the magnetoresistance behaviour are markedly dependent on the antidot lattice geometry, in agreement with our transport simulations. PMID- 26558570 TI - Theoretical investigation on the stability and properties of a (10,0) BN-AlN nanotube junction. AB - The energetic, electronic and structural properties of a heterojunction formed by BN and AlN (10,0) nanotubes have been studied using first principles density functional theory. The differences between the AlN and BN nanotubes lead to structural rearrangements mainly at the junction layers. Two different types of junction occur, and net charges of opposite signs appear in each of them, with a resulting electric dipole along the heterojunction axis. The calculated band offset shows a staggered band line-up, with the heterojunction forming a one dimensional array of quantum dots. PMID- 26558571 TI - Visible quantum cutting in GdF3:Eu(3+) nanocrystals via downconversion. AB - GdF3:Eu(3+) nanocrystals (NCs) and nanorods were synthesized by a microemulsion mediated hydrothermal process. The structure, shape and particle size were characterized by means of x-ray diffraction (XRD) and transmission electron microscopy (TEM). The vacuum ultraviolet (VUV) spectrum of GdF3:Eu(3+) NCs shows that the Gd(3+) ion can absorb one VUV photon excited in the (6)GJ levels and relaxes through two-step energy transfer to Eu(3+), yielding two visible photons at room temperature. The visible quantum efficiency of GdF3:Eu(3+) NCs was calculated to be close to 170% by the peak intensity ratio of correlative transition emission under VUV excitation at 160 nm. PMID- 26558572 TI - Formation of mid-infrared emissive InAs quantum dots on a graded InxGa1-xAs/InP matrix with a more uniform size and higher density under safer growth conditions. AB - InAs mid-infrared emissive quantum dots (QDs) grown on a graded InxGa1-xAs/InP matrix with more uniform size and higher dot density have been successfully prepared by low pressure metal organic chemical vapour deposition (LP-MOCVD) under safer growth conditions. Low toxic tertiarybutylarsine and tertiarybutylphosphine sources were used to replace the high toxic arsine and phosphine in the MOCVD growth. To improve the process safety further, inertial N2 instead of the normally used explosive H2 was used as the carrier gas. Initially, by using a two-step growth method, uniform InAs QDs with a high dot density of 1.3 * 10(10) cm(-2) have been successfully grown on a InGaAs/InP matrix. The emission wavelength of the QDs reaches >2.1 um. The low temperature photoluminescence spectrum of the QDs grown by the two-step growth has much narrower linewidth and higher intensity than that of the QDs grown by using normal Stranski-Krastanow (S-K) and atomic layer epitaxy (ALE) growth methods. PMID- 26558573 TI - Fabrication and magnetotransport properties of ordered sub-100 nm pseudo-spin valve element arrays. AB - We prepared ordered sub-100 nm pseudo-spin-valve (PSV) element arrays by electrodeposition of NiFe/Cu/Co into the pores of self-organized nanoporous anodized aluminium templates. Field-emission scanning electron microscopy reveals that the sub-100 nm PSV arrays, of uniform size, are well separated and exhibit a perfect two-dimensional array with a hexagonal pattern. The easy-axis hysteresis loops show two distinct steps related to the separate reversal of soft (NiFe) and hard (Co) layers. The switching fields of the PSV arrays are approximately -50 Oe for the NiFe and 570 Oe for the Co. The dependence of the magnetoresistance on the Cu spacer layer thickness indicates the presence of an oscillatory interlayer exchange coupling through the Cu layers. PMID- 26558574 TI - Model for the effective thermal conductivity of carbon nanotube composites. AB - We present a novel model of the effective thermal conductivity for carbon nanotube composites by incorporating the interface thermal resistance with an average polarization theory. The dependence of the effective thermal conductivity on nanotube length, diameter, concentration, and interface thermal resistance has been taken care of simultaneously in our treatment. The model predicts that the large length of the carbon nanotubes embedded plays a key role in the thermal conductivity enhancement, while the large interface thermal resistance across the nanotube-matrix interface causes a significant degradation. Interestingly, the model predicts that the nanotube diameter has a very small effect on the thermal conductivity enhancement of the nanotube composites. In addition, the model predicts that the thermal conductivity enhancement of nanotube composites increases rapidly with decreasing the thermal conductivity of the matrix and increases with increasing the thermal conductivity of the carbon nanotube. Predictions from the novel model are in excellent agreement with the experimentally observed values of the effective thermal conductivity of carbon nanotube nanofluids which the classical models have not been able to explain. PMID- 26558575 TI - Fabrication of polymeric hollow nanospheres, hollow nanocubes and hollow plates. AB - A facile strategy for fabricating polypyrrole-chitosan (PPy-CS) hollow nanostructures with different shapes (sphere, cube and plate) and a wide range of sizes (from 35 to 600 nm) is described. These hollow structures have been fabricated using silver bromide as a single template material for polymer nucleation and growth. PPy-CS hollow nanostructures are formed by reaction with an etching agent to remove the core. These hollow nanostructures have been extensively characterized using various techniques such as TEM, FT-IR, UV-vis, and XRD. PMID- 26558577 TI - Modelling of nanoparticle formation during spray pyrolysis. AB - A mathematical model for the evaporation of micro- and nano-sized solution droplets is developed. This model is used to predict whether the particles produced by spray drying and pyrolysis are fully filled or hollow. The model includes the non-continuum effects on the droplet evaporation. This is achieved by combining an interpolation formula based on the numerical solution of the Boltzmann equation for the transition regime with the continuum based governing equations. Results show that the non-continuum effects can be significant for the evaporation of submicron and nano-sized droplets in atmospheric pressures. Correlations for the final particle size and its wall thickness in terms of reactor temperature and pressure and the initial solution concentration are developed. The predictions are in good agreement with experiments performed on the submicron zirconia particles, prepared by spray pyrolysis. PMID- 26558576 TI - Large-scale production of carbon-coated copper nanoparticles for sensor applications. AB - Copper nanoparticles with a mean carbon coating of about 1 nm were continuously produced at up to 10 g h(-1) using a modified flame spray synthesis unit under highly reducing conditions. Raman spectroscopy and solid state (13)C magic angle spinning nuclear magnetic resonance spectroscopy revealed that the thin carbon layer consisted of a sp(2)-hybridized carbon modification in the form of graphene stacks. The carbon layer protected the copper nanoparticles from oxidation in air. Bulk pills of pressed carbon/copper nanoparticles displayed a highly pressure- and temperature-dependent electrical conductivity with sensitivity at least comparable to commercial materials. These properties suggest the use of thin carbon/copper nanocomposites as novel, low-cost sensor materials and offer a metal-based alternative to the currently used brittle oxidic spinels or perovskites. PMID- 26558578 TI - The degenerate Fermi gas of pi electrons in fullerenes and the sigma surface instabilities. AB - The departure from perfect spherical symmetry in the case of fullerenes (C60 being the sole exception) induces instabilities due to the stresses generated by the pentagonal protrusions in the sigma-bonded surfaces. By assuming sigma-pi separability and treating pi electrons as a degenerate Fermi gas in the two shells around the central sigma structure, the resulting degeneracy pressures can further enhance the sigma-surface initiated instabilities for non-icosahedral structures (especially for those C60) with large protrusions. Under certain circumstances the net degeneracy pressure across the sigma surface may have a structure stabilizing effect. The role of the pi-electron degeneracy in a broad range of fullerenes from C20 to C1500 and its effects on fullerene stability are investigated. PMID- 26558579 TI - Synthesis and low-temperature photoluminescence properties of SnO2 nanowires and nanobelts. AB - Ultra-long rutile tin dioxide nanowires and nanobelts are synthesized by thermal oxidation of tin powder using gold film as the catalyst. Nanowire or nanobelts can be selectively produced by tuning the reaction temperature. The vapour-liquid solid growth mechanism is proposed. The band gaps of the nanowires and nanobelts are 3.74 and 3.81 eV respectively, determined from UV/visible absorption spectral results. The SnO2 nanowires show stable photoluminescence with two emission peaks centred at around 470 and 560 nm. Their wavelengths stay almost fixed while their intensities depend sensitively on the temperatures within the examination ranges from 10 to 300 K. The SnO2 nanobelts show similar photoluminescence behaviours and the origin of the luminescence is discussed. PMID- 26558580 TI - A simple hydrothermal method for the growth of Bi2Se3 nanorods. AB - Bi2Se3 nanorods have been synthesized through a simple hydrothermal reduction approach. The nanorods formed were ~10 nm in diameter and 100-200 nm in length. XRD characterization suggested that the product consisted of the hexagonal phase of pure Bi2Se3. EDX and XPS studies further confirmed the composition and purity of the product. A possible mechanism for the reaction is proposed, where Bi2Se3 microsheets are presumed to be the intermediate for the formation of the nanorods. The effect of solvent on the morphology of the final product is discussed, where, in the presence of aprotic solvent DMF, nanoparticle formation is observed. A bandgap of 2.25 eV is observed from the UV-visible absorption spectra. PMID- 26558581 TI - Pulsed electrodeposition of single-crystalline Bi2Te3 nanowire arrays. AB - Thermoelectric material Bi2Te3 nanowire arrays have been successfully prepared by pulsed electrochemical deposition into the nanochannels of porous anodic alumina membranes. X-ray diffraction analyses show that the as-synthesized nanowires have a highly preferential orientation. Scanning electron microscopy, transmission electron microscopy, and high-resolution transmission electron microscopy observations indicate that the high-filling-rate and uniform Bi2Te3 nanowires are single crystalline. Energy dispersive spectrometer analyses indicate that the compositions of the nanowires can be controlled by changing the potentials and the solution concentrations. The electrical resistance measurements indicate that the resistances increase with decreasing temperature and show a typical semiconductor characteristic. The growth mechanism is discussed together with the electrochemical deposition process studies. PMID- 26558582 TI - InGaN self-assembled quantum dots grown by metal-organic chemical vapour deposition with growth interruption. AB - Self-assembled InGaN quantum dots (QDs) were grown by metal-organic chemical vapour deposition with growth interruption at low V/III ratio and low growth temperature on sapphire substrates. The effects of the interruption time on the morphological and optical properties of InGaN QDs were studied. The results show that the growth interruption can modify the dimension and distribution of InGaN QDs, and cause the QD emission wavelength to blue shift with increasing interruption time. A density of InGaN QDs of about 4.5 * 10(10) cm(-2) with an average lateral size of 11.5 nm and an average height of 1.6 nm can be obtained by using a growth interruption time of 60 s. PMID- 26558583 TI - Substrate and laser power dependence of surface-enhanced Raman scattering from a silver oxide film. AB - We report a method to improve the efficiency of surface-enhanced Raman scattering (SERS) from a silver oxide film. A 632.8 nm He-Ne laser beam was focused on silver oxide films deposited on different substrates (silica, TiO2, Si). We found that the substrate material greatly affected the SERS efficiency, and that silica substrate showed the highest efficiency among the materials measured. Scanning electron microscopy observations revealed that silver nanoparticles were generated within the focused laser spot. Computer simulations of the thermal profile based upon data from experimental observations were also carried out. It was found that the temperature of the silver oxide film differed greatly according to the substrate. We infer that substrates that allow higher silver oxide-film temperatures to be attained are more suitable for efficient SERS. PMID- 26558584 TI - A parametric study on the synthesis of carbon nanotubes through arc-discharge in water. AB - A parametric study was carried out on a novel carbon nanotube (CNT) synthesis using 'arc-discharge in solution' (ADS). The carbon nanostructure yield as a function of time, the rate of erosion of the anode, and the rate of deposition of carbonaceous materials on the cathode electrode were investigated. Amperage dependent normalized kinetic parameters were evaluated. The production rate of carbon nanostructures including CNTs at 75 A is as high as 5.89 +/- 0.28 g min( 1). Thermogravimetric analysis and x-ray diffraction studies reveal high purity of the carbon nanostructures collected from water and have a very good agreement with electron microscopy analyses. Very high surface area of the pristine multiwalled CNTs and nanostructures (84 +/- 3.5 m(2) g(-1)) was measured using BET. The dynamic light scattering (DLS) analysis shows further agreement with the amperage dependent studies. PMID- 26558585 TI - Synthesis of La and Nb doped PZT powder by the gel-combustion method. AB - Lanthanum and niobium doped PZT with composition (Pb0.93La0.07)[(Zr0.60Ti0.40)]0.9825Nb0.0175O3 (PZTLN) was prepared by the gel combustion method. A precursor sol was obtained from lead nitrate, zirconyl nitrate, lanthanum oxide, peroxo-citrato-niobium and a peroxo-citrate complex of titanium isopropoxide as starting precursors. Various molar ratios of citrate/nitrate (CA/NO3(-) = 1.3, 0.36 and 0.09) were used to prepare very fine powders of PZTLN. The gels resulting from these sols were transformed into powders by an auto-combustion process at <=400 degrees C. The powders consisted of rhombohedral PZT (PbZr0.60Ti0.40O3), pyrochlore (Pb2Ti2O6) and lead carbonate (Pb2O.CO3) phases. The pure rhombohedral phase is found in PZTLN pellets sintered at 1100 degrees C for all citrate/nitrate ratios. Titanium and niobium precursors were modified with peroxo radicals. During the gel-combustion reaction, the temperature of the gel increases, leading to lead evaporation. The loss of lead as well as the particle size increases as the CA/NO3(-) ratio decreases. The smallest grained powder (about 50 nm) was obtained with the ratio CA/NO3(-) equal to 0.09. PMID- 26558586 TI - Synthesis and I-V properties of aligned copper nanowires. AB - This paper reports the synthesis of well-aligned copper nanowires using an electrochemical deposition template technique. The electrical properties of copper nanowire arrays synthesized within vertical pores of alumina template were measured using a current-sensing atomic force microscope (AFM), with bias voltage applied between the AFM tip and the gold back-electrode. Nonlinear current voltage (I-V) characteristics of copper nanowire arrays are observed; this is attributed to the impurities near the wire-lead contact region. These vertical copper nanowire arrays are suitable for use in fabricating nanoelectronic devices. PMID- 26558587 TI - Growth mechanism of tubular ZnO formed in aqueous solution. AB - Tubular ZnO microstructural arrays were fabricated by a hydrothermal decomposition method. The dependence of the morphologies on the growth time and temperature was investigated in detail. An experiment was carried out to determine the mechanism of tubular ZnO formation. Our results showed that ZnO microtubes originated from an ageing process from ZnO microrods at a lower temperature (compared to the temperature when hydrothermal deposition of ZnO microrods was dominant) due to the preferential chemical dissolution of the metastable Zn-rich (0001) polar surfaces. A growth model was proposed based on the coexistence of hydrothermal deposition and dissolution of ZnO in the fabrication process. PMID- 26558588 TI - Luminescent properties and characterization of Gd2O3:Eu(3+)@SiO2 and Gd2Ti2O7:Eu(3+)@SiO2 core-shell phosphors prepared by a sol-gel process. AB - Gd2O3:Eu(3+) and Gd2Ti2O7:Eu(3+) films 10 nm in thickness were individually coated onto silica spheres (particle size of 150-170 nm) using the sol-gel method. The synthesized materials were addressed as Gd2O3:Eu(3+)@SiO2 and Gd2Ti2O7:Eu(3+)@SiO2 phosphors. An x-ray powder diffractometer (XRD), field emission scanning electron microscope (FE-SEM), high-resolution transmission electron microscope (HR-TEM), and photoluminescence spectrophotometer (PL) were employed to characterize the core-shell phosphors. Uniform core-shell phosphor particles were observed using FE-SEM. The XRD and HR-TEM results indicated that the coated-shell layer was well crystallized after sintering at 1000 degrees C. The Gd2O3:Eu(3+)@SiO2 PL measurement showed a red emission at the main 615 nm wavelength. The Gd2Ti2O7:Eu(3+)@SiO2 phosphor showed an orange-red emission at the 588 and 615 nm wavelengths. In comparison with the Gd2O3:Eu(3+) and Gd2Ti2O7:Eu(3+) bulk material results, the core-shell phosphors maintained the same emission ability as the bulk materials and the novel core-shell phosphors possessed great potential in quantum phosphor applications. PMID- 26558589 TI - Nonlinear I-V characteristics of nanocrystalline SnO2. AB - Current versus voltage characteristics (I-V) of nanocrystalline SnO2 materials have been investigated in air at room temperature. The samples were prepared by the inert gas condensation technique (IGCT) as well as by chemical methods. X-ray diffraction studies showed a tetragonal rutile structure for all the samples. Microstructural studies were performed with transmission electron microscopy. All the samples exhibited nonlinear I-V characteristics of the current-controlled negative resistance (CCNR) type. The results show that the threshold field (break down) voltage is higher for the samples prepared by the IGCT method than for those prepared by the chemical method due to the formation of a tin oxide layer over the crystalline tin. It is also found that the threshold field increases with the decrease in grain size. PMID- 26558590 TI - Critical issues in the focused ion beam patterning of nanometric hole matrixes on GaAs based semiconducting devices. AB - This work investigates the critical issues in the focused ion beam (FIB) nanopatterning of semiconducting devices. Matrixes of holes with diameter of about 150 nm were drilled by FIB on the topmost layers of a quantum dot based device. In order to study the presence of artefacts in the active region of the device, the milling parameters were investigated. A careful analysis of the ion beam effects on the structural and morphological features of the holes, mainly due to the heterogeneous composition of the layers to be milled, demonstrated that important deviations from the expected structures, in terms of size, shape and geometry of the holes, as well as layer amorphization and damage, occur. PMID- 26558591 TI - A general route for the rapid synthesis of one-dimensional nanostructured single crystal Te, Se and Se-Te alloys directly from Te or/and Se powders. AB - A general and template-free 'disproportionation and reversal' route was developed to synthesize one-dimensional (1D) nanostructures of Te, Se and Se-Te alloys directly from Te or/and Se powders. The products were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and scanning electron microscopy (SEM). Te nanorods and nanowires with a width varying from about 40 nm to about 300 nm, Se nanowires with a width of 60-100 nm and a length of 4-6 um, and SexTe100-x alloy nanorods with x in a wide range, and with a width of 30-70 nm and an aspect ratio of three to five, were prepared. The mechanism of formation of the nanorods and nanowires and the effects of the experimental conditions, such as solution concentration, cooling rate, solvent nature and heating process, on the morphology and size of the products have been discussed. We believe that this general route and some other proper reversible processes between solid state and solution state can be extended to the transformations from various bulk materials into nanosized materials with various morphologies. PMID- 26558592 TI - Aqueous colloidal processing of single-wall carbon nanotubes and their composites with ceramics. AB - A unique combination of acid treatment, aqueous colloidal processing, and spark plasma sintering (SPS) has been used to fabricate high-density Al2O3 /single-wall carbon nanotube (SWNT) composites with well-distributed SWNTs and other carbon nanostructures ('nano-onions', diamond) at Al2O3 grain boundaries. This approach could be used to obtain well-controlled microstructures of ceramic/SWNT composites for tailored mechanical, electrical, and thermal properties. In addition, the colloidal approach for dispersing SWNTs presented here could be used for the controlled manipulation of SWNTs. PMID- 26558593 TI - A nanomechanical device based on light-driven proton pumps. AB - In this paper, a hybrid device based on a microcantilever interfaced with bacteriorhodopsin (bR) is constructed. The microcantilever, on which the highly oriented bR film is self-assembled, undergoes controllable and reversible bending when the light-driven proton pump protein, bR, on the microcantilever surface is activated by visible light. Several control experiments are carried out to preclude the influence of heat and photothermal effects. It is shown that the nanomechanical motion is induced by the resulting gradient of protons, which are transported from the KCl solution on the cytoplasmic side of the bR film towards the extracellular side of the bR film. Along with a simple physical interpretation, the microfabricated cantilever interfaced with the organized molecular film of bR can simulate the natural machinery in converting solar energy to mechanical energy. PMID- 26558594 TI - Synthesis of hollow ZnO microspheres by an integrated autoclave and pyrolysis process. AB - Hollow zinc oxide microspheres have been synthesized from a micro ZnBr2.2H2O precursor obtained by an autoclave process in bromoform steam at 220 degrees C /2.5 MPa. Field-emission scanning electron microscropy (FE-SEM) and transmission electron microscopy (TEM) show that the products are about 1.0 um single crystal spherical particles with hollow interiors, partly open surfaces and walls self assembled by ZnO nanoparticles. X-ray diffraction (XRD) analysis shows that the as-prepared ZnO hollow spheres are of a hexagonal phase structure. A possible formation mechanism is suggested on the basis of the shape evolution of ZnO nanostructures observed by SEM and TEM. The room-temperature photoluminescence (PL) spectrum shows UV emission around 386 nm and weak green emission peaks indicating that there are few defects in the single crystal grains of the ZnO microspheres. PMID- 26558595 TI - Incorporating quantum dots into polymer microspheres via a spray-drying and thermal-denaturizing approach. AB - Bovine serum albumin (BSA) microspheres incorporated with CdTe quantum dots (QDs) have been prepared via a spray-drying and thermal-denaturizing approach. The results show that the morphology of the composites obtained was greatly affected by the inlet temperature and the initial concentration of BSA in the precursor. Most of the composites prepared with 0.6 mM BSA in the precursor at 40 degrees C were spherical in shape and hollow. The thermal-denaturized microspheres were water-insoluble, and separated from each other after dispersing in water. Each microsphere had bright fluorescence with pure colour. The microspheres without thermal-denaturation dissolved easily in water, and released nanospheres (>8 nm) that consisted of many CdTe nanoparticles (<3 nm). This approach opens the possibility of rapidly preparing QDs microspheres with controlled fluorescence intensity or with separated multiemission peaks for biomedical applications. PMID- 26558596 TI - Synthesis of single crystalline triangular and hexagonal Ni nanosheets with enhanced magnetic properties. AB - For the first time, single crystalline Ni nanosheets have been successfully synthesized with the aid of iron species. The as-prepared nanosheets are mainly triangular and hexagonal in shape, with edge lengths ranging from several tens to several hundreds of nanometres. The exposed sheet planes are assigned to be (111) planes of a face-centred cubic nickel crystal. The well defined geometry enhances the anisotropic energy of Ni nanosheets, and therefore increases its blocking temperature (TB) to room temperature. Notably, the coercive force of the Ni nanosheets is 172 Oe at 300 K, which is significantly higher than that of the bulk one (ca. 0.7 Oe at room temperature). A possible mechanism is proposed to explain the formation of the thermodynamically unfavorable morphology of nanosheets. We suggest that crystal twinning, which is formed by etching of the introduced iron species with oleic acid, lowers the system energy, and leads to the growth of these Ni nanosheets. PMID- 26558597 TI - Comment on 'Bi nanolines on Si(001): registry with substrate'. AB - A recent article (Miwa et al 2005 Nanotechnology 16 2427) casts doubt on the four dimer-wide Haiku model for the Bi nanoline on Si(001), suggesting instead that the three-dimer-wide Miki model (which had been ruled out) is a better fit in particular to x-ray data. The reasons why the Haiku model provides the best fit to all published data among currently proposed structures are discussed, concentrating on the width and registry of the Bi nanoline, and mentioning new data which shows that under appropriate conditions the two structures coexist in the same surface. PMID- 26558598 TI - Reply to Comment on 'Bi nanolines on Si(001): registry with the substrate'. AB - The registry of bismuth dimers, integral components of the bismuth nanoline on Si(001), is examined. In contrast to the currently accepted view, the bismuth dimers are found to be in registry with the two-dimensional lattice created by the silicon dimers. The consequences of this finding are briefly explored. PMID- 26558599 TI - Sm3S3BO3: The First Sulfide Borate without S-O and B-S Bonds. AB - An unprecedented quaternary sulfide borate, Sm3S3BO3 (1), was obtained via a high temperature solid-state synthesis method. It crystallizes in the triclinic space group P1, and its 3D structure features a 2D (Sm2S2)infinity wrinkled layer and a 1D (SmS)infinity ladderlike chain bridged by trigonal-planar (BO3)(3-) through Sm O bonds, demonstrating the first sulfide borate without S-O and B-S bonds. Its optical energy gap is measured to be around 2.5 eV and verified by electronic structure calculation. PMID- 26558600 TI - Women's and children's acceptance of biofortified quality protein maize for complementary feeding in rural Ethiopia. AB - BACKGROUND: For impact of nutritionally improved biofortified crops, consumer acceptance specifically by women and children is necessary when the target beneficiaries are young children. The objective was to assess women's and children's acceptance of a biofortified crop, quality protein maize (QPM), for complementary feeding in rural Ethiopia. RESULTS: Randomly sampled mothers (n = 61) of young children (6-24 months) evaluated flours from a QPM and a conventional maize variety for five sensory characteristics and overall acceptance by mother and child in a home use test with a double-blind, randomized controlled cross-over design. Women distinguished the varieties when used to prepare porridge, and QPM scored more favorably for texture in hand and mouth (both P < 0.05). The varieties did not differ in overall acceptance, which was, however, affected by order of presentation, mothers' number of children, and enumerators who collected data (all P < 0.05). Aroma and taste were key in mothers' acceptance, and appearance was further important for children. Women were more than twice as likely to prefer QPM over conventional maize. CONCLUSION: Consumer acceptance is unlikely to impede uptake and impact of QPM on young children's nutritional status. Home use testing proved feasible for assessing acceptance in rural areas with food insecurity and limited education. (c) 2015 Society of Chemical Industry. PMID- 26558601 TI - Direct C-H Allylation of N-Acyl/Sulfonyl Tetrahydroisoquinolines and Analogues. AB - A highly efficient direct C-H allylation reaction at the alpha position of N acyl/sulfonyl tetrahydroisoquinolines under mild conditions was developed. The reaction was also suitable for allylation of other protected nitrogen-containing heterocycles. Several interesting transformations of the products into valuable synthetic intermediates are featured with the successful total synthesis of (+/-) crispine A. PMID- 26558602 TI - Clinical, demographic and laboratory characteristics of methotrexate-responsive eczema. PMID- 26558603 TI - Stable integration and expression of a cry1Ia gene conferring resistance to fall armyworm and boll weevil in cotton plants. AB - BACKGROUND: Boll weevil is a serious pest of cotton crop. Effective control involves applications of chemical insecticides, increasing the cost of production and environmental pollution. The current genetically modified Bt crops have allowed great benefits to farmers but show activity limited to lepidopteran pests. This work reports on procedures adopted for integration and expression of a cry transgene conferring resistance to boll weevil and fall armyworm by using molecular tools. RESULTS: Four Brazilian cotton cultivars were microinjected with a minimal linear cassette generating 1248 putative lines. Complete gene integration was found in only one line (T0-34) containing one copy of cry1Ia detected by Southern blot. Protein was expressed in high concentration at 45 days after emergence (dae), decreasing by approximately 50% at 90 dae. Toxicity of the cry protein was demonstrated in feeding bioassays revealing 56.7% mortality to boll weevil fed buds and 88.1% mortality to fall armyworm fed leaves. A binding of cry1Ia antibody was found in the midgut of boll weevils fed on T0-34 buds in an immunodetection assay. CONCLUSION: The gene introduced into plants confers resistance to boll weevil and fall armyworm. Transmission of the transgene occurred normally to T1 progeny. All plants showed phenotypically normal growth, with fertile flowers and abundant seeds. (c) 2015 Society of Chemical Industry. PMID- 26558604 TI - Beclomethasone dipropionate hydrofluoroalkane for the treatment of allergic rhinitis. AB - Allergic rhinitis (AR) is a common respiratory disease, and its prevalence is increasing all over the world, both in adults and in children. Patients experience symptoms that may negatively impact on physical, social and psychological well-being. Hence, if left untreated, allergic rhinitis may significantly affect quality of life. Under current guidelines, intranasal corticosteroids are considered the most effective drugs and they are recommended as first-line therapy. Among the several corticosteroid intranasal sprays available, beclomethasone dipropionate is one of the most prescribed. Recently, new intranasal hydrofluoroalkane-propelled formulations with little or no impact on the ozone layer have been developed for the treatment of AR. The use of these devices might improve patients' adherence to treatment, avoiding some of the most common side effects associated with aqueous formulations. This review provides the most recent evidence for the efficacy and safety of beclomethasone dipropionate hydrofluoroalkane nasal aerosol in the treatment of allergic rhinitis. PMID- 26558606 TI - Comparative ontogeny of the feeding apparatus of sympatric drums (Perciformes: Sciaenidae) in the Chesapeake Bay. AB - The anatomy of the feeding apparatus in fishes, including both oral and pharyngeal jaw elements, is closely related to the ecology of a species. During ontogeny, the oral and pharyngeal jaws undergo dramatic changes. To better understand how such ontogenetic changes occur and relate to the feeding ecology of a species, ontogenetic series of four closely related members of the family Sciaenidae (Cynoscion nebulosus, Cynoscion regalis, Micropogonias undulatus, and Leiostomus xanthurus) were examined. Sciaenids were selected because as adults they exhibit considerable specialization of the feeding apparatus correlated with differences in foraging habitats. However, it is not clear when during ontogeny the structural specializations of the feeding apparatus develop, and thereby enable early life history stage (ELHS) sciaenids to partition their foraging habitats. A regression tree was recovered from the analysis and three divergences were identified during ontogeny. There are no measurable differences in elements of the feeding apparatus until the first divergence at 8.4 mm head length (HL), which was attributed to differences in average gill filament length on the second ceratobranchial. The second divergence occurred at 14.1 mm HL and was associated with premaxilla length. The final divergence occurred at 19.8 mm HL and was associated with differences in the toothed area of the fifth certatobranchial. These morphological divergences suggest that ELHS sciaenids may be structurally able to partition their foraging habitats as early as 8.4 mm HL. PMID- 26558605 TI - Array-Based Platform To Select, Release, and Capture Epstein-Barr Virus-Infected Cells Based on Intercellular Adhesion. AB - Microraft arrays were developed to select and separate cells based on a complex phenotype, weak intercellular adhesion, without knowledge of cell-surface markers or intracellular proteins. Since the cells were also not competent to bind to a culture surface, a method to encapsulate nonadherent cells within a gelatin plug on the concave microraft surface was developed, enabling release and collection of the cells without the need for cell attachment to the microraft surface. After microraft collection, the gelatin was liquified to release the cell(s) for culture or analysis. A semiautomated release and collection device for the microrafts demonstrated 100 +/- 0% collection efficiency of the microraft while increasing throughput 5-fold relative to that of manual release and collection. Using the microraft array platform along with the gelatin encapsulation method, single cells that were not surface-attached were isolated with a 100 +/- 0% efficiency and a 96 +/- 4% postsort single-cell cloning efficiency. As a demonstration, Epstein-Barr virus-infected lymphoblastoid cell lines (EBV-LCL) were isolated based on their intercellular adhesive properties. The identified cell colonies were collected with a 100 +/- 0% sorting efficiency and a postsort viability of 87 +/- 3%. When gene expression analysis of the EBV latency associated gene, EBNA-2, was performed, there was no difference in expression between blasting or weakly adhesive cells and nonblasting or nonadhesive cells. Microraft arrays are a versatile method enabling separation of cells based on complicated and as yet poorly understood cell phenotypes. PMID- 26558607 TI - Real Colorimetric Thrombin Aptasensor by Masking Surfaces of Catalytically Active Gold Nanoparticles. AB - We presented a simple, cost-effective, and ultrasensitive colorimetric approach for visually detecting thrombin by the catalytic amplification of gold nanoparticles (AuNPs) and aptamer-thrombin recognition. Thrombin can be quantified in the presence of catalytic AuNP surface by using color-change time of 4-nitrophenol. Without thrombin, yellow 4-nitrophenol can freely access the surface of AuNP and becomes colorless 4-aminophenol. With the addition of thrombin, aptamer-thrombin with large size interaction masks the partial surfaces of AuNPs, and increases the reduction time of 4-nitrophenol to 4-aminophenol. The maximum number of bound thrombin fully mask the catalytic AuNP surface, and thus 4-nitrophenol cannot approach to AuNP surface, the color of the solution remains yellow. The limit of detection (LOD) of 0.1 nM can be achieved with naked eyes. Of note, the method was further applied for the detection of thrombin in human serum samples, showing the results in agreement with those values obtained in an immobilization buffer by the colorimetric method. PMID- 26558608 TI - Correction: Genome-Wide Survey and Expression Analysis of Chlamydomonas reinhardtii U-box E3 Ubiquitin Ligases (CrPUBs) Reveal a Functional Lipid Metabolism Module. PMID- 26558609 TI - Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization. AB - Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35-40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells. PMID- 26558610 TI - Making Time for Nature: Visual Exposure to Natural Environments Lengthens Subjective Time Perception and Reduces Impulsivity. AB - Impulsivity in delay discounting is associated with maladaptive behaviors such as overeating and drug and alcohol abuse. Researchers have recently noted that delay discounting, even when measured by a brief laboratory task, may be the best predictor of human health related behaviors (e.g., exercise) currently available. Identifying techniques to decrease impulsivity in delay discounting, therefore, could help improve decision-making on a global scale. Visual exposure to natural environments is one recent approach shown to decrease impulsive decision-making in a delay discounting task, although the mechanism driving this result is currently unknown. The present experiment was thus designed to evaluate not only whether visual exposure to natural (mountains, lakes) relative to built (buildings, cities) environments resulted in less impulsivity, but also whether this exposure influenced time perception. Participants were randomly assigned to either a natural environment condition or a built environment condition. Participants viewed photographs of either natural scenes or built scenes before and during a delay discounting task in which they made choices about receiving immediate or delayed hypothetical monetary outcomes. Participants also completed an interval bisection task in which natural or built stimuli were judged as relatively longer or shorter presentation durations. Following the delay discounting and interval bisection tasks, additional measures of time perception were administered, including how many minutes participants thought had passed during the session and a scale measurement of whether time "flew" or "dragged" during the session. Participants exposed to natural as opposed to built scenes were less impulsive and also reported longer subjective session times, although no differences across groups were revealed with the interval bisection task. These results are the first to suggest that decreased impulsivity from exposure to natural as opposed to built environments may be related to lengthened time perception. PMID- 26558611 TI - Drug Susceptibility Patterns in MDR-TB Patients: Challenges for Future Regimen Design. A Cross-Sectional Study. AB - Globally, there is substantial concern regarding the challenges of treating complex drug resistance patterns in multidrug resistant tuberculosis cases. Utilising data from three different settings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles for multidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen, and inform future regimen selection. Demographic and microbiological surveillance data for multidrug resistant tuberculosis cases from 2004-13 were analysed. High levels of additional resistance to currently recommended second line drugs were seen in all settings, with extensive variability between countries. Accurate drug susceptibility testing and drug susceptibility testing data are vital to inform the development of comprehensive, flexible, multidrug resistant tuberculosis guidance. PMID- 26558613 TI - QSAR studies in the discovery of novel type-II diabetic therapies. AB - INTRODUCTION: Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. AREAS COVERED: This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. EXPERT OPINION: Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies. PMID- 26558614 TI - miRLocator: Machine Learning-Based Prediction of Mature MicroRNAs within Plant Pre-miRNA Sequences. AB - MicroRNAs (miRNAs) are a class of short, non-coding RNA that play regulatory roles in a wide variety of biological processes, such as plant growth and abiotic stress responses. Although several computational tools have been developed to identify primary miRNAs and precursor miRNAs (pre-miRNAs), very few provide the functionality of locating mature miRNAs within plant pre-miRNAs. This manuscript introduces a novel algorithm for predicting miRNAs named miRLocator, which is based on machine learning techniques and sequence and structural features extracted from miRNA:miRNA* duplexes. To address the class imbalance problem (few real miRNAs and a large number of pseudo miRNAs), the prediction models in miRLocator were optimized by considering critical (and often ignored) factors that can markedly affect the prediction accuracy of mature miRNAs, including the machine learning algorithm and the ratio between training positive and negative samples. Ten-fold cross-validation on 5854 experimentally validated miRNAs from 19 plant species showed that miRLocator performed better than the state-of-art miRNA predictor miRdup in locating mature miRNAs within plant pre-miRNAs. miRLocator will aid researchers interested in discovering miRNAs from model and non-model plant species. PMID- 26558612 TI - Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases. AB - Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library(r) and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics based substructure analyses-using the rotationally constrained carboxylate in R naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R naproxen and R-ketorolac have potential for rapid translation and efficacy in the treatment of several epithelial cancer types on account of established human toxicity profiles and novel activities against Rho-family GTPases. PMID- 26558615 TI - Similarity to the self influences cortical recruitment during impression formation. AB - Prior work has shown that whether or not someone is similar to the self influences person memory--a type of self-reference effect for others. In this study, we were interested in understanding the neural regions supporting the generation of impressions and subsequent memory for targets who vary in similarity to the self. Participants underwent fMRI scanning while forming positive or negative impressions of face-behavior pairs. We tested participants' memory for their generated impressions and then back-sorted the impression trials (encoding) into different levels of self-similarity (high, medium, low) using a self-similarity posttest that came after recognition. Extending prior behavioral work, our data confirmed our hypothesis that memory would be highest for self similar others and lowest for self-dissimilar others. Dorsal anterior cingulate cortex (dACC) activity increased with self-similarity (high > medium > low) to targets, regardless of later memory for them. An analysis of regions supporting impression memory revealed a double dissociation within medial temporal lobe regions: for similar others, amygdala recruitment supported memory, whereas for dissimilar others, hippocampal activation supported memory. These results suggest that self-similarity influences evaluation and memory for targets but also affects the underlying neural resources engaged when thinking about others who vary in self-similarity. PMID- 26558616 TI - Network Events on Multiple Space and Time Scales in Cultured Neural Networks and in a Stochastic Rate Model. AB - Cortical networks, in-vitro as well as in-vivo, can spontaneously generate a variety of collective dynamical events such as network spikes, UP and DOWN states, global oscillations, and avalanches. Though each of them has been variously recognized in previous works as expression of the excitability of the cortical tissue and the associated nonlinear dynamics, a unified picture of the determinant factors (dynamical and architectural) is desirable and not yet available. Progress has also been partially hindered by the use of a variety of statistical measures to define the network events of interest. We propose here a common probabilistic definition of network events that, applied to the firing activity of cultured neural networks, highlights the co-occurrence of network spikes, power-law distributed avalanches, and exponentially distributed 'quasi orbits', which offer a third type of collective behavior. A rate model, including synaptic excitation and inhibition with no imposed topology, synaptic short-term depression, and finite-size noise, accounts for all these different, coexisting phenomena. We find that their emergence is largely regulated by the proximity to an oscillatory instability of the dynamics, where the non-linear excitable behavior leads to a self-amplification of activity fluctuations over a wide range of scales in space and time. In this sense, the cultured network dynamics is compatible with an excitation-inhibition balance corresponding to a slightly sub critical regime. Finally, we propose and test a method to infer the characteristic time of the fatigue process, from the observed time course of the network's firing rate. Unlike the model, possessing a single fatigue mechanism, the cultured network appears to show multiple time scales, signalling the possible coexistence of different fatigue mechanisms. PMID- 26558617 TI - The effects of pharmacological modulation of the serotonin 2C receptor on goal directed behavior in mice. AB - RATIONALE: Impaired goal-directed motivation represents a debilitating class of symptoms common to psychological disorders including schizophrenia and some affective disorders. Despite the known negative impact of impaired motivation, there are currently no effective pharmacological interventions to treat these symptoms. OBJECTIVES: Here, we evaluate the effectiveness of the serotonin 2C (5 HT2C) receptor selective ligand, SB242084, as a potential pharmacological intervention for enhancing goal-directed motivation in mice. The studies were designed to identify not only efficacy but also the specific motivational processes that were affected by the drug treatment. METHODS: We tested subjects following treatment with SB242084 (0.75 mg/kg) in several operant lever pressing assays including the following: a progressive ratio (PR) schedule of reinforcement, an effort-based choice task, a progressive hold down task (PHD), and various food intake tests. RESULTS: Acute SB242084 treatment leads to an increase in instrumental behavior. Using a battery of behavioral tasks, we demonstrate that the major effect of SB242084 is an increase in the amount of responses and duration of effort that subjects will make for food rewards. This enhancement of behavior is not the result of non-specific hyperactivity or arousal nor is it due to changes in food consumption. CONCLUSIONS: Because of this specificity of action, we suggest that the 5-HT2C receptor warrants further attention as a novel therapeutic target for treating pathological impairments in goal-directed motivation. PMID- 26558618 TI - Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4 methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d amphetamine + MDMA mixture. AB - RATIONALE: Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4 methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. OBJECTIVES: The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. METHODS: Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. RESULTS: Dose response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. CONCLUSIONS: These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone. PMID- 26558619 TI - Serotonin (5-HT)1A receptor agonism and 5-HT7 receptor antagonism ameliorate the subchronic phencyclidine-induced deficit in executive functioning in mice. AB - RATIONALE: Reversal learning (RL), a type of executive function, dependent on prefrontal cortical function, is impaired in rodents by subchronic (sc) treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), a widely studied model of cognitive impairment in schizophrenia (CIS). OBJECTIVE: The principal objective of this study was to determine the ability of serotonin (5 HT)1A partial agonism and 5-HT7 receptor antagonism to improve RL in scPCP treated mice. METHODS: Male C57BL/6J mice were trained on an operant RL (ORL) task, then received PCP, 10 mg/kg, or saline, bid, for 7 days, followed by a 7 day washout period. RESULTS: scPCP significantly diminished the percent correct responding, increased total incorrect trials, and total incorrect responses, in the reversal phase performance of the ORL task. Pre-treatment with the selective 5-HT1A partial agonist, tandospirone, or the selective 5-HT7 antagonist, SB269970, but not the 5-HT7 agonist, AS 19, reversed the scPCP-induced deficit in RL. Pre-treatment with atypical antipsychotic drug lurasidone, which is a 5-HT1A partial agonist and 5-HT7 antagonist, as well as a 5-HT2A and dopamine (D)2 antagonist, also reversed RL deficit in the scPCP-treated mice. Furthermore, the selective 5-HT1A antagonist, WAY100635, blocked the ability of lurasidone to reverse the scPCP-induced RL deficit. CONCLUSIONS: These results indicate that 5 HT7 antagonism and 5-HT1A partial agonism contribute to restoration of RL in scPCP-treated mice. It is suggested that these two mechanisms are effective in restoring RL by decreasing excessive GABAergic inhibition of cortical pyramidal neurons following withdrawal of scPCP treatment. PMID- 26558620 TI - Effects of fatty acid amide hydrolase (FAAH) inhibitors on working memory in rats. AB - RATIONALE: Manipulations of the endocannabinoid system could potentially produce therapeutic effects with minimal risk of adverse cannabis-like side effects. Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of the cannabinoid-receptor agonist, anandamide, and show promise for treating a wide range of disorders. However, their effects on learning and memory have not been fully characterized. OBJECTIVES: We determined the effects of five structurally different FAAH inhibitors in an animal model of working memory known to be sensitive to impairment by delta-9 tetrahydrocannabinol (THC). METHODS: A delayed nonmatching-to-position procedure was used in rats. Illuminated nosepoke holes were used to provide sample cues (left versus right) and record responses (correct versus incorrect) after delays ranging from 0 to 28 s. Various test drugs were given acutely up to two times per week before daily sessions. RESULTS: One FAAH inhibitor, AM3506 (3 mg/kg), decreased accuracy in the memory task. Four other FAAH inhibitors (URB597, URB694, PF-04457845, and ARN14633) and a monoacylglycerol lipase inhibitor (JZL184, which blocks the degradation of the endocannabinoid 2-arachidonoylglycerol) had no effect. Testing of AM3506 in combination with antagonists for receptors known to be affected by anandamide and other fatty acid amides indicated that the impairment induced by AM3506 was mediated by cannabinoid CB1 receptors, and not by alpha-type peroxisome proliferator-activated receptors (PPAR-alpha) or vanilloid transient receptor potential cation channels (TRPV1). CONCLUSIONS: FAAH inhibitors differ with respect to their potential for memory impairment, abuse liability, and probably other cannabis-like effects, and they should be evaluated individually for specific therapeutic and adverse effects. PMID- 26558621 TI - Non-Adrenergic Vasopressors in Patients with or at Risk for Vasodilatory Shock. A Systematic Review and Meta-Analysis of Randomized Trials. AB - INTRODUCTION: Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality. METHODS: PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, non-human studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available. RESULTS: A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95% confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction in mortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias. CONCLUSIONS: Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding. PMID- 26558622 TI - Prevalence of toxoplasmosis in pregnant women and vertical transmission of Toxoplasma gondii in patients from basic units of health from Gurupi, Tocantins, Brazil, from 2012 to 2014. AB - INTRODUCTION: Toxoplasmosis is a parasitary disease that presents high rates of gestational and congenital infection worldwide being therefore considered a public health problem and a neglected disease. OBJECTIVE: To determine the prevalence of toxoplasmosis amongst pregnant women and vertical transmission of Toxoplasma gondii in their newborns attended in the Basic Units of Health (BUH) from the city of Gurupi, state of Tocantins, Brazil. METHODS: A prevalence study was performed, including 487 pregnant women and their newborns attended in the BUH of the urban zone of the city of Gurupi, state of Tocantins, Brazil, during the period from February 2012 to February 2014. The selection of the pregnant women occurred by convenience. In the antenatal admission they were invited to participate in this study. Three samples of peripheral blood were collected for the detection of specific anti-T. gondii IgG, IgM and IgA through ELISA, for the polimerase chain reaction (PCR) and IgG avidity during pregnancy. When IgM antibodies were detected the fetal and newborn infection investigation took place. The newborn was investigated right after birth and after one year of age through serology and PCR to confirm/exclude the vertical transmission. The analyses were performed in the Studies of the Host-Parasite Relationship Laboratory (LAERPH, IPTSP-UFG), Goiania, state of Goias, Brazil. The results were inserted in a data bank in Epi-Info 3.3.2 statistic software in which the analysis was performed with p<=5%. RESULTS: The toxoplasmosis infection was detected in 68.37% (333/487, CI95%: 64.62-72.86). The toxoplasmosis chronic infection prevalence was of 63.03% (307/487, CI95%: 58.74-67.32). The prevalence of maternal acute infection was of 5.33% (26/487; CI95%: 3.3-7.3) suspected by IgM antibodies detection in the peripheral blood. The prevalence of confirmed vertical transmission was of 28% (7/25; CI95%: 10.4-45.6). CONCLUSIONS: These results show an elevated prevalence of toxoplasmosis in pregnant women and vertical transmission of T. gondii in the city of Gurupi, state of Tocantins, Brazil. PMID- 26558623 TI - [S3 guidelines on long-term opioid treatment in non-cancer pain. Recommendations for opioid use in clinical rheumatology]. AB - The long-term use of opioids for chronic pain can be problematic in many respects. Besides potentially harmful and considerable undesired side effects and possible drug abuse, the indications for prescription, efficacy and safety in the long run have to be considered. The recently updated S3 guidelines on long-term opioid treatment in non-cancer pain (LONTS) provide recommendations with the highest currently available evidence. This article summarizes the most relevant contents for the clinical rheumatologist. PMID- 26558624 TI - Heterogeneity in prey distribution allows for higher food intake in planktivorous fish, particularly when hot. AB - When prey are scarce, planktivorous fish and other predators feeding on tiny prey should forage within prey-rich patches to attain a net food intake above the ambient mean food concentrations. If they can indeed locate prey-rich patches efficiently, then a patchy distribution of planktonic prey should lead to: (1) an increase in the overall per capita food intake, and (2) greater variability among predators in prey-capture rate due to differences in arrival times. Both phenomena were observed in 34 daily feeding sessions with a cohort of juvenile rudd held in twin experimental systems, each housing the same number of fish free to move in a loop of ten interconnected 200-L tanks. The fish were fed daily with equal numbers of planktonic prey (Artemia nauplii), offered either in a homogeneous or patchy distribution. To simulate low and high temperatures that represent potential global warming scenarios, the feeding protocol was replicated at 16, 21 and 26 degrees C, on each occasion following a 3-day period of fish acclimation. Up to 40-70 % of fish in the system with the patchy prey distribution assembled rapidly in the high-prey-density tank, the capture rate of first arrivals being up to 60 prey min(-1) at 26 degrees C, orders of magnitude greater than that of latecomers. The overall capture rates were higher in the system with patchy prey, regardless of the temperature. At the highest temperature (26 degrees C), the fish located the high-prey-density tank in less than half the time taken at the lowest temperature (16 degrees C, Q(10) > 2). PMID- 26558625 TI - Impact of change in winter strategy of one parasitoid species on the diversity and function of a guild of parasitoids. AB - The rise of temperatures may enable species to increase their activities during winter periods and to occupy new areas. In winter, resource density is low for most species and an increased number of active consumers during this season may produce heightened competitive pressure. In Western France, the aphid parasitoid species Aphidius avenae Haliday has been known to adopt a winter diapausing strategy adjacent to newly sown cereal crops, until recent reports of active winter populations in cereal crops. We investigate how the addition of this species to the winter guild of parasitoids may change the structure of the aphid parasitoid food web and the host-exploitation strategies of previously occurring parasitoids. We showed that in winter, Aphidius avenae was mostly associated with two aphid species, Sitobion avenae Fabricius and Metopolophium dirhodum Walker, while the generalist species Aphidius rhopalosiphi was restricted to the aphid species Rhopalosiphum padi L. in the presence of Aphidius avenae. Due to this new competition, winter food webs present a higher degree of compartmentalization and lower proportional similarity index values than spring ones. Parasitoid and aphid abundances responded significantly to changes in daily high temperatures, suggesting that the host-parasitoid community structure can be partly predicted by climate. This study demonstrates how a change in the winter strategy of one species of a guild can modify complex interspecific relationships in host parasitoid systems. PMID- 26558627 TI - Tax evading retired surgeon is struck off for "prolonged dishonesty". PMID- 26558626 TI - Population pharmacokinetics of ramosetron. AB - Ramosetron is a selective serotonergic 5-hydroxy-tryptamine receptor 3 antagonist that is used to prevent and treat postoperative nausea and vomiting. This study aimed to characterize the population pharmacokinetics of ramosetron in patients undergoing surgery with general anesthesia. Patients aged 19-80 years received a single intravenous bolus of ramosetron (0.3, 0.45, or 0.6 mg) 30 min before the end of surgery. Blood samples were collected, and plasma concentrations of ramosetron were measured by high performance liquid chromatography-tandem mass spectrometry. Pooled data from 50 patients and 479 pharmacokinetic samples were used for population pharmacokinetic analysis using the nonlinear mixed effect modeling program (NONMEM((r))). The pharmacokinetics of ramosetron was best described by a three-compartment mammillary model with first-order elimination. Based on allometric principles, body weight was incorporated in the base model, along with fixed allometric exponents. The typical value of clearance was 0.19 L/h in a 60-kg subject, and it decreased approximately 3% for every year of age, starting at age of 57. The bootstrap method and visual predictive check showed that the final pharmacokinetic model was appropriate. A population pharmacokinetic model of ramosetron was constructed in adult surgical patients, providing a foundation for further defining the relationship between ramosetron dose and postoperative nausea and vomiting. PMID- 26558628 TI - Community Sexual Bridging Among Heterosexuals at High-Risk of HIV in New York City. AB - Community sexual bridging may influence the socio-geographic distribution of heterosexually transmitted HIV. In a cross-sectional study, heterosexual adults at high-risk of HIV were recruited in New York City (NYC) in 2010 for the Centers for Disease Control and Prevention-sponsored National HIV Behavioral Surveillance system. Eligible participants were interviewed about their HIV risk behaviors and sexual partnerships and tested for HIV. Social network analysis of the geographic location of participants' recent sexual partnerships was used to calculate three sexual bridging measures (non-redundant ties, flow-betweenness and walk betweenness) for NYC communities (defined as United Hospital Fund neighborhoods), which were plotted against HIV prevalence in each community. The analysis sample comprised 494 participants and 1534 sexual partnerships. Participants were 60.1 % male, 79.6 % non-Hispanic black and 19.6 % Hispanic race/ethnicity; the median age was 40 years (IQR 24-50); 37.7 % had ever been homeless (past 12 months); 16.6 % had ever injected drugs; in the past 12 months 76.7 % used non-injection drugs and 90.1 % engaged in condomless vaginal or anal sex; 9.6 % tested HIV positive (of 481 with positive/negative results). Sexual partnerships were located in 33 (78.6 %) of 42 NYC communities, including 13 "high HIV-spread communities", 7 "hidden bridging communities", 0 "contained high HIV prevalence communities", and 13 "latent HIV bridging communities". Compared with latent HIV bridging communities, the population racial/ethnic composition was more likely (p < 0.0001) to be black or Hispanic in high HIV-spread communities and to be black in hidden bridging communities. High HIV-spread and hidden bridging communities may facilitate the maintenance and spread of heterosexually transmitted HIV in black and Hispanic populations in NYC. PMID- 26558629 TI - Associations Between Drug and Alcohol Use Patterns and Sexual Risk in a Sample of African American Men Who Have Sex with Men. AB - Men who have sex with men (MSM) are the largest risk group in the US HIV epidemic and African American MSM (AA MSM) are disproportionately affected. Substance abusing sexual minorities warrant attention as they are at elevated risk for HIV, yet are not a homogeneous risk group. The purpose of this study was to use latent class analysis to identify patterns of drug and alcohol use in a sample of 359 AA MSM and examine associations with sexual risk. Three classes were identified: Individuals who used multiple substances (poly-users) (18 %), alcohol/marijuana users (33 %) and individuals who had low probability of reporting drug or problematic alcohol use (50 %). Results from multivariate analysis indicate that poly-users were older and more likely to report sex exchange and recent sexually transmitted infection compared to the other classes. Alcohol and poly-users were more likely to report sex under the influence. Identifying and defining substance use patterns can improve specification of risk groups and allocation of prevention resources. PMID- 26558630 TI - Evaluation of the Role of JNK1 in the Hippocampus in an Experimental Model of Familial Alzheimer's Disease. AB - c-Jun N-terminal kinases (JNKs), which belong to a mitogen-activated protein kinase (MAPK) family, are involved in the regulation of several physiological functions in mammals and act as mediators of apoptosis, obesity, and memory storage in the brain, including the processes of neuronal de- and regeneration. JNK subfamily is encoded by three separate but related genes: jnk1, jnk2, and jnk3, giving rise to at least ten distinct splice variants of the JNK proteins. JNK3 is thought to be a major contributor to neurodegeneration in mammalian brain. The role of JNK1 in the pathological processes affecting cognitive function, especially in diseases such as Alzheimer's disease (AD), is less clear. In order to evaluate the effects of JNK1 deficiency in an experimental model of familial Alzheimer's disease, double transgenic APPswe/PS1dE9 mice were crossed with the JNK1 heterozygous deficient animals (jnk1+/-). As expected, a ~50 % reduction in JNK1 protein levels was observed in the hippocampi of 9-month-old APPswe/PS1dE9/jnk1+/- mice, compared with the APPswe/PS1dE9 group. JNK1 deficiency resulted in reduced BACE1 expression, suggesting alterations in amyloidogenic pathway. However, no significant inter-group differences in the total number of beta-amyloid plaques were observed in the hippocampal region. In addition, protein levels of PPAR gamma coactivator-1alpha (PGC-1alpha), a molecule involved in mitochondrial biogenesis and energy homeostasis, were decreased in 9-month-old APPswe/PS1dE9 mice but not in APPswe/PS1dE9/jnk1+/- animals. Furthermore, JNK1 deficiency did not have an effect on pro-inflammatory marker expression in the hippocampus. Heterozygous deficiency of JNK1 results in the decrease of BACE1 protein levels, which is not accompanied by the reduction in the total number of beta-amyloid plaques in the hippocampi of APPswe/PS1dE9 mice. Moreover, PGC-1alpha expression is restored in APPswe/PS1dE9/jnk1+/- animals, which indicates a possible role of JNK1 in brain mitochondrial regulation. Nevertheless, our results suggest that partial inhibition of JNK1 is not sufficient to prevent the neuropathological processes in this model. It may be necessary to inhibit both the JNK1 and JNK3 simultaneously, especially as previous studies suggest that JNK3 contributes to AD neuropathology. PMID- 26558632 TI - Proliferating Cell Nuclear Antigen Has an Association with Prognosis and Risks Factors of Cancer Patients: a Systematic Review. AB - Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71-7.17, p = 0.000; HR = 4.40, 95 % CI 3.00 6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48 5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15-7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71-1.43, p = 0.957; OR = 1.00, 95 % CI 0.80-1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers. PMID- 26558631 TI - Rotenone Induces the Formation of 4-Hydroxynonenal Aggresomes. Role of ROS Mediated Tubulin Hyperacetylation and Autophagic Flux Disruption. AB - Oxidative stress causes cellular damage by (i) altering protein stability, (ii) impairing organelle function, or (iii) triggering the formation of 4-HNE protein aggregates. The catabolic process known as autophagy is an antioxidant cellular response aimed to counteract these stressful conditions. Therefore, autophagy might act as a cytoprotective response by removing impaired organelles and aggregated proteins. In the present study, we sought to understand the role of autophagy in the clearance of 4-HNE protein aggregates in ARPE-19 cells under rotenone exposure. Rotenone induced an overproduction of reactive oxygen species (ROS), which led to an accumulation of 4-HNE inclusions, and an increase in the number of autophagosomes. The latter resulted from a disturbed autophagic flux rather than an activation of the autophagic synthesis pathway. In compliance with this, rotenone treatment induced an increase in LC3-II while upstream autophagy markers such as Beclin- 1, Vsp34 or Atg5-Atg12, were decreased. Rotenone reduced the autophagosome-to-lysosome fusion step by increasing tubulin acetylation levels through a ROS-mediated pathway. Proof of this is the finding that the free radical scavenger, N-acetylcysteine, restored autophagy flux and reduced rotenone induced tubulin hyperacetylation. Indeed, this dysfunctional autophagic response exacerbates cell death triggered by rotenone, since 3-methyladenine, an autophagy inhibitor, reduced cell mortality, while rapamycin, an inductor of autophagy, caused opposite effects. In summary, we shed new light on the mechanisms involved in the autophagic responses disrupted by oxidative stress, which take place in neurodegenerative diseases such as Huntington or Parkinson diseases, and age related macular degeneration. PMID- 26558633 TI - Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration. AB - The expression of matrix metalloproteinase-13 (MMP-13) has been shown to be elevated in some pathophysiological conditions and is involved in the degradation of extracellular matrix in astrocytes. In current study, the function of MMP-13 was further investigated. The conditioned medium (CM) collected from activated microglia increased interleukin (IL)-18 production and enhanced MMP-13 expression in astrocytes. Furthermore, treatment with recombinant IL-18 increased MMP-13 protein and mRNA levels in astrocytes. Recombinant IL-18 stimulation also increased the enzymatic activity of MMP-13 and the migratory activity of astrocytes, while administration of MMP-13 or pan-MMP inhibitors antagonized IL 18-induced migratory activity of astrocytes. In addition, administration of recombinant IL-18 to astrocytes led to the phosphorylation of JNK, Akt, or PKCdelta, and treatment of astrocytes with JNK, PI3 kinase/Akt, or PKCdelta inhibitors significantly decreased the IL-18-induced migratory activity. Taken together, the results suggest that IL-18-induced MMP-13 expression in astrocytes is regulated by JNK, PI3 kinase/Akt, and PKCdelta signaling pathways. These findings also indicate that IL-18 is an important regulator leading to MMP-13 expression and cell migration in astrocytes. PMID- 26558635 TI - Use of Candida antigen injections for the treatment of verruca vulgaris: A two year mayo clinic experience. AB - Common warts (verruca vulgaris) are one of the most common problems encountered in dermatology and may present a difficult treatment dilemma, as no particular therapy has demonstrated complete efficacy. Intralesional injection of purified Candida antigen has produced impressive treatment results in small prospective and retrospective studies and is thought to produce its effect through stimulation of a cell-mediated immune response. We report a retrospective study of adult and pediatric patients treated with Candida antigen therapy in clinical practice. Of the 100 patients treated, 80% responded to therapy: 39% demonstrated a complete response and 41% demonstrated a partial response. In addition, 6 out of 7 immunocompromised patients who were treated demonstrated a partial or complete response. Injections were generally well-tolerated and adverse events were minimal and short-lived. Our data indicate that intralesional Candida antigen therapy for cutaneous warts is an efficacious option in a clinical practice setting. The treatment may also be effective in immunosuppressed patients with cutaneous warts. Our results add to the literature one of the largest retrospective series reported to date and treatment outcomes are similar to previously reported studies evaluating this therapeutic modality. PMID- 26558634 TI - Iron Loading Selectively Increases Hippocampal Levels of Ubiquitinated Proteins and Impairs Hippocampus-Dependent Memory. AB - Alterations of brain iron levels have been observed in a number of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in the adulthood. Protein degradation mediated by the ubiquitin-proteasome system (UPS) plays a central regulatory role in several cellular processes. Impairment of the UPS has been implicated in the pathogenesis of neurodegenerative disorders. Here, we examined the effects of iron exposure in the neonatal period (12th-14th day of postnatal life) on the expression of proteasome beta-1, beta-2, and beta-5 subunits, and ubiquitinated proteins in brains of 15-day-old rats, to evaluate the immediate effect of the treatment, and in adulthood to assess long-lasting effects. Two different memory types, emotionally motivated conditioning and object recognition were assessed in adult animals. We found that iron administered in the neonatal period impairs both emotionally motivated and recognition memory. Polyubiquitinated protein levels were increased in the hippocampus, but not in the cortex, of adult animals treated with iron. Gene expression of subunits beta1 and beta5 was affected by age, being higher in the early stages of development in the hippocampus, accompanied by an age-related increase in polyubiquitinated protein levels in adults. In the cortex, gene expression of the three proteasome subunits was significantly higher in adulthood than in the neonatal period. These findings suggest that expression of proteasome subunits and activity are age-dependently regulated. Iron exposure in the neonatal period produces long-lasting harmful effects on the UPS functioning, which may be related with iron-induced memory impairment. PMID- 26558636 TI - Examining the impact of formal planning on performance in older adults using a naturalistic task paradigm. AB - Thirty-two younger adults (YAs) and 64 older adults (OAs) completed the Amap Task, a naturalistic measure designed to evaluate the formulation and execution stages of planning. Participants read a map layout of a university apartment and planned an efficient strategy to complete several tasks. To determine whether execution abilities are augmented by formulating a plan, we compared formal (i.e., written strategy) and informal (i.e., initiate task when ready without writing out a strategy) planning conditions. Participants did not have access to their plan during task execution. Amap scores were also compared with informant report of everyday functioning. For the formal planning condition, OAs were less accurate and less efficient than YAs during the formulation stage, while there were no group differences in total formulation time for the informal planning condition. Across conditions, OAs obtained poorer execution accuracy and efficiency scores, took longer during execution, and omitted more task parts. Formal planning improved execution efficiency but not accuracy, suggesting one's approach to the task (i.e., efficiency, finesse) may improve with preplanning even if overall accuracy does not. Significant relationships between Amap scores and informant-report of everyday functioning highlight the ecological validity of the Amap as a measure sensitive to everyday planning abilities. PMID- 26558637 TI - The 2015 C. H. McCloy Lecture: Road Trip Toward More Inclusive Physical Activity: Maps, Mechanics, Detours, and Traveling Companions. AB - This essay stems from the 35th annual C. H. McCloy Research Lecture at the 2015 SHAPE America National Convention & Expo in Seattle, WA. The lecture series has 2 main aims. First, it provides an annual forum for a contemporary scholar to delve deeply into her/his work and to share that work with her/his peers. Second, it is an enduring tribute to the pioneering work and influential career of Charles Henry McCloy (March 30, 1886-September 18, 1959), research professor emeritus at the University of Iowa. This essay is composed of 6 sections: a prologue, a biography of McCloy, my autobiography, the fundamental premises and overarching aims of my work, a summary of my research contributions aimed at promoting inclusive physical activity, and an epilogue. The entire article is built around the construct of maps, mechanics, detours, and traveling companions. Paradigm shifts and insights are unraveled as the work unfolds and becomes increasingly integrated. Rarely does a scholar have the chance to provide a narrative of this nature, and it is hoped that this essay will inspire others to discover their own scholarly pathways and to contextualize and reflect on their contributions for the greater good of the field of kinesiology and society. PMID- 26558638 TI - Optimizing the Role of Physical Education in Promoting Physical Activity: A Social-Ecological Approach. AB - The benefits associated with being physically active are well documented, but a significant proportion of the population is insufficiently active. Physical inactivity is a major health risk factor in our society, and physical education programs are consistently identified as a means to address this concern. The purpose of this article is to use the social-ecological model as a framework to examine ways in which physical education programs can play an important role in promoting physical activity. Policies that require time allocations and resources for physical education and physical activity in schools and community designs that provide infrastructure that makes being physically active accessible and convenient are important factors in making schools and communities healthier spaces. It is clear, however, that policies alone are not sufficient to address concerns about physical inactivity. We must consider individual factors that influence decisions to be physically active in efforts to engage children in physical education programs that promote active lifestyles. The learning climate that teachers create determines what students do and learn in physical education classes. Ensuring that students see value in the content presented and structuring classes so that students believe they can experience success when they exert effort are key elements in an effective motivational climate. Efforts to address public health concerns about physical inactivity require a comprehensive approach including quality physical education. It is critical that kinesiology professionals emerge as leaders in these efforts to place physical education programs at the center of promoting children's physical activity. PMID- 26558640 TI - Design, synthesis, and evaluation of guanylhydrazones as potential inhibitors or reactivators of acetylcholinesterase. AB - Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman's test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1 methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4 dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease. PMID- 26558641 TI - Two new acetylenic compounds from Asparagus officinalis. AB - Two new acetylenic compounds, asparoffins A (1) and B (2), together with two known compounds, nyasol (3) and 3"-methoxynyasol (4), were isolated from stems of Asparagus officinalis. The structures of two new compounds were elucidated on the basis of detailed spectroscopic analyses (UV, IR, MS, 1D, and 2D NMR). All compounds were evaluated for their cytotoxicities against three human cancer cell lines. PMID- 26558642 TI - Steroids for symptom control in infectious mononucleosis. AB - BACKGROUND: Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use. OBJECTIVES: The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis. SEARCH METHODS: For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE. SELECTION CRITERIA: RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite. AUTHORS' CONCLUSIONS: There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications. PMID- 26558643 TI - How to run a multiple sclerosis relapse clinic. PMID- 26558644 TI - Probiotic potentials of cereal-based beverages. AB - Probiotics offer remarkable potential for the prevention and management of various infective and noninfective disorders. They are reported to play key roles in the suppression of gastrointestinal infections, antimicrobial activity, improvement in lactose metabolism, reduction in serum cholesterol, immune system stimulation, antimutagenic properties, anticarcinogenic properties, anti diarrheal properties, and improvement in inflammatory bowel disease. Although probiotic foods are classically confined to beverages and cheese, containing live organisms of the lactic acid bacteria family, such health-promoting foods are traditionally dairy-based, comprising milk and its fermented products. However, recent research focuses on the probiotic potentials of fermented cereal-based beverages which are especially consumed in developing countries characterized by low nutritional security and high incidence of gut pathogen infections. Moreover, lactose intolerance and cholesterol content associated with dairy products, coupled with the vegetarian tendencies of diverse populations in the third world, tend to enforce the recent recourse to nondairy beverages. Probiotic microorganisms are mostly of human or animal origin; however, strains recognized as probiotics are also found in nondairy fermented substrates. This review examines the potentials of some traditional cereal-based beverages to serve as probiotic foods, their microbial and functional properties, as well as their process optimization and storage for enhanced utilization. PMID- 26558645 TI - UKMLA: American dream or nightmare? PMID- 26558646 TI - Challenges in the development of novel therapeutic strategies for treatment of endometriosis. AB - INTRODUCTION: Endometriosis is an estrogen-dependent disease that results in pelvic pain and infertility. Its treatment is often frustrating due to limited medical treatment options, complex surgical treatment and high recurrence rates. Despite the advances in our understanding of the pathogenesis over the last decades and the consequent novel therapeutic strategies, no new drugs have been introduced in daily clinical practice. AREAS COVERED: In the first part we present an overview of the pathogenesis of endometriosis. In the second part we discuss how new insights have led to the development of novel nonhormonal strategies for the treatment of endometriosis, focusing on anti-inflammatory and anti-angiogenic agents. In the third part we describe the problems encountered in the translation from experimental drugs to routine medicine for the treatment of endometriosis. EXPERT OPINION: Despite the multitude of agents that have been tested in preclinical trials, only few drugs have passed to the stage of clinical testing and none have been introduced into clinical practice. It is our opinion that the major challenges in the translation from novel agents for endometriosis is due to the use of inadequate rodent models and a lack of standardization in the design and reporting of preclinical endometriosis models. PMID- 26558648 TI - A National Assessment on Patient Safety Curricula in Undergraduate Medical Education: Results From the 2012 Clerkship Directors in Internal Medicine Survey. AB - OBJECTIVES: Patient safety is a cornerstone of quality patient care, and educating medical students about patient safety is of growing importance. This investigation was a follow-up to a 2006 study to assess the current status of patient safety curricula within undergraduate medical education in North America with the additional goals of identifying areas for improvement and barriers to implementation. METHODS: Thirteen items regarding patient safety were part of the 2012 Clerkship Directors in Internal Medicine annual survey. Questions addressed curriculum content, delivery, and barriers to implementation. RESULTS: Ninety nine clerkship directors (82%) responded. Forty-one (45.6%) reported that their medical school had a patient safety curriculum taught during medical school as compared with 25% in a 2006 survey. Fifteen (20%) reported satisfaction with students' level of safety competency at the end of the clerkship. Barriers to implementation included lack of faculty time (n = 57, 78.1%), lack of trained faculty (n = 47, 65.3%), and lack of a mandate from school's dean's office (n = 27, 38.0%). CONCLUSIONS: Our study found that less than half of North American medical schools have a formal patient safety curriculum; although this is higher than in 2006, it still exemplifies a major gap in undergraduate medical education. PMID- 26558649 TI - Standardized Consent: The Effect of Information Sheets on Information Retention. AB - INTRODUCTION: Informed consent embodies the ethical principle of autonomy of the surgical patient. Effective communication is essential to this decision-making process. Variability in consent can lead to confusion among patients and can expose the surgeon to risk in an increasingly litigious environment. OBJECTIVES: This study aimed to evaluate the use of a standardized consenting process and assess the pattern of information recall following provision of patient information sheets. METHODS: One hundred orthopedic clinic patients were randomly selected to participate in this prospective audit. Mean age was 41 years. Each participant was consented to undergo wrist manipulation under anaesthesia and K wiring using a standardized British Orthopaedic Association consent form. A 22 item questionnaire was completed based on the information provided. Half of the cohort received additional printed take-home material. Each questionnaire was repeated 1 day later to determine which aspects of consent were best retained. RESULTS: Baseline scores were low on initial questioning for each section. There was a significant decrease in information retained over 24-hour interval (mean, 8.94 versus 7.98, P <= 0.000). Where standardized forms were provided, individual baseline scores rose significantly 24 hours after initial questioning. In particular, arthritis, neurovascular injury, and infection were more likely to be remembered with provision of written information (P = 0.01). Significantly lower scores were seen in those who had not received written information (mean, 9.542 versus 6.449; P <= 0.00). CONCLUSIONS: Consent remains challenging even with a standardized process. Information retention improves significantly with the use of information sheets. We advocate the use of standard consent and provision of patient information sheets for commonly performed procedures. PMID- 26558647 TI - The role of adjuvant therapy in uterine leiomyosarcoma. AB - Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. Here we summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years. PMID- 26558650 TI - Use of Designated Nurse PICC Teams and CLABSI Prevention Practices Among U.S. Hospitals: A Survey-Based Study. AB - OBJECTIVES: The use of peripherally inserted central catheters (PICCs) has increased substantially within hospitals during the past several years. Yet, the prevalence and practices of designated nurse PICC teams (i.e., specially trained nurses who are responsible for PICC insertions at a hospital) are unknown. We, therefore, identified the prevalence of and factors associated with having a designated nurse PICC team among U.S. acute care hospitals. METHODS: We conducted a survey of infection preventionists at a random sample of U.S. hospitals in May 2013, which asked about personnel who insert PICCs and the use of practices to prevent device-associated infections, including central line-associated bloodstream infection. We compared practice use between hospitals that have a designated nurse PICC team versus those that do not. RESULTS: Survey response rate was 70% (403/575). According to the respondents, nurse PICC teams inserted PICCs in more than 60% of U.S. hospitals in 2013. Moreover, certain practices to prevent central line-associated bloodstream infection, including maximum sterile barrier precautions (93% versus 88%, P = 0.06), chlorhexidine gluconate for insertion site antisepsis (96% versus 87%, P = .003) and facility-wide insertion checklists (95% versus 87%, P = 0.02) were regularly used by a higher percentage of hospitals with nurse PICC teams compared with those without. CONCLUSIONS: These data suggest that nurse PICC teams play an integral role in PICC use at many hospitals and that use of such teams may promote key practices to prevent complications. Better understanding of the role, composition, and practice of such teams is an important area for future study. PMID- 26558651 TI - Analysis of a Standardized Perioperative Pain Management Order Set in Highly Opioid-Tolerant Patients. AB - OBJECTIVE: The aim was to assess a standardized order set for perioperative pain management in highly opioid-tolerant patients undergoing elective orthopedic surgery. METHODS: This retrospective chart review evaluated a pain order set in highly opioid-tolerant patients undergoing elective total knee or total hip arthroplasty from January 2010 through August 2012. Based on the date of the surgery, patients were allocated into preimplementation or postimplementation order set groups. The primary outcome assessed whether an adjustment in daily opioid dosage was required within the first 48 hours postoperatively. Secondary outcomes included pain scores, length of hospitalization, and safety outcomes. RESULTS: Sixty patients were included in the analysis. An adjustment to postoperative opioid therapy occurred in 62% of the patients in the preimplementation group and in 56% of postimplementation group patients (P = 0.786). There were no differences in median pain scores 48 hours postoperatively (P = 0.348). Cumulative toxicity was increased after order set implementation compared with previous patients (44% versus 5%, P < 0.005); however, opioid doses held for sedation was the only individual toxicity to reach statistical significance (P = 0.011). CONCLUSIONS: This study is the first to evaluate a standardized order set for pain management in highly opioid-tolerant patients undergoing elective orthopedic surgery. The order set demonstrated similar efficacy to previous treatment modalities, but opioid-induced sedation was of concern with the order set. After the initial analysis, the order set was modified to minimize opioid-induced sedation. Continual safety analysis is warranted for quality improvement to enhance perioperative pain management in highly opioid-tolerant patients. PMID- 26558652 TI - Electronic Health Record-Related Events in Medical Malpractice Claims. AB - BACKGROUND: There is widespread agreement that the full potential of health information technology (health IT) has not yet been realized and of particular concern are the examples of unintended consequences of health IT that detract from the safety of health care or from the use of health IT itself. The goal of this project was to obtain additional information on these health IT-related problems, using a mixed methods (qualitative and quantitative) analysis of electronic health record-related harm in cases submitted to a large database of malpractice suits and claims. METHODS: Cases submitted to the CRICO claims database and coded during 2012 and 2013 were analyzed. A total of 248 cases (<1%) involving health IT were identified and coded using a proprietary taxonomy that identifies user- and system-related sociotechnical factors. Ambulatory care accounted for most of the cases (146 cases). Cases were most typically filed as a result of an error involving medications (31%), diagnosis (28%), or a complication of treatment (31%). More than 80% of cases involved moderate or severe harm, although lethal cases were less likely in cases from ambulatory settings. Etiologic factors spanned all of the sociotechnical dimensions, and many recurring patterns of error were identified. CONCLUSIONS: Adverse events associated with health IT vulnerabilities can cause extensive harm and are encountered across the continuum of health care settings and sociotechnical factors. The recurring patterns provide valuable lessons that both practicing clinicians and health IT developers could use to reduce the risk of harm in the future. The likelihood of harm seems to relate more to a patient's particular situation than to any one class of error.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share thework provided it is properly cited. The work cannot be changed in any way or used commercially. PMID- 26558653 TI - Acute Invasive Fungal Rhinosinusitis in Children With Hematologic Malignancies: Outcome of Surgical Treatment. AB - The incidence of acute invasive fungal rhinosinusitis (AIFR) is rising due to more aggressive chemotherapy and longer survival of immunosuppressed patients. Early diagnosis and appropriate but nonmutilating surgical treatment are particularly problematic in the pediatric population. This study aimed to evaluate the outcome of surgery for pediatric AIFR. Medical records of children surgically treated for AIFR between 1998 and 2014 were reviewed. Diagnosis was based on both histopathological and microbiological confirmation. Surgery was performed with curative intent and repeated for any resectable extension. The children underwent endoscopy and magnetic resonance imaging every 2 and 6 months, respectively, during the first postoperative year. Thirteen patients (2-18 years old) met the EORTC/MSG criteria for proven invasive fungal sinusitis; fungal invasion was diagnosed by preoperative biopsy and confirmed in the surgical specimen. All patients underwent an average of two endoscopic procedures (range 1 3), and four of them also underwent an open surgery. The local control rate was at least 79%. There was no facial disfiguration during follow-up (average 41 months). Although AIFR is still associated with high mortality, aggressive medical and surgical treatment provides local control in most cases. Fair outcome should encourage a maximal joint effort of pediatric hemato-oncologists and otorhinolaryngologists in the management of AIFR. PMID- 26558654 TI - From AIDS to TB vaccines--A career in infectious diseases and translational vaccinology. PMID- 26558655 TI - A water-soluble metal-organic complex array as a multinuclear heterometallic peptide amphiphile that shows unconventional anion dependency in its self assembly. AB - Water-soluble metal-organic complex array 1, bearing Ru(II), Pt(II) and Rh(III) complexes at the side residues of the short peptide, exhibits anion and pH responsive self-assembly behaviours in aqueous media. NaCl-induced aggregation of 1 at neutral pH was suppressed in phosphate buffered saline containing a mixture of Cl(-), HPO4(2-) and H2PO4(-), which is unconventional for a peptide amphiphile. PMID- 26558656 TI - Proteomic landscape in Central and Eastern Europe: the 9th Central and Eastern European Proteomic Conference, Poznan, Poland. AB - Every year since 2007, the Central and Eastern European Proteomic Conference (CEEPC) has excelled in representing state-of-the-art proteomics in and around Central and Eastern Europe, and linking it to international institutions worldwide. Its mission remains to contribute to all approaches of proteomics including traditional and often-revisited methodologies as well as the latest technological achievements in clinical, quantitative and structural proteomics with a view to systems biology of a variety of processes. The 9th CEEPC was held from June 15th to 18th, 2015, at the Institute of Bioorganic Chemistry, Polish Academy of Sciences in Poznan, Poland. The scientific program stimulated exchange of proteomic knowledge whilst the spectacular venue of the conference allowed participants to enjoy the cobblestoned historical city of Poznan. PMID- 26558657 TI - Foreword. PMID- 26558658 TI - Osteosarcoma of the Foot. AB - A 40-year-old man presented with a large and painful right foot mass. The patient reported a history of a recurrent right foot mass treated elsewhere with 3 prior surgical excisions. PMID- 26558659 TI - Team Physicians Must Advocate for Lifelong Musculoskeletal Well-being. PMID- 26558660 TI - Amputated Lower Limb Fixation to the Fracture Table. AB - Fractures of the proximal and diaphyseal femur are frequently internally fixed using a fracture table with fracture reduction obtained by traction and adequate rotation exerted on the slightly abducted extremity. Although rare, these fractures may occur on an amputated limb. If so, standard use of a fracture table is not possible. To address this situation, the authors describe a simple novel technique allowing rigid fixation of the amputated limb to the traction device of the fracture table that provides accurate control of reduction in all planes. PMID- 26558661 TI - Three-Dimensional Printing in Orthopedic Surgery. AB - Three-dimensional (3D) printing is emerging as a clinically promising technology for rapid prototyping of surgically implantable products. With this commercially available technology, computed tomography or magnetic resonance images can be used to create graspable objects from 3D reconstructed images. Models can enhance patients' understanding of their pathology and surgeon preoperative planning. Customized implants and casts can be made to match an individual's anatomy. This review outlines 3D printing, its current applications in orthopedics, and promising future directions. PMID- 26558662 TI - Current Rehabilitation Concepts for Anterior Cruciate Ligament Surgery in Athletes. AB - The anterior cruciate ligament is the most commonly disrupted ligament in the knee in high-performance athletes. Most recently, advancements in surgical technique and graft fixation have enabled athletes to participate in early postoperative rehabilitation, focusing on range of motion and progressing to patellar mobilization, strengthening, and neuromuscular control. Several rehabilitation protocols exist with variations in specific exercises, progression through phases, and key components. The ultimate goal of rehabilitation is to return the athlete to preinjury performance level, including motion and strength, without injuring or elongating the graft. Each athlete is unique; thus, safe return to play should be individualized rather than follow a particular postoperative month or time line. This article provides an overview of the application and the scientific basis for formulating a rehabilitation protocol prior to and following anterior cruciate ligament surgery. PMID- 26558663 TI - Unipolar Versus Bipolar Hemiarthroplasty for Displaced Femoral Neck Fractures in Elderly Patients. AB - Hip replacement using hemiarthroplasty (HA) is a common surgical procedure in elderly patients with femoral neck fractures. However, questions remain regarding the choice of unipolar or bipolar HA. A meta-analysis of randomized, controlled trials (RCTs) was performed to determine whether bipolar HA was associated with lower rates of dislocation, reoperation, acetabular erosion, mortality, and general complications, as well as lower Harris Hip Scores, compared with unipolar HA. The authors searched PubMed and the Cochrane Register of Controlled Trials database, and 8 RCTs (including a total of 1100 patients) were selected for meta analysis. Risk ratios (RRs) and weighted mean differences (WMDs) from each trial were pooled using random-effects or fixed-effects models depending on the heterogeneity of the included studies. There were no differences in dislocation (RR=1.20; 95% confidence interval [CI], 0.47 to 3.07), reoperation (RR=0.64; 95% CI, 0.33 to 1.26), acetabular erosion (RR=2.29; 95% CI, 0.85 to 6.12), mortality (RR=0.85; 95% CI, 0.63 to 1.13), and general complications (RR=1.05; 95% CI, 0.70 to 1.56). The authors found no difference in postoperative Harris Hip Scores between patients undergoing unipolar vs bipolar HA (WMD=-1.32; 95% CI, -3.29 to 0.65; P=.19). Unipolar and bipolar HA achieved similar clinical outcomes in patients with displaced femoral neck fractures. PMID- 26558664 TI - Long-term Results After Ankle Syndesmosis Injuries. AB - Syndesmotic disruption occurs in more than 10% of ankle fractures. Operative treatment with syndesmosis screw fixation has been successfully performed for decades and is considered the gold standard of treatment. Few studies have reported the long-term outcomes of syndesmosis injuries. This study investigated long-term patient-reported, radiographic, and functional outcomes of syndesmosis injuries treated with screw fixation and subsequent timed screw removal. A retrospective cohort study was carried out at a Level I trauma center. The study group included 43 patients who were treated for ankle fractures with associated syndesmotic disruptions between December 2001 and May 2011. The study included case file reviews, self-reported questionnaires, radiologic reviews, and clinical assessments. At 5.1 (+/-1.76) years after injury, 60% of participants had pain, 26% had degenerative changes, 51% had loss of tibiofibular overlap, and 33% showed medial clear space widening. Retained syndesmotic positions on radiographs were linked to better self-reported outcomes. There is an inversely proportional relation between age at the time of injury and satisfaction with the outcome of the ankle fracture as well as a directly proportional relation between age at the time of injury and pain compared with the preinjury state. Optimal restoration and preservation of the syndesmosis is crucial. Syndesmotic disruption is associated with poor long-term outcomes after ankle fracture. Greater age is a risk factor for chronic pain and dissatisfaction with the outcome of ankle fracture and syndesmosis injury. Therefore, patient education to facilitate realistic expectations about recovery is vital, especially in older patients. PMID- 26558665 TI - Blood Loss and Transfusion After Topical Tranexamic Acid Administration in Primary Total Knee Arthroplasty. AB - There has been much debate and controversy about the safety and efficacy of the topical use of tranexamic acid in primary total knee arthroplasty (TKA). The purpose of this study was to perform a meta-analysis to evaluate whether there is less blood loss and lower rates of transfusion after topical tranexamic acid administration in primary TKA. A systematic review of the electronic databases PubMed, CENTRAL, Web of Science, and Embase was undertaken. All randomized, controlled trials and prospective cohort studies evaluating the effectiveness of topical tranexamic acid during primary TKA were included. The focus of the analysis was on the outcomes of blood loss results, transfusion rate, and thromboembolic complications. Subgroup analysis was performed when possible. Of 387 studies identified, 16 comprising 1421 patients (1481 knees) were eligible for data extraction and meta-analysis. This study indicated that when compared with the control group, topical application of tranexamic acid significantly reduced total drain output (mean difference, -227.20; 95% confidence interval, 347.11 to -107.30; P<.00001), total blood loss (mean difference, -311.28; 95% confidence interval, -404.94 to -217.62; P<.00001), maximum postoperative hemoglobin decrease (mean difference, -0.73; 95% confidence interval, -0.96 to 0.50; P<.00001), and blood transfusion requirements (risk ratios, 0.33; 95% confidence interval, 0.24 to 0.43; P=.14). The authors found a statistically significant reduction in blood loss and transfusion rates when using topical tranexamic acid in primary TKA. Furthermore, the currently available evidence does not support an increased risk of deep venous thrombosis or pulmonary embolism due to tranexamic acid administration. Topical tranexamic acid was effective for reducing postoperative blood loss and transfusion requirements without increasing the prevalence of thromboembolic complications. PMID- 26558666 TI - Evolving Role of Ultrasound in Therapeutic Injections of the Upper Extremity. AB - Ultrasound machines are creating more refined pictures and becoming more user friendly and readily accessible. As a result, ultrasound is being increasingly used for therapeutic purposes. One example involves the use of ultrasound guidance in musculoskeletal interventional procedures, such as joint injections, tendon sheath injections, and peripheral nerve blocks. Technical considerations and therapeutic results have been described for multiple locations about the upper extremities, with varying levels of success. The implementation of ultrasound-guided injections in the orthopedist's clinic has therapeutic, financial, and provider role implications. Given these potential benefits, orthopedic providers, both in practice and residency, would benefit from increased exposure and education in ultrasound use. Ultrasound provides the benefit of real-time, dynamic imaging without the radiation exposure of fluoroscopy, and ultrasound-guided injections can be performed in the office, as opposed to the operating room, which is frequently required when using fluoroscopy. A basic knowledge of the principles and terms used in ultrasound is required. With these simple principles, a practitioner can review techniques for specific areas of the musculoskeletal system and begin using ultrasound to guide injections. Many locations for diagnostic and/or therapeutic injections in the upper extremities have improved accuracy and benefit with the use of ultrasound vs blind techniques, although a few have not been shown to have a significant difference in the literature. The educational and professional implications can be significant, but these potential benefits need to be carefully weighed against costs by each orthopedic practice. PMID- 26558667 TI - Acute Management of Open Fractures: An Evidence-Based Review. AB - Open fractures are complex injuries associated with high morbidity and mortality. Despite advances made in fracture care and infection prevention, open fractures remain a therapeutic challenge with varying levels of evidence to support some of the most commonly used practices. Additionally, a significant number of studies on this topic have focused on open tibial fractures. A systematic approach to evaluation and management should begin as soon as immediate life-threatening conditions have been stabilized. The Gustilo classification is arguably the most widely used method for characterizing open fractures. A first-generation cephalosporin should be administered as soon as possible. The optimal duration of antibiotics has not been well defined, but they should be continued for 24 hours. There is inconclusive evidence to support either extending the duration or broadening the antibiotic prophylaxis for type Gustilo type III wounds. Urgent surgical irrigation and debridement remains the mainstay of infection eradication, although questions persist regarding the optimal irrigation solution, volume, and delivery pressure. Wound sampling has a poor predictive value in determining subsequent infections. Early wound closure is recommended to minimize the risk of infection and cannot be substituted by negative-pressure wound therapy. Antibiotic-impregnated devices can be important adjuncts to systemic antibiotics in highly contaminated or comminuted injuries. Multiple fixation techniques are available, each having advantages and disadvantages. It is extremely important to maintain a high index of suspicion for compartment syndrome, especially in the setting of high-energy trauma. PMID- 26558668 TI - Residual Hole Orientation After Plate Removal: Effect on the Clavicle. AB - Clavicle fractures account for 2.6% to 4% of all fractures. Surgical stabilization of this type of injury is becoming more common. Anterior inferior plating and superior plating are 2 popular approaches to open reduction and internal fixation. Reports of plate removal have raised concerns about reinjury. The goal of the current study was to determine whether the orientation of screw holes in clavicles after removal of an anterior inferior plate vs a superior plate have different biomechanical effects on stiffness and load to failure. The medial and lateral ends of 28 matched pairs of fresh clavicles were potted. Pilot holes, 2.5 mm in diameter, were drilled and oriented anterior inferiorly or superiorly, simulating those left after removal of a plate for a middle-third fracture. The clavicles underwent dynamic axial compression and 3-point load to failure, replicating forces associated with reinjury. Clavicles with anterior inferior holes had a statistically significant higher median maximal load difference of 139 N compared with those with superior holes (P=.013). Anterior inferior holes showed a statistically significant median increase in stiffness of 16.3 N/mm compared with superior holes (P=.036). Clavicles with anterior inferior holes had a statistically significant increase in median maximal load to failure and an increase in median stiffness compared with those with superior holes. This finding is relevant for patients who undergo hardware removal and return to activities that put them at risk for repeat high-impact injuries to the clavicle. PMID- 26558669 TI - Relationship Between Wrist Motion and Capitolunate Reduction in Four-Corner Arthrodesis. AB - The authors retrospectively studied 36 patients with degenerative changes associated with scaphoid nonunion and scapholunate advanced collapse treated with circular plate fixation and bone graft. The goals of the study were to review the incidence of dorsal impingement, nonunion of arthrodesis, loose hardware, broken screws, and limitation in wrist motion associated with correct or incorrect surgical capitolunate reduction. Surgical indications were scapholunate advanced collapse (3 patients), scaphoid nonunion advanced collapse (32 patients), and sequelae of irreducible perilunate dislocation (1 patient). All of the patients were men, with a mean age of 48 years (range, 35-68 years). Average follow-up was 56 months (range, 12-108 months). Functional outcomes evaluated were pain with the visual analog scale, range of motion, grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score, satisfaction, and time to union. Mean visual analog scale score was 7 (range, 5-9) preoperatively and 1 (range, 0-2) postoperatively. Average wrist range of motion was 42 degrees in extension, 36 degrees in flexion, 15 degrees in ulnar deviation, and 12 degrees in radial deviation. Mean grip strength was 34 kg preoperatively, 50 kg postoperatively, and 56 kg contralaterally. Thirty-five of the 36 patients achieved union at 6 months. Degenerative changes at the radiolunate articulation were present in 1 patient 62 months after surgery, but he was asymptomatic. Mean capitolunate angle was 38o preoperatively and 9o postoperatively. Poor correlation was found between the measured capitate-lunate angle and subsequent flexion and extension (r=0.32 and r=0.17, respectively) using the Pearson correlation coefficient. The authors noted 1 or 2 broken screws in 3 cases (8.3%) and hardware dorsal impingement in the plate in 6 cases (16.6%). Mean DASH score was 24 of 100. Overall patient satisfaction was 70%. PMID- 26558670 TI - Percutaneous Ultrasound-Guided Hydrodissection of a Symptomatic Sural Neuroma. AB - Symptomatic neuromas of the sural nerve are a rare but significant cause of pain and debilitation in athletes. Presentation is usually in the form of chronic pain and dysesthesias or paresthesias of the lateral foot and ankle. Treatment traditionally ranges from conservative measures, such as removing all external compressive forces, to administration of nonsteroidal anti-inflammatory drugs, vitamin B6, tricyclic antidepressants, antiepileptics, or topical anesthetics. This article reports a case of sural nerve entrapment in a 34-year-old male triathlete with a history of recurrent training-induced right-sided gastrocnemius strains. The patient presented with numbness in the right lateral foot and ankle that had persisted for 3 months, after he was treated unsuccessfully with extensive nonoperative measures, including anti-inflammatory drugs, activity modification, and a dedicated physical therapy program of stretching and strengthening. Orthopedic assessment showed worsening pain with forced passive dorsiflexion and manual pressure applied over the distal aspect of the gastrocnemius. Plain radiographs showed normal findings, but in-office ultrasound imaging showed evidence of sural nerve entrapment with edema and neuromatous scar formation in the absence of gastrocnemius or soleus pathology. Percutaneous ultrasound-guided hydrodissection of the sural nerve at the area of symptomatic neuroma and neural edema was performed the same day. The patient had complete relief of symptoms and full return to the preinjury level of participation in competitive sports. This case report shows that hydrodissection, when performed by an experienced physician, can be an effective, minimally invasive technique for neurolysis in the setting of sural nerve entrapment, resulting in improvement in clinical symptoms. PMID- 26558671 TI - Spontaneous Bilateral Femoral Fractures After High-Dose Zoledronic Acid. AB - The authors report a case of spontaneous bilateral diaphyseal femoral fractures believed to be caused by oversuppression of bone remodeling as a result of long term, high-dose treatment with bisphosphonate. The patient reported pain in both thighs before the fractures. Typical pathologic changes appeared on both femoral radiograph and bone scan before the fractures. Several hours after admission to the emergency department of the authors' institution, the patient underwent closed reduction and internal fixation with intramedullary nails for the bilateral femoral diaphyseal fractures. Treatment with zoledronic acid was immediately discontinued. In recent years, low-energy femoral diaphyseal fractures in patients undergoing long-term bisphosphonate treatment have been reported. It is believed that the prolonged treatment causes long-term suppression of bone remodeling and accumulation of microdamage. It is important to observe patients who are undergoing bisphosphonate treatment carefully. In this case study, the authors report the patient's unique medical history. PMID- 26558672 TI - Iliopsoas Bursa-Hip Capsule Connection Leading to Intra-abdominal Fluid Extravasation. AB - Intra-abdominal fluid extravasation is a rare complication of hip arthroscopy, with a reported incidence of 0.16%. Associated risk factors include recent acetabular fracture, extra-articular procedures, iliopsoas tenotomy, and high fluid pump pressure. These previously reported risk factors were not present in the 48-year-old woman reported in this article. The patient elected to undergo hip arthroscopy for mechanical hip pain that persisted for 18 months. Preoperative magnetic resonance imaging scan showed a "normal variant communication [between] the iliopsoas bursa" and the hip capsule. Postoperative examination showed a tense, distended abdomen. After extubation, the patient had severe abdominal and pleuritic chest pain. Postoperative imaging showed significant retro- and intraperitoneal fluid extravasation. Ultrasound-guided paracentesis was used to drain the intraperitoneal fluid collection, with a significant decrease in pain. The patient returned home less than 24 hours later, with no further complications. The authors believe that the preexisting connection between the hip capsule and the iliopsoas bursa allowed the arthroscopy fluid to easily track proximally within the tendon sheath, despite relatively low fluid pump pressure. Surgeons should be aware of this possible "normal variant communication," which may be considered a relative contraindication to hip arthroscopy, especially in patients with arthritic changes on preoperative imaging. This must be addressed with the patient preoperatively, with proper counseling and patient selection. If arthroscopy is pursued, the surgical and anesthesia teams must be vigilant for signs of intra abdominal fluid extravasation and must be prepared to treat this potentially serious complication. PMID- 26558673 TI - Lumbar Diskography and Failed Back Syndrome in Patients Receiving Workers' Compensation. AB - Lumbar diskography (LD) is frequently used in the evaluation of patients with degenerative disk disease and diskogenic low back pain. Its safety and diagnostic accuracy are a topic of debate. No study has evaluated the efficacy of LD within the clinically distinct workers' compensation population. Within this setting, the authors wished to determine the effect of undergoing LD before diskogenic fusion on rates of postoperative failed back surgery syndrome (FBSS). Also, the authors compared opioid analgesic use between patients undergoing LD and patients not undergoing LD. ICD-9 diagnoses and CPT procedural codes were used to identify 1591 patients from the Ohio Bureau of Workers' Compensation who underwent diskogenic fusion between 1993 and 2013. A total of 682 patients underwent LD before fusion, which formed the LD group, with the remaining 909 patients as controls. The authors used a multivariate logistic regression analysis while correcting for relevant covariates. Diskography before fusion was a positive predictor of postoperative FBSS (P=.04; odds ratio, 1.44). The rate of FBSS was 13.9% of the LD group and 8.8% in the control group. Postoperatively, the LD group was supplied with a significantly higher daily opioid analgesic load (P=.04) for an average of 130 additional days (P<.01). Additional predictors of FBSS included the ability to remain at work within 1 week of index fusion (P=.02; odds ratio, 0.54), male sex (P=.03; odds ratio, 1.51), preoperative narcotic use for more than 1 year (P=.02; odds ratio, 1.53), and fusion technique (P=.03). Diskography should ideally help identify good candidates for lumbar fusion. However, the authors' study raises significant concerns regarding LD's current role within the workers' compensation population. PMID- 26558674 TI - Gait Analysis Using a Support Vector Machine for Lumbar Spinal Stenosis. AB - Lumbar spinal canal stenosis (LSS) is diagnosed based on physical examination and radiological documentation of lumbar spinal canal narrowing. Differential diagnosis of the level of lumbar radiculopathy is difficult in multilevel spinal stenosis. Therefore, the authors focused on gait analysis as a classification method to improve diagnostic accuracy. The goal of this study was to identify gait characteristics of L4 and L5 radiculopathy in patients with LSS and to classify L4 and L5 radiculopathy using a support vector machine (SVM). The study group comprised 13 healthy volunteers (control group), 11 patients with L4 radiculopathy (L4 group), and 22 patients with L5 radiculopathy (L5 group). Light emitting diode markers were attached at 5 sites on the affected side, and walking motion was analyzed using video recordings and the authors' development program. Potential gait characteristics of each group were identified to use as SVM parameters. In the knee joint of the L4 group, the waveform was similar to that of normal gait, but knee extension at initial contact was slightly greater than that of the other groups. In the ankle joint of the L5 group, the one-peak waveform pattern with disappearance of the second peak was present in 10 (45.5%) of 22 cases. The total classification accuracy was 80.4% using the SVM. The highest and lowest classification accuracies were obtained in the control group (84.6%) and the L4 group (72.7%), respectively. The authors' walking motion analysis system identified several useful factors for differentiating between healthy individuals and patients with L4 and L5 radiculopathy, with a high accuracy rate. PMID- 26558675 TI - The Effect of Cartilage Injury After Arthroscopic Stabilization for Shoulder Instability. AB - This study was undertaken to (1) determine the incidence of articular cartilage injuries in patients with instability of the glenohumeral joint, (2) determine whether recurrent dislocations increased the risk of articular damage, and (3) correlate these injuries with postoperative clinical outcomes. A cohort was identified of consecutive patients who underwent diagnostic magnetic resonance imaging and shoulder arthroscopy for glenohumeral instability with documented dislocation or subluxation between 1997 and 2006 at a single institution. Patients with moderate or severe osteoarthritis were excluded. Arthroscopic findings were recorded, including lesion location and Outerbridge grade. The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) was used to assess outcome in 61 patients who were available for follow-up. Outcomes were compared between shoulders with and without articular lesions. A total of 87 shoulders (83 patients) met the inclusion criteria, with 69 (83%) men and 14 (17%) women. Mean age was 26.1 years (range, 18-64 years), and mean follow up was 36 months (range, 33-39 months). Cartilage injuries were found in 56 shoulders (64%). Previously documented shoulder dislocation requiring closed reduction (P=.046) and the number of discrete dislocations (P=.032) were significant for glenoid injury. A greater number of dislocations was associated with higher-grade lesions of the glenohumeral joint (P<.001). Overall, mean ASES score was 89.6 (range, 37-100). In patients with an articular cartilage lesion, mean ASES score was 90.4 (range, 58-100) compared with 88.1 (range, 37-100) in those without this injury (P=.75). Although clinical outcomes were not significantly affected, further investigation is warranted to establish a relationship between these injuries and longer-term outcomes. PMID- 26558676 TI - Intraoperative Fluoroscopy Improves Component Position During Anterior Hip Arthroplasty. AB - The goal of this retrospective review was to determine whether fluoroscopic guidance improves acetabular cup abduction and anteversion alignment during anterior total hip arthroplasty. The authors retrospectively reviewed 199 patients (fluoroscopy group, 98; nonfluoroscopy group, 101) who underwent anterior total hip arthroplasty at a single center with and without C-arm fluoroscopy guidance. Included in the study were patients of any age who underwent primary anterior approach total hip arthroplasty performed by a single surgeon, with 6-month postoperative anteroposterior pelvis radiographs. Acetabular cup abduction and anteversion angles were measured and compared between groups. Mean acetabular cup abduction and anteversion angles were 43.4 degrees (range, 26.0 degrees -57.4 degrees ) and 23.1 degrees (range, 17 degrees -28 degrees ), respectively, in the fluoroscopy group. Mean abduction and anteversion angles were 45.9 degrees (range, 29.7 degrees -61.3 degrees ) and 23.1 degrees (range, 17 degrees -28 degrees ), respectively, after anterior total hip arthroplasty without the use of C-arm guidance (nonfluoroscopy group). The use of fluoroscopy was associated with a statistically significant difference in cup abduction (P=.002) but no statistically significant difference in anteversion angles. In the fluoroscopy group, 80% of implants were within the combined safe zone compared with 63% in the nonfluoroscopy group. A significantly higher percentage of both acetabular cup abduction angles and combined anteversion and abduction angles were in the safe zone in the fluoroscopy group. Fluoroscopy is not required for proper anteversion placement of acetabular components, but it may increase ideal safe zone placement of components. PMID- 26558677 TI - Percutaneous Screw Fixation of Crescent Fracture-Dislocation of the Sacroiliac Joint. AB - Crescent fracture-dislocation of the sacroiliac joint (CFDSIJ) is a type of lateral compression pelvic injury associated with instability. Open reduction and internal fixation is a traditional treatment of CFDSIJ. However, a minimally invasive method has never been reported. The purpose of this study was to assess the outcome of closed reduction and percutaneous fixation for different types of CFDSIJ and present their clinical outcome. The authors reviewed 117 patients diagnosed with CFDSIJ between July 2003 and July 2013. Closed reduction and percutaneous fixation was performed in 73 patients. Treatment selection was based on Day's fracture classification. For type I fractures, fixation perpendicular to the fracture line were performed. For type II fractures, crossed fixation was performed. For type III fractures, fixation was performed with iliosacral screws. Forty-four patients were treated by open reduction and plate fixation. Demographics, fracture pattern distribution, blood loss, incision lengths, revision surgeries, radiological results, and functional scores were compared. All 117 patients were followed for more than 6 months (mean, 14 months [range, 6 24 months]). Blood loss, extensive exposure, duration of posterior ring surgery, duration of hospital stay, and infection rates were lower in the closed group (P<.01). Patients in the closed group achieved better functional performance (P<.01). There were no significant differences in reduction quality (P=.32), revision surgery rates (P=.27), and iatrogenic neurologic injuries (P=.2) between the 2 groups. The authors' results indicate that closed reduction and percutaneous fixation is a safe and effective surgical method for CFDSIJ. PMID- 26558678 TI - Open Reduction of Pediatric Femoral Neck Fractures Reduces Osteonecrosis Risk. AB - Pediatric femoral neck fractures are rare injuries that are associated with a high risk of osteonecrosis of the femoral head. This study compared pediatric patients with fully displaced femoral neck fractures treated with either open reduction and internal fixation (ORIF) or closed reduction and internal fixation (CRIF). After institutional review board approval was obtained, the authors identified 53 patients who were treated for femoral neck fracture between 2003 and 2012. Inclusion criteria were as follows: (1) diagnosis of a fully displaced femoral neck fracture with no anatomic cortical contact; (2) age of at least 4 years; and (3) clinical/radiographic follow-up of at least 1 year. Medical records and radiographs were retrospectively reviewed. Excluded from the study were 16 patients who had fractures that were not fully displaced, 4 who were outside of the eligible age range, 1 who had insufficient radiographs, and 10 who had insufficient follow-up. Of the 22 patients included, 6 were treated with ORIF and 16 were treated with CRIF. Treatment groups were compared with Fisher's exact test for categorical outcome data and the Wilcoxon rank-sum test for continuous variables. There was a significantly (P=.051) greater occurrence of osteonecrosis after CRIF (50%) than after ORIF (0%). Further, patients who underwent ORIF had a higher (P=.009) quality of reduction, a higher (P=.046) rate of anatomic union, and fewer (P=.009) complications than those who underwent CRIF. Major complications occurred in significantly fewer (P=.015) hips after ORIF than after CRIF. No significant difference (P=.477) was seen between groups, according to the Ratliff assessment of final results. Fully displaced pediatric femoral neck fractures treated with ORIF had a significantly higher quality of reduction, with fewer complications, including osteonecrosis, than those treated with CRIF. PMID- 26558679 TI - Door Opening Affects Operating Room Pressure During Joint Arthroplasty. AB - Many resources are expended to ensure a sterile operating room environment. Efforts are made to prevent exposure of patients to personnel and to achieve positive room pressure to keep out airborne contaminants. Foot traffic into and out of the operating room during surgery can undermine these efforts. The authors investigated the number and duration of operating room door openings during hip and knee arthroplasty procedures and the effect of the door openings on room pressure. They tested the hypothesis that door openings defeat positive pressure, permitting air flow into the room. Room pressure and door status were monitored electronically during 191 hip and knee arthroplasty procedures. Operating room staff were unaware that data were being collected. The authors evaluated the data with regression analysis to determine whether the number and duration of door openings had an effect on room pressure. Significance was set at P<.05. Doors were open, on average, 9.5 minutes per case. In 77 of 191 cases, positive pressure was defeated, allowing air flow to reverse into the operating room. Total time with the door open significantly affected the minimum pressure recorded in the room (P<.02), but did not significantly affect average room pressure (P=.7). This finding suggested that the loss of positive pressure was a transient event from which the room recovered. The number and duration of door openings showed a significant association with length of surgery. Door openings threaten positive pressure, potentially jeopardizing operating room sterility. The causes of excessive operating room traffic must be evaluated to identify ways to reduce this traffic and the associated risks. PMID- 26558680 TI - Total En Bloc Spondylectomy for Primary and Metastatic Spine Tumors. AB - This study reports the surgical and clinical outcomes of spinal tumors managed with total en bloc spondylectomy. The authors searched their prospectively maintained database for patients undergoing total en bloc spondylectomy between 2001 and 2013. Ten patients (9 men, 1 woman; average age, 50.7 years; range, 42 68 years) were identified. The authors obtained demographic information, surgical outcomes (estimated blood loss, complications), and clinical outcomes (recurrence, survival). All patients had pain and were classified as American Spinal Injury Association grade E. The lesions were located in the thoracic (8 patients) and lumbar (2 patients) spine. Anterior column reconstruction was performed with strut allograft (7 patients), mesh cage (2 patients), and polymethyl methacrylate (1 patient). An average of 2.3 (range, 2-4) of 6 portions of the vertebrae were involved, according to the Kostuik classification. Mean estimated blood loss, operative time, and hospital stay were 3.5 L, 500 minutes, and 7.8 days, respectively. Perioperative complications included pleural tear (2 patients) and aortic tear, vena cava tear, retained sponge, pulmonary embolism, urinary tract infection, pneumothorax, anterior column support failure, and prominent instrumentation requiring removal (1 patient each). Postoperatively, all patients remained classified as American Spinal Injury Association grade E. Two patients had recurrence at distant spinal segments, and 1 had a new lesion in the thigh. Five patients had died (mean, 34.5 months after surgery), and 5 were alive a mean of 19.6 months after surgery (range, 6-48 months). Total en bloc spondylectomy is challenging, but in appropriately selected patients, it can be used to treat primary and metastatic spinal lesions. PMID- 26558681 TI - MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction. AB - Heart disease remains a major complication of diabetes, and the identification of new therapeutic targets is essential. This study investigates the role of the protein kinase MK2, a p38 mitogen-activated protein kinase downstream target, in the development of diabetes-induced cardiomyopathy. Diabetes was induced in control (MK2(+/+)) and MK2-null (MK2(-/-)) mice using repeated injections of a low dose of streptozotocin (STZ). This protocol generated in MK2(+/+) mice a model of diabetes characterized by a 50% decrease in plasma insulin, hyperglycemia, and insulin resistance (IR), as well as major contractile dysfunction, which was associated with alterations in proteins involved in calcium handling. While MK2(-/-)-STZ mice remained hyperglycemic, they showed improved IR and none of the cardiac functional or molecular alterations. Further analyses highlighted marked lipid perturbations in MK2(+/+)-STZ mice, which encompass increased 1) circulating levels of free fatty acid, ketone bodies, and long-chain acylcarnitines and 2) cardiac triglyceride accumulation and ex vivo palmitate beta-oxidation. MK2(-/-)-STZ mice were also protected against all these diabetes-induced lipid alterations. Our results demonstrate the benefits of MK2 deletion on diabetes-induced cardiac molecular and lipid metabolic changes, as well as contractile dysfunction. As a result, MK2 represents a new potential therapeutic target to prevent diabetes-induced cardiac dysfunction. PMID- 26558682 TI - Coxsackievirus B5 Infection Induces Dysregulation of microRNAs Predicted to Target Known Type 1 Diabetes Risk Genes in Human Pancreatic Islets. AB - Extensive research has identified enterovirus (EV) infections as key environmental triggers of type 1 diabetes. However, the underlying molecular mechanisms via which EVs contribute to the pathogenesis of type 1 diabetes remain unclear. Given that EVs dysregulate host microRNAs (miRNAs), which function as key regulators of beta-cell biology, we investigated the impact of coxsackievirus B5 (CVB5) infection on the cellular expression of miRNAs within human islets. Using high-throughput quantitative PCR nanofluidics arrays, the expression of 754 miRNAs was examined in CVB5-infected human pancreatic islets. In total, 33 miRNAs were significantly dysregulated (>= threefold difference) in the infected compared with control islets (P < 0.05). Subsequently, these differentially expressed miRNAs were predicted to target mRNAs of 57 known type 1 diabetes risk genes that collectively mediate various biological processes, including the regulation of cell proliferation, cytokine production, the innate immune response, and apoptosis. In conclusion, we report the first global miRNA expression profiling of CVB5-infected human pancreatic islets. We propose that EVs disrupt the miRNA-directed suppression of proinflammatory factors within beta cells, thereby resulting in an exacerbated antiviral immune response that promotes beta-cell destruction and eventual type 1 diabetes. PMID- 26558683 TI - The potential of bacteriophage cocktail in eliminating Methicillin-resistant Staphylococcus aureus biofilms in terms of different extracellular matrices expressed by PIA, ciaA-D and FnBPA genes. AB - BACKGROUND: This study assessed novel approach of using highly lytic phages against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) biofilms with and without biofilm extracellular matrix- disrupting chemical. METHOD: The resultant phage-based control was assessed in relation to the type of biofilm extracellular matrix namely, polysaccharide intercellular adhesion (PIA) or proteinacious fibronectin binding protein A (FnBPA). The biofilms were formed in vitro by 24 h incubation of bacteria in 96 wells microtiter plates at room temperature. The formed biofilms were assessed by tissue culture plate (TCP). Moreover, the nature of the biofilm was assessed by scanning electron microscopy (SEM) and PCR assay for detecting PIA genes, ciaA-D and FnBPA genes. RESULTS: this study showed that applied phages with 0.08 % benezenthonium chloride, for PIA biofilms, and 0.06 % ethanol, for proteinacious FnBPA biofilms, exerted 100 % eradication for MSSA biofilms and about 78 % of MRSA biofilms. The phage-based control of biofilms with chemical adjuvant showed significantly higher efficiency than that without adjuvant (P < 0.05). Moreover, FnBPA biofilms were more common in MRSA than in MSSA while PIA biofilms were more common in MSSA than in MRSA. And the most resistant type of biofilms to phage-based control was FnBPA in MRSA where 50 % of biofilms were reduced but not eradicated completely. CONCLUSIONS: It is concluded that PIA-disturbing agent and protein denaturing alcohol can increase the efficiency of attacking phages in accessing host cell walls and lysing them which in turn lead to much more efficient MRSA and MSSA biofilm treatment and prevention. PMID- 26558684 TI - Cotton Dust Exposure and Resulting Respiratory Disorders Among Home-Based Garment Workers. AB - Cotton dust exposures and resulting respiratory disorders among Thai home-based garment workers in Bangkok were explored. Structured interviews focused on occupational health assessments of respiratory disorders; workflow process observations, lung function screening tests, and garment dust density assessments were used to gather data. Results revealed that garment workers in this study had worked in home-based tailoring an average of 14.88 years; 88.5% reported average health status, only 2.6% currently smoked cigarettes, and 8.6% had impaired lung function. The prevalence of respiratory disorders in this occupational group was 25%. Significant respiratory tract signs and symptoms were associated with lung function capacity (odds ratio [OR] = 52.15, 95% confidence interval [CI] = [6.49, 419.60]). Long work hours and few preventive behaviors were significantly associated with respiratory disorders (OR = 2.89 and OR = 10.183, respectively). Improving working conditions at home and minimizing fabric dust exposure among garment workers are recommended. PMID- 26558685 TI - Ebola Care and Lack of Consensus on Personal Protective Respiratory Equipment. AB - The Ebola epidemic in West Africa presents a considerable occupational risk to the health personnel involved. The principal mode of virus transmission to health care personnel is through direct contact with the patient, although transmission by aerosols through the air may also occur. Many safety protocols have been suggested relating to personal protection and particularly respiratory protection. It is generally agreed that all health care workers should have easy access to personal protective equipment. However, the degree of respiratory safety escalates from a mask, to an adequate respirator, and finally to a whole body suit with integrated helmet and positive air pressure. Recent publications demonstrate a lack of consensus on the degree of safety necessary. The step from "safe enough" to being "absolutely safe" seems, in most countries, insurmountable because of costs and logistics. PMID- 26558686 TI - Associations between night work and BMI, alcohol, smoking, caffeine and exercise- a cross-sectional study. AB - BACKGROUND: Shift work is associated with negative health effects. Increased prevalence of several cardiovascular risk factors among shift workers/night workers compared with day workers have been shown resulting in increased risk of cardiovascular events among shift workers and night workers. Previous studies have taken a dichotomous approach to the comparison between day and night workers. The present study uses a continuous approach and provides such a new perspective to the negative effects of night work load as a possible risk factor for undesirable health effects. METHODS: This cross sectional study (The SUrvey of Shift work, Sleep and Health (SUSSH)) uses data collected from December 2008 to March 2009. The study population consists of Norwegian nurses. The study collected information about demographic and lifestyle factors: Body Mass Index (BMI), smoking habits, alcohol consumption, caffeine consumption and exercise habits. The lifestyle parameters were evaluated using multiple hierarchical regression and binary logistic regression. Number of night shifts worked last year (NNL) was used as operationalization of night work load. Adjustment for possible confounders were made. Obesity was defined as BMI > 30. Alcohol Consumption was evaluated using the short form of the Alcohol Use Disorders Identification Test Consumption (AUDIT-C). Data were analyzed using SPSS version 22. RESULTS: We had data from 2059 nurses. NNL was significantly and positively associated with BMI, both when evaluated against BMI as a continuous parameter (Beta = .055, p < .05), and against obesity (OR = 1.01, 95 % CI = 1.00-1.01). The AUDIT-C score was significantly and positively associated with hours worked per week (OR = 1.03, 95 % CI = 1.01-1.05). CONCLUSIONS: We found a positive significant association between night work load and BMI. This suggests that workers with a heavy night work load might need special attention and frequent health checks due to higher risk of undesirable health effects. PMID- 26558687 TI - Spread patterns of lymph nodes and the value of elective neck irradiation for esthesioneuroblastoma. AB - OBJECTIVES: This study was aimed to characterize patterns of lymphatic spread and assess the value of prophylactic elective neck irradiation (ENI) for esthesioneuroblastoma (ENB). METHODS: A retrospectively analysis of 116 patients with newly diagnosed ENB at our institution over 35-year period was undertaken. RESULTS: 32 patients (28%) presented lymph node metastasis at initial diagnosis, the common sites involved were level II, Ib, level III and VIIa. Among 80 N negative patients staged in Modified Kadish B/C, 50 patients were delivered with ENI, 30 patients were not. The 5-year regional failure-free survival was 98% in patients treated with ENI and 75% in patients without ENI (p=0.005), regional failure rate decreased significantly from 23% (7/30) to 2% (1/50) after ENI (p=0.002). Multivariate analysis also suggested that ENI was an independent favorable predictor for regional controlling (HR, 0.102; 95% CI: 0.012-0.848; p=0.035). CONCLUSIONS: This is the largest cohort of ENB so far in a single institute, and also the first detailed description of nodal spread patterns of N positive ENB. Elective neck irradiation reduced the regional failure significantly and should be recommended as a part of initial treatment strategy for patients staged with Modified Kadish B/C. PMID- 26558688 TI - From mice to men: Murine models of colorectal cancer for use in translational research. AB - Colorectal cancer (CRC) is the third most common carcinoma worldwide and despite advances in treatment, survival for patients with metastatic disease remains poor. With nearly 50% of patients developing metastases, in vivo investigation is essential to improve outcomes for these patients and numerous murine models of CRC have been developed to allow the study of chemoprevention and chemotherapy, in addition to improving our understanding of the pathogenesis of CRC. Selecting the most appropriate murine model for a specific application will maximize the conversion of potential therapies from the laboratory to clinical practice and requires an understanding of the various models available. This review will provide an overview of the murine models currently used in CRC research, discussing the limitations and merits of each and their most relevant application. It is aimed at the developing researcher, acting as a guide to prompt further reading in planning a specific study. PMID- 26558689 TI - Targeting fatty acid metabolism in cancer and endothelial cells. AB - Tumour angiogenesis has long been recognised as a target for anti-cancer therapy. The current approach of inhibiting the VEGF pathway has shown benefit in the clinic, though less than anticipated. We recently documented that glycolytic metabolism in endothelial cells (ECs) fuels angiogenesis, rendering it a possible target for inhibiting vascular growth in pathological conditions. More recently, we reported that the oxidation of fatty acids (FA) is irreplaceable for EC proliferation by providing carbons for de novo nucleotide synthesis. Furthermore, ECs are rather unique in this respect, creating novel therapeutic opportunities. Here, we review and compare the current understanding of FA utilisation in ECs and tumour cells (TCs). PMID- 26558690 TI - Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015. AB - In the absence of a vaccine or specific treatments for Ebola virus disease (EVD), early identification of cases is crucial for the control of EVD epidemics. We evaluated a new extraction kit (SpeedXtract (SE), Qiagen) on sera and swabs in combination with an improved diagnostic reverse transcription recombinase polymerase amplification assay for the detection of Ebola virus (EBOV-RT-RPA). The performance of combined extraction and detection was best for swabs. Sensitivity and specificity of the combined SE and EBOV-RT-RPA were tested in a mobile laboratory consisting of a mobile glovebox and a Diagnostics-in-a-Suitcase powered by a battery and solar panel, deployed to Matoto Conakry, Guinea as part of the reinforced surveillance strategy in April 2015 to reach the goal of zero cases. The EBOV-RT-RPA was evaluated in comparison to two real-time PCR assays. Of 928 post-mortem swabs, 120 tested positive, and the combined SE and EBOV-RT RPA yielded a sensitivity and specificity of 100% in reference to one real-time RT-PCR assay. Another widely used real-time RT-PCR was much less sensitive than expected. Results were provided very fast within 30 to 60 min, and the field deployment of the mobile laboratory helped improve burial management and community engagement. PMID- 26558691 TI - The pericyte antigen RGS5 in perivascular soft tissue tumors. AB - Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to alphaSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and alphaSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID- 26558693 TI - The rising incidence of severe sepsis based on administrative data - real change or coding-driven bias? PMID- 26558692 TI - Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia. AB - BACKGROUND: Poor targeting of antimicrobial drugs contributes to the millions of deaths each year from malaria, pneumonia, and other tropical infectious diseases. While malaria rapid diagnostic tests have improved use of antimalarial drugs, there are no similar tests to guide the use of antibiotics in undifferentiated fevers. In this study we estimate the diagnostic accuracy of two well established biomarkers of bacterial infection, procalcitonin and C-reactive protein (CRP) in discriminating between common viral and bacterial infections in malaria endemic settings of Southeast Asia. METHODS: Serum procalcitonin and CRP levels were measured in stored serum samples from febrile patients enrolled in three prospective studies conducted in Cambodia, Laos and, Thailand. Of the 1372 patients with a microbiologically confirmed diagnosis, 1105 had a single viral, bacterial or malarial infection. Procalcitonin and CRP levels were compared amongst these aetiological groups and their sensitivity and specificity in distinguishing bacterial infections and bacteraemias from viral infections were estimated using standard thresholds. RESULTS: Serum concentrations of both biomarkers were significantly higher in bacterial infections and malaria than in viral infections. The AUROC for CRP in discriminating between bacterial and viral infections was 0.83 (0.81-0.86) compared with 0.74 (0.71-0.77) for procalcitonin (p < 0.0001). This relative advantage was evident in all sites and when stratifying patients by age and admission status. For CRP at a threshold of 10 mg/L, the sensitivity of detecting bacterial infections was 95% with a specificity of 49%. At a threshold of 20 mg/L sensitivity was 86% with a specificity of 67%. For procalcitonin at a low threshold of 0.1 ng/mL the sensitivity was 90% with a specificity of 39%. At a higher threshold of 0.5 ng/ul sensitivity was 60% with a specificity of 76%. CONCLUSION: In samples from febrile patients with mono-infections from rural settings in Southeast Asia, CRP was a highly sensitive and moderately specific biomarker for discriminating between viral and bacterial infections. Use of a CRP rapid test in peripheral health settings could potentially be a simple and affordable measure to better identify patients in need of antibacterial treatment and part of a global strategy to combat the emergence of antibiotic resistance. PMID- 26558694 TI - Grain boundary resistance to amorphization of nanocrystalline silicon carbide. AB - Under the C displacement condition, we have used molecular dynamics simulation to examine the effects of grain boundaries (GBs) on the amorphization of nanocrystalline silicon carbide (nc-SiC) by point defect accumulation. The results show that the interstitials are preferentially absorbed and accumulated at GBs that provide the sinks for defect annihilation at low doses, but also driving force to initiate amorphization in the nc-SiC at higher doses. The majority of surviving defects are C interstitials, as either C-Si or C-C dumbbells. The concentration of defect clusters increases with increasing dose, and their distributions are mainly observed along the GBs. Especially these small clusters can subsequently coalesce and form amorphous domains at the GBs during the accumulation of carbon defects. A comparison between displacement amorphized nc-SiC and melt-quenched single crystal SiC shows the similar topological features. At a dose of 0.55 displacements per atom (dpa), the pair correlation function lacks long range order, demonstrating that the nc-SiC is fully amorphilized. PMID- 26558695 TI - Histone deacetylase inhibitors reduce WB-F344 oval cell viability and migration capability by suppressing AKT/mTOR signaling in vitro. AB - Histone deacetylase (HDAC) can blockDNA replication and transcription and altered HDAC expression was associated with tumorigenesis. This study investigated the effects of HDAC inhibitors on hepatic oval cells and aimed to delineate the underlying molecular events. Hepatic oval cells were treated with two different HDAC inhibitors, suberoylanilidehydroxamic acid (SAHA) and trichostatin-A (TSA). Cells were subjected to cell morphology, cell viability, cell cycle, and wound healing assays. The expression of proteins related to both apoptosis and the cell cycle, and proteins of the AKT/mammalian target of rapamycin (mTOR) signaling pathway were analyzed by Western blot. The data showed that HDAC inhibitors reduced oval cell viability and migration capability, and arrested oval cells at the G0/G1 and S phases of the cell cycle, in a dose- and time-dependent manner. HDAC inhibitors altered cell morphology and reduced oval cell viability, and downregulated the expression of PCNA, cyclinD1, c-Myc and Bmi1 proteins, while also suppressing AKT/mTOR and its downstream target activity. In conclusion, this study demonstrates that HDAC inhibitors affect oval cells by suppressing AKT/mTOR signaling. PMID- 26558696 TI - Thrombolytic protein from cobra venom with anti-adhesive properties. AB - A metalloproteinase anticoagulant toxin of molecular weight 66 kDa has been purified from the venom of Indian monocled cobra (Naja kaouthia). This toxin named as NKV 66 cleaved fibrinogen in a dose and time dependent manner. The digestion process was specific to Aalpha chain and cleaved fibrinogen to peptide fragments. NKV 66 completely liquefied the fibrin clots developed in vitro in 18 h. Plasma recalcification time and thrombin time were significantly prolonged following treatment of plasma with NKV 66. NKV 66 significantly inhibited ADP and collagen induced platelet aggregation in a dose dependent manner. It showed disintegrin like activity on A549 cells cultured in vitro. About 40% inhibition of adherence of A549 cells to matrix was observed following NKV 66 treatment also NKV 66 treated A549 cells were drastically inhibited from passing through the matrix in cell invasion assays in vitro, suggesting anti-adhesive properties of NKV 66. PMID- 26558698 TI - Factors affecting UK medical students' decision to train in urology: a national survey. AB - BACKGROUND: Our aim was to understand the specific factors which influence medical students' choice to train in urology, in order to attract the best and the brightest into the specialty during a challenging time for surgical training in the United Kingdom METHODS: A cross-sectional web-based survey was generated to evaluate: 1) perceptions of urology; 2) attitudes about urology as a career; 3) exposure to urology at medical school; and 4) proficiency in common urological procedures. The survey was sent to all 33 medical schools in the UK and advertised to all medical students. RESULTS: The survey received 488 responses were received from 14 medical schools; 59.8% of respondents did not consider a career in urology. Factors affecting a career choice in urology included: 1) year of study; 2) male gender; 3) favorable perceptions of urology; 4) favorable attitudes about urology as a career; 5) more hours of urology teaching in preclinical years; 6) attendance at urology theatre sessions; 7) confidence in performing urological procedures; and 8) more attempts at male catheterization. The commonest reason for not considering urology was inadequate exposure to urology. Students in Year 3 were more likely to consider urology than final-year students, due to multifactorial reasons. CONCLUSIONS: Year of study is a novel factor affecting students' consideration of urology as a career. This paper clearly shows that early and sustained exposure to urology positively correlated with considering a career in urology. Urologists must be more active in promoting the specialty to medical students. PMID- 26558697 TI - Mangiferin regulates cognitive deficits and heme oxygenase-1 induced by lipopolysaccharide in mice. AB - Accumulating evidence reveals that lipopolysaccharide (LPS) can induce neuroinflammation, ultimately leading to cognitive deficits. Mangiferin, a natural glucoxilxanthone, is known to possess various biological activities. The present study aimed to investigate the effects of mangiferin on LPS-induced cognitive deficits and explore the underlying mechanisms. Brain injury was induced in mice via intraperitoneal LPS injection (1mg/kg) for five consecutive days. Mangiferin was orally pretreatmented (50mg/kg) for seven days and then treatmented (50mg/kg) for five days after LPS injection. The Morris water maze was used to detect changes in cognitive function. Immunohistochemical and immunoblotting were respectively performed to measure the expression of interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the hippocampus. The results showed that mangiferin can ameliorate cognitive deficits. Moreover, mangiferin decreased LPS-induced IL-6 production and increase HO-1 in the hippocampus. Taken together, these results suggest that mangiferin attenuates LPS-induced cognitive deficits, which may be potentially linked to modulating HO-1 in the hippocampus. PMID- 26558699 TI - Maternal Childhood Adversity, Prepregnancy Obesity, and Gestational Weight Gain. AB - INTRODUCTION: Growing evidence suggests that exposure to childhood adversity may influence obesity across the life course. High maternal weight complicates pregnancy and increases the risk of child obesity. This study examined the association between maternal childhood adversity and pregnancy-related weight in a large U.S. METHODS: Data on 6,199 pregnancies from 2,873 women followed from 1979 to 2012 by the National Longitudinal Survey of Youth 1979 were analyzed in 2014. Associations between three adversity exposures before age 18 years (history of physical abuse, alcohol problems, or mental illness in the household) and two maternal weight outcomes (prepregnancy obesity and excessive gestational weight gain) were modeled separately using survey-adjusted log-binomial models. RESULTS: After adjusting for race/ethnicity and early-life socioeconomic factors, childhood physical abuse was associated with a 60% increase in the risk of prepregnancy obesity (adjusted risk ratio=1.6, 95% CI=1.1, 2.2). Household alcohol abuse was associated with a 30% increase in prepregnancy obesity (adjusted risk ratio=1.3, 95% CI=1.0, 1.7), as was household mental illness (adjusted risk ratio=1.3, 95% CI=0.8, 1.9), but the mental illness exposure was not significant. Physical abuse and household alcohol abuse were associated with a significant 20% increase in the risk of excessive gestational weight gain; mental illness was not. CONCLUSIONS: Adversity in early life may affect maternal weight before and during pregnancy. Screening and treating women of reproductive age for childhood adversity and its negative effects could significantly reduce obesity-related health outcomes for women and their children. PMID- 26558700 TI - Using GPS Data to Study Neighborhood Walkability and Physical Activity. AB - INTRODUCTION: Urban form characteristics intended to support pedestrian activity, collectively referred to as neighborhood walkability, are thought to increase total physical activity. However, little is known about how neighborhood walkability influences utilization of neighborhood space by residents and their overall physical activity. METHODS: Sociodemographic information and data on mobility and physical activity over 1-week periods measured by GPS loggers and accelerometers were collected from 803 residents of New York City between November 2010 and November 2011. Potentially accessible neighborhood areas were defined as land area within a 1-kilometer distance of the subject's home (radial buffer) and within a 1-kilometer journey on the street network from the home (network buffer). To define actual areas utilized by subjects, a minimum convex polygon was plotted around GPS waypoints falling within 1 kilometer of the home. A neighborhood walkability scale was calculated for each neighborhood area. Data were analyzed in 2014. RESULTS: Total residential neighborhood space utilized by subjects was significantly associated with street intersection density and was significantly negatively associated with residential density and subway stop density within 1 kilometer of the home. Walkability scale scores were significantly higher within utilized as compared with non-utilized neighborhood areas. Neighborhood walkability in the utilized neighborhood area was positively associated with total weekly physical activity (32% [95% CI=17%, 49%] more minutes of moderate-equivalent physical activity across the interquartile range of walkability). CONCLUSION: Neighborhood walkability is associated with neighborhood spaces utilized by residents and total weekly physical activity. PMID- 26558701 TI - Monitoring of the retinoic acid receptor-retinoid X receptor dimerization upon DNA binding by native mass spectrometry. AB - Identifying protein-DNA interactions is essential to understand the regulatory networks of cells and their influence on gene expression. In this study, we use native electrospray mass spectrometry (ESI-MS) to investigate how the heterodimerization of retinoic acid receptor-retinoid X receptor (RAR-RXR) is mediated by DNA sequence. In presence of various RAR response elements (RAREs), three oligomeric states of RAR-RXR DNA binding domains (DBDs) bound to RAREs (monomer, homo- or heterodimers) were detected and individually monitored to follow subunit assembly and disassembly upon RAREs' abundancy or sequence. In particular, a cooperative heterodimerization was shown with RARb2 DR5 (5 base pair spaced direct repeat) while a high heterogeneity reflecting random complex formation could be observed with the DR0 response elements, in agreement with native gel electrophoresis data or molecular modeling. Such MS information will help to identify the composition of species formed in solution and to define which DR sequence is specific for RAR-RXR heterodimerization. PMID- 26558703 TI - Chryseobacterium frigidum sp. nov., isolated from high-Arctic tundra soil, and emended descriptions of Chryseobacterium bernardetii and Chryseobacterium taklimakanense. AB - A yellow, Gram-reaction-negative, non-motile, aerobic bacterium, designated D07T, was isolated from a tundra soil near Ny-Alesund, Svalbard archipelago, Norway (78 degrees N). Growth occurred at 4-37 degrees C (optimum 28-30 degrees C) and at pH 6.0-9.0 (optimum pH 7.0-8.0). The strain produced flexirubin-type pigments. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain D07T belonged to the genus Chryseobacterium in the family Flavobacteriaceae. The 16S rRNA gene sequence of this strain showed 93.83 and 93.31 % sequence similarity, respectively, to those of Chryseobacterium contaminans C26T and Chryseobacterium taklimakanense X-65T. Strain D07T contained anteiso-C15 : 0 (25.91 %), iso-C15 : 0 (16.05 %), iso-C16 : 0 3-OH (9.64 %), iso-C16 : 0 (9.42 %) and iso-C14 : 0 (7.36 %) as the predominant cellular fatty acids, MK-6 as the major respiratory quinone and phosphatidylethanolamine, five unknown aminolipids and three unknown lipids as the main polar lipids. The DNA G+C content was 49.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain D07T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium frigidum sp. nov. is proposed. The type strain is D07T ( = CCTCC AB 2011160T = KCTC 42897T). Emended descriptions of Chryseobacterium bernardetii and Chryseobacterium taklimakanense are also provided. PMID- 26558704 TI - Floral traits driving reproductive isolation of two co-flowering taxa that share vertebrate pollinators. AB - Floral attributes evolve in response to frequent and efficient pollinators, which are potentially important drivers of floral diversification and reproductive isolation. In this context, we asked, how do flowers evolve in a bat-hummingbird pollination system? Hence, we investigated the pollination ecology of two co flowering Ipomoea taxa (I. marcellia and I. aff. marcellia) pollinated by bats and hummingbirds, and factors favouring reproductive isolation and pollinator sharing in these plants. To identify the most important drivers of reproductive isolation, we compared the flowers of the two Ipomoea taxa in terms of morphometry, anthesis and nectar production. Pollinator services were assessed using frequency of visits, fruit set and the number of seeds per fruit after visits. The studied Ipomoea taxa differed in corolla size and width, beginning and duration of anthesis, and nectar attributes. However, they shared the same diurnal and nocturnal visitors. The hummingbird Heliomaster squamosus was more frequent in I. marcellia (1.90 visits h(-1)) than in I. aff. marcellia (0.57 visits h(-1)), whereas glossophagine bats showed similar visit rates in both taxa (I. marcellia: 0.57 visits h(-1) and I. aff. marcellia: 0.64 visits h(-1)). Bat pollination was more efficient in I. aff. marcellia, whereas pollination by hummingbirds was more efficient in I. marcellia. Differences in floral attributes between Ipomoea taxa, especially related to the anthesis period, length of floral parts and floral arrangement in the inflorescence, favour reproductive isolation from congeners through differential pollen placement on pollinators. This bat hummingbird pollination system seems to be advantageous in the study area, where the availability of pollinators and floral resources changes considerably throughout the year, mainly as a result of rainfall seasonality. This interaction is beneficial for both sides, as it maximizes the number of potential pollen vectors for plants and resource availability for pollinators. PMID- 26558702 TI - Mechanosensitive TRPM7 mediates shear stress and modulates osteogenic differentiation of mesenchymal stromal cells through Osterix pathway. AB - Microenvironments that modulate fate commitments of mesenchymal stromal cells (MSCs) are composed of chemical and physical cues, but the latter ones are much less investigated. Here we demonstrate that intermittent fluid shear stress (IFSS), a potent and physiologically relevant mechanical stimulus, regulates osteogenic differentiation of MSCs through Transient receptor potential melastatin 7 (TRPM7)-Osterix axis. Immunostaining showed the localization of TRPM7 near or at cell membrane upon IFSS, and calcium imaging analysis demonstrated the transient increase of cytosolic free calcium. Expressions of osteogenic marker genes including Osterix, but not Runx2, were upregulated after three-hour IFSS. Phosphorylation of p38 and Smad1/5 was promoted by IFSS as well. TRPM7 gene knockdown abolished the promotion of bone-related gene expressions and phosphorylation. We illustrate that TRPM7 is mechanosensitive to shear force of 1.2 Pa, which is much lower than 98 Pa pressure loading reported recently, and mediates distinct mechanotransduction pathways. Additionally, our results suggest the differential roles of TRPM7 in endochondral and intramembranous ossification. Together, this study elucidates the mechanotransduction in MSCs fate commitments and displays an efficient mechano-modulation for MSCs osteogenic differentiation. Such findings should be taken into consideration when designing relevant scaffolds and microfluidic devices for osteogenic induction in the future. PMID- 26558705 TI - Constraints on coastal dune invasion for a notorious plant invader. AB - Although most biological invasions are not successful, relatively few studies have examined otherwise notorious invaders in systems where they are not highly problematic. The annual grass Bromus tectorum is a dominant invader in western North America, but is usually confined to human-dominated and disturbed systems (e.g. roadsides and parking lots) in the East where it remains virtually unstudied. This study aims to address fundamental ecological questions regarding B. tectorum in a Cape Cod dune ecosystem. (i) What is the range of variation in population dynamics and the potential for population growth? (ii) Which factors influence its local abundance and distribution? We observed substantial variation in population dynamics over 3 years, with the number of adult B. tectorum individuals increasing substantially between the first 2 years (lambda = 9.24) and then decreasing (lambda = 0.43). Population growth in terms of total seeds was similarly variable, but to a lesser extent (lambda = 2.32 followed by lambda = 0.32). Experimental soil disturbance led to a more than 10-fold increase in mean seedling emergence, and high sensitivity to differences in emergence carried this effect through the life cycle. In contrast, barriers to seed dispersal had no effect on population dynamics, suggesting limited dispersal in this system. Across the landscape, the presence of B. tectorum was associated with areas of higher plant diversity as opposed to those with a strong dominant (e.g. the foredune, dominated by Ammophila breviligulata, or low heathlands, characterized by Hudsonia tomentosa and Arctostaphylos uva-ursi). Overall, we find that B. tectorum is capable of both substantial population growth and decline in a dune ecosystem, but is likely limited without disturbance and dispersal agents. Thus, management actions that restrict dune access (e.g. for nesting habitat) likely have the co-benefit of limiting the invasive potential of B. tectorum. PMID- 26558706 TI - Trade-off between competition and facilitation defines gap colonization in mountains. AB - Recent experimental observations show that gap colonization in small-stature (e.g. grassland and dwarf shrubs) vegetation strongly depends on the abiotic conditions within them. At the same time, within-gap variation in biotic interactions such as competition and facilitation, caused by distance to the gap edge, would affect colonizer performance, but a theoretical framework to explore such patterns is missing. Here, we model how competition, facilitation and environmental conditions together determine the small-scale patterns of gap colonization along a cold gradient in mountains, by simulating colonizer survival in gaps of various sizes. Our model adds another dimension to the known effects of biotic interactions along a stress gradient by focussing on the trade-off between competition and facilitation in the within-gap environment. We show that this trade-off defines a peak in colonizer survival at a specific distance from the gap edge, which progressively shifts closer to the edge as the environment gets colder, ultimately leaving a large fraction of gaps unsuitable for colonization in facilitation-dominated systems. This is reinforced when vegetation size and temperature amelioration are manipulated simultaneously with temperature in order to simulate an elevational gradient more realistically. Interestingly, all other conditions being equal, the magnitude of the realized survival peak was always lower in large than in small gaps, making large gaps harder to colonize. The model is relevant to predict effects of non-native plant invasions and climate warming on colonization processes in mountains. PMID- 26558707 TI - Acute effects of stretching on maximal muscle strength and functional performance: A systematic review of Japanese-language randomised controlled trials. AB - BACKGROUND: There is no consensus in the English-language literature regarding the best types or dosages of stretching to maximise muscle strength and functional performance. It is possible that primary research published in non English languages provides different insights, and could add to the body of international knowledge. PURPOSE: This systematic review aimed to identify and evaluate Japanese-language randomised controlled trials (RCTs) investigating acute effects of stretching on maximal strength and functional performance. METHODS: Three Japanese databases and five English databases were searched from inception to 24 March 2015. Only Japanese-language RCTs examining acute effects of stretching on maximal strength and/or functional performance were included. Risk of bias in included studies was assessed using Physiotherapy Evidence Database scale. GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach was applied to evaluate the quality of evidence. Descriptive synthesis was attempted. RESULTS: Seven RCTs with variable methodological quality were included. No two studies were the same, thus meta-analysis was not possible. Descriptively, because of heterogeneity of interventions and outcome measures, it was not possible to identify consensus on the benefits of stretching. GRADE approach indicated low to very low quality evidence for this topic. CONCLUSION: This review of Japanese-language RCTs provided no additional information to strengthen or challenge the current English-language evidence base on acute effects of stretching on maximal strength and performance. Future Japanese language studies should address methodological flaws exposed in this review and incorporate functional outcome measures to strengthen the international evidence base. PMID- 26558708 TI - Ventral Striatal Activation During Reward Processing in Psychosis: A Neurofunctional Meta-Analysis. AB - IMPORTANCE: Abnormal reward processing is suggested to underlie the formation of psychotic symptoms, likely driven by elevated ventral striatal (VS) dopamine levels. Functional magnetic resonance imaging studies reveal alterations of VS activity during reward processing in patients with chronic psychosis and first episode of psychosis, as well as individuals at high risk for psychosis, but findings are inconclusive, conflicting, and difficult to subject to meta-analysis without introducing bias because several studies reported that findings were not statistically significant but did not report statistics. OBJECTIVE: To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing. DATA SOURCES: Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews. STUDY SELECTION: Functional magnetic resonance imaging studies comparing VS activity during monetary reward processing between patients with schizophrenia spectrum disorders or clinical or genetic high-risk state for psychosis and healthy controls. DATA EXTRACTION AND SYNTHESIS: Statistics and thresholds related to the main outcome measures and potential moderators were independently retrieved by 2 investigators. Effect sizes were analyzed using MetaNSUE, a random-effects method that enables the unbiased inclusion of nonstatistically significant unreported effects. MAIN OUTCOMES AND MEASURES: Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients. RESULTS: The meta-analysis included 23 studies (917 patients) for reward anticipation, 9 studies (358 patients) for reward feedback, and 8 studies (314 patients) for reward prediction error. We found significant bilateral VS hypoactivation during reward anticipation (23 studies, n = 917) in patients compared with healthy controls (left/right Cohen d, -0.50/-0.70; P < .001). Left VS abnormality was more severe in patients with high scores of negative symptoms during reward anticipation (r = -0.41; P < .001). Patients also showed hypoactivation during reward feedback (left/right d, -0.57/-0.56; P < .001). Simulations showed that exclusion of studies with nonstatistically significant unreported effects was associated with a strong bias (d bias = 0.22), whereas estimations using MetaNSUE were unbiased even when statistics were seldom reported (d bias < 0.001). CONCLUSIONS AND RELEVANCE: This meta-analysis provides evidence that patients with psychosis demonstrate VS hypoactivation during reward anticipation. The assessment of VS prediction errors seems to be promising, but more studies are needed to draw valid conclusions. PMID- 26558709 TI - Identifying N2O formation and emissions from a full-scale partial nitritation reactor. AB - In this study, N2O formation and emissions from a full-scale partial nitritation (SHARON) reactor were identified through a three-weeks monitoring campaign during which the off-gas was analysed for N2O, O2, CO2 and NO. The overall N2O emission was 3.7% of the incoming ammonium load. By fitting the N2O emission to a theoretical gas stripping profile, the N2O emissions could be assigned to aerobically formed N2O and N2O formed under anoxic conditions. This was further substantiated by liquid N2O measurements. Under standard operation, 70% of the N2O emission was attributed to anoxic N2O formation. Dedicated experiments revealed that low dissolved oxygen concentrations (<1.0 gO2.m(-3)) and longer anoxic periods resulted in an increased N2O emission. Minimising or avoiding anoxic conditions has the highest effect in lowering the N2O emissions. As an additional result, the use of the off-gas N2O concentration measurements to monitor the gas-liquid mass transfer rate coefficient (kLa) during dynamic reactor operation was demonstrated. PMID- 26558710 TI - Cotransport of bacteria with hematite in porous media: Effects of ion valence and humic acid. AB - This study investigated the influence of multiple colloids (hematite and humic acid) on the transport and deposition of bacteria (Escherichia coli) in packed porous media in both NaCl (5 mM) and CaCl2 (1 mM) solutions at pH 6. Due to the alteration of cell physicochemical properties, the presence of hematite and humic acid in cell suspensions significantly affected bacterial transport and deposition in quartz sand. Specifically, the presence of hematite (5 mg/L) decreased cell transport (increased cell deposition) in quartz sand in both NaCl and CaCl2 solutions, which could be attributed to the less negative overall zeta potentials of bacteria induced by the adsorption of positively charged hematite onto cell surfaces. The presence of a low concentration (0.1 mg/L) of humic acid in bacteria and hematite mixed suspensions reduced the adsorption of hematite onto cell surfaces, leading to increased cell transport in quartz sand in NaCl solutions, whereas, in CaCl2 solutions, the presence of 0.1 mg/L humic acid increased the formation of hematite-cell aggregates and thus decreased cell transport in quartz sand. When the concentration of humic acid was increased to 1 mg/L, enhanced cell transport was observed in both NaCl and CaCl2 solutions. The decreased adsorption of hematite onto cell surfaces as well as the competition of deposition sites on quartz sand with bacteria by the suspended humic acid contributed to the increased cell transport. PMID- 26558711 TI - Opportunities to Improve Care for Surgery Patients. PMID- 26558712 TI - Inbreeding and homozygosity in breast cancer survival. AB - Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner. PMID- 26558713 TI - Ictal vomiting as a sign of temporal lobe epilepsy confirmed by stereo-EEG and surgical outcome. AB - Vomiting is uncommon in patients with epilepsy and has been reported in both idiopathic and symptomatic epilepsies. It is presumed to originate in the anterior part of the temporal lobe or insula. To date, 44 cases of nonidiopathic focal epilepsy and seizures associated with ictal vomiting have been reported. Of the 44 cases, eight were studied using invasive exploration (3 stereo-EEG/5 subdural grids). Here, we report a 4-year-and-7-month-old patient with a history of febrile convulsion in the second year of life and who developed episodes of vomiting and complex partial seizures at 3 years of age. Scalp EEG showed no electrical modification during vomiting while the complex partial seizure displayed a clear right temporal origin. Brain MR showed hippocampal volume reduction with mild diffuse blurring of the temporal lobe. Stereoelectroencephalography study confirmed the mesiotemporal origin of the seizures and showed that the episodes of vomiting were strictly related to an ictal discharge originating in the mesial temporal structures without insular diffusion. The patient is now seizure-free (18 months) after removal of the right anterior and mesial temporal structures. In all the reported patients, seizures seemed to start in mesial temporal structures. The grid subgroup is more homogeneous, and the most prominent characteristic (4/5) is the involvement of both mesial and lateral temporal structures at the time of vomiting. In the S-EEG group, there is evidence of involvement of either the anterior temporal structures alone (2/3) or both insular cortices (1/3). Our case confirms that vomiting could occur when the ictal discharge is limited to the anterior temporal structure without insular involvement. Regarding the pathophysiology of vomiting, the role of subcortical structures such as the dorsal vagal complex and the central pattern generators (CPG) located in the reticular area is well established. Vomiting as an epileptic phenomenon seems to be related to the involvement of temporal structures, mainly mesial structures (amygdala) and with an uncertain role of the insula. An intriguing hypothesis is that the ictal discharge in mesial structures determines seizure manifestation that could be explained not only by tonic activation of the cortex, but also by 'release' (reduction of inhibition?) of the CPG responsible for involuntary motor behaviors. PMID- 26558714 TI - Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome. AB - Down syndrome (DS) is the most common cause of genetic intellectual disability, and the trisomy 21 is associated with more than 80 clinical traits, including higher risk for epilepsy. Several hypotheses have been put forward to explain the mechanisms underlying increased seizure susceptibility in DS: inherent structural brain abnormalities, abnormal cortical lamination, disruption of normal dendritic morphology, and underdeveloped synaptic profiles. A deficiency or loss of GABA inhibition is hypothesized to be one of the main alterations related to the epileptogenic process. Paradoxically, enhanced GABA inhibition has also been reported to promote seizures. One major functional abnormality observed in the brains of individuals and mouse models with DS appears to be an imbalance between excitatory and inhibitory neurotransmission, with excessive inhibitory brain function. This review discusses the GABAergic system in the human DS brain and the possible implication of the GABAergic network circuit in the epileptogenic process in individuals where the pathogenetic basis for epilepsy is unknown. PMID- 26558715 TI - Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape. AB - Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs. PMID- 26558716 TI - Influence of age and sex on the longitudinal relaxation time, T1, of the lung in healthy never-smokers. AB - BACKGROUND: As several studies have provided evidence that lung disease affects the T1 of the human lung, our purpose was to investigate the effect of age on the T1-relaxation time in the lungs of healthy never-smokers, including group difference between sexes. MATERIALS AND METHODS: The Snapshot FLASH pulse sequence (inversion recovery with multiple gradient echo read-outs) was used to quantify lung T1 in 30 healthy never-smoking volunteers at 1.5 Tesla. Measurements were performed under breathhold of a tidal inspiration. Additionally, subjects underwent clinical MRI and pulmonary function tests. A linear regression model of T1 as a function of age and sex was tested. RESULTS: The slope of lung T1 at tidal end-inspiration as a function of age was statistically different between males and females (P < 0.001). In a linear regression model of T1 as a function of age and sex, females have slope of -4.1 ms/year (95% confidence interval [CI], [-5.2, -3.0]) at P < 0.001, and males 0.064 ms/year (95% CI, [-1.2, 1.1]) at P = 0.9, with a whole model R(2) = 0.83. CONCLUSION: The observed dependencies of lung T1 on age and sex are here attributed to a previously reported difference in blood T1 between sexes, and a previously reported decrease of pulmonary blood volume with increasing age. This may have implications for the interpretation of lung T1 measurements in both healthy individuals and patients. PMID- 26558717 TI - Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. AB - The C-type lectin receptor (CTLR), Clec4d (MCL, CLECSF8), is a member of the Dectin-2 cluster of CTLRs, which also includes the related receptors Mincle and Dectin-2. Like Mincle, Clec4d recognizes mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti-mycobacterial immunity in mouse and man. Here, we characterized receptor expression in naive mice, under inflammatory conditions, and during Mycobacterium bovis BCG infection using newly generated monoclonal antibodies. In naive mice, Clec4d was predominantly expressed on myeloid cells within the peritoneal cavity, blood, and bone marrow. Unexpectedly, basal expression of Clec4d was very low on leukocytes in the lung. However, receptor expression was significantly upregulated on pulmonary myeloid cells during M. bovis BCG infection. Moreover, Clec4d expression could be strongly induced in vitro and in vivo by various microbial stimuli, including TLR agonists, but not exogenous cytokines. Notably, we show that Clec4d requires association with the signaling adaptor FcRgamma and Mincle, but not Dectin-2, for surface expression. In addition, we provide evidence that Clec4d and Mincle, but not Dectin-2, are interdependently coregulated during inflammation and infection. These data show that Clec4d is an inducible myeloid expressed CTLR in mice, whose expression is tightly linked to that of Mincle. PMID- 26558719 TI - Metabolic syndrome in schizophrenia patients associated with poor premorbid school performance in early adolescence. AB - OBJECTIVE: More than 40% of patients with schizophrenia have an additional diagnosis of the metabolic syndrome (MS), possibly related to poor cognition. This study investigated premorbid and current cognitive functioning in schizophrenia and co-occurrence of MS. METHOD: A total of 104 participants with schizophrenia with MS and 142 without MS were included. Neuropsychological assessment was carried out using the Wechsler Adult Intelligence Scale-III, Word Learning Task, and Continuous Performance Test-HQ. Premorbid functioning was assessed retrospectively with the Premorbid Adjustment Scale. anovas were used to examine differences between participants with and without MS. RESULTS: Subjects with and without MS did not differ concerning current, lifetime and amount substance use, duration/severity of illness, parental socioeconomic status (SES), and type/amount of antipsychotic medication. We found that poor school performance between the ages 12 and 16 is associated with MS in schizophrenia. Educational level and current cognitive functioning in participants with MS deviate as compared to those without MS. CONCLUSION: Subjects with MS had impaired premorbid cognition in adolescence and lower educational achievement, irrespective of parental SES. This suggests poor premorbid cognitive functioning is a risk factor for metabolic complications later in life. Future studies are needed to examine whether cognitive interventions have beneficial effects on general health in schizophrenia. PMID- 26558718 TI - An investigation of causes of false positive single nucleotide polymorphisms using simulated reads from a small eukaryote genome. AB - BACKGROUND: Single Nucleotide Polymorphisms (SNPs) are widely used molecular markers, and their use has increased massively since the inception of Next Generation Sequencing (NGS) technologies, which allow detection of large numbers of SNPs at low cost. However, both NGS data and their analysis are error-prone, which can lead to the generation of false positive (FP) SNPs. We explored the relationship between FP SNPs and seven factors involved in mapping-based variant calling - quality of the reference sequence, read length, choice of mapper and variant caller, mapping stringency and filtering of SNPs by read mapping quality and read depth. This resulted in 576 possible factor level combinations. We used error- and variant-free simulated reads to ensure that every SNP found was indeed a false positive. RESULTS: The variation in the number of FP SNPs generated ranged from 0 to 36,621 for the 120 million base pairs (Mbp) genome. All of the experimental factors tested had statistically significant effects on the number of FP SNPs generated and there was a considerable amount of interaction between the different factors. Using a fragmented reference sequence led to a dramatic increase in the number of FP SNPs generated, as did relaxed read mapping and a lack of SNP filtering. The choice of reference assembler, mapper and variant caller also significantly affected the outcome. The effect of read length was more complex and suggests a possible interaction between mapping specificity and the potential for contributing more false positives as read length increases. CONCLUSIONS: The choice of tools and parameters involved in variant calling can have a dramatic effect on the number of FP SNPs produced, with particularly poor combinations of software and/or parameter settings yielding tens of thousands in this experiment. Between-factor interactions make simple recommendations difficult for a SNP discovery pipeline but the quality of the reference sequence is clearly of paramount importance. Our findings are also a stark reminder that it can be unwise to use the relaxed mismatch settings provided as defaults by some read mappers when reads are being mapped to a relatively unfinished reference sequence from e.g. a non-model organism in its early stages of genomic exploration. PMID- 26558720 TI - HIV protease inhibitors disrupt astrocytic glutamate transporter function and neurobehavioral performance. AB - OBJECTIVE: The neurotoxic actions of the HIV protease inhibitors, amprenavir (APV) and lopinavir (LPV) were investigated. DESIGN: With combination antiretroviral therapy (cART), HIV-infected persons exhibit neurocognitive impairments, raising the possibility that cART might exert adverse central nervous system (CNS) effects. We examined the effects of LPV and APV using in vitro and in-vivo assays of CNS function. METHODS: Gene expression, cell viability and amino-acid levels were measured in human astrocytes, following exposure to APV or LPV. Neurobehavioral performance, amino-acid levels and neuropathology were examined in HIV-1 Vpr transgenic mice after treatment with APV or LPV. RESULTS: Excitatory amino-acid transporter-2 (EAAT2) expression was reduced in astrocytes treated with LPV or APV, especially LPV (P < 0.05), which was accompanied by reduced intracellular L-glutamate levels in LPV-treated cells (P < 0.05). Treatment of astrocytes with APV or LPV reduced the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 (P < 0.05) although cell survival was unaffected. Exposure of LPV to astrocytes augmented glutamate-evoked transient rises in [Cai] (P < 0.05). Vpr mice treated with LPV showed lower concentrations of L-glutamate, L-aspartate and L-serine in cortex compared with vehicle-treated mice (P < 0.05). Total errors in T-maze assessment were increased in LPV and APV-treated animals (P < 0.05). EAAT2 expression was reduced in the brains of protease inhibitor-treated animals, which was associated with gliosis (P < 0.05). CONCLUSION: These results indicated that contemporary protease inhibitors disrupt astrocyte functions at therapeutic concentrations with enhanced sensitivity to glutamate, which can lead to neurobehavioral impairments. ART neurotoxicity should be considered in future therapeutic regimens for HIV/AIDS. PMID- 26558721 TI - Plasmacytoid dendritic cells and myeloid cells differently contribute to B-cell activating factor belonging to the tumor necrosis factor superfamily overexpression during primary HIV infection. AB - BACKGROUND: After describing heightened levels of circulating B-cell-activating factor belonging to the tumor necrosis factor superfamily (BAFF) as well as changes in B-cell phenotype and functions during acute infection by simian immunodeficiency virus, we wanted to determine whether and by which cells BAFF was over-expressed in primary HIV-infected (PHI) patients. DESIGN AND METHODS: We simultaneously examined circulating BAFF levels by ELISA and membrane-bound BAFF (mBAFF) expression by flow cytometry in peripheral blood mononuclear cells of healthy donors and PHI patients followed for 6 months. We also examined whether HIV-1 modifies BAFF expression or release in various myeloid cells and plasmacytoid dendritic cells (pDC) in vitro. RESULTS: Circulating BAFF levels were transiently increased at enrolment. They positively correlated with CXCL10 levels and inversely with B-cell counts. Whereas mBAFF was expressed by most pDC and on a fraction of intermediate monocytes in healthy donors, the frequency of mBAFF cells significantly increased among nonclassical monocytes and CD1c dendritic cells but decreased among pDC in PHI patients. In contrast to myeloid cells, pDC never released BAFF upon stimulation. Their mBAFF expression was enhanced by HIV-1, independently of type I IFN. CONCLUSION: Our findings reveal that the pattern of BAFF expression by myeloid cells and pDC is altered in PHI patients and constitutes a valuable marker of immune activation whose circulating levels correlate with CXCL10 levels. Due to their homing in different tissue areas, pDC and myeloid cells might target different B-cell subsets through their mBAFF expression or soluble BAFF release. PMID- 26558723 TI - Higher tenofovir exposure is associated with longitudinal declines in kidney function in women living with HIV. AB - OBJECTIVE: Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function. DESIGN: This is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)]. METHODS: Multivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4 cell count, and HIV viral load. RESULTS: Of the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean +/- standard error: 80 +/- 4.3 vs. 104 +/- 2.5 ml/min per 1.73 m, P < 0.0001). By year 7, this difference widened (72 +/- 4.9 vs. 105 +/- 2.9, P < 0.0001). After multivariable adjustment, TFV AUC in the highest tertile remained associated with lower eGFRcr relative to values in the lowest tertile at both baseline (-15 ml/min per 1.73 m, P = 0.0047) and year 7 ( 23 ml/min per 1.73 m, P = 0.0002). CONCLUSION: Through intensive TFV pharmacokinetic sampling, we found a strong association between greater TFV exposure and subsequent decline in kidney function. Variations in TFV drug exposure may partially account for subsequent nephrotoxicity in persons infected with HIV. PMID- 26558724 TI - Balance between activation and regulation of HIV-specific CD8+ T-cell response after modified vaccinia Ankara B therapeutic vaccination. AB - BACKGROUND: The causes of HIV-vaccines failure are poorly understood. Therapeutic vaccination with modified vaccinia Ankara (MVA)-B in HIV-1-infected individuals did not control the virus upon analytical treatment interruption (ATI). We investigated whether the functional characteristics of HIV-specific CD8 T-cell responses stimulated by this vaccine, and the level of exhaustion of these cells might explain these results. METHODS: Twenty-one HIV-1 chronically infected patients on combination antiretroviral therapy, included in the therapeutic vaccine trial RISVAC03, were studied: 13 immunized and eight controls. Functional characteristics, cytotoxic potential and exhaustion of HIV-specific CD8 T cells, were evaluated by polychromatic flow cytometry. Differences between groups were tested using nonparametric tests. RESULTS: MVA-B vaccine induced an increase in HIV-specific CD8 T-cell response, but also increased their levels of exhaustion. At week 18 (following three immunizations) the level of response increased with respect to baseline (P = 0.02). A significant increase at weeks 18 and 24 (ATI) in granzyme B content was also observed. Interestingly, an increase in expression of exhaustion markers was found at weeks 18 (P = 0.006) and 24 (P = 0.01). However, there was no significant change in the functional profile of vaccine induced CD8 cells. At week 36, in parallel to the rebound of plasma viremia after 12 weeks ATI, a significant increase in the level of CD8 response, in granzyme B content and in exhaustion markers expression, was observed in both groups. CONCLUSION: We show that therapeutic vaccination with MVA-B tilts the balance between activation and regulation of the response of HIV-specific CD8 T cells towards regulation, which impacts on the viral rebound after ATI. PMID- 26558725 TI - Sex work and HIV incidence among people who inject drugs. AB - OBJECTIVE: Although the global burden of HIV infection among sex workers (SW) has been well recognized, HIV-related risks among sex workers who inject drugs (SW IDU) have received less attention. We investigated the relationship between sex work and HIV incidence among people who inject drugs (IDU) in a Canadian setting. DESIGN: Prospective cohort study. METHODS: Using Kaplan-Meier methods and the extended Cox regression, we compared HIV incidence among SW-IDU and non-SW-IDU in Vancouver, Canada, after adjusting for potential confounders. RESULTS: Between 1996 and 2012, 1647 participants were included in the study, including 512 (31.1%) IDU engaged in sex work. At 5 years the HIV cumulative incidence was higher among SW-IDU in comparison to other IDU (12 vs. 7%, P = 0.001). In unadjusted Cox regression analyses, HIV incidence among SW-IDU was also elevated [relative hazard: 1.69; 95% confidence interval (CI): 1.13-2.53]. However, in a multivariable analysis, sex work did not remain associated with HIV infection (adjusted relative hazard: 0.74; 95% CI: 0.45-1.20), with cocaine injection appearing to account for the elevated risk for HIV infection among SW-IDU. CONCLUSION: These data suggest that local SW-IDU have elevated rates of HIV infection. However, our exploration of risk factors among SW-IDU demonstrated that drug use patterns and environmental factors, rather than sexual risks, may explain the elevated HIV incidence among SW-IDU locally. Our findings highlight the need for social and structural interventions, including increased access to harm reduction programs and addiction treatment. PMID- 26558726 TI - Mechanisms of bone disease in HIV and hepatitis C virus: impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease. AB - OBJECTIVE: Both HIV and hepatitis C virus (HCV) infections are associated with higher osteoporotic fracture risk. Increased bone turnover, liver fibrosis, tenofovir (TDF) use or hormonal imbalances are possible underlying mechanisms. DESIGN: This prospective, cross-sectional study assessed 298 male volunteers with either virologically suppressed HIV or untreated HCV mono-infections, HIV/HCV co infection and noninfected controls. METHODOLOGY: Study participants underwent bone mineral density (BMD) by dual-energy x-ray absorptiometry and measurement of bone turnover markers [BTM: C-telopeptide (CTX) and osteocalcin (OC)], insulin like growth factor-1 (IGF-1), the sex steroids testosterone (T) and estradiol (E2), and the aspartate aminotransferase-to-platelet ratio index (APRI). Impact of HIV and HCV status on BMD was evaluated in multivariate models adjusting for APRI score, BTM, TDF exposure, IGF-1, and sex steroids. RESULTS: HIV and HCV status independently predicted lower BMD, controlling for age, race, BMI, and smoking (P = 0.017 and P = 0.010, respectively), whereas APRI did not (P = 0.84). HIV was associated with increased bone resorption (CTX: P < 0.001) and formation (OC: P = 0.014), whereas HCV infection was not associated with CTX (P = 0.30) or OC (P = 0.36). TDF exposure was associated with lower BMD (P < 0.01). IGF-1 was significantly decreased in HCV and increased in HIV. Tumor necrosis factor-alpha (P = 0.98), IGF-1 (P = 0.80), bioavailable T (P = 0.45) and E2 (P = 0.27) were not associated with BMD and did not attenuate the impact of HIV or HCV on BMD. CONCLUSION: HIV and TDF exposure decrease BMD through increased bone turnover, although the lower BMD in HCV is not explained by a high turnover state. Neither virus' effect on BMD is likely mediated through increased inflammation, liver fibrosis, IGF-1, or sex steroids. PMID- 26558727 TI - High rate of lymphoma among a UK cohort of adolescents with vertically acquired HIV-1 infection transitioning to adult care in the era of antiretroviral therapy. AB - Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424-0.426). Previously described risk factors, including low nadir CD4 cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients. PMID- 26558728 TI - HIV mono-infection is associated with an impaired anti-hepatitis C virus activity of natural killer cells. AB - OBJECTIVE: Hepatitis C virus (HCV) infection in HIV(+) patients is associated with faster liver disease progression compared with HCV mono-infection. HIV associated immune defects are considered to play an important role in this context. Here, we analyzed the effects of HIV infection on natural killer (NK) cell-mediated anti-HCV activity. DESIGN: NK cell phenotype and interferon gamma (IFN-gamma) production, NK cell-mediated inhibition of HCV replication and CD4 T cell/NK cell interactions were studied in treatment naive HIV (n = 22), and HIV patients under combined antiretroviral therapy (n = 29), compared with healthy controls (n = 20). METHODS: NK cell-mediated inhibition of HCV replication was analyzed using the HuH7A2HCVreplicon model. IFN-gamma production of NK cells as well as interleukin-2 secretion of CD4 T lymphocytes were studied by flow cytometry. RESULTS: Peripheral blood mononuclear cells from HIV(+) patients displayed a significantly impaired anti-HCV activity, irrespective of combined antiretroviral therapy. This could in part be explained by HIV-associated decline in NK cell numbers. In addition, NK cell IFN-gamma production was significantly impaired in HIV infection. Accordingly, we found low frequency of IFN-gamma(+) NK cells in HIV(+) patients to be associated with ineffective inhibition of HCV replication. Finally, we show that CD4 T-cell-mediated stimulation of NK cell IFN gamma production was dysregulated in HIV infection with an impaired interleukin-2 response of NK cells. CONCLUSION: HIV infection has a strong suppressive effect on anti-HCV activity of NK cells. This may contribute to low spontaneous clearance rate and accelerated progression of HCV-associated liver disease observed in HIV(+) patients. PMID- 26558729 TI - Incidence of malaria by cotrimoxazole use in HIV-infected Ugandan adults on antiretroviral therapy: a randomised, placebo-controlled study. AB - INTRODUCTION: Previous unblinded trials have shown increased malaria among HIV infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV infected adults on ART in a double-blind, placebo-controlled trial. METHODS: HIV infected Ugandan adults stable on ART and CTX with CD4 cell count at least 250 cells/MUl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes. RESULTS: A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2-10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74-4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18-0.49). There was one malaria-related death (CTX arm). CONCLUSION: HIV-infected adults - who are stable on ART and stop prophylactic CTX - experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis. PMID- 26558722 TI - Is hardship during migration a determinant of HIV infection? Results from the ANRS PARCOURS study of sub-Saharan African migrants in France. AB - OBJECTIVES: In Europe, sub-Saharan African migrants are a key population for HIV infection. We analyse how social hardships during settlement in France shape sexual partnerships and HIV risk. DESIGN: PARCOURS is a life-event survey conducted in 2012-2013 in 74 health-care facilities in the Paris region, among three groups of sub-Saharan migrants: 926 receiving HIV care (296 acquired HIV in France), 779 with chronic hepatitis B, and 763 with neither HIV nor hepatitis B (reference group). METHODS: Hardships (lack of residence permit, economic resources and housing) and sexual partnerships were documented for each year since arrival in France. For each sex, reported sexual partnerships were compared by group and their associations with hardships each year analysed with mixed effects logistic regression models. RESULTS: Hardships were frequent: more than 40% had lived a year or longer without a residence permit, and more than 20% without stable housing. Most of the migrants had nonstable and concurrent partnerships, more frequent among those who acquired HIV in France compared with reference group, as were casual partnerships among men (76.7 vs. 54.2%; P = 0.004) and women (52.4 vs. 30.5%; P = 0.02), concurrent partnerships among men (69.9 vs. 45.8%; P = 0.02), and transactional partnerships among women (8.6 vs. 2.3%; P = 0.006). Hardship increased risky behaviours: in women, lacking a residence permit increased casual and transactional partnerships [resp. odds ratio (OR) = 2.01(1.48-2.72) and OR = 6.27(2.25-17.44)]. Same trends were observed for lacking stable housing [OR = 3.71(2.75-5.00) and OR = 10.58 (4.68 23.93)]. CONCLUSION: Hardships faced by migrants increase HIV risks. Women, especially during the period without stable housing, appear especially vulnerable. PMID- 26558730 TI - Distinct cytokine/chemokine network in semen and blood characterize different stages of HIV infection. AB - OBJECTIVE: The cytokine/chemokine network is used by the innate and adaptive immune system to orchestrate effective immune responses. Here, we describe the cross-sectional association between cytokine levels and stage of HIV infection to gain novel insights into HIV-1 immunopathogenesis and identify novel therapeutic targets. DESIGN: Concentrations of 31 cytokine/chemokines were retrospectively measured in blood and seminal plasma collected from 252 individuals enrolled in four well characterized cohorts: HIV-uninfected, untreated HIV-infected in early phase of infection, untreated HIV-infected in late phase of infection, and HIV infected on antiretroviral therapy with undetectable HIV RNA levels in blood (<50 copies/ml). METHODS: Cytokine/chemokine levels were measured by multiplex-bead array. Comparisons between groups were performed by Mann-Whitney U-test and P values were adjusted for multiple comparisons using the Benjamini-Hochberg method. RESULTS: Presence of HIV-infection skewed the cytokine/chemokine network towards a pro-inflammatory response in both blood and semen compared to HIV uninfected controls. Such changes emerged within the first weeks of infection and were maintained thereafter: Among untreated HIV-infected individuals, none of the 31 measured cytokines were significantly different between early and later stages of infection. Suppression of plasma HIV RNA with ART did not result in normalization of the levels of pro-inflammatory cytokines in blood. In semen, several pro-inflammatory cytokines were even further upregulated in ART-treated compared with HIV-uninfected and HIV-untreated individuals. CONCLUSION: A profound disruption in the cytokine/chemokine network is evident in blood and semen from the earliest stage of HIV infection shortly after the first detection of systemic viremia. These changes are maintained throughout the chronic phase of the infection and do not normalize despite ART and suppression of plasma HIV RNA. PMID- 26558731 TI - Serum oxidized low-density lipoprotein decreases in response to statin therapy and relates independently to reductions in coronary plaque in patients with HIV. AB - OBJECTIVE: Circulating oxidized low-density lipoprotein (oxLDL) levels are elevated in HIV-infected patients and have been associated with atherosclerosis. Statins have been shown to reduce plaque on coronary computed tomography angiography (cCTA) in HIV-infected individuals. Thus, we investigated the effect of statins on serum oxLDL levels and the relationship between changes in oxLDL and coronary atherosclerosis on cCTA in patients with HIV. DESIGN: We previously conducted a 12-month randomized, placebo-controlled trial with atorvastatin in 40 HIV-infected patients on stable antiretroviral therapy with subclinical coronary atherosclerosis and low-density lipoprotein (LDL)-cholesterol less than 130 mg/dl. METHODS: In the current analysis, patients underwent cCTA and measurements of serum oxLDL, sCD14, sCD163, lipoprotein phospholipase-A2, and fasting lipids at baseline and end of the study. RESULTS: Nineteen patients were randomized to atorvastatin and 21 patients to placebo. Serum oxLDL decreased -22.7% (95% CI 28.7 to -16.7) in the atorvastatin group and increased 7.5% (95% CI -3.3 to 18.4) in the placebo group (P < 0.0001). Change in oxLDL significantly correlated with changes in noncalcified plaque volume, total plaque volume, positively remodeled plaque, and low attenuation plaque. The association between changes in oxLDL and noncalcified plaque volume was independent of the baseline 10-year Framingham risk, LDL, CD4 cell count, and viral load. CONCLUSION: Statins lower oxLDL levels in HIV-infected patients, and reductions in oxLDL are related to improvements in coronary atherosclerosis, independent of traditional cardiovascular risk factors. Reductions in oxLDL may be one mechanism through which statins exert beneficial effects on reducing atherosclerosis in HIV-infected individuals. PMID- 26558732 TI - Factors associated with iohexol-based glomerular filtration rate slope over 36 months in HIV-negative and HIV-positive individuals. AB - BACKGROUND: Monitoring kidney function is important in HIV-positive persons, but creatinine-based estimates of glomerular filtration rate (GFR) have limitations. There are little to no data available assessing GFR trends in HIV-positive persons using a gold-standard measure of GFR. METHODS: We measured GFR based on iohexol plasma disappearance (iGFR) annually for 3 years in nondiabetic, HIV negative and HIV-positive volunteers with normal estimated kidney function. We used mixed linear models to evaluate factors associated with baseline iGFR and iGFR slope. RESULTS: One hundred HIV-negative and 191 HIV-positive, predominantly black individuals (median age 49 years) participated in the study and completed a total of 960 iGFR assessments over a median of 36 months. Despite similar estimated GFR at baseline, average iGFR values were lower in HIV-positive compared with HIV-negative participants (103.2 vs. 110.8, ml/min/1.73 m, P = 0.004). However, subsequent iGFR slope was not significantly different in HIV positive and HIV-negative participants. In the HIV-positive group, the presence of carotid plaque and hepatitis C virus coinfection were associated with significantly lower iGFR values at baseline. A nonsuppressed HIV RNA level at baseline was associated with a significantly more rapid iGFR decline compared with individuals with HIV RNA less than 400 copies/ml (-4.69 vs. -1.31 ml/min per 1.73 m per year, P = 0.005). Other factors significantly associated with iGFR slope included albuminuria and glycosylated hemoglobin. CONCLUSION: Compared with HIV-negative persons, HIV-positive participants had significantly lower baseline iGFR, despite similar estimated GFR in the two groups. Nonsuppressed HIV RNA at baseline was associated with a more rapid iGFR decline over 3 years. PMID- 26558733 TI - Cryptococcal antigen screening in HIV-infected adults: let's get straight to the point. PMID- 26558734 TI - Safety of rilpivirine and boceprevir coadministration in HIV-infected patients treated for acute hepatitis C virus infection. PMID- 26558736 TI - Medicare claims data reliably identify treatments for basal cell carcinoma and squamous cell carcinoma: a prospective cohort study. AB - OBJECTIVE: To investigate the accuracy of Medical Benefit Schedule (MBS) item numbers to identify treatments for basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). METHODS: We linked records from QSkin Study participants (n=37,103) to Medicare. We measured the proportion of Medicare claims for primary excision of BCC/SCC that had corresponding claims for histopathology services. In subsets of participants, we estimated the sensitivity and external concordance of MBS item numbers for identifying BCC/SCC diagnoses by comparing against 'gold standard' histopathology reports. RESULTS: A total of 2,821 (7.6%) participants had 4,830 separate Medicare claims for BCC/SCC excision; almost all (97%) had contemporaneous Medicare claims for histopathology services. Among participants with BCC/SCC confirmed by histology reports, 76% had a corresponding Medicare claim for primary surgical excision of BCC/SCC. External concordance for Medicare claims for primary BCC/SCC excision was 68%, increasing to 97% when diagnoses for intra-epidermal carcinomas and keratoacanthomas were included. CONCLUSIONS: MBS item numbers for primary excision of BCC/SCC are reasonably reliable for determining incident cases of keratinocyte skin cancers, but may underestimate incidence by up to 24%. IMPLICATIONS: Medicare claims data may have utility in monitoring trends in conditions for which there is no mandatory reporting. PMID- 26558737 TI - Cyano-Schmittel Cyclization through Base-Induced Propargyl-Allenyl Isomerization: Highly Modular Synthesis of Pyridine-Fused Aromatic Derivatives. AB - The cyano-Schmittel cyclization of in situ-generated cyano-allenes has been carried out. The DFT calculation results suggest that the diradical pathway plays a major role in this cyclization. The reactions can be conveniently performed in a one-pot manner through cascade Sonogashira coupling of terminal cyano-ynes with organic halides, followed by base-promoted propargyl-allenyl isomerization/cyclization, leading to an efficient access to pyridine-fused polycyclic architectures. In particular, a large variety of aryl or heteroaryl rings such as furans, thiophenes and pyridines can be incorporated into the follow-up cyano-Diels-Alder reactions, highlighting the great synthetic utility of this chemistry. PMID- 26558738 TI - Keto-benzo[h]-Coumarin-Based Near-Infrared Dyes with Large Stokes Shifts for Bioimaging Applications. AB - Fluorescence imaging is a promising tool for the visualization of biomolecules in living systems and there is great demand for new fluorescent dyes that absorb and emit in the near-infrared (NIR) region. Herein, we constructed three new fluorescent dyes (NBC dyes) based on keto-benzo[h]coumarin (k-BC) and benzopyrilium salts. These dyes showed large Stokes shifts (>100 nm) and NIR emission (>800 nm). The relationship between the structures and optical properties of these dyes was further investigated by using density functional theory calculations at the B3LYP/6-3G level of theory. Fluorescence images indicated that the fabricated dyes exhibited good photostability and low cytotoxicity and, thus, have potential applications as imaging agents in living cells and animals. PMID- 26558739 TI - Combined Global Longitudinal Strain and Intraventricular Mechanical Dyssynchrony Predicts Long-Term Outcome in Patients With Systolic Heart Failure. AB - BACKGROUND: Left ventricular (LV) ejection fraction (EF) and QRS duration enable prediction of outcome in patients with systolic heart failure (SHF). We assessed the predictive value of global longitudinal strain (GLS) and mechanical dyssynchrony for prognosis in SHF patients. METHODS AND RESULTS: Two-hundred and forty SHF patients with LVEF <=40% were studied. Global LV function and intraventricular mechanical dyssynchrony were calculated as GLS and SD of the time to peak longitudinal strain (SDepsilon) over 18 LV segments. The added value of GLS and SDepsilon for outcome prediction was assessed using nested Cox models. Sixty-six patients (28%) reached the study endpoint of all-cause mortality/heart transplantation over a median follow-up period of 45 months. Baseline variables associated with adverse outcome were age, glomerular filtration rate, pulmonary artery systolic pressure, diabetes and LV end-systolic volume (model chi(2)=69.8). The predictive power of the clinical variables was greater with addition of GLS (chi(2)=81.1) or SDepsilon (chi(2)=102.3) than with LVEF (chi(2)=73.9) or QRS duration (chi(2)=75.5; both P<0.005). GLS (HR, 1.88; P=0.03) and SDepsilon (HR, 1.48; P=0.04) were independent predictors after adjustment for the baseline variables. Patients with impaired GLS (>=-7.8%) and mechanical dyssynchrony (SDepsilon >=72 ms) had poor outcome. CONCLUSIONS: Combined assessment of global LV function and mechanical dyssynchrony using speckle tracking strain enabled the prediction of long-term outcome in SHF patients. PMID- 26558740 TI - Reliability of the Abbreviated Westmead Post-traumatic Amnesia Scale in children: Impact of age on test results. AB - OBJECTIVE: This study aimed to determine the reliability of the Abbreviated Westmead Post-traumatic Amnesia Scale (A-WPTAS) in children by examining the impact of age on A-WPTAS performance. METHODS: Participants were typically developing patients with minor illnesses or injuries and/or accompanying siblings aged 5-10 years, attending a children's hospital ED. Exclusion criteria included: (i) a recent traumatic brain injury; (ii) developmental disability; (iii) recent drug administration judged to impact cognition; and/or (iv) non-English speaking background. The A-WPTAS was administered on two occasions separated by approximately 60 min. Logistic regression was used to determine the odds of passing based on age. RESULTS: A total of 125 children completed the A-WPTAS assessments. A-WPTAS pass rates were 36% for 5 year olds, 68% for 6 year olds, and exceeded 90% for 7-10 year olds. Compared with 9 year olds, 5 year olds had significantly lower odds of passing (P = 0.003), a trend that persisted for 6 year olds (P = 0.052). Among 5 and 6 year olds, failure was predominantly due to difficulty with temporo-spatial orientation items. CONCLUSIONS: The A-WPTAS is reliable for use in children aged 7 years and older, while its use in children aged 6 years and under results in an unsatisfactory high false positive rate, limiting its clinical utility. The adult-level performance of children aged 7 years onwards provides strong support for using the tool in the early management of these children with mild traumatic brain injury in Australian EDs. PMID- 26558742 TI - Editor's note. PMID- 26558741 TI - Anastomotic leakage after colon cancer resection: does the individual surgeon matter? AB - AIM: Anastomotic leakage is one of the most feared complications after colonic resection. Many risk factors for anastomotic leakage have been reported, but the impact of an individual surgeon as a risk factor has scarcely been reported. The aim of this study was to assess if the individual surgeon is an independent risk factor for anastomotic leakage in colonic cancer surgery. METHOD: This was a retrospective analysis of prospectively collected data from patients who underwent elective resection for colon cancer with anastomosis at a specialized colorectal unit from January 1993 to December 2010. Anastomotic leaks were diagnosed according to standardized criteria. Patient and tumour characteristics, surgical procedure and operating surgeons were analysed. A logistic regression model was used to discriminate statistical variation and identify risk factors for anastomotic leakage. RESULTS: A total of 1045 patients underwent elective colon cancer resection with primary anastomosis. Anastomotic leakage occurred in 6.4% of patients. Ileocolic anastomosis had an anastomotic leakage rate of 7.2%, colo-colonic/colorectal anastomosis 5.2% and ileorectal anastomosis 12.7%, with intersurgeon variability. The independent risk factors associated with anastomotic leakage were the use of perioperative blood transfusion (OR 2.83, CI 1.59-5.06, P < 0.0001) and the individual surgeon performing the procedure (OR up to 8.44, P < 0.0001). CONCLUSION: In addition to perioperative blood transfusion, the individual surgeon was identified as an important risk factor for anastomotic leakage. Efforts should be made to reduce performance variability amongst surgeons. PMID- 26558743 TI - Studying an unreal world: incentives on Internet-based interventions for alcohol use. PMID- 26558744 TI - Diastereoselective Synthesis of Protected 1,3-Diols by Catalytic Diol Relocation. AB - A complementary diastereoselective gold(I) or bismuth(III) catalyzed tandem hemiacetalization/dehydrative cyclization of 1,5-monoallylic diols was developed to access 1,3-dioxolanes and dioxanes. This methodology provides rapid access to protected 1,3-diols under mild conditions with high levels of diastereoselectivity. PMID- 26558745 TI - Taxanes-induced cutaneous eruption: another histopathologic mimicker of malignancy. AB - BACKGROUND: Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation. OBJECTIVES: We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically. METHODS: Cutaneous biopsies were obtained in each patient. RESULTS: Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case. DISCUSSION: These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported. CONCLUSION: Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes. PMID- 26558746 TI - F1 -ATP synthase alpha-subunit: a potential target for RNAi-mediated pest management of Locusta migratoria manilensis. AB - BACKGROUND: The migratory locust is one of the most destructive agricultural pests worldwide. ATP synthase (F0 F1 -ATPase) uses proton or sodium motive force to produce 90% of the cellular ATP, and the alpha-subunit of F1 -ATP synthase (ATP5A) is vital for F1 -ATP synthase. Here, we tested whether ATP5A could be a potential target for RNAi-mediated pest management of L. migratoria. RESULTS: Lm ATP5A was cloned and characterised. Lm-ATP5A is expressed in all tissues. Injection of 100 ng of the double-stranded RNA of ATP5A (dsATP5A) knocked down the transcription of the target gene and caused mortality in 1.5-5 days. The Lm ATP5A protein level, the oligomycin-sensitive ATP synthetic and hydrolytic activities and the ATP content were correspondingly reduced following dsATP5A injection. CONCLUSION: These findings demonstrated the essential roles of Lm ATP5A in L. migratoria and identified it as a potential target for insect pest control. (c) 2015 Society of Chemical Industry. PMID- 26558747 TI - Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course. AB - Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking. PMID- 26558748 TI - Bottom-Up Proteomics (2013-2015): Keeping up in the Era of Systems Biology. PMID- 26558749 TI - A comparison between porcine, ovine, and bovine intervertebral disc anatomy and single lamella annulus fibrosus tensile properties. AB - This project aimed to compare gross anatomical measures and biomechanical properties of single lamellae from the annulus fibrosus of ovine and porcine lumbar vertebrae, and bovine tail vertebrae. The morphology of the vertebrae of these species differ significantly both from each other and from human, yet how these differences alter biomechanical properties is unknown. Geometric parameters measured in this study included: 1) absolute and relative intervertebral (IVD) and vertebral body height and 2) absolute and relative intervertebral disc (IVD) anterior-posterior (AP) and medial-lateral (ML) widths. Single lamella tensile properties included toe-region stress and stretch ratio, stiffness, and tensile strength. As expected, the bovine tail IVD revealed a more circular shape compared with both the ovine and porcine lumbar IVD. The bovine tail also had the largest IVD to vertebral body height ratio (due to having the highest absolute IVD height). Bovine tail lamellae were also found to be strongest and stiffest (in tension) while ovine lumbar lamellae were weakest and most compliant. Histological analysis revealed the greatest proportion of collagen in the bovine corroborating findings of increased strength and stiffness. The observed differences in anatomical shape, connective tissue composition, and tensile properties need to be considered when choosing an appropriate model for IVD research. PMID- 26558750 TI - AC Electrothermal Circulatory Pumping Chip for Cell Culture. AB - Herein we describe a novel AC electrothermal (ACET) fluidic circulatory pumping chip to overcome the challenge of fluid-to-tissue ratio for "human-on-a-chip" cell culture systems. To avoid the deleterious effects of Joule heating and electric current on sample cells, a rectangular microchannel was designed with distantly separated regions for pumping and cell culture. Temperature variations were examined using a commercial thermocouple sensor to detect temperature values in both pumping and culture regions. To generate a sufficient ACET circulatory pumping rate, 30 pairs of asymmetrical electrodes were employed in the pumping region; generated ACET velocity was measured by fluorescent microparticle image velocimetry. The benefits of our pumping chip were demonstrated by culturing human embryonic kidney cells (HEK293T) and human colon carcinoma cells (SW620) for 72 h with an energized voltage of 3 V and 10 MHz. Cells grew and proliferated well, implying our ACET circulatory pumping chip has great potential for cell culture and tissue engineering applications. PMID- 26558751 TI - Oxidative Coupling between Two Hydrocarbons: An Update of Recent C-H Functionalizations. PMID- 26558752 TI - Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies. AB - INTRODUCTION: Neurodevelopmental disorders (NDDs) are common and severely debilitating. Their chronic nature and reliance on both genetic and environmental factors makes studying NDDs and their treatment a challenging task. AREAS COVERED: Herein, the authors discuss the neurobiological mechanisms of NDDs, and present recommendations on their translational research and therapy, outlined by the International Stress and Behavior Society. Various drugs currently prescribed to treat NDDs also represent a highly diverse group. Acting on various neurotransmitter and physiological systems, these drugs often lack specificity of action, and are commonly used to treat multiple other psychiatric conditions. There has also been relatively little progress in the development of novel medications to treat NDDs. Based on clinical, preclinical and translational models of NDDs, our recommendations cover a wide range of methodological approaches and conceptual strategies. EXPERT OPINION: To improve pharmacotherapy and drug discovery for NDDs, we need a stronger emphasis on targeting multiple endophenotypes, a better dissection of genetic/epigenetic factors or "hidden heritability," and a careful consideration of potential developmental/trophic roles of brain neurotransmitters. The validity of animal NDD models can be improved through discovery of novel (behavioral, physiological and neuroimaging) biomarkers, applying proper environmental enrichment, widening the spectrum of model organisms, targeting developmental trajectories of NDD-related behaviors and comorbid conditions beyond traditional NDDs. While these recommendations cannot be addressed all in once, our increased understanding of NDD pathobiology may trigger innovative cross-disciplinary research expanding beyond traditional methods and concepts. PMID- 26558753 TI - Clinically Relevant Growth Conditions Alter Acinetobacter baumannii Antibiotic Susceptibility and Promote Identification of Novel Antibacterial Agents. AB - Biological processes that govern bacterial proliferation and survival in the host environment(s) are likely to be vastly different from those that are required for viability in nutrient-rich laboratory media. Consequently, growth-based antimicrobial screens performed in conditions modeling aspects of bacterial disease states have the potential to identify new classes of antimicrobials that would be missed by screens performed in conventional laboratory media. Accordingly, we performed screens of the Selleck library of 853 FDA approved drugs for agents that exhibit antimicrobial activity toward the Gram-negative bacterial pathogen Acinetobacter baumannii during growth in human serum, lung surfactant, and/or the organism in the biofilm state and compared those results to that of conventional laboratory medium. Results revealed that a total of 90 compounds representing 73 antibiotics and 17 agents that were developed for alternative therapeutic indications displayed antimicrobial properties toward the test strain in at least one screening condition. Of the active library antibiotics only four agents, rifampin, rifaximin, ciprofloxacin and tetracycline, exhibited antimicrobial activity toward the organism during all screening conditions, whereas the remainder were inactive in >= 1 condition; 56 antibiotics were inactive during serum growth, 25 and 38 were inactive toward lung surfactant grown and biofilm-associated cells, respectively, suggesting that subsets of antibiotics may outperform others in differing infection settings. Moreover, 9 antibiotics that are predominantly used for the treatment Gram positive pathogens and 10 non-antibiotics lacked detectable antimicrobial activity toward A. baumannii grown in conventional medium but were active during >= 1 alternative growth condition(s). Such agents may represent promising anti Acinetobacter agents that would have likely been overlooked by antimicrobial whole cell screening assays performed in traditional laboratory screening media. PMID- 26558754 TI - Common Visual Preference for Curved Contours in Humans and Great Apes. AB - Among the visual preferences that guide many everyday activities and decisions, from consumer choices to social judgment, preference for curved over sharp-angled contours is commonly thought to have played an adaptive role throughout human evolution, favoring the avoidance of potentially harmful objects. However, because nonhuman primates also exhibit preferences for certain visual qualities, it is conceivable that humans' preference for curved contours is grounded on perceptual and cognitive mechanisms shared with extant nonhuman primate species. Here we aimed to determine whether nonhuman great apes and humans share a visual preference for curved over sharp-angled contours using a 2-alternative forced choice experimental paradigm under comparable conditions. Our results revealed that the human group and the great ape group indeed share a common preference for curved over sharp-angled contours, but that they differ in the manner and magnitude with which this preference is expressed behaviorally. These results suggest that humans' visual preference for curved objects evolved from earlier primate species' visual preferences, and that during this process it became stronger, but also more susceptible to the influence of higher cognitive processes and preference for other visual features. PMID- 26558755 TI - Gene Network Rewiring to Study Melanoma Stage Progression and Elements Essential for Driving Melanoma. AB - Metastatic melanoma patients have a poor prognosis, mainly attributable to the underlying heterogeneity in melanoma driver genes and altered gene expression profiles. These characteristics of melanoma also make the development of drugs and identification of novel drug targets for metastatic melanoma a daunting task. Systems biology offers an alternative approach to re-explore the genes or gene sets that display dysregulated behaviour without being differentially expressed. In this study, we have performed systems biology studies to enhance our knowledge about the conserved property of disease genes or gene sets among mutually exclusive datasets representing melanoma progression. We meta-analysed 642 microarray samples to generate melanoma reconstructed networks representing four different stages of melanoma progression to extract genes with altered molecular circuitry wiring as compared to a normal cellular state. Intriguingly, a majority of the melanoma network-rewired genes are not differentially expressed and the disease genes involved in melanoma progression consistently modulate its activity by rewiring network connections. We found that the shortlisted disease genes in the study show strong and abnormal network connectivity, which enhances with the disease progression. Moreover, the deviated network properties of the disease gene sets allow ranking/prioritization of different enriched, dysregulated and conserved pathway terms in metastatic melanoma, in agreement with previous findings. Our analysis also reveals presence of distinct network hubs in different stages of metastasizing tumor for the same set of pathways in the statistically conserved gene sets. The study results are also presented as a freely available database at http://bioinfo.icgeb.res.in/m3db/. The web-based database resource consists of results from the analysis presented here, integrated with cytoscape web and user-friendly tools for visualization, retrieval and further analysis. PMID- 26558756 TI - A Retrospective Longitudinal Within-Subject Risk Interval Analysis of Immunoglobulin Treatment for Recurrent Acute Exacerbation of Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Recurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, debilitating, costly and often difficult to prevent. METHODS: We reviewed records of patients who had COPD and immunoglobulin (Ig) treatment as adjunctive preventative treatment for AECOPD, and documented all AECOPD episodes for one year before and after initiation of Ig treatment. We graded AECOPD episodes as moderate for prescription of antibiotics and/or corticosteroids or for visit to the Emergency Department, and as severe for hospital admission. We conducted a retrospective within-subject self-controlled risk interval analysis to compare the outcome of annual AECOPD rate before and after treatment. RESULTS: We identified 22 cases of certain COPD, of which three had early discontinuation of Ig treatment due to rash and local swelling to subcutaneous Ig, and five had incomplete records leaving 14 cases for analyses. The median baseline IgG level was 5.9 g/L (interquartile range 4.1-7.4). Eight had CT radiographic bronchiectasis. Overall, the incidence of AECOPD was consistently and significantly reduced in frequency from mean 4.7 (+/- 3.1) per patient-year before, to 0.6 (+/- 1.0) after the Ig treatment (p = 0.0001). There were twelve episodes of severe AECOPD (in seven cases) in the year prior, and one in the year after Ig treatment initiation (p = 0.016). CONCLUSIONS: Ig treatment appears to decrease the frequency of moderate and severe recurrent AECOPD. A prospective, controlled evaluation of adjunctive Ig treatment to standard therapy of recurrent AECOPD is warranted. PMID- 26558757 TI - The Distribution of Coumarins and Furanocoumarins in Citrus Species Closely Matches Citrus Phylogeny and Reflects the Organization of Biosynthetic Pathways. AB - Citrus plants are able to produce defense compounds such as coumarins and furanocoumarins to cope with herbivorous insects and pathogens. In humans, these chemical compounds are strong photosensitizers and can interact with medications, leading to the "grapefruit juice effect". Removing coumarins and furanocoumarins from food and cosmetics imply additional costs and might alter product quality. Thus, the selection of Citrus cultivars displaying low coumarin and furanocoumarin contents constitutes a valuable alternative. In this study, we performed ultra-performance liquid chromatography coupled with mass spectrometry analyses to determine the contents of these compounds within the peel and the pulp of 61 Citrus species representative of the genetic diversity all Citrus. Generally, Citrus peel contains larger diversity and higher concentrations of coumarin/furanocoumarin than the pulp of the same fruits. According to the chemotypes found in the peel, Citrus species can be separated into 4 groups that correspond to the 4 ancestral taxa (pummelos, mandarins, citrons and papedas) and extended with their respective secondary species descendants. Three of the 4 ancestral taxa (pummelos, citrons and papedas) synthesize high amounts of these compounds, whereas mandarins appear practically devoid of them. Additionally, all ancestral taxa and their hybrids are logically organized according to the coumarin and furanocoumarin pathways described in the literature. This organization allows hypotheses to be drawn regarding the biosynthetic origin of compounds for which the biogenesis remains unresolved. Determining coumarin and furanocoumarin contents is also helpful for hypothesizing the origin of Citrus species for which the phylogeny is presently not firmly established. Finally, this work also notes favorable hybridization schemes that will lead to low coumarin and furanocoumarin contents, and we propose to select mandarins and Ichang papeda as Citrus varieties for use in creating species devoid of these toxic compounds in future breeding programs. PMID- 26558758 TI - Interpreting confidence intervals: A comment on Hoekstra, Morey, Rouder, and Wagenmakers (2014). AB - Hoekstra, Morey, Rouder, and Wagenmakers (Psychonomic Bulletin & Review 21(5), 1157-1164 2014) reported the results of a questionnaire designed to assess students' and researchers' understanding of confidence intervals (CIs). They interpreted their results as evidence that these groups "have no reliable knowledge about the correct interpretation of CIs" (Hoekstra et al. Psychonomic Bulletin & Review 21(5), 1157-1164 2014, p. 1161). We argue that their data do not substantiate this conclusion and that their report includes misleading suggestions about the correct interpretations of confidence intervals. PMID- 26558760 TI - Forensic examination of electrical tapes using high resolution magic angle spinning 1H NMR spectroscopy. AB - The application of high resolution magic angle spinning (HR-MAS) (1)H NMR spectroscopy is ideally suited for the differentiation of plastics. In addition to the actual material composition, the different types of polymer architectures and tacticity provide characteristic signals in the fingerprint of the (1)H NMR spectra. The method facilitates forensic comparison, as even small amounts of insoluble but swellable plastic particles are utilized. The performance of HR-MAS NMR can be verified against other methods that were recently addressed in various articles about forensic tape comparison. In this study samples of the 90 electrical tapes already referenced by the FBI laboratory were used. The discrimination power of HR-MAS is demonstrated by the fact that more tape groups can be distinguished by NMR spectroscopy than by using the combined evaluation of several commonly used analytical techniques. An additional advantage of this robust and quick method is the very simple sample preparation. PMID- 26558759 TI - 1H-NMR-Based Metabolomic Study for Identifying Serum Profiles Associated with the Response to Etanercept in Patients with Rheumatoid Arthritis. AB - OBJECTIVE: A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients. METHODS: Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months' follow-up. Each patient was evaluated by the same rheumatologist before and after six months of treatment. At this time, the clinical response (good, moderate, none) was determined according to the EUropean League Against Rheumatism (EULAR) criteria, based on both erythrocyte sedimentation rate (EULAR-ESR) and C-reactive protein (EULAR-CRP). Sera collected prior and after six months of etanercept were analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate data analysis. RESULTS: Twenty-seven patients were enrolled: 18 had a good/moderate response and 9 were non responders according to both EULAR-ESR and EULAR-CRP after six months of etanercept. Metabolomic analysis at baseline was able to discriminate good, moderate, and non-responders with a very good predictivity (Q2 = 0.68) and an excellent sensitivity, specificity, and accuracy (100%). In good responders, we found an increase in isoleucine, leucine, valine, alanine, glutamine, tyrosine, and glucose levels and a decrease in 3 hydroxybutyrate levels after six months of treatment with etanercept with respect to baseline. CONCLUSION: Our study confirms the potential of metabolomic analysis to predict the response to biological agents. Changes in metabolic profiles during treatment may help elucidate their mechanism of action. PMID- 26558761 TI - A novel method for the determination of three volatile organic compounds in exhaled breath by solid-phase microextraction-ion mobility spectrometry. AB - A method was carried out for the quantitative determination of the concentrations of volatile organic compounds (VOCs) using solid-phase microextraction and ion mobility spectrometry (SPME-IMS). This method was optimized and evaluated. The best results were obtained at sorption temperature 70 degrees C, desorption temperature 200 degrees C, and extraction time 15 min. Under the optimized conditions, the linear dynamic range was found to be 0.01-4.0 ppb (R(2) > 0.995), 2.3-400 ppm (R(2) > 0.994), and 2.5-76 ppb (R(2) > 0.998) for acetone, acetaldehyde, and acetonitrile, respectively. The detection limits for acetone, acetaldehyde, and acetonitrile were 0.001 ppb, 0.18 ppm, and 0.22 ppb, respectively. As a practical application, the method was applied for the determination of acetone, acetaldehyde, and acetonitrile in human breath matrix. Therefore, the proposed method was found to be effective and simple enough to be strongly recommended for real sample analysis. PMID- 26558762 TI - Surface plasmon resonance for the label-free detection of Alzheimer's beta amyloid peptide aggregation. AB - Amyloid peptide oligomers and fibrils are studied as targets for therapy and diagnosis of Alzheimer's disease. They are usually detected by amyloid incubation, but such method is necessarily associated with Abeta1-42 depletion and dye binding or conjugation, which have a complex influence on fibril growth, provide information about fibril elongation over long time periods only, and might lead to false-positive results in amyloid inhibition assay. Surface plasmon resonance (SPR) is used to study with no labelling and in real time the aggregation of Abeta1-42 amyloid on specific antibodies. SPR data show, for the first time by using SPR, a multi-phase association behavior for Abeta1-42 oligomers accounting for a sigmoidal growth of amyloid as a function of time, with two antibody-dependent aggregation patterns. The new method represents an advantageous alternative to traditional procedures for investigating amyloid self assembly and inhibition from early-stage oligomer association, on the time scale of seconds to minutes, to long-term polymerization, on the time scale of hours to days. PMID- 26558763 TI - Metabolic profile of salidroside in rats using high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. AB - A high-performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR MS) method was developed to study the in vivo metabolism of salidroside for the first time. Plasma, urine, bile, and feces samples were collected from male rats after a single intragastric gavage of salidroside at a dose of 50 mg/kg. Besides the parent drug, a total of seven metabolites (three phase I and four phase II metabolites) were detected and tentatively identified by comparing their mass spectrometry profiles with those of salidroside. Results indicated that metabolic pathways of salidroside in male rats included hydroxylation, dehydrogenation, glucuronidation, and sulfate conjugation. Among them, glucuronidation and sulfate conjugation were the major metabolic reactions. And most important, the detection of the sulfation metabolite of p-tyrosol provides a clue for whether the deglycosylation of salidroside occurs in vivo after intragastric gavage. In summary, results obtained in this study may contribute to the better understanding of the safety and mechanism of action of salidroside. PMID- 26558764 TI - Factors Affecting Time to Sputum Culture Conversion in Adults with Pulmonary Tuberculosis: A Historical Cohort Study without Censored Cases. AB - BACKGROUND: In patients with pulmonary tuberculosis (TB), shortening the time to sputum culture conversion is desirable to reduce the likelihood of mycobacterial transmission. A persistent positive sputum culture after 2 months of treatment is reported to be associated with the presence of cavitation and the extent of disease on chest X-ray, high colony count, diabetes mellitus, and smoking. However, little is known about factors affecting the time to sputum culture conversion. This study was conducted to evaluate factors affecting the time to sputum culture conversion throughout the course of treatment in adults with pulmonary TB. METHODS: This study was performed using a database of the medical records of patients with active pulmonary TB who were treated at Hirakata Kohsai Hospital in Hirakata City, Osaka, Japan, from October 2000 to October 2002. Cox proportional-hazards analysis was used to evaluate factors affecting the time to sputum culture conversion after adjusting for potential confounders. RESULTS: The data of 86 patients with pulmonary TB were analyzed. The median time to sputum culture conversion was 39 days, and the maximum time was 116 days. The Cox proportional-hazards analysis showed that a higher smear grading (HR, 0.40; 95%CI, 0.23-0.71) and a history of ever smoking (HR, 0.48; 95%CI, 0.25-0.94) were associated with delayed sputum culture conversion. CONCLUSION: High smear grading and smoking prolonged the time to sputum culture conversion in adults with pulmonary TB. To effectively control TB, measures to decrease the cigarette smoking rate should be implemented, in addition to early detection and timely anti-TB treatment. PMID- 26558765 TI - Obsessive-Compulsive Disorder and Autism Spectrum Disorders: Longitudinal and Offspring Risk. AB - BACKGROUND: Despite substantial similarities and overlaps in the pathophysiology of obsessive-compulsive disorders (OCD) and autism spectrum disorders, little is known about the clinical and etiologic cohesion of these two disorders. We therefore aimed to determine the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. METHODS: In a prospective study design we explored the effect of a prior diagnosis of OCD in patients and parents on the susceptibility to autism spectrum disorders and vice versa. Analyses were adjusted for sex, age, calendar year, parental age and place at residence at time of birth. As measures of relative risk incidence rate ratios (IRR) and accompanying 95% confidence intervals (CIs) were employed. RESULTS: The risk of a comorbid diagnosis of OCD in individuals with autism spectrum disorder and aggregation of autism spectrum disorders in offspring of parents with OCD were increased. Individuals first diagnosed with autism spectrum disorders had a 2 fold higher risk of a later diagnosis of OCD (IRR = 2.18, 95% CI = 1.91-2.48), whereas individuals diagnosed with OCD displayed a nearly 4-fold higher risk to be diagnosed with autism spectrum disorders (IRR = 3.91, 95% CI = 3.46-4.40) later in life. The observed associations were somewhat stronger for less severe types of autism spectrum disorders without a comorbid diagnosis of mental disabilities. CONCLUSIONS: The high comorbidity, sequential risk, and shared familial risks between OCD and autism spectrum disorders are suggestive of partially shared etiological mechanisms. The results have implications for current gene-searching efforts and for clinical practice. PMID- 26558767 TI - Synthesis of vanillic acid using whole cell nitrilase of wild and mutant Gordonia terrae. AB - The resting cells of Gordonia terrae mutant E9 having enhanced nitrilase activity were used for biotransformation of 4-hydroxy-3-methoxybenzonitrile into vanillic acid. The maximum conversion was observed in 0.1 M phosphate buffer (pH 8.0), using 60 mM substrate and 0.75 mgDCW resting cells in 1 mL reaction at 40 degrees C. Km of the whole cell nitrilase of wild and mutant strains of G. terrae for this substrate were 20 and 16.6 mM, and Vmax were 0.19 and 0.95 Umg(-1)(DCW), respectively. Fed batch reaction for transformation of 4-hydroxy-3 methoxybenzonitrile using whole cell nitrilase of wild G. terrae resulted in 2.36 g of vanillic acid in 5 h with a catalytic and volumetric productivity of 0.78 gg(-1)(DCW) h(-1) and 4.72 gL(-1)h(-1), respectively. The whole cell nitrilase of G. terrae mutant E9 resulted in higher catalytic and volumetric productivity, i.e., 1.68 gg(-1)DCW h(-1) and 10 gL(-1)h(-1). A total 5.04 g of vanillic acid with 99% purity were accumulated in 100 mL of reaction after 5 h. PMID- 26558766 TI - Plasma vitamin D biomarkers and leukocyte telomere length in men. AB - PURPOSE: Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In women, higher plasma 25-hydroxyvitamin D (25(OH)D) has been shown to be associated with longer telomere length, but the relationship has not been assessed in men. METHODS: We conducted a cross sectional analysis of 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D) and relative leukocyte telomere length (LTL) among 2483 men [1832 men for 1,25(OH)2D] who were selected as cases and controls in three studies of telomeres and cancer nested within the Health Professionals Follow-up Study. We also genotyped 95 SNPs representing common genetic variation in vitamin D pathway genes. LTL was measured by quantitative PCR, and z-scores within each study were calculated. Associations were assessed by linear as well as logistic regression adjusting for age and other potential confounders. RESULTS: Age (P-trend < 0.0001), pack-years of smoking (P-trend = 0.04) and body mass index (P-trend = 0.05) were inversely associated with LTL. Neither 25(OH)D nor 1,25(OH)2D was associated with LTL (multivariable-adjusted P-trend 0.69 and 0.41, respectively, for the linear regression model). One SNP in the retinoid X receptor alpha gene was associated with long LTL (P = 0.0003). CONCLUSIONS: In this cross-sectional study of men, 25(OH)D and 1,25(OH)2D were not associated with relative LTL. PMID- 26558768 TI - Stimulation with bone morphogenetic protein-2 (BMP-2) enhances bone-tendon integration in vitro. AB - PURPOSE: Preclinical studies have reported that bone morphogenetic protein (BMP) 2 promotes bone-tendon healing following anterior cruciate ligament reconstruction. We examined the region-specific effects of BMP-2 on osteoblast and fibroblast differentiation in a highly standardized murine in vitro co culture model of bone-tendon integration. MATERIALS AND METHODS: We used quantitative PCR to measure the dose- and time-dependent influence of BMP-2 on the expression of alkaline phosphatase, osteocalcin, collagen type 1 (alpha 1 chain), runt-related transcription factor 2, osteopontin, collagen type 1 (alpha 2 chain), collagen type 5 (alpha 1 chain), decorin, fibromodulin, mohawk homeobox, bone morphogenetic protein receptor, type 1A, bone morphogenetic protein receptor, type 2, and Noggin in the osteoblast, interface, and fibroblast regions of a co-culture model of the murine preosteoblast cell line MC3T3-E1 and the fibroblast cell line 3T6. RESULTS: Stimulation with BMP-2 resulted in a significant upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), collagens (p < 0.001), runt-related transcription factor 2 (p < 0.05), and osteopontin (p < 0.001) expression in the osteoblast region. In the interface region, BMP-2 exposure led to dose- and time-dependent upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), osteopontin (p < 0.001), runt related transcription factor 2 (p < 0.001), and markers of extracellular matrix production (p < 0.001). Both BMP receptors showed a significant BMP-2-dependent upregulation at the interface region, and Noggin was downregulated at the osteoblast and interface region following BMP-2 exposure. CONCLUSIONS: Exposure to BMP-2 upregulated the expression of genes associated with bone-tendon integration in vitro, suggesting the stimulation of transdifferentiation processes at the interface and fibroblast regions as well as the induction of positive feedback mechanisms. Further studies will be needed to establish BMP-2 dose and treatment algorithms following tendon reinsertion and reconstruction. PMID- 26558769 TI - GIRK Channels Mediate the Nonphotic Effects of Exogenous Melatonin. AB - Melatonin supplementation has been used as a therapeutic agent for several diseases, yet little is known about the underlying mechanisms by which melatonin synchronizes circadian rhythms. G-protein signaling plays a large role in melatonin-induced phase shifts of locomotor behavior and melatonin receptors activate G-protein-coupled inwardly rectifying potassium (GIRK) channels in Xenopus oocytes. The present study tested the hypothesis that melatonin influences circadian phase and electrical activity within the central clock in the suprachiasmatic nucleus (SCN) through GIRK channel activation. Unlike wild type littermates, GIRK2 knock-out (KO) mice failed to phase advance wheel-running behavior in response to 3 d subcutaneous injections of melatonin in the late day. Moreover, in vitro phase resetting of the SCN circadian clock by melatonin was blocked by coadministration of a GIRK channel antagonist tertiapin-q (TPQ). Loose patch electrophysiological recordings of SCN neurons revealed a significant reduction in the average action potential rate in response to melatonin. This effect was lost in SCN slices treated with TPQ and SCN slices from GIRK2 KO mice. The melatonin-induced suppression of firing rate corresponded with an increased inward current that was blocked by TPQ. Finally, application of ramelteon, a potent melatonin receptor agonist, significantly decreased firing rate and increased inward current within SCN neurons in a GIRK-dependent manner. These results are the first to show that GIRK channels are necessary for the effects of melatonin and ramelteon within the SCN. This study suggests that GIRK channels may be an alternative therapeutic target for diseases with evidence of circadian disruption, including aberrant melatonin signaling. SIGNIFICANCE STATEMENT: Despite the widespread use of melatonin supplementation for the treatment of sleep disruption and other neurological diseases such as epilepsy and depression, no studies have elucidated the molecular mechanisms linking melatonin-induced changes in neuronal activity to its therapeutic effects. Here, we used behavioral and electrophysiological techniques to address this scientific gap. Our results show that melatonin and ramelteon, a potent and clinically relevant melatonin receptor agonist, significantly affect the neurophysiological function of suprachiasmatic nucleus neurons through activation of G-protein-coupled inwardly rectifying potassium (GIRK) channels. Given the importance of GIRK channels for neuronal excitability (with >600 publications on these channels to date), our study should generate broad interest from neuroscientists in fields such as epilepsy, addiction, and cognition. PMID- 26558770 TI - Dopamine/Tyrosine Hydroxylase Neurons of the Hypothalamic Arcuate Nucleus Release GABA, Communicate with Dopaminergic and Other Arcuate Neurons, and Respond to Dynorphin, Met-Enkephalin, and Oxytocin. AB - We employ transgenic mice with selective expression of tdTomato or cre recombinase together with optogenetics to investigate whether hypothalamic arcuate (ARC) dopamine/tyrosine hydroxylase (TH) neurons interact with other ARC neurons, how they respond to hypothalamic neuropeptides, and to test whether these cells constitute a single homogeneous population. Immunostaining with dopamine and TH antisera was used to corroborate targeted transgene expression. Using whole-cell recording on a large number of neurons (n = 483), two types of neurons with different electrophysiological properties were identified in the dorsomedial ARC where 94% of TH neurons contained immunoreactive dopamine: bursting and nonbursting neurons. In contrast to rat, the regular oscillations of mouse bursting neurons depend on a mechanism involving both T-type calcium and A type potassium channel activation, but are independent of gap junction coupling. Optogenetic stimulation using cre recombinase-dependent ChIEF-AAV-DJ expressed in ARC TH neurons evoked postsynaptic GABA currents in the majority of neighboring dopamine and nondopamine neurons, suggesting for the first time substantial synaptic projections from ARC TH cells to other ARC neurons. Numerous met enkephalin (mENK) and dynorphin-immunoreactive boutons appeared to contact ARC TH neurons. mENK inhibited both types of TH neuron through G-protein coupled inwardly rectifying potassium currents mediated by delta and MU opioid receptors. Dynorphin-A inhibited both bursting and nonbursting TH neurons by activating kappa receptors. Oxytocin excited both bursting and nonbursting neurons. These results reveal a complexity of TH neurons that communicate extensively with neurons within the ARC. SIGNIFICANCE STATEMENT: Here, we show that the great majority of mouse hypothalamic arcuate nucleus (ARC) neurons that synthesize TH in the dorsomedial ARC also contain immunoreactive dopamine, and show either bursting or nonbursting electrical activity. Unlike rats, the mechanism underlying bursting was not dependent on gap junctions but required T-type calcium and A-type potassium channel activation. Neuropeptides dynorphin and met enkephalin inhibited dopamine neurons, whereas oxytocin excited them. Most ventrolateral ARC TH cells did not contain dopamine and did not show bursting electrical activity. TH-containing neurons appeared to release synaptic GABA within the ARC onto dopamine neurons and unidentified neurons, suggesting that the cells not only control pituitary hormones but also may modulate nearby neurons. PMID- 26558771 TI - Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson's Disease. AB - The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson's disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (~70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle. l-3,4 dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson's disease and related disorders. SIGNIFICANCE STATEMENT: Dopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson's disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson's disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response to l-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson's disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson's disease and potentially other basal-ganglia-related disorders. PMID- 26558772 TI - Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators. AB - The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT: Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID- 26558773 TI - Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions. AB - The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. SIGNIFICANCE STATEMENT: Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception. PMID- 26558774 TI - Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx. AB - Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT: Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled pharmacological treatments in both zebrafish and cultured mouse sensory neurons revealed that axonal calcium influx late in the degeneration process regulates axon fragmentation. These findings suggest that temporal considerations will be crucial for developing treatments for diseases associated with axon degeneration. PMID- 26558775 TI - Examining the Role of the Human Hippocampus in Approach-Avoidance Decision Making Using a Novel Conflict Paradigm and Multivariate Functional Magnetic Resonance Imaging. AB - Rodent models of anxiety have implicated the ventral hippocampus in approach avoidance conflict processing. Few studies have, however, examined whether the human hippocampus plays a similar role. We developed a novel decision-making paradigm to examine neural activity when participants made approach/avoidance decisions under conditions of high or absent approach-avoidance conflict. Critically, our task required participants to learn the associated reward/punishment values of previously neutral stimuli and controlled for mnemonic and spatial processing demands, both important issues given approach avoidance behavior in humans is less tied to predation and foraging compared to rodents. Participants played a points-based game where they first attempted to maximize their score by determining which of a series of previously neutral image pairs should be approached or avoided. During functional magnetic resonance imaging, participants were then presented with novel pairings of these images. These pairings consisted of images of congruent or opposing learned valences, the latter creating conditions of high approach-avoidance conflict. A data-driven partial least squares multivariate analysis revealed two reliable patterns of activity, each revealing differential activity in the anterior hippocampus, the homolog of the rodent ventral hippocampus. The first was associated with greater hippocampal involvement during trials with high as opposed to no approach avoidance conflict, regardless of approach or avoidance behavior. The second pattern encompassed greater hippocampal activity in a more anterior aspect during approach compared to avoid responses, for conflict and no-conflict conditions. Multivoxel pattern classification analyses yielded converging findings, underlining a role of the anterior hippocampus in approach-avoidance conflict decision making. SIGNIFICANCE STATEMENT: Approach-avoidance conflict has been linked to anxiety and occurs when a stimulus or situation is associated with reward and punishment. Although rodent work has implicated the hippocampus in approach-avoidance conflict processing, there is limited data on whether this role applies to learned, as opposed to innate, incentive values, and whether the human hippocampus plays a similar role. Using functional neuroimaging with a novel decision-making task that controlled for perceptual and mnemonic processing, we found that the human hippocampus was significantly active when approach-avoidance conflict was present for stimuli with learned incentive values. These findings demonstrate a role for the human hippocampus in approach avoidance decision making that cannot be explained easily by hippocampal dependent long-term memory or spatial cognition. PMID- 26558776 TI - Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion. AB - Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. SIGNIFICANCE STATEMENT: It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after selective hair cell lesion. Because these afferent neurons carry sound information from the cochlea to the auditory brainstem, their survival is a key determinant of the success of cochlear prosthetics. Our data suggest that fractalkine signaling in the cochlea is neuroprotective, and reveal a previously uncharacterized interaction between cells of the cochlea and the innate immune system. PMID- 26558777 TI - Epigenetic Readers of Lysine Acetylation Regulate Cocaine-Induced Plasticity. AB - Epigenetic processes that regulate histone acetylation play an essential role in behavioral and molecular responses to cocaine. To date, however, only a small fraction of the mechanisms involved in the addiction-associated acetylome have been investigated. Members of the bromodomain and extraterminal (BET) family of epigenetic "reader" proteins (BRD2, BRD3, BRD4, and BRDT) bind acetylated histones and serve as a scaffold for the recruitment of macromolecular complexes to modify chromatin accessibility and transcriptional activity. The role of BET proteins in cocaine-induced plasticity, however, remains elusive. Here, we used behavioral, pharmacological, and molecular techniques to examine the involvement of BET bromodomains in cocaine reward. Of the BET proteins, BRD4, but not BRD2 or BRD3, was significantly elevated in the nucleus accumbens (NAc) of mice and rats following repeated cocaine injections and self-administration. Systemic and intra accumbal inhibition of BRD4 with the BET inhibitor, JQ1, attenuated the rewarding effects of cocaine in a conditioned place preference procedure but did not affect conditioned place aversion, nor did JQ1 alone induce conditioned aversion or preference. Investigating the underlying mechanisms, we found that repeated cocaine injections enhanced the binding of BRD4, but not BRD3, to the promoter region of Bdnf in the NAc, whereas systemic injection of JQ1 attenuated cocaine induced expression of Bdnf in the NAc. JQ1 and siRNA-mediated knockdown of BRD4 in vitro also reduced expression of Bdnf. These findings indicate that disrupting the interaction between BET proteins and their acetylated lysine substrates may provide a new therapeutic avenue for the treatment of drug addiction. SIGNIFICANCE STATEMENT: Proteins involved in the "readout" of lysine acetylation marks, referred to as BET bromodomain proteins (including BRD2, BRD3, BRD4, and BRDT), have been shown to be key regulators of chromatin dynamics and disease, and BET inhibitors are currently being studied in several clinical trials. However, their role in addiction-related phenomena remains unknown. In the current studies, we revealed that BRD4 is elevated in the nucleus accumbens and recruited to promoter regions of addiction-related genes following repeated cocaine administration, and that inhibition of BRD4 attenuates transcriptional and behavioral responses to cocaine. Together, these studies reveal that BET inhibitors may have therapeutic utility in the treatment of cocaine addiction. PMID- 26558778 TI - Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice. AB - Previous studies have hypothesized that diverse genetic causes of intellectual disability (ID) and autism spectrum disorders (ASDs) converge on common cellular pathways. Testing this hypothesis requires detailed phenotypic analyses of animal models with genetic mutations that accurately reflect those seen in the human condition (i.e., have structural validity) and which produce phenotypes that mirror ID/ASDs (i.e., have face validity). We show that SynGAP haploinsufficiency, which causes ID with co-occurring ASD in humans, mimics and occludes the synaptic pathophysiology associated with deletion of the Fmr1 gene. Syngap(+/-) and Fmr1(-/y) mice show increases in basal protein synthesis and metabotropic glutamate receptor (mGluR)-dependent long-term depression that, unlike in their wild-type controls, is independent of new protein synthesis. Basal levels of phosphorylated ERK1/2 are also elevated in Syngap(+/-) hippocampal slices. Super-resolution microscopy reveals that Syngap(+/-) and Fmr1(-/y) mice show nanoscale alterations in dendritic spine morphology that predict an increase in biochemical compartmentalization. Finally, increased basal protein synthesis is rescued by negative regulators of the mGlu subtype 5 receptor and the Ras-ERK1/2 pathway, indicating that therapeutic interventions for fragile X syndrome may benefit patients with SYNGAP1 haploinsufficiency. SIGNIFICANCE STATEMENT: As the genetics of intellectual disability (ID) and autism spectrum disorders (ASDs) are unraveled, a key issue is whether genetically divergent forms of these disorders converge on common biochemical/cellular pathways and hence may be amenable to common therapeutic interventions. This study compares the pathophysiology associated with the loss of fragile X mental retardation protein (FMRP) and haploinsufficiency of synaptic GTPase-activating protein (SynGAP), two prevalent monogenic forms of ID. We show that Syngap(+/-) mice phenocopy Fmr1(-/y) mice in the alterations in mGluR dependent long-term depression, basal protein synthesis, and dendritic spine morphology. Deficits in basal protein synthesis can be rescued by pharmacological interventions that reduce the mGlu5 receptor-ERK1/2 signaling pathway, which also rescues the same deficit in Fmr1(-/y) mice. Our findings support the hypothesis that phenotypes associated with genetically diverse forms of ID/ASDs result from alterations in common cellular/biochemical pathways. PMID- 26558779 TI - Protein Phosphatase-1 Inhibitor-2 Is a Novel Memory Suppressor. AB - Reversible phosphorylation, a fundamental regulatory mechanism required for many biological processes including memory formation, is coordinated by the opposing actions of protein kinases and phosphatases. Type I protein phosphatase (PP1), in particular, has been shown to constrain learning and memory formation. However, how PP1 might be regulated in memory is still not clear. Our previous work has elucidated that PP1 inhibitor-2 (I-2) is an endogenous regulator of PP1 in hippocampal and cortical neurons (Hou et al., 2013). Contrary to expectation, our studies of contextual fear conditioning and novel object recognition in I-2 heterozygous mice suggest that I-2 is a memory suppressor. In addition, lentiviral knock-down of I-2 in the rat dorsal hippocampus facilitated memory for tasks dependent on the hippocampus. Our data indicate that I-2 suppresses memory formation, probably via negatively regulating the phosphorylation of cAMP/calcium response element-binding protein (CREB) at serine 133 and CREB-mediated gene expression in dorsal hippocampus. Surprisingly, the data from both biochemical and behavioral studies suggest that I-2, despite its assumed action as a PP1 inhibitor, is a positive regulator of PP1 function in memory formation. SIGNIFICANCE STATEMENT: We found that inhibitor-2 acts as a memory suppressor through its positive functional influence on type I protein phosphatase (PP1), likely resulting in negative regulation of cAMP/calcium response element-binding protein (CREB) and CREB-activated gene expression. Our studies thus provide an interesting example of a molecule with an in vivo function that is opposite to its in vitro function. PP1 plays critical roles in many essential physiological functions such as cell mitosis and glucose metabolism in addition to its known role in memory formation. PP1 pharmacological inhibitors would thus not be able to serve as good therapeutic reagents because of its many targets. However, identification of PP1 inhibitor-2 as a critical contributor to suppression of memory formation by PP1 may provide a novel therapeutic target for memory-related diseases. PMID- 26558780 TI - MEG Adaptation Resolves the Spatiotemporal Characteristics of Face-Sensitive Brain Responses. AB - An unresolved goal in face perception is to identify brain areas involved in face processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques identify the fusiform gyrus as subserving processing of invariant face features relating to identity. High temporal resolution imaging techniques localize an early latency evoked component the N/M170-as having a major generator in the fusiform region; however, this evoked component is not believed to be associated with the processing of identity. To resolve this, we used novel magnetoencephalographic beamformer analyses to localize cortical regions in humans spatially with trial-by-trial activity that differentiated faces and objects and to interrogate their functional sensitivity by analyzing the effects of stimulus repetition. This demonstrated a temporal sequence of processing that provides category-level and then item-level invariance. The right fusiform gyrus showed adaptation to faces (not objects) at ~150 ms after stimulus onset regardless of face identity; however, at the later latency of ~200-300 ms, this area showed greater adaptation to repeated identity faces than to novel identities. This is consistent with an involvement of the fusiform region in both early and midlatency face-processing operations, with only the latter showing sensitivity to invariant face features relating to identity. SIGNIFICANCE STATEMENT: Neuroimaging techniques with high spatial-resolution have identified brain structures that are reliably activated when viewing faces and techniques with high temporal resolution have identified the time-varying temporal signature of the brain's response to faces. However, until now, colocalizing face-specific mechanisms in both time and space has proven notoriously difficult. Here, we used novel magnetoencephalographic analysis techniques to spatially localize cortical regions with trial-by-trial temporal activity that differentiates between faces and objects and to interrogate their functional sensitivity by analyzing effects of stimulus repetition on the time-locked signal. These analyses confirm a role for the right fusiform region in early to midlatency responses consistent with face identity processing and convincingly deliver upon magnetoencephalography's promise to resolve brain signals in time and space simultaneously. PMID- 26558781 TI - Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact. AB - Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ~50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development. PMID- 26558783 TI - Cdk5 Regulates Activity-Dependent Gene Expression and Dendrite Development. AB - The proper growth and arborization of dendrites in response to sensory experience are essential for neural connectivity and information processing in the brain. Although neuronal activity is important for sculpting dendrite morphology, the underlying molecular mechanisms are not well understood. Here, we report that cyclin-dependent kinase 5 (Cdk5)-mediated transcriptional regulation is a key mechanism that controls activity-dependent dendrite development in cultured rat neurons. During membrane depolarization, Cdk5 accumulates in the nucleus to regulate the expression of a subset of genes, including that of the neurotrophin brain-derived neurotrophic factor, for subsequent dendritic growth. Furthermore, Cdk5 function is mediated through the phosphorylation of methyl-CpG-binding protein 2, a key transcriptional repressor that is mutated in the mental disorder Rett syndrome. These findings collectively suggest that the nuclear import of Cdk5 is crucial for activity-dependent dendrite development by regulating neuronal gene transcription during neural development. SIGNIFICANCE STATEMENT: Neural activity directs dendrite development through the regulation of gene transcription. However, how molecular signals link extracellular stimuli to the transcriptional program in the nucleus remains unclear. Here, we demonstrate that neuronal activity stimulates the translocation of the kinase Cdk5 from the cytoplasmic compartment into the nucleus; furthermore, the nuclear localization of Cdk5 is required for dendrite development in cultured neurons. Genome-wide transcriptome analysis shows that Cdk5 deficiency specifically disrupts activity dependent gene transcription of bdnf. The action of Cdk5 is mediated through the modulation of the transcriptional repressor methyl-CpG-binding protein 2. Therefore, this study elucidates the role of nuclear Cdk5 in the regulation of activity-dependent gene transcription and dendritic growth. PMID- 26558782 TI - Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke. AB - Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. SIGNIFICANCE STATEMENT: There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long-term functional recovery is an important outcome in patients. In an attempt to identify agents that promote functional recovery, we discovered that an FDA-approved soy isoflavone, daidzein, improved stroke-induced behavioral deficits via enhancing cholesterol homeostasis in chronic stroke, and this occurs without causing adverse effects in the acute phase. With its known safety in humans, the study suggests that the early and chronic use of daidzein serves as a potential strategy to promote functional recovery in stroke patients. PMID- 26558784 TI - Separating Visual and Motor Components of Motor Cortex Activation for Multiple Reach Targets: A Visuomotor Adaptation Study. AB - Ethologically inspired models of movement preparation view the sensorimotor system as sampling information from the environment in a parallel fashion in preparation for multiple potential actions. In support, the configuration of the physical workspace, manipulated by the number or spatial separation of potential targets, has been shown to modulate sensorimotor neural activity. It is unclear, however, whether this modulation is driven by the sensory layout of the workspace or through the associated motor plans. Here, we combine a delayed-movement pre cuing task with visuomotor adaptation to address this question in human subjects while recording MEG. By dissociating visual and motor coordinates of two targets using visuomotor adaptation, the task was designed to evaluate, in a selective fashion, the effects of visual and movement target separation on movement preparatory activity. The results did not allow the intended comparison due to an unanticipated effect of the direction of visuomotor adaptation on baseline oscillatory power in beta and low-gamma bands. Fortuitously, this effect was dependent on whether the adaptation direction decreased or increased the angular separation between alternative movements. That is, there was a sustained reduction of oscillatory power, which was stronger at small compared with large target separation. These results support a direct influence of movement target separation on motor cortex neural activity, mediated by lateral interactions between simultaneously active motor plans. The results further demonstrate a novel effect of visuomotor adaptation on motor cortex oscillatory activity, with properties that support the local nature of learned changes in visuomotor mapping. SIGNIFICANCE STATEMENT: There is growing evidence that the motor cortex routinely prepares for different movements simultaneously, each suited to a possible course of events in the immediate environment. The preparatory motor cortex activity for different movements can be seen as a competition between groups of neurons. This competition is influenced by how similar the alternative movements are; for example, in terms of direction, determined by the proximity of alternative movement goals. This study investigates whether the proximity of alternative reach goals has a direct influence on motor cortex activity (in the form of brain oscillations) or if it has an effect only through conscious evaluation of the separation between targets. We establish that there is a direct effect, supporting the biased competition model of action selection. PMID- 26558785 TI - Human Amygdala Represents the Complete Spectrum of Subjective Valence. AB - Although the amygdala is a major locus for hedonic processing, how it encodes valence information is poorly understood. Given the hedonic potency of odor stimuli and the amygdala's anatomical proximity to the peripheral olfactory system, we combined high-resolution fMRI with pattern-based multivariate techniques to examine how valence information is encoded in the amygdala. Ten human subjects underwent fMRI scanning while smelling 9 odorants that systematically varied in perceived valence. Representational similarity analyses showed that amygdala codes the entire dimension of valence, ranging from pleasantness to unpleasantness. This unidimensional representation significantly correlated with self-reported valence ratings but not with intensity ratings. Furthermore, within-trial valence representations evolved over time, prioritizing earlier differentiation of unpleasant stimuli. Together, these findings underscore the idea that both spatial and temporal features uniquely encode pleasant and unpleasant odor valence in the amygdala. The availability of a unidimensional valence code in the amygdala, distributed in both space and time, would create greater flexibility in determining the pleasantness or unpleasantness of stimuli, providing a mechanism by which expectation, context, attention, and learning could influence affective boundaries for guiding behavior. SIGNIFICANCE STATEMENT: Our findings elucidate the mechanisms of affective processing in the amygdala by demonstrating that this brain region represents the entire valence dimension from pleasant to unpleasant. An important implication of this unidimensional valence code is that pleasant and unpleasant valence cannot coexist in the amygdale because overlap of fMRI ensemble patterns for these two valence extremes obscures their unique content. This functional architecture, whereby subjective valence maps onto a pattern continuum between pleasant and unpleasant poles, offers a robust mechanism by which context, expectation, and experience could alter the set-point for valence-based behavior. Finally, identification of spatial and temporal differentiation of valence in amygdala may shed new insights into individual differences in emotional responding, with potential relevance for affective disorders. PMID- 26558786 TI - The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to beta Amyloid Oligomer-Related Neurotoxicity and Memory Impairment. AB - In Alzheimer's disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2alpha, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for beta-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for beta-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer's disease. SIGNIFICANCE STATEMENT: Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress sensing calcium-permeable channel that is thought to contribute to calcium dysregulation associated with neurodegenerative diseases, including Alzheimer's disease. Here we show that oligomeric beta-amyloid, the toxic peptide in Alzheimer's disease, facilitates TRPM2 channel activation. In mice designed to model Alzheimer's disease, genetic elimination of TRPM2 normalized deficits in synaptic markers in aged mice. Moreover, the absence of TRPM2 improved age-dependent spatial memory deficits observed in Alzheimer's mice. Our results reveal the importance of TRPM2 for neuronal toxicity and memory impairments in an Alzheimer's mouse model and suggest that TRPM2 could be targeted for the development of therapeutic agents effective in the treatment of dementia. PMID- 26558787 TI - Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis. AB - Mitochondrial changes, including decreased expression of electron transport chain subunit genes and impaired energetic, have been reported in multiple sclerosis (MS), but the mechanisms involved in these changes are not clear. To determine whether epigenetic mechanisms are involved, we measured the concentrations of methionine metabolites by liquid chromatography tandem mass spectrometry, histone H3 methylation patterns, and markers of mitochondrial respiration in gray matter from postmortem MS and control cortical samples. We found decreases in respiratory markers as well as decreased concentrations of the methionine metabolites S-adenosylmethionine, betaine, and cystathionine in MS gray matter. We also found expression of the enzyme betaine homocysteine methyltransferase in cortical neurons. This enzyme catalyzes the remethylation of homocysteine to methionine, with betaine as the methyl donor, and has previously been thought to be restricted to liver and kidney in the adult human. Decreases in the concentration of the methyl donor betaine were correlated with decreases in histone H3 trimethylation (H3K4me3) in NeuN+ neuronal nuclei in MS cortex compared with controls. Mechanistic studies demonstrated that H3K4me3 levels and mitochondrial respiration were reduced in SH-SY5Y cells after exposure to the nitric oxide donor sodium nitroprusside, and betaine was able to rescue H3K4me3 levels and respiratory capacity in these cells. Chromatin immunoprecipitation experiments showed that betaine regulates metabolic genes in human SH-SY5Y neuroblastoma cells. These data suggest that changes to methionine metabolism may be mechanistically linked to changes in neuronal energetics in MS cortex. SIGNIFICANCE STATEMENT: For decades, it has been observed that vitamin B12 deficiency and multiple sclerosis (MS) share certain pathological changes, including conduction disturbances. In the present study, we have found that vitamin B12-dependent methionine metabolism is dysregulated in the MS brain. We found that concentrations of the methyl donor betaine are decreased in MS cortex and are correlated with reduced levels of the histone H3 methyl mark H3K4me3 in neurons. Cell culture and chromatin immunoprecipitation-seq data suggest that these changes may lead to defects in mitochondria and impact neuronal energetics. These data have uncovered a novel pathway linking methionine metabolism with mitochondrial respiration and have important implications for understanding mechanisms involved in neurodegeneration in MS. PMID- 26558788 TI - Beta-Band Oscillations Represent Auditory Beat and Its Metrical Hierarchy in Perception and Imagery. AB - Dancing to music involves synchronized movements, which can be at the basic beat level or higher hierarchical metrical levels, as in a march (groups of two basic beats, one-two-one-two ...) or waltz (groups of three basic beats, one-two-three one-two-three ...). Our previous human magnetoencephalography studies revealed that the subjective sense of meter influences auditory evoked responses phase locked to the stimulus. Moreover, the timing of metronome clicks was represented in periodic modulation of induced (non-phase locked) beta-band (13-30 Hz) oscillation in bilateral auditory and sensorimotor cortices. Here, we further examine whether acoustically accented and subjectively imagined metric processing in march and waltz contexts during listening to isochronous beats were reflected in neuromagnetic beta-band activity recorded from young adult musicians. First, we replicated previous findings of beat-related beta-power decrease at 200 ms after the beat followed by a predictive increase toward the onset of the next beat. Second, we showed that the beta decrease was significantly influenced by the metrical structure, as reflected by differences across beat type for both perception and imagery conditions. Specifically, the beta-power decrease associated with imagined downbeats (the count "one") was larger than that for both the upbeat (preceding the count "one") in the march, and for the middle beat in the waltz. Moreover, beamformer source analysis for the whole brain volume revealed that the metric contrasts involved auditory and sensorimotor cortices; frontal, parietal, and inferior temporal lobes; and cerebellum. We suggest that the observed beta-band activities reflect a translation of timing information to auditory-motor coordination. SIGNIFICANCE STATEMENT: With magnetoencephalography, we examined beta-band oscillatory activities around 20 Hz while participants listened to metronome beats and imagined musical meters such as a march and waltz. We demonstrated that beta-band event-related desynchronization in the auditory cortex differentiates between beat positions, specifically between downbeats and the following beat. This is the first demonstration of beta-band oscillations related to hierarchical and internalized timing information. Moreover, the meter representation in the beta oscillations was widespread across the brain, including sensorimotor and premotor cortices, parietal lobe, and cerebellum. The results extend current understanding of the role of beta oscillations in neural processing of predictive timing. PMID- 26558790 TI - Modulation of Tonically Active Neurons of the Monkey Striatum by Events Carrying Different Force and Reward Information. AB - The role of basal ganglia in motivational processes has been under scrutiny in recent decades, with increasing evidence from clinical studies of cognitive and motivational deficits in patients with basal ganglia lesions. Tonically active neurons (TANs), the presumed striatal cholinergic interneurons, could be important actors in integrating and relaying motivational information arising from various modalities. Their multiphasic responses to rewards and to conditioned stimuli associated with reward conferred them a role in limbic processes. They are also modulated by a task's motor aspect. Recent studies suggest they are influenced by the context in which behavioral responses are expressed. To investigate the role of TANs in motor-limbic interaction processes, we recorded 169 TANs in the striatum of two monkeys performing a motivational task, in which they had to develop a variable force to receive different amounts of reward in response to visual stimuli. Our results reveal new features of TANs response properties. First, TANs usually responded either by a pause or an elevation of discharge rate to the visual cues and the reward, with few neurons combining both pause and rebound. Second, the elevations of discharge rate after the cues were most sensitive to the least valuable (high force or small reward) task conditions. Finally, the responses of TANs to the visual cues were time locked on the onset of the animal's movement. TANs' population and responses could thus play a role in signaling less attractive situations, those with either a high motor demand and/or small reward. SIGNIFICANCE STATEMENT: Tonically active neurons (TANs) are known for their responses to unpredictable positive or negative events. However, here we show that TANs respond by a pause or an increase in their activity to all rewarding events in a task in which combined visual cues indicate to the monkeys the levels of force to produce and the upcoming reward. Unlike the pause, the increase in activity is modulated by task parameters and is most sensitive to the least attractive task conditions (high force and/or small reward). TANs' responses triggered by cue occurrence are also modulated by movement-related information (movement onset). We therefore propose here that TANs could play a role, via their action on striatal projections neurons, in maintaining high cost/low benefit ratio behaviors. PMID- 26558789 TI - Reciprocal Regulation of Mitochondrial Dynamics and Calcium Signaling in Astrocyte Processes. AB - We recently showed that inhibition of neuronal activity, glutamate uptake, or reversed-Na(+)/Ca(2+)-exchange with TTX, TFB-TBOA, or YM-244769, respectively, increases mitochondrial mobility in astrocytic processes. In the present study, we examined the interrelationships between mitochondrial mobility and Ca(2+) signaling in astrocyte processes in organotypic cultures of rat hippocampus. All of the treatments that increase mitochondrial mobility decreased basal Ca(2+). As recently reported, we observed spontaneous Ca(2+) spikes with half-lives of ~1 s that spread ~6 MUm and are almost abolished by a TRPA1 channel antagonist. Virtually all of these Ca(2+) spikes overlap mitochondria (98%), and 62% of mitochondria are overlapped by these spikes. Although tetrodotoxin, TFB-TBOA, or YM-244769 increased Ca(2+) signaling, the specific effects on peak, decay time, and/or frequency were different. To more specifically manipulate mitochondrial mobility, we explored the effects of Miro motor adaptor proteins. We show that Miro1 and Miro2 are both expressed in astrocytes and that exogenous expression of Ca(2+)-insensitive Miro mutants (KK) nearly doubles the percentage of mobile mitochondria. Expression of Miro1(KK) had a modest effect on the frequency of these Ca(2+) spikes but nearly doubled the decay half-life. The mitochondrial proton ionophore, FCCP, caused a large, prolonged increase in cytosolic Ca(2+) followed by an increase in the decay time and the spread of the spontaneous Ca(2+) spikes. Photo-ablation of mitochondria in individual astrocyte processes has similar effects on Ca(2+). Together, these studies show that Ca(2+) regulates mitochondrial mobility, and mitochondria in turn regulate Ca(2+) signals in astrocyte processes. SIGNIFICANCE STATEMENT: In neurons, the movement and positioning of mitochondria at sites of elevated activity are important for matching local energy and Ca(2+) buffering capacity. Previously, we demonstrated that mitochondria are immobilized in astrocytes in response to neuronal activity and glutamate uptake. Here, we demonstrate a mechanism by which mitochondria are immobilized in astrocytes subsequent to increases in intracellular [Ca(2+)] and provide evidence that mitochondria contribute to the compartmentalization of spontaneous Ca(2+) signals in astrocyte processes. Immobilization of mitochondria at sites of glutamate uptake in astrocyte processes provides a mechanism to coordinate increases in activity with increases in mitochondrial metabolism. PMID- 26558791 TI - Automated 3D closed surface segmentation: application to vertebral body segmentation in CT images. AB - PURPOSE: A fully automated segmentation algorithm, progressive surface resolution (PSR), is presented in this paper to determine the closed surface of approximately convex blob-like structures that are common in biomedical imaging. The PSR algorithm was applied to the cortical surface segmentation of 460 vertebral bodies on 46 low-dose chest CT images, which can be potentially used for automated bone mineral density measurement and compression fracture detection. METHODS: The target surface is realized by a closed triangular mesh, which thereby guarantees the enclosure. The surface vertices of the triangular mesh representation are constrained along radial trajectories that are uniformly distributed in 3D angle space. The segmentation is accomplished by determining for each radial trajectory the location of its intersection with the target surface. The surface is first initialized based on an input high confidence boundary image and then resolved progressively based on a dynamic attraction map in an order of decreasing degree of evidence regarding the target surface location. RESULTS: For the visual evaluation, the algorithm achieved acceptable segmentation for 99.35 % vertebral bodies. Quantitative evaluation was performed on 46 vertebral bodies and achieved overall mean Dice coefficient of 0.939 (with max [Formula: see text] 0.957, min [Formula: see text] 0.906 and standard deviation [Formula: see text] 0.011) using manual annotations as the ground truth. CONCLUSIONS: Both visual and quantitative evaluations demonstrate encouraging performance of the PSR algorithm. This novel surface resolution strategy provides uniform angular resolution for the segmented surface with computation complexity and runtime that are linearly constrained by the total number of vertices of the triangular mesh representation. PMID- 26558792 TI - Pica and Eating Attitudes: A Study of High-Risk Pregnancies. AB - OBJECTIVE: To describe and determine the association between the occurrence of pica and eating attitudes in women with high-risk pregnancies and to determine the prevalence of pica during pregnancy. METHODS: A cross-sectional and prospective 24-month study was conducted with 913 women with high-risk pregnancies. Structured interviews were carried out and the Eating Attitudes Test was applied. RESULTS: Pica was diagnosed in 5.7 % of the pregnant women, and its most commonly practiced type was geophagia (57.7 %). The association between pica and signs related to the eating attitudes: "to be considered too thin by others" (p < 0.02), and "to spend too much time thinking about food" (p = 0.05); and the association between pica and the risk of both anorexia nervosa and bulimia nervosa (p < 0.01) were statistically significant. CONCLUSIONS: The absence of validated instruments in the literature for assessing pica reinforces the difficulty of investigating this practice and the need for further studies. Moreover, additional efforts need to focus in the improvement of screening for other eating disorders with obstetric consequences associated with pica and be incorporated into the routine of healthcare professionals. PMID- 26558793 TI - Microbial deglycosylation and ketonization of ginsenoside by Cladosporium cladosporioide and their anticancer activity. AB - Ginseng has been used for thousands of years in Asian countries as a traditional medicinal herb and has gained great popularity in the past decade. Ginsenosides are the major pharmacological components in ginseng. We here show that Cladosporium cladosporioide is able to convert the major ginsenoside Rb1 into four known metabolites (ginsenosides Rd, F2, CK and PPD) and two new metabolites [12beta-hydroxydammar-3-one-20(S)-O-beta-D-glucopyranoside (3-oxo-CK) and dammar 24-en-12beta,20(S)-diol-3-one (3-oxo-PPD)]. CK, PPD and 3-oxo-PPD were shown to have a potent antiproliferative activity against A549 lung cancer cells. We found that Rb1 -> Rd -> F2 -> CK -> PPD or 3-oxo-CK -> 3-oxo-PPD represents the ginsenoside metabolic pathway. PMID- 26558794 TI - Diversity and antimicrobial potential of bacterial isolates associated with the soft coral Alcyonium digitatum from the Baltic Sea. AB - It is well recognized that microorganisms associated with marine invertebrates, in particular sponges and hard corals, are an excellent source of new natural products. Therefore, the diversity of bacteria associated with marine invertebrates and their potential to produce bioactive compounds have received much attention in recent years. We report here for the first time on the biodiversity of bacteria associated with the soft coral Alcyonium digitatum, which is abundant in the Baltic Sea. In order to increase the cultured diversity, bacteria were isolated using four different media, identified with support of 16S rRNA gene sequences and screened for antimicrobial activity using two different media. Activity of crude extracts was tested against Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, and the yeast Candida albicans. A total of 251 coral-associated bacterial isolates were classified and found to belong to 41 species in 14 genera of the Firmicutes, Actinobacteria, Gammaproteobacteria, and Alphaproteobacteria. The genus Bacillus was most abundant and diverse with 17 recognized species. Forty-eight percent of all 251 isolates exhibited antimicrobial activity. All isolates of Bacillus methylotrophicus and Bacillus amyloliquefaciens displayed inhibition of at least three out of the four tested microorganisms. It became obvious during this study that the production of antibiotic substances not only is strain-specific, but in many cases also depends on the media composition and growth conditions. In addition, the antimicrobial potential of bacteria associated with A. digitatum may represent a promising source for antimicrobial substances. PMID- 26558795 TI - Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. AB - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL). METHODS: A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant. RESULTS: Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC NCL were older (67.5 +/- 12.3 vs. 62.7 +/- 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p < 0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p > 0.05). CONCLUSION: Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost effectiveness of HCC surveillance in this group should be conducted. PMID- 26558797 TI - Telehealth Utilization for Chronic Illness and Depression Among Home Health Agencies: A Pilot Survey. AB - This pilot survey study explores current telehealth use among home health care agencies for chronic illness and depression care, and identifies factors associated with agencies' perception and intention to use telehealth. Between June and August 2014, 73 directors and 13 staff nurses (N = 86) from the Pennsylvania Homecare Association member agencies participated in an online survey. Eighty-five percent of telehealth provider agencies reported utilizing telehealth for monitoring health status while only 7.7% reported use for depression care. Telehealth technology was more positively perceived for chronic illness care (90.7%) than for depression care (53%) services. Factors associated with positive perceptions of telehealth were identified, including: (a) intention to use or continuing to use telehealth, (b) the size of the agency, (c) the participant's agency role, and (d) existence of depression services. These pilot findings have been used to inform the theoretical framework and the survey instrument for our U.S. national survey. PMID- 26558798 TI - NHS money is wasted on short term action rather than fixing the underlying problems. PMID- 26558799 TI - Efficacy of fulvestrant 500 mg in Japanese postmenopausal advanced/recurrent breast cancer patients and factors associated with prolonged time-to-treatment failure. AB - OBJECTIVE: We aimed to confirm the efficacy of fulvestrant in Japanese postmenopausal advanced/recurrent breast cancer (ABC) patients, and investigate factors contributing to time-to-treatment failure (TTF) prolongation. RESEARCH DESIGN AND METHODS: This retrospective study included 194 ABC patients who received fulvestrant (500 mg) from January 2012 to December 2014. MAIN OUTCOME MEASURES: TTF (efficacy measure), overall survival (OS), factors prolonging TTF and adverse events were evaluated. RESULTS: The median age was 65 (42 - 90) years. Overall, TTF was 5.48 months. In patients without prior chemotherapy (n = 59), OS was significantly longer (p = 0.0131) than in patients with prior chemotherapy (n = 135). There was no strong correlation between TTF with fulvestrant and other endocrine therapies, total duration of endocrine therapy and maximum duration of endocrine therapy. TTF was significantly longer in patients with less than two prior chemotherapy regimens (p = 0.0093), de novo metastatic disease (p = 0.0124) and without liver metastasis (p = 0.0024). We observed one case each of pulmonary infarction and psychiatric disorder. CONCLUSIONS: Fulvestrant is effective for ABC patients and may show greater efficacy in patients with few prior chemotherapy regimens, de novo metastatic disease and absence of liver metastasis. Prior endocrine therapy duration might not be a predictive factor for fulvestrant TTF in heavily treated ABC patients. PMID- 26558800 TI - Two new C19-diterpenoid alkaloids from Aconitum straminiflorum. AB - Two new C19-diterpenoid alkaloids, straconitines A (1) and B (2), were isolated from the roots of Aconitum straminiflorum. Their structures were elucidated as 14 benzoylducloudine D (1) and 6-hydroxy-14-benzoylducloudine D (2) based on spectroscopic analysis, including IR, ESI-MS, HR-ESI-MS, 1D, and 2D NMR. PMID- 26558801 TI - Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. AB - BACKGROUND: Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during controlled ovarian hyperstimulation (COH) prior to planned oocyte retrieval, thus optimising the chances of live birth. OBJECTIVES: To evaluate the effectiveness of the different GnRHa protocols as adjuncts to COH in women undergoing ART cycles. SEARCH METHODS: We searched the following databases from inception to April 2015: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, CINAHL, PsycINFO, and registries of ongoing trials. Reference lists of relevant articles were also searched. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any two protocols of GnRHa used in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles in subfertile women. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed trial eligibility and risk of bias, and extracted the data. The primary outcome measure was number of live births or ongoing pregnancies per woman/couple randomised. Secondary outcome measures were number of clinical pregnancies, number of oocytes retrieved, dose of gonadotrophins used, adverse effects (pregnancy losses, ovarian hyperstimulation, cycle cancellation, and premature luteinising hormone (LH) surges), and cost and acceptability of the regimens. We combined data to calculate odds ratios (OR) for dichotomous variables and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main comparisons using 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methods. MAIN RESULTS: We included 37 RCTs (3872 women), one ongoing trial, and one trial awaiting classification. These trials made nine different comparisons between protocols. Twenty of the RCTs compared long protocols and short protocols. Only 19/37 RCTs reported live birth or ongoing pregnancy.There was no conclusive evidence of a difference between a long protocol and a short protocol in live birth and ongoing pregnancy rates (OR 1.30, 95% CI 0.94 to 1.81; 12 RCTs, n = 976 women, I2 = 15%, low quality evidence). Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. There was evidence of an increase in clinical pregnancy rates (OR 1.50, 95% CI 1.18 to 1.92; 20 RCTs, n = 1643 women, I2 = 27%, moderate quality evidence) associated with the use of a long protocol.There was no evidence of a difference between the groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort protocol (OR 1.78, 95% CI 0.72 to 4.36; one RCT, n = 150 women, low quality evidence), long luteal versus long follicular phase protocol (OR 1.89, 95% CI 0.87 to 4.10; one RCT, n = 223 women, low quality evidence), when GnRHa was stopped versus when it was continued (OR 0.75, 95% CI 0.42 to 1.33; three RCTs, n = 290 women, I2 = 0%, low quality evidence), when the dose of GnRHa was reduced versus when the same dose was continued (OR 1.02, 95% CI 0.68 to 1.52; four RCTs, n = 407 women, I2 = 0%, low quality evidence), when GnRHa was discontinued versus continued after human chorionic gonadotrophin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; one RCT, n = 181 women, low quality evidence), and when administration of GnRHa lasted for two versus three weeks before stimulation (OR 1.14, 95% CI 0.49 to 2.68; one RCT, n = 85 women, low quality evidence). Our primary outcomes were not reported for any other comparisons.Regarding adverse events, there were insufficient data to enable us to reach any conclusions except about the cycle cancellation rate. There was no conclusive evidence of a difference in cycle cancellation rate (OR 0.95, 95% CI 0.59 to 1.55; 11 RCTs, n = 1026 women, I2 = 42%, low quality evidence) when a long protocol was compared with a short protocol. This suggests that in a population in which 9% of women would have their cycles cancelled using a short protocol, between 5.5% and 14% will have cancelled cycles when using a long protocol.The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years. AUTHORS' CONCLUSIONS: When long GnRHa protocols and short GnRHa protocols were compared, we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates, but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects. PMID- 26558802 TI - Salmonella typhimurium in the Australian egg industry: Multidisciplinary approach to addressing the public health challenge and future directions. AB - In Australia, numerous egg-related human Salmonella typhimurium outbreaks have prompted significant interest among public health authorities and the egg industry to jointly address this human health concern. Nationwide workshops on Salmonella and eggs were conducted in Australia for egg producers and regulatory authorities. State and national regulators represented Primary Production, Communicable Disease Control, Public Health and Food Safety, and Food Standards Australia and New Zealand. All attendees participated in discussions aimed at evaluating current evidence-based information, issues related to quality of egg production, and how to ensure safe eggs in the supply chain, identifying research gaps and practical recommendations. The perceptions from egg producers and regulatory authorities from various states were recorded during the workshops. We presented the issues discussed during the workshops, including Salmonella in the farm environment, Salmonella penetration across eggshell, virulence in humans, food/egg handling in the supply chain, and intervention strategies. We also discussed the perceptions from egg producers and regulators. Recommendations placed emphasis on the future research needs, communication between industry and regulatory authorities, and education of food handlers. Communication between regulators and industry is pivotal to control egg-borne S. typhimurium outbreaks, and collaborative efforts are required to design effective and appropriate control strategies. PMID- 26558803 TI - The role of theory-based outcome frameworks in program evaluation: Considering the case of contribution analysis. AB - In an era demanding greater accountability and the demonstration of positive outcomes and impacts, the field for the evaluation of interventions, program development and outreach projects is being challenged in many fields, including education, medical care, public health and social development. In consequence, the leaders in this field significantly changed their approaches to the evaluation of such interventions. Evaluators noted that simple linear models of evaluation do not address the wider community of interests and stakeholders involved in today's innovative and wide-reaching programs. Moreau raises the possible usefulness of contribution analysis in responding to the calls for broader accountability. In this commentary, the elements of these emerging approaches are reviewed and explained for teachers with reporting responsibilities in health sciences education. The presentation is intended to expand on Moreau's argument and suggestions such that educators may be able to consider the use of theory-based evaluations, such as contribution analyses, in the evaluation of their institutional programs and interventions. These possible applications are especially relevant to the increasingly more complicated and complex interventions that characterize many of the educational interventions as more health profession programs are moved into and impact on the larger societal community. PMID- 26558804 TI - Connecting medical education to patient outcomes: The promise of contribution analysis. AB - This article presents a promising program evaluation approach, contribution analysis, which can be used to demonstrate the link between medical education programs and patient outcomes. Contribution analysis is a theory-based evaluation approach. It views programs as a part of causal packages that work together with other factors, interventions, and influences to bring about changes in specific outcomes. Although this approach is well suited for evaluating medical education programs, it has not yet been used in this area. PMID- 26558807 TI - Genomic Characterization of Poorly Differentiated Neuroendocrine Carcinoma in a Pediatric Patient. AB - Primary neuroendocrine carcinomas (NEC) are rare tumors in children and young adults, resulting in a lack of standardized treatment approach. To refine the molecular taxonomy of these rare tumors, we performed whole exome sequencing in a pediatric patient with mediastinal NEC. We identified a somatic mutation in HRAS gene and LOH regions in NF2, MYO18B, and RUX3 genes. In addition, a germline heterozygous somatic variant in BRCA2 with LOH at that same position in the tumor tissue was also found. Our data provide valuable insight into the genomic landscape of this tumor, prompting further investigation of therapeutic targets. PMID- 26558808 TI - Visual Field Loss in a Case of Recurrent Cystic Craniopharyngioma During Concomitant Treatment With Pegylated Interferon alpha-2b. AB - A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon alpha-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon alpha-2b was discontinued. Given the recent interest in interferon alpha-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery. PMID- 26558806 TI - Potential therapeutic approaches for Angelman syndrome. AB - INTRODUCTION: Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of maternally inherited UBE3A, an ubiquitin E3 ligase. Despite recent progress in understanding the mechanism underlying UBE3A imprinting, there is no effective treatment. Further investigation of the roles played by UBE3A in the central nervous system (CNS) is needed for developing effective therapies. AREA COVERED: This review covers the literature related to genetic classifications of AS, recent discoveries regarding the regulation of UBE3A imprinting, alterations in cell signaling in various brain regions and potential therapeutic approaches. Since a large proportion of AS patients exhibit comorbid autism spectrum disorder (ASD), potential common molecular bases are discussed. EXPERT OPINION: Advances in understanding UBE3A imprinting provide a unique opportunity to induce paternal UBE3A expression, thus targeting the syndrome at its 'root.' However, such efforts have yielded less-than-expected rescue effects in AS mouse models, raising the concern that activation of paternal UBE3A after a critical period cannot correct all the CNS defects that developed in a UBE3A-deficient environment. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects in preclinical research. Thus, combined reinstatement of paternal UBE3A expression with targeting abnormal signaling pathways should provide better therapeutic effects. PMID- 26558809 TI - The Incidence of Hypersensitivity Reactions to Pegylated Asparaginase in Children With Acute Lymphoblastic Leukemia: A City-wide Experience. AB - Asparaginase (ASNase) is an imperative component of pediatric acute lymphoblastic leukemia (ALL) therapy. Pegylating the ASNase extends its biological half-life in vivo and has become the only ASNase available in the United States for frontline therapy of ALL and lymphoblastic lymphoma. It is either infused intravenously (IV) or injected intramuscularly (IM), administrations of which are associated with hypersensitivity reaction ranging from localized skin reaction to severe anaphylaxis. A retrospective review of 96 medical records of pediatric ALL patients was performed. We compared the incidence of hypersensitivity reaction associated with IV versus IM administration of pegylated ASNase. Ninety-one patients were included in the final analysis; 31 having received pegylated ASNase IV and 60 receiving it IM. The incidence of any grade >= 2 hypersensitivity reaction in patients who received IV ASNase was 32.2% compared with 13.3% in the IM group (P=0.032). There was no difference in higher grade hypersensitivity reactions (19.4% vs. 11.7%). Most reactions tended to occur during periods of leukemia therapy that did not include concomitant steroid therapy. Our retrospective analysis indicates that IV administration of pegylated ASNase increases the incidence of low-grade, but not grade 3-4, hypersensitivity reactions compared with IM administration. PMID- 26558810 TI - Vancomycin Therapeutic Targets and Nephrotoxicity in Critically Ill Children With Cancer. AB - To obtain pharmacokinetic and pharmacodynamic data for vancomycin in a cohort of critically ill pediatric oncology patients, we analyzed 256 measurements of vancomycin concentrations in 94 patients. Variables were tested as possible risk factors for vancomycin-related nephrotoxicity or death for 28 days. We found the following: mean vancomycin trough serum concentration, 15.6 +/- 12.4 MUg/mL; mean vancomycin clearance, 0.16 +/- 0.098 L/h/kg; and mean vancomycin distribution volume, 1.04 +/- 0.11 L/kg. Only 13.6% of serum trough level measurements were between 15 and 20 MUg/mL. The trough levels showed a strong correlation with the AUC (area under the curve of serum concentrations vs. time over 24 h to the minimum inhibitory concentration ratio), with a 94% positive predictive value for AUC/MIC >= 400, but only for MIC=1. The doses that are currently used (60 mg/kg/d) attained the therapeutic target (AUC/MIC >= 400) in only 56% of measurements, considering MIC=1. A serum trough level of >= 20 MUg/mL was an independent risk for nephrotoxicity (P = 0.0008; odds ratio = 17.83). Vancomycin related nephrotoxicity was a predictor of death for up to 28 days (P = 0.003, odds ratio = 7.68). Currently administered doses of vancomycin do not reach the therapeutic target for critical cancer patients, particularly if staphylococci isolates have a MIC>1. PMID- 26558811 TI - The Clinical Significance of Voriconazole Therapeutic Drug Monitoring in Children With Invasive Fungal Infections. AB - Voriconazole is an antifungal drug used to treat fungal infections. This was a retrospective study of 61 children with hemato-oncologic diseases or solid organ transplantation who were administered voriconazole for invasive fungal infections. Of the 61 patients, 31 (50.8%) were in the therapeutic drug monitoring (TDM) group, and 30 (49.2%) were in the non-TDM group. At 12 weeks, treatment failure rate in the non-TDM group was higher than the TDM group (78.6% versus 40.0%, p = 0.038). Drug discontinuation due to adverse events was less frequent in the TDM group than the non-TDM group (26.0% versus 92.3%, p = 0.001). Children required higher dosages to maintain drug levels within the targeted therapeutic range: an average of 8.3 mg/kg/dose in patients <12 years old and 6.9 mg/kg/dose for those >=12 years old. Treatment failure rates were higher in patients whose voriconazole levels remained below 1.0 mg/L for more than 50% of their treatment duration than those above 1.0 mg/L (71.4% vs. 9.1% after 12 weeks, p = 0.013). Serial monitoring of voriconazole levels in children is important for improving treatment response and preventing unnecessary drug discontinuation. Higher dosages are needed in children to reach therapeutic range. PMID- 26558812 TI - The relationship between premature birth and caregiver first concern in toddlers with autism spectrum disorder: A brief report. AB - The current study examines the relationship between premature birth and the age at which caregivers first become concerned with their child's development in a sample of 84 toddlers with autism spectrum disorder (ASD). The participants were split into two groups: those born prematurely and those born full term. The results indicate that the age of caregiver first concern is significantly younger for those born prematurely than those born full term. The average age caregivers reported first becoming concerned about their child's development was around 7 months for participants born prematurely and around 13 months for participants born full term. Possible explanations for the results and their implications are discussed. PMID- 26558813 TI - Potential benefits of pentoxifylline on wound healing. AB - In this review, potential benefits of pentoxifylline (PTX) on wound healing have been evaluated. All available experimental and clinical studies examined effects of PTX on wound healing have been included. No time limitation was considered and all studies up to writing the manuscript were included. Administration of oral or parenteral PTX showed beneficial effects on the healing of colorectal anastomosis, post burn scar, radiation-induced skin/soft tissue injury, venous ulcers, recurrent aphthous stomatitis and cutaneous/mucocutaneous leishmaniasis. Data regarding effect of PTX on skin flap survival are conflicting. Only few evidences support promising effects of PTX in pressure ulcer, skin developing injury and burn. PMID- 26558814 TI - Molecular histology of arteries: mass spectrometry imaging as a novel ex vivo tool to investigate atherosclerosis. AB - Atherosclerosis is usually the underlying cause of a fatal event such as myocardial infarction or ictus. The atherome plaque develops silently and asymptomatically within the arterial intima layer. In this context, the possibility to analyze the molecular content of arterial tissue while preserving each molecule's specific localization is of great interest as it may reveal further insights into the physiopathological changes taking place. Mass spectrometry imaging (MSI) enables the spatially resolved molecular analysis of proteins, peptides, metabolites, lipids and drugs directly in tissue, with a resolution sufficient to reveal molecular features specific to distinct arterial structures. MSI represents a novel ex vivo imaging tool still underexplored in cardiovascular diseases. This review focuses on the MSI technique applied to cardiovascular disease and covers the main contributions to date, ongoing efforts, the main challenges and current limitations of MSI. PMID- 26558815 TI - Toward the dynamic phase transition mechanism of a thermoresponsive ionic liquid in the presence of different thermoresponsive polymers. AB - The influence of two thermoresponsive polymers, poly(N-isopropylacrylamide) (PNIPAM) and poly(N-vinylcaprolactam) (PVCL), on the phase transition behavior of a thermoresponsive ionic liquid, tributylhexylphosphonium 3 sulfopropylmethacrylate ([P4,4,4,6][MC3S]), was investigated. An obvious distinction was observed in the LCSTs and morphologies of [P4,4,4,6][MC3S]-PNIPAM and [P4,4,4,6][MC3S]-PVCL aqueous solutions, indicating their large differences in dynamic transition processes. In general, PNIPAM can "break" the water structure of [P4,4,4,6][MC3S] to decrease the transition temperature, while PVCL can "make" the water structure to increase it. Surprisingly, [P4,4,4,6][MC3S] has an unusual over-hydration behavior before dehydration while PNIPAM experiences a two-step transition process in [P4,4,4,6][MC3S]-PNIPAM aqueous solution, which has never been reported so far. Further studies revealed that the formation of strong intra-/inter-molecular hydrogen bonds C[double bond, length as m-dash]OD-N in PNIPAM is the driving force for the LCST phenomenon of [P4,4,4,6][MC3S]-PNIPAM solution, while it is the [P4,4,4,6][MC3S] that dominates the phase separation of [P4,4,4,6][MC3S]-PVCL solution. PMID- 26558816 TI - The coping strategies of front-line health workers in the context of user fee exemptions in Niger. AB - When user fee exemptions were introduced for children under five years of age in Niger, front-line staff in the health system were not consulted in advance, and various obstacles seriously hindered the policy's implementation. Health workers developed two types of coping strategies. The first dealt with shortcomings of the policy implementation process related to management tools, drug stocks, co existence of the fee exemption and cost recovery systems, and, above all, supply management for medicines (ordering from private companies, issuing makeshift prescriptions). The second involved clientelism, circumvention of regulations, and misappropriation of resources. Adverse effects have arisen due to both the failings of the health system and the practices of health workers. These include a focus on the commercial management of patients, the most 'costly' of whom sometimes find themselves being refused treatment, patients roaming in search of medicines and treatment, and a decline in quality of care. PMID- 26558819 TI - Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure: Insights From SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. AB - High nighttime and early morning blood pressure (BP) have been associated with greater risk for cardiovascular events than high clinic or daytime BP. BP is typically highest in the rising hours, when morning activities typically begin. We examined the effect of renal denervation on morning (6:00-8:59 AM), daytime (9:00 AM-8:59 PM), and nighttime (1:00-5:59 AM) ambulatory BP. Patient data from 2 prospective, randomized controlled trials of patients with treatment-resistant, uncontrolled hypertension, one conducted in a US population (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]) and the other in a Japanese population (SYMPLICITY HTN-Japan [HTN-Japan]), were analyzed. Patients in SYMPLICITY HTN-3 and HTN-Japan were prescribed a similar number of baseline antihypertensive medications (5.2+/-1.4 versus 4.9+/-1.6, P=0.28), but the classes prescribed and changes in prescription varied by study. Among patients treated with renal denervation, although the number of ablation treatments were similar in both studies (11.2+/-2.8 versus 11.5+/-1.9, P=0.55), patients in SYMPLICITY HTN-3 were less likely to receive at least 1 four-quadrant ablation treatment (25% versus 82%, P<0.001). In SYMPLICITY HTN-3, compared with controls (n=159), patients treated with renal denervation (n=325) experienced a significantly greater change in morning (-7.3+/-19.8 mm Hg, P<0.001) and nighttime (-6.1+/-18.2 versus -1.6+/-19.7 mm Hg, P=0.02) but not daytime systolic BP (-7.2+/-16.2 versus -6.4+/-18.6 mm Hg, P=0.67). This same trend was observed in the pooled analysis with HTN-Japan. Reduction of BP during these high-risk periods might provide cardiovascular protection in drug-resistant hypertensive patients, although this will need to be proved in future randomized trials. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov; Unique identifiers: NCT01418261 (SYMPLICITY HTN-3) and NCT01644604 (HTN-Japan). PMID- 26558821 TI - Correction. AB - In the article by Narayan et al (Narayan O, Davies JE, Hughes AD, Dart AM, Parker KH, Reid C, Cameron JD. Central aortic reservoir-wave analysis improves prediction of cardiovascular events in elderly hypertensives. Hypertension. 2015;65:629-635. doi: 10.1161/HYPERTENSIONAHA.114.04824), which published online ahead of print December 22, 2014, and appeared in the March 2015 issue of the journal, some corrections were needed.On page 632, Figure, panel A, the label PRI has been corrected to read RPI. In panel B, the text by the upward arrow, "10% increase in kd," has been corrected to read, "10% decrease in kd." The corrected figure is shown below.The authors apologize for these errors. PMID- 26558818 TI - Childhood to Early-Midlife Systolic Blood Pressure Trajectories: Early-Life Predictors, Effect Modifiers, and Adult Cardiovascular Outcomes. AB - Previous studies examining blood pressure change over time have modeled an average population trajectory. Recent research among older adults suggests there may be subgroups with different blood pressure trajectories. Identifying subgroups at risk of developing adult hypertension early in life can inform effective risk reduction efforts. We sought to identify different systolic blood pressure trajectories from childhood, their correlated risk factors, and early midlife cardiovascular outcomes. Blood pressure data at ages 7, 11, 18, 26, 32, and 38 years from a longitudinal, representative birth cohort study (n=975) were used to identify 4 distinct trajectory groups via group-based trajectory modeling: normal (21.8%), high-normal (43.3%), prehypertensive (31.6%), and hypertensive (4.2%). The categories refer to blood pressure beginning at the age of 7 years and most recently measured at the age of 38 years. Family history of high blood pressure (odds ratio [OR], 43.23; 95% confidence interval [CI], 5.27 354.65), male sex (OR, 109.48; 95% CI, 26.82-446.96), being first born (OR, 2.5; 95% CI, 1.00-8.69) and low birth weight (OR, 2.79; 95% CI, 2.49-3.09) were associated with hypertensive group membership (compared with the normal group). Higher body mass index and cigarette smoking resulted in increasing blood pressure across trajectories, particularly for the higher blood pressure groups. Prehypertensive and hypertensive trajectory groups had worse cardiovascular outcomes by early midlife. Harmful blood pressure trajectories are identifiable in childhood, associated with both antecedent and modifiable risk factors over time, and predict adult cardiovascular disease risk. Early detection and subsequent targeted prevention and intervention may reduce the lifecourse burden associated with higher blood pressure. PMID- 26558822 TI - Management of waste electrical and electronic equipment in Romania: A mini review. AB - Around the world there are growing concerns for waste electrical and electronic equipment. This is motivated by the harmful effects of waste electrical and electronic equipment on the environment, but also by the perspectives of materials recovery. Differences between countries regarding waste electrical and electronic equipment management are notable in the European Union. Romania is among the countries that have made significant efforts to comply with European Union regulations, but failed reaching the collection target. The article presents a mini review of the waste electrical and electronic equipment management system in Romania, based on legislation and policy documents, statistical data, research studies and reports published by national and international organisations. The article debates subjects like legislative framework, the electrical and electronic equipment Romanian market, the waste electrical and electronic equipment collection system, waste electrical and electronic equipment processing and waste electrical and electronic equipment behaviour. The recast of the European directive brings new challenges to national authorities and to other stakeholders involved in the waste electrical and electronic equipment management. Considering the fact that Romania has managed a collection rate of roughly 1 kg capita(-1) in the last years, the new higher collection targets established by the waste electrical and electronic equipment Directive offer a serious challenge for the management system. Therefore, another aim of the article is to highlight the positive and negative aspects in the Romanian waste electrical and electronic equipment field, in order to identify the flows that should be corrected and the opportunities that could help improve this system to the point of meeting the European standards imposed by the European Directive. PMID- 26558820 TI - Leukotriene B4 Activates Pulmonary Artery Adventitial Fibroblasts in Pulmonary Hypertension. AB - A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension. LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of this study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast proliferation, migration, and differentiation in a dose-dependent manner through its cognate G-protein-coupled receptor, BLT1. LTB4 activated human pulmonary artery adventitial fibroblast by upregulating p38 mitogen-activated protein kinase as well as Nox4-signaling pathways. In an autoimmune model of pulmonary hypertension, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation, and attenuated pulmonary hypertension development. This study uncovers a novel mechanism by which LTB4 further promotes pulmonary arterial hypertension pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID- 26558823 TI - Human Intestinal Raf Kinase Inhibitor Protein (RKIP) Catalyzes Prasugrel as a Bioactivation Hydrolase. AB - Prasugrel is a thienopyridine antiplatelet prodrug that undergoes rapid hydrolysis in vivo to a thiolactone metabolite by human carboxylesterase-2 (hCE2) during gastrointestinal absorption. The thiolactone metabolite is further converted to a pharmacologically active metabolite by cytochrome P450 isoforms. The aim of the current study was to elucidate hydrolases other than hCE2 involved in the bioactivation step of prasugrel in human intestine. Using size-exclusion column chromatography of a human small intestinal S9 fraction, another peak besides the hCE2 peak was observed to have prasugrel hydrolyzing activity, and this protein was found to have a molecular weight of about 20 kDa. This prasugrel hydrolyzing protein was successfully purified from a monkey small intestinal cytosolic fraction by successive four-step column chromatography and identified as Raf-1 kinase inhibitor protein (RKIP) by liquid chromatography-tandem mass spectrometry. Second, we evaluated the enzymatic kinetic parameters for prasugrel hydrolysis using recombinant human RKIP and hCE2 and estimated the contributions of these two hydrolyzing enzymes to the prasugrel hydrolysis reaction in human intestine, which were approximately 40% for hRKIP and 60% for hCE2. Moreover, prasugrel hydrolysis was inhibited by anti-hRKIP antibody and carboxylesterase specific chemical inhibitor (bis p-nitrophenyl phosphate) by 30% and 60%, respectively. In conclusion, another protein capable of hydrolyzing prasugrel to its thiolactone metabolite was identified as RKIP, and this protein may play a significant role with hCE2 in prasugrel bioactivation in human intestine. RKIP is known to have diverse functions in many intracellular signaling cascades, but this is the first report describing RKIP as a hydrolase involved in drug metabolism. PMID- 26558824 TI - The natural history of cardiovascular risk factors in health professionals: 20 year follow-up. AB - BACKGROUND: The knowledge of the presence and evolution of cardiovascular risk factors in young people may significantly contribute to actions to modify the natural history of these risks and prevent the onset of cardiovascular disease. OBJECTIVES: To assess the presence and evolution of cardiovascular risk factors in health professionals over a 20-year period. METHODS: A group of individuals was evaluated when they first started graduate programs in medicine, nursing, nutrition, dentistry, and pharmacy, and 20 years later. Data obtained in the two phases were compared. Questionnaires about hypertension, diabetes, hypercholesterolemia, family history of early-onset cardiovascular disease, smoking, alcohol consumption, and sedentary lifestyle were administered. Cholesterol, blood glucose, blood pressure, weight, height, and body mass index (BMI) were measured. RESULTS: Of the 281 individuals (62.9 % women; mean age 19.7 years) initially analyzed, 215 (59.07 % women; mean age 39.8 years) were analyzed 20 years later. An increase in mean values of systolic (111.6 vs 118.7 mmHg- p < 0.001) and diastolic blood pressure (71 vs 77.1 mmHg - p < 0.001), cholesterol (150.1 vs 182.4 mg/dL - p < 0.001), blood glucose (74.3 vs 81.4 mg/dL - p < 0.001) and BMI (20.7 vs 23.7 kg/m(2) - p = 0.017) was observed. Despite the decrease of sedentarism (50.2 vs 38.1 % - p = 0.015), the prevalence of hypertension (4.6 vs 18.6 % - p < 0.001), excessive weight (8.2 vs 32.1 % - p < 0.001), hypercholesterolemia (7.8 vs 24.2 % - p < 0.001), and alcohol consumption (32.7 vs 34.9 % - p = 0.037) increased. There was no change in the prevalence of smoking. CONCLUSION: Health professionals presented an increase in systolic and diastolic blood pressure, blood glucose, body mass index, and cholesterol over the 20-year study period. Regarding the prevalence of cardiovascular risk factors, increased blood pressure, overweight, hypercholesterolemia and alcohol consumption, and a decrease in sedentary lifestyle were observed. PMID- 26558826 TI - Half-life of a printed handoff document. AB - BACKGROUND: Printed handoff documents are nearly universally present in the pockets of providers taking inhouse call. They are frequently used to answer clinical questions. However, the static nature of printed documents makes it likely that information will quickly become inaccurate as a result of ongoing management. This increases the potential for medical errors, especially in clinical services which rely heavily on printed documents for ongoing patient management. OBJECTIVE: To measure the average time to potential inaccuracy, represented as the 'half-life' of printed handoff documents. DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of 100 adult inpatients during a single 24 h period at an academic medical centre in 2014. MAIN OUTCOME AND MEASURE: The half-life was defined as the time at which half of the patients would be expected to have inaccurate information on a printed handoff document, based on review of orders which populate data fields on these printed handoff documents. RESULTS: In our sample, the half-life was 6 h on the 12 h night shift and 3.3 h on the day shift. We identified at least on change within the 24 h period for 92% of patients. Most changes (90% n=1411) were medication-related, but the overall distribution of order types was significantly different between day and night (p=0.002). CONCLUSIONS AND RELEVANCE: The accuracy of printed handoff documents quickly deteriorated over the course of a physician shift. Based on this decay rate, a typical physician getting sign-out on 20 patients overnight can safely assume that the data for 10 of them will be inaccurate or outdated in 6 h and that it will be inaccurate on another two by the morning. PMID- 26558825 TI - Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study. AB - BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity related quantitative traits in two Danish cohorts. METHODS: Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) >=25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index >=25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z scores) stratifying on the case status and adjusting for age and gender. Meta analyses were performed using the fixed effects model. RESULTS: No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (beta = -0.12, p = 0.0026). CONCLUSIONS: The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark. PMID- 26558827 TI - Author response: from analysis to learning. PMID- 26558828 TI - Opportunities for incident reporting. Response to: 'The problem with incident reporting' by Macrae et al. PMID- 26558829 TI - "I never expected that it would happen, coming to ask me such questions":Ethical aspects of asking children about violence in resource poor settings. AB - BACKGROUND: International epidemiological research into violence against children is increasing in scope and frequency, but little has been written about practical management of the ethical aspects of conducting such research in low and middle income countries. In this paper, we describe our study procedures and reflect on our experiences conducting a survey of more than 3,700 primary school children in Uganda as part of the Good Schools Study, a cluster randomised controlled trial of a school-based violence prevention intervention. Children were questioned extensively about their experiences of physical, sexual, and emotional violence from a range of different perpetrators. We describe our sensitisation and consent procedures, developed based on our previous research experience and requirements for our study setting. To respond to disclosures of abuse that occurred during our survey, we describe a referral algorithm developed in conjunction with local services. We then describe our experience of actually implementing these procedures in our 2012 survey, based on reflections of the research team. Drawing on 40 qualitative interviews, we describe children's experiences of participating in the survey and of being referred to local child protection services. RESULTS: Although we were able to implement much of our protocol in a straightforward manner, we also encountered major challenges in relation to the response of local services to children's disclosures of violence. The research team had to intervene to ensure that children were provided with appropriate support and that our ethical obligations were met. CONCLUSIONS: In resource poor settings, finding local services that can provide appropriate support for children may be challenging, and researchers need to have concrete plans and back-up plans in place to ensure that obligations can be met. The merits of mandatory reporting of children's disclosures to local services need to be considered on a case by case basis-in some places this has the potential to do harm. Research teams also must agree on what level of ancillary care will be provided, and budget accordingly. Further practical examples of how to address the challenges encountered in this work are needed, in order to build a consensus on best practices. TRIAL REGISTRATION: NCT01678846 (clinicaltrials.gov), August 24, 2012. PMID- 26558830 TI - INR variability and outcomes in patients with mechanical heart valve prosthesis. AB - BACKGROUND: The quality of treatment with warfarin is mainly assessed by the time in therapeutic range (TTR) in patients with mechanical heart valve prosthesis (MHV). Our aim was to evaluate if International Normalized Ratio (INR) variability predicted a combined endpoint of thromboembolism, major bleeding and death better than TTR. METHODS AND RESULTS: We included 394 patients at one center with MHV during 2008-2011 with adverse events and death followed prospectively. TTR 2.0-4.0 and log-transformed INR variability was calculated for all patients. In order to make comparisons between the measures, the gradient of the risk per one standard deviation (SD) was assessed. INR variability performed equal as TTR 2.0-4.0 per one SD unit adjusted for covariates, hazard ratio (HR) 1.30 (95% CI 1.1-1.5) and 0.71 (95% CI 0.6-0.8) respectively for the combined endpoint, and performed better for mortality HR 1.47 (95% CI 1.1-1.9) and 0.70 (95% CI 0.6-0.8). INR variability was categorized into high and low group and TTR into tertiles. High variability within the low and high TTR, had a HR 2.0 (95% CI 1.7-3.6) and 2.2 (95% CI 1.1-4.1) respectively, of the combined endpoint compared to the low variability/high TTR group. INR values <2.0 greatly increased the rate of thromboembolism whereas the rate of major bleeding increased moderately between INR 3.0 and 4.0 and increased substantially after INR >4.0. CONCLUSION: The INR variability is an equal predictor as TTR of the combined endpoint of thromboembolism, major bleeding and death, and adds important information on top of TTR in patients with MHV. PMID- 26558831 TI - Changes in muscle damage, inflammation, and fatigue-related parameters in young elite soccer players after a match. AB - BACKGROUND: Professional soccer players are subjected to substantial physical loads during competitive seasons. We aimed to explore the changes induced by a soccer match on muscle damage and inflammation biomarkers, and their relationship with fatigue parameters. METHODS: Twenty young male professional in-field soccer players from an Italian Serie A team (age 17-20 years, weight 73.0+/-7.0 kg, height 1.81+/-0.05m) played a 90-minute soccer match. Players' distances and velocities were recorded during the match. Before the match and 30 minutes, 24 and 48 hours after the match, blood samples were drawn and a full blood cell count was determined, along with serum creatine kinase (CK), interleukin 6 (hsIL 6), cortisol and testosterone. At the same time intervals, counter-movement jump (CMJ) performance was recorded. RESULTS: The players covered fewer meters at low velocities in the second period while the meters covered at higher intensity remained unchanged. CMJ height was lower at all postgame time-points compared to the pregame measurement. Immediately after the match, CK, hs-IL6 and neutrophil counts were elevated. 24 and 48 hours after the match, CK and neutrophil counts remained significantly elevated. The distance covered during the game was found to be correlated with the values for postmatch hsIL-6 (rho=0.521, P=0.027), post 24-hour cortisol (r=0.502, P=0.034) and the increase in cortisol at 48 hours with respect to prematch values (r=0.515, P=0.029). CONCLUSIONS: A soccer match provokes a transient systemic imbalance that results in muscle damage and inflammatory and performance-related parameter changes. HsIL-6 and cortisol could be used to monitor recovery processes and as fatigue markers, even for short time periods. PMID- 26558832 TI - Acute physiological changes in elite free-style wrestlers during a one-day tournament. AB - BACKGROUND: The purpose of this study was to examine free radical production, muscle damage and inflammation responses of well-trained wrestlers to a simulated one-day tournament of free-style wrestling. METHODS: Twelve elite competitive wrestlers with mean age (+/-SD) of 24.09+/-6.20 years, body mass 74.09+/-11.50 kg, and body height 174.90+/-8.8 cm and who had competed for national teams completed five matches according to the official Olympic wrestling tournament regulations. Blood sampling was collected before and after fifth match. Baseline blood testing was measured at 10:00 a.m. and then matches started at 12:00. Each match was implemented within one hour. Also, the resting time was 45 minutes following each match. The measurements were analyzed by Wilcoxon Signed Ranks Test, which is used to test for significant differences between pre- and post test. RESULTS: The post-match lactate dehydrogenase (LDH), creatine kinase (CK), and interleukin (IL)-6 levels were significantly increased compared with the baseline status. However, baseline malondialdehyde levels were not found significantly different compared with post-match. CONCLUSIONS: The current study ensured that one-day Free-Style wrestling tournament brings about significantly increasing on CK, LDH of muscle damage markers. Also, inflammatory status showed a progressive worsening during the course of one-day tournament. The study showed enhanced muscle damage markers and inflammatory status after one-day Free-Style wrestling tournament. Therefore, it appears that one-day free-style wrestling tournament imposes significant physiological demands on wrestlers that may adversely affect their performance and inflammatory status, thereby putting the athletes in a greater risk for injury. PMID- 26558833 TI - Effects on power, strength and lean body mass of menstrual/oral contraceptive cycle based resistance training. AB - BACKGROUND: The purpose of this study was to investigate the effects of menstrual and oral contraceptive cycle on a high frequency periodized leg resistance training in trained women. METHODS: Two groups performed high frequency leg resistance training for two weeks of each menstrual/oral contraceptive cycle for four months. The remaining part of the cycle they performed the leg training once a week. Group 1 (N.=19) trained with high frequency (5 times?w-1) during the first two weeks of each cycle, and group 2 (N.=19) during the last two weeks of each cycle. A control group (N.=21) performed regurlar (3 times?w-1) leg resistance training for four months. RESULTS: Significant increase in squat and countermovement jump, and peak torque values in hamstrings for group 1 were observed, but not in group 2. In the control group an increase in squat and countermovement jump, and peak torque (only left hamstring) was also observed. There was also a significant increase in lean body mass of the legs in group 1 only. There were no evident differences in the training effects between women with or without oral contraceptive. CONCLUSIONS: The high frequency periodized leg resistance training during the first two weeks of the menstrual cycle is more beneficial to optimize training than in the last two weeks. Resistance training during the first two weeks of the menstrual cycle even resulted in a larger gain of lean body mass than regular training. PMID- 26558834 TI - Ground surface nature can influence visual information contribution in postural control. AB - BACKGROUND: In sport, the nature of ground surface is likely to influence the contribution of visual information on postural control. Boxing and wrestling are respectively practiced on firm and soft ground surfaces. The aim was to compare the postural control of boxers with that of wrestlers on stable (firm) and unstable (soft and dynamic) ground surfaces, with and without deprivation of vision. METHODS: Fifteen male international boxers and 15 male international wrestlers presenting the same anthropometrics characteristics and the same number of years of sports practice were recruited. Spatiotemporal parameters of displacement of the center of feet pressure (COP) were measured on a force platform in static (firm and foam surfaces with eyes open and eyes closed) and dynamic conditions (medio/lateral and antero-posterior directions with eyes open and eyes closed). RESULTS: The results mainly showed a significant vision * group interaction in the antero-posterior direction for the dynamic postural condition (P<0.017). This indicated that the contribution of visual information was greater for the boxers than for the wrestlers in challenging condition (P=0.030). CONCLUSIONS: Further studies are needed to confirm whether the nature of ground surface influences the contribution of visual information, which can be, in turn, affected by the specificity of motor skills. PMID- 26558835 TI - Acute inflammatory response to prolonged sculling in competitive male rowers. AB - BACKGROUND: This study examined the effects of a prolonged low-intensity single scull rowing exercise on a complex of 12 different inflammatory cytokines in rowers. METHODS: Twenty male rowers (19.0+/-2.9 yrs; 185.6+/-4.8 cm; 85.7+/-10.8 kg; 17.1+/-5.1% body fat; maximal oxygen consumption [VO2max]: 63.9+/-8.5 mL.min. 1kg-1) completed a rowing training session lasting about 2-h (distance: 21.4+/ 1.8 km; heart rate [HR]: 139+/-8 beats.min-1; intensity: 79.9+/-3.6% of the anaerobic threshold) followed by a 30-min rest. Venous blood samples were collected before and after on-water rowing, and analyzed for blood white cell count (WBC), high sensitive C-reactive protein (hsCRP), and 12 inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma, tumor necrosis factor-alpha, IL-1alpha, IL 1beta, monocyte chemotactic protein-1 [MCP-1], epidermal growth factor). RESULTS: Exercise induced significant (P<0.05) increment in WBC, hsCRP, IL-6, IL-10 and MCP-1 concentrations. The long-distance sculling intensity variables such as the average rating of perceived exertion, HR and blood lactate were correlated with changes in IL-8, IL-1alpha and IL-1beta levels (r=0.47 to r=0.59; P<0.05). Maximal aerobic performance variables (VO2max and maximal aerobic power) were related to changes in IL-2, IL-4, IL-8 and IL-1beta levels (r=-0.45 to r=-0.54; P<0.05). CONCLUSIONS: Acute exercise-induced inflammatory reaction was reflected by a significant increase in serum IL-6, IL-10 and MCP-1 levels. Variance in exercise-induced increases in inflammatory markers in response to 2-h of endurance exercise was explained by aerobic performance and exercise intensity levels in competitive male rowers. PMID- 26558836 TI - Effect of isometric handgrip training on resting blood pressure in adults: a meta analysis of randomized controlled trials. AB - INTRODUCTION: The aims of this study were to update the meta-analysis of the effect of isometric handgrip (IHG) training on resting systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in healthy adults, and to analyze the association between IHG training and participants with different initial BP status. EVIDENCE ACQUISITION: PubMed, EMBASE, and Cochrane library were searched for eligible studies until Nov. 24, 2014. Cochran's Q statistic and the I2 statistic were used to assess the heterogeneity among included studies, and for the homogeneous outcomes (P>=0.05 and I2<50%) a fixed-effects model was selected for meta-analysis, while a random-effects model was applied for heterogeneous outcomes (P<0.05 or I2>=50%). Mean difference (MD) with 95% confidence interval (CI) was calculated to evaluate the effects of IHR on participants. EVIDENCE SYNTHESIS: A total of 7 trials from 6 articles were included, consisting of 157 subjects. The results suggested that SBP (MD=-8.33, 95% CI: -11.19 to -5.46; P<0.01) and DBP (MD=-3.93, 95% CI: -6.14 to -1.72; P<0.01) were significantly decreased in IHG training group compared with control group. In subgroup analysis, SBP, DBP, and HR were all significantly decreased in prehypertensive subjects (P<0.01). In medicated hypertensive subgroup and normotensive subgroup, only SBP and DBP were significantly reduced (P<0.01). CONCLUSIONS: IHG training lowers resting SBP and DBP in healthy adults, and IHG training may be an efficacious form of clinical treatment or prevention of hypertension. PMID- 26558837 TI - Decreased interlimb differences in female basketball players. AB - BACKGROUND: Hand preference can be influenced by some factors like sensory information and sports participation. In many sports, it is always desirable to have the similar performance of both hands to adapt to the fast changes of the game. Elite basketball players use their left non-dominant hand more accurately and more frequently during the game compared to amateurs. However, there is no quantitative data to explain this phenomenon. The aim of the study was to test whether participation of long-term basketball training influences interlimb difference and also observed more accurate and more frequent usage of the non dominant hand in basketball players that can be explained by some kinematic variables during an aiming task. METHODS: Professional right-handed female basketball players and age-matched non-athletes were asked to reach one of three targets in a virtual reality environment setup with either their non-dominant or dominant hand. Two kinematic parameters depicting motor performance asymmetries were measured: accuracy and hand path deviation from linearity (HPDL). RESULTS: No interlimb differences for basketball players but significant asymmetrical performance for non-athletes were observed. Although the aiming task used in this study is not a basketball specific task, basketball players still displayed better performance compared to non-athletes in both accuracy and HPDL. CONCLUSIONS: The current study implies that not only sensorimotor information but also participation of long-term sports activity can modify interlimb difference. Moreover, basketball players having symmetrical motor performance of both hands, which was found in this study, can indirectly explain the more frequent usage of the non-dominant left hand in basketball players. PMID- 26558838 TI - Sleep recovery in participants after racing in the Finnmarkslop - Europe's longest dog-sled race. AB - BACKGROUND: During the dog-sled race, the Finnmarkslop (FL), which lasts up to 7 days, participants get little sleep and what they get is fragmented; concerns have been raised about proper sleep recovery. The aim of this study was to examine awareness of sleep deprivation by FL participants and post-race sleep recovery after completion of the race. METHODS: A total of 55 participants responded to an online survey 1 week and 1 month after the race; this measured the following factors: their awareness of sleep loss and possible strategies for recovery; their sleep-wake patterns using a Pittsburgh Sleep Questionnaire Index; and possible changes in respondents' sleep-wake patterns compared with their regular routines. RESULTS: During the FL, participants slept about 3-4 hours a day. Many were not aware of the accumulated sleep debt and did not engage in strategies to make up the loss. Insufficient levels of sleep and impoverished sleep quality were observed after the race, especially among those who were engaged in the FL for a longer period. Alertness levels were affected 1 week after the race. CONCLUSIONS: Among participants in the FL, the lack of awareness of sleep debt and insufficient sleep recovery could lead to health consequences. Those engaged in the race for longer should be more cautious during the recovery process because of possible sleep problems occurring after the race. Educational campaigns and easy access to professional support should be provided for participants in this type of sporting event. PMID- 26558840 TI - Paenibacillus cavernae sp. nov., isolated from soil of a natural cave. AB - A Gram-reaction-variable, strictly aerobic, motile, rod-shaped bacterium, designated strain C4-5T, was isolated from soil of a natural cave. Cells were oxidase- and catalase-positive and formed endospores in sporangia. The 16S rRNA gene sequence comparison showed that the organism formed a distinct clade within the genus Paenibacillus and was most closely related to Paenibacillus contaminans CKOBP-6T ( = KCTC 13623T) (96.85 % 16S rRNA gene sequence similarity) followed by Paenibacillus doosanensis CAU 1005T ( = KCTC 33036T) (94.82 %). The following chemotaxonomic features of strain C4-5T are typical for the genus Paenibacillus: meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan, MK-7 as the predominant menaquinone, the major fatty acids of anteiso-C15 : 0, iso-C16 : 0 and C16 : 0 and the DNA G+C content of 54.8 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and four unidentified aminophospholipids. The phenotypic and phylogenetic data presented support that strain C4-5T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus cavernae sp. nov. is proposed. The type strain is C4-5T ( = KCTC 33652T = DSM 100100T). PMID- 26558839 TI - Validation of an Age-adjusted Prostate Cancer-Specific Comorbidity Index. AB - Estimating competing mortality is of paramount importance for prostate cancer screening candidates and men with early prostate cancer. An age-adjusted prostate cancer-specific comorbidity index (PCCI) was developed recently for this purpose in an unselected population of 1598 men. We validated this mortality index in a sample of 2961 patients who consecutively underwent radical prostatectomy between 1992 and 2007 at our institution. In patients with a PCCI of 0, 1-2, 3-4, 5-6, 7 9, and >=10 who were selected for radical prostatectomy, the 10-yr competing mortality rates were 2%, 9%, 17%, 27%, 56%, and 0% (n=3), respectively, compared with 10%, 19%, 35%, 60%, 79%, and 99%, respectively, in the unselected development cohort. The PCCI is well suited to stratify patients with prostate cancer according to their risk of competing mortality. In candidates for radical prostatectomy, however, the 10-yr competing mortality rates are approximately half as high as in unselected patients with the same PCCI risk level. PATIENT SUMMARY: With stratification by the age-adjusted prostate cancer-specific comorbidity index, the 10-yr competing mortality rate in men selected for radical prostatectomy is approximately half as high as in unselected patients at the same level of comorbid risk. PMID- 26558841 TI - Effect of co-morbidities on the development of oral feeding ability in pre-term infants: a retrospective study. AB - Pre-term infants frequently experience difficulties in attaining independent oral feeding, thus delaying the achievement of an adequate nutritional status and hospital discharge. The aim of this retrospective, single-centre, observational study was to investigate the effect of co-morbidities on the timing of the achievement of full oral feeding in pre-term infants. The neonatal and feeding data of 84 infants born at a gestational age of <32 weeks were collected, and the effect of co-morbidities on the achievement of feeding independence was evaluated using multiple linear regression analysis. The mean postmenstrual age at the time of the achievement of full oral feeding was 36.7 +/- 3.68 weeks (range 33-53) weeks. The multiple linear regression analysis showed that a low birth weight, the occurrence of bronchopulmonary dysplasia, and the need for gastrointestinal surgical procedures were independently associated with a higher postmenstrual age at achievement of full oral feedings. PMID- 26558842 TI - Cofilin 1 activation prevents the defects in axon elongation and guidance induced by extracellular alpha-synuclein. AB - Impaired adult neurogenesis and axon traumatic injury participate in the severity of neurodegenerative diseases. Alpha-synuclein, a cytosolic protein involved in Parkinson's disease, may be released from neurons, suggesting a role for excess secreted alpha-synuclein in the onset and spread of the pathology. Here we provide evidence that long term exposure of young neurons to extracellular alpha synuclein hampers axon elongation and growth cone turning. We show that actin turnover and the rate of movement of actin waves along the axon are altered, due to alpha-synuclein-induced inactivation of cofilin. Upon laser disruption of microfilaments, healing of axons is favored by the increased phosphorylation of cofilin, however, at later time points; the defect in neurite extension prevails, being lost the regulation of cofilin activity. Importantly, overexpression of the active form of cofilin in neurons exposed to alpha-synuclein is able to restore the movement of actin waves, physiological axon elongation and growth cone turning. Our study reveals the molecular basis of alpha-synuclein-driven deficits in growth and migration of newborn neurons, and in elongation and regeneration of adult neurons. PMID- 26558843 TI - Electromyographic Comparison of Elastic Resistance and Machine Exercises for High Intensity Strength Training in Patients With Chronic Stroke. AB - OBJECTIVE: To investigate whether elastic resistance training can induce comparable levels of muscle activity as conventional machine training in patients with chronic stroke. DESIGN: Comparative study. SETTING: Outpatient rehabilitation facility. PARTICIPANTS: Stroke patients (N=18) with hemiparesis (mean age, 57 +/- 8y). INTERVENTIONS: Patients performed 3 consecutive repetitions at 10 repetition maximum of unilateral knee extension and flexion using elastic resistance and conventional machine training. MAIN OUTCOME MEASURES: Surface electromyography was measured in vastus lateralis, vastus medialis, biceps femoris, and semitendinosus and was normalized to maximal electromyography (% of max) of the nonparetic leg. RESULTS: In the paretic leg, agonist muscle activity ranged from 18% to 24% normalized electromyography (% of max) (nEMG) during knee flexion and from 32% to 40% nEMG during knee extension. For knee extension, vastus lateralis nEMG was higher during machine exercise than during elastic resistance exercise (40% [95% confidence interval {CI}, 33-47] vs 32% [95% CI, 25-39]; P=.003). In the nonparetic leg, agonist muscle activity ranged from 54% to 61% during knee flexion and from 52% to 68% during knee extension. For knee flexion semitendinosus nEMG was higher (61% [95% CI, 50-71] vs 54% [95% CI, 44-64]; P=.016) and for knee extension vastus medialis nEMG was higher (68% [95% CI, 60-76] vs 56% [95% CI, 48-64]; P<.001) during machine exercise than during elastic resistance exercise. By contrast, antagonist coactivation was significantly higher during knee flexion when performed using elastic resistance compared with the machine. Lastly, there were no differences in perceived exertion between exercise modalities. CONCLUSIONS: Machine training appears to induce slightly higher levels of muscle activity in some of the investigated muscles compared to elastic resistance during lower limb strength training in patients with chronic stroke. The higher level of coactivation during knee flexion when performed using elastic resistance suggests that elastic resistance exercises are more difficult to perform. This is likely due to a higher level of movement instability. PMID- 26558844 TI - Whither Research Domain Criteria (RDoC)?: The Good, the Bad, and the Ugly. PMID- 26558845 TI - Preparing for imported Ebola cases in Israel, 2014 to 2015. AB - During the current outbreak of Ebola virus disease (EVD) in West Africa, preventing exportation of the disease posed many challenges for economically more developed countries. In Israel, although the risk of importing single cases was assumed to be low, the implications of local transmission were great. This article describes the EVD preparedness plan of the Israeli Ministry of Health. Key elements were a sensitive case definition, designation of a single treatment centre for suspected and confirmed cases, construction of a mobile unit using customised negative-pressure tents and a vigorous national training programme. There were no patients with EVD in Israel, but a few suspected cases were assessed. The Israeli plan may provide a template for emergency infectious disease response in other geographically small countries. PMID- 26558846 TI - Femoral Hernias in Patients Undergoing Total Extraperitoneal Laparoscopic Hernia Repair: Including Routine Evaluation of the Femoral Canal in Approaches to Inguinal Hernia Repair. PMID- 26558847 TI - Assessment and characterization of biofilm formation among human isolates of Streptococcus dysgalactiae subsp. equisimilis. AB - The capacity to form biofilm is considered a protective mechanism that allows the bacteria to survive and proliferate in hostile environments, facilitating the maintenance of the infectious process. Recently, biofilm has become a topic of interest in the study of the human pathogen group A Streptococcus (GAS). Although GAS has not been associated with infection on medical implants, the presence of microcolonies embedded in an extracellular matrix on infected tissues has been reported. Despite the similarity between GAS and Streptococcus dysgalactiae subspecies equisimilis (SDSE), there are no studies in the literature describing the production of biofilm by SDSE. In this work, we assessed and characterized biofilm development among SDSE human isolates of group C. The in vitro data showed that 59.3% of the 118 isolates tested were able to form acid-induced biofilm on glass, and 28% formed it on polystyrene surfaces. More importantly, biofilm was also formed in a foreign body model in mice. The biofilm structure was analyzed by confocal laser scanning microscopy, transmission electron microscopy, and scanning electron microscopy. Long fibrillar-like structures were observed by scanning electron microscopy. Additionally, the expression of a pilus associated gene of SDSE was increased for in vitro sessile cells compared with planktonics, and when sessile cells were collected from biofilms formed in the animal model compared with that of in vitro model. Results obtained from the immunofluorescence microscopy indicated the biofilm was immunogenic. Our data also suggested a role for proteins, exopolysaccharide and extracellular DNA in the formation and accumulation of biofilm by SDSE. PMID- 26558848 TI - Arsenic removal from contaminated brackish sea water by sorption onto Al hydroxides and Fe phases mobilized by land-use. AB - This study examines the spatial and temporal distribution patterns of arsenic (As) in solid and aqueous materials along the mixing zone of an estuary, located in the south-eastern part of the Bothnian Bay and fed by a creek running through an acid sulfate (AS) soil landscape. The concentrations of As in solution form (<1 kDa) increase steadily from the creek mouth to the outer estuary, suggesting that inflowing seawater, rather than AS soil, is the major As source in the estuary. In sediments at the outer estuary, As was accumulated and diagenetically cycled in the surficial layers, as throughout much of the Bothnian Bay. In contrast, in sediments in the inner estuary, As concentrations and accumulation rates showed systematical peaks at greater depths. These peaks were overall consistent with the temporal trend of past As discharges from the Ronnskar smelter and the accompanied As concentrations in past sea-water of the Bothnian Bay, pointing to a connection between the historical smelter activities and the sediment-bound As in the inner estuary. However, the concentrations and accumulation rates of As peaked at depths where the smelter activities had already declined, but a large increase in the deposition of Al hydroxides and Fe phases occurred in response to intensified land-use in the mid 1960's and early 1970's. This correspondence suggests that, apart from the inflowing As contaminated seawater, capture by Al hydroxides, Fe hydroxides and Fe-organic complexes is another important factor for As deposition in the inner estuary. After accumulating in the sediment, the solid-phase As was partly remobilized, as reflected by increased pore-water As concentrations, a process favored by As(V) reduction and high concentrations of dissolved organic matter. PMID- 26558850 TI - Proxemics in Couple Interactions: Rekindling an Old Optic. AB - Utilizing as a lens the interpersonal implications of physical interpersonal distances in social contexts (a set of variables present during the professional discourse during the 1960s and 1970s, to then fade away), this article explores interactive process displayed by the protagonic couple in Bela Bartok's opera "Bluebeard Castle," an exercise aimed at underlining the value of maintaining proxemics as an explicit level of observation for clinical practice and interpersonal research. PMID- 26558849 TI - Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival. AB - Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution are also unknown. Thus, we developed 0.1%, 0.2% and 0.5% FTY720 ophthalmic solutions and evaluated their chemical stabilities under various storage conditions with high- performance liquid chromatography. To investigate the ocular irritancy of the FTY720 ophthalmic solution, New Zealand albino rabbits were subjected to the Draize test. Furthermore, classic, well-established rat allogenic penetrating keratoplasty models were used to investigate the anti-rejection efficacy of the tested FTY720 ophthalmic solutions. We found that the non-irritating 0.5% FTY720 ophthalmic solution could prolong corneal allograft survival in rats with significant efficacy for about one month. Furthermore, no significant concentration changes occurred in any of the types of FTY720 ophthalmic solutions within three months. These results revealed crucial profiles of FTY720 ophthalmic solutions and warrant further investigation and optimization of FTY720 in the anti-rejection therapy after keratoplasty. PMID- 26558851 TI - Semi-automated quantitative intravoxel incoherent motion analysis and its implementation in breast diffusion-weighted imaging. AB - BACKGROUND: To optimize and validate intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) compared with the apparent diffusion coefficient (ADC) for semi-automated analysis of breast lesions using a multi-reader setup. MATERIALS AND METHODS: Patients (n = 176) with breast lesions (>=1 cm) and known pathology were prospectively examined (1.5 Tesla) with DWI (b = 0, 50, 200, 500, 800, 1000 s/mm(2) ) between November 2008 and July 2014 and grouped into a training and test set. Three independent readers applied a semi-automated procedure for setting regions-of-interest for each lesion and recorded ADC and IVIM parameters: molecular diffusion (Dslow ), microperfusion (Dfast ), and the fraction of Dfast (ffast ). In the training set (24 lesions, 12 benign), a semi automated method was optimized to yield maximum true negatives (TN) with minimal false negatives (FN): only the optimal fraction (Fo) of voxels in the lesions was used and optimal thresholds were determined. The optimal Fo and thresholds were then applied to a consecutive test set (139 lesions, 23 benign) to obtain specificity and sensitivity. RESULTS: In the training set, optimal thresholds were 1.44 * 10(-3) mm(2) /s (Dslow ), 18.55 * 10(-3) mm(2) /s (Dfast ), 0.247 (ffast ) and 2.00 * 10(-3) mm(2) /s (ADC) with Fo set to 0.61, 0.85, 1.0, and 1.0, respectively, this resulted in TN = 5 (IVIM) and TN = 1 (ADC), with FN = 0. In the test set, sensitivity and specificity among the readers were 90.5-93.1% and 43.5-52.2%, respectively, for IVIM, and 94.8-95.7% and 13.0-21.7% for ADC (P <= 0.0034) without inter-reader differences (P = 1.000). CONCLUSION: The presented semi-automated method for breast lesion evaluation is reader independent and yields significantly higher specificity for IVIM compared with the ADC. PMID- 26558852 TI - The World Health Organization safe surgery checklist as a catalyst for system improvement. PMID- 26558853 TI - Mining the hidden dysrhythmia - can machines get smarter at defining the anaesthetised state? PMID- 26558854 TI - Haematological malignancy and critical care - new bedfellows? PMID- 26558855 TI - Implementation of the WHO Surgical Safety Checklist and surgical swab and instrument counts at a regional referral hospital in Uganda - a quality improvement project. AB - The World Health Organization (WHO) Surgical Safety Checklist is a cost-effective tool that has been shown to improve patient safety. We explored the applicability and effectiveness of quality improvement methodology to implement the WHO checklist and surgical counts at Mbarara Regional Referral Hospital in Uganda between October 2012 and September 2013. Compliance rates were evaluated prospectively and monthly structured feedback sessions were held. Checklist and surgical count compliance rates increased from a baseline median (IQR [range]) of 29.5% (0-63.5 [0-67.0]) to 85.0% (82.8-87.5 [79.0-93.0]) and from 25.5% (0-52.5 [0-60.0]) to 83.0% (80.8-85.5 [69.0-89.0]), respectively. The mean all-or-none completion rate of the checklist was 69.3% (SD 7.7, 95% CI [64.8-73.9]). Use of the checklist was associated with performance of surgical counts (p value < 0.001; r(2) = 0.91). Pareto analysis showed that understaffing, malfunctioning and lack of equipment were the main challenges. A carefully designed quality improvement project, including stepwise incremental change and standardisation of practice, can be an effective way of improving clinical practice in low-income settings. PMID- 26558856 TI - Critical care after lung resection: CALoR 1, a single-centre pilot study. AB - Lung resection is associated with significant perioperative morbidity, and a proportion of patients will require intensive care following surgery. We set out to characterise this population, assess their burden of disease and investigate the influence of anaesthetic and surgical techniques on their admission rate. Over a two-year period, 1169 patients underwent surgery, with 30 patients (2.6%) requiring unplanned intensive care. Patients requiring support had a higher mortality (0.2% vs 26.7%, p < 0.001). Logistic regression (following adjustment for Thoracoscore) revealed that an open surgical approach was associated with higher likelihood of admission (p = 0.025, odds ratio = 5.25). There was also a trend towards increased likelihood of admission in patients who received volatile anaesthesia (p = 0.061, odds ratio = 2.08). This topic has been selected for further investigation as part of the 2015 Association of Cardiothoracic Anaesthetists (ACTA) second national collaborative audit, with this study providing pilot data before a multi-centre study. PMID- 26558857 TI - Design and validation of the Regional Anaesthesia Procedural Skills Assessment Tool. AB - The aim of this study was to create and evaluate the validity, reliability and feasibility of the Regional Anaesthesia Procedural Skills tool, designed for the assessment of all peripheral and neuraxial blocks using all nerve localisation techniques. The first phase was construction of a 25-item checklist by five regional anaesthesia experts using a Delphi process. This checklist was combined with a global rating scale to create the tool. In the second phase, initial validation by 10 independent anaesthetists using a test-retest methodology was successful (Cohen kappa >= 0.70 for inter-rater agreement, scores between test to retest, paired t-test, p > 0.12). In the third phase, 70 clinical videos of trainees were scored by three blinded international assessors. The RAPS tool exhibited face validity (p < 0.026), construct validity (p < 0.001), feasibility (mean time to score < 3.9 min), and overall reliability (intraclass correlation coefficient 0.80 (95% CI 0.67-0.88)). The Regional Anaesthesia Procedural Skills tool used in this study is a valid and reliable assessment tool to score the performance of trainees for regional anaesthesia. PMID- 26558858 TI - A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade. AB - We reviewed systematically sugammadex vs neostigmine for reversing neuromuscular blockade. We included 17 randomised controlled trials with 1553 participants. Sugammadex reduced all signs of residual postoperative paralysis, relative risk (95% CI) 0.46 (0.29-0.71), p = 0.0004 and minor respiratory events, relative risk (95% CI) 0.51 (0.32-0.80), p = 0.0034. There was no difference in critical respiratory events, relative risk (95% CI) 0.13 (0.02-1.06), p = 0.06. Sugammadex reduced drug-related side-effects, relative risk (95% CI) 0.72 (0.54-0.95), p = 0.02. There was no difference in the rate of postoperative nausea or the rate of postoperative vomiting, relative risk (95% CI) 0.94 (0.79-1.13), p = 0.53, and 0.87 (0.65-1.17), p = 0.36 respectively. PMID- 26558859 TI - Further reducing the risk of wrong site block. PMID- 26558860 TI - Consent - more problems than solutions. PMID- 26558861 TI - Consent - implications for day-to-day anaesthetic practice. PMID- 26558862 TI - Paternalism and consent for anaesthesia - a reply. PMID- 26558863 TI - Ethical issues in magnesium/sugammadex study. PMID- 26558864 TI - Magnesium sulphate effects on sugammadex reversal time - a reply. PMID- 26558865 TI - Is prophylactic epidural blood patch the answer? PMID- 26558866 TI - Prophylactic epidural blood patch - a reply. PMID- 26558867 TI - Prioritising emergency laparotomy. PMID- 26558868 TI - Prioritising emergency laparotomy - a reply. PMID- 26558869 TI - Red syringe labelling. PMID- 26558870 TI - Peri-operative risk reduction in obese patients. PMID- 26558871 TI - Magnetic resonance imaging safety of surgical clips and staples. PMID- 26558872 TI - Videolaryngoscopy in trauma. PMID- 26558873 TI - Residual neuromuscular blockade and tracheal extubation in recovery rooms - a reply. PMID- 26558874 TI - NATO phonetic alphabet for medical telecommunication. PMID- 26558875 TI - Litholyme((r)) cost comparison with soda lime. PMID- 26558877 TI - Two molecular measures of relatedness based on haplotype sharing. AB - BACKGROUND: Measuring the extent of shared ancestry between individuals or organisms is important in many fields, including forensic science, conservation genetics and animal breeding. The traditional approach is to calculate the expected degree of relatedness between individuals in a pedigree. This assumes that the founders of the pedigree are non-inbred and unrelated to each other, which is rarely the case. In contrast, molecular data allow measurement of actual relatedness without knowledge of a pedigree. Methods to do this have been proposed, but generally do not take the lengths of the genomic regions shared between individuals into account. RESULTS: Two measures based on the extent of haplotype sharing between genomes are proposed. The intercept measure B estimates the fraction of shared genome between individuals, and the product measure C is closely related to the numerator relationship matrix A. Both are based on a model for the joint distribution of markers at the haplotype level. The two measures are compared to the pedigree-based measure A and to vanRaden's G, a frequently used molecular measure, using a set of data comprising 5037 dairy cattle. The comparison criteria include the ability to capture genealogical relatedness and the prediction accuracy obtained when used in genomic prediction. Both B and C explain around 95 % of the variation in A, whereas G explains around 6 %. G captures genealogical relatedness poorly, particularly for distantly related individuals (second cousins or farther). Both B and C tend to be larger than A but this can be ascribed to the assumption of non-inbred unrelated founders. Using C in linear mixed models results in slightly higher prediction accuracy than G, and using B results in slightly lower prediction accuracy. CONCLUSIONS: The two proposed measures of relatedness capture genealogical relatedness well, outperforming vanRaden's G in this respect. When used in genomic prediction models, the product measure leads to slightly improved prediction accuracy. PMID- 26558878 TI - Influence of Cardiac Function and Loading Conditions on the Myocardial Performance Index - Theoretical Analysis Based on a Mathematical Model. AB - BACKGROUND: The myocardial performance index (MPI) has emerged as a Doppler derived index for global ventricular function capable of estimating combined systolic and diastolic performance. While several studies have reported its load dependency, responses of the MPI to various hemodynamic changes have not been fully characterized. METHODS AND RESULTS: The response characteristics of the MPI were examined and compared with ejection fractions (EF) by changing hemodynamic parameters within the physiological range in a lumped parameter model of the cardiovascular system. At baseline, the MPI was 0.42 and the EF was 0.68. Heart rate increase resulted in a decrease in EF and an increase in the MPI. Reduction in end-systolic elastance decreased EF and increased the MPI. Volume overload and ventricular stiffening did not affect EF but paradoxically reduced the MPI. Increased afterload due to higher systemic resistance resulted in a decrease in EF and increase in the MPI, but afterload increase caused by reduced arterial compliance led to a decrease in both EF and MPI. These MPI characteristics caused paradoxical improvement of the MPI during disease progression of chronic heart failure in a simulation of mitral regurgitation. CONCLUSIONS: The MPI is affected by a wider variety of hemodynamic parameters than EF. In addition, it is predicted to decrease paradoxically with volume overload, reduction in arterial compliance, or ventricular diastolic stiffening. These MPI characteristics should be considered when assessing cardiovascular dynamics using this index. PMID- 26558876 TI - CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. AB - The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non-small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy. PMID- 26558879 TI - Prognostic Impact of Functional Mitral Regurgitation in Patients Admitted With Acute Decompensated Heart Failure. AB - BACKGROUND: Functional mitral regurgitation (FMR) is a common complication of heart failure (HF) and worsens in acute decompensation. It is unclear whether FMR on admission or discharge determines the outcome. This study aimed to elucidate the prognostic significance of FMR on admission or discharge in patients admitted with acute decompensated HF. METHODS AND RESULTS: From 2006 to 2009, 349 patients admitted with acute decompensated HF were enrolled. They were followed with the composite endpoint of all-cause death and hospitalization for HF; 74 (21%) died and 113 (32%) developed the composite endpoint during 2.1+/-1.3 years. Moderate/severe FMR at discharge was associated with the composite endpoint (P=0.001), whereas that on admission was not. Multivariate Cox proportional hazard analysis showed that moderate/severe FMR (hazard ratio [95% confidence interval] =1.70 [1.03-2.73] P=0.04), logBNP, and NYHA class III/IV at discharge were independent determinants of the outcome. Moderate/severe FMR at discharge with BNP >=200 pg/ml was prognostic, but BNP <200 pg/ml was no longer prognostic. CONCLUSIONS: Residual moderate/severe FMR after medical therapy for acute decompensated HF was associated with poor outcome, suggesting a potential target for further treatment of HF. PMID- 26558880 TI - A comprehensive list of asthmagens to inform health interventions in the Australian workplace. AB - OBJECTIVE: To develop a comprehensive list of asthmagens which may occur in occupational settings in Australia. METHODS: Potential asthmagens considered for this list were identified through work health and safety classification databases in Australia and through lists developed by professional associations in other countries. Inclusion criteria were: there is evidence that the agent is asthmagenic; it is used in occupational settings; and it is available in Australia. RESULTS: The final list contained 277 asthmagens in 27 groups that may be found in occupational circumstances in Australia. Three other agents that have been documented as asthmagens in Australia were included: almond dust, fluoride (in aluminium pot room fumes); and sawdust from the Australian Blackwood. CONCLUSIONS: This is the first comprehensive and inclusive list of Australian occupationally relevant asthmagens to have been compiled. IMPLICATIONS: This list is specific for Australian workplace exposure to asthmagens. It will help focus policy and preventative practices and reduce the burden of occupational asthma. It will also be useful in future studies to identify those who are exposed to the asthmagens and provide information to assist regulators to identify industries, occupations, specific activities and existing exposure standards that can be targeted to improve worker health and welfare. PMID- 26558881 TI - Mussel-Inspired Materials: Self-Healing through Coordination Chemistry. AB - Improved understanding of the underwater attachment strategy of the blue mussels and other marine organisms has inspired researchers to find new routes to advanced materials. Mussels use polyphenols, such as the catechol-containing amino acid 3,4-dihydroxyphenylalanine (DOPA), to attach to surfaces. Catechols and their analogues can undergo both oxidative covalent cross-linking under alkaline conditions and take part in coordination chemistry. The former has resulted in the widespread use of polydopamine and related materials. The latter is emerging as a tool to make self-healing materials due to the reversible nature of coordination bonds. We review how mussel-inspired materials have been made with a focus on the less developed use of metal coordination and illustrate how this chemistry can be widely to make self-healing materials. PMID- 26558882 TI - Intangible and Economic Impacts of Hendra Virus Prevention Strategies. AB - Hendra virus (HeV), a potentially fatal zoonotic disease spread by flying foxes, to date has always infected humans via a spillover event from equine HeV infection. In a theoretical case study, we compared the impacts of two different HeV prevention strategies - vaccination and flying fox roost removal - using a recently developed framework that considers different stakeholder group perspectives. The perspectives of the four selected stakeholder groups regarding intangibles were inferred from public discussions and coverage in the media. For all stakeholder groups, the option to vaccinate horses was found to add value to the economic results when the intangible impacts were included in the analysis, while the option for roost removal unanimously detracted from economic analysis value when the intangible impacts were included. Both the mean and median stakeholder-adjusted value ratios (2.25 and 2.12, respectively) for vaccination were inflated when intangible impacts were included, by value-adding to the results of a traditional economic analysis. In the roost removal strategy, these ratios (1.19 and 1.16, respectively) were deflated when intangible impacts were included. Results of this theoretical study suggest that the inclusion of intangible impacts promotes the value of a two-dose initial vaccination protocol using a subunit vaccination considered to offer complete protection for horses, as a strategy to control HeV, whereas roost removal becomes an even more costly strategy. Outcome of the analysis is particularly sensitive to the intangible value placed on human health. Further evaluation - via sociological methods - of values placed on intangibles by various stakeholder groups is warranted. PMID- 26558883 TI - You need to see the world in order to measure it: The importance of a high follow up rate. PMID- 26558884 TI - Vascular high ligation and embryological plane dissection in laparoscopic restorative proctocolectomy for ulcerative colitis - a video vignette. PMID- 26558885 TI - Spoonful of sugar: Improving the palatability of emergency department visits for children and their families. PMID- 26558886 TI - Remyelination in multiple sclerosis: realizing a long-standing challenge. AB - Multiple sclerosis (MS) is a multifaceted disease, in which an inflammatory autoimmune attack on the myelin in the central nervous system (CNS) leads to extensive demyelination and subsequent axonal pathology. The challenge for MS therapy is to combine effective immunomodulatory therapies with novel neuroprotective approaches that promote repair, in particular remyelination, beyond its limited spontaneous extent. Cumulative findings indicate that immunomodulatory treatments can induce neuroprotective outcomes and provide a supportive milieu for repair processes. Growing understanding of MS pathology together with biotechnological advances has resulted in promising strategies such as inhibitory molecules, monoclonal antibodies and cell therapies. Several candidates that have shown significant effects on the oligodendrocyte population and/or myelin synthesis in animal models are currently or soon to be tested in clinical trials. PMID- 26558887 TI - Molecular Rift: Virtual Reality for Drug Designers. AB - Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub. PMID- 26558888 TI - Laser-Limited Signatures of Quantum Coherence. AB - Quantum coherence is proclaimed to promote efficient energy collection by light harvesting complexes and prototype organic photovoltaics. However, supporting spectroscopic studies are hindered by the problem of distinguishing between the excited state and ground state origin of coherent spectral transients. Coherence amplitude maps, which systematically represent quantum beats observable in two dimensional (2D) spectroscopy, are currently the prevalent tool for making this distinction. In this article, we present coherence amplitude maps of a molecular dimer, which have become significantly distorted as a result of the finite laser bandwidth used to record the 2D spectra. We argue that under standard spectroscopic conditions similar distortions are to be expected for compounds absorbing over a spectral range similar to, or exceeding, that of the dimer. These include virtually all photovoltaic polymers and certain photosynthetic complexes. With the distortion of coherence amplitude maps, alternative ways to identify quantum coherence are called for. Here, we use numerical simulations that reproduce the essential photophysics of the dimer to unambiguously determine the excited state origin of prominent quantum beats observed in the 2D spectral measurements. This approach is proposed as a dependable method for coherence identification. PMID- 26558889 TI - Synthesis of (Homooxa)calixarene-Monoquinones through the "All-but-One" Methodology. AB - The iteroselective "all-but-one" carbamatation methodology has been successfully extended to homooxacalixarenes and used for the selective and controlled synthesis of homooxacalixarene-monoquinones and calixarene-monoquinones. These moquinone derivatives constitute interesting molecular platforms that, until now, were inaccessible through any efficient means. PMID- 26558890 TI - Decreased risk of hypertension in subjects with skin cancers - another salubrious effect of sunlight? PMID- 26558891 TI - The contrasting nature of woody plant species in different neotropical forest biomes reflects differences in ecological stability. AB - A fundamental premise of this review is that distinctive phylogenetic and biogeographic patterns in clades endemic to different major biomes illuminate the evolutionary process. In seasonally dry tropical forests (SDTFs), phylogenies are geographically structured and multiple individuals representing single species coalesce. This pattern of monophyletic species, coupled with their old species stem ages, is indicative of maintenance of small effective population sizes over evolutionary timescales, which suggests that SDTF is difficult to immigrate into because of persistent resident lineages adapted to a stable, seasonally dry ecology. By contrast, lack of coalescence in conspecific accessions of abundant and often widespread species is more frequent in rain forests and is likely to reflect large effective population sizes maintained over huge areas by effective seed and pollen flow. Species nonmonophyly, young species stem ages and lack of geographical structure in rain forest phylogenies may reflect more widespread disturbance by drought and landscape evolution causing resident mortality that opens up greater opportunities for immigration and speciation. We recommend full species sampling and inclusion of multiple accessions representing individual species in phylogenies to highlight nonmonophyletic species, which we predict will be frequent in rain forest and savanna, and which represent excellent case studies of incipient speciation. PMID- 26558893 TI - Correction: MATtrack: A MATLAB-Based Quantitative Image Analysis Platform for Investigating Real-Time Photo-Converted Fluorescent Signals in Live Cells. PMID- 26558892 TI - Discovery in Droplets. PMID- 26558894 TI - The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish. AB - We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID- 26558896 TI - Resource Limitation, Controphic Ostracod Density and Larval Mosquito Development. AB - Aquatic environments can be restricted with the amount of available food resources especially with changes to both abiotic and biotic conditions. Mosquito larvae, in particular, are sensitive to changes in food resources. Resource limitation through inter-, and intra-specific competition among mosquitoes are known to affect both their development and survival. However, much less is understood about the effects of non-culicid controphic competitors (species that share the same trophic level). To address this knowledge gap, we investigated and compared mosquito larval development, survival and adult size in two experiments, one with different densities of non-culicid controphic conditions and the other with altered resource conditions. We used Aedes camptorhynchus, a salt marsh breeding mosquito and a prominent vector for Ross River virus in Australia. Aedes camptorhynchus usually has few competitors due to its halo-tolerance and distribution in salt marshes. However, sympatric ostracod micro-crustaceans often co-occur within these salt marshes and can be found in dense populations, with field evidence suggesting exploitative competition for resources. Our experiments demonstrate resource limiting conditions caused significant increases in mosquito developmental times, decreased adult survival and decreased adult size. Overall, non-culicid exploitation experiments showed little effect on larval development and survival, but similar effects on adult size. We suggest that the alterations of adult traits owing to non-culicid controphic competition has potential to extend to vector-borne disease transmission. PMID- 26558895 TI - Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries. AB - Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability. PMID- 26558897 TI - Toxicity of Carboxylic Acid-Containing Drugs: The Role of Acyl Migration and CoA Conjugation Investigated. AB - Many carboxylic acid-containing drugs are associated with idiosyncratic drug toxicity (IDT), which may be caused by reactive acyl glucuronide metabolites. The rate of acyl migration has been earlier suggested as a predictor of acyl glucuronide reactivity. Additionally, acyl Coenzyme A (CoA) conjugates are known to be reactive. Here, 13 drugs with a carboxylic acid moiety were incubated with human liver microsomes to produce acyl glucuronide conjugates for the determination of acyl glucuronide half-lives by acyl migration and with HepaRG cells to monitor the formation of acyl CoA conjugates, their further conjugate metabolites, and trans-acylation products with glutathione. Additionally, in vitro cytotoxicity and mitochondrial toxicity experiments were performed with HepaRG cells to compare the predictability of toxicity. Clearly, longer acyl glucuronide half-lives were observed for safe drugs compared to drugs that can cause IDT. Correlation between half-lives and toxicity classification increased when "relative half-lives," taking into account the formation of isomeric AG forms due to acyl migration and eliminating the effect of hydrolysis, were used instead of plain disappearance of the initial 1-O-beta-AG-form. Correlation was improved further when a daily dose of the drug was taken into account. CoA and related conjugates were detected primarily for the drugs that have the capability to cause IDT, although some exceptions to this were observed. Cytotoxicity and mitochondrial toxicity did not correlate to drug safety. On the basis of the results, the short relative half-life of the acyl glucuronide (high acyl migration rate), high daily dose and detection of acyl CoA conjugates, or further metabolites derived from acyl CoA together seem to indicate that carboxylic acid containing drugs have a higher probability to cause drug-induced liver injury (DILI). PMID- 26558898 TI - Polypill treatments for cardiovascular diseases. AB - Cardiovascular disease (CVD) is the leading cause of mortality globally. Effective CVD preventive medications are available including statin, blood pressure-lowering and antiplatelet medications; however most people do not take these drugs long term. Fixed-dose combination pills ("polypills") have been shown, in several clinical trials, to improve adherence to these recommended medications, with corresponding improvements in risk factors such as blood pressure and LDL-cholesterol. In patients not taking all modalities of recommended CVD preventive therapies, polypill-based strategies could importantly contribute to global CVD control strategies. The largest benefits are seen in those who are under-treated at baseline, rather than those who are already taking the individual components separately: simplified step-up is more important than pill count reduction. Despite the potential benefits for patients and payers, only a few polypills are available due to market failure in the funding of research and development for affordable non-communicable disease medicines. Regulatory paradigms have focused on substitution indications among patients already taking component medications; however, this is the population that is likely to receive the least benefit from a polypill-based strategy. Greater health impact is likely if focus is given to patients who have indications for all polypill components, but currently do not receive the benefits of recommended medicines long term. PMID- 26558899 TI - Effect of fish oil supplement in maintenance hemodialysis patients: a systematic review and meta-analysis of published randomized controlled trials. AB - PURPOSE: The purpose of this study was to systematically assess the efficacy of fish oil therapy on maintenance hemodialysis patients (MHD). METHODS: Electronic databases, including PubMed, Cochrane library, EMBase, and Web of Science, were searched for randomized controlled trials (RCTs) of fish oil versus placebo or no treatment in MHD patients. The study selection and data extraction were conducted independently by two reviewers, and statistical analysis was performed using RevMan software, version 5.2. RESULTS: A total of thirteen eligible RCTs involving 916 subjects (461 in the experimental group and 455 in the control group) were included. The meta-analysis showed that fish oil significantly reduced arteriovenous graft (AV-graft) events [risk ratio (RR) 0.71, 95 % confidence interval (CI) were (0.52, 0.97)] and cardiovascular events [RR (95 %CI) were 0.41 (0.26, 0.66)] in the fish oil group. In addition, compared with the control group, fish oil significantly decreased the Beck Depression Inventory (BDI) score [weighted mean difference (WMD) (95 %CI) were -11.91 (-15.88, 7.95)], serum intact parathyroidism (iPTH), C-reactive protein (CRP), and triglycerides (TG) [standard mean difference (SMD) (95 %CI) were -0.56 (-0.89, 0.23); -0.36 (-0.63, -0.09), and -0.41 (-0.68, -0.14), respectively]. However, the fish oil group did not differ significantly from the control group in albumin (ALB), hemoglobin (Hb), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and mortality. CONCLUSIONS: Fish oil reduced the risk of AV-graft events and cardiovascular events, and alleviated depression symptoms in MHD patients. It can also improve secondary hyperparathyroidism, micro-inflammation, and hypertriglyceridemia. But there is no evidence that fish oil can improve nutritional status and renal anemia. PMID- 26558901 TI - Bonn eXperimental System (BoXS): An open-source platform for interactive experiments in psychology and economics. AB - The increased interest in complex-interactive behavior on the one hand and the cognitive and affective processes underlying behavior on the other are a challenge for researchers in psychology and behavioral economics. Research often necessitates that participants strategically interact with each other in dyads or groups. At the same time, to investigate the underlying cognitive and affective processes in a fine-grained manner, not only choices but also other variables such as decision time, information search, and pupil dilation should be recorded. The Bonn eXperimental System (BoXS) introduced in this article is an open-source platform that allows interactive as well as non-interactive experiments to be conducted while recording process measures very efficiently and completely browser-based. In the current version, BoXS has particularly been extended to enable conducting interactive eye-tracking and mouse-tracking experiments. One core advantage of BoXS is its simplicity. Using BoXS does not require prior installation for both experimenters and participants, which allows for running studies outside the laboratory and over the internet. Learning to program for BoXS is easy even for researchers without previous programming experience. PMID- 26558902 TI - The sensitivity and specificity of a diagnostic test of sequence-space synesthesia. AB - People with sequence-space synesthesia (SSS) report stable visuo-spatial forms corresponding to numbers, days, and months (amongst others). This type of synesthesia has intrigued scientists for over 130 years but the lack of an agreed upon tool for assessing it has held back research on this phenomenon. The present study builds on previous tests by measuring the consistency of spatial locations that is known to discriminate controls from synesthetes. We document, for the first time, the sensitivity and specificity of such a test and suggest a diagnostic cut-off point for discriminating between the groups based on the area bounded by different placement attempts with the same item. PMID- 26558900 TI - Development of Risk Score for Predicting 3-Year Incidence of Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study. AB - OBJECTIVE: Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population. METHODS: Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008-2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) >= 126 mg/dl, random plasma glucose >= 200 mg/dl, glycated hemoglobin (HbA1c) >= 6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort. RESULTS: The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703-0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883-0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715 0.753) and 0.882 (0.868-0.895), respectively. Participants with a non-invasive score of >= 15 and invasive score of >= 19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years. CONCLUSIONS: The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c. PMID- 26558903 TI - Efficient In Silico Identification of a Common Insertion in the MAK Gene which Causes Retinitis Pigmentosa. AB - BACKGROUND: Next generation sequencing (NGS) offers a rapid and comprehensive method of screening for mutations associated with retinitis pigmentosa and related disorders. However, certain sequence alterations such as large insertions or deletions may remain undetected using standard NGS pipelines. One such mutation is a recently-identified Alu insertion into the Male Germ Cell Associated Kinase (MAK) gene, which is missed by standard NGS-based variant callers. Here, we developed an in silico method of searching NGS raw sequence reads to detect this mutation, without the need to recalculate sequence alignments or to screen every sample by PCR. METHODS: The Linux program grep was used to search for a 23 bp "probe" sequence containing the known junction sequence of the insert. A corresponding search was performed with the wildtype sequence. The matching reads were counted and further compared to the known sequences of the full wildtype and mutant genomic loci. (See https://github.com/MEEIBioinformaticsCenter/grepsearch.). RESULTS: In a test sample set consisting of eleven previously published homozygous mutants, detection of the MAK-Alu insertion was validated with 100% sensitivity and specificity. As a discovery cohort, raw NGS reads from 1,847 samples (including custom and whole exome selective capture) were searched in ~1 hour on a local computer cluster, yielding an additional five samples with MAK-Alu insertions and solving two previously unsolved pedigrees. Of these, one patient was homozygous for the insertion, one compound heterozygous with a missense change on the other allele (c. 46G>A; p.Gly16Arg), and three were heterozygous carriers. CONCLUSIONS: Using the MAK-Alu grep program proved to be a rapid and effective method of finding a known, disease-causing Alu insertion in a large cohort of patients with NGS data. This simple approach avoids wet-lab assays or computationally expensive algorithms, and could also be used for other known disease-causing insertions and deletions. PMID- 26558904 TI - Cancer Cell Analyses at the Single Cell-Level Using Electroactive Microwell Array Device. AB - Circulating tumor cells (CTCs), shed from primary tumors and disseminated into peripheral blood, are playing a major role in metastasis. Even after isolation of CTCs from blood, the target cells are mixed with a population of other cell types. Here, we propose a new method for analyses of cell mixture at the single cell level using a microfluidic device that contains arrayed electroactive microwells. Dielectrophoretic (DEP) force, induced by the electrodes patterned on the bottom surface of the microwells, allows efficient trapping and stable positioning of single cells for high-throughput biochemical analyses. We demonstrated that various on-chip analyses including immunostaining, viability/apoptosis assay and fluorescent in situ hybridization (FISH) at the single-cell level could be conducted just by applying specific reagents for each assay. Our simple method should greatly help discrimination and analysis of rare cancer cells among a population of blood cells. PMID- 26558906 TI - [Catheter ablation and the complications]. AB - Catheter ablation of atrial fibrillation has developed into a standard therapy and even in some cases as a first line therapy. This has resulted in a clear increase in the number of procedures in recent years. The published data from experienced centers indicate that the number of complications decreases with increasing experience; however, due to the parallel increase in the number of inexperienced centers, the average complication rate shows a tendency to increase. In the long term this necessitates a reliable quality assurance in order not to leave the choice of the "safe centers" up to the patient. Vascular complications are the most common, which in most cases have an uneventful course and do not necessitate further interventions. Particularly the incidence of ischemic stroke can be well-countered by strict control of periprocedural anticoagulation. The frequency of occurrence of phrenic nerve lesions, which are more common when selecting cryoenergy, can be reduced by stimulation of the phrenic nerve during ablation of the right pulmonary vein. The most feared complication of an atrioesophageal fistula is rare. No data for an effective avoidance of complications are available. A postprocedural therapy with proton pump inhibitors for 4-6 weeks, the intraprocedural measurement of esophageal temperature and reduction of the ablation energy on the posterior wall of the left atrium can possible help to reduce the frequency of complications. PMID- 26558905 TI - The Seroprevalence of Hepatitis C Antibodies in Immigrants and Refugees from Intermediate and High Endemic Countries: A Systematic Review and Meta-Analysis. AB - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a significant global health issue that leads to 350,000 preventable deaths annually due to associated cirrhosis and hepatocellular carcinoma (HCC). Immigrants and refugees (migrants) originating from intermediate/high HCV endemic countries are likely at increased risk for HCV infection due to HCV exposure in their countries of origin. The aim of this study was to estimate the HCV seroprevalence of the migrant population living in low HCV prevalence countries. METHODS: Four electronic databases were searched from database inception until June 17, 2014 for studies reporting the prevalence of HCV antibodies among migrants. Seroprevalence estimates were pooled with a random-effect model and were stratified by age group, region of origin and migration status and a meta-regression was modeled to explore heterogeneity. RESULTS: Data from 50 studies representing 38,635 migrants from all world regions were included. The overall anti-HCV prevalence (representing previous and current infections) was 1.9% (95% CI, 1.4-2.7%, I2 96.1). Older age and region of origin, particularly Sub-Saharan Africa, Asia, and Eastern Europe were the strongest predictors of HCV seroprevalence. The estimated HCV seroprevalence of migrants from these regions was >2% and is higher than that reported for most host populations. CONCLUSION: Adult migrants originating from Asia, Sub-Saharan Africa and Eastern Europe are at increased risk for HCV and may benefit from targeted HCV screening. PMID- 26558907 TI - [AV nodal reentrant tachycardia. Diagnosis and therapy]. AB - The AV nodal reentrant tachycardia (AVNRT) is one of the most common arrhythmias encountered in clinical practice. It is characterized by a constant heart rate and an on/off phenomenon. The clinical symptoms may include palpitations, anxiety, polyuria, and dyspnea. Typically, tachycardia may be disrupted by vagal maneuvers in many patients. First-line treatment of symptomatic AVNRT is radiofrequency ablation. The present article deals with the characteristics, differential diagnosis and treatment of AVNRT in the EP lab. It is the second part of a series of manuscripts which may facilitate further education in the specific field of electrophysiology. PMID- 26558908 TI - In vitro and in vivo sustained release of exenatide from vesicular phospholipid gels for type II diabetes. AB - Diabetes is a chronic disease that requires daily treatment to maintain a stable blood glucose level. Sustained-release formulations can thus benefit the treatment of diabetes by reducing the repeated administration of therapeutics. Our study aimed to develop a sustained-release platform for exenatide that is biocompatible and capable of mass production. Vesicular phospholipid gels (VPGs) are semisolid phospholipid dispersions with controlled release profiles. Exenatide-VPGs prepared via simple magnetic stirring showed excellent biocompatibility with an average particle size of about 15 MUm after redispersion. VPGs were shown to achieve sustained release for up to 21 days in vitro with no obvious burst effect. The in vivo release study showed that VPGs sustained the release of the exenatide for up to 11 days. Moreover, after subcutaneous injection of the exenatide-VPGs in the diabetic rats, the hypoglycemic effect lasted for 10 days compared with exenatide solution. In sum, the exenatide-VPGs system represents a promising sustained-release formulation for exenatide with a long-acting therapeutic efficacy in vivo. PMID- 26558909 TI - Covered stents in cervical anastomoses following esophagectomy. AB - INTRODUCTION: Anastomotic complications after esophagectomy are relatively frequent. The off-label use of self-expanding covered metal stents has been shown to be an effective initial treatment for leaks, but there is a paucity of literature regarding their use in cervical esophagogastric anastomoses. We reviewed our outcomes with anastomotic stenting after esophagectomy with cervical esophagogastric reconstruction. METHODS: All stents placed across cervical anastomoses following esophagectomy from 2004 to 2014 were retrospectively reviewed. Indications for surgery and stent placement were collected. For patients with serial stents, each stent event was evaluated separately and as part of its series. Success was defined as resolution of indicated anastomotic problem for at least 90 days. Complications were defined as development of stent related problems. RESULTS: Twenty-three patients had a total of 63 stents placed (16 % prophylactic, 38 % leak, 46 % stricture). Sixty percent of patients had successful resolution of their initial anastomotic problem; 67 % required more than one stent. Strictures and leaks healed in 27 and 70 % of patients, respectively, at a median of 55.5 days. Stent-related complications occurred in 78 % of patients. Complications (per stent event) included 62 % migration, 11 % clinically significant tissue overgrowth, 8 % minor erosion (ulcers), and 8 % major erosion. Stents placed for stricture were more likely to result in complications, especially migration (76.7 vs. 48.5 %, p = 0.02). Preoperative chemoradiation was a significant risk factor for erosion (22.5 vs. 4.3 %, p = 0.05), but not for overall complications. Patients with major erosions had longer stent duration compared to those without (92 vs. 36 days, p = 0.14). DISCUSSION: Although stents are effective at controlling post-esophagectomy anastomotic leaks, they are not effective for treating strictures. Stents have high complication rates, but most are minor. Chemoradiation is a risk factor for stent erosion. Caution should be used when stent duration exceeds 2-3 months due to the risk of erosion. PMID- 26558910 TI - Closing the gap between the laparoscopic and open approaches to abdominal wall hernia repair: a trend and outcomes analysis of the ACS-NSQIP database. AB - OBJECTIVE: To assess trends in utilization and perioperative outcomes of laparoscopic and open abdominal wall hernia repair. METHODS: Using the ACS-NSQIP database between 2009 and 2012, patients were identified as having an ICD-9 diagnosis of an umbilical, ventral, or incisional hernia as well as a CPT code for a laparoscopic or open abdominal wall hernia repair. A coarsened exact matching procedure was utilized to create a matched cohort to mitigate selection bias. Thirty-day outcomes analysis was done for the aggregate and matched cohorts. Subcategory analysis was performed for inpatient/outpatient status, strangulated/incarcerated hernias, initial/recurrent repairs, and hernia type (umbilical, ventral, incisional). Chi-square analysis was performed to determine the statistical significance of each comparison. RESULTS: In total, 112,074 qualifying patients were identified, 86,566 (77.24 %) open and 25,508 (22.76 %) laparoscopic. Patients undergoing laparoscopic repair were more likely to have preexisting comorbidities, but less likely to experience any postoperative morbidity (11.74 vs. 7.25 %, P < 0.0001), serious morbidity (4.55 vs. 3.02 %, P < 0.0001), or mortality (0.36 vs. 0.24 %, P = 0.0030). Creation of the matched cohort produced 17,394 patients in both the laparoscopic and open groups and resulted in a loss of advantage for the laparoscopic approach in terms of morbidity associated with umbilical hernia repairs (P = 0.0082 vs. P = 0.3172). Patients undergoing laparoscopic repair were still less likely to experience any postoperative (9.57 vs. 4.92 %, P < 0.0001) or serious morbidity (3.37 vs. 1.70 %, P < 0.0001). Hospital length of stay in the matched cohort supported initial primary repairs done by an open approach. CONCLUSION: The laparoscopic approach is used in a minority of abdominal wall hernia repairs, though utilization increased by 40 % from 2009 to 2012. The laparoscopic approach continues to be safer on many fronts, but not all, and is arguably not better for umbilical or primary hernia repairs on the basis of overall morbidity and length of stay. PMID- 26558911 TI - Laparoscopic repair of a left-sided paraduodenal hernia. AB - INTRODUCTION: Internal hernias are a rare cause of bowel obstruction, constituting 0.2-0.9 % of all cases with paraduodenal hernias (PDH) being the most common accounting for 50 % of all internal hernias with 75 % of those being left-sided [1, 2]. They are due to small bowel herniating into a peritoneum-lined sac at the fourth portion of the duodenum as the result of abnormal midgut rotation during embryonic development. Patients may present with symptoms of small bowel obstruction, though the majority are found incidentally [3]. Diagnosis is aided with computed tomography (CT) with findings of encapsulated clustering of small bowel loops in the left upper quadrant, bowel between the stomach and pancreas, crowding of mesenteric vessels, and displacement of the inferior mesenteric vein [4]. METHODS: A 34-year-old male presented with a 3-year history of postprandial epigastric pain. After multiple inconclusive imaging studies, he was taken to the operating room for diagnostic laparoscopy. The transverse colon was retracted cephalad, and the distal bowel could be seen entering a defect just lateral to the fourth portion of the duodenum. This mass of herniated bowel was readily reduced, and the defect could be appreciated as a 4-cm invagination lateral to the duodenum and posterior to the inferior mesenteric vein. The defect was then closed using interrupted silk suture and the port sites closed. RESULTS: The patient tolerated the procedure well and was discharged home 24 h later. At 12 months postoperatively, he continued to have intermittent nausea and abdominal pain. Repeated imaging studies including CT scans were negative for obstruction or internal hernia. CONCLUSIONS: PDH are a rare form of internal hernia that result from abnormal midgut rotation during fetal development. Diagnosis is challenging but may be aided by CT imaging. Laparoscopic repair is a safe and effective method of management in these patients [5, 6]. In patients presenting with nausea, vomiting, abdominal pain, and radiographic evidence of PDH, laparoscopic repair should be considered given its safety and efficacy profile. Although surgical intervention did not result in complete resolution of our patient's symptoms, repair of his hernia removed this diagnosis from his differential and facilitated his ultimate diagnosis of functional abdominal pain syndrome. PMID- 26558912 TI - Capsule Commentary on Scales et al., Unintentional Continuation of Medications Intended for Acute Illness After Hospital Discharge: A Population-Based Cohort Study. PMID- 26558913 TI - Hemagglutinin protease secreted by V. cholerae induced apoptosis in breast cancer cells by ROS mediated intrinsic pathway and regresses tumor growth in mice model. AB - Conventional anticancer therapies are effective but have side effects, so alternative targets are being developed. Bacterial toxins that can kill cells or alter the cellular processes like proliferation, apoptosis and differentiation have been reported for cancer treatment. In this study we have shown antitumor activity of hemagglutinin protease (HAP) secreted by Vibrio cholerae. One ug of HAP showed potent antitumor activity when injected into Ehrlich ascites carcinoma (EAC) tumors in Swiss albino mice. Weekly administration of this dose is able to significantly diminish a large tumor volume within 3 weeks and increases the survival rates of cancerous mice. HAP showed apoptotic activity on EAC and other malignant cells. Increased level of pro-apoptotic p53 with increased ratio of pro apoptotic Bax to anti-apoptotic Bcl-2 signify that HAP induced apoptogenic signals lead to death of the tumor cells. In vivo and ex vivo studies suggest that mitochondrial dependent intrinsic pathway is responsible for this apoptosis. The level of ROS in malignant cells is reported to be higher than the normal healthy cells. HAP induces oxidative stress and increases the level of ROS in malignant cells which is significantly higher than the normal healthy cells. As a result the malignant cells cross the threshold level of ROS for cell survival faster than normal healthy cells. This mechanism causes HAP mediated apoptosis in malignant cells, but normal cells remain unaltered in the same environment. Our study suggests that HAP may be used as a new candidate drug for cancer therapy. PMID- 26558914 TI - A Rare Skin Disorder Misdiagnosed as Juvenile Idiopathic Arthritis. PMID- 26558915 TI - Antibiotic Susceptibility and Molecular Characterization of Campylobacter jejuni Strain Isolated from a Guillain Barre Syndrome Child. PMID- 26558916 TI - Severe ABO Hemolytic Disease of Newborn with High Maternal Antibody Titres in a Direct Antiglobulin Test Negative Neonate. PMID- 26558917 TI - Clinical Profile and Outcome of Serratia Infection among Neonates. PMID- 26558918 TI - Long-Term Prognosis of Patients with Esophageal Atresia and/or Tracheoesophageal Fistula. AB - OBJECTIVE: To investigate long-term prognosis of infants with esophageal atresia (EA) and/or tracheoesophageal fistula (TEF). METHODS: The data of patients with EA were investigated from their medical files. For the neurodevelopmental evaluation, they were requested to come for a return visit to authors' polyclinic. Intellectual development was assessed by Ankara Developmental Screening Inventory (ADSI) (for 0-6 age) and Wechsler Intelligence Scale for Children-Revised (WISC-R) (for 6-16 age). RESULTS: Of the 57 patients, 50 had EA+ distal TEF (87.7 %), six had isolated EA (10.5 %) and one had isolated TEF (1.8 %). Of the total patients, 18 cases (31 %) died and remaining 39 cases (69 %) survived. In the surviving cases, the most common long-term complication was dysphagia (n = 37, 94.8 %). Intellectual levels of the 24 patients assessed by ADSI were normal and of the remaining 15 cases evaluated by WISC-R ranged between 95 and 110 points. CONCLUSIONS: The long-term complications and hospital visits are common in surviving cases of EA; however, they have normal cognitive functions and physical developmental characteristics. PMID- 26558919 TI - Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children. AB - OBJECTIVES: To assess iodine and iron nutritional status among Nepalese school children. METHODS: A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. RESULTS: The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 +/- 1.85 g/dl, 70.45 +/- 34.46 MUg/dl, 386.48 +/- 62.48 MUg/dl, 19.94 +/- 12.07 % and 274.67 MUg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion <100 MUg/L) were present in 34.5 %, 43.4 % and 12.6 % children respectively. Insufficient urinary iodine excretion (urinary iodine excretion <100 MUg/L) was common in anemic and iron deficient children. CONCLUSIONS: Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia. PMID- 26558920 TI - Tremors Following Blood Transfusion in Children with Megaloblastic Anemia. PMID- 26558921 TI - Acneiform Lesion: Importance of Detailed Skin Examination. PMID- 26558922 TI - GMC should be relicensing doctors, not revalidating specialists. PMID- 26558923 TI - Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome. AB - INTRODUCTION: Irritable bowel syndrome diarrhea predominant (IBS-D) is a highly prevalent GI disease, affecting nearly a third of all patients diagnosed with irritable bowel syndrome. Current treatment options are limited. AREAS COVERED: This review discusses the pharmacotherapeutic options for IBS-D including currently used medications, the two newly FDA approved medications, as well as emerging therapies with potential benefit in IBS-D. Particular emphasis is placed on rifaximin and eluxadoline and their possible use in IBS-D. EXPERT OPINION: Current pharmacological treatment of IBS-D includes loperamide, bile acid sequestrants, antispasmodics, tricyclic antidepressants, alosetron, eluxadoline and rifaximin. The latter two treatments have significantly added to the pharmacotherapeutic options for patients suffering from IBS-D. PMID- 26558924 TI - Characterizing patients with psoriasis on injectable biologics adalimumab, etanercept, and ustekinumab: A chart review study. AB - OBJECTIVE: This study examined plaque psoriasis (PsO) patient characteristics across injectable biologics. METHODS: Data were collected from 400 US dermatologists randomly selecting five charts each for patients with PsO (patient n = 2000): adalimumab (ADA; n = 447), etanercept (ETA; 539), ustekinumab (UST) 45 mg (511) and UST 90 mg (503). Physicians had to have been in practice 2 30 years, managing 10+ patients (5 + with biologics for PsO). Generalized estimating equation models, weighted according to inverse probability of patient selection and accounting for patient correlation within physicians, examined patient measures as a function of treatment (UST 90 mg = reference). RESULTS: Patients on UST 90 mg had higher odds of weighing >100 kg (adjusted mean = 34.4%) vs. ADA (10.9%), ETA (5.5%) or UST 45 mg (6.8%), greater body surface affected and higher odds of severe PsO prior to treatment and higher odds of prior biologics use. Mean prior biologics used was higher with UST 90 mg versus ADA or ETA. Number of comorbidities was higher with UST 90 mg versus ETA or UST 45 mg. CONCLUSIONS: Among biologics-treated patients with PsO, UST 90 mg appears to be used in patients with greater weight, baseline severity and prior biologics experience than ADA, ETA or UST 45 mg. UST 90 mg is used in patients with more comorbidities than other treatments except ADA. PMID- 26558926 TI - [Trends in medicine]. PMID- 26558927 TI - [CME: Radioactive iodine therapy in thyroid cancer]. AB - Differentiated thyroid carcinomas represent about 90% of all thyroid tumors and are divided in papillary and follicular carcinomas. Their prognosis is good, however, recurrences are not rare. Their ability to accumulate iodine is used for the radioactive iodine treatment. The aim of the postoperative radioactive iodine ablation therapy is the complete elimination of remnant thyroid cells and sensitive staging (Fig. 1). The recurrence rate decreases after a complete thyroid ablation. Furthermore, thyroglobulin can be used as a sensitive tumor marker. Radioactive iodine treatment by itself describes the therapy of metastases. An exception is the papillary microcarcinoma, which in general is treated by a lobectomy alone. PMID- 26558929 TI - [What is your diagnosis?]. PMID- 26558930 TI - [Trends in family medicine--how to sort the wheat from the chaff]. AB - Considering the trends in medicine, time just seems to move at a slower pace in general practice/family medicine than in the medical specialties. Novel medical drugs and therapeutic modalities appear to take longer to become well established, and sometimes it never happens. There are obvious gaps between the requirements of the guidelines issued by scientific medical societies and the practical implementation of these guidelines by primary care physicians. In health services research this is known as the "evidence-performance gap". The aim of this narrative review is to outline the nature and the dynamics of trends in general practice/family medicine on the one hand and in the medical specialties on the other hand, and to elucidate the potential causes leading to the evidence performance gaps observed. PMID- 26558925 TI - Genetic neurological channelopathies: molecular genetics and clinical phenotypes. AB - Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID- 26558932 TI - [Circadian rhythms and chronic diseases]. AB - Everything in nature and life is occurring in a rhythmic manner. The major "Zeitgeber" is the change of light and dark during a 24 h day. This circadian rhythm is besides others reflected in circadian rhythms of behaviors or different biochemical parameters. A disruption of the circadian rhythm has a high pathophysiological potential. In this article a few basic issues about the role of circadian rhythms and the pathophysiological importance of desynchronisation are reviewed. PMID- 26558931 TI - [Is the presence of an asymptomatic inguinal hernia enough to justify repair?]. AB - The risk of strangulation in case of a inguinal hernia is low. Patients with a symptomatic inguinal hernia should undergo an operation. Morbidity and mortality in inguinal hernia surgery are very rare. There is also non-conservative treatment of inguinal hernias. Trusses should no longer be recommended. Watchful waiting is an option for men with minimally symptomatic or asymptomatic inguinal hernias. But patients must be informed that there is a high risk of becoming symptomatic. PMID- 26558933 TI - [From "psychopathy" to "personality disorder"--conceptual history of a problematic field within psychiatry]. AB - The issue of personality disorders addresses fundamental questions of psychiatry: Is there a clear boundary between normal behaviour and the state of mental illness? Which criteria are defining this boundary? Is a personality disorder really a mental illness or "just" a special variation of an individual lifestyle? This paper reviews the development of the terms psychopathy/personality disorder from the early 19th century to the present-day diagnostic manuals ICD-10 and DSM 5. This debate spreads out-as it does with regard to any other mental disorder between psychopathological, neurobiological and social sciences approaches. It is of high practical relevance to realize that nowadays effective therapeutic options for patients with personality disorders are available. Therefore, the therapeutic nihilism of earlier times is no longer justified. PMID- 26558934 TI - [Work and epilepsy--facts and phantasies]. AB - Epilepsies can affect ability to work in a certain workplace and reintegration capacity not only due the seizures, but also due to possible accompanying neurological, neuropsychological and psychiatric symptoms. Epileptic seizures can lead to injuries of the patient himself and of other persons. Assessment of this aspect in a certain workplace requires not only a detailed knowledge of the nature of this job, but also of the semiology and frequency of seizures must be considered. Both attacks and concomitant symptoms (e.g. memory impairment, depression, etc.) have to be assessed with regard to prognosis and treatment status. As part of the patient's duty to cooperate with the social insurance system it is expected that he is concerned about the regular intake of antiepileptic pharmacotherapy, possibly also of psychiatric medications. Epilepsy surgery is, however, not regarded as a reasonable treatment. PMID- 26558935 TI - [Type 2 diabetes: Cardiovascular long-term safety of sitagliptin demonstrated]. PMID- 26558936 TI - [High-dose vitamin D - No benefit for postmenopausal women]. PMID- 26558937 TI - [CME - Dermatology 9. Chronic vaginal pruritus for 2 years]. PMID- 26558940 TI - Highly parallel acoustic assembly of microparticles into well-ordered colloidal crystallites. AB - The precise arrangement of microscopic objects is critical to the development of functional materials and ornately patterned surfaces. Here, we present an acoustics-based method for the rapid arrangement of microscopic particles into organized and programmable architectures, which are periodically spaced within a square assembly chamber. This macroscale device employs two-dimensional bulk acoustic standing waves to propel particles along the base of the chamber toward pressure nodes or antinodes, depending on the acoustic contrast factor of the particle, and is capable of simultaneously creating thousands of size-limited, isotropic and anisotropic assemblies within minutes. We pair experiments with Brownian dynamics simulations to model the migration kinetics and assembly patterns of spherical microparticles. We use these insights to predict and subsequently validate the onset of buckling of the assemblies into three dimensional clusters by experiments upon increasing the acoustic pressure amplitude and the particle concentration. The simulations are also used to inform our experiments for the assembly of non-spherical particles, which are then recovered via fluid evaporation and directly inspected by electron microscopy. This method for assembly of particles offers several notable advantages over other approaches (e.g., magnetics, electrokinetics and optical tweezing) including simplicity, speed and scalability and can also be used in concert with other such approaches for enhancing the types of assemblies achievable. PMID- 26558941 TI - Safety and efficacy of targeted agents monotherapy in advanced NSCLC. AB - The emergence of targetted therapy has revolutionised the treatment of advanced NSCLC. Increasing numbers of driver genes and related targetted agents have supplied more powerful weapons for conquering NSCLC. Depending on whether there are clear targets and therapeutic effects, we can now rank targetted agents into three categories: agents with explicit targets and pure effects, agents with theoretical targets but with no effective biomarkers, agents with vague targets and lower effects. The latest clinical data on the safety and efficacy of monotherapy with three kinds of agents will be reviewed respectively in this article. PMID- 26558942 TI - Long Non-Coding RNA Urothelial Carcinoma Associated 1 (UCA1): Insight into Its Role in Human Diseases. AB - Long non-coding RNA (lncRNA) is a type of DNA transcript that is longer than 200 nucleotides (nt). They do not encode proteins, but they control gene expression on various levels. Long non-coding RNA metastasis-associated urothelial carcinoma associated 1 (UCA1) was confirmed to play an important role in the occurrence and development of many tumor and non-tumor diseases. UCA1 mainly interacts with proteins in the nucleus, regulating gene expression in transcription and post transcription. UCA1 is highly expressed in tumor tissue, and therefore can be related to clinical parameters. It may regulate tumor cell proliferation, invasion, apoptosis, and migration, so UCA1 can be applied in clinical prognosis and targeted therapy. This review mainly elaborates the roles of UCA1 in tumor diseases of the respiratory, digestive, reproductive, and urinary systems; and in non-tumor diseases. PMID- 26558943 TI - AKT as Locus of Cancer Positive Loops Conversion and Chemotherapy. AB - A cancer positive-feedback loops conversion is the phenomenon and principal mechanism for AKT locus chemotherapy. Such chemotherapy is the approach to target cancer robustness and complexity through the AKT signaling locus. The hypoxic cancer microenvironment generates a powerful signaling interactome with positive feedback loops that generates cancer robustness through the AKT locus. This complexity and robustness can be successfully halted in leukemia, lymphoma, myeloma, plasmocytoma, sarcoma, and carcinoma by converting cancer positive feedback loops into negative-feedback loops, achieved through the AKT dephosphorylation by redox balancing change. The hyperphosphorylated AKT locus is down-regulated completely to AKT dephosphorylation by redox balancing change, causing conversion of positive-feedback loops and the disappearance of malignant robustness as a direct effect of AKT locus chemotherapy. PMID- 26558944 TI - Dual Protective and Cytotoxic Benefits of Mesenchymal Stem Cell Therapy in Combination with Chemotherapy/Radiotherapy for Cancer Patients. AB - Cancer is a major health problem in the world, and scientists seek innovative treatment strategies with higher efficacy and lower toxicity than the existing therapeutic agents. In this way, stem cell researchers try to reveal new pathways that will eventually benefit patients. Stem cell research has proven that mesenchymal stem cells (MSCs) possess anticancer activities, and their protein rich secretome showed similar effects. MSCs also secrete cytokines that play an active role in healing and regeneration processes. Because of their known plasticity, MSCs display a variety of characteristics and functions in different environments, depending on their interactions with various cell types and tissues. Therefore, we hypothesize that MSC therapy in combination with anticancer medicines can potentiate cytotoxic effects on cancer cells. In addition, because of their regenerative capacity, MSCs can protect normal tissues from adverse cytotoxic drug reactions. They may also help rescue injured tissues from these toxic damages or systemic pathological events that occur during cancer treatment. MSC therapy may double the beneficial effects on cancer and normal cells. As our knowledge of systems biology and biotechnological methodology is progressing, this idea can move forward as a treatment option. PMID- 26558945 TI - Genes Associated with Human Cancers: Their Expressions, Features, Functions, and Significance. AB - Various types of cancer continue to be subjects of intense research because of the impact of these diseases and their socioeconomic implications. Also, the complexity involved in the pathogenesis, nature of the triggers, and the progression of cancers is intriguing. An important aspect of cancers is the genetics involved, and studies involving cancer genes contributed immensely in not only understanding cancers better, but also for obtaining useful markers and therapy targets. We review the salient features, functions, and changes in gene expression for 103 carcinoma genes, 20 sarcoma genes, and 36 lymphoma genes. Apart from the three major levels of cancer type, we discuss the implications of altered gene expression at the tissue level as well. The possible uses of these gene functions and expression changes for diagnostic, prognostic, and therapeutic applications are presented. Also, the 159 genes are assessed for their involvement in more than a single cancer and tissue type. Only the p53 gene is commonly implicated in carcinomas, sarcoma and lymphomas. The CHEK2 and ERBB2 (HER2) genes are commonly found to be associated with carcinomas and sarcomas, whereas the MDM2, MSH2, and MSH6 genes are commonly implicated among carcinomas and lymphomas. PMID- 26558946 TI - Jacques Monod and Chance and Necessity. AB - Charles Darwin proposed the theory that evolution of live organisms is based on random variation and natural selection. Jacques Monod, in his classic book Chance and Necessity, published 45 years ago, presented his thesis that the biosphere does not contain a predictable class of objects or events, but constitutes a particular occurrence, compatible indeed with the first principles but not deducible from those principles. The biosphere is therefore essentially unpredictable. In his book, Monod expounded at length on the conflict between science and religion. He saw religion as a collection of primitive myths that had been blown to shreds by science. At every turn, Monod emphasized the role of chance in human existence, an idea that is antithetical to essentially every religious doctrine that places humans as some inevitable intention of a Creator. PMID- 26558947 TI - Immunopathogenesis of Colitis-Associated Cancer in an Animal Model. AB - Chronic inflammation, such as that seen in patients with inflammatory bowel disease (IBD), greatly increases the risk of developing colon cancer. Growing evidence supports a role for T cell-mediated immune response and release of various cytokines in the pathogenesis of colitis-associated cancer (CAC). In fact, CD4+ effector T cells promote chronic inflammation associated with IBD through release of proinflammatory cytokines, which leads to initiation and progression of colon cancer. Furthermore, CD8+ T cells reduce tumor growth through cancer immunosurveillance, which can also contribute to intestinal inflammation and thereby might promote tumor growth. In contrast, regulatory T cells (Tregs) release the immunosuppressive cytokines IL-10, TGF-beta and thus have protective effects in CAC. In addition, dendritic cells (DCs) are important components of antitumor immunity. Recently, a novel mouse model that was associated with repeated inflammation was established for investigating the immunopathogenesis of CAC. This review discusses the role of T cell-mediated immune response, and DCs and involved cytokines in the immunopathogenesis of CAC in an animal model, which may also provide future therapeutic targets in CAC. PMID- 26558948 TI - The Key Role of Mitochondrial Apoptotic Pathway in the Cytotoxic Effect of Mushroom Extracts on Cancer Cells. AB - Mushroom extracts have been extensively studied for their medicinal effects. They can stimulate immune responses and thus have been explored in cancer treatment. Recently, it has also been shown that some mushroom extracts can produce direct cytotoxic effect on cancer cells. In this review, we summarize the cytotoxic effect of mushroom extracts in cancer treatment revealed by both in vitro and in vivo studies. We also summarize the current understanding of the mechanisms associated with such an effect with an emphasis on the mitochondrial apoptotic pathway. The recent finding that mushroom extracts have direct cytotoxic effects supplements their known immune stimulating effects. Thus, novel anticancer agents based on new findings from mushroom extracts may soon be added to the present pool of anticancer drugs. Specifically, we propose that nanodelivery of the bioactive compounds of mushroom extracts to mitochondria will further increase their potential treatment efficacy. PMID- 26558949 TI - Roles of Protein N-Myristoylation and Translational Medicine Applications. AB - Protein N-myristoylation is a ubiquitous cotranslational and posttranslational modification catalyzed by myristoyl CoA:protein N-myristoyltransferase (NMT), which attaches myristate, a rare 14-carbon saturated fatty acid, to an N-terminal glycine of some eukaryotic and virus proteins. This protein modification triggers dynamic protein-protein and protein-membrane interactions implicated in diverse physiological processes. This review summarizes the NMT catalytic mechanism and demyristoylation. Of special interest are the primary roles of N-myristoylated protein in signaling, protein targeting, tumorigenesis, apoptosis, virus assembly, and morphology change, as well as the regulation of N-myristoylation and NMT inhibitors. PMID- 26558950 TI - Epithelial Mesenchymal Transition and Vascular Mimicry in Breast Cancer Stem Cells. AB - Vasculogenic mimicry (VM), a newly defined pattern of tumor microvascularization differs from angiogenesis and vasculogenesis in its noninvolvement of endothelial cells, by which highly aggressive tumor cells can form vessel-like structures themselves, because of their high plasticity. The presence of VM has been shown to be strongly associated with a poor prognosis in several types of cancer, but biological features of tumor cells that form VM remains unknown. Human breast cancer, characterized by a group of highly heterogeneous lesions, is the most common cancer in women and one of the leading causes of cancer-related deaths worldwide. The epithelialmesenchymal transition (EMT) state in breast cancer has been associated with cancer stem cell (CSC) properties, self-renewal capabilities, resistance to conventional therapies, and a tendency for posttreatment recurrence. With increasing knowledge about cancer stem cell phenotypes and functions, they are implicated in VM formation. Studies also indicate that EMT is relevant to the acquisition and maintenance of stem cell like characteristics and is involved in VM. This review discusses the correlation between CSCs, EMT, and VM formation with a focus on breast cancer. Also, the signalling molecules and pathways involved in VM and some recently defined direct VM targeting strategies in breast cancer are reviewed here. PMID- 26558951 TI - Development of an algorithm for the management of cervical lymphadenopathy in children: consensus of the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases and the Italian Society of Pediatric Otorhinolaryngology. AB - Cervical lymphadenopathy is a common disorder in children due to a wide spectrum of disorders. On the basis of a complete history and physical examination, paediatricians have to select, among the vast majority of children with a benign self-limiting condition, those at risk for other, more complex, diseases requiring laboratory tests, imaging and, finally, tissue sampling. At the same time, they should avoid expensive and invasive examinations when unnecessary. The Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases, the Italian Society of Pediatric Otorhinolaryngology, and other Scientific Societies, issued a National Consensus document, based on the most recent literature findings, including an algorithm for the management of cervical lymphadenopathy in children. METHODS: The Consensus Conference method was used, following the Italian National Plan Guidelines. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through March 21, 2014. RESULTS: Basing on literature results, an algorithm was developed, including several possible clinical scenarios. Situations requiring a watchful waiting strategy, those requiring an empiric antibiotic therapy, and those necessitating a prompt diagnostic workup, considering the risk for a severe underling disease, have been identified. CONCLUSION: The present algorithm is a practice tool for the management of pediatric cervical lymphadenopathy in the hospital and the ambulatory settings. A multidisciplinary approach is paramount. Further studies are required for its validation in the clinical field. PMID- 26558952 TI - Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles. AB - In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles. PMID- 26558953 TI - Immunotherapy (oral and sublingual) for food allergy to fruits. AB - BACKGROUND: Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). OBJECTIVES: To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. MAIN RESULTS: We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the results. A study comparing SLIT with placebo for allergy to peach did not detect a significant difference between the number of patients desensitised at six months following a double-blind placebo controlled food challenge (RR 1.16, 95% confidence interval (CI) 0.49 to 2.74). The second study, comparing OIT versus no treatment for apple allergy, found an effect on desensitisation in favour of the intervention using an oral provocation test at eight months, but results were imprecise (RR 17.50, 95% CI 1.13 to 270.19). Neither study reported data on evidence of immunologic tolerance. In both studies, the incidence of mild and moderate adverse events was higher in the intervention groups than in the controls. In the study comparing SLIT with placebo, patients in the intervention group experienced significantly more local adverse reactions than participants in the control group (RR 3.21, 95% CI 1.51 to 6.82), though there was not a significant difference in the number of participants experiencing systemic adverse reactions (RR 0.81, 95% CI 0.22 to 3.02). In the study of OIT, two of the 25 participants in the intervention group reported relevant side effects, whereas no participants in the control group reported relevant side effects. AUTHORS' CONCLUSIONS: There is insufficient evidence for using OIT or SLIT to treat allergy to fruit, specifically related to peach and apple. Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT. However, these reactions could be treated successfully with medications. PMID- 26558954 TI - Impairments of Lower Extremity Muscle Strength and Balance in Childhood Cancer Patients and Survivors: A Systematic Review. AB - This review aims to summarize the evidence for impairments of muscle strength and balance during and after treatment for childhood cancer. Thirty-two articles, identified in scientific databases by means of a structured search for investigations of muscle strength and balance in pediatric cancer patients and survivors, are evaluated. A summary of results is given with respect to matching reporting items to provide a qualitative analysis of the evidence. The majority of the studies reached a level 3 rating according to Oxford Centre for Evidence Based Medicine (OCEBM) 2011 levels of evidence. Muscle strength and balance seem to be impaired in varying degrees depending on the diagnosis, treatment received, and time elapsed between treatment and evaluation. Drawing specific conclusions from the identified studies is difficult because of heterogeneous study samples and methods of research. Individual targeted exercise therapy programs during treatment and follow-up of childhood cancer could help to prevent and further diminish impairments of muscle strength and balance function among childhood cancer patients and survivors. PMID- 26558955 TI - Review of conventional and novel food processing methods on food allergens. AB - With the turn of this century, novel food processing techniques have become commercially very important because of their profound advantages over the traditional methods. These novel processing methods tend to preserve the characteristic properties of food including their organoleptic and nutritional qualities better when compared with the conventional food processing methods. During the same period of time, there is a clear rise in the populations suffering from food allergies, especially infants and children. Though, this fact is widely attributed to the changing livelihood of population in both developed and developing nations and to the introduction of new food habits with advent of novel foods and new processing techniques, their complete role is still uncertain. Under the circumstance, it is very important to understand the structural changes in the protein as food is processed to comprehend whether the specific processing technique (conventional and novel) is increasing or mitigating the allergenicity. Various modern means are now being employed to understand the conformational changes in the protein which can affect the allergenicity. In this review, the processing effects on protein structure and allergenicity are discussed along with the insinuations of recent studies and techniques for establishing a platform to investigate future pathway to reduce or eliminate allergenicity in the population. PMID- 26558956 TI - Diagnosis of a public policy: an introduction to user fee exemptions for healthcare in the Sahel. AB - During the last ten years, Burkina Faso, Mali and Niger have opted for selective user fee exemption policies, while remaining within the general framework of cost recovery. But they have each developed their own particular institutional mechanisms, different from those of their neighbour. This was the topic of a comparative research program combining both quantitative and qualitative surveys over a four-year period. This special issue presents papers setting exemption policies in the wider context of public policy and the day-to-day functioning of health systems (part 1); presenting overarching case studies (part 2); and reflecting on our methodological approach (part 3). PMID- 26558957 TI - Analysis of posttraumatic stress disorder in children with road traffic injury in Wenzhou, China. AB - OBJECTIVE: Road traffic accidents are the leading health threat to children and cause significant long-term mental health problems. This study aimed to characterize posttraumatic stress disorder (PTSD) in children suffering from road traffic injuries (RTIs) in Wenzhou, China. METHODS: We conducted a retrospective study of 537 children (aged 1 to 13 years old) with RTIs. The epidemiological features, PTSD incidence, clinical manifestation, and risk factors were analyzed based on a customized PTSD risk factor questionnaire. The outcome factors were also evaluated by means of the logistic regression method. RESULTS: The PTSD incidence was 24.77% in children with RTIs. The incidence of PTSD was related to the personality, family environment, and family care of the children. It was found that early psychological intervention and reasonable family care from the family might promote physical and mental welfare as well as contribute to the development of more effective treatments to prevent PTSD. CONCLUSION: For susceptible children, in addition to dealing with the somatic injury, psychological intervention and family care should be carried out as early as possible. PMID- 26558958 TI - Utility of Postoperative Antibiotics After Percutaneous Pinning of Pediatric Supracondylar Humerus Fractures. AB - BACKGROUND: Pediatric supracondylar humerus fractures are common injuries that are often treated surgically with closed reduction and percutaneous pinning. Although surgical-site infections are rare, postoperative antibiotics are frequently administered without evidence or guidelines for their use. With the increasing prevalence of antibiotic-resistant organisms and heightened focus on health care costs, appropriate and evidence-based use of antibiotics is needed. We hypothesized that postoperative antibiotic administration would not decrease the rate of surgical-site infection. METHODS: A billing query identified 951 patients with operatively treated supracondylar humerus fractures at our institution over a 15-year period. Records were reviewed for demographic data, perioperative antibiotic use, and the presence of surgical-site infection. Exclusion criteria were open fractures, open reduction, pathologic fractures, metabolic bone disease, the presence of other injuries that required operative treatment, and follow-up <2 weeks after pin removal. chi and Fisher exact test were used to compare antibiotic use to the incidence of surgical-site infection. RESULTS: Six hundred eighteen patients met our inclusion criteria. Two hundred thirty-eight patients (38.5%) received postoperative antibiotics. Eleven surgical site infections were identified for an overall rate of 1.8%. The use of postoperative antibiotics was not associated with a lower rate of surgical-site infection (P=0.883). Patients with a type III fracture (P<0.001), diminished preoperative vascular (P=0.001) and neurological status (P=0.019), and postoperative hospital admission (P<0.001) were significantly more likely to receive postoperative antibiotics. CONCLUSIONS: Administration of postoperative antibiotics after closed reduction and percutaneous pinning of pediatric supracondylar humerus fractures does not decrease the rate of surgical-site infection. LEVEL OF EVIDENCE: Level III-therapeutic. PMID- 26558959 TI - Which Pediatric Orthopaedic Procedures Have the Greatest Risk of Adverse Outcomes? AB - BACKGROUND: Quality improvement in orthopaedic surgery has received increasing attention; however, there is insufficient information available about the perioperative safety of many common pediatric orthopaedic procedures. This study aimed to characterize the incidence of adverse events in a national pediatric patient sample to understand the risk profiles of common pediatric orthopaedic procedures, and to identify patients and operations that are associated with increased rates of adverse outcomes. METHODS: A retrospective cohort study was conducted using the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Pediatric database. Pediatric patients who underwent 29 different orthopaedic procedures were identified in the 2012 NSQIP Pediatric database. The occurrence of any adverse event, infection, return to the operating room, and readmission within 30 days, were reported for each procedure. Multivariate regression was then used to identify the association of patient and operative characteristics with the occurrence of each adverse outcome. RESULTS: A total of 8975 pediatric patients were identified. Supracondylar humerus fracture fixation was the most common procedure performed in this sample (2274 patients or 25.57% of all procedures), followed by posterior spinal fusion (1894 patients or 21.10% of all procedures). Adverse events occurred in 352 patients (3.92% of all patients). Four deaths were noted (0.04% of all patients), which only occurred in patients with nonidiopathic scoliosis undergoing spinal fusion. Infections occurred in 143 patients (1.59%), and 197 patients (2.19%) were readmitted within 30 days. Multiple patient characteristics and procedures were found to be associated with each adverse outcome studied. CONCLUSIONS: Spinal fusion, multiaxial external fixation, and fasciotomy were procedures associated with increased rates of adverse outcomes within 30 days. Patients with obesity, ASA class >=3, and impaired cognitive status also had increased rates of adverse outcomes. The results from this study of a large, national sample of pediatric orthopaedic patients are important for benchmarking and highlight areas for quality improvement. LEVEL OF EVIDENCE: Level III Prognostic. PMID- 26558960 TI - Solvent interaction analysis as a proteomic approach to structure-based biomarker discovery and clinical diagnostics. AB - Proteins have several measurable features in biological fluids that may change under pathological conditions. The current disease biomarker discovery is mostly based on protein concentration in the sample as the measurable feature. Changes in protein structures, such as post-translational modifications and in protein partner interactions are known to accompany pathological processes. Changes in glycosylation profiles are well-established for many plasma proteins in various types of cancer and other diseases. The solvent interaction analysis method is based on protein partitioning in aqueous two-phase systems and is highly sensitive to changes in protein structure and protein-protein- and protein partner interactions while independent of the protein concentration in the biological sample. It provides quantitative index: partition coefficient representing changes in protein structure and interactions with partners. The fundamentals of the method are presented with multiple examples of applications of the method to discover and monitor structural protein biomarkers as disease specific diagnostic indicators. PMID- 26558961 TI - Progress takes a lot of pushing. AB - Despite the pace of healthcare progress, it seems that some things never change. PMID- 26558963 TI - Website will help practitioners diagnose illnesses in children. AB - NURSES AND child health practitioners will soon be offered a major online resource to spot symptoms of childhood illnesses and manage critical care situations. PMID- 26558964 TI - Campaign calls for statutory first aid training in schools. AB - NURSES ARE being urged to back a campaign to make first aid compulsory in all state-funded secondary schools. PMID- 26558965 TI - More distinct nurse roles needed for looked after children. AB - THE RCN has called for all clinical commissioning groups (CCGs) to employ full time designated and named nurses for looked after children to improve health outcomes. PMID- 26558967 TI - New 'passport' will improve mental health care journey. AB - A PASSPORT-STYLE brief of key facts that children and young people using mental health services can use to help them avoid repeating their history and preferences has been launched by NHS England. PMID- 26558968 TI - Staff shortage puts neonatal services under strain. AB - A 'SEVERE shortage' of neonatal nurses and doctors in England is leaving services 'over-stretched and under incredible pressure', a survey suggests. PMID- 26558969 TI - Mixed views on plans for the profession. AB - ENGLAND'S CHIEF nursing officer Jane Cummings and her team are busy drawing up the first draft of a new nursing and midwifery strategy, to be presented to about 500 senior nurses attending the chief nurse's annual two-day summit in Birmingham on December 1-2. PMID- 26558974 TI - Research essentials. How to critique quantitative research. AB - QUANTITATIVE RESEARCH is a systematic approach to investigating numerical data and involves measuring or counting attributes, that is quantities. Through a process of transforming information that is collected or observed, the researcher can often describes a situation or event, answering the 'what' and 'how many' questions about a situation ( Parahoo 2014 ). PMID- 26558975 TI - Research and commentary. How cultural barriers provide a challenge to health visitors. AB - BACKGROUND: Families with young children, including those from minority ethnic communities, receive support and advice from health visitors. While the need for cultural sensitivity is being increasingly recognised, the factors that contribute to this sensitivity are often poorly understood. This study took place in an urban area of Scotland and involved families from the two largest minority ethnic groups in the country: Pakistani and Chinese. The experiences that mothers had of the health visiting service and with health visitors were explored, as well as experiences that health visitors had with Pakistani and Chinese clients. PMID- 26558976 TI - Establish a rapport that allows clear communication. AB - The population in the UK is now more diverse than ever before. It is vital that healthcare services are equally sensitive to the beliefs of those who come from minority ethnic groups. The primary theme gathered from the study was the ability of families to balance traditional and Western values into their lifestyles. PMID- 26558981 TI - Tales from the city. AB - THE PAST 10 months have been eventful to say the least. I went straight from finishing my nursing internship to volunteering in a hospice for abandoned children in China. On my return I moved from Ireland to London and started my first job as a staff nurse in the paediatric intensive care unit (PICU) at Great Ormond Street Hospital. PMID- 26558982 TI - How seminars for parents can improve children's continence management. AB - Staff at a children's urology department, in response to a growing caseload and reports of a sense of isolation among children, young people and their carers, agreed there was a need to develop innovative new strategies to provide a quality service that could be delivered within existing financial constraints. The aim was to encourage service users while showing them they were not alone and without breaching confidentiality. Paediatric urology seminars for parents were developed as a result and they have proven to be effective, including in areas that were not at first anticipated, such as parents being able to appreciate from a non judgmental approach that their children are neither naughty nor lazy. PMID- 26558983 TI - Suspect, detect and protect: lessons from a lipohypertrophy workshop for children's nurses. AB - This article describes a recent training workshop to educate children's nurses on injection technique best practice for diabetes, in particular, lipohypertrophy. The workshop was organised by the Forum for Injection Technique UK, the University of York, Leeds Children's Diabetes Team and Becton Dickinson Signature Solutions, and attended by delegates from Leeds Children's Hospital and the Children and Young Peoples Diabetes Network for Yorkshire and the Humber. The article discusses the causes of lipohypertrophy and the effect it can have on patient's glycaemic levels. There is an emphasis on the importance of regularly inspecting children and young people with diabetes for lipohypertrophy - a common complication of diabetes injection - and promotes the motto 'suspect, detect and protect'. The article also provides practical information for children's nurses on how to examine for lipohypertrophic lesions and guidance on how they can be prevented by adhering to correct injection technique. PMID- 26558984 TI - Management of vitamin D deficiency in childhood and adolescence. AB - There are some children and young people who will need specialist management for vitamin D deficiency in paediatric endocrine services. However, health problems caused by vitamin D deficiency are generally preventable, hence the National Institute for Health and Care Excellence recommendations for the provision of NHS Healthy Start vitamins to be available to all pregnant and breastfeeding women and children under five years of age. All health professionals, not just specialist services, need to be confident in their knowledge and understanding of the importance of vitamin D in normal growth and development to enable early identification of children and young people at risk who are in need of early intervention and education. PMID- 26558985 TI - Youthful outlook. AB - Why did you become a children's nurse? My undergraduate degree was in sports therapy, a great profession and still a large passion of mine. However it was during my placements as a sports therapist that I recognised that helping people, talking to them and making them feel better was the part of the job I enjoyed the most, particularly with young athletes. I applied to do a postgraduate in children's nursing and here I am now. PMID- 26558986 TI - A chick embryo cryoinjury model for the study of embryonic organ development and repair. AB - Tissue ablation is a classic experimental approach to study early embryo patterning. However, ablation methods are less frequently used to assess the reparative or regenerative properties of embryonic tissues during organogenesis. Surgical procedures based on the removal of a significant amount of tissue during organ formation very much depend on the skills of the researcher, are difficult to reproduce, and often result in extensive tissue disruption leading to embryonic death. In this paper, we present a new protocol to generate discrete, locally-restricted and highly reproducible wounds in the developing chick embryo using a liquid N2-cooled metallic probe. This in ovo procedure allows for the study of organ-specific tissue responses to damage, such as compensatory cell growth, cell differentiation, and reparative/regenerative mechanisms throughout the embryonic lifespan. PMID- 26558988 TI - Tricuspid leaflet resection in an open beating heart for the creation of a canine tricuspid regurgitation model. AB - OBJECTIVES: Outcomes of tricuspid valve replacement are poor, partly due to right heart remodelling. The research on its underlying mechanisms is hampered by a lack of animal models of tricuspid regurgitation (TR). Our objective was to create a reproducible and clinically compatible TR animal model to study right heart remodelling caused by TR. METHODS: Fourteen juvenile male Beagle dogs were divided randomly into an intervention group (n = 11) and a sham-operated control group (n = 3). The intervention group underwent thoracotomy and right atrial incision following superior and inferior vena caval occlusion. The anterior leaflet, together with the chordae, of the tricuspid valve was resected in eight dogs ('one leaflet' group), whereas both anterior and posterior leaflets, together with the chordae, were resected in three dogs ('two leaflets' group). The right atrium and chest were then closed. The control group underwent the same procedure, except leaflet resection. One dog from the 'two leaflets' group and one control dog were sacrificed and autopsy was performed at 12 months post surgery. RESULTS: All dogs survived over the 1-year observation period postoperatively. TR grade IV occurred immediately postoperatively in the 'one leaflet' group, and TR grade IV plus in the 'two leaflets' group. The overall procedure lasted 30-40 min, and the mean time of vena caval occlusion was 87 +/- 10 s. Central venous pressure increased from 6 +/- 1.2 at baseline to 13 +/- 1.7 mmHg (P < 0.01). By 12 months after TR creation, both in the 'one leaflet' group and in the 'two leaflets' group, the right atrial area, tricuspid annular diameter and right ventricular index of myocardial performance increased significantly, right ventricular fractional area change and tricuspid annular plane systolic excursion decreased significantly. Autopsy of the intervention dog revealed oedema, ascites and cirrhosis. CONCLUSIONS: Our surgical technique to create a TR animal model was reproducible with high success and survival rates. This animal model would prove suitable to investigate the mechanisms of right heart remodelling. PMID- 26558987 TI - Islet Neogenesis Associated Protein (INGAP) induces the differentiation of an adult human pancreatic ductal cell line into insulin-expressing cells through stepwise activation of key transcription factors for embryonic beta cell development. AB - Regeneration of beta-cells in diabetic patients is an important goal of diabetes research. Islet Neogenesis Associated Protein (INGAP) was discovered in the partially duct-obstructed hamster pancreas. Its bioactive fragment, pentadecapeptide 104-118 (INGAP-P), has been shown to reverse diabetes in animal models and to improve glucose homeostasis in patients with diabetes in clinical trials. Further development of INGAP as a therapy for diabetes requires identification of target cells in the pancreas and characterization of the mechanisms of action. We hypothesized that adult human pancreatic ductal cells retain morphogenetic plasticity and can be induced by INGAP to undergo endocrine differentiation. To test this hypothesis, we treated the normal human pancreatic ductal cell line (HPDE) with either INGAP-P or full-length recombinant protein (rINGAP) for short-term periods. Our data show that this single drug treatment induces both proliferation and transdifferentiation of HPDE cells, the latter being characterized by the rapid sequential activation of endocrine developmental transcription factors Pdx-1, Ngn3, NeuroD, IA-1, and MafA and subsequently the expression of insulin at both the mRNA and the protein levels. After 7 days, C peptide was detected in the supernatant of INGAP-treated cells, reflecting their ability to secrete insulin. The magnitude of differentiation was enhanced by embedding the cells in Matrigel, which led to islet-like cluster formation. The islet-like clusters cells stained positive for nuclear Pdx-1 and Glut 2 proteins, and were expressing Insulin mRNA. These new data suggest that human adult pancreatic ductal cells retain morphogenetic plasticity and demonstrate that a short exposure to INGAP triggers their differentiation into insulin-expressing cells in vitro. In the context of the urgent search for a regenerative and/or cellular therapy for diabetes, these results make INGAP a promising therapeutic candidate. PMID- 26558989 TI - NovoTTFTM-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTALTM system user study. AB - BACKGROUND: OptuneTM, previously known as the NovoTTF-100A SystemTM, generates Tumor Treating Fields (TTFields), an effective anti-mitotic therapy for glioblastoma. The system delivers intermediate frequency, alternating electric fields to the supratentorial brain. Patient therapy is personalized by configuring transducer array layout placement on the scalp to the tumor site using MRI measurements and the NovoTAL System. Transducer array layout mapping optimizes therapy by maximizing electric field intensity to the tumor site. This study evaluated physician performance in conducting transducer array layout mapping using the NovoTAL System compared with mapping performed by the Novocure in-house clinical team. METHODS: Fourteen physicians (7 neuro-oncologists, 4 medical oncologists, and 3 neurosurgeons) evaluated five blinded cases of recurrent glioblastoma and performed head size and tumor location measurements using a standard Digital Imaging and Communications in Medicine reader. Concordance with Novocure measurement and intra- and inter-rater reliability were assessed using relevant correlation coefficients. The study criterion for success was a concordance correlation coefficient (CCC) >0.80. RESULTS: CCC for each physician versus Novocure on 20 MRI measurements was 0.96 (standard deviation, SD +/- 0.03, range 0.90-1.00), indicating very high agreement between the two groups. Intra- and inter-rater reliability correlation coefficients were similarly high: 0.83 (SD +/-0.15, range 0.54-1.00) and 0.80 (SD +/-0.18, range 0.48-1.00), respectively. CONCLUSIONS: This user study demonstrated an excellent level of concordance between prescribing physicians and Novocure in-house clinical teams in performing transducer array layout planning. Intra-rater reliability was very high, indicating reproducible performance. Physicians prescribing TTFields, when trained on the NovoTAL System, can independently perform transducer array layout mapping required for the initiation and maintenance of patients on TTFields therapy. PMID- 26558990 TI - Staining histological lung sections with Sudan Black B or Sudan III for automated identification of alveolar epithelial type II cells. AB - Alveolar epithelial type II (AE2) cells produce, store and secrete pulmonary surfactant and serve as progenitor cells for the alveolar epithelium. They are thus an interesting target in wide fields of pulmonary research. Stereological methods allow their quantification based on measurements on histological sections. A proper AE2 cell quantification, however, requires a method of tissue processing that results in little tissue shrinkage during processing. It was recently shown that a primary fixation with a mixture of glutaraldehyde and formaldehyde, postfixation with osmium tetroxide and uranyl acetate and embedding in glycol methacrylate fulfills this requirement. However, a proper quantification, furthermore, requires a secure identification of the cells under the microscope. Classical approaches using routine stainings, high magnifications and systematic uniform random sampling can result in a tedious counting procedure. In this article we show that Sudan Black B and Sudan III staining in combination with the previously described "low shrinkage method" of tissue processing result in good staining of lamellar bodies of AE2 cells (their storing organelles of surfactant) and thus provide a good signal of AE2 cells, which allows their easy and secure identification even at rather low magnifications. We further show that this signal enables automated detection of AE2 cells by image analysis, which should make this method a suitable staining method for the recently developed and more efficient proportionator sampling. PMID- 26558991 TI - Immunohistochemical expression of WNT5A and MMPs in odontogenic epithelial tumors and cysts. AB - OBJECTIVE: The aim of this study was compare the expression of WNT5A and MMP2, 7 and 20, in frequent benign odontogenic tumors and odontogenic cysts, since these lesions have a different biological behavior. MATERIALS AND METHODS: Eighty-one paraffin-embedded specimens of odontogenic tumors, including ameloblastoma and keratocystic odontogenic tumor, and thirty-two odontogenic cysts were used for immunohistochemical analysis. RESULTS: The expression of WNT5A in odontogenic tumors and inflammatory cyst was higher than in developmental odontogenic cyst. There was no statistical difference (p<0.05) in the expression of WNT5A when comparing the analyzed tumors. The expression of MMP7 was lower in RC with a statistical difference when compared with all tumors and cysts. Statistical differences also occurred when comparing glandular odontogenic cyst (GOC) to keratocyst odontogenic tumor (KOT) and calcifying cystic odontogenic tumor (CCOT). MMP20 expression was higher in ameloblastoma when compared to adenomatoid odontogenic tumor (AOT), DC and GOC. The expression of MMP20 was lower in CCOT when compared to all tumors and cysts. CONCLUSIONS: The expression of WNT5A in a group of odontogenic lesions suggests the participation of a non-canonical WNT signaling pathway in the progression and maintenance of these lesions. These molecules are possibly involved in the biological differences between odontogenic tumors and cysts. Considering previous studies, WNT5A may help promote the calcification seen in AOT, CCOT and CEOT by activating MMP7. PMID- 26558992 TI - Molecular cloning, expression and characterization of 100K gene of fowl adenovirus-4 for prevention and control of hydropericardium syndrome. AB - Fowl adenovirus-4 is an infectious agent causing Hydropericardium syndrome in chickens. Adenovirus are non-enveloped virions having linear, double stranded DNA. Viral genome codes for few structural and non structural proteins. 100K is an important non-structural viral protein. Open reading frame for coding sequence of 100K protein was cloned with oligo histidine tag and expressed in Escherichia coli as a fusion protein. Nucleotide sequence of the gene revealed that 100K gene of FAdV-4 has high homology (98%) with the respective gene of FAdV-10. Recombinant 100K protein was expressed in E. coli and purified by nickel affinity chromatography. Immunization of chickens with recombinant 100K protein elicited significant serum antibody titers. However challenge protection test revealed that 100K protein conferred little protection (40%) to the immunized chicken against pathogenic viral challenge. So it was concluded that 100K gene has 2397 bp length and recombinant 100K protein has molecular weight of 95 kDa. It was also found that the recombinant protein has little capacity to affect the immune response because in-spite of having an important role in intracellular transport & folding of viral capsid proteins during viral replication, it is not exposed on the surface of the virus at any stage. PMID- 26558993 TI - Association between pulmonologists' tobacco use and their effort in promoting smoking cessation in Turkey: a cross-sectional study. AB - BACKGROUND: A strategy to reduce the number of smoking-related deaths is to encourage the involvement of health-care professionals in tobacco-use prevention activities and cessation counseling. Previous studies have shown that physicians' smoking status affects their efforts to provide smoking cessation counseling. This study investigates the association between pulmonologists' tobacco use and their efforts in promoting smoking cessation during their routine clinical practices in Turkey. METHODS: This cross-sectional study was performed among active members of the Turkish Thoracic Society (TTS) between June 2010 and February 2011 using an Internet-based self-administered questionnaire. Participants gave their written informed consent. The survey included questions about responders' sociodemographics, smoking status, and their routine clinical practice for smoking cessation counseling using the basic 5A's (Ask, Advise, Assess, Assist, and Arrange) of smoking cessation counseling. According to the total score for the 5A's protocol, smoking cessation counseling was dichotomized into low- and high-effort groups in promoting smoking cessation. Pearson's chi square test and t-test were used to compare groups and logistic regression models for the research question, which was approved by the TTS Scientific Ethical Committee. RESULTS: The response rate was 41 % (N = 699/1701); 9.9 % were current smokers, and 72.7 % indicated that they provided high effort in promoting smoking cessation. A univariate analysis showed that noncurrent smokers were more likely to make a high effort than current smokers (odds ratio [OR], 1.82; 95 % confidence interval [CI]: 1.09-3.05; P = 0.02). However, there was no association between tobacco use (current smoking) and making high effort in promoting smoking cessation after controlling for the two confounders, sex and practicing in smoking cessation outpatient clinic (OR, 1.47; 95 % CI: 0.86-2.50; P = 0.1). CONCLUSIONS: Despite low response rate in our study and suspicions of underreporting, the smoking rate among the pulmonologists in our study was high. Non-current smokers were more likely to provide high effort in promoting smoking cessation compared to current smokers in univariate analysis. However, after controlling for the two confounders, sex and practising in SCOC, there was no association between tobacco use and providing high effort in promoting smoking cessation. Thus, improving medical school education, specialty training and post graduate training on smoking cessation counseling may positively affect physician' effort in promoting smoking cessation. PMID- 26558995 TI - Effect of acoustic field parameters on arc acoustic binding during ultrasonic wave-assisted arc welding. AB - As a newly developed arc welding method, power ultrasound has been successfully introduced into arc and weld pool during ultrasonic wave-assisted arc welding process. The advanced process for molten metals can be realized by utilizing additional ultrasonic field. Under the action of the acoustic wave, the plasma arc as weld heat source is regulated and its characteristics make an obvious change. Compared with the conventional arc, the ultrasonic wave-assisted arc plasma is bound significantly and becomes brighter. To reveal the dependence of the acoustic binding force on acoustic field parameters, a two-dimensional acoustic field model for ultrasonic wave-assisted arc welding device is established. The influences of the radiator height, the central pore radius, the radiator radius, and curvature radius or depth of concave radiator surface are discussed using the boundary element method. Then the authors analyze the resonant mode by this relationship curve between acoustic radiation power and radiator height. Furthermore, the best acoustic binding ability is obtained by optimizing the geometric parameters of acoustic radiator. In addition, three concave radiator surfaces including spherical cap surface, paraboloid of revolution, and rotating single curved surface are investigated systematically. Finally, both the calculation and experiment suggest that, to obtain the best acoustic binding ability, the ultrasonic wave-assisted arc welding setup should be operated under the first resonant mode using a radiator with a spherical cap surface, a small central pore, a large section radius and an appropriate curvature radius. PMID- 26558994 TI - Comparison of single CT scan assessment of bone mineral density, vascular calcification and fat mass with standard clinical measurements in renal transplant subjects: the ABC HeART study. AB - BACKGROUND: Despite limitations of routine methods, Clinical Practice Guidelines support the assessment of bone mineral density (BMD) and vascular calcification in renal transplant recipients. Changes in fat mass also occur post transplantation, although they are traditionally difficult to measure accurately. We report the feasibility, convenience and accuracy of measuring the above 3 parameters using a novel CT protocol. METHODS: We conducted a cross-sectional study of 64 first renal allograft recipients (eGFR > 30 ml/min/1.73 m(2)). Quantitative CT (QCT) BMD analysis was conducted using CT lumbar spine (GE Medical Systems Lightspeed VCT & Mindways QCT Pro Bone Mineral Densitometry System Version 4.2.3) to calculate spinal volumetric BMD and compared with standard DXA calculated areal BMD at the spine, hip and distal forearm. Abdominal aortic calcification was assessed by semi-quantitative Aortic Calcification Index (ACI) method and compared with lateral lumbar x-ray Kappuila score and pulse wave velocity (PWV). Visceral and subcutaneous adipose tissue volume (Osirix 16 Ver 3.7.1) was compared with BMI. RESULTS: Participants were 61 % male, had a mean age of 47 years, median ESKD duration of 5.4 years and a mean eGFR of 54 ml/min. iDXA median T-score at proximal femur was -1.2 and at lumbar spine was -0.2. Median QCT Trabecular T-score at lumbar spine was -1.2. The percent of subjects with a T-score of < 2.5 by site and method was DXA Proximal Femur: 7 %, DXA distal radius: 17 %, DXA spine: 9 %, QCT (American College of Radiology cutoffs): 9 %. CT derived ACI correlated with PWV (r = 0.29, p = 0.02), pulse wave pressure (r = 0.51, p < 0.001), QCT Trabecular (-0.31, p = 0.01) and cortical volumetric BMD and history of cardiovascular events (Mann-Whitney U, p = 0.02). Both visceral and subcutaneous adipose tissue correlated with BMI (r = 0.63 & 0.64, p < 0.001). CONCLUSIONS: Single CT scan triple assessment of BMD, vascular calcification and body composition is an efficient, accurate and convenient method of risk factor monitoring post renal transplantation. PMID- 26558996 TI - Effect of ultrasonic pretreatment on kinetics of gelatin hydrolysis by collagenase and its mechanism. AB - Gelatin is a mixture of soluble proteins prepared by partial hydrolysis of native collagen. Gelatin can be enzymatically hydrolyzed to produce bioactive hydrolysates. However, the preparation of gelatin peptide with expected activity is usually a time-consuming process. The production efficiency of gelatin hydrolysates needs to be improved. In present work, effect of ultrasonic pretreatment on kinetic parameters of gelatin hydrolysis by collagenase was investigated based on an established kinetic model. With ultrasonic pretreatment, reaction rate constant and enzyme inactivation constant were increased by 27.5% and 27.8%, respectively. Meanwhile, hydrolysis activation energy and enzyme inactivation energy were reduced by 36.3% and 43.0%, respectively. In order to explore its possible mechanism, influence of sonication on structural properties of gelatin was determined using atomic force microscopy, particle size analyzer, fluorescence spectroscopy, protein solubility test and Fourier transform infrared spectroscopy. Moreover, hydrogen peroxide was used as a positive control for potential sonochemical effect. It was found that reduction of gelatin particle size was mainly caused by physical effect of ultrasound. Increased solubility and variation in beta-sheet and random coil elements of gelatin were due to sonochemical effect. Both physical and chemical effects of sonication contributed to the change in alpha-helix and beta-turn structures. The current results suggest that ultrasound can be potentially applied to stimulate the production efficiency of gelatin peptides, mainly due to its effects on modification of protein structures. PMID- 26558997 TI - Sonochemical water splitting in the presence of powdered metal oxides. AB - Kinetics of hydrogen formation was explored as a new chemical dosimeter allowing probing the sonochemical activity of argon-saturated water in the presence of micro- and nano-sized metal oxide particles exhibiting catalytic properties (ThO2, ZrO2, and TiO2). It was shown that the conventional sonochemical dosimeter based on H2O2 formation is hardly applicable in such systems due to catalytic degradation of H2O2 at oxide surface. The study of H2 generation revealed that at low-frequency ultrasound (20 kHz) the sonochemical water splitting is greatly improved for all studied metal oxides. The highest efficiency is observed for relatively large micrometric particles of ThO2 which is assigned to ultrasonically-driven particle fragmentation accompanied by mechanochemical water molecule splitting. The nanosized metal oxides do not exhibit particle size reduction under ultrasonic treatment but nevertheless yield higher quantities of H2. The enhancement of sonochemical water splitting in this case is most probably resulting from better bubble nucleation in heterogeneous systems. At high frequency ultrasound (362 kHz), the effect of metal oxide particles results in a combination of nucleation and ultrasound attenuation. In contrast to 20 kHz, micrometric particles slowdown the sonolysis of water at 362 kHz due to stronger attenuation of ultrasonic waves while smaller particles show a relatively weak and various directional effects. PMID- 26558998 TI - The COMET initiative database: progress and activities update (2014). AB - The COMET Initiative database is a repository of studies relevant to the development of core outcome sets (COS). Use of the website continues to increase, with more than 16,500 visits in 2014 (36 % increase over 2013), 12,257 unique visitors (47 % increase), 9780 new visitors (43 % increase) and a rise in the proportion of visits from outside the UK (8565 visits; 51 % of all visits). By December 2014, a total of 6588 searches had been completed, with 2383 in 2014 alone (11 % increase). The growing awareness of the need for COS is reflected in the website and database usage figures. PMID- 26558999 TI - Controlled delivery of beta-globin-targeting TALENs and CRISPR/Cas9 into mammalian cells for genome editing using microinjection. AB - Tal-effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) proteins are genome editing tools with unprecedented potential. However, the ability to deliver optimal amounts of these nucleases into mammalian cells with minimal toxicity poses a major challenge. Common delivery approaches are transfection- and viral based methods; each associated with significant drawbacks. An alternative method for directly delivering genome-editing reagents into single living cells with high efficiency and controlled volume is microinjection. Here, we characterize a glass microcapillary-based injection system and demonstrate controlled co injection of TALENs or CRISPR/Cas9 together with donor template into single K562 cells for targeting the human beta-globin gene. We quantified nuclease induced insertions and deletions (indels) and found that, with beta-globin-targeting TALENs, similar levels of on- and off-target activity in cells could be achieved by microinjection compared with nucleofection. Furthermore, we observed 11% and 2% homology directed repair in single K562 cells co-injected with a donor template along with CRISPR/Cas9 and TALENs respectively. These results demonstrate that a high level of targeted gene modification can be achieved in human cells using glass-needle microinjection of genome editing reagents. PMID- 26559001 TI - Superior removal of arsenic from water with zirconium metal-organic framework UiO 66. AB - In this study, water stable zirconium metal-organic framework (UiO-66) has been synthesized and for the first time applied as an adsorbent to remove aquatic arsenic contamination. The as-synthesized UiO-66 adsorbent functions excellently across a broad pH range of 1 to 10, and achieves a remarkable arsenate uptake capacity of 303 mg/g at the optimal pH, i.e., pH = 2. To the best of our knowledge, this is the highest arsenate As(V) adsorption capacity ever reported, much higher than that of currently available adsorbents (5-280 mg/g, generally less than 100 mg/g). The superior arsenic uptake performance of UiO-66 adsorbent could be attributed to the highly porous crystalline structure containing zirconium oxide clusters, which provides a large contact area and plenty of active sites in unit space. Two binding sites within the adsorbent framework are proposed for arsenic species, i.e., hydroxyl group and benzenedicarboxylate ligand. At equilibrium, seven equivalent arsenic species can be captured by one Zr6 cluster through the formation of Zr-O-As coordination bonds. PMID- 26559002 TI - Guided Self-Assembly of Nano-Precipitates into Mesocrystals. AB - We show by a combination of computer simulation and experimental characterization guided self-assembly of coherent nano-precipitates into a mesocrystal having a honeycomb structure in bulk materials. The structure consists of different orientation variants of a product phase precipitated out of the parent phase by heterogeneous nucleation on a hexagonal dislocation network. The predicted honeycomb mesocrystal has been confirmed by experimental observations in an Mg-Y Nd alloy. The structure and lattice parameters of the mesocrystal and the size of the nano-precipitates are readily tuneable, offering ample opportunities to tailor its properties for a wide range of technological applications. PMID- 26559003 TI - The voltage-gated proton channel Hv1 is expressed in pancreatic islet beta-cells and regulates insulin secretion. AB - The voltage-gated proton channel Hv1 is a potent acid extruder that participates in the extrusion of the intracellular acid. Here, we showed for the first time, Hv1 is highly expressed in mouse and human pancreatic islet beta-cells, as well as beta-cell lines. Imaging studies demonstrated that Hv1 resides in insulin containing granules in beta-cells. Knockdown of Hv1 with RNA interference significantly reduces glucose- and K(+)-induced insulin secretion in isolated islets and INS-1 (832/13) beta-cells and has an impairment on glucose- and K(+) induced intracellular Ca(2+) homeostasis. Our data demonstrated that the expression of Hv1 in pancreatic islet beta-cells regulates insulin secretion through regulating Ca(2+) homeostasis. PMID- 26559000 TI - Neurobiological phenotypes associated with a family history of alcoholism. AB - BACKGROUND: Individuals with a family history of alcoholism are at much greater risk for developing an alcohol use disorder (AUD) than youth or adults without such history. A large body of research suggests that there are premorbid differences in brain structure and function in family history positive (FHP) individuals relative to their family history negative (FHN) peers. METHODS: This review summarizes the existing literature on neurobiological phenotypes present in FHP youth and adults by describing findings across neurophysiological and neuroimaging studies. RESULTS: Neuroimaging studies have shown FHP individuals differ from their FHN peers in amygdalar, hippocampal, basal ganglia, and cerebellar volume. Both increased and decreased white matter integrity has been reported in FHP individuals compared with FHN controls. Functional magnetic resonance imaging studies have found altered inhibitory control and working memory-related brain response in FHP youth and adults, suggesting neural markers of executive functioning may be related to increased vulnerability for developing AUDs in this population. Additionally, brain activity differences in regions involved in bottom-up reward and emotional processing, such as the nucleus accumbens and amygdala, have been shown in FHP individuals relative to their FHN peers. CONCLUSIONS: It is critical to understand premorbid neural characteristics that could be associated with cognitive, reward-related, or emotional risk factors that increase risk for AUDs in FHP individuals. This information may lead to the development of neurobiologically informed prevention and intervention studies focused on reducing the incidence of AUDs in high-risk youth and adults. PMID- 26559004 TI - Bacillus ectoiniformans sp. nov., a halotolerant bacterium isolated from deep-sea sediments. AB - A halotolerant, Gram-positive bacterium (strain NE-14T), which was isolated from sediment samples of the South China Sea, was subjected to a taxonomic study. Strain NE-14T grew well at wide temperature and pH ranges, 10.0-45.0 degrees C and pH 6-10, with an optimum at 30 degrees C and pH 8.0, respectively. Growth of strain NE-14T was observed at total salt concentrations of 0-10 % (w/v) with optimum at 2 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequence comparison indicated that the isolate belongs to the genus Bacillus. Strain NE 14T was related most closely to Bacillus shackletonii LMG 18435T, Bacillus bataviensis LMG 21833T, Bacillus idriensis SMC 4352-2T and Bacillus drentensis LMG 21831T with 16S rRNA gene sequence similarities of 96.2, 95.9, 95.8 and 95.7 %, respectively. DNA-DNA hybridization between strain NE-14T and B. shackletonii LMG 18435T, B. bataviensis LMG 21833T, B. idriensis SMC 4352-2T and B. drentensis LMG 21831T gave reassociation values of about 27.4, 22.4, 16.4 and 15.9 %, respectively. The DNA G+C content of strain NE-14T was 39.2 mol%. The predominant isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant cellular fatty acids of strain NE-14T were iso-C15 : 0 and anteiso C15 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phospholipid. Based on the phenotypic and phylogenetic characteristics, it is proposed that strain NE-14T be classified as representing a novel species of the genus Bacillus, for which the name Bacillus ectoiniformans sp. nov. is proposed. The type strain is NE-14T ( = DSM 28970T = JCM 30397T). PMID- 26559005 TI - Replacing DSM Categorical Analyses With Dimensional Analyses in Psychiatry Research: The Research Domain Criteria Initiative. PMID- 26559006 TI - Mobile diagnostics in outbreak response, not only for Ebola: a blueprint for a modular and robust field laboratory. AB - We established a modular, rapidly deployable laboratory system that provides diagnostic support in resource-limited, remote areas. Developed as a quick response asset to unusual outbreaks of infectious diseases worldwide, several of these laboratories have been used as part of the World Health Organization response to the Ebola virus outbreaks by teams of the 'European Mobile Lab' project in West Africa since March 2014. Within three days from deployment, the first European mobile laboratory became operational at the Ebola Treatment Unit (ETU) in Gueckedou, southern Guinea. Deployment in close proximity to the ETU decreased the turnaround time to an average of 4 h instead of several days in many cases. Between March 2014 and May 2015, more than 5,800 samples were tested in this field laboratory. Further EMLab units were deployed to Nigeria, Liberia and Sierra Leone in the following months of the Ebola outbreak. The technical concept of the EMLab units served as a blueprint for other mobile Ebola laboratories which have been set up in Mali, Cote d'Ivoire, Sierra Leone and other countries in West Africa. Here, we describe design, capabilities and utility of this deployable laboratory system for use in response to disease outbreaks, epidemiological surveillance and patient management. PMID- 26559007 TI - Faith-Based Organizations and Academic Global Surgery's Moral Imperative. PMID- 26559008 TI - Catheter Ablation of Ventricular Arrhythmias Arising from the Distal Great Cardiac Vein. AB - Catheter ablation of idiopathic ventricular arrhythmias arising from the distal great cardiac vein represents a great challenge. We report data regarding the electrocardiographic and electrophysiologic characteristics in two patients with ventricular arrhythmias arising from the distal great cardiac vein. The technical difficulties to advance and navigate the ablation catheter within the coronary venous system as well as the close proximity to the major coronary vessels are discussed. PMID- 26559009 TI - Invariant Versus Classical Quartet Inference When Evolution is Heterogeneous Across Sites and Lineages. AB - One reason why classical phylogenetic reconstruction methods fail to correctly infer the underlying topology is because they assume oversimplified models. In this article, we propose a quartet reconstruction method consistent with the most general Markov model of nucleotide substitution, which can also deal with data coming from mixtures on the same topology. Our proposed method uses phylogenetic invariants and provides a system of weights that can be used as input for quartet based methods. We study its performance on real data and on a wide range of simulated 4-taxon data (both time-homogeneous and nonhomogeneous, with or without among-site rate heterogeneity, and with different branch length settings). We compare it to the classical methods of neighbor-joining (with paralinear distance), maximum likelihood (with different underlying models), and maximum parsimony. Our results show that this method is accurate and robust, has a similar performance to maximum likelihood when data satisfies the assumptions of both methods, and outperform the other methods when these are based on inappropriate substitution models. If alignments are long enough, then it also outperforms other methods when some of its assumptions are violated. PMID- 26559011 TI - Agentic personality as mediator of social capital on developmental outcomes in the transition to adulthood: Evidence from Shanghai, China. AB - Drawing upon a sample of 1153 young people in Shanghai, China, this study investigates how agentic personality mediates between social capital embedded in a range of social contexts (family, friendship, association, and linking connection) and developmental outcomes during the transition to adulthood. The results of a structural equation modeling (SEM) analysis provide a good fit for the sample as a whole. The overall findings support the hypotheses that a higher level of agentic personality, including resilience, self-efficacy, and self esteem, is associated with higher levels of developmental outcomes. Agentic personality also mediates the effects of family, friendship, associational, and linking social capital on developmental outcomes. Family social capital is predictive of university students' identity achievement and academic achievement, but not of their mental health. Linking social capital is only predictive of identity achievement. Unexpectedly, friendship social capital and associational social capital are predictive of a lower level of academic achievement and mental health, respectively, despite their positive influences on all three developmental outcomes through their significant effects on agentic personality. The study provides empirical support for the importance of social capital in promoting young people's transition to adulthood. Implications for theory, practice, and policy are also discussed. PMID- 26559012 TI - Concern or confidence? Adolescents' identity capital and future worry in different school contexts. AB - This present study investigated the roles identity capital and school's socio economic status have on adolescent worry about future education, employment, and social status. The 354 participants were 14- to 15-year-old students from affluent (56.8%) and disadvantaged (43.2%) Finnish lower secondary schools. Structural equation modelling was used to test the hypothesis that a higher level of family-related identity capital is connected to a lower level of future worry, and that this connection is mediated through intrapersonal forms of identity capital, specifically academic self-concept and general self-efficacy. Adolescent future worry was also examined across school status with an independent samples t test. The findings suggest that, in the relatively equal societal context in Finland, adolescents are rather confident about their future education, employment, and social status regardless of the socio-economic status of the school they attend, and when their level of identity capital is high the future worry decreases further. PMID- 26559010 TI - The Phylogeny of Rickettsia Using Different Evolutionary Signatures: How Tree Like is Bacterial Evolution? AB - Rickettsia is a genus of intracellular bacteria whose hosts and transmission strategies are both impressively diverse, and this is reflected in a highly dynamic genome. Some previous studies have described the evolutionary history of Rickettsia as non-tree-like, due to incongruity between phylogenetic reconstructions using different portions of the genome. Here, we reconstruct the Rickettsia phylogeny using whole-genome data, including two new genomes from previously unsampled host groups. We find that a single topology, which is supported by multiple sources of phylogenetic signal, well describes the evolutionary history of the core genome. We do observe extensive incongruence between individual gene trees, but analyses of simulations over a single topology and interspersed partitions of sites show that this is more plausibly attributed to systematic error than to horizontal gene transfer. Some conflicting placements also result from phylogenetic analyses of accessory genome content (i.e., gene presence/absence), but we argue that these are also due to systematic error, stemming from convergent genome reduction, which cannot be accommodated by existing phylogenetic methods. Our results show that, even within a single genus, tests for gene exchange based on phylogenetic incongruence may be susceptible to false positives. PMID- 26559014 TI - Nondestructive nanofabrication on Si(100) surface by tribochemistry-induced selective etching. AB - A tribochemistry-induced selective etching approach is proposed for the first time to produce silicon nanostructures without lattice damage. With a ~1 nm thick SiOx film as etching mask grown on Si(100) surface (Si(100)/SiOx) by wet oxidation technique, nano-trenches can be produced through the removal of local SiOx mask by a SiO2 tip in humid air and the post-etching of the exposed Si in potassium hydroxide (KOH) solution. The material removal of SiOx mask and Si under low load is dominated by the tribochemical reaction at the interface between SiO2 tip and Si/SiOx sample, where the contact pressure is much lower than the critical pressure for initial yield of Si. High resolution transmission electron microscope (HRTEM) observation indicates that neither the material removal induced by tribochemical reaction nor the wet etching in KOH solution leads to lattice damage of the fabricated nanostructures. The proposed approach points out a new route in nondestructive nanofabrication. PMID- 26559013 TI - miR-490-5p suppresses tumour growth in renal cell carcinoma through targeting PIK3CA. AB - BACKGROUND INFORMATION: Dysregulated micro-RNAs have been reported in many human cancers, including renal cell carcinoma. Recent studies indicated that miR-490 is involved in tumour development and progression. However, the expression profile and function in renal cell carcinoma remains unknown. RESULTS: Herein, we showed that miR-490-5p was down-regulated in renal cell carcinoma tissues and cells compared with the adjacent normal tissues and normal cells. We also provided evidence that miR-490-5p acts as a tumour suppressor in renal carcinoma in a variety of in vitro and in vivo assays. Mechanistically, miR-490-5p was verified to directly bind to 3' UTR of the PIK3CA mRNA and reduce the expression of PIK3CA at both mRNA and protein levels, which further inhibits phosphatidylinositol 3 kinase/Akt signalling pathway. We further showed that knockdown of PIK3CA can block the growth inhibitory effect of miR-490-5p, and over-expression of PIK3CA can reverse the inhibitory effect of miR-490-5p on renal cancer cell tumourigenicity. CONCLUSIONS: Taken together, our results indicated for the first time that miR-490-5p functions as a tumour suppressor in renal carcinoma by targeting PIK3CA. SIGNIFICANCE: Our findings suggest that miR-490-5p may be a potential gene therapy target for the treatment of renal cell carcinoma. PMID- 26559015 TI - The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (ROTEM(r)) analysis. AB - We evaluated changes in rotational thromboelastometry (ROTEM((r)) ) parameters and clinical outcomes in patients undergoing total hip replacement arthroplasty, with concomitant infusions of tranexamic acid and of 6% hydroxyethyl starch 130/0.4. Fifty-five patients were randomly assigned to either the tranexamic acid (n = 29) or the control (n = 26) group. Hydroxyethyl starch was administered in the range of 10-15 ml.kg(-1) during the operation in both groups. In the control group, the clot formation time and maximum clot firmness of APTEM showed significant differences when compared with those of EXTEM at one hour postoperatively, suggestive of fibrinolysis. In the tranexamic acid group, there was no significant difference between each postoperative EXTEM and APTEM parameter. In the tranexamic acid and control group, postoperative blood loss was 308 ml (210-420 [106-745]) and 488 ml (375-620 [170-910], p = 0.002), respectively, and total blood loss was 1168 ml (922-1470 [663-2107]) and 1563 ml (1276-1708 [887-1494], p = 0.003). Haemoglobin concentration was higher in the tranexamic acid group on the second postoperative day (10.5 (9.4-12.1 [7.9-14.0]) vs. 9.6 (8.9-10.5[7.3-16.0]) g.dl(-1) , p = 0.027). In patients undergoing total hip replacement arthroplasty, postoperative fibrinolysis aggravated by hydroxyethyl starch was attenuated by co-administration of 10 mg.kg(-1) tranexamic acid, which may have led to less postoperative blood loss. PMID- 26559016 TI - Community health workers as chronic care coordinators: evaluation of an Australian Indigenous primary health care program. AB - OBJECTIVES: To explore how a client-centred Chronic Care model was implemented by Indigenous Health Workers (IHWs) at participating sites in a trial of IHW-led case management. To understand the experiences of engaging with the model from the perspective of the IHWs, health team members and clients. METHODS: The review was conducted within a cluster randomised trial of the model in six remote Indigenous communities in north Queensland over 18 months. Content analysis was undertaken on 377 project records of health worker activity. Descriptive coding was used to classify issues that were grouped under key themes. Open-ended interviews were conducted with 21 stakeholders and analysed using the key themes. RESULTS: Implementation of all elements of the intervention was not achieved. Key themes identified that describe the issues affecting the IHWs' capacity to implement the model were: service management, training, client engagement, clarification of IHW role and infrastructure. CONCLUSIONS: Placing skilled and dedicated IHWs to improve care coordination is insufficient to improve chronic disease outcomes. A supportive and systematic service delivery system is also required. IMPLICATIONS: The PHC model in remote Indigenous communities needs to be re-oriented to actively support the unique contributions of IHWs to chronic care coordination. PMID- 26559018 TI - Human resources for health development: toward realizing Universal Health Coverage in Japan. AB - Human resources are an important factor in establishing universal health coverage (UHC). We examined Japan's health policies related to development of human resources for health (HRH) toward establishing UHC, and tried to formulate a model for other countries wanting to introduce UHC through reviewing existing data and documents related to Japan's history in developing HRH. In the results, there were four phases of HRH development in Japan: Phase 1 involved a shortage of HRH; Phase 2 was characterized by rapid production of less-educated HRH; Phase 3 involved introduction of quality improvement procedures such as upgrade education for nursing staff or licensing examination for physicians; Phase 4 was characterized by a predominance of formal health professionals. To encourage transition between these phrases, Japan utilized several procedures, including: (i) offering shorter professional education, (ii) fewer admission requirements for professional education, (iii) widespread location of schools, and (iv) the aforementioned quality improvement procedures. Japan was able to introduce UHC during Phase 3, and Japanese health indicators have improved gradually through these phases. Consequently, the government of Japan focused on increasing the quantity of HRH through relaxed admission requirements, shorter education periods, and increasing the numbers of educational facilities, before introducing UHC. Subsequently, the government began focusing on improving quality through procedures such as upgrade education or licensing examination programs to enable less-educated HRH to become fully educated professionals. For governments wanting to introduce UHC, the Japanese model can be a suitable option for HRH development, particularly in resource-poor countries. PMID- 26559017 TI - Diffusion-weighted MRI for early detection and characterization of prostate cancer in the transgenic adenocarcinoma of the mouse prostate model. AB - PURPOSE: To improve early diagnosis of prostate cancer to aid clinical decision making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. MATERIALS AND METHODS: T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring. RESULTS: The ADC differentiated between control prostate ((1.86 +/- 0.20) * 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 +/- 0.10) * 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 +/- 0.18) * 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 +/- 0.06) * 10(-3) mm(2) /s) (P = 0.02). CONCLUSION: DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice. PMID- 26559019 TI - Associating liver partition and portal vein ligation (ALPPS): Taking a view of trails. AB - Associating liver partition and portal vein ligation (ALPPS) is introduced as a modified two-staged hepatectomy for advanced liver malignancies, which requires extended hepatectomy with very small future remnant liver volume. It is characterized by rapid and large growth of future remnant liver and potential of widening the indication of curative resection with extended major hepatectomy for liver malignancies. It showed, however, much higher morbidity and mortality than extended hepatectomy after portal vein embolization. Here, we review the literatures and examine the role of ALPPS in Japan, where zero mortality after hepatectomy is highly expected. PMID- 26559020 TI - A systematic review and meta-analysis of feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) versus two-stage hepatectomy (TSH). AB - This meta-analysis aimed to review the regeneration rate of future liver remnant (FLR) and perioperative outcomes after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two-stage hepatectomy (TSH). A web search was performed in "MEDLINE", "EMBASE", and "SCIENCE DIRECT" databases using both subject headings (MeSH) and truncated word to identify all the articles published that related to this topic. Pooled risk ratios were calculated for categorical variables and mean differences for continuous variables using the fixed-effects and random-effects models for meta-analysis. Three studies involved 282 patients, of whom 234 were in the TSH group and 48 in the ALPPS group. Morbidity was experienced in 56.3% patients in the ALPPS group and 36.1% in the TSH group. There was a statistical difference (RR = 1.08; Z = 3.24; 95% CI, p = 0.001). Second surgeries were performed successfully in 79.1% patients in the portal vein embolization (PVE) group and 100% in the ALPPS group. There was a statistical difference (Z = 2.48; 95% CI, p = 0.01). The mean regeneration rate of FLR in the ALPPS group was 56.4% compared with 52.8% in the TSH group. There was no statistical difference (95% CI, p = 0.34). So from the outcome of this meta-analysis, TSH had a similar remnant liver regeneration ability compared to ALPPS while the morbidity and mortality rates were relatively low. Cancer progression while waiting for the staged liver resection after portal vein embolization was a drawback for TSH. PMID- 26559021 TI - Transarterial Y90 radioembolization versus chemoembolization for patients with hepatocellular carcinoma: A meta-analysis. AB - Transarterial chemoembolization (TACE) is one of the standard locoregional treatments for intermediate stage hepatocellular carcinoma (HCC). Transarterial radioembolization (TARE) using beta-emitting yttrium-90 (90Y) integral to the glass matrix of the microspheres has been developed as an alternative to TACE in recent years. Thus, we conducted a meta analysis to evaluate the safety and efficacy of TARE versus TACE for unresectable HCC. We searched PubMed, EMBASE, Web of science and the Cochrane Library for clinical trials comparing TARE with TACE for unresectable HCC. Response rate, overall survival (OS), time to progression (TTP), hospitalization time days and clinical complications were analyzed and compared. Eight studies published from 2009 to 2014, with a total of 1,499 patients, were included in this meta-analysis. The pooled results showed that TARE (90Y) is significantly better in OS (HR = 0.74; 95% CI: 0.61-0.90), 3 year OS rates (RR = 1.75; 95% CI = 1.01-3.03, p = 0.05), TTP (HR = 0.61; 95% CI: 0.41-0.89), hospitalization time days (mean difference = -2.66; 95% CI: -4.08 - 1.24) and some complications (abdominal pain [RR = 0.30, 95% CI: 0.11-0.83, p = 0.02]) for patients with HCC, but did not affect tumor response (CR [RR = 1.06; 95% CI = 0.51-2.22], PR [RR = 1.24; 95% CI = 0.79-1.94], SD [RR = 1.13; 95% CI = 0.92-1.39], PD[RR = 0.75; 95% CI = 0.37-1.51], over-all tumor control [RR = 1.16; 95 % CI = 0.94-1.44]). The current meta-analysis suggests that TARE (Y90) is significantly better in OS, 3-year OS rates, TTP, hospitalization time days and some complications for patients with HCC. PMID- 26559022 TI - Adenovirus-mediated P311 inhibits TGF-beta1-induced epithelial-mesenchymal transition in NRK-52E cells via TGF-beta1-Smad-ILK pathway. AB - P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. In the present study, we constructed a recombinant adenovirus vector of p311 (called Ad-P311) and transferred it into rat renal proximal tubular epithelial cells (NRK-52E) to explore the effect of P311 on epithelial mesenchymal transition (EMT) of NRK-52E cells induced by TGF-beta1 and to elucidate its underlying mechanism against EMT. After successfully construction of Ad-P311 and transfer into NRK-52E cells, the proliferation and growth of P311 expressing cells was detected by MTT assay. TGF-beta1 was used to induce NRK-52E cells and Western blot analysis was used to examine the EMT markers (E-cadherin and alpha-smooth muscle actin (alpha-SMA)), signal transducers (p-Smad2/3 and Smad7). Integrin Linked Kinase (ILK) as a key intracellular mediator that controls TGF-beta1-induced-EMT was also assayed by Western blot analysis. The results showed that P311 transfection could significantly inhibit the proliferation and growth of TGF-beta1 induced NRK-52E cells. The results also showed that TGF-beta1 could induce EMT in NRK-52E cells through Smad-ILK signaling pathway with an increase in alpha-SMA, pSmad2/3 and ILK expression, and a decrease in E-cadherin and Smad7 expression. However, P311 efficiently blocked Smad-ILK pathway activation and attenuated all these EMT changes induced by TGF beta1. These findings suggest that P311 might be involved in the pathogenesis of renal fibrosis by inhibiting the EMT process via TGF-beta1-Smad-ILK pathway. P311 might be a novel target for the control of renal fibrosis and the progression of CKD. PMID- 26559023 TI - DHEA promotes osteoblast differentiation by regulating the expression of osteoblast-related genes and Foxp3(+) regulatory T cells. AB - Several studies have reported that dehydroepiandrosterone (DHEA) promotes osteoblast proliferation and inhibits osteoblast apoptosis and that DHEA inhibits osteoclast maturation. However, whether DHEA regulates osteoblast differentiation remains unclear. The present study first examined the effect of DHEA on bone morphology in vivo. DHEA was found to increase bone volume (BV), bone mineral density (BMD), and the number of trabeculae in bone (Th.N) and it was found to decrease trabecular spacing in bone (Th.sp) in ovariectomized (OVX) mice. Next, the effect of DHEA on osteoblast differentiation was examined in vitro and osteoblastogenesis-related marker genes, such as Runx2, Osterix, Collagen1, and Osteocalcin, were also detected. DHEA increased osteoblast production in mesenchymal stem cells (MSCs) cultured in osteoblastogenic medium, and DHEA increased the expression of Runx2 and osterix, thereby increasing the expression of osteocalcin and collagen1. Immune cells and bone interact, so changes in immune cells were detected in vivo. DHEA increased the number of Foxp3(+) regulatory T cells (Tregs) in the spleen but it did not affect CTLA-4 or IL-10. When MSCs were treated with DHEA in the presence of Tregs, alkaline phosphatase (ALP) activity increased. Osteoblasts and adipocytes are both generated by MSCs. If osteoblast differentiation increases, adipocyte differentiation will decrease, and the reverse also holds true. DHEA was found to increase the number of adipocytes in osteoblastogenic medium but it had no effect on the number of adipocytes and expression of PPARgamma mRNA in adipogenic medium. This finding suggests that osteoblasts may be involved in adipocyte production. In conclusion, the current results suggest that DHEA can improve postmenopausal osteoporosis (PMO) by up-regulating osteoblast differentiation via the up-regulation of the expression of osteoblastogenesis-related genes and via an increase in Foxp3(+) Tregs. PMID- 26559024 TI - Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis. AB - Oleanolic acid (3beta-hydroxyolean-12-en-28-oic acid, OA) is a naturally occurring triterpenoid with various promising pharmacological properties. The present study was conducted to determine the protective effects of OA against oxidized low-density lipoprotein (ox-LDL) induced endothelial cell apoptosis and the possible underlying mechanisms. Our results showed that ox-LDL significantly decreased cell viability and induced apoptosis in human umbilical vein endothelial cells (HUVECs). OA in the co-treatment showed a protective effect against ox-LDL induced loss in cell viability and an increase in apoptosis, which was associated with the modulating effect of OA on ox-LDL induced hypoxia inducible factor 1alpha(HIF-1alpha) expression. Moreover, our results showed that the modulating effect of OA against ox-LDL induced HIF-1alpha expression was obtained via inhibition of lipoprotein receptor 1 (LOX-1)/reactive oxygen species (ROS) signaling. Collectively, we suggested that the protective effect of OA against ox-LDL induced HUVEC apoptosis might, at least in part, be obtained via inhibition of the LOX-1/ROS/HIF-1alpha signaling pathway. PMID- 26559025 TI - Decrease of ZEB1 expression inhibits the B16F10 cancer stem-like properties. AB - Increasing evidence supports that cancer stem cells (CSCs) are responsible for driving tumor initiation and maintenance. Zinc-finger E-box binding homeobox 1 (ZEB1) is a transcription factor for regulating tumor progression, and contributes to maintenance of CSC-like properties. The goal of the present study is to investigate the effect of decreasing ZEB1 expression on the B16F10 CSC-like properties. The recombinant shRNA targeting ZEB1 were transfected into melanoma B16F10 cells, and shZEB1-CD133(+)CD44(+) CSCs were isolated from the stable transfected cells using the magnetic-associated cell sorting method. The shZEB1 CD133(+)CD44(+) CSC-like properties were systematically analyzed. The results show the B16F10 shZEB1-CD133(+)CD44(+) CSCs significantly decreased the ability of clonogenicity, cellular proliferation, migration, and invasion. Importantly, tumorigenicity and tumor lung metastasis was significantly inhibited in B16F10 shZEB1-CD133(+)CD44(+) CSCs compared with B16F10 scramble-CD133(+)CD44(+) CSCs. The decrease of ZEB1 expression markedly resulted in down-regulation of vimentin and N-cadherin expression as well as up-regulation of E-cadherin expression in tumor tissues from the mice injected with B16F10 shZEB1-CD44(+)CD133(+) CSCs. These findings contribute to understanding the maintenance of B16F10 CD133(+)CD44(+) CSC-like properties that was closely associated with ZEB1 expression. ZEB1 may serve as a new therapeutic target for treatment of malignant melanoma. PMID- 26559026 TI - The risk factors for suboptimal CD4 recovery in HIV infected population: an observational and retrospective study in Shanghai, China. AB - Although the initiation of antiretroviral therapy (ART) has promoted the reconstitution of CD4+ T-cell count in the HIV infected population, not all patients can achieve the normalization of their immunologic functions. We analysed the variables associated with immunologic recovery, which is commonly regarded as the increase of CD4 to 350 cell/MUL after a year of ART. We collected data from 3,485 patients attending a university-based HIV clinic from June 2005 to July 2014 in Shanghai, China. Logistic regression test was performed to analyse the risk factors for suboptimal CD4+ recovery following yearlong ART. The CD4+ T-cell of 723 participants (41.5% of the 1744 subjects) showed more than 350 cell/MUL after one year of ART. Compared with baseline CD4 > 350 cell/MUL, patients with baseline CD4 <= 200 cell/MUL or 200 < CD4 <= 350 cell/MUL were 42.6, 4.5 times more likely to be incomplete CD4 recovery, respectively. The risk of suboptimal immunologic recovery among patients with regimen including AZT or d4T were 2.1, 2.4 times higher compared with TDF, respectively. In our study, between optimal CD4 recovery group and suboptimal recovery group, there were no significant differences in age, gender, marital status, transmission routes, WHO stage, and CD4 recovery rates. As for the dynamic CD4 change, we found the CD4 recovery rates were 49.9% and 61.8% in the second and third year of ART, respectively. Patients who had a low level of CD4+ T-cell count (< 200 cell/MUL) during the initiation of ART exhibited more difficulties recovering to a normal level. Furthermore, the regimen, including AZT or d4T, was not beneficial to CD4 recovery. So, more efforts should be made to guarantee the early diagnosis and timely treatment for HIV/AIDS patients, and simultaneously optimize antiretroviral therapy. PMID- 26559027 TI - Serum concentrations of Flt-3 ligand in rheumatic diseases. AB - Fms-like tyrosine kinase 3 (Flt-3) is a cytokine receptor expressed on the surface of bone-marrow progenitor of hematopoietic cells. Flt-3 ligands are produced by peripheral blood mononuclear cells, and found in various human body fluids. Flt-3 signal is involved in the regulation of vessel formation as well as B cell differentiation, suggesting that Flt-3 signal contributes to the pathogenesis of vascular abnormalities and immune dysregulation in rheumatic diseases. The aim of the present study is to examine serum Flt-3 ligand levels in patients with various rheumatic diseases, and to evaluate the possibility that serum Flt-3 ligand levels can be a useful disease marker. Sera were obtained from 20 dermatomyositis (DM) patients, 36 systemic sclerosis (SSc) patients, 10 systemic lupus erythematosus (SLE) patients, 10 scleroderma spectrum disorder (SSD) patients, 4 mixed connective tissue disease (MCTD) patients, and 12 normal subjects. Flt-3 ligand levels were determined with ELISA. Serum Flt-3 ligand levels were significantly elevated in patients with DM, SSc, SSD and MCTD compared to those in normal subjects. DM patients with elevated Flt-3 ligand levels were accompanied with significantly increased CRP levels and increased frequency of heliotrope rash than those with normal levels. In addition, SSc patients with elevated Flt-3 ligand levels showed significantly reduced frequency of nailfold bleeding. Serum Flt-3 ligand levels can be a marker of cutaneous manifestation in DM and a marker of microangiopathy in SSc. Clarifying the role of Flt-3 ligand in rheumatic diseases may lead to further understanding of these diseases and new therapeutic approaches. PMID- 26559028 TI - Fluorescent Biotin Analogues for Microstructure Patterning and Selective Protein Immobilization. AB - Benzyl substitution on ureido nitrogens of biotin led to manifestation of aggregation-induced emission, which was studied by steady-state fluorescence, microscopy, and TD-DFT, providing a rationale into the observed photophysical behavior. Besides exhibiting solvatochromism, the biotin derivatives revealed emission peaks centered at ~430 and 545 nm, which has been attributed to the pi pi stacking interactions. Our TD-DFT results also correlate the spectroscopic data and quantify the nature of transitions involved. The isothermal titration calorimetry data substantiates that the binding of the biotin derivatives with avidin are pretty strong. These derivatives on lithographic patterning present a platform for site specific strept(avidin) immobilization, thus opening avenues for potential applications exploiting these interactions. The fluorescent biotin derivatives can thus find applications in cellular biology and imaging. PMID- 26559029 TI - Remote Construction of Chiral Vicinal Tertiary and Quaternary Centers by Catalytic Asymmetric 1,6-Conjugate Addition of Prochiral Carbon Nucleophiles to Cyclic Dienones. AB - An unprecedented remote construction of chiral vicinal tertiary and quaternary centers by a catalytic asymmetric 1,6-conjugate addition of prochiral carbon nucleophiles to cyclic dienones has been developed. Both 5H-oxazol-4-ones and 2 oxindoles were found to be very efficient carbon nucleophiles in this reaction at a remote position, giving products with excellent enantio- and diastereoselectivities (up to 99% ee and >19:1 d.r. for 5H-oxazol-4-ones and up to 97% ee and >19:1 d.r. for 2-oxindoles). PMID- 26559030 TI - Hierarchical Nitrogen-Doped Graphene/Carbon Nanotube Composite Cathode for Lithium-Oxygen Batteries. AB - The lithium-oxygen (Li-O2 ) battery is a very appealing candidate for advanced high energy applications owing to its exceptionally high specific energy. However, its poor energy efficiency, rate capability, and cyclability remain key barriers to its practical application. In this work, using a rationally designed cathode based on a bimodal mesoporous nitrogen-doped graphene/carbon nanotube (NGC) composite, we have developed a Li-O2 battery demonstrating enhanced round trip efficiency (ca. 85 %) and excellent cyclability over 400 cycles under a high current rate of 500 mA g(-1) . The excellent cyclability and rate capability are attributed to improved stability of the aggressive LiO2 intermediate on the nitrogen-doped carbon surface in addition to the favorable hierarchical architecture of NGC. These results demonstrate a valuable research direction to achieve highly stable and reversible Li-O2 batteries through tuning the surface chemistry of the cathode in addition to finding a stable electrolyte solvent. PMID- 26559031 TI - New efficiencies in the NHS-how shall we recognize them? PMID- 26559032 TI - Counting practice: the impact of information systems on community nursing. AB - The act of collecting data is not neutral, it exerts an influence on the activity it is intended to reflect. This paper examines three basic assumptions which underpin the collection of information for minimum data-sets from community nurses, and suggests that influence has the potential to drive practitioners towards a model of practice which is fundamentally flawed. The paper criticizes the use of a single episode of care as the base unit of activity in a long-term, continuing service. It argues that the focus on single individuals as recipients of a service is inappropriate for family- or community-based nursing. Further, it challenges the idea that the complex, multi-faceted and compound interactions encompassed within community nursing practice can be separated into single activities to be counted or measured. It concludes that identified deficiencies in the information systems stem from an inadequate base of theoretical knowledge, and not from personal failings on the part of managers or their staff. It warns that the inappropriate basis for collecting information may promote insensitive and ineffective community nursing practice. PMID- 26559033 TI - Integrating nurse education with higher education. PMID- 26559034 TI - Nurse management-a case of competing rationalities. AB - Nurse management has been characterized by problems throughout its development. Through the application of a Weberian theoretical framework the origins of these problems are identified and their influence on the current situation discussed. The suggestion is that the difficulties of nurse management arise from an inherent conflict between the notions of caring and management. This must be resolved if nurses are to be effective health care managers and are to safeguard the interests of patients. PMID- 26559035 TI - The increasing differentiation of the Health Service. PMID- 26559036 TI - Increasing concern is expressed over stress in the workplace. How far should stress management be a responsibility of individuals or organizations? PMID- 26559037 TI - Satisfaction with nursing care and work during a year of clinical supervision and individualized care. Comparison between two wards for the care of severely demented patients. AB - An intervention study was set up to explore the effects of the implementation of planned individualized care and regular systematic clinical supervision regarding nurses' degree of satisfaction with nursing care and work. All nurses on two similar wards caring for severely demented patients participated as experimental ward (EW) (n = 19) and control ward (CW) (n = 20). Data were collected before intervention and at 6 months and 12 months during intervention, by means of a questionnaire developed in Sweden which assesses aspects of satisfaction with nursing care and work. Analysis was performed by means of principal component analysis, Wilcoxon rank sum test and Friedman two-way ANOVA. The baseline data showed no significant differences in the responses from the nurses on the two wards; they were found to be more satisfied than dissatisfied with their job although recognition from management was poor. During the intervention, the experimental ward nurses' experience of praise, professional growth, autonomy and quality of care, as well as their feeling of co-operation with colleagues and comfort improved significantly, while no changes occurred on the control ward. The quality of the written documentation on patients' needs and care improved significantly, and the experimental ward nurses also rejected significantly more strongly that their knowledge about patients and work was unsatisfactory. Their improved satisfaction with nursing care and work was believed to be related to the support they received in cognitive and emotional coping, the possibility of reflective learning and the change in management style associated with intervention. PMID- 26559039 TI - Double single-port procedure for transanal intersphincteric proctectomy and abdominal ileorectal anastomosis - a video vignette. PMID- 26559040 TI - Is Australasia producing too many emergency physicians? Yes. PMID- 26559042 TI - Controlling droplet-based deposition uniformity of long silver nanowires by micrometer scale substrate patterning. AB - We report control of droplet-deposit uniformity of long silver nanowires suspended in solutions by microscopic influence of the liquid contact line. Substrates with microfabricated line patterns with a pitch far smaller than mean wire length lead to deposit thickness uniformity compared to unpatterned substrates. For high boiling-point solvents, two significant effects were observed: The substrate patterns suppressed coffee ring staining, and the wire deposits exhibited a common orientation lying perpendicular over top the lines. The latter result is completely distinct from previously reported substrate groove channeling effects. This work shows that microscopic influence of the droplet contact line geometry including the contact angle by altered substrate wetting allows significant and advantageous influence of deposition patterns of wire-like solutes as the drop dries. PMID- 26559041 TI - Signal dependent ER export of lemur tyrosine kinase 2. AB - BACKGROUND: The membrane anchored kinase, LMTK2, is a serine/threonine kinase predominantly localized to endosomal compartments. LMTK2 has been shown to be involved in the trafficking of the CFTR ion channel, the androgen receptor, as well as modulating neurodegeneration. As a membrane anchored protein, LMTK2 must be exported from the ER, yet the mechanisms whereby LMTK2 is sequestered within the ER for efficient export are unknown. METHODS: Sequence analysis of the carboxyl tail of LMTK2 revealed a putative di-acidic ER export motif. Site directed mutagenesis was utilized to ablate this potential motif. Subcellular fractionation, immunofluorescence microscopy, and transferrin recycling assays were used to determine the consequence of mutating LMTK2's export motif. RESULTS: Mutation of the di-acidic export motif led to ER retention of LMTK2, and an increase in protein half-life and a concomitant loss of LMTK2 from its appropriate terminal destination. Loss of LMTK2 from endosomal compartments by preventing its release from the ER is linked to a reduction in transferrin recycling. CONCLUSIONS: We have identified a di-acidic ER export motif within the carboxyl tail of the membrane anchored kinase LMTK2. This sequence is used by LMTK2 for its efficient export from the ER. PMID- 26559043 TI - New understanding of nonconvulsive status epilepticus in adults: treatments and challenges. AB - Nonconvulsive status epilepticus (NCSE) in adults represents a constellation of conditions producing ongoing ictal impairment with myriad clinical presentations. These may vary from minimal obtundation, to psychosis to coma for which electroencephalography is essential to diagnosis. Treatment is highly variable and is tailored to the level of consciousness, probable outcome and underlying etiology. There is a new and emerging understanding of the nature of NCSE, its classification and the challenges in treatment. The aim of this article is to review the classic and most recent literature on NCSE in adults focusing attention on the clinical settings in which NCSE frequently occurs, in order to improve awareness of the issues involved in electroclinical diagnosis, treatment and prognostication. PMID- 26559044 TI - Pneumo-orbita mimicking hordeolum. PMID- 26559045 TI - Two-State Intramolecular Charge Transfer (ICT) with 3,5-Dimethyl-4 (dimethylamino)benzonitrile (MMD) and Its Meta-Isomer mMMD. Ground State Amino Twist Not Essential for ICT. AB - From X-ray structure analysis, amino twist angles of 90.0 degrees for 2,4 dimethyl-3-(dimethylamino)benzonitrile (mMMD), 82.7 degrees for 4-(di-tert butylamino)benzonitrile (DTABN), and 88.7 degrees for 6-cyanobenzoquinuclidine (CBQ) are determined, all considerably larger than the 57.4 degrees of 3,5 dimethyl-4-(dimethylamino)benzonitrile (MMD). This large twist leads to lengthening of the amino-phenyl bond, 143.5 pm (mMMD), 144.1 pm (DTABN), 144.6 pm (CBQ), and 141.4 pm (MMD), as compared with 136.5 pm for the planar 4 (dimethylamino)benzonitrile (DMABN). As a consequence, the electronic coupling between the amino and phenyl subgroups in mMMD, DTABN, CBQ, and MMD is much weaker than in DMABN, as seen from the strongly reduced molar absorption coefficients. The fluorescence spectrum of MMD in n-hexane at 25 degrees C consists of two emissions, from a locally excited (LE) and an intramolecular charge transfer (ICT) state, with a fluorescence quantum yield ratio Phi'(ICT)/Phi(LE) of 12.8. In MeCN, a single ICT emission is found. With mMMD in n-hexane, in contrast, only LE fluorescence is observed, whereas the spectrum in MeCN originates from the ICT state. These differences are also seen from the half widths of the overall fluorescence bands, which in n-hexane are larger for MMD than for mMMD, decreasing with solvent polarity for MMD and increasing for mMMD, reflecting the disappearance of LE and the onset of ICT in the overall spectra, respectively. From solvatochromic measurements the dipole moments MUe(ICT) of MMD (16 D) and mMMD (15 D) are obtained. Femtosecond excited state absorption (ESA) spectra at 22 degrees C, together with the dual (LE + ICT) fluorescence, reveal that MMD in n-hexane undergoes a reversible LE ? ICT reaction, with LE as the precursor, with a forward rate constant ka = 5.6 * 10(12) s(-1) and a back reaction kd ~ 0.05 * 10(12) s(-1). With MMD in the strongly polar solvent MeCN, ICT is faster: ka = 10 * 10(12) s(-1). In the case of mMMD in n-hexane, the ESA spectra show that ICT does not take place, contrary to MeCN, in which ka = 2.5 * 10(12) s(-1). The ICT reactions with MMD and mMMD are much faster than that of the parent compound DMABN in MeCN, with ka = 0.24 * 10(12) s(-1). Because of the very short ICT reaction times of 180 fs (MMD, n-hexane), 100 fs (MMD, MeCN), and 400 fs (mMMD, MeCN), it is clear that the picosecond fluorescence decays of these systems appear to be single exponential, due to the insufficient time resolution of 3 ps. It is concluded that the faster LE -> ICT reaction of MMD as compared with DMABN (ka = 0.24 * 10(12) s(-1) in MeCN) is caused by a smaller energy gap DeltaE(S1,S2) between the lowest singlet excited states and not by the large amino twist angle. Similarly, the larger DeltaE(S1,S2) of mMMD as compared with MMD is held responsible for its smaller ICT efficiency (no reaction in n-hexane). PMID- 26559046 TI - The Baykal phenomenon: large congenital melanocytic nevi involving the breast tend to spare the nipple and areola. PMID- 26559047 TI - Switching Transient Generation in Surface Interrogation Scanning Electrochemical Microscopy and Time-of-Flight Techniques. AB - In surface interrogation scanning electrochemical microscopy (SI-SECM), fine and accurate control of the delay time between substrate generation and tip interrogation (tdelay) is crucial because tdelay defines the decay time of the reactive intermediate. In previous applications of the SI-SECM, the resolution in the control of tdelay has been limited to several hundreds of milliseconds due to the slow switching of the bipotentiostat. In this work, we have improved the time resolution of tdelay control up to ca. 1 MUs, enhancing the SI-SECM to be competitive in the time domain with the decay of many reactive intermediates. The rapid switching SI-SECM has been implemented in a substrate generation-tip collection time-of-flight (SG-TC TOF) experiment of a solution redox mediator, and the results obtained from the experiment exhibited good agreement with that obtained from digital simulation. The reaction rate constant of surface Co(IV) on oxygen-evolving catalyst film, which was inaccessible thus far due to the lack of tdelay control, has been measured by the rapid switching SI-SECM. PMID- 26559048 TI - Stochastic model explains formation of cell arrays on H/O-diamond patterns. AB - Cell migration plays an important role in many biological systems. A relatively simple stochastic model is developed and used to describe cell behavior on chemically patterned substrates. The model is based on three parameters: the speed of cell movement (own and external), the probability of cell adhesion, and the probability of cell division on the substrate. The model is calibrated and validated by experimental data obtained on hydrogen- and oxygen-terminated patterns on diamond. Thereby, the simulations reveal that: (1) the difference in the cell movement speed on these surfaces (about 1.5*) is the key factor behind the formation of cell arrays on the patterns, (2) this difference is provided by the presence of fetal bovine serum (validated by experiments), and (3) the directional cell flow promotes the array formation. The model also predicts that the array formation requires mean distance of cell travel at least 10% of intended stripe width. The model is generally applicable for biosensors using diverse cells, materials, and structures. PMID- 26559049 TI - Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists: a self-controlled register study. AB - ESSENTIALS: It is not known if initiation of glucose-lowering drugs alters the efficacy of vitamin K antagonists (VKA). We examined if glucose-lowering drugs affected international normalized ratio (INR) in VKA-treated patients. Upon initiating glucose-lowering drugs, 51% of patients had INR values below the therapeutic window. Monitoring of INR levels should be intensified upon initiation of glucose-lowering drugs. BACKGROUND: It is not known whether initiation of antidiabetic treatment affects the effect of vitamin K antagonists (VKAs). It was previously shown that metformin affects the effect of one VKA, phenprocoumon. OBJECTIVES: The aim of this study was to determine if initiation of glucose-lowering treatment affects the international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients commencing glucose-lowering treatment while being treated with warfarin or phenprocoumon were included in the study. We compared INR, dose/INR and proportion of patients with at least one sub-therapeutic INR measurement before and after initiation of glucose-lowering treatment. RESULTS: Initiation of glucose-lowering treatment caused mean INR to decrease from 2.5 to 2.2 (decrease of -0.3 [95% CI: -0.1; -0.5]) and led to more than half of the patients having at least one sub-therapeutic INR measurement. Six to 12 weeks later, the VKA dose/INR was increased by 11%, indicating a weakened effect of the VKA. CONCLUSION: Initiation of glucose-lowering treatment reduces the anticoagulant effect of VKAs to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. PMID- 26559050 TI - Black Jobs Matter: Racial Inequalities in Conditions of Employment and Subsequent Health Outcomes. AB - African-Americans shoulder an excessive burden of unemployment, precarious employment, and low paying jobs in the United States, which may help explain why they experience some of the worst health outcomes among U.S. citizens. This paper presents a conceptual framework describing this phenomenon. The social determinants of health as described by this framework include racism, social and public policy formation, socioeconomic status, and conditions of employment. The intermediate determinants of health, which include the ability to afford health behavior, depression and addiction, environmental exposures, and access to primary care, are informed by conditions of employment, which leads to poor health outcomes for African-Americans. This paper will explore in detail these relationships. PMID- 26559051 TI - Prevalence and Patterns of Tobacco Use in Bangladesh from 2009 to 2012: Evidence from International Tobacco Control (ITC) Study. AB - BACKGROUND: Smoking and passive smoking are collectively the biggest preventable cause of death in Bangladesh, with major public health burden of morbidity, disability, mortality and community costs. The available studies of tobacco use in Bangladesh, however, do not necessarily employ nationally representative samples needed to monitor the problem at a national scale. This paper examines the prevalence and patterns of tobacco use among adults in Bangladesh and the changes over time using large nationally representative comparable surveys. METHODS: Using data from two enumerations of the International Tobacco Control (ITC) Bangladesh Project conducted in 2009 and 2012, prevalence estimates are obtained for all tobacco products by socio-economic determinants and sample types of over 90,000 individuals drawn from over 30,000 households. Household level sample weights are used to obtain nationally representative prevalence estimates and standard errors. Statistical tests of difference in the estimates between two time periods are based on a logistic regression model that accounts for the complex sampling design. Using a multinomial logit model, the time trend in tobacco use status is identified to capture the effects of macro level determinants including changes in tobacco control policies. RESULTS: Between 2009 and 2012, overall tobacco use went down from 42.4% to 36.3%. The decline is more pronounced with respect to smokeless tobacco use than smoking. The prevalence of exclusive cigarette smoking went up from 7.2% to 10.6%; exclusive bidi smoking remained stable at around 2%; while smoking both cigarette and bidi went down from 4.6% to 1.8%; exclusive smokeless tobacco use went down from 20.2% to 16.9%; and both smokeless tobacco use and smoking went down from 8.4% to 5.1%. In general, the prevalence of tobacco use is higher among men, increases from younger to older age groups, and is higher among poorer people. Smoking prevalence is the highest among the slum population, followed by the tribal population, the national population and the border area population, suggesting greater burden of tobacco use among the disadvantaged groups. CONCLUSIONS: The overall decline in tobacco use can be viewed as a structural shift in the tobacco market in Bangladesh from low value products such as bidi and smokeless tobacco to high value cigarettes, which is expected with the growth in income and purchasing power of the general population. Despite the reduction in overall tobacco use, the male smoking prevalence in Bangladesh is still high at 37%. The world average of daily smoking among men is 31.1%. The Tobacco Control Act 2005 and the Amendment have yet to make a significant impact in curbing tobacco usage in Bangladesh. The findings in this paper further suggest that the tobacco control policies in Bangladesh need to include targeted interventions to restrain the use of particular types of tobacco products among specific demographic and socio-economic groups of the population, such as smoked tobacco among men, smokeless tobacco among women, and both smoked and smokeless tobacco among those living in rural areas, those in low socio-economic status and those belonging to the tribal and the slum population. PMID- 26559052 TI - Biomedical applications of microneedles in therapeutics: recent advancements and implications in drug delivery. AB - INTRODUCTION: The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc. AREAS COVERED: This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered. EXPERT OPINION: This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future. PMID- 26559053 TI - Current Issues in Molecular Catalysis Illustrated by Iron Porphyrins as Catalysts of the CO2-to-CO Electrochemical Conversion. AB - Recent attention aroused by the reduction of carbon dioxide has as main objective the production of useful products, the "solar fuels", in which solar energy would be stored. One route to this goal is the design of photochemical schemes that would operate this conversion using directly sun light energy. An indirect approach consists in first converting sunlight energy into electricity then using it to reduce CO2 electrochemically. Conversion of carbon dioxide into carbon monoxide is thus a key step through the classical dihydrogen-reductive Fischer Tropsch chemistry. Direct and catalytic electrochemical CO2 reduction already aroused active interest during the 1980-1990 period. The new wave of interest for these matters that has been growing since 2012 is in direct conjunction with modern energy issues. Among molecular catalysts, electrogenerated Fe(0) porphyrins have proved to be particularly efficient and robust. Recent progress in this field has closely associated the search of more and more efficient catalysts in the iron porphyrin family with an unprecedentedly rigorous deciphering of mechanisms. Accordingly, the coupling of proton transfer with electron transfer and breaking of one of the two C-O bonds of CO2 have been the subjects of relentless scrutiny and mechanistic analysis with systematic investigation of the degree of concertedness of these three events. Catalysis of the electrochemical CO2-to-CO conversion has thus been a good testing ground for the mechanism diagnostic strategies and the all concerted reactivity model proposed then. The role of added Bronsted acids, both as H-bond providers and proton donors, has been elucidated. These efforts have been a preliminary to the inclusion of the acid functionalities within the catalyst molecule, giving rise to considerable increase of the catalytic efficiency. The design of more and more efficient catalysts made it necessary to propose "catalytic Tafel plots" relating the turnover frequency to the overpotential as a rational way of benchmarking the catalysts within iron porphyrins and among all available molecular catalysts, independently of the characteristics of the electrolytic cell in use. To be reliable, such assignments of the intrinsic characteristics of catalysts are grounded in the accurate elucidation of mechanisms. Without forgetting the importance of large scale electrolysis, not only mobilization of all resources of nondestructive techniques such as cyclic voltammetry was necessary to achieve this challenge, but also new approaches, such as foot-of-the-wave analysis combined with raising of scan rate, had to be applied. The latest improvement in catalyst design was to render it water-soluble while preserving, or even augmenting, its catalytic efficiency. The replacement of the nonaqueous solvents so far used by water makes the CO2-to-CO half-cell reaction much more attractive for applications, allowing its association with a water-oxidation anode through a proton-exchange membrane. Manipulation of pH and buffering then allow CO2-to-CO conversions from those involving complete CO-selectivity to ones with prescribed CO-H2 mixtures. Overall, it appears that not only are iron porphyrins the most efficient catalysts of the CO2-to-CO electrochemical conversion but also they can serve to illustrate general issues concerning the field of molecular catalysis as a whole, including other reductive or oxidative processes. PMID- 26559054 TI - Corticosteroid Risk Function of Severe Infection in Primary Immune Thrombocytopenia Adults. A Nationwide Nested Case-Control Study. AB - Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n degrees 4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61-3.83). The dose-effect relation showed that the risk existed from averaged daily doses >=5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17-3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses. PMID- 26559056 TI - Erratum to: Age-related delay in urinary stone clearance in elderly patients with solitary proximal ureteral calculi treated by extracorporeal shock wave lithotripsy. PMID- 26559055 TI - Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance. AB - PURPOSE: To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. METHODS: A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40-64, 65-74 and >= 75 years were calculated in the diabetic patients and the non diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1-2.9 years, 3-4.9 years and >= 5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively. RESULTS: The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3-2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1-2.9 years, 3-4.9 years and >= 5 years was 1.5 (0.8-2.7), 1.6 (1.0-2.4), 1.6 (1.1-2.4) and 1.7 (1.3-2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. CONCLUSIONS: Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer. PMID- 26559057 TI - Epidemiology of bladder stone of children: precipitating events. AB - Urological surgery evolved from the ancient practice of removing primary bladder stones from young boys. Bladder stones, once ubiquitous, long ago disappeared from the developed world while pockets of disease still exist in developing countries. Two epidemiological studies identified as precipitating events of bladder stone formation the practice of substitutive carbohydrate feedings to newborns. In Southeast Asia, masticated rice is fed to newborns in stone-endemic villages while in England, during the eighteenth and nineteenth centuries pap or panada was used to hand-feed infants when breast milk was not available. Fresh milk from dairy animals was deemed preferable to pap. Lack of access to dairy cattle enhanced need for hand-feeding. In an epidemiological study, during mid nineteenth century in England the prevalence of dairy cattle was inversely related to the prevalence of bladder stones. These epidemiological data relate stone formation to nutrition during the first few days or weeks of life. It is surmised that frequent use of or exclusive reliance on carbohydrate foods replacing milk feedings leads to a relative dietary deficiency in phosphates and the formation of insoluble urinary salts. Girls, with short, nontortuous urethras may pass much of the calculus debris without retaining nuclei in the bladder. In some males, stone nuclei are formed and retained. The growth of stones is determined thereafter by the net effect of depository and resorptive mechanisms operating over time distributing over many years the age that patients present for surgical stone removal. The role of early introduction of carbohydrate foods and reduced milk intake of neonates has not been incorporated into recommendations for feeding newborns in endemic countries nor comprehensively modeled in animals. PMID- 26559059 TI - Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization. AB - CONTEXT: Docosahexanoic acid (DHA) is an essential omega-3 fatty acid for normal brain development and its use has increased considerably in recent years. OBJECTIVE: The aim of this study is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of DHA for improved palatability, dispersibility and bioavailability. METHODS: The SNEDDS were prepared and evaluated for miscibility, employing different combinations of olive oil and soyabean oil as oil phase, Span 80, Span 20, soya phosphatidylcholine, Labrafil M 1944 CS as surfactants while Tween 80, PEG 400, Cremophor RH40 and propylene glycol as cosurfactants. Thermodynamically stable SNEDDS were characterized for dispersibility, self-emulsification time, droplet size, zeta potential along with sensory analysis. The optimized formulation was subjected to ex vivo and in vivo evaluation such as intestinal permeability, memory performance test, brain concentration and histopathology studies. RESULTS: The optimized SNEDDS formulation showed emulsification time of 27 +/- 4.7 s with droplet size of 17.6 +/- 3.5 nm and zeta potential of -37.6 +/- 0.5 mV. Intestinal absorption study depicted 18.3%, 21.5%, 41.5%, 98.7% absorption of DHA with SNEDDS-based formulation in comparison to 8.2%, 15.1%, 28.8%, 46.1% absorption of DHA with oil based marketed formulation after 0.5, 1, 2 and 4 h. DHA concentration in brain homogenate was found to be increased to 2.6-fold in comparison to DHA-marketed formulation. This could be ascribed to enhanced dispersibility and bioavailability of DHA from nanosized formulation. CONCLUSION: The developed formulation led to enhanced dispersibility and bioavailability of DHA due to the formation of nanodroplets. PMID- 26559058 TI - Association of Alcohol Consumption with Markers of Prostate Health and Reproductive Hormone Profiles: A Multi-Center Study of 4,535 Men in China. AB - BACKGROUND: The effect of alcohol consumption on prostate health and reproductive hormone profiles has long been investigated and currently, no consensus has been reached. Additionally, large studies focusing on this topic are relatively rare in China. PURPOSE: To investigate the association of alcohol consumption with prostate measurements and reproductive hormone profiles in Chinese population; and to examine the relationship between hormone levels and prostate measurements. METHODS: This cross-sectional study included 4535 men from four representative provinces of China. Demographic details, family history of prostate disease, tobacco and alcohol consumption, as well as International Prostate Symptom Score (I-PSS) were collected through a questionnaire. Total prostate specific antingen (total PSA), free PSA, free PSA/total PSA ratio (f/tPSA), and reproductive hormones were measured in serum. Multi-variable regression models were used to test for association of alcohol consumption with markers of prostate health, used to test for association of alcohol consumption with reproductive hormones, and reproductive hormones with markers of prostate health. RESULTS: Alcohol consumption had no obvious impact on total PSA concentration and I-PSS. Current drinkers had lower level of free PSA (beta = -0.11, p = 0.02) and f/tPSA (beta = 0.03, p = 0.005), former drinkers also had lower level of free PSA (beta = -0.19, p = 0.02) when compared with never drinkers. Lower Luteinizing hormone (LH) (beta = -1.05, p = 0.01), sex hormone-binding globulin (SHBG) (beta = -4.71, p = 0.01) and higher estradiol (beta = 7.81, p = 0.01) was found in current drinkers than never drinkers, whereas higher LH (beta = 1.04, p = 0.04) and free testosterone (FT) (beta = 0.03, p = 0.02) was detected in former drinkers than never drinkers. Furthermore, LH was positively associated with f/tPSA (beta = 0.002, p = 0.006), SHBG was also positively related with free PSA (beta = 0.003, p = 0.003) and f/tPSA (beta = 0.0004, p = 0.01). Both total testosterone (TT) and FT were inversely related with I-PSS (OR = 0.97, 95% CI, 0.95-0.98; OR = 0.23, 95% CI, 0.11-0.45, respectively). CONCLUSIONS: Alcohol consumption could affect serum free PSA concentration and also f/tPSA ratio, and also acts as an endocrine disruptor on the male reproductive hormone profiles. LH and SHBG were positively related with fPSA and f/tPSA, and higher level of TT and FT may be helpful for improving participants' subjective symptoms. PMID- 26559060 TI - First Record of Soft Tissue Preservation in the Upper Devonian of Poland. AB - Soft tissue preservation is reported from Upper Devonian deposits of the Holy Cross Mountains, central Poland, for the first time. The preserved soft tissues are muscles associated with arthropod cuticle fragments. The muscles are phosphatized with variable states of preservation. Well-preserved specimens display the typical banding of striated muscles. Other muscle fragments are highly degraded and/or recrystallized such that their microstructure is barely visible. The phosphatized muscles and associated cuticle are fragmented, occur in patches and some are scattered on the bedding plane. Due to the state of preservation and the lack of diagnostic features, the cuticle identification is problematic; however, it may have belonged to a phyllocarid crustacean. Taphonomic features of the remains indicate that they do not represent fossilized fecal matter (coprolite) but may represent a regurgitate, but the hypothesis is difficult to test. Most probably they represent the leftover remains after arthropod or fish scavenging. The present study shows that soft tissues, which even earlier were manipulated by scavenger, may be preserved if only special microenvironmental conditions within and around the animal remains are established. PMID- 26559061 TI - Morphological Analysis of Reticuloendothelial System in Capuchin Monkeys (Sapajus spp.) after Meso-2,3-Dimercaptosuccinic Acid (DMSA) Coated Magnetic Nanoparticles Administration. AB - Magnetic nanoparticles can be used for numerous in vitro and in vivo applications. However, since uptake by the reticuloendothelial system represents an obstacle for the achievement of nanoparticle diagnostic and therapeutic goals, the aim of the present study was to evaluate the uptake of dimercaptosuccinic acid coated magnetic nanoparticles by reticuloendothelial system phagocytic cells present in lymph nodes, spleen, and liver tissue and how the presence of these particles could have an impact on the morphology of these organs in capuchin monkeys (Sapajus spp.). Animals were intravenously injected with dimercaptosuccinic acid coated magnetic nanoparticles and euthanized 12 hours and 90 days post-injection. Organs were processed by transmission electron microscopy and histological techniques. Samples of spleen and lymph nodes showed no morphological changes. Nevertheless, liver samples collected 90 days post administration showed slight morphological alteration in space of Disse. Moreover, morphometrical analysis of hepatic mitochondria was performed, suggesting a clear positive correlation between mitochondrial area and dimercaptosuccinic acid coated magnetic nanoparticles administration time. The present results are directly relevant to current safety considerations in clinical diagnostic and therapeutic uses of magnetic nanoparticles. PMID- 26559062 TI - Benthic Trophic Interactions in an Antarctic Shallow Water Ecosystem Affected by Recent Glacier Retreat. AB - The western Antarctic Peninsula is experiencing strong environmental changes as a consequence of ongoing regional warming. Glaciers in the area are retreating rapidly and increased sediment-laden meltwater runoff threatens the benthic biodiversity at shallow depths. We identified three sites with a distinct glacier retreat related history and different levels of glacial influence in the inner part of Potter Cove (King George Island, South Shetland Islands), a fjord-like embayment impacted since the 1950s by a tidewater glacier retreat. We compared the soft sediment meio- and macrofauna isotopic niche widths (delta13C and delta15N stable isotope analysis) at the three sites to investigate possible glacier retreat-related influences on benthic trophic interactions. The isotopic niches were locally shaped by the different degrees of glacier retreat-related disturbance within the Cove. Wider isotopic niche widths were found at the site that has become ice-free most recently, and narrower niches at the older ice-free sites. At an intermediate state of glacier retreat-related disturbance (e.g. via ice-growler scouring) species with different strategies could settle. The site at the earliest stage of post-retreat development was characterized by an assemblage with lower trophic redundancy. Generally, the isotopic niche widths increased with increasing size spectra of organisms within the community, excepting the youngest assemblage, where the pioneer colonizer meiofauna size class displayed the highest isotopic niche width. Meiofauna at all sites generally occupied positions in the isotopic space that suggested a detrital-pool food source and/or the presence of predatory taxa. In general ice scour and glacial impact appeared to play a two-fold role within the Cove: i) either stimulating trophic diversity by allowing continuous re-colonization of meiofaunal species or, ii) over time driving the benthic assemblages into a more compact trophic structure with increased connectedness and resource recycling. PMID- 26559063 TI - Early effects of vertebroplasty or kyphoplasty versus conservative treatment of vertebral compression fractures in elderly polytrauma patients. AB - OBJECTIVE: This study aims to assess the early effects of operatively and nonoperatively managed vertebral compression fractures (VCFs) in elderly polytrauma patients. METHODS: A multi-center retrospective cohort study of operative treatment [vertebroplasty (VP) or kyphoplasty (KP)] versus nonoperative treatment (bed rest). RESULTS: A total of 40 patients received operative treatment and 59 patients received nonoperative treatment. The mean length of hospital stay was 15.53 +/- 6.994 days in the operative and 19.54 +/- 12.012 days in the nonoperative group (P = 0.039). The incidence of complication was higher in the nonoperative group than the operative group (P = 0.009), especially the incidence of bed rest complication (P = 0.024). Mortality rate was not significant difference between two groups (P = 0.172). CONCLUSIONS: For VCFs in elderly polytrauma patients, VP or KP can reduce length of hospital stay and complications, especially bed rest complication compared with nonoperative treatment. PMID- 26559064 TI - Acute kidney injury after heart transplant in young children: risk factors and outcomes. AB - BACKGROUND: Critical illness following heart transplantation can include acute kidney injury (AKI). Study objectives were to define the epidemiology of, risk factors for, or impact on outcomes of AKI after pediatric heart transplant. METHODS: Using data from a prospective study of 66 young children, we evaluated: (1) post-operative AKI rate (by pediatric modified RIFLE criteria); (2) pre, intra, and early post-operative AKI risk factors using stepwise logistic regression (3) effect of AKI on short-term outcomes (ventilation and length of pediatric intensive care unit (PICU) stay) using stepwise multiple regression. RESULTS: AKI occurred in 73 % of children. Pre-transplant ventilation and higher baseline estimated creatinine clearance (eCCl) were independent risk factors for AKI. Pre-operative inotrope use was associated with reduced risk of AKI. Tacrolimus level emerged as important in multivariable risk prediction. Children with AKI had a longer duration of ventilation and length of pediatric intensive care unit (PICU) stay, with AKI being an independent predictor. CONCLUSIONS: AKI was common after heart transplant and associated with more complicated early post transplant course. Lower baseline eCCl was associated with lower incidence of AKI; this merits further investigation. The association of pre-operative inotropes with less AKI may reflect a pathophysiological mechanism or be a surrogate for clinical factors and management prior to transplant. Avoiding high tacrolimus levels may be a modifiable risk factor for AKI. PMID- 26559065 TI - Effect of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the expression of EphA2 in osteoblasts and osteoclasts. AB - Porphyromonas gingivalis (Pg) as the major pathogenic bacterium of chronic periodontitis can cause alveolar bone resorption. Lipopolysaccharide (LPS) is its main virulence factor. The Eph family plays an important role in maintaining bone homeostasis. In this study, the effects of P. gingivalis lipopolysaccharide (Pg LPS) on the expression of EphA2 in osteoblasts and osteoclasts were investigated. MC3T3-E1 cells and RAW264.7 cells were separately cultured in osteoblast conditioned medium and osteoclast-conditioned medium to induce their differentiation into osteoblasts and osteoclasts, respectively. MC3T3-E1 cells were treated with 1 MUg/mL of Pg-LPS 3, 7, and 14 d later, while RAW264.7 cells were treated with 10 MUg/mL of Pg-LPS 1, 3, and 5 d later. The results have shown that Pg-LPS increased the expression of EphA2 both in osteoblasts and osteoclasts, decreased the expression of osteogenic-related genes (ALP, Sp7), and increased the expression of osteoclast-related genes (MMP9, c-fos, ACP5, CtsK, and NFATc1). Tartrate-resistant acid phosphatase (TRAP) staining illustrated that Pg-LPS promoted osteoclast differentiation and decreased the activity of alkaline phosphatase. Therefore, analysis indicates that, when treated with Pg-LPS, the expression of EphA2 is upregulated while the activity of osteoblasts and osteoclasts was reduced and increased, respectively. Our data suggest that EphA2 is closely related to the formation of osteoblasts and resorption of osteoclast and is likely to play an role in bone resorption induced in chronic periodontitis. These findings may provide information on new targets for prevention and treatment of chronic periodontitis. PMID- 26559066 TI - In vitro production of cloned and transgenically cloned embryos from Guangxi Huanjiang Xiang pig. AB - Guangxi Huanjiang Xiang pig is a unique miniature pig strain that is originally from Huanjiang Maonan Autonomous County of Guangxi province, China, and shows great potential in agricultural and biomedical research. Although cloning and genetic modification of this pig would enhance its application value, cloning of this strain has not yet been reported. We sought to establish appropriate cloning procedures and produce transgenic embryos in Huanjiang Xiang pigs through the following methods. We isolated fibroblasts from tails of Huanjiang Xiang pig and genetically modified them using Xfect transfection. Fibroblasts, either in non transgenic or transgenic forms, were used as donor cells for reconstructed embryos by somatic cell nuclear transfer (SCNT), and in vitro development was monitored after the reconstruction. We found no difference in blastocyst formation rate between non-transgenic and transgenic embryos (10.8% vs. 10.3%; P >= 0.05). In addition, we tested whether Scriptaid, a widely used histone deacetylase inhibitor, could enhance the in vitro development of Huanjiang Xiang pig cloned embryos. Treatment with 500 nM Scriptaid for 16 h post-activation significantly increased the blastocyst formation rate (26.1% vs. 10.8% for non transgenic nuclear transfer groups with vs. without the Scriptaid treatment and 28.5% vs. 10.3% for transgenic nuclear transfer groups with vs. without the Scriptaid treatment; P < 0.05). This study provided a basis for further generation of cloned and transgenically cloned Huanjiang Xiang pigs used in agricultural and biomedical research. PMID- 26559067 TI - Augmentation of oxidative stress-induced apoptosis in MCF7 cells by ascorbate tamoxifen and/or ascorbate-juglone treatments. AB - Since reactive oxygen species (ROS) play diverse roles in cancer, modulating the redox status of cancerous cells seems to be a promising therapeutic approach. Oxidant-targeted therapy appears logical for intervention with the acquired adaptive response to oxidative stress in cancer. In this study, we investigated the cytotoxic effects of juglone (J) and tamoxifen (T) and also the combination of each with ascorbate (A): tamoxifen/ascorbate (TA) and/or juglone/ascorbate (JA) on MCF7 cancerous cells. The results revealed that the growth inhibitory effects of juglone and tamoxifen were each associated with enhanced levels of ROS production and lipid peroxidation. These effects were markedly intensified in tamoxifen/ascorbate and juglone/ascorbate co-treatments. On the other hand, the intracellular anti-oxidant components such as reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and glutathione peroxidase significantly declined in cells subjected to combination treatments compared to that in cells exposed solely to tamoxifen, juglone, and the untreated control cells. In addition, ascorbate association induced more apoptotic and necrotic or necrotic like cell death than cells treated with each drug alone. These results were further confirmed by comparing the Bax/Bcl2 ratio in combination-treated cells. Additionally, ascorbate was able to potentiate the cytotoxic effects of combination therapy via activation of ROS-responsive factors including Foxo family members. PMID- 26559069 TI - Edoxaban for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. AB - INTRODUCTION: Oral anticoagulation is central to the management of patients with atrial fibrillation (AF) and at least one additional stroke risk factor. For decades, the vitamin K antagonists (e.g. warfarin) remained the only oral anticoagulant available for stroke prevention in AF. The non-vitamin K oral anticoagulants (NOACs) are now available, and these drugs include the direct thrombin inhibitors and factor Xa inhibitors. The latter class includes edoxaban, which has recently been approved for stroke prevention in AF by the United States Food and Drug Administration and the European Medicine Agency. In line with other NOACs, edoxaban avoids the many limitations of warfarin associated with variability of anticoagulation effect and multiple food and drug interactions. AREAS COVERED: In this review, the currently available evidence on edoxaban in patients with non-valvular AF is discussed. The pharmacology, efficacy and safety, and current aspects of use of edoxaban in patients with non-valvular AF for stroke and thromboembolism prevention are reviewed. EXPERT OPINION: Phase III trials on edoxaban for stroke prevention in non-valvular AF confirms non inferiority of edoxaban compared to well-managed warfarin both in terms of efficacy and safety. Currently ongoing and future trials as well as real-world data are warranted to confirm its effectiveness and safety for chronic anticoagulation and improve evidence in other areas which are lacking evidence where NOAC use remains controversial. PMID- 26559068 TI - Generation of cleidocranial dysplasia-specific human induced pluripotent stem cells in completely serum-, feeder-, and integration-free culture. AB - Human pluripotent stem cells hold great promise for their practical and scientific potentials. To improve understanding of self-renewal and differentiation, we previously reported a defined serum-free medium hESF9 could generate and maintain human induced pluripotent stem cells (iPSCs) in serum- and feeder-free culture conditions using retroviral vectors. To avoid the unpredictable side effects associated with retrovirus integration, we report here the successful generation of hiPSCs from dental pulp cells with a non-integrating replication-defective and persistent Sendai virus (SeVdp) vector expressing four key reprogramming genes. We found that hESF9 medium in combination with fibronectin are effective for generating and maintaining hiPSCs with SeVdp (KOSM). Using this system, pluripotent and self-renewing hiPSCs could be easily and stably generated and propagated. With this system, we successfully generated hiPSCs from cleidocranial dysplasia (CCD) caused by a heterozygous germ-line mutation of runt-related protein2 (RUNX2), which has an important role in the differentiation of osteoblasts and maturation of chondrocytes. This is the first report of the establishment of CCD-specific iPSCs. The cartilage in the teratomas of CCD-iPSCs showed abnormalities. These CCD-iPSCs would be beneficial to clarify the molecular mechanism and for development of medical applications. Moreover, it brings new pathophysiological role of RUNX2 in the differentiation of the human chondrocytes and osteocytes. PMID- 26559070 TI - An acute knee injury: tracking a two-year recovery online. AB - Current government policy aims to deliver high quality healthcare by recording accurate data at the point of giving care, storing it efficiently and displaying it in a format, which is easily interpreted by healthcare professionals and patients. Few published reports describe the benefits of collecting and reporting such data from the point of view of the patient. We report the case of a 62-year old lorry driver who used a web-based system to track patient reported outcome measures (PROMs) following an acute knee injury to full recovery over a 24-month period. The system reports clinical outcome scores in real-time to the patient and their medical team, clearly illustrating and enhancing recovery from injury. This case reveals how local software meets the needs of the individual patient linking and integrating such local systems must be the future focus of eHealth within the NHS to release the benefits presented by the information revolution. PMID- 26559071 TI - Role-based access control through on-demand classification of electronic health record. AB - Electronic health records (EHR) provides convenient method to exchange medical information of patients between different healthcare providers. Access control mechanism in healthcare services characterises authorising users to access EHR records. Role Based Access Control helps to restrict EHRs to users in a certain role. Significant works have been carried out for access control since last one decade but little emphasis has been given to on-demand role based access control. Presented work achieved access control through physical data isolation which is more robust and secure. We propose an algorithm in which selective combination of policies for each user of the EHR database has been defined. We extend well known data mining technique 'classification' to group EHRs with respect to the given role. Algorithm works by taking various roles as class and defined their features as a vector. Here, features are used as a Feature Vector for classification to describe user authority. PMID- 26559072 TI - Applying CHAID algorithm to investigate critical attributes of secured interoperable health data exchange. AB - With enhanced interoperability in healthcare environment the exchange of electronic health records (EHRs), both intra and inter organisations, has increased manifold. Sharing of the EHR creates room for illegal disclosures and confidentiality breaches. Interoperable healthcare is a complex system with many independent components. To design a secured framework for such a system, one need to understand the most important security attributes and predict various dependencies among them. The security attributes selected for statistical analysis are taken from the real-time study of patient-doctor relationship existing in any hospital or clinic. Hospitals with functional EHR-systems are the prerequisite of this study. The dependencies in the obtained data are generated through classification technique, chi-squared automatic interaction detection (CHAID). The decision tree obtained is analysed and verified using regression. The paper enabled the identification of the salient feature controlling which would maximally reduce security threats while sharing EHRs in interoperable healthcare environment. PMID- 26559073 TI - Exploring mobile health in a private online social network. AB - Health information is very vulnerable. Certain individuals or corporate organisations will continue to steal it similar to bank account data once data is on wireless channels. Once health information is part of a social network, corresponding privacy issues also surface. Insufficiently trained employees at hospitals that pay less attention to creating a privacy-aware culture will suffer loss when mobile devices containing health information are lost, stolen or sniffed. In this work, a social network system is explored as a m-health system from a privacy perspective. A model is developed within a framework of data driven privacy and implemented on Android operating system. In order to check feasibility of the proposed model, a prototype application is developed on Facebook for different services, including: i) sharing user location; ii) showing nearby friends; iii) calculating and sharing distance moved, and calories burned; iv) calculating, tracking and sharing user heart rate; etc. PMID- 26559074 TI - Macro influencers of electronic health records adoption. AB - While adoption rates for electronic health records (EHRs) have improved, the reasons for significant geographical differences in EHR adoption within the USA have remained unclear. To understand the reasons for these variations across states, we have compiled from secondary sources a profile of different states within the USA, based on macroeconomic and macro health-environment factors. Regression analyses were performed using these indicator factors on EHR adoption. The results showed that internet usage and literacy are significantly associated with certain measures of EHR adoption. Income level was not significantly associated with EHR adoption. Per capita patient days (a proxy for healthcare need intensity within a state) is negatively correlated with EHR adoption rate. Health insurance coverage is positively correlated with EHR adoption rate. Older physicians (>60 years) tend to adopt EHR systems less than their younger counterparts. These findings have policy implications on formulating regionally focused incentive programs. PMID- 26559075 TI - Culture, Development and Self: The Work of Robert A. LeVine. PMID- 26559076 TI - 1H, 15N and 13C chemical shift assignment of the Gram-positive conjugative transfer protein TraHpIP501. AB - Conjugative transfer of DNA represents the most important transmission pathway in terms of antibiotic resistance and virulence gene dissemination among bacteria. TraH is a putative transfer protein of the type IV secretion system (T4SS) encoded by the Gram-positive (G+) conjugative plasmid pIP501. This molecular machine involves a multi-protein core complex spanning the bacterial envelope thereby serving as a macromolecular secretion channel. Here, we report the near complete (1)H, (13)C and (15)N resonance assignment of a soluble TraH variant comprising the C-terminal domain. PMID- 26559077 TI - Direct calculation of anisotropic surface stresses during deformation of a particle-covered drop. AB - The modification of the surface tension and the surface shear elasticity by particles in particle-covered drops can be attributed to a particle-induced surface stress. This stress represents at the macroscopic, continuum level the microscopic effect of lateral particle-particle interactions. Understanding the link between the isotropic and anisotropic components of the surface stress and the particle microstructure, and how these components change when structured interfaces deform, is a crucial problem in the field of particle-laden interfaces. In this paper, we analyse static and transient three-dimensional simulations of a pendant drop whose surface is covered by colloidal particles displaying purely repulsive particle-particle interactions. We compute the isotropic and anisotropic surface stress from the inter-particle forces using a version of the Kirkwood-Irving formula suitable for interfacial suspensions; we validate the approach by comparing against surface tension values obtained using Fordham's method (Proc. R. Soc. London, Ser. A, 1948, 194). In the parameter range simulated, the combination of parameters for which the drop does not pinch off (stable drop) gives rise to a homogeneous and isotropic surface stress; we argue that in the absence of attractive interactions the drop becomes unstable before anisotropic effects can manifest themselves. For unstable drops, stress non-uniformity and anisotropy are significant when the drop deformation and the solid area fraction are sufficiently large. Our results have implications for the dynamic deformation of structured interfaces with geometrically complex and time dependent morphologies. PMID- 26559078 TI - Broadening the differential diagnosis in extracranial giant cell arteritis. PMID- 26559080 TI - Chronic psychosis, delayed diagnosis and Wilson's disease. PMID- 26559079 TI - Inhaled treatment for chronic obstructive pulmonary disease: what's new and how does it fit? AB - Since chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction, inhaled bronchodilators form the mainstay of treatment. A variety of new inhaled drugs and inhaler devices have recently been licensed and approved for prescribing to patients with COPD; many such drugs have been formulated in devices to deliver two different drugs at the same time. The evidence based review article highlights all of the drugs now licensed, describes some of the evidence surrounding their use and highlights practical steps in helping decide when these drugs should be considered in the context of guidelines. PMID- 26559082 TI - Severe cutaneous vasculitis: an unusual complication of equine antithymocyte globulin treatment. PMID- 26559081 TI - Expression of Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) predicts poor prognosis in lung adenocarcinoma and EGFR-mutated adenocarcinoma patients. AB - BACKGROUND: Sodium-potassium-chloride cotransporter isoform 1 (NKCC1) is an active ions cotransporter and modulates cellular volume and migration. NKCC1 blockers can inhibit cancer cell growth. AIM: We aimed to elucidate the expression and prognostic significance of NKCC1 in non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 788 NSCLC patients with either adenocarcinoma (n = 503) or squamous cell carcinoma (n = 285) by immunohistochemistry to correlate NKCC1 expression with clinicopathologic and survival outcomes. RESULTS: In adenocarcinoma, high NKCC1 expression was associated with larger tumor size (P = 0.013), vascular invasion (P < 0.001), lymphatic invasion (P < 0.001), perineural invasion (P = 0.019) and advanced pathologic stage (P < 0.001), but there are no significant correlations between NKCC1 expression and clinicopathological parameters in squamous cell carcinoma. Patients with high NKCC1 expression had significantly shorter disease-free survival (DFS;P < 0.001) and shorter overall survival (OS;P < 0.001) than those with low NKCC1 expression in adenocarcinoma. In squamous cell carcinoma, NKCC1 expression was not associated with prognosis. Multivariate analysis revealed that high NKCC1 expression was an independent prognostic factor for DFS in lung adenocarcinomas (HR, 1.709; 95% CI 1.029-2.130;P = 0.033) and for OS inEGFR mutated adenocarcinoma patients (HR, 3.165; 95% CI 1.424-7.035;P = 0.005). CONCLUSION: NKCC1 high expression predicted a bad clinical outcome for lung adenocarcinoma patients andEGFR-mutated subgroup. Therefore, NKCC1 may play a role in lung adenocarcinoma and novel therapeutic tactics could be developed by targeting NKCC1 protein. PMID- 26559083 TI - Tracheo-carotid artery fistula: an unusual cause of tracheostomy bleeding. PMID- 26559084 TI - Pharmacologic management of neuropsychiatric lupus. AB - Neuropsychiatric lupus affects above 50% of patients with systemic lupus erythematosus and may span from mild symptoms to acute devastating life threatening ones. Owing to the clinical variability, most pharmacological data rely on small, uncontrolled trials and case reports. The mainstay of therapy relies on immune-suppression by glucocorticoids, in adjunction with cyclophosphamide or anti-B-cell therapy, in moderate to severe cases. In selected scenarios (e.g., chorea) intravenous immunoglobulin or plasmapheresis may be effective. Anticoagulation is warranted if anti-phospholipid antibodies are present. In parallel there may be a need for symptomatic treatment such as anti epileptic or anti-depressive treatments, etc. In the future, more studies addressed to assess pathogenesis and preferred treatments of specific manifestations are needed in order to personalize treatments. PMID- 26559085 TI - Revalidation built on appraisal may have led to confusion. PMID- 26559086 TI - Once-daily luliconazole cream 1% for the treatment of interdigital tinea pedis. AB - Luliconazole is an imidazole antifungal agent with a unique chemical structure. In this article, we summarize the in vitro data, animal studies and clinical trial data relating to the use of topical luliconazole cream 1% in the treatment of tinea pedis. Preclinical studies have demonstrated potent activity against dermatophytes. Luliconazole has strong fungicidal activity against Trichophyton spp., similar to that seen with terbinafine. Evidence from clinical trials in tinea pedis have shown once-daily application of luliconazole cream 1% for 14 days to be effective and well tolerated. PMID- 26559087 TI - Glioblastoma Multiforme: The Genetic Perspective of the Treatment Planning. AB - Glioblastoma multiforme (GBM) is divided into two distinct disease entities called primary and secondary GBM. The genetic and the epigenetic background of these tumors are highly variable. These tumors are not successfully treated because of their cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcomes of these tumors promote researchers to find new markers associated with prognosis and treatment planning. A better understanding of stem-like cells and the genetic and the epigenetic background of GBM are necessary for designing new effective treatments and developing novel molecular strategies to target tumor cells and glioblastoma stem cells. In this review, we discuss the new therapeutic targets. Focusing on inhibiting the signaling pathways, which are associated with hypoxia-mediated maintenance of glioblastoma stem cells or the knockdown of the hypoxia-inducible factor 1-alpha (HIF1alpha), may help to the develop new target-specific treatments. PMID- 26559088 TI - Ligands and Regulatory Modes of Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma) in Avians. AB - Nutrient and gene interaction is an important aspect of poultry metabolism that determines performance capacity. New technological tools in biochemistry and biotechnology make it possible to explore the molecular base of phenotypic characteristics of poultry production. Fats act as energy deposits in the poultry body and are an essential constituent of animal cell membranes. From a functional standpoint, it has been suggested that ingested lipids change liver fatty acid synthesis and other lipogenic enzymes by regulating mRNA synthesis. Nuclear hormone receptors are ligand-activated transcription factors that control several genes involved in lipid metabolism. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of transcription factors. Three separate PPAR genes have been identified; they are known as alpha, delta, and gamma. The most important metabolic effect of PPARgamma in chicken is its task in adipogenesis. Reviewing the ligands of chicken PPARgamma gene can be useful to a better understanding of PPARgamma regulatory functions. PMID- 26559089 TI - MicroRNA-34 Family and Its Role in Cardiovascular Disease. AB - MicroRNAs (miRNAs) have been considered important regulators in both physiological and disease contexts. Among all miRNAs, the miR-34 family (miR-34a, -34b, -34c), which has been well characterized as a tumor suppressor, displays diverse functions in noncancerous diseases. MiR-34 levels are relatively low in the cardiovascular system, but recently they have been reported to function in cardiovascular disorders by regulating apoptosis, telomere attrition, DNA damage, and inflammatory response. In this review, we mainly summarize their roles in cardiac senescence and ischemic diseases. PMID- 26559090 TI - Advances in Molecular Biomarkers for Gastric Cancer. AB - Gastric cancer (GC) is the second most frequent oncological cause of death, the fifth most common malignancy in the world, and accounts for 6.8% of all tumors. As an aggressive disease, GC is often diagnosed at an advanced stage, which is why it is a major cause of cancer-related death. In the last several decades, the incidence of GC has decreased, which should be credited to advances in diagnostic and therapeutic technologies including tumor-marker detection systems, imaging modalities, pathological methods, gastroscopy, and particularly surgical and pharmacologic interventions. Because they are economical, convenient, and noninvasive, the detection of conventional serum tumor biomarkers (e.g., CEA, CA19-9, and CA72-4) has been widely employed in the diagnosis and evaluation of GC. However, due to their poor specificity and sensitivity, these molecular markers cannot meet the demand of early GC detection. Hence, new and reliable tumor biomarkers are desperately needed. This review systematically summarizes the three most commonly used biomarkers of GC (e.g., CEA, CA19-9, and CA72-4) and addresses two categories of potential molecular biomarkers for the diagnosis of GC: microRNA and methylated DNA. PMID- 26559091 TI - Cell Competition: Roles and Importance as a Central Phenomenon. AB - Cell competition is a type of short-range cell-cell interaction first observed in Drosophila melanogaster. In two heterogeneous cell populations, cells that have a higher fitness level would have a competitive advantage and grow at the cost of neighbor cells that have comparatively lower fitness. This interaction is due to differences in expression levels of a specific protein in the two cell populations, and it is known as cell competition. In this review, we have studied recent findings of cell competition in different biological processes in Drosophila as well as mammalian systems. The purpose of this review is to collate important studies of competitive cell interactions, and to understand its roles and importance as a central phenomenon. This review provides evidence of the relevance of cell competition in various physiological and pathological conditions, such as size control in organ development, stem cell maintenance, tissue repair, organ regeneration, aging, formation of memory, and cancer. PMID- 26559092 TI - Implications of Mycobacterium Major Facilitator Superfamily for Novel Measures against Tuberculosis. AB - Major facilitator superfamily (MFS) is an important secondary membrane transport protein superfamily conserved from prokaryotes to eukaryotes. The MFS proteins are widespread among bacteria and are responsible for the transfer of substrates. Pathogenic Mycobacterium MFS transporters, their distribution, function, phylogeny, and predicted crystal structures were studied to better understand the function of MFS and to discover specific inhibitors of MFS for better tuberculosis control. PMID- 26559093 TI - Improving the Reprogramming Efficiency of Somatic Cells to Induced Pluripotent Stem Cells. AB - Reprogramming shifts somatic cells toward a pluripotent state, resulting in cells that are capable of producing any tissue type, which provides a unique system for regenerative medicine. However, the poor efficiency of this process has prevented the use of induced pluripotent stem cells (iPSCs) in clinical application of stem cell biology. Importantly, more recent work has highlighted novel reprogramming factors and new strategies to enhance the reprogramming process. In this review, we focus on the transition of somatic cells to iPSCs, effective routes to improve the reprogramming efficacy, and the potential mechanism underlying this process. PMID- 26559094 TI - TGF-beta in Inflammatory Bowel Diseases: A Tale of the Janus-Like Cytokine. AB - Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine that controls an immense number of cellular responses and plays a prominent role in maintaining homeostasis of most human organs. In the intestine, the TGF-beta is involved in mucosal defense, immune tolerance, inhibition of acute inflammation, promoting the wound-healing process, and suppressing tumor initiation. However, TGF-beta exhibits Janus-like features under certain physiologic conditions and chronic inflammation (e.g., inflammatory bowel diseases [IBDs]). Excessive TGF beta in IBDs favors chronic inflammation, incurs pathologic remolding, and facilitates the progression of colitis-associated inflammation (CAC). Considering the increasingly crucial roles of TGF-Beta in the development of IBDs, we overview its pathways and multifaceted effects at the steady-state and IBD conditions of the gut, respectively. In addition, we present potential therapeutic strategies aimed at restoring normal TGF-beta signaling in IBDs. PMID- 26559095 TI - The Epigenetic Modifications of Genes Associated with Tuberculosis Susceptibility and Implications for Epi-Drugs. AB - Epigenetics of genes associated with tuberculosis susceptibility such as DNA methylation, posttranslational histone modifications, and non-coding RNA remain largely untapped field for better tuberculosis control. Many genes involved in tuberculosis susceptibility (e.g., NRAMP1 (SLC11A1), IFNG, NOS2A, VDR, ISG15, TACO, TLR1, TLR, IL18R1, chemokines, PADI, DUSP14, MBL, and MASP-2) have been subjected to epigenetic modification. Our summary of these modifications provides fresh insights into the pathogenesis of tuberculosis and inspires targets discovery for host-derived therapy. PMID- 26559096 TI - Hypoxia Is the Driving Force Behind GBM and Could Be a New Tool in GBM Treatment. AB - Glioblastoma (GBM) can be divided into two distinct disease entities according to the genetic and the epigenetic background of the tumor. Tumor location is associated with high variability in its genetic abnormalities. The treatment procedures for these tumors are often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcomes of these tumors have encouraged researchers to find new markers associated with prognosis and treatment planning. In the present communication, we discuss hypoxia as a new therapeutic target of glioblastoma multiforme and the molecular and phenotypic effects of hypoxia on cancer cells. We focus on the inhibition of the signaling pathways, which is associated with the hypoxia-mediated maintenance of glioblastoma stem cells and the knockdown of the hypoxia-inducible factor 1-alpha (HIFlalpha). This discussion may contribute to the development of new specifically targeted treatments. Furthermore, we highlight the idea that hypoxia-inducible factors (HIFs) could be attractive molecular targets for GBM therapeutics. PMID- 26559098 TI - Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. AB - BACKGROUND: Limited observational evidence suggests potential benefit for subfertile women undergoing operative hysteroscopy with several anti-adhesion therapies (e.g. insertion of an intrauterine device (IUD) or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) to decrease intrauterine adhesions (IUAs). OBJECTIVES: To assess the effectiveness of anti adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. SEARCH METHODS: We searched the following databases from inception to March 2015: the Cochrane Menstrual Disorders and Subfertility Specialised Register, the Cochrane Central Register of Controlled Trials (2015, Issue 2), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched The Journal of Minimally Invasive Gynecology, and we contacted experts in the field. SELECTION CRITERIA: Randomised comparisons of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth or ongoing pregnancy. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second look, along with their mean adhesion scores or severity. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) method. MAIN RESULTS: We included 11 randomised studies on use of an inserted device versus no treatment (two studies; 84 women) or another inserted device (one study; 162 women), hormonal treatment versus no treatment or placebo (two studies; 131 women), gel versus no treatment (five studies; 383 women) and graft versus no graft (one study; 43 women). The total number of women randomly assigned was 924, but data on only 803 participants were available for analysis. The proportion of subfertile women varied from 0% (one study; 41 women), to less than 50% (six studies; 487 women), to 100% (one study; 43 women); the proportion was unknown in three studies (232 women). Most studies (9/11) were at high risk of bias with respect to one or more methodological criteria.We found no evidence of differences between anti-adhesion therapy and no treatment or placebo with respect to live birth rates (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.46 to 2.13, P value = 0.98, three studies, 150 women; low-quality evidence) and no statistical heterogeneity (Chi(2) = 0.14, df = 2 (P value = 0.93), I(2) = 0%).Anti-adhesion therapy was associated with fewer IUAs at any second-look hysteroscopy when compared with no treatment or placebo (OR 0.36, 95% CI 0.20 to 0.64, P value = 0.0005, seven studies, 528 women; very low-quality evidence). We found no statistical heterogeneity (Chi(2) = 2.65, df = 5 (P value = 0.75), I(2) = 0%). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 6 to 20).No evidence suggested differences between an IUD and an intrauterine balloon with respect to IUAs at second-look hysteroscopy (OR 1.23, 95% CI 0.64 to 2.37, P value = 0.54, one study, 162 women; very low-quality evidence). AUTHORS' CONCLUSIONS: Implications for clinical practiceThe quality of the evidence retrieved was low or very low for all outcomes. Clinical effectiveness of anti adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchAdditional studies are needed to assess the effectiveness of different anti-adhesion therapies for improving reproductive outcomes in subfertile women treated by operative hysteroscopy. PMID- 26559097 TI - In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles. AB - Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs. PMID- 26559099 TI - Fair and equal treatment. PMID- 26559100 TI - The clinician's role as patient educator. PMID- 26559101 TI - Introducing a buddying scheme for first year pre-registration students. AB - Student buddying schemes have been found to be helpful for a variety of different university students. This article describes a scheme where first year pre registration child nursing students are buddied with second-year students, which was first initiated in the academic year 2012/2013. The first year students were aware that peer support was available but contact was only maintained by a minority of students. At present it is uncertain what impact the scheme has had on attrition figures, particularly in the first year. Initial evaluation indicates that students found the scheme helpful and would like it to continue to be available to first-year students. PMID- 26559102 TI - Preceptors' views on their role in supporting newly qualified nurses. AB - BACKGROUND: Retention, stress and difficult transition are issues associated with new graduates entering the workforce. International literature has suggested there is a problem and preceptorship models have been introduced to assist new registrants. It is recognised that new registrants require support from a preceptor, however, the literature appears to focus attention on the preceptee's views, rather than the preceptor's. RESEARCH QUESTION: How do preceptors perceive their role in supporting newly qualified nurses/midwives? AIM: The aim of this article is to review the literature pertaining to preceptorship and explore the perceptions held by preceptors in relation to their role supporting newly qualified registrants. METHOD: A qualitative exploratory study was conducted using a purposive sample. Interviews were used to capture the data. FINDINGS AND DISCUSSION: The data analysis identified that overall preceptors do feel prepared for their role, however, they highlighted the benefits of preceptor updates and regular support. Preceptors identified rewards and challenges associated with this role. CONCLUSIONS: The first 6 months of being a registrant has challenges for both the preceptee and the preceptor. The implementation of preceptorship models that include preparation and support for preceptors is essential to alleviate issues of transition, retention and stress. Preceptors identified areas for improvement such as regular update sessions, formal peer support, and protected time to discuss and complete the documentation. PMID- 26559103 TI - Heart failure care for patients who do not speak English. AB - Heart failure affects 1-2% of the UK population with prevalence rates predicted to rise over the next decade. Ineffective education for patients with heart failure can lead to a failure to adhere to guidance, reduced self-care and increased hospital readmissions. The National Institute for Health and Care Excellence (NICE) and the World Health Organization (WHO) have issued clear guidelines on patient-centred care in heart failure, particularly in relation to patients' cultural and linguistic needs. Patients with heart failure should have access to an interpreter or advocate if needed. Furthermore, heart failure educational materials should be tailored to suit the individual and be accessible to people who do not speak or read English. This article explores the practice recommendations for these patients with heart failure and provides an overview of current guidelines associated with optimal patient outcomes. It also includes practical advice on translation services, and information and educational materials available for patients with heart failure who do not speak English. PMID- 26559104 TI - Meeting the unmet support needs of BME men with prostate cancer. AB - Men with prostate cancer from black and minority ethnic (BME) communities have reported many unmet information and support needs. A literature review identified the many challenges health professionals face in addressing these unmet needs, and suggested that not enough is known about the psychosocial effects of a prostate cancer diagnosis on men from BME communities in the UK. Affected men may have little or no awareness or knowledge of prostate cancer, receive inadequate information and fear the disease. Nurses can address these issues through improving patients' knowledge and awareness of prostate cancer, providing high quality information to patients and their families, alleviating fear and promoting survivorship among this minority group; they can also facilitate staff training. Health professionals should look beyond the physical effects and consider the psychosocial effects of such a diagnosis when assessing the needs of these men. Practitioners need to overcome the various challenges to meeting these needs to provide more effective care to men from BME groups. PMID- 26559105 TI - Quality of life in intensive care survivors. PMID- 26559106 TI - Ethnic differences in diabetes prevalence and ICT use. AB - BACKGROUND: Uptake of information and communication technology (ICT) by individuals with diabetes can assist nursing care delivery, and improve patient outcomes. However, it is unclear how such uptake relates to ethnic differences in diabetes risk. AIM: To assess the moderating effects of ICT uptake on South Asian excess diabetes prevalence over a specific elapsed timeframe, accounting for selected environmental, socio-economic, and behavioural risk factors. METHOD: Archived data from a UK Office for National Statistics household survey 2006-2011 (120 621 partly non-orthogonal participant records) were analysed using hierarchical binary logistic regression analyses. RESULTS: ICT uptake qualified ethnic differences in diabetes prevalence. Non-smoking diabetes cases living in terraced housing with a home computer were more likely to be South Asian than Caucasian. By contrast, such cases were more likely to be Caucasian if a computer was unavailable (OR: 0.61; CI: 0.43-0.86; P=0.005). Furthermore, diabetes cases from low-income, mobile-dependent homes were probably South Asian (OR: 0.05; CI: 0.00-0.50; P=0.012). CONCLUSIONS: Home computing was linked to better tobacco control among South Asians with diabetes living in terraced properties. Mobile phone dependence was pronounced in those that received income support. Implications for nursing care are considered. PMID- 26559107 TI - COPD: should we go for GOLD? PMID- 26559108 TI - Street triage for mental health crises. PMID- 26559109 TI - Learning disability community nursing team. PMID- 26559110 TI - BJN Award Runner-Up. PMID- 26559111 TI - BJN Award Runner-Up. PMID- 26559112 TI - Writing for publication: from staff nurse to nurse consultant. PMID- 26559113 TI - Reaffirming the need for good communication. AB - Michelle Gracia wasn't looking forward to her placement in a mental health hospital. Yet it turned out to be one of her most fulfilling, not least for what it taught her about communication. PMID- 26559114 TI - New language controls for European nurses and midwives. AB - Emeritus professor Alan Glasper, of the University of Southampton, discusses the new initiative by the Nursing and Midwifery Council (NMC) to ensure that all registrants have a sufficient grasp of the English language to fulfil the requirements of the Code. PMID- 26559115 TI - Health and adult social care in England: patient safety failings. AB - John Tingle discusses the Care Quality Commission's recent analysis of health and social care in England as it relates to the safety of acute NHS hospitals. PMID- 26559116 TI - Setting our sights on a Pathway to practice improvement. PMID- 26559117 TI - Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies. AB - Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbalpha and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbalpha numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbalpha- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID- 26559118 TI - Public policies and health systems in Sahelian Africa: theoretical context and empirical specificity. AB - This research on user fee removal in three African countries is located at the interface of public policy analysis and health systems research. Public policy analysis has gradually become a vast and multifaceted area of research consisting of a number of perspectives. But the context of public policies in Sahelian Africa has some specific characteristics. They are largely shaped by international institutions and development agencies, on the basis of very common 'one-size-fits-all' models; the practical norms that govern the actual behaviour of employees are far removed from official norms; public goods and services are co-delivered by a string of different actors and institutions, with little coordination between them; the State is widely regarded by the majority of citizens as untrustworthy. In such a context, setting up and implementing health user fee exemptions in Burkina Faso, Mali and Niger was beset by major problems, lack of coherence and bottlenecks that affect public policy-making and implementation in these countries. PMID- 26559120 TI - Infrared spectroscopic and chemometric approach for identifying binding medium in Sukias mansion's wall paintings. AB - This paper addresses the application of infrared spectroscopy in combination with chemometrics to identify wall painting's binding medium while employing pattern recognition techniques to process FTIR data-set of complex samples. In this regard, based on the historical documents and previous researches, firstly 56 standard samples were prepared to represent strata of Persian wall paintings in the Safavid period in addition to real historic samples from the case study; Sukias mansion. Then, each sample was analysed by the means of FTIR and chemometrics. Finally, SIMCA was applied to the whole region of studied IR spectra which predicted egg yolk as the binding medium of Sukias mansion samples. PMID- 26559119 TI - Reactions of electrophiles with nucleophilic thiolate sites: relevance to pathophysiological mechanisms and remediation. AB - Electrophiles are electron-deficient species that form covalent bonds with electron-rich nucleophiles. In biological systems, reversible electrophile nucleophile interactions mediate basal cytophysiological functions (e.g. enzyme regulation through S-nitrosylation), whereas irreversible electrophilic adduction of cellular macromolecules is involved in pathogenic processes that underlie many disease and injury states. The nucleophiles most often targeted by electrophiles are side chains on protein amino acids (e.g. Cys, His, and Lys) and aromatic nitrogen sites on DNA bases (e.g. guanine N7). The sulfhydryl thiol (RSH) side chain of cysteine residues is a weak nucleophile that can be ionized in specific conditions to a more reactive nucleophilic thiolate (RS(-)). This review will focus on electrophile interactions with cysteine thiolates and the pathophysiological consequences that result from irreversible electrophile modification of this anionic sulfur. According to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson, electrophiles and nucleophiles can be classified as either soft or hard depending on their relative polarizability. HSAB theory suggests that electrophiles will preferentially and more rapidly form covalent adducts with nucleophiles of comparable softness or hardness. Application of HSAB principles, in conjunction with in vitro and proteomic studies, have indicated that soft electrophiles of broad chemical classes selectively form covalent Michael-type adducts with soft, highly reactive cysteine thiolate nucleophiles. Therefore, these electrophiles exhibit a common mechanism of cytotoxicity. As we will discuss, this level of detailed mechanistic understanding is a necessary prerequisite for the rational development of effective prevention and treatment strategies for electrophile-based pathogenic states. PMID- 26559121 TI - Expert Opinion: International Task Force Criteria for the Clinical Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy. PMID- 26559122 TI - Predicting future trends in the burden of pertussis in the 21st century: implications for infant pertussis and the success of maternal immunization. AB - Support is growing for maternal immunization using acellular pertussis (aP) vaccines to prevent severe pertussis disease and deaths among very young, unvaccinated infants. Vaccine effectiveness of maternal immunization is 91% in preventing laboratory-confirmed pertussis in infants aged <3 months. To date, most mothers were primed in childhood with whole-cell pertussis vaccines. Soon, the generation of aP-primed individuals will become the new mothers-to-be. The shorter duration of protection afforded by aP vaccines, which is more pronounced with repeated aP boosters, may lead to increased pertussis circulation among aP primed parents. Maternal Tdap immunization in aP-primed mothers-to-be may become less effective. Additional measures to protect young infants may eventually be needed, along with new vaccines that induce higher quality and more durable responses. PMID- 26559123 TI - Probing the dynamics of highly excited toluene on the fs timescale. AB - Investigation of the dynamics of toluene-h8 (C6H5CH3), toluene-d8 (C6D5CD3) and toluene-alpha,alpha,alpha-d3 (C6H5CD3) has been performed utilizing the VUV pump IR probe technique on the fs timescale. Using the 5th harmonic (~160 nm) of a Ti:sapphire laser as the pump beam, two superimposed electronic states, the valence S3 and the Rydberg 4p, were excited by one-photon absorption, followed by ionization and dissociation induced by the probe beam (800 nm). Analysis of the transient signal of the parent (P(+)) and fragment ions ([P-H](+) or [P-D](+)) implies the existence of two different relaxation processes: (i) from the Rydberg and (ii) from the S3 valence state. Using a rate equation model, the decay times have been determined and comparison between the different isotopologues has been made. Conclusions on the relaxation path, the relative displacements of the potential energy surfaces and the activation energies needed have been drawn from the decay times. The signals corresponding to the fragment ions present a small in amplitude, but nonetheless, unambiguous periodical modulation, which is attributed to out-of-plane bending oscillation, involving also the methyl group. The dynamics of the H- and D-loss channels has been investigated. Especially for the case of toluene-alpha,alpha,alpha-d3, where both channels are in operation, it was found that the ratio of the abundance of H/D-loss dissociation reactions decreases as the pump-probe delay time increases. PMID- 26559124 TI - Antidote for Factor Xa Anticoagulants. PMID- 26559125 TI - Pharmacologic Characterization of AMG 334, a Potent and Selective Human Monoclonal Antibody against the Calcitonin Gene-Related Peptide Receptor. AB - Therapeutic agents that block the calcitonin gene-related peptide (CGRP) signaling pathway are a highly anticipated and promising new drug class for migraine therapy, especially after reports that small-molecule CGRP-receptor antagonists are efficacious for both acute migraine treatment and migraine prevention. Using XenoMouse technology, we successfully generated AMG 334, a fully human monoclonal antibody against the CGRP receptor. Here we show that AMG 334 competes with [(125)I]-CGRP binding to the human CGRP receptor, with a Ki of 0.02 nM. AMG 334 fully inhibited CGRP-stimulated cAMP production with an IC50 of 2.3 nM in cell-based functional assays (human CGRP receptor) and was 5000-fold more selective for the CGRP receptor than other human calcitonin family receptors, including adrenomedullin, calcitonin, and amylin receptors. The potency of AMG 334 at the cynomolgus monkey (cyno) CGRP receptor was similar to that at the human receptor, with an IC50 of 5.7 nM, but its potency at dog, rabbit, and rat receptors was significantly reduced (>5000-fold). Therefore, in vivo target coverage of AMG 334 was assessed in cynos using the capsaicin-induced increase in dermal blood flow model. AMG 334 dose-dependently prevented capsaicin induced increases in dermal blood flow on days 2 and 4 postdosing. These results indicate AMG 334 is a potent, selective, full antagonist of the CGRP receptor and show in vivo dose-dependent target coverage in cynos. AMG 334 is currently in clinical development for the prevention of migraine. PMID- 26559126 TI - Angiotensin II-Induced Hypertension Is Attenuated by Reduction of Sympathetic Output in NO-Sensitive Guanylyl Cyclase 1 Knockout Mice. AB - In the regulation of vascular tone, the dilatory nitric oxide (NO)/cGMP pathway balances vasoconstriction induced by the renin-angiotensin and sympathetic nervous systems. NO-induced cGMP formation is catalyzed by two guanylyl cyclases (GC), NO-sensitive guanylyl cyclase 1 (NO-GC1) and NO-GC2, with indistinguishable enzymatic properties. In vascular smooth muscle cells, NO-GC1 is the major isoform and is responsible for more than 90% of cGMP formation. Despite reduced vasorelaxation, NO-GC1-deficient mice are not hypertensive. Here, the role of NO GC1 in hypertension provoked by contractile agonists angiotensin II (Ang II) and norepinephrine (NE) was evaluated in NO-GC1-deficient mice. Hypertension induced by chronic Ang II treatment did not differ between wild-type (WT) and NO-GC1 knockout mice (KO). Also, attenuation of NO-dependent aortic relaxation induced by the Ang II treatment was similar in both genotypes and was most probably attributable to an increase of phosphodiesterase 1 expression. Analysis of plasma NE content-known to be influenced by Ang II-revealed lower NE in the NO-GC1 KO under Ang II-treated- and nontreated conditions. The finding indicates reduced sympathetic output and is underlined by the lower heart rate in the NO-GC1 KO. To find out whether the lack of higher blood pressure in the NO-GC1 KO is a result of reduced sympathetic activity counterbalancing the reduced vascular relaxation, mice were challenged with chronic NE application. As the resulting blood pressure was higher in the NO-GC1 KO than in WT, we conclude that the reduced sympathetic activity in the NO-GC1 KO prevents hypertension and postulate a possible sympatho excitatory action of NO-GC1 counteracting NO-GC1's dilatory effect in the vasculature. PMID- 26559127 TI - Trouble in Paradise: Unmeasured Confounding in Registry-based Studies of Etiologic Factors. PMID- 26559128 TI - Partial USH2A deletions contribute to Usher syndrome in Denmark. PMID- 26559129 TI - Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. PMID- 26559130 TI - Onset-related subtypes of Parkinson's disease differ in the patterns of striatal dopaminergic dysfunction: A positron emission tomography study. AB - PURPOSE: The young-onset subtype of Parkinson's disease (YOPD) differs from the late-onset subtype (LOPD) in drug responsiveness, incidence of motor complications, and prognosis. The pathophysiology underlying these differences remains largely unknown. This study investigated whether the two subtypes differ in the pattern of dysfunction in striatal (caudate and putamen) dopaminergic system and if the dopamine transporter (DAT) imaging patterns are associated with the clinical features of corresponding PD subtype. METHODS: We assessed the spatial pattern of striatal dopaminergic dysfunction in 40 YOPD and 47 LOPD with early to mid-stage PD with DAT imaging by positron emission tomography. Two sub regional parameters (caudate/putamen ratio and asymmetry index) were calculated to measure the spatial pattern of striatal dopaminergic dysfunction. RESULTS: The caudate/anterior putamen ratios were significantly higher in YOPD than that in the LOPD (P = 0.03 contralateral to the most affected side of the body and P = 0.004 ipsilateral), which was supported by significantly inverse correlations between age of onset and caudate/anterior putamen ratios (r = -0.428, P < 0.001 for the contralateral and r = -0.576, P < 0.001 for the ipsilateral). Sub regional DAT binding in caudate ipsilateral to affected limbs was significantly correlated with age, while DAT bindings in putamen were significantly inversely correlated with disease duration and UPDRS motor scores. CONCLUSION: The YOPD subtype suffers from an uneven pattern of dopaminergic dysfunction: more sparing of the caudate compared with the putamen, while the LOPD patients is with a relatively uniform pattern. PMID- 26559132 TI - Magnetite nanoparticles facilitate methane production from ethanol via acting as electron acceptors. AB - Potential for interspecies hydrogen transfer within paddy soil enrichments obtained via addition of magnetite nanoparticles and ethanol (named as PEM) was investigated. To do this, PEM derived from rice field of Hangzhou (named as PEM HZ) was employed, because it offered the best methane production performance. Methane production and Fe (III) reduction proceeded in parallel in the presence of magnetite. Inhibition experiments with 2-bromoethane sulfonate (BES) or phosphate showed that interspecies hydrogen transfer and Fe (III) reduction also occurred in methane production from ethanol. 16S rRNA-based Illumina sequencing results showed that Dechloromonas, Thauera, Desulfovibrio and Clostridium were the dominant putative Fe (III) -reducers, and that hydrogenotrophic Methanobacterium accounted for about 88% of the total archaeal community. These results indicated that magnetite nanoparticles that acted as electron acceptor could facilitate rapid oxidation of ethanol by members of the Fe (III) -reducers in PEM-HZ and establishment of the syntrophic relationship of Fe (III) -reducers with Methanobacterium via interspecies hydrogen transfer. Our results could offer a model to understand the microbial interaction with magnetite from a novel angle during methanogenesis. PMID- 26559131 TI - Intervention fidelity in a school-based diet and physical activity intervention in the UK: Active for Life Year 5. AB - BACKGROUND: Active for Life Year 5 (AFLY5) is an educational programme for Year 5 children (aged 9-10) designed to increase children's physical activity, decrease sedentary behaviour and increase fruit and vegetable intake. This paper reports findings from a process evaluation embedded within a randomised controlled trial evaluating the programme's effectiveness. It considers the fidelity of implementation of AFLY5 with a focus on three research questions: 1. To what extent was the intervention delivered as planned? 2. In what ways, if any, did the teachers amend the programme? and 3. What were the reasons for any amendments? METHODS: Mixed methods were used including data collection via observation of the intervention delivery, questionnaire, teacher's intervention delivery log and semi-structured interviews with teachers and parents. Qualitative data were analysed thematically and quantitative data were summarised using descriptive statistics. RESULTS: Following training, 42 of the 43 intervention school teachers/teaching staff (98%) were confident they could deliver the nutrition and physical activity lessons according to plan. The mean number of lessons taught was 12.3 (s.d. 3.7), equating to 77% of the intervention. Reach was high with 95% of children in intervention schools receiving lessons. A mean of 6.2 (s.d. 2.6) out of 10 homeworks were delivered. Median lesson preparation time was 10 min (IQR 10-20) and 28% of lessons were reported as having been amended. Qualitative findings revealed that those who amended the lessons did so to differentiate for student ability, update them for use with new technologies and to enhance teacher and student engagement. Teachers endorsed the aims of the intervention, but some were frustrated with having to adapt the lesson materials. Teachers also a reported tendency to delegate the physical activity lessons to other staff not trained in the intervention. CONCLUSIONS: Fidelity of intervention implementation was good but teachers' enthusiasm for the AFLY5 programme was mixed despite them believing that the messages behind the lessons were important. This may have meant that the intervention messages were not delivered as anticipated and explain why the intervention was found not to be effective. TRIAL REGISTRATION: ISRCTN50133740. PMID- 26559133 TI - Bt crops benefit natural enemies to control non-target pests. AB - Crops producing insecticidal crystal (Cry) proteins from Bacillus thuringiensis (Bt) control important lepidopteran pests. However, pests such as aphids not susceptible to Cry proteins may require other integrated pest management (IPM) tactics, including biological control. We fed aphids on Bt and non-Bt plants and analyzed the Bt protein residue in aphids and compared the effects of Bt plants and a pyrethroid, lambda-cyhalothrin, on the performance of three natural enemies (predators: Coleomegilla maculata and Eupeodes americanus; parasitoid Aphidius colemani) of the green peach aphid, Myzus persicae. No Bt protein residues in aphids were detected and no significant differences were recorded in the performance of pyrethroid-resistant aphids that fed on Bt broccoli expressing Cry1Ab or Cry1C, or on non-Bt broccoli plants treated or not treated with the pyrethroid. This indicated the aphids were not affected by the Cry proteins or the pyrethroid, thus removing any effect of prey quality. Tri-trophic experiments demonstrated that no C. maculata and E. americanus survived consumption of pyrethroid-treated aphids and that ovipositional behavior of A. colemani was impaired when provided with pyrethroid-treated aphids. In contrast, natural enemies were not affected when fed aphids reared on Bt broccoli, thus demonstrating the safety of these Bt plants for IPM. PMID- 26559134 TI - Demystifying Infant Mental Health: What the Primary Care Provider Needs to Know. AB - Infant mental health is an interdisciplinary professional field of inquiry, practice, and policy that is concerned with alleviating suffering and enhancing the social and emotional competence of young children. The focus of this field of practice is supporting the relationships between infants and toddlers and their primary caregivers to ensure healthy social and emotional development. Notably, the connection between early life experiences and lifelong health has been well established in the scientific literature. Without appropriate regulation from a supportive caregiver, exposure to extreme stressors in early childhood can result in wide-ranging physiological disruptions, including alterations to the developing brain and immune, metabolic, and cardiovascular systems. As part of this interdisciplinary team, pediatric primary care clinicians are in a unique position to incorporate infant mental health practice tenets during their frequent office visits with infants and toddlers. This article provides pediatric primary care clinicians with an overview of infant mental health practice and suggestions for the conscious promotion of positive early relationships as an integral component of well-child care. PMID- 26559135 TI - Missed Medical Appointments and Disease Control in Children With Type 1 Diabetes. AB - The need exists to identify children with type 1 diabetes who are at risk for poor outcomes, and we hypothesized that missed appointments could be a useful indicator. We aimed to describe the frequency of missed medical appointments in children with type 1 diabetes and evaluate the relationship between missed appointments and poor disease control. Medical records of 1,002 children aged 0 17 years with type 1 diabetes and two or more scheduled appointments during a 43 month period were reviewed. Sixty-eight percent of patients missed no appointments, 17% missed one appointment, and 15% missed two or more appointments. Compared with patients who missed no appointments, patients who missed two or more appointments were three times more likely to have a diabetic ketoacidosis episode and three times more likely to have a hemoglobin A1c level equal to or greater than 8.5%. They were also more likely to be a member of a racial/ethnic minority group and be publicly insured. Missed appointments may be an important indicator of poor treatment adherence, requiring targeted interventions. PMID- 26559136 TI - Parent Training Intervention to Manage Externalizing Behaviors in Children With Autism. AB - Children with autism spectrum disorder (ASD) are more likely than their typically developing peers to exhibit externalizing behaviors; however, the etiology in children with ASD may be different and related to the core deficits of the disorder. Although parent training interventions have been effective in decreasing externalizing behaviors in typically developing children, the effectiveness in children with ASD has not been established. An in-depth analysis of the child's behavior may provide the foundation upon which to develop an individualized parent training approach. This case study illustrates how a functional assessment interview was used to obtain in-depth information about externalizing behaviors exhibited by a child with ASD who is high functioning and how this information was used to develop an individualized parent training intervention. PMID- 26559137 TI - Discharge Facilitation: An Innovative PNP Role. AB - Efficient and safe transition from the hospital to the community setting remains a priority in health care. Providers face mounting pressure of both timely discharges and minimizing readmissions, because these factor have an impact on provider reimbursement. Traditionally in academic medical centers, rotating teams of resident physicians have been responsible for discharging inpatients. The acute care pediatric nurse practitioner (PNP), when discharging patients, may arrange follow-up care, prescribe medications, and sign discharge orders, as the resident physician does. Additionally, the PNP is positioned to provide continuity of care and provide detailed discharge teaching and care coordination. The goal of this article is to review the literature pertaining to the nurse practitioner role in discharge facilitation and describe the creation and impact of an innovative nurse practitioner discharge coordinator role at a large urban pediatric medical center where improved discharge times were achieved. PMID- 26559138 TI - Mortality and drug therapy in patients with chronic obstructive pulmonary disease: a network meta-analysis. AB - BACKGROUND: Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers. METHODS: A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA). The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted. RESULTS: The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09). Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models. Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included. These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients. CONCLUSION: Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality. Further research is warranted to strengthen this conclusion. PMID- 26559139 TI - Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial. AB - BACKGROUND: Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS). METHODS: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon beta-1a 44 MUg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed. RESULTS: Interferon beta-1a 44 MUg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume. CONCLUSIONS: These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon beta-1a 44 MUg SC tiw, rather than disease-related tissue loss. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01085318. PMID- 26559140 TI - Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis. AB - A major limitation for better understanding the role of the human gut virome in health and disease is the lack of validated methods that allow high throughput virome analysis. To overcome this, we evaluated the quantitative effect of homogenisation, centrifugation, filtration, chloroform treatment and random amplification on a mock-virome (containing nine highly diverse viruses) and a bacterial mock-community (containing four faecal bacterial species) using quantitative PCR and next-generation sequencing. This resulted in an optimised protocol that was able to recover all viruses present in the mock-virome and strongly alters the ratio of viral versus bacterial and 16S rRNA genetic material in favour of viruses (from 43.2% to 96.7% viral reads and from 47.6% to 0.19% bacterial reads). Furthermore, our study indicated that most of the currently used virome protocols, using small filter pores and/or stringent centrifugation conditions may have largely overlooked large viruses present in viromes. We propose NetoVIR (Novel enrichment technique of VIRomes), which allows for a fast, reproducible and high throughput sample preparation for viral metagenomics studies, introducing minimal bias. This procedure is optimised mainly for faecal samples, but with appropriate concentration steps can also be used for other sample types with lower initial viral loads. PMID- 26559141 TI - Acid-induced autophagy protects human lung cancer cells from apoptosis by activating ER stress. AB - An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly. In mouse tumors, the expression of cleaved caspase3 and p62 was enhanced by oral treatment with sodium bicarbonate, which can raise the intratumoral pH. Furthermore, the protein levels of ER stress markers, including p-PERK, p-eIF2alpha, CHOP, XBP-1s and GRP78, were also increased in response to acidic pH. The antioxidant NAC, which reduces ROS accumulation, alleviated acid-mediated ER stress and autophagy, and knocking down GRP78 reduced autophagy activation under acidic conditions, which suggests that autophagy was induced by acidic pH through ER stress. Taken together, these results indicate that the acidic microenvironment in non-small cell lung cancer cells promotes autophagy by increasing ROS-ER stress, which serves as a survival adaption in this setting. PMID- 26559143 TI - Research Domain Criteria (RDoC) and the DSM--Two Methodological Approaches to Mental Health Diagnosis. PMID- 26559142 TI - Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial. AB - BACKGROUND: The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. METHODS/DESIGN: The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. TRIAL REGISTRATION: The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 . PMID- 26559144 TI - Evaluation of a fitness intervention for new firefighters: injury reduction and economic benefits. AB - BACKGROUND: Firefighting is a hazardous profession and firefighters suffer workplace injury at a higher rate than most US workers. Decreased physical fitness is associated with injury in firefighters. A physical fitness intervention was implemented among Tucson Fire Department recruit firefighters with the goals of decreasing injury and compensation claims frequency and costs during the recruit academy, and over the subsequent probationary year. METHODS: Department injury records were analysed and described by body part, injury type and mechanism of injury. Injury and workers' compensation claims outcomes from the recruit academy initiation through the 12-month probationary period for the intervention recruit class were compared with controls from three historical classes. RESULTS: The majority of injuries were sprains and strains (65.4%), the most common mechanism of injury was acute overexertion (67.9%) and the lower extremity was the most commonly affected body region (61.7%). The intervention class experienced significantly fewer injuries overall and during the probationary year (p=0.009), filed fewer claims (p=0.028) and experienced claims cost savings of approximately US$33 000 (2013) from avoided injury and reduced claims costs. The estimated costs for programme implementation were $32 192 leading to a 1-year return on investment of 2.4%. CONCLUSIONS: We observed reductions in injury occurrence and compensation costs among Probationary Firefighter Fitness (PFF-Fit) programme participants compared with historical controls. The initiation of the PFF-Fit programme has demonstrated promise in reducing injury and claims costs; however, continued research is needed to better understand the programme's potential effectiveness with additional recruit classes and carryover effects into the recruit's career injury potential. PMID- 26559145 TI - Potential underestimation of pesticide suicide and its impact on secular trends in South Korea, 1991-2012. AB - BACKGROUND: Pesticide ingestion is among the most commonly used suicide methods globally. Underestimation of deaths by pesticide self-poisoning is thought to be common but under-researched. We investigated potential misclassification and underestimation of suicide by pesticide poisoning and their impact on trends in pesticide suicide in South Korea. METHODS: We compared sociodemographic profiles between deaths certified as suicide, undetermined deaths and injuries by poisoning using pesticides, unspecified chemicals and medicines/alcohol in South Korea (1991-2012), and calculated similarity scores. Joinpoint regression analysis was used to examine time trends. RESULTS: The profiles of deaths classified as pesticide suicides showed generally similar patterns to those for undetermined deaths/injuries by poisoning using pesticides and suicides/undetermined deaths/injuries by poisoning using unspecified chemicals. Over the study period, the number of pesticide suicides (on average 2033 per year; range 623-3530) would increase by 15%, 23% and 31%, when assuming that 20%, 30% and 40% of deaths in alternative cause-of-death categories were misclassified pesticide suicides respectively. Age-standardised rates of pesticide suicide increased more than four times in 1991-2003 but fell by around 50% in 2003-2012. This trend did not change when the assumed proportion of misclassification was 20%, whereas the rapid increase in 2000-2003 would be lessened if misclassification occurred by 30% or more. CONCLUSIONS: Pesticide suicides may be underestimated in South Korea as some are possibly misclassified as deaths due to other causes; however, such underestimation would not substantially affect estimated secular trends. PMID- 26559146 TI - Spencermartinsiella silvicola sp. nov., a yeast species isolated from rotting wood. AB - Three strains of a new xylanase-producing yeast species were isolated from rotting wood samples collected in the Atlantic Rain Forest of Brazil. The sequences of the internal transcribed spacer region and D1/D2 domains of the large subunit of the rRNA gene showed that this novel yeast species belongs to the genus Spencermartinsiella, and its closest relatives among recognized species are Spencermartinsiella europaea and Spencermartinsiella ligniputridi. A novel species, named Spencermartinsiella silvicola sp. nov., is proposed to accommodate these isolates. The type strain is UFMG-CM-Y274T ( = CBS 13490T). The MycoBank number is MB 813053. In addition, Candida cellulosicola is reassigned to the genus Spencermartinsiella as a new combination. PMID- 26559147 TI - Editorial overview: Endocrine and metabolic diseases: Waistline weapons: new therapeutic avenues for the treatment of obesity and metabolic disease. PMID- 26559148 TI - Public health challenges and legacies of Japan's response to the Ebola virus disease outbreak in West Africa 2014 to 2015. AB - The largest outbreak of Ebola virus disease occurred in West Africa in 2014 and resulted in unprecedented transmission even in distant countries. In Japan, only nine individuals were screened for Ebola and there was no confirmed case. However, the government promoted the reinforcement of response measures and interagency collaboration, with training and simulation exercises conducted country-wide. The legacies included: publication of a communication policy on case disclosure, a protocol for collaboration between public health and other agencies, and establishing an expert committee to assemble the limited available expertise. There were challenges in taking proportionate and flexible measures in the management of people identified to be at high risk at entry points to Japan, in the decentralised medical response strategy, and in the medical countermeasures preparedness. The Ebola outbreak in West Africa provided a crucial opportunity to reveal the challenges and improve the preparedness for rare but high impact emerging diseases that are prone to be neglected. Efforts to uphold the lessons learnt and maintain public health preparedness should help prepare for future emerging diseases, including bioterrorist acts and pandemics. PMID- 26559149 TI - Selectivity of flesh-footed shearwaters for plastic colour: Evidence for differential provisioning in adults and fledglings. AB - The ingestion of plastic by seabirds has been used as an indicator of population and ocean health. However, few studies have examined adults and juveniles of the same species concurrent with the availability of plastic in the local marine environment. In King George Sound (KGS), Western Australia, 13% of adult flesh footed shearwaters (Ardenna carneipes) and 90% of fledglings contained plastic items in their digestive tract. On Lord Howe Island (LHI), New South Wales, 75% of adult shearwaters and 100% of fledglings contained plastic. Ingested items were assessed using Jaccard's Index (where J = 0 indicates complete dissimilarity and J = 1 complete similarity). The colour of items ingested by self- and chick provisioning shearwaters from KGS exhibited broad overlap with plastic available in the local environment (J = 0.78-0.80), and plastic in adults and fledglings from LHI were less similar to those available (J = 0.31-0.58). Additional data on seabird colour selection would improve our understanding of the factors influencing the behaviour of ingesting plastic, and its contribution to the decline of some species. PMID- 26559150 TI - The behaviors of microplastics in the marine environment. AB - Despite the pollution of microplastics being internationally recognized, the understanding of their behaviors in marine environment is still developing. Microplastics are ubiquitous in the marine environment, with the potential to cause harm to marine ecosystem. Here, we would classify the behaviors of microplastics as physical behaviors (i.e. migration, sedimentation and accumulation), chemical behaviors (i.e. degradation and adsorption) and biobehaviors (i.e. ingestion, translocation and biodegradation), and a further discussion on their behavioral mechanisms were presented to better understand their impacts for the marine environment. PMID- 26559151 TI - Association Between MC-2 Peptide and Hepatic Perfusion and Liver Injury Following Resuscitated Hemorrhagic Shock. AB - IMPORTANCE: Hemorrhagic shock (HS) due to trauma remains a major cause of morbidity and mortality in the United States, despite continuing progression of advanced life support and treatment. Trauma is the third most common cause of death worldwide and is the leading cause of death in the 1- to 44-year-old age group. Hemorrhagic shock often progresses to multiple organ failure despite conventional resuscitation (CR) that restores central hemodynamics. OBJECTIVE: To examine whether MC-2 would bind glycosaminoglycans to decrease proinflammatory cytokines' influence in the liver, minimize organ edema, prevent liver injury, and improve hepatic perfusion. MC-2, a synthetic octapeptide derived from the heparin-binding domain of murine interferon gamma (IFN-gamma), binds glycosaminoglycans to modulate serum and interstitial cytokine levels and activity. DESIGN, SETTING, AND PARTICIPANTS: A controlled laboratory study of 3y male Sprague-Dawley rats that were randomized to 4 groups of 8 each: sham, sham+MC-2 (50 mg/kg), HS/CR, or HS/CR+MC-2 (HS = 40% of baseline mean arterial pressure for 60 minutes; CR = return of shed blood and 2 volumes of saline). The study began in March, 2013. MAIN OUTCOMES AND MEASURES: Effective hepatic blood flow (EHBF) by galactose clearance, wet-dry weights, cytokines, histopathology, complete metabolic panel, and complete blood cell count were performed at 4 hours after CR. RESULTS: MC-2 partially reversed the HS/CR-induced hepatic hypoperfusion at 3 and 4 hours postresuscitation compared with HS/CR alone. Effective hepatic blood flow decreased during the HS period from a mean (SD) of 7.4 (0.3) mL/min/100 g and 7.5 (0.5) mL/min/100g at baseline to 3.7 (0.4) mL/min/100g and 5.9 (0.5) mL/min/100g for the HS/CR and HS/CR+MC-2 groups, respectively (P <.05). Effective hepatic blood flow remained constant in the sham groups throughout the experimental protocol. Organ edema was increased in the ileum and liver in the HS/CR vs sham group, and MC-2 decreased edema in the ileum vs the HS/CR group. MC-2 in HS also decreased levels of alanine aminotransferase, zonula occludens-1, and interleukin-1beta compared with HS/CR alone. CONCLUSIONS AND RELEVANCE: MC-2 was associated with decreased liver injury, enhanced effective hepatic blood flow, decreased cytokines, and prevention of edema formation in the ileum when administered with CR following HS. These data suggest that the MC-2 peptide could be a potential therapeutic approach to target cytokine and chemokine interactions, which might limit multiple organ failure and decrease mortality in hemorrhagic shock. PMID- 26559152 TI - Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease. AB - Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR. PMID- 26559153 TI - miR-539 induces cell cycle arrest in nasopharyngeal carcinoma by targeting cyclin dependent kinase 4. AB - Dysregulation of microRNAs has been demonstrated to contribute to malignant progression of cancers, including nasopharyngeal carcinoma (NPC). miR-539 was previously reported to be significantly downregulated in osteosarcoma. However, the potential role and mechanism of action of miR-539 in the initiation and progression of NPC remain largely unknown. Quantitative reverse transcription (RT)-PCR demonstrated that miR-539 was significantly downregulated in NPC tumour tissues compared with nontumour tissues. The cell viability, colony formation assay and tumourigenicity assays in nude mice showed that miR-539 could inhibit NPC cell growth in vitro and in vivo. The cyclin-dependent kinase 4 (CDK4) was verified as a miR-539 target gene using dual-luciferase reporter assays, quantitative RT-PCR and Western blotting and was involved in miR-539-regulated NPC cell growth. These results indicated that miR-539 plays an important role in the initiation and progression of NPC by targeting CDK4 and the miR-539/CDK4 pathway may contribute to the development of novel therapeutic strategies for NPC in the future. PMID- 26559154 TI - The effect of fibreoptic bronchoscopy in acute respiratory distress syndrome: experimental evidence from a lung model. AB - Flexible bronchoscopy is essential for appropriate care during mechanical ventilation, but can significantly affect mechanical ventilation of the lungs, particularly for patients with acute respiratory distress syndrome. We aimed to describe the consequences of bronchoscopy during lung-protective ventilation in a bench study, and thereby to determine the optimal diameter of the bronchoscope for avoiding disruption of the protective-ventilation strategy during the procedure. Immediately following the insertion of the bronchoscope into the tracheal tube, either minute ventilation decreased significantly, or positive end expiratory pressure increased substantially, according to the setting of the inspiratory pressure limit. The increase in end-expiratory pressure led to an equivalent increase in the plateau pressure, and lung-protective ventilation was significantly altered during the procedure. We showed that a bronchoscope with an external diameter of 4 mm (or less) would allow safer bronchoscopic interventions in patients with severe acute respiratory distress syndrome. PMID- 26559155 TI - Establishing a process for conducting cross-jurisdictional record linkage in Australia. AB - OBJECTIVE: To describe the realities of conducting a cross-jurisdictional data linkage project involving state and Australian Government-based data collections to inform future national data linkage programs of work. METHODS: We outline the processes involved in conducting a Proof of Concept data linkage project including the implementation of national data integration principles, data custodian and ethical approval requirements, and establishment of data flows. RESULTS: The approval process involved nine approval and regulatory bodies and took more than two years. Data will be linked across 12 datasets involving three data linkage centres. A framework was established to allow data to flow between these centres while maintaining the separation principle that serves to protect the privacy of the individual. CONCLUSIONS: This will be the first project to link child immunisation records from an Australian Government dataset to other administrative health datasets for a population cohort covering 2 million births in two Australian states. IMPLICATIONS: Although the project experienced some delays, positive outcomes were realised, primarily the development of strong collaborations across key stakeholder groups including community engagement. We have identified several recommendations and enhancements to this now established framework to further streamline the process for data linkage studies involving Australian Government data. PMID- 26559156 TI - Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial. AB - The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio 3rd tertile vs. 1st tertile = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) 3rd tertile vs. 1st tertile = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR = 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk. PMID- 26559157 TI - How reader perception of capsule affects interpretation of washout in hypervascular liver nodules in patients at risk for hepatocellular carcinoma. AB - PURPOSE: To determine whether reader perception of a capsule affects reader interpretation of washout in hypervascular liver nodules at dynamic magnetic resonance imaging (MRI) in patients at risk for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study was Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA) compliant, with waiver of informed consent. MRI reports for 111 hypervascular liver nodules (median 2.0 cm, range 1.0-17.8 cm) in 62 patients were reviewed, and the presence/absence of capsule and washout were recorded for one reading. A second independent study reading was also performed. The signal intensity ratio (SIR) for each nodule and liver parenchyma was measured. An objective SIR threshold was identified for nodules without capsules that correctly classified the presence/absence of washout, then applied to nodules with capsules to classify them as having / not having objective washout. Nodules were categorized as definite / not definite HCC using subjective and objective washout, based on LI-RADS, OPTN, AASLD, and EASL criteria, and proportions compared using McNemar's test. RESULTS: Agreement on nodule features was high for Readings 1 and 2 (kappa = 0.70-0.82). For Reading 1, 71 nodules lacked capsules (43 with and 28 without subjective washout); an SIR threshold of 0.88 classified the presence/absence of washout correctly in 94% (67/71, P < 0.001). Forty nodules had capsules; although all had subjective washout (100%, 40/40), 75% (30/40) had objective washout (P < 0.05). Using objective washout caused 4.5% (3/66; LI-RADS, OPTN) and 12% (10/83; AASLD, EASL) of nodules to be recategorized from definite HCC to not definite HCC. CONCLUSION: Reader perception of capsule affects interpretation of washout. This effect can influence nodule categorization using imaging-based diagnostic systems. J. Magn. Reson. Imaging 2016;43:1337-1345. PMID- 26559158 TI - Thin Water Films at Multifaceted Hematite Particle Surfaces. AB - Mineral surfaces exposed to moist air stabilize nanometer- to micrometer-thick water films. This study resolves the nature of thin water film formation at multifaceted hematite (alpha-Fe2O3) nanoparticle surfaces with crystallographic faces resolved by selected area electron diffraction. Dynamic vapor adsorption (DVA) in the 0-19 Torr range at 298 K showed that these particles stabilize water films consisting of up to 4-5 monolayers. Modeling of these data predicts water loadings in terms of an "adsorption regime" (up to 16 H2O/nm(2)) involving direct water binding to hematite surface sites, and of a "condensation regime" (up to 34 H2O/nm(2)) involving water binding to hematite-bound water nanoclusters. Vibration spectroscopy identified the predominant hematite surface hydroxo groups (-OH, MU-OH, MU3-OH) through which first layer water molecules formed hydrogen bonds, as well as surface iron sites directly coordinating water molecules (i.e., as geminal eta-(OH2)2 sites). Chemometric analyses of the vibration spectra also revealed a strong correspondence in the response of hematite surface hydroxo groups to DVA-derived water loadings. These findings point to a near-saturation of the hydrogen-bonding environment of surface hydroxo groups at a partial water vapor pressure of ~8 Torr (~40% relative humidity). Classical molecular dynamics (MD) resolved the interfacial water structures and hydrogen bonding populations at five representative crystallographic faces expressed in these nanoparticles. Simulations of single oriented slabs underscored the individual roles of all (hydro)oxo groups in donating and accepting hydrogen bonds with first layer water in the "adsorption regime". These analyses pointed to the preponderance of hydrogen bond-donating -OH groups in the stabilization of thin water films. Contributions of MU-OH and MU3-OH groups are secondary, yet remain essential in the stabilization of thin water films. MD simulations also helped resolve crystallographic controls on water-water interactions occurring in the "condensation regime". Water-water hydrogen bond populations are greatest on the (001) face, and decrease in importance in the order (001) > (012) ~ (110) > (014) ? (100). Simulations of a single (~5 nm * ~ 6 nm * ~ 6 nm) nanometric hematite particle terminated by the (001), (110), (012), and (100) faces also highlighted the key roles that sites at particle edges play in interconnecting thin water films grown along contiguous crystallographic faces. Hydroxo-water hydrogen bond populations showed that edges were the preferential loci of binding. These simulations also suggested that equilibration times for water binding at edges were slower than on crystallographic faces. In this regard, edges, and by extension roughened surfaces, are expected to play commanding roles in the stabilization of thin water films. Thus, in focusing on the properties of nanometric-thick water layers at hematite surfaces, this study revealed the nature of interactions between water and multifaced particle surfaces. Our results pave the way for furthering our understanding of mineral-thin water film interfacial structure and reactivity on a broader range of materials. PMID- 26559159 TI - CE: Inside an Ebola Treatment Unit: A Nurse's Report. AB - In December 2013, the first cases of the most recent outbreak of Ebola virus disease (formerly known as Ebola hemorrhagic fever) emerged in the West African nation of Guinea. Within months the disease had spread to the neighboring countries of Liberia and Sierra Leone. The international humanitarian aid organization Medecins Sans Frontieres (MSF; known in English as Doctors Without Borders) soon responded by sending staff to set up treatment centers and outreach triage teams in all three countries. In August 2014, the World Health Organization declared the outbreak an international public health emergency.In September 2014, the author was sent by MSF to work as a nurse in an Ebola treatment unit in Liberia for five weeks. This article describes her experiences there. It provides some background, outlines the practices and teams involved, and aims to convey a sense of what it's like to work during an Ebola outbreak and to put a human face on this devastating epidemic. PMID- 26559160 TI - CE: Incorporating Acupressure into Nursing Practice. AB - Rooted in traditional Chinese medicine, the use of acupressure to alleviate symptoms, support the healing process, promote relaxation, and improve overall health has grown considerably in the West. The effects of acupressure--like those of acupuncture, with which it shares a theoretical framework--cannot always be explained in terms of Western anatomical and physiologic concepts, but this noninvasive practice involves minimal risk, can be easily integrated into nursing practice, and has been shown to be effective in treating nausea as well as low back, neck, labor, and menstrual pain. The author discusses potential clinical indications for the use of acupressure, describes the technique, explains how to evaluate patient outcomes, and suggests how future research into this integrative intervention might be improved. PMID- 26559161 TI - Time to first antibiotic and mortality in adults hospitalised with community acquired pneumonia: a matched-propensity analysis. AB - A matched-propensity analysis of national data from the British Thoracic Society community-acquired pneumonia audit was conducted (n=13 725). Overall, time to first antibiotic (TFA) was <=4 h in 63%. Adjusted 30-day inpatient (IP) mortality was lower for adults with TFA <=4 h compared with TFA >4 h (adjusted OR 0.84, 95% CI 0.74 to 0.94; p=0.003). Increasing TFA was associated with greater OR of 30 day IP mortality (p value for trend=0.001), but no TFA threshold was evident. Although we found an association between TFA and mortality, we cannot say whether this is causal or whether TFA might just be a quality measure for overall or other processes of care. PMID- 26559162 TI - Annual volume of very low-birth-weight infant deliveries appears to be more important than level of neonatal intensive care unit for optimising perinatal care. PMID- 26559163 TI - Observational studies are compatible with an association between saturated and trans fats and cardiovascular disease. PMID- 26559164 TI - Evaluation of the Synthetic Potential of an AHBA Knockout Mutant of the Rifamycin Producer Amycolatopsis mediterranei. AB - Supplementing an AHBA(-) mutant strain of Amycolatopsis mediterranei, the rifamycin producer, with a series of benzoic acid derivatives yielded new tetraketides containing different phenyl groups. These mutasynthetic studies revealed unique reductive properties of A. mediterranei towards nitro- and azidoarenes, leading to the corresponding anilines. In selected cases, the yields of mutaproducts (fermentation products isolated after feeding bacteria with chemically prepared analogs of natural building blocks) obtained are in a range (up to 118 mg L(-1)) that renders them useful as chiral building blocks for further synthetic endeavors. The configuration of the stereogenic centers at C6 and C7 was determined to be 6R,7S for one representative tetraketide. Importantly, processing beyond the tetraketide stage is not always blocked when the formation of the bicyclic naphthalene precursor cannot occur. This was proven by formation of a bromo undecaketide, an observation that has implications regarding the evolutionary development of rifamycin biosynthesis. PMID- 26559165 TI - Paternal-specific S-allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection. AB - Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post pollination, prezygotic sexual selection, with male-male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S haplotype frequencies. PMID- 26559166 TI - Utility of Continuous Metabolic Syndrome Score in Assessing Risk of Type 2 Diabetes: The Isfahan Diabetes Prevention Study. AB - BACKGROUND/AIM: It is not clear whether levels of continuous metabolic syndrome (cMetS) are associated with type 2 diabetes (T2D). The aim of this study was to determine the ability of the cMetS score to predict progression to T2D in non diabetic first-degree relatives (FDRs) of patients with T2D in Isfahan, Iran. METHODS: A total of 1,869 non-diabetic FDRs 30-70 years old in 2003-2005 were followed through 2014 for the occurrence of T2D. At baseline and through follow ups, participants underwent a standard 75 g 2-h oral glucose tolerance test. MetS was defined by the National Cholesterol Education Program-Adult Treatment Panel III. The cMetS score was calculated using age- and gender-standardized Z-score for MetS components. Receiver operating characteristic (ROC) curve was used to assess the association between cMetS and components of MetS with T2D. RESULTS: During 13,571 person-years of follow-up, 72 men and 210 women developed diabetes. Those in the top quartile of cMetS were 8.0 times more likely to develop diabetes than those in the bottom quartile (OR 7.96; 95% CI 4.88-12.99). On ROC curve analysis, a higher area under the ROC were found for FPG (74.3%; 95% CI 70.8 77.8), than for cMetS (69.4%; 95% CI 66.0-72.8). CONCLUSIONS: The cMetS score is a robust predictor of T2D and may be more effective and efficient than the current binary definition of MetS in predicting progression to T2D in our study population. PMID- 26559167 TI - Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III). AB - AIM: There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. METHOD: An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. RESULTS: The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6-monthly physical examination to annual anoscopy +/- biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old. CONCLUSION: Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s. PMID- 26559168 TI - Australasian specialist emergency medicine workforce: Here and now ... and beyond. PMID- 26559169 TI - Not all the number of skeletal muscle fibers is determined prenatally. AB - BACKGROUND: The investigation of skeletal muscle development is of importance in stock farming and biomedicine. It is still ambiguous that whether animals are born with the full set of skeletal muscle fibers or if the number of myofibers continues to increase postnatally. RESULTS: Here, an inducible lineage-tracing system was employed to monitor the changes of myofiber number in various skeletal muscles during development. We confirm that the total myofiber number of longissimus dorsi, gastrocnemius and rectus femoris is determined prenatally. However, tibialis anterior and extensor digitorum longus have a different development pattern, and their myofiber number still increases in the first postnatal week and then remains stable afterwards. CONCLUSIONS: Our results highlight different development time frames of anatomically distinct skeletal muscles. PMID- 26559170 TI - Barriers to the use of genetic information for the development of new epilepsy treatments. AB - Genetic analysis is providing new information on the biological basis of epilepsy at a rapid pace; this article identifies factors acting as major barriers to use of these data for therapy development. Disease heterogeneity is a primary obstacle since so many genes can cause or predispose to epilepsy and the clinical presentation of epilepsy is so diverse, thus making it difficult to define the most therapeutically relevant targets. Further, many epilepsy genes affect brain development, an observation that represents a barrier unto itself given the challenge of reversing or preventing genetically mediated alterations of brain pathway formation. Finally, the lack of appropriate models for testing new therapies is also recognized as a fundamental limitation. Overcoming these barriers will be aided by full characterization of the genetic landscape of epilepsy, elucidation of key pathway points for therapeutic intervention and creation of unique experimental models to validate results. PMID- 26559171 TI - Simple assembly of long nanowires through substrate stretching. AB - Although nanowire (NW) alignment has been previously investigated, minimizing limitations such as process complexity and NW breakage, as well as quantifying the quality of alignment, have not been sufficiently addressed. A simple, low cost, large-area, and versatile alignment method is reported that is applicable for NWs either grown on a substrate or synthesized in solution. Metal and semiconductor NWs with average lengths of up to 16 MUm are aligned through the stretching of polyvinyl alcohol (PVA) films, which compared to other stretching methods results in superior alignment because of the large stretching ratio of PVA. Poly[oxy(methyl-1,2-ethanediyl)] is employed as lubricant to prevent NW breakage. To quantify NW alignment, a simple and effective image processing method is presented. The alignment process results in an order parameter (S) of NW alignment as high as 0.97. PMID- 26559173 TI - Erratum: ECRJ Corrigendum. AB - [This corrects the article DOI: 10.3402/ecrj.v2.26634.]. PMID- 26559172 TI - The efficacy of dantrolene sodium for muscle cramps in patients with localized scleroderma. PMID- 26559174 TI - Detecting Arbitrary DNA Mutations Using Graphene Oxide and Ethidium Bromide. AB - We propose a simple and fast method for detecting arbitrary DNA mutations. Single stranded DNA probes labeled with fluorescein amidite (FAM-ssDNA), ethidium bromide (EB), and graphene oxide (GO) are employed in the sensing system. The detection is achieved in two steps. In the first step, the sensing system contains FAM-ssDNA probes and EB molecules. It exhibits different fluorescence emissions in the presence of perfectly matched, mismatched, and random DNA sequences. With the addition of GO in the second step, the fluorescence signal for perfectly matched and random DNA does not vary greatly, which, however, experiences a significant change for mismatched DNA targets. The signal ratio before and after the addition of GO can clearly distinguish mutations from normal and random DNA sequences. The detection method works well regardless of the mutation positions and only requires "mix-and-detect" steps, which are completed within 15 min. PMID- 26559175 TI - Gene mapping and functional analysis of the novel leaf color gene SiYGL1 in foxtail millet [Setaria italica (L.) P. Beauv]. AB - Setaria italica and its wild ancestor Setaria viridis are emerging as model systems for genetics and functional genomics research. However, few systematic gene mapping or functional analyses have been reported in these promising C4 models. We herein isolated the yellow-green leaf mutant (siygl1) in S. italica using forward genetics approaches. Map-based cloning revealed that SiYGL1, which is a recessive nuclear gene encoding a magnesium-chelatase D subunit (CHLD), is responsible for the mutant phenotype. A single Phe to Leu amino acid change occurring near the ATPase-conserved domain resulted in decreased chlorophyll (Chl) accumulation and modified chloroplast ultrastructure. However, the mutation enhanced the light-use efficiency of the siygl1 mutant, suggesting that the mutated CHLD protein does not completely lose its original activity, but instead, gains novel features. A transcriptional analysis of Chl a oxygenase revealed that there is a strong negative feedback control of Chl b biosynthesis in S. italica. The SiYGL1 mRNA was expressed in all examined tissues, with higher expression observed in the leaves. Comparison of gene expression profiles in wild-type and siygl1 mutant plants indicated that SiYGL1 regulates a subset of genes involved in photosynthesis (rbcL and LHCB1), thylakoid development (DEG2) and chloroplast signaling (SRP54CP). These results provide information regarding the mutant phenotype at the transcriptional level. This study demonstrated that the genetic material of a Setaria species could be ideal for gene discovery investigations using forward genetics approaches and may help to explain the molecular mechanisms associated with leaf color variation. PMID- 26559176 TI - Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism. AB - ESSENTIALS: When high probability of pulmonary embolism (PE), sensitivity of computed tomography (CT) is unclear. We investigated the sensitivity of multidetector CT among 134 patients with a high probability of PE. A normal CT alone may not safely exclude PE in patients with a high clinical pretest probability. In patients with no clear alternative diagnosis after CTPA, further testing should be strongly considered. BACKGROUND: Whether patients with a negative multidetector computed tomographic pulmonary angiography (CTPA) result and a high clinical pretest probability of pulmonary embolism (PE) should be further investigated is controversial. METHODS: This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria. Among patients with a negative CTPA result, the diagnosis of PE required at least one of the following conditions: ventilation/perfusion lung scan showing a high probability of PE in a patient with no history of PE, abnormal findings on venous ultrasonography in a patient without previous deep vein thrombosis at that site, or the occurrence of venous thromboembolism (VTE) in a 3-month follow-up period after anticoagulation was withheld because of a negative multidetector CTPA result. RESULTS: We identified 498 patients with a priori clinical assessment of a high probability of PE and a completed CTPA study. CTPA excluded PE in 134 patients; in these patients, the pooled incidence of VTE was 5.2% (seven of 134 patients; 95% confidence interval [CI] 1.5-9.0). Five patients had VTEs that were confirmed by an additional imaging test despite a negative CTPA result (five of 48 patients; 10.4%; 95% CI 1.8-19.1), and two patients had objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months (two of 86 patients; 2.3%; 95% CI 0-5.5). None of the patients had a fatal PE during follow-up. CONCLUSIONS: A normal multidetector CTPA result alone may not safely exclude PE in patients with a high clinical pretest probability. PMID- 26559177 TI - The vastus lateralis free flap for lower extremity gustilo grade III reconstruction. AB - BACKGROUND: Orthopedic trauma patients with Gustilo grade III injuries to the distal third of lower extremity present challenges to optimum reconstructive management. There is no consensus on the ideal autologous tissue for transfer in large lower extremity defect reconstruction. We present a large case series utilizing the vastus lateralis (VL) free flap for lower extremity Gustilo grade III reconstruction. PATIENTS AND METHODS: This is a case series of patients who underwent VL free tissue transfer for Gustilo grade III injuries. A total of 38 free tissue transfers were performed for lower extremity reconstruction, 19 of which were VL flaps. Mean interval between injury and reconstruction was 46 days (range 7-240 days). RESULTS: The mean wound size was 11.37 cm x 11.42 cm and all cases underwent delayed reconstruction. Seven day flap viability was 100% and 30 day flap viability was 17/19 (89%). There were six complications: two hematomas requiring drainage, one flap dehiscence, one distal flap loss requiring a reverse saphenous vein graft extension, and two complete flap losses. Of the two failed flaps, one was attributed to heparin-induced thrombocytopenia and the other to venous congestion complicated by methicillin-resistant Staphylococcus aureus infection. CONCLUSIONS: The VL free flap is a reliable and versatile flap that can be tailored and tangentially thinned to match the shape and size of a defect, and the long pedicle allows the surgeon to stay away from the zone of injury. This flap should be strongly considered for lower extremity reconstruction, especially in salvage operations for large defects. (c) 2015 Wiley Periodicals, Inc. Microsurgery 37:212-217, 2017. PMID- 26559178 TI - Photosensitizer-assembled PEGylated graphene-copper sulfide nanohybrids as a synergistic near-infrared phototherapeutic agent. AB - OBJECTIVES: Stimulative nanostructures play a crucial role in developing the smart nanomedicine for high therapeutic efficacy with minimum adverse effects. Herein, a near-infrared (NIR) light-responsive nanohybrids p-nanographene oxide (GO)-copper sulfide (CuS)/indocyanine green (ICG) comprised of GO, CuS nanoparticles and photosensitizer ICG was fabricated to couple the photothermal property of CuS and photodynamic effect of ICG in one system in order to achieve the synergistic phototherapy. METHODS: pGO-CuS/ICG was constructed by self assembling ICG on pGO-CuS nanostructure. Its physicochemical, photothermal and photodynamic properties were studied by spectroscopic methods. The in vitro cellular uptake, cytotoxicity, the single/combined photothermal therapeutic (PTT) and photodynamic therapeutic (PDT) effects were investigated with biological techniques. RESULTS: pGO-CuS/ICG exhibited high efficacy of photothermal conversation and singlet oxygen generation under NIR laser excitation. It entered into the target cancer cells probably via passive transmembrane pathway and exerted obvious PTT and PDT effect against the tumor cells upon irradiation with the respective 940 and 808 nm lasers. In particular, the tremendous synergistic efficacy of PDT and PTT had been demonstrated by tuning the NIR laser combined irradiation. CONCLUSIONS: This study promises the future applications of pGO CuS/ICG as a NIR light activable theranostic nanodrug for deep-seated cancer noninvasive phototherapy. PMID- 26559179 TI - Fluorescent Analogue of Batimastat Enables Imaging of alpha-Secretase in Living Cells. AB - The ADAM family of metalloproteases cleave a diverse range of transmembrane substrates, resulting in the release of their soluble ectodomains. This process of protein shedding, termed alpha-secretase processing, is involved in many facets of both normal and disease related cellular function. While the processing of substrates has been well documented, the regulation and trafficking of the ADAMs are less well understood. Tools that allow for the study of ADAMs under their native environment will allow for a better understanding of their regulation and activity. Here we describe the design and evaluation of a novel fluorescent analogue of a well-characterized ADAM inhibitor, Batimastat. This probe exhibited similar activity for inhibiting alpha-secretase processing in cells as did Batimastat. Importantly, this probe specifically labeled ADAMs fluorescently in both fixed and living cells, enabling the possibility to study the trafficking of alpha-secretase proteins in a dynamic environment. PMID- 26559180 TI - Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration. AB - Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects. PMID- 26559181 TI - Preparation of hybrid materials for controlled drug release. AB - Authors obtained hybrid organic-inorganic materials applied in sustained drug delivery. The materials are ibuprofen as a model drug, hydroxyapatite and three different polymers as supports. Influence of the type of employed polymer, an inorganic carrier, on the properties and drug release profiles was estimated. Flory-Huggins interaction parameters, the dispersive component of surface free energy and acid-base characteristic of the surface were used to assess the behavior of the composites in terms of drug release. The experiments were carried out with the use of inverse gas chromatography (IGC), Fourier transform infrared (FTIR) and ultraviolet (UV) techniques. FTIR and ATR-FTIR spectra were collected. The values of [Formula: see text] parameter obtained for all investigated materials (excluding poly(L-lactide) (PLA2)) indicate low or medium activity. The strongest interactions (the lowest values of the Flory-Huggins [Formula: see text] parameter) are observed for PLA2 composition, while the weakest interactions for systems with polyethylene glycol (PEG). Finally, drug release profiles are shown. For materials prepared with Eudragit(r) (EUD) and PLA, the release of drug was much smaller, which corresponds to lower values of Flory Huggins parameter. The executed experiments allowed the estimation of the properties of prepared composites. Prepared materials present properties required in sustained drug release and may be successfully applied as drug delivery systems. PMID- 26559182 TI - Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome. AB - Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide excision repair (NER) in clustered oxidative DNA adducts. To identify the in vivo protective roles of NER, we established a human cell line lacking the NER gene xeroderma pigmentosum group A (XPA). XPA knockout (KO) cells were generated from TSCER122 cells derived from the human lymphoblastoid TK6 cell line. To analyze the mutagenic events in DNA adducts in vivo, we previously employed a system of tracing DNA adducts in the targeted mutagenesis (TATAM), in which DNA adducts were site-specifically introduced into intron 4 of thymidine kinase genes. Using the TATAM system, one or two tandem 7,8-dihydro-8-oxoguanine (8-oxoG) adducts were introduced into the genomes of TSCER122 or XPA KO cells. In XPA KO cells, the proportion of mutants induced by a single 8-oxoG (7.6%) was comparable with that in TSCER122 cells (8.1%). In contrast, the lack of XPA significantly enhanced the mutant proportion of tandem 8-oxoG in the transcribed strand (12%) compared with that in TSCER122 cells (7.4%) but not in the non-transcribed strand (12% and 11% in XPA KO and TSCER122 cells, respectively). By sequencing the tandem 8-oxoG-integrated loci in the transcribed strand, we found that the proportion of tandem mutations was markedly increased in XPA KO cells. These results indicate that NER is involved in repairing clustered DNA adducts in the transcribed strand in vivo. PMID- 26559183 TI - Syngonanthus androgynus, a Striking New Species from South America, its Phylogenetic Placement and Implications for Evolution of Bisexuality in Eriocaulaceae. AB - In the present study, we describe and illustrate a remarkable new species of Syngonanthus from South America (Bolivia, Brazil and Peru). This new species is quickly distinguished from all species in the genus by trimerous and bisexual flowers, a unique set of characteristics in Syngonanthus. Complementary to this study, sequences of 33 species were downloaded from GenBank and four species had sequences newly generated for this study. Molecular phylogenetic analyses based on nuclear ribosomal ITS and the plastid regions psbA-trnH and trnL-F were performed to determine its systematic position. The results have shown S. androgynus closely related to a well-supported clade that has been treated as Syngonanthus sect. Carphocephalus. Floral traits associated with this new plant also were surveyed. Character reconstruction suggests that the bisexual flowers originated independently more than once in the genus. However, trimerous flowers appear to be an ancestral condition of the whole genus. PMID- 26559184 TI - A Cross-Sectional Survey of Healthcare Workers on the Knowledge and Attitudes towards Polio Vaccination in Pakistan. AB - INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan. METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results. RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42 +/- 2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75 +/- 5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio. CONCLUSION: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan. PMID- 26559185 TI - Accuracy of Blood Pressure-to-Height Ratio to Define Elevated Blood Pressure in Children and Adolescents: The CASPIAN-IV Study. AB - The aim of this study was to propose a simple practical diagnostic criterion for pre-hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group. This study was conducted on a nationally representative sample of 14,880 students, aged 6-18 years. HTN and pre-HTN were defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >= 95 and 90-95th percentile for age, gender, and height, respectively. By using the area under the curve (AUC) of the receiver operator characteristic curves, we estimated the diagnostic accuracy of two indexes of SBP-to-height ratio (SBPHR) and DBP-to-height (DBPHR) to define pre-HTN and HTN. Overall, SBPHR performed relatively well in classifying subjects to HTN (AUC 0.80-0.85) and pre-HTN (AUC 0.84-0.90). Likewise, DBPHR performed relatively well in classifying subjects to HTN (AUC 0.90-0.97) and pre-HTN (AUC 0.70-0.83). Two indexes of SBPHR and DBPHR are considered as valid, simple, inexpensive, and accurate tools to diagnose pre-HTN and HTN in pediatric age group. PMID- 26559186 TI - Isotopic Differences between Forage Consumed by a Large Herbivore in Open, Closed, and Coastal Habitats: New Evidence from a Boreal Study System. AB - Documenting habitat-related patterns in foraging behaviour at the individual level and over large temporal scales remains challenging for large herbivores. Stable isotope analysis could represent a valuable tool to quantify habitat related foraging behaviour at the scale of individuals and over large temporal scales in forest dwelling large herbivores living in coastal environments, because the carbon (delta13C) or nitrogen (delta15N) isotopic signatures of forage can differ between open and closed habitats or between terrestrial and littoral forage, respectively. Here, we examined if we could detect isotopic differences between the different assemblages of forage taxa consumed by white tailed deer that can be found in open, closed, supralittoral, and littoral habitats. We showed that delta13C of assemblages of forage taxa were 3.0 0/00 lower in closed than in open habitats, while delta15N were 2.0 0/00 and 7.4 0/00 higher in supralittoral and littoral habitats, respectively, than in terrestrial habitats. Stable isotope analysis may represent an additional technique for ecologists interested in quantifiying the consumption of terrestrial vs. marine autotrophs. Yet, given the relative isotopic proximity and the overlap between forage from open, closed, and supralittoral habitats, the next step would be to determine the potential to estimate their contribution to herbivore diet. PMID- 26559187 TI - Comments on "Local Anesthetic Systemic Toxicity". PMID- 26559188 TI - Response to "Comments on 'Local Anesthetic Systemic Toxicity'". PMID- 26559189 TI - A 1H NMR Investigation of the Interaction between Phenolic Acids Found in Mango (Manguifera indica cv Ataulfo) and Papaya (Carica papaya cv Maradol) and 1,1 diphenyl-2-picrylhydrazyl (DPPH) Free Radicals. AB - The benefits of phenolic acids on human health are very often ascribed to their potential to counteract free radicals to provide antioxidant protection. This potential has been attributed to their acidic chemical structure, which possesses hydroxyl groups in different positions. Phenolic acids can interact between themselves and exhibit an additive, antagonistic or synergistic effect. In this paper, we used 1H NMR to analyze the interactions and mechanisms that are present in major phenolic acids found in mango (gallic, protocatechuic, chlorogenic and vanillic acids) and papaya (caffeic, ferulic and p-coumaric acids), and the DPPH radical was used to evaluate the effect of the antioxidant mixtures. The interactions were found to occur via hydrogen bonds between the -OH and -COOH groups. Moreover, the phenolic acids exhibit two types of mechanisms for the neutralization of the DPPH radical. According to the results, these two mechanisms are Hydrogen Atom Transfer (HAT) and Single Electron Transfer (SET). The ability of the phenolic acid to neutralize the DPPH radical decreases in the following order in mango: gallic > chlorogenic > protocatechuic > vanillic. Moreover, within the acids found in papaya, the order was as follows: caffeic > p coumaric > ferulic. PMID- 26559190 TI - Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection. AB - Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease. PMID- 26559191 TI - Measuring and Validating a General Cancer Predisposition Perception Scale: An Adaptation of the Revised-IPQ-Genetic Predisposition Scale. AB - BACKGROUND: Illness perceptions are linked to individual help-seeking and preventive behaviors. Previous illness perception studies have identified five dimensions of illness-related experience and behaviour. The Revised Illness Perception Questionnaire (IPQ-R) for genetic predisposition (IPQ-R-GP) was developed to measure illness perceptions in those genetically-predisposed to blood disease. We adapted the IPQ-R-GP to measure perceptions of generalized cancer predisposition. This paper describes the development and validation of the Cancer Predisposition Perception Scale (CPPS). METHODS: The draft CPPS scale was first administered to 167 well Hepatitis B carriers and 123 other healthy individuals and the factor structure was examined using Exploratory Factor Analysis. Then the factor structure was confirmed in a second sample comprising 148 healthy controls, 150 smokers and 152 passive smokers using Confirmatory Factor Analysis (CFA). RESULTS: Six-factors comprising 26 items provided optimal fit by eigen and scree-plot methods, accounting for 58.9% of the total variance. CFA indicated good fit of the six-factor model after further excluding three items. The six factors, Emotional representation (5 items), Illness coherence (4 items), Treatment control (3 items), Consequences (5 items), Internal locus of control (2 items) and External locus of control (4 items) demonstrated adequate to-good subscale internal consistency (Cronbach's alpha = 0.63-0.90). Divergent validity was suggested by low correlations with optimism, self-efficacy, and scales for measuring physical and psychological health symptoms. CONCLUSION: The CPPS appears to be a valid measure of perceived predisposition to generic cancer risks and can be used to examine cancer-risk-related cognitions in individuals at higher and lower cancer risk. PMID- 26559192 TI - Fifth metacarpal neck fractures treated with soft wrap/buddy taping compared to reduction and casting: results of a prospective, multicenter, randomized trial. AB - INTRODUCTION: The majority of fifth metacarpal neck fractures (boxers fracture) are treated conservatively without surgery. The purpose of this prospective, randomized, multicenter trial was to determine if the outcomes of soft wrap and buddy taping (SW) was noninferior to reduction and cast (RC) in boxer's fracture with palmar angulation <=70 degrees and no rotational deformity. MATERIALS AND METHODS: Sixty-eight patients with similar characteristics were prospectively enrolled and randomized at four institutions. Our primary outcome was measured by the shortened Disabilities of the Arm, Shoulder and Hand (quickDASH) questionnaire at 4 months. Noninferiority was claimed if there was no more than +10 points difference in the quickDASH. Other secondary radiographic and clinical outcomes were measured. RESULTS: At 4 months, mean difference in the quickDASH between the two groups was -10.4 (95 % confidence interval, -27.0; +6.2) which was under the pre-specified margin. There was no significant difference between both groups' secondary outcomes of pain, satisfaction with the esthetic appearance, mobility of the metacarpophalangeal-joint at flexion and extension, or power grip. Increased fracture angulation, as measured on follow-up radiographs, was not significantly different between both groups. The degree of palmar fracture angulation was not related to work leave or profession. Duration of time off from work was 11 days shorter in SW compared to RC (P = 0.03). CONCLUSION: This study supports the use of soft wrap and buddy taping for treatment of boxer's fracture with palmar angulation <=70 degrees and no rotational deformity. Although there was no statistical difference in satisfaction with the esthetic appearance, the patient must be willing to accept the loss of the "knuckle" with this treatment method. PMID- 26559193 TI - Cognitive function in cancer survivors: analysis of the 1999-2002 National Health and Nutrition Examination Survey. AB - PURPOSE: Cancer and its treatment may affect cognitive function through a number of direct and indirect pathways including inflammation, lipid metabolism, vascular damage, and changes in the blood-brain barrier. While short-term treatment-related cognitive changes are well recognized, only limited research is available in older, long-term survivors of cancer. METHODS: Using NHANES data from 1999 to 2002, 408 cancer survivors and 2639 non-cancer participants aged 60 years old and above were identified. Cognitive function of these groups were compared using the Digit Symbol Substitution Test (DSST) and self-reported problems with memory or confusion. RESULTS: After adjustment for covariates, cancer survivors scored, on average, 1.99 points lower on the DSST compared to non-cancer survivors (-1.99, 95 % CI -3.94, -0.05). Cancer survivors also had 17 % higher odds of self-reporting problems with memory or confusion (OR 1.17, 95 % CI 0.89, 1.53). CONCLUSION: In this nationally representative sample of older US adults, cancer survivors had lower DSST scores than non-survivors and had more self-reported problems with memory or confusion. PMID- 26559194 TI - Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies: a single-institution study of 225 cases. AB - Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum beta-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration (P = 0.0264 and P < 0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies. PMID- 26559195 TI - Regorafenib in the treatment of colorectal cancer. AB - INTRODUCTION: Colorectal cancer (CRC) is among the most frequently diagnosed malignancies, and is commonly associated with metastatic disease at presentation. While chemotherapy represents a mainstay of management, options at the time of disease progression are limited. Regorafenib is a novel multikinase inhibitor which has been evaluated for patients with chemo-refractory metastatic CRC (mCRC) and is currently approved for use in a last-line-of-treatment setting. AREAS COVERED: Articles searchable on MEDLINE/PubMed were reviewed to provide context for use of regorafenib in the management of mCRC. Specific drug properties are discussed, including chemistry, pharmacodynamics, pharmacokinetics, and metabolism. Additionally, clinical efficacy is reported with consideration of Phases I-III data. EXPERT OPINION: Phase III evaluation has confirmed the efficacy of regorafenib for patients with chemo-refractory mCRC. Importantly, the rapid accrual of the CORRECT trial revealed the degree of unmet need for this patient population, and proved that it was feasible to compare novel agents to placebo when multiple lines of standard therapy have failed. In the coming years, the role of regorafenib in the management of mCRC should be further clarified, especially through identification of the patient population with greatest anticipated benefit and exploration of its use as an adjuvant or maintenance agent. PMID- 26559198 TI - A complementary method to CD4 counting: measurement of CD4+/CD8+ T lymphocyte ratio in a tandem affinity microfluidic system. AB - We describe a tandem affinity microfluidic separation that measures the ratio of CD4+/CD8+ T lymphocytes from blood samples. It is performed by injecting 2 MUL of lysed blood samples at 1800-2700 cells MUL(-1) into a microfluidic device containing two serially linked affinity regions, followed with a stop flow incubation that captures CD4+/CD8+ T lymphocytes on the corresponding affinity regions. Fluorophore conjugated antibodies are then injected at a controlled shear stress of 1.7 dyn cm(-2) to label target cells while eluting non-specific cells; and at last the CD4/CD8 ratio is calculated after the cell enumeration. The ratio of CD4+/CD8+ T lymphocytes achieved by our tandem affinity microfluidic system was in close agreement with that performed using conventional flow cytometry (R (2) = 0.97) over a wide range (0.4-2.5) that covered the reference values from immune deficient patients to healthy people. This approach may represent an inexpensive and powerful tool in diagnosis of immunodeficiency disorders including HIV or mycobacterium tuberculosis. PMID- 26559197 TI - Curcumin protects against nicotine-induced stress during protein malnutrition in female rat through immunomodulation with cellular amelioration. AB - Nicotine aggravates many chronic inflammatory disorders in females under the protein-malnourished conditions because women are more susceptible to nicotine induced diseases due to their low innate immunity. Although curcumin have been found to obliterate the nicotine-induced disorders through its anti-nicotinic activity under the protein-malnourished condition, the exact mechanism of protective action of curcumin is still unclear. Female Wister rats maintained under the normal and protein-restricted diets in two separate groups were injected with the effective dose of nicotine-tartrate (2.5 mg/kg body weight/day, subcutaneously) and supplemented with the effective dose of curcumin (80 mg/kg body weight/day, orally) for 21 days. The morphology of red blood cells (RBCs), molecular docking, lipid profile and activities of antioxidant enzymes in tissues, cytokines profiling (T helper cell type 1; and T helper cell type 2), mRNA and protein expression of cytokines, transcription factors (activator protein 1), regulatory molecule (P(53)), growth factors (Granulocyte-macrophage colony-stimulating factor; Transforming growth factor beta) were determined to establish the mechanism of actions of curcumin against the nicotine-mediated stress in the protein-malnourished rats. This study revealed that curcumin bound to the Histidine 87 residues of haemoglobin with a greater binding affinity and significantly protected the RBCs against nicotine-induced damage. Furthermore, the nicotine-mediated disruption of Th1/Th2 balance through upregulation and downregulation of different factors was effectively restored by curcumin under the protein-malnourished conditions. The study demonstrated that curcumin was a potent protective compound against the nicotine-induced stress and offered a probable biochemical and immunomodulatory mechanism of protective action of curcumin. PMID- 26559200 TI - Comment on Alquraini et al.: reliability of Canadian Emergency Department Triage and Acuity Scale (CTAS) in Saudi Arabia. AB - It is very common to examine reliability of triage scales using (weighted) kappa statistics. The point is that weighted kappa has grossly underestimated disagreements by one category and put more emphasis on extreme category disagreements; therefore, low prevalence of critically-ill and non-urgent patients has excluded the effect of extreme categories disagreement from calculated kappa coefficient and also contributed to significant overestimation. As a result, weighted kappa coefficient as an estimate of scale reliability is overestimated by the anchoring effect. PMID- 26559199 TI - Retina-on-a-chip: a microfluidic platform for point access signaling studies. AB - We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 MUm diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina. PMID- 26559202 TI - [Editorial]. PMID- 26559201 TI - Pharmacological approaches to CNS vasculitis: where are we at now? AB - The diagnosis and treatment of central nervous system (CNS) vasculitis is extremely challenging. Several conditions can mimic CNS vasculitis and require totally different treatment. CNS vasculitis, once confirmed, may result from infections or systemic diseases that will warrant specific treatments, or, more rarely, be primary and isolated (PCNSV). Prospective trials to help determine the optimal treatment for PCNSV are lacking, but data from several cohorts have provided seminal data on its management. The consensus is to use glucocorticoids as first-line agents, combined with additional immunosuppressants for the most severe cases, mainly cyclophosphamide for induction, followed by less-toxic maintenance therapy with azathioprine, methotrexate, or mycophenolate mofetil. The recent identification of PCNSV subgroups and predictors of outcomes might help in deciding the adequate treatment for each patient, keeping in mind that these data are based on a small number of patients. Other agents and biologics can be considered for patients with relapsing and/or refractory disease, but evidence is limited. In practice, the diagnosis must be re-questioned in patients with PCNSV refractory to standard treatment, especially with diagnoses not based on pathology. PMID- 26559203 TI - [History of the department of Psychiatry at the University of Montreal]. AB - In its current form, the Departement de psychiatrie at the Universite de Montreal (UdeM) was created in 1964. The first person to have headed was Dr. Gerard Beaudoin... Between 1948 and 1964, several others psychiatrists were heading the Departement without necessary bearing a particular title.The directors of the Departement from 1951 to now were: Drs. Fernand Cote, Camille Laurin, Gerard Beaudoin, Yvon Gauthier, Arthur Amyot, Francis Borgeat, Hugues Cormier, Sylvain Palardy, Jean Hebert, and Emmanuel Stip.When the Departement opened, it was the second institution in Montreal that was training psychiatrists. During the first year, there were 3 psychiatric residents, but within 20 years this number had increased to 63. From the early years, teaching psychiatry to residents, and subsequently to all UdeM medical students, has been a priority in the Departement, and over the years many psychiatrists trained at UdeM have attained leadership positions elsewhere. The Departement attained an early reputation for excellence in both clinical and basic research.The strengths the Departement developed in its early years in clinical psychopharmacology, in basic research in neurotransmitters, sleep, cognition, forensic, and in community psychiatry have been augmented more recently with active programs in psychotherapy research, substance abuse research, psychoneuroendocrinology, developmental aspects of behavior, genetics, epigenetics as well as the study of the brain through a variety of brain scanning techniques.The history of the Departement de psychiatrie de l'Universite de Montreal is largely dependent on that of each of the institutions affiliated to the Universite: the Pavillon Albert-Prevost de l'Hopital du Sacre-Coeur de Montreal (HSCM), the Institut universitaire en sante mentale de Montreal (IUSMM) and the CHU Sainte-Justine. We must also remember that the discovery of the potentiating of lithium by antidepressants was made by Dr. Demontigny team at the Hopital Louis-H. Lafontaine (now IUSMM). Significant advances related to the interaction between the psychoanalytic movement and community psychiatry were greatly influenced by the work at the Pavillon Albert Prevost and the emergence of behavioral therapies (Dr. Yves Lamontagne) and cognitive studies conducted by the Hopital Louis-H. Lafontaine. Great discoveries about sleep were performed at the Hopital du Sacre-Coeur de Montreal by teams gathered around Jacques-Yves Montplaisir.We also recall that two ministers from the Quebec government with important political responsibilities were members or directors of the Departement de psychiatrie. These are Drs. Camille Laurin and Denis Lazure.The Departement aims to strengthen clinical and basic research by contributing new knowledge that will improve care for people with mental disorders. These efforts benefit both patients and the medical students and residents being trained to care for them. The Departement remains committed to its program, to pre-doctoral education (ensuring that all medical students at the Universite are trained to recognize, diagnose, and be familiar with treatment options for mental disorders), to post-doctoral education for future psychiatrists, and to the care of Quebec's patients.For over 50 years, the academic department has played a key role in attracting and recruiting excellent academic and clinical resources to staff the programs and services of our hospital partners. PMID- 26559204 TI - [To become a psychiatrist in Quebec in the 50s to 60s]. AB - The author is the witness of a historic period of the psychiatry in the province of Quebec in Canada, widely francophone. He describes the context, the training in psychiatry, and the care. In Quebec, in the 1950s, the psychiatry did not exist as such as speciality. There was however a discipline: the neuropsychiatry. It was managed by the neurologists who agreed to take care of cases of psychiatry, which few doctors wanted to treat at this moment. The religious and rural society in Quebec of the 1950s got ready for the "Revolution tranquille". The latter finally burst after 1960. But the artistic environment was already in full excitement, and from 1948, it showed its opposition to the values which were current with the publication of the Refus global. Among the signatories of the latter, we find Bruno Cormier as medical student who will become, after 1950, a psychiatrist and a psychoanalyst. To become a psychiatrist, it was necessary to be trained as an intern in a residency program in the USA, UK or in France. The residency in the United States in the 1950s represented a great adventure for the young doctors of Quebec, especially for the French speakers. At the end of 1950s, the pharmacology emerged. However, he described his own experience as an observer or an actor with ECT, Sakel cure and about the lobotomy. PMID- 26559205 TI - [Madness is Conforming to One's Own Norms, and No Others: Psychiatry in Post-war Quebec]. AB - In the early 1950s, both the publication of the first Diagnostic and Statistical Manual (DSM-I) and the advent of psychopharmacology - particularly the development of chlorpromazine (Thorazine - RP4650) - set the stage for models of psychiatric thought, research and practice that remain dominant today. It was during this pivotal period, in 1955, that the Departement de psychiatrie de l'Universite de Montreal was founded by a cohort of young researchers newly arrived from well-known universities in France and the northeastern United States. This influential group quickly became staunch critics of the province's religion-based asylum system and lobbied for a government review that culminated into the 1962 Commission d'etude des hopitaux psychiatriques (popularly known as the Bedard Report). What followed in Quebec between 1965 and 1975 was the secularization of psychiatric institutions and widespread deinstitutionalization. This paper illuminates cultural changes and intellectual shifts that have been overlooked in historical studies of post-war psychiatry by exploring the expansion of such "anti-psychiatry" schools of thought in Quebec in this period. PMID- 26559206 TI - [What is the future of the Louis-H. Lafontaine Hospital?]. AB - Most of the time, a government manages in order to keep the public support and tries to make others look responsible for the difficulties generated by his inertia. The history of various changes in the transformation of of the Hopital Saint-Jean-de-Dieu to the Hopital Louis-Hippolyte-Lafontaine had led to three administrative guardianships illustrates this, if we consider that the first one avoid such name. This merely about the events that led from the first one to the second guardianship. PMID- 26559207 TI - [From the Ecole Gamelin to the Riviere-des-Prairies Hospital: from scandals to its restoration]. AB - The history of the Hopital Riviere-des-Prairies from its origins up to today is like the history of psychiatric institutions in French Canada: it constitutes a condensed of nearly 80 years: evolution marked by alternating generous initiatives and regrettable events if not scandals with nevertheless a recent successful evolution in its participation within the Institut universitaire en sante de Montreal. From the institutional presented case, this story invites us to keep in mind on the vulnerability of the psychiatric institutions to the perversion of its innovations. PMID- 26559208 TI - [The role of psychoanalysts in the history of the department of Psychiatry of the University of Montreal]. AB - OBJECTIVES: The authors want to illustrate how psychoanalysis or best a certain psychoanalytical vision without dogmatism and theoretical exclusivism have played an important role in the history of the university department. METHODS: The authors have made a recension of the principal activities of three psychoanalysts and their immediate collaborators: Dr. Camille Laurin, Dr. Yvon Gauthier and Dr. Arthur Amyot. RESULTS: Dr. Laurin permitted psychiatry to become a distinct discipline from neurology. He greatly emphasized the pre-graduate and post graduate cursus: he has also endowed the department with the first complete program of residency. Dr. Gauthier, in a way, built the administrative organization by creating its principal committees. Dr. Amyot really formed the university network by integrating the different hospitals in the projects and the decisions of the department. CONCLUSION: Each one, in his own way, contributed to one of the distinctive marks of the department, that is the importance given to psychotherapy training. In so doing, they favoured the transmission of psychiatry in which the bio-psycho-social perspective is not a vain word. PMID- 26559209 TI - [History lived, history told: Psychiatrists' perspectives on the development of the department of Psychiatry of the University of Montreal]. AB - OBJECTIVES: We have interviewed psychiatrists from different generations at the Departement de psychiatrie de l'Universite de Montreal to discern the history lived and told by those who have made (and still make) the history of the Department. The goal of this approach was to grasp the past in order to enlighten the future of the Departement de psychiatrie de l'Universite de Montreal. METHOD: Thirteen psychiatrists of the department have been interviewed about their perspective on the history of the Departement de psychiatrie de l'Universite de Montreal. RESULTS: Interviews have identified an issue in the communication of history among the Department. Indeed, most of the younger psychiatrists were not aware of some of the main events and figures which were part of the development of the Department. The older psychiatrists mention Dr Camille Laurin as an important figure of the Department's early stages. Psychotherapy, education and clinical practice appear as key aspects of the Department's history. CONCLUSION: Many aspects of the Department's history appear unknown to the younger psychiatrists. A course on History of Psychiatry, including the Department's history, would be a great addition to the psychiatry residency program. PMID- 26559210 TI - [Fifty years of public service for Quebec community psychiatry services. Part I]. AB - This essay comprises 2 parts. It aims to recognize the public service of psychiatrists of the Departement de psychiatrie de l'Universite de Montreal who served at the provincial level of the Ministry of Health and Social Services for deinstitutionalisation of policies and organisation of services, at the service of people with severe mental disorders. First with Dr. Camille Laurin post-face of the 1962 book Les fous crient au secours! (Mentally ill patients cry for help); then the insight on the latest phase of differentiated specialised clinics by Dr. Denis Lazure, who participated in 1962 to the Bedard, Lazure, Roberts commission that launched community psychiatry, but who will also be Social Affairs Minister in the late '70 s; Dr. Arthur Amyot will sail through the budgetary issues when in the beginning of the '80s the mental health directorate was under Social Affairs; Dr. Luc Blanchet will be associated to a rich production of interdisciplinary reports by the advisory Mental Health Committee until its dismissal in 2003; and finally, Dr. Andre Delorme, who probably has the record of longevity at the head of the mental health directorate, transferred in 2003 under the deputy minister for medical and university affairs.The essay will propose since the beginning a grid or referential of four health services analysis. First; the arguments for community care by British and Italian psychiatrists and researchers, Thornicroft and Tansella. Second; system issues of mental health reforms proposed by Canadian psychiatric nurse and researcher Paula Goering. Third; the model of socio-political regulation of health system proposed by the Universite de Montreal' health administration researcher Dr. Andre-Pierre Contandriopoulos; and Fourth; the structural tension between the medical and social sector signaled by the American medical sociologist, Leutz.The same phases of deinstitutionalization in other countries as UK, took place as followed: a) the asylum phase (before 1960); b) the psychiatry community (1960-2000); and c) the differentiated system (since 2000). The essay will evidence the long march towards hospitals without walls, interdisciplinary work, tension between cure and rehabilitation and a relative decreasing budget. This in conjunction with vulnerability in organisation and leadership, attributed to tension or burn out has revealed system deficits like the trans-institution towards homelessness or towards the judiciary system. The essay will conclude with a discussion on the opportunities and challenges of the very new Law 10 that reforms the general governance of the provincial and regional health and social services and hopes for a more balanced mental health care system in Quebec. PMID- 26559211 TI - [Fifty years of public service for Quebec community psychiatry services. Part II (2003-2015 and beyond)]. PMID- 26559212 TI - [Psychiatry in Quebec. Then and now]. AB - This text narrates the evolution, since the 1960s, of different events that marked the history of psychiatry in the French-Canadian province of Quebec. From his personal experience, the author discusses. The evolution of the Department de psychiatric de l'Universite de Montreal fro where were issued more than 1000 psychiatrists who shaped clinical practice and research developments worthy of mention throughout the years. The evolution of diagnostic noselogy from the DSM ii, very influenced by psychoanalysis, to the DSM-5 that is more atheortical, but that is still not based on objective data, which remains a challenge to the etiology of mental illness. The psychiatric drugs that we have learned to prescribe in the past 50 years in a more rational way thanks to a better understanding of their action mechanisms. In reality, there has been no discovery of new drug categories; rather it is the way we prescribe medication that evolved. The great adventure of the first textbook of Quebec psychiatry, which was first published in 1980, and is forthcoming in its 4th edition in 2015 in an improved and expanded format. The forthcoming version takes into consideration the developments in psychiatry. The creation of the Young Adults Clinic in 1988, providing treatment and rehabilitation to young adults in the early stages of schizophrenia, as well as psychoeducational support and information to heir family members. Through the years, this clinic had a considerable acknowledgement in Quebec and other French-speaking nations. PMID- 26559213 TI - [The changes in values and beliefs through the first 50 years of the department of Psychiatry at the University of Montreal]. AB - This essay attempts to describe and discuss the major changes in values and fundamental beliefs related to clinical practice within the Departement de psychiatrie de l'Universite de Montreal since its creation fifty years ago.Being an essay, the methods include shared recollections, discussions with colleagues, especially between the co-authors, and the study of some documents related to the practice of psychiatry 40 to 50 years ago.Five major axes of change are proposed: 1- From psychoanalysis to brain diseases, 2- From "Can a non-physician practice psychoanalysis?" to "Can a psychiatrist still perform psychotherapy?" 3- From continuity of care to episodes of treatment, 4- From treatment first to repeated assessments of patients, 5- From love that can heal and repair to a taboo of love.Finally it is suggested that the increasing emphasis on psychopharmacology and on DSM classifications has contributed to a shift from attempts to understand the intimate nature of symptoms and suffering to a priority given to rather mechanical clinical assessments in search of "objective" criteria. PMID- 26559214 TI - [Is psychiatry relevant in autism? A brief historical perspective on the role of psychiatry in diagnosis, and support to autistic people]. AB - Based on an overview of the recent history of professional roles in autism diagnosis and support in the province of Quebec, this paper supports the view that hearing what autistic people say, combined with interdisciplinary, but hierarchically ruled task sharing in clinical settings, and to a pacific confrontation between scientific and clinical demands, prevents the high jacking of autism for corporatist or ideological purposes. PMID- 26559215 TI - [Crossroads, 50 years of child care]. AB - INTRODUCTION: Through a journey in time, we propose to revisit the birth of the first mental health care settings for children with mental disorders affiliated with Universite de Montreal, Quebec, Canada. METHODS: The main centers of child psychiatry affiliated with the Universite de Montreal are presented with the outstanding figures of the time. RESULTS: Philosophical transitions and therapeutic paradigms are also briefly discussed. The creation of subspecialty clinics and training approved by the Royal College of Psychiatry of Child and Adolescent marked the contemporary era. CONCLUSION: The contribution to training medical students, residents and researchers in the field of Child and Adolescent Psychiatry reflects the important milestones since the foundation of the Universite de Montreal Department of Psychiatry. So much achieved in half a century. PMID- 26559216 TI - [The history of geriatric psychiatry at the University of Montreal: Pioneers, milestones, and future outlook]. AB - OBJECTIVES: Geriatric psychiatry became an official psychiatric subspecialty in Canada in 2009. The first board examinations from the Royal College of Physicians and Surgeons of Canada (RCPSC) took place in 2013. Geriatric Psychiatry focuses on the assessment, diagnosis, and treatment of complex mental disorders in late life, a time when the interface between physical and mental health issues often adds a new level of complexity.Little has been written on the history of geriatric psychiatry in Quebec and in Canada. A lesser-known aspect is that from the 1970's onwards, the department of psychiatry at the Universite de Montreal (UdeM) and its network of teaching hospitals have played a pioneering role in the development of geriatric psychiatry services and training. We seek to recount the history of geriatric psychiatry at UdeM, by tracing the milestones and identifying the main actors responsible for its development, from the inception of the department of psychiatry 50 years ago. This leads us to share reflections on some of the issues geriatric psychiatry is facing in Quebec. METHODS: We interviewed several key actors, past and present, of geriatric psychiatry at UdeM. We read through relevant sources such as articles and monographs on the local history of psychiatric services, information bulletins and annual reports from hospitals and from UdeM, as well as other documentation from personal archives. RESULTS: One of the very first geriatric psychiatry services in Canada was founded in 1978 at the Institut universitaire en sante mentale de Montreal, with a dedicated inpatient unit for new admissions of elderly psychiatric patients. A geriatric psychiatry outpatient clinic was inaugurated the same year at the Pavillon Albert-Prevost. Throughout the years, geriatric psychiatry services were also developed in the remaining hospital sites affiliated with the department of psychiatry at the UdeM (Hopital Maisonneuve-Rosemont, Centre hospitalier de l'Universite de Montreal, Institut universitaire de geriatrie de Montreal), driven by dedicated individuals, in accordance with their respective historical background and mission. Clinical training is provided in each of these sites for medical students, psychiatry residents and more recently, for future geriatric psychiatrists. In 2014, the geriatric psychiatry residency program at UdeM was the first to be accredited in Quebec by the RCPSC, as well as the first French language geriatric psychiatry program in North America. CONCLUSION: Geriatric psychiatry in 2015 is a burgeoning field, in a challenging demographic context. Despite the clinical need, major obstacles remain, particularly in the absence of specific geriatric psychiatry positions. Furthermore, the Quebec healthcare system is going through a major restructuration in 2015, adding to the uncertainty. The 50th anniversary of the department of psychiatry at UdeM is an opportunity to underline the contribution of UdeM to the development of geriatric psychiatry in Quebec, and to emphasize the specific needs of the elderly in terms of mental health care and geriatric psychiatry services. PMID- 26559217 TI - [The Institute Philippe-Pinel and the department of Psychiatry of the University of Montreal: intricate paths]. AB - The Institute Philippe-Pinel (IPPM) and the Departement de psychiatrie de l'Universite de Montreal, who are both celebrating their 50 years, have intricated paths and a long history of collaboration. Since its conception (1964), the Institute Philippe-Pinel was planned to become a site for training and teaching in the bosom of the Universite de Montreal.Unique in its mission to offer state of the art psychiatric care and forensic assessments to patients presenting a high risk of violence, the Institute Philippe-Pinel, throughout the years, was also able to leave its mark by the way of academic teaching to psychiatric residents and trainees of all disciplines, of organizing national and international conferences, of research and by the publication of numerous articles and books in the field of forensic psychiatry.With, from its beginning, psychiatrists at its helm, the Institute Philippe-Pinel has at all times greatly contributed to the academic activity of the department. Highly committed psychiatric clinicians and professors were always involved at all levels of the psychiatric department. With the coming of the forensic subspecialty, the commitment and influence can only continue. PMID- 26559218 TI - [Sleep Medicine: 1965 to 2015]. AB - The Departement de psychiatrie de l'Universite de Montreal houses one of the first sleep centers founded 40 years ago. This center contributed to virtually every aspect of sleep medicine. It grew considerably over time to become one of the largest sleep centers worldwide. It is now called the Center for Advanced Research in Sleep Medicine (CARSM). Fourteen researchers and more than 30 research PhDs and postdoctoral fellows are working together in a 1,500 square meter facility that includes separate units for fundamental and clinical studies and for the sleep disorders clinic. It has 10 polysomnographic recording rooms, 3 isolated units devoted to chronobiological studies, a high resolution SPECT imaging laboratory specifically devoted to sleep research, a high-density EEG unit and a psychophysiological laboratory to study the interaction between pain and sleep. This article relates the history of the CARSM and also presents a personal sleep odyssey.The CARSM has been very active in the description of clinical features and definitions of the phenotype of most sleep disorders. It contributed specifically to the development of diagnostic tools in narcolepsy (the multiple sleep latency test in different age groups), in nocturnal epilepsy (development of a method to localize the primary focus using in-depth electrodes recording during rapid eye movement sleep), in sleep bruxism (a method for scoring masticatory muscle activity during sleep and definition of cut-off values), in the restless legs syndrome (RLS: the suggested immobilisation test), in sleepwalking (sleep deprivation and experimental awakenings) and REM sleep behaviour disorder (RBD: development of the first polygraphic method to diagnose RBD).The CARSM also contributed to the knowledge on the epidemiology of sleep disorders, conducting the first population-based prevalence study of RLS and of sleep bruxism. Researchers at the CARMS also looked at the impact of sleep disorders like narcolepsy, RLS, sleep apnea and the parasomnias on daytime cognitive functions and cardiovascular health. The CARSM collaborates with researchers throughout the world to elucidate the genetic bases of several disorders, especially narcolepsy, RLS, RBD and parasomnias in children and adults, through large well-defined cohorts of patients and normal subjects.Finally, the CARSM has made original contributions to the development of new treatments of sleep disorders, especially the dopaminergic treatments of RLS (first with levodopa and then with pramipexole). Current research also involves the identification of prodromal markers of Parkinson disease and dementia in patients with RBD as to build a ready-to trial cohort to test the efficacy of neuroprotective agents.In summary, the CARSM is a center dedicated to basic and clinical research on sleep and circadian rhythms. It is located at the Hopital du Sacre-Coeur de Montreal but involves several other researchers at the Universite de Montreal and at other universities in Canada and in the world. PMID- 26559219 TI - [Treatment of sleep disorders in children with a psychiatric diagnosis]. AB - OBJECTIVES: Health sciences suffer from insomnia: experts too often concentrate their efforts on the wake state. Fortunately enough, some of them have taken the road towards the "Dark Third of Life": sleep. This article gives an historical account of the development of the first Canadian sleep disorders laboratory and clinic specifically and selectively designed for children and adolescents with a psychiatric diagnosis. It then stresses the importance of sleep in children bearing a psychiatric diagnosis and summarizes therapeutic strategies. METHODS: Data-on-file and selective review of literature. RESULTS: An innovative scheme matching sleep psychologists and psychiatrists with expertise in neurodevelopmental disorders led to the creation of a sleep research laboratory on mental health disorders. The initial research projects on the sleep and dreams of patients with schizophrenia and persons with autism are summarized. The Sleep Disorders Clinic for Children and Adolescents was then created at the Hopital Riviere-des-Prairies, leading to much needed activities focused on youth. Indeed, sleep disorders show a high prevalence in children with a psychiatric diagnosis and the literature shows that these children have an increased sensitivity for diurnal effects of poor sleep. The main sleep-relevant issues at stake are reviewed, including the high frequency of sleep disorders in pedopsychiatric patients. Clinical challenges are described and the operating mode of the Sleep Disorders Clinic is illustrated. CONCLUSION: Sleep disorders and their effects on daytime functioning need to be assessed in children with a psychiatric diagnosis in order to generate a full clinical picture. Appropriate tools and know-how are readily available in order to achieve this goal. PMID- 26559220 TI - [The history of the Science of Stress: From Hans Selye to the discovery of anti inflammatory medication]. AB - To make an important scientific discovery that will make history takes a lot of determination, creativity, perseverance and luck! The story behind the discovery of stress and its biological basis is a fascinating one that places Dr. Hans Selye in the forefront. Dr. Selye was a great scientist that taught at the Universite de Montreal from 1945 to his death in 1982. Dr. Selye was curious and hard working. He was determined to understand how various disorders can lead to similar physical manifestations, and this interest led him to discover the role of the adrenal glands involved in the stress response and to better understand the effects of glucocorticoids on the body. Today, the science of stress is based on the foundations established by Dr. Selye. In celebration of the 50th anniversary of the Departement de psychiatrie de l'Universite de Montreal, and the special issue of the Revue Sante Mentale au Quebec, this historical review summarizes the discoveries of this great scientist who worked in Quebec. PMID- 26559221 TI - ["Les Impatients": expression through art]. AB - The organization called "Les Impatients" was founded in 1992. Using a unique model, Les Impatients welcomes those with mental health issues who would like to express themselves through art. Les Impatients offers free creative workshops and encourages exchanges with the community through the sharing of its participants' creations. The name Les Impatients reinforces the idea that the organization does not consider those attending its workshops as patients, but rather creators who are eager to heal, develop their craft and find their place in society. The participants contribute to the collective objective of breaking down the stigma that surrounds mental illness.Les Impatients collaborates with various mental health organizations in Quebec, such as the Institut universitaire en sante mentale de Montreal (IUSMM) affiliated to the Universite de Montreal, Douglas Mental Health University Institute (DMHUI), the Centre de sante et services sociaux Drummond (CSSS Drummond) and the Centre de sante et services sociaux Pierre-Boucher (CSSS Pierre-Boucher). Les Impatients offers more than 48 workshops in eight different locations to around 450 participants each week.Dissemination activities, remarkable events, original projects: Les Impatients stands out through its realizations. Examples are exhibitions, collections of love letters, comic books, CD, concerts, and reading nights. The organization's originality resides in the exploration of the links between the work of the participants and that of professional artists. An illustration of this interest is the annual Parle-moi d'amour auction-exhibition, which has been one of Les Impatients' major events since 1999.As part of its mission, Les Impatients conserves the works of art created by the participants during the workshops. Its collection includes more than 15,000 works of art from Les Impatients as well as pieces donated by collectors of unconventional art, commonly known as "art brut" or "outsider art". The Collection is characterized by its scientific and artistic potential as well as its connection with the art brut/outsider art movement. That makes it an exciting endeavour for the world of art and social sciences.Les Impatients workshops are appreciated by the participants because they improve self-esteem, stimulate creativity and curiosity, break isolation, contribute to develop a sense of belonging and reduce both the frequency and the length of hospitalization. For these reasons and many more, many participants have reported the positive impacts of their involvement in the arts on their recovery. The innovative activities can also be seen as enhancing the patients' recovery process.Pioneers in the field of recovery, Les Impatients is a forum where the participants, their loved ones, the team, the artists and the community can meet and exchange. Those encounters constitute great opportunities to break the stigma that surrounds mental illness, one of Les Impatients' core objectives. PMID- 26559222 TI - [Fifty years of residency in Psychiatry at the University of Montreal: relevance and necessity of the Residents' Association]. AB - OBJECTIVES: In the context of the fiftieth anniversary celebrations of the Departement de psychiatrie de l'Universite de Montreal, the present article offers to retrace the history of the Psychiatry Resident's Association (ARPUM). Since the Association's activities and demands reflected the concerns of the time, a depiction of the Residency Program and exploration of the historical and administrative context, in each key period, is also undertaken. METHODS: Multiple psychiatrists from every decade, who were once active members of the Association, were interviewed and asked to describe the Residency Program at their time, with its positive and negative aspects, based on their own personal experience as a resident, but also as a member of the organization. The interviewees were also invited to share their recollections of the various Association's demands, representations, activities and functioning, depending on the issues and periods. Various private and public archives were also used, in order to contextualize the residents' experiences and the Association's work. RESULTS: A brief exploration of the historical and political context that led to the creation of the organization is explained. Training and working conditions of residents at that time are reported, enabling the understanding of the first demands when the group was born. Historical jumps are then proposed, from decades to decades, in order to depict key issues, whether they were academic, clinical or organizational, through which the Association worked, over the evolution of the Residency Program. The internal functioning and its occasional problems throughout the years are also described, as is the role in organizing social and educational events. CONCLUSIONS: The Residency Program is in constant mutation, and the Association has played its part in shaping the psychiatric training at the Universite de Montreal. Multiple positive and tangible impacts were and are still made possible from the collaborative work between the Departement de psychiatrie, the Residency Program and the Resident's Association. PMID- 26559223 TI - Personalizing therapy for multidrug resistant TB: the potential of Rapid Whole Genome Sequencing. AB - Multidrug resistant tuberculosis is an increasing problem globally. The current gold standard in drug sensitivity testing is slow and cumbersome. To tackle drug resistance effectively, a more rapid method of testing is required. Current molecular tests are fast, but only offer information on a limited number of genetic loci. Whole genome sequencing presents an attractive alternative that can provide comprehensive, clinically relevant information on all described loci. Although the standard approach to whole genome sequencing of Mycobacterium tuberculosis is slow due to the requirement of culture, this article will describe recent advances that mean it has the potential to provide results within days. PMID- 26559225 TI - Electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength after stroke. AB - BACKGROUND: Electromechanical and robot-assisted arm training devices are used in rehabilitation, and may help to improve arm function after stroke. OBJECTIVES: To assess the effectiveness of electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength in people after stroke. We also assessed the acceptability and safety of the therapy. SEARCH METHODS: We searched the Cochrane Stroke Group's Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 3), MEDLINE (1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), SPORTDiscus (1949 to March 2015), PEDro (searched April 2015), Compendex (1972 to March 2015), and Inspec (1969 to March 2015). We also handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trialists, experts, and researchers in our field, as well as manufacturers of commercial devices. SELECTION CRITERIA: Randomised controlled trials comparing electromechanical and robot-assisted arm training for recovery of arm function with other rehabilitation or placebo interventions, or no treatment, for people after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and risk of bias, and extracted data. We contacted trialists for additional information. We analysed the results as standardised mean differences (SMDs) for continuous variables and risk differences (RDs) for dichotomous variables. MAIN RESULTS: We included 34 trials (involving 1160 participants) in this update of our review. Electromechanical and robot-assisted arm training improved activities of daily living scores (SMD 0.37, 95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I2 = 62%), arm function (SMD 0.35, 95% CI 0.18 to 0.51, P < 0.0001, I2 = 36%), and arm muscle strength (SMD 0.36, 95% CI 0.01 to 0.70, P = 0.04, I2 = 72%), but the quality of the evidence was low to very low. Electromechanical and robot-assisted arm training did not increase the risk of participant drop-out (RD 0.00, 95% CI -0.02 to 0.03, P = 0.84, I2 = 0%) with moderate-quality evidence, and adverse events were rare. AUTHORS' CONCLUSIONS: People who receive electromechanical and robot-assisted arm and hand training after stroke might improve their activities of daily living, arm and hand function, and arm and hand muscle strength. However, the results must be interpreted with caution because the quality of the evidence was low to very low, and there were variations between the trials in the intensity, duration, and amount of training; type of treatment; and participant characteristics. PMID- 26559226 TI - Roles of Complement C1q in Pneumococcus-Host Interactions. AB - The fight between a human host and a bacterial pathogen is highly complicated; each party tries to outshine the other in the race for survival. In humans, the innate immune system--in particular the complement system--functions as the first line of defence against invading pathogens. During the course of evolution, however, pathogens, in order to survive and perpetuate within a host, developed multiple strategies to counteract the host complement system and to colonize. One such pathogen is Streptococcus pneumoniae (pneumococcus), a gram-positive bacterial pathogen often commensal in the human respiratory tract. Depending on the host's susceptibility, pneumococci can transform into an infectious agent, disseminating within the human host and causing mild to life-threatening diseases. This transition from commensal to infectious agent is a highly complex process, and understanding of this mechanism is essential in controlling the pathogenicity of pneumococci. Using its intricate arsenal of weapons, such as surface-presenting adhesins as well as recruitment of host factor, pneumococci successfully colonize the host, a prerequisite for establishing infection. This review describes C1q, the first subunit of the classical complement pathway, and its role in pneumococcus-host interactions, whereby pneumococci exploit C1q as a molecular bridge facilitating host cellular adherence and invasion, a function not akin to the role of C1q in the defence mechanism. PMID- 26559227 TI - Understanding Lung Immunopathology Caused by the Human Metapneumovirus: Implications for Rational Vaccine Design. AB - Acute respiratory tract infections (ARTIs) are the major cause of child mortality worldwide. The human metapneumovirus (hMPV) is one of the leading causes of child hospitalizations due to pneumonia. The adaptive immune response generated by the host against hMPV is usually inefficient at protecting from reinfections, which is repeat throughout life, from childhood to old age. Despite considerable research efforts, to date there are no licensed vaccines to prevent respiratory disease caused by hMPV infection. In this article we review current vaccine strategies tested in animal models and the implication of such studies in understanding the different immune cell populations that contribute to hMPV clearance and the prevention and resolution of lung inflammation upon exposure to the virus. PMID- 26559224 TI - Intracellular trafficking pathways in silver nanoparticle uptake and toxicity in Caenorhabditis elegans. AB - We used the nematode Caenorhabditis elegans to study the roles of endocytosis and lysosomal function in uptake and subsequent toxicity of silver nanoparticles (AgNP) in vivo. To focus on AgNP uptake and effects rather than silver ion (AgNO3) effects, we used a minimally dissolvable AgNP, citrate-coated AgNPs (CIT AgNPs). We found that the clathrin-mediated endocytosis inhibitor chlorpromazine reduced the toxicity of CIT-AgNPs but not AgNO3. We also tested the sensitivity of three endocytosis-deficient mutants (rme-1, rme-6 and rme-8) and two lysosomal function deficient mutants (cup-5 and glo-1) as compared to wild-type (N2 strain). One of the endocytosis-deficient mutants (rme-6) took up less silver and was resistant to the acute toxicity of CIT-AgNPs compared to N2s. None of those mutants showed altered sensitivity to AgNO3. Lysosome and lysosome-related organelle mutants were more sensitive to the growth-inhibiting effects of both CIT-AgNPs and AgNO3. Our study provides mechanistic evidence suggesting that early endosome formation is necessary for AgNP-induced toxicity in vivo, as rme-6 mutants were less sensitive to the toxic effects of AgNPs than C. elegans with mutations involved in later steps in the endocytic process. PMID- 26559228 TI - MHC Genes Linked to Autoimmune Disease. AB - Autoimmune diseases (ADs), or autoinflammatoiy diseases, are growing in complexity as diagnoses improve and many factors escalate disease risk. Considerable genetic similarity is found among ADs, and they are frequently associated with major histocompatibility complex (MHC) genes. However, a given disease may be associated with more than one human leukocyte antigen (HLA) allotype, and a given HLA may be associated with more than one AD. The associations of non-MHC genes with AD present an additional problem, and the situation is further complicated by the role that other factors, such as age, diet, therapeutic drugs, and regional influences, play in disease. This review discusses some of the genetics and biochemistry of HLA-linked AD and inflammation, covering some of the best-studied examples and summarizing indicators for class I- and II-mediated disease. However, the scope of this review limits a detailed discussion of all known ADs. PMID- 26559229 TI - Innate Antiviral Immunity against Dengue Virus. AB - Dengue virus (DENV), the most prevalent mosquito-borne viral diseases in humans worldwide, causes dengue fever, a mild form of the disease, as well as dengue hemorrhagic fever/dengue shock syndrome, a more severe form which can be life threatening. The four serotypes of DENV (DENV1-4) are positive-sense, single stranded RNA virus belonging to the Flaviviridae family and are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Together, they are estimated to cause almost 100 million symptomatic cases, 2.1 million cases of dengue hemorrhagic fever/dengue shock syndrome, and 21,000 deaths per year worldwide. There are currently no effective vaccines or antiviral treatment for DENV. Innate immune defenses play a key role in controlling DENV infection in the early stages. Herein we review the innate antiviral immunity against DENV by delineating the intracellular mechanisms of the immune response and the evasion mechanisms evolved by the virus. A better understanding of the innate immune response will impact the development of novel animal models, antiviral drugs as well as potential targeted adjuvants for DENV vaccines. PMID- 26559230 TI - Regulating tissue behaviour with air-cell-based cushions. PMID- 26559231 TI - The role of intravenous drug use in venous leg ulceration. PMID- 26559232 TI - Recommended frequency of ABPI review for patients wearing compression hosiery. AB - This paper is a sequel to the article 'How often should patients in compression have ABPI recorded?' ( Furlong, 2013 ). Monitoring ankle brachial pressure index (ABPI) is essential, especially in those patients wearing compression hosiery, as it can change over time ( Simon et al, 1994 ; Pankhurst, 2004 ), particularly in the presence of peripheral arterial disease (PAD). Leg ulceration caused by venous disease requires graduated compression ( Wounds UK, 2002 ; Anderson, 2008). Once healed, compression hosiery is required to help prevent ulcer recurrence ( Vandongen and Stacey, 2000 ). The Royal College of Nursing ( RCN, 2006 ) guidelines suggest 3-monthly reviews, including ABPI, with no further guidance. Wounds UK (2002) suggests that patients who have ABPI<0.9, diabetes, reduced mobility or symptoms of claudication should have at least 3/12 Doppler, and that those in compression hosiery without complications who are able to report should have vascular assessment yearly. PMID- 26559233 TI - Efficacy of a superabsorbent dressing with Hydration Response Technology. AB - Moderately and heavily exuding wounds are associated with delayed healing and an increased risk of infection. Elevated proteases found in chronic wound fluid keep a sustained state of inflammation. Superabsorbent dressings can absorb large quantities of exudate without losing their structure. Some are also able to bind and sequester proteases and bacteria within their structure. This article summarises the in-vitro and clinical evidence on the efficacy of Cutimed(r) Sorbion(r) Sachet S. The findings indicate that it helps facilitate autolytic debridement, absorbs exudate and reduces inflammation, and thus the risk of infection. PMID- 26559234 TI - Woundcare4Heroes. PMID- 26559235 TI - A 6 month evaluation of a non-powered hybrid mattress replacement system. AB - In 2013, the Royal Cornwall Hospitals NHS Trust undertook a 6-week evaluation of the AtmosAir 4000 non-powered reactive pressure redistribution mattress replacement system to determine its suitability in supporting the prevention of pressure ulcers in high-risk patients (phase one). The results demonstrated that the AtmosAir 4000 mattress system, together with skin assessment and repositioning regimes, met the pressure ulcer preventative needs of patients at high and very high risk of developing pressure ulcers. It also resulted in a notable reduction in the use of dynamic air mattresses. Consequently, 50 AtmosAir 4000 mattresses were purchased for two acute medical wards in the evaluation site, where the majority of patients are elderly with an acute medical condition. This article discusses the second phase where an audit compares the number of hospital-acquired pressure ulcers reported over a 6-month period with the equivalent time period in 2014. Results show that the number of pressure ulcers reduced by 65% and 50% in the two wards. The number of dynamic mattresses used on the two wards reduced significantly from 28 to 7, which represents a 75% reduction in usage. PMID- 26559236 TI - Wound exudate assessment and management: a challenge for clinicans. AB - The production of wound exudate is a natural and normal consequence of healing. However, it is when the constituents, volume and consistency of the exudate alter that problems can occur. This article discusses the different types of exudate, particularly highly viscous exudate, its impact on both the patient and the clinician, and appropriate exudate assessment, effective management and dressing selection. PMID- 26559237 TI - The use of smart technology to deliver efficient and effective pressure-damage education. AB - This article outlines an innovative joint working strategy, as well as a partnership project, between two NHS Foundation Trusts-a community trust and industry partner-to develop a mobile training app to deliver pressure ulcer prevention and management for clinical staff. The aim of the innovation was to enable a new way of delivering education to large numbers of staff by moving away from traditional classroom-based training. The process included development of the app, along with testing and implementation, followed by a review of the qualitative data after the app's implementation. The review takes into account the key outcomes that have had an impact on this method of delivering education, its challenges and how it has been received by clinical staff and patients. PMID- 26559238 TI - Effect of a new compression garment on adherence: results of a patient satisfaction survey. AB - Traditionally, knee-high compression stockings apply a slightly higher pressure at the top band to keep them in place. However, some patients find this uncomfortable, which can affect adherence. The Jobst Opaque SoftFit stocking contains a silicone yarn in the top band, which is designed to keep it in place without exerting extra pressure. A survey was undertaken to determine if the SoftFit stocking was more acceptable to patients than the compression stockings they had worn previously, and to identify its effects on the symptoms of chronic venous disease (CVD). Patients with CVD living in the community were recruited from four federal states in Germany. They wore the test stocking for 7 days. Data collected on days 1 and 7 compared their perceptions of the test stocking with those of the conventional compression stockings worn previously. The results showed that, compared with the previous stockings used, the majority of patients considered the test stocking to be more comfortable at the top band and more likely to stay in place, while many no longer experienced some of the clinical symptoms of CVD such as heavy legs, pain in the legs and itching or dry skin. PMID- 26559239 TI - Wound-bed preparation: the importance of rapid and effective desloughing to promote healing. AB - This article describes effective ways of diagnosing and removing slough from a wound bed. It highlights how slough is a key contributor to wound chronicity, and gives practical clinical information on how to address this. The various methods of removing slough will be discussed including the mechanism of action of dressings and other mechanical methods. The ultimate objective of the article is to put the term desloughing on the clinical agenda and increase clinician familiarity with it. The practical focus of the article will help clinicians select a proven method to facilitate the rapid removal of slough, it is hoped that in doing so this will help to prevent chronicity, reduce the potential for bacterial proliferation and promote rapid and effective wound healing outcomes. PMID- 26559240 TI - Going green: using a bio-cellulose membrane for patients with chronic non-healing wounds. AB - A 20-patient evaluation was undertaken on the most chronic non-healing wounds that had been present in excess of 6 months. Patients were treated with a biotechnology dressing that is provided in a mesh and gel combination. Eighteen of out 20 patients went on to heal. Cost effectiveness examined the cost associated with maintaining non-healing wounds where all alternative therapies had failed. Nursing time both in outpatients and home visits were included. A wide variety of secondary dressings were applied according to clinical preference as the new dressings are designed as a direct wound contact mesh. This is a very new concept to wound care, with initial unit cost being high, but the possibilities of natural plant extracts that can mimic collagen synthesis is exciting. Both the staff and patients have seen a marked improvement, with up to date no recurrence. Further studies need to be undertaken to establish if these early findings are repeatable. PMID- 26559242 TI - Identification of rare high-risk copy number variants affecting the dopamine transporter gene in mental disorders. AB - BACKGROUND: The dopamine transporter, also known as solute carrier 6A3 (SLC6A3), plays an important role in synaptic transmission by regulating the reuptake of dopamine in the synapses. In line with this, variations in the gene encoding this transporter have been linked to both schizophrenia and affective disorders. Recently, copy number variants (CNVs) in SLC6A3 have been identified in healthy subjects but so far, the implication of CNVs affecting this gene in psychiatric diseases has not been addressed. AIMS: In the present study, we aimed to investigate whether CNVs affecting SLC6A3 represent rare high-risk variants of psychiatric disorders. METHODS: We performed a systematic screening for CNVs affecting SLC6A3 in 761 healthy controls, 672 schizophrenia patients, and 194 patients with bipolar disorder in addition to 253 family members from six large pedigrees affected by mental disorders using single nucleotide polymorphism arrays and subsequent verification by real-time polymerase chain reaction. RESULTS: We identified two duplications and one deletion affecting SLC6A3 in the patients, while no such CNVs were identified in any of the controls. The identified CNVs were of different sizes and two affected several genes in addition to SLC6A3. CONCLUSION: Our findings suggest that rare high-risk CNVs affecting the gene encoding the dopamine transporter contribute to the pathogenesis of schizophrenia and affective disorders. PMID- 26559241 TI - Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial. AB - STUDY QUESTION: How effective is supported computerised cognitive behaviour therapy (cCBT) as an adjunct to usual primary care for adults with depression? METHODS: This was a pragmatic, multicentre, three arm, parallel randomised controlled trial with simple randomisation. Treatment allocation was not blinded. Participants were adults with symptoms of depression (score >= 10 on nine item patient health questionnaire, PHQ-9) who were randomised to receive a commercially produced cCBT programme ("Beating the Blues") or a free to use cCBT programme (MoodGYM) in addition to usual GP care. Participants were supported and encouraged to complete the programme via weekly telephone calls. Control participants were offered usual GP care, with no constraints on the range of treatments that could be accessed. The primary outcome was severity of depression assessed with the PHQ-9 at four months. Secondary outcomes included health related quality of life (measured by SF-36) and psychological wellbeing (measured by CORE-OM) at four, 12, and 24 months and depression at 12 and 24 months. STUDY ANSWER AND LIMITATIONS: Participants offered commercial or free to use cCBT experienced no additional improvement in depression compared with usual GP care at four months (odds ratio 1.19 (95% confidence interval 0.75 to 1.88) for Beating the Blues v usual GP care; 0.98 (0.62 to 1.56) for MoodGYM v usual GP care). There was no evidence of an overall difference between either programme compared with usual GP care (0.99 (0.57 to 1.70) and 0.68 (0.42 to 1.10), respectively) at any time point. Commercially provided cCBT conferred no additional benefit over free to use cCBT or usual GP care at any follow-up point. Uptake and use of cCBT was low, despite regular telephone support. Nearly a quarter of participants (24%) had dropped out by four months. The study did not have enough power to detect small differences so these cannot be ruled out. Findings cannot be generalised to cCBT offered with a much higher level of guidance and support. WHAT THIS STUDY ADDS: Supported cCBT does not substantially improve depression outcomes compared with usual GP care alone. In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care. FUNDING, COMPETING INTERESTS, DATA SHARING: Commissioned and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 06/43/05). The authors have no competing interests. Requests for patient level data will be considered by the REEACT trial management groupTrial registration Current Controlled Trials ISRCTN91947481. PMID- 26559243 TI - Health fee exemptions: controversies and misunderstandings around a research programme. Researchers and the public debate. AB - Our research programme on fee exemption policies in Burkina Faso, Mali and Niger involved sensitive topics with strong ideological and political connotations for the decision-makers, for health-workers, and for users. Thus we were confronted with reluctance, criticism, pressures and accusations. Our frank description of the shortcomings of these policies, based on rigorous research, and never polemical or accusatory, surprises political leaders and health managers, who are accustomed to official data, censored evaluations and discourse of justification. PMID- 26559244 TI - A new triterpenoid saponin from Gleditsia sinensis and its antiproliferative activity. AB - Chemical investigation of the anomalous fruits of Gleditsia sinensis led to the isolation and identification of a new triterpenoid saponin, 3-O-beta-D xylopyranosyl-(1 -> 2)-alpha-L-arabinopyranosyl-(1 -> 6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyrano--syl-(1 -> 4)-beta-D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1 -> 3)-beta-D glucopyranosyl ester (1), along with other nine known compounds (2-10). All the isolates from this species were reported for the first time. The structure of Compound 1 was determined by a detailed analysis using various analytical techniques, including 1D and 2D NMR. In vitro antiproliferative activities of Compound 1 on MCF-7 and Hep-G2 tumor cell lines were evaluated. IC50 values against the two cell lines were 9.5 and 11.6 MUM, respectively. PMID- 26559245 TI - Evidence for localized moment picture in Mn-based Heusler compounds. AB - X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD) were used to probe the electronic structure and magnetic moment of Mn in Heusler compounds with different crystallographic structure. The results were compared with theoretical calculations of the magnetic and electronic properties, and it was found that in full and half Heusler alloys, Mn is metallic on both sublattices. The magnetic moment is large and localized when octahedrally coordinated by the main group element, consistent with previous theoretical work, and reduced when the main group coordination is tetrahedral. The magnetic and electronic properties of Mn in full and half Heusler compounds are strongly dependent on the structure and sublattice, a fact that can be exploited to design new materials. PMID- 26559246 TI - Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer: A Meta-analysis. AB - Anxiety and depression are common among patients with cancer, and are often treated with psychological interventions including mindfulness-based therapy.The aim of the study was to perform a meta-analysis of the effectiveness of mindfulness-based interventions for improving anxiety and depression in patients with cancer.Medline, the Cochrane Library, EMBASE, and Google Scholar were searched. The randomized controlled trials designed for patients diagnosed with cancer were included. Mindfulness-based interventions were provided.The outcomes assessed were the changes in anxiety and depression scores from before to after the intervention. The treatment response was determined by calculating the standardized mean difference (SMD) for individual studies and for pooled study results. Subgroup analyses by cancer type, type of therapy, and length of follow up were performed.Seven studies, involving 469 participants who received mindfulness-based interventions and 419 participants in a control group, were included in the meta-analysis. Mindfulness-based stress reduction and art therapy were the most common interventions (5/7 studies). All studies reported anxiety and depression scores. The pooled SMD of the change in anxiety significantly favored mindfulness-based therapy over control treatment (-0.75, 95% confidence interval -1.28, -0.22, P = 0.005). Likewise, the pooled SMD of the change in depression also significantly favored mindfulness-based therapy over control ( 0.90, 95% confidence interval -1.53, -0.26, P = 0.006). During the length of follow-ups less than 12 weeks, mindfulness-based therapy significantly improved anxiety for follow-up <=12 weeks after the start of therapy, but not >12 weeks after the start of therapy.There was a lack of consistency between the studies in the type of mindfulness-based/control intervention implemented. Patients had different forms of cancer. Subgroup analyses included a relatively small number of studies and did not account for factors such as the severity of anxiety and/or depression, the time since diagnosis, and cancer stage.Mindfulness-based interventions effectively relieved anxiety and depression among patients with cancer. However, additional research is still warranted to determine how long the beneficial effects of mindfulness-based therapy persist. PMID- 26559247 TI - No Association of SERPINE1 -675 Polymorphism With Sepsis Susceptibility: A Meta Analysis. AB - The serine protease inhibitor clade E member 1 (SERPINE1) gene has been suggested to exert great influence on the development of sepsis. But there is little overlap in the results of association between SERPINE1 -675 4G/5G polymorphism and sepsis.To get a more precise estimation of this association, we conducted a meta-analysis with a relatively larger sample size including 1806 cases and 2239 controls. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between -675 4G/5G polymorphism and sepsis susceptibility. Subgroup analyses were conducted based on ethnicity and source of controls.The results showed that there was no association of the SERPINE1 polymorphism and sepsis susceptibility (5G5G vs 4G4G: OR = 0.87, CI = 0.75-1.03; 5G5G+4G5G vs 4G4G: OR = 0.93, CI = 0.84-1.02; 5G5G vs 4G4G+4G5G: OR = 0.96, CI = 0.83-1.11; 5G vs 4G: OR = 0.94, CI = 0.86-1.01; 4G5G vs 4G4G: OR = 0.90, CI = 0.80-1.01). Nor did any subgroup analysis indicate a significant association.In conclusion, -675 4G/5G polymorphism in the SERPINE1 gene may not be associated with the risk of sepsis. PMID- 26559248 TI - Red and Processed Meat Consumption Increases Risk for Non-Hodgkin Lymphoma: A PRISMA-Compliant Meta-Analysis of Observational Studies. AB - The association between consumption of red and processed meat and non-Hodgkin lymphoma (NHL) remains unclear. We performed a meta-analysis of the published observational studies to explore this relationship.We searched databases in MEDLINE and EMBASE to identify observational studies which evaluated the association between consumption of red and processed meat and risk of NHL. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects models were used to calculate summary relative risk (SRR) and the corresponding 95% confidence interval (CI).We identified a total of 16 case-control and 4 prospective cohort studies, including 15,189 subjects with NHL. The SRR of NHL comparing the highest and lowest categories were 1.32 (95% CI: 1.12-1.55) for red meat and 1.17 (95% CI: 1.07 1.29) for processed meat intake. Stratified analysis indicated that a statistically significant risk association between consumption of red and processed meat and NHL risk was observed in case-control studies, but not in cohort studies. The SRR was 1.11 (95% CI: 1.04-1.18) for per 100 g/day increment in red meat intake and 1.28 (95% CI: 1.08-1.53) for per 50 g/day increment in processed meat intake. There was evidence of a nonlinear association for intake of processed meat, but not for intake of red meat.Findings from our meta-analysis indicate that consumption of red and processed meat may be related to NHL risk. More prospective epidemiological studies that control for important confounders and focus on the NHL risk related with different levels of meat consumption are required to clarify this association. PMID- 26559249 TI - Antithrombotic Treatment for Recurrent Miscarriage: Bayesian Network Meta Analysis and Systematic Review. AB - Combined use of heparin and aspirin is frequently prescribed for treatment of recurrent miscarriage (RM) in patients with antiphospholipid syndrome (APS), or in those without apparent cause of RM other than thrombophilia; however, this strategy is largely based on expert opinion and has not been well studied. The option for the use of different antithrombotic therapies to improve live birth remains unclear. In this network meta-analysis, we incorporated direct and indirect evidence to evaluate effects of different antithrombotic treatments on prevention of pregnancy losses.We searched PubMed and Embase for randomized clinical trials comparing effects of at least 2 antithrombotic treatments on live birth in RM patients published from 1965 through the early of May 2015. Potential risk bias of eligible trials was evaluated according to the Cochrane Collaboration guidelines. Bayesian network meta-analysis was used to estimate relative effects on live birth.A total of 19 trials involving 2391 RM patients with or without thrombophilia and 543 with APS were included. No beneficial effect of antithrombotic treatment was observed either in RM patients with or without thrombophilia or in patients with APS; however, for patients with or without thrombophilia, low molecular weight heparin therapy had the greatest probability (61.48%) of being the best option in terms of live birth; for patients with APS, unfractionated heparin plus aspirin was the superior treatment for RM with the highest possibility (75.15%) of being top 2 places for reducing pregnancy losses. Aspirin was inferior in both groups.Our results do not support the use of combined low molecular weight heparin and aspirin for RM treatment, and suggested aspirin may have negative effects for lowering the risk of pregnancy loss. PMID- 26559250 TI - Enterohepatic Helicobacter Species as a Potential Causative Factor in Inflammatory Bowel Disease: A Meta-Analysis. AB - The Helicobacter species in the gut microbiota comprise Helicobacter pylori (H pylori) and enterohepatic Helicobacter species (EHS), which can colonize the intestinal mucosa. However, it is unclear whether EHS are associated with inflammatory bowel disease (IBD). Therefore, we conducted this meta-analysis to examine the association between EHS and IBD.PubMed, Scopus, Cochrane Library, and Web of Science databases, as well as abstracts from conference proceedings were searched to identify studies that used polymerase chain reaction to detect Helicobacter species in intestinal samples from patients with IBD.After screening, we carefully reviewed 20 of the 2955 identified studies, and performed a meta-analysis of the findings from 14 studies (11 adult studies and 3 pediatric studies) using STATA v12.0. These studies evaluated 1407 individuals, including 433 patients with Crohn's disease, 306 patients with ulcerative colitis, and 668 controls. The prevalence of Helicobacter species was higher among the patients with IBD, compared to that among the controls, which corresponded to a pooled risk ratio (RR) of 1.59 (95% confidence interval [CI]: 1.12-2.27). The RRs for adult and pediatric patients with IBD were 1.61 (95% CI: 1.03-2.52) and 1.76 (95% CI: 1.17-2.64), respectively. Compared to the controls, the patients with IBD tended to have a higher prevalence of EHS in the intestinal mucosa (RR: 2.01, 95% CI: 1.36-2.98), although the prevalence of H pylori was not significantly higher (RR: 1.22, 95% CI: 0.77-1.95). Compared to the controls, the RRs for EHS in patients with Crohn's disease and ulcerative colitis were 1.72 (95% CI: 1.20 2.47) and 3.27 (95% CI: 0.93-11.44), respectively.It appears that EHS was associated with IBD, while intestinal H pylori infection was not significantly associated with IBD. Further studies are needed to determine the involvement of EHS in the microbiological etiology of IBD. PMID- 26559251 TI - Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy. AB - It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3-4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan-Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03-3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08-2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy. PMID- 26559252 TI - Paradoxical Autoinflammatory Skin Reaction to Tumor Necrosis Factor Alpha Blockers Manifesting as Amicrobial Pustulosis of the Folds in Patients With Inflammatory Bowel Diseases. AB - The therapy of inflammatory bowel disease, particularly with tumor necrosis factor (TNF) blockers, may be associated with a number of cutaneous adverse effects, including psoriasis-like, eczema-like, and lichenoid eruptions. Other rare skin complications are neutrophilic dermatoses such as amicrobial pustulosis of the folds (APF), which is a chronic relapsing pustular disorder classified in this spectrum.The authors analyzed clinical, histopathologic, and cytokine expression profiles of 3 inflammatory bowel disease patients with APF triggered by adalimumab (patient 1) and infliximab (patients 2 and 3).All 3 patients presented with sterile pustules involving the cutaneous folds, genital regions, and scalp 6 months after starting adalimumab (patient 1) and 9 months after starting infliximab (patients 2 and 3). Histology was characterized by epidermal spongiform pustules with a dermal neutrophilic and lymphocytic infiltrate. Tumor necrosis factor blocker withdrawal associated with topical and systemic corticosteroids induced complete remission of APF in all 3 patients. The expressions of interleukin (IL)-1 beta and its receptors as well as TNF alpha and its receptors were significantly higher in APF than in controls. Also IL-17, leukocyte selectin, and chemokines, such as IL-8, [C-X-C motif] chemokine ligand 1/2/3 (C = cysteine, X = any amino acid), [C-X-C motif] chemokine ligand 16 (C = cysteine, X = any amino acid), and RANTES (regulated on activation, normal T cell expressed and secreted) were significantly overexpressed. Finally, the authors found significant overexpression of both metalloproteinases 2/9 and their inhibitors 1/2.The observation of 3 patients with APF following anti-TNF therapy expands not only the clinical context of APF but also the spectrum of anti-TNF side effects. Overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF is autoinflammatory in origin. PMID- 26559253 TI - Role of Endoglin Insertion and rs1800956 Polymorphisms in Intracranial Aneurysm Susceptibility: A Meta-Analysis. AB - Endoglin is an essential molecule during angiogenesis, vascular development, and integrity. Till now, many studies have investigated the association between endoglin polymorphisms and intracranial aneurysm (IA) risk, with the results remained inconclusive. Therefore, we performed a meta-analysis to summarize the possible association.We searched PubMed and Embase until June 2015 to identify studies addressing the association between endoglin polymorphisms and IA risk. The summary odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated to assess the strength of the association.Eleven studies with a total of 1501 cases and 2012 controls were finally included in this meta analysis, with 10 studies investigating endoglin 6-bp insertion (6bINS) polymorphism and 4 studies investigating 1800956 polymorphism. No significant association between endoglin 6bINS polymorphism and IA risk was detected in overall estimation (I/I vs wt/I + wt/wt: OR = 1.21, 95% CI = 0.87-1.69) or in the subgroup analysis by ethnicity, control source, or ruptured status. However, we observed an association with borderline significance of 6bINS with IA occurrence (I/I vs wt/I + wt/wt: OR = 1.49, 95% CI = 0.99-2.25, P = 0.058) in studies applying matched controls. Furthermore, we detected a significant association for 6bINS polymorphism of endoglin with increased risk of familial IA (I vs wt, OR = 1.64, 95% CI = 1.10-2.42) but not sporadic IA (I vs wt, OR = 1.09, 95% CI = 0.68 1.45). With regard to rs1800956, our pooled results indicated a significantly decreased IA risk in individuals carrying C allele (C/C vs G/C + G/G: OR = 0.65; 95% CI = 0.45-0.94).This meta-analysis provided no evidence for the association between 6bINS polymorphism with overall IA risk. However, we detected a significant association of 6bINS allele with increased risk of familial IA. Also, we found that rs1800956 was significantly related to IA occurrence. Further, well designed studies with large sample size are warranted and updated meta-analysis is needed to verify our findings. PMID- 26559254 TI - Tigecycline-induced Drug Fever and Leukemoid Reaction: A Case Report. AB - In this study, we describe a patient in whom tigecycline-induced drug fever and leukemoid reaction (LR) after 3 weeks of therapy for pneumonia.A 62-year-old man developed aspiration pneumonia on February 1, 2015. He had received multiple antibiotics at another hospital, but did not respond well. Disease rapidly progressed, and he was referred to our department on February 14. We adjusted the antibiotic therapy to tigecycline + vancomycin, and added voriconazole to empiric antifungal therapy. Pneumonia largely improved, and we discontinued vancomycin and voriconazole on February 28. With tigecycline monotherapy, his clinical status remained stable.On March 7, he developed high fever and LR (white blood cell count: 38.25 * 10(9)/L). Erythrocyte sedimentation rate and C-reactive protein were elevated, and CD8+ T cells had been abnormally activated. After a careful physical examination and laboratory investigation, we confirmed that primary infection did not progress and no other cause was evident. So we figured fever and LR might be induced by tigecycline. After discontinuing tigecycline and adding low-dose steroid, fever and LR totally resolved in 3 days, which further confirmed our diagnosis.According to this case and literature review, drug induced hypersensitivity should be considered in the differential diagnosis of fever and LR when the therapeutic duration of tetracycline approximates 3 weeks. Monitoring T-cell subsets may facilitate early diagnosis. When necessary, we should discontinue the suspected drug to confirm diagnosis. PMID- 26559255 TI - Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double Blind, and Placebo Controlled Clinical Trial. AB - Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [beta (95% confidence interval) = -0.88 (-1.62, -0.14) and P = 0.020 for low-FA; and beta (95% confidence interval) = -2.68 (-3.42, -1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001).The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage. PMID- 26559256 TI - Low Serum Levels of Uric Acid are Associated With Development of Poststroke Depression. AB - Poststroke depression (PSD) is a frequent complication of stroke that has been associated with poorer outcome of stroke patients. This study sought to examine the possible association between serum uric acid levels and the development of PSD.We recruited 196 patients with acute ischemic stroke and 100 healthy volunteers. Serum uric acid levels were tested by uricase-PAP method within 24 hr after admission. Neuropsychological evaluations were conducted at 3-month poststroke. The 17-item Hamilton Depression Scale was used to assess depressive symptoms. Diagnosis of PSD was made in accordance with DSM-IV criteria for depression. Multivariate analyses were conducted using logistic regression models.Fifty-six patients (28.6%) were diagnosed as having PSD at 3 months. PSD patients showed significantly lower levels of uric acid at baseline as compared to non-PSD patients (237.02 +/- 43.43 vs 309.10 +/- 67.44 MUmol/L, t = -8.86, P < 0.001). In multivariate analyses, uric acid levels (<=239.0 and >=328.1 MUmol/L) were independently associated with the development of PSD (OR, 7.76; 95% confidence interval [CI], 2.56-23.47, P < 0.001 and OR, 0.05; 95% CI, 0.01-0.43, P = 0.01, respectively) after adjustment for possible variables.Serum uric acid levels at admission are found to be correlated with PSD and may predict its development at 3 months after stroke. PMID- 26559257 TI - Left Ventricular Myxoma Leading to Stroke: A Rare Case Report. AB - Primary cardiac tumors are rare, and most are myxomas. Only approximately 5% of cardiac myxomas originate from the ventricles.We report the case of a 23-year-old man presenting with right hemiplegia and muscle strength degeneration under a diagnosis of stroke. Transthoracic echocardiography revealed a 29 * 26 mm mass arising from the anterior interventricular septum. The tumor was surgically removed, and histology confirmed the diagnosis of left ventricular myxoma.We report its clinical features and treatment to add to the current knowledge. PMID- 26559258 TI - Soluble Serum alphaKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma. AB - Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, alphaKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated alphaKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue alphaKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum alphaKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. alphaKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum alphaKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of alphaKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of alphaKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03).These results indicate that a decreased alphaKlotho expression is correlated with RCC progression, and suggest a key role of declining alphaKlotho in the onset of cancer metastasis. PMID- 26559259 TI - Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease: An Analysis of Linked Data. AB - To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD. PMID- 26559260 TI - Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single Center Retrospective Cohort Study. AB - Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 +/- 3.7% and 90-day overall survival after transplantation at 80.0 +/- 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (>=15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing HSCT. Patients with high-risk diseases with prolonged neutropenia and carbapenem-resistant GNB were independent risk factors for BSI-related mortality. PMID- 26559261 TI - Skin Autofluorescence and Mortality in Patients on Peritoneal Dialysis. AB - Skin autofluorescence (SAF) is a proven prognostic factor of mortality in hemodialysis patients. Traditional and nontraditional risk factors are almost equivalent in peritoneal dialysis (PD), and cardiovascular disease (CVD) is the leading cause of death. Moreover, peritoneal glucose absorption accelerates the degenerative processes of connective tissues as in diabetes. In our study, we examined the predictive value of SAF for total mortality in the PD population. Data were collected from 198 prevalently adult Caucasian PD patients. One hundred twenty-six patients (mean age 66.2 y, men [n = 73], diabetes ratio 75/126) had anamnestic CVD (coronary heart disease, cerebrovascular disease, peripheral arterial disease). Initially, we evaluated factors affecting SAF and CVD by multivariate linear regression. Survival rates were estimated by recording clinical and demographic data associated with mortality during a 36-month follow up using the Kaplan-Meier method. Analyses were further stratified based on the presence or absence of CVD and SAF levels above or below the upper tercile 3.61 arbitrary units.Skin autofluorescence was influenced by CVD (P < 0.01, 95% confidence interval [CI] 0.1-0.5) and white blood cell counts (P < 0.001, 95% CI 0.031-0.117). According to the Spearman correlation, SAF correlated with peritoneal cumulative glucose exposure (P = 0.02) and elapsed time in PD (P = 0.008). CVD correlated with age (P < 0.001, 95% CI 1.24-1.65) and diabetes (P < 0.001, 95% CI 2.58-10.66). More deaths were observed in the high SAF group than in the low SAF group (34/68 vs 44/130; P = 0.04). Comparing the CVD(-) low SAF group survival (mean 33.9 mos, standard error [SE] 1.39) to CVD(+) low SAF (mean 30.5 mos, SE 1.37, P = 0.03) and to CVD(+) high SAF group (mean 27.1 mos, SE 1.83, P = 0.001), the difference was significant.In conclusion, among PD patients, SAF values over 3.61 arbitrary units seem to be a predictor of mortality. The relationship among peritoneal glucose exposure, CVD, and diabetes suggests its suitability to characterize systemic cumulative glucose load in this patient population. PMID- 26559262 TI - Angioedema Related to Angiotensin-Converting Enzyme Inhibitors: Attack Severity, Treatment, and Hospital Admission in a Prospective Multicenter Study. AB - The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack.A prospective, multicenter, observational study (April 2012-December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission.Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5-1.0] versus 3.9 [2.5-7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1 INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5-1.3] versus 0.5 [0.4-1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3-28.2] and 5.9 [1.3 26.5], respectively). A favorable course was observed in all patients. Three patients (5%) experienced a recurrence after angiotensin-converting enzyme inhibitor discontinuation after a median follow-up of 18 (11-30) months.Two severity criteria-laryngeal edema and the progression of the edema-were independent factors associated with likelihood of hospital admission. Appropriate specific treatments (plasma-derived C1-INH or icatibant) should be available in EDs to prevent possibly life-threatening complications. PMID- 26559263 TI - Cytomegalovirus-Associated Gastroduodenal Ulcers in a Patient With Functional Hypercortisolism: A Case Report. AB - Cytomegalovirus (CMV)-associated gastroduodenal ulcers (GDU) are a rare digestive disease, which principally affect immunocompromised patients. We recently experienced CMV-associated GDU occurring in a seemingly immunocompetent patient. The rarity of such a condition was inimical to a correct clinical diagnosis.A 77 year-old woman with Alzheimer's disease was admitted to our hospital because of vomiting and anorexia. Her general condition was extremely poor due to severe dehydration. Any invasive procedures including gastroduodenal endoscopy could not be performed. Laboratory test results showed electrolyte imbalance, hyperglycemia, and hypercortisolemia. The plasma adrenocorticotropic hormone level was rather low. On her 11th day in hospital, she suddenly fell into shock status. Despite intensive care, the patient could not be rescued. An autopsy was performed and revealed that she had suffered from CMV-associated GDU and died of candidemia that invaded through the ulcer. Her adrenal glands showed neither neoplasm nor hyperplasia, suggesting that her hypercortisolism was a purely functional disorder. We concluded that the severe opportunistic infections were developed in association with functional hypercortisolism.This case suggests that functional hypercortisolism, even though transient, can cause a patient to be immunocompromised. PMID- 26559264 TI - Eosinophilic Granulomatosis With Polyangiitis With Thrombotic Microangiopathy: Is Simultaneous Systemic Lupus Erythematosus Associated With Clinical Manifestations?: A Case Report and Review of the Literature. AB - Eosinophilic granulomatosis with polyangiitis (EGPA) is one of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which is characterized by vasculitis of the small to medium-sized vessels. On the contrary, thrombotic microangiopathy (TMA) is a life-threatening condition which can cause ischemic organ injury. Although several case reports have described patients with TMA associated with ANCA-associated vasculitis except for EGPA, there are no previous case reports of EGPA associated with TMA.A 71-year-old Japanese man was diagnosed with EGPA based on his asthma, eosinophilia, lung opacity, refractory sinusitis, and positive myeloperoxidase-ANCA. He was also diagnosed with TMA based on peripheral schizocytes and hemolytic anemia. We performed plasmapheresis and started high-dose corticosteroid therapy; thereafter, he improved promptly. His case also fulfilled the classification criteria of systemic lupus erythematosus (SLE) based on the pleural effusion, renal disorder, anemia, thrombocytopenia, positive antidouble-stranded DNA antibody, and low complement. Elements of SLE were thought to affect his clinical course.We reviewed 11 patients with EGPA or hypereosinophilic syndrome (HES) associated with SLE, including our case. Patients with EGPA or HES associated with SLE had more heart complications than patients with simple EGPA or simple HES did. Patients with EGPA or HES associated with SLE had more pleural effusion than patients with simple SLE did.Clinical manifestations of eosinophilia with SLE or SLE with eosinophilia may differ from simple SLE or simple eosinophilia. PMID- 26559265 TI - Is Preoperative Biochemical Testing for Pheochromocytoma Necessary for All Adrenal Incidentalomas? AB - This study examined whether imaging phenotypes obtained from computed tomography (CT) can replace biochemical tests to exclude pheochromocytoma among adrenal incidentalomas (AIs) in the preoperative setting.We retrospectively reviewed the medical records of all patients (n = 251) who were admitted for operations and underwent adrenal-protocol CT for an incidentally discovered adrenal mass from January 2011 to December 2012. Various imaging phenotypes were assessed for their screening power for pheochromocytoma. Final diagnosis was confirmed by biopsy, biochemical tests, and follow-up CT.Pheochromocytomas showed similar imaging phenotypes as malignancies, but were significantly different from adenomas. Unenhanced attenuation values <=10 Hounsfield units (HU) showed the highest specificity (97%) for excluding pheochromocytoma as a single phenotype. A combination of size <=3 cm, unenhanced attenuation values <= 10 HU, and absence of suspicious morphology showed 100% specificity for excluding pheochromocytoma.Routine noncontrast CT can be used as a screening tool for pheochromocytoma by combining 3 imaging phenotypes: size <=3 cm, unenhanced attenuation values <=10 HU, and absence of suspicious morphology, and may substitute for biochemical testing in the preoperative setting. PMID- 26559266 TI - Surgical Versus Conservative Intervention for Acute Achilles Tendon Rupture: A PRISMA-Compliant Systematic Review of Overlapping Meta-Analyses. AB - Although many meta-analyses comparing surgical intervention with conservative treatment have been conducted for acute Achilles tendon rupture, discordant conclusions are shown. This study systematically reviewed the overlapping meta analyses relating to surgical versus conservative intervention of acute Achilles tendon rupture to assist decision makers select among conflicting meta-analyses, and to offer intervention recommendations based on the currently best evidence.Multiple databases were comprehensively searched for meta-analyses comparing surgical with conservative treatment of acute Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors independently evaluated the meta-analysis quality and extracted data. The Jadad decision algorithm was applied to ascertain which meta-analysis offered the best evidence.A total of 9 meta-analyses were included. Only RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 5 to 10 (median 7). A high-quality meta-analysis with more RCTs was selected according to the Jadad decision algorithm. This study found that when functional rehabilitation was used, conservative intervention was equal to surgical treatment regarding the incidence of rerupture, range of motion, calf circumference, and functional outcomes, while reducing the incidence of other complications. Where functional rehabilitation was not performed, conservative intervention could significantly increase rerupture rate.Conservative intervention may be preferred for acute Achilles tendon rupture at centers offering functional rehabilitation, because it shows a similar rerupture rate with a lower risk of other complications when compared with surgical treatment. However, surgical treatment should be considered at centers without functional rehabilitation as this can reduce the incidence of rerupture. PMID- 26559267 TI - 3D Image-Guided Percutaneous Radiofrequency Thermocoagulation of the Maxillary Branch of the Trigeminal Nerve Through Foramen Rotundum for the Treatment of Trigeminal Neuralgia. AB - Percutaneous radiofrequency thermocoagulation of the trigeminal ganglion through the foramen ovale is a well-established procedure for the treatment of trigeminal neuralgia (TN). However, this approach can be tricky when individual trigeminal sub-branch nerve block is required. We report our initial experience of image guided radiofrequency thermocoagulation of the maxillary branch through the use of foramen rotundum.From February 2012 to February 2015, we treated 25 patients with isolated TN of the maxillary branch. Radiofrequency thermocoagulation of the maxillary branch through the foramen rotundum was performed under fluoroscopy. TN pain was evaluated using the visual analogue scale both before and after the procedure.The mean preoperative visual analogue scale score was 8.6 +/- 0.8. The pain completely disappeared after the initial procedure in 22 patients and after a second procedure in 2 patients. An additional patient had a postoperative visual analogue scale score of 2 and did not undergo further treatment. Facial numbness occurred in 23 patients but was tolerable. Patients were followed up for a mean of 14.74 months (range, 1-29 months). Recurrence was observed in 9 patients (36%) during the follow-up period. All recurrences were well managed with repeat procedures.Percutaneous radiofrequency thermocoagulation of the maxillary branch through the foramen rotundum under fluoroscopy is a safe and effective procedure for the treatment of isolated TN of the maxillary branch. PMID- 26559268 TI - TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy. AB - Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade >=2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID- 26559269 TI - Randomized Clinical Trial Comparing Efficacy of Simo Decoction and Acupuncture or Chewing Gum Alone on Postoperative Ileus in Patients With Hepatocellular Carcinoma After Hepatectomy. AB - To compare the efficacy of simo decoction (SMD) combined with acupuncture at the tsusanli acupoint or chewing gum alone for treating postoperative ileus in patients with hepatocellular carcinoma (HCC) after hepatectomy.In postoperative ileus, a frequent complication following hepatectomy, bowel function recovery is delayed, which increases length of hospital stay. Studies suggest that chewing gum may reduce postoperative ileus; SMD and acupuncture at the tsusanli acupoint have long been used in China to promote bowel movement.Patients with primary HCC undergoing hepatectomy between January 2015 and August 2015 were randomized to receive SMD and acupuncture (n = 55) or chewing gum (n = 53) or no intervention (n = 54) starting on postoperative day 1 and continuing for 6 consecutive days or until flatus. Primary endpoints were occurrence of postoperative ileus and length of hospital stay; secondary endpoints were surgical complications.Groups treated with SMD and acupuncture or with chewing gum experienced significantly shorter time to first peristalsis, flatus, and defecation than the no-intervention group (all P < 0.05). Hospital stay was significantly shorter in the combined SMD and acupuncture group (mean 14.0 d, SD 4.9) than in the no-intervention group (mean 16.5 d, SD 6.8; P = 0.014), while length of stay was similar between the chewing gum group (mean 14.7, SD 6.2) and the no-intervention group (P = 0.147). Incidence of grades I and II complications was slightly lower in both intervention groups than in the no-intervention group.The combination of SMD and acupuncture may reduce incidence of postoperative ileus and shorten hospital stay in HCC patients after hepatectomy. Chewing gum may also reduce incidence of ileus but does not appear to affect hospital stay. (Clinicaltrials.gov registration number: NCT02438436.). PMID- 26559270 TI - Antifungal Treatment is Not Required for Immunocompetent Individuals With Asymptomatic Esophageal Candidiasis. AB - Although esophageal candidiasis (EC) is an opportunistic infection, asymptomatic EC (AEC) is occasionally encountered in otherwise healthy individuals. This study evaluates the impact of antifungal treatment in immunocompetent individuals with AEC and investigates risk factors for persistent or recurrent EC. The authors identified patients with biopsy-proven AEC from the database of individuals receiving screening endoscopy (n = 99,255). After excluding patients receiving immunosuppressive therapy, being positive for human immunodeficiency virus, receiving no follow-up endoscopy, or having no antifungal treatment data, a total of 142 patients were divided into remission and nonremission groups. Remission was defined when EC was not detectable on follow-up endoscopy. On baseline comparison, nonremission group was older (57.5 +/- 10.3 versus 52.5 +/- 10.5 years, P = 0.017) and more likely to have cardiovascular disease (12.9% versus 1.8%, P = 0.021) and history of pulmonary tuberculosis (PTB) (22.6% versus 4.5%, P = 0.004) and exhibited a lower triglyceride level (101.4 +/- 37.4 versus 122.6 +/- 79.6 mg/dL, P = 0.039) than remission group, whereas grade of EC and concomitant endoscopic findings did not differ between 2 groups. Antifungal treatment was also similarly performed between 2 groups. Multivariate analysis revealed that history of PTB is independently associated with nonremission (odds ratio 4.495, 95% confidence interval 1.023-19.762, P = 0.047). No patients demonstrated EC-related complications during a mean follow-up of 28.0 +/- 12.0 months. In conclusion, our results suggested that antifungal treatment is not required for immunocompetent individuals with AEC and past history of PTB is an independent predictor for persistent or recurrent EC. PMID- 26559271 TI - Clinicopathologic Features of Gastric Schwannoma: 8-Year Experience at a Single Institution in China. AB - To explore the clinicopathologic characteristics, diagnosis, treatment, and prognosis of gastric schwannoma in the imatinib era.The clinicopathologic characteristics and postoperative outcomes of patients diagnosed with gastric schwannoma at our institution between January 2007 and February 2015 were retrospectively collected and analyzed.The main patient complaint was epigastric pain or discomfort. Tumor sizes ranged from 15 to 80 mm (mean, 57.1 mm). In 17 patients, the tumors were located in the body of the stomach. A total of 20 patients were preoperatively misdiagnosed with a gastrointestinal stromal tumor. The rate of correct preoperative diagnosis was only 3.3%. All patients underwent surgical resection and showed strong S-100 protein positivity. Laparoscopic surgery for gastric schwannoma was associated with less blood loss and a shorter postoperative hospital stay than open surgery (P < 0.01). Total 28 patients were disease free without recurrence or metastasis at a median follow-up time of 50 months.Gastric schwannoma is often preoperatively misdiagnosed as gastric gastrointestinal stromal tumor. Laparoscopic resection of gastric schwannoma is considered safe and effective, and it may be the preferred surgery for most small and moderate-sized tumors. The long-term outcome is excellent, as this type of neoplasm is uniformly benign. PMID- 26559272 TI - Predictors of Pathologic Complete Response in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation. AB - Preoperative chemoradiotherapy (CRT) is the standard of care for patients with stage II and III rectal cancer. This strategy leads to pathologic complete response (pCR) in a significant number of patients. Factors predictive of pCR are currently being extensively investigated. The aim of this study was to analyze clinical factors that might be predictive of pCR.This study was a retrospective analysis of rectal cancer patients from January 2004 through December 2012. A total of 332 stage II and III patients with middle and low rectal cancer (<=10 cm) who received CRT and underwent curative total mesorectal excision were eligible. The median radiation dose was 50.4 Gy, and 72.6% of patients received infusional 5-fluorouracil with leucovorin, whereas 19.6% of patients received TS 1 with irinotecan, and 7.8% of patients received xeloda only. Pathologic complete response was confirmed by using pathologic specimens and analyzed based on predictive clinical factors.Among the 332 patients, 27.4% (n = 91) achieved pCR. Age, sex, body mass index, clinical T and N stages, tumor differentiation, the chemotherapy agent for CRT, and the time interval between CRT and surgery did not differ between the pCR and non-pCR groups. Carcinoembryogenic antigen (CEA) levels before CRT were 4.61 +/- 7.38 ng/mL in the pCR group and 10.49 +/- 23.83 ng/mL in the non-pCR group (P = 0.035). Post-CRT CEA levels were 1.4 +/- 1.07 ng/mL in the pCR group and 2.16 +/- 2.8 ng/mL in the non-pCR group (P = 0.014), and the proportion of middle rectal cancer patients was higher in pCR group (54.9%, P = 0.028). The results from multivariate logistic regression analysis indicated that higher tumor location (odds ratio 2.151; P = 0.003) and low post CRT CEA level (odds ratio 0.789; P = 0.04) were independent predictive factors for pCR.Tumor location and post-CRT CEA level were predictive factors in pCR for rectal cancer patients. Therefore, these factors may be important determinants in achieving pCR, and may also be used to predict oncologic outcomes. PMID- 26559273 TI - Identification of Poor-outcome Biliopancreatic Carcinoma Patients With Two-marker Signature Based on ATF6alpha and p-p38 "STARD Compliant". AB - Biliopancreatic cancer is one of the most aggressive solid neoplasms, and incidence is rising worldwide. It is known that ATF6alpha is one of the transmembrane proteins that acts crucially in endoplasmic reticulum stress response, and knockdown induces apoptosis of pancreatic cells. Apart from this, p p38 has been previously correlated with better outcome in pancreatic cancer. Interestingly, ATF6alpha knockdown pancreatic cells showed increased p-p38. The aim of this study was to evaluate the expression of these 2 proteins, p-p38 and ATF6alpha, and their correlation with the outcome of biliopancreatic adenocarcinoma patients. Samples from patients with biliopancreatic adenocarcinoma that underwent pancreaticoduodenectomy from 2007 to 2013 were used to construct a tissue microarray to evaluate p-p38 and ATF6alpha proteins by immunohistochemistry. We observed that both markers showed a tendency to impact in the time to recurrence; then a combination of these 2 proteins was analyzed. Combination of ATF6alpha(high) and p-p38(low) was strongly associated with a higher risk of recurrence (hazard ratio 2.918, P = 0.013). This 2-protein model remained significant after multivariate adjustment.We proposed a 2-protein signature based on ATF6alpha(high) and p-p38(low) as a potential biomarker of risk of recurrence in resected biliopancreatic adenocarcinoma patients. PMID- 26559274 TI - Microcystic/Reticular Schwannoma of the Mandible First Case Report and Review of the Literature. AB - Schwannoma comprises a group of nerve sheath tumors. Morphologic variants of schwannoma have no distinct relationship to clinical behavior, but unawareness of rare variants may lead to diagnostic pitfall and risk of mistreatment. Microcystic/reticular schwannoma is a recently described rare variant of schwannoma. We report a case of a 61-year-old female with a 5.0 cm * 3.5 cm * 3.0 cm mass in the right mandible, which has never been reported to date. Light microscopic evaluation showed that the mass was circumscribed with focal infiltration. Arranged in a prominent microcystic and reticular growth pattern, tumor cells were spindle-shaped with eosinophilic cytoplasm. No evidence of cytologic atypia, mitosis, or necrosis was observed. The stroma of the tumor mainly contained myxoid material with local infiltration of hyalinized collagen. Tumor cells showed diffuse and strong nuclear and cytoplasmic immunoreactivity for S100 protein. Tumor cells were also positive for CD34, CD99, and NSE, but negative for CK, EMA, CK5/6, P63, Calponin, CD10, SMA, Desmin, GFAP, NF, Syn, and CgA. The proliferation marker MIB-1 showed <1% nuclear reaction. Furthermore, we reviewed the clinical and pathological features of 24 previously reported cases of microcystic/reticular schwannoma. Unlike classic schwannoma, the reticular variant showed striking microcystic and reticular architecture microscopically. Recognition of these distinct entities is essential in avoiding misdiagnosis. Unlike classic schwannoma with a complete capsule, some masses were reported to lack encapsulation or contain focal infiltration. Further follow-up of tentative or identified cases is necessary to better understand this schwannoma. PMID- 26559275 TI - Comparative Short-Term Clinical Outcomes of Mediastinum Tumor Excision Performed by Conventional VATS and Single-Port VATS: Is It Worthwhile? AB - Single-port video-assisted thoracoscopic surgery (VATS) has been widely applied recently. However, there are still only few reports describing its use in mediastinum tumor resection. We present the technique of single-port video assisted thoracoscopic mediastinum tumor resection and compare it with conventional VATS with regard to short-term outcome.We retrospectively enrolled 105 patients who received mediastinum surgery in Chang Gung Memorial Hospital. Sixteen patients received sternotomy or thoracotomy, 29 patients received single port VATS, and 60 patients received conventional VATS (3 ports). The operative time, blood loss, postoperation day 1 pain score, discharge day pain score, and postoperative hospital stay were compared. In order to establish a well balanced cohort study, we also use propensity scores match (1:1) to compare the short-term clinical outcome in 2 groups.No operative deaths occurred in this study. Single port VATS was associated with shorter operative time, lower postoperation day 1 pain score, and shorter postoperation hospital stay in our cohort study (P = 0.001, <0.001, and 0.039), and propensity scores matched cohort study (P = 0.003, <0.001, and <0.001).Single-port VATS for mediastinum tumor appears to be a safe and promising technique with short-term outcome not inferior to conventional VATS in our cohort study. The long-term oncology outcome may require time and more enrolled patients to be further evaluated. PMID- 26559276 TI - Prevalence of Myopia in France: A Cross-Sectional Analysis. AB - Refractive error (RE), particularly myopia, is the first cause of visual impairment throughout the world. This study aimed to depict the prevalence of myopia in a multicentric series of French individuals.This cross-sectional analysis was carried out between January 2012 and November 2013 in eye clinics dedicated to REs. Data collection included age, gender, best-corrected visual acuity, RE, and any relevant medical history involving laser refractive surgery and cataract surgery. Exclusion criteria consisted of monophthalm patients or those with incomplete demographic data.Prevalences in the overall population, by gender and by age groups were reported for mild myopia (-0.50 to -2.75 diopter [D]), moderate myopia (-3 to -5.75 D), high myopia (less than -6 D), and very high myopia (less than -10 D).The analysis included 100,429 individuals, mean age 38.5 years (+/- 16.9). Overall prevalence of myopia was 39.1% (95% CI 38.8-39.4). Prevalences of mild, moderate, high and very high myopia were respectively 25.1% (95% CI 25.4-24.9), 10.6% (95% CI 10.4-10.8), 3.4% (95% CI 3.3-3.5) and 0.5% (95% CI 0.48-0.57).Even if possible bias occurred in recruitment, our results are similar to RE data collected in nationally representative samples of Caucasians in other studies. This is to our knowledge, one of the largest European series of individuals dedicated to myopia prevalences in different age groups. These results confirm the importance of myopia as a major health issue in Western countries. PMID- 26559277 TI - Cortical Activation During Levitation and Tentacular Movements of Corticobasal Syndrome. AB - Levitation and tentacular movements (LTM) are considered specific, yet rare (30%), features of Corticobasal Syndrome (CBS), and are erroneously classified as alien hand. Our study focuses on these typical involuntary movements and aims to highlight possible neural correlates.LTM were recognizable during functional magnetic resonance imaging (fMRI) in 4 of 19 CBS patients. FMRI activity was evaluated with an activation recognition program for movements, during LTM, consisting of levitaton and finger writhing, and compared with the absence of movement (rest) and voluntary movements (VM), similar to LTM, of affected and unaffected arm-hand. FMRI acquisition blocks were balanced in order to match LTM blocks with rest and VM conditions. In 1 of the 4 patients, fMRI was acquired only during LTM and with a different equipment.Despite variable intensity and range of involuntary movements, evidenced by videos, fMRI showed, during LTM, a significant (P<0.05-0.001) activation only of the contralateral primary motor cortex (M1). Voluntary movements of the affected and unaffected arm elicited the known network including frontal, supplementary, sensory-motor cortex, and cerebellum. Willed movements of the LTM-affected arm induced higher and wider activation of contralateral M1 compared with the unaffected arm.The isolated activation of M1 suggests that LTM is a cortical disinhibition symptom, not involving a network. Higher activation of M1 during VM confirms that M1 excitability changes occur in CBS. Our study calls, finally, attention to the necessity to separate LTM from other alien hand phenomena. PMID- 26559278 TI - Spontaneous Intra-Abdominal Hemorrhage Due to Rupture of Jejunal Artery Aneurysm in Behcet Disease: Case Report and Literature Review. AB - Rupture of jejunal artery aneurysm is a very rare event resulting in life threatening hemorrhage in Behcet disease (BD). We report a case of ruptured jejunal artery aneurysm in a 35-year-old patient with BD. The patient had a 1 year history of intermittent abdominal pain caused by superior mesenteric artery aneurysm with thrombosis. Anticoagulation treatment showed a good response. Past surgical history included stenting for aortic pseudoaneurysm. On admission, the patient underwent an urgent operation due to sudden hemorrhagic shock. Resection was performed for jejunal artery aneurysm and partial ischemia of intestine. The patient was diagnosed with BD, based on a history of recurrent oral and skin lesions over the past 6 years. Treatment with anti-inflammatory medications showed a good response during the 8-month follow-up.An increased awareness of BD and its vascular complications is essential. Aneurysms in BD involving jejunal artery are rare, neglected and require proper management to prevent rupture and death. To our knowledge, this is the first reported case of jejunal artery aneurysm caused by BD. PMID- 26559279 TI - Maternal Blood Pressure During Pregnancy and Early Childhood Blood Pressures in the Offspring: The GUSTO Birth Cohort Study. AB - Although epidemiological studies suggest that offspring of women with preeclampsia are at increased risk to higher blood pressures and cardiovascular disease, little is known about the nature of blood pressures between the mother and her offspring. As blood pressures comprise of both pulsatile (systolic blood pressure [SBP] and pulse pressure [PP]) and stable (diastolic blood pressure [DBP]) components, and they differ between central and peripheral sites, we sought to examine maternal peripheral and central blood pressure components in relation to offspring early childhood blood pressures. A prospective birth cohort of 567 Chinese, Malay, and Indian mother-offspring with complete blood pressure information were studied. Maternal brachial artery SBP, DBP, and PP were measured at 26 to 28 weeks gestation; and central SBP and PP were estimated from radial artery waveforms. Offspring brachial artery SBP, DBP, and PP were measured at 3 years of age. Associations between continuous variables of maternal blood pressures (peripheral SBP, DBP, PP, central SBP, and PP) and offspring blood pressures (peripheral SBP, DBP, and PP) were examined using multiple linear regression with adjustment for maternal characteristics (age, education level, parity, smoking status, alcohol consumption and physical activity during pregnancy, and pre-pregnancy BMI) and offspring characteristics (sex, ethnicity, BMI, and height at 3 years of age). In the multivariate models, offspring peripheral SBP increased by 0.08 (95% confidence interval 0.00-0.17, P = 0.06) mmHg with every 1-mmHg increase in maternal central SBP, and offspring peripheral PP increased by 0.10 (0.01-0.18, P = 0.03) mmHg for every 1-mmHg increase in maternal central PP. The relations of maternal-offspring peripheral blood pressures (SBP, DBP, and PP) were positive but not statistically significant, and the corresponding values were 0.05 (-0.03 to 0.13; P = 0.21), 0.03 (-0.04 to 0.10; P = 0.35), and 0.05 (-0.02 to 0.13; P = 0.14), respectively. Maternal central pulsatile blood pressure components (SBP and PP) during pregnancy are associated with higher blood pressures in the offspring. This positive correlation is already evident at 3-years old. Studies are needed to further evaluate the effects of maternal central pulsatile blood pressure components during pregnancy and long-term cardiovascular health in the offspring. PMID- 26559280 TI - Dementia Risk in Irradiated Patients With Head and Neck Cancer. AB - Patients with head and neck cancer are treated through surgery, radiotherapy (RT), and chemotherapy (CT). Carotid artery damage and neurotoxicity were previously observed in these patients. This study estimated the dementia risk associated with different treatment modalities in a head and neck cancer population with long-term follow-up. Taiwan's National Health Insurance claims database and a cancer registry database from the Collaboration Center of Health Information Application were linked for the present analysis. Patients with head and neck cancer, treated from January 1, 2002 to December 31, 2010, were included in the study. The follow-up duration was the period from the index date to December 31, 2012. Inclusion criteria were head and neck cancer; an age >20 years; and having undergone surgery, CT, concurrent CT, or surgery with adjuvant treatment. Exclusion criteria were another cancer diagnosed before the head and neck cancer, death or being diagnosed with dementia within 2 years after the treatment of the head and neck cancer, stroke before the index date, distant metastasis, in situ carcinoma, sarcoma, head and neck cancer recurrence, an unknown sex, and an age <20 years. In total, 20,135 patients were included. In patient groups that underwent surgery alone, surgery and adjuvant chemoradiotherapy, and chemoradiotherapy alone, the dementia incidence per 1000 person-years was 1.44, 1.04, and 1.98, respectively. The crude hazard ratio (HR) of dementia was 1.84 (95% confidence interval [CI] 1.21-2.81) in the RT with or without CT group. After adjustment for age, sex, clinical stage, and comorbidity, the HR was 1.92 (95% CI 1.14-3.24). Examining the dementia risk in patients who received different treatment modalities according to the Cox proportional-hazard model revealed that an age >65 years and having undergone RT with or without CT were risk factors (P < 0.001 and P = 0.015; and HRs of 16.5 and 1.92, respectively). The dementia risk in patients at different clinical stages was not significantly different among the various treatment groups, regardless of whether the patients received RT. However, younger (<65 y) patients who received RT with or without CT had a 2.96-fold (95% CI 1.24-7.08) higher risk of dementia and a 3.54-fold (95% CI 1.32-9.51) higher adjusted HR compared with the surgery-alone group. Patients who received a total radiation dose >6660 cGy exhibited a 1.69 fold (95% CI 0.97-2.95, P = 0.063) higher dementia risk compared with those who received a total radiation dose <6660 cGy. Receiving a higher radiation dose increased the dementia risk and persistently escalated the dementia incidence even 9 years after RT. Younger (<65 y) patients have a high risk of dementia after RT. The selection of young patients for dose de-escalation requires improvement for reducing irradiation to the neck and areas near brain tissues, particularly in Taiwan, where the median patient age is 53 years. PMID- 26559281 TI - Protective Effect of Surgery Against Early Subtalar Arthrodesis in Displaced Intra-articular Calcaneal Fractures: A Meta-Analysis. AB - The aim of this study is to determine whether surgery offers protection against early subtalar arthrodesis in displaced intraarticular calcaneal fractures. Systematic review and meta-analysis: searches of electronic databases 1980 to August 2014, checking of reference lists, hand searching of journals, and contact with experts. Randomized controlled trials (RCTs) in which surgical treatment was compared with nonsurgical treatment of displaced intra-articular calcaneal fractures from 1980 to 2014. The modified Jadad scale was used for trial quality and effective data were pooled for meta-analysis. Study results related to early subtalar arthrodesis were extracted and risk assessment was combined with surgical treatment and nonsurgical treatment. The primary analysis included 4 studies and 966 participants. The estimated overall risk ratio was 4.40 (95% confidence interval 2.67-7.39), indicating the incidence of early subtalar arthrodesis in nonsurgical group is 4.4 times the surgical group. The results showed that surgical treatment was superior to nonsurgical treatment in protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures (Z = 5.600, P < 0.001).Surgery offers protection against early subtalar arthrodesis in displaced intra-articular calcaneal fractures. PMID- 26559282 TI - Classification and Morphological Parameters of the Scapular Spine: Implications for Surgery. AB - Incidence of scapular spine (SS) fractures as a result of complications of reverse total shoulder arthroplasty is relatively high leading to inferior clinical outcomes and an increased risk of revision and dislocation. Fractures of SS because of trauma, including the acromion, constitute 6% to 23% of scapula fractures. The purpose of this study was to classify the SS and present specific geometrical parameters according to osteologic features. A total of 319 intact dry scapulae were collected and classified based on morphological characteristics and shape of the SS. Nine bony landmarks were also chosen and described for their relevance to regions of interest for scapular fixation. Five specific types of SS were noted and the most prevalent groups were Type 1 (Fusiform shape) (47.17%) and Type 5 (Horizontal S-shape) (19.18%). Overall, Types 3, 4, and 1 showed thicker landmark values compared to Type 5, with Type 2 having smaller values. Our classification into 5 distinct types allowed appreciation of the anatomical variance of SSs. The contours of Types 5 and 1 presented a more complex morphology and may lead to a worse surgical approach due to a fracture. As Types 2 and 5 were much thinner than the other types, these may be more susceptible to fractures. PMID- 26559283 TI - Preoperative Intra-abdominal Sepsis, Not Penetrating Behavior Itself, Is Associated With Worse Postoperative Outcome After Bowel Resection for Crohn Disease: A Retrospective Cohort Study. AB - It is generally believed that penetrating behavior is associated with worse surgical outcomes in Crohn disease (CD). We hypothesized that intra-abdominal sepsis (IAS), but not penetrating behavior itself, contributes to postoperative morbidity in patients undergoing bowel resection for CD.Patients who underwent surgery from April 2010 to April 2014 were retrospectively identified from a prospectively maintained database. Demographic information and preoperative and operative data were collected. The outcomes following surgery in patients who had penetrating disease with or without IAS versus nonpenetrating CD were compared.Of 288 patients, 180 had penetrating CD, including 54 who had IAS. Preoperative characteristics were similar between the groups, except for serum albumin, abdominal drainage, and prior bowel resection. Patients with penetrating CD with IAS were more likely to have a stoma, surgical site complications, postoperative IAS complications, and major complications than patients with penetrating CD without IAS or nonpenetrating CD. There were no significant differences between patients with penetrating CD without IAS and nonpenetrating CD. The postoperative outcome was strengthened after propensity-score matching analysis. Moreover, penetrating CD with IAS (odds ratio [OR], 13.034; P = 0.004) is a risk predictor for major postoperative complications, and preoperative serum albumin (OR, 0.095; P = 0.002) and preoperative enteral nutrition (OR, 0.203, P = 0.049) are protective.Penetrating CD without IAS did not adversely affect postoperative outcome after bowel resection compared with penetrating CD with IAS. These results may revise the notion that all patients with penetrating CD have worse postoperative complications. PMID- 26559284 TI - Metabolomic Analysis of Plasma From Patients With Acute Mountain Sickness Using Chromatography-Mass Spectrometry. AB - Although acute mountain sickness (AMS) has long been recognized, little is known about this condition to date. The current study was conducted to explore changes in the metabolomic profiles of AMS patients and to further assess the potential of using these changes for the diagnosis of AMS. Plasma samples from 12 patients with AMS and 12 individuals without AMS were collected and used for further bioinformatics analysis by gas chromatography-mass spectrometry (GC-MS). The following analytical methods were used: gas chromatography-mass spectrometry data preprocessing, principal components analysis, partial least squares-discriminant analysis, model validation, orthogonal partial least squares-discriminant analysis, and the screening and identification of differences in metabolites. The results revealed a significantly difference between the subjects with AMS and those in the control group. Compared with plasma from the controls, plasma from the AMS patients contained significantly increased hypoxanthine, cysteinylglycine, D-arabitol, L-allothreonine, 2-ketobutyric acid, and succinate semialdehyde. The identification of metabolomic changes may be useful for the diagnosis of AMS in the future and may lay the foundation for further study of AMS pathogenesis. PMID- 26559285 TI - Strategies to Screen for Diabetic Retinopathy in Chinese Patients with Newly Diagnosed Type 2 Diabetes: A Cost-Effectiveness Analysis. AB - To investigate the cost-effectiveness of different screening intervals for diabetic retinopathy (DR) in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Chinese healthcare system.Chinese general clinical setting. A cost-effectiveness model was developed to simulate the disease course of Chinese population with newly diagnosed with diabetes. Different DR screening programs were modeled to project economic outcomes. To develop the economic model, we calibrated the progression rates of DR that fit Chinese epidemiologic data derived from the published literature. Costs were estimated from the perspective of the Chinese healthcare system, and the analysis was run over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. Total costs, vision outcomes, costs per quality-adjusted life year (QALY), the incremental cost-effectiveness ratio (ICER) of screening strategies compared to no screening. DR screening is effective in Chinese patients with newly diagnosed T2DM, and screen strategies with >=4-year intervals were cost-effective (ICER <$7,485 per QALY) compared to no screening. Screening every 4 years produced the greatest increase in QALYs (11.066) among the cost-effective strategies. The screening intervals could be varied dramatically by age at T2DM diagnosis. Probabilistic sensitivity analyses demonstrated the consistency and robustness of the cost-effectiveness of the 4-year interval screening strategy. The findings suggest that a 4-year interval screening strategy is likely to be more cost effective than screening every 1 to 3 years in comparison with no screening in the Chinese setting. The screening intervals might be tailored according to the age at T2DM diagnosis. PMID- 26559286 TI - Anthropometric Assessment of Neck Adipose Tissue and Airway Volume Using Multidetector Computed Tomography: An Imaging Approach and Association With Overall Mortality. AB - Neck adiposity tissue volume (NATV) accumulation is an indicator for metabolic syndrome and cardiovascular disease (CVD). Neck circumference is a poor measure of NATV, and a quantifier for this entity has not yet been established. To evaluate volumetric quantification by multidetector computed tomography (MDCT) as a reproducible anthropometric tool to measure NATV and airway volume (AWV). A total of 519 patients, including a subset of 70 random patients who underwent head and neck CT scanning in our hospital within 1 year (2013), were studied. Included patients were all those undergoing nonenhanced CT (NECT) or CT angiography (CTA). Neck cross-sectional areas (NCSA) were measured at 2 separate levels of the neck, and 3D postprocessing tissue reconstruction was performed, and NATV and AWVs were quantified volumetrically for all patients within the year. The average NCSA at the level of the soft palate and thyroid cartilage was 22,579 and 14,500 mm, respectively. NATV when compared to the upper and lower levels of NCSA showed correlations of 0.64 and 0.79, respectively (P < 0.001). Interobserver analysis showed mean deviations of 0.46% and 0.32% for NATV and AWV, respectively. A strong correlation between NATV and body mass index (BMI) was found (r = 0.658, P < 0.001), and the top quartile of NATV:AWV patients (out of 519 patients) displayed a statistically significant mortality rate during 670 days of follow-up (d = 7.5%, P = 0.032). After adjustment for age and gender, the association between NATV:AWV and mortality was close to significant (P = 0.072). Volumetric quantification of NATV and AWV is a reproducible and prognostic anthropometric tool, as a high NATV:AWV demonstrated a significant risk factor for mortality; future research may further advance our understanding of this phenomenon. PMID- 26559287 TI - Hematological Parameters Improve Prediction of Mortality and Secondary Adverse Events in Coronary Angiography Patients: A Longitudinal Cohort Study. AB - Prediction of primary cardiovascular events has been thoroughly investigated since the landmark Framingham risk score was introduced. However, prediction of secondary events after initial events of coronary artery disease (CAD) poses a new challenge. In a cohort of coronary angiography patients (n = 1760), we examined readily available hematological parameters from the UPOD (Utrecht Patient Oriented Database) and their addition to prediction of secondary cardiovascular events. Backward stepwise multivariable Cox regression analysis was used to test their ability to predict death and major adverse cardiovascular events (MACE). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) measures were calculated for the hematological parameters on top of traditional risk factors to assess prediction improvement. Panels of 3 to 8 hematological parameters significantly improved prediction of death and adverse events. The IDIs ranged from 0.02 to 0.07 (all P < 0.001) among outcome measures and the cNRIs from 0.11 to 0.40 (P < 0.001 in 5 of 6 outcome measures). In the hematological panels red cell distribution width (RDW) appeared most often. The multivariable adjusted hazard ratio of RDW per 1 standard deviation (SD) increase for MACE was 1.19 [1.08-1.32], P < 0.001. Routinely measured hematological parameters significantly improved prediction of mortality and adverse events in coronary angiography patients. Accurately indicating high risk patients is of paramount importance in clinical decision-making. PMID- 26559288 TI - The Long-Term Effective Rate of Different Branches of Idiopathic Trigeminal Neuralgia After Single Radiofrequency Thermocoagulation: A Cohort Study. AB - To evaluate the efficacy of computed tomography (CT) guided single radiofrequency thermocoagualtion (RFT) in 1137 patients with idiopathic trigeminal neuralgia after a follow-up period of 11 years, specially focused on duration of pain relief in different branches of trigeminal nerve, side effect, and complications. Retrospective study of patients with idiopathic trigeminal neuralgia treated with a single CT guided RFT procedure between January 2002 and December 2013. The mean follow-up time was 46.14 +/- 30.91 months. Immediate postprocedure pain relief was 98.4%. V2 division obtained the best pain relief rate: 91%, 89%, 80%, 72%, 60%, and 54% at 1, 3, 5, 7, 9, and 11 years, respectively. No statistical difference pairwise comparison was in other groups. The complications included masseter muscle weakness, corneitis, diplopia, ptosis, hearing loss, limited mouth opening, and low pressure headache. Masticatory weakness mostly occurred in patients with V3 branch involvement, while Corneitis and Diplopia all in patients with V1 branch involvement. No mortalities observed during or after RFT. All different branches division of trigeminal neuralgia achieved comparable satisfactory curative effect; V2 obtained the best excellent pain relief, after RFT procedure. Facial numbness is inevitable after RFT, which patients who have pain in all 3 trigeminal divisions and patients who desire no facial numbness should be cautious. Masticatory weakness is mainly related with V3 injured, while Corneitis and Diplopia in patients with V1 injured by RFT. PMID- 26559289 TI - Sagittal Balance in Adolescent Idiopathic Scoliosis: A Radiographic Study of Spinopelvic Compensation After Selective Posterior Fusion of Thoracolumbar/Lumbar (Lenke 5C) Curves. AB - The relationship between spinal sagittal alignment and pelvic parameters is well known in adolescent idiopathic scoliosis. However, few studies have reported the sagittal spinopelvic relationship after selective posterior fusion of thoracolumbar/lumbar (TL/L) curves. We evaluated the relationship between spinal sagittal alignment and the pelvis, and analyzed how the pelvic sagittal state is adjusted in Lenke type 5C patients. We conducted a retrospective study of 36 patients with Lenke type 5C curves who received selective posterior TL/L curve fusion. Coronal and spinopelvic sagittal parameters were pre and postoperatively compared. Pearson coefficients were used to analyze the correlation between all spinopelvic sagittal parameters before and after surgery. We also evaluated 3 pelvic morphologies (anteverted, normal, and retroverted) before and after surgery. Preoperatively, the mean pelvic incidence was 46.0 degrees , with a pelvic tilt and sacral slope (SS) of 8.2 degrees and 37.8 degrees , respectively, and 25% (9/36) of patients had an anteverted pelvis, whereas the other 75% had a normal pelvis. Postoperatively, 42% (15/36) of patients had a retroverted pelvis, 53% (19/36) had a normal pelvis, and 2 patients had an anteverted pelvis. Logistic regression analyses yielded 2 factors that were significantly associated with the risk for a postoperative unrecovered anteverted pelvis, including increased lumbar lordosis (LL) (odds ratio [OR] 4.8, P = 0.029) and increased SS (OR 5.6, P = 0.018). Four factors were significantly associated with the risk of a postoperative newly anteverted pelvis, including LL at the final follow-up (OR 6.9, P = 0.009), increased LL (OR 8.9, P = 0.003), LL below fusion (OR 9.4, P = 0.002), and increased SS (OR 11.5, P = 0.001). The pelvic state may be adjusted after selective posterior TL/L curve fusion in Lenke 5C adolescent idiopathic scoliosis patients. It is difficult to improve an anteverted pelvis in patients who have an LL that is increased by more than 11.6 degrees or an SS that is increased by more than 4.7 degrees after surgery. The anteverted pelvic state will generally occur with posterior correction surgery for patients with an LL that is greater than 63.7 degrees , or an LL or SS that is respectively increased by more than 17.6 degrees or 9.0 degrees postoperatively. PMID- 26559290 TI - Diagnostic Performance of Diffusion-weighted Magnetic Resonance Imaging in Bone Malignancy: Evidence From a Meta-Analysis. AB - Current state-of-the-art nuclear medicine imaging methods (such as PET/CT or bone scintigraphy) may have insufficient sensitivity for predicting bone tumor, and substantial exposure to ionizing radiation is associated with the risk of secondary cancer development. Diffusion-weighted MRI (DW-MRI) is radiation free and requires no intravenous contrast media, and hence is more suitable for population groups that are vulnerable to ionizing radiation and/or impaired renal functions. This meta-analysis was conducted to investigate whether whole-body DW MRI is a viable means in differentiating bone malignancy. Medline and Embase databases were searched from their inception to May 2015 without language restriction for studies evaluating DW-MRI for detection of bone lesions. Methodological quality was assessed by the quality assessment of diagnostic studies (QUADAS-2) instrument. Sensitivities, specificities, diagnostic odds ratio (DOR), and areas under the curve (AUC) were used as measures of the diagnostic accuracy. We combined the effects by using the random-effects mode. Potential threshold effects and publication bias were investigated. We included data from 32 studies with 1507 patients. The pooled sensitivity, specificity, and AUC were 0.95 (95% CI, 0.90-0.97), 0.92 (95% CI, 0.88-0.95), and 0.98 on a per patient basis, and they were 0.91 (95% CI, 0.87-0.94), 0.94 (95% CI, 0.90-0.96), and 0.97 on a per-lesion basis. In subgroup analysis, there is no statistical significance found in the sensitivity and specificity of using DWI only and DWI combined with other morphological or functional imaging sequence in both basis (P > 0.05). A b value of 750 to 1000 s/mm enables higher AUC and DOR for whole-body imaging purpose when compared with other values in both basis either (P < 0.01). The ROC space did not show a curvilinear trend of points and a threshold effect was not observed. According to the Deek's plots, there was no publication bias on both basis. Our results support the use of DWI as an effective means for distinguishing malignant bone lesions; however, various imaging parameters need to be standardized prior to its broad use in clinical practice. PMID- 26559291 TI - Kinetic Changes of Viremia and Viral Antigens of Hepatitis B Virus During and After Pregnancy. AB - Whether pregnancy may influence the replication of hepatitis B virus (HBV) remains unknown. The authors aimed to clarify this issue by observing the kinetics of HBV deoxyribonucleic acid (DNA) and viral antigens in women during and after pregnancy. Total, 371 pregnant women with positive hepatitis B surface antigen (HBsAg) were enrolled. Serial sera collected during and after pregnancy were quantitatively measured for HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg). Total, 34 HBeAg-positive women underwent alanine aminotransferase (ALT) elevation during or after pregnancy; levels of HBV DNA and HBsAg in them showed no obvious change between second trimester or delivery and 7 to 12 months postpartum (P > 0.05). The 337 others had normal alanine aminotransferase levels during pregnancy and postpartum. In 147 HBeAg-positive women with follow-up 7 to 12 months postpartum, the average levels of HBV DNA (>7.0 log10 IU/mL), HBsAg (>4.0 log10 IU/mL), and HBeAg (>3.0 log10 S/CO) were longitudinally constant during pregnancy and postpartum, respectively. In 173 women with follow-up 4.8 years postpartum, neither HBV DNA levels nor antigen titers showed significant difference between second trimester and 4.8 years postpartum, regardless of the HBeAg status. In addition, levels of HBV DNA and viral antigens in second trimester, around delivery, 6 to 8 weeks and 7 to 12 months postpartum showed no marked fluctuations, respectively. Serum levels of HBV DNA and viral antigens in HBsAg-positive women are highly constant during pregnancy and postpartum, regardless of the HBeAg status and alanine aminotransferase levels. This demonstrates that pregnancy has little influence on the HBV replication and antigen expression. PMID- 26559292 TI - Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases. AB - Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL 10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-alpha) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 * ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-alpha and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 * ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75 0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL 11 was independently associated with at least moderate inflammation, whereas IL 2R and TGF-alpha were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-alpha based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT. PMID- 26559293 TI - Decreased Expression of SETD2 Predicts Unfavorable Prognosis in Patients With Nonmetastatic Clear-Cell Renal Cell Carcinoma. AB - DNA sequencing revealed that mutations in SETD2 occur in 3% to 12% of clear-cell renal cell carcinoma (ccRCC) cases and are associated with poor clinical outcome. In this study, we used an immunohistochemistry (IHC) assay to evaluate the impact of SETD2 loss, with expression of H3K36me3, a nonredundantly histone modification by SETD2, on recurrence and survival of nonmetastatic ccRCC patients after nephrectomy.SETD2 and H3K36me3 were assessed in 192 nonmetastatic ccRCC patients enrolled retrospectively from a single institution. Kaplan-Meier and Cox regression analysis were used to associate prespecified SETD2/H3K36me3 score with overall survival (OS) and recurrence-free survival (RFS). And a nomogram was constructed to predict OS at 10 years.Patients with low expression of SETD2 were prone to possess large tumor size and advanced pT stage. And low H3K36me3 expression was associated with larger tumor size. A prespecified combined score based on SETD2 and H3K36me3 expression remained an independent prognosticator for OS and RFS, which was associated with tumor size, pT stage, and sarcomatoid. Furthermore, using prespecified SETD2/H3K36me3 score could stratify nonmetastatic ccRCC patients into different risk subgroups, especially in patients dichotomized by pT stage and Fuhrman grade, respectively. Finally, the C-index for predicting OS increased from 0.727 to 0.747, after adding SETD2/H3K36me3 score to pT stage and Fuhrman grade.The combined score based on expression of SETD2 and H3K36me3 using IHC could predict poor clinical outcomes in nonmetastatic ccRCC patients, and it may benefit preoperative risk stratification and guide treatment planning in the future. PMID- 26559294 TI - Continuous Local Infiltration Analgesia for Pain Control After Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials. AB - A total knee arthroplasty (TKA) has always been associated with moderate to severe pain. As more research is conducted on the use of continuous local infiltration analgesia (CLIA) to manage pain after a TKA, it is necessary to reassess the efficacy and safety of the TKA method. The purpose of this systematic review and meta-analysis of randomized controlled trials was to evaluate the efficacy and safety of pain control of CLIA versus placebo after a TKA. In January 2015, a systematic computer-based search was conducted in the Medline, Embase, PubMed, CENTRAL (Cochrane Controlled Trials Register), Web of Science, Google database, and Chinese Wanfang databases. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement criteria. The primary endpoint was the visual analog scale score after a TKA with rest or mobilization at 24, 48, and 72 hours, which represents the effect of pain control after TKA. The complications of infection, nausea, and whether it prolonged wound drainage were also compiled to assess the safety of CLIA. RevMan 5.30 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, data were aggregated for random-effects modeling when necessary. Ten studies involving 735 patients met the inclusion criteria. The meta-analysis revealed that continuous infusion analgesia provided better pain control with rest at 24 hours (mean difference [MD] -12.54, 95% confidence interval [CI] 16.63 to 8.45), and with mobilization at 24 hours (MD -18.27, 95% CI -27.52 to 9.02) and 48 hours (MD -14.19, 95% CI -21.46 to 6.93). There was no significant difference with respect to the visual analog scale score at 48 hours (MD -6.15, 95% CI -13.51 to 1.22, P = 0.10) and 72 hours (MD -3.63, 95% CI -10.43 to 3.16, P = 0.29) with rest and at 72 hours with mobilization (MD -4.25, 95% CI -16.27 to 7.77, P = 0.49). However, CLIA increased the rate of infection (relative risk [RR] 3.16, 95% CI 1.18-8.50, P = 0.02) and the rate of nausea or vomiting (RR 0.60, 95% CI 0.37-0.96, P = 0.03). There were no significant differences in the length of hospital stay (MD -0.34, 95% CI -1.09 to 0.42, P = 0.38), deep venous thrombosis (RR 1.02, 95% CI 0.30 to 1.41, P = 0.99), or duration of surgery (MD 1.20, 95% CI -4.59 to 6.98, P = 0.69). On the basis of the current meta-analysis, CLIA was more efficacious for reducing postoperative pain than the placebo at 24 hours with rest and at 24 and 48 hours with mobilization, but it increased the risk of infection. However, CLIA did not prolong the length of hospital stay or the duration of surgery. There was also a higher heterogeneity of different analgesic drugs mixed and a high risk of selection bias in this analysis; therefore, more high-quality randomized controlled trials with standardized CLIA are necessary for proper comparisons of this technique with other methods. PMID- 26559295 TI - Neuron-Specific Enolase, S100 Calcium-Binding Protein B, and Heat Shock Protein 70 Levels in Patients With Intracranial Hemorrhage. AB - The authors evaluated neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and heat shock protein 70 (HSP 70) levels and their relationships with in-hospital mortality, Glasgow Coma Scale (GCS) scores, and National Institute of Health Stroke Scale (NIHSS) scores. In total, 35 patients older than 18 years were presented to our emergency department and were diagnosed with non-traumatic intracranial hemorrhage (ICH) and 32 healthy controls were included. Blood samples were drawn on days 0 and 5. S100 calcium-binding protein B and HSP levels were significantly higher in patients than in controls on days 0 and 5. Neuron specific enolase levels were higher in patients than in controls on day 0, but there was no significant difference on day 5. S100 calcium-binding protein B was negatively correlated with GCS, whereas it was positively correlated with NIHSS and bleeding volume. There was also a negative correlation between NSE and GCS, but it was not statistically significant. In addition, no significant correlation was found in terms of bleeding volume or NIHSS. Heat shock protein 70 was negatively correlated with GCS and positively correlated with bleeding volume and NIHSS, but these results were not statistically significant. S100 calcium-binding protein B and HSP 70 levels were significantly higher in those who died compared with survivors. The areas under the curve of S100 B, NSE, and HSP 70 for mortality were 0.635, 0.477, and 0.770, respectively. Neuron-specific enolase, S100B, and HSP 70 levels are simple, inexpensive, and objective measures in cases of ICH. These tests can be used to support an assessment for screening ICH patients with clinical scoring systems, such as GCS and NIHSS. PMID- 26559296 TI - Postoperative Pain and Intravenous Patient-Controlled Analgesia-Related Adverse Effects in Young and Elderly Patients: A Retrospective Analysis of 10,575 Patients. AB - In this retrospective analysis of 10,575 patients who used fentanyl-based intravenous patient-controlled analgesia (IV-PCA) after surgery, we evaluated difference between young and elderly patients on their characteristic of adverse effects.We reviewed the data collected from the patients who were provided IV-PCA for pain control following elective surgery under either general or spinal anesthesia between September 2010 and March 2014. Postoperative pain, incidence of PCA-related adverse effects, and risk factors for the need of rescue analgesics and antiemetics for postoperative 48 hours were analyzed.Pain intensity (numerical rating scale [NRS]) at postoperative 6 to 12 hours (4.68 vs 4.58, P < 0.01) and incidence of nausea or vomiting (23.8% vs 20.6%, P < 0.001) were higher in young patients, while incidence of PCA discontinuation (9.9% vs 11.5%, P < 0.01) and sedation (0.1% vs 0.7%, P < 0.001) was higher in elderly patients. Despite larger fentanyl dose used, a greater proportion of young patients required rescue analgesics (53.8% vs 47.9%, P < 0.001) while addition of ketorolac was effective in reducing postoperative pain. Despite lower incidence of postoperative nausea and vomiting (PONV), a larger proportion of elderly patients required rescue antiemetics (10.1% vs 12.2%, P < 0.001) while addition of ramosetron was effective in reducing PONV.In conclusion, when fentanyl-based IV-PCA is used for postoperative pain control, a larger proportion of young patients may require rescue analgesics while elderly patients may require more rescue antiemetics. The addition of ketorolac or ramosetron to the PCA of young and elderly patients can be effective to prevent rescue analgesics or antiemetics use. PMID- 26559297 TI - Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy. AB - The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic Tc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative Tc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters.Quantitative Tc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters. PMID- 26559298 TI - Survival Prediction Model Using Clinico-Pathologic Characteristics for Nonsmall Cell Lung Cancer Patients After Curative Resection. AB - The current TNM staging system did not provide disease relapse information. The aim of study was try to establish a predictive survival model for disease and overall survival in nonsmall cell lung cancer patients who presented as resectable disease and to develop a reference for follow-up imaging tool selection.From January 2005 to December 2011, 442 patients who initially presented as resectable disease (stages I-IIIa) and received anatomic resection and mediastinal lymph node dissection were included in the study.Medical charts were thoroughly reviewed and clinico-pathologic factors were collected and analyzed.Visceral pleural invasion, tumor size >5 cm, and postoperative adjuvant therapy were identified as risk factors for poorer disease-free survival. The 5 year disease-free survival from score 0 to 3 was 68.7%, 46.6%, 31.9%, and 26.1%, respectively. The disease relapse percentage for scores 0 to 3 were 26.49%, 50.61%, 65.05%, and 73.81%, respectively. For analysis of overall survival, age >60 years, tumor size >3 cm, and total metastatic lymph node ratio >0.05 were correlated to worse overall survival. Because greater age may be correlated with poor general condition, we re-scored risk factors that correlated to disease severity that ranging from 0 to 2. The 5-year overall survival range from score 0 to 2 was 56.3%, 43.1%, and 13.1%, respectively.Poor prognostic factors correlated to disease-free survival were tumor size >5 cm, visceral pleural invasion, and patients needing to receive postoperative adjuvant therapy. Disease-free survival of resectable nonsmall cell lung cancer patients and disease relapse can be stratified by these 3 factors. Chest tomography may be recommended for patients with 1 or more poor disease-free survival risk factors. PMID- 26559299 TI - Prognostic Value of Serum Tumor Markers in Medullary Thyroid Cancer Patients Undergoing Vandetanib Treatment. AB - Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet.Twenty-one patients (male, 16, female, 5; mean age, 49 +/- 13 years) with progressive MTC receiving vandetanib (300 mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD).During long-term follow-up (510 +/- 350 days [range, 97-1140 days]), CTN and CEA levels initially dropped in 71.4% and 61.9% of the patients followed by fluctuations in serum marker levels. A rise in CTN >=39.5% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6% and a specificity of 83.2% in predicting PD with an accuracy of 82.0% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD.Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN >=40% turns out to as an early indicator of tumor progression. PMID- 26559300 TI - Prevalence and Predictive Factors of Chronic Postsurgical Pain and Global Surgical Recovery 1 Year After Outpatient Knee Arthroscopy: A Prospective Cohort Study. AB - Outpatient knee arthroscopy is one of the most commonly performed surgical procedures. Previous research has demonstrated that chronic postsurgical pain (CPSP) after outpatient surgery is prevalent. Our objective was to determine the prevalence and predictive factors of CPSP and Global Surgical Recovery (GSR) 1 year after knee arthroscopy.A prospective longitudinal cohort study was performed. Patients were included during an 18-month period. Data were collected by using 3 questionnaires: at 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale (NRS) was defined as moderate to severe pain. A score of <=80% on the Global Surgical Recovery Index was defined as poor GSR. Stepwise logistic regression analysis was performed to determine which variables were predictors for CPSP and poor GSR.The prevalence of moderate to severe preoperative pain in patients undergoing knee arthroscopy (n = 104) was 71.2%, of acute postsurgical pain 37.5%, and of CPSP 32.7%. Risk factors for CPSP were the presence of preoperative pain and preoperative analgesic use, with odds ratios of 6.31 (1.25-31.74) and 4.36 (1.58 12.07), respectively. The prevalence of poor GSR 1 year after outpatient knee arthrosocpy was 50.0%. Poor GSR 4 days after the surgery was a risk factor with an odds ratio of 8.38 (0.92-76.58) and quality of life 4 days after surgery was a protective factor with and odds ratio of 0.10 (0.02-0.64).Both CPSP and poor GSR are common 1 year after knee arthroscopy. Patients at risk for CPSP can be identified during the preoperative phase. Prediction of poor GSR 1 year after surgery is mainly related to early postoperative recovery. PMID- 26559301 TI - Association Between Statin Use and Open-angle Glaucoma in Hyperlipidemia Patients: A Taiwanese Population-based Case-control Study. AB - The aim of the study was to investigate the association between statin use and open-angle glaucoma (OAG) risk in hyperlipidemia patients.We used the research database of the Taiwan National Health Insurance program to conduct a population based case-control study. A total of 1276 patients with newly diagnosed OAG were identified from 2004 to 2011. Controls comprised of 12,760 patients without glaucoma and were frequency-matched for age, sex, history of diabetes mellitus, and year of hyperlipidemia diagnosis at a 1:10 ratio. Accumulated defined daily doses (DDDs) of statins prescribed during follow-up were calculated. Average statin use was calculated as the sum of DDDs divided by the duration from the initial statin prescription date to the index date (per year), and was subdivided into 3 levels: <30, 30 to 119, and >=120 DDDs. Comorbidity, including hypertension, depression, and the Charlson comorbidity index, the frequency of eye care visits, and the use of nonstatin cholesterol-lowering drugs, were all considered as confounding factors.For the group with statin use, the adjusted odds ratio of OAG was 1.02 (95% confidence interval 0.90-1.15) when compared with the group without statin use. Subanalysis showed that a high dosage of statin use (>=120 DDD/y) resulted in a1.24-fold increased risk of OAG (odds ratio 1.24, 95% confidence interval 1.03-1.49). The incidence of OAG was increased with the increase of the dosage of statin use (P for trend = 0.0458).Clinicians should be cautious of hyperlipidemia patients with a high dosage of statin use because it might be associated with an increased risk of OAG. Ophthalmologist consultation is necessary for this high-risk group. PMID- 26559303 TI - Case Report of Multimodality Imaging in Omental Cake: Plain Radiograph, Computed Tomography, and Ultrasonography: A Care-Compliant Article. AB - The imaging finding of omental cake has been demonstrated in other modalities, such as computed tomography, magnetic resonance imaging, and ultrasonography. However, to the best of our knowledge, the image presentation of omental cake on a routine kidney-ureter-bladder film has not been reported before in the literature. We presented a unique case of a 61-year-old woman, with known advanced cecal colon mucinous adenocarcinoma, presented to our institution with abdominal fullness, poor appetite, and decreased stool passage for 20 days. Physical examination was unremarkable, except distended abdomen. Subsequent study revealed massive post-pigtail catheter drainage ascites with a prominent soft tissue mass-causing centralization and tethering of focally distended small bowel gas, suggestive of omental cake on plain radiograph. The imaging finding in plain radiograph corresponds to the findings in other imaging modalities, including abdominal sonography and computed tomography. The patient underwent subtotal colectomy and ileostomy during later courses of chemotherapy due to adhesion ileus and possible intraabdominal abscess, and pathologic study confirmed the diagnosis of cecal mucinous adenocarcinoma and peritoneal carcinomatosis. Although the image finding of omental cake on plain radiograph has never been described, this image finding is unique and should be recognized, as it may suggest the presence of omental cake when first identified in the emergency department from patients with abdominal distension and warrant further evaluation to evaluate the underlying cause. PMID- 26559302 TI - Increased Risk of Acute Coronary Syndrome in Patients With Diverticular Disease: A Nationwide Population-Based Study. AB - Diverticular disease and acute coronary syndrome (ACS) are common disorders that share several risk factors. Few researchers have evaluated the association between diverticular disease and ACS. We aimed to assess the risk of ACS in patients with diverticular disease. A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. All patients aged >=20 years with a diagnosis of diverticular disease from January 1, 2000, to December 31, 2011, were included in this study. For comparison, patients without diverticular disease were randomly selected and matched with the study cohort at a 4:1 ratio according to age, sex, and the year of the diagnosis of diverticular disease. Patients with incomplete age or sex information and a history of cardiovascular diseases were excluded from the study. All patients were followed until an ACS event, withdrawal from the insurance program, or December 31, 2011. In this study, 52,681 patients with diverticular disease and 210,724 patients without diverticular disease were included. Men accounted for 56.1% of patients and 57.8% of patients were >=50 years old. The overall incidence density of ACS in patients with diverticular disease (45.5 per 10,000 person-years) was significantly higher than in those without diverticular disease (30.3 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.23 (95% confidence interval [CI], 1.14-1.32) after adjustment for age, sex, and comorbidities. The cumulative incidence of ACS in patients with diverticular disease was significantly higher than that in the control cohort (log-rank test, P < 0.001). The adjusted HRs for the development of ACS were 1.25 (95% CI, 1.15-1.37) and 1.19 (95% CI, 1.07-1.32) in patients with diverticulitis and diverticulosis, respectively. The adjusted HRs of ACS in patients with diverticular disease additionally increased from 1.97 (95% CI, 1.73 2.23) in patients with 1 comorbidity to 5.51 (95% CI, 3.88-7.84) in those with >=5 comorbidities. This large population-based retrospective study revealed an association between diverticular disease and ACS. Further research is warranted to determine the exact mechanism of the link between these diseases. PMID- 26559304 TI - Serum TRSUT Titer >=1: 16 Is a Predictor for Neurosyphilis Among HIV-Infected Patients With Concurrent Syphilis and No Neurological Symptoms. AB - Investigating the predictors for lumbar puncture to diagnose the asymptomatic neurosyphilis among HIV and syphilis co-infected patients in Shanghai, China. Respectively, screening the medical records from August 1, 2009 to June 30, 2015. Those HIV-infected patients with concurrent syphilis who had received lumbar puncture were selected and their clinical and demographic data were recorded. Participants comprised symptomatic and asymptomatic patients. The latter ones could be further divided into 3 groups: late syphilis, early syphilis with anti syphilis treatment failure, and early syphilis with serum toludine red unheated serum test (TRUST) >=1:32. Both syphilis stage and anti-syphilis treatment effect were defined by common criteria, and syphilis of unknown duration was considered as late syphilis. Asymptomatic neurosyphilis was defined as neurosyphilis without neurological symptoms such as headache, cognitive dysfunction, motor deficits, auditory or ophthalmic abnormalities, and stroke. Neurosyphilis was defined as reactive cerebrospinal fluid (CSF) TRUST and/or CSF white blood cell >20 cells/MUL without other reasons. Mann-Whitney test and Fisher's exact test were used for analyzing the difference between neurosyphilis and non-neurosyphilis group. Logistic regression test was performed to analyze the risk factors for neurosyphilis. In total, 170 participants were collected, and the rate of neurosyphilis was 32.35%. Among all the 105 participants without neurological symptoms, 80 patients were with late syphilis and 25 were with early syphilis. Among the early syphilis patients, 23 had a TRUST >=1:32 and the other 2 experienced an anti-syphilis treatment failure. The differences of clinical and demographic variables between neurosyphilis and non-neurosyphilis group were not statistically significant except the serum TRUST titer (P < 0.01). From HIV/syphilis co-infected patients with or without neurological symptom, those who had neurological symptoms, CD4 <350 per MUL and serological TRUST titer >=1:16 were 4.9-fold (95% confidence interval [CI]: 2.37-10.31), 4.3-fold (95% CI: 1.17 15.78), and 4.1-fold (95% CI: 1.58-10.76), respectively, more likely to be diagnosed with neurosyphilis. Asymptomatic patients whose serum TRUST titer >=1:16 were 8.48-fold (95% CI: 1.08-66.63) more likely to have asymptomatic neurosyphilis. Among asymptomatic HIV-infected patients with late syphilis or early syphilis experienced an anti-syphilis treatment failure, those who have a serum TRUST titer >=1:16 are suggested to perform lumbar puncture in order to avoid delayed diagnosis and the occurrence of severe sequelae of syphilis. PMID- 26559305 TI - Risk Factors for Long-Term Mortality and Progressive Chronic Kidney Disease Associated With Acute Kidney Injury After Cardiac Surgery. AB - The aim of the study was to evaluate risk factors for long-term mortality and progressive chronic kidney disease (CKD) after cardiac surgery in patients with normal preoperative renal function and postoperative acute kidney injury (AKI). From April 2009 to December 2012, we prospectively enrolled 3245 cardiac surgery patients of our hospital. The primary endpoints included survival rates and the secondary endpoint was the incidence of progressive chronic kidney disease (CKD) in a follow-up period of 2 years. Acute kidney injury was staged by KDIGO classification. Progressive CKD was defined as GFR <= 30 mL/min/1.73 m or end stage renal disease (ESRD) (starting renal replacement therapy or renal transplantation).The AKI incidence was 39.9% (n = 1295). The 1 and 2 year overall survival (OS) rates of AKI patients were significantly lower than that for non AKI patients (85.9% and 82.3% vs 98.1% and 93.7%, P < 0.001), even after complete recovery of renal function during 2 years after intervention (P < 0.001). The 2 year overall survival (OS) rates of patients with AKI stage 1, 2, and 3 were 89.9%, 78.6%, and 61.4% (P < 0.001), respectively. Multivariate Cox regression analysis of factors for 2-year survival rates revealed that besides age (P < 0.001), chronic cardiac failure (P < 0.001), diabetes (P < 0.001), cardiopulmonary bypass time (P < 0.01), and length of intensive care unit (ICU) stay (P = 0.004), AKI was a significant risk factor for reducing 2-year survival rates even after complete recovery of renal function (P < 0.001). The accumulated progressive CKD prevalence was significantly higher in AKI than in non-AKI patients (6.8% vs 0.2%, P < 0.001) in the 2 years after surgery. Even with complete recovery of renal function at discharge, AKI was still a risk factor for accumulated progressive CKD (RR 1.92, 95% CI 1.37-2.69).The 2-year mortality and progressive CKD incidence even after complete recovery of renal function were significantly increased in cardiac surgery patients with postoperative AKI. PMID- 26559306 TI - Medical Malpractice in Wuhan, China: A 10-Year Autopsy-Based Single-Center Study. AB - Medical disputes in China are historically poorly documented. In particular, autopsy-based evaluation and its impact on medical malpractice claims remain largely unstudied. This study aims to document autopsy findings and medical malpractice in one of the largest cities of China, Wuhan, located in Hubei Province. A total of 519 autopsies were performed by the Department of Forensic Medicine, Wuhan University School of Medicine, Wuhan, China, over a 10-year period between 2004 and 2013. Of these cases, 190 (36.6%) were associated with medical malpractice claims. Joint evaluation by forensic pathologists and clinicians confirmed that 97 (51.1%) of the 190 claims were approved medical malpractice cases. The percentage of approved malpractice cases increased with patient age and varied according to medical setting, physician specialty, and organ system. The clinico-pathological diagnostic discrepancy was significantly different among various physician specialties (P = 0.031) and organ systems (P = 0.000). Of those cases involved in malpractice claims, aortic dissection, coronary heart disease, and acute respiratory infection were most common. Association between incorrect diagnosis and malpractice was significant (P = 0.001). This is the first report on China's medical malpractice and findings at autopsy which reflects the current state of health care services in one of the biggest cities in China. PMID- 26559307 TI - Comparison of Clinical and Radiological Improvement Between the Modified Trephine and High-speed Drill as Main Osteotomy Instrument in Pedicle Subtraction Osteotomy. AB - High-speed drill is the main osteotomy instrument in pedicle subtraction osteotomy (PSO) currently. Considering the long duration of surgery, the large amount of blood loss, and the high incidence of neurovascular injury, the osteotomy procedure is challenging. Use of trephine for the osteotomy displays high efficiency by shortening surgery time and reducing blood loss in anterior cervical corpectomy and fusion. However, the potential risk of neurological injury is high. We modified the trephine by adding locking instrument, when the serrated top of the trephine reaches the tip of the probe; the locking instrument on the probe restricts the trephine and improves security during the osteotomy procedure.The aim of this study was to compare the clinical and radiological improvement between the modified trephine and high-speed drill as main osteotomy instrument in PSO.From February 2009 to 2013, 50 patients with severe thoracolumbar kyphotic deformity caused by old compressive vertebrae were prospectively reviewed. All patients were randomly assigned to the experimental group (27 patients received PSO with modified trephine) and the control group (23 patients received PSO with high-speed drill). The clinical records were reviewed and compared for surgical time, operative blood loss, functional improvement (Oswestry Disability Index), and pain relief (visual analog scale). The radiological records were reviewed and compared for correction of kyphotic deformity postoperatively and correction loss at 2-year follow-up.All patients successfully finished the PSO procedure, and got satisfactory kyphotic deformity correction and overall function improvement. The surgery time was shorter in the experimental group than that in the control group (132.7 +/- 12.6 vs 141.7 +/- 16.7 min; P = 0.03). No significant difference was found in blood loss (882.9 +/- 98.9 mL vs 902.2 +/- 84.9 mL; P = 0.47) or correction of the kyphotic angle (33.4 +/- 3.4 degrees vs 32.1 +/- 2.5 degrees , P = 0.13) postoperatively between the 2 groups. At 24-month follow-up, no difference was discovered in loss of the correction (4.9 +/- 1.6 degrees vs 4.5 +/- 1.6 degrees ; P = 0.42), change of Oswestry Disability Index (49.4 +/- 6.2% vs 48.2 +/- 4.2%; P = 0.44), or in back pain relief (6.2 +/- 1.4 vs 6.4 +/- 1.2 min; P = 0.51) between the 2 groups. No internal fixation related complication occurred and bony fusion was detected in lateral X-ray in all patients. In the control group, 2 patients had transient nerve root deficit, 14 patients at 3-month follow-up and 3 patients at 2-year follow-up experienced graft donor site morbidity, and pain killer medicine was always required.In conclusion, the modified trephine obviously shortens surgery time, and prevents graft donor site morbidity when compared to a high-speed drill. The learning curve for using the modified trephine in PSO procedure is short. PMID- 26559308 TI - An Exploration of the Role of MicroRNAs in Psoriasis: A Systematic Review of the Literature. AB - Psoriasis is recently characterized by a specific microRNAs (miRNAs) expression profile, which guides the researchers' efforts to explore the therapeutic targets and objective biomarkers that reflect the diagnosis and disease activity in clinical use for psoriasis.The paper presents a state-of-the-art review of expression and function of miRNAs in psoriasis along with its clinical implications.We analyzed all literature searched by keywords "microRNA" and "psoriasis" in PubMed (Medline) from inception up to July 2015, and the references in the literature searched were also considered.Relevant literature was chosen according to the objective of this review. Relevant literature was searched by 3 independent investigators, and experts in the field of miRNAs and psoriasis were involved in analyzing process.We included any study in which role of miRNAs in psoriasis was examined in relation to disease pathogenesis, diagnosis, and treatment.The specific miRNAs profile has been identified from human psoriatic skin, blood, and hair samples. It is found that genetic polymorphisms related to some of specific miRNAs, miR-146a for example, are associated with psoriasis susceptibility. Key roles of several unique miRNAs, such as miR-203 and miR-125b, in inflammatory responses and immune dysfunction, as well as hyperproliferative disorders of psoriatic lesions have been revealed. Moreover, circulating miRNAs detected from blood samples have a potential of clinic application to be the biomarkers of diagnosis, prognosis, and treatment responses. Additionally, a new layer of regulatory mechanisms mediated by miRNAs is to some extent revealed in pathogenesis of psoriasis.The dramatically altered mRNA expression profiles are displayed in psoriasis, and some of these may become disease markers and therapeutic targets. Herein, this work underscores the potential importance of miRNAs to diagnosis, prognosis, and treatment of psoriasis. However, further study in this field is worth doing in the future, as the exact roles of miRNAs in psoriasis have not been fully elucidated.Systematic review registration number is not registered. PMID- 26559309 TI - Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression. AB - The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI.They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions.Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain.Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD. PMID- 26559310 TI - Perioperative Blood Glucose Levels <150 mg/dL are Associated With Improved 5-Year Survival in Patients Undergoing On-Pump Cardiac Surgery: A Prospective, Observational Cohort Study. AB - Hyperglycemia is common during and after Coronary Artery Bypass Graft Surgery (CABGS) and has been shown to be associated with poor clinical outcomes. In this study, we hypothesized that a moderate perioperative mean blood glucose level of <150 mg/dL improves long-term survival in cardiac surgery patients. We conducted a prospective, observational cohort study in the heart center of the University Medical Center of Goettingen, Germany. Patients undergoing on-pump cardiac surgery were enrolled in this investigation. After evaluating perioperative blood glucose levels, patients were classified into 2 groups based on mean glucose levels: Glucose >=150 mg/dL and Glucose <150 mg/dL. Patients were followed up for 5 years, and mortality within this period was recorded as the primary outcome parameter. Secondary outcome parameters included the length of ICU stay, the use of inotropic agents, the length of hospital stay, and the in-hospital mortality. A total of 455 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass were enrolled in this investigation. A Kaplan-Meier survival analysis of the 5-year mortality risk revealed a higher mortality risk among patients with glucose levels >=150 mg/dL (P = 0.0043, log-rank test). After adjustment for confounders in a multivariate Cox regression model, the association between glucose >=150 mg/dL and 5-year mortality remained significant (hazard ratio, 2.10; 95% CI, 1.30-3.39; P = 0.0023). This association was corroborated by propensity score matching, in which Kaplan-Meier survival analysis demonstrated significant improvement in the 5-year survival of patients with glucose levels <150 mg/dL (P = 0.0339). Similarly, in-hospital mortality was significantly higher in patients with glucose >=150 mg/dL compared with patients with glucose <150 mg/dL. Moreover, patients in the Glucose >=150 mg/dL group required significantly higher doses of the inotropic agent Dobutamine (mg/d) compared with patients in the Glucose <150 mg/dL group (20.6 +/- 62.3 and 10.5 +/ 40.7, respectively; P = 0.0104). Moreover, patients in the Glucose >=150 mg/dL group showed a significantly longer hospital stay compared with patients in the Glucose <150 mg/dL group (28 +/- 23 and 24 +/- 19, respectively; P = 0.0297). We conclude that perioperative blood glucose levels <150 mg/dL are associated with improved 5-year survival in patients undergoing cardiac surgery. More studies are warranted to explain this effect. PMID- 26559311 TI - Long-Term Use of Selective Serotonin Reuptake Inhibitors and Risk of Glaucoma in Depression Patients. AB - This study investigated whether the long-term use of selective serotonin reuptake inhibitors (SSRIs) influences the risk of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) in the Chinese ethnic population in Taiwan.The authors retrieved the data under analysis from the National Health Insurance Research Database in Taiwan and identified 26,186 newly diagnosed depression patients without preexisting glaucoma. The study cohort included 13,093 patients with over 1 year of SSRI use, and a comparison cohort of 13,093 patients who had never used SSRIs. The main outcome was a diagnosis of POAG or PACG during follow-up. The authors used univariable and multivariable Cox proportional hazards regression models to assess the effects of SSRIs on the risk of POAG and PACG.The cumulative incidences of POAG and PACG between the SSRI and comparison cohorts exhibited nonsignificant differences (log-rank test P = .52 for POAG, P = .32 for PACG). The overall incidence of POAG in the SSRI cohort was nonsignificantly higher than that in the comparison cohort (1.51 versus 1.39 per 1000 person-years), with an adjusted hazard ratio of 1.07 (95% confidence interval = 0.82-1.40). The overall incidence of PACG in the SSRI cohort was nonsignificantly lower than that in the comparison cohort (0.95 versus 1.11 per 1000 person-years), with an adjusted hazard ratio of 0.85 (95% confidence interval = 0.62-1.18).The long-term use of SSRIs does not influence the risk of POAG or PACG in depression patients. PMID- 26559312 TI - Extensive Metastatic Cholangiocarcinoma Associated With IgG4-Related Sclerosing Cholangitis Misdiagnosed as Isolated IgG4-Related Sclerosing Cholangitis: A Case Report and Literature Review. AB - As cholangiographic features of IgG4-related sclerosing cholangitis (IgG4-SC) resemble those of cholangiocarcinoma, it is highly confusing between the 2 conditions on the basis of cholangiographic findings. This study presents a case of extensive metastatic cholangiocarcinoma with IgG4-SC misdiagnosed as isolated IgG4-SC, and reviews recent studies of the 2 diseases.A 56-year-old man with no family history of malignant tumors or liver diseases presented with recurrent mild abdominal pain and distention for 3 months. Magnetic resonance cholangiopancreatography showed a 3.7 cm nodular lesion with unclear boundary in segment VI of the liver. Serum IgG4 and CA19-9 were slightly elevated. Histopathological examination was consistent with the consensus statement on the pathology of IgG4-SC. IgG4-SC was thus considered. Due to his mild symptoms, glucocorticoid was not given at first. However, 3 months after his first admission, he had more severe abdominal pain and further elevated serum CA19-9. Actually he was found suffering from extensive metastatic cholangiocarcinoma with IgG4-SC by exploratory laparotomy.The present case serves as a reminder that extensive metastatic cholangiocarcinoma with or without IgG4-SC may be misdiagnosed as an isolated IgG4-SC case if one relies solely on elevated serum and tissue IgG4 levels. We emphasize on the importance of repeated core needle biopsy or exploratory laparoscopy/laparotomy before immunosuppressive drugs are given, and on follow-up of imaging findings and serum CA19-9 once immunosuppressive therapy is started. PMID- 26559313 TI - Initial and Middle-Term Outcome of Treatment for Spontaneous Isolated Dissection of Superior Mesenteric Artery. AB - Symptomatic isolated dissection of the superior mesenteric artery (SIDSMA) represents an extremely rare condition. Although various treatments including conservative treatment, endovascular stenting (ES), and surgical repair are currently available, consensus treatment guideline is absent due to scarce of SIDSMA cases. Thus, we present our experience in the treatment of SIDSMA at our single center.Fourteen cases of SIDSMA were treated with conservative treatment, catheter-directed thrombolysis (CDT), endovascular stenting (ES), or surgical repair at our center between January 2008 and January 2014. Demographics, clinical manifestations, coexisting medical conditions, imaging feature, treatments, and follow-up outcome of these patients were retrospectively collected and analyzed.For 13 patients without peritonitis, conservative treatment was given for 4 to 6 days initially. After the first observation cycle, symptoms and signs were alleviated in 8 patients, and conservative treatments were continued. The remaining 5 patients received technically and clinically successful ES (in 4) or CDT (in 1) due to worsening symptoms and signs during conservative treatment. One patient with peritonitis underwent emergency surgery, with the necrotic small intestine resected. However, the abdominal pain was not alleviated 17 days postoperatively, ES was thus performed and symptoms relieved immediately. Two weeks after ES, a new aneurysm and partial thrombosis in the distal part of the stent were found by computed tomography angiography in this patient. No intestinal infarction or mortality developed during hospitalization. Follow-up was accomplished in 11 cases, ranging from 4 to 74 months (23.5 +/- 21.3). Except that one complained with mild abdominal pain, the other 10 achieved complete remission. All patients were free from new aneurysmal formation of SMA and all stents remained patent.For SIDSMA without peritonitis, conservative treatment can be provided with reasonable success rate, while ES may serve as an effective alternative once conservative treatment fails. For SIDSMA with peritonitis, open surgery remains the treatment of choice by resection of necrotic intestine and revasculization. PMID- 26559314 TI - Factors Associated With Oncologic Outcomes Following Abdominoperineal or Intersphincteric Resection in Patients Treated With Preoperative Chemoradiotherapy: A Propensity Score Analysis. AB - Due to selection bias, the oncologic outcomes of APR and ISR have not been compared in an interpretable manner, especially in patients treated with preoperative CRT. To assess factors influencing oncologic outcomes in patients with locally advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) followed by abdominoperineal resection (APR) or intersphincteric resection (ISR).Between 2006 and 2011, 202 consecutive patients who underwent APR or ISR after preoperative CRT for locally advanced rectal cancer were enrolled in this study. The median follow-up period was 45.3 months (range: 5-85.2 months). Multivariate and propensity score matching (PSM) analyses were performed to reduce selection bias.Of the 202 patients, 40 patients (19.8%) underwent APR and 162 (80.2%) required ISR. In unadjusted analysis, patients undergoing APR had a higher 5-year local recurrence (P < 0.001) and distant metastasis rate (P = 0.01), respectively. However, the higher local recurrence rate for APR persisted even after PSM, and these findings were verified in the multivariate analyses. Moreover, patients with advanced tumors, as assessed by restaging magnetic resonance imaging and luminal circumferential involvement, had a significantly higher local recurrence rate after APR compared with ISR.This is the first PSM based analysis providing evidence of a worse oncologic outcome after APR compared with ISR. In addition, the results of the subgroup analysis suggest that a more radical modification of the current APR is required in cases of advanced cancer. PMID- 26559315 TI - Higher Frequency of CD4+CXCR5+ICOS+PD1+ T Follicular Helper Cells in Patients With Infectious Mononucleosis. AB - Follicular helper T (Tfh) cells are recognized as a distinct CD4helper T cell subset, and mainly dysregulated in the autoimmune disease, whether it plays a role in the infectious mononucleosis (IM) diseases is unknown. In this study, we found that the CD4CXCR5 Tfh cells were not significantly changed, but the CD4CXCR5ICOS and CD4CXCR5ICOSPD1 Tfh subsets were significantly increased in the IM patients, and all these cells were significantly changed after antiviral therapy. Second, only the numbers of CD4CXCR5ICOSPD1 Tfh cells correlated with the Epstein-Barr virus (EBV) DNA load, negatively correlated with the numbers of naive B cells and amount of IL-21, and positively correlated with the numbers of plasma cells, memory B cells, and atypical lymphocytes. Third, the frequency of CD4CXCR5ICOSPD1 Tfh subset was significantly higher in lymphadenectasis or hepatosplenomegaly patients, and associated with the level of alanine aminotransferase (ALT). All together, our findings discovered this CD4CXCR5ICOSPD1 Tfh cell subset might play an important role in the pathogenesis of IM. PMID- 26559316 TI - Vaccine candidates for malaria: what's new? AB - Although it is more than a decade since the parasite genome information was obtained, standardized novel genome-wide selection/prioritization strategies for candidacy of malaria vaccine antigens are still sought. In the quest to systematically identify candidates, it is impossible to overemphasize the usefulness of wheat germ cell-free technology in expressing quality proteins for the post-genome vaccine candidate discovery. PMID- 26559317 TI - Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. AB - BACKGROUND: Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors. METHODS: Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti-factor Xa activity, which is a measure of factor Xa inhibition by the anticoagulant. RESULTS: Among the apixaban-treated participants, anti-factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P<0.001), and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P<0.001); thrombin generation was fully restored in 100% versus 11% of the participants (P<0.001) within 2 to 5 minutes. Among the rivaroxaban-treated participants, anti factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P<0.001), and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P<0.001); thrombin generation was fully restored in 96% versus 7% of the participants (P<0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of participants, transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or thrombotic events were reported. CONCLUSIONS: Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects. (Funded by Portola Pharmaceuticals and others; ANNEXA-A and ANNEXA-R ClinicalTrials.gov numbers, NCT02207725 and NCT02220725.). PMID- 26559318 TI - Posterior-anterior(PA) pressure Puffin for measuring and treating spinal stiffness: Mechanism and repeatability. AB - BACKGROUND: Posterior-anterior (PA) pressure technique is widely used for assessing and treating spinal segments. PA pressure is manually applied and stiffness is subjectively assessed. The method has been deemed unreliable and is associated with occupational strain. OBJECTIVES: To introduce a new ergonomically designed hand-held device measuring spinal stiffness, and to assess its repeatability. DESIGN: Quasi experimental study. METHOD: A convenience sample of 30 university students, 20-30 years old was used. The participants were tested two consecutive days by two physical therapy students using the new device; the PA pressure Puffin. The spinal segments under study were L1, Th12, Th7 and Th6 which all were tested three times with 9 kg force by both testers, both days. Intra-class correlation coefficients (ICC3,k) were used to assess intra- and inter-tester repeatability and analysis of variance with alpha-level at 0.05 was used to assess differences in joint mobility at the four segments measured. Linear regression analyses were used to assess repeatability. RESULTS: Inter tester and intra-tester coefficients (ICCs) ranged from 0.88 to 0.97 and from 0.83 to 0.97, respectively. There was no significant difference in displacement between Th6 and Th7 but all other joints were significantly different from each other. Displacement was always significantly greater the second day compared with day one (p < 0.05). CONCLUSIONS: This close to final prototype of the PA pressure Puffin measures segmental spinal stiffness and its ergonomically designed handle provides a promising tool for physical therapists applying PA pressure. Further research is needed for validation and reliability assessments. PMID- 26559319 TI - Immediate effects of hip mobilization with movement in patients with hip osteoarthritis: A randomised controlled trial. AB - BACKGROUND: Mobilization with movement (MWM) has been shown to reduce pain, increase range of motion (ROM) and physical function in a range of different musculoskeletal disorders. Despite this evidence, there is a lack of studies evaluating the effects of MWM for hip osteoarthritis (OA). OBJECTIVES: To determine the immediate effects of MWM on pain, ROM and functional performance in patients with hip OA. DESIGN: Randomized controlled trial with immediate follow up. METHOD: Forty consenting patients (mean age 78 +/- 6 years; 54% female) satisfied the eligibility criteria. All participants completed the study. Two forms of MWM techniques (n = 20) or a simulated MWM (sham) (n = 20) were applied. PRIMARY OUTCOMES: pain recorded by numerical rating scale (NRS). SECONDARY OUTCOMES: hip flexion and internal rotation ROM, and physical performance (timed up and go, sit to stand, and 40 m self placed walk test) were assessed before and after the intervention. RESULTS: For the MWM group, pain decreased by 2 points on the NRS, hip flexion increased by 12.2 degrees , internal rotation by 4.4 degrees , and functional tests were also improved with clinically relevant effects following the MWM. There were no significant changes in the sham group for any outcome variable. CONCLUSIONS: Pain, hip flexion ROM and physical performance immediately improved after the application of MWM in elderly patients suffering hip OA. The observed immediate changes were of clinical relevance. Future studies are required to determine the long-term effects of this intervention. PMID- 26559320 TI - Letter to the Editor regarding "Reliability and validity of non-radiographic methods of thoracic kyphosis measurement: A systematic review". PMID- 26559322 TI - Omalizumab reduces cysteinyl leukotriene and 9alpha,11beta-prostaglandin F2 overproduction in aspirin-exacerbated respiratory disease. PMID- 26559321 TI - Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy. AB - BACKGROUND: Specific immunotherapy (SIT) is the only treatment with proved long term curative potential in patients with allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B-cell repertoires are not well understood. OBJECTIVE: We sought to characterize the IgE sequences expressed by allergen-specific B cells and track the fate of these B-cell clones during SIT. METHODS: We used high-throughput antibody gene sequencing and identification of allergen-specific IgE with combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and the nasal mucosa from aeroallergen-sensitized subjects before and during the first year of subcutaneous SIT. RESULTS: Of 52 distinct allergen-specific IgE heavy chains from 8 allergic donors, 37 were also detected by using high-throughput antibody gene sequencing of blood samples, nasal mucosal samples, or both. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. CONCLUSION: In the future, combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies might aid assessment of SIT mechanisms and efficacy. PMID- 26559324 TI - A challenging undertaking: Stem cell transplantation for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. PMID- 26559323 TI - Fold stability during endolysosomal acidification is a key factor for allergenicity and immunogenicity of the major birch pollen allergen. AB - BACKGROUND: The search for intrinsic factors, which account for a protein's capability to act as an allergen, is ongoing. Fold stability has been identified as a molecular feature that affects processing and presentation, thereby influencing an antigen's immunologic properties. OBJECTIVE: We assessed how changes in fold stability modulate the immunogenicity and sensitization capacity of the major birch pollen allergen Bet v 1. METHODS: By exploiting an exhaustive virtual mutation screening, we generated mutants of the prototype allergen Bet v 1 with enhanced thermal and chemical stability and rigidity. Structural changes were analyzed by means of x-ray crystallography, nuclear magnetic resonance, and molecular dynamics simulations. Stability was monitored by using differential scanning calorimetry, circular dichroism, and Fourier transform infrared spectroscopy. Endolysosomal degradation was simulated in vitro by using the microsomal fraction of JAWS II cells, followed by liquid chromatography coupled to mass spectrometry. Immunologic properties were characterized in vitro by using a human T-cell line specific for the immunodominant epitope of Bet v 1 and in vivo in an adjuvant-free BALB/c mouse model. RESULTS: Fold stabilization of Bet v 1 was pH dependent and resulted in resistance to endosomal degradation at a pH of 5 or greater, affecting presentation of the immunodominant T-cell epitope in vitro. These properties translated in vivo into a strong allergy-promoting TH2 type immune response. Efficient TH2 cell activation required both an increased stability at the pH of the early endosome and efficient degradation at lower pH in the late endosomal/lysosomal compartment. CONCLUSIONS: Our data indicate that differential pH-dependent fold stability along endosomal maturation is an essential protein-inherent determinant of allergenicity. PMID- 26559326 TI - Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. PMID- 26559325 TI - Inhibition of IgE-mediated allergic reactions by pharmacologically targeting the circadian clock. AB - BACKGROUND: The circadian clock temporally gates signaling through the high affinity IgE receptor (FcepsilonRI) in mast cells, thereby generating a marked day/night variation in allergic reactions. Thus manipulation of the molecular clock in mast cells might have therapeutic potential for IgE-mediated allergic reactions. OBJECTIVE: We determined whether pharmacologically resetting the molecular clock in mast cells or basophils to times when FcepsilonRI signaling was reduced (ie, when core circadian protein period 2 [PER2] is upregulated) resulted in suppression of IgE-mediated allergic reactions. METHODS: We examined the effects of PF670462, a selective inhibitor of the key clock component casein kinase 1delta/epsilon, or glucocorticoid, both of which upregulated PER2 in mast cells, on IgE-mediated allergic reactions both in vitro and in vivo. RESULTS: PF670462 or corticosterone (or dexamethasone) suppressed IgE-mediated allergic reactions in mouse bone marrow-derived mast cells or basophils and passive cutaneous anaphylactic reactions in mice in association with increased PER2 levels in mast cells or basophils. PF670462 or dexamethasone also ameliorated allergic symptoms in a mouse model of allergic rhinitis and downregulated allergen-specific basophil reactivity in patients with allergic rhinitis. CONCLUSION: Pharmacologically resetting the molecular clock in mast cells or basophils to times when FcepsilonRI signaling is reduced can inhibit IgE-mediated allergic reactions. The results suggest a new strategy for controlling IgE mediated allergic diseases. Additionally, this study suggests a novel mechanism underlying the antiallergic actions of glucocorticoids that relies on the circadian clock, which might provide a novel insight into the pharmacology of this drug in allergic patients. PMID- 26559327 TI - Ocean acidification and global warming impair shark hunting behaviour and growth. AB - Alterations in predation pressure can have large effects on trophically structured systems. Modification of predator behaviour via ocean warming has been assessed by laboratory experimentation and metabolic theory. However, the influence of ocean acidification with ocean warming remains largely unexplored for mesopredators, including experimental assessments that incorporate key components of the assemblages in which animals naturally live. We employ a combination of long-term laboratory and mesocosm experiments containing natural prey and habitat to assess how warming and acidification affect the development, growth, and hunting behaviour in sharks. Although embryonic development was faster due to temperature, elevated temperature and CO2 had detrimental effects on sharks by not only increasing energetic demands, but also by decreasing metabolic efficiency and reducing their ability to locate food through olfaction. The combination of these effects led to considerable reductions in growth rates of sharks held in natural mesocosms with elevated CO2, either alone or in combination with higher temperature. Our results suggest a more complex reality for predators, where ocean acidification reduces their ability to effectively hunt and exert strong top-down control over food webs. PMID- 26559328 TI - Breastfeeding and childhood hospitalizations for asthma and other wheezing disorders. AB - PURPOSE: Observationally in Western settings, breastfeeding is associated with less childhood wheezing disorders but may be confounded by socioeconomic position. We examined the association of breastfeeding with asthma and other wheezing disorders in a developed non-Western setting with unique social patterning of breastfeeding. METHODS: Using Cox regression, we examined the adjusted associations of breastfeeding with public hospital admissions for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version. Clinical Modification: 466, 490, and 493) from 3 months to 12 years in a population-representative birth cohort of 8327 Hong Kong Chinese children. RESULTS: We did not find an association of exclusive breastfeeding for 3 months or more, compared with never breastfeeding, with hospitalization for asthma, bronchitis, and bronchiolitis to 12 years (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.63-1.25) nor for partial breastfeeding for any length of time or exclusive breastfeeding for less than 3 months (HR, 1.02; 95% CI, 0.86 1.21), adjusted for infant and parental characteristics and socioeconomic position. We also did not find an association of exclusive breastfeeding for 3 months or more with hospitalization for asthma only (International Classification of Diseases, Ninth Version. Clinical Modification: 493) (HR, 1.27; 95% CI, 0.82 1.98). CONCLUSIONS: In a large population-representative Chinese birth cohort, we did not find an association of breastfeeding with childhood hospitalizations for asthma and other wheezing disorders. PMID- 26559329 TI - Unmeasured confounding in pharmacoepidemiology. PMID- 26559331 TI - Weekend-weekday differences in diet among U.S. adults, 2003-2012. AB - PURPOSE: Dietary patterns differ by day of the week. This study examined weekend weekday differences in diet among U.S. adults. METHODS: Nationally representative data of 11,646 adults 18 years of age and above from the National Health and Nutrition Examination Survey 2003-2012 waves were analyzed. Individual fixed effect regressions were performed using data from two nonconsecutive 24-hour dietary recalls. RESULTS: Weekend diet was less healthful than weekday, with diet on Saturday the worst. Compared with weekday consumption, consumption on Saturday was associated with an increase in daily intakes of total energy by 181.04 kcal, energy from sugar-sweetened beverages 18.34 kcal, energy from alcohol 46.65 kcal, energy from discretionary foods 48.77 kcal, total fat 8.16 g, saturated fat 2.88 g, sugar 5.37 g, sodium 205.59 mg, and cholesterol 43.17 mg, a decrease in intakes of fruit by 13.90 g, vegetable 16.76 g, and fiber 0.67 g, a decrease in the Healthy Eating Index-2010 score by 2.32, and an increase in the prevalence of fast-food and full-service restaurant consumption by 10.21% and 17.79%, respectively. Weekend-weekday differences in diet varied by sex, age, race and/or ethnicity, education, income, and body weight status. CONCLUSIONS: Americans' weekend consumption was associated with increased calorie intake and poorer diet quality. PMID- 26559330 TI - Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis. AB - PURPOSE: To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. METHODS: We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. RESULTS: When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. CONCLUSIONS: Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. PMID- 26559332 TI - Species-specific duplications of NBS-encoding genes in Chinese chestnut (Castanea mollissima). AB - The disease resistance (R) genes play an important role in protecting plants from infection by diverse pathogens in the environment. The nucleotide-binding site (NBS)-leucine-rich repeat (LRR) class of genes is one of the largest R gene families. Chinese chestnut (Castanea mollissima) is resistant to Chestnut Blight Disease, but relatively little is known about the resistance mechanism. We identified 519 NBS-encoding genes, including 374 NBS-LRR genes and 145 NBS-only genes. The majority of Ka/Ks were less than 1, suggesting the purifying selection operated during the evolutionary history of NBS-encoding genes. A minority (4/34) of Ka/Ks in non-TIR gene families were greater than 1, showing that some genes were under positive selection pressure. Furthermore, Ks peaked at a range of 0.4 to 0.5, indicating that ancient duplications arose during the evolution. The relationship between Ka/Ks and Ks indicated greater selective pressure on the newer and older genes with the critical value of Ks = 0.4-0.5. Notably, species specific duplications were detected in NBS-encoding genes. In addition, the group of RPW8-NBS-encoding genes clustered together as an independent clade located at a relatively basal position in the phylogenetic tree. Many cis-acting elements related to plant defense responses were detected in promoters of NBS-encoding genes. PMID- 26559333 TI - Annual changes in seminal variables of golden lanchead pitvipers (Bothrops insularis) maintained in captivity. AB - Bothrops insularis is an endemic and critically endangered snake with an estimated population of 2000 individuals restricted to Queimada Grande Island, in southeastern Brazil. Brazilian researchers established a captive breeding program for the species that includes the application of assisted reproductive technologies. The present study, therefore, aimed to evaluate semen samples from captive B. insularis throughout the year to ascertain seasonal differences in semen traits as well as correlations with body size and weight. Eighteen males with snout-vent length (SVL) ranging from 43.5 to 73.7 cm were collected at quarterly basis between August 2012 and May 2013. Macroscopic analysis revealed semen volumes ranging from 0.5 to 6.0 MUL with samples featuring whitish to yellowish color and creamy and thick consistency. Viable sperm was obtained from all males indicating that individuals with SVL equal to or greater than 43.5 cm are sexually developed. However, adult and immature males (estimated by SVL) exhibited different seasonal profiles for motility and progressive motility. Adult males had a decrease in sperm motility and progressive motility during summer and spring, respectively, whereas the same variables did not vary throughout the year in immature snakes. Sperm concentration in all individuals was less (0.5 * 10(9) MUL) during the winter, but no seasonal fluctuations were detected in semen volume. These findings are of particular importance to the development of reproductive tools such as male selection, artificial insemination and sperm freezing for the genetic management of this critically endangered snake. PMID- 26559334 TI - Effects of Bel Canto Training on Acoustic and Aerodynamic Characteristics of the Singing Voice. AB - OBJECTIVES: This study was designed to assess the impact of 2 years of operatic training on acoustic and aerodynamic characteristics of the singing voice. STUDY DESIGN: This is a longitudinal study. METHODS: Participants were 21 graduate students and 16 undergraduate students. They completed a variety of tasks, including laryngeal videostroboscopy, audio recording of pitch range, and singing of syllable trains at full voice in chest, passaggio, and head registers. Inspiration, intraoral pressure, airflow, and sound pressure level (SPL) were captured during the syllable productions. RESULTS: Both graduate and undergraduate students significantly increased semitone range and SPL. The contributions to increased SPL were typically increased inspiration, increased airflow, and reduced laryngeal resistance, although there were individual differences. Two graduate students increased SPL without increased airflow and likely used supraglottal strategies to do so. CONCLUSIONS: Students demonstrated improvements in both acoustic and aerodynamic components of singing. Increasing SPL primarily through respiratory drive is a healthy strategy and results from intensive training. PMID- 26559335 TI - The influence of non-DNA-targeted effects on carbon ion-induced low-dose hyper radiosensitivity in MRC-5 cells. AB - Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion-induced LDHRS. PMID- 26559337 TI - Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films. AB - The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a sigmapi - d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of -4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials. PMID- 26559336 TI - Cost effectiveness of a mail-delivered individually tailored physical activity intervention for Latinas vs. a mailed contact control. AB - BACKGROUND: Physical inactivity is high in Latinas, as are chronic health conditions. There is a need for physical activity (PA) interventions that are not only effective but have potential for cost-effective widespread dissemination. The purpose of this paper was to assess the costs and cost effectiveness of a Spanish-language print-based mail-delivered PA intervention that was linguistically and culturally adapted for Latinas. METHODS: Adult Latinas (N = 266) were randomly assigned to receive mail-delivered individually tailored intervention materials or wellness information mailed on the same schedule (control). PA was assessed at baseline, six months (post-intervention) and 12 months (maintenance phase) using the 7-Day Physical Activity Recall Interview. Costs were calculated from a payer perspective, and included personnel time (wage, fringe, and overhead), materials, equipment, software, and postage costs. RESULTS: At six months, the PA intervention cost $29/person/month, compared to $15/person/month for wellness control. These costs fell to $17 and $9 at 12 months, respectively. Intervention participants increased their PA by an average of 72 min/week at six months and 94 min/week at 12 months, while wellness control participants increased their PA by an average of 30 min/week and 40 min/week, respectively. At six months, each minute increase in PA cost $0.18 in the intervention group compared to $0.23 in wellness control, which fell to $0.07 and $0.08 at 12 months, respectively. The incremental cost per increase in physical activity associated with the intervention was $0.15 at 6 months and $0.05 at 12 months. CONCLUSIONS: While the intervention was more costly than the wellness control, costs per minute of increase in PA were lower in the intervention. The print-based mail-delivered format has potential for broad, cost-effective dissemination, which could help address disparities in this at-risk population. TRIAL REGISTRATION: NCT01583140; Date of Registration: 03/06/2012; Funding Source of Trial: National Institute of Nursing Research (NINR); Name of Institutional Review Board: Brown University IRB; Date of Approval: 05/19/2009. PMID- 26559341 TI - Skin Autotomization and Regeneration--The African Spiny Mouse. PMID- 26559338 TI - Involvement of the extrinsic and intrinsic pathways in ultraviolet B-induced apoptosis of corneal epithelial cells. AB - The goal of this study was to elucidate the pathway by which UVB initiates efflux of K(+) and subsequently apoptosis in human corneal limbal epithelial (HCLE) cells. The initial focus of the study was on the extrinsic pathway involving Fas. HCLE cells transfected with Fas siRNA were exposed to 80-150 mJ/cm(2) UVB and incubated in culture medium with 5.5 mM K(+). Knockdown of Fas resulted in limited reduction in UVB-induced caspase-8 and -3 activity. Patch-clamp recordings showed no difference in UVB-induced normalized K(+) currents between Fas transfected and control cells. Knockdown of caspase-8 had no effect on the activation of caspase-3 following UVB exposure, while a caspase-8 inhibitor completely eliminated UVB activation of caspase-3. This suggests that caspase-8 is a robust enzyme, able to activate caspase-3 via residual caspase-8 present after knockdown, and that caspase-8 is directly involved in the UVB activation of caspase-3. Inhibition of caspase-9 significantly decreased the activation of caspases-8 and -3 in response to UVB. Knockdown of Apaf-1, required for activation of caspase-9, resulted in a significant reduction in UVB-induced activation of caspases-9, -8, and -3. Knockdown of Apaf-1 also inhibited intrinsic and UVB-induced levels of apoptosis, as determined by DNA fragmentation measured by TUNEL assay. In UVB exposed cultures treated with caspase-3 inhibitor, the percentage of apoptotic cells was reduced to control levels, confirming the necessity of caspase-3 activation in DNA fragmentation. The lack of effect of Fas knockdown on K(+) channel activation, as well as the limited effect on activation of caspases-8 and -3, strongly suggest that Fas and the extrinsic pathway is not of primary importance in the initiation of apoptosis in response to UVB in HCLE cells. Inhibition of caspase-8 and -3 activation following inhibition of caspase-9, as well as reduction in activation of caspases 9, -8, and -3 and DNA fragmentation in response to Apaf-1 knockdown support the conclusion that the intrinsic pathway is more important in UVB-induced apoptosis in HCLE cells. PMID- 26559342 TI - The Nevus in Literature--More Than a Mark. PMID- 26559343 TI - Streaks of White Hair in Popular Culture: Not as Simple as Black and White. PMID- 26559344 TI - Victorian Vampires Validated--The Similarities Between a Legendary Creature and a Dermatologic Pathology. PMID- 26559345 TI - Dermatologic Etymology: Configuration. PMID- 26559346 TI - Conrad Jobst: Great Inventor and Stocking Maker. PMID- 26559347 TI - Concerns About Presence of a Wild-Type BAP1 Allele in Absence of Nuclear Protein Expression. PMID- 26559348 TI - Concerns About Presence of a Wild-Type BAP1 Allele in Absence of Nuclear Protein Expression-Reply. PMID- 26559349 TI - Progressive transcortical sensory aphasia and progressive ideational apraxia owing to temporoparietal cortical atrophy. AB - BACKGROUND: In contrast to frontotemporal lobar degeneration, atrophy of the focal posterior lateral cortex has not been thoroughly studied. Three clinical types of focal cortical atrophy have been described: 1) logopenic variant of primary progressive aphasia, which presents with impaired repetition despite normal articulation; 2) posterior cortical atrophy, which presents with prominent visuospatial deficits; and 3) primary progressive apraxia. All three clinical types are characterized by specific patterns of hypometabolism/hypoperfusion: the left posterior perisylvian area in the logopenic variant of primary progressive aphasia, bilateral parietooccipital areas in posterior cortical atrophy, and the parietal cortex in primary progressive apraxia. However, not every patient clearly fits into one of these categories. CASE PRESENTATION: Here we describe two patients with atypical focal cortical presentations. They presented with a history of a few years of progressive transcortical sensory aphasia characterized by fluent output with normal grammar and syntax, normal repetition, sentence comprehension deficits, and anomia without loss of word meaning. They also presented with progressive apraxia that began at the initial stages. Some forms of posterior symptoms including acalculia, agraphia, and visuospatial deficits were also observed. Hypoperfusion was noted mainly in the left temporoparietal region, which is slightly posterior to the perisylvian area. CONCLUSIONS: Although our cases lack in CSF findings and PIB scan, these two cases and previous reports might suggest the existence of a subgroup of patients presenting with transcortical sensory aphasia, apraxia, and posterior symptoms (acalculia, agraphia, and visuospatial deficits) in the setting of Alzheimer's disease. This subgroup may reflect the spectrum of clinical manifestations between logopenic variant of primary progressive aphasia and posterior cortical atrophy. PMID- 26559351 TI - A competency-based approach to nurses' continuing education for clinical reasoning and leadership through reflective practice in a care situation. AB - Newly graduated nurses need to demonstrate high levels of competencies when they enter the workplace. A competency-based approach to their education is recommended to ensure patients' needs are met. A continuing education intervention consistent with the competency-based approach to education was designed and implemented in eight care units in two teaching hospitals. It consists of a series of 30-min reflective practice groups on clinical events that newly graduated nurses encountered in their practice. It was evaluated using a descriptive longitudinal evaluative research design, combining individual and group interviews with stakeholders, the analysis of facilitators' journal entries, and a research assistant's field notes. The results suggest that issues associated with the implementation of the continuing education intervention revolved around leadership for managers, flexibility for nursing staff, and role shifting for the facilitators. Newly graduated nurses who participated in the study noted that the reflective practice sessions contributed to the development of both clinical reasoning and leadership. Nursing managers stated the advantages of the intervention on nurses' professional development and for the quality and safety of care. Following the end of the study, participants from two units managed to pursue the activity during their work time. PMID- 26559350 TI - Performance of noninvasive ventilation in acute respiratory failure in critically ill patients: a prospective, observational, cohort study. AB - BACKGROUND: Noninvasive ventilation (NIV) is used in critically ill patients with acute respiratory failure (ARF) to avoid endotracheal intubation. However, the impact of NIV use on ARF patient's outcomes is still unclear. Our objectives were to evaluate the rate of NIV failure in hypoxemic patients with an arterial carbon dioxide partial pressure (PaCO2) < 45 mmHg or >= 45 mmHg at ICU admission, the predictors of NIV failure, ICU and hospital length of stay and 28-day mortality. METHODS: Prospective single center cohort study. All consecutive patients admitted to a mixed ICU during a three-month period who received NIV, except for palliative care purposes, were included in this study. Demographic data, APACHE II score, cause of ARF, number of patients that received NIV, incidence of NIV failure, length of ICU, hospital stay and mortality rate were compared between NIV failure and success groups. RESULTS: Eighty-five from 462 patients (18.4 %) received NIV and 26/85 (30.6 %) required invasive mechanical ventilation. NIV failure patients were comparatively younger (67 +/- 21 vs. 77 +/- 14 years; p = 0.031), had lower arterial bicarbonate (p = 0.005), lower PaCO2 levels (p = 0.032), higher arterial lactate levels (p = 0.046) and APACHE II score (p = 0.034) compared to NIV success patients. NIV failure occurred in 25.0 % of patients with PaCO2 >= 45 mmHg and in 33.3 % of patients with PaCO2 < 45 mmHg (p = 0.435). NIV failure was associated with an increased risk of in-hospital death (OR 4.64, 95 % CI 1.52 to 14.18; p = 0.007) and length [median (IQR)] of ICU [12 days (8-31) vs. 2 days (1-4); p < 0.001] and hospital [30 (19-42) vs. 15 (9-33) days; p = 0.010] stay. Predictors of NIV failure included age (OR 0.96, 95 % CI 0.93 to 0.99; p = 0.007) and APACHE II score (OR 1.13, 95 % CI 1.02 to 1.25; p = 0.018). CONCLUSION: NIV failure was associated with an increased risk of in hospital death, ICU and hospital stay and was not affected by baseline PaCO2 levels. Patients that failed were comparatively younger and had higher APACHE II score, suggesting the need for a careful selection of patients that might benefit from NIV. A well-designed study on the impact of a short monitored NIV trial on outcomes is needed. PMID- 26559352 TI - Long-term follow-up of trauma patients before and after implementation of a physician-staffed helicopter: A prospective observational study. AB - INTRODUCTION: The first Danish Helicopter Emergency Medical Service (HEMS) was introduced May 1st 2010. The implementation was associated with lower 30-day mortality in severely injured patients. The aim of this study was to assess the long-term effects of HEMS on labour market affiliation and mortality of trauma patients. METHODS: Prospective, observational study with a maximum follow-up time of 4.5 years. Trauma patients from a 5-month period prior to the implementation of HEMS (pre-HEMS) were compared with patients from the first 12 months after implementation (post-HEMS). All analyses were adjusted for sex, age and Injury Severity Score. RESULTS: Of the total 1994 patients, 1790 were eligible for mortality analyses and 1172 (n=297 pre-HEMS and n=875 post-HEMS) for labour market analyses. Incidence rates of involuntary early retirement or death were 2.40 per 100 person-years pre-HEMS and 2.00 post-HEMS; corresponding to a hazard ratio (HR) of 0.72 (95% confidence interval (CI) 0.44-1.17; p=0.18). The HR of involuntary early retirement was 0.79 (95% CI 0.44-1.43; p=0.43). The prevalence of reduced work ability after three years were 21.4% vs. 17.7%, odds ratio (OR)=0.78 (CI 0.53-1.14; p=0.20). The proportions of patients on social transfer payments at least half the time during the three-year period were 30.5% vs. 23.4%, OR=0.68 (CI 0.49-0.96; p=0.03). HR for mortality was 0.92 (CI 0.62-1.35; p=0.66). CONCLUSIONS: The implementation of HEMS was associated with a significant reduction in time on social transfer payments. No significant differences were found in involuntary early retirement rate, long-term mortality, or work ability. PMID- 26559353 TI - Drink-driving: India slow on enforcement. PMID- 26559355 TI - Haloimpatiens lingqiaonensis gen. nov., sp. nov., an anaerobic bacterium isolated from paper-mill wastewater. AB - An anaerobic bacterium, strain ZC-CMC3T, was isolated from a wastewater sample in Zhejiang, China. Cells were Gram-stain-positive, peritrichous, non-spore-forming, rod-shaped (0.6-1.2 * 2.9-5.1 MUm) and catalase- and oxidase-negative. Strain ZC CMC3T was able to grow at 25-48 degrees C (optimum 43 degrees C) and pH 5.5-8.0 (optimum pH 7.0). The NaCl concentration range for growth was 0-3 % (w/v) (optimum 0 %). The major polar lipids of the isolate were diphosphatidylglycerol, phosphatidylglycerol, several phospholipids and glycolipids. Main fermentation products from PYG medium were formate, acetate, lactate and ethanol. Substrates which could be utilized were peptone, tryptone, yeast extract and beef extract. No respiratory quinone was detected. The main fatty acids were C14 : 0, C16 : 0, C16 : 1cis 7 and C16 : 1cis 9. The DNA G+C content was 30.0 mol%. 16S rRNA gene sequence analysis revealed that the isolate belonged to the family Clostridiaceae. Phylogenetically, the most closely related species were Oceanirhabdus sediminicola NH-JN4T (92.8 % 16S rRNA gene sequence similarity) and Clostridium tepidiprofundi SG 508T (92.6 %). On the basis of phylogenetic, chemotaxonomic and phenotypic characteristics, strain ZC-CMC3T represents a novel species of a new genus in the family Clostridiaceae, for which the name Haloimpatiens lingqiaonensis gen. nov., sp. nov. is proposed. The type strain of the type species is ZC-CMC3T ( = KCTC 15321T = JCM 19210T = CCTCC AB 2013104T). PMID- 26559354 TI - Does extreme asymmetric dominance promote hybridization between Anopheles coluzzii and Anopheles gambiae s.s. in seasonal malaria mosquito communities of West Africa? AB - BACKGROUND: Anopheles gambiae s.s. and An. coluzzii are two of the most important malaria vector species in sub-Saharan Africa. These recently-diverged sibling species do not exhibit intrinsic post-zygotic barriers to reproduction and are thought to be separated by strong assortative mating combined with selection against hybrids. At present, little is known about the ecological conditions that determine hybridization and introgression between these cryptic taxa. METHODS: Swarm segregation and assortative mating were studied in Western Burkina Faso in the villages of Vallee du Kou (VK7) and Soumousso which differed in terms of which sibling species was much rarer than the other, and in Bana where both occurred in similar proportions. Swarms and pairs in copula were collected and genotyped, the proportion of intra and interspecific mating determined, and interspecific sperm transfer checked genetically. Females were collected through larval and adult indoor collections and genotyped or sexed-and-genotyped via a novel multiplex PCR. RESULTS: A total of 3,687 males and 220 females were collected and genotyped from 109 swarms. Only 3 swarms were composed of males from both species, and these were from the village of VK7 where An. gambiae s.s. was comparatively rare. Mixed-species pairs captured in copula were only detected in that area and made for 3.62 % and 100 % of mating pairs involving An. coluzzii and An. gambiae s.s. individuals, respectively. The high An. gambiae s.s. cross mating rate was mirrored by high rates of hybridizations estimated from female larvae and adults indoor collections. This contrasted with Soumousso, where despite being much less common than An. gambiae s.s., An. coluzzii males did not form mixed swarms, females were not found in interspecific swarms or copula and hybridization rates were low in both sibling species. CONCLUSIONS: These data suggest that ecological conditions leading to rare An. gambiae s.s. in populations dominated by An. coluzzii may promote a breakdown of spatial swarm segregation and assortative mating between the two species. The lower overall hybridization rates observed at the larval and adult indoor stages compared to cross-mating rates support the idea that post-mating selection processes acting against hybrids may occur mostly prior to and/or at the early larval stages. PMID- 26559356 TI - Cell mechanosensory recognizes ligand compliance at biomaterial interface. AB - Cells activate signalling through ligand-receptor bonds by sensing the mechanical properties of the surrounding extracellular matrix (ECM). Ligands, indeed, have to withstand the pulling force elicited by cell receptors through focal adhesions (FAs). On this basis, we developed functional ligands to be simply adsorbed on surfaces and constituted by a two-domain peptide: one derived from ECM proteins and available to receptors to offer biochemical cues, and another adsorbed on material to withstand the tension upon receptor engagement. Tuneable compliance of the anchoring domain of the peptide ligand was verified by single peptide analysis through molecular dynamics and adsorption measurements. We showed that the highest adsorbed peptides combined with integrin cell-binding motifs allow for the cell recognition and polarization with larger mature FA areas. On the contrary, the lowest adsorbed sequences did not provide mechanical resistance to the integrin pulling action, leading to more rounded cells with smaller FA areas. This evidence demonstrates that cell mechanosensory can discriminate ligands on surfaces and should be considered as a criterion in ligand design for material bioactivation. PMID- 26559357 TI - Novel antioxidative nanotherapeutics in a rat periodontitis model: Reactive oxygen species scavenging by redox injectable gel suppresses alveolar bone resorption. AB - The excessive production of reactive oxygen species (ROS) has been implicated in a variety of disorders, but to date, ROS scavengers have not been widely used for local treatment of inflammation, because they are rapidly eliminated from the inflamed site. We have designed a novel redox injectable gel (RIG) that is formed at 37 degrees C after disintegration of nano-assembled flower micelles allowing nitroxide radicals to act locally as specific ROS scavengers for the treatment of periodontitis. In the present study, we have confirmed retention of the RIG in the periodontal region, along with its antioxidant-related anti-inflammatory effects, and we have subsequently evaluated the inhibitory effect of the RIG against Porphyromonas gingivalis (P. gingivalis)-induced alveolar bone loss attributed to ROS. Alveolar bone loss was estimated by morphometry, gingival blood flow was measured using laser Doppler flowmetry, and osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase staining. The results show that the RIG can inhibit P. gingivalis-induced bone loss by antioxidant-related anti-inflammatory actions, and this suggests that the RIG is a promising novel therapeutic agent for the treatment of P. gingivalis-induced periodontitis. PMID- 26559358 TI - Integrative medicine, or not integrative medicine: that is the question. AB - On September 26-27, 2015, the 8th European Congress for Integrative Medicine convened the Global Summit on Integrative Medicine and Healthcare in Greater Copenhagen and Helsingor, Denmark at the Culture Yard just across from Kronborg Castle, which is home to William Shakespeare's Hamlet. This article is a summary of the author's presentation about integrative medicine within the Nordic region, driving factors that determine value in healthcare, key tenets of integrative medicine that lead to healthcare cost savings and the potential for a Nordic healthcare renaissance. PMID- 26559359 TI - Integrating traditional Chinese medicine into mainstream healthcare system in Hong Kong, China-A model of integrative medicine in the HKU-SZ Hospital. AB - The European Congress for Integrative Medicine 2015 Global Summit on Integrative Medicine and Healthcare in Greater Copenhagen has successfully promoted integrative medicine to the public once again. Integrative medicine, which is called the art and science of healthcare by Nordic Integrative Medicine, has been widely used in the world. In Hong Kong, integrated traditional Chinese and Western medicine, which is also known as the Chinese version of integrative medicine, provides a valuable reference for the development of integrative medicine in the world. In this article, we introduce the development of traditional Chinese medicine in Hong Kong and an integrated traditional Chinese and Western medicine model in the University of Hong Kong-Shenzhen Hospital. PMID- 26559360 TI - The evolution of integrative medical education: the influence of the University of Arizona Center for Integrative Medicine. AB - The University of Arizona Center for Integrative Medicine (AzCIM) was founded in 1994 with a primary focus of educating physicians in integrative medicine (IM). Twenty years later, IM has become an internationally recognized movement in medicine. With 40% of United States' medical schools having membership in the Academic Consortium for Integrative Medicine and Health it is foreseeable that all medical students and residents will soon receive training in the principles and practices of IM. The AzCIM has the broadest range and depth of IM educational programs and has had a major influence on integrative medical education in the United States. This review describes the fellowship, residency and medical student programs at AzCIM as well as other significant national drivers of IM education; it also points out the challenges faced in developing IM initiatives. The field of IM has matured with new national board certification in IM requiring fellowship training. Allied health professional IM educational courses, as well as integrative health coaching, assure that all members of the health care team can receive training. This review describes the evolution of IM education and will be helpful to academic centers, health care institutions, and countries seeking to introduce IM initiatives. PMID- 26559361 TI - The use of Chinese herbal drugs in Islamic medicine. AB - This paper investigates some of the ways that Chinese medicine has been transferred to the Western world and to Islamic territories. During the Golden Age of Islam (8th to 13th century CE), the herbal drug trade promoted significant commercial and scientific exchange between China and the Muslim world. Chinese herbal drugs have been described by medieval Muslim medical scholars such as Tabari (870 CE), Rhazes (925 CE), Haly Abbas (982 CE), Avicenna (1037 CE) and Jurjani (1137 CE). The term al-sin (the Arabic word for China) is used 46 times in Avicenna's Canon of Medicine in reference to herbal drugs imported from China. Cinnamon (dar sini; "Chinese herb"), wild ginger (asaron), rhubarb (rivand-e sini), nutmeg (basbasa), incense tree wood (ood), cubeb (kababe) and sandalwood (sandal) were the most frequently mentioned Chinese herbs in Islamic medical books. There are also multiple similarities between the clinical uses of these herbs in both medical systems. It appears that Chinese herbal drugs were a major component of the exchange of goods and knowledge between China and the Islamic and later to the Western world amid this era. PMID- 26559362 TI - Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: a review. AB - In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium (butterfly ginger) and Alpinia purpurata (red ginger), are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro-pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers. PMID- 26559363 TI - The effect of acupuncture on mood and working memory in patients with depression and schizophrenia. AB - BACKGROUND: In patients with depression, as well as in patients with schizophrenia, both mood and working memory performance are often impaired. Both issues can only be addressed and improved with medication to some extent. OBJECTIVE: This study investigates the mood and the working memory performance in patients with depression or schizophrenia and whether acupuncture can improve these. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A pragmatic clinical trial design was used. The study was conducted in a psychiatric clinic. Fifty patients with depression and 50 with schizophrenia were randomly divided into an experimental and a waiting-list group. Additionally, 25 healthy control participants were included. Twelve weeks of individualized acupuncture treatment was used as the clinical intervention. MAIN OUTCOME MEASURES: All patients were tested before (T1) and after (T2) acupuncture treatment on a mood scale (Beck Depression Inventory-II, BDI-II), a simple working memory task (digit span), and a complex working memory task (letter-number sequencing); the healthy controls were tested at T1 only. RESULTS: Patients with depression scored worse than the others on the BDI-II, and patients with schizophrenia scored worse than the healthy controls. On the digit span, patients with schizophrenia did not differ from healthy controls whereas they scored worse of all on the letter-number sequencing. With respect to the acupuncture findings, first, the present study showed that the use of acupuncture to treat patients with schizophrenia was both practical and safe. Moreover, acupuncture had a positive effect on the BDI-II for the depression group, but acupuncture had no effect on the digit span and on the letter-number sequencing performance for the two clinical groups. CONCLUSION: The clinical improvement in patients with depression after acupuncture treatment was not accompanied by any significant change in a simple working memory task or in a more complex working memory task; the same was true for the patients with schizophrenia. TRIAL REGISTRATION: Dutch Trial Register NTR3132. PMID- 26559364 TI - Effects of wet-cupping on blood pressure in hypertensive patients: a randomized controlled trial. AB - BACKGROUND: Although cupping remains a popular treatment modality worldwide, its efficacy for most diseases, including hypertension, has not been scientifically evaluated. OBJECTIVE: We aimed to determine the efficacy of wet-cupping for high blood pressure, and the incidence of the procedure's side effects in the intervention group. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a randomized controlled trial conducted in the General Practice Department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between May 2013 and February 2014. There were two groups (40 participants each): intervention group undergoing wet-cupping (hijama) in addition to conventional hypertension treatment, and a control group undergoing only conventional hypertension treatment. Three wet-cupping sessions were performed every other day. MAIN OUTCOME MEASURE: The mean systolic and diastolic blood pressures were measured using a validated automatic sphygmomanometer. The follow-up period was 8 weeks. RESULTS: Wet-cupping provided an immediate reduction of systolic blood pressure. After 4 weeks of follow-up, the mean systolic blood pressure in the intervention group was 8.4 mmHg less than in the control group (P=0.046). After 8 weeks, there were no significant differences in blood pressures between the intervention and control groups. In this study, wet-cupping did not result in any serious side effects. CONCLUSION: Wet-cupping therapy is effective for reducing systolic blood pressure in hypertensive patients for up to 4 weeks, without serious side effects. Wet-cupping should be considered as a complementary hypertension treatment, and further studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01987583. PMID- 26559365 TI - Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro. AB - OBJECTIVE: Methylation-specific epigenetic process and gene expression profiles of HeLa cells treated with ultra-high dilutions (HDs) of two plant extracts, Hydrastis canadensis (HC-30) and Marsdenia condurango (Condu-30), diluted 1060 times, were analyzed against placebo 30C (Pl-30) for alterations in gene profiles linked to epigenetic modifications. METHODS: Separate groups of cells were subjected to treatment of Condu-30, HC-30, and Pl-30 prepared by serial dilutions and succussions. Global microarray data recorded on Affymetrix platform, using 25 mer probes were provided by iLifeDiscoveries, India. Slides were scanned with 3000 7G microarray scanner and raw data sets were extracted from Cel (raw intensity) files. Analyses of global microarray data profile, differential gene expression, fold change and clusters were made using GeneSpring GX12.5 software and standard normalization procedure. Before microarray study, concentration of RNA (ng/MUL), RIN value and rRNA ratio for all the samples were analysed by Agilant Bioanalyzer 2100. Reverse transcriptase polymerase chain reaction (RT PCR) and quantitative RT-PCR were done for analyzing SMAD-4 expression. Fluorescence-activated cell sorting study was further made to elucidate fate of cells at divisional stages. Methylation-specific restriction enzyme assay was conducted for ascertaining methylation status of DNA at specific sites. RESULTS: HDs of HC-30 and Condu-30 differentially altered methylation in specific regions of DNA and expression profiles of certain genes linked to carcinogenesis, as compared to Pl-30. Two separate cut sites were found in genomic DNA of untreated and placebo-treated HeLa cells when digested with McrBC, compared to a single cut observed in Condu-30-treated genomic DNA. SMAD-4 gene expression validated the expression pattern observed in microarray profile. Methylation-specific restriction enzyme assay elucidated differential epigenetic modifications in drug treated and control cells. CONCLUSION: HDs triggered epigenetic modifications and alterations in microarray gene expression profiles of many genes associated with carcinogenesis in HeLa cells in vitro. PMID- 26559366 TI - Attitudes of medical students toward the practice and teaching of integrative medicine. AB - The General Medical Council encourages the integration of complementary and alternative medicine (CAM) teaching into basic medical education. We wished to explore the attitudes of medical students to CAM and its inclusion in their undergraduate curriculum. Medical students were invited to complete the validated Integrative Medicine Attitude Questionnaire (IMAQ) and to state whether they considered it appropriate for them to learn about CAM in medical school. The questionnaire was completed by 308 students (65.8% response rate). CAM had been received by a majority of respondents and their families. Participants believed that doctors with knowledge of CAM provide better patient care and that it is desirable for physicians to exploit the placebo effect. Most students expressed the view that doctors should be able to answer patients' questions about herbal medicines. There was a belief that patients should be warned to avoid using supplements which have not undergone rigorous testing. Students who were current or previous users of CAM or whose family members used CAM had higher total IMAQ scores and openness subscale scores than those who did not report use of CAM. Two hundred and nine (68%) students expressed a desire to study CAM as part of their medical curriculum. This study reveals a positive attitude towards a holistic approach to patient care which embraces CAM. Medical students believe that integrative medicine should be taught in medical school. PMID- 26559367 TI - Health effects of natural spring waters: A protocol for systematic reviews with a regional case example. AB - BACKGROUND: Spring water therapies have been used since at least 1550 BC. Despite the growing body of evidence supporting these therapies for a range of conditions, including musculoskeletal, dermatological, respiratory and cardiovascular conditions, they do not currently form part of mainstream healthcare in many countries. The protocol established in this paper aims to support systematic reviews that examine the health outcomes associated with human exposure to regional spring waters, using the Australia and New Zealand context as a case study. METHODS/DESIGN: The protocol searches for studies in eight health/medical databases, searches three local health/medical journals, and includes forwards and backwards searching. Standard systematic review methods are used including: specifying pre-determined inclusion criteria and data management plans, appraising the studies for bias, and allocation to a hierarchy of evidence. DISCUSSION: The protocol supports a review and comprehensive synthesis of the current evidence regarding the health effects of natural spring water, and can be adapted for reviews in other regions. From this evidence, recommendations regarding practice and future research can be made on the therapeutic role of spring water. PMID- 26559368 TI - Defining Rates and Risk Factors for Readmissions Following Emergency General Surgery. AB - IMPORTANCE: Hospital readmission rates following surgery are increasingly being used as a marker of quality of care and are used in pay-for-performance metrics. To our knowledge, comprehensive data on readmissions to the initial hospital or a different hospital after emergency general surgery (EGS) procedures do not exist. OBJECTIVE: To define readmission rates and identify risk factors for readmission after common EGS procedures. DESIGN, SETTING, AND PARTICIPANTS: Patients undergoing EGS, as defined by the American Association for the Surgery of Trauma, were identified in the California State Inpatient Database (2007-2011) on January 15, 2015. Patients were 18 years and older. We identified the 5 most commonly performed EGS procedures in each of 11 EGS diagnosis groups. Patient demographics (sex, age, race/ethnicity, and insurance type) as well as Charlson Comorbidity Index score, length of stay, complications, and discharge disposition were collected. Factors associated with readmission were determined using multivariate logistic regression models analysis. MAIN OUTCOMES AND MEASURES: Thirty-day hospital readmission. RESULTS: Among 177,511 patients meeting inclusion criteria, 57.1% were white, 48.8% were privately insured, and most were 45 years and older (51.3%). Laparoscopic appendectomy (35.2%) and laparoscopic cholecystectomy (19.3%) were the most common procedures. The overall 30-day readmission rate was 5.91%. Readmission rates ranged from 4.1% (upper gastrointestinal) to 16.8% (cardiothoracic). Of readmitted patients, 16.8% were readmitted at a different hospital. Predictors of readmission included Charlson Comorbidity Index score of 2 or greater (adjusted odds ratio: 2.26 [95% CI, 2.14-2.39]), leaving against medical advice (adjusted odds ratio: 2.24 [95% CI, 1.89-2.66]), and public insurance (adjusted odds ratio: 1.55 [95% CI, 1.47-1.64]). The most common reasons for readmission were surgical site infections (16.9%), gastrointestinal complications (11.3%), and pulmonary complications (3.6%). CONCLUSIONS AND RELEVANCE: Readmission after EGS procedures is common and varies widely depending on patient factors and diagnosis categories. One in 5 readmitted patients will go to a different hospital, causing fragmentation of care and potentially obscuring the utility of readmission as a quality metric. Assisting socially vulnerable patients and reducing postoperative complications, including infections, are targets to reduce readmissions. PMID- 26559369 TI - Pressure-induced superconductivity in H2-containing hydride PbH4(H2)2. AB - High pressure structure, stability, metallization, and superconductivity of PbH4(H2)2, a H2-containing compound combining one of the heaviest elements with the lightest element, are investigated by the first-principles calculations. The metallic character is found over the whole studied pressure range, although PbH4(H2)2 is metastable and easily decompose at low pressure. The decomposition pressure point of 133 GPa is predicted above which PbH4(H2)2 is stable both thermodynamically and dynamically with the C2/m symmetry. Interestedly, all hydrogen atoms pairwise couple into H2 quasi-molecules and remain this style up to 400 GPa in the C2/m structure. At high-pressure, PbH4(H2)2 tends to form the Pb-H2 alloy. The superconductivity of Tc firstly rising and then falling is observed in the C2/m PbH4(H2)2. The maximum of Tc is about 107 K at 230 GPa. The softening of intermediate-frequency phonon induced by more inserted H2 molecules is the main origin of the high Tc. The results obtained represent a significant step toward the understanding of the high pressure behavior of metallic hydrogen and hydrogen-rich materials, which is helpful for obtaining the higher Tc. PMID- 26559370 TI - Faecal contamination of echinoderms: first report of heavy Escherichia coli loading of sea urchins from a natural growing area. AB - Although little evidence existed to support that view, European countries and in particular France, have regarded echinoderms, including sea urchins, as low risk in terms of feacal contamination. It is hypothesized that the sea urchins mode of feeding, which is based on grazing and differs from bivalve molluscs, would prevent it from concentrating high levels of Escherichia coli. Here, we monitored E. coli levels in sea urchins (Paracentrotus lividus) and in filter-feeder mussels (Mytillus galloprovincialis), collected concurrently from the same natural area over a 1-year period to verify this assumption. Sea urchins were collected on the seafloor, whereas mussels were collected from the water column at a depth of 4 m. Our results showed heavy bacterial loading of sea urchins in a natural growing environment. Moreover, we highlighted that E. coli contamination of sea urchins could, in certain conditions, be higher than those detected in filter-feeding mussels collected at the same location. Finally, the results showed a significant correlation between rainfall and E. coli concentrations in sea urchins, suggesting that the bacterial safety of sea urchin could be linked to the quality of the surrounding water. SIGNIFICANCE AND IMPACT OF THE STUDY: The European regulation requires competent authorities to monitor the sanitary status of shellfish, including live echinoderms, through faecal indicator organisms. In the French Mediterranean, sea urchin production is significant. Until now, as no data showed significant E. coli contamination levels, no monitoring programs focused on this species. This study demonstrates that sea urchins are more vulnerable to faecal contamination than previously hypothesized, especially during heavy rainfall. In consequence, the European authority general approach to microbiological management of shellfish should be applied to sea urchins. PMID- 26559371 TI - Development of a new system for guidewire-assisted tracheal intubation: manikin and cadaver evaluation. AB - Guided intubation using a tracheal tube and semi-rigid introducer is associated with technical difficulties, failure and traumatic complications. We describe the development of a new system of guidewire-assisted tracheal intubation that may circumvent these problems. A reinforced silicone tracheal tube was modified with a guide channel built inside its wall, and a nitinol non-kinking guidewire was matched to this channel. Both anterograde and retrograde tracheal intubation were evaluated in a test rig, an airway manikin and then in preserved and fresh cadavers. There was minimal resistance to passage of the guidewire through the guide channel when the modified tube was in an anatomical configuration, in contrast to moderate resistance when an Airway Exchange Catheter was passed through a PVC tracheal tube. Intubation using the new equipment required increased force in the manikin and preserved cadavers, but minimal force in fresh cadavers. Resistance to tracheal tube advancement in preserved cadavers was overcome by withdrawal followed by 90 degrees rotation, but this manoeuvre was not required in fresh cadavers. We suggest that the combination of the modified tracheal tube and matching guidewire may allow easy and reliable single-step guided tracheal intubation when used in patients. PMID- 26559372 TI - Obesity, socio-demographic and attitudinal factors associated with sugar sweetened beverage consumption: Australian evidence. AB - OBJECTIVE: To explore factors associated with sugar-sweetened beverage (SSB) consumption in Australia. METHODS: Pooled data from Western Australian (WA) and South Australian (SA) 2009 and 2012 nutrition monitoring survey series interviews of 2,832 WA and 10,764 SA adults aged 18 to 64 years. Demographic data were collected and independent samples t-test, analysis of variance, multiple logistic regression performed. RESULTS: Obese participants were more likely to consume SSB than healthy weight participants (SA: OR=1.77; 95% CI 1.56-2.02; WA: OR=1.53; 1.05-2.24). SA obese participants consumed more SSB per day (152.0 mL; 140.7 163.5) than healthy weight (80.1 mL; 73.2-88.2; p<0.001) and overweight participants (106.9 mL; 99.0, 114.8; p<0.001). Males were more likely to consume SSB than females (SA: OR 1.80; 1.35-2.40; WA: 1.81; 1.64-2.00). WA participants who didn't think about the healthiness of food (4.55; 2.71-7.64) and bought meals away from home the day prior (1.55; 1.15-2.09) were more likely to consume SSB. SA adults rating their health highest were less likely to consume SSB (0.62; 0.54 0.72). CONCLUSIONS: SSB consumers are more likely to be male, have little interest in health, or have purchased a meal away from home. IMPLICATIONS: Increasing awareness of the adverse health effects of consumption may be a first step in curbing SSB intake. PMID- 26559374 TI - A Survey of Spinal Cord Stimulator Use by Chronic Pain Patients While Driving. AB - OBJECTIVE: The study aims to assess utilization of spinal cord stimulator (SCS) devices while driving a vehicle and potential association with motor vehicle accidents (MVAs). MATERIALS AND METHODS: A telephone survey study was conducted in two phases, from 2001 to 2008 and from 2009 to 2011. Patients selected for the survey were age 18 or older and at least one year post-SCS implantation, demonstrating stable analgesic use for at least six months, and reporting a minimum of 50% pain relief and enhancement of activities of daily living. Both phases of the study evaluated for degree of utilization of SCS while driving a motor vehicle as well as associated accidents. Additionally, patients with active SCS use while driving were further asked in the second phase of the study about mileage per week and first activation of the device postimplant. RESULTS: Ninety seven percent of the 78 patients contacted were active drivers and of these, 80% reported chronic and consistent use of SCS for the analgesic benefit while operating a motor vehicle. Eleven percent reported MVAs, which were not related to SCS. In the second phase of the study, participants reported a median of 100 miles driven per week with the SCS device on and began use of the device at a median of 21 days postimplant for up to 49 months. CONCLUSION: Because of the perceived benefits of pain reduction, there is high utilization of active SCS while driving a motor vehicle and that does not seem predispose toward MVAs. PMID- 26559373 TI - Constitutive activation of STAT3 in breast cancer cells: A review. AB - Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in numerous cancer types, including more than 40% of breast cancers. In contrast to tight regulation of STAT3 as a latent transcription factor in normal cells, its signaling in breast cancer oncogenesis is multifaceted. Signaling through the IL-6/JAK/STAT3 pathway initiated by the binding of IL-6 family of cytokines (i.e., IL-6 and IL-11) to their receptors have been implicated in breast cancer development. Receptors with intrinsic kinase activity such as EGFR and VEGFR directly or indirectly induce STAT3 activation in various breast cancer types. Aberrant STAT3 signaling promotes breast tumor progression through deregulation of the expression of downstream target genes which control proliferation (Bcl-2, Bcl-xL, Survivin, Cyclin D1, c-Myc and Mcl-1), angiogenesis (Hif1alpha and VEGF) and epithelial-mesenchymal transition (Vimentin, TWIST, MMP 9 and MMP-7). These multiple modes of STAT3 regulation therefore make it a central linking point for a multitude of signaling processes. Extensive efforts to target STAT3 activation in breast cancer had no remarkable success in the past because the highly interconnected nature of STAT3 signaling introduces lack of selectivity in pathway identification for STAT3 targeted molecular therapies or because its role in tumorigenesis may not be as critical as it was thought. This review provides a full spectrum of STAT3's involvement in breast cancer by consolidating the knowledge about its role in breast cancer development at multiple levels: its differential regulation by different receptor signaling pathways, its downstream target genes, and modification of its transcriptional activity by its coregulatory transcription factors. PMID- 26559375 TI - Nanoparticle Vesicles with Controllable Surface Topographies through Block Copolymer-Mediated Self-Assembly of Silica Nanospheres. AB - Silica nanoparticle vesicles (NPVs) with encapsulating capability and surface permeability are highly attractive in nanocatalysis, biosensing, and drug delivery systems. Herein, we report the facile fabrication of silica NPVs composed of a monolayer of silica nanospheres (SNSs, ca. 15 nm in diameter) through the block copolymer-mediated self-assembly of SNSs. The silica NPVs gain different surface topographies, such as raspberry- and brain coral-like topographies, under controlled heat treatment conditions. The vesicular assembly of SNSs is successful with a series of poly(propylene oxide)-poly(ethylene oxide) poly(propylene oxide) block copolymers, and the size of NPVs can be tuned by changing their molecular weight. The polymer is easily extracted from the NPVs with their colloidal dispersibility and structural integrity intact. The polymer free silica NPVs further serve as a reaction vessel and host for functional materials such as tin oxide nanoparticles. PMID- 26559376 TI - Serous Neoplasms of the Pancreas: A Clinicopathologic Analysis of 193 Cases and Literature Review With New Insights on Macrocystic and Solid Variants and Critical Reappraisal of So-called "Serous Cystadenocarcinoma". AB - The literature on "variants" and "malignant" counterparts of pancreatic serous cystic neoplasms (SCNs) is highly conflicted. Clinicopathologic characteristics of 193 SCNs were investigated, along with a critical literature review. For the macrocystic (oligocystic) variant, in this largest series, a demographic profile in contrast to current literature was elucidated, with 21% frequency, predominance in female individuals (4:1), body/tail location (1.7*), younger age of patients (mean age, 50 y), and frequent radiologic misdiagnosis as other megacystic neoplasms. Solid SCNs were rare (n=4, 2%) and often misinterpreted radiologically as neuroendocrine tumors. Available fine-needle aspiration in 11 cases was diagnostic in only 1. Radiologic impression was "malignancy" in 5%. Associated secondary tumors were detected in 13% of resections, mostly neuroendocrine. Secondary "infiltration" (direct adhesion/penetration) of spleen, stomach, colon, and/or adjacent nodes was seen in 6 (3%) fairly large SCNs (mean, 11 cm) with no distant metastasis. Three SCNs recurred locally, but completeness of original resection could not be verified. Our only hepatic SCN lacked a concurrent pancreatic tumor. Literature appraisal revealed that there are virtually no deaths that are directly attributable to dissemination/malignant behavior of SCNs, and most cases reported as "malignant" in fact would no longer fulfill the more recent World Health Organization criteria but instead would represent either (1) local adhesion/persistence of tumor, (2) cases with no histologic verification of malignancy, or (3) liver SCNs with benevolent behavior (likely representing multifocality, rather than true metastasis, especially considering there was no fatality related to this and no reported metastases to other remote sites). In conclusion, in contrast to the literature, the clinicopathologic characteristics of solid and macrocystic SCN variants are similar to their microcystic counterpart, although their radiologic diagnosis is challenging. Recurrence/secondary invasion of neighboring organs occurs rarely in larger SCNs but seems innocuous. An SCN should not be classified as "malignant" unless there is clear-cut evidence of histologic malignancy or documented distant metastasis. PMID- 26559378 TI - TTF-1 and Napsin-A Are Not Markers for Biliary Phenotype: An Immunohistochemical Study of Gallbladder Adenocarcinomas. PMID- 26559379 TI - Hereditary Renal Cell Carcinoma Syndromes: Clinical, Pathologic, and Genetic Features. AB - Renal cell carcinomas associated with syndromes of a heritable nature account for about 4% of all renal cell carcinomas. They are characterized by an earlier age of onset, and are often multicentric and bilateral. Some of these patients may fit into well-characterized kidney cancer syndromes, while many more may have a genetic component that is not fully recognized or understood. The presence of extrarenal clinical features may suggest a specific renal tumor susceptibility syndrome. Moreover, each syndrome is associated with specific renal pathology findings. Recognition of individuals and families with a high risk of renal neoplasia is important so that surveillance for renal tumors may be initiated. This manuscript reviews the clinical, pathological, and molecular features of hereditary renal cell carcinoma syndromes with emphasis on the morphologic features of these tumors and the molecular mechanisms of hereditary renal tumorigenesis. PMID- 26559377 TI - A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas. AB - International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas. PMID- 26559380 TI - The Influence of Unsportsmanlike Fouls on Basketball Teams' Performance According to Context-Related Variables. AB - The aim of the current study was to analyze the temporal effects that unsportsmanlike fouls may have on basketball teams' scoring performance under consideration of context-related variables. The authors analyzed 130 unsportsmanlike fouls from 362 elite basketball games (men's and women's Olympic Games, European and World Championships). The context-related variables studied were score-line, quality of opposition, timeout situation, minutes remaining, and player status. The data were analyzed with linear-regression models. The results showed that both teams (the team that made the foul and the opponent) had similar positive scoring performances during 1 and 3 ball possessions after the unsportsmanlike foul (short-term effect). However, 5 ball possessions after the foul (midterm effect), the team that made the foul had a scoring disadvantage ( 0.96) and the opponent team an advantage (0.78). The context-related variable quality of opposition was significant only during 1 ball possession, with negative effects for the team that made the foul and positive effects for the opponent. The final outcome showed a positive effect for score-line when the unsportsmanlike foul was made (0.96) and for quality of opposition (0.64). PMID- 26559381 TI - Confined Polymerization in Highly Ordered Mesoporous Organosilicas. AB - Hybrid mesoporous organosilica exhibiting crystal-like order in the walls provided an ideal channel reaction vessel for the confined polymerization of acrylonitrile (PAN). The resulting high-molecular-mass PAN fills the channels at high yield and forms an ordered nanostructure of polymer nanobundles enclosed into the hybrid matrix. The in situ thermal transformation of PAN into rigid polyconjugated and, eventually, into condensed polyaromatic carbon nanofibers, retains the periodic architecture. Simultaneously, the matrix evolves showing the fusion of the p-phenylene rings and the cleavage of carbon?silicon bonds: this gives rise to graphitic-carbon/silica nanocomposites containing hyper-oxydrylated silica nanophases. Interestingly, the 3D hexagonal mesostructure survives in the carbonaceous material. The exploitation of porous materials of high capacity and a hybrid nature, for polymerization in the confined state, followed by high temperature treatments, allowed us to achieve unique and precisely fabricated nanostructures, thus paving the way for the construction of fine-tuned electronic and light-harvesting materials. PMID- 26559382 TI - Anatomy of the Murine Hepatobiliary System: A Whole-Organ-Level Analysis Using a Transparency Method. AB - The biliary tract is a well-branched ductal structure that exhibits great variation in morphology among vertebrates. Its function is maintained by complex constructions of blood vessels, nerves, and smooth muscles, the so-called hepatobiliary system. Although the mouse (Mus musculus) has been used as a model organism for humans, the morphology of its hepatobiliary system has not been well documented at the topographical level, mostly because of its small size and complexity. To reconcile this, we conducted whole-mount anatomical descriptions of the murine extrahepatic biliary tracts with related blood vessels, nerves, and smooth muscles using a recently developed transparentizing method, CUBIC. Several major differences from humans were found in mice: (1) among the biliary arteries, the arteria gastrica sinistra accessoria was commonly found, which rarely appears in humans; (2) the sphincter muscle in the choledochoduodenal junction is unseparated from the duodenal muscle; (3) the pancreatic duct opens to the bile duct without any sphincter muscles because of its distance from the duodenum. This state is identical to a human congenital malformation, an anomalous arrangement of pancreaticobiliary ducts. However, other parts of the murine hepatobiliary system (such as the branching patterns of the biliary tract, blood vessels, and nerves) presented the same patterns as humans and other mammals topologically. Thus, the mouse is useful as an experimental model for studying the human hepatobiliary system. PMID- 26559383 TI - Transoral robotic surgery for early T classification hypopharyngeal cancer. AB - BACKGROUND: For hypopharyngeal cancer, transoral robotic surgery (TORS) has been reported as a new organ preserving treatment but outcomes are rarely reported. METHODS: From 2010 to 2013, 10 patients with early T classification pyriform sinus cancer were selected to receive TORS and conventional neck dissection. The clinical parameters, including rates of adjuvant radiotherapy, survivals, as well as organ and function preservation, were retrospectively analyzed. RESULTS: TORS was successful in all 10 patients, and 5 patients received adjuvant radiotherapy. After mean follow-up of 26 months, 1 patient died of distant metastasis and 1 patient died of other malignancy. There was no local recurrence and larynxes were all preserved. Eight surviving patients who were followed up continuously could receive oral intake and had a serviceable voice without tracheostomy or feeding tubes. CONCLUSION: TORS is a feasible transoral approach for selected patients with early T classification hypopharyngeal cancer. The reported oncologic/functional outcomes are satisfactory. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: 857-862, 2016. PMID- 26559384 TI - Causes of endogenous uveitis in cats presented to referral clinics in North Carolina. AB - OBJECTIVE: To investigate the causes of endogenous uveitis in cats presenting to referral ophthalmology clinics in North Carolina. PROCEDURE: Medical records of cats diagnosed with endogenous uveitis at North Carolina State University's College of Veterinary Medicine (NCSU-CVM) or Animal Eye Care Associates of Cary, NC between 2003 and 2015 were reviewed. Inclusion criteria were cats that had complete diagnostic workups, including clinical, clinicopathological, serological, and histopathological data, as well as imaging modalities. Serology was consistently completed for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), Toxoplasma gondii, and Bartonella spp. RESULTS: One hundred and twenty cats met the inclusion criteria. Seroprevalence of FeLV (2.7%), FIV (7.3%), FCoV (34.7%), T. gondii (23.7%), and Bartonella spp. (43.2%) was observed, with a combined seroprevalence of 59.2%. Nineteen cats (15.8%) were diagnosed with feline infectious peritonitis (FIP) based on clinical, hematological, serological, histopathological, and necropsy findings. The average age of all cases was 7.62 years, while the average age of cats diagnosed with FIP was 1.82 years. Neoplasia was diagnosed in six cats (5.0%). No underlying etiology was found in 49 cats (40.8%). CONCLUSIONS: Both idiopathic and neoplastic causes of uveitis were less prevalent than previously reported in studies, while seropositivity was higher than previously reported for the study area. This may be due to improved diagnostic capabilities or that cats with infectious disease were more likely to be referred. Because of the high prevalence of FIP, young cats with uveitis should be evaluated for hyperglobulinemia and FCoV serology should be performed as minimal diagnostics. PMID- 26559385 TI - Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS). AB - INTRODUCTION: Cross-sex hormone treatment of gender dysphoria (GD) patients changing from male to female a prerequisite for sex reassignment. For initial physical adaptation, a combined treatment of anti-androgens and estrogens is used. Provided that patients fulfill specific criteria, sex reassignment surgery (SRS) presents the final step toward physical adaptation. However, systematic studies analyzing effects of hormone treatment regimens are lacking. AIM: The aim of this study was to compare the effects of three different hormonal treatment strategies regarding endocrinological parameters and testicular histology. METHODS: Testicular tissues were obtained in a multicenter study from 108 patients on the day of SRS from three clinics following different treatment strategies. Patients either discontinued treatment 6 weeks (clinic A) or 2 weeks (clinic B) prior to SRS or not at all (clinic C). Testicular tissues, ethylenediaminetetraacetic acid blood and questionnaires were obtained on the day of SRS. MAIN OUTCOME MEASURES: Blood hormone and intratesticular testosterone (ITT) levels were measured. Testicular weight and histology were evaluated and the percentage of luteinizing hormone/choriogonadotropin receptor (LHCGR) positive cells was determined. RESULTS: According to the questionnaires, patients showed desired phenotypical changes including breast growth (75%) and smooth skin (32%). While patients from clinics A and B presented with rather virilized hormonal levels, patients from clinic C showed generally feminized blood serum levels. Histological evaluation revealed highly heterogeneous results with about 24% of patients presenting with qualitatively normal spermatogenesis. In accordance with serum endocrine profile, ITT levels were lowest in clinic C and correlated with testosterone and free testosterone, but not with the spermatogenic state. The percentage of LHCGR-positive cells and ITT levels did not correlate. CONCLUSION: Only patients that did not discontinue hormonal treatment showed feminized blood levels on the day of SRS. The ones who stopped re-virilized quickly. Interestingly, testicular histology was highly heterogeneous irrespective of the treatment strategy, a phenomenon that requires further investigation. PMID- 26559386 TI - Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years. AB - AIMS: The objective was to investigate the long-term all-cause mortality in patients aged 50-69 years after aortic valve replacement (AVR) with bioprosthetic or mechanical valves. METHODS AND RESULTS: All patients aged 50-69 years who had undergone AVR in Sweden 1997-2013 were identified from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register. Subsequent patient-level record linkage with national health-data registers provided patient characteristics, vital status, and clinical outcomes. Of the 4545 patients, 60% (2713/4545) had received mechanical valves and 40% (1832/4545) bioprostheses. In 1099 propensity score-matched patient pairs, 16% (180/1099) had died in the mechanical valve group and 20% (217/1099) in the bioprosthetic group; mean follow-up 6.6 (maximum 17.2) years. Survival was higher in the mechanical than in the bioprosthetic group: 5-, 10-, and 15-year survival 92, 79, and 59% vs. 89, 75, and 50%; hazard ratio 1.34; 95% confidence interval (CI) 1.09-1.66; P = 0.006. There was no difference in stroke [subdistribution hazard ratio (sHR) 1.04; 95% CI 0.72-1.50, P = 0.848]; however, the risk for aortic valve reoperation was higher (sHR 2.36; 95% CI 1.42-3.94, P = 0.001), and for major bleeding lower (sHR 0.49; 95% CI 0.34 0.70, P < 0.001), in patients who had received bioprostheses than in those with mechanical valves. CONCLUSION: Patients aged 50-69 years who received mechanical valves had better long-term survival after AVR than those with bioprostheses. The risk of stroke was similar; however, patients with bioprostheses had a higher risk of aortic valve reoperation and a lower risk of major bleeding. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/show/NCT02276950. CLINICALTRIALSGOV IDENTIFIER: NCT02276950. PMID- 26559387 TI - The Australian and New Zealand Intensive Care Research Centre. PMID- 26559388 TI - Comparative phylogeography of endemic Azorean arthropods. AB - BACKGROUND: For a remote oceanic archipelago of up to 8 Myr age, the Azores have a comparatively low level of endemism. We present an analysis of phylogeographic patterns of endemic Azorean island arthropods aimed at testing patterns of diversification in relation to the ontogeny of the archipelago, in order to distinguish between alternative models of evolutionary dynamics on islands. We collected individuals of six species (representing Araneae, Hemiptera and Coleoptera) from 16 forest fragments from 7 islands. Using three mtDNA markers, we analysed the distribution of genetic diversity within and between islands, inferred the differentiation time-frames and investigated the inter-island migration routes and colonization patterns. RESULTS: Each species exhibited very low levels of mtDNA divergence, both within and between islands. The two oldest islands were not strongly involved in the diffusion of genetic diversity within the archipelago. The most haplotype-rich islands varied according to species but the younger, central islands contributed the most to haplotype diversity. Colonization events both in concordance with and in contradiction to an inter island progression rule were inferred, while a non-intuitive pattern of colonization from western to eastern islands was also inferred. CONCLUSIONS: The geological development of the Azores has followed a less tidy progression compared to classic hotspot archipelagos, and this is reflected in our findings. The study species appear to have been differentiating within the Azores for <2 Myr, a fraction of the apparent life span of the archipelago, which may indicate that extinction events linked to active volcanism have played an important role. Assuming that after each extinction event, colonization was initiated from a nearby island hosting derived haplotypes, the apparent age of species diversification in the archipelago would be moved closer to the present after each extinction-recolonization cycle. Exploiting these ideas, we propose a general model for future testing. PMID- 26559389 TI - Immune therapy in autoimmune encephalitis: a systematic review. AB - We have reviewed the literature of immune therapy in autoimmune encephalitis associated with antibodies to cell surface antigens including N-methyl-D aspartate receptor (NMDAR), leucine-rich, glioma-inactivated protein-1 (LGI1), contactin-associated protein-2 (Caspr2), the alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid-A receptor (GABAAR), gamma-aminobutyric acid-B receptor (GABABR), Glycine R and other rarer antigens. Most studies are retrospective cohorts, and there are no randomised controlled trials. Most clinicians use first-line therapy (steroids, intravenous immunoglobulin, plasma exchange), and if severe or refractory, second-line therapy (rituximab, cyclophosphamide). When present, tumours should be removed. There are common therapeutic themes emerging. Firstly, patients given immune therapy do better and relapse less than patients given no treatment. Secondly, patients given early treatment do better. And thirdly, when patients fail first line therapy, second-line therapy improves outcomes and reduces relapses. Given the retrospective uncontrolled data, the literature has inherent bias, including severity and reporting bias. PMID- 26559390 TI - Selective in-plane nitrogen doping of graphene by an energy-controlled neutral beam. AB - Nitrogen-doped graphene promises to improve current electronic devices, sensors, and energy-based devices. To this end, the bonding states between carbon and nitrogen atoms can be manipulated to tailor the properties of the doped graphene. For example, graphitic nitrogen is known to promote desired catalytic activities in graphene fuel-cell systems, resulting from a four-electron reaction. However, established nitrogen-doping methods lack selectivity in dopant chemical identity and in dopant location; both are key factors in graphene property design because the properties depend on the chemical identity and location of the dopant. Here, we utilize a nitrogen neutral beam (NB) technique-with exquisite beam energy control-to dope graphene with nitrogen. Using x-ray photoelectron and Raman spectroscopy, we show that the energy of the nitrogen NB not only determines the chemistry of the nitrogen dopant introduced to graphene, but it also dictates the doping locations within graphene layers. PMID- 26559392 TI - Operating microscope with near infrared imaging function for indocyanine green lymphography in prevention of lymphedema with lymphaticovenous anastomosis immediately after mastectomy and axillary dissection. PMID- 26559391 TI - The role of ADAMTS-13 activity and complement mutational analysis in differentiating acute thrombotic microangiopathies. AB - ESSENTIALS: Molecular diagnostics has improved the differentiation of acute thrombotic microangiopathys (TMAs). Atypical hemolytic uremic syndrome may have features mimicking thrombotic thrombocytopenic purpura. We identified novel complement mutations and a high incidence of CD46, with favorable long term outcomes. Complement mutation analysis in TMA where the diagnosis is unclear and ADAMTS-13 activity is >10%. BACKGROUND: Differentiation of acute thrombotic microangiopathy (TMA) at presentation has historically been dependent on clinical parameters. Confirmation of thrombotic thrombocytopenic purpura (TTP) is increasingly reliant on demonstrating deficient ADAMTS-13 activity. The identification of alternative complement pathway abnormalities in atypical hemolytic uremic syndrome (aHUS), along with the proven efficacy of terminal complement inhibitors in treatment, has increased the need for rapid differentiation of TTP from aHUS. OBJECTIVES: We describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs. PATIENTS/METHODS: Fourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%. RESULTS: Of 14 aHUS patients, 11 (79%) had platelet counts < 30 * 10(9) /L during the acute phase. Median presenting creatinine level was 295 MUmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 MUmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported. CONCLUSIONS: We demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities. PMID- 26559393 TI - Successful pregnancy outcome under prolonged ustekinumab treatment in a patient with Crohn's disease and paradoxical psoriasis. PMID- 26559394 TI - Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites. AB - Pomegranate shows neuroprotective effects against Alzheimer's disease (AD) in several reported animal studies. However, whether its constituent ellagitannins and/or their physiologically relevant gut microbiota-derived metabolites, namely, urolithins (6H-dibenzo[b,d]pyran-6-one derivatives), are the responsible bioactive constituents is unknown. Therefore, from a pomegranate extract (PE), previously reported by our group to have anti-AD effects in vivo, 21 constituents, which were primarily ellagitannins, were isolated and identified (by HPLC, NMR, and HRESIMS). In silico computational studies, used to predict blood-brain barrier permeability, revealed that none of the PE constituents, but the urolithins, fulfilled criteria required for penetration. Urolithins prevented beta-amyloid fibrillation in vitro and methyl-urolithin B (3-methoxy-6H dibenzo[b,d]pyran-6-one), but not PE or its predominant ellagitannins, had a protective effect in Caenorhabditis elegans post induction of amyloid beta(1-42) induced neurotoxicity and paralysis. Therefore, urolithins are the possible brain absorbable compounds which contribute to pomegranate's anti-AD effects warranting further in vivo studies on these compounds. PMID- 26559395 TI - Design and development of controlled release floating matrix tablet of Nicorandil using hydrophilic cellulose and pH-independent acrylic polymer: in-vitro and in vivo evaluations. AB - OBJECTIVES: The purpose of the study was to develop a floating matrix tablet of Nicorandil using blends of hydrophilic cellulose and pH-independent acrylic polymer to improve the therapeutic effectiveness of the drug in cardiovascular disease. METHODS: Nicorandil tablets were prepared by direct compression and evaluated for drug-excipients compatibility, in-vitro buoyancy and in-vivo gamma scintigraphy study. The selected formulation (FT5) was also evaluated for stability study and the in-vivo absorption in rabbits to compare the pharmacokinetic parameters with the commercially available immediate release tablet of Nicorandil. RESULTS: DSC and FT-IR studies confirmed the absence of incompatibility and were found stable at refrigerator temperature (2-8 degrees C) and at 25oC/60% RH. The in-vivo gamma-scintigraphy studies revealed that the system was floated for a period of 6 -7 h in the stomach and in-vivo absorption study showed a significant difference (p < 0.05) in the pharmacokinetic parameters (AUC increased by 3 fold and MRT by 2.5 fold) as compared to the marketed formulation. CONCLUSION: In conclusion, the developed Nicorandil floating matrix tablet improved the pharmacokinetics parameters (AUC and MRT) in rabbit plasma with expected lowering in side effects potential. PMID- 26559396 TI - The strengths and limitations of animal models in assessing the effects of red blood cell storage age on clinical outcomes. PMID- 26559397 TI - The promise of extended donor antigen typing. PMID- 26559398 TI - Donor blood lead levels and transfusion safety in a vulnerable population. PMID- 26559399 TI - Transfusion medicine illustrated. The antibody identification card in action. PMID- 26559401 TI - Effect of storage-aged red blood cell transfusions on endothelial function in healthy subjects. PMID- 26559402 TI - Transfusion management of patients receiving daratumumab therapy for advanced plasma cell myeloma. PMID- 26559403 TI - Severely elevated C-reactive protein accompanied by prolonged high fever and leukocytosis in a healthy peripheral blood stem cell donor: an atypical granulocyte-colony-stimulating factor reaction? PMID- 26559404 TI - Nanoformulation and antimicrobial evaluation of newly synthesized thiouracil derivatives. AB - The present work reports the synthesis of a new series of pyridopyrimidine derivatives. The newly synthesized compounds were characterized by various analytical and spectral techniques. In addition, their antimicrobial activity was evaluated as well as modeling studies were performed to investigate their ability to recognize and bind to the biotin carboxylase (BC)-active site. The results showed a broad spectrum antibacterial and antifungal profile of the synthesized derivatives. Docking results demonstrated that all members of this class of new derivatives were able to recognize the active site of Escherichia coli BC and form different types of bonding interactions with key active site amino acid residues. Besides the compounds with promising antimicrobial activity in addition to 6-aminothiouracil, as control, were incorporated into polycaprolactone nanoparticles to improve their water solubility, permeability through physiological barriers and consequently enhanced therapeutic efficacy. The compounds-loaded nanoparticles were prepared using single emulsion-solvent evaporation technique, and their diameters were found to be in the range 136 +/- 30 to 213 +/- 28 nm. Transmission electron microscopy (TEM) showed a spherical and dense morphology of the nanoparticles. The results also showed high entrapment efficiency of the synthesized bioactive compounds in the nanoparticles (85 +/- 5% to 91 +/- 2%) with a desirable in vitro biodegradation and release profiles. PMID- 26559405 TI - Correlates of Prevalent Disability Among HIV-Infected Elderly Patients. AB - The growing elderly population of HIV-infected patients is leading to a significant epidemiological transition and HIV infection has been proposed as a premature and accelerated aging model rending the individual more susceptible to premature disability. However, the determinants of disability among this emergent population are still lacking. Therefore, the aim of this study is to determine the correlates of prevalent disability in adults >=50 years with HIV infection. A cross-sectional study of 184 HIV-infected adults receiving ambulatory care in an HIV clinic of a tertiary care, university-affiliated hospital in Mexico City was conducted. Disability for instrumental (IADL) and basic activities of daily living (ADL) was established. Sociodemographic factors, clinical variables, current CD4(+) cell count, and HIV viral load (VL) were tested as potential determinants of disability. Multivariate logistic regression analyses were used to identify the correlates of both types of disability. The mean age was 59.3 years. All participants were receiving highly active antiretroviral therapy. Of participants 17.9% had disability for IADL and 26.1% for ADL. Multivariate logistic regression analyses indicated that being older; having a lower CD4(+) cell count, and having a detectable HIV VL were independently associated with both types of disability. In addition, educational level was also independently associated with ADL disability. Age, educational level, low CD4(+) cell count, and detectable HIV VL were independently associated with disability. Whether effective and timely antiretroviral therapy will reduce the risk of disability in HIV-infected elderly patients needs to be evaluated. PMID- 26559406 TI - The Activity of Neutral alpha-Glucosidase and Selected Biochemical Parameters in the Annual Cycle of Breeding Carp (Cyprinus carpio L.). AB - The aim of the study was to demonstrate seasonal changes in the hydrolytic and transferase activity of neutral alpha-glucosidase, the level of glucose, cholesterol, triglycerides and total protein in the annual breeding cycle of the carp. The study was conducted on fish from a fish farm in Lower Silesia (Poland). Blood serum was collected from the heart in: June, September and December of two consecutive years. The results of the study show that the hydrolytic and transferase activity of neutral alpha-glucosidase, as well as the results of basic biochemical parameters are highest in summer, when the fish seek and intake food intensively. The lowest values were observed in spring, when carp have the lowest metabolism after the wintering period. PMID- 26559407 TI - Analysis of the Optimal Duration of Behavioral Observations Based on an Automated Continuous Monitoring System in Tree Swallows (Tachycineta bicolor): Is One Hour Good Enough? AB - Studies of animal behavior often rely on human observation, which introduces a number of limitations on sampling. Recent developments in automated logging of behaviors make it possible to circumvent some of these problems. Once verified for efficacy and accuracy, these automated systems can be used to determine optimal sampling regimes for behavioral studies. Here, we used a radio-frequency identification (RFID) system to quantify parental effort in a bi-parental songbird species: the tree swallow (Tachycineta bicolor). We found that the accuracy of the RFID monitoring system was similar to that of video-recorded behavioral observations for quantifying parental visits. Using RFID monitoring, we also quantified the optimum duration of sampling periods for male and female parental effort by looking at the relationship between nest visit rates estimated from sampling periods with different durations and the total visit numbers for the day. The optimum sampling duration (the shortest observation time that explained the most variation in total daily visits per unit time) was 1h for both sexes. These results show that RFID and other automated technologies can be used to quantify behavior when human observation is constrained, and the information from these monitoring technologies can be useful for evaluating the efficacy of human observation methods. PMID- 26559408 TI - A hydrodynamic view of the first-passage folding of Trp-cage miniprotein. AB - We study folding of Trp-cage miniprotein in the conditions when the native state of the protein is stable and unfolding events are improbable, which corresponds to physiological conditions. Using molecular dynamics simulations with an implicit solvent model, an ensemble of folding trajectories from unfolded (practically extended) states of the protein to the native state was generated. To get insight into the folding kinetics, the free energy surface and kinetic network projected on this surface were constructed. This, "conventional" analysis of the folding reaction was followed by a recently proposed hydrodynamic description of protein folding (Chekmarev et al. in Phys Rev Lett 100(1):018107, 2008), in which the process of the first-passage folding is viewed as a stationary flow of a folding "fluid" from the unfolded to native state. This approach is conceptually different from the previously used approaches and thus allows an alternative view of the folding dynamics and kinetics of Trp-cage, the conclusions about which are very diverse. In agreement with most previous studies, we observed two characteristic folding pathways: in one pathway (I), the collapse of the hydrophobic core precedes the formation of the [Formula: see text]-helix, and in the other pathway (II), these events occur in the reverse order. We found that although pathway II is complicated by a repeated partial protein unfolding, it contributes to the total folding flow as little as ~10%, so that the folding kinetics remain essentially single-exponential. PMID- 26559409 TI - Behavioral Disinhibition Can Foster Intentions to Healthy Lifestyle Change by Overcoming Commitment to Past Behavior. AB - To curb the trend towards obesity and unhealthy living, people may need to change their entire lifestyle to a healthier alternative, something that is frequently perceived to be problematic. The present research, using a large, representative community sample, hypothesized and found that a key factor responsible for why people do not intend to change lifestyles is a sense of commitment to past behavior. However we also found that the contribution of commitment was attenuated for individuals with a stronger tendency for behavioral disinhibition thus underscoring the "bright side" of this individual difference characteristic that traditionally has been mainly associated with impulsive and indulging behavior. Overall, the present findings add to our understanding of factors inhibiting and promoting healthy behavior change. PMID- 26559410 TI - Interactions between Canopy Structure and Herbaceous Biomass along Environmental Gradients in Moist Forest and Dry Miombo Woodland of Tanzania. AB - We have limited understanding of how tropical canopy foliage varies along environmental gradients, and how this may in turn affect forest processes and functions. Here, we analyse the relationships between canopy leaf area index (LAI) and above ground herbaceous biomass (AGBH) along environmental gradients in a moist forest and miombo woodland in Tanzania. We recorded canopy structure and herbaceous biomass in 100 permanent vegetation plots (20 m * 40 m), stratified by elevation. We quantified tree species richness, evenness, Shannon diversity and predominant height as measures of structural variability, and disturbance (tree stumps), soil nutrients and elevation as indicators of environmental variability. Moist forest and miombo woodland differed substantially with respect to nearly all variables tested. Both structural and environmental variables were found to affect LAI and AGBH, the latter being additionally dependent on LAI in moist forest but not in miombo, where other factors are limiting. Combining structural and environmental predictors yielded the most powerful models. In moist forest, they explained 76% and 25% of deviance in LAI and AGBH, respectively. In miombo woodland, they explained 82% and 45% of deviance in LAI and AGBH. In moist forest, LAI increased non-linearly with predominant height and linearly with tree richness, and decreased with soil nitrogen except under high disturbance. Miombo woodland LAI increased linearly with stem density, soil phosphorous and nitrogen, and decreased linearly with tree species evenness. AGBH in moist forest decreased with LAI at lower elevations whilst increasing slightly at higher elevations. AGBH in miombo woodland increased linearly with soil nitrogen and soil pH. Overall, moist forest plots had denser canopies and lower AGBH compared with miombo plots. Further field studies are encouraged, to disentangle the direct influence of LAI on AGBH from complex interrelationships between stand structure, environmental gradients and disturbance in African forests and woodlands. PMID- 26559411 TI - Molecular and Morphological Differentiation of Common Dolphins (Delphinus sp.) in the Southwestern Atlantic: Testing the Two Species Hypothesis in Sympatry. AB - The taxonomy of common dolphins (Delphinus sp.) has always been controversial, with over twenty described species since the original description of the type species of the genus (Delphinus delphis Linnaeus, 1758). Two species and four subspecies are currently accepted, but recent molecular data have challenged this view. In this study we investigated the molecular taxonomy of common dolphins through analyses of cytochrome b sequences of 297 individuals from most of their distribution. We included 37 novel sequences from the Southwestern Atlantic Ocean, a region where the short- and long-beaked morphotypes occur in sympatry, but which had not been well sampled before. Skulls of individuals from the Southwestern Atlantic were measured to test the validity of the rostral index as a diagnostic character and confirmed the presence of the two morphotypes in our genetic sample. Our genetic results show that all common dolphins in the Atlantic Ocean belong to a single species, Delphinus delphis. According to genetic data, the species Delphinus capensis is invalid. Long-beaked common dolphins from the Northeastern Pacific Ocean may constitute a different species. Our conclusions prompt the need for revision of currently accepted common dolphin species and subspecies and of Delphinus delphis distribution. PMID- 26559412 TI - Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. AB - BACKGROUND AND AIMS: Postoperative delirium (POD) is a common and serious surgical complication among the elderly, especially in those with amnestic mild cognitive impairment (aMCI). Dexmedetomidine (DEX) is neuroprotective for delirium. In this study, we determined the effect of intravenously administered DEX during general anesthesia on POD in elderly aMCI patients undergoing elective hip joint or knee joint or shoulder joint replacement surgery. METHODS: This was a prospective, randomized parallel-group study of aMCI (n = 80) and normal elderly patients (n = 120). Prior to surgery, all subjects underwent neuropsychological assessment and were assigned to one of four groups: the aMCI DEX group (MD group, n = 40), the aMCI normal saline group (MN group, n = 40), the control DEX group (CD group, n = 60), and the control normal saline group (CN group, n = 60). The confusion assessment method was used to screen POD on postoperative days 1, 3, and 7. RESULTS: We found patients age was positively correlated with POD incidence in the MN group (p < 0.05) but not in the CN group (p < 0.05). DEX treatment significantly decreased POD incidence in both control and aMCI groups relative to their respective placebo groups (all p < 0.05). The fraction of patients whose normal cognitive function was not restored by day 7 after surgery was significantly higher in the MN group than the MD and CN groups (all p < 0.05). CONCLUSIONS: These findings suggested that DEX treatment during surgery significantly reduced POD incidence in both normal and aMCI elderly patients, suggesting that it may be an effective option for the prevention of POD. PMID- 26559413 TI - Assessment of fatigability of older women during sit-to-stand performance. AB - BACKGROUND: Fatigability of older adults is relevant with regard to physical performance, falls and physical activity. Objective and inexpensive assessment tools for testing fatigability in the persons' home environment are not available. AIMS: The aim of this study was to develop a protocol to objectively measure fatigability during repeated sit-to-stand performance in older persons. METHODS: Decrease of maximum velocity of performance during repeated sit-to-stand transfers and the number of repetition when achieving a 10, 15, and 20 % fatigue threshold were measured in 49 community-dwelling older women using a linear encoder. RESULTS: Mean maximum velocity of the sit-to-stand performance was 1.12 m/s (SD 0.17 m/s) with an estimated change of velocity per repetition of -0.0037 m/s (95 % CI -0.0039 to -0.0035) during the test. The mean number of repetitions representing 10, 15, and 20 % fatigue threshold was 8.1, 13.8, and 21, respectively. DISCUSSION: This simple test protocol provides objective information about the decrease of performance of a daily task in older adults. CONCLUSION: Fatigability of the sit-to-stand performance can be measured objectively by measuring the decrease of maximum velocity of consecutive repetitions and the repetition number achieving a 20 % fatigue threshold. PMID- 26559414 TI - Is it always Alzheimer's? Let's talk to our patients about "cardiocerebrovascular" prevention. AB - Unlike Alzheimer's, vascular dementia can, in part, be prevented. The preventive approach foresees treatment for high blood pressure, atrial fibrillation, diabetes, high cholesterol, low HDL cholesterol, sedentary lifestyle, smoking, alcohol abuse, obesity, and sleep apnea. Moreover, also a well-balanced diet and physical activity are cornerstones of prevention, with beneficial effects on the brain and cognition. PMID- 26559415 TI - A comparison of the femur heads histomorphometrically regarding trabecular bone properties in the patients with osteoporosis and osteoarthritis. AB - The purpose was to compare the bone samples histomorphometrically regarding trabecular bone properties in the patients with osteoarthritis (OA) and osteoporosis (OP). Femoral head specimens were obtained from 18 patients with OA and 17 patients with femoral neck fracture due to OP during hip arthroplasty. Histomorphometric analyses were performed by soft ware program (Carl Zeiss) to measure trabecular area (Tb.a, mm(3)), trabecular thickness (Tb.th, um) and trabecular separation (Tb.s, um). In the results, Tb.a and Tb.th values were significantly lower (p < 0.05), Tb.s was higher in the patients with OP (p < 0.05). Bone metabolism parameters were different between the groups (p < 0.05). All histomorphometric parameters were highly correlated with the BMDs (p < 0.01). This study showed inverse relation between OA and OP regarding trabecular bone properties, BMD and bone turnover metabolism markers. The strong relations between results suggest that either BMDs or bone turnover markers can be used for prescience of the fractures. PMID- 26559416 TI - Management of hepatitis B during pregnancy. AB - INTRODUCTION: Women of childbearing age or who are pregnant and have hepatitis B infection require specialized management both during and after pregnancy. Effective maternal screening along with judicious use of available antivirals and immunoprophylaxis greatly reduces the perinatal transmission of hepatitis B virus (HBV) and dramatically declines the incidence and prevalence of chronic hepatitis B and its sequelae. AREAS COVERED: A systematic literature search was done using Embase, Medline and Cochrane library from January 1990 to July 2015 and appropriate articles selected for this review. This review highlights the timing of therapy, choice of antiviral agent along with passive and active immunoprophylaxis for infants. Issues regarding breastfeeding in HBV-infected women and who are on antiviral therapy are addressed. EXPERT OPINION: All decisions about starting, continuing or stopping antiviral therapy must consider maternal and fetal risks. Antiviral therapy during the third trimester of pregnancy in women with active disease reduces the risk of perinatal transmission. Safety data in pregnancy are mostly available for lamivudine and tenofovir. However, recent studies have also advocated use of telbivudine in such patients. Detailed discussion with the patient regarding the risks and benefits of therapy is very important. Prophylaxis remains the best method of prevention of perinatal transmission. PMID- 26559417 TI - Public Attitudes to Housing Systems for Pregnant Pigs. AB - Understanding concerns about the welfare of farm animals is important for the development of socially sustainable production practices. This study used an online survey to test how views on group versus stall housing for pregnant sows varied when Canadian and US participants were provided information about these systems, including access to scientific papers, YouTube videos, Google images, and a frequently-asked-questions page (S1 Appendix). Initial responses and changes in responses after accessing the information were analyzed from Likert scores of 242 participants and from their written comments. Participants were less willing to accept the use of gestation stalls after viewing information on sow housing. For example, initially 30.4% of respondents indicated that they supported the use of gestation stalls; this declined to 17.8% after participants were provided additional information. Qualitative analysis of comments showed that supporters of gestation stalls expressed concern about the spread of disease and aggression between animals in less confined systems, whereas supporters of group housing placed more emphasis on the sow's ability to interact socially and perform natural behaviors. These results point to public opposition to the use of gestation stalls, and indicate that the more that the public learns about gestation stalls the less willing they will be to accept their use. PMID- 26559419 TI - On-site hemostatic suturing for placenta previa: concerns and clarifications. PMID- 26559418 TI - Application of Pseudomonas fluorescens to Blackberry under Field Conditions Improves Fruit Quality by Modifying Flavonoid Metabolism. AB - Application of a plant growth promoting rhizobacterium (PGPR), Pseudomonas fluorescens N21.4, to roots of blackberries (Rubus sp.) is part of an optimised cultivation practice to improve yields and quality of fruit throughout the year in this important fruit crop. Blackberries are especially rich in flavonoids and therefore offer potential benefits for human health in prevention or amelioration of chronic diseases. However, the phenylpropanoid pathway and its regulation during ripening have not been studied in detail, in this species. PGPR may trigger flavonoid biosynthesis as part of an induced systemic response (ISR) given the important role of this pathway in plant defence, to cause increased levels of flavonoids in the fruit. We have identified structural genes encoding enzymes of the phenylpropanoid and flavonoid biosynthetic pathways catalysing the conversion of phenylalanine to the final products including flavonols, anthocyanins and catechins from blackberry, and regulatory genes likely involved in controlling the activity of pathway branches. We have also measured the major flavonols, anthocyanins and catechins at three stages during ripening. Our results demonstrate the coordinated expression of flavonoid biosynthetic genes with the accumulation of anthocyanins, catechins, and flavonols in developing fruits of blackberry. Elicitation of blackberry plants by treatment of roots with P.fluorescens N21.4, caused increased expression of some flavonoid biosynthetic genes and an accompanying increase in the concentration of selected flavonoids in fruits. Our data demonstrate the physiological mechanisms involved in the improvement of fruit quality by PGPR under field conditions, and highlight some of the genetic targets of elicitation by beneficial bacteria. PMID- 26559420 TI - Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta hCG on fetal growth restriction: results of a prospective study. AB - PURPOSE: Low levels of plasmatic pregnancy-associated plasma protein-A (PAPP-A) and high levels of free-beta human chorionic gonadotropin (beta-hCG) could influence the outcome of pregnancy. The objective of this study is to assess the correlation between PAPP-A and free beta-hCG and birth weight. MATERIALS AND METHODS: Prospective follow-up study performed on 3332 patients in the first trimester of pregnancy who were subjected to a screening test focused on evaluation of fetal aneuploidy (SCA-TEST). The values of PAPP-A and free beta-hCG were both analyzed as raw values and subsequently converted to a multiple of the median (MoM). Statistical analysis was performed using SPSS version 17.0.1 (SPSS Inc., Chicago, USA). RESULTS: The incidence of "small for gestational age" in patients with PAPP-A MoM <1st and <5th 0/00 was statistically significant (12 and 9.8 %; p < 0.0001). Also statistically significant data have been highlighted about free beta MoM > 95th 0/00 (7 %; p = 0.03). The values of PAPP-A MoM > 99th 0/00 are significantly correlated with an increased risk of "large for gestational age" (16.7 %; p < 0.0001). CONCLUSION: Our study demonstrates that specific values of PAPP-A and free beta-hCG could identify the risk of low or high birth weight since the first trimester of pregnancy. PMID- 26559421 TI - Q fever and pregnancy: experience from the Limoges Regional University Hospital. AB - INTRODUCTION: Q fever is an ubiquitous zoonosis caused by Coxiella burnetii. Its tropism for the uterus is a potential source of obstetric complications. MATERIALS AND METHODS: We describe the obstetric consequences of Q fever diagnosed during pregnancy from a series of cases. When an antenatal diagnosis was made, antibiotic therapy with roxithromycin (Rulid((r))) was started until delivery. RESULTS: Between 2007 and 2012, 30 patients were treated for Q fever diagnosed during pregnancy, i.e. 1.9 cases per 1000 people. The most common reasons for performing serology was intrauterine growth retardation, preterm labor and oligoamnios. Q fever was diagnosed as acute and chronic in 26 and 4 cases, respectively. Progression to chronic disease occurred in 8 % of acute forms of the diseases. The prevalence of obstetric complications was 66 %, including 10 % foetal deaths, 31 % preterm delivery and 27 % low birthweight <10th percentile. The obstetric complication rate amongst the 22 patients treated with ante partum macrolides was 60, 30 % of which involved prematurity and 33 % involved low growth. No cases of foetal death were found on treatment and no congenital malformation and placental or neonatal injury was found. No case of disease reactivation was diagnosed in the eight patients who became pregnant again. CONCLUSION: Q fever during pregnancy is responsible for severe obstetric complications. It must be diagnosed early and its clinical forms known in order to start appropriate antibiotic therapy. PMID- 26559422 TI - Recurrent implantation failure in IVF: features of cycles that eventually ended in conception. AB - PURPOSE: To evaluate the characteristics of patients and IVF cycles with recurrent implantation failure who eventually succeeded to conceive compared to those who failed to do so. METHODS: In a retrospective study, we explored our database for patients younger than 35 years old who underwent at least three unsuccessful fresh IVF cycles. The following parameters were analyzed: cause of infertility, FSH level, stimulation cycle characteristics, fertilization rate, the type of luteal support, and cycle outcome. Uterine cavity assessment was also included. The relationship between endometrial scratching and the outcome of the following IVF cycle was assessed for the subsequent pregnancy rate. RESULTS: The study included 184 patients who underwent 854 IVF cycles. There were no statistically significant differences between patients who eventually conceived and those who did not in terms of ovarian reserve and response to gonadotropin treatment. IVF cycles that eventually ended with conception were characterized by shorter stimulation (10.87 +/- 2.17 versus 11.34 +/- 2.33 days, p < 0.05), higher estrogen level on the day of hCG administration (1661 +/- 667 versus 1472 +/- 633 pg/ml, p = 0.009), more fertilized oocytes via ICSI (5.04 +/- 4.29 versus 3.85 +/ 3.45, p = 0.002), and more embryos available for transfer (5.98 +/- 3.89 versus 5.12 +/- 3.31, p = 0.002). Combined estrogen and progesterone luteal support combined with endometrial scratching prior to the subsequent IVF cycle has been positively related to increased pregnancy rates. CONCLUSIONS: Young patients with RIF having a normal ovarian reserve and satisfactory ovarian response to superovulation should be encouraged to pursue IVF, even though the probability to conceive is relatively low compared to the general IVF population. PMID- 26559423 TI - Balloon kyphoplasty of T8 in an osteoporotic fracture. PMID- 26559424 TI - Extension type fracture of the ankylotic thoracic spine with gross displacement causing esophageal rupture. AB - PURPOSE: This study aimed at discussing the relevance of the type B3 fracture of the new AOSpine classification. METHODS: Hyperextension fractures of the spine are rare in the general population, but common in the ankylotic spine. We present a case of a severe spinal fracture with concomitant esophageal rupture, which was diagnosed early and could be treated during the initial trauma care. RESULTS: The spinal column was stabilized using a percutaneous technique after which the perforated esophagus was sutured through a thoracotomy. The spinal injury was classified a type B3 fracture using the new AOSpine classification. CONCLUSION: The B3 typification raised a lot of discussion during the development of the new classification system and may be controversial. This case, however, nicely illustrates the relevance of an intact posterior hinge as compared to C-type injuries where complete dissociation is present with inherent spinal cord damage. PMID- 26559425 TI - Nondestructive evaluation of photosynthesis by delayed luminescence in Arabidopsis in Petri dishes. AB - Nondestructive evaluation of photosynthesis is a valuable tool in the field and laboratory. Delayed luminescence (DL) can reflect charge recombination through the backflow of electrons. However, DL detection has not yet been adapted for whole plants in Petri dishes. To compensate for differences in DL decay between sibling Arabidopsis plants grown under the same conditions, we developed a time sequential double measurement method. Using this method, we examined the influence of photosynthetic electron flow inhibitors, and differences in the DL decay curves were categorized by considering the initial and late phases of the decay curves, as well as their intermediate slopes. The appearance of concavity and convexity in DL curves in Arabidopsis was different from unicellular algae, suggesting complexity in the photosynthetic machinery of higher plants. This detection method should be invaluable for evaluating photosynthetic defects in higher plants under sterile conditions without interrupting plant culture. PMID- 26559426 TI - Prevalence of Obstructive Sleep Apnoea Among Patients Admitted for Bariatric Surgery. A Prospective Multicentre Trial. AB - BACKGROUND: Obesity has become one of the greatest public health concerns worldwide and is known to be the most important risk factor for obstructive sleep apnoea (OSA). Prevalence of OSA has increased over the last two decades, but it is estimated that the majority of cases still remain undiagnosed. The aim of this study was to investigate the prevalence of OSA in Finnish bariatric surgery candidates. METHODS: In this prospective multicentre study, standard overnight cardiorespiratory recording was conducted in 197 consecutive patients from three different hospitals. A sleep questionnaire was also administered. Anthropometric and demographic measurements included age, weight, body mass index (BMI) and waist and neck circumference. RESULTS: Altogether, 71 % of the patients were diagnosed with OSA. The prevalence was higher in males (90 %) than in females (60 %) (p < 0.001). In OSA patients' group, the mean neck and waist circumference was larger (p < 0.001) and the body weight higher (p < 0.01) than in non-OSA group. When separating patients by gender, a significant difference remained only concerning neck circumference in female patients. CONCLUSIONS: OSA is very common among bariatric surgery patients, especially in men. Considering this and the increased long-term morbidity and mortality generally related to OSA, a routine screening for OSA seems indicated in bariatric patients, particularly men. PMID- 26559427 TI - Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges. AB - The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class effect. In lay terms "cancers follow bleeding", which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail. PMID- 26559428 TI - The use of transthoracic echocardiography for the assessment of left ventricular systolic and diastolic function in patients with suspected or ascertained chronic heart failure. AB - Several indices are available to assess left ventricular (LV) function. Although ejection fraction (EF) is widely used, it has many limitations. An assessment of LV longitudinal function should be therefore provided as it precedes the impairment of EF. In this context, speckle tracking derived global longitudinal strain is the gold standard but S' velocity of mitral annulus (by pulsed tissue Doppler) and mitral annular plane systolic excursion (by M-mode) represent more than simple surrogates. LV diastolic assessment should be oriented not to the simple classification of transmitral patterns (E/A ratio and E velocity deceleration time) but to non-invasive estimation of LV filling pressures. This can be mainly obtained from E/e' ratio, with additional calculation of other measurements such as pulmonary flow atrial reverse velocity, systolic pulmonary arterial pressure and left atrial volume index. This comprehensive assessment could also be useful to differentiate heart failure with reduced and preserved EF in particular. PMID- 26559429 TI - Antigen Detection in the Diagnosis of Histoplasmosis: A Meta-analysis of Diagnostic Performance. AB - We performed a meta-analysis of diagnostic data to evaluate the performance of Histoplasma antigen detection tests for diagnosing histoplasmosis. We included all studies involving human subjects that assessed the performance of any antigen detection test for histoplasmosis in urine or serum by carrying out an exhaustive and reproducible search of the literature between 1980 and 2014 from four databases. Quality of the articles was assessed, and meta-analysis was performed under the random effects model, calculating sensitivity, specificity, likelihood and odds ratios, and ROC curve using Meta-DiSc(es). Nine out of a total of 23 studies met strict quality criteria and were therefore included. The overall sensitivity for antigen detection in serum and urine was 81% (95% CI 78-83%), while specificity was 99% (95% CI 98-99%). Sensitivity for antigenuria and antigenemia was 79% (95% CI 76-82%) and 82% (95% CI 79-85%), respectively; specificity values were 99% (95% CI 98-100%) in urine and 97% (95% CI 96-98%) in serum. The positive and negative likelihood ratios were 49.5 (95% CI 20.7-118.7) and 0.19 (95% CI 0.14-0.26), respectively, while the diagnostic OR was 362 (95% CI 121.2-1080.3) and area under the curve was 0.99. In conclusion, the performance of Histoplasma antigen detection assay of urine was not significantly different from that of blood, indicating that antigenuria and antigenemia have equal diagnostic value in histoplasmosis. PMID- 26559430 TI - Efavirenz-based antiretroviral therapy versus nevirapine-including regimens for prevention of mother-to-child transmission of HIV option B plus in resource limited settings: is there anything missing? AB - In 2013, an estimated 1.5 million HIV-positive pregnant women gave birth, with 240,000 children worldwide acquiring HIV. More than 90% of new pediatric infections occurred in Sub-Saharan Africa. The latest WHO guidelines recommended efavirenz (EFV)-based antiretroviral therapy as the first-line regimen for prevention of mother-to-child transmission of HIV (PMTCT). On the other hand, some data suggest that nevirapine (NVP), a well-known antiretroviral, could still play a relevant role in PMTCT, especially in resource-limited settings (RLSs) where the fertility rate is dramatically high compared to developed countries. Given the lack of an unanimous consensus and definitive opinions, this paper goes through the reasons for WHO decisions and aims at refreshing the debate about NVP and EFV pros and cons for PMTCT in RLSs. PMID- 26559431 TI - 7-formyl-10-methylisoellipticine, a novel ellipticine derivative, induces mitochondrial reactive oxygen species (ROS) and shows anti-leukaemic activity in mice. AB - Acute myeloid leukaemia (AML) is the most common type of leukaemia in adults and is associated with high relapse rates. Current treatment options have made significant progress but the 5 year survival for AML remains low and therefore, there is an urgent need to develop novel therapeutics. Ellipticines, a class of cancer chemotherapeutic agents, have had limited success clinically due to low solubility and toxic side effects. Isoellipticines, novel isomers of ellipticine, have been designed to overcome these limitations. One particular isoellipticine, 7-formyl-10-methylisoellipticine, has previously showed strong ability to inhibit the growth of leukaemia cell lines. In this study the anti-leukaemia effect of this compound was investigated in detail on an AML cell line, MV4-11. Over a period of 24 h 7-formyl-10-methyl isoellipticine at a concentration of 5 MUM can kill up to 40 % of MV4-11 cells. Our research suggests that the cytotoxicity of 7 formyl-10-methylisoellipticine is partially mediated by an induction of mitochondrial reactive oxygen species (ROS). Furthermore, 7-formyl-10 methylisoellipticine demonstrated promising anti-tumour activity in an AML xenograft mouse model without causing toxicity, implying the potential of isoellipticines as novel chemotherapeutic agents in the treatment of leukaemia. PMID- 26559432 TI - Oral Absorption Promoters: Opportunities, Issues, and Challenges. AB - Transport of a drug across the biological membrane of the gastrointestinal tract has turned out to be a critical barrier against the success of any oral drug delivery technology. The unique advantages of the oral route, along with need for an oral substitute of invasive parenteral formulations and the reduction of intersubject variability in plasma profiles, has been an incentive for the use of excipients with absorption-enhancing properties to boost the bioavailability of poorly absorbed drugs. The development of such excipients is not a simple task, so understanding enhancement mechanisms in relation to physiology can facilitate the identification of structure-function relationships as well as the development of newer agents for customary applications. The literature is replete with reports of absorption promoters, the selection of which is influenced by the mechanisms, safety, pharmacological inertness, rapidity of action, reversibility of induced membrane alterations and excipient compatibility. Despite promising results in preliminary screenings, the development process is hindered by low reproducible efficacy and pharmacologically driven safety issues. In this review, we elaborate on the importance of permeation enhancers in oral drug delivery, their current status, and issues at the forefront of the development of formulations using absorption promoter technologies. PMID- 26559433 TI - Nanotechnology-Based Photodynamic Therapy: Concepts, Advances, and Perspectives. AB - Photodynamic therapy (PDT) is a photoactive process that uses the combination of photosensitizers (PSs) and specific wavelengths of light for the treatment of solid tumors and other diseases. PDT received increased attention after regulatory approval of several photosensitizing drugs and light applicators worldwide. With the advent of newer PSs, the role of PDT in the treatment of cancer and other diseases has been revolutionized. In addition, various targeting strategies developed for site-specific delivery of PSs will be helpful for avoiding phototoxicity to normal tissues. Receptor-mediated targeted PDT approaches using nanocarriers offer the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. At present, clinical application of PDT is well established in medicine and surgery. Successfully used in dermatology, urology, gastroenterology, and neurosurgery, PDT has also seen much progress in basic sciences and clinical photodynamics in recent years. Currently, the use of PDT is just beginning, and more research must be performed to prove its therapeutic efficacy. However, nontoxic compounds involved in PDT provide a certain hope that it will evolve to be an effective mechanism for combating chronic diseases. PMID- 26559434 TI - Myriad Molecules to Overcome Efflux Drug Transporters and Drug-Metabolizing Enzymes: A Journey from Synthetic to Natural. AB - A vast range of prescribed drugs suffers from low and variable bioavailability mainly because of metabolism and permeation complications. This issue of bioavailability is a key problem that has been ongoing for many years. Various tactics have been introduced that have been quite beneficial for improving the bioavailability of poorly bioavailable drugs. Some of these tactics are targeted on cytochrome-P450 (CYP) enzymes and the permeability-glycoprotein (P-gp) efflux pump. Strategies include small-molecule inhibitors, novel drug-delivery systems, pharmaceutical synthetic excipients, and natural bioenhancers. This review discusses the role of synthetic excipients and natural bioenhancers in potentiating the activity of poorly bioavailable drugs, including their pharmacological background and their future applicability to health care. The molecules of synthetic origin such as Gelucire and those of natural origin such as quercetin and silibinin can provide noteworthy benefits to patients and the health care system by helping to reduce dosing and drug side effects. PMID- 26559435 TI - A Whole-Body Physiologically Based Pharmacokinetic Model of Gefitinib in Mice and Scale-Up to Humans. AB - Gefitinib (Iressa) is a selective and potent EGFR tyrosine kinase inhibitor. It received an accelerated FDA approval in 2003 for the treatment of patients with nonsmall cell lung cancer (NSCLC) and represents the first-line therapy for NSCLC with EGFR mutations. In the work presented herein, the disposition of gefitinib was investigated extensively in mouse in both plasma and 11 organs (liver, heart, lung, spleen, gut, brain, skin, fat, eye, kidney, and muscle) after a single IV dose of 20 mg/kg. Gefitinib demonstrated extensive distribution in most tissues, except for the brain, and tissue to plasma partition coefficients (K pt) ranged from 0.71 (brain) to 40.5 (liver). A comprehensive whole-body physiologically based pharmacokinetic (PBPK) model of gefitinib in mice was developed, which adequately captured gefitinib concentration-time profiles in plasma and various tissues. Predicted plasma and tissue AUC values agreed well with the values calculated using the noncompartmental analysis (<25% difference). The PBPK model was further extrapolated to humans after taking into account the interspecies differences in physiological parameters. The simulated concentrations in human plasma were in line with the observed concentrations in healthy volunteers and patients with solid malignant tumors after both IV infusion and oral administration. Considering the extensive tissue distribution of gefitinib, plasma concentration may not be an ideal surrogate marker for gefitinib exposure at the target site or organ of toxicity (such as the skin). Since our whole-body PBPK model can predict gefitinib concentrations not only in plasma but also in various organs, our model may have clinical applications in efficacy and safety assessment of gefitinib. PMID- 26559436 TI - Antiviral treatment for Bell's palsy (idiopathic facial paralysis). AB - BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. This review was first published in 2001 and revised several times, most recently in 2009. This version replaces an update of the review in Issue 7 of the Cochrane Library subsequently withdrawn because of an ongoing investigation into the reliability of data from an included study. OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS: On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials or quasi randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. DATA COLLECTION AND ANALYSIS: Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. MAIN RESULTS: Ten trials, including 2280 participants, met the inclusion criteria and are included in the final analysis. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found a significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.39 to 0.97, n = 1315). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used, compared to corticosteroids alone (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants receiving corticosteroids alone was significantly better than for those receiving antivirals alone (RR 2.82, 95% CI 1.09 to 7.32, n = 768). The treatment effect of placebo was significantly lower than that of antivirals plus corticosteroids (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone produced no benefit compared with placebo (RR 1.10, 95% CI 0.87 to 1.40, n = 658). Motor synkinesis or crocodile tearsIn two trials comparing antivirals and corticosteroids with corticosteroids and placebo that assessed this outcome, we found a significant difference in long-term sequelae in favour of antivirals plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87, n = 469). Two trials comparing antivirals alone with corticosteroids alone investigating this outcome showed fewer sequelae with corticosteroids (RR 1.52, 95% CI 1.08 to 2.12, n = 472). We found no data on long term sequelae for other comparisons. Adverse events Adverse event data were available in three studies giving comparison data on 1528 participants. None of the four comparisons (antivirals plus corticosteroids versus corticosteroids plus placebo or no treatment; antivirals versus corticosteroids; antivirals plus corticosteroids versus placebo; antivirals versus placebo) showed significant differences in adverse events between treatment and control arms. We could find no correlation with specific treatment within these results. AUTHORS' CONCLUSIONS: Low-quality evidence from randomised controlled trials showed a benefit from the combination of antivirals with corticosteroids compared to corticosteroids alone for the treatment of Bell's palsy of various degrees of severity. Low-quality evidence showed a benefit of combination therapy compared with corticosteroids alone in severe Bell's palsy. Corticosteroids alone were more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no benefit from antivirals alone over placebo.Moderate-quality evidence indicated that the combination of antivirals and corticosteroids reduced sequelae of Bell's palsy compared with corticosteroids alone.We found no significant increase in adverse events from the use of antivirals compared with either placebo or corticosteroids, based on low quality evidence. PMID- 26559438 TI - Radiation dose efficiency of dual-energy CT benchmarked against single-source, kilovoltage-optimized scans. AB - OBJECTIVE: This study evaluated the radiation dose and image quality implications of dual-energy CT (DECT) use, compared with kilovoltage-optimized single source/single-energy CT (SECT) on a dual-source Siemens Somatom((r)) Definition Flash CT scanner (Siemens Healthcare, Forcheim, Germany). METHODS: With equalized radiation dose (volumetric CT dose index), image noise (standard deviation of CT number) and signal-difference-to-noise ratio (SDNR) were measured and compared across three techniques: 100, 120 and 100/140 kVp (dual energy). Noise in a 30-cm diameter water phantom and SDNR within unenhanced soft-tissue regions of a small adult (50 kg/165 cm) anthropomorphic phantom were utilized for the assessment. RESULTS: Water phantom image noise decreased with DECT compared with the lower noise SECT setting of 120 kVp (p = 0.046). A decrease in SDNR within the anthropomorphic phantom was demonstrated at 120 kVp compared with the SECT kilovoltage-optimized setting of 100 kVp (p = 0.001). A further decrease in SDNR was observed for the DECT technique when compared with 120 kVp (p = 0.01). CONCLUSION: On the Siemens Somatom Definition Flash system (Siemens Healthcare), and for equalized radiation dose conditions, image quality expressed as SDNR of unenhanced soft tissue may be compromised for DECT when compared with kilovoltage optimized SECT, particularly for smaller patients. ADVANCES IN KNOWLEDGE: DECT on a dual-source CT scanner may require a radiation dose increase to maintain unenhanced soft-tissue contrast detectability, particularly for smaller patients. PMID- 26559437 TI - Toxicity assessment and bioaccumulation in zebrafish embryos exposed to carbon nanotubes suspended in Pluronic(r) F-108. AB - Carbon nanotubes (CNTs) are often suspended in Pluronic(r) surfactants by sonication, which may confound toxicity studies because sonication of surfactants can create degradation products that are toxic to mammalian cells. Here, we present a toxicity assessment of Pluronic(r) F-108 with and without suspended CNTs using embryonic zebrafish as an in vivo model. Pluronic(r) sonolytic degradation products were toxic to zebrafish embryos just as they were to mammalian cells. When the toxic Pluronic(r) fragments were removed, there was little effect of pristine multi-walled CNTs (pMWNTs), carboxylated MWNTs (cMWNTs) or pristine single-walled carbon nanotubes (pSWNTs) on embryo viability and development, even at high concentrations. A gel electrophoretic method coupled with Raman imaging was developed to measure the bioaccumulation of CNTs by zebrafish embryos, and dose-dependent uptake of CNTs was observed. These data indicate that embryos accumulate pMWNTs, cMWNTs and pSWNTs yet there is very little embryo toxicity. PMID- 26559439 TI - Nodal metastasis and elective nodal level treatment in sinonasal small-cell and sinonasal undifferentiated carcinoma: a surveillance, epidemiology and end results analysis. AB - OBJECTIVE: Risk of nodal involvement in patients with sinonasal small-cell carcinoma and sinonasal undifferentiated carcinoma (SNUC) has not been well defined because of their rarity. We describe a population-based assessment of specific nodal level involvement in this group of rare neuroectodermal tumours. METHODS: The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2011 identified patients with SNUC and sinonasal small-cell carcinoma. Overall neck involvement and individual nodal level involvement at presentation were assessed, and comparison was made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. RESULTS: Of 141 patients, 31 (22%) had gross nodal involvement at presentation (range 14-33% by site and histology). Non-nasal, non-ethmoid site with SNUC histology has the highest rates of initial nodal involvement, whereas higher stage and size do not predict for higher nodal involvement rates. Bilateral Levels 2-3 for all sinonasal small cell; Levels 2-3 for nasal or ethmoid SNUC; and bilateral Levels 1-3 in non-nasal/non-ethmoid SNUC have the highest rates of involvement compared with a clinical reference standard. CONCLUSION: We found high rates of initial nodal involvement in all SNUC and sinonasal small-cell carcinoma. We found higher initial involvement of Levels 2 and 3 and in certain cases to the Level 1 nodal levels, hypothesizing benefit for elective treatment to those levels. ADVANCES IN KNOWLEDGE: With small single-institution series reporting conflicting nodal involvement rates, our data support high rates of nodal presentation at diagnosis, hypothesizing benefit for elective nodal treatment in this cohort. PMID- 26559440 TI - Effect of total lung capacity and gender on CT densitometry indexes. AB - OBJECTIVE: Testing the hypothesis that CT densitometry indexes could be influenced by total lung capacity (TLC), gender and height in normal individuals. METHODS: In this ethics committee-approved prospective study, 100 healthy non smoking volunteers who provided written informed consent were included. From a helical scan of the chest, the relative area (RA) of the lung with attenuation coefficients lower than -960 HU and the 1st and 15th percentiles of the distribution of attenuation coefficients were calculated. Regression lines were drawn between each CT index and volunteers' height and total TLC at CT. RESULTS: In males, there was no statistically significant correlation between any CT index and height. In females, there was a statistically significant correlation between the RA of the lung with attenuation coefficients lower than -960 HU and the 1st percentile and height but not with the 15th percentile. For both genders, there were significant correlations between all CT indexes and TLC. The relationships between CT indexes and TLC were different in males and females. CONCLUSION: CT indexes are correlated with TLC and height but more closely with TLC than with height, and differently in males and females. ADVANCES IN KNOWLEDGE: CT indexes are influenced by TLC, gender and height in normal individuals and are more closely correlated with TLC than with height. The relationships between CT indexes and TLC or height are different in males and females. CT indexes used to quantify emphysema should thus be adjusted according to TLC and gender. PMID- 26559441 TI - Accuracy of GE digital breast tomosynthesis vs supplementary mammographic views for diagnosis of screen-detected soft-tissue breast lesions. AB - OBJECTIVE: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment of soft-tissue mammographic abnormalities. METHODS: Women recalled for further assessment of soft-tissue abnormalities were recruited and received standard supplementary views (typically spot compression views) and two-view GE DBT. The added value of DBT in the assessment process was determined by analysing data collected prospectively by radiologists working up the cases. Following anonymization of cases, there was also a retrospective multireader review. The readers first read bilateral standard two-view digital mammography (DM) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale. The same readers then read bilateral standard two-view DM together with two-view DBT. Pathology data were obtained. Differences were assessed using receiver operating characteristic analysis. RESULTS: The study population was 342 lesions in 322 patients. The final diagnosis was malignant in 113 cases (33%) and benign/normal in 229 cases (67%). In the prospective analysis, the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and standard mammographic supplementary views-the area under the curve (AUC) was 0.946 and 0.922, respectively, which did not reach statistical significance. Similar results were obtained for the retrospective review-AUC was 0.900 (DBT) and 0.873 (supplementary views), which did not reach statistical significance. CONCLUSION: The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of standard supplementary mammographic views. ADVANCES IN KNOWLEDGE: The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment. This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities. PMID- 26559442 TI - An unusual cause of cardiothyreosis. AB - Severe hyperthyroidism can cause cardiac complications, such as severe rhythm disturbances, heart failure and angina. Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from benign hydatidiform mole to malignant form. Clinical hyperthyroidism may occur in GTD, as human chorionic gonadotropin (hCG) secreted by molar tissue is structurally similar to thyroid stimulating hormone. Cardiothyreosis in this context is exceptional. We report the case of a nulligravida 42-year-old woman without thyroid or cardiac history who presented to the emergency department for dyspnoea. Examinations revealed an acute pulmonary oedema and sinus tachycardia. Serum hCG concentration was abnormally high (762 878 UI/l, N < 5). CT scan showed a voluminous uterine mass and eliminated pulmonary embolism. Cardiac output was increased in echocardiography. Complementary blood tests showed a peripheral hyperthyroidism. GTD was evoked in the context of uterine mass and high hCG concentration, which was responsible for inducing clinical hyperthyroidism and cardiothyreosis. A total hysterectomy was performed and histopathological examinations concluded to a non-invasive complete hydatidiform mole (begnin form). hCG fell to normal within 12 weeks, cardiac and thyroid functions normalized after mole evacuation. PMID- 26559443 TI - Anterior cruciate ligament injuries in elite and high school rugby players: a 11 year review. AB - OBJECTIVES: Over a 11-year period, we investigated the incidence of anterior cruciate ligament (ACL) injuries and the clinical outcomes after ACL reconstruction with hamstring autografts in two homogenous cohorts of rugby players. METHODS: Two teams, including those in elite (94 players) and high school (290 players) clubs, were followed. RESULTS: Isolated ACL injuries occurred in 28 players (12 elite, 16 high school). The incidence during match play was 1.26 per 1000 player-hours (95% confidence interval [95% CI]: 0.48-2.05) among elite players and 0.97 per 1000 player-hours (95% CI: 0.30-1.64) among high school players. After ACL reconstruction, 26 players (12 elite, 14 high school) were successfully contacted for follow-up at a mean of 71.9 months. None (0%) of the elite and 4 (29%) of the high school players experienced graft ruptures. Seven (58%) elite and 10 (91%) high school players were fearful of reinjury; the mean time to overcome this fear was 6.1 +/- 4.9 months among elite players and 17.5 +/- 26.0 months among high school players. CONCLUSION: In conclusion, young rugby players experienced inferior outcomes after ACL reconstruction with hamstring autografts compared with their older counterparts. PMID- 26559444 TI - Local sustainability and scaling up for user fee exemptions: medical NGOs vis-a vis health systems. AB - Free healthcare obviously works when a partner from abroad supplies a health centre or a health district with medicines and funding on a regular basis, provides medical, administrative and managerial training, and gives incentive bonuses and daily subsistence allowances to staff. The experiments by three international NGO in Burkina Faso, Mali and Niger have all been success stories. But withdrawing NGO support means that health centres that have enjoyed a time of plenty under NGO management will return to the fold of health centres run by the state in its present condition and the health system in its present condition, with the everyday consequences of late reimbursements and stock shortages. The local support given by international NGOs has more often than not an effect of triggering an addiction to aid instead of inducing local sustainability without infusion. In the same way, scaling up to the entire country a local pilot experiment conducted under an NGO involves its insertion into a national bureaucratic machine with its multiple levels, all of which are potential bottlenecks. Only experiments carried out under the "ordinary" management of the state are capable of laying bare the problems associated with this process. Without reformers 'on the inside' (within the health system itself and among health workers), no real reform of the health system induced by reformers 'from the outside' can succeed. PMID- 26559445 TI - Theoretical study of the coordination behavior of formate and formamidoximate with dioxovanadium(V) cation: implications for selectivity towards uranyl. AB - Poly(acrylamidoxime)-based fibers bearing random mixtures of carboxylate and amidoxime groups are the most widely utilized materials for extracting uranium from seawater. However, the competition between uranyl (UO2(2+)) and vanadium ions poses a significant challenge to the industrial mining of uranium from seawater using the current generation of adsorbents. To design more selective adsorbents, a detailed understanding of how major competing ions interact with carboxylate and amidoxime ligands is required. In this work, we employ density functional theory (DFT) and wave-function methods to investigate potential binding motifs of the dioxovanadium ion, VO2(+), with water, formate, and formamidoximate ligands. Employing higher level of theory calculations (CCSD(T)) resolve the existing controversy between the experimental results and previous DFT calculations for the structure of the hydrated VO2(+) ion. Consistent with the EXAFS data, CCSD(T) calculations predict higher stability of the distorted octahedral geometry of VO2(+)(H2O)4 compared to the five-coordinate complex with a single water molecule in the second hydration shell, while all seven tested DFT methods yield the reverse stability of the two conformations. Analysis of the relative stabilities of formate-VO2(+) complexes indicates that both monodentate and bidentate forms may coexist in thermodynamic equilibrium in solution. Investigations of VO2(+) coordination with the formamidoximate anion has revealed the existence of seven possible binding motifs, four of which are within ~4.0 kcal mol(-1) of each other. Calculations establish that the most stable binding motif entails the coordination of oxime oxygen and amide nitrogen atoms via a tautomeric rearrangement of amidoxime to imino hydroxylamine. The difference in the most stable VO2(+) and UO2(2+) binding conformation has important implications for the design of more selective UO2(2+) ligands. PMID- 26559446 TI - Being positive despite illness: The contribution of positivity to the quality of life of cancer patients. AB - OBJECTIVE: The purpose of this study was to examine the longitudinal relationship between Positivity (POS), defined as a stable disposition to view at experience under a positive outlook, and physical and psychological functioning in a sample of cancer patients immediately after diagnosis and one year later. METHODS: A total of 110 patients (40% males) with pulmonary, colorectal and breast cancer, aged 30-75 (M age = 59.62; SD = 10.33), have been prospectively enrolled between 2012 and 2013, at the S. Andrea Hospital in Rome. All patients were previously aware of their diagnosis. A follow-up one year after diagnosis was conducted. We used structural equation modeling in order to analyse the specific effects of POS on functioning impairment from diagnosis to follow up. RESULTS: POS was associated with less functioning impairment both at diagnosis and follow-up assessments. Furthermore, POS level at diagnosis continued to be associated with less functioning impairment one year later, after controlling for its stability. CONCLUSIONS: Patients with higher level of POS tended to report less symptoms associated with negative affect such as anxiety and despondency and to preserve their habitual relationships and social roles. POS may act as a basic disposition that sustains patients' efforts to deal efficaciously with severe illness, by complying with medical treatment and using cognitive strategies that enable individuals to cope with concurrent and prospective challenges of illness. PMID- 26559447 TI - Cycling Time Trial Is More Altered in Hypobaric than Normobaric Hypoxia. AB - PURPOSE: Slight physiological differences between acute exposure in normobaric hypoxia (NH) and hypobaric hypoxia (HH) have been reported. Taken together, these differences suggest different physiological responses to hypoxic exposure to a simulated altitude (NH) versus a terrestrial altitude (HH). For this purpose, in the present study, we aimed to directly compare the time-trial performance after acute hypoxia exposure (26 h, 3450 min) by the same subjects under three different conditions: NH, HH, and normobaric normoxia (NN). Based on all of the preceding studies examining the differences among these hypoxic conditions, we hypothesized greater performance impairment in HH than in NH. METHODS: The experimental design consisted of three sessions: NN (Sion: FiO2, 20.93), NH (Sion, hypoxic room: FiO2, 13.6%; barometric pressure, 716 mm Hg), and HH (Jungfraujoch: FiO2, 20.93; barometric pressure, 481 mm Hg). The performance was evaluated at the end of each session with a cycle time trial of 250 kJ. RESULTS: The mean time trial duration in NN was significantly shorter than under the two hypoxic conditions (P < 0.001). In addition, the mean duration in NH was significantly shorter than that in HH (P < 0.01). The mean pulse oxygen saturation during the time trial was significantly lower for HH than for NH (P < 0.05), and it was significantly higher in NN than for the two other sessions (P < 0.001). CONCLUSION: As previously suggested, HH seems to be a more stressful stimulus, and NH and HH should not be used interchangeability when endurance performance is the main objective. The principal factor in this performance difference between hypoxic conditions seemed to be the lower peripheral oxygen saturation in HH at rest, as well as during exercise. PMID- 26559448 TI - Effects of Sprint Interval Cycling on Fatigue, Energy, and Cerebral Oxygenation. AB - INTRODUCTION: Feelings of fatigue are reduced after a session of continuous exercise of low-to-moderate intensity lasting 20 min or more, but only when feelings of energy are increased. Feelings of fatigue and energy have not been described after fatiguing, high-intensity interval exercise. Cerebral oxygenation has been implicated as a central correlate of fatigability, but it has not been studied concurrent with perceived fatigue during or after exercise. METHODS: Fifteen recreationally active participants (8 women, 7 men) completed bouts of sprint interval cycling (four, 30-s all-out sprints each followed by 4 min of active recovery) and a time- and work-matched bout of constant resistance cycling. Oxygenation (oxygenated hemoglobin [HbO2]) and deoxygenation (deoxygenated hemoglobin [HHb]) in the dorsolateral prefrontal cortex were measured using near-infrared spectroscopy. Fatigue ratings during each sprint and feelings of fatigue and energy during recovery were assessed. RESULTS: Increases in HbO2 and HHb in frontal cortex were greater during sprint cycling than during constant resistance cycling (P = 0.001). Fatigability (decreased power output) increased over successive sprints (P = 0.001). About 95% of the increase in fatigue ratings across sprints (P < 0.001) was accounted for by fatigability and cortical HbO2. Feelings of fatigue were decreased (P < 0.001) and feelings of energy were increased (P < 0.05) across sprint recovery periods but were unchanged during constant resistance cycling. About 85% of the changes in feelings of fatigue or energy during recovery were explained by fatigue ratings across sprints and maximum HbO2 in the cortex during recovery. CONCLUSION: Repeated, high-intensity sprints were fatiguing, but paradoxical reductions in feelings of fatigue and increases in feelings of energy occurred during recovery that were accounted for by ratings of fatigue during exercise and oxygenation in the dorsolateral prefrontal cortex during recovery. PMID- 26559449 TI - Exercise and Preexercise Nutrition as Treatment for McArdle Disease. AB - McArdle disease is due to an inborn defect in the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), the enzyme that catalyzes the first step of glycogenolysis. This condition is still not fully understood, and although advances in research would help patients immeasurably, these would also enhance our understanding of exercise metabolism. It has been 10 yr since the first published report demonstrating the benefits of regular aerobic exercise for these patients. However, misconceptions remain and the value of exercise prescription for patients with McArdle disease is still overlooked. Here, we review the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits. PMID- 26559450 TI - Hemodynamic Responses to Resistance Exercise in Patients with Coronary Artery Disease. AB - PURPOSE: Investigate hemodynamic responses of resistance exercise (RE) with moderate load (i.e., international guidelines for RE of patients) versus RE with high load in patients with coronary artery disease (CAD). METHODS: Medically stable male (n = 11) and female patients (n = 4) treated with PCI or percutaneous coronary intervention, or coronary artery bypass surgery a minimum of 6 months before this study, performed three sets of 15RM and 4RM RE in a randomized order on separate days. Beat-to-beat systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) were monitored at preexercise, and continuously during RE. RESULTS: Compared with preexercise, SBP and DBP (mean of three sets) increased by 12% to 13% (both; P < 0.001) and 35% to 40% after 15RM RE (both; P < 0.001). 15RM SBP and DBP were higher than 4RM SBP and DBP (both; P < 0.001). The SBP of the fourth repetition of 15 RM RE was similar to the SBP of the fourth repetition of 4RM RE. Compared with preexercise, SV increased moderately after 4RM and 15 RM RE, respectively (both, P < 0.001). HR increased more after 15RM compared with 4RM RE (P < 0.05); thus, higher CO after 15RM (compared with 4RM RE; P < 0.05) was mainly caused by higher HR. SVR decreased by 15% (P < 0.001) and 50% (P < 0.01) after 4RM and 15RM RE. CONCLUSIONS: SBP and DBP increased significantly more during moderate load RE; thus, the magnitude of the external load is not the prime determinant of the pressure response during RE. If management of blood pressure is of concern, high load/low rep RE is preferable to medium load/high rep RE. PMID- 26559451 TI - Sedentary Sphere: Wrist-Worn Accelerometer-Brand Independent Posture Classification. AB - INTRODUCTION: Access to raw acceleration data should facilitate comparisons between accelerometer outputs regardless of monitor brand. PURPOSE: To evaluate the accuracy of posture classification using the Sedentary Sphere in data from two widely used wrist-worn triaxial accelerometers. METHODS: Laboratory: Thirty four adults wore a GENEActiv and an ActiGraph GT3X+ on their nondominant wrist while performing four lying, seven sitting, and five upright activities. Free living: The same participants wore both accelerometers on their nondominant wrist and an activPAL3 on their right thigh during waking hours for 2 d. RESULTS: Laboratory: Using the Sedentary Sphere with 15-s epoch GENEActiv data, sedentary and upright postures were correctly identified 74% and 91% of the time, respectively. Corresponding values for the ActiGraph data were 75% and 90%. Free living: Total sedentary time was estimated at 534 +/- 144, 523 +/- 143, and 528 +/- 137 min by the activPAL, the Sedentary Sphere with GENEActiv data and with ActiGraph data, respectively. The mean bias, relative to the activPAL, was small with moderate limits of agreement (LoA) for both the GENEActiv (mean bias = -12.5 min, LoA = -117 to 92 min) and ActiGraph (mean bias = -8 min, LoA = -103 to 88 min). Strong intraclass correlations (ICC) were evident for the activPAL with the GENEActiv (0.93, 0.84-0.97 (95% confidence interval) and the ActiGraph (0.94, 0.86-0.97). Agreement between the GENEActiv and ActiGraph posture classifications was very high (ICC = 0.98 (0.94-0.99), mean bias = +3 min, LoA = -58 to 63 min). CONCLUSIONS: These data support the efficacy of the Sedentary Sphere for classification of posture from a wrist-worn accelerometer in adults. The approach is equally valid with data from both the GENEActiv and ActiGraph accelerometers. PMID- 26559452 TI - Risk Factors for Knee Injuries in Children 8 to 15 Years: The CHAMPS Study DK. AB - INTRODUCTION: Knee injuries are frequent in children, with most studies reporting traumatic knee injuries. Evidence of risk factors for knee injuries in children is sparse. The purpose of this study was to report the extent of traumatic and overuse knee injuries in children and to evaluate intrinsic and extrinsic factors for risk of these injuries. METHODS: Weekly musculoskeletal pain, sport participation, and sports type were reported by 1326 school children (8-15 yr). Knee injuries were classified as traumatic or overuse. Multinomial logistic regression was used for analyses. RESULTS: During the study period, 952 (15% traumatic and 85% overuse) knee injuries were diagnosed. Period prevalence for traumatic and overuse knee injuries were 0.8/1000 and 5.4/1000 sport participations, respectively. Participation in tumbling gymnastics was a risk factor for traumatic knee injuries (OR, 2.14). For overuse knee injuries, intrinsic risk factors were sex (girls OR, 1.38) and previous knee injury (OR, 1.78), whereas participation in soccer (OR, 1.64), handball (OR, 1.95), basket (OR, 2.07), rhythmic (OR, 1.98), and tumbling gymnastics (OR, 1.74) were additional risk factors. For both injury types, sport participation above two times per week increased odds (OR, 1.46-2.40). CONCLUSIONS: Overuse knee injuries were the most frequent injury type. For traumatic knee injuries, participation in tumbling gymnastics was a risk factor. Risk factors for overuse knee injuries were being a girl; previous knee injury; and participation in soccer, handball, basket, and rhythmic and tumbling gymnastics. Further risk factors for both types of injury were participation in sports above two times per week. Although growth related overuse knee injuries are a self-limiting condition, a major part of children are affected by these injuries with unknown short- and long-term consequences. PMID- 26559453 TI - Muscle Activity during Rapid Wrist Extension in People with Lateral Epicondylalgia. AB - BACKGROUND: Individuals with lateral epicondylalgia (LE) have delayed upper limb reaction time (RT); however, it is unknown if the mechanisms of this dysfunction are related to neural processing or the affected forearm muscles. The aim of this study was to examine the timing of processes that occur before and after forearm muscles are activated during the RT task. METHODS: Eleven LE (42 +/- 11 yr) and 11 healthy controls (42 +/- 11 yr) performed rapid wrist extension in response to an audio cue. Intramuscular EMG was obtained from extensor carpi radialis brevis (ECRB), extensor digitorum communis (EDC), extensor carpi ulnaris (ECU), and anconeus. Premotor time (PMT) was the duration from an audio cue to the onset of muscle activity, and motor time (MT) was the onset of muscle activity to the onset of wrist extension. Standard clinical assessments of LE were also performed. RESULTS: RT was significantly slower (33; 95% CI, 1-66 ms) in the LE group. There were no group differences in PMT and the order of muscle activation. Instead, the MT of ECRB (18; 95% CI, 6-31 ms), EDC (12; 95% CI, 1-23 ms), ECU (28; 95% CI, 9-46 ms), and anconeus (33; 95% CI, 11-56 ms) showed significant delay in LE group. Regression analyses revealed that the duration of LE could predict RT, ECRB, and anconeus PMT, whereas cold pain threshold predicted ECRB MT. CONCLUSIONS: Delayed RT in LE was predominantly caused by deficits in ECRB and EDC MT. This study provides preliminary evidence that in the people with longer LE symptoms, duration appeared to have faster RT, although confirmation of this finding is required before firm conclusions can be drawn. PMID- 26559454 TI - Displacing Sedentary Time: Association with Cardiovascular Disease Prevalence. AB - PURPOSE: Isotemporal substitution analysis offers new insights for public health but has only recently been applied to sedentary behavior research. We aimed to quantify associations between the substitution of 10 min of sedentary behavior with 10 min of light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) and the prevalence of cardiovascular disease (CVD). Age was also explored as a potential effect modifier. METHODS: We completed a secondary analysis of data from 1477 adults from the Health Survey for England (2008). Sedentary time, LPA, and MVPA were measured using accelerometry. We applied isotemporal models to quantify the relationship with CVD prevalence of replacing 10 min of sedentary time with equivalent amounts of LPA or MVPA. Prevalence risk ratios (RR) with 95% confidence intervals (CI) are presented, adjusted for covariates. The role of age as an effect modifier was explored via age-MVPA and age-LPA interactions. CVD was defined as per the International Classification of Diseases. RESULTS: The prevalence of CVD was 24%. The RR was 0.97 (95% CI, 0.96 0.99) for LPA and 0.88 (0.81-0.96) for MVPA. Substitution of approximately 50 min of LPA would be required for an association equivalent to 10 min of MVPA. The beneficial association of MVPA was attenuated with age, with a decrease in the relative risk reduction of approximately 7% per decade. CONCLUSIONS: Isotemporal substitution of sedentary time with LPA was associated with a trivial relative risk reduction for CVD, whereas the equivalent replacement with MVPA had a small beneficial relationship. With respect to CVD prevalence, MVPA might become decreasingly important in older individuals. Prospective studies are needed to investigate causality. PMID- 26559456 TI - Vaccines for tick-borne diseases and cost-effectiveness of vaccination: a public health challenge to reduce the diseases' burden. AB - Tick-borne encephalitis (TBE) and Lyme borreliosis (LB) are tick-borne diseases (TBDs), and both present an increasing burden worldwide. Vaccination as public health intervention could be the most effective way to reduce this burden. TBE vaccines are available, but vaccines against LB are still in the phase of development. At the European level, TBE vaccines are likely under-administered to effectively prevent the disease. Cost-effectiveness of vaccination is a helpful tool in the decision making process to include novel vaccines in the national vaccination program or to extend current programs, and its role is only increasing. Cost-effectiveness studies on TBE vaccines have been performed in Slovenia, Sweden, Finland and Estonia so far. Cost-effectiveness studies with the novel vaccines against LB are expected to be performed in the near future. PMID- 26559455 TI - Effects of Pedal Speed and Crank Length on Pedaling Mechanics during Submaximal Cycling. AB - During submaximal cycling, the neuromuscular system has the freedom to select different intermuscular coordination strategies. From both a basic science and an applied perspective, it is important to understand how the central nervous system adjusts pedaling mechanics in response to changes in pedaling conditions. PURPOSE: To determine the effect of changes in pedal speed (a marker of muscle shortening velocity) and crank length (a marker of muscle length) on pedaling mechanics during submaximal cycling. METHODS: Fifteen trained cyclists performed submaximal isokinetic cycling trials (90 rpm, 240 W) using pedal speeds of 1.41 to 1.61 m.s(-1) and crank lengths of 150 to 190 mm. Joint powers were calculated using inverse dynamics. RESULTS: Increases in pedal speed and crank length caused large increases knee and hip angular excursions and velocities (P < 0.05), whereas ankle angular kinematics stayed relatively constant (P > 0.05). Joint moments and joint powers were less affected by changes in the independent variables, but some interesting effects and trends were observed. Most noteworthy, knee extension moments and powers tended to decrease, whereas hip extension power tended to increase with an increase in crank length. CONCLUSIONS: The distribution of joint moments and powers is largely maintained across a range of pedaling conditions. The crank length induced differences in knee extension moments, and powers may represent a trade-off between the central nervous system's attempts to simultaneously minimize muscle metabolic and mechanical stresses. These results increase our understanding of the neural and mechanical mechanisms underlying multi-joint task performance, and they have practical relevance to coaches, athletes, and clinicians. PMID- 26559457 TI - Improving Diagnosis in Health Care--The Next Imperative for Patient Safety. PMID- 26559458 TI - Designing a better appraisal system that meets the needs of trainees and the public. PMID- 26559459 TI - HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib. AB - Human epidermal growth factor 2 (HER2, ERBB2) mutations in lung cancers are oncogenic drivers that respond to HER2 targeted therapies. Little is known about the sensitivity of subtypes of HER2 mutant lung cancers to targeted agents. We present a patient with HER2 mutant lung cancer with a 12 base pair insertion YVMA (p.A775_G776insYVMA), who had a long natural history and durable partial response to afatinib. We demonstrate that afatinib has activity in patients with HER2 mutant lung cancers with exon 20 YVMA insertions, the most common variant. PMID- 26559460 TI - Ten years later: Evaluation of the effectiveness of 12.5% amitraz against a field population of Rhipicephalus (Boophilus) microplus using field studies, artificial infestation (Stall tests) and adult immersion tests. AB - Using field trials, artificial infestations (Stall tests) and in vitro adult immersion tests, the present study evaluated the acaricidal efficacy of 12.5% amitraz administered via whole body spraying against a Rhipicephalus (Boophilus) microplus population that did not have any contact with chemical products belonging to this acaricide family for 10 years (approximately 40 generations). Two natural infestation trials, two artificial infestation trials (Stall tests) and two adult immersion tests were performed in two different stages in 2005 and 2015. Between 2002 and 2015, the bovine herd of this property was formed by approximately 450 animals from the Simmental breed that were divided into nine paddocks formed by Cynodon dactylon (L.) Pers. For the natural infestation experiments in 2005 and 2015, we selected nearly 70 animals naturally infested with ticks from the same herd that belonged to the "Sao Paulo" farm located in Sao Jose do Rio Pardo, Sao Paulo, Brazil. Field studies were performed in the same paddock (9). To evaluate anti-R. (B.) microplus activity in the artificially infested cattle (Stall tests) and adult immersion tests, two experiments of each methodology were performed at CPPAR (the Center of Research in Animal Health located on the FCAV/UNESP campus in Jaboticabal, Sao Paulo, Brazil) in 2005 and 2015. R. (B.) microplus used in the artificial infestation, and adult immersion test experiments were obtained from paddocks 1-9 in 2005 and 2015 from the commercial farm where the field studies were performed. Based on the obtained results, it was possible to conclude that amitraz use in rotation with pyrethroids every 28 days for three consecutive years (2002-2004) previous to the beginning of the first trial (2005) was sufficient to generate a R. (B.) microplus strain resistant to amitraz. Moreover, using field trials, artificial infestations (Stall tests) and adult immersion tests, we verified that 40 generations of the tick species with no contact to the aforementioned compound (amitraz) were not sufficient to revert or modify the efficacy/resistance of amitraz for this analyzed R. (B.) microplus strain. The reversion of amitraz efficacy values in R. (B.) microplus may only occur when resistance of the field strain is incipient. Alternatively, the differences in the results may be due to differences in the Rhipicephalus spp. species between current study locations. Therefore, future studies must be performed to prove this hypothesis. PMID- 26559461 TI - FGF10: A multifunctional mesenchymal-epithelial signaling growth factor in development, health, and disease. AB - The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and epithelium, respectively. FGF10 is a mesenchymal signaling molecule in the epithelium. FGF10 knockout mice die shortly after birth due to the complete absence of lungs as well as fore- and hindlimbs. FGF10 is also essential for the development of multiple organs. The phenotypes of Fgf10 knockout mice are very similar to those of FGFR2b knockout mice, indicating that FGF10 acts as a ligand that is specific to FGFR2b in mouse multi-organ development. FGF10 also plays roles in epithelial-mesenchymal transition, the repair of tissue injury, and embryonic stem cell differentiation. In humans, FGF10 loss-of-function mutations result in inherited diseases including aplasia of lacrimal and salivary gland, lacrimo-auriculo-dento-digital syndrome, and chronic obstructive pulmonary disease. FGF10 is also involved in the oncogenicity of pancreatic and breast cancers. Single nucleotide polymorphisms in FGF10 are also potential risk factors for limb deficiencies, cleft lip and palate, and extreme myopia. These findings indicate that FGF10 is a crucial paracrine signal from the mesenchyme to epithelium for development, health, and disease. PMID- 26559462 TI - Electromyographic assessment of forearm muscle function in tennis players with and without Lateral Epicondylitis. AB - There is no consensus about the main aetiology of Lateral Epicondylitis (LE) or Tennis Elbow. While electromyographic assessment of alterations in neuromuscular control and activation patterns of forearm muscles has received increasing interest as potential intrinsic factors in non-tennis players, there has been insufficient attention in tennis players. The purpose of present review was to search the literature for the electromyographic studies of forearm muscles in tennis players in order to (1) identify related implications for LE, (2) highlight key technical and methodological shortcomings, and (3) suggest potential pathways for future research. An electronic search of PubMed, Scopus, Web of Science, and Google Scholars (1980 to October 2014) was conducted. Titles, abstracts, and full-text articles were screened to identify "peer-reviewed" studies specifically looking into "electromyographic assessment of forearm muscles" in "tennis players". After screening 104 articles, 13 original articles were considered in the main review involving a total of 216 participants (78% male, 22% female). There were indications of increased wrist extensor activity in all tennis strokes and less experienced single-handed players, however with insufficient evidence to support their relationship with the development of LE. Studies varied widely in study population, sample size, gender, level of tennis skills, electrode type, forearm muscles studied, EMG recording protocol, EMG normalisation method, and reported parameters. As a result, it was not possible to present combined results of existing studies and draw concrete conclusions in terms of clinical implications of findings. There is a need for establishment of specific guidelines and recommendations for EMG assessment of forearm musculature particularly in terms of electrode and muscle selection. Further studies of both healthy controls and tennis players suffering from LE with adequate sample sizes and well-defined demographics are warranted. PMID- 26559463 TI - Factors to consider in identifying critical points in lumbar spine flexion relaxation. AB - Flexion relaxation (FR), a myoelectric silence of extensor muscles near end range of lumbar flexion, is commonly reported as the lumbar flexion angle at the instant the extensor muscles become silent. However, lumbar flexion angle alone is insufficient to characterize mechanisms that modulate FR. As FR requires the moment generated by passive lumbar extensor tissues to equilibrate the moment due to gravity, the inter-relationships between lumbar moment, flexion angle, and myoelectrical silence will provide added information in the understanding of FR. The purpose of this study was to examine the relationship between lumbar moment and flexion angle throughout various flexion manoeuvres. It was hypothesized that lumbar moment and flexion angle would not be linearly related and would be affected by lower limb position, range of motion, and the addition of mass to the torso. Eleven participants performed four different lumbar flexion trials. Results showed that lumbar flexion was correlated with the lumbar moment (r = 0.92); however an analysis of residuals found that these measures were not linearly related. The moment was, however, correlated (r = 0.99) and linearly related to the sine of trunk inclination (T12 rigid body with respect to global horizontal). Future studies of FR could use trunk inclination as a simple kinematic measure to predict relative changes in lumbar moment with flexion. PMID- 26559464 TI - Obesity is associated with prolonged activity of the quadriceps and gastrocnemii during gait. AB - PURPOSE: To examine the effect of obesity and its potential interaction with knee OA presence on the electromyography patterns of the major knee joint periarticular muscles during walking. SCOPE: One hundred and eighteen asymptomatic adults and 177 adults with moderate knee osteoarthritis were subdivided into categories of healthy weight (n = 77; 20 kg/m(2) < BMI < 25 kg/m(2)), overweight (n = 117; 25 kg/m(2) ? BMI < 30 kg/m(2)), and obese (n = 101; BMI ? 30 kg/m(2) based on their body mass index (BMI). All individuals underwent a three-dimensional gait analysis. Surface electromyograms from the lateral and medial gastrocnemii, lateral and medial hamstrings, vastus lateralis, vastus medialis, and rectus femoris were recorded during self-selected speed walking. Principal component analysis was used to extract major features of amplitude and temporal pattern variability from the electromyograms of each muscle group (gastrocnemii, quadriceps, hamstrings separately). Analysis of variance models tested for main BMI category effects and interaction effects for these features (alpha = 0.05). Statistically significant BMI category (i.e. obesity) effects were found for features that described more prolonged activations of the gastrocnemii and quadriceps muscles during the stance phase of gait with obesity (P < 0.05). CONCLUSIONS: Obesity was associated with prolonged activation of quadriceps and gastrocnemii, which can result in prolonged knee joint contact loading, and thereby may contribute to the predisposition of knee OA development and progression in obese individuals. PMID- 26559465 TI - Loss resilience for two-qubit state transmission using distributed phase sensitive amplification. AB - We transmit phase-encoded non-orthogonal quantum states through a 5-km long fibre based distributed optical phase-sensitive amplifier (OPSA) using telecom wavelength photonic qubit pairs. The gain is set to equal the transmission loss to probabilistically preserve input states during transmission. While neither state is optimally aligned to the OPSA, each input state is equally amplified with no measurable degradation in state quality. These results promise a new approach to reduce the effects of loss by encoding quantum information in a two qubit Hilbert space which is designed to benefit from transmission through an OPSA. PMID- 26559467 TI - Pregnancy outcomes using stallion epididymal sperm stored at 5 degrees C for 24 or 48 hours before harvest. AB - The cryopreservation of epididymal sperm can be useful in a variety of circumstances for ensuring genetic preservation of a valued stallion. Although early studies have reported pregnancy rates significantly lower than those achieved with cryopreserved ejaculated sperm, two recent studies report over 60% one-cycle pregnancy rates with epididymal sperm stored for 24 hours at 5 degrees C before harvest and cryopreservation. The aims of this study were to: (1) attempt to replicate the one-cycle pregnancy rate of over 60% using epididymal sperm cooled and stored within the epididymis for 24 hours before harvest and cryopreservation and (2) evaluate pregnancy outcome with sperm cooled and stored within the epididymis for 48 hours before sperm harvest and cryopreservation. Testicles were obtained from 13 stallions undergoing routine castration. The epididymides were stored at 5 degrees C for either 24 or 48 hours before sperm harvest and cryopreservation in an egg yolk and dimethylformamide-based freezing extender. Thirteen mares were bred on one cycle with cryopreserved epididymal sperm stored for 24 hours before harvest, and 10 of those 13 mares were also bred on a previous or subsequent cycle with samples from the same stallion that had been stored for 48 hours before harvest. Pregnancy occurred in 7 of the 13 inseminations of sperm stored for 24 hours before harvest, and in 4 of the 10 inseminations of sperm stored for 48 hours before harvest. The pregnancy rate using epididymal sperm stored for 24 hours before harvest is consistent with that of previous reports. In addition, these results provide evidence that pregnancies can be achieved when the epididymides are cooled and stored for 48 hours before sperm harvest and cryopreservation. PMID- 26559466 TI - Deceleration of single-stranded DNA passing through a nanopore using a nanometre sized bead structure. AB - DNA sequencing with a solid-state nanopore requires a reduction of the translocation speeds of single-stranded DNA (ssDNA) over 10 MUs/base. In this study, we report that a nanometre-sized bead structure constructed around a nanopore can reduce the moving speed of ssDNA to 270 MUs/base by adjusting the diameter of the bead and its surface chemical group. This decelerating effect originates from the strong interaction between ssDNA and the chemical group on the surface of the bead. This nanostructure was simply prepared by dip coating in which a substrate with a nanopore was immersed in a silica bead solution and then dried in an oven. As compared with conventional approaches, our novel method is less laborious, simpler to perform and more effective in reducing ssDNA translocation speed. PMID- 26559468 TI - Form of supplemental selenium fed to cycling cows affects systemic concentrations of progesterone but not those of estradiol. AB - In areas where soils are deficient in selenium (Se), dietary supplementation of this trace mineral directly to cattle is recommended. Selenium status affects fertility, and the form of Se supplemented to cows affects tissue-specific gene expression profiles. The objective of this study was to determine whether the form of Se consumed by cows would affect follicular growth and the production of steroids. Thirty-three Angus-cross cows that had ad libitum access of a mineral mix containing 35 ppm of Se in free-choice vitamin-mineral mixes as either inorganic (ISe), organic (OSe), or a 50/50 mix of ISe and OSe (MIX) for 180 days were used. After 170 days of supplementation, all cows were injected with 25-mg PGF2alpha to induce regression of the CL and then monitored for behavioral estrus (Day 0). From Day 4 to Day 8 after estrus, follicular growth was determined by transrectal ultrasonography. On Day 6, cows were injected with PGF2alpha (20 then 15 mg, 8-12 hours apart) to induce regression of the developing CL and differentiation of the dominant follicle of the first follicular wave into a preovulatory follicle. On Day 8, 36 hours after PGF2alpha (20 mg), the contents of the preovulatory follicle were aspirated by ultrasound-guided follicular puncture. Blood collected on Days 6 and 8 and follicular fluid collected on Day 8 was analyzed for concentrations of progesterone and estradiol. Form of Se supplemented to cows affected (P = 0.04) the systemic concentration of progesterone on Day 6, but not on Day 8. Form of Se did not affect the systemic concentration of estradiol on Day 6 or Day 8. Form of Se tended to affect (P = 0.07) the concentration of progesterone, but not that of estradiol, in the follicular fluid. Form of Se did not affect diameter of the dominant ovarian follicle on Days 4 to 6, but tended to affect (P = 0.08) the diameter of the preovulatory follicle on Day 8. Our results suggest that form of Se fed to cows affects the production of progesterone but not that of estradiol. Further investigation of organic Se-induced increases in progesterone and potentially the effects of increased progesterone on the establishment of pregnancy, especially in cows of lower fertility, is warranted. PMID- 26559469 TI - Gene expression profiles of some cytokines, growth factors, receptors, and enzymes (GM-CSF, IFNgamma, MMP-2, IGF-II, EGF, TGF-beta, IGF-IIR) during pregnancy in the cat uterus. AB - Early pregnancy is one of the most critical periods of pregnancy, and many factors such as cytokines, enzymes, and members of the immune system have to cooperate in a balanced way. In the present study, the gene expression profiles of factors associated with pregnancy such as EGF, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, interferon gamma, insulin like growth factor 2, insulin-like growth factor 2 receptor, and matrix metalloproteinase 2 were analyzed in uterine tissues of female cats. The cats were assigned to five groups: G1 (embryo positive, n = 7; 7th day after mating), G2 (after implantation, n = 7; 20th day after mating), G3 (midgestation, n = 7; 24-25th day after mating), G4 (late gestation, n = 7; 30-45th day after mating), G5 (oocyte group, n = 7; 7th day after estrus). Tissue samples from the uterus and placenta were collected after ovariohysterectomy. Relative messenger RNA levels were determined by real-time polymerase chain reaction. All the factors examined were detected in all tissue samples. In the course of pregnancy, significantly higher expression of EGF and matrix metalloproteinase 2 in G2 than in G1 was observed (P < 0.05). Insulin-like growth factor 2 expression was higher in all groups than in G1 (P < 0.05). Upregulation of EGF during implantation was detected. The expression of interferon gamma was significantly higher in G3 than in G1 (P < 0.05). Transforming growth factor beta and granulocyte-macrophage colony-stimulating factor were constantly expressed in all groups. In conclusion, the expressions of these factors in feline uterine tissue at different stages of pregnancy might indicate that these factors play roles in the development of pregnancy such as trophoblast invasion, vascularization, implantation, and placentation. PMID- 26559470 TI - Treatment with protein kinase C activator is effective for improvement of male pronucleus formation and further embryonic development of sperm-injected oocytes in pigs. AB - To assist the process of oocyte activation, which is essential for promotion of fertilization events, i.e., resumption of meiosis, extrusion of the second polar body and formation of the pronucleus (PN), artificial stimuli such as an electrical pulse have been applied to porcine oocytes after injection of sperm. However, the efficiency of fertilization and embryonic development remains low. It is well known that in vertebrates, inactivation of mitogen-activated protein (MAP) kinase is required for oocyte activation. We have hypothesized that even after electrical stimulation of sperm-injected oocytes, MAP kinase may not be inactivated. As it has been reported that MAP kinase activity is regulated by protein kinase C, we examined the effectiveness of phorbol 12-myristate 13 acetate (PMA), a protein kinase C activator, for improvement of fertilization and embryonic development of sperm-injected porcine oocytes. First, we examined the concentrations (0, 0.01, 0.1, 1, and 10 MUM) and durations (0, 1, 3, 5 hours) of PMA treatment that were efficient for the extrusion of two polar bodies and formation of two PNs (2PB+2PN) and embryonic development. When the sperm-injected oocytes were treated with 0.01-MUM PMA for 3 hours after electrical stimulation, the rates of 2PB+2PN and embryonic development were higher than those in the other treatment groups. We then examined the effect of PMA treatment (0.01 MUM, 3 hours) on MAP kinase activity. Unexpectedly, after electrical stimulation, the activity remained low until PN formation, irrespective of whether or not the oocytes had been treated with PMA. On the other hand, transformation of the injected sperm nucleus into the male PN was accelerated after the PMA treatment. Our present results suggest that the low efficiency of fertilization and embryonic development in sperm-injected oocytes is not due to high activity of MAP kinase but due to poor transformation of the injected sperm nucleus into the male PN. Furthermore, a combination of electrical stimulation and PMA is a fairly effective artificial protocol for promoting 2PB+2PN and embryonic development in sperm-injected porcine oocytes. PMID- 26559471 TI - The birth of a giant panda: Tracking the biological factors that successfully contribute to conception through to postnatal development. AB - Reproducing giant pandas (Ailuropoda melanoleuca) remains the most challenging aspect of managed care of this species. However, advancement in knowledge stemming from basic science research on the giant panda has facilitated a growth in the population. Here, we report the successful application of reproductive technologies, including noninvasive hormone monitoring, behavioral/morphometric observations, ultrasonographic evaluations, and acute phase protein assessment, in an individual female. By applying these approaches to one female, we report the practicality and usefulness of a multidisciplinary approach to reproductive care of the species. In addition, the utilization of various technologies across multiple physiological states also provided us an opportunity to record previously understudied events, such as maternal response to weaning and growth of a conceptus. PMID- 26559472 TI - Modeling human target reaching with an adaptive observer implemented with dynamic neural fields. AB - Humans can point fairly accurately to memorized states when closing their eyes despite slow or even missing sensory feedback. It is also common that the arm dynamics changes during development or from injuries. We propose a biologically motivated implementation of an arm controller that includes an adaptive observer. Our implementation is based on the neural field framework, and we show how a path integration mechanism can be trained from few examples. Our results illustrate successful generalization of path integration with a dynamic neural field by which the robotic arm can move in arbitrary directions and velocities. Also, by adapting the strength of the motor effect the observer implicitly learns to compensate an image acquisition delay in the sensory system. Our dynamic implementation of an observer successfully guides the arm toward the target in the dark, and the model produces movements with a bell-shaped velocity profile, consistent with human behavior data. PMID- 26559473 TI - Improvement in Mouse iPSC Induction by Rab32 Reveals the Importance of Lipid Metabolism during Reprogramming. AB - Induced pluripotent stem cells (iPSCs) have variable expression levels of a series of genes that affect their pluripotent potential, but the regulatory mechanisms controlling reprogramming remain unclear. By testing the efficiency of iPSC generation using Oct4, Sox2, Klf4 (termed OSK) plus one additional gene, we found that Rab32 improved reprogramming efficiency. We established a system for detecting the number and the size of lipid droplets and autophagosomes per cell for tracking their morphological changes during reprogramming. Our results showed that Rab32 increased lipid storage during the early and middle stages, and also increased autophagy during the middle stage of reprogramming. These findings were further confirmed by the up-regulation of lipid biosynthesis and autophagosome formation related genes, of which their expression could improve iPSC induction. The inhibition of lipid biosynthesis and autophagosome formation significantly reduced reprogramming efficiency, and the inhibition of lipid synthesis phenotype could be rescued by the overexpression of Rab32. In addition, the expression of pluripotency genes such as Klf2, Nr5a2 and Tbx3, was up-regulated by Rab32. These results demonstrated that Rab32 could improve the induction of iPSCs through the enhancement of lipid biosynthesis, highlighting the importance of lipid metabolism during reprogramming. PMID- 26559474 TI - Laterality effects in functional connectivity of the angular gyrus during rest and episodic retrieval. AB - INTRODUCTION: The angular gyrus (AG) is consistently reported in neuroimaging studies of episodic memory retrieval and is a fundamental node within the default mode network (DMN). Its specific contribution to episodic memory is debated, with some suggesting it is important for the subjective experience of episodic recollection, rather than retrieval of objective episodic details. Across studies of episodic retrieval, the left AG is recruited more reliably than the right. We explored functional connectivity of the right and left AG with the DMN during rest and retrieval to assess whether connectivity could provide insight into the nature of this laterality effect. METHODS: Using data from the publically available 1000 Functional Connectome Project, 8min of resting fMRI data from 180 healthy young adults were analysed. Whole-brain functional connectivity at rest was measured using a seed-based Partial Least Squares (seed-PLS) approach (McIntosh and Lobaugh, 2004) with bilateral AG seeds. A subsequent analysis used 6-min of rest and 6-min of unconstrained, silent retrieval of autobiographical events from a new sample of 20 younger adults. Analysis of this dataset took a more targeted approach to functional connectivity analysis, consisting of univariate pairwise correlations restricted to nodes of the DMN. RESULTS: The seed-PLS analysis resulted in two Latent Variables that together explained ~86% of the shared cross-block covariance. The first LV revealed a common network consistent with the DMN and engaging the AG bilaterally, whereas the second LV revealed a less robust, yet significant, laterality effect in connectivity - the left AG was more strongly connected to the DMN. Univariate analyses of the second sample again revealed better connectivity between the left AG and the DMN at rest. However, during retrieval the left AG was more strongly connected than the right to non-medial temporal (MTL) nodes of the DMN, and MTL nodes were more strongly connected to the right AG. DISCUSSION: The multivariate analysis of resting connectivity revealed that the left and right AG show similar connectivity with the DMN. Only after accounting for this commonality were we able to detect a left laterality effect in DMN connectivity. Further probing with univariate connectivity analyses during retrieval demonstrates that the left preference we observe is restricted to the non-MTL regions of the DMN, whereas the right AG shows significantly better connectivity with the MTL. These data suggest bilateral involvement of the AG during retrieval, despite the focus on the left AG in the literature. Furthermore, the results suggest that the contribution of the left AG to retrieval may be separable from that of the MTL, consistent with a role for the left AG in the subjective aspects of recollection in memory, whereas the MTL and the right AG may contribute to objective recollection of specific memory details. PMID- 26559475 TI - The Role of Insulin-Like Growth Factor Binding Protein 2 (IGFBP2) in the Regulation of Corneal Fibroblast Differentiation. AB - PURPOSE: Previously, we reported that keratocyte-conditioned medium (KCM) facilitates the differentiation of human mesenchymal stem cells (hMSCs) into corneal keratocyte-like cells. This study is designed to investigate the roles of insulin-like growth factor binding protein 2 (IGFBP2) for the regulation of corneal fibroblast differentiation as a newly unveiled component of KCM. METHODS: Immunodot blot analysis was performed to identify the factors that are highly secreted, especially in KCM. Then, we investigated whether IGFBP2 differentiates hMSCs into keratocyte-like cells and whether maintains the phenotypes of keratocyte in human corneal fibroblasts (HCFs) by analyzing expression patterns of alpha-smooth muscle actin (alpha-SMA) and keratocyte markers including keratocan, lumican and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). Furthermore, to specify the role of IGFBP2, the expression of alpha-SMA and keratocyte markers was determined in transforming growth factor beta 1 (TGFbeta1) induced corneal myofibroblast and in HCFs after knockdown of IGFBP2. RESULTS: The most prominent factor in both KCM and amniotic membrane extract was IGFBP2. Insulin-like growth factor binding protein 2 increased the expression of IGFBP2, keratocan, and ALDH1A1, and decreased alpha-SMA expression in hMSCs and HCFs. Insulin-like growth factor binding protein 2 inhibited TGFbeta1-induced upregulation of alpha-SMA and increased expressions of keratocan and ALDH1A1 in HCFs. Furthermore, the knockdown of IGFBP2 increased alpha-SMA expression and decreased ALDH1A1 level in HCFs. CONCLUSIONS: Insulin-like growth factor binding protein 2 is strongly associated with restoration of keratocyte phenotype in HCFs. Our results show an important novel role of IGFBP2 in regulation of corneal fibroblast differentiation and suggest that IGFBP2 can be a therapeutic candidate for corneal antifibrotic strategy. PMID- 26559477 TI - Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED). AB - PURPOSE: Palate Lung Nasal Clone (PLUNC) is a hydrophobic protein belonging to the family of surfactant proteins that is involved in fluid balance regulation of the lung. Moreover, it is known to directly act against gram-negative bacteria. The purpose of this study was to investigate the possible expression and antimicrobial role of PLUNC at the healthy ocular surface and in tears of patients suffering from dry eye disease (DED). METHODS: Bioinformatics and biochemical and immunologic methods were combined to elucidate the structure and function of PLUNC at the ocular surface. Tissue-specific localization was performed by using immunohistochemistry. The PLUNC levels in tear samples from non-Sjogren's DED patients with moderate dry eye suffering either from hyperevaporation or tear deficiency were analyzed by ELISA and compared with tears from healthy volunteers. RESULTS: Palate Lung Nasal Clone is expressed under healthy conditions at the ocular surface and secreted into the tear film. Protein modeling studies and molecular dynamics simulations performed indicated surface activity of PLUNC. In vitro experiments revealed that proinflammatory cytokines and bacterial supernatants have only a slight effect on the expression of PLUNC in HCE and HCjE cell lines. In tears from DED patients, the PLUNC concentration is significantly increased (7-fold in evaporative dry eye tears and 17-fold in tears from patients with tear deficiency) compared with healthy subjects. CONCLUSIONS: The results show that PLUNC is a protein of the tear film and suggest that it plays a role in fluid balance and surface tension regulation at the ocular surface. PMID- 26559476 TI - Blood-Retinal Barrier Compromise and Endogenous Staphylococcus aureus Endophthalmitis. AB - PURPOSE: To test the hypothesis that blood-retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis. METHODS: To compromise the blood-retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus-induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti-ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays. RESULTS: We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 * 103 +/- 1.78 * 102 cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 * 102 +/- 7.09 * 102 cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 * 102 +/- 2.49 * 102 cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 * 102 +/- 1.08 * 103 cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier. CONCLUSIONS: Taken together, these results indicated that S. aureus is capable of inducing blood-retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals. PMID- 26559478 TI - Membrane Peeling-Induced Retinal Alterations on Intraoperative OCT in Vitreomacular Interface Disorders From the PIONEER Study. AB - PURPOSE: To assess retinal architectural alterations that occur following membrane peeling procedures and the impact of peel technique on these alterations utilizing intraoperative optical coherence tomography (iOCT). METHODS: This is a subanalysis of the prospective PIONEER iOCT study of eyes undergoing a membrane peeling for a vitreomacular interface (VMI) disorder. Intraoperative scanning was performed with a microscope-mounted OCT system. Macroarchitectural alterations (e.g., full-thickness retinal elevations) and microarchitectural alterations (e.g., relative layer thickness alterations) were analyzed. Video/iOCT correlation was performed to identify instrument-tissue manipulations resulting in macroarchitectural alterations. RESULTS: One hundred sixty-three eyes were included in the macroarchitectural analysis. Instrumentation utilized for membrane peeling included forceps alone for 73 eyes (45%), combined diamond dusted membrane scraper (DDMS) and forceps for 87 eyes (53%), and other techniques in three eyes (2%). Focal retinal elevations were identified in 45 of 163 eyes (28%). Video/iOCT correlation identified 69% of alterations involved forceps compared to 26% due to DDMS. Sixteen percent of retinal alterations persisted 1 month following surgery. The microarchitectural analysis included 134 eyes. Immediately following membrane peeling, there was a significant increase in the ellipsoid zone to retinal pigment epithelium height (+20%, P < 0.00001) and the cone outer segment tips to retinal pigment epithelium height (+18%, P < 0.00001). CONCLUSIONS: Significant subclinical retinal architectural changes occur during membrane peeling for VMI conditions. Differences in surgical instruments may impact these architectural alterations. PMID- 26559479 TI - In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device. AB - PURPOSE: We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. METHODS: Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. RESULTS: In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. CONCLUSIONS: Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks. PMID- 26559480 TI - Immunofluorescence Tomography of Mouse Ocular Surface Epithelial Stem Cells and Their Niche Microenvironment. AB - PURPOSE: Currently, there are no definitive immunomarkers for epithelial stem cells (corneal and conjunctival) or their poorly understood niche microenvironment. The H2B-GFP/K5tTA mouse enables visualization of label retaining cells (LRCs), which exhibit the functional marker of stem cell quiescence. We used immunofluorescence tomography to evaluate putative stem cell markers and LRCs of the mouse ocular surface. METHODS: H2B-GFP/K5tTA mice were pulsed for 56 days and then chased with doxycycline to label LRCs. Limbus and eyelid tissue was 3-dimensionally (3-D) reconstructed using immunofluorescence tomography to identify and characterize LRCs using the putative stem cell markers sox9, keratin 19, lrig1, blimp1, and abcb5. RESULTS: After 28 days of chase, LRCs were localized to the entire limbus epithelium and, infrequently, the anterior limbal stroma. Label-retaining cells comprised 3% of limbal epithelial cells after 56 days of chase. Conjunctival LRCs were localized to the fornix and comprised 4% of the total fornix epithelial cells. No stem cell immunomarker was specific for ocular surface LRCs; however, blimp1 enriched for limbal basal epithelial cells and 100% of green fluorescent protein-positive (GFP+) cells at the limbus and fornix were found to be lrig1-positive. CONCLUSIONS: Label retaining cells represent a larger population of the mouse limbus than previously thought. They decrease in number with increased doxycycline chase, suggesting that LRC populations with different cell cycle lengths exist at the limbus. We conclude that current immunomarkers are unable to colocalize with the functional marker of epithelial stem cell quiescence; however, blimp1 may enrich for limbal epithelial basal cells. PMID- 26559481 TI - The skin as an orchestrator of influenza immunity. PMID- 26559482 TI - Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single centre, double-blind, randomised, controlled phase 2b/3 trial. AB - BACKGROUND: Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group. METHODS: In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023. FINDINGS: We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain, seroconversion at day 7 occurred in 39 participants (98%) in the INF-Q-ID group, 25 (63%) in the INF-C-ID group, 18 (45%) in the INF-C-IM group, and none in the SAL-Q-ID group; for the A/Victoria/H3N2, this was 30 (75%) in the INF-Q-ID group, four (10%) in the INF-C-ID group, four (10%) in the INF-C-IM group, and none in the SAL-Q-ID group; and for the B/Massachusetts (Yamagata lineage) strain, this was 36 (90%) in the INF-Q-ID group, 27 (68%) in the INF-C-ID group, 17 (43%) in the INF-C-IM group, and one (3%) in the SAL-Q-ID group (p<0.0001 for all three vaccine strains). Adverse reactions were infrequent and self-limited and did not differ between the four groups. Furthermore, the seroconversion rate against the four non-vaccine strains was better in the INF-Q-ID group than in the control groups on days 7 and 21 (p<0.0001). The most common adverse events were grade 1 redness (five participants in the INF-Q-ID group, three in INF-C-ID, one in INF-C IM, and one in SAL-Q-ID) and grade 1 swelling (seven participants in INF-Q-ID group, five in INF-C-ID, three in INF-C-IM, and two in SAL-Q-ID. INTERPRETATION: Topical application of imiquimod before intradermal trivalent influenza vaccine significantly improved immunogenicity against the vaccine influenza strains in young healthy individuals and increased immunogenicity against the non-vaccine strains, especially the antigenically drifted H3N2 strain of 2015, which was not included in the 2013-14 recommended vaccine. Further studies should be done to establish the efficacy and safety of this approach for other injectable vaccines to augment the onset and range of protection. FUNDING: The Shaw Foundation Hong Kong, Health and Medical Research Fund (Hong Kong, China), The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR (Department of Health, Hong Kong, China), The Providence Foundation, Respiratory Viral Research Foundation. PMID- 26559483 TI - Prevalence of overweight and obesity among nurses in Scotland: A cross-sectional study using the Scottish Health Survey. AB - BACKGROUND: Increasing prevalence of overweight and obesity represents a global pandemic. As the largest occupational group in international healthcare systems nurses are at the forefront of health promotion to address this pandemic. However, nurses own health behaviours are known to influence the extent to which they engage in health promotion and the public's confidence in advice offered. Estimating the prevalence of overweight and obesity among nurses is therefore important. However, to date, prevalence estimates have been based on non representative samples and internationally no studies have compared prevalence of overweight and obesity among nurses to other healthcare professionals using representative data. OBJECTIVES: To estimate overweight and obesity prevalence among nurses in Scotland, and compare to other healthcare professionals and those working in non-heath related occupations. DESIGN: Cross-sectional study using a nationally representative sample of five aggregated annual rounds (2008-2012) of the Scottish Health Survey. SETTING: Scotland. PARTICIPANTS: 13,483 adults aged 17-65 indicating they had worked in the past 4 weeks, classified in four occupational groups: nurses (n=411), other healthcare professionals (n=320), unqualified care staff (n=685), and individuals employed in non-health related occupations (n=12,067). MAIN OUTCOME MEASURES: Prevalence of overweight and obesity defined as Body Mass Index>=25.0. METHODS: Estimates of overweight and obesity prevalence in each occupational group were calculated with 95% confidence intervals (CI). A logistic regression model was then built to compare the odds of being overweight or obese with not being overweight or obese for nurses in comparison to the other occupational categories. Data were analysed using SAS 9.1.3. RESULTS: 69.1% (95% CI 64.6, 73.6) of Scottish nurses were overweight or obese. Prevalence of overweight and obesity was higher in nurses than other healthcare professionals (51.3%, CI 45.8, 56.7), unqualified care staff (68.5%, CI 65.0, 72.0) and those in non-health related occupations (68.9%, CI 68.1, 69.7). A logistic regression model adjusted for socio-demographic composition indicated that, compared to nurses, the odds of being overweight or obese was statistically significantly lower for other healthcare professionals (Odds Ratio [OR] 0.45, CI 0.33, 0.61) and those in non-health related occupations (OR 0.78, CI 0.62, 0.97). CONCLUSIONS: Prevalence of overweight and obesity among Scottish nurses is worryingly high, and significantly higher than those in other healthcare professionals and non-health related occupations. High prevalence of overweight and obesity potentially harms nurses' own health and hampers the effectiveness of nurses' health promotion role. Interventions are therefore urgently required to address overweight and obesity among the Scottish nursing workforce. PMID- 26559484 TI - Self-reactive CD4(+) T cells activated during viral-induced demyelination do not prevent clinical recovery. AB - BACKGROUND: Microbial infections have been implicated in initiating and enhancing severity of autoimmune diseases including the demyelinating disease multiple sclerosis (MS). Nevertheless, the incidence of both acute and persisting viral infections without evidence of autoimmune sequelae suggests that this process is well controlled. The conditions promoting or stemming self-reactive (SR) T cells following viral-induced tissue damage thus need to be better defined. Using a non fatal viral mouse model of encephalomyelitis associated with demyelination and disability, yet ultimate clinical improvement, this study set out to monitor uptake and presentation of endogenous myelin antigens, as well as induction and fate of SR T cells. METHODS: Activation and central nervous system (CNS) recruitment of myelin-specific CD4 T cells was analyzed by flow cytometry during encephalomyelitis induced by a glia tropic murine coronavirus. Potential antigen presenting cells (APC) ingesting myelin were characterized by flow cytometry and their ability to activate SR T cells tested by co-culture with carboxyfluorescein succinimidyl ester (CFSE)-labeled myelin-specific CD4 T cells. Endogenous SR T cell kinetics was analyzed within both cervical lymph nodes and CNS by Enzyme Linked ImmunoSpot (ELISPOT) following viral infection. RESULTS: The data demonstrate the presence of APC capable of activating SR T cells in both draining lymph nodes and the CNS temporally correlating with overt demyelination. While both the CNS-infiltrating myeloid population and microglia ingested myelin, only CNS-infiltrating APC were capable of presenting endogenous myelin antigen to SR T cells ex vivo. Finally, SR T cell activation from the endogenous T cell repertoire was most notable when infectious virus was controlled and paralleled myelin damage. Although SR T cell accumulation peaked in the persistently infected CNS during maximal demyelination, they were not preferentially retained. Their gradual decline, despite ongoing demyelination, suggested minimal re stimulation and pathogenic function in vivo consistent with the lack of autoimmune symptoms. CONCLUSIONS: The results demonstrate the potential for CNS tissue destruction to induce and recruit SR T cells to the injury site and support a host suppressive mechanism limiting development of autoimmunity. PMID- 26559485 TI - In vitro effects of bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), or VO(dmpp)2, on insulin secretion in pancreatic islets of type 2 diabetic Goto Kakizaki rats. AB - Vanadium compounds have been explored as therapy of diabetes, and most studies have focussed on insulin mimetic effects, i.e. reducing hyperglycemia by improving glucose sensitivity and thus glucose uptake in sensitive tissues. We have recently shown that bis(1,2-dimethyl-3-hydroxy-4 pyridinonato)oxidovanadium(IV), VO(dmpp)2, has promising effects when compared to another vanadium compound, bis(maltolato)oxidovanadium(IV), BMOV, and insulin itself, in isolated adipocytes and in vivo in Goto-Kakizaki (GK) rats, an animal model of hereditary type 2 diabetes (T2D).We now have investigated in GK rats whether VO(dmpp)2 also modulates another important defect in T2D, impaired insulin secretion. VO(dmpp)2, but not BMOV, stimulated insulin secretion from isolated GK rat pancreatic islets at high, 16.7mM, but not at low-normal, 3.3 mM, glucose concentration. Mechanistic studies demonstrate that the insulin releasing effect of VO(dmpp)2 is due to its interaction with several steps in the stimulus secretion coupling for glucose, including islet glucose metabolism and K-ATP channels, L-type Ca2+ channels, modulation by protein kinases A and C, as well as the exocytotic machinery. In conclusion, VO(dmpp)2 exhibits properties of interest for treatment of the insulin secretory defect in T2D, in addition to its well-described insulin mimetic activity. PMID- 26559486 TI - Fertility desires, family planning use and pregnancy experience: longitudinal examination of urban areas in three African countries. AB - BACKGROUND: Many women have inconsistent fertility desires and contraceptive use behaviors. This increases their risk of unintended pregnancies. Inconsistencies may reflect barriers to family planning (FP) use but may also reflect ambivalence toward future childbearing. Using urban data from Kenya, Nigeria, and Senegal, this study examines the role of fertility desires and FP use behaviors on pregnancy experience over a 2-year follow-up period. METHODS: Data come from baseline and 2-year follow-up among urban women interviewed in Kenya, Nigeria, and Senegal. At baseline (2010/2011), women were asked about their future fertility desires (want child soon, want to delay >2 years, does not want) and current FP use. At midterm (2012/2013), women were asked if they were currently pregnant or had a birth in the 2-year period. We examine the association between baseline fertility desires and FP use with pregnancy experience and desirability of an experienced pregnancy. RESULTS: In the 2-year follow-up period, 27-39% of women in union experienced a pregnancy or birth. In Kenya and Nigeria, 30-35% of women using a modern FP method experienced a pregnancy/birth; the percentage with a pregnancy/birth was slightly higher among women not using at baseline (41% in both countries). In Senegal, the distinction between pregnancy experience between users and non-users was greater (16% vs. 31%, respectively). In all countries, pregnancy was less common among users of long-acting and permanent methods; only a small percentage of women use these methods. Women not wanting any(more) children were the least likely to experience a pregnancy in the 2-year follow-up period. No differences were observed between those who wanted to delay and those who wanted soon. Multivariate findings demonstrate distinctions in pregnancy experience by fertility desires among modern FP users. Non-users have similar pregnancy experience by fertility desires. CONCLUSIONS: Fertility desires are not stable; providers need to consider the fluidity of fertility desires in counseling clients. Programs focusing on new FP users may miss women who are the most motivated to avoid a pregnancy and need to switch to a more effective method; this will result in less unintended pregnancies overall. PMID- 26559487 TI - The British Society for Rheumatology Biologics Registers in Ankylosing Spondylitis (BSRBR-AS) study: Protocol for a prospective cohort study of the long term safety and quality of life outcomes of biologic treatment. AB - BACKGROUND: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials. METHODS/DESIGN: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naive to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis. DISCUSSION: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes. CLINICAL TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was not required or obtained. PMID- 26559488 TI - Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation. AB - IMPORTANCE: While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). OBJECTIVE: To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. MAIN OUTCOME AND MEASURES: The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. RESULTS: A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22). CONCLUSIONS AND RELEVANCE: Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease. PMID- 26559489 TI - Generation of enterocyte-like cells from human induced pluripotent stem cells for drug absorption and metabolism studies in human small intestine. AB - Enterocytes play an important role in drug absorption and metabolism. However, a widely used enterocyte model, Caco-2 cell, has difficulty in evaluating both drug absorption and metabolism because the expression levels of some drug absorption and metabolism-related genes in these cells differ largely from those of human enterocytes. Therefore, we decided to generate the enterocyte-like cells from human induced pluripotent stem (iPS) cells (hiPS-ELCs), which are applicable to drug absorption and metabolism studies. The efficiency of enterocyte differentiation from human iPS cells was significantly improved by using EGF, SB431542, and Wnt3A, and extending the differentiation period. The gene expression levels of cytochrome P450 3A4 (CYP3A4) and peptide transporter 1 in the hiPS-ELCs were higher than those in Caco-2 cells. In addition, CYP3A4 expression in the hiPS-ELCs was induced by treatment with 1, 25-dihydroxyvitamin D3 or rifampicin, which are known to induce CYP3A4 expression, indicating that the hiPS-ELCs have CYP3A4 induction potency. Moreover, the transendothelial electrical resistance (TEER) value of the hiPS-ELC monolayer was approximately 240 Omega*cm(2), suggesting that the hiPS-ELC monolayer could form a barrier. In conclusion, we succeeded in establishing an enterocyte model from human iPS cells which have potential to be applied for drug absorption and metabolism studies. PMID- 26559490 TI - Inbreeding and purging at the genomic Level: the Chillingham cattle reveal extensive, non-random SNP heterozygosity. AB - Local breeds of livestock are of conservation significance as components of global biodiversity and as reservoirs of genetic variation relevant to the future sustainability of agriculture. One such rare historic breed, the Chillingham cattle of northern England, has a 350-year history of isolation and inbreeding yet shows no diminution of viability or fertility. The Chillingham cattle have not been subjected to selective breeding. It has been suggested previously that the herd has minimal genetic variation. In this study, high-density SNP genotyping with the 777K SNP chip showed that 9.1% of loci on the chip are polymorphic in the herd, compared with 62-90% seen in commercial cattle breeds. Instead of being homogeneously distributed along the genome, these loci are clustered at specific chromosomal locations. A high proportion of the Chillingham individuals examined were heterozygous at many of these polymorphic loci, suggesting that some loci are under balancing selection. Some of these frequently heterozygous loci have been implicated as sites of recessive lethal mutations in cattle. Linkage disequilibrium equal or close to 100% was found to span up to 1350 kb, and LD was above r(2) = 0.25 up to more than 5000 kb. This strong LD is consistent with the lack of polymorphic loci in the herd. The heterozygous regions in the Chillingham cattle may be the locations of genes relevant to fitness or survival, which may help elucidate the biology of local adaptation in traditional breeds and facilitate selection for such traits in commercial cattle. PMID- 26559491 TI - Financial team incentives improved recording of diagnoses in primary care: a quasi-experimental longitudinal follow-up study with controls. AB - BACKGROUND: In primary care, financial incentives have usually been directed to physicians because they are thought to make the key decisions in order to change the functions of a medical organization. There are no studies regarding the impact that directing these incentives to all disciplines of the care team (e.g. group bonuses for both nurses and doctors) may have, despite the low frequency with which diagnoses were being recorded for primary care visits to doctors. This study tested the effect of offering group bonuses to the care teams. METHODS: This was a retrospective quasi-experimental study with before-and-after settings and two control groups. In the intervention group, the mean percentage of visits to a doctor for which a diagnosis was recorded by each individual care team (mean team-based percentage of monthly visits to a doctor with recorded diagnoses) and simultaneously the same data was gathered from two different primary care settings where no team bonuses were applied. To study the sustainability of changes obtained with the group bonuses the respective data were derived from the electronic health record system for 2 years after the cessation of the intervention. The differences in the rate of marking diagnoses was analyzed with ANOVA and RM-ANOVA with appropriate post hoc tests, and the differences in the rate of change in marking diagnoses was analyzed with linear regression followed by t-test. RESULTS: The proportion of doctor visits having recorded diagnoses in the teams was about 55 % before starting to use group bonuses and 90 % after this intervention. There was no such increase in control units. The effect of the intervention weakened slightly after cessation of the group bonuses. CONCLUSION: Group bonuses may provide a method to alter clinical practices in primary care. However, sustainability of these interventions may diminish after ceasing this type of financial incentive. PMID- 26559492 TI - Saccharibacillus deserti sp. nov., isolated from desert soil. AB - A Gram-stain-positive, facultatively anaerobic bacterial strain, designated WLJ055T, with polar and subpolar flagella was isolated from the top layer of desert soil from Erdos, Inner Mongolia, northern China. Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that strain WLJ055T was a member of the genus Saccharibacillus, and shared 97.17-97.24 % 16S rRNA gene sequence similarities with Saccharibacillus sacchari GR21T and Saccharibacillus kuerlensis HR1T. The major polar lipids of strain WLJ055T were diphosphatidylglycerol, phosphatidylglycerol, an unknown aminophospholipid, two unknown glycolipids and an unknown phosphoglycolipid. MK-7 was the predominant menaquinone, while anteiso C15 : 0, C16 : 0, iso-C16 : 0, and anteiso-C17 : 0 were the major cellular fatty acids. Its genomic DNA G+C content was 55.5 mol%. DNA-DNA hybridization revealed that strain WLJ055T showed 45 +/- 5 % and 40 +/- 5 % genomic DNA relatedness with its two closest relatives, S. sacchari GR21T and S. kuerlensis HR1T, respectively. The results of physiological and biochemical tests allowed the discrimination of strain WLJ055T from its phylogenetic relatives. Saccharibacillus deserti sp. nov. is therefore proposed to be a novel species of the genus Saccharibacillus, with strain WLJ055T ( = CGMCC 1.15276T = KCTC 33693T) as the type strain. PMID- 26559493 TI - The growth of a skin emergency teledermatology service from 2008 to 2014. AB - OBJECTIVE: To conduct an audit of the Skin Emergency Telemedicine Service at Princess Alexandra Hospital in Brisbane from January to December 2014, and determine whether there has been any change in the number, type and location of referrals. METHODS: Retrospective analyses of referrals to the teledermatology service were conducted and compared with the 2012 audit. Main outcomes assessed included the number of referrals, referral site location, telediagnosis categories, image characteristics and response times. RESULTS: In 2014, 318 cases were referred to the teledermatology service. The highest number of cases (n = 140) were referred from Princess Alexandra Hospital and Queen Elizabeth II Jubilee Hospital emergency departments. However, referrals to the teledermatology service came from as far as 1600 km distant from Brisbane. The most common provisional telediagnoses were dermatitis or eczema, skin infection or drug eruption. Over half of all referrals (62%) received a response within 3 h and a further 20% were responded to within 3-6 h. Almost half all referring doctors (48%) attached very large image files (> 500 kb) to their referral. CONCLUSIONS: The Skin Emergency Telemedicine Service has proved to be a successful, sustainable and valuable addition to the specialist dermatology services provided across Queensland. With adequate funding and resources and appropriate attention to ethical and legal considerations, our service could significantly change the management of Queenslanders with acute skin conditions. PMID- 26559494 TI - Parents' perception of their child's weight status and intention to intervene: a Western Australian cross-sectional population survey, 2009-12. AB - OBJECTIVE: To report on parents' perceptions of their child's weight status and how the child's body mass index (BMI) is associated with parent intentions to change or maintain the child's weight. METHODS: Estimates were derived via data collected from 4,437 parents from 2009 to 2012 as part of the Western Australian Health and Wellbeing Surveillance System. To measure weight perceptions, parents were asked, "Is your child underweight, normal weight, overweight or very overweight?" BMI values were also derived via parent-reported height and weight. Parent intentions were assessed by asking parents, "What are your intentions regarding your child's weight?" RESULTS: Significantly fewer parents perceived their child as overweight (8.2%) or very overweight (0.2%) than was derived via parent-reported height and weight (16.3% and 5.8%, respectively). More than half the parents with children above or below the healthy BMI range reported an intention to "do nothing" about their child's weight (between 54.5% and 70.0%). CONCLUSIONS: A large proportion of Western Australian parents misjudge their child's weight status and the majority express no intention to help their child achieve a healthy weight. IMPLICATIONS: The results reinforce the importance of population-level, parent-focussed interventions targeting perceptions of children's weight and appropriate action. PMID- 26559495 TI - A benign juvenile environment reduces the strength of antagonistic pleiotropy and genetic variation in the rate of senescence. AB - The environment can play an important role in the evolution of senescence because the optimal allocation between somatic maintenance and reproduction depends on external factors influencing life expectancy. The aims of this study were to experimentally test whether environmental conditions during early life can shape senescence schedules, and if so, to examine whether variation among individuals or genotypes with respect to the degree of ageing differs across environments. We tested life-history plasticity and quantified genetic effects on the pattern of senescence across different environments within a reaction norm framework by using an experiment on the three-spined stickleback (Gasterosteus aculeatus, Linnaeus) in which F1 families originating from a wild annual population experienced different temperature regimes. Male sticklebacks that had experienced a more benign environment earlier in life subsequently reduced their investment in carotenoid-based sexual signals early in the breeding season, and consequently senesced at a slower rate later in the season, compared to those that had developed under harsher conditions. This plasticity of ageing was genetically determined. Both antagonistic pleiotropy and genetic variation in the rate of senescence were evident only in the individuals raised in the harsher environment. The experimental demonstration of genotype-by-environment interactions influencing the rate of reproductive senescence provides interesting insights into the role of the environment in the evolution of life histories. The results suggest that benign conditions weaken the scope for senescence to evolve and that the dependence on the environment may maintain genetic variation under selection. PMID- 26559496 TI - Time to talk about work-hour impact on anesthesiologists: The effects of sleep deprivation on Profile of Mood States and cognitive tasks. AB - BACKGROUND: A physician's fatigue raises significant concerns regarding personal and patient safety. Effects of sleep deprivation on clinical performance and the quality of patient care are major considerations of today's health care environment. AIM: To evaluate the impact of partial sleep deprivation after a 17 h overnight call (3 pm-7 am) on the mood status and cognitive skills of anesthesiologists in an academic clinical hospital setting, as compared to these parameters during regular working hours. METHODS: Taking circadian rhythm into account, the following measures were assessed in 21 pediatric anesthesiologists at two time points over the course of the study; (i) between 7 and 8 am on a regular non call day, and (ii) between 7 and 8 am after a 17-h in-house call (3 pm-7 am). Six mood states were assessed using the Profile of Mood States. A Total Mood Disturbance (TMD) score was obtained as the sum of all mood scores minus vigor. The total score provides a global estimate of affective state. Simple cognitive tests were similarly administered to assess cognitive skills. A two tailed paired t-test was used to compare data between regular and post call days. A P < 0.05 was used. RESULTS: The study cohort included 21 pediatric anesthesiologists at a tertiary care children's hospital. Tension, anger, fatigue, confusion, TMD, irritability, feeling jittery, and sleepiness were significantly affected (P < 0.05). A decrease in vigor, energy, and confidence was observed after a night call shift (P < 0.05). There was also a decrease in being "talkative" after the call shift (P < 0.05). CONCLUSION: Partial sleep deprivation affects the total mood status of anesthesiologists and impacts their cognitive skills. These findings are particularly relevant in a context of increased work expectation, particularly on clinical performance in our modern medical system. Such observations suggest that there may be changes that impact the safety of our patients and the quality of health care that is provided. PMID- 26559497 TI - In vitro model for gastroduodenal reflux-induced nuclear factor-kappaB activation and its role in hypopharyngeal carcinogenesis. AB - BACKGROUND: The purpose of this study was to investigate whether gastroduodenal reflux can play a role in the pathogenesis of hypopharyngeal cancer; therefore, we assessed its effect on the nuclear factor-kappa B (NF-kappaB) pathway, as similarly noted in the esophagus. METHODS: We exposed human cells derived from the hypopharyngeal epithelium to bile acids or deoxycholic acid. We centered our study on the transcriptional activation of NF-kappaB pathway, previously linked to head and neck squamous cell carcinoma (HNSCC). RESULTS: We show that acidic bile salts induce: (1) NF-kappaB activation with high cytoplasmic Bcl-2 expression; (2) significant increase in expression v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA(p65)), v-rel avian reticuloendotheliosis viral oncogene homolog (c-REL) signal transducer and activator of transcription 3 (STAT3), isoform of transformation related protein p63 (DeltaNp63), B-cell lymphoma 2 (Bcl-2), tumor necrosis factor alpha (TNF alpha), epidermal growth factor receptor (EGFR), and wingless type MMTV integration site family member 5A (WNT5A) and a decrease in tumor protein p53 (Tp53); and (3) phenotypic changes that are similar to the phenotype of the untreated hypopharyngeal cancer cell line, University of Michigan squamous cell carcinoma (UMSCC)-11B. These changes are not seen when cells were exposed to neutral control or acid alone. CONCLUSION: Our findings in vitro are consistent with the hypothesis that gastroduodenal reflux plays a role in hypopharyngeal carcinogenesis and its effect is mediated through activation of NF-kappaB pathway. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1381-E1391, 2016. PMID- 26559498 TI - Relation of Elite Rifle Shooters' Technique-Test Measures to Competition Performance. AB - PURPOSE: To describe the long-term changes in shooting technique in relation to competition performances in elite air-rifle shooters. METHODS: Seventeen elite shooters completed simulated air-rifle shooting-competition series in 3 consecutive seasons, participating on 15 +/- 7 testing occasions. Shooting score and aiming-point-trajectory variables were obtained with an optoelectronic shooting device, and postural-balance variables were measured with force platform. Shooters' competition results were collected from all international and national competitions during the 3-y period. RESULTS: Mean test score, stability of hold, aiming accuracy, cleanness of triggering, and postural balance improved during the 3-y period (ANOVA, time, P < .05-.01). Seasonal mean test results in stability of hold (R = -.70, P = .000) and cleanness of triggering (R = -.75, P = .000) were related to competition performances. Changes in stability of hold (R = -.61, P = .000) and cleanness of triggering (R = -.39, P = .022) were also related to the changes in competition performances. Postural balance in shooting direction was more related to cleanness of triggering (R = .57, P = .000), whereas balance in cross-shooting direction was more related to stability of hold (R = .70, P = .000). CONCLUSIONS: The shooting-technique testing used in the current study seems to be a valid and useful tool for long-term performance assessment. Stability of hold, cleanness of triggering, and postural balance can be further developed even at the elite level, resulting in improved competition performances. PMID- 26559499 TI - Use of a porcine urinary bladder acellular matrix for corneal reconstruction in dogs and cats. AB - OBJECTIVE: To describe the use of a porcine urinary bladder acellular matrix for surgical reconstruction of the cornea in cases of canine and feline deep corneal ulcers, and feline corneal sequestra. MATERIALS AND METHODS: Twenty-seven dogs and three cats with deep corneal ulcers and seven cats with corneal sequestra were included in the study with overall 38 eyes. For each patient, the necrotic material (ie corneal sequestrum or collagenolytic tissue) was removed by circular lamellar keratectomy. The collagen graft was then cut and prepared to match the stromal defect and then sutured into the lamellar keratectomy bed using interrupted and continuous patterns of absorbable polyglactin 9-0 sutures. Postoperative medical treatment consisted of topical and systemic administration of antibiotics, combined with topical administration of atropine sulfate. The animals were examined 18, 45, and 90 days after the surgery. RESULTS: Postoperative examination revealed complete integration of the biomaterial in 93.5% of ulceration cases in both species and in 100% of feline corneal sequestrum cases. In two cases of ulceration (1 dog and 1 cat), progression of the collagenolytic process at the graft periphery required an additional conjunctival graft 7 days after the first surgery. At 90 days post-op, 100% of the eyes were sighted. CONCLUSION: Use of a porcine urinary bladder acellular matrix appears to be effective in the surgical management of deep corneal ulcers and feline corneal sequestra. PMID- 26559500 TI - Influence of Solvent-Like Sidechains on the Adsorption of Light Hydrocarbons in Metal-Organic Frameworks. AB - A variety of strategies have been developed to adsorb and separate light hydrocarbons in metal-organic frameworks. Here, we present a new approach in which the pores of a framework are lined with four different C3 sidechains that feature various degrees of branching and saturation. These pendant groups, which essentially mimic a low-density solvent with restricted degrees of freedom, offer tunable control of dispersive host-guest interactions. The performance of a series of frameworks of the type Zn2 (fu-bdc)2 (dabco) (fu-bdc(2-) =functionalized 1,4-benzenedicarboxylate; dabco=1,4-diazabicyclo[2.2.2]octane), which feature a pillared layer structure, were investigated for the adsorption and separation of methane, ethane, ethylene, and acetylene. The four frameworks exhibit low methane uptake, whereas C2 hydrocarbon uptake is substantially higher as a result of the enhanced interaction of these molecules with the ligand sidechains. Most significantly, the adsorption quantities and selectivity were found to depend strongly upon the type of sidechains attached to the framework scaffold. PMID- 26559501 TI - Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC). AB - INTRODUCTION: Previous studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN. AIM: The aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes. METHODS: We conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures. MAIN OUTCOME MEASURES: The main CAN measure from EDIC follow-up year 17 was a standardized composite of R-R variation with paced breathing < 15, or R-R variation 15-20 combined with either a Valsalva ratio <= 1.5 or a decrease in diastolic blood pressure > 10 mm Hg upon standing. Continuous R-R variation and Valsalva ratio were secondary outcomes. RESULTS: Lower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia. CONCLUSIONS: Testosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known. PMID- 26559502 TI - The Anthropoid Crista Trochanterica and the Hip Joint Capsule. AB - The tubercle on the posterior aspect of the femoral neck (the crista trochanterica) has been repeatedly remarked upon because of its presence in early fossil apes, yet the function of this tubercle has eluded researchers. The prevailing explanation for the tubercle is that it relates to a strong ischiofemoral ligament, although none of the hypotheses for this bony projection have been systematically evaluated. This study surveyed 41 extant anthropoid species (n = 267 individuals) for the presence of a crista trochanterica. The soft tissue structures of the hip joint were then dissected and described for a sample of anthropoid cadavers (n = 14) in order to evaluate different hypotheses related to function of this tubercle. This study confirmed that the crista trochanterica is found in most cercopithecoids and platyrrhines, and is not present in great apes. The tubercle is rarely present in hylobatids, contrary to prior reports. The ischiofemoral ligament is not usually well-developed in anthropoids and does not fully explain the crista trochanterica morphology, although all cadavers displayed a well-developed zona orbicularis running along the posterior aspect of the joint capsule. The hip joint capsule itself inserted along the crista trochanterica in some individuals, typically those with an elongate crista trochanterica, but was highly variable in regards to the position of the tubercle. The hypotheses for the crista trochanterica are considered within the context of these findings, although the exact function of the tubercle remains unresolved. PMID- 26559504 TI - Current-induced forces: a new mechanism to induce negative differential resistance and current-switching effect in molecular junctions. AB - Current-induced forces can excite molecules, polymers and other low-dimensional materials, which in turn leads to an effective gate voltage through Holstein interaction. Here, by taking a short asymmetric DNA junction as an example, and using the Langevin approach, we find that when suppression of charge transport by the effective gate voltage surpasses the current increase from an elevated voltage bias, the current-voltage (I-V) curves display strong negative differential resistance (NDR) and perfect current-switching characteristics. The asymmetric DNA chain differs in mechanical stability under inverse voltages and the I-V curve is asymmetric about inverse biases, which can be used to understand recent transport experiments on DNA chains, and meanwhile provides a new strategy to realize NDR in molecular junctions and other low-dimensional quantum systems. PMID- 26559503 TI - Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet? AB - The optimal choice of cancer therapy depends upon analysis of the tumor genome for druggable molecular alterations. The spatial and temporal intratumor heterogeneity of cancers creates substantial challenges, as molecular profile depends on time and site of tumor tissue collection. To capture the entire molecular profile, multiple biopsies from primary and metastatic sites at different time points would be required, which is not feasible for ethical or economic reasons. Molecular analysis of circulating cell-free DNA offers a novel, minimally invasive method that can be performed at multiple time-points and plausibly better represents the prevailing molecular profile of the cancer. Molecular analysis of this cell-free DNA offers multiple clinically useful applications, such as identification of molecular targets for cancer therapy, monitoring of tumor molecular profile in real time, detection of emerging molecular aberrations associated with resistance to particular therapy, determination of cancer prognosis and diagnosis of cancer recurrence or progression. PMID- 26559505 TI - Identification of differentially methylated loci using wavelet-based functional mixed models. AB - MOTIVATION: DNA methylation is a key epigenetic modification that can modulate gene expression. Over the past decade, a lot of studies have focused on profiling DNA methylation and investigating its alterations in complex diseases such as cancer. While early studies were mostly restricted to CpG islands or promoter regions, recent findings indicate that many of important DNA methylation changes can occur in other regions and DNA methylation needs to be examined on a genome wide scale. In this article, we apply the wavelet-based functional mixed model methodology to analyze the high-throughput methylation data for identifying differentially methylated loci across the genome. Contrary to many commonly-used methods that model probes independently, this framework accommodates spatial correlations across the genome through basis function modeling as well as correlations between samples through functional random effects, which allows it to be applied to many different settings and potentially leads to more power in detection of differential methylation. RESULTS: We applied this framework to three different high-dimensional methylation data sets (CpG Shore data, THREE data and NIH Roadmap Epigenomics data), studied previously in other works. A simulation study based on CpG Shore data suggested that in terms of detection of differentially methylated loci, this modeling approach using wavelets outperforms analogous approaches modeling the loci as independent. For the THREE data, the method suggests newly detected regions of differential methylation, which were not reported in the original study. AVAILABILITY AND IMPLEMENTATION: Automated software called WFMM is available at https://biostatistics.mdanderson.org/SoftwareDownload CpG Shore data is available at http://rafalab.dfci.harvard.edu NIH Roadmap Epigenomics data is available at http://compbio.mit.edu/roadmap SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: jefmorris@mdanderson.org. PMID- 26559506 TI - WormExp: a web-based application for a Caenorhabditis elegans-specific gene expression enrichment analysis. AB - MOTIVATION: A particular challenge of the current omics age is to make sense of the inferred differential expression of genes and proteins. The most common approach is to perform a gene ontology (GO) enrichment analysis, thereby relying on a database that has been extracted from a variety of organisms and that can therefore only yield reliable information on evolutionary conserved functions. RESULTS: We here present a web-based application for a taxon-specific gene set exploration and enrichment analysis, which is expected to yield novel functional insights into newly determined gene sets. The approach is based on the complete collection of curated high-throughput gene expression data sets for the model nematode Caenorhabditis elegans, including 1786 gene sets from more than 350 studies. AVAILABILITY AND IMPLEMENTATION: WormExp is available at http://wormexp.zoologie.uni-kiel.de CONTACTS: hschulenburg@zoologie.uni-kiel.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26559507 TI - BRAKER1: Unsupervised RNA-Seq-Based Genome Annotation with GeneMark-ET and AUGUSTUS. AB - MOTIVATION: Gene finding in eukaryotic genomes is notoriously difficult to automate. The task is to design a work flow with a minimal set of tools that would reach state-of-the-art performance across a wide range of species. GeneMark ET is a gene prediction tool that incorporates RNA-Seq data into unsupervised training and subsequently generates ab initio gene predictions. AUGUSTUS is a gene finder that usually requires supervised training and uses information from RNA-Seq reads in the prediction step. Complementary strengths of GeneMark-ET and AUGUSTUS provided motivation for designing a new combined tool for automatic gene prediction. RESULTS: We present BRAKER1, a pipeline for unsupervised RNA-Seq based genome annotation that combines the advantages of GeneMark-ET and AUGUSTUS. As input, BRAKER1 requires a genome assembly file and a file in bam-format with spliced alignments of RNA-Seq reads to the genome. First, GeneMark-ET performs iterative training and generates initial gene structures. Second, AUGUSTUS uses predicted genes for training and then integrates RNA-Seq read information into final gene predictions. In our experiments, we observed that BRAKER1 was more accurate than MAKER2 when it is using RNA-Seq as sole source for training and prediction. BRAKER1 does not require pre-trained parameters or a separate expert prepared training step. AVAILABILITY AND IMPLEMENTATION: BRAKER1 is available for download at http://bioinf.uni-greifswald.de/bioinf/braker/ and http://exon.gatech.edu/GeneMark/ CONTACT: katharina.hoff@uni-greifswald.de or borodovsky@gatech.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26559508 TI - Annotation of rule-based models with formal semantics to enable creation, analysis, reuse and visualization. AB - MOTIVATION: Biological systems are complex and challenging to model and therefore model reuse is highly desirable. To promote model reuse, models should include both information about the specifics of simulations and the underlying biology in the form of metadata. The availability of computationally tractable metadata is especially important for the effective automated interpretation and processing of models. Metadata are typically represented as machine-readable annotations which enhance programmatic access to information about models. Rule-based languages have emerged as a modelling framework to represent the complexity of biological systems. Annotation approaches have been widely used for reaction-based formalisms such as SBML. However, rule-based languages still lack a rich annotation framework to add semantic information, such as machine-readable descriptions, to the components of a model. RESULTS: We present an annotation framework and guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages. We adapt widely adopted annotation approaches to rule-based models. We initially propose a syntax to store machine readable annotations and describe a mapping between rule-based modelling entities, such as agents and rules, and their annotations. We then describe an ontology to both annotate these models and capture the information contained therein, and demonstrate annotating these models using examples. Finally, we present a proof of concept tool for extracting annotations from a model that can be queried and analyzed in a uniform way. The uniform representation of the annotations can be used to facilitate the creation, analysis, reuse and visualization of rule-based models. Although examples are given, using specific implementations the proposed techniques can be applied to rule-based models in general. AVAILABILITY AND IMPLEMENTATION: The annotation ontology for rule-based models can be found at http://purl.org/rbm/rbmo The krdf tool and associated executable examples are available at http://purl.org/rbm/rbmo/krdf CONTACT: anil.wipat@newcastle.ac.uk or vdanos@inf.ed.ac.uk. PMID- 26559509 TI - Mapping of the Retrotransposable Elements Rex1 and Rex3 in Chromosomes of Eigenmannia (Teleostei, Gymnotiformes, Sternopygidae). AB - Transposable elements constitute a remarkable fraction of the eukaryote genome and show particular capacity to move and insert in specific regions of the genome. This study identified the retrotransposable elements Rex1 and Rex3 in the genomes of 6 cytotypes of Eigenmannia. The sequences were isolated by PCR, sequenced and physically mapped in the chromosomes of these cytotypes, aiming to investigate the organization and distribution of these elements in this fish group, mainly in the sex chromosomes. The FISH physical mapping revealed that both Rex1 and Rex3 elements are dispersed in small clusters throughout the chromosomes of all cytotypes analyzed. However, conspicuous blocks occur in several samples, including an accentuated accumulation of the Rex3 element in X(1) and X(2) chromosomes of Eigenmannia sp. 2 and in the X chromosome of E. virescens. The accumulations are coincident with heterochromatin-rich regions, suggesting that Rex3 played a role in the differentiation process of the sex chromosomes. PMID- 26559511 TI - Environmental risk factors associated with bovine tuberculosis among cattle in high-risk areas. AB - Our research shows that environmental features are important predictors of bovine tuberculosis (bTB) in British cattle herds in high-prevalence regions. Data from 503 case and 808 control farms included in the randomized badger culling trial (RBCT) were analysed. bTB risk increased in larger herds and on farms with greater areas of maize, deciduous woodland and marsh, whereas a higher percentage of boundaries composed of hedgerows decreased the risk. The model was tested on another case-control study outside RBCT areas, and here it had a much smaller predictive power. This suggests that different infection dynamics operate outside high-risk areas, although it is possible that unknown confounding factors may also have played a role. PMID- 26559510 TI - Tissue-specific transcriptomics and proteomics of a filarial nematode and its Wolbachia endosymbiont. AB - BACKGROUND: Filarial nematodes cause debilitating human diseases. While treatable, recent evidence suggests drug resistance is developing, necessitating the development of novel targets and new treatment options. Although transcriptomic and proteomic studies around the nematode life cycle have greatly enhanced our knowledge, whole organism approaches have not provided spatial resolution of gene expression, which can be gained by examining individual tissues. Generally, due to their small size, tissue dissection of human-infecting filarial nematodes remains extremely challenging. However, canine heartworm disease is caused by a closely related and much larger filarial nematode, Dirofilaria immitis. As with many other filarial nematodes, D. immitis contains Wolbachia, an obligate bacterial endosymbiont present in the hypodermis and developing oocytes within the uterus. Here, we describe the first concurrent tissue-specific transcriptomic and proteomic profiling of a filarial nematode (D. immitis) and its Wolbachia (wDi) in order to better understand tissue functions and identify tissue-specific antigens that may be used for the development of new diagnostic and therapeutic tools. METHODS: Adult D. immitis worms were dissected into female body wall (FBW), female uterus (FU), female intestine (FI), female head (FH), male body wall (MBW), male testis (MT), male intestine (MI), male head (MH) and 10.1186/s12864-015-2083-2 male spicule (MS) and used to prepare transcriptomic and proteomic libraries. RESULTS: Transcriptomic and proteomic analysis of several D. immitis tissues identified many biological functions enriched within certain tissues. Hierarchical clustering of the D. immitis tissue transcriptomes, along with the recently published whole-worm adult male and female D. immitis transcriptomes, revealed that the whole-worm transcriptome is typically dominated by transcripts originating from reproductive tissue. The uterus appeared to have the most variable transcriptome, possibly due to age. Although many functions are shared between the reproductive tissues, the most significant differences in gene expression were observed between the uterus and testis. Interestingly, wDi gene expression in the male and female body wall is fairly similar, yet slightly different to that of Wolbachia gene expression in the uterus. Proteomic methods verified 32 % of the predicted D. immitis proteome, including over 700 hypothetical proteins of D. immitis. Of note, hypothetical proteins were among some of the most abundant Wolbachia proteins identified, which may fulfill some important yet still uncharacterized biological function. CONCLUSIONS: The spatial resolution gained from this parallel transcriptomic and proteomic analysis adds to our understanding of filarial biology and serves as a resource with which to develop future therapeutic strategies against filarial nematodes and their Wolbachia endosymbionts. PMID- 26559512 TI - Bayesian hierarchical models suggest oldest known plant-visiting bat was omnivorous. AB - The earliest record of plant visiting in bats dates to the Middle Miocene of La Venta, the world's most diverse tropical palaeocommunity. Palynephyllum antimaster is known from molars that indicate nectarivory. Skull length, an important indicator of key traits such as body size, bite force and trophic specialization, remains unknown. We developed Bayesian models to infer skull length based on dental measurements. These models account for variation within and between species, variation between clades, and phylogenetic error structure. Models relating skull length to trophic level for nectarivorous bats were then used to infer the diet of the fossil. The skull length estimate for Palynephyllum places it among the larger lonchophylline bats. The inferred diet suggests Palynephyllum fed on nectar and insects, similar to its living relatives. Omnivory has persisted since the mid-Miocene. This is the first study to corroborate with fossil data that highly specialized nectarivory in bats requires an omnivorous transition. PMID- 26559513 TI - Transfer of humoural immunity over two generations in urban pigeons. AB - Maternal antibodies (MatAb) are known to provide passive protection early in life for young vertebrates but their effects on the development of offspring immune response across generations are still unknown. Here, we investigated the effects of antigen exposure (keyhole limpet haemocyanin, KLH) experienced by urban pigeon (Columba livia) females on the amount of antigen-specific antibodies (Abs) transferred into the egg yolk of their daughters and on the humoural immune response towards this same antigen in their grandchildren. We found that chicks from KLH-injected maternal grandmothers had a higher humoural response than chicks from sham-injected grandmothers. However, we did not detect a significant effect of female KLH exposure on the ability of their daughters to transmit anti KLH Abs into their eggs. These results suggest that antigen exposure at one generation may shape the immune profile of offspring over two next generations, although the underlying mechanisms remain to be investigated. PMID- 26559514 TI - Electric shock causes physiological stress responses in shore crabs, consistent with prediction of pain. AB - Animal pain is defined by a series of expectations or criteria, one of which is that there should be a physiological stress response associated with noxious stimuli. While crustacean stress responses have been demonstrated they are typically preceded by escape behaviour and thus the physiological change might be attributed to the behaviour rather than a pain experience. We found higher levels of stress as measured by lactate in shore crabs exposed to brief electric shock than non-shocked controls. However, shocked crabs showed more vigorous behaviour than controls. We then matched crabs with the same level of behaviour and still found that shocked crabs had stronger stress response compared with controls. The finding of the stress response, coupled with previous findings of long-term motivational change and avoidance learning, fulfils the criteria expected of a pain experience. PMID- 26559515 TI - Social organization in Eulipotyphla: evidence for a social shrew. AB - Shrews and their close relatives (order Eulipotyphla) are typically considered to be solitary. This impacts our understanding of mammalian social evolution: (i) the ancestor of mammals is believed to have been shrew-like, and even though Eulipotyphla are not more basal than other mammalian orders, this might have been one reason why the first mammals have been assumed to be solitary-living; (ii) Eulipotyphla are the third largest mammalian order, with hundreds of species entering comparative analyses. We review primary field studies reporting the social organization of Eulipotyphla, doing a literature research on 445 species. Primary literature was only available for 16 of the 445 species. We found 56% of the studied species to be social (38% were living in pairs), which is in sharp contrast to the 0.5 and 8% reported in other databases. We conclude that the available information indicates that shrews are more sociable than generally believed. An interesting alternative hypothesis is that the mammalian ancestor might have been pair-living. To understand the social evolution of mammals, comparative studies must be based on reliable and specific information, and more species of all orders must be studied in the field. PMID- 26559516 TI - Teaching examples for the design of experiments: geographical sensitivity and the self-fulfilling prophecy. AB - Many scientists believe that small experiments, guided by scientific intuition, are simpler and more efficient than design of experiments. This belief is strong and persists even in the face of data demonstrating that it is clearly wrong. In this paper, we present two powerful teaching examples illustrating the dangers of small experiments guided by scientific intuition. We describe two, simple, two dimensional spaces. These two spaces give rise to, and at the same time appear to generate supporting data for, scientific intuitions that are deeply flawed or wholly incorrect. We find these spaces useful in unfreezing scientific thinking and challenging the misplaced confidence in scientific intuition. PMID- 26559517 TI - Profunda artery perforator flap for perineal reconstruction: A new indication. PMID- 26559518 TI - Communicating information to the general practitioner: the example of vemurafenib for metastatic melanoma. PMID- 26559519 TI - Oromucosal film preparations: points to consider for patient centricity and manufacturing processes. AB - INTRODUCTION: According to the European Pharmacopoeia, oromucosal films comprise mucoadhesive buccal films and orodispersible films. Both oral dosage forms receive considerable interest in the recent years as commercially available pharmaceutical products and as small scale personalized extemporaneous preparations. AREAS COVERED: In this review, technological issues such as viscosity of the casting liquid, mechanical properties of the film, upscaling and the stability of the casting solution and produced films will be discussed. Furthermore, patient-related problems like appearance, mucosal irritation, taste, drug load, safety and biopharmaceutics are described. Current knowledge and directions for solutions are summarized. EXPERT OPINION: The viscosity of the casting solution is a key factor for producing suitable films. This parameter is amongst others dependent on the polymer and active pharmaceutical ingredient, and the further excipients that are used. For optimal patient compliance, an acceptable taste and palatability are desirable. Safe and inert excipients should be used and appropriate packaging should be provided to produced films. Absorption through the oral mucosa will vary for each active compound, formulation and patient, which gives rise to pharmacokinetic questions. Finally, the European Pharmacopoeia needs to specify methods, requirement and definitions for oromucosal film preparations based on bio-relevant data. PMID- 26559520 TI - Electronic enhancements to blood ordering reduce component waste. AB - BACKGROUND: The effect on component wastage after enhancing the clinician's ability to order blood products in the computerized physician order entry (CPOE) system was investigated in a multihospital network. METHODS: A novel field was added to the CPOE of eight hospitals within a health care system allowing the physician to reserve a red blood cell (RBC) unit for transfusion at a later time. Simultaneously, an electronic means of communication with the blood bank was implemented requiring the nurse to ensure that the patient was prepared for the transfusion before a product could be issued. The wastage rates in the 12 months after these electronic enhancements (Phase 2) was compared to the preceding 19 months of a non-CPOE-based waste reduction campaign (Phase 1) and to the 24 months before the campaign (baseline period). RESULTS: There were significant reductions in platelet (PLT) waste between the baseline period and Phase 1 (p < 0.05) and between Phase 2 and both Phase 1 and the baseline period (p < 0.05). The annual systemwide cost savings in wasted PLTs between the baseline period and Phase 2 was approximately $123,300. RBC waste was significantly reduced between Phase 2 and both Phase 1 and the baseline period (p < 0.05). Cryoprecipitate waste was reduced between Phase 2 and the baseline period (p < 0.05), while plasma waste did not change between the three periods. CONCLUSIONS: Implementing a multifaceted approach to waste reduction led to a significant reduction in wastage for RBCs, PLTs, and cryoprecipitate. PMID- 26559521 TI - Novel Predictors of Poor Retention Following a Down-Referral from a Hospital Based Antiretroviral Therapy Program in South Africa. AB - Worldwide, HIV care is becoming increasingly decentralized. For patients in care at centralized facilities, this requires down-referral to local clinics for their HIV care. Information on the real-world experience and predictors of retention in care at the time of down-referral is lacking. We sought to evaluate the effect of patient-level factors on retention in care surrounding a period of down-referral to new clinics for patients with and without virologic failure (VF) on their first-line ART. We conducted a secondary analysis of a case-control study of people living with HIV attending the Sinikethemba (SKT) Clinic at McCord Hospital in Durban, South Africa. Cases (VF) and controls (no VF) responded to a questionnaire focused on individual-level factors. Subsequently, participants self-reported either changing service provider (retained in care), were unable to be reached, died or reported not attending a new provider visit (not retained in care). Multivariate logistic regression was conducted with factors associated with not being retained in care in a univariate analysis. In all, 458 patients were enrolled in the parent study (158 cases and 300 controls) with a median age of 38 years old and with 65% women. A total of 436 (95%) participants successfully established care at the down-referral clinic. In the multivariate analysis, not being pleased with the clinic (SKT), lower adherence scores, and shorter duration of ART predicted failure of down-referral. Down-referral was successful even for patients with VF. Individual-level factors could act as predictors for patients at increased risk for poor retention during the down referral process to a local clinic. PMID- 26559522 TI - Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design. AB - OBJECTIVE: The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. METHODS: The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. RESULTS: SCG-CSNPs exhibited particle size of 200.4 +/- 4.06 nm and %EE of 62.68 +/- 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. CONCLUSIONS: The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs. PMID- 26559523 TI - Social influence and peer review: Why traditional peer review is no longer adapted, and how it should evolve. PMID- 26559524 TI - The meaningless pseudo-category of "GMOs": The trouble with the "new techniques" for genetically modifying crops demonstrates the illogical process-based definition of GMOs in EU regulation. PMID- 26559525 TI - Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells. AB - Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas. PMID- 26559526 TI - Metabolic potential of Bacillus subtilis 168 for the direct conversion of xylans to fermentation products. AB - Methylglucuronoxylans (MeGXn) and methylglucuronoarabinoxylans (MeGAXn) respectively comprise most of the hemicellulose fractions in dicots and monocots and, next to cellulose, are the major resources for the production of fuels and chemicals from lignocellulosics. With either MeGXn or MeGAXn as a substrate, Bacillus subtilis 168 accumulates acidic methylglucuronoxylotriose as a limit product following the uptake and metabolism of neutral xylooligosaccharides. Secreted GH11 endoxylanase (Xyn11A), GH30 endoxylanase (Xyn30C), and GH43 arabinoxylan arabinofuranohydrolase (Axh43) respectively encoded by the xynA, xynC, and xynD genes collectively contribute to the depolymerization of MeGAXn. Studies here demonstrate the complementary roles of these enzymes in the digestion of MeGAXn. Coordinate expression of the xynD and xynC genes defines an operon accounting for the Axh43-catalyzed release of arabinose followed by Xyn30C and Xyn11A-catalyzed depolymerization of MeGAXn. Both sources generate acetate and lactate as the principal fermentation products, with yields of 26 % acetate and 32 % lactate from MeGXn compared to 22 % acetate and 21 % lactate from MeGAXn. These studies of the GH43/GH30/GH11 system in B. subtilis 168 provide a basis for the further development of B. subtilis and related species as biocatalysts for direct conversion of hemicellulose derived from energy crops as well as agricultural and forest residues to chemical feedstocks. PMID- 26559528 TI - Emergence of Asynchronous Local Clocks in Excitable Media. AB - Excitable media such as the myocardium or the brain consist of arrays of coupled excitable elements, in which the local excitation of a single element can propagate to its neighbors in the form of a non-linear autowave. Since each element has to pass through a refractory period immediately after excitation, the frequency of autowaves is self-limiting. In this work, we consider the case where each element is spontaneously excited at a fixed average rate and thereby initiates a new autowave. Although these spontaneous self-excitation events are modelled as independent Poisson point processes with exponentially distributed waiting times, the travelling autowaves lead collectively to a non-exponential, unimodal waiting time distribution for the individual elements. With increasing system size, a global 'clock' period T emerges as the most probable waiting time for each element, which fluctuates around T with an increasingly small but non zero variance. This apparent synchronization between asynchronous, temporally uncorrelated point processes differs from synchronization effects between perfect oscillators interacting in a phase-aligning manner. Finally, we demonstrate that asynchronous local clocks also emerge in non-homogeneous systems in which the rates of self-excitation are different for all individuals, suggesting that this novel mechanism can occur in a wide range of excitable media. PMID- 26559527 TI - Stop and Go - Waves of Tarsier Dispersal Mirror the Genesis of Sulawesi Island. AB - The Indonesian island of Sulawesi harbors a highly endemic and diverse fauna sparking fascination since long before Wallace's contemplation of biogeographical patterns in the region. Allopatric diversification driven by geological or climatic processes has been identified as the main mechanism shaping present faunal distribution on the island. There is both consensus and conflict among range patterns of terrestrial species pointing to the different effects of vicariant events on once co-distributed taxa. Tarsiers, small nocturnal primates with possible evidence of an Eocene fossil record on the Asian mainland, are at present exclusively found in insular Southeast Asia. Sulawesi is hotspot of tarsier diversity, whereby island colonization and subsequent radiation of this old endemic primate lineage remained largely enigmatic. To resolve the phylogeographic history of Sulawesi tarsiers we analyzed an island-wide sample for a set of five approved autosomal phylogenetic markers (ABCA1, ADORA3, AXIN1, RAG1, and TTR) and the paternally inherited SRY gene. We constructed ML and Bayesian phylogenetic trees and estimated divergence times between tarsier populations. We found that their arrival at the Proto-Sulawesi archipelago coincided with initial Miocene tectonic uplift and hypothesize that tarsiers dispersed over the region in distinct waves. Intra-island diversification was spurred by land emergence and a rapid succession of glacial cycles during the Plio-Pleistocene. Some tarsier range boundaries concur with spatial limits in other taxa backing the notion of centers of faunal endemism on Sulawesi. This congruence, however, has partially been superimposed by taxon-specific dispersal patterns. PMID- 26559529 TI - Rifaximin and eluxadoline - newly approved treatments for diarrhea-predominant irritable bowel syndrome: what is their role in clinical practice alongside alosetron? AB - INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence. AREAS COVERED: We review two recently approved therapies that focus on treating underlying pathogenic mechanisms of IBS-D: (1) the non-absorbable antibiotic rifaximin, and (2) the opioid receptor agonist/antagonist eluxadoline. We compare the safety and efficacy data emerging from rifaximin and eluxadoline registration trials with safety and efficacy data from the alosetron clinical development program. EXPERT OPINION: The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles. PMID- 26559530 TI - Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon. AB - In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor's fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source. PMID- 26559531 TI - Depression, Anxiety, Resilience and Coping Pre and Post Kidney Transplantation - Initial Findings from the Psychiatric Impairments in Kidney Transplantation (PI KT)-Study. AB - PURPOSE: Depression/anxiety, impaired Health-Related Quality of Life (HRQoL) and coping and resilience structures, are associated with increased mortality/poor outcome in chronic kidney disease (CKD) patients before (CKD/pre-KT) and after kidney (CKD-T) transplantation. Less is known about prevalence rates of psychiatric symptoms and impaired HRQoL of non-transplanted compared with transplanted patients. METHODS: In a cross-sectional study comparing 101 CKD/pre KT patients with 151 cadaveric-transplanted (CKD-T) patients, we examined prevalence of depression/anxiety (HADS questionnaire) and coping, resilience and HRQoL (SF-12, Resilience-Scale and FKV-questionnaire). RESULTS: The prevalence of both depressive and anxiety symptoms was not significantly different between different pre-/and CKD-T patient groups. In CKD-T no significant relations of coping strategies with kidney function were identified. Furthermore, the Resilience Scales for acceptance and competence did not suggest any differences between the CKD/pre-KT and CKD-T subgroup. In the CKD/pre-KT patients, significant correlations were identified between the acceptance subscale and partnership, as well as between the competence subscale and older age/partnership. CONCLUSIONS: Both the CKD/pre-KT and CKD-T patients exhibited notable impairments in the HRQoL which which showed a comparable pattern of results. KT itself does not appear to be the main risk factor for the development of mental impairments. PMID- 26559532 TI - Union Exon Based Approach for RNA-Seq Gene Quantification: To Be or Not to Be? AB - In recent years, RNA-seq is emerging as a powerful technology in estimation of gene and/or transcript expression, and RPKM (Reads Per Kilobase per Million reads) is widely used to represent the relative abundance of mRNAs for a gene. In general, the methods for gene quantification can be largely divided into two categories: transcript-based approach and 'union exon'-based approach. Transcript based approach is intrinsically more difficult because different isoforms of the gene typically have a high proportion of genomic overlap. On the other hand, 'union exon'-based approach method is much simpler and thus widely used in RNA seq gene quantification. Biologically, a gene is expressed in one or more transcript isoforms. Therefore, transcript-based approach is logistically more meaningful than 'union exon'-based approach. Despite the fact that gene quantification is a fundamental task in most RNA-seq studies, however, it remains unclear whether 'union exon'-based approach for RNA-seq gene quantification is a good practice or not. In this paper, we carried out a side-by-side comparison of 'union exon'-based approach and transcript-based method in RNA-seq gene quantification. It was found that the gene expression levels are significantly underestimated by 'union exon'-based approach, and the average of RPKM from 'union exons'-based method is less than 50% of the mean expression obtained from transcript-based approach. The difference between the two approaches is primarily affected by the number of transcripts in a gene. We performed differential analysis at both gene and transcript levels, respectively, and found more insights, such as isoform switches, are gained from isoform differential analysis. The accuracy of isoform quantification would improve if the read coverage pattern and exon-exon spanning reads are taken into account and incorporated into EM (Expectation Maximization) algorithm. Our investigation discourages the use of 'union exons'-based approach in gene quantification despite its simplicity. PMID- 26559533 TI - The efficacy and safety of systemic injection of Ginkgo biloba extract, EGb761, in idiopathic sudden sensorineural hearing loss: a randomized placebo-controlled clinical trial. AB - Steroids are currently the most frequently accepted agents for idiopathic sudden sensorineural hearing loss (ISSNHL). However, the therapeutic effect of steroids is not always satisfactory. In this pilot study, we evaluated whether systemic treatment with Ginkgo biloba extract (EGb761) has an additive therapeutic effect in patients receiving a systemic steroid due to ISSNHL. A multicenter, randomized, double-blind clinical trial was performed. Fifty-six patients with ISSNHL were allocated to either EGb761 or placebo. In both groups, methylprednisolone was administered for 14 days. EGb761 was infused intravenously for 5 days in the EGb761 group, while the same amount of normal saline was infused in the placebo group. For the efficacy evaluation, pure-tone audiometry, speech audiometry, tinnitus handicap inventory (THI) and short form-36 health (SF 36) survey outcomes were obtained before administration and on days 3, 5, 14 and 28 of administration. Twenty-four patients in each group completed the study protocol. There was no difference in hearing loss between the two groups before treatment. At day 28, air conduction threshold values in the placebo and EGb761 groups were 34.63 +/- 28.90 and 23.84 +/- 25.42 dB, respectively (p = 0.082). Speech discrimination scores in the placebo and EGb761 groups were 69.17 +/- 40.89 and 87.48 +/- 28.65 %, respectively (p = 0.050). THI and SF-36 scores in the placebo and EGb761 groups were similar. Although a combination of steroid and EGb761 for initial treatment did not show better pure tone threshold, compared with steroid alone, speech discrimination was significantly improved in combination therapy. Further studies will be needed to know if addition of EGb761 actually improves the outcome of ISSNHL treatment. PMID- 26559535 TI - Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series. AB - Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations. PMID- 26559536 TI - Change in N-Glycosylation of Plasma Proteins in Japanese Semisupercentenarians. AB - An N-glycomic analysis of plasma proteins was performed in Japanese semisupercentenarians (SSCs) (mean 106.7 years), aged controls (mean 71.6 years), and young controls (mean 30.2 years) by liquid chromatography/mass spectrometry (LC/MS) using a graphitized carbon column. Characteristic N-glycans in SSCs were discriminated using a multivariate analysis; orthogonal projections to latent structures (O-PLS). The results obtained showed that multi-branched and highly sialylated N-glycans as well as agalacto- and/or bisecting N-glycans were increased in SSCs, while biantennary N-glycans were decreased. Since multi branched and highly sialylated N-glycans have been implicated in anti inflammatory activities, these changes may play a role in the enhanced chronic inflammation observed in SSCs. The levels of inflammatory proteins, such as CRP, adiponectin, IL-6, and TNF-alpha, were elevated in SSCs. These results suggested that responses to inflammation may play an important role in extreme longevity and healthy aging in humans. This is the first study to show that the N-glycans of plasma proteins were associated with extreme longevity and healthy aging in humans. PMID- 26559537 TI - Morbidity and mortality revue of the French group of transoral robotic surgery: a multicentric study. AB - Transoral robotic assisted surgery (TORS) represents an innovative endoscopic therapeutic alternative in the treatment of head and neck tumors. Many publications favor this surgery, especially in terms of functional results. The aim of this study was to investigate the TORS morbidity and mortality and to identify the risk factors for complications. It is a multicenter retrospective study. All head and neck tumor patients treated by TORS were included in the study over a period of 5 years (2009-2014). The studied parameters were the intraoperative and post-operative complications including hemorrhage, fistula, tracheotomy, aspiration pneumonia and death. The parameters were correlated with age, tumor location, tumor stage, endoscopic exposure and patient's co morbidities. 178 patients were included in the study. Malignant tumors classified as T1 were found in 169 cases (n = 51), T2 (n = 100), T3 (n = 16) and T4 (n = 2). The tumor locations were distributed as follows: larynx (n = 84), oropharynx (n = 51), and hypopharynx (n = 43). Fifty-three patients followed post-radiation therapy. We observed 12 intraoperative complications including 6 hemorrhage, 3 pharyngeal fistulas and 3 external surgical conversions. Postoperatively, we detected 33 hemorrhage, 27 aspiration pneumonia, 9 tracheostomy, 2 pharyngostomes, 2 cervical spondylitis and 2 deaths. The risk factors identified were (i) anticoagulant and/or antiplatelet therapy for hemorrhage, (ii) tumoral stage and the laryngeal location for aspiration pneumonia and (iii) laryngeal location for tracheostomy. Higher age over 65 years has been identified as a risk factor for all post-operative complications. TORS is a safe technique for the treatment of head and neck tumors. We identified some risk factors for complications which should systematically be studied in order to reduce its morbidity. PMID- 26559538 TI - An experimental study about haptic feedback in robotic surgery: may visual feedback substitute tactile feedback? AB - The aim of this study is to demonstrate the hypothesis that the experience of the surgeon is sufficient to partially compensate for the lack of haptic feedback of the robotic system da Vinci Si HD (Intuitive ((r)) ). Twenty-five international surgeons belonging to different areas of surgical specialization were divided into two groups of investigation: experts and non-experts in the use of da Vinci Platform. This allocation was made on the basis of the following criteria: the number of performed procedures, the number of robotic working days and the number of true console hours. All participants underwent a specific test to assess their ability to recognize the thickness of custom-made membranes, without the availability of haptic feedback. After the performance of the surgeons, score was given according to an appropriate evaluation system (time, preciseness, force of tension and finding a metallic object). The analysis of the performances of participants provided the following results: an average score of 8.87 for the experts compared to 3.57 of non-experts with significant difference (P < 0.05). Other parameters of interest as the average time to conduct the test showed a result of 28.8 s for experts and 71.3 s of non-experts. After our results, a significant difference between the two groups in terms of performance was found. Our hypothesis that the expertise ability of the experts might partially overcome the lack of haptic feedback was confirmed. Probably visual feedback may play a role. PMID- 26559539 TI - Enhanced recovery programme reduces opiate consumption in hip hemiarthroplasty. AB - INTRODUCTION: The enhanced recovery programme (ERP) is used to improve patient experience before, during and after an operation. Initially designed for colorectal surgery, it has now been adopted by many other disciplines, including orthopaedics. Where applicable, ERP has shown to be associated with less pain, reduced length of hospital stay and increased patient satisfaction in elective orthopaedic procedures. There is, however, a paucity of data regarding the use of ERP in fractured neck of femur (NOF) operations. Our aim was to investigate the effect of ERP on analgesic requirements and hospital length of stay during hemiarthroplasty. METHOD: Consecutive notes of 100 patients who received a hemiarthroplasty for a fractured NOF were reviewed retrospectively. In one group (n = 50), patients received routine pre- and post-operative care; the second (n = 50) were on the ERP. All patients were previously mobile with an abbreviated mental test score of more than eight and lived in their own home. RESULTS: With ERP, oral opiate consumption fell dramatically in the first three post-operative days (4.7 vs. 14.0 mg, p > 0.005). The use of patient-controlled analgesia (PCA) was also significantly reduced (odds ratio 0.16, p > 0.05). Although ERP had no statistically significant effect on length of stay (7 vs. 8.5 days, p = 0.2), it saw a greater proportion of patients being discharged back to their own home (25 vs. 19 patients, p < 0.05). CONCLUSION: The ERP reduces post-operative oral opiates and PCA requirements in fractured NOF cases and by inference reduces pain. It does not appear to affect length of hospital stay in an acute unit. PMID- 26559540 TI - Morphometric analysis of the odontoid process: using computed tomography--in the Greek population. AB - AIM: A morphometric analysis of the odontoid process of the A2 vertebra, in the Greek population, was conducted using CT scan. We aimed to determine the feasibility to use one or two screws when treating fractures of this anatomic element. PATIENTS AND METHODS: One hundred and fifteen patients (57 men) of a mean age of 48 years (16-95 years) underwent a cervical spine CT scan examination. The anterior-posterior and transverse diameters of the odontoid process were measured from the base, at 1-mm interval upward on axial CT images. The length from the tip of the odontoid process to the anterior-inferior angle of the body of the axis was calculated. Data concerning the height and weight of the examined patients were collected. RESULTS: The mean transverse and anterior posterior distances were found to be 11.46 and 10.45 mm, respectively, for the upper end of the odontoid process. At the neck level of the odontoid process, the equivalent mean values were 11.12 and 8.73 mm, respectively, while at the base, these distances were found to be 13.84 and 12.3 mm, respectively. The mean distance from the tip of the odontoid to its base was 17.25 and 17.28 mm, respectively, while the mean distance from the tip of the dens to the anterior inferior corner of the axis' body was 39.2 mm. Men showed greater values than women. CONCLUSIONS: In this study, it was shown that in the Greek population there is enough room for one 4.5-mm or one 3.5-mm cannulated screw to be used. The application of two 3.5-mm screws is feasible in 58.6 % of the male and 26.3 % of the female population. This confirms that the knowledge of the true dimensions of the odontoid process is of paramount importance before the proper management of fractured dens using the anterior screw technique. PMID- 26559541 TI - Prevalence of asymptomatic bacteriuria in knee arthroplasty patients and subsequent risk of prosthesis infection. AB - INTRODUCTION: The risk of knee arthroplasty infection and appropriateness of antibiotic treatment are not clearly established in patients with preoperative asymptomatic bacteriuria. It has been the purpose to analyze the prevalence of preoperative asymptomatic bacteriuria in knee arthroplasty patients, as well as the incidence of prosthetic joint infection in those with asymptomatic bacteriuria treated and not with specific antibiotics. PATIENTS AND METHODS: This prospective study included 215 consecutive knee arthroplasty patients (73 +/- 6 years, 168 females) with neither urinary symptoms nor perioperative urethral catheterization. A "clean-catch" urinalysis was obtained from all patients before surgery and an urine culture if urinalysis was abnormal. Asymptomatic bacteriuria was diagnosed if >100,000 colony-forming units/ml were cultured. Patients were treated (Group A) or not (Group B) with additional specific antibiotics for urine bacteria according to surgeon criteria. Minimum follow-up reached 48 months. No patient was lost to follow-up. RESULTS: Asymptomatic bacteriuria was diagnosed in 11/215 patients (5.1 %) (11/11 females), and four of these 11 were treated with specific antibiotics (Group A). Only one patient in Group A suffered a prosthesis infection along the first 3 months (1/125, 0.5 %), but bacteria cultured from the wound were absolutely different to those in urine culture. No patient in Group B suffered a prosthesis infection. CONCLUSIONS: Asymptomatic bacteriuria presents a low prevalence. We have not found any case of arthroplasty infection from urinary focus in patients with asymptomatic bacteriuria whether they received or not specific antibiotics. PMID- 26559542 TI - Management of acute unstable distal clavicle fracture with a modified coracoclavicular stabilization technique using a bidirectional coracoclavicular loop system. AB - BACKGROUND: Fracture of the distal clavicle is not uncommon. Despite the vast literature available for the management of this fracture, there is no consensus regarding the gold standard treatment for this fracture. PURPOSE: To assess the clinical and radiographic outcomes and complications of acute unstable distal clavicle fracture when treated by a modified coracoclavicular stabilization technique using a bidirectional coracoclavicular loop system. METHODS: Thirty nine patients (32 males, 7 females) with acute unstable distal clavicle fractures treated by modified coracoclavicular stabilization using the surgical technique of bidirectional coracoclavicular (CC) loops seated behind the coracoacromial (CA) ligament were retrospectively reviewed. Mean follow-up time was 35.7 months (range 24-47 months). The outcomes measured included union rate, union time, CC distances when compared to the patients' uninjured shoulders, and the Constant and ASES shoulder scores, which were evaluated 6 months after surgery. RESULTS: All fractures displayed clinical union within 13 weeks postoperatively. The mean union time was 9.2 weeks (range 7-13 weeks). At the time of union, the CC distances on the affected shoulders were on average 0.9 mm (range 0-1.6 mm) longer than the unaffected shoulders. At 6 months after surgery, the Constant and ASES scores were on average 93.4 (72-100) and 91.5 (75-100), respectively. No complications related to the fixation loops, musculocutaneous nerve injuries, or fractures of coracoid or clavicle were recorded. One case of surgical wound dehiscence was observed due to superficial infection. Enlargement of the clavicle drill hole without migration of the buttons was observed in 9 out of 16 cases at a follow-up time of at least 30 months after the original operation. CONCLUSIONS: Modified CC stabilization using bidirectional CC loops seated behind the CA ligament is a simple surgical technique that naturally restores stability to the distal clavicle fracture. It also produces predictable outcomes, a high union rate, good to excellent shoulder function, and a low complication rate. The buttons and suture loops were routinely removed in a second operation in order to prevent late stress fracture of the clavicle. PMID- 26559543 TI - Propentofylline inhibits glioblastoma cell invasion and survival by targeting the TROY signaling pathway. AB - Glioblastoma (GBM) is the most common primary tumor of the CNS and carries a dismal prognosis. The aggressive invasion of GBM cells into the surrounding normal brain makes complete resection impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Median survival for newly diagnosed GBM is 14.6 months and declines to 8 months for patients with recurrent GBM. New therapeutic strategies that target the molecular drivers of invasion are required for improved clinical outcome. We have demonstrated that TROY (TNFRSF19), a member of the TNFR super family, plays an important role in GBM invasion and resistance. Knockdown of TROY expression inhibits GBM cell invasion, increases sensitivity to temozolomide, and prolongs survival in an intracranial xenograft model. Propentofylline (PPF), an atypical synthetic methylxanthine compound, has been extensively studied in Phase II and Phase III clinical trials for Alzheimer's disease and vascular dementia where it has demonstrated blood-brain permeability and minimal adverse side effects. Here we showed that PPF decreased GBM cell expression of TROY, inhibited glioma cell invasion, and sensitized GBM cells to TMZ. Mechanistically, PPF decreased glioma cell invasion by modulating TROY expression and downstream signaling, including AKT, NF-kappaB, and Rac1 activation. Thus, PPF may provide a pharmacologic approach to target TROY, inhibit cell invasion, and reduce therapeutic resistance in GBM. PMID- 26559545 TI - Immortal time bias. Response to: Achinger, Go and Ayus. PMID- 26559544 TI - Cohort Profile: The Kiang West Longitudinal Population Study (KWLPS)-a platform for integrated research and health care provision in rural Gambia. PMID- 26559546 TI - Pregnancy history and risk of premenopausal breast cancer-a nested case-control study. AB - BACKGROUND: Reproductive factors are well-known risk factors for premenopausal breast cancer (PBC). It is unknown whether these associations are modified by familial factors, including genetic and early environment factors. METHODS: Using Swedish health registries, we performed a nested case-control study with two control groups: sister controls and population controls. The study population included women with live singleton births between 1973 and 2010, who also had a full sister who gave birth during this period. All women subsequently diagnosed with PBC were selected as cases (n = 8327). Sisters with the least age difference and without PBC at the time of her sister's diagnosis were selected as sister controls. For each incident case, one population control without previous PBC was selected.The population controls were individually matched with the sister controls on year of birth. Conditional logistic regression was used to estimate associations between reproductive factors and PBC. RESULTS: Increasing parity was inversely associated with PBC using population controls, and multiparity was a risk factor using sister controls. Very preterm delivery (<= 31 weeks) was associated with a slightly higher PBC risk using sister controls. Preeclampsia was associated with a slightly protective effect using population controls. With respect to other factors, there were no substantial differences in risks of PBC by choice of control group. CONCLUSIONS: The divergent results with regard to parity and PBC risk when using sister and population controls suggest that the influence of childbearing may be modified by genotype. Selection bias when using different control groups must also be considered. PMID- 26559547 TI - Psychiatric epidemiology: dimensions and categories. PMID- 26559548 TI - How to approach the great mimic? Improving techniques for the diagnosis of myocarditis. AB - Myocarditis is characterized by inflammation of the myocardium, assessed by histological, immunological and immunohistochemical criteria, due to exogenous or endogenous causes. Abnormal QRS, increased troponin T and left ventricular regional or global dysfunction may be detected. Strain Doppler echocardiography can detect longitudinal segmental dysfunction of the myocardium, due to edema, which is in agreement with cardiac magnetic resonance imaging. Nuclear imaging shows a good sensitivity, but carries serious limitations. Somatostatin receptor positron emission tomography/computed tomography seems promising. Cardiac magnetic resonance imaging, using T2-weighted, early T1-weighted, delayed enhanced images and recently T2 and T1 mapping, has the best diagnostic capability. Endomyocardial biopsy has further contributed to the etiologic diagnosis of myocarditis. To conclude, cardiac magnetic resonance and endomyocardial biopsy have both significantly increased our diagnostic performance. However, further assessment by multicenter studies is needed to establish a clinically useful algorithm. PMID- 26559549 TI - Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis. AB - Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary. PMID- 26559550 TI - Quantum Dots and their Potential Role in Cancer Theranostics. AB - The emergence of cancer nanomedicine is the result of fruitful advances in the fields of nanotechnology, bioimaging, formulation development, and molecular biology. Quantum dots (QDs) are the luminescent nanocrystals (NCs) that provide a multifunctional platform for imaging the biosystems following controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. These engineered fluorescent probes with integrated imaging and carrier functionalities have become excellent tools for molecular diagnostics and delivery of therapeutics molecules. Flexible surface chemistry, unique optical properties, high sensitivity, and multiplexing capabilities of QDs certainly make them a most promising tool for personalized medicine. This review focuses on state-of-art advances in synthesizing QDs and highlights the approaches used for functionalization of QDs with desired ligands for targeted carriage to specific sites. Discussed is the role of QDs in antitumor therapy through drug delivery and gene delivery and the recently emerged photodynamic therapy (PDT). We also endeavor to critically address the major impediments in the clinical development of these multifunctional nanoplatforms, with a special focus on plausible advancements for the near future. PMID- 26559551 TI - Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS. AB - In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID- 26559552 TI - Emerging Potential of Nanosuspension-Enabled Drug Delivery: An Overview. AB - Poor aqueous solubility is one of the key concerns of the majority of new drug molecules. One of the important problems associated with such drugs is that they often lead to low bioavailability. Researchers have used various techniques, but little success has been achieved due to poor stability and industrial viability, including technique cost. Of the numerous techniques, nanosuspensions (NSs) have drawn interest in improving solubility. NSs are dispersions of nanosized drug particles stabilized with the aid of appropriate agents. Stabilizers for NSs are generally recognized as safe (GRAS) excipients that can be chosen from a number of surfactants and/or polymers to food proteins. The commonly used techniques for preparation of NSs including top-down and bottom-up methods, along with new fabrication techniques based on supercritical (SC) fluids, are reviewed. This review also includes preparatory techniques, characterization, potential applications, and recent advancements in the field of NSs. PMID- 26559553 TI - Microbial quality and molecular identification of cultivable microorganisms isolated from an urban drinking water distribution system (Limassol, Cyprus). AB - Microorganisms can survive and multiply in aged urban drinking water distribution systems, leading to potential health risks. The objective of this work was to investigate the microbial quality of tap water and molecularly identify its predominant cultivable microorganisms. Tap water samples collected from 24 different households scattered in the urban area of Limassol, Cyprus, were microbiologically tested following standard protocols for coliforms, E. coli, Pseudomonas spp., Enterococcus spp., and total viable count at 22 and 37 degrees C. Molecular identification was performed on isolated predominant single colonies using 16SrRNA sequencing. Approximately 85% of the household water samples were contaminated with one or more microorganisms belonging to the genera of Pseudomonas, Corynebacterium, Agrobacterium, Staphylococcus, Bacillus, Delftia, Acinetobacter, Enterococcus, Enterobacter, and Aeromonas. However, all samples tested were free from E. coli. This is the first report in Cyprus molecularly confirming specific genera of relevant microbial communities in tap water. PMID- 26559554 TI - Combining biological and geomorphological data to introduce biotopes of Bushehr Province, the Persian Gulf. AB - Identification and classification of intertidal areas provides the basic knowledge needed for studies of biogeography, macro-ecology, and faunal populations, as well as for conservation planning and managing human activities in coastal areas. In this research, the eastern coast of Bushehr Province was classified using the Coastal and Marine Ecological Classification Standard (CMECS). Seven substrate subgroups, five geoform types in unconsolidated mineral substrate, five micro-habitats in rock substrate, and nine biotic groups were identified in study stations. The non-metric multidimensional scaling (nMDS) ordinations and one-way analysis of similarity (ANOSIM) showed that macroinvertebrate species composition differed significantly among different geoform types (habitat types). Eight biotopes are introduced for the eastern coast of Bushehr Province based on observational and statistical methods. The results presented here show that identifying intertidal biotopes using CMECS is an appropriate method both for classifying the southern coastal areas of Iran and for integrating biotic and abiotic components. PMID- 26559555 TI - Comparative study of heavy metals concentration in topsoil of urban green space and agricultural land uses. AB - The main objective of this study was to determine the concentration of cadmium, chromium, copper, nickel, lead, and zinc in surface soils of two land uses including agricultural and urban green space in Semnan Province, Iran. For this purpose, the soil samples of 27 urban green space and 47 agricultural fields were collected and analyzed. The correlation coefficients, analysis of variance, principal component analysis, cluster analysis, and geoaccumulation index were utilized to compare the mean values in the two land uses and pinpoint the possible sources of contamination in the study area. The average contents of Cd, Cu, Cr, Ni, Pb, and Zn in green space soils were 0.1, 24.9, 78.7, 28.2, 22.1, and 82.1 mg/kg, respectively, while the mean concentrations of Cd, Cu, Cr, Ni, Pb, and Zn in agricultural soils were 0.3, 24.3, 83.7, 33.3, 18.1, and 80.4 mg/kg, respectively. The mean concentrations of lead, copper, and zinc were higher in urban green space in comparison with those of agricultural fields, while it was vice versa for chromium, cadmium, and nickel. In general, significant, but weak, correlations were observed between Zn with Pb (r = 0.53) and Cu (r = 0.61) and Ni with Cr (r = 0.55) and Cu(r = 0.51). The main sources of contamination turned out to be both natural and anthropogenic as the results of correlation coefficients, principal component analysis, and cluster analysis showed. That is to say, chromium and nickel had emanated from natural while the sources of cadmium, lead, and zinc could be attributed to anthropogenic activities. For the case of copper, both natural and anthropogenic activities were influential; however, the role of human activities was more effective. The results of contamination assessment showed that heavy metal contamination in agricultural land use was higher than green space indicating the role of human activities in this respect. PMID- 26559556 TI - An optical method to assess water clarity in coastal waters. AB - Accurate estimation of water clarity in coastal regions is highly desired by various activities such as search and recovery operations, dredging and water quality monitoring. This study intends to develop a practical method for estimating water clarity based on a larger in situ dataset, which includes Secchi depth (Z sd ), turbidity, chlorophyll and optical properties from several field campaigns in turbid coastal waters. The Secchi depth parameter is found to closely vary with the concentration of suspended sediments, vertical diffuse attenuation coefficient K d (m(-1)) and beam attenuation coefficient c (m(-1)). The optical relationships obtained for the selected wavelengths (i.e. 520, 530 and 540 nm) exhibit an inverse relationship between Secchi depth and the length attenuation coefficient (1/(c + K d )). The variation in Secchi depth is expressed in terms of undetermined coupling coefficient which is composed of light penetration factor (expressed by z(1%)K d (lambda)) and a correction factor (xi) (essentially governed by turbidity of the water column). This method of estimating water clarity was validated using independent in situ data from turbid coastal waters, and its results were compared with those obtained from the existing methods. The statistical analysis of the measured and the estimated Z sd showed that the present method yields lower error when compared to the existing methods. The spatial structures of the measured and predicted Z sd are also highly consistent with in situ data, which indicates the potential of the present method for estimating the water clarity in turbid coastal and associated lagoon waters. PMID- 26559557 TI - Analysis of DDT and its metabolites in soil and water samples obtained in the vicinity of a closed-down factory in Bangladesh using various extraction methods. AB - This study was conducted to monitor the spread of dichlorodiphenyltrichloroethane (DDT) and its metabolites (dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD)) in soil and water to regions surrounding a closed DDT factory in Bangladesh. This fulfillment was accomplished using inter method and inter-laboratory validation studies. DDTs (DDT and its metabolites) from soil samples were extracted using microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), and solvent extraction (SE). Inter laboratory calibration was assessed by SE, and all methods were validated by intra- and inter-day accuracy (expressed as recovery %) and precision (expressed as relative standard deviation (RSD)) in the same laboratory, at three fortified concentrations (n = 4). DDTs extracted from water samples by liquid-liquid partitioning and all samples were analyzed by gas chromatography (GC)-electron capture detector (ECD) and confirmed by GC/mass spectrometry (GC/MS). Linearities expressed as determination coefficients (R (2)) were >=0.995 for matrix-matched calibrations. The recovery rate was in the range of 72-120 and 83-110%, with <15% RSD in soil and water, respectively. The limit of quantification (LOQ) was 0.0165 mg kg(-1) in soil and 0.132 MUg L(-1) in water. Greater quantities of DDTs were extracted from soil using the MAE and SE techniques than with the SFE method. Higher amounts of DDTs were discovered in the southern (2.2-936 * 10(2) mg kg( 1)) or southwestern (86.3-2067 * 10(2) mg kg(-1)) direction from the factory than in the eastern direction (1.0-48.6 * 10(2) mg kg(-1)). An exception was the soil sample collected 50 ft (15.24 m) east (2904 * 10(2) mg kg(-1)) of the factory. The spread of DDTs in the water bodies (0.59-3.01 MUg L(-1)) was approximately equal in all directions. We concluded that DDTs might have been dumped randomly around the warehouse after the closing of the factory. PMID- 26559558 TI - Limited ability of circulating anti-Mullerian hormone to predict dominant follicular recruitment in PCOS women treated with clomiphene citrate: a comparison of two different assays. AB - The present retrospective cohort study was conducted to investigate whether serum anti-Mullerian hormone (AMH) levels, determined by either the Immunotech (IOT) or the second generation (Gen II) assay, can predict follicular recruitment in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). Patients received 50 mg CC daily for ovulation induction followed by natural intercourse or intrauterine insemination. Overall, 84 women had their serum AMH levels tested before treatment [42 patients with Immunotech (IOT), and 42 patients with the Gen II assay]. The primary outcome was to determine dominant follicle (>10 mm) recruitment in relation to AMH levels. Thirty-three (79%) patients in the IOT and 34 (81%) patients in the Gen II assay group developed a dominant follicle within 15 days after initiation of CC. Circulating AMH levels did not differ between women with or without dominant follicular recruitment in the both groups. By using either the AMH IOT or the Gen II assay, serum AMH levels were not predictive of the development of a dominant follicle. In conclusion, serum AMH levels measured by IOT or Gen II assay, has limited value to predict PCOS patients who will develop a dominant follicle following ovulation induction with CC. PMID- 26559559 TI - Dabigatran in 'real-world' clinical practice for stroke prevention in patients with non-valvular atrial fibrillation. PMID- 26559560 TI - Myoclonic status and central fever in Angelman syndrome due to paternal uniparental disomy. AB - Myoclonic status in nonprogressive encephalopathy (MSNE) is an early-onset, drug resistant epileptic syndrome characterized by occurrence of continuous diffuse epileptiform abnormalities, associated with positive and/or negative phenomena and accompanied by transient and recurring motor, cognitive, and behavioral impairment. MSNE has been reported in Angelman syndrome (AS) secondary to 15q11 13 deletions or UBE3A mutations but not to paternal uniparental disomy (UPD). We describe the case of a male patient with AS caused by UPD who developed a myoclonic status (MS) associated with long-lasting fever of central origin, both promptly regressed with introduction of levetiracetam. Only three descriptions of thermal dysregulation in AS exist, and none of the previously reported cases were associated with MS or with UPD. Association of MS and central fever expands the spectrum of epileptic and non-epileptic features in UPD-related AS and provides a further evidence of hypothalamus involvement in the pathogenesis of this neurodevelopmental disorder. PMID- 26559561 TI - Immunosuppressive drug therapy for preventing rejection following lung transplantation in cystic fibrosis. AB - BACKGROUND: For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry to obtain information on unpublished and ongoing studies.Date of latest search: 19 May 2015. SELECTION CRITERIA: Randomised and quasi-randomised studies. DATA COLLECTION AND ANALYSIS: We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. MAIN RESULTS: While two studies met our inclusion criteria, we did not include them in the review because the investigators of the studies did not report any information specific to people with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future updates of the review. AUTHORS' CONCLUSIONS: The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A recent Cochrane review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation. PMID- 26559562 TI - Lower thoracic rib stress fractures in baseball pitchers. AB - Stress fractures of the first rib on the dominant throwing side are well described in baseball pitchers; however, lower thoracic rib fractures are not commonly recognized. While common in other sports such as rowing, there is scant literature on these injuries in baseball. Intercostal muscle strains are commonly diagnosed in baseball pitchers and have a nearly identical presentation but also a highly variable healing time. The diagnosis of a rib stress fracture can predict a more protracted recovery. This case series presents two collegiate baseball pitchers on one team during the same season who were originally diagnosed with intercostal muscle strains, which following magnetic resonance imaging (MRI) were found to have actually sustained lower thoracic rib stress fractures. The first sustained a stress fracture of the posterior aspect of the right 8th rib on the dominant arm side, while the second presented with a left sided 10th rib stress fracture on the nondominant arm side. In both cases, MRI was used to visualize the fractures as plain radiographs are insensitive and commonly negative early in patient presentation. Patients were treated with activity modification, and symptomatic management for 4-6 weeks with a graduated return to throwing and competition by 8-10 weeks. The repetitive high stresses incurred by pitching may cause either dominant or nondominant rib stress fractures and this should be included in the differential diagnosis of thoracic injuries in throwers. It is especially important that athletic trainers and team physicians consider this diagnosis, as rib fractures may have a protracted course and delayed return to play. Additionally, using the appropriate imaging techniques to establish an accurate diagnosis can help inform return-to-play decisions, which have important practical applications in baseball, such as roster management and eligibility. PMID- 26559563 TI - Influence of miRNA-106b and miRNA-135a on butyrate-regulated expression of p21 and Cyclin D2 in human colon adenoma cells. AB - Epigenetic and posttranslational modifications of the expression of cell cycle relevant genes or proteins like p21, e.g., by miRNAs are crucial mechanisms in the development or prevention of colon cancer. The present study investigated the influence of butyrate and trichostatin A (TSA) as histone deacetylase inhibitors on the expression of colon cancer-relevant miRNA (miR-135a, miR-135b, miR-24, miR 106b, miR-let-7a) in LT97 colon adenoma cells as a model of an early stage of colon carcinogenesis. The impact of distinct miRNAs (miR-106b, miR-135a) on butyrate-mediated regulation of p21 and Cyclin D2 gene and protein expression as well as the effect on LT97 cell proliferation (non-transfected, miR-106b and miR 135a mimic transfected) was analyzed. Butyrate and partial TSA reduced the expression of miR-135a, miR-135b, miR-24 and miR-let-7a (~0.5-fold, 24 h) and miR 24, miR-106b and miR-let-7a (~0.5-0.7-fold, 48 h) in LT97 cells. Levels of p21 mRNA and protein were significantly increased by butyrate and TSA (~threefold and 4.5-fold, respectively, 24 h) in non-transfected but not in miR-106b transfected LT97 cells. Levels of Cyclin D2 mRNA were significantly reduced by butyrate and TSA (~0.3-fold, 24 h) in non-transfected and miR-135a-transfected LT97 cells, whereas protein levels were predominantly not influenced. MiR-106b and miR-135a significantly reduced butyrate-/TSA-mediated inhibition of LT97 cell proliferation (72 h). These results indicate that butyrate is able to modify colon cancer-relevant miRNAs like miR-106b and miR-135a which are involved in the regulation of cell cycle-relevant genes like p21 and might influence inhibition of adenoma cell proliferation. PMID- 26559565 TI - The role of copper in the thermal conductivity of thermoelectric oxychalcogenides: do lone pairs matter? AB - Understanding the underlying mechanisms that suppress thermal conduction in solids is of paramount importance for the targeted design of materials for thermal management and thermoelectric energy conversion applications. Bismuth copper oxychalcogenides, BiOCuQ (Q = Se, Te), are highly crystalline thermoelectric materials with an unusually low lattice thermal conductivity of ~0.5 Wm(-1) K(-1), a value normally found in amorphous materials. Here we unveil the origin of the unusual thermal transport properties of these phases. First principles calculations of the vibrational properties combined with analysis of in-situ neutron diffraction data, demonstrate that weak bonding of copper atoms within the structure leads to an unexpected vibrational mode at low frequencies, which is likely to be a major contributor to the low thermal conductivity of these materials. In addition, we show that anharmonicity and the large Gruneisen parameter in these oxychalcogenides are mainly related to the low frequency copper vibrations, rather than to the Bi(3+) lone pairs. PMID- 26559564 TI - From institutionalization of user fees to their abolition in West Africa: a story of pilot projects and public policies. AB - This article analyzes the historical background of the institutionalization of user fees and their subsequent abolition in West Africa. Based on a narrative review, we present the context that frames the different articles in this supplement. We first show that a general consensus has emerged internationally against user fees, which were imposed widely in Africa in the 1980s and 1990s; at that time, the institutionalization of user fees was supported by evidence from pilot projects funded by international aid agencies. Since then there have been other pilot projects studying the abolition of user fees in the 2000s, but these have not yet had any real influence on public policies, which are often still chaotic. This perplexing situation might be explained more by ideologies and political will than by insufficient financial capacity of states. PMID- 26559566 TI - Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli. AB - The resistance-nodulation-division (RND) family efflux pumps are important in the antibiotic resistance of Gram-negative bacteria. However, although a number of bacterial RND efflux pump inhibitors have been developed, there has been no clinically available RND efflux pump inhibitor to date. A set of BSN-coded 2 substituted benzothiazoles were tested alone and in combinations with ciprofloxacin (CIP) against the AcrAB-TolC overexpressor Escherichia coli AG102 clinical strain. The results indicated that the BSN compounds did not show intrinsic antimicrobial activity when tested alone. However, when used in combinations with CIP, a reversal in the antibacterial activity of CIP with up to 10-fold better MIC values was observed. In order to describe the binding site features of these BSN compounds with AcrB, docking studies were performed using the CDocker method. The performed docking poses and the calculated binding energy scores revealed that the tested compounds BSN-006, BSN-023, and BSN-004 showed significant binding interactions with the phenylalanine-rich region in the distal binding site of the AcrB binding monomer. Moreover, the tested compounds BSN-006 and BSN-023 possessed stronger binding energies than CIP, verifying that BSN compounds are acting as the putative substrates of AcrB. PMID- 26559567 TI - The most effective and promising population health strategies to advance human papillomavirus vaccination. AB - The US is failing to make substantive progress toward improving rates of human papillomavirus vaccine uptake. While the Healthy People 2020 goal for human papillomavirus (HPV) vaccination is 80%, the three-dose completion rate in the US in 2014 for 13- to 17-year-old females is less than 40%, and the rate for males is just above 20%. Experts point to a number of reasons for the poor HPV vaccination rates including parental concerns about safety, necessity, and timing. However, the evidence refuting these concerns is substantial. Efforts focusing on education and communication have not shown promise, but several population health strategies have reminder/recall systems; practice-focused strategies targeting staff, clinicians, and parents; assessment and feedback activities; and school-based HPV vaccination programs. PMID- 26559568 TI - Reviewing Peer Review at the NIH. AB - Recent reports suggest that peer reviews of National Institutes of Health grant applications are at best imprecise predictors of research projects' scientific impact. But these findings may not mean that peer review is failing. PMID- 26559569 TI - The Path to Cancer --Three Strikes and You're Out. AB - Focusing on driver-gene mutations and the pathways they control has rendered complex cancer-genome landscapes intelligible. In solid tumors of adults, alterations in as few as three driver genes appear to suffice for a cell to evolve into an advanced cancer. PMID- 26559570 TI - Maryland's Global Hospital Budgets--Preliminary Results from an All-Payer Model. AB - In the first year of Maryland's experiment in setting all-payer rates for hospital services, costs were contained and the quality of care improved, though the state still has high rates of hospital admissions and per capita spending for Medicare patients. PMID- 26559573 TI - Elder Abuse. AB - Because older victims of abuse tend to be isolated, their interactions with physicians are important opportunities to recognize abuse and intervene. This review explores the manifestations of elder abuse and the role of multidisciplinary teams in its assessment and management. PMID- 26559571 TI - The Genetic Evolution of Melanoma from Precursor Lesions. AB - BACKGROUND: The pathogenic mutations in melanoma have been largely catalogued; however, the order of their occurrence is not known. METHODS: We sequenced 293 cancer-relevant genes in 150 areas of 37 primary melanomas and their adjacent precursor lesions. The histopathological spectrum of these areas included unequivocally benign lesions, intermediate lesions, and intraepidermal or invasive melanomas. RESULTS: Precursor lesions were initiated by mutations of genes that are known to activate the mitogen-activated protein kinase pathway. Unequivocally benign lesions harbored BRAF V600E mutations exclusively, whereas those categorized as intermediate were enriched for NRAS mutations and additional driver mutations. A total of 77% of areas of intermediate lesions and melanomas in situ harbored TERT promoter mutations, a finding that indicates that these mutations are selected at an unexpectedly early stage of the neoplastic progression. Biallelic inactivation of CDKN2A emerged exclusively in invasive melanomas. PTEN and TP53 mutations were found only in advanced primary melanomas. The point-mutation burden increased from benign through intermediate lesions to melanoma, with a strong signature of the effects of ultraviolet radiation detectable at all evolutionary stages. Copy-number alterations became prevalent only in invasive melanomas. Tumor heterogeneity became apparent in the form of genetically distinct subpopulations as melanomas progressed. CONCLUSIONS: Our study defined the succession of genetic alterations during melanoma progression, showing distinct evolutionary trajectories for different melanoma subtypes. It identified an intermediate category of melanocytic neoplasia, characterized by the presence of more than one pathogenic genetic alteration and distinctive histopathological features. Finally, our study implicated ultraviolet radiation as a major factor in both the initiation and progression of melanoma. (Funded by the National Institutes of Health and others.). PMID- 26559574 TI - Images in Clinical Medicine. Left Main Coronary Artery Stent Migration. AB - A 22-year-old woman with primary pulmonary hypertension presented with displacement of stents that had been implanted in the left main coronary artery and had migrated into the aorta. She had been referred to our center for evaluation for lung transplantation. PMID- 26559572 TI - Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease. AB - BACKGROUND: Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years. METHODS: We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics. RESULTS: Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76). CONCLUSIONS: During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA Cooperative Studies Program and others; COURAGE ClinicalTrials.gov number, NCT00007657.). PMID- 26559575 TI - Case Records of the Massachusetts General Hospital. Case 35-2015: A 72-Year-Old Woman with Proteinuria and a Kidney Mass. AB - A 72-year-old woman presented with flank pain, proteinuria, and a new kidney mass. Magnetic resonance imaging of the kidney revealed a complex, solid mass (3 cm x 2.9 cm x 2.9 cm) in the lower pole of the right kidney. Diagnostic tests were performed. PMID- 26559576 TI - Targeting Stem Cells in Chronic Myeloid Leukemia with a PPAR-gamma Agonist. AB - Combining a tyrosine kinase inhibitor (imatinib) and a thiazolidinedione (pioglitazone) is proposed for the treatment of chronic myeloid leukemia. PMID- 26559577 TI - Troponin in Stable Ischemic Heart Disease and Diabetes. PMID- 26559578 TI - Troponin in Stable Ischemic Heart Disease and Diabetes. PMID- 26559579 TI - Troponin in Stable Ischemic Heart Disease and Diabetes. PMID- 26559580 TI - Troponin in Stable Ischemic Heart Disease and Diabetes. PMID- 26559581 TI - Troponin in Stable Ischemic Heart Disease and Diabetes. PMID- 26559582 TI - PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. PMID- 26559583 TI - PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. PMID- 26559584 TI - Tenofovir Gel to Prevent HSV-2 Infection. PMID- 26559585 TI - Tenofovir Gel to Prevent HSV-2 Infection. PMID- 26559586 TI - Tenofovir Gel to Prevent HSV-2 Infection. PMID- 26559587 TI - Persistent Ebola Virus in the Eye. PMID- 26559588 TI - Persistent Ebola Virus in the Eye. PMID- 26559589 TI - Persistent Ebola Virus in the Eye. PMID- 26559590 TI - Case 23-2015: A Woman with Headache, Cognitive Impairment, and Weakness. PMID- 26559591 TI - Case 23-2015: A Woman with Headache, Cognitive Impairment, and Weakness. PMID- 26559592 TI - Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. PMID- 26559593 TI - Biallelic NTHL1 Mutations in a Woman with Multiple Primary Tumors. AB - A patient is described with multiple cancers and compound heterozygous mutations in NTHL1, a recently described polyposis gene. The involvement of a second causative mutation is reported. PMID- 26559595 TI - Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer. PMID- 26559594 TI - Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis. AB - Treatment of multidrug-resistant Mycobacterium tuberculosis is a challenge. This letter describes the emergence of resistance to new therapies, bedaquiline and delamanid. PMID- 26559596 TI - Images in Clinical Medicine. Central Retinal-Vein Occlusion. AB - A 43-year-old man presented with sudden painless loss of vision in his left eye. Funduscopic examination revealed hyperemia and swelling of the optic nerve, macular edema, diffuse intraretinal hemorrhages, and dilated and tortuous retinal veins. PMID- 26559597 TI - How concerns and experiences with medical malpractice affect dermatopathologists' perceptions of their diagnostic practices when interpreting cutaneous melanocytic lesions. AB - OBJECTIVE: We sought to identify characteristics associated with past malpractice lawsuits and how malpractice concerns may affect interpretive practices. METHODS: We surveyed 207 of 301 (68.8%) eligible dermatopathologists who interpret melanocytic skin lesions in 10 states. The survey assessed dermatopathologists' demographic and clinical practice characteristics, perceptions of how medical malpractice concerns could influence their interpretive practices, and past malpractice lawsuits. RESULTS: Of dermatopathologists, 33% reported past malpractice experiences. Factors associated with being sued included older age (57 vs 48 years, P < .001), lack of board certification or fellowship training in dermatopathology (76.5% vs 53.2%, P = .001), and greater number of years interpreting melanocytic lesions (>20 years: 52.9% vs 20.1%, P < .001). Of participants, 64% reported being moderately or extremely confident in their melanocytic interpretations. Although most dermatopathologists believed that malpractice concerns increased their likelihood of ordering specialized pathology tests, obtaining recuts, and seeking a second opinion, none of these practices were associated with past malpractice. Most dermatopathologists reported concerns about potential harms to patients that may result from their assessments of melanocytic lesions. LIMITATIONS: Limitations of this study include lack of validation of and details about the malpractice suits experienced by participating dermatopathologists. In addition, the study assessed perceptions of practice rather than actual practices that might be associated with malpractice incidents. CONCLUSIONS: Most dermatopathologists reported apprehension about how malpractice affects their clinical practice and are concerned about patient safety irrespective of whether they had actually experienced a medical malpractice suit. PMID- 26559598 TI - A cross flow-through pedicle free latissimus dorsi flap for high voltage electrical burns. AB - BACKGROUND: The management of a high voltage electrical injury and lower limb salvage remains a challenging task for plastic surgeons. Reconstruction with flaps is often the only alternative to limb amputation. The purpose of this study was to present a cross flow-through pedicle free latissimus dorsi muscle flap for the salvage of severely traumatized lower limbs perfused by one remaining vessel (a single vessel lower limb) in high voltage electrical injuries. METHODS: In this retrospective study, between 2000 and 2014, six men underwent cross-leg free Latissimus dorsi muscle flap operations for limb salvage. They had soft tissue lower leg defects due to high voltage electrical injuries. Their medical records were retrospectively reviewed. All had only one artery that perfused the leg. Free pedicled thoracodorsal artery latissimus dorsi flaps were harvested and connected to the contralateral posterior tibial artery. RESULTS: All defects were successfully covered. No flap loss or major amputation occurred during follow-up (mean; 5.9 years). A computerized tomography angiogram showed intact vessel continuity in the recipient vascular system. The patients were able to walk without any apparatus or assistance after long term follow-up. CONCLUSION: We recommend that the cross flow-through pedicle free muscle flap should be considered as a salvage procedure for single vessel lower extremities resulting from high voltage electrical burns. Extremity perfusion was not compromised by this procedure. PMID- 26559599 TI - Landrace Germplasm for Improving Yield and Abiotic Stress Adaptation. AB - Plant landraces represent heterogeneous, local adaptations of domesticated species, and thereby provide genetic resources that meet current and new challenges for farming in stressful environments. These local ecotypes can show variable phenology and low-to-moderate edible yield, but are often highly nutritious. The main contributions of landraces to plant breeding have been traits for more efficient nutrient uptake and utilization, as well as useful genes for adaptation to stressful environments such as water stress, salinity, and high temperatures. We propose that a systematic landrace evaluation may define patterns of diversity, which will facilitate identifying alleles for enhancing yield and abiotic stress adaptation, thus raising the productivity and stability of staple crops in vulnerable environments. PMID- 26559600 TI - The Associations Between Body Cell Mass and Nutritional and Inflammatory Markers in Patients With Chronic Kidney Disease and in Subjects Without Kidney Disease. AB - OBJECTIVES: Body cell mass (BCM), a component of lean tissue mass (LTM), is a metabolically active part of the body. Lean tissue loss is one of the diagnostic criteria of protein energy wasting. In patients with chronic kidney disease (CKD), a decrease of lean tissue, including BCM, may be replaced by an increase of extracellular water. Bioimpedance spectroscopy (BIS) enables the assessment of the amount of BCM, LTM, and fluid overload. The aim of our study was to assess the relationship between BCM measured by BIS and anthropometric measurements, biochemical markers of nutrition and also inflammatory markers. METHODS: Forty eight patients treated with hemodialysis (HD; 32 males and 16 females) with a mean age 59.8 +/- 15.5 (HD group), 61 patients with CKD Stage 4 to 5 (35 males and 26 females) with a mean age of 60.1 +/- 17.7 (predialysis group) and 33 individuals with normal renal function (18 males and 15 women) with a mean age 58.7 +/- 17.0 (control group) were included. Body mass index, handgrip strength (HGS), body composition measured by BIS, and biochemical analyses were performed on all of them. RESULTS: Positive correlations were observed between BCM and LTM, HGS, serum creatinine and insulin-like growth factor 1 concentrations in all groups. Serum prealbumin concentration correlated positively with BCM only in the predialysis group (r = 0.406; P = .001). The amount of lymphocytes also correlated passively with BCM in predialysis group (r = 0.314; P = .024). Negative correlations were noted between BCM and fat mass in all groups and between BCM and interleukin 6 concentrations only in the HD group. In this study, BCM neither correlated with body mass index and serum albumin nor with C-reactive protein. CONCLUSIONS: BCM is strongly associated with biochemical determinants of muscle mass (serum creatinine, insulin-like growth factor 1) and muscle function (HGS) in patients treated with HD, with CKD Stage 4 to 5 and in individuals without kidney disease. Its significance requires further investigation. PMID- 26559601 TI - Driving after an acute coronary syndrome. PMID- 26559602 TI - Label-free colorimetric detection of mercury via Hg(2+) ions-accelerated structural transformation of nanoscale metal-oxo clusters. AB - Mercury and its compounds are known to be extremely toxic but widely distributed in environment. Although many works have been reported to efficiently detect mercury, development of simple and convenient sensors is still longed for quick analyzing mercury in water. In this work, a nanoscale metal-oxo cluster, (n Bu4N)2[Mo5NaO13(OCH3)4(NO)], (MLPOM), organically-derivatized from monolacunary Lindqvist-type polyoxomolybdate, is found to specifically react with Hg(2+) in methanol/water via structural transformation. The MLPOM methanol solution displays a color change from purple to brown within seconds after being mixed with an aqueous solution containing Hg(2+). By comparing the structure of polyoxomolybdate before and after reaction, the color change is revealed to be the essentially structural transformation of MLPOM accelerated by Hg(2+). Based on this discovery, MLPOM could be utilized as a colorimetric sensor to sense the existence of Hg(2+), and a simple and label-free method is developed to selectively detect aqueous Hg(2+). Furthermore, the colorimetric sensor has been applied to indicating mercury contamination in industrial sewage. PMID- 26559603 TI - [Otitis media with effusion in children younger than 1 year]. AB - OBJECTIVE: To determine the prevalence of otitis media with effusion in children younger than 1 year and its association with the season of the year, artificial feeding, environmental and perinatal factors. METHODS: Retrospective study of 184 randomly included medical records from a total of 982 healthy infants evaluated for hearing screening tests. Diagnosis of otitis media with effusion was based on otoscopy (amber-gold color, fluid level, handle of malleus position), type B tympanometric curves and absence of otoacoustic emissions. Incomplete medical records or those describing acute otitis media, upper respiratory tract infections on the assessment day or in the last 3 months, neuropathies and craniofacial anomalies were excluded. Data such as gestational age, birth weight, Apgar score, type of feeding and day care attendance were compared between children with and without otitis media with effusion through likelihood tests and multivariate analysis. RESULTS: 25.3% of 184 infants had otitis media with bilateral effusion; 9.2% had unilateral. In infants with otitis media, the following were observed: chronological age of 9.6+/-1.7 months; gestational age >38 weeks in 43.4% and birth weight >2,500g in 48.4%. Otitis media with effusion was associated with winter/fall, artificial feeding, Apgar score <7 and day care attendance. The multivariate analysis showed that artificial feeding is the factor most often associated to otitis media with effusion. CONCLUSIONS: Otitis media with effusion was found in about one third of children younger than 1 year and was mainly associated with artificial feeding. PMID- 26559604 TI - [Factors associated with short sleep duration in adolescents]. AB - OBJECTIVE: This study aimed to investigate the prevalence and factors associated with short sleep duration in adolescents from Maravilha - Santa Catarina (SC), southern Brazil. METHODS: The sample consisted of 516 adolescents aged 10-19 years of both genders. Issues associated with short sleep duration and difficulty falling asleep, chronotype, daytime sleepi-ness, physical activity, sedentary behavior and weight status were investigated. RESULTS: The prevalence of short sleep duration (<8h on school days) was 53.6%. Adolescents aged 17-19 years showed a 2.05-fold (95%CI: 1.20-3.50) greater prevalence of short sleep duration than those aged 10-12 years. The ones studying in morning and evening shifts had a higher prevalence of short sleep duration compared to those in the afternoon shift. Older age and school shift were the main factors associated with short sleep duration. CONCLUSIONS: Adolescents from Maravilha showed high prevalence of short sleep duration, and older adolescents that studied in the morning and evening shifts showed reduced sleep. PMID- 26559606 TI - A diagnostic tool for malaria based on computer software. AB - Nowadays, the gold standard method for malaria diagnosis is a staining of thick and thin blood film examined by expert laboratorists. It requires well-trained laboratorists, which is a time consuming task, and is un-automated protocol. For this study, Maladiag Software was developed to predict malaria infection in suspected malaria patients. The demographic data of patients, examination for malaria parasites, and complete blood count (CBC) profiles were analyzed. Binary logistic regression was used to create the equation for the malaria diagnosis. The diagnostic parameters of the equation were tested on 4,985 samples (703 infected and 4,282 control samples). The equation indicated 81.2% sensitivity and 80.3% specificity for predicting infection of malaria. The positive likelihood and negative likelihood ratio were 4.12 (95% CI = 4.01-4.23) and 0.23 (95% CI = 0.22-0.25), respectively. This parameter also had odds ratios (P value < 0.0001, OR = 17.6, 95% CI = 16.0-19.3). The equation can predict malaria infection after adjust for age, gender, nationality, monocyte (%), platelet count, neutrophil (%), lymphocyte (%), and the RBC count of patients. The diagnostic accuracy was 0.877 (Area under curve, AUC) (95% CI = 0.871-0.883). The system, when used in combination with other clinical and microscopy methods, might improve malaria diagnoses and enhance prompt treatment. PMID- 26559605 TI - [Identification of cutoff points for Homeostatic Model Assessment for Insulin Resistance index in adolescents: systematic review]. AB - OBJECTIVE: To identify cutoff points of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established for adolescents and discuss their applicability for the diagnosis of insulin resistance in Brazilian adolescents. DATA SOURCE: A systematic review was performed in the PubMed, Lilacs and SciELO databases, using the following descriptors: "Adolescents", "insulin resistance" and "ROC curve". Original articles carried out with adolescents published between 2005 and 2015 in Portuguese, English or Spanish languages, which included the statistical analysis using ROC curve to determine the index cutoff (HOMA-IR) were included. DATA SYNTHESIS: A total of 184 articles were identified and after the study phases were applied, seven articles were selected for the review. All selected studies established their cutoffs using a ROC curve, with the lowest observed cutoff of 1.65 for girls and 1.95 for boys and the highest of 3.82 for girls and 5.22 for boys. Of the studies analyzed, one proposed external validity, recommending the use of the HOMA-IR cutoff >2.5 for both genders. CONCLUSIONS: The HOMA-IR index constitutes a reliable method for the detection of insulin resistance in adolescents, as long as it uses cutoffs that are more adequate for the reality of the study population, allowing early diagnosis of insulin resistance and enabling multidisciplinary interventions aiming at health promotion of this population. PMID- 26559607 TI - Renal glomerular dysfunction in relation to retinal arteriolar narrowing and high pulse pressure in seniors. AB - Retinal arteriolar narrowing and high pulse pressure (PP) are associated with macrovascular complications and microvascular renal disease. Few studies addressed whether in seniors (?60 years) estimated glomerular filtration rate (eGFR) is independently related to central retinal arteriolar equivalent (CRAE) and PP. In 292 randomly recruited seniors (49.3% women; mean, 68.2 years), we measured PP by standard sphygmomanometry, CRAE (IVAN software), eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) and stage of chronic kidney disease (CKD (Kidney Disease Outcomes Quality Initiative guideline)). Statistical methods included linear and logistic regression. PP, CRAE and eGFR averaged 59.2 mm Hg, 146.3 MUm and 79.9 ml min(-1) per 1.73 m(2). Decline in eGFR (-2.27 ml min(-1) per 1.73 m(2) per 15 MUm; P=0.011) occurred in parallel with CRAE narrowing. CRAE (effect size per 1-s.d. increment, -1.85 MUm; P=0.032) and eGFR ( 2.68 ml min(-1) per 1.73 m(2); P=0.003) both declined with higher PP. With PP increasing from 63 to 73 mm Hg (threshold for macrovascular complications), CRAE dropped by -4.70 MUm (P?0.037). A 70-mm Hg PP threshold corresponded with a 150 MUm CRAE cutoff. The risk of CKD (stage ?2 vs. 1; n=203 vs. 89) rose with CRAE <150 MUm (odds ratio, 2.81; P<0.0001), but not with PP ?70 mm Hg (1.47; P=0.20). Additionally, CRAE added to PP increased the area under the curve from 0.58 to 0.64 (P=0.047) for identifying stage ?2 CKD. In seniors, CRAE and eGFR decline in parallel with higher PP. CRAE <150 MUm identifies early decline in eGFR. PMID- 26559608 TI - Exercise is a double-edged sword for endothelial function. PMID- 26559610 TI - Self-management of salt intake: clinical significance of urinary salt excretion estimated using a self-monitoring device. AB - Self-measured salt excretion from overnight urine samples shows significant correlation with 24-h-urinary salt excretion, but it is not known whether a self measuring method can monitor daily fluctuations in individual salt consumption. In this study, we measured salt excretion from 24-h urine samples (24-h salt) in 50 volunteers over 3 test days (2 weekdays and 1 holiday), and examined to what extent the values correlated with estimates of 24-h salt excretion from overnight urine samples obtained using a self-monitoring device (ON salt). Urine collection was considered successful when the difference between the predicted and actual 24 h-urinary creatinine excretion was within 30%. Thirty-three (M/F=7/26; 39.6+/ 16.7 years) out of 50 participants completed their urine collections successfully and their samples were used in the analysis. Twenty-four-hour salt and ON salt did not significantly differ between test days and between the weekdays and the holiday. Moreover, there was a significant positive correlation between 24-h salt and ON salt for each test day. The coefficients of variation (CVs) for 24-h salt among test days and among subjects were 24.7% and 21.3%, respectively. The CVs for ON salt were lower than those for 24-h salt (13.3% and 17.7%, respectively). In conclusion, self-measurement of salt excretion from overnight urine samples allows estimation of daily salt intake; thus, the use of a self-monitoring device may be a useful motivational tool for personal salt restriction. PMID- 26559609 TI - Association of body mass index and left ventricular mass index with abnormally low and high ankle-brachial indices in chronic kidney disease. AB - Obesity, left ventricular hypertrophy (LVH) and peripheral artery disease are frequently noted in patients with chronic kidney disease (CKD), thereby suggesting a close and causal relationship among them. This study was designed to assess whether the combination of an increased body mass index (BMI) and left ventricular mass index (LVMI) are independently associated with abnormally low and high ABI in patients with CKD stages 3-5. A total of 566 patients were included in the study and were classified into four groups according to sex specific median BMIs and LVMIs. The ABI was measured using an ABI-form device. Abnormally low and high ABI was defined as ABI <0.9 or ?1.3 in either leg. The combination of high BMI and LVMI (vs. the combination of low BMI and LVMI) was significantly associated with abnormally low and high ABI in an unadjusted model (odds ratio (OR), 2.107; P=0.015) and in a multivariable model after adjustment for demographic, clinical and biochemical characteristics and medications (OR, 4.219; P=0.008). In addition, the interaction between BMI and LVMI in abnormally low and high ABI was statistically significant in the unadjusted (OR, 1.002; P=0.001) and multivariate models (OR, 1.004; P=0.003). Our findings show that the combination of high BMI and LVMI was associated with abnormally low and high ABI in patients with CKD stages 3-5. Patients with high BMI and LVMI might be at a high risk of abnormally low and high ABI. PMID- 26559611 TI - Sequential Folding using Light-activated Polystyrene Sheet. AB - A pre-strained polystyrene (PS) polymer sheet is deformed when it approaches the glass transition state as a result of light absorption. By controlling the light absorption of the polymer sheet, non-contact sequential folding can be accomplished. Line patterns of different transparencies and shapes are used to control the light absorption. The line pattern shape is closely related to the folding angle and folding start time. The relation between the line pattern design and folding performance was evaluated experimentally to develop a technique for folding PS sheets. The results show that sequential folding of PS sheets can be accomplished by changing the degree of transparency of the line pattern. Using the technique developed in this study, self-folding origami structures with complicated shapes can be designed and manufactured. PMID- 26559612 TI - Layer-Resolved Cation Diffusion and Stoichiometry at the LaAlO3/SrTiO3 Heterointerface Probed by X-ray Photoemission Experiments and Site Occupancy Modeling. AB - The layer-resolved cation occupancy for different conducting and insulating interfaces of LaAlO3 (LAO) thin films on SrTiO3 (STO) has been determined by angle-resoled X-ray photoelectron spectroscopy (AR-XPS). Three STO interfaces with LAO have been considered, namely, a conducting interface with a 5 unit cell (u.c.) LAO layer, an insulating interface with a 5 u.c. LAO layer, and an insulating interface with a 3 u.c. LAO layer. Considering inelastic and elastic scattering processes in the transport approximation, the core-level signal attenuation has been modeled on the basis of Monte Carlo calculations of the electron trajectories across the heterostructures. Different effects involving cation stoichiometry and diffusion through the interface have been considered to interpret data. Beyond a mere abrupt interface modeling, the LaAlO3/SrTiO3 heterojunction is shown to host cation diffusion processes within 3-4 unit cells in the bulk layer, along with a clear Sr substoichiometry, an issue so far virtually neglected in the analysis of these systems. The present results show the capability of the AR-XPS modeling to explore element-sensitive properties at the oxide interfaces, matching and completing the information that can be provided by probes based on electron microscopy or X-ray scattering. PMID- 26559614 TI - Adaptation of microcystin thiol derivatization for matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis. AB - Thiol derivatization of microcystins is an emerging technique for simplifying mass spectrometric analysis of microcystins in complex matrices and for distinguishing between Mdha-/Dhb-containing microcystins. The present protocol is not compatible with MALDI-TOF mass spectrometry, but use of sodium carbonate buffer and desalting with ZipTips yielded no loss in sensitivity. Use of ammonium carbonate buffer followed by dilution in MALDI matrix resulted in a small loss of sensitivity but allowed accurate determination of reaction rates. PMID- 26559613 TI - The use of L-serine to prevent beta-methylamino-L-alanine (BMAA)-induced proteotoxic stress in vitro. AB - beta-methylamino-L-alanine (BMAA), a non-protein amino acid synthesised by cyanobacteria, has been linked to a complex neurological disorder on Guam and more recently to other cases of sporadic ALS (sALS), however the mechanisms of BMAA toxicity are not completely understood. We have previously demonstrated that BMAA is misincorporated into newly synthesised proteins by human neuroblastoma cells and fibroblasts, resulting in the formation of autofluorescent material and the induction of apoptotic cell death. In the present study we show that BMAA at low levels does not cause an acute toxicity in neuroblastoma cells but increases the expression of the ER stress marker, C/EBP homologous protein (CHOP) and increases the activity of the pro-apoptotic enzyme caspase-3. We also observed an increase in the activity of the lysosomal cysteine proteases cathepsin B and L, characteristic of the accumulation of proteins in the lysosomal system. We were able to prevent these proteotoxic effects in neuroblastoma cells through co treatment with l-serine suggesting that they resulted from incorporation of BMAA into proteins. Misincorporation provides a possible mechanism whereby BMAA could initiate misfolding, and the accumulation of aggregate-prone proteins in neurons. This build-up of misfolded proteins could explain the long latency period of the disease previously reported on Guam. PMID- 26559615 TI - In vivo exposure to northern diatoms arrests sea urchin embryonic development. AB - There are numerous reports indicating that marine diatoms may act harmful to early developmental stages of invertebrates. It is believed that the compounds responsible for these detrimental effects are oxylipins resulting from oxidized polyunsaturated fatty acids, and that they may function as grazing deterrents. Most studies reporting these effects have exposed test organisms to diatom extracts or purified toxins, but data from in vivo exposure to intact diatoms are scarce. We have conducted sea urchin egg incubation and plutei feeding experiments to test if intact diatom cells affected sea urchin embryo development and survival. This was done by exposing the common northern sea urchins Strongylocentrotus droebachiensis and Echinus acutus to northern strains of the diatoms Chaetoceros socialis, Skeletonema marinoi, Chaetoceros furcellatus, Attheya longicornis, Thalassiosira gravida and Porosira glacialis. The intact diatom cell suspensions were found to inhibit sea urchin egg hatching and embryogenesis. S. marinoi was the most potent one as it caused acute mortality in S. droebachiensis eggs after only four hours exposure to high (50 MUg/L Chla) diatom concentrations, as well as 24 h exposure to normal (20 MUg/L Chla) and high diatom concentrations. The second most potent species was T. gravida that caused acute mortality after 24 h exposure to both diatom concentrations. A. longicornis was the least harmful of the diatom species in terms of embryo development arrestment, and it was the species that was most actively ingested by S. droebachiensis plutei. PMID- 26559616 TI - Anterolateral adipofascial turnover flap of the leg: Anatomical study. AB - AIM: The aim of this study is to clearly define the vascularisation of the lateral paratibial septum of the leg, defining the basis for a vertical pedicled adipofascial flap harvested from the anterolateral aspect of the leg to cover pretibial soft tissue defects. MATERIALS AND METHODS: Twelve cadaver legs (eight fixed with formalin and four fresh) were dissected. The vessels running into the lateral paratibial septum were identified. The number of vessels were noted and evaluated at the lateral border of the proximal, middle and distal thirds of the leg. In addition, an angiographic study was performed on two limbs to confirm the connection between tibialis anterior artery and the overlaying fascia through these septal vessels. RESULTS: All the specimens had periosteo-septal vessels running in the lateral aspect of the tibia. The average number was 6.6. The distribution was constant in all the thirds of the leg. CONCLUSION: These data are useful to propose the harvesting technique for adipofascial flap with vertical pedicle as a suitable reconstructive option to cover pretibial soft tissue defects. PMID- 26559617 TI - Ultra-high-performance liquid chromatography-Time-of-flight high resolution mass spectrometry to quantify acidic drugs in wastewater. AB - A novel analytical approach involving an improved rotating-disk sorptive extraction (RDSE) procedure and ultra-high-performance liquid chromatography (UHPLC) coupled to an ultraspray electrospray ionization source (UESI) and time of-flight mass spectrometry (TOF/MS), in trap mode, was developed to identify and quantify four non-steroidal anti-inflammatory drugs (NSAIDs) (naproxen, ibuprofen, ketoprofen and diclofenac) and two anti-cholesterol drugs (ACDs) (clofibric acid and gemfibrozil) that are widely used and typically found in water samples. The method reduced the amount of both sample and reagents used and also the time required for the whole analysis, resulting in a reliable and green analytical strategy. The analytical eco-scale was calculated, showing that this methodology is an excellent green analysis, increasing its ecological worth. The detection limits (LOD) and precision (%RSD) were lower than 90ng/L and 10%, respectively. Matrix effects and recoveries were studied using samples from the influent of a wastewater treatment plant (WWTP). All the compounds exhibited suppression of their signals due to matrix effects, and the recoveries were approximately 100%. The applicability and reliability of this methodology were confirmed through the analysis of influent and effluent samples from a WWTP in Santiago, Chile, obtaining concentrations ranging from 1.1 to 20.5MUg/L and from 0.5 to 8.6MUg/L, respectively. PMID- 26559618 TI - Porous lead(II)-based metal organic nanotubes as an adsorbent for dispersive solid-phase extraction of polybrominated diphenyl ethers from environmental water samples. AB - Porous lead(II)-based metal-organic nanotubes (Pb-MONTs) were, for the first time, used as an adsorbent for dispersive solid-phase extraction (d-SPE) of polybrominated diphenyl ethers (PBDEs) at trace levels from environmental water samples. Gas chromatography-negative chemical ionization-mass spectrometry (GC NCI-MS) was applied for sample detection. Box-Behnken design was performed to investigate and optimize the d-SPE parameters through a response surface methodology. The optimized conditions were obtained as listed: extraction time of 1min, 51.4mg of adsorbent and NaCl concentration of 7.42%. Under the optimized conditions, the new d-SPE-GC-NCI-MS method achieved wide range of linearity (2 1000ngL(-1)), low limits of detection (0.08-0.22ngL(-1)), satisfactory repeatability (0.79-8.62%, n=6) and satisfactory reproducibility (3.18-11.0%, n=5), and the possible extraction mechanism was also discussed. The proposed method was used in the analysis of real environmental water samples, and satisfactory recoveries were obtained in the range of 80.5-119.2%. These results indicated that Pb-MONTs have great potential as an adsorbent for the d-SPE of PBDEs at trace levels from environmental water samples. PMID- 26559619 TI - Optimisation of temperature-programmed gas chromatographic separation of organochloride pesticides by response surface methodology. AB - A response surface methodology (RSM) approach is applied to optimise the temperature-programme gas-chromatographic separation of 16 organochloride pesticides, including 12 compounds identified as highly toxic chemicals by the Stockholm Convention on Persistent Organic Pollutants. A three-parameter relationship describing both linear and curve temperature programmes is derived adapting a model previously used in literature to describe concentration gradients in liquid chromatography with binary eluents. To investigate the influence of the three temperature profile descriptors (the starting temperature, the gradient duration and a shape parameter), a three-level full-factorial design of experiments is used to identify suitable combinations of the above variables spanning over a useful domain. Resolutions of adjacent peaks are the responses modelled by RSM using two alternative methods: a multi-layer artificial network (ANN) and usual polynomial regression. The proposed ANN-based approach permits to model simultaneously the resolutions of all the consecutive analyte pairs as a function of the temperature profile descriptors. Four critical pairs giving partially overlapped peaks are identified and multiresponse optimisation is carried out by analysing the surface plot of a global resolution defined as the average of the resolutions of the critical pairs. Descriptive/predictive performance and applicability of the ANN and polynomial RSM methods are compared and discussed. PMID- 26559621 TI - A coherent fiber link for very long baseline interferometry. AB - We realize a coherent fiber link for application in very long baseline interferometry (VLBI) for radio astronomy and geodesy. A 550-km optical fiber connects the Italian National Metrological Institute (INRIM) to a radio telescope in Italy and is used for the primary Cs fountain clock stability and accuracy dissemination. We use an ultrastable laser frequency- referenced to the primary standard as a transfer oscillator; at the radio telescope, an RF signal is generated from the laser by using an optical frequency comb. This scheme now provides the traceability of the local maser to the SI second, realized by the Cs fountain at the 1.7 * 10(-16) accuracy. The fiber link never limits the experiment and is robust enough to sustain radio astronomical campaigns. This experiment opens the possibility of replacing the local hydrogen masers at the VLBI sites with optically-synthesized RF signals. This could improve VLBI resolution by providing more accurate and stable frequency references and, in perspective, by enabling common- clock VLBI based on a network of telescopes connected by fiber links. PMID- 26559620 TI - Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons. AB - Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na(+) dependent K(+) (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations. PMID- 26559622 TI - A model and regularization scheme for ultrasonic beamforming clutter reduction. AB - Acoustic clutter produced by off-axis and multipath scattering is known to cause image degradation, and in some cases these sources may be the prime determinants of in vivo image quality. We have previously shown some success addressing these sources of image degradation by modeling the aperture domain signal from different sources of clutter, and then decomposing aperture domain data using the modeled sources. Our previous model had some shortcomings including model mismatch and failure to recover B-Mode speckle statistics. These shortcomings are addressed here by developing a better model and by using a general regularization approach appropriate for the model and data. We present results with L1 (lasso), L2 (ridge), and L1/L2 combined (elastic-net) regularization methods. We call our new method aperture domain model image reconstruction (ADMIRE). Our results demonstrate that ADMIRE with L1 regularization, or weighted toward L1 in the case of elastic-net regularization, have improved image quality. L1 by itself works well, but additional improvements are seen with elastic-net regularization over the pure L1 constraint. On in vivo example cases, L1 regularization showed mean contrast improvements of 4.6 and 6.8 dB on fundamental and harmonic images, respectively. Elastic net regularization (alpha = 0.9) showed mean contrast improvements of 17.8 dB on fundamental images and 11.8 dB on harmonic images. We also demonstrate that in uncluttered Field II simulations the decluttering algorithm produces the same contrast, contrast-tonoise ratio, and speckle SNR as normal B-mode imaging, demonstrating that ADMIRE preserves typical image features. PMID- 26559623 TI - Performance comparison of rigid and affine models for motion estimation using ultrasound radio-frequency signals. AB - Tissue motion estimation is widely used in many ultrasound techniques. Rigid model-based and nonrigid-modelbased methods are two main groups of space-domain methods of tissue motion estimation. The affine model is one of the commonly used nonrigid models. The performances of the rigid model and affine model have not been compared on ultrasound RF signals, which have been demonstrated to obtain higher accuracy, precision, and resolution in motion estimation compared with B mode images. In this study, three methods, i.e., the normalized cross-correlation method with rigid model (NCC), the optical flow method with rigid model (OFRM), and the optical flow method with affine model (OFAM), are compared using ultrasound RF signals, rather than the B-mode images used in previous studies. Simulations, phantom, and in vivo experiments are conducted to make the comparison. In the simulations, the root-mean-square errors (RMSEs) of axial and lateral displacements and strains are used to assess the accuracy of motion estimation, and the elastographic signal-tonoise ratio (SNRe) and contrast-to noise ratio (CNRe) are used to evaluate the quality of axial strain images. In the phantom experiments, the registration error between the pre- and postdeformation RF signals, as well as the SNRe and CNRe of axial strain images, are utilized as the evaluation criteria. In the in vivo experiments, the registration error is used to evaluate the estimation performance. The results show that the affinemodel- based method (i.e., OFAM) obtains the lowest RMSE or registration error and the highest SNRe and CNRe among all the methods. The affine model is demonstrated to be superior to the rigid model in motion estimation based on RF signals. PMID- 26559624 TI - Auto-focused virtual source imaging with arbitrarily shaped interfaces. AB - This work presents a new method, named auto-focused virtual source imaging (AVSI), for synthetic aperture focusing through arbitrarily shaped interfaces with arrays. First, the shape of the component surface is obtained by time-of flight (TOF) measurements. Then, a set of virtual source/receivers is created by focusing several array subapertures at the interface normal incidence points. Finally, the synthetic aperture focusing technique (SAFT) is applied to the received signals to generate a high-resolution image. The AVSI method provides several advantages for ultrasonic imaging in a two-media scenario. First, knowledge of the probe-part geometry is not required, because all information needed for image formation is obtained from a set of ultrasonic measurements. Second, refraction complications in TOF calculations are avoided, because foci at the interface can be considered as virtual source/ receivers, and SAFT can be performed in the second medium only. Third, the signal-to-noise ratio is higher than with synthetic aperture techniques that use a single element as emitter, and fourth, resolution is higher than that obtained by phased-array imaging with the same number of active elements, which reduces hardware complexity. The theoretical bases of the method are given, and its performance is evaluated by simulation. Finally, experimental results showing good agreement with theory are presented. PMID- 26559625 TI - High-power characterization of a microcutter actuated by PMN-PT piezocrystals. AB - An ultrasonic microcutter is an alternative approach to conventional ultrasonic instruments actuated by sandwich piezoelectric transducers for surgery. This paper reports high-power behavior of a microcutter actuated by the piezocrystal lead magnesium niobate-lead titanate (PMN-PT), defining its practical performance and the feasibility of PMNPT actuation for surgical applications. The microcutter was driven at resonance with constant current amplitudes, either unloaded or loaded by poultry breast tissue, until its behavior achieved a steady state. During this driving process, its electric impedance, resonant frequency, and vibration velocity, along with the temperature increase of the PMN-PT, were recorded in real time. The microcutter produced a maximum vibration velocity >2.8 m/s with an excitation current of 0.11 A(rms). The mechanical loss increased significantly with current amplitude, resulting in a maximum temperature increase approaching 50 degrees C around the interface between the PMN-PT and the blade, where they were bonded together with epoxy. Because of the low phase-transition temperature of PMN-PT, this temperature rise prevented the microcutter from working at higher current amplitudes. Along with the high vibration velocity, it also caused a frequency shift downward by 3 kHz at the same current amplitude. During tests with poultry breast tissue, radiation reactance increased the resonant frequency and the radiation resistance increased the loss of the microcutter. However, the loss did not further increase the temperature of the piezoelectric material. The maximum force and the overall work required to penetrate the microcutter into poultry breast tissue were reduced by 47.1 +/- 8% and 53.5 +/- 6%, respectively, when the microcutter was actuated at a current of 0.07 A(rms). PMID- 26559626 TI - Ultrasonic scattering measurements of a live single cell at 86 MHz. AB - Cell separation and sorting techniques have been employed biomedical applications such as cancer diagnosis and cell gene expression analysis. The capability to accurately measure ultrasonic scattering properties from cells is crucial in making an ultrasonic cell sorter a reality if ultrasound scattering is to be used as the sensing mechanism as well. To assess the performance of sensing and identifying live single cells with high-frequency ultrasound, an 86-MHz lithium niobate press-focused single-element acoustic transducer was used in a high frequency ultrasound scattering measurement system that was custom designed and developed for minimizing noise and allowing better mobility. Peak-to-peak echo amplitude, integrated backscatter (IB) coefficient, spectral parameters including spectral slope and intercept, and midband fit from spectral analysis of the backscattered echoes were measured and calculated from a live single cell of two different types on an agar surface: leukemia cells (K562 cells) and red blood cells (RBCs). The amplitudes of echo signals from K562 cells and RBCs were 48.25 +/- 11.98 mV(pp) and 56.97 +/- 7.53 mV(pp), respectively. The IB coefficient was 89.39 +/- 2.44 dB for K562 cells and -89.00 +/- 1.19 dB for RBCs. The spectral slope and intercept were 0.30 +/- 0.19 dB/MHz and -56.07 +/- 17.17 dB, respectively, for K562 cells and 0.78 +/- 0.092 dB/MHz and -98.18 +/- 8.80 dB, respectively, for RBCs. Midband fits of K562 cells and RBCs were -31.02 +/- 3.04 dB and -33.51 +/- 1.55 dB, respectively. Acoustic cellular discrimination via these parameters was tested by Student's t-test. Their values, except for the IB value, showed statistically significant difference (p < 0.001). This paper reports for the first time that ultrasonic scattering measurements can be made on a live single cell with a highly focused high-frequency ultrasound microbeam at 86 MHz. These results also suggest the feasibility of ultrasonic scattering as a sensing mechanism in the development of ultrasonic cell sorters. PMID- 26559627 TI - Modeling of wave propagation for medical ultrasound: a review. AB - Numerical modeling of medical ultrasound has advanced tremendously in the past two decades. This opens up a great number of opportunities for medical ultrasound and associated technologies. Numerous new governing equations and algorithms have emerged and been applied to studying various medical ultrasound applications, including ultrasound imaging, photo-acoustic imaging, and therapeutic ultrasound. In addition, thanks to the rapid development of computers, modeling acoustic wave propagation in three-dimensional, large-scale domains has become a reality. This article will provide an indepth literature and technical review of recent progress on numerical modeling of medical ultrasound. Future challenges will also be discussed. PMID- 26559628 TI - Highly piezoelectric MgZr co-doped aluminum nitride-based vibrational energy harvesters. AB - The first MgZr co-doped AlN-based vibrational energy harvester (VEH) is presented. (MgZr)AlN, which is a new class of doped AlN, provides high piezoelectricity and cost advantage. Using 13%-(MgZr)-doped AlN for micromachined VEHs, maximum output power of 1.3 MUW was achieved with a Q-factor of 400 when resonant frequency, vibration acceleration, load resistance were 792 Hz, 8 m/s(2), and 1.1 MOmega, respectively. Normalized power density was 8.1 kW.g( 2).m(-3). This was one of the highest values among the currently available piezoelectric VEHs. PMID- 26559629 TI - Evaluation of the transverse oscillation method using the Cramer-Rao lower bound. AB - The transverse oscillation method enables lateral displacement tracking by generating an oscillation orthogonal to the conventional RF signal. The widely varying methods used in the field to create such oscillations and perform displacement estimation make it difficult to compare the expected performance of alternative techniques. We derive closed-form expressions for the oscillating pressure fields produced by two common apodization functions-the rectangular and bi-lobed Gaussian apodizations-after heterodyning demodulation is applied to separate the orthogonally-oscillating signals. With these fields and spectra we present a form of the Cramer-Rao lower bound for ultrasonic signals that contains a spectrum shape term, allowing theoretical prediction of relative performance across different techniques and parameter choices. Simulations show good agreement with the trends predicted by the theoretical results for the chosen class of aperture functions. The simulations demonstrate the importance of frequency-space analysis in devising a transverse oscillation scheme and suggest that the study of other classes of aperture functions and field formation techniques should be continued to further improve the accuracy of lateral displacement tracking. PMID- 26559630 TI - The angular apodization in coherent plane-wave compounding. AB - This article describes the relation between apodization in conventional focused imaging and apodization in coherent plane-wave compounding (CPWC). We pose the hypothesis that equivalent transmit beams can be produced with both methods if the transmit apodization is adequately transformed. We derive a relation between apodization in CPWC and in synthetic transmit aperture imaging (STAI), which we argue to be equivalent to conventional optimal multifocus imaging. We find that under certain conditions, the transformation of the apodization becomes trivial and the same window used in STAI can be applied for CPWC but extended to the whole angle sequence. We test the hypothesis with in silico data and find that the transformed apodization accurately mimics the objective transmit apodization, with differences in the lateral resolution between 3% and 6%. PMID- 26559631 TI - Erratum: Effect of element directivity on adaptive beamforming applied to high frame-rate ultrasound. PMID- 26559633 TI - Ulcerative Pretibial Lesions in the Setting of Multifactorial Immunosuppression. PMID- 26559634 TI - The cervix as a natural tamponade in postpartum hemorrhage caused by placenta previa and placenta previa accreta: a prospective study. AB - BACKGROUND: Placenta previa and placenta accreta carry significant maternal and fetal morbidity and mortality. Several techniques have been described in the literature for controlling massive bleeding associated with placenta previa cesarean sections. The objective of this study was to evaluate the efficacy and safety of the use of the cervix as a natural tamponade in controlling postpartum hemorrhage caused by placenta previa and placenta previa accreta. METHODS: This prospective study was conducted on 40 pregnant women admitted to our hospital between June 2012 and November 2014. All participating women had one or more previous cesarean deliveries and were diagnosed with placenta previa and/or placenta previa accreta. Significant bleeding from the placental bed during cesarean section was managed by inverting the cervix into the uterine cavity and suturing the anterior and/or the posterior cervical lips into the anterior and/or posterior walls of the lower uterine segment. RESULTS: The technique of cervical inversion described above was successful in stopping the bleeding in 38 out of 40 patients; yielding a success rate of 95%. We resorted to hysterectomy in only two cases (5%). The mean intra-operative blood loss was 1572.5 mL, and the mean number of blood units transfused was 3.1. The mean time needed to perform the technique was 5.4 +/- 0.6 min. The complications encountered were as follows: bladder injury in the two patients who underwent hysterectomy and wound infection in one patient. Postoperative fever that responded to antibiotics occurred in 1 patient. The mean duration of the postoperative hospital stay was 3.5 days CONCLUSIONS: This technique of using the cervix as a natural tamponade appears to be safe, simple, time-saving and potentially effective method for controlling the severe postpartum hemorrhage (PPH) caused by placenta previa/placenta previa accreta. This technique deserves to be one of the tools in the hands of obstetricians who face the life-threatening hemorrhage of placenta accreta. TRIAL REGISTRATION: ClinicalTrials.gov NCT02590484 . Registered 28 October 2015. PMID- 26559632 TI - Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy. AB - BACKGROUND: Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. RESULTS: A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. CONCLUSIONS: Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART. PMID- 26559635 TI - Validation of the German version of the STarT-Back Tool (STarT-G): a cohort study with patients from primary care practices. AB - BACKGROUND: Current research emphasizes the high prevalence and costs of low back pain (LBP). The STarT Back Tool was designed to support primary care decision making for treatment by helping to determine the treatment prognosis of patients with non-specific low back pain. The German version is the STarT-G. The cross cultural translation of the tool followed a structured and widely accepted process but to date it was only partially validated with a small sample. The aim of the study was to test the psychometric properties construct validity, discriminative ability, internal consistency and test-retest-reliability of the STarT-G and to compare them with values given for the original English version. METHODS: A consecutive cohort study with a two-week retest was conducted among patients with non-specific LBP, aged 18 to 60 years, from primary care practices. Questionnaires were collected before the first consultation, and two weeks later by post, using the following reference standards: the Roland and Morris disability questionnaire, the Tampa Scale of Kinesiophobia, the Pain Catastrophizing Scale and the Hospital Anxiety and Depression Scale. Psychometric properties examined included the tool's discriminative abilities, whether the psychosocial subscale was one factor, internal consistency, item redundancy, test retest reliability and floor and ceiling effects. RESULTS: There were 228 patients recruited with a mean age of 42.2 (SD 11.0) years, and 53 % were female. The areas under the curve (AUC) for discriminative ability ranged from 0.70 (STarT-G Subscale - Pain Catastrophizing Scale; CI95 0.63, 0.78) to 0.77 (STarT-G Total - Composite reference standard, CI95 0.60, 0.94). Factor loadings ranged from 0.49 to 0.74. Cronbach's alpha testing the internal consistency and redundancy for the total/subscale scores were alpha = 0.52/0.55 respectively. The STarT-G test-retest reliability Kappa values for the total/subscale scores were 0.67/0.68 respectively. No floor or ceiling effects were present. CONCLUSIONS: The STarT-G shows acceptable psychometric properties although not in exact agreement with the original English version. The items previously regarded as a psychosocial subscale may be better seen as an index of different individual psychosocial constructs. The relevance of using the tool at the point of consultation should be further examined. PMID- 26559636 TI - Mealybug species from Chilean agricultural landscapes and main factors influencing the genetic structure of Pseudococcus viburni. AB - The present study aimed to characterize the distribution of mealybug species along Chilean agro-ecosystems and to determine the relative impact of host plant, management strategy, geography and micro-environment on shaping the distribution and genetic structure of the obscure mealybug Pseudococcus viburni. An extensive survey was completed using DNA barcoding methods to identify Chilean mealybugs to the species level. Moreover, a fine-scale study of Ps. viburni genetic diversity and population structure was carried out, genotyping 529 Ps. viburni individuals with 21 microsatellite markers. Samples from 16 localities were analyzed using Bayesian and spatially-explicit methods and the genetic dataset was confronted to host-plant, management and environmental data. Chilean crops were found to be infested by Ps. viburni, Pseudococcus meridionalis, Pseudococcus longispinus and Planococcus citri, with Ps. viburni and Ps. meridionalis showing contrasting distribution and host-plant preference patterns. Ps. viburni samples presented low genetic diversity levels but high genetic differentiation. While no significant genetic variance could be assigned to host-plant or management strategy, climate and geography were found to correlate significantly with genetic differentiation levels. The genetic characterization of Ps. viburni within Chile will contribute to future studies tracing back the origin and improving the management of this worldwide invader. PMID- 26559637 TI - Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. AB - BACKGROUND: Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. AIM: To verify the non inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy. METHODS: In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A-D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks. RESULTS: Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long-term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well-tolerated. CONCLUSIONS: The non-inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well tolerated and effective during the long-term maintenance study. PMID- 26559638 TI - The Victorian Melanoma Service: A 20-year review of an Australian multidisciplinary cancer service. AB - Australia has the highest incidence and mortality rates for melanoma in the world. The Victorian Melanoma Service began operation in 1994 as one of the first multidisciplinary melanoma clinics in Victoria. We conducted a review of the Victorian Melanoma Service database of 6721 patients and present the trends observed in a statewide referral centre in Australia. Our results highlight the importance of multidisciplinary care of melanoma patients and emphasise the significance of histological reviews and dermatological skin assessments for the detection of synchronous melanoma. PMID- 26559639 TI - Which direction should Australian health system reform be heading? PMID- 26559640 TI - Automated amplicon design suitable for analysis of DNA variants by melting techniques. AB - BACKGROUND: The technological development of DNA analysis has had tremendous development in recent years, and the present deep sequencing techniques present unprecedented opportunities for detailed and high-throughput DNA variant detection. Although DNA sequencing has had an exponential decrease in cost per base pair analyzed, focused and target-specific methods are however still much in use for analysis of DNA variants. With increasing capacity in the analytical procedures, an equal demand in automated amplicon and primer design has emerged. RESULTS: We have constructed a web-based tool that is able to batch design DNA variant assay suitable for analysis by denaturing gel/capillary electrophoresis and high resolution melting. The tool is developed as a computational workflow that implements one of the most widely used primer design tools, followed by validation of primer specificity, as well as calculation and visualization of the melting properties of the resulting amplicon, with or without an artificial high melting domain attached. The tool will be useful for scientists applying DNA melting techniques in analysis of DNA variations. The tool is freely available at http://meltprimer.ous-research.no/ . CONCLUSION: Herein, we demonstrate a novel tool with respect to covering the whole amplicon design workflow necessary for groups that use melting equilibrium techniques to separate DNA variants. PMID- 26559641 TI - Tick exposure and extreme climate events impact survival and threaten the persistence of a long-lived lizard. AB - Assessing the impacts of multiple, often synergistic, stressors on the population dynamics of long-lived species is becoming increasingly important due to recent and future global change. Tiliqua rugosa (sleepy lizard) is a long-lived skink (>30 years) that is adapted to survive in semi-arid environments with varying levels of parasite exposure and highly seasonal food availability. We used an exhaustive database of 30 years of capture-mark-recapture records to quantify the impacts of both parasite exposure and environmental conditions on the lizard's survival rates and long-term population dynamics. Lizard abundance was relatively stable throughout the study period; however, there were changing patterns in adult and juvenile apparent survival rates, driven by spatial and temporal variation in levels of tick exposure and temporal variation in environmental conditions. Extreme weather events during the winter and spring seasons were identified as important environmental drivers of survival. Climate models predict a dramatic increase in the frequency of extreme hot and dry winter and spring seasons in our South Australian study region; from a contemporary probability of 0.17 up to 0.47-0.83 in 2080 depending on the emissions scenario. Our stochastic population model projections showed that these future climatic conditions will induce a decline in the abundance of this long-lived reptile of up to 67% within 30 years from 2080, under worst case scenario modelling. The results have broad implications for future work investigating the drivers of population dynamics and persistence. We highlight the importance of long-term data sets and accounting for synergistic impacts between multiple stressors. We show that predicted increases in the frequency of extreme climate events have the potential to considerably and negatively influence a long-lived species, which might previously have been assumed to be resilient to environmental perturbations. PMID- 26559642 TI - Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells. AB - Glioblastoma (GBM) generally exhibits high IC50 values for its standard drug treatment, temozolomide (TMZ). MicroRNA-21 (miR-21) is an oncomiR overexpressed in GBM, thus controlling important aspects of glioma biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 to glioblastoma cells might beneficially knock down endogenous miR-21 prior to TMZ treatment. PLGA nanoparticles encapsulating antisense miR-21 were effective in intracellular delivery and sustained silencing (p < 0.01) of miR-21 function in U87 MG, LN229, and T98G cells. Prior antisense miR-21 delivery significantly reduced the number of viable cells (p < 0.001), and increased (1.6-fold) cell cycle arrest at G2/M phase upon TMZ treatment in U87 MG cells. There was overexpression of the miR-21 target genes PTEN (by 67%) and caspase-3 (by 15%) upon cotreatment. This promising PLGA nanoparticle-based platform for antisense miR-21 delivery to GBM is an effective cotherapeutic strategy in cell culture, warranting the need for further studies prior to future clinical translation. PMID- 26559643 TI - Structured intervention for management of pain following day surgery in children. AB - BACKGROUND: Ambulatory surgery forms a large part of pediatric surgical practice. Several studies indicate that postoperative pain is poorly managed with more than 30% of children having moderate to severe pain. In a busy outpatient clinic contact between healthcare professionals and the family is increasingly limited calling for a global and efficient pain management regime. OBJECTIVE: The aim of this prospective observational cohort study was to determine postoperative pain intensity following day surgery in children after our structured intervention for pain management. METHODS: A number of interventions in an effort to address barriers to effective postoperative pain management after day surgery were identified in the literature. By introducing our concept structured intervention, we aimed to address the majority if not all these barriers. Accordingly, we adapted postoperative pain management to each child using a multimodal approach consisting of surgery-specific analgesia with weight appropriate doses of acetaminophen and ibuprofen. Analgesics were handed out to the parents in formulations accepted by child and parent and after thorough information to the parents. RESULTS: Two hundred and forty-five children were scheduled for surgery during the 3-month period of which 149 children were available for analysis. The postoperative pain as assessed by the parents with a the Short Form of the Parents' Postoperative Pain Measure (PPPM-SF) was well managed exhibiting a median pain score of 4 on postoperative day 0 (POD0) and median 1 on postoperative day 1 (POD1) and a numeric rating scale (NRS) median pain score of 2 on POD0 and median 1 on POD1. We found a highly significant correlation between the PPPM-SF and the NRS scores. CONCLUSION: After thorough information of the parents we have successfully implemented a surgery-specific regime of primarily around-the-clock dosing of drug formulations acceptable for the specific child with dispensed medication ready available for the family. PMID- 26559644 TI - Feasibility of surgeon-performed ultrasound-guided core needle biopsy in the thyroid and lymph nodes. AB - BACKGROUND: The purpose of this study was to evaluate the feasibility of ultrasound-guided core needle biopsy (CNB) performed by a surgeon for mass lesions in the thyroid and lymph nodes. METHODS: A single surgeon performed 30 office-based ultrasound-guided CNB procedures for mass lesions in the thyroid and lymph nodes that were previously biopsied by ultrasound-guided fine-needle aspiration cytology (FNAC). The procedure time, targeting success, pathological diagnosis, and complications were evaluated. RESULTS: The mean procedure time for ultrasound-guided CNB was 6.7 minutes, and it reached a plateau of 4 to 7 minutes after the first 5 procedures. The overall unsatisfactory sampling rate was 3.3% (1 of 30). Specific pathological diagnoses that permitted the surgeon to establish an appropriate treatment plan were provided in 93.3% of the patients (28 of 30). There were no major complications. CONCLUSION: Ultrasound-guided CNB is technically feasible for a head and neck surgeon and a useful adjunct technique when ultrasound-guided FNAC is inadequate for mass lesions in the thyroid and lymph nodes. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1413 E1418, 2016. PMID- 26559645 TI - Thermostilla marina gen. nov., sp. nov., a thermophilic, facultatively anaerobic planctomycete isolated from a shallow submarine hydrothermal vent. AB - A novel thermophilic planctomycete (strain SVX8T) was isolated from a shallow submarine hydrothermal vent, Vulcano Island, Italy. The temperature range for growth was 30-68 degrees C, with an optimum at 55 degrees C. The pH range for growth was 5.0-9.0, with an optimum at pH 7.0-8.0. Growth was observed at NaCl concentrations ranging from 0.8 to 4.5 % (w/v) with an optimum at 2.5-3.5 % (w/v). The isolate grew anaerobically using a number of mono-, di- and polysaccharides as electron donors and nitrate or elemental sulfur as electron acceptors or by fermentation. Nitrate was reduced to nitrite; sulfur was reduced to sulfide. Strain SVX8T did not grow at atmospheric concentration of oxygen but grew microaerobically (up to 2 % oxygen in the gas phase). The G+C content of the DNA of strain SVX8T was 58.5 mol%. Based on phylogenetic position and phenotypic features, the new isolate is considered to represent a novel species belonging to a new genus in the order Planctomycetales, for which the name Thermostilla marina gen. nov., sp. nov. is proposed. The type strain of Thermostilla marina is SVX8T ( = JCM 19992T = VKM B-2881T). Strain SVX8T is the first thermophilic planctomycete isolated from a marine environment. PMID- 26559646 TI - The Role of Sensorimotor Incongruence in Pain in Professional Dancers. AB - This study evaluated whether dancers with pain experience more sensory changes during an experimentally induced sensorimotor incongruent task and explored the relationship between sensorimotor incongruence and self-reported measures (e.g., Short Form 36-questionnaire (SF-36), psychosocial variables and physical activity). Forty-four dancers were subjected to a bimanual coordination test simulating sensorimotor incongruence (i.e., performing congruent and incongruent arm movements while viewing a whiteboard or mirror) and completed standardized questionnaires. Significantly more dancers experienced sensory changes during the performance of incongruent movements while viewing a mirror (p < .01), but the intensity of the reported sensations was very low. No differences were observed between dancers with and without baseline pain, but significant negative associations were found between sensorimotor incongruence and subscores of the SF 36. Sensorimotor incongruence can provoke small sensory changes in dancers but appears unrelated to baseline pain symptoms. Sensorimotor incongruence appears to be related to quality of life. PMID- 26559647 TI - Pink Noise in Rowing Ergometer Performance and the Role of Skill Level. AB - The aim of this study was to examine (1) the temporal structures of variation in rowers' (natural) ergometer strokes to make inferences about the underlying motor organization, and (2) the relation between these temporal structures and skill level. Four high-skilled and five lower-skilled rowers completed 550 strokes on a rowing ergometer. Detrended Fluctuation Analysis was used to quantify the temporal structure of the intervals between force peaks. Results showed that the temporal structure differed from random, and revealed prominent patterns of pink noise for each rower. Furthermore, the high-skilled rowers demonstrated more pink noise than the lower-skilled rowers. The presence of pink noise suggeststhat rowing performance emerges from the coordination among interacting component processes across multiple time scales. The difference in noise pattern between high-skilled and lower-skilled athletes indicates that the complexity of athletes' motor organization is a potential key characteristic of elite performance. PMID- 26559648 TI - Reconstruction of Large Cheek Defect With/Without Sideburn Using Malar-Posterior Auricular-Cervico Flap. AB - The cheek region is the most common site for malignant tumor occurrence and the treatment of malignant skin tumor requires extensive local excision. Many previous reports have covered methods of reconstruction using local flaps for skin defects in the cheek region.In this article, we describe our experience with a surgical reconstruction using a new flap method for 8 patients with missing tissue in the cheek region. This flap is based on the concept of separately designing the flap with the 3 areas comprising the malar, posterior auricular, and cervical regions. We named the flap containing these 3 regions the malar posterior auricular-cervico flap. Esthetically satisfactory outcomes were achieved in all cases.In conclusion, we recommend our malar-posterior auricular cervico flap to reconstruct the tissue defects of approximately 20 to 40 cm after tumor excision in the cheek region. If preauricular skin is included in the design of this flap, the sideburn can be reconstructed using a part of the nape region with hair. PMID- 26559650 TI - Atypical chorioretinal coloboma in a Golden Retriever: a retinographic, fluoroangiographic, and optical coherence tomography study. AB - PURPOSE: To report a case of canine atypical chorioretinal coloboma where ophthalmoscopic, fluoroangiographic and optical coherence tomography characteristics are described. ANIMAL STUDIED: A 2-year-old Golden Retriever dog in which routine ophthalmoscopic examination allowed diagnosis of a posterior coloboma on the left eye. PROCEDURES: Retinography, fluorescein angiography, and optical coherence tomography were performed to characterize the lesion of the left fundus. RESULTS: Ophthalmoscopy revealed a pigmented circumscribed lesion dorsal to the optic nerve of the left fundus, surrounded by small areas of hyper reflectivity and retinal vessels with an abnormal pattern. Fluoroangiography revealed a constant hypofluorescence of the defect and a complete altered vascular pattern associated with the coloboma. Optical coherence study demonstrated an important craterlike depression showing an atrophic neurosensory retina, and a lack of retinal pigment epithelium and choroidal tissue. CONCLUSIONS: Fluoroangiographic and optical coherence tomographic studies of an atypical chorioretinal coloboma in a dog are reported for the first time. Both imaging techniques are of great importance to characterize this type of congenital defects. PMID- 26559649 TI - Outcomes After Combined Radical Resection and Targeted Biologic Therapy for the Management of Recalcitrant Hidradenitis Suppurativa. AB - BACKGROUND: Trials demonstrating the efficacy of biologic therapy for moderate to severe hidradenitis suppurativa (HS) have inspired new multidisciplinary treatment strategies. We present our experience with combined biologic and surgical therapy for recalcitrant HS. METHODS: Between 2011 and 2014, 21 patients (57 cases) with Hurley Stage III HS underwent radical resection with delayed primary closure alone, or in combination with adjuvant biologic therapy. Demographic data, treatment regimen, outcomes, and complications were retrospectively reviewed for all cases. RESULTS: Eleven patients underwent combined surgical and biologic therapy, whereas radical resection alone was performed in 10 patients. The average soft tissue deficit, before closure, for the combined and surgery-only patients was 56 cm and 48.5 cm, respectively (P = 0.66). Biologic agents including infliximab (n = 8) and ustekinumab (n = 3) were initiated 2 to 3 weeks after closure and were continued for an average of 10.5 months. Recurrence was noted in 19% (4/29) and 38.5% (10/26) of previously treated sites for combined and surgery-only patients (P < 0.01). For the combined cohort, the disease-free interval was approximately 1 year longer on average (P < 0.001); however, this difference was reduced to 4.5 months when considering time to recurrence after cessation of biologic therapy (P = 0.09). New disease developed in 18% (2/11) and 50% (5/10) of combined and surgery-only patients, respectively (P < 001). No adverse events were noted among patients who received biologic therapy. CONCLUSIONS: Lower rates of recurrence and disease progression, as well as a longer disease-free interval may be achieved with the use of adjuvant biologic therapy after radical resection for recalcitrant HS. PMID- 26559651 TI - Hypervalent Activation as a Key Step for Dehydrogenative ortho C-C Coupling of Iodoarenes. AB - Building on earlier results, a direct metal-free alpha-arylation of substituted cyclic 1,3-diones using ArI(O2CCF3)2 reagents has been developed; unlike other arylative approaches, the arylated products retain the iodine substituent ortho to the newly formed C-C bond. The mechanism is explored by using DFT calculations, which show a vanishingly small activation barrier for the C-C bond forming step. In fact, taking advantage of an efficient in situ hypervalent activation, the iodoarenes are shown to undergo a cross-dehydrogenative C-C coupling at the C-H ortho to the iodine. When Oxone is used as terminal oxidant, the process is found to benefit from a rapid initial formation of the hypervalent ArI(OR)2 species and the sulfate-accelerated final coupling with a ketone. This method complements the ipso selectivity obtained in the metal-catalyzed alpha arylation of carbonyl compounds. PMID- 26559652 TI - Erectile Dysfunction and Mortality in a National Prospective Cohort Study. AB - INTRODUCTION: Emerging work has shown erectile dysfunction (ED) to be an important indicator of cardiovascular risk via its shared pathophysiology. Yet limited research has examined if a direct relationship between ED and mortality risk exists. AIM: The purpose of this brief report was to better define the relationship between ED and mortality risk. METHODS: Prevalent ED was assessed with the question: "How would you describe your ability to get and keep an erection adequate for satisfactory intercourse?" Participant data from the population-based 2003-2004 National Health and Nutrition Examination Survey (NHANES) was linked to death certificates from the National Death Index for mortality assessment. MAIN OUTCOME MEASURES: Increased risk of premature all cause mortality among those with ED (vs. those without). RESULTS: Of 1,790 adult men providing complete data (age range: 20-85 years; mean = 45.4 year), with 557 having ED, over a 93-month follow-up, 244 deceased over this time. After adjustments, those with ED (vs. those without) had a 70% increased risk of premature all-cause mortality (hazards ratio = 1.70; 95% confidence interval; 1.01-2.85; P = 0.04). CONCLUSIONS: ED is associated with increased premature mortality risk. The present findings have major public health and clinical implications in that ED is a strong indicator of premature mortality. Therefore, patients with ED should be screened and possibly treated for complications that may increase the risk of premature death. PMID- 26559653 TI - Synthesis, Structure, and Reactivity of the Ethyl Yttrium Metallocene, (C5Me5)2Y(CH2CH3), Including Activation of Methane. AB - (C5Me5)2Y(MU-Ph)2BPh2, 1, reacted with ethyllithium at -15 degrees C to make (C5Me5)2Y(CH2CH3), 2, which is thermally unstable at room temperature and formed the C-H bond activation product, (C5Me5)2Y(MU-H)(MU-eta(1):eta(5) CH2C5Me4)Y(C5Me5), 3, containing a metalated (C5Me5)(1-) ligand. Spectroscopic evidence for 2 was obtained at low temperature, and trapping experiments with (i)PrNCN(i)Pr and CO2 gave the Y-CH2CH3 insertion products, (C5Me5)2Y[(i)PrNC(Et)N(i)Pr-kappa(2)N,N'], 4, and [(C5Me5)2Y(MU-O2CEt)]2, 5. Although 2 is highly reactive, low temperature isolation methods allowed the isolation of single crystals which revealed an 82.6(2) degrees Y-CH2-CH3 bond angle consistent with an agostic structure in the solid state. Complex 2 reacted with benzene and toluene to make (C5Me5)2YPh, 7, and (C5Me5)2YCH2Ph, 8, respectively. The reaction of 2 with [(C5Me5)2YCl]2 formed (C5Me5)2Y(MU-Cl)(MU eta(1):eta(5)-CH2C5Me4)Y(C5Me5) in which a (C5Me5)(1-) ligand was metalated. C-H bond activation also occurred with methane which reacted with 2 to make [(C5Me5)2YMe]2, 9. PMID- 26559654 TI - Not All Inner Ears are the Same: Otolith Matrix Proteins in the Inner Ear of Sub Adult Cichlid Fish, Oreochromis Mossambicus, Reveal Insights Into the Biomineralization Process. AB - The fish ear stones (otoliths) consist mainly of calcium carbonate and have lower amounts of a proteinous matrix. This matrix consists of macromolecules, which directly control the biomineralization process. We analyzed the composition of this proteinous matrix by mass spectrometry in a shotgun approach. For this purpose, an enhanced protein purification technique was developed that excludes any potential contamination of proteins from body fluids. Using this method we identified eight proteins in the inner ear of Oreochromis mossambicus. These include the common otolith matrix proteins (OMP-1, otolin-1, neuroserpin, SPARC and otoconin), and three proteins (alpha tectorin, otogelin and transferrin) not previously localized to the otoliths. Moreover, we were able to exclude the occurrence of two matrix proteins (starmaker and pre-cerebellin-like protein) known from other fish species. In further analyses, we show that the absence of the OMP starmaker corresponds to calcitic otoliths and that pre-cerebellin-like protein is not present at any stage during the development of the otoliths of the inner ear. This study shows O. mossambicus does not have all of the known otolith proteins indicating that the matrix proteins in the inner ear of fish are not the same across species. Further functional studies of the novel proteins we identified during otolith development are required. PMID- 26559655 TI - Emerging methodologies for pathogen identification in positive blood culture testing. AB - Bloodstream infections (BSIs) represent a major cause of death in developed countries and are associated with long-term loss of functions. Blood culture remains the gold standard for BSI diagnosis, as it is easy to perform and displays a good analytical sensitivity. However, its major drawback remains the long turnaround time, which can result in inappropriate therapy, fall of survival rate, emergence of antibiotic resistance and increase of medical costs. Over the last 10 years, molecular tools have been the alternative to blood cultures, allowing early identification of pathogens involved in sepsis, as well detection of critical antibiotic resistance genes. Besides, the advent of MALDI-TOF revolutionized practice in routine microbiology significantly reduced the time to result. Reviewed here are recent improvements in early BSI diagnosis and these authors' view for the future is presented, including innovative high-throughput technologies. PMID- 26559656 TI - Probing 2D black phosphorus by quantum capacitance measurements. AB - Two-dimensional materials and their heterostructures have emerged as a new class of materials, not only for fundamental physics but also for electronic and optoelectronic applications. Black phosphorus (BP) is a relatively new addition to this class of materials. Its strong in-plane anisotropy makes BP a unique material for making conceptually new types of electronic devices. However, the global density of states (DOS) of BP in device geometry has not been measured experimentally. Here, we report the quantum capacitance measurements together with the conductance measurements on an hBN-protected few-layer BP (~six layers) in a dual-gated field effect transistor (FET) geometry. The measured DOS from our quantum capacitance is compared with density functional theory (DFT). Our results reveal that the transport gap for quantum capacitance is smaller than that in conductance measurements due to the presence of localized states near the band edge. The presence of localized states is confirmed by the variable range hopping seen in our temperature dependence conductivity. A large asymmetry is observed between the electron and hole side. This asymmetric nature is attributed to the anisotropic band dispersion of BP. Our measurements establish the uniqueness of quantum capacitance in probing the localized states near the band edge, hitherto not seen in conductance measurements. PMID- 26559657 TI - Predictive wear modeling of the articulating metal-on-metal hip replacements. AB - The lubrication regime in which artificial hip joints operate adds complexity to the prediction of wear, as the joint operates in both the full fluid film regime specifically the elastohydrodynamic lubrication (EHL) regime-and the mixed or boundary lubrication regimes, where contact between the bearing surfaces results in wear. In this work, a wear model is developed which considers lubrication for the first time via a transient EHL model of metal-on-metal hip replacements. This is a framework to investigate how the change in film thickness influences the wear, which is important to further investigation of the complex wear procedure, including tribocorrosion, in the lubricated hip implants. The wear model applied here is based on the work of Sharif et al. who adapted the Archard wear law by making the wear rate a function of a relative film thickness nominalized by surface roughness for examining wear of industrial gears. In this work, the gait cycle employed in hip simulator tests is computationally investigated and wear is predicted for two sizes of metal-on-metal total hip replacements. The wear results qualitatively predict the typical wear curve obtained from experimental hip simulator tests, with an initial "running-in period" before a lower wear rate is reached. The shape of the wear scar has been simulated on both the acetabular cup and the femoral head bearing surfaces. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 497-506, 2017. PMID- 26559658 TI - Efficacy and Safety of Citalopram in Treating Post-Stroke Depression: A Meta Analysis. AB - BACKGROUND AND PURPOSE: To evaluate the citalopram in post-stroke depression treatment, we compared its use to other selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and traditional Chinese medicines (TCMs). METHODS: We searched databases up to May 2015. Relative risk (RR) for dichotomous data and standard mean difference (SMD) for continuous variables were analyzed using Stata 13.1. RESULTS: The RR of the efficacy index compared to TCAs was 1.07 (95% CI 1.01-1.14, p = 0.02), and the Hamilton Depression Scale with citalopram was lower than that found with other SSRIs (SMD -0.43, 95% CI -0.85 to -0.01, p < 0.05) and TCAs (SMD -0.31, 95% CI -0.50 to -0.12, p < 0.05) in 6-week. The Treatment Emergent Symptom Scale with citalopram was lower than that with other SSRIs (SMD -0.33, 95% CI -0.56 to -0.10, p = 0.01, 1-week). The p values were all >0.05 on citalopram vs. TCMs. CONCLUSIONS: The efficacy of citalopram maybe not very significant compared to that of other SSRIs or TCAs. But citalopram has fewer side effects especially in the first week. We, however, need further researches to compare citalopram to TCMs in future. PMID- 26559659 TI - Acetoxymethyl Ester of Tetrabromobenzimidazole-Peptoid Conjugate for Inhibition of Protein Kinase CK2 in Living Cells. AB - CK2 is a ubiquitous serine/threonine protein kinase, which has the potential to catalyze the generation of a large proportion of the human phosphoproteome. Due to its role in numerous cellular functions and general anti-apoptotic activity, CK2 is an important target of research with therapeutic potential. This emphasizes the need for cell-permeable highly potent and selective inhibitors and photoluminescence probes of CK2 for investigating the protein phosphorylation networks in living cells. Previously, we had developed bisubstrate inhibitors for CK2 (CK2-targeted ARCs) that showed remarkable affinity (KD < 1 nM) and selectivity, but lacked proteolytic stability and plasma membrane permeability. In this report, the structures of CK2-targeted ARCs were modified for the application in live cells. Based on structure-activity studies, proteolytically stable achiral oligoanionic peptoid conjugates of 4,5,6,7-tetrabromo-1H benzimidazole (TBBz) were constructed. Affinity of the conjugates toward CK2 reached subnanomolar range. Acetoxymethyl (AM) prodrug strategy was applied for loading TBBz-peptoid conjugates into living cells. The uptake of inhibitors was visualized by live cell imaging and the reduction of the phosphorylation levels of two CK2-related phosphosites, Cdc37 pSer13 and NFkappaB pSer529, was demonstrated by Western blot analysis. PMID- 26559660 TI - Solid-state NMR characterization of tri-ethyleneglycol grafted polyisocyanopeptides. AB - In aqueous media, ethylene glycol substituted polyisocyanopeptides (PICPs) change their state (undergo a sol-to-gel transition) as a response to temperature. This makes them promising materials for various biomedical applications, for instance, for controlled drug release and non-damaging wound dressing. To utilize PICP in biomedical applications, understanding of the origin of the gelation process is needed, but this is experimentally difficult because of the notoriously low gelator concentration in combination with the slow polymer dynamics in the sample. This paper describes a detailed characterization of the dried state of PICPs by solid-state NMR measurements. Both the (13) C and the (1) H NMR resonances were assigned using a combination of 1D cross-polarization magic angle spinning, 2D (13) C-(1) H heteronuclear correlation spectra and (1) H-(1) H single quantum-double quantum experiments. In addition, the chemical groups involved in dipolar interaction with each other were used to discuss the dynamics and spatial conformation of the polymer. In contrast to other PICP polymers, two resonances for the backbone carbon are observed, which are present in equal amounts. The possible origin of these resonances is discussed in the last section of this work. The data obtained during the current studies will be further used in elucidating mechanisms of the bundling and gelation. A comprehensive picture will make it possible to tailor polymer properties to meet specific needs in different applications. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26559661 TI - Different effects of olive leaf extract on antioxidant enzyme activities in midbrain and dopaminergic neurons of Substantia Nigra in young and old rats. AB - OBJECTIVES: Study of the effects of olive leaf extract on antioxidant enzyme activities in midbrain and dopaminergic neurons of Substantia Nigra in young and old rats. METHODS: Male wistar rats age 4 and 18 months were randomized into control and experimental groups. A single daily dose of 50 mg/kg of olive leaf extract was administered orally by gavage to each rat for 6 months. The control group received only distilled water. All rats were sacrificed 2 hours after the last gavage and their midbrains were separated for Malondialdehyde (MDA) and antioxidant enzyme activitiy analysis. TUNEL assay and immunohistochemical (IHC) staining were used for evaluation of the number of neurons in the Substantia Nigra. RESULTS: The level of Catalase, Glutathione Peroxidase and Superoxide Dismutase enzyme activity were significantly increased in experimental young and old groups compared to their control groups. However the level of Superoxide Dismutase enzyme activity was significantly increased in experimental old group when compared to control group (P< 0.05), the level of Superoxide Dismutase enzyme activity was not significantly changed in young groups. MDA level was decreased significantly in experimental young and old rats compared to their control groups. Histological analysis demonstrated that the number of neurons in Substantia Nigra of experimental old group was more than the control group (P<0.05). The number of apoptotic cells was significantly decreased in experimental old group compared to the corresponding control group (P<0.05). In IHC and TUNEL assay, no change was observed in the number of neurons between experimental and control young groups. CONCLUSION: Long term treatment with olive leaf extract increases antioxidant enzyme activity and protects the neurons in Substantia Nigra against oxidative stress. PMID- 26559662 TI - Genomic dissection and prediction of heading date in perennial ryegrass. AB - BACKGROUND: Genomic selection (GS) has become a commonly used technology in animal breeding. In crops, it is expected to significantly improve the genetic gains per unit of time. So far, its implementation in plant breeding has been mainly investigated in species farmed as homogeneous varieties. Concerning crops farmed in family pools, only a few theoretical studies are currently available. Here, we test the opportunity to implement GS in breeding of perennial ryegrass, using real data from a forage breeding program. Heading date was chosen as a model trait, due to its high heritability and ease of assessment. Genome Wide Association analysis was performed to uncover the genetic architecture of the trait. Then, Genomic Prediction (GP) models were tested and prediction accuracy was compared to the one obtained in traditional Marker Assisted Selection (MAS) methods. RESULTS: Several markers were significantly associated with heading date, some locating within or proximal to genes with a well-established role in floral regulation. GP models gave very high accuracies, which were significantly better than those obtained through traditional MAS. Accuracies were higher when predictions were made from related families and from larger training populations, whereas predicting from unrelated families caused the variance of the estimated breeding values to be biased downwards. CONCLUSIONS: We have demonstrated that there are good perspectives for GS implementation in perennial ryegrass breeding, and that problems resulting from low linkage disequilibrium (LD) can be reduced by the presence of structure and related families in the breeding population. While comprehensive Genome Wide Association analysis is difficult in species with extremely low LD, we did identify variants proximal to genes with a known role in flowering time (e.g. CONSTANS and Phytochrome C). PMID- 26559663 TI - Comparison of lipid profiles of Malassezia pachydermatis strains isolated from dogs with otitis externa and without clinical symptoms of disease. AB - Malassezia pachydermatis can cause infections of the skin and mucous membranes, especially in animals. It becomes a problem also in medicine. It is considered that metabolic disorders as well as hormonal and immunological status of the host promote diseases caused by M. pachydermatis. Here we consider whether specific features of fungi could also favour infections. We checked whether there are differences in lipid profiles between strains obtained from dogs with otitis externa and strains obtained from healthy dogs. Lipid profiles were determined using thin layer chromatography and gas chromatography-mass spectrometry. All analyses were carried out on 32 strains derived from dogs with otitis externa and 31 strains isolated from dogs without symptoms of disease. The results show that strains isolated from dogs without symptoms of otitis externa are characterised by a higher content of fatty acids. They contain significantly more behenic and lignoceric acids on medium without addition of lipids, and more oleic acid and total monounsaturated fatty acids on medium with lipids supplementation. These strains have also a higher content of esters of ergosterol and triglycerides. Data obtained show differences which may be specific features of M. pachydermatis specific strains related to the ability of infection, which could be not directly related of the host condition. PMID- 26559664 TI - Balancing the risks and benefits of biologic therapy in inflammatory bowel diseases. AB - INTRODUCTION: The incidence of Inflammatory Bowel Diseases (IBD) is rising and overall epidemiology is changing. Goals of IBD therapy are also fast changing to reflect the concept of mucosal healing. IBD management is increasingly revolving around questions of ideal positioning of biologic therapies. AREAS COVERED: This paper covers important concepts regarding two classes of biologic medications approved for treatment of IBD in the United States - anti-TNF-alpha agents and lymphocyte-homing antagonists. Topics covered include drug mechanism of action, pharmacokinetic considerations for the clinician including therapeutic drug monitoring, summary of current evidence of drug efficacy in IBD focusing on randomized, controlled trial data. Additionally, nuanced discussion of medication side-effects and adverse reactions is presented. EXPERT OPINION: Paradigms of treatment goals in IBD are changing with increasing focus on mucosal healing. Concomitantly, our understanding of important factors that impact drug pharmacokinetic/pharmacodynamics relationships with biologic agents has increased which will help eventually develop personalized algorithms to optimize the efficacy of these agents. Though direct head-to-head comparisons between these agents are lacking, biologic agents can be considered the safest and most effective therapies introduced for IBD. PMID- 26559665 TI - Rare transmission of hepatitis B virus by Dutch donors with occult infection. AB - BACKGROUND: To reduce the rate of transfusion-transmitted hepatitis B virus (HBV), HBV DNA testing was introduced for all Dutch blood donations in 2008, in addition to the existing screening for HBV surface antigen (HBsAg). This study describes the lookback results for repeat donors with an "HBV DNA-only" test result (HBV DNA-positive and HBsAg-negative). STUDY DESIGN AND METHODS: From November 2008 until June 2011, a total of 2.3 million blood donations were tested for HBV DNA and 22 donors showed the HBV DNA-only profile. Four donors had early preseroconversion HBV infection, two showed suppressed infection after vaccination, and 16 donors had occult chronic HBV infection (OBI). Potentially infectious donations were traced back as far as 1992. If possible the recipients were tested for current and past HBV infection. RESULTS: A total of 416 implicated donations could be traced in blood bank records, involving 448 issued blood products. For 170 (38%) of the recipients no information was obtained from the hospitals; 196 (44%) recipients had died, and 82 (18%) were tested for HBV. Six recipients tested positive for current (n = 4) or past (n = 2) HBV infection. For two recipients transfusion was ruled out as the source of infection. Three patients showed HBV DNA sequences matching with the HBV in one common OBI donor. Overall, in four of 82 tested recipients (5%) HBV transmission was likely. CONCLUSION: In our lookback study HBV testing was possible in only a minority (18%) of potentially exposed recipients. A low transmission rate (5%) was observed in recipients of blood components from donors with OBI. PMID- 26559666 TI - Prediction of color changes in acetaminophen solution using the time-temperature superposition principle. AB - A prediction method for color changes based on the time-temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l'Eclairage (CIE) LAB color space (a*, b*, L* and DeltaE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time-temperature shift factor of a*, b*, L* and DeltaE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and DeltaE*ab at 40 degrees C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R(2) values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time. PMID- 26559667 TI - Changes in Bone Mineral Density in the Year after Critical Illness. AB - RATIONALE: Critical illness may be associated with increased bone turnover and loss of bone mineral density (BMD). Prospective evidence describing long-term changes in BMD after critical illness is needed to further define this relationship. OBJECTIVES: To measure the change in BMD and bone turnover markers (BTMs) in subjects 1 year after critical illness compared with population-based control subjects. METHODS: We studied adult patients admitted to a tertiary intensive care unit (ICU) who required mechanical ventilation for at least 24 hours. We measured clinical characteristics, BTMs, and BMD during admission and 1 year after ICU discharge. We compared change in BMD to age- and sex-matched control subjects from the Geelong Osteoporosis Study. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients completed BMD testing. BMD decreased significantly in the year after critical illness at both femoral neck and anterior-posterior spine sites. The annual decrease was significantly greater in the ICU cohort compared with matched control subjects (anterior-posterior spine, -1.59%; 95% confidence interval, -2.18 to -1.01; P < 0.001; femoral neck, -1.20%; 95% confidence interval, -1.69 to -0.70; P < 0.001). There was a significant increase in 10-year fracture risk for major fractures (4.85 +/- 5.25 vs. 5.50 +/- 5.52; P < 0.001) and hip fractures (1.57 +/- 2.40 vs. 1.79 +/- 2.69; P = 0.001). The pattern of bone resorption markers was consistent with accelerated bone turnover. CONCLUSIONS: Critically ill individuals experience a significantly greater decrease in BMD in the year after admission compared with population-based control subjects. Their bone turnover biomarker pattern is consistent with an increased rate of bone loss. PMID- 26559668 TI - Developmental DNA methyltransferase inhibitors in the treatment of gynecologic cancers. AB - INTRODUCTION: DNA methylation has become an attractive target for the treatment of cancer. DNA methyltransferase inhibitors have proven useful for the treatment of myelodysplastic syndrome and are being evaluated in gynecological neoplasias. AREAS COVERED: We provide an overview of the current knowledge on DNA methylation and cancer and the role of DNA methylation in cervical, ovarian and endometrial carcinomas. The results of recent clinical trials with demethylating agents for cervical and ovarian cancer treatment are also discussed. EXPERT OPINION: There are few studies of DNA demethylating agents for cervical and ovarian cancer treatment; nevertheless, the results are promising. To accelerate these advances, there are at least two actions that can be simultaneously pursued. One is to greatly increase the number of small clinical exploratory trials with existing demethylating drugs and using methylome analyses to identify predictive factors for response and/or toxicity. The second is finding out epigenetic 'drivers' unique to gynecological cancers and their subtypes, and then proceed to clinical trials in a highly selected population of patients. It is expected that in the future, DNA demethylation could have a role in the treatment of gynecologic cancers. PMID- 26559669 TI - Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson's Disease: A Multimodal Imaging Study. AB - BACKGROUND: Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions. METHODS: Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics. RESULTS: PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe. CONCLUSIONS: Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships. PMID- 26559670 TI - Subcutaneous intravascular papillary endothelial hyperplasia: ultrasound features and pathological correlation. AB - BACKGROUND: To describe grayscale and color Doppler ultrasound features of subcutaneous intravascular papillary endothelial hyperplasia (IPEH). MATERIALS AND METHODS: The ultrasound appearances of ten histologically proven subcutaneous IPEH in ten patients (age range, 15-69 years; mean age, 38.2 years; six females, four males) were reviewed retrospectively by two musculoskeletal radiologists. Color Doppler examination and surgical excision were performed in all cases. The correlations between the ultrasound and pathological features of the lesions were done. RESULTS: All ten cases were pathologically diagnosed as pure forms of IPEH. The mean size of the lesions was 1.3 cm. The margins of the lesions were circumscribed in seven of ten patients. Three had lobular margins. The distinct internal septum-like structures were seen in seven of ten cases (70 %). The vascularity was rich in three (30 %), moderate in four (40 %), and little in three (30 %) of the ten cases. The most common vascular pattern was one or more vessels peripherally or both peripherally and centrally located in the lesion. The detectable origin vessel was noted in four of ten cases (40 %). CONCLUSIONS: Although sonographic features of subcutaneous IPEH are non-specific, they should be included in the differential diagnosis of a small, well-defined, oval or elliptical, heterogeneous, hypoechoic soft tissue mass, showing a vascular pattern of one or more vessels in the lesion and variable vascularity. The presence of the internal septum-like structures and detectable origin vessel may be help to distinguish the lesion from the other soft tissue masses. PMID- 26559671 TI - Fast and Powerful: Biomechanics and Bite Forces of the Mandibles in the American Cockroach Periplaneta americana. AB - Knowing the functionality and capabilities of masticatory apparatuses is essential for the ecological classification of jawed organisms. Nevertheless insects, especially with their outstanding high species number providing an overwhelming morphological diversity, are notoriously underexplored with respect to maximum bite forces and their dependency on the mandible opening angles. Aiming for a general understanding of insect biting, we examined the generalist feeding cockroach Periplaneta americana, characterized by its primitive chewing mouth parts. We measured active isometric bite forces and passive forces caused by joint resistance over the entire mandibular range with a custom-built 2D force transducer. The opening angle of the mandibles was quantified by using a video system. With respect to the effective mechanical advantage of the mandibles and the cross-section areas, we calculated the forces exerted by the mandible closer muscles and the corresponding muscle stress values. Comparisons with the scarce data available revealed close similarities of the cockroaches' mandible closer stress values (58 N/cm2) to that of smaller specialist carnivorous ground beetles, but strikingly higher values than in larger stag beetles. In contrast to available datasets our results imply the activity of faster and slower muscle fibres, with the latter becoming active only when the animals chew on tough material which requires repetitive, hard biting. Under such circumstances the coactivity of fast and slow fibres provides a force boost which is not available during short-term activities, since long latencies prevent a specific effective employment of the slow fibres in this case. PMID- 26559672 TI - CXCL16 signaling mediated macrophage effects on tumor invasion of papillary thyroid carcinoma. AB - Macrophages in tumor microenvironment have pivotal roles in tumor growth, metastasis, and angiogenesis. We investigated the interacting mechanism of macrophage actions in human papillary thyroid cancer (PTC). Co-cultures of macrophage/PTC significantly increased the cancer cell migration potentials, compared with the PTC culture alone. Treatment of conditioned medium (CM) of macrophage/PTC co-cultures enhanced cell invasions in 3D invasion assay. Cytokine array analysis demonstrated that CM of macrophage/PTC co-cultures contained a high level of CXCL16, while it was not found in CM of PTC culture alone. Treatment with CXCL16 enhanced the cell migration potentials in PTC cells, and blocking CXCL16 signaling using anti-CXCL16 antibody or metalloproteinase inhibitor (TAPI2) attenuated macrophage-mediated enhancement of PTC cell migration potentials. In PTC cells, CXCL16 treatment or co-cultures with macrophages increased Akt phosphorylation, and these macrophage-dependent increases of Akt phosphorylation was inhibited by anti-CXCL16 antibody. Moreover, Akt inhibitor attenuated macrophage-mediated increases of PTC cell migration potential. In macrophages, treatment of macrophage/PTC co-cultured CMs up regulated CD163, Il10, and CD206, which were attenuated by anti-CXCL16 antibody treatment. Finally, CXCR6 and CXCL16 expressions were evaluated by immunohistochemical staining with a thyroid tissue microarray including 136 PTC. CXCR6 expressions showed positive correlation with the density of CD163(+) macrophages and associated with lymph node metastasis. In conclusion, CXCL16 signaling partly mediated macrophage actions on PTC tumor cell invasion and also changed the macrophage phenotypes into M2-macrophages in PTC tumor microenvironment. These data suggested that CXCL16 signaling, a bidirectional player in macrophage-associated tumor microenvironment, might be a potential therapeutic target of human PTC. PMID- 26559673 TI - Respiratory Function in Healthy Taiwanese Infants: Tidal Breathing Analysis, Passive Mechanics, and Tidal Forced Expiration. AB - BACKGROUND: Although infant lung function (ILF) testing is widely practiced in developed Western countries it is not typically performed in Eastern countries, and lung measurements are scarce for Asian infants. Therefore, this study aimed to establish normal reference values for Taiwanese infants. MATERIALS AND METHODS: Full-term infants without any chronic diseases and major anomalies were enrolled in the Prediction of Allergies in Taiwanese Children (PATCH) cohort study. Detailed medical data, such as body weight and length, birth history, and histories of previous illness and hospitalization were recorded. Lung function measurements such as analysis of tidal breathing, passive respiratory mechanics, and forced tidal expiratory flow-volume curves were obtained through Jaeger Masterscreen BabyBody Paediatrics System. Multiple linear analyses were performed to determine various parameters of the lung function tests. RESULTS: ILF test parameters were collected from 126 infants, and 189 tests were performed. The results revealed that the ratio of time to peak expiratory flow to total expiratory time, the ratio of volume to peak expiratory flow to total expiratory volume, and the ratio of inspiratory time to total respiratory time remained relatively constant despite differences in age. However, body length is the strongest independent variable influencing tidal volume, respiratory rate, resistance, compliance, and maximal expiratory flow at functional residual capacity. CONCLUSION: According to our review of relevant literature, this is the first study to establish a reference data of ILF tests in the Asian population. This study provided reference values and regression equations for several variables of lung function measurements in healthy infants aged less than 2 years. With these race-specific reference data, ILF can more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity. PMID- 26559674 TI - Secretoglobin 3A2 Exhibits Anti-Fibrotic Activity in Bleomycin-Induced Pulmonary Fibrosis Model Mice. AB - OBJECTIVE: Secretoglobin (SCGB) 3A2 is a novel lung-enriched cytokine, previously shown to exhibit anti-inflammatory, growth factor, and anti-fibrotic activities. The latter activity was demonstrated using exogenously-administered recombinant SCGB3A2 in the bleomycin (BLM)-induced pulmonary fibrosis model. Whether SCGB3A2 exhibits anti-fibrotic activity in vivo is not known. METHODS: Mice null for the Scgb3a2 gene were subjected to the BLM-induced pulmonary fibrosis model, and the severity of pulmonary fibrosis determined using histological and biochemical methods. RESULTS: BLM treatment caused weight loss of both Scgb3a2-null and wild type mice, however, the loss was far more pronounced in BLM-treated Scgb3a2-null than wild-type mice, and the weight of day 21 of BLM-treated Scgb3a2-null mice was about half of that of BLM-treated wild-type mice. Hematoxylin & Eosin, Masson Trichrome, and Sirius Red staining of lung sections, Ashcroft fibrosis scores, hydroxyproline contents, and the levels of mRNAs encoding various collagens demonstrated that BLM-treated Scgb3a2-null mouse lungs had more severe fibrosis than those of wild-type mouse lungs. Total and differential inflammatory cell numbers in bronchoalveolar lavage fluids, and levels of lung mRNAs including those encoding Th2 cytokines such as IL-4 and profibrotic cytokines such as TGFbeta were higher in BLM-treated Scgb3a2-null mouse lungs as compared to those of wild-type mouse lungs. In contrast, mRNAs encoding surfactant proteins A, B, C, and D, and SCGB1A1 did not differ between BLM-treated Scgb3a2-null and wild type mouse lungs. CONCLUSION: The role of SCGB3A2 in fibrosis was revisited using Scgb3a2-null mice and littermate controls in the BLM-induced pulmonary fibrosis model. The pulmonary fibrosis in the Scgb3a2-null mice was more severe than the wild-type controls, thus establishing that SCGB3A2 has anti-fibrotic activity in vivo. Importantly, surfactant proteins and SCGB1A1 appear not to be involved in the susceptibility of Scgb3a2-null mice to BLM-induced pulmonary fibrosis. PMID- 26559675 TI - A Systematic Review of Interventions to Change Staff Care Practices in Order to Improve Resident Outcomes in Nursing Homes. AB - BACKGROUND: We systematically reviewed interventions that attempted to change staff practice to improve long-term care resident outcomes. METHODS: Studies met criteria if they used a control group, included 6 or more nursing home units and quantitatively assessed staff behavior or resident outcomes. Intervention components were coded as including education material, training, audit and feedback, monitoring, champions, team meetings, policy or procedures and organizational restructure. RESULTS: Sixty-three unique studies were broadly grouped according to clinical domain-oral health (3 studies), hygiene and infection control (3 studies), nutrition (2 studies), nursing home acquired pneumonia (2 studies), depression (2 studies) appropriate prescribing (7 studies), reduction of physical restraints (3 studies), management of behavioral and psychological symptoms of dementia (6 studies), falls reduction and prevention (11 studies), quality improvement (9 studies), philosophy of care (10 studies) and other (5 studies). No single intervention component, combination of, or increased number of components was associated with greater likelihood of positive outcomes. Studies with positive outcomes for residents also tended to change staff behavior, however changing staff behavior did not necessarily improve resident outcomes. Studies targeting specific care tasks (e.g. oral care, physical restraints) were more likely to produce positive outcomes than those requiring global practice changes (e.g. care philosophy). Studies using intervention theories were more likely to be successful. Program logic was rarely articulated, so it was often unclear whether there was a coherent connection between the intervention components and measured outcomes. Many studies reported barriers relating to staff (e.g. turnover, high workload, attitudes) or organizational factors (e.g. funding, resources, logistics). CONCLUSION: Changing staff practice in nursing homes is possible but complex. Interventionists should consider barriers and feasibility of program components to impact on each intended outcome. PMID- 26559676 TI - Clinical Predictors for Delayed or Inappropriate Initial Diagnosis of Type A Acute Aortic Dissection in the Emergency Room. AB - BACKGROUND: Initial diagnosis of acute aortic dissection (AAD) in the emergency room (ER) is sometimes difficult or delayed. The aim of this study is to define clinical predictors related to inappropriate or delayed diagnosis of Stanford type A AAD. METHODS: We conducted a retrospective analysis of 127 consecutive patients with type A AAD who presented to the ER within 12 h of symptom onset (age: 69.0 +/- 15.4 years, male/female = 49/78). An inappropriate initial diagnosis (IID) was considered if AAD was not included in the differential diagnosis or if chest computed tomography or echocardiography was not performed as initial imaging tests. Clinical variables were compared between IID and appropriate diagnosis group. The time to final diagnosis (TFD) was also evaluated. Delayed diagnosis (DD) was defined as TFD > third quartile. Clinical factors predicting DD were evaluated in comparison with early diagnosis (defined as TFD within the third quartile). In addition, TFD was compared with respect to each clinical variable using a rank sum test. RESULTS: An IID was determined for 37% of patients. Walk-in (WI) visit to the ER [odds ratio (OR) 2.6, 95% confidence interval (CI) = 1.01-6.72, P = 0.048] and coronary malperfusion (CM, OR = 6.48, 95% CI = 1.14-36.82, P = 0.035) were predictors for IID. Overall, the median TFD was 1.5 h (first/third quartiles = 0.5/4.0 h). DD (>4.5 h) was observed in 27 cases (21.3%). TFD was significantly longer in WI patients (median and first/third quartiles = 1.0 and 0.5/2.85 h for the ambulance group vs. 3.0 and 1.0/8.0 h for the WI group, respectively; P = 0.003). Multivariate analysis revealed that WI visit was the only predictor for DD (OR = 3.72, 95% CI = 1.39 9.9, P = 0.009). TFD was significantly shorter for appropriate diagnoses than for IIDs (1.0 vs. 6.0 h, respectively; P < 0.0001). CONCLUSIONS: WI visit to the ER and CM were predictors for IID, and WI was the only predictor for DD in acute type A AAD in the community hospital. PMID- 26559677 TI - Rho GDIalpha Modulates Rabbit Trophoblast Stem Cell Survival and Migration. AB - Trophoblast stem cells differentiate into different trophoblast cell populations that are indispensable for successful pregnancy through interactions with the maternal uterine decidua. Rho GTPases play an important role in the regulation of trophoblast stem cell (TSC) self-renewal and differentiation; however, the role of Rho GDP-dissociation inhibitors (Rho GDIs) remains unclear. Here we report that overexpression of Rho GDIalpha resulted in rapid apoptosis of TSCs, while its knockdown promoted proliferation. Moreover, Rho GDIalpha knockdown also enhanced TSC invasion. Collectively, these results establish a potential mechanism whereby TSCs can balance growth and apoptosis, and thus ensure normal fetal development. PMID- 26559679 TI - Temporal Release, Paracrine and Endocrine Actions of Ovine Conceptus-Derived Interferon-Tau During Early Pregnancy. AB - The antiviral activity of interferon (IFN) increases in uterine vein serum (UVS) during early pregnancy in sheep. This antiviral activity in UVS collected on Day 15 of pregnancy is blocked by anti-IFN-tau (anti-IFNT) antibodies. Conceptus derived IFNT was hypothesized to induce IFN-stimulated gene (ISG) expression in endometrium and extrauterine tissues during pregnancy. To test this hypothesis, blood was collected from ewes on Days 12-16 of the estrous cycle or pregnancy. Serum progesterone was >1.7 ng/ml in pregnant (P) and nonpregnant (NP) ewes until Day 13, then declined to <0.6 ng/ml by Day 15 in NP ewes. A validated IFNT radioimmunoassay detected IFNT in uterine flushings (UFs) on Days 13-16 and in UVS on Days 15-16 of pregnancy. IFNT detection in UF correlated with paracrine induction of ISGs in the endometrium and occurred prior to the inhibition of estrogen receptor 1 and oxytocin receptor expression in uterine epithelia on Day 14 of pregnancy. Induction of ISG mRNAs in corpus luteum (CL) and liver tissue occurred by Day 14 and in peripheral blood mononuclear cells by Day 15 in P ewes. Expression of mRNAs for IFN signal transducers and ISGs were greater in the CL of P than that of NP ewes on Day 14. It is concluded that: 1) paracrine actions of IFNT coincide with detection of IFNT in UF; 2) endocrine action of IFNT ensues through induction of ISGs in peripheral tissues; and 3) IFNT can be detected in UVS, but not until Days 15-16 of pregnancy, which may be limited by the sensitivity of the IFNT radioimmunoassay. PMID- 26559678 TI - The Role of Retinoic Acid (RA) in Spermatogonial Differentiation. AB - Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia. PMID- 26559680 TI - Impact of Sedation on Cognitive Function in Mechanically Ventilated Patients. AB - The practice of sedation dosing strategy in mechanically ventilated patient has a profound effect on cognitive function. We conducted a comprehensive review of outcome of sedation on mental health function in critically ill patients on mechanical ventilation in the intensive care unit (ICU). We specifically evaluated current sedative dosing strategy and the development of delirium, post traumatic stress disorders (PTSDs) and agitation. Based on this review, heavy dosing sedation strategy with benzodiazepines contributes to cognitive dysfunction. However, outcome for mental health dysfunction is mixed in regard to newer sedatives agents such as dexmedetomidine and propofol. Moreover, studies that examine the impact of sedatives for persistence of PTSD/delirium and its long-term cognitive and functional outcomes for post-ICU patients are frequently underpowered. Most studies suffer from low sample sizes and methodological variations. Therefore, larger randomized controlled trials are needed to properly assess the impact of sedation dosing strategy on cognitive function. PMID- 26559681 TI - The C677T MTHFR genotypes influence the efficacy of B9 and B12 vitamins supplementation to lowering plasma total homocysteine in hemodialysis. AB - BACKGROUND: Hyperhomocysteinaemia, an independent risk factor for cardiovascular diseases, is common in hemodialysis patients (HD) and particularly in those homozygous for polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. B vitamins supplementation has been shown to lower plasma total homocysteine (tHcy), but this has been contreversed in several groups. The aim of our study was to explore the response of tHcy in hemodialysis (HD) patients to individual supplementation with folic acid (B9) and/or vitamin B12, based on carrier status for the (MTHFR) polymorphism. METHODS: 132HD were randomized according to C677TMTHFR genotypes into 2 groups (AandB). The group (A) was treated initially with B9 (10mg/day orally) for 2 months (t1) and then with B12 vitamin (cyanocobalamin ampoule of 1000 MUg) for the following 2 months (t2), then association of B9 and B12 for 2 months (t3). The group (B) was supplemented initially with vitamin B12 (t1), then with folic acid (t2) and then B9 + B12 for 2 months (t3). A wash-out period of 2 months followed the treatment in both groups (t4). We determined tHcy, B9 and B12 concentrations at each time. RESULTS: In group A, we noted that the decrease in tHcy becomes significant for CC when patients were supplemented with vit B12 only (p = 0.009). While, B9 + vit B12 supplementation did not seem to improve a significant effect compared with B12 alone. For genotypes (CT) and (TT) we noticed a significant decrease in tHcy at t1 (p = 0.038; 0.005 respectively) and at (t3; CT p = 0.024; TT p = 0.017). In group B, for genotypes CC, the decrease in tHcy became significant at t3 (vit B12 + B9; p = 0.031). For genotypes (CT) and (TT), at the replacement of vit B12 by B9, tHcy was significantly decreased (p = 0.036; 0.012, respectively). The combination of the 2 vitamins (t3) showed no difference compared to folate alone. In the 2 groups (t4), there was an significant increase of tHcy again for 3 genotypes. CONCLUSION: Supplementation with B vitamins correlated to the MTHFR genotypes has been shown to lower significantly tHcy in HD patients. PMID- 26559682 TI - Characterizing Protease Specificity: How Many Substrates Do We Need? AB - Calculation of cleavage entropies allows to quantify, map and compare protease substrate specificity by an information entropy based approach. The metric intrinsically depends on the number of experimentally determined substrates (data points). Thus a statistical analysis of its numerical stability is crucial to estimate the systematic error made by estimating specificity based on a limited number of substrates. In this contribution, we show the mathematical basis for estimating the uncertainty in cleavage entropies. Sets of cleavage entropies are calculated using experimental cleavage data and modeled extreme cases. By analyzing the underlying mathematics and applying statistical tools, a linear dependence of the metric in respect to 1/n was found. This allows us to extrapolate the values to an infinite number of samples and to estimate the errors. Analyzing the errors, a minimum number of 30 substrates was found to be necessary to characterize substrate specificity, in terms of amino acid variability, for a protease (S4-S4') with an uncertainty of 5 percent. Therefore, we encourage experimental researchers in the protease field to record specificity profiles of novel proteases aiming to identify at least 30 peptide substrates of maximum sequence diversity. We expect a full characterization of protease specificity helpful to rationalize biological functions of proteases and to assist rational drug design. PMID- 26559683 TI - Transmission network of the 2014-2015 Ebola epidemic in Sierra Leone. AB - Understanding the growth and spatial expansion of (re)emerging infectious disease outbreaks, such as Ebola and avian influenza, is critical for the effective planning of control measures; however, such efforts are often compromised by data insufficiencies and observational errors. Here, we develop a spatial-temporal inference methodology using a modified network model in conjunction with the ensemble adjustment Kalman filter, a Bayesian inference method equipped to handle observational errors. The combined method is capable of revealing the spatial temporal progression of infectious disease, while requiring only limited, readily compiled data. We use this method to reconstruct the transmission network of the 2014-2015 Ebola epidemic in Sierra Leone and identify source and sink regions. Our inference suggests that, in Sierra Leone, transmission within the network introduced Ebola to neighbouring districts and initiated self-sustaining local epidemics; two of the more populous and connected districts, Kenema and Port Loko, facilitated two independent transmission pathways. Epidemic intensity differed by district, was highly correlated with population size (r = 0.76, p = 0.0015) and a critical window of opportunity for containing local Ebola epidemics at the source (ca one month) existed. This novel methodology can be used to help identify and contain the spatial expansion of future (re)emerging infectious disease outbreaks. PMID- 26559684 TI - Coupled catastrophes: sudden shifts cascade and hop among interdependent systems. AB - An important challenge in several disciplines is to understand how sudden changes can propagate among coupled systems. Examples include the synchronization of business cycles, population collapse in patchy ecosystems, markets shifting to a new technology platform, collapses in prices and in confidence in financial markets, and protests erupting in multiple countries. A number of mathematical models of these phenomena have multiple equilibria separated by saddle-node bifurcations. We study this behaviour in its normal form as fast-slow ordinary differential equations. In our model, a system consists of multiple subsystems, such as countries in the global economy or patches of an ecosystem. Each subsystem is described by a scalar quantity, such as economic output or population, that undergoes sudden changes via saddle-node bifurcations. The subsystems are coupled via their scalar quantity (e.g. trade couples economic output; diffusion couples populations); that coupling moves the locations of their bifurcations. The model demonstrates two ways in which sudden changes can propagate: they can cascade (one causing the next), or they can hop over subsystems. The latter is absent from classic models of cascades. For an application, we study the Arab Spring protests. After connecting the model to sociological theories that have bistability, we use socioeconomic data to estimate relative proximities to tipping points and Facebook data to estimate couplings among countries. We find that although protests tend to spread locally, they also seem to 'hop' over countries, like in the stylized model; this result highlights a new class of temporal motifs in longitudinal network datasets. PMID- 26559685 TI - Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma. AB - Plaques vulnerable to rupture are characterized by a thin and stiff fibrous cap overlaying a soft lipid-rich necrotic core. The ability to measure local plaque stiffness directly to quantify plaque stress and predict rupture potential would be very attractive, but no current technology does so. This study seeks to validate the use of Brillouin microscopy to measure the Brillouin frequency shift, which is related to stiffness, within vulnerable plaques. The left carotid artery of an ApoE(-/-)mouse was instrumented with a cuff that induced vulnerable plaque development in nine weeks. Adjacent histological sections from the instrumented and control arteries were stained for either lipids or collagen content, or imaged with confocal Brillouin microscopy. Mean Brillouin frequency shift was 15.79 +/- 0.09 GHz in the plaque compared with 16.24 +/- 0.15 (p < 0.002) and 17.16 +/- 0.56 GHz (p < 0.002) in the media of the diseased and control vessel sections, respectively. In addition, frequency shift exhibited a strong inverse correlation with lipid area of -0.67 +/- 0.06 (p < 0.01) and strong direct correlation with collagen area of 0.71 +/- 0.15 (p < 0.05). This is the first study, to the best of our knowledge, to apply Brillouin spectroscopy to quantify atherosclerotic plaque stiffness, which motivates combining this technology with intravascular imaging to improve detection of vulnerable plaques in patients. PMID- 26559688 TI - Delivery of a Cell Patch of Cocultured Endothelial Cells and Smooth Muscle Cells Using Thermoresponsive Hydrogels for Enhanced Angiogenesis. AB - Cell-based therapy has been studied as an attractive strategy for therapeutic angiogenesis. However, obtaining a stable vascular structure remains a challenge due to the poor interaction of transplanted cells with native tissue and the difficulty in selecting the optimal cell source. In this study, we developed a cell patch of cocultured human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) using thermosensitive hydrogels for regeneration of mature vasculatures. In vitro characterization of HUVECs in the cocultured group revealed the formation of a mesh-like morphology over 5 days of culture. Vascular endothelial growth factor expression was also upregulated in the cocultured group compared with HUVECs only. The cell patch seeded with HUVECs, SMCs, or both cell type was prepared on the synthetic thermosensitive and cell interactive hydrogels, and readily detached from the hydrogel within 10 min by expansion of the hydrogel when the temperature was decreased to 4 degrees C. We then investigated the therapeutic effect of the cell patch using a hind limb ischemic model of an athymic mouse. Overall, the group that received a cell patch of cocultured HUVECs and SMCs had a significantly retarded rate of necrosis with a significant increase in the number of arterioles and capillaries for 4 weeks compared with the groups transplanted with only HUVECs or SMCs. Dual staining of smooth muscle alpha actin and human nuclear antigen showed that the implanted cell patch was partially involved in vessel formation. In summary, the simple transplantation of a cocultured cell patch using a hydrogel system could enhance therapeutic angiogenesis through the regeneration of matured vascular structures. PMID- 26559686 TI - Heme Oxygenase-1 Protects Neurons from Ischemic Damage by Upregulating Expression of Cu,Zn-Superoxide Dismutase, Catalase, and Brain-Derived Neurotrophic Factor in the Rabbit Spinal Cord. AB - In the present study, we investigated the protective effects of heme oxygenase (HO-1) against ischemic damage in motor neurons of the rabbit spinal cord. A PEP 1-HO-1 fusion protein was made to and confirmed the effective the penetration of HO-1 into spinal cord neurons at 8 h after treatment. Transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15 min. Vehicle (glycerol) or 0.375 mg/kg PEP-1-HO-1 was administered intraperitoneally to rabbits immediately after ischemia/reperfusion. Animals were sacrificed 15 min after reperfusion to measure lactate levels; 24 h after reperfusion to measure caspase 3 and myeloperoxidase levels, lipid peroxidation, and the activity of Cu,Zn-superoxide dismutase (SOD1) and catalase (CAT); or 72 h after reperfusion to assess neuronal survival and measure the levels of brain-derived neurotrophic factor (BDNF) in spinal cord homogenates. Administration of PEP-1-HO-1 did not significantly alter arterial blood gases (PaCO2 and PaO2), pH, or blood glucose levels before ischemia, 10 min after occlusion, or 10 min after reperfusion. Mean arterial pressure was selectively reduced 10 min after occlusion. Administration of PEP-1-HO-1 improved the rabbit Tarlov scores, and increased neuronal survival, as assessed by NeuN immunohistochemical staining 72 h after ischemia/reperfusion. In addition, administration of PEP-1-HO-1 significantly ameliorated lactate accumulation 15 min after reperfusion, and the increases in caspase 3, myeloperoxidase, and lipid peroxidation 24 h after reperfusion. PEP-1-HO-1 administration significantly mitigated the decrease in SOD1 and CAT 24 h after reperfusion, and reversed the decrease in BDNF levels in spinal cord homogenates 72 h after ischemia/reperfusion. These results suggest that PEP-1-HO-1 can protect against neuronal damage after transient spinal cord ischemia by limiting early lactic acidosis and increasing SOD1, CAT, and BDNF levels. PMID- 26559687 TI - Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate Induced Toxicity in PC12 Cells. AB - Etidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a 'germinal bisphosphonate' unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P-C-P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca(2+) channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca(2+), are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 MUM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10-100 MUM TrisPP showed remarkable cell protection (78-86 %). Moreover, pre treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca(2+) overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents. PMID- 26559689 TI - Vorapaxar in the secondary prevention of atherothrombosis. AB - Dual antiplatelet therapy with aspirin, a platelet cyclooxygenase-1 inhibitor and P2Y12 receptor blockers, remains the major drug strategy to prevent ischemic event occurrence in patients with acute coronary syndromes and in patients undergoing coronary stenting, but there some limitations that can be overcome by targeting novel targets. Unlike direct thrombin inhibitors that bind directly to thrombin, targeting the platelet thrombin receptor, protease activated receptor (PAR)-1, may offer a better choice for the attenuation of atherosclerosis progression, thrombus-mediated ischemic events and restenosis without interfering with primary hemostasis. Vorapaxar - a synthetic analogue of himbacine, is a high affinity and highly selective PAR-1 antagonist that can effectively inhibit thrombin-induced platelet aggregation. In the TRACER trial, the addition of vorapaxar to standard therapy in patients with non-stent thrombosis-elevation- acute coronary syndromes did not significantly reduce the primary composite end point occurrence of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for ischemia, or urgent revascularization, but significantly increased the GUSTO moderate and severe bleeding (p < 0.001) and intracranial hemorrhage (ICH). In the TRA 2 degrees P-TIMI 50 trial, in patients with a history of MI and peripheral arterial disease (PAD) (67% of the total population), the end point of CV death, MI, or stroke was significantly (20%) reduced with vorapaxar whereas GUSTO moderate or severe bleeding was increased (1.5-fold), but not ICH or fatal bleeding and the net clinical outcome favoring the vorapaxar therapy. Based on these favorable results, the FDA approved vorapaxar for the reduction of thrombotic cardiovascular events in patients with prior MI or with PAD for long term therapy. A careful patient selection is needed to balance efficacy versus safety. At this time, patients with high risk for recurrent ischemic event occurrence such as patients with diabetes mellitus and previous MI can be safely treated with vorapaxar for long-term therapy. PMID- 26559690 TI - Antibacterial activity of achievable epithelial lining fluid exposures of Amikacin Inhale with or without meropenem. AB - OBJECTIVES: While Amikacin Inhale (BAY41-6551), an integrated drug-device combination under development, achieves an estimated amikacin epithelial lining fluid (ELF) concentration of ~ 5000 mg/L, its target site pharmacodynamics are unknown. We evaluated the pharmacodynamics of ELF exposure of inhaled amikacin +/ meropenem. METHODS: ELF exposures of inhaled amikacin (400 mg every 12 h), intravenous meropenem (2 g every 8 h) and a combination of both were studied in an in vitro pharmacodynamic model. Seven Klebsiella pneumoniae and 10 Pseudomonas aeruginosa with amikacin/meropenem MICs of 1 to 32,768/<= 0.125 to >128 mg/L were included. Efficacy was assessed over 24-72 h. RESULTS: The mean +/- SD 0 h bacterial density was 6.5 +/- 0.1 log10 cfu/mL. Controls grew to 8.0 +/- 0.5 log10 cfu/mL by the end of the experiments. Simulation of inhaled amikacin monotherapy rapidly achieved and sustained bactericidal activity near the limit of detection over 24 h for all 13 isolates with amikacin MIC <= 256 mg/L except only ~ 2 log10 cfu/mL reduction was observed in K. pneumoniae 375 (amikacin/meropenem MIC 64/32 mg/L) and P. aeruginosa 1544 (amikacin/meropenem MIC 64/128 mg/L). No activity was seen against the three isolates with amikacin MIC >= 2048 mg/L. Among the six isolates tested with meropenem monotherapy, five (meropenem MIC >= 16 mg/L) grew similarly to the controls while one (meropenem MIC 2 mg/L) achieved ~ 2.5 log10 cfu/mL decrease. Among seven isolates tested in combination, four (amikacin/meropenem MIC <= 64/32 mg/L), including K. pneumoniae 375, maintained limit of detection until 72 h, whereas P. aeruginosa 1544 sustained a 1 log reduction. Combination therapy had no activity against the two isolates with amikacin MIC >= 2048 mg/L. CONCLUSIONS: Inhaled amikacin monotherapy showed bactericidal activity against most isolates tested with amikacin MICs <= 256 mg/L. Adjunct inhaled amikacin plus meropenem sustained this activity for 72 h for the tested isolates with amikacin/meropenem MIC <= 64/32 mg/L. PMID- 26559691 TI - Insights into Trx1, TRP14, and Prx1 homologs of Paralichthys olivaceus: molecular profiles and transcriptional responses to immune stimulations. AB - Thioredoxin (Trx) proteins are involved in several cellular processes, such as anti-oxidative stress and cellular redox homeostasis. In this study, we isolated the full-length cDNAs of PoTrx1 and PoTRP14 from Japanese flounder (Paralichthys olivaceus). PoTrx1 is 723 bp in length, with a 366-bp open reading frame (ORF) that encodes for 121 amino acids. PoTRP14 is 909 bp in length, with a 372-bp ORF that encodes for 123 amino acids. PoTrx1 and PoTRP14 are highly conserved in Cys Gly-Pro-Cys and Cys-Pro-Asp-Cys forms, respectively. Tissue distribution analysis revealed that the transcripts of PoTrx1 and PoTRP14 were ubiquitously expressed in all tested tissues and particularly abundant in immunity-related organs, such as the liver, intestine, gill, and spleen. Development expression profiles indicated that PoTrx1 transcript was expressed from the neurula stage to the 1 day post-hatching stage; the maximum transcript levels were recorded at the somatic stage. The mRNA level of PoTRP14 was constantly expressed at all examined developmental stages, reaching the peak at the before-hatching stage. Prx1 is a peroxiredoxin family member that serves similar functions to PoTrx1 and PoTRP14. A primary hepatocyte culture system was established to examine the immunoregulatory properties of PoTrx1, PoTRP14, and Prx1 in response to lipopolysaccharide, CuSO4, and H2O2 stimulation. Results revealed that the transcript levels of PoTrx1, PoTRP14, and Prx1 were significantly up-regulated in a time-dependent manner after the immunostimulant challenge. These data suggest that PoTrx1, PoTRP14, and Prx1 play critical roles in anti-oxidation and immunoregulation. PMID- 26559692 TI - The antioxidant system of seminal fluid during in vitro storage of sterlet Acipenser ruthenus sperm. AB - The role of the seminal fluid antioxidant system in protection against damage to spermatozoa during in vitro sperm storage is unclear. This study investigated the effect of in vitro storage of sterlet Acipenser ruthenus spermatozoa together with seminal fluid for 36 h at 4 degrees C on spermatozoon motility rate and curvilinear velocity, thiobarbituric acid reactive substance level, and components of enzyme and non-enzyme antioxidant system (superoxide dismutase and catalase activity and uric acid concentration) in seminal fluid. Spermatozoon motility parameters after sperm storage were significantly decreased, while the level of thiobarbituric acid reactive substances, activity of superoxide dismutase and catalase, and uric acid concentration did not change. Our findings suggest that the antioxidant system of sterlet seminal fluid is effective in preventing oxidative stress during short-term sperm storage and prompt future investigations of changes in spermatozoon homeostasis and in spermatozoon plasma membrane structure which are other possible reasons of spermatozoon motility deterioration upon sperm storage. PMID- 26559693 TI - Cancer after intense and prolonged antiplatelet therapies--fact or fiction? PMID- 26559694 TI - Corrigendum. AB - Bakas, P., Boutas, I., Creatsa, M., Vlahos, N., Gregoriou, O., Creatsas, G., and Hassiakos, D. (2015). Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation? http://dx.doi.org/10.3109/09513590.2015.1025381. When the above article was first published online on August 2015, Dimitrios Hassiakos' name is missing. This has now been corrected in online version.The author apologises for this error. PMID- 26559695 TI - The Anti-Inflammatory Effects of Lion's Mane Culinary-Medicinal Mushroom, Hericium erinaceus (Higher Basidiomycetes) in a Coculture System of 3T3-L1 Adipocytes and RAW264 Macrophages. AB - Chronic low-grade inflammation in the adipose tissue accompanying obesity is thought to be an underlying driver of metabolic diseases. In this study, we aimed to investigate the efficacy of Hericium erinaceus on adipose tissue inflammation. The anti-inflammatory effects of the ethyl acetate soluble fraction of H. erinaceus (EAHE) were examined using cocultures of 3T3-L1 adipocytes and RAW264 macrophages. EAHE significantly suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production in cultured RAW264 macrophages stimulated by lipopolysaccharide (LPS). EAHE also caused notable inhibition of c-Jun N-terminal kinase (JNK) activation, which is thought to be involved in the suppression of proinflammatory cytokines by EAHE. In a coculture system with 3T3-L1 and RAW264 cells stimulated with LPS, EAHE reduced TNF-alpha and IL-6 concentrations in the conditioned medium and lowered the gene expression levels of these cytokines in 3T3-L1 adipocytes. Furthermore, EAHE suppressed the LPS-induced reduction of adiponectin mRNA levels in 3T3-L1 adipocytes cocultured with RAW264 macrophages. However, in 3T3-L1 adipocytes cultured alone, the concentration of LPS used in this study did not affect the gene expression levels of these adipokines. We attributed the anti-inflammatory effects of EAHE on 3T3-L1 adipocytes cocultured with RAW264 macrophages to the suppression of Toll-like receptor 4 (TLR4) signaling and subsequent proinflammatory cytokine secretion in RAW264 cells. Our findings indicate the possibility that H. erinaceus exerts anti-inflammatory effects on macrophages through the inhibition of TLR4-JNK signaling and prevents or ameliorates adipose tissue inflammation associated with obesity. PMID- 26559696 TI - Protective Effect of Eburicoic Acid of the Chicken of the Woods Mushroom, Laetiporus sulphureus (Higher Basidiomycetes), Against Gastric Ulcers in Mice. AB - In this study, we investigated the anti-inflammatory and tumor-inhibiting effects of eburicoic acid, the main bioactive component in the Laetiporus sulphureus, on gastric ulcers. A total of 48 Kunming mice were randomly divided into six groups: control, model, OL (omeprazole, 20 mg/kg/day, orally), EA-L (eburicoic acid, 10 mg/kg/day, orally), EA-M (eburicoic acid, 20 mg/kg/day, orally), and EA-H (eburicoic acid, 40 mg/kg/day, orally). Gastric ulcers were induced in mice by administering 80% ethanol containing 15 mg/mL aspirin (10.0 mL/kg, i.g.) 4 hours after drug administration on day 5. The ulcer index and H+/K+-ATPase activity were evaluated in vivo. Computer-aided molecular docking simulated the interaction between eburicoic acid and H+/K+-ATPase. The results showed that the oral administration of eburicoic acid protected the gastric mucosa from gastric lesions morphologically and especially attenuated H+/K+-ATPase activity. The results of this study indicate that the gastric protective effect of eburicoic acid might inhibit gastric acid. PMID- 26559697 TI - Antioxidant Properties of Oak Bracket Mushroom, Pseudoinonotus dryadeus (Higher Basidiomycetes): A Mycochemical Study. AB - A complex mixture of free fatty acids (1), cerevisterol (2), a sphingosine (3), and a complex mixture of diacylglycerophospholipids (4) were isolated from the fruiting body of the basidiomycete mushroom Pseudoinonotus dryadeus and subjected to spectroscopic analyses. The antioxidant activities of the whole extract of the fungus, of the isolated fractions, and of compounds 1-4 were evaluated in two in vitro model systems: 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and superoxide anion. In each systems, the extract of fungus and compound 2 showed the same free radical scavenging activity (with SC50 data of 18.27 ug/mL and 5.75 ug/mL, respectively) compared with the positive control quercetin (DPPH assay). Compounds 1-4 were isolated from P. dryadeus for the first time. PMID- 26559698 TI - Enhanced Bioactive Exopolysaccharide Production by Mossy Maze Polypore, Cerrena unicolor (Higher Basidiomycetes) in Submerged Culture Conditions. AB - In this study, the culture requirements of the Cerrena unicolor OBCC 5005 strain were determined to optimize bioactive exopolysaccharide production in submerged culture. The effects of initial medium pH, carbon and nitrogen sources, inoculum age and amount, and mineral source on exopolysaccharide and mycelial biomass production by the C. unicolor OBCC 5005 strain were studied using a one-factor-at a-time method. The highest exopolysaccharide production was obtained when culture parameters were used as initial medium pH: 5.5, 5% sucrose, 5% mycological peptone, and 5% of 4-day inoculants in the presence of 5 mM Fe2+. Optimized culture conditions at a flask scale were applied to a 3-L stirred tank reactor. As a result, 7.92 g/L and 7.34 g/L maximum exopolysaccharide production in optimized conditions at flask and stirred-tank reactor scales were achieved, respectively. The present study is the first to prove that C. unicolor can yield high bioactive exopolysaccharide production at flask and stirred-tank reactor scales. PMID- 26559699 TI - Chemical Composition and Medicinal Value of Fruiting Bodies and Submerged Cultured Mycelia of Caterpillar Medicinal Fungus Cordyceps militaris CBS-132098 (Ascomycetes). AB - In this paper, we report the results of a proximate analysis (i.e., moisture, ash, protein, fat, carbohydrates, and energy); a bioactive compounds analysis (i.e., cordycepin and ergothioneine); fatty and amino acid analysis; and analyses of vitamin content, macro- and microelement composition of fruiting body (FB), and mycelial biomass (MB) of medicinal caterpillar fungus Cordyceps militaris strain CBS-132098. These results demonstrate that the FB and MB of C. militaris are good sources of proteins: 59.8% protein content in the FB and 39.5% in the MB. The MB was distinguished by its carbohydrate content (39.6%), which was higher than that of the FB (29.1% carbohydrate). In the FB of C. militaris, the total amino acid content was 57.39 mg/g and in the MB it was 24.98 mg/g. The quantification of the identified fatty acids indicated that palmitic acid, oleic acid, linoleic acid, and linolenic acid were the major fatty acids. The micro- and macroelement compositions were studied. The highest results were calcium (797 mg/kg FB; 11 mg/kg MB); potassium (15,938 mg/kg FB 12,183 mg/kg MB); magnesium (4,227 mg/kg FB; 3,414 mg/kg MB); sodium (171 mg/kg FB; 1,567 mg/kg MB); phosphorus (7,196 mg/kg FB; 14,293 mg/kg MB); and sulfur (5,088 mg/kg FB; 2,558 mg/kg MB). The vitamin composition was studied, and the most abundant vitamins were vitamin A, vitamin B3, and vitamin E. The bioactive components were cordycepin, cordycepic acid (D-mannitol), and ergothioneine. There were differences in cordycepin and ergothioneine contents between the FB and the MB. The cordycepin concentration was 0.11% in the FB and 0.182% in the MB, the cordycepic acid was 4.7 mg/100g in the FB and 5.2 mg/100 g in the MB, and the ergothioneine content was 782.37 mg/kg in the FB and 130.65 mg/kg in the MB. The nutritional values of the FB and the MB of C. militaris detected indicate its potential use in well-balanced diets and sources of bioactive compounds. PMID- 26559700 TI - Evaluation of Mycelial Nutrients, Bioactive Compounds, and Antioxidants of Five Himalayan Entomopathogenic Ascomyceteous Fungi from India. AB - In this study, using standard methods, mycelial nutrients, bioactive compounds, and antioxidants were analyzed for the first time for five fungal species: Isaria sinclairii (Berk.) Lloyd, I. tenuipes Peck, I. japonica Yasuda, I. farinosa (Holmsk) Fr. and Cordyceps tuberculata (Lebert) Maire. All of these species were low in fat content and rich in protein, fiber, ash, and carbohydrates. Mineral elements (Fe, Mg, Cu, Mn, and Ca) were detected in appreciable amounts. All three types of fatty acids (saturated, monounsaturated, and polyunsaturated) as well as bioactive compounds (ascorbic acid, beta-carotene, lycopene, phenolic compounds, and polysaccharides) were detected for each species. The investigated species showed high ferric-reducing antioxidant power as well as 2,2-diphenyl-1-picryl hydrazyl radical scavenging activity. Although differences were observed in the values of each species, each species showed richness in one or more components. PMID- 26559701 TI - In Vitro and In Vivo Antioxidant Effects of Polysaccharides from Nameko Medicinal Mushroom, Pholiota nameko SW-01 (Higher Basidiomycetes). AB - Extra- (EPS) and intracellular polysaccharides (IPS) from Pholiota nameko SW-01 were extracted, and in vitro and in vivo antioxidant effects were processed. Briefly, the in vitro antioxidant results indicated that the inhibition effects of IPS at a dose of 500 mg/L on superoxide anions, hydroxyl radicals, and 1,1 diphenyl-2-picrylhydrazyl (DPPH) radicals were 63.24 +/- 1.12%, 53.11 +/- 2.92%, and 59.33 +/- 9.37%, which were 7.70%, 14.84%, and 11.40% higher than those of EPS, and 9.79%, 20.32%, and 4.59% higher than those of butylated hydroxytoluene (BHT), respectively. The reducing power of IPS reached 0.593 +/- 0.21 (absorbance at 700 nm), which was 11.30% higher than that of EPS and 15.51% higher than that of BHT. In vivo antioxidant results proved that both IPS and EPS significantly upregulated the enzyme activities of superoxide dismutase (SOD), GSH peroxide (GSH-Px), catalase (CAT), and alanine transaminase (ALT). In addition, glycosidic bond types of EPS and IPS were primarily characterized. The findings indicate the potential antioxidant effects of polysaccharide extract from Ph. Nameko. Thus, this species has potential applicability as an antioxidant agent and should be studied further. PMID- 26559702 TI - Optimization of Liquid Fermentation Medium for Production of Inonotus sanghuang (Higher Basidiomycetes) Mycelia and Evaluation of their Mycochemical Contents and Antioxidant Activities. AB - Inonotus sanghuang, an authentic "Sanghuang" mushroom used in traditional Chinese medicine, is known to possess important pharmacological activities. In this study, we aimed to optimize the liquid fermentation medium for I. sanghuang mycelial production and to determine the effects of two-stage cultivation (shake and static) on the yield of total flavonoids, total phenolics, and polysaccharides, as well as the antioxidant activities of I. sanghuang mycelial extracts (ISME). Under an optimized medium composition (38.96 g/L of corn flour, 4.15 g/L of yeast extract, 20.55 g/L of bran and pH 6.39), the predicted and experimental optimal mycelial biomasses were 17.60 g/L and 18.33+/-0.86 g/L, respectively. The results of two-stage cultivation showed that contents of total flavonoids and total phenolics in mycelia increased by 37.92% and 77.27%, respectively. However, irregular polysaccharide contents were noted throughout the experimental period. Antioxidant assays showed that ISME possessed good free radical scavenging activity, which is mainly contributed by polyphenolic-type metabolites. PMID- 26559703 TI - Review on Natural Enemies and Diseases in the Artificial Cultivation of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes). AB - Ophiocordyceps sinensis (syn. Cordyceps sinensis), well known as DongChongXiaCao (DCXC), is one of the most valuable traditional Chinese medicinal species. In this article, we provide a systematic review of natural enemies and diseases encountered in artificial cultivation of DCXC. Unfortunately, DCXC has been endangered over the past decades due to overharvesting and a worsening ecological environment. Therefore, the artificial cultivation of DCXC has been extensively investigated in recent years. Complete indoor artificial cultivation and semi field cultivation are the two most common strategies used to cultivate DCXC. However, cultured DCXCs are often attacked by various natural enemies and diseases, which have resulted in substantial loss of the valuable medicinal resource. In this study, we have summarized the species of natural enemies and types of diseases confronted by DCXC. Twenty reported natural enemy species are categorized into four classes, one of which is reported for the first time in this study. Moreover, six microbial pathogens are also discussed. The recapitulation of the natural enemies and diseases in DCXC artificial cultivation not only promote the development of integrated pest management of DCXC cultivation but also provide important information to help preserve and develop this valuable resource. PMID- 26559704 TI - Improved outcome of bacterial meningitis associated with use of corticosteroid treatment. AB - Background The aim of this study was to evaluate the clinical outcome of patients with bacterial meningitis following the introduction of dexamethasone treatment in Denmark. Methods Adult patients with bacterial meningitis, admitted from 2003 2010 to two different university hospitals, were included retrospectively. Data at clinical presentation, Glasgow outcome scale (GOS), cerebrospinal fluid and blood biochemistry were collected. Relative risk (RR) with 95% confidence interval (CI) was computed by Cox proportional hazard regression analysis. Results One hundred and forty-seven patients were included in the study. The population had a median age of 62 years and 31% had an immunosuppressive co morbidity. Eighty-nine patients had an unfavourable outcome (GOS score = 1-4). Adjuvant treatment with corticosteroids (RR = 0.48; 95% CI = 0.30-0.76) was associated with a favourable outcome (GOS score = 5), while altered mental status (RR = 2.36; 95% CI = 1.17-4.78) and age (RR = 1.03; 95% CI = 1.01-1.04) per year increment was associated with an unfavourable outcome. Adjuvant corticosteroid treatment did not affect short- or long-term survival. Short-term mortality was influenced by age (RR = 1.06; 95% CI = 1.04-1.09). Long-term mortality was influenced by age (RR = 1.06; 95% CI = 1.03-1.08) and female sex (RR = 1.81; 95% CI = 1.05-3.14). Conclusion This study indicated that adjuvant corticosteroid treatment in acute bacterial meningitis improves the outcome and can safely be administered in an elderly population with high levels of immunosuppressive co morbidity. PMID- 26559705 TI - The antimicrobial properties of ginseng and ginseng extracts. AB - Ginseng is commonly used in traditional Chinese medicine as a tonic and an adaptogen to reduce fatigue and boost the immune system. In recent years, ginseng extracts are shown to have both bacteriostatic and bactericidal actions and seem to exert their effects by several mechanisms, including disruption of biofilms, inhibition of quorum-sensing and virulence factors, and altering motility. Also, ginseng extracts are shown to have antifungal properties as demonstrated by their ability to inhibit the growth of several mold and yeast species. Extracts from ginseng root have a strong antiviral activity against the RNA viruses in cell cultures and animal models. In addition to the antimicrobial activities, ginseng extracts are shown to possess immunomodulatory properties involved in the amelioration of infections. The present paper describes the antimicrobial effects of ginseng and its extracts. PMID- 26559706 TI - Anterior cruciate ligament tears for the primary care sports physician: what to know on the field and in the office. AB - Anterior cruciate ligament (ACL) injuries are relatively common and can lead to knee dysfunction. The classic presentation is a non-contact twisting injury with an audible pop and the rapid onset of swelling. Prompt evaluation and diagnosis of ACL injuries are important. Acute treatment consists of cessation of the sporting activity, ice, compression, and elevation with evaluation by a physician familiar with ACL injuries and their management. The diagnosis is made with the use of patient history and physical examination as well as imaging studies. Radiographs may show evidence of a bony injury. MRI confirms the diagnosis and evaluates the knee for concomitant injuries to the cartilage, menisci and other knee ligaments. For active patients, operative treatment is often recommended while less-active patients may not require surgery. The goal of this review is to discuss the diagnosis of an ACL injury and provide clear management strategies for the primary-care sports medicine physician. PMID- 26559707 TI - Snacking, Satiety, and Weight: A Randomized, Controlled Trial. AB - PURPOSE: To compare the effects of nut-based snack bars (NBSB) vs. prepackaged 200-kcal portions of typical conventional snack foods, when consumed over a 12 week period by a group of overweight adults. DESIGN: Randomized, single-blind parallel design with two treatment groups. SETTING: CLINICAL TRIAL: SUBJECTS: Thirty-four overweight participants were enrolled. INTERVENTION: Commercially available NBSB or conventional snack foods as part of an ad libitum diet for 12 weeks. MEASURES: PRIMARY OUTCOME MEASURES: body mass index, body weight, body composition, waist circumference. SECONDARY OUTCOME MEASURES: blood pressure, lipid profile, nutrients intake, hunger/satiety, quality of life. ANALYSIS: Generalized linear models with time as repeated measure were used to analyze these data. RESULTS: Daily consumption of NBSB for 12 weeks, as compared to daily consumption of conventional snacks, significantly reduced percentage body fat ( 1.7% +/- 10.8% vs. 6.2% +/- 9.3%; p = .04) and visceral fat (-1.3 +/- 5.9 vs. 2.7 +/- 4.0; p = .03). There were no between-group differences (p > .05) for blood pressure, lipid panel, satiety, or quality of life measures. CONCLUSION: Our data suggest that daily consumption of NBSB for 12 weeks reduced body fat and had no adverse effects on weight, blood pressure, lipid profile, satiety, or quality of life in this small sample of overweight adults. PMID- 26559708 TI - Impact of California Children's Power Play! Campaign on Fruit and Vegetable Intake and Physical Activity among Fourth- and Fifth-Grade Students. AB - PURPOSE: Examine the impact of the Children's Power Play! Campaign on fruit and vegetable (FV) intake and physical activity (PA). DESIGN: Study design was a cluster randomized, controlled trial. SETTING: Forty-four low-resource public schools in San Diego County, California, were included in the study. SUBJECTS: Study subjects comprised a total of 3463 fourth/fifth-graders (1571 intervention, 1892 control), with an 86.9% completion rate. INTERVENTION: Throughout 10 weeks, activities were conducted during/after school, including weekly FV/PA lessons and PA breaks; biweekly classroom promotions/taste tests; posters displayed in/around schools; and weekly nutrition materials for parents. MEASURES: Self-reported FV intake (cups/d) and PA (min/d) were collected at baseline and follow-up using a diary-assisted, 24-hour dietary recall and Self-Administered Physical Activity Checklist. ANALYSIS: Multivariate regression models adjusted for demographics and cluster design effects were used, with change as the dependent variable. RESULTS: Intervention children, compared with controls, showed gains in daily FV intake (.26 cups, p < .001) and PA time at recess/lunch (5.1 minutes, p = .003), but not total daily PA minutes. CONCLUSION: Power Play! can help schools and community organizations improve low-income children's FV intake and PA during recess/lunch. PMID- 26559709 TI - Advancing School and Community Engagement Now for Disease Prevention (ASCEND). AB - PURPOSE: To compare two intensity levels (standard vs. enhanced) of a nutrition and physical activity intervention vs. a control (usual programs) on nutrition knowledge, body mass index, fitness, academic performance, behavior, and medication use among elementary school students. DESIGN: Quasi-experimental with three arms. SETTING: Elementary schools, students' homes, and a supermarket. SUBJECTS: A total of 1487 third-grade students. INTERVENTION: The standard intervention (SI) provided daily physical activity in classrooms and a program on making healthful foods, using food labels. The enhanced intervention (EI) provided these plus additional components for students and their families. MEASURES: Body mass index (zBMI), food label literacy, physical fitness, academic performance, behavior, and medication use for asthma or attention-deficit hyperactivity disorder (ADHD). ANALYSIS: Multivariable generalized linear model and logistic regression to assess change in outcome measures. RESULTS: Both the SI and EI groups gained less weight than the control (p < .001), but zBMI did not differ between groups (p = 1.00). There were no apparent effects on physical fitness or academic performance. Both intervention groups improved significantly but similarly in food label literacy (p = .36). Asthma medication use was reduced significantly in the SI group, and nonsignificantly (p = .10) in the EI group. Use of ADHD medication remained unchanged (p = .34). CONCLUSION: The standard intervention may improve food label literacy and reduce asthma medication use in elementary school children, but an enhanced version provides no further benefit. PMID- 26559710 TI - The Effect of Changes in Physical Activity on Sedentary Behavior: Results From a Randomized Lifestyle Intervention Trial. AB - PURPOSE: To investigate whether changes in physical activity (PA) have an impact on sedentary behavior (SB) during a lifestyle intervention. DESIGN: Study design was a randomized trial. SETTING/SUBJECTS: Participants (n = 204) were individuals with low PA and high sedentary leisure screen time from the Chicago area. INTERVENTION: Participants were randomized to either increase PA (iPA) or decrease sedentary leisure (dSED). The intervention consisted of decision support, coaching, and financial incentives. For iPA participants, the goal was at least 60 min/d of self-reported moderate-tovigorous-intensity PA (MVPA). For dSED participants the goal was less than 90 min/d of sedentary leisure screen time. MEASURES: Daily accelerometer-based measures of SB and bout-corrected MVPA were obtained. ANALYSIS: Linear mixed-effects models were fit to estimate the effect of the intervention on MVPA and total SB and to estimate the effect of daily changes in MVPA on daily SB. RESULTS: The iPA participants increased their bout-corrected MVPA by 14 min/d (p < .001) and decreased their total SB by 18 min/d (p < .001). The dSED participants did not significantly change their PA or their total SB. On days when participants exercised, each 10-minute bout of MVPA was associated with a 6-minute decrease in SB on the same day (p < .001). CONCLUSION: In an intervention study designed to increase MVPA, participants who increase their time spent exercising will obtain much of this time by reducing their SB. PMID- 26559711 TI - New Pathways From Short Sleep to Obesity? Associations Between Short Sleep and "Secondary" Eating and Drinking Behavior. AB - PURPOSE: The association between short sleep and obesity risk is well established. However, we explore a new pathway between short sleep and obesity: whether short sleep is linked to more time spent in secondary eating or drinking, that is, eating or drinking (beverages other than water, such as sugar-sweetened beverages) while primarily engaged in another activity, such as television watching. DESIGN: This pooled cross-sectional study uses data from the American Time Use Survey (ATUS) from 2006 to 2008. SETTING: The study takes place in the United States. SUBJECTS: Subjects are 28,150 adults (55.8% female) aged 21 to 65 who were surveyed in the ATUS. MEASURES: Outcomes are time spent on (1) secondary eating and drinking and (2) primary eating and drinking. Our main predictor variable is sleep duration. ANALYSIS: Controlling for demographic and socioeconomic characteristics of the respondents, we estimate multivariate regression-analysis models for the full sample, as well as by weekday/weekend status, race, and gender subgroups. RESULTS: In multivariate models, compared to respondents reporting normal sleep, short sleep was associated with additional 8.7 (SE = 2.1) minutes per day of secondary eating (p < .01) and additional 28.6 (SE = 4.2) and 31.28 (SE = 5.0) minutes per day of secondary drinking on weekdays and weekends, respectively (p < .01). CONCLUSIONS: We find that short sleep is associated with more time spent in secondary eating and, in particular, secondary drinking. This potentially suggests a pathway from short sleep to increased caloric intake in the form of beverages and distracted eating and thus potential increased obesity risk, although more research is needed. PMID- 26559712 TI - Active8! Technology-Based Intervention to Promote Physical Activity in Hospital Employees. AB - PURPOSE: Increase physical activity in health care employees using health messaging, and compare e-mail with mobile phone short-message service (SMS) as delivery channels. DESIGN: Randomized controlled trial Setting. U.K. hospital workplace. SUBJECTS: Two hundred ninety-six employees (19-67 years, 53% of study Web site visitors). INTERVENTION: Twelve-week messaging intervention designed to increase physical activity and delivered via SMS (n =147) or e-mail (n =149); content tailored using theory of planned behavior (TPB) and limited to 160 characters. MEASURES: Baseline and 6, 12, and 16 weeks. Online measures included TPB constructs, physical activity behavior on the Global Physical Activity Questionnaire, and health-related quality of life on the Short-Form 12. ANALYSIS: General linear models for repeated measures. RESULTS: Increase in duration (mean h/d) of moderate work-related activity and moderate recreational activity from baseline to 16 weeks. Short-lived increase in frequency (d/wk) of vigorous recreational activity from baseline to 6 weeks. Increase in duration and frequency of active travel from baseline to 16 weeks. E-mails generated greater changes than SMS in active travel and moderate activity (work and recreational). CONCLUSION: Minimal physical activity promotion delivered by SMS or e-mail can increase frequency and duration of active travel and duration of moderate intensity physical activity at work and for leisure, which is maintained up to 1 month after messaging ends. Both channels were useful platforms for health communication; e-mails were particularly beneficial with hospital employees. PMID- 26559713 TI - Which Type of Antismoking Advertisement Is Perceived as More Effective? An Experimental Study With a Sample of Australian Socially Disadvantaged Welfare Recipients. AB - PURPOSE: Evaluate the perceived effectiveness of key antismoking messages among highly disadvantaged smokers and assess the impact of nicotine dependence and cessation cognitions on message processing. DESIGN: The experimental crossover trial, undertaken between March and December 2012, randomly exposed participants to two of three antismoking advertisements delivered via touchscreen computer. SETTING: Welfare recipients were recruited from a community service organization in New South Wales, Australia. SUBJECTS: Subjects were 354 smokers (79% response rate). Participants resided in government rental housing (52%), earned less than AUD$400/wk (72%), and received their primary income from government welfare (95%). INTERVENTION: Three 30-second antismoking television advertisements representing common campaign themes: why to quit (graphic imagery), why to quit (personal testimonial), or how to quit. MEASURES: An 11-item scale assessed perceived effectiveness and message acceptance. An eight-item cessation cognitions index assessed motivations and readiness to quit, and the heaviness of smoking index was used to classify nicotine dependence. ANALYSIS: Descriptive statistics, generalized linear mixed models, and multiple linear regression analyses are reported. RESULTS: Why-to-quit advertisements were perceived as significantly more effective than the how-to-quit advertisement (all p < .0001). Smokers with positive cessation cognitions were more likely to accept antismoking messages (p = .0003) and perceive them as effective (p < .0001). Nicotine dependence level did not influence message acceptance (p = .7322) or effectiveness (p = .8872). CONCLUSION: Highly emotive advertisements providing good reasons to quit may be the most effective in promoting the antismoking message among groups with high smoking rates. PMID- 26559714 TI - Support for Food and Beverage Worksite Wellness Strategies and Sugar-Sweetened Beverage Intake Among Employed U.S. Adults. AB - PURPOSE: Sugar-sweetened beverage (SSB) consumption is high among U.S. adults and is associated with obesity. Given that more than 100 million Americans consume food or beverages at work daily, the worksite may be a venue for interventions to reduce SSB consumption. However, the level of support for these interventions is unknown. We examined associations between workday SSB intake and employees' support for worksite wellness strategies (WWSs). DESIGN: We conducted a cross sectional study using data from Web-based annual surveys that gather information on health-related attitudes and behaviors. SETTING: Study setting was the United States. SUBJECTS: A total of 1924 employed adults (>=18 years) selected using probability-based sampling. MEASURES: The self-reported independent variable was workday SSB intake (0, <1 or >=1 times per day), and dependent variables were employees' support (yes/no) for the following WWSs: (1) accessible free water, (2) affordable healthy food/drink, (3) available healthy options, and (4) less available SSB. ANALYSIS: Multivariable logistic regression was used to control for sociodemographic variables, employee size, and availability of cafeteria/vending machine. RESULTS: About half of employees supported accessible free water (54%), affordable healthy food/drink (49%), and available healthy options (46%), but only 28% supported less available SSB. Compared with non-SSB consumers, daily SSB consumers were significantly less supportive of accessible free water (adjusted odds ratio, .67; p < .05) or less available SSB (odds ratio, .49; p < .05). CONCLUSION: Almost half of employees supported increasing healthy options within worksites, although daily workday SSB consumers were less supportive of certain strategies. Lack of support could be a potential barrier to the successful implementation of certain worksite interventions. PMID- 26559715 TI - "Get drunk. Smoke weed. Have fun.": A Content Analysis of Tweets About Marijuana and Alcohol. AB - PURPOSE: To explore the sentiment and themes of Twitter chatter that mentions both alcohol and marijuana. DESIGN: Cross-sectional analysis of tweets mentioning both alcohol and marijuana during 1 month was performed. SETTING: The study setting was Twitter. PARTICIPANTS: Tweets sent from February 4 to March 5, 2014, were studied. METHOD: A random sample (n = 5000) of tweets that mentioned alcohol and marijuana were qualitatively coded as normalizing both substances, preferring one substance over the other, or discouraging both substances. Other common themes were identified. RESULTS: More than half (54%) of the tweets normalized marijuana and alcohol (without preferring one substance over the other), and 24% preferred marijuana over alcohol. Only 2% expressed a preference for alcohol over marijuana, 7% discouraged the use of both substances, and the sentiment was unknown for 13% of the tweets. Common themes among tweets that normalized both substances included using the substances with friends (17%) and mentioning substance use in the context of sex or romance (14%). Common themes among tweets that preferred marijuana over alcohol were the beliefs that marijuana is safer than alcohol (46%) and preferences for effects of marijuana over alcohol (40%). CONCLUSION: Tweets normalizing polysubstance use or encouraging marijuana use over alcohol use are common. Both online and offline prevention efforts are needed to increase awareness of the risks associated with polysubstance use and marijuana use. PMID- 26559716 TI - Social Smoking and Mental Health Among Chinese Male College Students. AB - PURPOSE: China has a high prevalence of smoking, but the characteristics of social smoking in Chinese college students have not been investigated. We examined the pattern of social smoking and explored the association between social smoking and personal cessation efforts and mental health factors among Chinese male college students. DESIGN: Study design was a cross-sectional survey. SETTING: P. R. China was the setting of the study. SUBJECTS: Participants were a random sample of 1327 male college students. MEASURES: All participants completed a self-administered questionnaire that examined their smoking behaviors and a group of specific mental health factors (loneliness, self-harm, suicide, depression, and anxiety). ANALYSIS: Analysis was conducted using descriptive statistics, chi2 analysis, and multivariate logistic regression. RESULTS: Of a total of 207 current smokers, 102 (49.3%) were identified as social smokers. Compared with nonsmokers, social smokers had increased risks for depression (odds ratio, 1.74; 95% confidence interval, 1.15-2.65). Among daily smokers, social smokers were less likely to have an intention to quit smoking than nonsocial smokers (odds ratio, .08; 95% confidence interval, .01-.57). CONCLUSION: This study reveals unique psychologic characteristics related to social smoking. College students are a particular group of interest because unhealthy behaviors initiated during adolescence may continue through adulthood. Our findings provide evidence for future tobacco control intervention among this population. PMID- 26559717 TI - Exploring Perceptions of Barriers, Facilitators, and Motivators to Physical Activity Among Female Bariatric Patients: Implications for Physical Activity Programming. AB - PURPOSE: To explore barriers, facilitators, and motivators to adopting and maintaining regular physical activity among women with obesity who have undergone bariatric surgery. APPROACH: Individual interviews with women 3 to 24 months post bariatric surgery. SETTING: Participants were recruited from a bariatric clinic in Montreal, Canada. PARTICIPANTS: Twelve women were recruited (mean age = 47 +/- 9 years) using poster advertisements and word of mouth. Participants were on average 15 months postsurgery. METHOD: Each woman was interviewed once using a semistructured interview protocol. Recruitment was conducted until data saturation (i.e., no new information emerged). The interviews were transcribed, coded, and analyzed using inductive thematic analysis. RESULTS: Three interrelated themes emerged: the physical body, appraisal of the physical and social self, and the exercise environment. Barriers included weight-restricted mobility, side effects of surgery, body dissatisfaction, compromised psychological health, competing responsibilities, a lack of exercise self efficacy and social support, reduced access to accommodating facilities, lack of exercise knowledge, and northern climate. Participants reported postsurgical weight loss, weight and health maintenance, enjoyment, body image, and supportive active relationships, as well as access to accommodating facilities and exercise knowledge, as facilitators and motivators. CONCLUSION: Suggested physical activity programming strategies for health care professionals working with this unique population are discussed. Physical activity and health promotion initiatives can also benefit from a cultural paradigm shift away from weight based representations of health. PMID- 26559719 TI - A Qualitative Examination of Smoke-Free Policies and Electronic Cigarettes Among Sheltered Homeless Adults. AB - PURPOSE: To examine attitudes toward smoke-free policies and perceptions of e cigarette use among homeless adults. APPROACH: A cross-sectional qualitative study was conducted. SETTING: Study setting comprised seven transitional homeless shelters with indoor smoke-free policies in San Diego County; facilities differed in outdoor restrictions on smoking. PARTICIPANTS: Sixty-six current or former smokers were the study participants. METHOD: Participants completed a questionnaire on smoking behaviors, perceived antitobacco norms, and attitudes toward smoke-free policies, and attended a focus group interview that explored these topics. We used a directed content analysis approach to analyze the focus group transcripts. RESULTS: Clients in facilities with outdoor restrictions on smoking had stronger perceived antitobacco norms than those in facilities without such restrictions. We identified the following major themes: attitudes toward smoke-free policies, the use of e-cigarettes, the addictive potential of cigarettes, vulnerability to tobacco industry marketing, and interest in smoking cessation. The consensus was that smoke-free policies were important because they limited secondhand smoke exposure to nonsmokers and children. All were curious about e-cigarettes, particularly if they could be smoked in areas where smoking was prohibited and/or used as a cessation aid. CONCLUSION: In this study of homeless adults, there was strong support for indoor and outdoor smoke-free policies. However, misperceptions that e-cigarettes could be used indoors could threaten antitobacco norms, highlighting opportunities to educate about the potential risks of e-cigarette use among homeless individuals. PMID- 26559718 TI - Perinatal Illicit Drug and Marijuana Use. AB - PURPOSE: To assess use, screening, and disclosure of perinatal marijuana and other illicit drugs during first obstetric visits. DESIGN: Observational study that qualitatively assesses provider screening and patient disclosure of substance use. SETTING: Study sites were five urban outpatient prenatal clinics and practices located in Pittsburgh, Pennsylvania. PARTICIPANTS: Pregnant patients and obstetric providers were recruited as participants. METHODS: We audio recorded patient-provider conversations during first obstetric visits and obtained patient urine samples for drug analyses. Audio recordings were reviewed for provider screening and patient disclosure of illicit drug use. Urine analyses were compared with audio recordings to determine disclosure. RESULTS: Four hundred and twenty-two pregnant patients provided complete audio recordings and urine samples for analyses. Providers asked about illicit drug use in 81% of the visits. One hundred twenty-three patients (29%) disclosed any current or past illicit drug use; 48 patients (11%) disclosed current use of marijuana while pregnant. One hundred and forty-five samples (34%) tested positive for one or more substances; marijuana was most commonly detected (N = 114, 27%). Of patients who tested positive for any substance, 66 (46%) did not disclose any use; only 36% of patients who tested positive for marijuana disclosed current use. CONCLUSION: Although marijuana is illegal in Pennsylvania, a high proportion of pregnant patients used marijuana, with many not disclosing use to their obstetric care providers. PMID- 26559721 TI - Rural Print Media and a Tailored Advocacy Intervention for Smoke-Free Policy. AB - PURPOSE: To examine frequency, prominence, and content of local print media after a 4-year policy advocacy intervention. DESIGN: This was a controlled community based trial. SETTING: The study took place in 39 rural counties (22 intervention, 17 comparison). SUBJECTS: Subjects consisted of 2525 newspaper articles monitored over 18 quarters (July 2007 to December 2011). INTERVENTION: One key element of the tailored policy advocacy intervention delivered by community advisors was building demand for smoke-free policy via media advocacy strategies. MEASURES: Media clips were coded to assess number of articles; percent of tobacco-related articles on the front page or bold heading section; percent of pro-health articles; and percent of articles with secondhand smoke (SHS)-relevant topics or themes. ANALYSIS: Coded data were entered into Atlas.ti software. Article frequencies and attributes were compared between groups and over time using negative binomial regression for longitudinal data, with county-level demographics as covariates. RESULTS: In the last 3 years, there were approximately twice as many articles in intervention than in comparison counties. Media clips from newspapers in intervention counties were between 1.4 and 2 times more likely to have front page placement and percent of relevant topic or theme than were those in comparison counties. There was no difference in rate of pro health articles by group. CONCLUSION: The policy advocacy intervention to promote smoke-free policy increased media attention to SHS and may have increased public awareness of issues related to smoke-free policy. PMID- 26559720 TI - Telephone-Based Coaching. AB - PURPOSE: Many Americans continue to smoke, increasing their risk of disease and premature death. Both telephone-based counseling and in-person tobacco cessation classes may improve access for smokers seeking convenient support to quit. Little research has assessed whether such programs are effective in real-world clinical populations. DESIGN: Retrospective cohort study comparing wellness coaching participants with two groups of controls. SETTING: Kaiser Permanente Northern California, a large integrated health care delivery system. SUBJECTS: Two hundred forty-one patients who participated in telephonic tobacco cessation coaching from January 1, 2011, to March 31, 2012, and two control groups: propensity-score matched controls, and controls who participated in a tobacco cessation class during the same period. Wellness coaching participants received an average of two motivational interviewing-based coaching sessions that engaged the patient, evoked their reason to consider quitting, and helped them establish a quit plan. MEASURES: Self-reported quitting of tobacco and fills of tobacco cessation medications within 12 months of follow-up. ANALYSIS: Logistic regressions adjusting for age, gender, race/ethnicity, and primary language. RESULTS: After adjusting for confounders, tobacco quit rates were higher among coaching participants vs. matched controls (31% vs. 23%, p < .001) and comparable to those of class attendees (31% vs. 29%, p = .28). Coaching participants and class attendees filled tobacco-cessation prescriptions at a higher rate (47% for both) than matched controls (6%, p < .001). CONCLUSION: Telephonic wellness coaching was as effective as in-person classes and was associated with higher rates of quitting compared to no treatment. The telephonic modality may increase convenience and scalability for health care systems looking to reduce tobacco use and improve health. PMID- 26559722 TI - Perceptions of Food Intake, Physical Activity, and Obesity Among African-American Children in the Lower Mississippi Delta. AB - PURPOSE: To explore the nutrition and physical activity perceptions of children for planning a healthy weight curriculum to address childhood obesity in African American children living in the Lower Mississippi Delta (LMD). DESIGN: Six children's focus group sessions. SETTING: Two Louisiana parishes in the LMD. SUBJECTS: Seventy 8- to 13-year-old African-American children, 46 (66%) females and 24 (44%) males, participated in the focus group sessions. MEASURES: Interview questions were based on personal and environmental determinants and content and strategies for a healthy lifestyle program for children. ANALYSIS: Focus group discussions were audio recorded and transcribed, observer recorded, and analyzed to identify recurring trends and patterns among focus groups. Content analysis consisted of coding focus group transcripts for recurrent themes and review of data by an independent reviewer to confirm the themes. RESULTS: Emerging themes were categorized as healthy lifestyle opinions within the social cognitive theory constructs of personal and environmental determinants and curriculum content. CONCLUSION: LMD youth recognized a healthy eating pattern and that overweight and obesity result from poor eating habits and physical inactivity. Children's food intake pattern did not reflect this understanding, suggesting a need for culturally tailoring an intervention to impact the poor food intake and physical inactivity in two low-income African-American Delta communities. PMID- 26559723 TI - Hippocampal dysregulation of FMRP/mGluR5 signaling in engrailed-2 knockout mice: a model of autism spectrum disorders. AB - Many evidences indicate that mice lacking the homeobox transcription factor engrailed-2 (En2(-/-) mice) represent a reliable model to investigate neurodevelopmental basis and gene expression changes relevant to autism spectrum disorders. Dysfunctions in fragile X mental retardation protein (FMRP), metabotropic glutamate receptor 5 (mGluR5), and GABAergic signaling pathways have been proposed as a possible pathogenic mechanism of autism spectrum disorders. Here, we exploited En2(-/-) mice to investigate hippocampal expression of FMRP, mGluR5, and GABA(A) receptor beta3 subunit (GABRB3). Quantitative reverse transcription PCR showed that all these mRNAs were significantly downregulated in En2(-/-) mice compared with wild-type littermates. Western blot and immunohistochemistry confirmed the downregulation of FMRP and GABRB3 proteins, while showing a significant increase of mGluR5 protein in the En2(-/-) hippocampus. Our results suggest that the dysregulation of FMRP-mGluR5 signaling pathway, accompanied with a downregulation of GABRB3 expression, may contribute to the 'autistic-like' features observed in En2 mice, providing possible molecular targets for future pharmacological studies. PMID- 26559724 TI - Secure attachment status is associated with white matter integrity in healthy young adults. AB - The present study investigates associations between security of attachment in the mother-child relationship and patterns of brain connectivity in young adults. We hypothesized that secure attachment would relate to more efficient connectivity in white matter association fibers due to increased myelination. Attachment security was measured in 53 young adults using the Kerns Security Scale; anatomical information was acquired using diffusion tensor imaging. Higher fractional anisotropy, an index of directionality of diffusion, related to security of attachment in four left-hemisphere white matter association fibers (uncinate fasciculus, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus). As expected, this result was mainly ascribable to increased myelination, which has been independently associated with attachment security. Security of attachment may have an identifiable biological basis. Our research demonstrates the feasibility of coupling neuroimaging tools with clinical investigation. PMID- 26559725 TI - Cerebral gray matter volume variation in female-to-male transsexuals: a voxel based morphometric study. AB - Several studies seem to support the hypothesis that brain anatomy is associated with transsexualism. However, these studies were still limited because few neuroanatomical findings have been obtained from female-to-male (FtM) transsexuals. This study compared the cerebral regional volumes of gray matter (GM) between FtM transsexuals and female controls using a voxel-based morphometry. Twelve FtM transsexuals who had undergone sex-reassignment surgery and 15 female controls participated in this study. Both groups were age matched and right-handed, with no history of neurological illness. Fifteen female controls were recruited to determine whether GM volumes in FtM transsexuals more closely resembled individuals who shared their biological sex. MRI data were processed using SPM 8 with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL). FtM transsexuals showed significantly larger volumes of the thalamus, hypothalamus, midbrain, gyrus rectus, head of caudate nucleus, precentral gyrus, and subcallosal area compared with the female controls. However, the female controls showed a significantly larger volume in the superior temporal gyrus including Heschl's gyrus and Rolandic operculum. These findings confirm that the volume difference in brain substructures in FtM transsexuals is likely to be associated with transsexualism and that transsexualism is probably associated with distinct cerebral structures, determining gender identity. PMID- 26559727 TI - A study of brain white matter plasticity in early blinds using tract-based spatial statistics and tract statistical analysis. AB - Early blind individuals are known to exhibit structural brain reorganization. Particularly, early-onset blindness may trigger profound brain alterations that affect not only the visual system but also the remaining sensory systems. Diffusion tensor imaging (DTI) allows in-vivo visualization of brain white matter connectivity, and has been extensively used to study brain white matter structure. Among statistical approaches based on DTI, tract-based spatial statistics (TBSS) is widely used because of its ability to automatically perform whole brain white matter studies. Tract specific analysis (TSA) is a more recent method that localizes changes in specific white matter bundles. In the present study, we compare TBSS and TSA results of DTI scans from 12 early blind individuals and 13 age-matched sighted controls, with two aims: (a) to investigate white matter alterations associated with early visual deprivation; (b) to examine the relative sensitivity of TSA when compared with TBSS, for both deficit and hypertrophy of white matter microstructures. Both methods give consistent results for broad white matter regions of deficits. However, TBSS does not detect hypertrophy of white matter, whereas TSA shows a higher sensitivity in detecting subtle differences in white matter colocalized to the posterior parietal lobe. PMID- 26559726 TI - Duration of drug action of dopamine D2 agonists in mice with 6-hydroxydopamine induced lesions. AB - Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6 OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans. PMID- 26559728 TI - Dura-evoked neck muscle activity involves purinergic and N-methyl-D-aspartate receptor mechanisms. AB - We have previously demonstrated that noxious stimulation of craniofacial tissues including the frontal dura reflexly evokes significant increases in neck muscle electromyographic (EMG) activity. The primary aim of this study was to determine whether purinergic receptor mechanisms may be involved in these EMG effects, and whether N-methyl-D-aspartate (NMDA) receptor processes modulate the purinergic mechanisms. Application of the P2X1, P2X3 and P2X2/3 receptor agonist alpha,beta methylene ATP (but not vehicle) to the dural surface evoked a significant (P<0.05) increase in ipsilateral neck EMG activity that could be suppressed by dural or intrathecal application of the selective P2X1, P2X3 and P2X2/3 receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) but not by vehicle; the intrathecal application of 2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist, also significantly reduced the neck EMG activity evoked by dural application of alpha,beta-methylene ATP. These data suggest that purinergic receptor mechanisms contribute to the increased neck activity that can be reflexly evoked by noxious stimulation of the frontal dura, and that NMDA as well as purinergic receptor mechanisms in the medulla may modulate these purinergic related effects. PMID- 26559729 TI - Frontoparietal EEG alpha-phase synchrony reflects differential attentional demands during word recall and oculomotor dual-tasks. AB - To study the relationship between the varying degrees of cognitive load and long range synchronization among neural networks, we utilized a dual-task paradigm combining concurrent word recall working memory tasks and oculomotor tasks that differentially activate the common frontoparietal (FP) network. We hypothesized that each dual-task combination would generate differential neuronal activation patterns among long-range connection during word retention period. Given that the FP alpha-phase synchronization is involved in attentional top-down processes, one would expect that the long-range synchronization pattern is affected by the degrees of dual-task demand. We measured a single-trial phase locking value in the alpha frequency (8-12 Hz) with electroencephalography in healthy participants. Single-trial phase locking value characterized the synchronization between two brain signals. Our results revealed that different amounts of FP alpha-phase synchronization were produced by different dual-task combinations, particularly during the early phase of the word retention period. These differences were dependent on the individual's working memory capacity and memory load. Our study shows that during dual-task, each oculomotor task, which is subserved by distinct neural network, generates different modulation patterns on long-range neuronal activation and FP alpha-phase synchronization seems to reflect these differential cognitive loads. PMID- 26559730 TI - A mixed methods contribution to the study of health public policies: complementarities and difficulties. AB - The use of mixed methods (combining quantitative and qualitative data) is developing in a variety of forms, especially in the health field. Our own research has adopted this perspective from the outset. We have sought all along to innovate in various ways and especially to develop an equal partnership, in the sense of not allowing any single approach to dominate. After briefly describing mixed methods, in this article we explain and illustrate how we have exploited both qualitative and quantitative methods to answer our research questions, ending with a reflective analysis of our experiment. PMID- 26559732 TI - The Default Mode Network Connectivity Predicts Cognitive Recovery in Severe Acquired Brain Injured Patients: A Longitudinal Study. AB - To study the functional connectivity in patients with severe acquired brain injury is very challenging for their high level of disability because of a prolonged period of coma, extended lesions, and several cognitive and behavioral disorders. In this article, we investigated in these patients the default mode network and somatomotor connectivity changes at rest longitudinally, in the subacute and late phase after brain injury. The aim of the study is to characterize such connectivity patterns and relate the observed changes to clinical and neuropsychological outcomes of these patients after a period of intensive neurorehabilitation. Our findings show within the default mode network a disruption of connectivity of medial pre-frontal regions and a significant change of amplitude of internal connections. Notably, strongest changes in functional connectivity significantly correlated to consistent clinical and cognitive recovery. This evidence seems to indicate that the reorganization of the Default Mode Network may represent a valid biomarker for the cognitive recovery in patients with severe acquired brain injury. PMID- 26559731 TI - Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYDTM vaccine? AB - Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYDTM, a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYDTM. PMID- 26559733 TI - Marchetti Vicenzi elastic retrograde nail in the treatment of humeral shaft fractures: review of the current literature. AB - Shoulder impairment following anterograde intramedullary nailing for humeral shaft fractures represents a challenging problem for the orthopedic surgeon. Traditional retrograde nailing lowers the rates of shoulder impairment although exposing the surgeons to severe technical issues related to the proximal interlocking. The Marchetti Vicenzi nail (MVN) permits a retrograde insertion along with a self-locking mechanism that lowers the risk of iatrogenic damage during proximal interlocking. Aim of this literature review was to evaluate all the case series dealing with MVN and the obtained results in terms of union rates, complications, and functional outcomes in order to evaluate evidence that would substantiate the adoption of MVN in the treatment of humeral shaft fractures. A search was performed using the keywords "humeral shaft fracture nail," "humeral retrograde nail," "humeral elastic nail," "Marchetti Vicenzi nail," "Marchetti nail," "Vicenzi nail." After accurate revision 13 articles found to be relevant with a total of 532 humeral fractures (traumatic and pathologic) and non-unions treated with MVN. The cumulative healing rate reported is 93.7 % with 6.3 % of non-unions. Despite the fact that obtained results compare favorably to the published data on the outcome of anterograde nailing, the evaluated studies presented a huge number of methodological flaws, thus making it difficult to recommend the adoption of MVN in preference of other better-validated forms of treatment. PMID- 26559734 TI - Neonatal gram-negative bacillary late-onset sepsis: A case-control-control study on a prospectively collected database of 5,233 admissions. AB - BACKGROUND: Gram-negative bacillary (GNB) bloodstream infections account for 20% 30% of neonatal late-onset sepsis (LOS). We aimed to identify the incidence, clinical characteristics, and risk factors for adverse outcomes in neonates with GNB LOS. METHODS: All patients with GNB LOS admitted to the neonatal intensive care units (NICUs) of a university-affiliated teaching hospital in Taiwan from January 1, 2004-December 31, 2011, were enrolled. A case-control-control study was performed to evaluate risk factors for acquisition of neonatal GNB LOS. RESULTS: Of the 5,010 neonates, 290 (5.8%) had a total of 346 episodes of GNB LOS (36.7% of total LOS), with an incidence rate of 13.6 per 10,000 neonate hospital days. The overall mortality rate was 17.6% (51/290), and the sepsis attributable mortality rate was 9.8% (34/346 episodes). After multivariate logistic regression analysis, neonates with prolonged use of total parenteral nutrition (adjusted odds ratio [OR] = 1.53; 95% confidence interval [CI], 1.02-2.29; P = .041) were independently associated with acquisition of GNB LOS. The independent predictors of in-hospital mortality were Pseudomonas aeruginosa etiology (OR = 11.45; 95% CI, 2.83-46.24) and underlying secondary pulmonary hypertension (OR = 18.02; 95% CI, 3.28-98.89), renal disease (OR = 17.16; 95% CI, 2.96-99.38), and neuromuscular comorbidities (OR = 2.72; 95% CI, 1.06-7.00). CONCLUSION: Given the higher illness severity and sepsis-attributable mortality rate of neonatal GNB LOS in the NICU, strategies to reduce the incidence need to be addressed urgently. PMID- 26559735 TI - Personal protective equipment processes and rationale for the Nebraska Biocontainment Unit during the 2014 activations for Ebola virus disease. AB - In response to the Ebola virus disease outbreak of 2014, specific procedures for personal protective equipment use were developed in the Nebraska Biocontainment Unit for the isolation care of patients with the illness. This brief report describes the 2 different levels used for patient care and presents the rationales for the specialized processes. PMID- 26559736 TI - Microbial contamination of anesthetic syringes in relation to different handling habits. AB - This single-center study prospectively assessed the microbial contamination of anesthetic syringes handled perioperatively under different conditions. We documented high rates of bacterial contamination, with strong but statistically nonsignificant differences between handling groups. Our results identify skin contact as the main source of contamination, and thus we emphasize the impact of proper hand hygiene. PMID- 26559737 TI - It is time to revise our approach to registering antimicrobial agents for health care settings. PMID- 26559738 TI - Emergent health risks and audience information engagement on social media. AB - Social media can effectively reach large audiences and serve as an indicator for the public's sentiment and engagement in situations of disease outbreaks. This study used Centers for Disease Control and Prevention (CDC) Facebook posts between March 18 and October 31, 2014, surrounding the 2014 Ebola outbreak, to look at the audience engagement with online health information. The CDC submitted fewer posts about Ebola than about non-Ebola topics, but audience engagement with Ebola posts was significantly higher, and men were more interested in Ebola posts and submitted more comments per user. PMID- 26559739 TI - Tyrosine-kinases inhibitors in recurrent platinum-resistant ovarian cancer patients. AB - For many decades, ovarian cancer (OC) has been one of the most common gynecological cancer. Despite advances in OC diagnosis and treatment, the risk of recurrence is ever present and approximately 85% of patients will experience relapse. Recurrent OC after first-line therapy is almost always incurable. Multiple novel therapies, including tyrosine-kinases inhibitors (TKI), have shown promising results, but their role needs to be clarified. In this review we describe the rationale and the clinical evidence regarding the use of TKI for the treatment of recurrent platinum-resistant OC patients. PMID- 26559740 TI - Cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients receiving concurrent chemoradiation. AB - BACKGROUND: Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. METHODS: From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. RESULTS: From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. CONCLUSIONS: Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. CLINICAL TRIAL INFORMATION: NCT01439724. PMID- 26559741 TI - Adolescent Suicide Rates Between 1990 and 2009: Analysis of Age Group 15-19 Years Worldwide. AB - PURPOSE: The aim of the current analysis is to analyze suicide rates in adolescents aged 15-19 years in decades between 1990 and 2009 worldwide. METHODS: Suicide data were obtained from the World Health Organization Mortality Database and population data from the World Bank Data set. In total, 81 countries or territories, having data at least for 5 years in 1990-1999 and in 2000-2009, were included in the analysis. Additional analysis for regional trends with 57 countries was performed. RESULTS: Over the decades considered, analysis showed a declining trend in the overall suicide rate for males from 10.30 to 9.51 per 100,000 (p = .076), and for females from 4.39 to 4.18 (p = .472). The average suicide rate showed a significant decline for both genders in Europe, dropping from 13.13 to 10.93 (p = .001) in males and from 3.88 to 3.34 in females (p = .038). There was a significant increase in South American countries for males, from 7.36 to 11.47 (p = .016), and a close to significant rise for females, from 5.59 to 7.98 (p = .053). Although other world regions did not show significant trends, there were several significant changes at country level. CONCLUSIONS: Reasons behind the decrease in Western countries could potentially be related to the overall improvements in global health; the possible contribution of suicide prevention activities remains unclear. Increases in several South American countries might be related to economic recession and its impact on adolescents from diverse cultural backgrounds, and partly also to improvements in mortality registration. PMID- 26559742 TI - Search Engine Ranking, Quality, and Content of Web Pages That Are Critical Versus Noncritical of Human Papillomavirus Vaccine. AB - PURPOSE: Online information can influence attitudes toward vaccination. The aim of the present study was to provide a systematic evaluation of the search engine ranking, quality, and content of Web pages that are critical versus noncritical of human papillomavirus (HPV) vaccination. METHODS: We identified HPV vaccine related Web pages with the Google search engine by entering 20 terms. We then assessed each Web page for critical versus noncritical bias and for the following quality indicators: authorship disclosure, source disclosure, attribution of at least one reference, currency, exclusion of testimonial accounts, and readability level less than ninth grade. We also determined Web page comprehensiveness in terms of mention of 14 HPV vaccine-relevant topics. RESULTS: Twenty searches yielded 116 unique Web pages. HPV vaccine-critical Web pages comprised roughly a third of the top, top 5- and top 10-ranking Web pages. The prevalence of HPV vaccine-critical Web pages was higher for queries that included term modifiers in addition to root terms. Compared with noncritical Web pages, Web pages critical of HPV vaccine overall had a lower quality score than those with a noncritical bias (p < .01) and covered fewer important HPV-related topics (p < .001). Critical Web pages required viewers to have higher reading skills, were less likely to include an author byline, and were more likely to include testimonial accounts. They also were more likely to raise unsubstantiated concerns about vaccination. CONCLUSIONS: Web pages critical of HPV vaccine may be frequently returned and highly ranked by search engine queries despite being of lower quality and less comprehensive than noncritical Web pages. PMID- 26559743 TI - Passive acoustic monitoring of beaked whale densities in the Gulf of Mexico. AB - Beaked whales are deep diving elusive animals, difficult to census with conventional visual surveys. Methods are presented for the density estimation of beaked whales, using passive acoustic monitoring data collected at sites in the Gulf of Mexico (GOM) from the period during and following the Deepwater Horizon oil spill (2010-2013). Beaked whale species detected include: Gervais' (Mesoplodon europaeus), Cuvier's (Ziphius cavirostris), Blainville's (Mesoplodon densirostris) and an unknown species of Mesoplodon sp. (designated as Beaked Whale Gulf - BWG). For Gervais' and Cuvier's beaked whales, we estimated weekly animal density using two methods, one based on the number of echolocation clicks, and another based on the detection of animal groups during 5 min time-bins. Density estimates derived from these two methods were in good general agreement. At two sites in the western GOM, Gervais' beaked whales were present throughout the monitoring period, but Cuvier's beaked whales were present only seasonally, with periods of low density during the summer and higher density in the winter. At an eastern GOM site, both Gervais' and Cuvier's beaked whales had a high density throughout the monitoring period. PMID- 26559745 TI - Lower blood pressure targets: to whom do they apply? PMID- 26559744 TI - Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. AB - BACKGROUND: Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure lowering strategies. METHODS: For this updated systematic review and meta analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. FINDINGS: We identified 19 trials including 44,989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3.8 years of follow-up (range 1.0-8.4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4-22]), myocardial infarction (13% [0-24]), stroke (22% [10-32]), albuminuria (10% [3-16]), and retinopathy progression (19% [0-34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI -11 to 34]), cardiovascular death (9% [-11 to 26]), total mortality (9% [-3 to 19]), or end-stage kidney disease (10% [ 6 to 23]). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1.2% per year in intensive blood pressure-lowering group participants, compared with 0.9% in the less intensive treatment group (RR 1.35 [95% CI 0.93-1.97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2.68 [1.21-5.89], p=0.015), but the absolute excess was small (0.3% vs 0.1% per person year for the duration of follow-up). INTERPRETATION: Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. FUNDING: National Health and Medical Research Council of Australia. PMID- 26559746 TI - Dual-polarity metamaterial circular polarizer based on giant extrinsic chirality. AB - Chirality is ubiquitous in nature. The associated optical activity has received much attention due to important applications in spectroscopy, analytical chemistry, crystallography and optics, however, artificial chiral optical materials are complex and difficult to fabricate, especially in the optical range. Here, we propose an ultrathin dual-polarity metamaterial circular polarizer by exploiting the mechanism of giant extrinsic chirality. The polarity of the circular polarizer with large suppression of linear anisotropy can be switched by changing the sign of incident angle. The microwave experiments and optical simulations demonstrate that the large angle of incidence facilitates the high-efficiency circular polarizer, which can be realized in the whole spectra from microwave to visible frequencies. The ultrathin single-layer metamaterials with extrinsic chirality will be a promising candidate for circular polarization devices. PMID- 26559747 TI - Surgical results and psychological status in patients with intractable Meniere's disease. AB - OBJECTIVES: Mental disorder is often one of the causes to make treatments for Meniere's disease more difficult. The aim in the present study is to examine ratios of the neurosis and depression in patients with intractable Meniere's disease and also relationships between the ratios and surgical results after endolymphatic sac drainage with large doses of steroids. METHODS: Between 1998 and 2009, we enrolled 263 intractable Meniere's patients and divided into two groups, 207 in surgical group and 56 in non-surgical group. We used the Cornell Medical Index (CMI) and the Self-rating Depression Scale (SDS) at the diagnosis in our hospital to evaluate their psychological condition before treatments. CMI domains III and IV were defined as neurosis and SDS scores more than 40 as depression as a matter of convenience. Two years as well as seven years after surgery, patients with vertigo zero/month and hearing change>-10dB were evaluated in success group and the others in non-success group. RESULTS: Neurosis and depression were diagnosed in approximately 40% and 60%, respectively, of intractable Meniere's disease. Our results showed that surgical treatment significantly improved vertigo suppression and hearing gain in patients with no psychological symptoms compared with those exhibiting psychological symptoms both in surgical and non-surgical groups. Furthermore, surgical results in cases with mental disorder were superior to non-surgical results in cases without mental distress. CONCLUSIONS: All taken together, psychological supports could be necessary for improving results both in the surgical and non-surgical treatments for patients with intractable Meniere's disease. Some cases with intractable Meniere's disease should really require additional surgical treatments even after psychological therapies. PMID- 26559748 TI - Risk factors for sleep impairment in adult patients with chronic rhinosinusitis. AB - OBJECTIVE: Although sleep impairment is reported by patients with chronic rhinosinusitis, the associated factors have not been well studied. Therefore, we determined the associated risk factors for sleep impairment in patients with chronic rhinosinusitis (CRS). METHODS: This study was a prospective cohort study. A total of 572 adult patients (171 women, 401 men; mean age, 49.0 years; range, 18-64 years) who completed a questionnaire, had a clinical examination, and underwent endoscopic sinus surgery were analyzed using stepwise multiple linear regression. RESULTS: With regard to subjective symptoms, nasal obstruction (beta coef., 0.27; p<0.001), anterior nasal drainage (beta coef., 0.13; p=0.004), facial pain/pressure (beta coef., 0.09; p=0.048), headache (beta coef., 0.10; p=0.010), and cough (beta coef., 0.14; p<0.001) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.240; p=0.048). In the matter of background parameters, total polyp score (polyp grading system) (beta coef., 0.16; p<0.001) and allergic rhinitis (beta coef., 0.09; p=0.034) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.029; p=0.034). CONCLUSION: These results suggest that sleep impairment in these patients is caused by the various mechanisms associated with nasal symptoms themselves, CRS and allergic rhinitis. However, the specific pathophysiology has not been clarified yet; further studies are expected to elucidate that of sleep impairment in patients with CRS. PMID- 26559749 TI - Time for authors of paper to write to health secretary over misuse of weekend mortality data? PMID- 26559750 TI - APOBEC3H polymorphisms and susceptibility to HIV-1 infection in an Indian population. AB - Human APOBEC3H (A3H) is a member of APOBEC cytidine deaminase family intensively constraining the HIV-1 replication. A3H is known to be polymorphic with different protein stability and anti-HIV-1 activity in vitro. We recently reported that A3H haplotypes composed of two functional polymorphisms, rs139292 (N15del) and rs139297 (G105R), were associated with the susceptibility to HIV-1 infection in Japanese. To confirm the association of A3H and HIV-1 infection in another ethnic group, a total of 241 HIV-1-infected Indian individuals and ethnic-matched 286 healthy controls were analyzed for the A3H polymorphisms. The frequency of 15del allele was high in the HIV-1-infected subjects as compared with the controls (0.477 vs 0.402, odds ratio (OR)=1.36, P=0.014). Haplotype analysis showed that the frequencies of 15del-105R was high (0.475 vs 0.400, OR=1.36, permutation P=0.037) in the HIV-1-infected subjects, confirming the association of A3H polymorphisms with the susceptibility to HIV-1 infection. PMID- 26559751 TI - A de novo mosaic mutation of PHEX in a boy with hypophosphatemic rickets. AB - X-linked dominant hypophosphatemic rickets (XLHR), is characterized mainly by renal phosphate wasting with hypophosphatemia, short stature and abnormal bone mineralization. PHEX, located at Xp22.1-p22.2, is the gene causing XLHR. We aim to characterize the pathogenesis of a Chinese boy who is apparently 'heterozygous' in PHEX gene. Direct sequencing showed two peaks: one was a wild type 'G' and the other was one base substitution to 'A', though the patient was a male. TA clone assay clearly showed each sequences and the ratios. The mutation effect was predicted via bioinformatics and validated by exon-trapping assay. Real-time PCR was applied to determine the copy number of PHEX. TA clone assay showed the frequency of normal (G) to mutant allele (A) as 19:13. Normal karyotype and real-time PCR results indicate the normal copy number of PHEX. This splice site mutation leads to 4 bp of exon 18 skipping out causing frame shift p.Gly590Glufs*28 that ends up with a loss of active site and Zn(2+)-binding site of PHEX, which probably interfere with renal phosphate reabsorption and bone mineralization. In conclusion, mutation at conserved splice acceptor site resulted in aberrant splicing, ending up with a damaged protein product. This novel mutation is de novo in mosaic pattern that may be induced during early postzygotic period. Taking mosaic somatic mutation of PHEX into consideration is strongly suggested in genetic counseling and etiology research for XLHR. PMID- 26559752 TI - Six-layer structure for genomics and its applications. AB - The term 'genetics' was coined before an understanding of DNA sequence data was achieved, and it is now insufficient to describe the broad areas in which DNA data have important roles. The term genomics is more broadly descriptive, but it does not provide a satisfactory conceptual framework that scientists can share. Here I propose a six-layer structure that describes the entire scientific field for 'genomics'. The proposed layers are 'life' as the uppermost layer, followed by 'species', 'population', 'family', 'individual' and finally 'cell' as the bottommost layer. In each pair of adjacent layers, each member of the upper layer comprises a set of members of the lower layer. In each layer, we can define consistent partial orders of members based on genomic data in the forms of phylogenic and pedigree trees. Although total orders such as those defined for time and space in physics cannot be defined in biology, defining consistent partial orders allows mathematical analysis to be performed. I will show that mathematical genetics studies can be understood as attempts to bridge gaps between layers of the proposed six-layer structure, while genetic tests can be understood as procedures to differentiate among members of each layer by using genomic data. PMID- 26559753 TI - Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure. AB - Cluster headache (CH) is a debilitating, severe form of headache. A novel non systemic therapy has been developed that produces therapeutic electrical stimulation to the sphenopalatine ganglion (SPG). A transoral surgical technique for inserting the Pulsante SPG Microstimulator into the pterygopalatine fossa (PPF) is presented herein. Technical aspects include detailed descriptions of the preoperative planning using computed tomography or cone beam computed tomography scans for presurgical digital microstimulator insertion into the patient-specific anatomy and intraoperative verification of microstimulator placement. Surgical aspects include techniques to insert the microstimulator into the proper midface location atraumatically. During the Pathway CH-1 and Pathway R-1 studies, 99 CH patients received an SPG microstimulator. Ninety-six had a microstimulator placed within the PPF during their initial procedure. Perioperative surgical sequelae included sensory disturbances, pain, and swelling. Follow-up procedures included placement of a second microstimulator on the opposite side (n=2), adjustment of the microstimulator lead location (n=13), re-placement after initial unsuccessful placement (n=1), and removal (n=5). This SPG microstimulator insertion procedure has sequelae comparable to other oral cavity procedures including tooth extractions, sinus surgery, and dental implant placement. Twenty-five of 29 subjects (86%) completing a self-assessment questionnaire indicated that the surgical effects were tolerable and 90% would make the same decision again. PMID- 26559754 TI - 'Emotional' does not even start to cover it: Generalization of overeating in emotional eaters. AB - Based on recent studies indicating that emotional eating is not the clearly defined problem it is often thought to be, the present study investigated whether emotional eaters overeat merely in response to negative emotional cues, or to other cues as well. It was hypothesized that emotional eaters would overeat after a variety of food cues, not limited to negative emotions. Participants took part in four conditions (negative mood manipulation, positive mood manipulation, food exposure and a control condition) divided over two sessions. Each condition was followed by a bogus taste test, after which food intake was measured. Results showed strong correlations between food intake after all four conditions, indicating that increased intake after one type of cue is related to increased intake after other cues. Participants were identified as emotional or non emotional eaters based on food intake in the negative mood condition, and based on self-reported emotional eating scores. Both measures of emotional eating were significantly related to food intake after all cues. Based on the current findings, we conclude that individuals who show increased food intake when in a negative emotional state also overeat when experiencing other food-signalling cues. This indicates that 'emotional eating' may not fully capture the eating behaviour of individuals currently identified as 'emotional eaters'. PMID- 26559755 TI - Activation of TGF-beta1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis. AB - Activation of hepatic stellate cells (HSCs) by transforming growth factor-beta1 (TGF-beta1) initiates HBV-associated fibrogenesis. The mechanism of TGF-beta1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-beta1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-beta1/Smad4 was determined using dual luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-beta1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF beta1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-beta1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up regulated alpha-SMA, collagen I, and TGF-beta1 synthesis. These findings indicate that TGF-beta1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-beta receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis. PMID- 26559756 TI - Serum levels of TGF-beta1 in patients of diabetic peripheral neuropathy and its correlation with nerve conduction velocity in type 2 diabetes mellitus. AB - AIMS: To correlate serum levels of TGF-beta1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus MATERIALS AND METHODS: The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-beta1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study RESULTS: In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-beta1 showed positive correlation with nerve conduction velocities CONCLUSION: High level of TGF-beta1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. PMID- 26559757 TI - Tetralogy of Fallot and the rubber heart model: Does the rubber meet the road? PMID- 26559758 TI - Making the most of peer review. PMID- 26559759 TI - Significance of left atrial appendage filling defects on cardiac CT prior to pulmonary vein isolation for atrial fibrillation. PMID- 26559760 TI - Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers. PMID- 26559761 TI - Pentoxifylline: An effective therapy for necrobiosis lipoidica. AB - Necrobiosis lipoidica (NL) is a rare chronic inflammatory granulomatous skin disorder that remains challenging to treat. Here we report three patients at different stages of disease successfully treated with pentoxifylline, a haemorrheological and anti-inflammatory agent. We demonstrate for the first time that early stage NL may be completely reversible with this treatment. Our findings are also consistent with previous isolated reports showing the effectiveness of pentoxifylline in treating ulcerative NL. PMID- 26559762 TI - Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. AB - BACKGROUND: Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival. AIM: To evaluate biochemical profiles, liver-related outcomes and adverse events following fenofibrate therapy in PBC patients with incomplete response to ursodeoxycholic acid (UDCA). METHODS: A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates and UDCA (FF) or UDCA alone, adjusted for a propensity score to account for treatment selection bias. RESULTS: A total of 120 patients were included (FF group n = 46, UDCA group n = 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase <=1.67 times the upper limit of normal] in the FF and UDCA groups, respectively (P = 0.0001). Fenofibrate was also associated with improved decompensation-free and transplant free survival [hazard ratio (HR) 0.09, 95% CI 0.03-0.32, P = 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR 0.40, 95% CI 0.17-0.93, P = 0.03). Twenty-two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in the FF group (P = 0.005). CONCLUSIONS: Fenofibrate therapy is associated with significant improvement in alkaline phosphatase, decompensation free and transplant-free survival in PBC patients with incomplete UDCA response. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity of alkaline phosphatase as an appropriate response criteria for fibrate therapy. PMID- 26559763 TI - Central memory CD4+ T cells are preferential targets of double infection by HIV 1. AB - BACKGROUND: Template switching between two distinct HIV-1 RNA genomes during reverse transcription gives rise to recombinant viruses that greatly expand the genetic diversity of HIV-1 and have adverse implications for drug resistance, immune escape, and vaccine design. Virions with two distinct genomes are produced exclusively from cells infected with two or more viruses, or 'doubly infected' cells. Previous studies have revealed higher than expected frequencies of doubly infected cells compared to frequencies based on chance alone, suggesting non random enhancement of double infection. METHODS: We investigated double infection of unstimulated primary CD4+ T cells using reporter viruses carrying genes for different fluorescent proteins, EGFP and mCherry, combined with sophisticated modeling techniques based on Poisson distribution. Additionally, through the use of multiparameter flow cytometry we examined the susceptibility of naive and memory subsets of CD4+ T cells to double infection by HIV. RESULTS: Using our double infection system, we confirm non-random enhancement of multiple infection events. Double infection of CD4+ T cells was not found to be a consequence of suboptimal provirus expression rescued by Tat in trans-as has been reported in cell lines-but rather due to a heterogeneous cell population in which only a fraction of primary peripheral blood CD4+ T cells are susceptible to HIV infection regardless of viral titer. Intriguingly, double infection of CD4+ T cells occurred preferentially in memory CD4+ T cells-particularly the central memory (TCM) subset-but was not a consequence of SAMHD1-mediated restriction of HIV infection in naive cells. CONCLUSIONS: These findings reveal that double infection in primary CD4+ T cells is primarily a consequences of cellular heterogeneity and not rescue of suboptimal provirus expression by Tat in trans. Additionally, we report a previously unappreciated phenomenon of enhanced double infection within primary TCM cells and suggest that these long-lived cells may serve as an archive that drive ongoing viral recombination events in vivo. PMID- 26559764 TI - Use of next generation sequencing data to develop a qPCR method for specific detection of EU-unauthorized genetically modified Bacillus subtilis overproducing riboflavin. AB - BACKGROUND: Recently, the presence of an unauthorized genetically modified (GM) Bacillus subtilis bacterium overproducing vitamin B2 in a feed additive was notified by the Rapid Alert System for Food and Feed (RASFF). This has demonstrated that a contamination by a GM micro-organism (GMM) may occur in feed additives and has confronted for the first time,the enforcement laboratories with this type of RASFF. As no sequence information of this GMM nor any specific detection or identification method was available, Next GenerationSequencing (NGS) was used to generate sequence information. However, NGS data analysis often requires appropriate tools, involving bioinformatics expertise which is not alwayspresent in the average enforcement laboratory. This hampers the use of this technology to rapidly obtain critical sequence information in order to be able to develop a specific qPCRdetection method. METHODS: Data generated by NGS were exploited using a simple BLAST approach. A TaqMan(r) qPCR method was developed and tested on isolated bacterial strains and on the feed additive directly. RESULTS: In this study, a very simple strategy based on the common BLAST tools that can be used by any enforcement lab without profound bioinformatics expertise, was successfully used toanalyse the B. subtilis data generated by NGS. The results were used to design and assess a new TaqMan(r) qPCR method, specifically detecting this GM vitamin B2 overproducing bacterium. The method complies with EU critical performance parameters for specificity, sensitivity, PCR efficiency and repeatability. The VitB2-UGM method also could detect the B. subtilis strain in genomic DNA extracted from the feed additive, without prior culturing step. CONCLUSIONS: The proposed method, provides a crucial tool for specifically and rapidly identifying this unauthorized GM bacterium in food and feed additives by enforcement laboratories. Moreover, this work can be seen as a case study to substantiate how the use of NGS data can offer an added value to easily gain access to sequence information needed to develop qPCR methods to detect unknown andunauthorized GMO in food and feed. PMID- 26559765 TI - SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia. AB - BACKGROUND: In addition to genetic and epigenetic alteration, post-translational modification of proteins plays a critical role in the initiation, progression and maturation of acute myeloid leukemia (AML). METHODS: The SUMOylation site of sPRDM16 at K568 was mutated to arginine by site-directed mutagenesis. THP-1 acute myeloid leukemia cells were transduced with a lentivirus containing wild type or K568 mutant sPRDM16. Proliferation, self-renewal and differentiation of transduced THP-1 cells were analyzed both in vitro cell culture and in mouse xenografts. Gene expression profiles were analyzed by RNA-seq. RESULTS: Overexpression of sPRDM16 promoted proliferation, enhanced self-renewal capacity, but inhibited differentiation of THP-1 acute myeloid leukemia cells. We further confirmed that K568 is a bona fide SUMOylation site on sPRDM16. Mutation of the sPRDM16 SUMOylation site at K568 partially abolished the capacity of sPRDM16 to promote proliferation and inhibit differentiation of acute myeloid leukemia cells both in vitro and in mouse xenografts. Furthermore, THP-1 cells overexpressing sPRDM16-K568R mutant exhibited a distinct gene expression profile from wild type sPRDM16 following incubation with PMA. CONCLUSIONS: Our results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia. PMID- 26559766 TI - Pediatric emergence delirium: Canadian Pediatric Anesthesiologists' experience. AB - INTRODUCTION: Pediatric emergence agitation/delirium (ED) is a cluster of behaviors seen in the early postanesthetic period with negative emotional consequences for families and increased utilization of healthcare resources. Many studies have looked at identifying risk factors for ED and at pharmacologic regimens to prevent ED. There are few published reports on treatment options and efficacy for established ED episodes, and essentially no data concerning current practice in the treatment of ED. We sought to elicit the experience and opinions of Canadian Pediatric Anesthesiologists on the incidence of ED in their practice, definitions and diagnostic criteria, preventative strategies, treatments, and their perceived efficacy. METHODS: A web-based survey was sent to pediatric anesthesiologists working at academic health science centers across Canada. The participants were selected based on being members of the Canadian Pediatric Anesthesia Society (CPAS), which represents the subspecialty in Canada. All members of CPAS who had e-mail contact information available in the membership database were invited to participate. A total of 209 members out of the total of 211 fulfilled these criteria and were included in the study population. RESULTS: The response rate was 51% (106/209). Of respondents, 42% felt that ED was a significant problem at their institutions, with 45% giving medication before or during anesthesia to prevent the development of ED. Propofol was the most common medication given to prevent ED (68%) and to treat ED (42%). Total intravenous anesthesia (TIVA) was considered by 38% of respondents as a technique used to prevent ED. Medications used for treatment included propofol (42%), midazolam (31%), fentanyl (10%), morphine (7%), and dexmedetomidine (5%), with 87% of respondents rating effectiveness of treatment as 'usually works quickly with one dose'. DISCUSSION: We present information on current practice patterns with respect to prophylaxis and treatment of ED among a specialized group of pediatric anesthesiologists and highlight the importance of further research in improving the treatment of this common and challenging peri-anesthetic occurrence. PMID- 26559776 TI - The lung cancer breath signature: a comparative analysis of exhaled breath and air sampled from inside the lungs. AB - Results collected in more than 20 years of studies suggest a relationship between the volatile organic compounds exhaled in breath and lung cancer. However, the origin of these compounds is still not completely elucidated. In spite of the simplistic vision that cancerous tissues in lungs directly emit the volatile metabolites into the airways, some papers point out that metabolites are collected by the blood and then exchanged at the air-blood interface in the lung. To shed light on this subject we performed an experiment collecting both the breath and the air inside both the lungs with a modified bronchoscopic probe. The samples were measured with a gas chromatography-mass spectrometer (GC-MS) and an electronic nose. We found that the diagnostic capability of the electronic nose does not depend on the presence of cancer in the sampled lung, reaching in both cases an above 90% correct classification rate between cancer and non-cancer samples. On the other hand, multivariate analysis of GC-MS achieved a correct classification rate between the two lungs of only 76%. GC-MS analysis of breath and air sampled from the lungs demonstrates a substantial preservation of the VOCs pattern from inside the lung to the exhaled breath. PMID- 26559777 TI - Efficacy of pectoralis major muscle flap for pharyngocutaneous fistula prevention in salvage total laryngectomy: A systematic review. AB - BACKGROUND: The role of pectoralis major muscle flap (PMMF) in reducing the rate of pharyngocutaneous fistula after salvage total laryngectomy has not been clearly established. The purpose of this study was to evaluate the impact of PMMF in reducing pharyngocutaneous fistula rates after total laryngectomy. METHODS: The analyzed intervention was the use of a PMMF after total laryngectomy. RESULTS: Pharyngocutaneous fistula occurred in 230 cases (global incidence, 30.9%). In the group of patients who underwent PMMFs, there were 49 cases of pharyngocutaneous fistula, compared with 181 cases in the control group. There was a 22% decreased risk of pharyngocutaneous fistula incidence in the PMMF group (p < .001). Patients who underwent a PMMF had lower risk of pharyngocutaneous fistula compared with the control group (p = .008). There were no changes when only patients who underwent total laryngectomy (p < .001) and those who underwent total pharyngolaryngectomy (p = .007) were separately assessed. CONCLUSION: Prophylactic use of PMMF decreases the incidence of pharyngocutaneous fistula after salvage total laryngectomy. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E2317-E2321, 2016. PMID- 26559778 TI - A trait-based metric sheds new light on the nature of the body size-depth relationship in the deep sea. AB - Variation within species is an often-overlooked aspect of community ecology, despite the fact that the ontogenetic structure of populations influences processes right up to the ecosystem level. Accounting for traits at the individual level is an important advance in the implementation of trait-based approaches in understanding community structure and function. We incorporate individual- and species-level traits into one succinct assemblage structure metric, fractional size, which is calculated as the length of an individual divided by its potential maximum length. We test the implementation of fractional size in demersal fish assemblages along a depth gradient in the deep sea. We use data from an extensive trawl survey at depths of 300-2030 m on the continental slope of the Rockall Trough, Northeast Atlantic, to compare changes in fractional size structure along an environmental gradient to those seen using traditional taxonomic and trait-based approaches. The relationship between fractional size and depth was particularly strong, with the overall pattern being an increase with depth, implying that individuals move deeper as they grow. Body size increased with depth at the intraspecific and assemblage levels. Fractional size, size structure and species composition all varied among assemblages, and this variation could be explained by the depth that the assemblage occupied. The inclusion of individual-level traits and population fractional size structure adds to our understanding at the assemblage level. Fractional size, or where an individual is in its growth trajectory, appears to be an especially important driver of assemblage change with depth. This has implications for understanding fisheries impacts in the deep sea and how these impacts may propagate across depths. PMID- 26559779 TI - Splenic abscess in cancer chemotherapy. AB - BACKGROUND: Splenic abcess is an uncommon complication for cancer treatment. It occurs more frequently in immunocompromised patients. They are characterized by high mortality. The classic triad (fever, pain of the left hypochondrium, and sensitive mass left) is only present in one-third of cases the clinical spectrum ranging from no symptoms to events such as fever, nausea, vomiting, weight loss, abdominal pain left, splenomegaly. Treatment options are limited, but must be discussed and adapted to the patient profile. CASE PRESENTATION: We report the case of a 62-year-old Arabic male, diagnosed with metastatic lung adenocarcinoma, who, after several cycles of chemotherapy, presented symptoms and signs of splenic abcess. CONCLUSION: Splenic abcess is rare situation, which must be actively researched, to have access to an optimal therapeutic approach. PMID- 26559780 TI - Single-incision Laparoscopic Appendectomy Versus Conventional Laparoscopic Appendectomy: Experiences From 1208 Cases of Single-incision Laparoscopic Appendectomy. Experiences From 1208 Cases of Single-incision Laparoscopic Appendectomy. AB - OBJECTIVE: Currently single-incision laparoscopic appendectomy (SIL-A) has become an option for treating appendicitis. The aim of this study was to evaluate the safety and feasibility of SIL-A compared with conventional laparoscopic appendectomy (CL-A) on a large experimental cohort. BACKGROUND: Several studies had reported the safety and technical feasibility of SIL-A, albeit with a limited number of study subjects. METHODS: A total of 2587 patients (1208 SIL-A and 1379 CL-A) who underwent laparoscopic appendectomy from May 2008 to April 2013 were studied retrospectively. The clinical characteristics and short-term operative outcomes of these patients were reviewed and analyzed. RESULTS: There were more simple type appendicitis in the SIL-A group and more complicated type appendicitis in CL-A group (81.0% vs 74.7% and 19% vs 25.3%, P <0.001, respectively). The operative time (minutes) was similar between the 2 groups (40.1 +/- 18.6 vs 38.8 +/- 25.2, P = 0.154). However, on subgroup analysis, operative time for simple type appendicitis was longer in the SIL-A group (36.6 +/- 14.9 vs 32.3 +/- 18.3, P < 0.001). The superficial incisional surgical site infection rate was higher in the SIL-A group (4.4% vs 2.3%, P = 0.003). The readmission rate was higher in the CL-A group (0.8% vs 1.7%, P = 0.042). The postoperative hospital stay (days) was shorter in the SIL-A group (3.05 +/- 1.97 vs 3.35 +/- 2.14, P < 0.001). CONCLUSIONS: In this study, SIL-A was technically feasible and safe option for appendicitis. The SIL-A group had more favorable outcomes such as shorter time to start diet and less hospital stay after surgery than the CL-A group. However, superficial incisional surgical site infection rate was higher in the SIL-A group than in the CL-A group, an effort to reduce superficial incisional SSI should be made. PMID- 26559781 TI - Reply to Letter: "When the Patient Is Sicker Than His Liver". PMID- 26559783 TI - Trends in Mortality of Congenital Heart Defects. AB - OBJECTIVE: The aim of the present nationwide cohort study was to describe trends in 1-year mortality in live-born children with congenital heart defects in Norway 1994-2009 and to assess whether changes in the proportion of terminated pregnancies and altered operative mortality have influenced these trends. METHODS: Medical information concerning all 954 413 live births, stillbirths, and late-term abortions in Norway, 1994-2009, was retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry for Congenital Heart Defects and the Norwegian Cause of Death Registry. Survivors were followed through 2012. RESULTS: The 1-year cumulative mortality proportion during the study period was 17.4% for children with severe congenital heart defects and 3.0% for children with nonsevere congenital heart defects. The 1-year cumulative mortality proportion among live born children with severe congenital heart defects decreased 3.6% (95% CI: -5.4, -1.5) per year. The total mortality of severe congenital heart defects was unchanged when including stillbirths and late-term abortions with severe congenital heart defects. The proportion of stillbirths or terminated pregnancies with severe congenital heart defects among all pregnancies with severe congenital heart defects, was on average 8.8% over the entire period with an annually increase of 16.6% (11.4, 18.0). The mean operative mortality in children with severe congenital heart defects was 8.4% and decreased by 9.0% (-11.9, -5.9) per year. CONCLUSIONS: The 1-year mortality of severe congenital heart defects among live births, 1994-2009, declined in Norway. The downward trend in mortality may be explained by a more frequent use of termination of affected pregnancies, and the reduced operative mortality of severe congenital heart defects. PMID- 26559784 TI - Roseovarius atlanticus sp. nov., isolated from surface seawater. AB - A taxonomic study was carried out on strain R12BT, which was isolated from surface seawater of the Atlantic Ocean. The bacterium was observed to be rod shaped, Gram-stain-negative, oxidase-positive and weakly positive for catalase. Growth was observed at salinities of 0.5-15 % and at temperatures of 4-45 degrees C. The isolate was incapable of nitrate reduction and hydrolysis of gelatin, Tween 80 and aesculin. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain R12BT belonged to the genus Roseovarius, with highest sequence similarity to Roseovarius indicus B108T (97.2 % 16S rRNA gene sequence similarity), followed by Roseovarius halotolerans HJ50T (96.8 %); other species of genus Roseovarius shared 93.0-96.2 % sequence similarities. The DNA DNA hybridization estimate value between strain R12BT and R. indicus B108T was 23.2 +/- 2.4 %. The average nucleotide identity between strain R12BT and R. indicus B108T was 77.1 %. The principal fatty acids were summed feature 8 (C18 : 1omega7c/omega6c) and C16 : 0. The G+C content of the chromosomal DNA was 63.6 mol%. The respiratory quinone was determined to be Q-10. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, two aminolipids, two phospholipids and some unidentified lipids were present. The combined genotypic and phenotypic data show that strain R12BT represents a novel species of the genus Roseovarius, for which the name Roseovarius atlanticus sp. nov. is proposed, with the type strain R12BT ( = MCCC 1A09786T = KCTC 42506T). PMID- 26559782 TI - Molecular mechanisms of suberoylanilide hydroxamic acid in the inhibition of TGF beta1-mediated canine corneal fibrosis. AB - OBJECTIVE: To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-beta1, as well as matrix metalloproteinase (MMP) activity. METHODS: Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-beta1 (5 ng/mL) and SAHA (2.5 MUm) for 24 h. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2, and JNK1. Real time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8, and MMP9 mRNA expressions and MMP2 and MMP9 protein activities, respectively. RESULTS: TGF beta1 treatment caused a significant increase in phospho-Smad2/3 and phospho-p38 MAPK. SAHA treatment reduced TGF-beta1-induced phosphorylation of Smad2/3 but not of p38 MAPK. TGF-beta1 did not modulate the phosphorylation of ERK1/2 or JNK1. SAHA caused a significant reduction in phospho-ERK1/2 expression regardless of concurrent TGF-beta1 treatment. Neither SAHA alone nor in combination with TGF beta1 altered phospho-JNK1 expression. TGF-beta1 significantly increased MMP1 and MMP9 mRNA expressions but did not alter MMP2 mRNA. SAHA treatment attenuated TGF beta1-induced MMP9 mRNA expression while significantly enhancing TGF-beta1 induced MMP1 mRNA expression. Zymography detected reduced expression of MMP2 and MMP9 proteins in untreated control CCF. TGF-beta1 treatment did not alter their expression, but SAHA treatment +/-TGF-beta1 significantly increased MMP2 and MMP9 protein expressions. CONCLUSIONS: The corneal anti-fibrotic effects of SAHA involve multiple mechanisms including modulation of canonical and non-canonical components of TGF-beta1 intracellular signaling and MMP activity. PMID- 26559785 TI - Electrochemical Insight into the Brust-Schiffrin Synthesis of Au Nanoparticles. AB - The mechanism of the Brust-Schiffrin gold nanoparticle synthesis has been investigated through the use of ion transfer voltammetry at the water/1,2 dichloroethane (DCE) solution interface, combined with X-ray absorption fine structure (XAFS) of the reaction between [AuCl4](-) and thiol (RSH) in homogeneous toluene (TL) solution. Ion transfer calculations indicate the formation of [AuCl2](-) at RSH/Au ratios from 0.2-2 with a time-dependent variation observed over several days. At RSH/Au ratios above 2 and after time periods greater than 24 h, the formation of Au(I)SR is also observed. The relative concentrations of reaction products observed at the liquid/liquid interface are in excellent agreement with those observed by XAFS for the corresponding reaction in a single homogeneous phase. BH4(-) ion transfer reactions between water and DCE indicate that the reduction of [AuCl4](-) or [AuCl2](-) to Au nanoparticles by BH4(-) proceeds in the bulk organic phase. On the other hand, BH4(-) was unable to reduce the insoluble [Au(I)SR]n species to Au nanoparticles. The number and size of the nanoparticles formed was dependent on the concentration ratio of RSH/Au, as well as the experimental duration because of the competing formation of the [Au(I)SR]n precipitate. Higher concentrations of nanoparticles, with diameters of 1.0-1.5 nm, were formed at RSH/Au ratios from 1 to 2. PMID- 26559787 TI - Companion diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC. AB - The immune checkpoint inhibitors pembrolizumab and nivolumab together with their diagnostic assays have recently been granted market authorization for treatment of advanced non-small-cell lung cancer in the USA. The two assays, PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx (both by Dako, Glostrup, Denmark), are the first PD-L1 IHC assays to obtain regulatory approval through the Premarket Approval process. This approval is supported by recent clinical studies that have shown a positive correlation between PD-L1 expression and the outcome following treatment with different PD-1/PD-L1 checkpoint inhibitors. These diagnostic assays are able to identify the group of non-small-cell lung cancer patients who will benefit most from treatment with the immune checkpoint inhibitors. However, so far, it is only the PD-L1 IHC 22C3 pharmDx assay, which is linked to the use of pembrolizumab, that has obtained regulatory status as a companion diagnostic. PMID- 26559786 TI - Altered Striatal Synaptic Function and Abnormal Behaviour in Shank3 Exon4-9 Deletion Mouse Model of Autism. AB - Shank3 is a multi-domain, synaptic scaffolding protein that organizes proteins in the postsynaptic density of excitatory synapses. Clinical studies suggest that ~ 0.5% of autism spectrum disorder (ASD) cases may involve SHANK3 mutation/deletion. Patients with SHANK3 mutations exhibit deficits in cognition along with delayed/impaired speech/language and repetitive and obsessive/compulsive-like (OCD-like) behaviors. To examine how mutation/deletion of SHANK3 might alter brain function leading to ASD, we have independently created mice with deletion of Shank3 exons 4-9, a region implicated in ASD patients. We find that homozygous deletion of exons 4-9 (Shank3(e4-9) KO) results in loss of the two highest molecular weight isoforms of Shank3 and a significant reduction in other isoforms. Behaviorally, both Shank3(e4-9) heterozygous (HET) and Shank3(e4-9) KO mice display increased repetitive grooming, deficits in novel and spatial object recognition learning and memory, and abnormal ultrasonic vocalizations. Shank3(e4-9) KO mice also display abnormal social interaction when paired with one another. Analysis of synaptosome fractions from striata of Shank3(e4-9) KO mice reveals decreased Homer1b/c, GluA2, and GluA3 expression. Both Shank3(e4-9) HET and KO demonstrated a significant reduction in NMDA/AMPA ratio at excitatory synapses onto striatal medium spiny neurons. Furthermore, Shank3(e4-9) KO mice displayed reduced hippocampal LTP despite normal baseline synaptic transmission. Collectively these behavioral, biochemical and physiological changes suggest Shank3 isoforms have region-specific roles in regulation of AMPAR subunit localization and NMDAR function in the Shank3(e4-9) mutant mouse model of autism. PMID- 26559788 TI - Mechanical integrity of a carbon nanotube/copper-based through-silicon via for 3D integrated circuits: a multi-scale modeling approach. AB - Carbon nanotube (CNT)/copper (Cu) composite material is proposed to replace Cu based through-silicon vias (TSVs) in micro-electronic packages. The proposed material is believed to offer extraordinary mechanical and electrical properties and the presence of CNTs in Cu is believed to overcome issues associated with miniaturization of Cu interconnects, such as electromigration. This study introduces a multi-scale modeling of the proposed TSV in order to evaluate its mechanical integrity under mechanical and thermo-mechanical loading conditions. Molecular dynamics (MD) simulation was used to determine CNT/Cu interface adhesion properties. A cohesive zone model (CZM) was found to be most appropriate to model the interface adhesion, and CZM parameters at the nanoscale were determined using MD simulation. CZM parameters were then used in the finite element analysis in order to understand the mechanical and thermo-mechanical behavior of composite TSV at micro-scale. From the results, CNT/Cu separation does not take place prior to plastic deformation of Cu in bending, and separation does not take place when standard thermal cycling is applied. Further investigation is recommended in order to alleviate the increased plastic deformation in Cu at the CNT/Cu interface in both loading conditions. PMID- 26559789 TI - Association between ordering patterns and shift-based care in general pediatrics inpatients. AB - Duty-hour restrictions have forced changes in care models for inpatient services, including an increase in shift work. In this study we aimed to determine whether a shift model compliant with 2011 Accreditation Council for Graduate Medical Education duty-hour standards was associated with more active patient care management. Residents caring for pediatric patients changed from a schedule with extended duty shifts and cross-coverage to one based on day/night shifts, limiting interns to 16 consecutive duty hours. We conducted a retrospective review of orders written under each model. After the intervention, there was a significant increase in the mean number of orders written within the first 12 hours (pre: 0.58 orders vs post: 1.12, P = 0.009) and 24 hours (pre: 1.52 vs post: 2.38, P = 0.004) following admission (not including admission orders), but we did not detect a significantly higher percentage of orders written at night. This shift-based coverage system was associated with a greater number of orders written early in the hospitalization, indicating more active management of clinical problems. PMID- 26559791 TI - Telemedicine for the management of COPD - near future or a hazy idea? PMID- 26559790 TI - Combined treatment with memantine/es-citalopram for older depressed patients with cognitive impairment: a pilot study. AB - OBJECTIVE: The objective of the study is to assess combined antidepressant and memantine treatment in older patients presenting with depression and cognitive impairment. METHODS: Thirty-five depressed patients with cognitive impairment participated in this open-label pilot study. We evaluated whether, over a 48-week period, combined antidepressant (primarily es-citalopram) and memantine treatment was effective in the treatment of cognitive impairment and depression. Neuropsychological testing was performed, and antidepressant response monitored at baseline and at the 12, 24, and 48-week time points. RESULTS: Treatment with escitalopram (mean daily dose 18.62 mg, SD 5.15) and memantine (mean daily dose 13.62 mg, SD 6.67) was associated with improvement in Hamilton Depression Rating Scale scores over the 48-week study period. Patients demonstrated significant improvement in the primary outcome of cognitive performance (Selective Reminding Test total immediate recall; SRT-IR) over the 48-week treatment period (p = 0.0147). Significant improvement was also observed in measures of naming and verbal fluency but not in the other cognitive domains. One of the 35 patients (2.9%) converted to Alzheimer's disease over the 48-week treatment period. In the amnestic mild cognitive impairment subsample (n = 22), the conversion rate was 4.5%, a rate lower than in other reports of patients with DEP-CI. CONCLUSIONS: In this open-label trial, combined antidepressant and memantine treatment in patients with DEP-CI was associated with improved cognition and a low rate of conversion to dementia compared with published studies in patients with DEP-CI. Although limited by the open-label study design that incorporates practice effects that can improve cognitive test performance, the findings suggest the need for a larger randomized placebo-controlled trial. PMID- 26559792 TI - Change is in the air: bronchial valves to improve quality of life in heterogeneous emphysema. PMID- 26559793 TI - The influence of lung volume reduction with intrabronchial valves on the quality of life of patients with heterogeneous emphysema - a prospective study. AB - INTRODUCTION: A heterogeneous emphysema is one of the most severe forms of chronic obstructive pulmonary disease (COPD). In some cases, besides the standard pharmacotherapy, a new treatment option of emphysema can be used - bronchoscopic lung volume reduction (BLVR) with the use of intrabronchial valves. OBJECTIVES: To examine the health-related quality of life (HRQoL) of patients with severe emphysema after intrabronchial valve (IBV) implantation for the treatment of one lung. MATERIAL AND METHODS: From 2011 to 2013 a single centre prospective observational study was performed. The study assessed the effect of the therapeutic BLVR intervention, measured by St. George Respiratory Questionnaire (SGRQ). A statistical analysis by use of Wilcoxon test for dependent variables was performed. RESULTS: Twenty patients were enrolled to the study (mean age 63 +/- 10 years), all ex-smokers with tobacco exposure 38 +/- 11.3 packyears. After 3 months of IBV treatment the average SGRQ score improved significantly in total (-12.8; p < 0.001) and in domains and the differences were for: "symptoms" (-8.5; p < 0.001), "activity" (-13.9; p < 0.001) and "influence on life"(-13.5; p < 0.002). CONCLUSIONS: The presented study revealed a significant improvement of the quality in the life measured by SGRQ after IBV treatment for heterogeneous emphysema. For the first time our study showed the significant improvement of all three domains of SGRQ after IBV treatment. PMID- 26559794 TI - Dynamics of body composition in male patients during chronic obstructive pulmonary disease (COPD) development. AB - INTRODUCTION: The various distribution of fat mass (FM) and lean mass (LM) during COPD development is not yet researched. MATERIAL AND METHODS: 82 male patients (40-67 years) with acute exacerbation of COPD and 19 comparable healthy males (the control group) were examined by dual-energy X-ray absorptiometry. The patients were divided into 3 groups according to COPD severity: 1st - 19 (GOLD I stage); 2nd - 43 (GOLD II) and 3rd - 20 (GOLD III). RESULTS: The patients of 3rd group had lower indices of FM, LM, bone mineral component (BMC) vs. the control and 1st, 2nd groups. A significant increase in FM share was noted in android and gynoid regions, trunk, legs and arms in 2nd groups vs. the control with the decline of these parameters in the 3rd group below the control level. A greater proportion of FM in 1st and 2nd groups was distributed in android and trunk regions vs. the control. TNF-a and leptin levels were significantly increased by 12%, 15% 17% and by 18%, 75%, 79% respectively in 1st, 2nd, 3rd groups vs. the control, while free testosterone level was lower in these groups vs. the control (by 28%, 30% and 47% respectively; p < 0,05). CONCLUSIONS: Body mass index (BMI) was within the control range in mild-moderate COPD patients in spite of LM, FM and BMC changes. The level of LM and BMC was decreased during COPD progression, while FM was increased in mild-moderate COPD and then it was decreased in severe COPD. PMID- 26559795 TI - Pilot program on distance training in spirometry testing - the technology feasibility study. AB - INTRODUCTION: Office spirometry has been widely used in recent years by general practitioners in primary care setting, thus the need for stricter monitoring of the quality of spirometry has been recognized. MATERIAL AND METHODS: A spirometry counseling network of outpatients clinics was created in Poland using portable spirometer Spirotel. The spirometry data were transferred to counseling centre once a week. The tests sent to the counseling centre were analyzed by doctors experienced in the analysis of spirometric data. In justified cases they sent their remarks concerning performed tests to the centres via e-mail. RESULTS: We received 878 records of spirometry tests in total. Data transmission via the telephone was 100% effective. The quality of spirometry tests performed by outpatients clinics was variable. CONCLUSIONS: The use of spirometers with data transfer for training purposes seems to be advisable. There is a need to proper face-to-face training of spirometry operators before an implementation of any telemedicine technology. PMID- 26559796 TI - Adherence to treatment in asthma and COPD patients in their doctors' assessment. AB - INTRODUCTION: Adherence to therapy is one of the basic preconditions of successful treatment of asthma and COPD. Unfortunately, many patients take their medication incorrectly. The aim of this study was to assess doctors' knowledge of this phenomenon, including interventions able to improve patient adherence. MATERIAL AND METHODS: It was a questionnaire-based survey conducted among convenience sample of Polish physicians treating asthma and COPD. RESULTS: One hundred and sixty one physicians, mainly specialists in allergology (44.1%) and pulmonology (37.3%) took part in the study. According to participants, asthma patients took on average 65.4 +/- 17.1% of doses of prescribed drugs, whereas COPD patients - 61.6 +/- 24.2%. Over half of respondents claimed that during the first year of treatment, no more than 20% of asthma and COPD patients discontinue their therapy. Survey participants pointed at patients discourage (41.6%) and lack of knowledge about disease (19.3%) as the main reasons for discontinuation of therapy. Almost 2/3 of participants (65.8%) claimed that they could recognize non-adherence in their patients. Prescribing combination inhaled drugs (72.7%), drugs with infrequent dosing (63.4%), and affordable ones (53.4%) were the most common interventions aimed at improving adherence provided by respondents. CONCLUSIONS: Survey participants were aware of the phenomenon of non-adherence in patients with asthma and COPD, but underestimated the real prevalence and seriousness of it. They also overestimated their ability to recognise non adherence in their patients. Therefore, not necessarily they may obtain better adherence in their asthma and COPD patients. These results point at the issues which should be addressed in pre- and postgraduate education of physicians treating chronic airways conditions. PMID- 26559797 TI - Non-high risk PE in the patients with acute or exacerbated respiratory disease: the value of the algorithm based on D-dimer evaluation and Revised Geneva Score. AB - INTRODUCTION: The diagnostic algorithm of non-high risk pulmonary embolism (PE) is based on probability scoring systems and plasma D-dimer (DD) assessment. The aim of the present study was to investigate the efficacy of Revised Geneva Scoring (RGS) and DD testing for the excluding of non-high risk PE, in the patients admitted to the hospital due to acute respiratory diseases. MATERIAL AND METHODS: The consecutive patients, above 18 years of age, referred to the department of lung diseases, entered the study. The exclusion criteria were: the pregnancy and the suspicion of high risk PE. Plasma DD was measured with quick ELISA test, VIDAS D-dimer New, bioMerieux, France. Multislice computed tomography angiography was performed in all of the patients. RESULTS: 153 patients, median age 65 (19-88) years entered the study. The probability of PE was: low - in 58 patients (38%), intermediate - in 90 (59%), high - in 5 (3%). DD < 500 ng/ml was found in 12% of patients with low and intermediate probability of PE. PE was recognized in 10 out of 153 patients (7%). None of the patients with DD < 500 ng/ml was diagnosed with PE (NPV 100%). Median DD value was significantly higher in PE patients comparing to non-PE (4500 ng/ml and 1356 ng/ml respectively, p = 0.006). CONCLUSION: In the group of the patients with acute respiratory symptoms, low or intermediate clinical probability scoring combined with normal DD had a high NPV in excluding PE. Nevertheless, such approach was not very effective, as the increased DD was noted in 88% of the examined population. PMID- 26559798 TI - Atypical image of pulmonary alveolar proteinosis - a case report. AB - Pulmonary alveolar proteinosis is a very rare interstitial lung disease caused by abnormal intra-alveolar surfactant accumulation. Usually, it appears as a "crazy paving" pattern on high-resolution computed tomography. The image is so typical, that together with the characteristic bronchoalveolar lavage examination with presence of Periodic Acid Schiff positive substance is sufficient for establishing diagnosis, without histological confirmation. We present the case of the young woman with severe dyspnoea suspected of acute hypersensitivity pneumonia. The computed tomography showed numerous intralobular nodules uniformly distributed troughout the lungs. Treatment by corticosteroids had no clinical effect and next computed tomography showed progression. Despite the high risk of complications (patient had a respiratory failure), a surgical lung biopsy was performed and the histopathological diagnosis of pulmonary alveolar proteinosis was made. The whole lung lavage procedure performed twice caused regression of radiological lesions and respiratory failure. PMID- 26559799 TI - Left brachiocephalic vein stenosis and infectious aortitis: two unusual causes of Ortner's syndrome. AB - Ortner's syndrome (also known as cardiovocal syndrome) is defined as hoarseness due to compression of the left recurrent laryngeal nerve by an enlarged left atrium or enlarged thoracic vessels. We describe two cases of Ortner's syndrome with an unusual underlying vascular pathology. In the first patient, Ortner's syndrome was a consequence of left brachiocephalic vein stenosis resulting in collateral circulation filling the aorto-pulmonary window. The second patient developed a thoracic aortic aneurysm due infectious aortitis. Both patients required careful scrutiny in differential diagnosis because of their complex past medical history and concomitant diseases. PMID- 26559800 TI - Selected molecular events in the pathogenesis of sarcoidosis - recent advances. AB - Sarcoidosis is an orphan inflammatory disorder that can virtually affect any organ or system in the body, although the lungs and lymph nodes are most frequently involved. Sarcoidosis is believed to derive from an interaction between environmental and genetic agents. Many studies emphasize a strong association between certain human leukocyte antigen (HLA) alleles and sarcoidosis susceptibility. Several new insights have allowed the further evaluation of other candidate genes with a potential function in the immunopathogenesis of sarcoidosis. This review summarizes recent advances in the identification of novel molecular markers that may play a role in different stages of disease, such as the acute phase of inflammation, granuloma formation and fibrosis. Furthermore, this article elucidates the role of both TGF-b/Smad and (HIF)-1a VEGF-ING-4 signaling pathways in the development of sarcoidosis. The potential epigenetic regulation of the processes occurring in sarcoidosis by miRNA is also discussed. PMID- 26559801 TI - Systematic review of telemonitoring in COPD: an update. AB - Telemedicine may support individual care plans in people with chronic obstructive pulmonary disease (COPD), potentially improving the clinical outcomes. To-date there is no clear evidence of benefit of telemedicine in this patients. The aim of this study is to provide an update on the effectiveness of telemedicine in reducing adverse clinical outcomes. We searched the Pubmed database for articles published between January 2005 and December 2014. We included only randomized controlled trials exclusively focused on patients with COPD and with a telemedicine intervention arm. Evaluated outcomes were number of exacerbations, ER visits, COPD hospitalizations, length of stay and death. We eventually included 12 randomized controlled trials. Most of them had a small sample size and was of poor quality, with a wide heterogeneity in the parameters and technologies used. Most studies reported a positive effect of telemonitoring on hospitalization for any cause, with risk reductions between 10% and 63%; however only three studies reached statistical significance. The same trend was observed for COPD-related hospital admission and ER visits. No significative effects of telemedicine was evidenced in reducing length of hospital stay, improving quality of life and reducing deaths. In conclusion, our study confirms that the available evidence on the effectiveness of telemedicine in COPD does not allow to draw definite conclusions; most evidence suggests a positive effect of telemonitoring on hospital admissions and ER visits. More trials with adequate sample size and with adequate consideration of background clinical services are needed to definitively establish its effectiveness. PMID- 26559802 TI - Arterial and venous thromboembolism in chronic obstructive pulmonary disease: from pathogenic mechanisms to prevention and treatment. AB - Chronic obstructive pulmonary disease (COPD) affects approximately 10% of adults older than 40 years and is an important causes of disability and death in elderly subjects. A large proportion of COPD patients suffer from cardiovascular comorbidities. Thromboembolic events contribute considerably to morbidity and mortality in these subjects. This review summarizes the current evidence regarding the association of COPD with increased thromboembolic risk. We discuss multiple mechanisms potentially linking these conditions and available pharmacological interventions reducing the risk of thrombotic arterial and venous events with special attention paid to new oral anticoagulants. PMID- 26559803 TI - Water Oxidation for Simplified Models of the Oxygen-Evolving Complex in Photosystem II. AB - For the main parts of the mechanism for water oxidation in photosystem II there has recently been very strong experimental support for the mechanism suggested by theoretical model studies. The question addressed in the present study is to what extent this knowledge can be used for the design of artificial catalysts. A major requirement for a useful artificial catalyst is that it is small enough to be synthesized. Small catalysts also have the big advantage that they could improve the catalysis per surface area. To make the mechanism found for PSII useful in this context, it needs to be analyzed in detail. A small model system was therefore used and the ligands were replaced one by one by water-derived ligands. Only the main chemical step of O-O bond formation was investigated in this initial study. The energetics for this small model and the larger one previously used for PSII are remarkably similar, which is the most important result of the present study. This shows that small model complexes have a potential for being very good water oxidation catalysts. It was furthermore found that there is a clear correlation between the barrier height for O-O bond formation and the type of optimal structure for the S3 state. The analysis shows that a flexible central part of the complex is the key for efficient water oxidation. PMID- 26559804 TI - Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function. AB - BACKGROUND: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. MATERIALS AND METHODS: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. RESULTS: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. CONCLUSION: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique. PMID- 26559805 TI - Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety? AB - INTRODUCTION: TNF-alpha inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-alpha inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. AREAS COVERED: infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents. EXPERT OPINION: IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab. PMID- 26559807 TI - Erratum. PMID- 26559806 TI - Incidence and duration of hepatitis E virus infection in Dutch blood donors. AB - BACKGROUND: The incidence of hepatitis E virus (HEV) infection in the Netherlands is high. Blood donors are not routinely screened for HEV infection, but since January 2013, donations used for the production of solvent/detergent (S/D) treated plasma have been screened for HEV RNA. STUDY DESIGN AND METHODS: Donations were screened for HEV RNA in pools of 96 and 192 donations. In addition, all donations made between 60 days before and after each HEV RNA positive donation were tested individually for HEV RNA and anti-HEV immunoglobulin G. RESULTS: The screening of 59,474 donations between January 2013 and December 2014 resulted in identification of 45 HEV RNA-positive donations (0.076%) from 41 donors. HEV RNA loads ranged from 80 to 2.3 * 10(6) IU/mL. The number of positive donations increased significantly over time (p = 0.03). Thirty three of 90 donations made up to 60 days before or after HEV RNA-positive donations were positive when tested individually, while they had not been detected in the pool screening. The mean duration of HEV viremia in the healthy blood donor is estimated to be 68 days. CONCLUSION: The incidence of HEV infection in the Netherlands is high and increased during the study period. In 2013 and 2014, HEV RNA was detected in 1 per 762 donations intended for production of S/D plasma. PMID- 26559808 TI - Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells. AB - Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure. PMID- 26559809 TI - Evaluation of the linkage-disequilibrium method for the estimation of effective population size when generations overlap: an empirical case. AB - BACKGROUND: Within the genetic methods for estimating effective population size (N e ), the method based on linkage disequilibrium (LD) has advantages over other methods, although its accuracy when applied to populations with overlapping generations is a matter of controversy. It is also unclear the best way to account for mutation and sample size when this method is implemented. Here we have addressed the applicability of this method using genome-wide information when generations overlap by profiting from having available a complete and accurate pedigree from an experimental population of Iberian pigs. Precise pedigree-based estimates of N e were considered as a baseline against which to compare LD-based estimates. METHODS: We assumed six different statistical models that varied in the adjustments made for mutation and sample size. The approach allowed us to determine the most suitable statistical model of adjustment when the LD method is used for species with overlapping generations. A novel approach used here was to treat different generations as replicates of the same population in order to assess the error of the LD-based N e estimates. RESULTS: LD-based N e estimates obtained by estimating the mutation parameter from the data and by correcting sample size using the 1/2n term were the closest to pedigree-based estimates. The N e at the time of the foundation of the herd (26 generations ago) was 20.8 +/- 3.7 (average and SD across replicates), while the pedigree-based estimate was 21. From that time on, this trend was in good agreement with that followed by pedigree-based N e. CONCLUSIONS: Our results showed that when using genome-wide information, the LD method is accurate and broadly applicable to small populations even when generations overlap. This supports the use of the method for estimating N e when pedigree information is unavailable in order to effectively monitor and manage populations and to early detect population declines. To our knowledge this is the first study using replicates of empirical data to evaluate the applicability of the LD method by comparing results with accurate pedigree-based estimates. PMID- 26559810 TI - Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options. AB - INTRODUCTION: A residual risk of morbidity and mortality from cardiovascular (CV) disease remains despite statin therapy. This situation has generated an interest in finding novel approaches of combining statins with other lipid-lowering agents, or finding new lipid and non-lipid targets, such as triglycerides, high density lipoprotein cholesterol (HDL-C), non-HDL-C, proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, cholesterol ester transfer protein (CETP), lipoprotein (a), fibrinogen or C-reactive protein. AREAS COVERED: The recent results from the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated an incremental clinical benefit when ezetimibe, a non-statin agent, was added to simvastatin therapy. EXPERT OPINION: The results from IMPROVE-IT revalidated the concept that low-density lipoprotein cholesterol (LDL-C) levels are a clinically relevant treatment goal. This trial also suggested that further decrease of LDL-C levels (53 vs. 70 mg/dl; 1.4 vs. 1.8 mmol/l) was more beneficial in lowering CV events. This "even lower is even better" evidence for LDL-C levels may influence future guidelines and the use of new drugs. Furthermore, these findings make ezetimibe a more realistic option to treat patients with statin intolerance or those who cannot achieve LDL-C targets with statin monotherapy. PMID- 26559811 TI - Genotoxicity Induced by Foetal and Infant Exposure to Magnetic Fields and Modulation of Ionising Radiation Effects. AB - BACKGROUND: Few studies have investigated the toxicity and genotoxicity of extremely low frequency magnetic fields (ELF-MF) during prenatal and neonatal development. These phases of life are characterized by cell proliferation and differentiation, which might make them sensitive to environmental stressors. Although in vitro evidences suggest that ELF-MF may modify the effects of ionizing radiation, no research has been conducted so far in vivo on the genotoxic effects of ELF-MF combined with X-rays. AIM AND METHODS: Aim of this study was to investigate in somatic and germ cells the effects of chronic ELF-MF exposure from mid gestation until weaning, and any possible modulation produced by ELF-MF exposure on ionizing radiation-induced damage. Mice were exposed to 50 Hz, 65 MUT magnetic field, 24 hours/day, for a total of 30 days, starting from 12 days post-conception. Another group was irradiated with 1 Gy X-rays immediately before ELF-MF exposure, other groups were only X-irradiated or sham-exposed. Micronucleus test on blood erythrocytes was performed at multiple times from 1 to 140 days after birth. Additionally, 42 days after birth, genotoxic and cytotoxic effects on male germ cells were assessed by comet assay and flow cytometric analysis. RESULTS: ELF-MF exposure had no teratogenic effect and did not affect survival, growth and development. The micronucleus test indicated that ELF-MF induced a slight genotoxic damage only after the maximum exposure time and that this effect faded away in the months following the end of exposure. ELF-MF had no effects on ionizing radiation (IR)-induced genotoxicity in erythrocytes. Differently, ELF-MF appeared to modulate the response of male germ cells to X rays with an impact on proliferation/differentiation processes. These results point to the importance of tissue specificity and development on the impact of ELF-MF on the early stages of life and indicate the need of further research on the molecular mechanisms underlying ELF-MF biological effects. PMID- 26559812 TI - Deficiency of IL-17A, but not the prototypical Th17 transcription factor RORgammat, decreases murine spontaneous intestinal tumorigenesis. AB - While inflammation has been associated with the development and progression of colorectal cancer, the exact role of the inflammatory Th17 pathway remains unclear. In this study, we aimed to determine the relative importance of IL-17A and the master regulator of the Th17 pathway, the transcription factor RORgammat, in the sporadic intestinal neoplasia of APC(MIN/+) mice and in human colorectal cancer. We show that levels of IL-17A are increased in human colon cancer as compared to adjacent uninvolved colon. Similarly, naive helper T cells from colorectal cancer patients are more inducible into the Th17 pathway. Furthermore, IL-17A, IL-21, IL-22, and IL-23 are all demonstrated to be directly mitogenic to human colorectal cancer cell lines. Nevertheless, deficiency of IL-17A but not RORgammat is associated with decreased spontaneous intestinal tumorigenesis in the APC(MIN/+) mouse model, despite the fact that helper T cells from RORgammat deficient APC(MIN/+) mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORgammat deficient APC(MIN/+) mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and RORgammat-deficient APC(MIN/+) mice may explain the difference in adenoma development. PMID- 26559813 TI - NK-92: an 'off-the-shelf therapeutic' for adoptive natural killer cell-based cancer immunotherapy. AB - Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however always remain variable due to individual differences of donors or patients. Long-term storage of clinical NK cell lots to allow repeated clinical applications remains an additional challenge. In contrast, the established and well-characterized cell line NK-92 can be easily and reproducibly expanded from a good manufacturing practice (GMP)-compliant cryopreserved master cell bank. Moreover, no cost-intensive cell purification methods are required. To date, NK-92 has been intensively studied. The cells displayed superior cytotoxicity against a number of tumor types tested, which was confirmed in preclinical mouse studies. Subsequent clinical testing demonstrated safety of NK-92 infusions even at high doses. Despite the phase I nature of the trials conducted so far, some efficacy was noted, particularly against lung tumors. Furthermore, to overcome tumor resistance and for specific targeting, NK 92 has been engineered to express a number of different chimeric antigen receptors (CARs), including targeting, for example, CD19 or CD20 (anti-B cell malignancies), CD38 (anti-myeloma) or human epidermal growth factor receptor 2 (HER2; ErbB2; anti-epithelial cancers). The concept of an NK cell line as an allogeneic cell therapeutic produced 'off-the-shelf' on demand holds great promise for the development of effective treatments. PMID- 26559814 TI - Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island. AB - BACKGROUND: Type 1 diabetes incidence presents a decreasing gradient in Europe from the Nordic countries to the Mediterranean ones. Exception to this gradient is represented by Sardinia, the second largest Mediterranean island whose population shows the highest incidence in Europe, after Finland. The genetic features of this population have created a fertile ground for the epidemic of the disease, however, as well as being strikingly high, the incidence rate has suddenly presented a continuous increase from the '50s, not explainable by accumulation of new genetic variants. Several environmental factors have been taken into account, possibly interacting with the genetic/epigenetic scenario, but there are no strong evidences to date. METHODS: The present study investigated the hypothesis that geochemical elements could create permissive environmental conditions for autoimmune diabetes. An ecological analysis was performed to test possible correlations between the values of eight elements in stream sediments and type 1 diabetes incidence rate in Sardinia. RESULTS: Analyses revealed negative associations between elements, such as Co, Cr, Cu, Mn, Ni, Zn, and type 1 diabetes incidence. CONCLUSIONS: The results suggest a possible protective role of some elements against the onset of the disease. PMID- 26559815 TI - Toll-Like Receptor 2 Targeted Rectification of Impaired CD8+ T Cell Functions in Experimental Leishmania donovani Infection Reinstates Host Protection. AB - Leishmania donovani, a protozoan parasite, causes the disease visceral leishmanisis (VL), characterized by inappropriate CD8+ T-cell activation. Therefore, we examined whether the Toll-like Receptor 2 (TLR2) ligand Ara-LAM, a cell wall glycolipid from non-pathogenic Mycobacterium smegmatis, would restore CD8+ T-cell function during VL. We observed that by efficient upregulation of TLR2 signaling-mediated NF-kappaB translocation and MAPK signaling in CD8+ T cells (CD25+CD28+IL-12R+IFN-gammaR+), Ara-LAM triggered signaling resulted in the activation of T-bet, which in turn, induced transcription favourable histone modification at the IFN-gamma, perforin, granzyme-B promoter regions in CD8+ T cells. Thus, we conclude that Ara-LAM induced efficient activation of effector CD8+ T-cells by upregulating the expression of IFN-gamma, perforin and granzyme-B in an NF-kappaB and MAPK induced T-bet dependent manner in VL. PMID- 26559816 TI - Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort. AB - BACKGROUND: There is limited evidence on the efficacy of post-exposure prophylaxis (PEP) for sexual exposures. We sought to determine the factors associated with adherence to treatment and describe the incidence of PEP failures in a Montreal clinic. METHODS: We prospectively assessed all patients consulting for PEP following sexual exposures from October 2000 to July 2014. Patients were followed at 4 and 16 weeks after starting PEP. Treatment adherence was determined by self-report at week 4. Multivariable logistic regression was used to estimate the factors predicting adherence to treatment. RESULTS: 3547 PEP consults were included. Patients were mainly male (92%), MSM (83%) and sought PEP for anal intercourse (72%). Seventy-eight percent (n = 2772) of patients received a prescription for PEP, consisting of Tenofovir/Emtracitabine (TVD) + Lopinavir/Ritonavir (LPV) in 74% of cases, followed by Zidovudine/Lamivudine (CBV) + LPV (10%) and TVD + Raltegravir (RAL) (8%). Seventy percent of patients were adherent to treatment. Compared to TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44-0.75), while no difference was observed for patients taking TVD+RAL (OR 1.15, 95% CI 0.83-1.59). First-time PEP consults, older and male patients were also more adherent to treatment. Ten treated patients seroconverted (0.37%) during the study period, yet only 1 case can be attributed to PEP failure (failure rate = 0.04%). CONCLUSION: PEP regimen was associated with treatment adherence. Patients were more likely to be adherent to TVD-based regimens. Ten patients seroconverted after taking PEP; however, only 1 case was a PEP failure as the remaining patients continued to engage in high-risk behavior during follow-up. One month PEP is an effective preventive measure to avoid HIV infection. PMID- 26559817 TI - Food Choices and Consequences for the Nutritional Status: Insights into Nutrition Transition in an Hospital Community. AB - INTRODUCTION: Although economic development is generally accompanied by improvements in the overall nutritional status of the country's population the 'nutritional transition' often involves a shift to high energy diets and less exercise with negative consequences. This pilot study was done to examine if education of parents operates at the household level to influence dietary choices and the nutritional status of children in a small community of hospital workers. MATERIAL AND METHODS: 3 groups of persons with varying skill and education levels participated. Weighed food logs were used in all households to calculate 'adult equivalent' per-capita-consumption. Nutrients were calculated using nutrients calculator software. BMI was used to classify children as underweight, normal weight and overweight. RESULTS: 128 individuals participated from 30 families included 47 children. 10 children (21%) were underweight, 29 (62%) were normal and 8 (17%) were overweight. Energy consumption was highest in families with overweight children 2692 +/-502 compared to 2259 +/-359 in families with normal weight and 2031+/-354 in the family of underweight children. These differences were statistically significant. 42% underweight children belonged to Class 1 at the lowest skill level and there were no overweight children in this group. Most of the overweight children belonged to Class 2. In Class 3 there were no underweight children and the majority was normal weight children. CONCLUSION: Underweight children came from the poorer households. Per capita intake of the family as a whole correlated well with BMI in the children. There was increased obesity in middle income families belonging to Class 2-probably in families who move up the scale from deprivation. Nutritional status in children correlated mostly with maternal education status. PMID- 26559819 TI - Role of the left frontal aslant tract in stuttering: a brain stimulation and tractographic study. AB - The neural correlates of stuttering are to date incompletely understood. Although the possible involvement of the basal ganglia, the cerebellum and certain parts of the cerebral cortex in this speech disorder has previously been reported, there are still not many studies investigating the role of white matter fibers in stuttering. Axonal stimulation during awake surgery provides a unique opportunity to study the functional role of structural connectivity. Here, our goal was to investigate the white matter tracts implicated in stuttering, by combining direct electrostimulation mapping and postoperative tractography imaging, with a special focus on the left frontal aslant tract. Eight patients with no preoperative stuttering underwent awake surgery for a left frontal low-grade glioma. Intraoperative cortical and axonal electrical mapping was used to interfere in speech processing and subsequently provoke stuttering. We further assessed the relationship between the subcortical sites leading to stuttering and the spatial course of the frontal aslant tract. All patients experienced intraoperative stuttering during axonal electrostimulation. On postsurgical tractographies, the subcortical distribution of stimulated sites matched the topographical position of the left frontal aslant tract. This white matter pathway was preserved during surgery, and no patients had postoperative stuttering. For the first time to our knowledge, by using direct axonal stimulation combined with postoperative tractography, we provide original data supporting a pivotal role of the left frontal aslant tract in stuttering. We propose that this speech disorder could be the result of a disconnection within a large-scale cortico-subcortical circuit subserving speech motor control. PMID- 26559818 TI - Trefoil Factor-3 (TFF3) Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2. AB - Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3) is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC). MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression. PMID- 26559820 TI - Mal de debarquement syndrome: a systematic review. AB - Mal de debarquement (MdD) is a subjective perception of self-motion after exposure to passive motion, in most cases sea travel, hence the name. Mal de debarquement occurs quite frequently in otherwise healthy individuals for a short period of time (several hours). However, in some people symptoms remain for a longer period of time or even persist and this is then called mal de debarquement syndrome (MdDS). The underlying pathogenesis is poorly understood and therefore, treatment options are limited. In general, limited studies have focused on the topic, but the past few years more and more interest has been attributed to MdDS and its facets, which is reflected by an increasing number of papers. Till date, some interesting reviews on the topic have been published, but a systematic review of the literature is lacking and could help to address the shortcomings and flaws of the current literature. We here present a systematic review of MdD(S) based on a systematic search of medical databases employing predefined criteria, using the terms "mal de debarquement" and "sea legs". Based on this, we suggest a list of criteria that could aid healthcare professionals in the diagnosis of MdDS. Further research needs to address the blank gaps by addressing how prevalent MdD(S) really is, by digging deeper into the underlying pathophysiology and setting up prospective, randomized placebo-controlled studies to evaluate the effectiveness of possible treatment strategies. PMID- 26559821 TI - The modified ultrasound pattern sum score mUPSS as additional diagnostic tool for genetically distinct hereditary neuropathies. AB - The objective of this study is to evaluate the nerve ultrasound characteristics in genetically distinct inherited neuropathies, the value of the modified ultrasound pattern sum score (mUPSS) to differentiate between the subtypes and the correlation of ultrasound with nerve conduction studies (NCS), disease duration and severity. All patients underwent a standardized neurological examination, ultrasound, and NCS. In addition, genetic testing was performed. Consequently, mUPSS was applied, which is a sum-score of cross-sectional areas (CSA) at predefined anatomical points in different nerves. 31 patients were included (10xCharcot-Marie-Tooth (CMT)1a, 3xCMT1b, 3xCMTX, 9xCMT2, 6xHNPP [Hereditary neuropathy with liability to pressure palsies]). Generalized, homogeneous nerve enlargement and significantly increased UPS scores emphasized the diagnosis of demyelinating neuropathy, particularly CMT1a and CMT1b. The amount of enlargement did not depend on disease duration, symptom severity, height and weight. In CMTX the nerves were enlarged, as well, however, only in the roots and lower limbs, most prominent in men. In CMT2 no significant enlargement was detectable. In HNPP the CSA values were increased at entrapped sites, and not elsewhere. However, a distinction from CMT1, which also showed enlarged CSA values at entrapment sites, was only possible by calculating the entrapment ratios and entrapment score. The mUPSS allowed distinction between CMT1a (increased UPS scores, entrapment ratios <1.0) and HNPP (low UPS scores, entrapment ratios >1.4), while CMT1b and CMTX showed intermediate UPS types and entrapment ratios <1.0. Although based on few cases, ultrasound revealed consistent and homogeneous nerve alteration in certain inherited neuropathies. The modified UPSS is a quantitative tool, which may provide useful information for diagnosis, differentiation and follow-up evaluation in addition to NCS and molecular testing. PMID- 26559823 TI - Thoracic and cardiovascular surgery in Japan during 2013: Annual report by The Japanese Association for Thoracic Surgery. PMID- 26559824 TI - Botulinum toxin drugs: brief history and outlook. AB - The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox((r)) and Dysport((r)) dominated the international BT market. Later, Myobloc((r))/NeuroBloc((r)), a liquid BT type B drug, came out, but failed. Xeomin((r)) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur. PMID- 26559822 TI - Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy--Effects of Therapeutic Alginate Implant in Rat Models. AB - Spinal cord injury (SCI) induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier transform infrared (FT-IR) spectroscopy was applied to assess the outcomes of implants made of a novel type of non-functionalized soft calcium alginate hydrogel in a rat model of spinal cord hemisection (n = 28). Using FT-IR spectroscopic imaging, we evaluated the stability of the implants and the effects on morphology and biochemistry of the injured tissue one and six months after injury. A semi-quantitative evaluation of the distribution of lipids and collagen showed that alginate significantly reduced injury-induced demyelination of the contralateral white matter and fibrotic scarring in the chronic state after SCI. The spectral information enabled to detect and localize the alginate hydrogel at the lesion site and proved its long-term persistence in vivo. These findings demonstrate a positive impact of alginate hydrogel on recovery after SCI and prove FT-IR spectroscopic imaging as alternative method to evaluate and optimize future SCI repair strategies. PMID- 26559825 TI - CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches. AB - The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only. A case-control association study was performed for HFA (HFA, n = 105; controls, n = 133). Moreover, we performed a family-based association study (DFAM) analysis (HFA, n = 44; siblings, n = 57). Individuals were genotyped for the two most frequently reported single nucleotide polymorphisms (SNPs) in the CNTNAP2 gene (rs2710102, rs7794745). Furthermore, a meta-analysis using the MIX2 software integrated our results with previously published data. A significant association for the carriers of the T-allele of the rs7794745 with HFA was found in the case-control sample [OR = 1.547; (95 % CI 1.056-2.266); p = 0.025]. No association could be found by DFAM with any of the CNTNAP2 SNPs with HFA. The meta-analysis of both SNPs did not show a significant association with either ASD or with HFA. Overall, including case-control, sibs, and meta-analysis, we could not detect any significant association with the CNTNAP2 gene and HFA. Our results point in the direction that CNTNAP2 may not play a major role in HFA, but rather seems to have a significance in neurodevelopmental disorders or in individuals displaying intellectual delays. PMID- 26559826 TI - Next-Generation mRNA Sequencing Reveals Pyroptosis-Induced CD4+ T Cell Death in Early Simian Immunodeficiency Virus-Infected Lymphoid Tissues. AB - Lymphoid tissues (LTs) are the principal sites where human immunodeficiency virus type 1 (HIV-1) replicates and virus-host interactions take place, resulting in immunopathology in the form of inflammation, immune activation, and CD4(+) T cell death. The HIV-1 pathogenesis in LTs has been extensively studied; however, our understanding of the virus-host interactions in the very early stages of infection remains incomplete. We investigated virus-host interactions in the rectal draining lymph nodes (dLNs) of rhesus macaques at different times after intrarectal inoculation (days postinoculation [dpi]) with simian immunodeficiency virus (SIV). At 3 dpi, 103 differentially expressed genes (DEGs) were detected using next-generation mRNA sequencing (RNA-seq). At 6 and 10 dpi, concomitant with increased SIV replication, 366 and 1,350 DEGs were detected, respectively, including upregulation of genes encoding proteins that play a role in innate antiviral immune responses, inflammation, and immune activation. Notably, genes (IFI16, caspase-1, and interleukin 1beta [IL-1beta]) in the canonical pyroptosis pathway were significantly upregulated in expression. We further validated increased pyroptosis using flow cytometry and found that the number of CD4(+) T cells expressing activated caspase-1 protein, the hallmark of ongoing pyroptosis, were significantly increased, which is correlated with decreased CD4(+) T cells in dLNs. Our results demonstrated that pyroptosis contributes to the CD4(+) T cell death in vivo in early SIV infection, which suggests that pyroptosis may play a pivotal role in the pathogenesis of SIV, and by extension, that of HIV-1, since pyroptosis not only induces CD4(+) T cell death but also amplifies inflammation and immune activation. Thus, blocking CD4(+) T cell pyroptosis could be a complementary treatment to antiretroviral therapy. IMPORTANCE: Although secondary lymphoid tissues (LTs) are principal sites of human immunodeficiency virus type 1 (HIV-1) replication, inflammation, immune activation, and CD4(+) T cell death, immunopathogenesis in LTs during early infection remains largely unknown. Using the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV rectal infection, we investigated early virus-host interactions. Our results revealed elevated potent host responses in early infection in LTs, including upregulation of genes involved in antiviral immune response, inflammation, and immune activation. Importantly, genes involved in the canonical pyroptosis pathway were significantly upregulated, and there was a strong correlation between CD4(+) T cell decrease and increased number of CD4(+) T cells expressing activated caspase-1 protein, demonstrating that pyroptosis contributes to CD4(+) T cell death in vivo in very early SIV infection. Our finding suggests that blocking pyroptosis may be able to decrease CD4(+) T cell loss during early SIV infection. PMID- 26559827 TI - Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation. AB - Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE: Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusive target for the serological diagnoses. This work reveals the structure of hantavirus NP, furthering the knowledge of hantavirus RNP formation, revealing the relationship between hantavirus NP and serological specificity and raising the potential for the development of new diagnosis and therapeutics targeting hantavirus infection. PMID- 26559829 TI - Viral Regulation of Cell Tropism in Human Cytomegalovirus. AB - The viral glycoproteins that decorate enveloped viruses play crucial roles in cell entry and in large part dictate the spectrum of cell types that a virus can infect. The identification in human cytomegalovirus (HCMV) of a viral endoplasmic reticulum (ER)-resident glycoprotein that regulates the composition of alternative viral envelope glycoprotein complexes raises the intriguing possibility that certain viruses might actively regulate the tropism of progeny virions to improve their fitness or to navigate through the host. PMID- 26559828 TI - Zoonotic Potential of Simian Arteriviruses. AB - Wild nonhuman primates are immediate sources and long-term reservoirs of human pathogens. However, ethical and technical challenges have hampered the identification of novel blood-borne pathogens in these animals. We recently examined RNA viruses in plasma from wild African monkeys and discovered several novel, highly divergent viruses belonging to the family Arteriviridae. Close relatives of these viruses, including simian hemorrhagic fever virus, have caused sporadic outbreaks of viral hemorrhagic fever in captive macaque monkeys since the 1960s. However, arterivirus infection in wild nonhuman primates had not been described prior to 2011. The arteriviruses recently identified in wild monkeys have high sequence and host species diversity, maintain high viremia, and are prevalent in affected populations. Taken together, these features suggest that the simian arteriviruses may be "preemergent" zoonotic pathogens. If not, this would imply that biological characteristics of RNA viruses thought to facilitate zoonotic transmission may not, by themselves, be sufficient for such transmission to occur. PMID- 26559830 TI - Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors. AB - Protease is essential for retroviral replication, and protease inhibitors (PI) are important for treating HIV infection. HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 PI, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. The mechanisms for this resistance are unclear; although HIV-1 and HIV-2 proteases share just 38 to 49% sequence identity, all critical structural features of proteases are conserved. Structural studies have implicated four amino acids in the ligand-binding pocket (positions 32, 47, 76, and 82). We constructed HIV-2ROD9 molecular clones encoding the corresponding wild-type HIV-1 amino acids (I32V, V47I, M76L, and I82V) either individually or together (clone PRDelta4) and compared the phenotypic sensitivities (50% effective concentration [EC50]) of mutant and wild-type viruses to nine FDA-approved PI. Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRDelta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI. We also compared crystallographic structures of wild-type HIV-1 and HIV-2 proteases complexed with amprenavir and darunavir to models of the PRDelta4 enzyme. These models suggest that the amprenavir sensitivity of PRDelta4 is attributable to stabilizing enzyme-inhibitor interactions in the P2 and P2' pockets of the protease dimer. Together, our results show that the combination of four amino acid changes in HIV-2 protease confer a pattern of PI susceptibility comparable to that of HIV-1, providing a structural rationale for intrinsic HIV-2 PI resistance and resolving long-standing questions regarding the determinants of differential PI susceptibility in HIV-1 and HIV-2. IMPORTANCE: Proteases are essential for retroviral replication, and HIV-1 and HIV-2 proteases share a great deal of structural similarity. However, only three of nine FDA-approved HIV-1 protease inhibitors (PI) are active against HIV-2. The underlying reasons for intrinsic PI resistance in HIV-2 are not known. We examined the contributions of four amino acids in the ligand-binding pocket of the enzyme that differ between HIV-1 and HIV-2 by constructing HIV-2 clones encoding the corresponding HIV-1 amino acids and testing the PI susceptibilities of the resulting viruses. We found that the HIV-2 clone containing all four changes (PRDelta4) was as susceptible as HIV-1 to all nine PI. We also modeled the PRDelta4 enzyme structure and compared it to existing crystallographic structures of HIV-1 and HIV-2 proteases complexed with amprenavir and darunavir. Our findings demonstrate that four positions in the ligand-binding cleft of protease are the primary cause of HIV-2 PI resistance. PMID- 26559831 TI - The Cellular Protein Complex Associated with a Transforming Region of E1A Contains c-MYC. AB - The cell-transforming activity of human adenovirus 5 (hAd5) E1A is mediated by the N-terminal half of E1A, which interacts with three different major cellular protein complexes, p300/CBP, TRRAP/p400, and pRb family members. Among these protein interactions, the interaction of pRb family proteins with conserved region 2 (CR2) of E1A is known to promote cell proliferation by deregulating the activities of E2F family transcription factors. The functional consequences of interaction with the other two protein complexes in regulating the transforming activity of E1A are not well defined. Here, we report that the E1A N-terminal region also interacted with the cellular proto-oncoprotein c-MYC and the homolog of enhancer of yellow 2 (ENY2). Our results suggested that these proteins interacted with an essential E1A transforming domain spanning amino acid residues 26 to 35 which also interacted with TRRAP and p400. Small interfering RNA (siRNA) mediated depletion of TRRAP reduced c-MYC interaction with E1A, while p400 depletion did not. In contrast, depletion of TRRAP enhanced ENY2 interaction with E1A, suggesting that ENY2 and TRRAP may interact with E1A in a competitive manner. The same E1A region additionally interacted with the constituents of a deubiquitinase complex consisting of USP22, ATXN7, and ATXN7L3 via TRRAP. Acute short hairpin RNA (shRNA)-mediated depletion of c-MYC reduced the E1A transforming activity, while depletion of ENY2 and MAX did not. These results suggested that the association of c-MYC with E1A may, at least partially, play a role in the E1A transformation activity, independently of MAX. IMPORTANCE: The transforming region of adenovirus E1A consists of three short modules which complex with different cellular protein complexes. The mechanism by which one of the transforming modules, CR2, promotes cell proliferation, through inactivating the activities of the pRb family proteins, is better understood than the activities of the other domains. Our analysis of the E1A proteome revealed the presence of the proto-oncoprotein c-MYC and of ENY2. We mapped these interactions to a critical transforming module of E1A that was previously known to interact with the scaffolding molecule TRRAP and the E1A-binding protein p400. We showed that c-MYC interacted with E1A through TRRAP, while ENY2 interacted with it independently. The data reported here indicated that depletion of c-MYC in normal human cells reduced the transforming activity of E1A. Our result raises a novel paradigm in oncogenic transformation by a DNA viral oncogene, the E1A gene, that may exploit the activity of a cellular oncogene, the c-MYC gene, in addition to inactivation of the tumor suppressors, such as pRb. PMID- 26559832 TI - Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1. AB - Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE: This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species specific modulation of programmed necrosis by HSV. PMID- 26559833 TI - Minor Contribution of Chimeric Host-HIV Readthrough Transcripts to the Level of HIV Cell-Associated gag RNA. AB - Cell-associated HIV unspliced RNA is an important marker of the viral reservoir. HIV gag RNA-specific assays are frequently used to monitor reservoir activation. Because HIV preferentially integrates into actively transcribed genes, some of the transcripts detected by these assays may not represent genuine HIV RNA but rather chimeric host-HIV readthrough transcripts. Here, we demonstrate that in HIV-infected patients on suppressive combination antiretroviral therapy, such host-derived transcripts do not significantly contribute to the HIV gag RNA level. PMID- 26559834 TI - Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies. AB - Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE: The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses directed at the HA stalk region. Moreover, ferrets possessing HA stalk-specific antibody were protected against novel H1N1 virus infection and did not transmit the virus to naive contacts. PMID- 26559835 TI - HIV-1 Virion Production from Single Inducible Proviruses following T-Cell Activation Ex Vivo. AB - Quantifying induced virion production from single proviruses is important for assessing the effects of HIV-1 latency reversal agents. Limiting dilution ex vivo cultures of resting CD4(+) T cells from 14 HIV-positive volunteers revealed that virion production after T-cell activation from individual proviruses varies by 10,000-fold to 100,000-fold. High-producing proviruses were associated with increases in cell-associated HIV-1 DNA levels, suggesting that reactivated proviruses proliferate. Single-cell analyses are needed to investigate differences in proviral expansion and virus production following latency reversal. PMID- 26559836 TI - The C Terminus of the Core beta-Ladder Domain in Japanese Encephalitis Virus Nonstructural Protein 1 Is Flexible for Accommodation of Heterologous Epitope Fusion. AB - NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication. This mapped flexible region is located in the conserved tip of the core beta-ladder domain of the multimeric NS1 structure and is also known to contain certain linear epitopes, readily triggering specific antibody responses from the host. Despite becoming attenuated, recombinant JEV with insertion of a neutralizing epitope derived from enterovirus 71 (EV71) into the C-terminal end of NS1 not only could be normally released from infected cells, but also induced dual protective immunity for the host to counteract lethal challenge with either JEV or EV71 in neonatal mice. These results indicated that the secreted multimeric NS1 of flaviviruses may serve as a natural protein carrier to render epitopes of interest more immunogenic in the C terminus of the core beta-ladder domain. IMPORTANCE: The positive-sense RNA genomes of mosquito-borne flaviviruses appear to be flexible in terms of accommodating extra insertions of short heterologous antigens into their virus genes. Here, we illustrate that the newly identified C terminus of the core beta-ladder domain in NS1 could be readily inserted into entities such as EV71 epitopes, and the resulting NS1-epitope fusion proteins appeared to maintain normal virus replication, secretion ability, and multimeric formation from infected cells. Nonetheless, such an insertion attenuated the recombinant JEV in mice, despite having retained the brain replication ability observed in wild-type JEV. Mother dams immunized with recombinant JEV expressing EV71 epitope-NS1 fused proteins elicited neutralizing antibodies that protected the newborn mice against lethal EV71 challenge. Together, our results implied a potential application of JEV NS1 as a viral carrier protein to express a heterologous epitope to stimulate dual/multiple protective immunity concurrently against several pathogens. PMID- 26559837 TI - Human Cytomegalovirus Modulates Expression of Noncanonical Wnt Receptor ROR2 To Alter Trophoblast Migration. AB - Maternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV-infected fetus but also from indirect effects through placental infection and dysfunction. CMV alters Wingless (Wnt) signaling, an essential cellular pathway involved in placentation, as evidenced by reduced transcription of canonical Wnt target genes and decreased Wnt3a induced trophoblast migration. Whether CMV affects the noncanonical Wnt signaling pathway has been unclear. This study demonstrates for the first time that CMV infection inhibits Wnt5a-stimulated migration of human SGHPL-4 trophoblasts and that inhibition of the pathway restores normal migration of CMV-infected cells. Western blot and real-time PCR analyses show increased expression of noncanonical Wnt receptor ROR2 in CMV-infected trophoblasts. Mimicking the CMV-induced ROR2 protein expression via ectopic expression inhibited Wnt5a-induced trophoblast migration and reduced T cell-specific factor (TCF)/lymphoid enhancer-binding factor (LEF)-mediated transcription as measured using luciferase reporter assays. Gene silencing using small interfering RNA (siRNA) duplexes decreased ROR2 transcript and protein levels. In contrast, proliferation of SGHPL-4 trophoblasts, measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was not affected. The siRNA-mediated downregulation of ROR2 in trophoblasts rescued CMV-induced reduction in trophoblast migration. These data suggest a mechanism where CMV alters the expression of the Wnt receptor ROR2 to alter Wnt5a-mediated signaling and inhibit trophoblast motility. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in congenital CMV infections. IMPORTANCE: Maternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV infected fetus but also from indirect effects through placental infection and placental dysfunction. No effective therapy is currently proven to prevent or treat congenital CMV infection. Understanding the molecular underpinnings of CMV infection of the placenta is essential for therapeutic innovations and vaccine design. CMV alters canonical Wingless (Wnt) signaling, an essential cellular pathway involved in placental development. This study suggests a mechanism in which CMV alters the expression of noncanonical Wnt receptor ROR2 to alter motility of placental cells, which has important implications in the pathogenesis of CMV-induced placental dysfunction. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in congenital CMV infection. PMID- 26559838 TI - A Cell-Free Assembly System for Generating Infectious Human Papillomavirus 16 Capsids Implicates a Size Discrimination Mechanism for Preferential Viral Genome Packaging. AB - We have established a cell-free in vitro system to study human papillomavirus type 16 (HPV16) assembly, a poorly understood process. L1/L2 capsomers, obtained from the disassembly of virus-like particles (VLPs), were incubated with nuclear extracts to provide access to the range of cellular proteins that would be available during assembly within the host cell. Incorporation of a reporter plasmid "pseudogenome" was dependent on the presence of both nuclear extract and ATP. Unexpectedly, L1/L2 VLPs that were not disassembled prior to incubation with a reassembly mixture containing nuclear extract also encapsidated a reporter plasmid. As with HPV pseudoviruses (PsV) generated intracellularly, infection by cell-free particles assembled in vitro required the presence of L2 and was susceptible to the same biochemical inhibitors, implying the cell-free assembled particles use the infectious pathway previously described for HPV16 produced in cell culture. Using biochemical and electron microscopy analyses, we observed that, in the presence of nuclear extract, intact VLPs partially disassemble, providing a mechanistic explanation to how the exogenous plasmid was packaged by these particles. Further, we provide evidence that capsids containing an <8-kb pseudogenome are resistant to the disassembly/reassembly reaction. Our results suggest a novel size discrimination mechanism for papillomavirus genome packaging in which particles undergo iterative rounds of disassembly/reassembly, seemingly sampling DNA until a suitably sized DNA is encountered, resulting in the formation of a stable virion structure. IMPORTANCE: Little is known about papillomavirus assembly biology due to the difficulties in propagating virus in vitro. The cell-free assembly method established in this paper reveals a new mechanism for viral genome packaging and will provide a tractable system for further dissecting papillomavirus assembly. The knowledge gained will increase our understanding of virus-host interactions, help to identify new targets for antiviral therapy, and allow for the development of new gene delivery systems based on in vitro-generated papillomavirus vectors. PMID- 26559839 TI - Epstein-Barr Virus gp350 Can Functionally Replace the Rhesus Lymphocryptovirus Major Membrane Glycoprotein and Does Not Restrict Infection of Rhesus Macaques. AB - Primary Epstein-Barr virus (EBV) infection is the most common cause of infectious mononucleosis, and persistent infection is associated with multiple cancers. EBV vaccine development has focused on the major membrane glycoprotein, gp350, since it is the major target for antibodies that neutralize infection of B cells. However, EBV has tropism for both B cells and epithelial cells, and it is unknown whether serum neutralizing antibodies against B cell infection will provide sufficient protection against virus infection initiated at the oral mucosa. This could be stringently tested by passive antibody transfer and oral virus challenge in the rhesus macaque model for EBV infection. However, only neutralizing monoclonal antibodies (MAbs) against EBV are available, and EBV is unable to infect rhesus macaques because of a host range restriction with an unknown mechanism. We cloned the prototypic EBV-neutralizing antibody, 72A1, and found that recombinant 72A1 did not neutralize rhesus lymphocryptovirus (rhLCV) infection of macaque B cells. Therefore, we constructed a chimeric rhLCV in which the native major membrane glycoprotein was replaced with EBV gp350. This chimeric rhLCV became sensitive to neutralization by the 72A1 MAb, efficiently immortalized macaque B cells in vitro, and successfully established acute and persistent infection after oral inoculation of rhesus macaques. Thus, EBV gp350 can functionally replace rhLCV gp350 and does not restrict rhLCV infection in vitro or in vivo. The chimeric rhLCV enables direct use of an EBV-specific MAb to investigate the effects of serum neutralizing antibodies against B cell infection on oral viral challenge in rhesus macaques. IMPORTANCE: This study asked whether the EBV major membrane glycoprotein could functionally replace the rhLCV major membrane glycoprotein. We found that an rhLCV humanized with EBV gp350 is capable of efficiently immortalizing monkey B cells in vitro and reproduces acute and persistent infection after oral inoculation of macaques. These results advance our understanding of why EBV cannot infect rhesus macaques by proving that viral attachment through gp350 is not the mechanism for EBV host range restriction. Humanization of rhLCV with EBV gp350 also confers susceptibility to a potent EBV neutralizing MAb and provides a novel and significant enhancement to the rhesus macaque animal model where both the clinical utility and biological role of neutralizing MAbs against B cell or epithelial cell infection can now be directly tested in the most accurate animal model for EBV infection. PMID- 26559840 TI - Characterization of Recombinant Human Cytomegaloviruses Encoding IE1 Mutants L174P and 1-382 Reveals that Viral Targeting of PML Bodies Perturbs both Intrinsic and Innate Immune Responses. AB - PML is the organizer of cellular structures termed nuclear domain 10 (ND10) or PML-nuclear bodies (PML-NBs) that act as key mediators of intrinsic immunity against human cytomegalovirus (HCMV) and other viruses. The antiviral function of ND10 is antagonized by viral regulatory proteins such as the immediate early protein IE1 of HCMV. IE1 interacts with PML through its globular core domain (IE1CORE) and induces ND10 disruption in order to initiate lytic HCMV infection. Here, we investigate the consequences of a point mutation (L174P) in IE1CORE, which was shown to abrogate the interaction with PML, for lytic HCMV infection. We found that a recombinant HCMV encoding IE1-L174P displays a severe growth defect similar to that of an IE1 deletion virus. Bioinformatic modeling based on the crystal structure of IE1CORE suggested that insertion of proline into the highly alpha-helical domain severely affects its structural integrity. Consistently, L174P mutation abrogates the functionality of IE1CORE and results in degradation of the IE1 protein during infection. In addition, our data provide evidence that IE1CORE as expressed by a recombinant HCMV encoding IE1 1-382 not only is required to antagonize PML-mediated intrinsic immunity but also affects a recently described function of PML in innate immune signaling. We demonstrate a coregulatory role of PML in type I and type II interferon-induced gene expression and provide evidence that upregulation of interferon-induced genes is inhibited by IE1CORE. In conclusion, our data suggest that targeting PML by viral regulatory proteins represents a strategy to antagonize both intrinsic and innate immune mechanisms. IMPORTANCE: PML nuclear bodies (PML-NBs), which represent nuclear multiprotein complexes consisting of PML and additional proteins, represent important cellular structures that mediate intrinsic resistance against many viruses, including human cytomegalovirus (HCMV). During HCMV infection, the major immediate early protein IE1 binds to PML via a central globular domain (IE1CORE), and we have shown previously that this is sufficient to antagonize intrinsic immunity. Here, we demonstrate that modification of PML by IE1CORE not only abrogates intrinsic defense mechanisms but also attenuates the interferon response during infection. Our data show that PML plays a novel coregulatory role in type I as well as type II interferon-induced gene expression, which is antagonized by IE1CORE. Importantly, our finding supports the view that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to inhibit both intrinsic and innate immune defense mechanisms. PMID- 26559841 TI - Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic. AB - Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2 fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ~2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era. IMPORTANCE: HLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many-though not all HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era. PMID- 26559842 TI - Identification and Characterization of the Physiological Gene Targets of the Essential Lytic Replicative Epstein-Barr Virus SM Protein. AB - Epstein-Barr virus (EBV) SM protein is an essential lytic cycle protein with multiple posttranscriptional mechanisms of action. SM binds RNA and increases accumulation of specific EBV transcripts. Previous studies using microarrays and PCR have shown that SM-null mutants fail to accumulate several lytic cycle mRNAs and proteins at wild-type levels. However, the complete effect of SM on the EBV transcriptome has been incompletely characterized. Here we precisely identify the effects of SM on all EBV transcripts by high-throughput RNA sequencing, quantitative PCR (qPCR), and Northern blotting. The effect of SM on EBV mRNAs was highly skewed and was most evident on 13 late genes, demonstrating why SM is essential for infectious EBV production. EBV DNA replication was also partially impaired in SM mutants, suggesting additional roles for SM in EBV DNA replication. While it has been suggested that SM specificity is based on recognition of either RNA sequence motifs or other sequence properties, no such unifying property of SM-responsive targets was discernible. The binding affinity of mRNAs for SM also did not correlate with SM responsiveness. These data suggest that while target RNA binding by SM may be required for its effect, specific activation by SM is due to differences in inherent properties of individual transcripts. We therefore propose a new model for the mechanism of action and specificity of SM and its homologs in other herpesviruses: that they bind many RNAs but only enhance accumulation of those that are intrinsically unstable and poorly expressed. IMPORTANCE: This study examines the mechanism of action of EBV SM protein, which is essential for EBV replication and infectious virus production. Since SM protein is not similar to any cellular protein and has homologs in all other human herpesviruses, it has potential importance as a therapeutic target. Here we establish which EBV RNAs are most highly upregulated by SM, allowing us to understand why it is essential for EBV replication. By comparing and characterizing these RNA transcripts, we conclude that the mechanism of specific activity is unlikely to be based simply on preferential recognition of a target motif. Rather, SM binding to its target RNA may be necessary but not sufficient for enhancing accumulation of the RNA. Preferential effects of SM on its most responsive RNA targets may depend on other inherent characteristics of these specific mRNAs that require SM for efficient expression, such as RNA stability. PMID- 26559843 TI - A Comprehensive RNA Sequencing Analysis of the Adeno-Associated Virus (AAV) Type 2 Transcriptome Reveals Novel AAV Transcripts, Splice Variants, and Derived Proteins. AB - Adeno-associated virus (AAV) is recognized for its bipartite life cycle with productive replication dependent on coinfection with adenovirus (Ad) and AAV latency being established in the absence of a helper virus. The shift from latent to Ad-dependent AAV replication is mostly regulated at the transcriptional level. The current AAV transcription map displays highly expressed transcripts as found upon coinfection with Ad. So far, AAV transcripts have only been characterized on the plus strand of the AAV single-stranded DNA genome. The AAV minus strand is assumed not to be transcribed. Here, we apply Illumina-based RNA sequencing (RNA Seq) to characterize the entire AAV2 transcriptome in the absence or presence of Ad. We find known and identify novel AAV transcripts, including additional splice variants, the most abundant of which leads to expression of a novel 18-kDa Rep/VP fusion protein. Furthermore, we identify for the first time transcription on the AAV minus strand with clustered reads upstream of the p5 promoter, confirmed by 5' rapid amplification of cDNA ends and RNase protection assays. The p5 promoter displays considerable activity in both directions, a finding indicative of divergent transcription. Upon infection with AAV alone, low-level transcription of both AAV strands is detectable and is strongly stimulated upon coinfection with Ad. IMPORTANCE: Next-generation sequencing (NGS) allows unbiased genome-wide analyses of transcription profiles, used here for an in depth analysis of the AAV2 transcriptome during latency and productive infection. RNA-Seq analysis led to the discovery of novel AAV transcripts and splice variants, including a derived, novel 18-kDa Rep/VP fusion protein. Unexpectedly, transcription from the AAV minus strand was discovered, indicative of divergent transcription from the p5 promoter. This finding opens the door for novel concepts of the switch between AAV latency and productive replication. In the absence of a suitable animal model to study AAV in vivo, combined in cellulae and in silico studies will help to forward the understanding of the unique, bipartite AAV life cycle. PMID- 26559844 TI - Occupancy of RNA Polymerase II Phosphorylated on Serine 5 (RNAP S5P) and RNAP S2P on Varicella-Zoster Virus Genes 9, 51, and 66 Is Independent of Transcript Abundance and Polymerase Location within the Gene. AB - Regulation of gene transcription in varicella-zoster virus (VZV), a ubiquitous human neurotropic alphaherpesvirus, requires coordinated binding of multiple host and virus proteins onto specific regions of the virus genome. Chromatin immunoprecipitation (ChIP) is widely used to determine the location of specific proteins along a genomic region. Since the size range of sheared virus DNA fragments governs the limit of accurate protein localization, particularly for compact herpesvirus genomes, we used a quantitative PCR (qPCR)-based assay to determine the efficiency of VZV DNA shearing before ChIP, after which the assay was used to determine the relationship between transcript abundance and the occupancy of phosphorylated RNA polymerase II (RNAP) on the gene promoter, body, and terminus of VZV genes 9, 51, and 66. The abundance of VZV gene 9, 51, and 66 transcripts in VZV-infected human fetal lung fibroblasts was determined by reverse transcription-linked quantitative PCR. Our results showed that the C terminal domain of RNAP is hyperphosphorylated at serine 5 (S5(P)) on VZV genes 9, 51, and 66 independently of transcript abundance and the location within the virus gene at both 1 and 3 days postinfection (dpi). In contrast, phosphorylated serine 2 (S2(P))-modified RNAP was not detected at any virus gene location at 3 dpi and was detected at levels only slightly above background levels at 1 dpi. IMPORTANCE: Regulation of herpesvirus gene transcription is an elaborate choreography between proteins and DNA that is revealed by chromatin immunoprecipitation (ChIP). We used a quantitative PCR-based assay to determine fragment size after DNA shearing, a critical parameter in ChIP assays, and exposed a basic difference in the mechanism of transcription between mammalian cells and VZV. We found that hyperphosphorylation at serine 5 of the C-terminal domain of RNAP along the lengths of VZV genes (the promoter, body, and transcription termination site) was independent of mRNA abundance. In contrast, little to no enrichment of serine 3 phosphorylation of RNAP was detected at these virus gene regions. This is distinct from the findings for RNAP at highly regulated host genes, where RNAP S5(P) occupancy decreased and S2(P) levels increased as the polymerase transited through the gene. Overall, these results suggest that RNAP associates with human and virus transcriptional units through different mechanisms. PMID- 26559845 TI - Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase. AB - Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-kappaB promoter activity in AP-1- and NF-kappaB-luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-kappaB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production. IMPORTANCE: Epstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency. PMID- 26559847 TI - Human Herpesvirus 6A U14 Is Important for Virus Maturation. AB - Human herpesvirus 6A (HHV-6A) U14 is a virion protein with little known function in virus propagation. Here, we elucidated its function by constructing and analyzing U14-mutated viruses. We found that U14 is essential for HHV-6A propagation. We then constructed a mutant virus harboring dysfunctional U14. This virus showed severely reduced growth and retarded maturation. Taken together, these data indicate that U14 plays an important role during HHV-6A maturation. PMID- 26559846 TI - A Herpes Simplex Virus 2 (HSV-2) gD Mutant Impaired for Neural Tropism Is Superior to an HSV-2 gD Subunit Vaccine To Protect Animals from Challenge with HSV-2. AB - A recent phase 3 trial with soluble herpes simplex virus 2 (HSV-2) glycoprotein D (gD2t) in adjuvant failed to show protection against genital herpes. We postulated that live attenuated HSV-2 would provide more HSV antigens for induction of virus-specific antibodies and cellular immunity than would gD2t. We previously reported an HSV-2 mutant, HSV2-gD27, in which the nectin-1 binding domain of gD2 is altered so that the virus is impaired for infecting neural cells, but not epithelial cells, in vitro and is impaired for infecting dorsal root ganglia in mice (K. Wang, J. D. Kappel, C. Canders, W. F. Davila, D. Sayre, M. Chavez, L. Pesnicak, and J. I. Cohen, J Virol 86:12891-12902, 2012, doi:10.1128/JVI.01055-12). Here we report that the mutations in HSV2-gD27 were stable when the virus was passaged in cell culture and during acute infection of mice. HSV2-gD27 was attenuated in mice when it was inoculated onto the cornea, intramuscularly (i.m.), intravaginally, and intracranially. Vaccination of mice i.m. with HSV2-gD27 provided better inhibition of challenge virus replication in the vagina than when the virus was used to vaccinate mice intranasally or subcutaneously. Comparison of i.m. vaccinations with HSV2-gD27 versus gD2t in adjuvant showed that HSV2-gD27 induced larger reductions of challenge virus replication in the vagina and reduced latent viral loads in dorsal root ganglia but induced lower serum neutralizing antibody titers than those obtained with gD2t in adjuvant. Taken together, our data indicate that a live attenuated HSV-2 vaccine impaired for infection of neurons provides better protection from vaginal challenge with HSV-2 than that obtained with a subunit vaccine, despite inducing lower titers of HSV-2 neutralizing antibodies in the serum. IMPORTANCE: Genital herpes simplex is one of the most prevalent sexually transmitted diseases. Though HSV-2 disease is usually mild, it can be life threatening in neonates and immunocompromised persons. In addition, genital herpes increases the frequency of HIV infection and transmission. HSV-2 maintains a latent infection in sensory neurons and cannot be cleared with antiviral drugs. The virus frequently reactivates, resulting in virus shedding in the genital area, which serves as a source for transmission. A prophylactic vaccine is needed to prevent disease and to control the spread of the virus. Previous human trials of subunit vaccines have been unsuccessful. Here we report the results of vaccinating mice with a new type of live attenuated HSV-2 vaccine that is impaired for infection of neurons and provides better protection of mice than that obtained with a subunit vaccine. The strategy of altering the cell tropism of a virus is a new approach for a live attenuated vaccine. PMID- 26559849 TI - Retraction of: Hosseinkhani H, et al.; DOI: 10.1089/ten.2006.0120. PMID- 26559848 TI - Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types. AB - Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR independent agents might provide a novel therapeutic approach for treating HCMV disease. IMPORTANCE: HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of concept for the use of natural products targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment. PMID- 26559851 TI - Association between various anthropometric measures of obesity and markers of subclinical atherosclerosis. AB - Central obesity is a known cardiovascular risk factor and measures of visceral obesity are known to predict atherosclerosis. This study sought to explore the association between various anthropometric measures and markers of subclinical atherosclerosis (MoSCA) among low risk healthy individuals. Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of Caucasian (38%), Afro American (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45-84 years, free from clinical cardiovascular disease. We performed a post hoc analysis of the limited access dataset of MESA subjects to evaluate the association between carotid intima media thickness and coronary artery calcium score (CACS), as MoSCA and various measures of obesity. Multivariable regression analyses adjusted for traditional cardiovascular risk factors, ethnicity and C-reactive protein were performed. Each unit increase in waist-hip ratio was strongly associated with increase in both common and internal carotid intima media thickness (beta: 0.12, 95% confidence interval (CI): 0.06 to 0.18, p < 0.001 and beta: 0.23, 95% CI: 0.03 to 0.43, p = 0.021, respectively). Measures of central obesity were superior to body mass index as demonstrated by their consistent association with each category of CACS when compared to the reference category (CACS = 0). Compared to body mass index, measures of visceral obesity were significantly associated with MoSCA in this multiethnic healthy population. Waist-hip ratio seems to be more consistent in its association with various MoSCA compared to other anthropometric measures. PMID- 26559850 TI - Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration. AB - AIM: Experimental autoimmune encephalomyelitis (EAE) is a CD4(+)-mediated autoimmune pathology of the central nervous system (CNS) that is used as a model for the study of the human neuroinflammatory disease, multiple sclerosis. During the development of EAE, auto-reactive Th1 and Th17 CD4(+) T cells infiltrate the CNS promoting inflammatory cells recruitment, focal inflammation and tissue destruction. In this sense, statins, agents used to lower lipid levels, have recently shown to exert interesting immunomodulatory function. In fact, statins promote a bias towards a Th2 response, which ameliorates the clinical outcome of EAE. Additionally, simvastatin can inhibit Th17 differentiation. However, many other effects exerted on the immune system by statins have yet to be clarified, in particular during neuroinflammation. Thus, the aim of this study was to investigate the effects of simvastatin on the development of experimental autoimmune encephalomyelitis. METHODS: Mice were immunized with MOG(35-55) and EAE severity was assessed daily and scored using a clinical scale. Cytokine secretion by mononuclear cells infiltrating the CNS was evaluated by flow cytometry. RESULTS: Simvastatin (5 mg/kg/day) improved clinical outcome, induced an increase in TGF-beta mRNA expression and inhibited IL-6, IL-12p40, IL-12p70, RANTES and MIP-1beta secretion (p < 0.05). This was accompanied by a significant decrease in CNS inflammatory mononuclear cell infiltration, with reduced frequencies of both Th1 and Th17 cells. Simvastatin inhibited the proliferation of T lymphocytes co-cultured with primary microglial cells. CONCLUSIONS: Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells. PMID- 26559852 TI - Current and developing strategies for monitoring and reversing direct oral anticoagulants in patients with non-valvular atrial fibrillation. AB - OBJECTIVE: In light of the increasing clinical utilization of the direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation, this review evaluates strategies for monitoring and reversing the anticoagulant effect of these agents. METHODS: We summarize the data currently available for laboratory monitoring and reversal of DOACs. Relevant literature was identified using search terms pertaining to oral anticoagulants, reversal agents, and laboratory monitoring using Pubmed, clinicaltrials.gov, and abstracts from recent major cardiovascular meetings. RESULTS: Significant user appeal for the DOACs stems from the reliable pharmacokinetics of these agents, which render routine laboratory monitoring unnecessary for general use, as well as lower rates of bleeding as compared to warfarin. However, readily available laboratory tests have not been clinically validated for use with these agents. The ability to measure the anticoagulant effect of a DOAC in selected situations (e.g. serious bleeding, overanticoagulation, emergent procedures, and compliance monitoring) remains an unmet clinical need. Further, there is a paucity of data to guide treatment in patients receiving DOACs who experience a serious hemorrhage. CONCLUSION: While evidence-based recommendations cannot be definitively provided for management of DOAC-related bleeding events at present, several targeted reversal agents are currently in development, and hold promise for solving this important clinical problem. PMID- 26559853 TI - The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia Reperfusion Injury in Male Rats. AB - BACKGROUND: Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. OBJECTIVE: To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. METHOD: SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (+/- dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. RESULTS: In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. CONCLUSION: Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR. PMID- 26559855 TI - Genetic and Environmental Effects on the Abdominal Aortic Diameter Development. AB - BACKGROUND: Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. OBJECTIVES: We aimed to assess heritable and environmental effects on the abdominal aortic diameter. METHODS: 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 +/- 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. RESULTS: Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. CONCLUSIONS: Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications. PMID- 26559854 TI - Pulmonary Embolism Mortality in Brazil from 1989 to 2010: Gender and Regional Disparities. AB - BACKGROUND: A significant variation in pulmonary embolism (PE) mortality trends have been documented around the world. We investigated the trends in mortality rate from PE in Brazil over a period of 21 years and its regional and gender differences. METHODS: Using a nationwide database of death certificate information we searched for all cases with PE as the underlying cause of death between 1989 and 2010. Population data were obtained from the Brazilian Institute of Geography and Statistics (IBGE). We calculated age-, gender- and region specific mortality rates for each year, using the 2000 Brazilian population for direct standardization. RESULTS: Over 21 years the age-standardized mortality rate (ASMR) fell 31% from 3.04/100,000 to 2.09/100,000. In every year between 1989 and 2010, the ASMR was higher in women than in men, but both showed a significant declining trend, from 3.10/100,000 to 2.36/100,000 and from 2.94/100,000 to 1.80/100,000, respectively. Although all country regions showed a decline in their ASMR, the largest fall in death rates was concentrated in the highest income regions of the South and Southeast Brazil. The North and Northeast regions, the lowest income areas, showed a less marked fall in death rates and no distinct change in the PE mortality rate in women. CONCLUSIONS: Our study showed a reduction in the PE mortality rate over two decades in Brazil. However, significant variation in this trend was observed amongst the five country regions and between genders, pointing to possible disparities in health care access and quality in these groups. PMID- 26559856 TI - Relating HIV testing patterns in Poland to risky and protective behaviour. AB - The aim of the study was to understand HIV testing patterns needed to improve access to early HIV diagnosis, and to investigate the spread of the virus in different populations. We examined prior testing history of individuals presenting for an HIV test across all 30 voluntary testing and counselling sites in Poland, 2008-2010 to determine factors associated with the testing rate using zero-truncated Poisson regression. Of 2397 persons presenting for an HIV test, 25 (1%) were HIV positive and 470 (19.6%) were repeat testers. The proportion of repeat testers was higher among men who have sex with men (MSM) at 37% (90/246), and people who inject drugs (PWID) at 32% (21/65). Higher testing rate was independently associated with exposure category (testing rate ratio, RR for MSM = 2.0, 95% CI 1.6-2.6, and 1.6, 0.9-2.6 for PWID), >5 sex partners (1.9, 1.4-2.7), high-risk partner (1.3, 1.1-1.6), urban residence (2.1, 1.3-3.5) and higher education attainment (1.1, 1.0-1.5). Inconsistent condom use with casual partners and sex under the influence of alcohol were associated with lower testing rates. There is a need to increase HIV testing uptake in Poland, especially among the rural population. Despite testing rates being higher among populations with higher risk of exposure to HIV (MSM and PWID), they still remain low, indicating the existence of barriers to testing. PMID- 26559857 TI - Stimulation of the Antioxidative and Antimicrobial Potential of the Blood Red Bracket Mushroom Pycnoporus sanguineus (Higher Basidiomycetes). AB - The antioxidative and antibacterial properties of low-molecular-weight secondary metabolite subfractions (ex-LMS) from cultures of Pycnoporus sanguineus cultivated under different temperature conditions (25 degrees C [ex-LMSa] and 30 degrees C [ex-LMSb]) were assessed. The antioxidative properties were studied using chemiluminometric measurement, an ABTS assay, and a DPPH reduction rate assay with Trolox and ascorbic acid as the control. The values noted for the ex LMSb were significantly higher than those for ex-LMSa: 97%, 52%, and 31% for chemiluminometric measurement, the ABTS assay, and the DPPH assay, respectively, at a concentration of 50 ug/mL. Half-maximal effective concentrations reached 4.17 ug/mL for chemiluminometric measurement, 47.25 ug/mL for the ABTS assay, and 51.46 ug/mL for DPPH assay. Toxicity tests against Vibrio fischeri yielded 99.8% for ex-LMSa and 99.85% for ex-LMSb. Antibacterial activity toward Staphylococcus aureus was observed in the ex-LMSb fractions (inhibition zone, 23.5 mm; minimum inhibitory concentration, 0.12 mg/mL). Scanning electron microscopy images exhibited severe disruption of the bacterial cells treated with ex-LMSb compared with the control. The results obtained suggest that the extracellular fluid isolated from P. sanguineus-submerged cultures might be a good source of antioxidative and antibacterial compounds. In addition, the increase in the culture temperature evidently enhanced the bioactive properties of the preparation. PMID- 26559858 TI - Significant Correlation between TLR2 Agonist Activity and TNF-alpha Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products. AB - In the US market, there is a variety of mushroom preparations available, even within the same species of mushroom. Nonetheless, little is known about whether species or the various extraction methods affect biological activity and potency of the immune modulatory activity of mushroom extracts. After discovering that protein-bound polysaccharide-K, a hot water extract from Trametes versicolor, was a potent Toll-like receptor (TLR)-2 agonist that stimulates both innate and adaptive immunity, this study was initiated to evaluate whether other medicinal mushroom products also have TLR2 agonist activity and immune-enhancing potential as measured by the induction of tumor necrosis factor (TNF)-alpha in J774.A1 murine macrophage cells. Furthermore, the products were divided by extraction method and species to determine whether these factors affect their immunomodulatory activity. The results showed that the majority (75%) of mushroom products tested had TLR2 agonist activity and that there was a significant correlation between TLR2 agonist activity and TNF-alpha induction potential in the mushroom products analyzed. In addition, the data demonstrated that hot water mushroom extracts are more potent than ground mushroom products in activating TLR2 and inducing TNF-alpha. These data provide evidence that extraction methods may affect the biological activity of mushroom products; thus, further studies are warranted to investigate the structural differences between various mushroom products. PMID- 26559859 TI - Hypolipidemic and Hepatic Steatosis Preventing Activities of the Wood Ear Medicinal Mushroom Auricularia auricula-judae (Higher Basidiomycetes) Ethanol Extract In Vivo and In Vitro. AB - Obesity, a rapidly growing threat to human health worldwide, is responsible for a large proportion of the total burden of disease. Therefore, obesity control could be a vital scheme to prevent many diseases. The aim of this study was to examine the activities and mechanism of Auricularia auricula-judae 70% ethanol extract (AAE) in preventing hypolipidemic and hepatic steatosis. A normal diet (ND) and a high-fat diet (HFD) with or without 0.1% (w/w), 0.3% (w/w), and 1% (w/w) AAE were given to male C57BL/6 mice. Plasma lipids and liver enzymes were measured and tissue sections of liver were examined. Further mechanistic studies of mouse 3T3 L1 adipocytes were performed in vitro by verifying triglyceride, glycerol, and glycerol-3-phosphate dehydrogenase activity and messenger RNA expression of adipogenic and lipogenic genes using reverse transcriptase polymerase chain reaction amplification. Body weight and adipose tissue mass were significantly reduced in mice fed an ND and a HFD plus AAE compared with mice fed an HFD. In AAE-supplemented groups, plasma lipids and liver enzymes decreased dose dependently. AAE suppressed the expression of adipogenic/lipogenic genes (PPARgamma, C/EBPalpha, FAS) in 3T3-L1 cells without cytotoxicity. These findings suggest that AAE may reduce the risk of hepatic steatosis by modulating plasma lipids via the regulation of adipogenic/lipogenic transcriptional factors. AAE may have interesting applications to improve plasma lipids and liver enzymes. PMID- 26559860 TI - Chemical Composition and Medicinal Value of the New Ganoderma tsugae var. jannieae CBS-120304 Medicinal Higher Basidiomycete Mushroom. AB - In this research, the chemical composition and anticancer and antioxidant activity of the new medicinal mushroom Ganoderma tsugae var. jannieae CBS-120304 were evaluated. The chemical composition assay includes amounts of total carbohydrates and proteins, amino acids, fatty acids, micro- and macroelements, and vitamins. The investigated medicinal mushroom seemed to be a rich source of nutritional components. Mycelium accumulated more than 2-fold more total protein compared with the fruiting body and reached 37% and 16% of dry weight, respectively. Carbohydrate content in the fruiting body seemed to be conspicuously higher than in the mycelium (50% of dry weight) and reached 80% of dry weight. Quantification of the identified fatty acids indicated that, in general, palmitic acid, oleic acid, and linoleic acid were the major fatty acids. Toxic elements, such as silver, arsenic, cadmium, and mercury, were found only in trace amounts in mycelium and were not detected in the fruiting body. Furthermore, the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay was used to evaluate antioxidant activity. The highest radical scavenging activity was 9.0 mg/mL (65.9%) by ethanol extract. In addition, mycelial extracts were tested to inhibit MCF7 breast cancer cells. Ganoderma tsugae var. jannieae ethyl acetate extract (GTEAE) extract showed high potential by inhibiting reporter activity by more than 70%. Results demonstrated that GTEAE had a strong effect on inhibitory protein kappaBetaalpha level in the higher concentration used (200 gg/mL), which could be compared with the effect of parthenolide. Furthermore, GTEAE demonstrated strong inhibition of IkappaBetaalpha phosphorylation. PMID- 26559861 TI - Submerged Cultivation of Mycelium with High Ergothioneine Content from the Culinary-Medicinal Golden Oyster Mushroom, Pleurotus citrinopileatus (Higher Basidiomycetes). AB - The optimization of submerged culture of the culinary-medicinal golden oyster mushroom, Pleurotus citrinopileatus, was studied using a one-factor-at-a-time, two-stage stimulation and central composite rotatable design to produce mycelia with high ergothioneine content. The optimal culture conditions for mycelia harvested at day 22 were a temperature of 25 degrees C, an inoculation ratio of 5%, 2% glucose, 0.5% yeast extract, and adjustment of the initial pH value to 10. The biomass and ergothioneine content were 8.28 g/L and 10.65 mg/g dry weight (dw), respectively. The addition of an amino acid precursor increased the ergothioneine content of mycelia; cysteine was the most effective. In addition, the results obtained from central composite rotatable design showed that the recommended combination for cysteine, histidine, and methionine was 8, 4, and 0.5 mmol/L, respectively. The predicted ergothioneine content was 13.90 mg/g dw, whereas the experimental maximal ergothioneine content was 14.57 mg/g dw. With the addition of complex precursors and under optimal culture conditions, mycelia harvested at days 16-20 had higher ergothioneine content. Accordingly, the information obtained could be used to produce mycelia with high ergothioneine content. PMID- 26559862 TI - Hot Water Extracts of the Royal Sun Mushroom, Agaricus brasiliensis (Higher Basidiomycetes), Inhibit Platelet Activation via the P2Y1 Receptor. AB - Hot water extracts of the medicinal mushroom Agaricus brasiliensis were investigated for their inhibition of platelet aggregation. The extracts significantly inhibited human platelet aggregation induced by adenosine 5' diphosphate (ADP), but not by collagen or thrombin receptor-activating peptide. The extracts also had a significant inhibitory effect on shape change and intracellular calcium mobilization induced by ADP via inhibition of ADP binding to the P2Y1 receptor. In addition, oral administration of the extracts resulted in prolonged tail bleeding time in mice. The marked antiplatelet activity of the mushroom extracts involving the P2Y1 receptor suggests their potential therapeutic use against vascular disorders. PMID- 26559863 TI - A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps cicadae (Ascomycetes) in Rats. AB - Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food. PMID- 26559864 TI - Bioinformatic Identification of Potential MicroRNAs and Their Targets in the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Higher Basidiomycetes). AB - MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNA molecules that negatively regulate gene expression at the transcriptional or the post transcriptional level. Although a large number of miRNAs have been identified in many species, especially model plants and animals, miRNAs in fungi remain largely unknown. In this study, based on a database of expressed sequence tags in Ganoderma lucidum, 89 potential miRNAs were identified using computational methods. Real-time polymerase chain reaction analysis of miRNA-like samples prepared from G. lucidum at different development stages revealed that miRNA-like RNAs were differentially expressed in different stages. Furthermore, a total of 28 potential targets were found based on near-perfect or perfect complementarity between the randomly selected 9 miRNA-like RNAs and the target sequences, and potential targets for G. lucidum miRNA-like RNAs were predicted. Finally, we studied the expression pattern of 4 target genes in 3 different development stages of G. lucidum to further understand the mechanism of interaction between miRNA-like RNAs and their target genes. Our analysis paves the way toward identifying fungal miRNA-like RNAs that might be involved in various physiological and cellular differentiation processes. PMID- 26559865 TI - Familial Waldenstrom's macroglobulinemia and relation to immune defects, autoimmune diseases, and haematological malignancies--A population-based study from northern Sweden. AB - BACKGROUND: Waldenstrom's macroglobulinemia (WM) is a rare lymphoprolipherative disorder with geographic and ethnic disparities in incidence. The cause of WM remains mostly unknown although a role for genetic, immune-related, and environmental factors has been suggested. Most cases of WM are sporadic although familial cases occur. AIM: This study estimated the incidence of WM in northern Sweden and identified and described patients with familial WM in this area. PATIENTS AND METHODS: The Swedish and Northern Lymphoma Registry, the Swedish Cancer Registry (1997-2011), and medical records were used to identify patients with WM in two counties (Norrbotten and Vasterbotten) in northern Sweden and to calculate the overall age-adjusted incidence (2000-2012). We identified 12 families with a family history of WM, IgM monoclonal gammophathy (MGUS), and/or multiple myeloma (MM). RESULTS: In Norrbotten and Vasterbotten, the age-adjusted incidence of WM/LPL is 1.75 and 1.48 per 100,000 persons per year, respectively (2000-2012), rates that are higher than the overall incidence of WM/LPL in Sweden (1.05 per 100,000 persons per year; 2000-2012). Autoimmune diseases and other haematological malignancies in the medical history (their own or in relatives) were reported in 9/12 and 5/12 families, respectively. A high proportion of abnormal serum protein electrophoresis was found in the relatives; 12/56 (21%) had a MGUS and 13/56 (25%) showed abnormalities in the immunoglobulin levels (i.e. subnormal levels and poly/oligoclonality). CONCLUSION: The incidence of WM in Norrbotten and Vasterbotten counties was higher than expected. We found a strong correlation between autoimmune/inflammatory diseases, other haematological malignancies, and familial WM and a high frequency of serum immunoglobulin abnormalities in the relatives of the WM patients, findings that strengthen the hypothesis that the aetiology of WM depends on both immune-related and genetic factors. PMID- 26559866 TI - Prevalence of Mental Health Illness among Patients with Adult-Onset Strabismus. AB - BACKGROUND: Children diagnosed with some forms of strabismus were recently found to have an increased risk of developing mental illness by early adulthood. The purpose of this case-controlled study was to determine if adults with non paralytic forms of strabismus are similarly at an elevated risk for developing mental illness. METHODS: The medical records of all patients diagnosed as adults (>= 19 years of age) with convergence insufficiency (CI) (n = 118), divergence insufficiency (DI) (n = 80), and small angle hypertropia (HT (n = 99) from January 1, 1985, through December 31, 2004, were retrospectively reviewed. Each case was compared with a sex- and birth date-matched non-strabismic control. The medical records were reviewed for mental health diagnoses, including inpatient and outpatient encounters, psychiatric ER visits, and medication use. RESULTS: Mental health disorders were diagnosed in 65 (55.1%) patients with CI compared to 54 (45.8%) controls (p = 0.15), in 51 (63.8%) patients with DI compared to 42 (52.5%) controls (p = 0.15), and in 63 (63.6%) patients with HT compared to 57 (57.6%) controls (p = 0.38). CI patients were not more likely to have mental health disorders than their controls (p = 0.15). Mental health hospitalizations (p = 0.02), psychiatric medication use (p = 0.04), and unspecified anxiety disorders (p = 0.03) were higher in DI patients compared to controls. HT patients were found to have more generalized anxiety disorders (p = 0.003) than controls. CONCLUSIONS: Adults with some forms of strabismus (DI and HT) appear to have an increased risk of mental illness and its comorbidities, compared to age- and gender-matched non-strabismic controls. PMID- 26559867 TI - Effect of Horizontal Strabismus Surgery on the Refractive Status. AB - PURPOSE: To evaluate the effects of horizontal strabismus surgery on the refractive and astigmatic status of eyes following horizontal muscle surgery using double-angle vector analysis. MATERIALS AND METHODS: This was a retrospective analysis of 137 patients (250 eyes) conducted between February 1997 and October 2010 in patients who had unilateral or bilateral recession or monocular recession and/or underwent resection of horizontal muscles by a single surgeon. Refraction data were obtained at 1-2 weeks preoperative and at 4-6 weeks and 4-6 months postoperative. Surgically induced refractive changes were calculated using double-angle vector analysis. RESULTS: The mean change in the spherical equivalent (SE) of the refraction was 0.23 +/- 0.78 D for surgically induced refractive changes at 4-6 weeks postoperative (SIRC1; p < 0.0001) and 0.14 +/- 0.85 D (p = 0.018) for surgically induced refractive changes at 4-6 months postoperative (SIRC2), indicating a small shift in the myopic direction with regression at 4-6 months. The mean amplitudes of the induced cylinders were 0.072 +/- 1.22 D (p = 0.262) in SIRC1 and 0.20 +/- 1.14 D (p = 0.012) in SIRC2, and the mean axis of the induced plus cylinder was 21.74 degrees in SIRC1, indicating a small shift in the with-the-rule direction, but no statistically significant difference from zero (p = 0.331). The changes in the surgically induced refraction over time (SIRC d), ie, 0.05 +/- 0.64 in SE (p = 0.255) and 0.09 +/- 0.65 in the cylinder (p = 0.049), were stable. There was no significant correlation between the amounts of horizontal rectus muscle recession and/or resection and the cylinder power of individual induced astigmatism at 4-6 weeks after surgery (p = 0.266) and the myopic shift (p = 0.345). Moreover, there were no significant correlations between the ages of the patients and the spherical equivalent for SIRC1 (p = 0.858) and the induced cylinder for SIRC1 (p = 0.750). CONCLUSION: Horizontal rectus muscle surgery tended to induce a transient, statistically significant change in the spherical equivalent of refraction, with a myopic shift that was clinically not important. Our findings did not strongly support that the astigmatism induced changes. There was no correlation between the amount of recession and/or resection and the amount of induced refractive error. PMID- 26559868 TI - Esotropia in Children with Ventricular-Peritoneal Shunts. AB - PURPOSE: Compared with the general population, patients with hydrocephalus are more likely to have strabismus. This study was undertaken to examine characteristics and outcomes of children with esotropia and ventricular peritoneal shunt placement due to hydrocephalus. METHODS: This is a retrospective chart review of all pediatric patients with esotropia and a history of ventricular-peritoneal shunt placement seen by our pediatric ophthalmology service between January 2000 and December 2010. RESULTS: Sixteen patients between the age of 3 months and 5.6 years met study criteria. Nine were premature and all but one of the patients had developmental delay. Although all patients had a ventricular-peritoneal shunt, the diagnosis leading to shunt placement was intraventricular hemorrhage or congenital hydrocephalus in 75% of the patients. In all but 3 patients the hydrocephalus was diagnosed before the esotropia. Ten children had congenital esotropia and 6 had acquired esotropia. Eleven of the 16 children required glasses: 5 had a myopic prescription and 6 had a hyperopic prescription. Treatment of the esotropia resulted in 9 patients (56%) with successful ocular alignment (<10 prism diopters) on their last visit: 7 underwent strabismus surgery and 2 were treated with glasses only. Of the 9 patients who had strabismus surgery, 6 had congenital esotropia and 3 had acquired esotropia. Among patients who underwent strabismus surgery, 78% had successful ocular alignment at their last visit. CONCLUSIONS: While acquired accommodative esotropia is more common in the general population, children with ventricular peritoneal shunts may be more likely to have congenital esotropia. Although developmental delay is very frequent, successful ocular alignment may be possible in this patient population. PMID- 26559869 TI - Effect of 3-Dimensional Central Stimuli on Near Point of Convergence. AB - AIM: Since an interaction between binocular disparity and the vergence system takes place in order to reduce retinal disparity, it is likely that vergence control, as measured with the near point of convergence (NPC), will be better if the target used for measurement has 3-dimensional (3-D) features in its most central parts. The aim of the present study was therefore to investigate if the NPC would give a better result using a fixation target with centrally placed 3-D features when compared with a two-dimensional (2-D) target. METHODS: Twenty-three asymptomatic subjects (2 men, 21 women; average age 30.0 years +/- 7.36 SD) who experienced diplopia when a fixation target was brought close to the eyes had their break point NPC measured using a modified RAF-ruler. A metal cube and a printed image of the cube were used as a 3-D and 2-D stimuli. The measurements were repeated 3 times in each subject for each test condition, for a total of 6 randomized NPC measurements. RESULTS: On average a significant difference in NPC (p = 0.0172) was found for break point NPC with a 3-D stimuli (mean: 7.27 cm +/- 2.37 SD), giving the better result as compared with a 2-D stimuli (mean: 8.02 cm +/- 2.82 SD). Comparing the most remote recorded NPC values of the 3 repeated measurements under each stimulus condition, a significant difference was found (p = 0.0159, t = 2.612) with 3-D stimuli giving the better result. CONCLUSION: The results of this study demonstrate the influence of binocular disparity stimuli on the vergence control as NPC was better if the target used for measurement had 3-D features in its most central parts. PMID- 26559870 TI - The Prevalence of Ptosis and Its Association with Amblyopia and Strabismus in 7 Year-Old Schoolchildren in Iran. AB - PURPOSE: To determine the prevalence of ptosis (congenital/acquired) in Iranian children aged 7 years and its relationship with amblyopia and strabismus. METHODS: Eight Iranian cities were selected for this cross-sectional study using multistage randomized cluster sampling. A number of primary schools were randomly selected in each city. All grade 1 students in each selected primary school underwent optometric examinations including the measurement of uncorrected and corrected visual acuity, cover test, and cycloplegic and non-cycloplegic refraction. RESULTS: Of 4614 selected students, 4106 students participated in the study (response rate = 89%). The prevalence of ptosis (congenital/acquired) was 1.41% (95% CI 1-1.83); 0.49% (95% CI 0.26-0.72) and 0.93% (95% CI 0.59-1.26) had unilateral and bilateral ptosis, respectively. The prevalence of ptosis had no significant correlation with sex (p = 0.810, OR = 1.07, 95% CI 0.59-1.97). The prevalence of amblyopia was 48.28% and 0.89% in students with and without ptosis, respectively. The prevalence of tropia was significantly higher in cases with bilateral ptosis (p < 0.001). The mean cylinder error was 1.63 +/- 1.72 and 0.44 +/- 0.60 in ptotic and non-ptotic eyes, respectively (p < 0.001). With-the-rule (WTR) astigmatism was significantly more prevalent in students with ptosis. CONCLUSION: We report the prevalence of ptosis (congenital/acquired) in children in Iran and the Middle East region for the first time. Amblyopia was considerably more prevalent in ptotic patients. We found a significant correlation between ptosis and tropia. Astigmatism, especially WTR stigmatism, was more prevalent in children with ptosis. PMID- 26559871 TI - Pseudo-Monocular Nystagmus Associated with Duane's Syndrome: Report of Two Cases. AB - PURPOSE: To present clinical findings and eye movement recordings of two children who had clinically apparent monocular nystagmus. METHODS: Full orthoptic and ophthalmological examination and eye movement recordings. RESULTS: An 8-year-old girl (patient 1) and a 13-month-old girl (patient 2) presented with right monocular nystagmus and right esotropia. A magnetic resonance imaging (MRI) scan of the brain obtained previously had been unremarkable for patient 2. Patient 1 had right amblyopia with visual acuity (VA) reduced to 20/400. Both patients had left abduction deficit and left palpebral fissure narrowing on adduction indicative of Duane's retraction syndrome. Patient 2 also had mild enophthalmos. Both patients had constant horizontal nystagmus in the right eye and very fine nystagmus in the left eye, which could only be detected on video and eye movement recordings. CONCLUSION: The existence of Duane's syndrome in both patients was masking the presence of nystagmus in the left eye, highlighting that detailed examination in this case can eliminate the need for neuroimaging. Interestingly, the dominant eye of both patients was on the side which was affected by Duane's syndrome, as there was less nystagmus in this eye. PMID- 26559872 TI - The Physiologist Ewald Hering (1834-1918): Curriculum vitae. PMID- 26559874 TI - MRSA in Croatia: prevalence and management. AB - Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, mortality and length of hospital stay. MRSA is a major pathogen in hospitals and an important pathogen in community infections with few severe and fatal cases. However, MRSA causes the majority of skin and soft tissue infections in the US. The burden of community MRSA is much smaller in Europe, but there are reports of livestock-associated MRSA (LA-MRSA) isolated from pigs and cattle causing significant infections in the people who are connected to these farms. MRSA has been present in Croatia for more than 45 years, and it exerts a different impact on health-care infections. A remarkable increase in MRSA percentage was noted in primarily sterile samples in 2002 (37%) in comparison to 2001 (31%). This percentage remained quite high until 2008, when the first signs of a reduced trend were observed. The lowest percentage was 22% in 2012. PMID- 26559875 TI - Cervical ripening before first trimester surgical evacuation for non-viable pregnancy. AB - BACKGROUND: Medications or mechanical dilators are often used to soften and dilate the cervix prior to surgical evacuation of the uterus for non-viable pregnancy, or miscarriage. The majority of miscarriages occur in the first trimester. The aim of cervical ripening is to reduce the possibility of injury to the uterus and cervix and improve the surgical ease of the procedure. Cervical ripening agents can have adverse effects and it is uncertain as to whether these risks outweigh the benefits of their use. OBJECTIVES: To systematically review the benefits and harms of using cervical ripening agents prior to surgical evacuation of non-viable pregnancy prior to 14 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015) and reference lists of retrieved papers. SELECTION CRITERIA: Randomised controlled trials (published in full-text form, or as abstracts only), which assessed the use of pharmacological or mechanical agents to ripen the cervix in women undergoing dilation and curettage or vacuum aspiration for non viable pregnancy at less than 14 weeks' gestation were eligible for inclusion. Cluster-randomised controlled trials and trials using a cross-over design were not eligible for inclusion.Unpublished randomised controlled trials and quasi randomised trials would have been eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data were checked for accuracy. MAIN RESULTS: We included nine trials with 469 women. A diverse set of medications and regimens were studied in these trials, making the comparisons available for meta-analysis limited. The comparisons draw data from six trials with 383 participants. All trials were relatively small and had several aspects of unclear risk of bias with few of this review's outcomes reported. Due to this, no data from three trials were able to be used despite them meeting inclusion criteria.We carried out four comparisons: isosorbide mononitrate or dinitrate compared with misoprostol; misoprostol compared with placebo; chemical dilation (use of medications) compared with mechanical dilation; and any cervical preparation compared with placebo.None of the included studies reported data on the review's primary outcome: cervical or uterine injury (perforation, laceration, creation of a false passage).No clear difference was shown between isosorbide compounds and misoprostol for the outcome need for manual cervical dilation (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.10 to 5.64; three trials, 150 women; Tau2 = 2.11; I2 = 69%), however the data were heterogenous. In terms of adverse effects, misoprostol was associated with more vomiting (RR 0.11, 95% CI 0.01 to 0.85; two trials, 120 women), however there were no clear differences between isosorbide compounds and misoprostol in relation to other reported adverse effects (headache, nausea or hypotension). The dosing regimens differed in terms of dose, number of administrations and route of administration in the different trials. Mechanical (Dilapan-S hygroscopic) dilators performed similarly to chemical dilators in a single trial (65 women) that measured difficulty in cervical dilation, excessive bleeding and adverse effects.Misoprostol was shown to be more effective than placebo for cervical ripening (reduced need for manual cervical dilation) (RR 0.14, 95% CI 0.08 to 0.26; one trial, 120 women), and surgical time was reduced when misoprostol was used (mean difference (MD) -3.15, 95% CI -3.59 to -2.70; one trial, 120 women). However, compared to placebo, misoprostol, was associated with more abdominal pain (RR 29.00, 95% CI 1.77 to 475.35; one trial, 120 women), although no clear differences in the risk of other adverse effects (nausea, vomiting, headache or fever) were observed between groups.There was no clear differences between chemical dilation and mechanical dilators for the outcomes: difficulty in cervical dilation, excessive bleeding or adverse effects.Compared with placebo, any cervical preparation reduced the need for manual cervical dilatation (average RR 0.25, 95% CI 0.07 to 0.89; two trials, 168 women; Tau2 = 0.67; I2 = 81%), and reduced surgical time (MD -2.55, 95% CI -3.67 to -1.43, two trials, 168 women; Tau2 = 0.63; I2 = 96%).None of the included trials reported on the review's other secondary outcomes, including: injury to bladder or bowel, miscarriage/preterm birth in a subsequent pregnancy, analgesia use after administration of ripening agent but before surgery, or analgesia use after surgery. AUTHORS' CONCLUSIONS: This review found no evidence to evaluate cervical ripening prior to first trimester surgical evacuation for miscarriage for reducing the rate of cervical or uterine injury, however, this may be because these outcomes are very rare. Cervical preparation was shown to reduce the need for manual cervical dilatation compared with placebo.Misoprostol and isosorbide mononitrate and dinitrate were similarly effective in ripening the cervix, however there was more vomiting with misoprostol. Mechanical (Dilapan-S hygroscopic) dilators performed similarly to chemical dilators.The nine studies included in this review were small and the methodological quality of the trials was mixed, and for the most part, not well-described; thus any conclusions drawn from the data included in this review must be treated with caution. Consequently, large, high-quality trials are required to determine whether the benefits of this treatment outweigh the risks. Further research should be powered to assess the rate of cervical and uterine injury between interventions. Future research should also guide clinicians in deciding whether the benefits of reduced manual cervical dilatation outweigh the risks of adverse effects associated with these agents (nausea, vomiting, headache, fever, diarrhoea and pain). Women's satisfaction and outcomes of future pregnancies should also be assessed. PMID- 26559876 TI - Sidney Blatt's Object Relations Inventory: Contributions and Future Directions. AB - In this article, we provide a historical overview of the Object Relations Inventory (ORI) and related methods for the assessment of object relations constructed by Sidney Blatt and colleagues (e.g., Blatt, Bers, & Schaffer, 1992 ; Blatt, Wein, Chevron, & Quinlan, 1979 ; Diamond, Kaslow, Coonerty, & Blatt, 1990 ). We clarify terminology that has been used inconsistently in the literature, especially by way of differentiating the methods used to collect descriptions of significant figures, such as the ORI and its predecessor, the Parental Description (PD) task, and the rating scales that Blatt and colleagues constructed to rate those descriptions. We provide a tabular summary of empirical studies of the measure and offer a critical review of those aspects of the instrument that require further empirical investigation and methodological rigor. PMID- 26559877 TI - Injury rate and injury patterns in FIS World Cup Alpine skiing (2006-2015): have the new ski regulations made an impact? AB - BACKGROUND: New regulations for ski equipment were implemented prior to the 2012/2013 season in the International Ski Federation (FIS) Alpine World Cup (WC). OBJECTIVE: To investigate the effect of the new ski regulations on the rate and pattern of injuries by comparing data before (2006-2012) and after the implementation (2012-2015). METHODS: Injuries were recorded on the basis of the FIS Injury Surveillance System (FIS ISS) through retrospective interviews at the end of each of the nine WC seasons. All acute injuries that required medical attention were registered. Exposure was calculated on the basis of the official result lists. RESULTS: The absolute injury rate (injuries/100 athletes/season) was lower in the three seasons after the new ski regulations compared with the six seasons before (risk ratio (RR) 0.74, 95% CI 0.63 to 0.87). This was also the case for the relative injury rate (injuries/1000 runs) (RR 0.76, 95% CI 0.59 to 0.98). These changes were evident for male skiers, not for female skiers. There was a lower absolute injury rate for upper body injuries (RR 0.56, 95% CI 0.43 to 0.77), while no difference was found for lower extremity injuries (RR 0.84, 95% CI 0.70 to 1.01). CONCLUSIONS: We found a lower rate of injuries in the three seasons after the new ski regulation compared with the six seasons before. However, the ability to draw conclusions on the effects of the equipment change in subgroups of sex, discipline or body part is restricted by the limited statistical power. PMID- 26559878 TI - Hepatitis B in rugby: is it time to revisit policy? PMID- 26559879 TI - User fee exemption policies in Mali: sustainability jeopardized by the malfunctioning of the health system. AB - In Mali, where rates of attendance at healthcare facilities remain far below what is needed, three user fee exemption policies were instituted to promote access to care. These related to HIV/AIDS treatment, as of 2004, caesarean sections, since 2005, and treatment of malaria in children under five and pregnant women, since 2007. Our qualitative study compared these three policies, looking at their implementation provisions, functioning and outcomes. In each healthcare facility, we analysed documentation and carried out three months of on-site observations. We also conducted a total of 254 formal and informal interviews with health personnel and patients. PMID- 26559880 TI - Development of Group A streptococcal vaccines: an unmet global health need. AB - Group A Streptococcus (GAS) infections are a significant global cause of morbidity and mortality. GAS diseases disproportionally affect those living in conditions characterized by poverty and social injustice, in both developing countries and in marginalized populations of industrialized nations. In Australia and New Zealand, GAS-associated Acute Rheumatic Fever (ARF) is a major cause of health inequality disproportionally affecting indigenous children. Recognition of these inequalities by the governments of Australia and New Zealand has resulted in the formation of a Trans-Tasman Coalition to Advance New Vaccines for group A Streptococcus (CANVAS). This review provides an update on the current status of GAS vaccine development, and describes global efforts by CANVAS and others to accelerate the development of GAS vaccines. PMID- 26559881 TI - A Multidimensional Rasch Analysis of the Functional Independence Measure Based on the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems National Database. AB - A number of studies have evaluated the psychometric properties of the Functional Independence Measure (FIMTM) using Rasch analysis, although none has done so using the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems National Database, a longitudinal database that captures demographic and outcome information on persons with moderate to severe traumatic brain injury across the United States. In the current study, we examine the psychometric properties of the FIM as represented by persons within this database and demonstrate that the FIM comprises three subscales representing cognitive, self-care, and mobility domains. These subscales were analyzed simultaneously using a multivariate Rasch model in combination with a time dependent concurrent calibration scheme with the goal of creating a raw score-to-logit transformation that can be used to improve the accuracy of parametric statistical analyses. The bowel and bladder function items were removed because of misfit with the motor and cognitive items. Some motor items exhibited step disorder, which was addressed by collapsing Categories 1-3 for Toileting, Stairs, Locomotion, Tub/Shower Transfers; Categories 1 and 2 for Toilet and Bed Transfers; and Categories 2 and 3 for Grooming. The strong correlations (r = 0.82-0.96) among the three subscales suggest they should be modeled together. Coefficient alpha of 0.98 indicates high internal consistency. Keyform maps are provided to enhance clinical interpretation and application of study results. PMID- 26559882 TI - Gray matter network disruptions and amyloid beta in cognitively normal adults. AB - Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Abeta42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Abeta42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Abeta42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Abeta42 CSF levels and single subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Abeta42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Abeta42 levels can be related to gray matter networks disruptions. PMID- 26559883 TI - The relationship between inflammatory markers and voxel-based gray matter volumes in nondemented older adults. AB - Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels have been found in negative correlations with brain structural measures including global and lobar volumes and the hippocampus. This study investigated the relationship between 10 peripheral IMs and voxel-based gray matter (GM) volumes in nondemented older adults (n = 463). Two proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-1beta) and 2 vascular IMs (vascular cellular adhesion molecule-1 and plasminogen activator inhibitor-1) were negatively correlated with regional GM volumes. TNF-alpha and interleukin-1beta were both significantly correlated with GM volumes in the left occipitotemporal area, left superior occipital gyrus, and left inferior parietal lobule; TNF-alpha was also significantly correlated with the bilateral medial prefrontal cortices and approached significance for the correlations with the bilateral hippocampi. Significant GM correlations with vascular cellular adhesion molecule-1 were located in the bilateral anterior cingulate cortices, and with plasminogen activator inhibitor-1 in the cerebellum and right hippocampus. The neuroanatomical correlation patterns of 2 proinflammatory cytokines and 2 vascular IMs might be reflective of the effects of neurodegenerative and vascular pathological processes in the ageing brain. PMID- 26559884 TI - Acid suppression therapy should be reevaluated; liposome technology may be a good replacement. PMID- 26559885 TI - Elevated CRP level could herald less efficient autologous conditioned serum (ACS) treatment. AB - Autologous conditioned serum (ACS) is a biologically based local treatment aiming to influence the cytokine imbalance and is used in a variety of orthopedic diseases and conditions. The ACS contains elevated levels of various anti inflammatory cytokines, such as IL-1 RA (receptor antagonist), IL-4 and IL-10 and several growth factors. It contains a combination of cytokines and growth factors, and their specific contribution to clinical effects have yet to be determined. Serum conditioned in that specific way does not always have the same content and concentration of the anti-inflammatory cytokines and growth factors. We hypothesize that ACS should not be prepared and administered if elevated C reactive protein (CRP) levels are present at the moment of obtaining the patient's blood because of the potential detrimental effect of elevated pro inflammatory cytokines in the same blood, namely IL-1 and TNF. We propose introduction of CRP measuring before any ACS treatment. The cut off value would be set at 5mg/dL as an usual value suggesting inflammation. Avoidance of collecting and administering ACS if elevated CRP is present would potentially eliminate low quality ACS. PMID- 26559886 TI - Treatment of HIV/AIDS associated cancers with immunotherapy targeting PD-1/PD-L1 instead of chemotherapy. AB - The role of immunodeficiency in the pathogenesis of both AIDS-defining and non AIDS defining cancers cannot be over-emphasized. Multiple studies and meta analyses show that risk of these malignancies exponentially rises as the CD4 cell counts fall. Furthermore, treatment of these cancers in patients who have HIV/AIDS is complex and challenging due to the underlying immunosuppression and risk for infections. Often, the diagnosis of some of these malignancies is made at the same time as the diagnosis of HIV/AIDS, which further complicates treatment decisions, especially when CD4 counts are extremely low. The risks of giving chemotherapy in the setting of severe immunosuppression warrants a paradigm shift in how we should be treating malignancies in patients with HIV/AIDS. We hypothesize and propose that alongside combination antiretroviral therapy (cART), some patients with HIV/AIDS associated malignancies should be treated with immunotherapy targeting PD-1/PD-L1 pathway rather than chemotherapy. The rationale and basis for the new approach is presented. PMID- 26559887 TI - Exercise and rehabilitation delivered through exergames in older adults: An integrative review of technologies, safety and efficacy. AB - BACKGROUND: There has been a rapid increase in research on the use of virtual reality (VR) and gaming technology as a complementary tool in exercise and rehabilitation in the elderly population. Although a few recent studies have evaluated their efficacy, there is currently no in-depth description and discussion of different game technologies, physical functions targeted, and safety issues related to older adults playing exergames. OBJECTIVES: This integrative review provides an overview of the technologies and games used, progression, safety measurements and associated adverse events, adherence to exergaming, outcome measures used, and their effect on physical function. METHODS: We undertook systematic searches of SCOPUS and PubMed databases. Key search terms included "game", "exercise", and "aged", and were adapted to each database. To be included, studies had to involve older adults aged 65 years or above, have a pre-post training or intervention design, include ICT-implemented games with weight-bearing exercises, and have outcome measures that included physical activity variables and/or clinical tests of physical function. RESULTS: Sixty studies fulfilled the inclusion criteria. The studies had a broad range of aims and intervention designs and mostly focused on community-dwelling healthy older adults. The majority of the studies used commercially available gaming technologies that targeted a number of different physical functions. Most studies reported that they had used some form of safety measure during intervention. None of the studies reported serious adverse events. However, only 21 studies (35%) reported on whether adverse events occurred. Twenty-four studies reported on adherence, but only seven studies (12%) compared adherence to exergaming with other forms of exercise. Clinical measures of balance were the most frequently used outcome measures. PEDro scores indicated that most studies had several methodological problems, with only 4 studies fulfilling 6 or more criteria out of 10. Several studies found positive effects of exergaming on balance and gait, while none reported negative effects. CONCLUSION: Exergames show promise as an intervention to improve physical function in older adults, with few reported adverse events. As there is large variability between studies in terms of intervention protocols and outcome measures, as well as several methodological limitations, recommendations for both practice and further research are provided in order to successfully establish exergames as an exercise and rehabilitation tool for older adults. PMID- 26559888 TI - Embryo development in association with asymbiotic seed germination in vitro of Paphiopedilum armeniacum S. C. Chen et F. Y. Liu. AB - This paper documents the key anatomical features during the development of P. armeniacum zygotic embryos and their ability to germinate asymbiotically in vitro. This study also examines the effect of media and seed pretreatments on seed germination and subsequent seedling growth. Seeds collected from pods 45 days after pollination (DAP) did not germinate while 95 DAP seeds displayed the highest seed germination percentage (96.2%). Most seedlings (50%) developed to stage 5 from 110 DAP seeds whose compact testa had not yet fully formed. Suspensor cells were vacuolated, which enabled the functional uptake of nutrients. The optimum basal medium for seed germination and subsequent protocorm development was eighth-strength Murashige and Skoog (1/8MS) for 95 DAP seeds and 1/4MS for 110 DAP seeds. Poor germination was displayed by 140 DAP seeds with a compact testa. Pretreatment of dry mature seeds (180 DAP) with 1.0% sodium hypochlorite solution for 90 min or 40 kHz of ultrasound for 8 min improved germination percentage from 0 to 29.2% or to 19.7%, respectively. Plantlets that were at least 5 cm in height were transplanted to a Zhijing stone substrate for orchids, and 85.3% of plantlets survived 180 days after transplanting. PMID- 26559890 TI - Single florescent nanodiamond in a three dimensional ABEL trap. AB - Three dimensional single particle trapping and manipulation is an outstanding challenge in various fields ranging from basic physics to life sciences. By monitoring the response of a trapped particle to a designed environment one can extract its characteristics. In addition, quantum dynamics of a spatially scanned well-known particle can provide environmental information. Precise tracking and positioning of such a particle in aqueous environment is crucial task for achieving nano-scale resolution. Here we experimentally demonstrate three dimensional ABEL trap operating at high frequency by employing a hybrid approach in particle tracking. The particle location in the transverse plane is detected via a scanning laser beam while the axial position is determined by defocused imaging. The scanning of the trapped particle is accomplished through a nano positioning stage integrated to the trap platform. PMID- 26559889 TI - Habitat use and diel vertical migration of bigeye thresher shark: Overlap with pelagic longline fishing gear. AB - Pelagic longliners targeting swordfish and tunas in oceanic waters regularly capture sharks as bycatch, including currently protected species as the bigeye thresher, Alopias superciliosus. Fifteen bigeye threshers were tagged with pop-up satellite archival tags (PSATs) in 2012-2014 in the tropical northeast Atlantic, with successful transmissions received from 12 tags for a total of 907 tracking days. Marked diel vertical movements were recorded on all specimens, with most of the daytime spent in deeper colder water (mean depth = 353 m, SD = 73; mean temperature = 10.7 degrees C, SD = 1.8) and nighttime spent in warmer water closer to the surface (mean depth = 72 m, SD = 54; mean temperature = 21.9 degrees C, SD = 3.7). The operating depth of the pelagic longline gear was measured with Minilog Temperature and Depth Recorders (TDRs), and the overlap with habitat utilization was calculated. Overlap is taking place mainly during the night and is higher for juveniles. The results presented herein can be used as inputs for Ecological Risk Assessments for bigeye threshers captured in oceanic tuna fisheries, and serve as a basis for efficient management and conservation of this vulnerable shark species. PMID- 26559891 TI - The lanthipeptides of Bacillus methylotrophicus and their association with genomic islands. AB - Bacillus methylotrophicus strains are known for their potential as plant-growth promoters and as microbial pesticides that effectively control plant diseases caused by bacteria and fungi. Over the past few years, a wide diversity of their secondary metabolites has been extensively characterized. Among these are the RiPPs lanthipeptides, which are an important and growing group of notable compounds. The increasing interest in B. methylotrophicus species, accompanied by the development of high throughput sequencing techniques, has resulted in a substantial number of full genomes being available. Here, an in silico analysis was performed on these genomes in order to survey the presence of lanthipeptide biosynthetic clusters. It was found that the pan genome of B. methylotrophicus only encoded the biosynthesis of mersacidin and amylolysin, which are lanthipeptides with antibacterial activity. However, the amylolysin gene cluster identified was comprised of more genetic elements than those previously described, and it had certain features of two-peptide lantibiotics. Additionally, it was also established that the association of lanthipeptides with genomic islands (GIs) was not confined to mersacidin. This was also found for the amylolysin cluster as well as other class I and class II lanthipeptides, supporting the idea that their production is probably related to functional adaptation. PMID- 26559892 TI - Synchrony is Key: Complex Spike Inhibition of the Deep Cerebellar Nuclei. AB - The control of deep cerebellar nuclear (DCN) neuronal firing is central to cerebellar function but is not well understood. The large majority of synapses onto DCN neurons derive from Purkinje cells (PCs), suggesting that PC activity is an important determinant of DCN firing; however, PCs fire both simple and complex spikes (CSs), and little is known about how the latter's action affects DCN activity. Thus, here, we explored the effects of CSs on DCN activity. CSs were recorded from PC arrays along with individual DCN neurons. Presumed synaptically connected PC-DCN cell pairs were identified using CS-triggered correlograms of DCN activity, which also showed that CS activity was associated with a predominantly inhibitory effect on DCN activity. The strength of the CS effect varied as a function of synchrony, such that isolated CSs produced only weak inhibition of DCN activity, whereas highly synchronous CSs caused a larger drop in firing levels. Although the present findings were obtained in anesthetized animals, similar CS synchrony levels exist in awake animals, and changes in synchrony level have been observed in association with movements in awake animals. Thus, the present data suggest that synchronous CS activity may be a mechanism for shaping DCN output related to motor commands. PMID- 26559894 TI - 'Under the Dome' on Chinese air pollution, a documentary by Chai Jing. PMID- 26559893 TI - Mosaic Expression of Thyroid Hormone Regulatory Genes Defines Cell Type-Specific Dependency in the Developing Chicken Cerebellum. AB - The cerebellum is a morphologically unique brain structure that requires thyroid hormones (THs) for the correct coordination of key cellular events driving its development. Unravelling the interplay between the multiple factors that can regulate intracellular TH levels is a key step to understanding their role in the regulation of these cellular processes. We therefore investigated the regional/cell-specific expression pattern of TH transporters and deiodinases in the cerebellum using the chicken embryo as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), L-type amino acid transporter 1 (LAT1) and organic anion transporting polypeptide 1C1 (OATP1C1) as well as the inactivating type 3 deiodinase (D3) in the fourth ventricle choroid plexus, suggesting a possible contribution of the resulting proteins to TH exchange and subsequent inactivation of excess hormone at the blood-cerebrospinal fluid barrier. Exclusive expression of LAT1 and the activating type 2 deiodinase (D2) mRNA was found at the level of the blood-brain barrier, suggesting a concerted function for LAT1 and D2 in the direct access of active T3 to the developing cerebellum via the capillary endothelial cells. The presence of MCT8 mRNA in Purkinje cells and cerebellar nuclei during the first 2 weeks of embryonic development points to a potential role of this transporter in the uptake of T3 in central neurons. At later stages, together with MCT10, detection of MCT8 signal in close association with the Purkinje cell dendritic tree suggests a role of both transporters in TH signalling during Purkinje cell synaptogenesis. MCT10 was also expressed in late born cells in the rhombic lip lineage with a clear hybridisation signal in the outer external granular layer, indicating a potential role for MCT10 in the proliferation of granule cell precursors. By contrast, expression of D3 in the first-born rhombic lip-derived population may serve as a buffering mechanism against high T3 levels during early embryonic development, a hypothesis supported by the pattern of expression of a fluorescent TH reporter in this lineage. Overall, this study builds a picture of the TH dependency in multiple cerebellar cell types starting from early embryonic development. PMID- 26559895 TI - The persistent under-utilization of epilepsy surgery. PMID- 26559896 TI - Response to "The persistent under-utilization of epilepsy surgery". PMID- 26559897 TI - Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis. AB - Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. PMID- 26559898 TI - Obesity in adolescents with intellectual disability: Prevalence and associated characteristics. AB - OBJECTIVE: Studies from a number of countries have indicated an increased risk of obesity in adolescents with intellectual disability. Whether risk factors for adults with intellectual disability apply to adolescents however is uncertain. This study examines obesity in a community sample of adolescents with intellectual disability in Australia, and investigates risk factors associated with obesity and overweight. METHODS: A cross-sectional survey and medical record review on 261 adolescents with intellectual disability attending special education facilities in South-East Queensland, Australia between January 2006 and September 2010 was conducted. Information on age, gender, weight, height, syndrome specific diagnoses, problematic behaviours, mobility, taking psychotropic or epileptic medication, and perceived household financial difficulties was collected. Body mass index (BMI) was calculated and participants categorised as normal/underweight, overweight or obese according to the International Obesity Taskforce definitions. RESULTS: Overall 22.5% (95% CI: 17.8 28.0%) of adolescents were obese, and 23.8% (95% CI: 19.0-29.4%) were overweight, a marked increase compared to Australian norms. Adolescents with Down syndrome were more likely to be obese than other participants (odds ratio=3.21; 95% CI: 1.41-7.30). No association was found with other risk factors examined. CONCLUSIONS: Prevalence of obesity and overweight were increased compared to general Australian adolescents. The only significant risk factor was the presence of Down syndrome. These findings reinforce the need for a health policy and practice response to obesity that is inclusive of individuals with intellectual disability. PMID- 26559900 TI - Safety evaluation of AMP deaminase from Aspergillus oryzae. AB - Adenosine-5'-monophosphate (AMP) deaminase is an enzyme used to increase concentrations of 5'-inosine monophosphate in certain foods and beverages for flavoring purposes. One commercial source of this enzyme is Aspergillus oryzae, a filamentous fungus with a history of safe use in Asia as a fermentation organism used in the production of miso sauce and sake liquors. Noting the use of the enzyme in food intended for human consumption and potential presence at trace levels in finished goods, a series of safety studies including an in vitro Ames test and chromosome aberration assay with Chinese hamster lung fibroblasts were conducted along with a 90-day oral toxicity study in rats. AMP deaminase showed no evidence of genotoxicity in the in vitro tests. Following gavage administration of Sprague-Dawley rats at dosages of 19.8, 198.4, or 1984 mg total organic solids (TOS)/kg body weight (bw)/day for 90 days, no adverse effects on body weight gain, food consumption, hematology, clinical chemistry, urinalysis, ophthalmological and histopathological examinations were observed. The no observed-adverse-effect level was considered to be 1984 mg TOS/kg bw/day, the highest dose tested. Results of the genotoxicity studies and subchronic rat study support the safe use of AMP deaminase produced from A. oryzae in food production. PMID- 26559901 TI - Simultaneous attenuation of pharmaceuticals, organic matter, and nutrients in wastewater effluent through managed aquifer recharge: Batch and column studies. AB - Batch and column experiments were conducted to evaluate the removal of organic matter, nutrients, and pharmaceuticals and to identify the removal mechanisms of the target contaminants. The sands used in the experiments were obtained from the Youngsan River located in South Korea. Neutral and cationic pharmaceuticals (iopromide, estrone, and trimethoprim) were removed with efficiencies greater than 80% from different sand media during experiments, due to the effect of sorption between sand and pharmaceuticals. However, the anionic pharmaceuticals (sulfamethoxazole, ketoprofen, ibuprofen, and diclofenac) were more effectively removed by natural sand, compared to baked sand. These observations were mainly attributed to biodegradation under natural conditions of surface organic matter and ATP concentrations. The removal of organic matter and nitrogen was also found to increase under biotic conditions. Therefore, it is indicated that biodegradation plays an important role and act as major mechanisms for the removal of organic matter, nutrients, and selected pharmaceuticals during sand passage and the managed aquifer recharge, which is an effective treatment method for removing target contaminants. However, the low removal efficiencies of pharmaceuticals (e.g., carbamazepine and sulfamethoxazole) require additional processes (e.g., AOPs, NF and RO membrane), a long residence time, and long travel distance for increasing the removal efficiencies. PMID- 26559899 TI - Multi-Toxin Resistance Enables Pink Bollworm Survival on Pyramided Bt Cotton. AB - Transgenic crops producing Bacillus thuringiensis (Bt) proteins kill key insect pests, providing economic and environmental benefits. However, the evolution of pest resistance threatens the continued success of such Bt crops. To delay or counter resistance, transgenic plant "pyramids" producing two or more Bt proteins that kill the same pest have been adopted extensively. Field populations of the pink bollworm (Pectinophora gossypiella) in the United States have remained susceptible to Bt toxins Cry1Ac and Cry2Ab, but field-evolved practical resistance to Bt cotton producing Cry1Ac has occurred widely in India. Here we used two rounds of laboratory selection to achieve 18,000- to 150,000-fold resistance to Cry2Ab in pink bollworm. Inheritance of resistance to Cry2Ab was recessive, autosomal, conferred primarily by one locus, and independent of Cry1Ac resistance. We created a strain with high resistance to both toxins by crossing the Cry2Ab-resistant strain with a Cry1Ac-resistant strain, followed by one selection with Cry2Ab. This multi-toxin resistant strain survived on field collected Bt cotton bolls producing both toxins. The results here demonstrate the risk of evolution of resistance to pyramided Bt plants, particularly when toxins are deployed sequentially and refuges are scarce, as seen with Bt cotton and pink bollworm in India. PMID- 26559902 TI - RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response. AB - In response to an osmotic challenge, the synthesis of the antidiuretic hormone arginine vasopressin (AVP) increases in the hypothalamus, and this is accompanied by extension of the 3' poly(A) tail of the AVP mRNA, and the up-regulation of the expression of RNA binding protein Caprin-2. Here we show that Caprin-2 binds to AVP mRNAs, and that lentiviral mediated shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortens the AVP mRNA poly(A) tail at the same time as reducing transcript abundance. In a recapitulated in vitro system, we confirm that Caprin-2 over-expression enhances AVP mRNA abundance and poly(A) tail length. Importantly, we show that Caprin-2 knockdown in the hypothalamus decreases urine output and fluid intake, and increases urine osmolality, urine sodium concentration, and plasma AVP levels. Thus Caprin-2 controls physiological mechanisms that are essential for the body's response to osmotic stress. PMID- 26559903 TI - Use of Health Care Resources and Costs After Patient Nonattendance in Dermatology. PMID- 26559904 TI - Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders. AB - BACKGROUND: Observational studies show a strong association between delayed intestinal transit and the production of methane. Experimental data suggest a direct inhibitory activity of methane on the colonic and ileal smooth muscle and a possible role for methane as a gasotransmitter. Archaea are the only confirmed biological sources of methane in nature and Methanobrevibacter smithii is the predominant methanogen in the human intestine. AIM: To review the biosynthesis and composition of archaeal cell membranes, archaeal methanogenesis and the mechanism of action of statins in this context. METHODS: Narrative review of the literature. RESULTS: Statins can inhibit archaeal cell membrane biosynthesis without affecting bacterial numbers as demonstrated in livestock and humans. This opens the possibility of a therapeutic intervention that targets a specific aetiological factor of constipation while protecting the intestinal microbiome. While it is generally believed that statins inhibit methane production via their effect on cell membrane biosynthesis, mediated by inhibition of the HMG-CoA reductase, there is accumulating evidence for an alternative or additional mechanism of action where statins inhibit methanogenesis directly. It appears that this other mechanism may predominate when the lactone form of statins, particularly lovastatin lactone, is administered. CONCLUSIONS: Clinical development appears promising. A phase 2 clinical trial is currently in progress that evaluates the effect of lovastatin lactone on methanogenesis and symptoms in patients with irritable bowel syndrome with constipation. The review concludes with an outlook for the future and subsequent work that needs to be done. PMID- 26559905 TI - CD49d (ITGA4) expression is a predictor of time to first treatment in patients with chronic lymphocytic leukaemia and mutated IGHV status. AB - We investigated CD49d (also termed ITGA4) expression and its biological and clinical correlations in 415 patients with chronic lymphocytic leukaemia. CD49d expression was stable over the course of the disease. A high expression of CD49d (>30%) was found in 142/415 (34%) patients and was associated with progressive disease (advanced clinical stage, high serum lactate dehydrogenase or beta2 microglobulin levels; all p < 0.05) and aggressive disease biology (increased ZAP70 or CD38, unmutated IGHV, trisomy 12, mutations of NOTCH1 and SF3B1; all P < 0.05). A higher CD49d expression was also associated with a lower blood lymphocyte count and a higher number of lymphoid areas involved by the disease. Patients with high CD49d expression were treated more frequently (55% vs. 27%; P < 0.001) and earlier (median time to treatment [TTT] 65.4 months vs. not reached; P < 0.001) than those with low CD49d expression. However, no significant differences in response rates were observed. In the subgroup of patients with mutated IGHV, high CD49d expression was predictive of a shorter TTT while other markers, such as ZAP70 and CD38, were not. In conclusion, in this study CD49d expression correlated with high-risk CLL biomarkers and proved to be useful for separating patients with mutated IGHV into two different prognostic groups. PMID- 26559906 TI - Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an (18)F-Radiolabeled Water-Soluble Porphyrin. AB - Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an (18)F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors. PMID- 26559907 TI - Neurotoxicity, general anesthesia in young children, and a survey of current pediatric anesthesia practice at US teaching institutions. AB - BACKGROUND: Recent articles in both scholarly journals and the lay press about the topic of anesthetic related neurotoxicity have increased the awareness and discussion of this topic with parents and other pediatric medical specialties (i.e., surgeons, radiologists, and pediatricians). AIM: The purpose of the present study was to survey how a subset of pediatric anesthesia departments in the US have responded to the issue of anesthetic related neurotoxicity in terms of clinical practice, training and communication with other medical specialties, and the frequency and timing of discussions with families. METHODS: A survey consisting of 22 questions was sent to PALC (Pediatric Anesthesia Leadership Council) & PAPDA (Pediatric Anesthesia Program Directors Association) via SurveyMonkey. The survey was divided into sections on Anesthesia Faculty/Trainees, Parents and Non-Anesthesia Providers. Responses to the survey were solicited via email to PALC and PAPDA, and then followed up with reminders to individual emails using the mailing lists of both organizations. RESULTS: The results of this survey demonstrate that pediatric anesthesia programs around the US do not have a consistent approach in managing the topic of anesthesia-related neurotoxicity with pediatric anesthesiologists, anesthesiology residents, pediatric anesthesiology fellows and their non-anesthesia medical and surgical colleagues, as well as the discussion of this topic with parents. CONCLUSION: A significant need exists to provide information to other pediatric professionals and parents. A consistent message from all providers that includes what is known, and indeed more importantly what is not known may be a useful approach. PMID- 26559908 TI - Ruminal degradability and intestinal digestibility of individual amino acids in mixed diets with different crude protein levels measured by the modified in vitro three-step and mobile nylon bag technique. AB - The ruminal degradability and intestinal digestibility of dry matter (DM), crude protein (CP) and amino acids (AA) in three total mixed rations with different CP levels were estimated using the modified in vitro three-step procedure (TSP) and mobile nylon bag (MNB) technique on growing lambs. The ruminal effective degradability of DM and CP did not respond with increasing dietary CP level. However, the intestinal digestibility of DM was significantly increased with increasing dietary CP level estimated by TSP (P < 0.05) or MNB method (P < 0.01). Intestinal digestibility coefficients of CP determined by TSP were lower than those of the MNB method. Histidine was extensively degraded by rumen micro organisms, while tyrosine was the most anti-degradable AA among the samples. The ruminal AA degradability exhibited no significant differences except for threonine, tryptophan, alanine, aspartic acid and proline for the three diets. Similarly, only a few AAs (i.e. histidine, methionine, tryptophan, aspartic acid and cysteine in TSP; histidine, tryptophan, aspartic acid and serine in MNB) had significant differences in their intestinal digestibility; in addition, values of MNB were lower than that of the TSP method, indicating that intestinal digestibility of DM seems to be overestimated in TSP, while that of CP might be overestimated in the MNB method. PMID- 26559909 TI - Processing insect abundance: trading and fishing of zazamushi in Central Japan (Nagano Prefecture, Honshu Island). AB - BACKGROUND: This article presents the links between technique, commerce and consumption in fishing for zazamushi, a mixture of aquatic insect larvae sold as food souvenirs in Japan. Since zazamushi are mainly collected for economic reasons, we suggest that demand for them has incited technical development among collectors in order to fish more insects. METHODS: Several fishermen and traders were interviewed in semi-directed interviews about their practices and knowledge. To understand the passage from a faunal composition to a commercial composition, our research follows a fishing session closely, as well as the selection of insects that follows it. The insects collected were separated from inanimate matter, then identified, counted and weighed at each stage of the process. RESULTS: Our results suggest that the current technique corresponds to an evolution in subsistence and recreational collecting towards a more systematic fishing of the insects, the aim of which is commercial. In their response to trade issues, the collectors have moved away from the banks to fish the insects in the river current, thus increasing the amount of one species captured compared to another. Although the technique is efficient (and similar to other harvesting techniques), it requires the thorough sorting of organic debris and insects (in our example, the catch contains approximately 78 % of inanimate matter and 22 % of insects, of which 3.29 % are retained for consumption, i.e., less than 2 out of 100 insects). The selection of insects to be consumed takes place mainly during cleaning. This stage depends on traders and reflects the different compositions sold as souvenirs. CONCLUSIONS: Our research shows that the consumption of insects is not explained just by ecological factors that are favourable or unfavourable, but also by technological and economic factors related to their commerce. It suggests that the traders have gradually established the insects that are currently sold as zazamushi and that this commercial development may have had an influence on the preference for insects consumed. It also shows that the cleaning of the insects constitutes an important stage prior to their consumption, one that should not be underestimated. PMID- 26559910 TI - NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape. AB - Glioblastoma (grade IV glioma) is the most common and aggressive adult brain tumor. A better understanding of the biology of glioblastoma cells is crucial to identify molecular targets stimulating cell death. NPM1 (nucleophosmin) is a multifunctional chaperone that plays an important role in cancer development. Herein, NPM1 was analyzed by immunohistochemistry in human astrocytic gliomas. NPM1 was detected in all tumors but with a significantly higher staining intensity in grade IV than in low grade tumors. Depletion of NPM1 had only modest effects on the viability of U251MG, U1242MG, and U343MGa Cl2:6 glioma cells, despite alterations in nucleolar morphology. Glioma cell cultures depleted of NPM1 exposed to micromolar levels of actinomycin D were more prone to cell death (apoptosis) compared to cultures retaining NPM1. We had previously found that NPM1 binds to linker histone H1.5. Here we could show that silencing of H1.5 triggered glioma cell apoptosis as evidenced by a marked increase in both the numbers of cleaved caspase-3(+) cells and in the amounts of cleaved PARP. Enforced expression of NPM1 suppressed apoptosis in H1.5 depleted glioma cells. Although our studies would suggest little effectiveness of targeting NPM1 alone there could be potential using it as a combination treatment. PMID- 26559911 TI - The effect of abortion on having and achieving aspirational one-year plans. AB - BACKGROUND: Women commonly report seeking abortion in order to achieve personal life goals. Few studies have investigated whether an abortion enables women to achieve such goals. METHODS: Data are from the Turnaway Study, a prospective cohort study of women recruited from 30 abortion facilities across the US. The sample included women in one of four groups: Women who presented for abortion just over the facility's gestational limit, were denied an abortion and went on to parent the child (Parenting Turnaways, n = 146) or did not parent (Non Parenting Turnaways, n = 64), those who presented just under the facility's gestational limit and received an abortion (Near-Limits, n = 413) and those who presented in the first trimester and received an abortion (First Trimesters, n = 254). Participants were interviewed by telephone one week, six months and one year after they sought an abortion. We used mixed effects logistic regression to assess the relationship between receiving versus being denied abortion and having an aspirational one year goal and achieving it. RESULTS: The 757 participants in this analysis reported a total of 1,304 one-year plans. The most common one-year plans were related to education (21.3 %), employment (18.9 %), other (16.3 %), and change in residence (10.4 %). Most goals (80 %) were aspirational, defined as a positive plan for the next year. First Trimesters and Near-Limits were over 6 times as likely as Parenting Turnaways to report aspirational one-year plans [Adjusted Odds Ratio (AOR) = 6.37 and 6.56 respectively, p < 0.001 for both]. Among all plans in which achievement was measurable (n = 1,024, 87 %), Near Limits (45.6 %, AOR = 1.91, p = 0.003) and Non-Parenting Turnaways (47.9 %, AOR = 2.09, p = 0.026) were more likely to have both an aspirational plan and to have achieved it than Parenting Turnaways (30.4 %). CONCLUSIONS: These findings suggest that ensuring women can have a wanted abortion enables them to maintain a positive future outlook and achieve their aspirational life plans. PMID- 26559913 TI - Valid and reliable techniques for measuring fibrosis in patients with head and neck cancer postradiotherapy: A systematic review. AB - BACKGROUND: Fibrosis is a common side effect of radiotherapy for head and neck cancer. Although treatments for fibrosis have been developed, valid and reliable measurement tools are needed to verify their efficacy. The purpose of this review was to identify and appraise tools used to measure head and neck fibrosis. METHODS: Electronic databases were searched for primary research published through April 2014. Main search terms included head and neck cancer, radiotherapy, fibrosis, validity, and reliability. Methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two blinded raters conducted all assessments. Discrepancies were resolved by consensus. RESULTS: The search retrieved 534 unique citations. Nine studies met our inclusion criteria, representing 9 different tools. Only 1 tool was assessed for reliability and validity. QUADAS-2 revealed that all studies were at risk for bias. CONCLUSION: To date, there are no valid and reliable techniques for measuring fibrosis postradiotherapy for head and neck cancer, especially within the suprahyoid and pharyngeal regions. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E2322-E2334, 2016. PMID- 26559912 TI - Withdrawal of anticancer therapy in advanced disease: a systematic literature review. AB - BACKGROUND: Current guidelines set out when to start anticancer treatments, but not when to stop as the end of life approaches. Conventional cytotoxic agents are administered intravenously and have major life-threatening toxicities. Newer drugs include molecular targeted agents (MTAs), in particular, small molecule kinase-inhibitors (KIs), which are administered orally. These have fewer life threatening toxicities, and are increasingly used to palliate advanced cancer, generally offering additional months of survival benefit. MTAs are substantially more expensive, between L2-8 K per month, and perceived as easier to start than stop. METHODS: A systematic review of decision-making concerning the withdrawal of anticancer drugs towards the end of life within clinical practice, with a particular focus on MTAs. Nine electronic databases searched. PRISMA guidelines followed. RESULTS: Forty-two studies included. How are decisions made? Decision making was shared and ongoing, including stopping, starting and trying different treatments. Oncologists often experienced 'professional role dissonance' between their self-perception as 'treaters', and talking about end of life care. Why are decisions made? Clinical factors: disease progression, worsening functional status, treatment side-effects. Non-clinical factors: physicians' personal experience, values, emotions. Some patients continued treatment to maintain 'hope', often reflecting limited understanding of palliative goals. When are decisions made? Limited evidence reveals patients' decisions based upon quality of life benefits. Clinicians found timing withdrawal particularly challenging. Who makes the decisions? Decisions were based within physician-patient interaction. CONCLUSIONS: Oncologists report that decisions around stopping chemotherapy treatment are challenging, with limited evidence-based guidance outside of clinical trial protocols. The increasing availability of oral MTAs is transforming the management of incurable cancer; blurring boundaries between active treatment and palliative care. No studies specifically addressing decision making around stopping MTAs in clinical practice were identified. There is a need to develop an evidence base to support physicians and patients with decision making around the withdrawal of these high cost treatments. PMID- 26559915 TI - The impact of adjunctive complex fractionated atrial electrogram ablation and linear lesions on outcomes in persistent atrial fibrillation: a meta-analysis. AB - AIMS: In persistent atrial fibrillation (PsAF), success rates for pulmonary vein isolation (PVI) alone are limited and additional substrate modification is often performed. The two most widely used substrate-based strategies are the ablation of complex fractionated atrial electrograms (CFAE) and left atrial linear ablation (LALA) at the roof and mitral isthmus. However, it is unclear whether adjunctive CFAE ablation or LALA add significant benefit to PVI alone. We performed a meta-analysis to better gauge the benefit of adjunctive CFAE ablation and LALA in PsAF. METHODS AND RESULTS: Electronic databases were systematically searched. We included studies that examined the impact of CFAE ablation or LALA in addition to a PVI-based strategy on clinical outcomes in PsAF. We included both randomized and non-randomized studies. Totally 10 studies (n = 1821) were included: 6 evaluating CFAE ablation, 3 LALA, and 1 both approaches. In comparison with PVI alone, the addition of CFAE ablation [RR 0.86; 95% confidence intervals (CI) 0.64, 1.16; P = 0.32] or LALA (RR 0.64; 95% CI 0.37, 1.09; P = 0.10) offered no significant improvement in arrhythmia-free survival. However, adjunctive CFAE ablation was associated with significant increases (P < 0.05) and LALA non-significant increases in procedure and fluoroscopy times. CONCLUSION: In PsAF, the addition of CFAE ablation or LALA, in comparison with PVI alone, offers no significant improvement in arrhythmia-free survival. Furthermore, they are associated with increases in both procedural and fluoroscopy times. The optimal ablation strategy for PsAF is currently unclear and needs further refinement. PMID- 26559914 TI - Connectivity between the OFF bipolar type DB3a and six types of ganglion cell in the marmoset retina. AB - Parallel visual pathways originate at the first synapse in the retina, where cones make connections with cone bipolar cells that in turn contact ganglion cells. There are more ganglion cell types than bipolar types, suggesting that there must be divergence from bipolar to ganglion cells. Here we analyze the contacts between an OFF bipolar type (DB3a) and six ganglion cell types in the retina of the marmoset monkey (Callithrix jacchus). Ganglion cells were transfected via particle-mediated gene transfer of an expression plasmid for the postsynaptic density 95-green fluorescent protein (PSD95-GFP), and DB3a cells were labeled via immunohistochemistry. Ganglion cell types that fully or partially costratified with DB3a cells included OFF parasol, OFF midget, broad thorny, recursive bistratified, small bistratified, and large bistratified cells. On average, the number of DB3a contacts to parasol cells (18 contacts per axon terminal) is higher than that to other ganglion cell types (between four and seven contacts). We estimate that the DB3a output to OFF parasol cells accounts for at least 30% of the total DB3a output. Furthermore, we found that OFF parasol cells receive approximately 20% of their total bipolar input from DB3a cells, suggesting that other diffuse bipolar types also provide input to OFF parasol cells. We conclude that DB3a cells preferentially contact OFF parasol cells but also provide input to other ganglion cell types. PMID- 26559917 TI - Early repolarization pattern and its day-to-day dynamic change as markers for ventricular fibrillation in patients with vasospastic angina. AB - AIMS: An early repolarization (ER) pattern is a risk factor for ventricular fibrillation (VF) in certain diseases. However, it is unclear whether this association holds for patients with vasospastic angina (VSA). Moreover, the reported long-term follow-up of implantable cardioverter defibrillator (ICD) therapy for VSA patients is limited to 3 years. This study aimed to clarify the relation between ER and VF in patients with VSA and to investigate the long-term outcomes of ICD therapy. METHODS AND RESULTS: This retrospective, observational survey evaluated 265 consecutive VSA patients, including 21 with VF. Their electrocardiogram findings and clinical course were analysed over a mean follow up of 5.5 +/- 3.3 years. Early repolarization was observed in 64 patients (24.2%) and was more frequent in patients with VF history than those without (P = 0.001). Early repolarization was independently associated with VF history. During follow up, four patients had VF recurrences. Ventricular fibrillation recurrence was higher in patients with ER (log-rank, P = 0.018) or VF history (log-rank, P < 0.001) than those without. Among patients with ER, day-to-day variations in ER (P = 0.003) and notching of ER pattern (P = 0.03) were associated with VF history. Cases with day-to-day variation showed a higher incidence of VF recurrence during follow-up (log-rank, P = 0.007). During long-term follow-up, 23.5% of patients with an ICD received appropriate shock therapy. CONCLUSION: The presence of ER, especially with day-to-day variation, can help predict VF recurrence in VSA patients. Implantable cardioverter defibrillator implantation is a reasonable approach for the secondary prevention of VF in high-risk VSA patients. PMID- 26559916 TI - Near zerO fluoroscopic exPosure during catheter ablAtion of supRavenTricular arrhYthmias: the NO-PARTY multicentre randomized trial. AB - AIMS: Aim of this study was to compare a minimally fluoroscopic radiofrequency catheter ablation with conventional fluoroscopy-guided ablation for supraventricular tachycardias (SVTs) in terms of ionizing radiation exposure for patient and operator and to estimate patients' lifetime attributable risks associated with such exposure. METHODS AND RESULTS: We performed a prospective, multicentre, randomized controlled trial in six electrophysiology (EP) laboratories in Italy. A total of 262 patients undergoing EP studies for SVT were randomized to perform a minimally fluoroscopic approach (MFA) procedure with the EnSiteTMNavXTM navigation system or a conventional approach (ConvA) procedure. The MFA was associated with a significant reduction in patients' radiation dose (0 mSv, iqr 0-0.08 vs. 8.87 mSv, iqr 3.67-22.01; P < 0.00001), total fluoroscopy time (0 s, iqr 0-12 vs. 859 s, iqr 545-1346; P < 0.00001), and operator radiation dose (1.55 vs. 25.33 uS per procedure; P < 0.001). In the MFA group, X-ray was not used at all in 72% (96/134) of cases. The acute success and complication rates were not different between the two groups (P = ns). The reduction in patients' exposure shows a 96% reduction in the estimated risks of cancer incidence and mortality and an important reduction in estimated years of life lost and years of life affected. Based on economic considerations, the benefits of MFA for patients and professionals are likely to justify its additional costs. CONCLUSION: This is the first multicentre randomized trial showing that a MFA in the ablation of SVTs dramatically reduces patients' exposure, risks of cancer incidence and mortality, and years of life affected and lost, keeping safety and efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01132274. PMID- 26559918 TI - Cavotricuspid isthmus ablation using a catheter equipped with mini electrodes on the 8 mm tip: a prospective comparison with an 8 mm dumbbell-shaped tip catheter and 8 mm tip cryothermal catheter. AB - AIMS: The mini electrodes (ME) placed on the tip of the ablation electrode provide more precise local signal. We evaluated whether ME catheter was effective for the ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter. METHODS AND RESULTS: Eighty-five consecutive patients (68 men; 62 +/- 10 years) underwent CTI ablation either using a catheter equipped with ME on the 8 mm tip (ME catheter) in 25 patients (Group A), 8 mm dumbbell-shaped (DS) tip catheter (DS catheter) in 30 patients (Group B), or 8 mm tip cryothermal catheter (Cryo catheter) in 30 patients (Group C). In cases of failed isthmus block, the catheter was changed to the other catheter, but patients remained in the original group following intention-to-treat analysis. The endpoint was achieved in all patients after 13 +/- 7 applications in Group A, 9 +/- 4 applications in Group B, and 5 +/- 2 applications in Group C (P < 0.001). The fluoroscopic and procedure times were significantly longer in Group A (9 +/- 7 and 28 +/- 17 min, P = 0.001, and P = 0.002, respectively) when compared with Groups B (6 +/- 4 and 13 +/- 6 min) and C (4 +/- 3 and 14 +/- 7 min). A crossover was performed in 14 (56%) Group A patients, and 3 (10%) Group C patients. The mean power delivered in Group A was significantly lower than in Group B (31.3 +/- 9.1 vs. 38.6 +/- 7.6 W, P = 0.015). CONCLUSION: The ME catheter was found to be less effective than the Cryo catheter and a DS catheter for the CTI ablation. PMID- 26559919 TI - Familial clustering and subsequent incidence of atrial fibrillation among first degree relatives in Denmark. AB - AIMS: Atrial fibrillation (AF) is associated with increased morbidity and mortality. Determination and quantification of familial risk may help identify high-risk patients. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2012), we identified all first-time AF patients (probands) in Denmark. Relatives to these probands were grouped according to proband-relation: offspring from either maternal or paternal proband, and siblings to proband. Age-specific incidence of AF for these three groups of relatives and for the general Danish population was estimated. Using the general population as reference, we calculated adjusted rate ratios (RRs) of AF in the three groups of relatives. We identified 67 310, 103 822, and 11 800 AF probands who were mothers (median age 74 years, IQR 66-81), fathers (70 years, IQR 62-78), and siblings (46 years, IQR 38-52), respectively. Among those, 133 516, 221 774, and 21 448 offspring from a maternal proband, offspring from a paternal proband, and siblings, respectively, were screened for incident AF. This was recorded in 2536 (1.9%), 2906 (1.3%), and 292 (1.4%) relatives, respectively. Compared with the general Danish population, the adjusted RRs for incident AF were 3.37 [95% confidence interval (CI) 3.21 3.53] for offspring from maternal probands, 2.81 (95% CI 2.69-2.93) for offspring from paternal probands, and 5.20 (95% CI 4.61-5.85) for siblings to sibling probands. Subgroup analyses showed increased RRs with younger aged probands. CONCLUSION: Familial AF was associated with an increased RR of AF in first-degree relatives compared with the general Danish population. This suggests that familial AF is a major risk factor for developing AF in relatives. PMID- 26559920 TI - Pacemakers implantation and radiofrequency catheter ablation procedures during medical missions in Morocco: an 8-year experience. AB - AIMS: Radiofrequency catheter ablation (RFCA) for arrhythmias in the context of short-term medical missions (MM) in a developing country has not been reported so far. We describe here our experience with RFCA and pacemaker implantation in Morocco with a fully portable electrophysiological (EP) system under the auspice of the Monaco-Morocco Cardiology Association. METHODS AND RESULTS: Since November 2007, two to three MM (mean duration 4 days including transportation) per year were conducted (including two physicians and one nurse from Monaco) and were alternately located in Marrakech, Fes, Agadir, Casablanca, Rabat, Essaouira, and Oujda. All patients' files were sent by local teams and/or referring Moroccan cardiologists before MM. Each case was discussed with the Monaco EP team before the MM. Pacemakers and leads were donated by companies (Sorin Group, Medtronic, Saint-Jude Medical). The EP system (EP Tracer, CardioTek) as well as diagnostic/ablation catheters were brought for RFCA procedures. After the procedures, follow-up was performed by local teams. Procedures took place in gynaecological or orthopaedic operating room, or, when available, in the interventional cardiology cathlab. Thirty-one RFCA were performed during 11 MM (atrioventricular node re-entrant tachycardia = 12; atrioventricular re-entrant tachycardia/Mahaim fibre = 15; typical atrial flutter = 3; ventricular ectopy = 1). Acute success was 93.5% for RFCA. Two major RFCA-related complications occurred (air embolism and complete atrioventricular block). No complication was related to pacemaker implantations (n = 44; mean 4 pacemakers per mission). CONCLUSION: Radiofrequency catheter ablation for arrhythmias in developing countries is technically challenging but feasible, despite technical and cultural difficulties. PMID- 26559921 TI - Deficiencies in the health care system contribute to a high rate of late HIV diagnosis in Sweden. AB - OBJECTIVES: The aim of the study was to identify factors in HIV-infected patients and the health care system which contribute to late diagnosis. METHODS: All patients who were newly diagnosed with HIV infection at 12 clinics in Sweden over a period of 2.5 years (n = 575) were included in the study, corresponding to three-quarters of newly diagnosed HIV infections in the country. The patients were classified as non-late presenters or late presenters (LPs), defined as those with a CD4 count < 350 cells/MUL or AIDS. LPs were subdivided into those without and those with advanced HIV disease, which was defined as a CD4 count < 200 cells/MUL or AIDS. Demographics, missed AIDS and HIV-associated symptoms in the preceding 3 years, immigration date, and health examination at immigration were recorded. RESULTS: Fifty-eight per cent of the patients were LPs, of whom 66% had advanced disease. Age > 30 years, origin in sub-Saharan Africa or Eastern Europe/Asia/the Pacific region, and country of transmission being in sub-Saharan Africa or unknown were associated with late presentation. Half of the patients of non-Swedish origin had lived for more than 1 year in Sweden at diagnosis and 66% had a missed HIV testing opportunity at immigration. Twenty-seven per cent of all patients had presented for health care with AIDS- and/or HIV-associated conditions without having an HIV test. Sixteen per cent had a history of symptoms without seeking care. CONCLUSIONS: Deficiencies in the health care system with missed HIV testing opportunities contribute to the high proportion of late presenters in Sweden, especially among migrants. With increased testing at immigration and further incorporation of "indicator-guided" testing in general practice, most patients could be diagnosed earlier. PMID- 26559922 TI - TB/HIV co-infections and associated factors among patients on directly observed treatment short course in Northeastern Ethiopia: a 4 years retrospective study. AB - BACKGROUND: Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading independent global causes of death among patients with infectious diseases. Additionally, due to the shared immune defense mechanisms, they are the leading cause of co-morbidities globally. However, little information was found regarding the proportion of TB/HIV co-infection in the study area. Thus, this study determined the proportion and associated factors of TB/HIV co-infection. METHODS: All TB patients treated from January/2011 to December/2014 were included in this study. Data were collected from three health centers namely; Kobo, Robit and Gobiye. Data were entered, cleared, and analyzed using SPSS version 20. Frequency, percentage, median and range were used to present the data. To assess the associated factors, logistic regression was employed. RESULTS: Of the total 990 TB patients enrolled in the study, 98.2 % were screened for HIV; of these, 24.3 % were co-infected with TB and HIV. The odds of having TB/HIV co-infection were 3.4 times higher among in the age group of 25-45 years compared to older (>=45 years) age TB patients (OR = 3.4; 95 % CI 2-5). Moreover, the odds of having TB/HIV co-infection were 2.8 and 1.7 times higher among smear positive and smear negative patients with pulmonary TB respectively than patients with extra pulmonary TB. Of 236 co-infected patients, 71.2 % took co-trimoxazole preventive therapy and 76.3 % took antiretroviral treatment. CONCLUSION: TB/HIV co-infection is one of the serious public health problems in the study area. Thus, Collaborative TB/HIV activities that reduce the co-morbidities and mortalities should be addressed. PMID- 26559923 TI - Pushing Single-Oxygen-Atom-Bridged Bimetallic Systems to the Right: A Cryptand Encapsulated Co-O-Co Unit. AB - A dicobalt(II) complex, [Co2(mBDCA-5t)](2-) (1), demonstrates a cofacial arrangement of trigonal monopyramidal Co(II) ions with an inter-metal separation of 6.2710(6) A. Reaction of 1 with potassium superoxide generates an encapsulated Co-O-Co core in the dianionic complex, [Co2O(mBDCA-5t)](2-) (2); to form the linear Co-O-Co core, the inter-metal distance has diminished to 3.994(3) A. Co K edge X-ray absorption spectroscopy data are consistent with a +2 oxidation state assignment for Co in both 1 and 2. Multireference complete active space calculations followed by second-order perturbation theory support this assignment, with hole equivalents residing on the bridging O-atom and on the cryptand ligand for the case of 2. Complex 2 acts as a 2-e(-) oxidant toward substrates including CO and H2, in both cases efficiently regenerating 1 in what represent net oxygen-atom-transfer reactions. This dicobalt system also functions as a catalase upon treatment with H2O2. PMID- 26559924 TI - Description of Luteimonas pelagia sp. nov., isolated from marine sediment, and emended descriptions of Luteimonas aquatica, Luteimonas composti, Luteimonas mephitis, Lysobacter enzymogenes and Lysobacter panaciterrae. AB - An aerobic, Gram-stain-negative, non-motile, rod-shaped bacterium, designated strain CC-VAM-7T, was isolated from a marine sediment sample collected at Kending, Taiwan. The isolate grew optimally at pH 7.0 and 30 degrees C and in the presence of 4 % (w/v) NaCl. The most closely related strains in terms of 16S rRNA gene sequence similarity were the type strains of Luteimonas huabeiensis (95.2 %) and Lysobacter defluvii (95.0 %). Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain CC-VAM-7T clustered with members of the genus Luteimonas. Strain CC-VAM-7T possessed C15 : 1omega5c, C16 : 1omega5c, iso C11 : 0, iso-C15 : 0, iso-C16 : 0, iso-C17 : 0, iso-C11 : 0 3-OH and summed feature 9 (10-methyl C16 : 0 and/or iso-C17 : 1omega9c) as predominant fatty acids. The polar lipid profile contained major amounts of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine and moderate amounts of an unidentified phospholipid. The genomic DNA G+C content was 73.4 mol%. Ubiquinone 8 (Q-8) was the predominant respiratory quinone. According to its distinct phylogenetic, phenotypic and chemotaxonomic features, which were in line with those of other members of the genus Luteimonas, strain CC-VAM-7T is proposed to represent a novel species within the genus Luteimonas, for which the name Luteimonas pelagia sp. nov. is proposed. The type strain is CC-VAM-7T ( = BCRC 80558T = JCM 18792T). In addition, we propose emended descriptions of Luteimonas aquaticaChou et al. 2008, Luteimonas compostiYoung et al. 2007, Luteimonas mephitisFinkmann et al. 2000, Lysobacter enzymogenesChristensen and Cook 1978 and Lysobacter panaciterraeTen et al. 2009. PMID- 26559925 TI - Protein aggregation as an antibiotic design strategy. AB - Taking advantage of the xenobiotic nature of bacterial infections, we tested whether the cytotoxicity of protein aggregation can be targeted to bacterial pathogens without affecting their mammalian hosts. In particular, we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased in vitro screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin-resistant Staphylococcus aureus. Upon parenteral administration in vivo, the peptides cured mice from bacterial sepsis without apparent toxic side effects as judged from histological and hematological evaluation. We found that the peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation-prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases. PMID- 26559927 TI - Use of Smart Technology for Remote Consultation in the Pediatric Cardiac Catheterization Laboratory. AB - OBJECTIVES: To evaluate the use of smartphone and tablet technology ("smart technology" or ST) in remote consultation for pediatric and congenital cardiac catheterization. DESIGN: Two online surveys, to early-career (Mentees) and senior (Mentors) pediatric interventional cardiologists, designed to assess the current use and attitudes toward ST for remote consultation. In addition, the current literature is reviewed for use of remote consultations and potential legal and patient privacy concerns. RESULTS: Forty-six (40%) Mentees and 19 (48%) Mentors responded. 74% of Mentees report using ST for remote consultation, 26% for nearly every case, with 45% of communication occurring during a procedure. Over one third of Mentees report they have performed an intervention for the first time based on ST consultation. Of Mentors that reported receiving ST consultation, 58% were comfortable providing advice via this method, but 42% felt that the imaging sent was inadequate to provide appropriate advice for at least one case. Both groups felt the speed of consultation was much faster using ST. Privacy measures were reportedly used in up to 85% of consultations, while only 12% of respondents obtained informed consent for the consultation. The most common barrier identified by Mentees for use of ST for consultations was patient privacy concerns. CONCLUSIONS: ST use is prevalent among early-career pediatric and congenital interventional cardiologists for consultation regarding catheterization procedures. There are many technologic, legal, and patient privacy concerns that will need to be addressed as the use of ST for remote consultation grows. PMID- 26559926 TI - Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms. AB - Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID- 26559928 TI - Knowledge translation regarding financial abuse and dementia for the banking sector: the development and testing of an education tool. AB - OBJECTIVE: Financial abuse is the most common form of elder abuse. Capacity Australia, established to promote education regarding capacity and abuse prevention across health, legal and financial sectors, was awarded a grant by the Dementia Collaborative Research Centre to educate the banking sector on financial abuse and dementia. We aimed to develop a knowledge translation tool for bank staff on this issue. METHODS: The banking sector across Australia was engaged and consulted to develop a tailored education tool based on Australian Banking Association's Guidelines on Financial Abuse Prevention, supplemented by information related to dementia, financial capacity and supported decision making. The tool was tested on 69 banking staff across Australia from two major banks. RESULTS: An online education tool using adaptive learning was developed, comprising a pretest of 15 multiple choice questions, followed by a learning module tailored to the individual's performance on the pretest, and a post-test to assess knowledge translation. A significant increase in scores was demonstrated when baseline scores were compared with post-course scores (mean difference in scores = 3.5; SD = 1.94; t = 15.1; df = 68; p < 0.001). The tool took approximately 10-20 min to complete depending on the knowledge of participant and continuity of completion. CONCLUSIONS: The Australian banking industry was amenable to assist in the development of a tailored education tool on dementia, abuse and financial capacity. This online e-tool provides an effective medium for knowledge translation. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26559929 TI - Impact of antibiotic choices made in the emergency department on appropriateness of antibiotic treatment of urinary tract infections in hospitalized patients. AB - BACKGROUND: Overuse of antibiotics to treat urinary tract infections (UTIs) is common in hospitalized patients and may begin in the emergency department (ED). METHODS: For a 4-week period we reviewed medical records of all patients admitted to the hospital who initiated treatment for a UTI in the ED. RESULTS: According to study criteria, initiation of antibiotics was inappropriate for 55 of 94 patients (59% [95% confidence interval {CI}, 48%-69%]), and continuation after admission was inappropriate for 54 of 80 patients (68% [95% CI, 57%-78%]). CONCLUSION: Failure to reevaluate the need for antibiotics initiated in the ED to treat UTIs may lead to overuse of antibiotics in hospitalized patients. PMID- 26559930 TI - Clinical implications of and lessons learnt from external assessment of Mers-CoV diagnostics. AB - With the emergence of new viral infections, it is necessary to set up new target specific assays, based on existing molecular techniques such as real-time PCR, as quickly as possible. Without these diagnostic tools, the geographical spread of new infections, follow-up of the disease outbreak and analysis of the pathogenesis of the disease are not possible. Therefore, the genomic information of the emerging pathogen, diagnostic protocols and standards allowing quality control need to be available in a few days. This can only be implemented with good quality experienced laboratories having suitable infrastructure to establish in-house assays. Even though these molecular tools are available quickly, challenges still remain with what sample types to select for a proper diagnostic value. PMID- 26559931 TI - Selective enhancement of individual cantilever high resonance modes. AB - Multifrequency atomic force microscopy (AFM) in liquid media where several eigenmodes or harmonics are simultaneously excited is improving the performance of the scanning probe techniques in biological studies. As a consequence, an important effort is being made to search for a reliable, efficient and strong cantilever high mode excitation method that operates in liquids. In this work we present (theoretical and experimentally) a technique for improving the efficiency of the most common excitation methods currently used in AFM operated in liquids: photothermal, torque (MAC ModeTM) and magnetostriction. By etching specific areas of the cantilever coating, the oscillation amplitude (both flexural and torsional) of each specific eigenmode increases, leading to an improvement in signal to noise ratio of the multifrequency techniques. As an alternative, increment in high mode oscillation amplitude is also obtained by Ga(+) ion implantation in the specific areas of the magnetic material. PMID- 26559932 TI - sigma Aromaticity Dominates in the Unsaturated Three-Membered Ring of Cyclopropametallapentalenes from Groups 7-9: A DFT Study. AB - Aromaticity, an old but still fantastic topic, has long attracted considerable interest of chemists. Generally, pi aromaticity is described by pi-electron delocalization in closed circuits of unsaturated compounds whereas sigma-electron delocalization in saturated rings leads to sigma aromaticity. Interestingly, our recent study shows that sigma aromaticity can be dominating in an unsaturated three-membered ring (3MR) of cyclopropaosmapentalene. An interesting question is raised: Can the sigma aromaticity, which is dominant in the unsaturated 3MR, be extended to other cyclopropametallapentalenes? If so, how could the metal centers, ligands, and substituents affect the sigma aromaticity? Here, we report a thorough theoretical study on these issues. The nucleus-independent chemical shift calculations and the anisotropy of the current-induced density plots reveal the dominant sigma aromaticity in these unsaturated 3MRs. In addition, our calculations show that substituents on the 3MRs have significant effects on the sigma aromaticity, whereas the ligand effect is particularly small. PMID- 26559933 TI - Epithelial downgrowth after cataract surgery: an atypical presentation with scleral thinning and massive seeding in anterior chamber. AB - PURPOSE: To report an atypical presentation of epithelial downgrowth (ED) after clear cornea cataract extraction, characterized by mixed clinical expression of both cystic and diffuse form and massive epithelial debris seeding in anterior chamber, associated with scleral involvement. METHODS: In this case report, fine needle anterior chamber aspiration cytology was performed to identify pathologic tissue invading iris, cornea, and angular structures. The patient was treated with anterior chamber membrane surgical excision. RESULTS: Epithelial downgrowth was identified by cytologic assessment. The patient was treated with epithelial membrane peeling and scleral defect conjunctival covering. This conservative surgical approach led to a significant reduction of ocular pain. During follow up, residual epithelial tissue was present in anterior chamber without tendency to regrowth. CONCLUSIONS: In doubtful cases of ED, histocytopathologic analysis should be performed without hesitation. Avoiding more invasive procedures, early detection and prompt surgical approach can result in improved outcome even in case of extensive intraocular involvement. PMID- 26559934 TI - Errors in IOL power study methodology. PMID- 26559935 TI - Choroidal effusion and suprachoroidal hemorrhage during phacoemulsification: intraoperative management to prevent expulsive hemorrhage. AB - PURPOSE: To describe the intraoperative management of choroidal effusion (CE) or suprachoroidal hemorrhage (SCH) during cataract surgery with the phacoemulsification technique. METHODS: The study is a retrospective interventional study through which we describe the intraoperative management adopted in 6 cases of CE or SCH during cataract surgery. The study involved 6,400 eyes (phacoemulsification) in 6 years observational time (incidence rate 0.094%). The surgical time at which these complications happened differed: nucleolus phacoemulsification in 2 eyes, cortex removal by bimanual irrigation-aspiration in 3 eyes, and intraocular lens implant for 1 eye. Once the complication was recognized, each patient was quickly moved to an extreme reverse Trendelenburg position and pharmacologically treated to manage high blood pressure, pain, and anxiety (150 mL of an 18% mannitol solution delivered in rapid infusion intravenously; 1-3 mg intravenous midazolam; 5 nifedipine sublingual drops). RESULTS: In all the cases reported, the surgery was completed after resolution of the acute choroidal exudation or SCH. In the follow-up evaluation, the intraocular pressure was normal at each examination. The visual acuity of the patients was between 6/7.5 and 5/6 Snellen after 4 weeks. We observed a statistically significant reduction in endothelial cells in the 2 eyes in which the CE or SCH happened during the phacoemulsification compared with the other cases; this finding likely results from mechanical damage (p = 0.04 [95% confidence interval]). CONCLUSIONS: Choroidal effusion or SCH can be intraoperatively managed to avoid expulsive hemorrhage and maintain the possibility of completing the surgery. PMID- 26559936 TI - Preoperative platelet transfusions and perioperative red blood cell requirements in patients with thrombocytopenia undergoing noncardiac surgery. AB - BACKGROUND: Perioperative hemorrhage impacts patient outcomes and health care resource utilization, yet the risks of transfusion therapies are significant. In patients with preoperative thrombocytopenia, the effects of prophylactic preoperative platelet (PLT) transfusion on perioperative bleeding complications remain uncertain. STUDY DESIGN AND METHODS: This is a retrospective cohort study of noncardiac surgical patients between January 1, 2008, and December 31, 2011. Propensity-adjusted analyses were used to evaluate associations between preoperative thrombocytopenia, preoperative PLT transfusion, and the outcomes of interest, with a primary outcome of perioperative red blood cell (RBC) transfusion. RESULTS: A total of 13,978 study participants were included; 860 (6.2%) had a PLT count of not more than 100 * 10(9) /L with 71 (8.3%) receiving PLTs preoperatively. Administration of PLTs was associated with higher rates of perioperative RBC transfusion (66.2% vs. 49.1%, p = 0.0065); however, in propensity-adjusted analysis there was no significant difference between groups (odds ratio [OR] [95% confidence interval {95% CI}], 1.68 [0.95-2.99]; p = 0.0764]. Patients receiving PLTs had higher rates of intensive care unit (ICU) admission (OR [95% CI], 1.95 [1.10-3.46]; p = 0.0224) and longer hospital lengths of stay (estimate [95% bootstrap CI], 7.2 [0.8-13.9] days; p = 0.0006) in propensity-adjusted analyses. CONCLUSION: Preoperative PLT transfusion did not attenuate RBC requirements in patients with thrombocytopenia undergoing noncardiac surgery. Moreover, preoperative PLT transfusion was associated with increased ICU admission rates and hospital duration. These findings suggest that more conservative management of preoperative thrombocytopenia may be warranted. PMID- 26559937 TI - Sexual dysfunction related to antiepileptic drugs in patients with epilepsy. AB - INTRODUCTION: Epilepsy is a common disease that is mostly treated with antiepileptic drugs (AEDs). However, the sexual dysfunction (SD) side effects related to the use of AEDs have not received sufficient attention. AREAS COVERED: The purpose of this review is to examine the current evidence on SD-related side effects of AEDs. The incidence, clinical features and major types of SD are summarized. Furthermore, various AEDs that may cause SDs are addressed in detail. Finally, we briefly summarize the treatments for SD related to AEDs. EXPERT OPINION: SD related to AEDs is common. Symptoms include erectile dysfunction (ED), hyposexuality, hypersexuality and ejaculatory dysfunction. Traditional AEDs such as valproate and enzyme-inducing AEDs (EIAEDs) may produce high incidences of decreased libido. Recently, sexual function changes related to new AEDs have been reported. Topiramate, pregabalin and gabapentin may cause SD, whereas oxcarbazepine, lamotrigine and levetiracetam may improve sexual function. Although the treatment for SD related to AEDs remains unclear, switching to another AED may be an option. Further studies are necessary to better understand and treat SD related to AEDs. PMID- 26559938 TI - Phthalates Exert Multiple Effects on Leydig Cell Steroidogenesis. AB - Humans are significantly exposed to phthalates via food packaging, cosmetics and medical devices such as tubings and catheters. Testicular Leydig cells (LCs) are suggested to be among the main targets of phthalate toxicity in the body. However, their sensitivity to phthalates is species-dependent. This paper describes the response of the LCs from different species (mouse, rat and human) to phthalate exposure in different experimental paradigms (in vivo, ex vivo and in vitro), with particular focus on mechanisms of phthalate action on LC steroidogenesis. A comprehensive analysis of the impact of phthalate diesters and phthalate monoesters on LCs in different stages of their development is presented and possible mechanisms of phthalates action are discussed. Finally novel, not yet fully elucidated sites of action of phthalate monoesters on the backdoor pathway of 5alpha-dihydrotestosterone biosynthesis in immature mouse LCs and their effects on steroidogenesis and redox state in adult mouse LCs are reported. PMID- 26559939 TI - The structural HCV genes delivered by MPG cell penetrating peptide are directed to enhance immune responses in mice model. AB - One of the significant problems in vaccination projects is the lack of an effective vaccine against hepatitis C virus (HCV). The goal of the current study is to evaluate and compare two DNA constructs encoding HCV core and coreE1E2 genes alone or complexed with MPG peptide as a delivery system for stimulation of antibody responses and IFN-gamma secretion in Balb/c mice model. Indeed, MPG cell penetrating peptide was used to improve DNA immunization in mice. Our results demonstrated that MPG forms stable non-covalent nanoparticles with pcDNA-core and pcDNA-coreE1E2 at an N/P ratio of 10:1. The in vitro transfection efficiency of core or coreE1E2 DNA using MPG and TurboFect delivery systems was confirmed by western blot analysis. The results indicated the expression of the full-length core (~21 kDa), and coreE1E2 (~83 kDa) proteins using an anti-His monoclonal antibody. In addition, the expression of HCV core and coreE1E2 proteins was performed in bacteria and the purified recombinant proteins were injected to mice with Montanide 720 adjuvant. Our data showed that the immunized mice with HCV core and coreE1E2 proteins generated the mixture of sera IgG1 and IgG2a isotypes considerably higher than other groups. Furthermore, DNA constructs encoding core and coreE1E2 complexed with MPG could significantly induce IFN-gamma secretion in lower concentrations than the naked core and coreE1E2 DNAs. Taken together, the DNA formulations as well as protein regimens used in this study triggered high level IFN-gamma production in mice, an important feature for the development of Th1 immune responses. PMID- 26559940 TI - Genome-wide mapping of Hif-1alpha binding sites in zebrafish. AB - BACKGROUND: Hypoxia Inducible Factor (HIF) regulates a cascade of transcriptional events in response to decreased oxygenation, acting from the cellular to the physiological level. This response is evolutionarily conserved, allowing the use of zebrafish (Danio rerio) as a model for studying the hypoxic response. Activation of the hypoxic response can be achieved in zebrafish by homozygous null mutation of the von Hippel-Lindau (vhl) tumour suppressor gene. Previous work from our lab has focused on the phenotypic characterisation of this mutant, establishing the links between vhl mutation, the hypoxic response and cancer. To further develop fish as a model for studying hypoxic signalling, we examine the transcriptional profile of the vhl mutant with respect to Hif-1alpha. As our approach uses embryos consisting of many cell types, it has the potential to uncover additional HIF regulated genes that have escaped detection in analogous mammalian cell culture studies. RESULTS: We performed high-density oligonucleotide microarray analysis of the gene expression changes in von Hippel Lindau mutant zebrafish, which identified up-regulation of well-known hypoxia response genes and down-regulation of genes primarily involved in lipid processing. To identify the dependency of these transcriptional changes on HIF, we undertook Chromatin Immunoprecipitation linked next generation sequencing (ChIP-seq) for the transcription factor Hypoxia Inducible Factor 1alpha (HIF 1alpha). We identified HIF-1alpha binding sites across the genome, with binding sites showing enrichment for an RCGTG motif, showing conservation with the mammalian hypoxia response element. CONCLUSIONS: Transcriptome analysis of vhl mutant embryos detected activation of key hypoxia response genes seen in human cell models of hypoxia, but also suppression of many genes primarily involved in lipid processing. ChIP-seq analysis of Hif-1alpha binding sites unveiled an unprecedented number of loci, with a high proportion containing a canonical hypoxia response element. Whether these sites are functional remains unknown, nevertheless their frequent location near transcriptional start sites suggests functionality, and will allow for investigation into the potential hypoxic regulation of genes in their vicinity. We expect that our data will be an excellent starting point for analysis of both fish and mammalian gene regulation by HIF. PMID- 26559942 TI - Pharmacotherapeutic options for hepatitis B. AB - INTRODUCTION: Hepatitis B virus (HBV) is the driving force of disease progression in chronic hepatitis B. Patients with active HBV replication and/or significant liver disease require timely treatment. Currently, pegylated interferon-alpha (PEG IFN), entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the preferred first-line drugs. AREAS COVERED: A finite course IFN-based therapy has modest response and may reduce cirrhosis or hepatocellular carcinoma development. Nucleos(t)ide analogs (Nuc) have excellent safety profile, cumulative or maintained response and long-term efficacy in terms of reduction or reversal of fibrosis, decrease in development of cirrhosis and its adverse sequalae. The optimal duration of Nuc therapy is unknown and a feasible stopping rule with off therapy monitoring plan has been developed. EXPERT OPINION: Choosing a drug to initiate therapy in a right patient at a right time should be primarily based on the prospect and likelihood for improved outcomes. Nuc is the only choice for patients with hepatic decompensation, pregnant women and those about to receive immune/chemotherapy or organ transplantation. IFN-based therapy is preferred in patients with compensated liver disease, particularly in young patients, females of childbearing age. The development of new drugs and new strategies is the highest priority in further improving the outcomes of treatment. PMID- 26559941 TI - On Heels and Toes: How Ants Climb with Adhesive Pads and Tarsal Friction Hair Arrays. AB - Ants are able to climb effortlessly on vertical and inverted smooth surfaces. When climbing, their feet touch the substrate not only with their pretarsal adhesive pads but also with dense arrays of fine hairs on the ventral side of the 3rd and 4th tarsal segments. To understand what role these different attachment structures play during locomotion, we analysed leg kinematics and recorded single leg ground reaction forces in Weaver ants (Oecophylla smaragdina) climbing vertically on a smooth glass substrate. We found that the ants engaged different attachment structures depending on whether their feet were above or below their Centre of Mass (CoM). Legs above the CoM pulled and engaged the arolia ('toes'), whereas legs below the CoM pushed with the 3rd and 4th tarsomeres ('heels') in surface contact. Legs above the CoM carried a significantly larger proportion of the body weight than legs below the CoM. Force measurements on individual ant tarsi showed that friction increased with normal load as a result of the bending and increasing side contact of the tarsal hairs. On a rough sandpaper substrate, the tarsal hairs generated higher friction forces in the pushing than in the pulling direction, whereas the reverse effect was found on the smooth substrate. When the tarsal hairs were pushed, buckling was observed for forces exceeding the shear forces found in climbing ants. Adhesion forces were small but not negligible, and higher on the smooth substrate. Our results indicate that the dense tarsal hair arrays produce friction forces when pressed against the substrate, and help the ants to push outwards during horizontal and vertical walking. PMID- 26559943 TI - Influence of body mass index on revision rates after primary total knee arthroplasty. AB - PURPOSE: Studies demonstrate that revision rates after primary total knee arthroplasty (TKA) tend to be higher in obese patients. However, the existence of a body mass index (BMI) threshold remains unexplored. METHODS: We conducted a prospective cohort study of 2442 primary TKAs in 2035 patients (69.1 % women; mean age 72 years; mean follow-up 93 months, range 38-203). We evaluated the influence of BMI in five categories on all-cause revision after TKA using incidence rates (IR), hazard ratios (HR), and Kaplan-Meier survival analysis. Adjustment for baseline imbalances was performed using Cox regression analysis. RESULTS: Over the study period, 71 revisions occurred. Revision rates were 3.2 cases/1000 patient-years for patients of normal weight, 3.4/1000 for overweight patients and 3.0/1000 for patients classified as obese class I. At BMI >= 35, a significant increase in revision was noted. Comparing BMI >= 35 vs. < 35, there were 6.4 vs. 3.2 /1000. Crude HR was 2.0 [95 % confidence interval (CI) 1.2-3.3, p = 0.009], and the adjusted HR was 2.1 (95 % CI 1.2-3.6, p = 0.008). CONCLUSION: All-cause revision rates after primary TKA doubled in patients with a BMI of 35 but were similar in those with a BMI <35. PMID- 26559944 TI - Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis. AB - BACKGROUND: The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks. OBJECTIVE: To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model. METHODS: Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments. RESULTS: Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001) between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS) score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). CONCLUSIONS: Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading. PMID- 26559945 TI - Temporal Course of 2014 Ebola Virus Disease (EVD) Outbreak in West Africa Elucidated through Morbidity and Mortality Data: A Tale of Three Countries. AB - The explosive outbreak of Ebola virus disease (EVD) in West Africa in 2014 appeared to have lessened in 2015, but potentially continues be a global public health threat. A simple mathematical model, the Richards model, is utilized to gauge the temporal variability in the spread of the Ebola virus disease (EVD) in West Africa in terms of its reproduction number R and its temporal changes via detection of epidemic waves and turning points during the 2014 outbreaks in the three most severely affected countries; namely, Guinea, Liberia, and Sierra Leone. The results reveal multiple waves of infection in each of these three countries, of varying lengths from a little more than one week to more than one month. All three countries exhibit marginally fluctuating reproduction numbers during June-October before gradually declining. Although high mobility continues between neighboring populations of these countries across the borders, outbreak in these three countries exhibits decidedly different temporal patterns. Guinea had the most waves but maintained consistently low transmissibility and hence has the smallest number of reported cases. Liberia had highest level of transmission before October, but has remained low since, with no detectable wave after the New Year. Sierra Leone has gradually declining waves since October, but still generated detectable waves up to mid-March 2015, and hence has cumulated the largest number of cases-exceeding that of Guinea and Liberia combined. Analysis indicates that, despite massive amount of international relief and intervention efforts, the outbreak is persisting in these regions in waves, albeit more sparsely and at a much lower level since the beginning of 2015. PMID- 26559946 TI - Seasonal Dynamics in the Chemistry and Structure of the Fat Bodies of Bumblebee Queens. AB - Insects' fat bodies are responsible for nutrient storage and for a significant part of intermediary metabolism. Thus, it can be expected that the structure and content of the fat body will adaptively change, if an insect is going through different life stages. Bumblebee queens belong to such insects as they dramatically change their physiology several times over their lives in relation to their solitary overwintering, independent colony foundation stage, and during the colony life-cycle ending in the senescent stage. Here, we report on changes in the ultrastructure and lipid composition of the peripheral fat body of Bombus terrestris queens in relation to seasonal changes in the queens' activity. Six life stages are defined and evaluated in particular: pharate, callow, before and after hibernation, egg-laying, and senescence. Transmission electron microscopy revealed that the fat body contained two main cell types-adipocytes and oenocytes. Only adipocytes reveal important changes related to the life phase, and mostly the ration between inclusion and cytoplasm volume varies among particular stages. Both electron microscopy and chemical analyses of lipids highlighted seasonal variability in the quantity of the stored lipids, which peaked prior to hibernation. Triacylglycerols appeared to be the main energy source during hibernation, while the amount of glycogen before and after hibernation remained unchanged. In addition, we observed that the representation of some fatty acids within the triacylglycerols change during the queen's life. Last but not least, we show that fat body cell membranes do not undergo substantial changes concerning phospholipid composition in relation to overwintering. This finding supports the hypothesis that the cold-adaptation strategy of bumblebee queens is more likely to be based on polyol accumulation than on the restructuring of lipid membranes. PMID- 26559947 TI - To Share or Not to Share: Malaysian Healthcare Professionals' Views on Localized Prostate Cancer Treatment Decision Making Roles. AB - AIM: To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders' decision making roles in localized prostate cancer (PCa) treatment. METHODS: Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. FINDINGS: The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients' decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient's treatment due to Malaysia's close knit family culture. CONCLUSIONS: A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa. PMID- 26559948 TI - Psychosomatic consultation in the workplace: opportunities and limitations of the services offered--results of a qualitative study. AB - PURPOSE: In Germany, innovative concepts of anchoring psychotherapeutic consultations within an occupational setting emerge in models like the "psychosomatic consultation in the workplace" (PCIW). Characteristic quality is the close cooperation between company-based occupational health physicians (OPs) and external psychotherapeutic consultants. Little is currently known about the attitudes of OPs and other stakeholders in companies in terms of possible contributions of these offers to their tasks within the field of mental health and work. METHODS: Data were collected via individual interviews with different stakeholders (n = 8) and two OP focus groups (each n = 5) with and without experience with PCIW. Data were analysed with content analysis. RESULTS: Common mental disorders (CMD) were perceived as occurring increasingly but still being stigmatized. PCIW allows employees quick access to a neutral psychotherapist and thus might help to avoid chronification of CMD. For companies, this may mean that longer periods of absenteeism (and presenteeism) can be avoided. The interviewees also feel that the ongoing collaboration with a psychotherapeutic specialist may sensitize OPs to recognize mental disorders earlier and provide basic treatment. PCIW was stated as an early, easy and fast first access to psychotherapy. The effort of PCIW is limited if structural changes in the workplace are necessary to reduce mental stressors. Also, if financed by the company, PCIW should have clear time limits and cannot aim to replace health insurance benefits. CONCLUSIONS: Taking above-mentioned limitations into account, PCIW appears to be a promising tool to bridge the gap between OP-conducted company-based health promotion and early secondary care. PMID- 26559949 TI - Neural signatures for sustaining object representations attributed to others in preverbal human infants. AB - A major feat of social beings is to encode what their conspecifics see, know or believe. While various non-human animals show precursors of these abilities, humans perform uniquely sophisticated inferences about other people's mental states. However, it is still unclear how these possibly human-specific capacities develop and whether preverbal infants, similarly to adults, form representations of other agents' mental states, specifically metarepresentations. We explored the neurocognitive bases of eight-month-olds' ability to encode the world from another person's perspective, using gamma-band electroencephalographic activity over the temporal lobes, an established neural signature for sustained object representation after occlusion. We observed such gamma-band activity when an object was occluded from the infants' perspective, as well as when it was occluded only from the other person (study 1), and also when subsequently the object disappeared, but the person falsely believed the object to be present (study 2). These findings suggest that the cognitive systems involved in representing the world from infants' own perspective are also recruited for encoding others' beliefs. Such results point to an early-developing, powerful apparatus suitable to deal with multiple concurrent representations, and suggest that infants can have a metarepresentational understanding of other minds even before the onset of language. PMID- 26559950 TI - Epigenetic regulation of sex ratios may explain natural variation in self fertilization rates. AB - Self-fertilization (selfing) favours reproductive success when mate availability is low, but renders populations more vulnerable to environmental change by reducing genetic variability. A mixed-breeding strategy (alternating selfing and outcrossing) may allow species to balance these needs, but requires a system for regulating sexual identity. We explored the role of DNA methylation as a regulatory system for sex-ratio modulation in the mixed-mating fish Kryptolebias marmoratus. We found a significant interaction between sexual identity (male or hermaphrodite), temperature and methylation patterns when two selfing lines were exposed to different temperatures during development. We also identified several genes differentially methylated in males and hermaphrodites that represent candidates for the temperature-mediated sex regulation in K. marmoratus. We conclude that an epigenetic mechanism regulated by temperature modulates sexual identity in this selfing species, providing a potentially widespread mechanism by which environmental change may influence selfing rates. We also suggest that K. marmoratus, with naturally inbred populations, represents a good vertebrate model for epigenetic studies. PMID- 26559951 TI - Phenotypic divergence during speciation is inversely associated with differences in seasonal migration. AB - Differences in seasonal migration might promote reproductive isolation and differentiation by causing populations in migratory divides to arrive on the breeding grounds at different times and/or produce hybrids that take inferior migratory routes. We examined this question by quantifying divergence in song, colour, and morphology between sister pairs of North American migratory birds. We predicted that apparent rates of phenotypic differentiation would differ between pairs that do and do not form migratory divides. Consistent with this prediction, results from mixed effects models and Ornstein-Uhlenbeck models of evolution showed different rates of divergence between these groups; surprisingly, differentiation was greater among non-divide pairs. We interpret this finding as a result of variable rates of population blending and fusion between partially diverged forms. Ancient pairs of populations that subsequently fused are now observed as a single form, whereas those that did not fuse are observable as pairs and included in our study. We propose that fusion of two populations is more likely to occur when they have similar migratory routes and little other phenotypic differentiation that would cause reproductive isolation. By contrast, pairs with migratory divides are more likely to remain reproductively isolated, even when differing little in other phenotypic traits. These findings suggest that migratory differences may be one among several isolating barriers that prevent divergent populations from fusing and thereby increase the likelihood that they will continue differentiating as distinct species. PMID- 26559952 TI - Why does offspring size affect performance? Integrating metabolic scaling with life-history theory. AB - Within species, larger offspring typically outperform smaller offspring. While the relationship between offspring size and performance is ubiquitous, the cause of this relationship remains elusive. By linking metabolic and life-history theory, we provide a general explanation for why larger offspring perform better than smaller offspring. Using high-throughput respirometry arrays, we link metabolic rate to offspring size in two species of marine bryozoan. We found that metabolism scales allometrically with offspring size in both species: while larger offspring use absolutely more energy than smaller offspring, larger offspring use proportionally less of their maternally derived energy throughout the dependent, non-feeding phase. The increased metabolic efficiency of larger offspring while dependent on maternal investment may explain offspring size effects-larger offspring reach nutritional independence (feed for themselves) with a higher proportion of energy relative to structure than smaller offspring. These findings offer a potentially universal explanation for why larger offspring tend to perform better than smaller offspring but studies on other taxa are needed. PMID- 26559953 TI - A symbiont's dispersal strategy: condition-dependent dispersal underlies predictable variation in direct transmission among hosts. AB - Direct horizontal transmission of pathogenic and mutualistic symbionts has profound consequences for host and symbiont fitness alike. While the importance of contact rates for transmission is widely recognized, the processes that underlie variation in transmission during contact are rarely considered. Here, we took a symbiont's perspective of transmission as a form of dispersal and adopted the concept of condition-dependent dispersal strategies from the study of free living organisms to understand and predict variation in transmission in the cleaning symbiosis between crayfish and ectosymbiotic branchiobdellidan worms. Field study showed that symbiont reproductive success was correlated with host size and competition among worms for microhabitats. Laboratory experiments demonstrated high variability in transmission among host contacts. Moreover, symbionts were more likely to disperse when host size and competition for microhabitat created a fitness environment below a discrete minimum threshold. A predictive model based on a condition-dependent symbiont dispersal strategy correctly predicted transmission in 95% of experimental host encounters and the exact magnitude of transmission in 67%, both significantly better than predictions that assumed a fixed transmission rate. Our work provides a dispersal based understanding of symbiont transmission and suggests adaptive symbiont dispersal strategies can explain variation in transmission dynamics and complex patterns of host infection. PMID- 26559954 TI - How predation shaped fish: the impact of fin spines on body form evolution across teleosts. AB - It is well known that predators can induce morphological changes in some fish: individuals exposed to predation cues increase body depth and the length of spines. We hypothesize that these structures may evolve synergistically, as together, these traits will further enlarge the body dimensions of the fish that gape-limited predators must overcome. We therefore expect that the orientation of the spines will predict which body dimension increases in the presence of predators. Using phylogenetic comparative methods, we tested this prediction on the macroevolutionary scale across 347 teleost families, which display considerable variation in fin spines, body depth and width. Consistent with our predictions, we demonstrate that fin spines on the vertical plane (dorsal and anal fins) are associated with a deeper-bodied optimum. Lineages with spines on the horizontal plane (pectoral fins) are associated with a wider-bodied optimum. Optimal body dimensions across lineages without spines paralleling the body dimension match the allometric expectation. Additionally, lineages with longer spines have deeper and wider body dimensions. This evolutionary relationship between fin spines and body dimensions across teleosts reveals functional synergy between these two traits and a potential macroevolutionary signature of predation on the evolutionary dynamics of body shape. PMID- 26559955 TI - Latitudinal gradients in biotic niche breadth vary across ecosystem types. AB - Several properties of food webs-the networks of feeding links between species-are known to vary systematically with the species richness of the underlying community. Under the 'latitude-niche breadth hypothesis', which predicts that species in the tropics will tend to evolve narrower niches, one might expect that these scaling relationships could also be affected by latitude. To test this hypothesis, we analysed the scaling relationships between species richness and average generality, vulnerability and links per species across a set of 196 empirical food webs. In estuarine, marine and terrestrial food webs there was no effect of latitude on any scaling relationship, suggesting constant niche breadth in these habitats. In freshwater communities, on the other hand, there were strong effects of latitude on scaling relationships, supporting the latitude niche breadth hypothesis. These contrasting findings indicate that it may be more important to account for habitat than latitude when exploring gradients in food web structure. PMID- 26559956 TI - A female's past experience with predators affects male courtship and the care her offspring will receive from their father. AB - Differential allocation occurs when individuals adjust their reproductive investment based on their partner's traits. However, it remains unknown whether animals differentially allocate based on their partner's past experiences with predation risk. If animals can detect a potential mate's experience with predators, this might inform them about the stress level of their potential mate, the likelihood of parental effects in offspring and/or the dangers present in the environment. Using threespined stickleback (Gasterosteus aculeatus), we examined whether a female's previous experience with being chased by a model predator while yolking eggs affects male mating effort and offspring care. Males displayed fewer conspicuous courtship behaviours towards females that had experienced predation risk in the past compared with unexposed females. This differential allocation extended to how males cared for the resulting offspring of these matings: fathers provided less parental care to offspring of females that had experienced predation risk in the past. Our results show for the first time, to our knowledge, that variation among females in their predator encounters can contribute to behavioural variation among males in courtship and parental care, even when males themselves do not encounter a predator. These results, together with previous findings, suggest that maternal predator exposure can influence offspring development both directly and indirectly, through how it affects father care. PMID- 26559957 TI - New Type of Papillomavirus and Novel Circular Single Stranded DNA Virus Discovered in Urban Rattus norvegicus Using Circular DNA Enrichment and Metagenomics. AB - Rattus norvegicus (R. norvegicus) are ubiquitous and their presence has several effects on the human populations in our urban areas on a global scale. Both historically and presently, this close interaction has facilitated the dissemination of many pathogens to humans, making screening for potentially zoonotic and emerging viruses in rats highly relevant. We have investigated faecal samples from R. norvegicus collected from urban areas using a protocol based on metagenomic enrichment of circular DNA genomes and subsequent sequencing. We found a new type of papillomavirus, with a L1 region 82% identical to that of the known R. norvegicus Papillomavirus 2. Additionally, we found 20 different circular replication associated protein (Rep)-encoding single stranded DNA (CRESS-DNA) virus-like genomes, one of which has homology to the replication associated gene of Beak and feather disease virus. Papillomaviruses are a group of viruses known for their carcinogenic potential, and although they are known to infect several different vertebrates, they are mainly studied and characterised in humans. CRESS-DNA viruses are found in many different environments and tissue types. Both papillomaviruses and CRESS-DNA viruses are known to have pathogenic potential and screening for novel and known viruses in R. norvegicus could help identify viruses with pathogenic potential. PMID- 26559959 TI - 29th Annual Meeting of the Children's Orthopaedics, Frankfurt am Main, 24-25 April 2015. PMID- 26559958 TI - The Distinct Gene Regulatory Network of Myoglobin in Prostate and Breast Cancer. AB - Myoglobin (MB) is not only strongly expressed in myocytes, but also at much lower levels in different cancer entities. 40% of breast tumors are MB-positive, with the globin being co-expressed with markers of tumor hypoxia in a proportion of cases. In breast cancer, MB expression is associated with a positive hormone receptor status and patient prognosis. In prostate cancer, another hormone dependent cancer type, 53% of tumors were recently shown to express MB. Especially in more aggressive prostate cancer specimen MB expression also correlates with increased patient survival rates. Both findings might be due to tumor-suppressing properties of MB in cancer cells. In contrast to muscle, MB transcription in breast and prostate cancer mainly depends on a novel, alternative promoter site. We show here that its associated transcripts can be upregulated by hypoxia and downregulated by estrogens and androgens in MCF7 breast and LNCaP prostate cancer cells, respectively. Bioinformatic data mining of epigenetic histone marks and experimental verification reveal a hitherto uncharacterized transcriptional network that drives the regulation of the MB gene in cancer cells. We identified candidate hormone-receptor binding elements that may interact with the cancer-associated MB promoter to decrease its activity in breast and prostate cancer cells. Additionally, a regulatory element, 250 kb downstream of the promoter, acts as a hypoxia-inducible site within the transcriptional machinery. Understanding the distinct regulation of MB in tumors will improve unraveling the respiratory protein's function in the cancer context and may provide new starting points for developing therapeutic strategies. PMID- 26559960 TI - The complete genome sequence of a novel maize-associated totivirus. AB - Deep sequencing of small RNA (sRNA) populations in maize plants from southwest China resulted in the identification of a previously unknown dsRNA virus with a sequence and genome organization resembling that of a totivirus. The complete viral genome is 3,956 nucleotides in length and contains two open reading frames (ORFs) with the potential to produce a ORF1-ORF2 fusion protein through a -1 ribosomal frameshift translation mechanism. ORF1 encodes the putative capsid protein (CP), whereas the predicted product of ORF2 contains motifs typical of an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis using the amino acid sequences of putative RdRp fusion proteins showed that the new virus was grouped in a clade together with the totiviruses, suggesting that it is a new member of the genus Totivirus of the family Totiviridae. The virus is tentatively named "maize-associated totivirus (MATV)". Our findings demonstrate that it is feasible to identify totiviruses by deep sequencing of small RNAs. PMID- 26559961 TI - The c-Jun N-terminal kinase (JNK) is involved in H5N1 influenza A virus RNA and protein synthesis. AB - The activation of c-jun N-terminal kinases (JNK) was previously shown to be required for efficient influenza A virus replication, although a detailed mechanism has not been reported. In this study, we found that replication of H5N1 influenza virus was influenced by the JNK inhibitor SP600125. The results of time course experiments suggested that SP600125 inhibited an early post-entry step of viral infection but did not affect nucleocytoplasmic trafficking of the viral ribonucleoprotein complex. The levels of influenza virus genomic RNA (vRNA), but not the corresponding cRNA or mRNA, were specifically reduced by SP600125 in virus-infected cells, indicating that the JNK protein is intimately involved in vRNA synthesis. Additionally, SP600125 affected H5N1 virus protein synthesis, because NS1, PB1, PB2, HA and M1 protein production was impaired. Thus, our data demonstrated a critical role of the JNK protein in the regulation of vRNA and protein synthesis during virus infection. This enhances our understanding of the complicated signal transduction network involved in influenza A virus replication. PMID- 26559962 TI - Human transferrin receptor triggers an alternative Tacaribe virus internalization pathway. AB - Tacaribe virus (TCRV) entry occurs by receptor-mediated endocytosis. To explore the entry mechanism used by TCRV, the inhibitory effects of drugs and dominant negative (DN) constructions affecting the main endocytic pathways were analyzed. In cells lacking the human transferrin receptor (hTfR), compounds and DN proteins that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. In contrast, in cells expressing the hTfR, compounds that affect clathrin-mediated endocytosis did not affect TCRV infection. Destabilization of cholesterol-rich plasma membrane microdomains by treatment with nystatin was not able to block virus entry in the presence of hTfR. However methyl-beta-cyclodextrin, which extracts cholesterol from cell membranes, reduced virus internalization in cells expressing the hTfR. Inhibition of dynamin and neutralization of the pH of intracellular vesicles reduced virus internalization in all cell lines tested. Taken together, these results demonstrate that in cells expressing the hTfR, TCRV internalization depends on the presence of cholesterol, dynamin and acidic intracellular vesicles, while in the rest of the cell lines analyzed, clathrin-mediated endocytosis is the main TCRV entry pathway and, as expected, depends on dynamin and acidic intracellular vesicles. These results represent an important contribution to the characterization of the arenavirus replication cycle. PMID- 26559963 TI - Endogenous Cartilage Repair by Recruitment of Stem Cells. AB - Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair. PMID- 26559964 TI - The SAMe-TT2R2 score and decision-making between a vitamin K antagonist or a non vitamin K antagonist oral anticoagulant in patients with atrial fibrillation. AB - Oral anticoagulation therapy is essential in patients with atrial fibrillation and clinicians need guidance on decision-making between the vitamin K antagonists (VKA), e.g. warfarin, or non-vitamin K antagonist oral anticoagulants. Observational studies have shown that patients who receive VKA therapy spend a significant percentage of their time with international normalized ratio values outside of the therapeutic range (time in therapeutic range, TTR <60%.) Recently, a clinical score has been developed with commonly encountered clinical features, the SAMe-TT2R2 score, to help decision-making with regard to whether a patient is likely to do well, or not, with a VKA. Those with a SAMe-TT2R2 score of 0-1 are likely to do well on a VKA, while those with a SAMe-TT2R2 score >= 2 are on probability going to achieve suboptimal TTR. In this article, we provide an overview of the main published retrospective and prospective studies that have validated the SAMe-TT2R2 score and its value for decision-making in daily clinical practice. PMID- 26559965 TI - Effects of Silicate, Phosphate, and Calcium on the Stability of Aldopentoses. AB - Ribose is an important constituent of RNA: ribose connects RNA bases and forms a strand of sugar phosphates. Accumulation of ribose on prebiotic Earth was difficult because of its low stability. Improvement in the yield of ribose by the introduction of borate or silicate in a formose-like reaction has been proposed. The effects of borates have been further analyzed and confirmed in subsequent studies. Nonetheless, the effects of silicates and phosphates remain unclear. In the present study, we incubated aldopentoses in a highly alkaline aqueous solution at a moderate temperature to determine the effects of silicate or phosphate on the degradation rates of ribose and its isomeric aldopentoses. The formation of a complex of silicate (or phosphate) with ribose was also analyzed in experiments with (29)Si and (31)P nuclear magnetic resonance (NMR). We found that silicate or phosphate complexes of ribose were not detectable under our experimental conditions. The stability of ribose and lyxose improved after addition of 40-fold molar excess (relative to a pentose) of sodium silicate or sodium phosphate to the alkaline solution. The stability was not improved further when an 80-fold molar excess of sodium silicate or sodium phosphate was added. Calcium was removed from these solutions by precipitation of calcium salts. The drop in Ca(2+) concentration might have improved the stability of ribose and lyxose, which are susceptible to aldol addition. The improvement of ribose stability by the removal of Ca(2+) and by addition of silicate or phosphate was far smaller than the improvement by borate. Furthermore, all aldopentoses showed similar stability in silicate- and phosphate-containing solutions. These results clearly show that selective stabilization of ribose by borate cannot be replaced by the effects of silicate or phosphate; this finding points to the importance of borate in prebiotic RNA formation. PMID- 26559966 TI - Modelling the Interior Structure of Enceladus Based on the 2014's Cassini Gravity Data. AB - We present a model for the internal structure of Saturn's moon Enceladus. This model allows us to estimate the physical conditions at the bottom of the satellite's potential subsurface water reservoir and to determine the radial distribution of pressure and gravity. This leads to a better understanding of the physical and chemical conditions at the water/rock boundary. This boundary is the most promising area on icy moons for astrobiological studies as it could serve as a potential habitat for extraterrestrial life similar to terrestrial microbes that inhabit rocky mounds on Earth's sea floors. PMID- 26559967 TI - Predictability of horizontal versus vertical muscle surgery outcomes in thyroid eye disease. AB - Surgical repair of vertical muscles in thyroid eye disease (TED) is believed to yield more unpredictable results than horizontal muscle surgery. The purpose of this study is to determine if the short-term outcomes for strabismus surgery in TED are equally predictable for horizontal and vertical muscle surgery. We retrospectively reviewed the charts of 27 consecutive patients who underwent strabismus surgery for TED from a single surgeon's practice. Eligibility for inclusion in the study included biochemically stable thyroid disease for at least a year and stable orthoptic measurements for at least 6 months prior to surgery. Nine patients had surgery only on vertical rectus muscles, three only on horizontal, and fifteen on both vertical and horizontal rectus muscles. Mean follow-up was 2.4 +/- 5.2 months. In primary gaze at 6 m, a mean horizontal deviation of 16.6 +/- 22.3 PD, and a mean vertical deviation of 19.7 +/- 14.1 PD were measured pre-operatively. Post-operatively, this measured 2.3 +/- 8.4 PD horizontally and 2.1 +/- 7.8 PD vertically (p = 0.933). There was no statistically significant difference between post-operative horizontal and vertical deviations in elevation, depression, adduction, and abduction. Nine patients required reoperation to attain satisfactory ocular alignment; seven of these cases involved repeat surgery on vertical muscles, while two cases required operation on both horizontal and vertical muscles. Results suggest that surgical outcomes of both horizontal and vertical muscle surgery are equally predictable in stable TED; however, reoperation rates were higher for vertical muscles compared to horizontal muscles. PMID- 26559968 TI - The use of volume-assured pressure support noninvasive ventilation in acute and chronic respiratory failure: a practical guide and literature review. AB - Noninvasive positive pressure ventilation (NPPV) is an important tool in the management of acute and chronic respiratory failure. Traditionally, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP) have been the most commonly utilized modes for these purposes. Newer hybrid modes of NPPV, such as average volume-assured pressure support (VAPS), combine the properties of both volume- and pressure-controlled NPPV and represent another tool in the treatment of acute and chronic respiratory failure. Evidence demonstrating the superiority of VAPS over BPAP is sparse, but there have been studies that have demonstrated comparable efficacy between the two modes. The use of VAPS in acute hypercapnic respiratory failure has shown better clearance of CO2 compared to BPAP, due to its property of delivering a more assured tidal volume. This, however, did not lead to a decrease in hospital-days or improved mortality, relative to BPAP. The studies evaluating VAPS for chronic respiratory failure involve small sample sizes but have shown some promise. The benefits noted with VAPS, however, did not translate into increased survival, decreased hospitalizations or improved quality of life compared to BPAP. The limited evidence available suggests that VAPS is equally effective in treating acute and chronic respiratory failure compared to BPAP. Overall, the evidence to suggest superiority of one mode over the other is lacking. There is a need for larger studies before firm conclusions can be made. PMID- 26559969 TI - The Structure of the Cyprinid herpesvirus 3 ORF112-Zalpha.Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response. AB - In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Zalpha domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and koi carp, which have PKZ, and encodes the ORF112 protein that itself bears a Zalpha domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Zalpha in complex with an 18-bp CpG DNA repeat, at 1.5 A. We demonstrate that the bound DNA is in the left-handed conformation and identify key interactions for the specificity of ORF112. Localization of ORF112 protein in stress granules induced in Cyprinid herpesvirus 3-infected fish cells suggests a functional behavior similar to that of Zalpha domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI. PMID- 26559970 TI - Vibrio cholerae Porin OmpU Induces Caspase-independent Programmed Cell Death upon Translocation to the Host Cell Mitochondria. AB - Porins, a major class of outer membrane proteins in Gram-negative bacteria, primarily act as transport channels. OmpU is one of the major porins of human pathogen, Vibrio cholerae. In the present study, we show that V. cholerae OmpU has the ability to induce target cell death. Although OmpU-mediated cell death shows some characteristics of apoptosis, such as flipping of phosphatidylserine in the membrane as well as cell size shrinkage and increased cell granularity, it does not show the caspase-3 activation and DNA laddering pattern typical of apoptotic cells. Increased release of lactate dehydrogenase in OmpU-treated cells indicates that the OmpU-mediated cell death also has characteristics of necrosis. Further, we show that the mechanism of OmpU-mediated cell death involves major mitochondrial changes in the target cells. We observe that OmpU treatment leads to the disruption of mitochondrial membrane potential, resulting in the release of cytochrome c and apoptosis-inducing factor (AIF). AIF translocates to the host cell nucleus, implying that it has a crucial role in OmpU-mediated cell death. Finally, we observe that OmpU translocates to the target cell mitochondria, where it directly initiates mitochondrial changes leading to mitochondrial membrane permeability transition and AIF release. Partial blocking of AIF release by cyclosporine A in OmpU-treated cells further suggests that OmpU may be inducing the opening of the mitochondrial permeability transition pore. All of these results lead us to the conclusion that OmpU induces cell death in target cells in a programmed manner in which mitochondria play a central role. PMID- 26559971 TI - Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription. AB - DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+) trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID- 26559972 TI - A Novel Function of Molecular Chaperone HSP70: SUPPRESSION OF ONCOGENIC FOXM1 AFTER PROTEOTOXIC STRESS. AB - The oncogenic transcription factor FOXM1 is overexpressed in the majority of human cancers, and it is a potential target for anticancer therapy. We identified proteasome inhibitors as the first type of drugs that target FOXM1 in cancer cells. Here we found that HSP90 inhibitor PF-4942847 and heat shock also suppress FOXM1. The common effector, which was induced after treatment with proteasome and HSP90 inhibitors or heat shock, was the molecular chaperone HSP70. We show that HSP70 binds to FOXM1 following proteotoxic stress and that HSP70 inhibits FOXM1 DNA-binding ability. Inhibition of FOXM1 transcriptional autoregulation by HSP70 leads to the suppression of FOXM1 protein expression. In addition, HSP70 suppression elevates FOXM1 expression, and simultaneous inhibition of FOXM1 and HSP70 increases the sensitivity of human cancer cells to anticancer drug-induced apoptosis. Overall, we determined the unique and novel mechanism of FOXM1 suppression by proteasome inhibitors. PMID- 26559973 TI - Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit. AB - Influenza virus polymerase catalyzes the transcription of viral mRNAs by a process known as "cap-snatching," where the 5'-cap of cellular pre-mRNA is recognized by the PB2 subunit and cleaved 10-13 nucleotides downstream of the cap by the endonuclease PA subunit. Although this mechanism is common to both influenza A (FluA) and influenza B (FluB) viruses, FluB PB2 recognizes a wider range of cap structures including m(7)GpppGm-, m(7)GpppG-, and GpppG-RNA, whereas FluA PB2 utilizes methylated G-capped RNA specifically. Biophysical studies with isolated PB2 cap-binding domain (PB2(cap)) confirm that FluB PB2 has expanded mRNA cap recognition capability, although the affinities toward m(7)GTP are significantly reduced when compared with FluA PB2. The x-ray co-structures of the FluB PB2(cap) with bound cap analogs m(7)GTP and GTP reveal an inverted GTP binding mode that is distinct from the cognate m(7)GTP binding mode shared between FluA and FluB PB2. These results delineate the commonalities and differences in the cap-binding site between FluA and FluB PB2 and will aid structure-guided drug design efforts to identify dual inhibitors of both FluA and FluB PB2. PMID- 26559974 TI - Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play an important role in regulating electrical activity in the heart and brain. They are gated by the binding of cyclic nucleotides to a conserved, intracellular cyclic nucleotide-binding domain (CNBD), which is connected to the channel pore by a C linker region. Binding of cyclic nucleotides increases the rate and extent of channel activation and shifts it to less hyperpolarized voltages. We probed the allosteric mechanism of different cyclic nucleotides on the CNBD and on channel gating. Electrophysiology experiments showed that cAMP, cGMP, and cCMP were effective agonists of the channel and produced similar increases in the extent of channel activation. In contrast, electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) on the isolated CNBD indicated that the induced conformational changes and the degrees of stabilization of the active conformation differed for the three cyclic nucleotides. We explain these results with a model where different allosteric mechanisms in the CNBD all converge to have the same effect on the C-linker and render all three cyclic nucleotides similarly potent activators of the channel. PMID- 26559975 TI - Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate gamma-Secretase Activities. AB - gamma-Secretase is a multisubunit membrane protein complex containing presenilin (PS1) as a catalytic subunit. Familial Alzheimer disease (FAD) mutations within PS1 were analyzed in yeast cells artificially expressing membrane-bound substrate, amyloid precursor protein, or Notch fused to Gal4 transcriptional activator. The FAD mutations, L166P and G384A (Leu-166 to Pro and Gly-384 to Ala substitution, respectively), were loss-of-function in yeast. We identified five amino acid substitutions that suppress the FAD mutations. The cleavage of amyloid precursor protein or Notch was recovered by the secondary mutations. We also found that secondary mutations alone activated the gamma-secretase activity. FAD mutants with suppressor mutations, L432M or S438P within TMD9 together with a missense mutation in the second or sixth loops, regained gamma-secretase activity when introduced into presenilin null mouse fibroblasts. Notably, the cells with suppressor mutants produced a decreased amount of Abeta42, which is responsible for Alzheimer disease. These results indicate that the yeast system is useful to screen for mutations and chemicals that modulate gamma-secretase activity. PMID- 26559976 TI - Poly(ADP-ribosyl)ation-dependent Transient Chromatin Decondensation and Histone Displacement following Laser Microirradiation. AB - Chromatin undergoes a rapid ATP-dependent, ATM and H2AX-independent decondensation when DNA damage is introduced by laser microirradiation. Although the detailed mechanism of this decondensation remains to be determined, the kinetics of decondensation are similar to the kinetics of poly(ADP-ribosyl)ation. We used laser microirradiation to introduce DNA strand breaks into living cells expressing a photoactivatable GFP-tagged histone H2B. We find that poly(ADP ribosyl)ation mediated primarily by poly(ADP-ribose) polymerase 1 (PARP1) is responsible for the rapid decondensation of chromatin at sites of DNA damage. This decondensation of chromatin correlates temporally with the displacement of histones, which is sensitive to PARP inhibition and is transient in nature. Contrary to the predictions of the histone shuttle hypothesis, we did not find that histone H1 accumulated on poly(ADP-ribose) (PAR) in vivo. Rather, histone H1, and to a lessor extent, histones H2A and H2B were rapidly depleted from the sites of PAR accumulation. However, histone H1 returns to chromatin and the chromatin recondenses. Thus, the PARP-dependent relaxation of chromatin closely correlates with histone displacement. PMID- 26559978 TI - Cardiovascular Risk Factors: From Consolidated Knowledge to a Call for Action. PMID- 26559977 TI - Interleukin-1beta Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin. AB - The secretion of IL-1beta is a central event in the initiation of inflammation. Unlike most other cytokines, the secretion of IL-1beta requires two signals: one signal to induce the intracellular up-regulation of pro-IL-1beta and a second signal to drive secretion of the bioactive molecule. The release of pro-IL-1beta is a complex process involving proteolytic cleavage by caspase-1. However, the exact mechanism of secretion is poorly understood. Here we sought to identify novel proteins involved in IL-1beta secretion and intracellular processing to gain further insights into the mechanism of IL-1 release. A human proteome microarray containing 19,951 unique proteins was used to identify proteins that bind human recombinant pro-IL-1beta. Probes with a signal-to-noise ratio of >3 were defined as biologically relevant. In these analyses, calmodulin was identified as a particularly strong hit, with a signal-to-noise ratio of ~ 11. Using an ELISA-based protein-binding assay, the interaction of recombinant calmodulin with pro-IL-1beta, but not mature IL-1beta, was confirmed and shown to be calcium-dependent. Finally, using small molecule inhibitors, it was demonstrated that both calcium and calmodulin were required for nigericin-induced IL-1beta secretion in THP-1 cells and primary human monocytes. Together, these data suggest that, following calcium influx into the cell, pro-IL-1beta interacts with calmodulin and that this interaction is important for IL-1beta processing and release. PMID- 26559979 TI - Executive Summary of the Guidelines on Stable Coronary Disease. PMID- 26559980 TI - Acute Coronary Syndrome Treatment Costs from the Perspective of the Supplementary Health System. AB - BACKGROUND: Acute coronary syndrome (ACS) is defined as a "group of clinical symptoms compatible with acute myocardial ischemia", representing the leading cause of death worldwide, with a high clinical and financial impact. In this sense, the development of economic studies assessing the costs related to the treatment of ACS should be considered. OBJECTIVE: To evaluate costs and length of hospital stay between groups of patients treated for ACS undergoing angioplasty with or without stent implantation (stent+ / stent-), coronary artery bypass surgery (CABG) and treated only clinically (Clinical) from the perspective of the Brazilian Supplementary Health System (SHS). METHODS: A retrospective analysis of medical claims of beneficiaries of health plans was performed considering hospitalization costs and length of hospital stay for management of patients undergoing different types of treatment for ACS, between Jan/2010 and Jun/2012. RESULTS: The average costs per patient were R$ 18,261.77, R$ 30,611.07, R$ 37,454.94 and R$ 40,883.37 in the following groups: Clinical, stent-, stent+ and CABG, respectively. The average costs per day of hospitalization were R$ 1,987.03, R$ 4,024.72, R$ 6,033.40 and R$ 2,663.82, respectively. The average results for length of stay were 9.19 days, 7.61 days, 6.19 days and 15.20 days in these same groups. The differences were significant between all groups except Clinical and stent- and between stent + and CABG groups for cost analysis. CONCLUSION: Hospitalization costs of SCA are high in the Brazilian SHS, being significantly higher when interventional procedures are required. PMID- 26559981 TI - The Benefits of Prone SPECT Myocardial Perfusion Imaging in Reducing Both Artifact Defects and Patient Radiation Exposure. AB - BACKGROUND: Prone imaging has been demonstrated to minimize diaphragmatic and breast tissue attenuation. OBJECTIVES: To determine the role of prone imaging on the reduction of unnecessary rest perfusion studies and coronary angiographies performed, thus decreasing investigation time and radiation exposure. METHODS: We examined 139 patients, 120 with an inferior wall and 19 with an anterior wall perfusion defect that might represented attenuation artifact. Post-stress images were acquired in both the supine and prone position. Coronary angiography was used as the "gold standard" for evaluating coronary artery patency. The study was terminated and rest imaging was obviated in the presence of complete improvement of the defect in the prone position. Quantitative interpretation was performed. Results were compared with clinical data and coronary angiographic findings. RESULTS: Prone acquisition correctly revealed defect improvement in 89 patients (89/120) with inferior wall and 12 patients (12/19) with anterior wall attenuation artifact. Quantitative analysis demonstrated statistically significant difference in the mean summed stress scores (SSS) of supine and mean SSS of prone studies in patients with disappearing inferior wall defect in the prone position and patent right coronary artery (true negative results). The mean difference between SSS in supine and in prone position was higher with disappearing than with remaining defects. CONCLUSION: Technetium-99m (Tc-99m) tetrofosmin myocardial perfusion imaging with the patient in the prone position overcomes soft tissue attenuation; moreover it provides an inexpensive, accurate approach to limit the number of unnecessary rest perfusion studies and coronary angiographies performed. PMID- 26559982 TI - Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension. AB - BACKGROUND: Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level. OBJECTIVE: Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure. METHODS: Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included. RESULTS: After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced. CONCLUSION: The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis. PMID- 26559983 TI - Anxiety, Depression, and General Psychological Distress in Patients with Coronary Slow Flow. AB - BACKGROUND: The relationship between psychiatric illness and heart disease has been frequently discussed in the literature. The aim of the present study was to investigate the relationship between anxiety, depression and overall psychological distress, and coronary slow flow (CSF). METHODS: In total, 44 patients with CSF and a control group of 50 patients with normal coronary arteries (NCA) were prospectively recruited. Clinical data, admission laboratory parameters, and echocardiographic and angiographic characteristics were recorded. Symptom Checklist 90 Revised (SCL-90-R), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scales were administered to each patient. RESULTS: The groups were comparable with respect to age, sex, and atherosclerotic risk factors. In the CSF group, BAI score, BDI score, and general symptom index were significantly higher than controls (13 [18.7] vs. 7.5 [7], p = 0.01; 11 [14.7] vs. 6.5 [7], p = 0.01; 1.76 [0.81] vs. 1.1[0.24], p = 0.01; respectively). Patients with CSF in more than one vessel had the highest test scores. In univariate correlation analysis, mean thrombolysis in myocardial infarction (TIMI) frame counts were positively correlated with BAI (r = 0.56, p = 0.01), BDI (r = 0.47, p = 0.01), and general symptom index (r = 0.65, p = 0.01). The psychiatric tests were not correlated with risk factors for atherosclerosis. CONCLUSION: Our study revealed higher rates of depression, anxiety, and overall psychological distress in patients with CSF. This conclusion warrants further studies. PMID- 26559984 TI - Mortality from Cardiovascular Diseases in the Elderly: Comparative Analysis of Two Five-year Periods. AB - BACKGROUND: Cardiovascular diseases are the leading cause of death in Brazil. The better understanding of the spatial and temporal distribution of mortality from cardiovascular diseases in the Brazilian elderly population is essential to support more appropriate health actions for each region of the country. OBJECTIVE: To describe and to compare geospatially the rates of mortality from cardiovascular disease in elderly individuals living in Brazil by gender in two 5 year periods: 1996 to 2000 and 2006 to 2010. METHODS: This is an ecological study, for which rates of mortality were obtained from DATASUS and the population rates from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatistica). An average mortality rate for cardiovascular disease in elderly by gender was calculated for each period. The spatial autocorrelation was evaluated by TerraView 4.2.0 through global Moran index and the formation of clusters by the index of local Moran-LISA. RESULTS: There was an increase, in the second 5-year period, in the mortality rates in the Northeast and North regions, parallel to a decrease in the South, South-East and Midwest regions. Moreover, there was the formation of clusters with high mortality rates in the second period in Roraima among females, and in Ceara, Pernambuco and Roraima among males. CONCLUSION: The increase in mortality rates in the North and Northeast regions is probably related to the changing profile of mortality and improvement in the quality of information, a result of the increase in surveillance and health care measures in these regions. PMID- 26559985 TI - Sex-Specific Equations to Estimate Maximum Oxygen Uptake in Cycle Ergometry. AB - BACKGROUND: Aerobic fitness, assessed by measuring VO2max in maximum cardiopulmonary exercise testing (CPX) or by estimating VO2max through the use of equations in exercise testing, is a predictor of mortality. However, the error resulting from this estimate in a given individual can be high, affecting clinical decisions. OBJECTIVE: To determine the error of estimate of VO2max in cycle ergometry in a population attending clinical exercise testing laboratories, and to propose sex-specific equations to minimize that error. METHODS: This study assessed 1715 adults (18 to 91 years, 68% men) undertaking maximum CPX in a lower limbs cycle ergometer (LLCE) with ramp protocol. The percentage error (E%) between measured VO2max and that estimated from the modified ACSM equation (Lang et al. MSSE, 1992) was calculated. Then, estimation equations were developed: 1) for all the population tested (C-GENERAL); and 2) separately by sex (C-MEN and C WOMEN). RESULTS: Measured VO2max was higher in men than in WOMEN: -29.4 +/- 10.5 and 24.2 +/- 9.2 mL.(kg.min)-1 (p < 0.01). The equations for estimating VO2max [in mL.(kg.min)-1] were: C-GENERAL = [final workload (W)/body weight (kg)] x 10.483 + 7; C-MEN = [final workload (W)/body weight (kg)] x 10.791 + 7; and C WOMEN = [final workload (W)/body weight (kg)] x 9.820 + 7. The E% for MEN was: 3.4 +/- 13.4% (modified ACSM); 1.2 +/- 13.2% (C-GENERAL); and -0.9 +/- 13.4% (C MEN) (p < 0.01). For WOMEN: -14.7 +/- 17.4% (modified ACSM); -6.3 +/- 16.5% (C GENERAL); and -1.7 +/- 16.2% (C-WOMEN) (p < 0.01). CONCLUSION: The error of estimate of VO2max by use of sex-specific equations was reduced, but not eliminated, in exercise tests on LLCE. PMID- 26559987 TI - Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy. AB - BACKGROUND: 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes. OBJECTIVE: This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT). METHODS: Prospective observational study of 116 patients aged 64.8 +/- 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves. RESULTS: The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 +/- 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8 , and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping. CONCLUSION: We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT. PMID- 26559986 TI - A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions. AB - BACKGROUND: Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions. OBJECTIVE: to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions. METHODS: Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI. RESULTS: According to the new algorithm, "Ectatic" remodeling pattern was least common, "Complete compensatory" remodeling was present in approximately half of the instances, and "Negative" and "Incomplete compensatory" remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH. CONCLUSION: Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression. PMID- 26559988 TI - Changes in Medical Management after Coronary CT Angiography. AB - INTRODUCTION: Coronary computed tomography angiography (CCTA) allows for non invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients. OBJECTIVE: To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels. METHODS: We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after. RESULTS: A total of 97 patients were included, of which 69% were men, mean age 64 +/- 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive >= 50% lesion. NLDLC was similar at baseline between the grups (138 +/- 52 mg/dL vs. 135 +/- 42 mg/dL vs. 131 +/- 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD. CONCLUSION: Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive >=50% CAD. PMID- 26559989 TI - A Systematic Review on Sleep Duration and Dyslipidemia in Adolescents: Understanding Inconsistencies. PMID- 26559990 TI - Patient Management with Metallic Valve Prosthesis during Pregnancy and Postpartum Period. AB - Prosthetic thrombosis is a rare complication, but it has high mortality and morbidity. Young women of childbearing age that have prosthetic heart valves are at increased risk of thrombosis during pregnancy due to changes in coagulation factors. Anticoagulation with adequate control and frequent follow-up if pregnancy occurs must be performed in order to prevent complications related to anticoagulant use. Surgery remains the treatment of choice for prosthetic heart valve thrombosis in most clinical conditions. Patients with metallic prosthetic valves have an estimated 5% risk of thrombosis during pregnancy and maternal mortality of 1.5% related to the event. Anticoagulation with vitamin K antagonists during pregnancy is related to varying degrees of complications at each stage of the pregnancy and postpartum periods. Warfarin sodium crosses the placental barrier and when used in the first trimester of pregnancy is a teratogenic agent, causing 1-3% of malformations characterized by fetal warfarin syndrome and also constitutes a major cause of miscarriage in 10-30% of cases. In the third trimester and at delivery, the use of warfarin is associated with maternal and neonatal bleeding in approximately 5 to 15% of cases, respectively. On the other hand, inadequate anticoagulation, including the suspension of the oral anticoagulants aiming at fetal protection, carries a maternal risk of about 25% of metallic prosthesis thrombosis, particularly in the mitral valve. This fact is also due to the state of maternal hypercoagulability with activation of coagulation factors V, VI, VII, IX, X, platelet activity and fibrinogen synthesis, and decrease in protein S levels. The Registry of Pregnancy and Cardiac Disease (ROPAC), assessing 212 pregnant women with metal prosthesis, showed that prosthesis thrombosis occurred in 10 (4.7%) patients and maternal hemorrhage in 23.1%, concluding that only 58% of patients with metallic prosthesis had a complication-free pregnancy. PMID- 26559991 TI - Case 4--A 79-Year-Old Man with Congestive Heart Failure Due to Restrictive Cardiomyopathy. PMID- 26559992 TI - Percutaneous Treatment of Mitral Paraprosthetic Regurgitation: an Alternative to Surgery. PMID- 26559993 TI - Persistent Left Superior Vena Cava in Permanent Pacemaker Implantation. PMID- 26559994 TI - Correction: Custo-efetividade de Estatinas em Dose Alta, Moderada e Baixa na Prevencao de Eventos Vasculares no SUS. PMID- 26559995 TI - Does long-term survival exist in pancreatic adenocarcinoma? AB - BACKGROUND: We conducted a population-based study to investigate long-term survival in patients diagnosed with a (suspected) pancreatic adenocarcinoma. METHODS: All patients diagnosed with a pancreatic adenocarcinoma or with a pathologically unverified tumour of the pancreas between 1993 and 2008 in the South of the Netherlands were selected from the Netherlands Cancer Registry (NCR). Medical charts of patients who were alive five years or longer since diagnosis were reviewed. RESULTS: A total of 2 564 patients were included, of whom 1 365 had a pancreatic adenocarcinoma and 1 199 had a pathologically unverified pancreatic tumour. Five-year survival of patients with pathologically verified adenocarcinomas was 1.7% (24 of 1 365 patients). Twenty-one-one of these 24 long-term survivors were among the 207 cases that underwent surgical resection as initial treatment; five-year survival after resection thus being 10.1%. Half of the long-term survivors who underwent surgical resection still eventually died of recurrent disease. Five-year survival among patients with clinically suspected but microscopically unverified pancreatic tumours was 1.3% (16 of 1 199 patients). In 15 of these 16 long-term survivors the initial clinical diagnosis was revised: 14 had benign disease and one a premalignant tumour. CONCLUSIONS: Long-term survival among patients with pancreatic adenocarcinoma is extremely rare. As long-term survival in clinically suspected but pathologically unverified cancer is very unlikely, repeated fine needle aspiration or, preferably, histological biopsy is recommended in order to establish an alternative diagnosis in patients who survive longer than expected (more than 6-12 months). PMID- 26559996 TI - Novel diarylpyrimidines and diaryltriazines as potent HIV-1 NNRTIs with dramatically improved solubility: a patent evaluation of US20140378443A1. AB - Diarylpyrimidine and diaryltriazine derivatives, two representative structurally related classes of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with robust potencies against wild-type and several mutant strains of HIV-1, have attracted more and more attention in the last decade. However, they have been suffering from poor aqueous solubility. A series of novel diarylpyrimidines and diaryltriazines with solubilizing substituents attached to the central rings were reported as potent NNRTIs in the patent US20140378443A1. Some compounds exhibited potencies against wild-type HIV-1 which were comparable or even superior to those of dapivirine, etravirine and rilpivirine. In addition, dramatically enhanced solubilities were observed for these new compounds. Moreover, some structure optimization strategies for improving aqueous solubility are detailed in this review, providing new insights into development of next-generation NNRTIs endowed with favorable solubility. We anticipate that application of these strategies will ultimately lead to discovery of new anti-HIV drug candidates. PMID- 26559997 TI - In memoriam Prof. Deneffe (10-02-1935 - 03-08-2015). PMID- 26559998 TI - Intussusception in Children: A Clinical Review. AB - Intussusception is the most common cause of small bowel obstruction in young infants. Therefore a high index of suspicion and thorough knowledge of this condition is of major importance to be able to diagnose and treat this potentially life threatening condition. In this review we describe epdidemiology, etiology and clinical symptoms of intussuception. Furthermore, we describe diagnostic modalties, especially ultrasonography as the primary choice for diagnosis. In addition, non-operative treatment with different types of enema reduction techniques, and operative treatment by laparotomy and laparoscopy, and outcomes have been reviewed. PMID- 26559999 TI - Making Surgical Care Safer: A Survey on the Implementation of the Checklist by Belgian Surgeons. AB - BACKGROUND: The operating theatre (OT) is a complex environment. The purpose of this survey was to evaluate the implementation of the surgical checklist (SC) at individual level by Belgian Surgeons. METHODS: A Surgical Checklist Questionnaire (SCQ) related to the use of the SC by individual surgeons was attached to the registration website for the 2015 Belgian Surgical Week. It was a one page long, user friendly document, easy to be filled voluntarily and anonymously. RESULTS: Among the 206 surgeons who registered, 81 (39%) filled in the SCQ. The SC template proposed by the WHO "Safe Surgery Saves Lives" initiative was used by 91% of the respondents. However, 89% adapted the SC to their local hospital environment, and 87.5% use it personally for their patients. Since implementation, the SC was never adapted in 46%. According to 21% of respondents, an adverse event was avoided thanks to the SC. Amazingly, SC was considered as an administrative burden by 83% despite the same percentage recognized that patients benefited from the SC. Only 28% of respondents got feedback from the use of the SC. CONCLUSIONS: In this survey, the number of adverse event avoided thanks to the use of the SC demonstrates that SC -represents a simple strategy for addressing surgical patient safety in OT. Nevertheless, SC is still considered by many surgeons as an additional administrative burden and/or as just another gimmick. Further studies are needed to understand why some surgeons are still not willing to adapt to a changing safety culture. PMID- 26560000 TI - The Risk of Malnutrition in Community-Living Elderly on Admission to Hospital for Major Surgery. AB - BACKGROUND: With prevalence rates varying from 10 to 60%, malnutrition in acute hospitals has been acknowledged as a persistent problem in older adults worldwide. This publication is to describe the nutritional condition and associated risk factors of malnutrition in free living elderly on admission to the hospital for major elective surgery. METHODS: A cross sectional, multi-center study in eight surgical wards in three Belgian hospitals. A total of 204 free living elderly, aged 74.8 +/- 6.6 years (Mean +/- SD), on admission to the hospital for major elective surgery and requiring at least 3 days of hospitalization, were consecutively recruited to the study. The nutritional status was assessed on admission and before surgery using the recommended NRS 2002. Data on possible associated factors were collected during post-operative stay using a structured questionnaire. RESULTS: A total of 107 patients (51.4%) were at high risk of malnutrition. In patients older than 70 years (n 150) the risk of malnutrition increased up to 66%. None of the included patients reported preoperative referral to a dietician or nutritional advice nor any prescribed preoperative nutritional supplement. In a multivariate regression analysis it appeared that none of the possible associated factors were significantly associated with malnutrition. CONCLUSIONS: This study confirms the high risk of malnutrition in community living elderly on admission to hospital for elective surgery. According to the NRS-2002 these patients might benefit from nutritional support. However, it appears that nutritional support is not yet commonly implemented in preoperative care for this population at risk. PMID- 26560001 TI - The Prognostic Value of Post-operative Serum C-reactive Protein Level for Survival after Surgery for Colorectal Liver Metastases. AB - BACKGROUND: Increasing emphasis is put on the concept that inflammation is a key player in tumor progression. In the tumor microenvironment, inflammatory cells mediate tumor growth. Elevated C-reactive protein (CRP) levels are identified as being representative of a systemic inflammatory response. Therefore, studies have successfully linked peri-operative CRP levels to survival after surgery for primary colorectal cancer. The aim of this study was to investigate the prognostic value of the post-operative systemic inflammatory response as represented by serum CRP levels after resection of colorectal liver metastases (CRLM). METHODS: Between January 2004 and December 2012, all patients who underwent resection for CRLM were analyzed. The total post-operative acute inflammatory response was objectified by the area under the curve (AUC, trapezium rule). Peak CRP concentrations were determined. The impact of peak CRP values and total CRP response on disease free survival (DFS) and overall survival (OS) was analyzed ; patients were stratified by clinical risk score and/or administration of neo-adjuvant chemotherapy. RESULTS: The final study population consisted of 403 patients. The OS of patients with a high CRP response (AUC, upper quartile) was equal to patients with intermediate (AUC, middle quartiles) or low (AUC, lower quartile) responses. Similarly, total post-operative CRP response did not impact survival when stratifying patients for CRS and/or administration of neo adjuvant chemotherapy. Peak CRP concentrations did not impact survival accordantly. CONCLUSION: Total post-operative inflammatory response, as evidenced by CRP serum levels, had no prognostic value for survival after surgery for CRLM. PMID- 26560002 TI - Overexpression of LC3 in Papillary Thyroid Carcinomas and Lymph Node Metastases. AB - BACKGROUND: Autophagy is believed to be important in tumorigenesis and tumor progression. An antibody to the microtubule-associated protein 1 light chain 3 (LC3), the mammalian homologue of yeast Atg8, recognizing both the soluble (LC3 I) and the membrane-bound form (LC3-II) of the protein, is involved in autophagosome formation during autophagy. The aim of this study was to investigate LC3 expression in papillary thyroid carcinoma (PTC) to elucidate the role of autophagy in human cancer development. METHODS: We investigated the expression of LC3 in human PTC. Tissue samples from 86 cases of papillary thyroid carcinoma were used for the present study. 57 cases of papillary thyroid carcinoma were with lymph node metastasis. The expression of LC3 in tumor, normal tissue adjacent to tumor, distant normal tissue, metastatic lymph node and normal lymph node was examined with immunohistochemistry. The LC3 expression between tumor and normal tissue, metastatic and normal lymph node was also analyzed. RESULTS: The expression of LC3 was detected in 90.7% (78/86) of the tumors and 96.5% (55/57) of metastatic lymph nodes. In contrast, normal tissues adjacent to tumor, distant normal tissues and normal lymph nodes showed no or very weak expression of LC3. LC3 was significantly correlated with tumorigenesis and lymph node metastasis in human PTC. CONCLUSIONS: High expression of LC3 in PTC and metastatic lymph node suggest that Autophagy may play a role in tumorigenesis and lymph node metastasis in human PTC. PMID- 26560003 TI - Effect of Intraperitoneal Thymoquinone on Postoperative Peritoneal Adhesions. AB - BACKGROUND: To determine the effect of thymoquinone on adhesion formation in a rat caecotomy/suture model. MATERIAL AND METHODS: Thirty wistar rats were randomized into three groups: The control group received saline and the thymoquinone group received 10 mg/kg thymoquinone after cecal caecotomy/suture model. In the sham group the abdominal wall was closed without any abrasion to the cecum. On day 15, adhesions were classified, and histopathological samples were taken. RESULTS: There were no incisional hernias or wound dehiscences. In comparing adhesion scores, a significant difference was found between the thymoquinone and the control groups (p < 0.05). The grade of inflammation for the thymoquinone and the sham groups were significantly lower than that of the control group (p < 0.01 and p < 0.001, respectively). Hydroxyproline levels were significantly lower in the sham and thymoquinone groups compared to the control group (p < 0.05). CONCLUSIONS: Based on the results of this study in a rat peritoneal adhesion model, intraperitoneal administered thymoquinone has a strong anti-adhesive effect. PMID- 26560004 TI - Minimally-Invasive Mitral Valve Repair for Isolated Anterior Leaflet Cleft in a 66 Year Old Woman. AB - Mitral valve regurgitation caused by an isolated cleft of the anterior leaflet of the mitral valve is a rare condition, usually corrected early in life. We report the case of a 66 year old patient with an isolated cleft, which was successfully corrected through a minimally-invasive approach, demonstrating good visibility and direct closure of the cleft. PMID- 26560005 TI - When a Mechanical Valve Goes Freestyle: A Patient Tailored Valve-In-Valve Implantation. AB - In case of a redo operation after a full root replacement there are two possible options: replacing the entire root or performing a more conservative valve-in valve implantation. Regarding the relatively high morbidity and mortality of a redo root replacement, the valve-in-valve implantation is the preferred choice if technically feasible. We present the case of a valve-in-valve implantation with a St. Jude mechanical valve in a Medtronic bioprosthesis in a 57-year old man. Follow-up echocardiography after 1 month showed a mean gradient of 17 mmHg and no paravalvular leakage. The combination of a St. Jude bileaflet mechanical valve implanted in a Freestyle root prosthesis has not been described. This case shows that patient tailored treatment with a St. Jude bileaflet mechanical valve in a Freestyle aortic root valve can be safely performed and might be the preferred choice for younger patients, if technically feasible. PMID- 26560006 TI - Inguinal Hernia in an Infant Containing Uterus, Bilateral Fallopian Tubes and Ovaries. AB - Infants are frequently diagnosed with an inguinal hernia. The hernia can contain intestinal structures or in female infants even the reproductive organs. However it is very exceptional that an inguinal hernia contains the entire uterus, fallopian tubes and both ovaries. In this report a case is described of a two month-old infant which was diagnosed and semi-urgently operated with a right sided inguinal hernia containing all the aforementioned anatomical structures. PMID- 26560007 TI - Popliteal Arteriovenous Fistula Following Total Knee Arthroplasty. AB - Postoperative popliteal arteriovenous fistula is a very rare complication. We report a unique asymptomatic fistula in a 77-year-old male patient, seven months after total knee replacement. The diagnosis was suspected by a clinical palpable thrill and confirmed with a typical doppler ultrasound signaling. This vascular malformation was successfully treated by surgical resection of the fistula. Referring to the literature, considering the management of popliteal aneurysms, we suggest to prefer an open procedure in patients who are in good general condition. PMID- 26560008 TI - Gastric Duplication Cyst with Respiratory Epithelium: a Rare Entity. AB - Gastric duplication cyst is an uncommon entity and management is principally surgical. Diagnosis is often delayed because of the non-specific nature of symptoms. The authors report one case of gastric duplication cyst incidentally diagnosed in a 23-year-old man. He had no specific symptoms but follow up of the unknown retro gastric mass showed an increase in size and cholelithiasis. Magnetic resonance imaging (MRI) was not useful for diagnosis but an endoscopic ultrasound suggested a GIST. The growing size of the mass led to a laparoscopic resection. Histopathology showed a gastric duplication cyst boarded with gastric and respiratory ciliated epithelium. This respiratory differenciation is extremely rare. Our patient is the 25th case reported in the literature. The embryologic origin, diagnosis tools and treatment of those rare cysts are briefly reviewed. PMID- 26560009 TI - Microsurgical Reconstruction of the Nasal Ala using a Composite Auricular Graft Based on the Superficial Temporal Vessels. AB - Full-thickness defects of the nasal ala can be challenging to reconstruct. The original texture, color and shape of this specific aesthetic unit requires careful planning of the surgical approach and technique in order to minimize donor-site morbidity and repetitive procedures. We describe the use of the chondrocutaneous composite auricular graft to -reconstruct a full-thickness defect of the ala of the nose with a successful and aesthetically pleasing outcome. PMID- 26560010 TI - The "Feeling of Movement": Notes on the Rorschach Human Movement Response. AB - Human movement responses (M) on the Rorschach have been traditionally viewed as lying neither completely in the inkblot (external reality) nor within the subject's mind (inner world). The authors contend that M is not reducible to the "body that I have" but to the "body that I am," which is a higher level organization of bottom-up and top-down brain networks, integrating body implicit awareness, psychological functioning, and social cognition. Two sources of evidence suggest the close relationship among M, psychological functions, and brain mechanisms. One comes from meta-analytical evidence supporting the close association between M and higher level cognitive functioning or empathy. The second comes from some preliminary studies showing that M activates brain circuits included in the mirror neuron system (MNS). Two conclusions can be drawn: (a) M is related to the effective use of the mentalization function; and (b) future neuroscientific investigations could lead to an understanding of the neuropsychological mechanisms underlying Rorschach responses and variables. PMID- 26560011 TI - Clinically silent myocardial scars are common in middle aged and older people, study finds. PMID- 26560012 TI - Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1). AB - 1. Fructus psoraleae (FP) is the dried ripe seeds of Psoralea corylifolia L. (Fabaceae) widely used in Asia, and has been reported to exert important biochemical and pharmacological activities. The adverse effects of FP remain unclear. The present study aims to determine the inhibition of human carboxylesterase 1 (CES1) by FP's major ingredients, including neobavaisoflavone, corylifolinin, coryfolin, psoralidin, corylin and bavachinin. 2. The probe substrate of CES1 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) was derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT), and human liver microsomes (HLMs)-catalyzed BMBT metabolism was used to phenotype the activity of CES1. In silico docking method was employed to explain the inhibition mechanism. 3. All the tested compounds exerted strong inhibition towards the activity of CES1 in a concentration-dependent behavior. Furthermore, the inhibition kinetics was determined for the inhibition of neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin towards CES1. Both Dixon and Lineweaver-Burk plots showed that neobavaisoflavone, corylifolinin, coryfolin and corylin noncompetitively inhibited the activity of CES1, and bavachinin competitively inhibited the activity of CES1. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 9.4, 1.9, 0.7 and 0.5 MUM for neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin, respectively. In conclusion, the inhibition behavior of CES1 by the FP's constituents was given in this article, indicating the possible adverse effects of FP through the disrupting CES1-catalyzed metabolism of endogenous substances and xenobiotics. PMID- 26560013 TI - Barriers to workplace HIV testing in South Africa: a systematic review of the literature. AB - Low workplace HIV testing uptake makes effective management of HIV and AIDS difficult for South African organisations. Identifying barriers to workplace HIV testing is therefore crucial to inform urgently needed interventions aimed at increasing workplace HIV testing. This study reviewed literature on workplace HIV testing barriers in South Africa. Pubmed, ScienceDirect, PsycInfo and SA Publications were systematically researched. Studies needed to include measures to assess perceived or real barriers to participate in HIV Counselling and Testing (HCT) at the workplace or discuss perceived or real barriers of HIV testing at the workplace based on collected data, provide qualitative or quantitative evidence related to the research topic and needed to refer to workplaces in South Africa. Barriers were defined as any factor on economic, social, personal, environmental or organisational level preventing employees from participating in workplace HIV testing. Four peer-reviewed studies were included, two with quantitative and two with qualitative study designs. The overarching barriers across the studies were fear of compromised confidentiality, being stigmatised or discriminated in the event of testing HIV positive or being observed participating in HIV testing, and a low personal risk perception. Furthermore, it appeared that an awareness of an HIV-positive status hindered HIV testing at the workplace. Further research evidence of South African workplace barriers to HIV testing will enhance related interventions. This systematic review only found very little and contextualised evidence about workplace HCT barriers in South Africa, making it difficult to generalise, and not really sufficient to inform new interventions aimed at increasing workplace HCT uptake. PMID- 26560014 TI - Interventions for treating proximal humeral fractures in adults. AB - BACKGROUND: Fracture of the proximal humerus, often termed shoulder fracture, is a common injury in older people. The management of these fractures varies widely. This is an update of a Cochrane Review first published in 2001 and last updated in 2012. OBJECTIVES: To assess the effects (benefits and harms) of treatment and rehabilitation interventions for proximal humeral fractures in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and other databases, conference proceedings and bibliographies of trial reports. The full search ended in November 2014. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) and quasi-randomised controlled trials pertinent to the management of proximal humeral fractures in adults. DATA COLLECTION AND ANALYSIS: Both review authors performed independent study selection, risk of bias assessment and data extraction. Only limited meta analysis was performed. MAIN RESULTS: We included 31 heterogeneous RCTs (1941 participants). Most of the 18 separate treatment comparisons were tested by small single-centre trials. The main exception was the surgical versus non-surgical treatment comparison tested by eight trials. Except for a large multicentre trial, bias in these trials could not be ruled out. The quality of the evidence was either low or very low for all comparisons except the largest comparison.Nine trials evaluated non-surgical treatment in mainly minimally displaced fractures. Four trials compared early (usually one week) versus delayed (three or four weeks) mobilisation after fracture but only limited pooling was possible and most of the data were from one trial (86 participants). This found some evidence that early mobilisation resulted in better recovery and less pain in people with mainly minimally displaced fractures. There was evidence of little difference between the two groups in shoulder complications (2/127 early mobilisation versus 3/132 delayed mobilisation; 4 trials) and fracture displacement and non-union (2/52 versus 1/54; 2 trials).One quasi-randomised trial (28 participants) found the Gilchrist-type sling was generally more comfortable than the Desault-type sling (body bandage). One trial (48 participants) testing pulsed electromagnetic high-frequency energy provided no evidence. Two trials (62 participants) provided evidence indicating little difference in outcome between instruction for home exercises versus supervised physiotherapy. One trial (48 participants) reported, without presentable data, that home exercise alone gave better early and comparable long-term results than supervised exercise in a swimming pool plus home exercise.Eight trials, involving 567 older participants, evaluated surgical intervention for displaced fractures. There was high quality evidence of no clinically important difference in patient-reported shoulder and upper-limb function at one- or two-year follow-up between surgical (primarily locking plate fixation or hemiarthroplasty) and non-surgical treatment (sling immobilisation) for the majority of displaced proximal humeral fractures; and moderate quality evidence of no clinically important difference between the two groups in quality of life at two years (and at interim follow-ups at six and 12 months). There was moderate quality evidence of little difference between groups in mortality in the surgery group (17/248 versus 12/248; risk ratio (RR) 1.40 favouring non-surgical treatment, 95% confidence interval (CI) 0.69 to 2.83; P = 0.35; 6 trials); only one death was explicitly linked with the treatment. There was moderate quality evidence of a higher risk of additional surgery in the surgery group (34/262 versus 16/261; RR 2.06, 95% CI 1.18 to 3.60; P = 0.01; 7 trials). Although there was moderate evidence of a higher risk of adverse events after surgery, the 95% confidence intervals for adverse events also included the potential for a greater risk of adverse events after non-surgical treatment.Different methods of surgical management were tested in 12 trials. One trial (57 participants) comparing two types of locking plate versus a locking nail for treating two-part surgical neck fractures found some evidence of slightly better function after plate fixation but also of a higher rate of surgically-related complications. One trial (61 participants) comparing a locking plate versus minimally invasive fixation with distally inserted intramedullary K-wires found little difference between the two implants at two years. Compared with hemiarthroplasty, one trial (32 participants) found similar results with locking plate fixation in function and re-operation rates, whereas another trial (30 participants) reported all five re operations occurred in the tension-band fixation group. One trial (62 participants) found better patient-rated (Quick DASH) and composite shoulder function scores at a minimum of two years follow-up and a lower incidence of re operation and complications after reverse shoulder arthroplasty (RSA) compared with hemiarthroplasty.No important between-group differences were found in one trial (120 participants) comparing the deltoid-split approach versus deltopectoral approach for non-contact bridging plate fixation, and two trials (180 participants) comparing 'polyaxial' and 'monaxial' screws in locking plate fixation. One trial (68 participants) produced some preliminary evidence that tended to support the use of medial support locking screws in locking plate fixation. One trial (54 participants) found fewer adverse events, including re operations, for the newer of two types of intramedullary nail. One trial (35 participants) found better functional results for one of two types of hemiarthroplasty. One trial (45 participants) found no important effects of tenodesis of the long head of the biceps for people undergoing hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial: 64 participants) or hemiarthroplasty (one trial: 49 participants). AUTHORS' CONCLUSIONS: There is high or moderate quality evidence that, compared with non surgical treatment, surgery does not result in a better outcome at one and two years after injury for people with displaced proximal humeral fractures involving the humeral neck and is likely to result in a greater need for subsequent surgery. The evidence does not cover the treatment of two-part tuberosity fractures, fractures in young people, high energy trauma, nor the less common fractures such as fracture dislocations and head splitting fractures.There is insufficient evidence from RCTs to inform the choices between different non surgical, surgical, or rehabilitation interventions for these fractures. PMID- 26560016 TI - Caregivers' nutrition knowledge and attitudes are associated with household food diversity and children's animal source food intake across different agro ecological zones in Ghana. AB - Caregivers' nutrition knowledge and attitudes may influence the variety of foods available in the household and the quality of children's diets. To test the link, this study collected data on caregivers' (n 608) nutrition knowledge and feeding attitudes as well as the diets of their household and of their 2-5-year-old children in twelve rural communities nested in the three main agro-ecological zones of Ghana. Household foods and children's animal source foods (ASF) consumed in the past 7 d were categorised into one of fourteen and ten groups, respectively. About 28 % of caregivers believed that their children needed to be fed only 2-3 times/d. Reasons for having adult supervision during child meal times, feeding diverse foods, prioritising a child to receive ASF and the perceived child benefits of ASF differed across zones (P<0.001). Households with caregivers belonging to the highest tertile of nutrition knowledge and attitude scores consumed more diverse diets compared with those of caregivers in the lowest tertile group (11.2 (sd 2.2) v. 10.0 (sd 2.4); P<0.001). After controlling for the effect of agro-ecological zone, caregivers' nutrition knowledge and feeding attitudes positively predicted household dietary diversity and the frequency and diversity of children's ASF intakes (P<0.001). The number of years of formal education of caregivers also positively predicted household dietary diversity and children's ASF diversity (P<0.001). A key component to improving child nutrition is to understand the context-specific nutrition knowledge and feeding attitudes in order to identify relevant interventions. PMID- 26560015 TI - Immune correlates for dengue vaccine development. AB - Dengue virus is the leading cause of vector-borne viral disease with four serotypes in circulation. Vaccine development has been complicated by the potential for both protection and disease enhancement during heterologous infection. Secondary infection triggers cross-reactive immune memory responses that have varying functional and epitope specificities that determine protection or risk. Strongly neutralizing antibodies to quaternary epitopes may be especially important for virus neutralization. Cell-mediated immunity dominated by Th1 functions may also play an important role. Determining an immune correlate of protection or risk would be highly beneficial for vaccine development but is hampered by mechanistic uncertainties and assay limitations. Clinical efficacy trials and human infection models along with a systems approach may provide future opportunities to elucidate such correlates. PMID- 26560017 TI - Responsiveness, Sensitivity, and Minimally Detectable Difference of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension, Version 1.0. AB - As spinal cord injury (SCI) trials begin to involve subjects with acute cervical SCI, establishing the property of an upper limb outcome measure to detect change over time is critical for its usefulness in clinical trials. The objectives of this study were to define responsiveness, sensitivity, and minimally detectable difference (MDD) of the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP). An observational, longitudinal study was conducted. International Standards of Neurological Classification of SCI (ISNCSCI), GRASSP, Capabilities of Upper Extremity Questionnaire (CUE-Q), and Spinal Cord Independence Measure (SCIM) were administered 0-10 days, 1, 3, 6, and 12 months post-injury. Standardized Response Means (SRM) for GRASSP and ISNCSCI measures were calculated. Longitudinal construct validity was calculated using Pearson correlation coefficients. Smallest real difference for all subtests was calculated to define the MDD values for all GRASSP subtests. Longitudinal construct validity demonstrated GRASSP and all external measures to be responsive to neurological change for 1 year post-injury. SRM values for the GRASSP subtests ranged from 0.25 to 0.85 units greater than that for ISNCSCI strength and sensation, SCIM-SS, and CUE-Q. MDD values for GRASSP subtests ranged from 2-5 points. GRASSP demonstrates good responsiveness and excellent sensitivity that is superior to ISNCSCI and SCIM III. MDD values are useful in the evaluation of interventions in both clinical and research settings. The responsiveness and sensitivity of GRASSP make it a valuable condition-specific measure in tetraplegia, where changes in upper limb neurological and functional outcomes are essential for evaluating the efficacy of interventions. PMID- 26560018 TI - Treatment of massive subcutaneous emphysema with aspiration drainage. PMID- 26560020 TI - Photodamage to the oxygen evolving complex of photosystem II by visible light. AB - Light damages photosynthetic machinery, primarily photosystem II (PSII), and it results in photoinhibition. A new photodamage model, the two-step photodamage model, suggests that photodamage to PSII initially occurs at the oxygen evolving complex (OEC) by light energy absorbed by manganese and that the PSII reaction center is subsequently damaged by light energy absorbed by photosynthetic pigments due to the limitation of electrons to the PSII reaction center. However, it is still uncertain whether this model is applicable to photodamage to PSII under visible light as manganese absorbs visible light only weakly. In the present study, we identified the initial site of photodamage to PSII upon illumination of visible light using PSII membrane fragments isolated from spinach leaves. When PSII samples were exposed to visible light in the presence of an exogenous electron acceptor, both PSII total activity and the PSII reaction centre activity declined due to photodamage. The supplemental addition of an electron donor to the PSII reaction centre alleviated the decline of the reaction centre activity but not the PSII total activity upon the light exposure. Our results demonstrate that visible light damages OEC prior to photodamage to the PSII reaction center, consistent with two-step photodamage model. PMID- 26560019 TI - Lean techniques to improve the flow of critically ill patients in a health region with its epicenter in the intensive care unit of a reference hospital. AB - OBJECTIVE: To analyze whether the application of Lean techniques to improve the flow of critically ill patients in a health region with its epicenter in the intensive care unit (ICU) of a reference hospital. DESIGN: Observational study with pre and post intervention analysis. SETTING: ICU of a reference hospital. PATIENTS: We design projects and a value stream map of flow and compared pre and post intervention. INTERVENTIONS: We recorded demographic data, patient transfers by EMS for lack of beds and delay times in the discharge from ICU to ward. Multidisciplinary meetings and perform daily visual panel, with high priority ICU discharge. We promote temporary relocation of critically ill patients in other special areas of the hospital. We performed a professional satisfaction questionnaire with pre and post implementation of process. We make a statistical analysis of pre and post-intervention comparisons. RESULTS: We planned for 2013 and progressively implemented in 2014. Analysis of patients entering the critical process flow 1) evaluate patients who must transfer for lack of beds, focusing on a diagnosis: pre 10/22 vs. 3/21 post (P=.045); 2) analysis of time delay in the discharge from the ICU to ward: 360.8+/-163.9minutes in the first period vs. 276.7+/-149.5 in the second (P=.036); and 3) personal professional satisfaction questionnaire, with 6.6+/-1.5 points pre vs. 7.5+/-1.1 in post (P=.001). Analysis of indicators such as the ICU acquired infections, length of ICU stay, the rate of re-admissions and mortality, with no significant differences between the two periods. CONCLUSIONS: The application of Lean techniques in the critically ill process had a positive impact on improving patient flow within the health region, noting a decrease of transfers outside the region due to lack of beds, reduced delayed discharge from ICU to conventional ward and increased satisfaction of ICU professionals. PMID- 26560021 TI - Radiologic bone adaptations on a cementless short-stem shoulder prosthesis. AB - BACKGROUND: This study evaluated the timing and location of radiologic bone adaptations related to shoulder arthroplasty using a single type of cementless short-stem shoulder prosthesis. METHODS: Uncemented short-stem shoulder arthroplasties were evaluated in 52 patients at a mean age of 71.6 years (range, 58.1-86.6) with a minimum clinical and radiologic follow-up of 2 years (mean, 32 months; range, 23-52 months). All radiographs were analyzed for inclination of the stem, filling ratio of metaphysis and diaphysis, bone remodeling around the stem, radiolucent lines around the glenoid, and subsidence of the humeral stem. Finally, the radiographic and clinical findings were compared between patients with low and high bone adaptations. RESULTS: At final follow-up, no loosening, subsidence, or osteolysis was seen. High bone adaptations were present in 27 patients (51.9%). Cortical thinning and osteopenia in the medial cortex (82.7%) and spot welds in the lateral cortex (78.6%) were the most frequently occurring bone adaptations. Patients with high bone adaptations had significantly higher metaphyseal (0.60 +/- 0.05 vs. 0.56 +/- 0.06; P = .024) and diaphyseal filling ratio (0.66 +/- 0.04 vs. 0.61 +/- 0.06; P = .019) at 2-year follow-up than patients with low bone adaptations. Clinical outcome was not influenced by the radiographic changes. CONCLUSION: The clinical and radiologic results of the short-stem shoulder arthroplasty are comparable to those with the third and fourth generations of standard stem arthroplasty. Higher filling ratios in the metaphysis and the diaphysis were significantly associated with the occurrence of high bone adaptations. PMID- 26560023 TI - Is there a survival benefit from increased intensity of CEA monitoring after primary resection of colorectal cancer? PMID- 26560022 TI - IL-36alpha: a novel cytokine involved in the catabolic and inflammatory response in chondrocytes. AB - Recent studies confer to IL-36alpha pro-inflammatory properties. However, little is known about the expression and function of IL-36alpha in cartilage. This study sought to analyze the expression of IL-36alpha in healthy and OA cartilage. Next, we determined the effects of recombinant IL-36alpha on catabolism and inflammation in chondrocytes. For completeness, part of the signaling pathway elicited by IL-36alpha was also explored. IL-36alpha expression was evaluated by immunohistochemistry and RT-qPCR. Expression of MMP-13, NOS2 and COX-2 was also determined in OA articular chondrocytes treated with recombinant IL-36alpha. IkappaB-alpha and P-p38 was explored by western blot. We observed a low constitutive expression of IL-36alpha in healthy human chondrocytes. However, OA chondrocytes likely expressed more IL-36alpha than healthy chondrocytes. In addition, immune cells infiltrated into the joint and PBMCs express higher levels of IL-36alpha in comparison to chondrocytes. OA chondrocytes, treated with IL 36alpha, showed significant increase in the expression of MMP-13, NOS2 and COX-2. Finally, IL-36alpha stimulated cells showed NFkappaB and p38 MAPK activated pathways. IL-36alpha acts as a pro-inflammatory cytokine at cartilage level, by increasing the expression of markers of inflammation and cartilage catabolism. Like other members of IL-1 family, IL-36alpha acts through the activation of NFkappaB and p38 MAPK pathway. PMID- 26560024 TI - Procalcitonin levels predict infectious complications and response to treatment in patients undergoing cytoreductive surgery for peritoneal malignancy. AB - BACKGROUND: Cytoreductive-surgery for peritoneal-malignancy (PM) involves extensive intra-abdominal surgery and a massive post-operative systemic inflammatory-response (SIRS). It is often challenging to differentiate SIRS that are solely surgery-associated from those of post-operative infections. White-Cell Counts (WCC) and C-Reactive-Protein (CRP) are routinely used as markers for infection, but are non-specific and their elevation is often delayed in PM cases. Other markers need to be evaluated to assist early identification/prediction of post-operative infections. METHODOLOGY: Prospective evaluation of serum procalcitonin (PCT), CRP and WCC in 50 patients pre-operatively (Day0), and on post-operative days (POD) 1, 3 & 6, following cytoreductive-surgery with or without splenectomy. RESULTS: Day0 PCT, CRP and WCC values were within normal limits, but increasing physiologically in post-operative period without infection, with noticeable higher PCT in splenectomized patients. In our cohort post-operative infections were diagnosed in 14 patients, often within 48 h. There was a trend for faster rise in serum PCT on POD1 compared to CRP and WCC, and faster PCT decline following appropriate therapy on POD3 and POD6 when infected cases were clinically resolving while WCC and CRP continued to rise, particularly in non-spelenectomised patients. The AUC on POD1 was significantly higher for PCT (0.689) vs. WCC (0.476) and CRP (0.477) (p = 0.04). Sensitivity, specificity, positive-predictive-value and negative-predictive-values for PCT ranged between (57%-100%), (22%-74%), (33%-47%) & (81%-100%), for CRP (28%-78%), (5.5%-86%), (18%-44.4%) & (40%-75.5%) and for WCC (14%-26.5%), (65.5-80.5%), (22%-25%), (67% 70%) respectively. CONCLUSION: PCT, like WCC and CRP, needs to be interpreted with extreme cautions in the context of infections post-cytoreductive-surgery and should only be used in association with other clinical and investigational findings. PMID- 26560025 TI - Thermal biases and vulnerability to warming in the world's marine fauna. AB - A critical assumption underlying projections of biodiversity change associated with global warming is that ecological communities comprise balanced mixes of warm-affinity and cool-affinity species which, on average, approximate local environmental temperatures. Nevertheless, here we find that most shallow water marine species occupy broad thermal distributions that are aggregated in either temperate or tropical realms. These distributional trends result in ocean-scale spatial thermal biases, where communities are dominated by species with warmer or cooler affinity than local environmental temperatures. We use community-level thermal deviations from local temperatures as a form of sensitivity to warming, and combine these with projected ocean warming data to predict warming-related loss of species from present-day communities over the next century. Large changes in local species composition appear likely, and proximity to thermal limits, as inferred from present-day species' distributional ranges, outweighs spatial variation in warming rates in contributing to predicted rates of local species loss. PMID- 26560026 TI - Cell fate: Transition loses its invasive edge. PMID- 26560027 TI - Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. AB - Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells. Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 * 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P < 0.0001). We demonstrate allelic imbalance favouring the G-containing strand in tumours heterozygous for this SNP, as demonstrated both by RNA sequencing (P < 0.0001) and reporter assays (P = 0.002). These findings indicate that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells. PMID- 26560028 TI - Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. AB - Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis despite current best therapies; therefore new treatment strategies are urgently required. Numerous studies have suggested that epithelial-to-mesenchymal transition (EMT) contributes to early-stage dissemination of cancer cells and is pivotal for invasion and metastasis of PDAC. EMT is associated with phenotypic conversion of epithelial cells into mesenchymal-like cells in cell culture conditions, although such defined mesenchymal conversion (with spindle-shaped morphology) of epithelial cells in vivo is rare, with quasi-mesenchymal phenotypes occasionally observed in the tumour (partial EMT). Most studies exploring the functional role of EMT in tumours have depended on cell-culture induced loss-of-function and gain-of-function experiments involving EMT-inducing transcription factors such as Twist, Snail and Zeb1 (refs 2, 3, 7-10). Therefore, the functional contribution of EMT to invasion and metastasis remains unclear, and genetically engineered mouse models to address a causal connection are lacking. Here we functionally probe the role of EMT in PDAC by generating mouse models of PDAC with deletion of Snail or Twist, two key transcription factors responsible for EMT. EMT suppression in the primary tumour does not alter the emergence of invasive PDAC, systemic dissemination or metastasis. Suppression of EMT leads to an increase in cancer cell proliferation with enhanced expression of nucleoside transporters in tumours, contributing to enhanced sensitivity to gemcitabine treatment and increased overall survival of mice. Collectively, our study suggests that Snail- or Twist-induced EMT is not rate-limiting for invasion and metastasis, but highlights the importance of combining EMT inhibition with chemotherapy for the treatment of pancreatic cancer. PMID- 26560029 TI - Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum. AB - Plant genomes, and eukaryotic genomes in general, are typically repetitive, polyploid and heterozygous, which complicates genome assembly. The short read lengths of early Sanger and current next-generation sequencing platforms hinder assembly through complex repeat regions, and many draft and reference genomes are fragmented, lacking skewed GC and repetitive intergenic sequences, which are gaining importance due to projects like the Encyclopedia of DNA Elements (ENCODE). Here we report the whole-genome sequencing and assembly of the desiccation-tolerant grass Oropetium thomaeum. Using only single-molecule real time sequencing, which generates long (>16 kilobases) reads with random errors, we assembled 99% (244 megabases) of the Oropetium genome into 625 contigs with an N50 length of 2.4 megabases. Oropetium is an example of a 'near-complete' draft genome which includes gapless coverage over gene space as well as intergenic sequences such as centromeres, telomeres, transposable elements and rRNA clusters that are typically unassembled in draft genomes. Oropetium has 28,466 protein coding genes and 43% repeat sequences, yet with 30% more compact euchromatic regions it is the smallest known grass genome. The Oropetium genome demonstrates the utility of single-molecule real-time sequencing for assembling high-quality plant and other eukaryotic genomes, and serves as a valuable resource for the plant comparative genomics community. PMID- 26560030 TI - Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. AB - Cancer cells hijack and remodel existing metabolic pathways for their benefit. Argininosuccinate synthase (ASS1) is a urea cycle enzyme that is essential in the conversion of nitrogen from ammonia and aspartate to urea. A decrease in nitrogen flux through ASS1 in the liver causes the urea cycle disorder citrullinaemia. In contrast to the well-studied consequences of loss of ASS1 activity on ureagenesis, the purpose of its somatic silencing in multiple cancers is largely unknown. Here we show that decreased activity of ASS1 in cancers supports proliferation by facilitating pyrimidine synthesis via CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) activation. Our studies were initiated by delineating the consequences of loss of ASS1 activity in humans with two types of citrullinaemia. We find that in citrullinaemia type I (CTLN I), which is caused by deficiency of ASS1, there is increased pyrimidine synthesis and proliferation compared with citrullinaemia type II (CTLN II), in which there is decreased substrate availability for ASS1 caused by deficiency of the aspartate transporter citrin. Building on these results, we demonstrate that ASS1 deficiency in cancer increases cytosolic aspartate levels, which increases CAD activation by upregulating its substrate availability and by increasing its phosphorylation by S6K1 through the mammalian target of rapamycin (mTOR) pathway. Decreasing CAD activity by blocking citrin, the mTOR signalling, or pyrimidine synthesis decreases proliferation and thus may serve as a therapeutic strategy in multiple cancers where ASS1 is downregulated. Our results demonstrate that ASS1 downregulation is a novel mechanism supporting cancerous proliferation, and they provide a metabolic link between the urea cycle enzymes and pyrimidine synthesis. PMID- 26560031 TI - Corrigendum: Regulatory analysis of the C. elegans genome with spatiotemporal resolution. PMID- 26560032 TI - Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments. AB - Contraction of both skeletal muscle and the heart is thought to be controlled by a calcium-dependent structural change in the actin-containing thin filaments, which permits the binding of myosin motors from the neighbouring thick filaments to drive filament sliding. Here we show by synchrotron small-angle X-ray diffraction of frog (Rana temporaria) single skeletal muscle cells that, although the well-known thin-filament mechanism is sufficient for regulation of muscle shortening against low load, force generation against high load requires a second permissive step linked to a change in the structure of the thick filament. The resting (switched 'OFF') structure of the thick filament is characterized by helical tracks of myosin motors on the filament surface and a short backbone periodicity. This OFF structure is almost completely preserved during low-load shortening, which is driven by a small fraction of constitutively active (switched 'ON') myosin motors outside thick-filament control. At higher load, these motors generate sufficient thick-filament stress to trigger the transition to its long-periodicity ON structure, unlocking the major population of motors required for high-load contraction. This concept of the thick filament as a regulatory mechanosensor provides a novel explanation for the dynamic and energetic properties of skeletal muscle. A similar mechanism probably operates in the heart. PMID- 26560034 TI - Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way. AB - The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon. PMID- 26560033 TI - Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. AB - The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We show that within a predominantly epithelial primary tumour, a small proportion of tumour cells undergo EMT. Notably, lung metastases mainly consist of non-EMT tumour cells that maintain their epithelial phenotype. Inhibiting EMT by overexpressing the microRNA miR-200 does not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment owing to reduced proliferation, apoptotic tolerance and increased expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment. PMID- 26560035 TI - Ecology: Ecosystem vulnerability to ocean warming. PMID- 26560036 TI - Linked color imaging technology facilitates early detection of flat gastric cancers. AB - Conventional endoscopy can miss flat early gastric cancers (0-IIb) because they may not be visible. We treated a patient with synchronous flat early gastric cancers missed by conventional white-light endoscopy (WLE). A 74-year-old Japanese male was referred for endoscopic submucosal dissection (ESD) of a depressed-type early gastric cancer (0-IIc) on the posterior wall of the antrum. Linked color imaging (LCI) detected two flat reddish lesions (0-IIb) measuring 30 mm and 10 mm in diameter in the distal body and prepyloric area, respectively, which had not been detected by conventional WLE. LCI clearly demonstrated the line of demarcation between the malignant lesion and the surrounding mucosa without magnification. Flat early gastric cancers were suspected because both lesions had irregular surface patterns using magnifying blue laser imaging (BLI). An additional depressed lesion (0-IIc) was detected by laser WLE along the greater curvature in the antrum. Magnifying BLI suggested a malignant lesion. Histological examination of biopsy specimens revealed atypical glands in all four lesions. ESD of these lesions was performed. Pathological examination of the resected specimens confirmed well-differentiated adenocarcinoma localized to the mucosa in all four lesions. Flat early gastric cancers became clearly visible using new endoscopic technology. PMID- 26560037 TI - Concerns over your recent paper on risperidone long-acting injectable for treatment-resistant schizophrenia. PMID- 26560038 TI - Controlling the peripheral clock might be a new treatment strategy in allergy and immunology. PMID- 26560039 TI - IL-25 and CD4(+) TH2 cells enhance type 2 innate lymphoid cell-derived IL-13 production, which promotes IgE-mediated experimental food allergy. AB - BACKGROUND: Food-mediated allergic reactions have emerged as a major health problem. The underlying mechanisms that promote uncontrolled type 2 immune responses to dietary allergens in the gastrointestinal tract remain elusive. OBJECTIVE: We investigated whether altering IL-25 signaling enhances or attenuates allergic responses to food allergens. METHODS: Mice of an IL-25 transgenic mouse line (iIL-25Tg mice), which constitutively overexpress intestinal IL-25, and Il17rb(-/-) mice, in which Il17rb gene expression is disrupted, were sensitized and gavage fed with ovalbumin (OVA). We assessed symptomatic characteristics of experimental food allergy, including incidence of diarrhea, incidence of hypothermia, intestinal TH2 immune response, and serum OVA specific IgE and mast cell protease 1 production. RESULTS: Rapid induction of Il25 expression in the intestinal epithelium preceded onset of the anaphylactic response to ingested OVA antigen. iIL-25Tg mice were more prone and Il17rb(-/-) mice were more resistant to experimental food allergy. Resident intestinal type 2 innate lymphoid cells (ILC2s) were identified as the major producers of IL-5 and IL-13 in response to IL-25. Reconstituting irradiated wild-type mice with Rora(-/ ) or Il17rb(-/-) bone marrow resulted in a deficiency or dysfunction of the ILC2 compartment, respectively, and resistance to experimental food allergy. Repeated intragastric antigen challenge induced a significant increase in numbers of CD4(+) TH2 cells, which enhance IL-25-stimulated IL-13 production by ILC2s ex vivo and in vivo. Finally, reconstituted IL-13-deficient ILC2s had reduced capability to promote allergic inflammation, resulting in increased resistance to experimental food allergy. CONCLUSION: IL-25 and CD4(+) TH2 cells induced by ingested antigens enhance ILC2-derived IL-13 production, thereby promoting IgE mediated experimental food allergy. PMID- 26560040 TI - Low E-prostanoid 2 receptor levels and deficient induction of the IL-1beta/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin exacerbated respiratory disease. AB - BACKGROUND: We hypothesized that the 2 reported alterations in aspirin exacerbated respiratory disease (AERD), reduced expression/production of COX 2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked. OBJECTIVE: We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD. METHODS: Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8). Expression of the autocrine loop components regulating PGE2 production and signaling, namely IL-1 type I receptor (IL-1RI), COX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and after stimulation with IL-1beta, PGE2, and specific EP receptor agonists. RESULTS: Compared with NM-C fibroblasts, basal expression levels of IL-1RI and EP2 receptor were lower in NP-AERD fibroblasts. IL-1beta induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells. Levels of IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts. Incubation with either exogenous PGE2 or selective EP2 agonist significantly increased expression of IL-1RI in NM-C fibroblasts and had hardly any effect on NP-AERD fibroblasts. Alterations in IL 1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblasts were corrected when EP2 receptor expression was normalized by transfection of NP-AERD fibroblasts. CONCLUSION: Altered expression of EP2 in patients with AERD contributes to deficient induction of IL-1RI, reducing the capacity of IL-1beta to increase COX-2 and mPGES-1 expression, which results in low PGE2 production. This impairment in the generation of PGE2 subsequently reduces its ability to induce IL-1RI. PMID- 26560041 TI - A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency. PMID- 26560042 TI - Antigen-presenting epithelial cells can play a pivotal role in airway allergy. PMID- 26560043 TI - Tissue proteases convert CCL23 into potent monocyte chemoattractants in patients with chronic rhinosinusitis. PMID- 26560044 TI - GM-CSF treatment prevents respiratory syncytial virus-induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation. AB - BACKGROUND: Human respiratory syncytial virus (RSV) is a frequent cause of asthma exacerbations, yet the susceptibility of asthmatic patients to RSV is poorly understood. OBJECTIVE: We sought to address the contribution of resident alveolar macrophages (rAMs) to susceptibility to RSV infection in mice that recovered from allergic airway eosinophilia. METHODS: Mice were infected with RSV virus after clearance of allergic airway inflammation (AAI). The contribution of post-AAI rAMs was studied in vivo by means of clodronate liposome-mediated depletion, adoptive transfer, and treatment with recombinant cytokines before RSV infection. RESULTS: After clearing the allergic bronchial inflammation, post-AAI mice had bronchial hyperreactivity and increased inflammatory cell influx when infected with RSV compared with nonallergic mice, whereas viral clearance was comparable in both mouse groups. Post-AAI rAMs were necessary and sufficient for mediating these proinflammatory effects. In post-AAI mice the residing CD11c(hi) autofluorescent rAM population did not upregulate the terminal differentiation marker sialic acid-binding immunoglobulin-like lectin F and overproduced TNF and IL-6 through increased nuclear factor kappaB nuclear translocation. In line with these results, post-AAI lungs had reduced levels of the rAM maturation cytokine GM-CSF. Intratracheal administration of GM-CSF induced final rAM maturation in post-AAI mice and prevented the increased susceptibility to RSV-induced hyperreactivity and inflammation. CONCLUSION: Defective production of GM-CSF leads to insufficient post-AAI rAM maturation in mice that recovered from an AAI, causing increased susceptibility to RSV-induced immunopathology. Promoting the differentiation of post-AAI rAMs might be a therapeutic option for preventing RSV induced exacerbations in human asthmatic patients. PMID- 26560045 TI - Efficacy of T-cell transcription factor-specific DNAzymes in murine skin inflammation models. PMID- 26560046 TI - GSK3beta mediates the carcinogenic effect of HPV16 in cervical cancer. AB - Cervical cancer is one of the most prevalent and fatal cancers among women and infection of the human papillomavirus (HPV) is the most important risk factor. This study investigated how HPV16 regulated GSK3beta expression and function to promote cervical cancers. The expression of GSK3beta was analyzed by quantitative PCR and western blot. The proliferation, invasion, and clonogenic survival of cells with different E6/E7 levels were measured by MTT, transwell invasion assays, and soft agar colony-forming assays, respectively. The levels of GSK3beta were correlated with the copy numbers and expression levels of HPV16 E6/E7 genes. HPV16 E6/E7 genes regulated GSK3beta transcription through an element located in the promoter 85 and 250 base pairs upstream of the transcription start site. The abilities of cell proliferation, invasion, and clonogenic survival were increased in C33A cells by ectopic HPV16 E6/E7 and decreased in CaSki cells by knocking down HPV16 E6/E7 levels. Meanwhile, LiCl increased GSK3beta transcript levels and the proliferation of CaSki cells in a HPV16-dependent manner. These data indicated that GSK3beta may participated in HPV16 mediated deregulation of wnt/beta-catenin and other signaling pathways promoting the progression and invasion of cervical cancers. PMID- 26560047 TI - Pan-transcriptomic analysis identifies coordinated and orthologous functional modules in the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum. AB - Diatoms are important primary producers in the ocean that thrive in diverse and dynamic environments. Their survival and success over changing conditions depend on the complex coordination of gene regulatory processes. Here we present an integrated analysis of all publicly available microarray data for the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum. This resource includes shared expression patterns, gene functions, and cis-regulatory DNA sequence motifs in each species that are statistically coordinated over many experiments. These data illustrate the coordination of transcriptional responses in diatoms over changing environmental conditions. Responses to silicic acid depletion segregate into multiple distinctly regulated groups of genes, regulation by heat shock transcription factors (HSFs) is implicated in the response to nitrate stress, and distinctly coordinated carbon concentrating, CO2 and pH-related responses are apparent. Fundamental features of diatom physiology are similarly coordinated between two distantly related diatom species, including the regulation of photosynthesis, cellular growth functions and lipid metabolism. These integrated data and analyses can be explored publicly (http://networks.systemsbiology.net/diatom-portal/). PMID- 26560048 TI - Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship. AB - The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM. P-gp induction is one of the recently targeted strategy to increase amyloid-beta clearance from Alzheimer brains. Thus, we pursued a medicinal chemistry of fascaplysin to establish its structure-activity relationship for P-gp induction activity. Four series of analogs viz. substituted quaternary fascaplysin analogs, D-ring opened quaternary analogs, D-ring opened non-quaternary analogs, and beta-carbolinium analogs were synthesized and screened for P-gp induction activity. Among the total of 48 analogs screened, only quaternary nitrogen containing analogs 6a-g and 10a, 10h-l displayed promising P-gp induction activity; whereas non-planar non-quaternary analogs 9a-m, 13a-n, 15a-h were devoid of this activity. The P-gp induction activity of best compounds was then confirmed by western-blot analysis, which indicated that fascaplysin (6a) along with 4,5-difluoro analog of fascaplysin 6f and D-ring opened analog 10j displayed 4-8 fold increase in P-gp expression in LS-180 cells at 1 MUM. Additionally, compounds 6a and 6f also showed inhibition of acetylcholinestease (AChE), an enzyme responsible for neuronal loss in Alzheimer's disease. Thus, fascaplysin and its analogs showing promising P-gp induction along with AChE inhibition at 1 MUM, with good safety window (LS-180: IC50 > 10 MUM, hGF: 4 MUM), clearly indicates their promise for development as an anti-Alzheimer agent. PMID- 26560049 TI - Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents. AB - Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7 g, 7 m, 7 o, 8 e, 8 g, and 8 m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8 g exhibited the strongest activity. In particular, compound 8 g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8 g may be a potent antitumor agent, representing a promising lead for further optimization. PMID- 26560050 TI - Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols. AB - Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock--MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as RM0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3 phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 A--from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 A--from the phenyl ring to the amide group, and 3.112 A--from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). PMID- 26560051 TI - Cutaneous Lymphoma in Korea: A Nationwide Retrospective Study. AB - The epidemiological and clinicopathological features of cutaneous lymphoma may vary by geographical area. However, only a few large-scale epidemiological studies of cutaneous lymphoma have been performed, mainly in the USA and Europe. This aim of this study was to determine the recent characteristics of cutaneous lymphoma in Korea according to the WHO/EORTC classification. A total of 422 patients with newly diagnosed cutaneous lymphoma from January 2009 to December 2013 comprising 293 cases of mature T-cell and natural killer (NK)-cell lymphoma and 39 cases of mature B-cell lymphoma were retrospectively reviewed. The incidence of mature B-cell lymphoma was lower in Korea than in Europe and the USA. Diffuse large B-cell lymphoma was more prevalent in Korea than in Western countries. The incidence of extranodal NK/T-cell lymphoma, nasal-type was higher in Korea than in Western countries and Japan. PMID- 26560052 TI - Longitudinal assessment of hepatitis C fibrosis progression by collagen and smooth muscle actin morphometry in comparison to serum markers. AB - BACKGROUND: Assessment of fibrosis progression in chronic liver disease relies upon non-invasive tools and changes in semi-quantitative histopathology scores that may not be reliable. AIM: To assess the diagnostic performance of the FibroSURE (FS) index and collagen/alpha smooth muscle actin (alpha-SMA) morphometry in relation to longitudinal changes in fibrosis on paired biopsies. METHODS: The study cohort included 201 chronic hepatitis C (CHC) nonresponders enrolled in a prior phase II anti-fibrotic study. Serum FS and paired biopsies, with both collagen and alpha-SMA morphometry, were evaluated at baseline and week 52. RESULTS: Study patients were mostly male (67%) and Caucasian (77%), with Ishak stages 2 (n = 79), 3 (n = 88) and 4 (n = 30), excluded (n = 4 stage 1 or 5). Mean biopsy length was 22.9 mm. For baseline Ishak 2/3 vs. 4, there were no significant differences in AUROCs for collagen (0.71), SMA (0.66) or FS (0.70). At week 52, 62% of patients had no change in Ishak stage, but collagen/alpha-SMA increased by 34-51% (P < 0.0001), and FS decreased by 5% (P = 0.008). Among the 33% of patients with +/-1 Ishak stage change, FS changes were not significant, but alpha-SMA increased 29-72%, and collagen increased by 12-38% (P = 0.01 for +1 only). CONCLUSIONS: Longitudinal changes in collagen and alpha-SMA morphometry are apparent prior to change in histological stage or FibroSURE in CHC nonresponders with intermediate fibrosis. This likely reflects quantitative morphological differences that are not detected by routine histological staging or serum markers such as FibroSURE. PMID- 26560053 TI - Treatment of Acrodermatitis Continua of Hallopeau With Ustekinumab as Monotherapy. PMID- 26560054 TI - Current status of chimeric antigen receptor therapy for haematological malignancies. AB - The field of adoptive cell transfer includes chimeric antigen receptor (CAR) engineered T cells, constructs that emerged from basic research into principles of immunology and have transformed into clinically effective therapies for haematological malignancies. T cells engineered to express these artificial receptors hold great promise, but also carry significant risk. While permanent genetic modification of mature T cells appears safe, modulating their in vivo function is difficult, partly because the robust response can trigger other arms of the immune system. Suicide systems and toxicity management with cytokine blockade or signal transduction modulators have emerged as a new frontier in this field, a far cry from early problems getting CAR T cells to work at all. Currently, clinical trials in patients with relapsed or refractory B cell malignancies treated with CD19-specific CAR T cells have induced durable remissions in adults and children. Results from these trials indicate that more work needs to be done to understand biomarkers of efficacy, the role of T cell persistence and how to integrate this care into standard practice. Cell therapy will not be a 'one size fits all' class of medicine, and here we will discuss the development of this therapy and important questions for its future. PMID- 26560055 TI - Self-rated chronic conditions and 2-week prevalence in adults in Zhongshan, China: an epidemiological survey. AB - OBJECTIVE: To examine the association between behavioural factors and the risk of chronic conditions and 2-week prevalence. DESIGN: This was a cross-sectional survey. SETTING: The study was conducted in Zhongshan, China. PARTICIPANTS: A multistage clustering sampling method was used to select a representative sample of residents from the household registration system between July and September 2011. The overall sample replacement rate was 9.4%, and the final sample included 43 028 individuals. OUTCOME MEASURES: Chronic conditions and 2-week prevalence. RESULTS: 4979 (11.6%) of the participants reported having at least one chronic condition, 1067 (2.5%) had two or more concurrent chronic conditions, and 6830 (15.9%) reported having at least one disease in a 2-week recall period. The most common chronic condition was primary hypertension, which was reported by 6.8% of participants. Logistic regression models demonstrated that the main factors for having a chronic condition and 2-week prevalence were older age (>=65 years of age; OR 44.91, 95% CI 33.05 to 61.03; and OR 12.71, 95% CI 10.44 to 15.46, respectively), obesity (OR 3.00, 95% CI 2.63 to 3.42; and OR 2.50, 95% CI 2.22 to 2.82, respectively) and being a former smoker (OR 3.02, 95% CI 2.54 to 3.58; and OR 3.24, 95% CI 2.74 to 3.82, respectively). CONCLUSIONS: This study suggests that older age, obesity and unhealthy behaviours are high-risk factors for poorer health status among the residents of Zhongshan, China. The present findings highlight the importance of recognising and managing harmful behaviours in order to improve health. PMID- 26560056 TI - Evidence used in model-based economic evaluations for evaluating pharmacogenetic and pharmacogenomic tests: a systematic review protocol. AB - INTRODUCTION: Decision models can be used to conduct economic evaluations of new pharmacogenetic and pharmacogenomic tests to ensure they offer value for money to healthcare systems. These models require a great deal of evidence, yet research suggests the evidence used is diverse and of uncertain quality. By conducting a systematic review, we aim to investigate the test-related evidence used to inform decision models developed for the economic evaluation of genetic tests. METHODS AND ANALYSIS: We will search electronic databases including MEDLINE, EMBASE and NHS EEDs to identify model-based economic evaluations of pharmacogenetic and pharmacogenomic tests. The search will not be limited by language or date. Title and abstract screening will be conducted independently by 2 reviewers, with screening of full texts and data extraction conducted by 1 reviewer, and checked by another. Characteristics of the decision problem, the decision model and the test evidence used to inform the model will be extracted. Specifically, we will identify the reported evidence sources for the test-related evidence used, describe the study design and how the evidence was identified. A checklist developed specifically for decision analytic models will be used to critically appraise the models described in these studies. Variations in the test evidence used in the decision models will be explored across the included studies, and we will identify gaps in the evidence in terms of both quantity and quality. DISSEMINATION: The findings of this work will be disseminated via a peer-reviewed journal publication and at national and international conferences. PMID- 26560057 TI - Testing a model of facilitated reflection on network feedback: a mixed method study on integration of rural mental healthcare services for older people. AB - OBJECTIVE: To test a management model of facilitated reflection on network feedback as a means to engage services in problem solving the delivery of integrated primary mental healthcare to older people. DESIGN: Participatory mixed methods case study evaluating the impact of a network management model using organisational network feedback (through social network analysis, key informant interviews and policy review). INTERVENTION: A model of facilitated network reflection using network theory and methods. SETTING: A rural community in South Australia. PARTICIPANTS: 32 staff from 24 services and 12 senior service managers from mental health, primary care and social care services. RESULTS: Health and social care organisations identified that they operated in clustered self-managed networks within sectors, with no overarching purposive older people's mental healthcare network. The model of facilitated reflection revealed service goal and role conflicts. These discussions helped local services to identify as a network, and begin the problem-solving communication and referral links. A Governance Group assisted this process. Barriers to integrated servicing through a network included service funding tied to performance of direct care tasks and the lack of a clear lead network administration organisation. CONCLUSIONS: A model of facilitated reflection helped organisations to identify as a network, but revealed sensitivity about organisational roles and goals, which demonstrated that conflict should be expected. Networked servicing needed a neutral network administration organisation with cross-sectoral credibility, a mandate and the resources to monitor the network, to deal with conflict, negotiate commitment among the service managers, and provide opportunities for different sectors to meet and problem solve. This requires consistency and sustained intersectoral policies that include strategies and funding to facilitate and maintain health and social care networks in rural communities. PMID- 26560058 TI - A multilevel study on the association of observer-assessed working conditions with depressive symptoms among female eldercare workers from 56 work units in 10 care homes in Denmark. AB - OBJECTIVES: Eldercare workers in Denmark have a higher prevalence of poor psychological health than other occupational groups. We examined the association between working conditions assessed by trained observers and depressive symptoms assessed by self-report in a study of female Danish eldercare workers. METHODS: Working conditions were observed based on action regulation theory and defined as (1) regulation requirements, a workplace resource providing opportunity for decision-making and skill development and (2) barriers for task completion. We examined the associations of individual and work unit averaged working conditions with depressive symptoms in a sample of 95 individually observed eldercare workers. Further, we examined the association of work unit averaged working conditions with depressive symptoms in a sample of 205 care workers, including both observed and non-observed individuals. We used regression models that allowed for correlations within work units and care homes and adjusted these models for demographics, job characteristics and stressful life events. RESULTS: Higher levels of regulation requirements were associated with lower depressive symptoms at the individual level (p=0.04), but not at the workplace level. Barriers were not associated with depressive symptoms at the individual level. At the workplace level, a higher number of qualitatively different barriers (p=0.04) and a higher number of barriers for equipment use (p=0.03) were associated with lower levels of depressive symptoms in the age and cohabitation adjusted model, however statistical significance was lost in the fully adjusted model. CONCLUSIONS: Low level of regulation requirements was associated with a high level of depressive symptoms. The study highlights the importance of examining both individual and workplace levels of working conditions. PMID- 26560059 TI - Defining venous thromboembolism and measuring its incidence using Swedish health registries: a nationwide pregnancy cohort study. AB - OBJECTIVE: To accurately define venous thromboembolism (VTE) in the routinely collected Swedish health registers and quantify its incidence in and around pregnancy. STUDY DESIGN: Cohort study using data from the Swedish Medical Birth Registry (MBR) linked to the National Patient Registry (NPR) and the Swedish Prescribed Drug Register (PDR). SETTING: Secondary care centres, Sweden. PARTICIPANT: 509,198 women aged 15-44 years who had one or more pregnancies resulting in a live birth or stillbirth between 2005 and 2011. MAIN OUTCOME MEASURE: To estimate the incidence rate (IR) of VTE in and around pregnancy using various VTE definitions allowing direct comparison with other countries. RESULTS: The rate of VTE varied based on the VTE definition. We found that 43% of cases first recorded as outpatient were not accompanied by anticoagulant prescriptions, whereas this proportion was much lower than those cases first recorded in the inpatient register (9%). Using our most inclusive VTE definition, we observed higher rates of VTE compared with previously published data using similar methodology. These reduced by 31% (IR=142/100,000 person-years; 95% CI 132 to 153) and 22% (IR=331/100,000 person-years; 95% CI 304 to 361) during the antepartum and postpartum periods, respectively, using a restrictive VTE definition that required anticoagulant prescriptions associated with diagnosis, which were more in line with the existing literature. CONCLUSIONS: We found that including VTE codes without treatment confirmation risks the inclusion of false positive cases. When defining VTE using the NPR, anticoagulant prescription information should therefore be considered particularly for cases recorded in an outpatient setting. PMID- 26560060 TI - Patient and nurse preferences for nurse handover-using preferences to inform policy: a discrete choice experiment protocol. AB - INTRODUCTION: Nursing bedside handover in hospital has been identified as an opportunity to involve patients and promote patient-centred care. It is important to consider the preferences of both patients and nurses when implementing bedside handover to maximise the successful uptake of this policy. We outline a study which aims to (1) identify, compare and contrast the preferences for various aspects of handover common to nurses and patients while accounting for other factors, such as the time constraints of nurses that may influence these preferences.; (2) identify opportunities for nurses to better involve patients in bedside handover and (3) identify patient and nurse preferences that may challenge the full implementation of bedside handover in the acute medical setting. METHODS AND ANALYSIS: We outline the protocol for a discrete choice experiment (DCE) which uses a survey design common to both patients and nurses. We describe the qualitative and pilot work undertaken to design the DCE. We use a D-efficient design which is informed by prior coefficients collected during the pilot phase. We also discuss the face-to-face administration of this survey in a population of acutely unwell, hospitalised patients and describe how data collection challenges have been informed by our pilot phase. Mixed multinomial logit regression analysis will be used to estimate the final results. ETHICS AND DISSEMINATION: This study has been approved by a university ethics committee as well as two participating hospital ethics committees. Results will be used within a knowledge translation framework to inform any strategies that can be used by nursing staff to improve the uptake of bedside handover. Results will also be disseminated via peer-reviewed journal articles and will be presented at national and international conferences. PMID- 26560061 TI - Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review. AB - INTRODUCTION: In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, 'domains') are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, 'what') is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process. METHODS AND ANALYSIS: Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. TRIAL REGISTRATION NUMBER: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. PMID- 26560062 TI - Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns. AB - OBJECTIVE: Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. METHODS: We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. RESULTS: Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. CONCLUSIONS: Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. PMID- 26560063 TI - Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study. AB - OBJECTIVE: POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome. METHOD: This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival. RESULTS: Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months. CONCLUSIONS: Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials. PMID- 26560064 TI - Effect of vegetable consumption on the association between peripheral leucocyte telomere length and hypertension: a case-control study. AB - OBJECTIVES: Peripheral leucocyte telomere length has been suggested to be inversely associated with hypertension risk. Both telomere length and hypertension risk can be modified by certain dietary factors, such as fruit and vegetables. This study was to examine the potential effect of these dietary factors on the association between telomere length and hypertension risk. STUDY DESIGN: A community-based case-control study. PARTICIPANTS: 271 hypertensive patients and 455 normotensive controls aged 40-70 years and living in Yinzhou, Zhejiang Province, China. OUTCOME MEASURES: Peripheral leucocyte relative telomere length (RTL) was measured using quantitative real-time PCR. Dietary intake was assessed by a brief semiquantitative food frequency questionnaire. The association between RTL and hypertension risk was analysed using logistic regression, and the modulatory effect of dietary intake on RTL-related hypertension risk was analysed using likelihood ratio tests. RESULTS: Among controls, longer age-adjusted RTL was associated with higher vegetable intake (p=0.01). Individuals with longer age-adjusted RTL (based on median value) were 30% less likely to have hypertension (OR=0.70, 95% CI 0.52 to 0.96; p=0.03). The observed RTL-hypertension relationship appeared to be modified by vegetable intake-longer RTL was significantly associated with lower hypertension risk only in those with greater vegetable consumption (OR=0.28, 95% CI 0.14 to 0.57; p<0.001), but not in those with lower vegetable intake (P-interaction=0.008). CONCLUSIONS: Certain dietary factors might modify telomere-related hypertension risk. PMID- 26560065 TI - Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication. AB - Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under nonoptimal culture conditions but also provide valuable insights into intriguing biological principles, including the balance of proteome resource allocation and the role of gene duplication in evolutionary history. PMID- 26560066 TI - Integrated Transcriptomic-Proteomic Analysis Using a Proteogenomic Workflow Refines Rat Genome Annotation. AB - Proteogenomic re-annotation and mRNA splicing information can lead to the discovery of various protein forms for eukaryotic model organisms like rat. However, detection of novel proteoforms using mass spectrometry proteomics data remains a formidable challenge. We developed EuGenoSuite, an open source multiple algorithmic proteomic search tool and utilized it in our in-house integrated transcriptomic-proteomic pipeline to facilitate automated proteogenomic analysis. Using four proteogenomic pipelines (integrated transcriptomic-proteomic, Peppy, Enosi, and ProteoAnnotator) on publicly available RNA-sequence and MS proteomics data, we discovered 363 novel peptides in rat brain microglia representing novel proteoforms for 249 gene loci in the rat genome. These novel peptides aided in the discovery of novel exons, translation of annotated untranslated regions, pseudogenes, and splice variants for various loci; many of which have known disease associations, including neurological disorders like schizophrenia, amyotrophic lateral sclerosis, etc. Novel isoforms were also discovered for genes implicated in cardiovascular diseases and breast cancer for which rats are considered model organisms. Our integrative multi-omics data analysis not only enables the discovery of new proteoforms but also generates an improved reference for human disease studies in the rat model. PMID- 26560067 TI - Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin associated Protein Complexes Using Single Affinity Purification. AB - In recent years, cross-linking mass spectrometry has proven to be a robust and effective method of interrogating macromolecular protein complex topologies at peptide resolution. Traditionally, cross-linking mass spectrometry workflows have utilized homogenous complexes obtained through time-limiting reconstitution, tandem affinity purification, and conventional chromatography workflows. Here, we present cross-linking immunoprecipitation-MS (xIP-MS), a simple, rapid, and efficient method for structurally probing chromatin-associated protein complexes using small volumes of mammalian whole cell lysates, single affinity purification, and on-bead cross-linking followed by LC-MS/MS analysis. We first benchmarked xIP-MS using the structurally well-characterized phosphoribosyl pyrophosphate synthetase complex. We then applied xIP-MS to the chromatin associated cohesin (SMC1A/3), XRCC5/6 (Ku70/86), and MCM complexes, and we provide novel structural and biological insights into their architectures and molecular function. Of note, we use xIP-MS to perform topological studies under cell cycle perturbations, showing that the xIP-MS protocol is sufficiently straightforward and efficient to allow comparative cross-linking experiments. This work, therefore, demonstrates that xIP-MS is a robust, flexible, and widely applicable methodology for interrogating chromatin-associated protein complex architectures. PMID- 26560069 TI - Estimation of Drug Binding to Brain Tissue: Methodology and in Vivo Application of a Distribution Assay in Brain Polar Lipids. AB - The unbound drug concentration-effect relationship in brain is a key aspect in CNS drug discovery and development. In this work, we describe an in vitro high throughput distribution assay between an aqueous buffer and a microemulsion of porcine brain polar lipids (BPL). The derived distribution coefficient LogDBPL was applied to the prediction of unbound drug concentrations in brain (Cu,b) and nonspecific binding to brain tissue. The in vivo relevance of the new assay was assessed for a large set of proprietary drug candidates and CNS drugs by (1) comparing observed compound concentrations in rat CSF with Cu,b calculated using the LogDBPL assay in combination with total drug brain concentrations, (2) comparing Cu,b derived from LogDBPL and total drug brain concentrations to Cu,b estimated using in vitro P-glycoprotein efflux ratio data and unbound drug plasma levels, and (3) comparing tissue nonspecific binding data from human brain autoradiography studies for 17 PET tracer candidates to distribution in BPL. In summary, the LogDBPL assay provides a predicted drug fraction unbound in brain tissue that is nearly identical to brain homogenate equilibrium dialysis with an estimation of in vivo Cu,b that is superior to LogD in octanol. LogDBPL complements the approach for predicting Cu,b based on in vitro P-glycoprotein efflux ratio and in vivo unbound plasma concentration and stands as a fast and cost-effective tool for nonspecific brain binding optimization of PET ligand candidates. PMID- 26560068 TI - Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling. AB - Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. However, the integrated proteomic response of human endothelial cells to R. conorii infection is not known. In this study, we performed quantitative proteomic profiling of primary human umbilical vein endothelial cells (HUVECs) with established R conorii infection versus those stimulated with endotoxin (LPS) alone. We observed differential expression of 55 proteins in HUVEC whole cell lysates. Of these, we observed induction of signal transducer and activator of transcription (STAT)1, MX dynamin-like GTPase (MX1), and ISG15 ubiquitin-like modifier, indicating activation of the JAK-STAT signaling pathway occurs in R. conorii-infected HUVECs. The down-regulated proteins included those involved in the pyrimidine and arginine biosynthetic pathways. A highly specific biotinylated cross-linking enrichment protocol was performed to identify dysregulation of 11 integral plasma membrane proteins that included up-regulated expression of a sodium/potassium transporter and down-regulation of alpha-actin 1. Analysis of Golgi and soluble Golgi fractions identified up-regulated proteins involved in platelet-endothelial adhesion, phospholipase activity, and IFN activity. Thirty four rickettsial proteins were identified with high confidence in the Golgi, plasma membrane, or secreted protein fractions. The host proteins associated with rickettsial infections indicate activation of interferon-STAT signaling pathways; the disruption of cellular adhesion and alteration of antigen presentation pathways in response to rickettsial infections are distinct from those produced by nonspecific LPS stimulation. These patterns of differentially expressed proteins suggest mechanisms of pathogenesis as well as methods for diagnosis and monitoring Rickettsia infections. PMID- 26560070 TI - Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation. AB - AIM: Mutations of LMX1B cause nail-patella syndrome, a rare autosomal dominant disorder. Recently, LMX1B R246Q heterozygous mutations were recognised in nephropathy without extrarenal manifestation. The aim of this study was to clarify characteristics of nephropathy caused by R246Q mutation. METHODS: Whole exome sequencing was performed on a large family with nonsyndromic autosomal dominant nephropathy without extrarenal manifestation. Clinical and histological findings of patients with LMX1B mutation were investigated. RESULTS: LMX1B R246Q heterozygous mutation was identified in five patients over three generations. Proteinuria or haematoproteinuria was recognized by urinary screening from all patients in childhood. Proteinuria gradually increased to nephrotic levels and renal function decreased in adolescence. Two patients progressed to end-stage renal disease in adulthood. Renal histology demonstrated minimal change in childhood and focal segmental glomerulosclerosis in adulthood. Using electron microscopy, focal collagen deposition could be detected in glomeruli even when a "moth-eaten appearance" was not apparent in the glomerular basement membrane. In addition, podocin expression in glomerular podocytes was significantly decreased, even in the early stages of disease progression. CONCLUSION: Comprehensive genetic analyses and collagen or tannic acid staining may be useful for diagnosis of LMX1B-associated nephropathy. While renal prognosis of R246Q may be worse than that of typical NPS nephropathy, signs of podocytopathy can be detected during the infantile period; thus, childhood urinary screening may facilitate early detection. PMID- 26560071 TI - Effects of dietary supplementation of selenium and iodine on growth performance, carcass characteristics and histology of thyroid gland in goats. AB - This study assessed the effects of dietary selenium (Se), iodine (I) and a combination of both on growth performance, thyroid gland activity, carcass characteristics and the concentration of iodine and selenium in Longissimus lumborum (LL) muscle in goats. Twenty-four bucks were randomly assigned to four dietary treatments: control (CON), basal diet without supplementation, basal diet + 0.6 mg Se/kg dry matter (DM) (SS), 0.6 mg I/kg DM (IP), or combination of 0.6 mg/kg DM Se and 0.6 mg/kg DM I (SSIP) and fed for 100 days. Animals fed diet SSIP exhibited higher (P < 0.05) body weight and better feed conversion ratio (FCR) than those fed other diets. Dressing percentage of goats fed the supplemented diets was higher (P < 0.05) than that of the control. Carcasses from the IP group had higher (P < 0.05) total fat proportion than the SSIP group. The levels of both elements were significantly elevated (P < 0.05) in LL muscle in supplemented goats. Thyroid follicular epithelial cells of IP and SSIP animals were significantly higher than those of CON and SS groups. The study demonstrated that the combined Se and I dietary supplementation improves growth performance, carcass dressing percentage and increases the retention of Se and I in goat meat. PMID- 26560072 TI - Winter cropping in Ficus tinctoria: an alternative strategy. AB - The many species of figs (Ficus, Moraceae) have evolved a variety of reproductive phenologies that ensure the survival of both the fig plants and their short lived, species-specific, pollinating wasps. A phenological study of 28 male and 23 female plants of a dioecious hemiepiphytic fig, Ficus tinctoria, was conducted in Xishuangbanna, SW China at the northern margin of tropical SE Asia. In contrast to other figs of seasonal climates, which have a winter low in fig production, both sexes produced their major fig crops at the coldest time of the year. Male plants released pollinators during the period when most female trees were receptive and male syconia had a long wasp-producing (D) phase, which ensured high levels of pollination. Female crops ripened at the end of the dry season, when they attracted numerous frugivorous birds and dispersed seeds can germinate with the first reliable rains. Few syconia were produced by either sex during the rest of the year, but these were sufficient to maintain local pollinator populations. We suggest that this unique phenological strategy has evolved to maximize seed dispersal and establishment in this seasonal climate. PMID- 26560073 TI - Endoscope-guided coblator tongue base resection using an endoscope-holding system for obstructive sleep apnea. AB - BACKGROUND: Multilevel obstruction in obstructive sleep apnea commonly includes retroglossal obstruction. To improve surgical success rates, tongue volume reduction with posterior midline glossectomy and/or lingual tonsillectomy is widely performed. METHODS: Nasotracheal intubation was utilized, and the combined tongue procedure was performed as a final step after palatal surgery. The tongue was pulled maximally by a retraction suture and a McIVOR (Karl Storz, Tuttlingen, Germany) or Davis mouth gag (Karl Storz,Tuttlingen, Germany), and a medium-length tongue blade was applied to expose the tongue base. A 70-degree rigid endoscope was fixed by the holding system and introduced into the oral cavity. Endoscope guided coblator tongue base resection was then performed. RESULTS: The surgeon could use both hands for the surgery, enabling a more delicate resection of tongue base tissue. CONCLUSION: This technique was acceptable and can be successfully used in patients with a large tongue, in whom exposing the tongue base for surgery is difficult. PMID- 26560075 TI - The Impact of Posttraumatic Stress Disorder on Physiological Arousal, Disability, and Sensory Pain Thresholds in Patients With Chronic Whiplash. AB - OBJECTIVE: Whiplash-associated disorders (WAD) are common and incur substantial personal and economic costs. Research has shown that persistent posttraumatic stress reactions predict poorer functional recovery in WAD; however, the specific mechanism through which this occurs is unclear. The current study is the first to examine the direct impact of posttraumatic stress disorder (PTSD) symptoms in WAD using laboratory tested pain measures. MATERIALS AND METHODS: A mixed experimental design was used to examine the impact of exposure to accident cues on chronic WAD individuals with (n=33) and without (n=39) PTSD. Groups were compared at baseline and postaccident cue on self-reported pain and negative effect and laboratory tested arousal and sensory pain threshold measures. RESULTS: At baseline, WAD individuals with PTSD reported greater disability, negative effect, pain, arousal, and lower pain thresholds than those without PTSD. As expected, exposure to accident cues resulted in greater increases in arousal and negative effect for those with PTSD. Changes in sensory pain thresholds revealed a hyperalgesic effect in cold pain thresholds for the PTSD group compared with the No PTSD group and mixed findings for pressure pain thresholds. DISCUSSION: Findings from the current study highlight the negative impact of PTSD on both physical and psychological outcomes in chronic WAD. From a clinical perspective, data suggest that patients exposed to accident cues may experience arousal that lowers their threshold to certain pain stimuli. Further investigation of effective multidisciplinary interventions and in particular the treatment of PTSD in WAD is identified as an important area of further investigation. PMID- 26560074 TI - The anatomical basis for modulatory convergence in the antennal lobe of Manduca sexta. AB - The release of neuromodulators by widely projecting neurons often allows sensory systems to alter how they process information based on the physiological state of an animal. Neuromodulators alter network function by changing the biophysical properties of individual neurons and the synaptic efficacy with which individual neurons communicate. However, most, if not all, sensory networks receive multiple neuromodulatory inputs, and the mechanisms by which sensory networks integrate multiple modulatory inputs are not well understood. Here we characterized the relative glomerular distribution of two extrinsic neuromodulators associated with distinct physiological states, serotonin (5-HT) and dopamine (DA), in the antennal lobe (AL) of the moth Manduca sexta. By using immunocytochemistry and mass dye fills, we characterized the innervation patterns of both 5-HT- and tyrosine hydroxylase-immunoreactive processes relative to each other, to olfactory receptor neurons (ORNs), to projection neurons (PNs), and to several subsets of local interneurons (LNs). 5-HT immunoreactivity had nearly complete overlap with PNs and LNs, yet no overlap with ORNs, suggesting that 5-HT may modulate PNs and LNs directly but not ORNs. TH immunoreactivity overlapped with PNs, LNs, and ORNs, suggesting that dopamine has the potential to modulate all three cell types. Furthermore, the branching density of each neuromodulator differed, with 5-HT exhibiting denser arborizations and TH-ir processes being sparser. Our results suggest that 5-HT and DA extrinsic neurons target partially overlapping glomerular regions, yet DA extends further into the region occupied by ORNs. PMID- 26560076 TI - Social identity, social networks and recovery capital in emerging adulthood: A pilot study. AB - BACKGROUND: It has been argued that recovery from substance dependence relies on a change in identity, with past research focused on 'personal identity'. This study assessed support for a social identity model of recovery in emerging adults through examining associations between social identity, social networks, recovery capital, and quality of life. METHODS: Twenty participants aged 18-21 in residential treatment for substance misuse were recruited from four specialist youth drug treatment services - three detoxification facilities and one psychosocial rehabilitation facility in Victoria, Australia. Participants completed a detailed social network interview exploring the substance use of groups in their social networks and measures of quality of life, recovery capital, and social identity. RESULTS: Lower group substance use was associated with higher recovery capital, stronger identification with non-using groups, and greater importance of non-using groups in the social network. Additionally, greater identification with and importance of non-using groups were associated with better environmental quality of life, whereas greater importance conferred on using groups was associated with reduced environmental quality of life. CONCLUSIONS: Support was found for the role of social identity processes in reported recovery capital and quality of life. Future research in larger, longitudinal samples is required to improve understanding of social identity processes during treatment and early recovery and its relationship to recovery stability. PMID- 26560077 TI - The influence of international medical electives on career preference for primary care and rural practice. AB - BACKGROUND: Previous studies have demonstrated a correlation between medical students who undertake international medical electives (IMEs) in resource poor settings and their reported career preference for primary care in underserved areas such as rural practice. This study examines whether a similar correlation exists in the Australian medical school context. METHODS: Data was extracted from the Medical Schools Outcomes Database (MSOD) of Australian medical students that completed commencing student and exit questionnaires between 2006 and 2011. Student responses were categorized according to preferred training program and preferred region of practice at commencement. The reported preferences at exit of students completing IMEs in low and middle income countries (LMIC) were compared to those completing electives in high income countries (HIC). RESULTS: The effect of elective experience for students expressing a preference for primary care at commencement was non-significant, with 40.32 % of LMIC and 42.11 % of HIC students maintaining a preference for primary care. Similarly there were no significant changes following LMIC electives for students expressing a preference for specialist training at commencement with 11.81 % of LMIC and 10.23 % of HIC students preferring primary care at exit. The effect of elective experience for students expressing a preference for rural practice at commencement was non significant, with 41.51 % of LMIC and 49.09 % of HIC students preferring rural practice at exit. Similarly there were no significant changes following LMIC electives for students expressing a preference for urban practice at commencement, with 7.84 % of LMIC and 6.70 % of HIC students preferring rural practice at exit. CONCLUSIONS: This study did not demonstrate an association between elective experience in resource poor settings and a preference for primary care or rural practice. This suggests that the previously observed correlation between LMIC electives and interest in primary care in disadvantaged communities is likely dependent on student and elective program characteristics and supports the need for further research and critical examination of elective programs at Australian medical schools. PMID- 26560079 TI - A General Strategy for the Discovery of Metabolic Pathways: d-Threitol, l Threitol, and Erythritol Utilization in Mycobacterium smegmatis. AB - We describe a general integrated bioinformatic and experimental strategy to discover the in vitro enzymatic activities and in vivo functions (metabolic pathways) of uncharacterized enzymes discovered in microbial genome projects using the ligand specificities of the solute binding proteins (SBPs) for ABC transporters. Using differential scanning fluorimetry, we determined that the SBP for an ABC transporter encoded by the genome of Mycobacterium smegmatis is stabilized by d-threitol. Using sequence similarity networks and genome neighborhood networks to guide selection of target proteins for pathway enzymes, we applied both in vitro and in vivo experimental approaches to discover novel pathways for catabolism of d-threitol, l-threitol, and erythritol. PMID- 26560080 TI - TcpM: a novel relaxase that mediates transfer of large conjugative plasmids from Clostridium perfringens. AB - Conjugative transfer of toxin and antibiotic resistance plasmids in Clostridium perfringens is mediated by the tcp conjugation locus. Surprisingly, neither a relaxase gene nor an origin of transfer (oriT) has been identified on these plasmids, which are typified by the 47 kb tetracycline resistance plasmid pCW3. The tcpM gene (previously called intP) encodes a potential tyrosine recombinase that was postulated to be an atypical relaxase. Mutagenesis and complementation studies showed that TcpM was required for wild-type transfer of pCW3 and that a tyrosine residue, Y259, was essential for TcpM activity, which was consistent with the need for a relaxase-mediated hydrophilic attack at the oriT site. Other catalytic residues conserved in tyrosine recombinases were not required for TcpM activity, suggesting that TcpM was not a site-specific recombinase. Mobilization studies led to the identification of the oriT site, which was located in the 391 bp intergenic region upstream of tcpM. The oriT site was localized to a 150 bp region, and gel mobility shift studies showed that TcpM could bind to this region. Based on these studies we postulate that conjugative transfer of pCW3 involves the atypical relaxase TcpM binding to and processing the oriT site to initiate plasmid transfer. PMID- 26560081 TI - Analytical detection of trimetazidine produced by metabolic conversion of lomerizine in doping control analysis. AB - The identification of trimetazidine in urine samples might result from administration of the permitted drug lomerizine. Laboratories are therefore urged to carefully investigate suspicious cases where trimetazidine is detected. Differentiation of abuse of the banned substance trimetazidine from use of the permitted drug lomerizine would be supported by analysis of the intact drug lomerizine and/or specific metabolites. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26560078 TI - Serum irisin levels are lower in patients with breast cancer: association with disease diagnosis and tumor characteristics. AB - BACKGROUND: Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer. METHODS: Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated. RESULTS: Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 +/- 0.57 and 3.24 +/- 0.66 MUg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 MUg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively). CONCLUSIONS: Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease. PMID- 26560082 TI - Do We Need More Than a Transthoracic Echocardiography When Evaluating Children with Congenital Heart Disease before Cardiac Surgery? AB - AIM: To determine if a transthoracic echocardiography (TTE) can be used as the sole diagnostic imaging modality to evaluate children with congenital heart disease (CHD) undergoing cardiac surgery. METHODS: A retrospective study was carried out at the King Abdulaziz Cardiac Center. We reviewed all pediatric patients who underwent cardiac surgery during the period January 2011 to December 2011. RESULTS: Three hundred ninety-two pediatric patients with CHD fulfilled the inclusion criteria. Of these patients, 287 (73%) underwent surgical interventions based on a TTE alone, while 105 (27%) required additional diagnostic imaging modalities, including a cardiac catheterization (68/105; 65%), cardiac computed tomography angiography (36/105; 34%), or cardiac magnetic resonance imaging (1/105; 1%). A TTE was not enough for all the patients who underwent a cardiac catheterization to find out additional anatomical information (22%), either to directly measure pulmonary artery pressures (62%) or to study vascular reactivity in patients with pulmonary hypertension (16%). Of 36 patients who underwent a cardiac computed tomography angiography, five (14%) had additional information to be added to TTE findings. Of all the patients, 81% had enough information using only the TTE compared to 19% in whom the TTE was not enough to provide all needed information. Only (7/392; 1.8%) patients had additional minor intraoperative findings that did not affect the surgical decision. CONCLUSION: Despite the emergence of other imaging modalities, a TTE can be used as the sole diagnostic imaging modality for a preoperative assessment in the majority of children with CHD. Other imaging modalities can be employed with limited indications. PMID- 26560083 TI - Correction to "Concurrent Adaptation of Human and Machine Improves Simultaneous and Proportional Myoelectric Control". PMID- 26560084 TI - Correction to "Effects of Innovative WALKBOT Robotic-Assisted Locomotor Training on Balance and Gait Recovery in Hemiparetic Stroke: A Prospective, Randomized, Experimenter Blinded Case Control Study With a Four-Week Follow-Up". PMID- 26560085 TI - As-needed intravenous antihypertensive therapy and blood pressure control. AB - BACKGROUND: Hospitalized patients with elevated blood pressure (BP) in most cases should be treated with intensification of oral regimens, but are often given intravenous (IV) antihypertensives. OBJECTIVE: To determine frequency of prescribing and administering episodic IV antihypertensives and outcomes. DESIGN: Retrospective review. SETTING: Urban academic hospital. PATIENTS: Non-critically ill, hospitalized patients with an IV antihypertensive order for enalaprilat, labetalol, hydralazine, or metoprolol. MEASUREMENTS: We analyzed BP thresholds for ordering and administering IV antihypertensives, the types and frequencies of IV antihypertensives administered, and the effect of IV antihypertensive use on short-term BP and adverse outcomes. The BP change during hospitalization was contrasted in those receiving IV antihypertensives between those who did and did not receive subsequent intensification of chronic oral antihypertensive regimens. RESULTS: Two hundred forty-six patients had an episodic IV antihypertensive order. One hundred seventy-two patients received 458 doses, with 48% receiving a single dose. Over 98% of episodic IV antihypertensive doses were administered for systolic blood pressure (SBP) <200 mm Hg and 84.5% for SBP <180 mm Hg. Within 6 hours of administration, there was a statistically significant decline in average SBP and diastolic BP in patients receiving IV hydralazine and labetolol. After administration of IV antihypertensives, the oral inpatient medication regimen was adjusted in 52% of patients; these patients had a greater reduction in SBP from admission to discharge than patients with no change to their oral regimens. A total of 32.6% of patients receiving treatment experienced a BP reduction of more than 25% within 6 hours. CONCLUSIONS: IV antihypertensive drugs are ordered and administered in patients with asymptomatic, uncontrolled BP for levels unassociated with substantive immediate cardiovascular risk, which may cause adverse effects. PMID- 26560087 TI - Single circulating tumor cell sequencing as an advanced tool in cancer management. AB - Circulating tumor cells (CTCs) shed by the primary tumor and metastases are considered a real-time 'liquid biopsy', reflecting the disease complexity that evolves during progression, showing in its late stages different genetic, epigenetic and expression features. Consequently, heterogeneity and development of characteristic features upon disease progression are the two main goals that emerging technologies should account for in view of a clinical application. Single-cell analysis, now possible due to technological advances, may help elucidate tumor heterogeneity at the CTC level. This review focuses on the necessary steps for the analysis of CTCs at the single-cell level. A concise overview is given on the alternative methods referring in particular to studies on the mutational status of single CTCs from cancer patients. PMID- 26560086 TI - Central delivery of iodine-125-labeled cetuximab, etanercept and anakinra after perispinal injection in rats: possible implications for treating Alzheimer's disease. AB - INTRODUCTION: Alzheimer's disease is a debilitating condition, and the search for an effective treatment is ongoing. Inflammation, in reaction to amyloid deposition, is thought to accelerate cognitive decline. With tumor necrosis factor alpha being an important proinflammatory cytokine, a recent trial investigated the effect of the tumor necrosis factor alpha inhibitor etanercept after peripheral administration in patients with Alzheimer's disease. Although there was no significant effect, others have claimed spectacular effects of etanercept after perispinal injection. In the present study, the central delivery of drugs with a large molecular weight was evaluated after injection in the cervical perispinal region in rats. If successful, this strategy might increase therapeutic options for patients with Alzheimer's disease. METHODS: Nine male Sprague-Dawley rats were given injections of iodine-125-labeled cetuximab (146 kDa), etanercept (51 kDa), and anakinra (17 kDa). Each radioiodinated drug was injected in the perispinal region in two rats and into the dorsal tail vein in one rat. Directly after injection, the rats were placed in a head-down position for 3 minutes to direct blood flow into the valveless vertebral venous system. A single-positron emission computed tomography scan was acquired starting 5 minutes after injection, subsequently the rats were euthanized and bio-distribution was determined. RESULTS: Intracranial delivery of the radiolabeled drugs could not be visualized in all but one of the rats. Injected drugs accumulated locally in the perispinal region. CONCLUSIONS: In this study, no evidence could be found for the delivery of drugs to the central nervous system after perispinal injection. Additional research is needed before this treatment can be used in patients with Alzheimer's disease. PMID- 26560088 TI - PB2 subunit of avian influenza virus subtype H9N2: a pandemic risk factor. AB - Avian influenza viruses of subtype H9N2 that are found worldwide are occasionally transmitted to humans and pigs. Furthermore, by co-circulating with other influenza subtypes, they can generate new viruses with the potential to also cause zoonotic infections, as observed in 1997 with H5N1 or more recently with H7N9 and H10N8 viruses. Comparative analysis of the adaptive mutations in polymerases of different viruses indicates that their impact on the phylogenetically related H9N2 and H7N9 polymerases is higher than on the non related H7N7 and H1N1pdm09 polymerases. Analysis of polymerase reassortants composed of subunits of different viruses demonstrated that the efficient enhancement of polymerase activity by H9N2-PB2 does not depend on PA and PB1. These observations suggest that the PB2 subunit of the H9N2 polymerase has a high adaptive potential and may therefore be an important pandemic risk factor. PMID- 26560089 TI - Factors Governing the Bridging Water Protonation State in Polynuclear Mg(2+) Proteins. AB - An aqua ligand bridges metal cations in a wide variety of enzymes, many of which are drug targets for various diseases. However, the factors affecting its protonation state and thus biological roles remain elusive. By computing the free energy for replacing the bridging H2O by OH(-) in various model Mg(2+) sites, we have evaluated how the nature of an aqua bridge depends on the site's net charge (i.e., the number of charged ligands in the first and second shell and the number of metal cations), the site's solvent exposure, the ligand's charge-donating ability, the bridging oxygen's hydrogen-bonding interactions, intramolecular proton transfer from the bridging H2O to a nearby carboxylate, and the metal coordination number. The results reveal the key factors dictating the protonation state of bridging H2O and provide guidelines in predicting whether H2O or OH(-) bridges two Mg(2+) in polynuclear sites. This helps to elucidate the nucleophile in the enzyme-catalyzed reaction and the net charge of the metal complex (metal cation and first-shell ligands), which plays a critical role in binding. PMID- 26560091 TI - Second-Order Nonlinear Optical Properties of a Dithienylethene Indolinooxazolidine Hybrid: A Joint Experimental and Theoretical Investigation. AB - The nonlinear optical (NLO) properties of a double photochrome molecular switch are reported for the first time by considering the four trans forms of a dithienylethene-indolinooxazolidine hybrid. The four forms are characterized by means of hyper-Rayleigh scattering (HRS) experiments and quantum chemical calculations. Experimental measurements provide evidence that the pH- and light triggered transformations between the different forms of the hybrid are accompanied by large variations of the first hyperpolarizability, which makes this compound an effective multistate NLO switch. Quantum chemical calculations conducted at the time-dependent Hartree-Fock and time-dependent DFT levels agree with the experimental data and allow a complete rationalization of the NLO responses of the different forms. The HRS signal of the forms with an open indolinooxazolidine moiety are more than one order of magnitude larger than that measured for the other forms, whereas the open/closed status of the dithienylethene subunit barely influences the dynamic NLO properties. However, extrapolation of the NLO responses to the static limit leads to univocally distinguishable intrinsic responses for three of the various forms. This hybrid system thus acts as a highly efficient multistate NLO switch for eventual exploitation in optical memory systems with multiple storage and nondestructive readout capacity. PMID- 26560092 TI - Latin American Immigration to the United States. PMID- 26560093 TI - Lower limb function and 10-year survival in population aged 75 years and older. AB - BACKGROUND: Scientific societies recommend assessing lower limb function in usual clinical practice. The Short Physical Performance Battery (SPPB) is one of the most validated tools to assess this, but its capacity to predict long-term mortality in very old population attending primary care has not been studied. OBJECTIVE: To assess the ability of the SPPB to predict 10-year survival in individuals aged 75 and over. METHODS: Prospective cohort study with a 10-year follow-up. A representative sample of people aged 75 years or older without severe dependence (Barthel Index > 20) treated at a Spanish primary care centre (n = 315). Baseline evaluation included geriatric assessment with most well-known death predictors. The three SPPB subtasks (standing balance, walking speed and chair stand tests) were administered. Kaplan-Meier curves and Cox proportional hazard models were calculated for all-cause mortality. RESULTS: Mean age was 81.9 years (60.6% female). Ten-year survival of elders with SPPB score <7 and >=7 was 0.23 and 0.37 (P < 0.001), respectively. This difference remained statistically significant in the Cox model adjusted by age, gender, number of drugs prescribed, cognitive status, body mass index and visual sharpness (adjusted hazard ratio = 1.37; 95% confidence interval: 1.01-1.86). Also, walking speed and chair stand subtasks were both individual-independent predictors of 10-year survival. CONCLUSIONS: Our findings indicate that SPPB is an independent predictor of long term survival. The chair stand subtask could be a predictor as useful as the full performance battery, becoming a good alternative for primary care where the burden of performing all three subtasks could be excessive. PMID- 26560095 TI - Abstracts of the 26th Regional Congress of the International Society of Blood Transfusion in conjunction with the 6(th) Annual Conference of The Indonesian Society of Transfusion Medicine, Bali, Indonesia, November 14-16, 2015. PMID- 26560094 TI - A randomized controlled trial of the effect of an intensive 1-year care management program on measures of health status in independent, community-living old elderly: the Eldercare project. AB - BACKGROUND: Primary care practitioners are familiar with the frail elderly and commonly have to deal with their multi-morbidity and their functional decline, both physically and mentally. However, there are well elderly with high quality of life and very few co-morbidities who seldom seek medical care. OBJECTIVE: To determine if a nurse-based program of home-delivered care, linked directly with the primary care practitioner or primary care team, would improve quality of life, symptoms, satisfaction with care and utilization of community and medical services, in independent community living old elderly. DESIGN: Randomized controlled trial. SETTING: St. John's, Newfoundland, Canada. PARTICIPANTS: Two hundred and thirty-six independent, community-dwelling, cognitively functioning, people aged 80 years and older. INTERVENTION: A nurse-based program of care, carried out in the patients home, that involved a detailed assessment of needs, the development of a plan to meet the needs, and up to eight visits to the patients home during a 1-year period to facilitate the meeting of those needs. CONTROL GROUP: Usual care MAIN OUTCOME MEASUREMENTS: Quality of Life measured using the SF-36 and the CASP-19 scales; symptomology using the Comorbidity Symptom Scale; patient satisfaction using the PSQ-18; and assessment of health care services (community services, emergency room visits, hospitalizations, use of diagnostic services and family doctor visits) through patient recall, family physician chart review and assessment of hospitalization records. RESULTS: There were no statistical or meaningful differences between the intervention and control groups in any of the outcomes measured. CONCLUSION: The intensive, home delivered, program of care for the well old elderly did not have an impact on the outcomes measured. PMID- 26560097 TI - Safety of proton pump inhibitors and risk of gastric cancers: review of literature and pathophysiological mechanisms. AB - INTRODUCTION: Despite being an overall safe drug, several long-term adverse effects are associated with proton pump inhibitors (PPIs). The link between PPI use and gastric neuroendocrine tumors (NETs), gastric adenocarcinomas and Barrett's esophagus progression gastric cancers has been investigated due to PPI induced hypergastrinemia. AREAS COVERED: The pathophysiological mechanisms underlying PPI exposure and gastric NETs, gastric adenocarcinomas and Barrett's esophagus progression are discussed. The quality of randomized control studies, cohort studies and case reports investigating the link between gastric cancers and PPIs are examined. Recommendations for clinicians are provided. EXPERT OPINION: PPIs cause a hypergastrinemic state, increasing enterochromaffin-like cell dysplasia and risk of gastric NET development, increasing gastritis severity in the context of Helicobacter pylori infection, and progression of carcinogenesis in a certain predisposed subset of Barrett's esophagus patients. There are case reports of PPI-induced gastric NETs and adenocarcinomas as consequences of these effects. In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric NET development with chronic PPI use in these patients. Eradication status of H. pylori prior to commencing long-term PPI therapy should be established to reduce the risk of severe atrophic gastritis and development of gastric dysplasia. PMID- 26560098 TI - Ecological Effects of Biochar on the Structure and Function of Stream Benthic Communities. AB - The introduction of biochar, activated carbon, and other carbonaceous materials to aquatic ecosystems significantly reduces the toxicity and bioavailability of contaminants. However, previous studies have shown that these materials can have negative effects on aquatic organisms. We conducted field and mesocosm experiments to test the hypothesis that biochar altered the structure and function of stream benthic communities. After 30 d in the field, colonization by stoneflies (Plecoptera) was significantly lower in trays containing biochar compared to the results from the controls. In stream mesocosms, biochar increased macroinvertebrate drift and significantly reduced community metabolism. However, most measures of community composition showed little variation among biochar treatments, and significant responses were limited to a single stonefly species (Capnia confusa). When benthic communities were simultaneously exposed to biochar and Cu, effects were primarily associated with metal exposure. Because it is unlikely that biochar treatments would be employed in uncontaminated areas, these moderately negative effects should be considered within the context of the positive benefits associated with reduced contaminant bioavailability and toxicity. Additional research is necessary to improve our understanding of the mechanisms responsible for biochar effects on benthic communities and to identify the optimal application rates and size fractions that will maximize contaminant sorption but minimize potential negative effects. PMID- 26560099 TI - Does Terminating the Avoidance of Cow's Milk Lead to Growth in Height. AB - BACKGROUND: Cow's milk allergy is known to result in decreased body height; accordingly, the aim of this study was to investigate whether termination of milk avoidance leads to an increase in body height. METHODS: Between 2010 and 2011, 253 children with food allergies who were >=2 years of age visited our outpatient department; 195 had height data available from approximately 1 year after their initial food allergy diagnosis and were included in the study. The height standard deviation scores (HtSDs) were calculated using data from the 2000 Japanese National Physical Growth Survey Report for Infants and Children, and changes in height were then retrospectively evaluated using clinical records. RESULTS: The mean age of the 195 patients was 5.8 +/- 3.0 years. The mean HtSDs increased significantly from -0.19 +/- 0.99 at diagnosis to -0.12 +/- 1.02 (p = 0.025) 1 year later for all children. The HtSDs of 110 cases had increased, but the HtSDs of 85 cases had decreased 1 year after the initial diagnosis. The only significant factor related to increased HtSD was tolerated milk allergy 1 year after the initial diagnosis (p = 0.004). CONCLUSIONS: Terminating the avoidance of cow's milk might lead to growth in height, although a prospective study with a larger sample size is needed to confirm these results. PMID- 26560096 TI - Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation. AB - SIGNIFICANCE: Traumatic injury elicits a complex, dynamic, multidimensional inflammatory response that is intertwined with complications such as multiple organ dysfunction and nosocomial infection. The complex interplay between inflammation and physiology in critical illness remains a challenge for translational research, including the extrapolation to human disease from animal models. RECENT ADVANCES: Over the past decade, we and others have attempted to decipher the biocomplexity of inflammation in these settings of acute illness, using computational models to improve clinical translation. In silico modeling has been suggested as a computationally based framework for integrating data derived from basic biology experiments as well as preclinical and clinical studies. CRITICAL ISSUES: Extensive studies in cells, mice, and human blunt trauma patients have led us to suggest (i) that while an adequate level of inflammation is required for healing post-trauma, inflammation can be harmful when it becomes self-sustaining via a damage-associated molecular pattern/Toll like receptor-driven feed-forward circuit; (ii) that chemokines play a central regulatory role in driving either self-resolving or self-maintaining inflammation that drives the early activation of both classical innate and more recently recognized lymphoid pathways; and (iii) the presence of multiple thresholds and feedback loops, which could significantly affect the propagation of inflammation across multiple body compartments. FUTURE DIRECTIONS: These insights from data driven models into the primary drivers and interconnected networks of inflammation have been used to generate mechanistic computational models. Together, these models may be used to gain basic insights as well as serving to help define novel biomarkers and therapeutic targets. PMID- 26560100 TI - Integrative phenotyping framework (iPF): integrative clustering of multiple omics data identifies novel lung disease subphenotypes. AB - BACKGROUND: The increased multi-omics information on carefully phenotyped patients in studies of complex diseases requires novel methods for data integration. Unlike continuous intensity measurements from most omics data sets, phenome data contain clinical variables that are binary, ordinal and categorical. RESULTS: In this paper we introduce an integrative phenotyping framework (iPF) for disease subtype discovery. A feature topology plot was developed for effective dimension reduction and visualization of multi-omics data. The approach is free of model assumption and robust to data noises or missingness. We developed a workflow to integrate homogeneous patient clustering from different omics data in an agglomerative manner and then visualized heterogeneous clustering of pairwise omics sources. We applied the framework to two batches of lung samples obtained from patients diagnosed with chronic obstructive lung disease (COPD) or interstitial lung disease (ILD) with well-characterized clinical (phenomic) data, mRNA and microRNA expression profiles. Application of iPF to the first training batch identified clusters of patients consisting of homogenous disease phenotypes as well as clusters with intermediate disease characteristics. Analysis of the second batch revealed a similar data structure, confirming the presence of intermediate clusters. Genes in the intermediate clusters were enriched with inflammatory and immune functional annotations, suggesting that they represent mechanistically distinct disease subphenotypes that may response to immunomodulatory therapies. The iPF software package and all source codes are publicly available. CONCLUSIONS: Identification of subclusters with distinct clinical and biomolecular characteristics suggests that integration of phenomic and other omics information could lead to identification of novel mechanism-based disease sub-phenotypes. PMID- 26560101 TI - A Reappraisal of the Purported Gastric Pellet with Pterosaurian Bones from the Upper Triassic of Italy. AB - A small accumulation of bones from the Norian (Upper Triassic) of the Seazza Brook Valley (Carnic Prealps, Northern Italy) was originally (1989) identified as a gastric pellet made of pterosaur skeletal elements. The specimen has been reported in literature as one of the very few cases of gastric ejecta containing pterosaur bones since then. However, the detailed analysis of the bones preserved in the pellet, their study by X-ray microCT, and the comparison with those of basal pterosaurs do not support a referral to the Pterosauria. Comparison with the osteology of a large sample of Middle-Late Triassic reptiles shows some affinity with the protorosaurians, mainly with Langobardisaurus pandolfii that was found in the same formation as the pellet. However, differences with this species suggest that the bones belong to a similar but distinct taxon. The interpretation as a gastric pellet is confirmed. PMID- 26560103 TI - Effect of Different Groundwater Levels on Seismic Dynamic Response and Failure Mode of Sandy Slope. AB - Heavy seismic damage tends to occur in slopes when groundwater is present. The main objectives of this paper are to determine the dynamic response and failure mode of sandy slope subjected simultaneously to seismic forces and variable groundwater conditions. This paper applies the finite element method, which is a fast and efficient design tool in modern engineering analysis, to evaluate dynamic response of the slope subjected simultaneously to seismic forces and variable groundwater conditions. Shaking table test is conducted to analyze the failure mode and verify the accuracy of the finite element method results. The research results show that dynamic response values of the slope have different variation rules under near and far field earthquakes. And the damage location and pattern of the slope are different in varying groundwater conditions. The destruction starts at the top of the slope when the slope is in no groundwater, which shows that the slope appears obvious whipping effect under the earthquake. The destruction starts at the toe of the slope when the slope is in the high groundwater levels. Meanwhile, the top of the slope shows obvious seismic subsidence phenomenon after earthquake. Furthermore, the existence of the groundwater has a certain effect of damping. PMID- 26560102 TI - Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model. AB - We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo) of Brugia malayi (B. malayi) in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo) and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo) in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+) and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%+/-2.32) against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%+/-2.23) and pcD Myo (41.6%+/-2.45). In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC) to B. malayi infective larvae (L3). pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-gamma) and anti-inflammatory (IL-4, IL-10) cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of providing high degree of protection against filarial larval invasion. PMID- 26560104 TI - Comment on "Effects of Reduction Mammaplasty Operations on the Spinal Column: Clinical and Radiological Response". PMID- 26560105 TI - Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study. AB - European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested. PMID- 26560106 TI - Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes. AB - Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of future midshipman and cross species comparative studies of the auditory periphery. PMID- 26560107 TI - Fluid retention, muscle damage, and altered body composition at the Ultraman triathlon. AB - PURPOSE: The primary purpose of this investigation was to determine the effects of participation in a 3-day multistage ultraendurance triathlon (stage 1 = 10 km swim, 144.8 km bike; stage 2 = 275.4 km bike; stage 3 = 84.4 km run) on body mass and composition, hydration status, hormones, muscle damage, and blood glucose. METHODS: Eighteen triathletes (mean +/- SD; age 41 +/- 7.5 years; height 175 +/- 9 cm; weight 73.5 +/- 9.8 kg; male n = 14, female n = 4) were assessed before and after each stage of the race. Body mass and composition were measured via bioelectrical impedance, hydration status via urine specific gravity, hormones and muscle damage via venous blood draw, and blood glucose via fingerstick. RESULTS: Following the race, significant changes included reductions in body mass (qualified effect size: trivial), fat mass (moderate), and percent body fat (small); increases in percent total body water (moderate) and urine specific gravity (large); and unchanged absolute total body water and fat-free mass. There were also extremely large increases in creatine kinase, C-reactive protein, aldosterone and cortisol combined with reductions in testosterone (small) and the testosterone:cortisol ratio (moderate). There were associations between post-race aldosterone and total body water (r = -0.504) and changes in cortisol and fat free mass (r = -0.536). Finally, blood glucose increased in a stepwise manner prior to each stage. CONCLUSIONS: Participation in Ultraman Florida leads to fluid retention and dramatic alterations in body composition, muscle health, hormones, and metabolism. PMID- 26560108 TI - History-dependent changes in the recovery process of the middle latency cutaneous reflex gain after ankle sprain injury. AB - PURPOSE: We previously reported that suppressive middle latency cutaneous reflexes (MLRs) in the peroneus longus (PL) are exaggerated in subjects with chronic ankle instability, and the changes are related to functional instability. However, the time-varying history of these neurophysiological changes after an ankle sprain is yet to be elucidated. Therefore, in the present study, we investigated the time course of the changes in the PL MLR after an ankle sprain in relation to the number of sprain recurrences. METHODS: Twenty-three subjects with ankle sprain were classified into 3 groups according to their history of ankle sprain: first ankle sprain, 2-3 ankle sprains, and >=4 ankle sprains. Twenty-three age-matched control subjects also participated. The PL MLRs were elicited by stimulating the sural nerve while the subjects performed different levels of isometric ankle eversion. Gain of MLR was estimated using linear regression analysis (slope value) of the amplitude modulation of MLRs obtained from graded isometric contractions. RESULT: The gain of MLRs first increased 4 weeks after the injury. In subjects with their first ankle sprain, the MLRs returned to almost baseline levels after 3 months. In contrast, the increase in MLR gain persisted even after 3 months in subjects with recurrent ankle sprains. In addition, the MLR gains were closely related to functional recovery of the ankle joint. CONCLUSIONS: Our findings suggest that the recovery process of MLR gains were strongly affected by the history of ankle sprains as well as the functional recovery of the ankle joint. PMID- 26560110 TI - Are wound ring protectors effective in reducing surgical site infection post appendectomy? A systematic review and meta-analysis. AB - INTRODUCTION: Surgical site infection (SSI) is one of the main causes of postoperative morbidity and mortality. Appendectomy for acute appendicitis is one of the most commonly performed surgical interventions worldwide. The use of ring retractors to protect the wound edge from contaminated intra-abdominal contents may be an effective method to reduce SSI. AIM: The aim of this systematic review and meta-analysis is to determine whether the use of wound ring retractors reduces SSI rates after open appendectomy. METHODS: A systematic review of randomized controlled trials (RCTs) and meta-analysis of ring retractors was undertaken using the PRISMA guidelines. PubMed, Cochrane RCTs Central Register, CINAHL, and ISRCTN registry were searched for eligible studies. Only studies in which open appendectomy was undertaken were included. The Cochrane Collaboration's RevMan 5.3 was used for analysis. A subgroup analysis by degree of appendiceal inflammation was performed. RESULTS: Four RCTs inclusive of 939 patients met eligibility requirements. One trial used single ring while three used double ring protectors. Differences in the definition of SSI, skin preparation, and type and duration of prophylactic antibiotic were found between the 4 studies. The use of ring retractors show some evidence of SSI reduction risk ratio 0.44 [95 % CI (0.21, 0.90)]. On sub-analysis, ring retractor was more effective in more severe degrees of appendiceal inflammation i.e., the contaminated group. CONCLUSION: Our review suggests some benefit in using ring retractors to reduce SSI post appendectomy; however the small number and variable quality of the studies suggest the need for more RCTs to confirm these results. PMID- 26560109 TI - Is there a role for antifibrinolytics in pelvic and acetabular fracture surgery? AB - BACKGROUND: Pelvic and acetabular fractures are rare, complex injuries associated with significant morbidity. Fixation of these injuries requires major orthopaedic surgery which in itself is associated with substantial blood loss owing to the extensile operative approach and prolonged operating time required to address the complex fracture anatomy. In order to reduce morbidity, a multifactor approach to blood conservation must be adopted. CURRENT ROLE OF ANTIFIBRINOLYTICS IN ORTHOPAEDIC SURGERY: The use of antifibrinolytics to reduce operative blood loss is well documented in many surgical specialties, including orthopaedic surgery. Elective spinal surgery and joint arthroplasty have benefited from the introduction of antifibrinolytics; however, their role in trauma and fracture surgery is not fully defined. Pelvic and acetabular fracture surgery would benefit from further investigation on the benefit and safety of these agents. CONCLUSION: Routine use cannot be recommended at this time but agents may be considered on a case-specific basis. PMID- 26560111 TI - Effectiveness of retrograde intrarenal stone surgery in obese patients. AB - BACKGROUND: A number of comorbid health problems can be found in obese patients. These problems increase the surgical risk in obese patients. AIMS: To determine the effectiveness of retrograde intrarenal surgery for renal stone treatment in obese patients. METHODS: We retrospectively reviewed the data of 106 patients who had retrograde intrarenal surgery with the diagnosis of renal stone in our clinic. The patients were divided into three groups regarding their body mass indexes: >=30 kg/m2 being obese (group 1), 25-29.9 kg/m2 being overweight (group 2), and <25 kg/m2 being normal weight (group 3). The patients were compared for age, gender, and stone characteristics. In addition, the duration of surgery, stone-free rate (SFR), complication rate, and the duration of the hospital stay were compared among the groups. RESULTS: Twenty eight patients were obese (group 1), 49 patients were overweight (group 2), and 29 patients were normal weight (group 3). The mean ages of groups 1, 2 and 3 were 51.5 (29-84), 47 (30-76) and 35 (19-84) years, respectively (p = 0.001). SFR was 85.7 % in group 1, 89.8 % in group 2, and 75.9 % in group 3 (p = 0.24). The duration of surgery was similar in groups 1, 2, and 3, being 45.5 (25-95), 50 (30-120), and 45.5 (10-100) min, respectively (p = 0.23). None of the patients had major complications. CONCLUSIONS: Our results indicate that retrograde intrarenal surgery is a safe and efficient surgical method for renal stone treatment in obese and overweight patients. PMID- 26560112 TI - Floral nectar production and carbohydrate composition and the structure of receptacular nectaries in the invasive plant Bunias orientalis L. (Brassicaceae). AB - The data relating to the nectaries and nectar secretion in invasive Brassicacean taxa are scarce. In the present paper, the nectar production and nectar carbohydrate composition as well as the morphology, anatomy and ultrastructure of the floral nectaries in Bunias orientalis were investigated. Nectary glands were examined using light, fluorescence, scanning electron and transmission electron microscopy. The quantities of nectar produced by flowers and total sugar mass in nectar were relatively low. Total nectar carbohydrate production per 10 flowers averaged 0.3 mg. Nectar contained exclusively glucose (G) and fructose (F) with overall G/F ratio greater than 1. The flowers of B. orientalis have four nectaries placed at the base of the ovary. The nectarium is intermediate between two nectary types: the lateral and median nectary type (lateral and median glands stay separated) and the annular nectary type (both nectaries are united into one). Both pairs of glands represent photosynthetic type and consist of epidermis and glandular tissue. However, they differ in their shape, size, secretory activity, dimensions of epidermal and parenchyma cells, thickness of secretory parenchyma, phloem supply, presence of modified stomata and cuticle ornamentation. The cells of nectaries contain dense cytoplasm, plastids with starch grains and numerous mitochondria. Companion cells of phloem lack cell wall ingrowths. The ultrastructure of secretory cells indicates an eccrine mechanism of secretion. Nectar is exuded throughout modified stomata. PMID- 26560113 TI - Drought tolerance and proteomics studies of transgenic wheat containing the maize C4 phosphoenolpyruvate carboxylase (PEPC) gene. AB - Enhancing drought tolerance of crops has been a great challenge in crop improvement. Here, we report the maize phosphoenolpyruvate carboxylase (PEPC) gene was able to confer drought tolerance and increase grain yield in transgenic wheat (Triticum aestivum L.) plants. The improved of drought tolerance was associated with higher levels of proline, soluble sugar, soluble protein, and higher water use efficiency. The transgenic wheat plants had also a more extensive root system as well as increased photosynthetic capacity during stress treatments. The increased grain yield of the transgenic wheat was contributed by improved biomass, larger spike and grain numbers, and heavier 1000-grain weight under drought-stress conditions. Under non-stressed conditions, there were no significant increases in these of the measured traits except for photosynthetic rate when compared with parental wheat. Proteomic research showed that the expression levels of some proteins, including chlorophyll A-B binding protein and pyruvate, phosphate dikinase, which are related to photosynthesis, PAP fibrillin, which is involved in cytoskeleton synthesis, S-adenosylmethionine synthetase, which catalyzes methionine synthesis, were induced in the transgenic wheat under drought stress. Additionally, the expression of glutamine synthetase, which is involved in ammonia assimilation, was induced by drought stress in the wheat. Our study shows that PEPC can improve both stress tolerance and grain yield in wheat, demonstrating the efficacy of PEPC in crop improvement. PMID- 26560114 TI - Current trends in Bt crops and their fate on associated microbial community dynamics: a review. AB - Cry protein expressing insect-resistant trait is mostly deployed to control major devastating pests and minimize reliance on the conventional pesticides. However, the ethical and environmental issues are the major constraints in their acceptance, and consequently, the cultivation of genetically modified (GM) crops has invited intense debate. Since root exudates of Bacillus thuringiensis (Bt) crops harbor the insecticidal protein, there is a growing concern about the release and accumulation of soil-adsorbed Cry proteins and their impact on non target microorganisms and soil microbial processes. This review pertains to reports from the laboratory studies and field trials to assess the Bt toxin proteins in soil microbes and the processes determining the soil quality in conjunction with the existing hypothesis and molecular approaches to elucidate the risk posed by the GM crops. Ecological perturbations hinder the risk aspect of soil microbiota in response to GM crops. Therefore, extensive research based on in vivo and interpretation of results using high-throughput techniques such as NGS on risk assessment are imperative to evaluate the impact of Bt crops to resolve the controversy related to their commercialization. But more studies are needed on the risk associated with stacked traits. Such studies would strengthen our knowledge about the plant-microbe interactions. PMID- 26560115 TI - Knowledge that people with intellectual disabilities have of their inhaled asthma medications: messages for pharmacists. AB - BACKGROUND: Fifteen percent of Australians with intellectual disability (ID) are reported to have asthma. People with ID are at risk of poor health knowledge due to deficits in intellectual and adaptive functioning, but their medication knowledge has largely been ignored in research to date. OBJECTIVE: To explore the level of understanding of asthma medication use of people with ID who self administer their inhaled medications, in order to inform future educational support. Setting The research was conducted in NSW, Australia, at the participants' homes, the point of health care access, or the offices of relevant support organisations. METHOD: In this qualitative study face-to-face interviews were conducted with people with ID using a semi-structured interview guide. The interviews were recorded, transcribed and thematically analysed. Main outcome Identification of barriers to asthma medication self-management by people with ID. RESULTS: Seventeen people with ID who self-administer their asthma medications were interviewed. Factors influencing their asthma medication knowledge and use included understanding of their illness and the need for medication; aspects of self-management and autonomy versus dependence. This sample of people with ID had a good understanding of the importance of using their inhaled asthma medications, as well as asthma triggers, and the difference between use of preventer and reliever medications. Both enablers and barriers to asthma medication self-management were identified in the domains of managing attacks, adherence, knowledge of side effects and sources of information on correct use of inhalers. The level of autonomy for medication use varied, with motivation to self-manage asthma influenced by the level of support that was practically available to individual participants. CONCLUSION: This research investigated aspects of asthma medication self-management of people with ID. Based on the barriers identified, pharmacists should promote use of spacers and written asthma action plans as well as counsel people with ID about how to recognise and minimise side effects of asthma medications. Specific strategies for pharmacists when educating people with ID and their caregivers include active listening to determine understanding of concepts, exercising care with language, and working with the person's known routines to maximise adherence with preventer medications. PMID- 26560116 TI - RING-, HECT-, and RBR-type E3 Ubiquitin Ligases: Involvement in Human Cancer. AB - In the ubiquitylation system, E3 ubiquitin ligases play a key role in determining substrate specificity and catalyzing the transfer of ubiquitin from E2 enzymes to the substrate. Growing evidence has shown that E3 ubiquitin ligases are involved in cancer development and progression. The RING-type and HECT-type E3 ligases are the classically categorized groups of E3 ubiquitin ligases, and more of these enzymes are being shown to be potential targets for cancer therapy. The recently classified RBR E3 ligases catalyze the transfer of ubiquitin by a RING/HECT hybrid-like mechanism. Notably, these ligases are also emphasized as important potential candidates for targets of cancer treatment drugs. The present review provides an overview of the RING-, HECT- and RBR-type E3 ligases, and discusses their roles in cancer and cancer therapy. PMID- 26560117 TI - Tribbles-Related Protein Family Members as Regulators or Substrates of the Ubiquitin-Proteasome System in Cancer Development. AB - Tribbles-related protein (TRB) family members are the mammalian orthologs of Drosophila tribbles. Tribbles was originally identified as a cell cycle regulator during Drosophila development. Tribbles genes are evolutionary conserved, and three TRB genes (TRB1, TRB2 and TRB3) have been identified in mammals. TRBs are considered pseudokinases because they lack an ATP binding site or one of the conserved catalytic motifs essential for kinase activity. Instead, TRBs play important roles in various cellular processes as scaffolds or adaptors to promote the degradation of target proteins and to regulate several key signaling pathways. Recent research has focused on the role of TRBs in tumorigenesis and neoplastic progression. In this review, we focus on the physiological roles of TRB family members in tumorigenesis through the regulation of the ubiquitin proteasome system and discuss TRBs as biomarkers or potential therapeutic targets in cancer. PMID- 26560118 TI - Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy. AB - Selective degradation of pathogenic proteins by small molecules in cells is a novel approach for development of therapeutic agents against various diseases, including cancer. We and others have developed a protein knockdown technology with a series of hybrid small compounds, called SNIPERs (Specific and Nongenetic IAP-dependent Protein ERasers); and peptidic chimeric molecules, called PROTACs (proteolysis-targeting chimeric molecules), which induce selective degradation of target proteins via the ubiquitin-proteasome pathway. These compounds include two different ligands connected by a linker; one is a ligand for a ubiquitin ligase and the other is a ligand for the target protein, which are expected to crosslink these proteins in cells. Theoretically, any cytosolic protein can be targeted for degradation by this technology. To date, several SNIPERs and PROTACs against various oncogenic proteins have been developed, which specifically induce polyubiquitylation and proteasomal degradation of the oncogenic proteins, resulting in cell death, growth arrest, or impaired migration of cancer cells. Thus, this protein knockdown technology has a great potential for cancer therapy. PMID- 26560119 TI - E3 Ubiquitin Ligases as Molecular Targets in Human Oral Cancers. AB - The ubiquitin-proteasome pathway is involved in various biological processes. Several oncogenic E3 ligases target tumor suppressor proteins for ubiquitin mediated degradation. Alternatively, some other E3 ligases play as a tumor suppressor specifically targeting oncogene products. Deregulation of these E3 ligases induces unbalance between oncogenic signal and tumor suppressor pathway and leads to cellular transformation, tumor growth and metastasis in various human malignancies including oral, and head and neck cancers. Facilitated degradation of the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) has been observed in oral, and head and neck cancers, and is correlated with their poor prognosis. SCF(Skp2), KPC complex, Pirh2 and CRL4(DDB2-Artemis) have been reported as E3 ligases targeting p27(Kip1) for degradation. In oral cancers, it is reported that overexpression of Skp2 and Pirh2 is associated with poor prognosis. Thus, chemical inhibitors against these E3 ligases are applicable for oral cancer therapy. Some potential compounds that inhibit E3 ligase activity of SCF(Skp2) have been reported. Moreover, the HECT-type E3 ligase WWP family and Smurf1 are also involved in the development and growth of human oral cancers. Therefore, small molecule inhibitors against HECT-type E3 ligases are discussed as anti-oral cancer drugs. PMID- 26560120 TI - The SCF-type E3 Ubiquitin Ligases as Cancer Targets. AB - The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis, prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug resistance, and DNA-damage responses. PMID- 26560121 TI - Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer. AB - Epithelial-mesenchymal transition (EMT) plays an important role in the development of tumor metastases by facilitating cell migration and invasion. One of the hallmarks of EMT is the diminished expression of E-cadherin and gain of mesenchymal traits, which are regulated by core EMT-inducing transcriptional factors (EMT-TFs), such as Snail/Slug, ZEB1/ZEB2, and Twist1. EMT-TFs are known to be extremely labile proteins, and their protein levels are tightly controlled by the ubiquitin-proteasome system (UPS). Several E3 ubiquitin ligases have been shown to play crucial roles in the regulation of EMT, and genetic aberrations and alterations in these ligases have been detected in human cancer. In this review, we focused on EMT-TFs, describing the UPS controlling their activities and functions in cancer. A deeper understanding of the role of UPS in the regulation of EMT will provide valuable information for the development of effective anti metastatic drugs to modulate the malignant processes mediated by EMT. PMID- 26560122 TI - Biostabilization and Transport of Cohesive Sediment Deposits in the Three Gorges Reservoir. AB - Cohesive sediment deposits in the Three Gorges Reservoir, China, were used to investigate physical and geochemical properties, biofilm mass, and erosion and deposition characteristics. Biofilm cultivation was performed in a recirculating flume for three different periods (5, 10 and 15 days) under ambient temperature and with sufficient nutrients supply. Three groups of size-fractionated sediment were sequentially used, including 0-0.02 mm, 0.02-0.05 mm and 0.05-0.10 mm. Desired conditions for erosion and deposition were designed by managing high bed shear stress at the narrow part of upstream flume and low shear stress at the wide part of downstream flume. Biostabilization and transport characteristics of the biofilm coated sediment (bio-sediment) were strongly influenced by the cultivation period, and the results were compared with clean sediment. The bio sediment was more resistant to erosion, and the mean shear stress was increased by factors of 2.65, 2.73 and 5.01 for sediment with 5, 10 and 15 days of biofilm growth compared with clean sediment, resulting in less sediment being eroded from the bed. Simultaneously, the settling velocity was smaller for bio-sediment due to higher organic content and porosity (i.e., lower density). Additionally, there was a smaller probability of deposition for sediment with a longer cultivation period after erosion, resulting in more retention time in aquatic systems. These results will benefit water management in natural rivers. PMID- 26560123 TI - "1-2-3 Pap" Intervention Improves HPV Vaccine Series Completion among Appalachian Women. AB - Completion of the Human Papillomavirus (HPV) vaccine series is a national priority. This study not only identified correlates of intent to complete the vaccine series and actual series completion, but also tested the efficacy of a DVD intervention to promote series completion. Women's beliefs that all three doses reduced cancer risk predicted intent and completion. Intention predicted completion, as did the belief that having a friend accompany the woman would promote completion. Beyond these effects, women assigned to the intervention were 2.44 times more likely than women in the control group to complete the series. Thus, in controlled analyses, a theory-grounded DVD intervention successfully promoted HPV series completion in a community setting. This method of intervention has high translational potential. PMID- 26560124 TI - CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer. AB - BACKGROUND: Cancerous inhibitor of PP2A (CIP2A) is a recently characterized oncoprotein, which promotes cancer cell proliferation. But the role of CIP2A in lung cancer progression is still not well understood. METHODS: The expression level of CIP2A in lung cancer tissues was examined by immunohistochemistry. CIP2A associated cell proliferation was performed by knock down or overexpression of CIP2A in lung cancer cells. Phospho-array was used to screen kinase candidates related to expression change of CIP2A. Western-blot and luciferase reporter assay were used to validate phospho-array results. RESULTS: Overexpression of CIP2A in lung cancer not only triggers immune response in lung cancer patients but also promotes lung cancer cell proliferation. By phospho-array, several kinase candidates were identified, one of which is c-Jun activated kinases (JNK). The knock down of CIP2A decreased JNK phosphorylation, and the phosphorylation of downstream transcriptional factors, ATF2 and c-Jun, whose transcriptional activity were decreased as well. Furthermore, the expression level of CIP2A also affected the phosphorylation of the upstream kinase of JNK, MKK4/MKK7. At last, treatment with JNK inhibitor partially abolished CIP2A-induced cell proliferation. CONCLUSION: CIP2A is a tumor-associated autoantigen in lung cancer, which promote lung cancer proliferation partially through MKK4/7-JNK signaling pathway. PMID- 26560125 TI - Association between dental amalgam fillings and Alzheimer's disease: a population based cross-sectional study in Taiwan. AB - INTRODUCTION: The potential effects of amalgam fillings on the development of Alzheimer's disease (AD) are not well understood. The aim of the study was to evaluate the association between dental amalgam fillings and Alzheimer's disease in Taiwanese population aged 65 and older. METHODS: Data were retrieved from the Longitudinal Health Insurance Database (LHID 2005 and 2010). The study enrolled 1,943,702 beneficiaries from the LHID database. After excluding death cases and individuals aged 65 and under, 207,587 enrollees were finally involved in the study. Dental amalgam fillings are coded as 89001C, 89002C, 89003C, 89101C, 89102C, or 89103C in the national health insurance research database (NHIRD). Alzheimer's disease was diagnosed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 331.0. RESULTS: Individuals exposed to amalgam fillings had higher risk of Alzheimer's disease (odds ratio, OR = 1.105, 95 % confidence interval, CI = 1.025-1.190) than their non-exposed counterparts. Further analysis showed that the odds ratio of Ahlzheimer's disease was 1.07 (95 % CI = 0.962-1.196) in men and 1.132 (95 % CI = 1.022-1.254) in women. CONCLUSIONS: Women who were exposed to amalgam fillings were 1.132 times more likely to have Alzheimer's disease than were their non exposed counterparts. PMID- 26560126 TI - Hunt summons royal colleges for talks on preparing for industrial action. PMID- 26560128 TI - Erratum. PMID- 26560129 TI - Nonmarital Relationships and Changing Perceptions of Marriage Among African American Young Adults. AB - Cohabitation has become increasingly widespread over the past decade. Such trends have given rise to debates about the relation between cohabitation and marriage, in terms of what cohabitation means for individual relationship trajectories and for the institution of marriage more generally. Using recent data from a sample of almost 800 African Americans and fixed effects modeling procedures, in the present study the authors shed some light on these debates by exploring the extent to which cohabitation, relative to both singlehood and dating, was associated with within-individual changes in African Americans' marital beliefs during the transition to adulthood. The findings suggest that cohabitation is associated with changes in marital beliefs, generally in ways that repositioned partners toward marriage, not away from it. This was especially the case for women. These findings suggest that, for young African American women, cohabitation holds a distinct place relative to dating and, in principle if not practice, relative to marriage. PMID- 26560127 TI - Healthcare Databases in Thailand and Japan: Potential Sources for Health Technology Assessment Research. AB - BACKGROUND: Health technology assessment (HTA) has been continuously used for value-based healthcare decisions over the last decade. Healthcare databases represent an important source of information for HTA, which has seen a surge in use in Western countries. Although HTA agencies have been established in Asia Pacific region, application and understanding of healthcare databases for HTA is rather limited. Thus, we reviewed existing databases to assess their potential for HTA in Thailand where HTA has been used officially and Japan where HTA is going to be officially introduced. METHOD: Existing healthcare databases in Thailand and Japan were compiled and reviewed. Databases' characteristics e.g. name of database, host, scope/objective, time/sample size, design, data collection method, population/sample, and variables were described. Databases were assessed for its potential HTA use in terms of safety/efficacy/effectiveness, social/ethical, organization/professional, economic, and epidemiological domains. Request route for each database was also provided. RESULTS: Forty databases- 20 from Thailand and 20 from Japan-were included. These comprised of national censuses, surveys, registries, administrative data, and claimed databases. All databases were potentially used for epidemiological studies. In addition, data on mortality, morbidity, disability, adverse events, quality of life, service/technology utilization, length of stay, and economics were also found in some databases. However, access to patient-level data was limited since information about the databases was not available on public sources. CONCLUSION: Our findings have shown that existing databases provided valuable information for HTA research with limitation on accessibility. Mutual dialogue on healthcare database development and usage for HTA among Asia-Pacific region is needed. PMID- 26560130 TI - Morphological Heterogeneity and Attachment of Phaeobacter inhibens. AB - The Roseobacter clade is a key group of bacteria in the ocean exhibiting diverse metabolic repertoires and a wide range of symbiotic life-styles. Many Roseobacters possess remarkable capabilities of attachment to both biotic and abiotic surfaces. When attached to each other, these bacteria form multi-cellular structures called rosettes. Phaeobacter inhibens, a well-studied Roseobacter, exhibits various cell sizes and morphologies that are either associated with rosettes or occur as single cells. Here we describe the distribution of P. inhibens morphologies and rosettes within a population. We detect an N acetylglucosamine-containing polysaccharide on the poles of some cells and at the center of all rosettes. We demonstrate that rosettes are formed by the attachment of individual cells at the polysaccharide-containing pole rather than by cell division. Finally, we show that P. inhibens attachment to abiotic surfaces is hindered by the presence of DNA from itself, but not from other bacteria. Taken together, our findings demonstrate that cell adhesiveness is likely to play a significant role in the life cycle of P. inhibens as well as other Roseobacters. PMID- 26560131 TI - Capacity of Health Facilities to Manage Hypertension in Mukono and Buikwe Districts in Uganda: Challenges and Recommendations. AB - BACKGROUND: The burden of chronic diseases is increasing in both low- and middle income countries. However, healthcare systems in low-income countries are inadequately equipped to deal with the growing disease burden, which requires chronic care for patients. The aim of this study was to assess the capacity of health facilities to manage hypertension in two districts in Uganda. METHODS: In a cross-sectional study conducted between June and October 2012, we surveyed 126 health facilities (6 hospitals, 4 Health Center IV (HCIV), 23 Health Center III (HCIII), 41 Health Center II (HCII) and 52 private clinics/dispensaries) in Mukono and Buikwe districts in Uganda. We assessed records, conducted structured interviews with heads of facilities, and administered questionnaires to 271 health workers. The study assessed service provision for hypertension, availability of supplies such as medicines, guidelines and equipment, in-service training for hypertension, knowledge of hypertension management, challenges and recommendations. RESULTS: Of the 126 health facilities, 92.9% reported managing (diagnosing/treating) patients with hypertension, and most (80.2%) were run by non-medical doctors or non-physician health workers (NPHW). Less than half (46%) of the facilities had guidelines for managing hypertension. A 10th of the facilities lacked functioning blood pressure devices and 28% did not have stethoscopes. No facilities ever calibrated their BP devices except one. About a half of the facilities had anti-hypertensive medicines in stock; mainly thiazide diuretics (46%), beta blockers (56%) and calcium channel blockers (48.4%). Alpha blockers, mixed alpha & beta blockers and angiotensin II receptor antagonists were only stocked by private clinics/dispensaries. Most HCIIs lacked anti hypertensive medicines, including the first line thiazide diuretics. Significant knowledge gaps in classification of patients as hypertensive were noted among respondents. All health workers (except 5, 1.9%) indicated that they needed additional training in hypertension management. Several provider and patient related challenges were also observed in this study. CONCLUSIONS: Health facilities in this setting are inadequately equipped to provide services for management of hypertension. Diagnostic equipment, anti-hypertensive drugs and personnel present great challenges. To address the increasing burden of hypertension and other chronic diseases, measures are needed to substantially strengthen the healthcare facilities, including training of personnel in management of hypertension and other chronic diseases, and improving diagnostic and treatment supplies. PMID- 26560132 TI - Development of a decision analytic model to support decision making and risk communication about thrombolytic treatment. AB - BACKGROUND: Individualised prediction of outcomes can support clinical and shared decision making. This paper describes the building of such a model to predict outcomes with and without intravenous thrombolysis treatment following ischaemic stroke. METHODS: A decision analytic model (DAM) was constructed to establish the likely balance of benefits and risks of treating acute ischaemic stroke with thrombolysis. Probability of independence, (modified Rankin score mRS <= 2), dependence (mRS 3 to 5) and death at three months post-stroke was based on a calibrated version of the Stroke-Thrombolytic Predictive Instrument using data from routinely treated stroke patients in the Safe Implementation of Treatments in Stroke (SITS-UK) registry. Predictions in untreated patients were validated using data from the Virtual International Stroke Trials Archive (VISTA). The probability of symptomatic intracerebral haemorrhage in treated patients was incorporated using a scoring model from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) data. RESULTS: The model predicts probabilities of haemorrhage, death, independence and dependence at 3-months, with and without thrombolysis, as a function of 13 patient characteristics. Calibration (and inclusion of additional predictors) of the Stroke-Thrombolytic Predictive Instrument (S-TPI) addressed issues of under and over prediction. Validation with VISTA data confirmed that assumptions about treatment effect were just. The C-statistics for independence and death in treated patients in the DAM were 0.793 and 0.771 respectively, and 0.776 for independence in untreated patients from VISTA. CONCLUSIONS: We have produced a DAM that provides an estimation of the likely benefits and risks of thrombolysis for individual patients, which has subsequently been embedded in a computerised decision aid to support better decision-making and informed consent. PMID- 26560133 TI - The quantitative evaluation of the impact of viable medial meniscus graft type on the biochemical and biomechanical properties of the rabbit tibial cartilage. AB - BACKGROUND: Knowledge of the impact of viable medial meniscus allograft and autograft transplantation on biochemical and mechanical properties of cartilage is needed to understand the development of joint osteoarthritis. The purpose of this study was to evaluate this relationship 6 months after viable medial meniscal autograft and allograft transplantation. METHODS: Twenty rabbits were chosen for the study. The medial menisci were excised from 14 animals and stored under tissue culture conditions for 2 weeks. Seven menisci were implanted as autografts (group A) and seven as allografts (group B). The control group consisted of six animals which underwent arthrotomy. The tibial cartilage was used for mechanical and biochemical evaluation. RESULTS: The respective decreases of glycosaminoglycans (GAGs) and elasticity were 13.4 and 14.8% for group A and 30.4 and 32.6% for group B. The differences between group A and B and between each group and the control were statistically significant. The total collagen content was significantly lower in group B. CONCLUSIONS: The type of viable meniscal graft has an influence on the biochemical composition of the extracellular matrix (ECM) and biomechanical properties of the underlying tibial cartilage. A 1% decrease of glycosaminoglycan content is associated with a 1.1% decrease of cartilage elasticity. The average ratio of decrease of cartilage elasticity to that of the meniscus was 0.77 regardless of the type of meniscus graft. The viable allograft causes irreversible ECM disorder of the cartilage. Knowledge of the biochemical composition of the ECM meniscal grafts may serve as a predictor of their chondroprotective properties. PMID- 26560134 TI - Water deficit stress-induced changes in carbon and nitrogen partitioning in Chenopodium quinoa Willd. AB - MAIN CONCLUSION: Water deficit stress followed by re-watering during grain filling resulted in the induction of the ornithine pathway and in changes in Quinoa grain quality. The genetic diversity of Chenopodium quinoa Willd. (Quinoa) is accompanied by an outstanding environmental adaptability and high nutritional properties of the grains. However, little is known about the biochemical and physiological mechanisms associated with the abiotic stress tolerance of Quinoa. Here, we characterized carbon and nitrogen metabolic changes in Quinoa leaves and grains in response to water deficit stress analyzing their impact on the grain quality of two lowland ecotypes (Faro and BO78). Differences in the stress recovery response were found between genotypes including changes in the activity of nitrogen assimilation-associated enzymes that resulted in differences in grain quality. Both genotypes showed a common strategy to overcome water stress including the stress-induced synthesis of reactive oxygen species scavengers and osmolytes. Particularly, water deficit stress induced the stimulation of the ornithine and raffinose pathways. Our results would suggest that the regulation of C- and N partitioning in Quinoa during grain filling could be used for the improvement of the grain quality without altering grain yields. PMID- 26560135 TI - The Relationship between Anxiety Sensitivity and Posttraumatic Stress Disorder: What is the Impact of Nicotine Withdrawal? AB - OBJECTIVES: Anxiety sensitivity (AS) is related to the development and maintenance of posttraumatic stress disorder (PTSD) among cigarette smokers, and is also implicated in the amplification of acute nicotine withdrawal symptoms. The present study sought to examine the role of nicotine withdrawal in moderating the association between AS and PTSD symptom severity among a sample of treatment seeking smokers with PTSD. METHOD: Participants (n = 117) were enrolled in a randomized controlled trial for the treatment of PTSD and nicotine dependence. Cross-sectional data were randomly sampled from three different study time points. A series of multiple regression models were tested. RESULTS: Results revealed main effects of both AS and withdrawal severity on PTSD severity after controlling for gender, assessment time-point, negative affectivity, and biochemically verified smoking (expired carbon monoxide). The interaction of AS and withdrawal was also significant, and appeared to be specific to PTSD avoidance and hyperarousal symptoms. However, contrary to expectations, the association between AS and PTSD symptoms was only significant at relatively lower levels of nicotine withdrawal. CONCLUSIONS: These findings highlight the complex interplay between AS, nicotine withdrawal, and their synergistic effect in terms of the exacerbation of PTSD symptomology. PMID- 26560136 TI - Criticizing animal experimentation, at my peril. AB - Initiatives leading to even modest reduction in animal use at major U.S. universities are likely to continue to face strong opposition. At least, that's the conclusion the author draws from his efforts at Northwestern University. In fact, despite a growing body of evidence that animal-based research is flawed at best and misleading or un-scientific at worst its use is growing at Northwestern and elsewhere. Moreover, recent discoveries concerning animal consciousness and emotion have not led to notable improvements in the conditions in which AWA protected animals live at the Chicago vivarium. There, animals languish in featureless rooms or sterile cages without access to daylight and with little opportunity to express their natural behaviors and aptitudes. The writer's public exposure of these conditions led to a fierce backlash. Unless there is a significant change in laboratory and university culture, change will only come when the marketplace and funding agencies demand better and more reliable, non animal models for the testing of drug toxicity and effectiveness. PMID- 26560137 TI - Moving toward the ideal insulin for insulin pumps. AB - Advances in insulin formulations have been important for diabetes management and achieving optimal glycemic control. Rapid-acting insulin analogs provide a faster time-action profile than regular insulin and are approved for use in pumps. However, the need remains for therapy to deliver a more physiologic insulin profile. New insulin formulations and delivery methods are in development, with the aim of accelerating insulin absorption to accomplish ultra-fast-acting insulin time-action profiles. Furthermore, the integration of continuous glucose monitoring with insulin pump therapy enables on-going adjustment of insulin delivery to optimize glycemic control throughout the day and night. These technological and pharmacological advances are likely to facilitate the development of closed-loop pump systems (i.e., artificial pancreas), and improve glycemic control and quality of life for patients with diabetes. PMID- 26560138 TI - Accurate molecular imaging of small animals taking into account animal models, handling, anaesthesia, quality control and imaging system performance. AB - Small-animal imaging has become an important technique for the development of new radiotracers, drugs and therapies. Many laboratories have now a combination of different small-animal imaging systems, which are being used by biologists, pharmacists, medical doctors and physicists. The aim of this paper is to give an overview of the important factors in the design of a small animal, nuclear medicine and imaging experiment. Different experts summarize one specific aspect important for a good design of a small-animal experiment. PMID- 26560139 TI - Interventions to Improve Medication Adherence in Hypertensive Patients: Systematic Review and Meta-analysis. AB - This systematic review applied meta-analytic procedures to synthesize medication adherence interventions that focus on adults with hypertension. Comprehensive searching located trials with medication adherence behavior outcomes. Study sample, design, intervention characteristics, and outcomes were coded. Random effects models were used in calculating standardized mean difference effect sizes. Moderator analyses were conducted using meta-analytic analogues of ANOVA and regression to explore associations between effect sizes and sample, design, and intervention characteristics. Effect sizes were calculated for 112 eligible treatment-vs.-control group outcome comparisons of 34,272 subjects. The overall standardized mean difference effect size between treatment and control subjects was 0.300. Exploratory moderator analyses revealed interventions were most effective among female, older, and moderate- or high-income participants. The most promising intervention components were those linking adherence behavior with habits, giving adherence feedback to patients, self-monitoring of blood pressure, using pill boxes and other special packaging, and motivational interviewing. The most effective interventions employed multiple components and were delivered over many days. Future research should strive for minimizing risks of bias common in this literature, especially avoiding self-report adherence measures. PMID- 26560140 TI - Potential Cost-Effectiveness of Prenatal Distribution of Misoprostol for Prevention of Postpartum Hemorrhage in Uganda. AB - BACKGROUND: In settings where home birth rates are high, prenatal distribution of misoprostol has been advocated as a strategy to increase access to uterotonics during the third stage of labor to prevent postpartum hemorrhage (PPH). Our objective was to project the potential cost-effectiveness of this strategy in Uganda from both governmental (the relevant payer) and modified societal perspectives. METHODS AND FINDINGS: To compare prenatal misoprostol distribution to status quo (no misoprostol distribution), we developed a decision analytic model that tracked the delivery pathways of a cohort of pregnant women from the prenatal period, labor to delivery without complications or delivery with PPH, and successful treatment or death. Delivery pathway parameters were derived from the Uganda Demographic and Health Survey. Incidence of PPH, treatment efficacy, adverse event and case fatality rates, access to misoprostol, and health resource use and cost data were obtained from published literature and supplemented with expert opinion where necessary. We computed the expected incidence of PPH, mortality, disability adjusted life years (DALYs), costs and incremental cost effectiveness ratios (ICERs). We conducted univariate and probabilistic sensitivity analyses to examine robustness of our results. In the base-case analysis, misoprostol distribution lowered the expected incidence of PPH by 1.2% (95% credibility interval (CrI): 0.55%, 1.95%), mortality by 0.08% (95% CrI: 0.04%, 0.13%) and DALYs by 0.02 (95% CrI: 0.01, 0.03)." and "ICERs were US$181 (95% CrI: 81, 443) per DALY averted from a governmental perspective, and US$64 (95% CrI: -84, 260) per DALY averted from a modified societal perspective [corrected]. CONCLUSIONS: Prenatal distribution of misoprostol is potentially cost-effective in Uganda and should be considered for national-level scale up for prevention of PPH. PMID- 26560141 TI - NOD promoter-controlled AtIRT1 expression functions synergistically with NAS and FERRITIN genes to increase iron in rice grains. AB - Rice is a staple food for over half of the world's population, but it contains only low amounts of bioavailable micronutrients for human nutrition. Consequently, micronutrient deficiency is a widespread health problem among people who depend primarily on rice as their staple food. Iron deficiency anemia is one of the most serious forms of malnutrition. Biofortification of rice grains for increased iron content is an effective strategy to reduce iron deficiency. Unlike other grass species, rice takes up iron as Fe(II) via the IRON REGULATED TRANSPORTER (IRT) in addition to Fe(III)-phytosiderophore chelates. We expressed Arabidopsis IRT1 (AtIRT1) under control of the Medicago sativa EARLY NODULIN 12B promoter in our previously developed high-iron NFP rice lines expressing NICOTIANAMINE SYNTHASE (AtNAS1) and FERRITIN. Transgenic rice lines expressing AtIRT1 alone had significant increases in iron and combined with NAS and FERRITIN increased iron to 9.6 ug/g DW in the polished grains that is 2.2-fold higher as compared to NFP lines. The grains of AtIRT1 lines also accumulated more copper and zinc but not manganese. Our results demonstrate that the concerted expression of AtIRT1, AtNAS1 and PvFERRITIN synergistically increases iron in both polished and unpolished rice grains. AtIRT1 is therefore a valuable transporter for iron biofortification programs when used in combination with other genes encoding iron transporters and/or storage proteins. PMID- 26560142 TI - Local dependence in random graph models: characterization, properties and statistical inference. AB - Dependent phenomena, such as relational, spatial and temporal phenomena, tend to be characterized by local dependence in the sense that units which are close in a well-defined sense are dependent. In contrast with spatial and temporal phenomena, though, relational phenomena tend to lack a natural neighbourhood structure in the sense that it is unknown which units are close and thus dependent. Owing to the challenge of characterizing local dependence and constructing random graph models with local dependence, many conventional exponential family random graph models induce strong dependence and are not amenable to statistical inference. We take first steps to characterize local dependence in random graph models, inspired by the notion of finite neighbourhoods in spatial statistics and M-dependence in time series, and we show that local dependence endows random graph models with desirable properties which make them amenable to statistical inference. We show that random graph models with local dependence satisfy a natural domain consistency condition which every model should satisfy, but conventional exponential family random graph models do not satisfy. In addition, we establish a central limit theorem for random graph models with local dependence, which suggests that random graph models with local dependence are amenable to statistical inference. We discuss how random graph models with local dependence can be constructed by exploiting either observed or unobserved neighbourhood structure. In the absence of observed neighbourhood structure, we take a Bayesian view and express the uncertainty about the neighbourhood structure by specifying a prior on a set of suitable neighbourhood structures. We present simulation results and applications to two real world networks with 'ground truth'. PMID- 26560143 TI - Absolute Quantification of Endogenous Ras Isoform Abundance. AB - Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with >=260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS>=HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID- 26560144 TI - The use of medication in selective mutism: a systematic review. AB - Despite limited evidence, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are used to reduce symptoms of selective mutism (SM) in children unresponsive to psychosocial interventions. We review existing evidence for the efficacy of these medications, limitations of the literature, and resulting treatment considerations. Bibliographic searches were conducted in Medline, Embase, PsycInfo, Web of Science and Cochrane up to June 2015. Two reviewers independently sought studies of children with SM as primary psychiatric diagnosis, which reported response to medication treatment. Abstracts were limited to those reporting original data. Two reviewers independently assessed the ten papers reporting on >2 subjects regarding study design, key results, and limitations. Heterogeneity of designs mandated a descriptive summary. Symptomatic improvement was found for 66/79 children treated with SSRIs and 4/4 children treated with phenelzine. Only 3/10 studies had unmedicated comparison groups and only two were double-blinded. This review may be affected by publication bias, missed studies, and variability of outcome measures in included studies. Although there is some evidence for symptomatic improvement in SM with medication, especially SSRIs, it is limited by small numbers, lack of comparative trials, lack of consistent measures, and lack of consistent reporting on tolerability. The clinician must weigh this paucity of evidence against the highly debilitating nature of SM, and its adverse effects on the development of those children whose progress with psychosocial interventions is limited or very slow. Studies of optimal dosage and timing of medications in relation to psychosocial treatments are also needed. PMID- 26560145 TI - Dual PI3K/mTOR inhibitor BEZ235 exerts extensive antitumor activity in HER2 positive gastric cancer. AB - BACKGROUND: To investigate the in vitro and in vivo antitumor activity of dual PI3K/mTOR inhibitor BEZ235 (NVP-BEZ235) in HER2-positive gastric cancer. METHODS: HER2-positive breast cancer cell line (BT474), HER2-positive (NCI-N87 and SNU216), and HER2-negative (MKN45) gastric cancer cell lines were used in this study. Cell viability, cell cycle, and HER2 downstream signaling pathways were analyzed using the MTS assay, flow cytometry, and western blotting, respectively. For the in vivo experiments, HER2-positive gastric cancer patient-derived xenografts were treated with BEZ235 to assess its antitumor activity. RESULTS: The sensitivity of trastuzumab in BT474 cells was higher than that for NCI-N87 and SNU216 cells, which may be partially attributed to continuously active HER2 downstream signaling pathway. BEZ235 inhibited the proliferation of NCI-N87 and SNU216 cells in vitro in a dose-dependent manner by inducing the cell cycle arrest at the G1 phase. BEZ235 demonstrated greater inhibitory effects than trastuzumab, a unique targeted drug, in both the in vitro and in vivo set of experiments. Additionally, our results indicate that BEZ235 displayed some synergism with trastuzumab. BEZ235 exhibited its antitumor activity in gastric cancer by inhibiting important HER2 downstream signaling pathways, as indicated by the inhibition of phosphorylated AKT and S6. CONCLUSION: The present study has demonstrated, for the first time, the antitumor activity of BEZ235 against HER2 positive gastric cancer in patient-derived xenografts, as well its synergistic interaction with trastuzumab. These important findings can be utilized to facilitate the design of future clinical trials. PMID- 26560146 TI - New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials. AB - INTRODUCTION: As currently used, the Alzheimer's Disease Assessment Scale Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer's disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity. METHODS: Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect. RESULTS: The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect. CONCLUSIONS: The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer's disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease modifying treatments. PMID- 26560147 TI - Human Genetic Relevance and Potent Antitumor Activity of Heat Shock Protein 90 Inhibition in Canine Lung Adenocarcinoma Cell Lines. AB - BACKGROUND: It has been an open question how similar human and canine lung cancers are. This has major implications in availability of human treatments for dogs and in establishing translational models to test new therapies in pet dogs. The prognosis for canine advanced lung cancer is poor and new treatments are needed. Heat shock protein 90 (HSP90) is an ATPase-dependent molecular chaperone ubiquitously expressed in eukaryotic cells. HSP90 is essential for posttranslational conformational maturation and stability of client proteins including protein kinases and transcription factors, many of which are important for the proliferation and survival of cancer cells. We investigated the activity of STA-1474, a HSP90 inhibitor, in two canine lung cancer cell lines, BACA and CLAC. RESULTS: Comparative genomic hybridization analysis of both cell lines revealed genetic relevance to human non-small cell lung cancer. STA-1474 inhibited growth and induced apoptosis of both cell lines in a dose- and time dependent manner. The ICs50 after 72 h treatment with STA-1474 were 0.08 and 0.11 MUM for BACA and CLAC, respectively. When grown as spheroids, the IC50 of STA 1474 for BACA cells was approximately two-fold higher than when grown as a monolayer (0.348 MUM vs. 0.168 MUM), whereas CLAC spheroids were relatively drug resistant. Treatment of tumor-stromal fibroblasts with STA-1474 resulted in a dose-dependent decrease in their relative cell viability with a low IC50 of 0.28 MUM. CONCLUSIONS: Here we first established that lung adenocarcinoma in people and dogs are genetically and biochemically similar. STA1474 demonstrated biological activity in both canine lung cancer cell lines and tumor-stromal fibroblasts. As significant decreases in relative cell viability can be achieved with nanomolar concentrations of STA-1474, investigation into the clinical efficacy of this drug in canine lung cancer patients is warranted. PMID- 26560148 TI - Changes of Laryngeal Mobility and Symptoms Following Thyroid Surgery: 6-Month Follow-Up. AB - OBJECTIVE: Swallowing disorders are frequent complaints after thyroidectomy even in the absence of recurrent laryngeal nerve palsy. The aim of this study was to assess different symptoms in relation to laryngeal mobility following thyroidectomy. MATERIALS AND METHODS: 53 patients (mean age 52.4 +/- 12.5 years; 36 female) with initially benign diagnosis and intact recurrent nerve functioning were prospectively evaluated. Laryngeal movement was analyzed by ultrasound preoperatively and 1, 3, and 6 months postoperatively. In addition, a dysphagia and voice-specific quality-of-life questionnaire was used. RESULTS: Mean laryngeal movement differed between genders preoperatively and postoperatively resulting in a recovery predominantly in women (reduction of mobility at 1, 3, and 6 months postoperatively in females was 6.0, 3.7, and 1.5 mm, and in males 13.8, 11.7, and 10.3 mm, respectively). Mainly, women reported hoarseness (9 females) and cervical discomfort (7 females, 3 males) 1 month postoperatively. After 6 months, these complaints resolved (cervical discomfort 1 female). CONCLUSION: Laryngeal mobility was significantly impaired postoperatively and only females revealed a recovery close to baseline after 6 months. Although showing only a small grade of recovery of laryngeal movement, subjective clinical symptoms were found to be rare in male patients. PMID- 26560149 TI - Survival in Resected Stage II Colorectal Cancer Is Dependent on Tumor Depth, Vascular Invasion, Postoperative CEA Level, and The Number of Examined Lymph Nodes. AB - BACKGROUND: The aim of the present study was to determine which aspects of tumor histology influence postoperative early relapse and overall survival rates after radical resection of stage II colorectal cancer (CRC). METHODS: Data were collected for 425 patients with stage II CRC who began treatment at a single institution between January 2006 and October 2013. All the enrolled patients were followed up on until death or until December 2014. Clinically significant factors affecting postoperative early relapse and overall survival rates were analyzed. RESULTS: Using a multivariate analysis, tumor invasion depth (P = 0.008), vascular invasion (P = 0.029), postoperative carcinoembryonic antigen (CEA) level (P = 0.001), and retrieval of less than 12 lymph nodes (P = 0.002) were found to be independent predictors for postoperative early relapse. A combination of tumor invasion depth, vascular invasion, postoperative CEA level, and number of lymph nodes retrieved showed that the greater the number of predictors involved, the higher the likelihood of postoperative early relapse and the poorer the overall survival. CONCLUSIONS: This study revealed that T4 invasion, vascular invasion, postoperative CEA level, and the number of examined lymph nodes may significantly affect the prognosis of stage II CRC patients after radical resection. The risks of postoperative early relapse and worse clinical outcome increase in proportion to the values of these four parameters. PMID- 26560150 TI - Trends in Prevalence of Thyroid Cancer Over Three Decades: A Retrospective Cohort Study of 17,526 Surgical Patients. AB - INTRODUCTION: Thyroid cancer (TC) incidence has been increasing in recent years. The aim of this study was to investigate our institution-based estimates of operative volumes for TC over the last three decades. MATERIALS AND METHODS: This was a retrospective cohort study of patients undergoing thyroid surgery at our institution. Patient characteristics were reviewed in three subgroups: Group I (treated in 1981-1986), Group II (treated in 1987-2002), and Group III (treated in 2003-2012). RESULTS: TC was diagnosed in 1578/17,526 (9.0%) thyroid operations. Incidence of TC increased from 3.7% in Group I to 10.4% in Group III (p < 0.001). Incidence of papillary TC increased form 40.6% in Group I to 81.3% in Group III (p < 0.001). In the latter group, 23.5% of all papillary TCs were diagnosed in patients with Hashimoto's disease. Meanwhile, incidence of anaplastic TC decreased from 16.2% in Group I to 2.1% in Group III patients (p < 0.001). pT1 tumors were diagnosed in 8.1% Group I and 54.8% Group III (p < 0.001), whereas pT4 tumors were identified in 40.5% Group I, 2.4% Group II, and 0.84% Group III subjects (p < 0.001). pT3 tumors were found in 51.6% Group I, whereas multifocal papillary TCs were found in 15.7% Group III patients, the latter with a higher prevalence of pN1 stage (p < 0.001). CONCLUSIONS: The following trends in surgical volume for TC were identified throughout the study period: a fivefold increase of thyroid operations for TC, a threefold increase in incidence of papillary TC, and an eightfold decrease in incidence of anaplastic TC. It is of interest that a significant increase in incidence of multifocal papillary TC in young female patients with Hashimoto's disease was found over time. PMID- 26560151 TI - Optimising Breast Conservation Treatment for Multifocal and Multicentric Breast Cancer: A Worthwhile Endeavour? AB - BACKGROUND: Breast conservation treatment (BCT) is an accepted treatment modality for early breast cancer. However, multifocal and multicentric breast cancer (MFMCBC) is a relative contraindication to BCT. This study was performed to compare BCT rates in MFMCBC and unifocal tumours and its outcomes. METHODS: A retrospective analysis was performed for patients with breast malignancies who underwent operative treatment between 2009 and 2011. Successful BCT was defined as the ability to obtain clear margins for all tumour foci through a single incision with acceptable resultant cosmesis. RESULTS: A total of 160 patients were analysed, of which 40 were MFMCBC. Thirty-four of the 40 patients with MFMCBC underwent BCT (85 %). After a mean follow-up period of 55 months, there were no local recurrences in patients with MFMCBC. CONCLUSION: BCT was achieved in 85 % of the patients with MFMCBC in this cohort without evidence of poorer local control. Further investigation is needed to confirm this finding for its potential contribution to improved survival outcomes. PMID- 26560152 TI - Liver Exposure Using Sterile Glove Pouch During Laparoscopic Right Liver Surgery in Hepatocellular Carcinoma Patients. AB - BACKGROUND: Although laparoscopy is widely accepted for liver resection, lesions in the posterior and superior segments and deep region in the right lobe are difficult for visualization during laparoscopic liver resection (LLR). In this study, we aim examine the effects of using sterile gloves (SG) pouch padding during LLR. METHODS: Forty-two hepatocellular carcinoma (HCC) patients were included in our study. We performed LLR using SG (n = 24, SG group) and without SG during LLR (n = 18, NSG). We also compared the time of various procedures, blood loss, and liver function between the two groups. RESULTS: We did not observe any major complications or death in all patients. The time of liver parenchyma transection and portal triad clamping in SG group is significantly shorter than those in NSG group (30.29 +/- 5.55 vs. 39.00 +/- 3.68 min p < .001 for liver parenchyma transection, 23.00 +/- 5.60 vs. 31.60 +/- 5.03 min p < .001 for portal triad clamping). Blood loss in SG group (162.91 +/- 90.91 ml) was significantly lower than in NSG group (236.66 +/- 101.67 ml p = .024). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased one day after LLR, and decreased to normal level on day 7 after LLR in both groups. CONCLUSIONS: Our data suggests that a sterile glove pouch could enhance exposure in surgical field, which results in decrease in blood loss and procedure time. More studies with large sample size, large tumor size, and longer follow-up are needed. PMID- 26560153 TI - Evaluation of Major Online Diabetes Risk Calculators and Computerized Predictive Models. AB - Classical paper-and-pencil based risk assessment questionnaires are often accompanied by the online versions of the questionnaire to reach a wider population. This study focuses on the loss, especially in risk estimation performance, that can be inflicted by direct transformation from the paper to online versions of risk estimation calculators by ignoring the possibilities of more complex and accurate calculations that can be performed using the online calculators. We empirically compare the risk estimation performance between four major diabetes risk calculators and two, more advanced, predictive models. National Health and Nutrition Examination Survey (NHANES) data from 1999-2012 was used to evaluate the performance of detecting diabetes and pre-diabetes. American Diabetes Association risk test achieved the best predictive performance in category of classical paper-and-pencil based tests with an Area Under the ROC Curve (AUC) of 0.699 for undiagnosed diabetes (0.662 for pre-diabetes) and 47% (47% for pre-diabetes) persons selected for screening. Our results demonstrate a significant difference in performance with additional benefits for a lower number of persons selected for screening when statistical methods are used. The best AUC overall was obtained in diabetes risk prediction using logistic regression with AUC of 0.775 (0.734) and an average 34% (48%) persons selected for screening. However, generalized boosted regression models might be a better option from the economical point of view as the number of selected persons for screening of 30% (47%) lies significantly lower for diabetes risk assessment in comparison to logistic regression (p < 0.001), with a significantly higher AUC (p < 0.001) of 0.774 (0.740) for the pre-diabetes group. Our results demonstrate a serious lack of predictive performance in four major online diabetes risk calculators. Therefore, one should take great care and consider optimizing the online versions of questionnaires that were primarily developed as classical paper questionnaires. PMID- 26560154 TI - A Cognitive Neural Architecture Able to Learn and Communicate through Natural Language. AB - Communicative interactions involve a kind of procedural knowledge that is used by the human brain for processing verbal and nonverbal inputs and for language production. Although considerable work has been done on modeling human language abilities, it has been difficult to bring them together to a comprehensive tabula rasa system compatible with current knowledge of how verbal information is processed in the brain. This work presents a cognitive system, entirely based on a large-scale neural architecture, which was developed to shed light on the procedural knowledge involved in language elaboration. The main component of this system is the central executive, which is a supervising system that coordinates the other components of the working memory. In our model, the central executive is a neural network that takes as input the neural activation states of the short term memory and yields as output mental actions, which control the flow of information among the working memory components through neural gating mechanisms. The proposed system is capable of learning to communicate through natural language starting from tabula rasa, without any a priori knowledge of the structure of phrases, meaning of words, role of the different classes of words, only by interacting with a human through a text-based interface, using an open ended incremental learning process. It is able to learn nouns, verbs, adjectives, pronouns and other word classes, and to use them in expressive language. The model was validated on a corpus of 1587 input sentences, based on literature on early language assessment, at the level of about 4-years old child, and produced 521 output sentences, expressing a broad range of language processing functionalities. PMID- 26560155 TI - Beyond antidoping and harm minimisation: a stakeholder-corporate social responsibility approach to drug control for sport. AB - Debate about the ethics of drug control in sport has largely focused on arguing the relative merits of the existing antidoping policy or the adoption of a health based harm minimisation approach. A number of ethical challenges arising from antidoping have been identified, and a number of, as yet, unanswered questions remain for the maturing ethics of applying harm minimisation principles to drug control for sport. This paper introduces a 'third approach' to the debate, examining some implications of applying a stakeholder theory of corporate social responsibility (CSR) to the issue of doping in sport. The introduction of the stakeholder-CSR model creates an opportunity to challenge the two dominant schools by enabling a different perspective to contribute to the development of an ethically robust drug control for sport. PMID- 26560156 TI - Understanding (and) consent: a response to MacKay. PMID- 26560158 TI - Evaluating the effect of health warnings in influencing Australian smokers' psychosocial and quitting behaviours using fuzzy causal network. AB - This paper explores the application of fuzzy causal networks (FCNs) to evaluating effect of health warnings in influencing Australian smokers' psychosocial and quitting behaviour. The sample data used in this study are selected from the International Tobacco Control Policy Evaluation Survey project. Our research findings have demonstrated that new health warnings implemented in Australia have obvious impacts on smokers' psychosocial and quitting behaviours. FCN is a useful framework to investigate such impacts that overcome the limitation of using traditional statistical techniques, such as linear regression and logistics regression, to analyse non-linear data. PMID- 26560157 TI - Factors associated with the receipt of fertility preservation services along the decision-making pathway in young Canadian female cancer patients. AB - PURPOSE: This study investigated the factors associated with the receipt of fertility preservation (FP) services along the decision-making pathway in young Canadian female cancer patients. The roles of the oncologists were examined. METHODS: A total of 188 women who were diagnosed with cancer between the ages of 18-39 after the year 2000 and had finished active cancer treatment by the time of the survey (2012-2013) participated in the study. Logistic regression models and Pearson chi (2) tests were used for analyses. RESULTS: The mean ages of participants at diagnosis and at survey time were 30.2 (SD = 3.7) and 33.9 (SD = 5.9). One quarter (n = 45, 23.9 %) did not recall having a fertility discussion with their oncologists. Of the three quarters who had a fertility discussion (n = 143, 76.1 %), discussions were equally initiated by oncologists (n = 71) and patients (n = 72). Of the 49 women (26 %) who consulted a fertility specialist, 17 (9 %) underwent a FP procedure. Fertility concern at diagnosis was the driving force of the receipt of FP services at all decision points. Our findings suggest that not only was the proactive approach of oncologists in initiating a fertility discussion important, the quality of the discussion was equally critical in the decision-making pathway. CONCLUSIONS: Oncologists play a pivotal role in the provision of fertility services in that they are not only gate keepers, knowledge brokers, and referral initiators of FP consultation, but also they are catalysts in supporting cancer patients making important FP decision in conjunction with the consultation provided by a fertility specialist. PMID- 26560159 TI - Enterprises and challenges in diagnostics for precision medicine: an interview with Eddie Blair. AB - Interview with Dr Eddie Blair, PhD, by Claire Raison (Commissioning Editor) Dr Eddie Blair is Managing Director of Integrated Medicines Ltd (Cambridge, UK), a company he formed in 2003 to enable precision medicine by combining diagnostic testing with new and existing medicines. Dr Blair has raised angel and private equity investments in excess of L12 million, has published over 40 primary peer reviewed papers, including a series on companion diagnostic valuation, and is named inventor on at least 12 patents. Dr Blair is a member of the Editorial Advisory Board of Expert Review of Molecular Diagnostics and speaks to the Commissioning Editor here about entrepreneurship, obstacles and potential of introducing diagnostics innovations into routine clinical practice. PMID- 26560160 TI - Do we really know how much we are feeding our patients? AB - BACKGROUND: Nutrition support is important in critical illness, and accurate recording is particularly important to determine whether nutritional goals are met both from a caloric and volume perspective. OBJECTIVE: To assess accuracy of enteral feeding records, to increase nursing education and to improve nutritional documentation. METHODS: An uncontrolled, prospective, pre- and post-intervention study was completed as part of a quality improvement initiative. This study was performed in a 950-bed university hospital (Philadelphia, Pennsylvania) and focused in a 25-bed, closed intensive care unit (ICU) with a multidisciplinary rounding team of intensivist, nurse, pharmacist, dietitian and respiratory therapist. Nurse researchers reviewed 188 patient electronic medical records (EMR) and compared the data to volume data saved on enteral feeding pump. Data analysis revealed inconsistencies between the pump readings and EMR. The need for a prospective intervention was recognized and implementation of this intervention included pump calibration and teaching modules aimed at improving enteral feeding protocols. During post-intervention, another 234 records were reviewed. RESULTS: The intervention of an education program reduced the documented discrepancy between the pump readings and charted volumes from 44 to 33%. A correlation analysis also showed a tighter relationship post-intervention (rpost = 0.84 vs. rpre = 0.76, both had a p < 0.01). CONCLUSION: This study highlights the importance of accurate nutritional monitoring in the ICU and demonstrates that educational interventions can improve enteral feeding protocols. Pump calibrations, frequent interrogation and vigilant nutritional documentation can improve enteral nutrition delivery. Future studies are needed to determine if the effects are sustainable and if further education will further improve documentation and delivery. PMID- 26560161 TI - [Ophthalmic care in the Second World War, 75 years after]. PMID- 26560162 TI - Current interpretation of optical coherence tomography in the posterior pole. AB - OBJECTIVE: To review the literature in order to describe the current nomenclature for the interpretation of retinal images of optical coherence tomography (OCT) in the macular area. METHODS: A comprehensive literature search was conducted in the major biomedical databases since the introduction of OCT in ophthalmological field. RESULTS: Quantitative variations of central macular thickness and proper terminology used throughout the years are directly related to the technology and equipment used. CONCLUSIONS: The current nomenclature of normal macular architecture represented in vivo on spectral domain OCT technology provides a clear and valid anatomical interpretation that can be applied, not only in research, but also in everyday practice. PMID- 26560163 TI - Human tear metabolome. PMID- 26560164 TI - Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis. AB - CLINICAL CASE: The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. DISCUSSION: When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. PMID- 26560165 TI - Visual involvement in foreign-body intestinal perforations. AB - INTRODUCTION: Intestinal perforation due to ingestion of a foreign body accounts for 21% of the total in our hospital. METHODS: All cases of intestinal perforation due to foreign body ingestion occurring since 1990 were collected (29 cases), and the visual characteristics of these patients were analysed. RESULTS AND DISCUSSION: The mean age was 74.2 years (all of them presbyopic) with the majority being female (1.9:1). The most frequently ingested foreign body was fish bone (55%). The corrected near visual acuity obtained a mean value of 0.73, while the real visual accuity (only one of them wore glasses to eat) was 0.145. Four patients (20%) had only one eye, and the TNO test was positive in only 12 (60%). At least 13 (65%) had some degree of cataract. CONCLUSIONS: Improving near visual acuity with either early cataract surgery and/or multifocal intraocular lenses may decrease the number of gastrointestinal perforations. PMID- 26560166 TI - Birdshot-like retinochoroidopathy as onset of Whipple's disease. PMID- 26560167 TI - Treatment of ophthalmological diseases in the 16th century. An analysis of the medicinal plants from new Spain published by Francisco Hernandez. PMID- 26560168 TI - Deceiving the on-off cells: Historic evolution of our comprehension of the way animals camouflage themselves. PMID- 26560169 TI - From physiological vascular tortuosity to the tortuositas vasorum retinae. PMID- 26560170 TI - Tazarotene foam, 0.1%, for the treatment of acne. AB - INTRODUCTION: Acne is a common skin condition of the pilosebaceous units that affects the young and old, ranges from moderate to severe and can be treated with an array of options. Topical retinoids are the initial treatment for acne due to their ability to treat comedones, the starting point of acne. AREAS COVERED: Tazarotene is a topical retinoid available as a cream, gel and foam. Tazarotene 0.1% foam was FDA approved in 2012 for the treatment of acne in patients ages >=12 and is the first foam topical retinoid on the market. Phase I and III trials support the efficacy and safety of tazarotene foam for acne. EXPERT OPINION: The foam vehicles may increase compliance and satisfaction in some patients and as retinoids are commonly first line acne treatments, this new topical retinoid foam may be a useful option for some acne patients. PMID- 26560171 TI - T cell immunity to dengue virus and implications for vaccine design. AB - Dengue virus infections are increasing at an alarming rate in many tropical and subtropical countries and represent, in some of these areas, a leading cause of hospitalization and death among children. The lack of a clear definition of the correlates of protection from severe dengue disease represents a major hurdle for vaccine development. In particular, the role of T lymphocytes during dengue infection remains unclear and there is evidence suggesting that these cells may be important for both protective immunity and/or immunopathology. In this review we discuss the findings that support a protective role of T cells versus those supporting their involvement in pathogenesis. A better understanding of T cell immunity is urgently needed for the development of safe and efficacious vaccines. PMID- 26560172 TI - Psychological therapies for preventing seasonal affective disorder. AB - BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on psychological therapies as preventive interventions. OBJECTIVES: To assess the efficacy and safety of psychological therapies (in comparison with no treatment, other types of psychological therapy, second-generation antidepressants (SGAs), light therapy, melatonin or agomelatine or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We conducted a search of the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we planned to include randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non randomised studies. We planned to include studies that compared psychological therapy versus any other type of psychological therapy, placebo, light therapy, SGAs, melatonin, agomelatine or lifestyle changes. We also intended to compare psychological therapy in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors planned to independently extract data and assess risk of bias. We planned to pool data for meta-analysis when participant groups were similar and when studies assessed the same treatments versus the same comparator and provided similar definitions of outcome measures over a similar duration of treatment; however, we included no studies. MAIN RESULTS: We identified 2986 citations through electronic searches and reviews of reference lists after de-duplication of search results. We excluded 2895 records during title and abstract review and assessed 91 articles at full-text review for eligibility. We found no controlled studies on use of psychological therapy to prevent SAD and improve patient-centred outcomes in adults with a history of SAD. AUTHORS' CONCLUSIONS: Presently, there is no methodologically sound evidence available to indicate whether psychological therapy is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD. Randomised controlled trials are needed to compare different types of psychological therapies and to compare psychological therapies versus placebo, light therapy, SGAs, melatonin, agomelatine or lifestyle changes for prevention of new depressive episodes in patients with a history of winter-type SAD. PMID- 26560173 TI - Melatonin and agomelatine for preventing seasonal affective disorder. AB - BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD in the United States ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions. OBJECTIVES: To assess the efficacy and safety of agomelatine and melatonin (in comparison with each other, placebo, second generation antidepressants, light therapy, psychological therapy or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We conducted a search of the Specialised Register of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we planned to include randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second generation antidepressant (SGA), light therapy, psychological therapies or lifestyle changes. We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors planned to independently extract data and assess risk of bias of included studies. We planned to pool data for meta-analysis when participant groups were similar and when studies assessed the same treatments by using the same comparator and presented similar definitions of outcome measures over a similar duration of treatment; however, we identified no studies for inclusion. MAIN RESULTS: We identified 2986 citations through electronic searches and reviews of reference lists after de-duplication of search results. We excluded 2895 records during title and abstract review and assessed 91 articles at full-text level for eligibility. We identified no controlled studies on use of melatonin and agomelatine to prevent SAD and to improve patient-centred outcomes among adults with a history of SAD. AUTHORS' CONCLUSIONS: No available methodologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient centred outcomes among adults with a history of SAD. Lack of evidence clearly shows the need for well-conducted, controlled studies on this topic. A well conducted RCT of melatonin or agomelatine for prevention of SAD would assess the comparative benefits and risks of these interventions against others currently used to treat the disorder. PMID- 26560175 TI - A New Brachylophosaurin Hadrosaur (Dinosauria: Ornithischia) with an Intermediate Nasal Crest from the Campanian Judith River Formation of Northcentral Montana. AB - BACKGROUND: Brachylophosaurini is a clade of hadrosaurine dinosaurs currently known from the Campanian (Late Cretaceous) of North America. Its members include: Acristavus gagslarsoni, which lacks a nasal crest; Brachylophosaurus canadensis, which possesses a flat paddle-shaped nasal crest projecting posteriorly over the dorsal skull roof; and Maiasaura peeblesorum, which possesses a dorsally projecting nasofrontal crest. Acristavus, from the lower Two Medicine Formation of Montana (~81-80 Ma), is hypothesized to be the ancestral member of the clade. Brachylophosaurus specimens are from the middle Oldman Formation of Alberta and equivalent beds in the Judith River Formation of Montana; the upper Oldman Formation is dated 77.8 Ma. METHODOLOGY/PRINCIPAL FINDINGS: A new brachylophosaurin hadrosaur, Probrachylophosaurus bergei (gen. et sp. nov.) is described and phylogenetically analyzed based on the skull and postcranium of a large individual from the Judith River Formation of northcentral Montana (79.8 79.5 Ma); the horizon is equivalent to the lower Oldman Formation of Alberta. Cranial morphology of Probrachylophosaurus, most notably the nasal crest, is intermediate between Acristavus and Brachylophosaurus. In Brachylophosaurus, the nasal crest lengthens and flattens ontogenetically, covering the supratemporal fenestrae in large adults. The smaller nasal crest of Probrachylophosaurus is strongly triangular in cross section and only minimally overhangs the supratemporal fenestrae, similar to an ontogenetically earlier stage of Brachylophosaurus. Sutural fusion and tibial osteohistology reveal that the holotype of Probrachylophosaurus was relatively more mature than a similarly large Brachylophosaurus specimen; thus, Probrachylophosaurus is not simply an immature Brachylophosaurus. CONCLUSIONS/SIGNIFICANCE: The small triangular posteriorly oriented nasal crest of Probrachylophosaurus is proposed to represent a transitional nasal morphology between that of a non-crested ancestor such as Acristavus and the large flat posteriorly oriented nasal crest of adult Brachylophosaurus. Because Probrachylophosaurus is stratigraphically and morphologically intermediate between these taxa, Probrachylophosaurus is hypothesized to be an intermediate member of the Acristavus-Brachylophosaurus evolutionary lineage. PMID- 26560176 TI - Superior Photostability and Photocatalytic Activity of ZnO Nanoparticles Coated with Ultrathin TiO2 Layers through Atomic-Layer Deposition. AB - Atomic-layer deposition (ALD) is a thin-film growth technology that allows for conformal growth of thin films with atomic-level control over their thickness. Although ALD is successful in the semiconductor manufacturing industry, its feasibility for nanoparticle coating has been less explored. Herein, the ALD coating of TiO2 layers on ZnO nanoparticles by employing a specialized rotary reactor is demonstrated. The photocatalytic activity and photostability of ZnO nanoparticles coated with TiO2 layers by ALD and chemical methods were examined by the photodegradation of Rhodamine B dye under UV irradiation. Even though the photocatalytic activity of the presynthesized ZnO nanoparticles is higher than that of commercial P25 TiO2 nanoparticles, their activity tends to decline due to severe photocorrosion. The chemically synthesized TiO2 coating layer on ZnO resulted in severely declined photoactivity despite the improved photostability. However, ultrathin and conformal ALD TiO2 coatings (~ 0.75-1.5 nm) on ZnO improved its photostability without degradation of photocatalytic activity. Surprisingly, the photostability is comparable to that of pure TiO2, and the photocatalytic activity to that of pure ZnO. PMID- 26560174 TI - Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro. AB - BACKGROUND: Antibiotic resistance genes can be targeted by antisense agents, which can reduce their expression and thus restore cellular susceptibility to existing antibiotics. Antisense inhibitors can be gene and pathogen specific, or designed to inhibit a group of bacteria having conserved sequences within resistance genes. Here, we aimed to develop antisense peptide nucleic acids (PNAs) that could be used to effectively restore susceptibility to beta-lactams in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP). RESULTS: Antisense PNAs specific for conserved regions of the mobilisable gene mecA, and the growth essential gene, ftsZ, were designed. Clinical MRSA and MRSP strains of high oxacillin resistance were treated with PNAs and assayed for reduction in colony forming units on oxacillin plates, reduction in target gene mRNA levels, and cell size. Anti-mecA PNA at 7.5 and 2.5 MUM reduced mecA mRNA in MRSA and MRSP (p < 0.05). At these PNA concentrations, 66 % of MRSA and 92 % of MRSP cells were killed by oxacillin (p < 0.01). Anti-ftsZ PNA at 7.5 and 2.5 MUM reduced ftsZ mRNA in MRSA and MRSP, respectively (p <= 0.05). At these PNA concentrations, 86 % of MRSA cells and 95 % of MRSP cells were killed by oxacillin (p < 0.05). Anti-ftsZ PNAs resulted in swelling of bacterial cells. Scrambled PNA controls did not affect MRSA but sensitized MRSP moderately to oxacillin without affecting mRNA levels. CONCLUSIONS: The antisense PNAs effects observed provide in vitro proof of concept that this approach can be used to reverse beta-lactam resistance in staphylococci. Further studies are warranted as clinical treatment alternatives are needed. PMID- 26560177 TI - Longitudinal Evaluation of Residual Cortical and Subcortical Motor Evoked Potentials in Spinal Cord Injured Rats. AB - We have applied transcranial electrical stimulation to rats with spinal cord injury and selectively tested the motor evoked potentials (MEPs) conveyed by descending motor pathways with cortical and subcortical origin. MEPs were elicited by electrical stimulation to the brain and recorded on the tibialis anterior muscles. Stimulation parameters were characterized and changes in MEP responses tested in uninjured rats, in rats with mild or moderate contusion, and in animals with complete transection of the spinal cord. All injuries were located at the T8 vertebral level. Two peaks, termed N1 and N2, were obtained when changing from single pulse stimulation to trains of 9 pulses at 9 Hz. Selective injuries to the brain or spinal cord funiculi evidenced the subcortical origin of N1 and the cortical origin of N2. Animals with mild contusion showed small behavioral deficits and abolished N1 but maintained small amplitude N2 MEPs. Substantial motor deficits developed in rats with moderate contusion, and these rats had completely eliminated N1 and N2 MEPs. Animals with complete cord transection had abolished N1 and N2 and showed severe impairment of locomotion. The results indicate the reliability of MEP testing to longitudinally evaluate over time the degree of impairment of cortical and subcortical spinal pathways after spinal cord injuries of different severity. PMID- 26560178 TI - Multiscale and multiresolution modeling of shales and their flow and morphological properties. AB - The need for more accessible energy resources makes shale formations increasingly important. Characterization of such low-permeability formations is complicated, due to the presence of multiscale features, and defies conventional methods. High quality 3D imaging may be an ultimate solution for revealing the complexities of such porous media, but acquiring them is costly and time consuming. High-quality 2D images, on the other hand, are widely available. A novel three-step, multiscale, multiresolution reconstruction method is presented that directly uses 2D images in order to develop 3D models of shales. It uses a high-resolution 2D image representing the small-scale features to reproduce the nanopores and their network, a large scale, low-resolution 2D image to create the larger-scale characteristics, and generates stochastic realizations of the porous formation. The method is used to develop a model for a shale system for which the full 3D image is available and its properties can be computed. The predictions of the reconstructed models are in excellent agreement with the data. The method is, however, quite general and can be used for reconstructing models of other important heterogeneous materials and media. Two biological examples and from materials science are also reconstructed to demonstrate the generality of the method. PMID- 26560179 TI - Incidentally-detected t(9;22)(q34;q11)/BCR-ABL1- positive clone developing into chronic phase chronic myeloid leukaemia after four years of dormancy. PMID- 26560180 TI - aEEG and cEEG: Two complementary techniques to assess seizures and encephalopathy in neonates: Editorial on "Amplitude-integrated EEG for detection of neonatal seizures: A systematic review" by Rakshasbhuvankar et al. PMID- 26560182 TI - A Simple and Rapid Test-card Method to Detect Hepatitis B Surface Antigen and Antibody: Potential Application in Young Children and Infants. AB - BACKGROUND: Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were conventionally determined by enzyme immunoassays. We aimed to apply a rapid, simple, and accurate method to detect HBsAg and its antibody. METHODS: We collected 1463 serum samples from healthy volunteers, hepatitis B carriers, and children of HBsAg-positive mothers. The test card that we examined is a chromatographic immunoassay for the qualitative detection of either HBsAg or anti-HBs. We then compared the results of the test card to the results of the conventional enzyme-immunoassay method, which is regarded as a standard. RESULTS: In the use of the test card to check HBsAg, the sensitivity was 88.8% and the specificity was 100%. The median hepatitis B virus viral load was significantly higher in the true-positive group [10(3.71) copies/mL (range, 10(2)-10(9.03) copies/mL)] than in the false-negative group [10(2) copies/mL (range, 10(2) 10(3.26) copies/mL)] (p = 0.005). In those who were younger than 2 years, the diagnostic accuracy of the HBsAg test card was 100%. Then, 1272 samples were tested for anti-HBs rapid test card. The sensitivity was 91.8% and the specificity was 96.5%. The median anti-HBs titer was significantly higher in the true-positive group (295.8 mIU/mL) than in the false-negative group (42.3 mIU/mL; p < 0.001). CONCLUSION: Because of (1) the limited amount of blood sample required and (2) most of the young hepatitis B virus carriers having high viremia, and no concerns of false negativity, the test card is a good rapid screening tool for the detection of HBsAg and anti-HBs in pediatric group. PMID- 26560183 TI - Effects of Breast Milk and Vanilla Odors on Premature Neonate's Heart Rate and Blood Oxygen Saturation During and After Venipuncture. AB - BACKGROUND: Different studies have shown that the use of olfactory stimuli during painful medical procedures reduces infants' response to pain. The main purpose of the current study was to investigate the effect of breast milk odor and vanilla odor on premature infants' vital signs including heart rate and blood oxygen saturation during and after venipuncture. METHODS: A total of 135 preterm infants were randomly selected and divided into three groups of control, vanilla odor, and breast milk odor. Infants in the breast milk group and the vanilla group were exposed to breast milk odor and vanilla odor from 5 minutes prior to sampling until 30 seconds after sampling. RESULTS: The results showed that breast milk odor has a significant effect on the changes of neonatal heart rate and blood oxygen saturation during and after venipuncture and decreased the variability of premature infants' heart rate and blood oxygen saturation. Vanilla odor has no significant effect on premature infants' heart rate and blood oxygen saturation. CONCLUSION: Breast milk odor can decrease the variability of premature infants' heart rate and blood oxygen saturation during and after venipuncture. PMID- 26560184 TI - Assessment of the Safety of Chondrocyte Sheet Implantation for Cartilage Regeneration. AB - We have previously studied the effects of chondrocyte sheets on the repair and regeneration of articular cartilage by using temperature-responsive culture inserts. On the basis of this work, we succeeded in rapid fabrication of chondrocyte sheets with the use of a coculture method in which inserts were placed between synoviocytes and chondrocytes. Treatment of cartilage defects using layered chondrocyte sheets promotes repair and regeneration; this method is compatible with in vivo osteoarthritis models that reproduce partial-thickness defects. In human stem cell clinical research guidelines, the Ministry of Health, Labour and Welfare (MHLW) approved several applications related to this technology. Indeed, its translation to a clinical setting is already yielding favorable results. In this study, we evaluated the risk of tumorigenesis associated with this treatment and characterized the dynamics of biological processes associated with the posttransplantation cell sheets in vivo. Furthermore, we also confirmed the safety of the procedure by using array comparative genomic hybridization (array CGH) and G-band staining to screen for deleterious genetic aberrations during prolonged subculture of cells. The safety of chondrocytes that were cultured for longer than normal was confirmed by the array CGH and G-band staining results. In addition, tumorigenicity testing confirmed that culture chondrocyte sheets are not tumorigenic. Furthermore, from the evaluation of bioluminescence imaging following implantation of the cell sheets, it was confirmed that the transplanted chondrocytes and synoviocytes remained in the knee joint and did not transfer elsewhere over time. We believe that the technique used in this study is a highly useful method for evaluating the safety of not only chondrocytes but also extensive subculturing in general. PMID- 26560185 TI - [Adequacy of therapeutic effort. A challenge on the way]. PMID- 26560186 TI - RGD mimetics gamma-AApeptides and methods of use (US 20,140,004,039 A1): a patent evaluation. AB - The patent (US 20140004039 A1) claims Arg-Gly-Asp (RGD) mimetics based on a new type of peptidomimetics - gamma-AApeptides - which display high binding affinity and specificity to integrin alphavbeta3. Integrin alphavbeta3 is one of the most important proteins involved in tumor angiogenesis and metastasis of solid tumors. It binds tightly to the tripeptide RGD, a prominent recognition motif found in extracellular matrix proteins. As alphavbeta3 is frequently upregulated during tumor angiogenesis, molecules mimicking the RGD recognition motif may target alphavbeta3 specifically and therefore can be used for cancer prevention or targeted diagnosis. Indeed, several positron emission tomography tracers targeting alphavbeta3 are currently under clinical investigation. gamma AApeptides as a new class of peptidomimetics show enhanced stability against proteolytic degradation and are amendable for derivatization due to their enormous chemodiversity. gamma-AApeptide-based RGD mimetics, including linear, cyclic and multimeric gamma-AApeptides, display comparable binding affinity and specificity to integrin alphavbeta3. These RGD mimetics can be synthesized easily on the solid phase and have been shown to be excellent positron emission tomography tracers by targeting glioblastoma tumor on the mouse model. As gamma AApeptide-based peptidomimetics are more stable than RGD peptides, they could be novel agents for the diagnostics and treatment of various cancers. PMID- 26560187 TI - Production of Human Albumin in Pigs Through CRISPR/Cas9-Mediated Knockin of Human cDNA into Swine Albumin Locus in the Zygotes. AB - Precise genome modification in large domesticated animals is desirable under many circumstances. In the past it is only possible through lengthy and burdensome cloning procedures. Here we attempted to achieve that goal through the use of the newest genome-modifying tool CRISPR/Cas9. We set out to knockin human albumin cDNA into pig Alb locus for the production of recombinant human serum albumin (rHSA). HSA is a widely used human blood product and is in high demand. We show that homologous recombination can occur highly efficiently in swine zygotes. All 16 piglets born from the manipulated zygotes carry the expected knockin allele and we demonstrated the presence of human albumin in the blood of these piglets. Furthermore, the knockin allele was successfully transmitted through germline. This success in precision genomic engineering is expected to spur exploration of pigs and other large domesticated animals to be used as bioreactors for the production of biomedical products or creation of livestock strains with more desirable traits. PMID- 26560188 TI - A 2015 focus on preventing drug-induced arrhythmias. AB - Drug-induced Torsade de Pointes arrhythmia is a life-threatening adverse effect feared by pharmaceutical companies. For the last decade, the cardiac safety guidelines have imposed human ether-a-go-go-related gene channel blockade and prolongation of QT interval as surrogates for proarrhythmic risk propensity of a new chemical entity. Suffering from a lack of specificity, this assessment strategy led to a great amount of false positive outcomes. Therefore, this review will discuss new pharmaceutical strategies: the cardiac safety proposal that recently emerged, the Comprehensive in vitro Proarrhythmia Assay, combining in vitro assays that integrate effects on main cardiac ion channels, with computational models of human ventricular action potential as well as assays using human stem cell-derived cardiomyocytes for an improved prediction of drug's proarrhythmic liability, alternative pharmacological perspectives as well as the current treatment of drug-induced long QT syndrome. PMID- 26560189 TI - i-TTM Model for Ab Initio-Based Ion-Water Interaction Potentials. 1. Halide-Water Potential Energy Functions. AB - New potential energy functions (i-TTM) describing the interactions between halide ions and water molecules are reported. The i-TTM potentials are derived from fits to electronic structure data and include an explicit treatment of two-body repulsion, electrostatics, and dispersion energy. Many-body effects are represented through classical polarization within an extended Thole-type model. By construction, the i-TTM potentials are compatible with the flexible and fully ab initio MB-pol potential, which has recently been shown to accurately predict the properties of water from the gas to the condensed phase. The accuracy of the i-TTM potentials is assessed through extensive comparisons with CCSD(T)-F12, DF MP2, and DFT data as well as with results obtained with common polarizable force fields for X(-)(H2O)n clusters with X(-) = F(-), Cl(-), Br(-), and I(-), and n = 1-8. By construction, the new i-TTM potentials will enable direct simulations of vibrational spectra of halide-water systems from clusters to bulk and interfaces. PMID- 26560190 TI - Depressive symptoms are associated with daytime sleepiness and subjective sleep quality in dementia with Lewy bodies. AB - OBJECTIVE: Sleep problems and depression are common symptoms in dementia with Lewy bodies (DLB), where patients typically experience subjectively poor sleep quality, fatigue and excessive daytime sleepiness. However, whilst sleep disturbances have been linked to depression, this relationship has not received much attention in DLB. The present cross-sectional study addresses this by examining whether depressive symptoms are specifically associated with subjective sleep quality and daytime sleepiness in DLB, and by examining other contributory factors. METHODS: DLB patients (n = 32) completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and the 15-item Geriatric Depression Scale (GDS-15). Motor and cognitive functioning was also assessed. Pearson correlations were used to assess the relationship between GDS-15, ESS and PSQI scores. RESULTS: GDS-15 scores were positively associated with both ESS (r = 0.51, p < 0.01) and PSQI (r = 0.59, p < 0.001) scores. CONCLUSIONS: Subjective poor sleep and daytime sleepiness were associated with depressive symptoms in DLB. Given the cross-sectional nature of the present study, the directionality of this relationship cannot be determined, although this association did not appear to be mediated by sleep quality or daytime sleepiness. Nevertheless, these findings have clinical relevance; daytime sleepiness or poor sleep quality might indicate depression in DLB, and subsequent work should examine whether the treatment of depression can reduce excessive daytime sleepiness and improve sleep quality in DLB patients. Alternatively, more rigorous screening for sleep problems in DLB might assist the treatment of depression. (c) 2015 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. PMID- 26560191 TI - Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium? AB - AIM: Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+ handling, left ventricular (LV) contractile response during Ca2+ administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48 h of RP. METHODS: Fifty three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+ administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+ uptake were measured. A graded treadmill test was performed in baseline and after RP (n = 14). In a separate group of animals (n = 5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions. RESULTS: Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+ . Post extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax ) of SR Ca2+ uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency. CONCLUSION: Forty-eight hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+ are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+ overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization. PMID- 26560192 TI - How to escape from Haller's rule: Olfactory system complexity in small and large Trichogramma evanescens parasitic wasps. AB - While Haller's rule states that small animals have relatively larger brains, minute Trichogramma evanescens Westwood (Hymenoptera: Trichogrammatidae) parasitic wasps scale brain size linearly with body size. This linear brain scaling allows them to decrease brain size beyond the predictions of Haller's rule, and is facilitated by phenotypic plasticity in brain size. In the present study we addressed whether this plasticity resulted in adaptations to the complexity of the morphology of the olfactory system of small and large T. evanescens. We used confocal laser scanning microscopy to compare size and number of glomeruli in the antennal lobe in the brain, and scanning electron microscopy to compare length and number of olfactory sensilla on the antennae. The results show a similar level of complexity of the olfactory system morphology of small and large wasps. Wasps with a similar genotype but very different brain and body size have similarly sized olfactory sensilla and most of them occur in equal numbers on the antennae. Small and large wasps also have a similar number of glomeruli in the antennal lobe. Glomeruli in small brains are, however, smaller in both absolute and relative volume. These similarities between small and large wasps may indicate that plasticity in brain size does not require plasticity in the gross morphology of the olfactory system. It may be vital for wasps of all sizes to have a large number of olfactory receptor types, to maintain olfactory precision in their search for suitable hosts, and consequently maintain their reproductive success and Darwinian fitness. PMID- 26560194 TI - Cancer Cell Radiobiological Studies Using In-House-Developed alpha-Particle Irradiator. AB - An alpha-particle irradiator, enabling high-precision irradiation of cells for in vitro studies, has been constructed. The irradiation source was a (241)Am source, on which well inserts containing cancer cells growing in monolayer were placed. The total radioactivity, uniformity, and alpha-particle spectrum were determined by use of HPGe detector, Gafchromic dosimetry film, and PIPS detector measurements, respectively. Monte Carlo simulations were used for dosimetry. Three prostate cancer (LNCaP, DU145, PC3) and three pancreatic cancer (Capan-1, Panc-1, BxPC-3) cell lines were irradiated by alpha-particles to the absorbed doses 0, 0.5, 1, and 2 Gy. For reference, cells were irradiated using (137)Cs to the absorbed doses 0, 1, 2, 4, 6, 8, and 10 Gy. Radiation sensitivity was estimated using a tetrazolium salt-based colorimetric assay with absorbance measurements at 450 nm. The relative biological effectiveness for alpha-particles relative to gamma-irradiation at 37% cell survival for the LNCaP, DU145, PC3, Capan-1, Panc-1, and BxPC-3 cells was 7.9 +/- 1.7, 8.0 +/- 0.8, 7.0 +/- 1.1, 12.5 +/- 1.6, 9.4 +/- 0.9, and 6.2 +/- 0.7, respectively. The results show the feasibility of constructing a desktop alpha-particle irradiator as well as indicate that both prostate and pancreatic cancers are good candidates for further studies of alpha-particle radioimmunotherapy. PMID- 26560193 TI - Strengths and Weaknesses of a Planar Whole-Body Method of (153)Sm Dosimetry for Patients with Metastatic Osteosarcoma and Comparison with Three-Dimensional Dosimetry. AB - PURPOSE: Dosimetric accuracy depends directly upon the accuracy of the activity measurements in tumors and organs. The authors present the methods and results of a retrospective tumor dosimetry analysis in 14 patients with a total of 28 tumors treated with high activities of (153)Sm-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) for therapy of metastatic osteosarcoma using planar images and compare the results with three-dimensional dosimetry. MATERIALS AND METHODS: Analysis of phantom data provided a complete set of parameters for dosimetric calculations, including buildup factor, attenuation coefficient, and camera dead time compensation. The latter was obtained using a previously developed methodology that accounts for the relative motion of the camera and patient during whole-body (WB) imaging. Tumor activity values calculated from the anterior and posterior views of WB planar images of patients treated with (153)Sm EDTMP for pediatric osteosarcoma were compared with the geometric mean value. The mean activities were integrated over time and tumor-absorbed doses were calculated using the software package OLINDA/EXM. RESULTS: The authors found that it was necessary to employ the dead-time correction algorithm to prevent measured tumor activity half-lives from often exceeding the physical decay half-life of (153)Sm. Measured half-lives so long are unquestionably in error. Tumor-absorbed doses varied between 0.0022 and 0.27 cGy/MBq with an average of 0.065 cGy/MBq; however, a comparison with absorbed dose values derived from a three-dimensional analysis for the same tumors showed no correlation; moreover, the ratio of three dimensional absorbed dose value to planar absorbed dose value was 2.19. From the anterior and posterior activity comparisons, the order of clinical uncertainty for activity and dose calculations from WB planar images, with the present methodology, is hypothesized to be about 70%. CONCLUSION: The dosimetric results from clinical patient data indicate that absolute planar dosimetry is unreliable and dosimetry using three-dimensional imaging is preferable, particularly for tumors, except perhaps for the most sophisticated planar methods. The relative activity and patient kinetics derived from planar imaging show a greater level of reliability than the dosimetry. PMID- 26560195 TI - Synthesis, Radiolabeling, and Bioevaluation of Bis(Trifluoromethanesulfonyl) Imide. AB - Imidazolium salts have antitumor potential and toxicological effects on various microorganisms. The authors' aim is to synthesize a new imidazolium salt and to assess its pharmacokinetic and antitumor potentials by in vitro and in vivo studies. In this study, bis(trifluoromethanesulfonyl) imide (ITFSI) was synthesized and labeled with (131)I using the iodogen method. The efficiency of radiolabeling was determined with high yield (95.5% +/- 3.7%). Pharmacokinetic properties of the compound were investigated in albino Wistar rats using radiolabeled compound. The radiolabeled compound ((131)I-ITFSI) has been stable during a period of 3 hours in human serum. The uptake of (131)I-ITFSI reached maximum in the spleen, liver, and blood at 60 minutes, large intestine and heart at 30 minutes, and ovary at 120 minutes. It is observed that intracellular uptake of the radiolabeled compound is higher in the CaCo-2 (colon adenocarcinoma tumor) cell line than HEK-293 (human epithelial kidney) cell line. In further study, antitumor potential of ITFSI on a colon adenocarcinoma tumor-bearing animal model may be investigated. PMID- 26560196 TI - Claudin 8 Contributes to Malignant Proliferation in Human Osteosarcoma U2OS Cells. AB - Human osteosarcoma (OS) represents one of the most common primary sarcomas often originating in the metaphyses of long bones. However, its underlying molecular pathogenesis is still only vaguely understood. Several tight junction proteins were shown to be associated with and involved in tumorigenesis. This study is aimed to evaluate the role of Claudin 8 (CLDN8) in human OS. Lentivirus-based short hairpin RNA targeting CLDN8 specifically depleted its endogenous expression in U2OS and SW1353 OS cells, with a reduction by 97.7% and 89.3%, respectively, in contrast to control. Depletion of CLDN8 led to a significant diminution in cell viability and proliferation. To test the mechanism by which CLDN8 modulates cell proliferation, the flow cytometry assay and apoptosis assay were performed and confirmed that G1-S transition was blocked and a strong proapoptotic effect was induced in U2OS cells by CLDN8 knockdown. These data demonstrate that CLDN8 plays an essential role in OS proliferation in vitro, which will provide a new opportunity for discovering and identifying novel effective treatment strategies. PMID- 26560197 TI - Methods of preservation and flotation for the detection of nematode eggs and coccidian oocysts in faeces of the forest musk deer. AB - Parasitic infections influence the health of captive forest musk deer (Moschus berezovskii) and affect population increases. Nevertheless, there are few quantitative studies regarding forest musk deer parasites, and there is no common preservation method or flotation solution used for detection of faecal parasites because of the biology of the worms and the host physiological state. The objective of this study was to evaluate preservation and flotation methods for the detection of nematode eggs and coccidian oocysts in faeces of the forest musk deer. The McMaster technique was used to count nematode eggs and coccidian oocysts in 33 samples of faeces. For the nematode eggs, the differences among flotation solutions were significant (P< 0.01), with sodium nitrate being the best flotation solution, and the combination of freezing and sodium nitrate resulted in the greatest number of eggs per gram (EPG = 209.4 +/- 67.8). For the coccidian oocysts, the interaction between preservation method and flotation solution was significant (P< 0.01), and the combination of formalin and sodium chloride yielded the greatest number of oocysts per gram (OPG = 1010.7 +/- 162.3). The forest musk deer had a high prevalence of parasitic infections, with the parasite load of coccidia (96.4%) significantly greater than that of nematodes (71.9%, P< 0.01). These results confirm that captive forest musk deer suffer from serious parasitic invasions and demonstrate that the novel method described here could be utilized for parasitological diagnosis, detection and prevention in species of Moschidae and Cervidae. PMID- 26560198 TI - Early dysautonomia detected by heart rate variability predicts late depression in female patients following mild traumatic brain injury. AB - Depression is one of the frequent complications following a mild traumatic brain injury (mTBI). Recent research indicated that abnormalities in the autonomic nervous system (ANS) can be evaluated by a noninvasive power spectral analysis of the heart rate variability (HRV). In this study, we investigated whether a frequency-domain analysis of HRV was correlated with late depression in mTBI patients. In total, 181 patients diagnosed with mTBI and 83 volunteers as healthy controls were recruited in 2010-2014. Beck Depression Inventory (BDI) scores were used to evaluate depression in the 1st week of assessment and at 1.5-, 3-, 6-, 12 , and 18-month follow-ups. Correlation and logistic regression analyses of the 1st week HRV parameters with BDI scores at 18 months were performed in individual female mTBI patients. Female mTBI patients were more vulnerable to depression accompanied by reduced HRV compared to healthy controls. Over time, depression was aggravated in female mTBI patients but was alleviated in male mTBI patients. A significantly lower parasympathetic proportion of the ANS was noted at 18 months with respect to the 1st week in female mTBI patients. In addition, depression in female mTBI patients at 18 months after injury was significantly correlated with a decrease in the parasympathetic proportion of the ANS in the 1st week (rho = -0.411; p < .05). Dysautonomia resulted in higher risks of depression in female mTBI patients. We concluded that early dysautonomia following an mTBI contributes to late depression in female mTBI patients. PMID- 26560199 TI - A laboratory exercise to illustrate protein-membrane interactions. AB - The laboratory protocol presented here takes about 3 hours to perform and investigates protein and lipid interactions. Students first purify His6 -tagged human apolipoprotein A-I (apoA-I) with Ni-NTA affinity resin in a simple batch protocol and prepare multilamellar vesicles (MLV) from pre-dried phospholipid films. When apoA-I is added to the MLV, much smaller protein/lipid nanodisc complexes are formed in some instances. Nanodisc formation can be monitored by a decrease in light-scattering intensity at 340 nm using a simple spectrophotometer. Students will observe nanodisc formation with MLV formed from the anionic phospholipid dimyristoylphosphatidyl glycerol, which pack poorly into lipid bilayers, but not with MLV formed from the zwitterionic phospholipid dimyristoyl phosphatidylcholine, which form stable bilayers. This laboratory exercise is accompanied by questions and exercises that enable students a deeper of the dimensions of apoA-I and nanodiscs as well as the biological relevance of nanodisc formation in the process of reverse cholesterol transport. PMID- 26560200 TI - Management of Orbital and Periocular Vascular Anomalies. AB - PURPOSE: To review the treatment modalities available to clinicians who treat orbital and periocular vascular anomalies, with a focus on newer approaches. METHODS: The authors' experience, along with a literature review, was used to provide a concise summary of the available approaches to the treatment of periocular vascular anomalies. Emerging diagnostic tools and therapies are highlighted. RESULTS: The treatment of orbital and periocular vascular anomalies, including vascular malformations and tumors, increasingly utilizes a multidisciplinary team and a combination of endovascular, percutaneous, and open surgical techniques. CONCLUSIONS: A growing reliance on new instrumentation and tools in a team-oriented approach to treatment may lead to better results with improved visual function and cosmesis and with reduced risk of complications. PMID- 26560201 TI - Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. AB - Different genetic variations in the catechol-O-methyltransferase (COMT) gene have been indicated to functionally regulate the encoded enzyme. Despite the vast literature on the single nucleotide COMT ValMet polymorphism, the impact of complex haplotypes on cognitive functions has been overlooked. Here we contrasted the effects of complex COMT haplotypes with the ValMet polymorphism on cognitive functions and their interaction with menopause, in healthy subjects and patients with schizophrenia. Healthy adults (N=229) as well as patients with schizophrenia (N=172) underwent a comprehensive cognitive assessment taking into account the menopausal state. Functional COMT variations selectively modulated working memory and executive functions. Strikingly, these effects were present only in adult men but not in women before menopause, in both healthy subjects and patients with schizophrenia. Importantly, the same pattern of COMT-dependent effects present in men reappeared in women after menopause. Thus, functional COMT mutations seem to modulate cognitive functions depending on the hormonal status. These data clarify the importance of taking into account the combined effect of sex, hormonal status and genetics. PMID- 26560202 TI - Surface hydrogenation regulated wrinkling and torque capability of hydrogenated graphene annulus under circular shearing. AB - Wrinkles as intrinsic topological feature have been expected to affect the electrical and mechanical properties of atomically thin graphene. Molecular dynamics simulations are adopted to investigate the wrinkling characteristics in hydrogenated graphene annulus under circular shearing at the inner edge. The amplitude of wrinkles induced by in-plane rotation around the inner edge is sensitive to hydrogenation, and increases quadratically with hydrogen coverage. The effect of hydrogenation on mechanical properties is investigated by calculating the torque capability of annular graphene with varying hydrogen coverage and inner radius. Hydrogenation-enhanced wrinkles cause the aggregation of carbon atoms towards the inner edge and contribute to the critical torque strength of annulus. Based on detailed stress distribution contours, a shear-to tension conversion mechanism is proposed for the contribution of wrinkles on torque capacity. As a result, the graphane annulus anomalously has similar torque capacity to pristine graphene annulus. The competition between hydrogenation caused bond strength deterioration and wrinkling induced local stress state conversion leads to a U-shaped evolution of torque strength relative to the increase of hydrogen coverage from 0 to 100%. Such hydrogenation tailored topological and mechanical characteristics provides an innovative mean to develop novel graphene-based devices. PMID- 26560203 TI - Room Temperature Electrical Detection of Spin Polarized Currents in Topological Insulators. AB - Topological insulators (TIs) are a new class of quantum materials that exhibit a current-induced spin polarization due to spin-momentum locking of massless Dirac Fermions in their surface states. This helical spin polarization in three dimensional (3D) TIs has been observed using photoemission spectroscopy up to room temperatures. Recently, spin polarized surface currents in 3D TIs were detected electrically by potentiometric measurements using ferromagnetic detector contacts. However, these electric measurements are so far limited to cryogenic temperatures. Here we report the room temperature electrical detection of the spin polarization on the surface of Bi2Se3 by employing spin sensitive ferromagnetic tunnel contacts. The current-induced spin polarization on the Bi2Se3 surface is probed by measuring the magnetoresistance while switching the magnetization direction of the ferromagnetic detector. A spin resistance of up to 70 mOmega is measured at room temperature, which increases linearly with current bias, reverses sign with current direction, and decreases with higher TI thickness. The magnitude of the spin signal, its sign, and control experiments, using different measurement geometries and interface conditions, rule out other known physical effects. These findings provide further information about the electrical detection of current-induced spin polarizations in 3D TIs at ambient temperatures and could lead to innovative spin-based technologies. PMID- 26560204 TI - Novel features of the ISC machinery revealed by characterization of Escherichia coli mutants that survive without iron-sulfur clusters. AB - Biological assembly of iron-sulfur (Fe-S) clusters is mediated by complex systems consisting of multiple proteins. Escherichia coli possesses two distinct systems called the ISC and SUF machineries encoded by iscSUA-hscBA-fdx-iscX and sufABCDSE respectively. Deletion of both pathways results in absence of the biosynthetic apparatus for Fe-S clusters, and consequent lethality, which has hampered detailed genetic studies. Here we report that modification of the isoprenoid biosynthetic pathway can offset the indispensability of the Fe-S cluster biosynthetic systems and show that the resulting Deltaisc Deltasuf double mutants can grow without detectable Fe-S cluster-containing proteins. We also constructed a series of mutants in which each isc gene was disrupted in the deletion background of sufABCDSE. Phenotypic analysis of the mutants revealed that Fdx, an essential electron-transfer Fe-S protein in the ISC machinery, is dispensable under anaerobic conditions, which is similar to the situation with IscA. Furthermore, we found that several suppressor mutations in IscU, an Fe-S scaffold protein responsible for the de novo Fe-S cluster assembly, could bypass the essential role of the chaperone system HscA and HscB. These findings pave the way toward a detailed molecular analysis to understand the mechanisms involved in Fe S cluster biosynthesis. PMID- 26560206 TI - Quality of life, self-esteem and psychosocial factors in adolescents with acne vulgaris. AB - BACKGROUND: Dermatological diseases, among which acne vulgaris, have psychological impact on the affected generating feelings of guilt, shame and social isolation. OBJECTIVES: To compare quality of life, self-esteem and other psychosocial variables amongst adolescents with and without acne vulgaris, and between levels of severity. METHODS: Cross-sectional observational study in a sample of 355 high school students from the city of Joao Pessoa. Data collection was performed with questionnaires and clinical-dermatological evaluation. The primary variables were the incidence of AV; quality of life, set by the Children's Dermatology Quality of Life Index and Dermatology Quality of Life Index; and self-esteem, measured by the Rosenberg Self-Esteem Scale. For calculation of statistical tests, we used the SPSS 20.0 software, considering p=0.05. RESULTS: The sample, with an average age of 16, showed 89.3% prevalence of acne vulgaris. The most prevalent psychosocial issue was "afraid that acne will never cease", present in 58% of affected youth. The median score of Quality of Life in Children's Dermatology Index was different amongst students with and without acne vulgaris (p=0.003), as well as the Quality of Life in Dermatology (p=0.038) scores, so that students with acne vulgaris have worse QoL. There was a correlation between the severity of acne vulgaris and worse quality of life. Self esteem was not significantly associated with the occurrence or severity of acne vulgaris. CONCLUSIONS: acne vulgaris assumes significance in view of its high prevalence and the effect on quality of life of adolescents, more severe at the more pronounced stages of disease (p<0.001). The psychosocial impact of acne vulgaris should be valued in the management of patients with this condition. PMID- 26560205 TI - Coccidioidomycosis and the skin: a comprehensive review. AB - Coccidioidomycosis is a highly prevalent disease in the Western hemisphere. It is considered one of the most virulent primary fungal infections. Coccidioides species live in arid and semi-arid regions, causing mainly pulmonary infection through inhalation of arthroconidia although many other organs can be affected. Primary inoculation is rare. Since the first case of coccidioidomycosis was reported in 1892, the skin has been identified as an important target of this disease. Knowledge of cutaneous clinical forms of this infection is important and very useful for establishing prompt diagnosis and treatment. The purpose of this article is to provide a review of this infection, emphasizing its cutaneous manifestations, diagnostic methods and current treatment. PMID- 26560207 TI - Dermatology relevance to graduates from the Universidade Estadual de Campinas Medical School. AB - BACKGROUND: Some research indicates that physicians do not dominate the expected dermatological content for the proper exercise of the profession. This fact compromises their diagnostic and therapeutic performance, generating unnecessary costs. OBJECTIVE: The aim of this study was to evaluate the relevance of Dermatology and the knowledge acquired in the specialty during the undergraduate course in clinical practice of graduates at the State University of Campinas Medical School (FCM/UNICAMP). METHOD: A questionnaire with 22 closed questions and two open ones was electronically sent to physicians who had graduated more than 10 years ago and others for less than 10 years. In the first group, physicians were trained by the same curriculum and in the second group there were subjects trained by the old and the new curriculum. RESULTS: Of the 126 respondents, 83% had completed a specialization course. Among all, 82% did not study dermatology after graduation. The majority considered that Dermatology has high relevance in clinical practice, regardless of the group. There was a statistically significant difference between non-dermatologist doctors graduated for more than 10 years and those graduated for less than 10 years regarding confidence about lesion diagnosis, diagnostic investigation and treatment of skin diseases. Physicians who have graduated for a longer time feel more insecure in relation to patients with dermatoses. Concerning contributions offered by graduation program completion they prioritized outpatient care, ability to diagnose, knowledge of pathology, research and knowledge of lesions. CONCLUSION: This study has shown that Dermatology is relevant in medical practice and more recent graduates from the FCM/UNICAMP feel less insecure when treating a patient with dermatoses. PMID- 26560208 TI - Study of the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011. AB - BACKGROUND: Cutaneous melanoma (CM) is considered serious for causing frequent metastasis, presenting high mortality, resistance to available therapies and incidences in laboring activity. OBJECTIVES: To study the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011, according to risk factors, location of lesions, Clark levels and Breslow thickness. METHODS: A descriptive, retrospective and quantitative research in reports of the Servicos de Anatomia Patologica in Palmas (SAPP) and Registro de Cancer de Base Populacional de Palmas (RCBPP). RESULTS: The years of highest incidences were: 2004 (8 cases/17.8%), 2008 and 2011 (7 cases each/15.6%) and 2010 (6 cases/13.3%). Among the 45 cases studied, there were predominance in patients between 41 and 60 years old, women, caucasians, farmers, located in trunk, in situ type, superficial extensive and metastatic cutaneous, Clark levels I (20%) and IV (17.7%), Breslow thickness <=1 mm (35.5%) and 2.01 to 4 mm (24.4%). CONCLUSIONS: The most common histopathological types were: cutaneous melanoma in situ, superficial extensive and metastatic, followed by nodular cutaneous melanoma, and finally, by other forms. In this study, Clark levels and Breslow thickness pointed to greater importance of thin melanomas and sun exposure without appropriate protection in farmers. PMID- 26560209 TI - Factors influencing citations to systematic reviews in skin diseases: a cross sectional study through Web of Sciences and Scopus. AB - BACKGROUND: Disseminating information derived from systematic reviews is a fundamental step for translating evidence into practice. OBJECTIVE: To determine which features of dermatological SR are associated with systematic review dissemination, using citation rates as an indicator. METHODS: Dermatological systematic reviews published between 2008 and 2012 were obtained from Scopus, the ISI Web of Sciences and the Cochrane Skin Group. Bibliometric data of every systematic review were collected and analyzed. RESULTS: A total of 320 systematic reviews were analyzed. Univariable analysis showed that the journal impact factor, number of authors, and total references cited were positively associated with the number of citations. There was a significant difference in the median number of citations with regard to the corresponding author's country, type of skin disease, type of funding, and presence of international collaboration. Cochrane reviews were significantly associated with a lower number of citations. Multivariable analysis found that the number of authors, number of references cited and the corresponding author from United Kingdom were independently correlated with many citations. Cochrane systematic reviews tended to be independently associated with a lower number of citations. CONCLUSIONS: Citation number to systematic reviews may be improving by increasing the number of authors, especially collaborative authors, and the number of cited references. The reasons for the association of Cochrane SRs with fewer citations should be addressed in future studies. PMID- 26560210 TI - Leprosy in a University Hospital in Southern Brazil. AB - BACKGROUND: Leprosy is an infectious disease that may lead to irreversible nerve damage, compromising patient's quality of life and leading to loss of working years. OBJECTIVES: To evaluate the epidemiological profile of patients followed at a University Hospital. MATERIALS AND METHODS: This is a retrospective observational study, based on a review of medical records. We studied the clinical and epidemiological features of patients with leprosy monitored at the Hospital de Clinicas of the Federal University of Parana between January 2005 and January 2010. RESULTS: The mean age was 47.51, while 35.94% of patients were aged 41-60. The male:female rate was 1.8:1. The most prevalent occupations were: retired, students or rural workers. Patients came mainly from Curitiba or nearby areas, but there were also patients from the countryside. The mean diagnostic delay was 24.57 months. Multibacillary forms prevailed, with the lepromatous variety being the most common, closely followed by the borderline type. Neural enlargement was found in more than 50% of the patients and 48.44% of them developed reactional states. Hemolysis was the most commonly detected drug side effect. Initial functional evaluation was possible in 70% of patients, 55% of whom had disabilities upon diagnosis. The most prevalent associated disease was hypertension. CONCLUSIONS: This study showed an important diagnostic delay and a high rate of sequelae in this specific population. Brazil is one of the few remaining countries that has not yet eradicated leprosy and it is important to improve health policies in order to prevent sequelae and achieve eradication. PMID- 26560212 TI - Lichen planopilaris epidemiology: a retrospective study of 80 cases. AB - BACKGROUND: Lichen planopilaris is a frequent presentation of primary cicatricial alopecia. Scalp distribution characterizes the main clinical presentations: classic lichen planopilaris, frontal fibrosing alopecia and Graham-Little Piccardi-Lassueur Syndrome (GLPLS). OBJECTIVE: Description of the clinical, dermoscopic and histopathological findings of Lichen planopilaris in public and private practices. METHOD: A retrospective observational study was performed by reviewing medical records of patients with lichen planopilaris. RESULTS: Eighty patients were included, 73 (91,25%) were female. Prototype II was seen in 53 (66,25%) patients. Classic lichen planopilaris was seen in 62,5% of the cases. Frontal fibrosing alopecia was seen in 31% of the patients and only one patient presented Graham-Little Piccardi-Lassueur Syndrome (GLPLS). Scalp lesions were scattered throughout the scalp in 47 (58,75%) of the patients, while 24 (30%) presented mainly central scalp lesions, 29 (36,25%) presented marginal lesions and only 4 (5%) patents had vertex lesions. CONCLUSIONS: Clinical presentation of Lichen planopilaris varies. To recognize the heterogeneity of the clinical appearance in lichen planopilaris is important for differential diagnosis. PMID- 26560211 TI - Research of primary hyperhidrosis in students of medicine of the State of Sergipe, Brazil. AB - BACKGROUND: Hyperhidrosis or excessive sweat production occurs at 2.9-9% of the population. OBJECTIVE: To estimate the prevalence and disorders due to primary hyperhidrosis (HP) in medicine students in the state of Sergipe. METHODS: Cross sectional study using individual interviews. RESULTS: Hyperhidrosis was found in 14.76% of subjects, the most affected regions were palmar, plantar and axillary, causing prejudice in daily activities. Family history occurred in 45% and 22.72% was diagnosed by a physician. CONCLUSION: The prevalence of hyperhidrosis in medicine students of Sergipe was high, with strong family and a small portion of diagnoses made by medical professionals. PMID- 26560213 TI - Patch test results in children and adolescents. Study from the Santa Casa de Belo Horizonte Dermatology Clinic, Brazil, from 2003 to 2010. AB - BACKGROUND: Patch testing is an efficient method to identify the allergen responsible for allergic contact dermatitis. OBJECTIVE: To evaluate the results of patch tests in children and adolescents comparing these two age groups' results. METHODS: Cross-sectional study to assess patch test results of 125 children and adolescents aged 1-19 years, with suspected allergic contact dermatitis, in a dermatology clinic in Brazil. Two Brazilian standardized series were used. RESULTS: Seventy four (59.2%) patients had "at least one positive reaction" to the patch test. Among these positive tests, 77.0% were deemed relevant. The most frequent allergens were nickel (36.8%), thimerosal (18.4%), tosylamide formaldehyde resin (6.8%), neomycin (6.4%), cobalt (4.0%) and fragrance mix I (4.0%). The most frequent positive tests came from adolescents (p=0.0014) and females (p=0.0002). There was no relevant statistical difference concerning contact sensitizations among patients with or without atopic history. However, there were significant differences regarding sensitization to nickel (p=0.029) and thimerosal (p=0.042) between the two age groups under study, while adolescents were the most affected. CONCLUSION: Nickel and fragrances were the only positive (and relevant) allergens in children. Nickel and tosylamide formaldehyde resin were the most frequent and relevant allergens among adolescents. PMID- 26560214 TI - Hieronymi Fracastorii: the Italian scientist who described the "French disease". AB - Girolamo Fracastoro was a true Italian Renaissance man: he excelled in literature, poetry, music, geography, geology, philosophy, astronomy and, of course, medicine to the point that made Charles-Edward Armory Winslow define him as "a peak unequaled by anyone between Hippocrates and Pasteur". In 1521 Fracastoro wrote the poem "Syphilis Sive de Morbo Gallico" in which was established the use of the term "syphilis" for this terrible and inexplicably transmitted disease, often referred to as "French disease" by the people of the time and by Fracastoro himself. PMID- 26560217 TI - Dermal type I collagen assessment by digital image analysis. AB - Type I collagen is the main dermal component, and its evaluation is relevant to quantitative studies in dermatopathology. However, visual gradation (0 to 4+) has low precision and high subjectivity levels. This study aimed to develop and validate a digital morphometric analysis technique to estimate type I collagen levels in the papillary dermis. Four evaluators visually quantified (0 to 4+) the density of type I collagen in 63 images of forearm skin biopsies marked by immunohistochemistry and two evaluators analyzed the same images using digital morphometric techniques (RGB split colors (I) and color deconvolution (II)). Automated type I collagen density estimation in the papillary dermis (two techniques) were correlated with visual evaluations (Spearman's rho coefficients of 0.48 and 0.62 (p<0.01)). With regard to the inter-observer repeatability, the four evaluators who used visual classification had an intraclass correlation coefficient (for absolute agreement) of 0.53, while the other two evaluators who used digital analysis (algorithm II) had an intraclass correlation coefficient of 0.97. PMID- 26560216 TI - Radiofrequency for the treatment of skin laxity: mith or truth. AB - The nonablative radiofrequency is a procedure commonly used for the treatment of skin laxity from an increase in tissue temperature. The goal is to induce thermal damage to thus stimulate neocollagenesis in deep layers of the skin and subcutaneous tissue. However, many of these devices haven't been tested and their parameters are still not accepted by the scientific community. Because of this, it is necessary to review the literature regarding the physiological effects and parameters for application of radiofrequency and methodological quality and level of evidence of studies. A literature search was performed in MEDLINE, PEDro, SciELO, PubMed, LILACS and CAPES and experimental studies in humans, which used radiofrequency devices as treatment for facial or body laxity, were selected. The results showed that the main physiological effect is to stimulate collagen synthesis. There was no homogeneity between studies in relation to most of the parameters used and the methodological quality of studies and level of evidence for using radiofrequency are low. This fact complicates the determination of effective parameters for clinical use of this device in the treatment of skin laxity. The analyzed studies suggest that radiofrequency is effective, however the physiological mechanisms and the required parameters are not clear in the literature. PMID- 26560218 TI - Persistent docetaxel-induced supravenous erythematous eruption. AB - Taxanes are drugs used to treat many types of cancer, including breast and lung cancer. The most common side effects of these drugs are neutropenia and mucositis. Signs of skin toxicity are observed in about 65% of cases and include alopecia, hypersensitivity reactions, persistent supravenous erythematous eruption, nail changes, scleroderma reactions and others. We report two cases of skin reaction to docetaxel and warn that it is not necessary to interrupt the treatment in these cases. PMID- 26560215 TI - Cutaneous primary B-cell lymphomas: from diagnosis to treatment. AB - Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies. PMID- 26560219 TI - First case of congenital idiopathic hypohidrosis in China. AB - A 43-year-old Chinese man presented with generalized hypohidrosis, which he had had since birth, without obvious abnormalities of other skin appendages except a sparse beard and axillary hairs. The sweat test revealed localized sweating on the face, axillae and palms. Histopathologic examination showed that the sweat glands were absent in the forearm and thigh, but some eccrine and apocrine sweat glands were present in the right axilla. S-100 was expressed in the nerve terminals surrounding the acini and ducts of the eccrine sweat glands, while PGP9.5 was positive in the acini of apocrine glands and the nerve terminals surrounding the eccrine glands in the axilla. To our knowledge, this is the first case of congenital idiopathic hypohidrosis in China. PMID- 26560220 TI - Granuloma faciale: a good therapeutic response with the use of topical tacrolimus. AB - Granuloma faciale is a rare dermatosis of chronic course, benign, usually asymptomatic, first described in 1945 by Wingley. It is characterized by the appearance of well-defined, single or multiple papules, plaques and nodules, predominantly located in sun-exposed areas, especially the face. In this work we report the case of a female patient, 58 years old, evolving for ten years with multiple erythematous-brownish and asymptomatic papules on the face, whose histological examination confirmed the diagnosis of granuloma faciale. The patient was treated with topical tacrolimus, evolving with regression of lesions. PMID- 26560221 TI - Hypopigmented macules of the limbs in two sisters: report on familial Bier spots. AB - Bier spots are asymptomatic, small, irregular, hypopigmented macules characterized by a normal histological appearance, which are usually found on the arms and legs of young adults. We describe the simultaneous presence of Bier spots in two siblings. This finding is unusual since, to the best of our knowledge, concurrent familial cases have never been reported in the literature. PMID- 26560222 TI - Mycobacterium abscessus skin infection after tattooing--Case report. AB - Mycobacterium abscessus is a rapidly growing mycobacterium that has been affecting people undergoing invasive procedures, such as videosurgery and mesotherapy. This bacterium has global distribution, being found in numerous niches. The frequency of published reports of infection by rapidly growing mycobacteria associated with tattooing procedures has increased in recent years. However, in Brazil there were no case reports of M. abscessus after tattooing in the literature until now. In this paper, we describe the case of a patient with a nine-month history of lesion on a tattoo site. The diagnosis of infection with Mycobacterium abscessus was established by correlation between dermatological and histopathological aspects, culture and molecular biology techniques. The patient had significant improvement of symptoms with the use of clarithromycin monotherapy. PMID- 26560223 TI - Amantadine-induced livedo reticularis--Case report. AB - Livedo reticularis is a spastic-anatomical condition of the small vessels which translates morphologically by a reticular pattern, interspersing cyanosis, pallor and erythema. The same can be congenital or acquired. Among the acquired, we highlight the physiological livedo reticularis and the idiopathic livedo by vasospasm; the latter configures the most common cause. The drug-induced type is less common. The drugs amantadine and norepinephrine are often implicated. Cyanosis is usually reversible if the causative factor is removed, however, with chronicity, the vessels may become permanently dilated and telangiectatic. We report a case of a patient diagnosed with Parkinson's disease with chronic livedo reticularis associated with the use of amantadine and improvement after discontinuation of the drug. PMID- 26560224 TI - Mucosal-dominant pemphigus vulgaris in a captopril-taking woman with angioedema. AB - We describe a 39-year-old woman with an apparent captopril-induced, contact mucosal-dominant pemphigus vulgaris and angioedema, who took captopril during a bout of arterial hypertension. This exposure suggests that captopril and pathophysiology of angioedema stimulated the development of pemphigus vulgaris, which was diagnosed using the novel, indirect immunofluorescence BIOCHIP mosaic, with the modification to detect serum IgG4 autoantibodies. We discuss the patient, who experienced a chain of events leading to the active stage of pemphigus vulgaris, and review concepts of pemphigus vulgaris inducible by drugs and pathological immunity. PMID- 26560225 TI - Scanning electron microscopy of superficial white onychomycosis. AB - Superficial white onychomycosis is characterized by opaque, friable, whitish superficial spots on the nail plate. We examined an affected halux nail of a 20 year-old male patient with scanning electron microscopy. The mycological examination isolated Trichophyton mentagrophytes. Abundant hyphae with the formation of arthrospores were found on the nail's surface, forming small fungal colonies. These findings showed the great capacity for dissemination of this form of onychomycosis. PMID- 26560226 TI - Histoid leprosy: a rare exuberant case. AB - Leprosy is a neglected disease. We point up the need of recognizing the unusual clinical presentations of the disease in order to make early diagnosis and proper treatment possible, and break the transmission chain. The authors report a rare type of multibacillary leprosy: histoid leprosy and present images of numerous well-circumscribed indurated papules and nodules distributed throughout the entire body. PMID- 26560227 TI - Syndrome in question. AB - Muir-Torre syndrome is a rare genodermatosis characterized by the occurrence of at least one sebaceous tumor associated with visceral neoplasia, but with no predisposing factors. The sebaceous neoplasm may appear before, during or after the diagnosis of colorectal cancer. As it is regarded as a subtype of nonpolyposis hereditary colorectal cancer, it is important to evaluate the patient's first-degree relatives. The clinical course of the neoplasm is usually more indolent and the syndrome has a good prognosis. We report the case of a patient who, after a ten-year diagnosis of colorectal cancer, presented with multiple sebaceous neoplasms. PMID- 26560228 TI - Prevalence of dermatoses in dermatologic evaluation requests from patients admitted to a tertiary hospital for 10 years. AB - Skin diseases are common in hospitalized patients. However, there is a lack of data concerning their frequency. The objective of this study is to evaluate the prevalence of dermatological diagnoses in hospitalized patients after consultation requested by non-dermatologist physicians to the Department of Dermatology, Hospital de Clinicas de Porto Alegre period of 10 years. A total of 5685 patients were evaluated, representing an average of 48.2 patients per month. The five most frequent groups were infectious dermatoses(33.25%), eczematous dermatoses (11.49%), drug reactions (11.43%), vascular dermatoses (6.81%) and group of pruritus, prurigo nodularis and urticaria (hives) (4.71%). PMID- 26560229 TI - Do steroid hormones have an important role on cutaneous lupus physiopathology? PMID- 26560230 TI - Bier spots and unilateral nevoid telangiectasia: more than just a coincidence. PMID- 26560231 TI - Erratum. AB - A mistake was made in article Bottino CB, Guimaraes TF, Gomes FR, D'Acri AM, Lima RB, Martins CJ. Solitary eccrine syringofi broadenoma: a case report. An Bras Dermatol. 2015;90(3 Suppl 1):S235-8. Image 2 was switched for image 3 and vice versa. Figure 2 should show the image of a skin lesion (ankle nodule) and Figure 3 should show the image of the histopathological exam. The legends are correct. Follows the corrected imags. PMID- 26560232 TI - Enhanced Ionic Conductivity and Power Generation Using Ion-Exchange Resin Beads in a Reverse-Electrodialysis Stack. AB - Reverse electrodialysis (RED) is a promising technique for harvesting energy by mixing seawater with river water. The energy production is usually limited by ionic conductivity in dilute compartments of a RED system. Novel tests were conducted in this research, which used ion-exchange resin beads (IERB) to replace nonconductive spacer fabrics in RED compartments with dilute NaCl solution in a modified stack containing Fumasep FKS and Fumasep FAS membranes. We compared the conductivity of an IERB packed bed with that of an inert glass-beads-packed bed as a control to confirm IERB's effectiveness. When applied in a RED system, IERB decreased the stack resistance by up to 40%. The maximum gross power density improved by 83% in the RED stack compared to that in a regular RED stack at 1.3 cm/s average linear flow velocity. IERB-filled stack resistance was modeled. The model results fit well with experimental data, thereby confirming the effectiveness of the new approach presented here. The net power density is also estimated based on the measured pressure drop and pumping energy model. Both gross and net power density was improved by over 75% at higher flow rate. A net power density of 0.44 W/m(2) was achieved at a cell thickness of 500 MUm. To the best of our knowledge, this research is the first to study the impact of IERB on power generation and establishes a new approach to improving the power performance of a RED system. PMID- 26560233 TI - Shared adversities of children and comic superheroes as resources for promoting resilience: Comic superheroes are an untapped resource for empowering vulnerable children. PMID- 26560234 TI - Child maltreatment and interpersonal relationship among Chinese children with oppositional defiant disorder. AB - Child maltreatment negatively affects children's development and wellbeing. This study investigated the associations between child maltreatment (i.e., emotional neglect, emotional abuse, and physical abuse) and interpersonal functioning, including parent-child relationship, teacher-student relationship, and peer relationships among children with oppositional defiant disorder (ODD). A total of 256 children with ODD and their parents and class master teachers from Mainland China completed questionnaires. Results showed a negative correlation between emotional abuse (parent-reported) and children's interpersonal relationships with parents, teachers, and peers. Emotional neglect and physical abuse were related to poor parent-child relationships. Latent profile analysis revealed three profiles of child maltreatment among children with ODD. ODD children with more severe levels of one type of maltreatment were also more likely to have experienced severe levels of other types of maltreatment. Children with ODD who were in the group of high maltreatment had the poorest quality of interpersonal relationships. Our findings highlight the urgent need to prevent child maltreatment and promote more positive parenting in families with ODD children. PMID- 26560235 TI - Childhood physical abuse and aggression: Shame and narcissistic vulnerability. AB - This study examined narcissistic vulnerability and shame-proneness as potential mediators between childhood physical abuse (CPA) and adult anger and aggression. Participants were 400 undergraduate students, 134 of whom had a history of CPA. All participants completed self-report questionnaires assessing history of CPA, shame-proneness, narcissistic vulnerability, physical aggression, trait anger, and hostility. Results indicated abused participants were more angry and aggressive and experienced higher levels of shame-proneness and narcissistic vulnerability than nonabused participants. Multiple mediation analyses showed that narcissistic vulnerability, but not shame-proneness, partially mediated the relation between abuse and physical aggression. However, narcissistic vulnerability and shame-proneness both emerged as partial mediators between abuse and the anger and hostility variables. These findings suggest that narcissistic vulnerability and shame-proneness may function as mediators of adjustment following childhood maltreatment. Study limitations and recommendations for future research are discussed. PMID- 26560236 TI - NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described. AB - AIM: Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease. METHODS: Direct sequencing of NPHS1 gene in four children was performed. RESULTS: Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in-frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died CONCLUSIONS: Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data. PMID- 26560237 TI - Inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake in healthy Japanese adults. AB - In the event of a nuclear power plant accident, prophylactic administration of potassium iodide (KI) is recommended to prevent thyroid damage due to uptake of radioiodine. To assess the inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake (RAIU) in healthy adults without dietary iodine restriction, single or repeated doses of 10 mg inorganic iodine solution were given to 22 Japanese volunteers, 18 men and 4 women with the mean age of 35.7 years, between 2011 and 2013. Changes in urinary iodine excretion, thyroid function and 24-hour RAIU were also evaluated. The median 24-hour RAIU without iodine restriction was 13% (range, 5-26%). A single-dose of 10 mg inorganic iodine suppressed the median 24-hour RAIU measured one hour after iodine administration to 3% (range, 1-7 %) and, in 90.9% of 22 participants their 24 hour RAIU was < 5%. For seven participants given 10 mg of inorganic iodine daily for 14 days, the median 24-hour RAIU measured at 24 hours after the last administration of iodine was 6% (range, 2-12%), although the inhibitory effect was diminished in two participants. Serum thyroid stimulating hormone concentration was slightly elevated in three participants without decreased serum FT3 and FT4 levels. We conclude that a single-dose of 10 mg inorganic iodine is sufficient to inhibit RAIU in adults, although the inhibitory effect of repeated dose on RAIU is diminished when KI is given once daily. The dose, duration or interval of iodine administration should be evaluated in iodine-sufficient regions in a future. PMID- 26560238 TI - Auditory system of fruit flies. AB - The fruit fly, Drosophila melanogaster, is an invaluable model for auditory research. Advantages of using the fruit fly include its stereotyped behavior in response to a particular sound, and the availability of molecular-genetic tools to manipulate gene expression and cellular activity. Although the receiver type in fruit flies differs from that in mammals, the auditory systems of mammals and fruit flies are strikingly similar with regard to the level of development, transduction mechanism, mechanical amplification, and central projections. These similarities strongly support the use of the fruit fly to study the general principles of acoustic information processing. In this review, we introduce acoustic communication and discuss recent advances in our understanding on hearing in fruit flies. This article is part of a Special Issue entitled . PMID- 26560239 TI - Attentional modulation of informational masking on early cortical representations of speech signals. AB - To recognize speech in a noisy auditory scene, listeners need to perceptually segregate the target talker's voice from other competing sounds (stream segregation). A number of studies have suggested that the attentional demands placed on listeners increase as the acoustic properties and informational content of the competing sounds become more similar to that of the target voice. Hence we would expect attentional demands to be considerably greater when speech is masked by speech than when it is masked by steady-state noise. To investigate the role of attentional mechanisms in the unmasking of speech sounds, event-related potentials (ERPs) were recorded to a syllable masked by noise or competing speech under both active (the participant was asked to respond when the syllable was presented) or passive (no response was required) listening conditions. The results showed that the long-latency auditory response to a syllable (/bi/), presented at different signal-to-masker ratios (SMRs), was similar in both passive and active listening conditions, when the masker was a steady-state noise. In contrast, a switch from the passive listening condition to the active one, when the masker was two-talker speech, significantly enhanced the ERPs to the syllable. These results support the hypothesis that the need to engage attentional mechanisms in aid of scene analysis increases as the similarity (both acoustic and informational) between the target speech and the competing background sounds increases. PMID- 26560240 TI - Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. AB - Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26560241 TI - Quantitative analysis of protein orientation in membrane environments by kinase activity. AB - AgrC is an integral membrane receptor protein with histidine kinase activity in the accessory gene regulator (agr) quorum-sensing system of Staphylococcus aureus. In this study, proteoliposomes were used as a model to investigate AgrC orientation. Many approaches have been described to determine membrane protein orientation, but they are often complicated and time consuming. In this study, AgrC orientation in liposomes was determined by thiol-reactive reagent labeling and a kinase activity assay. Our results suggest use of a kinase activity assay could get an accurate percentage of functional protein orientation and only cost nearly one-sixth of the time compared with the method based on thiol-reactive reagent labeling. We present an effective and rapid method for determining the orientation of membrane protein kinases like AgrC. PMID- 26560242 TI - Smart linkers in polymer-drug conjugates for tumor-targeted delivery. AB - To achieve effective chemotherapy, many types of drug delivery systems have been developed for the specific environments in tumor tissues. Polymer-drug conjugates are increasingly used in tumor therapy due to several significant advantages over traditional delivery systems. In the fabrication of polymer-drug conjugates, a smart linker is an important component that joins two fragments or molecules together and can be cleared by a specific stimulus, which results in targeted drug delivery and controlled release. By regulating the conjugation between the drug and the nanocarriers, stimulus-sensitive systems based on smart linkers can offer high payloads, certified stability, controlled release and targeted delivery. In this review, we summarize the current state of smart linkers (e.g. disulfide, hydrazone, peptide, azo) used recently in various polymer-drug conjugate-based delivery systems with a primary focus on their sophisticated design principles and drug delivery mechanisms as well as in vivo processes. PMID- 26560243 TI - Physical performance and self-report outcomes associated with use of passive, adaptive, and active prosthetic knees in persons with unilateral, transfemoral amputation: Randomized crossover trial. AB - Prosthetic knees are a vital component in an artificial limb. Contemporary knees include passive, (mechanical), adaptive (computerized), or active (motorized) control systems and have the potential to mitigate amputation-related functional impairments and activity limitations. A 14 mo randomized crossover trial was conducted. Participants (n = 12, mean age = 58 yr) were tested under three conditions: passive control (existing knee), adaptive control (Ossur Rheo Knee II), and active control (Ossur Power Knee II). Training and acclimation time were provided to participants in the adaptive and active knees. Outcome measures included indoor tests (Timed Up and Go test [TUG], stairs, and ramp), outdoor tests (walking course and perceived exertion), step activity monitor, self-report surveys (mobility, balance confidence, physical function, fatigue, and general health), and fall incidence. Mixed-effects linear regression modeling was used to evaluate data. Compared with passive control, adaptive control significantly improved comfortable TUG time (difference = 0.91 s, p = 0.001) and reported physical function (difference = 1.26 [T-score], p = 0.03). Active control significantly increased comfortable TUG, fast TUG, and ramp times (difference = 3.02, 2.66, and 0.96 s, respectively, all p < 0.03) and increased balance confidence (difference = 3.77, p = 0.003) compared with passive control. Findings suggest that adaptive knee control may enhance function compared with passive control but that active control can restrict mobility in middle-age or older users with transfemoral amputation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; "Use of Passive, Adaptive, and Active Prosthetic Knees in Persons With Unilateral, Transfemoral Amputation": NCT02219230; https://clinicaltrials.gov/ct2/show/NCT02219230. PMID- 26560245 TI - Trends and Patterns in Reporting of Patient Safety Situations in Transplantation. AB - Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a "culture of safety." The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de-identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self-reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety-related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk. PMID- 26560246 TI - Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction. AB - The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9 membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins. PMID- 26560244 TI - Topoisomerase 2 Alpha Cooperates with Androgen Receptor to Contribute to Prostate Cancer Progression. AB - Overexpression of TOP2A is associated with risk of systemic progression in prostate cancer patients, and higher levels of TOP2A were found in hormone resistant cases. To elucidate the mechanism by which high levels of TOP2A contribute to tumor progression we generated TOP2A overexpressing prostate cancer cell lines. We show that TOP2A promotes tumor aggressiveness by inducing chromosomal rearrangements of genes that contribute to a more invasive phenotype. Anti-androgen treatment alone was ineffective in killing TOP2A overexpressing cells due to activation of an androgen receptor network. TOP2A poisons killed tumor cells more efficiently early in the progression course, while at later stages they provided greater benefit when combined with anti-androgen therapy. Mechanistically, we find that TOP2A enhances androgen signaling by facilitating transcription of androgen responsive genes, thereby promoting tumor cell growth. These studies revealed a relationship between TOP2A and androgen receptor signaling pathway that contributes to prostate cancer progression and confers sensitivity to treatments. PMID- 26560247 TI - Coplanar Oligo(p-phenylenedisilenylene)s as Si?Si Analogues of Oligo(p phenylenevinylene)s: Evidence for Extended pi-Conjugation through the Carbon and Silicon pi-Frameworks. AB - A series of oligo(p-phenylenedisilenylene)s (Si-OPVs 1-4), silicon analogues of oligo(p-phenylenevinylene)s, up to the tetramer have been synthesized and isolated by the introduction of a newly developed protecting group [(HexO)MEind] for improving their solubility. The experimental and theoretical studies of the Si-OPVs 1-4 demonstrate the fully extended pi-conjugation of the Si-OPV main chains. Single crystal X-ray analyses of the monomer 1 and the dimer 2 revealed the highly coplanar Si-OPV backbones facilitating the effective extension of the pi-conjugation, which has further been validated by the significant increases in the absorption maxima from 465 nm for the monomer 1 to 610 nm for the tetramer 4. The absorption maxima exhibit an excellent fit to Meier's equation, leading to the estimation of an effective conjugation length (ECL) of 9 repeat units (nECL = 9) and the absorption maximum of 635 nm for the infinite chain (lambdainfinity = 635 nm). In sharp contrast to other nonemissive disilenes, the Si-OPVs 2-4 show an intense fluorescence from 613 to 668 nm at room temperature with the quantum yields up to 0.48. All the data presented here provide the first evidence for the efficient extended pi-conjugation between the Si?Si double bonds and the carbon pi-electron systems over the entire Si-OPV skeleton. This study reveals the possibility for developing the conjugated disilene pi-systems, in which the Si?Si double bonds would be promising building blocks, significantly optimizing the intrinsic photophysical and electrochemical properties of the carbon-based pi conjugated materials. PMID- 26560248 TI - Pulmonary pressure, telemedicine, and heart failure therapy. PMID- 26560249 TI - Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial. AB - BACKGROUND: In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. METHODS: The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS: Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0.67 [95% CI 0.55-0.80]; p<0.0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0.52 [95% CI 0.40-0.69]; p<0.0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. INTERPRETATION: Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. FUNDING: St Jude Medical Inc. PMID- 26560250 TI - Magnesium stent scaffolds: DREAMS become reality. PMID- 26560251 TI - The Ties that Bind Us. PMID- 26560252 TI - Leading with Integrity--Being Present and Visible. PMID- 26560253 TI - Scholar-in-Residence: An Organizational Capacity-Building Model to Move Evidence to Action. AB - Quality improvement healthcare leaders recognize that striving for excellence is dependent on a multitude of complex and interactive factors. Translating evidence into clinical practice guidelines, evidence-informed decision-making processes, and policy documents does not, however, guarantee that evidence will reach the point-of-care. This article describes an innovative engagement strategy called the Scholar-in-Residence program. The program represents a model of collaboration between a health region and a university, which is intended to build organizational research capacity while simultaneously facilitating quality in hospital care for seniors. We explain the program and provide implementation details with examples to illustrate how the program builds organizational research capacity at the point-of-care, where healthcare is delivered by professionals, and received by patients admitted to a hospital. By explaining the challenges we encountered, others interested in developing research engagement activities in their health region are assisted and pitfalls are avoided. PMID- 26560254 TI - Investing in Point-of-Care Nursing Scholarship: Economic and Ethical Arguments. PMID- 26560255 TI - Teamwork and Patient Care Teams in an Acute Care Hospital. AB - The literature suggests that effective teamwork among patient care teams can positively impact work environment, job satisfaction and quality of patient care. The purpose of this study was to determine the perceived level of nursing teamwork by registered nurses, registered practical nurses, personal support workers and unit clerks working on patient care teams in one acute care hospital in northern Ontario, Canada, and to determine if a relationship exists between the staff scores on the Nursing Teamwork Survey (NTS) and participant perception of adequate staffing. Using a descriptive cross-sectional research design, 600 staff members were invited to complete the NTS and a 33% response rate was achieved (N=200). The participants from the critical care unit reported the highest scores on the NTS, whereas participants from the inpatient surgical (IPS) unit reported the lowest scores. Participants from the IPS unit also reported having less experience, being younger, having less satisfaction in their current position and having a higher intention to leave. A high rate of intention to leave in the next year was found among all participants. No statistically significant correlation was found between overall scores on the NTS and the perception of adequate staffing. Strategies to increase teamwork, such as staff education, among patient care teams may positively influence job satisfaction and patient care on patient care units. PMID- 26560256 TI - Recruitment and Retention in Rural Nursing: It's Still an Issue! AB - A perennial issue for rural and remote communities in Canada and in other parts of the world is access to a healthcare delivery system including healthcare personnel to provide care to their residents. In total, 18% of Canadians live in rural locations but by proportion have fewer healthcare providers compared with urban settings. Relying on a recently completed documentary analysis of published reports and grey literature on rural and remote nursing practice from Canada and around the world, we recognize that recruitment and retention will be a recurring issue. However, a variety of programs and initiatives have been developed to address this age-old problem. A discussion is provided about educational opportunities, financial incentives and enhanced infrastructure that have been developed to address recruitment and retention challenges. Ongoing evaluations of each of these areas are necessary but require cooperation across provincial and national settings. PMID- 26560257 TI - Mentoring from Afar: Nurse Mentor Challenges in the Canadian Armed Forces. AB - There is an integral connection between leadership, mentoring and professional career progression within the nursing profession. The purpose of this article is to examine recommendations and best practices from the literature and provide a basis to construct a formalized successful mentoring dyad program with guidelines on establishing and maintaining a productive mentoring relationship over long distance. Canadian Armed Forces (CAF) nurses practice within a unique domain both domestically and abroad. The military environment incorporates many aspects of mentoring that could benefit significantly by distance interchange. Supported through examining literature within nursing, CAF publications and other professions along with contrasting successful distance mentoring programs, the findings suggest that a top-down, leadership-driven formal mentoring program could be beneficial to CAF nurses. The literature review outlines definitions of terms for mentorship and distance mentoring or e-mentoring. A cross section of technology is now embedded in all work environments with personal communication devices commonplace. Establishing mentoring relationships from afar is practical and feasible. This article provides a guided discussion for nursing leaders, managers and grassroots nurses to implement mentoring programs over distances. The recommendations and findings of this article could have universal applications to isolated nursing environments outside of Canadian military operational frameworks. PMID- 26560258 TI - Management of gallstones and its related complications. AB - The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications. PMID- 26560259 TI - The Mindful Attention Awareness Scale: Further Examination of Dimensionality, Reliability, and Concurrent Validity Estimates. AB - We examined the factor structure and psychometric properties of the Mindful Attention Awareness Scale (MAAS) in a sample of 810 undergraduate students. Using common exploratory factor analysis (EFA), we obtained evidence for a 1-factor solution (41.84% common variance). To confirm unidimensionality of the 15-item MAAS, we conducted a 1-factor confirmatory factor analysis (CFA). Results of the EFA and CFA, respectively, provided support for a unidimensional model. Using differential item functioning analysis methods within item response theory modeling (IRT-based DIF), we found that individuals with high and low levels of nonattachment responded similarly to the MAAS items. Following a detailed item analysis, we proposed a 5-item short version of the instrument and present descriptive statistics and composite score reliability for the short and full versions of the MAAS. Finally, correlation analyses showed that scores on the full and short versions of the MAAS were associated with measures assessing related constructs. The 5-item MAAS is as useful as the original MAAS in enhancing our understanding of the mindfulness construct. PMID- 26560260 TI - A breath of fresh air. PMID- 26560262 TI - Radio interference. PMID- 26560261 TI - Universities' value. PMID- 26560263 TI - China must act decisively to eradicate the ivory trade. PMID- 26560274 TI - Keystone XL decision puts spotlight on US climate politics. PMID- 26560275 TI - Arecibo Observatory director quits after funding row. PMID- 26560276 TI - Uncertainty for UK science ahead of giant spending review. PMID- 26560277 TI - Mega science prize split between 1,377 physicists. PMID- 26560278 TI - Leukaemia success heralds wave of gene-editing therapies. PMID- 26560279 TI - Canada creates science-minister post. PMID- 26560281 TI - Science and sexism: In the eye of the Twitterstorm. PMID- 26560282 TI - New life for pig-to-human transplants. PMID- 26560283 TI - Biological research: Rethink biosafety. PMID- 26560284 TI - CRISPR: A path through the thicket. PMID- 26560288 TI - Drug pollution: industry responds. PMID- 26560289 TI - Twentieth anniversary: Lessons from Madrid for next climate talks. PMID- 26560290 TI - Policy advice: Irked by naivety about policymaking. PMID- 26560291 TI - Drug pollution: Europe responds. PMID- 26560292 TI - Economics: Account for soil as natural capital. PMID- 26560293 TI - Astronomy: A small star with an Earth-like planet. PMID- 26560294 TI - Earth science: Deadly combination. PMID- 26560295 TI - Materials chemistry: Liquefied molecular holes. PMID- 26560297 TI - Biological rhythms: Human sleep before the industrial era. PMID- 26560298 TI - A rocky planet transiting a nearby low-mass star. AB - M-dwarf stars--hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun--are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere. PMID- 26560299 TI - Liquids with permanent porosity. AB - Porous solids such as zeolites and metal-organic frameworks are useful in molecular separation and in catalysis, but their solid nature can impose limitations. For example, liquid solvents, rather than porous solids, are the most mature technology for post-combustion capture of carbon dioxide because liquid circulation systems are more easily retrofitted to existing plants. Solid porous adsorbents offer major benefits, such as lower energy penalties in adsorption-desorption cycles, but they are difficult to implement in conventional flow processes. Materials that combine the properties of fluidity and permanent porosity could therefore offer technological advantages, but permanent porosity is not associated with conventional liquids. Here we report free-flowing liquids whose bulk properties are determined by their permanent porosity. To achieve this, we designed cage molecules that provide a well-defined pore space and that are highly soluble in solvents whose molecules are too large to enter the pores. The concentration of unoccupied cages can thus be around 500 times greater than in other molecular solutions that contain cavities, resulting in a marked change in bulk properties, such as an eightfold increase in the solubility of methane gas. Our results provide the basis for development of a new class of functional porous materials for chemical processes, and we present a one-step, multigram scale-up route for highly soluble 'scrambled' porous cages prepared from a mixture of commercially available reagents. The unifying design principle for these materials is the avoidance of functional groups that can penetrate into the molecular cage cavities. PMID- 26560300 TI - Plate tectonics on the Earth triggered by plume-induced subduction initiation. AB - Scientific theories of how subduction and plate tectonics began on Earth--and what the tectonic structure of Earth was before this--remain enigmatic and contentious. Understanding viable scenarios for the onset of subduction and plate tectonics is hampered by the fact that subduction initiation processes must have been markedly different before the onset of global plate tectonics because most present-day subduction initiation mechanisms require acting plate forces and existing zones of lithospheric weakness, which are both consequences of plate tectonics. However, plume-induced subduction initiation could have started the first subduction zone without the help of plate tectonics. Here, we test this mechanism using high-resolution three-dimensional numerical thermomechanical modelling. We demonstrate that three key physical factors combine to trigger self sustained subduction: (1) a strong, negatively buoyant oceanic lithosphere; (2) focused magmatic weakening and thinning of lithosphere above the plume; and (3) lubrication of the slab interface by hydrated crust. We also show that plume induced subduction could only have been feasible in the hotter early Earth for old oceanic plates. In contrast, younger plates favoured episodic lithospheric drips rather than self-sustained subduction and global plate tectonics. PMID- 26560301 TI - Widespread exploitation of the honeybee by early Neolithic farmers. AB - The pressures on honeybee (Apis mellifera) populations, resulting from threats by modern pesticides, parasites, predators and diseases, have raised awareness of the economic importance and critical role this insect plays in agricultural societies across the globe. However, the association of humans with A. mellifera predates post-industrial-revolution agriculture, as evidenced by the widespread presence of ancient Egyptian bee iconography dating to the Old Kingdom (approximately 2400 BC). There are also indications of Stone Age people harvesting bee products; for example, honey hunting is interpreted from rock art in a prehistoric Holocene context and a beeswax find in a pre-agriculturalist site. However, when and where the regular association of A. mellifera with agriculturalists emerged is unknown. One of the major products of A. mellifera is beeswax, which is composed of a complex suite of lipids including n-alkanes, n alkanoic acids and fatty acyl wax esters. The composition is highly constant as it is determined genetically through the insect's biochemistry. Thus, the chemical 'fingerprint' of beeswax provides a reliable basis for detecting this commodity in organic residues preserved at archaeological sites, which we now use to trace the exploitation by humans of A. mellifera temporally and spatially. Here we present secure identifications of beeswax in lipid residues preserved in pottery vessels of Neolithic Old World farmers. The geographical range of bee product exploitation is traced in Neolithic Europe, the Near East and North Africa, providing the palaeoecological range of honeybees during prehistory. Temporally, we demonstrate that bee products were exploited continuously, and probably extensively in some regions, at least from the seventh millennium cal BC, likely fulfilling a variety of technological and cultural functions. The close association of A. mellifera with Neolithic farming communities dates to the early onset of agriculture and may provide evidence for the beginnings of a domestication process. PMID- 26560302 TI - Oxygen regulation of breathing through an olfactory receptor activated by lactate. AB - Animals have evolved homeostatic responses to changes in oxygen availability that act on different timescales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long-term responses to low oxygen (hypoxia) has been established, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor gene Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that, in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline. PMID- 26560304 TI - Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome. AB - BACKGROUND: Brittle cornea syndrome (BCS) is a rare, generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Recessive mutations in transcription factors ZNF469 and PRDM5 cause BCS. Both transcription factors are suggested to act on a common pathway regulating extracellular matrix genes, particularly fibrillar collagens. We identified bilateral myopic choroidal neovascularization as the presenting feature of BCS in a 26-year-old-woman carrying a novel PRDM5 mutation (p.Glu134*). We performed immunohistochemistry of anterior and posterior segment ocular tissues, as expression of PRDM5 in the eye has not been described, or the effects of PRDM5-associated disease on the retina, particularly the extracellular matrix composition of Bruch's membrane. METHODS: Immunohistochemistry using antibodies against PRDM5, collagens type I, III, and IV was performed on the eyes of two unaffected controls and two patients (both with Delta9-14 PRDM5). Expression of collagens, integrins, tenascin and fibronectin in skin fibroblasts of a BCS patient with a novel p.Glu134* PRDM5 mutation was assessed using immunofluorescence. RESULTS: PRDM5 is expressed in the corneal epithelium and retina. We observe reduced expression of major components of Bruch's membrane in the eyes of two BCS patients with a PRDM5 Delta9-14 mutation. Immunofluorescence performed on skin fibroblasts from a patient with p.Glu134* confirms the generalized nature of extracellular matrix abnormalities in BCS. CONCLUSIONS: PDRM5-related disease is known to affect the cornea, skin and joints. Here we demonstrate, to the best of our knowledge for the first time, that PRDM5 localizes not only in the human cornea, but is also widely expressed in the retina. Our findings suggest that ECM abnormalities in PRDM5-associated disease are more widespread than previously reported. PMID- 26560305 TI - A novel group of diverse Polinton-like viruses discovered by metagenome analysis. AB - BACKGROUND: The rapidly growing metagenomic databases provide increasing opportunities for computational discovery of new groups of organisms. Identification of new viruses is particularly straightforward given the comparatively small size of viral genomes, although fast evolution of viruses complicates the analysis of novel sequences. Here we report the metagenomic discovery of a distinct group of diverse viruses that are distantly related to the eukaryotic virus-like transposons of the Polinton superfamily. RESULTS: The sequence of the putative major capsid protein (MCP) of the unusual linear virophage associated with Phaeocystis globosa virus (PgVV) was used as a bait to identify potential related viruses in metagenomic databases. Assembly of the contigs encoding the PgVV MCP homologs followed by comprehensive sequence analysis of the proteins encoded in these contigs resulted in the identification of a large group of Polinton-like viruses (PLV) that resemble Polintons (polintoviruses) and virophages in genome size, and share with them a conserved minimal morphogenetic module that consists of major and minor capsid proteins and the packaging ATPase. With a single exception, the PLV lack the retrovirus-type integrase that is encoded in the genomes of all Polintons and the Mavirus group of virophages. However, some PLV encode a newly identified tyrosine recombinase integrase that is common in bacteria and bacteriophages and is also found in the Organic Lake virophage group. Although several PLV genomes and individual genes are integrated into algal genomes, it appears likely that most of the PLV are viruses. Given the absence of protease and retrovirus-type integrase, the PLV could resemble the ancestral polintoviruses that evolved from bacterial tectiviruses. Apart from the conserved minimal morphogenetic module, the PLV widely differ in their genome complements but share a gene network with Polintons and virophages, suggestive of multiple gene exchanges within a shared gene pool. CONCLUSIONS: The discovery of PLV substantially expands the emerging class of eukaryotic viruses and transposons that also includes Polintons and virophages. This class of selfish elements is extremely widespread and might have been a hotbed of eukaryotic virus, transposon and plasmid evolution. New families of these elements are expected to be discovered. PMID- 26560306 TI - Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway. AB - AIMS: PTEN-putative kinase 1 (PINK1)-Parkin-mediated mitophagy is crucial for the clearance of damaged mitochondria. However, the mechanisms underlying PINK1 Parkin-mediated mitophagy are not fully understood. The goal of this study is to identify new regulators and to elucidate the regulatory mechanisms of mitophagy. RESULTS: Quantitative mitochondrial proteomic analysis revealed that 63 proteins showed increased levels and 36 proteins showed decreased levels in cells subjected to carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment. Peroxiredoxin 6 (PRDX6 or Prx6), a unique member of the ubiquitous PRDX family, was recruited to depolarized mitochondria. Reactive oxygen species (ROS) generated by CCCP promoted PRDX6 accumulation and PINK1 stabilization in damaged mitochondria and induced mitophagy. In addition, depletion of PRDX6 resulted in the stabilization of PINK1, accumulation of autophagic marker, p62, translocation of Parkin to mitochondria, and lipidation of microtubule-associated protein 1 light chain 3. Furthermore, these events were blocked upon supplementation with antioxidant N-acetyl-l-cysteine or depletion of PINK1. INNOVATION: This is the first study to demonstrate that PRDX6 is the only member of the PRDX family that relocates to damaged mitochondria, where it plays a crucial role in the initial stage of mitophagy by controlling ROS homeostasis. CONCLUSION: ROS induce the recruitment of PRDX6 to mitochondria, where PRDX6 controls ROS homeostasis in the initial step of PINK1-Parkin-mediated mitophagy. Our study provides new insight into the initial regulatory mechanisms of mitophagy and reveals the protective role of PRDX6 in the clearance of damaged mitochondria. PMID- 26560308 TI - Development and validation of risk prediction equations to estimate future risk of blindness and lower limb amputation in patients with diabetes: cohort study. AB - STUDY QUESTION: Is it possible to develop and externally validate risk prediction equations to estimate the 10 year risk of blindness and lower limb amputation in patients with diabetes aged 25-84 years? METHODS: This was a prospective cohort study using routinely collected data from general practices in England contributing to the QResearch and Clinical Practice Research Datalink (CPRD) databases during the study period 1998-2014. The equations were developed using 763 QResearch practices (n=454,575 patients with diabetes) and validated in 254 different QResearch practices (n=142,419) and 357 CPRD practices (n=206,050). Cox proportional hazards models were used to derive separate risk equations for blindness and amputation in men and women that could be evaluated at 10 years. Measures of calibration and discrimination were calculated in the two validation cohorts. STUDY ANSWER AND LIMITATIONS: Risk prediction equations to quantify absolute risk of blindness and amputation in men and women with diabetes have been developed and externally validated. In the QResearch derivation cohort, 4822 new cases of lower limb amputation and 8063 new cases of blindness occurred during follow-up. The risk equations were well calibrated in both validation cohorts. Discrimination was good in men in the external CPRD cohort for amputation (D statistic 1.69, Harrell's C statistic 0.77) and blindness (D statistic 1.40, Harrell's C statistic 0.73), with similar results in women and in the QResearch validation cohort. The algorithms are based on variables that patients are likely to know or that are routinely recorded in general practice computer systems. They can be used to identify patients at high risk for prevention or further assessment. Limitations include lack of formally adjudicated outcomes, information bias, and missing data. WHAT THIS STUDY ADDS: Patients with type 1 or type 2 diabetes are at increased risk of blindness and amputation but generally do not have accurate assessments of the magnitude of their individual risks. The new algorithms calculate the absolute risk of developing these complications over a 10 year period in patients with diabetes, taking account of their individual risk factors. FUNDING, COMPETING INTERESTS, DATA SHARING: JH-C is co-director of QResearch, a not for profit organisation which is a joint partnership between the University of Nottingham and Egton Medical Information Systems, and is also a paid director of ClinRisk Ltd. CC is a paid consultant statistician for ClinRisk Ltd. PMID- 26560309 TI - Use of electronic nicotine delivery systems and other tobacco products among USA adults, 2014: results from a national survey. AB - OBJECTIVES: This study assessed the awareness and use of traditional and novel tobacco products and dual use of cigarettes with electronic nicotine delivery systems (ENDS) among USA adults. METHODS: Data were obtained from the 2014 Tobacco Products and Risk Perceptions Survey of a probability sample of 5717 USA adults conducted June-November, 2014. RESULTS: Use of ENDS varied by demography and by cigarette and other tobacco use. Adults aged 25-34, non-heterosexual adults, and those reporting poorer health reported higher rates of current ENDS use. Current cigarette smokers had much greater odds of ENDS ever use than never smokers, with one-half of all cigarette smokers having used ENDS and 20.7 % currently using them. However, 22.0 % of current ENDS users were former cigarette smokers, and 10.0 % were never cigarette smokers. CONCLUSIONS: Patterns of ENDS use are evolving rapidly and merit continued surveillance. Nearly 10 % of adult ENDS usage is among never smokers. The public health challenge is how to enhance the potential that ENDS can replace combusted tobacco products without expanding nicotine use among youth, long-term ex-smokers, and other vulnerable populations. PMID- 26560310 TI - Seasonal Dynamics of Soil Labile Organic Carbon and Enzyme Activities in Relation to Vegetation Types in Hangzhou Bay Tidal Flat Wetland. AB - Soil labile organic carbon and soil enzymes play important roles in the carbon cycle of coastal wetlands that have high organic carbon accumulation rates. Soils under three vegetations (Phragmites australis, Spartina alterniflora, and Scirpusm mariqueter) as well as bare mudflat in Hangzhou Bay wetland of China were collected seasonally. Seasonal dynamics and correlations of soil labile organic carbon fractions and soil enzyme activities were analyzed. The results showed that there were significant differences among vegetation types in the contents of soil organic carbon (SOC) and dissolved organic carbon (DOC), excepting for that of microbial biomass carbon (MBC). The P. australis soil was with the highest content of both SOC (7.86 g kg-1) and DOC (306 mg kg-1), while the S. mariqueter soil was with the lowest content of SOC (6.83 g kg-1), and the bare mudflat was with the lowest content of DOC (270 mg kg-1). Soil enzyme activities were significantly different among vegetation types except for urease. The P. australis had the highest annual average activity of alkaline phosphomonoesterase (21.4 mg kg-1 h-1), and the S. alterniflora had the highest annual average activities of beta-glycosidase (4.10 mg kg-1 h-1) and invertase (9.81 mg g-1 24h-1); however, the bare mudflat had the lowest activities of alkaline phosphomonoesterase (16.2 mg kg-1 h-1), beta-glycosidase (2.87 mg kg-1 h 1), and invertase (8.02 mg g-1 24h-1). Analysis also showed that the soil labile organic carbon fractions and soil enzyme activities had distinct seasonal dynamics. In addition, the soil MBC content was significantly correlated with the activities of urease and beta-glucosidase. The DOC content was significantly correlated with the activities of urease, alkaline phosphomonoesterase, and invertase. The results indicated that vegetation type is an important factor influencing the spatial-temporal variation of soil enzyme activities and labile organic carbon in coastal wetlands. PMID- 26560312 TI - A log-linear modelling approach to assessing the consistency of ego reports of dyadic outcomes with applications to fertility and sexual partnerships. AB - We propose a log-linear model to assess the consistency of ego reports of dyadic outcomes. We do so specifically in the context where males and females report on shared events, and we demonstrate how inconsistencies can be assessed by using a log-linear model that estimates separate mixing totals for each set of reports. This modelling approach immediately allows us to determine where inconsistencies in reports occur. To demonstrate how our method can be easily implemented for survey data, we apply it to both the 1992 National Health and Social Life Survey and the 2002 National Survey of Family Growth. Our analysis identifies inconsistencies in male and female reports of concurrent partnerships and the number of biological children. PMID- 26560311 TI - Fostering Formal Commutativity Knowledge with Approximate Arithmetic. AB - How can we enhance the understanding of abstract mathematical principles in elementary school? Different studies found out that nonsymbolic estimation could foster subsequent exact number processing and simple arithmetic. Taking the commutativity principle as a test case, we investigated if the approximate calculation of symbolic commutative quantities can also alter the access to procedural and conceptual knowledge of a more abstract arithmetic principle. Experiment 1 tested first graders who had not been instructed about commutativity in school yet. Approximate calculation with symbolic quantities positively influenced the use of commutativity-based shortcuts in formal arithmetic. We replicated this finding with older first graders (Experiment 2) and third graders (Experiment 3). Despite the positive effect of approximation on the spontaneous application of commutativity-based shortcuts in arithmetic problems, we found no comparable impact on the application of conceptual knowledge of the commutativity principle. Overall, our results show that the usage of a specific arithmetic principle can benefit from approximation. However, the findings also suggest that the correct use of certain procedures does not always imply conceptual understanding. Rather, the conceptual understanding of commutativity seems to lag behind procedural proficiency during elementary school. PMID- 26560313 TI - Overexpression of the olive acyl carrier protein gene (OeACP1) produces alterations in fatty acid composition of tobacco leaves. AB - Taking into account that fatty acid (FA) biosynthesis plays a crucial role in lipid accumulation in olive (Olea europaea L.) mesocarp, we investigated the effect of olive acyl carrier protein (ACP) on FA composition by overexpressing an olive ACP cDNA in tobacco plants. The OeACP1.1A cDNA was inserted in the nucleus or in the chloroplast DNA of different tobacco plants, resulting in extensive transcription of the transgenes. The transplastomic plants accumulated lower olive ACP levels in comparison to nuclear-transformed plants. Moreover, the phenotype of the former plants was characterized by pale green/white cotyledons with abnormal chloroplasts, delayed germination and reduced growth. We suggest that the transplastomic phenotype was likely caused by inefficient olive ACP mRNA translation in chloroplast stroma. Conversely, total lipids from leaves of nuclear transformants expressing high olive ACP levels showed a significant increase in oleic acid (18:1) and linolenic acid (18:3), and a concomitant significant reduction of hexadecadienoic acid (16:2) and hexadecatrienoic acid (16:3). This implies that in leaves of tobacco transformants, as likely in the mesocarp of olive fruit, olive ACP not only plays a general role in FA synthesis, but seems to be specifically involved in chain length regulation forwarding the elongation to C18 FAs and the subsequent desaturation to 18:1 and 18:3. PMID- 26560314 TI - Cannabis exposure and risk of testicular cancer: a systematic review and meta analysis. AB - BACKGROUND: The aetiology of testicular cancer remains elusive. In this manuscript, we review the evidence regarding the association between cannabis use and testicular cancer development. METHODS: In this systematic review and meta analysis, we reviewed literature published between 1(st) January 1980 and 13(th) May 2015 and found three case-control studies that investigated the association between cannabis use and development of testicular germ cell tumours (TGCTs). RESULTS/CONCLUSIONS: Using meta-analysis techniques, we observed that a) current, b) chronic, and c) frequent cannabis use is associated with the development of TGCT, when compared to never-use of the drug. The strongest association was found for non-seminoma development--for example, those using cannabis on at least a weekly basis had two and a half times greater odds of developing a non-seminoma TGCT compared those who never used cannabis (OR: 2.59, 95% CI 1.60-4.19). We found inconclusive evidence regarding the relationship between cannabis use and the development of seminoma tumours. It must be noted that these observations were derived from three studies all conducted in the United States; and the majority of data collection occurred during the 1990's. PMID- 26560315 TI - Characterization of a novel metallo-beta-lactamases fold hydrolase from Pelagibacterium halotolerans, a marine halotolerant bacterium isolated from East China Sea. AB - In this study, a novel metallo-beta-lactamases fold hydrolase PH-1 was identified from Pelagibacterium halotolerans B2(T). This novel member of the family Hyphomicrobiaceae was isolated from the East China Sea. In silico analysis demonstrated that PH-1 and its relative homologues cluster in a unique branch and constitute a new subgroup among MBLs. PH-1 was cloned and overexpressed in Escherichia coli BL21 in a soluble form. SDS-PAGE, MALDI-TOF/TOF-MS, and size exclusion chromatography analysis demonstrated that the PH-1 was a monomer with molecular weight of about 29 kDa. Substrate specificity study showed PH-1 preferred penicillin type beta-lactams and exhibited maximum activity toward penicillin-G. Additionally, our experiments also revealed that PH-1 was a halotolerant enzyme since it is active under 4 M NaCl. The enzyme activity of PH 1 was negatively affected by 1 mM Mn(2+) and EDTA. These observations lay a foundation for further study of MBLs from marine bacterium. PMID- 26560316 TI - Using a Lethality Index to Assess Susceptibility of Tribolium confusum and Oryzaephilus surinamensis to Insecticides. AB - We evaluated knockdown caused by four insecticides: alpha-cypermethrin, chlorfenapyr, pirimiphos-methyl and fipronil against adults of Tribolium confusum Jacquelin Duval, the confused flour beetle and Oryzaephilus surinamensis (L.), the sawtoothed grain beetle. Bioassays were conducted on concrete and metal surfaces. Adults of the tested species were exposed on both surfaces treated with the above insecticides at two doses (low and high). Knockdown assessment was done after 15, 30 and 60 min of adult exposure in the treated surfaces. Also, after 1, 3, 5, 7 and 14 d of exposure, a lethality index was calculated with an equation resulting to values from 0 to 100, where 100 indicated complete mortality and 0 complete survival. We also developed a lethality index by ranking each adult on each surface from 0 to 4, 0: adults moved normally, 1: adults were knocked down, but were able to walk for short intervals, 2: adults were knocked down and unable to walk, but with visible movement of antennae etc., 3: adults were knocked down, with very minimal movement of the tarsi and the antennae and 4: adults were dead (no movement). Knockdown of adults immediately after exposure (15-60 min) was higher for pirimiphos-methyl followed by alpha-cypermethrin, for both dose rates tested and species, but only on the metal surface. The lethality index was nearly 100 for all insecticides after 5d of exposure for O. surinamensis, while for T. confusum the adult lethality index was considerably lower for alpha-cypermethrin, suggesting that that recovery from knockdown occurred. Chlorfenapyr was the only insecticide that was more effective on concrete than on metal, while the reverse was noted for the other three insecticides. These results show that knockdown has different levels, which can be used as indicators of insect mortality or recovery. PMID- 26560319 TI - Global Trends in Nanotechnological Approaches for Various Health Issues - Volume II. PMID- 26560318 TI - Use of CLIA-waived point-of-care tests for infectious diseases in community pharmacies in the United States. AB - Review of point-of-care (POC) testing in community pharmacies, availability and specifications of CLIA-waived infectious disease POC tests, and provide recommendations for future community pharmacy POC models in an effort to improve patient outcomes while reducing antibiotic resistance. PubMed and Medscape were searched for the following keywords: infectious disease, community pharmacy, rapid diagnostic tests, rapid assay, and POC tests. All studies utilizing POC tests in community pharmacies for infectious disease were included. Studies, articles, recommendations, and posters were reviewed and information categorized into general implementation of POC testing in community pharmacies, CLIA-waived tests available, Influenza, Group A Streptococcus pharyngitis, Helicobacter pylori, HIV and Hepatitis C. POC testing provides a unique opportunity for community pharmacists to implement collaborative disease management programmes for infectious diseases and reduce over-prescribing of antibiotics and improve patient outcomes through early detection, treatment and/or referral to a specialist. PMID- 26560317 TI - Characterization of secretomes provides evidence for adipose-derived mesenchymal stromal cells subtypes. AB - INTRODUCTION: This study was aimed at deciphering the secretome of adipose derived mesenchymal stromal cells (ADSCs) cultured in standard and hypoxic conditions to reveal proteins, which may be responsible for regenerative action of these cells. METHODS: Human ADSCs were isolated from 10 healthy donors and cultured for 3-4 passages. Cells were serum deprived and cell purity was assessed using multiple cell surface markers. Conditioned media was collected and analyzed using LC-MS with a focus on characterizing secreted proteins. RESULTS: Purity of the ADSC assessed as CD90+/CD73+/CD105+/CD45-/CD31- cells was greater than 99 % and viability was greater than 97 %. More than 600 secreted proteins were detected in conditioned media of ADSCs. Of these 100 proteins were common to all cultures and included key molecules involved in tissue regeneration such as collagens and collagen maturation enzymes, matrix metalloproteases, matricellular proteins, macrophage-colony stimulating factor and pigment epithelium derived factor. Common set of proteins also included molecules, which contribute to regenerative processes but were not previously associated with ADSCs. These included olfactomedin-like 3, follistatin-like 1 and prosaposin. In addition, ADSCs from the different subjects secreted proteins, which were variable between different cultures. These included proteins with neurotrophic activities, which were not previously associated with ADSCs, such as mesencephalic astrocyte derived neurotrophic factor, meteorin and neuron derived neurotrophic factor. Hypoxia resulted in secretion of 6 proteins, the most prominent included EGF-like repeats and discoidin I-like domains 3, adrenomedullin and ribonuclease 4 of RNase A family. It also caused the disappearance of 8 proteins, including regulator of osteogenic differentiation cartilage-associated protein. CONCLUSIONS: Human ADSCs with CD90+/CD73+/CD105+/CD45-/CD31 /PDGFRbeta+/NG2+/CD146+(-) immunophenotype secrete a large array of proteins, the most represented group is comprised of extracellular matrix components. Number of secreted proteins is largely unaffected by prolonged hypoxia. Variability in the secretion of several proteins from cultured ADSCs of individual subjects suggests that these cells exist as a heterogeneous population containing functionally distinct subtypes, which differ in numbers between donors. PMID- 26560320 TI - Nanotechnology in Disease Diagnostic Techniques. AB - Currently the major research highlights of bioengineering and medical technology are directed towards development of improved diagnostic techniques to screen complex diseases. Screening requirements are to identify the cause of illnesses, monitor improvement or progression of the state of diseases such as cancer, cardiovascular or neurodegenerative diseases. Nanotechnology enables the manipulation of materials at nanoscale and has shown potential to enhance sensitivity, selectivity and lower the cost of a diagnosis. The causative biomolecules (DNA, proteins) can be detected by red-shifted absorbance of gold nanoparticles or alteration in the conductance of a nanowire or nanotubes, and deflection of a micro or nano-cantilever. Several types of nanomaterials such as metals, metal-oxides and quantum dots have shown ample advantages over traditional diagnosis, intracellular labeling and visualization of target cells/tissues. Nanotechnology has also opened several avenues which could be further developed to enable enhanced visualization of tissues, cells, DNA and proteins over a point-of-care device. Protein or gene chips created using nanomaterials could further be integrated into a convenient nano-fluidic device for better disease diagnosis. PMID- 26560321 TI - Application of Efficient Nanoparticles for Early Diagnosis and Treatment of Cancer. AB - Cancer is considered as a prevalent cause of human deaths and undoubtedly, is the most complex disease with multiple cellular physiological systems involved. During the last decade, the application of nanotechnological products for cancer treatment has received considerable attention. These sophisticated tools and materials treat cancer though the early diagnosis, the prediction, the prevention and the personalized therapy. This technology enabled the development of nanoscale particles that can be conjugated with one or multiple functional molecules simultaneously. Nanoparticles have the capability to be delivered directly through blood vessels to the tumor site and interact with targeted tumor specific proteins located inside or on the surface of cancer cells, since their size is a hundred to thousand times smaller than cancer cells. In this review, comprehensive outline of all the latest scientific and technological applications such as quantum dots and gold nanoparticles alongside with their applications in cancer diagnosis and treatment have been presented. PMID- 26560322 TI - Applications of Nanotechnology in Diagnostics and Therapeutics of Alzheimer's and Parkinson's Disease. AB - In this paper, an extended review analysis has been presented concerning the developments in brain drug delivery through new and efficient applications of nanotechnology. Modern nanotechnological approaches for the diagnosis and treatment of Alzheimer's and Parkinson's diseases are described along with simultaneous analysis of safety and practical clinical usage of these strategies. PMID- 26560323 TI - An Overview of Current Screening and Management Approaches for Prostate Cancer. AB - Prostate cancer is the fourth leading cause of mortality in Australian men. The prevalence and incidence is increasing in both developed and developing nations, thus there is a need for better screening and management of this disorder. While there is no direct known cause of prostate cancer, management is largely focused on early detection and treatment strategies. Of particular concern is advanced prostate cancer which can manifest as castrate resistant prostate cancer characterized by therapy resistance. This short review outlines the global epidemiology of prostate cancer, clinical manifestations, risk factors, current screening strategies including first line clinical screening as well as the use of circulating biomarkers, and treatment of prostate cancer through mainstream therapeutics as well as the cutting edge peptide and nano-technology based therapeutics that are being implemented or in the process of development to overcome therapeutic obstacles in the treatment of prostate cancer. PMID- 26560324 TI - An Overview on Global Trends in Nanotechnological Approaches for Alzheimer Therapy. AB - Despite extensive research for over two decades, the medical science is yet to assign the exact aetiology and mode of progression of Alzheimer's disease (AD). The modern era of AD drug development began with the proposal of the cholinergic hypothesis of memory impairment. Since then, despite the proposal and phase trials of many therapeutic options, only few drugs have shown some efficacy and safety. The reasons behind this have been many including the ineffectiveness of tested drugs and inadequacy of clinical development methods. In this manuscript, we present an account of modern structural, functional and molecular imaging developed for AD therapy. A comprehensive review of all the current and future treatment options for AD, ranging from cholinergic drugs, NMDA receptor antagonist, immunotherapy, drugs reducing Aβ production, and drugs targeting tau protein and mitochondrial dysfunction has also been provided. However, the failure of all the proposed treatment options to provide a complete cure of AD has been pushing for the need of new therapies. The recent advent of nano-drugs has been proposed to provide crucial breakthroughs in AD therapy. Hence, a detailed outline of the usage and applications of nano-drugs in AD therapy, and outstanding developments in nanodrug metabolism and disposition has been discussed. PMID- 26560325 TI - Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins. AB - Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well characterized sheep-model, we aimed to determine whether long- and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long- and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage. PMID- 26560327 TI - Risk factors associated with the timing of hospital readmission in an underserved low socioeconomic population. AB - OBJECTIVE: Compare risk factors of hospital readmission between 30-, 60- and 90 day readmission groups in a low socioeconomic population. METHODS: Secondary data obtained from the Epic Systems database management system for patients who experienced a 30-, 60- or 90-day hospital readmission between 2006 and 2013. Risk factors analyzed included sex, race/ethnicity, follow-up status, age, BMI, systolic blood pressure, body temperature and pulse rate. Records for 2191 low income patients (u age = 44.5 years; 72.5% female; 10.1% African American, 26.2% Hispanic, 63.7% White) from a central Texas acute health and primary care facility. RESULTS: The amount of time that passed between a patent's initial hospital encounter and a follow-up visit had an effect in predicting both 60-day (OR = 1.055) and 90-day (OR = 1.088) hospital readmission. Patient race/ethnicity had an effect in predicting 90-day readmission. Hispanic patients had a lower likelihood of being readmitted after 90 days than being readmitted after 30 days as compared with White, non-Hispanic patients (OR = 0.688). CONCLUSIONS: Our study suggests that risk factors identified at 30 days are similar to those at 60 and 90 days, with the exception of follow-up status and race/ethnicity. PMID- 26560328 TI - Novel investigational drugs mimicking exercise for the treatment of cachexia. AB - INTRODUCTION: Cachexia is a syndrome characterized by body weight loss, muscle wasting and metabolic abnormalities, that frequently complicates the management of people affected by chronic diseases. No effective therapy is actually available, although several drugs are under clinical evaluation. Altered energy metabolism markedly contributes to the pathogenesis of cachexia; it can be improved by exercise, which is able to both induce anabolism and inhibit catabolism. AREAS COVERED: This review focuses on exercise mimetics and their potential inclusion in combined protocols to treat cachexia. The authors pay with particular reference to the cancer-associated cachexia. EXPERT OPINION: Even though exercise improves muscle phenotype, most patients retain sedentary habits which are quite difficult to disrupt. Moreover, they frequently present with chronic fatigue and comorbidities that reduce exercise tolerance. For these reasons, drugs mimicking exercise could be beneficial to those who are unable to comply with the practice of physical activity. Since some exercise mimetics may exert serious side effects, further investigations should focus on treatments which maintain their effectiveness on muscle phenotype while remaining tolerable at the same time. PMID- 26560326 TI - Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system. AB - BACKGROUND: The acceptability of and retention on extended-release naltrexone (XR NTX), an FDA-approved medication for the treatment of alcohol and opioid use disorders, among persons living with HIV disease (PLH) under criminal justice setting (CJS) supervision has not been evaluated to date. METHODS: Two double blind placebo-controlled randomized trials of XR-NTX for inmates with HIV disease transitioning to the community with (1) alcohol use disorders (AUDs) or (2) opioid use disorders, are underway. Reasons for not accepting XR-NTX and an evaluation of differences in demographic features between those who were retained on study drug and those who did not return for their second injection post release are discussed. RESULTS: 70% of eligible persons consented to participate; almost 90% received their first injection; and almost 60% returned for their first injection after release. Variables found to be associated (p<0.10) with returning for the second injection included: not meeting criteria for hazardous drinking (p=0.035; OR 0.424 (CI 0.191-0.941)); being prescribed antiretroviral therapy (p=0.068; OR 2.170 (CI 0.943-4.992)); expressing experiencing serious depression 30 days prior to incarceration (p=0.068; OR 1.889 (CI 0.955-3.737)); not having a positive cocaine urine screen on the day of release (DOR) (p=0.011; OR 0.258 (CI 0.091-0.729)); and not meeting criteria for an AUD plus any substance use disorder (p=0.068; OR 0.521 (CI 0.259-1.048)). Only positive cocaine urine test on DOR was statistically significant after multivariate regression analyses (p=0.005; OR 0.207 (CI 0.068-0.623)). CONCLUSION: CJS based XR-NTX programs are highly acceptable among PLH, however retention on XR-NTX after release is negatively impacted by relapse to cocaine use. PMID- 26560329 TI - Identification of metabolites of isopropyl 3-(3,4-dihydroxyphenyl)-2 hydroxypropanoate in rats by high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. AB - Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is an investigational new drug having the capacity for treating ailments in cardiovascular and cerebrovascular system. In this work, a rapid and sensitive method using high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF-MS) was developed to reveal the metabolic profile of IDHP in rats after oral administration. The method involved pretreatment of the samples by formic acid methanol solution (v:v, 5:95), chromatographic separation by an Agilent Eclipse XDB-C18 column (150 * 4.6 mm i.d., 5 um) and online identification of the metabolites by Q-TOF-MS equipped with electrospray ionizer. A total of 16 metabolites from IDHP, including 4 phase I metabolites and 12 phase II metabolites, were detected and tentatively identified from rat plasma, urine and feces. Among these metabolites, Danshensu (DSS), a hydrolysis product of IDHP, could be further transformed to 11 metabolites. These results indicated that DSS was the main metabolite of IDHP in rats and the major metabolic pathways of IDHP in vivo were hydrolysis, O-methylation, sulfation, glucuronidation and reduction. The results also demonstrated that renal route was the main pathway of IDHP clearance in rat. The present study provided valuable information for better understanding the efficacy and safety of IDHP. This article is protected by copyright. All rights reserved. PMID- 26560330 TI - Multimodality imaging: Bird's eye view from The European Society of Cardiology Congress 2015 London, August 29-September 2, 2015. PMID- 26560331 TI - A Fuzzy-C-Means-Clustering Approach: Quantifying Chromatin Pattern of Non Neoplastic Cervical Squamous Cells. AB - Despite the effectiveness of Pap-smear test in reducing the mortality rate due to cervical cancer, the criteria of the reporting standard of the Pap-smear test are mostly qualitative in nature. This study addresses the issue on how to define the criteria in a more quantitative and definite term. A negative Pap-smear test result, i.e. negative for intraepithelial lesion or malignancy (NILM), is qualitatively defined to have evenly distributed, finely granular chromatin in the nuclei of cervical squamous cells. To quantify this chromatin pattern, this study employed Fuzzy C-Means clustering as the segmentation technique, enabling different degrees of chromatin segmentation to be performed on sample images of non-neoplastic squamous cells. From the simulation results, a model representing the chromatin distribution of non-neoplastic cervical squamous cell is constructed with the following quantitative characteristics: at the best representative sensitivity level 4 based on statistical analysis and human experts' feedbacks, a nucleus of non-neoplastic squamous cell has an average of 67 chromatins with a total area of 10.827 MUm2; the average distance between the nearest chromatin pair is 0.508 MUm and the average eccentricity of the chromatin is 0.47. PMID- 26560332 TI - Taking culture seriously in biomedical HIV prevention trials: a meta-synthesis of qualitative studies. AB - A substantial gap exists between widespread acknowledgement of the importance of incorporating cultural sensitivity in biomedical HIV prevention trials and empirical evidence to guide the operationalization of cultural sensitivity in these trials. We conducted a systematic literature search and qualitative meta synthesis to explore how culture is conceptualized and operationalized in global biomedical HIV prevention trials. Across 29 studies, the majority (n = 17) were conducted in resource-limited settings. We identified four overarching themes: (1) semantic cultural sensitivity - challenges in communicating scientific terminology into local vernaculars; (2) instrumental cultural sensitivity - understanding historical experiences to guide tailoring of trial activities; (3) budgetary, logistical, and personnel implications of operationalizing cultural sensitivity; and (4) culture as an asset. Future investigations should address how sociocultural considerations are operationalized across the spectrum of trial preparedness, implementation, and dissemination in particular sociocultural contexts, including intervention studies and evaluations of the effectiveness of methods used to operationalize culturally sensitive practices. PMID- 26560333 TI - Effects of polarization induced by non-weak electric fields on the excitability of elongated neurons with active dendrites. AB - An externally-applied electric field can polarize a neuron, especially a neuron with elongated dendrites, and thus modify its excitability. Here we use a computational model to examine, predict, and explain these effects. We use a two compartment Pinsky-Rinzel model neuron polarized by an electric potential difference imposed between its compartments, and we apply an injected ramp current. We vary three model parameters: the magnitude of the applied potential difference, the extracellular potassium concentration, and the rate of current injection. A study of the Time-To-First-Spike (TTFS) as a function of polarization leads to the identification of three regions of polarization strength that have different effects. In the weak region, the TTFS increases linearly with polarization. In the intermediate region, the TTFS increases either sub- or super-linearly, depending on the current injection rate and the extracellular potassium concentration. In the strong region, the TTFS decreases. Our results in the weak and strong region are consistent with experimental observations, and in the intermediate region, we predict novel effects that depend on experimentally-accessible parameters. We find that active channels in the dendrite play a key role in these effects. Our qualitative results were found to be robust over a wide range of inter-compartment conductances and the ratio of somatic to dendritic membrane areas. In addition, we discuss preliminary results where synaptic inputs replace the ramp injection protocol. The insights and conclusions were found to extend from our polarized PR model to a polarized PR model with I h dendritic currents. Finally, we discuss the degree to which our results may be generalized. PMID- 26560334 TI - Dynamic effective connectivity in cortically embedded systems of recurrently coupled synfire chains. AB - As a candidate mechanism of neural representation, large numbers of synfire chains can efficiently be embedded in a balanced recurrent cortical network model. Here we study a model in which multiple synfire chains of variable strength are randomly coupled together to form a recurrent system. The system can be implemented both as a large-scale network of integrate-and-fire neurons and as a reduced model. The latter has binary-state pools as basic units but is otherwise isomorphic to the large-scale model, and provides an efficient tool for studying its behavior. Both the large-scale system and its reduced counterpart are able to sustain ongoing endogenous activity in the form of synfire waves, the proliferation of which is regulated by negative feedback caused by collateral noise. Within this equilibrium, diverse repertoires of ongoing activity are observed, including meta-stability and multiple steady states. These states arise in concert with an effective connectivity structure (ECS). The ECS admits a family of effective connectivity graphs (ECGs), parametrized by the mean global activity level. Of these graphs, the strongly connected components and their associated out-components account to a large extent for the observed steady states of the system. These results imply a notion of dynamic effective connectivity as governing neural computation with synfire chains, and related forms of cortical circuitry with complex topologies. PMID- 26560335 TI - Antibiotic Exposure, Infection, and the Development of Pediatric Psoriasis: A Nested Case-Control Study. AB - IMPORTANCE: Antibiotics disrupt human microbiota and have been associated with several pediatric autoimmune diseases. Psoriasis activity has been linked to group A streptococcal and viral infections. OBJECTIVE: To determine whether antibiotic exposure and infections are independently associated with incident psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS: This nested case control study used data from the Health Improvement Network database, a population-representative electronic health records database from the United Kingdom, from June 27, 1994, through January 15, 2013. Data were analyzed from September 17, 2014, through August 12, 2015. Children aged 1 to 15 years with newly diagnosed psoriasis (n = 845) were compared with age- and sex-matched controls (n = 8450) randomly chosen at the time of psoriasis diagnosis from general practices with at least one case, excluding children with immunodeficiency, inflammatory bowel disease, and juvenile arthritis. EXPOSURES: Systemic antibacterial prescriptions and infections of the skin and other sites within 2 years before psoriasis diagnosis. MAIN OUTCOMES AND MEASURES: Incident psoriasis as determined by validated diagnostic codes. The association of antibiotic exposure and infections with incident psoriasis was determined by conditional logistic regression, adjusting for confounders. RESULTS: After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2 1.7) and other sites (aOR, 1.3; 95% CI, 1.1-1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3-1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9-1.4) were associated with psoriasis. Results were similar when using a lifetime exposure window. Different classes of antibiotics and age of first antibiotic exposure were also not associated with psoriasis. The findings did not substantively change when excluding periods of varying length before diagnosis. CONCLUSIONS AND RELEVANCE: Infections are associated with the development of pediatric psoriasis, but antibiotics do not appear to contribute substantially to that risk. PMID- 26560336 TI - Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-beta-Positive Subjects in the Alzheimer's Disease Continuum. AB - BACKGROUND: Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. OBJECTIVE: We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-beta-positive (Abeta+) subjects in the AD continuum from healthy controls. METHODS: The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Abeta based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. RESULTS: While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Abeta+ subjects in the early disease stages from the Abeta- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Abeta+ subjects from the Abeta- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. CONCLUSION: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Abeta+ subjects across the AD continuum compared with Abeta- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum. PMID- 26560337 TI - Duration of treatment for asymptomatic bacteriuria during pregnancy. AB - BACKGROUND: A previous Cochrane systematic review has shown that antibiotic drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. OBJECTIVES: To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015) and reference lists of identified articles. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with short-course (four- to seven-day) treatments. The risk of bias of trials included in this review was largely unclear, and most trials were at high risk of performance bias. The quality of the evidence was assessed using the GRADE approach. When the any antibiotic agent was used, the 'no cure' rate for asymptomatic bacteriuria in pregnant women was slightly lower for the short course treatment over the single-dose treatment, although there was evidence of statistical heterogeneity (average risk ratio (RR) 1.28, 95% confidence interval (CI) 0.87 to 1.88; women = 1502, studies = 13; I2 = 56%; very low quality evidence). Data from only good quality trials also showed better cure rates with short (four- to seven-day) regimens of the same microbial agent (average RR 1.72, 95% CI 1.27 to 2.33; women = 803, studies = two; I2 = 0%; high quality evidence). There was no clear difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups, whether the same or different microbial agents were used (RR 1.13, 95% CI 0.77 to 1.66; 445 women studies = eight; I2 = 0%; very low quality evidence). Differences were detected for low birthweight babies, favoring a short course (four- to seven-day treatment) of the same microbial agent, although the data come from a single trial (RR 1.65, 95% CI 1.06 to 2.57; 714 women; high quality evidence), but no differences were observed for preterm delivery (RR 1.17, 95% CI 0.77 to 1.78; women = 804; studies = three; I2 = 23%; moderate quality) or pyelonephritis (RR 3.09, 95% CI 0.54 to 17.55; women = 102; studies = two; I2 = 0%; very low quality evidence). Finally, single-dose treatment of any microbial agent was associated with a decrease in reports of 'any side effects' (RR 0.70, 95% CI 0.56 to 0.88; 1460 women, studies = 12; I2 = 9%; low quality evidence). Evidence was downgraded for risk of bias concerns in trials contributing data and for imprecise effect estimates (wide confidence intervals crossing the line of no effect, and in some cases, small studies with few events). AUTHORS' CONCLUSIONS: A single-dose regimen of antibiotics may be less effective than a short-course (four- to seven-day) regimen, but more evidence is needed from large trials measuring important outcomes, such as cure rate. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven day treatment compared with shorter courses of three- or five-day regimens. PMID- 26560338 TI - Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism. AB - A polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to "non-African" chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus. PMID- 26560339 TI - Patterns of Gene Conversion in Duplicated Yeast Histones Suggest Strong Selection on a Coadapted Macromolecular Complex. AB - We find evidence for interlocus gene conversion in five duplicated histone genes from six yeast species. The sequences of these duplicated genes, surviving from the ancient genome duplication, show phylogenetic patterns inconsistent with the well-resolved orthology relationships inferred from a likelihood model of gene loss after the genome duplication. Instead, these paralogous genes are more closely related to each other than any is to its nearest ortholog. In addition to simulations supporting gene conversion, we also present evidence for elevated rates of radical amino acid substitutions along the branches implicated in the conversion events. As these patterns are similar to those seen in ribosomal proteins that have undergone gene conversion, we speculate that in cases where duplicated genes code for proteins that are a part of tightly interacting complexes, selection may favor the fixation of gene conversion events in order to maintain high protein identities between duplicated copies. PMID- 26560340 TI - SynFind: Compiling Syntenic Regions across Any Set of Genomes on Demand. AB - The identification of conserved syntenic regions enables discovery of predicted locations for orthologous and homeologous genes, even when no such gene is present. This capability means that synteny-based methods are far more effective than sequence similarity-based methods in identifying true-negatives, a necessity for studying gene loss and gene transposition. However, the identification of syntenic regions requires complex analyses which must be repeated for pairwise comparisons between any two species. Therefore, as the number of published genomes increases, there is a growing demand for scalable, simple-to-use applications to perform comparative genomic analyses that cater to both gene family studies and genome-scale studies. We implemented SynFind, a web-based tool that addresses this need. Given one query genome, SynFind is capable of identifying conserved syntenic regions in any set of target genomes. SynFind is capable of reporting per-gene information, useful for researchers studying specific gene families, as well as genome-wide data sets of syntenic gene and predicted gene locations, critical for researchers focused on large-scale genomic analyses. Inference of syntenic homologs provides the basis for correlation of functional changes around genes of interests between related organisms. Deployed on the CoGe online platform, SynFind is connected to the genomic data from over 15,000 organisms from all domains of life as well as supporting multiple releases of the same organism. SynFind makes use of a powerful job execution framework that promises scalability and reproducibility. SynFind can be accessed at http://genomevolution.org/CoGe/SynFind.pl. A video tutorial of SynFind using Phytophthrora as an example is available at http://www.youtube.com/watch?v=2Agczny9Nyc. PMID- 26560341 TI - Genetic Adaptation to Climate in White Spruce Involves Small to Moderate Allele Frequency Shifts in Functionally Diverse Genes. AB - Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome.Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs.Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. PMID- 26560342 TI - The Use of (-)-Sparteine/Organolithium Reagents for the Enantioselective Lithiation of 7,8-Dipropyltetrathia[7]helicene: Single and Double Kinetic Resolution Procedures. AB - The effect of organolithium reagent (RLi: R=nBu, iPr, sBu, tBu), solvent (diethyl ether, diethyl ether/THF and MTBE), and stoichiometry on the (-)-sparteine mediated silylation of 7,8-dipropyltetrathia[7]helicene shows that, unusually, substantially more than 0.5 equivalent of RLi (R=iPr, sBu, tBu) and a large excess of (-)-sparteine (R=nBu, sBu) is often needed to achieve substantial conversions and good ee values. With nBuLi, however, just one equivalent of the organolithium reagent is sufficient to obtain high conversions. Our best results were obtained using the convenient tBuLi/(-)-sparteine adduct with which the need for a high (-)-sparteine/RLi ratio can be avoided. Single- and double-kinetic resolution (KR) procedures give enantiopure samples of 2-trimethylsilyl- and 2,13 di(trimethylsilyl)-7,8-dipropyltetrathia[7]helicene and two-step double-KR combining (-)-sparteine/sBuLi and chiral formamides affords the synthetically valuable 2-formyl-7,8-dipropyltetrathia[7]helicene. This is the first use of (-) sparteine for the enantioselective lithiation of helicenes and the first report of tBuLi outperforming sBuLi in a (-)-sparteine-mediated procedure. PMID- 26560344 TI - Scaling the respiratory metabolism to phosphorus relationship in plant seedlings. AB - There are empirical indications of an isometric scaling relationship between plants' respiratory metabolism rates and nitrogen contents. To test the hypothesis that there may be a similar relationship between plants' respiratory metabolism and phosphorus contents we used data obtained from 150 laboratory and field-grown seedlings representing 30 herbaceous species and 20 woody deciduous species. Our results show that whole-plant respiration rates strongly scaled to the 0.81-power of the whole-plant phosphorus content, across wide ranges of growth conditions and functional classifications. Moreover, we also found a similar scaling exponent between whole-plant respiration rates and total nitrogen contents for the same set of samples. The similarities of the metabolic scaling relationships suggest that similar mechanisms may be involved in the transport and storage of phosphorus and nitrogen in plants. PMID- 26560345 TI - Restabilizing attachment to cultural objects. Aesthetics, emotions and biography. AB - The scholarship on aesthetics and materiality has studied how objects help shape identity, social action and subjectivity. Objects, as 'equipment[s] for living' (Luhmann 2000), become the 'obligatory passage points humans have to contend with in order to pursue their projects (Latour 1991). They provide patterns to which bodies can unconsciously latch onto, or help human agents work towards particular states of being (DeNora 2000, 2003). Objects are central in the long term process of taste construction, as any attachment to an object is made out of a delicate equilibrium of mediators, bodies, situations and techniques (Hennion and his collaborators (Hennion and Fouquet 2001; Hennion and Gomart 1999). In all of these accounts objects are the end result of long-term processes of stabilization, in which the actual material object (a musical piece, a sculpture, an art installation, a glass of wine, the oeuvre of Bach as we know it) is both a result and yet a key co-producer of its own generation. Whereas the literature has been generous and detailed in exploring the processes of assembling and sustaining object-centered attachments, it has not sufficiently engaged with what happens when the aesthetic elements of cultural artifacts that have produced emotional resonance are transformed: what do these artifacts morph into? What explains the transition (or not) of different cultural objects? And relatedly, what happens to the key aesthetic qualities that were so central to how the objects had been defined, and to those who have emotionally attached to them? To answer these questions, this article uses as exemplars two different cases of attachment, predicated on the distinctive features of a cultural object--the transcendence of opera and the authenticity of a soccer jersey--that have undergone transformations. PMID- 26560343 TI - Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study. AB - We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean +/- standard error: 9.11 +/- 1.42; n = 43) than healthy controls (2.90 +/- 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 +/- 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 +/- 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 +/- 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI. PMID- 26560346 TI - Technological properties and probiotic potential of Lactobacillus fermentum strains isolated from West African fermented millet dough. AB - BACKGROUND: Throughout Africa, food fermentations are still driven by indigenous microorganisms which influence the nutritional, organoleptic and safety of the final products. However, for improved safety, consistent quality and beneficial health effects, a trend has emerged which involves the isolation of indigenous strains from traditional fermented products to be used as functional starter cultures. These functional starter cultures possess inherent functional characteristics and can contribute to food quality and safety by offering one or more organoleptic, nutritional, technological or health advantage (probiotics). With the aim of selecting potential probiotic starter cultures, Lactobacillus fermentum strains isolated from fermented millet dough were investigated for technological properties and probiotic traits in-vitro. RESULTS: A total of 176 L. fermentum strains were assessed for technological properties including rate of acidification, exopolysaccharide production and amylase activity. Following this, 48 strains showing desirable technological properties were first screened for acid resistance. Sixteen acid resistant strains were assessed for additional probiotic properties including resistance to bile salts, bile salt hydrolysis, antimicrobial property, haemolysis and antibiotics resistance. L. fermentum strains clustered into 3 groups represented by 36 %, 47 % and 17 % as fast, medium and slow acidifiers respectively. About 8 %, 78 % and 14 % of the strains showed strong, weak and no exopolysaccharides production respectively. Amylase activity was generally weak or not detected. After exposure of 48 L. fermentum strains to pH 2.5 for 4 h, 16 strains were considered to be acid resistant. All 16 strains were resistant to bile salt. Four strains demonstrated bile salt hydrolysis. Antimicrobial activity was observed towards Listeria monocytogenes and Staphylococcus aureus but not E. coli and Salmonella enteritidis. Lactobacillus fermentum strains were generally susceptible to antibiotics except 6 strains which showed resistance towards streptomycin, gentamicin and kanamycin. CONCLUSION: In vitro determination of technological and probiotic properties have shown strain specific difference among L. fermentum strains isolated from fermented millet dough. Sixteen (16) L. fermentum strains have been shown to possess desirable technological and probiotic characteristics in vitro. These strains are therefore good candidates for further studies to elucidate their full potential and possible application as novel probiotic starter cultures. PMID- 26560347 TI - Ocelot Population Status in Protected Brazilian Atlantic Forest. AB - Forest fragmentation and habitat loss are detrimental to top carnivores, such as jaguars (Panthera onca) and pumas (Puma concolor), but effects on mesocarnivores, such as ocelots (Leopardus pardalis), are less clear. Ocelots need native forests, but also might benefit from the local extirpation of larger cats such as pumas and jaguars through mesopredator release. We used a standardized camera trap protocol to assess ocelot populations in six protected areas of the Atlantic forest in southeastern Brazil where over 80% of forest remnants are < 50 ha. We tested whether variation in ocelot abundance could be explained by reserve size, forest cover, number of free-ranging domestic dogs and presence of top predators. Ocelot abundance was positively correlated with reserve size and the presence of top predators (jaguar and pumas) and negatively correlated with the number of dogs. We also found higher detection probabilities in less forested areas as compared to larger, intact forests. We suspect that smaller home ranges and higher movement rates in smaller, more degraded areas increased detection. Our data do not support the hypothesis of mesopredator release. Rather, our findings indicate that ocelots respond negatively to habitat loss, and thrive in large protected areas inhabited by top predators. PMID- 26560348 TI - Automated analysis of confocal laser endomicroscopy images to detect head and neck cancer. AB - BACKGROUND: The purpose of this study was to develop an automated image analysis algorithm to discriminate between head and neck cancer and nonneoplastic epithelium in confocal laser endomicroscopy (CLE) images. METHODS: CLE was applied to image head and neck cancer epithelium in vivo. Histopathologic diagnosis from biopsies was used to classify the CLE images offline as cancer or noncancer tissue. The classified images were used to train automated software based on distance map histograms. The performance of the final algorithm was confirmed by "leave 2 patients out" cross-validation and area under the curve (AUC)/receiver operating characteristic (ROC) analysis. RESULTS: Ninety-two CLE videos and 92 biopsies were analyzed from 12 patients. One hundred two frames of classified neoplastic tissue and 52 frames of nonneoplastic tissue were used for cross-validation of the developed algorithm. AUC varied from 0.52 to 0.92. CONCLUSION: The proposed software allows an objective classification of CLE images of head and neck cancer and adjacent nonneoplastic epithelium. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1419-E1426, 2016. PMID- 26560349 TI - Effects of porcine oocytes on the expression levels of transcripts encoding glycolytic enzymes in granulosa cells. AB - Oocytes play critical roles in regulating the expression of transcripts encoding the glycolytic enzymes phosphofructokinase, platelet (PFKP) and lactate dehydrogenase A (LDHA) in granulosa cells in mice, but whether this is the case in pigs or other mammals has not been adequately investigated. Therefore, the aim of this study was to determine whether porcine oocytes regulate the expression levels of these transcripts in granulosa cells in vitro. Porcine cumulus cells expressed higher levels of PFKP and LDHA transcripts than mural granulosa cells (MGCs). However, co-culturing with oocytes had no significant effect on the isolated cumulus cells. While murine oocytes promoted the expression of both Pfkp and Ldha transcripts by murine MGCs, porcine oocytes promoted the expression of only Pfkp, but not Ldha transcripts by murine MGCs. Neither murine nor porcine oocytes affected PFKP and LDHA expression by porcine MGCs. Moreover, in the presence of porcine follicular fluid, porcine oocytes maintained the expression of PFKP, but not LDHA by porcine cumulus cells. Therefore, porcine oocytes are capable of regulating the expression of PFKP but not LDHA in granulosa cells in coordination with unknown factor(s) present in the follicular fluid. PMID- 26560350 TI - The evolution of dual antiplatelet therapy in the setting of acute coronary syndrome: ticagrelor versus clopidogrel. AB - Review of: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Eng J Med 2009; 361(11): 1045-1057. For acute coronary syndrome (ACS), a dual antiplatelet regimen comprised of treatment with aspirin and either P2Y12 adenosine diphosphate receptor antagonists, clopidogrel, prasugrel or ticagrelor is usually employed. This article compares clopidogrel with ticagrelor for the prevention of vascular events and death in broad population of ACS patients ranging from UA, NSTEMI to STEMI, utilizing planned strategies of medical or invasive treatment strategy. PMID- 26560351 TI - Effect of iterative reconstruction on variability and reproducibility of epicardial fat volume quantification by cardiac CT. AB - BACKGROUND: The epicardial fat volume (EFV) measured by cardiac CT has emerged as an important parameter for understanding the pathophysiology of coronary atherosclerosis. OBJECTIVE: We investigated the variability and reproducibility of EFV measurements and evaluated the effect of model-based type iterative reconstruction (M-IR) on measurement results. METHODS: Non-contrast cardiac CT data (tube voltage 120-kVp, tube current time product 32 mAs) of 30 consecutive patients were reconstructed with filtered back projection (FBP), hybrid type iterative reconstruction (H-IR), and M-IR using a slice thickness of 3.0 mm. CT attenuation and image noise was measured for all reconstructions. Two observers independently quantified EFV using semi-automated software and interobserver agreement was evaluated. RESULTS: There was no significant difference in the CT attenuation of the ascending aorta among the three reconstructions. The mean image noise on FBP-, H-IR-, and M-IR images was 48.0 +/- 7.9 HU, 29.6 +/- 4.8 HU, and 9.3 +/- 1.3 HU, respectively; there was a significant difference among all comparison combinations for the three reconstructions (p < 0.01). FBP yielded the highest EFV among the three reconstructions (171.0 +/- 54.9 cm(3) [FBP], 153.8 +/ 53.1 cm(3) [H-IR], and 134.0 +/- 46.4 cm(3) [M-IR]). For all three reconstructions, interobserver correlations were excellent (r = 0.91 [FBP], 0.93 [H-IR], and 0.96 [M-IR]). Interobserver comparisons showed that the lowest Bland Altman limit of agreement was with M-IR (mean difference 2.0 +/- 4.9%, 95% limit of agreement, -24.0 to 28.0%) followed by H-IR (-2.6 +/- 7.1%, -39.8 to 34.6%) and FBP (-0.2 +/- 8.6%, -45.3- to 45.0%). CONCLUSION: For the quantification of epicardial fat by cardiac CT, model-based iterative reconstruction can improve the image quality and lessen measurement variability. PMID- 26560354 TI - Hearing voices: FDA seeks advice from patients. PMID- 26560352 TI - Evolution of Prdm Genes in Animals: Insights from Comparative Genomics. AB - Prdm genes encode transcription factors with a subtype of SET domain known as the PRDF1-RIZ (PR) homology domain and a variable number of zinc finger motifs. These genes are involved in a wide variety of functions during animal development. As most Prdm genes have been studied in vertebrates, especially in mice, little is known about the evolution of this gene family. We searched for Prdm genes in the fully sequenced genomes of 93 different species representative of all the main metazoan lineages. A total of 976 Prdm genes were identified in these species. The number of Prdm genes per species ranges from 2 to 19. To better understand how the Prdm gene family has evolved in metazoans, we performed phylogenetic analyses using this large set of identified Prdm genes. These analyses allowed us to define 14 different subfamilies of Prdm genes and to establish, through ancestral state reconstruction, that 11 of them are ancestral to bilaterian animals. Three additional subfamilies were acquired during early vertebrate evolution (Prdm5, Prdm11, and Prdm17). Several gene duplication and gene loss events were identified and mapped onto the metazoan phylogenetic tree. By studying a large number of nonmetazoan genomes, we confirmed that Prdm genes likely constitute a metazoan-specific gene family. Our data also suggest that Prdm genes originated before the diversification of animals through the association of a single ancestral SET domain encoding gene with one or several zinc finger encoding genes. PMID- 26560353 TI - No Accumulation of Transposable Elements in Asexual Arthropods. AB - Transposable elements (TEs) and other repetitive DNA can accumulate in the absence of recombination, a process contributing to the degeneration of Y chromosomes and other nonrecombining genome portions. A similar accumulation of repetitive DNA is expected for asexually reproducing species, given their entire genome is effectively nonrecombining. We tested this expectation by comparing the whole-genome TE loads of five asexual arthropod lineages and their sexual relatives, including asexual and sexual lineages of crustaceans (Daphnia water fleas), insects (Leptopilina wasps), and mites (Oribatida). Surprisingly, there was no evidence for increased TE load in genomes of asexual as compared to sexual lineages, neither for all classes of repetitive elements combined nor for specific TE families. Our study therefore suggests that nonrecombining genomes do not accumulate TEs like nonrecombining genomic regions of sexual lineages. Even if a slight but undetected increase of TEs were caused by asexual reproduction, it appears to be negligible compared to variance between species caused by processes unrelated to reproductive mode. It remains to be determined if molecular mechanisms underlying genome regulation in asexuals hamper TE activity. Alternatively, the differences in TE dynamics between nonrecombining genomes in asexual lineages versus nonrecombining genome portions in sexual species might stem from selection for benign TEs in asexual lineages because of the lack of genetic conflict between TEs and their hosts and/or because asexual lineages may only arise from sexual ancestors with particularly low TE loads. PMID- 26560355 TI - Regulatory decision-making meets the real world. AB - As patient input in drug development increases and new data sources are tapped, regulators need to organize and ensure the quality of data to inform decision making. PMID- 26560356 TI - A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases. AB - Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development. PMID- 26560357 TI - Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface. AB - Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user's self selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis. PMID- 26560358 TI - AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. AB - The most common form of the childhood neurodegenerative disease late infantile neuronal ceroid lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene. We tested whether TPP1 gene transfer to the ependyma, the epithelial lining of the brain ventricular system, in TPP1 deficient dogs would be therapeutically beneficial. A one-time administration of recombinant adeno-associated virus (rAAV) expressing canine TPP1 (rAAV.caTPP1) resulted in high expression of TPP1 predominantly in ependymal cells and secretion of the enzyme into the cerebrospinal fluid leading to clinical benefit. Diseased dogs treated with rAAV.caTPP1 showed delays in onset of clinical signs and disease progression, protection from cognitive decline, and extension of life span. By immunostaining and enzyme assay, recombinant protein was evident throughout the brain and spinal cord, with correction of the neuropathology characteristic of the disease. This study in a naturally occurring canine model of TPP1 deficiency highlights the utility of AAV transduction of ventricular lining cells to accomplish stable secretion of recombinant protein for broad distribution in the central nervous system and therapeutic benefit. PMID- 26560359 TI - Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment. AB - Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophage-rich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies. PMID- 26560360 TI - Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. AB - Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. PMID- 26560361 TI - Postoperative management of heart failure in pediatric patients. AB - Low cardiac output syndrome (LCOS) is a well-described entity occurring in 25-65% of pediatric patients undergoing open-heart surgery. With judicious intensive care management of LCOS, most patients have an uncomplicated postoperative course, and within 24 h after cardiopulmonary bypass, the cardiac function returns back to baseline. Some patients have severe forms of LCOS not responsive to medical management alone, requiring temporary mechanical circulatory support to prevent end-organ injury and to decrease myocardial stress and oxygen demand. Occasionally, cardiac function does not recover and heart transplantation is necessary. Long-term mechanical circulatory support devices are used as a bridge to transplantation because of limited availability of donor hearts. Experience in usage of continuous flow ventricular assist devices in the pediatric population is increasing. PMID- 26560362 TI - 15-Lipoxygenase inhibitors: a patent review. AB - INTRODUCTION: 15-Lipoxygenases (15-LOXes) are a family of iron-containing proteins that have the capability for unsaturated fatty acid peroxidation in animals and plants. Two types of the enzyme, 15-LOX-1 and 15-LOX-2, have been recognized in mammals to have different abilities in the peroxidation of arachidonic acid and linoleic acid. In mammalians, the critical role of the mentioned enzymes and their metabolites, hydroxyoctadecadienoic acid (HODE), lipoxins and eoxins, in the formation of inflammation, sensitivities, atherosclerosis and some cancers has been demonstrated. AREAS COVERED: This article reviews relevant publications and patents on 15-LOX inhibitors from the points of view of synthesis and biological activities. Herein, based on the chemical structure and pharmacophore moiety, 15-LOX inhibitors are categorized into heterocyclic, phenolic, allyl and allyloxy derivatives. EXPERT OPINION: It is noteworthy that to date no pharmaceutical product from 15-LOX inhibitors has been approved for therapeutic usage. Recently, the role of 15-LOX-1 in obesity, by directly relating 15-LOX-1 expression with the proliferation and hypertrophy of adipose cells, has been reported. Based on the role 15-LOX plays in promoting cancer by amplifying PPARgamma transcription activity, however, it can be claimed that 15-LOX inhibitors will be deemed suitable as chemotherapy agents in the near future. PMID- 26560364 TI - Treatment of olive mill wastewater by photooxidation with ZrO2-doped TiO2 nanocomposite and its reuse capability. AB - Zirconium dioxide (zirconia, ZrO2)-doped TiO2 (TiO2/ZrO2) nanocomposite was used for the photocatalytic oxidation of pollutant parameters [COD components (CODtotal, CODdissolved and CODinert)], polyphenols (catechol, 3-hydroxybenzoic acid, tyrosol and 4-hydroxybenzoic acid) and total polyaromatic amines [aniline, 4-nitroaniline, o-toluidine and o-anisidine] from the olive mill effluent wastewaters at different operational conditions such as at different mass ratios of ZrO2 (50, 25, 14, 10 and 5 wt%) in the TiO2/ZrO2 nanocomposite, at different TiO2/ZrO2 photocatalyst concentrations (1, 4, 15 and 50 mg/L) and pH values (4.0 7.0-10.0) under 300 W UV irradiations, respectively. Under the optimized conditions (pH = 4.6, 15 mg/L ZrO2/TiO2 nanocomposite with a ZrO2 mass ratio of 14 wt%, 300 W UV light, after 60 min photooxidation time, at 21 degrees C), the maximum CODdissolved, total phenol and total aromatic amines photooxidation yields were 99%, 89% and 95%, respectively. High pollutant removal (89%) yields after sequential five times utilization of ZrO2/TiO2 nanocomposite show that this catalyst can be effectively used commercially in the treatment of olive mill effluent. PMID- 26560365 TI - Design of a polarized filtering photonic-crystal fiber with gold-coated air holes. AB - A novel design of a gold-coated photonic-crystal fiber (PCF) is studied by using the finite element method. The cross-section structure of the PCF is composed of a square lattice of air holes in which two air holes are gold coated, and the air hole layout is modified. The resonance strength and the impact of structural parameters of the PCF on the polarization filter characteristics are studied. Numerical results show that the resonance strength and wavelengths are different in two polarized directions. The resonance strengths that we obtain can reach a value of 720 dB/cm at the wavelength of 1.31 MUm. When the fiber length is 400 MUm, the crosstalk can reach a value of 247.2 dB at the wavelength of 1.31 MUm, which can be applied in many polarization filter devices. And when the length of fiber is longer than 200 MUm, the crosstalk is better than 20 dB with wavelength ranges from 1.2 to 2 MUm. Meanwhile, we can realize the filtering effect with a very short fiber. PMID- 26560366 TI - Absolute measurement of laminar shear rate using photon correlation spectroscopy. AB - Measurement of the components of the shear rate tensor S in a fluid provides insight into the properties of that fluid. We detail a refined method for performing direct and absolute measurement of the components of S in a fluid using photon correlation spectroscopy, which we show gives an absolute, accurate, noninvasive measurement of the shear rate from a single measurement at a single location. We demonstrate this method in a cone and plate rheometer, where we obtain measurements of the shear rate of water in 10 s with an absolute accuracy of 2%. PMID- 26560363 TI - Regulation of iron homeostasis by the p53-ISCU pathway. AB - Accumulation of iron in tissues increases the risk of cancer, but iron regulatory mechanisms in cancer tissues are largely unknown. Here, we report that p53 regulates iron metabolism through the transcriptional regulation of ISCU (iron sulfur cluster assembly enzyme), which encodes a scaffold protein that plays a critical role in Fe-S cluster biogenesis. p53 activation induced ISCU expression through binding to an intronic p53-binding site. Knockdown of ISCU enhanced the binding of iron regulatory protein 1 (IRP1), a cytosolic Fe-S protein, to an iron responsive element in the 5' UTR of ferritin heavy polypeptide 1 (FTH1) mRNA and subsequently reduced the translation of FTH1, a major iron storage protein. In addition, in response to DNA damage, p53 induced FTH1 and suppressed transferrin receptor, which regulates iron entry into cells. HCT116 p53(+/+) cells were resistant to iron accumulation, but HCT116 p53(-/-) cells accumulated intracellular iron after DNA damage. Moreover, excess dietary iron caused significant elevation of serum iron levels in p53(-/-) mice. ISCU expression was decreased in the majority of human liver cancer tissues, and its reduced expression was significantly associated with p53 mutation. Our finding revealed a novel role of the p53-ISCU pathway in the maintenance of iron homeostasis in hepatocellular carcinogenesis. PMID- 26560367 TI - Color-fringe pattern profilometry using a generalized phase-shifting algorithm. AB - In order to overcome the limitations of the sequential phase-shifting fringe pattern profilometry for dynamic measurements, a color-channel-based approach is presented. The proposed technique consists of projecting and acquiring a colored image formed by three sinusoidal phase-shifted patterns. Therefore, by using the conventional three-step phase-shifting algorithm, only one color image is required for phase retrieval each time. However, the use of colored fringe patterns leads to a major problem, the color crosstalk, which introduces phase errors when conventional phase-shifting algorithms with fixed phase-shift values are utilized to retrieve the phase. To overcome the crosstalk issue, we propose the use of a generalized phase-shifting algorithm with arbitrary phase-shift values. The simulations and experimental results show that the proposed algorithm can significantly reduce the influence of the color crosstalk. PMID- 26560368 TI - Development and field tests of a narrowband all-reflective spatial heterodyne spectrometer. AB - We describe the design, development, and performance of a narrowband, all reflective, unaliased spatial heterodyne spectrometer (SHS) that has been tested in observations at the focus of the 1.6 m main telescope of the McMath-Pierce solar telescope on Kitt Peak. The all-reflective SHS described herein is a highly robust common-path Fourier transform spectrometer without moving parts that, over a limited spectral region, combines the large field of view and high resolving power characteristic of interference spectrometers but at substantially reduced instrument size and optical tolerances. The self-scanned region of wavelength space and resolving power of the SHS are determined by the beam size, the diffraction grating groove density, the number of detector elements, and the fixed orientation of a set of pilot mirrors. The results presented here represent the first successful implementation of this reflective SHS design for field use. We discuss concepts behind the unaliased reflective SHS design and report the performance of the instrument when used to observe terrestrial airglow and absorption features, the solar spectrum, and the Jovian spectrum near lambda=6300 A, at the achieved resolving power (R=lambda/deltalambda) of R>100,000. The results confirm that reflective SHS instruments can deliver effective interferometric performance in the visible to the far-ultraviolet wavelengths with commercial optics of moderate surface quality. PMID- 26560369 TI - Design of a low-cost and compact 1 * 5 wavelength-selective switch for access networks. AB - This paper describes the design, modeling, construction, and testing of a low cost and compact (80 mm*50 mm) 1*5 wavelength-selective switch. The core beam deflecting element of the switch is a nematic liquid crystal on silicon spatial light modulator. The switch is designed for coarse wavelength-division multiplexing wavelengths in order to bring the benefit of a low-cost, compact, and robust switching design toward the customer end in the access network. During the system development stage, a single optomechanical assembly was designed and prototyped using the three-dimensional printing technology. The experimental results show an insertion loss of -13.8+/-1.4 dB and a worst-case scenario crosstalk level of -24.8 dB. Approaches for enhancing the performance of the switch are analyzed and discussed. PMID- 26560370 TI - Three-dimensional/two-dimensional convertible projection screen using see-through integral imaging based on holographic optical element. AB - We propose a 3D/2D convertible screen using a holographic optical element and angular multiplexing method of volume hologram. The proposed screen, named a multiplexed holographic optical element screen (MHOES), is composed of passive optical components, and displaying modes between 3D and 2D modes are converted according to projection directions. In a recording process, the angular multiplexing method by using two reference waves with different incidence angles enables the functions of 3D and 2D screens to be recorded in a single holographic material. Also, in order to avoid the bulky experimental setup due to adopting different projectors for the 3D and 2D modes, the projection part is realized based on a prism. The designed projection part enables the single projector to present 3D on 2D mode, where the 3D and 2D contents are simultaneously displayed in one scene, without active components. The optical characteristics of MHOES are experimentally analyzed, and displaying experiments with a full-color MHOES are presented in order to verify the 3D/2D convertibility and see-through properties. PMID- 26560371 TI - Gain-coupled distributed feedback laser based on periodic surface anode canals. AB - A single-longitude-mode, broad-stripe, gain-coupled, distributed-feedback laser based on periodic surface anode canals (PSACs) is demonstrated. The PSACs, produced by i-line lithography, enhance the contrast of periodic current density in the active layer without introducing effective photon coupling; calculated grating kappaL is only 0.026. Power of 144.6 mW at 968.8 nm, with spectrum linewidth less than 0.04 nm on every uncoated cleavage facet, is obtained at a current of 1.2 A with a side-mode suppression ratio >29 dB. PMID- 26560372 TI - Simulation of path delay multiplexing-based Fourier transform spectrometer for fiber Bragg grating interrogation. AB - A Fourier transform spectrometer (FTS) used for interrogating a fiber Bragg grating (FBG) consists of a scanning-type interferometer. The FTS has a broad wavelength range of operation and good multiplexing capability. However, it has poor wavelength resolution and interrogation speed. We propose a modification to the FTS using path delay multiplexing to improve the same. Using this method, spatial resolution and interrogation time can be improved by n times by using n path delays. In this paper, simulation results for n=2, 5 are shown. PMID- 26560373 TI - Model-based defect detection on structured surfaces having optically unresolved features. AB - In this paper, we demonstrate, both numerically and experimentally, a method for the detection of defects on structured surfaces having optically unresolved features. The method makes use of synthetic reference data generated by an observational model that is able to simulate the response of the selected optical inspection system to the ideal structure, thereby providing an ideal measure of deviation from nominal geometry. The method addresses the high dynamic range challenge faced in highly parallel manufacturing by enabling the use of low resolution, wide field of view optical systems for defect detection on surfaces containing small features over large regions. PMID- 26560374 TI - Restoration of the near-diffraction-limited response size at heterodyne detection of microholograms, distorted by spherical aberration. AB - Spherical aberrations (SAs) are an important factor in limiting the number of recording layers in a multilayer microholographic data storage scheme. This paper discusses the effect of the restoration of the response size, which makes it possible to decrease considerably the requirement of accuracy for the SA correction of the optical pickup system. The restoration occurs at the heterodyne detection of microholograms distorted by aberrations. The effect of restoring is demonstrated experimentally. A study of the dependence of the microholograms' lateral and longitudinal sizes on the medium depth in which they were formed was carried out. To measure the longitudinal size, a special material containing submicron microspheres was used. The size of the microhologram distorted by aberrations was then compared with the response size obtained at detection. In the last step, a conclusion about the restoration of the response size is made. The multilayer microholograms recording was carried out in iron-doped lithium niobate at a depth range from 70 to 520 MUm. A mathematical model of the microholograms' recording-reading was developed. This model makes it possible to give a qualitative explanation of the processes leading to the restoration of the near-diffraction-limited response size. PMID- 26560375 TI - Toward the complete practicability for the linear-equation dwell time model in subaperture polishing. AB - This study intends to address several problems that are still obstructing the complete practicability of the linear equation dwell time model (LEDTM) used in deterministic subaperture polishing, including memory cost, time cost, arbitrary boundary, and arbitrary tool path. For a large-scale surface error matrix, the memory cost and time cost are two major problems of concern. Here, we present a method that uses the operation of a sparse matrix to build and store the coefficient matrix of the linear equation, which can reduce the memory cost and time cost tens to hundreds of times, thus making LEDTM readily deal with a large scale surface error matrix on a common personal computer, with a time cost of ~1 6 s for a surface error matrix with a scale of 300*300 to 600*600. The compatibility for an arbitrary surface error boundary and tool path is also addressed. Using the proposed method, we believe the LEDTM reaches a complete practicability in engineering. PMID- 26560376 TI - Reducing aberration effect of Fourier transform lens by modifying Fourier spectrum of diffractive optical element in beam shaping optical system. AB - In general, Fourier transform lenses are considered as ideal in the design algorithms of diffractive optical elements (DOEs). However, the inherent aberrations of a real Fourier transform lens disturb the far field pattern. The difference between the generated pattern and the expected design will impact the system performance. Therefore, a method for modifying the Fourier spectrum of DOEs without introducing other optical elements to reduce the aberration effect of the Fourier transform lens is proposed. By applying this method, beam shaping performance is improved markedly for the optical system with a real Fourier transform lens. The experiments carried out with a commercial Fourier transform lens give evidence for this method. The method is capable of reducing the system complexity as well as improving its performance. PMID- 26560377 TI - Suspended-core microstructured fiber for refractometric detection of liquids. AB - A silica suspended-core microstructured optical fiber sensor for detection of liquids, operating at 1550 nm, is analyzed. The sensing principle is based on the evanescent wave overlap into a tested analyte, which is filled via capillary forces into the cladding holes. Validations for analytes in the refractive index range of 1.35-1.43 are carried out with liquid-analyte-filling-length limits being studied both theoretically and experimentally. We prove, for the first time to our knowledge, that an extreme sensitivity of 342.86 dB/RIU and resolution of 4.4*10-5 can be achieved. This sensor represents a high-quality alternative for applications requiring a facile, low-cost solution. PMID- 26560378 TI - Remote measurement of surface roughness, surface reflectance, and body reflectance with LiDAR. AB - Light detection and ranging (LiDAR) intensity data are attracting increasing attention because of the great potential for use of such data in a variety of remote sensing applications. To fully investigate the data potential for target classification and identification, we carried out a series of experiments with typical urban building materials and employed our reconstructed built-in-lab LiDAR system. Received intensity data were analyzed on the basis of the derived bidirectional reflectance distribution function (BRDF) model and the established integration method. With an improved fitting algorithm, parameters involved in the BRDF model can be obtained to depict the surface characteristics. One of these parameters related to surface roughness was converted to a most used roughness parameter, the arithmetical mean deviation of the roughness profile (Ra), which can be used to validate the feasibility of the BRDF model in surface characterizations and performance evaluations. PMID- 26560380 TI - Cryptanalysis of an "asymmetric optical cryptosystem based on coherent superposition and equal modulus decomposition". AB - We analyze and present an attack scheme of the asymmetric optical cryptosystem proposed recently based on coherent superposition and equal modulus decomposition [Opt. Lett.40, 475 (2015)OPLEDP0146-959210.1364/OL.40.000475]. We prove that the attacker can recover the original image with the ciphertext and public keys through the amplitude-phase retrieval algorithm by using two constraints. One constraint of the amplitude-phase retrieval algorithm is the public key and the other is obtained through the analysis of the cryptosystem. The simulation results demonstrate the feasibility of the attack method. PMID- 26560379 TI - General measurement of optical system aberrations with a continuously variable lateral shear ratio by a randomly encoded hybrid grating. AB - A general lateral shearing interferometry method to measure the wavefront aberrations with a continuously variable shear ratio by the randomly encoded hybrid grating (REHG) is proposed. The REHG consists of a randomly encoded binary amplitude grating and a phase chessboard. Its Fraunhofer diffractions contain only four orders which are the +/-1 orders in two orthogonal directions due to the combined modulation of the amplitude and phase. As a result, no orders selection mask is needed for the REHG and the shear ratio is continuously variable, which is beneficial to the variation of sensitivity and testing range for different requirements. To determine the fabrication tolerance of this hybrid grating, the analysis of the effects of different errors on the diffraction intensity distributions is carried out. Experiments have shown that the testing method can achieve a continuously variable shear ratio with the same REHG, and the comparison with a ZYGO GPI interferometer exhibits that the aberration testing method by the REHG is highly precise and also has a good repeatability. This testing method by the REHG is available for general use in testing the aberrations of different optical systems in situ. PMID- 26560381 TI - Component spectra extraction from terahertz measurements of unknown mixtures. AB - The aim of this work is to extract component spectra from unknown mixtures in the terahertz region. To that end, a method, hard modeling factor analysis (HMFA), was applied to resolve terahertz spectral matrices collected from the unknown mixtures. This method does not require any expertise of the user and allows the consideration of nonlinear effects such as peak variations or peak shifts. It describes the spectra using a peak-based nonlinear mathematic model and builds the component spectra automatically by recombination of the resolved peaks through correlation analysis. Meanwhile, modifications on the method were made to take the features of terahertz spectra into account and to deal with the artificial baseline problem that troubles the extraction process of some terahertz spectra. In order to validate the proposed method, simulated wideband terahertz spectra of binary and ternary systems and experimental terahertz absorption spectra of amino acids mixtures were tested. In each test, not only the number of pure components could be correctly predicted but also the identified pure spectra had a good similarity with the true spectra. Moreover, the proposed method associated the molecular motions with the component extraction, making the identification process more physically meaningful and interpretable compared to other methods. The results indicate that the HMFA method with the modifications can be a practical tool for identifying component terahertz spectra in completely unknown mixtures. This work reports the solution to this kind of problem in the terahertz region for the first time, to the best of the authors' knowledge, and represents a significant advance toward exploring physical or chemical mechanisms of unknown complex systems by terahertz spectroscopy. PMID- 26560382 TI - Highly sensitive lateral deformable optical MEMS displacement sensor: anomalous diffraction studied by rigorous coupled-wave analysis. AB - This paper discusses the pulse signal of a highly sensitive lateral deformable optical microelectromechanical systems (MEMS) displacement sensor based on Wood's anomalies and its corresponding tolerance. The optical reflection amplitude of the device changes with the displacement of the nanostructured grating elements. Unexpectedly, the device's original sinusoidal signal develops into a new signal form (i.e., a pulse signal), when the air gap between the two layers of gratings decreases. Since the slope of the pulse signal, namely 2.5%/nm (i.e., 0.65 dB/nm), is eight times higher than that of the original signal form, namely 0.3%/nm (i.e., 0.03 dB/nm), the sensitivity of the structure improves by eight times. However, this device is very sensitive to parameters such as its wavelength, period, duty ratio, and air gap. In this paper we used rigorous coupled wavelength analysis (RCWA) to analyze and optimize the respective influence of each parameter on the device's performance. We have introduced two methods to search for the optimal setting and have demonstrated the optimal settings of different incident lights. The simulation results indicate that it is close to 85% possible to achieve an actual device with the highest slope superior to 0.5%/nm and it is 64% possible that the highest slope of an actual device falls in the interval ranging from 1.0%/nm to 2.0%/nm. All the simulated data helped us better understand the tolerance of the pulse signal and guide us toward the development of an actual device. PMID- 26560383 TI - Step angles to reduce the north-finding error caused by rate random walk with fiber optic gyroscope. AB - We study the relationship between the step angles and the accuracy of north finding with fiber optic gyroscopes. A north-finding method with optimized step angles is proposed to reduce the errors caused by rate random walk (RRW). Based on this method, the errors caused by both angle random walk and RRW are reduced by increasing the number of positions. For when the number of positions is even, we proposed a north-finding method with symmetric step angles that can reduce the error caused by RRW and is not affected by the azimuth angles. Experimental results show that, compared with the traditional north-finding method, the proposed methods with the optimized step angles and the symmetric step angles can reduce the north-finding errors by 67.5% and 62.5%, respectively. The method with symmetric step angles is not affected by the azimuth angles and can offer consistent high accuracy for any azimuth angles. PMID- 26560384 TI - Bidirectional reflection effects in practical integrating spheres. AB - Integrating spheres play a central role in radiometric instrument calibration, surface optical property measurement, and radiant source characterization. Our work involves a simulation, based on the Monte Carlo ray-trace (MCRT) of bidirectional reflections within a practical integrating sphere pierced with two viewing ports. We used data from the literature to create an empirical model for the bidirectional reflection distribution function (BRF) of Spectralon suitable for use in the MCRT environment. The ratio of power escaping through the two openings is shown to vary linearly with wall absorptivity for both diffuse and bidirectional reflections. The sensitivity of this ratio to absorptivity is shown to be less when reflections are weakly bidirectional. PMID- 26560385 TI - Direct welding of glass and metal by 1 kHz femtosecond laser pulses. AB - In the welding process between similar or dissimilar materials, inserting an intermediate layer and pressure assistance are usually thought to be necessary. In this paper, the direct welding between alumina-silicate glass and metal (aluminum, copper, and steel), under exposure from 1 kHz femtosecond laser pulses without any auxiliary processes, is demonstrated. The micron/nanometer-sized metal particles induced by laser ablation were considered to act as the adhesive in the welding process. The welding parameters were optimized by varying the pulse energy and the translation velocity of the sample. The shear joining strength characterized by a shear force testing equipment was as high as 2.34 MPa. This direct bonding technology has potential for applications in medical devices, sensors, and photovoltaic devices. PMID- 26560386 TI - Sky light polarization detection with linear polarizer triplet in light field camera inspired by insect vision. AB - Stable information of a sky light polarization pattern can be used for navigation with various advantages such as better performance of anti-interference, no "error cumulative effect," and so on. But the existing method of sky light polarization measurement is weak in real-time performance or with a complex system. Inspired by the navigational capability of a Cataglyphis with its compound eyes, we introduce a new approach to acquire the all-sky image under different polarization directions with one camera and without a rotating polarizer, so as to detect the polarization pattern across the full sky in a single snapshot. Our system is based on a handheld light field camera with a wide angle lens and a triplet linear polarizer placed over its aperture stop. Experimental results agree with the theoretical predictions. Not only real-time detection but simple and costless architecture demonstrates the superiority of the approach proposed in this paper. PMID- 26560387 TI - Effect of colliding partners on the performance of SF6 and SO2 trace measurements in photoacoustic spectroscopy. AB - A photoacoustic (PA) cell was designed based on the numerical simulation and then was fabricated in order to investigate the effect of various buffer gases on the acoustic signals and the resonant frequencies. The sizes of resonator and buffer chambers were suitably selected to improve signal-to-noise ratio. Atmospheric SF6 impact is high due to its significant green house effect. A series of experiments were performed to detect SF6 trace in the air and various types of rare gases. Similar experiments were carried out for the urban and industrial pollutant SO2 in the same environments. The resonant frequencies were measured at various pressures for several rare gases, namely He, Ne, Ar, Kr, and Xe. The PA spectroscopy of molecular traces in various gases gives rise to sensible spectral shift. It was shown that the use of heavier buffer gases at atmospheric pressure lead to detection of the lower concentrations. In general, the relatively intense acoustic signal is recorded for the heaviest species Xe due to its large vibrational-transitional excitation cross section. Conversely, the light elements dissipate laser energy much larger than the heavy species during the successive collisional excitations. Therefore the trace molecules in helium exhibit a notable rise in the resonant frequency accompanying a small PA signal. PMID- 26560388 TI - Multifocus color image sequence fusion based on mean shift segmentation. AB - This paper presents a region-based technique for fusion of a multifocus color image sequence in the LUV color space. First, mean shift segmentation was applied on the weighted average image of the image sequence to obtain the fusion reference areas. Second, for each segmented area, the well-known modified Laplacian (LAP2) was used as a focus measure to select the clearest parts within the image sequence and then a final image focused with all parts can be generated. Mutual information, QAB/F metric, entropy, standard deviation, image sharpness metric, image contrast metric, average gradient, and spatial frequency were adopted to assess the quality of the fused image. Experiments carried out using standard image sequences from HeliconSoft demonstrated that the results obtained through our technique offer good performance. The proposed technique can be used to extend the depth of field (DOF) of a camera system effectively. PMID- 26560389 TI - Highly transparent light-harvesting window film. AB - We have simulated unique textured window films that capture solar radiation without compromising the window's transparency by scattering infrared light toward photovoltaic strips located at the edges of the window. These films are ideal for powering electrochromic glass, which is difficult to install as each window requires its own power source. Our most promising design consists of an embedded array of 35 degrees cones coated with a five-layer SiO2-Ag stack that was simulated to direct 1.4% of the incident light toward the edges and generate 1 W of power under a collimated 1000 W/m2 AM1.5G source at 60 degrees and an average of 0.5 W over a full year when applied to a 1 m*1 m window. The internal visible transmittance of the window with the applied film is 95% at normal incidence, and remains above 85% for viewing angles up to 60 degrees . The haze is 0.6% at normal incidence and 3.9% at 60 degrees . PMID- 26560390 TI - A reconfigurable all-fiber polarization-diversity coherent Doppler lidar: principles and numerical simulations. AB - This paper shows an efficient adaptation of a polarization diversity optical front-end, commonly used in high-speed fiber-optic communications, in a coherent Doppler lidar (CDL). The adopted architecture can be employed in a modified transceiver design for an all-fiber micropulsed coherent Doppler wind lidar where the performance limits of such systems are pushed beyond the conventionally available wind CDLs. As a result, either a longer measurement range, crucial in clear-air environments with low concentration of aerosols, or a shorter integration time (resulting in a faster scanning) can be achieved. Alternatively, in certain aerosol loading conditions where the presence of nonspherical aerosols is considerable, the system can be reconfigured on the fly to analyze the cross polarization of the backscatter optical signal. The result is the capability to analyze the nature of aerosol particles for the detected range of interest. Due to full utilization of the backscatter signal, i.e., detection of co-polarization and cross polarization components, the signal-to-noise-ratio (SNR) as well as detection range is improved in this configuration. Moreover, the system is capable of providing a more reliable estimation of the aerosol backscatter coefficient when compared with the contemporary CDLs. This system employs robust and compact all-fiber subsystems, which are cost effective and widely available as off-the-shelf components. PMID- 26560391 TI - Monitoring and analysis of thermal deformation waves with a high-speed phase measurement system. AB - Thermal effects in optical substrates are vitally important in determining laser damage resistance in long-pulse and continuous-wave laser systems. Thermal deformation waves in a soda-lime-silica glass substrate have been measured using high-speed interferometry during a series of laser pulses incident on the surface. Two-dimensional images of the thermal waves were captured at a rate of up to six frames per thermal event using a quantitative phase measurement method. The system comprised a Mach-Zehnder interferometer, along with a high-speed camera capable of up to 20,000 frames-per-second. The sample was placed in the interferometer and irradiated with 100 ns, 2 kHz Q-switched pulses from a high power Nd:YAG laser operating at 1064 nm. Phase measurements were converted to temperature using known values of thermal expansion and temperature-dependent refractive index for glass. The thermal decay at the center of the thermal wave was fit to a function derived from first principles with excellent agreement. Additionally, the spread of the thermal distribution over time was fit to the same function. Both the temporal decay fit and the spatial fit produced a thermal diffusivity of 5*10-7 m2/s. PMID- 26560392 TI - Design of an InGaAsP/InP compact integrated optical depolarizer. AB - In this paper, we propose and demonstrate two integrated optics InGaAsP/InP depolarizer circuits. The first one is based on the Lyot depolarizer configuration, while the second one is based on the Mach-Zehnder configuration. Detailed simulation, using three-dimensional full vectorial beam propagation method, shows that a high-index contrast material allows the design of a compact polarization insensitive depolarizer. For the first design, an output degree of polarization (DOP) less than 0.1 is obtained for light sources with spectral widths larger than 25 nm, while for the second one, output DOP less than 0.06 is obtained for light sources with spectral widths larger than 40 nm. PMID- 26560393 TI - Theoretical and experimental investigations on measuring underwater temperature by the coherent Brillouin scattering method. AB - In this paper, a new method of measuring a water-stimulated Brillouin scattering (SBS) frequency shift by optical coherent detection is presented, in order to remote-sense the underwater temperature of the ocean. A single longitudinal mode, passively Q-switched pulsed Nd:YAG laser is used as the light source, the water SBS beam is used as the signal beam, and a portion of the incident laser beam is used as the local oscillator. The heterodyne is detected by a high-speed photodetector, and the heterodyne frequency is the Brillouin frequency shift. Therefore, the underwater temperature can be determined according to the relationship between the Brillouin frequency shift and the water temperature. To test and verify its practicability, the heterodyne waveforms at different water temperatures are recorded in the laboratory with a wide-band oscilloscope, and the Brillouin frequency shifts are deduced by a Fourier transform. The experimental results are consistent with the theoretical analysis. This work provides the foundation for the development of a water temperature measurement system based on coherent Brillouin scattering. PMID- 26560394 TI - Simple and robust algorithm to extend the dynamic range of tip-tilt for a Shack Hartmann sensor. AB - We propose an algorithm to extend the dynamic range of tip-tilt (TT) for a Shack Hartmann wave-front sensor. With this method, the dynamic range of TT is determined by the size of the whole CCD pixel array rather than the size of the sub-aperture. Thus the separate TT sensor in adaptive optics (AO) systems for optical telescope can be saved, which will simplify the systems and enhance the light energy efficiency. The proposed algorithm is computationally effective and appropriate for the real-time TT computation of AO systems. The simulated and experimental results show that the algorithm is robust to realistic scintillation and photon noise and can work well under poor observing conditions. For the given condition with r0 of 5 cm at 550 nm and average flux of 100 photons per sub-aperture, the ultimate measurement accuracy of TT is about 5% pixels (peak-to-valley value). PMID- 26560395 TI - High-speed alternative phase-extraction method for imaging array-coupled binary moire interferometry. AB - An alternative phase-extraction methodology is presented for high-resolution moire analysis, in which the projected and imaged pattern is imaged by a charge coupled device (CCD) array relatively spaced at three pixels per period. The profilometric method uses a photolithographically printed binary pattern with a 33.3% duty cycle symmetrically projected and imaged using telecentric lenses. The resulting surface height map reduces phase error by 33% when compared to conventional sinusoidal projection and extraction methods. The presented system has the ability to resolve surface features with a lateral resolution of <50 MUm and a topographical resolution <10 MUm. PMID- 26560396 TI - Curvature wavefront sensing for the large synoptic survey telescope. AB - The Large Synoptic Survey Telescope (LSST) will use an active optics system (AOS) to maintain alignment and surface figure on its three large mirrors. Corrective actions fed to the LSST AOS are determined from information derived from four curvature wavefront sensors located at the corners of the focal plane. Each wavefront sensor is a split detector such that the halves are 1 mm on either side of focus. In this paper, we describe the extensions to published curvature wavefront sensing algorithms needed to address challenges presented by the LSST, namely the large central obscuration, the fast f/1.23 beam, off-axis pupil distortions, and vignetting at the sensor locations. We also describe corrections needed for the split sensors and the effects from the angular separation of different stars providing the intrafocal and extrafocal images. Lastly, we present simulations that demonstrate convergence, linearity, and negligible noise when compared to atmospheric effects when the algorithm extensions are applied to the LSST optical system. The algorithm extensions reported here are generic and can easily be adapted to other wide-field optical systems including similar telescopes with large central obscuration and off-axis curvature sensing. PMID- 26560397 TI - Encapsulating peritoneal sclerosis: A review of 3 cases. PMID- 26560398 TI - Acute kidney injury secondary to rhabdomyolysis in a nonagenarian patient taking statins. Lessons to be considered. PMID- 26560399 TI - Complete remission of nephrotic syndrome in a woman with renal amyloidosis due to familial mediterranean fever. PMID- 26560400 TI - An uncommon cause of spontaneous hemoperitoneum in a peritoneal dialysis patient. PMID- 26560401 TI - Acute renal colic: Beyond kidney stones. PMID- 26560402 TI - Atypical haemolytic-uraemic syndrome in a young patient with renal, neurological, ocular and cardiovascular involvement. PMID- 26560403 TI - Fullerenes in Aromatic Solvents: Correlation between Solvation-Shell Structure, Solvate Formation, and Solubility. AB - In this work, an all-atom molecular dynamics simulation technique was employed to gain insight into the dynamic structure of the solvation shell formed around C60 and phenyl-C61-butyric acid methyl ester (PCBM) in nine aromatic solvents. A new method was developed to visualize and quantify the distribution of solvent molecule orientations in the solvation shell. A strong positive correlation was found between the regularity of solvent molecule orientations in the solvation shell and the experimentally obtained solubility limits for both C60 and PCBM. This correlation was extended to predict a solubility of 36 g/L for PCBM in 1,2,4 trimethylbenze. The relationship between solvation-shell structure and solubility provided detailed insight into solvate formation of C60 and solvation in relation to solvent molecular structure and properties. The determined dependence of the solvation-shell structure on the geometric shape of the solvent might allow for enhanced control of fullerene solution-phase behavior during processing by chemically tailoring the solvent molecular structure, potentially diminishing the need for costly and environmentally harmful halogenated solvents and/or additives. PMID- 26560404 TI - Oxidative potential of coarse particulate matter (PM(10-2.5)) and its relation to water solubility and sources of trace elements and metals in the Los Angeles Basin. AB - In this study, potential sources of water-soluble (WS) and water-insoluble (WI) fractions of metals and trace elements in coarse particulate matter (CPM) (PM(10 2.5), 2.5 < dp < 10 MUm) were identified and their association with the redox properties of CPM, measured by means of reactive oxygen species (ROS), was explored. CPM was collected during 2012-2013 in Central Los Angeles (LA) and 2013 2014 in Anaheim, CA. Generally, WI components contributed to a larger fraction of CPM ROS activity (as much as 64% and 54% at Central LA and Anaheim, respectively). Two major source factors were identified by principal component analysis for both the WS and WI fractions: vehicular abrasion and re-suspended road dust. Univariate analysis indicated that several species were correlated with CPM ROS activity: in WS fraction, metals such as Mn, Fe, Cd and Zn were associated with WS ROS, while in WI fraction Ti, Fe, Ni, Pb and Cr had the highest correlations with WI ROS activity. Multiple linear regression analysis revealed that both vehicular abrasion and re-suspension of road dust were associated with WS ROS activity, while only vehicular abrasion contributed significantly to the WI ROS activity. Moreover, comparison with previous studies indicated that the ROS activity of CPM has increased in the past 5 years in Central LA. We attribute this increase mainly to the elevated levels of re suspension of road dust caused by the increase in vehicle speed and number of trucks in recent years in this area, reaffirming the growing importance of non tailpipe traffic emissions on CPM toxicity. PMID- 26560405 TI - Assessing the role of physical illness in young old and older old suicide attempters. AB - OBJECTIVES: Attributions for attempting suicide were explored in older adults with and without serious physical illness. METHODS: An open-ended question was used to explore attributions for attempting suicide in 101 hospitalized persons aged 70+. Serious physical illness was defined as a score of 3 or 4 on any of the 13 non-psychiatric organ categories in the Cumulative Illness Rating Scale for Geriatrics. RESULTS: Roughly one-third of hospitalized persons with (22/62) and without (12/39) serious physical illness attributed the suicide attempt to somatic distress. Among 70- to 79-year-olds, seriously physically ill patients were more likely than healthier patients to attribute their attempt to psychological pain (84% vs. 48%, p = 0.013). There were no significant differences in attributions in persons with and without serious health problems in the 80+ group. CONCLUSIONS: The processes by which physical illness confers risk for attempted suicide in older adulthood may be age dependent. Interventions are needed to mitigate psychological pain in physically ill older patients, especially those in their seventies. Research is needed to understand how the psychological processes that influence the desire for suicide change across older adulthood. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26560406 TI - Construct validity of the Free and Cued Selective Reminding Test in older adults with memory complaints. AB - INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is the memory test recommended by the International Working Group on Alzheimer's disease (AD) for the detection of amnestic syndrome of the medial temporal type in prodromal AD. Assessing the construct validity and internal consistency of the Italian version of the FCSRT is thus crucial. METHODS: The FCSRT was administered to 338 community-dwelling participants with memory complaints (57% females, age 74.5 +/- 7.7 years), including 34 with AD, 203 with Mild Cognitive Impairment, and 101 with Subjective Memory Impairment. Internal Consistency was estimated using Cronbach's alpha coefficient. To assess convergent validity, five FCSRT scores (Immediate Free Recall, Immediate Total Recall, Delayed Free Recall, Delayed Total Recall, and Index of Sensitivity of Cueing) were correlated with three well validated memory tests: Story Recall, Rey Auditory Verbal Learning test, and Rey Complex Figure (RCF) recall (partial correlation analysis). To assess divergent validity, a principal component analysis (an exploratory factor analysis) was performed including, in addition to the above-mentioned memory tasks, the following tests: Word Fluencies, RCF copy, Clock Drawing Test, Trail Making Test, Frontal Assessment Battery, Raven Coloured Progressive Matrices, and Stroop Colour-Word Test. RESULTS: Cronbach's alpha coefficients for immediate recalls (IFR and ITR) and delayed recalls (DFR and DTR) were, respectively, .84 and .81. All FCSRT scores were highly correlated with those of the three well-validated memory tests. The factor analysis showed that the FCSRT does not load on the factors saturated by non-memory tests. CONCLUSIONS: These findings indicate that the FCSRT has a good internal consistency and has an excellent construct validity as an episodic memory measure. PMID- 26560407 TI - Effect of emotion on memory for words and their context. AB - Emotion influences various cognitive processes, such as memory. This beneficial or detrimental effect can be studied with verbal material, yet in this case a broad term of context has to be taken into account. The present work reviews recent literature and proposes that traditional differentiation between semantic and environmental context should be replaced with a novel conceptualization of hippocampus-dependent relational memory and item memory (related to the activations of cuneus and left amygdala). Additionally, instead of list-learning paradigms, words should be memorized in the context of sentences or stories for better control over their meaning. The recent evidence suggests that of particular importance for ecological validity in research paradigms is the presence of communicative and social context of verbal material related to such processes as theory of mind and brain activations in temporoparietal junction, posterior cingulate cortex, and dorsal medial prefrontal cortex. We propose that studying memory of verbal material within context gives a better understanding of enhancing and impairing effects of emotion as well as of the underlying brain mechanisms. PMID- 26560408 TI - Maternal healthcare in context: A qualitative study of women's tactics to improve their experience of public healthcare in rural Burkina Faso. AB - Improving the use of public maternal health facilities to prevent maternal death is a priority in developing countries. Accumulating evidence suggests that a key factor in choosing a facility-based delivery is the collaboration and the communication between healthcare providers and women. This article attempts to provide a fine-grained understanding of health system deficiencies, healthcare provider practices and women's experiences with maternal public healthcare. This article presents findings from ethnographic research conducted in the Central East Region of Burkina Faso over a period of eight months (January-August 2013). It is based on monthly interviews with 14 women from village (10) and town (4) and on structured observations of clinical encounters in three primary healthcare facilities (two rural and one urban) (23 days). In addition, 13 health workers were interviewed and 11 focus groups with women from village (6) and town (5) were conducted (48 participants). Guided by an analytic focus on strategies and tactics and drawing on recent discussions on the notion of 'biomedical security', the article explores what tactics women employ in their efforts to maximize their chances of having a positive experience with public maternal healthcare. The synthesis of the cases shows that, in a context of poverty and social insecurity, women employ five tactics: establishing good relations with health workers, being mindful of their 'health booklet', attending prenatal care consultations, minimizing the waiting time at the maternity unit and using traditional medicines. In this way, women strive to achieve biomedical security for themselves and their child and to preserve their social reputation. The study reveals difficulty in the collaboration and communication between health workers and women and suggests that greater attention should be paid to social relations between healthcare providers and users. PMID- 26560409 TI - Complex and dynamic times of being chronically ill: Beyond disease trajectories of patients with ulcerative colitis. AB - This article contributes to health research literature by problematizing the linear, sequential and intelligible understanding of time in the studies of illness. Drawing on the work of Martin Heidegger, it attempts to overcome the problem of considering the time of illness as either a framework controlling patients' experiences or a mind-dependent feature of their lives. The paper offers a conceptual analysis of the stories of ulcerative colitis patients from a recent clinical trial to present temporalities of illness as both objective and subjective, relational and dynamic. We attend to a combination of temporalities related to the ambiguous unfolding of illness and patients' relationships with such an unpredictable world of changing bodies, medical practices and temporal norms. Furthermore, our analysis reveals openness of times and considers ulcerative colitis patients as constantly evolving beings, with multiple possibilities brought about by illness. The paper highlights co-existence of times and considers patients' lives as incorporating a multiplicity of futures, presents and pasts. It concludes with conceptual observations about the consequences of developing complex approaches to illness in health research, which can better highlight the situatedness of patients and their multi dimensional temporal foundations. PMID- 26560410 TI - Avoiding cancer risk information. AB - RATIONALE: Perceived risk for health problems such as cancer is a central construct in many models of health decision making and a target for behavior change interventions. However, some portion of the population actively avoids cancer risk information. The prevalence of, explanations for, and consequences of such avoidance are not well understood. OBJECTIVE: We examined the prevalence and demographic and psychosocial correlates of cancer risk information avoidance preference in a nationally representative sample. We also examined whether avoidance of cancer risk information corresponds with avoidance of cancer screening. RESULTS: Based on our representative sample, 39% of the population indicated that they agreed or strongly agreed that they would "rather not know [their] chance of getting cancer." This preference was stronger among older participants, female participants, and participants with lower levels of education. Preferring to avoid cancer risk information was stronger among participants who agreed with the beliefs that everything causes cancer, that there's not much one can do to prevent cancer, and that there are too many recommendations to follow. Finally, the preference to avoid cancer risk information was associated with lower levels of screening for colon cancer. CONCLUSION: These findings suggest that cancer risk information avoidance is a multi-determined phenomenon that is associated with demographic characteristics and psychosocial individual differences and also relates to engagement in cancer screening. PMID- 26560411 TI - Beyond inequality: Acknowledging the complexity of social determinants of health. AB - The impact of inequality on health is gaining more attention as public and political concern grows over increasing inequality. The income inequality hypothesis, which holds that inequality is detrimental to overall population health, is especially pertinent. However the emphasis on inequality can be challenged on both empirical and theoretical grounds. Empirically, the evidence is contradictory and contested; theoretically, it is inconsistent with our understanding of human societies as complex systems. Research and discussion, both scientific and political, need to reflect better this complexity, and give greater recognition to other social determinants of health. PMID- 26560412 TI - EARLY EVALUATION OF NEW HEALTH TECHNOLOGIES: THE CASE FOR PREMARKET STUDIES THAT HARMONIZE REGULATORY AND COVERAGE PERSPECTIVES. AB - With an increasing awareness that active engagement between policy decision makers, HTA agencies, regulators and payers with industry in the premarket space is needed, a disruptive comprehensive approach is described which moves the evidentiary process exclusively into this space. Single harmonized studies pre market to address regulatory and coverage needs and expectations are more likely to be efficient and less costly and position evidence to drive rather than test innovation. An example of such a process through the MaRS EXCITE program in Ontario, Canada, now undergoing proof of concept, is briefly discussed. Other examples of dialogue between decision makers and industry pre-market are provided though these are less robust than a comprehensive evidentiary approach. PMID- 26560413 TI - Anti-hapten antibodies in response to skin sensitization. AB - Whereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten-specific antibody production. However, there is very limited evidence available for anti-hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti-hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired. PMID- 26560414 TI - Introducing chemical biology applications to introductory organic chemistry students using series of weekly assignments. AB - Calls to bring interdisciplinary content and examples into introductory science courses have increased, yet strategies that involve course restructuring often suffer from the need for a significant faculty commitment to motivate change. Minimizing the need for dramatic course reorganization, the structure, reactivity, and chemical biology applications of classes of biological monomers and polymers have been integrated into introductory organic chemistry courses through three series of semester-long weekly assignments that explored (a) Carbohydrates and Oligosaccharides, (b) Amino Acids, Peptides, and Proteins, and (c) Nucleosides, Nucleotides, and Nucleic Acids. Comparisons of unannounced pre- and post tests revealed improved understanding of a reaction introduced in the assignments, and course examinations evaluated cumulative assignment topics. Course surveys revealed that demonstrating biologically relevant applications consistently throughout the semesters enhanced student interest in the connection between basic organic chemistry content and its application to new and unfamiliar bio-related examples. Covering basic material related to these classes of molecules outside of the classroom opened lecture time to allow the instructor to further build on information developed through the weekly assignments, teaching advanced topics and applications typically not covered in an introductory organic chemistry lecture course. Assignments were implemented as homework, either with or without accompanying discussion, in both laboratory and lecture organic courses within the context of the existing course structures. PMID- 26560415 TI - Is Inflammation a Link Between Self-Reported Health and Infectious Disease Risk? AB - Self-reported health (SRH) has been consistently shown to predict morbidity and mortality. However, the mechanisms underlying this association are poorly understood. The study by Cohen and colleagues reported in this issue of Psychosomatic Medicine fills this gap by examining a potential biological mechanism: alteration of immune system functioning. The study shows that SRH predicted common cold after experimentally controlled virus inoculation in healthy individuals. More specifically, SRH predicted the cold-related illness expression as measured by objective clinical signs, whereas it did not predict the infection rates as measured by predefined increases in specific antibodies. This editorial discusses the significance of this study and the possibility that inflammation, an innate immune response, is a link between SRH and common cold risk. Because the illness expression of cold is generally attributed to increased local inflammation and SRH has been found associated with increased systemic inflammation, it is possible that SRH is a correlate of a heightened systemic inflammatory state and thus leads to increased local inflammatory responses after an exposure to a cold virus. SRH was also associated with well-known risk factors for inflammation in this study, such as overweight, perceived stress, and social isolation. Because of the strong predictive value of SRH for future morbidity and mortality and the simple low-cost tools that enable its assessment, SRH has the potential to identify high-risk individuals in various public health settings. Future research is needed to address the translational applicability of these findings and to further the mechanistic investigation in high-risk groups including older adults. PMID- 26560420 TI - Identification of a New Cell Population Constitutively Circulating in Healthy Conditions and Endowed with a Homing Ability Toward Injured Sites. AB - Stem and progenitor cells are the critical units for tissue maintenance, regeneration, and repair. The activation of regenerative events in response to tissue injury has been correlated with mobilization of tissue-resident progenitor cells, which is functional to the wound healing process. However, until now there has been no evidence for the presence of cells with a healing capacity circulating in healthy conditions. We identified a rare cell population present in the peripheral blood of healthy mice that actively participates in tissue repair. These Circulating cells, with a Homing ability and involved in the Healing process (CH cells), were identified by an innovative flowcytometry strategy as small cells not expressing CD45 and lineage markers. Their transcriptome profile revealed that CH cells are unique and present a high expression of key pluripotency- and epiblast-associated genes. More importantly, CH-labeled cells derived from healthy Red Fluorescent Protein (RFP)-transgenic mice and systemically injected into syngeneic fractured wild-type mice migrated and engrafted in wounded tissues, ultimately differentiating into tissue-specific cells. Accordingly, the number of CH cells in the peripheral blood rapidly decreased following femoral fracture. These findings uncover the existence of constitutively circulating cells that may represent novel, accessible, and versatile effectors of therapeutic tissue regeneration. PMID- 26560421 TI - Escherichia coli ClbS is a colibactin resistance protein. AB - The genomic pks island codes for the biosynthetic machinery that produces colibactin, a peptide-polyketide metabolite. Colibactin is a genotoxin that contributes to the virulence of extra-intestinal pathogenic Escherichia coli and promotes colorectal cancer. In this work, we examined whether the pks-encoded clbS gene of unknown function could participate in the self-protection of E. coli producing colibactin. A clbS mutant was not impaired in the ability to inflict DNA damage in HeLa cells, but the bacteria activated the SOS response and ceased to replicate. This autotoxicity phenotype was markedly enhanced in a clbS uvrB double mutant inactivated for DNA repair by nucleotide excision but was suppressed in a clbS clbA double mutant unable to produce colibactin. In addition, ectopic expression of clbS protected infected HeLa cells from colibactin. Thus, ClbS is a resistance protein blocking the genotoxicity of colibactin both in the procaryotic and the eucaryotic cells. PMID- 26560422 TI - Expression of Sphingosine-1-phosphate (S1P) on the cerebral vasospasm after subarachnoid hemorrhage in rabbits. AB - PURPOSE: To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH). METHODS: The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9. RESULTS: The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9. CONCLUSION: Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH. PMID- 26560423 TI - Improvement of bone repair in diabetic rats subjected to lambda780 nm low-level laser therapy. AB - PURPOSE: To investigate the effect of low-level laser therapy on bone healing in diabetic rats. METHODS: Bone cavities (19 mm diameter) were performed in the femur of 72 alloxan-induced diabetic rats, which were assigned into four groups: CTR (non-diabetic control), DBT (diabetic) CTRL (non-diabetic irradiated) and DBTL (diabetic irradiated). Low-level laser therapy was performed every 48 h for seven days. Animals were euthanized at seven, 18 and 30 days. Alkaline phosphatase serum levels and bone repair were analyzed. RESULTS: Low-level laser therapy significantly increased alkaline phosphatase in at seven and 18 days (p<0.001), and improved bone healing at seven (p<0.01), 18 (p<0.05) and 30 (p<0.01) in diabetic animals. In addition, bone healing in irradiated diabetic group was statistically similar to control group at 30 days (p>0.05). CONCLUSION: Low-level laser therapy increased the serum levels of alkaline phosphatase and improved bone healing in alloxan-induced diabetic rats. PMID- 26560424 TI - Physiological and biochemical measurements before, during and after pregnancy of healthy rats. AB - PURPOSE: To analyze the physiological and biochemical measurements before, during and after pregnancy of healthy rats. METHODS: Wistar adult females rats (n=8) were weighed and blood samples were obtained before, during and after pregnancy for biochemical determinations, chow intake, water consumption and milk production were evaluated. At day 10 postpartum, the rats were killed for weighing of organs and adipose tissues. RESULTS: The results showed increase in body weight, serum insulin and ingestion of water and chow. At day 17 pregnancy, presented normal values in the OGTT. At days 7, 14 and 20 of pregnancy, there was increase in triglyceride levels. At term pregnancy, there was weight gain due to fetal growth. In the postpartum period presented reduced blood glucose levels. The glycemic means were reduced during and after pregnancy compared to after pregnancy. The triglyceride concentrations were increased before and during pregnancy in relation to after pregnancy. The total cholesterol levels presented no changes. CONCLUSION: The use of experimental animals is suitable for evaluation of metabolic changes because the profile of answers found in this study was similar to human profile, showing the relevance of translational research to better understand the pathophysiological mechanisms and possible treatment for diseases. PMID- 26560425 TI - Acute systemic response to intraperitoneal implantation of polypropylene mesh/chitosan-based film composite in pigs. AB - PURPOSE: To assess the systemic response of pigs to the intraperitoneal implantation of polypropylene mesh associated with chitosan-based film with a degree of deacetylation of 95%. METHODS: Blood samples were collected 24 hours before, and two and seven days after surgery. Systemic reactions were evaluated based on white blood cell count, C-reactive protein, and total serum protein, albumin and globulin levels. RESULTS: The systemic response was proportional to the composite response induced by polypropylene mesh, and the tissue inflammatory response was higher in the PP group (p=0.0033). CONCLUSION: The polypropylene mesh/chitosan-based film composite did not elicit a systemic response in pigs. PMID- 26560426 TI - Analysis of the healing process of the wounds occurring in rats using laser therapy in association with hydrocolloid. AB - PURPOSE: To evaluate wound healing in rats by using low-level laser therapy (LLLT) associated with hydrocolloid occlusive dressing. METHODS: Forty male, adult, Wistar rats were used, distributed into four groups: LG (received 2 J/cm2 of laser therapy); HG (treated with hydrocolloid); LHG (treated with 2 J/cm2 of laser therapy and hydrocolloid); and the CG (treated with 1 mL of 0.9% saline). The wound was evaluated at pre-determined periods 3rd and 7th days, considering the macroscopic and histological parameters (inflammatory cells, capillary neoformation, fibroblasts, collagen formation and reepithelialization). RESULTS: The LG group at seven days showed increased collagen formation, the LHG group at 3 days showed mild collagen formation. The HG group and the CG at 7 days showed complete reepithelialization. CONCLUSION: Low-level laser therapy as well as the hydrocolloid dressing have favored the wound-healing process in rats. PMID- 26560427 TI - Effects of nitrofurazone on correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue. AB - PURPOSE: To evaluate the effects of nitrofurazone on the correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue in rats. METHODS: A defect in the abdominal wall was created and corrected with polypropylene mesh in 20 rats. They were randomly distributed into four groups: control, fibrous mesh, nitrofurazone and nitrofurazone dip in the mesh. Euthanasia was performed in 21 post-operative days. The healing process was analyzed regarding the meshes and macroscopic and microscopic aspects. RESULTS: All animals had adhesions. However, no statistically significant difference (p>0.05) when compared between groups. Similarly microscopic analysis, in which there was no statistical significance level for the evaluated parameters such as mono and polymorphonuclear lymphocytes, granuloma, fibrosis, necrosis and collagen proliferation. CONCLUSION: There was no significant effect on the abdominal wall defect repair with polypropylene mesh surrounded by fibrous tissue when dipped in nitrofurazone 2%. PMID- 26560428 TI - Evaluation of systemic inflammatory responses in cholecystectomy by means of access. Single-port umbilical incision, transvaginal NOTES, laparoscopy and laparotomy. AB - PURPOSE: To evaluate and compare clinical and inflammatory responses to the surgical trauma caused by cholecystectomy via several access approaches: single port umbilical incision (SILS), transvaginal natural orifice transluminal endoscopic surgery (NOTES), laparoscopy, and Laparotomy. METHODS: Twenty-eight female pigs were equally divided into four groups and submitted to cholecystectomy by single-port umbilical incision, transvaginal NOTES, laparoscopy, or Laparotomy. An additional five animals served as controls (sham group). Animals were monitored perioperatively regarding anesthesia and surgical procedure times, as well as for the presence of complications. Postoperatively, they were evaluated regarding time to ambulation and feeding, and the presence of clinical events. Procalcitonin, C-reactive protein (CRP), and AQUI feron-gamma (IFN-gamma) measurements were performed before surgery and immediately, two days, and seven days after surgery. Animals were sacrificed and necropsied at seven days after surgery. RESULTS: All procedures were successfully performed as proposed in each group. Only minor complications, such as gallbladder perforation and bleeding from the liver bed, were observed during surgery in all groups. The vaginal NOTES group showed higher anesthesia and surgical procedure times compared to the other groups (p<0.001). No other between-group differences in perioperative or postoperative times, clinical evolution, or serum inflammatory markers were observed. Only adhesions were found on necropsy, with no differences between groups. CONCLUSION: The single-port umbilical and transvaginal NOTES access approaches were feasible and safe compared to laparoscopic and laparotomy for cholecystectomy. PMID- 26560429 TI - Evaluation of intraluminal pressure in cystorrhaphies with and without intestinal serosal patch supplementation from canine cadavers. AB - PURPOSE: To evaluate the maximal intraluminal pressure (MIP) supported by canine cadaveric urinary bladders that underwent cystotomy followed by cystorraphy, with and without serosal patching-supplementation. METHODS: Two groups (n=8 each) were formed, and in one (conventional) the cystotomy was closed with cushing pattern. In the other group (serosal), the same procedure was performed, and a piece of jejunum was used for the construction of the serosal patching over the cystorraphy. MIP was measured by means of an invasive blood pressure transducer with closed stopcock attached to a multiparameter monitor. At the end of each measurement, the bladder body circumference was assessed. RESULTS: Mean +/- SD MIP sustained for the conventional and serosal groups were 28.88 +/- 5.08 and 65.38 +/- 10.99 mmHg, respectively (p < 0.0001). Bladder circumference did not change significantly between groups (p = 0.35) and did not correlate with MIP assessed in conventional (p = 0.27; r = 0.4379) and serosal groups (p = 0.37; r = -0.3637). CONCLUSION: Serosal patch-supplemented cystorraphies were able to sustain intraluminal pressures 55.8% higher, than nonsupplemented cystorraphies in specimens from canine cadavers. PMID- 26560430 TI - Importance of duration and number of ischemic postconditioning cycles in preventing reperfusion mesenteric injuries. Experimental study in rats. AB - PURPOSE: To evaluate the effect of ischemic postconditioning(IPC) on intestinal mucosa of rats subjected to ischemia and reperfusion process comparing two cycles of reperfusion and ischemia lasting two minutes each and four cycles of reperfusion and ischemia lasting 30 seconds each. METHODS: Thirty Wistar rats were distributed into three groups: group A (10 rats), ischemia (30 minutes) and reperfusion (60 minutes); group B (10 rats), ischemia and reperfusion plus IPC by two lasting two minutes each; and Group C (10 rats), ischemia and reperfusion plus IPC by four cycles lasting 30 seconds each. Finally, a segment of small intestine was resected for histological analysis. We analysed the results according to Chiu et al. classification and proceeded to the statistical treatment by Kruskal-Wallis test (p<0.05). RESULTS: The mean degree of tissue injury according to Chiu et al. classification were: Group A, 2.77; in group B, 1.4; and group C, 1.4. B X C (p<0.05). CONCLUSIONS: Ischemic postconditioning was able to minimize reperfusion injury of rats undergone mesenteric ischemia and reperfusion process. There was no difference in the effectiveness of the method comparing two cycles of two minutes with four cycles of 30 seconds by H&E histological evaluation of the ileum after 60-minute reperfusion. PMID- 26560431 TI - Comparative study of collagen deposition in the colon wall of patients operated for sigmoid diverticular disease. AB - PURPOSE: To investigate the deposition of collagen in the colon wall of patients with sigmoid diverticulitis. METHODS: Samples of sigmoid tissue from 15 patients (disease group), seven men and eight women aged 37-77 years who underwent surgery for the treatment of diverticulitis, were selected. For the control group, specimens from five patients, three men and two women aged 19-58 years undergoing emergency surgery for sigmoid trauma were selected. These subjects had no associated diseases. The histological study of the surgical specimens was performed by staining with hematoxylin-eosin and picrosirius and using a histochemical method for collagen quantification. RESULTS: Collagen deposition in the colon wall in terms of area (F), glandular epithelium (E) and total area was significantly higher in the disease group compared to control (p=0.003, p=0.026 and p=0.010, respectively). The collagen volume fraction (F fraction) and muscle tissue (M fraction) were also significantly higher compared to control (p=0.044 and p=0.026, respectively). The muscle (M area) and volume fraction of glandular epithelium (E fraction) did not differ significantly between the two groups, (p=0.074 and p=1.000, respectively). CONCLUSION: In this study, collagen deposition in the colon wall of the patients operated for sigmoid diverticulitis was higher compared to patients without the disease. PMID- 26560432 TI - Fishing in the Water: Effect of Sampled Water Volume on Environmental DNA-Based Detection of Macroinvertebrates. AB - Accurate detection of organisms is crucial for the effective management of threatened and invasive species because false detections directly affect the implementation of management actions. The use of environmental DNA (eDNA) as a species detection tool is in a rapid development stage; however, concerns about accurate detections using eDNA have been raised. We evaluated the effect of sampled water volume (0.25 to 2 L) on the detection rate for three macroinvertebrate species. Additionally, we tested (depending on the sampled water volume) what amount of total extracted DNA should be screened to reduce uncertainty in detections. We found that all three species were detected in all volumes of water. Surprisingly, however, only one species had a positive relationship between an increased sample volume and an increase in the detection rate. We conclude that the optimal sample volume might depend on the species habitat combination and should be tested for the system where management actions are warranted. Nevertheless, we minimally recommend sampling water volumes of 1 L and screening at least 14 MUL of extracted eDNA for each sample to reduce uncertainty in detections when studying macroinvertebrates in rivers and using our molecular workflow. PMID- 26560433 TI - Enhanced visible photocatalytic activity of cotton ball like nano structured Cu doped ZnO for the degradation of organic pollutant. AB - Stringent Environmental standards followed worldwide led to the emergence of advanced oxidation process for the removal of toxic contaminants from water and wastewater. Among all semiconductor photocatalysts have great potential in the degradation of organic and inorganic pollutants into lesser harmful products under visible light irradiations. The present research work describes the synthesis of Cu doped ZnO (CuDZ) via a co-precipitation method to attain high crystallized powder confirmed by XRD analysis. The FE-SEM images showed that the CuDZ has cotton ball like morphology with a uniform size ranged from 25 to 40nm. TEM, FT-IR and UV-DRS studies of the synthesized CuDZ are also discussed in detail. The photocatalytic activity of the as prepared CuDZ catalyst was tested for the degradation of Direct Blue 71 (DB 71) dye in aqueous phase under visible light irradiation. The degree of degradation was found to be dependent on aqueous phase pH, duration of irradiation time, amount of photocatalyst, the initial dye concentration and kinetics of photodegradation. The maximum photocatytic degradation of DB 71 dye was found to be effective at pH 6.8. The optimum amount of photocatalyst was found 3gL-1 of CuDZ for the complete degradation of DB 71 dye (0.01gL-1). The reusability of the photocatalyst indicates that 96% of DB 71 dye was degraded up to 3rd cycles of use. The visible photodegradation of DB 71 dye was exhibited pseudo-first-order kinetics. Chemical oxygen demand and ESI-MS studies confirmed the complete mineralization of DB 71 dye molecules. PMID- 26560434 TI - Chlorpyrifos and Endosulfan degradation studies in an annular slurry photo reactor. AB - TiO2 is one of those compounds which are highly used in photocatalytic degradation of substrates using UV radiation. The substrates are degraded oxidatively and hence finds an important position in advanced oxidation for water/wastewater treatment processes. The thrust of this research was to evaluate the effectiveness of Heterogeneous Photocatalysis (HP) technique, for the removal of pesticides from water/wastewater. The photo-catalytic degradation of two pesticides, widely used in India, viz., Endosulfan (ES) and Chlorpyriphos (CPS) was studied in an annular slurry photo reactor under UVillumination at 254nm. Results revealed that the degradation rate is significantly affected by the initial pesticide concentration, pH of the solution and catalyst concentration. Batch degradation studies on Endosulphan and Chlorpyrifos were conducted in the concentration range from 5 to 25mg/L at a pH ranging from 3.5 to 10.5 and at a catalyst loading of 0.5-2g/L. Endosulphan removal efficiency was about 80-99% and chlorpyrifos removal efficiency was about 84-94%. L-H rate constants were determined using L-H kinetics. High removal efficiencies obtained (80-99%) indicate the effectiveness of this process and its potential for practical application. PMID- 26560435 TI - Xanthogranulomatous pancreatitis associated with a mucinous cystic neoplam. PMID- 26560436 TI - Precordial junctional ST-segment depression with tall symmetric T-waves signifying proximal LAD occlusion, case reports of STEMI equivalence. AB - Timely reperfusion therapy by means of primary percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-segment elevation myocardial infarction. A significant number of patients with large acute myocardial infarction, caused by occlusion of an epicardial coronary artery, do not show ST-elevation on the electrocardiogram. Other ECG abnormalities may be present, the so called STEMI-equivalents. One such STEMI equivalent, junctional ST-segment depression followed by tall symmetrical T-waves in the precordial leads, often in combination with slight ST-elevation in lead AVR, has been associated with proximal occlusion of the left anterior descending coronary artery. Recognition of this ECG pattern by ambulance staff, emergency physicians and interventional cardiologists envolved in STEMI networks, is important to ensure timely reperfusion therapy in these patients. In this paper we present three patients with typical symptoms of acute myocardial infarction and the ECG pattern with slight J-point depression combined with tall, symmetrical T-waves. PMID- 26560437 TI - Guanosine triphosphate can directly regulate cortisol production by activating Ca(2+)-messenger systems in bovine adrenal fasciculata cells. AB - Adenosine triphosphate (ATP) is known to stimulate cortisol production in vitro, however, the effect of guanosine triphosphate (GTP) on cortisol production is not known. We studied the effect of GTP on cortisol production and investigated the regulation of intracellular signal transduction systems, including the cyclic AMP dependent and Ca(2+)-messenger systems, in bovine adrenal fasciculata cells. GTP clearly induced cortisol biosynthesis but only to a level less than half the adrenocorticotropic hormone (ACTH)-induced maximum. The binding site for [gamma (35)S]-GTPgammaS was shown to differ completely from that for ATP and also from those for Gs and Gi, as indicated by the fact that binding was not influenced by pretreatment with cholera toxin and pertussis toxin. GTP significantly increased cytosolic calcium ([Ca(2+)]i) and inositol 1, 4, 5-triphosphate without affecting cyclic AMP formation. GTP-induced cortisol production was suppressed by H-9 and Calphostin C (specific protein kinase C inhibitors) but not by H-8 and KT5720 (specific inhibitors of cyclic AMP-dependent protein kinase), suggesting that GTP activates cortisol biosynthesis possibly via a protein kinase C-dependent pathway. Extracellular calcium may be essential for GTP activity since GTP induced cortisol production was almost completely suppressed in its absence. In conclusion, it can be postulated that GTP-induced steroid secretion in bovine adrenal fasciculata cells is under paracrine or autocrine control. PMID- 26560438 TI - Association of polymorphisms in the ICOS and ICOSL genes with the pathogenesis of autoimmune thyroid diseases. AB - The prognosis of autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), varies among patients. Inducible co-stimulator (ICOS) (CD278) and co-stimulator ligand (ICOSL) (CD275) are important costimulatory molecules. Their interactions play important roles in immune regulation and the pathogenesis of autoimmune diseases through tuning T cell activation, differentiation and function. To clarify the association between ICOS ICOSL signals and AITD, we genotyped single-nucleotide polymorphism (SNP)1 and SNP2 in the ICOS gene and SNP1, SNP2 and SNP3 in the ICOSL gene in 239 HD patients, 232 GD patients, and 129 healthy volunteers (control subjects). There were no differences in genotype and allele frequencies among the three groups, although the frequencies of the AA genotype and A allele of ICOSL SNP2 (rs15927) were slightly, but not significantly, higher in patients with GD, intractable GD, and severe HD than in controls. The mRNA levels of ICOSL were also slightly, but not significantly, lower in individuals with the AA genotype of ICOSL SNP2 than in those with the AG+GG genotypes. In conclusion, the ICOS and ICOSL SNPs examined in this study do not have an apparent effect on the disease susceptibility and prognosis of AITDs. PMID- 26560439 TI - Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-kappaB and JNK/p38 MAPK. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xanthii fructus (XF) has long been used to treat a variety of inflammatory conditions in Korean traditional medicine, but the underlying mechanisms that could explain the anti-inflammatory actions of XF remain largely unknown. AIM OF THE STUDY: This study aimed to elucidate the anti inflammatory effects of X. fructus (XF) and to examine its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MATERIALS AND METHODS: The effect of XF on LPS-induced mRNA and protein expressions of inflammatory mediators and cytokines were determined. Moreover, the activation of the nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways and the expression of heme oxygenase-1 (HO-1) were explored to elucidate the anti-inflammatory mechanisms. RESULTS: XF significantly inhibited LPS-induced production of inflammatory mediators, interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2), without any cytotoxicity. However, it did not affect tissue necrosis factor (TNF)-alpha or IL 1beta production in LPS-stimulated RAW 264.7 cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA and protein were inhibited dose dependently by XF in LPS-stimulated RAW 264.7 cells, but there were no changes in cyclooxygenase-2 (COX-2) mRNA and protein. XF significantly attenuated LPS induced phosphorylation and degradation of inhibitory kappa Balpha (IkappaBalpha) and consequently reduced the nuclear translocation of p65 NF-kappaB. Pretreatment with XF also strongly inhibited the LPS-induced phosphorylation of p38 kinase and JNK, whereas the phosphorylation of ERK1/2 was not affected. In addition, XF led to an increase in HO-1 expression. CONCLUSION: Taken together, our findings support that XF inhibits LPS-induced inflammatory responses by blocking NF-kappaB activation, inhibiting JNK/p38 MAPK phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that it could be an attractive therapeutic candidate for various inflammatory diseases. PMID- 26560440 TI - Chemically defined media modifications to lower tryptophan oxidation of biopharmaceuticals. AB - Oxidation of biopharmaceuticals is a major product quality issue with potential impacts on activity and immunogenicity. At Eli Lilly and Company, high tryptophan oxidation was observed for two biopharmaceuticals in development produced in Chinese hamster ovary cells. A switch from historical hydrolysate-containing media to chemically defined media with a reformulated basal powder was thought to be responsible, so mitigation efforts focused on media modification. Shake flask studies identified that increasing tryptophan, copper, and manganese and decreasing cysteine concentrations were individual approaches to lower tryptophan oxidation. When amino acid and metal changes were combined, the modified formulation had a synergistic impact that led to substantially less tryptophan oxidation for both biopharmaceuticals. Similar results were achieved in shake flasks and benchtop bioreactors, demonstrating the potential to implement these modifications at manufacturing scale. The modified formulation did not negatively impact cell growth and viability, product titer, purity, charge variants, or glycan profile. A potential mechanism of action is presented for each amino acid or metal factor based on its role in oxidation chemistry. This work served not only to mitigate the tryptophan oxidation issue in two Lilly biopharmaceuticals in development, but also to increase our knowledge and appreciation for the impact of media components on product quality. PMID- 26560441 TI - National compliance to an evidence-based multidisciplinary guideline on pancreatic and periampullary carcinoma. AB - BACKGROUND: We evaluated national compliance to selected quality indicators from the Dutch multidisciplinary evidence-based guideline on pancreatic and periampullary carcinoma and identified areas for improvement. METHODS: Compliance to 3 selected quality indicators from the guideline was evaluated before and after implementation of the guideline in 2011: 1) adjuvant chemotherapy after tumor resection for pancreatic carcinoma, 2) discussion of the patient within a multidisciplinary team (MDT) meeting and 3) a maximum 3-week interval between final MDT meeting and start of treatment. RESULTS: In total 5086 patients with pancreatic or periampullary carcinoma were included. In 2010, 2522 patients were included and in 2012, 2564 patients. 1) Use of adjuvant chemotherapy following resection for pancreatic carcinoma increased significantly from 45% (120 out of 268) in 2010 to 54% (182 out of 336) in 2012 which was mainly caused by an increase in patients aged <75 years. 2) In 2012, 64% (896 of 1396) of patients suspected of a pancreatic or periampullary carcinoma was discussed within a MDT meeting which was higher in patients aged <75 years and patients starting treatment with curative intent. 3) In 2012, the recommended 3 weeks between final MDT meeting and start of treatment was met in 39% (141 of 363) of patients which was not influenced by patient and tumor characteristics. CONCLUSION: Compliance to three selected quality indicators in pancreatic cancer care was low in 2012. Areas for improvement were identified. Future compliance will be investigated through structured audit and feedback from the Dutch Pancreatic Cancer Audit. PMID- 26560442 TI - Tremelimumab for the treatment of malignant mesothelioma. AB - INTRODUCTION: Tremelimumab demonstrated therapeutic activity in different malignancies, including malignant pleural mesothelioma (MPM); however, continued research could improve the therapeutic index of this agent. AREAS COVERED: This review describes tremelimumab's clinical efficacy, administration and safety in patients affected with MPM and reports the state of the art clinical trials of tremelimumab. A literature search using the PubMed database was conducted using the search terms tremelimumab, MPM, current therapy, immune checkpoint blockage and cytotoxic T lymphocyte-associated antigen-4. Data was also obtained from meeting abstracts and clinical trial registries. EXPERT OPINION: The use of immunotherapy has been extended from melanoma to thoracic malignancies or lung cancer and MPM. The first clinical trials for MPM with drugs modulating immune checkpoints have been tested or are currently being tested with the first results now under critical consideration. Among these drugs, tremelimumab has been attracting attention as a potential new treatment for MPM. Nevertheless, even though clinical efficacy has been preliminarily demonstrated, the cost/benefit ratio of this drug for this neoplasm is yet to be ascertained. PMID- 26560443 TI - Diastasis of symphysis pubis and labor: Systematic review. AB - Symphysis pubis diastasis (SPD) is an infrequent complication of labor that can impair womens' general health through failure of the passive stability of the pelvic girdle. Although conservative approaches are often used to decrease symptoms and interpubic separation, notably few studies have analyzed the effect of these methods on managing the symptoms of women with SPD. The purpose of this study was to review the available literature on the conservative treatment of SPD during pregnancy and labor. A computer-based search using PubMed, PEDro, and CINAHL was performed up to November 2014. We selected all studies that considered women with SPD during pregnancy or labor and treated them with conservative methods and excluded those that included surgical intervention. Eighteen studies were selected, most of which were case reports. Although the overall results of conservative treatment were unclear because of the type and design of the obtained studies, most of the studies reported bed rest in the lateral decubitus position and a pelvic girdle as basic treatments. Additionally, the few clinical trials reported recommended additional physiotherapy, including strengthening and stabilizing exercises, to reduce SPD symptoms. PMID- 26560444 TI - Patient Safety Reporting: Lessons From the Blind Men and the Elephant. PMID- 26560445 TI - Synthesis of Amorphous Monomeric Glass Mixtures for Organic Electronic Applications. AB - We report a divergent synthetic strategy and novel design concept that exploit molecular mixtures to create amorphous organic charge-transporting glasses. Using Suzuki-Miyaura cross-coupling reactions, we synthesized well-defined molecular mixtures in a single step. These solution-processable materials are noncrystalline and show good thermal and morphological stabilities. Moreover, they have robust hole and electron mobilities, which make them excellent candidate materials for organic light-emitting diodes. Our general strategy enables the facile synthesis of noncrystalline materials with well-controlled electronic properties. PMID- 26560446 TI - Dehydration Pathways of 1-Propanol on HZSM-5 in the Presence and Absence of Water. AB - The Bronsted acid-catalyzed gas-phase dehydration of 1-propanol (0.075-4 kPa) was studied on zeolite H-MFI (Si/Al = 26, containing minimal amounts of extra framework Al moieties) in the absence and presence of co-fed water (0-2.5 kPa) at 413-443 K. It is shown that propene can be formed from monomeric and dimeric adsorbed 1-propanol. The stronger adsorption of 1-propanol relative to water indicates that the reduced dehydration rates in the presence of water are not a consequence of the competitive adsorption between 1-propanol and water. Instead, the deleterious effect is related to the different extents of stabilization of adsorbed intermediates and the relevant elimination/substitution transition states by water. Water stabilizes the adsorbed 1-propanol monomer significantly more than the elimination transition state, leading to a higher activation barrier and a greater entropy gain for the rate-limiting step, which eventually leads to propene. In a similar manner, an excess of 1-propanol stabilizes the adsorbed state of 1-propanol more than the elimination transition state. In comparison with the monomer-mediated pathway, adsorbed dimer and the relevant transition states for propene and ether formation are similarly, while less effectively, stabilized by intrazeolite water molecules. PMID- 26560447 TI - Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling. AB - Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID- 26560448 TI - Evaluation and validation of social and psychological markers in randomised trials of complex interventions in mental health: a methodological research programme. AB - BACKGROUND: The development of the capability and capacity to evaluate the outcomes of trials of complex interventions is a key priority of the National Institute for Health Research (NIHR) and the Medical Research Council (MRC). The evaluation of complex treatment programmes for mental illness (e.g. cognitive behavioural therapy for depression or psychosis) not only is a vital component of this research in its own right but also provides a well-established model for the evaluation of complex interventions in other clinical areas. In the context of efficacy and mechanism evaluation (EME) there is a particular need for robust methods for making valid causal inference in explanatory analyses of the mechanisms of treatment-induced change in clinical outcomes in randomised clinical trials. OBJECTIVES: The key objective was to produce statistical methods to enable trial investigators to make valid causal inferences about the mechanisms of treatment-induced change in these clinical outcomes. The primary objective of this report is to disseminate this methodology, aiming specifically at trial practitioners. METHODS: The three components of the research were (1) the extension of instrumental variable (IV) methods to latent growth curve models and growth mixture models for repeated-measures data; (2) the development of designs and regression methods for parallel trials; and (3) the evaluation of the sensitivity/robustness of findings to the assumptions necessary for model identifiability. We illustrate our methods with applications from psychological and psychosocial intervention trials, keeping the technical details to a minimum, leaving the reporting of the more theoretical and mathematically demanding results for publication in appropriate specialist journals. RESULTS: We show how to estimate treatment effects and introduce methods for EME. We explain the use of IV methods and principal stratification to evaluate the role of putative treatment effect mediators and therapeutic process measures. These results are extended to the analysis of longitudinal data structures. We consider the design of EME trials. We focus on designs to create convincing IVs, bearing in mind assumptions needed to attain model identifiability. A key area of application that has become apparent during this work is the potential role of treatment moderators (predictive markers) in the evaluation of treatment effect mechanisms for personalised therapies (stratified medicine). We consider the role of targeted therapies and multiarm trials and the use of parallel trials to help elucidate the evaluation of mediators working in parallel. CONCLUSIONS: In order to demonstrate both efficacy and mechanism, it is necessary to (1) demonstrate a treatment effect on the primary (clinical) outcome, (2) demonstrate a treatment effect on the putative mediator (mechanism) and (3) demonstrate a causal effect from the mediator to the outcome. Appropriate regression models should be applied for (3) or alternative IV procedures, which account for unmeasured confounding, provided that a valid instrument can be identified. Stratified medicine may provide a setting where such instruments can be designed into the trial. This work could be extended by considering improved trial designs, sample size considerations and measurement properties. FUNDING: The project presents independent research funded under the MRC-NIHR Methodology Research Programme (grant reference G0900678). PMID- 26560449 TI - Dual daclatasvir and sofosbuvir for treatment of genotype 3 chronic hepatitis C virus infection. AB - Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40-50%), while genotype 3 had an intermediate response rate (60-70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3. PMID- 26560450 TI - Nature Index 2015 Collaborations. PMID- 26560451 TI - Strength in numbers. PMID- 26560452 TI - Comment: A well-connected world. PMID- 26560453 TI - Developing partnerships. PMID- 26560454 TI - China's diaspora brings it home. PMID- 26560455 TI - Industrial-strength bonds. PMID- 26560456 TI - Opening borders and barriers. PMID- 26560457 TI - A guide to the Nature Index. PMID- 26560459 TI - Epoch-based Entropy for Early Screening of Alzheimer's Disease. AB - In this paper, we introduce a novel entropy measure, termed epoch-based entropy. This measure quantifies disorder of EEG signals both at the time level and spatial level, using local density estimation by a Hidden Markov Model on inter channel stationary epochs. The investigation is led on a multi-centric EEG database recorded from patients at an early stage of Alzheimer's disease (AD) and age-matched healthy subjects. We investigate the classification performances of this method, its robustness to noise, and its sensitivity to sampling frequency and to variations of hyperparameters. The measure is compared to two alternative complexity measures, Shannon's entropy and correlation dimension. The classification accuracies for the discrimination of AD patients from healthy subjects were estimated using a linear classifier designed on a development dataset, and subsequently tested on an independent test set. Epoch-based entropy reached a classification accuracy of 83% on the test dataset (specificity = 83.3%, sensitivity = 82.3%), outperforming the two other complexity measures. Furthermore, it was shown to be more stable to hyperparameter variations, and less sensitive to noise and sampling frequency disturbances than the other two complexity measures. PMID- 26560460 TI - Spice use in food: Properties and benefits. AB - Spices are parts of plants that due to their properties are used as colorants, preservatives, or medicine. The uses of spices have been known since long time, and the interest in the potential of spices is remarkable due to the chemical compounds contained in spices, such as phenylpropanoids, terpenes, flavonoids, and anthocyanins. Spices, such as cumin (cuminaldehyde), clove (eugenol), and cinnamon (cinnamaldehyde) among others, are known and studied for their antimicrobial and antioxidant properties due to their main chemical compounds. These spices have the potential to be used as preservatives in many foods namely in processed meat to replace chemical preservatives. Main chemical compounds in spices also confer other properties providing a variety of applications to spices, such as insecticidal, medicines, colorants, and natural flavoring. Spices provide beneficial effects, such as antioxidant activity levels that are comparable to regular chemical antioxidants used so they can be used as a natural alternative to synthetic preservatives. In this review, the main characteristics of spices will be described as well as their chemical properties, different applications of these spices, and the advantages and disadvantages of their use. PMID- 26560461 TI - Effectiveness and Usability of Bioinformatics Tools to Analyze Pathways Associated with miRNA Expression. AB - MiRNAs are small, nonprotein-coding RNA molecules involved in gene regulation. While bioinformatics help guide miRNA research, it is less clear how they perform when studying biological pathways. We used 13 criteria to evaluate effectiveness and usability of existing bioinformatics tools. We evaluated the performance of six bioinformatics tools with a cluster of 12 differentially expressed miRNAs in colorectal tumors and three additional sets of 12 miRNAs that are not part of a known cluster. MiRPath performed the best of all the tools in linking miRNAs, with 92% of all miRNAs linked as well as the highest based on our established criteria followed by Ingenuity (58% linked). Other tools, including Empirical Gene Ontology, miRo, miRMaid, and PhenomiR, were limited by their lack of available tutorials, lack of flexibility and interpretability, and/or difficulty using the tool. In summary, we observed a lack of standardization across bioinformatic tools and a general lack of specificity in terms of pathways identified between groups of miRNAs. Hopefully, this evaluation will help guide the development of new tools. PMID- 26560462 TI - Control of vein network topology by auxin transport. AB - BACKGROUND: Tissue networks such as the vascular networks of plant and animal organs transport signals and nutrients in most multicellular organisms. The transport function of tissue networks depends on topological features such as the number of networks' components and the components' connectedness; yet what controls tissue network topology is largely unknown, partly because of the difficulties in quantifying the effects of genes on tissue network topology. We address this problem for the vein networks of plant leaves by introducing biologically motivated descriptors of vein network topology; we combine these descriptors with cellular imaging and molecular genetic analysis; and we apply this combination of approaches to leaves of Arabidopsis thaliana that lack function of, overexpress or misexpress combinations of four PIN-FORMED (PIN) genes--PIN1, PIN5, PIN6, and PIN8--which encode transporters of the plant signal auxin and are known to control vein network geometry. RESULTS: We find that PIN1 inhibits vein formation and connection, and that PIN6 acts redundantly to PIN1 in these processes; however, the functions of PIN6 in vein formation are nonhomologous to those of PIN1, while the functions of PIN6 in vein connection are homologous to those of PIN1. We further find that PIN8 provides functions redundant and homologous to those of PIN6 in PIN1-dependent inhibition of vein formation, but that PIN8 has no functions in PIN1/PIN6-dependent inhibition of vein connection. Finally, we find that PIN5 promotes vein formation; that all the vein-formation-promoting functions of PIN5 are redundantly inhibited by PIN6 and PIN8; and that these functions of PIN5, PIN6, and PIN8 are independent of PIN1. CONCLUSIONS: Our results suggest that PIN-mediated auxin transport controls the formation of veins and their connection into networks. PMID- 26560463 TI - Afferent and efferent connections of C1 cells with spinal cord or hypothalamic projections in mice. AB - The axonal projections and synaptic input of the C1 adrenergic neurons of the rostral ventrolateral medulla (VLM) were examined using transgenic dopamine-beta hydroxylase Cre mice and modified rabies virus. Cre-dependent viral vectors expressing TVA (receptor for envelopeA) and rabies glycoprotein were injected into the left VLM. EnvelopeA-pseudotyped rabies-EGFP glycoprotein-deficient virus (rabies-EGFP) was injected 4-6 weeks later in either thoracic spinal cord (SC) or hypothalamus. TVA immunoreactivity was detected almost exclusively (95 %) in VLM C1 neurons. In mice with SC injections of rabies-EGFP, starter cells (expressing TVA + EGFP) were found at the rostral end of the VLM; in mice with hypothalamic injections starter C1 cells were located more caudally. C1 neurons innervating SC or hypothalamus had other terminal fields in common (e.g., dorsal vagal complex, locus coeruleus, raphe pallidus and periaqueductal gray matter). Putative inputs to C1 cells with SC or hypothalamic projections originated from the same brain regions, especially the lower brainstem reticular core from spinomedullary border to rostral pons. Putative input neurons to C1 cells were also observed in the nucleus of the solitary tract, caudal VLM, caudal spinal trigeminal nucleus, cerebellum, periaqueductal gray matter and inferior and superior colliculi. In sum, regardless of whether they innervate SC or hypothalamus, VLM C1 neurons receive input from the same general brain regions. One interpretation is that many types of somatic or internal stimuli recruit these neurons en bloc to produce a stereotyped acute stress response with sympathetic, parasympathetic, vigilance and neuroendocrine components. PMID- 26560465 TI - [Not Available]. PMID- 26560464 TI - Effects of Seasonal Upwelling on Inorganic and Organic Matter Dynamics in the Water Column of Eastern Pacific Coral Reefs. AB - The Gulf of Papagayo at the northern Pacific coast of Costa Rica experiences pronounced seasonal changes in water parameters caused by wind-driven coastal upwelling. While remote sensing and open water sampling already described the physical nature of this upwelling, the spatial and temporal effects on key parameters and processes in the water column have not been investigated yet, although being highly relevant for coral reef functioning. The present study investigated a range of water parameters on two coral reefs with different exposure to upwelling (Matapalo and Bajo Rojo) in a weekly to monthly resolution over one year (May 2013 to April 2014). Based on air temperature, wind speed and water temperature, three time clusters were defined: a) May to November 2013 without upwelling, b) December 2013 to April 2014 with moderate upwelling, punctuated by c) extreme upwelling events in February, March and April 2014. During upwelling peaks, water temperatures decreased by 7 degrees C (Matapalo) and 9 degrees C (Bajo Rojo) to minima of 20.1 and 15.3 degrees C respectively, while phosphate, ammonia and nitrate concentrations increased 3 to 15-fold to maxima of 1.3 MUmol PO43- L-1, 3.0 MUmol NH4+ L-1 and 9.7 MUmol NO3- L-1. This increased availability of nutrients triggered several successive phytoplankton blooms as indicated by 3- (Matapalo) and 6-fold (Bajo Rojo) increases in chlorophyll a concentrations. Particulate organic carbon and nitrogen (POC and PON) increased by 40 and 70% respectively from February to April 2014. Dissolved organic carbon (DOC) increased by 70% in December and stayed elevated for at least 4 months, indicating high organic matter release by primary producers. Such strong cascading effects of upwelling on organic matter dynamics on coral reefs have not been reported previously, although likely impacting many reefs in comparable upwelling systems. PMID- 26560466 TI - [Quality management and quality assurance]. PMID- 26560467 TI - [In Process Citation]. PMID- 26560468 TI - CORR Insights((r)): Obesity is Not Associated with Increased Short-term Complications After Primary Total Shoulder Arthroplasty. PMID- 26560469 TI - Help-Seeking Behavior for Children with Acute Respiratory Infection in Ethiopia: Results from 2011 Ethiopia Demographic and Health Survey. AB - BACKGROUND: Acute respiratory infection is a major contributor to morbidity and mortality among children under five years of age in Ethiopia. While facilities have been implemented to address this problem they are underused due to a lack in help-seeking behavior. This study investigates factors related to the help seeking behavior of mothers for children with acute respiratory infection using data from the 2011 Ethiopia Demographic and Health Survey. METHODS: Data on 11,030 children aged 0-59 months obtained through interviewing women aged 15-49 years throughout Ethiopia was available. Descriptive statistics and logistic regression analyses were performed to determine which factors are related to help seeking behavior for acute respiratory infection. RESULTS: In the two weeks prior to the survey, 773(7%) of the children were reported to have symptoms of acute respiratory infection while treatment was sought for only 209 (27.2%). The odds ratio for acute respiratory infection was 1.6 (95% CI: 1.2-2.0) for rural residence with only 25.2% of these mothers seeking help compared to 46.4% for mothers with an urban residence. Smaller family size, younger mothers' age and having had prenatal care had a statistically significant odds ratio greater than 1 for both urban and rural residences. Highest wealth index had a statistically significant odds ratio greater than 1 for rural residence only, whereas primary education or higher had a statistically significant odds ratio greater than 1 for urban residence. CONCLUSIONS: Children from rural areas are more at risk for acute respiratory infection while their mothers are less likely to seek help. Nevertheless, there is also underuse of available services in urban areas. Interventions should target mothers with less education and wealth and older mothers. Expanding prenatal care among these groups would encourage a better use of available facilities and subsequently better care for their children. PMID- 26560470 TI - Abolishing the internal market to save NHS costs. PMID- 26560471 TI - Efficacy and safety of botulinum toxin injection for benign prostatic hyperplasia: a systematic review and meta-analysis. AB - PURPOSE: The aim of this study was to overcome the limitation of overlooking the placebo effect in previous studies and to demonstrate the overall treatment efficacy and safety of botulinum toxin type A (BTX-A) compared with placebo. METHODS: We conducted a systematic review and meta-analysis of the published literature in PubMed, Cochrane Library, and Embase reporting on BTX use in lower urinary tract symptoms (LUTS)/benign prostate hyperplasia (BPH). Single-group analysis for the placebo effect and meta-regression analysis for the moderator effect were performed with high-quality RCTs compared with placebo. RESULTS: A total of three studies were included, with a total sample size of 522 subjects (260 subjects in the experimental group and 262 subjects in the control group). Study duration ranged from 8 to 24 weeks. The pooled overall SMD in the mean change in IPSS for the BTX-A group versus the placebo group was -1.02 (95 % CI 1.97, -0.07). The other outcomes (Q max, prostate volume, and post-voided residual volume) were not statistically different between the two groups. The placebo effect in single-group analysis ranged from 0 to 27.9 % for IPSS, and from -1.1 to 28.7 % for Q max (lowest to highest, respectively). CONCLUSIONS: This evidence-based systematic review and meta-analysis of the BTX-A injection for LUTS/BPH showed no differences in efficacy compared with placebo and also showed no difference in procedure-related adverse events occurred. Thus, the results of this study do not provide evidence of clinical benefits of using the BTX-A injection for LUTS/BPH in real clinical practice. PMID- 26560472 TI - Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)/P glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis. AB - OBJECTIVES: We investigated the possible involvement of multidrug resistance protein 1 P-glycoprotein (MDR1 P-gp) in the oxalate-induced redistribution of phosphatidylserine in renal epithelial cell membranes. METHODS: Real-time PCR and western blotting were used to examine MDR1 expression in Madin-Darby canine kidney cells at the mRNA and protein levels, respectively, whereas surface expressed phosphatidylserine was detected by the annexin V-binding assay. RESULTS: Oxalate treatment resulted in increased synthesis of MDR1, which resulted in phosphatidylserine (PS) externalization in the renal epithelial cell membrane. Treatment with the MDR1 inhibitor PSC833 significantly attenuated phosphatidylserine externalization. Transfection of the human MDR1 gene into renal epithelial cells significantly increased PS externalization. CONCLUSIONS: To our knowledge, this study is the first to show that oxalate increases the synthesis of MDR1 P-gp, which plays a key role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells. PMID- 26560473 TI - A comparison of RIFLE, AKIN, KDIGO, and Cys-C criteria for the definition of acute kidney injury in critically ill patients. AB - PURPOSE: AKI is a major clinical problem and predictor of prognosis in critically ill patients. The aim of our study was to determine whether the new Cys-C criteria for identification and prognosis of AKI were superior to the RIFLE, AKIN, and KDIGO criteria. METHODS: In the retrospective and multicenter study, the incidence of AKI was identified by the four criteria. Receiver operating characteristic (ROC) curve was applied to compare the predictive ability for 28 day mortality, and logistic regression analysis was used for the calculation of odds ratios and 95 % confidence intervals. RESULTS: In the 1036 patients enrolled, the incidences of AKI were 26.4, 34.1, 37.8, and 36.1 %, respectively, under the four criteria. Patients with AKI had higher mortality and longer length of stay than those without in all definitions. Concordance in AKI diagnosis between Cys-C and KDIGO criteria was 95.9 %, higher than AKIN and RIFLE criteria (p < 0.0001). The area under ROC curves was 0.7023 for Cys-C criteria, which was a significantly greater discrimination (p < 0.05). CONCLUSION: KDIGO criteria identified significantly more AKI and AKI patients had significantly higher 28 day mortality than patients without AKI. The Cys-C criteria were more predictive for short-term outcomes than other three criteria among critically ill patients. PMID- 26560474 TI - Lateroconal fascia suspension for management of peritoneal tear and "curtain" effect during retroperitoneal laparoscopic operations. AB - PURPOSE: To describe the method of lateroconal fascia suspension for the management of peritoneal tear and curtain effect during retroperitoneal laparoscopic operations. MATERIALS AND METHODS: Between May 2013 and October 2014, we performed lateroconal fascia suspension in 30 cases of retroperitoneal laparoscopic operations. Peritoneal tear occurred and retroperitoneal space collapsed in 18 cases of them during the operation, and free edge of the lateroconal fascia caused curtain effect and sheltered the field of view in another 12 cases after the lateroconal fascia was incised longitudinally. RESULTS: The curtain effect of lateroconal fascia was eliminated successfully, and the sheltered field of view got normal in all the 12 cases. The collapsed retroperitoneal space due to peritoneal tear got enlarged effectively and was sufficient for the following operations in 15 patients of the overall 18 cases, while the collapsed retroperitoneal space did not get enlarged significantly in the other three cases. After the insertion of an extra 5-mm trocar into peritoneal space, the collapsed retroperitoneal space got enlarged eventually. Finally, retroperitoneal laparoscopic operations were continued and completed successfully in all these 30 patients. It took 4 min to complete the suspension procedure, and no related complications occurred during the whole suspension process. CONCLUSION: Lateroconal fascia suspension method could manage most peritoneal tears and curtain effect effectively during retroperitoneal laparoscopic operations. PMID- 26560475 TI - Urinary microprotein concentrations in the long-term follow-up of dilating vesicoureteral reflux patients who underwent medical or surgical treatment. AB - PURPOSE: This study examined the relationship between urinary microprotein concentrations and renal functional parameters in children with dilating (grade III-V) vesicoureteral reflux (VUR) who underwent either medical or surgical treatment. METHODS: All 44 dilating VUR patients who were followed for 4 years were screened for inclusion in this study. The patients' clinical features and clinical outcomes, as well as the urinary activities of albumin (ALB), transferrin (TRF), immunoglobulin G (IgG), alpha-1-microglobulin (alpha1-MG), and N-acetyl-beta-glucosaminidase (NAG), were retrospectively analyzed. RESULTS: High values of NAG, alpha1-MG, IgG, TRF, and ALB were noted in 73.33, 58.33, 43.33, 24.14, and 53.33 % of patients, respectively, at the first examination. Cystatin C, eGFR, and urinary microprotein levels were associated with a good prognosis after 4 years of follow-up. No differences in recurrent UTI, cystatin C concentration, most microprotein/creatinine (Cr) ratios, eGFR, or DeltaGFR4 % were found between the groups. High levels of urinary proteins were found in 2.38 9.52 % of cases after 4 years of follow-up. ALB/Cr, IgG/Cr, and alpha1-MG/Cr levels were positively correlated with 99mTc-dimercaptosuccinic acid (DMSA) grade, and alpha1-MG excretion was inversely correlated with eGFR. CONCLUSIONS: The levels of microprotein were elevated at diagnosis in a higher proportion of patients than for the other markers examined. At long-term follow-up, the reflux level had decreased or completely resolved in all patients, and the proportions of microproteins that were elevated were significantly reduced. Renal impairment measured by eGFR and DMSA grade was related to increased urinary alpha1-MG levels. PMID- 26560476 TI - Impact of dialysis modality on the survival of patients with end-stage renal disease and prior stroke. AB - PURPOSE: Of patients with end-stage renal disease (ESRD), 8-16 % had a history of stroke at dialysis initiation. We used the National Health Insurance Research Database of Taiwan to evaluate whether peritoneal dialysis (PD) or hemodialysis (HD) confers a survival advantage for patients with incident ESRD and prior stroke. METHODS: We identified 975 patients undergoing PD and 975 propensity score-matched patients with newly diagnosed ESRD and prior stroke undergoing HD between 2000 and 2010. Both cohorts were followed up until the end of 2011. Comparisons of the risks of mortality between PD and HD were analyzed using the Cox proportional hazards regression model. RESULTS: In the propensity score matched cohorts, there was a 2.4 per 100 person-years greater mortality in patients with PD (20.4 vs. 18.0 per 100 person-years) with an adjusted hazard ratio (HR) of 1.20 (95 % CI 1.06-1.36). For patients with diabetes, ESRD and prior stroke, patients undergoing PD had inferior survival compared with those undergoing HD (adjusted HR 1.22, 95 % CI 1.05-1.43), particularly among female patients (adjusted HR 1.55, 95 % CI 1.25-1.91). For patients with ESRD and prior stroke but without diabetes, there was no significant difference in mortality between PD and HD (adjusted HR 1.20, 95 % CI 0.96-1.50). CONCLUSIONS: PD was associated with overall poorer survival among patients with diabetes, ESRD and prior stroke and with similar overall survival among patients with ESRD and prior stroke, but without diabetes, compared with HD. PMID- 26560477 TI - Hemodiafiltration and hemodialysis differently affect P wave duration and dispersion on the surface electrocardiogram. AB - AIM: The incidence of atrial fibrillation is increased during hemodialysis (HD); however, the effects of hemodiafiltration (HDF) on atrial arrhythmias have not been evaluated. The prolongation of the P wave and P dispersion (Pd) can predict atrial arrhythmias. METHODS: Data from 30 patients receiving HDF over a period of 3 months were collected; the same group of patients was then evaluated during treatment with conventional HD for at least another 3 months. Electrolyte values were obtained, and surface electrocardiograms (ECG), echocardiography, and Holter ECGs were performed. RESULTS: The duration of the P wave and Pd increased significantly during HD. The left atrial diameter decreased significantly only during HDF. During HDF, the left atrial cross diameter measured at the beginning of the session was positively correlated with the incidence of supraventricular premature beats (p = 0.011, r = 0.4556). The decrease in left atrial diameter during HDF was negatively correlated with the incidence of supraventricular premature beats (p = 0.016, r = -0.43). During HDF, the changes in sodium and Pd were significantly positively correlated (p < 0.05, r = 0.478). During HD, the changes in ionized calcium levels and Pd were positively correlated (p < 0.05, r = 0.377). CONCLUSION: Our results suggest that HDF has a more beneficial effect on P wave duration and Pd than HD. The alterations in the ECG markers may be the result of the simultaneous occurrence of certain electrolyte imbalances and renal replacement methods. PMID- 26560478 TI - Iroquois homeobox 2 suppresses cellular motility and chemokine expression in breast cancer cells. AB - BACKGROUND: Disseminated tumor cells (DTCs) can be detected using ultrasensitive immunocytochemical assays and their presence in the bone marrow can predict the subsequent occurrence of overt metastasis formation and metastatic relapse. Using expression profiling on early stage primary breast tumors, low IRX2 expression was previously shown to be associated with the presence of DTCs in the bone marrow, suggesting a possible role of IRX2 in the early steps of metastasis formation. The purpose of this study is to gain insights into the significance of IRX2 protein function in the progression of breast cancer. METHODS: To assess the physiological relevance of IRX2 in breast cancer, we evaluated IRX2 expression in a large breast cancer cohort (n = 1992). Additionally, constitutive IRX2 over expression was established in BT-549 and Hs578T breast cancer cell lines. Subsequently we analyzed whether IRX2 overexpression effects chemokine secretion and cellular motility of these cells. RESULTS: Low IRX2 mRNA expression was found to correlate with high tumor grade, positive lymph node status, negative hormone receptor status, and basal type of primary breast tumors. Also in cell lines low IRX2 expression was associated with mainly basal breast cancer cell lines. The functional studies show that overexpression of the IRX2 transcription factor in basal cell lines suppressed secretion of the pro-metastatic chemokines and inhibited cellular motility but did not influence cell proliferation. CONCLUSION: Our results imply that the IRX2 transcription factor might represent a novel metastasis associated protein that acts as a negative regulator of cellular motility and as a repressor of chemokine expression. Loss of IRX2 expression could therefore contribute to early hematogenous dissemination of breast cancer by sustaining chemokine secretion and enabling mobilization of tumor cells. PMID- 26560479 TI - The antiradical activity of some selected flavones and flavonols. Experimental and quantum mechanical study. AB - The aim of the study was to examine the antiradical and antioxidant activity of some flavones and flavonols with different models of hydroxylation and methoxylation. Antiradical activity was measured using ABTS and DPPH radicals and ferric ions (FRAP test). The reduction potential of the compounds was also investigated by determination of minimal hydrogen abstraction energy for each of the hydroxyl hydrogens of all compounds using quantum chemistry methods. Quercetin appeared to be a strong antioxidant when the FRAP test was performed and the strongest for ABTS and DPPH tests whereas genkwanin was the weakest antioxidant for three tests (FRAP, ABTS, and DPPH). Flavonols appeared to have much stronger antiradical activity than flavones. An exception was luteolin, which belongs to flavones but exhibited antiradical activity comparable to that of flavonols, probably due to the presence of a hydroxyl group in the B ring at the 3' position next to another hydroxyl group at position 4'. The study using UB3LYP/6-31G(d,p) model chemistry of density functional theory (DFT) showed the lowest hydrogen abstraction energy (HAE) for the hydroxyl group situated at 3' or 5' of myricetin. Based on the experimental results and computational studies, we conclude that the hydroxyl group situated at 4' in the B ring in flavonoids, and to a lesser at the 3' and 3 position in flavonols is the most important for antioxidant activity of flavonoids. We observe strong negative Spearman's rank order correlations between minimal HAE and antiradical activity of flavonoids in all three tests and double-tailed rejection P values are less than 0.001. PMID- 26560480 TI - An investigation of folic acid-protein association sites and the effect of this association on folic acid self-assembly. AB - The contribution of folic acid (FA)-tryptophan interactions to FA-protein association was investigated in the context of using FA as a drug carrier in protein delivery systems. Bovine serum albumin (BSA) and indolicidin were used as model proteins in the study. The FA-BSA complex was characterized by using the Bradford reagent to identify the impact of FA-BSA association on BSA-dye reagent interactions. UV-visible spectroscopic analysis of the FA-BSA mixture showed that the absorbance maximum of BSA-dye reagent occurred at 595 nm, even after the association of FA with BSA. This confirms that protonated amino acid groups of the protein are not involved in FA-BSA association. Moreover, molecular dynamics (MD) simulation confirmed the presence of an associative interaction between aromatic moieties in FA and tryptophan moieties in the indolicidin molecule, which disrupted FA self-assembly. An X-ray diffraction (XRD) study showed that there was limited disruption of FA self-assembly after the addition of BSA or tryptophan. This suggests that FA and BSA are compatible and associate with each other. Graphical Abstract Mechanism of folic acid and protein association. PMID- 26560481 TI - Added Sugar, Macro- and Micronutrient Intakes and Anthropometry of Children in a Developing World Context. AB - OBJECTIVE: The objective of this study was to determine the relationship between added sugar and dietary diversity, micronutrient intakes and anthropometric status in a nationally representative study of children, 1-8.9 years of age in South Africa. METHODS: Secondary analysis of a national survey of children (weighted n = 2,200; non weighted n = 2818) was undertaken. Validated 24-hour recalls of children were collected from mothers/caregivers and stratified into quartiles of percentage energy from added sugar (% EAS). A dietary diversity score (DDS) using 9 food groups, a food variety score (FVS) of individual food items, and a mean adequacy ratio (MAR) based on 11 micronutrients were calculated. The prevalence of stunting and overweight/obesity was also determined. RESULTS: Added sugar intake varied from 7.5-10.3% of energy intake for rural and urban areas, respectively. Mean added sugar intake ranged from 1.0% of energy intake in Quartile 1 (1-3 years) (Q1) to 19.3% in Q4 (4-8 years). Main sources of added sugar were white sugar (60.1%), cool drinks (squash type) (10.4%) and carbonated cool drinks (6.0%). Added sugar intake, correlated positively with most micronutrient intakes, DDS, FVS, and MAR. Significant negative partial correlations, adjusted for energy intake, were found between added sugar intake and intakes of protein, fibre, thiamin, pantothenic acid, biotin, vitamin E, calcium (1-3 years), phosphorus, iron (4-8 years), magnesium and zinc. The prevalence of overweight/obesity was higher in children aged 4-8 years in Q4 of %EAS than in other quartiles [mean (95%CI) % prevalence overweight 23.0 (16.2-29.8)% in Q4 compared to 13.0 (8.7-17.3)% in Q1, p = 0.0063]. CONCLUSION: Although DDS, FVS, MAR and micronutrient intakes were positively correlated with added sugar intakes, overall negative associations between micronutrients and added sugar intakes, adjusted for dietary energy, indicate micronutrient dilution. Overweight/obesity was increased with higher added sugar intakes in the 4-8 year old children. PMID- 26560482 TI - Molecular signatures of mesenchymal stem cell-derived extracellular vesicle mediated tissue repair. AB - Extracellular vesicles (EVs) play important roles in intercellular communications via their content molecules, and mimic, at least in part, the roles that are played by their originating cells. Consistent with this notion, an increasing number of reports have suggested that EVs derived from mesenchymal stem cells (MSCs), which are therapeutically beneficial to a wide range of diseases, can serve as drugs to treat multiple diseases. EVs contain a variety of molecules, including proteins, microRNAs, and mRNAs, and are associated with biological processes in a content molecule-dependent manner. In this article, we review the latest reports regarding the therapeutic potential of MSC-EVs by focusing on the underlying molecular mechanisms of their effects. Specifically, we feature the effects of MSC-EVs in terms of their content molecules and of the tissue recovery processes endowed by these molecules. PMID- 26560484 TI - Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer. AB - PURPOSE: We conducted a retrospective cohort study to examine whether neutropenia could be an indicator of good prognosis in patients treated with gemcitabine (GEM) for unresectable pancreatic cancer. METHODS: A total of 178 patients with unresectable pancreatic cancer, who were treated with first-line (n = 121) or second-line (n = 57) GEM, were included in our analyses. A Cox proportional hazard model was used to examine the effect of the grade of GEM-induced neutropenia on prognosis. Furthermore, the difference in survival time for each grade was assessed using a log-rank test. RESULTS: In the first-line population, the hazard ratios of patients with grade 2 or grade 3 neutropenia compared with the ratios of those without neutropenia (grade 0) were 0.43 (95% CI 0.27-0.70) and 0.37 (0.21-0.65), respectively (p < 0.05). The median survival time (MST) was 3.8 months for grade 0, 9.4 months for grade 2, and 10.1 for grade 3. Landmark analysis of the second-line population revealed a hazard ratio of 0.52 (0.30 0.82) for grade 1 and 0.49 for grade 2 (0.28-0.72) (p < 0.05). MST was 1.3 months for grade 0, 4.7 months for grade 1, and 4.6 months for grade 2. CONCLUSIONS: We found that neutropenia grade was an indicator of good prognosis in patients treated with first-line and second-line GEM for unresectable pancreatic cancer. A prospective study should be performed to examine whether dosage adjustment using neutropenia grade as an indicator would improve prognosis. PMID- 26560483 TI - Effect of pH adjustment by mixing steroid for venous pain in colorectal cancer patients receiving oxaliplatin through peripheral vein: a multicenter randomized phase II study (APOLLO). AB - PURPOSE: The aim of this phase II clinical trial was to evaluate the preventive effect of dexamethasone mixing injection for venous pain in patients with colorectal cancer during chemotherapy. MATERIALS AND METHODS: Patients were randomized to receive a 2-h intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 followed by capecitabine 1000 mg/m(2) (or S-1 40-60 mg/m(2)) twice daily on days 1 through 14 of every 3 weeks with or without dexamethasone 1.65 mg at the infusion on day 1. RESULTS: A total of 53 patients were enrolled. The analysis population consisted of 49 patients (arm A, with dexamethasone N = 24; arm B, without dexamethasone N = 25). The incidence of venous pain >=grade 2 based on the CTCAE version 4.0 was 33.3 % in arm A and 56.0 % in arm B (relative risk 0.60; 95 % CI 0.31-1.16). The incidences based on the verbal rating scale for arms A and B were 50.0 and 64.0 %, respectively (relative risk 0.78; 95 % CI 0.48 1.28). CONCLUSION: The primary endpoint was not met in this preliminary study. PMID- 26560485 TI - Schedule-dependent modulation of the pharmacokinetics of MK-2206, an oral pan-AKT inhibitor: perspectives. PMID- 26560486 TI - Phase I study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer. AB - PURPOSE: This open-label, phase I, dose-escalation part of a phase I/II study evaluated the safety, pharmacokinetics, and preliminary efficacy of nintedanib, a triple angiokinase inhibitor, combined with pemetrexed in Japanese patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. METHODS: A fixed dose of pemetrexed (500 mg/m(2) iv) was administered on Day 1 of each 21-day cycle followed by oral nintedanib twice daily (bid) on days 2-21, starting at 100 mg bid and escalating to 200 mg bid in 50-mg intervals, using a standard 3 + 3 design. After >=4 cycles of combination therapy, patients could continue nintedanib monotherapy until disease progression or undue adverse events (AEs). Primary endpoints were maximum tolerated dose (MTD), defined as the highest dose at which the incidence of dose-limiting toxicities (DLTs) was <33.3 % during the first treatment course, and AEs (CTCAE v3.0). DLTs were primarily defined as grade >=3 non-hematologic or grade 4 hematologic AEs. RESULTS: Eighteen patients were included in the analysis. DLTs were experienced by 2/9 patients receiving 200 mg bid, 1/6 receiving 150 mg bid, and 0/3 receiving the lowest dose. The MTD of nintedanib plus pemetrexed was 200 mg bid. The most common drug-related AEs were elevated liver enzymes and gastrointestinal AEs. Two patients achieved partial response, and 10 had stable disease. CONCLUSIONS: Nintedanib plus pemetrexed had a manageable safety profile and showed promising signs of efficacy in previously treated Japanese patients with advanced NSCLC. As in Caucasian patients, the MTD of nintedanib was 200 mg bid. Clinical trial information NCT00979576. PMID- 26560487 TI - Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation. AB - PURPOSE: Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non steroidal drugs. METHODS: Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. RESULTS: Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. CONCLUSIONS: These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery. PMID- 26560488 TI - Biochemical markers of placental dysfunction in assisted conception. AB - A possible mechanism for poor perinatal outcomes in singleton pregnancies conceived following assisted reproductive technologies (ART) and those conceived naturally following a period of infertility (>12 months) is thought to be placental dysfunction. This was investigated by measuring plasma concentrations of biochemical markers: (i) soluble fms-like tyrosine kinase1 (sFlt1); (ii) placental growth factor (PlGF); (iii) leptin; and (iv) plasminogen activator inhibitor 2 (PAI-2), serially at four antenatal time points. Baseline concentrations of each marker after delivery were also measured. The control group was naturally conceived singleton pregnancies with no history of infertility. Non-smoking, age-matched nulliparous women with no significant medical history were recruited to all groups. The ART group had significantly lower mean plasma concentrations of PlGF at all antenatal time points compared to the control group (p < 0.001). The subfertility (SF) group had significantly higher mean serum concentrations of leptin than the other groups at all time points (p < 0.001), even after correction for body mass index. There were no significant differences in sFlt1 and PAI-2 concentrations between the groups. Low plasma PlGF concentrations in the ART group might suggest abnormal placentation and/or abnormal function in ART pregnancies with relevance to pathogenesis of pregnancy complications in these women. PMID- 26560489 TI - Targeting angiogenesis in endometrial cancer - new agents for tailored treatments. AB - INTRODUCTION: Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries. The majority of women presents with low-grade tumors but a significant subset of women experience recurrence and do not survive their disease. Patients with stage III/ IV or recurrent endometrial cancer have a poor prognosis. Identification of active and tolerable new targeted agents versus specific molecular targets is a priority objective. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer and in particular endometrial cancer. AREAS COVERED: In this review, the authors highlight the main angiogenetic molecular pathways and the anti-angiogenic agents in Phase II clinical trials for endometrial cancer treatment. The authors focus on reports from recent years on angiogenesis inhibitors used in endometrial cancer, including anti- vascular endothelial growth factor (VEGF) monoclonal antibodies (bevacizumab and aflibercept), mammalian target of rapamycin inhibitors (mTORi) (everolimus, temsirolimus and ridaforolimus), PI3 K inhibitors (BKM120), tyrosine kinase inhibitors (brivanib, sunitinib, dovitinib and nintedanib) and thalidomide. EXPERT OPINION: These anti-angiogenic drugs, while used either alone or in combination with chemotherapy, have presented mixed results in treating endometrial cancer patients. Challenges for the future include the identification of new pathways, early identification and overcoming resistance and the use of these molecules in combination with old and new chemotherapeutic and targeted agents. PMID- 26560491 TI - Reassessing the boundaries of liver transplantation for hepatocellular carcinoma: Where do we stand with tumor down-staging? AB - Down-staging of hepatocellular carcinoma prior to liver transplantation (LT) has generated a lot of interest in recent years and has been identified in two recent national conferences on hepatocellular carcinoma as one of the priorities for research. Down-staging is defined as reduction in the tumor burden using local regional therapy specifically to meet acceptable criteria for LT. The rationale behind down-staging of tumors initially exceeding conventional criteria for LT is to select a subgroup of tumors with favorable biology and prognosis for LT as assessed by their response to local regional therapy. The expectation is to achieve comparable posttransplant survival between patients who achieve successful tumor down-staging before LT and those whose tumors meet LT criteria at the outset without needing down-staging. The application of tumor down-staging requires a highly structured approach using a treatment protocol that includes five essential components: eligibility criteria, down-staging endpoints, selection of the type of local regional therapy, minimal observation period from successful tumor down-staging to LT, and criteria for treatment failure and exclusion from LT. This review article summarizes published data on down-staging and addresses key questions related to each of the components of the down-staging protocol as well as treatment efficacy. CONCLUSION: Based on a review of published data and recommendations from recent national and international conferences on hepatocellular carcinoma and LT, a standardized down-staging protocol is proposed to further evaluate the feasibility and efficacy of applying tumor down-staging on a broader scale. PMID- 26560492 TI - A Case of Hepatotoxicity Induced by Adulterated "Tiger King", a Chinese Herbal Medicine Containing Sildenafil. AB - Detection of Phosphodiesterase Type 5 (PDE-5) inhibitors and their analogues in "100% natural" or "herbal" supplements have been described in numerous reports. However, few reports have been published in relation to actual harm caused by counterfeit erectile dysfunction herbal supplements. We describe a case of a 65 year old male admitted to a tertiary hospital with acute liver toxicity, possibly induced by adulterated "Chinese herbal" supplement "Tiger King" for sexual enhancement. Chemical analysis of the tablets discovered the presence of therapeutic doses of sildenafil with no other herbal components. Other medications were excluded as potential causes of the hepatic impairment. According to the Naranjo adverse drug reaction scale and the Roussel Uclaf Causality Assessment Method (RUCAM) the probability of association of Hepatotoxicity with Sildenafil was "possible" and "probable" respectively (Naranjo score of 4, RUCAM score of 7). Within three days of admission, the patient's clinical status and liver function improved without any specific treatment. His liver function tests normalized 30 days post discharge. Further pharmacovigilance actions should be taken by regulatory authorities and pharmaceutical companies in order to determine the relation between sildenafil and hepatotoxicity. This case emphasizes the importance of raising public awareness on the potential dangers of "Tiger king" in particular, and other counterfeit medications or herbal supplements of unknown origin. PMID- 26560490 TI - Therapeutic Antiviral Effect of the Nucleic Acid Polymer REP 2055 against Persistent Duck Hepatitis B Virus Infection. AB - Previous studies have demonstrated that nucleic acid polymers (NAPs) have both entry and post-entry inhibitory activity against duck hepatitis B virus (DHBV) infection. The inhibitory activity exhibited by NAPs prevented DHBV infection of primary duck hepatocytes in vitro and protected ducks from DHBV infection in vivo and did not result from direct activation of the immune response. In the current study treatment of primary human hepatocytes with NAP REP 2055 did not induce expression of the TNF, IL6, IL10, IFNA4 or IFNB1 genes, confirming the lack of direct immunostimulation by REP 2055. Ducks with persistent DHBV infection were treated with NAP 2055 to determine if the post-entry inhibitory activity exhibited by NAPs could provide a therapeutic effect against established DHBV infection in vivo. In all REP 2055-treated ducks, 28 days of treatment lead to initial rapid reductions in serum DHBsAg and DHBV DNA and increases in anti-DHBs antibodies. After treatment, 6/11 ducks experienced a sustained virologic response: DHBsAg and DHBV DNA remained at low or undetectable levels in the serum and no DHBsAg or DHBV core antigen positive hepatocytes and only trace amounts of DHBV total and covalently closed circular DNA (cccDNA) were detected in the liver at 9 or 16 weeks of follow-up. In the remaining 5/11 REP 2055-treated ducks, all markers of DHBV infection rapidly rebounded after treatment withdrawal: At 9 and 16 weeks of follow-up, levels of DHBsAg and DHBcAg and DHBV total and cccDNA in the liver had rebounded and matched levels observed in the control ducks treated with normal saline which remained persistently infected with DHBV. These data demonstrate that treatment with the NAP REP 2055 can lead to sustained control of persistent DHBV infection. These effects may be related to the unique ability of REP 2055 to block release of DHBsAg from infected hepatocytes. PMID- 26560493 TI - Eltrombopag Induced Thrombosis: A Case with Acute Myocardial Infarction. AB - Eltrombopag is a non-peptide thrombopoietin receptor agonist. Eltrombopag has originally been developed for conditions where therapy for thrombocytopenia is needed. Secondary to eltrombopag have been reported thrombotic events, chest pain, acute renal failure, neutropenia, ascites, retinal exudates, antiphospholipid syndrome. In this case, we present a 53 year-old patient who had diagnosis of Idiopathic Thrombocytopenic Purpura (ITP) for 30 years with splenectomy. He's still having low thrombocyte counts despite the classical ITP therapy. He was treated with eltrombopag for the last 2 months and had inferior myocardial infarction despite that having no additional risk factors for coronary heart disease. PMID- 26560494 TI - Prospects for the future of prostate cancer vaccines. AB - Cancer therapy is undergoing a revolution fueled by clinical data demonstrating that the immune system has significant anti-tumor capability. Although the main focus of this revolution currently rests upon immune checkpoint inhibitors in diseases such as melanoma, lung and bladder cancer, it was actually a therapeutic cancer vaccine in prostate cancer that provided the first data demonstrating that a modern immunotherapy, beyond cytokines, could enhance clinical outcomes. As immunotherapy is poised to take center stage among cancer therapies, the role of cancer vaccines remains somewhat undefined in prostate cancer, though emerging data suggest that vaccines could play a crucial therapeutic role. PMID- 26560495 TI - The Expression Status and Prognostic Value of Cancer Stem Cell Biomarker CD133 in Cutaneous Squamous Cell Carcinoma. AB - IMPORTANCE: The CD133 protein has been considered a key biomarker of cancer stem cells in various cancers. However, the expression status and prognostic significance of CD133 in cutaneous squamous cell carcinoma (cSCC) are poorly understood. OBJECTIVE: To investigate the expression of cancer stem cell biomarker CD133 in cSCC tissue and its effect on clinicopathological features and outcomes in patients with cSCC. DESIGN, SETTING, AND PARTICIPANTS: Immunohistochemistry was performed on a tissue microarray to investigate the expression levels of CD133 in cSCC tissue. Receiver operating characteristic curve analysis, Kaplan-Meier plots, and a Cox proportional hazards regression model were applied to analyze the data. Samples were obtained from the archives of the First Affiliated Hospital, Sun Yat-Sen University Cancer Center, and Guangzhou Institute of Dermatology and Venerology. In total, 165 paraffin embedded clinicopathological samples from 165 patients were obtained from the archives of hospitals between June 1, 1996, and December 31, 2010. Follow-up data were available for these cases. MAIN OUTCOMES AND MEASURES: The CD133 expression in cSCC tissue, correlation of CD133 expression with clinicopathological features of cSCC, and association of CD133 expression with prognosis in patients with cSCC. RESULTS: Based on the receiver operating characteristic curves, the cutoff value for high CD133 expression was defined as greater than 65% of tumor cells positively stained. High CD133 expression was observed in 50.9% (84 of 165) of the cSCC samples and in 16.7% (5 of 30) of adjacent nonmalignant epithelial tissue samples (P = .001). High CD133 expression was positively correlated with poorly differentiated cSCC (48.0% [73 of 84] for well to moderately differentiated vs 84.6% [11 of 84] for poorly differentiated, P = .01) and with advanced tumor stage (45.5% [55 of 84] for stage I-II vs 65.9% [29 of 84] for stage III, P = .02). In univariable survival analysis, high CD133 expression was correlated with poor prognosis (mean survival, 63.4 vs 95.7 months; P < .001). In multivariable analysis, CD133 expression was an independent prognostic factor for cSCC (hazard ratio, 1.9152; 95% CI, 1.1950-3.3495; P = .02). CONCLUSIONS AND RELEVANCE: High CD133 expression is associated with poorly differentiated and advanced-stage cSCC. High CD133 expression was also correlated with poor prognosis in patients with cSCC. It may serve as a useful biomarker to predict prognosis in patients with cSCC. PMID- 26560497 TI - WITHDRAWN: S-adenosyl-L-methionine for alcoholic liver diseases. PMID- 26560496 TI - Serine 1179 Phosphorylation of Endothelial Nitric Oxide Synthase Increases Superoxide Generation and Alters Cofactor Regulation. AB - Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. In addition to producing NO, eNOS can also generate superoxide (O2-.) in the absence of the cofactor tetrahydrobiopterin (BH4). Previous studies have shown that bovine eNOS serine 1179 (Serine 1177/human) phosphorylation critically modulates NO synthesis. However, the effect of serine 1179 phosphorylation on eNOS superoxide generation is unknown. Here, we used the phosphomimetic form of eNOS (S1179D) to determine the effect of S1179 phosphorylation on superoxide generating activity, and its sensitivity to regulation by BH4, Ca2+, and calmodulin (CAM). S1179D eNOS exhibited significantly increased superoxide generating activity and NADPH consumption compared to wild-type eNOS (WT eNOS). The superoxide generating activities of S1179D eNOS and WT eNOS did not differ significantly in their sensitivity to regulation by either Ca2+ or CaM. The sensitivity of the superoxide generating activity of S1179D eNOS to inhibition by BH4 was significantly reduced compared to WT eNOS. In eNOS-overexpressing 293 cells, BH4 depletion with 10mM DAHP for 48 hours followed by 50ng/ml VEGF for 30 min to phosphorylate eNOS S1179 increased ROS accumulation compared to DAHP-only treated cells. Meanwhile, MTT assay indicated that overexpression of eNOS in HEK293 cells decreased cellular viability compared to control cells at BH4 depletion condition (P<0.01). VEGF-mediated Serine 1179 phosphorylation further decreased the cellular viability in eNOS-overexpressing 293 cells (P<0.01). Our data demonstrate that eNOS serine 1179 phosphorylation, in addition to enhancing NO production, also profoundly affects superoxide generation: S1179 phosphorylation increases superoxide production while decreasing sensitivity to the inhibitory effect of BH4 on this activity. PMID- 26560498 TI - Quinoidal Oligo(9,10-anthryl)s with Chain-Length-Dependent Ground States: A Balance between Aromatic Stabilization and Steric Strain Release. AB - Quinoidal pi-conjugated polycyclic hydrocarbons have attracted intensive research interest due to their unique optical/electronic properties and possible magnetic activity, which arises from a thermally excited triplet state. However, there is still lack of fundamental understanding on the factors that determine the electronic ground states. Herein, by using quinoidal oligo(9,10-anthryl)s, it is demonstrated that both aromatic stabilisation and steric strain release play balanced roles in determining the ground states. Oligomers with up to four anthryl units were synthesised and their ground states were investigated by electronic absorption and electron spin resonance (ESR) spectroscopy, assisted by density functional theory (DFT) calculations. The quinoidal 9,10-anthryl dimer 1 has a closed-shell ground state, whereas the tri- (2) and tetramers (3) both have an open-shell diradical ground state with a small singlet-triplet gap. Such a difference results from competition between two driving forces: the large steric repulsion between the anthryl/phenyl units in the closed-shell quinoidal form that drives the molecule to a flexible open-shell diradical structure, and aromatic stabilisation due to the gain of more aromatic sextet rings in the closed-shell form, which drives the molecule towards a contorted quinoidal structure. The ground states of these oligomers thus depend on the overall balance between these two driving forces and show chain-length dependence. PMID- 26560499 TI - Underlying Cortical Dysplasia as Risk Factor for Traumatic Epilepsy: An Animal Study. AB - Traumatic brain injury (TBI) is a significant risk factor for development of epilepsy in humans. It is unclear, however, why some persons are at an increased risk of becoming epileptic, while others recover from the TBI seizure-free. We previously showed that the presence of a proepileptic pathology increases the risk of epilepsy in an animal model of cortical dysplasia (CD) after a secondary insult, which we described as the "second hit". Here we sought to evaluate the prevalence of epileptic activity and seizures in CD after a moderate TBI to determine the influence of dysplastic pathology on TBI-induced epileptogenesis. CD was generated in rats through in utero irradiation (the "first hit"). Nondysplastic and CD rats were surgically implanted with EEG electrodes. Craniotomies were performed over the pre-central cortex, and rats were given a moderate TBI using the lateral fluid percussion injury device. Rats were monitored with chronic EEG and video. EEG data were analyzed for the occurrence of interictal spikes and epileptic EEG seizure patterns. Brains were harvested and evaluated histologically. Spontaneous seizures are more prominent and occur earlier in rats with CD after a moderate TBI compared with nondysplastic control rats. All of the CD animals exhibited interictal spiking after TBI, while only a portion of nondysplastic animals produced spikes. These results suggest that the presence of a proepileptic pathology may increase the risk for the development of epilepsy after TBI. Diagnosis and treatment of TBI may depend on underlying pathologies contributing to epilepsy after a brain injury. PMID- 26560500 TI - Electroanatomic mapping systems (CARTO/EnSite NavX) vs. conventional mapping for ablation procedures in a training program. AB - BACKGROUND: Three-dimensional electroanatomic mapping (EAM) systems reduce radiation exposure when radio frequency catheter ablation (RFCA) procedures are performed by well-trained senior operators. Given the steep learning curve associated with complex RFCA, trainees and their mentors must rely on multiple imaging modalities to maximize safety and success, which might increase procedure and fluoroscopy times. The objective of the present study is to determine if 3-D EAM (CARTO and ESI-NavX) improves procedural outcomes (fluoroscopy time, radio frequency time, procedure duration, complication, and success rates) during CA procedures as compared to fluoroscopically guided conventional mapping alone in an academic teaching hospital. METHODS: We analyzed a total of 1070 consecutive RFCA procedures over an 8-year period for fluoroscopic time stratified by ablation target and mapping system. Multivariate logistic regression and adjusted odds ratios were calculated for each variable. RESULTS: No statistically significant differences in acute success rates were noted between conventional and 3-D mapping cases [CARTO (p = 0.68) or ESI-NavX (p = 0.20)]. Moreover, complication rates were also not significantly different between CARTO (p = 0.23) and ESI-NavX (p = 0.53) when compared to conventional mapping. Procedure, radio frequency, and fluoroscopy times were significantly longer with CARTO and ESI NavX versus conventional mapping [fluoroscopy time: CARTO, 28.3 min; ESI, 28.5 min; and conventional, 24.3 min; p < 0.001)]. CONCLUSIONS: The use of 3-D EAM systems during teaching cases significantly increases radiation exposure when compared with conventional mapping. These findings suggest a need to develop alternative training strategies that enhance confidence and safety during catheter manipulation and allow for reduced fluoroscopy and procedure times during RFCA. PMID- 26560501 TI - A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration. AB - Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas. PMID- 26560503 TI - Cerebrospinal Fluid Biomarkers Predict Clinical Evolution in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment. AB - BACKGROUND: Determination of Alzheimer's disease (AD) by cerebrospinal fluid (CSF) biomarkers - 42-amino-acid amyloid-beta (Abeta42), total tau and phosphorylated tau (p-tau) - has demonstrated high validity for detecting AD neuropathological changes. However, their prognostic utility to predict the onset of dementia in predementia subjects is still questioned. We aimed to study the prospective clinical evolution of a group of subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) and to determine the prognostic capacity of AD CSF biomarkers. METHODS: 149 subjects with MCI or SCD, not meeting dementia criteria, underwent a prospective clinical, neuropsychological and CSF biomarker study. Patients were initially classified as SCD or MCI following internationally accepted criteria. CSF sampling was obtained and analysed following consensus protocols. Neuropsychological and clinical evaluations were conducted at the follow-up. Statistical analysis considering the final clinical diagnosis, regression analysis to define risk factors and survival curves for progression were made. RESULTS: 72.4% of subjects (83% MCI and 27% SCD) with a pathological CSF ratio (Abeta42/p-tau) met criteria for dementia during the 5 year follow-up versus 18.7% of subjects from the group with a normal ratio. The pathological CSF ratio was a powerful marker of risk for AD dementia (OR 27.1; 95% CI 10.3-71.2). Kaplan-Meier survival curves showed that only 15% of subjects with a pathological CSF ratio remained free of AD dementia at 5 years of follow up. All subjects who reverted to normal cognition presented a normal CSF profile at baseline. CONCLUSION: An abnormal AD CSF biomarker profile in predementia subjects is a powerful predictor of cognitive and/or functional decline in the medium term. PMID- 26560502 TI - Assessment of risk of peripheral vascular disease and vascular care capacity in low- and middle-income countries. AB - BACKGROUND: This study aimed to describe national peripheral vascular disease (PVD) risk and health burden, and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in low- and middle-income countries was defined, and capacity improvement priorities were identified. METHODS: Data to estimate PVD risk factor burden were obtained from the World Health Organization Study on Global Ageing and Adult Health (SAGE), Ghana, and the Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) database. In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were described. RESULTS: From the SAGE database, there were 4305 respondents aged at least 50 years with data to estimate PVD risk. Of these, 57.4 per cent were at moderate to risk high of PVD with at least three risk factors; extrapolating nationally, the estimate was 1 654 557 people. Based on IHME GBD data, the estimated disability-adjusted life years incurred from PVD increased fivefold from 1990 to 2010 (from 6.3 to 31.7 per 100 000 persons respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, and in perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. CONCLUSION: Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of PVD falling on healthcare systems in low- and middle-income countries. These countries are not well equipped to handle vascular surgical care, and rapid development of such capacity would be difficult and expensive. PMID- 26560504 TI - Long-term functional results after open partial horizontal laryngectomy type IIa and type IIIa: A comparison study. AB - BACKGROUND: The purpose of this study was to compare long-term swallowing, voice results, and quality of life (QOL) after open partial horizontal laryngectomy (OPHL) type IIa and type IIIa. METHODS: Twenty-three patients after OPHL type IIa and 18 patients after OPHL type IIIa were involved. Swallowing skills and neoglottis' motility and vibrations were videoendoscopically assessed. Aerodynamic measures, spectrogram analysis, aspiration pneumonia, body weight variations, and voice perceptual assessment were performed. Generic voice-related and swallowing-related QOL were assessed. Data were statistically compared using Mann-Whitney U test or Fisher exact tests, as appropriate. RESULTS: Significant differences were found only for the residue with solids and for the intelligibility (I) parameter of the overall quality impression and intelligibility, additive and unnecessary noise, speech fluency, and presence of voiced segments scale with patients of the OPHL type IIIa group showing worse performances than the OPHL type IIa group. CONCLUSION: Patients who underwent OPHL type IIa and type IIIa show comparable long-term functional outcomes. OPHL type IIIa represents a valid surgical alternative to OPHL type IIa. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1427-E1435, 2016. PMID- 26560506 TI - A Youthful Age Identity Mitigates the Effect of Post-Traumatic Stress Disorder Symptoms on Successful Aging. PMID- 26560505 TI - Expression of Forkhead box M1 in soft tissue leiomyosarcoma: Clinicopathologic and in vitro study using a newly established cell line. AB - Leiomyosarcoma (LMS) of soft tissue is a sarcoma with smooth-muscle differentiation, and conventional chemotherapy does not improve its outcome. The application of novel antitumor agents and precise prognostication has been demanded. The expression of the protein Forkhead box M1 (FOXM1), a member of the FOX family, is considered an independent predictor of poor survival in many cancers and sarcomas. However, the expression status of FOXM1 in LMS is poorly understood. The purposes of this study were to examine the correlation between the expression of FOXM1 and clinicopathologic or prognostic factors and to clarify the efficacy of FOXM1 target therapy in LMS. We evaluated the immunohistochemical expressions of FOXM1 using 123 LMS tumor specimens. Univariate and multivariate survival analyses revealed that FOXM1 expression was associated with poor prognosis in LMS. An in vitro study was then carried out to examine the antitumor effect of a FOXM1 inhibitor (thiostrepton) and siRNA on a novel LMS cell line, TC616. We also assessed the efficacy of the combined use of doxorubicin and thiostrepton. Thiostrepton showed dose-dependent antitumor activity and TC616 cells treated with the combination of thiostrepton and doxorubicin showed lower proliferation compared to those treated with either drug individually. FOXM1 interruption by siRNA decreased cell proliferation and increased chemosensitivity. In conclusion, FOXM1 has potential to be a therapeutic target for LMS. PMID- 26560507 TI - The Impact of Young Onset Dementia on Informal Caregivers Compared with Late Onset Dementia: Results from the NeedYD Study. AB - OBJECTIVES: The impact of the dementia might be more severe for caregivers of people with young onset dementia (YOD) compared with those who care for someone with late onset dementia (LOD), as a young age among caregivers has been identified as a predictor of increased burden. The present study compares well being between LOD and YOD caregivers longitudinally because this knowledge is essential in order to develop adequate support programs. DESIGN, SETTING, AND PARTICIPANTS: 220 YOD and 108 LOD patient-caregiver dyads were included from two prospective cohorts with a 2-year follow up. To assess well-being we used the Short Sense of Competence Questionnaire, the RAND-36, the Symptom Checklist 90, and the Montgomery Asberg Depression Rating Scale. The severity and the course of the different measures used to describe caregiver burden were analyzed with linear mixed models. RESULTS: Caregivers in both groups experienced high levels of physical and psychological complaints, mild depressive symptoms, lower health related quality of life (HRQoL), and decreased feelings of competence. The severity and the course of most measures were similar in both groups, although HRQoL on both the physical and the mental domain was lower for the YOD caregivers. CONCLUSIONS: The number of actual psychological and physical complaints does not differ between YOD and LOD caregivers. YOD caregivers have greater perceived difficulties in daily life because of these complaints, however. PMID- 26560509 TI - Examining the Pathways Between Self-Awareness and Well-Being in Mild to Moderate Alzheimer Disease. AB - OBJECTIVE: To investigate the relationship between awareness of memory loss and psychological well-being in a nonclinically depressed sample of participants with mild to moderate Alzheimer disease (AD). METHODS: Study participants (N = 104) enrolled through Columbia University Medical Center and the University of Pennsylvania completed clinical and cognitive assessments. Participants were rated with regard to their degree of awareness of memory deficits and completed questionnaires relating to their psychological well-being, including mood and quality of life (QOL). Mediating models were used to establish the relationship between awareness, depression, and QOL and to examine potential mediators of awareness and depression, including psychological distress, objective memory deficits, and negative self-ratings. RESULTS: There was a direct association between awareness of memory deficits and depressed mood but not awareness and QOL. However, there was an indirect association between awareness and QOL through depression. Neither psychological distress, memory deficits, nor negative self ratings mediated the relationship between awareness and depression. CONCLUSION: Awareness is associated with depressed mood in nonclinically depressed participants with mild to moderate AD. However, depressed mood does not appear to reflect the direct psychological reaction to awareness of memory loss. Moreover, awareness has only an indirect association with QOL via depressed mood. These results suggest that preserved awareness does not have a direct negative impact on overall psychological well-being in AD. PMID- 26560508 TI - Prevalence of Post-Traumatic Stress Disorder in Aging Vietnam-Era Veterans: Veterans Administration Cooperative Study 569: Course and Consequences of Post Traumatic Stress Disorder in Vietnam-Era Veteran Twins. AB - OBJECTIVE: The prevalence of post-traumatic stress disorder (PTSD) among aging Vietnam-era veterans is not well characterized. METHODS: In a cross-sectional study, 5,598 male Vietnam-era veterans and members of the Vietnam Era Twin Registry were assessed for PTSD using the Composite International Diagnostic Interview. Current symptoms were measured with the PTSD Checklist (PCL). PTSD was estimated according to age (<60 or >= 60) and Vietnam theater service. RESULTS: The lifetime prevalence of PTSD in theater veterans aged at least 60 years was 16.9% (95% CI: 13.9%-20.5%) and higher than the 5.5% (95% CI: 4.3%-7.0%) among nontheater veterans. Among veterans younger than 60 years, the comparable prevalence was 22.0% for theater (95% CI: 16.7%-28.4%) and 15.7% for nontheater (95% CI: 13.4%-18.2%) veterans. Similar results were found for theater service and current PTSD prevalence (past 12 months). PCL scores were significantly higher in theater compared with nontheater veterans in both younger and older cohorts. In both the younger and older cohorts significant differences in lifetime and current PTSD prevalence and PCL scores persisted in theater service discordant twin pairs. CONCLUSION: Vietnam service is related to elevated PTSD prevalence and current symptom burden in aging veterans. More than 30 years after the end of the Vietnam conflict, many veterans continue to suffer from PTSD, which highlights the need for continuing outreach throughout the life course. PMID- 26560510 TI - Dual Trajectories of Depression and Cognition: A Longitudinal Population-Based Study. AB - OBJECTIVE: To examine the relationships over time between dual trajectories of depressive symptoms and several cognitive domains. METHODS: In a 5-year longitudinal study, 1,978 randomly selected individuals aged 65+ years at recruitment were assessed annually. Repeated measures were of depressive symptoms on the modified Center for Epidemiologic Studies Depression Scale and composite scores in the cognitive domains of attention, executive function, memory, language, and visuospatial function. Latent class trajectories were identified for depression and for each cognitive domain and their associations investigated using dual trajectory modeling. Cognitive trajectories with z scores below -1 were designated as persistently low. RESULTS: Five depressive symptom trajectories were observed: rarely depressed (60.5%); low-grade, decreasing symptoms (18.5%); low-grade, increasing symptoms (9.6%); moderate-grade symptoms (7.4%); and consistent higher-grade symptoms (4.0%). For each cognitive domain six trajectories were observed. The rarely depressed and low-grade decreasing symptom groups were the least likely to have persistently low cognition. The symptom trajectory most strongly associated with persistently low functioning in each domain was not the higher-grade group but rather the low-grade increasing group in the case of attention and the moderate-grade trajectory in the other four domains. CONCLUSION: Consistently higher-grade depressive symptoms are less strongly associated with poor cognitive functioning than with either moderate- or low-grade increasing depressive symptom trajectories, over time and across different domains. Examining both depression and cognition longitudinally allows heterogeneity of both to be addressed, revealing latent groups with potential diagnostic and prognostic implications. PMID- 26560511 TI - Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial. AB - OBJECTIVES: Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia. DESIGN: Randomized, double-blind, placebo controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each. SETTING: Two hospital sites in The Netherlands, September 2011 to December 2013. PARTICIPANTS: Patients with dementia and clinically relevant NPS. INTERVENTION: Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout. MEASUREMENTS: Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover. RESULTS: 22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred. CONCLUSIONS: This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies. PMID- 26560513 TI - Self-Rated and Caregiver-Rated Quality of Life in Alzheimer Disease with a Focus on Evolving Patient Ability to Respond to Questionnaires: 5-Year Prospective ALSOVA Cohort Study. AB - OBJECTIVE: To examine and compare self-rated and caregiver-rated measures of quality of life (QoL) in relation to disease progression in patients with very mild or mild Alzheimer disease (AD) and at what disease stage patient's ability to respond to QoL questionnaires with or without assistance begins to diminish. METHODS: 236 patients with very mild or mild AD and their family caregivers from three Finnish hospital districts participated in this prospective, longitudinal study with 5 years of follow-up. Three patient-reported instruments were used to assess QoL (the generic 15D, the Quality of Life in Alzheimer Disease [QoL-AD] questionnaire, and a visual analogue scale) as well as one caregiver-rated assessment of patient QoL (QoL-AD). AD severity was evaluated with the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB). RESULTS: All self- and caregiver rated QoL estimates correlated with AD severity. The self- and caregiver-rated QoL scores began to diverge even with very mild cognitive impairment after CDR SOB reached 4, the value that corresponds with a Mini-Mental State Examination (MMSE) score of 25-30. Patients also began to need assistance in responding to questionnaires at very early stages of AD (CDR-SOB score: 4-6). Furthermore, their ability to respond to QoL questionnaires with or without assistance declined after CDR-SOB reached 11 points, a value that correlates with an early moderate stage of AD and MMSE score of 11-20. CONCLUSIONS: AD patients' self rated QoL ratings are much more insensitive to disease progression than caregiver ratings. PMID- 26560514 TI - Recent updates in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD), characterized by chronic airways inflammation and progressive airflow limitation, is a common, preventable and treatable disease. Worldwide, COPD is a major cause of morbidity and mortality; smoking tobacco is the most important risk factor. This translational review of recent updates in COPD care for the primary care audience, includes recommendations from the 2015 Global Initiative for chronic obstructive lung disease (GOLD) report on diagnosis, pharmacological and non-pharmacological treatment, prevalence of comorbidities, management of exacerbations and the asthma and COPD overlap syndrome, with a focus on the importance and benefit of physical activity and exercise in COPD patients. Exacerbations and comorbidities contribute to the overall severity of COPD in individual patients. Management of exacerbations includes reducing the impact of the current exacerbation and preventing development of subsequent episodes. Healthcare professionals need to be alert to comorbidities, such as cardiovascular disease, anxiety/depression, lung cancer, infections and diabetes, which are common in COPD patients and can have a significant impact on HRQoL and prognosis. Pulmonary rehabilitation is recommended by a number of guidelines for all symptomatic COPD patients, regardless of severity, and involves exercise training, patient education, nutritional advice and psychosocial support. At all stages of COPD, regular physical activity and exercise can aid symptom control, improve HRQoL, reduce rates of hospitalization, and improve morbidity and respiratory mortality. Healthcare professionals play a pivotal role in improving HRQoL and health related outcomes in COPD patients to meet their specific needs and in providing appropriate diagnosis, management and advice on smoking cessation. PMID- 26560512 TI - Relationship Between Cerebrovascular Risk, Cognition, and Treatment Outcome in Late-Life Psychotic Depression. AB - OBJECTIVE: To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults. METHODS: The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT. RESULTS: Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome. CONCLUSION: This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults. PMID- 26560515 TI - CHEST Annual meeting 2015. PMID- 26560517 TI - Development and demonstration of a state model for the estimation of incidence of partly undetected chronic diseases. AB - BACKGROUND: Estimation of incidence of the state of undiagnosed chronic disease provides a crucial missing link for the monitoring of chronic disease epidemics and determining the degree to which changes in prevalence are affected or biased by detection. METHODS: We developed a four-part compartment model for undiagnosed cases of irreversible chronic diseases with a preclinical state that precedes the diagnosis. Applicability of the model is tested in a simulation study of a hypothetical chronic disease and using diabetes data from the Health and Retirement Study (HRS). RESULTS: A two dimensional system of partial differential equations forms the basis for estimating incidence of the undiagnosed and diagnosed disease states from the prevalence of the associated states. In the simulation study we reach very good agreement between the estimates and the true values. Application to the HRS data demonstrates practical relevance of the methods. DISCUSSION: We have demonstrated the applicability of the modeling framework in a simulation study and in the analysis of the Health and Retirement Study. The model provides insight into the epidemiology of undiagnosed chronic diseases. PMID- 26560518 TI - Weather and Prey Predict Mammals' Visitation to Water. AB - Throughout many arid lands of Africa, Australia and the United States, wildlife agencies provide water year-round for increasing game populations and enhancing biodiversity, despite concerns that water provisioning may favor species more dependent on water, increase predation, and reduce biodiversity. In part, understanding the effects of water provisioning requires identifying why and when animals visit water. Employing this information, by matching water provisioning with use by target species, could assist wildlife management objectives while mitigating unintended consequences of year-round watering regimes. Therefore, we examined if weather variables (maximum temperature, relative humidity [RH], vapor pressure deficit [VPD], long and short-term precipitation) and predator-prey relationships (i.e., prey presence) predicted water visitation by 9 mammals. We modeled visitation as recorded by trail cameras at Sevilleta National Wildlife Refuge, New Mexico, USA (June 2009 to September 2014) using generalized linear modeling. For 3 native ungulates, elk (Cervus Canadensis), mule deer (Odocoileus hemionus), and pronghorn (Antilocapra americana), less long-term precipitation and higher maximum temperatures increased visitation, including RH for mule deer. Less long-term precipitation and higher VPD increased oryx (Oryx gazella) and desert cottontail rabbits (Sylvilagus audubonii) visitation. Long-term precipitation, with RH or VPD, predicted visitation for black-tailed jackrabbits (Lepus californicus). Standardized model coefficients demonstrated that the amount of long-term precipitation influenced herbivore visitation most. Weather (especially maximum temperature) and prey (cottontails and jackrabbits) predicted bobcat (Lynx rufus) visitation. Mule deer visitation had the largest influence on coyote (Canis latrans) visitation. Puma (Puma concolor) visitation was solely predicted by prey visitation (elk, mule deer, oryx). Most ungulate visitation peaked during May and June. Coyote, elk and puma visitation was relatively consistent throughout the year. Within the diel-period, activity patterns for predators corresponded with prey. Year-round water management may favor species with consistent use throughout the year, and facilitate predation. Providing water only during periods of high use by target species may moderate unwanted biological costs. PMID- 26560516 TI - Neuropilin-2 Regulates Endosome Maturation and EGFR Trafficking to Support Cancer Cell Pathobiology. AB - Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat and FYVE-domain-containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies. PMID- 26560519 TI - Interrelationships between glutamine and citrulline metabolism. AB - PURPOSE OF REVIEW: This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. RECENT FINDINGS: Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter randomized controlled trial resulted in increased mortality in the glutamine-supplemented group. Within this context, defining the contribution of glutamine to the production of citrulline, and thus to de-novo arginine synthesis, has become a pressing issue. SUMMARY: The beneficial effects of glutamine supplementation may be partially mediated by the effects of glutamine on citrulline synthesis by the gut and the de-novo synthesis of arginine by the kidney and other tissues. Although there is no strong evidence to support that glutamine is a major precursor for citrulline synthesis in humans, glutamine has the potential to increase overall gut function and in this way increase citrulline production. PMID- 26560521 TI - The biology of the metabolic syndrome and aging. AB - PURPOSE OF REVIEW: Aging of the world population is a major contributor to the growing prevalence of the metabolic syndrome, as older persons are frequently affected by the constellation of cardiovascular and metabolic risk factors that constitute the syndrome. The metabolic syndrome has been related to the increasing prevalence of obesity, which is escalating even among older age groups. The present review covers data on the novel proposed biological mediators of the metabolic syndrome, which are as well linked to the aging process. RECENT FINDINGS: Relevant biological mediators of metabolic syndrome and unhealthy aging include sarcopenic obesity, insulin resistance with ectopic fat accumulation, magnesium metabolism alterations, systemic and hypothalamic inflammation, shortening of telomeres length, epigenetics, and circadian rhythm disturbances. SUMMARY: Metabolic syndrome is related to increased accumulation of central adiposity and ectopic fat infiltration in the skeletal muscle and the liver, linked to overeating and sedentarism with deleterious consequences in late life. Obesity may be complicated with sarcopenia, which refers to loss of muscle mass, strength, and quality in older populations. Prevention of obesity and metabolic syndrome is a priority through the promotion of healthier lifestyles and policies for sugar and saturated fats, which might be widely implemented. PMID- 26560520 TI - Protein anabolic resistance in cancer: does it really exist? AB - PURPOSE OF REVIEW: Preventing unintentional weight and muscle loss is of crucial importance to maintain the condition and well-being of patients with cancer, improve treatment response and tolerance, and prolong survival. Anabolic resistance might explain why some cancer patients do not respond to nutritional intervention, but does recent evidence actually support this? We will discuss recent literature that casts doubt on attenuated anabolic potential in cancer. RECENT FINDINGS: Although anabolic resistance was observed in the past, more recent studies have shown that advanced cancer patients have an anabolic potential after intake of high-quality proteins. Furthermore, a consistent linear relationship is observed in cancer between (essential) amino acid availability from the diet and net protein gain. The studied cancer patients, however, were often characterized by a normal or obese body weight, following the trend in the general population, and mild systemic inflammation. Factors like recent chemotherapy, surgery, or cachexia do not seem to attenuate the anabolic potential to feeding. SUMMARY: Cancer patients have a normal anabolic potential which relates to the amount of essential amino acids in the meal. It remains to be determined if this is also the case in weak cancer patients with a short life expectancy and high systemic inflammation. PMID- 26560522 TI - The conserved role of protein restriction in aging and disease. AB - PURPOSE OF REVIEW: Dietary interventions are effective strategies for preventing disease and promoting health span. Many of the effects of dietary restriction are linked to amino acid and protein levels and their regulation of nutrient signaling pathways. Thus, protein restriction is a promising therapeutic strategy for preventing aging-related diseases and extending life span. RECENT FINDINGS: Studies in yeast and flies have shown that amino acid restriction promotes longevity and protection. In rodents, protein restriction extends life span and alleviates detrimental aging phenotypes. Finally, clinical trials in middle-aged adults have demonstrated the role of a protein-restricted diet in promoting health span. Interestingly, the population over the age of 65 may not benefit from severe protein restriction potentially because of the increased physiological decline that leads to decreased amino acid absorption and altered protein synthesis. SUMMARY: Protein restriction can have profound effects on health and longevity, but excessive restriction is detrimental, particularly in the very old. The investigation of the mechanisms that modulate nutrient-sensing pathways is important to understand how regulation of protein intake can optimize health span and longevity. PMID- 26560523 TI - Mood, food, and cognition: role of tryptophan and serotonin. AB - PURPOSE OF REVIEW: Food is not only necessary as a metabolic fuel for the body, it becomes more and more evident that there exists an association between food and brain functions like mood and cognition. Tryptophan represents a key element for brain functioning, because of its role as a precursor for production of neurotransmitter serotonin (5-hydroxytryptamine). In clinical conditions, which involve chronic immune system activation or under cytokine therapy, lower tryptophan levels because of high catabolism of tryptophan as indicated by the kynurenine to tryptophan ratio are common and often associate with depressive mood. RECENT FINDINGS: Studies in the in vitro model of mitogen-stimulated peripheral blood mononuclear cells revealed that several phytocompounds, mainly antioxidants like polyphenols and vitamins, can interfere with inflammatory signaling cascades including tryptophan breakdown. If extrapolated to the in vivo situation, such compounds could increase blood and brain tryptophan availability for serotonin production. Although there is some in vivo evidence for the effect of such compounds, outcomes are hardly predictable and most likely depend on the individual's immunological state. SUMMARY: Not only a diet rich in tryptophan but also a diet rich in antioxidants can have a positive impact on mood and cognition. This could be of special relevance for individuals who present with low grade inflammation conditions. PMID- 26560524 TI - The ageing gastrointestinal tract. AB - PURPOSE OF REVIEW: This article reviews the impact of ageing on the gastrointestinal tract, including effects on the absorption of nutrients and drugs and the gastrointestinal tract defence system against ingested pathogens. RECENT FINDINGS: Recent publications support earlier observations of an age related selective decline in gut function including changes in taste, oesophageal sphincter motility, gastric emptying, and neurons of the myenteric plexus related to gut transit which may impact the nutritional status. Ageing is also associated with structural and functional mucosal defence defects, diminished abilities to generate protective immunity, and increased incidence of inflammation and oxidative stress. A number of gastrointestinal disorders occur more frequently in the elderly population. SUMMARY: Alterations in gut function with ageing have particular implications for oesophageal, gastric, and colonic motility. Older individuals are particularly susceptible to malnutrition, postprandial hypotension, dysphagia, constipation, and faecal incontinence. Decrease in the number of nerve cells of the myenteric plexus that impact digestive absorption and the surface area of the small intestine because of degeneration of villi may lead to blunted absorption of nutrients. Impairment of the intestinal immune system as a result of ageing, including the mucosal layer of the gastrointestinal tract, appears to be a significant contributor to the age-related increase in the incidence and severity of infections. PMID- 26560525 TI - Amino acid sensing and activation of mechanistic target of rapamycin complex 1: implications for skeletal muscle. AB - PURPOSE OF REVIEW: This article evaluates recent studies on the mechanisms involved in sensing changes in amino acid availability and activation of the mechanistic target of rapamycin complex 1 (mTORC1). RECENT FINDINGS: mTORC1 is sensitive to changes in amino acid availability and a well known regulator of protein turnover. The mechanisms of amino acid sensing and mTORC1 signaling are emerging with multiple potential sensors (e.g., solute carrier family 38, member 9, lysosomal protein transmembrane 4 beta/solute carrier family 7, member 5 solute carrier family 3, member 2) and signal transducers (e.g., Sestrins, ADP ribosylation factor 1, and microspherule protein 1) identified. Studies in various cell lines have unveiled the importance of the lysosome in amino acid sensing and signal transmission. SUMMARY: Recent discoveries in amino acid sensing highlight a complex scenario, whereby mTORC1 is not merely sensitive to some amino acids and not others, but where specific amino acids are sensed by specific pathways under specific conditions. The physiological purpose of such an arrangement remains to be unraveled, but it would allow mTORC1 to precisely regulate growth during different metabolic conditions. Understanding the mechanisms responsible for sensing amino acid availability and regulating mTORC1 activity is an important prerequisite for the development of nutritional strategies to combat skeletal muscle wasting disorders. PMID- 26560526 TI - Nutrient interface with biology and aging. AB - PURPOSE OF REVIEW: To highlight recent conundrums in the interface of nutrition, biology and aging. RECENT FINDINGS: A Mediterranean diet with extra virgin olive oil, or similar plant-based diets, including five helpings of fruit and vegetables, exercise and nonsmoking are the mainstays of aging successfully. Recent studies have questioned the utility of weight loss in older persons, the use of antioxidant vitamin supplements as well as the appropriate level of sodium intake. The understanding of the role of ethnicity in the levels of vitamin D binding protein has questioned the measurement of 25(OH)vitamin D by itself. Gut microbiota may also appear important for aging. SUMMARY: Continuous scientific advances are leading us to question whether some of our nutrient beliefs need to be altered in older persons. PMID- 26560527 TI - Microbiota and aging. AB - PURPOSE OF REVIEW: This article summarizes our current knowledge of changes in the intestinal microbiota in elderly people and centenarians. RECENT FINDINGS: Age-related processes comprise specific changes in the intestinal microbiota and related metabolic alterations. They result in 'inflamm-aging', which is associated with age-related inflammatory processes and diseases, including cachexia, frailty, cancer, and metabolic as well as neurological diseases. Age related microbial changes consist of an increase in proteolytic bacteria and a decrease in saccharolytic bacteria. These changes are associated with sarcopenia and longevity, and might be attenuated by pre and probiotics. These findings could explain, at least in part, why probiotics have been successfully used in elderly people for the treatment of respiratory and gastrointestinal infections, and for the enhancement of vaccination responses. SUMMARY: The intestinal microbiota changes with age. These changes are of relevance in regard to morbidity and mortality in the elderly population. Dietetic (probiotics, prebiotics) and other lifestyle interventions might delay, or even reverse, such alterations. PMID- 26560528 TI - Living in interesting times--challenging protein metabolism in the era of the epidemiological shift. PMID- 26560529 TI - Recent developments in percutaneous mitral valve treatment. AB - In recent years, various percutaneous techniques have been introduced for the treatment of mitral regurgitation (MR), including direct leaflet repair, annuloplasty and left ventricular remodeling. Percutaneous mitral repair targets both primary degenerative and secondary mitral valve regurgitation and may be considered in selected high-surgical-risk patients. The assessment of mitral functional anatomy by echocardiography and computed tomography is crucial when selecting the appropriate repair strategy, according to the regurgitant valve lesion and the surrounding anatomy. The ongoing clinical use of new devices in annuloplasty and percutaneous mitral valve replacement is a promising new scenario in the treatment of MR that goes beyond the conventional surgical approach. PMID- 26560530 TI - Transglutaminase inhibitors: a patent review. AB - INTRODUCTION: Transglutaminases (TGases) are a class of enzymes that play multifunctional roles. Their protein-crosslinking activity has been linked to fibrosis and Huntington's disease, their glutamine deamidation activity has been related to celiac disease and their GTP-binding activity has been implicated in cancer. All of these physiological disorders have prompted the development of inhibitors, which has accelerated dramatically over the past decade. AREAS COVERED: This review presents an overview of TGase inhibitors published in the patent literature, from the first compounds developed in the late 1980's, to the current date. This article is focussed on the chemical structure of new inhibitors and their probable mechanism of action. EXPERT OPINION: Comparison of effective TGase inhibitors reveals common structural features that may guide future design. Many of these elements are embodied in the first TGase inhibitor to recently enter into clinical trials. PMID- 26560531 TI - Eco-physiological adaptation shapes the response of calcifying algae to nutrient limitation. AB - The steady increase in global ocean temperature will most likely lead to nutrient limitation in the photic zone. This will impact the physiology of marine algae, including the globally important calcifying coccolithophores. Understanding their adaptive patterns is essential for modelling carbon production in a low-nutrient ocean. We investigated the physiology of Helicosphaera carteri, a representative of the abundant but under-investigated flagellated functional group of coccolithophores. Two strains isolated from contrasting nutrient regimes (South Atlantic and Mediterranean Sea) were grown in phosphorus-replete and phosphorus limited batch cultures. While growing exponentially in a phosphorus-replete medium, the Mediterranean strain exhibited on average 24% lower growth rate, 36% larger coccosphere volume and 21% lower particulate inorganic carbon (PIC) production than the Atlantic strain. Under phosphorus limitation, the same strain was capable of reaching a 2.6 times higher cell density than the Atlantic strain due to lower phosphorus requirements. These results suggest that local physiological adaptation can define the performance of this species under nutrient limitation. PMID- 26560533 TI - Simultaneous Detection of Major Drug Resistance Mutations of HIV-1 Subtype B Viruses from Dried Blood Spot Specimens by Multiplex Allele-Specific Assay. AB - A multiplex allele-specific (MAS) assay has been developed for the detection of HIV-1 subtype C drug resistance mutations (DRMs). We have optimized the MAS assay to determine subtype B DRMs in dried blood spots (DBS) collected from patients on antiretroviral therapy. The new assay accurately detected DRMs, including low abundance mutations that were often missed by Sanger sequencing. PMID- 26560532 TI - Multicenter Evaluation of the Xpert Norovirus Assay for Detection of Norovirus Genogroups I and II in Fecal Specimens. AB - Norovirus is the most common cause of sporadic gastroenteritis and outbreaks worldwide. The rapid identification of norovirus has important implications for infection prevention measures and may reduce the need for additional diagnostic testing. The Xpert Norovirus assay recently received FDA clearance for the detection and differentiation of norovirus genogroups I and II (GI and GII), which account for the vast majority of infections. In this study, we evaluated the performance of the Xpert Norovirus assay with both fresh, prospectively collected (n = 914) and frozen, archived (n = 489) fecal specimens. A Centers for Disease Control and Prevention (CDC) composite reference method was used as the gold standard for comparison. For both prospective and frozen specimens, the Xpert Norovirus assay showed positive percent agreement (PPA) and negative percent agreement (NPA) values of 98.3% and 98.1% for GI and of 99.4% and 98.2% for GII, respectively. Norovirus prevalence in the prospective specimens (collected from March to May of 2014) was 9.9% (n = 90), with the majority of positives caused by genogroup II (82%, n = 74). The positive predictive value (PPV) of the Xpert Norovirus assay was 75% for GI-positive specimens, whereas it was 86.5% for GII-positive specimens. The negative predictive values (NPV) for GI and GII were 100% and 99.9%, respectively. PMID- 26560534 TI - HemaSpot, a Novel Blood Storage Device for HIV-1 Drug Resistance Testing. AB - HemaSpot, a novel dried-blood storage filter device, was used for HIV-1 pol resistance testing in 30 fresh United States blood samples and 54 previously frozen Kenyan blood samples. Genotyping succeeded in 79% and 58% of samples, respectively, improved with shorter storage and higher viral load, and had good (86%) resistance mutation concordance to plasma. PMID- 26560535 TI - Two Serious Cases of Infection with Clostridium celatum after 40 Years in Hiding? AB - Clostridium celatum [ce.la'tum. L. adj. celatum hidden] has been known since 1974, when it was isolated from human feces. In 40 years, no association with human infection has been reported. In this work, we present two serious cases of infection with the anaerobic Gram-positive rod Clostridium celatum. PMID- 26560536 TI - Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013. AB - The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development. PMID- 26560537 TI - Robust Real-Time Reverse Transcription-PCR for Detection of Foot-and-Mouth Disease Virus Neutralizing Carryover Contamination. AB - During an outbreak of foot-and-mouth disease (FMD), real-time reverse transcription-PCR (rRT-PCR) is the most commonly used diagnostic method to detect viral RNA. However, while this assay is often conducted during the outbreak period, there is an inevitable risk of carryover contamination. This study shows that the carryover contamination can be prevented by the use of target-specific restriction endonuclease in that assay. PMID- 26560538 TI - Peaks of Promise and Peril: Screening for Antibiotic Resistance by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. AB - An article in this issue of the Journal of Clinical Microbiology (J.-H. Youn, S. K. Drake, R. A. Weingarten, K. M. Frank, J. P. Dekker, and A. F. Lau, J Clin Microbiol 53:35-42, 2015, http://dx.doi.org/10.1128/JCM.01643-15) describes the use of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for the detection of organisms carrying a blaKPC-containing plasmid. This powerful and promising application highlights the challenges of using MALDI-TOF mass spectrometry for purposes other than organism identification. PMID- 26560539 TI - Occurrence of Fungal DNA Contamination in PCR Reagents: Approaches to Control and Decontamination. AB - Nucleic acid amplification techniques permitting sensitive and rapid screening in patients at risk for invasive fungal infections are an important addition to conventional fungal diagnostic methods. However, contamination with fungal DNA may be a serious threat to the validity of fungal amplification-based assays. Besides rigorous handling procedures to avoid false-positive test results from exogenous sources, we have implemented protocols for comprehensive assessment of fungal contamination in all materials involved in the analytical process. Traces of fungal DNA were found in different commercially available PCR reagents, including lyophilized primers, TaqMan probes, and master mix solutions. These contaminants resulted in a considerable rate of false-positive tests in panfungal real-time PCR analysis. To address this problem, we have established a decontamination protocol based on the activity of a double-strand specific DNase. Using this approach, we have significantly reduced the frequency of false positive test results attributable to contaminated reagents. On the basis of our findings, we strongly recommend routine monitoring of all reagents used in fungal PCR assays for the presence of relevant contaminants. As long as fungal-grade reagents are not readily available, pretreatment methods facilitating elimination of fungal DNA are critical for reducing the risk of false-positive results in highly sensitive molecular fungal detection assays. PMID- 26560540 TI - Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection. AB - The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively. PMID- 26560541 TI - Misidentification of a Rare Species, Cryptococcus laurentii, by Commonly Used Commercial Biochemical Methods and Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry Systems: Challenges for Clinical Mycology Laboratories. AB - Forty-two putative Cryptococcus laurentii isolates identified by the Vitek 2 system were collected in China. The gold standard, internal transcribed spacer (ITS) sequencing, confirmed that only two isolates were genuine C. laurentii. Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry was able to identify the C. laurentii isolates with an expanded custom database. PMID- 26560542 TI - Comparison of illumigene Group A Streptococcus Assay with Culture of Throat Swabs from Children with Sore Throats in the New Zealand School-Based Rheumatic Fever Prevention Program. AB - Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the illumigene GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the illumigene assay using culture on blood agar as the "gold standard" and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the illumigene assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing. PMID- 26560543 TI - Comparison of Six Automated Treponema-Specific Antibody Assays. AB - Six different Treponema (TP)-specific immunoassays were compared to the fluorescent treponemal antibody absorption (FTA-ABS) test. A total of 615 samples were tested. The overall percent agreement, analytical sensitivity, and analytical specificity of each assay compared to the FTA-ABS test were as follows: Architect Syphilis TP, 99.2%, 96.8%, and 100%; Cobas Syphilis, 99.8%, 99.4%, and 100%; ADVIA Centaur Syphilis, 99.8%, 99.4%, and 100%; HISCL Anti-TP assay kit, 99.7%, 98.7%, and 100%; Immunoticles Auto3 TP, 99.0%, 97.5%, and 99.6%; Mediace TPLA, 98.0%, 98.1%, and 98.0%. All results that were discrepant between the TP-specific assays were associated with samples from noninfectious cases (11 immunoassay false positives and 7 from previous syphilis cases). Our study demonstrated that TP-specific immunoassays generally showed high sensitivities, specificities, and percentages of agreement compared to FTA-ABS, with rare cases of false-positive or false-negative results. Therefore, most TP specific immunoassays are acceptable for use in screening for syphilis. However, it is important to perform a thorough review of a patient's clinical and treatment history for interpreting the results of syphilis serology. PMID- 26560545 TI - Veterinary Students' Recollection Methods for Surgical Procedures: A Qualitative Study. AB - When veterinary students face their first live animal surgeries, their level of anxiety is generally high and this can affect their ability to recall the procedure they are about to undertake. Multimodal teaching methods have previously been shown to enhance learning and facilitate recall; however, student preferences for recollection methods when translating theory into practice have not been documented. The aim of this study was to investigate veterinary students' experience with recollection of a surgical procedure they were about to perform after using multiple methods for preparation. From a group of 171 veterinary students enrolled in a basic surgery course, 26 students were randomly selected to participate in semi-structured interviews. Results showed that 58% of the students used a visual, dynamic method of recollection, mentally visualizing the video they had watched as part of their multimodal preparation. A mental recipe was used by 15%, whereas 12% mentally visualized their own notes. The study provides new information regarding veterinary students' methods of recollection of surgical procedures and indicates that in Danish veterinary students, a visual dynamic method is the most commonly used. This is relevant information in the current educational situation, which uses an array of educational tools, and it stresses the importance of supporting the traditional surgical teaching methods with high-quality instructional videos. PMID- 26560546 TI - Development and Use of an Interactive Computerized Dog Model to Evaluate Cranial Nerve Knowledge in Veterinary Students. AB - In veterinary medicine, the cognitive skills necessary to interpret neurological disorders from text-based case descriptions may not translate into the diagnostic capabilities required for clinical neurological patients. As live animals exhibiting certain specific neurological disorders are infrequent during a student's exposure to clinics, students may graduate without the experience necessary to make an accurate diagnosis in the field. To address this, we have developed a computerized simulated dog head that can exhibit cranial nerve dysfunctions and respond to specific testing procedures in a clinically accurate manner. To evaluate whether this type of model could add value to traditional student assessments, we created a multiple-choice quiz system with three types of questions: standard text-based cases, videos of an expert performing an examination of the simulated dog, and an interactive version requiring the student to perform an appropriate examination of the simulated dog to uncover the lesion localization. In an experiment conducted with 97 freshman veterinary students who had recently been taught cranial nerve anatomy and function, we found that examination performance decreased with the need for interactivity compared to memorization of fact, while satisfaction increased. Students were less likely to identify the correct disorder when they had to conduct the examination of the virtual dog themselves, revealing an inadequacy in traditional neuroanatomical teaching. However, students overwhelmingly supported the use of interactive question for assessment. Interestingly, performance on text-based questions did not correlate significantly with interactive or video questions. The results have implications for veterinary teaching and assessment within the classroom and in clinical environments. PMID- 26560544 TI - Epidemiology Analysis of Streptococcus pyogenes in a Hospital in Southern Taiwan by Use of the Updated emm Cluster Typing System. AB - emm typing is the most widely used molecular typing method for the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). emm typing is based on a small variable region of the emm gene; however, the emm cluster typing system defines GAS types according to the nearly complete sequence of the emm gene. Therefore, emm cluster typing is considered to provide more information regarding the functional and structural properties of M proteins in different emm types of GAS. In the present study, 677 isolates collected between 1994 and 2008 in a hospital in southern Taiwan were analyzed by the emm cluster typing system. emm clusters A-C4, E1, E6, and A-C3 were the most prevalent emm cluster types and accounted for 67.4% of total isolates. emm clusters A-C4 and E1 were associated with noninvasive diseases, whereas E6 was significantly associated with both invasive and noninvasive manifestations. In addition, emm clusters D4, E2, and E3 were significantly associated with invasive manifestations. Furthermore, we found that the functional properties of M protein, including low fibrinogen-binding and high IgG-binding activities, were correlated significantly with invasive manifestations. In summary, the present study provides updated epidemiological information on GAS emm cluster types in southern Taiwan. PMID- 26560547 TI - Understanding Reliability: A Review for Veterinary Educators. AB - Veterinary medical faculty and administrators routinely administer student assessments and conduct surveys to make decisions regarding student performance and to assess their courses/curricula. The decisions that are made are a result of the scores generated. However, how reliable are the scores and how confident can we be about these decisions? Reliability is one of the hallmarks of validity evidence, but what does this mean and what affects the reliability of scores? The purpose of this article is to provide veterinary medical educators and administrators with fundamental information regarding the concept of reliability. Specifically, we review what sources of error reduce the reliability of scores and we describe the different types of reliability coefficients that are reported. PMID- 26560548 TI - Collaborative Testing in Practical Laboratories: An Effective Teaching-Learning Method in Histology. AB - This article presents an experimental teaching and learning program used in histology with first-year students in the second term in the Faculty of Biology at Huanghuai University, China. Eighty-six students were divided randomly into two groups (n=43 per group). Tests were conducted at the end of each practical laboratory (10 laboratories in total) in which collaborative testing was used in the experimental group and traditional testing in the control group. To assess achievement, a final examination in histology was carried out at the end of the course. To determine students' attitude to the teaching styles, a questionnaire survey was conducted at the end of the term. Results showed that students preferred the collaborative testing format. In the experimental group, students' scores were significantly higher than those of students in the control group in final examinations. These findings indicate that collaborative testing enhances student learning and understanding of the material taught, and suggest that collaborative testing is an effective teaching-learning method in histology. PMID- 26560549 TI - Clinical Practice of Epidural Puncture in Dogs and Cats Assisted by a Commercial Acoustic Puncture Assist Device-Epidural Locator: Preliminary Results. AB - The objective of this study was to compare an Acoustic Puncture Assist Device Epidural Locator (APAD-EL) with the "pop sensation" (POP) and "lack of resistance" (LOR) commonly used to confirm penetration of the ligamentum flavum and to ensure correct epidural placement in dogs and cats. We recruited 38 dogs and cats undergoing surgery and receiving epidural analgesia. Two anesthetists performed epidural puncture using the POP and LOR signs. Simultaneously, APAD-EL was used to collect visual and acoustic confirmation during advancement and placement of the needle tip for post hoc evaluation. A positive APAD-EL sign consists of a sudden pressure drop at the needle tip visible on a display and a concomitant pitch change of an acoustic signal. Failure to record a sudden pressure drop is considered a negative APAD sign. Descriptive statistics were used. In 32 patients with positive POP and LOR, the APAD was also positive. In one patient, POP was positive with a negative LOR and APAD result. Five patients had negative POP but positive LOR. Four patients had APAD positive and one (a dog) APAD negative. The study results showed that the APAD-EL information supports the subjective signs of correct needle placement suggested by positive POP and LOR experienced by trained anesthetists. The technique can be useful to assist difficult epidural puncture and as a training and teaching tool. PMID- 26560550 TI - Rater Errors in Clinical Performance Assessments. AB - Rater errors are some of the most significant validity threats to any performance assessment. Veterinary medical education routinely uses raters to assess student performance in a variety of scenarios (e.g., clinical assessments, OSCEs, etc.). The purpose of this "teaching tip" is to introduce veterinary medical educators to the notion of rater error, identify a list of common rater errors, and discuss how these errors can be addressed and minimized so as to produce accurate and defensible measures of student performance. PMID- 26560551 TI - Biochemical Pharmacology of the Sigma-1 Receptor. AB - The sigma-1 receptor (S1R) is a 223 amino acid two transmembrane (TM) pass protein. It is a non-ATP-binding nonglycosylated ligand-regulated molecular chaperone of unknown three-dimensional structure. The S1R is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes with broad functions that regulate cellular calcium homeostasis and reduce oxidative stress. Several multitasking functions of the S1R are underwritten by chaperone-mediated direct (and indirect) interactions with ion channels, G protein coupled receptors and cell-signaling molecules involved in the regulation of cell growth. The S1R is a promising drug target for the treatment of several neurodegenerative diseases related to cellular stress. In vitro and in vivo functional and molecular characteristics of the S1R and its interactions with endogenous and synthetic small molecules have been discovered by the use of pharmacologic, biochemical, biophysical, and molecular biology approaches. The S1R exists in monomer, dimer, tetramer, hexamer/octamer, and higher oligomeric forms that may be important determinants in defining the pharmacology and mechanism(s) of action of the S1R. A canonical GXXXG in putative TM2 is important for S1R oligomerization. The ligand-binding regions of S1R have been identified and include portions of TM2 and the TM proximal regions of the C terminus. Some client protein chaperone functions and interactions with the cochaperone 78-kDa glucose-regulated protein (binding immunoglobulin protein) involve the C terminus. Based on its biochemical features and mechanisms of chaperone action the possibility that the S1R is a member of the small heat shock protein family is discussed. PMID- 26560552 TI - Effect of post-harvest treatments on the occurrence of ochratoxin A in raw cocoa beans. AB - Cocoa beans are the principal raw material for chocolate manufacture. Moulds have an important place in the change in the quality of cocoa beans due to their role in the production of free fatty acids and mycotoxins, namely ochratoxin A (OTA). This study investigated the impact of the key post-harvest treatments, namely the fermentation and drying methods on OTA contamination of raw cocoa beans. Analytical methods for OTA detection were based on solid-liquid extraction, clean up using an immunoaffinity column, and identification by reversed-phase HPLC with fluorescence detection. Of a total of 104 randomly selected cocoa samples analysed, 32% had OTA contents above 2 ug kg(-1). Cocoa sourced from pods in a bad state of health had a maximum OTA content of 39.2 ug kg(-1), while that obtained from healthy pods recorded 11.2 ug kg(-1). The production of OTA in cocoa beans increased according to the pod-opening delay and reached 39.2 ug kg( 1) after an opening delay of 7 days after harvest, while 6.1 and 11.2 ug kg(-1) were observed when pods were opened after 0 and 4 days. OTA production also seemed to depend considerably to the cocoa fermentation materials. When using plastic boxes for bean fermentation, the OTA production was enhanced and reached an average OTA content of about 4.9 ug kg(-1), while the raw cocoa treated in banana leaves and wooden boxes recorded 1.6 and 2.2 ug kg(-1) on average respectively. In parallel, the OTA production was not really influenced by either the mixing or the duration of the fermentation or the drying materials. PMID- 26560553 TI - Distinguishing high-flow from low-flow vascular malformations using maximum intensity projection images in dynamic magnetic resonance angiography - comparison to other MR-based techniques. AB - BACKGROUND: In addition to ultrasound, magnetic resonance imaging (MRI) is considered a suitable, non-invasive technique to assess the type and extent of vascular malformations. The distinction between low- and high-flow lesions is crucial because it determines appropriate patient treatment. PURPOSE: To distinguish high-flow from low-flow lesions on the basis of the enhancement pattern on MIP images acquired from dynamic time-resolved MR angiography (MRA) and compare it with previously described MR-based methods. MATERIAL AND METHODS: We examined 25 consecutive patients with previously diagnosed vascular malformations. Next, each malformation was classified as "high-flow" or "low flow" using the following criteria: (i) findings on T1-weighted (T1W) and T2 weighted (T2W) imaging (signal voids, signal intensity); (ii) the time interval between the start of arterial enhancement and the onset of lesion enhancement (artery-lesion time); (iii) the time of maximum lesion enhancement; and (iv) analysis of the slope of the enhancement curve. RESULTS: Of the 25 patients, seven had high-flow and 18 had low-flow malformations. Signal voids on spin-echo T1W images were observed only in four of seven high-flow malformations and in two of 18 low-flow malformations. Analysis of signal intensity on T2W images showed increased signal intensity in 17 of 18 low-flow malformations, and in two of seven high-flow lesions. Calculation of the artery-lesion time, maximum enhancement time, and slope revealed significant differences between the high- and low-flow groups. CONCLUSION: In conclusion, the slope of the enhancement curve appears to be useful in distinguishing between high- and low-flow vascular malformations. Standardization of MR image evaluation criteria is essential. PMID- 26560554 TI - [Reply to "Meningitis, lumbar puncture and procalcitonin"]. PMID- 26560555 TI - Free-space optical channel simulator for weak-turbulence conditions. AB - Free-space optical (FSO) communication may be severely influenced by the inevitable turbulence effect that results in channel gain fluctuations and fading. The objective of this paper is to provide a simple and effective simulator of the weak-turbulence FSO channel that emulates the influence of the temporal covariance effect. Specifically, the proposed model is based on lognormal distributed samples with a corresponding correlation time. The simulator is based on the solution of the first-order stochastic differential equation (SDE). The results of the provided SDE analysis reveal its efficacy for turbulent channel modeling. PMID- 26560556 TI - Simple method based on intensity measurements for characterization of aberrations from micro-optical components. AB - We report a simple method, based on intensity measurements, for the characterization of the wavefront and aberrations produced by micro-optical focusing elements. This method employs the setup presented earlier in [Opt. Express 22, 13202 (2014)] for measurements of the 3D point spread function, on which a basic phase-retrieval algorithm is applied. This combination allows for retrieval of the wavefront generated by the micro-optical element and, in addition, quantification of the optical aberrations through the wavefront decomposition with Zernike polynomials. The optical setup requires only an in motion imaging system. The technique, adapted for the optimization of micro optical component fabrication, is demonstrated by characterizing a planoconvex microlens. PMID- 26560557 TI - High-contrast filtering by multipass diffraction between paired volume Bragg gratings. AB - High-contrast filtering via multiple reflections between matched volume Bragg gratings (VBGs) is demonstrated. The use of multiple reflections serves to increase the suppression ratio of the out-of-band spectral content such that contributions of grating sidelobes can be mitigated. The result is a device that retains spectral and angular selectivity and diffracts light into a single order with high efficiency but reshapes the spectral/angular response to achieve higher signal-to-noise ratios. We demonstrate that multipass spectral filters can be recorded with extremely high suppression ratios using reflecting Bragg gratings (RBGs) in three different configurations. These filters demonstrate roll-offs of over 150 dB/nm. Similarly, we demonstrate angular filtering by multipass transmitting gratings. PMID- 26560558 TI - Three-dimensional reconstruction method for flame chemiluminescence distribution with complicated structure. AB - In this study, reconstruction of flame chemiluminescence distribution with complicated structure was numerically investigated and experimentally validated. The ill-conditioned equations were constructed using the quasi-Monte Carlo method and solved by an algebraic reconstruction technique, where the convergence criterion was the Euclidean norm of the dimensionless displacement vector. Results of a phantom study revealed that the number of camera angles is the main restriction on reconstruction accuracy, and increase of the flame's nonhomogeneity improves the sensibility of reconstruction accuracy to image resolution. Results of experimental reconstruction showed the CH* distribution in a Meker burner flame. This work provides a better understanding in how to establish experimental systems for complicated flame reconstruction. PMID- 26560559 TI - Assessment of the characterization of nonabsorbing nanoparticles in suspension from effective optical properties. AB - We analyze a method recently proposed to retrieve the size, refractive index, and concentration of particles in nonabsorbing nanofluids from measurements of the complex effective refractive index of two dilutions of the nanofluid [Opt. Lett.39, 559 (2014)]. The method uses simple formulas to retrieve the particles' parameters. First, we discuss precautions needed with the new method when inferring the refractive index of the particles from measurements of the imaginary part of the effective refractive index of two dilutions of the original nanofluid. Then we analyze the use of this methodology to obtain some average radius in the size of polydisperse suspensions and in the case of suspensions of weakly absorbing particles. We also perform an error analysis considering fixed errors in measurements and calculating the errors in the retrieved size, refractive index, and concentration of particles. Finally, we characterize experimentally nanofluids of polymeric particles fabricated of poly(methyl methacrylate) (PMMA) and polystyrene (PS) for which we achieved an uncertainty of 5*10(-3) and 1*10(-2) in the determination of the particle refractive index, respectively, and a precision better than 3% in the determination of their radii. PMID- 26560560 TI - Application of vector ray tracing to the computation of Mobius shifts for the primary and secondary rainbows. AB - The Mobius approximation for the primary rainbow and the Konnen approximation for the secondary rainbow have been modified to yield consistent predictions of the Mobius shift of the top and bottom rainbows, respectively. The applicability ranges of the Mobius and Konnen approximations are investigated by comparison to vector ray tracing (VRT) simulations. For the primary rainbow, these results indicate that the Mobius approximation is valid for spheroidal water droplets (m=1.333) in the range of aspect ratios 0.98<=a/c<=1.02. For the secondary rainbow, the Konnen approximation predicts the Mobius shift well for spheroidal water droplets within the range 0.99<=a/c<=1.01. For a spheroidal droplet with side-on incidence, the difference between the approximations and VRT simulations are discussed. Furthermore, the dependence of Mobius shifts on the relative refractive index of droplet is discussed. PMID- 26560561 TI - Flexible geometrical calibration for fringe-reflection optical three-dimensional shape measurement. AB - Accurate geometrical calibration is the basis of a fringe-reflection testing system, especially the calibration of reflection ray directions. However, such a calibration procedure is challenging because of two reasons: first of all, the common method of reflection ray directions calibration, which is based on the pinhole camera imaging model, fails in the presence of the pupil imaging aberration. What's more, although using a camera lens with an external stop in front can remove the pupil imaging aberration, it is difficult to achieve the exact geometrical measurement of the camera pinhole and the calibration of the reflection ray directions into the camera because of the low signal-to-noise ratio of images. In this paper, we introduce a new calibration method by finding the points on the liquid crystal display in front of the camera with different positions corresponding to the same camera pixels through correspondence matching. The calibration process and the results from the experiments on fringe reflection testing demonstrate that the calibration method presented in this paper is simple, practical, and flexible. PMID- 26560562 TI - Universal dispersion model for characterization of optical thin films over a wide spectral range: application to hafnia. AB - A dispersion model capable of expressing the dielectric response of a broad class of optical materials in a wide spectral range from far IR to vacuum UV is described in detail. The application of this universal dispersion model to a specific material is demonstrated using the ellipsometric and spectrophotometric characterization of a hafnia film prepared by vacuum evaporation on silicon substrate. The characterization utilizes simultaneous processing of data from multiple techniques and instruments covering the wide spectral range and includes the characterization of roughness, nonuniformity, transition layer, and native oxide layer on the back of the substrate. It is shown how the combination of measurements in light reflected from both sides of the sample and transmitted light allows the separation of weak absorption in films and substrates. This approach is particularly useful in the IR region where the absorption structures in films and substrates often overlap and a prior measurement of the bare substrate may be otherwise necessary for precise separation. Individual phenomena that contribute to the dielectric response, i.e., interband electronic transitions, electronic excitations involving the localized states, and phonon absorption, are discussed in detail. A quantitative analysis of absorption on localized states, permitting the separation of transitions between localized states from transitions between localized and extended states, is utilized to obtain estimates of the density of localized states and film stoichiometry. PMID- 26560563 TI - Properties of transmission and leaky modes in a plasmonic waveguide constructed by periodic subwavelength corrugated metallic wire with open hollow rings in THz regime. AB - In this paper, we propose a new metallic cylindrical antenna at terahertz frequencies using the concept of low-frequency spoof surface plasmon polaritons (SPPs). The antenna is developed by introducing an open hollow ring (OHR) in each unit cell of the conventional periodic subwavelength corrugated metallic wire (PSCMW). The new structure is referred to as the PSCMW-OHR. The dispersion properties of PSCMWs and PSCMW-OHRs, the near-field and far-field distributions, as well as the radiation efficiencies are numerically evaluated and compared. By analyzing the numerical results, we find that there are extra new propagation modes that exist in the annular groove of the PSCMW-OHR, aside from the normal transmission modes in the PSCMW. Moreover, the dispersion line of the new SPP mode exhibits a negative slope. Surprisingly and interestingly, after passing through the light line, the propagation gets into the radiation zone, where it becomes a leaky mode with a complex-valued propagation constant. We have found that the far-field radiation of propagation in the leaky mode can lead to frequency scanning effects with a scanning angle of 22 degrees , and the radiation efficiency can be increased to 90%, provided that the total number of the periodic unit cells is large enough. PMID- 26560564 TI - Study of the measurement for the diffusion coefficient by digital holographic interferometry. AB - In the measurement of the diffusion coefficient by digital holographic interferometry, the conformity between the experiment and the ideal physical model is lacking analysis. Two data processing methods are put forward to overcome this problem. By these methods, it is found that there is obvious asymmetry in the experiment and the asymmetry is becoming smaller with time. Besides, the initial time for diffusion cannot be treated as a constant throughout the whole experiment. This means that there is a difference between the experiment and the physical model. With these methods, the diffusion coefficient of KCl in water at 0.33 mol/L and 25 degrees C is measured. When the asymmetry is ignored, the result is 1.839*10(-9) m2/s, which is in good agreement with the data in the literature. Because the asymmetry is becoming smaller with time, the experimental data in the latter time period conforms to the ideal physical model. With this idea, a more accurate diffusion coefficient is 2.003*10(-9) m2/s, which is about 10% larger than the data in the literature. PMID- 26560565 TI - High-speed all-optical logic inverter based on stimulated Raman scattering in silicon nanocrystal. AB - In this paper, we propose a new device architecture for an all-optical logic inverter (NOT gate), which is cascadable with a similar device. The inverter is based on stimulated Raman scattering in silicon nanocrystal waveguides, which are embedded in a silicon photonic crystal structure. The Raman response function of silicon nanocrystal is evaluated to explore the transfer characteristic of the inverter. A maximum product criterion for the noise margin is taken to analyze the cascadability of the inverter. The time domain response of the inverter, which explores successful inversion operation at 100 Gb/s, is analyzed. Propagation delay of the inverter is on the order of 5 ps, which is less than the delay in most of the electronic logic families as of today. Overall dimension of the device is around 755 MUm *15 MUm, which ensures integration compatibility with the matured silicon industry. PMID- 26560566 TI - Thermally induced all-optical inverter and dynamic hysteresis loops in graphene oxide dispersions. AB - We experimentally study the temporal dynamics of amplitude-modulated laser beams propagating through a water dispersion of graphene oxide sheets in a fiber-to fiber U-bench. Nonlinear refraction induced in the sample by thermal effects leads to both phase reversing of the transmitted signals and dynamic hysteresis in the input-output power curves. A theoretical model including beam propagation and thermal lensing dynamics reproduces the experimental findings. PMID- 26560567 TI - Optimization of long-period grating-based refractive index sensor by bent-fiber interference. AB - In this paper, we propose and demonstrate a novel approach to enhance the refractive index (RI) sensitivity and eliminate the temperature cross-sensitivity of a long-period grating (LPG) -based refractive index sensor by bent-fiber interference. The approach is based on a hybrid structure composed of an LPG and a bent-fiber intermodal interferometer. The bent-fiber intermodal interferometer has a simple structure, which consists of a bare fiber semi-circular bending region with a 5 mm bending radius. As the RI increases, the resonance wavelength of the LPG moves toward a shorter wavelength, while the resonance wavelength of the bent-fiber intermodal interferometer shifts to a longer wavelength. The separation of two resonance dips increases with the RI; using two resonance dips allows us to measure an RI with a higher sensitivity than if we had only used one resonance dip. However, as the temperature increases, the separation of the two resonance dips is constant. This approach can effectively enhance the RI sensitivity and eliminate temperature cross-sensitivity. PMID- 26560568 TI - Effect of AO/UV/RD exposure on spaceborne diffusers: a comparative experiment. AB - The environmental measuring instrument (EMI) is a nadir-viewing wide-field imaging spectrometer, which adopts spaceborne diffusers in in-flight calibration systems, including an aluminum diffuser and a quartz volume diffuser. Spaceborne diffusers, are the key components of in-flight calibration systems, and are used to introduce sunlight into the EMI. Hemispheric reflectance and bidirectional reflectance distribution function were experimentally measured to analyze spaceborne diffuser performance. Radiation exposure experiments on atomic oxygen, UV, and radiation dose of the spaceborne diffusers were performed at ground level because the EMI works in low Earth orbit space environments. Effects of radiation exposure on spaceborne diffusers were discussed in detail. Protective methods were introduced to reduce the effects of the space environment, and an in-orbit monitoring method was also proposed. PMID- 26560569 TI - Polarization modulation of two-photon excited fluorescence in a V-shaped dipicolinate-triphenylamine compound. AB - Polarization modulation of two-photon excited fluorescence in a V-shaped dipicolinate-triphenylamine compound was investigated with 100 fs 800 nm laser pulses. The peak fluorescence intensity versus the input irradiance was measured to meet a square dependence, which offered evidence for two-photon excited fluorescence. The variations of the two-photon excited fluorescence intensity showed strong response to the different polarized incident lights and were tightly dependent on the linearly polarized component of the incident light. Furthermore, the polarization modulation efficiency of the two-photon excited fluorescence had an obvious concentration dependence when the concentration of solution was under 2.5*10(-4) mol/L. The enhancement of modulation efficiency was attributed to the concentration dependence of the two-photon absorption cross section. PMID- 26560570 TI - Efficient optical image amplifier using periodically poled lithium niobate. AB - An efficient optical image amplification scheme has been proposed and demonstrated using the quasi-phase-matched optical parametric amplifier. Pumped with the 152 MUJ per pulse pump laser at 532 nm, the input weak infrared image at 1064 nm with 3.5 pJ energy is amplified with a 55 dB optical gain using only a 3 mm long MgO-doped periodically poled lithium niobate (MgO:PPLN) crystal. A spatial resolution of 17 lines/mm on the surface of the PPLN crystal is obtained. Further numerical simulation indicates that our scheme enables efficient image enhancement with a long pulsed pumping source, such as nanosecond lasers. PMID- 26560571 TI - Multifunctional magneto-metasurface for terahertz one-way transmission and magnetic field sensing. AB - A magneto-metasurface is demonstrated for one-way transmission of terahertz (THz) waves and magnetic field sensing. Due to the magneto-optical effect and the asymmetric structure of the transmission system, magnetoplasmon mode splitting for forward and backward THz waves and one-way transmission has been observed in this magneto-metasurface. Significantly, the resonance of the magneto-metasurface has been found that can remain at 0.750 THz at a temperature of 218 K, performing as a stable isolator with an isolation of larger than 30 dB within a magnetic field disturbance from 0.23 to 0.35 T. Also, since the resonance of the magneto metasurface can be tuned by the different external magnetic fields at a temperature that is higher or lower than 218 K, the magneto-metasurface can work as a highly sensitive magnetic field sensor. The sensitivity of this device reaches S=513.05 GHz.T(-1) when T=230 K. This multifunctional magneto metasurface has broad potential in THz application systems. PMID- 26560572 TI - Smartphone-based colorimetric analysis for detection of saliva alcohol concentration. AB - A simple device and associated analytical methods are reported. We provide objective and accurate determination of saliva alcohol concentrations using smartphone-based colorimetric imaging. The device utilizes any smartphone with a miniature attachment that positions the sample and provides constant illumination for sample imaging. Analyses of histograms based on channel imaging of red-green blue (RGB) and hue-saturation-value (HSV) color space provide unambiguous determination of blood alcohol concentration from color changes on sample pads. A smartphone-based sample analysis by colorimetry was developed and tested with blind samples that matched with the training sets. This technology can be adapted to any smartphone and used to conduct color change assays. PMID- 26560573 TI - Demonstration of temperature imaging by H2O absorption spectroscopy using compressed sensing tomography. AB - This paper introduces temperature imaging by total-variation-based compressed sensing (CS) tomography of H2O vapor absorption spectroscopy. A controlled laboratory setup is used to generate a constant two-dimensional temperature distribution in air (a roughly Gaussian temperature profile with a central temperature of 677 K). A wavelength-tunable laser beam is directed through the known distribution; the beam is translated and rotated using motorized stages to acquire complete absorption spectra in the 1330-1365 nm range at each of 64 beam locations and 60 view angles. Temperature reconstructions are compared to independent thermocouple measurements. Although the distribution studied is approximately axisymmetric, axisymmetry is not assumed and simulations show similar performance for arbitrary temperature distributions. We study the measurement error as a function of number of beams and view angles used in reconstruction to gauge the potential for application of CS in practical test articles where optical access is limited. PMID- 26560574 TI - Microfabricated Otto chip device for surface plasmon resonance-based optical sensing. AB - Surface plasmon resonance (SPR) based sensors are usually designed using the Kretschmann prism coupling configuration in which an input beam couples with a surface plasmon through a thin metal film. This is generally preferred by sensor developers for building planar devices instead of the Otto prism coupling configuration, which, for efficient coupling, requires the metal surface to be maintained at a distance on the order of the wavelength from the input prism surface. In this paper, we report on the microfabrication and characterization of an Otto chip device, which is suitable for applications of the SPR effect in gas sensing and biosensing. PMID- 26560575 TI - Pareto optimality between width of central lobe and peak sidelobe intensity in the far-field pattern of lossless phase-only filters for enhancement of transverse resolution. AB - Resolution capability of an optical imaging system can be enhanced by reducing the width of the central lobe of the point spread function. Attempts to achieve the same by pupil plane filtering give rise to a concomitant increase in sidelobe intensity. The mutual exclusivity between these two objectives may be considered as a multiobjective optimization problem that does not have a unique solution; rather, a class of trade-off solutions called Pareto optimal solutions may be generated. Pareto fronts in the synthesis of lossless phase-only pupil plane filters to achieve superresolution with prespecified lower limits for the Strehl ratio are explored by using the particle swarm optimization technique. PMID- 26560576 TI - Three-dimensional quantitative phase imaging via tomographic deconvolution phase microscopy. AB - The field of three-dimensional quantitative phase imaging (3D QPI) is expanding rapidly with applications in biological, medical, and industrial research, development, diagnostics, and metrology. Much of this research has centered on developing optical diffraction tomography (ODT) for biomedical applications. In addition to technical difficulties associated with coherent noise, ODT is not congruous with optical microscopy utilizing partially coherent light, which is used in most biomedical laboratories. Thus, ODT solutions have, for the most part, been limited to customized optomechanical systems which would be relatively expensive to implement on a wide scale. In the present work, a new phase reconstruction method, called tomographic deconvolution phase microscopy (TDPM), is described which makes use of commercial microscopy hardware in realizing 3D QPI. TDPM is analogous to methods used in deconvolution microscopy which improve spatial resolution and 3D-localization accuracy of fluorescence micrographs by combining multiple through-focal scans which are deconvolved by the system point spread function. TDPM is based on the 3D weak object transfer function theory which is shown here to be capable of imaging "nonweak" phase objects with large phase excursions. TDPM requires no phase unwrapping and recovers the entire object spectrum via object rotation, mitigating the need to fill in the "missing cone" of spatial frequencies algorithmically as in limited-angle ODT. In the present work, TDPM is demonstrated using optical fibers, including single-mode, polarization-maintaining, and photonic-crystal fibers as well as an azimuthally varying CO2-laser-induced long-period fiber grating period as test phase objects. PMID- 26560577 TI - Radiative transfer model for contaminated rough slabs. AB - We present a semi-analytical model to simulate the bidirectional reflectance distribution function (BRDF) of a rough slab layer containing impurities. This model has been optimized for fast computation in order to analyze massive hyperspectral data by a Bayesian approach. We designed it for planetary surface ice studies but it could be used for other purposes. It estimates the bidirectional reflectance of a rough slab of material containing inclusions, overlaying an optically thick media (semi-infinite media or stratified media, for instance granular material). The inclusions are assumed to be close to spherical and constituted of any type of material other than the ice matrix. It can be any other type of ice, mineral, or even bubbles defined by their optical constants. We assume a low roughness and we consider the geometrical optics conditions. This model is thus applicable for inclusions larger than the considered wavelength. The scattering on the inclusions is assumed to be isotropic. This model has a fast computation implementation and thus is suitable for high-resolution hyperspectral data analysis. PMID- 26560578 TI - Toward the design of a motion-free tunable coupling module for varying spatial beam profiles: foundations of optimal coupling of a Gaussian mode into a fiber collimator with a dynamic two-lens system. AB - In this paper, we present analytical expressions for the coupling of the fundamental Gaussian mode into a fiber collimator (FC) using a two-lens system. For this two-lens system, we also derive the limiting condition imposed on the focal lengths of the two individual lenses and their mutual separation for near to-perfect mode coupling into the FC. Variations in the spatial mode profile of a Gaussian beam may occur due to various reasons. These include controlled changes in the beam profile inside mode-division multiplexed systems, and undesired spatial profile variations in beams that pass through turbulent media. The necessity of a dynamic mode-coupling module is dictated by the need to optimally couple Gaussian beams with dynamically changing spatial profiles. Using the analytical expressions derived for mode-coupling efficiency and the resulting lens separation condition that is imposed on a two-lens coupling system, we propose the design of a dynamic two-lens mode-coupling system with a pair of electronically controlled tunable lenses. The proposed dynamic coupling module is motion free and involves the movement of bulk components in order to achieve optimal coupling. The experimental results are also presented to verify the theoretical claims and the working principle of a two-lens mode-coupling system. The results of the experiments are discussed in detail and an excellent agreement is demonstrated between the proposed theoretical framework and the experimental results. PMID- 26560579 TI - In vivo assessment of wall strain in embryonic chick heart by spectral domain optical coherence tomography. AB - The ability to measure in vivo wall strain in embryonic hearts is important for fully understanding the mechanisms of cardiac development. Optical coherence tomography (OCT) is a powerful tool for the three-dimensional imaging of complex myocardial activities in early-stage embryonic hearts with high spatial and temporal resolutions. We describe a method to analyze periodic deformations of myocardial walls and evaluate in vivo myocardial wall strains with a high-speed spectral domain OCT system. We perform four-dimensional scanning on the outflow tract (OFT) of chick embryonic hearts and determine a special cross-section in which the OFT can be approximated as an annulus by analyzing Doppler blood-flow velocities. For each image acquired at the special cross-section, the annular myocardial wall is segmented with a semiautomatic boundary-detection algorithm, and the fluctuation myocardial wall thickness is calculated from the area and mean circumference of the myocardial wall. The experimental results shown with the embryonic chick hearts demonstrate that the proposed method is a useful tool for studying the biomechanical characteristics of embryonic hearts. PMID- 26560580 TI - Efficient internal and surface fingerprint extraction and blending using optical coherence tomography. AB - Optical coherence tomography provides a 3D representation of fingertip skin where surface and internal fingerprints are found. These fingerprints are topographically identical. However, the surface skin is prone to damage, distortion, and spoofing; and the internal fingerprint is difficult to access and extract. This research presents a novel scaling-resolution approach to fingerprint zone detection and extraction. Furthermore, a local-quality-based blending procedure is also proposed. The accuracy of the zone-detection algorithm is comparable to an earlier work, yielding a mean-squared error of 25.9 and structural similarity of 95.8% (compared to a ground-truth estimate). Blending the surface and internal fingerprints improved the National Institute of Science and Technology's Fingerprint Image Quality scores and the average maximum match scores (when matched against conventional surface counterparts). The fingerprint blending procedure was able to combine high-quality regions from both fingerprints, thus mitigating surface wrinkles and anomalous poor-quality regions. Furthermore, spoof detection via a surface-to-internal fingerprint comparison was proposed and tested. PMID- 26560581 TI - Common-mode rejection in Martin-Puplett spectrometers for astronomical observations at millimeter wavelengths. AB - The Martin-Puplett interferometer (MPI) is a differential Fourier transform spectrometer that measures the difference between spectral brightness at two input ports. This unique feature makes the MPI an optimal zero instrument, able to detect small brightness gradients embedded in a large common background. In this paper, we experimentally investigate the common-mode rejection achievable in the MPI at millimeter wavelengths, and discuss the use of the instrument to measure the spectrum of cosmic microwave background anisotropy. PMID- 26560582 TI - Computational imaging based on time-correlated single-photon-counting technique at low light level. AB - Imaging at low light levels has drawn much attention. In this paper, a method is experimentally demonstrated to realize computational imaging under weak illumination conditions. In our experiment, only one single-photon detector was used to capture the photons. With the time-correlated single-photon-counting technique, photons at a quite low level can be recorded and the time distribution histograms were constructed. The intensity of the light can be estimated from the histograms. The detection model was discussed, and clear images were obtained through a ghost-imaging algorithm. In addition, we propose a modified algorithm for the conventional ghost-imaging method that works more efficiently than the traditional ghost-imaging algorithm. Moreover, this method provides a solution for three-dimensional imaging combining with the time of flight of the photons. PMID- 26560583 TI - Measuring the four paraxial lens parameters using an autostigmatic microscope. AB - We describe a method of measuring the four paraxial lens parameters-the two radii, the center thickness, and the index-of a realistic-size positive lens using an autostigmatic microscope (ASM). The method is similar to measuring the radius of curvature of a concave mirror with an ASM but slightly more complex in that four characteristic distances must be measured to solve for the four unknown parameters. Once the four distances are measured, it is shown how to use an Excel spreadsheet and the add-in iterative "Solver" to find the four unknown parameters. Finding the paraxial lens parameters is useful for troubleshooting a lens assembly that does not perform as expected due to mislabeling, the incorrect glass type used, insertion into the assembly backward, or for finding a replacement glass type. PMID- 26560584 TI - Statistical model of the efficiency for spatial light coupling into a single-mode fiber in the presence of atmospheric turbulence. AB - The average efficiency of spatial light coupling into a single-mode optical fiber is widely used but cannot estimate the signal-to-noise ratio (SNR) and bit error rate (BER) in free-space optical communication. We provide a statistical model for coupling efficiency and derive the exact expression of the probability density function (PDF). The simulation results confirm that the model is reasonable in the condition of different turbulence intensities and wavefront compensation terms, which is also consistent with our outdoor experiment. We also estimate the average SNR and BER using the PDF. The model is quite useful in a satellite-to-ground laser communication downlink. PMID- 26560585 TI - Efficient and robust phase unwrapping algorithm based on unscented Kalman filter, the strategy of quantizing paths-guided map, and pixel classification strategy. AB - This paper presents an efficient and robust phase unwrapping algorithm which combines an unscented Kalman filter (UKF) with a strategy of quantizing a paths guided map and a pixel classification strategy based on phase quality information. The advantages of the proposed method depend on the following contributions: (1) the strategy of quantizing the paths-guided map can accelerate the process of searching unwrapping paths and greatly reducing time consumption on the unwrapping procedure; (2) the pixel classification strategy proposed by this paper can reduce the error propagation effect by decreasing the amounts of pixels with equal quantized paths-guided value in the process of unwrapping; and (3) the unscented Kalman filter enables simultaneous filtering and unwrapping without the information loss caused by linearization of a nonlinear model. In addition, a new paths-guided map derived from a phase quality map is inserted into the strategy of quantizing the paths-guided map to provide a more robust path of unwrapping, and then ensures better unwrapping results. Results obtained from synthetic data and real data show that the proposed method can efficiently obtain better solutions with respect to some of the most used algorithms. PMID- 26560586 TI - Laser reflection differential confocal large-radius measurement. AB - A laser reflection differential confocal large-radius measurement (RDCLRM) method is proposed to meet the requirements of high-precision measurement for a large radius of curvature (ROC). The RDCLRM identifies the converging point of the multiply reflected test beam by using the differential confocal focusing technology. It then measures the distance between the positions of the test lens corresponding to these converging points for different reflection times. Therefore, a precise and high-efficiency measurement of a large ROC is achieved with a shorter measurement lightpath. The theoretical analyses and preliminary experimental results indicate that RDCLRM has a relative expanded uncertainty of better than 0.005% (k=2). PMID- 26560587 TI - Application of point diffraction interferometry for measuring angular displacement to a sensitivity of 0.01 arcsec. AB - The use of point diffraction interferometry is reported for measuring minutes, on the order of 0.01 arcsec angular movements. The algorithm for determining the angular displacement by the dynamics of the interference pattern is described. We also demonstrate results for applying this method to the study of the linearity and hysteresis of the angular shift of the platform, controlled by piezo actuators, which are designed for angular adjustment of the mirror of a solar extreme-ultraviolet telescope. PMID- 26560588 TI - Displacement measurement using a laser feedback grating interferometer. AB - A novel laser feedback grating interferometer (LFGI) with a phase-generated carrier demodulation technique is proposed in this paper. Laser feedback grating interference occurs when light emitted from a laser is diffracted by the double diffraction system and re-enters the laser active cavity, thus generating a modulation of the lasing field. In order to improve the displacement measurement resolution, phase modulation is introduced by an electro-optic modulator in the external cavity of the LFGI. Detection of the displacement can be easily achieved by the time-domain orthogonal demodulation, which does not involve any complicated calculation and is insensitive to the sampling error. Experimental results show that the proposed system has a general nanometer-level resolution. It provides a potential displacement sensor with high resolution, simple mechanical structure, and good reliability. PMID- 26560589 TI - Near-field observation of surface plasmon polaritons launched by V-shaped nanorods on a gold surface. AB - By scanning near-field optical microscopy, we study the propagation of surface waves created by V-shaped nanorods deposited on a gold thin film. The nanorods launch surface plasmon polaritons that interfere with the incident light, producing interference patterns. The angle of the V-shaped rods varies from 110 degrees to 180 degrees (straight rod). We observe that the near-field distribution strongly depends on the angle of the V. For angles close to straight rods, a hot spot is visible, whereas for a narrower angle, the surface plasmon waves are launched in specific directions. The experimental results are in good qualitative agreement with numerical simulations performed with a simple analytical model that considers the rods as a sum of isolated surface plasmon sources. PMID- 26560590 TI - Radiometric calibration of the Visible Infrared Imaging Radiometer Suite reflective solar bands with robust characterizations and hybrid calibration coefficients. AB - The Visible Infrared Imaging Radiometer Suite (VIIRS) is now entering its fourth year of in-orbit global environmental observation and is producing a wide range of scientific output. The ocean color products in particular require a level of accuracy from the reflective solar bands (RSBs) that is a magnitude higher than the specification. In this work, we present an updated and completed core calibration pipeline that achieves the best sensor data records (SDR) to date and helps the ocean color products to reach maturity. We review the core calibration methodology of the RSBs and describe each essential input, including the solar diffuser stability monitor, the solar diffuser (SD), and lunar calibrations. Their associated issues, along with the successful mitigation and improved results, are described and presented. In particular, we illuminate the inaccuracy suffered due to the evolving angular dependence in the degradation of the on board SD that impacts the heart of the RSB calibration, but also show that lunar based calibration instead provides the correct long-term baseline for the successful restoration of the core methodology. The new look-up tables, which combine the coefficients from the SD-based and lunar-based calibrations, produce the optimal result, with an estimated accuracy of ~0.2%. This hybrid approach highlights significant progress in the VIIRS RSB calibration and marks a completion of the core calibration result upon which other physical impacts or scientific issues can then be more accurately examined. We demonstrate the significant improvement and its impact on the ocean color products by comparing the current official output to the newly generated result. Lastly, we point out that this hybrid calibration coefficients scheme is made possible by a VIIRS design and layout change over its predecessor, the Moderate Resolution Imaging Spectroradiometer, that allows both the SD and the moon to be viewed by the RSB at the same angle of incidence. Thus, this design element warrants serious consideration for other satellite sensors utilizing a similar calibration methodology. PMID- 26560591 TI - Comprehensive simulation platform for a metamaterial imaging system. AB - Recently, a frequency-diverse, metamaterial-based aperture has been introduced in the context of microwave and millimeter wave imaging. The generic form of the aperture is that of a parallel plate waveguide, in which complementary metamaterial elements patterned into the upper plate couple energy from the waveguide mode to the scene. To reliably predict the imaging performance of such an aperture prior to fabrication and experiments, it is necessary to have an accurate forward model that predicts radiation from the aperture, a model for scattering from an arbitrary target in the scene, and a set of image reconstruction approaches that allow scene estimation from an arbitrary set of measurements. Here, we introduce a forward model in which the metamaterial elements are approximated as polarizable magnetic dipoles, excited by the fields propagating within the waveguide. The dipoles used in the model can have arbitrarily assigned polarizability characteristics. Alternatively, fields measured from actual metamaterial samples can be decomposed into a set of effective dipole radiators, allowing the performance of actual samples to be quantitatively modeled and compared with simulated apertures. To confirm the validity of our model, we simulate measurements and scene reconstructions with a virtual multiaperture imaging system operating in the K-band spectrum (18-26.5 GHz) and compare its performance with an experimental system. PMID- 26560592 TI - Experimental and theoretical investigation on passively Q-switched laser action in c-cut Nd:MgO:LiNbO3. AB - The performance of a diode-pumped c-cut Nd:MgO:LiNbO3 laser at 1093 nm was demonstrated. Under an absorbed pump power of 7.450 W, a maximum continuous wave output power of 1.570 W was obtained, corresponding to a slope efficiency of 26.0%. For passive Q-switching operation, 24 ns pulses were observed with a repetition rate of 17.1 kHz, resulting in a peak power of 1357 W. The experimental results were theoretically analyzed by a rate equation model, in which the Gaussian spatial distribution of the intracavity photon density was taken into account. PMID- 26560593 TI - Giant circular dichroism induced by silver nanocuboid heterodimers. AB - Metallic nanocuboid heterodimers are proposed to generate a giant circular dichroism (CD) effect. Two cuboids in the heterodimers have different heights. The dipole and quadrupole charge oscillation modes in the cuboids occur under left- and right-handed circular polarizations. The height difference generates phase difference between charge oscillations in the two cuboids. The two charge oscillations and the phase difference between them are consistent with the Born Kuhn model for the CD effect. The CD effect of the nanocuboid heterodimers can be tuned by changing the structural parameters of the nanocuboid heterodimers, especially the height difference between two cuboids. The results of this research are not only useful for designing plasmonic structures to generate the CD effect but also for understanding the physical mechanisms of the CD effect. PMID- 26560594 TI - Composite method for precise freeform optical beam shaping. AB - We present a composite freeform surface construction method for creating a high accuracy irradiance distribution from a given incident beam under the influence of diffraction. The main idea is that we first determine a fully continuous freeform surface estimate by solving a standard Monge-Ampere equation and then refine it using an iterative Fourier-transform algorithm associated with over compensation. Although this method can only be implemented in the paraxial approximation, it can significantly simplify the design and is applicable to many examples that fulfill this restriction. The resulting optical surface, unwrapped from the final phase, is an unusual discontinuous freeform surface that can produce very promising performances in terms of surface roughness and irradiance accuracy. PMID- 26560595 TI - Peer Review Week: editorial. AB - Editor-in-Chief Ron Driggers discusses Peer Review Week. PMID- 26560596 TI - Gain and loss as a function of current density and temperature in interband cascade lasers. AB - We characterize the internal efficiency, internal loss, and optical gain versus current density in 7-stage interband cascade lasers operating at lambda=3.1 and 3.45 MUm using a cavity-length study of the external differential quantum efficiency (EDQE) and threshold current density at temperatures between 300 and 345 K. We find that the pronounced efficiency droop of the EDQE at high current densities is primarily due to an increase in the internal loss rather than a reduction in the internal efficiency. On the other hand, if the current density J is fixed, the temperature variation of the EDQE at that J is due primarily to a decrease of the internal efficiency. The gain versus current density is fit well by a logarithmic relationship, although the magnitude of the experimental gain is >20% below the theoretical estimate. PMID- 26560597 TI - High-energy krypton fluoride lasers for inertial fusion. AB - Laser fusion researchers have realized since the 1970s that the deep UV light from excimer lasers would be an advantage as a driver for robust high-performance capsule implosions for inertial confinement fusion (ICF). Most of this research has centered on the krypton-fluoride (KrF) laser. In this article we review the advantages of the KrF laser for direct-drive ICF, the history of high-energy KrF laser development, and the present state of the art and describe a development path to the performance needed for laser fusion and its energy application. We include descriptions of the architecture and performance of the multi-kilojoule Nike KrF laser-target facility and the 700 J Electra high-repetition-rate KrF laser that were developed at the U.S. Naval Research Laboratory. Nike and Electra are the most advanced KrF lasers for inertial fusion research and energy applications. PMID- 26560598 TI - Ultrafast Z-scan measurements of nonlinear optical constants of window materials at 772, 1030, and 1550 nm. AB - Femtosecond Z-scan measurements have been performed on six window materials at 772, 1030, and 1550 nm. Measurements of the nonlinear refractive index are presented for reference materials, fused silica and BK7 and four near-infrared window materials, multispectral ZnS (CLEARTRAN), aluminum oxynitride (AlON), spinel (MgAl2O4) ceramic, and barium gallogermanate (BGG) glass. PMID- 26560599 TI - Infrared photothermal imaging spectroscopy for detection of trace explosives on surfaces. AB - We are developing a technique for the standoff detection of trace explosives on relevant substrate surfaces using photothermal infrared (IR) imaging spectroscopy (PT-IRIS). This approach leverages one or more compact IR quantum cascade lasers, which are tuned to strong absorption bands in the analytes and directed to illuminate an area on a surface of interest. An IR focal plane array is used to image the surface and detect increases in thermal emission upon laser illumination. The PT-IRIS signal is processed as a hyperspectral image cube comprised of spatial, spectral, and temporal dimensions as vectors within a detection algorithm. The ability to detect trace analytes at standoff on relevant substrates is critical for security applications but is complicated by the optical and thermal analyte/substrate interactions. This manuscript describes a series of PT-IRIS experimental results and analysis for traces of RDX, TNT, ammonium nitrate, and sucrose on steel, polyethylene, glass, and painted steel panels. We demonstrate detection at surface mass loadings comparable with fingerprint depositions ( 10MUg/cm2 to 100MUg/cm2) from an area corresponding to a single pixel within the thermal image. PMID- 26560600 TI - Refractive index measurements of poly(methyl methacrylate) (PMMA) from 0.4-1.6 MUm. AB - Using a transmission-spectrum-based method, the refractive index of a 50 MUm thick sample of poly(methyl methacrylate) (PMMA) was measured as a function of wavelength. To mitigate the effects of nonplane-parallel surfaces, the sample was measured at 16 different locations. The technique resulted in the measurement of index at several thousand independent wavelengths from 0.42 to 1.62 MUm, with a relative RMS accuracy <0.5*10(-4) and absolute accuracy <2*10(-4). PMID- 26560601 TI - Simulation of free-space optical guiding structure based on colliding gas flows. AB - Preformed plasma channels with parabolic radial density profiles enable the extended and stable optical guiding of high-intensity laser pulses. High-voltage discharge capillaries, commonly used for channel formation, have limited guiding length and opaque walls, complicating the diagnosis of the plasma within. This paper proposes a free-space gas channel produced by the collision of several gas flows. The collision of the gas flows forms an on-axis density depression surrounded by higher density walls. By offsetting the flows, we demonstrated the creation of what we believe is a novel vortex structure that exhibits a long lived parabolic density profile. Once ionized, the resulting plasma density profile has a near-parabolic dependence appropriate for guiding. We then performed detailed two-dimensional (2D) fluid dynamics simulations to examine the properties and stability of the guiding structure. PMID- 26560602 TI - Imaging with multi-spectral mosaic-array cameras. AB - The emerging class of multi-spectral mosaic-array cameras combines opportunities of spectral data processing and full-motion video color display. We explore capabilities of such sensors and propose the novel demosaicking algorithm capable of enhancing resolution of equally sampled multi-spectral mosaic imagery. We present experimental results of the proposed processing using the imagery acquired with a nine-band short-wave infrared mosaic-array camera. PMID- 26560603 TI - Spatial heterodyne spectroscopy at the Naval Research Laboratory. AB - Spatial heterodyne spectroscopy (SHS) is based on traditional Michelson interferometry. However, instead of employing retro-reflectors in the interferometer arms, one or both of which are moving, it uses fixed, tilted diffraction gratings and an imaging detector to spatially sample the optical path differences. This concept allows high-resolution, high-throughput spectroscopy without moving interferometer parts, particularly suitable for problems that require compact, robust instrumentation. Here, we briefly review about 20 years of ground- and space-based SHS work performed at the U.S. Naval Research Laboratory (NRL), which started with a visit by Prof. Fred Roesler to NRL in 1993. PMID- 26560604 TI - Suspended photonic waveguide devices. AB - This article describes recent research at the U.S. Naval Research Laboratory that focuses on the use of micro- and nanomachining techniques for photonic waveguide devices. By selectively etching a sacrificial layer that the waveguide core is supported by, in whole or in part, the waveguide obtains enhanced properties and functionality, such as mechanical flexibility, index contrast, birefringence, and evanescent field depth. We describe how these properties enable unique waveguide applications in areas such as cavity optomechanics, displacement sensing, electro optics, and nonlinear optics. PMID- 26560605 TI - Power photodiodes for high dynamic range photonic links. AB - High-power photodiode applications for multioctave high dynamic range links are presented. A review of modulator and photodiode distortion analysis is given as well as an introduction to polarization-dependent loss distortion as it pertains to such systems. A new analysis of the photodiode distortion contributed degradation of spurious free dynamic range (SFDR) is developed. Experimental data covers high-power photodiodes for zero-bias high dynamic range links, showing significant improvement in SFDR. A link is presented showing the degradation of link performance when polarization-dependent loss is added into the system. A summary of state-of-the-art device performance is covered as well as the outlook on future applications for power photodiodes in analog photonic links requiring high SFDR. PMID- 26560606 TI - Optical measurements from single levitated particles using a linear electrodynamic quadrupole trap. AB - We have recently made advancements in a linear electrodynamic quadrupole (LEQ) device for capturing and levitating either single or multiple micro-particles that provides significant improvements in capture efficiency, reliability, and optical measurement access. We have used our LEQ to trap particles ranging from 30 to less than 0.5 MUm in size and provide a controlled environment to study particle physical/chemical dependencies on temperature, relative humidity, and gas constituents. To demonstrate this approach, we present data and analysis of liquid-droplet evaporation rates for two materials: glycerol and dibutyl sebacate. Droplet size was monitored as a function of time by two independent optical methods: direct imaging and fixed-angle light scattering. This new approach provides a means to rapidly characterize a wide range of aerosol particle properties and a platform for development of new aerosol optical diagnostic measurements. PMID- 26560607 TI - InAlAs/InGaAs avalanche photodiode arrays for free space optical communication. AB - In free space optical communication, photodetectors serve not only as communications receivers but also as position sensitive detectors (PSDs) for pointing, tracking, and stabilization. Typically, two separate detectors are utilized to perform these tasks, but recent advances in the fabrication and development of large-area, low-noise avalanche photodiode (APD) arrays have enabled these devices to be used both as PSDs and as communications receivers. This combined functionality allows for more flexibility and simplicity in optical system design without sacrificing the sensitivity and bandwidth performance of smaller, single-element data receivers. This work presents the development of APD arrays rated for bandwidths beyond 1 GHz with measured carrier ionization ratios of approximately 0.2 at moderate APD gains. We discuss the fabrication and characterization of three types of APD arrays along with their performance as high-speed photodetectors. PMID- 26560608 TI - Free-space optical communications research and demonstrations at the U.S. Naval Research Laboratory. AB - Free-space optical communication can allow high-bandwidth data links that are hard to detect, intercept, or jam. This makes them attractive for many applications. However, these links also require very accurate pointing, and their availability is affected by weather. These challenges have limited the deployment of free-space optical systems. The U.S. Naval Research Laboratory has, for the last 15 years, engaged in research into atmospheric propagation and photonic components with a goal of characterizing and overcoming these limitations. In addition several demonstrations of free-space optical links in real-world Navy applications have been conducted. This paper reviews this work and the principles guiding it. PMID- 26560609 TI - High-power lasers for directed-energy applications. AB - In this article, we review and discuss the research programs at the Naval Research Laboratory (NRL) on high-power lasers for directed-energy (DE) applications in the atmosphere. Physical processes affecting propagation include absorption/scattering, turbulence, and thermal blooming. The power levels needed for DE applications require combining a number of lasers. In atmospheric turbulence, there is a maximum intensity that can be placed on a target that is independent of the initial beam spot size and laser beam quality. By combining a number of kW-class fiber lasers, scientists at the NRL have successfully demonstrated high-power laser propagation in a turbulent atmosphere and wireless recharging. In the NRL experiments, four incoherently combined fiber lasers having a total power of 5 kW were propagated to a target 3.2 km away. These successful high-power experiments in a realistic atmosphere formed the basis of the Navy's Laser Weapon System. We compare the propagation characteristics of coherently and incoherently combined beams without adaptive optics. There is little difference in the energy on target between coherently and incoherently combined laser beams for multi-km propagation ranges and moderate to high levels of turbulence. Unlike incoherent combining, coherent combining places severe constraints on the individual lasers. These include the requirement of narrow power spectral linewidths in order to have long coherence times as well as polarization alignment of all the lasers. These requirements are extremely difficult for high-power lasers. PMID- 26560611 TI - Ultraviolet and extreme ultraviolet spectroscopy of the solar corona at the Naval Research Laboratory. AB - We review the history of ultraviolet and extreme ultraviolet spectroscopy with a specific focus on such activities at the Naval Research Laboratory and on studies of the extended solar corona and solar-wind source regions. We describe the problem of forecasting solar energetic particle events and discuss an observational technique designed to solve this problem by detecting supra-thermal seed particles as extended wings on spectral lines. Such seed particles are believed to be a necessary prerequisite for particle acceleration by heliospheric shock waves driven by a coronal mass ejection. PMID- 26560610 TI - Overview of transparent optical ceramics for high-energy lasers at NRL. AB - In this review, we present our recent research progress at the Naval Research Laboratory in the development of highly transparent and rugged ceramic window materials such as MgAl2O4 spinel and beta-SiC; high-power solid-state laser gain materials based on sesquioxide such as Yb(3+):Y2O3, Yb(3+):Lu2O3, and Ho(3+):Lu2O3; and composite ceramics in the application for high-energy lasers. Various powder synthesis/purification methods and powder post-process techniques necessary to create high-purity powders are described. Ceramic fabrication processes and chemical, morphological, and optical properties of the ceramics developed at the Naval Research Laboratory (NRL) are highlighted. We also report high-efficiency lasing from a hot-pressed rare-earth sesquioxide single layer and composite ceramics made from coprecipitated powder. PMID- 26560612 TI - Using a multiwavelength LiDAR for improved remote sensing of natural waters. AB - This paper describes research to characterize the benefits of a multiwavelength oceanographic LiDAR for various water types. Field measurements were conducted to establish endmembers representative of both typical and extremely challenging natural conditions. Laboratory tests were performed using a prototype multiwavelength LiDAR in water tanks with optical conditions simulating both sediment-laden and biologically rich water types. LiDAR models were used to simulate the LiDAR signal from both field and laboratory experiments. Our measurements and models show that using a laser wavelength of 470-490 nm in the open ocean leads to an improvement factor of 1.50-1.75 compared to a 532 nm system. In more turbid areas using a laser wavelength of 560-580 nm leads to an improvement factor of 1.25. We conclude by demonstrating how using multiple LiDAR wavelengths can help detect and characterize constituents in the water column. PMID- 26560613 TI - Wavelength dependence of the bidirectional reflectance distribution function (BRDF) of beach sands. AB - The wavelength dependence of the dominant directional reflective properties of beach sands was demonstrated using principal component analysis and the related correlation matrix. In general, we found that the hyperspectral bidirectional reflectance distribution function (BRDF) of beach sands has weak wavelength dependence. Its BRDF varies slightly in three broad wavelength regions. The variations are more evident in surfaces of greater visual roughness than in smooth surfaces. The weak wavelength dependence of the BRDF of beach sand can be captured using three broad wavelength regions instead of hundreds of individual wavelengths. PMID- 26560614 TI - Review of infrared fiber-based components. AB - The infrared range of the optical spectrum is attractive for its use in sensing, surveillance, and material characterization. The increasing availability of compact laser sources and detectors in the infrared range stands in contrast with the limited development of optical components for this optical range. We highlight developments of infrared components with a particular focus on fiber based components for compact optical devices and systems. PMID- 26560615 TI - Airborne system for multispectral, multiangle polarimetric imaging. AB - In this paper, we describe the design, fabrication, calibration, and deployment of an airborne multispectral polarimetric imager. The motivation for the development of this instrument was to explore its ability to provide information about water constituents, such as particle size and type. The instrument is based on four 16 MP cameras and uses wire grid polarizers (aligned at 0 degrees , 45 degrees , 90 degrees , and 135 degrees ) to provide the separation of the polarization states. A five-position filter wheel provides for four narrow-band spectral filters (435, 550, 625, and 750 nm) and one blocked position for dark level measurements. When flown, the instrument is mounted on a programmable stage that provides control of the view angles. View angles that range to +/-65 degrees from the nadir have been used. Data processing provides a measure of the polarimetric signature as a function of both the view zenith and view azimuth angles. As a validation of our initial results, we compare our measurements, over water, with the output of a Monte Carlo code, both of which show neutral points off the principle plane. The locations of the calculated and measured neutral points are compared. The random error level in the measured degree of linear polarization (8% at 435) is shown to be better than 0.25%. PMID- 26560616 TI - Optics research at the U.S. Naval Research Laboratory. AB - The Naval Research Laboratory (NRL) was established in Washington, DC in 1923 and is the corporate laboratory for the U.S. Navy and Marine Corps. Today NRL is a world-class research institution conducting a broad program of research and development (R&D), including many areas of optical science and technology. NRL is conducting cutting-edge R&D programs to explore new scientific areas to enable unprecedented Navy capabilities as well as improving current technologies to increase the effectiveness of Navy and other Department of Defense systems. This paper provides a broad overview of many of NRL's achievements in optics. Some of the remaining articles in this feature issue will discuss NRL's most recent research in individual areas, while other articles will present more detailed historical perspectives of NRL's research concerning particular scientific topics. PMID- 26560617 TI - Theoretical foundations of NRL spectral target detection algorithms. AB - The principal spectral detection algorithms developed at the Naval Research Laboratory (NRL) over the past 20 years for use in operational systems are described. These include anomaly detectors, signature-based methods, and techniques for anomalous change detection. Newer derivations are provided that have motivated more recent work. Mathematical methods facilitating the use of forward models for the prediction of spectral signature statistics are described and a detection algorithm is derived for ocean surveillance that is based on principles of clairvoyant fusion. PMID- 26560618 TI - Recent white-light coronagraphs at the Naval Research Laboratory. AB - A white-light externally occulted coronagraph is a telescope designed to view the very faint emission of the solar corona in the region close to the sun. It uses the Lyot principle to mitigate the effects of diffraction. The first such telescope flew on a spacecraft in 1971 and showed the dynamic nature of the corona. Since that mission, six other such coronagraphic telescopes have been flown, whose designs evolved to meet the requirements of the mission. This article describes the latest two coronagraphs and compares their capabilities and their designs. PMID- 26560619 TI - Review of antireflective surface structures on laser optics and windows. AB - We present recent advancements in structured, antireflective surfaces on optics, including crystals for high-energy lasers as well as windows for the infrared wavelength region. These structured surfaces have been characterized and show high transmission and laser damage thresholds, making them attractive for these applications. We also present successful tests of windows with antireflective surfaces that were exposed to simulated harsh environments for the application of these laser systems. PMID- 26560620 TI - Microwave photonic delay line signal processing. AB - This paper provides a path for the design of state-of-the-art fiber-optic delay lines for signal processing. The theoretical forms for various radio-frequency system performance metrics are derived for four modulation types: X- and Z-cut Mach-Zehnder modulators, a phase modulator with asymmetric Mach-Zehnder interferometer, and a polarization modulator with control waveplate and polarizing beam splitter. Each modulation type is considered to cover the current and future needs for ideal system designs. System gain, compression point, and third-order output intercept point are derived from the transfer matrices for each modulation type. A discussion of optical amplifier placement and fiber effect mitigation is offered. The paper concludes by detailing two high performance delay lines, built for unique applications, that exhibit performance levels an order of magnitude better than commercial delay lines. This paper should serve as a guide to maximizing the performance of future systems and offer a look into current and future research being done to further improve photonics technologies. PMID- 26560621 TI - Characterization of the temporal phase fluctuations in a weak atmospheric turbulence regime as a random bit-stream generator. AB - This paper investigates the extent to which atmospheric turbulence can be exploited as a random bit generator. Atmospheric turbulence is considered an inherently random process due to the complex inhomogeneous system composition and its sensitivity to changes in pressure, temperature, humidity, and wind conditions. A self-calibrating Mach-Zehnder interferometer was used to collect phase fluctuations in the temporal domain introduced to an optical beam propagating through the atmosphere. The recorded phase fluctuations were converted into bit streams that were further analyzed in order to search for evidence of randomness. Empirical data and results that characterize the degree of randomness produced in the temporal phase component of an optical wave propagating through the atmosphere are presented. PMID- 26560622 TI - Some results from the exploration of the solar atmosphere with high-resolution x ray-EUV spectroscopy at the Naval Research Laboratory. AB - The Naval Research Laboratory has been one of the world leaders in high resolution UV-x-ray solar spectroscopy. Much has been learned about the morphology and physical conditions in the atmosphere from spectroscopic instrumentation flown on orbiting spacecraft. In this short summary I discuss the solar atmosphere and our current knowledge of it, and show some of the results obtained by spectroscopic investigations at the Naval Research Laboratory. PMID- 26560623 TI - Toward high throughput optical metamaterial assemblies. AB - Optical metamaterials have unique engineered optical properties. These properties arise from the careful organization of plasmonic elements. Transitioning these properties from laboratory experiments to functional materials may lead to disruptive technologies for controlling light. A significant issue impeding the realization of optical metamaterial devices is the need for robust and efficient assembly strategies to govern the order of the nanometer-sized elements while enabling macroscopic throughput. This mini-review critically highlights recent approaches and challenges in creating these artificial materials. As the ability to assemble optical metamaterials improves, new unforeseen opportunities may arise for revolutionary optical devices. PMID- 26560624 TI - Spatially modulated laser pulses for printing electronics. AB - The use of a digital micromirror device (DMD) in laser-induced forward transfer (LIFT) is reviewed. Combining this technique with high-viscosity donor ink (silver nanopaste) results in laser-printed features that are highly congruent in shape and size to the incident laser beam spatial profile. The DMD empowers LIFT to become a highly parallel, rapidly reconfigurable direct-write technology. By adapting half-toning techniques to the DMD bitmap image, the laser transfer threshold fluence for 10 MUm features can be reduced using an edge-enhanced beam profile. The integration of LIFT with this beam-shaping technique allows the printing of complex large-area patterns with a single laser pulse. PMID- 26560625 TI - Optimizing average power in low quantum defect lasers. AB - Waste heat generation is a generic problem in high-power solid-state laser systems. One way to reduce heat loading while improving efficiency is to reduce the laser's quantum defect. This paper presents a simple analysis of low quantum defect laser materials. In these laser materials, the effects of fluorescent cooling and weak loss processes should not be ignored. Simple expressions are developed for efficiency and heating in a steady-state purely radiative material. These expressions are then extended to include weak losses and fluorescence reabsorption. Evaluation of these relations using ytterbium-doped YAG is used to illustrate several optimization schemes and the impact of realistic losses. PMID- 26560626 TI - Coherent light transmission properties of commercial photonic crystal hollow core optical fiber. AB - Photonic crystal hollow core fiber (PC-HCF) has enabled many exciting new applications in nonlinear optics and spectroscopy. However, to date there has been less impact in coherent applications where preservation of optical phase over long fiber lengths is crucial. This paper presents characteristics of three commercially available PC-HCFs relevant to coherent applications including higher order mode analysis, birefringence and polarization-dependent loss, and their impact on coherent light transmission in PC-HCF. Multipath interference due to higher-order mode propagation and Fresnel reflection is shown to generate excess intensity noise in transmission, which can be suppressed by up to 20 dB through high frequency phase modulation of the source laser. To demonstrate the potential of PC-HCF in high performance sensing, a Mach-Zehnder interferometer (MZI) incorporating 10 m of PC-HCF in each arm is characterized and demonstrates a phase resolution (59*10(-9) rad/Hz(1/2) at 30 kHz) close to the shot noise limit, which is better than can be achieved in a MZI made with the same length of single mode solid core fiber because of the limit set by fundamental thermodynamic noise (74*10(-9) rad/Hz(1/2) at 30 kHz). PMID- 26560627 TI - Combining semiconductor quantum dots and bioscaffolds into nanoscale energy transfer devices. AB - Significant advances have been made in the development of nanoscale devices capable of exciton transport via Forster resonance energy transfer. Several requirements must be met for effective operation, including a reliable energy harvesting source along with highly organized, precisely placed energy relay elements. For the latter, biological scaffolds such as DNA provide a customizable, symmetric, and stable structure that can be site-specifically modified with organic fluorophores. Here, advancements in nanoscale energy transfer devices incorporating semiconductor nanocrystals and bioscaffolds are reviewed with discussion of biofunctionalization, linker chemistries, design considerations, and concluding with applications in light harvesting, multiplexed biosensing, and optical logic. PMID- 26560628 TI - Irradiance correlations in retro-reflected beams. AB - Communications links that utilize modulating retro-reflectors can make use of turbulence-induced fade information available at the remote data-signal terminal in order to optimize the data transfer rate. Experiments were conducted to measure the irradiance in both the direct and the retro-reflected beams. Both on axis and off-axis components were recorded in order to further study the enhancement in the scintillation index observed in the retro-reflected beam. Measurements were made over a 1.8 km terrestrial range at AP Hill, Virginia. The degree of correlation of the received irradiance between the direct and double passage beams is found to approach 90% on-axis and 70% outside of the Fresnel zone radius. The scintillation index in the retro-reflected beam is enhanced on axis due to reciprocal optical paths. The measured scintillation indices, and the correlation of the retro-reflected beam with the direct beam, are compared with a point source, point scatterer, and point receiver model in the strong scintillation approximation. PMID- 26560629 TI - US Naval Research Laboratory focus issue: introduction. AB - Rather than concentrate on a single topic, this feature issue presents the wide variety of research in optics that takes place at a single institution, the United States Naval Research Laboratory (NRL) and is analogous to an NRL feature issue published in Applied Optics in 1967. NRL is the corporate research laboratory for the Navy and Marine Corps. It conducts a broadly based multidisciplinary program of scientific research and advanced technological development in the physical, engineering, space, and environmental sciences related to maritime, atmospheric, and space domains. NRL's research is directed toward new and improved materials, techniques, equipment, and systems in response to identified and anticipated Navy needs. A number of articles in this issue review progress in broader research areas while other articles present the latest results on specific topics. PMID- 26560632 TI - Preformed Seeds Modulate Native Insulin Aggregation Kinetics. AB - Insulin aggregates under storage conditions via disulfide interchange reaction. It is also known to form aggregates at the site of repeated injections in diabetes patients, leading to injection amyloidosis. This has fueled research in pharmaceutical and biotechnology industry as well as in academia to understand factors that modulate insulin stability and aggregation. The main aim of this study is to understand the factors that modulate aggregation propensity of insulin under conditions close to physiological and measure effect of "seeds" on aggregation kinetics. We explored the aggregation kinetics of insulin at pH 7.2 and 37 degrees C in the presence of disulfide-reducing agent dithiothreitol (DTT), using spectroscopy (UV-visible, fluorescence, and Fourier transform infrared spectroscopy) and microscopy (scanning electron microscopy, atomic force microscopy) techniques. We prepared insulin "seeds" by incubating disulfide reduced insulin at pH 7.2 and 37 degrees C for varying lengths of time (10 min to 12 h). These seeds were added to the native protein and nucleation-dependent aggregation kinetics was measured. Aggregation kinetics was fastest in the presence of 10 min seeds suggesting they were nascent. Interestingly, intermediate seeds (30 min to 4 h incubation) resulted in formation of transient fibrils in 4 h that converted to amorphous aggregates upon longer incubation of 24 h. Overall, the results show that insulin under disulfide reducing conditions at pH and temperature close to physiological favors amorphous aggregate formation and seed "maturity" plays an important role in nucleation dependent aggregation kinetics. PMID- 26560630 TI - The pig X and Y Chromosomes: structure, sequence, and evolution. AB - We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution. PMID- 26560631 TI - The chromatin environment shapes DNA replication origin organization and defines origin classes. AB - To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile. PMID- 26560633 TI - An alternative clean-up column for the determination of polychlorinated biphenyls in solid matrices. AB - The need for continuous monitoring of polychlorinated biphenyls (PCBs) has necessitated the development of analytical techniques that are sensitive and selective with minimal reagent requirement. In light of this, we developed a column for clean-up of soil and sediment extracts, which is less demanding in terms of the amount of solvent and sorbent. The dual-layer column consists of acidified silica gel and molecularly imprinted polymers (MIPs). MIPs were synthesized via aqueous suspension polymerization using PCB 15 as the dummy template, 4-vinylpyridine as the functional monomer and ethylene glycol dimethacrylate as the cross-linker and the obtained particles characterized via SEM, BET, and batch rebinding assays. Pre-concentration of the spiked real-world water sample using MISPE gave recoveries between 85.2 and 104.4% (RSD < 8.69). On the other hand, the specific dual-layer column designed for clean-up of extracts from complex matrices provided recoveries of 91.6-102.5% (RSD < 4%) for spiked soil, which was comparable to clean-up using acidified silica (70.4-90.5%; RSD < 3.72%) and sulfoxide modified silica (89.7-103.0%; RSD < 13.0%). However, the polymers were reusable maintaining recoveries of 79.8-111.8% after 30 cycles of regeneration and re-use, thereby availing a cost-effective clean-up procedure for continuous monitoring of PCBs. Method detection limits were 0.01-0.08 ng g(-1) and 0.002-0.01 ng mL(-1) for solid matrices and water, respectively. PMID- 26560634 TI - Heterogeneity in the three-year course of major depression among older adults. AB - OBJECTIVE: The objective of this research was to identify distinct trajectories of recovery in older depressed patients in order to identify optimal samples and points for interventions. METHODS: The sample was 368 patients ages 60 years and older diagnosed with major depression and enrolled in a naturalistic treatment study and followed for up to 3 years. RESULTS: A model with four trajectory classes fit the data best: a quick recovery class (43%), a persistent moderate symptom class (27%), a persistent high symptom class (15%), and a slow recovery class (15%). Compared with patients in the quick recovery class, patients in the persistent moderate symptom class had more instrumental activities of daily living/mobility limitations and lower levels of subjective social support. Patients in the persistent high symptom class had higher levels of perceived stress and lower levels of social support compared with those with a quick recovery. Patients in the slow recovery class had a younger age of onset compared with those in the quick recovery group. In multinomial logistic regression, levels of perceived stress and social support at baseline significantly differed across classes controlling for demographic and health variables. CONCLUSIONS: Older patients diagnosed with major depression can have varying patterns of response to treatment. Interventions targeting those patients with higher levels of perceived stress and lower levels of subjective social support at the time of the index episode may lead to more favorable long-term trajectories. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26560635 TI - Grape seed and skin extract protects against arsenic trioxide induced oxidative stress in rat heart. AB - Arsenic is a metalloid found in water, soil, and air from natural and anthropogenic sources, and is commonly found in inorganic as well as organic forms. The clinical use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) is limited by its cardiotoxic side effects. Grape seed and skin extract (GSSE) is a polyphenolic mixture with antioxidant properties. This study aimed to evaluate the protective effect of GSSE on arsenic induced cardiac oxidative stress and injury. Animals exposed to 2.5 mg/kg As2O3 for 21 days exhibited a relevant increase in heart lipoperoxidation, protein carbonylation, and inflammation, as well as a drop in the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, As2O3 disturbed heart lipidemia and lipase activity, transition metals distribution and the associated enzymes, intracellular mediators such as calcium and the associated calpain activity, as well as myocardial architecture. Treatment with 4 g/kg GSSE protected against most of the deleterious effects provoked by As2O3. Our data suggest that GSSE has the potential to protect against As2O3-induced cardiotoxicity. PMID- 26560637 TI - Relation entre la mastication et la qualite de l'alimentation des aines de l'Etude longitudinale quebecoise sur la nutrition et le vieillissement (NuAge). AB - The objective of this study was to assess the relationship between the quality of mastication and dietary intake among community-dwelling older adults (67-84 years). A secondary analysis of data collected upon entry of participants in the NuAge study was effected. Perceived masticatory efficiency (n=1793) was measured using a questionnaire inspired by the Oral Health Impact Profile. Direct assessment of masticatory efficiency was carried out in a subsample (n=94), using a validated clinical test (Swallowing Threshold Test Index, 0-100%). Dietary intake was calculated from three non-consecutive 24h recalls. Mean scores indicate good perceived masticatory efficiency (Men:26.22+/-0.19/28;Women:25.81+/ 0.21/28), but weak assessed efficiency (Men:60.8% [CI(57.3-64.2)]; Women:61.2% [CI(57.7-64.7)]). Multivariate regression analysis, adjusting for confounding variables (age, sex, schooling, living alone, income, smoking, chronic conditions, functional autonomy), showed that masticatory efficiency (measured or perceived) was not associated with intake of fruits/vegetables, protein, vitamin C or folic acid. PMID- 26560636 TI - Inhibition of myeloperoxidase at the peak of experimental autoimmune encephalomyelitis restores blood-brain barrier integrity and ameliorates disease severity. AB - Oxidative stress is thought to contribute to disease pathogenesis in the central nervous system (CNS) disease multiple sclerosis (MS). Myeloperoxidase (MPO), a potent peroxidase that generates toxic radicals and oxidants, is increased in the CNS during MS. However, the exact mechanism whereby MPO drives MS pathology is not known. We addressed this question by inhibiting MPO in mice with experimental autoimmune encephalomyelitis (EAE) using our non-toxic MPO inhibitor N-acetyl lysyltyrosylcysteine amide (KYC). We found that therapeutic administration of KYC for 5 days starting at the peak of disease significantly attenuated EAE disease severity, reduced myeloid cell numbers and permeability of the blood-brain barrier. These data indicate that inhibition of MPO by KYC restores blood-brain barrier integrity thereby limiting migration of myeloid cells into the CNS that drive EAE pathogenesis. In addition, these observations indicate that KYC may be an effective therapeutic agent for the treatment of MS. We propose that during experimental autoimmune encephalomyelitis (EAE) onset macrophages and neutrophils migrate into the CNS and upon activation release myeloperoxidase (MPO) that promotes disruption of the blood-brain barrier (BBB) and disease progression. KYC restores BBB function by inhibiting MPO activity and in so doing ameliorates disease progression. PMID- 26560638 TI - Novel carboxymethyl cellulose based nanocomposite membrane: Synthesis, characterization and application in water treatment. AB - Significant efforts have been made to develop composite membranes with high adsorption efficiencies for water treatment. In this study, a carboxymethyl cellulose-graft-poly(acrylic acid) membrane was synthesized in the presence of silica gel, which was used as an inorganic support. Then, different amounts of bentonite were introduced to the carboxymethyl cellulose (CMC) grafted networks as a multifunctional crosslinker, and nanocomposite membranes were prepared. The nanocomposite membranes were characterized using Fourier transform infrared spectroscopy, and scanning electron microscopy, which revealed their compositions and surface morphologies. The novel synthesized nanocomposite membranes were utilized as adsorbents for the removal of crystal violet (CV) and cadmium (Cd (II)) ions, which were selected as representatives of a dye and a heavy metal, respectively. We explored the effects of various parameters, such as time, pH, temperature, initial concentration of adsorbate solution and amount of adsorbent, on membrane adsorption capacity. Furthermore, the kinetic, adsorption isotherm models and thermodynamic were employed for the description of adsorption processes. The maximum adsorption capacities of membranes for CV and Cd (II) ions were found to be 546 and 781 mg g(-1), respectively. The adsorption of adsorbate ions by all types of nanocomposite membranes followed pseudo-second-order kinetic model and was best fit with the Freundlich adsorption isotherm. The results indicated that the synthesized nanocomposite membrane is an efficient adsorbent for the removal of cationic dye and metal contaminants from aqueous solution during water treatment. PMID- 26560639 TI - Chlorination and oxidation of sulfonamides by free chlorine: Identification and behaviour of reaction products by UPLC-MS/MS. AB - Sulfonamides (SAs) are one class of the most widely used antibiotics around the world and have been frequently detected in municipal wastewater and surface water in recent years. Their transformation in waste water treatment plants (WWTP) and in water treatment plants (WTP), as well as, their fate and transport in the aquatic environment are of concern. The reaction of six sulfonamides (sulfamethoxazole, sulfapyridine, sulfamethazine, sulfamerazine, sulfathiazole and sulfadiazine) with free chlorine was investigated at a laboratory scale in order to identify the main chlorination by-products. A previously validated method, liquid chromatography/mass spectrometry, was used to analyse SAs and their chlorination by-products. At room temperature, pH 6-7, reaction times of up to 2 h and an initial concentration of 2 mg/L of free chlorine, the majority of SAs suffered degradation of around 65%, with the exception of sulfamethoxazole and sulfathiazole (20%). The main reaction of SAs with free chlorine occurred in the first minute. PMID- 26560640 TI - Remediation and phytotoxicity of decabromodiphenyl ether contaminated soil by zero valent iron nanoparticles immobilized in mesoporous silica microspheres. AB - Polybrominated diphenyl ethers (PBDEs) are a new class of environmental pollutants which easily accumulated in the soil, especially at e-waste sites. However, knowledge about their phytotoxicity after degradation is not well understood. Nano zero valent iron (nZVI) immobilized in mesoporous silica microspheres covered with FeOOH (SiO2@FeOOH@Fe) synthesized in this study was utilized to remove decabromodiphenyl ether (BDE209) from soil. Results revealed that the removal efficiency of BDE209 can be achieved 78% within 120 h using a dosage of 0.165 g g(-1) and a pH of 5.42. Furthermore, the removal efficiency enhanced with increasing soil moisture content and the decreasing of initial BDE209 concentration. Phytotoxicity assays (biomass and germination rate, shoots and roots elongation of Chinese cabbage) were carried out to provide a preliminary risk assessment of treated soil for the application of SiO2@FeOOH@Fe. PMID- 26560641 TI - So close, so different: geothermal flux shapes divergent soil microbial communities at neighbouring sites. AB - This study is focused on the (micro)biogeochemical features of two close geothermal sites (FAV1 and FAV2), both selected at the main exhalative area of Pantelleria Island, Italy. A previous biogeochemical survey revealed high CH4 consumption and the presence of a diverse community of methanotrophs at FAV2 site, whereas the close site FAV1 was apparently devoid of methanotrophs and recorded no CH4 consumption. Next-Generation Sequencing (NGS) techniques were applied to describe the bacterial and archaeal communities which have been linked to the physicochemical conditions and the geothermal sources of energy available at the two sites. Both sites are dominated by Bacteria and host a negligible component of ammonia-oxidizing Archaea (phylum Thaumarchaeota). The FAV2 bacterial community is characterized by an extraordinary diversity of methanotrophs, with 40% of the sequences assigned to Methylocaldum, Methylobacter (Gammaproteobacteria) and Bejerickia (Alphaproteobacteria); conversely, a community of thermo-acidophilic chemolithotrophs (Acidithiobacillus, Nitrosococcus) or putative chemolithotrophs (Ktedonobacter) dominates the FAV1 community, in the absence of methanotrophs. Since physical andchemical factors of FAV1, such as temperature and pH, cannot be considered limiting for methanotrophy, it is hypothesized that the main limiting factor for methanotrophs could be high NH4(+) concentration. At the same time, abundant availability of NH4(+) and other high energy electron donors and acceptors determined by the hydrothermal flux in this site create more energetically favourable conditions for chemolithotrophs that outcompete methanotrophs in non-nitrogen-limited soils. PMID- 26560642 TI - Contact allergy to chlorhexidine in a tertiary dermatology clinic in Denmark. AB - BACKGROUND: Chlorhexidine is a widely used disinfectant in the healthcare setting and in cosmetic products. A high prevalence of chlorhexidine contact allergy was reported in Denmark in the 1980s (2.0-5.4% of patients patch tested). It is unknown whether the prevalence is still high, which products cause the contact allergy, and whether accidental re-exposure occurs in some patients. OBJECTIVES: To estimate the prevalence of chlorhexidine contact allergy in a tertiary dermatology clinic in Denmark; to investigate whether patch testing with both chlorhexidine diacetate and chlorhexidine digluconate is necessary; to investigate how many patients have combined immediate-type allergy and contact allergy; and to identify which products cause chlorhexidine contact allergy, and whether patients are accidentally re-exposed. METHODS: This was a retrospective study including all patients patch tested with chlorhexidine during 2003-2013 at the Department of Dermato-Allergology at Copenhagen University Hospital Gentofte (n = 8497). All patients with a positive patch test reaction to chlorhexidine were sent a questionnaire comprising questions about the cause of the allergy and re-exposure. RESULTS: Overall, 1.0% (n = 82) of all patients patch tested with chlorhexidine were positive. A decrease in the prevalence was observed over time, most likely because of lowering of the test concentration from 1.0 to 0.5% in 2008. Of the 82 patients, 28 (0.3%) had positive test reactions to both chlorhexidine salts, 43 (0.5%) had a positive test reaction only to chlorhexidine diacetate, and 11 (0.1%) had a positive test reaction to chlorhexidine digluconate. Three patients were both patch test-positive and prick test positive. A known cause of the allergy was reported by 19 patients (40%) in the questionnaire: the products used in the healthcare setting were mainly reported, but some reported cosmetic products. Accidental re-exposure was reported by 15 patients (32%), of whom 13 reported symptoms. CONCLUSIONS: The prevalence of chlorhexidine contact allergy does not seem to be higher in Denmark than in other European countries. Patch testing with both chlorhexidine diacetate and chlorhexidine digluconate may be beneficial. Testing for immediate-type allergy in patients with a positive patch test reaction to chlorhexidine is recommended. Chlorhexidine-containing products used in the healthcare setting and in cosmetics are potential causes of sensitization and allergy. Re-exposure is common, highlighting the fact that patients and healthcare personnel need to be well informed about possible sources of exposure. PMID- 26560644 TI - Quantitative Neutron Dark-field Imaging through Spin-Echo Interferometry. AB - Neutron dark-field imaging constitutes a seminal progress in the field of neutron imaging as it combines real space resolution capability with information provided by one of the most significant neutron scattering techniques, namely small angle scattering. The success of structural characterizations bridging the gap between macroscopic and microscopic features has been enabled by the introduction of grating interferometers so far. The induced interference pattern, a spatial beam modulation, allows for mapping of small-angle scattering signals and hence addressing microstructures beyond direct spatial resolution of the imaging system with high efficiency. However, to date the quantification in the small angle scattering regime is severely limited by the monochromatic approach. To overcome such drawback we here introduce an alternative and more flexible method of interferometric beam modulation utilizing a spin-echo technique. This novel method facilitates straightforward quantitative dark-field neutron imaging, i.e. the required quantitative microstructural characterization combined with real space image resolution. For the first time quantitative microstructural reciprocal space information from small angle neutron scattering becomes available together with macroscopic image information creating the potential to quantify several orders of magnitude in structure sizes simultaneously. PMID- 26560643 TI - Medically treated exacerbations in COPD by GOLD 1-4: A valid, robust, and seemingly low-biased definition. AB - AIM: We hypothesized that medically treated exacerbations in COPD defined as treatments with oral corticosteroids alone or in combination with antibiotics by register linkage with a nationwide prescription registry is a valid, robust and low-biased measure of exacerbations. METHODS: A total of 13,591 individuals with COPD in the Copenhagen General Population Study (2003-2013) were linked to the Danish prescription registry. Exacerbations were defined as dispensing of oral corticosteroids alone or in combination with antibiotics, dispensed less than four weeks apart during three years of follow-up. Construct validity of this definition of medically treated exacerbations was assessed by studying baseline determinants as well as by studying the association between GOLD 1 through 4 grades and time to first exacerbation during follow-up. RESULTS: Among individuals with COPD, 964 individuals (7.1%) had at least one exacerbation during follow-up. At baseline, comparing those with versus without exacerbations during follow-up, FEV1, 72% of predicted vs. 85% (p < 0.001), previous exacerbations, 43% vs. 11% (p < 0.001), breathlessness, 33% vs. 14% (p < 0.001), and use of inhaled medications, 54% vs. 14% (p < 0.001) were associated with exacerbations. Compared to individuals with GOLD 1, the multivariable hazard ratio (HR) for exacerbations was HR = 17.4 (12.3-24.5, p < 0.001) for GOLD 4, HR = 4.8 (3.9-5.9, p < 0.001) for GOLD 3, and HR = 2.0 (1.7-2.3, p < 0.001) for GOLD 2. In sensitivity analyses, our definition of exacerbations was robust and without major biases. CONCLUSIONS: Compared to individuals with GOLD 1, the risk of exacerbations was 17-fold for GOLD 4, 5-fold for GOLD 3, and 2-fold for GOLD 2. Medically treated exacerbations defined by register linkage seem a valid, robust, and low-biased measure of exacerbations in COPD. PMID- 26560645 TI - Life without Fe-S clusters. AB - Fe-S clusters are critically important cofactors implicated in numerous cellular processes, including respiration, amino acid biosynthesis, cofactor biosynthesis, tRNA modification, DNA repair and regulation of gene expression. In the accompanying manuscript, Tanaka et al. show that reengineering of the isoprenoid biosynthetic pathway in E. coli (to bypass the usage of essential Fe-S cluster proteins by inserting the mevalonate pathway) can offset the indispensability of the Fe-S cluster biosynthetic systems. They show that the resulting Deltaisc Deltasuf double mutants supplemented with mevalonate can grow slowly without detectable Fe-S cluster proteins. This result is astounding and raises interesting questions about what is essential and what is dispensable in the compendium of Fe-S cluster protein functions in this cell. PMID- 26560673 TI - Tissue Distribution and Whole Body Burden of the Chlorinated Polyfluoroalkyl Ether Sulfonic Acid F-53B in Crucian Carp (Carassius carassius): Evidence for a Highly Bioaccumulative Contaminant of Emerging Concern. AB - Following the global actions to phase out perfluoroctanesulfonic acid (PFOS) a large number of alternative per- and polyfluoroalkyl substances, with poorly defined hazard properties, are being used in increasing quantities. Here, we report on the first detection of the chlorinated polyfluoroalkyl ether sulfonic acid F-53B in biological samples and determine the tissue distribution and whole body bioaccumulation factors (BAFwhole body) in crucian carp (Carassius carassius). Analysis of fish samples from Xiaoqing River (XR) and Tangxun Lake (TL) demonstrated a similar level of F-53B contamination with median concentrations in blood of 41.9 and 20.9 ng/g, respectively. Tissue/blood ratios showed that distribution of F-53B primarily occurs to the kidney (TL: 0.48, XR: 0.54), gonad (TL: 0.36, XR: 0.54), liver (TL: 0.38, XR: 0.53), and heart (TL: 0.47, XR: 0.47). Median Log BAFwhole body values for F-53B (XR: 4.124, TL: 4.322) exceeded regulatory bioaccumulation criterion and were significantly higher than those of PFOS in the same data sets (XR: 3.430, TL: 3.279). On the basis of its apparent omnipresence and strong bioaccumulation propensity, it is hypothesized that F-53B could explain a significant fraction of previously unidentified organofluorine in biological samples from China, and regulatory actions for this compound are encouraged. PMID- 26560674 TI - Toddlers' bias to look at average versus obese figures relates to maternal anti fat prejudice. AB - Anti-fat prejudice (weight bias, obesity stigma) is strong, prevalent, and increasing in adults and is associated with negative outcomes for those with obesity. However, it is unknown how early in life this prejudice forms and the reasons for its development. We examined whether infants and toddlers might display an anti-fat bias and, if so, whether it was influenced by maternal anti fat attitudes through a process of social learning. Mother-child dyads (N=70) split into four age groups participated in a preferential looking paradigm whereby children were presented with 10 pairs of average and obese human figures in random order, and their viewing times (preferential looking) for the figures were measured. Mothers' anti-fat prejudice and education were measured along with mothers' and fathers' body mass index (BMI) and children's television viewing time. We found that older infants (M=11months) had a bias for looking at the obese figures, whereas older toddlers (M=32months) instead preferred looking at the average-sized figures. Furthermore, older toddlers' preferential looking was correlated significantly with maternal anti-fat attitudes. Parental BMI, education, and children's television viewing time were unrelated to preferential looking. Looking times might signal a precursor to explicit fat prejudice socialized via maternal anti-fat attitudes. PMID- 26560676 TI - Video tracking analysis of behavioral patterns during estrus in goats. AB - Here, we report a new method for measuring behavioral patterns during estrus in goats based on video tracking analysis. Data were collected from cycling goats, which were in estrus (n = 8) or not in estrus (n = 8). An observation pen (2.5 m * 2.5 m) was set up in the corner of the female paddock with one side adjacent to a male paddock. The positions and movements of goats were tracked every 0.5 sec for 10 min by using a video tracking software, and the trajectory data were used for the analysis. There were no significant differences in the durations of standing and walking or the total length of movement. However, the number of approaches to a male and the duration of staying near the male were higher in goats in estrus than in goats not in estrus. The proposed evaluation method may be suitable for detailed monitoring of behavioral changes during estrus in goats. PMID- 26560675 TI - Developmental dissociation between the maturation of procedural memory and declarative memory. AB - Declarative memory and procedural memory are known to be two fundamentally different kinds of memory that are dissociable in their psychological characteristics and measurement (explicit vs. implicit) and in the neural systems that subserve each kind of memory. Declarative memory abilities are known to improve from childhood through young adulthood, but the developmental maturation of procedural memory is largely unknown. We compared 10-year-old children and young adults on measures of declarative memory and working memory capacity and on four measures of procedural memory that have been strongly dissociated from declarative memory (mirror tracing, rotary pursuit, probabilistic classification, and artificial grammar). Children had lesser declarative memory ability and lesser working memory capacity than adults, but children exhibited learning equivalent to adults on all four measures of procedural memory. Therefore, declarative memory and procedural memory are developmentally dissociable, with procedural memory being adult-like by age 10years and declarative memory continuing to mature into young adulthood. PMID- 26560677 TI - Computer-aided detection of cerebral microbleeds in susceptibility-weighted imaging. AB - Susceptibility-weighted imaging (SWI) is recognized as the preferred MRI technique for visualizing cerebral vasculature and related pathologies such as cerebral microbleeds (CMBs). Manual identification of CMBs is time-consuming, has limited reliability and reproducibility, and is prone to misinterpretation. In this paper, a novel computer-aided microbleed detection technique based on machine learning is presented: First, spherical-like objects (potential CMB candidates) with their corresponding bounding boxes were detected using a novel multi-scale Laplacian of Gaussian technique. A set of robust 3-dimensional Radon- and Hessian-based shape descriptors within each bounding box were then extracted to train a cascade of binary random forests (RF). The cascade consists of consecutive independent RF classifiers with low to high posterior probability constraints to handle imbalanced training sets (CMBs and non-CMBs), and to progressively improve detection rates. The proposed method was validated on 66 subjects whose CMBs were manually stratified into "possible" and "definite" by two medical experts. The proposed technique achieved a sensitivity of 87% and an average false detection rate of 27.1 CMBs per subject on the "possible and definite" set. A sensitivity of 93% and false detection rate of 10 CMBs per subject was also achieved on the "definite" set. The proposed automated approach outperforms state of the art methods, and promises to enhance manual expert screening. Benefits include improved reliability, minimization of intra-rater variability and a reduction in assessment time. PMID- 26560678 TI - Women in Cardiology: Very Few, Different Work, Different Pay. PMID- 26560679 TI - Work Activities and Compensation of Male and Female Cardiologists. AB - BACKGROUND: Much remains unknown about experiences, including working activities and pay, of women in cardiology, which is a predominantly male specialty. OBJECTIVES: The goal of this study was to describe the working activities and pay of female cardiologists compared with their male colleagues and to determine whether sex differences in compensation exist after accounting for differences in work activities and other characteristics. METHODS: The personal, job, and practice characteristics of a national sample of practicing cardiologists were described according to sex. We applied the Peters-Belson technique and multivariate regression analysis to evaluate whether gender differences in compensation existed after accounting for differences in other measured characteristics. The study used 2013 data reported by practice administrators to MedAxiom, a subscription-based service provider to cardiology practices. Data regarding cardiologists from 161 U.S. practices were included, and the study sample included 2,679 subjects (229 women and 2,450 men). RESULTS: Women were more likely to be specialized in general/noninvasive cardiology (53.1% vs. 28.2%), and a lower proportion (11.4% vs. 39.3%) reported an interventional subspecialty compared with men. Job characteristics that differed according to sex included the proportion working full-time (79.9% vs. 90.9%; p < 0.001), the mean number of half-days worked (387 vs. 406 days; p = 0.001), and mean work relative value units generated (7,404 vs. 9,497; p < 0.001) for women and men, respectively. Peters-Belson analysis revealed that based on measured job and productivity characteristics, the women in this sample would have been expected to have a mean salary that was $31,749 (95% confidence interval: $16,303 to $48,028) higher than that actually observed. Multivariate analysis confirmed the direction and magnitude of the independent association between sex and salary. CONCLUSIONS: Men and women practicing cardiology in this national sample had different job activities and salaries. Substantial sex-based salary differences existed even after adjusting for measures of personal, job, and practice characteristics. PMID- 26560680 TI - Towards cell-free isobutanol production: Development of a novel immobilized enzyme system. AB - Producing fuels and chemical intermediates with cell cultures is severely limited by low product concentrations (<=0.2%(v/v)) due to feedback inhibition, cell instability, and lack of economical product recovery processes. We have developed an alternate simplified production scheme based on a cell-free immobilized enzyme system. Two immobilized enzymes (keto-acid decarboxylase (KdcA) and alcohol dehydrogenase (ADH)) and one enzyme in solution (formate dehydrogenase (FDH) for NADH recycle) produced isobutanol titers 8 to 20 times higher than the highest reported titers with S. cerevisiae on a mol/mol basis. These high conversion rates and low protein leaching were achieved by covalent immobilization of enzymes (ADH) and enzyme fusions (fKdcA) on methacrylate resin. The new enzyme system without in situ removal of isobutanol achieved a 55% conversion of ketoisovaleric acid to isobutanol at a concentration of 0.135 (mole isobutanol produced for each mole ketoisovaleric acid consumed). Further increasing titer will require continuous removal of the isobutanol using an in situ recovery system. PMID- 26560681 TI - Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii. AB - Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment. PMID- 26560682 TI - Gas Chromatography Coupled to Atmospheric Pressure Chemical Ionization FT-ICR Mass Spectrometry for Improvement of Data Reliability. AB - Atmospheric pressure chemical ionization (APCI) offers the advantage of molecular ion information with low fragmentation. Hyphenating APCI to gas chromatography (GC) and ultrahigh resolution mass spectrometry (FT-ICR MS) enables an improved characterization of complex mixtures. Data amounts acquired by this system are very huge, and existing peak picking algorithms are usually extremely time consuming, if both gas chromatographic and ultrahigh resolution mass spectrometric data are concerned. Therefore, automatic routines are developed that are capable of handling these data sets and further allow the identification and removal of known ionization artifacts (e.g., water- and oxygen-adducts, demethylation, dehydrogenation, and decarboxylation). Furthermore, the data quality is enhanced by the prediction of an estimated retention index, which is calculated simply from exact mass data combined with a double bond equivalent correction. This retention index is used to identify mismatched elemental compositions. The approach was successfully tested for analysis of semivolatile components in heavy fuel oil and diesel fuel as well as primary combustion particles emitted by a ship diesel research engine. As a result, 10-28% of the detected compounds, mainly low abundant species, classically assigned by using only the mass spectrometric information, were identified as not valid and removed. Although GC separation is limited by the slow acquisition rate of the FT ICR MS (<1 Hz), a database driven retention time comparison, as commonly used for low resolution GC/MS, can be applied for revealing isomeric information. PMID- 26560683 TI - Targeted therapy for stress urinary incontinence: a systematic review based on clinical trials. AB - INTRODUCTION: Controversy exists regarding the therapeutic benefit of cell-based therapy in the treatment of stress urinary incontinence (SUI). AREAS COVERED: The aim of this systematic review was to evaluate evidence regarding the therapeutic effect and safety of cell-based therapy in the treatment of SUI and to propose a new approach to SUI treatment utilizing tissue engineering methodologies. We have thoroughly reviewed the literature using PubMed in order to identify only original, clinical studies involving cell therapy for SUI. EXPERT OPINION: Cell based therapy, as practiced today, is a safe but ineffective method for SUI treatment. The key to an optimal therapeutic outcome in SUI is accurate diagnosis combined with targeted therapy. Targeted therapy in SUI should be based on cell implantation to restore and regenerate the damaged urethral sphincter and/or the construction of a neo-pubourethral ligament utilizing tissue engineering methodologies. PMID- 26560684 TI - Accessibility of outpatient healthcare providers for wheelchair users: Pilot study. AB - The Americans with Disabilities Act (ADA) requires full and equal access to healthcare services and facilities, yet studies indicate individuals with mobility disabilities receive less than thorough care as a result of ADA noncompliance. The objective of our pilot study was to assess ADA compliance within a convenience sample of healthcare clinics affiliated with a statewide healthcare network. Site assessments based on the ADA Accessibility Guidelines for Buildings and Facilities were performed at 30 primary care and specialty care clinics. Clinical managers completed a questionnaire on standard practices for examining and treating patients whose primary means of mobility is a wheelchair. We found a majority of restrooms (83%) and examination rooms (93%) were noncompliant with one or more ADA requirements. Seventy percent of clinical managers reported not owning a height-adjustable examination table or wheelchair accessible weight scale. Furthermore, patients were examined in their wheelchairs (70%-87%), asked to bring someone to assist with transfers (30%), or referred elsewhere due to an inaccessible clinic (6%). These methods of accommodation are not compliant with the ADA. We recommend clinics conduct ADA self-assessments and provide training for clinical staff on the ADA and requirements for accommodating individuals with mobility disabilities. PMID- 26560685 TI - Infectious Complications Following Small Bowel Transplantation. AB - Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all patients undergoing SBT from 2004 to 2013 in Spain. Sixty-nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow-up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant-days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio [HR]: 2.21; 95% confidence interval [CI]: 1.02 4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40-12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35-115.91; p < 0.001). In conclusion, infection is the most frequent complication and the leading cause of death following SBT. Posttransplant RRT and retransplantation identify those recipients at high risk for developing OI and IFD. PMID- 26560687 TI - Hydrogen Peroxide Complex of Zinc. AB - Metal(H2O2) complexes have been implicated in kinetic and computational studies but have never been observed. Accordingly, H2O2 has been described as a very weak ligand. We report the first metal(H2O2) adduct, which is made possible by incorporating intramolecular hydrogen-bonding interactions with bound H2O2. This Zn(II)(H2O2) complex decays in solution by a second-order process that is slow enough to enable characterization of this species by X-ray crystallography. This report speaks to the intermediacy of metal(H2O2) adducts in chemistry and biology and opens the door to exploration of these species in oxidation catalysis. PMID- 26560686 TI - Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals. AB - Although transfer of electrophilic alkoxyl ("RO+") from organic peroxides to organometallics offers a complement to traditional methods for etherification, application has been limited by constraints associated with peroxide reactivity and stability. We now demonstrate that readily prepared tetrahydropyranyl monoperoxyacetals react with sp(3) and sp(2) organolithium and organomagnesium reagents to furnish moderate to high yields of ethers. The method is successfully applied to the synthesis of alkyl, alkenyl, aryl, heteroaryl, and cyclopropyl ethers, mixed O,O-acetals, and S,S,O-orthoesters. In contrast to reactions of dialkyl and alkyl/silyl peroxides, the displacements of monoperoxyacetals provide no evidence for alkoxy radical intermediates. At the same time, the high yields observed for transfer of primary, secondary, or tertiary alkoxides, the latter involving attack on neopentyl oxygen, are inconsistent with an SN2 mechanism. Theoretical studies suggest a mechanism involving Lewis acid promoted insertion of organometallics into the O-O bond. PMID- 26560688 TI - A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH dependent Ca2+ release from acidic Ca2+ stores. AB - Ambroxol (Ax) is a frequently prescribed drug used to facilitate mucociliary clearance, but its mode of action is yet poorly understood. Here we show by X-ray spectroscopy that Ax accumulates in lamellar bodies (LBs), the surfactant storing, secretory lysosomes of type II pneumocytes. Using lyso- and acidotropic substances in combination with fluorescence imaging we confirm that these vesicles belong to the class of acidic Ca(2+) stores. Ax lead to a significant neutralization of LB pH, followed by intracellular Ca(2+) release, and to a dose dependent surfactant exocytosis. Ax-induced Ca(2+) release was significantly reduced and slowed down by pretreatment of the cells with bafilomycin A1 (Baf A1), an inhibitor of the vesicular H(+) ATPase. These results could be nearly reproduced with NH3/NH4(+). The findings suggest that Ax accumulates within LBs and severely affects their H(+) and Ca(2+) homeostasis. This is further supported by an Ax-induced change of nanostructural assembly of surfactant layers. We conclude that Ax profoundly affects LBs presumably by disordering lipid bilayers and by acting as a weak base. The pH change triggers - at least in part - Ca(2+) release from stores and secretion of surfactant from type II cells. This novel mechanism of Ax as a lysosomal secretagogue may also play a role for its recently discussed use for lysosomal storage and other degenerative diseases. PMID- 26560689 TI - Current concepts and future potential in neoadjuvant chemotherapy for esophageal cancer. AB - Many trials have evaluated preoperative chemotherapy for the treatment of locally advanced esophageal cancer (LAEC). Most studies were small with conflicting results and no clear evidence of survival advantage. However, two large trials that included squamous cell carcinomas and adenocarcinomas of the esophagus produced opposite outcomes with one showing limited benefit and the other showing none. Recent meta-analyses suggest only a modest benefit from induction chemotherapy in the treatment of LAEC. Two factors associated with prolonged survival are: (1) an R0 resection and (2) pathological complete remission. Preoperative chemotherapy is preferred in Europe for adenocarcinomas; however, chemoradiation has been the treatment of choice in the US. The individualization and optimization of therapy for esophageal cancer patients may come from an in depth understanding of molecular biology and the development of predictive biomarkers. The use of targeted and immunotherapy agents in the preoperative setting are also promising and warrant further evaluation. PMID- 26560690 TI - University-level nutrition training in West Africa: cost and financing issues. AB - BACKGROUND: There is a serious shortage of skilled nutrition professionals in West Africa. Investing in nutrition training is one of the strategies for strengthening the human resource base in nutrition. However, little is known about how nutrition training in the region is financed and the levels of tuition fees charged. The purpose of this study was to provide a comprehensive assessment about the levels of tuition fees charged for nutrition training in the West Africa region and to determine to what extent this is of reach to the average student. METHODOLOGY: The data for this study were obtained from 74 nutrition degree programs operating in nine West African countries in 2013 through semi structured interviews during on-site visits or through self-administered questionnaires. They included the age of the programs, school ownership, tuition fees, financial assistance, and main sources of funding. Tuition fees (in 2013 US$) were expressed per program to enable uniformity and comparability. Simple descriptive and bivariate analyses were performed. RESULTS: Results from 74 nutrition training programs in nine countries showed a wide variation in tuition fees within and between countries. The tuition fees for bachelor's, master's, and doctoral programs, respectively, ranged from 372 to 4,325 (mean: 2,353); 162 to 7,678 (mean: 2,232); and 369 to 5,600 (mean: 2,208). The tuition fees were significantly higher (p<0.05) in private institutions than in public institutions (mean: US$3,079 vs. US$2,029 for bachelor's programs; US$5,118 vs. US$1,820 for master's programs; and US$3,076 vs. US$1,815 for doctoral programs). The difference in the tuition fees between Francophone and Anglophone countries was not statistically significant (mean: US$2,570 vs. US$2,216 for bachelor's programs; US$2,417 vs. US$2,147 for master's programs; US$3,285 vs. US$2,055 for doctoral programs). In most countries, the tuition fees appeared to be out of reach of the average student. Recent master's programs appeared to charge higher fees than older ones. We found a significant negative correlation between tuition fees and the age of the program, after controlling for school ownership (r=-0.33, p<0.001). CONCLUSIONS: Our findings underscore the urgent need for national governments in the region to establish benchmarks and regulate nutrition training costs. In a region where the average annual gross national income (GNI) per capita is barely 890$, the rising cost of tuition fees is likely to hinder access of students from poor background to nutrition training. Governments should institute financing mechanisms such as scholarships, public-private partnerships, credit facilities, and donor funding to facilitate access to tertiary-level nutrition training in the region. PMID- 26560691 TI - The absence of physiological neonatal weight loss on the 1st-5th day is associated with decreased later physical indices. AB - AIM: To investigate associations between physiological neonatal weight loss on the 1st-5th day and physical indices from birth up to the age of 17 years. METHODS: Data were derived from the personal health records of healthy, full-term and breastfed children born in Vilnius in 1990 and 1996. Five hundred and thirty children (289 boys and 241 girls) who left a maternity unit on the 1st-5th day after birth were included in the analysis. RESULTS: Infants left the maternity unit on day 4.62 +/- 2.33. On the day of leaving a maternity unit, infants lost 105.06 +/- 130.48 g (2.85 +/- 3.65%) of birth weight. Girls who did not lose or gained weight after birth had already weighed less at birth (3163 +/- 547 and 3490 +/- 403 g, respectively, p < 0.01) and remained lighter up to the age of 17 years (54.3 +/- 8.7 and 60.8 +/- 10.1 kg at the age of 17 years respectively, p < 0.001). Girls who did not lose or gained weight after birth were also shorter than those who lost weight (164.3 +/- 5.7 and 168.6 +/- 5.4 cm at the age of 17 years, respectively, p < 0.001). CONCLUSION: Girls who did not lose or gained weight immediately after birth tended to remain shorter and lighter during childhood and adolescence. Only a few statistically significant differences were obtained in boys. PMID- 26560692 TI - NurA Is Endowed with Endo- and Exonuclease Activities that Are Modulated by HerA: New Insight into Their Role in DNA-End Processing. AB - The nuclease NurA and the ATPase HerA are present in all known thermophilic archaea and cooperate with the highly conserved MRE11/RAD50 proteins to facilitate efficient DNA double-strand break end processing during homologous recombinational repair. However, contradictory results have been reported on the exact activities and mutual dependence of these two enzymes. To understand the functional relationship between these two enzymes we deeply characterized Sulfolobus solfataricus NurA and HerA proteins. We found that NurA is endowed with exo- and endonuclease activities on various DNA substrates, including linear (single-stranded and double stranded) as well as circular molecules (single stranded and supercoiled double-stranded). All these activities are not strictly dependent on the presence of HerA, require divalent ions (preferably Mn2+), and are inhibited by the presence of ATP. The endo- and exonculease activities have distinct requirements: whereas the exonuclease activity on linear DNA fragments is stimulated by HerA and depends on the catalytic D58 residue, the endonuclease activity on circular double-stranded DNA is HerA-independent and is not affected by the D58A mutation. On the basis of our results we propose a mechanism of action of NurA/HerA complex during DNA end processing. PMID- 26560694 TI - Harm to Others from Substance Use and Abuse: The Underused Potential in Nationwide Registers. AB - This article considers the potential in using nationwide registers to study harm to others from substance use and abuse. The advantages of using registry data include the opportunity to include the data on the entire population nationwide and continuously updated longitudinal datasets; they allow for studying small subpopulations and have little missing data. Personal identification numbers and family numbers enable linkage of data from different registers. Such datasets can include extensive information on individual and family levels. In this article, we provide an introduction to nationwide registers and explain how they can be applied to investigate two types of third-party harms: harm to children and harm to partners/spouses from substance use and abuse in parents and partners/spouses. Finally, we discuss challenges, benefits, and ethical considerations regarding the use of such data. PMID- 26560693 TI - The molecular architecture of the Dam1 kinetochore complex is defined by cross linking based structural modelling. AB - Accurate segregation of chromosomes during cell division is essential. The Dam1 complex binds kinetochores to microtubules and its oligomerization is required to form strong attachments. It is a key target of Aurora B kinase, which destabilizes erroneous attachments allowing subsequent correction. Understanding the roles and regulation of the Dam1 complex requires structural information. Here we apply cross-linking/mass spectrometry and structural modelling to determine the molecular architecture of the Dam1 complex. We find microtubule attachment is accompanied by substantial conformational changes, with direct binding mediated by the carboxy termini of Dam1p and Duo1p. Aurora B phosphorylation of Dam1p C terminus weakens direct interaction with the microtubule. Furthermore, the Dam1p amino terminus forms an interaction interface between Dam1 complexes, which is also disrupted by phosphorylation. Our results demonstrate that Aurora B inhibits both direct interaction with the microtubule and oligomerization of the Dam1 complex to drive error correction during mitosis. PMID- 26560696 TI - Microstructures of Organometal Trihalide Perovskites for Solar Cells: Their Evolution from Solutions and Characterization. AB - The use of organometal trihalide perovskites (OTPs) in perovskite solar cells (PSCs) is revolutionizing the field of photovoltaics, which is being led by advances in solution processing of OTP thin films. First, we look at fundamental phenomena pertaining to nucleation/growth, coarsening, and microstructural evolution involved in the solution-processing of OTP thin films for PSCs from a materials-science perspective. Established scientific principles that govern some of these phenomena are invoked in the context of specific literature examples of solution-processed OTP thin films. Second, the nature and the unique characteristics of OTP thin-film microstructures themselves are discussed from a materials-science perspective. Finally, we discuss the challenges and opportunities in the characterization of OTP thin films for not only gaining a deep understanding of defects and microstructures but also elucidating classical and nonclassical phenomena pertaining to nucleation/growth, coarsening, and microstructural evolution in these films. The overall goal is to have deterministic control over the solution-processing of tailored OTP thin films with desired morphologies and microstructures. PMID- 26560697 TI - Recent research in flaxseed (oil seed) on molecular structure and metabolic characteristics of protein, heat processing-induced effect and nutrition with advanced synchrotron-based molecular techniques. AB - Advanced synchrotron radiation-based infrared microspectroscopy is able to reveal feed and food structure feature at cellular and molecular levels and simultaneously provides composition, structure, environment, and chemistry within intact tissue. However, to date, this advanced synchrotron-based technique is still seldom known to food and feed scientists. This article aims to provide detailed background for flaxseed (oil seed) protein research and then review recent progress and development in flaxseed research in ruminant nutrition in the areas of (1) dietary inclusion of flaxseed in rations; (2) heat processing effect; (3) assessing dietary protein; (4) synchrotron-based Fourier transform infrared microspectroscopy as a tool of nutritive evaluation within cellular and subcellular dimensions; (5) recent synchrotron applications in flaxseed research on a molecular basis. The information described in this paper gives better insight in flaxseed research progress and update. PMID- 26560699 TI - Opening clinical trial data: are the voluntary data-sharing portals enough? AB - Data generated by the numerous clinical trials conducted annually worldwide have the potential to be extremely beneficial to the scientific and patient communities. This potential is well recognized and efforts are being made to encourage the release of raw patient-level data from these trials to the public. The issue of sharing clinical trial data has recently gained attention, with many agreeing that this type of data should be made available for research in a timely manner. The availability of clinical trial data is most important for study reproducibility, meta-analyses, and improvement of study design. There is much discussion in the community over key data sharing issues, including the risks this practice holds. However, one aspect that remains to be adequately addressed is that of the accessibility, quality, and usability of the data being shared. Herein, experiences with the two current major platforms used to store and disseminate clinical trial data are described, discussing the issues encountered and suggesting possible solutions. PMID- 26560698 TI - Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice. AB - BACKGROUND: Tumor progression locus 2 (TPL2), a serine-threonine kinase, functions as a critical regulator of inflammatory pathways and mediates oncogenic events. The potential role of Tpl2 in nonalcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) development remains unknown. METHODS: Both wild-type and Tpl2 knockout male mice were initiated by a hepatic carcinogen (diethylnitrosamine, i.p. with a single dose of 25 mg.kg(-1))at 2 weeks of age, and then were given the high carbohydrate diet feeding to induce hepatic steatosis, inflammation, adenoma and HCC for 24 weeks. RESULTS: Tpl2 knockout mice had significantly lower incidences of liver tumor and developed hepatocellular adenoma only, which is contrast to wild-type mice where they all developed HCC. Tpl2 knockout mice had significantly down-regulated phosphorylation of JNK and ERK, and levels of mRNA expression of pro-inflammatory cytokines (Il-1beta, Il-18, Mcp-1 and Nalp3), which correlated with the reduced incidence and number of hepatic inflammatory foci. Furthermore, Tpl2 ablation resulted in decreased hepatic steatosis and expression of de novo lipogenesis related markers (ACC, SCD1, SREBP1C and AKT phosphorylation), as well as reduction of endoplasmic reticulum stress biomarkers PERK and eIF-2a. CONCLUSION: The study revealed for the first time that Tpl2 plays a significant role in promoting HCC development by its pro-inflammatory effect, which suggested that Tpl2 could be a molecular target for HCC prevention. PMID- 26560701 TI - Online communication predicts Belgian adolescents' initiation of romantic and sexual activity. AB - Online communication is associated with offline romantic and sexual activity among college students. Yet, it is unknown whether online communication is associated with the initiation of romantic and sexual activity among adolescents. This two-wave panel study investigated whether chatting, visiting dating websites, and visiting erotic contact websites predicted adolescents' initiation of romantic and sexual activity. We analyzed two-wave panel data from 1163 Belgian adolescents who participated in the MORES Study. We investigated the longitudinal impact of online communication on the initiation of romantic relationships and sexual intercourse using logistic regression analyses. The odds ratios of initiating a romantic relationship among romantically inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites were two to three times larger than those of non-users. Among sexually inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites, the odds ratios of initiating sexual intercourse were two to five times larger than that among non-users, even after a number of other relevant factors were introduced. CONCLUSION: This is the first study to demonstrate that online communication predicts the initiation of offline sexual and romantic activity as early as adolescence. Practitioners and parents need to consider the role of online communication in adolescents' developing sexuality. WHAT IS KNOWN: * Adolescents increasingly communicate online with peers. * Online communication predicts romantic and sexual activity among college students. What is New: * Online communication predicts adolescents' offline romantic activity over time. * Online communication predicts adolescents' offline sexual activity over time. PMID- 26560700 TI - Psychostimulant-Induced Testicular Toxicity in Mice: Evidence of Cocaine and Caffeine Effects on the Local Dopaminergic System. AB - Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology. Mice were injected with a 13-day chronic binge regimen of caffeine (3x5mg/kg), cocaine (3*10mg/kg), or combined administration. Mice treated with cocaine alone or combined with caffeine showed reduced volume of the seminiferous tubule associated to a reduction in the number of spermatogonia. Cocaine-only and combined treatments induced increased lipid peroxidation evaluated by TBARS assay and decreased glutathione peroxidase mRNA expression. Importantly, caffeine cocaine combination potentiated the cocaine-induced germ cell loss, and induced pro-apoptotic BAX protein expression and diminished adenosine receptor A1 mRNA levels. We analyzed markers of dopaminergic function in the testis and detected the presence of tyrosine hydroxylase (TH) in the cytoplasm of androgen-producing Leydig cells, but also in meiotic germs cells within seminiferous tubules. Moreover, using transgenic BAC-Drd1a-tdTomato and D2R-eGFP mice, we report for the first time the presence of dopamine receptors (DRs) D1 and D2 in testicular mouse Leydig cells. Interestingly, the presence of DRD1 was also detected in the spermatogonia nearest the basal lamina of the seminiferous tubules, which did not show TH staining. We observed that psychostimulants induced downregulation of DRs mRNA expression and upregulation of TH protein expression in the testis. These findings suggest a potential role of the local dopaminergic system in psychostimulant-induced testicular pathology. PMID- 26560702 TI - Dry Co-Digestion of Poultry Manure with Agriculture Wastes. AB - This study tested the effect on thermophilic and mesophilic digestion of poultry manure (PM) or treated poultry manure (TPM) by the addition of agriculture wastes (AWS) as a co-substrate under dry conditions. PM was co-digested with a mixture of AWS consisting of coconut waste, cassava waste, and coffee grounds. Results were increased methane content in biogas, with decreased ammonia accumulation and volatile acids. The highest performance occurred under mesophilic conditions, with a 63 and 41.3 % increase in methane production from addition of AWS to TPM (562 vs. 344 mL g VS(-1) from control) and PM (406 vs. 287 mL g VS(-1) from control), respectively. Thermophilic conditions showed lower performance than mesophilic conditions. Addition of AWS increased methane production by 150 and 69.6 % from PM (323.4 vs. 129 mL g VS(-1) from control) and TPM (297.6 vs. 175.5 mL g VS(-1) from control), respectively. In all experiments, 100 % acetate produced was degraded to methane. Maximum ammonia accumulation was lowered to 43.7 % by mixing of AWS (range 5.35-8.55 vs. 7.81-12.28 g N kg(-1) bed). The pH was held at 7.3-8.8, a range suitable for methanogenesis. PMID- 26560703 TI - [Survival benefit from the addition of bevacizumab to first-line radiochemotherapy for the treatment of proneural glioblastoma?]. PMID- 26560704 TI - Whose preferences should be elicited for use in health-care decision-making? A case study using anticoagulant therapy. AB - The question of whose preferences to elicit in health-state valuation has been widely discussed in the literature. The importance of this debate lies in the fact that health-state utility values are used in health technology assessment (HTA); therefore, an individual's preferences can influence decision-making. If preferences differ across groups, making decisions based on one group's preferences may be suboptimal for the other. Preferences for benefits, risks, experiences and health states associated with anticoagulant therapies have been elicited by researchers due to the underutilization of warfarin and the introduction of non-vitamin K antagonist oral anticoagulants. The majority of existing studies elicit preferences from patient populations as opposed to other stakeholders such as the general public. This paper extends the preference debate by using this clinical area as a case study, with a particular focus on HTA guidelines and the recent advocacy of the use of preference information in benefit-risk assessments. PMID- 26560705 TI - Vegetative Propagule Pressure and Water Depth Affect Biomass and Evenness of Submerged Macrophyte Communities. AB - Vegetative propagule pressure may affect the establishment and structure of aquatic plant communities that are commonly dominated by plants capable of clonal growth. We experimentally constructed aquatic communities consisting of four submerged macrophytes (Hydrilla verticillata, Ceratophyllum demersum, Elodea nuttallii and Myriophyllum spicatum) with three levels of vegetative propagule pressure (4, 8 and 16 shoot fragments for communities in each pot) and two levels of water depth (30 cm and 70 cm). Increasing vegetative propagule pressure and decreasing water level significantly increased the growth of the submerged macrophyte communities, suggesting that propagule pressure and water depth should be considered when utilizing vegetative propagules to re-establish submerged macrophyte communities in degraded aquatic ecosystems. However, increasing vegetative propagule pressure and decreasing water level significantly decreased evenness of the submerged macrophyte communities because they markedly increased the dominance of H. verticillata and E. nuttallii, but had little impact on that of C. demersum and M. spicatum. Thus, effects of vegetative propagule pressure and water depth are species-specific and increasing vegetative propagule pressure under lower water level can facilitate the establishment success of submerged macrophyte communities. PMID- 26560706 TI - Intracellular localization of rice stripe virus RNA-dependent RNA polymerase and its interaction with nucleocapsid protein. AB - The RNA-dependent RNA polymerase (RdRp) of rice stripe virus (RSV) is critical for both the transcription and replication of the viral genome. Despite its importance, little is known about how it functions in cells. In the present study, RSV RdRp was split into three pieces, since expression of the full protein could not be achieved. Then, the intracellular localization of these three RdRp fragments and their interactions with nucleocapsid protein (NP) were investigated, which is another viral protein required for viral RNA synthesis. The data showed that all three RdRp fragments displayed punctuate staining patterns in the cytoplasm, and the C-terminal fragment co-localized with NP in the perinuclear region. Both bimolecular fluorescence complementation and co immunoprecipitation experiments demonstrated that of the three RdRp fragments, only the C-terminal fragment could interact with NP. Further analysis using a series of truncated NPs identified the N-terminal 50-amino-acid region within NP as the determinant for its interaction with the C-terminus of RdRp. PMID- 26560708 TI - The crisis in primary care and community and mental health services. PMID- 26560707 TI - Return-to-work intervention for cancer survivors: budget impact and allocation of costs and returns in the Netherlands and six major EU-countries. AB - BACKGROUND: Return-to-work (RTW)-interventions support cancer survivors in resuming work, but come at additional healthcare costs. The objective of this study was to assess the budget impact of a RTW-intervention, consisting of counselling sessions with an occupational physician and an exercise-programme. The secondary objective was to explore how the costs of RTW-interventions and its financial revenues are allocated among the involved stakeholders in several EU countries. METHODS: The budget impact (BI) of a RTW-intervention versus usual care was analysed yearly for 2015-2020 from a Dutch societal- and from the perspective of a large cancer centre. The allocation of the expected costs and financial benefits for each of the stakeholders involved was compared between the Netherlands, Belgium, England, France, Germany, Italy, and Sweden. RESULTS: The average intervention costs in this case were ?1,519/patient. The BI for the Netherlands was ?-14.7 m in 2015, rising to ?-71.1 m in 2020, thus the intervention is cost-saving as the productivity benefits outweigh the intervention costs. For cancer centres the BI amounts to ?293 k in 2015, increasing to ?1.1 m in 2020. Across European countries, we observed differences regarding the extent to which stakeholders either invest or receive a share of the benefits from offering a RTW-intervention. CONCLUSION: The RTW-intervention is cost-saving from a societal perspective. Yet, the total intervention costs are considerable and, in many European countries, mainly covered by care providers that are not sufficiently reimbursed. PMID- 26560709 TI - Inhibition of highly pathogenic porcine reproductive and respiratory syndrome virus replication by recombinant pseudorabies virus-mediated RNA interference in piglets. AB - Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is a variant of porcine reproductive and respiratory syndrome virus (PRRSV) which, in recent years, has caused heavy economic losses to swine-producing areas. Although current vaccines are somewhat prophylactic, they provide only limited protection. Furthermore, there are currently no effective anti-HP-PRRSV drugs. Consequently, it is necessary to develop novel antiviral strategies. In the present study, three recombinant pseudorabies viruses (PRV) expressing siRNAs against the ORF7 of HP-PRRSV strain HN1 (PRV gG-/siRNAN1, PRV gG-/siRNAN2, and PRV gG-/siRNAN3) were evaluated for the inhibition of HP-PRRSV replication. The results indicated that recombinant PRV-mediated siRNA could significantly decrease the replication of traditional PRRSV strain H1 at mRNA and protein levels in Marc-145 cells. Moreover, one recombinant PRV (PRV gG-/siRNAN2) was found to be inhibit the multiplication of HP-PRRSV strain HN1 effectively in Marc 145 cells at both the protein and ORF7 mRNA level. Twenty 21-day-old healthy weaned piglets were divided into four groups of five piglets each. Groups 1 and 2 were injected i.m. with PRV gG-/siRNAN2 and PRV gG-/siRNANeg individually. The piglets in group 3 were challenged with the HP-PRRSV control. After 24h, the piglets in groups 1-3 were challenged i.m. with HP-PRRSV strain HN1, while those in group 4 were i.m. administered with PBS as a negative control. The results showed that HP-PRRSV in serum and lung samples from piglets was effectively inhibited by PRV gG-/siRNAN2. The clinical signs and gross lesions of piglets inoculated with PRV gG-/siRNAN2 were significantly less invasive than those of the PRV gG-/siRNANeg group and HP-PRRSV control group. These results showed that siRNAs mediated by recombinant PRV could effectively suppress HP-PRRSV replication in vitro as well as in vivo. RNAi mediated by recombinant PRV presents a potential novel method to prevent HP-PRRSV infections in swine. However, the protective efficiency of PRV gG-/siRNAN2 should be assessed in a larger number of piglets in future studies. PMID- 26560711 TI - Effect of drying methods on the phenolic content and antioxidant capacity of Brazilian winemaking byproducts and their stability over storage. AB - This work aimed to study the antioxidant capacity by different methods, the total content of polyphenols and the stability over time of dried byproducts from Brazilian hybrids and Vitis vinifera varieties. Oven-dried at 50 degrees C and spray-dried samples were monitored for 90 days of storage. Under testing conditions, BRS Violeta grapes showed the greatest stability and initial high levels of total phenolics and anthocyanins remained almost unchanged until the end of storage period. The same behavior was observed in BRS Violeta freeze-dried skins, seeds and lees (8557, 9520 and 4261 mg GAE/100 g DM, respectively, and 829 and 257 mg mv-3-glc/100 g DM in skin and lees, respectively). In all methodologies tested, BRS Violeta also showed higher values for antioxidant capacity. These results suggest that dried winemaking byproducts can be used as rich sources of polyphenol compounds for industrial extractions with high stability and antioxidant capacity. PMID- 26560712 TI - An overview of tyrosine kinase inhibitors for the treatment of epithelial ovarian cancer. AB - INTRODUCTION: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and the fifth most common cause of cancer-related deaths in women. Initial treatment with surgery and chemotherapy has improved survival significantly. However, the disease progresses or recurs in most patients. Thus, there is an urgent need to develop more effective treatment strategies. AREAS COVERED: This article provides an overview of tyrosine kinase inhibitors (TKIs) for the treatment of EOC, which is based on English peer-reviewed articles on MEDLINE and related abstracts presented at major conferences. The authors highlight the data from the published clinical trials in EOC patients who were treated with TKIs or TKI-based regimens. EXPERT OPINION: EOC is responsive to most chemotherapeutic drugs and/or biological agents and represents an ideal disease model for investigating novel anti-cancer agents. Numerous small-molecule TKIs targeting the VEGFR, PARP, PI3K-AKT-mTOR, MAPK, Src, PKC, Wee1 and HER1/2 signaling pathways are currently being tested in clinical trials. Research is needed for devising regimens combining TKIs with other agents in an optimal timing schedule and for identifying potential biomarkers predictive of response and survival. PMID- 26560713 TI - Tackling Glaucoma from within the Brain: An Unfortunate Interplay of BDNF and TrkB. AB - According to the neurotrophin deprivation hypothesis, diminished retrograde delivery of neurotrophic support during an early stage of glaucoma pathogenesis is one of the main triggers that induce retinal ganglion cell (RGC) degeneration. Therefore, interfering with neurotrophic signaling seems an attractive strategy to achieve neuroprotection. Indeed, exogenous neurotrophin administration to the eye has been shown to reduce loss of RGCs in animal models of glaucoma; however, the neuroprotective effect was mostly insufficient for sustained RGC survival. We hypothesized that treatment at the level of neurotrophin-releasing brain areas might be beneficial, as signaling pathways activated by target-derived neurotrophins are suggested to differ from pathways that are initiated at the soma membrane. In our study, first, the spatiotemporal course of RGC degeneration was characterized in mice subjected to optic nerve crush (ONC) or laser induced ocular hypertension (OHT). Subsequently, the well-known neurotrophin brain derived neurotrophic factor (BDNF) was chosen as the lead molecule, and the levels of BDNF and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), were examined in the mouse retina and superior colliculus (SC) upon ONC and OHT. Both models differentially influenced BDNF and TrkB levels. Next, we aimed for RGC protection through viral vector-mediated upregulation of collicular BDNF, thought to boost the retrograde neurotrophin delivery. Although the previously reported temporary neuroprotective effect of intravitreally delivered recombinant BDNF was confirmed, viral vector-induced BDNF overexpression in the SC did not result in protection of the RGCs in the glaucoma models used. These findings most likely relate to decreased neurotrophin responsiveness upon vector mediated BDNF overexpression. Our results highlight important insights concerning the complexity of neurotrophic factor treatments that should surely be considered in future neuroprotective strategies. PMID- 26560714 TI - Porcine lung mesenchymal stromal cells possess differentiation and immunoregulatory properties. AB - INTRODUCTION: Mesenchymal stem (stromal) cells (MSCs) possess self-renewal, differentiation and immunoregulatory properties, and therefore are being evaluated as cellular therapy for inflammatory and autoimmune diseases, and for tissue repair. MSCs isolated from bone marrow are extensively studied. Besides bone marrow, MSCs have been identified in almost all organs of the body including the lungs. Lung-derived MSCs may be more effective as therapy for lung diseases as compared to bone marrow-derived MSCs. Pigs are similar to humans in anatomy, physiology and immunological responses, and thus may serve as a useful large animal preclinical model to study potential cellular therapy for human diseases. METHODS: We isolated MSCs from the lungs (L-MSCs) of 4-6-week-old germ-free pigs. We determined the self-renewal, proliferation and differentiation potential of L MSCs. We also examined the mechanisms of immunoregulation by porcine L-MSCs. RESULTS: MSCs isolated from porcine lungs showed spindle-shaped morphology and proliferated actively in culture. Porcine L-MSCs expressed mesenchymal markers CD29, CD44, CD90 and CD105 and lacked the expression of hematopoietic markers CD34 and CD45. These cells were multipotent and differentiated into adipocytes, osteocytes and epithelial cells. Like human MSCs, L-MSCs possessed immunoregulatory properties and inhibited proliferation of T cells and interferon gamma and tumor necrosis factor-alpha production by T cells and dendritic cells, respectively, and increased the production of T-helper 2 cytokines interleukin (IL)-4 and IL-13 by T cells. L-MSCs induced the production of prostaglandin E2 (PGE2) in MSC-T cell co-cultures and inhibition of PGE2 significantly restored (not completely) the immune modulatory effects of L-MSCs. CONCLUSIONS: Here, we demonstrate that MSCs can be isolated from porcine lung and that these cells, similar to human lung MSCs, possess in vitro proliferation, differentiation and immunomodulatory functions. Thus, these cells may serve as a model system to evaluate the contribution of lung MSCs in modulating the immune response, interactions with resident epithelial cells and tissue repair in a pig model of human lung diseases. PMID- 26560715 TI - Prediction of cervical lymph node metastasis in patients with papillary thyroid cancer using combined conventional ultrasound, strain elastography, and acoustic radiation force impulse (ARFI) elastography. AB - OBJECTIVES: To investigate the value of combined conventional ultrasound (US), strain elastography (SE) and acoustic radiation force impulse (ARFI) elastography for prediction of cervical lymph node metastasis (CLNM) in papillary thyroid cancer (PTC). METHODS: A consecutive series of 203 patients with 222 PTCs were preoperatively evaluated by US, SE, and ARFI including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ). A multivariate analysis was performed to predict CLNM by 22 independent variables. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. RESULTS: Multivariate analysis demonstrated that VTI area ratio (VAR) > 1 was the best predictor for CLNM, followed by abnormal cervical lymph node (ACLN), capsule contact, microcalcification, capsule involvement, and multiple nodules (all P < 0.05). ROC analyses of these characteristics showed the areas under the curve (Az), sensitivity, and specificity were 0.600-0.630, 47.7 % 93.2 %, and 26.9 %-78.4 % for US, respectively; and they were 0.784, 83.0 %, and 73.9 %, respectively, for VAR > 1. As combination of US characteristics with and without VAR, the Az, sensitivity, and specificity were 0.803 and 0.556, 83.0 % and 100.0 %, and 77.6 % and 11.2 %, respectively (P < 0.001). CONCLUSIONS: ARFI elastography shows superior performance over conventional US, particularly when combined with US, in predicting CLNM in PTC patients. KEY POINTS: * Conventional ultrasound is useful in predicting cervical lymph node metastasis preoperatively. * Virtual touch tissue imaging area ratio is the strongest predicting factor. * Predictive performance is markedly improved by combining ultrasound characteristics with VAR. * Acoustic radiation force impulse elastography may be a promising complementary tool. PMID- 26560716 TI - Vein Diameter on Unenhanced Multidetector CT Predicts Reperfusion of Pulmonary Arteriovenous Malformation after Embolotherapy. AB - OBJECTIVE: To evaluate the value of the diameter of the draining vein of pulmonary arteriovenous malformation (PAVM) on unenhanced chest MDCT in diagnosing reperfusion after percutaneous vaso-occlusion therapy. METHODS: We retrospectively reviewed our long-term experience of patients with hereditary haemorrhagic telangiectasia and selected cases on the following criteria: an initial pulmonary angiogram with embolotherapy of at least one PAVM, a follow-up MDCT examination in the following year followed by a second pulmonary angiogram with embolotherapy if needed. Follow-up unenhanced chest MDCT examinations were analyzed blindly from results of pulmonary artery angiogram and clinical data, the diameter of the efferent vein close to the PAVM sac was measured, then compared to those of pulmonary artery angiogram as a gold standard. RESULTS: Eighty-eight of 100 patients met inclusion criteria, in whom 62 of 176 PAVMs were reperfused at angiogram. The mean diameter of the efferent vein on MDCT was 4.3 +/- 2.1 mm in patent PAVMs and 1.8 +/- 0.9 mm in non-patent PAVMs (p < 0.0001). The optimal cutoff diameter based on ROC analysis was 2.5 mm (sensitivity = 98.4 %; specificity = 87.7 %). CONCLUSION: A diameter of the draining vein of PAVM of 2.5 mm or greater on unenhanced MDCT is a strong predictor of reperfusion. KEY POINTS: * Diameter of draining vein of 2.5 mm or greater is associated with reperfusion. * Unenhanced chest MDCT predicts reperfusion of PAVMs with good sensitivity and specificity. * Unenhanced MDCT can guide a decision of repeat pulmonary angiogram and embolotherapy. * The mean vein diameter change of PAVMs occluded at follow-up is 3.8 mm. * Overall success rate after a median of 6 months embolotherapy was 64.7 %. PMID- 26560717 TI - Organ-based tube current modulation in a clinical context: Dose reduction may be largely overestimated in breast tissue. AB - OBJECTIVES: Organ-based tube current modulation aims to reduce exposure to radiosensitive organs like the breasts by considering their anatomical location and altering tube current during rotation. Former phantom studies demonstrated a dose reduction of 20-37 %. Our study aimed to estimate the potential of dose reduction with this technique in relation to the actual location of breast tissue in a large clinical cohort. METHODS: A 1-year cohort of chest CTs of females (N=1,263) was retrospectively evaluated. To estimate the relative dose effect, breast location was analysed by measuring the angle range of glandular tissue within the different dose zones. Relative exposure compared with constant tube current was calculated. Descriptive statistics and Wilcoxon-test were applied. RESULTS: Only 63 % of angle range of glandular breast tissue was found inside the reduced dose zone. The estimated mean relative dose reduction was lower than observed in former phantom studies(16 % vs. 20-37 %) but still significant compared to constant tube current (p<0.0001). CONCLUSIONS: Although organ-based tube current modulation results in a significant reduction of breast exposure compared to non-modulated irradiation, the technique cannot unfold its full potential, because breast tissue is often located outside the reduced dose zone, resulting in significantly lower dose reduction than expected. KEY POINTS: * OBTCM results in significant dose reduction compared to constant tube current scans. * A substantial portion of glandular tissue lies outside the reduced dose zone. * Potential dose reduction using organ-based tube current modulation may be overestimated. PMID- 26560718 TI - Novel application of chemical shift gradient echo in- and opposed-phase sequences in 3 T MRI for the detection of H-MRS visible lipids and grading of glioma. AB - OBJECTIVES: We evaluated the feasibility of using chemical shift gradient-echo (GE) in- and opposed-phase (IOP) imaging to grade glioma. METHODS: A phantom study was performed to investigate the correlation of (1)H MRS-visible lipids with the signal loss ratio (SLR) obtained using IOP imaging. A cross-sectional study approved by the institutional review board was carried out in 22 patients with different glioma grades. The patients underwent scanning using IOP imaging and single-voxel spectroscopy (SVS) using 3T MRI. The brain spectra acquisitions from solid and cystic components were obtained and correlated with the SLR for different grades. RESULTS: The phantom study showed a positive linear correlation between lipid quantification at 0.9 parts per million (ppm) and 1.3 ppm with SLR (r = 0.79-0.99, p < 0.05). In the clinical study, we found that SLR at the solid portions was the best measure for differentiating glioma grades using optimal cut points of 0.064 and 0.086 with classification probabilities for grade II (SII = 1), grade III (SIII = 0.50) and grade IV (SIV = 0.89). CONCLUSIONS: The results underscore the lipid quantification differences in grades of glioma and provide a more comprehensive characterization by using SLR in chemical shift GE IOP imaging. SLR in IOP sequence demonstrates good performance in glioma grading. KEY POINTS: * Strong correlation was seen between lipid concentration and SLR obtained using IOP * IOP sequence demonstrates significant differences in signal loss within the glioma grades * SLR at solid tumour portions was the best measure for differentiation * This sequence is applicable in a research capacity for glioma staging armamentarium. PMID- 26560719 TI - How often are Patients Harmed When They Visit the Computed Tomography Suite? A Multi-year Experience, in Incident Reporting, in a Large Academic Medical Center. AB - OBJECTIVES: Our goal is to present our multi-year experience in incident reporting in CT in a large medical centre. METHODS: This is an IRB-approved, HIPAA-compliant study. Informed consent was waived for this study. The electronic safety incident reporting system of our hospital was searched for the variables from April 2006 to September 2012. Incident classifications were diagnostic test orders, ID/documentation, safety/security/conduct, service coordination, surgery/procedure, line/tube, fall, medication/IV safety, employee general incident, environment/equipment, adverse drug reaction, skin/tissue and diagnosis/treatment. RESULTS: A total of 1918 incident reports occurred in the study period and 843,902 CT examinations were performed. The rate of safety incident was 0.22 % (1918/843,902). The highest incident rates were due to adverse drug reactions (652/843,902 = 0.077 %) followed by medication/IV safety (573/843,902 = 0.068 %) and diagnostic test orders (206/843,902 = 0.024 %). Overall 45 % of incidents (869/1918) caused no harm and did not affect the patient, 33 % (637/1918) caused no harm but affected the patient, 22 % (420/1918) caused temporary or minor harm/damage and less than 1 % (10/1918) caused permanent or major harm/damage or death. CONCLUSION: Our study shows a total safety incident report rate of 0.22 % in CT. The most common incidents are adverse drug reaction, medication/IV safety and diagnostic test orders. KEY POINTS: * Total safety incident report rate in CT is 0.22 %. * Adverse drug reaction is the most common safety incident in CT. * Medication/IV safety is the second most common safety incident in CT. PMID- 26560720 TI - Incidence and risk factors of early arterial blood flow stasis during first radioembolization of primary and secondary liver malignancy using resin microspheres: an initial single-center analysis. AB - OBJECTIVES: To retrospectively determine incidence of early arterial blood flow stasis and its influencing factors during resin-based radioembolization (RE) of liver tumours. METHODS: Data of patients undergoing resin-based RE from 06/2006 12/2013 were reviewed. Second RE procedures of the same liver lobe were excluded. 90-yttrium dose was calculated according to the body surface area method. Data were categorized according to RE without full dose application because of early stasis and with full dose application. Clinical/procedural characteristics were recorded. Logistic regression was performed to identify associations between clinical/procedural characteristics and early stasis. RESULTS: 362 patients [220 male; mean age 62 years (range 26-90)] underwent 416 RE sessions with early stasis occurring in 103 REs (24.8 %). Highest incidence and degree of stasis were observed in breast cancer metastases [42.6 % (20/47); 55.8 % of mean intended dose administered]. Independent risk factors were: metastasized breast cancer (odds ratio [OR] 2.18, p = 0.02), liver tumour-burden <25 % and 25-50 % (ORs 5.33, 15.64; p < 0.0001), tumour hypovascularity (OR 2.70, p = 0.04), previous bevacizumab therapy (OR 2.79, p = 0.0009) and concurrent chemotherapy (OR 8.69, p < 0.0001). CONCLUSION: Early stasis was observed in 24.8 % of resin-based REs. In the presence of the identified risk factors, extra care should be taken during microsphere administration. KEY POINTS: * Early arterial blood flow stasis is a known problem of resin-based RE. * The study showed that early stasis occurs in 25 % of REs. * Several clinical and procedural factors are associated with early stasis. * In patients at risk extra care should be taken during RE. PMID- 26560721 TI - Prediction of biochemical recurrence after radical prostatectomy with PI-RADS version 2 in prostate cancers: initial results. AB - OBJECTIVES: To determine whether the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) helps predict biochemical recurrence (BCR) after radical prostatectomy for prostate cancer (PCa). METHODS: We included 158 patients with PCa who underwent magnetic resonance imaging (MRI) and radical prostatectomy (RP). Clinical (prostate-specific antigen, greatest percentage of core, and percentage of positive core number), PI-RADSv2 score on MRI, and surgical parameters (Gleason score, extracapsular extension, seminal vesicle invasion, and tumour volume) were investigated. Univariate and multivariate analyses using Cox's proportional hazards model were performed to assess parameters predictive of BCR (two consecutive prostate specific antigens >=0.2 ng/ml). Kaplan-Meier survival curves were analyzed. RESULTS: The rate of BCR was 13.3 % (21/158) after surgery (median follow-up, 25 months; range, 12-36). No subject with a PI-RADS score <4 had BCR. In univariate analysis, all parameters were significant for BCR (p < 0.05), except seminal vesicle invasion (p = 0.254). Meanwhile, PI-RADS score was the only independent parameter for BCR in multivariate analysis (p < 0.05). Two-year, BCR-free survival post-RP was significantly lower for PI-RADS >=4 (84.7 85.5 %) than for PI-RADS <4 (100 %; p < 0.05). CONCLUSION: As a preoperative imaging tool, PI-RADSv2 may be useful to predict BCR after radical prostatectomy for PCa. KEY POINTS: * No subject with PI-RADS <4 had BCR after RP * PI-RADSv2 was the only predictor of BCR in multivariate analysis * Two-year, BCR-free survival following RP was lower for PI-RADS>=4 than for PI-RADS<4 * Inter-rater agreement was good for PI-RADS >=4 or not. PMID- 26560722 TI - Hydrodynamic boost: a novel re-entry technique in subintimal angioplasty of below the-knee vessels. AB - OBJECTIVES: To describe the hydrodynamic boost (HB) technique and report our preliminary results with this technique in the subintimal angioplasty of below the-knee vessels. METHODS: HB was used in 23 cases (14 males, mean age 73 +/- 12 years) of critical limb ischemia, with long chronic total occlusion of tibial arteries extended to the ankle level. The operator performs a manual injection of diluted contrast dye through a 4 F catheter into the subintimal space, close to the patent true distal lumen, in order to achieve a tear in the intimal flap and a connection with the true lumen. RESULTS: In 19/23 (83 %) cases, the HB was effective in creating a connection between the subintimal space and the true distal lumen and it was possible to advance a wire and to conclude the procedure. In 4/23 (17 %) lesions, the HB failed and the procedure was successfully completed by retrograde approach. No major complications occurred. Mean length between catheter tip and re-entry point was 8 +/- 5 mm. CONCLUSIONS: HB seems to be a feasible, safe and effective re-entry technique in distal below-the-knee vessels. This method represents an easy option for re-entry that extends the possibility of antegrade approach to obtain a successful revascularization. KEY POINTS: * In subintimal angioplasty of below-the-knee vessel re-entry can represent a challenge. * Inability to re-enter may determine the failure of the revascularization procedure. * HB is a novel re-entry technique feasible in distal below-the-knee vessels. * HB may increase the success rate of antegrade approach. * In case of failure, retrograde approach remains feasible. PMID- 26560723 TI - Aberrant supracallosal longitudinal bundle: MR features, pathogenesis and associated clinical phenotype. AB - OBJECTIVE: To describe the MRI and structural features of a peculiar malformation of the corpus callosum (CC) in a group of young patients with intellectual disability. METHODS: We studied with conventional MRI and DTI a group of subjects showing an aberrant supracallosal bundle, characterized by the presence of a triangle-shaped bulging above the dorsal surface of CC on the midline. Clinical evaluations, CGH-array and instrumental analysis were also collected. RESULTS: Among 85 patients with malformed CC, we identified 15 subjects that showed the supracallosal bundle. The CC was thickened in five cases, long and thinned in three cases, short and thinned in three cases and it had a "ribbon-like" appearance in four subjects. Additional brain anomalies were present in eight cases. DTI colour maps and tractography showed that the bundle had an antero posterior longitudinal orientation and that the tract bifurcated posteriorly, ending in the posterior hippocampi. Patients had different combinations of neurological symptoms, but all showed mild or severe intellectual disability. CONCLUSIONS: Combining radiological and genetic data with embryological knowledge of the development of cerebral commissures, we hypothesize that the supracallosal bundle represents a vestigial structure, the dorsal fornix, present during fetal life. Its persistence is associated with intellectual disability. KEY POINTS: * An aberrant longitudinal bundle can be detected above corpus callosum. * The presence of the supracallosal bundle is associated with intellectual disability. * The supracallosal bundle may represent a persistent dorsal fornix. PMID- 26560724 TI - 3D non-contrast-enhanced ECG-gated MR angiography of the lower extremities with dual-source radiofrequency transmission at 3.0 T: Intraindividual comparison with contrast-enhanced MR angiography in PAOD patients. AB - OBJECTIVE: To compare prospectively image quality and diagnostic confidence of flow-sensitive 3D turbo spin echo (TSE)-based non-contrast-enhanced MR angiography (NE-MRA) at 3.0 T using dual-source radiofrequency (RF) transmission with contrast-enhanced MRA (CE-MRA) in patients with peripheral arterial occlusive disease (PAOD). METHODS: After consent was obtained, 35 patients (mean age 69.1 +/- 10.6 years) with PAOD stage II-IV underwent NE-MRA followed by CE MRA. Signal-to-noise ratio and contrast-to-noise ratio were calculated. Subjective image quality was independently assessed by two radiologists and stenosis scoring was performed in 875 arterial segments. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for stenosis classification were calculated using CE-MRA as a reference method. Diagnostic agreement with CE-MRA was evaluated with Cohen's kappa statistics. RESULTS: NE-MRA provided high objective and subjective image quality at all levels of the arterial tree. Sensitivity and specificity for the detection of relevant stenosis was 91 % and 89 %, respectively; the NPV was 96 % and the PPV 78 %. There was good concordance between CE-MRA and NE-MRA in stenosis scoring. CONCLUSIONS: 3D electrocardiography (ECG)-gated TSE NE-MRA with patient-adaptive dual-source RF transmission at 3.0 T is a promising alternative for PAOD patients with contraindications for gadolinium-based contrast agents. It offers high sensitivity and NPV values in the detection of clinically relevant arterial stenosis. KEY POINTS: * Flow-sensitive TSE NE-MRA is a promising technique for PAOD evaluation. * Diagnostic accuracy is comparable to contrast-enhanced MRA. * NE-MRA eliminates the risk of NSF in patients with renal insufficiency. * Costs arising from the use of contrast agents can be avoided. PMID- 26560725 TI - Back to the future: sagittal CT in the evaluation of COPD. AB - OBJECTIVES: To identify features of obstructive airway disease on sagittal reconstruction, compare the accuracy of findings to traditional imaging characteristics of COPD, and determine the fraction of additional cases identified using new characteristics. METHODS: The study was approved by the centre's Institutional Review Board and is HIPAA compliant. Two hundred sixteen patients with HRCT and spirometry within a 3-month window were included. Four radiologists evaluated each HRCT for traditional characteristics of COPD and new quantitative and qualitative features of obstruction on axial and sagittal reconstructions. Imaging characteristics were assessed for correlation with the spirometric diagnosis of obstructive airway disease. RESULTS: Quantitative and qualitative findings on sagittal reconstruction are highly specific for COPD (specificity >90 %). Features of hyperinflation on sagittal reconstruction are more accurate predictors of obstruction than traditional axial measures, with greater interobserver reliability (hyperinflation left hemidiaphragm: accuracy: 70.08 % +/- 2.49 %; kappa: 0.511 versus traditional measures: accuracy: 62.00 % +/- 5.38 %; kappa: 0.407). Sagittal reconstruction identified 27-70 % more patients with COPD than traditional axial findings (p < 0.05). CONCLUSIONS: Analysis of sagittal reconstruction enables greater accuracy and specificity in the diagnosis of obstructive airway disease compared to traditional measures on axial imaging. Use of sagittal reconstructions can help identify up to 70 % more patients with COPD than traditional imaging findings alone. KEY POINTS: * HRCT sagittal reconstruction is useful in the evaluation of obstructive lung disease. * Findings on sagittal reconstructions allow physicians to more accurately diagnose COPD. * Routine use of sagittal reconstructions increases the sensitivity for diagnosing COPD. PMID- 26560726 TI - Third-generation dual-source CT of the neck using automated tube voltage adaptation in combination with advanced modeled iterative reconstruction: evaluation of image quality and radiation dose. AB - PURPOSE: To evaluate image quality and radiation dose in third-generation dual source computed tomography (DSCT) of the neck using automated tube voltage adaptation (TVA) with advanced modelled iterative reconstruction (ADMIRE) algorithm. METHODS: One hundred and sixteen patients were retrospectively evaluated. Group A (n = 59) was examined on second-generation DSCT with automated TVA and filtered back projection. Group B (n = 57) was examined on a third generation DSCT with automated TVA and ADMIRE. Age, body diameter, attenuation of several anatomic structures, noise, signal-to-noise ratio (SNR), contrast-to noise ratio (CNR), radiation dose (CTDIvol) and size-specific dose estimates (SSDE) were assessed. Diagnostic acceptability was rated by three readers. RESULTS: Age (p = 0.87) and body diameter (p = 0.075) did not differ significantly. Tube voltage in Group A was set automatically to 100 kV for all patients (n = 59), and to 70 kV (n = 2), 80 kV (n = 5), and 90 kV (n = 50) in Group B. Noise was reduced and CNR was increased significantly (p < 0.001). Diagnostic acceptability was rated high in both groups, with better ratings in Group B (p < 0.001). SSDE was reduced by 34 % in Group B (20.38 +/- 1.63 mGy vs. 13.04 +/- 1.50 mGy, p < 0.001). CONCLUSION: Combination of automated TVA and ADMIRE in neck CT using third-generation DSCT results in a substantial radiation dose reduction with low noise and increased CNR. KEY POINTS: * Third-generation DSCT provides automated tube voltage adaptation with an increment of 10 kV. * 10 kV increment optimizes scans to the patient's neck anatomy. * TVA combined with ADMIRE significantly lower radiation dose in contrast-enhanced neck CT. * TVA in combination with ADMIRE reduces noise and increases SNR and CNR. * Image analysis quoted less noise and better diagnostic acceptability in third-generation DSCT. PMID- 26560727 TI - The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial. AB - OBJECTIVES: To characterize a radiogenomic risk score (RRS), a previously defined biomarker, and to evaluate its potential for stratifying radiological progression free survival (rPFS) in patients with metastatic renal cell carcinoma (mRCC) undergoing pre-surgical treatment with bevacizumab. METHODOLOGY: In this IRB approved study, prospective imaging analysis of the RRS was performed on phase II clinical trial data of mRCC patients (n = 41) evaluating whether patient stratification according to the RRS resulted in groups more or less likely to have a rPFS to pre-surgical bevacizumab prior to cytoreductive nephrectomy. Survival times of RRS subgroups were analyzed using Kaplan-Meier survival analysis. RESULTS: The RRS is enriched in diverse molecular processes including drug response, stress response, protein kinase regulation, and signal transduction pathways (P < 0.05). The RRS successfully stratified rPFS to bevacizumab based on pre-treatment computed tomography imaging with a median progression-free survival of 6 versus >25 months (P = 0.005) and overall survival of 25 versus >37 months in the high and low RRS groups (P = 0.03), respectively. Conventional prognostic predictors including the Motzer and Heng criteria were not predictive in this cohort (P > 0.05). CONCLUSIONS: The RRS stratifies rPFS to bevacizumab in patients from a phase II clinical trial with mRCC undergoing cytoreductive nephrectomy and pre-surgical bevacizumab. KEY POINTS: * The RRS SOMA stratifies patient outcomes in a phase II clinical trial. * RRS stratifies subjects into prognostic groups in a discrete or continuous fashion. * RRS is biologically enriched in diverse processes including drug response programs. PMID- 26560728 TI - Low contrast media volume in pre-TAVI CT examinations. AB - PURPOSE: To evaluate image quality using reduced contrast media (CM) volume in pre-TAVI assessment. METHODS: Forty-seven consecutive patients referred for pre TAVI examination were evaluated. Patients were divided into two groups: group 1 BMI < 28 kg/m(2) (n = 29); and group 2 BMI > 28 kg/m(2) (n = 18). Patients received a combined scan protocol: retrospective ECG-gated helical CTA of the aortic root (80kVp) followed by a high-pitch spiral CTA (group 1: 70 kV; group 2: 80 kVp) from aortic arch to femoral arteries. All patients received one bolus of CM (300 mgI/ml): group 1: volume = 40 ml; flow rate = 3 ml/s, group 2: volume = 53 ml; flow rate = 4 ml/s. Attenuation values (HU) and contrast-to-noise ratio (CNR) were measured at the levels of the aortic root (helical) and peripheral arteries (high-pitch). Diagnostic image quality was considered sufficient at attenuation values > 250HU and CNR > 10. RESULTS: Diagnostic image quality for TAVI measurements was obtained in 46 patients. Mean attenuation values and CNR (HU +/- SD) at the aortic root (helical) were: group 1: 381 +/- 65HU and 13 +/- 8; group 2: 442 +/- 68HU and 10 +/- 5. At the peripheral arteries (high-pitch), mean values were: group 1: 430 +/- 117HU and 11 +/- 6; group 2: 389 +/- 102HU and 13 +/- 6. CONCLUSION: CM volume can be substantially reduced using low kVp protocols, while maintaining sufficient image quality for the evaluation of aortic root and peripheral access sites. KEY POINTS: * Image quality could be maintained using low kVp scan protocols. * Low kVp protocols reduce contrast media volume by 34-67 %. * Less contrast media volume lowers the risk of contrast induced nephropathy. PMID- 26560729 TI - Cross-national comparison of screening mammography accuracy measures in U.S., Norway, and Spain. AB - OBJECTIVE: To compare accuracy measures for mammographic screening in Norway, Spain, and the US. METHODS: Information from women aged 50-69 years who underwent mammographic screening 1996-2009 in the US (898,418 women), Norway (527,464), and Spain (517,317) was included. Screen-detected cancer, interval cancer, and the false-positive rates, sensitivity, specificity, positive predictive value (PPV) for recalls (PPV-1), PPV for biopsies (PPV-2), 1/PPV-1 and 1/PPV-2 were computed for each country. Analyses were stratified by age, screening history, time since last screening, calendar year, and mammography modality. RESULTS: The rate of screen-detected cancers was 4.5, 5.5, and 4.0 per 1000 screening exams in the US, Norway, and Spain respectively. The highest sensitivity and lowest specificity were reported in the US (83.1 % and 91.3 %, respectively), followed by Spain (79.0 % and 96.2 %) and Norway (75.5 % and 97.1 %). In Norway, Spain and the US, PPV-1 was 16.4 %, 9.8 %, and 4.9 %, and PPV-2 was 39.4 %, 38.9 %, and 25.9 %, respectively. The number of women needed to recall to detect one cancer was 20.3, 6.1, and 10.2 in the US, Norway, and Spain, respectively. CONCLUSIONS: Differences were found across countries, suggesting that opportunistic screening may translate into higher sensitivity at the cost of lower specificity and PPV. KEY POINTS: * Positive predictive value is higher in population-based screening programmes in Spain and Norway. * Opportunistic mammography screening in the US has lower positive predictive value. * Screening settings in the US translate into higher sensitivity and lower specificity. * The clinical burden may be higher for women screened opportunistically. PMID- 26560730 TI - Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition. AB - OBJECTIVES: To validate a visual rating scale of frontal atrophy with quantitative imaging and study its association with clinical status, APOE epsilon4, CSF biomarkers, and cognition. METHODS: The AddNeuroMed and ADNI cohorts were combined giving a total of 329 healthy controls, 421 mild cognitive impairment patients, and 286 Alzheimer's disease (AD) patients. Thirty-four patients with frontotemporal dementia (FTD) were also included. Frontal atrophy was assessed with the frontal sub-scale of the global cortical atrophy scale (GCA F) on T1-weighted images. Automated imaging markers of cortical volume, thickness, and surface area were evaluated. Manual tracing was also performed. RESULTS: The GCA-F scale reliably reflects frontal atrophy, with orbitofrontal, dorsolateral, and motor cortices being the regions contributing most to the GCA-F ratings. GCA-F primarily reflects reductions in cortical volume and thickness, although it was able to detect reductions in surface area too. The scale showed significant associations with clinical status and cognition. CONCLUSION: The GCA F scale may have implications for clinical practice as supportive diagnostic tool for disorders demonstrating predominant frontal atrophy such as FTD and the executive presentation of AD. We believe that GCA-F is feasible for use in clinical routine for the radiological assessment of dementia and other disorders. KEY POINTS: * The GCA-F visual rating scale reliably reflects frontal brain atrophy. * Orbitofrontal, dorsolateral, and motor cortices are the most contributing regions. * GCA-F shows significant associations with clinical status and cognition. * GCA-F may be supportive diagnostic tool for disorders demonstrating predominant frontal atrophy. * GCA-F may be feasible for use in radiological routine. PMID- 26560731 TI - Dual time point imaging for F18-FDG-PET/CT does not improve the accuracy of nodal staging in non-small cell lung cancer patients. AB - OBJECTIVES: To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC). METHODS: This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of flight). LN uptake in PET was assessed visually (four-step score) and semi quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Delta-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses. RESULTS: Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Delta-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5-92.9%) and delayed PET (range, 85.2-92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5 92.3%). CONCLUSIONS: Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET based LN staging. Dedicated visual assessment criteria performed very well. KEY POINTS: * DTPI did not improve accuracy of PET-based LN staging in NSCLC. * Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. * A four-step visual score may allow highly accurate, standardized LN assessment. PMID- 26560732 TI - Computer tomography colonography participation and yield in patients under surveillance for 6-9 mm polyps in a population-based screening trial. AB - PURPOSE: Surveillance CT colonography (CTC) is a viable option for 6-9 mm polyps at CTC screening for colorectal cancer. We established participation and diagnostic yield of surveillance and determined overall yield of CTC screening. MATERIAL AND METHODS: In an invitational CTC screening trial 82 of 982 participants harboured 6-9 mm polyps as the largest lesion(s) for which surveillance CTC was advised. Only participants with one or more lesion(s) >=6 mm at surveillance CTC were offered colonoscopy (OC); 13 had undergone preliminary OC. The surveillance CTC yield was defined as the number of participants with advanced neoplasia in the 82 surveillance participants, and was added to the primary screening yield. RESULTS: Sixty-five of 82 participants were eligible for surveillance CTC of which 56 (86.2 %) participated. Advanced neoplasia was diagnosed in 15/56 participants (26.8 %) and 9/13 (69.2 %) with preliminary OC. Total surveillance yield was 24/82 (29.3 %). No carcinomas were detected. Adding surveillance results to initial screening CTC yield significantly increased the advanced neoplasia yield per 100 CTC participants (6.1 to 8.6; p < 0.001) and per 100 invitees (2.1 to 2.9; p < 0.001). CONCLUSION: Surveillance CTC for 6-9 mm polyps has a substantial yield of advanced adenomas and significantly increased the CTC yield in population screening. KEY POINTS: * The participation rate in surveillance CT colonography (CTC) is 86 %. * Advanced adenoma prevalence in a 6 9 mm CTC surveillance population is high. * Surveillance CTC significantly increases the yield of population screening by CTC. * Surveillance CTC for 6-9 mm polyps is a safe strategy. * Surveillance CTC is unlikely to yield new important extracolonic findings. PMID- 26560733 TI - Portrayal of radiology in a major medical television series: How does it influence the perception of radiology among patients and radiology professionals? AB - OBJECTIVES: To assess how the portrayal of Radiology on medical TV shows is perceived by patients and radiology professionals. METHODS: In this IRB-approved study with patient consent waived, surveys were conducted among adult patients scheduled for radiological examinations and radiology professionals. The questionnaire investigated medical TV watching habits including interest in medical TV shows, appearance of radiological examination/staff, radiology's role in diagnosis-making, and rating of the shows' accuracy in portraying radiology relative to reality. RESULTS: One hundred and twenty-six patients and 240 professionals (133 technologists, 107 radiologists) participated. 63.5 % patients and 63.2 % technologists rated interest in medical TV shows >=5 (scale 1-10) versus 38.3 % of radiologists. All groups noted regular (every 2nd/3rd show) to >1/show appearance of radiological examinations in 58.5-88.2 % compared to 21.0 46.2 % for radiological staff appearance. Radiology played a role in diagnosis making regularly to >1/show in 45.3-52.6 %. There is a positive correlation for interest in medical TV and the perception that radiology is accurately portrayed for patients (r = 0.49; P = 0.001) and technologists (r = 0.38; P = 0.001) but not for radiologists (r = 0.01). CONCLUSIONS: The majority of patients perceive the portrayed content as accurate. Radiologists should be aware of this cultivation effect to understand their patients' behaviour which may create false expectations towards radiological examinations and potential safety hazards. KEY POINTS: * Radiology in medical TV shows is conveyed as important in diagnosis making * Presence of radiological staff is less frequent compared to examinations shown * Positive correlation for interest in medical TV and radiology perceived as accurate * TV experience may create false expectations and potential safety hazards. PMID- 26560735 TI - Update on the use of meningococcal serogroup C CRM197-conjugate vaccine (Meningitec) against meningitis. AB - Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec. PMID- 26560736 TI - The Value of Psychiatric Diagnoses. PMID- 26560734 TI - Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease: A prospective study. AB - Magnetic resonance elastography (MRE), an advanced magnetic resonance-based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head-to-head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head-to-head for diagnosing fibrosis in well-characterized patients with biopsy-proven NAFLD. This cross-sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (+/- standard deviation) age and body mass index were 48.9 (+/-15.4) years and 31.8 (+/-7.0) kg/m(2) , respectively. For diagnosing any fibrosis (>= stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723-0.875), significantly (P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568-0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (P < 0.001) but not in nonobese patients (P = 0.722). The MRE AUROCs for diagnosing >=stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816-0.953), 0.934 (95% CI 0.863-1.000), and 0.882 (95% CI 0.729-1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776-0.921), 0.896 (95% CI 0.824-0.968), and 0.862 (95% CI 0.721 1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. CONCLUSION: MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. PMID- 26560737 TI - Automatic Fall Detection System Based on the Combined Use of a Smartphone and a Smartwatch. AB - Due to their widespread popularity, decreasing costs, built-in sensors, computing power and communication capabilities, Android-based personal devices are being seen as an appealing technology for the deployment of wearable fall detection systems. In contrast with previous solutions in the existing literature, which are based on the performance of a single element (a smartphone), this paper proposes and evaluates a fall detection system that benefits from the detection performed by two popular personal devices: a smartphone and a smartwatch (both provided with an embedded accelerometer and a gyroscope). In the proposed architecture, a specific application in each component permanently tracks and analyses the patient's movements. Diverse fall detection algorithms (commonly employed in the literature) were implemented in the developed Android apps to discriminate falls from the conventional activities of daily living of the patient. As a novelty, a fall is only assumed to have occurred if it is simultaneously and independently detected by the two Android devices (which can interact via Bluetooth communication). The system was systematically evaluated in an experimental testbed with actual test subjects simulating a set of falls and conventional movements associated with activities of daily living. The tests were repeated by varying the detection algorithm as well as the pre-defined mobility patterns executed by the subjects (i.e., the typology of the falls and non-fall movements). The proposed system was compared with the cases where only one device (the smartphone or the smartwatch) is considered to recognize and discriminate the falls. The obtained results show that the joint use of the two detection devices clearly increases the system's capability to avoid false alarms or 'false positives' (those conventional movements misidentified as falls) while maintaining the effectiveness of the detection decisions (that is to say, without increasing the ratio of 'false negatives' or actual falls that remain undetected). PMID- 26560738 TI - Chemoproteomic Approach to Explore the Target Profile of GPCR ligands: Application to 5-HT1A and 5-HT6 Receptors. AB - Determination of the targets of a compound remains an essential aspect in drug discovery. A complete understanding of all binding interactions is critical to recognize in advance both therapeutic effects and undesired consequences. However, the complete polypharmacology of many drugs currently in clinical development is still unknown, especially in the case of G protein-coupled receptor (GPCR) ligands. In this work we have developed a chemoproteomic platform based on the use of chemical probes to explore the target profile of a compound in biological systems. As proof of concept, this methodology has been applied to selected ligands of the therapeutically relevant serotonin 5-HT1A and 5-HT6 receptors, and we have identified and validated some of their off-targets. This approach could be extended to other drugs of interest to study the targeted proteome in disease-relevant systems. PMID- 26560739 TI - Adjuvant corticosteroids for reducing death in neonatal bacterial meningitis. AB - BACKGROUND: Bacterial meningitis remains a significant cause of neonatal and childhood morbidity and mortality in many countries of the world, particularly in developing countries. In some instances, children recover but remain impaired as a result of neurological sequelae such as hearing loss, developmental delay and cognitive impairment. OBJECTIVES: To assess the effectiveness and safety of adjunctive corticosteroids in reducing death and neurological sequelae in neonates with bacterial meningitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7), MEDLINE via PubMed (1966 to July 2015), African Index Medicus (up to January 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (up to July 2015), EMBASE (up to July 2015) and the metaRegister of Controlled Trials (mRCT) for ongoing trials. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of adjunctive corticosteroids for treatment of neonates with bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed and extracted data on methods, participants, interventions and outcomes (all-cause death until hospital discharge, presence of sensorineural deafness at one year and presence of neurological deficits or developmental delay at two years, adverse events). Risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) were calculated when appropriate. We assessed quality using the Cochrane risk of bias assessment tool and the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system. MAIN RESULTS: We found two trials with 132 participants that met our inclusion criteria. One of the included trials was a quasi-randomised trial.Adjunctive corticosteroids reduced the risk of death (typical RR 0.46, 95% confidence interval (CI) 0.24 to 0.88; typical RD -0.19, 95% CI -0.33 to -0.04; NNTB = 6; two studies, 132 participants, very low-quality evidence) but did not have a significant effect on the number of infants with sensorineural deafness at two years (RR 1.80, 95% CI 0.18 to 18.21; RD 0.04, 95% CI -0.12 to 0.21; one study, 38 participants, low-quality evidence). In one trial, dexamethasone reduced the likelihood of hearing loss at four to 10 weeks post discharge (RR 0.41, 95% CI 0.17 to 0.98; RD -0.25, 95% CI -0.48 to -0.01; one study, 59 participants, low quality evidence). Data reported on the other outcomes of interest were insufficient. AUTHORS' CONCLUSIONS: Very low-quality data from two randomised controlled trials suggest that some reduction in death and hearing loss may result from use of adjunctive steroids alongside standard antibiotic therapy for treatment of patients with neonatal meningitis. Benefit is not yet seen with regards to reduction in neurological sequelae. Researchers who wish to clarify these findings must conduct more robustly designed trials with greater numbers of participants, evaluating more relevant outcomes and providing adequate follow-up. PMID- 26560740 TI - Sensitivity of the Balance Error Scoring System and the Sensory Organization Test in the Combat Environment. AB - This study evaluated the utility of the Balance Error Scoring System (BESS) and the Sensory Organization Test (SOT) as tools for the screening and monitoring of Service members (SMs) with mild traumatic brain injury (mTBI) in a deployed setting during the acute and subacute phases of recovery. Patient records (N = 699) were reviewed for a cohort of SMs who sustained a blast-related mTBI while deployed to Afghanistan and were treated at the Concussion Restoration Care Center (CRCC) at Camp Leatherneck. On initial intake into the CRCC, participants completed two assessments of postural control, the BESS, and SOT. SMs with mTBI performed significantly worse on the BESS and SOT when compared with comparative samples. When the SOT data were further examined using sensory ratios, the results indicated that postural instability was primarily a result of vestibular and visual integration dysfunction (r > 0.62). The main finding of this study was that the sensitivity of the SOT composite score (50-58%) during the acute phase was higher than previous sensitivities found in the sports medicine literature for impact-related trauma. PMID- 26560741 TI - Determination of RNA polymerase binding surfaces of transcription factors by NMR spectroscopy. AB - In bacteria, RNA polymerase (RNAP), the central enzyme of transcription, is regulated by N-utilization substance (Nus) transcription factors. Several of these factors interact directly, and only transiently, with RNAP to modulate its function. As details of these interactions are largely unknown, we probed the RNAP binding surfaces of Escherichia coli (E. coli) Nus factors by nuclear magnetic resonance (NMR) spectroscopy. Perdeuterated factors with [(1)H,(13)C] labeled methyl groups of Val, Leu, and Ile residues were titrated with protonated RNAP. After verification of this approach with the N-terminal domain (NTD) of NusG and RNAP we determined the RNAP binding site of NusE. It overlaps with the NusE interaction surface for the NusG C-terminal domain, indicating that RNAP and NusG compete for NusE and suggesting possible roles for the NusE:RNAP interaction, e.g. in antitermination and direct transcription:translation coupling. We solved the solution structure of NusA-NTD by NMR spectroscopy, identified its RNAP binding site with the same approach we used for NusG-NTD, and here present a detailed model of the NusA-NTD:RNAP:RNA complex. PMID- 26560742 TI - Medical Gains of Chondroitin Sulfate Upon Fucosylation. AB - Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) composed of alternating N acetyl galactosamine and glucuronic acid units within disaccharide building blocks. CS is a key functional component in proteoglycans of cartilaginous tissues. Owing to its numerous biological roles, CS is widely explored in the pharmaceutical market as nutraceutical ingredient commonly utilized against arthritis, osteoarthrosis, and sometimes osteoporosis. Tissues like shark cartilage and bovine trachea are common sources of CS. Nonetheless, a new CS type has been introduced and investigated in the last few decades in what regards its medical potentials. It is named fucosylated chondroitin sulfate (FucCS). This less common CS type is isolated exclusively from the body wall of sea cucumbers. The presence of fucosyl branching units in the holothurian FucCS gives to this unique GAG, therapeutic properties in various pathophysiological systems which are inexistent in the common CS explored in the market. Examples of these systems are coagulation, thrombosis, hemodialysis, atherosclerosis, cellular growth, angiogenesis, fibrosis, tumor growth, inflammation, viral and protozoan infections, hyperglycemia, diabetes-related pathological events and tissue damage. This report aims at describing the medical benefits gained upon fucosylation of CS. Clinical prospects of these medical benefits are also discussed herein. PMID- 26560743 TI - Etiology of Pervasive Versus Situational Antisocial Behaviors: A Multi-Informant Longitudinal Cohort Study. AB - The aim of this study was to disentangle pervasive from situational antisocial behaviors using multiple informants, and to investigate their genetic and environmental etiologies in preadolescence and across time. Antisocial behaviors were assessed in 2,232 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study at ages 5 and 12. Pervasive antisocial behaviors were defined as behaviors that mothers, teachers, interviewers, and twins themselves agreed on. Results from a psychometric model indicated that the variation in children's pervasive antisocial behaviors was mostly accounted for by familial influences that originated in childhood, whereas situational behaviors were explained by newly emerging nonshared environmental and genetic influences. This study shows that children's pervasive and situational antisocial behaviors have distinct etiologies that could guide research and treatment. PMID- 26560744 TI - Raster-scanned intensity-controlled carbon ion therapy for mucosal melanoma of the paranasal sinus. AB - BACKGROUND: The purpose of this study was to evaluate the use of raster-scanned intensity-controlled carbon ion therapy (ICCT) in the treatment of mucosal melanoma of the paranasal sinus. METHODS: Patients received combined intensity modulated radiotherapy (IMRT) plus carbon ion (C12). Records of 18 consecutive patients treated between 2009 and 2013 were analyzed retrospectively regarding toxicity (Common Terminology Criteria for Adverse Events, version 4), treatment response (Response Evaluation Criteria in Solid Tumors [RECIST]), and control/survival rates. RESULTS: Most patients had advanced disease (T4, 94%; gross residual disease, 78%). Median dose was 74 GyE (median boost volume = 157 mL). C12 treatments were planned as ICCT, no concurrent chemotherapy was administered. Grade III or higher late toxicity was not observed. Overall survival (OS), progression-free survival (PFS), and locoregional control at 3 years were 16.2%, 0%, and 58.3%, respectively (median follow-up, 18 months). Resection status did not impact locoregional control or survival rates. CONCLUSION: ICCT results in promising locoregional control at mild toxicity. OS is poor because of the occurrence of distant metastases; therefore, addition of systemic components to primary treatment should be investigated. (c) 2015 Wiley Periodicals, Head Neck 38: E1445-E1451, 2016. PMID- 26560746 TI - Continuous infusion of factor VIII concentrates in obese patients with severe haemophilia A: is weight-based dose-adjustment required? PMID- 26560747 TI - Applause sign: screening utility for dementia and cognitive impairment. AB - OBJECTIVE: To examine the diagnostic utility of applause sign scores for the diagnosis of dementia and mild cognitive impairment. METHODS: Consecutive unselected new outpatient referrals to a dedicated cognitive disorders clinic over a 12-month period were administered the clapping test. Criterion diagnosis was by usual clinic assessment using standard diagnostic criteria, blind to applause sign score. RESULTS: Applause sign scores differed significantly (p < 0.001) between diagnostic groups (dementia, mild cognitive impairment, subjective memory complaint) and did not correlate with other cognitive screening instrument scores. Nearly three-quarters of those with an abnormal score had cognitive impairment. Applause sign score was specific but not sensitive for a diagnosis of cognitive impairment. CONCLUSION: The applause sign supports a diagnosis of dementia or cognitive impairment in high prevalence settings and may be useful in conjunction with other cognitive screening tests. PMID- 26560745 TI - Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents. AB - Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID- 26560748 TI - Functional Neuroimaging in Psychopathy. AB - BACKGROUND AND AIM: Psychopathy is associated with cognitive and affective deficits causing disruptive, harmful and selfish behaviour. These have considerable societal costs due to recurrent crime and property damage. A better understanding of the neurobiological bases of psychopathy could improve therapeutic interventions, reducing the related social costs. To analyse the major functional neural correlates of psychopathy, we reviewed functional neuroimaging studies conducted on persons with this condition. METHODS: We searched the PubMed database for papers dealing with functional neuroimaging and psychopathy, with a specific focus on how neural functional changes may correlate with task performances and human behaviour. RESULTS: Psychopathy-related behavioural disorders consistently correlated with dysfunctions in brain areas of the orbitofrontal-limbic (emotional processing and somatic reaction to emotions; behavioural planning and responsibility taking), anterior cingulate-orbitofrontal (correct assignment of emotional valence to social stimuli; violent/aggressive behaviour and challenging attitude) and prefrontal-temporal-limbic (emotional stimuli processing/response) networks. Dysfunctional areas more consistently included the inferior frontal, orbitofrontal, dorsolateral prefrontal, ventromedial prefrontal, temporal (mainly the superior temporal sulcus) and cingulated cortices, the insula, amygdala, ventral striatum and other basal ganglia. CONCLUSIONS: Emotional processing and learning, and several social and affective decision-making functions are impaired in psychopathy, which correlates with specific changes in neural functions. PMID- 26560749 TI - Rate of employment after liver transplantation in France: a single-centre study. AB - BACKGROUND: A return to gainful employment is an important outcome parameter after liver transplantation (LT). A recent study in the USA has shown a very high rate of unemployment after LT (75%). To date, there are no available data in France, where the public health insurance programme guarantees financial protection for everyone. AIMS: The aim of this study was to assess the employment rate after LT in a French LT centre and to determine factors associated with employment after LT. METHODS: All patients who had undergone liver transplantation at our centre between January 2000 and April 2011 and who met the following criteria responded to a questionnaire: (i) between 18 and 65 years old at the time of LT, (ii) alive 1 year after LT, (iii) alive, not retired and released from the hospital at the time of survey, (iv) French residents who were affiliated with French national health insurance. RESULTS: A total of 345 LTs were performed in 314 patients during the study period. Of the patients, 109 were excluded from the study: 23 had died within the first year after LT, 28 had died at the time of the survey, three were still in the hospital, seven were living in a foreign country, 11 had retired and 37 were older than 65 years after LT. Two hundred five patients were included in the study. The response rate was 76.6% (157/205). Patients responded a mean 6.1 +/- 0.9 years after LT, 77.7% were French nationals, 73.2% were men, and the mean age at LT was 48.8 +/- 9.9 years. The aetiologies of liver disease were as follows: alcohol 32.5%, hepatitis C 26.1%, alcohol and hepatitis C 3.8%, hepatitis B 15.3%, biliary cirrhosis 5.1%, autoimmune 2.5% and other causes 14.7%. Two years after LT, 43.3% of patients were employed. The demographic variables associated with post-LT employment were male sex (P<0.001), age under 40 years at LT (P=0.02), a sedentary job (P=0.007), raising children under the age of 18 years at the time of LT (P=0.01), a high level of education (P=0.001), not being affiliated with the French universal health coverage or 'CMU' (P=0.001). Only 53.3% of the patients who did not return to work after LT stated that they felt like they had a physical disability. CONCLUSION: The rate of return to work after LT in France was 43.1%, which was higher than that reported in the US study. However, this rate remains low and policies supporting return to work are needed to help liver recipients who wish to work after LT. PMID- 26560750 TI - Chronic hepatitis C: treat or wait? A prospective study on reasons for treatment or nontreatment in the era of first-generation protease inhibitors. AB - BACKGROUND AND AIMS: In many countries, current treatment for patients with chronic hepatitis C involves a combination of peginterferon and ribavirin, associated with a protease inhibitor for hepatitis C virus genotype 1. More recent and efficient less toxic antiviral treatments are now available for some patients. Thus, the decision to treat or to wait is challenging. The aims of this study were to: (a) estimate the proportion of treated patients, (b) evaluate the reasons for this decision, and (c) examine the patients' points-of-view in treatment decision. METHODS: This was a prospective study conducted at three French referral centers between March and June 2013. Epidemiological and virological data, reasons for treatment or nontreatment, and data on the doctors' and patients' choices were collected. RESULTS: A total of 255 patients were analyzed. Only 52.6% of patients with fibrosis of 2 or higher were treated. Treatment uptake was reduced in the following groups: previously treated patients, those with poor tolerance during prior treatment, those with heavy alcohol consumption, and those with hepatocellular carcinoma. Of the cirrhotic patients, 55% were not treated: 51.1% had a contraindication, 22.2% had a previous nonresponse. When treatment was refused by the patient, fear of side effects and professional problems were the most frequently cited reasons (90 and 40%, respectively). CONCLUSION: Patients were treated primarily according to consensus guidelines. However, only 45% of cirrhotic patients were treated. In 7.6% of the cases, the patient refused therapy. This study enabled us to measure the importance of patient choice in medical decision-making. Well-informed patients expected not only more efficient but also well-tolerated therapy. PMID- 26560751 TI - Factors related to increased resting energy expenditure in men with liver cirrhosis. AB - OBJECTIVE: Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. PATIENTS AND METHODS: We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. RESULTS: REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, beta-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P<0.05), nonprotein respiratory quotient (P<0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P<0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. CONCLUSION: Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice. PMID- 26560752 TI - How psychosocial factors affect well-being of practice assistants at work in general medical care?--a questionnaire survey. AB - BACKGROUND: Well-being at work is an important aspect of a workforce strategy. The aim of the study was to explore and evaluate psychosocial factors and health and work-related outcomes of practices assistants depending on their employment status in general medical practices. METHODS: This observational study was based on a questionnaire survey to evaluate psychosocial aspects at work in general medical practices. A standardized questionnaire was used, the Copenhagen Psychosocial Questionnaire (COPSOQ). Beside descriptive analyses linear regression analyses were performed for each health and work-related outcome scale of the COPSOQ. RESULTS: 586 practice assistants out of 794 respondents (73.8 %) from 234 general medical practices completed the questionnaire. Practice assistants reported the highest scores for the psychosocial factor 'sense of community' (mean = 85.9) and the lower score for 'influence at work' (mean = 41.2). Moreover, practice assistants who worked part-time rated their psychosocial factors at work and health-related outcomes more positively than full-time employees. Furthermore, the two scales of health related outcomes 'burnout' and 'job satisfaction' showed strong associations between different psychosocial factors and socio-demographic variables. CONCLUSIONS: Psychosocial factors at work influence well-being at work and could be strong risk factors for poor health and work-related outcomes. Effective management of these issues could have an impact on the retention and recruitment of health care staff. PMID- 26560753 TI - Modulation of tumor immunity: a patent evaluation of WO2015026684A1. AB - A high percentage of regulatory T cells (Tregs) among tumor-infiltrating lymphocytes weakens the immune response against tumors. The anergy of effector T cells (Teff) can be reversed by immune checkpoint treatment, which inhibits Tregs and boosts the activation of Teff. Both effects can be obtained by triggering the glucocorticoid-induced TNF receptor-related (GITR), a costimulatory molecule expressed by Teff and Tregs, and by inhibiting the programmed cell death (PD)-1 receptor, an inhibitory molecule expressed by Teff. Patent W02015026684A1 provides a method of treating human tumors using a combination of a molecule triggering GITR and another inhibiting PD-1. The treatment approach was tested on three murine models of cancer, and the synergic effect of antihuman antibodies (Abs) in combination was tested in mixed lymphocyte reactions. Immune checkpoint treatment can break tolerance toward tumors and promote tumor rejection. The patented approach is very interesting and might be successful. The combined use of PD-1 antagonists and GITR agonists is synergic and tumor-centered, and adverse events might be less problematic than expected. A crucial point in translating the murine studies to humans is the differences between murine and human GITR and the evidence that some antihuman GITR Abs are not agonists. PMID- 26560754 TI - 5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children. AB - BACKGROUND: There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity -the intensity of an individual's response to other's emotions- has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G*E). Compared to children homozygous for the L-allele (LL genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. METHODS: Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children's self reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or "smile" muscle and the corrugator or "frown" muscle, n = 403). Parents reported on their negative and positive parenting behaviors. RESULTS: Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children's 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. CONCLUSIONS: We found no evidence for an association between the 5-HTTLPR polymorphism and children's emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G*E between the 5-HTTLPR and affective environmental stressors. PMID- 26560756 TI - PATHOLOGY AND MOLECULAR DETECTION OF RABIES VIRUS IN FERRET BADGERS ASSOCIATED WITH A RABIES OUTBREAK IN TAIWAN. AB - Until Rabies virus (RABV) infection in Taiwan ferret badgers (TWFB; Melogale moschata subaurantiaca) was diagnosed in mid-June 2013, Taiwan had been considered rabies free for >50 yr. Although rabies has also been reported in ferret badgers in China, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. We performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid TWFBs and evaluated archival paraffin-embedded tissue blocks of six other TWFBs necropsied during 2004 and 2012. As in other RABV-infected species, the characteristic pathologic changes in TWFBs were nonsuppurative meningoencephalomyelitis, ganglionitis, and the formation of typical intracytoplasmic Negri bodies, with the brain stem most affected. There was also variable spongiform degeneration, primarily in the perikaryon of neurons and neuropil, in the cerebral cortex, thalamus, and brain stem. In nonnervous system tissues, representative lesions included adrenal necrosis and lymphocytic interstitial sialadenitis. Immunohistochemical staining and fluorescent antibody test demonstrated viral antigens in the perikaryon of the neurons and axonal or dendritic processes throughout the nervous tissue and in the macrophages in various tissues. Similar to raccoons (Procyon lotor) and skunks (Mephitidae), the nervous tissue of rabid TWFBs displayed widely dispersed lesions, RABV antigens, and large numbers of Negri bodies. We traced the earliest rabid TWFB case back to 2004. PMID- 26560755 TI - Analysis of key genes of jasmonic acid mediated signal pathway for defense against insect damages by comparative transcriptome sequencing. AB - Corn defense systems against insect herbivory involve activation of genes that lead to metabolic reconfigurations to produce toxic compounds, proteinase inhibitors, oxidative enzymes, and behavior-modifying volatiles. Similar responses occur when the plant is exposed to methyl jasmonate (MeJA). To compare the defense responses between stalk borer feeding and exogenous MeJA on a transcriptional level, we employed deep transcriptome sequencing methods following Ostrinia furnacalis leaf feeding and MeJA leaf treatment. 39,636 genes were found to be differentially expressed with O. furnacalis feeding, MeJA application, and O. furnacalis feeding and MeJA application. Following Gene Ontology enrichment analysis of the up- or down- regulated genes, many were implicated in metabolic processes, stimuli-responsive catalytic activity, and transfer activity. Fifteen genes that indicated significant changes in the O. furnacalis feeding group: LOX1, ASN1, eIF3, DXS, AOS, TIM, LOX5, BBTI2, BBTI11, BBTI12, BBTI13, Cl-1B, TPS10, DOX, and A20/AN1 were found to almost all be involved in jasmonate defense signaling pathways. All of the data demonstrate that the jasmonate defense signal pathway is a major defense signaling pathways of Asian corn borer's defense against insect herbivory. The transcriptome data are publically available at NCBI SRA: SRS965087. PMID- 26560757 TI - Liquid chromatographic determination of caffeine and adrenergic stimulants in food supplements sold in Brazilian e-commerce for weight loss and physical fitness. AB - Methyl-xanthines and adrenergic stimulants, such as caffeine and synephrine, are commonly added to food supplements due to their stimulating and thermogenic effects. In addition, the abusive consumption of food supplements with ergogenic and aesthetic purposes has been observed worldwide. This work describes the study of caffeine, p-synephrine, hordenine, octopamine, tyramine, ephedrine and salicin as stimulants in dietary supplements marketed in Brazil for weight loss and physical fitness claims. A total of 94 different products were acquired from 30 Brazilian websites. Thus, the sampling of marketed supplements was performed in virtual commerce (e-commerce) with claims of weight loss, appetite reduction, fat burning and metabolism acceleration. The developed analytical method involved the separation of the stimulants by HPLC with diode array detection (HPLC-DAD) by using a gradient elution of flow rate (0.7-2.5 ml min(-1)) and mobile phase composition (0.1% H3PO4/methanol). The validated method was applied to the study of 46 dietary supplements. Caffeine, p-synephrine and ephedrine were found to be present as stimulants in 52% of the studied samples marketed as encapsulated or bulk forms. Caffeine was found to be present in concentrations that represent doses from 25.0 to 1476.7 mg day(-1). Synephrine was found in concentrations that represent doses from 59.1 to 127.0 mg day(-1). Ephedrine was found to be associated with caffeine in one formulation at a concentration representing a 26.1 mg day(-1) dosage. PMID- 26560758 TI - Changes in lean and skeletal muscle body mass in adult females with anorexia nervosa before and after weight restoration. AB - BACKGROUND & AIMS: Data on the deficits in lean body mass (LBM) and total body skeletal muscle mass (SM) in anorexia nervosa (AN) is scarce and inconsistent. Furthermore, the usefulness of the reported body mass index (BMI) severity cut off for AN has not been tested with respect to these important parameters. The study had two aims, namely to study LBM patterns and SM in adult females with AN before and after weight restoration, and to examine the clinical usefulness of the 16.5 kg/m2 BMI cut-off for assessing the protein status in terms of LBM and SM in AN patients. METHODS: Body composition was measured by dual-energy X-ray absorptiometry (DXA) before and after weight gain in 90 adult female inpatients with AN, and 90 controls matched by post-treatment BMI and age. Patients were stratified into two groups using BMI 16.5 kg/m2 as a cut-off. RESULTS: Before weight restoration, patients in the BMI<=16.5 kg/m2 subgroup (n = 65) had lower LBM, SM and lean extremity mass percentage, but higher %LBM and lean trunk-to extremity ratio on average than controls. However, those with BMI >16.5 kg/m2 (n = 25) displayed lower lean extremity mass percentage and higher %LBM, but no significant differences in LBM and SM with respect to controls. Moreover the time * subgroup interaction was significant in terms of LBM and SM, meaning that, changes occur in different manner over time in the two AN subgroups. However no differences were found between the two AN subgroups in either demographic or other eating disorder characteristics. After weight gain, normalization of LBM, %LBM, lean extremity mass percentage and SM was achieved across the entire AN sample, and the BMI<=16.5 kg/m2 subgroup. The fat mass was the major determinant of gain in LBM; the higher the FM at baseline, the greater the increase in LBM. CONCLUSIONS: Our results suggest a BMI cut-off <=16.5 kg/m2 as a clinical threshold for determining AN severity. As short-term weight restoration is associated with a normalization in LBM and SM, it appears that biological regulation of weight gain remains intact in AN, i.e., unaffected by the severity of malnutrition. CLINICAL TRIALS REGISTRY: Changes in lean and skeletal muscle body mass in adult females with anorexia nervosa before and after weight restoration (ISRCTN168721194). PMID- 26560760 TI - Massive parallel processing of image reconstruction from bispectrum through turbulence. AB - This paper presents a massively parallel method for the phase reconstruction of an object from its bispectrum phase. Our aim is to recover an enhanced version of a turbulence-corrupted image by developing an efficient and fast parallel image restoration algorithm. The proposed massively parallel bispectrum algorithm relies on multiple block parallelization. Further, in each block, we employ wavefront processing through strength reduction to parallelize an iterative algorithm. Results are presented and compared with the existing iterative bispectrum method. We report a speed-up factor of 85.94 with respect to sequential implementation of the same algorithm for an image size of 1024*1024. PMID- 26560761 TI - Compact noise-like pulse fiber laser and its application for supercontinuum generation in highly nonlinear fiber. AB - We report on supercontinuum generation in a highly nonlinear fiber (HNLF) pumped by noise-like pulses (NLPs) emitted from a compact fiber ring laser. The compact erbium-doped fiber ring laser is constructed by using an optical integrated component and mode-locked by the nonlinear polarization rotation technique. The laser produces NLPs with a 3-dB spectral bandwidth of 60.2 nm, repetition rate of 9.36 MHz, and pulse energy of 2.8 nJ. Numerical simulations reproduce the generation of NLPs in the experiment. The NLPs are then launched into a 110-m long HNLF and a supercontinuum with a 20-dB spectral width over 500 nm is obtained. Such a simple and inexpensive supercontinuum-generation system is a potential alternative for various practical applications. PMID- 26560759 TI - The association between green space and depressive symptoms in pregnant women: moderating roles of socioeconomic status and physical activity. AB - BACKGROUND: The current study explored the association between green space and depression in a deprived, multiethnic sample of pregnant women, and examined moderating and mediating variables. METHOD: 7547 women recruited to the 'Born in Bradford' cohort completed a questionnaire during pregnancy. A binary measure of depressive symptoms was calculated using a validated survey. Two green space measures were used: quintiles of residential greenness calculated using the normalised difference vegetation index for three neighbourhood sizes (100, 300 and 500 m buffer zones around participant addresses); access to major green spaces estimated as straight line distance between participant address and nearest green space (>0.5 hectares). Logistic regression analyses examined relationships between green space and depressive symptoms, controlling for ethnicity, demographics, socioeconomic status (SES) and health behaviours. Multiplicative interactions explored variations by ethnic group, SES or activity levels. Mediation analysis assessed indirect effects via physical activity. RESULTS: Pregnant women in the greener quintiles were 18-23% less likely to report depressive symptoms than those in the least green quintile (for within 100 m of green space buffer zone). The green space-depressive symptoms association was significant for women with lower education or who were active. Physical activity partially mediated the association of green space, but explained only a small portion of the direct effect. CONCLUSIONS: Higher residential greenness was associated with a reduced likelihood of depressive symptoms. Associations may be stronger for more disadvantaged groups and for those who are already physically active. Improving green space is a promising intervention to reduce risk of depression in disadvantaged groups. PMID- 26560762 TI - High brightness laser-diode device emitting 160 watts from a 100 MUm/NA 0.22 fiber. AB - A practical method of achieving a high-brightness and high-power fiber-coupled laser-diode device is demonstrated both by experiment and ZEMAX software simulation, which is obtained by a beam transformation system, free-space beam combining, and polarization beam combining based on a mini-bar laser-diode chip. Using this method, fiber-coupled laser-diode module output power from the multimode fiber with 100 MUm core diameter and 0.22 numerical aperture (NA) could reach 174 W, with equalizing brightness of 14.2 MW/(cm2.sr). By this method, much wider applications of fiber-coupled laser-diodes are anticipated. PMID- 26560763 TI - Fringe order error in multifrequency fringe projection phase unwrapping: reason and correction. AB - A multifrequency fringe projection phase unwrapping algorithm (MFPPUA) is important to fringe projection profilometry, especially when a discontinuous object is measured. However, a fringe order error (FOE) may occur when MFPPUA is adopted. An FOE will result in error to the unwrapped phase. Although this kind of phase error does not spread, it brings error to the eventual 3D measurement results. Therefore, an FOE or its adverse influence should be obviated. In this paper, reasons for the occurrence of an FOE are theoretically analyzed and experimentally explored. Methods to correct the phase error caused by an FOE are proposed. Experimental results demonstrate that the proposed methods are valid in eliminating the adverse influence of an FOE. PMID- 26560764 TI - Thin-disk laser pump schemes for large number of passes and moderate pump source quality. AB - Thin-disk laser pump layouts yielding an increased number of passes for a given pump module size and pump source quality are proposed. These layouts result from a general scheme based on merging two simpler pump optics arrangements. Some peculiar examples can be realized by adapting standard, commercially available pump optics with an additional mirror pair. More pump passes yield better efficiency, opening the way for the usage of active materials with low absorption. In a standard multipass pump design, scaling of the number of beam passes brings about an increase in the overall size of the optical arrangement or an increase in the pump source quality requirements. Such increases are minimized in our scheme, making them eligible for industrial applications. PMID- 26560765 TI - Empirical mode decomposition profilometry: small-scale capabilities and comparison to Fourier transform profilometry. AB - We present the empirical mode decomposition profilometry (EMDP) for the analysis of fringe projection profilometry (FPP) images. It is based on an iterative filter, using empirical mode decomposition, which is free of spatial filtering and adapted for surfaces characterized by a broadband spectrum of deformation. Its performances are compared to Fourier transform profilometry, the benchmark of FPP. We show both numerically and experimentally that using EMDP improves strongly the profilometry small-scale capabilities. Moreover, the height reconstruction distortion is much lower: the reconstructed height field is now both spectrally and statistically accurate. EMDP is thus particularly suited to quantitative experiments. PMID- 26560766 TI - Photonic crystal fiber modal interferometer based on thin-core-fiber mode exciter. AB - A thin-core-fiber excited photonic crystal fiber modal interferometer has been proposed and experimentally demonstrated. By employing a thin-core fiber as the mode exciter, both of the core and cladding modes propagate in the photonic crystal fiber and interfere with each other. The experimental results show that the transmission dips corresponding to different-order modes have various strain responses with opposite shift directions. The strain sensitivity could be improved to 58.57 pm/MUepsilon for the applied strain from 0 to 491 MUepsilon by utilizing the wavelength interval between the dips with opposite shift directions. Moreover, due to the pure silica property of the employed photonic crystal fiber, the proposed fiber modal interferometer exhibits a low-temperature sensitivity of about 0.56 pm/ degrees C within a temperature range from 26.4 degrees C (room temperature) to 70 degrees C. Additionally, the proposed fiber modal interferometer has several advantages, such as good stability, compact structure, and simple fabrication. Therefore, it is more applicable for strain measurement with reducing temperature cross-sensitivity. PMID- 26560767 TI - 2 kW narrow spectral width monolithic continuous wave in a near-diffraction limited fiber laser. AB - We demonstrate a monolithic continuous wave (CW) fiber laser source at 1070 nm, producing 2 kW laser power with a very narrow spectral width (~75 GHz) and near diffraction-limited beam quality (M2<1.4). The laser consists of a CW fiber laser oscillator and two double cladding fiber amplifiers in the master oscillator power amplifier configuration. The master oscillator is a distributed Bragg reflected fiber laser, producing ~6 W laser power with ~25 GHz spectral width. The two double cladding fiber amplifiers were developed to enhance the laser power up to ~200 and ~2050 W, respectively. The slope efficiency of the main amplifier reaches 84.8%. Under the full power output, the 3 dB spectral width and 20 dB spectral width of the laser emission spectrum was ~75 GHz and 1.2 nm, respectively. PMID- 26560768 TI - Analysis and characterization of high-resolution and high-aspect-ratio imaging fiber bundles. AB - High-contrast imaging fiber bundles (FBs) are characterized and modeled for wide angle and high-resolution imaging applications. Scanning electron microscope images of FB cross sections are taken to measure physical parameters and verify the variations of irregular fibers due to the fabrication process. Modal analysis tools are developed that include irregularities in the fiber core shapes and provide results in agreement with experimental measurements. The modeling demonstrates that the irregular fibers significantly outperform a perfectly regular "ideal" array. Using this method, FBs are designed that can provide high contrast with core pitches of only a few wavelengths of the guided light. Structural modifications of the commercially available FB can reduce the core pitch by 60% for higher resolution image relay. PMID- 26560769 TI - Filterless frequency 12-tupling optical millimeter-wave generation using two cascaded dual-parallel Mach-Zehnder modulators. AB - A novel frequency 12-tupling optical millimeter-wave (mm-wave) generation using two cascaded dual-parallel Mach-Zehnder modulators (DP-MZMs) without an optical filter is proposed and demonstrated by computer simulation. By properly adjusting the amplitude and phase of radio frequency (RF) driving signal and the direct current (DC) bias points of two DP-MZMs, a 120 GHz mm-wave with an optical sideband suppression ratio (OSSR) of 25.1 dB and a radio frequency spurious suppression ratio (RFSSR) of 19.1 dB is shown to be generated from a 10 GHz RF driving signal, which largely reduces the response frequency of electronic devices. Furthermore, it is also proved to be valid that even if the phase difference of RF driving signals, the RF driving voltage, and the DC bias voltage deviate from the ideal values to a certain degree, the performance is still acceptable. Since no optical filter is employed to suppress the undesired optical sidebands, a high-spectral-purity mm-wave signal tunable from 48 to 216 GHz can be obtained theoretically when a RF driving signal from 4 to 18 GHz is applied to the DP-MZMs, and the system can be readily implemented in wavelength-division multiplexing upconversion systems to provide high-quality optical local oscillator signal. PMID- 26560770 TI - Interband cascade lasers with long lifetimes. AB - Narrow-ridge interband cascade lasers were subjected to accelerated aging. The aging curves were statistically evaluated by a log-normal distribution of the failure time, and by the mixed effects of the degradation parameters. Based on 10,000 h of output power trend data for lasers operating at 90 degrees C and the maximum cw power, an unexpectedly long lifetime is predicted. The projected lifetimes range from about 500,000 h (57 years) for the linear degradation model to 183,000 h (21 years) for the exponential one. PMID- 26560771 TI - Frequency stability of a wavelength meter and applications to laser frequency stabilization. AB - Interferometric wavelength meters have attained frequency resolutions down to the megahertz range. In particular, Fizeau interferometers, which have no moving parts, are becoming a popular tool for laser characterization and stabilization. In this paper, we characterize such a wavelength meter using an ultrastable laser in terms of relative frequency instability sigma(y)(tau) and demonstrate that it can achieve a short-term instability sigma(y)(1s)~2*10(-10) and a frequency drift of order 10 MHz/day. We use this apparatus to demonstrate frequency control of a near-infrared laser, where a frequency instability below 3*10(-10) from 1 to 2000 s is achieved. Such performance is, for example, adequate for ion trapping and atom cooling experiments. PMID- 26560772 TI - Improving the spectral resolution of flat-field concave grating miniature spectrometers by dividing a wide spectral band into two narrow ones. AB - In this study, a new flat-field concave grating miniature spectrometer is proposed with improved resolution across a wide spectral band. A mirror is added to a conventional concave grating spectrometer and placed near the existing detector array, allowing a wide spectral band to be divided into two adjacent subspectral bands. One of these bands is directly detected by the detector, and the other is indirectly analyzed by the same detector after being reflected by the mirror. These two subspectral bands share the same entrance slit, concave grating, and detector, which allows for a compact size, while maintaining an improved spectral resolution across the entire spectral band. The positions of the mirror and other parameters of the spectrometer are designed by a computer procedure and the optical design software ZEMAX. Simulation results show that the resolution of this kind of flat-field concave grating miniature spectrometer is better than 1.6 nm across a spectral band of 700 nm. Experiments based on three laser sources reveal that the measured resolutions are comparable to the simulated ones, with a maximum relative error between them of less than 19%. PMID- 26560773 TI - Tellurite glass defect-core spiral photonic crystal fiber with low loss and large negative flattened dispersion over S + C + L + U wavelength bands. AB - A defected-core spiral photonic crystal fiber is proposed to achieve very large negative flattened dispersion and small confinement loss. Simulation results reveal that the designed structure exhibits very large flattened dispersion over S+C+L+U wavelength bands and an average dispersion of about -720.7 ps nm(-1) km( 1) with an absolute dispersion variation of 12.7 ps nm(-1) km(-1) over the wavelength ranging from 1.45 to 1.65 MUm. The proposed fiber has five air-hole rings in the cladding leading to very small confinement loss of 0.00111 dB/km at the excitation wavelength of 1.55 MUm. The tolerance of the fiber dispersion of +/-2% changing in the structural parameters is investigated for practical conditions. PMID- 26560775 TI - Retrieving mesopause temperature and line-of-sight wind from full-diurnal-cycle Na lidar observations. AB - Narrowband Na lidar measurement of mesopause region temperatures were pioneered by Fricke and von Zahn in 1985, in 1990 by She et al. at Colorado State University (CSU), with upgrades to measure both temperature and wind in 1994, and under sunlit conditions in 1996 with 24 h continuous observational capability in 2002. This paper details the assumptions and procedures for the retrieval of mesopause region temperatures, line-of-sight winds, and sodium densities from day and night signals from the CSU narrowband Na lidar. The Hanle effect and the effect of the pulsed laser line shape function on the accuracy of temperature and LOS wind retrieval are also discussed. PMID- 26560774 TI - Diffraction-limited step-zoom telescope by image restoration. AB - The design of a step-zoom telescope and its ability to achieve a diffraction limited performance is explored. The basic idea is to include digital postprocessing to compensate for changes in the modulation transfer function of the system, assuming the knowledge of the range to the object. The instrument is conformed of a two-mirror telescope, two lenses, and a detector. High-quality images and a zoom telescope that ranges from 22 to 61 f-number is achieved by moving the primary mirror and two lenses. The preliminary calculations for the design process and a simulation that shows the performance of the step-zoom telescope are described. PMID- 26560776 TI - Spectral density response functions for modulated polarimeters. AB - Conventional imaging devices are often compared using their optical transfer functions (OTFs) in space and their impulse responses in time. Modulated polarimeters cannot be directly compared this way, since they are frequency multiplexed. Here we define a spectral density response function that describes how the spectral density matrix of the Stokes parameters for an object transfers through a modulated polarimeter. This response function facilitates the objective comparison of polarimeters in a way that is analogous to the OTF for conventional imaging systems. The spectral density response is used to calculate a Wiener filter for a rotating analyzer polarimeter as an example of filter optimization for modulated polarimetry. PMID- 26560777 TI - Diode-end-pumped single-longitudinal-mode Er:LuAG laser with intracavity etalons at 1.6 MUm. AB - We present a laser-diode-pumped 1.6 MUm single-longitudinal-mode Er:LuAG laser. The intracavity etalons were used as mode selectors for the single-longitudinal mode operation. The maximum single-longitudinal-mode output power was 153 mW with the wavelength of 1650.2 nm at the pump power of 9.18 W, corresponding to a slope efficiency of 4.3%. The M2 factor was measured to be 1.07. In addition, by changing the thickness of the etalons, a maximum single-longitudinal-mode output power of 114 mW at 1628.1 nm with a slope efficiency of 3.5% was also achieved. To our knowledge, the intracavity etalons Er:LuAG laser operated at single longitudinal-mode is being reported for the first time. PMID- 26560778 TI - Binocular open-view system to perform estimations of aberrations and scattering in the human eye. AB - We present a system that integrates a double-pass (DP) instrument and a Hartmann Shack (HS) wavefront sensor to provide information not only on aberrations, but also on the scattering that occurs in the human eye. A binocular open-view design permits evaluations to be made under normal viewing conditions. Furthermore, the system is able to compensate for both the spherical and astigmatic refractive errors that occur during measurements by using devices with configurable optical power. The DP and HS techniques provide comparable data after estimating wavefront slopes with respect to the intersections of an ideal grid and compensating for residual errors caused by the optical defects of the measuring system. Once comparable data is obtained, it is possible to use this combined manner of assessment to provide information on scattering. Measurements in an artificial eye suggest that the characteristics of the ocular fundus may induce deviations of DP with respect to the HS data. These differences were quantified in terms of the modulation transfer function in young, healthy eyes measured in infrared light to demonstrate the potential use of the system in visual optics studies. PMID- 26560779 TI - Diode-pumped tri-wavelength synchronously mode-locked Yb,Y:CaF2 laser. AB - A tri-wavelength synchronous mode-locking operation of a diode-pumped Yb,Y:CaF2 laser has been investigated by using a semiconductor saturable absorber mirror at 1 MUm. The tri-wavelength synchronous mode-locking pulses were centered at 1045.7, 1047.6, and 1049.5 nm. An interference pattern was obtained in the autocorrelation trace, where the beat pulse width was 3.2 ps and the repetition rate was 0.52 THz. The maximum average output power was 196 mW with pulse width 120 ps and repetition rate of 89 MHz. PMID- 26560780 TI - Parallel-quadrature on-axis phase-shifting common-path interferometer using a polarizing beam splitter. AB - A common-path parallel-quadrature on-axis phase-shifting interferometry using a modified Michelson configuration with a polarizing cube beam splitter is proposed for quantitative phase measurement. The frequency spectrum of the circularly polarized object beam is split into two beams using a beam splitter. One beam is converted to a 45 degrees linearly polarized beam to act as the object beam, and the other beam is low-filtered by a pinhole mirror to act as the reference beam. Two interferograms with quadrature phase shift can be simultaneously captured by combining the 45 degrees linearly polarized object beam with the circularly polarized reference beam through a 45 degrees tilted polarizing cube beam splitter, and the phase of a specimen can be then retrieved through a two-step phase-shifting algorithm. Experiments are carried out to demonstrate the validity and stability of the proposed method. PMID- 26560781 TI - Developing a video tracking method to study interactions between close pairs of optically trapped particles in three dimensions. AB - We develop a video tracking method that utilizes an interpolation-based normalized cross-correlation approach to track the position of microscopic spherical particles in three dimensions. Subnanometer resolution is demonstrated. The method does not assume that the particle's image is radially symmetric, making it useful for determining the position when particles are close and their images overlap. This is demonstrated in a study of the electrostatic and hydrodynamic interactions between a pair of beads in dual laser tweezers traps. PMID- 26560782 TI - Tolerance analysis of multilayer diffractive optics based on polychromatic integral diffraction efficiency. AB - Multilayer diffractive optical elements (MLDOEs) can achieve high diffraction efficiency for broadband wavelength. Polychromatic integral diffraction efficiency (PIDE) is the key concern for evaluating diffraction efficiency over the waveband. The modulation transfer function of a hybrid refractive-diffractive optical system is directly affected by the PIDE. The relationship between PIDE and continuous manufacturing errors for microstructure heights and periodic widths of MLDOEs is studied theoretically in this paper, and an example of MLDOEs is discussed in the visible waveband. The analysis results can be used for manufacturing error control in microstructure heights and periodic widths. PMID- 26560783 TI - Quantitative analysis of essential oils of Thymus daenensis using laser-induced fluorescence and Raman spectroscopy. AB - Laser-induced fluorescence and Raman spectroscopy are used for the investigation of different genotypes of Thymus daenensis native to the Ilam province of Iran. Different genotypes of T. daenensis essential oils, labeled T1 through T7, possess slight differences with regard to the composition of the thymol. The gas chromatography-mass spectrometry (GC-MS) method is performed to determine the concentration of each constituent as a reference method. The Raman spectra of different concentrations of pure thymol dissolved in hexane as standard samples are obtained via a laboratory prototype Raman spectroscopy setup for the calculation of the calibration curve. The regression coefficient and limit of detection are calculated. The possibility of the differentiation of different genotypes of T. daenensis is also examined by laser-induced fluorescence spectroscopy, although we do not know the exact amounts of their components. All the fluorescence spectral information is used jointly by cluster analysis to differentiate between 7 genotypes. Our results demonstrate the acceptable precision of Raman spectroscopy with GC-MS and corroborate the capacity of Raman spectroscopy in applications in the quantitative analysis field. Furthermore, the cluster analysis results show that laser-induced fluorescence spectroscopy is an acceptable technique for the rapid classification of different genotypes of T. daenensis without having any previous information of their exact amount of constituents. So, the ability to rapidly and nondestructively differentiate between genotypes makes it possible to efficiently select high-quality herbs from many samples. PMID- 26560784 TI - High numerical aperture holographic microscopy reconstruction with extended z range. AB - A holographic microscopy reconstruction method compatible with a high numerical aperture microscope objective (MO) up to NA=1.4 is proposed. After off-axis and reference field curvature corrections, and after selection of the +1 grating order holographic image, a phase mask that transforms the optical elements of the holographic setup into an afocal device is applied in the camera plane. The reconstruction is then made by the angular spectrum method. The field is first propagated in the image half-space from the camera to the afocal image of the MO optimal plane (the plane for which the MO has been designed) by using a quadratic kernel. The field is then propagated from the MO optimal plane to the object with the exact kernel. Calibration of the reconstruction is made by imaging a calibrated object such as a USAF resolution target for different positions along z. Once the calibration is done, the reconstruction can be made with an object located in any plane z. The reconstruction method has been validated experimentally with a USAF target imaged with a NA=1.4 microscope objective. Near optimal resolution is obtained over an extended range (+/-50 MUm) of z locations. PMID- 26560785 TI - Silver/cyclic olefin copolymer hollow glass waveguides for infrared laser delivery. AB - Metal/dielectric-coated hollow glass waveguides (HGWs) have been studied extensively for the efficient transmission of radiation over a broad spectral range. In this study, a low-absorption optical polymer, cyclic olefin copolymer (COC), is investigated as a dielectric material for HGWs designed for the delivery of various IR lasers. Using established silver (Ag) plating techniques and a newly optimized polymer-coating procedure, Ag/COC HGWs with low attenuation coefficients are fabricated for operation at the following three wavelengths: 808 nm, 1.064 MUm, and 2.94 MUm. The spectral responses of the HGW designs are used to develop a film thickness dependency of the COC layer formation based on the concentration of the solution used in the polymer deposition procedure. Further, the attenuation coefficients of the HGWs are measured using the cutback method at the three wavelengths as a function of the curvature of the waveguide. In order of increasing operation, the attenuation coefficients are measured to be 0.549, 0.095, and 0.298 dB/m for the HGWs in the straight configuration. These experimental values for the straight attenuation coefficients are compared to theoretical values calculated using a ray transfer matrix approach and are found to be in good agreement. PMID- 26560786 TI - Alignment analyses of a galvanometer-based scanner in free-space Fourier domain optical coherence tomography. AB - Free-space Fourier domain optical coherence tomography is adopted for biomedical imaging with ultrahigh resolution, in which the setup consists of an interferometer and a spectrometer. Two-dimensional lateral sampling in the sample arm of the interferometer is achieved by using a galvanometer-based scanner. Optical path difference (OPD) drift in the full scan field of view is observed in the assembly process of the scanner. A galvo mirror mount offset with respect to the rotation axis is demonstrated as the derivation of this OPD drift by both geometric analyses and model building. Then, an iterative assembly process of the scanner is proposed with the OPD drift taken as the alignment criteria. PMID- 26560787 TI - Polarization dependence of the nonlinear interaction between sinusoidally modulated optical signals in a randomly birefringent optical fiber. AB - In this paper, polarization dependence of the nonlinear interaction between two sinusoidally modulated optical signals (SMOSs) in a randomly birefringent silica optical fiber is investigated analytically and experimentally. Vector analysis is performed on the nonlinear interaction between two orthogonally polarized or co polarized SMOSs carried by identical or different laser wavelengths in a randomly birefringent silica optical fiber. Dependence of the nonlinear interaction on the polarization states of two SMOSs is investigated by analyzing the power of the first-order sideband as a result of the nonlinear interaction. The presented theoretical study reveals the polarization dependence of the nonlinear interaction between two SMOSs as confirmed by the close agreement between theoretical and experimental results. This study provides insight into the polarization dependence of operation of a Kerr phase interrogator and the tools for optimizing the performance of sensing devices based on a Kerr phase interrogator. PMID- 26560788 TI - Theoretical analysis on the rotation-induced frequency difference in ring lasers with coupled cavities. AB - We analyzed the effective scale factor of ring laser gyros with coupled cavities in a general way. The coupled cavities can be made of both an odd and even number of mirrors, or even fiber coil. Compared with the "zero-vector-area" design in previous publications, we use the propagation loss rather than transmittance and reflectivity of mirrors to characterize the coupled cavities, which are more universal and controllable. In addition, we found the area of the coupled cavities could further enhance the effective scale factor by 1+l/L, where l and L are the round-trip length of the ring lasers and the coupled cavity, respectively. Therefore, the scheme using coupled cavities to enhance the sensitivity is more practical. These findings are important to realize highly sensitive ring laser gyros. PMID- 26560789 TI - 3D mouse shape reconstruction based on phase-shifting algorithm for fluorescence molecular tomography imaging system. AB - This work introduces a fast, low-cost, robust method based on fringe pattern and phase shifting to obtain three-dimensional (3D) mouse surface geometry for fluorescence molecular tomography (FMT) imaging. We used two pico projector/webcam pairs to project and capture fringe patterns from different views. We first calibrated the pico projectors and the webcams to obtain their system parameters. Each pico projector/webcam pair had its own coordinate system. We used a cylindrical calibration bar to calculate the transformation matrix between these two coordinate systems. After that, the pico projectors projected nine fringe patterns with a phase-shifting step of 2pi/9 onto the surface of a mouse-shaped phantom. The deformed fringe patterns were captured by the corresponding webcam respectively, and then were used to construct two phase maps, which were further converted to two 3D surfaces composed of scattered points. The two 3D point clouds were further merged into one with the transformation matrix. The surface extraction process took less than 30 seconds. Finally, we applied the Digiwarp method to warp a standard Digimouse into the measured surface. The proposed method can reconstruct the surface of a mouse sized object with an accuracy of 0.5 mm, which we believe is sufficient to obtain a finite element mesh for FMT imaging. We performed an FMT experiment using a mouse-shaped phantom with one embedded fluorescence capillary target. With the warped finite element mesh, we successfully reconstructed the target, which validated our surface extraction approach. PMID- 26560790 TI - Analysis of a segmented q-plate tunable retarder for the generation of first order vector beams. AB - In this work we study a prototype q-plate segmented tunable liquid crystal retarder device. It shows a large modulation range (5pi rad for a wavelength of 633 nm and near 2pi for 1550 nm) and a large clear aperture of one inch diameter. We analyze the operation of the q-plate in terms of Jones matrices and provide different matrix decompositions useful for its analysis, including the polarization transformations, the effect of the tunable phase shift, and the effect of quantization levels (the device is segmented in 12 angular sectors). We also show a very simple and robust optical system capable of generating all polarization states on the first-order Poincare sphere. An optical polarization rotator and a linear retarder are used in a geometry that allows the generation of all states in the zero-order Poincare sphere simply by tuning two retardance parameters. We then use this system with the q-plate device to directly map an input arbitrary state of polarization to a corresponding first-order vectorial beam. This optical system would be more practical for high speed and programmable generation of vector beams than other systems reported so far. Experimental results are presented. PMID- 26560791 TI - Detection and correction of wavefront errors caused by slight reference tilt in two-step phase-shifting digital holography. AB - A simple and convenient method, without the need for any additional optical devices and measurements, is suggested to improve the quality of the reconstructed object wavefront in two-step phase-shifting digital holography by decreasing the errors caused by reference beam tilt, which often occurs in practice and subsequently introduces phase distortion in the reconstructed wave. The effects of reference beam tilt in two-step generalized interferometry is analyzed theoretically, showing that this tilt incurs no error either on the extracted phase shift or on the retrieved real object wave amplitude on the recording plane, but causes great deformation of the recovered object wavefront. A corresponding error detection and correction approach is proposed, and the formulas to calculate the tilt angle and correct the wavefront are deduced. A series of computer simulations to find and remove the wavefront errors caused by reference beam tilt demonstrate the effectiveness of this method. PMID- 26560792 TI - Wink-controlled polarization-switched telescopic contact lenses. AB - We describe a wink-controlled hands-free switching system for eye-borne telescopic vision, based on a previously tested fixed-magnification telescope embedded within scleral contact lenses. Here we integrate orthogonal polarizers into the contact lens covering the F/9.1 refractive 1* and F/9.6 catadioptric 2.8* vision paths, to allow switching via external liquid crystal shutters. We provide hands-free control by an infrared wink/blink monitor, using passive retroreflectors embedded within the contact lenses. We demonstrate system operation of the self-contained switching eyewear and the modified contact lenses with a life-size human eye model with mechanical "eyelids." PMID- 26560793 TI - Continuous zoom antenna for mobile visible light communication. AB - In this paper, we design a continuous zoom antenna for mobile visible light communication (VLC). In the design, a right-angle reflecting prism was adopted to fold the space optical path, thus decreasing the antenna thickness. The surface of each lens in the antenna is spherical, and the system cost is relatively low. Simulation results indicated that the designed system achieved the following performance: zoom ratio of 2.44, field of view (FOV) range of 18 degrees -48 degrees , system gain of 16.8, and system size of 18 mm*6 mm. Finally, we established an indoor VLC system model in a room the size of 5 m *5 m *3 m and compared the detection results of the zoom antenna and fixed-focus antenna obtained in a multisource communication environment, a mobile VLC environment, and a multiple-input multiple-output communication environment. The simulation results indicated that the continuous zoom antenna could realize large FOV and high gain. Moreover, the system showed improved stability, mobility, and environmental applicability. PMID- 26560794 TI - Generation of 1.5 W average power, 18 kHz repetition rate coherent mid ultraviolet radiation at 271.2 nm. AB - This paper presents to our knowledge a first time study on the generation of 1.5 W average power, 18 kHz repetition rate coherent mid-ultraviolet (UV) radiation at 271.2 nm. The work is based on frequency summing of coherent green (G: 510.6 nm) and yellow (Y: 578.2 nm) radiations of a copper-HBr laser in a beta-barium borate crystal. Average and peak sum frequency conversion efficiencies of about 13% and 16%, respectively, are obtained. The sum frequency results are experimentally analyzed in terms of the extent of matching of green and yellow pump radiations in space, time, and frequency domains. The result is of high significance for many applications in photonics components fabrication, semiconductor technology, and spectroscopy. PMID- 26560795 TI - Adaptive defect and pattern detection in amplitude and phase structures via photorefractive four-wave mixing. AB - This work comprises the theoretical and numerical validations of experimental work on pattern and defect detection of periodic amplitude and phase structures using four-wave mixing in photorefractive materials. The four-wave mixing optical processor uses intensity filtering in the Fourier domain. Specifically, the nonlinear transfer function describing four-wave mixing is modeled, and the theory for detection of amplitude and phase defects and dislocations are developed. Furthermore, numerical simulations are performed for these cases. The results show that this technique successfully detects the slightest defects clearly even with no prior enhancement. This technique should prove to be useful in quality control systems, production-line defect inspection, and e-beam lithography. PMID- 26560796 TI - Simulation and experimental study of aspect ratio limitation in Fresnel zone plates for hard-x-ray optics. AB - For acquiring high-contrast and high-brightness images in hard-x-ray optics, Fresnel zone plates with high aspect ratios (zone height/zone width) have been constantly pursued. However, knowledge of aspect ratio limits remains limited. This work explores the achievable aspect ratio limit in polymethyl methacrylate (PMMA) by electron-beam lithography (EBL) under 100 keV, and investigates the lithographic factors for this limitation. Both Monte Carlo simulation and EBL on thick PMMA are applied to investigate the profile evolution with exposure doses over 100 nm wide dense zones. A high-resolution scanning electron microscope at low acceleration mode for charging free is applied to characterize the resultant zone profiles. It was discovered for what we believe is the first time that the primary electron-beam spreading in PMMA and the proximity effect due to extra exposure from neighboring areas could be the major causes of limiting the aspect ratio. Using the optimized lithography condition, a 100 nm zone plate with aspect ratio of 15/1 was fabricated and its focusing property was characterized at the Shanghai Synchrotron Radiation Facility. The aspect ratio limit found in this work should be extremely useful for guiding further technical development in nanofabrication of high-quality Fresnel zone plates. PMID- 26560797 TI - Development of a design tool for closed-loop digital vibrometer. AB - The closed-loop technique has been demonstrated as a possible configuration to design a vibrometer based upon self-mixing interferometry. The electronic feedback loop allows a better linearity while extending the linearity range of a self-mixing interferometer. A deep analysis of the feedback loop is carried out in order to improve stability and performance through a digital approach. This work describes first the simulation of the closed-loop vibrometer, and then the performance obtained through its implementation on an FPGA based prototype. PMID- 26560798 TI - Effect of Molecular Architecture of PDMAEMA-POEGMA Random and Block Copolymers on Their Adsorption on Regenerated and Anionic Nanocelluloses and Evidence of Interfacial Water Expulsion. AB - Block copolymers of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) with varying block sizes were synthesized by consecutive reversible addition-fragmentation chain transfer (RAFT) polymerization and then exposed to cellulose substrates with different anionic charge density. The extent and dynamics of quaternized PDMAEMA-b-POEGMA adsorption on regenerated cellulose, cellulose nanofibrils (CNF), and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNF) was determined by using electromechanical and optical techniques, namely, quartz crystal microbalance (QCM-D) and surface plasmon resonance (SPR), respectively. PDMAEMA-b-POEGMA equilibrium adsorption increased with the anionic charge of cellulose, an indication of electrostatic interactions. Such an observation was further confirmed by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Depending on their architecture, adsorption on TOCNF of some of the PDMAEMA-b-POEGMA copolymers produced a significant reduction in QCM frequency, as expected from large mass uptake, while surprisingly, other copolymers induced the opposite effect. This latter, remarkable behavior was ascribed to coupled water expulsion from the interface upon charge neutralization of anionic surface sites with adsorbing cationic polymer segments. These observations were further investigated with SPR and QCM-D measurements using deuterium oxide solvent exchange to determine the amount of coupled water at the TOCNF-block copolymer interface. Finally, random copolymers with similar composition adsorbed to a larger extent compared to the respective block copolymers, revealing the effect of adsorbed loops and tails as well as hydration. PMID- 26560799 TI - Mercury-mediated cross-resistance to tellurite in Pseudomonas spp. isolated from the Chilean Antarctic territory. AB - Mercury salts and tellurite are among the most toxic compounds for microorganisms on Earth. Bacterial mercury resistance is established mainly via mercury reduction by the mer operon system. However, specific mechanisms underlying tellurite resistance are unknown to date. To identify new mechanisms for tellurite detoxification we demonstrate that mercury resistance mechanisms can trigger cross-protection against tellurite to a group of Pseudomonads isolated from the Chilean Antarctic territory. Sequencing of 16S rRNA of four isolated strains resulted in the identification of three Pseudomonads (ATH-5, ATH-41 and ATH-43) and a Psychrobacter (ATH-62) bacteria species. Phylogenetic analysis showed that ATH strains were related to other species previously isolated from cold aquatic and soil environments. Furthermore, the identified merA genes were related to merA sequences belonging to transposons commonly found in isolated bacteria from mercury contaminated sites. Pseudomonas ATH isolates exhibited increased tellurite resistance only in the presence of mercury, especially ATH 43. Determination of the growth curves, minimal inhibitory concentrations and growth inhibition zones showed different tellurite cross-resistance of the ATH strains and suggested a correlation with the presence of a mer operon. On the other hand, reactive oxygen species levels decreased while the thiol content increased when the isolates were grown in the presence of both toxicants. Finally, qPCR determinations of merA, merC and rpoS transcripts from ATH-43 showed a synergic expression pattern upon combined tellurite and mercury treatments. Altogether, the results suggest that mercury could trigger a cell response that confers mercury and tellurite resistance, and that the underlying mechanism participates in protection against oxidative damage. PMID- 26560800 TI - Accuracy of Aortic Annulus Diameter Measurement: Comparison of Multi-Detector CT, Two- and Three-Dimensional Echocardiography. AB - OBJECTIVE: Accurate preprocedural quantification of the aortic annulus diameter is crucial for the operative success of the aortic valve surgery and especially transcatheter aortic valve replacement (TAVR). We conducted a prospective study to compare the accuracy of preoperative aortic annulus measurements using different imaging methods and direct measurements for aortic valve surgery. METHODS: We enrolled 52 patients who underwent open aortic valve surgery between March 2012 and March 2014. Aortic annulus diameter was prospectively measured by transthoracic two-dimensional echocardiography (2D-TTE), transesophageal three dimensional echocardiography (3D-TEE), and multi-detector computed tomography (MDCT). Imaging measurements were performed blindly by lab technicians. At surgery, the aortic annulus diameter was directly measured. RESULTS: Of the three methods, MDCT provided the smallest error in determining aortic annulus size as compared with the measurements at surgery. The limit of agreement of the aortic diameter by MDCT was smallest in the present study. CONCLUSIONS: The MDCT provided the most accurate measurement of aortic annulus diameter compared with 2D-TTE and 3D-TEE. PMID- 26560801 TI - Illness perceptions are the main predictors of depression and anxiety symptoms in patients with chronic pain. AB - Depression and anxiety symptoms in chronic pain are associated with adverse clinical outcomes, and appear highly related to patient's illness perceptions as well as with marital adjustment. This study aimed to investigate the predictive value of pain variables, marital adjustment and illness perceptions on depression and anxiety in patients with chronic pain. Two hundred patients were recruited from a pain unit in a public hospital in the north of Portugal. Patients completed a questionnaire that assessed illness perceptions (IPQ-Brief), marital adjustment (revised dyadic adjustment scale), depression and anxiety symptoms (hospital anxiety depression scale) and pain variables (pain intensity and pain disability index). Depression and anxiety symptoms were associated with pain intensity, pain-related disability, marital adjustment and illness perceptions. Results from hierarchical regression showed that illness perceptions contributed significantly to depression and anxiety symptoms over and above the effects of pain intensity, pain-related disability and marital adjustment, after controlling for gender. In multivariate analyses, pain intensity, pain-related disability and marital adjustment were uniquely related to depression and anxiety symptoms, whereas specific illness perceptions were uniquely related to depression symptoms (identity, treatment control, emotional response and coherence) and to anxiety symptoms (identity, emotional response and concern). Perceptions of greater symptomatology (identity) and of emotional impact, and lesser perceptions of treatment control and understanding of chronic pain (illness comprehensibility) were significantly associated with increased depression symptoms. Perceptions of greater symptomatology (identity), emotional impact and greater concern were associated with anxiety symptoms. These findings indicate that the contribution of illness perceptions was greater than that made by traditional covariates, and may therefore be a useful basis for future psychological interventions. PMID- 26560802 TI - Interaction between cannabis consumption and childhood abuse in psychotic disorders: preliminary findings on the role of different patterns of cannabis use. AB - AIM: Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use. METHODS: Up to 231 individuals presenting for the first time to mental health services with psychotic disorders and 214 unaffected population controls from South London, United Kingdom, were recruited as part of the Genetics and Psychosis study. Information about history of cannabis use was collected using the Cannabis Experiences Questionnaire. Childhood physical and sexual abuse was assessed using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Neither lifetime cannabis use nor reported exposure to childhood abuse was associated with psychotic disorder when the other environmental variable was taken into account. Although the combination of the two risk factors raised the odds for psychosis by nearly three times (adjusted OR = 2.94, 95% CI: 1.44-6.02, P = 0.003), no evidence of interaction was found (adjusted OR = 1.46, 95% CI: -0.54 to 3.46, P = 0.152). Furthermore, the association of high-potency cannabis and daily consumption with psychosis was at least partially independent of the effect of childhood abuse. CONCLUSIONS: The heavy use of high-potency cannabis increases the risk of psychosis but, in addition, smoking of traditional resin (hash) and less than daily cannabis use may increase the risk for psychosis when combined with exposure to severe childhood abuse. PMID- 26560803 TI - The health status of a village population, 7 years after a major Q fever outbreak. AB - From 2007 to 2010, The Netherlands experienced a major Q fever outbreak with more than 4000 notifications. Previous studies suggested that Q fever patients could suffer long-term post-infection health impairments, especially fatigue. Our objective was to assess the Coxiella burnetii antibody prevalence and health status including fatigue, and assess their interrelationship in Herpen, a high incidence village, 7 years after the outbreak began. In 2014, we invited all 2161 adult inhabitants for a questionnaire and a C. burnetii indirect fluorescence antibody assay (IFA). The health status was measured with the Nijmegen Clinical Screening Instrument (NCSI), consisting of eight subdomains including fatigue. Of the 70.1% (1517/2161) participants, 33.8% (513/1517) were IFA positive. Of 147 participants who were IFA positive in 2007, 25 (17%) seroreverted and were now IFA negative. Not positive IFA status, but age <50 years, smoking and co morbidity, were independent risk factors for fatigue. Notified participants reported significantly more often fatigue (31/49, 63%) than non-notified IFA positive participants (150/451, 33%). Although fatigue is a common sequel after acute Q fever, in this community-based survey we found no difference in fatigue levels between participants with and without C. burnetii antibodies. PMID- 26560804 TI - Muller cell-mediated neurite outgrowth of the retinal ganglion cells via P2Y6 receptor signals. AB - Muller cells, the primary macroglia of the retina, support various functions of retinal ganglion cells (RGCs). Here, we demonstrate a nucleotide-mediated communication between these two types of cells, by which Muller cells control neurite outgrowth of RGCs by activation of P2 receptors such as P2Y6 . Cultured mouse RGCs had significantly enhanced neurite outgrowth when cultured with either cultured mouse Muller cells or conditioned medium derived from Muller cells, and this was completely inhibited by the nucleotide-degrading enzyme, apyrase. This increase in outgrowth was mimicked by exogenously applied nucleotides such as ATP, uridine triphosphate, and uridine diphosphate. Pharmacological and genetic analysis revealed that P2Y6 receptor in RGCs was responsible for the increased neurite outgrowth. P2Y6 receptor was expressed in the ganglion cell layer of the retina and in RGC primary cultures. High performance liquid chromatography has revealed that Muller cells constitutively release uridine triphosphate, which is immediately metabolized into uridine diphosphate, an endogenous agonist for P2Y6 receptor. In the in vitro ocular hypertension model (i.e., glaucoma model), neurite outgrowth in RGCs was significantly reduced, which was associated with a decrease in P2Y6 receptors. Taken together, Muller cells control neurite outgrowth of RGCs by activating P2 receptors such as P2Y6 receptor, and the receptor expression level might be down-regulated in glaucoma. Muller cells support various functions of retina including those of retinal ganglion cells (RGCs). Here, we report an importance of nucleotide-mediated communication between these two types of cells. Muller cells were found to release uridine diphosphate (UTD), uridine triphosphate (UTP), and activate P2Y6 receptors in RGCs, which was essential for neurite outgrowth of RGCs. In addition, P2Y6 receptors in RGCs were reduced in a glaucoma model in vitro, suggesting an involvement of their dysfunction in the pathogenesis of glaucoma. PMID- 26560805 TI - Working Life and Retirement Expectancies at Age 50 by Social Class: Period and Cohort Trends and Projections for Finland. AB - Objectives: The balance between the amount of time spent in work and in retirement underlies the long-term sustainability of the social security system. We examined socioeconomic differences in how increasing longevity is distributed between labor market statuses in Finland. Method: We used register data and the Sullivan method to analyze life expectancy at age 50 spent in different labor market statuses over the period 1989-2012 and across cohorts born in 1938-1953. We projected the future mortality and labor market participation rates of partially observed cohorts. Results: Both working life expectancy at age 50 and the share of remaining life spent in work have increased across periods following the recession of the early 1990s, and across successive cohorts. The trends were similar across the social classes, but there were large differences in the numbers of years spent in various states: for the most recent period and the youngest cohort, we find that compared with upper non-manual employees, male and female manual workers were expected to spend 3.6-3.7 fewer years in work, 1.7-4.7 fewer years in statutory retirement, and 3.2-3.9 more years in other forms of nonemployment. Discussion: Our finding that the share of remaining life at age 50 spent in work is increasing implies that pressure on the welfare system is not as severe as is commonly thought. PMID- 26560806 TI - Identifying consumer preferences for specific beef flavor characteristics in relation to cattle production and postmortem processing parameters. AB - Sensory analysis of ground LL samples representing 12 beef product categories was conducted in 3 different regions of the U.S. to identify flavor preferences of beef consumers. Treatments characterized production-related flavor differences associated with USDA grade, cattle type, finishing diet, growth enhancement, and postmortem aging method. Consumers (N=307) rated cooked samples for 12 flavors and overall flavor desirability. Samples were analyzed to determine fatty acid content. Volatile compounds produced by cooking were extracted and quantified. Overall, consumers preferred beef that rated high for beefy/brothy, buttery/beef fat, and sweet flavors and disliked beef with fishy, livery, gamey, and sour flavors. Flavor attributes of samples higher in intramuscular fat with greater amounts of monounsaturated fatty acids and lesser proportions of saturated, odd chain, omega-3, and trans fatty acids were preferred by consumers. Of the volatiles identified, diacetyl and acetoin were most closely correlated with desirable ratings for overall flavor and dimethyl sulfide was associated with an undesirable sour flavor. PMID- 26560807 TI - In vivo activity of cefquinome against Riemerella anatipestifer using the pericarditis model in the duck. AB - Cefquinome is a fourth-generation cephalosporin with broad-spectrum antibacterial activity, including activity against enteric gram-negative bacilli such as Riemerella anatipestifer. The pericarditis model was used to examine the pharmacodynamic characteristics of cefquinome against R. anatipestifer. Serum levels of cefquinome following the administration of different doses were determined by LC-MS/MS. Ducks with ca. 10(6) CFU/mL at the initiation of therapy were treated with cefquinome at doses that ranged from 0.0156 to 2 mg/kg of body weight/day (in 3, 6, 12, or 24 divided doses) for 24 h. The percentage of a 24-h dosing interval that the unbound serum cefquinome concentrations exceeded the MIC (fT > MIC) were the pharmacokinetic (PK)-pharmacodynamic (PD) parameter that best correlated with efficacy (R(2) 86.3% for R. anatipestifer, compared with 58.9% for the area under the concentration-time curve/MIC and 10.6% for peak/MIC). A sigmoid Emax model was used to estimate the magnitudes of the %fT > MIC associated with net bacterial stasis, a 1-log10 CFU reduction from baseline, and a 2-log10 CFU reduction from baseline; the corresponding values were (22.5 +/- 1.3) %, (35.2 +/- 4.5) %, and (42.4 +/- 2.7) %. These data showed that treatment with cefquinome results in marked antibacterial effects in vivo against R. anatipestifer and that the host's immunity may also play a key role in the anti infective therapy process. PMID- 26560808 TI - Cardboard/sawdust briquettes as biomass fuel: Physical-mechanical and thermal characteristics. AB - This paper elaborates experimental analysis of cardboard/sawdust briquettes as a viable option for biomass fuel. Physical-mechanical and thermal characteristics of cardboard/sawdust briquettes were investigated. The influence of the main parameters on heating content was also examined through an ANOVA and regression analysis, i.e. pressure influence (that was applied in a punch-and-die process), cardboard/sawdust ratio influence and finally drying temperature influence. In order to find the maximum heating value, minimum ash content and maximum compressive strength optimization were done. The optimal values obtained for the studied briquetting process parameters are a compression force of 588.6 kN, a sawdust mass of 46.66% and a drying temperature of 22 degrees C. According to the mathematical model obtained, these optimal values give a maximum higher heating value of 17.41 MJ/kg, a minimum ash content of 6.62% and a maximum compressive strength of 149.54 N/mm. Finally, Cardboard/sawdust briquettes showed potential for application as viable biomass fuel. PMID- 26560809 TI - Influence of shape and size of the particles on jigging separation of plastics mixture. AB - Plastics are popular for numerous applications due to their high versatility and favourable properties such as endurance, lightness and cheapness. Therefore the generation of plastic waste is constantly increasing, becoming one of the larger categories in municipal solid waste. Almost all plastic materials are recyclable, but for the recycling to be possible it is necessary to separate the different types of plastics. The aim of this research was to evaluate the performance of the jig separation of bi-component plastic mixtures. For this study six granulated plastics had been used: Polystyrene (PS), Polymethyl methacrylate (PMMA), Polyethylene Terephthalate (PET-S, PET-D) and Polyvinyl Chloride (PVC-M, PVC-D). Plastics mixtures were subjected to jigging in a laboratorial Denver mineral jig. The results showed that the quality of the jigging separation varies with the mixture, the density differences and with the size and shape of the particles. In the case of particles with more regular shapes the quality of separation of bi-component plastic mixtures improved with the increase of the particle size. For lamellar particles the influence of particle size was minimal. In general, the beneficiation of plastics with similar densities was not effective, since the separation efficiency was lower than 25%. However, in bi component plastic mixtures that join a low density plastic (PS) with a high density one (PMMA, PET-S, PET-D, PVC-M and PVC-D), the quality of the jigging separation was greatly improved. The PS grade in the sunk was less than 1% for all the plastic mixtures. Jigging proved to be an effective method for the separation of bi-component plastic mixtures. Jigging separation will be enhanced if the less dense plastic, that overflows, has a lamellar shape and if the denser plastic, that sinks, has a regular one. PMID- 26560810 TI - Prevalence of chronic kidney disease in a representative sample of the Polish population: results of the NATPOL 2011 survey. AB - BACKGROUND: Chronic kidney disease (CKD) has been proven to be a major risk factor of cardiovascular disease (CVD). Until now, data on the prevalence of CKD among adults in Poland were limited. The NATPOL 2011 survey is a cross-sectional observational study designed to assess the prevalence and control of CVD risk factors in Poland, and the first study capable of evaluating CKD prevalence in adult Polish citizens. METHODS: Serum creatinine concentration and the urine albumin-to-creatinine ratio (ACR) were measured in 2413 randomly selected participants (ages 18-79 years) from a national survey study. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m(2) or >=60 mL/min/1.73 m(2) with coexisting albuminuria (ACR >= 30 mg/g). Additionally, comorbidities and anthropometric and social factors related to the prevalence of CKD were analysed. RESULTS: The prevalence of CKD was estimated at 5.8% [95% confidence interval (95% CI) 4.6-7.2] using Chronic Kidney Disease Epidemiology Collaboration formula. The general prevalence was higher when the MDRD was applied [6.2% (95% CI 4.0-7.6)]. An eGFR <60 mL/min/1.73 m(2) was found in 1.9% (95% CI 1.5-2.5) of the studied population. This was accompanied by low awareness of this condition (14.9%). The frequency of albuminuria was estimated at 4.5% (95% CI 3.4-5.9). Diabetes mellitus (DM) and arterial hypertension (AH) were more frequent among respondents with diagnosed CKD compared with those without CKD [18.5 versus 4.5% (P < 0.001) and 67.8 versus 29.0% (P < 0.001) respectively]. DM and AH were, apart from increasing age, the two greatest risk factors of CKD. CONCLUSION: The estimated prevalence of CKD among adults in Poland is 5.8% (~1 724 960 patients). Its prevalence was lower than expected. CKD is more frequent in older subjects, smokers and people with comorbidities such as AH and DM. PMID- 26560811 TI - Endurance exercise and growth hormone improve bone formation in young and growth retarded chronic kidney disease rats. AB - BACKGROUND: Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. METHODS: In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. RESULTS: CKD related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. CONCLUSIONS: Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease. PMID- 26560813 TI - Electrically Tunable Bandgaps in Bilayer MoS2. AB - Artificial semiconductors with manufactured band structures have opened up many new applications in the field of optoelectronics. The emerging two-dimensional (2D) semiconductor materials, transition metal dichalcogenides (TMDs), cover a large range of bandgaps and have shown potential in high performance device applications. Interestingly, the ultrathin body and anisotropic material properties of the layered TMDs allow a wide range modification of their band structures by electric field, which is obviously desirable for many nanoelectronic and nanophotonic applications. Here, we demonstrate a continuous bandgap tuning in bilayer MoS2 using a dual-gated field-effect transistor (FET) and photoluminescence (PL) spectroscopy. Density functional theory (DFT) is employed to calculate the field dependent band structures, attributing the widely tunable bandgap to an interlayer direct bandgap transition. This unique electric field controlled spontaneous bandgap modulation approaching the limit of semiconductor-to-metal transition can open up a new field of not yet existing applications. PMID- 26560812 TI - Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation. AB - Vascular calcification, a pathologic response to defective calcium and phosphate homeostasis, is strongly associated with cardiovascular mortality and morbidity. In this study, we have observed that pyruvate dehydrogenase kinase 4 (PDK4) is upregulated and pyruvate dehydrogenase complex phosphorylation is increased in calcifying vascular smooth muscle cells (VSMCs) and in calcified vessels of patients with atherosclerosis, suggesting that PDK4 plays an important role in vascular calcification. Both genetic and pharmacological inhibition of PDK4 ameliorated the calcification in phosphate-treated VSMCs and aortic rings and in vitamin D3-treated mice. PDK4 augmented the osteogenic differentiation of VSMCs by phosphorylating SMAD1/5/8 via direct interaction, which enhances BMP2 signaling. Furthermore, increased expression of PDK4 in phosphate-treated VSMCs induced mitochondrial dysfunction followed by apoptosis. Taken together, our results show that upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification. PMID- 26560814 TI - Nobiletin, a Polymethoxylated Flavone, Inhibits Glioma Cell Growth and Migration via Arresting Cell Cycle and Suppressing MAPK and Akt Pathways. AB - Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3(') ,4(') hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20-100 um) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2 promoter-binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen-activated protein kinases, including p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen-activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme. PMID- 26560815 TI - Dental Press Journal of Orthodontics and QUALIS. PMID- 26560816 TI - The pursue of quality. PMID- 26560817 TI - An interview with Carlos Alberto Estevanell Tavares. PMID- 26560818 TI - Orthodontic decompensation in skeletal Class III malocclusion: redefining the amount of movement assessed by Cone-Beam Computed Tomography. AB - INTRODUCTION: Cone-Beam Computed Tomography (CBCT) is essential for tridimensional planning of orthognathic surgery, as it allows visualization and evaluation of bone structures and mineralized tissues. Tomographic slices allow evaluation of tooth inclination and individualization of movement performed during preoperative decompensation. The aim of this paper was to assess maxillary and mandibular incisors inclination pre and post orthodontic decompensation in skeletal Class III malocclusion. METHODS: The study was conducted on six individuals with skeletal Class III malocclusion, surgically treated, who had Cone-Beam Computed Tomographic scans obtained before and after orthodontic decompensation. On multiplanar reconstruction view, tomographic slices (axial, coronal and sagittal) were obtained on the long axis of each incisor. The sagittal slice was used for measurement taking, whereas the references used to assess tooth inclination were the long axis of maxillary teeth in relation to the palatal plane and the long axis of mandibular teeth in relation to the mandibular plane. RESULTS: There was significant variation in the inclination of incisors before and after orthodontic decompensation. This change was of greater magnitude in the mandibular arch, evidencing that natural compensation is more effective in this arch, thereby requiring more intensive decompensation. CONCLUSION: When routinely performed, the protocols of decompensation treatment in surgical individuals often result in intensive movements, which should be reevaluated, since the extent of movement predisposes to reduction in bone attachment levels and root length. PMID- 26560819 TI - Stability of smooth and rough mini-implants: clinical and biomechanical evaluation - an in vivostudy. AB - OBJECTIVE: To compare in vivo orthodontic mini-implants (MI) of smooth (machined) and rough (acid etched) surfaces, assessing primary and secondary stability. METHODS: Thirty-six (36) MI were inserted in the mandibles of six (6) dogs. Each animal received six (6) MI. In the right hemiarch, three (3) MI without surface treatment (smooth) were inserted, whereas in the left hemiarch, another three (3) MI with acid etched surfaces (rough) were inserted. The two distal MI in each hemiarch received an immediate load of 1.0 N for 16 weeks, whereas the MI in the mesial extremity was not subject to loading. Stability was measured by insertion and removal torque, initial and final mobility and by inter mini-implant distance. RESULTS: There was no statistical behavioral difference between smooth and rough MI. High insertion torque and reduced initial mobility were observed in all groups, as well as a reduction in removal torques in comparison with insertion torque. Rough MI presented higher removal torque and lower final mobility in comparison to smooth MI. MI did not remain static, with displacement of rough MI being smaller in comparison with smooth MI, but with no statistical difference. CONCLUSIONS: MI primary stability was greater than stability measured at removal. There was no difference in stability between smooth and rough MI when assessing mobility, displacement and insertion as well as removal torques. PMID- 26560820 TI - Dental and skeletal effects of combined headgear used alone or in association with rapid maxillary expansion. AB - OBJECTIVE: The aim of this study was to assess the effects of combined headgear used alone or in association with rapid maxillary expansion, as the first step for Class II malocclusion treatment. METHODS: The sample comprised 61 patients divided into three groups: Group 1, combined headgear (CH); Group 2, CH + rapid maxillary expansion (CH + RME); and Group 3, control (CG). In Group 1, patients were treated with combined headgear until Class I molar relationship was achieved. In Group 2, the protocol for headgear was the same; however, patients were previously subject to rapid maxillary expansion. RESULTS: Results showed distal displacement of maxillary molars for both experimental groups (p < 0.001), with distal tipping only in Group 1 (CH) (p < 0.001). There was restriction of forward maxillary growth in Group 2 (CH + RME) (p < 0.05) and clockwise rotation of the maxilla in Group 1 (CH) (p < 0.05). CONCLUSION: Based on the results, it is possible to suggest that treatment with both protocols was efficient; however, results were more significant for Group 2 (CH + RME) with less side effects. PMID- 26560821 TI - Influence of occlusal plane inclination and mandibular deviation on esthetics. AB - OBJECTIVE: The aim of this study was to assess the degree of perception of occlusal plane inclination and mandibular deviation in facial esthetics, assessed by laypeople, dentists and orthodontists. METHODS: A woman with 5.88 degrees of inclination and 5.54 mm of mandibular deviation was selected and, based on her original photograph, four new images were created correcting the deviations and creating more symmetric faces and smiles. Examiners assessed the images by means of a questionnaire. Their opinions were compared by qualitative and quantitative analyses. RESULTS: A total of 45 laypeople, 27 dentists and 31 orthodontists filled out the questionnaires. All groups were able to perceive the asymmetry; however, orthodontists were more sensitive, identifying asymmetries as from 4.32 degrees of occlusal plane inclination and 4.155 mm of mandibular deviation (p< 0.05). The other categories of evaluators identified asymmetries and assigned significantly lower grades, starting from 5.88 degrees of occlusal plane inclination and 5.54 mm of mandibular deviation (p< 0.05). CONCLUSION: Occlusal plane inclination and mandibular deviation were perceived by all groups, but orthodontists presented higher perception of deviations. PMID- 26560822 TI - Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review. AB - INTRODUCTION: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. OBJECTIVES: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. METHODS: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. RESULTS: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). CONCLUSIONS: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements. PMID- 26560823 TI - Effect of chlorhexidine varnish on gingival growth in orthodontic patients: a randomized prospective split-mouth study. AB - INTRODUCTION: Fixed orthodontic appliances patients suffer limitations on the effective control of biofilm by mechanical methods, bringing the need of a coadjutant in the control of inflammation and oral health improvement. OBJECTIVE: The aim of this prospective split-mouth blind study was to analyze the effect of a 40% chlorhexidine (CHX) varnish on gingival growth of patients with orthodontic fixed appliances. METHODS: Healthy teenage patients with fixed orthodontic appliances and increased gingival volume were recruited (n = 30). Each individual was his own control, having in the maxilla one control side and one treatment side. An application of varnishes occurred on the vestibular area of the upper premolars and first molar crowns, on the control side (placebo varnish) and on the experimental side (EC40(r) Biodentic CHX varnish). The varnishes and sides were randomly chosen and its identification and group was kept by a third party observer and it was not revealed to the researchers and participants until the end of study. In order to establish a baseline registration, digital photographs were taken by a trained photographer before varnish application at baseline (T0), as well as 14 days (T14) and 56 days (T56) after the application. The gingival volume was calculated indirectly using the vestibular areas (mm2) of the upper second premolars' clinical crowns by RapidSketch(r) software, at all study times. The data were analyzed using ANOVA and the Turkey-Krammer test. RESULTS: It was observed, in the final sample of 30 individuals, that at T0, the control and treatment groups were similar. At T14 and T56, a progressive reduction of the clinical crown area was seen in the control group, and an increase in the average area was detected in the experimental group (p < 0,05). CONCLUSIONS: The use of 40% CHX varnish decreases the gingival overgrowth in patients undergoing orthodontic treatment. Further studies are necessary to set the action time and frequency of application. PMID- 26560824 TI - Reliability of Bolton analysis evaluation in tridimensional virtual models. AB - OBJECTIVE: The present study aimed at evaluating the reliability of Bolton analysis in tridimensional virtual models, comparing it with the manual method carried out with dental casts. METHODS: The present investigation was performed using 56 pairs of dental casts produced from the dental arches of patients in perfect conditions and randomly selected from Universidade Federal da Bahia, School of Dentistry, Orthodontics Postgraduate Program. Manual measurements were obtained with the aid of a digital Cen-Tech 4"(r) caliper (Harpor Freight Tools, Calabasas, CA, USA). Subsequently, samples were digitized on 3Shape(r)R-700T scanner (Copenhagen, Denmark) and digital measures were obtained by Ortho Analyzer software. RESULTS: Data were subject to statistical analysis and results revealed that there were no statistically significant differences between measurements with p-values equal to p = 0.173 and p= 0.239 for total and anterior proportions, respectively. CONCLUSION: Based on these findings, it is possible to deduce that Bolton analysis performed on tridimensional virtual models is as reliable as measurements obtained from dental casts with satisfactory agreement. PMID- 26560825 TI - Efficiency of different protocols for enamel clean-up after bracket debonding: an in vitro study. AB - OBJECTIVE: This study aimed to assess the efficiency of six protocols for cleaning-up tooth enamel after bracket debonding. METHODS: A total of 60 premolars were divided into six groups, according to the tools used for clean-up: 12-blade bur at low speed (G12L), 12-blade bur at high speed (G12H), 30-blade bur at low speed (G30L), DU10CO ORTHO polisher (GDU), Renew System (GR) and Diagloss polisher (GD). Mean roughness (Ra) and mean roughness depth (Rz) of enamel surface were analyzed with a profilometer. Paired t-test was used to assess Ra and Rz before and after enamel clean-up. ANOVA/Tukey tests were used for intergroup comparison. The duration of removal procedures was recorded. The association between time and variation in enamel roughness (?Ra, ?Rz) were evaluated by Pearson's correlation test. Enamel topography was assessed by scanning electron microscopy (SEM). RESULTS: In Groups G12L and G12H, original enamel roughness did not change significantly. In Groups G30L, GDU, GR and GD, a smoother surface (p < 0.05) was found after clean-up. In Groups G30L and GD, the protocols used were more time-consuming than those used in the other groups. Negative and moderate correlation was observed between time and (?Ra, ?Rz); Ra and (?Ra, ?Rz); Rz (r = - 0.445, r = - 0.475, p < 0.01). CONCLUSION: All enamel clean-up protocols were efficient because they did not result in increased surface roughness. The longer the time spent performing the protocol, the lower the surface roughness. PMID- 26560826 TI - Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion. AB - OBJECTIVE: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one. METHODS: A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years old were assessed. Forty radiographs of Class I malocclusion individuals were matched by age with forty radiographs of individuals with mandibular Class II malocclusion. McNamara Jr., Ricketts, Downs and Jarabak's measurements were used for cephalometric evaluation. Data were submitted to descriptive and inferential statistical analysis by means of SPSS 20.0 statistical package. Student's t-test, Pearson correlation and intraclass correlation coefficient were used. A 95% confidence interval and 5% significance level were adopted to interpret the results. RESULTS: There were differences between groups. Oropharynx and nasopharynx sizes as well as mandibular position and length were found to be reduced in Class II individuals. There was a statistically significant positive correlation between the size of the oropharynx and Xi-Pm, Co-Gn and SNB measurements. In addition, the size of the nasopharynx was found to be correlated with Xi-Pm, Co-Gn, facial depth, SNB, facial axis and FMA. CONCLUSION: Individuals with mandibular Class II malocclusion were shown to have upper airways measurements diminished. There was a correlation between mandibular length and position and the size of oropharynx and nasopharynx. PMID- 26560827 TI - Parent-assessed quality of life among adolescents undergoing orthodontic treatment: a 12-month follow-up. AB - OBJECTIVE: To assess parents' and caregivers' view of the first twelve months of adolescents' orthodontic treatment with fixed appliances and to assess the evaluative properties of the Brazilian version of the Parental-Caregiver Perceptions Questionnaire (P-CPQ) in the orthodontic setting. METHODS: Data from a sample of 96 parents and caregivers of adolescents undergoing orthodontic treatment with fixed appliances were collected by means of P-CPQ. Assessments were performed before banding and bracket bonding (T1) and 12 months after placement of fixed appliances (T2). Statistical analysis included Wilcoxon signed rank test for the overall P-CPQ score and Bonferroni correction for P-CPQ subscales. The evaluative properties of the P-CPQ were assessed through responsiveness calculation and the minimally clinical important difference (MCID). RESULTS: Among the 96 participants, 76 were mothers of patients, 16 were fathers, and four were other family members. Adolescents' mean age was 11.49 +/- 0.50 years. Most families earned equal to or less than three times the Brazilian monthly minimum wage. There was significant improvement in the emotional and social well-being subscales (p< 0.001), which contributed to improve patient's overall quality of life (p< 0.001). Reductions in scores were associated with clinically meaningful moderate changes in the overall score as well as in the emotional and social well-being subscales. The MCID was 6.16 for the P-CPQ overall score. CONCLUSION: Parents and caregivers reported significant improvement in the quality of life of adolescents undergoing orthodontic treatment with fixed appliances. PMID- 26560829 TI - Agenesis of maxillary lateral incisor in an Angle Class II, Division 1 malocclusion patient. AB - The present case report describes the orthodontic treatment of a patient with agenesis of maxillary left lateral incisor and Angle Class II, Division 1 malocclusion. The patient also presented with maxillary midline deviation and inclination of the occlusal plane in the anterior region. Treatment objectives were: correction of sagittal relationship between the maxilla and the mandible; correction of midline deviation, so as to cause maxillary and mandibular midlines to coincide; correction of overbite and leveling of the occlusal plane, so as to create ideal conditions for esthetic rehabilitation of anterior teeth. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as a requirement for the title of certified by the BBO. PMID- 26560828 TI - Manual reduction of articular disc after traumatic extraction of mandibular third molar: a case report. AB - INTRODUCTION: Disc displacement without reduction with limited opening is an intracapsular biomechanical disorder involving the condyle-disc complex. With the mouth closed, the disc is in an anterior position in relation to the condylar head and does not reduce with mouth opening. This disorder is associated with persistent limited mandibular opening. CASE REPORT: The patient presented severe limitation to fully open the mouth, interfering in her ability to eat. Clinical examination also revealed maximum assisted jaw opening (passive stretch) with less than 40 mm of maximum interincisal opening. Magnetic resonance imaging was the method of choice to identify the temporomandibular disorders. CONCLUSION: By means of reporting this rare case of anterior disc displacement without reduction with limited opening, after traumatic extraction of a mandibular third molar, in which manual reduction of temporomandibular joint articular disc was performed, it was possible to prove that this technique is effective in the prompt restoration of mandibular movements. PMID- 26560830 TI - Dual embryonic origin of maxillary lateral incisors: clinical implications in patients with cleft lip and palate. AB - INTRODUCTION: Cleft lip and palate are craniofacial anomalies highly prevalent in the overall population. In oral clefts involving the alveolar ridge, variations of number, shape, size and position are observed in maxillary lateral incisors. The objective of this manuscript is to elucidate the embryonic origin of maxillary lateral incisors in order to understand the etiology of these variations.Contextualization: The hypothesis that orofacial clefts would split maxillary lateral incisor buds has been previously reported. However, recent studies showed that maxillary lateral incisors have dual embryonic origin, being partially formed by both the medial nasal process and the maxillary process. In other words, the mesial half of the lateral incisor seems to come from the medial nasal process while the distal half of the lateral incisor originates from the maxillary process. In cleft patients, these processes do not fuse, which results in different numerical and positional patterns for lateral incisors relating to the alveolar cleft. In addition to these considerations, this study proposes a nomenclature for maxillary lateral incisors in patients with cleft lip and palate, based on embryology and lateral incisors position in relation to the alveolar cleft. CONCLUSION: Embryological knowledge on the dual origin of maxillary lateral incisors and the use of a proper nomenclature for their numerical and positional variations renders appropriate communication among professionals and treatment planning easier, in addition to standardizing research analysis. PMID- 26560831 TI - Stereoselective Degradation and Molecular Ecological Mechanism of Chiral Pesticides Beta-Cypermethrin in Soils with Different pH Values. AB - For decades, pesticides have been widely used for agricultural activities around the world, and the environmental problems caused by these compounds have raised widespread concern. However, the different enantioselective behaviors of chiral pesticide enantiomers are often ignored. Here, the selective degradation patterns and mechanisms of chiral pesticide enantiomers were successfully investigated for the first time in the soils of three cultivation areas with different pH values. Beta-cypermethrin was chosen as the target analyte. We found that the degradation rates of the four isomers of beta-cypermethrin were different. We used stepwise regression equations between degradation rates and functional genes to quantitatively study their relationships. Quantitative response analysis revealed that different isomers have different equations even under identical conditions. The results of path analysis showed that a single functional gene can make different direct and indirect contributions to the degradation of different isomers. Finally, the high-throughput technology was used to analysis the genome of the three tested soils and then compared the main microbial communities in them. We have successfully devised a method to investigate the molecular biological mechanisms of the selective degradation behavior of chiral compounds, thus enabling us to better understand these mechanisms. PMID- 26560832 TI - Mutations in CACNA2D4 Cause Distinctive Retinal Dysfunction in Humans. PMID- 26560833 TI - Incidence and Characteristics of Cystoid Macular Edema after Cataract Surgery. PMID- 26560834 TI - Changing physical activity and sedentary behaviour in people with COPD. AB - People with chronic obstructive pulmonary disease (COPD) engage in low levels of physical activity (PA). Given the evidence for the health benefits associated with participating in 150 min of moderate-to-vigorous intensity PA each week, there is considerable interest in methods to increase PA in people with COPD. Studies to date have focused largely on exercise training and behavioural approaches, and many have demonstrated minimal, if any effect. An intermediate goal that focuses on reducing time spent in sedentary behaviour (SB) and increasing participation in light intensity PA is a more realistic goal in this population and offers a gateway to higher intensity PA. Although strategies that are capable of reducing time spent in SB in COPD are unknown, studies that have shown some increase in PA in this population often provide individualized goal setting, motivational interviewing and frequent contact with health-care professionals to provide advice regarding strategies to overcome barriers. Therefore, these approaches should be considered in interventions to reduce time in SB. There are a range of devices available to monitor time in SB for use in both clinical and research settings. To move this area forward, a theoretically informed and systematic approach to behaviour change is needed. The theoretical model, the 'behaviour change wheel', is described and an example is provided of how it can be applied to a person with COPD. PMID- 26560835 TI - Development of the field of structural physiology. AB - Electron crystallography is especially useful for studying the structure and function of membrane proteins - key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 A resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named "adhennels" based on structures analyzed using electron and X-ray crystallography. PMID- 26560837 TI - Muographic imaging with a multi-layered telescope and its application to the study of the subsurface structure of a volcano. AB - In conventional muography observations using two detectors for muon tracking, the accidental coincidence of vertical electromagnetic showers generates identical trajectories to the muon tracks. Although muography has favorable properties, which allow direct density measurements inside a volcano, the measured density is lower than the actual value due to these fortuitous trajectories. We performed muography of Usu volcano, and confirmed that, in comparison with a use of two detectors, background noise levels were reduced by more than one order of magnitude using seven detectors for selecting linear trajectories. The resultant muographic image showed a high-density region underneath the central region of Usu volcano. This picture is consistent with the magma intrusion model proposed in previous studies. To clarify the three-dimensional location and actual size of the detected high-density body, multidirectional muographic measurements are necessary. PMID- 26560836 TI - The unfolded protein response: the dawn of a new field. AB - Originating from cancer research in mammalian cultured cells, the entirely new field of the unfolded protein response (UPR) was born in 1988. The UPR is a transcriptional induction program coupled with intracellular signaling from the endoplasmic reticulum (ER) to the nucleus to maintain the homeostasis of the ER, an organelle which controls the quality of proteins destined for the secretory pathway. Extremely competitive analyses using the budding yeast Saccharomyces cerevisiae revealed that although signaling from both the ER and cell surface is initiated by activation of a transmembrane protein kinase, the mechanism downstream of ER-resident Ire1p, a sensor molecule of the UPR, is unique. Thus, unconventional spliceosome-independent mRNA splicing is utilized to produce the highly active transcription factor Hac1p. This is the autobiographical story of how a young and not yet independent scientist competed with a very famous full professor in the early days of UPR research, which ultimately lead to their sharing Lasker Basic Medical Research Award in 2014. PMID- 26560838 TI - Risk Factors for Long-Term Mortality and Amputation after Open and Endovascular Treatment of Acute Limb Ischemia. AB - BACKGROUND: Acute limb ischemia (ALI) is a highly morbid and fatal vascular emergency with little known about contemporary, long-term patient outcomes. The goal was to determine predictors of long-term mortality and amputation after open and endovascular treatment of ALI. METHODS: A retrospective review of ALI patients at a single institution from 2005 to 2011 was performed to determine the impact of revascularization technique on 5-year mortality and amputation. For each main outcome 2 multivariable models were developed; the first adjusted for preoperative clinical presentation and procedure type, the second also adjusted for postoperative adverse events (AEs). RESULTS: A total of 445 limbs in 411 patients were treated for ALI. Interventions included surgical thrombectomy (48%), emergent bypass (18%), and endovascular revascularization (34%). Mean age was 68 +/- 15 years, 54% were male, and 23% had cancer. Most patients presented with Rutherford classification IIa (54%) or IIb (39%). The etiology of ALI included embolism (27%), in situ thrombosis (28%), thrombosed bypass grafts (32%), and thrombosed stents (13%). Patients treated with open procedures had significantly more advanced ischemia and higher rates of postoperative respiratory failure, whereas patients undergoing endovascular interventions had higher rates of technical failure. Rates of postprocedural bleeding and cardiac events were similar between both treatments. Excluding Rutherford class III patients (n = 12), overall 5-year mortality was 54% (stratified by treatment, 65% for thrombectomy, 63% for bypass, and 36% for endovascular, P < 0.001); 5-year amputation was 28% (stratified by treatment, 18% for thrombectomy, 27% for bypass, and 17% for endovascular, P = 0.042). Adjusting for comorbidities, patient presentation, AEs, and treatment method, the risk of mortality increased with age (hazard ratio [HR] = 1.04, P < 0.001), female gender (HR = 1.50, P = 0.031), cancer (HR = 2.19, P < 0.001), fasciotomy (HR = 1.69, P = 0.204) in situ thrombosis or embolic etiology (HR = 1.73, P = 0.007), cardiac AEs (HR = 2.25, P < 0.001), respiratory failure (HR = 2.72, P < 0.001), renal failure (HR = 4.70, P < 0.001), and hemorrhagic events (HR = 2.25, P = 0.003). Risk of amputation increased with advanced ischemia (Rutherford IIb compared with IIa, HR = 2.57, P < 0.001), thrombosed bypass etiology (HR = 3.53, P = 0.002), open revascularization (OR; HR = 1.95, P = 0.022), and technical failure of primary intervention (HR = 6.01, P < 0.001). CONCLUSIONS: After the treatment of ALI, long-term mortality and amputation rates were greater in patients treated with open techniques; OR patients presented with a higher number of comorbidities and advanced ischemia, while also experiencing a higher rate of major postoperative complications. Overall, mortality rates remained high and were most strongly associated with baseline comorbidities, acuity of presentation, and perioperative AEs, particularly respiratory failure. Comparatively, amputation risk was most highly associated with advanced ischemia, thrombosed bypass, and failure of the initial revascularization procedure. PMID- 26560839 TI - Tryptophan oxidation catabolite, N-formylkynurenine, in photo degraded cell culture medium results in reduced cell culture performance. AB - Chemically defined media have been widely used in the biopharmaceutical industry to enhance cell culture productivities and ensure process robustness. These media, which are quite complex, often contain a mixture of many components such as vitamins, amino acids, metals and other chemicals. Some of these components are known to be sensitive to various stress factors including photodegradation. Previous work has shown that small changes in impurity concentrations induced by these potential stresses can have a large impact on the cell culture process including growth and product quality attributes. Furthermore, it has been shown to be difficult to detect these modifications analytically due to the complexity of the cell culture media and the trace level of the degradant products. Here, we describe work performed to identify the specific chemical(s) in photodegraded medium that affect cell culture performance. First, we developed a model system capable of detecting changes in cell culture performance. Second, we used these data and applied an LC-MS analytical technique to characterize the cell culture media and identify degradant products which affect cell culture performance. Riboflavin limitation and N-formylkynurenine (NFK), a tryptophan oxidation catabolite, were identified as chemicals which results in a reduction in cell culture performance. PMID- 26560840 TI - The looming tide of nontuberculous mycobacterial infections in Portugal and Brazil. AB - Nontuberculous mycobacteria (NTM) are widely disseminated in the environment and an emerging cause of infectious diseases worldwide. Their remarkable natural resistance to disinfectants and antibiotics and an ability to survive under low nutrient conditions allows NTM to colonize and persist in man-made environments such as household and hospital water distribution systems. This overlap between human and NTM environments afforded new opportunities for human exposure, and for expression of their often neglected and underestimated pathogenic potential. Some risk factors predisposing to NTM disease have been identified and are mainly associated with immune fragilities of the human host. However, infections in apparently immunocompetent persons are also increasingly reported. The purpose of this review is to bring attention to this emerging health problem in Portugal and Brazil and to emphasize the urgent need for increased surveillance and more comprehensive epidemiological data in both countries, where such information is scarce and seriously thwarts the adoption of proper preventive strategies and therapeutic options. PMID- 26560841 TI - Refractory depression with catatonic features was remitted with administration of intravenous dopamine and consequent bupropion as maintenance treatment. PMID- 26560842 TI - The oral health of people with chronic schizophrenia: A neglected public health burden. AB - OBJECTIVE: People with chronic schizophrenia have high rates of physical ill health such as heart disease. However, there has been less attention to the issue of poor oral health including dental caries (tooth decay) and periodontal (gum) disease, although both have consequences for quality of life and systemic physical health. We therefore measured tooth decay and gum disease in Malaysians with schizophrenia. METHODS: We recruited long-stay inpatients with schizophrenia from June to October 2014. Four dental specialists assessed oral health using the decayed-missing-filled teeth index, the Community Periodontal Index of Treatment Needs and the Debris Index of the Simplified Oral Hygiene Index. Results were compared with the 2010 Oral Health survey of the general Malaysian population. RESULTS: A total of 543 patients participated (66.7% males, 33.3% females; mean age = 54.8 years [standard deviation = 16.0]) with a mean illness duration of 18.4 years (standard deviation = 17.1). The mean decayed-missing-filled teeth was 20.5 (standard deviation = 9.9), almost double that of the general population (11.7). Higher decayed-missing-filled teeth scores were associated with both older age (p < 0.001) and longer illness duration (p = 0.048). Only 1% (n = 6) had healthy gums. Levels of decay and periodontal disease were greatest in those aged between 45 and 64 years, coinciding with the onset of tooth loss. CONCLUSION: Dental disease in people with schizophrenia deserves the same attention as other comorbid physical illness. The disparity in oral health is most marked for dental decay. Possible interventions include oral health assessments using standard checklists designed for non-dental personnel, help with oral hygiene, management of iatrogenic dry mouth and early dental referral. PMID- 26560843 TI - Mental disorders and distress: Associations with demographics, remoteness and socioeconomic deprivation of area of residence across Australia. AB - OBJECTIVES: Australian policy-making needs better information on socio geographical associations with needs for mental health care. We explored two national surveys for information on disparities in rates of mental disorders and psychological distress. METHODS: Secondary data analysis using the 2011/2012 National Health Survey and 2007 National Survey of Mental Health and Wellbeing. Key data were the Kessler 10 scores in adults in the National Health Survey (n = 12,332) and the National Survey of Mental Health and Wellbeing (n = 6558) and interview-assessed disorder rates in the National Survey of Mental Health and Wellbeing. Estimation of prevalence of distress and disorders for sub-populations defined by geographic and socioeconomic status of area was followed by investigation of area effects adjusting for age and gender. RESULTS: Overall, approximately one person in 10 reported recent psychological distress at high/very-high level, this finding varying more than twofold depending on socioeconomic status of area with 16.1%, 13.3%, 12.0%, 8.4% and 6.9% affected in the most to least disadvantaged quintiles, respectively, across Australia in 2011/2012. In the most disadvantaged quintile, the percentage (24.4%) with mental disorders was 50% higher than that in the least disadvantaged quintile (16.9%) in 2007, so this trend was less strong than for Kessler10 distress. CONCLUSION: These results suggest that disparities in mental health status in Australia based on socioeconomic characteristics of area are substantial and persisting. Whether considering 1-year mental disorders or 30-day psychological distress, these occur more commonly in areas with socioeconomic disadvantage. The association is stronger for Kessler10 scores suggesting that Kessler10 scores behaved more like a complex composite indicator of the presence of mental and subthreshold disorders, inadequate treatment and other responses to stressors linked to socioeconomic disadvantage. To reduce the observed disparities, what might be characterised as a 'Whole of Government' approach is needed, addressing elements of socioeconomic disadvantage and the demonstrable and significant inequities in treatment provision. PMID- 26560844 TI - Enhanced Laser Desorption/Ionization Mass Spectrometric Detection of Gold Nanoparticles in Biological Samples Using the Synergy between Added Matrix and the Gold Core. AB - Laser desorption/ionization mass spectrometry (LDI-MS) has been used to detect gold nanoparticles (AuNPs) in biological samples, such as cells and tissues, by ionizing their attached monolayer ligands. Many NP-attached ligands, however, are difficult to ionize by LDI, making it impossible to track these NPs in biological samples. In this work, we demonstrate that concentrations of matrix-assisted LDI (MALDI) matrices an order of magnitude below the values typically used in MALDI can facilitate the selective detection of AuNPs with these ligands, even in samples as complex as cell lysate. This enhanced sensitivity arises from a synergistic relationship between the gold core and the matrix that helps to selectively ionize ligands attached to the AuNPs. PMID- 26560846 TI - [Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures]. AB - The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance. PMID- 26560845 TI - Immunogenicity of anti-TNF biologic agents in the treatment of rheumatoid arthritis. AB - INTRODUCTION: The use of biologic disease-modifying anti-rheumatic drugs (DMARDs), including therapeutic antibodies, antibody fragments and protein constructs that target key mediators in the pathophysiology of rheumatoid arthritis (RA), has improved the chance of achieving low disease activity and clinical remission. However, individual patients respond differently to biologic DMARD therapy, particularly the tumor necrosis factor (TNF) inhibitors. AREAS COVERED: While the variation of clinical response may be related to pharmacogenetic and other unknown factors, immunogenicity associated with some of these agents may contribute in part to a lack of efficacy and immune-mediated side effects. Timely detection of immunogenicity may avoid continued administration of ineffective treatment, and reduce unnecessary risks and costs. Access to and appropriate implementation of clinically validated drug level assays is required. EXPERT OPINION: There are currently no evidence-based recommendations to guide biologic therapy on the basis of drug level and immunogenicity testing but as more data become available and better tests are developed, a strategy of immunopharmacologic guidance to individualize treatment of RA will emerge. The potential benefits of this approach must be balanced against the costs of monitoring, and further research is required. PMID- 26560847 TI - [Characteristic Features of Urinary Incontinence--Diagnostic Investigation in Geriatric Patients]. AB - Urinary incontinence is a common medical and social problem in elderly people. It leads to a massive reduction in the quality of life of affected persons and their dependants and causes an enormous socio-economic burden, which will increase significantly within the next years and decades as the age structure of the German population changes. Successful treatment of urinary incontinence in the elderly requires a good pathophysiological understanding of the underlying problem as well as individually tailored diagnostic procedures, which must be oriented at the patient's wishes, the social environment and the resulting therapeutic consequences. This especially applies to persons with symptoms of dementia. Comorbidities such as diabetes mellitus, reduced mobility and a medication-induced decrease in cognitive function play a major role in the severity of urgency and urinary incontinence in the elderly. Also the frequently described concomitant diagnosis of urinary tract infection must be exactly evaluated. Before antibiotic treatment is given, it should be clarified if the patient suffers from "harmless" bacteriuria or a urinary tract infection requiring treatment. Patients with an age-associated decrease in brain power must be diagnosed quite carefully, because these patients may potentially be harmed by pharmacological treatment for overactive bladder syndrome. PMID- 26560848 TI - The divergent impact of COMT Val158Met on executive function in children with and without attention-deficit/hyperactivity disorder. AB - Children with attention-deficit/hyperactivity disorder (ADHD) usually display deficits in executive function (EF), which are primarily mediated by prefrontal cortex (PFC). The functional polymorphism of catechol-O-methyltransferase (COMT), Val158Met (rs4680), leads to observed polymorphic differences in the degradation of dopamine within PFC. This study aimed to explore the effect of rs4680 on EF using case-control design. In addition, considering the dynamic development of EF, we also attempted to investigate whether this genetic influence changes during development or not. A total of 597 ADHD children and 154 unaffected controls were recruited. The EF was evaluated using Rey-Osterrieth complex figure test (RCFT), trail making test (TMT) and Stroop color and word test for working memory, shifting and inhibition. Association between genotype and EF was analyzed using analysis of covariance (ancova). The results showed significant interaction effect of genotype and ADHD diagnosis on RCFT performance (P < 0.001). However, the associated genotypes between ADHD and controls were divergent. In ADHD, the Met carriers performed better than the Val homozygotes on detail immediate [(10.38 +/- 6.90) vs. (9.33 +/- 6.92), P = 0.007] and detail delay [(9.96 +/- 6.86) vs. (8.86 +/- 6.89), P = 0.004], while Val homozygotes showed better performance compared with Met carrier controls [for detail immediate (14.55 +/- 6.18) vs. (11.10 +/- 6.45), P<0.001; for detail delay (14.31 +/- 5.96) vs. (11.31 +/- 6.96), P = 0.001]. We did not find significant interaction between genetic variant and development. COMT Val158Met (rs4680) may have divergent effect on working memory in ADHD children compared with healthy controls. PMID- 26560849 TI - anti-Diradical Formation in 1,3-Dipolar Cycloadditions of Nitrile Oxides to Acetylenes. AB - By means of high level quantum chemical calculations (B2PLYPD and CCSD(T)), the mechanisms of the reaction of nitrile oxides with alkenes and alkynes were investigated. We were able to show that in the case of alkenes, regardless of the chosen substituents, the concerted mechanism is always energetically favored as compared to a two-step process, which runs through an anti-diradical species. In the case of alkynes, the concerted mechanism is favored only for the reaction of alkyl-substituted acetylenes. For aryl-substituted acetylenes, the activation barrier toward the anti-diradical is equal to or lower than the activation barrier of the concerted reaction. This reversal of the reaction paths is not only limited to nitrile oxides as dipolarophiles. Conditions favoring the anti diradical path are the presence of a triple bond in both the 1,3-dipole and the dipolarophile and additionally an aryl substituent attached to the alkyne. The featured energy relationships between the reaction paths are able to explain the experimentally observed byproducts of the reaction of nitrile oxides with arylacetylenes. The discovered differences for the preferred reaction path of 1,3 dipolar cycloadditions to acetylenes should be of considerable interest to a broader field of chemists. PMID- 26560850 TI - Both foliar and residual applications of herbicides that inhibit amino acid biosynthesis induce alternative respiration and aerobic fermentation in pea roots. AB - The objective of this work was to ascertain whether there is a general pattern of carbon allocation and utilisation in plants following herbicide supply, independent of the site of application: sprayed on leaves or supplied to nutrient solution. The herbicides studied were the amino acid biosynthesis-inhibiting herbicides (ABIH): glyphosate, an inhibitor of aromatic amino acid biosynthesis, and imazamox, an inhibitor of branched-chain amino acid biosynthesis. All treated plants showed impaired carbon metabolism; carbohydrate accumulation was detected in both leaves and roots of the treated plants. The accumulation in roots was due to lack of use of available sugars as growth was arrested, which elicited soluble carbohydrate accumulation in the leaves due to a decrease in sink strength. Under aerobic conditions, ethanol fermentative metabolism was enhanced in roots of the treated plants. This fermentative response was not related to a change in total respiration rates or cytochrome respiratory capacity, but an increase in alternative oxidase capacity was detected. Pyruvate accumulation was detected after most of the herbicide treatments. These results demonstrate that both ABIH induce the less-efficient, ATP-producing pathways, namely fermentation and alternative respiration, by increasing the key metabolite, pyruvate. The plant response was similar not only for the two ABIH but also after foliar or residual application. PMID- 26560851 TI - Synthesis of Highly Substituted Racemic and Enantioenriched Allenylsilanes via Copper-Catalyzed Hydrosilylation of (Z)-2-Alken-4-ynoates with Silylboronate. AB - Copper-catalyzed highly efficient hydrosilylation reaction of enynoates was developed. Under simple reaction conditions, various di-, tri-, and tetrasubstituted racemic allene products could be obtained in high yields. The asymmetric 1,6-addition of silyl group to the (Z)-2-alken-4-ynoates could be achieved under mild reaction conditions to afford the silyl-substituted enantioenriched chiral allene products in good yields and with high enantioselectivities. PMID- 26560852 TI - Detection of eye blink artifacts from single prefrontal channel electroencephalogram. AB - Eye blinks are one of the most influential artifact sources in electroencephalogram (EEG) recorded from frontal channels, and thereby detecting and rejecting eye blink artifacts is regarded as an essential procedure for improving the quality of EEG data. In this paper, a novel method to detect eye blink artifacts from a single-channel frontal EEG signal was proposed by combining digital filters with a rule-based decision system, and its performance was validated using an EEG dataset recorded from 24 healthy participants. The proposed method has two main advantages over the conventional methods. First, it uses single-channel EEG data without the need for electrooculogram references. Therefore, this method could be particularly useful in brain-computer interface applications using headband-type wearable EEG devices with a few frontal EEG channels. Second, this method could estimate the ranges of eye blink artifacts accurately. Our experimental results demonstrated that the artifact range estimated using our method was more accurate than that from the conventional methods, and thus, the overall accuracy of detecting epochs contaminated by eye blink artifacts was markedly increased as compared to conventional methods. The MATLAB package of our library source codes and sample data, named Eyeblink Master, is open for free download. PMID- 26560853 TI - Clinical evaluation and therapeutic monitoring value of serum tumor markers in lung cancer. AB - BACKGROUND: Tumor markers CYFRA21-1, CEA, NSE, CA125, pro-GRP and SCC are routinely used for lung cancer. However, there has been no systematic evaluation of these markers in the same cohort. The aim of this study was to evaluate the diagnostic and therapeutic monitoring value of these markers. METHODS: The levels of 6 serum tumor markers were measured in 392 patients, including 308 patients with non-small cell lung cancer (NSCLC) and 84 with small cell lung cancer (SCLC), and 116 patients with benign lung diseases and 144 healthy controls. 34 patients were followed up after operation and chemotherapy. Multiple logistic models and receiver operating characteristic (ROC) curves were used to evaluate their diagnostic value. RESULTS: CEA, NSE, CA125 and pro-GRP in SCLC, and CYFRA21 1 as well as CEA in NSCLC, were higher than those in control groups. The level of CEA and CA125 were related to the clinical stages of NSCLC. Pro-GRP was significantly increased in extensive disease (ED) compared with limited disease (LD) in SCLC. CYFRA21-1 was reduced after the third and fifth treatment cycle respectively in patients who undergoing operation and without operation. NSE and pro-GRP were reduced significantly after the second and third treatment cycles, respectively. CONCLUSIONS: CEA, NSE, CA125 and pro-GRP could serve as biomarkers for SCLC, and CEA and CYFRA21-1 could serve as biomarkers for NSCLC. Pro-GRP, CA125 and CEA were related to the clinical stages of lung cancer. CYFRA21-1, NSE and pro-GRP could be used for monitoring the effect of chemotherapy. PMID- 26560854 TI - The role of hypoxia in pancreatic cancer: a potential therapeutic target? AB - One of the key factors that correlates with poor survival of patients with pancreatic cancer is the extent of hypoxic areas within the tumor tissue. The adaptation of pancreatic cancer cells to limited oxygen delivery promotes the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development, which resist in most cases adjuvant therapies following tumor resection. In this article, the authors summarize the evidence demonstrating the significance of hypoxia in pancreatic cancer pathogenesis and discuss the possible hypoxia-induced mechanisms underlying its aggressive nature. We then conclude with promising strategies that target hypoxia adapted pancreatic cancer cells. PMID- 26560855 TI - Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies. AB - Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads. PMID- 26560856 TI - Application of the Steady-State Variable Nutation Angle Method for Faster Determinations of Long T 1s-An Approach Useful for the Design of Hyperpolarized MR Molecular Probes. AB - In the dissolution-dynamic nuclear polarization technique, molecular probes with long T 1s are preferred. 13C nuclei of small molecules with no directly bonded protons or sp(3 13)C nuclei with proton positions substituted by deuterons may fulfill this requirement. The T 1 determination of such new molecular probes is crucial for the success of the hyperpolarized observation. Although the inversion recovery approach remained by and large the standard for T 1 measurements, we show here that the steady-state variable nutation angle approach is faster and may be better suited for the determination of relatively long T 1s in thermal equilibrium. Specifically, the T 1 of a new molecular probe, [uniformly labeled (UL)-13C6, UL-2H8]2-deoxy-d-glucose, is determined here and compared to that of [UL-13C6, UL-2H7]d-glucose. PMID- 26560857 TI - Frequency of three prothrombotic polymorphisms among Syrian population: factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T. AB - BACKGROUND: Thrombophilia is a multi-factorial disorder caused by inherited and acquired factors. Among the inherited factors are factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphisms (SNPs). AIM: The main aim of this study was to assess the incidence of these three SNPs in the Syrian population. SUBJECTS AND METHODS: A total of 200 unrelated healthy Syrians (100 males and 100 females) were recruited. RESULTS: The prevalence of factor V G1691A, prothrombin G20210A and MTHFR C677T SNPs among Syrians is 11.5%, 2.5% and 84.5%, respectively. Prevalence of factor V G1691A and prothrombin G20210A SNPs among apparently healthy Syrian individuals is very high. CONCLUSION: To the best of the authors knowledge, the Syrian population harbours the highest prevalence of the MTHFR C677T polymorphism compared to all other populations reported so far. PMID- 26560858 TI - Subwavelength imaging through ion-beam-induced upconversion. AB - The combination of an optical microscope and a luminescent probe plays a pivotal role in biological imaging because it allows for probing subcellular structures. However, the optical resolutions are largely constrained by Abbe's diffraction limit, and the common dye probes often suffer from photobleaching. Here we present a new method for subwavelength imaging by combining lanthanide-doped upconversion nanocrystals with the ionoluminescence imaging technique. We experimentally observed that the ion beam can be used as a new form of excitation source to induce photon upconversion in lanthanide-doped nanocrystals. This approach enables luminescence imaging and simultaneous mapping of cellular structures with a spatial resolution of sub-30 nm. PMID- 26560859 TI - Effects of combining transarterial chemoembolization with percutaneous microwave coagulation therapy for hepatocellular carcinoma abutting the diaphragm. AB - OBJECTIVE: This study aims to explore the clinical effectiveness of a combination therapy of transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) in treating hepatocellular carcinoma (HCC) abutting the diaphragm. MATERIAL AND METHODS: Six cases with HCC were treated with TACE followed by PMCT one month later with the aid of artificial pneumothorax. RESULTS: CT/MRI revealed complete necrosis in the tumor lesions and the treated tumor margins (>= 5 mm). Serum alpha-fetoprotein (AFP) levels markedly declined in patients who originally had higher serum AFP levels. Postoperative complications such as fever, mild hepatic dysfunction and pleural effusion were alleviated within a short period of time. All patients were closely monitored through follow-up; all patients survived, except for one patient who received a liver transplantation. CONCLUSIONS: As lesions are either invisible or poorly visible in sonography, determining an effective treatment for HCC abutting the diaphragm remains a particular challenge. TACE and PMCT combined therapy with the aid of artificial pneumothorax proved to be an available treatment option. PMID- 26560860 TI - Helicobacter pylori among patients with symptoms of gastroduodenal ulcer disease in rural Uganda. AB - INTRODUCTION: To meet key millennium development goals, the rural population needs to be reached for health assessment and service delivery. Gastroduodenal ulcer disease is a common ailment affecting the health of people in Uganda. A cross-sectional study was conducted at Bwera Hospital in Kasese district of western Uganda, to establish the prevalence and predisposing factors of Helicobacter pylori among gastroduodenal ulcer disease patients. METHODS: A sample of 174 patients with symptoms of gastroduodenal ulcer disease was purposively obtained. Using two laboratory test methods, the prevalence of H. pylori among these patients was determined. A structured questionnaire was administered to participants to establish their demographic background and selected aspects of their lifestyle. Finally, the results obtained by enzyme linked immunosorbent assay (ELISA) and immunochromatographic rapid test (IRT) were compared. RESULTS: We established the prevalence of H. pylori as 29.9% (52/174) by ELISA and 37.4% (65/174) by IRT. Cigarette smoking, poor sanitation, and lack of formal education were the significant predisposing factors with p values <0.05. The two tests gave identical results in 87.9% of the patients. DISCUSSION: The prevalence of H. pylori by IRT and ELISA test methods was similar to what has been reported elsewhere in developed countries; but was lower than previously reported in developing countries including Uganda. The previous studies in Uganda were carried out in the urban population and on young children; and some used antibody-detection methods only, therefore leading to different prevalence as a result of difference in study population and methods. PMID- 26560861 TI - A trial with IgY chicken antibodies to eradicate faecal carriage of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum beta-lactamases. AB - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is an emerging therapeutic challenge, especially in the treatment of urinary tract infections. Following an outbreak of CTX-M-15 Klebsiella pneumoniae in Uppsala, Sweden, an orphan drug trial on IgY chicken antibodies was undertaken in an attempt to eradicate faecal carriage of ESBL-producing K. pneumoniae and Escherichia coli. METHODS: Hens were immunised with epitopes from freeze-dried, whole-cell bacteria (ESBL-producing K. pneumoniae and E. coli) and recombinant proteins of two K. pneumoniae fimbriae subunits (fimH and mrkD). The egg yolks were processed according to good manufacturing practice and the product was stored at-20 degrees C until used. Using an internal database from the outbreak and the regular laboratory database, faecal carriers were identified and recruited from May 2005 to December 2013. The participants were randomised in a placebo-controlled 1:1 manner. RESULTS: From 749 eligible patients, 327 (44%) had deceased, and only 91 (12%) were recruited and signed the informed consent. In the initial screening performed using the polymerase chain reaction, 24 participants were ESBL positive and subsequently randomised and treated with either the study drug or a placebo. The study was powered for 124 participants. Because of a very high dropout rate, the study was prematurely terminated. From the outbreak cohort (n=247), only eight patients were screened, and only one was positive with the outbreak strain in faeces. CONCLUSIONS: The present study design, using IgY chicken antibodies for the eradication of ESBL-producing K. pneumonia and E. coli, was ineffective in reaching its goal due to high mortality and other factors resulting in a low inclusion rate. Spontaneous eradication of ESBL-producing bacteria was frequently observed in recruited participants, which is consistent with previous reports. PMID- 26560862 TI - Optical Properties of Photovoltaic Organic-Inorganic Lead Halide Perovskites. AB - Over the last several years, organic-inorganic lead halide perovskites have rapidly emerged as a new photovoltaic contender. Although energy conversion efficiency above 20% has now been certified, improved understanding of the material properties contributing to these high performance levels may allow the progression to even higher efficiency, stable cells. The optical properties of these new materials are important not only to device design but also because of the insight they provide into less directly accessible properties, including energy-band structures, binding energies, and likely impact of excitons, as well as into absorption and inverse radiative recombination processes. PMID- 26560863 TI - Cheers, proost, saude: Cultural, contextual and psychological factors of wine and beer consumption in Portugal and in the Netherlands. AB - Wine and beer consumption are an integral part of European culture: Southern Europe is associated with wine and Northern Europe is associated with beer. When consumed in moderation, these alcoholic beverages can be part of a balanced and healthy diet. In the 1990s, non-alcoholic beer (NAB), which has no cultural roots, became available in the market. This review identifies determinants for consumption of wine, beer, and NAB, using data on consumption patterns from Portugal and the Netherlands. Since the 1960s the image of Portugal as a wine country declined, whereas the image of the Netherlands as a beer country remained stable. In each country beer is now the most consumed alcoholic beverage and is mainly a men's beverage, whereas wine is the second most consumed and is consumed by both genders. Cultural differences define Portuguese as "outdoors, everyday drinkers", within a meal context, and Dutch as "at home, weekend drinkers." Wine is perceived as the healthiest beverage, followed by NAB, and regular beer. Motivation for consumption is related to context: wine for special occasions, beer for informal occasions, and NAB for occasions when alcohol is not convenient. Moderate wine and beer consumption seems to be surrounded by positive emotions. This review is relevant for public health, for industry market strategies, and identifies opportunities of future research on drinking behaviour. PMID- 26560864 TI - Effect of Mutations on the Binding of Kanamycin-B to RNA Hairpins Derived from the Mycobacterium tuberculosis Ribosomal A-Site. AB - Kanamycin is an aminoglycoside antibiotic used in the treatment of drug-resistant tuberculosis. Mutations at the rRNA A-site have been associated with kanamycin resistance in Mycobacterium tuberculosis clinical isolates. Understanding the effect of these mutations on the conformation of the M. tuberculosis A-site is critical for understanding the mechanisms of antibiotic resistance in M. tuberculosis. In this work, we have studied RNA hairpins derived from the M. tuberculosis A-site, the wild type and three mutants at the following positions (M. tuberculosis/Escherichia coli numbering): A1400/1408 -> G, C1401/1409 -> U, and the double mutant G1483/1491 C1401/1409 -> UA. Specifically, we used circular dichroism, ultraviolet spectroscopy, and fluorescence spectroscopy to characterize the conformation, stability, and binding affinity of kanamycin-B and other aminoglycoside antibiotics for these RNA hairpins. Our results show that the mutations affect the conformation of the decoding site, with the mutations at position 1401/1409 resulting in significant destabilizations. Interestingly, the mutants bind paromomycin with weaker affinity than the wild type, but they bind kanamycin-B with similar affinity than the wild type. The results suggest that the presence of mutations does not prevent kanamycin-B from binding. Instead, kanamycin may promote different interactions with a third partner in the mutants compared to the wild type. Furthermore, our results with longer and shorter hairpins suggest that the region of the A-site that varies among organisms may have modulating effects on the binding and interactions of the A-site. PMID- 26560865 TI - Real-Time Classification of Hand Motions Using Ultrasound Imaging of Forearm Muscles. AB - Surface electromyography (sEMG) has been the predominant method for sensing electrical activity for a number of applications involving muscle-computer interfaces, including myoelectric control of prostheses and rehabilitation robots. Ultrasound imaging for sensing mechanical deformation of functional muscle compartments can overcome several limitations of sEMG, including the inability to differentiate between deep contiguous muscle compartments, low signal-to-noise ratio, and lack of a robust graded signal. The objective of this study was to evaluate the feasibility of real-time graded control using a computationally efficient method to differentiate between complex hand motions based on ultrasound imaging of forearm muscles. Dynamic ultrasound images of the forearm muscles were obtained from six able-bodied volunteers and analyzed to map muscle activity based on the deformation of the contracting muscles during different hand motions. Each participant performed 15 different hand motions, including digit flexion, different grips (i.e., power grasp and pinch grip), and grips in combination with wrist pronation. During the training phase, we generated a database of activity patterns corresponding to different hand motions for each participant. During the testing phase, novel activity patterns were classified using a nearest neighbor classification algorithm based on that database. The average classification accuracy was 91%. Real-time image-based control of a virtual hand showed an average classification accuracy of 92%. Our results demonstrate the feasibility of using ultrasound imaging as a robust muscle-computer interface. Potential clinical applications include control of multiarticulated prosthetic hands, stroke rehabilitation, and fundamental investigations of motor control and biomechanics. PMID- 26560866 TI - Six Conductivity Values to Use in the Bidomain Model of Cardiac Tissue. AB - GOAL: The aim of this work is to produce a consistent set of six conductivity values for use in the bidomain model of cardiac tissue. METHODS: Studies in 2007 by Hooks et al. and in 2009 by Caldwell et al. have found that, in the directions longitudinal:transverse:normal (l:t:n) to the cardiac fibers, ratios of bulk conductivities and conduction velocities are each approximately in the ratio 4:2:1. These results are used here as the basis for a method that can find sets of six normalized bidomain conductivity values. RESULTS: It is found that the ratios involving transverse and normal conductivities are quite consistent, allowing new light to be shed on conductivity in the normal direction. For example, it is found that the ratio of transverse to normal conductivity is much greater in the intracellular (i) than the extracellular (e) domain. Using parameter values from experimental studies leads to the proposal of a new nominal six conductivity dataset: gil=2.4, gel=2.4, git=0.35, get=2.0, gin=0.08, and gen=1.1 (all in mS/cm). CONCLUSION: When it is used to model partial thickness ischaemia, this dataset produces epicardial potential distributions in accord with experimental studies in an animal model. It is, therefore, suggested that the dataset is suitable for use in numerical simulations. SIGNIFICANCE: Since the bidomain approach is the most commonly used method for modeling cardiac electrophysiological phenomena, new information about conductivity in the normal direction, as well as a consistent set of six conductivity values, is valuable for researchers who perform simulation studies. PMID- 26560867 TI - An Obstructive Sleep Apnea Detection Approach Using a Discriminative Hidden Markov Model From ECG Signals. AB - Obstructive sleep apnea (OSA) syndrome is a common sleep disorder suffered by an increasing number of people worldwide. As an alternative to polysomnography (PSG) for OSA diagnosis, the automatic OSA detection methods used in the current practice mainly concentrate on feature extraction and classifier selection based on collected physiological signals. However, one common limitation in these methods is that the temporal dependence of signals are usually ignored, which may result in critical information loss for OSA diagnosis. In this study, we propose a novel OSA detection approach based on ECG signals by considering temporal dependence within segmented signals. A discriminative hidden Markov model (HMM) and corresponding parameter estimation algorithms are provided. In addition, subject-specific transition probabilities within the model are employed to characterize the subject-to-subject differences of potential OSA patients. To validate our approach, 70 recordings obtained from the Physionet Apnea-ECG database were used. Accuracies of 97.1% for per-recording classification and 86.2% for per-segment OSA detection with satisfactory sensitivity and specificity were achieved. Compared with other existing methods that simply ignore the temporal dependence of signals, the proposed HMM-based detection approach delivers more satisfactory detection performance and could be extended to other disease diagnosis applications. PMID- 26560868 TI - Deep Transcranial Magnetic Stimulation: Modeling of Different Coil Configurations. AB - OBJECTIVE: Deep transcranial magnetic stimulation (dTMS) has been recently used in several clinical studies as diagnostic and therapeutic tool. However, electric field (E) distributions induced in the brain by dTMS are still unknown. This paper provides a characterization of the induced E distributions in the brain of a realistic human model due to 16 different coil configurations. METHODS: The scalar potential finite-element method was used to calculate the E distributions differentiating the brain structures, e.g., cortex, white matter, anterior cingulated cortex, cerebellum, thalamus, hypothalamus, nucleus accumbens, amygdale, and hippocampus. RESULTS: Our results support that the double cone coils and the large diameter circular coils are more prone to activate deeper brain structures but are also characterized by a reduced focality on the surface of the cortex, with the consequent possible counter effect of stimulating regions not of interest. The Hesed coils, although their ability to reach deep brain tissues is lower, seem to be more able to reduce the effect on other brain regions where the stimulation is undesired. CONCLUSION: All the coil configurations resulted subjected to a depth-focality tradeoff. SIGNIFICANCE: Since there is not a configuration that is capable of achieving a stimulation both deep and focal, the selection of the most suitable coil settings for a specific clinical application should be based on a balanced evaluation between these two different needs. PMID- 26560870 TI - Advancing research in NeuroAIDS using collaboration and public data sharing. AB - In this issue of BMC Medical Genomics Griffin et al. present a user-friendly and freely accessible HIV-associated neurocognitive disorder (HAND) genomic database that compiles viral (HIV-1) genetic sequences and other relevant clinical and treatment data. We discuss the benefits and caveats of public data sharing in NeuroAIDS research, while emphasizing the importance of such novel initiatives for advancing knowledge. PMID- 26560869 TI - Simulating the Interacting Effects of Intraspecific Variation, Disturbance, and Competition on Climate-Driven Range Shifts in Trees. AB - Climate change is expected to favor shifts in plant distributions; some such shifts are already being observed along elevation gradients. However, the rate of such shifts may be limited by their ability to reach newly suitable areas and by competition from resident species. The degree of local adaptation and genetic variation may also play a role in the interaction between migrants and residents by affecting relative fitness. We used a simulation model to explore the interacting effects of dispersal, fecundity, disturbance, and genetic variation on range-edge dynamics between a pair of demographically similar tree species. Ideal climate for an individual is determined by genotype. The simulated landscape undergoes an 80-year period of climate change in which climate bands shift upslope; subsequently, climate is held constant for 300 years. The presence of a high-elevation competitor caused a significant lag in the range shift of the low-elevation species relative to competition-free scenarios. Increases in fecundity and dispersal distance both helped to speed up the replacement of the high-elevation species by the low-elevation species at their range boundary. While some disturbance scenarios facilitated this transition, frequent canopy disturbance inhibited colonization by removing reproductive adults and led to range contractions in both species. Differences between dispersal scenarios were more pronounced when disturbance was frequent (15 vs. 25 year return interval) and dispersal was limited. When the high-elevation species lacked genetic variation, its range was more-easily invaded by the low-elevation species, while a similar lack of variation in the low-elevation species inhibited colonization but only when this lack of variation decreased the fitness of the affected species near the range boundary. Our model results support the importance of measuring and including dispersal/fecundity, disturbance type and frequency, and genetic variation when assessing the potential for range shifts and species vulnerability to climate change. PMID- 26560871 TI - The pitfalls of bedside regional cerebral oxygen saturation in the early stage of post cardiac arrest. AB - It remains uncertain whether neuromonitoring reliably predicts outcome in adult post-cardiac arrest patients in the early stage treated with therapeutic hypothermia. Recent reports demonstrated a regional cerebral oxygen saturation of cardiac arrest patients on hospital arrival could predict their neurological outcome. There has been little discussion about the significance of regional cerebral oxygen saturation in patients with post-cardiac arrest syndrome. Amplitude-integrated electroencephalography monitoring may also provide early prognostic information for post-cardiac arrest syndrome. However, even when the initial electroencephalography is flat after the return of spontaneous circulation, good neurological outcome may still be obtainable if the electroencephalography shifts to a continuous pattern. The electroencephalography varied from flat to various patterns, such as flat, epileptic, or continuous during the first 24 h, while regional cerebral oxygen saturation levels varied even when the electroencephalography was flat. It is therefore difficult to estimate whether regional cerebral oxygen saturation accurately indicates the coupling of cerebral blood flow and metabolism in the early stage after cardiac arrest. Careful assessment of prognosis is necessary when relying solely on regional cerebral oxygen saturation as a single monitoring modality. PMID- 26560872 TI - Direct factor Xa inhibitor edoxaban: from bench to clinical practice. AB - Edoxaban is a direct factor Xa inhibitor and has become the fourth direct oral anticoagulant (DOAC) approved for stroke prevention in atrial fibrillation (AF) and for treatment and secondary prevention of venous thromboembolism (VTE). This review provides an overview of the key characteristics of edoxaban and clinical evaluation program leading to regulatory approval. Approval for AF and VTE treatment was based on large phase III randomized controlled trials that showed that edoxaban reduces the risk of bleeding compared with warfarin and provides similar protection against thromboembolism. Edoxaban is the second once-daily DOAC, is tested in a reduced dose for patients with a moderate renal impairment, body weight of <=60 kg or concomitant use of p-glycoprotein inhibitors and thereby is a valuable addition to the therapeutic arsenal of modern anticoagulation. For AF regulatory approval in the USA is limited to patients with a creatinine clearance of 15-95 ml/min. Another limitation is the need for initial parenteral anticoagulation with heparin in treatment of acute VTE. PMID- 26560873 TI - Evaluating DNA Extraction Methods for Community Profiling of Pig Hindgut Microbial Community. AB - Recovery of high quality PCR-amplifiable DNA has been the general minimal requirement for DNA extraction methods for bulk molecular analysis. However, modern high through-put community profiling technologies are more sensitive to representativeness and reproducibility of DNA extraction method. Here, we assess the impact of three DNA extraction methods (with different levels of extraction harshness) for assessing hindgut microbiomes from pigs fed with different diets (with different physical properties). DNA extraction from each sample was performed in three technical replicates for each extraction method and sequenced by 16S rRNA amplicon sequencing. Host was the primary driver of molecular sequencing outcomes, particularly on samples analysed by wheat based diets, but higher variability, with one failed extraction occurred on samples from a barley fed pig. Based on these results, an effective method will enable reproducible and quality outcomes on a range of samples, whereas an ineffective method will fail to generate extract, but host (rather than extraction method) remains the primary factor. PMID- 26560875 TI - miR-20a regulates expression of the iron exporter ferroportin in lung cancer. AB - Ferroportin (FPN) exports iron from duodenal enterocytes, macrophages, and hepatocytes to maintain systemic iron homeostasis. In addition, FPN is expressed in various cancer cells. Here, we show that in lung cancer, FPN expression is regulated by miR-20a. Within the FPN-3'-untranslated region (3'UTR), we identify and experimentally validate three evolutionarily conserved target sites for the microRNA (miRNA) members of the miR-17 seed family, including miR-20a. Our analysis of RNA sequencing data from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) revealed that FPN messenger RNA (mRNA) levels are significantly decreased in tumor compared to matched healthy tissue, while miR-20a levels are increased. A significant negative correlation of miR-20a and FPN expression was observed. Functional studies further demonstrate that FPN is post-transcriptionally regulated by miR-20a in non-small cell lung cancer (NSCLC) cells and that overexpression or knockdown of miR-20a or FPN affects NSCLC proliferation and colony formation. Taken together, our data suggest that increased expression of miR-20 in lung cancer may decrease iron export, leading to intracellular iron retention, which, in turn, favors cell proliferation. KEY MESSAGES: miR-20a controls expression of the iron exporter ferroportin (FPN) by binding to highly conserved target sites in its 3'UTR. Expression of miR-20a is inversely correlated to FPN in lung cancer. Low FPN expression stimulates proliferation and colony formation of non-small cell lung cancer (NSCLC) cells, possibly by increasing iron availability for cancer cell proliferation. PMID- 26560874 TI - Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer. AB - INTRODUCTION: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the non-specific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. METHODS: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. RESULTS AND CONCLUSION: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies. PMID- 26560876 TI - Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus. AB - AIM: Type 2 diabetes mellitus (T2D) is associated with gray matter atrophy. Adiposity and physical inactivity are risk factors for T2D and brain atrophy. We studied whether the associations of T2D with total gray matter volume (GMV) and hippocampal volume (HV) are dependent on obesity and physical activity. MATERIALS AND METHODS: In this cross-sectional study, we measured waist-hip ratio (WHR), body mass index (BMI), mean steps/day and brain volumes in a community dwelling cohort of people with and without T2D. Using multivariable linear regression, we examined whether WHR, BMI and physical activity mediated or modified the association between T2D, GMV and HV. RESULTS: There were 258 participants with (mean age 67 +/- 7 years) and 302 without (mean age 72 +/- 7 years) T2D. Adjusting for age, sex and intracranial volume, T2D was independently associated with lower total GMV (p = 0.001) and HV (p<0.001), greater WHR (p<0.001) and BMI (p<0.001), and lower mean steps/day (p = 0.002). After adjusting for covariates, the inclusion of BMI and mean steps/day did not significantly affect the T2D-GMV association, but WHR attenuated it by 32% while remaining independently associated with lower GMV (p<0.01). The T2D-HV association was minimally changed by the addition of BMI, steps/day or WHR in the model. No statistical interactions were observed between T2D and measures of obesity and physical activity in explaining brain volumes. CONCLUSIONS: Abdominal obesity or its downstream effects may partially mediate the adverse effect of T2D on brain atrophy. This requires confirmation in longitudinal studies. PMID- 26560877 TI - Investigational drugs for treating anal cancer and future perspectives. AB - INTRODUCTION: Anal cancer is a relatively rare malignancy which comprises about 2.5% of all digestive system malignancies in the United States. The majority of cases are squamous cell carcinoma which is closely related to human papilloma virus (HPV) infection. Despite high cure rates with chemoradiation alone, 10 - 20% of patients do develop metastatic disease with little data to guide their treatment. AREAS COVERED: In this review article, the authors describe the current standard treatment of early and advanced squamous cell carcinoma of the anal canal based on published data. The authors then describe the new approaches to the disease, focusing on new radio sensitizing agents, systemic targeted drugs and immunotherapy. EXPERT OPINION: The authors believe that current standard treatment options for squamous cell carcinoma of the anal canal are well defined with acceptable results. However the major challenge in the treatment of anal cancer is the lack of randomized or even large single arm Phase II trials due to rarity of the disease, especially in the metastatic disease. But we are slowly making progress. Currently, the most promising areas of research are immunotherapy, targeted therapy and even HPV prevention. We are eagerly anticipating the results of these studies in order to expand the treatment armamentarium. PMID- 26560878 TI - Primary silicone oil tamponade and internal limiting membrane peeling for retinal detachment due to macular hole in highly myopic eyes with chorioretinal atrophy. AB - BACKGROUND: Retinal detachment (RD) secondary to macular hole (MH) is a common complication in highly myopic eyes, usually leading to a poor visual prognosis. The purpose of this study was to evaluate the surgical outcome of silicone oil (SO) tamponade and internal limiting membrane (ILM) peeling in the treatment of RD caused by MH (MHRD) in highly myopic eyes with chorioretinal atrophy, and to identify clinical factors associated with the anatomical outcomes. METHODS: We retrospectively reviewed 21 eyes of 21 highly myopic patients affected by RD secondary to MH and chorioretinal atrophy. All eyes were treated with pars plana vitrectomy (PPV) with ILM peeling and SO tamponade. Anatomical success was defined as reattachment of the retina with the closure of the MH, as assessed by optical coherence tomography (OCT), after SO removal. Logistic regression was performed to determine the clinical factors influencing anatomical success. RESULTS: The mean patient age was 59.95 years [standard deviation (SD), 10.39; range, 34-77 years] and the mean axial length was 30.58 mm (SD, 1.52; range, 27.99-34.51 mm). After the first surgical procedure, the anatomical success rate was 61.9% (13 eyes in 21 eyes), with initial retinal attachment of 16 eyes (76.2%). A second surgical approach was performed for the five eyes with persistent or recurrent RD, and the final retinal reattachment rate was 100% (21/21). Logistic regression analysis showed that no specific factors were significantly associated with anatomical success. CONCLUSIONS: Primary silicone oil tamponade and ILM peeling can be a practical treatment for repairing MHRD in highly myopic eyes with chorioretinal atrophy. PMID- 26560879 TI - Germination and extrusion as combined processes for reducing phytates and increasing phenolics content and antioxidant capacity of Oryza sativa L. whole grain flours. AB - Whole rice (WR) products with low phytic acid (PA) content and enhanced bio functional components were obtained by the combination of germination and extrusion processes. Germination conditions (24 h - 35 degrees C), with a previous soaking process (24 h - 20 degrees C), were chosen according to the remnant PA content and germination rate. Specific mechanical energy consumption, expansion, sensorial and mechanical hardness, specific volume, solubility, water absorption, free phenolic content (FPC) and antioxidant capacity were evaluated. Results indicated that 175 degrees C and 14 g 100 g(-1) of moisture were the most appropriate conditions to obtain expanded products and precooked flours based on germinated WR. Selected extruded product presented less PA content (821.6 9 +/- 10.3 versus 695.2 0 +/- 1.6 mg 100 g(-1)) and higher Fe bio accessibility, FPC (45.2 9 +/- 1.61 versus 66.3 5 +/- 3.35 mg GAE g(-1)) and antioxidant capacity compared with WR (34.9 5 +/- 0.8 versus 54.6 3 +/- 1.6 umol trolox g(-1)). Combining germination-extrusion processes could be a strategy to obtain expanded products or precooked flours based on WR with enhanced health benefits. PMID- 26560880 TI - Re-launch of PulMiCC trial to discover the true effect of pulmonary metastasectomy on survival in advanced colorectal cancer. PMID- 26560881 TI - A faithful JAGGED1 haploinsufficiency mouse model of arteriohepatic dysplasia (Alagille syndrome) after all. PMID- 26560882 TI - JC polyomavirus in the aetiology and pathophysiology of glial tumours. AB - Glial brain tumours with their poor prognosis, limited treatment modalities and unclear detailed pathophysiology represent a significant health concern. The purpose of the current study was to investigate and describe the possible role of the human polyomavirus JC as an underlying cancerogenic or co-cancerogenic factor in the complex processes of glial tumour induction and development. Samples from 101 patients with glial tumours were obtained during neurosurgical tumour resection. Small tissue pieces were taken from several areas of the histologically verified solid tumour core. Biopsies were used for DNA extraction and subsequent amplification reactions of sequences from the JC viral genome. Real-time polymerase chain reaction was used for detection and quantification of its non-coding control region (NCCR) and gene encoding the regulatory protein Large T antigen (LT). An average of 37.6% of all patients was found to be LT positive, whereas only 6.9% tested positive for NCCR. The analysis of the results demonstrated significant variance between the determined LT prevalence and the rate for NCCR, with a low starting copy number in all positive samples and threshold cycles in the range of 36 to 42 representing viral load in the range from 10 to 1000 copies/MUl. The results most probably indicate incomplete JC viral replication. Under such conditions, mutations in the host cell genome may be accumulated due to interference of the virus with the host cell machinery, and eventually malignant transformation may occur. PMID- 26560883 TI - Identifying and recruiting smokers for preoperative smoking cessation--a systematic review of methods reported in published studies. AB - BACKGROUND: Smoking cessation before surgery reduces postoperative complications, and the benefit is positively associated with the duration of being abstinent before a surgical procedure. A key issue in providing preoperative smoking cessation support is to identify people who smoke as early as possible before elective surgery. This review aims to summarise methods used to identify and recruit smokers awaiting elective surgery. METHODS: We searched MEDLINE, EMBASE, CINAHL, and PsycINFO, and references of relevant reviews (up to May 2014) to identify prospective studies that evaluated preoperative smoking cessation programmes. One reviewer extracted and a second reviewer checked data from the included studies. Data extracted from included studies were presented in tables and narratively described. RESULTS: We included 32 relevant studies, including 18 randomised controlled trials (RCTs) and 14 non-randomised studies (NRS). Smokers were recruited at preoperative clinics (n = 18), from surgery waiting lists (n = 6), or by general practitioners (n = 1), and the recruitment methods were not explicitly described in seven studies. Time points of preoperative recruitment of smokers was unclear in four studies, less than 4 weeks before surgery in 17 studies, and at least 4 weeks before surgery in only 11 studies. The recruitment rate tended to be lower in RCTs (median 58.2 %, range 9.1 to 90.9 %) than that in NRS (median 99.1 %, range 12.3 to 100 %) and lower in preoperative clinic-based RCTs (median 54.4 %, range 9.1 to 82.4 %) than that in waiting list-based RCTs (median 70.1 %, range 36.8 to 85.0 %). Smokers were recruited at least 4 weeks before surgery in four of the six waiting list-based studies and in only three of the 18 preoperative clinic-based studies. CONCLUSIONS: Published studies often inadequately described the methods for recruiting smokers into preoperative smoking cessation programmes. Although smoking cessation at any time is beneficial, many programmes recruited smokers at times very close to scheduled surgery so that the benefit of preoperative smoking cessation may have not been fully effected. Optimal delivery of preoperative smoking cessation remains challenging, and further research is required to develop effective preoperative cessation programmes for smokers awaiting elective operations. PMID- 26560884 TI - Quantifying and Mapping Global Data Poverty. AB - Digital information technologies, such as the Internet, mobile phones and social media, provide vast amounts of data for decision-making and resource management. However, access to these technologies, as well as their associated software and training materials, is not evenly distributed: since the 1990s there has been concern about a "Digital Divide" between the data-rich and the data-poor. We present an innovative metric for evaluating international variations in access to digital data: the Data Poverty Index (DPI). The DPI is based on Internet speeds, numbers of computer owners and Internet users, mobile phone ownership and network coverage, as well as provision of higher education. The datasets used to produce the DPI are provided annually for almost all the countries of the world and can be freely downloaded. The index that we present in this 'proof of concept' study is the first to quantify and visualise the problem of global data poverty, using the most recent datasets, for 2013. The effects of severe data poverty, particularly limited access to geoinformatic data, free software and online training materials, are discussed in the context of sustainable development and disaster risk reduction. The DPI highlights countries where support is needed for improving access to the Internet and for the provision of training in geoinfomatics. We conclude that the DPI is of value as a potential metric for monitoring the Sustainable Development Goals of the Sendai Framework for Disaster Risk Reduction. PMID- 26560885 TI - Comparison of the use of ventricular access devices and ventriculosubgaleal shunts in posthaemorrhagic hydrocephalus: systematic review and meta-analysis. AB - INTRODUCTION: Ventricular access devices (VAD) and ventriculosubgaleal shunts (VSGS) are currently both used as temporising devices to affect CSF drainage in neonatal posthaemorrhagic hydrocephalus (PHH), without clear evidence of superiority of either procedure. In this systematic review and meta-analysis, we compared the VSGS and VAD regarding complication rates, ventriculoperitoneal shunt conversion and infection rates, and mortality and long-term disability. METHODS: The review was registered with the PROSPERO international prospective register of systematic reviews (registration number CRD42015019750) and was conducted in accordance with PRISMA guidelines. RESULTS AND CONCLUSIONS: The literature search of five databases identified 338 publications, of which 5 met the inclusion criteria. All were retrospective cohort studies (evidence class 3b and 4). A significantly lower proportion of patients with a VSGS required CSF tapping compared to patients with a VAD (log OR -4.43, 95% CI -6.14 to -2.72). No other significant differences between the VAD and VSGS were identified in their rates of infection (log OR 0.03, 95% CI -0.77 to 0.84), obstruction (log OR 1.25, 95% CI -0.21 to 2.71), ventriculoperitoneal shunt dependence (log OR -0.06, 95% CI -0.93 to 0.82), subsequent shunt infection (log OR 0.23, 95% CI -0.61 to 1.06), mortality (log OR 0.37, 95% CI -0.95 to 1.70) or long-term disability (p = 0.9). In all studies, there was a lack of standardised criteria, variations between surgeons in heterogeneous cohorts of limited sample size and a lack of neurodevelopmental follow-up. This affirms the importance of an ongoing multicentre, prospective pilot study comparing these two temporising procedures to enable a more robust comparison. PMID- 26560886 TI - Dose-Response Association Between Psychological Distress and Risk of Completed Suicide in the General Population. PMID- 26560888 TI - Interventions to facilitate shared decision making to address antibiotic use for acute respiratory infections in primary care. AB - BACKGROUND: Shared decision making is an important component of patient-centred care. It is a set of communication and evidence-based practice skills that elicits patients' expectations, clarifies any misperceptions and discusses the best available evidence for benefits and harms of treatment. Acute respiratory infections (ARIs) are one of the most common reasons for consulting in primary care and obtaining prescriptions for antibiotics. However, antibiotics offer few benefits for ARIs, and their excessive use contributes to antibiotic resistance - an evolving public health crisis. Greater explicit consideration of the benefit harm trade-off within shared decision making may reduce antibiotic prescribing for ARIs in primary care. OBJECTIVES: To assess whether interventions that aim to facilitate shared decision making increase or reduce antibiotic prescribing for ARIs in primary care. SEARCH METHODS: We searched CENTRAL (2014, Issue 11), MEDLINE (1946 to November week 3, 2014), EMBASE (2010 to December 2014) and Web of Science (1985 to December 2014). We searched for other published, unpublished or ongoing trials by searching bibliographies of published articles, personal communication with key trial authors and content experts, and by searching trial registries at the National Institutes of Health and the World Health Organization. SELECTION CRITERIA: Randomised controlled trials (RCTs) (individual level or cluster-randomised), which evaluated the effectiveness of interventions that promote shared decision making (as the focus or a component of the intervention) about antibiotic prescribing for ARIs in primary care. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. Antibiotic prescribing was the primary outcome, and secondary outcomes included clinically important adverse endpoints (e.g. re-consultations, hospital admissions, mortality) and process measures (e.g. patient satisfaction). We assessed the risk of bias of all included trials and the quality of evidence. We contacted trial authors to obtain missing information where available. MAIN RESULTS: We identified 10 published reports of nine original RCTs (one report was a long-term follow-up of the original trial) in over 1100 primary care doctors and around 492,000 patients.The main risk of bias came from participants in most studies knowing whether they had received the intervention or not, and we downgraded the rating of the quality of evidence because of this.We meta-analysed data using a random-effects model on the primary and key secondary outcomes and formally assessed heterogeneity. Remaining outcomes are presented narratively.There is moderate quality evidence that interventions that aim to facilitate shared decision making reduce antibiotic use for ARIs in primary care (immediately after or within six weeks of the consultation), compared with usual care, from 47% to 29%: risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55 to 0.68. Reduction in antibiotic prescribing occurred without an increase in patient initiated re-consultations (RR 0.87, 95% CI 0.74 to 1.03, moderate quality evidence) or a decrease in patient satisfaction with the consultation (OR 0.86, 95% CI 0.57 to 1.30, low quality evidence). There were insufficient data to assess the effects of the intervention on sustained reduction in antibiotic prescribing, adverse clinical outcomes (such as hospital admission, incidence of pneumonia and mortality), or measures of patient and caregiver involvement in shared decision making (such as satisfaction with the consultation; regret or conflict with the decision made; or treatment compliance following the decision). No studies assessed antibiotic resistance in colonising or infective organisms. AUTHORS' CONCLUSIONS: Interventions that aim to facilitate shared decision making reduce antibiotic prescribing in primary care in the short term. Effects on longer-term rates of prescribing are uncertain and more evidence is needed to determine how any sustained reduction in antibiotic prescribing affects hospital admission, pneumonia and death. PMID- 26560887 TI - Ruthenium Complex "Light Switches" that are Selective for Different G-Quadruplex Structures. AB - Recognition and regulation of G-quadruplex nucleic acid structures is an important goal for the development of chemical tools and medicinal agents. The addition of a bromo-substituent to the dipyridylphenazine (dppz) ligands in the photophysical "light switch", [Ru(bpy)2 dppz](2+) , and the photochemical "light switch", [Ru(bpy)2 dmdppz](2+) , creates compounds with increased selectivity for an intermolecular parallel G-quadruplex and the mixed-hybrid G-quadruplex, respectively. When [Ru(bpy)2 dppz-Br](2+) and [Ru(bpy)2 dmdppz-Br](2+) are incubated with the G-quadruplexes, they have a stabilizing effect on the DNA structures. Activation of [Ru(bpy)2 dmdppz-Br](2+) with light results in covalent adduct formation with the DNA. These complexes demonstrate that subtle chemical modifications of Ru(II) complexes can alter G-quadruplex selectivity, and could be useful for the rational design of in vivo G-quadruplex probes. PMID- 26560889 TI - Essentiality drives the orientation bias of bacterial genes in a continuous manner. AB - Studies had found that bacterial genes are preferentially located on the leading strands. Subsequently, the preferences of essential genes and highly expressed genes were compared by classifying all genes into four groups, which showed that the former has an exclusive influence on orientation. However, only some functional classes of essential genes have this orientation bias. Nevertheless, previous studies only performed comparative analyzes by differentiating the orientation bias extent of two types of genes. Thus, it is unclear whether the influence of essentiality on strand bias works continuously. Herein, we found a significant correlation between essentiality and orientation bias extent in 19 of 21 analyzed bacterial genomes, based on quantitative measurement of gene essentiality (or fitness). The correlation coefficient was much higher than that derived from binary essentiality measures (essential or non-essential). This suggested that genes with relatively lower essentiality, i.e., conditionally essential genes, also have some orientation bias, although it is weaker than that of absolutely essential genes. The results demonstrated the continuous influence of essentiality on orientation bias and provided details on this visible structural feature of bacterial genomes. It also proved that Geptop and IFIM could serve as useful resources of bacterial gene essentiality, particularly for quantitative analysis. PMID- 26560890 TI - Social Organization in Parasitic Flatworms--Four Additional Echinostomoid Trematodes Have a Soldier Caste and One Does Not. AB - Complex societies where individuals exhibit division of labor with physical polymorphism, behavioral specialization, and caste formation have evolved several times throughout the animal kingdom. Recently, such complex sociality has been recognized in digenean trematodes; evidence is limited to 6 marine species. Hence, the extent to which a soldier caste is present throughout the Trematoda is sparsely documented, and there are no studies detailing the structure of a species lacking such a social structure. Here we examine colony structure for an additional 5 echinostomoid species, 4 of which infect the marine snail Cerithidea californica and 1 (Echinostoma liei) that infects the freshwater snail Biomphalaria glabrata . For all species, we present redia morphology (pharynx and body size) and the distribution of individuals of different castes throughout the snail body. When morphological evidence indicated the presence of a soldier caste, we assessed behavior by measuring attack rates of the different morphs toward heterospecific trematodes. Our findings indicate that each of the 4 species from C. californica have a permanent soldier caste while E. liei does not. The observed intra- and inter-specific variation of caste structure for those species with soldiers, and the documentation of colony structure for a species explicitly lacking permanent soldiers, emphasizes the diverse nature of trematode sociality and the promise of the group to permit comparative investigations of the evolution and ecology of sociality. PMID- 26560891 TI - Calcareous Bio-Concretions in the Northern Adriatic Sea: Habitat Types, Environmental Factors that Influence Habitat Distributions, and Predictive Modeling. AB - Habitat classifications provide guidelines for mapping and comparing marine resources across geographic regions. Calcareous bio-concretions and their associated biota have not been exhaustively categorized. Furthermore, for management and conservation purposes, species and habitat mapping is critical. Recently, several developments have occurred in the field of predictive habitat modeling, and multiple methods are available. In this study, we defined the habitats constituting northern Adriatic biogenic reefs and created a predictive habitat distribution model. We used an updated dataset of the epibenthic assemblages to define the habitats, which we verified using the fuzzy k-means (FKM) clustering method. Redundancy analysis was employed to model the relationships between the environmental descriptors and the FKM membership grades. Predictive modelling was carried out to map habitats across the basin. Habitat A (opportunistic macroalgae, encrusting Porifera, bioeroders) characterizes reefs closest to the coastline, which are affected by coastal currents and river inputs. Habitat B is distinguished by massive Porifera, erect Tunicata, and non-calcareous encrusting algae (Peyssonnelia spp.). Habitat C (non articulated coralline, Polycitor adriaticus) is predicted in deeper areas. The onshore-offshore gradient explains the variability of the assemblages because of the influence of coastal freshwater, which is the main driver of nutrient dynamics. This model supports the interpretation of Habitat A and C as the extremes of a gradient that characterizes the epibenthic assemblages, while Habitat B demonstrates intermediate characteristics. Areas of transition are a natural feature of the marine environment and may include a mixture of habitats and species. The habitats proposed are easy to identify in the field, are related to different environmental features, and may be suitable for application in studies focused on other geographic areas. The habitat model outputs provide insight into the environmental drivers that control the distribution of the habitat and can be used to guide future research efforts and cost-effective management and conservation plans. PMID- 26560892 TI - Advantage of tacrolimus/mycophenolate mofetil regimen for cytotoxic T cell mediated defence and its inhibition by additive steroid administration in high risk liver transplant recipients. AB - Our previous work revealed that the recipients with the highest pre-existing numbers of CD8(+) effector T cells (TE ) [hyperparathyroidism (HPT)E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre-existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty-one HPTE recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow-up until post-operative day 2000. Regarding the immunological mechanism, in type 1 TE perforin and interferon (IFN)-gamma were generated through the self-renewal of CD8(+) central memory T cells (TCM ), but decreased in the early post-transplant period due to marked down-regulation of interleukin (IL)-12 receptor beta-1 of TCM. In type 2, the self-renewal TCM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL 12Rbeta1(+) TCM levels, and increased at the highest level around the pre transplant levels of IL-12Rbeta1(+) TCM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration. PMID- 26560894 TI - Von Willebrand disease in the emergency department. AB - BACKGROUND: The emergency department (ED) is often the first medical contact point for von Willebrand disease (VWD) patients experiencing acute conditions, notably bleeding. However, knowledge of VWD disease types and management options by ED providers is uncertain. AIM: To determine the scope of VWD bleeding and treatment in the ED. METHODS: We evaluated medical record data in an IRB-approved study from 922 notes accounting for 385 ER visits by 183 VWD patients from a single large institution's emergency department. RESULTS: Over half the ED visits were for an active or suspected bleed, the majority of which were associated with trauma, surgery, epistaxis, gastrointestinal bleeding or gynaecologic bleeding. By treatment, only 25% of all bleeds, including 77.8% of those with menorrhagia and 50.0% of those with epistaxis, received DDAVP or von Willebrand factor concentrate (VWF). The likelihood of receiving treatment was related to referral source, with the highest rates of treatment in patients referred by a haematologist. CONCLUSIONS: These data suggest more patient and physician education are needed in managing patients with VWD, preferably at the time of diagnosis, including confirmation of the diagnosis, response to DDAVP testing, indication for DDAVP testing and formulation of a plan for suspected or actual bleeding. PMID- 26560895 TI - Molecular Approach to Targeted Therapy for Multiple Sclerosis. AB - The development and evolution of targeted therapy to any disease require the identification of targets amenable to treatment of patients. Here the pathogenetic signalling systems involved in multiple sclerosis are scrutinised to locate nodes of deregulation and dysfunction in order to devise strategies of drug development for targeted intervention. Oliogoclonal bands (OCB) are isoelectric focusing profiles of immunoglobulins synthesised in the central nervous system. OCBs enable the diagnosis of multiple sclerosis with high sensitivity and specificity and are related to the course of the disease and progression. The OCB patterns can be linked with the expression of angiogenic molecular species. Angiogenic signalling which has also been implicated in demyelination provides the option of using angiogenesis inhibitors in disease control. The PI3K (phosphoinositide 3-kinase)/Akt axis has emerged with a key role in myelination with its demonstrable links with mTOR mediated transcription of downstream target genes. Inflammatory signals and innate and acquired immunity from the activation of NF-kappaB (nuclear factor kappaB) responsive genes are considered. NF-kappaB signalling could be implicated in myelination. The transcription factor STAT (signal transducers and activators of transcription) and the EBV (Epstein- Barr virus) transcription factor BZLF1 contributing significantly to the disease process are a major environmental factor linked to MS. EBV can activate TGF (transforming growth factor) and VEGF (vascular endothelial growth factor) signalling. EBV microRNAs are reviewed as signalling mediators of pathogenesis. Stem cell transplantation therapy has lately gained much credence, so the current status of mesenchymal and hematopoietic stem cell therapy is reviewed with emphasis on the differential expression immune-related genes and operation of signalling systems. PMID- 26560893 TI - Prognostic value of p16 expression in Epstein-Barr virus-positive nasopharyngeal carcinomas. AB - BACKGROUND: Overexpression of p16 is associated with improved outcomes among patients with oropharyngeal carcinoma. However, its role in the outcomes of patients with nasopharyngeal cancer (NPC) remains unclear. METHODS: Eighty-six patients with NPC treated at MD Anderson Cancer Center from 2000 to 2014 were identified. Epstein-Barr virus (EBV) and human papillomavirus (HPV) status were determined by in situ hybridization (ISH) and p16 by immunohistochemical staining. RESULTS: EBV positivity was associated with extended overall survival (OS; median, 95.0 vs 44.9 months; p < .004), progression-free survival (PFS; median, 80.4 vs 28.1 months; p < .013), and locoregional control (median, 104.4 vs 65.5 months; p < .043). In patients with EBV-positive tumors, p16 overexpression correlated with improved PFS (median, 106.3 vs 27.1 months; p < .02) and locoregional control (median, 93.6 vs 64.5 months; p < .02). CONCLUSION: P16 overexpression is associated with improved PFS and locoregional control in patients with EBV-positive NPC. P16 expression may complement EBV status in predicting treatment outcomes for patients with NPC. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1459-E1466, 2016. PMID- 26560896 TI - Indian Society of Gastroenterology. PMID- 26560898 TI - Asthma severity, not asthma control, is worse in atopic compared with nonatopic adolescents with asthma. AB - BACKGROUND: The effects of atopic and nonatopic asthma phenotypes on asthma morbidity are unclear. Moreover, asthma morbidity in patients without atopy might be mediated by immunoglobulin E (IgE). OBJECTIVE: To determine differences in morbidity in patients with asthma with and without atopy in a population of inner city adolescents with asthma and to assess the impact of total IgE (tIgE) in this population. METHODS: Data were obtained from 546 inner-city adolescents in the Asthma Control Evaluation study. A positive skin prick test reaction to 14 aeroallergens and specific IgE to 5 aeroallergens determined atopic status. High (>=75th percentile) and low (<=25th percentile) tIgE levels were categorized. Asthma control (Asthma Control Test) and asthma severity (Composite Asthma Severity Index [CASI]) were measured at multiple time points over 1 year. Fractional exhaled nitric oxide (FeNO) and measurements of morbidity also were collected. Multivariable and repeated measures analyses modeled the relation between atopic status and morbidity. RESULTS: Baseline CASI scores increased 0.90 point (P < .05) and FeNO increased 0.85 natural logarithmic unit (P < .001) in participants with vs without atopy. Repeated measures analyses showed consistent results. Participants without atopy and increased tIgE had FeNO 0.73 natural log unit higher (P < .01) than low tIgE and a nonsignificant increase in CASI. The CASI score and FeNO levels were higher for high than for low tIgE in participants with atopy. CONCLUSION: In this population, participants with atopic asthma had worse asthma severity and higher FeNO compared with those with nonatopic asthma, but no difference in control. In all participants, higher tIgE indicated worse severity and higher FeNO. In this population, asthma severity and FeNO might be mediated by IgE in the 2 asthma phenotypes. PMID- 26560897 TI - Membrane Topology and Biochemical Characterization of the Escherichia coli BacA Undecaprenyl-Pyrophosphate Phosphatase. AB - Several integral membrane proteins exhibiting undecaprenyl-pyrophosphate (C55-PP) phosphatase activity were previously identified in Escherichia coli that belonged to two distinct protein families: the BacA protein, which accounts for 75% of the C55-PP phosphatase activity detected in E. coli cell membranes, and three members of the PAP2 phosphatidic acid phosphatase family, namely PgpB, YbjG and LpxT. This dephosphorylation step is required to provide the C55-P carrier lipid which plays a central role in the biosynthesis of various cell wall polymers. We here report detailed investigations of the biochemical properties and membrane topology of the BacA protein. Optimal activity conditions were determined and a narrow-range substrate specificity with a clear preference for C55-PP was observed for this enzyme. Alignments of BacA protein sequences revealed two particularly well-conserved regions and several invariant residues whose role in enzyme activity was questioned by using a site-directed mutagenesis approach and complementary in vitro and in vivo activity assays. Three essential residues Glu21, Ser27, and Arg174 were identified, allowing us to propose a catalytic mechanism for this enzyme. The membrane topology of the BacA protein determined here experimentally did not validate previous program-based predicted models. It comprises seven transmembrane segments and contains in particular two large periplasmic loops carrying the highly-conserved active site residues. Our data thus provide evidence that all the different E. coli C55-PP phosphatases identified to date (BacA and PAP2) catalyze the dephosphorylation of C55-PP molecules on the same (outer) side of the plasma membrane. PMID- 26560899 TI - Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients. AB - BACKGROUND: Over-the-counter phenylephrine hydrochloride (PEH) is used for relief of nasal congestion caused by allergic rhinitis; however, data to support its efficacy are lacking. The US Food and Drug Administration recommended clinical trials to evaluate the efficacy and safety of PEH in patients with this condition. OBJECTIVE: To evaluate the efficacy and safety of PEH 30-mg modified release (MR) tablets in patients with nasal congestion caused by allergic rhinitis in a multicenter, randomized, double-blinded, placebo-controlled, 2-arm, parallel-group study. METHODS: Eligible adults at least 18 years old with documented hypersensitivity to fall pollen allergens were randomized to PEH-MR or placebo every 12 hours for 7 days from August 30 to October 12, 2011. The primary end point was mean change from baseline during the entire treatment period in daily reflective nasal congestion score. Secondary end points included changes in other symptom score assessments, time to maximal effect, duration of effect, and quality of life. Safety assessments included adverse events, serious adverse events, vital signs, physical examination, and electrocardiograms. RESULTS: Of 575 patients, 288 received PEH-MR and 287 received placebo. No significant beneficial difference was detected between PEH-MR and placebo for the primary end point (PEH-MR, mean -0.394, SD 0.4880; placebo, mean -0.412, SD 0.5383; P = .2655). Likewise, no significant differences were observed for most secondary end points or quality of life. Overall, 89 of 575 patients (15.5%), equally distributed between the PEH-MR and placebo groups, experienced at least 1 treatment-emergency adverse event. CONCLUSION: PEH-MR 30-mg tablets taken orally every 12 hours for 7 days is not more efficacious than placebo in relieving nasal congestion caused by allergic rhinitis. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT01413958, protocol CL2011-06. PMID- 26560900 TI - Essential echocardiographic evaluation in patients with suspected pulmonary hypertension: an overview for the practicing physician. AB - Prompt and accurate diagnosis of patients presenting with symptoms suggestive of pulmonary arterial hypertension (PAH) is of outmost importance as delays in identifying this clinical entity have detrimental effects on both morbidity and mortality. Initial noninvasive assessment of these patients has traditionally included a number of routine tests of which transthoracic echocardiography (TTE) has been shown to either confirm the presence of structural anomalies of the right ventricle (RV) indicative of PAH or exclude other potential causes of pulmonary hypertension (PH). Consequently, TTE has become a well-validated and readily available imaging tool not only used for this initial screening but also for routine follow-up of PH patients. Since chronic PH is known to unbalance the normal hemodynamic and mechanical homeostatic interaction between the RV and pulmonary circulation; the resulting response is that of an abnormal RV remodeling, clinically translated into progressive RV hypertrophy and dilatation. An enlarged and hypertrophied RV not only would eventually lose effective contractility but also this gradual decline in RV systolic function is the main abnormality in determining adverse clinical outcomes. Therefore, it is of outmost importance that TTE examination be comprehensive but most importantly accurate and reproducible. This review aims to highlight the most important objective measures that can be routinely employed, without added complexity, that will certainly enhance the interpretation and advance our understanding of the hemodynamic and mechanical abnormalities that PH exerts on the RV. PMID- 26560901 TI - Bowel Management and Quality of Life in Children With Spina Bifida in South Korea. AB - Bowel management is a concern in patients with spina bifida. We evaluated the status of bowel management in children with spina bifida (SB) and the effects on quality of life (QoL) of children and their caregivers. Data were collected from 173 children with SB between January and June 2011, whose bowel management status and QoL were assessed using a self-administered questionnaire. Of the 173 children, 38 (22.0%) reported normal defecation, 73 (42.2%) reported constipation only, and 62 (35.8%) reported fecal incontinence with/without constipation. For defecation, 59 children (34.1%) used digital stimulation or manual extraction, 28 (16.2%) used suppositories or enemas, 35 (20.3%) used laxatives, 4 (2.3%) used an antegrade continence enema, and 3 (1.7%) used transanal irrigation. There were significant differences in QoL, depending on defecation symptoms. Children with fecal incontinence and their caregivers had difficulties in travel and socialization (p < .0001), caregivers' emotions (p < .0001), family relationships (p < .0001), and finances (p < .0001). Constipation and fecal incontinence affect QoL of children with SB and their caregivers. Therefore, more attention should be paid to bowel problems and help should be provided to children and their caregivers to improve QoL. PMID- 26560902 TI - Role of band 3 in the erythrocyte membrane structural changes under thermal fluctuations -multi scale modeling considerations. AB - An attempt was made to discuss and connect various modeling approaches on various time and space scales which have been proposed in the literature in order to shed further light on the erythrocyte membrane rearrangement caused by the cortex lipid bilayer coupling under thermal fluctuations. Roles of the main membrane constituents: (1) the actin-spectrin cortex, (2) the lipid bilayer, and (3) the trans membrane protein band 3 and their course-consequence relations were considered in the context of the cortex non linear stiffening and corresponding anomalous nature of energy dissipation. The fluctuations induce alternating expansion and compression of the membrane parts in order to ensure surface and volume conservation. The membrane structural changes were considered within two time regimes. The results indicate that the cortex non linear stiffening and corresponding anomalous nature of energy dissipation are related to the spectrin flexibility distribution and the rate of its changes. The spectrin flexibility varies from purely flexible to semi flexible. It is influenced by: (1) the number of band 3 molecules attached to single spectrin filaments, and (2) phosphorylation of the actin-junctions. The rate of spectrin flexibility changes depends on the band 3 molecules rearrangement. PMID- 26560903 TI - Expression of Vascular Endothelial Growth Factor by Retinal Pigment Epithelial Cells Induced by Amyloid-beta Is Depressed by an Endoplasmic Reticulum Stress Inhibitor. AB - PURPOSE: Amyloid-beta (Abeta) is a 36- to 43-amino-acid peptide that is a constituent of drusen, and it has been demonstrated to upregulate vascular endothelial growth factor (VEGF) expression by retinal pigment epithelial (RPE) cells. This study aimed to determine whether 4-phenylbutyl phosphonylacetate (PBA), a known endoplasmic reticulum (ER) stress inhibitor, can reduce Abeta induced expression of VEGF in RPE cells. METHODS: Abeta was added to the medium of regularly cultured or polarized ARPE-19 cells, a human RPE cell line, with or without PBA. The levels of VEGF and ER stress markers, namely GRP78/Bip, cleaved caspases 4 and 12 and GADD153/C-EBP homologous protein, were determined by enzyme linked immunoassay, immunocytochemistry and Western blotting. RESULTS: Exposure of ARPE-19 cells to Abeta induced GRP78/Bip expression and activated caspases 4 and 12; however, their expression was decreased by simultaneous exposure to PBA. Abeta increased the expression of VEGF both in regularly cultured and polarized ARPE-19 cells, but it was suppressed by PBA. PBA did not cause RPE cell apoptosis. CONCLUSION: Abeta has been suggested to be involved in the development of age-related macular degeneration; therefore, our findings suggest that drugs that target ER stress should be considered for the treatment of age-related macular degeneration. PMID- 26560904 TI - Modal wavefront reconstruction from slope measurements for rectangular apertures. AB - We present a modal wavefront reconstruction from slope measurements for rectangular optical components of high-power laser systems. Wavefront reconstruction with slope data is an important approach used for wavefront control or correction in high-power systems. In this work, we derive a complete set of orthonormal wavefront slope polynomials for rectangular apertures and describe the modal method for obtaining wavefront representation with the aberration balancing property. Error propagation properties for the modal method are evaluated and compared with the Southwell method. The cross-coupling error is also discussed. Numerical experiments are conducted to illustrate that the modal method can achieve a higher accuracy than the Southwell method. In addition, we also investigate the influence of noise on the modal method compared with that of the Southwell method. PMID- 26560905 TI - Sparsity-assisted solution to the twin image problem in phase retrieval. AB - The problem of iterative phase retrieval from Fourier transform magnitude data for complex-valued objects is known to suffer from the twin image problem. In particular, when the object support is centrosymmetric, the iterative solution often stagnates such that the resultant complex image contains the features of both the desired solution and its inverted and complex-conjugated replica. In this work we make an important observation that the ideal solution without the twin image is typically more sparse in some suitable transform domain as compared to the stagnated solution. We further show that introducing a sparsity-enhancing step in the iterative algorithm can address the twin image problem without the need to change the object support throughout the iterative process even when the object support is centrosymmetric. In a simulation study, we use binary and gray scale pure phase objects and illustrate the effectiveness of the sparsity assisted phase recovery in the context of the twin image problem. PMID- 26560906 TI - Reconstruction algorithm for fluorescence molecular tomography using sorted L-one penalized estimation. AB - Fluorescence molecular tomography (FMT) has been a promising imaging tool that provides convenience for accurate localization and quantitative analysis of the fluorescent probe. In this study, we present a reconstruction method combining sorted L-one penalized estimation with an iterative-shrinking permissible region strategy to reconstruct fluorescence targets. Both numerical simulation experiments on a three-dimensional digital mouse model and physical experiments on a cubic phantom were carried out to validate the accuracy, effectiveness, and robustness of the proposed method. The results indicate that the proposed method can produce better location and satisfactory fluorescent yield with computational efficiency, which makes it a practical and promising reconstruction method for FMT. PMID- 26560907 TI - Nonuniqueness of optical theorem detectors. AB - We demonstrate and discuss the multitude of ways in which the extinct power of a scatterer can be measured. To tie some of the developed results to the classical statement of the optical theorem involving the imaginary part of the forward scattering amplitude, particular attention is given to plane wave excitation. On the other hand, the general results apply to more general probing fields including near fields carrying evanescent components. Novel optical theorem detectors are derived that are based on the Kirchhoff-Helmholtz and Rayleigh Sommerfeld-based formulations of diffraction, backpropagation, and boundary-value problems as well as on the canonical multipole expansion. The derived detectors also lead to novel expressions for the extinct power in terms of the incident and scattered fields. Applications of the derived results to scattering power sensing with near-field data are also discussed. PMID- 26560908 TI - Optimal beam focusing through turbulence. AB - Beam spread and beam wandering are the most perceptible effects of atmospheric turbulence on propagating laser beams. The width of the mean irradiance profile is typically used to characterize the beam spread. This so-called long-term (LT) statistic allows for a relatively simple theoretical description. However, the LT beam size is not a very practical measure of the beam spread because its measurements are sensitive to the movements of the source and detector, and to the large-scale variations of the refractive index that are not associated with turbulence. The short-term (ST) beam spread is measured relative to the instantaneous position of the beam center and is free of these drawbacks, but has not been studied as thoroughly as the LT spread. We present a theoretical model for the ST beam irradiance that is based on the parabolic equation for the beam wave propagation in random media, and the Markov approximation for calculation of the statistics of the optical field, and discuss an approximation that allows introduction of the isoplanatic ST point spread function (PSF). Unlike the LT PSF, the ST PSF depends on the overall beam geometry. This allows optimization of the initial beam field in terms of minimizing the ST beam size at the observation plane. Calculations supporting this conjecture are presented for the simple case of the coherent Gaussian beam, and Kolmogorov turbulence. PMID- 26560909 TI - Unified beam splitter of fused silica grating under the second Bragg incidence. AB - A unified design for a 1*2 beam splitter of dielectric rectangular transmission gratings under the second Bragg incidence is theoretically investigated for TE- and TM-polarized light. The empirical equations of the relative grating parameters (ratio of the absolute one to incidence wavelength) for this design are also obtained with the simplified modal method (SMM). The influences of polarization of incident light and relative grating parameters on the performance of the beam splitter are thoroughly studied based on the SMM and rigorous coupled wave analysis. Two specific gratings are demonstrated with an even split and high diffraction efficiency (>94% for TE polarization and >97% for the TM counterpart). The unified profiles of the 1*2 beam splitter are independent from the incidence wavelength since the refractive index of fused silica is roughly a constant over a wide range of wavelengths, which should be promising for future applications. PMID- 26560910 TI - Free-form lens for rectangular illumination with the target plane rotating at a certain angle. AB - We have proposed a method for rectangular illumination in a (u, v) coordinate system with high collection efficiency and favorable uniformity. In our proposed approach, with the target plane rotating at a certain angle around the z axis, one of the diagonals on the rectangular target plane moves to the coordinate axis; then, we partition the light source and target plane into grids. The intersection points of the grids are in one-to-one correspondence from the source to the target plane. This improved method will avoid the one-to-many correspondence topological relationship in the traditional (u, v) mapping method; uniformity of the illuminance pattern will be promoted. Based on this method, lenses are designed for rectangular target plane illumination; uniformity over 0.83 and efficiency of about 0.92 are obtained with a 1 mm*1 mm LED Lambertian source. PMID- 26560911 TI - Stitching interferometry of high numerical aperture cylindrical optics without using a fringe-nulling routine. AB - Stitching interferometry is a common method for measuring the figure error of high numerical aperture optics. However, subaperture measurement usually requires a fringe-nulling routine, thus making the stitching procedure complex and time consuming. The challenge when measuring a surface without a fringe-nulling routine is that the rays no longer perpendicularly hit the surface. This violation of the null-test condition can lead to high fringe density and introduce high-order misalignment aberrations into the measurement result. This paper demonstrates that the high-order misalignment aberrations can be characterized by low-order misalignment aberrations; then, an efficient method is proposed to separate the high-order misalignment aberrations from subaperture data. With the proposed method, the fringe-nulling routine is not required. Instead, the subaperture data is measured under a nonzero fringe pattern. Then, all possible misalignment aberrations are removed with the proposed method. Finally, the full aperture map is acquired by connecting all subaperture data together. Experimental results showing the feasibility of the proposed procedure are presented. PMID- 26560912 TI - High-order modes in cavity-resonator-integrated guided-mode resonance filters (CRIGFs). AB - Cavity-resonator-integrated guided-mode resonance filters (CRIGFs) are optical filters based on weak coupling by a grating between a free-space propagating optical mode and a guided mode, like guided-mode resonance filters (GMRFs). As compared to GMRFs they offer narrowband reflection with small aperture and high angular acceptance. We report experimental characterization and theoretical modeling of unexpected high-order reflected modes in such devices. Using coupled mode modeling and moire analysis we provide physical insight on key mechanisms ruling CRIGF properties. This model could serve as a simple and efficient framework to design new reflectors with tailored spatial and spectral modal reflectivities. PMID- 26560913 TI - Analyzing the propagation behavior of scintillation index and bit error rate of a partially coherent flat-topped laser beam in oceanic turbulence. AB - In this paper, on the basis of the extended Huygens-Fresnel principle, a semianalytical expression for describing on-axis scintillation index of a partially coherent flat-topped (PCFT) laser beam of weak to moderate oceanic turbulence is derived; consequently, by using the log-normal intensity probability density function, the bit error rate (BER) is evaluated. The effects of source factors (such as wavelength, order of flatness, and beam width) and turbulent ocean parameters (such as Kolmogorov microscale, relative strengths of temperature and salinity fluctuations, rate of dissipation of the mean squared temperature, and rate of dissipation of the turbulent kinetic energy per unit mass of fluid) on propagation behavior of scintillation index, and, hence, on BER, are studied in detail. Results indicate that, in comparison with a Gaussian beam, a PCFT laser beam with a higher order of flatness is found to have lower scintillations. In addition, the scintillation index and BER are most affected when salinity fluctuations in the ocean dominate temperature fluctuations. PMID- 26560914 TI - Fast reconstruction of fluorophore concentration variation based on the derivation of the diffusion equation. AB - The information of fluorophore concentration variation (FCV) has the potential for drug development and tumor studies, but the reconstruction of FCV is time consuming in dynamic fluorescence molecular tomography (DFMT). In this paper, a time-efficient reconstruction method for FCV is presented. The system equation of this method is derived from the derivation of the diffusion equation, and its size does not change with the number of frames. The computational time can be significantly reduced by using this method because the images of different frames are reconstructed separately. Simulations and phantom experiments are performed to validate the performance of the proposed method. The results show that compared with the previous method, the proposed method can obtain better results and consumes less computational time with the same number of iterations. In addition, the time consumption in a single iteration of the proposed method increases much slower with the number of frames. PMID- 26560915 TI - Spatial-frequency-based metric for image superresolution. AB - The image processing technique known as superresolution (SR) has the potential to allow engineers to specify lower resolution and, therefore, less expensive cameras for a given task by enhancing the base camera's resolution. This is especially true in the remote detection and classification of objects in the environment, such as aircraft or human faces. Performing each of these tasks requires a minimum image "sharpness" which is quantified by a maximum resolvable spatial frequency, which is, in turn, a function of the camera optics, pixel sampling density, and signal-to-noise ratio. Much of the existing SR literature focuses on SR performance metrics for candidate algorithms, such as perceived image quality or peak SNR. These metrics can be misleading because they also credit deblurring and/or denoising in addition to true SR. In this paper, we propose a new, task-based metric where the performance of an SR algorithm is, instead, directly tied to the probability of successfully detecting critical spatial frequencies within the scene. PMID- 26560916 TI - Computational photography with plenoptic camera and light field capture: tutorial. AB - Photography is a cornerstone of imaging. Ever since cameras became consumer products more than a century ago, we have witnessed great technological progress in optics and recording mediums, with digital sensors replacing photographic films in most instances. The latest revolution is computational photography, which seeks to make image reconstruction computation an integral part of the image formation process; in this way, there can be new capabilities or better performance in the overall imaging system. A leading effort in this area is called the plenoptic camera, which aims at capturing the light field of an object; proper reconstruction algorithms can then adjust the focus after the image capture. In this tutorial paper, we first illustrate the concept of plenoptic function and light field from the perspective of geometric optics. This is followed by a discussion on early attempts and recent advances in the construction of the plenoptic camera. We will then describe the imaging model and computational algorithms that can reconstruct images at different focus points, using mathematical tools from ray optics and Fourier optics. Last, but not least, we will consider the trade-off in spatial resolution and highlight some research work to increase the spatial resolution of the resulting images. PMID- 26560917 TI - Iterative color constancy with temporal filtering for an image sequence with no relative motion between the camera and the scene. AB - Color constancy is the ability to perceive the color of a surface as invariant even under changing illumination. In outdoor applications, such as mobile robot navigation or surveillance, the lack of this ability harms the segmentation, tracking, and object recognition tasks. The main approaches for color constancy are generally targeted to static images and intend to estimate the scene illuminant color from the images. We present an iterative color constancy method with temporal filtering applied to image sequences in which reference colors are estimated from previous corrected images. Furthermore, two strategies to sample colors from the images are tested. The proposed method has been tested using image sequences with no relative movement between the scene and the camera. It also has been compared with known color constancy algorithms such as gray-world, max-RGB, and gray-edge. In most cases, the iterative color constancy method achieved better results than the other approaches. PMID- 26560918 TI - Influence of imaging resolution on color fidelity in digital archiving. AB - Color fidelity is of paramount importance in digital archiving. In this paper, the relationship between color fidelity and imaging resolution was explored by calculating the color difference of an IT8.7/2 color chart with a CIELAB color difference formula for scanning and simulation images. Microscopic spatial sampling was used in selecting the image pixels for the calculations to highlight the loss of color information. A ratio, called the relative imaging definition (RID), was defined to express the correlation between image resolution and color fidelity. The results show that in order for color differences to remain unrecognizable, the imaging resolution should be at least 10 times higher than the physical dimension of the smallest feature in the object being studied. PMID- 26560919 TI - Measurement of transmission and reflection from a thick anisotropic crystal modeled by a sum of incoherent partial waves. AB - Formulas for modeling ellipsometric measurements of bianisotropic crystals assume perfectly coherent plane wave illumination. As such, the finite coherence of typical spectroscopic ellipsometers renders such formulas invalid for crystals thicker than a few micrometers. Reflection measurements of thick crystalline slabs show depolarization. Researchers have proposed strategies for the full accounting for multiply reflected incoherent waves in anisotropic, arbitrarily oriented crystals [Appl. Opt.41, 2521 (2002).APOPAI0003 693510.1364/AO.41.002521], but to the best of our knowledge these methods have not been tested by explicit measurements. It is shown that by a summation of multiply reflected incoherent waves, transmission and reflection measurements of thick quartz slabs can be interpreted in terms of the constitutive material parameters. PMID- 26560920 TI - Generation and propagation of an electromagnetic Gaussian Schell-model vortex beam. AB - We outline the propagation of an electromagnetic Gaussian Schell-model (EGSM) vortex beam through a paraxial ABCD optical system and analyze the vortex phase induced changes of the statistical properties, such as average intensity, state of polarization, and degree of polarization (DOP), of a focused EGSM beam. It is found that one can shape the beam profile of an EGSM vortex beam in the focal plane through varying its initial topological charge, DOP, and coherence widths. Furthermore, we first report experimental generation of an EGSM vortex beam and measure its focusing properties in experiments. Our experimental results are consistent with the numerical results and may be useful in material thermal processing and particle trapping. PMID- 26560921 TI - Long-distance Bessel beam propagation through Kolmogorov turbulence. AB - Free-space optical communication has the potential to transmit information with both high speed and security. However, since it is unguided it suffers from losses due to atmospheric turbulence and diffraction. To overcome the diffraction limits the long-distance propagation of Bessel beams is considered and compared against Gaussian beam properties. Bessel beams are shown to have a number of benefits over Gaussian beams when propagating through atmospheric turbulence. PMID- 26560922 TI - Rapid calculation of paraxial wave propagation for cylindrically symmetric optics. AB - When calculating the focusing properties of cylindrically symmetric focusing optics, numerical wave propagation calculations can be carried out using the quasi-discrete Hankel transform (QDHT). We describe here an implementation of the QDHT where a partial transform matrix can be stored to speed up repeated wave propagations over specified distances, with reduced computational memory requirements. The accuracy of the approach is then verified by comparison with analytical results, over propagation distances with both small and large Fresnel numbers. We then demonstrate the utility of this approach for calculating the focusing properties of Fresnel zone plate optics that are commonly used for x-ray imaging applications and point to future applications of this approach. PMID- 26560923 TI - Comparative analysis of imaging configurations and objectives for Fourier microscopy. AB - Fourier microscopy is becoming an increasingly important tool for the analysis of optical nanostructures and quantum emitters. However, achieving quantitative Fourier space measurements requires a thorough understanding of the impact of aberrations introduced by optical microscopes that have been optimized for conventional real-space imaging. Here we present a detailed framework for analyzing the performance of microscope objectives for several common Fourier imaging configurations. To this end, we model objectives from Nikon, Olympus, and Zeiss using parameters that were inferred from patent literature and confirmed, where possible, by physical disassembly. We then examine the aberrations most relevant to Fourier microscopy, including the alignment tolerances of apodization factors for different objective classes, the effect of magnification on the modulation transfer function, and vignetting-induced reductions of the effective numerical aperture for wide-field measurements. Based on this analysis, we identify an optimal objective class and imaging configuration for Fourier microscopy. In addition, the Zemax files for the objectives and setups used in this analysis have been made publicly available as a resource for future studies. PMID- 26560924 TI - Color-weak compensation using local affine isometry based on discrimination threshold matching. AB - We develop algorithms for color-weak compensation and color-weak simulation based on Riemannian geometry models of color spaces. The objective function introduced measures the match of color discrimination thresholds of average normal observers and a color-weak observer. The developed matching process makes use of local affine maps between color spaces of color-normal and color-weak observers. The method can be used to generate displays of images that provide color-normal and color-weak observers with a similar color difference experience. It can also be used to simulate the perception of a color-weak observer for color-normal observers. We also introduce a new database of measurements of color discrimination threshold data for color-normal and color-weak observers obtained at different lightness levels in CIELUV space. The compensation methods include compensations of chromaticity using local affine maps between chromaticity planes of color-normal and color-weak observers, and one-dimensional (1D) compensation on lightness. We describe how to determine correspondences between the origins of local coordinates in color spaces of color-normal and color-weak observers using a neighborhood expansion method. After matching the origins of the two coordinate systems, a local affine map is estimated by solving a nonlinear equation, or singular-value-decomposition (SVD). We apply the methods to natural images and evaluate their performance using the semantic differential (SD) method. PMID- 26560925 TI - Propagation properties of right-hand circularly polarized Airy-Gaussian beams through slabs of right-handed materials and left-handed materials. AB - The propagation of right-hand circularly polarized Airy-Gaussian beams (RHCPAiGBs) through slabs of right-handed materials (RHMs) and left-handed materials (LHMs) is investigated analytically and numerically with the transfer matrix method. An approximate analytical expression for the RHCPAiGBs passing through a paraxial ABCD optical system is derived on the basis of the Huygens diffraction integral formula. The intensity and the phase distributions of the RHCPAiGBs through RHMs and LHMs are demonstrated. The influence of the parameter chi0 on the propagation of RHCPAiGBs through RHM and LHM slabs is investigated. The RHCPAiGBs possess transverse-momentum currents, which shows that the physics underlying this intriguing accelerating effect is that of the combined contributions of the transverse spin and transverse orbital currents. Additionally, we go a step further to explore the radiation force including the gradient force and scattering force of the RHCPAiGBs. PMID- 26560926 TI - Uniform refraction in negative refractive index materials. AB - We study the problem of constructing an optical surface separating two homogeneous, isotropic media, one of which has a negative refractive index. In doing so, we develop a vector form of Snell's law, which is used to study surfaces possessing a certain uniform refraction property, in both the near- and far-field cases. In the near-field problem, unlike the case when both materials have positive refractive indices, we show that the resulting surfaces can be neither convex nor concave. PMID- 26560927 TI - High-resolution 3D phase imaging using a partitioned detection aperture: a wave optic analysis. AB - Quantitative phase imaging has become a topic of considerable interest in the microscopy community. We have recently described one such technique based on the use of a partitioned detection aperture, which can be operated in a single shot with an extended source [Opt. Lett.37, 4062 (2012)OPLEDP0146 959210.1364/OL.37.004062]. We follow up on this work by providing a rigorous theory of our technique using paraxial wave optics, where we derive fully 3D spread functions for both phase and intensity. Using these functions, we discuss methods of phase reconstruction for in- and out-of-focus samples, insensitive to weak attenuations of light. Our approach provides a strategy for detection limited lateral resolution with an extended depth of field and is applicable to imaging smooth and rough samples. PMID- 26560928 TI - Smart light random memory sprays Retinex: a fast Retinex implementation for high quality brightness adjustment and color correction. AB - Removing the influence of illumination on image colors and adjusting the brightness across the scene are important image enhancement problems. This is achieved by applying adequate color constancy and brightness adjustment methods. One of the earliest models to deal with both of these problems was the Retinex theory. Some of the Retinex implementations tend to give high-quality results by performing local operations, but they are computationally relatively slow. One of the recent Retinex implementations is light random sprays Retinex (LRSR). In this paper, a new method is proposed for brightness adjustment and color correction that overcomes the main disadvantages of LRSR. There are three main contributions of this paper. First, a concept of memory sprays is proposed to reduce the number of LRSR's per-pixel operations to a constant regardless of the parameter values, thereby enabling a fast Retinex-based local image enhancement. Second, an effective remapping of image intensities is proposed that results in significantly higher quality. Third, the problem of LRSR's halo effect is significantly reduced by using an alternative illumination processing method. The proposed method enables a fast Retinex-based image enhancement by processing Retinex paths in a constant number of steps regardless of the path size. Due to the halo effect removal and remapping of the resulting intensities, the method outperforms many of the well-known image enhancement methods in terms of resulting image quality. The results are presented and discussed. It is shown that the proposed method outperforms most of the tested methods in terms of image brightness adjustment, color correction, and computational speed. PMID- 26560929 TI - Non-dyadic fisheye lens correction model for image enhancement. AB - This paper presents a non-dyadic framework to improve example-based enhancement of radially distorted images acquired by a very wide-angle lens. In order to remove both jagging and blurring artifacts in the correction process of the fisheye lens' barrel distortion, the proposed method first performs non-dyadic or multiple-step geometric correction based on the parabolic equation-based lens distortion model. At each correction step, an example-based image enhancement method removes undesired geometric correction artifacts such as jagging and blurring. Experimental results demonstrate that the proposed method outperforms existing fisheye lens image enhancement methods in the sense of both subjective and objective measures. Based on both theoretical advancement and experimental results, the proposed method can be used for various wide-view imaging applications including vehicle front- and rear-view cameras and wide-angle video surveillance systems. PMID- 26560930 TI - Plane wave analysis of coherent holographic image reconstruction by phase transfer (CHIRPT). AB - Fluorescent imaging plays a critical role in a myriad of scientific endeavors, particularly in the biological sciences. Three-dimensional imaging of fluorescent intensity often requires serial data acquisition, that is, voxel-by-voxel collection of fluorescent light emitted throughout the specimen with a nonimaging single-element detector. While nonimaging fluorescence detection offers some measure of scattering robustness, the rate at which dynamic specimens can be imaged is severely limited. Other fluorescent imaging techniques utilize imaging detection to enhance collection rates. A notable example is light-sheet fluorescence microscopy, also known as selective-plane illumination microscopy, which illuminates a large region within the specimen and collects emitted fluorescent light at an angle either perpendicular or oblique to the illumination light sheet. Unfortunately, scattering of the emitted fluorescent light can cause blurring of the collected images in highly turbid biological media. We recently introduced an imaging technique called coherent holographic image reconstruction by phase transfer (CHIRPT) that combines light-sheet-like illumination with nonimaging fluorescent light detection. By combining the speed of light-sheet illumination with the scattering robustness of nonimaging detection, CHIRPT is poised to have a dramatic impact on biological imaging, particularly for in vivo preparations. Here we present the mathematical formalism for CHIRPT imaging under spatially coherent illumination and present experimental data that verifies the theoretical model. PMID- 26560931 TI - Fourier optics analysis of phase-mask-based path-length-multiplexed optical coherence tomography. AB - Optical coherence tomography (OCT) is an imaging technique that constructs a depth-resolved image by measuring the optical path-length difference between broadband light backscattered from a sample and a reference surface. For many OCT sample arm optical configurations, sample illumination and backscattered light detection share a common path. When a phase mask is placed in the sample path, features in the detected signal are observed, which suggests that an analysis of a generic common path OCT imaging system is warranted. In this study, we present a Fourier optics analysis using a Fresnel diffraction approximation of an OCT system with a path-length-multiplexing element (PME) inserted in the sample arm optics. The analysis may be generalized for most phase-mask-based OCT systems. A radial-angle-diverse PME is analyzed in detail, and the point spread function, coherent transfer function, sensitivity of backscattering angular diversity detection, and signal formation in terms of sample spatial frequency are simulated and discussed. The analysis reveals important imaging features and application limitations of OCT imaging systems with a phase mask in the sample path optics. PMID- 26560932 TI - Compressive spectral polarization imaging by a pixelized polarizer and colored patterned detector. AB - A compressive spectral and polarization imager based on a pixelized polarizer and colored patterned detector is presented. The proposed imager captures several dispersed compressive projections with spectral and polarization coding. Stokes parameter images at several wavelengths are reconstructed directly from 2D projections. Employing a pixelized polarizer and colored patterned detector enables compressive sensing over spatial, spectral, and polarization domains, reducing the total number of measurements. Compressive sensing codes are specially designed to enhance the peak signal-to-noise ratio in the reconstructed images. Experiments validate the architecture and reconstruction algorithms. PMID- 26560933 TI - Slot plasmonic waveguide based on doped-GaAs for terahertz deep-subwavelength applications. AB - A new plasmonic waveguide for deep-subwavelength field localization at the terahertz (THz) range of frequency is proposed. GaAs with optimum doping level is used as the plasmonic material. The waveguide structure is a narrow slot in a thin GaAs film on top of the quartz substrate. The waveguide characteristics are analyzed, and its dimensions are optimized to minimize the losses. It is shown that the mode size of the proposed waveguide is less than lambda/16 by lambda/16. The proposed plasmonic waveguide can be a platform for numerous THz plasmonic based integrated devices, such as integrated sensors and imagers. PMID- 26560934 TI - Temperature variance dissipation equation and its relevance for optical turbulence modeling. AB - The 3D spectrum Phi(kappa) of the turbulent air temperature fluctuations is a key quantity for the physics of optical propagation through the turbulent atmosphere. The standard model, which was derived in the 1950s by Tatarskii from the Obukhov Corrsin theory of homogeneous and isotropic turbulence, is Phi(kappa)=0.033CT2kappa(-11/3)h(kappal(0)), where kappa=|kappa| is the wavenumber, CT2 is the temperature structure parameter, l(0) is the inner temperature scale, and h(kappal(0) is a universal function that approaches 1 for wavenumbers in the inertial range and drops to zero for kappal(0)?1. Certain performance characteristics of optical systems, such as the scintillation index for small receiving apertures, depend sensitively on the functional form of h(y) at y~1. During the last 70 years, the optical-turbulence community has developed and applied various heuristic h(y) models. There is a constraint that any valid h(y) model has to fulfill: ?0infinityh(y)y(1/3)dy=(27/10)Gamma(1/3)=7.233. This constraint is a dimensionless form of the spectral temperature variance dissipation equation, which follows directly from first-principle fluid mechanics. We show that Tatarskii's cutoff (1961) and Gaussian (1971) models fulfill this constraint, while three more recent models, including the widely used Andrews model [J. Mod. Opt.39, 1849 (1992)JMOPEW0950 034010.1080/09500349214551931], do not. The dissipation constraint can be used to "recalibrate" the coefficients in these models. PMID- 26560935 TI - Intrinsic parameter determination of a paracatadioptric camera by the intersection of two sphere projections. AB - In this paper, a linear calibration method is proposed for a paracatadioptric camera using the images of two spheres. Two spheres are selected in space, and the two groups of their projection circles on the unit viewing sphere are made to intersect at four points. The quadrilateral consisting of four points is a rectangle, so a group of orthogonal directions can be determined in space to obtain a group of orthogonal vanishing points in the paracatadioptric image plane. Because of the relationship between orthogonal vanishing points and intrinsic camera parameters, the intrinsic parameters of a paracatadioptric camera can be linearly solved by at least five views satisfying the above conditions. First, one estimates the sphere images and their antipodal sphere images. Second, by solving the intersection of the images of two spheres and the intersection of the images of their antipodal spheres, a group of orthogonal vanishing points can be obtained in the image plane. Finally, by taking the relationship between the orthogonal vanishing points and the intrinsic camera parameters as constraint conditions, the intrinsic parameters of the paracatadioptric camera can be obtained. Simulation results and real image data demonstrate the effectiveness of our new algorithms. PMID- 26560936 TI - Determining the size and refractive index of microspheres using the mode assignments from Mie resonances. AB - A new method for determining the radius and refractive index of microspheres using Mie resonances is presented. Previous methods have relied on searching multidimensional space to find the radius and refractive index that minimize the difference between observed and calculated Mie resonances. For anything but simple refractive index functions, this process can be very time consuming. Here, we demonstrate that once the mode assignment for the observed Mie resonances is known, no search is necessary, and the radius and refractive index of best-fit can be found immediately. This superior and faster way to characterize microspheres using Mie resonances should supplant previous fitting algorithms. The derivation and implementation of the equations that give the parameters of best-fit are shown and discussed. Testing is performed on systems of physical interest, and the effect of noise on measured peak positions is investigated. PMID- 26560937 TI - Multi-resolution subspace-based optimization method for solving three-dimensional inverse scattering problems. AB - An innovative methodology is proposed to solve quantitative three-dimensional microwave imaging problems formulated within the contrast source framework. The introduced technique is based on the combination of an efficient iterative multiscaling strategy aimed at mitigating local minimum issue arising in inverse scattering problems, and a local search algorithm based on the subspace-based optimization method (SOM) devoted to effectively retrieving both the "deterministic" and the "ambiguous" parts of the unknown contrast currents. To achieve this goal, a nested iteration process is adopted in which the outer loop iteratively refines the region of interest (ROI) where the scatterers are detected, while the inner loop retrieves the dielectric properties of the scatterers within the ROIs. Selected numerical examples are also given to show the validity and robustness of the proposed algorithm in comparison with state-of the-art techniques. PMID- 26560938 TI - Designing illumination lenses and mirrors by the numerical solution of Monge Ampere equations. AB - We consider the inverse refractor and the inverse reflector problem. The task is to design a free-form lens or a free-form mirror that, when illuminated by a point light source, produces a given illumination pattern on a target. Both problems can be modeled by strongly nonlinear second-order partial differential equations of Monge-Ampere type. In [Math. Models Methods Appl. Sci.25, 803 (2015)MMMSEU0218-202510.1142/S0218202515500190], the authors have proposed a B spline collocation method, which has been applied to the inverse reflector problem. Now this approach is extended to the inverse refractor problem. We explain in depth the collocation method and how to handle boundary conditions and constraints. The paper concludes with numerical results of refracting and reflecting optical surfaces and their verification via ray tracing. PMID- 26560939 TI - Region-based active contours with cosine fitting energy for image segmentation. AB - In this paper, by employing the cosine function to express the so-called data fitting term in traditional active contour models, we propose an active contour model with the global cosine fitting energy for segmenting synthetic and real world images. After that, in order to segment the image with intensity inhomogeneity, we extend the proposed global model to the local cosine fitting energy. In addition, we introduce level set regularization terms into the proposed models to avoid the expensive computational cost which is usually caused by the reinitialization of the evolving level set function. Experimental results indicate that the proposed models are accurate and effective when applied to segment different types of images. Moreover, our models are more efficient and robust for segmenting the images with strong noise and clutter than the Chan-Vese model and the local binary fitting model. PMID- 26560940 TI - Lessons from black pepper: piperine and derivatives thereof. AB - INTRODUCTION: Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine like derivatives have shown an interesting range of pharmacological activities. In this context, significant advances have been made in the discovery of new chemical entities based on the piperine scaffold endowed with therapeutic potential. AREAS COVERED: The aim of this review is to provide a thorough inquiry on the therapeutic potential of piperine and related derivatives. It provides an overview of recent developments in patented processes and applications thereof between 2000 and 2015. EXPERT OPINION: Cumulative evidence shows that piperine is currently paving its way to become a privileged scaffold for the development of bioactive compounds with therapeutic application in multiple human diseases. In particular, piperine derivatives were shown to modulate the activity of several targets related to neurological disorders, including epilepsy, Parkinson's disease, depression and pain related disorders. Moreover, the efflux pump inhibitory ability of piperine and its analogues tackles important drug resistance mechanisms and may improve the clinical efficacy of antibiotic and anticancer drugs. Although the use of piperine as a scaffold for bioactive compounds is still in its early stages, the continuous exploration of this structure may lead to remarkable advances in drug discovery programs. PMID- 26560941 TI - Cancellation of the zeroth order by a low-contrast grating. AB - The cancellation of the 0th order is described by a low-contrast fused-silica grating. In reported works, the high-contrast grating and complicated structure were applied with reasonable and excellent performance. However, the low-contrast grating is proved that it can also cancel the 0th order with the period more than 2lambda in this paper. Grating parameters are optimized by using rigorous coupled wave analysis, whose physical essence for cancellation of the 0th order can be well explained by modal method. The fabrication tolerance is investigated for production of the low-contrast grating for cancellation of the 0th order, which can be potentially used for writing the fiber Bragg grating. PMID- 26560943 TI - Internet video chat (Skype) family conversations as a treatment of agitation in nursing home residents with dementia. PMID- 26560942 TI - Menin localization in cell membrane compartment. AB - Menin is encoded by the MEN1 gene, which is mutated in an inherited human syndrome, multiple endocrine neoplasia type 1(MEN1). Menin is primarily nuclear protein, acting as a tumor suppressor in endocrine organs, but as an oncogenic factor in the mixed lineage leukemia, in a tissue-specific manner. Recently, the crystal structures of menin with different binding partners reveal menin as a key scaffold protein that functionally interacts with various partners to regulate gene transcription in the nucleus. However, outside the nucleus, menin also regulates multiple signaling pathways that traverse the cell surface membrane. The precise nature regarding to how menin associates with the membrane fraction is poorly understood. Here we show that a small fraction of menin associates with the cell membrane fraction likely via serine palmitoylation. Moreover, the majority of the membrane-associated menin may reside inside membrane vesicles, as menin is protected from trypsin-mediated proteolysis, but disruption of the membrane fraction using detergent abolishes the detection. Consistently, cellular staining for menin also reveals the distribution of menin in the cell membrane and the punctate-like cell organelles. Our findings suggest that part of intracellular menin associates with the cell membrane peripherally as well as resides within the membrane vesicles. PMID- 26560944 TI - [History of Guillain-Barre Syndrome]. AB - Guillain-Barre syndrome (GBS) is an acute self-limited polyneuropathy named after Guillain, Barre, and Strohl, who first reported it in 1916. GBS was considered a demyelinating disease until the 1980s, when the acute axonal type of GBS was first reported. Since then, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy have been considered the two main subtypes of GBS. Autoimmunity underlies the pathogenesis of GBS. The presence of antibodies against various glycolipids in the acute-phase sera from patients with GBS has frequently been reported since the late 1980s. The effectiveness of plasmapheresis and intravenous immunoglobulin therapy has been established since the mid-1980s. However, severe or refractory cases still occur and further investigation is necessary for the development of novel treatments that are effective for such cases. PMID- 26560945 TI - [Epidemiology of Guillain-Barre Syndrome]. AB - The epidemiologic features of the Guillain-Barre syndrome (GBS) have been reported from North America, England, Iceland, and Norway before 1979. The population incidence rates of GBS fulfilling the NINCDS (National Institute of Neurological and Communicative Disorders and Stroke) criteria in USA, Canada, Italy, Spain, and Sweden ranged from 0.62 cases to 2.66 cases per 100,000 person years across all age groups, with a relative risk of 1.78 for males. GBS incidence increased by 20% for every 10-year increase in age. In Japan, the incidence of GBS was 1.15 per 100,000 person-years. Males were affected 1.5 times more frequently than females. The average age of patients with GBS was 39.1 +/- 20.0 years, which is lesser than that in North America and Europe. The relative ratio of the occurrence of Fisher syndrome among patients with GBS was higher than that in other Asian countries. PMID- 26560946 TI - [Clinical Phenotypes in Guillain-Barre Syndrome]. AB - Guillain-Barre syndrome can be classified into several phenotypes according to the type of predominantly disturbed nerve fibers, distribution of muscular weakness, and electrophysiological and pathological findings. Although several regional variants including Fisher syndrome and pharyngeal-cervical-brachial weakness were initially reported in Western researchers, many labor-intensive studies by Japanese researchers have significantly contributed to defining and highlighting these variants. This review summarizes the several regional variants of Guillain-Barre syndrome while highlighting the substantial contributions made by Japanese investigators. Furthermore, a new regional variant named "distal limb weakness" is proposed, in which regional weakness of hands and feet is observed throughout the disease course. It is considered a mild phenotype of acute axonal motor neuropathy after Campylobacter jejuni enteritis. PMID- 26560947 TI - [Neurophysiology in Guillain-Barre syndrome]. AB - The electrodiagnostic features for the demyelinating and axonal subtypes of Guillain-Barre syndrome (GBS) were described. In the early stage of demyelinating GBS, the most prominent neurophysiologic feature is the patchy demyelination in the peripheral nerves. Conduction slowing presents in the clinical recovery stage, which indicates the conduction slowing is due to mainly remyelination. Axonal GBS shows "reversible conduction failure", as well as primary axonal degeneration. "Reversible conduction failure" is thought to be the most common cause of the underestimation of axonal GBS. The electrodiagnostic criteria for GBS subtypes should be revised based on the knowledge acquired in recent years. PMID- 26560948 TI - [Pathology of the Peripheral Nervous System in Guillain-Barre Syndrome]. AB - Guillain-Barre syndrome is composed of two distinct clinicopathological entities: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and acute motor or motor and sensory axonal neuropathy (AMAN and AMSAN). AIDP is characterized by the patchily distributed demyelinative foci throughout the peripheral nervous system (PNS), whereas in AMAN/AMSAN primary axonal degeneration is observed in the PNS, particularly accentuated at the spinal nerve roots. The aim of this article is to provide an overview of previous findings regarding GBS pathology and thus, to elucidate the pathomechanisms of this life-threatening disorder. The most critical cause for AIDP may be the autoimmune attack on the Schwann cell membrane wrapping the myelinated nerve fibers, and that in AMAN/AMSAN may be an antibody-mediated attack on the axolemma at the nodes of Ranvier. PMID- 26560949 TI - [Molecular Mimicry and Guillain-Barre Syndrome]. AB - One-thirds of patients develop Guillain-Barre syndrome subsequent to Campylobacter jejuni enteritis. Molecular mimicry exists between C. jejuni lipo oligosaccharides and human peripheral nerve gangliosides GM1 and GD1a. IgG antibodies against GM1 or GD1a are produced in one out of 5,000 patients with C. jejuni enteritis. The autoantibodies bind to gangliosides at the nodes of Ranvier in the peripheral motor nerves and activate complement in situ. This is followed by the disappearance of the voltage-gated sodium channel clusters at the nodes and disruption of axo-glial junctions at the paranodes. This results in the development of motor nerve conduction failure and muscle weakness in the four limbs. PMID- 26560950 TI - [Autoantibodies in Guillain-Barre Syndrome]. AB - Serum antibodies against glycolipids, mainly gangliosides, are detected in about 60% of patients with Guillain-Barre syndrome (GBS) and its variants. Anti glycolipid antibodies play a crucial role in the pathogenic mechanisms of GBS. The antibody titer is the highest in the acute phase and decreases gradually. Molecular mimicries occur between the glycolipids and surface molecules on the infectious agents. Clinical subtypes of GBS are related to the antigenic specificities of the antibodies. The distribution of gangliosides in peripheral nervous tissues could explain the different clinical manifestations. The anti GQ1b antibody is detected in 80-90% of patients with Fisher syndrome characterized by ophthalmoplegia. GQ1b is localized in the paranodes of the human cranial nerves innervating the extraocular muscles. This is consistent with the clinical association between the anti-GQ1b antibody and ophthalmoplegia. The anti GM1 antibody is associated with acute motor axonal neuropathy, whereas the anti GD1b antibody is detected in acute sensory ataxic neuropathy. GBS animal models sensitized by gangliosides, such as GM1 or GD1b, develop monophasic peripheral neuropathies. In the animal models, disruption of molecule clusters and deposition of complement products were observed in the nodal and paranodal regions. Clinical and experimental data suggest complement-mediated pathogenic mechanisms triggered by anti-glycolipid antibodies in GBS. PMID- 26560951 TI - [Target Molecule for a Demyelinating Type of Guillain-Barre Syndrome, Acute Inflammatory Demyelinating Polyneuropathy]. AB - Guillain-Barre syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP. PMID- 26560952 TI - [Fisher Syndrome and Bickerstaff Brainstem Encephalitis]. AB - Fisher syndrome has been regarded as a peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered a pure central nervous system disease characterized by ophthalmoplegia, ataxia, and consciousness disturbance. Both disorders share common features including preceding infection, albumin cytological dissociation, and association with Guillain-Barre syndrome. The discovery of anti-GQ1b IgG antibodies further supports the view that the two disorders represent a single disease spectrum. The lesions in Fisher syndrome and Bickerstaff brainstem encephalitis are presumably determined by the expression of ganglioside GQ1b in the human peripheral and central nervous systems. Bickerstaff brainstem encephalitis is likely to represent a variant of Fisher syndrome with central nervous system involvement. PMID- 26560953 TI - [Acute Sensory Neuropathies and Acute Autonomic Neuropathies]. AB - From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barre syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies. PMID- 26560954 TI - [Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy]. AB - Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by an insidious onset showing progression over two months. However, up to 16% of CIDP patients may show acute presentation similar to Guillain-Barre syndrome (GBS). Such cases are termed acute-onset CIDP (A-CIDP). Distinguishing A-CIDP from GBS, especially the acute inflammatory demyelinating polyneuropathy (AIDP) subtype, is critical because therapeutic strategies and outcomes may differ between the two syndromes. Regarding clinical features, A-CIDP is less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with AIDP. Electrophysiological features are usually quite similar between the two, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy. Such a situation is termed treatment related fluctuation (TRF; GBS-TRF). The distinction between GBS-TRF and A-CIDP is an important clinical issue because maintenance treatment is often required in CIDP. The diagnosis of A-CIDP should be considered when the condition of a patient with GBS deteriorates after nine weeks from onset, or when deterioration occurs three times or more. PMID- 26560955 TI - [Treatment of Guillain-Barre Syndrome]. AB - The treatment of Guillain-Barre syndrome (GBS) was mainly symptomatic until the 1950s, followed by corticosteroid treatment in the 1950s through 1960s. Plasma exchange (PE) was then performed during 1970s through the 1980s, after which intravenous immunoglobulin (IVIg) was performed in 1990s through the 2000s. The effectiveness of IVIg and PE has been established by randomized controlled trial(RCT). Recently, new treatments using biological products have been explored. In this paper, we summarize the development of the treatment of GBS. PMID- 26560956 TI - [Prognostic Factors in Guillain-Barre Syndrome]. AB - Clinical outcome of Guillain-Barre syndrome (GBS) is poorer than may be expected, despite recent applications of plasmapheresis and IVIg. Among prognostic factors of GBS, clinical factors are more useful compared to electrophysiological or biological factors. To improve the outcome of GBS patients with poor prognoses, a worldwide prospective survey (IGOS, International GBS Outcome Study) and a Japanese prospective GBS outcome study (JGOS) have been conducted. These surveys make it possible to define biomarkers for disease activity and recovery, and to develop prognostic models to precisely predict the clinical course and outcome in individual patients in the early stage of the disease. PMID- 26560957 TI - [Novel Therapeutic Interventions in Guillain-Barre Syndrome: Review and Future Perspective]. AB - Intravenous immunoglobulin (IVIg) and plasma exchange (PE) are of proven efficacy and are considered the standard therapy for Guillain Barre syndrome (GBS). However, some patients require artificial ventilation during the acute phase and experience long-lasting neurological deficits or symptoms. Currently, there is no established therapeutic intervention for GBS other than IVIg and PE, even though a number of compounds have been investigated. Clinical trials to investigate the efficacy and safety of a second IVIg or eculizumab are ongoing. Increased understanding of the pathophysiology of GBS is expected to contribute to the development of a novel therapeutic approach. PMID- 26560958 TI - [Vitamin D in Multiple Sclerosis]. AB - The geographic epidemiology of multiple sclerosis (MS) suggests that low vitamin D levels are a modifiable risk factor. Previous studies have shown that patients with MS have significantly lower vitamin D levels compared with healthy controls. Vitamin D is a potent immunomodulator important for immune function and development, and it offers potential benefits by reducing inflammation. Vitamin D has beneficial effects in experimental autoimmune encephalomyelitis, an animal model of MS. In summation, these studies suggest that vitamin D may have therapeutic potential for MS. This has not been established although preliminary clinical trials for vitamin D in MS look promising. Genetic studies suggest that genes associated with vitamin D are critical susceptible genes for MS. In this review, we discuss current research investigating the association between vitamin D and MS and the issues that need to be resolved. PMID- 26560959 TI - [Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open Label Study]. AB - Following the first period of the multicenter, open-label, single-armed N01223 trial, the second period of the N01223 trial was conducted to evaluate long-term safety, along with the efficacy of adjunctive levetiracetam treatment (individualized dose range, 20-60 mg/kg/day or 1,000-3,000 mg/day) in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). Of the 62 children who completed the first period, 55 children [age: 10.4 +/- 3.4 years (mean +/- standard deviation)] were elected to enter the second period for a maximum of 39 months. Twenty children were withdrawn during this second period. Frequencies of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 98.2% (54/55 cases) and 27.3% (15/55 cases), respectively. The most common TEAEs were nasopharyngitis (76.4%), influenza (36.4%) and pyrexia (25.5%). The only frequent ADR (>2%) was somnolence (3.6%). Although serious TEAEs and death were reported in 8 cases and 1 case (drowning), respectively, a serious ADR was only reported in 1 case (vomiting). The median percentage reduction and 50% response rate for POS were 43.32% and 41.8%, respectively. One child showed a maximum seizure-free period of 163 days. In conclusion, levetiracetam demonstrated long-term safety and good tolerance with beneficial efficacy as an adjunctive therapy in Japanese children with uncontrolled POS. (Received June 30, 2015; Accepted July 14, 2015: Published November 1, 2015). PMID- 26560960 TI - [A Case of Musicophilia with Right Predominant Temporal Lobe Atrophy]. AB - A 68-year-old woman exhibiting musicophilia with right predominant temporal lobe atrophy happened to visit our clinic. She had no musical background, but beginning two years ago, she acquired a strong preference for especially popular music and sometimes sang at home. She did not exhibit obvious semantic aphasia or facial agnosia, and showed only mild behavioral changes including apathy. Her musicophilia can be explained as an instance of stereotypical behavior. Her right temporal lobe atrophy may have caused changes in her emotional and reward systems, resulting in her music specific behaviors. PMID- 26560961 TI - Effects of Lipid Composition on Bilayer Membranes Quantified by All-Atom Molecular Dynamics. AB - Biological bilayer membranes typically contain varying amounts of lamellar and nonlamellar lipids. Lamellar lipids, such as dioleoylphosphatidylcholine (DOPC), are defined by their tendency to form the lamellar phase, ubiquitous in biology. Nonlamellar lipids, such as dioleoylphosphatidylethanolamine (DOPE), prefer instead to form nonlamellar phases, which are mostly nonbiological. However, nonlamellar lipids mix with lamellar lipids in biomembrane structures that remain overall lamellar. Importantly, changes in the lamellar vs nonlamellar lipid composition are believed to affect membrane function and modulate membrane proteins. In this work, we employ atomistic molecular dynamics simulations to quantify how a range of bilayer properties are altered by variations in the lamellar vs nonlamellar lipid composition. Specifically, we simulate five DOPC/DOPE bilayers at mixing ratios of 1/0, 3/1, 1/1, 1/3, and 0/1. We examine properties including lipid area and bilayer thickness, as well as the transmembrane profiles of electron density, lateral pressure, electric field, and dipole potential. While the bilayer structure is only marginally altered by lipid composition changes, dramatic effects are observed for the lateral pressure, electric field, and dipole potential profiles. Possible implications for membrane function are discussed. PMID- 26560962 TI - Checkpoint inhibitors in Hodgkin's lymphoma. AB - Hodgkin's lymphoma is unusual among cancers in that it consists of a small number of malignant Hodgkin/Reed-Sternberg cells in a sea of immune system cells, including T cells. Most of these T cells are reversibly inactivated in different ways and their reactivation may induce a very strong immune response to cancer cells. One way of reactivation of T cells is with antibodies blocking the CTLA-4 and especially with antibodies directed against PD-1 or the PD-L1 ligand thereby reversing the tumor-induced downregulation of T-cell function and augmenting antitumor immune activity at the priming (CTLA-4) or tissue effector (PD-1) phase. Immune checkpoint inhibitors have been evidenced as an additional treatment option with substantial effectiveness and acceptable toxicity in heavily pretreated patients with Hodgkin's lymphoma. Particularly, PD-1 blockade with nivolumab and pembrolizumab has demonstrated significant single-agent activity in this select population. PMID- 26560963 TI - Preliminary Evidence Suggests Periureteral Botulinum Toxin Type A Injection Improves Ureteral Stone Passage in the Porcine Model. AB - PURPOSE: We evaluated the use of periureteral injection of botulinum toxin type A (Botox((r)), BTX-A) to facilitate passage of ureteral stones in a porcine model. We believe that reducing detrusor muscle tone around the intramural ureter may facilitate passage of ureteral stones through the ureterovesical junction. MATERIALS AND METHODS: With complete Institutional Animal Care and Use Committee approval, artificial stones (BegoStone plus) were placed by retrograde ureteroscopy into the proximal ureter using fluoroscopic guidance using an in vivo porcine model. Six animals underwent periureteral BTX-A injection 30 U/mL to three locations around the ureteral orifice, and six animals were in the control group undergoing periureteral injection of physiologic saline. RESULTS: There was a significant decrease in time to stone passage in the BTX-A group compared with the control group, 2.6 +/- 1.3 vs 6.8 +/- 2.9 days, respectively (p = 0.018). None of the animals had evidence of vesicoureteral reflux postprocedure (N = 0/12). CONCLUSIONS: Preliminary results suggest that periureteral injection of BTX-A facilitates ureteral stone passage in this model. BTX-A may provide a simple, office-based endoscopic treatment option for ureteral stones. Further studies would be necessary to evaluate its efficacy in humans compared with traditional medical expulsive therapy. PMID- 26560964 TI - Severe learning deficits of IRSp53 mutant mice are caused by altered NMDA receptor-dependent signal transduction. AB - Learning and memory is dependent on postsynaptic architecture and signaling processes in forebrain regions. The insulin receptor substrate protein of 53 kDa (IRSp53, also known as Baiap2) is a signaling and adapter protein in forebrain excitatory synapses. Mice deficient in IRSp53 display enhanced levels of postsynaptic N-methyl-D-aspartate receptors (NMDARs) and long-term potentiation (LTP) associated with severe learning deficits. In humans, reduced IRSp53/Baiap2 expression is associated with a variety of neurological disorders including autism, schizophrenia, and Alzheimer's disease. Here, we analyzed mice lacking one copy of the gene coding for IRSp53 using behavioral tests including contextual fear conditioning and the puzzle box. We show that a 50% reduction in IRSp53 levels strongly affects the performance in fear-evoking learning paradigms. This correlates with increased targeting of NMDARs to the postsynaptic density (PSD) in hippocampi of both heterozygous and knock out (ko) mice at the expense of extrasynaptic NMDARs. As hippocampal NMDAR-dependent LTP is enhanced in IRSp53-deficient mice, we investigated signaling cascades important for the formation of fear-evoked memories. Here, we observed a dramatic increase in cAMP response element-binding protein-dependent signaling in heterozygous and IRSp53 deficient mice, necessary for the transcriptional dependent phase of LTP. In contrast, activation of the MAPK and Akt kinase pathways required for translation dependent phase of LTP are reduced. Our data suggest that loss or even the reduction in IRSp53 increases NMDAR-dependent cAMP responsive element-binding protein activation in the hippocampus, and interferes with the ability of mice to learn upon anxiety-related stimuli. We show here that a moderate reduction in the postsynaptic protein IRSp53 in mice leads to an increase in postsynaptic NMDA receptors. Both in heterozygous and IRSp53 deficient mice, this is associated with altered postsynaptic signal transduction, and poor performance of mice in fear-associated learning paradigms, indicating that precise control of postsynaptic NMDA receptor density is essential for memory formation. PMID- 26560965 TI - Efficacy of Intraoperative Neuro-Monitoring to Localize the External Branch of the Superior Laryngeal Nerve. AB - BACKGROUND: This study investigated whether visual localization of the external branch of the superior laryngeal nerve (EBSLN) coincides with its localization via intraoperative neuro-monitoring (IONM) during thyroidectomy and whether its use influences the frequency of injuries. METHODS: A prospective, comparative, cross-sectional, observational study was performed in 240 superior thyroid poles. The metrics were visual identification of the EBSLN and its corroboration with IONM. The frequency of EBSLN injuries was also determined. Statistical analysis was achieved via kappa and chi-square tests, as well as odds ratios (OR). RESULTS: Of the 240 superior thyroid poles, IONM identified 234 (97.5%) EBSLN, whereas 190 (79.1%) were identified visually: OR = 10.35 [CI 4.37-24.65] p < 0.0001. Of the 190 EBSLN identified visually, 150 were confirmed through IONM. Indeed, their structure corresponded to an EBSLN to yield a kappa with a linear weighting value of 0.362. The standard error was 0.0467 [CI 0.2686-0.4554], indicating a fair agreement between the visual and IONM classification. CONCLUSION: IONM identified 97.5% of EBSLN cases. It was higher than the visual identification. There were no injuries to EBSLN identified through IONM. PMID- 26560966 TI - Alcohol-attributable healthcare attendances up to 10 years prior to diagnosis of alcoholic cirrhosis: a population based case-control study. AB - BACKGROUND & AIMS: Cirrhosis because of alcohol could be avoided if drinking behaviour could be altered earlier in the disease course. Our aim was to quantify the burden of morbidities in patients prior to alcoholic cirrhosis diagnosis, as this may inform the earlier identification of people at high risk for targeted interventions. METHODS: We carried out a case-control study using 2479 incident cases of alcoholic cirrhosis and 24 790 controls identified from 357 primary and secondary care centres in England. We assessed the prevalence of morbidities that are partly attributable to alcohol (namely malignant neoplasms, diabetes, epilepsy, injuries, cardiovascular and digestive diseases) prior to alcoholic cirrhosis diagnosis. We compared prevalence in cases to the control population and used logistic regression to derive odds ratios (95% CI). RESULTS: Fifty-eight per cent of cases compared to 29% of controls had had at least one alcohol attributable condition before cirrhosis diagnosis. The most frequent conditions (proportion in cases vs. controls) were intentional injuries (35.9% vs. 11.9%) and cardiovascular diseases (23.2% vs. 15.6%), followed by diabetes (12.8% vs. 5.3%), digestive diseases (6.1% vs. 1.2%) and epilepsy (5.0% vs. 1.1%). The strongest association with alcoholic cirrhosis was found for digestive diseases [OR 5.4 (4.4-6.7)], epilepsy [OR: 4.4 (3.5-5.5)] and injuries [OR: 4.0 (3.7-4.4)] particularly among those aged 18-44 years. CONCLUSION: These data highlight the high burden of other alcohol-attributable conditions in patients prior to alcoholic cirrhosis diagnosis. Reviewing those consistently presenting with any of these conditions more closely could help practitioners reduce/avoid the long term consequences of development of alcoholic liver disease. PMID- 26560967 TI - Trends in Genital Warts in the Era of Human Papillomavirus Vaccination. PMID- 26560968 TI - Likeability of Garden Birds: Importance of Species Knowledge & Richness in Connecting People to Nature. AB - Interacting with nature is widely recognised as providing many health and well being benefits. As people live increasingly urbanised lifestyles, the provision of food for garden birds may create a vital link for connecting people to nature and enabling them to access these benefits. However, it is not clear which factors determine the pleasure that people receive from watching birds at their feeders. These may be dependent on the species that are present, the abundance of individuals and the species richness of birds around the feeders. We quantitatively surveyed urban households from towns in southern England to determine the factors that influence the likeability of 14 common garden bird species, and to assess whether people prefer to see a greater abundance of individuals or increased species richness at their feeders. There was substantial variation in likeability across species, with songbirds being preferred over non songbirds. Species likeability increased for people who fed birds regularly and who could name the species. We found a strong correlation between the number of species that a person could correctly identify and how connected to nature they felt when they watched garden birds. Species richness was preferred over a greater number of individuals of the same species. Although we do not show causation this study suggests that it is possible to increase the well-being benefits that people gain from watching birds at their feeders. This could be done first through a human to bird approach by encouraging regular interactions between people and their garden birds, such as through learning the species names and providing food. Second, it could be achieved through a bird to human approach by increasing garden songbird diversity because the pleasure that a person receives from watching an individual bird at a feeder is dependent not only on its species but also on the diversity of birds at the feeder. PMID- 26560969 TI - Polysilicon nanogap lab-on-chip facilitates multiplex analyses with single analyte. AB - Rationally designed biosensing system supports multiplex analyses is warranted for medical diagnosis to determine the level of analyte interaction. The chemically functionalized novel multi-electrode polysilicon nanogap (PSNG) lab-on chip is designed in this study, facilitates multiplex analyses for a single analyte. On the fabricated 69nm PSNG, biocompatibility and structural characteristics were verified for the efficient binding of Human Chorionic Gonadotropin (hCG). With the assistance of microfluidics, hCG sample was delivered via single-injection to 3-Aminopropyl(triethoxy)silane (APTES) and Glycidoxypropyl(trimethoxy)silane (GPMS) modified PSNG electrodes and the transduced signal was used to investigate the dielectric mechanisms for multiplex analyses. The results from amperometric response and impedance measurement delivered the scale of interaction between anti-hCG antibody and hCG that exhibited 6.5 times higher sensitivity for the chemical linker, APTES than GPMS. Under optimized experimental conditions, APTES and GPMS modified immunosensor has a limit of detection as 0.56mIU/ml and 2.93mIU/ml (at S/N=3), with dissociation constants (Kd) of 5.65+/-2.5mIU/ml and 7.28+/-2.6mIU/ml, respectively. These results suggest that multiplex analysis of single target could enhance the accuracy of detection and reliable for real-time comparative analyses. The designed PSNG is simple, feasible, requires low sample consumption and could be applied for any given multiplex analyses. PMID- 26560970 TI - Validation of Self-Management Screening (SeMaS), a tool to facilitate personalised counselling and support of patients with chronic diseases. AB - BACKGROUND: A rising number of people with chronic conditions is offered interventions to enhance self-management. The responsiveness of individuals to these interventions depends on patient characteristics. We aimed to develop and validate a tool to facilitate personalised counselling and support for self management in patients with chronic diseases in primary care. METHODS: We drafted a prototype of the tool for Self-Management Screening (SeMaS), comprising 27 questions that were mainly derived from validated questionnaires. To reach high content validity, we performed a literature review and held focus groups with patients and healthcare professionals as input for the tool. The characteristics self-efficacy, locus of control, depression, anxiety, coping, social support, and perceived burden of disease were incorporated into the tool. Three items were added to guide the type of support or intervention, being computer skills, functioning in groups, and willingness to perform self-monitoring. Subsequently, the construct and criterion validity of the tool were investigated in a sample of 204 chronic patients from two primary care practices. Patients filled in the SeMaS and a set of validated questionnaires for evaluation of SeMaS. The Patient Activation Measure (PAM-13), a generic instrument to measure patient health activation, was used to test the convergent construct validity. RESULTS: Patients had a mean age of 66.8 years and 46.6 % was female. 5.9 % did not experience any barrier to self-management, 28.9 % experienced one minor or major barrier, and 30.4 % two minor or major barriers. Compared to the criterion measures, the positive predictive value of the SeMaS characteristics ranged from 41.5 to 77.8 % and the negative predictive value ranged from 53.3 to 99.4 %. Crohnbach's alpha for internal consistency ranged from 0.56 to 0.87, except for locus of control (alpha = 0.02). The regression model with PAM-13 as a dependent variable showed that the SeMaS explained 31.7 % (r(2) = 0.317) of the variance in the PAM-13 score. CONCLUSIONS: SeMaS is a short validated tool that can signal potential barriers for self-management that need to be addressed in the dialogue with the patient. As such it can be used to facilitate personalised counselling and support to enhance self-management in patients with chronic conditions in primary care. PMID- 26560971 TI - GRADE in Systematic Reviews of Acupuncture for Stroke Rehabilitation: Recommendations based on High-Quality Evidence. AB - Systematic reviews (SRs) of randomized controlled trials (RCTs) have demonstrated acupuncture's effectiveness in stroke rehabilitation. The current study reviews the quality of evidence in SRs of acupuncture in stroke rehabilitation, and rates the strength of recommendation for its use based on this evidence using the GRADE (grading of recommendations, assessment, development and evaluations) approach. A comprehensive literature search was performed using multiple databases (e.g., Medline, Embase) with advanced search strategies. Two authors independently selected articles, collected data, and assessed the methodological quality of each identified SR according to AMSTAR (a measurement tool to assess systematic reviews) and OQAQ (Oxman and Guyatt's overview quality assessment questionnaire). Outcomes related to stroke rehabilitation were evaluated. SRs of high methodological quality (AMSTAR score >=9 and OQAQ score >=7) were graded using GRADE. Ultimately, acupuncture yields benefits in stroke rehabilitation (neurological function improvement: RR = 1.34; swallowing improvement: RR = 1.61, 1.49, 1.07; disability: SMD = 0.49 or 0.07). Poor evidentiary quality and insufficient information about harm led to weak recommendations. In conclusion, acupuncture may improve stroke rehabilitation, as the GRADE approach indicated a weak recommendation for acupuncture's usage in this context. PMID- 26560972 TI - Nanomesh-Type Graphene Superlattice on Au(111) Substrate. AB - The adherence of graphene to various crystalline substrates often leads to a periodic out-of-plane modulation of its atomic structure due to the lattice mismatch. While, in principle, convex (protrusion) and concave (depression) superlattice geometries are nearly equivalent, convex superlattices have predominantly been observed for graphene on various metal surfaces. Here we report the STM observation of a graphene superlattice with concave (nanomesh) morphology on Au(111). DFT and molecular dynamics simulations confirm the nanomesh nature of the graphene superlattice on Au(111) and also reveal its potential origin as a surface reconstruction, consisting of the imprinting of the nanomesh morphology into the Au(111) surface. This unusual surface reconstruction can be attributed to the particularly large mobility of the Au atoms on Au(111) surfaces and most probably plays an important role in stabilizing the concave graphene superlattice. We report the simultaneous observation of both convex and concave graphene superlattices on herringbone reconstructed Au(111) excluding the contrast inversion as the origin of the observed concave morphology. The observed graphene nanomesh superlattice can provide an intriguing nanoscale template for self-assembled structures and nanoparticles that cannot be stabilized on other surfaces. PMID- 26560973 TI - Oestradiol Exposure Early in Life Programs Daily and Circadian Activity Rhythms in Adult Mice. AB - Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild-type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1-5E and p1-5OIL , respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the 'master oscillator'. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1-5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1-5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1-5E in WT and ArKO females but not males. P1-5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1-5E altered the magnitude of photic-induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and circadian activity rhythms throughout life. PMID- 26560974 TI - The Transcriptomic Response of Arabidopsis thaliana to Zinc Oxide: A Comparison of the Impact of Nanoparticle, Bulk, and Ionic Zinc. AB - The impact of nanosize was evaluated by comparing of the transcriptomic response of Arabidopsis thaliana roots to ZnO nanoparticles (nZnO), bulk ZnO, and ionic Zn(2+). Microarray analyses revealed 416 up- and 961 down-regulated transcripts (expression difference >2-fold, p [FDR] < 0.01) after a seven-day treatment with nZnO (average particle size 20 nm, concentration 4 mg L(-1)). Exposure to bulk ZnO resulted in 816 up- and 2179 down-regulated transcripts. The most dramatic changes (1711 transcripts up- and 3242 down-regulated) were caused by the presence of ionic Zn(2+) (applied as ZnSO4.7H20 at a concentration of 14.14 mg L( 1), corresponding to the amount of Zn contained in 4 mg L(-1) ZnO). Genes involved in stress response (e.g., to salt, osmotic stress or water deprivation) were the most relatively abundant group of gene transcripts up-regulated by all three Zn treatments while genes involved in cell organization and biogenesis (e.g., tubulins, arabinogalactan proteins) and DNA or RNA metabolism (e.g., histones) were the most relatively abundant groups of down-regulated transcripts. The similarity of the transcription profiles and the increasing number of changed transcripts correlating with the increased concentration of Zn(2+) in cultivation medium indicated that released Zn(2+) may substantially contribute to the toxic effect of nZnO because particle size has not demonstrated a decisive role. PMID- 26560975 TI - Correction: Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock. AB - Vol. 110 (4): 453-460, 2015. p. 453. "Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock" should read: "Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock". == Vol. 110 (6): 797-800, 2015 .p. 797. "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E 26/110.497/2011), CNPq (458858/2014-5)" should read: "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5),FAPEAM/CNPq/PPP-FAPEAM (010/2011), MCT/CNPq (014/2011)" PMID- 26560976 TI - Surveillance, health promotion and control of Chagas disease in the Amazon Region -Medical attention in the Brazilian Amazon Region: a proposal. AB - We refer to Oswaldo Cruz's reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care. PMID- 26560978 TI - Viral aetiology of common colds of outpatient children at primary care level and the use of antibiotics. AB - Although antibiotics are ineffective against viral respiratory infections, studies have shown high rates of prescriptions worldwide. We conducted a study in Brazil to determine the viral aetiologies of common colds in children and to describe the use of antibiotics for these patients. Children up to 12 years with common colds were enrolled from March 2008-February 2009 at a primary care level facility and followed by regular telephone calls and medical consultations. A nasopharyngeal wash was obtained at enrollment and studied by direct fluorescence assay and polymerase chain reaction for nine different types of virus. A sample of 134 patients was obtained, median age 2.9 years (0.1-11.2 y). Respiratory viruses were detected in 73.9% (99/134) with a coinfection rate of 30.3% (30/99). Rhinovirus was the most frequent virus (53/134; 39.6%), followed by influenza (33/134; 24.6%) and respiratory syncytial virus (8/134; 13.4%). Antibiotic prescription rate was 39.6% (53/134) and 69.8% (37/53) were considered inappropriate. Patients with influenza infection received antibiotics inappropriately in a greater proportion of cases when compared to respiratory syncytial virus and rhinovirus infections (p = 0.016). The rate of inappropriate use of antibiotics was very high and patients with influenza virus infection were prescribed antibiotics inappropriately in a greater proportion of cases. PMID- 26560979 TI - Identification of the nicotinamide mononucleotide adenylyltransferase of Trypanosoma cruzi. AB - The intracellular parasite Trypanosoma cruzi is the aetiological agent of Chagas disease, a public health concern with an increasing incidence rate. This increase is due, among other reasons, to the parasite's drug resistance mechanisms, which require nicotinamide adenine dinucleotide (NAD+). Furthermore, this molecule is involved in metabolic and intracellular signalling processes necessary for the survival of T. cruzi throughout its life cycle. NAD+biosynthesis is performed by de novo and salvage pathways, which converge on the step that is catalysed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) (enzyme commission number: 2.7.7.1). The identification of the NMNAT of T. cruzi is important for the development of future therapeutic strategies to treat Chagas disease. In this study, a hypothetical open reading frame (ORF) for NMNAT was identified in the genome of T. cruzi.The corresponding putative protein was analysed by simulating structural models. The ORF was amplified from genomic DNA by polymerase chain reaction and was further used for the construction of a corresponding recombinant expression vector. The expressed recombinant protein was partially purified and its activity was evaluated using enzymatic assays. These results comprise the first identification of an NMNAT in T. cruzi using bioinformatics and experimental tools and hence represent the first step to understanding NAD+ metabolism in these parasites. PMID- 26560977 TI - Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors. AB - Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted. PMID- 26560980 TI - Widespread nasal carriage of Mycobacterium lepraeamong a healthy population in a hyperendemic region of northeastern Brazil. AB - A case-control study was conducted to determine the presence ofMycobacterium lepraeDNA in nasal secretions of leprosy cases and nonleprosy individuals in Fortaleza, Brazil. It included 185 cases identified by physicians at the Dona Libania National Reference Centre for Sanitary Dermatology (CDERM). A control group (Co) (n = 136) was identified among individuals from CDERM not diagnosed as leprosy cases. To augment the spatial analysis of M. leprae specific repetitive element (RLEP) positive prevalence, an external group (EG) (n = 121), a convenience sample of healthy students, were included. Polymerase chain reaction for the RLEP sequence was conducted for all participants. Prevalence of RLEP positivity for cases and Co were 69.2% and 66.9%, respectively, significantly higher than for EG (28.1%), and reported elsewhere. Male sex, belonging to a lower socioeconomic status (D/E), history of a previous contact with a case and being older, were associated with being a leprosy case. Our geographical analysis demonstrated that the bacillus is widespread among the healthy population, with clusters of RLEP positive multibacillary cases concentrated in distinct areas of the city. Our results suggest that in endemic areas, as in Fortaleza, surveillance for both nonhousehold leprosy contacts and members of the general population living in cluster areas should be implemented. PMID- 26560981 TI - Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part II: experimental studies withAspidosperma ramiflorum in vivo and in vitro. AB - Several species of Aspidosperma plants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellow peroba, coffee-peroba and matiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorum extracts, the plant activity against Plasmodium falciparum was evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 ug/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium berghei in mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required. PMID- 26560982 TI - Multibacillary leprosy patients with high and persistent serum antibodies to leprosy IDRI diagnostic-1/LID-1: higher susceptibility to develop type 2 reactions. AB - Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient's bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R. PMID- 26560983 TI - Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline--a longitudinal analysis after using TNFa blockers. AB - Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI. PMID- 26560984 TI - Waterborne toxoplasmosis investigated and analysed under hydrogeological assessment: new data and perspectives for further research. AB - We present a set of data on human and chicken Toxoplasma gondii seroprevalence that was investigated and analysed in light of groundwater vulnerability information in an area endemic for waterborne toxoplasmosis in Brazil. Hydrogeological assessment was undertaken to select sites for water collection from wells for T. gondii oocyst testing and for collecting blood from free-range chickens and humans for anti-T. gondii serologic testing. Serologic testing of human specimens was done using conventional commercial tests and a sporozoite specific embryogenesis-related protein (TgERP), which is able to differentiate whether infection resulted from tissue cysts or oocysts. Water specimens were negative for the presence of viable T. gondii oocysts. However, seroprevalence in free-range chickens was significantly associated with vulnerability of groundwater to surface contamination (p < 0.0001; odds ratio: 4.73, 95% confidence interval: 2.18-10.2). Surprisingly, a high prevalence of antibodies against TgERP was detected in human specimens, suggesting the possibility of a continuous contamination of drinking water with T. gondii oocysts in this endemic setting. These findings and the new proposed approach to investigate and analyse endemic toxoplasmosis in light of groundwater vulnerability information associated with prevalence in humans estimated by oocyst antigens recognition have implications for the potential role of hydrogeological assessment in researching waterborne toxoplasmosis at a global scale. PMID- 26560985 TI - Risk factors associated with Trypanosoma cruzi exposure in domestic dogs from a rural community in Panama. AB - Chagas disease, caused by Trypanosoma cruzi infection, is a zoonosis of humans, wild and domestic mammals, including dogs. In Panama, the main T. cruzi vector is Rhodnius pallescens, a triatomine bug whose main natural habitat is the royal palm, Attalea butyracea. In this paper, we present results from three T. cruzi serological tests (immunochromatographic dipstick, indirect immunofluorescence and ELISA) performed in 51 dogs from 24 houses in Trinidad de Las Minas, western Panama. We found that nine dogs were seropositive (17.6% prevalence). Dogs were 1.6 times more likely to become T. cruzi seropositive with each year of age and 11.6 times if royal palms where present in the peridomiciliary area of the dog's household or its two nearest neighbours. Mouse-baited-adhesive traps were employed to evaluate 12 peridomestic royal palms. All palms were found infested with R. pallescens with an average of 25.50 triatomines captured per palm. Of 35 adult bugs analysed, 88.6% showed protozoa flagellates in their intestinal contents. In addition, dogs were five times more likely to be infected by the presence of an additional domestic animal species in the dog's peridomiciliary environment. Our results suggest that interventions focused on royal palms might reduce the exposure to T. cruzi infection. PMID- 26560986 TI - Synthesis of biocompatible polymeric nano-capsules based on calcium carbonate: A potential cisplatin delivery system. PMID- 26560988 TI - Bowel obstruction secondary to incarcerated obturator hernia. AB - BACKGROUND/OBJECTIVE: Obturator hernia is rare type of abdominal hernia and its diagnosis usually is made intraoperatively for bowel obstruction or computed tomography (CT) scans of the abdomen. The aim of this study was to review patient's records with respect to clinical manifestation, CT scan findings, and operative outcomes. METHODS: From April 2009 to January 2015, six female patients with incarcerated obturator hernia underwent urgent operation for acute intestinal obstruction. The medical records were reviewed with respect to clinical manifestation, findings of CT scan and the outcomes of operation. RESULTS: The median age of patients was 83 years (range, 79-87 years) and the body mass index was 21.61 +/- 0.52 kg/m2. CT scans of abdomen demonstrated that intestinal obstruction secondary to obturator hernia, consistency with operative findings. Partial bowel resection was performed in two of six patients because of necrosis of incarcerated obturator hernia. The hernia was repaired with interrupted sutures. Lung infection occurred in one patient, and wound infection in another. One recurrence was observed and two patients died from the unrelated diseases during the period of follow-up. CONCLUSION: The diagnosis of obturator hernia can be made by CT scan preoperatively, and the obturator hernia should be suspected when an unexplained bowel obstruction in elderly, thin women occurs. PMID- 26560987 TI - Effects of low-dose morphine on perceived sleep quality in patients with refractory breathlessness: A hypothesis generating study. AB - BACKGROUND AND OBJECTIVE: The management of chronic refractory breathlessness is one of the indications for regular low-dose (<=30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. METHODS: This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 +/- 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. RESULTS: Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). CONCLUSION: Four days of low dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality. PMID- 26560989 TI - Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma. AB - Radiation therapy (RT) may be suitable for treating patients with hepatocellular carcinoma (HCC) who are difficult to treat with any other option. However, it remains unclear whether RT extends survival in these patients. Among the 957 HCC patients treated at Tohoku University Hospital from January 2007 to December 2013, only 49 patients received RT. We therefore retrospectively analyzed the outcomes of these patients; they were divided into three groups based on the reasons for choosing RT: 27 patients at Stage IV A (67.1 +/- 1.6 years, 50.5 +/- 2.1 Gy), 9 patients with alternative therapy (72.2 +/- 2.4 years, 58.9 +/- 1.1 Gy), and 13 patients who received RT after transarterial chemoembolization (TACE) (75.6 +/- 2.1 years, 56.5 +/- 1.5 Gy). RT was employed to ensure the local control of the lesion. The patients at Stage IV A were treated with radical RT (n = 16) or with palliative RT (n = 11). In radical RT group, the response rate was 37.5% and the complete response rate was 25%. The survival rate was 12.5 +/- 2.6 months after radical RT. This is considered relatively good for Stage IV A. The disease-free survival rate was 13.0 +/- 2.8 months after RT. This excellent disease-free survival indicates that RT is an alternative to other treatments. In the TACE group, patients who received the RT had the significantly long disease free survival rate than only-TACE (18.0 +/- 3.8 months vs. 11.2 +/- 0.58 months). We propose that RT is effective and safe for HCC. PMID- 26560990 TI - Early studies reported extreme findings with large variability: a meta epidemiologic study in the field of endocrinology. AB - OBJECTIVES: To evaluate the presence of extreme findings and fluctuation in effect size in endocrinology. STUDY DESIGN AND SETTINGS: We systematically identified all meta-analyses published in 2014 in the field of endocrinology. Within each meta-analysis, the effect size of the primary binary outcome was compared across studies according to their order of publication. We pooled studies using the DerSimonian and Laird random-effects method. Heterogeneity was evaluated using the I(2) and tau(2). RESULTS: Twelve percent of the included 100 meta-analyses reported the largest effect size in the very first published study. The largest effect size occurred in the first 2 earliest studies in 31% of meta analyses. When the effect size was the largest in the first published study, it was three times larger than the final pooled effect (ratio of rates, 3.26; 95% confidence interval: 1.80, 5.90). The largest heterogeneity measured by I(2) was observed in 18% of the included meta-analyses when combining the first 2 studies or 17% when combing the first 3 studies. CONCLUSIONS: In endocrinology, early studies reported extreme findings with large variability. This behavior of the evidence needs to be taken into account when used to formulate clinical policies. PMID- 26560991 TI - Data on the distribution of cancer incidence and death across age and sex groups visualized using multilevel spie charts. AB - Cancer incidence and death statistics are typically recorded for multiple age and sex brackets, leading to large data tables which are difficult to digest. Effective visualizations of this data would allow practitioners, policy makers, and the general public to comprehend the data more readily and act on it appropriately. We introduce multilevel spie charts to create a combined visualization of cancer incidence and death statistics. Spie charts combine multiple pie charts, where the base pie chart (representing the general population) is used to set the angles of slices, and the superimposed ones use variable radii to portray the cancer data. Spie charts of cancer incidence and death statistics from Israel for 2009-2011 are used as an illustration. These charts clearly show various patterns of how cancer incidence and death distribute across age and sex groups, illustrating (1) absolute numbers and (2) rates per 100,000 population for different age and sex brackets. In addition, drawing separate charts for different cancer types illustrates relative mortality, both (3) across cancer types and (4) mortality relative to incidence. Naturally, this graphical depiction can be used for other diseases as well. PMID- 26560992 TI - Systematic reviews experience major limitations in reporting absolute effects. AB - OBJECTIVES: Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify and describe the reporting and methods for calculating absolute effect estimates in SRs. STUDY DESIGN AND SETTING: Two reviewers independently screened title, abstract, and full text and extracted data from a sample of Cochrane and non-Cochrane SRs. We used regression analyses to examine the association between study characteristics and the reporting of absolute estimates for the most patient-important outcome. RESULTS: We included 202 SRs (98 Cochrane and 104 non-Cochrane), most of which (92.1%) included standard meta-analyses including relative estimates of effect. Of the 202 SRs, 73 (36.1%) reported absolute effect estimates for the most patient-important outcome. SRs with statistically significant effects were more likely to report absolute estimates (odds ratio, 2.26; 95% confidence interval: 1.08, 4.74). The most commonly reported absolute estimates were: for each intervention, risk of adverse outcomes expressed as a percentage (41.1%); number needed to treat (26.0%); and risk for each intervention expressed as natural units or natural frequencies (24.7%). In 12.3% of the SRs that reported absolute effect estimates for both benefit and harm outcomes, harm outcomes were reported exclusively as absolute estimates. Exclusively reporting of beneficial outcomes as absolute estimates occurred in 6.8% of the SRs. CONCLUSIONS: Most SRs do not report absolute effects. Those that do often report them inadequately, thus requiring users of SRs to generate their own estimates of absolute effects. For any apparently effective or harmful intervention, SR authors should report both absolute and relative estimates to optimize the interpretation of their findings. PMID- 26560993 TI - Automated image analysis with the potential for process quality control applications in stem cell maintenance and differentiation. AB - The translation of laboratory processes into scaled production systems suitable for manufacture is a significant challenge for cell based therapies; in particular there is a lack of analytical methods that are informative and efficient for process control. Here the potential of image analysis as one part of the solution to this issue is explored, using pluripotent stem cell colonies as a valuable and challenging exemplar. The Cell-IQ live cell imaging platform was used to build image libraries of morphological culture attributes such as colony "edge," "core periphery" or "core" cells. Conventional biomarkers, such as Oct3/4, Nanog, and Sox-2, were shown to correspond to specific morphologies using immunostaining and flow cytometry techniques. Quantitative monitoring of these morphological attributes in-process using the reference image libraries showed rapid sensitivity to changes induced by different media exchange regimes or the addition of mesoderm lineage inducing cytokine BMP4. The imaging sample size to precision relationship was defined for each morphological attribute to show that this sensitivity could be achieved with a relatively low imaging sample. Further, the morphological state of single colonies could be correlated to individual colony outcomes; smaller colonies were identified as optimum for homogenous early mesoderm differentiation, while larger colonies maintained a morphologically pluripotent core. Finally, we show the potential of the same image libraries to assess cell number in culture with accuracy comparable to sacrificial digestion and counting. The data supports a potentially powerful role for quantitative image analysis in the setting of in-process specifications, and also for screening the effects of process actions during development, which is highly complementary to current analysis in optimization and manufacture. PMID- 26560994 TI - Decreased Gap Width in a Cylindrical High-Field Asymmetric Waveform Ion Mobility Spectrometry Device Improves Protein Discovery. AB - High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas phase ions according to their characteristic dependence of ion mobility on electric field strength. FAIMS can be implemented as a means of automated gas-phase fractionation in liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments. We modified a commercially available cylindrical FAIMS device by enlarging the inner electrode, thereby narrowing the gap and increasing the effective field strength. This modification provided a nearly 4-fold increase in FAIMS peak capacity over the optimally configured unmodified device. We employed the modified FAIMS device for on-line fractionation in a proteomic analysis of a complex sample and observed major increases in protein discovery. NanoLC-FAIMS MS/MS of an unfractionated yeast tryptic digest using the modified FAIMS device identified 53% more proteins than were identified using an unmodified FAIMS device and 98% more proteins than were identified with unaided nanoLC-MS/MS. We describe here the development of a nanoLC-FAIMS-MS/MS protocol that provides automated gas-phase fractionation for proteomic analysis of complex protein digests. We compare this protocol against prefractionation of peptides with isoelectric focusing and demonstrate that FAIMS fractionation yields comparable protein recovery while significantly reducing the amount of sample required and eliminating the need for additional sample handling. PMID- 26560997 TI - Asymmetrically Substituted and pi-Conjugated 2,2'-Bipyridine Derivatives: Synthesis, Spectroscopy, Computation, and Crystallography. AB - A new series of monosubstituted styryl- and bistyryl-2,2'-bipyridine luminophores (compounds 16-23) have been synthesized via Horner-Wadsworth-Emmons reaction involving a monophosphonate and donor aromatic aldehydes. In the title chromophores, the amino donors are varied between acyclic and cyclic while the alkoxy donors are varied in terms of their number and position. The absorption maxima of these chromophores shift predominantly due to intramolecular charge transfer (ICT) between different donor and acceptor moieties. The title donor acceptor molecules exhibit intense fluorescence in solution at room temperature, and their emissive behavior has been found to be highly sensitive to solvent polarity. The fluorescence spectra and quantum yields of all the chromophores were recorded in four different solvent media, and the chromophores 16, 17, 19, and 21 exhibit fluorescence in the solid state too. The influence of the nature and position of the donor functionalities in the conjugated backbone of the bipyridine moiety on the electronic absorption properties of the title chromophores (16-23) has been demonstrated, which has further been corroborated by DFT and TD-DFT computation both in gas phase and in solution phase. The crystal structure of compound 18 has been described as a representative member of the family (16-23). PMID- 26560995 TI - Fabrication of tissue-engineered vascular grafts with stem cells and stem cell derived vascular cells. AB - INTRODUCTION: Cardiovascular disease is the leading cause of mortality worldwide. Current surgical treatments for cardiovascular disease include vascular bypass grafting and replacement with autologous blood vessels or synthetic vascular grafts. However, there is a call for better alternative biological grafts. AREAS COVERED: Tissue-engineered vascular grafts (TEVGs) are promising novel alternatives to replace diseased vessels. However, obtaining enough functional and clinically usable vascular cells for fabrication of TEVGs remains a major challenge. New findings in adult stem cells and recent advances in pluripotent stem cells have opened a new avenue for stem cell-based vascular engineering. In this review, recent advances on stem cell sourcing for TEVGs including the use of adult stem cells and pluripotent stem cells and advantages, disadvantages, and possible future implementations of different types of stem cells will be discussed. In addition, current strategies used during the fabrication of TEVGs will be highlighted. EXPERT OPINION: The application of patient-specific TEVGs constructed with vascular cells derived from immune-compatible stem cells possesses huge clinical potential. Advances in lineage-specific differentiation approaches and innovative vascular engineering strategies will promote the vascular regeneration field from bench to bedside. PMID- 26560998 TI - A Helix-Stabilized Cell-Penetrating Peptide as an Intracellular Delivery Tool. AB - Two types of cationic cyclic alpha,alpha-disubstituted alpha-amino acids: ApiC2NH2 (which possesses a lysine mimic side chain) and Api(C2Gu) (which possesses an arginine mimic side chain), were developed. These amino acids were incorporated into an arginine-based peptide sequence [(L-Arg-L-Arg-dAA)3: dAA=ApiC2NH2 or Api(C2Gu)], and the relationship between the secondary structures of the resulting peptides and their ability to pass through cell membranes was investigated. The peptide containing Api(C2Gu) formed a stable alpha-helical structure and was more effective at penetrating cells than the nonhelical Arg nonapeptide (R9). Furthermore, the peptide was able to deliver plasmid DNA into various types of cells in a highly efficient manner. PMID- 26560996 TI - Developmental vitamin D deficiency and schizophrenia: the role of animal models. AB - Schizophrenia is a debilitating neuropsychiatric disorder that affects 1% of the US population. Based on twin and genome-wide association studies, it is clear that both genetics and environmental factors increase the risk for developing schizophrenia. Moreover, there is evidence that conditions in utero, either alone or in concert with genetic factors, may alter neurodevelopment and lead to an increased risk for schizophrenia. There has been progress in identifying genetic loci and environmental exposures that increase risk, but there are still considerable gaps in our knowledge. Furthermore, very little is known about the specific neurodevelopmental mechanisms upon which genetics and the environment act to increase disposition to developing schizophrenia in adulthood. Vitamin D deficiency during the perinatal period has been hypothesized to increase risk for schizophrenia in humans. The developmental vitamin D (DVD) deficiency hypothesis of schizophrenia arises from the observation that disease risk is increased in individuals who are born in winter or spring, live further from the equator or live in urban vs. rural settings. These environments result in less exposure to sunlight, thereby reducing the initial steps in the production of vitamin D. Rodent models have been developed to characterize the behavioral and developmental effects of DVD deficiency. This review focuses on these animal models and discusses the current knowledge of the role of DVD deficiency in altering behavior and neurobiology relevant to schizophrenia. PMID- 26560999 TI - Atroposelective Synthesis of Axially Chiral Biaryldiols via Organocatalytic Arylation of 2-Naphthols. AB - The first phosphoric acid-catalyzed asymmetric direct arylative reactions of 2 naphthols with quinone derivatives have been developed, providing efficient access to a class of axially chiral biaryldiols in good yields with excellent enantioselectivities under mild reaction conditions. This approach is a highly convergent and functional group tolerant route to the rapid construction of axially chiral compounds from simple, readily available starting materials. The excellent stereocontrol of the process stems from efficient transfer of stereochemical information from the chiral phosphoric acid into the axis chirality of the biaryldiol products. Preliminary results demonstrate that the biaryldiols can act as efficient chiral ligands in asymmetric transformations. PMID- 26561000 TI - Transcription factor-mediated reprograming of fibroblasts to hepatocyte-like cells. AB - Direct conversion by overexpression of defined transcription factors (TFs) is a promising new method that can generate desired cell types from abundant, accessible cells. While previous studies have reported hepatic generation from fibroblasts, tremendous interest exists in the understanding of hepatic reprograming and its applicability in regenerative medicine. Here, we show that overexpression of Yamanaka factors can induce reprograming of mouse fibroblasts into cells that closely resemble hepatocytes in vitro in the presence of an optimized hepatic growth medium. By screening the effects of 20 candidate transcription factors, we identified a combination of three TFs (Hnf4a, Cebpa, and Nr1i2) that can convert fibroblasts into a hepatic fate. These factors in conjunction with Yamanaka factors increase the efficiency of hepatic reprograming. The induced hepatocyte-like (iHep) cells have multiple hepatocyte specific characteristics; express hepatocyte-specific markers, glycogen storage, albumin secretion, urea production, as well as low-density lipoprotein and indocyanin green uptake. Production of iHep cells by these novel approaches may bring new insights into the molecular nature of hepatocyte differentiation and future cell-based therapeutics for liver diseases. PMID- 26561001 TI - Periodic Breathing in Heart Failure Explained by Dynamic and Static Properties of Respiratory Control. AB - OBJECTIVE: The respiratory operating point is determined by the interplay between the controller and plant subsystem elements within the respiratory chemoreflex feedback system. This study aimed to establish the methodological basis for quantitative analysis of the open-loop dynamic properties of the human respiratory control system and to apply the results to explore detailed mechanisms of the regulation of respiration and the possible mechanism of periodic breathing in chronic heart failure. METHODS AND RESULTS: In healthy volunteers, we measured arterial CO2 partial pressure (PaCO2) and minute ventilation [Formula: see text] to estimate the dynamic properties of the controller ( [Formula: see text] relation) and plant ( [Formula: see text] relation). The dynamic properties of the controller and plant approximated first- and second-order exponential models, respectively, and were described using parameters including gain, time constant, and lag time. We then used the open loop transfer functions to simulate the closed-loop respiratory response to an exogenous disturbance, while manipulating the parameter values to deviate from normal values but within physiological ranges. By increasing both the product of gains of the two subsystem elements (total loop gain) and the lag time, the condition of system oscillation (onset of periodic breathing) was satisfied. CONCLUSION: When abnormality occurs in a part of the respiratory chemoreflex system, instability of the control system is amplified and may result in the manifestation of respiratory abnormalities such as periodic breathing. PMID- 26561002 TI - Quantification of hepatic functional capacity: a call for standardization. AB - Reliable assessments of liver function are becoming increasingly important as more patients with surgically amenable liver disease are considered for treatment. Static markers of liver function are not sufficient to provide accurate assessments of hepatic function in order to risk stratify patients undergoing hepatic resection. Metabolic tests are dynamic indicators of liver function, but can be unreliable under certain conditions and thus difficult to make comparisons. Clearance tests avoid some of the pitfalls encountered during metabolic testing, but depend on hepatic blood flow and say little about hepatocyte function. Testing that combines imaging with measures of hepatocyte uptake may offer the most utility when planning surgical resections. PMID- 26561003 TI - Novel Hits in the Correction of DeltaF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-d]pyrimidines for the Potential Treatment of Cystic Fibrosis. AB - Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) with a prevalence of the DeltaF508 mutation. Whereas the detailed mechanisms underlying disease have yet to be fully elucidated, recent breakthroughs in clinical trials have demonstrated that CFTR dysfunction can be corrected by drug-like molecules. On the basis of this success, a screening campaign was carried out, seeking new drug-like compounds able to rescue DeltaF508-CFTR that led to the discovery of a novel series of correctors based on a tetrahydropyrido[4,3-d]pyrimidine core. These molecules proved to be soluble, cell-permeable, and active in a disease relevant functional-assay. The series was then further optimized with emphasis on biological data from multiple cell systems while keeping physicochemical properties under strict control. The pharmacological and ADME profile of this corrector series hold promise for the development of more efficacious compounds to be explored for therapeutic use in CF. PMID- 26561004 TI - Identifying and quantifying two ligand-binding sites while imaging native human membrane receptors by AFM. AB - A current challenge in life sciences is to image cell membrane receptors while characterizing their specific interactions with various ligands. Addressing this issue has been hampered by the lack of suitable nanoscopic methods. Here we address this challenge and introduce multifunctional high-resolution atomic force microscopy (AFM) to image human protease-activated receptors (PAR1) in the functionally important lipid membrane and to simultaneously localize and quantify their binding to two different ligands. Therefore, we introduce the surface chemistry to bifunctionalize AFM tips with the native receptor-activating peptide and a tris-N-nitrilotriacetic acid (tris-NTA) group binding to a His10-tag engineered to PAR1. We further introduce ways to discern between the binding of both ligands to different receptor sites while imaging native PAR1s. Surface chemistry and nanoscopic method are applicable to a range of biological systems in vitro and in vivo and to concurrently detect and localize multiple ligand binding sites at single receptor resolution. PMID- 26561005 TI - Addition to "Phosphoproteomic Analysis of Aurora Kinase Inhibition in Monopolar Cytokinesis". PMID- 26561006 TI - iSRAP - a one-touch research tool for rapid profiling of small RNA-seq data. AB - Small non-coding RNAs have been significantly recognized as the key modulators in many biological processes, and are emerging as promising biomarkers for several diseases. These RNA species are transcribed in cells and can be packaged in extracellular vesicles, which are small vesicles released from many biotypes, and are involved in intercellular communication. Currently, the advent of next generation sequencing (NGS) technology for high-throughput profiling has further advanced the biological insights of non-coding RNA on a genome-wide scale and has become the preferred approach for the discovery and quantification of non-coding RNA species. Despite the routine practice of NGS, the processing of large data sets poses difficulty for analysis before conducting downstream experiments. Often, the current analysis tools are designed for specific RNA species, such as microRNA, and are limited in flexibility for modifying parameters for optimization. An analysis tool that allows for maximum control of different software is essential for drawing concrete conclusions for differentially expressed transcripts. Here, we developed a one-touch integrated small RNA analysis pipeline (iSRAP) research tool that is composed of widely used tools for rapid profiling of small RNAs. The performance test of iSRAP using publicly and in-house available data sets shows its ability of comprehensive profiling of small RNAs of various classes, and analysis of differentially expressed small RNAs. iSRAP offers comprehensive analysis of small RNA sequencing data that leverage informed decisions on the downstream analyses of small RNA studies, including extracellular vesicles such as exosomes. PMID- 26561007 TI - Black tea: Phytochemicals, cancer chemoprevention, and clinical studies. AB - Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-kappaB, Bcl-xL, caspases, p53, FOXO1, TNFalpha, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect. PMID- 26561008 TI - Differential Large-Amplitude Breathing Motions in the Interface of FKBP12-Drug Complexes. AB - The tight complexes FKBP12 forms with immunosuppressive drugs, such as FK506 and rapamycin, are frequently used as models for developing approaches to structure based drug design. Although the interfaces between FKBP12 and these ligands are well-defined structurally and are almost identical in the X-ray crystallographic structures of various complexes, our nuclear magnetic resonance studies have revealed the existence of substantial large-amplitude motions in the FKBP12 ligand interfaces that depend on the nature of the ligand. We have monitored these motions by measuring the rates of Tyr and Phe aromatic ring flips, and hydroxyl proton exchange for residues clustered within the FKBP12-ligand interface. The results show that the rates of hydroxyl proton exchange and ring flipping for Tyr26 are much slower in the FK506 complex than in the rapamycin complex, whereas the rates of ring flipping for Phe48 and Phe99 are significantly faster in the FK506 complex than in the rapamycin complex. The apparent rate differences observed for the interfacial aromatic residues in the two complexes confirm that these dynamic processes occur without ligand dissociation. We tentatively attribute the differential interface dynamics for these complexes to a single hydrogen bond between the zeta-hydrogen of Phe46 and the C32 carbonyl oxygen of rapamycin, which is not present in the KF506 complex. This newly identified Phe46 zeta-hydrogen bond in the rapamycin complex imposes motional restriction on the surrounding hydrophobic cluster and subsequently regulates the dynamics within the protein-ligand interface. Such information concerning large amplitude dynamics at drug-target interfaces has the potential to provide novel clues for drug design. PMID- 26561009 TI - Patient dissatisfaction after total knee arthroplasty for hemophilic arthropathy and osteoarthritis (non-hemophilia patients). AB - In advanced painful hemophilic arthropathy of the knee (APHAK) and advanced painful osteoarthritis of the knee (APOAK) the last resort is total knee arthroplasty (TKA). However, some patients with APOAK are not satisfied despite a good clinical result. A review the literature on APHAK and APOAK was performed to know their rates of dissatisfaction and their main causes. In APOAK the rate of dissatisfaction ranges between 3 and 28.3%. Causes of dissatisfaction in APOAK are high preoperative body mass index, lack of fulfillment of patient expectations, a low 1-year WOMAC, preoperative pain at rest, a postoperative complication requiring hospital readmission, and a poor preoperative psychological state. Very limited information exists on APAHAK in the literature, but it also shows an increase in patient satisfaction after TKA. However, the results do not reach the same level as in patients with APOAK, due to residual symptoms and impairment of other joints. PMID- 26561010 TI - Spaceflight Effects on Cytochrome P450 Content in Mouse Liver. AB - Hard conditions of long-term manned spaceflight can affect functions of many biological systems including a system of drug metabolism. The cytochrome P450 (CYP) superfamily plays a key role in the drug metabolism. In this study we examined the hepatic content of some P450 isoforms in mice exposed to 30 days of space flight and microgravity. The CYP content was established by the mass spectrometric method of selected reaction monitoring (SRM). Significant changes in the CYP2C29, CYP2E1 and CYP1A2 contents were detected in mice of the flight group compared to the ground control group. Within seven days after landing and corresponding recovery period changes in the content of CYP2C29 and CYP1A2 returned to the control level, while the CYP2E1 level remained elevated. The induction of enzyme observed in the mice in the conditions of the spaceflight could lead to an accelerated biotransformation and change in efficiency of pharmacological agents, metabolizing by corresponding CYP isoforms. Such possibility of an individual pharmacological response to medication during long term spaceflights and early period of postflight adaptation should be taken into account in space medicine. PMID- 26561011 TI - Clinical relevance of single nucleotide polymorphisms within the 13 cytokine genes in North Indian trauma hemorrhagic shock patients. AB - INTRODUCTION: The susceptibility to adverse outcome from critical injury (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. We assessed the relationship of the genotype distribution of various cytokine gene polymorphisms (CGP) with regard to the development of sepsis, organ dysfunction or mortality in severely injured patients. METHOD: Observational, hospital-based cohort study of 114 severely injured North Indian patients from New Delhi admitted to the Emergency Department (ED) of Trauma Centre, AIIMS. Patients were monitored from day first to discharge or death, measuring SOFA score, sepsis and septic shock occurrences up to one month. We have analyzed 13 cytokine genes, including the SNPs of structural and regulatory regions at 22 positions. RESULTS: Sequence-specific primer based PCR indicated that eight polymorphic loci IL 1alpha /-889, IL-1beta/-511, IL-1R (pstI 1970), TGF-beta/ code 10, TNF-alpha/ 308, TNF-alpha/-238, IL-6/+565 and IL-10/-1082, out of 22 SNPs are significantly associated with sepsis morbidity and outcome. Theses SNPs might be used as risk determinants of the outcome. Patients with IL-10 (-1082A/A) genotypes were found significantly higher in post traumatic sepsis patients and had a significantly higher risk to developed sepsis complication (p < 0.05, OR = 0.86, C.I = 0.08 8.8).In case of TNF-alpha (-308) position, GA and GG genotype patients have a significantly lower risk of poor outcome (p < 0.05, OR = 0.25, C.I = 0.01-1.3) and (p < 0.05, OR = 0.22, C.I = 0.01-0.5) in comparison to AA genotype. In this study, two polymorphisms (IL-1beta (-511) and IL-1R) were significantly associated with the development of MOF and mortality, where as IL-1alpha (-889) polymorphism associated with susceptibility for sepsis. The distribution of haplotypes of TGF-beta and IL-6 were also associated with sepsis susceptibility and outcome. CONCLUSION: In conclusion, we have found that the alternations in the genotype and allele frequency of IL-1beta (-511C/T), TNF-alpha (-308 G/A), TNF-alpha (-238 G/A) and IL-10 (-1082 G/A) genes are associated with an higher risk of sepsis development in trauma patients and outcomes. PMID- 26561013 TI - Zoonotic ocular onchocercosis caused by Onchocerca lupi in dogs in Romania. AB - Onchocerca lupi is a filarial nematode, which infects the scleral conjunctival tissue of dogs, wolves and cats. Whilst adult nematodes localize in the conjunctive tissue of sclera or in the retrobulbar, microfilariae are found in the skin, and they are rarely diagnosed in asymptomatic animals. Since the first report of human ocular infection 5 years ago, up to 10 zoonotic cases have been identified in patients worldwide. We report, for the first time in Romania, three cases of canine ocular onchocercosis in dogs. Fragments of the harvested worms were characterized morphologically and molecularly. This article expands knowledge on the distribution of this parasite in Eastern Europe and sounds an alarm bell for ophthalmologists about the possible occurrence of human cases of O. lupi infection. PMID- 26561012 TI - Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture. AB - The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 +/- 1.8 to 35.9 +/- 5.5 kg/m2 (mean +/- 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity. PMID- 26561014 TI - An overview of investigational new drugs for treating ankylosing spondylitis. AB - INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic condition. Pharmacological treatment relies on nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (in case of peripheral involvement) and anti-TNF agents in case of inadequate response. To date, there are no alternate options, and about 30% of the patients do not adequately respond to anti-TNF therapy. AREAS COVERED: This overview is based on recent publications and programmed studies. The author provides the reader with an overview of AS, its current management and provide details of novel insights into the disorder. From there, the authors highlight novel treatments under investigation before providing their expert opinion on the field. EXPERT OPINION: The first results with biodrugs targeting the IL-23/Th17 pathway are encouraging, and secukinumab will likely be available in the forthcoming years to treat AS. Other targets may be evaluated in this axis. The author believes that additional head-to-head studies are needed find the place of these new drugs in AS treatment strategies. Further studies are also needed to better evaluate their long-term outcome and safety. PMID- 26561015 TI - Giant prolactinomas: are they really different from ordinary macroprolactinomas? AB - Giant prolactinomas (gPRLomas) are rare tumors of the lactotroph defined by an unusually large size (>4 cm) and serum PRL levels >1000 ng/mL. The purpose of this study is to characterize the clinical spectrum of gPRLomas comparing them with non-giant prolactinomas. This is a retrospective study at a large referral center. Data from patients harboring gPRLomas and macroprolactinomas were retrieved from medical records of the Prolactinoma Clinic. Analysis was focused on clinical, biochemical, and tumor volume characteristics, as well as on the response to treatment with dopamine agonists. Among 292 patients with prolactinomas followed between 2008 and 2015, 47 (16 %) met the diagnostic criteria for gPRLomas (42 males). The most common complaint was a visual field defect; headache was reported by 79 % and sexual dysfunction was present in over half of the patients. Median basal PRL level and tumor volume were 6667 ng/mL (3750-10,000) and 32 cm(3) (20-50), respectively; hypogonadotropic hypogonadism was documented in 87 %. Cabergoline treatment resulted in the normalization of PRL levels in 68 % and in the reduction of >50 % in tumor volume in 87 % of the gPRLoma patients. The composite goal of PRL normalization and >50 % tumor reduction was achieved by 55 % (n = 26) of patients with gPRL and by 66 % (n = 100) of patients with no giant macroprolactinomas (p = 0.19). Recovery of hypogonadism and improvement of visual fields defects occurred in 32 % and 68 % of the patients, respectively. Cabergoline treatment was equally effective in patients with gPRLoma and those with macroprolactinomas in regard of achieving treatment goals, although the median CBG dose was slightly higher in the gPRLoma group (2 vs. 1.5 mg/w). Six patients required surgery. Beyond their impressive dimensions and the huge amount of PRL they secrete, the clinical behavior of gPRLoma is not different from macroprolactinomas. These tumors are highly responsive to cabergoline treatment, and pituitary surgery is seldom required. PMID- 26561016 TI - Understanding the virulence of the entero-aggregative E. coli O104:H4. AB - O104:H4 is a new strain of E. coli that has caused an outbreak in Germany. It was isolated from patients with bloody diarrhoea and Haemolytic Uremic Syndrome (HUS). BGI (www.genomics.cn) sequenced and assembled this new strain. It was reported to show resistance to a number of drugs that are toxic to other E. coli and causes serious complications during infections, which ultimately lead to death. Multi-drug resistance and high virulence of this strain is thought to be acquired from different sources, by horizontal gene transfer. A total of 38 prophage elements were detected from the new strain by using three computational tools viz., DRAD, Prophage Finder and PHAST. Analysis on these prophage elements shows a number of virulence proteins like Shiga toxin and multi-drug resistance protein encoding genes. The high virulence of the strain could be attributed by the prophage elements acquired from its micro environment. PMID- 26561017 TI - Predicting DNA mutations during cancer evolution. AB - Bio-systems are inherently complex information processing systems. Their physiological complexities limit the formulation and testing of a hypothesis for their behaviour. Our goal here was to test a computational framework utilising published data from a longitudinal study of patients with acute myeloid leukaemia (AML), whose DNA from both normal and malignant tissues were subjected to NGS analysis at various points in time. By processing the sequencing data before relapse time, we tested our framework by predicting the regions of the genome to be mutated at relapse time and, later, by comparing our results with the actual regions that showed mutations (discovered by genome sequencing at relapse time). After a detailed statistical analysis, the resulting correlation coefficient (degree of matching of proposed framework with real data) is 0.9816 +/- 0.009 at 95% confidence interval. This high performance from our proposed framework opens new research opportunities for bioinformatics researchers and clinical doctors. PMID- 26561018 TI - Mining amino acid association patterns in class B GPCRs. AB - Class B GPCR family is a small group of receptors which are activated by peptides of intermediate length that range from 30 to 40 amino acid residues including hormones, neuropeptides and autocrine factors that mediate diverse physiological functions. They are involved in physiological processes like glucose homeostasis (glucagon and glucagon-like peptide-1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Most of the GPCR structures and their functions are still unknown. Thus, the study of amino acid association patterns can be useful in prediction of their structure and functions. In view of above, in this paper, an attempt has been made to explore amino acid association patterns in class B GPCRs and their relationships with secondary structures and physiochemical properties. The fuzzy association rule mining is employed to take care of uncertainty due to variation in length of sequences. The association rules have been generated with the help of patterns discovered in the sequences. PMID- 26561019 TI - Mining nutrigenetics patterns related to obesity: use of parallel multifactor dimensionality reduction. AB - This paper aims to enlighten the complex etiology beneath obesity by analysing data from a large nutrigenetics study, in which nutritional and genetic factors associated with obesity were recorded for around two thousand individuals. In our previous work, these data have been analysed using artificial neural network methods, which identified optimised subsets of factors to predict one's obesity status. These methods did not reveal though how the selected factors interact with each other in the obtained predictive models. For that reason, parallel Multifactor Dimensionality Reduction (pMDR) was used here to further analyse the pre-selected subsets of nutrigenetic factors. Within pMDR, predictive models using up to eight factors were constructed, further reducing the input dimensionality, while rules describing the interactive effects of the selected factors were derived. In this way, it was possible to identify specific genetic variations and their interactive effects with particular nutritional factors, which are now under further study. PMID- 26561020 TI - BioInt: an integrative biological object-oriented application framework and interpreter. AB - BioInt, a biological programming application framework and interpreter, is an attempt to equip the researchers with seamless integration, efficient extraction and effortless analysis of the data from various biological databases and algorithms. Based on the type of biological data, algorithms and related functionalities, a biology-specific framework was developed which has nine modules. The modules are a compilation of numerous reusable BioADTs. This software ecosystem containing more than 450 biological objects underneath the interpreter makes it flexible, integrative and comprehensive. Similar to Python, BioInt eliminates the compilation and linking steps cutting the time significantly. The researcher can write the scripts using available BioADTs (following C++ syntax) and execute them interactively or use as a command line application. It has features that enable automation, extension of the framework with new/external BioADTs/libraries and deployment of complex work flows. PMID- 26561021 TI - Impact of pixel intensity correlations on statistical inferences of expression levels in cDNA microarray experiments. AB - In a cDNA microarray experiment, the final measurement is intensity ratio at a spot in the microarray chip. The objective of the present study is to estimate the uncertainty associated with the final intensity ratio at each spot in cDNA microarray chips and also to explore the role of pixel intensity correlations in statistical inferences of gene expression levels. We estimate uncertainty at each spot using the theory of error propagation under two different situations: (1) when there is no correlation between pixel intensities and (2) when the pixel intensities are positively correlated. The inverses of these estimated uncertainties are used as weights in downstream analysis to test the significance of each gene. The analysis was verified on a data downloaded from the GEO database. Our study shows that the uncertainty and statistical inference of gene expression levels depend on correlation between pixel intensities within a spot. PMID- 26561022 TI - Analysing extremely small sized ratio datasets. AB - The naive use of expression ratios in high-throughput biological studies can greatly limit analytical outcome especially when sample size is small. In the worst-case scenario, with only one reference and one test state each (often due to the severe lack of study material); such limitations make it difficult to perform statistically meaningful analysis. Workarounds include the single sample Z-test or through network inference. Here, we describe a complementary plot-based approach for analysing such extremely small sized ratio (ESSR) data - a generalisation of the Bland-Altman plot, which we shall refer to as the Dodeca Panels. Included in this paper is an R implementation of the Dodeca-Panels method. PMID- 26561023 TI - Care delivery and outcomes among US veterans with hepatitis B: A national cohort study. AB - Previous studies have identified gaps in hepatitis B care. The objectives of this study were to evaluate the delivery of care among a national cohort of US veterans with chronic hepatitis B infection and examine risk factors for adverse clinical outcomes. We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse from 1999 to 2013 to evaluate (1) care delivery and (2) clinical outcomes such as hepatocellular carcinoma, hepatic decompensation, and mortality among US veterans with hepatitis B. Incidence rates with 95% confidence intervals were calculated and Cox regression models were used to evaluate clinical outcomes. We identified 21,419 veterans with a positive hepatitis B surface antigen, and 97% of patients had alanine aminotransferase and 44% had hepatitis B virus DNA testing; hepatitis B e antigen and hepatitis B e antibody were tested <50% of the time. Patients receiving specialty care had a higher prevalence of recommended laboratory testing. Patients with elevated alanine aminotransferase in specialty care were more likely to receive antiviral therapy (50% versus 24% for specialty care versus no specialty care, P < 0.001). Among patients with cirrhosis, 69% received one-time liver imaging. The proportion of follow-up time adherent to annual imaging was 0.39 (standard deviation = 0.42), and the proportion was 0.28 (standard deviation = 0.33) for biannual imaging; both proportions were higher in the specialty care group (all P < 0.05). Antiviral therapy (hazard ratio = 0.85, 95% confidence interval 0.76 0.95, P = 0.005) and liver imaging (hazard ratio = 0.84, 95% confidence interval 0.76-0.91, P < 0.001) were independently associated with decreased mortality in adjusted analyses. CONCLUSION: We observed a low prevalence of recommended laboratory testing, antiviral therapy initiation, and liver imaging among a national cohort of veterans with hepatitis B infection; antiviral therapy and liver imaging were independently associated with decreased mortality. (Hepatology 2016;63:1774-1782). PMID- 26561024 TI - [Research applications in digital radiology. Big data and co]. AB - Medical imaging produces increasingly complex images (e.g. thinner slices and higher resolution) with more protocols, so that image reading has also become much more complex. More information needs to be processed and usually the number of radiologists available for these tasks has not increased to the same extent. The objective of this article is to present current research results from projects on the use of image data for clinical decision support. An infrastructure that can allow large volumes of data to be accessed is presented. In this way the best performing tools can be identified without the medical data having to leave secure servers. The text presents the results of the VISCERAL and Khresmoi EU-funded projects, which allow the analysis of previous cases from institutional archives to support decision-making and for process automation. The results also represent a secure evaluation environment for medical image analysis. This allows the use of data extracted from past cases to solve information needs occurring when diagnosing new cases. The presented research prototypes allow direct extraction of knowledge from the visual data of the images and to use this for decision support or process automation. Real clinical use has not been tested but several subjective user tests showed the effectiveness and efficiency of the process. The future in radiology will clearly depend on better use of the important knowledge in clinical image archives to automate processes and aid decision-making via big data analysis. This can help concentrate the work of radiologists towards the most important parts of diagnostics. PMID- 26561025 TI - [Modern MRI of the small bowell]. AB - CLINICAL METHODOLOGICAL ISSUES: The radiological diagnostics of diseases of the small intestine have undergone a great change in the last two decades. Through rapid progress with new treatments and an increasing therapeutic focus on transmural healing, a complete evaluation of the gastrointestinal tract is now crucial. STANDARD RADIOLOGICAL METHODS: With the introduction of endoscopy, gastrointestinal imaging with a relatively high radiation exposure had only limited applications. The development of cross-sectional imaging allowed a much broader radiological evaluation of abdominal diseases. Due to rapid investigation techniques, excellent soft tissue contrast and the distinct advantage of eliminating exposure to radiation, magnetic resonance imaging (MRI) of the gastrointestinal tract has gained increasing importance. With sufficient filling of the intestinal lumen, simultaneous imaging of all the intestinal wall layers, the perienteric structures and associated abdominal pathologies is now possible. METHODOLOGICAL INNOVATIONS: New MR sequences, such as diffusion-weighted sequences, dynamic contrast-enhanced sequences and MR fluoroscopy, enable the detection of morphological changes, with additional characterization of affected bowel loops as well as the assessment of functional pathologies with dynamic information about intestinal motility disturbances. ACHIEVEMENTS: Recent guidelines of European radiological and gastroenterological organizations have confirmed the importance of cross-sectional imaging and particularly of MRI for diagnostics and follow-up in patients with Crohn's disease. Due to the possibility of assessment of all the layers of the intestinal wall and the presence of extramural complications, MRI has a significant impact on further therapeutic treatment in patients with inflammatory bowel disease. PRACTICAL RECOMMENDATIONS: Especially in patients with inflammatory bowel disease, MR enterography and MR enteroclysis should be the methods of choice for the evaluation of small bowel pathologies because of radiation issues and the great diagnostic value they provide. A variety of MR sequences has enabled not only the detection but also the characterization of pathological changes of the small intestine, which are vital for further treatment of these patients. PMID- 26561026 TI - [Spinal cord displacement with progressive paraplegia]. PMID- 26561027 TI - When Anthropogenic River Disturbance Decreases Hybridisation between Non-Native and Endemic Cyprinids and Drives an Ecomorphological Displacement towards Juvenile State in Both Species. AB - Understanding the impact of non-native species on native species is a major challenge in molecular ecology, particularly for genetically compatible fish species. Invasions are generally difficult to study because their effects may be confused with those of environmental or human disturbances. Colonized ecosystems are differently impacted by human activities, resulting in diverse responses and interactions between native and non-native species. We studied the dynamics between two Cyprinids species (invasive Chondrostoma nasus and endemic Parachondrostoma toxostoma) and their hybrids in 16 populations (from allopatric to sympatric situations and from little to highly fragmented areas) corresponding to 2,256 specimens. Each specimen was assigned to a particular species or to a hybrid pool using molecular identification (cytochrome b and 41 microsatellites). We carried out an ecomorphological analysis based on size, age, body shape, and diet (gut vacuity and molecular fecal contents). Our results contradicted our initial assumptions on the pattern of invasion and the rate of introgression. There was no sign of underperformance for the endemic species in areas where hybridisation occurred. In the unfragmented zone, the introduced species was found mostly downstream, with body shapes similar to those in allopatric populations while both species were found to be more insectivorous than the reference populations. However, high level of hybridisation was detected, suggesting interactions between the two species during spawning and/or the existence of hybrid swarm. In the disturbed zone, introgression was less frequent and slender body shape was associated with diatomivorous behaviour, smaller size (juvenile characteristics) and greater gut vacuity. Results suggested that habitat degradation induced similar ecomorphological trait changes in the two species and their hybrids (i.e. a transition towards a pedomorphic state) where the invasive species is more affected than the native species. Therefore, this study reveals a diversity of relationships between two genetically compatible species and emphasizes constraints on the invasion process in disturbed areas. PMID- 26561028 TI - In Vivo Evaluation of a Bombesin Analogue Labeled with Ga-68 and Co-55/57. AB - PURPOSE: The purpose of this study was to apply an analogue of bombesin, NOTA AMBA, labeled with Co-55 or Ga-68, for preclinical imaging of prostate cancer. PROCEDURES: The peptide NOTA-AMBA was labeled with Ga-68 or Co-55 by microwave irradiation. Biodistribution in xenograft mice (PC3) was performed at 1, 4, and 24 h (only cobalt at 24 h) using a fixed amount of peptide. Four weeks post inoculation, xenograft mice were positron emission tomography/X-ray computed tomography scanned after tail vein injection of [(68)Ga]NOTA-AMBA or [(55)Co]NOTA AMBA. RESULTS: Labeling with Ga-68 and Co-55/57 was achieved in yields greater than 90 %. A radiochemical purity (RCP) of 95 and 90 % were obtained for Ga-68 and Co-55, respectively. Both radiopeptides showed high uptake in the intestines, stomach, pancreas, and in the tumor ([(68)Ga]NOTA-AMBA, 10.3 %ID/g at 1 h to 6.4 %ID/g at 4 h; [(57)Co]NOTA-AMBA, 8.2 %ID/g at 1 h to 5.3%ID/g at 24 h). Normal tissue cleared over time improving tumor-to-background ratios. CONCLUSIONS: NOTA AMBA was labeled in high yields and RCP with Ga-68 and Co-55/57. High tumor uptake in a subcutaneous mouse prostate cancer model was observed. At 24 h, [(55/57)Co]NOTA-AMBA showed better tumor-to-organ ratios than [(68)Ga]NOTA-AMBA at both 1 and 4 h post-injection. Hence, for imaging, [(55)Co]NOTA-AMBA was found to be superior compared to [(68)Ga]NOTA-AMBA. PMID- 26561029 TI - Parental knowledge, attitudes and practices regarding antibiotic use for acute upper respiratory tract infections in children: a cross-sectional study in Palestine. AB - BACKGROUND: In primary health care centres, upper respiratory tract infections (URTIs) in children are commonly encountered by physicians. Viruses cause most URTIs, but parents' attitudes often represent an important reason for antibiotic abuse, which leads to the development and spread of antimicrobial resistance. The goal of this study was to examine parents' knowledge, attitudes, and practices (KAP) about antibiotic use for children with URTIs in Palestine. METHODS: A cross sectional study was performed in primary health care centres in Nablus city from 1 June to 31 October 2012. A questionnaire was developed and administered to determine parents' KAP regarding antibiotic use for their children with URTIs. RESULTS: Three hundred and eighty-five parents completed the questionnaire. A total of 79.7% of the parents were attentive to the truth that antibiotic misuse is responsible for bacterial resistance. Only 18.9% of parents thought that antibiotics did not have any harmful side effects. Fifty nine per cent of parents did not agree that URTIs are mostly viral in origin and are self-limited. Almost 73% of parents choose antibiotics as a treatment for URTIs, while earache (68%) and fever (64%) were the most common reasons for which parents expected antibiotics. However, more than 38% of the parents never asked the paediatrician to prescribe antibiotics, and only 6% congratulated their paediatricians for not prescribing antibiotics. CONCLUSIONS: Although there is a trusted relationship between parents and paediatricians, Palestinian parents have insufficient knowledge related to antibiotic use for URTIs in children, which results in inappropriate attitudes and practices. Educational interventions for both parents and physicians will reduce unnecessary antibiotic use and resistance. PMID- 26561030 TI - Allergic airway inflammation: unravelling the relationship between IL-37, IL 18Ralpha and Tir8/SIGIRR. AB - The hallmarks of allergic bronchial asthma arise from chronic airway inflammation. Thus, elucidating the mechanisms regulating the maintenance of this chronic inflammatory response is key to understanding asthma pathogenesis. To date, it is not clear whether a predominance of proinflammatory factors or a reduced capacity of counterbalancing anti-inflammatory mediators is the pivotal factor predisposing individuals towards asthma development. The IL-1 cytokine family and its receptor systems comprise a variety of proinflammatory cytokines like IL-1beta and IL-18 and anti-inflammatory molecules such as the Toll/interleukin-1 receptor 8/single Ig IL-1 receptor (IL-R)-related molecule (Tir8/SIGIRR) and the recently established cytokine IL-37. This article reviews the functions of these IL-1 cytokine family members in the regulation of allergic airway inflammation and asthma as they have been assessed clinically, in vitro and in mouse models. PMID- 26561031 TI - Midterm functional results of taTME with neuromapping for low rectal cancer. AB - BACKGROUND: Information on functional outcomes after laparoscopic-assisted transanal total mesorectal excision (taTME) is limited. This study analyzed the functional results in patients with low rectal cancer. METHODS: Ten consecutive patients (nine males) undergoing electrophysiologically controlled nerve-sparing taTME were investigated prospectively and asked to complete functional questionnaires [the International Prostate Symptom Score (IPSS), International Index of Erectile Function, Female Sexual Function Index, Wexner score, and low anterior resection syndrome (LARS) score]. Bladder function was also assessed according to residual urine volume. Preoperative function was compared to the functional outcome 3 and 6 months, and 9 months if eligible, after stoma closure or surgery in the absence of a diverting stoma. RESULTS: Prior to therapy, urinary and sexual function was impaired in 40 and 60% of patients, respectively. None of the patients developed pathological residual urine volumes after at least unilateral functional pelvic nerve-sparing. Median IPSS was lower than preoperative scores (p > 0.05). Two males with incomplete nerve preservation were considered impotent during a median follow-up of 15 months (range 6-20 months). The female was judged to be sexually inactive. The median Wexner score was 1 (range 0-7) prior to any therapy and increased to 7 (range 0-15) at 6 months (p = 0.029), with 40% of patients categorized as having no LARS and 50% minor LARS. The median LARS score was 28 (range 9-38) at 3 months and 26 (range 9-32) at 6 months (p = 0.165). CONCLUSIONS: Despite a small sample size and confounding factors, data indicate that taTME has the potential to preserve continence, sufficient bowel function, and urogenital function. PMID- 26561032 TI - Depression and Mood Disorder Among African American and White Women. PMID- 26561033 TI - Computerised self help for depression in primary care. PMID- 26561034 TI - Palladium(0)/NHC-Catalyzed Reductive Heck Reaction of Enones: A Detailed Mechanistic Study. AB - We have studied the mechanism of the palladium-catalyzed reductive Heck reaction of para-substituted enones with 4-iodoanisole by using N,N-diisopropylethylamine (DIPEA) as the reductant. Kinetic studies and in situ spectroscopic analysis have provided a detailed insight into the reaction. Progress kinetic analysis demonstrated that neither catalyst decomposition nor product inhibition occurred during the catalysis. The reaction is first order in the palladium and aryl iodide, and zero order in the activated alkene, N-heterocyclic carbene (NHC) ligand, and DIPEA. The experiments with deuterated solvent ([D7]DMF) and deuterated base ([D15]Et3N) supported the role of the amine as a reductant in the reaction. The palladium complex [Pd(0)(NHC)(1)] has been identified as the resting state. The kinetic experiments by stopped-flow UV/Vis also revealed that the presence of the second substrate, benzylideneacetone 1, slows down the oxidative addition of 4-iodoanisole through its competing coordination to the palladium center. The kinetic and mechanistic studies indicated that the oxidative addition of the aryl iodide is the rate-determining step. Various scenarios for the oxidative addition step have been analyzed by using DFT calculations (bp86/def2-TZVP) that supported the inhibiting effect of substrate 1 by formation of resting state [Pd(0)(NHC)(1)] species at the cost of further increase in the energy barrier of the oxidative addition step. PMID- 26561035 TI - Copy number variation in CEP57L1 predisposes to congenital absence of bilateral ACL and PCL ligaments. AB - BACKGROUND: Absence of the anterior (ACL) or posterior cruciate ligament (PCL) are rare congenital malformations that result in knee joint instability, with a prevalence of 1.7 per 100,000 live births and can be associated with other lower limb abnormalities such as ACL agnesia and absence of the menisci of the knee. While a few cases of absence of ACL/PCL are reported in the literature, a number of large familial case series of related conditions such as ACL agnesia suggest a potential underlying monogenic etiology. We performed whole exome sequencing of a family with two individuals affected by ACL/PCL. RESULTS: We identified copy number variation (CNV) deletion impacting the exon sequences of CEP57L1, present in the affected mother and her affected daughter based on the exome sequencing data. The deletion was validated using quantitative PCR (qPCR), and the gene was confirmed to be expressed in ACL ligament tissue. Interestingly, we detected reduced expression of CEP57L1 in Epstein-Barr virus (EBV) cells from the two patients in comparison with healthy controls. Evaluation of 3D protein structure showed that the helix-binding sites of the protein remain intact with the deletion, but other functional binding sites related to microtubule attachment are missing. The specificity of the CNV deletion was confirmed by showing that it was absent in ~700 exome sequencing samples as well as in the database of genomic variations (DGV), a database containing large numbers of annotated CNVs from previous scientific reports. CONCLUSIONS: We identified a novel CNV deletion that was inherited through an autosomal dominant transmission from an affected mother to her affected daughter, both of whom suffered from the absence of the anterior and posterior cruciate ligaments of the knees. PMID- 26561036 TI - Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex. AB - A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death. PMID- 26561037 TI - Interventions for metabolic bone disease in children with chronic kidney disease. AB - BACKGROUND: Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010. OBJECTIVES: This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D. DATA COLLECTION AND ANALYSIS: Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model. MAIN RESULTS: This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI 32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active vitamin D preparations (calcitriol, paricalcitol, 1alpha-hydroxyvitamin D) with placebo or no specific treatment. One study reported vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI 0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV) calcitriol administration. Two studies (97 children) compared calcitriol with other vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared ergocalciferol in patients with CKD and vitamin D deficiency. Elevated PTH levels developed significantly later in ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared calcium carbonate with aluminium hydroxide as phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared sevelamer with calcium-containing phosphate binders. There were no significant differences in the final calcium, phosphorus or PTH levels between binders. More episodes of hypercalcaemia occurred with calcium-containing binders. One study reported no significant differences between calcitriol and doxercalciferol in bone histology or biochemical parameters. AUTHORS' CONCLUSIONS: Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However, no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations were demonstrated. Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All studies were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD. PMID- 26561038 TI - Widespread Environmental Contamination with Mycobacterium tuberculosis Complex Revealed by a Molecular Detection Protocol. AB - Environmental contamination with Mycobacterium tuberculosis complex (MTC) has been considered crucial for bovine tuberculosis persistence in multi-host pathogen systems. However, MTC contamination has been difficult to detect due to methodological issues. In an attempt to overcome this limitation we developed an improved protocol for the detection of MTC DNA. MTC DNA concentration was estimated by the Most Probable Number (MPN) method. Making use of this protocol we showed that MTC contamination is widespread in different types of environmental samples from the Iberian Peninsula, which supports indirect transmission as a contributing mechanism for the maintenance of bovine tuberculosis in this multi-host-pathogen system. The proportion of MTC DNA positive samples was higher in the bovine tuberculosis-infected than in presumed negative area (0.32 and 0.18, respectively). Detection varied with the type of environmental sample and was more frequent in sediment from dams and less frequent in water also from dams (0.22 and 0.05, respectively). The proportion of MTC-positive samples was significantly higher in spring (p<0.001), but MTC DNA concentration per sample was higher in autumn and lower in summer. The average MTC DNA concentration in positive samples was 0.82 MPN/g (CI95 0.70-0.98 MPN/g). We were further able to amplify a DNA sequence specific of Mycobacterium bovis/caprae in 4 environmental samples from the bTB-infected area. PMID- 26561039 TI - Phylogenetic Analysis Using the 28S rRNA Gene Reveals That the Genus Paracreptotrema (Digenea: Allocreadiidae) Is Not Monophyletic; Description of Two New Genera and One New Species. AB - This study investigates the systematics of Paracreptotrema Choudhury, Perez-Ponce de Leon, Brooks and Daverdin, 2006 using morphological data (stained whole mounts and scanning electron microscopy) and partial sequences of the 28S ribosomal rRNA gene, obtained from freshly collected material. In total, 484 specimens representing 4 species, i.e., Paracreptotrema blancoi (157), Paracreptotrema profundulusi (12), Paracreptotrema rosenthali (8), and Paracreptotrema blancoi sensu Salgado-Maldonado et al. (2011) (307) were collected. Existing museum depositions were also studied. The 28S rRNA gene sequences of these Paracreptotrema spp. were aligned, along with sequences from 22 other allocreadiids and 4 other non-allocreadiid xiphidiatan species. Bayesian inference and maximum likelihood analyses indicated a paraphyletic Paracreptotrema split into 3 clades: 1 comprising P. blancoi and P. rosenthali that was sister to a clade formed by 3 other species of allocreadiids (species of Wallinia, Creptotrematina, and Auriculostoma) typically found in characid fishes, a second clade formed solely by Paracreptotrema heterandriae as the sister taxon of the aforementioned species, and a third by P. profundulusi and specimens erroneously identified as P. blancoi. Two new taxa were erected to reflect these results: Paracreptotrematoides for Paracreptotrema heterandriae, and Pseudoparacreptotrema for Paracreptotrema profundulusi and P. macroacetabulata (the species erroneously identified as P. blancoi from profundulids across Middle America). Closer consideration of the morphology corroborates these findings. The revised systematics also indicated that Paracreptotrema spp. are found in poeciliids, whereas Pseudoparacreptotrema spp. parasitize profundulids. The study demonstrates the value of an integrative taxonomy approach to address the apparently complicated systematics of the allocreadiids. PMID- 26561040 TI - Emerging innovations in clinical trial design. AB - Designs of clinical trials have changed little since the advent of randomization in the 1940s. Modern innovations in designs are being driven by the increasing recognition in clinical research that diseases are heterogeneous and patients who apparently have the same disease require different therapies. This article describes some innovations in clinical trial design across therapeutic areas but with a focus on oncology. No one knows what the future holds for clinical trial design but the status quo of large trials that pretend the patient population is homogeneous is not sustainable, either economically or scientifically/medically. No one knows what the eventual business model and regulatory model will be, but they will be very different from today's. PMID- 26561041 TI - Definitive proton radiation therapy and concurrent cisplatin for unresectable head and neck adenoid cystic carcinoma: A series of 9 cases and a critical review of the literature. AB - BACKGROUND: The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACC's propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum-based chemotherapy. METHODS: Nine patients with unresectable node-negative, nonmetastatic head and neck ACC received definitive proton RT and concurrent cisplatin. Outcomes and toxicities were recorded. A systematic review of the literature was performed. RESULTS: Median follow-up was 27 months (range, 9.2 48.3 months). Four patients achieved complete response at the primary site, and an additional 4 patients achieved stabilization of local disease. Only 1 patient developed local disease progression. Four patients had 5 acute grade 3 (G3) toxicities, and 1 patient developed a chronic G4 optic nerve disorder. CONCLUSION: Our preliminary results suggest proton RT and concurrent chemotherapy is a definitive treatment option for select patients with head and neck ACC. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1472-E1480, 2016. PMID- 26561042 TI - Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region. AB - INTRODUCTION: The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. AIM: This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. METHODS: We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. RESULTS: Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). CONCLUSION: Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. PMID- 26561043 TI - Intense Imagery Movements (IIM): More to motor stereotypies than meets the eye. AB - AIM: A subgroup of children who present with motor stereotypies in the context of episodes of intense imagery have recently been described in the literature,(1) termed Intense Imagery Movements (IIM). All children report conscious engagement in acts of imagery or imagination, with stereotyped movements occurring simultaneously with limited conscious awareness. This article reports preliminary cognitive data to inform clinical management and guide future research. METHOD: Intellectual functioning was assessed for ten children with IIM (7 boys, 3 girls; mean age = 10;01, age range = 6;06 to 14;04). In-depth neuropsychological assessments were conducted for four of these cases (3 boys, 1 girls; mean age = 9;05), with standardised questionnaires completed to assess mood, behaviour, attention/concentration, sensory functioning, motor functioning and stereotyped movements. RESULTS: All children exhibited discrepant intellectual profiles, especially on perceptual reasoning tasks, with significant impairments in processing speed. In-depth neuropsychological assessments indicated impaired performance on tests of attention and inhibition, but strengths in memory or oral expression. Three of the four children had sensory processing impairments, two had features of developmental co-ordination disorder and one had poor general well-being. None of the children had emotional or behavioural problems. INTERPRETATION: Children with IIM exhibit uneven intellectual and cognitive profiles, with particular discrepancies in perceptual reasoning skills. The case studies suggest that weaker attention, inhibition and processing speed skills may contribute to engagement in IIM, with good memory and/or language skills potentially contributing to the complexity of imagery abilities. Implications for the identification and management of these children in clinical practice, and future research ideas, are discussed. PMID- 26561044 TI - Outcome of Hodgkin Lymphoma Patients With a Posttreatment 18F-Fluoro-2-Deoxy-d Glucose Positron Emission Tomography (FDG-PET)-Negative Residual Mass: Systematic Review and Meta-analysis. AB - To systematically review and meta-analyze the outcome of Hodgkin lymphoma patients with a posttreatment (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET)-negative residual mass. A systematic PubMed/MEDLINE database search was performed. The methodological quality of included studies was assessed. The number of patients with a posttreatment non-FDG-avid residual mass and the number of these patients who developed disease relapse during follow-up were extracted from each included study. Heterogeneity in disease relapse proportions across individual studies was assessed using the I2 test, with heterogeneity defined as I(2) > 50%. Using a Freeman-Tukey transformation, the disease relapse proportions from each individual study were then meta-analyzed with either a fixed-effects model (if I2 <= 50 %) or a random-effects model (if I2 > 50 %). A total of 5 studies comprising a total of 727 Hodgkin lymphoma patients with an FDG-PET-negative residual mass after first-line therapy were included. The overall quality of included studies was moderate. The proportion of patients with a posttreatment non-FDG-avid residual mass who experienced disease relapse during follow-up ranged between 0% and 13.8%. There was heterogeneity in disease relapse proportions across individual studies (I2 = 61.4%). Pooled disease relapse proportion (random effects) was 6.8% (95% confidence interval: 2.6%-12.5%). The disease relapse rate in Hodgkin lymphoma patients with a FDG-PET negative residual mass after first-line therapy is approximately 6.8%. Considering the existing literature, the presence of a non-FDG-avid residual mass has not been proven yet to be associated with a worse outcome than a posttreatment FDG-PET-based complete remission status without a residual mass. PMID- 26561045 TI - Pollinators and Other Flying Insects inside and outside the Fukushima Evacuation Zone. AB - Following the accident at the Fukushima Daiichi nuclear power plants in 2011, a large evacuation zone was imposed in an area where residents had historically managed forests and farmlands. Thus, the human activities that had maintained biodiversity and ecosystem services in the zone were discontinued. Such change can affect insects, a biodiversity component that is relatively tolerant to radiation exposure. In this study, we investigated flying insects, including pollinators, important ecosystem providers inside and outside the zone, using Malaise traps. The results showed that the number of individuals of Xylocopa appendiculata, the largest Apidae species in the region, was significantly lower inside the evacuation zone than outside it, whereas those of other insects were not lower significantly. Although we suggest that flying insects and their ecosystem services (i.e., benefits from them such as pollination) 3 years after the disaster were not critically impacted, it is important to monitor the long term effects of the evacuation in the future. PMID- 26561046 TI - Time-of-Flight Magnetic Resonance Angiography With Sparse Undersampling and Iterative Reconstruction: Comparison With Conventional Parallel Imaging for Accelerated Imaging. AB - OBJECTIVES: The aim of this study was to evaluate the clinical feasibility of accelerated time-of-flight (TOF) magnetic resonance angiography with sparse undersampling and iterative reconstruction (sparse TOF). MATERIALS AND METHODS: The local institutional review board approved the study protocols. Twenty healthy volunteers were recruited (mean age, 31.2 years; age range, 22-52 years; 14 men, 6 women). Both sparse TOF and parallel imaging (PI) TOF were obtained on a 3 T scanner. Acceleration factors were 3, 4, 5, 6, and 8 for sparse TOF (Sp 3*, Sp 4*, Sp 5*, Sp 6*, and Sp 8*, respectively) and 2, 3, 4, and 6 for PI TOF (PI 2*, PI 3*, PI 4*, and PI 6*, respectively). Images were reconstructed on the scanner, and maximum intensity projection images were subjected to visual evaluation, wherein each segment of the major brain arteries was independently evaluated by 2 radiologists on a 4-point scale (1, poor; 2, limited; 3, moderate/good quality for diagnosis; and 4, excellent). As a quantitative evaluation, the apparent contrast-to-background deviation (apparent CBD) was calculated at the level of the basilar artery and the pons. RESULTS: A total number of 1800 segments were subjectively evaluated. There was substantial agreement regarding vessel visualization (kappa = 0.759). Sparse TOF received scores above 3 (good for diagnosis) at any acceleration factor up to the third segments of major arteries. The middle and distal segments of PI 4* and PI 6* were graded below 3 (limited or poor diagnostic value). Sp 3*, 4*, 5*, and 6* retained diagnostic information (graded above 3), even at distal segments. The apparent CBD of sparse TOF at any acceleration factor was equivalent to that of PI 2*, whereas the apparent CBD of PI 3*, PI 4*, and PI 6* attenuated with the acceleration factor. CONCLUSIONS: Sparse TOF can achieve better image quality relative to PI TOF at higher acceleration factors. The diagnostic quality of distal branches (A2/3, M4, P4) was maintained with Sp 6*, which achieved a shorter acquisition time less than half of PI 2*. PMID- 26561047 TI - Longitudinal Assessment of Renal Perfusion and Oxygenation in Transplant Donor Recipient Pairs Using Arterial Spin Labeling and Blood Oxygen Level-Dependent Magnetic Resonance Imaging. AB - OBJECTIVES: The aims of this study were to assess renal function in kidney transplant recipients and their respective donors over 2 years using arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and to prospectively evaluate the effect of losartan on functional MRI measures in recipients. MATERIALS AND METHODS: The study included 15 matched pairs of renal transplant donors and recipients. Arterial spin labeling and BOLD MRI of the kidneys were performed on donors before transplant surgery (baseline) and on both donors and recipients at 3 months, 1 year, and 2 years after transplant. After 3 months, 7 of the 15 recipients were prescribed 25 to 50 mg/d losartan for the remainder of the study. A linear mixed-effects model was used to evaluate perfusion, R2*, estimated glomerular filtration rate, and fractional excretion of sodium for changes across time or associated with losartan treatment. RESULTS: In donors, cortical perfusion in the remaining kidney decreased by 50 +/- 19 mL/min per 100 g (11.8%) between baseline and 2 years (P < 0.05), while cortical R2* declined modestly by 0.7 +/- 0.3 s-1 (5.6%; P < 0.05). In transplanted kidneys, cortical perfusion decreased markedly by 141 +/- 21 mL/min per 100 g (34.2%) between baseline and 2 years (P < 0.001), while medullary R2* declined by 1.5 +/- 0.8 s-1 (8.3%; P = 0.06). Single-kidney estimated glomerular filtration rate increased between baseline and 2 years by 17.7 +/- 2.7 mL/min per 1.73 m (40.3%; P < 0.0001) in donors and to 14.6 +/- 4.3 mL/min per 1.73 m (33.3%; P < 0.01) in recipients. Cortical perfusion at 1 and 2 years in recipients receiving 25 to 50 mg/d losartan was 62 +/- 24 mL/min per 100 g higher than recipients not receiving the drug (P < 0.05). No significant effects of losartan were observed for any other markers of renal function. CONCLUSIONS: The results suggest an important role for noninvasive functional monitoring with ASL and BOLD MRI in kidney transplant recipients and donors, and they indicate a potentially beneficial effect of losartan in recipients. PMID- 26561048 TI - Dual-Energy Computed Tomography Angiography of the Lower Extremity Runoff: Impact of Noise-Optimized Virtual Monochromatic Imaging on Image Quality and Diagnostic Accuracy. AB - OBJECTIVE: The aim of this study was to evaluate the impact of a noise-optimized virtual monochromatic imaging algorithm (VMI+) on image quality and diagnostic accuracy at dual-energy computed tomography angiography (CTA) of the lower extremity runoff. MATERIALS AND METHODS: This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by the local institutional review board. We evaluated dual-energy CTA studies of the lower extremity runoff in 48 patients (16 women; mean age, 63.3 +/- 13.8 years) performed on a third-generation dual-source CT system. Images were reconstructed with standard linear blending (F_0.5), VMI+, and traditional monochromatic (VMI) algorithms at 40 to 120 keV in 10-keV intervals. Vascular attenuation and image noise in 18 artery segments were measured; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Five-point scales were used to subjectively evaluate vascular attenuation and image noise. In a subgroup of 21 patients who underwent additional invasive catheter angiography, diagnostic accuracy for the detection of significant stenosis (>=50% lumen restriction) of F_0.5, 50-keV VMI+, and 60-keV VMI data sets were assessed. RESULTS: Objective image quality metrics were highest in the 40- and 50-keV VMI+ series (SNR: 20.2 +/- 10.7 and 19.0 +/- 9.5, respectively; CNR: 18.5 +/- 10.3 and 16.8 +/- 9.1, respectively) and were significantly (all P < 0.001) higher than in the corresponding VMI data sets (SNR: 8.7 +/- 4.1 and 10.8 +/- 5.0; CNR: 8.0 +/- 4.0 and 9.6 +/- 4.9) and F_0.5 series (SNR: 10.7 +/- 4.4; CNR: 8.3 +/- 4.1). Subjective assessment of attenuation was highest in the 40- and 50-keV VMI and VMI+ image series (range, 4.84-4.91), superior to F_0.5 (4.07; P < 0.001). Corresponding subjective noise assessment was superior for 50-keV VMI+ (4.71; all P < 0.001) compared with VMI (2.60) and F_0.5 (4.11). Sensitivity and specificity for detection of 50% or greater stenoses were highest in VMI+ reconstructions (92% and 95%, respectively), significantly higher compared with standard F_0.5 (87% and 90%; both P <= 0.02). CONCLUSIONS: Image reconstruction using low kiloelectron volt VMI+ improves image quality and diagnostic accuracy compared with traditional VMI technique and standard linear blending for evaluation of the lower extremity runoff using dual-energy CTA. PMID- 26561049 TI - Pretreatment Prognostic Value of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Vascular, Texture, Shape, and Size Parameters Compared With Traditional Survival Indicators Obtained From Locally Advanced Breast Cancer Patients. AB - OBJECTIVES: The aim of this study was to determine if associations exist between pretreatment dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) based metrics (vascular kinetics, texture, shape, size) and survival intervals. Furthermore, the aim of this study was to compare the prognostic value of DCE-MRI parameters against traditional pretreatment survival indicators. MATERIALS AND METHODS: A retrospective study was undertaken. Approval had previously been granted for the retrospective use of such data, and the need for informed consent was waived. Prognostic value of pretreatment DCE-MRI parameters and clinical data was assessed via Cox proportional hazards models. The variables retained by the final overall survival Cox proportional hazards model were utilized to stratify risk of death within 5 years. RESULTS: One hundred twelve subjects were entered into the analysis. Regarding disease-free survival-negative estrogen receptor status, T3 or higher clinical tumor stage, large (>9.8 cm) MR tumor volume, higher 95th percentile (>79%) percentage enhancement, and reduced (>0.22) circularity represented the retained model variables. Similar results were noted for the overall survival with negative estrogen receptor status, T3 or higher clinical tumor stage, and large (>9.8 cm) MR tumor volume, again all been retained by the model in addition to higher (>0.71) 25th percentile area under the enhancement curve.Accuracy of risk stratification based on either traditional (59%) or DCE-MRI (65%) survival indicators performed to a similar level. However, combined traditional and MR risk stratification resulted in the highest accuracy (86%). CONCLUSIONS: Multivariate survival analysis has revealed that model retained DCE-MRI variables provide independent prognostic information complementing traditional survival indicators and as such could help to appropriately stratify treatment. PMID- 26561050 TI - A Standardized Parameter-Free Algorithm for Combined Intravoxel Incoherent Motion and Diffusion Kurtosis Analysis of Diffusion Imaging Data. AB - OBJECTIVES: The aims of this study were to implement and systematically evaluate the performance of a new parameter-free segmented algorithm for analysis of diffusion imaging data using a combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) model of spin diffusion in comparison with the simpler intravoxel incoherent motion (IVIM) model. MATERIALS AND METHODS: A multistep algorithm was implemented intended to separate diffusion kurtosis from IVIM effects in multi-b-value diffusion measurements using an adaptive b-value threshold technique. For each possible b-value threshold (separating diffusion and perfusion effects), diffusion kurtosis analysis of high b-values is followed by IVIM analysis keeping kurtosis parameters fixed. The b-value threshold with smallest Akaike information criterion is chosen as best model solution. The algorithm was tested in diffusion data sets of the upper abdomen from 8 healthy volunteers with 16 different b-values and compared with a standard multistep IVIM analysis. RESULTS: The proposed algorithm could successfully be applied to all data sets and provided a significantly better fit of the observed signal decay in all assessed organs (all P < 0.03). Using the proposed IVIM-DKI model of diffusion instead of an IVIM model had a systematic impact on the resulting IVIM parameters: The pure diffusion coefficient and the pseudodiffusion coefficient were significantly increased (P < 0.03 in all assessed organs), accompanied by a decrease in the perfusion fraction in liver, pancreas, renal cortex, and skeletal muscle (all P < 0.02). Optimal b-value thresholds separating diffusion from perfusion effects had a tendency to lower values when the IVIM-DKI model was used. CONCLUSIONS: The proposed algorithm provides a new approach for separation of IVIM and kurtosis effects of diffusion data without organ-specific adaptation. PMID- 26561053 TI - Interleukin 17-A inhibition in the treatment of psoriasis. AB - Interleukin (IL) 17-A appears to be integral to the pathogenesis of chronic plaque psoriasis. Recent clinical trials have shown that blockade of this cytokine with the biologic therapies--secukinumab, ixekizumab and brodalumab- have led to unprecedented treatment efficacy for psoriasis. In addition, their dual efficacy towards psoriatic arthritis increases their potential clinical utility and they promise to be an important treatment option for patients who have tumour necrosis factor inhibitor resistant disease. Here, we present the evidence for the high treatment efficacy of the IL-17A inhibitors but also discuss some potential questions and areas of research needed, including the lack of evidence behind the drug survival, immunogenicity and safety profile. PMID- 26561051 TI - Pharmacological Preventions of Brain Injury Following Experimental Germinal Matrix Hemorrhage: an Up-to-Date Review. AB - Germinal matrix hemorrhage (GMH) is defined as the rupture of immature blood vessels in the subependymal zone of premature infants with significant mortality and morbidity. Considering the notable social and ecological stress brought by GMH-induced brain injury and sequelae, safe and efficient pharmacological preventions are badly needed. Currently, several appropriate animal models are available to mimic the clinical outcomes of GMH in human patients. In the long run, hemorrhagic strokes are the research target. Previously, we found that minocycline was efficient to alleviate GMH-induced brain edema and posthemorrhagic hydrocephalus (PHH) in rats, which may be closely related to the activation of cannabinoid receptor 2 (CB2R). However, how the two molecules correlate and the underlined molecular pathway remain unknown. To extensively understand current experimental GMH treatment, this literature review critically evaluates existing therapeutic strategies, potential treatments, and potentially involved molecular mechanisms. Each strategy has its own advantages and disadvantages. Some of the mechanisms are still controversial, requiring an increasing number of animal experiments before the therapeutic strategy would be widely accepted. PMID- 26561054 TI - Dendritic Cells in Esophageal Adenocarcinoma: The Currently Available Information and Possibilities to use Dendritic Cells for Immunotherapeutic Approaches. AB - Esophageal adenocarcinoma (EAC) is the second frequent cancer of the esophagus. Barrett's esophagus (BE) takes precedence over EAC. BE is a metaplastic change of the stratified squamous epithelium to the intestinal columnar epithelium due to the acidic gastrointestinal reflux. Further, the disease takes the hyperplastic stage followed by EAC. An initial immune response is an essential reaction of a body to an occurrence of alien/modified cells to be removed. It has been appreciated that an inflammatory reaction occurs in the early stages of EAC or even in BE. Dendritic cells (DCs) play a key role in a frontier of an immune response due to their advanced ability to recognize foreign antigens and mobilize naive T cells to effectors. However, in a cancer condition, tumor-delivered immunosuppression occurs in a variety of mechanisms that alter/switch the functionality of DCs from immune activating to immune suppressive cells. In this brief review, we consider tumor-induced paths of a capacity of tumor cells to down-regulate DCs, with a focus on EAC, and also discuss a possibility to use DCs for immunotherapeutic approaches. Indeed, DCs represent a promising tool for developing new immunotherapeutic approaches for cancer treatment including EAC. It has been reported to achieve effective DC-mediated immune responses by raising anti-tumor cytotoxic T cell responses against multiple cancer antigens through loading DCs with total tumor RNA. However, more studies should be performed in order to understand a precise role in tumor-induced mechanisms of DC suppression in BE/EAC. Likely, these mechanisms should involve general carcinogenic and EAC specific pathways. PMID- 26561052 TI - Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection. AB - INTRODUCTION: Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection. PATIENTS AND METHODS: Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped. RESULTS: The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT homozygotes) had higher maximum level of serum creatinine than the carriers of G allele (GT-heterozygotes and GG-homozygotes; median 326, range 102-1041 vs. median 175, range 51-1499 MUmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3-14 vs. median 6, range 2-15 days; p = 0.032). The rare A-allele carriers (i.e. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74-170 vs.116, range 86-162 mmHg, p = 0.019, and median 68, range 40-90 vs. 72, range 48-100 mmHg; p = 0.003, respectively). CONCLUSIONS: Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection. PMID- 26561055 TI - Antiatherosclerotic and Cardioprotective Effects of Time-Released Garlic Powder Pills. AB - Garlic is believed to produce beneficial changes in different cardiovascular risk factors, thus possessing antiatherosclerotic properties. The hypotensive and cholesterol-lowering effects were investigated in two studies in men with mild arterial hypertension and in men with mild hypercholesterolemia. Eight-week treatment resulted in the reduction of both systolic and diastolic blood pressure by 5.2% (P=0.008) and 4.0% (P=0.014), respectively. In hypolipidemic study, the 12-week treatment resulted in a decrease in LDL cholesterol by 11.8% (P=0.002), while HDL cholesterol increased by 11.5% (P=0.013). In men with cerebral atherosclerosis it has been demonstrated that 14-days treatment inhibited ADP induced platelet aggregation by 25.4% (P<0.05) and increased plasma fibrinolytic activity by 22.4% (P<0.05). One more study was performed in high-risk patients to evaluate the changes of prognostic cardiovascular risk that was calculated using algorithms derived from Framingham and Muenster Studies. Twelve-months treatment lowered 10-years prognostic risk of CHD by 13.2% in men (P=0.005), and by 7.1% in women (P=0.040). Ten-year prognostic risk of acute myocardial infarction and sudden coronary death was lowered by 26.1% in men (P=0.025). The Atherosclerosis Monitoring and Atherogenicity Reduction Study (AMAR) was designed to estimate the effect of two-year treatment with garlic powder pills on the progression of carotid atherosclerosis in asymptomatic men. A significant correlation has been revealed between the changes in blood serum atherogenicity and the changes in carotid intima-media thickness (r=0.144, P=0.045). Evidence obtained from these studies as well as series of double-blinded placebo-controlled clinical trials indicates that garlic powder pills are effective for prevention of cardiovascular disorders. PMID- 26561056 TI - Guggulsterone for Chemoprevention of Cancer. AB - Guggulsterone [4, 17(20)-pregnadiene-3, 16-dione] is a plant sterol derived from the gum resin of the tree Commiphora wightii. The gum resin of the guggul tree has been used in traditional medicine for centuries to treat obesity, liver disorders, internal tumors, malignant sores, ulcers, urinary complaints, intestinal worms, leucoderma, sinus, edema and sudden paralytic seizures. Guggulsterone has been shown to modulate the nuclear receptors, farnesoid X receptor, pregnane X receptor, CYP 2b10 gene expression, and the bile salt export pump for cholesterol elimination. Recent research indicates that the active components of gum guggul, E- and Zguggulsterone have the potential to both prevent and treat cancers. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases, inhibition of Akt, and activation of JNK. Guggulsterone modulates the expression of gene products involved in metastasis (MMP-9, COX-2, and VEGF) of tumor cells. Guggulsterone mediates gene expression through the modulation of several transcription factors, including NF-kappaB, STAT3, C/EBPalpha, androgen receptor, and glucocorticoid receptors. This review describes the anti-cancer properties, molecular targets, and the apoptotic effects of guggulsterone. PMID- 26561057 TI - Antiviral Natural Products Against Chronic Hepatitis B: Recent Developments. AB - Hepatitis B virus (HBV) is inherently a hepatotropic virus that causes acute and chronic hepatitis in about one-third of world population. Of the estimated 360 million chronically infected individuals, more than one million die of liver cirrhosis, fulminant liver failure or hepatocellular carcinoma (HCC) every year. Though there is an effective vaccine available, failure to protection because of vaccine-escape viral mutants in some population is also reported. Moreover, all the currently approved antiviral drugs have their limitations, too. Interferon (IFN-alpha) has limited efficacy and a high incidence of adverse side-effects in a proportion of chronic patients. Nucleos(t)ide analogs like, lamivudine, adefovir, tenofovir and entecavir are very effective in treating chronic hepatitis B (CHB), but long-term therapy eventually leads to drug-resistance. As an alternative approach, natural or plant products have provided promising therapeutics in modern pharma industry. Owing to their characteristics of high chemical diversity and biochemical specificity, natural products offer great promises as potentially effective antiviral drugs. A broad spectrum of phytochemicals including flavonoids (e.g., Vogonin), terpenes (e.g., Artemisinin), alkaloids (e.g., Oxymatrine), polyphenolics (e.g., geraniin), saponins (e.g., Astragaloside IV) and lignans (e.g., Helioxanthin) has been isolated and investigated for anti-HBV activities in vitro as well as in vivo. Nevertheless, these promising compounds have different and overlapping mechanisms of action by either inhibiting viral antigens secretion or suppression of DNA replication. The present article reviews the recent developments in anti-HBV natural products. PMID- 26561058 TI - Visit-to-visit blood pressure variability and classes of antihypertensive agents; associations with artery remodeling and the risk of stroke. AB - Recent studies have shown that visit-to-visit blood pressure (BP) variability was emerging as an independent risk factor for stroke. Although the mechanism is not fully understood, artery remodeling would be closely associated with the relationship between visit-to-visit BP variability and stroke. In addition, the class of antihypertensive agents is suggested to be an important determinant of visit-to-visit BP variability. This review article summarizes the recent literature on these topics. In the elderly hypertensives, strict BP control using calcium channel blockade would play a crucial role to prevent stroke via reducing the visit-to-visit BP variability. PMID- 26561059 TI - Mitochondrial genome sequencing in atherosclerosis: what's next? AB - Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease. PMID- 26561060 TI - Cardioprotective effects of Aronia melanocarpa anthocynanins. From laboratory experiments to clinical practice. AB - The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeberry) are known to be a reach source of these polyphenols. Moreover, its extracts were shown to express strong antioxidant, antiinflammatory, vasorelaxant and antithrombotic properties. The aim of the review is to summarize the results of the hitherto research regarding the biological effects at the molecular and clinical level. PMID- 26561061 TI - The potential for circulating microRNAs in the diagnosis of myocardial infarction: a novel approach to disease diagnosis and treatment. AB - MicroRNAs (miRNAs) are a class of small regulatory RNAs that control several cellular processes that may contribute to development of cardiovascular disease (CVD) and the pathophysiological consequences of myocardial infarction (MI). Only a very small-numbers of biomarkers in MI (e.g., Troponin) have been identified, which are sufficiently sensitive, specific and robust. There is growing evidence of an association between specific miRNAs in the pathogenesis of MI. miRNAs are transported within the systemic circulation via exosomes and microparticles, and are therefore detectable in blood, urine, saliva, and other fluid compartments. Dysregulation of myocardial-derived miRNAs, such as miR-1, miR-133, miR-499, and miR-208, have been identified as potential biomarkers in MI. Furthermore, alteration of the levels of some miRNAs during stress-induced apoptosis is reported as a novel therapeutic strategy for cardiac disease. Modulation of mir 24 appears to inhibit cardiomyocyte apoptosis, attenuate infarct size, and reduce cardiac dysfunction. A greater knowledge on the molecular mechanism underlying the functional role of emerging miRNAs, could provide novel insights into identifying of new biomarkers. This review highlights several recent preclinical and clinical studies on the role of miRNAs in myocardial infarction; novel miRNA based therapeutic approaches for therapeutic intervention, and potential circulating miRNA to be served as biomarkers in patients with suspected MI. PMID- 26561062 TI - Oxidative stress and Parkinson's disease: New hopes in treatment with herbal antioxidants. AB - Parkinson's disease (PD) is a neurodegenerative disorder due to dopamine deficit in substatia nigra. PD is mainly a sporadic disease with unestablished etiology. However, exposure to environmental toxins, head trauma, inflammation, and free radicals are potential reasons. Recently, the role of oxidative stress in neurological abnormalities, including PD, has been particularly addressed. Antioxidant remedies, particularly herbal antioxidants, have revealed new perspectives of research and therapy as possible preventive and therapeutic approaches for PD. In this paper, we reviewed the recently published papers on the effects of herbal medicines on PD alongside the pathogenesis of PD with regard to oxidative stress. PMID- 26561063 TI - Autism: Pathophysiology and Promising Herbal Remedies. AB - Autism is a comprehensive growth abnormality in which social skills, language, communication, and behavioral skills are developed with delay and as diversionary. The reasons for autism are unclear, but various theories of genetics, immunity, biological, and psychosocial factors have been proffered. In fact, autism is a complex disorder with distinct causes that usually co-occur. Although no medicine has been recognized to treat this disorder, pharmacological treatments can be effective in reducing its signs, such as self-mutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleeping disorders. Recently, complementary and alternative approaches have been considered to treat autism. Ginkgo biloba is one of the most effective plants with an old history of applications in neuropsychological disorders which recently is used for autism. The present review discusses the recent findings, pathophysiology, and etiology of autism and thereafter addresses the promising results of herbal remedies. PMID- 26561064 TI - Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine. AB - Diseases associated with chronic inflammatory pathology claim a major share of worldwide deaths each year. A principal reason behind the huge number of casualties is associated with mild or unnoticed symptoms for long period of time since the outset, and that specific treatment options for these diseases have not yet emerged. Current anti-inflammatory drugs essentially have become ineffective for long term protection from these diseases as they also interfere with essential cellular pathways and associated toxicities. Notably, recent studies with a number of phytochemicals have shown promising results. These compounds isolated from various medicinal plants express their anti-inflammatory activities by down regulating expression of several crucial pro-inflammatory mediators. These are mostly antioxidants; inhibit induction of key transcription factors like nuclear factor kappa B (NF-kappaB) that are responsible for expression of proinflammatory mediators, and other growth regulators. Definitely, some of these compounds have the potential to be developed into new therapeutic agents to better control inflammation associated diseases in near future. This review summarizes recent findings on the molecular mechanisms through which various inflammatory activities are linked to disease progression and a group of natural products that have shown promise in controlling these processes. PMID- 26561065 TI - Flaxseed and Diabetes. AB - Flaxseed contains 32% to 45% of its mass as oil of which 51% to 55% is alpha linolenic acid. Flax lignan complex and secoisolariciresinol diglucoside (SDG) have been isolated from flaxseed. Flaxseed and its components have antioxidant, hypolipidemic and hypoglycemic effects. These are mostly due to the SDG content. Oxidative stress has been implicated in both type 1 and type 2 diabetes. Flaxseed, flaxseed oil and flax lignan complex have not been investigated as to whether they reduce the incidence of diabetes and/or delay the development of diabetes. However, their effects on serum glucose have been studied. Flaxseed and flax lignan complex improve glycemic control. Animal models of type I diabetes involving streptozotocin administration or utilizing Bio-Breed diabetic (BBdp) prone rats are associated with oxidative stress. SDG treatment reduced the incidence of diabetes using serum glucose levels by 75% in the streptozotocin model of diabetes and by 72% in the BBdp rat model of diabetes. These reductions in development of diabetes were associated with decreases in oxidative stress measured by serum and pancreatic malondialdehyde (MDA). SDG delays the development of diabetes in Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and this effect was associated with a reduction in serum MDA and glycated haemoglobin A1C. The data suggest that SDG may have a great potential for reducing the incidence of type 1 diabetes and delaying the development of type 2 diabetes in humans. PMID- 26561066 TI - Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside. AB - Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease, stroke and peripheral arterial vascular diseases. PMID- 26561067 TI - Biomarkers of Subclinical Atherosclerosis and Natural Products as Complementary Alternative Medicine. AB - Cardiovascular diseases (CVD) are considered the leading cause of morbidity and mortality from chronic diseases in the world. In addition, about 20% of first and recurrent acute myocardial infarctions (MI) are silent. In this context, subclinical atherosclerosis culminates in evident CVD, through the evolution of early risk factors such as hypercholesterolemia, hypertriglyceridemia and others. The main problem in CVD is related to the long-time between the start of the subclinical atherosclerosis and the manifestation of the disease. The identification of subjects at risk of such events is obviously substantial, since identification leads to implementation and compliance with effective preventive measures that reduce such risk. In this sense, this review demonstrates biomarkers as an alternative to early detection of subclinical atherosclerosis. One of the proposed biomarkers is the Ischemia-modified albumin (IMA), being considered a promising biochemical biomarker for atherosclerotic conditions. Another marker that is gaining strength and is associated with the IMA are the advanced oxidation protein products (AOPP), its measurement provides information on the level of exposure to potentially harmful changes to proteins and metabolic control. And last but not least we have nitric oxide as an early marker mainly related to endothelial dysfunction. In this review also is evidenced the use of the Campomanesia xanthocarpa, a plant native to southern region from Brazil extensively used as complementary and alternative medicine, and natural products to reduce protein oxidation and improve the availability of nitric oxide and consequently vascular function, reducing the risk for development of CVD. PMID- 26561069 TI - Potential of Natural Products of Herbal Origin as Monoamine Oxidase Inhibitors. AB - Monoamine oxidase (MAO, E.C. 1.4.3.4) is a flavin-adenine type of enzyme with two isoforms referred to MAO-A and MAO-B that function for oxidation of monoamines. While MAO-A inhibitors are effective as antidepressant and anxiolytic drugs (e.g. chlorgyline, moclobemide, and lazabemide), inhibitors of MAO-B (e.g. Ldeprenyl, pargyline, and rasagiline) are used against neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Considering the need for novel MAO inhibitors due to side effects of the current ones, natural products have become attractive targets for researchers. Up till now, many studies revealed strong MAO inhibitory activity of flavonoid, xanthone, alkaloid, and coumarin derivatives from herbal sources, which also become good models for the synthetic MAO inhibitors. For this purpose, the present review focuses on examples of in vitro and in vivo MAO-inhibiting natural compounds of plant origin from a wide variety of chemical classes isolated mainly between 2000 - 2015. PMID- 26561068 TI - Cardiometabolic Risk Related to the Association of hypertriglyceridemia-Low HDLc. AB - AIMS: High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases often associated with anomalies in other lipids or lipoproteins. However, results from randomized trials, suggesting that low high density lipoprotein cholesterol (HDLc) might not cause cardiovascular disease, as originally thought, have generated renewed interest in increased concentrations of TG. The objective has been to determine the prevalence and factors associated with hypertrigliceridemia (HTG) and with low HDLc. METHODS: Patients, included in the HTG Registry of the Spanish Association of Atherosclerosis, have been analyzed and anthropometric as well as metabolic data have been collected from them. RESULTS: 1349 patients have been evaluated. Low HDLc has been found in 60.86% (821). Factors significantly associated with low HDLc and HTG were the female sex, being overweight with an increase in the body mass index, using tobacco, diabetes mellitus, low-alcohol consumption and a low exercise rate. Among them, two types of association may be identified with anthropometric variables (especially in men) and metabolic variables (diabetes mellitus and metabolic syndrome). No significant differences have been found insofar as the prevalence of cardiovascular illness between both groups. CONCLUSIONS: HTG - low HDLc association is very frequent and it is related to overweight-obesity and other metabolic disorders such as diabetes mellitus with or without metabolic syndrome. In addition, these findings underscore the intricate relationship between HDLc, TG, and glucose metabolism that need to be studied simultaneously. In this context, TG lowering treatment is suggested to be more strongly recommended to address the residual risk of atherosclerotic cardiovascular disease. PMID- 26561070 TI - Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women. AB - Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement therapy prevents the development of atherosclerosis in menopausal women. However, the results of the largest international trials involving thousands of women have completely destroyed this hope. The modern perspective for the development of effective and safe drugs to enhance the quality of life and to prevent atherosclerosis progression in postmenopausal women may be the use of phytoestrogens, the substances of plant origin possessing estrogen- like effects, and possibly providing anti-atherosclerotic and anti-climacteric action. Phytoestrogens are often considered as a possible alternative to hormone replacement therapy, since they are believed to alleviate some symptoms of menopause. However, until now there is no exact evidence to consider phytoestrogens as the substances that protect women from atherosclerosis. It should be noted that the data from clinical studies with inconsistent results are mainly inconsistent per se, as most of the studies have serious limitations due to the study design and the participants' compliance. Nevertheless, there is a substantial evidence that phytoestrogens have the potential to address several conditions and diseases associated with the menopausal transition. Phytoestrogens, at least, can potentially reduce atherosclerosis and atherosclerosis-related diseases through multiple mechanisms, by regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system. However, a skepticism exists concerning the true potential of phytoestrogens to beneficially modify these processes. An analysis of findings from supplementing the diet with phytoestrogens has failed, in general, to confirm them as the agents responsible for beneficial cardiovascular effects. Fortunalely, now there is a growing interest to the use of phytoestrogens for primary prevention of cardiovascular disease in postmenopausal women. Clinical and epidemiologic data indicate that phytoestrogens possess anti-atherosclerotic effects and may be used to prevent and treat cardiovascular diseases, and that adding phytoestrogens to the diet can contribute to the health of postmenopausal women. This review discusses the effects of phytoestrogens possibly beneficial for cardiovascular health, and how these effects could retard the progression of atherosclerosis, as well as the areas that need further investigation. PMID- 26561071 TI - Mechanism of Treatment of Kidney Deficiency and Osteoporosis is Similar by Traditional Chinese Medicine. AB - Traditional Chinese medicine (TCM) is a theoretical based system and is completely different from western medicine and states that numerous diseases, especially chronic diseases, are cured or relieved. "Zheng" (syndrome) is a summarization of the pathological changes which take place during the different stages of the development of a disease, including its location, cause and nature as well as the state of both Xie-qi (pathogenic factors) and Zheng-qi (healthy energy). Compared to a single symptom, syndrome can demonstrate the nature of a disease more extensively, completely and correctly. However, it is difficult to compare "Zheng" to the western medicine theory, which is based on scientific evidence for the diagnosis and treatment of a specific disease. Estrogen deficiency is a major pathogenetic factor in bone loss after menopause and oophorectomy with the subsequent risk of developing osteoporosis. According to TCM theory, the kidney stores essence and this can transform into bone marrow to nourish the bones, strenghthen the skeleton by promoting growth and repair. The kidney deficiency can decrease the estrogen level adjusted by the gonadal axis, causing osteoporosis. Traditional Chinese medicines tonifying the kidney can significantly enhance the level of estrogen to alleviate osteoporosis. In combination with other evidence, we further deduce that the syndrome as defined within TCM has a similar pathological mechanism to that defined by western medicine. If TCM theory is to be understood and accepted, and further fused with the western medicine theory, the micro pathological basis of TCM syndrome must be investigated extensively, which will lead to bridging the two theories together. The fusion of TCM with western medicine will pay more attention to analyzing the common nature and difference of disease and syndrome. This paper reviews the way forward for new translational advances. PMID- 26561072 TI - Environmental Toxicant Exposure and Cancer: The Role of Epigenetic Changes and Protection by Phytochemicals. AB - Exposure to environmental toxicants is a well-documented predisposing factor for cancer. Although genetic alterations have long been known to occur through exposure to some environmental carcinogens, there is another layer of genome regulatory system named epigenetic system. Epigenetics is defined as any reversible and heritable change in cellular patterns of gene expression that does not alter DNA sequence. This layer of gene control plays a key role in early stages of carcinogenesis by reprogramming cells to what is known as cancer stem cells, a process with great similarities to somatic cell reprogramming into "induced pluripotent stem cell". Environmental toxicants could directly promote carcinogenesis through disturbing promoter CpG island hypermethylation, and silencing of tumor suppressor genes, hypomethylation of transposable elements and genomic instability induced by environmental toxicants. Environmental toxicants could also indirectly affect epigenetic programming of nucleus through inducing inflammatory signaling pathways that converge on NF-kappaB or STAT3 activation. Considering the reversibility of epigenetic alterations and their pivotal role in early carcinogenesis, reversion of these alterations could be a promising approach for chemoprevention. Selected phytochemicals have shown desirable effects through regulation of the most important epigenetic mechanisms including DNA methylation, histone modifications and microRNA expression, as well as modulation of SIRT-1 and STAT-3 signaling pathways. The present review aims to outline the epigenetic mechanisms underlying carcinogenic effects of environmental toxicants, and the protective effects of phytochemicals in reversing epigenetic aberrations in the regulatory pathways steering normal cell homeostasis. PMID- 26561073 TI - Role of Micronutrients on Subclinical Atherosclerosis Micronutrients in Subclinical Atherosclerosis. AB - Atherosclerotic cardiovascular disease (CVD) leading to coronary heart disease is the leading cause of morbidity and mortality in the world. Nutrition is one of the key factors in the etiology of atherosclerosis. Micronutrient supplements are widely used to prevent many chronic diseases including atherosclerosis. However, scientific evidence regarding this issue is still insufficient and current data on the association of dietary micronutrients and CVD risk is contradictory. Most of the randomized studies have failed to demonstrate beneficial effects of micronutrient supplementation on markers of subclinical atherosclerosis. In this review, role of each micronutrient on subclinical atherosclerosis will be evaluated thoroughly. PMID- 26561074 TI - Herba Epimedii: An Ancient Chinese Herbal Medicine in the Prevention and Treatment of Osteoporosis. AB - Herba Epimedii (HEP) known as YinYangHuo in Chinese is the dried leaf of the Epimediium, and has been historically used in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). Here, we review the historical TCM interpretation of the action of HEP, its use in clinical trials, its main phytochemical constituents and its pharmacological findings. 85 clinical trials were identified which used HEP in TCM prescriptions with other herbs to treat primary and secondary osteoporosis from 2005 to now. More than 60 individual compounds were isolated and characterized from HEP and studied in various animal and cell models. HEP and its constituents exhibited a variety of anti-resorptive and bone formation-stimulating effects, which target different pathways in the bone remodeling cycle. These compounds may provide new perspectives in alternative treatment regimes and reveal novel chemical scaffolds for the development of anti-osteoporotic drugs. These approaches are also useful for guiding our research to employ an integrative therapeutic approach to treat complex diseases such as osteoporosis diseases which could be superior to the conventional single target - single drug approach. PMID- 26561075 TI - Brain Protection and Cognitive Function: Cocoa Flavonoids as Nutraceuticals. AB - Cognitive decline and dementia are major public health social problems, suggesting the specific need to provide research into risk factors for cognitive decline as priority topic. Increasing evidence supports the hypothesis that oxidative stress and neuroinflammation might play a crucial role in the pathophysiology of cognitive decline. Further, cognitive dysfunction and dementia in Alzheimer's disease as well as in vascular dementia seem to be also the consequence of cerebral blood flow decrease and deregulation, also suggesting a putative pathophysiological convergence of mechanisms between atherosclerosis and Alzheimer's disease. In keeping with this, a growing interest has been addressed to flavonoids as potential nutraceuticals with neuroprotective effects. Of interest, cocoa beans have been described as a fundamental source of anti-oxidant flavonoids with the flavan-3-ols and their derivatives being present in high concentrations. Therefore, recent studies specifically focused on the favorable effects of flavonoid-rich cocoa and chocolate on cerebrovascular risk factors and cognitive function. Aim of this review is to summarize new findings concerning the cocoa effects on cognitive function, particularly focusing on some putative mechanisms of vascular and antioxidant action involved in preventing dementia. PMID- 26561076 TI - Periodontitis and Periodontal Disease - Innovative Strategies for Reversing the Chronic Infectious and Inflammatory Condition by Natural Products. AB - Oral microbiota of the mouth is the most diverse microbial community in the human body and plays a decisive role in the emergence and evolution of gingival pathology, contributing as well to the host general health condition, based on complex interactions established between the microbial community members and the host. A specific shift in the quantity and diversity of the microbial community developed on dental and mucosal surfaces, could lead to the occurrence of chronic inflammation mediated by the overproduction of pro-inflammatory cytokines. The mechanical treatment and current medication efficiency for the periodontal disease is limited in time due to the rapid plaque forming. Also, the antimicrobial treatment is limited by the sessile growth of the microorganisms, resulting in a poor biofilm penetration by biocides or antibiotics. In line with that, the attention of the scientific community shifted to ethnopharmacology as a complementary, or alternative therapeutic option for fighting infections with resistant bacteria. The vegetal and bee products are an important source of bioactive compounds, acting as harmless antimicrobials and periodontal inflammation suppressors. Vegetable bioproducts have been proven to exhibit multiple antipathogenic effects, such as microbicidal activity, virulence attenuation, and synergistic effects between the components found in the complex vegetal matrixes, or with conventional biocides, as well as immunomodulatory effects. The purpose of this review is to highlight the importance of vegetable products as a possible complementary treatment for periodontitis and their potential for the development of innovative therapeutic strategies. PMID- 26561077 TI - Paresthesia: A Review of Its Definition, Etiology and Treatments in View of the Traditional Medicine. AB - OBJECTIVE: To search major Islamic Traditional Medicine (ITM) textbooks for definition, etiology and medicinal plants used to manage 'khadar' or 'paresthesia', a common sensory symptom of multiple sclerosis (MS) and peripheral neuropathies. In addition, the conformity of the efficacy of ITM-suggested plants with the findings from modern pharmacological research on MS will be discussed. METHODS: Data on the medicinal plants used to treat 'khadar' were obtained from major ITM texts. A detailed search in PubMed, ScienceDirect, Scopus and Google Scholar databases was performed to confirm the effects of ITM-mentioned medicinal plants on MS in view of identified pharmacological actions. RESULTS: Moringa oleifera Lam., Aloe vera (L.) Burm.f., Euphorbia species, Citrullus colocynthis (L.) Schrad., and Costus speciosus (Koen ex. Retz) Sm. are among the most effective ITM plants for the management of 'khadar'. Recent experimental evidence confirms the effectiveness of the mentioned plants in ameliorating MS symptoms. Moreover, according to ITM, prolonged exposure to cold and consuming foodstuff with cold temperament might be involved in the etiopathogenesis of MS. CONCLUSIONS: The use of traditional knowledge can help finding neglected risk factors as well as effective and safe therapeutic approaches, phytomedicines and dietary habits for the management of paresthesia and related disorders such as MS. PMID- 26561078 TI - Chlorella vulgaris: A Multifunctional Dietary Supplement with Diverse Medicinal Properties. AB - Chlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteinsChlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteins, omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects., omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects. PMID- 26561079 TI - Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn's Disease and Ulcerative Colitis. AB - Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed. PMID- 26561081 TI - Optics Express review criteria; introducing the novelty and impact statement. AB - In an effort to maintain and improve the quality and importance of papers published, Optics Express has refined its review criteria and instituted a required novelty and impact statement. PMID- 26561080 TI - Continuous glucose monitoring system in the operating room and intensive care unit: any difference according to measurement sites? AB - Given the benefit of glucose control in the perioperative period, we evaluated the accuracy and performance of the continuous glucose monitoring system (CGMS) depending on different measurement sites in the operating room (OR) and in the intensive care unit (ICU). Patients over 18 years of age scheduled for elective surgery and ICU admission were enrolled prospectively. Two CGMS sensors were inserted into the subcutaneous tissue of the proximal lateral thigh and the lateral abdomen. The rate of successful measurements from thigh and abdomen in the OR and in the ICU were calculated separately. Each CGMS values were compared with the time-matched arterial blood glucose measurements. CGMS values from both measurement sites were also compared. A total of 22 patients undergoing cardiac surgeries were studied. The rate of successful measurements was higher in the ICU (73.2 %) than in the OR (66.0 %) (P = 0.01); however, that from thigh (72.9 %) and from abdomen (58.7 %) showed statistically significant difference only in the OR (P = 0.04). The Pearson correlation coefficient of thigh and abdomen versus arterial values was 0.67 and 0.60, respectively (P < 0.001). In Clarke error grid analysis, 94.6 % (89.3 % in the OR and 96.1 % in the ICU) of values from thigh fell into clinically acceptable zones compared to 93.7 % (89.0 % in the OR and 95.4 % in the ICU) from abdomen. There were no statistically significant differences in the accuracy according to measurement sites. The CGMS showed high measurement failure rate, especially in the OR. In the OR, the rate of successful measurement was higher from thigh than from abdomen. The CGMS showed low accuracy compared to arterial reference values. Nevertheless, there was no difference in the accuracy of the CGMS between two measurement sites. Perioperative performance of the CGMS still needs to be improved considering relatively low successful measurement rates. PMID- 26561082 TI - Scattering of a plasmonic nanoantenna embedded in a silicon waveguide. AB - Plasmonic antennas integrated on silicon devices have large and yet unexplored potential for controlling and routing light signals. Here, we present theoretical calculations of a hybrid silicon-metallic system in which a single gold nanoantenna embedded in a single-mode silicon waveguide acts as a resonance driven filter. As a consequence of scattering and interference, when the resonance condition of the antenna is met, the transmission drops by 85% in the resonant frequency band. Firstly, we study analytically the interaction between the propagating mode and the antenna by including radiative corrections to the scattering process and the polarization of the waveguide walls. Secondly, we find the configuration of maximum interaction and numerically simulate a realistic nanoantenna in a silicon waveguide. The numerical calculations show a large suppression of transmission and three times more scattering than absorption, consequent with the analytical model. The system we propose can be easily fabricated by standard silicon and plasmonic lithographic methods, making it promising as real component in future optoelectronic circuits. PMID- 26561083 TI - Amplitude and polarization modulated hyperspectral Stimulated Raman Scattering Microscopy. AB - We present a simple hyperspectral Stimulated Raman Scattering (SRS) microscopy method based on spectral focusing of chirped femtosecond pulses, combined with amplitude (AM) and polarization (PM) modulation. This approach permits the imaging of low concentration components with reduced background signals, combined with good hyperspectral resolution and rapid spectral scanning. We demonstrate, using PM-SRS in a Raman loss configuration, the spectrally resolved detection of deuterated dimethyl sulfoxide (DMSO-d6) at concentrations as low as 0.039 % (5.5 mM). In general, background signals due to cross-phase modulation (XPM), two photon absorption (TPA) and thermal lensing (TL) can reduce the contrast in SRS microscopy. We show that the nonresonant background signal contributing to the SRS signal is, in our case, largely due to XPM. Polarization modulation of the Stokes beam eliminates the nonresonant XPM background, yielding high quality hyperspectral scans at low analyte concentration. The flexibility of our combined AM-PM approach, together with the use of variable modulation frequency and lock in phase, should allow for optimization of SRS imaging in more complex samples. PMID- 26561084 TI - Imaging with partially coherent light: elementary-field approach. AB - Numerical modeling of bright-field and dark-field imaging with spatially partially coherent light is considered. The illuminating field is expressed as a superposition of transversely shifted fully coherent elementary fields of identical form. Examples of imaging under variable coherence conditions demonstrate the computational feasibility of the model even when the coherence area of the illumination is in the wavelength scale. PMID- 26561085 TI - Design of a freeform electronic viewfinder coupled to aberration fields of freeform optics. AB - The newly formulated theory of aberration fields of freeform surfaces describes the aberrations that freeform Zernike polynomial surfaces can correct within folded powered optical systems. This theory has guided the design of an OLED based reflective freeform electronic viewfinder covering a 25 degrees full field of-view with a 12 mm eyebox, which is reported together with a detailed methodology that begins with developing an unobscured starting point and ends with an optimized freeform design, analyzed both in display and visual spaces. In addition, tolerancing of the system points to the potential low sensitivity of these systems to manufacturing tilt (10 arcmin), decenter and despace (100 um), and figure errors (lambda/2 @ 0.632 um). PMID- 26561086 TI - Electrically adjustable location of a projected image in augmented reality via a liquid-crystal lens. AB - An augmented reality (AR) system involving the electrically tunable location of a projected image is implemented using a liquid-crystal (LC) lens. The projected image is either real or virtual. By effectively doubling the LC lens power following light reflection, the position of a projected virtual image can be made to vary from 42 to 360 cm, while the tunable range for a projected real image is from 27 to 52 cm on the opposite side. The optical principle of the AR system is introduced and could be further developed for other tunable focusing lenses, even those with a lower lens power. The benefits of this study could be extended to head-mounted display systems for vision correction or vision compensation. We believe that tunable focusing LC optical elements are promising developments in the thriving field of AR applications. PMID- 26561087 TI - High responsivity SiGe heterojunction phototransistor on silicon photonics platform. AB - We report on a novel near infrared SiGe phototransistor fabricated by a standard silicon photonics foundry. The device is first investigated by simulations. The fabricated devices are characterized in terms of current-voltage characteristics at different optical power. Typical phototransistors exhibit 1.55um record responsivity at low optical power exceeding 232A/W and 42A/W at 5V and 1V bias, respectively. A differential detection scheme is also proposed for the dark current cancellation to significantly increase the device sensitivity. PMID- 26561088 TI - Colloidal superlattices for unnaturally high-index metamaterials at broadband optical frequencies. AB - The recent advance in the assembly of metallic nanoparticles (NPs) has enabled sophisticated engineering of unprecedented light-matter interaction at the optical domain. In this work, I expand the design flexibility of NP optical metamaterial to push the upper limit of accessible refractive index to the unnaturally high regime. The precise control over the geometrical parameters of NP superlattice monolayer conferred the dramatic increase in electric resonance and related effective permittivity far beyond the naturally accessible regime. Simultaneously, effective permeability change, another key factor to achieving high refractive index, was effectively suppressed by reducing the thickness of NPs. By establishing this design rule, I have achieved unnaturally high refractive index (15.7 at the electric resonance and 7.3 at the quasi-static limit) at broadband optical frequencies (100 THz ~300 THz). I also combined this NP metamaterial with graphene to electrically control the high refractive index over the broad optical frequencies. PMID- 26561089 TI - Coherent diffraction imaging of non-isolated object with apodized illumination. AB - Coherent diffraction imaging (CDI) is an established lensless imaging method widely used at the x-ray regime applicable to the imaging of non-periodic materials. Conventional CDI can practically image isolated objects only, which hinders the broader application of the method. We present the imaging of non isolated objects by employing recently proposed "non-scanning" apodized illumination CDI at an optical wavelength. We realized isolated apodized illumination with a specially designed optical configuration and succeeded in imaging phase objects as well as amplitude objects. The non-scanning nature of the method is important particularly in imaging live cells and tissues, where fast imaging is required for non-isolated objects, and is an advantage over ptychography. We believe that our result of phase contrast imaging at an optical wavelength can be extended to the quantitative phase imaging of cells and tissues. The method also provides the feasibility of the lensless single-shot imaging of extended objects with x-ray free-electron lasers. PMID- 26561090 TI - Fast spatial beam shaping by acousto-optic diffraction for 3D non-linear microscopy. AB - Acousto-optic deflection (AOD) devices offer unprecedented fast control of the entire spatial structure of light beams, most notably their phase. AOD light modulation of ultra-short laser pulses, however, is not straightforward to implement because of intrinsic chromatic dispersion and non-stationarity of acousto-optic diffraction. While schemes exist to compensate chromatic dispersion, non-stationarity remains an obstacle. In this work we demonstrate an efficient AOD light modulator for stable phase modulation using time-locked generation of frequency-modulated acoustic waves at the full repetition rate of a high power laser pulse amplifier of 80 kHz. We establish the non-local relationship between the optical phase and the generating acoustic frequency function and verify the system for temporal stability, phase accuracy and generation of non-linear two-dimensional phase functions. PMID- 26561091 TI - Controlling quantum dot emission by plasmonic nanoarrays. AB - Metallic nanoparticle arrays support localized surface plasmon resonances (LSPRs) and propagating surface lattice resonances (SLRs). We study the control of quantum dot (QD) emission coupled to the optical modes of silver nanoparticle arrays, both experimentally and numerically. With a hybrid lithography functionalization method, the QDs are deposited in the vicinity of the nanoparticles. Directionality and enhancement of the emission are observed in photoluminescence spectra and fluorescence lifetime measurements, respectively. Similar features are also demonstrated in the numerical simulations. The tunable emission of this type of hybrid structures could lead to potential applications in light sources. PMID- 26561092 TI - Retrace error reconstruction based on point characteristic function. AB - Figure measuring interferometers generally work in the null condition, i.e., the reference rays share the same optical path with the test rays through the imaging system. In this case, except field distortion error, effect of other aberrations cancels out and doesn't result in measureable systematic error. However, for spatial carrier interferometry and non-null aspheric test cases, null condition cannot be achieved typically, and there is excessive measurement error that is referenced as retrace error. Previous studies about retrace error can be generally distinguished into two categories: one based on 4th-order aberration formalism, the other based on ray tracing through interferometer model. In this paper, point characteristic function (PCF) is used to analyze retrace error in a Fizeau interferometer working in high spatial carrier condition. We present the process of reconstructing retrace error with and without element error in detail. Our results are in contrast with those obtained by ray tracing through interferometer model. The small difference between them (less than 3%) shows that our method is effective. PMID- 26561093 TI - Silicon nanoridge array waveguides for nonlinear and sensing applications. AB - We fabricate and characterize waveguides composed of closely spaced and longitudinally oriented silicon ridges etched into silicon-on-insulator wafers. Through both guided mode and bulk measurements, we demonstrate that the patterning of silicon waveguides on such a deeply subwavelength scale is desirable for nonlinear and sensing applications alike. The proposed waveguide geometry simultaneously exhibits comparable propagation losses to similar schemes proposed in literature, an enhanced effective third-order nonlinear susceptibility, and high sensitivity to perturbations in its environment. PMID- 26561094 TI - Large one-time photo-induced tuning of directional couplers in chalcogenide-on silicon platform. AB - The stable one-time tuning of silicon-photonic directional couplers, over a broad range of coupling ratios, is achieved through the selective photo-removal of an upper cladding layer of chalcogenide glass. Analysis shows that the coupling coefficient per unit length between two parallel fully-etched silicon waveguides may be changed by 45%. The power coupling ratio of a 50 um-long directional coupler between two such waveguides may be tuned arbitrarily between 0 and 1, with weak residual wavelength dependence. Smaller modifications in the coupling coefficient per unit length are obtained between two partially-etched ridge waveguides, on the order of 10%. The proposed procedure is demonstrated in the post-fabrication tuning of transmission notches of a race-track resonator, from over-coupling through critical coupling to weak coupling. The extinction ratio of specific resonances is varied between 4 and 40 dB. The coupling ratio of a tuned device remains stable following three months of storage. PMID- 26561095 TI - Stable closed-loop fiber-optic delay of arbitrary radio-frequency waveforms. AB - Thermal drifts in long fiber-optic delay lines are compensated based on chromatic dispersion. An arbitrary input radio-frequency (RF) waveform and a control RF sine wave modulate two different tunable laser sources and are coupled into the fiber delay line. The RF phase of the control tone at the output of the delay line is monitored and used to adjust the wavelengths of both sources, so that the effects of thermal drifts and dispersion cancel out. The input and control waveforms are separated in the optical domain, and no restrictions are imposed on their RF spectra. A figure of merit is proposed, in terms of the fiber delay, range of temperature changes that may be compensated for, and residual delay variations. An upper bound on performance is established in terms of the specifications of the tunable lasers. The principle is used in the stable distribution of sine waves and of broadband linear frequency-modulated (LFM) waveforms, which are commonly employed in radar systems. Lastly, the method is incorporated in stable interrogation of a localized hot-spot within a high resolution, distributed Brillouin fiber sensing setup. The results demonstrate the applicability of the proposed protocol in the processing of arbitrary waveforms, as part of larger, more complex systems. PMID- 26561096 TI - Ni(2+) doped glass ceramic fiber fabricated by melt-in-tube method and successive heat treatment. AB - Glass ceramic fibers containing Ni(2+) doped LiGa(5)O(8) nanocrystals were fabricated by a melt-in-tube method and successive heat treatment. Fiber precursors were prepared by drawing at high temperature where fiber core glass was melted while fiber clad glass was softened. After heat treatment, LiGa(5)O(8) nanocrystals were precipitated in the fiber core. Excited by 980 nm laser, efficient broadband near-infrared emission was observed in the glass ceramic fiber compared to that of precursor fiber. The melt-in-tube method can realize controllable crystallization and is suitable for fabrication of novel glass ceramic fibers. The Ni(2+)-doped glass ceramic fiber is promising for broadband optical amplification. PMID- 26561097 TI - Flip-chip assembly of VCSELs to silicon grating couplers via laser fabricated SU8 prisms. AB - This article presents the flip-chip bonding of vertical-cavity surface-emitting lasers (VCSELs) to silicon grating couplers (GCs) via SU8 prisms. The SU8 prisms are defined on top of the GCs using non-uniform laser ablation process. The prisms enable perfectly vertical coupling from the bonded VCSELs to the GCs. The VCSELs are flip-chip bonded on top of the silicon GCs employing the laser-induced forward transfer (LIFT)-assisted thermocompression technique. An excess loss of < 1 dB at 1.55 um measured from the bonded assemblies is reported in this paper. The results of high speed transmission experiments performed on the bonded assemblies with clear eye openings up to 20 Gb/s are also presented. PMID- 26561098 TI - Comparison of cost- and energy-efficient signal modulations for next generation passive optical networks. AB - Extensive numerical investigations are undertaken to analyze and compare, for the first time, the performance, techno-economy, and power consumption of three-level electrical Duobinary, optical Duobinary, and PAM-4 modulation formats as candidates for high-speed next-generation PONs supporting downstream 40 Gb/s per wavelength signal transmission over standard SMFs in C-band. Optimization of transceiver bandwidths are undertaken to show the feasibility of utilizing low cost and band-limited components to support next-generation PON transmissions. The effect of electro-absorption modulator chirp is examined for electrical Duobinary and PAM-4. Electrical Duobinary and optical Duobinary are power efficient schemes for smaller transmission distances of 10 km SMFs and optical Duobinary offers the best receiver sensitivity albeit with a relatively high transceiver cost. PAM-4 shows the best power budget and cost-efficiency for larger distances of around 20 km, although it consumes more power. Electrical Duobinary shows the best trade-off between performance, cost and power dissipation. PMID- 26561099 TI - Highly efficient Yb-free Er-La-Al doped ultra-low NA large mode area single trench fiber laser. AB - We demonstrate a 60um core diameter Yb free Er-La-Al doped single-trench fiber having a 0.038 ultra-low-NA, fabricated using conventional MCVD process in conjunction with solution doping technique. Numerical simulations predict an effective single mode operation with effective area varying from 1,820um(2) to 1,960um(2) (taking bend-induced modal distortion into account) for different thicknesses of trenches and resonant rings at a constant bend radius of 25cm. Moreover, all solid structure favors easy cleaving and splicing. Experimental measurements demonstrate a robust effective single mode operation. Furthermore, with a 4%-4% laser cavity, this fiber shows a record efficiency of 46% with respect to the absorbed pump power. PMID- 26561100 TI - Up-converted emission and mode beating in Er(3+)-doped fibers. AB - We demonstrate the differences in the excited state transmission (EST) for different modes in 8 MUm core diameter, Er(3+)- doped silica fiber. The S(2) (Spatially and Spectrally resolved) imaging method was used to determine the modal composition of the transmitted beam and to analyze the group delays of the higher order modes. We register the up-converted emission under two beam excitation (980 nm + 850 nm or 790 nm) and propose the numerical model for the anti-Stokes emission analysis. Taking additionally into account the interference of the beating fiber modes, one can expect the inhomogeneous spatial distribution of the excited ions. This was predicted by numerical calculations. The obtained results have been confirmed by taking photo of the up-converted emission as seen from the side of the fiber. PMID- 26561101 TI - Development of solar-blind photodetectors based on Si-implanted beta-Ga(2)O(3). AB - beta-Ga(2)O(3) films grown on Al(2)O(3) by a metalorganic chemical vapor deposition technique were used to fabricate a solar-blind photodetector with a planar photoconductor structure. The crystal structure and quality of the beta Ga(2)O(3) films were analyzed using X-ray diffraction and micro-Raman spectroscopy. Si ions were introduced into the beta-Ga(2)O(3) thin films by ion implantation method and activated by an annealing process to form an Ohmic contact between the Ti/Au electrode and the beta-Ga(2)O(3) film. The electrical conductivity of the beta-Ga(2)O(3) films was greatly improved by the implantation and subsequent activation of the Si ions. The photoresponse properties of the photodetectors were investigated by analyzing the current-voltage characteristics and the time-dependent photoresponse curves. The fabricated solar-blind photodetectors exhibited photoresponse to 254 nm wavelength, and blindness to 365 nm light, with a high spectral selectivity. PMID- 26561102 TI - Compact, 15 Gb/s electro-optic modulator through carrier accumulation in a hybrid Si/SiO(2)/Si microdisk. AB - High-speed electro-optic modulators are among the key elements in any optical interconnect system. In this work we design and demonstrate an electro-optic modulator based on carrier accumulation on a multilayer integrated photonic platform comprising a stack of high quality Si, SiO(2), and Si layers. The device consists of a 3-MUm radius microdisk with an embedded capacitor. Characterization results reveal an operation bandwidth of exceeding 10 GHz. The device is capable of transmitting 15 Gb/s with the on/off keying format in a single polarization. The proposed structure can be self-trimmed by up to 1 nm in wavelength by applying a dc bias voltage without any power consumption. This feature eliminates the need for power-hungry thermal-based compensation methods to address the resonance wavelength mismatch due to fabrication imperfections. PMID- 26561103 TI - Quantitative test of general theories of the intrinsic laser linewidth. AB - We perform a first-principles calculation of the quantum-limited laser linewidth, testing the predictions of recently developed theories of the laser linewidth based on fluctuations about the known steady-state laser solutions against traditional forms of the Schawlow-Townes linewidth. The numerical study is based on finite-difference time-domain simulations of the semiclassical Maxwell-Bloch lasing equations, augmented with Langevin force terms, and includes the effects of dispersion, losses due to the open boundary of the laser cavity, and non linear coupling between the amplitude and phase fluctuations (alpha factor). We find quantitative agreement between the numerical results and the predictions of the noisy steady-state ab initio laser theory (N-SALT), both in the variation of the linewidth with output power, as well as the emergence of side-peaks due to relaxation oscillations. PMID- 26561104 TI - Amplification of 12 OAM Modes in an air-core erbium doped fiber. AB - We theoretically propose an air-core erbium doped fiber amplifier capable of providing relatively uniform gain for 12 orbital angular momentum (OAM) modes (|L| = 5, 6 and 7, where |L| is the OAM mode order) over the C-band. Amplifier performance under core pumping conditions for a uniformly doped core for each of the supported pump modes (110 in total) was separately assessed. The differential modal gain (DMG) was found to vary significantly depending on the pump mode used, and the minimum DMG was found to be 0.25 dB at 1550 nm provided by the OAM (8,1) pump mode. A tailored confined doping profile can help to reduce the pump mode dependency for core pumped operation and help to increase the number of pump modes that can support a DMG below 1 dB. For the more practical case of cladding pumped operation, where the pump mode dependency is almost removed, a DMG of 0.25 dB and a small signal gain of >20 dB can be achieved for the 12 OAM modes across the full C-band. PMID- 26561105 TI - Anomalous diamagnetic shifts in InP-GaP lateral quantum-wires. AB - Linearly polarized photoluminescence (PL) measurements were carried out on InP GaP lateral nanowires grown using a lateral composition modulation method in pulsed magnetic fields up to ~ 50 T. In these structures, the energy band alignment becomes type-I and type-II in In-rich wire and Ga-rich barrier regions, respectively. It is revealed that the polarization of the type-I PL is oriented along the [110] crystal direction, whereas that of the type-II PL is along the [110] direction in the absence of magnetic field. These two different PL peaks exhibit anomalous energy shifts with respect to the direction of the magnetic field due to the variation of the confined energy in the exciton center of mass potential. PMID- 26561106 TI - Large-stroke convex micromirror actuated by electromagnetic force for optical power control. AB - This paper contributes a novel design and the corresponding fabrication process to research on the unique topic of micro-electro-mechanical systems (MEMS) deformable convex micromirror used for focusing-power control. In this design, the shape of a thin planar metal-coated polymer-membrane mirror is controlled electromagnetically by using the repulsive force between two magnets, a permanent magnet and a coil solenoid, installed in an actuator system. The 5 mm effective aperture of a large-stroke micromirror showed a maximum center displacement of 30.08 um, which enabled control of optical power across a wide range that could extend up to around 20 diopters. Specifically, utilizing the maximum optical power of 20 diopter by applying a maximum controlling current of 0.8 A yielded consumption of at most 2 W of electrical power. It was also demonstrated that this micromirror could easily be integrated in miniature tunable optical imaging systems. PMID- 26561107 TI - Simultaneous type I and type II Cerenkov-phase matched second-harmonic generation in disordered nonlinear photonic structures. AB - We observe simultaneous type I and II Cerenkov-phase matched second-harmonic generation in a disordered nonlinear photonic crystal. The mean width of the disordered ferroelectric domains and the laser beam width are adjusted to be on the same length scale. We analyze the polarization properties, emission angles and intensities of each process. PMID- 26561108 TI - Mode converter based on an inverse taper for multimode silicon nanophotonic integrated circuits. AB - An inverse taper on silicon is proposed and designed to realize an efficient mode converter available for the connection between multimode silicon nanophotonic integrated circuits and few-mode fibers. The present mode converter has a silicon on-insulator inverse taper buried in a 3 * 3MUm(2) SiN strip waveguide to deal with not only for the fundamental mode but also for the higher-order modes. The designed inverse taper enables the conversion between the six modes (i.e., TE(11), TE(21), TE(31), TE(41), TM(11), TM(12)) in a 1.4 * 0.22MUm(2) multimode SOI waveguide and the six modes (like the LP(01), LP(11a), LP(11b) modes in a few mode fiber) in a 3 * 3MUm(2) SiN strip waveguide. The conversion efficiency for any desired mode is higher than 95.6% while any undesired mode excitation ratio is lower than 0.5%. This is helpful to make multimode silicon nanophotonic integrated circuits (e.g., the on-chip mode (de)multiplexers developed well) available to work together with few-mode fibers in the future. PMID- 26561109 TI - Compensation of errors due to incident beam drift in a 3 DOF measurement system for linear guide motion. AB - A measurement system with three degrees of freedom (3 DOF) that compensates for errors caused by incident beam drift is proposed. The system's measurement model (i.e. its mathematical foundation) is analyzed, and a measurement module (i.e. the designed orientation measurement unit) is developed and adopted to measure simultaneously straightness errors and the incident beam direction; thus, the errors due to incident beam drift can be compensated. The experimental results show that the proposed system has a deviation of 1 MUm in the range of 200 mm for distance measurements, and a deviation of 1.3 MUm in the range of 2 mm for straightness error measurements. PMID- 26561110 TI - Broadband unidirectional cloak designed by eikonal theory. AB - A method for designing optical device is derived based on the eikonal theory, which could obtain the eikonal distribution on a curved surface according to the propagation characteristics of the subsequent light wave. Then combining with the phase matching condition, we designed a broadband unidirectional cloak. Different from the reported unidirectional cloaks, the proposed one could be used for coherent wave and has continuous broadband performance. Moreover, it has three cloaked regions. Full-wave simulation results verify the properties of the cloak. PMID- 26561111 TI - Femtoliter-scale optical nanofiber sensors. AB - We report a robust and sensitive optical nanofiber sensor with a femtoliter-scale detection volume. The sensor is fabricated by embedding a 800-nm-diameter nanofiber into a microfluidic chip with probing light propagated perpendicular to a 5-MUm-wide detection channel. To verify the effectiveness of the sensor, we present measurements of fluorescence intensity and refractive index (RI) with detection limits of 1 * 10(-7) M for fluorescein and 2.8 * 10(-4) RIU, respectively. The femtoliter-scale optical nanofiber sensor shown here may provide a compact and versatile sensing platform for sensitive and fast detection of ultra-low-volume samples, as well as studying the dynamics of single molecule. PMID- 26561112 TI - Gerchberg-Saxton-like ghost imaging. AB - Correlation is widely used to reconstruct the object image in ghost imaging (GI). But it only offers a linear proportion of the signal-to-noise ratios (SNR) to the number of measurements. We develop a Gerchberg-Saxton-like technique for GI image reconstruction in this manuscript. The proposed technique takes the advantage of the integral property of the Fourier transform, and treat the captured data as constraints for image reconstruction. We numerically and experimentally demonstrate the technique, and observe a nonlinear growth of the SNR value with respect to the number of measurements in the simulation. The proposed technique provides a different perspective of image reconstruction of GI, and will be beneficial to further explore its potential. PMID- 26561113 TI - 448 Gbit/s, 32 Gbaud 128 QAM coherent transmission over 150 km with a potential spectral efficiency of 10.7 bit/s/Hz. AB - We realized a single-carrier, polarization-multiplexed 32 Gbaud 128 QAM coherent transmission. Digital frequency-domain equalization enabled us to achieve waveform distortion compensation of a wideband data signal with high frequency resolution. Thus, we successfully increased the QAM multiplicity to 128 at 32 Gbaud, and transmitted 448 Gbit/s data over 150 km with a potential spectral efficiency of 10.7 bit/s/Hz. This is the highest multiplicity and spectral efficiency yet achieved in a coherent QAM transmission at a baud rate of as high as 32 Gbaud. PMID- 26561114 TI - Induced dark solitary pulse in an anomalous dispersion cavity fiber laser. AB - We report on the formation of induced dark solitary pulses in a net anomalous dispersion cavity fiber laser. In a weak birefringence cavity fiber laser simultaneous laser oscillation along the two orthogonal polarization directions of the cavity could be achieved. Under suitable conditions bright cavity solitons could be formed along one polarization direction while CW emission occurs along the orthogonal polarization direction. In a previous paper we have shown that under incoherent polarization coupling a bright soliton always induces a broad dark pulse on the CW beam. In the paper we further show that under coherent polarization coupling a bright soliton could further induce either a weak bright or a dark solitary pulse on the bottom of the broad dark pulse. Numerical simulations have also well reproduced the experimental observations, and further show whether a weak dark or bright solitary pulse is induced is determined by the presence or absence of a phase jump in the induced pulse. PMID- 26561115 TI - Stimulated Raman scattering threshold for partially coherent light in silica fibers. AB - Stimulated Raman scattering (SRS) is an important limiting factor for achieving high peak power intensity in fiber amplifier systems. It was proposed to use partially coherent light to increase the SRS threshold significantly. In this paper, the SRS threshold of partially coherent light in silica fibers is investigated by both experiments and theoretical analysis, which show that the SRS threshold is independent on light coherency when the bandwidth of the light is much narrower than 30 nm. PMID- 26561116 TI - Efficient modal analysis using compressive optical interferometry. AB - Interferometry is routinely used for spectral or modal analysis of optical signals. By posing interferometric modal analysis as a sparse recovery problem, we show that compressive sampling helps exploit the sparsity of typical optical signals in modal space and reduces the number of required measurements. Instead of collecting evenly spaced interferometric samples at the Nyquist rate followed by a Fourier transform as is common practice, we show that random sampling at sub Nyquist rates followed by a sparse reconstruction algorithm suffices. We demonstrate our approach, which we call compressive interferometry, numerically in the context of modal analysis of spatial beams using a generalized interferometric configuration. Compressive interferometry applies to widely used optical modal sets and is robust with respect to noise, thus holding promise to enhance real-time processing in optical imaging and communications. PMID- 26561118 TI - Robustness and spatial multiplexing via diffractal architectures. AB - When plane waves diffract through fractal-patterned apertures, the resulting far field profiles or diffractals also exhibit iterated, self-similar features. Here we show that this specific architecture enables robust signal transmission and spatial multiplexing: arbitrary parts of a diffractal contain sufficient information to recreate the entire original sparse signal. PMID- 26561119 TI - Interferogram conditioning for improved Fourier analysis and application to X-ray phase imaging by grating interferometry. AB - An interferogram conditioning procedure, for subsequent phase retrieval by Fourier demodulation, is presented here as a fast iterative approach aiming at fulfilling the classical boundary conditions imposed by Fourier transform techniques. Interference fringe patterns with typical edge discontinuities were simulated in order to reveal the edge artifacts that classically appear in traditional Fourier analysis, and were consecutively used to demonstrate the correction efficiency of the proposed conditioning technique. Optimization of the algorithm parameters is also presented and discussed. Finally, the procedure was applied to grating-based interferometric measurements performed in the hard X-ray regime. The proposed algorithm enables nearly edge-artifact-free retrieval of the phase derivatives. A similar enhancement of the retrieved absorption and fringe visibility images is also achieved. PMID- 26561117 TI - Accurate determination of segmented X-ray detector geometry. AB - Recent advances in X-ray detector technology have resulted in the introduction of segmented detectors composed of many small detector modules tiled together to cover a large detection area. Due to mechanical tolerances and the desire to be able to change the module layout to suit the needs of different experiments, the pixels on each module might not align perfectly on a regular grid. Several detectors are designed to permit detector sub-regions (or modules) to be moved relative to each other for different experiments. Accurate determination of the location of detector elements relative to the beam-sample interaction point is critical for many types of experiment, including X-ray crystallography, coherent diffractive imaging (CDI), small angle X-ray scattering (SAXS) and spectroscopy. For detectors with moveable modules, the relative positions of pixels are no longer fixed, necessitating the development of a simple procedure to calibrate detector geometry after reconfiguration. We describe a simple and robust method for determining the geometry of segmented X-ray detectors using measurements obtained by serial crystallography. By comparing the location of observed Bragg peaks to the spot locations predicted from the crystal indexing procedure, the position, rotation and distance of each module relative to the interaction region can be refined. We show that the refined detector geometry greatly improves the results of experiments. PMID- 26561120 TI - High-intracavity-power thin-disk laser for the alignment of molecules. AB - We propose a novel approach for strong alignment of gas-phase molecules for experiments at arbitrary repetition rates. A high-intracavity-power continuous wave laser will provide the necessary ac electric field of 10(10)-10(11) W/cm(2). We demonstrate thin-disk lasers based on Yb:YAG and Yb:Lu(2)O(3) in a linear high finesse resonator providing intracavity power levels in excess of 100 kW at pump power levels on the order of 50 W. The multi-longitudinal-mode operation of this laser avoids spatial-hole burning even in a linear standing-wave resonator. The system will be scaled up as in-vacuum system to allow for the generation of fields of 10(11) W/cm(2). This system will be directly applicable for experiments at modern X-ray light sources, such as synchrotrons or free-electron lasers, which operate at various very high repetition rates. This would allow to record molecular movies through temporally resolved diffractive imaging of fixed-in space molecules, as well as the spectroscopic investigation of combined X-ray-NIR strong-field effects of atomic and molecular systems. PMID- 26561121 TI - TRACK--A new method for the evaluation of low-level extinction coefficient in optical films. AB - We develop a rigorous methodology named TRACK based on the collection of multi angle spectrophotometric transmission and reflection data in order to assess the extinction coefficient of quasi-transparent optical films. The accuracy of extinction coefficient values obtained by this method is not affected by sample non-idealities (thickness non-uniformity, refractive index inhomogeneities, anisotropy, interfaces, etc.) and therefore a simple two-layer (substrate/film) optical model can be used. The method requires the acquisition of transmission and reflection data at two angles of incidence: 10 degrees and 65 degrees in p polarization. Data acquired at 10 degrees provide information about the film thickness and the refractive index, while data collected at 65 degrees are used for absorption evaluation and extinction coefficient computation. We test this method on three types of samples: (i) a CR-39 plastic substrate coated with a thick protective coating; (ii) the same substrate coated with a thin TiO(2) film; (iii) and a thick Si(3)N(4) film deposited on Gorilla glass that presents thickness non-uniformity and refractive index gradient non-idealities. We also compare absorption and extinction coefficient values obtained at 410 and 550 nm by both TRACK and Laser Induced Deflection techniques in the case of a 1 micron thick TiO(2) coating. Both methods display consistent extinction coefficient values in the 10(-4) and 10(-5) ranges at 410 and 550 nm, respectively, which proves the validity of the methodology and provides an estimate of its accuracy limit. PMID- 26561122 TI - Spectral characteristics of terahertz radiation from plasmonic photomixers. AB - We present a comprehensive analysis of spectral characteristics of terahertz radiation from plasmonic photomixers. We fabricate plasmonic photomixer prototypes with plasmonic contact electrode gratings on a low temperature grown GaAs substrate and characterize the spectral properties of the generated terahertz radiation by use of a heterodyne detection scheme. Our analysis shows that linewidth, stability, and frequency tuning range of the generated terahertz radiation are directly determined by linewidth, stability, and wavelength tuning range of optical pump beam and not affected by device geometry, substrate properties, optical pump power level and other operational settings. Our study indicates the crucial role of optical sources in realizing high performance terahertz spectroscopy and wireless communication systems based on plasmonic photomixers. PMID- 26561123 TI - Free-space beam shaping for precise control and conversion of modes in optical fiber. AB - We consider the general problem of free-space beam shaping for coupling in and out of higher order modes (HOMs) in optical fibers with high purity and low loss. We compare the performance of two simple phase structures - binary phase plates (BPPs) and axicons - for converting Gaussian beams to HOMs and vice versa. Both axicons and BPPs allow for excitation of modes with high purity (>15 dB parasitic mode suppression), or conversion of HOMs to near-Gaussian beams (M2 < 1.25). Axicon coupling in single-clad fibers allows for lower loss (0.85 +/- 0.1 dB) conversion than BPPs (1.7 +/- 0.1 dB); but BPPs are compatible with any fiber design, and allow for rapid switching between modes. The experiments detailed here use all commercial components and fibers, allowing for a simple means to investigate the unique properties of multi-mode fibers. PMID- 26561124 TI - Nonblocking Clos networks of multiple ROADM rings for mega data centers. AB - Optical networks have been introduced to meet the bandwidth requirement of mega data centers (DC). Most existing approaches are neither scalable to face the massive growth of DCs, nor contention-free enough to provide full bisection bandwidth. To solve this problem, we propose two symmetric network structures: ring-MEMS-ring (RMR) network and MEMS-ring-MEMS (MRM) network based on classical Clos theory. New strategies are introduced to overcome the additional wavelength constraints that did not exist in the traditional Clos network. Two structures that followed the strategies can enable high scalability and nonblocking property simultaneously. The one-to-one correspondence of the RMR and MRM structures to a Clos is verified and the nonblocking conditions are given along with the routing algorithms. Compared to a typical folded-Clos network, both structures are more readily scalable to future mega data centers with 51200 racks while reducing number of long cables significantly. We show that the MRM network is more cost effective than the RMR network, since the MRM network does not need tunable lasers to achieve nonblocking routing. PMID- 26561125 TI - Bessel-like beam array formation by periodical arrangement of the polymeric round tip microstructures. AB - Here, we report the formation of Bessel-like beam array from periodic patterns fabricated by the four-beam interference lithography. Characteristics of the generated Bessel-like beams depend on geometrical parameters of the fabricated microaxicon-like structures, which can be easily controlled via the laser processing parameters. The output beam characteristics disclose the attributes of Bessel beams. The demonstrated method enables an easy fabrication of angular tolerant wavefront detectors, optical tweezers, optical imaging systems or materials processing tools, having a broad range of applications. PMID- 26561126 TI - Guided-mode-resonance-enhanced measurement of thin-film absorption. AB - We present a numerical and experimental study of a guided-mode-resonance (GMR) device for detecting surface-bound light-absorbing thin films. The GMR device functions as an optical resonator at the wavelength strongly absorbed by the thin film. The GMR mode produces an evanescent field that results in enhanced optical absorption by the thin film. For a 100-nm-thick lossy thin film, the GMR device enhances its absorption coefficients over 26 * compared to a conventional glass substrate. Simulations show the clear quenching effect of the GMR when the extinction coefficient is greater than 0.01. At the resonant wavelength, the reflectance of the GMR surface correlates well with the degree of optical absorption. GMR devices are fabricated on a glass substrate using a surface relief grating and a titanium-dioxide coating. To analyze a visible absorbing dye, the reflection coefficient of dye-coated GMR devices was measured. The GMR based method was also applied to detecting acid gases, such as hydrochloric vapor, by monitoring the change in absorption in a thin film composed of a pH indicator, bromocresol green. This technique potentially allows absorption analysis in the visible and infrared ranges using inexpensive equipment. PMID- 26561127 TI - Parametric characterization of surface plasmon polaritons at a lossy interface. AB - Using exact solutions of Maxwell's equations, we investigate the evolution of the transversal profile of a surface plasmon polariton (SPP) packet propagating along a planar interface between a dielectric and a lossy metal. We introduce a parameter to measure the propagation length of the SPP packet and analyze its behavior with respect to the shape of the packet and the dielectric characteristics of the interface. Furthermore, we study the polarization properties of the SPP packet and define two parameters to quantify the fraction of the irradiance contained in the s- and p-polarization components of the associated field. Our results help to advance in the understanding of the SPP optics beyond the single-mode description. PMID- 26561128 TI - Surface-enhanced terahertz spectroscopy using gold rod structures resonant with terahertz waves. AB - Terahertz (THz) spectroscopy is a promising method to measure the spectrum of low frequency modes of molecules or ensembles, such as crystals and polymers, including proteins. However, the main drawback of THz spectroscopy is its extremely low sensitivity. In the present study, we report on signal enhancement in THz spectroscopy achieved by depositing amino acid molecules or their derivatives on a gold rod structured silicon substrate whose localized surface plasmon resonance is exhibited in the THz frequency region. The distinct peaks derived from the enhancement of the inherent spectrum based on a molecular crystal were clearly observed when a longitudinal plasmon resonance mode of the gold rod structure was excited and the plasmon resonance band overlapped the molecular/intermolecular vibrational mode. We discuss the mechanism by which surface-enhanced THz spectroscopy was induced from the viewpoint of the enhancement of light-matter coupling due to plasmon excitation and the modulation of the plasmon band by dipole coupling between the plasmon dipole and molecular/intermolecular vibrational modes. PMID- 26561129 TI - New ultrasensitive resonant photonic platform for label-free biosensing. AB - A multi-analyte biosensing platform with ultra-high resolution ( = 0.2 ng/mL), which is appropriate for the detection in the human serum of a wide range of biomarkers, e.g. those allowing the lung cancer early diagnosis, has been designed. The platform is based on a new configuration of planar ring resonator. The very strong light-matter interaction enabled by the micro-cavity allows a record limit-of-detection of 0.06 pg/mm(2), five times better than the state-of the-art. The device with footprint = 2,200 MUm(2) for each ring, due to its features, has the potential to be integrated in lab-on-chip microsystems for large-scale screenings of people with high risk of developing cancer. PMID- 26561130 TI - Stress manipulated coating for fabricating lightweight X-ray telescope mirrors. AB - In this paper wepresent a method to correct the surface profile of an X-ray mirror by using a stress manipulated coating on the back side of mirror shells. The ability to fabricate a thin walled mirror by some replication process is required if future affordable X-ray space missions are to have ~30 times the effective area of the current best X-ray observatory, i.e., the Chandra X-ray Observatory (CXO). Thus, some process is necessary for using replicated X-ray optics to make the next generation X-ray observatory. However, although the surface roughness of sub-100 MUm length scales can be replicated, no known replication technique can make 1 arc-second or better CXO-like optics. Yet, because the images produced by the CXO are so exquisite, many X-ray astronomers are not willing to settle for less in the future. Therefore, a post replication technique must be developed to make future major X-ray astronomy missions possible. In this paper, we describe a technique based on DC magnetron sputtering. For figure correction, we apply a controlled bias voltage on the surface during the sputtering. We show that we can produce, in 1-D, shape changes large enough (1 MUm over 10 mm) to correct the typical figure errors in replicated optics. We demonstrate reproducibility on an order of 0.6%, and stability over weeks on a scale of less than 1 MUm over 10 mm. For these tests, we used 200 MUm thick pieces of D263 Schott glass, about 5 mm x 20 mm. In addition to the basic concept of controlling the stress with the coating, we describe a new optimization software design to calculate the stress distribution for a desired surface profile. We show that the combination of the stress optimization software coupled with the coating process, can reduce the slope error of a 5 mm x 20 mm glass sample by a factor of ten. PMID- 26561131 TI - Revisiting the comparison between the Shack-Hartmann and the pyramid wavefront sensors via the Fisher information matrix. AB - Exoplanet direct imaging with large ground based telescopes requires eXtreme Adaptive Optics that couples high-order adaptive optics and coronagraphy. A key element of such systems is the high-order wavefront sensor. We study here several high-order wavefront sensing approaches, and more precisely compare their sensitivity to noise. Three techniques are considered: the classical Shack Hartmann sensor, the pyramid sensor and the recently proposed LIFTed Shack Hartmann sensor. They are compared in a unified framework based on precise diffractive models and on the Fisher information matrix, which conveys the information present in the data whatever the estimation method. The diagonal elements of the inverse of the Fisher information matrix, which we use as a figure of merit, are similar to noise propagation coefficients. With these diagonal elements, so called "Fisher coefficients", we show that the LIFTed Shack Hartmann and pyramid sensors outperform the classical Shack-Hartmann sensor. In photon noise regime, the LIFTed Shack-Hartmann and modulated pyramid sensors obtain a similar overall noise propagation. The LIFTed Shack-Hartmann sensor however provides attractive noise properties on high orders. PMID- 26561132 TI - Characterisation of random DFB Raman laser amplifier for WDM transmission. AB - We perform a full numerical characterisation of half-open cavity random DFB Raman fibre laser amplifier schemes for WDM transmission in terms of signal power variation, noise and nonlinear impairments, showcasing the excellent potential of this scheme to provide amplification for DWDM transmission with very low gain variation. PMID- 26561133 TI - Remote electrical arc suppression by laser filamentation. AB - We investigate the interaction of narrow plasma channels formed in the filamentation of ultrashort laser pulses, with a DC high voltage. The laser filaments prevent electrical arcs by triggering corona that neutralize the high voltage electrodes. This phenomenon, that relies on the electric field modulation and free electron release around the filament, opens new prospects to lightning and over-voltage mitigation. PMID- 26561134 TI - Modeling of strain-induced Pockels effect in Silicon. AB - We propose a theoretical model to describe the strain-induced linear electro optic (Pockels) effect in centro-symmetric crystals. The general formulation is presented and the specific case of the strained silicon is investigated in detail because of its attractive properties for integrated optics. The outcome of this analysis is a linear relation between the second order susceptibility tensor and the strain gradient tensor, depending generically on fifteen coefficients. The proposed model greatly simplifies the description of the electro-optic effect in strained silicon waveguides, providing a powerful and effective tool for design and optimization of optical devices. PMID- 26561135 TI - Self-referenced biosensor based on thin dielectric grating combined with thin metal film. AB - Surface plasmon resonance biosensors based on grating coupling exhibiting two plasmons are less known because usually thick gratings and thick metal films are used. In this paper we show that when thin dielectric grating is used on top of thin metal film two surface plasmons are generated at the two boundaries of the metal film represented as two dips in the reflectivity or peaks in the absorption. One of the plasmons is sensitive to the analyte refractive index (sensitivity 580nm/RIU) while the other is sensitive to the refractive index of the substrate; hence it can be used as a reference. This self-reference makes the measurement more accurate and less sensitive to temperature fluctuations and optomechanical drifts. Field distribution calculations show that the plasmon excited at the metal-substrate interface is a long range plasmon with large penetration depth. PMID- 26561136 TI - High-power near-infrared linearly-polarized supercontinuum generation in a polarization-maintaining Yb-doped fiber amplifier. AB - We report an all-fiber linearly-polarized (LP) supercontinuum (SC) source with high average power generated in a polarization-maintaining (PM) master oscillation power-amplifier (MOPA). The experimental configuration comprises an LP picosecond pulsed laser and three PM Yd-doped fiber amplifiers (YDFA). The output has the average power of 124.8 W with the spectrum covering from 850 to 1900 nm. The measured polarization extinction ratio (PER) of the whole SC source is about 85% which verifies the SC an LP source. This work is, to our best knowledge, the highest output average power of an LP SC source that ever reported. The influence of PM fiber splicing method on the LP SC property is investigated by splicing the PM fibers with slow axis parallel or perpendicularly aligned, and also an LP SC with low output power is demonstrated. PMID- 26561137 TI - Experimental demonstration of single-shot phase imaging with a coded aperture. AB - We experimentally demonstrated single-shot phase imaging with a coded aperture (SPICA), which connects digital holography and coherent diffractive imaging based on compressive sensing to realize the advantages of both methods simultaneously. SPICA allows the observation of a complex field with a simple, single-shot optical setup that does not need reference light and does not suffer from losses associated with the field-of-view and spatial resolution. Experiments showed the promising capabilities of SPICA for single-shot holographic imaging. PMID- 26561138 TI - WS(2)/fluorine mica (FM) saturable absorbers for all-normal-dispersion mode locked fiber laser. AB - The report firstly propose a new WS(2) absorber based on fluorine mica (FM) substrate. The WS(2) material was fabricated by thermal decomposition method. The FM was stripped into one single layer as thin as 20 MUm and deposited WS(2) on it, which can be attached to the fiber flank without causing the laser deviation. Similar to quartz, the transmission rate of FM is as high as 90% at near infrared wavelength from one to two micrometers. Furthermore, FM is a highly elastic material so that it is not easy to break off even its thickness was only 20 MUm. On the contrary, quartz is hard to be processed and easy to break off when its thickness is less than 100 MUm. Compared to organic matrix such as polyvinyl alcohol (PVA), FM has higher softening temperature, heat dissipation and laser damage threshold than those of organic composites. In our work, the modulation depth (MD) and non-saturable losses (NLs) of this kind of saturable absorber were measured to be 5.8% and 14.8%, respectively. The WS(2)/FM absorber has a high damage threshold of 406 MW/cm(2), two times higher than that of WS(2)/PVA. By incorporating the saturable absorber into Yb-doped fiber laser cavity, a mode locked fiber laser was achieved with central wavelength of 1052.45 nm. The repetition rate was 23.26 MHz and the maximum average output power was 30 mW. The long term stability of working was proved to be good too. The results indicate that WS(2)/FM film is a practical nonlinear optical material for photonic applications. PMID- 26561139 TI - Highly efficient narrow-band green and red phosphors enabling wider color-gamut LED backlight for more brilliant displays. AB - In this contribution, we propose to combine both narrow-band green (beta sialon:Eu(2+)) and red (K(2)SiF(6):Mn(4+)) phosphors with a blue InGaN chip to achieve white light-emitting diodes (wLEDs) with a large color gamut and a high efficiency for use as the liquid crystal display (LCD) backlighting. beta sialon:Eu(2+), prepared by a gas-pressure sinteing technique, has a peak emission at 535 nm, a full width at half maximum (FWHM) of 54 nm, and an external quantum efficiency of 54.0% under the 450 nm excitation. K(2)SiF(6):Mn(4+) was synthesized by a twe-step co-precipitation methods, and exhibits a sharp line emission spectrum with the most intensified peak at 631 nm, a FWHM of ~3 nm, and an external quantum efficiency of 54.5%. The prepared three-band wLEDs have a high color temperature of 11,184 - 13,769 K (i.e., 7,828 - 8,611 K for LCD displays), and a luminous efficacy of 91 - 96 lm/W, measured under an applied current of 120 mA. The color gamut defined in the CIE 1931 and CIE 1976 color spaces are 85.5 - 85.9% and 94.3 - 96.2% of the NTSC stanadard, respectively. These optical properties are better than those phosphor-cpnverted wLED backlights using wide-band green or red phosphoprs, suggesting that the two narrow-band phosphors investigated are the most suitable luminescent materials for achieving more bright and vivid displays. PMID- 26561140 TI - Specular and antispecular light beams. AB - We consider a class of spatially partially coherent light beams, which are generated by passing a Gaussian Schell-model beam though a wavefront-folding interferometer. In certain cases these beams are shape-invariant on propagation and can exhibit sharp internal structure with a central peak (specular beam) or a central dip (antispecular beam) whose dimensions depend on the spatial coherence area. Such beams are demonstrated experimentally and their cross-like distributions of the complex degree of spatial coherence are measured with a digital micromirror device. PMID- 26561141 TI - Universal ultrafast detector for short optical pulses based on graphene. AB - Graphene has unique optical and electronic properties that make it attractive as an active material for broadband ultrafast detection. We present here a graphene based detector that shows 40-picosecond electrical rise time over a spectral range that spans nearly three orders of magnitude, from the visible to the far infrared. The detector employs a large area graphene active region with interdigitated electrodes that are connected to a log-periodic antenna to improve the long-wavelength collection efficiency, and a silicon carbide substrate that is transparent throughout the visible regime. The detector exhibits a noise equivalent power of approximately 100 uW.Hz(-1/2) and is characterized at wavelengths from 780 nm to 500 um. PMID- 26561142 TI - Optical modulation of aqueous metamaterial properties at large scale. AB - Dynamical control of metamaterials by adjusting their shape and structures has been developed to achieve desired optical functionalities and to enable modulation and selection of spectra responses. However it is still challenging to realize such a manipulation at large scale. Recently, it has been shown that the desired high (or low) symmetry metamaterials structure in solution can be self assembled under external light stimuli. Using the this approach, we systematically investiagted the optical controlling process and report here a dynamical manipulation of magnetic properties of metamaterials. Under external laser excitations, we demonstrated that selected magnetic properties of metamaterials can be tuned with the freedom of chosen wavelength ranges. The magnetic dipole selectivity and tunability were further quantified by in situ spectral measurement. PMID- 26561143 TI - Hyperspectral imaging with a liquid crystal polarization interferometer. AB - A novel hyperspectral imaging system has been developed that takes advantage of the tunable path delay between orthogonal polarization states of a liquid crystal variable retarder. The liquid crystal is placed in the optical path of an imaging system and the path delay between the polarization states is varied, causing an interferogram to be generated simultaneously at each pixel. A data set consisting of a series of images is recorded while varying the path delay; Fourier transforming the data set with respect to the path delay yields the hyperspectral data-cube. The concept is demonstrated with a prototype imager consisting of a liquid crystal variable retarder integrated into a commercial 640x480 pixel CMOS camera. The prototype can acquire a full hyperspectral data-cube in 0.4 s, and is sensitive to light over a 400 nm to 1100 nm range with a dispersion-dependent spectral resolution of 450 cm(-1) to 660 cm(-1). Similar to Fourier transform spectroscopy, the imager is spatially and spectrally multiplexed and therefore achieves high optical throughput. Additionally, the common-path nature of the polarization interferometer yields a vibration-insensitive device. Our concept allows for the spectral resolution, imaging speed, and spatial resolution to be traded off in software to optimally address a given application. The simplicity, compactness, potential low cost, and software adaptability of the device may enable a disruptive class of hyperspectral imaging systems with a broad range of applications. PMID- 26561144 TI - Extraordinary light absorptance in graphene superlattices. AB - Extraordinary absorption decrease in graphene superlattices in the visible range is presented. Due to competition between loss and resonant reflection at resonance, the absorption displays non-monotonic behavior. As the period number increases above a certain critical value, absorption decreases with the increase in the period number. This is in contrast to ordinary absorption for a non resonant condition, which monotonically increases with the period number. Moreover, this extraordinary property can also be controlled by applying a gate voltage to graphene sheets. The results provide not only a new understanding of graphene physics but also an application in nanophotonics and optoelectronics. PMID- 26561145 TI - Mechanism of solitary wave breaking phenomenon in dissipative soliton fiber lasers. AB - We numerically and experimentally investigate the pulse evolution to the edge of destabilization against pumping powers in a strongly dissipative-dispersive laser configuration mode locked by nonlinear polarization evolution (NPE) technique. Two distinct dynamic processes are indicated by numerical results and further evidenced by experimental observations, where one depicts the monotonous increase in peak power and slight narrowing of duration, the other is different in exhibiting obvious broadening in temporal domain. Correspondingly, it is demonstrated in the simulation of cavity dynamics that the artificial saturable absorber plays two opposite roles in pulse shaping, which implies the switch of cavity feedback. Mechanisms with respect to different cavity feedbacks are analyzed based on a newly-proposed theoretical viewpoint, for positive feedback single pulse operation is restricted by the limit of peak power mainly dependent of the gain bandwidth; for negative feedback the breakup is attributed to the limited strength of clamping effect determined by multiple ingredients. PMID- 26561146 TI - Fabrication of conducting-filament-embedded indium tin oxide electrodes: application to lateral-type gallium nitride light-emitting diodes. AB - A novel conducting filament (CF)-embedded indium tin oxide (ITO) film is fabricated using an electrical breakdown method. To assess the performance of this layer as an ohmic contact, it is applied to GaN (gallium nitride) light emitting diodes (LEDs) as a p-type electrode for comparison with typical GaN LEDs using metallic ITO. The operating voltage and output power of the LED with the CF embedded ITO are 3.93 V and 8.49 mW, respectively, at an injection current of 100 mA. This is comparable to the operating voltage and output power of the conventionally fabricated LEDs using metallic ITO (3.93 V and 8.43 mW). Moreover, the CF-ITO LED displays uniform and bright light emission indicating excellent current injection and spreading. These results suggest that the proposed method of forming ohmic contacts is at least as effective as the conventional method. PMID- 26561147 TI - Anomalous index modulations in electrooptic KTa(1-x)Nb(x)O(3) single crystals in relation to electrostrictive effect. AB - KTa(1-x)Nb(x)O(3) is known for its huge Kerr effect, which is a second order electrooptic (EO) effect. By utilizing the large refractive index change Deltan of this EO effect, a fast optical beam deflector has been realized. However, anomalous spatial distributions of Deltan were observed with this beam deflector. This anomaly is ascribed to distortions caused by the electrostrictive effect that occurs when voltage is applied. We assumed a spheric distortion and used a variational method to deduce an analytic solution for the strains that accompany this distortion. The analytic solution coincides with numerical results obtained with the finite element method. In addition, the solution agrees well with the experimentally obtained Deltan distribution. PMID- 26561148 TI - CW-pumped telecom band polarization entangled photon pair generation in a Sagnac interferometer. AB - Polarization entangled photon pair source is widely used in many quantum information processing applications such as teleportation, quantum communications, quantum computation and high precision quantum metrology. We report on the generation of a continuous-wave pumped 1550 nm polarization entangled photon pair source at telecom wavelength using a type-II periodically poled KTiOPO(4) (PPKTP) crystal in a Sagnac interferometer. Hong-Ou-Mandel (HOM) interference measurement yields signal and idler photon bandwidth of 2.4 nm. High quality of entanglement is verified by various kinds of measurements, for example two-photon interference fringes, Bell inequality and quantum states tomography. The source can be tuned over a broad range against temperature or pump power without loss of visibilities. This source will be used in our future experiments such as generation of orbital angular momentum entangled source at telecom wavelength for quantum frequency up-conversion, entanglement based quantum key distributions and many other quantum optics experiments at telecom wavelengths. PMID- 26561149 TI - Nonadiabatic tunnel ionization in strong circularly polarized laser fields: counterintuitive angular shifts in the photoelectron momentum distribution. AB - We perform time-dependent calculation of strong-field ionization of neon, initially prepared in 2p(-1) and 2p(+1) states, with intense near-circularly polarized laser pulses. By solving the three-dimensional time-dependent Schrodinger equation, we find clear different offset angles of the maximum in the photoelectron momentum distribution in the polarization plane of the laser pulses for the two states. We provide clear interpretation that this different angular offset is linked to the sign of the magnetic quantum number, thus it can be used to map out the orbital angular momentum of the initial state. Our results provide a potential tool for studying orbital symmetry in atomic and molecular systems. PMID- 26561150 TI - Unidirectional scattering by nanoparticles near substrates: generalized Kerker conditions. AB - Starting from a general description of light scattering by a nanoparticle in homogeneous surroundings and situated near a substrate, we outline the connection to multipole expansion of scattered light and derive conditions and limits on achievable half-space scattering asymmetry, including the possibility of unidirectional scattering along the propagation direction of the incident light (i.e., generalized Kerker conditions). As a way of realizing strongly asymmetric scattering, we perform a parametric study of the optical properties of disk shaped gap-surface plasmon (GSP) resonators, consisting of a glass spacer sandwiched between two gold disks, with numerical calculations that corroborate the conditions derived from the multipole expansion. Finally, we present proof-of principle experiments of asymmetric scattering by GSP-resonators on a glass substrate. PMID- 26561151 TI - Polarization-dependent aluminum metasurface operating at 450 nm. AB - We report on a polarization-dependent plasmonic aluminum-based high-density metasurface operating at blue wavelengths. The fabricated sub-wavelength structures, tailored in size and geometry, possess strong, localized, plasmonic resonances able to control linear polarization. Best performance is achieved by rotating an elongated rectangular structure of length 180 nm and width 110 nm inside a square lattice of period 250 nm. In the case of 45 degrees rotation of the structure with respect to the lattice, the normal-incidence reflectance drops around the resonance wavelength of 457 nm from about 60 percent to below 2 percent. PMID- 26561152 TI - Spectrally resolved Hong-Ou-Mandel interference between independent photon sources. AB - Hong-Ou-Mandel (HOM) interference between independent photon sources (HOMI-IPS) is the fundamental block for quantum information processing. All the previous HOMI-IPS experiments were carried out in time-domain, however, the spectral information during the interference was omitted. Here, we investigate the HOMI IPS in spectral domain using the recently developed fast fiber spectrometer, and demonstrate the spectral distribution during the HOM interference between two heralded single-photon sources, and two thermal sources. This experiment not only can deepen our understanding of HOMI-IPS from the viewpoint of spectral domain, but also presents a tool to test the theoretical predictions of HOMI-IPS using spectrally engineered sources. PMID- 26561153 TI - Ultra-sparse dielectric nanowire grids as wideband reflectors and polarizers. AB - Engaging both theory and experiment, we investigate resonant photonic lattices in which the duty cycle tends to zero. Corresponding dielectric nanowire grids are mostly empty space if operated as membranes in vacuum or air. These grids are shown to be effective wideband reflectors with impressive polarizing properties. We provide computed results predicting nearly complete reflection and attendant polarization extinction in multiple spectral regions. Experimental results with Si nanowire arrays with 10% duty cycle show ~200-nm-wide band of high reflection for one polarization state and free transmission for the orthogonal state. These results agree quantitatively with theoretical predictions. It is fundamentally extremely significant that the wideband spectral expressions presented can be generated in these minimal systems. PMID- 26561154 TI - Improved axial trapping with holographic optical tweezers. AB - Conventional optical tweezers suffer from several complications when applying axial forces to surface-tethered molecules. Aberrations from the refractive-index mismatch between an oil-immersion objective's medium and the aqueous trapping environment both shift the trap centre and degrade the trapping strength with focal depth. Furthermore, interference effects from back-scattered light make it difficult to use back-focal-plane interferometry for high-bandwidth position detection. Holographic optical tweezers were employed to correct for aberrations to achieve a constant axial stiffness and modulate artifacts from backscattered light. Once the aberrations are corrected for, the trap height can be precisely determined from either the back-scattered light or Brenner's formula. PMID- 26561155 TI - Effect of finite metallic grating size on Rayleigh anomaly-surface plasmon polariton resonances. AB - Rayleigh anomalies (RAs) and surface plasmon polaritons (SPPs) on subwavelength metallic gratings play pivotal roles in many interesting phenomena such as extraordinary optical transmission. In this work, we present a theoretical analysis of the effect of finite metallic grating size on RA-SPP resonances based on the combination of rigorous coupled wave analysis and finite aperture diffraction. One-dimensional arrays of gold subwavelength gratings with different device sizes were fabricated and the optical transmission spectra were measured. As the grating size shrinks, the broadening of the RA-SPP resonances is predicted by the theoretical model. For the first order RA-SPP resonances, the results from this model are in good agreement with the spectra measured from the fabricated plasmonic gratings. PMID- 26561156 TI - Phase retrieval and diffractive imaging based on Babinet's principle and complementary random sampling. AB - We proposed an iterative method for phase retrieval and diffractive imaging based on Babinet's principle and complementary random sampling (CRS). We demonstrated that the whole complex amplitude (not sieved) of an object wave can be accurately retrieved from the diffraction intensities of the object wave sampled by a group of binary CRS masks and the diffractive imaging for the object can be realized through a single digital inverse diffraction. Some experimental results are given for the demonstration. Our experimental results reveal that, using CRS, the influence of a binary random sampling mask on the retrieved field can be well eliminated, and the accuracy and efficiency of the phase retrieval can be greatly improved. PMID- 26561157 TI - Racetrack resonator as a loss measurement platform for photonic components. AB - This work represents the first complete analysis of the use of a racetrack resonator to measure the insertion loss of efficient, compact photonic components. Beginning with an in-depth analysis of potential error sources and a discussion of the calibration procedure, the technique is used to estimate the insertion loss of waveguide width tapers of varying geometry with a resulting 95% confidence interval of 0.007 dB. The work concludes with a performance comparison of the analyzed tapers with results presented for four taper profiles and three taper lengths. PMID- 26561158 TI - Q-factor limits for far-field detection of whispering gallery modes in active microspheres. AB - This paper investigates the Q-factor limits imposed on the far-field detection of the whispering gallery modes of active microspherical resonators. It is shown that the Q-factor measured for a given active microsphere in the far-field using a microscope is significantly lower than that measured using evanescent field collection through a taper. The discrepancy is attributed to the inevitable small asphericity of microspheres that results in mode-splitting which becomes unresolvable in the far-field. Analytic expressions quantifying the Q-factor limits due to small levels of asphericity are subsequently derived. PMID- 26561159 TI - Temperature dependence of lasing characteristics of irregular-shaped microparticle ZnO laser. AB - We investigate the temperature dependence of the lasing characteristics (lasing peak energy spontaneous emission factor beta, and lasing threshold) of an irregular-shaped-ZnO-microparticle laser. The shift of the lasing peak energy with temperature is very small in the range of 120-300 K, thus, indicating that the peak is determined mainly by the resonance energy position of a given cavity mode, and not by the gain spectral peak. On the other hand, beta and lasing threshold are strongly dependent on temperature; beta reaches a maximum at a particular temperature, whereas the lasing threshold exhibits a minimum. In comparison with the theoretical calculations, it is found that beta and lasing threshold are optimum at the temperature at which the spontaneous emission spectral peak is in resonance with the peak of the cavity mode. PMID- 26561160 TI - Tweezers controlled resonator. AB - We experimentally demonstrate trapping a microdroplet by using an optical tweezer and then activating it as a microresonator by bringing it close to a tapered fiber coupler. Our tweezers facilitated the tuning of the coupling from the under coupled to the critically-coupled regime while the quality-factor [Q] is 12 million and the resonator's size is at the 80 MUm scale. PMID- 26561161 TI - Dynamic wave field synthesis: enabling the generation of field distributions with a large space-bandwidth product. AB - We present a novel approach for the design and fabrication of multiplexed computer generated volume holograms (CGVH) which allow for a dynamic synthesis of arbitrary wave field distributions. To achieve this goal, we developed a hybrid system that consists of a CGVH as a static element and an electronically addressed spatial light modulator as the dynamic element. We thereby derived a new model for describing the scattering process within the inhomogeneous dielectric material of the hologram. This model is based on the linearization of the scattering process within the Rytov approximation and incorporates physical constraints that account for voxel based laser-lithography using micro fabrication of the holograms in a nonlinear optical material. In this article we demonstrate that this system basically facilitates a high angular Bragg selectivity on the order of 1 degrees . Additionally, it allows for a qualitatively low cross-talk dynamic synthesis of predefined wave fields with a much larger space-bandwidth product (SBWP >= 8.7 * 10(6)) as compared to the current state of the art in computer generated holography. PMID- 26561162 TI - Thermally tunable polarization by nanoparticle plasmonic resonance in photonic crystal fibers. AB - A photonic crystal fiber selectively filled with silver nanoparticles dispersed in polydimethylsiloxane has been numerically studied via finite elements analysis. These nanoparticles possess a localized surface plasmon resonance in the visible region which depends on the refractive index of the surrounding medium. The refractive index of polydimethylsiloxane can be thermally tuned leading to the design of polarization tunable filters. Filters found with this setup show anisotropic attenuation of the x-polarization fundamental mode around alpha(x) = 1200dB/cm remarkably higher than the y-polarization mode. Moreover, high fiber birefringence and birefringence reversal is observed in the spectral region of the plasmon. PMID- 26561163 TI - Compact multi-projection 3D display system with light-guide projection. AB - We propose a compact multi-projection based multi-view 3D display system using an optical light-guide, and perform an analysis of the characteristics of the image for distortion compensation via an optically equivalent model of the light-guide. The projected image traveling through the light-guide experiences multiple total internal reflections at the interface. As a result, the projection distance in the horizontal direction is effectively reduced to the thickness of the light guide, and the projection part of the multi-projection based multi-view 3D display system is minimized. In addition, we deduce an equivalent model of such a light-guide to simplify the analysis of the image distortion in the light-guide. From the equivalent model, the focus of the image is adjusted, and pre-distorted images for each projection unit are calculated by two-step image rectification in air and the material. The distortion-compensated view images are represented on the exit surface of the light-guide when the light-guide is located in the intended position. Viewing zones are generated by combining the light-guide projection system, a vertical diffuser, and a Fresnel lens. The feasibility of the proposed method is experimentally verified and a ten-view 3D display system with a minimized structure is implemented. PMID- 26561164 TI - Octave-spanning hyperspectral coherent diffractive imaging in the extreme ultraviolet range. AB - Soft x-ray microscopy is a powerful imaging technique that provides sub-micron spatial resolution, as well as chemical specificity using core-level near-edge x ray absorption fine structure (NEXAFS). Near the carbon K-edge (280-300 eV) biological samples exhibit high contrast, and the detailed spectrum contains information about the local chemical environment of the atoms. Most soft x-ray imaging takes place on dedicated beamlines at synchrotron facilities or at x-ray free electron laser facilities. Tabletop femtosecond laser systems are now able to produce coherent radiation at the carbon K-edge and beyond through the process of high harmonic generation (HHG). The broad bandwidth of HHG is seemingly a limitation to imaging, since x-ray optical elements such as Fresnel zone plates require monochromatic sources. Counter-intuitively, the broad bandwidth of HHG sources can be beneficial as it permits chemically-specific hyperspectral imaging. We apply two separate techniques - Fourier transform spectroscopy, and lensless holographic imaging - to obtain images of an object simultaneously at multiple wavelengths using an octave-spanning high harmonic source with photon energies up to 30 eV. We use an interferometric delay reference to correct for nanometer-scale fluctuations between the two HHG sources. PMID- 26561165 TI - Resolution-enhanced integral imaging using two micro-lens arrays with different focal lengths for capturing and display. AB - We proposed a resolution enhanced integral imaging display method using two micro lens arrays (MLA) with different focal lengths for capturing and display respectively. An elemental image array (EIA) is captured with MLA of focal length of f(1) and a processed EIA is displayed with MLA of focal length of f(2) which is larger than f(1). We enlarge the "effective area" in processed EIA to increase the information obtained by viewer, in other words, enhance the viewing resolution. The two micro-lens arrays for capturing and display are g and mg distant from display device respectively, and we can get m(2) times resolution enhancement. PMID- 26561166 TI - High-power, high signal-to-noise ratio single-frequency 1 MUm Brillouin all-fiber laser. AB - We demonstrate a high-power, high signal-to-noise ratio single-frequency Brillouin all-fiber laser with high slope efficiency at 1 MUm wavelength. The laser is pumped by an amplified single-longitudinal-mode distributed Bragg reflector fiber laser with a linewidth of 33 kHz. By optimizing the length of the Brillouin ring cavity to 10 m, stable single-frequency Brillouin fiber laser is obtained with 3 kHz linewidth owing to the linewidth narrowing effect. At the launched pump power of 2.15 W, the Brillouin fiber laser generates maximum output power of 1.4 W with a slope efficiency of 79% and the optical signal-to-noise ratio of 77 dB. PMID- 26561167 TI - Terahertz-field-induced optical birefringence in common window and substrate materials. AB - We apply intense terahertz (THz) electromagnetic pulses with field strengths exceeding 2 MV cm(-1) at ~1 THz to window and substrate materials commonly used in THz spectroscopy and determine the induced optical birefringence. Materials studied are diamond, sapphire, magnesium oxide (MgO), polymethylpentene (TPX), low-density polyethylene (LDPE), silicon nitride membrane (SiN) and crystalline quartz. We observe a Kerr-effect-type transient birefringence in all samples, except in quartz and Si, where, respectively, a linear electrooptic signal and a response beyond the perturbative regime are found. We extract the nonlinear refractive indices and the electrooptic coefficient (in the case of quartz) of these materials and discuss implications for their use as windows or substrates in THz pump-optical probe spectroscopy. PMID- 26561168 TI - Low-voltage high-speed coupling modulation in silicon racetrack ring resonators. AB - We demonstrate a low-voltage high-speed modulator based on a silicon racetrack resonator with a tunable Mach-Zehnder interferometer coupler. Both static measurement and dynamic modulation experiment are carried out. The 3-dB electro optic bandwidth is measured to be >30 GHz beyond the limit by the cavity photon lifetime. A 32 Gb/s on-off keying (OOK) modulation is realized under a peak-to peak drive voltage as low as 0.4 V, and a 28 Gb/s binary phase-shift-keying (BPSK) modulation is realized with a drive voltage of 3 V. The low drive voltages results in low energy consumptions of ~13.3 fJ/bit and ~1.2 pJ/bit for OOK and BPSK modulations, respectively. PMID- 26561169 TI - Radiation-induced photoluminescence enhancement of Bi/Al-codoped silica optical fibers via atomic layer deposition. AB - The radiation-induced photoluminescence (PL) properties of Bi/Al-codoped silica optical fibers were investigated. The Bi/Al-related materials were doped into fiber core via atomic layer deposition. The pristine fiber samples were irradiated with different doses, and its absorption and PL properties were studied. A new absorption peak appeared at approximately 580 nm, and the intensity of absorption peaks is increased with the increasing of radiation doses. When the fiber samples were excited with a 532 nm pump, the intensity of the near infrared fluorescence decreased lightly. However, when the fiber samples were excited with a 980 nm pump the intensity of the fluorescence increased significantly with the increase of radiation doses (0-2.0 kGy). The intensity of fluorescence decreased when the radiation doses were increased up to 3.0 kGy. furthermore, the fluorescence intensity of the 1410 nm band increased much more than that the 1150 nm band. In addition, the microstructural characteristics of the Bi/Al-codoped silica optical fibers were analyzed using electron spin resonance (ESR). Many radiation-induced defect centers were present, and the intensity of the ESR signals also increased with the increase of radiation doses. The photoluminescence properties and microstructural characteristics were related in the radiated Bi-related silica optical fibers. A possible underlying mechanism for the radiation-induced photoluminescence enhancement process in the Bi/Al doped silica fiber is discussed. PMID- 26561170 TI - Investigation on pulse shaping in fiber laser hybrid mode-locked by Sb(2)Te(3) saturable absorber. AB - We report a study on a hybrid mode-locked fiber laser with two saturable absorbers: slow and fast, integrated in a single device. Amorphous antimony telluride (Sb(2)Te(3)) layer was deposited on side-polished fiber to form the slow saturable absorber due to the third order nonlinear susceptibility of Sb(2)Te(3). Additionally, an unsymmetrical design of the device causes polarization-dependent losses and together with polarization controller allows to use a nonlinear polarization evolution to form the artificial fast saturable absorber. Sub-200 fs soliton pulses with 0.27 nJ of pulse energy were generated in the hybrid mode-locked Er-doped fiber laser. Differences in the dynamics of mode-locked laser are further investigated with the use of slow and fast saturable absorbers solely, and compared with the hybrid device. Joint operation of two saturable absorbers enhances the laser performance and stability. The conducted experiments allowed to define roles of each mechanism on the pulse shaping in the laser cavity. PMID- 26561171 TI - High-modulation efficiency operation of GaInAsP/InP membrane distributed feedback laser on Si substrate. AB - The direct modulation characteristics of a membrane distributed feedback (DFB) laser on a silicon substrate were investigated. Enhancement of the optical confinement factor in the membrane structure facilitates the fabrication of a strongly index-coupled (kappa(I) = 1500 cm(-1)) DFB laser with the cavity length of 80 um and a threshold current of 270 uA. Small-signal modulation measurements yielded a -3dB bandwidth of 9.5 GHz at 1.03-mA bias current, with modulation efficiency of 9.9 GHz/mA(1/2), which is, to the best of our knowledge, the highest value among those reported for DFB lasers. PMID- 26561172 TI - Damage threshold of platinum/carbon multilayers under hard X-ray free-electron laser irradiation. AB - We evaluated the irradiation damage induced by hard X-ray free-electron lasers to platinum/carbon multilayers intended for use in a focusing reflective mirror. In order to determine the damage threshold, we compared X-ray reflectivities before and after irradiation at the first-order Bragg angle using a focused X-ray free electron laser with a beam size of approximately 1 MUm and a pulse energy ranging from 0.01 to 10 MUJ at a photon energy of 10 keV. We confirmed that the damage threshold of the platinum/carbon multilayer with a bilayer period of 3 nm was 0.051 MUJ/MUm(2), which is sufficiently higher than that in practical applications. PMID- 26561173 TI - Distributed OTDR-interferometric sensing network with identical ultra-weak fiber Bragg gratings. AB - We demonstrate a distributed sensing network with 500 identical ultra-weak fiber Bragg gratings (uwFBGs) in an equal separation of 2m using balanced Michelson interferometer of the phase sensitive optical time domain reflectometry (phi OTDR) for acoustic measurement. Phase, amplitude, frequency response and location information can be directly obtained at the same time by using the passive 3 * 3 coupler demodulation. Lab experiments on detecting sound waves in water tank are carried out. The results show that this system can well demodulate distributed acoustic signal with the pressure detection limit of 0.122Pa and achieve an acoustic phase sensitivity of around -158dB (re rad/MUPa) with a relatively flat frequency response between 450Hz to 600Hz. PMID- 26561174 TI - Subaperture stitching test of large steep convex spheres. AB - Limited by the aperture and f/number of the transmission sphere (TS), large convex spheres with very small R/number (ratio of the radius of curvature to the aperture) cannot be tested in a single measurement with a standard interferometer. We present the algorithm and troubleshooting for subaperture stitching test of a half meter-class convex sphere with R/0.61. Totally 90 off axis subapertures are arranged on 5 rings around the central one. Since the subaperture is so small, its surface error is comparable with that of the TS reference error. Hence a self-calibrated stitching algorithm is proposed to separate the reference error from the measurements. Another serious problem is the nonlinear mapping between the subaperture's local coordinates and the full aperture's global coordinates. The nonlinearity increases remarkably with the off axis angle. As a result, we cannot directly remove power from the full aperture error map as we usually do. Otherwise incorrect spherical aberration will be generated. We therefore propose the sphericity assessment algorithm to match the stitched surface error with a best-fit sphere. The residual is true surface error which can be used for corrective figuring or for tolerance assessment. The self calibrated stitching and troubleshooting are demonstrated experimentally. PMID- 26561175 TI - Wavelength-tunable Yb-doped passively Q-switching fiber laser based on WS(2) saturable absorber. AB - We have fabricated an Yb-doped passively Q-switching fiber laser based on WS(2) saturable absorber. Both the operating wavelength and the repetition rate can be tuned in a wide range. The operating wavelength can be continuously tuned from 1027 nm to 1065 nm under the Q-switching state at a fixed pump power, while the repetition rate increases from 60.2 kHz to 97.0 kHz by varying pump power at a fixed wavelength of 1048.1 nm. The shortest pulse duration of 1.58 us was observed. To the best of our knowledge, it's the first demonstration of WS(2) based passively Q-switching fiber laser with a wide tunable range at 1.0 MUm band. PMID- 26561176 TI - Power fading mitigation of 40-Gbit/s 256-QAM OFDM carried by colorless laser diode under injection-locking. AB - The pre-compensation on power fading effect of a colorless laser diode (CLD) carried 40-Gbit/s 256-QAM OFDM transmission during 25-km is demonstrated. By offsetting the DC bias to thrice the threshold (I(th)) and increasing the injection to 0 dBm, the CLD not only enhances its coherence but also suppresses modulation throughput declination and reduces the relative intensity related noise floor to -50 dBm. Modeling the receiving power of the delivered 256-QAM OFDM subcarriers is established, indicating that raising the bias to 3I(th) down shifts the power fading induced notch to 8.8 GHz. This further degrades the OFDM subcarrier peak power by -2.9 dB after 25-km transmission, and the corresponded signal-to-noise ratio (SNR), error vector magnitude (EVM) and bit-error-rate (BER) are 26.1 dB, 4.9% and 6.5 * 10(-3), respectively. Pre-leveling the OFDM subcarrier as well as the modulation throughput effectively compromises the over bias enlarged power fading to promote transmission. With a pre-leveled power slope of 1.5 dB/GHz for 256-QAM OFDM data, the modulation throughput declination of the high biased CLD significantly mitigates under BtB transmission, enabling the receiving sensitivity at -7.2 dBm with SNR, EVM and BER of 29.9 dB, 3.1% and 1.5 * 10(-4), respectively. Increasing the pre-leveling slope to 3.2 dB/GHz minimizes the fiber dispersion induced power fading, which improves the receiving SNR, EVM and BER to 27.4 dB, 4.2% and 2.6 * 10(-3), respectively, with receiving sensitivity of -3 dBm and power penalty of 4.2 dB after 25-km SMF transmission. PMID- 26561177 TI - Optical properties of strain-compensated CdSe/ZnSe/(Zn,Mg)Se quantum well microdisks. AB - Strain-compensated CdSe/ZnSe/(Zn,Mg)Se quantum well structures that were grown on (In,Ga)As allow for efficient room-temperature photoluminescence and spectral tuning over the whole visible range. We fabricated microdisk cavities from these samples by making use of a challenging chemical structuring technique for selective and homogeneous removal of the (In,Ga)As sacrificial layer below the quantum structure. The observed whispering gallery modes in our microdisks are mainly visible up to photon energies of ~ 2.3 eV due to strong self-absorption. As extinction coefficients and effective refractive indices are dominated by the quantum well material CdSe, thick quantum wells (> 3 monolayer) are necessary to observe resonances in the corresponding quantum well emission. PMID- 26561178 TI - Decoupling and tuning the light absorption and scattering resonances in metallic composite nanostructures. AB - Utilizing the localized surface plasmon resonance (LSPR) effect of metallic nanoparticles enables their usage as contrast agents in a variety of applications for medical diagnostics and treatment. Those applications can use both the very strong absorption and scattering properties of the metallic nanoparticle due to their LSPR effects. There are certain applications where domination of the scattering over absorption or vice versa would be an advantage. However, the scattering and absorption resonance peaks have practically the same spectral location for solid noble metal nanoparticles at a certain domination of one over the other. In this paper we present gold nanoparticles coated with silicon that switches the order between the scattering and the absorption magnitude at the resonance peak by up to 34% in scattering-absorption ratio and tune the plasmon resonance over the spectrum by up to 56nm. This is obtained by modifying the refractive index of the silicon coating of the nanoparticle by illuminating it with a pumping light due to the plasma dispersion effect in silicon. PMID- 26561179 TI - Comparison of microfacet BRDF model to modified Beckmann-Kirchhoff BRDF model for rough and smooth surfaces. AB - A popular class of BRDF models is the microfacet models, where geometric optics is assumed. In contrast, more complex physical optics models may more accurately predict the BRDF, but the calculation is more resource intensive. These seemingly disparate approaches are compared in detail for the rough and smooth surface approximations of the modified Beckmann-Kirchhoff BRDF model, assuming Gaussian surface statistics. An approximation relating standard Fresnel reflection with the semi-rough surface polarization term, Q, is presented for unpolarized light. For rough surfaces, the angular dependence of direction cosine space is shown to be identical to the angular dependence in the microfacet distribution function. For polished surfaces, the same comparison shows a breakdown in the microfacet models. Similarities and differences between microfacet BRDF models and the modified Beckmann-Kirchhoff model are identified. The rationale for the original Beckmann-Kirchhoff F(bk)(2) geometric term relative to both microfacet models and generalized Harvey-Shack model is presented. A modification to the geometric F(bk)(2) term in original Beckmann-Kirchhoff BRDF theory is proposed. PMID- 26561180 TI - Enhancement of spectrum strength in holographic sensing in nanozeolites dispersed acrylamide photopolymer. AB - Holographic sensing of organic vapor is characterized at transmission and reflection geometries in ZSM-5 nanozeolites dispersed acrylamide photopolymer. Nano-zeolites as absorption medium are dispersed into the polymer to enhance the absorptivity to organic vapor. Obvious enhancements of spectrum strength are observed during the sensing process. Two primary factors causing the enhancement, absorption of nanozeolites and photopolymerization induced by broadband white light, are analyzed experimentally. Significant increment provides a quick and intuitive identification strategy for holographic sensing. Accompanying with the wavelength blue-shift, the shrinkage of sample is measured quantitatively under homogeneous white light. It is further demonstrated that the significance of nanozeolites absorption. Finally a theoretical model with mutual diffusion is used to simulate the swelling process. This study provides significant foundation for the application of holographic sensor. PMID- 26561181 TI - Effects of Raman pump power distribution on output spectrum in a multi-wavelength BRFL: publisher's note. AB - This publisher's note amends the author list and Acknowledgments of a recent publication [Opt. Express23, 25570 (2015)]. PMID- 26561182 TI - Broadband, wide-angle, low-scattering terahertz wave by a flexible 2-bit coding metasurface. AB - Expanding bandwidths and arbitrary control of technology remain key issues in the field of electromagnetic waves, especially in terahertz (THz) wave. In this paper, we propose a novel method to achieve broadband low-scattering THz characteristics with wide-angle and polarization independence by a 2-bit flexible and nonabsorptive coding metasurface. The coding metasurface is composed of four digital elements based on double cross metallic line for "00", "01", "10", and "11." The reflection phase difference of neighboring elements is about 90 degrees over a broad THz frequency band and wide incident angles. The low scattering coefficients below -10 dB were achieved over a wide frequency band from 0.8 THz to 1.5 THz when the incident angle is less than 50 degrees by coding the four elements sequences. This superior property is maintained when the flexible coding metasurface is wrapped around a metallic cylinder with different dimensions. These results present a novel method to control THz waves freely and demonstrate significant scientific value in practical applications. PMID- 26561183 TI - Toroidal dipolar response by a dielectric microtube metamaterial in the terahertz regime. AB - Due to metal losses in plasmonic metamaterials, high-refractive-index dielectrics are promising to improve optical performances of their metallic counterparts. In this paper, a LiTaO(3) microtube metamaterial is numerically investigated to explore the toroidal dipolar resonance based on the multipole expansion theory. The local field strength probed on the central axis of the microtube is greatly enhanced for the toroidal dipolar mode, forming a strong hot spot concentrated in the deep-subwavelength scale. Furthermore, we also show the influences of geometrical parameter on the quality (Q) factor of the toroidal mode. The high Q factor and strongly concentrated field strength in the toroidal microtube metamaterial offer application potentials such as sensing, energy havesting, particle trapping, and nonlinear optical effects. PMID- 26561184 TI - Adjusting diffraction spectrum of an echelon-like grating influenced by surface plasmon of nanomaterials. AB - This article aims to study the varying diffraction spectrum phenomenon influenced by surface plasmon of nanomaterials. Experiments used silver nanoparticles to build the echelon-like grating as test samples, where the grating spacing of line pattern is 10 MUm and within the width of silver nanoparticles line is 5 MUm alternately. In this work, the silver stripes with gradient thickness were first formed line pattern alternately with glancing angle deposition and photolithography, and then annealed at temperature of 250 degrees C for 3 mins to fabricate the silver nanoparticles as bowl-like forms. Thicknesses of the silver nanoparticles in the echelon-like grating increase from 0 nm to 40 nm and their diameters grow from 0 nm to 35 nm with quasilinear increment simultaneously. Analyzing the varying diffraction spectrum was focused on observing the first order diffraction by changing the beam size and the probe position of the incident light. The significant results show that the bigger the incident light beam size, the larger the peak wavelength difference (Deltalambda) of the two first order diffractions. Moreover, the peak spectrum is shifted to long wavelength and Deltalambda is diminished by probing area with big size of nanoparticles. PMID- 26561185 TI - Light-field moment microscopy with noise reduction. AB - We experimentally demonstrate a light-field moment microscopy (LFMM). The proposed technique employs a better estimation of the intensity derivative in solving the Poisson equation and therefore can significantly reduce the noise and error in the reconstructed light-field moment. The light field can be reconstructed then by using the moment, enabling the perspective view and depth estimation of the object. The proposed LFMM can be simply implemented using a standard commercial light microscope. This will open up new possibility for standard microscopes in high-resolution light-field observations. PMID- 26561186 TI - Stochastic interference in a dispersive fiber excited by a partially coherent source. AB - We have investigated the stochastic interference of two temporally separated pulses in optical fiber due to chromatic dispersion of the fiber and partial coherence of the source. An analytical expression for the correlation function that describes the stochastic interference is derived. The results show that the correlation function becomes negligibly small as the temporal coherence of the source becomes very small and chromatic dispersion becomes very large and in this case, the total mean power is simply the sum of the power of individual pulses. Finally, the theory is extended to include the case of arbitrary number of temporally separated pulses. PMID- 26561187 TI - 80 Gbit/s, 256 QAM coherent transmission over 150 km with an injection-locked homodyne receiver. AB - We demonstrate an 80 Gbit/s, 5 Gsymbol/s 256 QAM coherent optical transmission by employing an injection-locked homodyne detection circuit based on both fiber lasers and LDs. With either circuit, low phase noise carrier-phase synchronization between the transmitted data signal and an LO were achieved with a phase noise variance of only 0.2 degrees. As a result, we have successfully transmitted an 80 Gbit/s data signal over 150 km with a simple receiver configuration. This is the highest QAM multiplicity yet realized with injection locked homodyne detection. PMID- 26561188 TI - Diffractive optical element with asymmetric microrelief for creating visual security features. AB - We demonstrate a new security feature for visual control of the authenticity of optical security features - the change of the images when the optical element is turned by 180 degrees ("switch-180 degrees "). The diffractive optical element has an asymmetric microrelief structure resulting from the asymmetry of the scattering pattern. The phase function of the diffractive optical element is computed in terms of Fresnel's scalar wave model. We developed efficient algorithms for computing the structure of flat optical elements to produce the switch effect. A sample of flat optical element for the "switch-180" effect has been developed using electron-beam lithography. The effectiveness of the development is illustrated by the photos and the video captured from a real sample. The visual "switch-180 degrees " effect is easy to control allowing secure anti-counterfeit protection of the optical security feature developed. The new security feature is already used to protect IDs and excise stamps. PMID- 26561189 TI - Analysis of the laser oxidation kinetics process of In-In(2)O(3) MTMO photomasks by laser direct writing. AB - One kind of novel grayscale photomask based on Metal-transparent-metallic-oxides (MTMOs) system fabricated by laser direct writing was demonstrated recently. Here, a multilayer oxidation model of In-In(2)O(3) film with a glass substrate was proposed to study the pulsed laser-induced oxidation mechanism. The distribution of the electromagnetic field in the film is calculated by the transfer matrix method. Temperature fields of the model are simulated based on the heat transfer equations with the Finite-Difference Time-Domain method. The oxidation kinetics process is studied based on the laser-induced Cabrera-Mott theory. The simulated oxidation processes are consistent with the experimental results, which mean that our laser-induced oxidation model can successfully interpret the fabrication mechanism of MTMO grayscale photomasks. PMID- 26561190 TI - Giantically blue-shifted visible light in femtosecond mid-IR filament in fluorides. AB - A giant blue shift (more than 3000 nm) of an isolated visible band of supercontinuum was discovered and studied in the single filament regime of Mid-IR femtosecond laser pulse at powers slightly exceeding critical power for self focusing in fluorides. At the pulse central wavelength increasing from 3000 nm to 3800 nm the spectral maximum of the visible band is shifted from 570 nm and 520 nm up to 400 nm and 330 nm for BaF(2) and CaF(2), respectively, its spectral width (FWHM) being reduced from 50 - 70 nm to 14 nm. It is shown that the formation of this narrow visible wing is a result of the interference of the supercontinuum components in the anomalous group velocity dispersion regime. PMID- 26561191 TI - Channel waveguides and y-junctions in x-cut single-crystal lithium niobate thin film. AB - Proton exchanged channel waveguides in x-cut single-crystal lithium niobate thin film could avoid optical leakage loss which existed in the z-cut case. Indicated by simulations, the mechanism and condition of the optical leakage loss were studied. The light energy in the exchanged layer and the mode sizes were calculated to optimize the parameters for fabrication. By a very short time (3 minutes) proton exchange process without anneal, the channel waveguide with 2 MUm width and 0.16 MUm exchanged depth in the x-cut lithium niobate thin film had a propagation loss as low as 0.2 dB/cm at 1.55 MUm. Furthermore, the Y-junctions based on the low-loss waveguide were designed and fabricated. For a Y-junction based on the 3 MUm wide channel waveguide with 8000 MUm bending radius, the total transmission could reach 85% ~90% and the splitting ratio maintained at a stable level around 1:1. The total length was smaller than 1 mm, much shorter than the conventional Ti-diffused and proton exchanged Y-junctions in bulk lithium niobate. PMID- 26561192 TI - Terahertz metasurfaces with a high refractive index enhanced by the strong nearest neighbor coupling. AB - The realization of high refractive index is of significant interest in optical imaging with enhanced resolution. Strongly coupled subwavelength resonators were proposed and demonstrated at both optical and terahertz frequencies to enhance the refractive index due to large induced dipole moment in meta-atoms. Here, we report an alternative design for flexible free-standing terahertz metasurface in the strong coupling regime where we experimentally achieve a peak refractive index value of 14.36. We also investigate the impact of the nearest neighbor coupling in the form of frequency tuning and enhancement of the peak refractive index. We provide an analytical circuit model to explain the impact of geometrical parameters and coupling on the effective refractive index of the metasurface. The proposed meta-atom structure enables tailoring of the peak refractive index based on nearest neighbor coupling and this property offers tremendous design flexibility for transformation optics and other index-gradient devices at terahertz frequencies. PMID- 26561193 TI - Three-photon-induced blue emission with narrow bandwidth from hot flower-like ZnO nanorods. AB - ZnO nanorods (NRs) self-organized into flowers were synthesized at different temperatures ranging from 100 degrees C to 180 degrees C by using the hydrothermal method. The existence of Zn interstitials (Zn(i)) was confirmed by X ray photoelectron spectroscopy and a larger amount of Zn(i) was found in the ZnO NRs prepared at higher temperatures. A redshift of the emission peak of more than 15 nm was observed for the ZnO NRs under single photon excitation. The nonlinear optical properties of the flower-like ZnO NRs were characterized by using focused femtosecond laser light and strong three-photon-induced luminescence was observed at an excitation wavelength of ~750 nm. More interestingly, a large redshift of the emission peak was observed with increasing excitation intensity, resulting in efficient blue emission with a narrow bandwidth of ~30 nm. It was confirmed that the large redshift originates from the heating of the ZnO NRs to a temperature of more than 800 degrees C and the closely packed ZnO NRs in the flowers play a crucial role in heat accumulation. The stable and efficient three-photon-induced blue emission from such ZnO NRs may find potential applications in the fields of optical display, high-temperature sensors and light therapy of tumors. PMID- 26561194 TI - Dynamic frequency-noise spectrum measurement for a frequency-swept DFB laser with short-delayed self-heterodyne method. AB - We proposed and experimentally demonstrated a short-delayed self-heterodyne method with 15.5m delay to get a large-frequency-range laser frequency-noise spectrum over 10Hz to 50 MHz, and an averaging approach to extract the intrinsic frequency noise of a frequency-swept laser. With these two techniques, dynamic frequency-noise spectrum of a frequency-swept DFB laser when free running and servo-controlled are both measured. This measurement method permits accurate and insightful investigation of laser stability. PMID- 26561195 TI - Non-contact sub-nanometer optical repositioning using femtosecond lasers. AB - Optical components like resonator or waveguides often have stringent requirements in term of positioning accuracy during packaging. While this can be done routinely in a laboratory environment, permanently positioning and aligning optical elements with nanometer accuracy in a fully packaged device is a challenging endeavor. Here, we demonstrate the use of femtosecond laser-induced modifications in glass for the remote permanent fine-positioning of an optical element with sub-nanometer resolution. PMID- 26561196 TI - Demodulation of diaphragm based acoustic sensor using Sagnac interferometer with stable phase bias. AB - A stable phase demodulation system for diaphragm-based acoustic sensors is reported. The system is based on a modified fiber-optic Sagnac interferometer with a stable quadrature phase bias, which is independent of the parameters of the sensor head. The phase bias is achieved passively by introducing a nonreciprocal frequency shift between the counter-propagating waves, avoiding the use of complicated active servo-control. A 100 nm-thick graphite diaphragm-based acoustic sensor interrogated by the proposed demodulation system demonstrated a minimum detectable pressure level of ~450 uPa/Hz(1/2) and an output signal stability of less than 0.35 dB over an 8-hour period. The system may be useful as a universal phase demodulation unit for diaphragm-based acoustic sensors as well as other sensors operating in a reflection mode. PMID- 26561197 TI - Determination of 3D molecular orientation by concurrent polarization analysis of multiple Raman modes in broadband CARS spectroscopy. AB - A theoretical description is presented about a new analysis method to determine three-dimensional (3D) molecular orientation by concurrently analyzing multiple Raman polarization profiles. Conventional approaches to polarization Raman spectroscopy are based on single peaks, and their 2D-projected polarization profiles are limited in providing 3D orientational information. Our new method analyzes multiple Raman profiles acquired by a single polarization scanning measurement of broadband coherent anti-Stokes Raman scattering (BCARS). Because the analysis uses only dimensionless quantities, such as intensity ratios and phase difference between multiple profiles, the results are not affected by sample concentration and the system response function. We describe how to determine the 3D molecular orientation with the dimensionless observables by using two simplified model cases. In addition, we discuss the effect of orientational broadening on the polarization profiles in the two model cases. We find that in the presence of broadening we can still determine the mean 3D orientation angles and, furthermore, the degree of orientational broadening. PMID- 26561198 TI - 2-Indolinone a versatile scaffold for treatment of cancer: a patent review (2008 2014). AB - INTRODUCTION: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block. AREAS COVERED: The present review gives an account of the recent patent literature (2008-2014) describing the discovery of 2-indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2 indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-indolinone derivatives for the treatment of cancer reported in international patents have been discussed. EXPERT OPINION: 2-Indolinone is the scaffold of the compounds considered from a medicinal chemistry perspective. Many of them have been developed and marketed for therapeutic use. In cancer chemotherapy, progress has been made in designing selective 2-indolinone derivatives. Some of them show preclinical efficacy. However, 2-indolinone has not exhausted all of its potential in the development of new compounds for clinical applications and remains a great tool for future research. PMID- 26561199 TI - Recombination patterns reveal information about centromere location on linkage maps. AB - Linkage mapping is often used to identify genes associated with phenotypic traits and for aiding genome assemblies. Still, many emerging maps do not locate centromeres - an essential component of the genomic landscape. Here, we demonstrate that for genomes with strong chiasma interference, approximate centromere placement is possible by phasing the same data used to generate linkage maps. Assuming one obligate crossover per chromosome arm, information about centromere location can be revealed by tracking the accumulated recombination frequency along linkage groups, similar to half-tetrad analyses. We validate the method on a linkage map for sockeye salmon (Oncorhynchus nerka) with known centromeric regions. Further tests suggest that the method will work well in other salmonids and other eukaryotes. However, the method performed weakly when applied to a male linkage map (rainbow trout; O. mykiss) characterized by low and unevenly distributed recombination - a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations, our method should work well for high density maps in species with strong recombination interference and will enrich many existing and future mapping resources. PMID- 26561200 TI - HydroCrowd: a citizen science snapshot to assess the spatial control of nitrogen solutes in surface waters. AB - We organized a crowdsourcing experiment in the form of a snapshot sampling campaign to assess the spatial distribution of nitrogen solutes, namely, nitrate, ammonium and dissolved organic nitrogen (DON), in German surface waters. In particular, we investigated (i) whether crowdsourcing is a reasonable sampling method in hydrology and (ii) what the effects of population density, soil humus content and arable land were on actual nitrogen solute concentrations and surface water quality. The statistical analyses revealed a significant correlation between nitrate and arable land (0.46), as well as soil humus content (0.37) but a weak correlation with population density (0.12). DON correlations were weak but significant with humus content (0.14) and arable land (0.13). The mean contribution of DON to total dissolved nitrogen was 22%. Samples were classified as water quality class II or above, following the European Water Framework Directive for nitrate and ammonium (53% and 82%, respectively). Crowdsourcing turned out to be a useful method to assess the spatial distribution of stream solutes, as considerable amounts of samples were collected with comparatively little effort. PMID- 26561201 TI - Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC. AB - Autophagy is considered as a double-edged sword. It can prolong the survival of cancer cells and enhance its resistance to apoptosis, and paradoxically, defective autophagy has been linked to increased tumorigenesis, but the mechanism behind this phenomenon is unclear. In this study, we demonstrated that decreased phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) was correlated with increased autophagy through the Akt/mTOR and Erk signaling pathways in human head and neck squamous cell carcinoma (HNSCC). We also showed that blockage of STAT3 by NSC74859 could markedly induce apoptotic cell death and autophagy. Meanwhile, increased autophagy inhibited apoptosis. The pharmacological or genetic inhibition of autophagy and STAT3 further sensitized HNSCC cells to apoptosis. Furthermore, evidence from xenograft model proved that suppressed STAT3 activity combined with inhibition of autophagy promoted tumor regression better than either treatment alone. Taken together, this present study demonstrated that autophagy alleviates apoptotic cell death in HNSCC, and combination of inhibition of STAT3 by NSC74859 and autophagy might be a promising new therapeutic strategy for HNSCC. PMID- 26561202 TI - Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. AB - Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of BV on the colon cancer and their action mechanisms have not been reported yet. We used cell viability assay and soft agar colony formation assay for testing cell viability, electro mobility shift assay for detecting DNA binding activity of nuclear factor kappa B (NF-kappaB) and Western blotting assay for detection of apoptosis regulatory proteins. We found that BV inhibited growth of colon cancer cells through induction of apoptosis. We also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0-5 MUg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-kappaB) was also inhibited by BV treatment. Besides, we found that BV blocked NF-kappaB activation by directly binding to NF kappaB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF kappaB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibiton. In addition, BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-kappaB. PMID- 26561203 TI - Single-Molecule Localization Microscopy allows for the analysis of cancer metastasis-specific miRNA distribution on the nanoscale. AB - We describe a novel approach for the detection of small non-coding RNAs in single cells by Single-Molecule Localization Microscopy (SMLM). We used a modified SMLM setup and applied this instrument in a first proof-of-principle concept to human cancer cell lines. Our method is able to visualize single microRNA (miR) molecules in fixed cells with a localization accuracy of 10-15 nm, and is able to quantify and analyse clustering and localization in particular subcellular sites, including exosomes. We compared the metastasis-site derived (SW620) and primary site derived (SW480) human colorectal cancer (CRC) cell lines, and (as a proof of principle) evaluated the metastasis relevant miR-31 as a first example. We observed that the subcellular distribution of miR-31 molecules in both cell lines was very heterogeneous with the largest subpopulation of optically acquired weakly metastatic cells characterized by a low number of miR-31 molecules, as opposed to a significantly higher number in the majority of the highly metastatic cells. Furthermore, the highly metastatic cells had significantly more miR-31 molecules in the extracellular space, which were visualized to co-localize with exosomes in significantly higher numbers. From this study, we conclude that miRs are not only aberrantly expressed and regulated, but also differentially compartmentalized in cells with different metastatic potential. Taken together, this novel approach, by providing single molecule images of miRNAs in cellulo can be used as a powerful supplementary tool in the analysis of miRNA function and behaviour and has far reaching potential in defining metastasis-critical subpopulations within a given heterogeneous cancer cell population. PMID- 26561204 TI - Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway. AB - The Hippo signaling pathway plays a crucial role in regulating tissue homeostasis, organ size, tumorigenesis and cancer chemoresistance when deregulated. Physiologically, the Hippo core kinase cassette that consists of mamma-lian STE20-like protein kinase 1/2 (MST1/2), and large tumour suppressor 1/2 (LATS1/2), together with the adaptor proteins Salvador homologue 1 (SAV1) and MOB kinase activator 1 (MOB1), tightly restricts the activities of homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) to low levels. However, how the Hippo kinase cassette core components are simultaneously inhibited, to exhibit constitutively inactivated Hippo signaling and activated YAP/TAZ in cancer remains puzzling. Herein, we reported that miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-181c in the progression of pancreatic cancer, but also may represent a new therapeutic target and prognostic marker. PMID- 26561206 TI - In situ determination of the depuration of three- and four-ringed polycyclic aromatic hydrocarbons co-adsorbed onto mangrove leaf surfaces. AB - A dual-wavelength fiber-optic fluorimetry for the in situ simultaneous determinations of fluorene (Flu), phenanthrene (Phe) and pyrene (Pyr) adsorbed onto the leaf surfaces of living Avicennia marina (Am) seedling were developed and used to study the depuration kinetics of the three PAHs, adsorbed individually or mixed together, onto living Am leaf surfaces. Limits of detection for the in situ measurements of adsorbed Flu, Phe and Pyr were 4.62, 2.75 and 1.38 ng spot(-1), respectively. The depuration kinetics of the three selected polycyclic aromatic hydrocarbons (PAHs) are divided into rapid and slow phases; both phases followed the same first-order kinetics with relative clearance rates of Flu > Phe > Pyr during the rapid phase, and a clearance rate order of Pyr > Flu > Phe during the slow phase. For the three PAHs co-adsorbed on living Am leaf surfaces, a significant synergistic effect was detected during the rapid phase clearance; conversely, an antagonistic effect was observed during the slow phase. However, the synergistic effect dominated during both phases of the depuration process, and the co-adsorption of PAHs promoted the clearance of all three compounds from the mangrove leaf surfaces. These findings demonstrate a novel analytical method for in situ characterization of multiple PAHs adsorbed onto the plant surfaces. PMID- 26561205 TI - MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma. AB - Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis. PMID- 26561207 TI - Quality of life in adolescents and young adults with CHD is not reduced: a systematic review and meta-analysis. AB - PURPOSE: We performed a systematic review and meta-analysis of observational studies assessing quality of life in adolescents and young adults born with CHD compared with age-matched controls. METHODS: We carried out a systematic search of the literature published in Medline, Embase, PsychINFO, and the Cochrane Library's Database (1990-2013); two authors independently extracted data from the included studies. We used the Newcastle-Ottawa scale for quality assessment of studies. A random effects meta-analysis model was used. Heterogeneity was assessed using the I2-test. RESULTS: We included 18 studies with 1786 patients. The studies were of acceptable-to-good quality. The meta-analysis of six studies on quality of life showed no significant difference - mean difference: -1.31; 95% confidence intervals: -6.51 to +3.89, I2=90.9% - between adolescents and young adults with CHD and controls. Similar results were found in 10 studies not eligible for the meta-analysis. In subdomains, it seems that patients had reduced physical quality of life; however, social functioning was comparable or better compared with controls. CONCLUSION: For the first time in a meta-analysis, we have shown that quality of life in adolescents and young adults with CHD is not reduced when compared with age-matched controls. PMID- 26561208 TI - Dehydrochlorination of Hexachlorocyclohexanes Catalyzed by the LinA Dehydrohalogenase. A QM/MM Study. AB - The elucidation of the catalytic role of LinA dehydrohalogenase in the degradation processes of hexachlorocyclohexane (HCH) isomers is extremely important to further studies on the bioremediation of HCH polluted areas. Herein, QM/MM free energy simulations are employed to provide the details of the dehydrochlorination reaction of two HCH isomers (gamma and beta). In particular, the role of the protonation state of one of the catalytic residues-His73-is explored. Based on our calculations, two distinct minimum free energy pathways (concerted and stepwise) were found for gamma-HCH and beta-HCH. The choice of the reaction channel for the dehydrochlorination reactions of gamma- and beta-HCH was shown to depend on the initial mutual orientations of the reacting species in the active site and the protonation form of His73. The sequential pathway comprises the transfer of the proton (Hdelta1) between His73 and Asp25 and subsequently the H1/Cl2 pair elimination from the substrate molecule. Within a concerted mechanism, the dehydrochlorination reaction of gamma-/beta-HCH is initiated with neutral His73 and the Hdelta1 proton is transferred upon final product formation. We found that the concerted pathway for beta-HCH results in significantly higher free energy of activation than the stepwise route and therefore can be disregarded as not a feasible mechanism. On the other hand, the reaction that occurs with much lower energetic barrier requires a stronger base (i.e., anionic His73) to abstract the proton (H1) from the substrate molecule. The presence of such transient form of His results in higher energy than the respective Michaelis complex and was observed only in the stepwise pathway for both isomers. Furthermore, we have concluded that both pathways (concerted and stepwise) are feasible for the dehydrochlorination reaction of gamma-HCH. The activation free energies obtained from the M05-2X/6-31+G(d,p) corrected path coordinate PMF profiles for the dehydrochlorination reactions of the gamma-/beta-HCH are in good agreement with the experimental values. PMID- 26561209 TI - Regorafenib with a fluoropyrimidine for metastatic colorectal cancer after progression on multiple 5-FU-containing combination therapies and regorafenib monotherapy. AB - We present 2 patients with metastatic colorectal cancer who had progressed despite treatment with first-line FOLFOX and second-line FOLFIRI combination chemotherapy regimens. After failing these fluoropyrimidine-based regimens, both patients received additional cytotoxic and targeted therapies with eventual disease progression. These therapies included capecitabine plus dabrafenib and trametinib, regorafenib monotherapy, and regorafenib with panitumumab. After exhausting available options, both patients were offered regorafenib with either 5-fluorouracil (5-FU) or capecitabine. These therapies are individually approved for the treatment of colorectal cancer but have not yet been studied in combination. This regimen produced stable disease in both patients with acceptable toxicity. One patient continued therapy for 17 months. Although these patients previously progressed during treatment with regorafenib, capecitabine or 5-FU, the combination had some activity in both cases of refractory metastatic colorectal cancer and may be considered in the palliative setting. In bedside-to bench cell culture experiments performed after the clinical observations, we observed sensitivity of human colorectal cancer cell lines (N = 4) to single agent regorafenib or 5-FU and evidence of synergy with the combination therapy. Synergistic effects were noted in colorectal cancer cells with KRAS mutation, BRAF mutation, and p53 mutation, as well as mismatch repair deficient cells. Regorafenib suppressed Mcl-1 and Bcl-XL in treated cancer cells that may have contributed to the anticancer efficacy including in combination with 5-FU. The safety and efficacy of regorafenib with 5-FU or capecitabine in combination should be further investigated as a therapy for patients with refractory metastatic colorectal cancer, including individuals who had progressed on regorafenib monotherapy. PMID- 26561210 TI - WNT receptors profile expression in mature blood cells and immature leukemic cells: RYK emerges as a hallmark receptor of acute leukemia. AB - BACKGROUND: Wnt signaling induces a plethora of intracellular responses that dictate normal or abnormal cellular behavior. Abnormal WNT signaling has been related to the development of leukemogenic processes. In this regard, it is important to know the expression profile of WNT receptors in normal and malignant cells, in order to understand the WNT mechanisms that control the cell behavior. This work aimed to determine the WNT receptors expression profile in normal and leukemia cells. METHODS: Expression of WNT receptors was determined by flow cytometry using leukemia-derived cell lines, peripheral blood cells, and blood marrow samples from healthy volunteers and acute leukemia patients. RESULTS: Despite the heterogenic WNT receptors expression in mature normal blood cells and in immature tumorigenic cells, the RYK receptor was found highly express in leukemia cells, but not in normal cells. RYK expression was found mainly in cells positive to immature markers like CD33, CD13, CD7, and CD117. CONCLUSIONS: Our data show differences in FZD receptors expression between T and B leukemic cells, but both cell types and also myeloblast-derived cells express high levels of RYK. The association of RYK expression with immature markers indicates its possible use as a diagnostic marker or therapeutic target. PMID- 26561211 TI - Evaluation of Results of Diagnostic Ureteroscopy in Chronic Hemodialysis Patients. AB - OBJECTIVES: To investigate the safety of diagnostic ureteroscopy (dURS) in chronic hemodialysis patients. METHODS: The data of chronic hemodialysis patients (group I) and the patients with normal estimated glomerular filtration rate (eGFR) (group II) who had dURS between 2004 and 2014 were analyzed retrospectively. eGFR, complications, and postoperative stent placement were noted in all patients. Continuous and categorical variables were compared between the groups. p < 0.05 was considered as statistically significant. RESULTS: Overall complication rate of group I was 10.5%, while this rate was 4.8% in group II (p = 0.16). No statistically significant differences were noted in terms of gender, age, or laterality between two groups. The mean duration of surgery and the rates of balloon dilatation and postoperative stent placement were higher in group I when compared with group II, and differences were statistically significant (p < 0.05). CONCLUSIONS: In this study, we determined that dURS was a safe method in chronic hemodialysis patients. However, duration of surgery and the rates of balloon dilatation and postoperative stent placement were high in our study. PMID- 26561212 TI - An isoform-specific role of FynT tyrosine kinase in Alzheimer's disease. AB - Alzheimer's disease (AD) is the leading cause of dementia in old age and is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles (NFT). Recent studies suggest that Fyn tyrosine kinase forms part of a toxic triad with beta-amyloid and tau in the disease process. However, it is not known whether Fyn is associated with the pathological features of AD in an isoform-specific manner. In this study, we identified selective up-regulation of the alternative-spliced FynT isoform with no change in FynB in the AD neocortex. Furthermore, gene ontology term enrichment analyses and cell type-specific localization of FynT immunoreactivity suggest that FynT up-regulation was associated with neurofibrillary degeneration and reactive astrogliosis. Interestingly, significantly increased FynT in NFT-bearing neurons was concomitant to decreased FynB immunoreactivity, suggesting an involvement of alternative splicing in NFT formation. Furthermore, cultured cells of astrocytic origin have higher FynT to FynB ratio compared to those of neuronal origin. Lastly, primary rat mixed neuron-astrocyte cultures treated with Abeta25-35 showed selective up-regulation of FynT expression in activated astrocytes. Our findings point to an isoform-specific role of FynT in modulating neurofibrillary degeneration and reactive astrogliosis in AD. Fyn kinase is known to interact with beta-amyloid and tau, and contributes to Alzheimer's disease pathogenesis. In this study, it is shown that the alternatively spliced FynT isoform is specifically up-regulated in the AD neocortex, with no change in FynB isoform. The increased FynT correlated with markers of neurofibrillary degeneration and reactive astrogliosis. In primary mixed cultures, treatment with amyloid peptides specifically up-regulated FynT in activated astrocytes. This study points to altered alternative splicing as a potential pathogenic mechanism in AD. PMID- 26561213 TI - Full-Thickness Skin Burn Caused by Radiofrequency Ablation of a Benign Thyroid Nodule. PMID- 26561214 TI - Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. AB - BACKGROUND: Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. AIM: The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. METHODS: The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. RESULTS: Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). CONCLUSIONS: Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates. PMID- 26561215 TI - Evidence of an association between sign language phonological awareness and word reading in deaf and hard-of-hearing children. AB - BACKGROUND AND AIMS: Children with good phonological awareness (PA) are often good word readers. Here, we asked whether Swedish deaf and hard-of-hearing (DHH) children who are more aware of the phonology of Swedish Sign Language, a language with no orthography, are better at reading words in Swedish. METHODS AND PROCEDURES: We developed the Cross-modal Phonological Awareness Test (C-PhAT) that can be used to assess PA in both Swedish Sign Language (C-PhAT-SSL) and Swedish (C-PhAT-Swed), and investigated how C-PhAT performance was related to word reading as well as linguistic and cognitive skills. We validated C-PhAT-Swed and administered C-PhAT-Swed and C-PhAT-SSL to DHH children who attended Swedish deaf schools with a bilingual curriculum and were at an early stage of reading. OUTCOMES AND RESULTS: C-PhAT-SSL correlated significantly with word reading for DHH children. They performed poorly on C-PhAT-Swed and their scores did not correlate significantly either with C-PhAT-SSL or word reading, although they did correlate significantly with cognitive measures. CONCLUSIONS AND IMPLICATIONS: These results provide preliminary evidence that DHH children with good sign language PA are better at reading words and show that measures of spoken language PA in DHH children may be confounded by individual differences in cognitive skills. PMID- 26561216 TI - Iatrogenic Atrial Septal Defect after Radiofrequency or Cryoballoon Ablation of Atrial Fibrillation. PMID- 26561217 TI - Analysis of the Usefulness of Optical Coherence Tomography and Intravascular Ultrasonography for the Examination of Rabbit Atherosclerotic Plaques. AB - In the present study, we aimed to establish a rabbit atherosclerosis model and examine atherosclerotic plaques by using optical coherence tomography (OCT) and intravascular ultrasonography (IVUS) to evaluate the clinical usefulness of these diagnostic tools in the detection of atherosclerotic plaques. Twenty healthy New Zealand rabbits were fed on a high-fat diet for 4 weeks and then subjected to abdominal aortic intimal injury. The OCT and IVUS were performed after 8 weeks. The distal and proximal plaque images were marked to observe the plaque thickness and features of the lesions at the tunica intima and tunica media. Moreover, a pathological examination was performed to evaluate the efficacies of OCT and IVUS. The mean (SD) plaque thickness on OCT and IVUS images was 386.5 (125.3) MUm and 412.7 (165.8) MUm, respectively. Pathological examinations indicated a mean (SD) plaque thickness of 360.2 (98.l) MUm (P > 0.05). No significant differences were noted between the 2 methods. The intimal and medial thickness measured with OCT showed greater correlation with pathologically measured thickness (r = 0.95, P < 0.001 for OCT; r = 0.88, P < 0.001 for IVUS); in particular, the intimal thickness measurements on OCT showed a higher correlation (r = 0.98, P < 0.001). However, the measurements obtained using IVUS were not accurate. Thus, compared with IVUS, OCT was more accurate in determining the nature and thickness of vascular plaques. PMID- 26561218 TI - The Myriad Advantages of Ultrasonography in Image-Guided Interventions. AB - We will review and illustrate the multiple advantages of ultrasound as an image guidance tool, including real-time vessel visualization, multiplanar capability, portability/availability, and decreased procedure time and cost.We will demonstrate the unique advantages of the use of this imaging modality in the biopsy of small parenchymal lesions particularly those that are not visible with unenhanced computed tomography (CT) or not persistently visible with contrast enhanced CT or those lesions not readily accessible by CT guidance, the use of direct probe compression to displace bowel away from biopsy targets, the use of direct probe compression to staunch intraprocedural bleeding observed with real time visualization to minimize postprocedural bleeding complications, and the ability to biopsy masses in pediatric patients as a function of the inherent lack of ionizing radiation.Finally, we will review and illustrate how the use of preprocedural lesion characterization with ultrasound at times can serve as a problem-solving tool providing an alternative and reasonably confident diagnosis and thus avoiding unnecessary procedures and associated potential risks. PMID- 26561219 TI - SRU Cases of the Day: Plexiform Neurofibroma. PMID- 26561220 TI - Ultrasound of Biliary Cast Syndrome and Its Mimics. AB - Biliary cast syndrome (BCS) consists of mass-like hardened collections of inspissated bile and sloughed biliary mucosa filling the intrahepatic and/or extrahepatic bile ducts, which show an alternating pattern of dilatation and stricture. It is a rare but serious complication of liver transplantation frequently necessitating repeated percutaneous, endoscopic or surgical stent placements, and cast retrieval. Although not typically considered as the modality of choice for BCS compared with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography, ultrasound can be quite useful for this diagnosis. This article reviews the sonographic appearance of BCS in postliver transplant patients and correlates with other imaging modalities including computed tomography, MRCP, and endoscopic retrograde cholangiopancreatography. Also reviewed are other intrahepatic pathologies that mimic the appearance of BCS on ultrasound. PMID- 26561221 TI - Squamous Cell Carcinoma of the Larynx. PMID- 26561222 TI - Abnormal postural reflexes in a patient with pontine ischaemia. AB - The control of body posture is a complex activity that needs a very close relationship between different structures, such as the vestibular system, and the muscle and joint receptors of the neck. Damage of even one of these structures can lead to abnormal postural reflexes. We describe a case of a woman with a left pontine ischaemia who developed a 'dystonic' extensor posture of the left limbs while turned on the right side. This clinical picture differs from previous reports on the subject, and may relate to ischaemic damage of a pontine structure involved in posture control, or of adjacent neural connections to be yet identified. To the best of our knowledge, this is the first case reported in the literature. Clinical examples of an altered interplay between vestibular and neck receptors are rare. PMID- 26561223 TI - Encapsulating peritoneal sclerosis: surgery, sustained drug therapy and treatment of recurrence at 1 year. AB - A 74-year-old woman with end-stage renal disease presented with clinical symptoms of encapsulating peritoneal sclerosis 2 years after switching from peritoneal dialysis to haemodialysis. Imaging revealed a large cystic structure in her abdomen and her final diagnosis was made by exploratory laparotomy. A 10 cm*15 cm fibrous rind was excised from the peritoneum and the patient was subsequently started on tamoxifen 20 mg daily and prednisone 20 mg daily. Given her reduction in clinical symptoms and concerns about the long-term effects of corticosteroids, prednisone was tapered and she remained on tamoxifen monotherapy. 1 year postsurgery, she presented with symptoms of nausea, vomiting and anorexia. A repeat CT of the abdomen confirmed a recurrence of encapsulating peritoneal sclerosis. Prednisone and tamoxifen were restarted at increased dosages of 25 and 40 mg daily, respectively. The patient's symptoms were ameliorated within 2 weeks of drug therapy modification. PMID- 26561224 TI - Phenotypic extremes in liveborn monozygotic twins with mosaic Edwards syndrome. AB - Mosaic trisomy 18 (Edwards syndrome) in monozygotic diamniotic liveborn twins is rare. We describe such a case involving preterm male infants. Although both infants had a low percentage of trisomy 18 cells in peripheral blood leucocytes, their varied phenotypic presentation of mosaic trisomy 18 resulted in one twin surviving, with the other twin's demise at 1 month of age. Despite the presence of trisomy 18 in peripheral leucocytes, further analysis of a buccal smear and skin biopsy of the surviving twin did not show evidence of trisomy 18. Establishing such diagnoses in a timely manner is imperative for the child, parents and clinicians. The clinical course of these twins reflects the unpredictable prognosis associated with the diagnosis of mosaic trisomy 18, and emphasises the challenges that can be encountered when counselling parents. PMID- 26561225 TI - An old 'new' friend: postmeasles blindness in the 21st century. PMID- 26561226 TI - Chiari malformation, syringomyelia and bulbar palsy in X linked hypophosphataemia. AB - X linked hypophosphataemia (XLH) is a rare condition with numerous musculoskeletal complications. It may mimic other more familiar conditions, such as vitamin D deficiency, ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. We describe two cases with Chiari type 1 malformations and syringomyelia, neither of which is well recognised in XLH. The first presented late with the additional complications of spinal cord compression, pseudofracture, renal stones and gross femoroacetabular impingement requiring hip replacement. The second also had bulbar palsy; the first case to be described in this condition, to the best of our knowledge. We wish to raise awareness of the important neurological complications of syringomyelia, Chiari malformation, spinal cord compression and bulbar palsy when treating these patients. We also wish to draw attention to the utility of family history and genetic testing when making the diagnosis of this rare but potentially treatable condition. PMID- 26561227 TI - A rare combination of amniotic constriction band with osteogenesis imperfecta. AB - Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases. PMID- 26561228 TI - An insidious case of hepatic artery pseudoaneurysm secondary to acalculus cholecystitis. AB - A 68-year-old man with expressive dysphasia presented with upper gastrointestinal haemorrhage, jaundice and abdominal pain. He was unable to tolerate ultrasound tranducer pressure. His oesophagogastroduodenoscopy (OGD) showed large blood clots in the stomach with blood trickling from the ampulla. An urgent CT angiogram demonstrated a 32 mm pseudoaneurysm within the gallbladder fossa. The patient subsequently underwent an endovascular embolisation of the pseudoaneurysm performed by the interventional radiology team. PMID- 26561229 TI - Rotator cuff tears in luxatio erecta: an arthroscopic perspective of two cases. AB - Luxatio erecta accounts for only 0.5% of all shoulder dislocations. More than 150 cases have been described in the literature, focusing mainly on the method of reduction and/or associated complications. Some of the well-described complications include injuries to the humeral head, glenoid, clavicle, rotator cuff, capsules and ligaments, brachial plexus and axillary artery/vein. Among these, rotator cuff injuries are reported to occur in about 80% of cases. However, in the majority of instances, cuff injuries have been managed conservatively and have been reported to apparently provide optimal functional outcomes. We report our experience with two cases of luxatio erecta associated with massive rotator cuff injuries, which were evaluated and further managed by arthroscopic repair. The emphasis in these cases is to define cuff injuries and proceed based on patients' age, demands and characteristics of the cuff tears. Arthroscopic evaluation and cuff repairs should be contemplated in these patients, to improve shoulder functions. PMID- 26561230 TI - False-positive uptake on radioiodine whole-body scan due to bronchiectasis. PMID- 26561231 TI - Electrochemical and Dry Sand Impact Erosion Studies on Carbon Steel. AB - This study investigated the dry and aqueous erosion of mild steel using electrochemical and dry sand impact techniques. In dry sand impact experiments, mild steel was eroded with 45 MUm and 150 MUm sand particles. Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and micro-hardness techniques were used to elaborate the surface morphology of the eroded samples. The results revealed significant change in morphology of the eroded samples. In depth analysis showed that although the metal erosion due to larger particles was significantly higher, the fines also notably damaged the metal surface. The surface damages were appreciably reduced with decrease in impact angle of the accelerated particles. The maximum damages were observed at an impact angle of 90 degrees . The hardness of the samples treated with 45 MUm and 150 MUm sand remained in the range of 88.34 to 102.31 VHN and 87.7 to 97.55 VHN, respectively. In electrochemical experiments, a triple electrode probe was added into the metal treatment process. The linear polarization resistance (LPR) measurements were performed in slurries having 5% (by weight) of sand particles. LPR of the samples treated with 45 MUm and 150 MUm sand slurries was calculated about 949 Omega.cm(2) and 809 Omega.cm(2), respectively. PMID- 26561232 TI - Genome-wide association and epistasis studies unravel the genetic architecture of sudden death syndrome resistance in soybean. AB - Soybean [Glycine max (L.) Merr.] is an economically important crop that is grown worldwide. Sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the top yield-limiting diseases in soybean. However, the genetic basis of SDS resistance, especially with respect to epistatic interactions, is still unclear. To better understand the genetic architecture of soybean SDS resistance, genome wide association and epistasis studies were performed using a population of 214 germplasm accessions and 31,914 SNPs from the SoySNP50K Illumina Infinium BeadChip. Twelve loci and 12 SNP-SNP interactions associated with SDS resistance were identified at various time points after inoculation. These additive and epistatic loci together explained 24-52% of the phenotypic variance. Disease resistant, pathogenesis-related and chitin- and wound-responsive genes were identified in the proximity of peak SNPs, including stress-induced receptor-like kinase gene 1 (SIK1), which is pinpointed by a trait-associated SNP and encodes a leucine-rich repeat-containing protein. We report that the proportion of phenotypic variance explained by identified loci may be considerably improved by taking epistatic effects into account. This study shows the necessity of considering epistatic effects in soybean SDS resistance breeding using marker assisted and genomic selection approaches. Based on our findings, we propose a model for soybean root defense against the SDS pathogen. Our results facilitate identification of the molecular mechanism underlying SDS resistance in soybean, and provide a genetic basis for improvement of soybean SDS resistance through breeding strategies based on additive and epistatic effects. PMID- 26561233 TI - Design, Preparation, and Characterization of a Novel Red Long-Persistent Perovskite Phosphor: Ca3Ti2O7:Pr3+. AB - Currently, the development of efficient red-emitting persistent phosphor is still an ongoing challenge. Herein, a novel red-emitting LPL phosphor Ca3Ti2O7:Pr(3+) is successfully prepared by a high-temperature solid-state method. XRD Rietveld refinement analyses demonstrate the high phase purity of the sample which crystallizes in an orthorhombic Ccm21 space group with lattice parameters of a = 5.7702(5) A, b = 19.4829(7) A, and c = 5.1214(2) A. Electronic structure of the host matrix is analyzed by the first-principle calculation using CASTEP code. The calculation results show that Ca3Ti2O7 has a direct band gap with CB and VB mainly composed of the Ti-3d and O-2p states, respectively. On the basis of the DR spectrum, the band gap is determined to be 3.6 eV. It is demonstrated that the 612 nm red-emitting persistent luminescence of Ca3Ti2O7:Pr(3+) can be either activated by Ti(4+)-O(2-) -> Ti(3+)-O(-) host absorption and Pr(3+)-O-Ti(4+) -> Pr(4+)-O-Ti(3+) IVCT in the UV region, or Pr(3+):(3)H4 -> (3)PJ transition in the blue region. The red afterglow can last for ~ 5 min observed by the naked eyes in the dark after ceasing the irradiation source. On the basis of the TL analyses, the trap is found exponentially distributed in the host with the depth of 0.69 0.92 eV. Finally, a possible LPL mechanism for Ca3Ti2O7:Pr(3+) is proposed. PMID- 26561234 TI - Intramolecular, Pd/Cu-Co-catalyzed P-C Bond Cleavage and Addition onto an Alkyne: A Route to Benzophospholes. AB - Under Pd(II)/CuI cocatalysis, o-diarylphosphinophenylalkynes cyclize in boiling toluene via C-P bond cleavage and arylphosphination of the C=C bond. This protocol provides an unprecedented atom- and step-efficient access to optoelectronically and biologically interesting benzophospholes. PMID- 26561235 TI - Memory for Lectures: How Lecture Format Impacts the Learning Experience. AB - The present study investigated what impact the presentation style of a classroom lecture has on memory, mind wandering, and the subjective factors of interest and motivation. We examined if having a professor lecturing live versus on video alters the learning experience of the students in the classroom. During the lectures, students were asked to report mind wandering and later complete a memory test. The lecture format was manipulated such that all the students received two lectures, one live and one a pre-recorded video. Results indicate that lecture format affected memory performance but not mind wandering, with enhanced memory in the live lectures. Additionally, students reported greater interest and motivation in the live lectures. Given that a single change to the classroom environment, professor presence, impacted memory performance, as well as motivation and interest, the present results have several key implications for technology-based integrations into higher education classrooms. PMID- 26561236 TI - The effectiveness of interventions in supporting self-management of informal caregivers of people with dementia; a systematic meta review. AB - BACKGROUND: Informal caregivers of people with dementia are challenged in managing the consequences of dementia in daily life. The objective of this meta review was to synthesize evidence from previous systematic reviews about professional self-management support interventions for this group. METHODS: In March 2014, searches were conducted in PubMed, CINAHL, Cochrane Library, Embase and PsycINFO. The PRISMA Statement was followed. Interventions were grouped using Martin's targets of self-management, covering 5 targets: relationship with family, maintaining an active lifestyle, psychological wellbeing, techniques to cope with memory changes and information about dementia. Using an evidence synthesis, the outcomes from the included interventions were synthesized and conclusions were drawn about the level of evidence for the effectiveness of interventions within each target. RESULTS: Ten high-quality systematic reviews were selected. Evidence exists for the effectiveness of professional self management support interventions targeting psychological wellbeing on stress and social outcomes of informal caregivers. In addition, evidence exists for the effectiveness of interventions targeting information on ability/knowledge. Limited evidence was found for the effectiveness of interventions targeting techniques to cope with memory change on coping skills and mood, and for interventions targeting information on the outcomes sense of competence and decision-making confidence of informal caregivers. CONCLUSIONS: Scientific evidence exists for the effectiveness of a number of professional self-management support interventions targeting psychological wellbeing and information. Health care professionals could take account of the fact that psycho-education was integrated in most of the self-management support interventions that were found to be effective in this meta-review. Furthermore, longer and more intensive interventions were associated with greater effects. PMID- 26561237 TI - Fetal myelomeningocele repair: where are we and where can we go? PMID- 26561238 TI - [Determinants of maternal near miss in an obstetric intensive care unit]. AB - PURPOSE: To evaluate the risk factors for morbidity and mortality in an obstetric intensive care unit at a university hospital. METHODS: Observational cross sectional study with 492 pregnant/puerperal women. Patients were admitted to the obstetric intensive care unit over a period of one year, being informed about the proposals of the study and a questionnaire was applied. The analysis was performed using Microsoft Excel 2013 and GraphPad Prism 6. To evaluate risk factors, chi2 tests were used. RESULTS: The main risk factors to near miss were: non-white race (OR=2.5; PR=2.3); marital status (married women) (OR=7.9; PR=7.1), schooling (primary) (OR=3.1; PR=2.8), being from the countryside (OR=4.6; PR=4.0), low income (OR=70; PR=5.5), gestational hypertensive disorders (OR=16.3; PR=13.2), receiving prenatal care (OR=5.0; PR=4.254) and C-section before labor (OR=39.2; PR=31.2). CONCLUSIONS: The prevalence of near miss was associated with socioeconomic/clinical factors and care issues, revealing the importance of interventions to improve these indicators. Additionally, we suggest a better curriculum insertion of this subject in the discipline of the medical course due to the importance of avoiding the near miss using adequate medical education. The importance of correct prenatal care is emphasized in order to identify potential risks, to provide nutritional support to pregnant women, to treat potential diseases and to establish a maternal immunization program, as well as providing better care regarding the clinical features of the patients, in order to reduce obstetrical and neonatal risk. PMID- 26561239 TI - [Risk factors associated among anemia in pregnancy women of network public health of a capital of Brazil Northeastern]. AB - PURPOSE: To evaluate the factors associated with anemia among pregnant women receiving public health care in a capital city in Northeastern Brazil. METHODS: This was a cross-sectional study conducted on a sample of 428 patients obtained on the basis of the estimated prevalence of anemia during pregnancy (50%), a 95% confidence interval (95%CI), an error of 5% and a sample loss of 20%. Pregnant women who lived in the city and were served by the municipal public health network were considered to be eligible for the study. Socioeconomic, lifestyle, clinical and anthropometric data and dietary iron intake were obtained, and capillary hemoglobin was determined. Anemia was identified as a hemoglobin level <11 g/dL, and its association with risk factors was tested using multivariate Poisson regression analysis, with the results expressed as the Prevalence Ratio (PR) and 95%CI. RESULTS: The prevalence of anemia was 28.3% and was higher among women with more members in the household (PR=1.49; 95%CI 1.01-2.22; p=0.046) and those living with food insecurity (PR=1.43; 95%CI 1.00-2.04; p=0.047). CONCLUSION: The prevalence of anemia among pregnant women receiving care from the public health system of the city is a moderate public health problem, requiring the planning of effective measures for its control. PMID- 26561240 TI - Functional activity of neutrophilic polymorphonuclear leukocytes in the first five days postpartum. AB - PURPOSE: To assess the chemotactic activity and phagocytic response of neutrophilic polymorphonuclear leukocytes among women in the first five days postpartum. METHODS: A prospective, cross-sectional clinical-laboratory study was conducted. Data of 31 postpartum women during the first five days after vaginal delivery were compared with those of 24 healthy non-pregnant non-postpartum women matched for age. The inclusion criteria were postpartum, clinically and obstetrically healthy women; vaginal delivery, singleton pregnancy carried to term; non-hypertensive, hyperglycemic, allergic, malnourished or with autoimmune or neoplastic diseases; not having received vaccines or blood products in the last three months. The Control Group was chosen according to the same inclusion criteria but involving non-pregnant non-postpartum women. The chemotactic activity of neutrophilic polymorphonuclear leukocytes was assessed by determining the distance from directed migration to bacterial lipopolysaccharide, in three Boyden chamber assays. The phagocytic response was identified by assessing the Zymosan particles' ingestion in three assays carried out in Leighton tubes. The Student's t-test was used in the statistical analysis, adopting a 5% level of significance. RESULTS: The chemotactic activity of neutrophilic polymorphonuclear leukocytes from postpartum women in the presence of homologous (73.2 +/- 6.9) and autologous (78.6 +/- 13.9) sera showed a significant increase compared to the values observed in the Control Group (64.1 +/- 4.1 and 66.6 +/- 5.4). Both chemotactic response and phagocytosis ingestion phase of neutrophilic polymorphonuclear leukocytes were significantly increased (p < 0.05) in postpartum women compared to healthy non-pregnant and non-postpartum women. CONCLUSION: There was an increase in the chemotactic activity and phagocytic response of neutrophilic polymorphonuclear leukocytes during the first five days after vaginal delivery in women. PMID- 26561241 TI - Polymorphism in the lymphotoxin-alpha gene, position +252 (rs909253), is not associated with preeclampsia development in Brazilian women. AB - PURPOSE: To investigate the frequencies of polymorphic allele and genotypes for the LT-alpha gene, position +252 (rs909253), in Brazilian women with preeclampsia. METHODS: This is a case-control study, in which 30 women with preeclampsia, classified according to the criteria of the National High Blood Pressure Education Program, and 115 women in the control group, with at least two healthy pregnancies, were selected. Peripheral blood was collected, and DNA was extracted, followed by genotyping, using specific primers and restriction analysis. The genotypes obtained were AA, AG and GG. Statistical analysis was performed using the chi2 association test. The Hardy-Weinberg Equilibrium was tested using the Haploview Program. RESULTS: The results showed no association between genotypes and preeclampsia development (chi2=2.0; p=0.4). When the AG and GG genotypes were grouped according to allele G presence or absence (genotype AA), the data showed that the presence of allele G was not significantly different between cases (women with preeclampsia) and controls (chi2=0.0; p=1.0). The LT-alpha gene polymorphism, position +252 (rs909253), seems not to be an important candidate for the development of preeclampsia. Other inflammatory genes should be researched, and studies involving gene-environment interactions should be performed, in order to reach a better understanding of the etiology of the preeclampsia. PMID- 26561242 TI - [Translation, adaptation and validation of the Brazilian version of the Utian Quality of Life for evaluation of quality of life in the climacteric]. AB - PURPOSE: To translate, to adapt and to validate the Utian Quality of Life (UQOL) for the Brazilian population. METHODS: Women in the climacteric phase, residents in the city of Natal, Rio Grande do Norte, located in the Brazilian Northeast, were randomly selected. UQOL and SF-36 questionnaires were used, and the translation from English to Portuguese was made by three teachers, while the adaptation stage of the translated version was made by applying the questionnaire to 35 women, which could mark the answer choice "I did not understand the question"; reproducibility measurements (test-retest) and construct validity were used to validate, following international methodological standards. RESULTS: The Brazilian version was fully recognized by the target population, which was comprised of 151 women, as no question showed a percentage of "non-understanding" equal to or greater than 20%. The results for intra and interobserver reproducibility demonstrated significant agreement on all the questionnaire items. This version showed consistency above the required criteria (>70), demonstrating its accuracy, while the construct validity was obtained by statistically significant correlations between the domains occupation, health and emotional of UQOL and the SF-36 domains. The Cronbach's alpha coefficient for the whole instrument was 0.82, representing good accuracy. Item-total correlation analysis showed the scale homogeneity. CONCLUSION: From the steps taken, the UQOL questionnaire was translated and adapted for its use in Brazil, with high reproducibility and validity. Thus, it can be included and used in Brazilian studies that aim at evaluating the quality of life of women during the peri- and postmenopausal. PMID- 26561243 TI - [Postpartum Takotsubo cardiomyopathy: case report]. AB - Takotsubo cardiomyopathy is characterized by acute and transient dysfunction of the apical segment of the left ventricle usually after an intense physical or emotional stress, mimicking an acute coronary syndrome. Because this is a rare syndrome, the differential diagnosis is particularly important and a high level of suspicion is essential. Obstetricians should be aware to diagnose and deal with this unexpected event. Treatment is essentially supportive, with spontaneous and complete reversal of the changes within days or weeks. The occurrence of complications may dictate a less benign prognosis. We report a case of Takotsubo cardiomyopathy in a 39-year-old woman who underwent Cesarean delivery. She presented with bradycardia, chest pain and pulmonary edema immediately after the delivery. Her echocardiography showed and apical ballooning. Cardiac biomarkers and electrocardiogram were altered and echocardiogram showed severe left ventricular dysfunction with hypokinesia of the anterior wall. Coronary angiography excluded obstructive coronary artery disease. PMID- 26561244 TI - [Limitations and controversies in determining the predictive value of oocyte and embryo morphology criteria]. AB - In order to increase the success rate of in vitro fertilization cycles, several studies have focused on the identification of the embryo with higher implantation potential. Despite recent advances in the reproductive medicine, based on the OMICs technology, routinely applicable methodologies are still needed. Thus, in most fertilization centers embryo selection for transfer is still based on morphological parameters evaluated under light microscopy. Several morphological parameters may be evaluated, ranging from the pronuclear to blastocyst stage. In general, despite the day of transfer, some criteria are suggested to present a predictive value for embryo viability when analyzed independently or combined. However, the subjectivity of morphological evaluation, as well as the wide diversity of embryo classification systems used by different fertilization centers shows contrasting results, making the implementation of a consensus regarding different morphological criteria and their predictive value a difficult task. The optimization of embryo selection represents a large potential to increase treatment success rates, allowing the transfer of a reduced number of embryos and minimizing the risks of multiple pregnancy. PMID- 26561245 TI - Infant product-related injuries: comparing specialised injury surveillance and routine emergency department data. AB - OBJECTIVE: To explore the potential for using a basic text search of routine emergency department data to identify product-related injury in infants and to compare the patterns from routine ED data and specialised injury surveillance data. METHODS: Data was sourced from the Emergency Department Information System (EDIS) and the Queensland Injury Surveillance Unit (QISU) for all injured infants between 2009 and 2011. A basic text search was developed to identify the top five infant products in QISU. Sensitivity, specificity, and positive predictive value were calculated and a refined search was used with EDIS. Results were manually reviewed to assess validity. Descriptive analysis was conducted to examine patterns between datasets. RESULTS: The basic text search for all products showed high sensitivity and specificity, and most searches showed high positive predictive value. EDIS patterns were similar to QISU patterns with strikingly similar month-of-age injury peaks, admission proportions and types of injuries. CONCLUSIONS: This study demonstrated a capacity to identify a sample of valid cases of product-related injuries for specified products using simple text searching of routine ED data. IMPLICATIONS: As the capacity for large datasets grows and the capability to reliably mine text improves, opportunities for expanded sources of injury surveillance data increase. This will ultimately assist stakeholders such as consumer product safety regulators and child safety advocates to appropriately target prevention initiatives. PMID- 26561246 TI - Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis. AB - PURPOSE: Children with Hirschsprung disease (HD) who have a history of enterocolitis (HAEC) have a shift in colonic microbiota, many of which are necessary for short chain fatty acid (SCFA) production. As SCFAs play a critical role in colonic mucosal preservation, we hypothesized that fecal SCFA composition is altered in children with HAEC. METHODS: A multicenter study enrolled 18 HD children, abstracting for history of feeding, antibiotic/probiotic use, and enterocolitis symptoms. HAEC status was determined per Pastor et al. criteria (12). Fresh feces were collected for microbial community analysis via 16S sequencing as well as SCFA analysis by gas chromatography-mass spectrometry. RESULTS: Nine patients had a history of HAEC, and nine had never had HAEC. Fecal samples from HAEC children showed a 4-fold decline in total SCFA concentration vs. non-HAEC HD patients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAEC children. Finally, we measured relative abundance of SCFA-producing fecal microbiota. Interestingly, 10 of 12 butyrate-producing genera as well as 3 of 4 acetate-producing genera demonstrated multi-fold expansion. CONCLUSION: Children with HAEC history have reduced fecal SCFAs and altered SCFA profile. These findings suggest a complex interplay between the colonic metabolome and changes in microbiota, which may influence the pathogenesis of HAEC. PMID- 26561247 TI - Long-term outcomes and sex differences after restorative proctocolectomy in pediatric patients with ulcerative colitis. AB - BACKGROUND: Restorative proctocolectomy (RPC) for ulcerative colitis (UC) could result in a higher patient quality of life, avoiding frequent disease flares; however, pouch failures and pouch-related complications (PRCs) can develop. PURPOSE: No cohort studies have examined pouch failure and the differences between adult and pediatric patients or the sex differences in pediatric UC. Therefore, the pouch failure rates were compared between adults and pediatric patients, and pouch failure and PRCs in pediatric UC were evaluated. METHODS: UC patients who underwent RPC between January 1987 and June 2014 at Hyogo College of Medicine were included. Patient background characteristics, PRCs, and pouch failure were reviewed. RESULTS: A total of 1347 adult UC patients and 90 (51 boys, 39 girls) pediatric UC patients were included in the study. The cumulative rate of pouch failure at 10years after RPC was significantly higher in pediatric UC (9.5%) than in adult UC (2.1%; p<0.01). In pediatric UC, the independent risk factors for pouch failure were pouchitis (hazard ratio (HR) 19.3) and anal fistula (HR 5.5). Although a sex difference was not seen in pouch failure, an independent risk factor for PRCs was being a girl (HR 2.5). CONCLUSIONS: Pouch failure was more common in pediatric than in adult UC. PRCs after RPC were more common in girls in pediatric UC. PMID- 26561248 TI - Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients. AB - PURPOSE: Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. METHODS: After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. RESULTS: Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). CONCLUSIONS: Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure. PMID- 26561250 TI - Molecular and epigenetic basis of macrophage polarized activation. AB - Macrophages are unique cells for origin, heterogeneity and plasticity. At steady state most of macrophages are derived from fetal sources and maintained in adulthood through self-renewing. Despite sharing common progenitors, a remarkable heterogeneity characterized tissue-resident macrophages indicating that local signals educate them to express organ-specific functions. Macrophages are extremely plastic: chromatin landscape and transcriptional programs can be dynamically re-shaped in response to microenvironmental changes. Owing to their ductility, macrophages are crucial orchestrators of both initiation and resolution of immune responses and key supporters of tissue development and functions in homeostatic and pathological conditions. Herein, we describe current understanding of heterogeneity and plasticity of macrophages using the M1-M2 dichotomy as operationally useful simplification of polarized activation. We focused on the complex network of signaling cascades, metabolic pathways, transcription factors, and epigenetic changes that control macrophage activation. In particular, this network was addressed in sepsis, as a paradigm of a pathological condition determining dynamic macrophage reprogramming. PMID- 26561249 TI - Can congenital pulmonary airway malformation be distinguished from Type I pleuropulmonary blastoma based on clinical and radiological features? AB - BACKGROUND: The management of congenital cystic lung lesions is controversial. Arguments for routine resection during infancy include the possibility of the lesion being Type I pleuropulmonary blastoma (PPB) rather than a cystic congenital pulmonary airway malformation (CPAM). We aimed to identify clinical and radiological features that might distinguish between CPAM and PPB and to develop a diagnostic algorithm based on these features. METHODS: All recorded cases of Type I PPB were retrieved from the International PPB Registry and compared with an institutional cohort of children undergoing resection of CPAM (2002-2013) that was noted at some stage to be at least partially cystic. Regression models were created to identify variables that might differentiate CPAM from PPB. Odds ratio (OR) and positive predictive value (PPV) were calculated for each variable and a decision algorithm developed. RESULTS: In 112 cases of Type I PPB and 103 of CPAM, factors favoring a diagnosis of CPAM included prenatal detection (OR 89.4), systemic feeding vessel (OR 61.7), asymptomatic (OR 8.0), and hyperinflated lung (OR 6.6). Factors favoring a diagnosis of PPB included bilateral or multisegment involvement (OR 2.4). A decision algorithm that helps to identify lesions requiring resection and those which can be safely observed is presented. CONCLUSION: Clinical and radiological features can help to differentiate between CPAM and PPB. Our algorithm allows identification of children at higher risk of PPB in whom we would recommend resection and those at low risk in whom continued close observation is safe. PMID- 26561252 TI - Fabrication of Amperometric Glucose Sensor Using Glucose Oxidase-Cellulose Nanofiber Aqueous Solution. AB - Cellulose nanofiber aqueous solution, which remained virtually transparent for more than one week, was prepared by using the clear upper layer of diluted cellulose nanofiber solution produced by wet jet milling. Glucose oxidase (GOx) was easily dissolved in this solution and GOx-immobilized electrode was easily fabricated by simple repetitious drops of GOx-cellulose solution on the surface of a platinum-iridium electrode. Glucose sensor properties of the obtained electrodes were examined in phosphate buffer solution of pH 7.4 at 40 degrees C. The obtained electrode provided a glucose sensor response with significantly high response speed and good linear relationship between glucose concentration and response current. After an initial decrease of response sensitivity for a few days, relatively constant sensitivity was obtained for about 20 days. Nevertheless, the influence of electroactive compounds such as ascorbic acid, uric acid and acetoaminophen were not negletable. PMID- 26561251 TI - Aryl hydrocarbon receptor: Linking environment to immunity. AB - Mucosal and barrier tissues are unique in that they mediate crosstalk between the host and the surrounding environment, which contains many potentially harmful factors. Therefore, it is critical that cell types present at barrier and mucosal surfaces are equipped with mechanisms to sense changes in the environment and to calibrate their responses accordingly. Aryl Hydrocarbon Receptor (AHR) is a ligand dependent transcription factor well known to generate biological responses to environmental pollutants, such as benzo{a}pyrene and halogenated dioxins. Surprisingly, in the last few years a large body of evidence has shown that AHR is also involved in maintaining homeostasis or in triggering pathology by modulating the biological responses of critical cell types at the barrier and mucosal interfaces. Here, we will review progresses in this field and discuss how targeting AHR activation may impact disease. PMID- 26561254 TI - "Recent Progress in High Performance Separation". PMID- 26561253 TI - Pyridinium-based Task-specific Ionic Liquid with a Monothioether Group for Selective Extraction of Class b Metal Ions. AB - A pyridinium-based task-specific ionic liquid (TSIL) with a monothioether group, [3-TPPy][NTf2], extracted typical class b metal ions, such as Ag(I), Cu(I), Pd(II), and Pt(II), in high selectivity. It was found that the composition ratio of the extracted Ag(I) and Cu(I) species depended on the TSIL concentration, and that TSIL extracted these metal ions through mono-S-coordinated complex formation at low TSIL concentrations. [3-TPPy][NTf2] can be recycled in the extraction recovery process, which is of a great advantage for practical use in environmentally benign separation methods. PMID- 26561255 TI - Capillary Electrophoresis with Laser-induced Fluorescence Detection for Application in Intracellular Investigation of Anthracyclines and Multidrug Resistance Proteins. AB - Capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) is a powerful method for the trace analysis of cellular components. This review presents a summary of topics for the direct analysis of anthracyclines and multidrug resistance proteins in cancerous cells. A micellar electrokinetic chromatography (MEKC) method that does not use organic solvents, and hence prevents the precipitation of proteins in cellular samples, was shown to be a reliable method for the determination of several anthracyclines including the epimeric doxorubicin and epirubicin. A fast CE-based immunoassay for investigating transporter multidrug resistance associated protein (MRP1) was also developed for routine or explorative analysis of the levels of transporter proteins in cancerous cells. A combination of the developed MEKC-LIF method and the CE immunoassay (CEIA) method has permitted the analysis of anthracyclines and MRP1 in a cell line to show the relationship between the levels of MRP1 and amount of anthracyclines in cancerous cells. PMID- 26561256 TI - Development of a Fully-automated On-line Oxidation Column-switching HPLC System for the Determination of Endogenous Melatonin in Human Clinical Samples. AB - A fully-automated on-line oxidation column-switching HPLC system has been developed for the determination of endogenous melatonin in human plasma and saliva. This HPLC system consists of four processes. In the first step, melatonin is fractionated using a reversed-phase C4 column (Proteonavi, 75 mm * 1.0 mm i.d.). In the second step, the obtained melatonin fraction is on-line collected, and oxidized to a highly-fluorescent compound, N-[(6-methoxy-4-oxo-1,4 dihydroquinolin-3-yl)methyl]acetamide (6-MOQMA), by mixing with hydrogen peroxide under alkaline conditions. In the third step, the produced 6-MOQMA is concentrated, and the oxidation reagents are removed using an alkaline resistive reversed-phase column, Asahipak ODP (35 mm * 1.0 mm i.d.). In the final fourth step, the 6-MOQMA is determined by a microbore-ODS column packed with ultrafine particles (CAPCELL PAK C18 IF, 250 mm * 1.0 mm i.d.). The limit of detection of melatonin using this system is about 200 amol/injection, and the determination of endogenous melatonin in a small volume of human physiological fluids, such as 100 MUL of plasma and 300 MUL of saliva, was successfully accomplished. PMID- 26561257 TI - Preconcentration of Aromatic Compounds in Aqueous Samples with a Polymer-coated Fiber-packed Capillary and Subsequent Temperature-programmed Elution with Water for Pseudo-2D LC Separations. AB - A bundle of polymer-coated filaments was successfully introduced as an extraction medium for the preconcentration of an aqueous solution of aromatic compounds. The extraction was simply carried out with pumping the aqueous sample solution to the extraction capillary at ambient temperature. The extracted analytes were sequentially eluted with a flow of pure water using temperature-programmed heating of the extraction capillary in an oven. The results clearly suggest that the polymer-coated fiber-packed capillary could be employed in the sample preparation process for the analysis of various aqueous samples. Introducing the fractions eluted from the fiber-packed capillary to a conventional microcolumn liquid chromatography (micro-LC) system via a home-made valve-based modulator, an on-line coupled extraction/separation system was developed and a possibility to a pseudo-two-dimensional (pseudo-2D) LC separation of aromatic compounds in aqueous matrices has also been demonstrated. PMID- 26561258 TI - Affinity Capillary Electrophoresis for Selective Control of Electrophoretic Mobility of Sialic Acid Using Lanthanide-Hexadentate Macrocyclic Polyazacarboxylate Complexes. AB - It is difficult to control the electrophoretic mobility in order to obtain high resolution among saccharides in complex samples. We report herein on a new affinity capillary electrophoresis (ACE) method for an anionic monosaccharide, N acetylneuraminic acid (Neu5Ac), which is important in terms of pathological diagnosis, using lanthanide-hexadentate macrocyclic polyazacarboxylate complexes (Ln-NOTA) as affinity reagents. It was shown that Ln-NOTA complexes increased the anionic mobility of Neu5Ac by approximately 40% through selective complexation with Neu5Ac. The extent of change in the mobility strongly depended on the type of central metal ion of Ln-NOTA. The stability constant (K) of Lu-NOTA with Neu5Ac was determined by ACE to be log Kb = 3.62 +/- 0.04, which is the highest value among artificial receptors for Neu5Ac reported so far. Using this ACE, the Neu5Ac content in a glycoprotein sample, alpha1-acid glycoprotein (AGP), was determined after acid hydrolysis. Complete separation between Neu5Ac and hydrolysis products was successful by controlling the mobility to determine the concentration of Neu5Ac. PMID- 26561259 TI - Zone Sharpening of Peptides in Pressurized Capillary Electrochromatography Using Dynamic pH Junction. AB - In HPLC, analytes injected into a separation column broaden naturally during the separation procedure. In this paper, analyte zone sharpening of peptides was achieved in pressurized capillary electrochromatography, which is a separation method that combines capillary HPLC and capillary electrophoresis (CE), by employing dynamic pH junction for CE. When the pH of the mobile phase was altered from basic to acidic in a step gradient, the analyte peptides were focused at the basic/acidic interface with the application of voltage. The effect of both pH and pressurized flow velocity on the zone sharpening was investigated. With the proposed method, the peak height of angiotensin II, [Asn(1), Val(5)]-angiotensin II, and angiotensin III were enhanced 12, 10, and 12 times, respectively. Selective peak zone sharpening for angiotensin II was also demonstrated. PMID- 26561260 TI - Highly Sensitive and Multiple Enzyme Activity Assay Using Reagent-release Capillary-Isoelectric Focusing with Rhodamine 110-based Substrates. AB - In this study, a simple and highly sensitive enzyme activity assay based on reagent-release capillary-isoelectric focusing is described. Reagent-release capillaries containing a fluorescent substrate, which produces fluorescent products possessing an isoelectric point after reaction with enzymes, provides a simple procedure. This is because it allows to spontaneously inject a sample solution into the capillary by capillary action, mixing reagents, and subsequently concentrating the fluorescent products based on isoelectric focusing. Fluorescent rhodamine 110 and its monoamide derivative, which were generated as a final product and an intermediate, respectively, were then focused and separated by reagent-release capillary-isoelectric focusing. After 30 min of enzyme reactions, two focused fluorescent bands were clearly isolated along the prepared capillaries. Employing the focused band of rhodamine 110 monoamide allowed for highly sensitive detection of enzyme activity in the 10 pg mL(-1) order, while that of the conventional assay using a microplate was in the ng mL( 1) order. Furthermore, arraying reagent-release capillaries of different substrates on a chip allowed for simultaneous multi-assay of enzyme activity with good sensitivity in the pg mL(-1) order for each protein. PMID- 26561261 TI - A Portable Liquid Chromatograph with a Battery-operated Compact Electroosmotic Pump and a Microfluidic Chip Device with a Reversed Phase Packed Column. AB - A compact and lightweight liquid chromatography system is presented with overall dimensions of 26 cm width * 18 cm length * 21 cm height and weight of 2 kg. This system comprises a battery-operated compact electroosmotic pump, a manual injector, a microfluidic chip device containing a packed column and an electrochemical detector, and a USB bus-powered potentiostat. The pumping system was designed for microfluidic-based reversed-phase liquid chromatography in which an electroosmotically generated water stream pushes the mobile phase via a diaphragm for the output. The flow rate ranged from 0 to 10 MUL/min and had a high degree of precision. The pumping system operated continuously for over 24 h with dry batteries. The column formed in the microfluidic device was packed with 3-MUm ODS particles with a length of 30 mm and a diameter of 0.8 mm. The results presented herein demonstrate the performance of the pumping system and the column using alkylphenols, catecholamine, catechin, and amino acids. PMID- 26561262 TI - Simple and Rapid Immobilization of Coating Polymers on Poly(dimethyl siloxane) glass Hybrid Microchips by a Vacuum-drying Method. AB - A simple and rapid vacuum-drying modification method was applied to several neutral and charged polymers to obtain coating layers for controlling electroosmotic flow (EOF) and suppressing sample adsorption on poly(dimethyl siloxane) (PDMS)-glass hybrid microchips. In the vacuum-dried poly(vinylpyrrolidone) coating, the electroosmotic mobility (MUeo) was suppressed from +2.1 to +0.88 * 10(-4) cm(2)/V.s, and the relative standard deviation (RSD) of MUeo was improved from 10.2 to 2.5% relative to the bare microchannel. Among several neutral polymers, poly(vinylalcohol) (PVA) and poly(dimethylacrylamide) coatings gave more suppressed and repeatable EOF with RSDs of less than 2.3%. The vacuum-drying method was also applicable to polyanions and polycations to provide accelerated and inversed EOF, respectively, with acceptable RSDs of less than 4.9%. In the microchip electrophoresis (MCE) analysis of bovine serum albumin (BSA) in the vacuum-dried and thermally-treated PVA coating channel, an almost symmetric peak of BSA was obtained, while in the native microchannel a significantly skewed peak was observed. The results demonstrated that the vacuum dried polymer coatings were effective to control the EOF, and reduced the surface adsorption of proteins in MCE. PMID- 26561263 TI - Separation of Metal Complexes with Counter Ions by Tube Radial Distribution Chromatography Using a Ternary Solvent Containing 8-quinolinol. AB - An open-tubular capillary chromatography system (tube radial distribution chromatography, TRDC) was developed using a ternary solvent (water-acetonitrile ethyl acetate; volume ratio, 3:8:4) containing 10 mmol L(-1) 8-quinolinol for the separation of nitrate, chloride, and sulfate compounds of Ni(II), Al(III), and Fe(III). When a mixed solution of the Ni(II) compounds was injected into an untreated fused-silica capillary tube (90 cm * 75 MUm i.d.) with a ternary solvent flow rate of 0.8 MUL min(-1), the compounds were eluted in the following order: [Ni(II)-(8-quinolinol)3] complex, [Ni(II)-(8-quinolinol)]-nitrate ion interaction complex, [Ni(II)-(8-quinolinol)]-chloride ion interaction complex, and [Ni(II)-(8-quinolinol)]-sulfate ion interaction complex. The elution of mixtures of the Al(III) and Fe(III) compounds showed similar trends. PMID- 26561264 TI - Development of a Mesoscale Pulsed Discharge Helium Ionization Detector for Portable Gas Chromatography. AB - Miniaturization of gas chromatography (GC) instrumentation enables field detection of volatile organic compounds (VOCs) for chembio-applications such as clandestine human transport and disease diagnostics. We fabricated a mesoscale pulsed discharge helium ionization detector (micro-PDHID) for integrating with our previously described mini-GC hardware. Stainless steel electrodes fabricated by photochemical etching and electroforming facilitated rapid prototyping and enabled nesting of inter-electrode insulators for self-alignment of the detector core during assembly. The prototype was ~10 cm(3) relative to >400 cm(3) of a commercial PDHID, but with a comparable time to sweep a VOC peak from the detector cell (170 ms and 127 ms, respectively). Electron trajectory modeling, gas flow rate, voltage bias, and GC outlet location were optimized for improving sensitivity. Despite 40-fold miniaturization, the micro-PDHID detected 18 ng of the human emanation, 3-methyl-2-hexenoic acid with <3-fold decrease in sensitivity relative to the commercial detector. The micro-PDHID was rugged and operated for 9 months without failure. PMID- 26561265 TI - Simple Pretreatment and HILIC Separation for LC-ESI-MS/MS Determination of Adenosine in Human Plasma. AB - A simple pretreatment method and separation mode for the LC-ESI-MS/MS determination of adenosine in human plasma have been developed. Deproteinization by acetonitrile and ultrafiltration followed by chromatographic separation with a hydrophilic interaction chromatographic (HILIC) column give a highly sensitive MS/MS response without ionic suppression caused by the matrix compounds in human plasma. In addition, the presence of ammonium acetate in the mobile phase contributes to high sensitivity in MS/MS detection, facilitating the ionization of adenosine. This method seems to be amenable to the treatment of many samples in clinical practice. PMID- 26561266 TI - Determination of Acid Dissociation Constant of Pravastatin under Degraded Conditions by Capillary Zone Electrophoresis. AB - The acid dissociation constant of pravastatin was determined under degraded conditions. Pravastatin was degraded in an acidic solution (pH = 2.0) for 5 h, and the degradation solution was subjected to the measurement of the effective electrophoretic mobility by capillary zone electrophoresis. Although the amount of pravastatin decreased by the acid degradation, its acid dissociation constant was successfully determined with the residual pravastatin through its effective electrophoretic mobility. The determined acid dissociation constant value agreed well with the one obtained with freshly prepared solution and with some reported values. PMID- 26561267 TI - Micropillars Fabricated on Poly(methyl methacrylate) Substrates for Separation of Microscale Objects. AB - Development of polymeric microfluidic devices has played an important role in the recent, rapid progress of biomedical research. Here we report a fabrication method for micropillars on poly(methyl methacrylate) (PMMA) substrates for separation of microscale objects. The fabricated micropillars enable continuous separation of microparticles only by introducing fluids. The present method offers a new strategy to fabricate polymeric prototype devices for R&D work. PMID- 26561268 TI - Reversed-phase Chromatography in an Extended Nanospace: Separating Amino Acids in Short and Long Nanochannels. AB - Micro- and nanofluidics has attracted much attention, particularly concerning single-cell analysis when small amounts of liquids are examined. In present work we successfully fabricated extended-nano channels that were more narrow and shorter (2 mm) as well as wider and longer (10 mm), and accomplished a reversed phase HPLC separation of labeled amino acids on these channels after octadecylsilylation (ODS). The separation performance characteristics were compared for both types of nano spaces. At an equal amount of pressure, the longer extended-nano channels showed permeability that was one-order higher (K = 47 * 10(-14) m(2)) and separation impedance (E = 13) that was one-order lower than that of the shorter version. Also, the separation plate number for the longer channel was 4000 with a plate height of 2.5 MUm. Both channels have advantages for use in single-cell analysis. The longer channel can be applied for the separation of macromolecules (proteomics), while the short version is more applicable to small molecules (amino acids). PMID- 26561270 TI - Identification of the silkworm quail gene reveals a crucial role of a receptor guanylyl cyclase in larval pigmentation. AB - Diverse color patterns on the integument of lepidopteran larvae play important roles in their survival through camouflage, mimicry, sexual signaling, and aposematism. In the silkworm Bombyx mori, many color pattern variations have been preserved in inbred strains making them a good model for elucidating the molecular mechanisms that underlie color pattern formation. In this study, we focused on the silkworm quail (q) mutant, which exhibits abnormalities in multiple pigment biosynthesis pathways. Positional cloning of the q gene revealed that disruption of a guanylyl cyclase gene, BmGC-I, is responsible for its abnormal pigmentation. In q mutants, we identified a 16-bp deletion in the BmGC-I transcript, resulting in the production of a premature stop codon. Knockout of the BmGC-I gene resulted in the q-like abnormal pigmentation, thereby demonstrating that the BmGC-I gene is involved in the pigment biosynthesis pathway in the integument. Moreover, quantitative reverse transcription polymerase chain reaction showed that BmGC-I was strongly expressed in the fourth instar on day 2. Our results suggest that BmGC-I deficiency affects the pigment biosynthesis pathway, which supports the involvement of guanylyl cyclase in larval coloration. PMID- 26561271 TI - Economic analysis of uricase production under uncertainty: Contrast of chromatographic purification and aqueous two-phase extraction (with and without PEG recycle). AB - Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two-phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling does not impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques. PMID- 26561273 TI - Montreal cognitive assessment and analysis of related factors for cognitive impairment in patients with chronic cerebral circulation insufficiency. AB - BACKGROUND: Chronic cerebral circulation insufficiency (CCCI) refers to cerebral dysfunctions that lead to cerebral vascular pathological changes. Our aim is to identify factors related to cognitive impairment in CCCI. METHODS: CCCI patients (n=102) were assessed with the Montreal cognitive assessment (MoCA) to analyze cognitive impairment. Patients were divided into two groups according to MoCA scores: (1) cognitive dysfunction and (2) normal cognitive function. We compared the clinical information with univariate and multivariate logistic regression analyses and identified major risk factors related to cognitive impairment in CCCI. RESULTS: Age (p=0.007, OR=3.768, chi2=7.173), leukoaraiosis (p=0.002, OR=6.231, chi2=9.478), a history of hypertension (p=0.021, OR=3.078, chi2=5.307), a history of hyperlipidemia (p=0.016, OR=3.429, chi2=5.795), and the number of vascular risk factors (p=0.019, chi2=9.921) were related to cognitive impairment by univariate analysis. Age (p=0.070, OR=2.689, 95% CI=0.923+/-7.837) and leukoaraiosis (p=0.012, OR=4.531, 95% CI=1.401+/-14.667) were significant by multivariate logistic regression analysis. Age (r=-0.585, p<0.01) had a marked negative correlation with MoCA scores. There were significant differences in the MoCA subscale scores, including visuospatial and executive capacity (p<0.01), attention and calculation (p<0.01), and delayed recall (p<0.01), in patients with different degrees of leukoaraiosis. Patients with CCCI had a higher incidence of cognitive impairment (78.4%). CONCLUSIONS: Changes in visuospatial and executive capacity, delayed recall, and language function represent cognitive manifestations in CCCI. Age and leukoaraiosis have the strongest effects on cognitive impairment morbidity and can aggravate cognitive impairment. PMID- 26561272 TI - Lifespan and Healthspan: Past, Present, and Promise. AB - The past century was a period of increasing life expectancy throughout the age range. This resulted in more people living to old age and to spending more years at the older ages. It is likely that increases in life expectancy at older ages will continue, but life expectancy at birth is unlikely to reach levels above 95 unless there is a fundamental change in our ability to delay the aging process. We have yet to experience much compression of morbidity as the age of onset of most health problems has not increased markedly. In recent decades, there have been some reductions in the prevalence of physical disability and dementia. At the same time, the prevalence of disease has increased markedly, in large part due to treatment which extends life for those with disease. Compressing morbidity or increasing the relative healthspan will require "delaying aging" or delaying the physiological change that results in disease and disability. While moving to life expectancies above age 95 and compressing morbidity substantially may require significant scientific breakthroughs; significant improvement in health and increases in life expectancy in the United States could be achieved with behavioral, life style, and policy changes that reduce socioeconomic disparities and allow us to reach the levels of health and life expectancy achieved in peer societies. PMID- 26561274 TI - Unmet need for treatment of depression among immigrants from the former USSR in the US: A primary care study. AB - The stress of immigration can increase risk for major depressive disorder (MDD), while cultural factors can contribute to difficulty in diagnosis and treatment of MDD among immigrant populations. Consequently, immigrants are less likely to have their treatment needs met. Our goal was to assess the unmet need for the diagnosis and treatment of depression among immigrants from the former USSR-a large immigrant group in the US-as well as demographic characteristics and immigration history associated with depression. We conducted a survey in an urban primary care clinic using measures of MDD symptoms (Patient Health Questionnaire 9), functioning, and treatment history among 102 Russian-speaking immigrants. Current moderate-to-severe symptoms of MDD were reported by 26.5% of participants with 33.3% of the symptomatic patients reporting suicidal ideation. Among participants with probable MDD, 63.0% reported not receiving mental health treatment and 59.3% never being diagnosed with MDD. The rates of untreated depression did not vary by gender nor did they diminish with prolonged stay in the US. Results suggest that undiagnosed and untreated depression is highly prevalent in this immigrant group. PMID- 26561275 TI - Traumatic experiences, posttraumatic stress symptoms, depression, and health-risk behavior in relation to injury among University of Nairobi students in Kenya. AB - OBJECTIVE: To describe the prevalence and types of injuries in relation to traumatic experiences, posttraumatic stress symptoms, depression, and health-risk behaviors among university students in Kenya. METHOD: A cross-sectional study collected data on a random sample of university students using a questionnaire to record sociodemographic variables while injuries experiences recorded using the Centers for Disease control criteria and Breslau's seven-item screener was used to identify post-traumatic stress disorder (PTSD) symptoms. Depressive symptoms were measured using Center for Epidemiological Studies Short Depression Scale. RESULTS: Nine hundred and twenty-three students (525 male and 365 female) were included in the study, mean age 23 years (SD 4.0). Serious injury in the previous 12 months was reported by 29.00% of the students. PTSD was present in 15.67% (men 15.39% and women 16.1%). Out of the total, 41.33% of the students had depressive symptoms (35.71% mild-moderate symptoms and 5.62% severe). In the multivariable logistic regression being poor, binge drinking, tobacco use, ever been diagnosed with HIV, physically abused as a child, high PTSD score, and depression (adjusted odds ratio 5.49, 95% confidence interval 4.32-13.21) were significantly (p value<5%) associated with injury in the last 12 months. CONCLUSION: Unintentional injuries and PTSD symptoms are common in this student population and are positively linked to depression and other risky behaviors. Measures aimed at improving the mental health, such as early identification and treatment of depression, may be useful in reducing the prevalence of such injuries among the youth. PMID- 26561276 TI - Comparison of dose and catheter optimization algorithms in prostate high-dose rate brachytherapy. AB - PURPOSE: The purpose of this work was to compare the hybrid inverse treatment planning optimization (HIPO), inverse dose-volume histogram-based optimization (DVHO), and fast simulated annealing stochastic algorithm (IPSA). The catheter optimization algorithm HIPO was also compared with the Centroidal Voronoi Tessellation (CVT) algorithm. METHODS AND MATERIALS: In this study, eight high dose-rate prostate cases were randomly selected from an anonymized bank of patients. Oncentra Prostate v4.1 was used to run DVHO and the HIPO catheter optimization (HIPO_cat), whereas Oncentra Brachy v4.3 was used for the remaining. For fixed catheter configurations, DVHO plans were compared with IPSA and HIPO. For catheter positions optimization, CVT and HIPO_cat algorithms were compared with standard clinical template plans. CVT catheters were further restrained to the template grid (CVT_grid) and compared with HIPO_cat. RESULTS: For dose optimization, IPSA and HIPO were not different from each other. The urethra D10 and the computation time were found significantly better with IPSA and HIPO compared with DVHO (p < 0.0001). All other dosimetric indices were not statistically different from each others (p > 0.05). For catheter placement, CVT plans were better, whereas HIPO_cat plans were significantly worse (p < 0.05) than standard clinical plans. CVT_grid plans were similar to clinical plans and fulfilling American Brachytherapy Society guidelines down to 12 catheters, whereas HIPO_cat plans do not for all catheter numbers. The CVT algorithm run time was significantly faster than HIPO_cat (p < 0.0001). CONCLUSIONS: Dose optimization engines IPSA, DVHO, and HIPO give similar dosimetric results. The CVT approach was found to be better than HIPO_cat and was able to reduce the number of catheters significantly. PMID- 26561278 TI - Retraction of "Fabrication of Tantalum and Nitrogen Codoped ZnO (Ta, N-ZnO) Thin Films Using the Electrospay: Twin Applications as an Excellent Transparent Electrode and a Field Emitter". PMID- 26561277 TI - American Brachytherapy Society consensus guidelines for thoracic brachytherapy for lung cancer. AB - PURPOSE: To update brachytherapy recommendations for pretreatment evaluation, treatment, and dosimetric issues for thoracic brachytherapy for lung cancer. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in thoracic brachytherapy updated recommendations for thoracic brachytherapy based on literature review and clinical experience. RESULTS: The American Brachytherapy Society consensus guidelines recommend the use of endobronchial brachytherapy for disease palliation in patients with central obstructing lesions, particularly in patients who have previously received external beam radiotherapy. The use of interstitial implants after incomplete resection may improve outcomes and provide enhanced palliation. Early reports support the use of CT-guided intratumoral volume implants within clinical studies. The use of brachytherapy routinely after sublobar resection is not generally recommended, unless within the confines of a clinical trial or a registry. CONCLUSIONS: American Brachytherapy Society recommendations for thoracic brachytherapy are provided. Practitioners are encouraged to follow these guidelines and to develop further clinical trials to examine this treatment modality to increase the evidence base for its use. PMID- 26561279 TI - Ambient Mass Spectrometry Imaging with Picosecond Infrared Laser Ablation Electrospray Ionization (PIR-LAESI). AB - A picosecond infrared laser (PIRL) is capable of cutting through biological tissues in the absence of significant thermal damage. As such, PIRL is a standalone surgical scalpel with the added bonus of minimal postoperative scar tissue formation. In this work, a tandem of PIRL ablation with electrospray ionization (PIR-LAESI) mass spectrometry is demonstrated and characterized for tissue molecular imaging, with a limit of detection in the range of 100 nM for reserpine or better than 5 nM for verapamil in aqueous solution. We characterized PIRL crater size using agar films containing Rhodamine. PIR-LAESI offers a 20-30 MUm vertical resolution (~3 MUm removal per pulse) and a lateral resolution of ~100 MUm. We were able to detect 25 fmol of Rhodamine in agar ablation experiments. PIR-LAESI was used to map the distribution of endogenous methoxykaempferol glucoronide in zebra plant (Aphelandra squarrosa) leaves producing a localization map that is corroborated by the literature. PIR-LAESI was further used to image the distribution inside mouse kidneys of gadoteridol, an exogenous magnetic resonance contrast agent intravenously injected. Parallel mass spectrometry imaging (MSI) using desorption electrospray ionization (DESI) and matrix assisted laser desorption ionization (MALDI) were performed to corroborate PIR-LAESI images of the exogenous agent. We further show that PIR LAESI is capable of desorption ionization of proteins as well as phospholipids. This comparative study illustrates that PIR-LAESI is an ion source for ambient mass spectrometry applications. As such, a future PIRL scalpel combined with secondary ionization such as ESI and mass spectrometry has the potential to provide molecular feedback to guide PIRL surgery. PMID- 26561280 TI - Factors Associated with Hepatitis C Knowledge Before and After an Educational Intervention among Vietnamese Americans. AB - BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease and cancer. Vietnamese Americans are at high risk of HCV infection, with men having the highest US incidence of liver cancer. This study examines an intervention to improve HCV knowledge among Vietnamese Americans. STUDY: Seven Vietnamese community-based organizations in Pennsylvania and New Jersey recruited a total of 306 Vietnamese participants from 2010 to 2011. RESULTS: Average knowledge scores for pretest and posttest were 3.32 and 5.88, respectively (maximum 10). After adjusting for confounding variables, age and higher education were positively associated with higher pretest scores and having a physician who spoke English or Vietnamese was negatively associated with higher pretest scores. Additionally, after adjusting for confounding variables, household income, education, and having an HCV-infected family member significantly increased knowledge scores. CONCLUSIONS: Promotion and development of HCV educational programs can increase HCV knowledge among race and ethnic groups, such as Vietnamese Americans. Giving timely information to at-risk groups provides the opportunity to correct misconceptions, decrease HCV risk behaviors, and encourage testing that might improve timely HCV diagnosis and treatment. PMID- 26561281 TI - A wearable wound moisture sensor as an indicator for wound dressing change: an observational study of wound moisture and status. AB - Wound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large-scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44.9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed. PMID- 26561282 TI - Platelet-rich plasma for bone healing and regeneration. AB - INTRODUCTION: Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. AREAS COVERED: Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. EXPERT OPINION: As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP. PMID- 26561283 TI - First Robotic SPECT for Minimally Invasive Sentinel Lymph Node Mapping. AB - In this paper we present the usage of a drop-in gamma probe for intra-operative Single-Photon Emission Computed Tomography (SPECT) imaging in the scope of minimally invasive robot-assisted interventions. The probe is designed to be inserted and reside inside the abdominal cavity during the intervention. It is grasped during the procedure using a robotic laparoscopic gripper enabling full six degrees of freedom handling by the surgeon. We demonstrate the first deployment of the tracked probe for intra-operative in-patient robotic SPECT enabling augmented-reality image guidance. The hybrid mechanical- and image-based in-patient probe tracking is shown to have an accuracy of 0.2 mm. The overall system performance is evaluated and tested with a phantom for gynecological sentinel lymph node interventions and compared to ground-truth data yielding a mean reconstruction accuracy of 0.67 mm. PMID- 26561284 TI - Extracting Information From Previous Full-Dose CT Scan for Knowledge-Based Bayesian Reconstruction of Current Low-Dose CT Images. AB - Markov random field (MRF) model has been widely employed in edge-preserving regional noise smoothing penalty to reconstruct piece-wise smooth images in the presence of noise, such as in low-dose computed tomography (LdCT). While it preserves edge sharpness, its regional smoothing may sacrifice tissue image textures, which have been recognized as useful imaging biomarkers, and thus it may compromise clinical tasks such as differentiating malignant vs. benign lesions, e.g., lung nodules or colon polyps. This study aims to shift the edge preserving regional noise smoothing paradigm to texture-preserving framework for LdCT image reconstruction while retaining the advantage of MRF's neighborhood system on edge preservation. Specifically, we adapted the MRF model to incorporate the image textures of muscle, fat, bone, lung, etc. from previous full-dose CT (FdCT) scan as a priori knowledge for texture-preserving Bayesian reconstruction of current LdCT images. To show the feasibility of the proposed reconstruction framework, experiments using clinical patient scans were conducted. The experimental outcomes showed a dramatic gain by the a priori knowledge for LdCT image reconstruction using the commonly-used Haralick texture measures. Thus, it is conjectured that the texture-preserving LdCT reconstruction has advantages over the edge-preserving regional smoothing paradigm for texture specific clinical applications. PMID- 26561285 TI - Furospinosulin-1, Marine Spongean Furanosesterterpene, Suppresses the Growth of Hypoxia-Adapted Cancer Cells by Binding to Transcriptional Regulators p54(nrb) and LEDGF/p75. AB - Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. Cancer research has therefore focused on the identification of molecules responsible for hypoxia adaptation in cancer cells, as well as the development of new compounds with action against hypoxia-adapted cancer cells. The marine natural product furospinosulin-1 (1) has displayed hypoxia-selective growth inhibition against cultured cancer cells, and has shown in vivo anti-tumor activity, although its precise mode of action and molecular targets remain unclear. In this study, we found that 1 is selectively effective against hypoxic regions of tumors, and that it directly binds to the transcriptional regulators p54(nrb) and LEDGF/p75, which have not been previously identified as mediators of hypoxia adaptation in cancer cells. PMID- 26561286 TI - Early radiosurgery provides superior pain relief for trigeminal neuralgia patients. AB - OBJECTIVE: We evaluated factors associated with better outcomes after stereotactic radiosurgery (SRS) when it was performed as the first surgical procedure for medically refractory trigeminal neuralgia. METHODS: A total of 121 patients (median age 72 years) with medically refractory pain and no prior surgery underwent Gamma Knife SRS as their initial surgical procedure for trigeminal neuralgia. Using a single 4-mm isocenter, patients received an average maximum dose of 80 Gy, delivered to the trigeminal nerve target defined by intraoperative MRI. The median follow-up was 36 months. RESULTS: Pain relief (Barrow Neurological Institute [BNI] score I-IIIa) was achieved in 107 (88%) patients at a median time of 1 month. Patients who underwent earlier SRS (within 3 years of pain onset) had a shorter interval until pain relief (1 week, p < 0.001), had a longer interval of pain relief off medication (BNI-I, p < 0.001), and had a longer duration of adequate pain control (BNI-I-IIIa, p < 0.001). Median pain-free intervals for patients who underwent SRS at 1, 2, 3, and more than 3 years after trigeminal neuralgia diagnosis were 68, 37, 36, and 10 months, respectively. Patients who responded to SRS within the first 3 weeks after SRS had a longer duration of complete pain relief compared to those with longer response times (p = 0.001). Fifteen patients (12%) reported new sensory dysfunction after SRS. CONCLUSION: Early SRS as the initial surgical procedure for management of refractory trigeminal neuralgia was associated with faster, better, and longer pain relief when compared to late SRS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with medically refractory trigeminal neuralgia, early stereotactic radiosurgery as the initial procedure provides faster, better, and longer pain relief. PMID- 26561287 TI - Cerebral injury in perinatally HIV-infected children compared to matched healthy controls. AB - OBJECTIVE: The current study aims to evaluate the neurologic state of perinatally HIV-infected children on combination antiretroviral therapy and to attain a better insight into the pathogenesis of their persistent neurologic and cognitive deficits. METHODS: We included perinatally HIV-infected children between 8 and 18 years and healthy controls matched for age, sex, ethnicity, and socioeconomic status. All participants underwent a 3.0 T MRI with 3D-T1-weighted, 3D-fluid attenuated inversion recovery, and diffusion-weighted series for the evaluation of cerebral volumes, white matter hyperintensities (WMH), and white matter (WM) diffusion characteristics. Associations with disease-related parameters and cognitive performance were explored using linear regression models. RESULTS: We included 35 cases (median age 13.8 years) and 37 controls (median age 12.1 years). A lower gray matter and WM volume, more WMH, and a higher WM diffusivity were observed in the cases. Within the HIV-infected children, a poorer clinical, immunologic, and virologic state were negatively associated with volumetric, WMH, and diffusivity markers. CONCLUSIONS: In children with HIV, even when long-term clinically and virologically controlled, we found lower brain volumes, a higher WMH load, and poorer WM integrity compared to matched controls. These differences occur in the context of a poor cognitive performance in the HIV-infected group, and larger, longitudinal studies are needed to increase our understanding of the pathogenesis of cerebral injury in perinatally HIV-infected children. PMID- 26561288 TI - Tilt-induced vasovagal syncope and psychogenic pseudosyncope: Overlapping clinical entities. AB - OBJECTIVE: To describe the combination of tilt-induced vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) and aid its clinical recognition. METHODS: We identified people with tilt-induced VVS/PPS from 2 tertiary syncope referral centers. For each case, 3 controls with tilt-induced VVS were selected at random from the same center. Clinical characteristics were compared between both groups adjusting for multiple comparisons. RESULTS: Of 1,164 tilt-table tests, 23 (2%) resulted in VVS/PPS; these 23 cases were compared with 69 VVS controls. VVS and PPS coincided more often than chance would predict: 2% vs 0.6%, p < 0.001. Typical VVS prodromes and triggers were reported in all people with VVS/PPS and in controls with VVS. Attack frequency was significantly higher in the VVS/PPS (2 per month, range 0.1-60) than in the VVS group (0.25 per month, range 0.02-4; p < 0.001). Delayed recovery of consciousness was more frequently reported in the VVS/PPS group (likelihood ratio [+LR] 8.14, 95% confidence interval [CI] 3.94 16.84), as well as episodes without prodromes (+LR 5.57, 95% CI 2.53-12.26), atypical triggers (+LR 5.00, 95% CI 2.04-12.24), eye closure (+LR 3.75, 95% CI 1.68-8.35), and apparent loss of consciousness >1 minute (+LR 2.86, 95% CI 1.98 4.13). CONCLUSIONS: VVS/PPS presents with a complex phenotype. High attack frequency, delayed recovery of consciousness, apparent loss of consciousness >1 minute, ictal eye closure, atypical triggers, and the absence of prodromes may serve as indicators that PPS coincides with VVS. PMID- 26561289 TI - Milder phenotype in facioscapulohumeral dystrophy with 7-10 residual D4Z4 repeats. AB - OBJECTIVE: To examine the relationship of clinical and genetic features of patients with facioscapulohumeral muscular dystrophy (FSHD) with 7-10 residual D4Z4 repeats in a large genetically defined FSHD1 cohort. METHODS: We performed a prospective cross-sectional observational study of 74 clinically affected patients with FSHD1. Measures of clinical severity were compared between patients with 1-6 D4Z4 repeats and 7-10 repeats, and included D4Z4 CpG methylation, age at diagnosis, age-adjusted clinical severity score, a muscle pathology grade of quadriceps biopsies (0 = normal, 12 = severe dystrophic changes), quantitative myometry of biopsied muscles, global manual muscle testing scores, and frequency of wheelchair use. RESULTS: Twenty-eight (37.8%) participants had 7-10 D4Z4 repeats, and compared to participants with 1-6 repeats, were diagnosed 6.6 years older (p = 0.17); had lower CpG methylation than would be predicted by D4Z4 repeat size (p = 0.04); had age-adjusted clinical severity 39.8 points lower (p = 0.004); had muscle pathology grades that were 2.4 points less severe (p < 0.0001); had quantitative myometry 28.3% predicted of normal higher (p = 0.002); had global manual muscle testing scores 0.6 higher (p = 0.005); and did not require wheelchairs. CONCLUSION: Patients with FSHD with 7-10 D4Z4 repeats have milder disease than other genetically defined patients with FSHD1. The lower than predicted methylation in the 7-10 residual repeat group may suggest that additional epigenetic factors play a role in the severity of disease expression. PMID- 26561291 TI - Psychogenic symptoms are not only for the epileptologist: All physicians be aware! PMID- 26561292 TI - Perinatal HIV in the brain: Mission incomplete despite combination antiretroviral therapy. PMID- 26561290 TI - Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. AB - OBJECTIVE: To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations. METHODS: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls). Immunohistochemistry and immunofluorescence studies were performed on pathologic LBD cases with rare CHCHD2 variants. RESULTS: We identified 9 rare exonic variants of unknown significance. These variants were more frequent in the combined group of PD and LBD patients compared to controls (0.6% vs 0.1%, p = 0.013). In addition, the presence of any rare variant was more common in patients with LBD (2.5% vs 1.0%, p = 0.050) compared to controls. Eight of these 9 variants were located within the gene's mitochondrial targeting sequence. CONCLUSIONS: Although the role of variants of the CHCHD2 gene in PD and LBD remains to be further elucidated, the rare variants in the mitochondrial targeting sequence may be a risk factor for Lewy body disorders, which may link CHCHD2 to other genetic forms of parkinsonism with mitochondrial dysfunction. PMID- 26561293 TI - Is more really better? The effect of enrollment volume on outcomes for medical therapies. PMID- 26561295 TI - Rare genetic variants support mitochondrial dysfunction in Lewy body disorders. PMID- 26561294 TI - Enrollment volume effect on risk factor control and outcomes in the SAMMPRIS trial. AB - OBJECTIVE: The role of physician experience and patient volumes on the outcome of surgical or endovascular procedures has been well-studied but there are limited data on how these factors affect the outcome of medical therapy. METHODS: In the stenting and medical cohorts of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial, we compared Kaplan-Meier (K-M) curves for the primary endpoint (any stroke or death within 30 days of enrollment or ischemic stroke in the territory beyond 30 days) using the log-rank test and the percentages of patients achieving target levels for primary and secondary risk factors during the study using Fisher exact test between patients at high-enrolling (>=12 patients) vs low-enrolling (<12 patients) sites. RESULTS: In the stenting group, the K-M curves for the primary endpoint were similar at high-enrolling sites and low-enrolling sites (p = 0.93) with rates of 13.5% vs 14.7% at 30 days and 19.0% vs 20.6% at 2 years. In the medical group, the K-M curves differed between high-enrolling sites and low-enrolling sites (p = 0.0005) with rates of 1.8% vs 9.8% at 30 days and 7.3% vs 20.9% at 2 years. The percentages of patients who achieved targets for low-density lipoprotein cholesterol and systolic blood pressure at high- vs low-enrolling sites in both treatment groups combined were 64% vs 49% (p = 0.003) and 70% vs 59% (p = 0.026), respectively. CONCLUSIONS: High-enrolling sites in SAMMPRIS achieved better control of primary risk factors and much lower rates of the primary endpoint than low-enrolling sites in the medical group, suggesting that experience with medical management is an important determinant of patient outcome. PMID- 26561296 TI - Disruption of posteromedial large-scale neural communication predicts recovery from coma. AB - OBJECTIVE: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks. METHODS: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 +/- 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest-based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale-Revised (CRS-R). RESULTS: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman rho = 0.93, p < 0.003). CONCLUSION: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker. PMID- 26561297 TI - MYC-induced reprogramming of glutamine catabolism supports optimal virus replication. AB - Viruses rewire host cell glucose and glutamine metabolism to meet the bioenergetic and biosynthetic demands of viral propagation. However, the mechanism by which viruses reprogram glutamine metabolism and the metabolic fate of glutamine during adenovirus infection have remained elusive. Here, we show MYC activation is necessary for adenovirus-induced upregulation of host cell glutamine utilization and increased expression of glutamine transporters and glutamine catabolism enzymes. Adenovirus-induced MYC activation promotes increased glutamine uptake, increased use of glutamine in reductive carboxylation and increased use of glutamine in generating hexosamine pathway intermediates and specific amino acids. We identify glutaminase (GLS) as a critical enzyme for optimal adenovirus replication and demonstrate that GLS inhibition decreases replication of adenovirus, herpes simplex virus 1 and influenza A in cultured primary cells. Our findings show that adenovirus-induced reprogramming of glutamine metabolism through MYC activation promotes optimal progeny virion generation, and suggest that GLS inhibitors may be useful therapeutically to reduce replication of diverse viruses. PMID- 26561298 TI - Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis. AB - BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA) plus simvastatin (SS) with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism. MATERIALS AND METHODS: The experimental Sprague-Dawley rats were divided randomly into normal control (control), sham operated (sham), ARDS, ARDS + vehicle and ARDS + RA + SS groups. ARDS was reproduced through hemorrhagic shock/resuscitation (shock) and subsequent intratracheal LPS (4.5 mg/kg, Escherichia coli serotype O55: B5) injection. The rats were treated by intragastric administration of RA (2 mg/kg/day) and SS (2 mg/kg/day) for 5 days in the ARDS + RA + SS group. Seven days after the first RA SS injection, a right lower lobe of lung was sampled for histological analysis concerning systemic uniform random sampling method. Immunohistochemistry of inflation-fixed lungs for alveolar type 1 (AT1), alveolar type 2 (AT2) and Clara cells was measured by AQP5, Pro-SPC and CCSP staining respectively. The alveolar cell proliferation and apoptosis were analyzed with Ki67 staining and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. Meanwhile, the alveolar cell numerical and surface density (alveolar cells, AT1, AT2, Clara, proliferating and apoptotic cells) were evaluated by stereology. RESULTS: RA-SS compound exerted anti-inflammatory and pro-repairing effects on respiratory tracts in ARDS induced by hemorrhagic-endotoxin shock. The numerical density and surface density of alveolar cells, AT1 cell fraction, and numerical density of AT2 and Clara cells were significantly increased after treatment with RA-SS compound in ARDS. Concurrently, the Ki67+ alveolar cells were obviously increased while the TUNEL+ alveolar cells were reduced, which was correlated with the attenuation of inflammatory injury and functional repair in injured lung tissues. CONCLUSIONS: Our data convincingly indicated that the prophylactic and therapeutic treatment of RA plus SS had obvious beneficial effect on the remodeling/regeneration of injured pulmonary tissues, suggesting that the underlying mechanisms are related to the re-balance between regeneration and apoptosis in lung stem/progenitor cells. PMID- 26561299 TI - Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses. AB - Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied. PMID- 26561300 TI - Predictors of the development of post-snakebite compartment syndrome. AB - BACKGROUND: To identify the factors associated with the development of post snakebite compartment syndrome (PSCS) in snakebite patients and to analyze the clinical prognosis of these patients. METHODS: We retrospectively reviewed the medical records of patients who presented to our institution with snakebites from March 2009 to December 2012. The clinical data, hospital course and outcome were all recorded. RESULTS: A total of 136 patients were included in the present study. Nine patients developed PSCS and underwent fasciotomy. Relative to the non PSCS group, the PSCS group demonstrated a significant increase in the white blood cell count (WBC, p = 0.006), segment form (Seg, p <= 0.001), aspartate aminotransferase level (AST, p = 0.002) and alanine aminotransferase level (ALT, p = 0.008). Elevated WBC count and AST level were identified as independent risk factors for PSCS (p = 0.028 and 0.037, respectively) in a multivariate analysis. CONCLUSIONS: Snakebite patients have a high likelihood of developing locoregional complications such as PSCS. Symptomatic snakebite patients should be observed for at least 48 h, and increased WBC counts and AST levels are risk factors for PSCS. PMID- 26561301 TI - The effects of different lipid emulsions on the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants: A double-blind, randomized clinical trial. AB - BACKGROUND & AIMS: Olive oil (OO), medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture and soybean oil (SO) lipid emulsions are currently used for preterm infants in China. The aim of our study was to compare the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants administered OO, MCT/LCT, or SO lipid emulsions. METHODS: In this study, 156 preterm infants (birth weight < 2000 g and gestational age < 37 weeks) received parenteral nutrition (PN) containing OO, MCT/LCT, or SO lipid emulsions for a minimum of 14 d. On days 0, 7, and 14, the lipid profile, fatty acid composition and antioxidant capacity were analyzed. RESULTS: On day 7, HDL levels in the MCT/LCT group were significantly lower than in the OO (1.06 +/- 0.40 mmol/L) or SO groups. LDL levels were higher in the OO group than in the MCT/LCT or SO groups on day 7. A-I/B was higher in MCT/LCT than in OO or SO groups. Myristic acid (C14:0) levels on days 7 and 14 increased in MCT/LCT compared to the OO and SO groups. The OO group had higher oleic acid (C18:1n9) levels than the two other groups. Linoleic acid (C18:2n6), linolenic acid (C18:3n3), and eicosapentaenoic acid (20:5n3) were significantly lower in the OO group than in MCT/LCT or SO groups. Monounsaturated fatty acid levels decreased, and omega-6 polyunsaturated fatty acid and essential fatty acids levels increased in MCT/LCT and SO groups. No significant differences were obtained in SOD, MDA, GSH-Px, and T-AOC among the groups. CONCLUSION: The three lipid emulsions were safe and well tolerated in preterm infants. Oleic acid (C18:1n9) levels increased and LA (C18:2n6), ALA (C18:3n3), and EPA (C20:5n23) levels decreased in OO compared to MCT/LCT or SO. CLINICAL TRIAL REGISTRATION NUMBER: NCT01683162, https://register.clinicaltrials.gov/. PMID- 26561302 TI - A Non-Invasive Droplet Digital PCR (ddPCR) Assay to Detect Paternal CFTR Mutations in the Cell-Free Fetal DNA (cffDNA) of Three Pregnancies at Risk of Cystic Fibrosis via Compound Heterozygosity. AB - INTRODUCTION: Non-invasive prenatal diagnosis (NIPD) makes use of cell-free fetal DNA (cffDNA) in the mother's bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a 0.5-1% risk of fetal loss. We describe a droplet digital PCR (ddPCR) assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in the cffDNA, it is possible to predict whether the fetus will be an unaffected carrier (absence) or whether further invasive testing is indicated (presence). METHODS: We selected a family in which the parents were known to carry different mutated CFTR alleles as our test system. NIPD was performed for three of their pregnancies during the first trimester (at around 11-12 weeks of gestation). Taqman probes were designed against an amplicon in exon 11 of the CFTR gene, to quantify the proportion of mutant (DeltaF508-MUT; FAM) and normal (DeltaF508-NOR; VIC) alleles at position c.1521_1523 of the CFTR gene. DISCUSSION: The assay correctly and unambiguously recognized the DeltaF508-MUT CFTR allele in the cffDNA of all three proband fetuses and none of the six unaffected control fetuses. In conclusion, the Bio-Rad QX100 was found to be a cost-effective and technically undemanding platform for designing bespoke NIPD assays. PMID- 26561304 TI - Optimizing the diagnosis and the treatment of iron overload diseases. AB - A number of human disorders are related to chronic iron overload, either of genetic or acquired origin. The multi-organ damage produced by iron excess leads, in adults and in children, to severe clinical consequences, affecting both quality of life and life expectancy. The diagnosis is increasingly based on a non invasive strategy, resorting to clinical, biological and imaging data. The treatment rests on either venesection or chelation therapy, depending on the etiology. Major advances in the fields of molecular biology, pharmacology, and biotechnology pave the road for key improvements in the diagnostic and therapeutic management of the patients. PMID- 26561303 TI - Correlated expression of retrocopies and parental genes in zebrafish. AB - Previous studies of the function and evolution of retrocopies in plants, Drosophila and non-mammalian chordates provided new insights into the origin of novel genes. However, little is known about retrocopies and their parental genes in teleosts, and it remains obscure whether there is any correlation between them. The present study aimed to characterize the spatial and temporal expression profiles of retrogenes and their parental genes based on RNA-Seq data from Danio rerio embryos and tissues from adult. Using a modified pipeline, 306 retrocopies were identified in the zebrafish genome, most of which exhibited ancient retroposition, and 76 of these showed a Ks < 2.0. Expression of a retrocopy is generally expected to present no correlation with its parental gene, as regulatory regions are not part of the retroposition event. Here, this assumption was tested based on RNA-Seq data from eight stages and thirteen tissue types of zebrafish. However, the result suggested that retrocopies displayed correlated expression with their parental genes. The level of correlation was found to decrease during embryogenesis, but to increase slightly within a tissue using Ks as the proxy for the divergence time. Tissue specificity was also observed: retrocopies were found to be expressed at a more specific level compared with their parental genes. Unlike Drosophila, which has sex chromosomes, zebrafish do not show testis-biased expression. Our study elaborated temporal and spatial patterns of expression of retrocopies in zebrafish, examined the correlation between retrocopies and parental genes and analyzed potential source of regulated elements of retrocopies, which lay a foundation for further functional study of retrocopies. PMID- 26561305 TI - Effects of Propofol on Excitatory and Inhibitory Amino Acid Neurotransmitter Balance in Rats with Neurogenic Pulmonary Edema Induced by Subarachnoid Hemorrhage. AB - INTRODUCTION: Propofol exhibits neuroprotective effects mediated by the inhibition of excitatory amino acid (EAA) neurotransmitter release and potentiation of inhibitory amino acid (IAA) neurotransmitters. To our knowledge, this is the first study to investigate the effects of propofol on the EAA and IAA balance in neurogenic pulmonary edema (NPE). METHODS: Sixty male Wistar rats were randomized to Sham, NPE, Low-dose propofol, and High-dose propofol groups. NPE was induced via rapid injection of autologous blood (0.5 ml) into the cisterna magna. The Low- and High-dose propofol groups were pretreated with boluses of 2 and 5 mg kg(-1), respectively, prior to blood injection, followed by continuous propofol infusion at 6 and 15 mg kg(-1) h(-1), respectively. The mean arterial pressure (MAP), heart rate, intracranial pressure (ICP), peak inspiratory pressure (PIP), and arterial blood gases were continuously recorded. After 2 h, the lung wet-to-dry weight ratio, total protein concentration in the bronchoalveolar lavage fluid (BALF), brain water content, cortical EAA and IAA levels, chest X-ray, and histological staining of lung sections were evaluated. RESULTS: Blood injections into the cisterna magna induced NPE and hemodynamic changes. Propofol alleviated the increases in the MAP, ICP, and PIP, improved oxygenation and histopathological changes, ameliorated pulmonary and cerebral edema, increased the IAA brain levels, and decreased the ratio of Glu to gamma aminobutyric acid. CONCLUSIONS: The current findings suggest that propofol improves NPE likely via IAA accumulation and the regulation of EAA and IAA balance, which may represent an effective treatment for NPE. PMID- 26561306 TI - Multiple-trait- and selection indices-genomic predictions for grain yield and protein content in rye for feeding purposes. AB - KEY MESSAGE: Exploiting the benefits from multiple-trait genomic selection for protein content prediction relying on additional grain yield information within training sets is a realistic genomic selection approach in rye breeding. ABSTRACT: Multiple-trait genomic selection (MTGS) was specially designed to benefit from the information of genetically correlated indicator traits in order to improve genomic prediction accuracies. Two segregating F3:4 rye testcross populations genotyped using diversity array technology markers and evaluated for grain yield (GY) and protein content (PC) were considered. The aims of our study were to explore the benefits of MTGS over single-trait genomic selection (STGS) for GY and PC prediction and to apply GS to predict different selection indices (SIs) for GY and PC improvement. Our results using a two-trait model (2TGS) empirically confirm that the ideal scenario to exploit the benefits of MTGS would be when the predictions of a relatively low heritable target trait with scarce phenotypic records are supported by an intensively phenotyped genetically correlated indicator trait which has higher heritability. This ideal scenario is expected for PC in practice. According to our GS implementation, MTGS can be performed in order to achieve more cycles of selection by unit of time. If the aim is to exclusively improve the prediction accuracy of a scarcely phenotyped trait, 2TGS will be a more accurate approach than a three-trait model which incorporates an additional correlated indicator trait. In general for balanced phenotypic information, we recommend to perform GS considering SIs as single traits, this method being a simple, direct and efficient way of prediction. PMID- 26561307 TI - Pre-Historic and Recent Vicariance Events Shape Genetic Structure and Diversity in Endangered Lion-Tailed Macaque in the Western Ghats: Implications for Conservation. AB - Genetic isolation of populations is a potent force that helps shape the course of evolution. However, small populations in isolation, especially in fragmented landscapes, are known to lose genetic variability, suffer from inbreeding depression and become genetically differentiated among themselves. In this study, we assessed the genetic diversity of lion-tailed macaques (Macaca silenus) inhabiting the fragmented landscape of Anamalai hills and examined the genetic structure of the species across its distributional range in the Western Ghats. We sequenced around 900 bases of DNA covering two mitochondrial regions hypervariable region-I and partial mitochondrial cytochrome b-from individuals sampled both from wild and captivity, constructed and dated phylogenetic trees. We found that the lion-tailed macaque troops in the isolated forest patches in Anamalai hills have depleted mitochondrial DNA diversity compared to troops in larger and continuous forests. Our results also revealed an ancient divergence in the lion-tailed macaque into two distinct populations across the Palghat gap, dating to 2.11 million years ago. In light of our findings, we make a few suggestions on the management of wild and captive populations. PMID- 26561308 TI - Mindfulness in people with a respiratory diagnosis: A systematic review. AB - OBJECTIVES: To describe how mindfulness is delivered and to examine the effect of mindfulness on health-related quality of life (HRQOL), mindful awareness and stress in adults with a respiratory diagnosis. METHOD: Five electronic databases were searched. Data were extracted and assessed for quality by two reviewers. RESULTS: Data were extracted from four studies. Interventions were based on Mindfulness-Based Stress Reduction and delivered by trained instructors. Recordings of mindfulness were provided for home-based practice. One study targeted the intervention exclusively to anxious individuals with a respiratory diagnosis. Adherence to mindfulness was poor. No effects were seen on disease specific HRQOL (standardized mean difference (SMD)=-0.21 95% CI: -0.36 to 0.48, p=0.78), mindful awareness (SMD=0.09 95% CI: -0.34 to 0.52, p=0.68) or stress levels (SMD =-0.11 95% CI: -0.46 to 0.23, p=0.51). CONCLUSION: Mindfulness interventions, delivered to individuals with a respiratory diagnosis, varied widely in terms of delivery and the outcomes assessed making it difficult to draw any conclusions regarding its effectiveness. PMID- 26561309 TI - A microanalysis of the clarity of information in physicians' and patients' discussions of treatment plans with and without language barriers. AB - OBJECTIVE: Physicians and patients discuss treatment plans. If tasks within plans are not described adequately, patients cannot adhere. We evaluated task descriptions, testing whether patient engagement and language barriers affected task clarity. METHOD: We sampled 12 videotaped hospital interactions from a corpus of 497: two encounters each from six hospital physicians, interacting with one native-speaking and one non-native-speaking patient. We used microanalysis of face-to-face dialogue to assess whether the physicians and patients achieved a complete, clear description of each task's three core information elements (who should do what and when). RESULTS: We conducted detailed analysis on 78 of the 90 tasks. Core information elements were complete in 62 (0.79) and clear in 37 (0.47). Language barriers had no effect on task clarity. When native-speaking patients were engaged, tasks were clearer (p<0.05). Although non-native-speaking patients were significantly more engaged (p<0.01), their engagement had no effect. CONCLUSION: Physicians may be pursuing patients' agreement, motivation, and commitment at the expense of working with the patient to be clear about what needs to be done. PRACTICE IMPLICATIONS: Physicians need to improve how clearly they present basic task information. Previous research demonstrated that even a short course can significantly improve the clarity of instructions. PMID- 26561310 TI - Death talk: Basic linguistic rules and communication in perinatal and paediatric end-of-life discussions. AB - OBJECTIVE: This paper considers clinician/parent communication difficulties noted by parents involved in end-of-life decision-making in the light of linguistic theory. METHODS: Grice's Cooperative Principle and associated maxims, which enable effective communication, are examined in relation to communication deficiencies that parents have identified when making end-of-life decisions for the child. Examples from the literature are provided to clarify the impact of failing to observe the maxims on parents and on clinician/parent communication. RESULTS: Linguistic theory applied to the literature on parental concerns about clinician/parent communication shows that the violation of the maxims of quantity, quality, relation, and manner as well as the stance that some clinicians adopt during discussions with parents impact on clinician/parent communication and lead to distrust, anger, sadness, and long-term difficulties coping with the experience of losing one's child. CONCLUSION: Parents have identified communication deficiencies in end-of-life discussions. Relating these communication deficiencies to linguistic theory provides insight into communication difficulties but also solutions. PRACTICE IMPLICATIONS: Gaining an understanding of basic linguistic theory that underlies human interactions, gaining insight into the communication deficiencies that parents have identified, and modifying some communication behaviours in light of these with the suggestions made in this article may lead to improved clinician/parent communication. PMID- 26561311 TI - Determinants of intention to change health-related behavior and actual change in patients with TIA or minor ischemic stroke. AB - OBJECTIVE: To assess determinants of intention to change health-related behavior and actual change in patients with TIA or ischemic stroke. METHODS: In this prospective cohort study, 100 patients with TIA or minor ischemic stroke completed questionnaires on behavioral intention and sociocognitive factors including perception of severity, susceptibility, fear, response-efficacy and self-efficacy at baseline. Questionnaires on physical activity, diet and smoking were completed at baseline and at 3 months. Associations between sociocognitive factors and behavioral intention and actual change were studied with multivariable linear and logistic regression. RESULTS: Self-efficacy, response efficacy, and fear were independently associated with behavioral intention, with self-efficacy as the strongest determinant of intention to increase physical activity (aBeta 0.40; 95% CI 0.12-0.71), adapt a healthy diet (aBeta 0.49; 95% CI 0.23-0.75), and quit smoking (aBeta 0.51; 95% CI 0.13-0.88). Intention to change tended to be associated with actual health-related behavior change. CONCLUSION: Self-efficacy, fear, and response-efficacy were determinants of intention to change health-related behavior after TIA or ischemic stroke. PRACTICE IMPLICATIONS: These determinants of intention to change health-related behavior after TIA or ischemic stroke should be taken into account in the development of future interventions promoting health-related behavior change in these group of patients. PMID- 26561312 TI - Dietary Isoflavones as Modulators of Drug Metabolizing Enzymes and Transporters: Effect on Prescription Medicines. AB - Isoflavones are the most widely consumed phytoestrogens. Besides being a dietary constituent, their consumption has been increasing in the form of herbal supplements and as promising alternatives to hormonal replacement therapy, in conjunction with prescription medicines. Isoflavones are extensively metabolized by phase I and II enzymes and are substrates of drug transporters. At high concentrations isoflavones may interact with drug metabolizing enzymes and drug transporters and modulate their activity, thus, altering the absorption, metabolism, distribution, excretion and toxicity profile of the co-administered drugs. This review summarizes the up-to-date literature of isoflavone-drug interactions giving insight into the possible mechanisms of interactions, in vitro-in vivo correlation and their implications on clinical outcomes. PMID- 26561313 TI - Neutrophil CD64 for the diagnosis of organizing pneumonia in patients with rheumatoid arthritis. PMID- 26561314 TI - Metabolomics-Based Analysis of Banana and Pear Ingestion on Exercise Performance and Recovery. AB - Bananas and pears vary in sugar and phenolic profiles, and metabolomics was utilized to measure their influence on exercise performance and recovery. Male athletes (N = 20) cycled for 75 km while consuming water (WATER), bananas (BAN), or pears (PEAR) (0.6 g carbohydrate/kg each hour) in randomized order. UPLC-MS/MS and the library of purified standards maintained by Metabolon (Durham, NC) were used to analyze metabolite shifts in pre- and postexercise (0-h, 1.5-h, 21-h) blood samples. Performance times were 5.0% and 3.3% faster during BAN and PEAR versus WATER (P = 0.018 and P = 0.091, respectively), with reductions in cortisol, IL-10, and total leukocytes, and increases in blood glucose, insulin, and FRAP. Partial Least Square Discriminant Analysis (PLS-DA) showed a distinct separation between trials immediately (R(2)Y = 0.877, Q(2)Y = 0.457) and 1.5-h postexercise (R(2)Y = 0.773, Q(2)Y = 0.441). A total of 107 metabolites (primarily lipid-related) increased more than 2-fold during WATER, with a 48% and 52% reduction in magnitude during BAN and PEAR recovery (P < 0.001). Increases in metabolites unique to BAN and PEAR included fructose and fruit constituents, and sulfated phenolics that were related to elevated FRAP. These data indicate that BAN and PEAR ingestion improves 75-km cycling performance, attenuates fatty acid utilization and oxidation, and contributes unique phenolics that augment antioxidant capacity. PMID- 26561315 TI - A cohesive analysis of DNA/RNA sequences via entropy, energetics and spectral domain methods to assess genomic features across single viral diversity. AB - In virology context, a particular virus may prevail in different forms of serotypes (as in the case of dengue 1-4 viral strains) with common and distinct genomic features. Finding such genomic details of a serogroup is useful in knowing related information for unique vaccine designs compatible for immunity across the viral diversity. For robust comparison of genomes of serovars of a virus in order to decide on their common and differential genomic details, proposed here is a set of sequence analyses exercised side-by-side via entropy, energetic and spectral-domain methods. Results obtained thereof with dengue viral serotypes, namely DEN1, DEN2, DEN3 and DEN4, are presented. Hence, inferences on distinct as well as common features extracted are annotated and indicated for possible vaccine design applications. PMID- 26561316 TI - Classification of PCR-SSCP bands in T2DM by probabilistic neural network: a reliable tool. AB - A Probabilistic Neural Network (PNN) is a statistical algorithm and consists of a grouping of multi-class data. The conventional method of detection of DNA mutations by the human eye may not detect the minute variations in PCR-SSCP bands, which may lead to false positive or false negative results. The detection by photographic images may contain a blare (noise) caused during the time of photography; therefore, image processing techniques were used to reduce image noise. PCR-SSCP gels of T2DM patients (n = 100) and controls (n = 100) were initially photographed with equal ratio of pixels and later subjected to a two stage analysis: feature extraction and PNN. The evaluation of the results was done by quality training and the accuracy was up to 95%, and the human eye analysis showed 80% mutation detection rate. This study proves to be very reliable and gives accurate and fast detection for mutation analysis in diabetes. This method could be extended for analysis in other human diseases. PMID- 26561317 TI - An interactomic approach for identification of putative drug targets in Listeria monocytogenes. AB - A wide variety of human population is infected with Listeria monocytogenes, which causes listeriosis, a deadly disease with mortality rate of about 30%. The major hindrance to cure listeriosis is the unavailability of specific or selectable drug targets. At present, antibiotics used to cure the disease are not specific and insufficient to manage the disease efficiently. Therefore, in order to search specific drugs, here, we used interactome analysis to search specific drug targets which may provide novel templates for drug designing having better efficacy without any potential adverse effects. The complete genome of L. monocytogenes having 2846 proteins has been analysed. We found 11 proteins as putative drug targets. The sequence and interactome analyses revealed that 11 proteins are non-homologous to human, but essential for pathogen and hence may be considered as potential therapeutic targets. PMID- 26561318 TI - Receptor-based 3D-QSAR approach to find selectivity features of flexible similar binding sites: case study on MMP-12/MMP-13. AB - Design of selective matrix metalloproteinases (MMPs) inhibitors is still a challenging task because of binding pocket similarities and flexibility among MMPs family. To overcome this issue we try to generate a (three-dimensional quantitative structure activity relationship) 3D-QSAR model that might reflect, at least in part, the differential properties of MMP-12 and MMP-13 active sites compared to each other. The different alignment rules were applied for CoMFA/CoMSIA model development. In an approach the best docked poses were followed by alignment based on their zinc binding group. As it was suggested by comparison of CoMSIA contour maps of MMP-12 with MMP-13, the ligand based approach can find more detailed features of specificity for MMPs that have similar highly flexible active sites, than solely analysis of available crystal structures. The residues Val(194), Leu(214) and Thr(220) of MMP-13 were suggested to be investigated for flexibility upon binding of different ligands. PMID- 26561320 TI - Is HNF4A a candidate to study zinc finger protein slug? AB - Protein-Protein Interactions (PPI) play a crucial role in deciphering function besides identifying candidates. While the experimental analysis is often time consuming involving number of experiments like pulldown assays, they are not necessarily limiting the ability to detect novel protein interactors. In this work, we discuss the role and putative interactors of SNAI2, a slug protein which is involved in the development of cancer progression. The protein interactions have been deciphered by domain pair exclusion method which gives confidence to already precluded interaction pairs. Additionally, conservation patterns of the slug protein have also been analysed by estimating site-specific evolutionary rates at structural level. Based upon the computational analysis, we consider HNF4A could be a putative candidate to study zinc finger protein slug. We believe, this candidate study augmented with structural conservation will definitely provide novel insights into the design and discovery of new interactions for zinc finger class of proteins besides providing possible clues for discovery of various cancer types associated with this class of proteins. PMID- 26561319 TI - Opposite nucleotide usage biases in different parts of the Corynebacterium diphtheriae spaC gene. AB - In this work we described a bacterial open reading frame with two different directions of nucleotide usage biases in its two parts. The level of GC-content in third codon positions (3GC) is equal to 40.17 +/- 0.22% during the most of the length of Corynebacterium diphtheriae spaC gene. However, in the 3'-end of the same gene (from codon #1600 to codon #1873) 3GC level is equal to 64.61 +/- 0.91%. Using original methodology ('VVTAK Sliding window' and 'VVTAK VarInvar') we approved that there is an ongoing mutational AT-pressure during the most of the length of spaC gene (up to codon #1599), and there is an ongoing mutational G pressure in the 3′-end of spaC. Intragenic promoters predicted by three different methods may be the cause of the differences in preferable types of nucleotide mutations in spaC parts because of their autonomous transcription. PMID- 26561321 TI - Influence of soil conditions on dissolved organic matter leached from forest and wetland soils: a controlled growth chamber study. AB - This study investigated the effects of various soil conditions, including drying rewetting, nitrogen deposition, and temperature rise, on the quantities and the composition of dissolved organic matter leached from forest and wetland soils. A set of forest and wetland soils with and without the nitrogen deposition were incubated in the growth chambers under three different temperatures. The moisture contents were kept constant, except for two-week drying intervals. Comparisons between the original and the treated samples revealed that drying-rewetting was a crucial environmental factor driving changes in the amount of dissolved organic carbon (DOC). The DOC was also notably increased by the nitrogen deposition to the dry forest soil and was affected by the temperature of the dry wetland soil. A parallel factor (PARAFAC) analysis identified three sub-fractions of the fluorescent dissolved organic matter (FDOM) from the fluorescence excitation emission matrices (EEMs), and their compositions depended on drying-rewetting. The data as a whole, including the DOC and PARAFAC components and other optical indices, were possibly explained by the two main variables, which were closely related with the PARAFAC components and DOC based on principal component analysis (PCA). Our results suggested that the DOC and PARAFAC component information could provide a comprehensive interpretation of the changes in the soil-leached DOM in response to the different environmental conditions. PMID- 26561323 TI - Alteration and element mobility at microbe-mineral interfaces. PMID- 26561322 TI - Does residual H2O2 result in inhibitory effect on enhanced anaerobic digestion of sludge pretreated by microwave-H2O2 pretreatment process? AB - This study investigated the effects of residual H2O2 on hydrolysis-acidification and methanogenesis stages of anaerobic digestion after microwave-H2O2 (MW-H2O2) pretreatment of waste activated sludge (WAS). Results showed that high sludge solubilization at 35-45 % was achieved after pretreatment, while large amounts of residual H2O2 remained and refractory compounds were thus generated with high dosage of H2O2 (0.6 g H2O2/g total solids (TS), 1.0 g H2O2/g TS) pretreatment. The residual H2O2 not only inhibited hydrolysis-acidification stage mildly, such as hydrolase activity, but also had acute toxic effect on methanogens, resulting in long lag phase, low methane yield rate, and no increase of cumulative methane production during the 30-day BMP tests. When the low dosage of H2O2 at 0.2 g H2O2/g TS was used in MW-H2O2 pretreatment, sludge anaerobic digestion was significantly enhanced. The cumulative methane production increased by 29.02 %, but still with a lag phase of 1.0 day. With removing the residual H2O2 by catalase, the initial lag phase of hydrolysis-acidification stage decreased from 1.0 to 0.5 day. PMID- 26561324 TI - Clarification of colloidal and suspended material in water using triethanolamine modified maize tassels. AB - Suspended particles in water are a major concern in global pollution management. They affect the appreciation of water due to clarity, photosynthesis, and poor oxygen environment rendering water unsuitable for aquatic animals. Some suspended materials contain functional groups capable of forming complex compounds with metals making them available for poisoning. Such material promotes the growth of bacteria and fouling that give rise to unpleasant taste and odor of the water and thus requires removal. Removal of suspended solids is normally achieved through sedimentation or filtration. However, some suspended colloidal particles are very stable in water and cannot settle while others are able to pass through the filter due to small size, hence difficult to remove. This study investigated the use of triethanolamine-modified maize tassels to form a flocculent for their removal. The modified maize tassels were characterized using Fourier transform infrared (FTIR), and it was found that the triethanolamine was anchored within the cellulose structure of the maize tassels. Clarification parameters such as settling time, reagent dosage, and pH were investigated. The best clarification was at a pH of 6.0 with clearance being less than in 30 min. The optimal flocculent dosage was found to be 3.5 ml of the material, showing that the material has a potential of enhancing clarity in polluted water. PMID- 26561325 TI - Impacts of urbanization on the distribution of heavy metals in soils along the Huangpu River, the drinking water source for Shanghai. AB - We investigated the horizontal and vertical distribution of heavy metals (Hg, Pb, Zn, Cu, Cd, As, Ni, and Cr) in soils in the water source protection zone for Shanghai to study the origins of these metals, their connections with urbanization, and their potential risk posed on the ecosystem. Determination of metal concentrations in 50 topsoil samples and nine soil profiles indicated that Hg, Pb, Zn, and Cu were present in significantly higher concentrations in topsoil than in deep soil layers. The spatial distributions of Hg, Pb, Zn, and Cu and contamination hotspots for these metals in the study area were similar to those near heavy industries and urban built-up areas. Emissions from automobiles resulted in increased soil concentrations of Cu, Pb, and Zn along roadsides, while high concentrations of Hg in the soil resulted from recent atmospheric deposition. Calculation of the potential ecological risk indicated that the integrative risk of these heavy metals in most areas was low, but a few sites surrounding high density of factories showed moderate risks. PMID- 26561327 TI - Characterization of biodegradable poly-3-hydroxybutyrate films and pellets loaded with the fungicide tebuconazole. AB - Biodegradable polymer poly(3-hydroxybutyrate) (P3HB) has been used as a matrix to construct slow-release formulations of the fungicide tebuconazole (TEB). P3HB/TEB systems constructed as films and pellets have been studied using differential scanning calorimetry, X-ray structure analysis, and Fourier transform infrared spectroscopy. TEB release from the experimental formulations has been studied in aqueous and soil laboratory systems. In the soil with known composition of microbial community, polymer was degraded, and TEB release after 35 days reached 60 and 36 % from films and pellets, respectively. That was 1.23 and 1.8 times more than the amount released to the water after 60 days in a sterile aqueous system. Incubation of P3HB/TEB films and pellets in the soil stimulated development of P3HB-degrading microorganisms of the genera Pseudomonas, Stenotrophomonas, Variovorax, and Streptomyces. Experiments with phytopathogenic fungi F. moniliforme and F. solani showed that the experimental P3HB/TEB formulations had antifungal activity comparable with that of free TEB. PMID- 26561326 TI - The toxic effect of cypermethrin, amitraz and combinations of cypermethrin amitraz in rats. AB - In this study, the effects of cypermethrin (CYP), amitraz (AMT) and combined cypermethrin-amitraz (CYP-AMT) on some serum biochemical, oxidative stress and drug-metabolising parameters were investigated in male Wistar albino rats. CYP, AMT and combined CYP-AMT were administered at doses of 80 mg kg(-1) bw(-1) of CYP and 170 mg kg(-1) bw(-1) of AMT for 1 day (single dose), and at doses of 12 mg kg(-1) bw(-1) of CYP and 25 mg kg(-1) bw(-1) of AMT for 40 days by oral gavage. Oxidative stress (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glucose-6-phosphate dehydrogenase (G6PD)), serum biochemical (glucose, triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), blood urea nitrogen (BUN), creatinine, asparatate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein, albumin) in blood/tissues (liver, kidney, brain, spleen and testis) and hepatic drug metabolising (cytochrome P450 2E1 (CYP2E1), NADH-cytochrome b5 reductase (CYPb5), NADPH-cytochrome c reductase/NADPH cytocrome P450 reductase (CYTC), glutathione S transferase (GST), glutathione (GSH)) parameters were measured in liver samples taken on days 1 and 40. In result, it was determined that CYP, AMT and their combinations led to significant changes in the parameters investigated, and it was ascertained that long-term exposure to insecticides and the administration of insecticide combinations produced greater toxic effects in comparison with the administration of insecticides alone. PMID- 26561328 TI - Microbial degradation of decabromodiphenyl ether (DBDE) in soil slurry microcosms. AB - Decabromodiphenyl ether (DBDE), which has been identified as an endocrine disrupting compound, is used as brominated flame retardant, and this can result in serious bioaccumulation within ecological systems. The objective of this study was to explore DBDE bioremediation (25 mg/kg) using laboratory scale soil slurry microcosms. It was found that effective biodegradation of DBDE occurred in all microcosms. Various biometabolites were identified, namely polybrominated diphenyl ethers congeners and hydroxylated brominated diphenyl ether. Reductive debrominated products such as tri-BDE to hepta-BDE congeners were also detected, and their total concentrations ranged from 77.83 to 91.07 ng/g. The mechanism of DBDE biodegradation in soil slurry microcosms is proposed to consist of a series of biological reactions involving hydroxylation and debromination. Catechol 2,3 oxygenase genes, which are able to bring about meta-cleavage at specific unbrominated locations in carbon backbones, were identified as present during the DBDE biodegradation. No obvious effect on the ecological functional potential based on community-level physiological profiling was observed during DBDE biodegradation, and one major facultative Pseudomonas sp. (99 % similarity) was identified in the various soil slurry microcosms. These findings provide an important basis that should help environmental engineers to design future DBDE bioremediation systems that use a practical microcosm system. A bacterial-mixed culture can be selected as part of the bioaugmentation process for in situ DBDE bioremediation. A soil/water microcosm system can be successfully applied to carry out ex situ DBDE bioremediation. PMID- 26561329 TI - Response of N2O emissions to elevated water depth regulation: comparison of rhizosphere versus non-rhizosphere of Phragmites australis in a field-scale study. AB - Emissions of nitrous oxide (N2O) from wetland ecosystems are globally significant and have recently received increased attention. However, relatively few direct studies of these emissions in response to water depth-related changes in sediment ecosystems have been conducted, despite the likely role they play as hotspots of N2O production. We investigated depth-related differential responses of the dissolved inorganic nitrogen distribution in Phragmites australis (Cav.) Trin. ex Steud. rhizosphere versus non-rhizosphere sediments to determine if they accelerated N2O emissions and the release of inorganic nitrogen. Changes in static water depth and P. australis growth both had the potential to disrupt the distribution of porewater dissolved NH4 (+), NO3 (-), and NO2 (-) in profiles, and NO3 (-) had strong surface aggregation tendency and decreased significantly with depth. Conversely, the highest NO2 (-) contents were observed in deep water and the lowest in shallow water in the P. australis rhizosphere. When compared with NO3 (-), NH4 (+), and NO2 (-), fluxes from the rhizosphere were more sensitive to the effects of water depth, and both fluxes increased significantly at a depth of more than 1 m. Similarly, N2O emissions were obviously accelerated with increasing depth, although those from the rhizosphere were more readily controlled by P. australis. Pearson's correlation analysis showed that water depth was significantly related to N2O emission and NO2 (-) fluxes, and N2O emissions were also strongly dependent on NO2 (-) fluxes (r = 0.491, p < 0.05). The results presented herein provide new insights into inorganic nitrogen biogeochemical cycles in freshwater sediment ecosystems. PMID- 26561330 TI - Composite sequential Monte Carlo test for post-market vaccine safety surveillance. AB - Group sequential hypothesis testing is now widely used to analyze prospective data. If Monte Carlo simulation is used to construct the signaling threshold, the challenge is how to manage the type I error probability for each one of the multiple tests without losing control on the overall significance level. This paper introduces a valid method for a true management of the alpha spending at each one of a sequence of Monte Carlo tests. The method also enables the use of a sequential simulation strategy for each Monte Carlo test, which is useful for saving computational execution time. Thus, the proposed procedure allows for sequential Monte Carlo test in sequential analysis, and this is the reason that it is called 'composite sequential' test. An upper bound for the potential power losses from the proposed method is deduced. The composite sequential design is illustrated through an application for post-market vaccine safety surveillance data. PMID- 26561331 TI - Depression and Mood Disorder Among African American and White Women--Reply. PMID- 26561333 TI - The contractile lability of smooth muscle in asthmatic airway hyperresponsiveness. AB - The contractile capacity of airway smooth muscle is not fixed but modulated by an impressive number of extracellular inflammatory mediators. Targeting the transient component of airway hyperresponsiveness ascribed to this contractile lability of ASM is a quest of great promises in order to alleviate asthma symptoms during inflammatory flares. However, owing to the plethora of mediators putatively involved and the molecular heterogeneity of asthma, it is more likely that many mediators conspire to increase the contractile capacity of ASM, each of which contributing to a various extent and in a time-varying fashion in individuals suffering from asthma. The task of identifying a common mend for a tissue rendered hypercontractile by imponderable assortments of inflammatory mediators is puzzling. PMID- 26561332 TI - Yersinia pseudotuberculosis infection in Kawasaki disease and its clinical characteristics. AB - BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. Reportedly, there is an association between KD and Yersinia pseudotuberculosis (YPT). Steroid therapy for KD patients with high risk of cardiac sequelae (CS) has been reported; however, the number of reports is limited. METHODS: We conducted a prospective study of 108 patients with newly diagnosed KD in one year to determine how many KD patients have positive anti-YPT antibody titers and/or positive anti-YPT-derived mitogen (YPM) antibody titers. In addition, we tried to identify clinical differences between KD patients in whom YPT infection was or not a contributing factor. We also compared clinical characteristics of patients treated with the protocol of the Randomized controlled trial to Assess Immunoglobulin plus Steroid Efficacy for Kawasaki disease (RAISE) study (RAISE group) and with the conventional Intravenous immunoglobulin (IVIG) protocol (conventional group). RESULTS: Eleven patients (10%) were positive for anti-YPT and/or anti-YPM antibodies (positive group) and 97 (90%) were negative (negative group). Cardiac sequelae (CS) occurred significantly more frequently in the positive than the negative group (two patients, 18% vs one patient, 1%, p = 0.027). Forty patients were in the RAISE group. Two of 40 (5%) in the RAISE group and one of 68 (1.47%) in the conventional group had CS (p = 0.55). CONCLUSIONS: KD patients with YPT infection had CS significantly more frequently and treatment with RAISE protocol did not decrease the frequency of CS in our cohort, nor did YPT infection affect risk scores of no response to IVIG. However, our sample size was overly small to draw such conclusions. Further investigation in a larger cohort is necessary to confirm our findings. Additionally, further research is needed to determine whether early diagnosis of YPT can prevent KD from developing and reduce the incidence of CS. PMID- 26561334 TI - Detection of urinary estrogen conjugates and creatinine using near infrared spectroscopy in Bornean orangutans (Pongo Pygmaeus). AB - For promoting in situ conservation, it is important to estimate the density distribution of fertile individuals, and there is a need for developing an easy monitoring method to discriminate between physiological states. To date, physiological state has generally been determined by measuring hormone concentration using radioimmunoassay or enzyme immunoassay (EIA) methods. However, these methods have rarely been applied in situ because of the requirements for a large amount of reagent, instruments, and a radioactive isotope. In addition, the proper storage of the sample (including urine and feces) on site until analysis is difficult. On the other hand, near infrared (NIR) spectroscopy requires no reagent and enables rapid measurement. In the present study, we attempted urinary NIR spectroscopy to determine the estrogen levels of orangutans in Japanese zoos and in the Danum Valley Conservation Area, Sabah, Malaysia. Reflectance NIR spectra were obtained from urine stored using a filter paper. Filter paper is easy to use to store dried urine, even in the wild. Urinary estrogen and creatinine concentrations measured by EIA were used as the reference data of partial least square (PLS) regression of urinary NIR spectra. High accuracies (R(2) > 0.68) were obtained in both estrogen and creatinine regression models. In addition, the PLS regressions in both standards showed higher accuracies (R(2) > 0.70). Therefore, the present study demonstrates that urinary NIR spectra have the potential to estimate the estrogen and creatinine concentrations. PMID- 26561335 TI - DNA Triplexes That Bind Several Cofactor Molecules. AB - Cofactors are critical for energy-consuming processes in the cell. Harnessing such processes for practical applications requires control over the concentration of cofactors. We have recently shown that DNA triplex motifs with a designed binding site can be used to capture and release nucleotides with low micromolar dissociation constants. In order to increase the storage capacity of such triplex motifs, we have explored the limits of ligand binding through designed cavities in the oligopurine tract. Oligonucleotides with up to six non-nucleotide bridges between purines were synthesized and their ability to bind ATP, cAMP or FAD was measured. Triplex motifs with several single-nucleotide binding sites were found to bind purines more tightly than triplexes with one large binding site. The optimized triplex consists of 59 residues and four C3-bridges. It can bind up to four equivalents of ligand with apparent Kd values of 52 uM for ATP, 9 uM for FAD, and 2 uM for cAMP. An immobilized version fuels bioluminescence via release of ATP at body temperature. These results show that motifs for high-density capture, storage and release of energy-rich biomolecules can be constructed from synthetic DNA. PMID- 26561336 TI - Inhibition of A20 expression in tumor microenvironment exerts anti-tumor effect through inducing myeloid-derived suppressor cells apoptosis. AB - Myeloid-derived suppressor cells (MDSCs) are known to play important roles in the development of immunosuppressive tumor microenvironment. A20 is a zinc-finger protein which could negatively regulate apoptosis in several cell types. However, the role of A20 in tumor microenvironment remains largely unknown. In this study, we found that A20 was over-expressed in MDSCs. The treatment of tumor-bearing mice with small interfering RNA targeting A20 (si-A20) inhibited the growth of tumors. The infiltration of MDSCs was dramatically reduced after si-A20 treatment, as compared to control groups, whereas the numbers of dendritic cells and macrophages were not affected. Also, injection of si-A20 improved T cell mediated tumor-specific immune response. Depletion of MDSCs with anti-Gr1 antibody showed similar antitumor effect and improved T cell response. TNF-alpha was highly expressed after si-A20 injection. Furthermore, si-A20 induced apoptosis of MDSCs in the presence of TNF-alpha both in vivo and in vitro. Cleaved Caspase-3 and Caspase-8 were elevated with the activation of JNK pathway after the induction of MDSC apoptosis by si-A20. Thus, our findings suggested that knockdown of A20 in tumor site inhibited tumor growth at least through inducing the apoptosis of MDSCs. A20 might be a potential target in anticancer therapy. PMID- 26561338 TI - Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. AB - BACKGROUND: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9 tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. OBJECTIVES: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. SEARCH METHODS: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included 23 RCTs. Most were of cross over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. AUTHORS' CONCLUSIONS: Cannabis-based medications may be useful for treating refractory chemotherapy induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions. PMID- 26561339 TI - Identifying people with diabetes at high risk of blindness and amputation. PMID- 26561337 TI - Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. AB - INTRODUCTION: The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART), would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. DISCUSSION: This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI) as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. CONCLUSIONS: Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of an ATI is not ideal. PMID- 26561340 TI - Parasitization by Sauroplasma sp. (Apicomplexa: Haemohormidiidae) in Chelonian Podocnemis expansa (Testudines: Podocnemididae) in the Brazilian Amazon. AB - The prevalence and parasitemia of the piroplasm Sauroplasma sp. were evaluated in the Amazon chelonian Podocnemis expansa in Brazil. Samples were collected from 75 chelonians from 3 locations, including a commercial breeding facility, an indigenous subsistence breeding facility, and a wild population. Sauroplasma were found in 72% (54/75) of the chelonians, and the prevalence varied among the sampling sites. No significant correlations were found between the prevalence and the sex and body condition index of the chelonians. The mean parasitemia rate was 44.14/2,000 erythrocytes (2.2%), and no significant correlation was found between the parasitemia and sex and body condition index of the chelonians. These results suggest that the parasite is not pathogenic to P. expansa. No ectoparasites were found in the animals evaluated in the present study; however, due to the aquatic habit of the chelonian, it is likely that the piroplasm is transmitted by leeches and not by ticks, as would be expected for piroplasms. PMID- 26561341 TI - CD40 ligand-expressing recombinant vaccinia virus promotes the generation of CD8(+) central memory T cells. AB - Central memory CD8(+) T cells (TCM ) play key roles in the protective immunity against infectious agents, cancer immunotherapy, and adoptive treatments of malignant and viral diseases. CD8(+) TCM cells are characterized by specific phenotypes, homing, and proliferative capacities. However, CD8(+) TCM -cell generation is challenging, and usually requires CD4(+) CD40L(+) T-cell "help" during the priming of naive CD8(+) T cells. We have generated a replication incompetent CD40 ligand-expressing recombinant vaccinia virus (rVV40L) to promote the differentiation of human naive CD8(+) T cells into TCM specific for viral and tumor-associated antigens. Soluble CD40 ligand recombinant protein (sCD40L), and vaccinia virus wild-type (VV WT), alone or in combination, were used as controls. Here, we show that, in the absence of CD4(+) T cells, a single "in vitro" stimulation of naive CD8(+) T cells by rVV40L-infected nonprofessional CD14(+) antigen presenting cells promotes the rapid generation of viral or tumor associated antigen-specific CD8(+) T cells displaying TCM phenotypic and functional properties. These observations demonstrate the high ability of rVV40L to fine tune CD8(+) mediated immune responses, and strongly support the use of similar reagents for clinical immunization and adoptive immunotherapy purposes. PMID- 26561342 TI - Prospective randomized controlled trial to compare 3-dimensional conformal radiotherapy to intensity-modulated radiotherapy in head and neck squamous cell carcinoma: Long-term results. AB - BACKGROUND: Grade >=2 acute xerostomia between 3D conformal radiotherapy (RT) and intensity-modulated radiotherapy (IMRT) was evaluated in patients with head and neck squamous cell carcinomas (HNSCCs) treated radically. METHODS: Between 2005 and 2007, 59 patients with HNSCC (T1-3, N0-2b) were randomized to IMRT or 3D-RT. On RT, weekly xerostomia, dysphagia, dermatitis, and mucositis were graded by Radiation Therapy Oncology Group (RTOG) acute toxicity criteria. Patients underwent examination under anesthesia, positron emission tomography (PET)-CT, and toxicity assessments per protocol (NCT00652613) thereafter. RESULTS: Incidence of grade >=2 xerostomia at 8 weeks posttreatment was significantly lower with IMRT compared with 3D conformal RT (24% vs 53%; p = .024). At subsequent follow-up, significantly fewer patients receiving IMRT had grade >=2 xerostomia. Long-term weight loss was higher in patients in the 3D conformal RT arm compared to IMRT (50% vs 21%; p = .038). Disease-related outcomes between arms (median follow-up, 70 months) were similar. CONCLUSION: IMRT significantly reduces incidence of acute and late grade >=2 xerostomia in patients with HNSCC. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1481-E1487, 2016. PMID- 26561343 TI - Coated platelets and severe haemophilia A bleeding phenotype: Is there a connection? AB - INTRODUCTION: Coated platelets are a subpopulation of platelets that possess highly prothrombotic properties. Previous observational data suggest that bleeding phenotype in severe haemophilia A is associated with coated platelet levels. Haemophilia A patients with higher coated platelet levels may have a mild bleeding phenotype; those with lower levels may have a more severe bleeding phenotype. AIM: The aim of the study was to test the hypothesis that coated platelet levels are correlated with clinical bleeding phenotype. METHODS: This cross-sectional, observational study enrolled 20 severe haemophilia A patients, including 15 with severe and five with a mild bleeding phenotype, and a control group of 12 healthy volunteers. The haemophilia bleeding phenotype was determined by the patient's medical history and haemophilia treatment centre records. Blood was obtained from each patient by venipuncture and platelets were analysed by flow cytometry. RESULTS: Patients categorized as having a severe bleeding phenotype experienced a median eight bleeds per year compared to one bleed annually in the mild bleeding phenotype group. Both groups had similar total platelet counts and fibrinogen levels. There was no difference in coated platelet percentage between severe and mild bleeding phenotype (17 and 16% respectively), however, both groups had significantly lower % coated platelets compared to controls (44%, P < 0.0001). CONCLUSION: Coated platelet levels were not associated with bleeding phenotype in this study; however, these data may suggest coated platelet levels are lower in haemophilia patients relative to healthy volunteers. PMID- 26561344 TI - COGNIZER: A Framework for Functional Annotation of Metagenomic Datasets. AB - BACKGROUND: Recent advances in sequencing technologies have resulted in an unprecedented increase in the number of metagenomes that are being sequenced world-wide. Given their volume, functional annotation of metagenomic sequence datasets requires specialized computational tools/techniques. In spite of having high accuracy, existing stand-alone functional annotation tools necessitate end users to perform compute-intensive homology searches of metagenomic datasets against "multiple" databases prior to functional analysis. Although, web-based functional annotation servers address to some extent the problem of availability of compute resources, uploading and analyzing huge volumes of sequence data on a shared public web-service has its own set of limitations. In this study, we present COGNIZER, a comprehensive stand-alone annotation framework which enables end-users to functionally annotate sequences constituting metagenomic datasets. The COGNIZER framework provides multiple workflow options. A subset of these options employs a novel directed-search strategy which helps in reducing the overall compute requirements for end-users. The COGNIZER framework includes a cross-mapping database that enables end-users to simultaneously derive/infer KEGG, Pfam, GO, and SEED subsystem information from the COG annotations. RESULTS: Validation experiments performed with real-world metagenomes and metatranscriptomes, generated using diverse sequencing technologies, indicate that the novel directed-search strategy employed in COGNIZER helps in reducing the compute requirements without significant loss in annotation accuracy. A comparison of COGNIZER's results with pre-computed benchmark values indicate the reliability of the cross-mapping database employed in COGNIZER. CONCLUSION: The COGNIZER framework is capable of comprehensively annotating any metagenomic or metatranscriptomic dataset from varied sequencing platforms in functional terms. Multiple search options in COGNIZER provide end-users the flexibility of choosing a homology search protocol based on available compute resources. The cross mapping database in COGNIZER is of high utility since it enables end-users to directly infer/derive KEGG, Pfam, GO, and SEED subsystem annotations from COG categorizations. Furthermore, availability of COGNIZER as a stand-alone scalable implementation is expected to make it a valuable annotation tool in the field of metagenomic research. AVAILABILITY AND IMPLEMENTATION: A Linux implementation of COGNIZER is freely available for download from the following links: http://metagenomics.atc.tcs.com/cognizer, https://metagenomics.atc.tcs.com/function/cognizer. PMID- 26561345 TI - Minocycline inhibits peritoneal macrophages but activates alveolar macrophages in acute pancreatitis. AB - Minocycline is a tetracycline antibiotic that, in addition to its antimicrobial function, has been reported to possess a relevant anti-inflammatory activity. Its effects have been extensively evaluated in inflammatory-related neurological diseases. Here, we evaluate its effect on the systemic inflammatory response in a model of experimental acute pancreatitis. Minocycline treatment significantly reduced the inflammation in pancreas and mesenterium, had no effect on the adipose tissue inflammation, and increased the inflammatory response in the lung. These differences seem to be related with different effects exerted on peritoneal and alveolar macrophages. In vitro, minocycline reduced the expression of IL 1beta and inhibit the activation of nuclear factor kappa B (NF-kappaB) on peritoneal macrophages, while it had no effect on alveolar macrophages. Our data indicates that although minocycline may be useful as a tool to control some inflammatory processes, differences on its effects depending on the population of macrophages involved in the process can be expected. In the particular case of acute pancreatitis, it could promote or potentiate inflammation in the lung so that its use does not appear to be recommended. PMID- 26561347 TI - Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma. AB - The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (>=10 IU/L) in 42.1% and LH levels >=8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P < .0001, .04), lomustine (CCNU; P = .002, 0.04), and procarbazine (P < .0001, .07). No significant correlation was found between FSH or LH levels and age or pubertal status at diagnosis. Mean FSH level was significantly lower in NHL survivors treated more recently: 6 +/- 5.1 IU/L in B NHL survivors treated since 1986 versus 12.3 +/- 5.4 IU/L for those treated before 1981 (P = .0001), and 6.8 +/- 9.6 IU/L in T-NHL survivors treated since 1989 versus 9.4 +/- 5.7 IU/L for those treated before 1989 (P = .035). In HL, mean FSH level was 12.4 +/- 9.9 IU/L following procarbazine containing chemotherapy versus 3.4 +/- 1.9 IU/L in the absence of procarbazine and increased significantly with the number of MOPP/OPPA (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone/Oncovin, procarbazine, and prednisone, and Adriamycin [doxorubicin]) courses received, from 6.8 +/- 5.7 IU/L for 1-2 MOPP/OPPA to 12.6 +/- 7.5 for 3-4 MOPP/OPPA and 19.6 +/- 13.3 for more than 4 MOPP/OPPA (P for trend = .006). Testicular toxicity of alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis. PMID- 26561346 TI - Simvastatin Impairs Insulin Secretion by Multiple Mechanisms in MIN6 Cells. AB - Statins are widely used in the treatment of hypercholesterolemia and are efficient in the prevention of cardiovascular disease. Molecular mechanisms explaining statin-induced impairment in insulin secretion remain largely unknown. In the current study, we show that simvastatin decreased glucose-stimulated insulin secretion in mouse pancreatic MIN6 beta-cells by 59% and 79% (p<0.01) at glucose concentration of 5.5 mmol/l and 16.7 mmol/l, respectively, compared to control, whereas pravastatin did not impair insulin secretion. Simvastatin induced decrease in insulin secretion occurred through multiple targets. In addition to its established effects on ATP-sensitive potassium channels (p = 0.004) and voltage-gated calcium channels (p = 0.004), simvastatin suppressed insulin secretion stimulated by muscarinic M3 or GPR40 receptor agonists (Tak875 by 33%, p = 0.002; GW9508 by 77%, p = 0.01) at glucose level of 5.5 mmol/l, and inhibited calcium release from the endoplasmic reticulum. Impaired insulin secretion caused by simvastatin treatment were efficiently restored by GPR119 or GLP-1 receptor stimulation and by direct activation of cAMP-dependent signaling pathways with forskolin. The effects of simvastatin treatment on insulin secretion were not affected by the presence of hyperglycemia. Our observation of the opposite effects of simvastatin and pravastatin on glucose-stimulated insulin secretion is in agreement with previous reports showing that simvastatin, but not pravastatin, was associated with increased risk of incident diabetes. PMID- 26561348 TI - Adaptive Evolution of Eel Fluorescent Proteins from Fatty Acid Binding Proteins Produces Bright Fluorescence in the Marine Environment. AB - We report the identification and characterization of two new members of a family of bilirubin-inducible fluorescent proteins (FPs) from marine chlopsid eels and demonstrate a key region of the sequence that serves as an evolutionary switch from non-fluorescent to fluorescent fatty acid-binding proteins (FABPs). Using transcriptomic analysis of two species of brightly fluorescent Kaupichthys eels (Kaupichthys hyoproroides and Kaupichthys n. sp.), two new FPs were identified, cloned and characterized (Chlopsid FP I and Chlopsid FP II). We then performed phylogenetic analysis on 210 FABPs, spanning 16 vertebrate orders, and including 163 vertebrate taxa. We show that the fluorescent FPs diverged as a protein family and are the sister group to brain FABPs. Our results indicate that the evolution of this family involved at least three gene duplication events. We show that fluorescent FABPs possess a unique, conserved tripeptide Gly-Pro-Pro sequence motif, which is not found in non-fluorescent fatty acid binding proteins. This motif arose from a duplication event of the FABP brain isoforms and was under strong purifying selection, leading to the classification of this new FP family. Residues adjacent to the motif are under strong positive selection, suggesting a further refinement of the eel protein's fluorescent properties. We present a phylogenetic reconstruction of this emerging FP family and describe additional fluorescent FABP members from groups of distantly related eels. The elucidation of this class of fish FPs with diverse properties provides new templates for the development of protein-based fluorescent tools. The evolutionary adaptation from fatty acid-binding proteins to fluorescent fatty acid-binding proteins raises intrigue as to the functional role of bright green fluorescence in this cryptic genus of reclusive eels that inhabit a blue, nearly monochromatic, marine environment. PMID- 26561349 TI - Innovation Through Tradition: Rediscovering the "Humanist" in the Medical Humanities. AB - Throughout its fifty-year history, the role of the medical humanist and even the name "medical humanities" has remained raw, dynamic and contested. What do we mean when we call ourselves "humanists" and our practice "medical humanities?" To address these questions, we turn to the concept of origin narratives. After explaining the value of these stories, we focus on one particularly rich origin narrative of the medical humanities by telling the story of how a group of educators, ethicists, and scholars struggling to define their relatively new field rediscovered the studia humanitatis, a Renaissance curriculum for learning and teaching. Our origin narrative is composed of two intertwined stories-the history of the studia humanitatis itself and the story of the scholars who rediscovered it. We argue that as an origin narrative the studia humanitatis grounds the medical humanities as both an engaged moral practice and pedagogical project. In the latter part of the paper, we use this origin narrative to show how medical humanists working in translational science can use their understanding of their historical roots to do meaningful work in the world. PMID- 26561350 TI - Emergency management of high-energy pelvic trauma. AB - A fractured pelvis can be a significant cause of patient morbidity and mortality. Injuries to the pelvis that result from high-energy trauma can be devastating, and patients often have other associated injuries. This article reviews the pathophysiology of pelvic fractures and how to classify and manage them in the emergency setting in order to improve patient outcomes. PMID- 26561351 TI - Intermittent steroid inhalation for the treatment of childhood asthma. AB - Inhaled corticosteroids have long been considered a mainstay of therapy for asthma in children. However, concerns over long-term side effects of chronic steroid administration have led providers to turn to intermittent dosing of these medications in an attempt to treat exacerbations while limiting total corticosteroid received. The data have been somewhat mixed in this area, likely at least partially due to the difficulty providers have in classifying asthma phenotypes in young children. This review will analyze the evidence for chronic daily inhaled corticosteroid use, intermittent inhaled corticosteroid use, and dynamic dosing approaches utilizing inhaled corticosteroid/long-acting beta agonist combination therapy. PMID- 26561352 TI - Evaluation of WO2015042088 A1 - a novel urea-based scaffold for TrkA inhibition. AB - Tropomyosin receptor kinases (TrkA/B/C) are involved in the development and maintenance of the nervous system. TrkA is a target for chronic pain treatment due to the central position of the nerve growth factor (NGF)/TrkA pathway in nociception. Clinical evidence points toward mutated oncogenic Trk fusion proteins retaining intact kinase domains as relevant targets for cancer treatment. Merck pursues Trk inhibitors for inflammatory and neuropathic pain treatment and has previously reported type I and II selective pan-Trk inhibitors. This is the fifth filing by Merck disclosing urea-based Trk inhibitor series. This application claims nonsymmetric 1-(9H-fluoren-9-yl)urea and 1-(9H-xanthen-9 yl)urea derivatives containing a wide range of 5- and 6-membered bi- or tri heterocyclic fragments as TrkA inhibitors for the treatment of Trk-related conditions. The exemplified compounds display IC50 values ranging from 27 to 4800 nM against TrkA. The TrkA inhibitors claimed confirm the emergence of nonsymmetric ureas lacking the hinge-binding motif as a favored Trk inhibitor structure. The compounds exemplified will likely be structurally optimized in the future. Despite the lack of selectivity profiling, the progression of the Trk inhibitor scaffold exploration by Merck also suggests that the compounds disclosed in this patent likely constitute non-adenosine triphosphate (ATP) competitive type III pan-Trk inhibitors. PMID- 26561353 TI - The role of common genetic variation in educational attainment and income: evidence from the National Child Development Study. AB - We investigated the role of common genetic variation in educational attainment and household income. We used data from 5,458 participants of the National Child Development Study to estimate: 1) the associations of rs9320913, rs11584700 and rs4851266 and socioeconomic position and educational phenotypes; and 2) the univariate chip-heritability of each phenotype, and the genetic correlation between each phenotype and educational attainment at age 16. The three SNPs were associated with most measures of educational attainment. Common genetic variation contributed to 6 of 14 socioeconomic background phenotypes, and 17 of 29 educational phenotypes. We found evidence of genetic correlations between educational attainment at age 16 and 4 of 14 social background and 8 of 28 educational phenotypes. This suggests common genetic variation contributes both to differences in educational attainment and its relationship with other phenotypes. However, we remain cautious that cryptic population structure, assortative mating, and dynastic effects may influence these associations. PMID- 26561354 TI - Evaluation of the impact of RNA preservation methods of spiders for de novo transcriptome assembly. AB - With advances in high-throughput sequencing technologies, de novo transcriptome sequencing and assembly has become a cost-effective method to obtain comprehensive genetic information of a species of interest, especially in nonmodel species with large genomes such as spiders. However, high-quality RNA is essential for successful sequencing, and sample preservation conditions require careful consideration for the effective storage of field-collected samples. To this end, we report a streamlined feasibility study of various storage conditions and their effects on de novo transcriptome assembly results. The storage parameters considered include temperatures ranging from room temperature to -80 degrees C; preservatives, including ethanol, RNAlater, TRIzol and RNAlater-ICE; and sample submersion states. As a result, intact RNA was extracted and assembly was successful when samples were preserved at low temperatures regardless of the type of preservative used. The assemblies as well as the gene expression profiles were shown to be robust to RNA degradation, when 30 million 150-bp paired-end reads are obtained. The parameters for sample storage, RNA extraction, library preparation, sequencing and in silico assembly considered in this work provide a guideline for the study of field-collected samples of spiders. PMID- 26561355 TI - Intensive Hemodialysis and Mortality Risk in Australian and New Zealand Populations. AB - BACKGROUND: Intensive hemodialysis (HD) is characterized by increased frequency and/or session length compared to conventional HD. Previous analyses from Australia and New Zealand did not suggest benefit with intensive HD, although recent research suggests that relationships have changed. We present updated analyses. STUDY DESIGN: Observational cohort study using marginal structural modeling to adjust for changes in renal replacement modality and time-varying medical comorbid conditions. SETTING & PARTICIPANTS: Adults initiating renal replacement therapy since March 31, 1996, followed up through December 31, 2012; this analysis included 40,842 patients over 2,187,689 patient-months. PREDICTOR: Time-varying renal replacement modality: conventional facility HD (<=3 times per week, <=6 hours per session), quasi-intensive facility HD (between conventional and intensive), intensive facility HD (>=5 times per week, any hours per session), conventional home HD, quasi-intensive home HD, intensive home HD, peritoneal dialysis, deceased donor kidney transplantation, and living donor kidney transplantation. OUTCOMES: Patient mortality, with a 3-month lag in primary analyses and 6- and 12-month lags in sensitivity analyses. RESULTS: Conventional facility HD was the reference group. Conventional home HD had a similar mortality risk. For quasi-intensive home HD, mortality risk was lower (HR, 0.56; 95% CI, 0.44-0.73). For intensive home HD, mortality risk was nonsignificantly lower in primary analyses and significantly lower using a 6 month lag (HR, 0.41; 95% CI, 0.20-0.85), but not using a 12-month lag. For quasi intensive facility HD, mortality risk was nonsignificantly lower in primary analyses, although significantly lower using 6- (HR, 0.41; 95% CI, 0.20-0.85) and 12-month lags (HR, 0.59; 95% CI, 0.44-0.80). Mortality risk was similar between intensive and conventional facility HD. For peritoneal dialysis, mortality risk was greater than for conventional facility HD (HR, 1.07; 95% CI, 1.03-1.12). Kidney transplantation had the lowest mortality risk. LIMITATIONS: Potential residual confounding from limited collection of comorbid condition, socioeconomic, and medication data. CONCLUSIONS: There is an emerging HD dose effect in Australia and New Zealand, with lower mortality risks associated with some of the more intensive HD regimens in these countries. PMID- 26561357 TI - Cell aging and kidney repair. PMID- 26561358 TI - Activity of the enantiomers of erythro-3-hydroxyaspartate at glutamate transporters and NMDA receptors. AB - The enantiomers of erythro-3-hydroxyaspartate were tested for activity at glutamate transporters and NMDA receptors. Both enantiomers inhibited glutamate transporters in rat hippocampal crude synaptosomes and elicited substrate-like activity at excitatory amino acid transporter 1, 2, and 3 as measured by voltage clamp in the Xenopus oocyte expression system. The enantiomers had similar affinities, but the D-enantiomer showed a lower maximal effect at excitatory amino acid transporter 1, 2, and 3 than the L-enantiomer. Surprisingly, D-erythro 3-hydroxyaspartate was a potent NMDA receptor agonist with an EC50 value in rat hippocampal neurons of 320 nM, whereas the L-enantiomer was 100-fold less potent. L-erythro-3-hydroxyaspartate showed activity at both glutamate transporters and NMDA receptors at concentrations that are reported to inhibit serine racemase, indicating a lack of selectivity. This enantiomeric pair may assist in shedding further light on the structural requirements for substrate activity at glutamate transporters and for agonist activity at NMDA receptors. The erythro enantiomers of 3-hydroxyaspartate had interesting and surprising effects on glutamate neurotransmitter systems. L-erythro-3-hydroxyaspartate had activity at both glutamate transporters (EAAT1/2/3) and NMDA receptors. D-erythro-3 hydroxyaspartate acted on EAATs, but was also identified as a highly potent NMDA receptor agonist. These enantiomers shed further light on the structural requirements for activity at EAATs and NMDA receptors. PMID- 26561356 TI - Racial Disparities in Access to and Outcomes of Kidney Transplantation in Children, Adolescents, and Young Adults: Results From the ESPN/ERA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) Registry. AB - BACKGROUND: Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: Data were derived from the ESPN/ERA EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged <=19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR: Racial background. OUTCOMES & MEASUREMENTS: Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS: 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS: No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS: We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups. PMID- 26561359 TI - Parental perceptions of congenital cardiovascular malformations in their children. AB - We assessed parental attitudes towards congenital cardiovascular malformations in their children in a cross-sectional study in Egypt. Parents face many problems related to concerns about their child's prognosis, but these associations with parental stress have never been evaluated in Egypt or examined in relation to religiosity in a predominantly Muslim society. Accordingly, we conducted interviews in Cairo with mothers of 99 sequential infants born with conotruncal heart malformations (cases) and 65 mothers of age-matched controls. The survey assessed healthcare access and usage, knowledge of congenital cardiovascular malformations, religiosity, the Locus of Control Scale, and the Parenting Stress Index. Results showed that 45% of the mothers of cases had correct knowledge about their child's diagnosis; 85% were satisfied with the clinical care; and 79% reported that the cost of care was burdensome. Compared with parents of cases, parents of controls were more likely to report stress overall and all its subscales. Regarding belief about locus of control over health, God as a determining factor was given the highest endorsement. Mothers in the congenital cardiovascular malformations group reported a higher level of parental locus of control than did those in the control group. The correlations between stress and locus of control were stronger in the control than in the case group. Religiosity was related neither to stress nor to locus of control. Future studies can explore the roles that personal, familial, and societal factors play in exacerbating or reducing stress levels among parents of sick children, particularly in developing countries where economic pressures are acute. PMID- 26561360 TI - A new approach for designing disease intervention strategies in metapopulation models. AB - We describe a new approach for investigating the control strategies of compartmental disease transmission models. The method rests on the construction of various alternative next-generation matrices, and makes use of the type reproduction number and the target reproduction number. A general metapopulation SIRS (susceptible-infected-recovered-susceptible) model is given to illustrate the application of the method. Such model is useful to study a wide variety of diseases where the population is distributed over geographically separated regions. Considering various control measures such as vaccination, social distancing, and travel restrictions, the procedure allows us to precisely describe in terms of the model parameters, how control methods should be implemented in the SIRS model to ensure disease elimination. In particular, we characterize cases where changing only the travel rates between the regions is sufficient to prevent an outbreak. PMID- 26561361 TI - Does the Heat Generation by the Thulium:Yttrium Aluminum Garnet Laser in the Irrigation Fluid Allow Its Use on the Upper Urinary Tract? An Experimental Study. AB - INTRODUCTION: The current experimental study aimed into evaluating the temperature raise of the irrigation fluid caused by the use of the Thulium:Yttrium aluminum garnet (Tm:YAG) laser. The study setting was designed to replicate conditions of upper urinary tract (UT) surgery. MATERIALS AND METHODS: An experimental setting was designed for the investigation of differences in the temperature of the irrigation fluid in different flow rates, laser power settings, and laser activation times and modes. The experimental configuration included a burette equipped with a micrometric stopcock, a thermocouple, and a modified 40-mL vessel. A Tm:YAG and Holmium:Yttrium aluminum garnet (Ho:YAG) laser devices were used. RESULTS: The Tm:YAG in the continuous mode and in power settings of 5, 10, and 20 W showed similar temperature changes during the 10 minute observation period. The temperatures of the Tm:YAG in the pulsed mode tended to range within similar levels (46.8 degrees C-61 degrees C) with the continuous mode (47.8 degrees C-68 degrees C) when power settings up to 20 W were considered. When the higher power settings (50 and 100 W) were investigated, the temperatures reached were significantly higher in both pulsed and continuous modes. The Ho:YAG showed similar temperatures in comparison to the Tm:YAG in all the flow rates and power settings. The temperatures ranged between 45.6 degrees C and 68.7 degrees C. CONCLUSION: The Tm:YAG in the pulsed and continuous mode with power settings up to 20 W seemed to have potential for UT use. By combining a power setting at the above limit and a low flow rate (as low as 2 mL/minute), it is possible to use the Tm:YAG with safety in terms of temperature. PMID- 26561363 TI - Low-wind and other microclimatic factors in near-road black carbon variability: A case study and assessment implications. AB - Airborne black carbon from urban traffic is a climate forcing agent and has been associated with health risks to near-road populations. In this paper, we describe a case study of black carbon concentration and compositional variability at and near a traffic-laden multi-lane highway in Cincinnati, Ohio, using an onsite aethalometer and filter-based NIOSH Method 5040 measurements; the former measured 1-min average black carbon concentrations and the latter determined the levels of organic and elemental carbon (OC and EC) averaged over an approximately 2-h time interval. The results show significant wind and temperature effects on black carbon concentration and composition in a way more complex than predicted by Gaussian dispersion models. Under oblique low winds, namely ux [= u * sin(g=q)]~ (0,-0.5 m s-1), which mostly occurred during morning hours, black carbon concentrations per unit traffic flow were highest and had large variation. The variability did not always follow Gaussian dispersion but was characteristic of a uniform distribution at a near-road distance. Under all other wind conditions, the near-road black carbon variation met Gaussian dispersion characteristics. Significant differences in roadside dispersion are observed between OC and EC fractions, between PM2.5 and PM10-2.5, and between the morning period and rest of the day. In a general case, the overall black carbon variability at the multi lane highway can be stated as bimodal consisting of Gaussian dispersion and non Gaussian uniform distribution. Transition between the two types depends on wind velocity and wind angle to the traffic flow. In the order of decreasing importance, the microclimatic controlling factors over the black carbon variability are: 1) wind velocity and the angle with traffic; 2) diurnal temperature variations due to thermal buoyancy; and 3) downwind Gaussian dispersion. Combinations of these factors may have created various traffic microclimate interactions that have significant impact on near-road black carbon transport. PMID- 26561362 TI - Molcas 8: New capabilities for multiconfigurational quantum chemical calculations across the periodic table. AB - In this report, we summarize and describe the recent unique updates and additions to the Molcas quantum chemistry program suite as contained in release version 8. These updates include natural and spin orbitals for studies of magnetic properties, local and linear scaling methods for the Douglas-Kroll-Hess transformation, the generalized active space concept in MCSCF methods, a combination of multiconfigurational wave functions with density functional theory in the MC-PDFT method, additional methods for computation of magnetic properties, methods for diabatization, analytical gradients of state average complete active space SCF in association with density fitting, methods for constrained fragment optimization, large-scale parallel multireference configuration interaction including analytic gradients via the interface to the Columbus package, and approximations of the CASPT2 method to be used for computations of large systems. In addition, the report includes the description of a computational machinery for nonlinear optical spectroscopy through an interface to the QM/MM package Cobramm. Further, a module to run molecular dynamics simulations is added, two surface hopping algorithms are included to enable nonadiabatic calculations, and the DQ method for diabatization is added. Finally, we report on the subject of improvements with respects to alternative file options and parallelization. PMID- 26561364 TI - Synthesis and in vitro cytotoxicity of novel C-12 substituted-14-deoxy andrographolide derivatives as potent anti-cancer agents. AB - Andrographolide, the major labdane diterpenoid from Andrographis paniculata has been reported to be cytotoxic against various cancer cells in vitro. Our research efforts led to the discovery of novel 12-phenyl thio and 12-aryl amino-14-deoxy andrographolide derivatives (III q and III r) with potent cytotoxic activity, 12 benzyl amino-14-deoxy-andrographolide analogues showing broad range of cytotoxic activity against most of the cell lines and 12-alkyl amino-14-deoxy andrographolide derivatives being selective to few cell lines (PC-3 and HOP-92), when the selected analogues were evaluated against 60 human cancer cell line panel at National Cancer Institute (N.C.I.), USA. The SAR (structure activity relationship) studies demonstrated potent activity for the compounds containing the following functionalities at C-12: substituted aryl amino/phenyl thio>benzylamine>alkyl amine. The significant cytotoxic activity observed for compounds III q and III r suggest that these could serve as templates for further optimization. PMID- 26561365 TI - Synthesis, in vitro, and in vivo evaluation of novel functionalized quaternary ammonium curcuminoids as potential anti-cancer agents. AB - Novel functionalized quaternary ammonium curcuminoids have been synthesized from piperazinyl curcuminoids and Baylis-Hillman reaction derived allyl bromides. These molecules are found to be highly water soluble with increased cytotoxicity compared to native curcumin against three cancer cell lines MIAPaCa-2, MDA-MB 231, and 4T1. Preliminary in vivo toxicity evaluation of a representative curcuminoid 5a in healthy mice indicates that this molecule is well tolerated based on normal body weight gains compared to control group. Furthermore, the efficacy of 5a has been tested in a pancreatic cancer xenograft model of MIAPaCa 2 and has been found to exhibit good tumor growth inhibition as a single agent and also in combination with clinical pancreatic cancer drug gemcitabine. PMID- 26561366 TI - Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells. AB - Activated B cells have the capacity to present antigen and induce immune responses as potent antigen-presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40-activated B cells (CD40Bs), as a model for activated, antigen-presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T-cell epitope 509-523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T-cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non-classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non-classical class II pathway. PMID- 26561367 TI - In alcoholic cirrhosis, low-serum hepcidin levels associate with poor long-term survival. AB - BACKGROUND & AIMS: Iron constitutes a potentially toxic element and consequently, hepatic iron overload may accelerate liver disease progression and development of hepatocellular carcinoma (HCC). Hepcidin is the central negative regulator of iron metabolism that is produced primarily by the liver. METHODS: To study the prognostic significance of serum hepcidin, we assessed the influence of baseline serum hepcidin levels on the outcome of a French cohort encompassing 237 patients with alcoholic cirrhosis prospectively followed up in the setting of HCC screening. RESULTS: Hepcidin values correlated weakly with serum ferritin levels (r = 0.33) and hepatic iron scores (r = 0.3). After a median follow-up of 68 months, patients with baseline lower hepcidin level had a higher risk of HCC occurrence [hazard ratio, HR = 1.76 (1.01-3.06), P = 0.031] and overall death [HR = 1.63 (1.07-2.44), P = 0.019]. According to Cox multivariate analyses, lower hepcidin levels were independently associated with death [HR = 2.84 (1.29-6.25), P = 0.009] along with higher Child-Pugh score while HCC occurrence was mainly associated with clinical confounders interfering with iron metabolism (older age and higher BMI, adjusted P-value for hepcidin = 0.119). CONCLUSIONS: In conclusion, low-serum hepcidin levels in patients with alcoholic cirrhosis bear a long-term prognostic significance warranting further explorations. PMID- 26561368 TI - Multichannel Ultrasonic Data Communications in Air Using Range-Dependent Modulation Schemes. AB - There are several well-developed technologies of wireless communication such as radio frequency (RF) and infrared (IR), but ultrasonic methods can be a good alternative in some situations. A multichannel airborne ultrasonic data communication system is described in this paper. ON-OFF keying (OOK) and binary phase-shift keying (BPSK) modulation schemes were implemented successfully in the system by using a pair of commercially available capacitive ultrasonic transducers in a relatively low multipath indoor laboratory environment. Six channels were used from 50 to 110 kHz with a channel spacing of 12 kHz, allowing multiple 8-bit data packets to be transmitted simultaneously. The system data transfer rate achieved was up to 60 kb/s and ultrasonic wireless synchronization was implemented instead of using a hard-wired link. A model developed in the work could accurately predict ultrasonic signals through the air channels. Signal root mean square (rms) values and system bit error rates (BERs) were analyzed over different distances. Error-free decoding was achieved over ranges up to 5 m using a multichannel OOK modulation scheme. To obtain the highest data transfer rate and the longest error-free transmission distance, a range-dependent multichannel scheme with variable data rates, channel frequencies, and different modulation schemes, was also studied in the work. Within 2 m, error-free transmission was achieved using a five-channel OOK with a data rate of 63 kb/s. Between 2 and 5 m, six-channel OOK with 60 kb/s data transfer rate was error free. Beyond 5 m, the error-free transmission range could be extended up to 10 m using three-channel BPSK with a reduced data rate of 30 kb/s. The situation when two transducers were misaligned using three-channel OOK and BPSK schemes was also investigated in the work. It was concluded that error-free transmission could still be achieved with a lateral displacement of less than 7% and oblique angles of less than 7 degrees , and three-channel BPSK proved to be more robust than three-channel OOK with transducer misalignment. PMID- 26561371 TI - Comorbid obsessive-compulsive disorder with bipolar disorder: A distinct form? AB - We examined whether the patients with Bipolar Disorder (BD) and Obsessive Compulsive Disorder (OCD) comorbidity may represent a distinct form of BD. The subjects diagnosed with BD (n=48), OCD (n=61), and BD with OCD (n=32) were compared in terms of several socio-demographic and clinical characteristics. Previous history of suicidal attempts was more likely to be higher in BD-OCD group compared to the other two groups. A more episodic course of OCD, higher rates of rapid cycling, and the seasonality were found in BD-OCD patients. The frequency of bipolar II and NOS subtypes was more prevalent in patients with BD OCD than in OCD patients. The first diagnosed illness was BD in the majority of BD-OCD cases. It was found that first affective episode was major depression in half of BD-OCD patients. Age at onset of BD was found to be earlier in BD-OCD group compared to pure BD patients. Bipolarity may not have a specific effect on the phenomenology of OC symptoms. The episodic course of OCD, seasonality, rapid cycling, earlier onset of BD, and impulsivity in BD-OCD patients may be indicative for a distinct form of BD. PMID- 26561370 TI - Alginate Microspheres Containing Temperature Sensitive Liposomes (TSL) for MR Guided Embolization and Triggered Release of Doxorubicin. AB - OBJECTIVE: The objective of this study was to develop and characterize alginate microspheres suitable for embolization with on-demand triggered doxorubicin (DOX) release and whereby the microspheres as well as the drug releasing process can be visualized in vivo using MRI. METHODS AND FINDINGS: For this purpose, barium crosslinked alginate microspheres were loaded with temperature sensitive liposomes (TSL/TSL-Ba-ms), which release their payload upon mild hyperthermia. These TSL contained DOX and [Gd(HPDO3A)(H2O)], a T1 MRI contrast agent, for real time visualization of the release. Empty alginate microspheres crosslinked with holmium ions (T2* MRI contrast agent, Ho-ms) were mixed with TSL-Ba-ms to allow microsphere visualization. TSL-Ba-ms and Ho-ms were prepared with a homemade spray device and sized by sieving. Encapsulation of TSL in barium crosslinked microspheres changed the triggered release properties only slightly: 95% of the loaded DOX was released from free TSL vs. 86% release for TSL-Ba-ms within 30 seconds in 50% FBS at 42 degrees C. TSL-Ba-ms (76 +/- 41 MUm) and Ho-ms (64 +/- 29 MUm) had a comparable size, which most likely will result in a similar in vivo tissue distribution after an i.v. co-injection and therefore Ho-ms can be used as tracer for the TSL-Ba-ms. MR imaging of a TSL-Ba-ms and Ho-ms mixture (ratio 95:5) before and after hyperthermia allowed in vitro and in vivo visualization of microsphere deposition (T2*-weighted images) as well as temperature-triggered release (T1-weighted images). The [Gd(HPDO3A)(H2O)] release and clusters of microspheres containing holmium ions were visualized in a VX2 tumor model in a rabbit using MRI. CONCLUSIONS: In conclusion, these TSL-Ba-ms and Ho-ms are promising systems for real-time, MR-guided embolization and triggered release of drugs in vivo. PMID- 26561372 TI - Spectral separation of optical spin based on antisymmetric Fano resonances. AB - We propose a route to the spectral separation of optical spin angular momentum based on spin-dependent Fano resonances with antisymmetric spectral profiles. By developing a spin-form coupled mode theory for chiral materials, the origin of antisymmetric Fano spectra is clarified in terms of the opposite temporal phase shift for each spin, which is the result of counter-rotating spin eigenvectors. An analytical expression of a spin-density Fano parameter is derived to enable quantitative analysis of the Fano-induced spin separation in the spectral domain. As an application, we demonstrate optical spin switching utilizing the extreme spectral sensitivity of the spin-density reversal. Our result paves a path toward the conservative spectral separation of spins without any need of the magneto optical effect or circular dichroism, achieving excellent purity in spin density superior to conventional approaches based on circular dichroism. PMID- 26561373 TI - Induction and Maintenance of Anti-HBs in Immunosuppressed Rats After Liver Transplantation with HBsAg-pulsed Dendritic Cell Complex. AB - BACKGROUND: This study aimed to investigate the efficacy of hepatitis B surface antigen (HBsAg)-pulsed dendritic cell (DC) complex in the induction and maintenance of anti-HBs in immunosuppressed rats after liver transplantation. MATERIAL AND METHODS: Lewis-Brown Norway (BN) rat liver transplantation models were successfully established. Recipients were injected with tacrolimus (2 mg/Kg) daily post-operation for three months to maintain immunosuppression state; the recipients were then randomly divided into two groups: HBsAg-DC group (n=15) comprised rats intraperitoneally injected with HBsAg-DC complex at 14 and 28 d post-surgery and HBsAg group (n=15) comprised rats injected with HBsAg (200 MUL) once a week for 12 weeks. Untreated rats post-transplantation were included in the control group (n=5). Histopathological changes were detected by light microscopy and transmission electron microscopy; mRNA expressions of IL-2 and IFN gamma in graft liver were analyzed through real-time polymerase chain reaction. Serum IL-2 and IFN-gamma levels and anti-HB titer were detected through enzyme linked immunosorbent assay. Changes in CD4+ and CD8+ T cells in the blood were detected through flow cytometry. RESULTS: IL-2 and IFN-gamma expressions were lower in HBsAg-DC and HBsAg groups than in the control group (P<0.05). A high FK506 dose also induced a milder allograft rejection than the control dose. These findings showed that a high FK506 dose caused immunosuppression in rats after liver transplantation. A high anti-HB titer was detected in the HBsAg-DC group in one, two, and three months post-operation; by contrast, anti-HB titer was barely detected in the HBsAg group. CONCLUSIONS: High anti-HB titers could be induced and maintained in immunosuppressed rats; therefore, HBsAg-DC complex may prevent HBV reinfection after recipients undergo liver transplantation. PMID- 26561374 TI - The Feasibility and Safety of Adopting Single-Incision Laparoscopic Surgery into Gynecologic Oncology Practice. AB - STUDY OBJECTIVE: To determine the complications associated with single-incision laparoscopy in gynecologic oncology surgery. DESIGN: A retrospective cohort (Canadian Task Force classification II-3). SETTING: A single academic institution. PATIENTS: One hundred fifteen consecutive patients undergoing single incision laparoscopy with suspected gynecologic oncology conditions. INTERVENTIONS: Single-incision laparoscopy. MEASUREMENTS AND MAIN RESULTS: One hundred fifteen patients underwent single-incision laparoscopy. The mean age was 55.3 +/- 13.1 years. For procedures completed via single-incision laparoscopy (102/115 [88.7%]), the mean operative time was 130.7 +/- 55.5 minutes. The average blood loss was 63 +/- 111 mL. The conversion to open rate was 13 of 115 (12.17%). The conversion rate of the 55 patients with benign conditions was lower (2/55 [3.64%]) compared with the 60 patients with malignant conditions (11/60 [18.33%]). The hernia rate was 2 of 115 (1.80%), 1 of which was a recurrent hernia. The median time for follow-up was 30 days (range, 5-653 days). CONCLUSION: Single-incision laparoscopy provides a feasible, safe, and promising minimally invasive modality for treating gynecologic oncology patients. PMID- 26561375 TI - Multi-steps green process for synthesis of six-membered functional cyclic carbonate from trimethylolpropane by lipase catalyzed methacrylation and carbonation, and thermal cyclization. AB - A highly functionalized six-membered cyclic carbonate, methacrylated trimethylolpropane (TMP) cyclic carbonate, which can be used as a potential monomer for bisphenol-free polycarbonates and isocyanate-free polyurethanes, was synthesized by two steps transesterifications catalyzed by immobilized Candida antarctica lipase B, Novozym((r)) 435 (N435) followed by thermal cyclization. TMP was functionalized as 70 to 80% selectivity of mono-methacrylate with 70% conversion was achieved, and the reaction rate was evaluated using various acyl donors such as methacrylic acid, methacrylate-methyl ester, -ethyl ester, and vinyl ester. As a new observation, the fastest rate obtained was for the transesterfication reaction using methacrylate methyl ester. Byproducts resulted from leaving groups were adsorbed on the molecular sieves (4A) to minimize the effect of leaving group on the equilibrium. The difference of reaction rate was explained by molecular dynamic simulations on interactions between carbonyl oxygen and amino acid residues (Thr 40 and Glu 157) in the active site of lipase. Our docking studies revealed that as acyl donor, methyl ester was preferred for the initial conformation of the first tetrahederal intermediate with hydrogen bonding interactions. TMP-monomethacrylate (TMP-mMA) cyclic carbonate was obtained in 63% yield (74.1% calculated in 85% conversion) from the lipase catalyzed carbonation reaction of TMP-mMA with dimethylcarbonate, and followed by thermal cyclization of the monocarbonate at 90 degrees C. From the multiple reactions demonstrated in gram scale, TMP-mMA cyclic carbonate was obtained as a green process without using chlorinated solvent and reagent. PMID- 26561376 TI - Virtual reality exposure using three-dimensional images for the treatment of social phobia. AB - OBJECTIVE: To test a potential treatment for social phobia, which provides exposure to phobia-inducing situations via computer-generated, three-dimensional images, using an open clinical trial design. METHODS: Twenty-one patients with a DSM-IV diagnosis of social phobia took part in the trial. Treatment consisted of up to 12 sessions of exposure to relevant images, each session lasting 50 minutes. RESULTS: Improvements in social anxiety were seen in all scales and instruments used, including at follow-up 6 months after the end of treatment. The average number of sessions was seven, as the participants habituated rapidly to the process. Only one participant dropped out. CONCLUSION: This study provides evidence that exposure to computer-generated three-dimensional images is relatively inexpensive, leads to greater treatment adherence, and can reduce social anxiety. Further studies are needed to corroborate these findings. PMID- 26561377 TI - Co-occurrence of communication disorder and psychiatric disorders in maltreated children and adolescents: relationship with global functioning. AB - OBJECTIVE: To study the co-occurrence of psychiatric disorders (PD) and communication disorders (CD) and their relationship with global functioning in maltreated children and adolescents. METHODS: The sample comprised 143 maltreated children and adolescents (55.8% male). All underwent clinical communication and psychiatric evaluations, as well as global functioning assessment using the Children's Global Assessment Scale (C-GAS). RESULTS: Four groups emerged from evaluation: Group 1 (n=7, 4.9%) did not exhibit any disorders; Group 2 (n=26, 18.2%) exhibited PD; Group 3 (n=34, 23.8%) exhibited CD; and Group 4 (n=76, 53.1%) exhibited both PD and CD on evaluation. Significant differences in global functioning scores were found between G1 and G2, G1 and G4, G2 and G4, and G3 and G4, with the highest C-GAS scores found in G1 and the lowest in G4. CONCLUSION: Rates of PD and CD are high in this maltreated population. The presence of PD has a major impact on C-GAS score, and the simultaneous presence of CD increases the already impaired function of PD. Demonstration of the additive effects of PD and CD on youth functioning suggests that professionals should be alert to the presence of both disorders to better act preventively and therapeutically in a high-risk population. PMID- 26561378 TI - Survival, Hospitalization, and Acute-Care Costs of Very and Moderate Preterm Infants in the First 6 Years of Life: A Population-Based Study. AB - OBJECTIVES: To investigate survival, hospitalization, and acute-care costs of very (28-31 weeks' gestation) and moderate preterm (32-33 weeks' gestation) infants in the first 6 years of life and compare outcomes with the more widely studied extremely preterm infants (24-27 weeks' gestation) and to full term (low risk) infants (39-40 weeks' gestation). STUDY DESIGN: Birth data from all women residing in New South Wales, Australia, with gestational ages between 24-33 and 39-40 weeks in 2001-2011 were linked probabilistically to hospitalization and mortality data. Study outcomes were evaluated with the use of descriptive and multivariable analyses at birth (N = 559,532), discharge (N = 540,240), and at 1 (N = 487,447) and 6 years of age (N = 230,498). RESULTS: Mortality was greatest among extremely preterm infants (eg, 31.2% within 6 years) and decreased with increasing gestational age. Likewise, hospitalization within the first year of life increased with decreasing gestational age (aOR 5.5 [95% CI 4.7-6.4], 3.7 [3.4-4.0], and 2.6 [2.5-2.8] for birth at 24-27, 28-31, and 32-33 weeks' gestation, relative to 39-40 weeks' gestation). Hospitalization remained significantly increased with preterm birth at each year of age up to 6 years (aORs 1.3-1.6 at 6 years). Cumulative costs were significantly greater with preterm birth within the first year of life, and also between 1 and 6 years of age. CONCLUSIONS: The risks of adverse health outcomes were significantly greater in very and moderately preterm infants relative to full term infants but lower than extremely preterm infants. Crucially, preterm birth was associated with prolonged increased odds of hospitalization (up to age 6 years), contributing to greater resource use. PMID- 26561379 TI - Prescription Use among Children with Autism Spectrum Disorders in Northern New England: Intensity and Small Area Variation. AB - OBJECTIVE: To measure prescription use intensity and regional variation of psychotropic and 2 important nonpsychotropic drug groups among children with autism spectrum disorders (ASDs) compared with children in the general population. STUDY DESIGN: Cross-sectional study of ambulatory prescription fills from Maine, Vermont, and New Hampshire all-payer administrative data, 2007-2010. RESULTS: Overall there were 13,100 children diagnosed with ASD (34,584 person years [PYs]) and 936,721 (1.7 million PYs) without ASD diagnosis. The overall prescription fill rate was 16.6 per PY in children with ASD and 4.1 per PY in the general population. Psychotropic use among children with ASDs was 9-fold the general population rate (7.80 vs 0.85 fills per PY); these children comprised 2.0% of the pediatric population but received 15.6% of psychotropics. Nonpsychotropic drug use was also higher in the population with ASD, particularly the youngest: among those under age 3 years, antibiotic use was 2-fold and antacid use nearly 5-fold the general population rate (3.2 vs 1.4 and 1.0 vs 0.2 per PY, respectively). Among children with ASDs, prescription use varied substantially across hospital service areas, as much as 3-fold for antacids and alpha agonists, more than 4-fold for benzodiazepines (5th to 95th percentile). CONCLUSIONS: The overall psychotropic and nonpsychotropic prescription intensity among children with ASDs is characterized by broad regional variation, suggesting diverse provider responses to pharmacotherapeutic uncertainty. This variation highlights a need for more research, practice-based learning, and shared decision making with caregivers surrounding therapy for children with ASDs. PMID- 26561380 TI - Global and Regional Derangements of Cerebral Blood Flow and Diffusion Magnetic Resonance Imaging after Pediatric Cardiac Arrest. AB - OBJECTIVE: To quantify and examine the relationship between global and regional cerebral blood flow (CBF) and water diffusion on brain magnetic resonance imaging (MRI) in children after cardiac arrest. STUDY DESIGN: Children admitted to a tertiary care children's hospital from July 2011 to April 2013 who received a brain MRI within 2 weeks after cardiac arrest that included arterial spin labeling and apparent diffusion coefficient (ADC) sequences were studied. CBF and ADC values were calculated globally and in 19 regions of interest. Outcome variables included survival and favorable neurologic outcome, which was defined as Pediatric Cerebral Performance Category <=3 at 6 months. We examined global and regional relationships between CBF and ADC and their association with outcome. RESULTS: This sample included 14 pediatric patients (mean time to MRI 6 +/- 4 days), 9 of whom survived and 6 who survived with favorable outcome. Global ADC was significantly decreased in patients with unfavorable outcome (P = .02). Increased CBF and decreased ADC often were colocalized in the same region, especially in children who had unfavorable outcomes. CONCLUSIONS: In this exploratory study, global restricted water diffusion on ADC after pediatric cardiac arrest was associated with unfavorable outcome. MRI assessments of perfusion and diffusion may have prognostic value after pediatric cardiac arrest. PMID- 26561381 TI - Reduced Bone Mineral Density Is Associated with Celiac Disease Autoimmunity in Children with Type 1 Diabetes. AB - OBJECTIVE: To evaluate the association between bone mineral density (BMD), glycemic control (hemoglobin A1c [HbA1c]), and celiac autoimmunity in children with type 1 diabetes mellitus (T1D) and in an appropriate control population. STUDY DESIGN: BMD was assessed cross-sectionally in 252 children with T1D (123 positive for anti-tissue transglutaminase antibody [tTGA] and 129 matched children who were negative for tTGA). In addition, BMD was assessed in 141 children without diabetes who carried T1D-associated HLD-DR, DQ genotypes (71 positive for tTGA and 70 negative). RESULTS: Children with T1D who were positive for tTGA had significantly worse BMD L1-L4 z-score compared with children with T1D who were negative for tTGA (-0.45 +/- 1.22 vs 0.09 +/- 1.10, P = .0003). No differences in growth measures, urine N-telopeptides, 25-hydroxyvitamin D, ferritin, thyroid stimulating hormone, or HbA1c were found. However, both higher HbA1c (beta = -1.25 +/- 0.85, P = .0016) and tTGA (beta = -0.13 +/- 0.05, P = .0056) were significant and independent predictors of lower BMD in multivariate analyses. No differences in BMD or other variables measured were found between children without diabetes who were positive vs negative for tTGA. CONCLUSIONS: The results suggest a synergistic effect of hyperglycemia and celiac autoimmunity on low BMD. PMID- 26561382 TI - Estimates of the energy deficit required to reverse the trend in childhood obesity in Australian schoolchildren. AB - OBJECTIVES: To estimate: 1) daily energy deficit required to reduce the weight of overweight children to within normal range; 2) time required to reach normal weight for a proposed achievable (small) target energy deficit of 0.42 MJ/day; 3) impact that such an effect may have on prevalence of childhood overweight. METHODS: Body mass index and fitness were measured in 31,424 Australian school children aged between 4.5 and 15 years. The daily energy deficit required to reduce weight to within normal range for the 7,747 (24.7%) overweight children was estimated. Further, for a proposed achievable target energy deficit of 0.42 MJ/day, the time required to reach normal weight was estimated. RESULTS: About 18% of children were overweight and 6.6% obese; 69% were either sedentary or light active. If an energy deficit of 0.42 MJ/day could be achieved, 60% of overweight children would reach normal weight and the current prevalence of overweight of 24.7% (24.2%-25.1%) would be reduced to 9.2% (8.9%-9.6%) within about 15 months. CONCLUSIONS: The prevalence of overweight in Australian school children could be reduced significantly within one year if even a small daily energy deficit could be achieved by children currently classified as overweight or obese. PMID- 26561383 TI - Yb3+/Er3+-Codoped Bi2O3 Nanospheres: Probe for Upconversion Luminescence Imaging and Binary Contrast Agent for Computed Tomography Imaging. AB - In this work, water-soluble Yb(3+)/Er(3+) codoped Bi2O3 upconversion (UC) nanospheres with uniform morphology have been successfully synthesized via a solid-state-chemistry thermal decomposition process. With 980 nm near-infrared irradiation, the Bi2O3:Yb(3+)/Er(3+) nanospheres have bright UC luminescence (UCL). Moreover, multicolor UC emissions (from green to red) can be tuned by simply changing the Yb(3+) ions doping concentration. After citric acid molecules were grafted on the surface of Bi2O3:20% Yb(3+)/2% Er(3+) nanospheres, the MTT assay on HeLa cells and CCK-8 assay on osteoblasts show that the UC nanospheres exhibit excellent stability and biocompatibility. The possibility of using these nanoprobes with red UCL for optical imaging in vivo has been demonstrated. Furthermore, Bi(3+) and Yb(3+) containing nanospheres as binary contrast agent also exhibited significant enhancement of contrast efficacy than iodine-based contrast agent via X-ray computed tomography (CT) imaging at different voltage setting (80-140 kVp), indicating they have potential as CT imaging contrast agent. Thus, Yb(3+)/Er(3+) codoped Bi2O3 nanospheres could be used as dual modality probe for optical and CT imagings. PMID- 26561384 TI - ActicoatTM stimulates inflammation, but does not delay healing, in acute full thickness excisional wounds. AB - ActicoatTM has antimicrobial and anti-inflammatory effects which aid wound healing. However, in vitro studies indicate that ActicoatTM is cytotoxic and clinical and in vivo studies suggest that it may delay healing in acute wounds. Therefore, this study investigated the effects of ActicoatTM on healing in acute full-thickness excisional wounds. Using a porcine model, healing was assessed on days 3, 6, 9 and 15 post-wounding. Five wounds dressed with ActicoatTM and five wounds dressed with polyurethane film (control) were assessed per day (n = 40 wounds). The rate of healing, inflammatory response, restoration of the epithelium and blood vessel and collagen formation were evaluated. No difference was found in the rate of healing between wounds treated with ActicoatTM and the control wounds. Inflammation was increased in ActicoatTM-treated wounds on day 3 post-wounding compared to the control wounds. However, by day 15 post-wounding, the epithelium of the ActicoatTM-treated wounds closely resembled normal epithelium. ActicoatTM-treated wounds also contained a higher proportion of mature blood vessels, and differences in collagen deposition were apparent. Despite inducing an inflammatory response, ActicoatTM did not delay healing in acute wounds. Conversely, the improved quality of the epithelium and blood vessels within ActicoatTM-treated wounds indicates that ActicoatTM has a beneficial effect on healing. PMID- 26561385 TI - Enhancing Hematite Photoanode Activity for Water Oxidation by Incorporation of Reduced Graphene Oxide. AB - Two effective methods to prepare reduced graphene oxide (rGO)/hematite nanostructured photoanodes and their photoelectrochemical characterization towards water splitting reactions are presented. First, graphene oxide (GO) is reduced to rGO using hydrazine in a basic solution containing tetrabutylammonium hydroxide (TBAOH), and then deposited over the nanostructured hematite photoanodes previously treated at 750 degrees C for 30 min. The second method follows the deposition of a paste containing a mixture of hematite nanoparticles and rGO sheets by the doctor-blade method, varying the rGO concentration. Since hematite suffers from low electron mobility, a low absorption coefficient, high recombination rates and slow reaction kinetics, the incorporation of rGO in the hematite can overcome such limitations due to graphene's exceptional properties. Using the first method, the rGO incorporation results in a photocurrent density increase from 0.56 to 0.82 mA cm(-2) at 1.23 VRHE. Our results indicate that the rGO incorporation in the hematite photoanodes shows a positive effect in the reduction of the electron-hole recombination rate. PMID- 26561386 TI - Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs. AB - Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis, while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and delay gut bacterial colonization and thereby protect preterm neonates against both NEC and bacteremia in the immediate postnatal period. Preterm pigs were given formula and administered saline (CON) or broad-spectrum antibiotics orally (ORA) or systemically (SYS) for 5 d after birth. Temporal changes in blood parameters and bacterial composition in the intestine, blood and immune organs were analyzed. Newborn preterm pigs had few blood neutrophils and a high frequency of progenitor cells. Neutrophils gradually matured after preterm birth with increasing CD14 and decreasing CD172a expressions. Preterm neutrophil and monocyte TLR2 expression and TLR2-mediated blood cytokine responses were low relative to adults. ORA pigs showed enhanced blood neutrophil maturation with reduced cell size and CD172a expression. Only ORA pigs, but not SYS pigs, were protected from a high density of gut Gram-positive bacteria, high gut permeability, Gram-positive bacteremia and NEC. Neonatal oral antibiotics may benefit mucosal and systemic immunity via delayed gut colonization and enhanced blood neutrophil maturation just after preterm birth. PMID- 26561387 TI - Electronic Health Record Adoption In US Hospitals: Progress Continues, But Challenges Persist. AB - Achieving nationwide adoption of electronic health records (EHRs) remains an important policy priority. While EHR adoption has increased steadily since 2010, it is unclear how providers that have not yet adopted will fare now that federal incentives have converted to penalties. We used 2008-14 national data, which includes the most recently available, to examine hospital EHR trends. We found large gains in adoption, with 75 percent of US hospitals now having adopted at least a basic EHR system--up from 59 percent in 2013. However, small and rural hospitals continue to lag behind. Among hospitals without a basic EHR system, the function most often not yet adopted (in 61 percent of hospitals) was physician notes. We also saw large increases in the ability to meet core stage 2 meaningful use criteria (40.5 percent of hospitals, up from 5.8 percent in 2013); much of this progress resulted from increased ability to meet criteria related to exchange of health information with patients and with other physicians during care transitions. Finally, hospitals most often reported up-front and ongoing costs, physician cooperation, and complexity of meeting meaningful-use criteria as challenges. Our findings suggest that nationwide hospital EHR adoption is in reach but will require attention to small and rural hospitals and strategies to address financial challenges, particularly now that penalties for lack of adoption have begun. PMID- 26561388 TI - X-ray photoemission analysis of clean and carbon monoxide-chemisorbed platinum(111) stepped surfaces using a curved crystal. AB - Surface chemistry and catalysis studies could significantly gain from the systematic variation of surface active sites, tested under the very same conditions. Curved crystals are excellent platforms to perform such systematics, which may in turn allow to better resolve fundamental properties and reveal new phenomena. This is demonstrated here for the carbon monoxide/platinum system. We curve a platinum crystal around the high-symmetry (111) direction and carry out photoemission scans on top. This renders the spatial core-level imaging of carbon monoxide adsorbed on a 'tunable' vicinal surface, allowing a straightforward visualization of the rich chemisorption phenomenology at steps and terraces. Through such photoemission images we probe a characteristic elastic strain variation at stepped surfaces, and unveil subtle stress-release effects on clean and covered vicinal surfaces. These results offer the prospect of applying the curved surface approach to rationally investigate the chemical activity of surfaces under real pressure conditions. PMID- 26561389 TI - Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis. AB - Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection. PMID- 26561390 TI - Persistence of Antibody to Influenza A/H5N1 Vaccine Virus: Impact of AS03 Adjuvant. AB - The adjuvant AS03 is stockpiled for future formulations with new and existing vaccines for the control of pandemic influenza virus. We previously reported the immunogenicity of an A/H5N1 vaccine extemporaneously mixed with the AS03 adjuvant for 42 days following vaccination. This report extends those findings to 1 year after vaccination. PMID- 26561391 TI - Cerebral salt wasting after traumatic brain injury: a review of the literature. AB - Electrolyte imbalances are common among patients with traumatic brain injury (TBI). Cerebral salt wasting (CSW) is an electrolyte imbalance characterized by hyponatremia and hypovolemia. Differentiating the syndrome of inappropriate antidiuretic hormone and CSW remains difficult and the pathophysiological mechanisms underlying CSW are unclear. Our intent was to review the literature on CSW within the TBI population, in order to report the incidence and timing of CSW after TBI, examine outcomes, and summarize the biochemical changes in patients who developed CSW. We searched MEDLINE through 2014, hand-reviewed citations, and searched abstracts from the American Association for the Surgery of Trauma (2003 2014). Publications were included if they were conducted within a TBI population, presented original data, and diagnosed CSW. Publications were excluded if they were review articles, discussed hyponatremia but did not differentiate the etiology causing hyponatremia, or presented cases with chronic disease. Fifteen of the 47 publications reviewed met the selection criteria; nine (60%) were case reports, five (33%) were prospective and 1 (7%) was a retrospective study. Incidence of CSW varied between 0.8 - 34.6%. The populations studied were heterogeneous and the criteria used to define hyponatremia and CSW varied. Though believed to play a role in the development of CSW, increased levels of natriuretic peptides in patients diagnosed with CSW were not consistently reported. These findings reinforce the elusiveness of the CSW diagnosis and the need for strict and consistent diagnostic criteria. PMID- 26561392 TI - Dynamic Change of CD34 Level during the Survival Process of Narrow Pedicle Flap. AB - OBJECTIVE: To evaluate the dynamic change of CD34 level during the survival process of narrow pedicle flaps. METHODS: Twenty-five white pigs were randomly and equally divided into 5 experimental groups. Five different type of narrow pedicle with different length-to-width ratio were employed, and each type of narrow pedicle was covered with 5 different size random flaps and which was classified into A, B, C, D and E for 5 groups. Group A was control group. Each type narrow pedicle with 5 different skin flaps were implanted onto the back of the pigs along the midline of back with a reverse direction. A 0.3 cm*0.3 cm full thickness skin flap in the middle of distal segment was collected and on 3rd, 5th, 7th and 14th days of post-operation. The expression of CD34 was measured by immunohistochemistry and enzyme-linked immunosorbent (ELISA). RESULTS: Histological examination showed that with the increasing of length-to-width ratio of the narrow pedicle skin flaps, the expression of CD34 increased in the skin flaps. Increased level of CD34 was found on 3rd day post-operation, and the peak expression was found on 7th day. Persistent high level of CD34 was found until 14th day. CONCLUSION: Increased CD34 level in the distal skin flap, there is the association between CD34 level and ischemia injury. Moreover, CD34 expression plays an important role during the repair processes of pedicle flaps. PMID- 26561395 TI - What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms? AB - Lung neuroendocrine tumors (NET) are currently classified in resection specimens according to four histological categories, namely typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCC). Diagnostic criteria have remained unchanged in the 2015 WHO classification, which has ratified the wide acceptance and popularity of such terminology in the pathologists' and clinicians' community. A unifying umbrella of NE morphology and differentiation has been recognized in lung NET, which has pushed to enter an unique box of invasive tumors along with diffuse idiopathic pulmonary NE cell hyperplasia (DIPNECH) as a pre-invasive lesion with a potential toward the development of carcinoids. However, uncertainties remain in the terminology of lung NET upon small samples, where Ki-67 antigen could play some role to avoid misdiagnosing carcinoids as high-grade NE tumors. Epidemiologic, clinical and genetic traits support a biological three-tier over a pathology four tier model, according to which TC are low malignancy tumors, AC intermediate malignancy tumors and LCNEC/SCC high malignancy tumors with no significant differences in survival among them. Inconsistencies in diagnostic reproducibility, troubles in the therapy of AC and LCNEC, and limitations to histology within the same tumor category argue in favor of a global re-thinking of lung NET where a grading system could play a role. This review outlines three main key questions in the field of lung NET: (A) unbiased diagnoses, (B) the role of Ki-67 and tumor grading, and (C) management of predictive markers. Answers are still inconclusive, thus additional research is required to improve our understanding on lung NET. PMID- 26561394 TI - RNA Sequencing Revealed Numerous Polyketide Synthase Genes in the Harmful Dinoflagellate Karenia mikimotoi. AB - The dinoflagellate Karenia mikimotoi forms blooms in the coastal waters of temperate regions and occasionally causes massive fish and invertebrate mortality. This study aimed to elucidate the toxic effect of K. mikimotoi on marine organisms by using the genomics approach; RNA-sequence libraries were constructed, and data were analyzed to identify toxin-related genes. Next generation sequencing produced 153,406 transcript contigs from the axenic culture of K. mikimotoi. BLASTX analysis against all assembled contigs revealed that 208 contigs were polyketide synthase (PKS) sequences. Thus, K. mikimotoi was thought to have several genes encoding PKS metabolites and to likely produce toxin-like polyketide molecules. Of all the sequences, approximately 30 encoded eight PKS genes, which were remarkably similar to those of Karenia brevis. Our phylogenetic analyses showed that these genes belonged to a new group of PKS type-I genes. Phylogenetic and active domain analyses showed that the amino acid sequence of four among eight Karenia PKS genes was not similar to any of the reported PKS genes. These PKS genes might possibly be associated with the synthesis of polyketide toxins produced by Karenia species. Further, a homology search revealed 10 contigs that were similar to a toxin gene responsible for the synthesis of saxitoxin (sxtA) in the toxic dinoflagellate Alexandrium fundyense. These contigs encoded A1-A3 domains of sxtA genes. Thus, this study identified some transcripts in K. mikimotoi that might be associated with several putative toxin-related genes. The findings of this study might help understand the mechanism of toxicity of K. mikimotoi and other dinoflagellates. PMID- 26561393 TI - Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts. AB - Orofacial clefts (OFCs) represent a large fraction of human birth defects and are one of the most common phenotypes affected by large copy number variants (CNVs). Due to the limited number of CNV patients in individual centers, CNV analyses of a large number of OFC patients are challenging. The present study analyzed 249 genomic deletions and 226 duplications from a cohort of 312 OFC patients reported in two publicly accessible databases of chromosome imbalance and phenotype in humans, DECIPHER and ECARUCA. Genomic regions deleted or duplicated in multiple patients were identified, and genes in these overlapping CNVs were prioritized based on the number of genes encompassed by the region and gene expression in embryonic mouse palate. Our analyses of these overlapping CNVs identified two genes known to be causative for human OFCs, SATB2 and MEIS2, and 12 genes (DGCR6, FGF2, FRZB, LETM1, MAPK3, SPRY1, THBS1, TSHZ1, TTC28, TULP4, WHSC1, WHSC2) that are associated with OFC or orofacial development. Additionally, we report 34 deleted and 24 duplicated genes that have not previously been associated with OFCs but are associated with the BMP, MAPK and RAC1 pathways. Statistical analyses show that the high number of overlapping CNVs is not due to random occurrence. The identified genes are not located in highly variable genomic regions in healthy populations and are significantly enriched for genes that are involved in orofacial development. In summary, we report a CNV analysis pipeline of a large cohort of OFC patients and identify novel candidate OFC genes. PMID- 26561396 TI - Using Next Generation RAD Sequencing to Isolate Multispecies Microsatellites for Pilosocereus (Cactaceae). AB - Microsatellite markers (also known as SSRs, Simple Sequence Repeats) are widely used in plant science and are among the most informative molecular markers for population genetic investigations, but the development of such markers presents substantial challenges. In this report, we discuss how next generation sequencing can replace the cloning, Sanger sequencing, identification of polymorphic loci, and testing cross-amplification that were previously required to develop microsatellites. We report the development of a large set of microsatellite markers for five species of the Neotropical cactus genus Pilosocereus using a restriction-site-associated DNA sequencing (RAD-seq) on a Roche 454 platform. We identified an average of 165 microsatellites per individual, with the absolute numbers across individuals proportional to the sequence reads obtained per individual. Frequency distribution of the repeat units was similar in the five species, with shorter motifs such as di- and trinucleotide being the most abundant repeats. In addition, we provide 72 microsatellites that could be potentially amplified in the sampled species and 22 polymorphic microsatellites validated in two populations of the species Pilosocereus machrisii. Although low coverage sequencing among individuals was observed for most of the loci, which we suggest to be more related to the nature of the microsatellite markers and the possible bias inserted by the restriction enzymes than to the genome size, our work demonstrates that an NGS approach is an efficient method to isolate multispecies microsatellites even in non-model organisms. PMID- 26561397 TI - Incidence and predictors of interstitial lung disease (ILD) in Thai patients with early systemic sclerosis: Inception cohort study. AB - OBJECTIVES: To determine and compare the prevalence of interstitial lung disease (ILD), the severity of high-resolution computed tomography (HRCT) score and incidence rate (IR) of ILD between the two subsets of early-SSc (systemic sclerosis) patients. We also determined the factors associated with ILD. METHODS: We used an inception cohort of early-SSc patients seen between January 2010 and June 2014. All patients underwent HRCT at study entry and annually thereafter. RESULTS: One hundred and thirteen patients (66 females and 89 diffuse cutaneous SSc [dcSSc]) with a mean +/- SD age of 53.4 +/- 8.4 years and mean disease duration of 12.9 +/- 10.3 months at cohort entry were enrolled. At enrollment, patients with dcSSc had a higher prevalence of ILD (78.7% vs. 45.8%, p = 0.002), and a higher total HRCT score (10.3 +/- 9.5 vs. 4.4 +/- 5.6, p = 0.001) compared with limited cutaneous SSc (lcSSc). DcSSc patients had a higher IR of ILD than lcSSc patients (58.8 vs.17.3 per 100 person-years, p < 0.001). Univariable analysis revealed that male gender, presence of anti-Scl 70 and absent anti centromere antibody was significant predictors of ILD. In Cox-regression analysis, a positive anti-centromere [hazard ratio (HR) 0.09 95% confidence interval (95% CI 0.01-0.73)] was a protective factor. CONCLUSIONS: DcSSc patients had more severe HRCT scores and higher IR of ILD compared with lcSSc patients. Male gender, presence of anti-Scl 70, and absent anti-centromere antibody predicted the future development of ILD in early-SSc patients. PMID- 26561398 TI - Child mental health and maternal depression history in Pakistan. AB - PURPOSE: We address the significant gaps in knowledge of prevalence and correlates of child mental health (CMH) problems outside of high income countries. We describe the prevalence of CMH problems and their correlates with a focus on the association with maternal depression in a sample of seven-year-old children in rural Pakistan. METHODS: This study was nested in a long-term follow up of a perinatal depression intervention together with a reference group of non depressed women, yielding a population representative sample. The Total Difficulties (TD) and component scores of the Strength and Difficulties Questionnaire (SDQ) were used to measure emotional and behavioral difficulties. RESULTS: The mean SDQ TD score was 10.6 (standard deviation = 8.3), with 12.5 % of children categorized as "abnormal" using standard cutoffs. Boys had a roughly 1 point higher (worse) SDQ TD score than girls (p value = 0.04). Children of mothers who were depressed prenatally as well as currently had SDQ TD scores 2.87 points higher than children whose mothers were not depressed at either time point (p value < 0.01). This association was stronger for boys. There was no evidence of elevated SDQ TD score among children whose mothers were depressed only prenatally or only currently. Some deviations from this pattern were observed with specific components of the SDQ. CONCLUSIONS: In this low resource, South Asian setting, we found evidence of elevated levels of emotional and behavioral problems, highlighting the need for effective interventions. Given the strong association of CMH with maternal depression, any intervention efforts should give strong consideration to maternal mental health. PMID- 26561399 TI - P2Y12 receptor blockade synergizes strongly with nitric oxide and prostacyclin to inhibit platelet activation. AB - AIMS: In vivo platelet function is a product of intrinsic platelet reactivity, modifiable by dual antiplatelet therapy (DAPT), and the extrinsic inhibitory endothelial mediators, nitric oxide (NO) and prostacyclin (PGI2 ), that are powerfully potentiated by P2Y12 receptor blockade. This implies that for individual patients endothelial mediator production is an important determinant of DAPT effectiveness. Here, we have investigated this idea using platelets taken from healthy volunteers treated with anti-platelet drugs. METHODS: Three groups of male volunteers (n = 8) received either prasugrel (10 mg), aspirin (75 mg) or DAPT (prasugrel + aspirin) once daily for 7 days. Platelet reactivity in the presence of diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NONOate) and PGI2 was studied before and following treatment. RESULTS: Ex vivo, PGI2 and/or DEA/NONOate had little inhibitory effect on TRAP-6-induced platelet reactivity in control conditions. However, in the presence of DAPT, combination of DEA/NONOate + PGI2 reduced platelet aggregation (74 +/- 3% to 19 +/- 6%, P < 0.05). In vitro studies showed even partial (25%) P2Y12 receptor blockade produced a significant (67 +/- 2% to 39 +/- 10%, P < 0.05) inhibition when DEA/NONOate + PGI2 was present. CONCLUSIONS: We have demonstrated that PGI2 and NO synergize with P2Y12 receptor antagonists to produce powerful platelet inhibition. Furthermore, even with submaximal P2Y12 blockade the presence of PGI2 and NO greatly enhances platelet inhibition. Our findings highlight the importance of endothelial mediator in vivo modulation of P2Y12 inhibition and introduces the concept of refining ex vivo platelet function testing by incorporating an assessment of endothelial function to predict thrombotic outcomes better and adjust therapy to prevent adverse outcomes in individual patients. PMID- 26561400 TI - Association of Symptom Network Structure With the Course of [corrected] Depression. AB - IMPORTANCE: Major depressive disorder (MDD) is a heterogeneous condition in terms of symptoms, course, and underlying disease mechanisms. Current classifications do not adequately address this complexity. In novel network approaches to psychopathology, psychiatric disorders are conceptualized as complex dynamic systems of mutually interacting symptoms. This perspective implies that a more densely connected network of symptoms is indicative of a poorer prognosis, but, to date, no previous study has examined whether network structure is indeed associated with the longitudinal course of MDD. OBJECTIVE: To examine whether the baseline network structure of MDD symptoms is associated with the longitudinal course of MDD. DESIGN, SETTING, AND PARTICIPANTS: In this prospective study, in which remittent and persistent MDD was defined on the basis of a follow-up assessment after 2 years, 515 patients from the Netherlands Study of Depression and Anxiety with past-year MDD (established with the Composite International Diagnostic Interview) and at least moderate depressive symptoms (assessed with the Inventory of Depressive Symptomatology [IDS]) at baseline were studied. Baseline starting and ending dates were September 1, 2004, through February 28, 2007. Follow-up starting and ending dates were September 1, 2006, through February 28, 2009. Analysis was conducted August 2015. The MDD was considered persistent if patients had at least moderate depressive symptoms (IDS) at 2-year follow-up; otherwise, the MDD was considered remitted. MAIN OUTCOMES AND MEASURES: Sparse network structures of baseline MDD symptoms assessed via IDS were computed. Global and local connectivity of network structures were compared across persisters and remitters using a permutation test. RESULTS: Among the 515 patients, 335 (65.1%) were female, mead (SD) age was 40.9 (12.1) years, and 253 (49.1%) had persistent MDD at 2-year follow-up. Persisters (n = 253) had a higher baseline IDS sum score than remitters (n = 262) (mean [SD] score, 40.2 [8.9] vs 35.1 [7.1]; the test statistic for the difference in IDS sum score was 22 027; P < .001). The test statistic for the difference in network connectivity was 1.79 (P = .01) for the original data, 1.55 for data matched on IDS sum score (P = .04), and 1.65 for partialed out data (P = .02). At the symptom level, fatigue or loss of energy and feeling guilty had the largest difference in importance in persisters' network compared with that of remitters (Cohen d = 1.13 and 1.18, respectively). CONCLUSIONS AND RELEVANCE: This study reports that symptom networks of patients with MDD are related to longitudinal course: persisters exhibited a more densely connected network at baseline than remitters. More pronounced associations between symptoms may be an important determinant of persistence in MDD. PMID- 26561402 TI - Excision Margins of Melanoma Make a Difference: New Data Support an Old Paradigm. PMID- 26561401 TI - Intra-individual lap time variation of the 400-m walk, an early mobility indicator of executive function decline in high-functioning older adults? AB - Higher intra-individual lap time variation (LTV) of the 400-m walk is cross sectionally associated with poorer attention in older adults. Whether higher LTV predicts decline in executive function and whether the relationship is accounted for by slower walking remain unanswered. The main objective of this study was to examine the relationship between baseline LTV and longitudinal change in executive function. We used data from 347 participants aged 60 years and older (50.7% female) from the Baltimore Longitudinal Study of Aging. Longitudinal assessments of executive function were conducted between 2007 and 2013, including attention (Trails A, Digit Span Forward Test), cognitive flexibility and set shifting (Trails B, Delta TMT: Trials B minus Trials A), visuoperceptual speed (Digit Symbol Substitution Test), and working memory (Digit Span Backward Test). LTV and mean lap time (MLT) were obtained from the 400-m walk test concurrent with the baseline executive function assessment. LTV was computed as variability of lap time across ten 40-m laps based on individual trajectories. A linear mixed effects model was used to examine LTV in relation to changes in executive function, adjusted for age, sex, education, and MLT. Higher LTV was associated with greater decline in performance on Trails B (beta = 4.322, p < 0.001) and delta TMT (beta = 4.230, p < 0.001), independent of covariates. Findings remained largely unchanged after further adjustment for MLT. LTV was not associated with changes in other executive function measures (all p > 0.05). In high-functioning older adults, higher LTV in the 400-m walk predicts executive function decline involving cognitive flexibility and set shifting over a long period of time. High LTV may be an early indicator of executive function decline independent of MLT. PMID- 26561403 TI - Global Cancer Surgery, or Lack Thereof: A Wake-Up Call. PMID- 26561404 TI - Surgical Resection Preferences and Perceptions among Medical Oncologists Treating Liver Metastases from Colorectal Cancer. AB - BACKGROUND: Liver resection is a key therapeutic strategy to improve survival in patients with colorectal cancer liver metastases. Underutilization may negatively affect outcomes. Using a Web-based survey and standardized imaging scenarios, this study assessed medical oncologists' (MOs) perceptions of resectability, preferences for chemotherapy sequencing, and referral for surgical consultation in a static patient profile of good performance status and no extrahepatic spread but varying bulk and distribution of disease. METHODS: A total of 190 US-based MOs were surveyed. A single patient profile was created and combined with 10 different sets of liver computed tomographic images displaying a broad spectrum of metastases. Assessments of resectability and ranking were compared with the results obtained from an expert panel of 3 hepatic surgeons. RESULTS: The expert hepatic surgeons designated 8 scans resectable, 1 borderline resectable/convertible, and 1 unresectable. In the 8 resectable cases, 34.4 % of MOS perceived the case to be initially resectable, 41.7 % potentially resectable after chemotherapy response, and 23.9 % unresectable. Increasing number of lesions, larger tumor diameter, and bilateral disease were associated with lower resectability perception (P < 0.01). Among those cases considered resectable by MOs, they preferred initial resection (54.2 %) over neoadjuvant chemotherapy (38.4 %). Initial referral for surgical consultation was generally favored only for cases considered initially resectable by MOs. CONCLUSIONS: This study confirms both potential discrepancies between MOs' and hepatic surgeons' perception of resectability and underutilization of early surgical consultation for patients with potentially resectable colorectal cancer liver metastases and underscores the importance of an evaluation that includes an experienced hepatic surgeon. PMID- 26561405 TI - The Association Between Excision Margins and Local Recurrence in 11,290 Thin (T1) Primary Cutaneous Melanomas: A Case-Control Study. AB - BACKGROUND: At presentation, most primary cutaneous melanomas are "thin" (Breslow thickness <=1 mm, designated T1 in the American Joint Committee on Cancer staging system) and local recurrence (LR) is rare. Most current management guidelines recommend 1 cm surgical excision margins for T1 melanomas, but evidence to support this recommendation is sparse. We sought to identify clinical and pathologic factors associated with LR in patients with T1 melanomas that might guide primary tumor management. METHODS: From a large, prospectively collected, single-institution database, patients with primary cutaneous melanomas <=1 mm thick diagnosed between 1970 and 2011 who developed LR were identified and matched with controls. Clinical and pathologic parameters were analyzed for their association with LR. RESULTS: From 11,290 primary melanomas <=1 mm thick, 176 (1.56 %) cases with LR were identified and 176 controls (without LR) were selected. LR occurred after a median time of 37 months (range 3-306 months) and was associated with narrower excision margins (hazard ratio = 0.95, 95 % confidence interval 0.92-0.98, p = 0.001), desmoplastic, acral, and lentigo maligna melanoma subtypes (p = 0.008), and melanomas composed predominantly of spindle cells (p = 0.005). However, Breslow thickness, Clark level, ulceration, mitotic rate, regression, and lymphovascular invasion were not. CONCLUSIONS: LR was associated with <8 mm histologic excision margins (corresponding to <1 cm margins in vivo) and desmoplastic, acral, and lentigo maligna melanoma subtypes. This study provides evidence that a >=1 cm clinical excision margin for thin (T1) primary melanomas reduces the risk of LR. PMID- 26561406 TI - Critical analysis of the published literature about the effects of narghile use on oral health. PMID- 26561407 TI - Microvascular head and neck reconstruction in the elderly: The University of Brescia experience. AB - BACKGROUND: Microvascular reconstruction in head and neck surgery is increasing in the elderly because of prolonged life expectancy. The purpose of this study was to evaluate the impact of age on outcomes after microvascular reconstruction. METHODS: We retrospectively reviewed 453 microvascular reconstructions and stratified patients according to age (40.8% >65 years old). Medical and surgical complications and flap success rates were evaluated according to the American Society of Anesthesiologists (ASA) score for physical status and age. RESULTS: Overall flap success and perioperative mortality were 96.1% and 0.7%, respectively. Minor medical complications were higher in the elderly (28.1% vs 15.3%; p = .001). High ASA scores affected rates of major surgical (20% vs 9.2%; p = .001) and minor medical complications (27.2% vs 13.3%; p < .001). CONCLUSION: Microvascular reconstruction is reliable in the elderly. Age should not be considered a contraindication by itself; comorbidities play a stronger role in predicting adverse events. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1488 E1492, 2016. PMID- 26561408 TI - A Food Transfer Program without a Formal Education Component Modifies Complementary Feeding Practices in Poor Rural Mexican Communities. AB - BACKGROUND: Inadequate complementary feeding partially explains micronutrient deficiencies in the first 2 y of life. To prevent malnutrition, the Mexican government implemented the Programa de Apoyo Alimentario (PAL), which transferred either food baskets containing micronutrient-fortified milk and animal food products or cash to beneficiary families along with educational sessions. OBJECTIVE: This study evaluated the impact of PAL on 2 indicators of complementary feeding: minimum dietary diversity and consumption of iron-rich or iron-fortified foods in children aged 6-23 mo. METHODS: A secondary analysis of the original PAL evaluation design was conducted through a randomized community trial implemented with 3 intervention groups (food basket with education, food basket without education, and cash transfer with education) and a control. The impact of PAL after 14 mo of exposure was estimated in 2 cross-sectional groups of children aged 6-23 mo at baseline and at follow-up in a panel of 145 communities by using difference-in-difference models. Only children who lived in households and communities that were similar between treatment groups at baseline were included in the analysis. These children were identified by using a propensity score. RESULTS: Of the 3 intervention groups, when compared with the control, only the food basket without education group component increased the consumption of iron-rich or iron-fortified foods by 31.2 percentage points (PP) (P < 0.01) and the prevalence of minimum dietary diversity by 21.6 PP (P < 0.01). CONCLUSION: These findings suggest that in order to improve dietary quality in children, food baskets that include fortified complementary foods may be more effective than cash transfers. The fact that the 2 food basket groups differed in the observed impact does not allow for more convincing conclusions to be made about the education component of the program. This trial was registered at clinicaltrials.gov as NCT01304888. PMID- 26561409 TI - Higher Eating Frequency Does Not Decrease Appetite in Healthy Adults. AB - BACKGROUND: Consumption of small, frequent meals is suggested as an effective approach to control appetite and food intake and might be a strategy for weight loss or healthy weight maintenance. Despite much speculation on the topic, scientific evidence is limited to support such a relation in the absence of changes to diet composition. OBJECTIVE: We examined the effects of high compared with low eating frequency (EF) on self-reported appetite as a secondary outcome in a controlled trial. METHODS: We conducted a randomized, crossover intervention trial in 12 participants (4 men, 8 women) who completed 2 isocaloric 3-wk intervention phases of low EF (3 eating occasions/d) compared with high EF (8 eating occasions/d). On the last morning of each study phase, participants completed a 4-h appetite testing session. During the appetite testing session, participants completing the low EF phase consumed a meal at 0800. Participants completing the high EF intervention consumed the same meal spread evenly over 2 eating occasions at 0800 and 1030. Standardized ratings of hunger, desire to eat, fullness, thirst, and nausea were completed every 30 min with the use of paper and-pencil semianchored 100-mm visual analog scales. A composite appetite score was calculated as the mean of hunger, desire to eat, and the inverse of fullness (calculated as 100-fullness rating). Linear regression analysis compared ratings between low EF and high EF conditions. RESULTS: The mean composite appetite score was higher in the high EF condition for the total testing period (baseline through 1200) (P < 0.05) and for the time period from baseline through 1030 (P < 0.001). CONCLUSION: The results from this study in 12 healthy adults do not support the popularized notion that small, frequent meals help to decrease overall appetite. This trial was registered at clinicaltrials.gov as NCT02548026. PMID- 26561410 TI - Common Polymorphisms That Affect Folate Transport or Metabolism Modify the Effect of the MTHFR 677C > T Polymorphism on Folate Status. AB - BACKGROUND: Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms. OBJECTIVE: We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status. METHODS: The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10 methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults. RESULTS: Folate deficiency (PF <7 nmol/L) was observed in 18.8% of the participants. Geometric mean PF (nmol/L) was lower in MTHFR 677TT (10.0; 95% CI: 9.2, 11.9) compared with 677CC (12.4; 95% CI: 11.6, 13.2; P < 0.001). RCF (nmol/L) was lower in MTHFR 677TT (652; 95% CI: 611, 695) compared with 677CC (889; 95% CI: 851, 929; P < 0.001) and in SLC19A1 80AA (776; 95% CI: 733, 822) compared with 80GG (861; 95% CI: 815, 910; P < 0.01). RCF and tHcy (MUmol/L) did not differ in MTHFR + MTRR 677TT/524TT compared with 677CC/524CC: 780 (95% CI: 647, 941) compared with 853 (95% CI: 795, 915; P = 0.99) and 10.2 (95% CI: 8.4, 12.3) compared with 8.9 (95% CI: 8.5, 9.4; P = 0.99), respectively. The RR of lowest-tertile RCF (<=680 nmol/L) was 2.1 (95% CI: 1.0, 4.5) for MTHFR + MTRR 677TT/66GG compared with 677CC/66AA, 2.2 (95% CI: 1.2, 4.1) for MTHFR + MTHFD1 677TT/1958AA compared with 677CC/1958GG, 2.9 (95% CI: 1.4, 6.0) for MTHFR + MTHFD1 677TT/-105TT compared with 677CC/-105CC, and 3.5 (95% CI: 1.5, 8.1) for MTHFR + SLC19A1 677TT/80AA compared with 677CC/80GG. Confining the analysis to the MTHFR 677TT genotype, the risk of lowest-tertile RCF was reduced for MTHFR + MTRR 677TT/66GG compared with 677TT/66AA (RR: 0.5; 95% CI: 0.3, 0.9). CONCLUSIONS: Folate status was lower in the MTHFR 677TT and SLC19A1 80AA genotypes compared with corresponding reference genotypes. Low folate status risk associated with the MTHFR 677TT genotype varied depending on its combination with other polymorphisms. PMID- 26561411 TI - Luisa Pettigrew: curious, persistent, and lucky. PMID- 26561412 TI - [Utility of mass spectrometry in the microbiological diagnosis of candiduria]. PMID- 26561413 TI - Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss. AB - Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumina TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL. PMID- 26561414 TI - Isolation of Multidrug-Resistant Escherichia coli O157 from Goats in the Somali Region of Ethiopia: A Cross-Sectional, Abattoir-Based Study. AB - Toxigenic Escherichia coli (E. coli) are an important cause of gastroenteritis in developing countries. In Ethiopia, gastroenteritis due to food-borne disease is a leading cause of death. Yet, there is no surveillance for E. coli O157 and little is known about the carriage of this pathogen in Ethiopia's livestock. This study aimed to assess the prevalence and levels of antimicrobial resistance of E. coli O157 in goat meat, feces, and environmental samples collected at a large abattoir in the Somali region of Ethiopia. The samples were enriched in modified tryptone broth containing novobiocin, and plated onto sorbitol MacConkey agar. Isolates were confirmed using indole test and latex agglutination. Antimicrobial susceptibility testing was conducted using the disk diffusion method. A total of 235 samples, including 93 goat carcass swabs, 93 cecal contents, 14 water, 20 hand, and 15 knife swabs were collected. Overall, six (2.5%) samples were contaminated with E. coli O157 of which two (2.1%) were isolated from cecal contents, three (3.2%) from carcass swabs, and one (7.1%) from water. All isolates were resistant to at least two of the 18 antimicrobials tested. Two isolates (33.3%) were resistant to more than five antimicrobials. Abattoir facilities and slaughter techniques were conducive to carcass contamination. This study highlights how poor hygiene and slaughter practice can result in contaminated meat, which is especially risky in Ethiopia because of the common practice of eating raw meat. We detect multi-resistance to drugs not used in goats, suggesting that drugs used to treat human infections may be the originators of antimicrobial resistance in livestock in this ecosystem. The isolation of multidrug-resistant E. coli O157 from goats from a remote pastoralist system highlights the need for global action on regulating and monitoring antimicrobial use in both human and animal populations. PMID- 26561415 TI - The dynamic thiol/disulphide homeostasis in inflammatory bowel disease and its relation with disease activity and pathogenesis. PMID- 26561416 TI - Severe acute kidney injury as a complication of collagenous colitis. PMID- 26561417 TI - HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report. PMID- 26561418 TI - Pneumococcal Meningitis and Endocarditis: A Case Report. PMID- 26561419 TI - Glaucoma Severity and Participation in Diverse Social Roles: Does Visual Field Loss Matter? AB - PURPOSE: To assess the association between glaucoma severity and participation in diverse social roles. DESIGN: Cross-sectional survey. PATIENTS AND METHODS: Individuals with glaucoma, 50+, with visual acuity in the better eye >20/50 were enrolled. They were classified into 3 groups based on visual field loss in the better eye: mild [mean deviation (MD)>-6 dB], moderate (MD, -6 to -12 dB), and severe (MD<-12 dB). The validated Social Role Participation Questionnaire assessed respondents' perceptions of the importance, difficulty, and satisfaction with participation in 11 social role domains (eg, community events, travel). Differences between groups were examined using multivariate linear regression analyses. RESULTS: A total of 118 participants (52% female) were included: 60 mild, 29 moderate, and 29 severe. All social role domains were rated as important by all participants except for education and employment. Women (P<0.01), those with a partner (P<0.01), and those who were less depressed (P=0.03) reported higher scores of perceived importance of participating in social activities. Compared with those with mild glaucoma, individuals with severe glaucoma reported significantly more difficulty participating in community/religious/cultural events (P<0.01), travelling (P<0.01), and relationships with family members (P=0.01). They also reported less satisfaction with travelling (P=0.01) and social events (P=0.04). CONCLUSIONS: Participation in diverse social roles is valued by individuals with glaucoma. Severe visual field loss impedes involvement in and satisfaction with activities in community/religious/cultural events, travelling, and relationships with family members. Appropriate community and targeted interventions are needed to allow people with severe glaucoma to maintain active social participation-a key component to successful aging. PMID- 26561420 TI - Early Clinical Results of a Novel Ab Interno Gel Stent for the Surgical Treatment of Open-angle Glaucoma. AB - PURPOSE: To evaluate the intraocular pressure (IOP) lowering effect of the XEN140 microfistula gel stent implant for the surgical treatment of open-angle glaucoma. PATIENTS AND METHODS: Forty-nine eyes of 49 patients with an IOP>18 mm Hg and <=35 mm Hg were studied in a prospective nonrandomized multicenter cohort trial of the surgical implantation of the XEN140 implant in patients with open-angle glaucoma. Complete success was defined as a postoperative IOP<=18 mm Hg with >=20% reduction in IOP at 12 months without any glaucoma medications. Failure was defined as vision loss of light perceptions vision or worse, need for additional glaucoma surgery, or <20% reduction of IOP from baseline. RESULTS: The average age was 64.3 (28.1 to 86.9) years old. Twenty-one eyes had prior failed trabeculectomy with mitomycin C surgery. IOP at 12 months decreased from a mean of 23.1 (+/-4.1) mm Hg to 14.7 (+/-3.7) mm Hg for a 36.4% reduction in IOP from baseline. The number of patients at 12 months who achieved an IOP<=18 mm Hg and >=20% reduction in IOP was 40 (89%). The number of patients who achieved an IOP<=18 mm Hg and >=20% reduction in IOP without antiglaucoma medications was 18 (40%). CONCLUSIONS: The XEN140 gel stent lowers IOP with few complications when implanted for the surgical treatment of open-angle glaucoma. PMID- 26561421 TI - The Influence of Scleral Flap Thickness, Shape, and Sutures on Intraocular Pressure (IOP) and Aqueous Humor Flow Direction in a Trabeculectomy Model. AB - PURPOSE: Intraocular pressure and aqueous humor flow direction determined by the scleral flap immediately after trabeculectomy are critical determinants of the surgical outcome. We used a large-scale model to objectively measure the influence of flap thickness and shape, and suture number and position on pressure difference across the flap and flow of fluid underneath it. METHODS: The model exploits the principle of dynamic and geometric similarity, so while dimensions were up to 30* greater than actual, the flow had similar properties. Scleral flaps were represented by transparent 0.8- and 1.6-mm-thick silicone sheets on an acrylic plate. Dyed 98% glycerin, representing the aqueous humor was pumped between the sheet and plate, and the equilibrium pressure measured with a pressure transducer. Image analysis based on the principle of dye dilution was performed using MATLAB software. RESULTS: The pressure drop across the flap was larger with thinner flaps, due to reduced rigidity and resistance. Doubling the surface area of flaps and reducing the number of sutures from 5 to 3 or 2 also resulted in larger pressure drops. Flow direction was affected mainly by suture number and position, it was less toward the sutures and more toward the nearest free edge of the flap. Posterior flow of aqueous humor was promoted by placing sutures along the sides while leaving the posterior edge free. CONCLUSION: We demonstrate a new physical model which shows how changes in scleral flap thickness and shape, and suture number and position affect pressure and flow in a trabeculectomy. PMID- 26561422 TI - Meta-Analysis of Association of Obstructive Sleep Apnea With Glaucoma. AB - OBJECTIVES: Previous studies suggested that obstructive sleep apnea (OSA) was associated with glaucoma. However, data on this issue are controversial. This study aims to use meta-analysis to determine whether OSA is related to glaucoma. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane library, the Web of Science, and the Chinese BioMedical Literature Database disk databases up to November 20, 2014 for related literature. The association of OSA with glaucoma was assessed by odds ratio (OR) with 95% confidence interval (CI) as the effect size. Then subgroup analysis was performed according to area and glaucoma type. RESULTS: Six primary studies (3 cohort study and 3 case-control studies) were included in this meta-analysis involving 2,288,701 participants. There was a significant association between OSA and glaucoma (adjusted-effect summary for case-control studies OR=2.46; 95% CI, 1.32-4.59, P=0.005) (adjusted-effect summary for cohort studies OR=1.43; 95% CI, 1.21-1.69, P=0.000). There was no significant publication bias. CONCLUSION: OSA was a risk factor for glaucoma. A large number of studies is needed to explore the mechanisms that link OSA with glaucoma. PMID- 26561423 TI - Modified 360-degree Suture Trabeculotomy for Pseudoexfoliation Glaucoma: 12-Month Results. AB - PURPOSE: We aimed to evaluate the 12-month results of a modified 360-degree suture trabeculotomy (ST) technique in patients with pseudoexfoliation glaucoma (XFG). PATIENTS AND METHODS: The modified 360-degree ST was performed on 20 eyes of 20 consecutive patients with XFG resistant to maximal topical treatment. In 8 patients, ST was combined with phacoemulsification. The main outcome measures were the surgical success rate, the mean postoperative intraocular pressure (IOP), the number of antiglaucoma medications, and the operative complications. RESULTS: The baseline IOP (26.55 +/- 8.91) and medications (3.15 +/- 0.81) decreased significantly to 10.90 +/- 2.73 mm Hg and 0.30 +/- 0.80, respectively, at 12 months postoperatively (P<0.001). The magnitude of IOP reduction was 58.9%. Complete and qualified success rates were 68.4% and 94.7%, respectively. The entire circumference of Schlemm's canal was opened successfully in all cases. Hyphema, perforation of the trabeculodesmetic window, posterior synechia, peripheral anterior synechia, and a transient elevation of the IOP were noted. The results are comparable to our 6-month results and other previously published results for circumferential trabeculotomy. CONCLUSIONS: The modified 360-degree ST provides a feasible choice in patients with XFG with a reasonable rate of complications. The 12-month success rates are promising. It can also be combined effectively with the current cataract surgery. PMID- 26561424 TI - Do Intraocular Pressure Measurements Under Anesthesia Reflect the Awake Condition? AB - BACKGROUND: Anesthesia or sedation is needed when intraocular pressure (IOP) measurement is required in certain circumstances. The effect of different anesthetic regimens on the IOP is still debatable. We aimed to evaluate alterations in the IOP under anesthesia with either propofol or different end tidal concentrations of sevoflurane, when compared with the awake state. METHODS: The IOP was measured in both eyes of 20 adult patients undergoing extraocular ophthalmic surgeries at 5 timepoints: before the induction of general anesthesia (under topical anesthesia), after the induction using propofol target-controlled infusion, and under 3 end-tidal concentrations of sevoflurane (0.5%, 2%, and 5%), either in a decreasing (group A) or an increasing (group B) concentration order. RESULTS: With either propofol or sevoflurane anesthesia, the IOP did not differ significantly from the measurement performed during the awake state (no anesthesia), regardless of the concentration of sevoflurane used (in the range of 0.5% to 5%) or the order of sevoflurane administration (from low to high concentration or vice versa). CONCLUSIONS: These data suggest that propofol and sevoflurane are valid anesthetic agents for the evaluation of IOP in adults when anesthesia is needed. PMID- 26561425 TI - Pain, Sleep Disturbance, and Quality of Life Among Palestinian Patients Diagnosed with Cancer. AB - The objective of this descriptive study is to explore the relationships between pain, sleep disturbance, and quality of life among Palestinian patients diagnosed with cancer in the West Bank. A cross-sectional, descriptive-correlational design was used to collect data from 184 patients with cancer. The quality of life questionnaire, visual analogue pain scale, and physical health status were used in data collection. The results showed that the mean score for pain was 5, the best functioning was for cognitive scale (M = 75, SD = 29), the worst symptoms experienced by patients was appetite loss (M = 47, SD = 35), a moderate global health status (M = 53, SD = 27), and the mean for sleep disturbance was 43 (SD = 35). Pain and sleep disturbance showed high negative correlations with functional scales of quality of life and positive with symptom scales. The findings showed that the co-occurrence of pain and sleep disturbance was negatively correlated with quality of life (QoL) and positively with symptom scales. The regression analysis revealed that pain and sleep disturbance accounted for a significant proportion of variance in the QoL (p < 0.001), and the highest proportion was in predicting global health status (41.9 %). The findings of this study give evidence about the importance of assessing pain and sleep quality among Palestinian patients with cancer. PMID- 26561426 TI - HPV Vaccine Awareness and Knowledge Among Women Living with HIV. AB - Cervical cancer risk is increased among women living with HIV (WLH). Human papillomavirus (HPV) vaccination has been shown to be safe and immunogenic among WLH. We examined HPV vaccine awareness and HPV knowledge among WLH. This cross sectional study collected data from 145 WLH between March 2011 and April 2012. An interviewer-administered survey assessed HPV vaccine awareness and knowledge. Stata/IC 13 was used to perform chi-square tests and multivariate logistic regression analyses. Our sample was 90 % non-Hispanic black and 64 % earned <$10,000/year. Few (38 %) had heard of the HPV vaccine. Half (50 %) knew that HPV caused cervical cancer. HPV vaccine awareness was ten times higher among WLH who knew HPV caused cervical cancer (OR = 10.17; 95 % CI 3.82-27.06). HPV vaccine awareness is low among WLH. Cancer prevention efforts aimed at raising awareness about the HPV vaccine and increasing knowledge about HPV are necessary first steps in reducing cervical cancer disparities among WLH. PMID- 26561427 TI - Reveromycin A Administration Prevents Alveolar Bone Loss in Osteoprotegerin Knockout Mice with Periodontal Disease. AB - Chronic periodontal disease is characterized by alveolar bone loss and inflammatory changes. Reveromycin A (RMA) was recently developed and is a unique agent for inhibiting osteoclast activity. This study analysed the effects of RMA in an experimental mouse model of periodontitis involving osteoprotegerin (OPG) knockout mice, specifically, whether it could control osteoclasts and reduce inflammation in periodontal tissue. We examined wild-type (WT) and OPG knockout mice (OPG KO) ligated with wire around contact points on the left first and second molars. RMA was administered twice a day to half of the mice. Using micro computed tomography, we measured the volume of alveolar bone loss between the first and second molars, and also performed histological analysis. The OPG KO RMA+ group had significantly decreased osteoclast counts, alveolar bone loss, attachment loss, and inflammatory cytokine expression 8 weeks after ligation. Thus, RMA may reduce alveolar bone loss and inflamed periodontal tissues in patients with periodontitis. PMID- 26561429 TI - Diversity Arrays Technology-based PCR markers for marker assisted selection of aluminum tolerance in triticale (x Triticosecale Wittmack). AB - The tolerance of triticale (x Triticosecale Wittmack) cultivars to aluminum (Al) stress observed in acid soils is an important agronomic trait affecting seed yield. Traditionally, breeding of Al-tolerant cultivars was selection based; for example, using a physiological test. However, such selection methods are relatively slow and require numerous plants for phenotype evaluation. Alternatively, DNA-based molecular marker systems could be applied to identify markers useful for selection purposes. Among many marker platforms available, Diversity Arrays Technology (DArT) is one of the most promising. DArT markers preselected for conversion to specific PCR assays were chosen based on association mapping studies using diverse materials. Forty-nine DArT markers were selected and tested for redundancy based on their segregation patterns and sequences, and 40 were successfully converted into specific PCR assays. However, only 24 of these proved to be polymorphic. Where possible, the chromosomal locations of the converted markers were verified. The markers assigned to chromosome 7R that were the most highly correlated with Al-tolerant and non tolerant plants were chosen for marker assisted selection using genetically diverse triticale materials. PMID- 26561430 TI - Prehospital Airway Management in Emergency and Trauma Patients: A Cross-sectional Study of Ambulance Service Providers and Staff in a Low- and Middle-income Country. AB - BACKGROUND: Prehospital airway management (AM) is the first priority in the care of emergency and trauma victims as it has shown to improve survival in these patients. OBJECTIVE: The aim of this study was to assess training and knowledge of ambulance staff and availability of AM equipment in ambulances of Karachi, Pakistan. METHODS: This cross-sectional study was conducted from June through September 2014. Interviews were conducted with management of six ambulance service providers and 165 ambulance staff. Data from the management included availability of AM equipment in the ambulances, number and designation of staff sent for emergency calls, and AM training of staff. Ambulance staff were assessed for their awareness, knowledge, and training pertaining to AM. RESULTS: All the ambulance services (A through F) had basic equipment for AM but lacked qualified and trained staff. All services had solo drivers (98.3%) for emergency calls; however, Ambulance Service A also had doctors and paramedics. Only 35.7% (59/165) of ambulance staff had awareness regarding AM, out of which 77.9% (46/59) belonged to Ambulance Service A. Of these 59 staff, 81.4% received some form of AM training. Staff with AM awareness, when assessed for knowledge pertaining to AM steps and AM equipment, had a mean score of 4.7/5 and 8.4/12, respectively. CONCLUSION: Even though ambulances are equipped with basic equipment, due to lack of trained staff, these ambulances only serve the mere purpose of transportation. There is a need to train ambulance staff and increase ambulance to staff ratio to improve prehospital AM and patient survival. PMID- 26561431 TI - Intensive care unit nurse managers' views regarding nurse staffing in their units in South Africa. AB - AIM: To explore the views of the intensive care unit (ICU) nurse managers regarding nurse staffing in the large ICUs. DESIGN AND METHODS: A qualitative design was used to explore the views of the ICU managers. Four individual interviews were conducted with ICU managers. The interviews were audio recorded; transcribed verbatim and content data analysis was undertaken. The settings were ICUs of four private hospitals in the Tshwane metropolitan area in Gauteng Province, South Africa. RESULTS: Two themes that emerged from the data were shortage of competent and trained nurses and problems with agency nurses. Shortage of competent and trained nurses was associated with the global shortage of nurses; and led to increased patient-to-nurse ratios and the use of other categories of nurses, other than professional nurses. The problems with agency nurses were lack of ICU experience and lack of commitment to their professional work. These brought about risks in the provision of quality nursing care. CONCLUSIONS: Adequate numbers of competent and committed nurses is essential for efficient patient care and favourable outcomes in the ICUs. CLINICAL IMPLICATIONS: The findings demonstrate the importance of provision of ICU trained nurses for patient care, rather than nurse staffing simply to balance the numbers. PMID- 26561432 TI - Encoder-Driven Inpainting Strategy in Multiview Video Compression. AB - In free viewpoint video systems, a user has the freedom to select a virtual view from which an image of the 3D scene is rendered, and the scene is commonly represented by color and depth images of multiple nearby viewpoints. In such representation, there exists data redundancy across multiple dimensions: 1) a 3D voxel may be represented by pixels in multiple viewpoint images (inter-view redundancy); 2) a pixel patch may recur in a distant spatial region of the same image due to self-similarity (inter-patch redundancy); and 3) pixels in a local spatial region tend to be similar (inter-pixel redundancy). It is important to exploit these redundancies during inter-view prediction toward effective multiview video compression. In this paper, we propose an encoder-driven inpainting strategy for inter-view predictive coding, where explicit instructions are transmitted minimally, and the decoder is left to independently recover remaining missing data via inpainting, resulting in lower coding overhead. In particular, after pixels in a reference view are projected to a target view via depth-image-based rendering at the decoder, the remaining holes in the target view are filled via an inpainting process in a block-by-block manner. First, blocks are ordered in terms of difficulty-to-inpaint by the decoder. Then, explicit instructions are only sent for the reconstruction of the most difficult blocks. In particular, the missing pixels are explicitly coded via a graph Fourier transform or a sparsification procedure using discrete cosine transform, leading to low coding cost. For blocks that are easy to inpaint, the decoder independently completes missing pixels via template-based inpainting. We apply our proposed scheme to frames in a prediction structure defined by JCT-3V where inter-view prediction is dominant, and experimentally we show that our scheme achieves up to 3-dB gain in peak-signal-to-noise-ratio in reconstructed image quality over a comparable 3D-High Efficiency Video Coding implementation using fixed 16 $?times $ 16 block size. PMID- 26561433 TI - Scalable Coding of Plenoptic Images by Using a Sparse Set and Disparities. AB - One of the light field capturing techniques is the focused plenoptic capturing. By placing a microlens array in front of the photosensor, the focused plenoptic cameras capture both spatial and angular information of a scene in each microlens image and across microlens images. The capturing results in a significant amount of redundant information, and the captured image is usually of a large resolution. A coding scheme that removes the redundancy before coding can be of advantage for efficient compression, transmission, and rendering. In this paper, we propose a lossy coding scheme to efficiently represent plenoptic images. The format contains a sparse image set and its associated disparities. The reconstruction is performed by disparity-based interpolation and inpainting, and the reconstructed image is later employed as a prediction reference for the coding of the full plenoptic image. As an outcome of the representation, the proposed scheme inherits a scalable structure with three layers. The results show that plenoptic images are compressed efficiently with over 60 percent bit rate reduction compared with High Efficiency Video Coding intra coding, and with over 20 percent compared with an High Efficiency Video Coding block copying mode. PMID- 26561434 TI - A Reconfigurable Tangram Model for Scene Representation and Categorization. AB - This paper presents a hierarchical and compositional scene layout (i.e., spatial configuration) representation and a method of learning reconfigurable model for scene categorization. Three types of shape primitives (i.e., triangle, parallelogram, and trapezoid), called tans, are used to tile scene image lattice in a hierarchical and compositional way, and a directed acyclic AND-OR graph (AOG) is proposed to organize the overcomplete dictionary of tan instances placed in image lattice, exploring a very large number of scene layouts. With certain off-the-shelf appearance features used for grounding terminal-nodes (i.e., tan instances) in the AOG, a scene layout is represented by the globally optimal parse tree learned via a dynamic programming algorithm from the AOG, which we call tangram model. Then, a scene category is represented by a mixture of tangram models discovered with an exemplar-based clustering method. On basis of the tangram model, we address scene categorization in two aspects: 1) building a tangram bank representation for linear classifiers, which utilizes a collection of tangram models learned from all categories and 2) building a tangram matching kernel for kernel-based classification, which accounts for all hidden spatial configurations in the AOG. In experiments, our methods are evaluated on three scene data sets for both the configuration-level and semantic-level scene categorization, and outperform the spatial pyramid model consistently. PMID- 26561435 TI - Close Human Interaction Recognition Using Patch-Aware Models. AB - This paper addresses the problem of recognizing human interactions with close physical contact from videos. Due to ambiguities in feature-to-person assignments and frequent occlusions in close interactions, it is difficult to accurately extract the interacting people. This degrades the recognition performance. We, therefore, propose a hierarchical model, which recognizes close interactions and infers supporting regions for each interacting individual simultaneously. Our model associates a set of hidden variables with spatiotemporal patches and discriminatively infers their states, which indicate the person that the patches belong to. This patch-aware representation explicitly models and accounts for discriminative supporting regions for individuals, and thus overcomes the problem of ambiguities in feature assignments. Moreover, we incorporate the prior for the patches to deal with frequent occlusions during interactions. Using the discriminative supporting regions, our model builds cleaner features for individual action recognition and interaction recognition. Extensive experiments are performed on the BIT-Interaction data set and the UT-Interaction data set set #1 and set #2, and validate the effectiveness of our approach. PMID- 26561436 TI - A Decomposition Framework for Image Denoising Algorithms. AB - In this paper, we consider an image decomposition model that provides a novel framework for image denoising. The model computes the components of the image to be processed in a moving frame that encodes its local geometry (directions of gradients and level lines). Then, the strategy we develop is to denoise the components of the image in the moving frame in order to preserve its local geometry, which would have been more affected if processing the image directly. Experiments on a whole image database tested with several denoising methods show that this framework can provide better results than denoising the image directly, both in terms of Peak signal-to-noise ratio and Structural similarity index metrics. PMID- 26561437 TI - Getting ready for host invasion: elevated expression and action of xyloglucan endotransglucosylases/hydrolases in developing haustoria of the holoparasitic angiosperm Cuscuta. AB - Changes in cell walls have been previously observed in the mature infection organ, or haustorium, of the parasitic angiosperm Cuscuta, but are not equally well charted in young haustoria. In this study, we focused on the molecular processes in the early stages of developing haustoria; that is, before the parasite engages in a physiological contact with its host. We describe first the identification of differentially expressed genes in young haustoria whose development was induced by far-red light and tactile stimuli in the absence of a host plant by suppression subtractive hybridization. To improve sequence information and to aid in the identification of the obtained candidates, reference transcriptomes derived from two species of Cuscuta, C. gronovii and C. reflexa, were generated. Subsequent quantitative gene expression analysis with different tissues of C. reflexa revealed that among the genes that were up regulated in young haustoria, two xyloglucan endotransglucosylase/hydrolase (XTH) genes were highly expressed almost exclusively at the onset of haustorium development. The same expression pattern was also found for the closest XTH homologues from C. gronovii. In situ assays for XTH-specific action suggested that xyloglucan endotransglucosylation was most pronounced in the cell walls of the swelling area of the haustorium facing the host plant, but was also detectable in later stages of haustoriogenesis. We propose that xyloglucan remodelling by Cuscuta XTHs prepares the parasite for host infection and possibly aids the invasive growth of the haustorium. PMID- 26561438 TI - Behavioural responses of freshwater planarians after short-term exposure to the insecticide chlorantraniliprole. AB - Recent advances in video tracking technologies provide the tools for a sensitive and reproducible analysis of invertebrate activity under stressful conditions nurturing the field of behavioural ecotoxicology. This study aimed to evaluate behavioural responses of the freshwater planarian Dugesia subtentaculata exposed to a model compound, chlorantraniliprole (CAP). This compound is an anthranilic diamide insecticide and due to its neurotoxic action can, at low concentrations, impair behaviour of exposed organisms. Behavioural endpoints measured included feeding and locomotor activities. Feeding responses were based on planarian predatory behaviour using Chironomus riparius larvae as prey. Locomotion was measured by the traditional planarian locomotor velocity (pLMV) assay and additionally using an automated video tracking system using a Zebrabox((r)) (Viewpoint, France) device. While feeding and pLMV were significantly impaired at 131.7MUg/L CAP, the video tracking system showed that total distance covered by planarians was significantly reduced at concentrations as low as 26.2MUg/L CAP. Our results show that more advanced automated video recording systems can be used in the development of sensitive bioassays allowing a reliable, time- and cost effective quantification of behaviour in aquatic invertebrates. Due to their ecological relevance, behavioural responses should not be disregarded in risk assessment strategies and we advocate the suitability of planarians as suitable organisms for behavioural ecotoxicological studies. PMID- 26561439 TI - Surgical Treatment of Cavernous Malformations Involving the Posterior Limb of the Internal Capsule: Utility and Predictive Value of Preoperative Diffusion Tensor Imaging. AB - OBJECTIVE: The surgical treatment of cavernous malformations involving the posterior limb of the internal capsule (PLIC-CMs) is challenging. The aim of this study was to determine the utility and predictive value of preoperative diffusion tensor imaging (DTI) in the surgical treatment of PLIC-CMs. METHODS: Patients with PLIC-CMs who were surgically treated between September 2012 and June 2015 were reviewed. All patients underwent preoperative DTI. Three major fiber tracts were selected for evaluation: 1) corticospinal tract (CST); 2) arcuate fasciculus (AF); and 3) optic radiation (OR). The utility of preoperative DTI for surgical approach selection and intraoperative navigation was documented. An involvement grading system of the major fibers was applied to determine the predictive value of preoperative DTI. A last modified Rankin Scale (mRS) score of 0-2 was considered a good outcome, and a last mRS >2 was considered a poor outcome. RESULTS: Thirteen patients with 13 PLIC-CMs were reviewed in this study. All the lesions were radically resected via the corridor formed by CST, AF, and OR. None of the patents suffered from mRS >3, and 7 patients (53.8%) got good outcomes at the last clinic visit. The difference between the preoperative mRS scores and last mRS scores was not significant (P = 0.673). The involvement grade of the fiber tracts was significantly associated with the surgical outcome (P = 0.011). CONCLUSIONS: Preoperative DTI may be a promising tool to determine the surgical approach and predict the surgical outcomes in patients with PLIC-CMs. PMID- 26561440 TI - Health and economic benefits of scaling up a home-based neonatal care package in rural India: a modelling analysis. AB - Approximately 900 000 newborn children die every year in India, accounting for 28% of neonatal deaths globally. In 2011, India introduced a home-based newborn care (HBNC) package to be delivered by community health workers across rural areas. We estimate the disease and economic burden that could be averted by scaling up the HBNC in rural India using IndiaSim, an agent-based simulation model, to examine two interventions. In the first intervention, the existing community health worker network begins providing HBNC for rural households without access to home- or facility-based newborn care, as introduced by India's recent programme. In the second intervention, we consider increased coverage of HBNC across India so that total coverage of neonatal care (HBNC or otherwise) in the rural areas of each state reaches at least 90%. We find that compared with a baseline of no coverage, providing the care package through the existing network of community health workers could avert 48 [95% uncertainty range (UR) 34-63] incident cases of severe neonatal morbidity and 5 (95% UR 4-7) related deaths, save $4411 (95% UR $3088-$5735) in out-of-pocket treatment costs, and provide $285 (95% UR $200-$371) in value of insurance per 1000 live births in rural India. Increasing the coverage of HBNC to 90% will avert an additional 9 (95% UR 7-12) incident cases, 1 death (95% UR 0.72-1.33), and $613 (95% UR $430-$797) in out-of-pocket expenditures, and provide $55 (95% UR $39-$72) in incremental value of insurance per 1000 live births. Intervention benefits are greater for lower socioeconomic groups and in the poorer states of Chhattisgarh, Uttarakhand, Bihar, Assam and Uttar Pradesh. PMID- 26561441 TI - Predictors of Third Molar Impaction: A Systematic Review and Meta-analysis. AB - The objective of this meta-analysis was to evaluate the prevalence of third molar (M3) impaction worldwide in individuals >=17 y, from either sex, who had undergone oral radiography and presented with no orofacial syndromes or defects. We performed a literature search using PubMed, ISI Web of Science, and Google Scholar and retrieved English and non-English articles from any period for review. We included studies reporting M3 impaction prevalence based on radiographic examination. Risk of bias was assessed regarding individuals with craniofacial syndromes, prior extraction of permanent teeth, multiple effect size estimates, and studies conflating lack of eruption with impaction. Our search yielded 49 studies involving 83,484 individuals. Worldwide M3 impaction prevalence was found to be 24.40% (95% confidence interval [95% CI]: 18.97% to 30.80%). The odds of M3 impaction in the mandible were 57.58% (95% CI: 43.3% to 68.3%, P < 0.0001) higher than in the maxilla, but we did not detect any difference in the odds of impaction between men and women (18.62%, 95% CI: -4.9% to 48.0%, P = 0.12). Mesioangular impaction was most common (41.17%, 95% CI: 33.8% to 49.0%), followed by vertical (25.55%, 95% CI: 20.0% to 32.0%), distoangular (12.17%, 95% CI: 9.1% to 16.0%), and horizontal (11.06%, 95% CI: 8.3% to 14.6%). Impaction of 1 (42.71%, 95% CI: 30.0% to 56.5%) or 2 (29.64%, 95% CI: 19.5% to 42.3%) M3s was much more common than 3 (12.04%, 95% CI: 7.2% to 19.3%) or 4 (8.74%, 95% CI: 5.2% to 14.5%). There were small differences among impaction prevalence depending on geographic region (F test, P = 0.049). Selection bias was evident because individuals had to undergo radiographic examination to be included in the analysis. The subgroup analysis by sex was underpowered. Worldwide M3 impaction prevalence is lower than previously reported. The percentage of individuals with impacted M3s is much smaller than the percentage that undergoes clinical treatment for M3 problems. PMID- 26561442 TI - Silver Nanoclusters for High-Efficiency Quenching of CdS Nanocrystal Electrochemiluminescence and Sensitive Detection of microRNA. AB - In this work, oligonucleotide-encapusulated silver nanoclusters were applied in the electrochemiluminescence (ECL) system of CdS nanocrystals (NCs)/ K2S2O8 based on dual ECL quenching effects. We found that the ECL emission of CdS NCs matched well with the absorption band of oligonucleotide encapsulated Ag nanoclusters, which could act as the energy acceptor of CdS NCs ECL so as to lead to an effective ECL resonance energy transfer (RET). On the other hand, the Ag nanoclusters could also catalyze electrochemical reduction of K2S2O8, resulting in increased consumption of ECL coreactant near the working electrode and decreased ECL intensity from CdS NCs. On the basis of the dual ECL quenching effects, a sensitive ECL biosensor for detection of microRNA was successfully achieved with a wide linear range from 10 fM to 100 pM. PMID- 26561443 TI - The Mediterranean non-indigenous ascidian Polyandrocarpa zorritensis: Microbiological accumulation capability and environmental implications. AB - We investigated the bacterial accumulation and digestion capability of Polyandrocarpa zorritensis, a non-indigenous colonial ascidian originally described in Peru and later found in the Mediterranean. Microbiological analyses were carried out on homogenates from "unstarved" and "starved" ascidians and seawater from the same sampling site (Adriatic Sea, Italy). Culturable heterotrophic bacteria (22 degrees C), total culturable bacteria (37 degrees C) and vibrios abundances were determined on Marine Agar 2216, Plate Count Agar and TCBS Agar, respectively. Microbial pollution indicators were measured by the most probable number method. All the examined microbiological groups were accumulated by ascidians but differently digested. An interesting outcome is the capability of P. zorritensis to digest allochthonous microorganisms such as coliforms as well as culturable bacteria at 37 degrees C, counteracting the effects of microbial pollution. Thus, the potential exploitation of these filter feeders to restore polluted seawater should be taken into consideration in the management of this alien species. PMID- 26561444 TI - Source determination of benzotriazoles in sediment cores from two urban estuaries on the Atlantic Coast of the United States. AB - Benzotriazoles (BZTs) are used in a broad range of commercial and industrial products, particularly as metal corrosion inhibitors and as ultraviolet (UV) light stabilizer additives in plastics and polymers. In this study, dated sediment cores from two east coast estuaries were analyzed for commonly used BZTs. In Narragansett Bay, UV stabilizing BZTs (UV-BZTs) were present at high levels from 1961 on, reflecting their patent date, local production and long-term preservation in sediment. In Salem Sound, UV-BZTs were present at concentrations consistent with other coastal marine locations not influenced by BZT production. Anticorrosive BZTs (AC-BZTs) were found in both cores, with the highest levels reported to date present in Narragansett Bay, indicating sorption to, and preservation in, sediments. This study revealed that both classes of BZTs have remained structurally intact over time in coastal sediment cores, demonstrating their resistance to degradation and persistence in environmental compartments. PMID- 26561445 TI - Backwash process of marine macroplastics from a beach by nearshore currents around a submerged breakwater. AB - A key factor for determining the residence time of macroplastics on a beach is the process by which the plastics are backwashed offshore (backwash process). Here, we deduced the backwash process of plastic fishing floats on Wadahama Beach based on the analysis of two-year mark-recapture experiments as well as nearshore current structures revealed by sequential images taken by za webcam installed at the edge of a cliff behind the beach. The analysis results revealed the occurrence of a combination of offshore currents and convergence of alongshore currents in the surf zone in storm events around a submerged breakwater off the northern part of the beach, where 48% of the backwashed floats were last found. We conclude that the majority of the floats on the beach were transported alongshore and tended to concentrate in the convergence zone, from where they were backwashed offshore by the nearshore currents generated in the events. PMID- 26561446 TI - Ecotoxicity of bisphenol A to Caenorhabditis elegans by multigenerational exposure and variations of stress response in vivo across generations. AB - In order to understand how bisphenol A (BPA) exposure acts on the evolutionary dynamics of populations and changes of stress response across generations, the model animal Caenorhabditis elegans was used to conduct the multigenerational testing. Multiple endpoints at the physiological (growth, reproduction, and locomotion behaviors) and molecular (stress-related gene expressions) levels were examined by multigenerational exposure to low-concentration BPA (0.001-10 MUM) across four generations. The results showed that changes of physiological-level effects across four generations varied in magnitude and direction, depending on the exposure concentrations. C. elegans individuals in the first generation grew smaller, moved slower, and produced less offsprings than the controls by BPA exposure. As for each trait tested, the first generation response could be commonly mirrored in the subsequent generations at the highest concentration of 10 MUM. However, at lower concentrations, response of parental generation was a relatively poor predictor of the effects on progeny, as acclimation or cumulative damage could occur in the subsequent generations. The integrated gene expression profiles visually illustrated that the tested gene expressions at low concentrations (0.001-0.01 MUM) were more obviously changed in both G1 and G4 generations, and the G1 generation showed a much greater degree of increase in stress-related gene expressions than the G4 generation. The multigenerational toxicity data emphasize the need of considering biological effects over multiple generations to conduct accurate assessment of environmental risks of toxicants on population dynamics. PMID- 26561447 TI - Effect of different carbon nanotubes on cadmium toxicity to Daphnia magna: The role of catalyst impurities and adsorption capacity. AB - Experiments were conducted to investigate the effect of four different carbon nanotubes single- and multi-walled carbon nanotubes (SWCNTs and MWCNTs) and hydroxylated and carboxylated multi-walled carbon nanotubes (OH-MWCNTs and COOH MWCNTs) on Cd toxicity to the aquatic organism Daphnia magna. The acute toxicity results indicated that all CNTs could enhance the toxicity of Cd to D. magna. Furthermore, the filtrate toxicity and adsorption tests showed that the toxicity increasing effect of SWCNTs and MWCNTs in the overall system was mainly caused by catalysts impurities from the pristine CNTs, whereas the greater adsorption of Cd onto OH-MWCNTs (30.52 mg/g) and COOH-MWCNTs (24.93 mg/g) was the key factor contributing to the enhanced toxicity. This result raised a concern that the metal catalyst impurities, adsorption capacities, and accumulation of waterborne CNTs were responsible for the toxicity of Cd to aquatic organism. PMID- 26561448 TI - pH-dependent phosphatization of ZnO nanoparticles and its influence on subsequent lead sorption. AB - Phosphatization of ZnO nanoparticles (ZNPs) at various pHs and its influence on subsequent lead sorption were investigated. Results showed that, in presence of phosphate, both the chemical speciation and crystalline phase of ZNPs were pH dependent that most of them were converted to crystalline Zn3(PO4)2 at acidic pHs, but only little amorphous hopeites can be formed under alkaline condition. Phosphatization process significantly enhanced subsequent lead sorption with the order of acidic process > alkaline > pristine ZNPs. Spectroscopic analysis including ATR-FTIR and XPS revealed main mechanisms of lead phosphate precipitation and inner-sphere complexes for lead sorption on acidic and alkaline treatment products, respectively. The potential toxicity of ZNPs and heavy metals in eutrophic aquatic ecosystems would thus be reduced due to the ubiquitous phosphatization process. This study highlights the importance of environmental variables in exploring the environmental behavior and fate of heavy metals as well as nanoparticles in natural waters. PMID- 26561449 TI - Particle size and chemical constituents of ambient particulate pollution associated with cardiovascular mortality in Guangzhou, China. AB - Though significant associations between particulate matter (PM) air pollution and cardiovascular diseases have been widely reported, it remains unclear what characteristics, such as particle size and chemical constituents, may be responsible for the effects. A time-series model was applied to examine the cardiovascular effects of particle size (for the period of 2009-2011) and chemical constituents (2007-2010) in Guangzhou, we controlled for potential confounders in the model, such as time trends, day of the week, public holidays, meteorological factors and influenza epidemic. We found significant associations of cardiovascular mortality with PM10, PM2.5 and PM1; the excess risk (ER) was 6.10% (95% CI: 1.76%, 10.64%), 6.11% (95% CI: 1.76%, 10.64%) and 6.48% (95% CI: 2.10%, 11.06%) for per IQR increase in PM10, PM2.5 and PM1 at moving averages for the current day and the previous 3 days (lag03), respectively. We did not find significant effects of PM2.5-10 and PM1-2.5. For PM2.5 constituents, we found that organic carbon, elemental carbon, sulfate, nitrate and ammonium were significantly associated with cardiovascular mortality, the corresponding ER for an IQR concentration increase at lag03 was 1.13% (95% CI: 0.10%, 2.17%), 2.77% (95% CI: 0.72%, 4.86%), 2.21% (95% CI: 1.05%, 3.38%), 1.98% (95% CI: 0.54%, 3.44%), and 3.38% (95% CI: 1.56%, 5.23%), respectively. These results were robust to adjustment of other air pollutants and they remained consistent in various sensitivity analyses by changing model parameters. Our study suggests that PM1 and constituents from combustion and secondary aerosols might be important characteristics of PM pollution associated with cardiovascular mortality in Guangzhou. PMID- 26561450 TI - Acoustic stress responses in juvenile sea bass Dicentrarchus labrax induced by offshore pile driving. AB - Underwater sound generated by pile driving during construction of offshore wind farms is a major concern in many countries. This paper reports on the acoustic stress responses in young European sea bass Dicentrarchus labrax (68 and 115 days old), based on four in situ experiments as close as 45 m from a pile driving activity. As a primary stress response, whole-body cortisol seemed to be too sensitive to 'handling' bias. On the other hand, measured secondary stress responses to pile driving showed significant reductions in oxygen consumption rate and low whole-body lactate concentrations. Furthermore, repeated exposure to impulsive sound significantly affected both primary and secondary stress responses. Under laboratory conditions, no tertiary stress responses (no changes in specific growth rate or Fulton's condition factor) were noted in young sea bass 30 days after the treatment. Still, the demonstrated acute stress responses and potentially repeated exposure to impulsive sound in the field will inevitably lead to less fit fish in the wild. PMID- 26561451 TI - Effect of different-sized colloids on the transport and deposition of titanium dioxide nanoparticles in quartz sand. AB - Colloids (non-biological and biological) with different sizes are ubiquitous in natural environment. The investigations regarding the influence of different sized colloids on the transport and deposition behaviors of engineered nanoparticles in porous media yet are still largely lacking. This study investigated the effects of different-sized non-biological and biological colloids on the transport of titanium dioxide nanoparticles (nTiO2) in quartz sand under both electrostatically favorable and unfavorable conditions. Fluorescent carboxylate-modified polystyrene latex microspheres (CML) with sizes of 0.2-2 MUm were utilized as model non-biological colloids, while Gram-negative Escherichia coli (~ 1 MUm) and Gram-positive Bacillus subtilis (~ 2 MUm) were employed as model biological colloids. Under the examined solution conditions, both breakthrough curves and retained profiles of nTiO2 with different-sized CML particles/bacteria were similar as those without colloids under favorable conditions, indicating that the copresence of model colloids in suspensions had negligible effects on the transport and deposition of nTiO2 under favorable conditions. In contrast, higher breakthrough curves and lower retained profiles of nTiO2 with CML particles/bacteria relative to those without copresent colloids were observed under unfavorable conditions. Clearly, the copresence of model colloids increased the transport and decreased the deposition of nTiO2 in quartz sand under unfavorable conditions (solution conditions examined in present study). Both competition of deposition sites on quartz sand surfaces and the enhanced stability/dispersion of nTiO2 induced by copresent colloids were found to be responsible for the increased nTiO2 transport with colloids under unfavorable conditions. Moreover, the smallest colloids had the highest coverage on sand surface and most significant dispersion effect on nTiO2, resulting in the greatest nTiO2 transport. PMID- 26561452 TI - Perfluoroalkyl substances (PFAS) in river and ground/drinking water of the Ganges River basin: Emissions and implications for human exposure. AB - Many perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants. They have been widely used in production processes and daily-use products or may result from degradation of precursor compounds in products or the environment. India, with its developing industrialization and population moving from traditional to contemporary lifestyles, represents an interesting case study to investigate PFAS emission and exposure along steep environmental and socioeconomic gradients. This study assesses PFAS concentrations in river and groundwater (used in this region as drinking water) from several locations along the Ganges River and estimates direct emissions, specifically for PFOS and PFOA. 15 PFAS were frequently detected in the river with the highest concentrations observed for PFHxA (0.4-4.7 ng L(-1)) and PFBS ( 6 MeO-BDE-47 > 6-OH-BDE-47, while 6-OH-BDE-47 was the most prone to acropetal translocation. Debromination rates of BDE-47 were 1.31 and 1.46 times greater than the hydroxylation and methoxylation rates, respectively. Transformation from BDE-47 to lower brominated OH/MeO-PBDEs occurred mainly through debromination first followed by hydroxylation or methoxylation. There was no transformation from 6-OH-BDE-47 or 6-MeO-BDE-47 to PBDEs. Methylation rate of 6-OH-BDE-47 was twice as high as that of 6-MeO-BDE-47 hydroxylation, indicating methylation of 6 OH-BDE-47 was easier and more rapid than hydroxylation of 6-MeO-BDE-47. Debromination and isomerization were potential metabolic pathways for 6-OH-BDE-47 and 6-MeO-BDE-47 in maize. This study provides important information for better understanding the mechanism on plant uptake and transformation of PBDEs. PMID- 26561455 TI - Elemental sulfur coarsening kinetics. AB - BACKGROUND: Elemental sulfur exists is a variety of forms in natural systems, from dissolved forms (noted as S8(diss) or in water as S8(aq)) to bulk elemental sulfur (most stable as alpha-S8). Elemental sulfur can form via several biotic and abiotic processes, many beginning with small sulfur oxide or polysulfidic sulfur molecules that coarsen into S8 rings that then coalesce into larger forms: [Formula: see text] Formation of elemental sulfur can be possible via two primary techniques to create an emulsion of liquid sulfur in water called sulfur sols that approximate some mechanisms of possible elemental sulfur formation in natural systems. These techniques produce hydrophobic (S8(Weimarn)) and hydrophilic (S8(polysulfide)) sols that exist as nanoparticle and colloidal suspensions. These sols begin as small sulfur oxide or polysulfidic sulfur molecules, or dissolved S8(aq) forms, but quickly become nanoparticulate and coarsen into micron sized particles via a combination of classical nucleation, aggregation processes, and/or Ostwald ripening. RESULTS: We conducted a series of experiments to study the rate of elemental sulfur particle coarsening using dynamic light scattering (DLS) analysis under different physical and chemical conditions. Rates of nucleation and initial coarsening occur over seconds to minutes at rates too fast to measure by DLS, with subsequent coarsening of S8(nano) and S8(sol) being strongly temperature dependent, with rates up to 20 times faster at 75 degrees C compared to 20 degrees C. The addition of surfactants (utilizing ionic and nonionic surfactants as model compounds) results in a significant reduction of coarsening rates, in addition to known effects of these molecules on elemental sulfur solubility. DLS and cryo-SEM results suggest coarsening is largely a product of ripening processes rather than particle aggregation, especially at higher temperatures. Fitting of the coarsening rate data to established models for Ostwald ripening additionally support this as a primary mechanism of coarsening. CONCLUSIONS: Elemental sulfur sols coarsen rapidly at elevated temperatures and experience significant effects on both solubility and particle coarsening kinetics due to interaction with surfactants. Growth of elemental sulfur nanoparticles and sols is largely governed by Ostwald ripening processes. PMID- 26561456 TI - Activity of zero-valent sulfur in sulfidic natural waters. AB - BACKGROUND: Ionic and molecular carriers of dissolved (filter-passing) zero valent sulfur (S0) in anaerobic natural waters include polysulfides, Sn2-, molecular S8(aq), organic macromolecules and certain higher valent thioanions. Because S0 is rapidly transferred among these various carriers, its biogeochemical roles in such processes as dehalogenation of organic compounds, chelation of trace metals, and anaerobic microbial metabolism are not determined solely by one ionic or molecular species. Here, S0 is treated collectively as a virtual thermodynamic component, and computational as well as graphical methods for quantifying its activity (aS0) in natural waters are presented. From aS0, concentrations of the ionic and molecular carriers of S0 can be calculated easily. RESULTS: Concentration ratios of any two polysulfide ions define aS0 (Method I). Unfortunately these concentrations are often too low in nature for accurate quantification with current methods. Measurements of total divalent sulfur (SigmaS-II), zero-valent sulfur (SigmaS0) and pH provide a more widely applicable approach (Method II). Systematic errors in SigmaS0 measurements are the main limit to accuracy of this method at the present time. Alternative methods based on greigite solubility and potentiometry are discussed. A critical comparison of Methods I and II reveals inconsistencies at low SigmaS0/SigmaS-II that imply errors in the thermodynamic data for HS2- and S2-. For samples having low SigmaS0/SigmaS-II, an interim remedy is recommended: letting pKa2 = 6.3 for all HSn- ions. CONCLUSIONS: Newly assembled data for aS0 in a selection of anaerobic natural waters indicate that S0 is always metastable in the surveyed samples with respect to disproportionation to sulfide and sulfate. In all the surveyed environments, sulfur-rich minerals, such as greigite, covellite and orpiment, are stable in preference to their sulfur-poor cohorts, mackinawite, chalcocite and realgar. The aS0 values in the dataset span conditions favoring Hg polysulfide complexes vs. Hg-sulfide complexes, implying that aS0 could affect Hg methylation rates in nature. No support is found for the common assumption that aS0 = 1 in reducing natural waters. This paper calls attention to an urgent need for improved measurement methods, especially for total zero-valent sulfur, as well as new determinations of ionization constants for all HSn- species. PMID- 26561457 TI - Occupational medicine is in demise. PMID- 26561458 TI - Visual Analysis of Multi-Run Spatio-Temporal Simulations Using Isocontour Similarity for Projected Views. AB - Multi-run simulations are widely used to investigate how simulated processes evolve depending on varying initial conditions. Frequently, such simulations model the change of spatial phenomena over time. Isocontours have proven to be effective for the visual representation and analysis of 2D and 3D spatial scalar fields. We propose a novel visualization approach for multi-run simulation data based on isocontours. By introducing a distance function for isocontours, we generate a distance matrix used for a multidimensional scaling projection. Multiple simulation runs are represented by polylines in the projected view displaying change over time. We propose a fast calculation of isocontour differences based on a quasi-Monte Carlo approach. For interactive visual analysis, we support filtering and selection mechanisms on the multi-run plot and on linked views to physical space visualizations. Our approach can be effectively used for the visual representation of ensembles, for pattern and outlier detection, for the investigation of the influence of simulation parameters, and for a detailed analysis of the features detected. The proposed method is applicable to data of any spatial dimensionality and any spatial representation (gridded or unstructured). We validate our approach by performing a user study on synthetic data and applying it to different types of multi-run spatio-temporal simulation data. PMID- 26561459 TI - Generalized Local-to-Global Shape Feature Detection Based on Graph Wavelets. AB - Informative and discriminative feature descriptors are vital in qualitative and quantitative shape analysis for a large variety of graphics applications. Conventional feature descriptors primarily concentrate on discontinuity of certain differential attributes at different orders that naturally give rise to their discriminative power in depicting point, line, small patch features, etc. This paper seeks novel strategies to define generalized, user-specified features anywhere on shapes. Our new region-based feature descriptors are constructed primarily with the powerful spectral graph wavelets (SGWs) that are both multi scale and multi-level in nature, incorporating both local (differential) and global (integral) information. To our best knowledge, this is the first attempt to organize SGWs in a hierarchical way and unite them with the bi-harmonic diffusion field towards quantitative region-based shape analysis. Furthermore, we develop a local-to-global shape feature detection framework to facilitate a host of graphics applications, including partial matching without point-wise correspondence, coarse-to-fine recognition, model recognition, etc. Through the extensive experiments and comprehensive comparisons with the state-of-the-art, our framework has exhibited many attractive advantages such as being geometry aware, robust, discriminative, isometry-invariant, etc. PMID- 26561460 TI - Finding the Axis of Revolution of an Algebraic Surface of Revolution. AB - We present an algorithm for extracting the axis of revolution from the implicit equation of an algebraic surface of revolution based on three distinct computational methods: factoring the highest order form into quadrics, contracting the tensor of the highest order form, and using univariate resultants and gcds. We compare and contrast the advantages and disadvantages of each of these three techniques and we derive conditions under which each technique is most appropriate. In addition, we provide several necessary conditions for an implicit algebraic equation to represent a surface of revolution. PMID- 26561461 TI - Efficient Verification of Holograms Using Mobile Augmented Reality. AB - Paper documents such as passports, visas and banknotes are frequently checked by inspection of security elements. In particular, optically variable devices such as holograms are important, but difficult to inspect. Augmented Reality can provide all relevant information on standard mobile devices. However, hologram verification on mobiles still takes long and provides lower accuracy than inspection by human individuals using appropriate reference information. We aim to address these drawbacks by automatic matching combined with a special parametrization of an efficient goal-oriented user interface which supports constrained navigation. We first evaluate a series of similarity measures for matching hologram patches to provide a sound basis for automatic decisions. Then a re-parametrized user interface is proposed based on observations of typical user behavior during document capture. These measures help to reduce capture time to approximately 15 s with better decisions regarding the evaluated samples than what can be achieved by untrained users. PMID- 26561462 TI - Simultaneous Localization and Appearance Estimation with a Consumer RGB-D Camera. AB - Acquiring general material appearance with hand-held consumer RGB-D cameras is difficult for casual users, due to the inaccuracy in reconstructed camera poses and geometry, as well as the unknown lighting that is coupled with materials in measured color images. To tackle these challenges, we present a novel technique for estimating the spatially varying isotropic surface reflectance, solely from color and depth images captured with an RGB-D camera under unknown environment illumination. The core of our approach is a joint optimization, which alternates among solving for plausible camera poses, materials, the environment lighting and normals. To refine camera poses, we exploit the rich spatial and view-dependent variations of materials, treating the object as a localization-self-calibrating model. To recover the unknown lighting, measured color images along with the current estimate of materials are used in a global optimization, efficiently solved by exploiting the sparsity in the wavelet domain. We demonstrate the substantially improved quality of estimated appearance on a variety of daily objects. PMID- 26561463 TI - Surface Mosaic Synthesis with Irregular Tiles. AB - Mosaics are widely used for surface decoration to produce appealing visual effects. We present a method for synthesizing digital surface mosaics with irregularly shaped tiles, which are a type of tiles often used for mosaics design. Our method employs both continuous optimization and combinatorial optimization to improve tile arrangement. In the continuous optimization step, we iteratively partition the base surface into approximate Voronoi regions of the tiles and optimize the positions and orientations of the tiles to achieve a tight fit. Combination optimization performs tile permutation and replacement to further increase surface coverage and diversify tile selection. The alternative applications of these two optimization steps lead to rich combination of tiles and high surface coverage. We demonstrate the effectiveness of our solution with extensive experiments and comparisons. PMID- 26561464 TI - Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma. AB - Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients. PMID- 26561465 TI - MicroRNA-150 functions as a tumor suppressor in osteosarcoma by targeting IGF2BP1. AB - Osteosarcoma (OS) is the most common primary malignant bone tumor with high morbidity in young adults and adolescents. Increasing evidence has demonstrated that aberrant microRNA (miRNA) expression is involved in OS occurrence and development. miR-150 has been recently widely studied in many cancers, but not including OS. This study is aimed to investigate the expression and biological role of miR-150 in OS. Here, we found that miR-150 expression was consistently downregulated in OS tissues and cell lines compared with the matched adjacent normal tissues and human normal osteoblast cells (NHOst), and its expression was significantly correlated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functional study showed that restoration of miR-150 expression in OS cells could inhibit cell proliferation, migration, and invasion and induced apoptosis in vitro as well as suppressed tumor growth of OS in vivo. Mechanistically, IGF2 mRNA-binding protein 1(IGF2BP1) was confirmed to act as a direct target of miR-150, and the IGF2BP1 mRNA expression was inversely correlated with the level of miR-150 in OS tissues. In addition, downregulation of endogenous IGF2BP1 exhibited similar effects of overexpression of miR-150. Taken together, these findings suggest that miR-150 functions as a tumor suppressor in OS partially by targeting IGF2BP1. PMID- 26561466 TI - Lymphocyte to monocyte ratio is associated with response to first-line platinum based chemotherapy and prognosis of early-stage non-small cell lung cancer patients. AB - Lymphocyte to monocyte ratio (LMR) has shown prognostic value in different types of cancer. This study assessed the prognostic performance of LMR in early-stage non-small cell lung cancer (NSCLC) patients and investigated the influence of LMR on the treatment response in patients receiving first-line platinum-based chemotherapy. Four hundred eighty-eight NSCLC patients and 500 healthy donors were enrolled in this study. The cutoff value for LMR was chosen by receiver operating characteristic curve analysis. The prognostic significance of markers was assessed by univariate and multivariate Cox regression models. The median overall survival was 43 months, and the median progression-free survival was 38 months. LMR was associated with disease status and the treatment response of first-line platinum-based chemotherapy. Multivariate analysis showed that LMR was an independent prognostic factor for both overall survival (hazard ratio = 1.53, 95 % confidence interval = 1.09-2.14, P = 0.015) and progression-free survival (hazard ratio = 1.20, 95 % confidence interval = 1.02-1.67, P = 0.028). Furthermore, integration of LMR into a prognostic model including TNM stage, tumor status, chemotherapy, and histological type generated a nomogram, which predicted accurately overall survival for NSCLC patients. Decreased LMR may be a potential biomarker of disease status, worse response to first-line platinum based chemotherapy, and worse survival for NSCLC patients. A prospective study is warranted for further validation of our findings. PMID- 26561467 TI - The protective role of the -1306C>T functional polymorphism in matrix metalloproteinase-2 gene is associated with cervical cancer: implication of human papillomavirus infection. AB - Cervical cancer is the major reproductive health problem among women caused by persistent infection of high-risk human papillomavirus (HR-HPV). Metalloproteinase-2 (MMP-2) is an endopeptidase highly expressed in cervical cancer; however, the genetic link between aberrant expression of MMP-2 and cervical carcinogenesis is not known. The genotypic distribution, expression pattern of MMP-2 and HPV infection, was analyzed in a total of 300 fresh surgically resected cervical tissue biopsies. The MMP-2 C1306T (rs243865) promoter polymorphism dominant model (CC v/s CT + CT + TT) revealed that the CC genotype had a 4.33-fold significant increased risk for development of cervical cancer (OR = 4.33; 95 % CI = 2.36-4.02, p = 0.0001) compared to those with variant genotypes (-1306 CT + TT). The C allele was associated with 3-fold significant increased risk (OR = 2.95; 95 % CI = 1.90-4.60, p = 0.0002) compared to T allele. Interestingly, a significant correlation was found between high expression of MMP-2 protein and CC genotype in cancer patients (p = 0.001) compared to normal controls (p = 0.012). Further analysis showed that the risk of cancer was extremely pronounced in HPV positive patients (OR = 9.33; 95 % CI = 2.88-30.20, p = 0.0001) compared to HPV negative ones, implicating the possible interaction between -1306CC genotype and HPV infection in increasing the cancer risk (p = 0.0001). The leads from the present study suggest the protective role of gene variant -1306C>T at the promoter region of the MMP-2 against HPV-mediated cervical cancer. These findings substantiate the functional role of MMP-2 C1306T polymorphism in a significant downregulation of MMP-2 protein in women with variant genotype (CT/TT) compared to the normal wild CC genotype. PMID- 26561468 TI - Tagging staphylococcal enterotoxin B (SEB) with TGFaL3 for breast cancer therapy. AB - Recent research has attempted to direct superantigens towards tumors by means of tumor-targeted superantigen (TTS) strategy. In this study, we explored the antitumor property of TTS by fusing the third loop of transforming growth factor alpha (TGFalphaL3) to staphylococcal enterotoxin type B (SEB) and investigated the possibility of the therapeutic application of TGFalphaL3-SEB as a novel antitumor candidate in mice bearing breast cancer. Treatment was performed through intratumoral and intravenous injection of TGFalphaL3-SEB. Tumor size/volume, long-term survival, and cytokine secretion were assessed. In addition, the toxicity of each treatment on liver and kidneys was examined. Our results indicated that the relative tumor volume significantly increased in the mice receiving intratumoral TGFaL3-SEB (p < 0.05). Surprisingly, 5 out of the 14 mice were cleared from the tumor thoroughly in 10-25 days after intratumoral administration of TGFaL3-SEB. Quantification of cytokines clearly showed that the mice receiving intratumoral SEB significantly secreted higher interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) compared with the other groups (p < 0.05). The antitumor effect was followed by inhibition of cell proliferation (Ki-67) and micro vascularization (CD31). The highest and lowest levels of tumor necrosis were observed in the intratumoral administration of TGFalphaL3-SEB (85 %) and PBS (14 %), respectively. Intratumoral injection of TGFalphaL3-SEB increased the lifespan of the mice so 37.5 % of them could survive for more than 6 months (p < 0.05). Overall, our findings indicated that intratumoral administration of TGFalphaL3-SEB effectively inhibited the growth of breast tumors through induction of necrosis and suppressing proliferation and angiogenesis without systemic toxicity. PMID- 26561469 TI - The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta analysis. AB - Epigenetic complexes control various pathways within the cells. Their abnormalities can be involved in the initiation and the progression of different types of cancer. Nucleosome remodeling and deacetylase (NuRD) is an epigenetic complex that comprises several subunits such as PHF6. Although PHF6 is reported as a tumor suppressor in some of the hematopoietic malignancies, its function is still challenging in other cancers. Our study aimed at investigating the role of PHF6 in different types of cancer. We conducted a meta-analysis of PHF6 in human cancers at genomic, transcriptomic, and proteomic levels. For this purpose, we acquired the data from several databases, and tried to statistically integrate and analyze the data in order to find the potential role of PHF6 in different tumors. The results demonstrated that although PHF6 has been previously known as a tumor suppressor gene, it was remarkably overexpressed in many cancer types such as breast and colorectal cancers. Notably, PHF6 was under-expressed in a few types of cancer, including esophageal tumors. Moreover, the results indicated that although the mutation rate of PHF6 is relatively low, it is mutated in some tumor types. In addition, our data for 40 epigenetic genes showed that missense and nonsense mutations were associated with overexpression and under-expression, respectively. Our results suggest that PHF6 may function as an oncogenic factor in several types of cancer. We also hypothesize that PHF6 may also play its role in a tissue-specific manner. Our findings suggest further investigations regarding the exact role of PHF6 in tumor types. PMID- 26561470 TI - Subclassification of patients with solitary hepatocellular carcinoma based on post-hepatectomy survival: a large retrospective study. AB - Official guidelines group together all cases of solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion, regardless of tumor size. Here, we examined whether this is justified based on overall survival (OS) after hepatic resection (HR). Patients with newly diagnosed solitary HCC treated by initial HR from January 2004 to October 2013 were classified into six groups based on tumor size (in 2-cm increments). Combining adjacent categories with similar OS led to three groups: <=5 cm (n = 426), >5 and <=8 cm (n = 229), and >8 cm (n = 202). Among all patients, median survival time was 62 months, and OS was 95 % at 1 year, 73 % at 3 years, and 54 % at 5 years. Patients in the <=5 cm group showed significantly higher OS (P < 0.001) and lower tumor recurrence (P = 0.004) than those in the >5 and <=8 cm group, who in turn showed significantly higher OS (P = 0.003) and lower tumor recurrence (P = 0.021) than those in the >8 cm group. Our results suggest that patients with solitary HCC should be subclassified based on tumor size for more accurate prognosis. We propose defining solitary HCC tumors >5 and <=8 cm as "large" and tumors >8 cm as "huge". PMID- 26561471 TI - Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor beta1 induction. AB - The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 MUM) and experimental concentrations of metformin (1000 and 5000 MUM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor beta1 (TGF-beta1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-beta1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer. PMID- 26561472 TI - The prognosis and clinical characteristics of advanced (malignant) solid pseudopapillary neoplasm of the pancreas. AB - Until today, there is no consistency about the prognosis and the diagnostic criteria of the "malignant" pancreatic solid pseudopapillary neoplasms (m-SPNs). We here made a retrospective study of 26 such cases and try to give a comprehensive description of their pathological characteristics and clinical course. We found out that among those malignant cases, the most common involved extrapancreatic organ was the duodenum, followed by the spleen and the portal vein. The lymph node and the liver metastasis were also seen in 19 % cases, respectively. Most of the patients were female (22/26). Calcification, foamy cytoplasm, and bizarre nuclei of tumor cells were more common in male patients. Every patient underwent surgical resection and had excellent prognosis. There were two patients who had metastasis to the liver 6 years after excision. The recurrence status correlated with the family history of malignant tumor. No patient died of the disease directly during the mean follow-up time of 73.9 months (21-135 months). Our results supported the idea that the prognosis of the advanced stage SPNs was excellent. The surgical resection seemed effectively enough for these patients. However, all the patients need close follow-ups, especially those who had family history of malignant tumors. PMID- 26561473 TI - Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells. AB - Acquired radioresistance during radiotherapy has significantly affected the treatment efficacy in esophageal cancer. Many of radioresistant cancer cells demonstrated epithelial-mesenchymal transition (EMT).We found in previous study that a radioresistant cell line (KYSE-150R) possessed EMT characteristic with cyclin D1 overexpression. Cyclin D1 has been demonstrated to affect the radiation sensitivity in cancer cells. To elucidate the molecular functions of cyclin D1 on EMT phenotypes and esophageal cancer radiosensitivity, we treated the radioresistant esophageal cancer cells (KYSE-150R) and parental cells (KYSE-150) with cyclin D1 small interfering RNA (siRNA). The cell proliferation rate of KYSE 150R and the radiation survival fraction were significantly decreased in cyclin D1 siRNA treatment group. Knocking down cyclin D1 resulted in G0/G1 arrest in KYSE-150R cells. The average number of irradiation-induced gamma-H2AX foci increased in the cells treated with cyclin D1 siRNA, indicating impaired DNA double-strand break (DSB) repair in KYSE-150R cells. Cyclin D1 also reversed EMT phenotypes with significantly increased expression of E-cadherin in KYSE-150R cells. However, cyclin D1 siRNA have no radiosensitizing effects on KYSE-150 cells, with no obvious change in EMT marker expression .Our work showed that EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting cyclin D1. PMID- 26561475 TI - Perception of Multisensory Gender Coherence in 6- and 9-month-old Infants. AB - One of the most salient social categories conveyed by human faces and voices is gender. We investigated the developmental emergence of the ability to perceive the coherence of auditory and visual attributes of gender in 6- and 9-month-old infants. Infants viewed two side-by-side video clips of a man and a woman singing a nursery rhyme and heard a synchronous male or female soundtrack. Results showed that 6-month-old infants did not match the audible and visible attributes of gender, and 9-month-old infants matched only female faces and voices. These findings indicate that the ability to perceive the multisensory coherence of gender emerges relatively late in infancy and that it reflects the greater experience that most infants have with female faces and voices. PMID- 26561476 TI - Validation of a Footwear-Based Gait Analysis System With Action-Related Feedback. AB - Quantitative gait analysis enables clinicians to evaluate patient mobility and to diagnose neuromuscular disorders. The clinical application of gait analysis is currently limited by the high operating costs of gait laboratories. The use of instrumented footwear that performs out of the lab measurements on subjects' walking patterns is a promising way to overcome this limitation. Besides serving as assessment tools, such devices can also act as retraining tools that help regulate a patient's gait with acoustic or vibrotactile stimuli. PMID- 26561474 TI - Diagnostic and prognostic value of tissue and circulating levels of Ephrin-A2 in prostate cancer. AB - Ephrin-A2, a member of the Eph/ephrin family, is associated with tumorigenesis and tumor progression. This study aimed to assess the diagnostic and prognostic value of both serum and tissue levels of Ephrin-A2 in prostate cancer (PCa) management. One hundred and forty-five frozen prostate tissues, 55 paraffin embedded prostate tissues, 88 serum samples, and seven prostate cell lines (RWPE 1, LNCaP, LNCaP-LN3, PC-3, PC-3M, PC-3M-LN4, and DU145) were examined via quantitative reverse transcription-PCR (qRT-PCR), immunohistochemistry, enzyme linked immunosorbent assay, and western blotting. Induced Ephrin-A2 messenger RNA (mRNA) or protein expression was detected in 8.6 % (5/58) benign prostatic hyperplasia (BPH), 59.8 % (52/87) PCa, and five prostate cancer cell lines. Ephrin-A2 immunostaining was present in 6.7 % (1/15) patients with BPHs and 62.5 % (25/40) clinically localized PCa. Accordingly, serum Ephrin-A2 was significantly higher in PCa patients compared to those in the BPH patients and controls (P < 0.001). The expression of Ephrin-A2 was higher in tumor patients with an elevated Gleason score or T3-T4 staging. Ephrin-A2 expression was correlated with Ki-67 expression in PCa patients, both at the gene scale and protein level. Our data indicate that Ephrin-A2 is a potential diagnostic and prognostic biomarker and a promising molecular therapeutic target to attenuate prostate cancer progression. PMID- 26561477 TI - Markov Random Field-based Fitting of a Subdivision-based Geometric Atlas. AB - An accurate labeling of a multi-part, complex anatomical structure (e.g., brain) is required in order to compare data across images for spatial analysis. It can be achieved by fitting an object-specific geometric atlas that is constructed using a partitioned, high-resolution deformable mesh and tagging each of its polygons with a region label. Subdivision meshes have been used to construct such an atlas because they can provide a compact representation of a partitioned, multi-resolution, object-specific mesh structure using only a few control points. However, automated fitting of a subdivision mesh-based geometric atlas to an anatomical structure in an image is a difficult problem and has not been sufficiently addressed. In this paper, we propose a novel Markov Random Field based method for fitting a planar, multi-part subdivision mesh to anatomical data. The optimal fitting of the atlas is obtained by determining the optimal locations of the control points. We also tackle the problem of landmark matching in tandem with atlas fitting by constructing a single graphical model to impose pose-invariant, landmark-based geometric constraints on atlas deformation. The atlas deformation is also governed by additional constraints imposed by the mesh's geometric properties and the object boundary. We demonstrate the potential of the proposed method on the difficult problem of segmenting a mouse brain and its interior regions in gene expression images which exhibit large intensity and shape variability. We obtain promising results when compared with manual annotations and prior methods. PMID- 26561478 TI - Calcium Ion Fluctuations Alter Channel Gating in a Stochastic Luminal Calcium Release Site Model. AB - Stochasticity and small system size effects in complex biochemical reaction networks can greatly alter transient and steady-state system properties. A common approach to modeling reaction networks, which accounts for system size, is the chemical master equation that governs the dynamics of the joint probability distribution for molecular copy number. However, calculation of the stationary distribution is often prohibitive, due to the large state-space associated with most biochemical reaction networks. Here, we analyze a network representing a luminal calcium release site model and investigate to what extent small system size effects and calcium fluctuations, driven by ion channel gating, influx and diffusion, alter steady-state ion channel properties including open probability. For a physiological ion channel gating model and number of channels, the state space may be between approximately 106-108 elements, and a novel modified block power method is used to solve the associated dominant eigenvector problem required to calculate the stationary distribution. We demonstrate that both small local cytosolic domain volume and a small number of ion channels drive calcium fluctuations that result in deviation from the corresponding model that neglects small system size effects. PMID- 26561479 TI - Similarity Search of Flexible 3D Molecules Combining Local and Global Shape Descriptors. AB - In this paper, a framework for shape-based similarity search of 3D molecular structures is presented. The proposed framework exploits simultaneously the discriminative capabilities of a global, a local, and a hybrid local-global shape feature to produce a geometric descriptor that achieves higher retrieval accuracy than each feature does separately. Global and hybrid features are extracted using pairwise computations of diffusion distances between the points of the molecular surface, while the local feature is based on accumulating pairwise relations among oriented surface points into local histograms. The local features are integrated into a global descriptor vector using the bag-of-features approach. Due to the intrinsic property of its constituting shape features to be invariant to articulations of the 3D objects, the framework is appropriate for similarity search of flexible 3D molecules, while at the same time it is also accurate in retrieving rigid 3D molecules. The proposed framework is evaluated in flexible and rigid shape matching of 3D protein structures as well as in shape-based virtual screening of large ligand databases with quite promising results. PMID- 26561481 TI - Development of Microelectrode Arrays Using Electroless Plating for CMOS-Based Direct Counting of Bacterial and HeLa Cells. AB - The development of two new types of high-density, electroless plated microelectrode arrays for CMOS-based high-sensitivity direct bacteria and HeLa cell counting are presented. For emerging high-sensitivity direct pathogen counting, two technical challenges must be addressed. One is the formation of a bacteria-sized microelectrode, and the other is the development of a high sensitivity and high-speed amperometry circuit. The requirement for microelectrode formation is that the gold microelectrodes are required to be as small as the target cell. By improving a self-aligned electroless plating technique, the dimensions of the microelectrodes on a CMOS sensor chip in this work were successfully reduced to 1.2 MUm * 2.05 MUm. This is 1/20th of the smallest size reported in the literature. Since a bacteria-sized microelectrode has a severe limitation on the current flow, the amperometry circuit has to have a high sensitivity and high speed with low noise. In this work, a current buffer was inserted to mitigate the potential fluctuation. Three test chips were fabricated using a 0.6- MUm CMOS process: two with 1.2 MUm * 2.05 MUm (1024 * 1024 and 4 * 4) sensor arrays and one with 6- MUm square (16 * 16) sensor arrays; and the microelectrodes were formed on them using electroless plating. The uniformity among the 1024 * 1024 electrodes arranged with a pitch of 3.6 MUm * 4.45 MUm was optically verified. For improving sensitivity, the trenches on each microelectrode were developed and verified optically and electrochemically for the first time. Higher sensitivity can be achieved by introducing a trench structure than by using a conventional microelectrode formed by contact photolithography. Cyclic voltammetry (CV) measurements obtained using the 1.2 MUm * 2.05 MUm 4 * 4 and 6- MUm square 16 * 16 sensor array with electroless-plated microelectrodes successfully demonstrated direct counting of the bacteria-sized microbeads and HeLa cells. PMID- 26561480 TI - INFLUENZA SURVEILLANCE IN RUSSIA BASED ON EPIDEMIOLOGICAL AND LABORATORY DATA FOR THE PERIOD FROM 2005 TO 2012. AB - Exchange of information on and sharing of influenza viruses through the GISRS network has great significance for understanding influenza virus evolution, recognition of a new pandemic virus emergence and for preparing annual WHO recommendations on influenza vaccine strain composition. Influenza surveillance in Russia is based on collaboration of two NICs with 59 Regional Bases. Most epidemiological and laboratory data are entered through the internet into the electronic database at the Research Institute of Influenza (RII), where they are analyzed and then reported to the Ministry of Public Health of Russia. Simultaneously, data are introduced into WHO's Flu Net and Euro Flu, both electronic databases. Annual influenza epidemics of moderate intensity were registered during four pre-pandemic seasons. Children aged 0-2 and 3-6 years were the most affected groups of the population. Influenza registered clinically among hospitalized patients with respiratory infections for the whole epidemic period varied between 1.3 and 5.4% and up but to 18.5-23.0% during the peak of the two pandemic waves caused by influenza A(H1N1) pdm 09 virus and to lesser extent (2.9 to 8.5%) during usual seasonal epidemics. Most epidemics were associated with influenza A(H1N1), A(H3N2) and B co-circulation. During the two pandemic waves (in 2009-2010 and 2010-2011) influenza A(H1N1) pdm 09 predominated. It was accompanied by a rapid growth of influenza morbidity with a significant increase of both hospitalization and mortality. The new pandemic virus displaced the previous seasonal A(H1N1) virus completely. As a rule, most of the influenza viruses circulating in Russia were antigenic ally related to the strains recommended by WHO for vaccine composition for the Northern hemisphere with the exception of two seasons when an unexpected replacement of the influenza B Victoria lineage by Yamagata lineage (2007-2008) and the following return of Victoria lineage viruses (2008-2009) was registered. Influenza surveillance in Russia was improved as a result of enhancing capacity to international standards and the introduction of new methods in NICs such as rRT-PCR diagnosis, regular testing of influenza viruses for susceptibility to antivirals, phylogenetic analysis as well as organization of sentinel surveillance in a number of Regional Base Laboratories. Improvements promoted rapid recognition of the appearance a new pandemic virus in the country and enhancement of confirmation tests in investigation of influenza related death cases. PMID- 26561482 TI - A 5-year experience with an elective scholarly concentrations program. AB - PROBLEM: Programs that encourage scholarly activities beyond the core curriculum and traditional biomedical research are now commonplace among US medical schools. Few studies have generated outcome data for these programs. The goal of the present study was to address this gap. INTERVENTION: The Scholarly Concentration (SC) Program, established in 2006 at the Warren Alpert Medical School of Brown University, is a 4-year elective program that not only encourages students to pursue scholarly work that may include traditional biomedical research but also seeks to broaden students' focus to include less traditional areas. We compared characteristics and academic performance of SC students and non-SC students for the graduating classes of 2010-2014. CONTEXT: Approximately one-third of our students opt to complete an SC during their 4-year undergraduate medical education. Because this program is additional to the regular MD curriculum, we sought to investigate whether SC students sustained the academic achievement of non-SC students while at the same time producing scholarly work as part of the program. OUTCOME: Over 5 years, 35% of students elected to enter the program and approximately 81% of these students completed the program. The parameters that were similar for both SC and non-SC students were age at matriculation, admission route, proportion of undergraduate science majors, and number of undergraduate science courses. Most academic indicators, including United States Medical Licensing Examinations scores, were similar for the two groups; however, SC students achieved more honors in the six core clerkships and were more likely to be inducted into the medical school's two honor societies. Residency specialties selected by graduates in the two groups were similar. SC students published an average of 1.3 peer-reviewed manuscripts per student, higher than the 0.8 manuscripts per non-SC student (p=0.013). CONCLUSIONS: An elective, interdisciplinary scholarly program with a focus beyond traditional biomedical research offers students the opportunity to expand the scope of their medical education without an untoward effect on academic performance or residency placement. PMID- 26561483 TI - A Novel Method to Generate Amplitude-Frequency Modulated Vibrotactile Stimulation. AB - The natural interaction of humans with their environment involves the harmonious coordination of the body, for which multi-modal feedback including vision, proprioception, and tactile perception is essential. Most human-machine interfaces, however, rely on the visual feedback only, and this can lead to considerable cognitive burden. Additional haptic feedback can increase the intuitiveness of the man-machine interaction. Therefore, we propose here a new device able to generate complex vibrotactile stimulation by simultaneously modulating the amplitude and frequency of vibration. Physical measurements were first performed in eight healthy subjects to assess the capability of the device to generate vibrations. The results indicated that the vibration frequency and amplitude can be independently modulated and that the device response to the full range step-change in the amplitude/frequency commands is almost instantaneous and symmetric. In addition, psychophysical assessments were conducted in four healthy subjects using a standard psychophysical procedure (SIAM). The outcomes indicated that the proposed device can produce approximately 400 vixels (discriminable stimuli), which allow for the generation of a high diversity of vibrotactile patterns. The proposed method allows producing different kinds of stimulation patterns using motor types that are suited for specific applications, with adjustable trade-off between vibration intensity, size, and power consumption. PMID- 26561484 TI - Using Concept Mapping in Community-Based Participatory Research: A Mixed Methods Approach. AB - Community-based participatory research (CBPR) has been identified as a useful approach to increasing community involvement in research. Developing rigorous methods in conducting CBPR is an important step in gaining more support for this approach. The current article argues that concept mapping, a structured mixed methods approach, is useful in the initial development of a rigorous CBPR program of research aiming to develop culturally tailored and community-based health interventions for vulnerable populations. A research project examining social dynamics and consequences of alcohol and substance use in Newark, New Jersey, is described to illustrate the use of concept mapping methodology in CBPR. A total of 75 individuals participated in the study. PMID- 26561485 TI - Data-Driven Modeling for UGI Gasification Processes via an Enhanced Genetic BP Neural Network With Link Switches. AB - In this brief, an enhanced genetic back-propagation neural network with link switches (EGA-BPNN-LS) is proposed to address a data-driven modeling problem for gasification processes inside United Gas Improvement (UGI) gasifiers. The online measured temperature of crude gas produced during the gasification processes plays a dominant role in the syngas industry; however, it is difficult to model temperature dynamics via first principles due to the practical complexity of the gasification process, especially as reflected by severe changes in the gas temperature resulting from infrequent manipulations of the gasifier in practice. The proposed data-driven modeling approach, EGA-BPNN-LS, incorporates an NN-LS, an EGA, and the Levenberg-Marquardt (LM) algorithm. The approach cannot only learn the relationships between the control input and the system output from historical data using an optimized network structure through a combination of EGA and NN-LS but also makes use of the networks gradient information via the LM algorithm. EGA-BPNN-LS is applied to a set of data collected from the field to model the UGI gasification processes, and the effectiveness of EGA-BPNN-LS is verified. PMID- 26561486 TI - Is a Complex-Valued Stepsize Advantageous in Complex-Valued Gradient Learning Algorithms? AB - Complex gradient methods have been widely used in learning theory, and typically aim to optimize real-valued functions of complex variables. The stepsize of complex gradient learning methods (CGLMs) is a positive number, and little is known about how a complex stepsize would affect the learning process. To this end, we undertake a comprehensive analysis of CGLMs with a complex stepsize, including the search space, convergence properties, and the dynamics near critical points. Furthermore, several adaptive stepsizes are derived by extending the Barzilai-Borwein method to the complex domain, in order to show that the complex stepsize is superior to the corresponding real one in approximating the information in the Hessian. A numerical example is presented to support the analysis. PMID- 26561487 TI - Multiple Bacteriophage Selection Strategies for Improved Affinity of a Peptide Targeting ERBB2. AB - Due to the heterogeneity of ERBB2-expression between tumors and over the course of treatment, a non-invasive molecular imaging agent is needed to accurately detect overall ERBB2 status. Peptides are a highly advantageous platform for molecular imaging, since they have excellent tumor penetration and rapid pharmacokinetics. One limitation of peptides however, is their traditionally low target affinity, and consequently, tumor uptake. The peptide KCCYSL was previously selected from a bacteriophage (phage) display library to bind ERBB2 and did so with moderate affinity of 295 nM. In order to enhance tumor uptake and clinical utility of the peptide, a novel phage microlibrary was created by flanking the parent sequence with random amino acids, followed by reselection using parallel strategies for high affinity and specific ERBB2 binding in an attempt to affinity maturate the peptide. One limitation of traditional phage display selections is difficulty in releasing the highest affinity phages from the target by incubation of acidic buffer. In an attempt to recover high affinity second-generation peptides from the ERBB2 microlibrary, two elution strategies, sonication and target elution, were undertaken. Sonication resulted in an approximately 50-fold enhancement in recovered phage per round of selection in comparison to target elution. Despite the differences in elution efficiency, the affinities of phage-displayed peptides selected from either strategy were relatively similar. Although both selections yielded peptides with significantly improved affinity in comparison to KCCYSL, the improvements were modest, most likely because the parental peptide binding cannot be improved by additional amino acids. PMID- 26561488 TI - Beyond Lesion-Based Diabetic Retinopathy: A Direct Approach for Referral. AB - Diabetic retinopathy (DR) is the leading cause of blindness in adults, but can be managed if detected early. Automated DR screening helps by indicating which patients should be referred to the doctor. However, current techniques of automated screening still depend too much on the detection of individual lesions. In this study, we bypass lesion detection, and directly train a classifier for DR referral. Additional novelties are the use of state-of-the-art mid-level features for the retinal images: BossaNova and Fisher Vector. Those features extend the classical Bags of Visual Words and greatly improve the accuracy of complex classification tasks. The proposed technique for direct referral is promising, achieving an area under the curve of 96.4%, thus, reducing the classification error by almost 40% over the current state of the art, held by lesion-based techniques. PMID- 26561489 TI - Corrosion Properties of Polydopamine Coatings Formed in One-Step Immersion Process on Magnesium. AB - Polydopamine layers were polymerized directly from Tris(hydroxymethyl)aminomethane-buffered solution in a one-step immersion process onto magnesium surface. Scanning electron microscopy showed successful formation of a ~1 MUm thick layer. ASTM D3359-09 "Tape test" revealed excellent adhesion of the layer. X-ray induced photoelectron spectroscopy and Fourier transform infrared spectroscopy verified the presence of polydopamine on the surface. Corrosion measurements were performed in 0.1 M NaCl solution investigating the influence of coating parameters: dopamine concentration, immersion time, solution pH, and immersion angle. Tafel analysis revealed strong improvement of corrosion behavior compared to bare magnesium. Polydopamine layers prepared with optimized coating procedure showed promising corrosion properties in Dulbecco's modified Eagle medium. In summary, polydopamine coatings offer a simple treatment for magnesium to improve the corrosion behavior and could further act as intermediate layer for further surface functionalization. PMID- 26561490 TI - Allergen immunotherapy in pregnancy. AB - BACKGROUND: Allergic diseases such as asthma and allergic rhinitis constitute a significant burden of disease among women of childbearing age and those who are pregnant. Adequately managing these conditions is paramount in reducing negative fetal outcomes as well as maternal complications during pregnancy. However, the potential for harm to both the mother and fetus demands carefully balancing efficacy and safety of treatment. Allergen immunotherapy (AIT) has emerged as a relatively safe and efficacious mode of therapy in both children and adults. AIT has also been considered for use during pregnancy. METHODS: A review of the literature was conducted for data regarding the safety of initiation and continuation of AIT during pregnancy as well as the effect of AIT on the development of atopy in offspring. MEDLINE and the Cochrane Library were searched for clinical trials, randomized control trials, observational studies and journal articles in English using the terms "Pregnancy" and "Immunotherapy" from 1900 to present. This yielded 4 studies (totaling 422 pregnancies receiving AIT) investigating the continuation of AIT in pregnancy, 2 (totaling 31 pregnancies receiving AIT) evaluating AIT initiation during pregnancy and 5 observing the effect of AIT on atopy in offspring. RESULTS: No significant difference was found in the incidence of prematurity, hypertension (HTN)/proteinuria, congenital malformations or perinatal deaths between the women continued on AIT (both subcutaneous (SC) IT and sublingual (SL) IT to inhalant allergens as well as venom IT) during pregnancy and controls. Similarly, there was no significant difference in maternal or fetal complications between pregnant women initiated on AIT and controls. Among the few pregnant women (10/453 pregnancies) who experienced generalized reactions while receiving AIT, none were found to have fetal complications. Neither SCIT nor SLIT during pregnancy altered the risk of developing atopic disease in offspring. CONCLUSIONS: Based on these data, the continuation of AIT during pregnancy appears safe. Furthermore, the few data available suggest that the initiation of AIT during pregnancy might also be safe, however, more data is required for a definitive conclusion. Lastly, available studies do not show a convincing reduction in the development of atopy in offspring from the administration of AIT during pregnancy. PMID- 26561491 TI - Feature Set Evaluation for Offline Handwriting Recognition Systems: Application to the Recurrent Neural Network Model. AB - The performance of handwriting recognition systems is dependent on the features extracted from the word image. A large body of features exists in the literature, but no method has yet been proposed to identify the most promising of these, other than a straightforward comparison based on the recognition rate. In this paper, we propose a framework for feature set evaluation based on a collaborative setting. We use a weighted vote combination of recurrent neural network (RNN) classifiers, each trained with a particular feature set. This combination is modeled in a probabilistic framework as a mixture model and two methods for weight estimation are described. The main contribution of this paper is to quantify the importance of feature sets through the combination weights, which reflect their strength and complementarity. We chose the RNN classifier because of its state-of-the-art performance. Also, we provide the first feature set benchmark for this classifier. We evaluated several feature sets on the IFN/ENIT and RIMES databases of Arabic and Latin script, respectively. The resulting combination model is competitive with state-of-the-art systems. PMID- 26561492 TI - Bringing Baby-Friendly to the Indian Health Service: A Systemwide Approach to Implementation. AB - The Baby-Friendly Hospital Initiative (BFHI) increases exclusive breastfeeding. Breastfeeding protects against obesity and diabetes, conditions to which American Indians and Alaska Natives are particularly prone. As part of the First Lady'sLet's Move! in Indian Countryinitiative, the US Department of Health and Human Services' Indian Health Service (IHS) began implementing the BFHI in 2011. The IHS administers 13 US birthing hospitals. There are 5 tribally administered hospitals in the lower 48 states that receive IHS funding, and the IHS encouraged them to seek Baby-Friendly designation also. In the 13 federally administered hospitals, the IHS implemented a Baby-Friendly infant feeding policy, extensive clinician training, and Baby-Friendly compatible medical records. All hospitals also became compliant with the World Health Organization's International Code of Marketing of Breast-Milk Substitutes. Strategies and solutions were shared systemwide via webinars and conference calls. Quality improvement methods, technical assistance, and site visits assisted with the implementation process. Between 2011 and December 2014, 100% (13 of 13) of IHS federally administered hospitals gained Baby-Friendly designation. The first Baby-Friendly hospitals in Arizona, New Mexico, North Dakota, Oklahoma, and South Dakota were all IHS sites; 6% of all US Baby-Friendly hospitals are currently IHS hospitals. One tribal site has also been Baby-Friendly designated and 3 of the 5 remaining tribally administered hospitals in the lower 48 states are pursuing Baby-Friendly status. Baby-Friendly Hospital Initiative implementation systemwide is possible in a US government agency serving a high-risk, underprivileged population. Other systems looking to implement the BFHI can learn from the IHS model. PMID- 26561494 TI - The Glass is Half Full and Half Empty: A population-representative twin study testing if Optimism and Pessimism are distinct systems. AB - Optimism and pessimism are associated with important outcomes including health and depression. Yet it is unclear if these apparent polar opposites form a single dimension or reflect two distinct systems. The extent to which personality accounts for differences in optimism/pessimism is also controversial. Here, we addressed these questions in a genetically informative sample of 852 pairs of twins. Distinct genetic influences on optimism and pessimism were found. Significant family-level environment effects also emerged, accounting for much of the negative relationship between optimism and pessimism, as well as a link to neuroticism. A general positive genetics factor exerted significant links among both personality and life-orientation traits. Both optimism bias and pessimism also showed genetic variance distinct from all effects of personality, and from each other. PMID- 26561493 TI - Conversion during thoracoscopic lobectomy: related factors and learning curve impact. AB - Video-assisted thoracoscopic surgery (VATS) lobectomy has become a standard procedure for lung cancer treatment. Conversion-related factors and learning curve impacts, were poorly described. The aim of this study was to review the reasons and related factor for conversion in VATS lobectomy and the impact on this of the surgeon's learning curve. From June 2009 to May 2014, 154 patients who underwent a VATS lobectomy were included in our study. Patients' characteristics, pathology background, operative times, overall length of stay, overall morbidity and type of major complications were recorded for all patients and compared between non converted (n = 133) and converted (n = 21) patients. To evaluate surgeon's learning curve, we analyzed rates and causes of conversion in the first period (first 77 patients) and in the last period (78-154 patients). Patients characteristics were similar between converted and non-converted groups. Patients who were converted to open thoracotomy presented more frecuently tumors >3 cms (P = 0.02). The average of operative times and the length of stay were not significantly different between groups. Overall morbidity and major complications were also similar in both groups. There were no impact of surgeon's learning curve in overall rate conversion in both groups. Emergency conversion was always secondary to vascular accidents, all in the first group (p = 0.059). Surgeons should be expecting to perform a conversion to a thoracotomy in patients who present in preoperative studies, tumors greater than 3 cms. Learning curve only affected the emergency conversion, occurred all in the first half of our series. PMID- 26561495 TI - New 3D virtual human model aims to transform surgical training. PMID- 26561496 TI - Safety of darunavir and atazanavir in HIV-infected children in Europe and Thailand. AB - BACKGROUND: Surveillance for mid- and long-term antiretroviral therapy (ART) toxicity in children is important for informing treatment guidelines. We assessed the safety of darunavir (DRV) and atazanavir (ATV), commonly used as second-line protease inhibitors following lopinavir/ritonavir, in Europe and Thailand. METHODS: Cohorts contributed individual patient data on adverse events (AE) in those aged <18 years taking DRV and ATV, respectively, to 02/2014. Rates of Division of AIDS (DAIDS) grade >=3 laboratory AEs were calculated. RESULTS: Of 431 patients on DRV and 372 on ATV, 317 (74%) and 301 (81%), respectively, had weight and dose data available, of whom 56 (18%) and 33 (9%) took the drugs at a non-approved age or dose. Median age at DRV and ATV start was 14.8 years (IQR 12.8-16.1) and 13.5 years (11.4-15.2); 43% and 26% had received >=8 ART drugs previously. Overall rates of grade >=3 AEs for absolute neutrophils, total cholesterol, triglycerides, pancreatic amylase, lipase and alanine aminotransferase (ALT) were <=3/100 person-years (PY) on approved doses of both drugs, but 66/100 PY (95% CI 52, 84) for bilirubin after <12 months on ATV declining to 32/100 PY (95% CI 23, 44) after >24 months. Five serious drug related clinical AEs were reported in four patients on ATV (one discontinued) and three in three patients on DRV (all discontinued), and did not substantially differ in those on approved compared to non-approved doses. Proportions on the drugs at last follow-up were 89% (383/431) for DRV and 81% (301/372) for ATV (including 73/92 with grade >=3 hyperbilirubinaemia). CONCLUSIONS: AEs were few in number and comparable for the two drugs, with the exception of high rates of hyperbilirubinaemia for ATV; few patients discontinued due to toxicity. PMID- 26561497 TI - Gunshot wound without entrance hole: where is the trick? - a case report and review of the literaturer. AB - The presence at CT scan of more retained bullets than expected could be a very difficult interpretation challenge in the early management of gunshot wounds. The modern non operative management of haemodinamically stable patients without peritonitis requires that the trajectory of the bullet is clearly recognized. This clinical case reporting of a gunshot wound without evident entry hole, allows to discuss the diagnostic and therapeutic implications in the management of gunshot wounds cases with atypical entry and/or exit holes. PMID- 26561498 TI - Highly Sensitive LC-MS-MS Method for the Determination of Tacrine in Rat Plasma: Application to Pharmacokinetic Studies in Rats. AB - A rapid and highly sensitive assay method has been developed and validated for the estimation of tacrine in rat plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves a simple liquid-liquid extraction of tacrine and phenacetin (internal standard, IS) from rat plasma using ethyl acetate. Chromatographic separation was achieved with 0.2% formic acid : acetonitrile (30 : 70, v/v) at a flow rate of 0.50 mL/min on an Atlantis dC18 column with a total run time of 3.0 min. The MS-MS ion transitions monitored were 199.10 -> 171.20 for tacrine and 180.10 -> 110.10 for IS. Method validation was performed as per United States Food and Drug Administration (US FDA) guidelines and the results met the acceptance criteria. The lower limit of quantification achieved was 0.008 ng/mL and linearity was observed from 0.008 to 53.4 ng/mL. The intra- and inter day precision was in the range of 2.76-12.5 and 5.15-12.8%, respectively. This novel method has been applied to a pharmacokinetic study in rats. PMID- 26561499 TI - Are surgeons and anesthesiologists lying to each other or gaming the system? A national random sample survey about "truth-telling practices" in the perioperative setting in the United States. AB - BACKGROUND: The perioperative setting demands strong teamwork to ensure safe patient care, but anecdotally surgeons and anesthesiologists are not always fully truthful with each other. The present study sought to determine the frequency of misrepresentation of the truth in the perioperative setting. METHODS: Direct mailed survey in the United States about misrepresenting information to colleagues in a national random sample of 1130 anesthesiologists and 1130 surgeons. RESULTS: Reflecting the sensitive nature of these questions, only 252 (11 %) surveys were returned-128/1130 by anesthesiologists and 124/1130 by surgeons. While modest numbers of both anesthesiologists (34/128, 27 %) and surgeons (8/124, 7 %) acknowledged misreporting information at least once per month, misreporting was considerably more common among responding anesthesiologists. Among anesthesiologists the majority (68 %) were concerned that surgeons misreported information to them once a month or more often, though only 8 % of surgeons shared reciprocal concerns. More than a third of responding anesthesiologists (36 %) reported having seen their teachers misreport information to surgeons during their training. CONCLUSIONS: These findings, though preliminary due to the small sample, raise concerns about a possible culture of misrepresentation, passed on between generations, in some perioperative environments. Misreporting of information should be examined in more detail and addressed at local levels whenever it is found. Further research is required to determine if the reported behaviors represent routine gaming of perioperative care systems or deliberate and intentional deception. Strategies aimed at fostering conditions in which open honest communication can thrive should be investigated. PMID- 26561500 TI - Single-stage debridement and spinal fusion using PEEK cages through a posterior approach for eradication of lumbar pyogenic spondylodiscitis: a safe treatment strategy for a detrimental condition. AB - BACKGROUND: Pyogenic infections of the lumbar spine are a rare but critical pathology, yet with considerably high mortality rates. In cases indicating surgical therapy, the implantation of titanium cages or autologous bone grafts represent today's gold standard. Although non-metallic implants such as poly ether-ether-ketone (PEEK) have proven to be advantageous in diverse degenerative conditions, their saftey and practicability in lumbar spine infection remains questionable. Moreover, the efficacy of a single-step radical debridement of the infected disc space with subsequent fusion from a strictly posterior approach continues to be an issue of debate. We therefore sought to evaluate the feasibility, clinical and radiological outcome of a single-step TLIF procedure using oblique PEEK cages in the surgical management of patients with lumbar pyogenic spondylodiscitis. METHODS: From January 2009 through December 2013, all patients meeting the indication for surgical treatment of lumbar pyogenic spondylodiscitis were included. Patients demonstrating intact cortical bone on preoperative CT received a single-step radical debridement of the infected intervertebral disc space, posterior screw-and-rod instrumentation and implantation of an oblique PEEK cage using the TLIF technique. Oral antibiotics were continued for 12 weeks postoperatively and clinical and radiological results recorded throughout a minimum 1-year clinical follow-up. RESULTS: A total of 104 patients were admitted to receive surgical therapy for lumbar pyogenic spondylodiscitis. Within this patient population, 18 patients met the diagnostic criteria to receive the implantation of an oblique PEEK cage. Pathogens were detected in 13 cases with Staph. aureus being the predominant causative organism. All patients were discharged to recover in their domestic environment. Throughout the first year of clinical and radiological follow-up and beyond, none of the 18 patients demonstrated any signs of residual neurologic deficits or recurrent infection. Furthermore, two-plane conventional X-rays showed no significant implant subsidence or failure at any of the given time-points in up to 5 years postoperatively. CONCLUSIONS: In patients meeting the criteria for surgical treatment of lumbar pyogenic spondylodiscitis, the implantation of PEEK cages using a single-step TLIF approach is a safe and feasible procedure. Based on our experience, the concern of a recurrent infection when implanting non-metallic cages may be refuted in carefully selected patients. PMID- 26561501 TI - Proctitis after stapled hemorrhoidopexy is an underestimated complication of a widely used surgical procedure: a retrospective observational cohort study in 129 patients. AB - BACKGROUND: Hemorrhoidal disease is highly prevalent in the western world. Stapled hemorrhoidopexy also known as the procedure for prolapsed hemorrhoids (pph) has been shown to be superior to conventional hemorrhoidectomy with regard to postoperative pain, length of hospital stay and early return to work. Proctitis following stapled hemorrhoidopexy has not been reported previously. Herein, we report our experience with proctitis in patients following stapled hemorrhoidopexy and question if proctitis could be a complication of stapled hemorrhoidopexy. MATERIALS AND METHODS: A retrospective analysis of the data of patients undergoing stapled hemorrhoidopexy with the PPH03 in the coloproctology unit of the department of surgery of a primary care hospital in Germany within a 5-year period was performed. All cases were managed and followed up by a single attending surgeon with expertise in coloproctology. RESULTS: 129 patients were included for analysis including 21 cases with grade 2, 103 cases of grade 3 and 5 cases of grade 4 hemorrhoids. The median duration of surgery was 20 min. 17 complications including two recurrences were recorded. Post-pph proctitis was recorded in 14 cases (10.9 %). Post-pph proctitis was not associated with gender, extent of hemorrhoidal disease, BMI and ASA (p >0.05). All cases recovered within 4 weeks following management with nonsteroidal anti-inflammatory drugs and suppositories. CONCLUSION: Proctitis could be a complication of stapled hemorrhoidopexy with a good response to conservative treatment with suppositories. PMID- 26561502 TI - Utilization of surgical safety checklists by urological surgeons in Germany: a nationwide prospective survey. AB - OBJECTIVES: We aimed to investigate the contemporary usage rate and habits of the WHO Surgical Safety Checklist (SSC) in German urological departments. METHODS: We designed a 26-item questionnaire that was sent to all urological departments in Germany. The primary aim of this study was to evaluate the usage rate of the SSC. Secondary aims were to compare perioperative characteristics of users vs. non users of the SSC and to assess circumstances of the SSC application. RESULTS: A total of 213 of 234 (91 %) urological departments were users of the SSC, and 21 (9 %) were non-users. SSC users had more often a standard protocol, took less time and had fewer people involved for checking perioperative patient data compared to non-users. Financial budgeting for the SSC existed in 55 (24 %) departments and for patient safety in 73 (32 %) departments. CONCLUSIONS: The usage rate of the SSC in urological departments in Germany is high despite restricted financial budgeting. Users of the SSC profit by saving time and manpower for checking perioperative patient data. PMID- 26561504 TI - Heavy lifting at work and risk of retinal detachment: a population-based register study in Denmark. AB - OBJECTIVES: To investigate the relationship between rhegmatogenous retinal detachment (RRD) and frequent heavy lifting in a Danish working population through national register data. METHODS: A dynamic cohort of all men aged 20-59 years in Denmark was followed through the Danish Occupational Hospitalisation Register from 1995 to 2010 for diagnosed RRD. Occupational categories were classified according to their potential for heavy lifting in 4 main groups: heavy lifters, manual workers unlikely to be heavy lifters, other manual workers and non-manual workers unlikely to be heavy lifters. The age-standardised rate of diagnosed RRD for heavy lifting occupations was compared with that experienced by the other 3 occupational categories. Rate ratios (RRs) and 95% CIs were estimated through a Poisson regression model adjusted for calendar period and age group. RESULTS: The highest age-standardised rate of diagnosed RRD was recorded among non-manual workers performing occupational activities unlikely to be associated with heavy lifting (18.0 cases per 100,000 person-years). The RR for workers in jobs expected to entail a high frequency of heavy lifting compared with manual workers whose occupation was unlikely to be associated with heavy lifting was 0.91 (95% CI 0.73 to 1.14), while in comparison with other manual workers, it was 0.93 (95% CI 0.78 to 1.11). The RR compared with non-manual workers in occupations unlikely to entail heavy lifting was 0.51 (95% CI 0.43 to 0.60). CONCLUSIONS: These findings do not support an association of occupational heavy lifting with diagnosed RRD. The epidemiological evidence for this association is still inconclusive. Future studies should use a more specific measure of exposure to resolve the outstanding uncertainties. PMID- 26561505 TI - Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers. PMID- 26561506 TI - Author response: Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers. PMID- 26561507 TI - Exposure to MRI-related magnetic fields and vertigo in MRI workers. AB - OBJECTIVES: Vertigo has been reported by people working around magnetic resonance imaging (MRI) scanners and was found to increase with increasing strength of scanner magnets. This suggests an association with exposure to static magnetic fields (SMF) and/or motion-induced time-varying magnetic fields (TVMF). This study assessed the association between various metrics of shift-long exposure to SMF and TVMF and self-reported vertigo among MRI workers. METHODS: We analysed 358 shifts from 234 employees at 14 MRI facilities in the Netherlands. Participants used logbooks to report vertigo experienced during the work day at the MRI facility. In addition, personal exposure to SMF and TVMF was measured during the same shifts, using portable magnetic field dosimeters. RESULTS: Vertigo was reported during 22 shifts by 20 participants and was significantly associated with peak and time-weighted average (TWA) metrics of SMF as well as TVMF exposure. Associations were most evident with full-shift TWA TVMF exposure. The probability of vertigo occurrence during a work shift exceeded 5% at peak exposure levels of 409 mT and 477 mT/s and at full-shift TWA levels of 3 mT and 0.6 mT/s. CONCLUSIONS: These results confirm the hypothesis that vertigo is associated with exposure to MRI-related SMF and TVMF. Strong correlations between various metrics of shift-long exposure make it difficult to disentangle the effects of SMF and TVMF exposure, or identify the most relevant exposure metric. On the other hand, this also implies that several metrics of shift-long exposure to SMF and TVMF should perform similarly in epidemiological studies on MRI related vertigo. PMID- 26561503 TI - Animal models to study acute and chronic intestinal inflammation in mammals. AB - Acute and chronic inflammatory diseases of the intestine impart a significant and negative impact on the health and well-being of human and non-human mammalian animals. Understanding the underlying mechanisms of inflammatory disease is mandatory to develop effective treatment and prevention strategies. As inflammatory disease etiologies are multifactorial, the use of appropriate animal models and associated metrics of disease are essential. In this regard, animal models used alone or in combination to study acute and chronic inflammatory disease of the mammalian intestine paired with commonly used inflammation inducing agents are reviewed. This includes both chemical and biological incitants of inflammation, and both non-mammalian (i.e. nematodes, insects, and fish) and mammalian (i.e. rodents, rabbits, pigs, ruminants, dogs, and non-human primates) models of intestinal inflammation including germ-free, gnotobiotic, as well as surgical, and genetically modified animals. Importantly, chemical and biological incitants induce inflammation via a multitude of mechanisms, and intestinal inflammation and injury can vary greatly according to the incitant and animal model used, allowing studies to ascertain both long-term and short-term effects of inflammation. Thus, researchers and clinicians should be aware of the relative strengths and limitations of the various animal models used to study acute and chronic inflammatory diseases of the mammalian intestine, and the scope and relevance of outcomes achievable based on this knowledge. The ability to induce inflammation to mimic common human diseases is an important factor of a successful animal model, however other mechanisms of disease such as the amount of infective agent to induce disease, invasion mechanisms, and the effect various physiologic changes can have on inducing damage are also important features. In many cases, the use of multiple animal models in combination with both chemical and biological incitants is necessary to answer the specific question being addressed regarding intestinal disease. Some incitants can induce acute responses in certain animal models while others can be used to induce chronic responses; this review aims to illustrate the strengths and weaknesses in each animal model and to guide the choice of an appropriate acute or chronic incitant to facilitate intestinal disease. PMID- 26561508 TI - A fast topological analysis algorithm for large-scale similarity evaluations of ligands and binding pockets. AB - MOTIVATION: With the rapid increase of the structural data of biomolecular complexes, novel structural analysis methods have to be devised with high throughput capacity to handle immense data input and to construct massive networks at the minimal computational cost. Moreover, novel methods should be capable of handling a broad range of molecular structural sizes and chemical natures, cognisant of the conformational and electrostatic bases of molecular recognition, and sufficiently accurate to enable contextually relevant biological inferences. RESULTS: A novel molecular topology comparison method was developed and tested. The method was tested for both ligand and binding pocket similarity analyses and a PDB-wide ligand topological similarity map was computed. CONCLUSION: The unprecedentedly wide scope of ligand definition and large-scale topological similarity mapping can provide very robust tools, of performance unmatched by the present alignment-based methods. The method remarkably shows potential for application for scaffold hopping purposes. It also opens new frontiers in the areas of ligand-mediated protein connectivity, ligand-based molecular phylogeny, target fishing, and off-target predictions. Graphical abstract:A novel molecular topology comparison method based on a combined shape distribution and charge binning scheme is presented. PMID- 26561509 TI - Effective cellular internalization of silica-coated CdSe quantum dots for high contrast cancer imaging and labelling applications. AB - The possibility of developing novel contrast imaging agents for cancer cellular labelling and fluorescence imaging applications were explored using silica-coated cadmium selenide (CdSe) quantum dots (QDs). The time dependent cellular internalization efficiency study was carried out using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Confocal Laser Scanning Microscopy (cLSM) after exposing QDs to stem cells and cancer cells. The strong fluorescence from the cytoplasm confirmed that the QDs were efficiently internalized by the cells. The internalization maxima were observed at the fourth hour of incubation in both stem and cancer cells. Further, the in vitro fluorescence imaging as well as localization study of QDs were performed in various cells. Moreover, high contrast in vivo tumor imaging efficiency of silica-coated CdSe QDs was performed in ultrathin sections of tumor mice, and the results confirmed its effective role in cellular imaging and labelling in cancer and other diseases. PMID- 26561510 TI - Modulation of cytotoxic and genotoxic effects of nanoparticles in cancer cells by external magnetic field. AB - Magnetic nanoparticles are well known for anticancer activity by deregulating cellular functions. In the present study, cellular effects of low strength static magnetic field (SMF) were explored. How nanoparticles affect the cellular response in presence and absence of static magnetic field was also studied. Peripheral blood mononuclear cells (PBMC) and human lymphoma monocytic cell line U937 were chosen as representative normal and cancer cells models. The two effects we would like to report in this paper are, DNA damage induced by SMF of the order of 70 mT, and alteration in membrane potential. The other notable aspect was the changes were diametrically opposite in normal and cancer cell types. DNA damage was observed only in cancer cells whereas membrane depolarization was observed in normal cells. Iron oxide nanoparticles (IONP) and gold nanoparticles (AuNP) were also used for cellular response studies in presence and absence of SMF. The effects of the magnetic nanoparticle IONP and also of AuNP were sensitive to presence of SMF. Unlike cancer cells, normal cells showed a transient membrane depolarization sensitive to static magnetic field. This depolarization effect exclusive for normal cells was suggested to have correlations with their higher repair capacity and lesser propensity for DNA damage. The work shows cancer cells and normal cells respond to nanoparticle and static magnetic field in different ways. The static magnetic induced DNA damage observed exclusively in cancer cells may have therapeutic implications. From the conclusions of the present investigation we may infer that static magnetic field enhances the therapeutic potentials of nanoparticles. Such low strength magnetic field seems to be a promising external manoeuvring agent in designing theranostics. PMID- 26561511 TI - Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems. AB - In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with 99mTc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs. PMID- 26561512 TI - Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment. AB - AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM(r). An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM(r) for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM(r) is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection. We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation. PMID- 26561513 TI - MODELING SOCIAL NETWORKS FROM SAMPLED DATA. AB - Network models are widely used to represent relational information among interacting units and the structural implications of these relations. Recently, social network studies have focused a great deal of attention on random graph models of networks whose nodes represent individual social actors and whose edges represent a specified relationship between the actors. Most inference for social network models assumes that the presence or absence of all possible links is observed, that the information is completely reliable, and that there are no measurement (e.g., recording) errors. This is clearly not true in practice, as much network data is collected though sample surveys. In addition even if a census of a population is attempted, individuals and links between individuals are missed (i.e., do not appear in the recorded data). In this paper we develop the conceptual and computational theory for inference based on sampled network information. We first review forms of network sampling designs used in practice. We consider inference from the likelihood framework, and develop a typology of network data that reflects their treatment within this frame. We then develop inference for social network models based on information from adaptive network designs. We motivate and illustrate these ideas by analyzing the effect of link tracing sampling designs on a collaboration network. PMID- 26561514 TI - Intrinsic Hydrophobic Cairnlike Multilayer Films for Antibacterial Effect with Enhanced Durability. AB - One important aspect of nanotechnology includes thin films capable of being applied to a wide variety of surfaces. Indispensable functions of films include controlled surface energy, stability, and biocompatibility in physiological systems. In this study, we explored the ancient Asian coating material "lacquer" to enhance the physiological and mechanical stability of nanofilms. Lacquer is extracted from the lacquer tree and its main component called urushiol, which is a small molecule that can produce an extremely strong coating. Taking full advantage of layer-by-layer assembly techniques, we successfully fabricated urushiol-based thin films composed of small molecule/polymer multilayers by controlling their molecular interaction. Unique cairnlike nanostructures in this film, produced by urushiol particles, have advantages of intrinsic hydrophobicity and durability against mechanical stimuli at physiological environment. We demonstrated the stability tests as well as the antimicrobial effects of this film. PMID- 26561515 TI - High quality draft genomic sequence of Flavobacterium enshiense DK69(T) and comparison among Flavobacterium genomes. AB - Flavobacterium enshiense DK69(T) is a Gram-negative, aerobic, rod-shaped, non motile and non-flagellated bacterium that belongs to the family Flavobacteriaceae in the phylum Bacteroidetes. The high quality draft genome of strain DK69(T) was obtained and has a 3,375,260 bp genome size with a G + C content of 37.7 mol % and 2848 protein coding genes. In addition, we sequenced five more genomes of Flavobacterium type strains and performed a comparative genomic analysis among 12 Flavobacterium genomes. The results show some specific genes within the fish pathogenic Flavobacterium strains which provide information for further analysis the pathogenicity. PMID- 26561516 TI - High quality draft genome sequence of the moderately halophilic bacterium Pontibacillus yanchengensis Y32(T) and comparison among Pontibacillus genomes. AB - Pontibacillus yanchengensis Y32(T) is an aerobic, motile, Gram-positive, endospore-forming, and moderately halophilic bacterium isolated from a salt field. In this study, we describe the features of P. yanchengensis strain Y32(T) together with a comparison with other four Pontibacillus genomes. The 4,281,464 bp high-quality-draft genome of strain Y32(T) is arranged into 153 contigs containing 3,965 protein-coding genes and 77 RNA encoding genes. The genome of strain Y32(T) possesses many genes related to its halophilic character, flagellar assembly and chemotaxis to support its survival in a salt-rich environment. PMID- 26561517 TI - Complete genome sequence of Paracoccus marcusii phage vB_PmaS-R3 isolated from the South China Sea. AB - Paracoccus spp. are isolated from both terrestrial and aquatic habitats, indicating their ubiquitous existence in the environment. Here we present the first phage isolated from this genus, vB_PmaS-R3, and its complete genome sequence. Paracoccus phage vB_PmaS-R3 is a siphophage isolated from the South China Sea. The genome sequence is 42,093 bp, with a G + C content of 56.36 %. Fifty-two open reading frames were predicted from the genome. The genome can mainly be divided into three regions: genes for DNA metabolism, regulatory genes and structure forming genes. Genes encoding DNA metabolism and structural proteins showed high sequence homology to corresponding genes of Burkholderia phage KL1 and Pseudomonas phage PA73. In addition, four gene transfer agent-like genes were found in the vB_PmaS-R3 genome. A putative L-alanoyl-D-glutamate peptidase was predicted as the endolysin. A MazG gene was found in the vB_PmaS-R3 genome, which indicates genomic adaption to the nutrient-limited marine environment. PMID- 26561518 TI - Balloon post-dilation and valve-in-valve implantation for the reduction of paravalvular leakage with use of the self-expanding CoreValve prosthesis. AB - AIMS: The aims of the study were to evaluate balloon post-dilation (BPD) and valve-in-valve (ViV) implantation for the reduction of paravalvular leakage (PVL) in patients undergoing transcatheter aortic valve implantation (TAVI) with use of the self-expanding CoreValve prosthesis and to assess whether the aortic regurgitation (AR) index can be used to quantify the reduction of PVL by these corrective measures. METHODS AND RESULTS: Angiography and the AR index were used to evaluate the severity of PVL before and after corrective measures in patients suffering from more than mild PVL. Corrective measures were performed in 44.7% (101/226 patients): BPD was performed in 85 patients and ViV implantation in 16 patients, respectively. In 86% (87/101 patients), PVL reduction was successful (no or mild PVL). BPD increased the AR index from 19.1+/-11.0 to 25.9+/-5.8 (p<0.001) and ViV implantation from 17.6+/-6.4 to 29.5+/-9.1 (p=0.008). One-year mortality (21.6% vs. 17.6% vs. 25.0%; p=0.69) and procedural stroke rate (2.4% vs. 2.4% vs. 0%; p=0.82) were not different between patients without corrective measures compared to patients who had undergone corrective measures (BPD or ViV). CONCLUSIONS: BPD and ViV implantation are safe and effective to reduce PVL in TAVI patients. The AR index is useful to quantify the success of these corrective measures for PVL reduction objectively. PMID- 26561519 TI - Sexually dimorphic gene expression in the lateral eyes of Euphilomedes carcharodonta (Ostracoda, Pancrustacea). AB - BACKGROUND: The evolution and development of sexual dimorphism illuminates a central question in biology: How do similar genomes produce different phenotypes? In an XX/XO system especially the state of a sexually dimorphic trait is determined by differences in gene expression, as there are no additional genetic loci in either sex. Here, we examine the XX/XO ostracod crustacean species Euphilomedes carcharodonta. This species exhibits radical sexual dimorphism of their lateral eyes, females have only a tiny simple lateral eye while males have elaborate ommatidial eyes. RESULTS: We find that males express three of nine eye development gene homologs at significantly higher levels during juvenile eye development, compared to females. We also find that most eye-development genes examined are pleiotropic, with high expression levels during embryonic development as well as during juvenile eye development. Later, in adults, we find that phototransduction genes are expressed at higher levels in males than in females, as we might expect when comparing ommatidial to simple eyes. CONCLUSIONS: We show here that expression changes of a handful of developmental genes may underlie the radical difference in a dimorphic character. This work gives an important point of comparison for studying eye evolution and development in the Pancrustacea. PMID- 26561520 TI - Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9. AB - BACKGROUND: Gene therapy strategies are promising therapeutic options for monogenic muscular dystrophies, with several currently underways. The adeno associated viral (AAV) vector is among the most effective gene delivery systems. However, transduction efficiency in skeletal muscles varies between AAV serotypes, with the underlying factors poorly understood. We hypothesized that myofiber-specific tropism differs between AAV serotypes. METHODS: We developed a quantitative histology procedure and generated myofiber pattern maps for four myosin heavy chain (MyHC) isotypes. We compared myofiber pattern maps between AAV6 or AAV9 injected tibialis anterior muscle in mice. We correlated MyHC expression with AAV-derived green fluorescence protein (GFP) expression using statistical models. RESULTS: We found that MyHC-2x expressing myofibers display a significantly higher preference for AAV transduction, whereas MyHC-2b expressing myofibers negatively correlated with AAV transduction. In addition, we show that AAV9-mediated transduction is enriched in myofibers expressing MyHC-1 and MyHC 1/2a. Moreover, AAV9-mediated transduction can predominantly be predicted by the expression of MyHC isotypes. In contrast, AAV6 transduction can be predicted by myofiber size but not by myofiber types. CONCLUSIONS: Our findings identify differences between AAV6 and AAV9 for myofiber-type preferences, which could be an underlying factor for mosaic transduction of skeletal muscle. Adjusting AAV serotype for specific muscle conditions can therefore improve transduction efficacy in clinical applications. PMID- 26561521 TI - Interchangeability and comparative effectiveness between generic and brand montelukast immediate release tablets after a single oral administration in healthy volunteers. AB - BACKGROUND: Montelukast is a leukotriene receptor antagonist. The release of leukotrienes causes narrowing and constricting in the respiratory airways. Blocking the action of these leukotrienes, montelukast can be used for the prophylaxis and treatment of chronic asthma. OBJECTIVE: The aim of this study was to evaluate the interchangeability and comparative effectiveness between a generic and a brand montelukast 10 mg immediate release tablets (Broncast((r)) and Singulair((r)), respectively) after a single oral dose among Arab Mediterranean volunteers. METHODS: An open-label, randomized two-period crossover bioequivalence design was conducted in 31 healthy male volunteers with a 1 week washout between each study period and under fasting conditions. The plasma drug concentration was assessed by using a previously validated LC MS/MS method. The ratio between the generic and brand of geometric least squares means was reported for both generic and brand products. Moreover, an in vitro dissolution study was conducted on generic and brand tablets using three different pH media, and similarity and non-similarity factors (f2 and f1) were calculated. RESULTS: The used bioanalytical method was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient was close to 0.999 during the course of the study validation. Statistical comparison of the main pharmacokinetic parameters showed the inexistence of any significant difference between generic and the brand. The point estimates (ratios of geometric means) were 111.939, 111.711, and 112.169 % for AUC0-24, AUC0-infinity, and Cmax, respectively. The 90 % confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00 % as specified by the FDA and EMA for bioequivalence studies. F2 and f1 were higher than 50 and lower than 15, respectively in all selected pH media. CONCLUSION: Broncast((r)) immediate release film coated tablets (10 mg/tablet) are bioequivalent to Singulair((r)) immediate release film coated tablets (10 mg/tablet), with a comparable safety and efficacy profile. This suggests that these two formulations can be clinically considered interchangeable. The dissolution study suggests that it could be used as premarketing quality control parameter in order to maintain the high quality of the produced product. PMID- 26561522 TI - Risk of postoperative acute kidney injury in patients undergoing orthopaedic surgery--development and validation of a risk score and effect of acute kidney injury on survival: observational cohort study. AB - STUDY QUESTION: What is the predicted risk of acute kidney injury after orthopaedic surgery and does it affect short term and long term survival? METHODS: The cohort comprised adults resident in the National Health Service Tayside region of Scotland who underwent orthopaedic surgery from 1 January 2005 to 31 December 2011. The model was developed in 6220 patients (two hospitals) and externally validated in 4395 patients from a third hospital. Several preoperative variables were selected for candidate predictors, based on literature, clinical expertise, and availability in the orthopaedic surgery setting. The main outcomes were the development of any severity of acute kidney injury (stages 1-3) within the first postoperative week, and 90 day, one year, and longer term survival. STUDY ANSWER AND LIMITATIONS: Using logistic regression analysis, independent predictors of acute kidney injury were older age, male sex, diabetes, number of prescribed drugs, lower estimated glomerular filtration rate, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and American Society of Anesthesiologists grade. The model's predictive performance for discrimination was good (C statistic 0.74 in development cohort, 0.70 in validation cohort). Calibration was good in the development cohort and after recalibration in the validation cohort. Only the highest risks were over predicted. Survival was worse in patients with acute kidney injury compared with those without (adjusted hazard ratio 1.53, 95% confidence interval 1.38 to 1.70). This was most noticeable in the short term (adjusted hazard ratio: 90 day 2.36, 1.94 to 2.87) and diminished over time (90 day-one year 1.40, 1.10 to 1.79; >1 year 1.28, 1.10 to 1.48). The model used routinely collected data in the orthopaedic surgery setting therefore some variables that could potentially improve predictive performance were not available. However, the readily available predictors make the model easily applicable. WHAT THIS STUDY ADDS: A preoperative risk prediction model consisting of seven predictors for acute kidney injury was developed, with good predictive performance in patients undergoing orthopaedic surgery. Survival was significantly poorer in patients even with mild (stage 1) postoperative acute kidney injury. FUNDING, COMPETING INTERESTS, DATA SHARING: SB received grants from Tenovus Tayside, Chief Scientist Office, and the Royal College of Physicians and Surgeons of Glasgow; PT receives grants from Novo Nordisk, GlaxoSmithKline, and the New Drugs Committee of the Scottish Medicines Consortium. No additional data are available. PMID- 26561524 TI - Demographic and clinical risk factors associated with hospital mortality after isolated severe traumatic brain injury: a cohort study. AB - BACKGROUND: Traumatic brain injury (TBI) is a major public health problem and a leading cause of death worldwide. A paucity of literature exists on risk factors for mortality in isolated severe TBI, a condition that is distinct from severe TBI in the setting of multisystem trauma. We determined risk factors for in hospital mortality in this patient population. METHODS: We conducted a retrospective cohort study using data from the National Trauma Databank from 2008 2012 to study all patients admitted with a diagnosis of severe TBI, excluding children, patients with non-isolated TBI, transfers, and hospitalization <48 h. We used multivariable Poisson regression to analyze the association between demographic, clinical, and facility-level characteristics and in-hospital mortality. RESULTS: A total of 41,590 patients were included in our analysis. The cumulative incidence of in-hospital mortality was 10.2 %. In multivariable analysis, older age (RR 3.92, 95 % CI 3.54-4.34), male gender (RR 1.17, 95 % CI 1.09-1.25), admission hypotension (RR 1.83, 95 % CI 1.61-2.09), the need for mechanical ventilation (RR 4.18, 95 % CI 3.64-4.80), higher injury severity score (RR 1.86, 95 % CI 1.41-2.45), and poor initial neurologic grade (RR 3.06, 95 % CI 2.74-3.43) were associated with a higher risk for mortality. CONCLUSIONS: Admission hypotension and the need for mechanical ventilation were possible modifiable risk factors associated with increased in-hospital mortality following isolated severe TBI. Although risk factors for mortality are similar in isolated and non-isolated TBI, the underlying etiologies for hypotension and respiratory failure are likely different in both conditions and require further exploration. PMID- 26561525 TI - Vancomycin-induced acute generalized exanthematous pustulosis (AGEP) masquerading septic shock-an unusual presentation of a rare disease. AB - Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous adverse reaction characterized by acute sterile pustular eruptions, mostly induced by medications. Antibiotics are the most commonly implicated drugs; however, there have only been two previous reports of vancomycin-induced AGEP in the literature. In this case, we present the clinical course of a 56-year-old man who was admitted to the intensive care unit with an unusually severe form of AGEP mimicking septic shock, which developed after the recent use of vancomycin. Despite cessation of the offending agent, our patient continued to clinically decline with development of worsening skin eruptions and hemodynamic instability necessitating vasopressor support. The patient promptly responded to systemic steroid therapy with complete resolution of AGEP. In addition to highlighting the implication of vancomycin in AGEP, we herein discuss the clinical presentation, diagnosis, and management of AGEP, particularly in severe cases admitted to the intensive care unit. PMID- 26561526 TI - Does the frequency and intensity of physical activity in adolescence have an impact on bone? The Tromso Study, Fit Futures. AB - BACKGROUND: Optimization of the genetic potential for bone accrual in early life may prevent future fractures. Possible modification factors include lifestyle factors such as nutrition and physical activity. Measured levels of bone mineral density (BMD) and bone mass content (BMC) are indicators of bone strength, and are correlated with fracture risk. This study explored the impact of self reported physical activity frequencies and intensity on BMD and BMC in Norwegian adolescents. METHODS: In 2010-2011 school students in two North-Norwegian municipalities were invited to a health survey, the Fit Future study. 508 girls and 530 boys aged 15-18 years attended. BMD and BMC were measured by dual X-ray absorptiometry. Physical activity and other lifestyle-factors were reported by questionnaires and clinical interviews. Statistical analyses were performed sex stratified, using ANOVA for comparison of means and linear regression models adjusting for factors known to affect bone. RESULTS: Approximately 2/3 of girls and boys reported themselves as physically active outside school hours. Active participants had a significantly higher BMD and BMC at all sites (p < 0.001), except for BMC total body in girls, compared to inactive participants. In multiple linear regression analyses, increased physical activity measured as days a week, categorized into seldom, moderate and highly, was positively associated with BMD (g/cm(2)) at all sites in girls. Girls reporting themselves as highly active had BMD levels 0.093 g/cm(2), 0.090 g/cm(2) and 0.046 g/cm(2) higher (p < 0.001) than their more seldom active peers at femoral neck, total hip and total body respectively. Corresponding values for boys were 0.125 g/cm(2), 0.133 g/cm(2) and 0.66 g/cm(2). BMC measures showed similar trends at femoral neck and total hip. CONCLUSIONS: Increased level of physical activity is associated with higher BMD and BMC levels in adolescents. For both sexes high activity frequency seems to be essential, whilst boys reporting quite hard intensity has an additional impact. The differential effects of physical activity on bone strength in adolescence have clinical implications, especially in preventive strategies. PMID- 26561528 TI - The effect of castration time on growth and carcass production of elk bulls. AB - The effects of castration time on growth and carcass traits of elk bulls were investigated. Twelve bulls at 5 years old were raised and fed on concentrate with ad libitum hay. All animals were allocated randomly to each of four treatment groups (3 heads/group). Groups of each treatment were castrated surgically in March, April or June and managed together with non-castration (entire) treatment. All elk bulls in the trial were slaughtered at same time. Growth parameters, carcass yield and composition were recorded. The total gain and average daily gain was higher when castrated in April (p < 0.05). The entire elk produced heaviest and highest in saddle and brisket portions (p < 0.05). It is apparent that the castrate animals carried more total fat weight and percentages than the entire males (p < 0.05). It was found that loin muscles from non-castrated elk, in comparison with those from castrated one, had higher content of moisture and lower content of fat (p < 0.05). In this study, growth parameters, carcass yields and chemical composition were greatly affected by castration time. PMID- 26561527 TI - Guidelines for treatment of immune-mediated cerebellar ataxias. AB - Immune-mediated cerebellar ataxias include gluten ataxia, paraneoplastic cerebellar degeneration, GAD antibody associated cerebellar ataxia, and Hashimoto's encephalopathy. Despite the identification of an increasing number of immune-mediated cerebellar ataxias, there is no proposed standardized therapy. We evaluated the efficacies of immunotherapies in reported cases using a common scale of daily activity. The analysis highlighted the importance of removal of autoimmune triggering factors (e.g., gluten or cancer) and the need for immunotherapy evaluation (e.g., corticosteroids, intravenous immunoglobulin, immunosuppressants) and adaptation according to each subtype. PMID- 26561529 TI - Smoking Cessation Intervention on Facebook: Which Content Generates the Best Engagement? AB - BACKGROUND: Social media offer a great opportunity to deliver smoking cessation treatment to young adults, but previous online and social media interventions targeting health behavior change have struggled with low participant engagement. We examined engagement generated by content based on the Transtheoretical Model of Behavior Change (TTM) in a motivationally tailored smoking cessation intervention on Facebook. OBJECTIVE: This study aimed to identify which intervention content based on the TTM (Decisional Balance and 10 processes of change) generated the highest engagement among participants in pre-action stages of change (Precontemplation, Contemplation, and Preparation). METHODS: Participants (N=79, 20% female, mean age 20.8) were assessed for readiness to quit smoking and assigned to one of 7 secret Facebook groups tailored to their stage of change. Daily postings to the groups based on TTM Decisional Balance and the 10 processes of change were made by research staff over 3 months. Engagement was operationalized as the number of participant comments to each post. TTM content-based predictors of number of comments were analyzed and stratified by baseline stage of change, using negative binomial regression analyses with and without zero inflation. RESULTS: A total of 512 TTM-based posts generated 630 individual comments. In Precontemplation and Contemplation groups, Decisional Balance posts generated above average engagement (P=.01 and P<.001). In Contemplation groups, posts based on the TTM processes Dramatic Relief and Self Liberation resulted in below average engagement (P=.01 and P=.005). In Preparation groups, posts based on Consciousness Raising generated above average engagement (P=.009). Participant engagement decreased over time and differed between groups within Precontemplation and Contemplation stages, but was independent of day of the week and time of day the content was posted to the groups. No participant baseline characteristics significantly predicted engagement. CONCLUSIONS: Participants not ready to quit in the next 30 days (in Precontemplation or Contemplation) engaged most when prompted to think about the pros and cons of behavior change, while those in the Preparation stage engaged most when posts increased awareness about smoking and smoking cessation. Findings support tailoring intervention content to readiness to quit and suggest intervention components that may be most effective in generating high participant engagement on social media. PMID- 26561530 TI - Anxiety sensitivity and trait anxiety are associated with response to 7.5% carbon dioxide challenge. AB - The 7.5% carbon dioxide (CO2) inhalation model is used to provoke acute anxiety, for example to investigate the effects of anxiety on cognitive processes, or the efficacy of novel anxiolytic agents. However, little is known about the relationship of baseline anxiety sensitivity or trait anxiety (i.e., anxiety proneness), with an individual's response to the 7.5% CO2 challenge. We examined data from a number of 7.5% CO2 challenge studies to determine whether anxiety proneness was related to subjective or physiological response. Our findings indicate anxiety proneness is associated with greater subjective and physiological responses. However, anxiety-prone individuals also have a greater subjective response to the placebo (medical air) condition. This suggests that anxiety-prone individuals not only respond more strongly to the 7.5% CO2 challenge, but also to medical air. Implications for the design and conduct of 7.5% CO2 challenge studies are discussed. PMID- 26561531 TI - Investigation of the changes of biophysical/mechanical characteristics of differentiating preosteoblasts in vitro. AB - BACKGROUND: Topography, stiffness, and composition of biomaterials play a crucial role in cell behaviors. In this study, we have investigated biochemical (gene markers), biophysical (roughness), and biomechanical (stiffness) changes during the osteogenic differentiation of preosteoblasts on gelatin matrices. RESULTS: Our results demonstrate that gelatin matrices offer a favorable microenvironment for preosteoblasts as determined by focal adhesion and filopodia formation. The osteogenic differentiation potential of preosteoblasts on gelatin matrices is confirmed by qualitative (Alizarin red, von kossa staining, immunofluorescence, and gene expression) and quantitative analyses (alkaline phosphatase activity and calcium content). The biomechanical and biophysical properties of differentiating preosteoblasts are analyzed using atomic force microscopy (AFM) and micro indentation. The results show sequential and significant increases in preosteoblasts roughness and stiffness during osteogenic differentiation, both of which are directly proportional to the progress of osteogenesis. Cell proliferation, height, and spreading area seem to have no direct correlation with differentiation; however, they may be indirectly related to osteogenesis. CONCLUSIONS: The increased stiffness and roughness is attributed to the mineralized bone matrix and enhanced osteogenic extracellular matrix protein. This report indicates that biophysical and biomechanical aspects during in vitro cellular/extracellular changes can be used as biomarkers for the analysis of cell differentiation. PMID- 26561523 TI - A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. AB - Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ~120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration. PMID- 26561533 TI - Editorial Commentary: Scaling Up Antiretroviral Therapy in Africa: Are We There Yet? PMID- 26561532 TI - Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort. AB - BACKGROUND: Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir lamivudine plus nevirapine is used in many resource-constrained settings. METHODS: This retrospective cohort study included patients initiating nevirapine based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. RESULTS: A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. CONCLUSIONS: Compared with zidovudine lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection. PMID- 26561534 TI - Cryopreservation of Gemmae from the Liverwort Marchantia polymorpha L. AB - The liverwort Marchantia polymorpha L. is one of the key model plants in evo-devo studies, and an increasing number of transgenic and mutant lines have been established. For reliable long-term preservation of M. polymorpha plants, spores have been used, but crossing is indispensable to obtain them. Gemmae, however, are vegetative clones and readily available in large numbers without crossing, thereby enabling the clonal preservation and rapid propagation of transgenic or mutant lines. Here, we report a simple cryopreservation protocol for in vitro grown M. polymorpha gemmae using aluminum cryoplates. Gemmae were pre-cultured on sucrose-containing medium, embedded in calcium alginate gel on the surface of a cryoplate, moderately dehydrated and stored in liquid nitrogen. After rapid thawing, the stored gemmae showed a 100% survival rate. Our protocol does not require plant growth regulators such as ABA, and takes only 1 h to complete except for 1 d of pre-culture. Furthermore, gemmae treated as described above but then air-dried for 2 h can be stored at -80 degrees C for at least 1 year without a significant decrease in survival rate, which is convenient for most laboratories that have a -80 degrees C freezer but not a liquid nitrogen container for long-term storage. These preservation techniques for M. polymorpha should increase their availability in the research community. PMID- 26561535 TI - Genome-Wide Transcriptome Analysis During Anthesis Reveals New Insights into the Molecular Basis of Heat Stress Responses in Tolerant and Sensitive Rice Varieties. AB - Rice is one of the main food crops in the world. In the near future, yield is expected to be under pressure due to unfavorable climatic conditions, such as increasing temperatures. Therefore, improving rice germplasm in order to guarantee rice production under harsh environmental conditions is of top priority. Although many physiological studies have contributed to understanding heat responses during anthesis, the most heat-sensitive stage, molecular data are still largely lacking. In this study, an RNA-sequencing approach of heat- and control-treated reproductive tissues during anthesis was carried out using N22, one of the most heat-tolerant rice cultivars known to date. This analysis revealed that expression of genes encoding a number of transcription factor families, together with signal transduction and metabolic pathway genes, is repressed. On the other hand, expression of genes encoding heat shock factors and heat shock proteins was highly activated. Many of these genes are predominantly expressed at late stages of anther development. Further physiological experiments using heat-tolerant N22 and two sensitive cultivars suggest that reduced yield in heat-sensitive plants may be associated with poor pollen development or production in anthers prior to anthesis. In parallel, induction levels of a set of heat-responsive genes in these tissues correlated well with heat tolerance. Altogether, these findings suggest that proper expression of protective chaperones in anthers is needed before anthesis to overcome stress damage and to ensure fertilization. Genes putatively controlling this process were identified and are valuable candidates to consider for molecular breeding of highly productive heat-tolerant cultivars. PMID- 26561536 TI - MicroRNAs and SIRT1: A Strategy for Stem Cell Renewal and Clinical Development? AB - Small non-coding ribonucleic acids (RNAs), known as microRNAs (miRNAs), are now becoming recognized as significant agents that can affect the onset and progression of numerous disorders throughout the body. In particular, miRNAs also may determine stem cell renewal and differentiation. Intimately tied to the ability of miRNAs to govern stem cell proliferation are the proliferative pathways of silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the cell survival mechanisms of autophagy that can be coupled to the activity of the mechanistic target of rapamycin (mTOR). Targeting miRNAs that oversee SIRT1 activity offers interesting prospects for the translation of these pathways into efficacious clinical treatment programs for a host of disorders. Yet, as work in this area progresses, a number of challenges unfold that impact whether manipulation of non-coding RNAs and SIRT1 can finely guide stem cell renewal and differentiation to reach successful clinical outcomes. PMID- 26561537 TI - Integrating a web-based, patient-administered assessment into primary care for HIV-infected adults. AB - Providers routinely under diagnose at risk behaviors and outcomes, including depression, suicidal ideation, substance abuse, and poor medication adherence. To address this, we developed a web-based, self-administered patient-reported assessment tool and integrated it into routine primary care for HIV-infected adults. Printed results were delivered to providers and social workers immediately prior to patient appointments. The assessment included brief, validated instruments measuring clinically relevant domains including depression, substance use, medication adherence, and HIV transmission risk behaviors. Utilizing the Institute for Healthcare Improvement's Plan-Do-Study-Act (PDSA) approach to quality improvement, we addressed issues with clinic flow, technology, scheduling, and delivery of assessment results with the support of all levels of clinic staff. We found web-based patient-reported assessments to be a feasible tool that can be integrated into a busy multi-provider HIV primary care clinic. These assessments may improve provider recognition of key patient behaviors and outcomes. Critical factors for successful integration of such assessments into clinical care include: strong top-level /ort from clinic management, provider understanding of patient-reported assessments as a valuable clinical tool, tailoring the assessment to meet provider needs, communication among clinic staff to address flow issues, timeliness of delivery, and sound technological resources. PMID- 26561539 TI - Balancing Score Adjusted Targeted Minimum Loss-based Estimation. AB - Adjusting for a balancing score is sufficient for bias reduction when estimating causal effects including the average treatment effect and effect among the treated. Estimators that adjust for the propensity score in a nonparametric way, such as matching on an estimate of the propensity score, can be consistent when the estimated propensity score is not consistent for the true propensity score but converges to some other balancing score. We call this property the balancing score property, and discuss a class of estimators that have this property. We introduce a targeted minimum loss-based estimator (TMLE) for a treatment-specific mean with the balancing score property that is additionally locally efficient and doubly robust. We investigate the new estimator's performance relative to other estimators, including another TMLE, a propensity score matching estimator, an inverse probability of treatment weighted estimator, and a regression-based estimator in simulation studies. PMID- 26561538 TI - The combination of dendritic cells-cytotoxic T lymphocytes/cytokine-induced killer (DC-CTL/CIK) therapy exerts immune and clinical responses in patients with malignant tumors. AB - BACKGROUND: The clinical trials using immunotherapy have been performed for the treatment of variety of malignant tumors. However, large-scale meta-analysis of combined DC-CTL/CIK therapy on immune and clinical response in patients has not been well studied yet. The purpose of this study is to investigate the role of DC CTL/CIK therapy and evaluate the changes of immune indicators and tumor serological markers both at an individual level and at a system level, which is an important basis for immunotherapy as well as prognosis estimation. METHODS: Three cohorts were designed to estimate therapeutic effects on patients with malignant tumors. Tumor serological markers were detected pre- and post-treatment by immunoradiometric methods using commercially available diagnostic kits. Lymphocyte subsets were identified by flow cytometry. The quality of life was assessed by EORTC QLQ-C30 questionnaire. RESULTS: In this study, we found out that Tregs was significantly reduced after transfusion of DC-CTL/CIK cells companied by decreasing serological tumor markers including AFP, CA199 and CA242 in primary liver cancer and CA724 in gastric cancer. A system-level analysis showed that lower percentages of Tregs were detected in patients with long lasting courses of immunotherapy. Strikingly, a tumor progression indicator, myeloid-derived suppressor cells (MDSC), was dramatically decreased in patients after DC-CTL/CIK treatment. These results suggested that DC-CTL/CIK therapy improves immune functions and the quality of life post-treatment versus pre therapy, indicating that DC-CTL/CIK therapy might block the deterioration of invasive cancers in these patients. CONCLUSIONS: This study demonstrated that DC CTL/CIK therapy could reduce Tregs, MDSCs, and several crucial serological tumor markers in particular tumors, and improve the function of T cells immune systems and the quality of life in patients with malignant tumor. PMID- 26561540 TI - Identifying Sources of Health Care Underutilization Among California's Immigrants. AB - Many studies show that immigrants face significant barriers in accessing health care. These barriers may be particularly pronounced for newer immigrants, who may face additional obstacles in navigating the health care system. Understanding the sources of health care disparities between recent and non-recent immigrants may allow for better design of policies and interventions to address the vulnerabilities unique to different subgroups of immigrants defined by their length of residency. This study employs descriptive analyses and multivariate logistic regression to estimate the likelihood of accessing and utilizing health care services based on immigration-related factors after controlling for predisposing, enabling, and health care need factors. We also employ a regression based decomposition method to determine whether health care differences between recent and non-recent immigrants are statistically significant and to identify the primary drivers of healthcare differences between recent and non-recent immigrants. The findings support the hypothesis that significant disparities in health care access and utilization exist between recent and non-recent immigrants. We found that health care access and utilization differences between recent and non-recent immigrants were driven primarily by enabling resources, including limited English proficiency (LEP), insurance status, public assistance usage, and poverty level. These results indicate that not only are newer immigrants more likely to underutilize health care, but also that their underutilization is driven primarily by their lack of insurance, lack of adequate financial resources, and inability to navigate the health care system due to LEP. The results further indicate that immigrants with prolonged LEP may be less likely to have a usual source of care and more likely to report delays in obtaining medical treatments, than even recent immigrants with LEP. PMID- 26561541 TI - A Comparison of Birth Outcomes Among Black, Hispanic, and Black Hispanic Women. AB - BACKGROUND: While non-Hispanic Black populations tend to be disproportionately affected by adverse reproductive outcomes, Hispanic populations tend to demonstrate healthier birth outcomes, regardless of socioeconomic background. Little is known about birth outcomes for women who are both Black and Hispanic. We examined whether birth outcomes and risk factors for women who are both Black and Hispanic most closely resemble those of women who are only Black or Hispanic and also compared these outcomes to those for Whites. METHODS: Using the 2013 US natality files, we examined 2,970,315 singleton births to Black Hispanic, Hispanic, Black, and White mothers. We used logistic regression to calculate predicted probabilities of low birth weight (LBW), preterm birth (PTB), or small for gestational age (SGA). Race-stratified regression analysis was used to identify the factors that significantly predicted risk for each outcome for each racial/ethnic group. RESULTS: Black mothers had the highest prevalence and predicted probabilities of experiencing all three outcomes. Black Hispanic mothers were less likely than Black mothers and more likely than Hispanic mothers to experience each of the adverse outcomes. We also found support for racial variation in risk and protective factors for mothers in the different groups. Factors like age and education inconsistently predicted risk of experiencing the birth outcomes for all groups. Overall, Black Hispanic mothers had birth outcomes and risk factor profiles like Hispanic mothers, although they had sociodemographic characteristics and health behaviors like Black mothers. CONCLUSIONS: Patterning of birth outcomes among Black Hispanic women suggest an intersection of risk and protective factors associated with their respective racial and ethnic identities. Additional information about sociodemographic context is needed to develop a more complete picture of how factors related to race and ethnic group membership influence Black Hispanic women's birth outcomes. PMID- 26561542 TI - Effect of metabolic control on oxidative stress, subclinical atherosclerosis and peripheral artery disease in diabetic patients. AB - INTRODUCTION: By rising diabetes mellitus prevalence, the prevalence of its most complication; cardiovascular disease (CVD) is also increasing. Moreover, oxidative stress has important role in pathogenesis of diabetes and its complications. We investigated relationship between total antioxidant status (TAS) and surrogate measures of subclinical atherosclerosis (SA) with glycemic status in diabetics. METHODS & MATERIALS: In a cross-sectional study, we recorded height, weight, waist circumference (WC) and blood pressure of 267 subjects. Blood samples were collected to measure fasting blood sugar (FBS), glycated hemoglobin (HbA1c), lipid profiles and TAS. The surrogate measures of SA were Carotid Intima Media Thickness (CIMT), and Ankle Brachial Index (ABI). RESULTS: We found significantly lower TAS leves and ABI values and higher CIMT in diabetic patients especially in poor glycemic group. There was a nonsignificant, weak correlation between TAS, ABI and CIMT with glycemic status (r = -0.10, -0.16, and +0.09, respectively). Multivariate regression analysis showed a significant influence of increasing age and diabetes duration on worsening CIMT in poor glycemic group. CONCLUSIONS: Our study showed poor glycemic control leads to worse CIMT by increasing age and duration of diabetes. However we did not find a significan correlation between glycemic status and TAS levels. We suggest CIMT measurement along with other SA markers in poor glycemic diabetics, especially in older patients with longer duration of diabetes, to identify high risk CVD patients. PMID- 26561543 TI - Pregnancy complications in women with polycystic ovary syndrome: importance of diagnostic criteria or of phenotypic features? PMID- 26561544 TI - Reply: Maternal and neonatal outcomes in women diagnosed with PCOS by different definitions. PMID- 26561545 TI - IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity. AB - IL-1R-associated kinase (IRAK) 1 is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. In this study, we show that IRAK1 promotes Th17 development by mediating IL-1beta-induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts regulatory T cell generation. Cotransfer experiments revealed that Irak1-deficient CD4(+) T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes, and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mesenteric lymph nodes. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of alpha4beta7 integrin after transfer into Rag1(-/-) mice, and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation, and accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases. PMID- 26561546 TI - Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression. AB - Although there is great interest in harnessing the immunosuppressive potential of FOXP3(+) regulatory T cells (Tregs) for treating autoimmunity, a sizeable knowledge gap exists regarding Treg fate in human disease. In juvenile idiopathic arthritis (JIA) patients, we have previously reported that atypical CD25(+)FOXP3( ) Treg-like cells uniquely populate the inflamed site. Intriguingly, their proportions relative to CD25(+)FOXP3(+) Tregs associate with arthritis course, suggesting a role in disease. The ontogeny of these FOXP3(-) Treg-like cells is, however, unknown. In this study, we interrogated clonal relationships between CD4(+) T cell subsets in JIA, using high-throughput TCR repertoire analysis. We reveal that FOXP3(+) Tregs possess highly exclusive TCRbeta usage from conventional T cells, in blood, and also at the inflamed site, where they are clonally expanded. Intriguingly, the repertoires of FOXP3(+) Tregs in synovial fluid are highly overlapping with CD25(+)FOXP3(-) Treg-like cells, indicating fluctuations in FOXP3 expression in the inflamed joint. Furthermore, cultured synovial Tregs rapidly downregulated FOXP3 protein (but not mRNA), and this process was prevented by addition of synovial fluid from JIA patients, through an IL-6-independent mechanism. Our findings suggest that most Tregs arise from a separate lineage from conventional T cells, and that this repertoire divergence is largely maintained under chronic inflammatory conditions. We propose that subsequent Treg expansions at the inflamed site creates an environment that leads to competition for limited resources within the synovium, resulting in the destabilization of FOXP3 expression in some Tregs. PMID- 26561547 TI - FOXO3-NF-kappaB RelA Protein Complexes Reduce Proinflammatory Cell Signaling and Function. AB - Tumor-associated myeloid cells, including dendritic cells (DCs) and macrophages, are immune suppressive. This study demonstrates a novel mechanism involving FOXO3 and NF-kappaB RelA that controls myeloid cell signaling and impacts their immune suppressive nature. We find that FOXO3 binds NF-kappaB RelA in the cytosol, impacting both proteins by preventing FOXO3 degradation and preventing NF-kappaB RelA nuclear translocation. The location of protein-protein interaction was determined to be near the FOXO3 transactivation domain. In turn, NF-kappaB RelA activation was restored upon deletion of the same sequence in FOXO3 containing the DNA binding domain. We have identified for the first time, to our knowledge, a direct protein-protein interaction between FOXO3 and NF-kappaB RelA in tumor associated DCs. These detailed biochemical interactions provide the foundation for future studies to use the FOXO3-NF-kappaB RelA interaction as a target to enhance tumor-associated DC function to support or enhance antitumor immunity. PMID- 26561549 TI - Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating. AB - The abortion-prone mating combination CBA/J * DBA/2 has been recognized as a model of preeclampsia, and complement activation has been implicated in the high rate of pregnancy loss observed in CBA/J mice. We have analyzed the implantation sites collected from DBA/2-mated CBA/J mice for the deposition of the complement recognition molecules using CBA/J mated with BALB/c mice as a control group. MBL A was observed in the implantation sites of CBA/J * DBA/2 combination in the absence of MBL-C and was undetectable in BALB/c-mated CBA/J mice. Conversely, C1q was present in both mating combinations. Searching for other complement components localized at the implantation sites of CBA/J * DBA/2, we found C4 and C3, but we failed to reveal C1r. These data suggest that complement is activated through the lectin pathway and proceeds to completion of the activation sequence as revealed by C9 deposition. MBL-A was detected as early as 3.5 d of pregnancy, and MBL-A deficiency prevented pregnancy loss in the abortion-prone mating combination. The contribution of the terminal complex to miscarriage was supported by the finding that pregnancy failure was largely inhibited by the administration of neutralizing Ab to C5. Treatment of DBA/2-mated CBA/J mice with Polyman2 that binds to MBL-A with high affinity proved to be highly effective in controlling the activation of the lectin pathway and in preventing fetal loss. PMID- 26561548 TI - Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells. AB - Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-beta1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen induced inflammation by modulating MSC recruitment and their immune-suppressive activity. PMID- 26561550 TI - Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice. AB - Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases. PMID- 26561552 TI - Calcium-Modulating Cyclophilin Ligand Is Essential for the Survival of Activated T Cells and for Adaptive Immunity. AB - Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum resident protein that is widely expressed. Although it has been demonstrated to participate in the tail-anchored protein insertion pathway, its physiological role in the mature immune system is unknown. In this work, we show that mature, peripheral T cells require CAML for survival specifically following TCR-induced activation. In this study, we examined mature T cells from spleen and lymph nodes of tamoxifen-inducible CAML knockout mice (tCAML(-/-)). Whereas CAML-deficient T cells were able to express the early activation markers CD25 and CD69, and produce IL-2 normally upon stimulation, deficient cells proliferated less and died. Cells did not require CAML for entry into the S phase of the cell cycle, thus implicating its survival function at a relatively late step in the T cell activation sequence. In addition, CAML was required for homeostatic proliferation and for Ag-dependent cell killing in vivo. These results demonstrate that CAML critically supports T cell survival and cell division downstream of T cell activation. PMID- 26561551 TI - Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules. AB - Triggering receptor expressed on myeloid cells-1 (TREM-1) is critical for inflammatory signal amplification. Humans have two forms of TREM-1: a membrane receptor, associated with the adaptor DAP12, and a soluble receptor detected at times of infection. The membrane receptor isoform acts synergistically with the TLR pathway to promote cytokine secretion and neutrophil migration, whereas the soluble receptor functions as a counterregulatory molecule. In multiple models of sepsis, exogenous administration of soluble forms of TREM-1 attenuates inflammation and markedly improves survival. Despite intense interest in soluble TREM-1, both as a clinical predictor of survival and as a therapeutic tool, the origin of native soluble TREM-1 remains controversial. Using human neutrophils, we identified a 15-kDa TREM-1 isoform in primary (azurophilic) and secondary (specific) granules. Mass spectrometric analysis, ELISA, and immunoblot confirm that the 15-kDa protein is a novel splice variant form of TREM-1 (TREM-1sv). Neutrophil stimulation with Pseudomonas aeruginosa, LPS, or PAM(3)Cys4 resulted in degranulation and release of TREM-1sv. The addition of exogenous TREM-1sv inhibited TREM-1 receptor-mediated proinflammatory cytokine production. Thus, these data reveal that TREM-1 isoforms simultaneously activate and inhibit inflammation via the canonical membrane TREM-1 molecule and this newly discovered granular isoform, TREM-1sv. PMID- 26561554 TI - Improving the recognition and diagnosis of opioid-induced constipation in clinical practice. AB - Opioid-induced constipation is a common side effect of opioid therapy that has been under-recognized and undertreated. With the continued increase in opioid use in the United States, along with the growth of the elderly population, more patients will develop OIC, and family physicians will encounter more patients with OIC. OIC negatively affects patient QOL, daily activity, work productivity, and psychological well-being. If not treated effectively, OIC may result in patients attempting to balance their pain relief against their constipation, by self-adjusting their opioid dose. OIC results from opioid actions at enteric opioid receptors. Although commonly prescribed for OIC, laxatives do not target the pathophysiologic mechanism of OIC and have limited efficacy. Specific, effective treatments for OIC, consisting of a subcutaneously administered PAMORA, an oral PAMORA, and an oral chloride channel activator, have been developed and have received US Food and Drug Administration approval. After recognizing the signs and symptoms of OIC to facilitate diagnosis, family physicians can initiate effective treatments in appropriate patients. PMID- 26561553 TI - Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy. AB - The ability of immune-based cancer therapies to elicit beneficial CD8(+) CTLs is limited by tolerance pathways that inactivate tumor-specific CD4 Th cells. A strategy to bypass this problem is to engage tumor-unrelated CD4 Th cells. Thus, CD4 T cells, regardless of their specificity per se, can boost CD8(+) CTL priming as long as the cognate epitopes are linked via presentation on the same dendritic cell. In this study, we assessed the therapeutic impact of engaging tumor unrelated CD4 T cells during dual costimulation with CD134 plus CD137 that provide help via the above-mentioned classical linked pathway, as well as provide nonlinked help that facilitates CTL function in T cells not directly responding to cognate Ag. We found that engagement of tumor-unrelated CD4 Th cells dramatically boosted the ability of dual costimulation to control the growth of established B16 melanomas. Surprisingly, this effect depended upon a CD134 dependent component that was extrinsic to the tumor-unrelated CD4 T cells, suggesting that the dual costimulated helper cells are themselves helped by a CD134(+) cell(s). Nevertheless, the delivery of therapeutic help tracked with an increased frequency of tumor-infiltrating granzyme B(+) effector CD8 T cells and a reciprocal decrease in Foxp3(+)CD4(+) cell frequency. Notably, the tumor unrelated CD4 Th cells also infiltrated the tumors, and their deletion several days following initial T cell priming negated their therapeutic impact. Taken together, dual costimulation programs tumor-unrelated CD4 T cells to deliver therapeutic help during both the priming and effector stages of the antitumor response. PMID- 26561555 TI - e-CBT (myCompass), Antidepressant Medication, and Face-to-Face Psychological Treatment for Depression in Australia: A Cost-Effectiveness Comparison. AB - BACKGROUND: The economic cost of depression is becoming an ever more important determinant for health policy and decision makers. Internet-based interventions with and without therapist support have been found to be effective options for the treatment of mild to moderate depression. With increasing demands on health resources and shortages of mental health care professionals, the integration of cost-effective treatment options such as Internet-based programs into primary health care could increase efficiency in terms of resource use and costs. OBJECTIVE: Our aim was to evaluate the cost-effectiveness of an Internet-based intervention (myCompass) for the treatment of mild-to-moderate depression compared to treatment as usual and cognitive behavior therapy in a stepped care model. METHODS: A decision model was constructed using a cost utility framework to show both costs and health outcomes. In accordance with current treatment guidelines, a stepped care model included myCompass as the first low-intervention step in care for a proportion of the model cohort, with participants beginning from a low-intensity intervention to increasing levels of treatment. Model parameters were based on data from the recent randomized controlled trial of myCompass, which showed that the intervention reduced symptoms of depression, anxiety, and stress and improved work and social functioning for people with symptoms in the mild-to-moderate range. RESULTS: The average net monetary benefit (NMB) was calculated, identifying myCompass as the strategy with the highest net benefit. The mean incremental NMB per individual for the myCompass group was AUD 1165.88 compared to treatment as usual and AUD 522.58 for the cognitive behavioral therapy model. CONCLUSIONS: Internet-based interventions can provide cost-effective access to treatment when provided as part of a stepped care model. Widespread dissemination of Internet-based programs can potentially reduce demands on primary and tertiary services and reduce unmet need. PMID- 26561556 TI - Different clinical outcomes between locally advanced hypopharyngeal and oropharyngeal cancer treated with definitive concurrent chemoradiotherapy: implication for subgroup selection for induction chemotherapy. AB - OBJECTIVE: The purpose of this study is to compare the long-term clinical outcome of hypopharynx cancer and oropharynx cancer treated with concurrent chemoradiotherapy. METHODS: A total of 213 patients with locally advanced hypopharyngeal squamous cell carcinoma (n = 79) or oropharygeal squamous cell carcinoma (n = 134) were included. All patients were treated with upfront concurrent chemoradiotherapy between 1995 and 2012. RESULTS: The median overall survival and progression-free survival differed significantly between the two groups (P < 0.05). Overall survival and progression-free survival rates at 3 years were 52% and 42% for hypopharynx cancer, and 75% and 72% for oropharynx cancer, respectively. There was no significant difference in the overall incidence of distant metastases but more locoregional recurrences occurred in patients with hypopharynx cancer compared with those with oropharynx cancer with a statistical significance (P < 0.001). CONCLUSIONS: Patients diagnosed with locally advanced hypopharyngeal had relatively poor survival after upfront concurrent chemoradiotherapy. More intensive treatment such as induction chemotherapy before concurrent chemoradiotherapy might be needed to improve survival outcome in this subgroup of patients. PMID- 26561557 TI - Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting. AB - PURPOSE: In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. EXPERIMENTAL DESIGN: We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. RESULTS: AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. CONCLUSIONS: Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood based test for early detection of colorectal cancer. PMID- 26561558 TI - InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma. AB - PURPOSE: Aberrant activation of EGFR is a hallmark of glioblastoma. However, EGFR inhibitors exhibit at best modest efficacy in glioblastoma. This is in sharp contrast with the observations in EGFR-mutant lung cancer. We examined whether activation of functionally redundant receptor tyrosine kinases (RTKs) conferred resistance to EGFR inhibitors in glioblastoma. EXPERIMENTAL DESIGN: We collected a panel of patient-derived glioblastoma xenograft (PDX) lines that maintained expression of wild-type or mutant EGFR in serial xenotransplantation and tissue cultures. Using this physiologically relevant platform, we tested the abilities of several RTK ligands to protect glioblastoma cells against an EGFR inhibitor, gefitinib. Based on the screening results, we further developed a combination therapy cotargeting EGFR and insulin receptor (InsR)/insulin-like growth factor 1 receptor (IGF1R). RESULTS: Insulin and IGF1 induced significant protection against gefitinib in the majority of EGFR-dependent PDX lines with one exception that did not express InsR or IGF1R. Blockade of the InsR/IGF1R pathway synergistically improved sensitivity to gefitinib or dacomitinib. Gefitinib alone effectively attenuated EGFR activities and the downstream MEK/ERK pathway. However, repression of AKT and induction of apoptosis required concurrent inhibition of both EGFR and InsR/IGF1R. A combination of gefitinib and OSI-906, a dual InsR/IGF1R inhibitor, was more effective than either agent alone to treat subcutaneous glioblastoma xenograft tumors. CONCLUSIONS: Our results suggest that activation of the InsR/IGF1R pathway confers resistance to EGFR inhibitors in EGFR-dependent glioblastoma through AKT regulation. Concurrent blockade of these two pathways holds promise to treat EGFR-dependent glioblastoma. PMID- 26561560 TI - Revealing the Elusive Plant Epitranscriptome. PMID- 26561559 TI - Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma. AB - PURPOSE: Evaluate the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of the first-in-class investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924) in patients with relapsed/refractory lymphoma or multiple myeloma. EXPERIMENTAL DESIGN: Patients with relapsed/refractory myeloma (n = 17) or lymphoma (n = 27) received intravenous pevonedistat 25 to 147 mg/m(2) on days 1, 2, 8, 9 (schedule A; n = 27) or 100 to 261 mg/m(2) on days 1, 4, 8, 11 (schedule B; n = 17) of 21-day cycles. RESULTS: Maximum tolerated doses were 110 mg/m(2) (schedule A) and 196 mg/m(2) (schedule B). Dose-limiting toxicities included febrile neutropenia, transaminase elevations, muscle cramps (schedule A), and thrombocytopenia (schedule B). Common adverse events included fatigue and nausea. Common grade >=3 events were anemia (19%; schedule A), and neutropenia and pneumonia (12%; schedule B). Clinically significant myelosuppression was uncommon. There were no treatment-related deaths. Pevonedistat pharmacokinetics exhibited a biphasic disposition phase and approximate dose-proportional increases in systemic exposure. Consistent with the short mean elimination half-life of approximately 8.5 hours, little-to-no drug accumulation in plasma was seen after multiple dosing. Pharmacodynamic evidence of NAE inhibition included increased skin levels of CDT-1 and NRF-2 (substrates of NAE-dependent ubiquitin ligases), and increased NRF-2-regulated gene transcript levels in whole blood. Pevonedistat-NEDD8 adduct was detected in bone marrow aspirates, indicating pevonedistat target engagement in the bone marrow compartment. Three lymphoma patients had partial responses; 30 patients achieved stable disease. CONCLUSIONS: Pevonedistat demonstrated anticipated pharmacodynamic effects in the clinical setting, a tolerable safety profile, and some preliminary evidence that may be suggestive of the potential for activity in relapsed/refractory lymphoma. PMID- 26561561 TI - Chemical Modifications Mark Alternatively Spliced and Uncapped Messenger RNAs in Arabidopsis. AB - Posttranscriptional chemical modification of RNA bases is a widespread and physiologically relevant regulator of RNA maturation, stability, and function. While modifications are best characterized in short, noncoding RNAs such as tRNAs, growing evidence indicates that mRNAs and long noncoding RNAs (lncRNAs) are likewise modified. Here, we apply our high-throughput annotation of modified ribonucleotides (HAMR) pipeline to identify and classify modifications that affect Watson-Crick base pairing at three different levels of the Arabidopsis thaliana transcriptome (polyadenylated, small, and degrading RNAs). We find this type of modifications primarily within uncapped, degrading mRNAs and lncRNAs, suggesting they are the cause or consequence of RNA turnover. Additionally, modifications within stable mRNAs tend to occur in alternatively spliced introns, suggesting they regulate splicing. Furthermore, these modifications target mRNAs with coherent functions, including stress responses. Thus, our comprehensive analysis across multiple RNA classes yields insights into the functions of covalent RNA modifications in plant transcriptomes. PMID- 26561562 TI - The effect and mechanism of electroacupuncture at LI11 and ST37 on constipation in a rat model. AB - BACKGROUND: Electroacupuncture (EA) is used clinically for the treatment of constipation. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in colonic motility; however it is unknown whether alterations in colonic 5-HT are associated with EA. In this study, the effect and mechanism of EA at acupuncture points LI11 and ST37 were examined using a cold saline-induced rat model of constipation. METHODS: A rat constipation model was induced by cold saline gavage in 24 Sprague-Dawley rats. A further six rats were included as a Control group. The constipated rats were divided into four groups (n=6 each): a Constipation group that remained untreated; a Constipation+LI11 group that received EA at LI11; a Constipation+ST37 groups that received EA at ST37; and a Constipation+LI11+ST37 group that received EA at both LI11 and ST37. After EA treatment, faecal water content, defaecation frequency, and gastrointestinal (GI) transit were measured, as well as the expression of tryptophan hydroxylase (TPH) in colonic tissues (by Western blot analysis) and 5-HT in both faeces and colonic tissues (by ELISA). RESULTS: All three EA-treated groups demonstrated significant improvements in faecal water content, defaecation frequency and GI transit (p<0.05). In addition, TPH and 5-HT expression were both increased by EA at LI11 and/or ST37 (p<0.05). There were no significant differences between the three EA groups for any outcomes. CONCLUSIONS: EA at LI11 and/or ST37 had a positive effect on objective markers of constipation in a rat model. In addition, EA increased 5-HT and TPH in the colonic tissues. PMID- 26561564 TI - Differential Roles of Two Homologous Cyclin-Dependent Kinase Inhibitor Genes in Regulating Cell Cycle and Innate Immunity in Arabidopsis. AB - Precise cell-cycle control is critical for plant development and responses to pathogen invasion. Two homologous cyclin-dependent kinase inhibitor genes, SIAMESE (SIM) and SIM-RELATED 1 (SMR1), were recently shown to regulate Arabidopsis (Arabidopsis thaliana) defense based on phenotypes conferred by a sim smr1 double mutant. However, whether these two genes play differential roles in cell-cycle and defense control is unknown. In this report, we show that while acting synergistically to promote endoreplication, SIM and SMR1 play different roles in affecting the ploidy of trichome and leaf cells, respectively. In addition, we found that the smr1-1 mutant, but not sim-1, was more susceptible to a virulent Pseudomonas syringae strain, and this susceptibility could be rescued by activating salicylic acid (SA)-mediated defense. Consistent with these results, smr1-1 partially suppressed the dwarfism, high SA levels, and cell death phenotypes in acd6-1, a mutant used to gauge the change of defense levels. Thus, SMR1 functions partly through SA in defense control. The differential roles of SIM and SMR1 are due to differences in temporal and spatial expression of these two genes in Arabidopsis tissues and in response to P. syringae infection. In addition, flow-cytometry analysis of plants with altered SA signaling revealed that SA is necessary, but not sufficient, to change cell-cycle progression. We further found that a mutant with three CYCD3 genes disrupted also compromised disease resistance to P. syringae. Together, this study reveals differential roles of two homologous cyclin-dependent kinase inhibitors in regulating cell cycle progression and innate immunity in Arabidopsis and provides insights into the importance of cell-cycle control during host-pathogen interactions. PMID- 26561566 TI - Clinical Efficacy of Thrombus Aspiration on 5-Year Clinical Outcomes in Patients With ST-Segment Elevation Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention. PMID- 26561565 TI - Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding. AB - Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward. PMID- 26561567 TI - Dual inhibition of histone deacetylases and phosphoinositide 3-kinases: effects on Burkitt lymphoma cell growth and migration. AB - Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high-dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell-cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of alpha-tubulin and the regulation of RhoB expression. PMID- 26561568 TI - ADAM17 controls IL-6 signaling by cleavage of the murine IL-6Ralpha from the cell surface of leukocytes during inflammatory responses. AB - The cytokine IL-6 is part of a regulatory signaling network that controls immune responses. IL-6 binds either to the membrane-bound IL-6 receptor-alpha (classic signaling) or to the soluble IL-6 receptor-alpha (trans-signaling) to initiate signal transduction via gp130 activation. Because classic and trans-signaling of IL-6 fulfill different tasks during immune responses, controlled shedding of the membrane-bound IL-6 receptor-alpha from the surface of immune cells can be considered a central regulator of IL-6 function. The results from cell culture based experiments have implicated both a disintegrin and metalloprotease 10 and a disintegrin and metalloprotease 17 in IL-6 receptor-alpha shedding. However, the nature of the protease mediating IL-6 receptor-alpha release in vivo is not yet known. We used hypomorphic a disintegrin and metalloprotease 17 mice and conditional a disintegrin and metalloprotease 10 knock-out mice to identify the natural protease of the murine IL-6 receptor-alpha. Circulating homeostatic soluble IL-6 receptor-alpha levels are not dependent on a disintegrin and metalloprotease 10 or 17 activity. However, during Listeria monocytogenes infection, IL-6 receptor-alpha cleavage by the alpha-secretase a disintegrin and metalloprotease 17 is rapidly induced from the surface of different leukocyte populations. In contrast, CD4-Cre-driven a disintegrin and metalloprotease 10 deletion in T cells did not influence IL-6 receptor-alpha shedding from these cells after L. monocytogenes infection. A disintegrin and metalloprotease 17 was also required for IL-6 receptor-alpha ectodomain cleavage and release during endotoxemia. These results demonstrate a novel physiologic role for a disintegrin and metalloprotease 17 in regulating murine IL-6 signals during inflammatory processes. PMID- 26561569 TI - Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vgamma9Vdelta2 T cells in low levels of IL-2. AB - Human gammadelta T cells play important roles in the regulation of infection and cancer. To understand the roles of costimulatory signals in activation and expansion ex vivo, Vgamma9Vdelta2 T cells were grown with artificial APCs that express CD83, 4-1BB ligand, and/or CD32, which allowed a loading of alphaCD3 and alphaCD28 antibodies. The costimulatory signals through CD80, 4-1BB, and CD83 ligand in low levels of IL-2 triggered an explosive ex vivo proliferation of Vgamma9Vdelta2 T cells capable of secreting high levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, the triple-costimulatory signals cause augmented cell viabilities for long-term growth of Vgamma9Vdelta2 T cells, resulting in phenotypic changes to CD27(-)CD45RA(+) effector memory-like cells. Notably, we observed that CD83 ligand signaling is crucial to promote ex vivo expansion, survival, and cytolytic effector functions of Vgamma9Vdelta2 T cells. In contrast, 4-1BB signaling is moderately important in up-regulating surface molecules on Vgamma9Vdelta2 T cells. Consequently, gammadelta T cells stimulated in the presence of triple-costimulatory signals have diverse cytolytic effector molecules, including perforin, granzyme A, granzyme B, and Fas ligand, eliciting potent cytolytic activities against tumor cells. Overall, our results provide insights into the roles of costimulatory signals in manufacturing long-lived and fully functional Vgamma9Vdelta2 T cells that could be useful against cancers. PMID- 26561571 TI - Spatio-temporal control of cellular uptake achieved by photoswitchable cell penetrating peptides. AB - The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control. PMID- 26561570 TI - Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. AB - BACKGROUND: Infantile-onset encephalopathy and hypertrophic cardiomyopathy caused by mitochondrial oxidative phosphorylation defects are genetically heterogeneous with defects involving both the mitochondrial and nuclear genomes. OBJECTIVE: To identify the causative genetic defect in two sisters presenting with lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. METHODS: We describe a comprehensive clinical, biochemical and molecular genetic investigation of two affected siblings from a consanguineous family. Molecular genetic analysis was done by a combined approach involving genome-wide autozygosity mapping and next-generation exome sequencing. Biochemical analysis was done by enzymatic analysis and Western blot. Evidence for mitochondrial DNA (mtDNA) instability was investigated using long-range and real-time PCR assays. Mitochondrial cristae morphology was assessed with transmission electron microscopy. RESULTS: Both affected sisters presented with a similar cluster of neurodevelopmental deficits marked by failure to thrive, generalised neuromuscular weakness and optic atrophy. The disease progression was ultimately fatal with severe encephalopathy and hypertrophic cardiomyopathy. Mitochondrial respiratory chain complex activities were globally decreased in skeletal muscle biopsies. They were found to be homozygous for a novel c.1601T>G (p.Leu534Arg) mutation in the OPA1 gene, which resulted in a marked loss of steady-state levels of the native OPA1 protein. We observed severe mtDNA depletion in DNA extracted from the patients' muscle biopsies. Mitochondrial morphology was consistent with abnormal mitochondrial membrane fusion. CONCLUSIONS: We have established, for the first time, a causal link between a pathogenic homozygous OPA1 mutation and human disease. The fatal multisystemic manifestations observed further extend the complex phenotype associated with pathogenic OPA1 mutations, in particular the previously unreported association with hypertrophic cardiomyopathy. Our findings further emphasise the vital role played by OPA1 in mitochondrial biogenesis and mtDNA maintenance. PMID- 26561573 TI - Peer-Review Responsibility. PMID- 26561572 TI - Azeotropic drying free [(18)F]FDG synthesis and its application to a lab-on-chip platform. AB - A very simple and time-saving cartridge-based drying technique for [(18)F]fluoride allows for an efficient [(18)F]FDG synthesis using protic solvents and high water content. This novel method has been adapted to a lab-on chip synthesis platform mitigating the standard azeotropic drying process and demonstrating a proof of concept towards reduced hardware complexity for such systems. PMID- 26561574 TI - Letter to the Editor. PMID- 26561576 TI - From simplicity to complex systems with bioinspired pseudopeptides. AB - Pseudopeptidic compounds are chemical species with attractive applications in many fields of chemistry. The increasing complexity in pseudopeptidic molecules has allowed improvements of their properties, very often after an initial bio inspiration. Two main types of complexity can be proposed: structural and interactional. These operational processes have recently been used for the generation of new elaborated pseudopetidic molecules and complex molecular systems. This feature article presents a brief discussion of the recent advances done following this rational and with these privileged molecules. PMID- 26561577 TI - Triplet energy management between two signaling units through cooperative rigid scaffolds. AB - Through-bond triplet exciplex formation in donor-acceptor systems linked through a rigid bile acid scaffold has been demonstrated on the basis of kinetic evidence upon population of the triplet acceptors (naphthalene, or biphenyl) by through bond triplet-triplet energy transfer from benzophenone. PMID- 26561578 TI - Olfactory variation in mouse husbandry and its implications for refinement and standardization: UK survey of non-animal scents. AB - With their highly sensitive olfactory system, the behaviour and physiology of mice are not only influenced by the scents of conspecifics and other species, but also by many other chemicals in the environment. The constraints of laboratory housing limit a mouse's capacity to avoid aversive odours that could be present in the environment. Potentially odorous items routinely used for husbandry procedures, such as sanitizing products and gloves, could be perceived by mice as aversive or attractive, and affect their behaviour, physiology and experimental results. A survey was sent to research institutions in the UK to enquire about husbandry practices that could impact on the olfactory environment of the mouse. Responses were obtained from 80 individuals working in 51 institutions. Husbandry practices varied considerably. Seventy percent of respondents reported always wearing gloves for handling mice, with nitrile being the most common glove material (94%) followed by latex (23%) and vinyl (14%). Over six different products were listed for cleaning surfaces, floors, anaesthesia and euthanasia chambers and behavioural apparatus. In all cases TrigeneTM (now called AnistelTM) was the most common cleaning product used (43, 41, 40 and 49%, respectively). Depending on the attribute considered, between 7 and 19% of respondents thought that cleaning products definitely, or were likely to, have strong effects on standardization, mouse health, physiology or behaviour. Understanding whether and how these odours affect mouse welfare will help to refine mouse husbandry and experimental procedures through practical recommendations, to improve the quality of life of laboratory animals and the experimental data obtained. PMID- 26561579 TI - Improved synthesis of trigone trimer cluster metal organic framework MIL-100Al by a later entry of methyl groups. AB - Later entry of methyl or ethyl groups was carried out for the economical synthesis of trigone trimer cluster MIL-100Al oriented from H3BTC directly. The pure phase MIL-100Al was obtained in a DMF aqueous solution, and equal amounts of methyl and carboxyl groups are the key for the successful synthesis of MIL-100Al. PMID- 26561580 TI - Topological mechanics of gyroscopic metamaterials. AB - Topological mechanical metamaterials are artificial structures whose unusual properties are protected very much like their electronic and optical counterparts. Here, we present an experimental and theoretical study of an active metamaterial--composed of coupled gyroscopes on a lattice--that breaks time reversal symmetry. The vibrational spectrum displays a sonic gap populated by topologically protected edge modes that propagate in only one direction and are unaffected by disorder. We present a mathematical model that explains how the edge mode chirality can be switched via controlled distortions of the underlying lattice. This effect allows the direction of the edge current to be determined on demand. We demonstrate this functionality in experiment and envision applications of these edge modes to the design of one-way acoustic waveguides. PMID- 26561581 TI - Extremely high genetic diversity in a single tumor points to prevalence of non Darwinian cell evolution. AB - The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 "polymorphic" SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non Darwinian evolution should be heeded in cancer treatments even for microscopic tumors. PMID- 26561582 TI - Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme. AB - A long-standing contradiction in the field of mononuclear Mo enzyme research is that small-molecule chemistry on active-site mimic compounds predicts ligand participation in the electron transfer reactions, but biochemical measurements only suggest metal-centered catalytic electron transfer. With the simultaneous measurement of substrate turnover and reversible electron transfer that is provided by Fourier-transformed alternating-current voltammetry, we show that Escherichia coli YedY is a mononuclear Mo enzyme that reconciles this conflict. In YedY, addition of three protons and three electrons to the well-characterized "as-isolated" Mo(V) oxidation state is needed to initiate the catalytic reduction of either dimethyl sulfoxide or trimethylamine N-oxide. Based on comparison with earlier studies and our UV-vis redox titration data, we assign the reversible one proton and one-electron reduction process centered around +174 mV vs. standard hydrogen electrode at pH 7 to a Mo(V)-to-Mo(IV) conversion but ascribe the two proton and two-electron transition occurring at negative potential to the organic pyranopterin ligand system. We predict that a dihydro-to-tetrahydro transition is needed to generate the catalytically active state of the enzyme. This is a previously unidentified mechanism, suggested by the structural simplicity of YedY, a protein in which Mo is the only metal site. PMID- 26561583 TI - Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes. AB - During meiosis, homologous chromosomes associate to form the synaptonemal complex (SC), a structure essential for fertility. Information about the epigenetic features of chromatin within this structure at the level of superresolution microscopy is largely lacking. We combined single-molecule localization microscopy (SMLM) with quantitative analytical methods to describe the epigenetic landscape of meiotic chromosomes at the pachytene stage in mouse oocytes. DNA is found to be nonrandomly distributed along the length of the SC in condensed clusters. Periodic clusters of repressive chromatin [trimethylation of histone H3 at lysine (Lys) 27 (H3K27me3)] are found at 500-nm intervals along the SC, whereas one of the ends of the SC displays a large and dense cluster of centromeric histone mark [trimethylation of histone H3 at Lys 9 (H3K9me3)]. Chromatin associated with active transcription [trimethylation of histone H3 at Lys 4 (H3K4me3)] is arranged in a radial hair-like loop pattern emerging laterally from the SC. These loops seem to be punctuated with small clusters of H3K4me3 with an average spread larger than their periodicity. Our findings indicate that the nanoscale structure of the pachytene chromosomes is constrained by periodic patterns of chromatin marks, whose function in recombination and higher order genome organization is yet to be elucidated. PMID- 26561585 TI - Universal spectrum of normal modes in low-temperature glasses. AB - We report an analytical study of the vibrational spectrum of the simplest model of jamming, the soft perceptron. We identify two distinct classes of soft modes. The first kind of modes are related to isostaticity and appear only in the close vicinity of the jamming transition. The second kind of modes instead are present everywhere in the glass phase and are related to the hierarchical structure of the potential energy landscape. Our results highlight the universality of the spectrum of normal modes in disordered systems, and open the way toward a detailed analytical understanding of the vibrational spectrum of low-temperature glasses. PMID- 26561584 TI - An extracatalytic function of CD45 in B cells is mediated by CD22. AB - The receptor-like tyrosine phosphatase CD45 regulates antigen receptor signaling by dephosphorylating the C-terminal inhibitory tyrosine of the src family kinases. However, despite its abundance, the function of the large, alternatively spliced extracellular domain of CD45 has remained elusive. We used normally spliced CD45 transgenes either incorporating a phosphatase-inactivating point mutation or lacking the cytoplasmic domain to uncouple the enzymatic and noncatalytic functions of CD45 in lymphocytes. Although these transgenes did not alter T-cell signaling or development irrespective of endogenous CD45 expression, both partially rescued the phenotype of CD45-deficient B cells. We identify a noncatalytic role for CD45 in regulating tonic, but not antigen-mediated, B-cell antigen receptor (BCR) signaling through modulation of the function of the inhibitory coreceptor CD22. This finding has important implications for understanding how naive B cells maintain tonic BCR signaling while restraining inappropriate antigen-dependent activation to preserve clonal "ignorance." PMID- 26561587 TI - Chemotherapy regimen checks performed by pharmacists contribute to safe administration of chemotherapy. AB - Background Computerized provider order entry (CPOE) has been developed and implemented within cancer center hospitals nationwide in Japan. To ensure that high-quality services are routinely provided by oncology pharmacists, this study was designed to evaluate the interventions through reviewing the orders that are generated by CPOE. Methods The objective of this retrospective chart review was to evaluate how pharmacists contributed to safe cancer treatment using paper based pharmacy records. Data were collected from a total of 35,062 chemotherapy regimens for 18,515 outpatients between January and December 2013. Results Of these 35,062 chemotherapy regimens, the rate of pharmacists' interventions was 1.1% ( n = 408). Among them, 53.1% (217/408) of the chemotherapy prescriptions were modified due to pharmacist interventions. The reasons for interventions included "changes in the chemotherapy regimen were unclear" in 49.5%, "physicians' prescription errors" (22.0%), "pharmacist suggestions to improve chemotherapy" (15.1%), and "finding differences between physicians' chemotherapy records and their chemotherapy prescriptions" (13.2%). The top three reasons for the 217 prescription modifications due to pharmacist interventions were "finding prescription errors" (34.5%), "reasons for change in the chemotherapy regimen were unclear" (32.7%), and "finding differences between physicians' chemotherapy records and their chemotherapy prescriptions" (28.5%). Conclusion The computer could not evaluate chemotherapy protocols or adjust doses of anticancer medicines according to patients' conditions. Therefore, oncology pharmacists should continue to ensure safe and appropriate administration of cancer chemotherapy. PMID- 26561586 TI - Dendritic cells require NIK for CD40-dependent cross-priming of CD8+ T cells. AB - Dendritic cells (DCs) link innate and adaptive immunity and use a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. Although DC maturation via canonical NF-kappaB signaling is critical for many of these functions, the role of noncanonical NF-kappaB signaling via the serine/threonine kinase NIK (NF-kappaB-inducing kinase) remains unclear. Because NIK-deficient mice lack secondary lymphoid organs, we generated transgenic mice with targeted NIK deletion in CD11c(+) cells. Although these mice exhibited normal lymphoid organs, they were defective in cross-priming naive CD8(+) T cells following vaccination, even in the presence of anti-CD40 or polyinosinic:polycytidylic acid to induce DC maturation. This impairment reflected two intrinsic defects observed in splenic CD8(+) DCs in vitro, namely antigen cross-presentation to CD8(+) T cells and secretion of IL-12p40, a cytokine known to promote cross-priming in vivo. In contrast, antigen presentation to CD4(+) T cells was not affected. These findings reveal that NIK, and thus probably the noncanonical NF-kappaB pathway, is critical to allow DCs to acquire the capacity to cross-present antigen and prime CD8 T cells after exposure to licensing stimuli, such as an agonistic anti-CD40 antibody or Toll like receptor 3 ligand. PMID- 26561588 TI - Cross-cultural validation of the Prosthesis Evaluation Questionnaire in vascular amputees fitted with prostheses in Spain. AB - BACKGROUND: The lack of specific prosthetic-related outcome instruments for Spanish amputees must be addressed. OBJECTIVE: To elaborate a culturally equivalent version of the Prosthesis Evaluation Questionnaire in the Spanish language. STUDY DESIGN: Cross-cultural questionnaire validation. METHODS: Two step process for cultural adaptation: forward and backward translations of English original and Spanish translated versions; assessment of both construct and criterion validity and reliability in a group of vascular amputees. RESULTS: A total of 61 patients were recruited, 44 men (72.1%) and 17 women (27.9%), with a median age of 71.1 years (standard deviation: 7.7 years; range: 51-87 years). In the Prosthesis Evaluation Questionnaire-Spanish, the lowest scores were for gait and frustration, and the highest scores were for noise and stump health. Internal consistency of the questionnaire was acceptable (>0.70) for four of the scales used in the Prosthesis Evaluation Questionnaire but poor (<0.50) for the scales relating to appearance and stump health. Correlations with the quality-of life levels as measured by the Short Form-36 were positive and mostly significant. CONCLUSION: Prosthesis Evaluation Questionnaire-Spanish could assess the quality of life in patients who have undergone vascular amputations and then been fitted with a prosthetic limb. The questionnaire shows adequate criteria validity when compared with other instruments for measuring quality of life. CLINICAL RELEVANCE: The Prosthesis Evaluation Questionnaire-Spanish could be a valid and reliable instrument for assessing adaptation to prostheses in vascular amputees. The questionnaire adds information relevant to the patient and the physician and may identify cases with poor expected adaptation to the prosthesis. PMID- 26561589 TI - 'Normal' serum sodium concentration among inpatients over 65 admitted to hospital: an observational study. AB - BACKGROUND: The usual reference range of serum sodium (typically 135-145 mmol/l) is derived from healthy populations but may not apply to hospital patients. OBJECTIVES: To describe the range of serum sodium in inpatients and outpatients of both sexes at different ages. To ascertain correlates of serum sodium among older inpatients. To describe the association between sodium and mortality. METHODS: We used routine hospital data on serum sodium in inpatients admitted between 1 January 2011 and 31 December 2014 and patients attending outpatient or community clinics with no record of admission to the same hospitals in the same period. We investigated the distribution of sodium values within these groups and explored the relationship between serum sodium and death using logistic regression. RESULTS: Levels among hospital inpatients were significantly lower than in outpatients of the same age. Emergency admissions had lower levels and those admitted from care homes higher levels, risk of inhospital death began to rise at 140 mmol/L, well within the 'normal' range. Patients with a serum sodium concentration of 145 mmol/L on admission have a risk of inhospital death 3.7 times higher than that of a patient with a concentration of 140 mmol/L. CONCLUSIONS: The range for serum sodium concentration on admission in inpatients is broader and lower than the commonly accepted reference range. The risk of mortality increases at sodium concentration >139 mmol/L, well within reference range currently considered normal. PMID- 26561590 TI - Chemotherapy-induced nausea and vomiting: an overview and comparison of three consensus guidelines. AB - Chemotherapy-induced nausea and vomiting (CINV) remains one of the most debilitating toxicities associated with cancer treatment. In recent decades, significant strides have been made in our understanding of the pathophysiology of CINV, making way to more effective targeted pharmacotherapies, especially 5 hydroxytryptamine3 receptor antagonists and neurokinin-1 (NK-1) receptor antagonists. As much as 70%-80% of CINV can be prevented with appropriate administration of available antiemetics. Nevertheless, fear of CINV still may diminish cancer treatment adherence. To assimilate and summarise the rapidly growing body of clinical research literature on CINV, three professional organisations-the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology, the American Society of Clinical Oncology and the National Comprehensive Cancer Network-have created CINV management guidelines. While these respective guidelines are developed from similar consensus processes using similar clinical research literature, their results demonstrate several key differences in recommended strategies. This article aims to provide an overview of CINV pathophysiology, compare and contrast three expert guidelines and offer considerations for future clinical and research challenges. PMID- 26561591 TI - Distant site lipoatrophy: a rare complication of subcutaneous insulin therapy. PMID- 26561592 TI - Haemorrhoids: modern diagnosis and treatment. AB - Haemorrhoids present often to primary and secondary care, and haemorrhoidal procedures are among the most common carried out. They may co-exist with more serious pathology, and correct evaluation is important. In most cases a one-off colonoscopy in patients aged 50 or above with flexible sigmoidoscopy in younger patients is reasonable. Many people with haemorrhoids do not require treatment. Topical remedies provide no more than symptomatic relief-and even evidence for this is poor. Bulk laxatives alone may improve symptoms of both bleeding and prolapse and seem as effective as injection sclerotherapy. Rubber band ligation is effective in 75% of patients in the short term, but does not treat prolapsed haemorrhoids or those with a significant external component. Conventional haemorrhoidectomy remains the most effective treatment in the long term, the main limitation being post-operative pain. Metronidazole, topical sphincter relaxants and operative technique have all been shown to reduce pain. Stapled haemorrhoidectomy and haemorrhoidal artery ligation techniques are probably less effective but less painful. Long-term data are poor for all procedures, with many studies reporting only 1-3 years of follow-up data. Haemorrhoids are common in pregnancy, occurring in 40% of women. They can usually be treated conservatively during pregnancy, with any treatment delayed until after delivery. Acutely strangulated haemorrhoids may be treated either conservatively or operatively. There is an increased risk of anal stenosis after acute surgery, but the risks of sepsis and sphincter damage are less significant than previously thought. The majority of patients who are treated conservatively will still require definitive treatment at a later date. PMID- 26561593 TI - Cellular and molecular mechanisms of HGF/Met in the cardiovascular system. AB - Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFbeta1 (transforming growth factor beta1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the treatment of both coronary and peripheral artery disease. PMID- 26561594 TI - Vascular growth factors play critical roles in kidney glomeruli. AB - Kidney glomeruli ultrafilter blood to generate urine and they are dysfunctional in a variety of kidney diseases. There are two key vascular growth factor families implicated in glomerular biology and function, namely the vascular endothelial growth factors (VEGFs) and the angiopoietins (Angpt). We present examples showing not only how these molecules help generate and maintain healthy glomeruli but also how they drive disease when their expression is dysregulated. Finally, we review how manipulating VEGF and Angpt signalling may be used to treat glomerular disease. PMID- 26561595 TI - Spatial summation revealed in the earliest visual evoked component C1 and the effect of attention on its linearity. AB - In natural scenes, multiple objects are usually presented simultaneously. How do specific areas of the brain respond to multiple objects based on their responses to each individual object? Previous functional magnetic resonance imaging (fMRI) studies have shown that the activity induced by a multiobject stimulus in the primary visual cortex (V1) can be predicted by the linear or nonlinear sum of the activities induced by its component objects. However, there has been little evidence from electroencephelogram (EEG) studies so far. Here we explored how V1 responded to multiple objects by comparing the EEG signals evoked by a three grating stimulus with those evoked by its two components (the central grating and 2 flanking gratings). We focused on the earliest visual component C1 (onset latency of ~50 ms) because it has been shown to reflect the feedforward responses of neurons in V1. We found that when the stimulus was unattended, the amplitude of the C1 evoked by the three-grating stimulus roughly equaled the sum of the amplitudes of the C1s evoked by its two components, regardless of the distances between these gratings. When the stimulus was attended, this linear spatial summation existed only when the three gratings were far apart from each other. When the three gratings were close to each other, the spatial summation became compressed. These results suggest that the earliest visual responses in V1 follow a linear summation rule when attention is not involved and that attention can affect the earliest interactions between multiple objects. PMID- 26561596 TI - Estimation of the phase response curve from Parkinsonian tremor. AB - Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period. PMID- 26561598 TI - Intersegmental coordination elicited by unexpected multidirectional slipping-like perturbations resembles that adopted during steady locomotion. AB - This study aimed at testing the hypothesis that reactive biomechanical responses elicited by unexpected slipping-like perturbations delivered during steady walking are characterized by an intersegmental coordination strategy resembling that adopted during unperturbed walking. Fifteen healthy subjects were asked to manage multidirectional slipping-like perturbations delivered while they walked steadily. The planar covariation law of elevation angles related to lower limb segments was the main observed variable related to unperturbed and perturbed strides. Principal component analysis was used to verify whether elevation angles covaried, both before and after the onset of the perturbation, and, if so, the orientation of the related planes of covariation was compared. Results revealed that the planar covariation law of the unperturbed limb after onset of the perturbation was systematically similar to that seen during steady walking. This occurred despite differences in range of motion and intersubject variability of both elevation and joint angles. The analysis strongly corroborates the hypothesis that the planar covariation law emerges from the interaction between spinal neural networks and limb mechanical oscillators. In particular, fast and stereotyped reactive strategies may result from the interaction among activities of downstream neural networks encrypting well-trained motor schemes, such as those related to walking, limb dynamics, and sensory motor information gathered during the perturbation. In addition, our results allowed us to speculate that rehabilitative treatment based on unexpected perturbations and relying on the plasticity of the central nervous system may also be effective in eliciting unimpaired intralimb coordination in neurological patients. PMID- 26561597 TI - Two-stage muscle activity responses in decisions about leg movement adjustments during trip recovery. AB - Studies on neural decision making mostly investigated fast corrective adjustments of arm movements. However, fast leg movement corrections deserve attention as well, since they are often required to avoid falling after balance perturbations. The present study aimed at elucidating the mechanisms behind fast corrections of tripping responses by analyzing the concomitant leg muscle activity changes. This was investigated in seven young adults who were tripped in between normal walking trials and took a recovery step by elevating the tripped leg over the obstacle. In some trials, a forbidden landing zone (FZ) was presented behind the obstacle, at the subjects' preferred foot landing position, forcing a step correction. Muscle activity of the tripped leg gastrocnemius medialis (iGM), tibialis anterior (iTA), rectus femoris (iRF), and biceps femoris (iBF) muscles was compared between normal trips presented before any FZ appearance, trips with a FZ, and normal trips presented in between trips with a FZ ("catch" trials). When faced with a real or expected (catch trials) FZ, subjects shortened their recovery steps. The underlying changes in muscle activity consisted of two stages. The first stage involved reduced iGM activity, occurring at a latency shorter than voluntary reaction, followed by reduced iTA and increased iBF and iGM activities occurring at longer latencies. The fast response was not related to step shortening, but longer latency responses clearly were functional. We suggest that the initial response possibly acts as a "pause," allowing the nervous system to integrate the necessary information and prepare the subsequent, functional movement adjustment. PMID- 26561599 TI - Opposing aging-related shift of excitatory dopamine D1 and inhibitory D3 receptor protein expression in striatum and spinal cord. AB - Normal aging is associated with a decrease in motor function, a concomitant increase in muscle stiffness and tone, and a decrease in dopamine (DA) levels in the spinal cord. The striatum plays a critical role in the control of motor function, and it receives strong DA innervation from the substantia nigra. However, locomotor activity also requires the activation of motoneurons in the lumbar spinal cord, which in the mouse express all five DA receptor subtypes (D1 D5). Of these, the D3 receptor (D3R) expresses the highest affinity to DA and mediates inhibitory actions, while activation of the lower-affinity D1 receptor (D1R) system promotes excitatory effects. To test whether the aging-related decrease in DA levels is associated with corresponding changes in DA receptor protein expression levels, we probed with Western blot and immunohistochemical techniques for D1R and D3R protein expression levels over the normal life span of the mouse. We found that with age D1R expression levels increased in both striatum and spinal cord, while D3R expression levels remained stable in the striatum or slightly decreased in the spinal cord. The resulting D1-to-D3 ratio indicates a strong upregulation of D1R-mediated pathways in old animals, which is particularly pronounced in the lumbar spinal cord. These data suggest that aging may be associated with a shift in DA-mediated pathways in striatum and spinal cord, which in turn could be an underlying factor in the emergence of aging- and DA-related motor dysfunctions such as Parkinson's disease or Restless Legs Syndrome (RLS). PMID- 26561600 TI - High-frequency modulation of rat spinal field potentials: effects of slowly conducting muscle vs. skin afferents. AB - Long-term potentiation (LTP) in rat spinal dorsal horn neurons was induced by electrical high-frequency stimulation (HFS) of afferent C fibers. LTP is generally assumed to be a key mechanism of spinal sensitization. To determine the contribution of skin and muscle afferents to LTP induction, the sural nerve (SU, pure skin nerve) or the gastrocnemius-soleus nerve (GS, pure muscle nerve) were stimulated individually. As a measure of spinal LTP, C-fiber-induced synaptic field potentials (SFPs) evoked by the GS and by the SU were recorded in the dorsal horn. HFS induced a sustained increase of SFPs of the same nerve for at least 3 h, indicating the elicitation of homosynaptic nociceptive spinal LTP. LTP after muscle nerve stimulation (HFS to GS) was more pronounced (increase to 248%, P < 0.05) compared with LTP after skin nerve stimulation (HFS applied to SU; increase to 151% of baseline, P < 0.05). HFS applied to GS also increased the SFPs of the unconditioned SU (heterosynaptic LTP) significantly, whereas HFS applied to SU had no significant impact on the SFP evoked by the GS. Collectively, the data indicate that HFS of a muscle or skin nerve evoked nociceptive spinal LTP with large effect sizes for homosynaptic LTP (Cohen's d of 0.8-1.9) and small to medium effect sizes for heterosynaptic LTP (Cohen's d of 0.4-0.65). The finding that homosynaptic and heterosynaptic LTP after HFS of the muscle nerve were more pronounced than those after HFS of a skin nerve suggests that muscle pain may be associated with more extensive LTP than cutaneous pain. PMID- 26561601 TI - Basal forebrain dynamics during nonassociative and associative olfactory learning. AB - Cholinergic and GABAergic projections from the horizontal diagonal band (HDB) and medial preoptic area (MCPO) of the basal forebrain to the olfactory system are associated with odor discrimination and odor learning, as well as modulation of neural responses in olfactory structures. Whereas pharmacological and lesion studies give insights into the functional role of these modulatory inputs on a slow timescale, the response dynamics of neurons in the HDB/MCPO during olfactory behaviors have not been investigated. In this study we examined how these neurons respond during two olfactory behaviors: spontaneous investigation of odorants and odor-reward association learning. We observe rich heterogeneity in the response dynamics of individual HDB/MCPO neurons, with a substantial fraction of neurons exhibiting task-related modulation. HDB/MCPO neurons show both rapid and transient responses during bouts of odor investigation and slow, long-lasting modulation of overall response rate based on behavioral demands. Specifically, baseline rates were higher during the acquisition phase of an odor-reward association than during spontaneous investigation or the recall phase of an odor reward association. Our results suggest that modulatory projections from the HDB/MCPO are poised to influence olfactory processing on multiple timescales, from hundreds of milliseconds to minutes, and are therefore capable of rapidly setting olfactory network dynamics during odor processing and learning. PMID- 26561602 TI - Coherent and intermittent ensemble oscillations emerge from networks of irregular spiking neurons. AB - Local field potential (LFP) recordings from spatially distant cortical circuits reveal episodes of coherent gamma oscillations that are intermittent, and of variable peak frequency and duration. Concurrently, single neuron spiking remains largely irregular and of low rate. The underlying potential mechanisms of this emergent network activity have long been debated. Here we reproduce such intermittent ensemble oscillations in a model network, consisting of excitatory and inhibitory model neurons with the characteristics of regular-spiking (RS) pyramidal neurons, and fast-spiking (FS) and low-threshold spiking (LTS) interneurons. We find that fluctuations in the external inputs trigger reciprocally connected and irregularly spiking RS and FS neurons in episodes of ensemble oscillations, which are terminated by the recruitment of the LTS population with concurrent accumulation of inhibitory conductance in both RS and FS neurons. The model qualitatively reproduces experimentally observed phase drift, oscillation episode duration distributions, variation in the peak frequency, and the concurrent irregular single-neuron spiking at low rate. Furthermore, consistent with previous experimental studies using optogenetic manipulation, periodic activation of FS, but not RS, model neurons causes enhancement of gamma oscillations. In addition, increasing the coupling between two model networks from low to high reveals a transition from independent intermittent oscillations to coherent intermittent oscillations. In conclusion, the model network suggests biologically plausible mechanisms for the generation of episodes of coherent intermittent ensemble oscillations with irregular spiking neurons in cortical circuits. PMID- 26561603 TI - Properties of pattern and component direction-selective cells in area MT of the macaque. AB - Neurons in area MT/V5 of the macaque visual cortex encode visual motion. Some cells are selective for the motion of oriented features (component direction selective, CDS); others respond to the true direction of complex patterns (pattern-direction selective, PDS). There is a continuum of selectivity in MT, with CDS cells at one extreme and PDS cells at the other; we compute a pattern index that captures this variation. It is unknown how a neuron's pattern index is related to its other tuning characteristics. We therefore analyzed the responses of 792 MT cells recorded in the course of other experiments from opiate anesthetized macaque monkeys, as a function of the direction, spatial frequency, drift rate, size, and contrast of sinusoidal gratings and of the direction and speed of random-dot textures. We also compared MT responses to those of 718 V1 cells. As expected, MT cells with higher pattern index tended to have stronger direction selectivity and broader direction tuning to gratings, and they responded better to plaids than to gratings. Strongly PDS cells also tended to have smaller receptive fields and stronger surround suppression. Interestingly, they also responded preferentially to higher drift rates and higher speeds of moving dots. The spatial frequency preferences of PDS cells depended strongly on their preferred temporal frequencies, whereas these preferences were independent in component-selective cells. Pattern direction selectivity is statistically associated with many response properties of MT cells but not strongly associated with any particular property. Pattern-selective signals are thus available in association with most other signals exported by MT. PMID- 26561604 TI - Slow maturation of planning in obstacle avoidance in humans. AB - Complex gait (e.g., obstacle avoidance) requires a higher cognitive load than simple steady-state gait, which is a more automated movement. The higher levels of the central nervous system, responsible for adjusting motor plans to complex gait, develop throughout childhood into adulthood. Therefore, we hypothesize that gait strategies in complex gait are likely to mature until adulthood as well. However, little is known about the maturation of complex gait from childhood into adolescence and adulthood. To address this issue, we investigated obstacle avoidance in forty-four 8- to 18-yr-old participants who walked at preferred speed along a 6-m walkway on which a planar obstacle (150% of step length, 1 m wide) was projected. Participants avoided the obstacle by stepping over this projection, while lower body kinematics were recorded. Results showed that step length and speed adjustments during successful obstacle avoidance were similar across all ages, even though younger children modified step width to a greater extent. Additionally, the younger children used larger maximal toe elevations and take-off distances than older children. Moreover, during unsuccessful trials, younger children deployed exaggerated take-off distances, which resulted in obstacle contact upon the consecutive heel strike. These results indicate that obstacle avoidance is not fully matured in younger children, and that the inability to plan precise foot placements is an important factor contributing to failures in obstacle avoidance. PMID- 26561605 TI - Primary motor cortex LTP/LTD-like plasticity in probable corticobasal syndrome. AB - Whether the primary motor cortex (M1) contributes to the pathophysiology of corticobasal syndrome (CBS) remains unclear. In this study in patients with probable CBS, we tested whether M1 plasticity contributes to the pathophysiology of symptoms in the contralateral "less affected" limb, manifesting only parkinsonism, and in the contralateral "more affected" limb, manifesting parkinsonism plus other motor and nonmotor symptoms. In Experiment 1, we applied intermittent/continuous theta-burst stimulation (iTBS/cTBS) over the M1 contralateral to the less affected limb in 17 patients. In Experiment 2, we applied iTBS/cTBS over the M1 contralateral to the more affected limb in 14 of the 17 patients. We measured iTBS/cTBS-induced plasticity as reflected by motor evoked potential (MEP) changes. Data were compared with those obtained in 17 healthy subjects (HS). In Experiment 1, TBS over the M1 contralateral to the less affected limb disclosed reduced plasticity in patients than in HS. In Experiment 2, in 5 of 14 patients we recorded abnormally low-amplitude MEPs, preventing the evaluation of plasticity in the M1 contralateral to the more affected limb. In the remaining nine patients, TBS disclosed abnormal plasticity characterized by high intersubject variability. In these nine patients, the response to TBS correlated with specific patients' clinical features. In the present study in patients with probable CBS, we have demonstrated heterogeneous abnormalities of M1 that contribute to the pathophysiology of this condition. PMID- 26561606 TI - CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia. AB - Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo] pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane. PMID- 26561607 TI - Balanced ionotropic receptor dynamics support signal estimation via voltage dependent membrane noise. AB - Encoding behaviorally relevant stimuli in a noisy background is critical for animals to survive in their natural environment. We identify core biophysical and synaptic mechanisms that permit the encoding of low-frequency signals in pyramidal neurons of the weakly electric fish Apteronotus leptorhynchus, an animal that can accurately encode even miniscule amplitude modulations of its self-generated electric field. We demonstrate that slow NMDA receptor (NMDA-R) mediated excitatory postsynaptic potentials (EPSPs) are able to summate over many interspike intervals (ISIs) of the primary electrosensory afferents (EAs), effectively eliminating the baseline EA ISI correlations from the pyramidal cell input. Together with a dynamic balance of NMDA-R and GABA-A-R currents, this permits stimulus-evoked changes in EA spiking to be transmitted efficiently to target electrosensory lobe (ELL) pyramidal cells, for encoding low-frequency signals. Interestingly, AMPA-R activity is depressed and appears to play a negligible role in the generation of action potentials. Instead, we hypothesize that cell-intrinsic voltage-dependent membrane noise supports the encoding of perithreshold sensory input; this noise drives a significant proportion of pyramidal cell spikes. Together, these mechanisms may be sufficient for the ELL to encode signals near the threshold of behavioral detection. PMID- 26561608 TI - Single-trial decoding of intended eye movement goals from lateral prefrontal cortex neural ensembles. AB - Neurons in the lateral prefrontal cortex (LPFC) encode sensory and cognitive signals, as well as commands for goal-directed actions. Therefore, the LPFC might be a good signal source for a goal-selection brain-computer interface (BCI) that decodes the intended goal of a motor action previous to its execution. As a first step in the development of a goal-selection BCI, we set out to determine if we could decode simple behavioral intentions to direct gaze to eight different locations in space from single-trial LPFC neural activity. We recorded neuronal spiking activity from microelectrode arrays implanted in area 8A of the LPFC of two adult macaques while they made visually guided saccades to one of eight targets in a center-out task. Neuronal activity encoded target location immediately after target presentation, during a delay epoch, during the execution of the saccade, and every combination thereof. Many (40%) of the neurons that encoded target location during multiple epochs preferred different locations during different epochs. Despite heterogeneous and dynamic responses, the neuronal feature set that best predicted target location was the averaged firing rates from the entire trial and it was best classified using linear discriminant analysis (63.6-96.9% in 12 sessions, mean 80.3%; information transfer rate: 21 59, mean 32.8 bits/min). Our results demonstrate that it is possible to decode intended saccade target location from single-trial LPFC activity and suggest that the LPFC is a suitable signal source for a goal-selection cognitive BCI. PMID- 26561609 TI - Chronic imaging of movement-related Purkinje cell calcium activity in awake behaving mice. AB - Purkinje cells (PCs) are a major site of information integration and plasticity in the cerebellum, a brain region involved in motor task refinement. Thus PCs provide an ideal location for studying the mechanisms necessary for cerebellum dependent motor learning. Increasingly, sophisticated behavior tasks, used in combination with genetic reporters and effectors of activity, have opened up the possibility of studying cerebellar circuits during voluntary movement at an unprecedented level of quantitation. However, current methods used to monitor PC activity do not take full advantage of these advances. For example, single-unit or multiunit electrode recordings, which provide excellent temporal information regarding electrical activity, only monitor a small population of cells and can be quite invasive. Bolus loading of cell-permeant calcium (Ca(2+)) indicators is short-lived, requiring same-day imaging immediately after surgery and/or indicator injection. Genetically encoded Ca(2+) indicators (GECIs) overcome many of these limits and have garnered considerable use in many neuron types but only limited use in PCs. Here we employed these indicators to monitor Ca(2+) activity in PCs over several weeks. We could repeatedly image from the same cerebellar regions across multiple days and observed stable activity. We used chronic imaging to monitor PC activity in crus II, an area previously linked to licking behavior, and identified a region of increased activity at the onset of licking. We then monitored this same region after training tasks to initiate voluntary licking behavior in response to different sensory stimuli. In all cases, PC Ca(2+) activity increased at the onset of rhythmic licking. PMID- 26561611 TI - Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials. AB - Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to -20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na(+) current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na(+)-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to "touch up" but not to generate APs. PMID- 26561610 TI - Functional NMDA receptors are expressed by both AII and A17 amacrine cells in the rod pathway of the mammalian retina. AB - At many glutamatergic synapses, non-N-methyl-d-aspartate (NMDA) and NMDA receptors are coexpressed postsynaptically. In the mammalian retina, glutamatergic rod bipolar cells are presynaptic to two rod amacrine cells (AII and A17) that constitute dyad postsynaptic partners opposite each presynaptic active zone. Whereas there is strong evidence for expression of non-NMDA receptors by both AII and A17 amacrines, the expression of NMDA receptors by the pre- and postsynaptic neurons in this microcircuit has not been resolved. In this study, using patch-clamp recording from visually identified cells in rat retinal slices, we investigated the expression and functional properties of NMDA receptors in these cells with a combination of pharmacological and biophysical methods. Pressure application of NMDA did not evoke a response in rod bipolar cells, but for both AII and A17 amacrines, NMDA evoked responses that were blocked by a competitive antagonist (CPP) applied extracellularly and an open channel blocker (MK-801) applied intracellularly. NMDA-evoked responses also displayed strong Mg(2+)-dependent voltage block and were independent of gap junction coupling. With low-frequency application (60-s intervals), NMDA-evoked responses remained stable for up to 50 min, but with higher-frequency stimulation (10- to 20-s intervals), NMDA responses were strongly and reversibly suppressed. We observed strong potentiation when NMDA was applied in nominally Ca(2+)-free extracellular solution, potentially reflecting Ca(2+)-dependent NMDA receptor inactivation. These results indicate that expression of functional (i.e., conductance-increasing) NMDA receptors is common to both AII and A17 amacrine cells and suggest that these receptors could play an important role for synaptic signaling, integration, or plasticity in the rod pathway. PMID- 26561612 TI - Circulating Tumor Cells, a Tremendous Prognostic Factor in Inflammatory Breast Cancer. PMID- 26561613 TI - Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial. AB - BACKGROUND: Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction. OBJECTIVE: We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function. DESIGN: We conducted a double-blind, randomized, placebo controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre-randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio]. RESULTS: We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: -0.03, -0.00; P = 0.040) in women taking UNIMMAP. CONCLUSIONS: Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662. PMID- 26561614 TI - Short-term effects of a hypocaloric diet with low glycemic index and low glycemic load on body adiposity, metabolic variables, ghrelin, leptin, and pregnancy rate in overweight and obese infertile women: a randomized controlled trial. AB - BACKGROUND: Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity. OBJECTIVE: We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF). DESIGN: The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined. RESULTS: There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P < 0.05). Despite a change of 18% in mean values, there was no significant increase in acylated ghrelin concentrations in the LGI group compared with the control group (P = 0.215). The LGI-diet group had 85.4% more oocytes retrieved than did the control group (7.75 +/- 1.44 and 4.18 +/- 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births. CONCLUSIONS: The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960. PMID- 26561615 TI - Comparative effects of intraduodenal whey protein hydrolysate on antropyloroduodenal motility, gut hormones, glycemia, appetite, and energy intake in lean and obese men. AB - BACKGROUND: In lean individuals, intraduodenal protein and lipid modulate gastrointestinal motor and hormone functions and reduce energy intake in a load dependent manner; protein also stimulates insulin, with modest effects on reducing blood glucose. The effect of intraduodenal lipid on gastrointestinal motor and hormone responses is diminished in obesity; whether the effects of protein are also attenuated remains unclear. OBJECTIVES: The objectives of this study were to characterize the load-dependent effects of intraduodenal whey protein hydrolysate on antropyloroduodenal pressures, gut hormones, glycemia, appetite, and energy intake in obese subjects and to compare the responses to the higher protein load with those in lean subjects. DESIGN: We measured antropyloroduodenal pressures, plasma cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, blood glucose, appetite, and energy intake in 12 nondiabetic obese men on 3 separate occasions, in a double-blind, randomized order, during 60-min intraduodenal infusions of hydrolyzed whey protein at either 0 (saline control), 1.5, or 3 kcal/min. Twelve age-matched lean individuals received a 3-kcal/min infusion only. Immediately after the infusions, energy intake from a buffet lunch was quantified. RESULTS: In obese subjects, protein suppressed antral and duodenal pressures; stimulated plasma CCK, GLP-1, GIP, insulin, and glucagon (all r > 0.57, P < 0.01); and tended to reduce energy intake (r = -10.38, P = 0.057) in a dose-dependent manner. In response to the 3-kcal/min protein load, antropyloroduodenal pressures, CCK, GLP-1, and glucagon did not differ between lean and obese subjects. Insulin release was greater, and GIP release less, in obese than in lean subjects (both P < 0.05), whereas the reduction in glucose was comparable. Energy intake tended to be higher in obese subjects (P = 0.08). CONCLUSIONS: The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin-incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853. PMID- 26561616 TI - Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. AB - BACKGROUND: The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established. OBJECTIVES: We examined the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids [total cholesterol, low density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides], lipoproteins [apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100], blood pressure, and inflammation (C-reactive protein) in adults aged >=18 y without prevalent CVD. DESIGN: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta regression. Publication bias was evaluated by using funnel plots and Egger's and Begg's tests. RESULTS: Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (-4.7 mg/dL; 95% CI: -5.3, -4.0 mg/dL), LDL cholesterol (-4.8 mg/dL; 95% CI: -5.5, -4.2 mg/dL), ApoB (-3.7 mg/dL; 95% CI: -5.2, -2.3 mg/dL), and triglycerides (-2.2 mg/dL; 95% CI: -3.8, -0.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity < 0.001 each); stronger effects were observed for >=60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (-11.5 mg/dL; 95% CI: 16.2, -6.8 mg/dL) than in healthy populations (-2.5 mg/dL; 95% CI: -4.7, -0.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found. CONCLUSIONS: Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations. PMID- 26561618 TI - Are strict vegetarians protected against prostate cancer? AB - BACKGROUND: According to the American Cancer Society, prostate cancer accounts for ~27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. OBJECTIVE: This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. DESIGN: In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. RESULTS: In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). CONCLUSION: Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null. PMID- 26561619 TI - Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial. AB - BACKGROUND: During fetal and perinatal periods, many nutrients, such as long chain polyunsaturated fatty acids [contained in fish oil (FO)] and folate, are important in achieving normal brain development. Several studies have shown the benefits of early nutrition on children's neurocognitive development. However, the evidence with regard to the attention system is scarce. OBJECTIVES: The aim of this study was to analyze the long-term effects of FO, 5 methyltetrahydrofolate (5-MTHF), or FO+5-MTHF prenatal supplementation on attention networks. DESIGN: Participants were 136 children born to mothers from the NUHEAL (Nutraceuticals for a Healthy Life) project (randomly assigned to receive FO and/or 5-MTHF or placebo prenatal supplementation) who were recalled for a new examination 8.5 y later. The response conflict-resolution ability (using congruent and incongruent conditions)), alerting, and spatial orienting of attention were evaluated with behavioral measures (Attention Network Test), electroencephalography/event-related potentials (ERPs), and standardized low resolution brain electromagnetic tomography (sLORETA). RESULTS: Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups (all P < 0.05). Differences between ERP amplitudes for the conflict conditions were also observed. sLORETA analysis showed higher activation of the right midcingulate cortex for the incongruent condition. In addition, a significant slowing down of response speed depending on the warning cue in the 5-MTHF and FO groups was observed. CONCLUSIONS: Folate supplementation during pregnancy, rather than FO or FO+5-MTHF supplementation, improves children's ability to solve response conflicts. This advantage seems to be based on the higher activation of the midcingulate cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions. This trial was registered at clinicaltrials.gov as NCT01180933. PMID- 26561620 TI - Low levels of physical activity are associated with dysregulation of energy intake and fat mass gain over 1 year. AB - BACKGROUND: Previous studies suggest that appetite may be dysregulated at low levels of activity, creating an energy imbalance that results in weight gain. OBJECTIVE: The aim was to examine the relation between energy intake, physical activity, appetite, and weight gain during a 1-y follow-up period in a large sample of adults. DESIGN: Participants included 421 individuals (mean +/- SD age: 27.6 +/- 3.8 y). Measurements included the following: energy intake with the use of interviewer-administered dietary recalls and calculated by using changes in body composition and energy expenditure, moderate-to-vigorous physical activity (MVPA) with the use of an arm-based monitor, body composition with the use of dual-energy X-ray absorptiometry, and questionnaire-derived perceptions of dietary restraint, disinhibition, hunger, and control of eating. Participants were grouped at baseline into quintiles of MVPA (min/d) by sex. Measurements were repeated every 3 mo for 1 y. RESULTS: At baseline, an inverse relation existed between body weight and activity groups, with the least-active group (15.7 +/- 9.9 min MVPA/d, 6062 +/- 1778 steps/d) having the highest body weight (86.3 +/- 13.2 kg) and the most-active group (174.5 +/- 60.5 min MVPA/d, 10260 +/- 3087 steps/d) having the lowest body weight (67.5 +/- 11.0 kg). A positive relation was observed between calculated energy intake and activity group, except in the lowest quintile of activity. The lowest physical activity group reported higher levels of disinhibition (P = 0.07) and cravings for savory foods (P = 0.03) compared with the group with the highest level of physical activity. Over 1 y of follow-up, the lowest activity group gained the largest amount of fat mass (1.7 +/- 0.3 kg) after adjustment for change in MVPA and baseline fat mass. The odds of gaining >3% of fat mass were between 1.8 and 3.8 times as high for individuals in the least-active group as for those in the middle activity group. CONCLUSIONS: These results suggest that low levels of physical activity are a risk factor for fat mass gain. In the current sample, a threshold for achieving energy balance occurred at an activity level corresponding to 7116 steps/d, an amount achievable by most adults. This trial was registered at clinicaltrials.gov as NCT01746186. PMID- 26561621 TI - Intake of carbohydrates during pregnancy in obese women is associated with fat mass in the newborn offspring. AB - BACKGROUND: Transmission of obesity across generations is of concern. Offspring of obese women have short- and long-term increased morbidities. A high intake of carbohydrate during pregnancy combined with impaired glucose tolerance is postulated to result in high birth weight, which is linked to subsequent metabolic disease. OBJECTIVE: The objective was to examine the association between carbohydrate intake in obese pregnant women and their offspring's body composition. DESIGN: Secondary analyses were performed in an observational setting of 222 pregnant women with a pregestational BMI (in kg/m(2)) >=30 participating in a randomized controlled trial. Diet was assessed at gestational weeks 11-14 and 36-37 by using a semiquantitative food-frequency questionnaire. Body composition in the offspring was assessed at birth by dual-energy X-ray absorptiometry. Relative fat mass (%) was the primary outcome. Absolute measures (total fat, abdominal fat, and lean body mass) were secondary outcomes. RESULTS: Mean +/- SD weight and absolute and relative fat mass in the offspring at birth were 3769 +/- 542 g, 436 +/- 214 g, and 11% +/- 4%, respectively. Maternal intake of digestible carbohydrates was associated with the offspring's relative fat mass in late (P-trend = 0.006) but not early (P-trend = 0.15) pregnancy. A comparison of mothers in the highest (median: 238 g/d) compared with the lowest (median: 188 g/d) quartile of digestible carbohydrate intake showed a mean adjusted higher value in the offspring's relative fat mass of 2.1% (95% CI: 0.6%, 3.7%), which corresponded in absolute terms to a 103-g (95% CI: 27, 179-g) higher fat mass. Abdominal fat mass was also higher. In a strata of women with well-controlled glucose (2-h glucose values <=6.6 mmol/L), no association between carbohydrate intake and offspring fat mass was observed, but the associations became significant and increased in strength with higher intolerance (strata with 2-h glucose values between 6.7-7.7 and >=7.8 mmol/L). CONCLUSION: In obese women, even those without gestational diabetes but with impaired glucose tolerance, a lower carbohydrate intake at moderate levels in late gestation is associated with a lower fat mass in their offspring at birth. The TOP study was registered at clinicaltrials.gov as NCT01345149. PMID- 26561617 TI - Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease. AB - BACKGROUND: Dietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake. OBJECTIVE: The aim was to evaluate the association between total fat intake and fat subtypes with the risk of CVD (myocardial infarction, stroke, or death from cardiovascular causes) and cardiovascular and all-cause death. We also examined the hypothetical effect of the isocaloric substitution of one macronutrient for another. DESIGN: We prospectively studied 7038 participants at high CVD risk from the PREvencion con DIeta MEDiterranea (PREDIMED) study. The trial was conducted from 2003 to 2010, but the present analysis was based on an expanded follow-up until 2012. At baseline and yearly thereafter, total and specific fat subtypes were repeatedly measured by using validated food-frequency questionnaires. Time dependent Cox proportional hazards models were used. RESULTS: After 6 y of follow up, we documented 336 CVD cases and 414 total deaths. HRs (95% CIs) for CVD for those in the highest quintile of total fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake compared with those in the lowest quintile were 0.58 (0.39, 0.86), 0.50 (0.31, 0.81), and 0.68 (0.48, 0.96), respectively. In the comparison between extreme quintiles, higher saturated fatty acid (SFA) and trans-fat intakes were associated with 81% (HR: 1.81; 95% CI: 1.05, 3.13) and 67% (HR: 1.67; 95% CI: 1.09, 2.57) higher risk of CVD. Inverse associations with all-cause death were also observed for PUFA and MUFA intakes. Isocaloric replacements of SFAs with MUFAs and PUFAs or trans fat with MUFAs were associated with a lower risk of CVD. SFAs from pastries and processed foods were associated with a higher risk of CVD. CONCLUSIONS: Intakes of MUFAs and PUFAs were associated with a lower risk of CVD and death, whereas SFA and trans-fat intakes were associated with a higher risk of CVD. The replacement of SFAs with MUFAs and PUFAs or of trans fat with MUFAs was inversely associated with CVD. This trial was registered at www.controlled-trials.com as ISRCTN 35739639. PMID- 26561622 TI - In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight women. AB - BACKGROUND: Iron deficiency is common in overweight and obese individuals. This deficiency may be due to adiposity-related inflammation that increases serum hepcidin and decreases dietary iron absorption. Because hepcidin reduces iron efflux from the basolateral enterocyte, it is uncertain whether luminal enhancers of dietary iron absorption such as ascorbic acid can be effective in overweight and obese individuals. OBJECTIVE: In this study, we compared iron absorption from a meal with ascorbic acid (+AA) and a meal without ascorbic acid (-AA) in women in a normal-weight group (NW) with those in overweight and obese groups combined (OW/OB). DESIGN: Healthy, nonanemic women [n = 62; BMI (in kg/m(2)): 18.5-39.9] consumed a stable-isotope-labeled wheat-based test meal -AA and a wheat-based test meal +AA (31.4 mg ascorbic acid). We measured iron absorption and body composition with the use of dual-energy X-ray absorptiometry, blood volume with the use of a carbon monoxide (CO)-rebreathing method, iron status, inflammation, and serum hepcidin. RESULTS: Inflammatory biomarkers (all P < 0.05) and hepcidin (P = 0.08) were lower in the NW than in the OW/OB. Geometric mean (95% CI) iron absorptions in the NW and OW/OB were 19.0% (15.2%, 23.5%) and 12.9% (9.7%, 16.9%) (P = 0.049), respectively, from -AA meals and 29.5% (23.3%, 38.2%) and 16.6% (12.8%, 21.7%) (P = 0.004), respectively, from +AA meals. Median percentage increases in iron absorption for -AA to +AA meals were 56% in the NW (P < 0.001) and 28% in OW/OB (P = 0.006). Serum ferritin [R(2) = 0.22; beta = -0.17 (95% CI: 0.25, -0.09)], transferrin receptor [R(2) = 0.23; beta = 2.79 (95% CI: 1.47, 4.11)], and hepcidin [R(2) = 0.13; beta = -0.85 (95% CI: -1.41, -0.28)] were significant predictors of iron absorption. CONCLUSIONS: In overweight and obese women, iron absorption is two-thirds that in normal-weight women, and the enhancing effect of ascorbic acid on iron absorption is one-half of that in normal-weight women. Recommending higher intakes of ascorbic acid (or other luminal enhancers of iron absorption) in obese individuals to improve iron status may have a limited effect. This trial was registered at clinicaltrials.gov as NCT01884506. PMID- 26561623 TI - Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin. AB - BACKGROUND: The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (omega-3) fatty acids. OBJECTIVE: We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin. DESIGN: MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1. RESULTS: Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group. CONCLUSIONS: Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability to mount an appropriate response to infection. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000708055. PMID- 26561624 TI - Prebiotic consumption and the incidence of overweight in a Mediterranean cohort: the Seguimiento Universidad de Navarra Project. AB - BACKGROUND: The consumption of prebiotics (fermentable and nondigestible carbohydrates) has been proposed as a potentially protective factor against overweight and obesity. However, to our knowledge, no previous prospective studies have assessed the association between the consumption of prebiotics and the incidence of overweight or obesity. OBJECTIVE: We evaluated the association between prebiotic consumption [fructans and galacto-oligosaccharides (GOSs)] and the incidence of overweight [body mass index (BMI; in kg/m(2)) >=25] in the SUN (Seguimiento Universidad de Navarra) Project, which is a prospective cohort of Spanish, middle-aged university graduates with initial BMI <25. DESIGN: The SUN Project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with an overall retention rate of 90%. The study population encompassed 8569 Spanish university graduates (mean age: 37 y) who were initially free of overweight or obesity. Self-reported weight (previously validated) was collected at baseline and updated every 2 y during the follow-up period. Fructan consumption and GOS consumption were assessed with the use of a validated semiquantitative 136-item food-frequency questionnaire and were updated after 10 y. Time-dependent Cox proportional hazards models were used to estimate HRs and 95% CIs for incident overweight and to adjust for potential confounding factors. RESULTS: During follow-up (median: 9 y), 1964 incident cases of overweight were identified. After potential confounders were adjusted for, risk of overweight was 15% lower in participants in the highest quartile of fructan consumption (>=2.3 g/d) (95% CI: 0.74, 0.97; P-trend = 0.019). Subjects in the highest quartile of GOS consumption (>=0.45 g/d) had 17% lower risk of overweight (95% CI: 0.74, 0.94; P-trend = 0.001). CONCLUSIONS: Higher prebiotic consumption was associated with lower risk of overweight in a cohort of initially normal-weight, middle-aged adults. This potential protection has been previously scarcely assessed; therefore, additional longitudinal studies are needed to confirm our results. PMID- 26561625 TI - Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus. AB - BACKGROUND: A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. OBJECTIVE: We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fiber supplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM. DESIGN: A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter & Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients. RESULTS: We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97% (-10.6 mmol/mol); P = 0.048]. Glycemic effects were proportional to baseline FBG; no significant glucose lowering was observed in euglycemic subjects, a modest improvement was observed in subjects with pre-T2DM, and the greatest improvement was observed in subjects who were being treated for T2DM. CONCLUSIONS: These data indicate that psyllium would be an effective addition to a lifestyle-intervention program. The degree of psyllium's glycemic benefit was commensurate with the loss of glycemic control. Because the greatest effect was seen in patients who were being treated for T2DM, additional studies are needed to determine how best to incorporate psyllium into existing prevention and treatment algorithms with concomitant hypoglycemic medications. PMID- 26561626 TI - Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. AB - BACKGROUND: Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications. OBJECTIVE: We reviewed all available guidelines on the management of ID worldwide. DESIGN: A literature search was conducted in PubMed, Cochrane, and EMBASE and in main professional association websites, limited to documents published between 1 January 2004 and 30 June 2014. RESULTS: Of 127 guidelines identified, 29 were selected, involving 29 professional associations and issued from the United States (n = 8), Europe (n = 6), Britain (n = 4), Canada (n = 3), international organizations (n = 2), France (n = 2), Poland (n = 1), Australia (n = 1), Mexico (n = 1), and Japan (n = 1). A total of 22 and 27 guidelines provided recommendations on diagnosis and treatment of ID, respectively. To define ID, all guidelines recommended a concentration for serum ferritin. One-half of them (10 of 22) proposed transferrin saturation (TSAT) as an alternative or complementary diagnostic test. To treat ID, most of the guidelines (18 of 27) recommended preferentially the oral route if possible, particularly in children and in women in the pre- or postpregnancy period. Iron supplementation should be administered intravenously according to 13 of 27 guidelines, particularly in patients with chronic kidney disease (CKD) (n = 7) and chemotherapy-induced anemia (n = 5). Treatment targets for ID included an increase in hemoglobin concentrations to 10-12 g/dL or normalization (n = 8) and serum ferritin >100 MUg/L (n = 7) or 200 MUg/L (n = 4). For the latter, in some situations, such as CKD, ferritin concentrations should not exceed 500 MUg/L (n = 5) or 800 MUg/L (n = 5). Only 9 guidelines recommended TSAT as a target, proposing various thresholds ranging from 20% to 50%. CONCLUSIONS: It appears that for the diagnosis of ID, a cutoff of 100 MUg/L for serum ferritin concentration should be considered in most conditions and 20% for TSAT, except in particular situations, including young healthy women with heavy menstrual flow. New indications of intravenous iron supplementation are emerging. PMID- 26561627 TI - Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. AB - BACKGROUND: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation. OBJECTIVE: This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure. DESIGN: Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received >75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Whole-blood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures. RESULTS: Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations >30 MUg/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 MUg/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R. CONCLUSION: A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730. PMID- 26561628 TI - Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study. AB - BACKGROUND: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195. PMID- 26561630 TI - Exercise and energy balance: going to extremes to show that body weight is not the best outcome. PMID- 26561629 TI - Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults. AB - BACKGROUND: Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. OBJECTIVE: With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. DESIGN: Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7 compartment model. RESULTS: Subjects absorbed a mean +/- SEM of 23% +/- 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 +/- 0.3 and 8.8 +/- 0.6 d, respectively; P < 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 +/- 7 and 48 +/- 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis lycopene isomerization was predictive of plasma (13)C and unlabeled cis- and all trans-lycopene concentrations. Although the bioavailability of cis (24.5% +/- 6%) and all-trans (23.2% +/- 8%) isomers did not differ, endogenous isomerization (0.97 +/- 0.25 MUmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. CONCLUSION: (13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340. PMID- 26561632 TI - Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial. AB - BACKGROUND: Adverse effects of industrially produced trans fatty acids (iTFAs) on the risk of coronary artery disease are well documented in the scientific literature; however, effects of naturally occurring trans fatty acids (TFAs) from ruminant animals (rTFA), such as vaccenic acid (VA) and cis-9,trans-11 conjugated linoleic acid (c9,t11-CLA), are less clear. Although animal and cell studies suggest that VA and c9,t11-CLA may be hypocholesterolemic and antiatherogenic, epidemiologic data comparing rTFAs and iTFAs are inconsistent, and human intervention studies have been limited, underpowered, and not well controlled. OBJECTIVE: We determined the effects of VA, c9,t11-CLA, and iTFA, in the context of highly controlled diets (24 d each), on lipoprotein risk factors compared with a control diet. RESULTS: We conducted a double-blind, randomized, crossover feeding trial in 106 healthy adults [mean +/- SD age: 47 +/- 10.8 y; body mass index (in kg/m(2)): 28.5 +/- 4.0; low-density lipoprotein (LDL) cholesterol: 3.24 +/- 0.63 mmol/L]. Diets were designed to have stearic acid replaced with the following TFA isomers (percentage of energy): 0.1% mixed isomers of TFA (control), ~3% VA, ~3% iTFA, or 1% c9,t11-CLA. Total dietary fat (34% of energy) and other macronutrients were matched. Total cholesterol (TC), LDL cholesterol, triacylglycerol, lipoprotein(a), and apolipoprotein B were higher after VA than after iTFA; high-density lipoprotein (HDL) cholesterol and apolipoprotein AI also were higher after VA. Compared with control, VA and iTFA both increased TC, LDL cholesterol, ratio of TC to HDL cholesterol, and apolipoprotein B (2-6% change; P < 0.05); VA also increased HDL cholesterol, apolipoprotein AI, apolipoprotein B, and lipoprotein(a) (2-6% change; P < 0.05), whereas iTFA did not. c9,t11-CLA lowered triacylglycerol (P <= 0.01) and had no effect on other lipoprotein risk factors. CONCLUSIONS: With respect to risk of cardiovascular disease, these results are consistent with current nutrition labeling guidelines, with the requirement of VA, but not c9,t11-CLA, to be listed under TFA on the Nutrition Facts Panel. This trial was registered at clinicaltrials.gov as NCT00942656. PMID- 26561631 TI - The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition. AB - BACKGROUND: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. RESULTS: The multivariable-adjusted RR of having >=4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. CONCLUSION: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury. PMID- 26561633 TI - In equal amounts, the major ruminant trans fatty acid is as bad for LDL cholesterol as industrially produced trans fatty acids, but the latter are easier to remove from foods. PMID- 26561636 TI - Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV). AB - BACKGROUND: Exposure to fine particulate matter (PM2.5) may promote hepatic tumorgenesis through low-grade inflammation. Therefore, we assessed the association of long-term exposure levels of PM2.5 and subsequent risk of hepatocellular carcinoma (HCC) and investigated the mediation effect of inflammation as represented by alanine aminotransferase (ALT) on this association. METHODS: Between 1991 and 1992, we recruited 23 820 participants in Taiwan with no history of HCC. Case patients of HCC were ascertained through computerized data linkage with the National Cancer Registry and death certification systems. Participants' exposures to PM2.5 were based on a four-year average retrieved from stationary monitoring sites. Cox proportional hazards models were used to assess the association between PM2.5 exposure and HCC incidence. Mediation effects of ALT on PM2.5-associated HCC incidence were estimated. RESULTS: A total of 464 HCC cases were newly diagnosed with a median follow-up of 16.9 years. Statistically significantly increasing trends between PM2.5 exposures and ALT were observed on the Main Island and Penghu Islets. The adjusted hazard ratio (HR) for HCC on the Penghu Islets was 1.22 (95% confidence interval [CI] = 1.02 to 1.47) per PM2.5 interquartile range (IQR) increment (0.73 ug/m(3)) exposure. We also found a positive association between PM2.5 exposure (per IQR increment, 13.1 ug/m(3)) and HCC incidence on the Main Island. Furthermore, ALT had a statistically significant mediation effect on PM2.5 associated HCC incidence (HR = 1.17, 95% CI = 1.02 to1.52 on the Main Island; HR = 1.04, 95% CI = 1.03 to 1.07 on the Penghu Islets) per PM2.5 IQR increment. CONCLUSIONS: Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis. PMID- 26561637 TI - PKA and phosphatases attached to the Ca(V)1.2 channel regulate channel activity in cell-free patches. AB - Calmodulin (CaM) + ATP can reprime voltage-gated L-type Ca(2+) channels (Ca(V)1.2) in inside-out patches for activation, but this effect decreases time dependently. This suggests that the Ca(V)1.2 channel activity is regulated by additional cytoplasmic factors. To test this hypothesis, we examined the role of cAMP-dependent protein kinase A (PKA) and protein phosphatases in the regulation of Ca(V)1.2 channel activity in the inside-out mode in guinea pig ventricular myocytes. Ca(V)1.2 channel activity quickly disappeared after the patch was excised from the cell and recovered to only 9% of that in the cell-attached mode on application of CaM + ATP at 10 min after the inside out. However, immediate exposure of the excised patch to the catalytic subunit of PKA + ATP or the nonspecific phosphatase inhibitor okadaic acid significantly increased the Ca(V)1.2 channel activity recovery by CaM + ATP (114 and 96%, respectively) at 10 min. Interestingly, incubation of the excised patches with cAMP + ATP also increased CaM/ATP-induced Ca(V)1.2 channel activity recovery (108%), and this effect was blocked by the nonspecific protein kinase inhibitor K252a. The channel activity in the inside-out mode was not maintained by either catalytic subunit of PKA or cAMP + ATP in the absence of CaM, but was stably maintained in the presence of CaM for more than 40 min. These results suggest that PKA and phosphatase(s) attached on or near the Ca(V)1.2 channel regulate the basal channel activity, presumably through modulation of the dynamic CaM interaction with the channel. PMID- 26561638 TI - Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate. AB - Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with chronic kidney disease (CKD). In addition to the involvement in the progression of CKD, a recent report indicates that IS suppresses hypoxia-inducible factor (HIF)-dependent erythropoietin (EPO) production, suggesting that IS may also contribute to the progression of renal anemia. In this report, we provide evidence that aryl hydrocarbon receptor (AhR) mediates IS-induced suppression of HIF activation and subsequent EPO production. In HepG2 cells, IS at concentrations similar to the blood levels in CKD patients suppressed hypoxia- or cobalt chloride-induced EPO mRNA expression and transcriptional activation of HIF. IS also induced AhR activation, and AhR blockade resulted in abolishment of IS-induced suppression of HIF activation. The HIF transcription factor is a heterodimeric complex composed of HIF-alpha subunits (HIF-1alpha and HIF-2alpha) and AhR nuclear translocator (ARNT). IS suppressed nuclear accumulation of the HIF-alpha-ARNT complex accompanied by an increase of the AhR-ARNT complex in the nucleus, implying the involvement of interactions among AhR, HIF-alpha, and ARNT in the suppression mechanism. In rats, oral administration of indole, a metabolic precursor of IS, inhibited bleeding-induced elevation of renal EPO mRNA expression and plasma EPO concentration and strongly induced AhR activation in the liver and renal cortex tissues. Collectively, this study is the first to elucidate the detailed mechanism by which AhR plays an indispensable role in the suppression of HIF activation by IS. Hence, IS-induced activation of AhR may be a potential therapeutic target for treating renal anemia. PMID- 26561639 TI - Remodeling of the rat distal colon in diabetes: function and ultrastructure. AB - This study seeks to define and explain remodeling of the distal colon in the streptozotocin (STZ)-treated rat model of diabetes through analysis of resting and active length dependence of force production, chemical composition, and ultrastructure. Compared with untreated controls, the passive stiffness on extension of the diabetic muscle is high, and active force produced at short muscle lengths is amplified but is limited by an internal resistance to shortening. The latter are accounted for by a significant increase in collagen type 1, with no changes in types 3 and 4. In the diabetic colon, ultrastructural studies show unique, conspicuous pockets of collagen among muscle cells, in addition to a thickened basement membrane and an extracellular space filled with collagen fibers and various fibrils. Measurements of DNA and total protein content revealed that the diabetic colon underwent hypertrophy, along with a proportional increase in actin and myosin contents, with no change in the actin to-myosin ratio. Active force production per cross-sectional area was not different in the diabetic and normal muscles, consistent with the proportionality of changes in contractile proteins. The stiffness and the limit to shortening of the diabetic colon were significantly reduced by treatment with the glycation breaker alagebrium chloride (ALT-711), with no change in collagen contents. Functionally, this study shows that, in diabetes, the production of collagen type 1 and glycation increase stiffness, which limits distensibility on filling and limits shortening and expulsion of contents, both of which can be alleviated by treatment with ALT-711. PMID- 26561640 TI - Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans. AB - Calcineurin B homologous proteins (CHP) are N-myristoylated, EF-hand Ca(2+) binding proteins that bind to and regulate Na(+)/H(+) exchangers, which occurs through a variety of mechanisms whose relative significance is incompletely understood. Like mammals, Caenorhabditis elegans has three CHP paralogs, but unlike mammals, worms can survive CHP loss-of-function. However, mutants for the CHP ortholog PBO-1 are unfit, and PBO-1 has been shown to be required for proton signaling by the basolateral Na(+)/H(+) exchanger NHX-7 and for proton-coupled intestinal nutrient uptake by the apical Na(+)/H(+) exchanger NHX-2. Here, we have used this genetic model organism to interrogate PBO-1's mechanism of action. Using fluorescent tags to monitor Na(+)/H(+) exchanger trafficking and localization, we found that loss of either PBO-1 binding or activity caused NHX-7 to accumulate in late endosomes/lysosomes. In contrast, NHX-2 was stabilized at the apical membrane by a nonfunctional PBO-1 protein and was only internalized following its complete loss. Additionally, two pbo-1 paralogs were identified, and their expression patterns were analyzed. One of these contributed to the function of the excretory cell, which acts like a kidney in worms, establishing an alternative model for testing the role of this protein in membrane transporter trafficking and regulation. These results lead us to conclude that the role of CHP in Na(+)/H(+) exchanger regulation differs between apical and basolateral transporters. This further emphasizes the importance of proper targeting of Na(+)/H(+) exchangers and the critical role of CHP family proteins in this process. PMID- 26561641 TI - Hypoxia-inducible factor 3 biology: complexities and emerging themes. AB - The hypoxia-inducible factor (HIF) family has three distinct members in most vertebrates. All three HIFs consist of a unique and oxygen-labile alpha-subunit and a common and stable beta-subunit. While HIF-1 and HIF-2 function as master regulators of the transcriptional response to hypoxia, much less is known about HIF-3. The HIF-3alpha gene gives rise to multiple HIF-3alpha variants due to the utilization of different promoters, different transcription initiation sites, and alternative splicing. These HIF-3alpha variants are expressed in different tissues, at different developmental stages, and are differentially regulated by hypoxia and other factors. Recent studies suggest that different HIF-3alpha variants have different and even opposite functions. There is strong evidence that full-length HIF-3alpha protein functions as an oxygen-regulated transcription activator and that it activates a unique transcriptional program in response to hypoxia. Many HIF-3alpha target genes have been identified. While some short HIF-3alpha variants act as dominant-negative regulators of HIF 1/2alpha actions, other HIF-3alpha variants can inhibit HIF-1/2alpha actions by competing for the common HIF-beta. There are also a number of HIF-3alpha variants yet to be explored. Future studies of these naturally occurring HIF-3alpha variants will provide new and important insights into HIF biology and may lead to the development of new therapeutic strategies. PMID- 26561642 TI - Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during Hemodialysis. AB - Of the 600-700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous ((31)P) magnetic resonance spectroscopy using a 1.5 Tesla system and a surface coil placed over the gluteal muscle region. (31)P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (-30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, betaATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation. PMID- 26561644 TI - Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats. AB - Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes. PMID- 26561643 TI - Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps. AB - Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area. PMID- 26561645 TI - Hemodynamic and neurochemical determinates of renal function in chronic heart failure. AB - Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 +/- 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. PMID- 26561647 TI - Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope. AB - The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 +/- 1.3 yr of age) and 15 controls (22.8 +/- 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS. PMID- 26561646 TI - Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation. AB - The stomach-derived "hunger hormone" ghrelin increases in the circulation in direct response to time since the last meal, increasing preprandially and falling immediately following food consumption. We found previously that peripheral injection of ghrelin potently stimulates food foraging (FF), food hoarding (FH), and food intake (FI) in Siberian hamsters. It remains, however, largely unknown if central ghrelin stimulation is necessary/sufficient to increase these behaviors regardless of peripheral stimulation of the ghrelin receptor [growth hormone secretagogue receptor (GHSR)]. We injected three doses (0.01, 0.1, and 1.0 MUg) of ghrelin into the third ventricle (3V) of Siberian hamsters and measured changes in FF, FH, and FI. To test the effects of 3V ghrelin receptor blockade, we used the potent GHSR antagonist JMV2959 to block these behaviors in response to food deprivation or a peripheral ghrelin challenge. Finally, we examined neuronal activation in the arcuate nucleus and paraventricular hypothalamic nucleus in response to peripheral ghrelin administration and 3V GHSR antagonism. Third ventricular ghrelin injection significantly increased FI through 24 h and FH through day 4. Pretreatment with 3V JMV2959 successfully blocked peripheral ghrelin-induced increases in FF, FH, and FI at all time points and food deprivation-induced increases in FF, FH, and FI up to 4 h. c-Fos immunoreactivity was significantly reduced in the paraventricular hypothalamic nucleus, but not in the arcuate nucleus, following pretreatment with intraperitoneal JMV2959 and ghrelin. Collectively, these data suggest that central GHSR activation is both necessary and sufficient to increase appetitive and consummatory behaviors in Siberian hamsters. PMID- 26561649 TI - Hyperthermia, dehydration, and osmotic stress: unconventional sources of exercise induced reactive oxygen species. AB - Evidence of increased reactive oxygen species (ROS) production is observed in the circulation during exercise in humans. This is exacerbated at elevated body temperatures and attenuated when normal exercise-induced body temperature elevations are suppressed. Why ROS production during exercise is temperature dependent is entirely unknown. This review covers the human exercise studies to date that provide evidence that oxidant and antioxidant changes observed in the blood during exercise are dependent on temperature and fluid balance. We then address possible mechanisms linking exercise with these variables that include shear stress, effects of hemoconcentration, and signaling pathways involving muscle osmoregulation. Since pathways of muscle osmoregulation are rarely discussed in this context, we provide a brief review of what is currently known and unknown about muscle osmoregulation and how it may be linked to oxidant production in exercise and hyperthermia. Both the circulation and the exercising muscle fibers become concentrated with osmolytes during exercise in the heat, resulting in a competition for available water across the muscle sarcolemma and other tissues. We conclude that though multiple mechanisms may be responsible for the changes in oxidant/antioxidant balance in the blood during exercise, a strong case can be made that a significant component of ROS produced during some forms of exercise reflect requirements of adapting to osmotic challenges, hyperthermia challenges, and loss of circulating fluid volume. PMID- 26561648 TI - Neuronostatin acts via GPR107 to increase cAMP-independent PKA phosphorylation and proglucagon mRNA accumulation in pancreatic alpha-cells. AB - Neuronostatin (NST) is a recently described peptide that is produced from the somatostatin preprohormone in pancreatic delta-cells. NST has been shown to increase glucagon secretion from primary rat pancreatic islets in low-glucose conditions. Here, we demonstrate that NST increases proglucagon message in alpha cells and identify a potential mechanism for NST's cellular activities, including the phosphorylation of PKA following activation of the G protein-coupled receptor, GPR107. GPR107 is abundantly expressed in the pancreas, particularly, in rodent and human alpha-cells. Compromise of GPR107 in pancreatic alpha-cells results in failure of NST to increase PKA phosphorylation and proglucagon mRNA levels. We also demonstrate colocalization of GPR107 and NST on both mouse and human pancreatic alpha-cells. Taken together with our group's observation that NST infusion in conscious rats impairs glucose clearance in response to a glucose challenge and that plasma levels of the peptide are elevated in the fasted compared with the fed or fasted-refed state, these studies support the hypothesis that endogenous NST regulates islet cell function by interacting with GPR107 and initiating signaling in glucagon-producing alpha-cells. PMID- 26561650 TI - Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells. AB - Cellular autophagy is a prosurvival mechanism in the kidney against ischemia reperfusion injury (IRI), but the molecular pathways that activate the autophagy in ischemic kidneys are not fully understood. Clusterin (CLU) is a chaperone-like protein, and its expression is associated with kidney resistance to IRI. The present study investigated the role of CLU in prosurvival autophagy in the kidney. Renal IRI was induced in mice by clamping renal pedicles at 32 degrees C for 45 min. Hypoxia in renal tubular epithelial cell (TEC) cultures was induced by exposure to a 1% O2 atmosphere. Autophagy was determined by either light chain 3-BII expression with Western blot analysis or light chain 3-green fluorescent protein aggregation with confocal microscopy. Cell apoptosis was determined by flow cytometric analysis. The unfolded protein response was determined by PCR array. Here, we showed that autophagy was significantly activated by IRI in wild type (WT) but not CLU-deficient kidneys. Similarly, autophagy was activated by hypoxia in human proximal TECs (HKC-8) and WT mouse primary TECs but was impaired in CLU-null TECs. Hypoxia-activated autophagy was CLU dependent and positively correlated with cell survival, and inhibition of autophagy significantly promoted cell death in both HKC-8 and mouse WT/CLU-expressing TECs but not in CLU-null TECs. Further experiments showed that CLU-dependent prosurvival autophagy was associated with activation of the unfolded protein response in hypoxic kidney cells. In conclusion, these data suggest that activation of prosurvival autophagy by hypoxia in kidney cells requires CLU expression and may be a key cytoprotective mechanism of CLU in the protection of the kidney from hypoxia/ischemia-mediated injury. PMID- 26561651 TI - Alternative splice variant of the thiazide-sensitive NaCl cotransporter: a novel player in renal salt handling. AB - The thiazide-sensitive NaCl cotransporter (NCC) is an important pharmacological target in the treatment of hypertension. The human SLC12A3 gene, encoding NCC, gives rise to three isoforms. Only the third isoform has been extensively investigated. The aim of the present study was, therefore, to establish the abundance and localization of the almost identical isoforms 1 and 2 (NCC1/2) in the human kidney and to determine their functional properties and regulation in physiological conditions. Immunohistochemical analysis of NCC1/2 in the human kidney revealed that NCC1/2 localizes to the apical plasma membrane of the distal convoluted tubule. Importantly, NCC1/2 mRNA constitutes ~ 44% of all NCC isoforms in the human kidney. Functional analysis performed in the Xenopus laevis oocyte revealed that thiazide-sensitive (22)Na(+) transport of NCC1 was significantly increased compared with NCC3. Mimicking a constitutively active phosphorylation site at residue 811 (S811D) in NCC1 further augmented Na(+) transport, while a nonphosphorylatable variant (S811A) of NCC1 prevented this enhanced response. Analysis of human urinary exosomes demonstrated that water loading in human subjects significantly reduces the abundance of NCC1/2 in urinary exosomes. The present study highlights that previously underrepresented NCC1/2 is a fully functional thiazide-sensitive NaCl-transporting protein. Being significantly expressed in the kidney, it may constitute a unique route of renal NaCl reabsorption and could, therefore, play an important role in blood pressure regulation. PMID- 26561653 TI - Are dogs just like us? AB - Dogs have evolved to become the animal species most integrated with human society. Surprisingly, the origins and mechanisms of the remarkable co-evolution are still obscure and provide fuel for debates. Brain imaging studies showing up similarities and recent results implicating the hormone oxytocin also suggest that it makes sense to compare the social mind of dogs to our own. Michael Gross reports. PMID- 26561652 TI - Radiographic Reference Points Are Inaccurate With and Without a True Lateral Radiograph: The Importance of Anatomy in Medial Patellofemoral Ligament Reconstruction. AB - BACKGROUND: Studies have reported methods for radiographically delineating medial patellofemoral ligament (MPFL) femoral tunnel position on a true lateral knee radiograph. However, obtaining a true lateral fluoroscopic radiograph intraoperatively can be challenging, rendering radiographic methods for tunnel positioning potentially inaccurate. PURPOSE: To quantify the magnitude of MPFL femoral tunnel malposition that occurs on true lateral and aberrant lateral knee radiographs when using a previously reported radiographic technique for MPFL femoral tunnel localization. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten fresh-frozen cadaveric knees were dissected to expose the MPFL femoral insertion and surrounding medial knee anatomy. True lateral and aberrant lateral knee radiographs at 2.5 degrees , 5 degrees , and 10 degrees off-axis were obtained with a standard mini C-arm in 4 orientations: anterior to posterior, posterior to anterior, caudal, and cephalad. A previously reported radiographic method for MPFL femoral localization was performed on all radiographs and compared in reference to the anatomic MPFL attachment center. RESULTS: The radiographic point, as previously described, was a mean distance of 4.1 mm from the anatomic MPFL attachment on a true lateral knee radiograph. The distance between the anatomic MPFL attachment center and the radiographic point significantly increased on aberrant lateral knee radiographs with as little as 5 degrees of rotational error in 3 of 4 orientations of rotation when a standard mini C-arm was used. This corresponded to a malposition of 7.5, 9.2, and 8.1 mm on 5 degrees -aberrant radiographs in the anterior-posterior, posterior-anterior, and cephalad orientations, respectively (P < .005). In the same 3 orientations of rotation, MPFL tunnel malposition on the femur exceeded 5 mm on 2.5 degrees aberrant radiographs. CONCLUSION: The commonly utilized radiographic point, as previously described for MPFL femoral tunnel placement, results in inaccurate tunnel localization on a true lateral radiograph, and this inaccuracy is perpetuated with aberrant radiography. Aberrant lateral knee imaging of as little as 5 degrees off-axis from true lateral has a significant effect on placement of a commonly used radiographic point relative to the anatomic MPFL femoral attachment center and results in nonanatomic MPFL tunnel placement. CLINICAL RELEVANCE: This study demonstrates that radiographic localization of the MPFL femoral tunnel results in inaccurate tunnel placement on a true lateral radiograph, particularly when there is deviation from a true lateral fluoroscopic image, which can be difficult to obtain intraoperatively. Assessing anatomy directly intraoperatively, rather than relying solely on radiographs, may help avoid MPFL tunnel malposition. PMID- 26561654 TI - Jennifer Rohn. PMID- 26561655 TI - [The value of ultrasound in the follow-up of thyroid cancer]. AB - The commonly used tumour-node-metastasis (TNM) staging system is designed to predict death and not recurrence. Based on this, patients with thyroid cancer are grouped into risk categories at the time of initial treatment. However, recent guidelines proposed a novel staging system focusing on microscopic invasion into the perithyroidal tissues, neck lymph node involvement and 131I uptake outside the thyroid bed following treatment. This risk re-assessment improves the prediction of recurrent/persistent disease. The cornerstone in the follow-up is measurement of plasma-thyroglobulin concentration and ultrasound of the neck focusing on the thyroid bed and classification of lymph nodes according to their location and high risk signs. PMID- 26561656 TI - [Cancer patients' experiences contribute to more patient-centred care]. AB - In the Region of Southern Denmark, Vejle Hospital has taken the first step toward measuring patient-centred care from cancer patient's perspective. Based on results from a local patient survey this article aims to evaluate how Vejle Hospital is per-forming with regard to principles for patient-centred care in different parts of the cancer trajectory. The survey provides unique data at ward level and opportunities to initiate targeted improvement efforts for cancer patients to monitor improve-ments in patient-experienced care, which is crucial to become truly patient-centred. PMID- 26561658 TI - [Preoperative assessment and optimization]. AB - Identification of patients with high risk for post-operative complications is instrumental in all surgical specialities. Proper identification can in some cases lead to preoperative or intraoperative optimization resulting in reduced morbidity and morbidity. Several scoring systems exist for assessing overall mortality risk. Preoperative functional tests and biochemical risk markers have shown to be effective in predicting post-operative medical complications and mortality. Optimization can be done by medical interventions, improved anaesthesiological care and optimization directed towards improved communication in the surgical team. PMID- 26561657 TI - [Steroid treatment and risk of glaucoma]. AB - The risk of steroid-induced elevation of intraocular pressure and glaucoma is clinical relevant and require monitoring of patients at risk. The risk depends on route of administration, potency and individual risk factors such as primary open glaucoma (POAG), first-degree relative with POAG, age (children) and myopia. Steroid-induced elevation of intraocular pressure is most commonly associated with ocular application and systemic administration but may occur after periocular cutaneous application and nasal and inhalation therapy in patients with individual risk factors. PMID- 26561659 TI - [The use of pre-hospital tourniquets in life-threatening extremity traumas]. AB - Tourniquets have been used for centuries. They have been called lifesavers and "an invention of the evil one". 90.9% of deaths on the battlefields result from haemorrhage. Lessons learned du-ring the wars in Iraq and Afghanistan have developed the treat-ment given to hypovolaemic patients on the battlefield. Treating bleeding and hypovolaemia is now considered as the primary intervention. The tourniquet has proven to be an indis-pensable tool treating wounded soldiers, with little risk of complications. The tourniquet might also show to be a valuable asset in a pre-hospital urban setting. PMID- 26561660 TI - [Physical activity benefits patients with age-related macular degeneration]. AB - We have reviewed studies investigating the effect of physical activity on prevention of early age-related macular degeneration (AMD), progression to late AMD, and risk modulation of morbidity and mortality in patients with AMD. Regular physical activity may lower risk of developing early AMD and progression of early AMD to late AMD at a level comparable with smoking cessation or dietary supplements. Studies suggest that AMD itself is associated with physical inactivity which can result in higher morbidity levels. Patients with AMD may benefit from physical activity counselling at all stages of the disease. PMID- 26561662 TI - [Not Available]. PMID- 26561661 TI - [Pulse oximetry screening of newborns can prevent circulatory collapse caused by congenital heart defect]. AB - We present a case of total anomalous pulmonary venous drainage. Despite low oxygen saturation an eight-week-old girl had only minimal symptoms initially. She suffered collapse requiring acute surgical correction and prolonged intensive care. Her collapse and complicated post-operative course could have been avoided with earlier diagnosis. Infants with critical heart disease continue to be born undiagnosed despite prenatal ultrasound screening. There is evidence that infants with critical congenital heart defect can be detected by pulse oximetry screening, as is routine in Norway, Sweden and Finland, but not in Denmark. PMID- 26561663 TI - [In Process Citation]. PMID- 26561664 TI - [In Process Citation]. PMID- 26561665 TI - [Not Available]. PMID- 26561666 TI - [In Process Citation]. PMID- 26561667 TI - [In Process Citation]. PMID- 26561668 TI - [In Process Citation]. PMID- 26561669 TI - [Not Available]. PMID- 26561670 TI - Reply from the author. PMID- 26561671 TI - Response. PMID- 26561672 TI - Response. PMID- 26561673 TI - Response. PMID- 26561674 TI - Response. PMID- 26561675 TI - Response. PMID- 26561676 TI - Update in Interstitial Lung Disease 2014. PMID- 26561677 TI - Update in Pulmonary Vascular Diseases 2014. PMID- 26561678 TI - Plastic Bronchitis Related to Idiopathic Thoracic Lymphangiectasia. Noncontrast Magnetic Resonance Lymphography. PMID- 26561679 TI - Procedural Considerations on the Use of Polyurethane and/or Conical Cuffs. PMID- 26561680 TI - Estimating the Risk of Ventilator-associated Pneumonia as a Function of Time. PMID- 26561681 TI - Stimuli-sensitive systems--an emerging delivery system for drugs. AB - OBJECTIVES: Development of controlled and sustained drug delivery system (DDS) remains a great thrust of human beings for the successful delivery of drugs due to various drawbacks of existing systems. In order to overcome these drawbacks, various stimuli-sensitive DDSs were developed in the recent years. KEY FINDINGS: Stimuli are a state of responsiveness to sensory stimulation or excitability. Stimuli sensitive systems are those systems which deal with the changes in the physiology of body with respective to the environment changes. These systems may be very beneficial for the controlled and sustained delivery of drug in the body if proper work would be carried out on these types of systems. Controlled drug delivery became the standard criteria in modern pharmaceutical product design and an intensive research is still going on in achieving much better drug product with features like effectiveness, reliability, and safety. Many changes like photo and light, temperature, pH, ion, glucose, and redox affect the release of drug from the delivery system. These stimuli-sensitive systems are used for various purposes in various forms like in parenteral, ocular, peroral, rectal, vaginal, nasal, dermal and transdermal drug delivery. SUMMARY: Various literature surveys revealed that stimuli-sensitive DDSs can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional techniques. PMID- 26561682 TI - Cirrhosis and Its Complications. Catch this liver scarring problem early, because its effects can be life-threatening. PMID- 26561683 TI - 50 years for the Netherlands Association of Sports Medicine (VSG) and counting! PMID- 26561717 TI - Diorganyl Dichalcogenides-Promoted Nucleophilic Closure of 1,4-Diyn-3-ols: Synthesis of 2-Benzoyl Chalcogenophenes. AB - We report here the preparation of chalcogenophene derivatives via cyclization reactions of diynols promoted by diorganyl dichalcogenides and a halogen source. Different chalcogenophenes, such as 4-halo-selenophenes, 4-butylselenyl selenophenes, halo-thiophenes, and 4-methylthio-thiophenes, were selectively prepared in good yields from the same starting materials. The results revealed that the halogen source had a significant effect on the proportion of 4-bromo selenophenes and 4-butylselenyl-selenophenes. The best yields of 4-iodo selenophenes were obtained with iodine as a halogen source, while the use of NBS gave exclusively the 4-butylselenyl-selenophenes. The experiments also revealed that the cyclization reaction to form 4-halo-thiophene derivatives can also be controlled changing the ratios of reagents. The 4-iodo-thiophenes were exclusively obtained by using dimethyl disulfide (2.0 equiv) and iodine (1.5 equiv), while the 4-bromo-thiophenes were obtained when the reaction was carried out with a 1.5 molar ratio of dimethyl disulfide and a halogen source. In addition, the reaction of diynols with an excess of dimethyl disulfide in the presence of NBS gave the 4-methylthio-thiophenes as sole products. We also studied the application of chalcogenophenes obtained as starting materials in the Suzuki, Sonogashira, and Ullmann cross-coupling reactions. PMID- 26561718 TI - pi-Conjugated Organometallic Isoindigo Oligomer and Polymer Chromophores: Singlet and Triplet Excited State Dynamics and Application in Polymer Solar Cells. AB - An isoindigo based pi-conjugated oligomer and polymer that contain cyclometalated platinum(II) "auxochrome" units were subjected to photophysical characterization, and application of the polymer in bulk heterojunction polymer solar cells with PCBM acceptor was examined. The objective of the study was to explore the effect of the heavy metal centers on the excited state properties, in particular, intersystem crossing to a triplet (exciton) state, and further how this would influence the performance of the organometallic polymer in solar cells. The materials were characterized by electrochemistry, ground state absorption, emission, and picosecond-nanosecond transient absorption spectroscopy. Electrochemical measurements indicate that the cyclometalated units have a significant impact on the HOMO energy level of the chromophores, but little effect on the LUMO, which is consistent with localization of the LUMO on the isoindigo acceptor unit. Picosecond-nanosecond transient absorption spectroscopy reveals a transient with ~100 ns lifetime that is assigned to a triplet excited state that is produced by intersystem crossing from a singlet state on a time scale of ~130 ps. This is the first time that a triplet state has been observed for isoindigo pi-conjugated chromophores. The performance of the polymer in bulk heterojunction solar cells was explored with PC61BM as an acceptor. The performance of the cells was optimum at a relatively high PCBM loading (1:6, polymer:PCBM), but the overall efficiency was relatively low with power conversion efficiency (PCE) of 0.22%. Atomic force microscopy of blend films reveals that the length scale of the phase separation decreases with increasing PCBM content, suggesting a reason for the increase in PCE with acceptor loading. Energetic considerations show that the triplet state in the polymer is too low in energy to undergo charge separation with PCBM. Further, due to the relatively low LUMO energy of the polymer, charge transfer from the singlet to PCBM is only weakly exothermic, which is believed to be the reason that the photocurrent efficiency is relatively low. PMID- 26561719 TI - Varitatin A, a Highly Modified Fatty Acid Amide from Penicillium variabile Cultured with a DNA Methyltransferase Inhibitor. AB - A new, highly modified fatty acid amide, varitatin A (1), was isolated from the fungus Penicillium variabile HXQ-H-1 cultivated with the DNA methyltransferase inhibitor 5-azacytidine. The structure including the absolute configuration of 1 was established by analysis of NMR and MS data, together with chemical degradation and Mosher's method based on MPA esters. Compound 1 showed cytotoxicity against HCT-116 cells with an IC50 value of 2.8 MUM and also inhibited the effects of protein tyrosine kinases. PMID- 26561720 TI - A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy. AB - Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer "immuno-chemotherapy". Compound 2 effectively kills hormone dependent, cisplatin-resistant human ovarian cancer cells, inhibiting IDO by transcriptional deregulation of the autocrine-signaling loop IDO-AHR-IL6, which blocks kynurenine production and promotes T-cell proliferation. Additionally, 1 and 2 display low toxicity in mice and are stable in blood. To our knowledge, this construct is the first Pt drug candidate with immune checkpoint blockade properties. PMID- 26561721 TI - Lower-Body Muscle Structure and Jump Performance of Stronger and Weaker Surfing Athletes. AB - PURPOSE: To identify whether there are any significant differences in the lower body muscle structure and countermovement-jump (CMJ) and squat-jump (SJ) performance between stronger and weaker surfing athletes. METHODS: Twenty elite male surfers had their lower-body muscle structure assessed with ultrasonography and completed a series of lower-body strength and jump tests including isometric midthigh pull (IMTP), CMJ, and SJ. Athletes were separated into stronger (n = 10) and weaker (n = 10) groups based on IMTP performance. RESULTS: Large significant differences were identified between the groups for vastus lateralis (VL) thickness (P = .02, ES = 1.22) and lateral gastrocnemius (LG) pennation angle (P = .01, ES = 1.20), and a large nonsignificant difference was identified in LG thickness (P = .08, ES = 0.89). Furthermore, significant differences were present between the groups for peak force, relative peak force, and jump height in the CMJ and SJ (P < .01-.05, ES = 0.90-1.47) and eccentric peak velocity, as well as vertical displacement of the center of mass during the CMJ (P < .01, ES = 1.40 1.41). CONCLUSION: Stronger surfing athletes in this study had greater VL and LG thickness and LG pennation angle. These muscle structures may explain their better performance in the CMJ and SJ. A unique finding in this study was that the stronger group appeared to better use their strength and muscle structure for braking as they had significantly higher eccentric peak velocity and vertical displacement during the CMJ. This enhanced eccentric phase may have resulted in a greater production and subsequent utilization of stored elastic strain energy that led to the significantly better CMJ performance in the stronger group. PMID- 26561722 TI - Race/Ethnic Differences in Birth Size, Infant Growth, and Body Mass Index at Age Five Years in Children in Hawaii. AB - BACKGROUND: Factors at birth and infancy may increase risk of being overweight in childhood. The aim of this study was to examine the relationship of birth size and infant growth (2-24 months) with BMI at age 5 years in a multiethnic population. METHODS: This was a retrospective study (using electronic medical records of a health maintenance organization in Hawaii) of singleton children born in 2004-2005, with linked maternal and birth information, infant weights (n = 597) and lengths (n = 473) in the first 2 years, and BMI measures at age 5 years (n = 894). Multiple regression models were used to estimate the association of BMI at age 5 years with birth size and infant growth. RESULTS: Birth weight was positively associated with BMI at age 5 years, adjusting for gestational age, sex, race/ethnicity, and maternal prepregnancy weight, age, education, and smoking. A greater change in infant weight was associated with a higher BMI at age 5 years, though the effect of birth weight on BMI was neither mediated nor modified by infant growth rate. Birth weight, change in infant weight, and BMI at age 5 years varied by race/ethnicity. Change in infant BMI in the first 2 years was higher in other Pacific Islanders and whites (Delta = 0.966; confidence interval [CI] = 0.249-1.684; p = 0.02) than in Asian, other, and part Native Hawaiian race/ethnic groups. CONCLUSIONS: Early biological measures of birth weight and infant weight gain varied by race/ethnicity and positively predicted BMI at age 5 years. PMID- 26561723 TI - Airborne allergens induce protease activated receptor-2-mediated production of inflammatory cytokines in human gingival epithelium. AB - OBJECTIVE: In reaching the airways inhaled allergens pass through and contact with the oral mucosa. Although they are often responsible for initiating asthmatic attacks, it is unknown whether airborne allergens can also trigger chronic inflammation of gingival epithelial cells leading to chronic periodontitis. In this study, we investigated the inflammatory responses of human gingival epithelial cells (HGECs) to airborne allergens, particularly German cockroach extract (GCE) with a focus on calcium signaling. DESIGN: HGECs isolated from healthy donors were stimulated with GCE. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured with Fura-2-acetoxymethyl ester (Fura-2/AM) staining. Expression of inflammatory cytokines interleukin (IL)-8, IL-1beta, IL-6, and NOD like receptor family, pyridine domain-containing (NLRP) 3 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: GCE promoted increase in the [Ca(2+)]i in a dose-dependent manner. Depletion of endoplasmic reticulum (ER) Ca(2+) by the ER Ca(2+) ATPase inhibitor thapsigargin (Tg) but not the depletion of extracellular Ca(2+) abolished the GCE-induced increase in [Ca(2+)]i. Treatment of phospholipase C (PLC) inhibitor (U73122) or 1,4,5 trisinositolphosphate (IP3) receptor inhibitor (2-APB) also prevented GCE-induced increase in [Ca(2+)]i. Protease activated receptor (PAR)-2 activation mainly mediated the GCE-induced increase in [Ca(2+)]i and enhanced the expression of IL 8, NLRP3, IL-1beta, and IL-6 in HGECs. CONCLUSIONS: GCE activates PAR-2, which can induce PLC/IP3-dependent Ca(2+) signaling pathway, ultimately triggering inflammation via the production of pro-inflammatory cytokines such as IL-1beta, IL-6, IL-8, and NLRP 3 in HGECs. PMID- 26561724 TI - Surface Porphyrins Metalate with Zn Ions from Solution. AB - Controlling the metalation of surface porphyrins is a critical process in porphyrin-based devices. Indeed, surface porphyrins are known to metalate in ultrahigh vacuum from codeposited metal atoms or substrate atoms; however, it is not yet known if surface porphyrins could metalate from ions in solution, that is, the most likely environment for porphyrin-based devices. Using X-ray photoelectron spectroscopy we have studied the metalation of monolayers and multilayers of a free-base tetraphenyl porphyrin adsorbed on Au(111) with ions in solution. We found that full metalation with Zn(2+) can be achieved already at room temperature in contrast with the elevated temperatures required for metalation with codeposited metal atoms. PMID- 26561725 TI - Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during in vitro release. AB - Polymeric microparticles (MPs)-in-gel formulations for extended delivery of octreotide were developed. We investigated influence of polymer composition on acylation of octreotide and kinetics of release during in vitro release from biodegradable polymeric formulations. Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA) and polyethylene glycol (PEG) based triblock (TB~PCL10k-PEG2k-PCL10k) and pentablock (PBA~PLA3k-PCL7k-PEG2k-PCL7k-PLA3k and PBB~PGA3k-PCL7k-PEG2k-PCL7k-PGA3k) polymers were investigated. Octreotide was encapsulated in MPs using methanol-oil/water emulsion solvent evaporation method. The particles were characterized for size, morphology, encapsulation efficiency, drug loading and in vitro release. Release samples were subjected to HPLC analysis for quantitation and HPLC-MS analysis for identification of native and chemically modified octreotide adducts. Entrapment efficiency of methanol oil/water method with TB, PBA and PBB polymers were 45%, 60%, and 82%, respectively. A significant fraction of released octreotide was acylated from lactide and glycolide based PBA (53%) and PBB (92%) polymers. Substantial amount of peptide was not released from PBB polymers after 330 days of incubation. Complete release of octreotide was achieved from TB polymer over a period of 3 months with minimal acylation of peptide (13%). PCL based polymers resulted in minimal acylation of peptide and hence may be suitable for extended peptide and protein delivery. Conversely, polymers having PLA and PGA blocks may not be appropriate for peptide delivery due to acylation and incomplete release. PMID- 26561726 TI - Optimization, physicochemical characterization and in vivo assessment of spray dried emulsion: A step toward bioavailability augmentation and gastric toxicity minimization. AB - The limited solubility of BCS class II drugs diminishes their dissolution and thus reduces their bioavailability. Our aim in this study was to develop and optimize a spray dried emulsion containing indomethacin as a model for Class II drugs, Labrasol(r)/Transuctol(r) mixture as the oily phase, and maltodextrin as a solid carrier. The optimization was carried out using a 2(3) full factorial design based on two independent variables, the percentage of carrier and concentration of Poloxamer(r) 188. The effect of the studied parameters on the spray dried yield, loading efficiency and in vitro release were thoroughly investigated. Furthermore, physicochemical characterization of the optimized formulation was performed. In vivo bioavailability, ulcerogenic capability and histopathological features were assessed. The results obtained pointed out that poloxamer 188 concentration in the formulation was the predominant factor affecting the dissolution release, whereas the drug loading was driven by the carrier concentration added. Moreover, the yield demonstrated a drawback by increasing both independent variables studied. The optimized formulation presented a complete release within two minutes thus suggesting an immediate release pattern as well, the formulation revealed to be uniform spherical particles with an average size of 7.5MUm entrapping the drug in its molecular state as demonstrated by the DSC and FTIR studies. The in vivo evaluation, demonstrated a 10-fold enhancement in bioavailability of the optimized formulation, with absence of ulcerogenic side effect compared to the marketed product. The results provided an evidence for the significance of spray dried emulsion as a leading strategy for improving the solubility and enhancing the bioavailability of class II drugs. PMID- 26561727 TI - Impact of the nature and concentration of plasticizers on the ability of PVC to sorb drug. AB - The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizer's nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH(r) plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC. PMID- 26561728 TI - Large, Tunable Magnetoresistance in Nonmagnetic III-V Nanowires. AB - Magnetoresistance, the modulation of resistance by magnetic fields, has been adopted and continues to evolve in many device applications including hard-disk, memory, and sensors. Magnetoresistance in nonmagnetic semiconductors has recently raised much attention and shows great potential due to its large magnitude that is comparable or even larger than magnetic materials. However, most of the previous work focus on two terminal devices with large dimensions, typically of micrometer scales, which severely limit their performance potential and more importantly, scalability in commercial applications. Here, we investigate magnetoresistance in the impact ionization region in InGaAs nanowires with 20 nm diameter and 40 nm gate length. The deeply scaled dimensions of these nanowires enable high sensibility with less power consumption. Moreover, in these three terminal devices, the magnitude of magnetoresistance can be tuned by the transverse electric field controlled by gate voltage. Large magnetoresistance between 100% at room temperature and 2000% at 4.3 K can be achieved at 2.5 T. These nanoscale devices with large magnetoresistance offer excellent opportunity for future high-density large-scale magneto-electric devices using top-down fabrication approaches, which are compatible with commercial silicon platform. PMID- 26561729 TI - Air Pollution Exposure Model for Individuals (EMI) in Health Studies: Evaluation for Ambient PM2.5 in Central North Carolina. AB - Air pollution health studies of fine particulate matter (diameter <=2.5 MUm, PM2.5) often use outdoor concentrations as exposure surrogates. Failure to account for variability of indoor infiltration of ambient PM2.5 and time indoors can induce exposure errors. We developed and evaluated an exposure model for individuals (EMI), which predicts five tiers of individual-level exposure metrics for ambient PM2.5 using outdoor concentrations, questionnaires, weather, and time location information. We linked a mechanistic air exchange rate (AER) model to a mass-balance PM2.5 infiltration model to predict residential AER (Tier 1), infiltration factors (Tier 2), indoor concentrations (Tier 3), personal exposure factors (Tier 4), and personal exposures (Tier 5) for ambient PM2.5. Using cross validation, individual predictions were compared to 591 daily measurements from 31 homes (Tiers 1-3) and participants (Tiers 4-5) in central North Carolina. Median absolute differences were 39% (0.17 h(-1)) for Tier 1, 18% (0.10) for Tier 2, 20% (2.0 MUg/m(3)) for Tier 3, 18% (0.10) for Tier 4, and 20% (1.8 MUg/m(3)) for Tier 5. The capability of EMI could help reduce the uncertainty of ambient PM2.5 exposure metrics used in health studies. PMID- 26561731 TI - Measurement of Femoral Vein Diameter by Ultrasound to Estimate Central Venous Pressure. AB - RATIONALE: Central venous pressure (CVP) can be estimated by ultrasound of the inferior vena cava (IVC), but imaging the IVC is sometimes challenging. The femoral vein is easily imaged by ultrasound and might therefore provide an alternate target for estimating CVP. OBJECTIVES: To assess femoral vein diameter (FVD) measured by ultrasound imaging for estimating CVP. METHODS: We prospectively measured CVP and FVD in 97 patients. Receiver operating characteristic curves were used to assess the ability of FVD to predict specific CVP values: less than 10 mm Hg, less than 8 mm Hg (low CVP), and greater than 12 mm Hg (high CVP). Interobserver variability of FVD measurement was assessed in 20 patients. MEASUREMENTS AND MAIN RESULTS: There was moderate correlation between FVD and CVP (r = 0.66, P < 0.001). FVD less than or equal to 0.8 cm was the best predictor of CVP < 10 mm Hg, with an area under the curve (AUC) of 0.894 and a 95% confidence interval (CI) of 0.82 to 0.97. FVD less than or equal to 0.7 cm performed best for predicting low CVP (AUC = 0.97; 95% CI, 0.94-0.99) and FVD greater than or equal to 1.0 cm for high CVP (AUC = 0.80; 95% CI, 0.72-0.89). However, FVD greater than or equal to 1.2 cm had the greatest specificity (94%) for high CVP. Interobserver variability in FVD measurements was 8.3 +/- 7.2%. CONCLUSIONS: The results of this exploratory study suggest that the accuracy of FVD measured by ultrasound imaging for estimating CVP is comparable to that which has been reported for ultrasound measurement of IVC diameter. FVD may provide an alternative approach when the IVC is difficult to image. Additional studies on other cohorts of patients are warranted to validate our proposed FVD cutoff values for predicting low and high CVP. PMID- 26561730 TI - Cell density regulates cancer metastasis via the Hippo pathway. AB - Metastatic spread of cancer cells from the primary tumor site to distant organs is the major cause of death in cancer patients. To disseminate, cancer cells detach from the primary tumor, enter the blood stream and extravasate at distant organ sites such as the liver, lung, bone or brain. While cancer cells are known to evade contact inhibition during growth in culture, we found that cell density is still sensed and can signal through the Hippo pathway effectors LATS1 and YAP. These effectors control cancer cell invasive behavior into stromal tissues, expression of cytokines that recruit inflammatory cells and progression toward metastatic spread. In this perspective, we discuss the drivers and the significance of pathways controlled by cell growth density. PMID- 26561732 TI - Feruloyl glycerol and 1,3-diferuloyl glycerol antioxidant behavior in phospholipid vesicles. AB - Feruloyl-sn-glycerol (FG) and 1,3-diferuloyl-sn-glycerol (F2G), the by-product of biocatalytic transesterification soybean oil and ethyl ferulate, were examined for their behavior in phospholipid vesicles. Based on absorbance and fluorescence methods, FG and F2G both were found to partition into vesicles and incorporate well into 1,2-dioleoylphosphocholine (DOPC) vesicles. FG and F2G incorporation resulted in vesicles that were as or slightly more stable than the unloaded vesicles. FG and F2G both demonstrated the ability to maintain antioxidant properties within the lipid bilayer. Bilayer depth analysis was conducted using the parallax method and molecular modeling. PMID- 26561733 TI - A randomized controlled trial of guided internet-delivered cognitive behaviour therapy for older adults with generalized anxiety. AB - This study aimed to establish the efficacy of guided Internet-delivered cognitive behaviour therapy (ICBT) for older adults with generalized anxiety disorder (GAD) or subclinical GAD. Participants were randomized to receive seven modules of ICBT (n=24) or to a waiting list condition (WLC; n=22). Faster improvements in symptoms of anxiety and depression were observed for participants in the ICBT condition relative to the WLC, with large between-group effect sizes on the Generalized anxiety disorder-7 (d=.85) and the Patient health questionnaire (d=1.17) obtained at post-treatment. Further reduction in generalized anxiety symptoms was reported over the one-month follow-up. Treatment effects were replicated when control participants subsequently underwent treatment. Higher ratings of treatment credibility, but not expectancy, prior to ICBT predicted improvements over time. The results support the efficacy of ICBT as treatment for older adults with GAD. PMID- 26561734 TI - Latent profiles of DSM-5 PTSD symptoms and the "Big Five" personality traits. AB - Typologies of DSM-5 PTSD symptoms and personality traits were evaluated in regard to coping styles and treatment preferences using data from 1266 trauma-exposed military veterans of which the majority were male (n=1097; weighted 89.6%). Latent profile analyses indicated a best-fitting 5-class solution; PTSD asymptomatic and emotionally stable (C1); predominant re-experiencing and avoidance symptoms and less emotionally stable (C2); subsyndromal PTSD (C3); predominant negative alterations in mood/cognitions and combined internalizing externalizing traits (C4); and high PTSD severity and combined internalizing externalizing traits (C5). Compared to C5, C1 members were less likely to use self-distraction, denial, and substance use and more likely to use active coping; C2 and C4 members were less likely to use denial and more likely to use behavioral disengagement; C3 members were less likely to use denial and instrumental coping and more likely to use active coping; most classes were less likely to seek mental health treatment. Compared to C1, C2 members were more likely to use self-distraction, substance use, behavioral disengagement and less likely to use active coping; C3 members were more likely to use self-distraction, and substance use, and less likely to use positive reframing, and acceptance; and C4 members were more likely to use denial, substance use, emotional support, and behavioral disengagement, and less likely to use active coping, positive reframing, and acceptance; all classes were more likely to seek mental health treatment. Emotional stability was most distinguishing of the typologies. Other implications are discussed. PMID- 26561735 TI - Analysis of Homogeneous Water Oxidation Catalysis with Collector-Generator Cells. AB - A collector-generator (C-G) technique has been applied to determine the Faradaic efficiencies for electrocatalytic O2 production by the homogeneous water oxidation catalysts Ru(bda)(isoq)2 (1; bda = 2,2'-bipyridine and isoq = isoquinoline) and [Ru(tpy)(bpz)(OH2)](2+) (2; tpy = 2,2':6',2"-terpyridine and bpz = 2,2'-bipyrazine). This technique uses a custom-fabricated cell consisting of two fluorine-doped tin oxide (FTO) working electrodes separated by 1 mm with the conductive sides facing each other. With a catalyst in solution, water oxidation occurs at one FTO electrode under a sufficient bias to drive O2 formation by the catalyst; the O2 formed then diffuses to the second FTO electrode poised at a potential sufficiently negative to drive O2 reduction. A comparison of the current versus time response at each electrode enables determination of the Faradaic efficiency for O2 production with high concentrations of supporting electrolyte important for avoiding capacitance effects between the electrodes. The C-G technique was applied to electrocatalytic water oxidation by 1 in the presence of the electron-transfer mediator Ru(bpy)3(2+) in both unbuffered aqueous solutions and with the added buffer bases HCO3(-), HPO4(2-), imidazole, 1-methylimidazole, and 4-methoxypyridine. HCO3(-) and HPO4(2-) facilitate water oxidation by atom-proton transfer (APT), which gave Faradaic yields of 100%. With imidazole as the buffer base, coordination to the catalyst inhibited water oxidation. 1-Methylimidazole and 4-methoxypyridine gave O2 yields of 55% and 76%, respectively, with the lower Faradaic efficiencies possibly due to competitive C-H oxidation of the bases. O2 evolution by catalyst 2 was evaluated at pH 12 with 0.1 M PO4(3-) and at pH 7 in a 0.1 M H2PO4( )/HPO4(2-) buffer. At pH 12, at an applied potential of 0.8 V vs SCE, water oxidation by the Ru(IV)(O)(2+) form of the catalyst gave O2 in 73% yield. In a pH 7 solution, water oxidation at 1.4 V vs SCE, which is dominated by Ru(V)(O)(3+), gave O2 with an efficiency of 100%. The lower efficiency for Ru(IV)(O)(2+) at pH 12 may be due to competitive oxidation of a polypyridyl ligand. PMID- 26561736 TI - Association of Surgeon Volume With Outcomes and Cost Savings Following Thyroidectomy: A National Forecast. AB - IMPORTANCE: Incidence of thyroidectomies is continuing to increase. Identifying factors associated with favorable outcomes can lead to cost savings. OBJECTIVE: To assess the association of surgeon volume with clinical outcomes and costs of thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis performed in October of 2014 of adult (>= 18 years) inpatients in US community hospitals using the Nationwide Inpatient Sample for the years 2003 through 2009. EXPOSURES: Thyroidectomy. MAIN OUTCOMES AND MEASURES: Complications, length of stay, and cost following thyroidectomy in relation to surgeon volume. Surgeon volumes were stratified into low (1-3 thyroidectomies per year), intermediate (4 29 thyroidectomies per year), and high (>= 30 thyroidectomies per year). RESULTS: A total of 77,863 patients were included. Procedures performed by low-volume surgeons were associated with a higher risk of postoperative complications compared with high-volume surgeons (15.8% vs 7.7%; OR, 1.55 [95% CI, 1.19-2.03]; P = .001). Mean (SD) hospital cost was significantly associated with surgeon volume (high volume, $6662.69 [$409.31]; intermediate volume, $6912.41 [$137.20]; low volume, $10,396.21 [$345.17]; P < .001). During the study period, if all operations performed by low-volume surgeons had been selectively referred to intermediate- or high-volume surgeons, savings of 11.2% or 12.2%, respectively, would have been incurred. On the basis of the cost growth rate, greater savings are forecasted for high-volume surgeons. With a conservative assumption of 150,000 thyroidectomies per year in the United States, referral of all patients to intermediate- or high-volume surgeons would produce savings of $2.08 billion or $3.11 billion, respectively, over a span of 14 years. CONCLUSIONS AND RELEVANCE: A surgeon's expertise (measured by surgical volume of procedures per year) is associated with favorable clinical as well as financial outcomes. Our model estimates that considerable cost savings are attainable if higher-volume surgeons perform thyroid procedures in the United States. PMID- 26561737 TI - Artemisinin, a miracle of traditional Chinese medicine. AB - The 2015 Nobel Prize in Physiology or Medicine, shared by Professor Youyou Tu, focused worldwide attention on artemisinin, a natural product antimalarial drug inspired by traditional Chinese medicine (TCM). This is the first Nobel Prize in natural sciences presented to a Chinese scientist for her impactful research work in China in collaboration with other Chinese scientists. We are delighted to provide the background and implications of the discovery of artemisinin, along with our personal viewpoints toward the affordability of modern medicines from natural products. PMID- 26561738 TI - NMR of (133)Cs(+) in stretched hydrogels: One-dimensional, z- and NOESY spectra, and probing the ion's environment in erythrocytes. AB - (133)Cs nuclear magnetic resonance (NMR) spectroscopy was conducted on (133)Cs(+) in gelatin hydrogels that were either relaxed or stretched. Stretching generated a septet from this spin-7/2 nucleus, and its nuclear magnetic relaxation was studied via z-spectra, and two-dimensional nuclear Overhauser (NOESY) spectroscopy. Various spectral features were well simulated by using Mathematica and the software package SpinDynamica. Spectra of CsCl in suspensions of human erythrocytes embedded in gelatin gel showed separation of the resonances from the cation inside and outside the cells. Upon stretching the sample, the extracellular (133)Cs(+) signal split into a septet, while the intracellular peak was unchanged, revealing different alignment/ordering properties of the environment inside and around the cells. Differential interference contrast light microscopy confirmed that the cells were stretched when the overall sample was elongated. Analysis of the various spectral features of (133)Cs(+) reported here opens up applications of this K(+) congener for studies of cation-handling by metabolically-active cells and tissues in aligned states. PMID- 26561739 TI - Characteristics of Cell-Penetrating Peptide/Nucleic Acid Nanoparticles. AB - Nucleic acids are highly promising candidates for the treatment of various genetic diseases. However, due to the large size and negative charge, nucleic acids are not efficiently taken up by cells, and thus, their clinical potential remains limited so far. Therefore, various delivery vehicles have been designed to assist the cellular uptake of nucleic acids. Among these, cell-penetrating peptides (CPPs) have gained increasing popularity as efficient and nontoxic delivery vectors. CPPs can be coupled to nucleic acids either by covalent or noncovalent association. Noncovalent coupling, which is based on the formation of nanoparticle-like nanocomplexes (NP), has received much attention in recent years, and the number of studies employing the strategy is explosively increasing due to the high therapeutic potential. However, the properties of CPP/nucleic acid NPs have not been characterized in sufficient detail yet. We performed a comprehensive analysis of the size and morphology of nucleic acid nanoparticles with novel transfection peptides, PepFects (PFs) and NickFects (NFs), using negative staining transmission electron microscopy (TEM). In addition, we examined whether the attachment of fluorescence or (nano)gold label to nucleic acid affects the nanocomplex formation or its morphology. We demonstrated that transportan-10-based new generation CPPs from PF and NF families condense nucleic acids to NPs of homogeneous size and shape. The size and shape of assembled nanoparticles depend on the type of the complexed nucleic acid and the sequence of the used peptide, whereas the label on the nucleic acid does not influence the gross characteristics of formed NPs. PMID- 26561741 TI - Feed supplemented with polyphenolic byproduct from olive mill wastewater processing improves the redox status in blood and tissues of piglets. AB - In the present study, a polyphenolic byproduct from olive mill wastewater (OMWW) was used for making piglet feed with antioxidant activity. For examining the antioxidant capacity of the feed, 30 piglets of 20 d old were divided into two groups receiving basal or experimental feed for 30 d. Blood and tissue samples were drawn at days 2, 20, 35 and 50 post-birth. The tissues collected were brain, heart, kidney, liver, lung, quadriceps muscle, pancreas, spleen and stomach. The antioxidant effects of the experimental feed were assessed by measuring oxidative stress biomarkers in blood and tissues. The oxidative stress markers were total antioxidant capacity (TAC), glutathione (GSH), catalase activity (CAT), protein carbonyls (CARB) and thiobarbituric acid reactive species (TBARS). The results showed that piglets fed with diet supplemented with OMWW polyphenols had significantly increased antioxidant mechanisms in blood and the majority of the tested tissues as shown by increases in TAC, CAT and GSH compared to control group. Moreover, piglets fed with the experimental feed exhibited decreased oxidative stress-induced damage to lipids and proteins as shown by decreases in TBARS and CARB respectively. This is the first study in which OMWW polyphenols were used for making pig feed with antioxidant activity. PMID- 26561742 TI - Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile. AB - Two series of new thiazolidin-4-one derivatives 4a-c and 8a-e were designed and prepared. All the synthesized compounds were evaluated for their in vitro COX-2 selectivity and anti-inflammatory activity in vivo. Compounds 8c and 8d showed the best overall in vitro COX-2 selectivity (selectivity indexes of 4.56 and 5.68 respectively) and in vivo activities (edema inhibition %=61.8 and 67 after 3h, respectively) in comparison with the reference drug celecoxib (S.I.=7.29, edema inhibition %=60 after 3h). In addition, 8c and 8d were evaluated for their mean effective anti-inflammatory doses (ED50=27.7 and 18.1 MUmol/kg respectively, celecoxib ED50=28.2 MUmol/kg) and ulcerogenic liability (reduction in ulcerogenic potential versus celecoxib=85%, 92% respectively. Molecular docking studies were performed and the results were in agreement with that obtained from the in vitro COX inhibition assays. PMID- 26561740 TI - Critical review of resveratrol in xenobiotic-induced hepatotoxicity. AB - Use of natural products is increasingly popular. In fact, many patients with liver diseases self-medicate with herbal supplements. Resveratrol (RSV), in particular, is a common natural product that can reduce injury in experimental models of liver disease. Xenobiotic hepatotoxicity is a particularly important area-of-need for therapeutics. Drug-induced liver injury, for example, is the most common cause of acute liver failure (ALF) and ALF-induced deaths in many countries. Importantly, RSV protects against hepatotoxicity in animal models in vivo caused by several drugs and chemicals and may be an effective intervention. Although many mechanisms have been proposed to explain the protection, not all are consistent with other data. Furthermore, RSV suffers from other issues, including limited bioavailability due to extensive hepatic metabolism. The purpose of this article is to summarize recent findings on the protective effects of RSV in xenobiotic-induced liver injury and other forms of liver injury and to provide a critical review of the underlying mechanisms. New mechanisms that are more consistent with data emerging from the toxicology field are suggested. Efforts to move RSV into clinical use are also considered. Overall, RSV is a promising candidate for therapeutic use, but additional studies are needed to better understand its effects. PMID- 26561744 TI - The regulation of exosome function in the CNS: implications for neurodegeneration. AB - Exosomes are nanovesicles, generally 50 to 90 nm in diameter, that correspond to the intraluminal vesicles of the endosomal multivesicular bodies and are secreted upon fusion of multivesicular bodies with the plasma membrane. Their molecular content is highly selected and includes not only specific proteins and lipids, but also RNA species, such as messenger RNAs (mRNAs) and microRNAs (miRNAs), which are delivered and active in target cells. As they are released in body fluids, exosomes can shuttle molecules for long distances. In the CNS they have been shown to regulate neuronal development and regeneration, and to modulate synaptic functions. In neurodegenerative diseases, they have an important role in propagating neurotoxic misfolded protein from one cell to another and, as recent data show, possibly other molecules contributing to neurotoxicity. Some exosomal lipids such as gangliosides GM1 and GM3 enhance the aggregation of alpha synuclein, and RNA exosomal cargo is also altered during pathologies such as Alzheimer's disease, prion diseases and amyotrophic lateral sclerosis. The aim of this review is to focus on the regulation of CNS exosomal function and highlight pathways that might have a role in the neurodegenerative process. The identification of the novel exosomal molecules involved in neurodegenerative diseases could provide important insights into the pathogenesis and contribute to the finding of novel diagnostic biomarkers and therapeutic approaches. PMID- 26561743 TI - Species detection using HyBeacon((r)) probe technology: Working towards rapid onsite testing in non-human forensic and food authentication applications. AB - Identifying individual species or determining species' composition in an unknown sample is important for a variety of forensic applications. Food authentication, monitoring illegal trade in endangered species, forensic entomology, sexual assault case work and counter terrorism are just some of the fields that can require the detection of the biological species present. Traditional laboratory based approaches employ a wide variety of tools and technologies and exploit a number of different species specific traits including morphology, molecular differences and immuno-chemical analyses. A large number of these approaches require laboratory based apparatus and results can take a number of days to be returned to investigating authorities. Having a presumptive test for rapid identification could lead to savings in terms of cost and time and allow sample prioritisation if confirmatory testing in a laboratory is required later. This model study describes the development of an assay using a single HyBeacon((r)) probe and melt curve analyses allowing rapid screening and authentication of food products labelled as Atlantic cod (Gadus morhua). Exploiting melt curve detection of species specific SNP sites on the COI gene the test allows detection of a target species (Atlantic cod) and closely related species which may be used as substitutes. The assay has been designed for use with the Field Portable ParaDNA system, a molecular detection platform for non-expert users. The entire process from sampling to result takes approximately 75min. Validation studies were performed on both single source genomic DNA, mixed genomic DNA and commercial samples. Data suggests the assay has a lower limit of detection of 31 pg DNA. The specificity of the assay to Atlantic cod was measured by testing highly processed food samples including frozen, defrosted and cooked fish fillets as well as fish fingers, battered fish fillet and fish pie. Ninety-six (92.7%) of all Atlantic cod food products, tested, provided a correct single species result with the remaining samples erroneously identified as containing non-target species. The data shows that the assay was quick to design and characterise and is also capable of yielding results that would be beneficial in a variety of fields, not least the authentication of food. PMID- 26561745 TI - Prone position for acute respiratory failure in adults. AB - BACKGROUND: Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes. OBJECTIVES: The objectives of this review are (1) to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation, and (2) to supplement previous systematic reviews on prone ventilation for hypoxaemic respiratory failure in an adult population. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1), Ovid MEDLINE (1950 to 31 January 2014), EMBASE (1980 to 31 January 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 31 January 2014) and Latin American Caribbean Health Sciences Literature (LILACS) (1992 to 31 January 2014) in Ovid MEDLINE for eligible randomized controlled trials. We also searched for studies by handsearching reference lists of relevant articles, by contacting colleagues and by handsearching published proceedings of relevant journals. We applied no language constraints, and we reran the searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. We added five new studies of potential interest to the list of "Studies awaiting classification" and will incorporate them into formal review findings during the review update. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that examined the effects of prone position versus supine/semi recumbent position during conventional mechanical ventilation in adult participants with acute hypoxaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all trials identified by the search and assessed them for suitability, methods and quality. Two review authors extracted data, and three review authors reviewed the data extracted. We analysed data using Review Manager software and pooled included studies to determine the risk ratio (RR) for mortality and the risk ratio or mean difference (MD) for secondary outcomes; we also performed subgroup analyses and sensitivity analyses. MAIN RESULTS: We identified nine relevant RCTs, which enrolled a total of 2165 participants (10 publications). All recruited participants suffered from disorders of lung function causing moderate to severe hypoxaemia and requiring mechanical ventilation, so they were fairly comparable, given the heterogeneity of specific disease diagnoses in intensive care. Risk of bias, although acceptable in the view of the review authors, was inevitable: Blinding of participants and carers to treatment allocation was not possible (face-up vs face down).Primary analyses of short- and longer-term mortality pooled from six trials demonstrated an RR of 0.84 to 0.86 in favour of the prone position (PP), but findings were not statistically significant: In the short term, mortality for those ventilated prone was 33.4% (363/1086) and supine 38.3% (395/1031). This resulted in an RR of 0.84 (95% confidence interval (CI) 0.69 to 1.02) marginally in favour of PP. For longer-term mortality, results showed 41.7% (462/1107) for prone and 47.1% (490/1041) for supine positions, with an RR of 0.86 (95% CI 0.72 to 1.03). The quality of the evidence for both outcomes was rated as low as a result of important potential bias and serious inconsistency.Subgroup analyses for mortality identified three groups consistently favouring PP: those recruited within 48 hours of meeting entry criteria (five trials; 1024 participants showed an RR of 0.75 (95% CI 0.59 to 94)); those treated in the PP for 16 or more hours per day (five trials; 1005 participants showed an RR of 0.77 (95% CI 0.61 to 0.99)); and participants with more severe hypoxaemia at trial entry (six trials; 1108 participants showed an RR of 0.77 (95% CI 0.65 to 0.92)). The quality of the evidence for these outcomes was rated as moderate as a result of potentially important bias.Prone positioning appeared to influence adverse effects: Pressure sores (three trials; 366 participants) with an RR of 1.37 (95% CI 1.05 to 1.79) and tracheal tube obstruction with an RR of 1.78 (95% CI 1.22 to 2.60) were increased with prone ventilation. Reporting of arrhythmias was reduced with PP, with an RR of 0.64 (95% CI 0.47 to 0.87). AUTHORS' CONCLUSIONS: We found no convincing evidence of benefit nor harm from universal application of PP in adults with hypoxaemia mechanically ventilated in intensive care units (ICUs). Three subgroups (early implementation of PP, prolonged adoption of PP and severe hypoxaemia at study entry) suggested that prone positioning may confer a statistically significant mortality advantage. Additional adequately powered studies would be required to confirm or refute these possibilities of subgroup benefit but are unlikely, given results of the most recent study and recommendations derived from several published subgroup analyses. Meta-analysis of individual patient data could be useful for further data exploration in this regard. Complications such as tracheal obstruction are increased with use of prone ventilation. Long-term mortality data (12 months and beyond), as well as functional, neuro-psychological and quality of life data, are required if future studies are to better inform the role of PP in the management of hypoxaemic respiratory failure in the ICU. PMID- 26561746 TI - Can Patient Risk Factors Outperform Antiemetic Guidelines?: Choosing Wisely. PMID- 26561747 TI - The Frequency of Truly Unknown/Undetermined Deaths: A Review of 452 Cases Over a 5-Year Period. AB - The forensic autopsy is often regarded as the final medical diagnosis and expert scientific opinion in matters of death investigation, usually in the legal setting, and sometimes in the clinical setting as well. There are however limitations to what the autopsy can answer, and sometimes the circumstances surrounding a death, despite our best efforts, are simply unable to be determined. Approximately 5% of cases reportedly remain unknown after a complete autopsy. With this in mind, we sought to examine the frequency of deaths in which both the cause and manner are unknown after complete forensic examination and autopsy. Data from 452 undetermined deaths over a 5-year period were analyzed; sudden unexpected infant deaths and decomposed or skeletonized remains were excluded, as well as those with a known cause but undetermined manner of death. After exclusion of these deaths, our analysis revealed that only 0.015% of cases during this period were truly undetermined in both cause and manner of death. PMID- 26561748 TI - Simultaneous sulfate and zinc removal from acid wastewater using an acidophilic and autotrophic biocathode. AB - The aim of this study was to develop microbial electrolysis cell (MEC) with a novel acidophilic and autotrophic biocathode for treatment of acid wastewater. A biocathode was developed using acidophilic sulfate-reducing bacteria as the catalyst. Artificial wastewater with 200mgL(-1) sulfate and different Zn concentrations (0, 15, 25, and 40 mg L(-1)) was used as the MEC catholyte. The acidophilic biocathode dominated by Desulfovibrio sp. with an abundance of 66% (with 82% of Desulfovibrio sequences similar to Desulfovibrio simplex) and achieved a considerable sulfate reductive rate of 32 gm(-3)d(-1). With 15 mg L( 1) Zn added, the sulfate reductive rate of MEC improved by 16%. The formation of ZnS alleviated the inhibition from sulfide and sped the sulfate reduction. With 15 and 25 mgL(-1) Zn added, more than 99% of Zn was removed from the wastewater. Dissolved Zn ions in the catholyte were converted into insoluble Zn compounds, such as zinc sulfide and zinc hydroxide, due to the sulfide and elevated pH produced by sulfate reduction. The MEC with acidophilic and autotrophic biocathode can be used as an alternative to simultaneously remove sulfate and metals from acid wastewaters, such as acid mine drainage. PMID- 26561749 TI - Pilot test of biological removal of 1,4-dioxane from a chemical factory wastewater by gel carrier entrapping Afipia sp. strain D1. AB - A pilot-scale (120 L) bioreactor system using a gel carrier-entrapped pure bacterial strain, Afipia sp. strain D1, capable of degrading 1,4-dioxane as a sole carbon and energy source was constructed and applied to treat real industrial wastewater containing 1,4-dioxane from a chemical factory. Although the wastewater not only contained high concentrations of 1,4-dioxane but also considerable amounts of other organic compounds (73 mg-TOCL(-1) on average), the bioreactor could efficiently remove 1,4-dioxane without significant inhibitory effects. The reactor startup could be completed within approximately 1 month by increasing the 1,4-dioxane loading rate (0.09-0.47 kg-dioxanem(-3)d(-1)) in a stepwise manner. Effective 1,4-dioxane removal was stably maintained for 3 months with an influent 1,4-dioxane of 570-730 mg L(-1), giving an average effluent concentration and removal rate of 3.4 mg L(-1) and 0.46 kg-dioxanem(-3)d(-1), respectively. A 1,4-dioxane loading fluctuation between 0.14 and 0.72 kg dioxanem(-3)d(-1) did not significantly affect its removal, and more than 99% removal efficiency was constantly maintained. The Monod model could well describe the relationship between the effluent 1,4-dioxane concentration and 1,4-dioxane removal rates of the bioreactors, showing that the half-saturation constant (Ks) was 28 mg L(-1). PMID- 26561750 TI - Cerium oxide for the destruction of chemical warfare agents: A comparison of synthetic routes. AB - Four different synthetic routes were used to prepare active forms of cerium oxide that are capable of destroying toxic organophosphates: a sol-gel process (via a citrate precursor), homogeneous hydrolysis and a precipitation/calcination procedure (via carbonate and oxalate precursors). The samples prepared via homogeneous hydrolysis with urea and the samples prepared via precipitation with ammonium bicarbonate (with subsequent calcination at 500 degrees C in both cases) exhibited the highest degradation efficiencies towards the extremely dangerous nerve agents soman (O-pinacolyl methylphosphonofluoridate) and VX (O-ethyl S-[2 (diisopropylamino)ethyl] methylphosphonothioate) and the organophosphate pesticide parathion methyl. These samples were able to destroy more than 90% of the toxic compounds in less than 10 min. The high degradation efficiency of cerium oxide is related to its complex surface chemistry (presence of surface OH groups and surface non-stoichiometry) and to its nanocrystalline nature, which promotes the formation of crystal defects on which the decomposition of organophosphates proceeds through a nucleophilic substitution mechanism that is not dissimilar to the mechanism of enzymatic hydrolysis of organic phosphates by phosphotriesterase. PMID- 26561751 TI - Impact of phosphate on glyphosate uptake and toxicity in willow. AB - Phosphate (PO4(3-)) has been shown to increase glyphosate uptake by willow, a plant species known for its phytoremediation potential. However, it remains unclear if this stimulation of glyphosate uptake can result in an elevated glyphosate toxicity to plants (which could prevent the use of willows in glyphosate-remediation programs). Consequently, we studied the effects of PO4(3-) on glyphosate uptake and toxicity in a fast growing willow cultivar (Salix miyabeana SX64). Plants were grown in hydroponic solution with a combination of glyphosate (0, 0.001, 0.065 and 1 mg l(-1)) and PO4(3-) (0, 200 and 400 mg l( 1)). We demonstrated that PO4(3-) fertilization greatly increased glyphosate uptake by roots and its translocation to leaves, which resulted in increased shikimate concentration in leaves. In addition to its deleterious effects in photosynthesis, glyphosate induced oxidative stress through hydrogen peroxide accumulation. Although it has increased glyphosate accumulation, PO4(3-) fertilization attenuated the herbicide's deleterious effects by increasing the activity of antioxidant systems and alleviating glyphosate-induced oxidative stress. Our results indicate that in addition to the glyphosate uptake, PO4(3-) is involved in glyphosate toxicity in willow by preventing glyphosate induced oxidative stress. PMID- 26561752 TI - Adsorption of nitrate from aqueous solution by magnetic amine-crosslinked biopolymer based corn stalk and its chemical regeneration property. AB - A novel adsorbent of magnetic amine-crosslinked biopolymer based corn stalk (MAB CS) was synthesized and used for nitrate removal from aqueous solution. The characters and adsorption mechanisms of this bio-adsorbent were determined by using VSM, TGA, XRD, SEM, TEM, FT-IR and XPS, respectively. The results revealed that the saturated magnetization of MAB-CS reached 6.25 emu/g. Meanwhile, the studies of various factors indicated that this novel magnetic bio-adsorbent performed well over a considerable wide pH range of 6.0 ~ 9.0, and the presence of PO4(3-) and SO4(2-) would markedly decrease the nitrate removal efficiency. Furthermore, the nitrate adsorption by MAB-CS perfectly fitted the Langmuir isotherm model (R(2)=0.997-0.999) and pseudo second order kinetic model (R(2)=0.953-0.995). The calculated nitrate adsorption capacity of MAB-CS was 102.04 mg/g at 318 K by Langmuir model, and thermodynamic study showed that nitrate adsorption is an spontaneous endothermic process. The regeneration experiments indicated its merit of regeneration and stability with the recovery efficient of 118 ~ 147%. By integrating the experimental results, it was found that the removal of nitrate was mainly via electrostatic attraction and ion exchange. And this novel bio-adsorbent prepared in this work could achieve effective removal of nitrate and rapid separation from effluents simultaneously. PMID- 26561754 TI - The roles of a pillared bentonite on enhancing Se(VI) removal by ZVI and the influence of co-existing solutes in groundwater. AB - The zero-valent iron permeable reactive barrier (ZVI-PRB) is a promising technology for in-situ groundwater remediation. However, its long-term performance often declined due to the blocked reactive sites by corrosion products and by interference of co-existing solutes. In order to address these issues, a pillared bentonite (Al-bent) was homogeneously mixed with ZVI for removing selenate (Se(VI)) from simulated groundwater in column experiments. The Se(VI) removal was enhanced because first Al-bent could facilitate the mass transfer of Se(VI) from solution to iron surface and accelerate Se(VI) reduction. XANES analysis indicated that Se(VI) was almost completely reduced to Se(0) and Se(-II) of less toxicity and solubility by the ZVI/Al-bent mixture, and the buffering effect of Al-bent could maintain the pH at a lower level that favored the Se(VI) removal. Besides, Al-bent could transfer the corrosion products away from iron surface, leading to the enhanced reactivity and longevity of ZVI. The inhibition on reactivity towards Se(VI) in both the single ZVI and the ZVI/Al bent systems increased in the order of Cl(-)AO-H2O2>AO. The biodegradability (BOD5/COD) increased from 0 initially to 0.24, 0.09, and 0.03 for EF, AO-H2O2 and AO processes after 360 min treatment, respectively. Effects of several parameters such as current density, initial pH and Fe(2+) concentration on the EF degradation have also been examined. Three carboxylic acids including oxalic, formic and acetic acid were detected, as well as the released inorganic ions NH4(+), NO3(-) and F(-). At last, an ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry was used to identify about eight aromatic intermediates formed in 60 min of EF treatment, and a plausible mineralization pathway for LEVO by EF treatment was proposed. PMID- 26561757 TI - ACSM Clinician Profile. PMID- 26561758 TI - Updates on Team Rhabdomyolysis, Caffeine Fatalities, and Heat Cramping. PMID- 26561760 TI - Common Tendon Injuries in the Hand. PMID- 26561761 TI - Clinical Utility of Wilson Test for Osteochondral Lesions at the Knee. PMID- 26561762 TI - Bilateral Glenoid Hypoplasia in a College Football Athlete: a Case Report and Review of the Literature. PMID- 26561763 TI - Rapid Weight Loss in Sports with Weight Classes. AB - Weight-sensitive sports are popular among elite and nonelite athletes. Rapid weight loss (RWL) practice has been an essential part of many of these sports for many decades. Due to the limited epidemiological studies on the prevalence of RWL, its true prevalence is unknown. It is estimated that more than half of athletes in weight-class sports have practiced RWL during the competitive periods. As RWL can have significant physical, physiological, and psychological negative effects on athletes, its practice has been discouraged for many years. It seems that appropriate rule changes have had the biggest impact on the practice of RWL in sports like wrestling. An individualized and well-planned gradual and safe weight loss program under the supervision of a team of coaching staff, athletic trainers, sports nutritionists, and sports physicians is recommended. PMID- 26561764 TI - Cross-Country Skiing Injuries and Training Methods. AB - Cross-country skiing is a low injury-risk sport that has many health benefits and few long-term health risks. Some concern exists that cross-country skiing may be associated with a higher incidence of atrial fibrillation; however, mortality rates among skiers are lower than those among the general population. While continuing to emphasize aerobic and anaerobic training, training methods also should promote ski-specific strength training to increase maximum force and its rate of delivery and to build muscular endurance to maintain that power through a race. Multiple tests are available to monitor training progress. Which tests are most appropriate depends on the specific events targeted. In addition to laboratory-based tests, there also are many simpler, more cost-effective tests, such as short time trials, that can be used to monitor training progress and predict performance particularly at the junior skier level where access and cost may be more prohibitive. PMID- 26561765 TI - Athletes Doing Arabesques: Important Considerations in the Care of Young Dancers. AB - Dance is as much a sport as an art form. Sports medicine clinicians seeing dancers in their practice will need to be familiar with the unique characteristics of dance in order to provide proper care. Dance encompasses different forms, which vary in equipment and terminology. The epidemiology of dance injuries has historically focused on ballet, but there is increasing research on other dance forms. Lower extremity and back injuries predominate. Injury prevention, both primary and secondary, is at the heart of dance medicine. Primary prevention includes preseason conditioning, identifying risk factors for injury, and recognizing the female athlete triad. Secondary prevention includes a comprehensive approach to injury rehabilitation, an appreciation for the unique demands of dance, and an understanding of the particulars of the injury being treated. Dancers may have difficulty accessing medical care or following prescribed advice; the proactive clinician will anticipate these situations. PMID- 26561766 TI - Little League Elbow in a Prepubertal Cricket Player. PMID- 26561767 TI - Popliteal Artery Entrapment in a Classical Ballet Dancer: Successful Conservative Management. PMID- 26561768 TI - Heat Illness in Football: Current Concepts. AB - Despite growing health and safety concerns, American football remains a vastly popular sport in the United States. Unfortunately, even with increased efforts in promoting education and hydration, the incidence of death from exertional heat stroke continues to rise. General risk factors such as hydration status, obesity, fitness level, and football-specific risk factors such as timing of training camp and equipment all contribute to the development of heat illness. At the professional level, changes have been made to effectively reduce mortality from heat stroke with no deaths since August 2001. However, there have been at least 33 total deaths at the high school and collegiate levels since this time. More efforts need to be focused at these levels to mandate exertional heat illness prevention guidelines in order to reverse this trend of mortality in our younger athletes. PMID- 26561769 TI - Adhesive systems for restoring primary teeth: a systematic review and meta analysis of in vitro studies. AB - AIM: To systematically review the literature for in vitro studies that evaluated the immediate or after ageing bond strength of etch-and-rinse and self-etch adhesive systems to enamel and dentin of primary teeth. DESIGN: The search was conducted in PubMed/MEDLINE, Cochrane, SciELO, Lilacs, and Scopus databases with no publication year or language limits, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. From 459 potentially eligible studies, 39 were selected for full-text analysis, and 5 were identified in reference lists, with 36 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Pooling bond strength data was calculated using random effects analysis method, comparing two categories of adhesives (etch-and-rinse versus self-etch systems) when applied in different types and conditions of substrate (alpha = 0.05). RESULTS: No statistical significant difference in bond strength between both categories was observed in caries-affected dentin at immediate evaluation and in sound dentin after ageing. Etch-and-rinse adhesives, however, performed better in sound enamel and dentin substrates considering immediate bond strength. None study assessed the long-term adhesive effectiveness to sound or demineralized enamel. CONCLUSION: Although the articles included in this meta analysis showed high heterogeneity and high risk of bias, the in vitro literature suggests superior performance of etch-and-rinse adhesives in primary teeth in comparison with self-etch systems. PMID- 26561770 TI - Eliciting dual-frequency SSVEP using a hybrid SSVEP-P300 BCI. AB - BACKGROUND: Steady-state visual-evoked potential (SSVEP)-based brain-computer interfaces (BCIs) generate weak SSVEP with a monitor and cannot use harmonic frequencies, whereas P300-based BCIs need multiple stimulation sequences. These issues can decrease the information transfer rate (ITR). NEW METHOD: In this paper, we introduce a novel hybrid SSVEP-P300 speller that generates dual frequency SSVEP, allowing it to overcome the abovementioned limitations and improve the performance. The hybrid speller consists of nine panels flickering at different frequencies. Each panel contains four different characters that appear in a random sequence. The flickering panel and the periodically updating character evoke the dual-frequency SSVEP, while the oddball stimulus of the target character evokes the P300. A canonical correlation analysis (CCA) and a step-wise linear discriminant analysis (SWLDA) classified SSVEP and P300, respectively. Ten subjects participated in offline and online experiments, in which accuracy and ITR were compared with those of conventional SSVEP and P300 spellers. RESULTS: The offline analysis revealed not only the P300 potential but also SSVEP with peaks at sub-harmonic frequencies, demonstrating that the proposed speller elicited dual-frequency SSVEP. This dual-frequency stimulation improved SSVEP recognition, increased the number of targets by employing harmonic frequencies, reduced the stimulation time for P300, and consequently improved ITR as compared to the conventional spellers. COMPARISON WITH EXISTING METHODS: The new method reduces the stimulation time and allows harmonic frequencies to be employed for different stimuli. CONCLUSIONS: The results indicate that this study provides a promising approach to make the BCI speller more reliable and efficient. PMID- 26561771 TI - Accurate detection of low signal-to-noise ratio neuronal calcium transient waves using a matched filter. AB - BACKGROUND: Calcium imaging has become a fundamental modality for studying neuronal circuit dynamics both in vitro and in vivo. However, identifying calcium events (CEs) from spectral data remains laborious and difficult, especially since the signal-to-noise ratio (SNR) often falls below 2. Existing automated signal detection methods are generally applied at high SNRs, leaving a large need for an automated algorithm that can accurately extract CEs from fluorescence intensity data of SNR 2 and below. NEW METHOD: In this work we develop a Matched filter for Multi-unit Calcium Event (MMiCE) detection to extract CEs from fluorescence intensity traces of simulated and experimentally recorded neuronal calcium imaging data. RESULTS: MMiCE reached perfect performance on simulated data with SNR >= 2 and a true positive (TP) rate of 98.27% (+/- 1.38% with a 95% confidence interval), and a false positive(FP) rate of 6.59% (+/- 2.56%) on simulated data with SNR 0.2. On real data, verified by patch-clamp recording, MMiCE performed with a TP rate of 100.00% (+/- 0.00) and a FP rate of 2.04% (+/- 4.10). COMPARISON WITH EXISTING METHOD(S): This high level of performance exceeds existing methods at SNRs as low as 0.2, which are well below those used in previous studies (SNR ? 5-10). CONCLUSION: Overall, the MMiCE detector performed exceptionally well on both simulated data, and experimentally recorded neuronal calcium imaging data. The MMiCE detector is accurate, reliable, well suited for wide-spread use, and freely available at sites.uci.edu/aggies or from the corresponding author. PMID- 26561772 TI - A regression method for estimating performance in a rapid serial visual presentation target detection task. AB - BACKGROUND: Estimating target detection performance in the rapid serial visual presentation (RSVP) target detection paradigm can be challenging when the inter stimulus interval is small relative to the variability in human response time. The challenge arises because assigning a particular response to the correct image cannot be done with certainty. Existing solutions to this challenge establish a heuristic for assigning responses to images and thereby determining which responses are hits and which are false alarms. NEW METHOD: We developed a regression-based method for estimating hit rate and false alarm rate that corrects for expected errors in a likelihood-based assignment of responses to stimuli. RESULTS: Simulations show that this regression method results in an unbiased and accurate estimate of target detection performance. COMPARISON WITH EXISTING METHODS: The regression method had lower estimation error compared to three existing methods, and in contrast to the existing methods, the errors made by the regression method do not depend strongly on the true values of hit rate and false alarm rate. The most commonly used existing method performed well when simulated performance was nearly perfect, but not when behavioral error rates increased. CONCLUSIONS: Based on its better estimation of hit rate and false alarm rate, the regression method proposed here would seem the best choice when estimating the hit rate and false alarm rate is the primary interest. PMID- 26561773 TI - Ecabet sodium alleviates neomycin-induced hair cell damage. AB - Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 MUg/mL for 1 h, followed by 125 MUM neomycin for 1h. The positive control group was established by 125 MUM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 MUM/ml ES treatment (12.98 +/- 2.59 cells) comparing to that of the negative control group (14.15 +/- 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 +/- 0.91 cells, p < 0.01). The production of reactive oxygen species significantly increased by 183% with 125 MUM neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 MUM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p < 0.01) and a significantly increased DASPEI reactivity (reflecting viable mitochondria, p < 0.01) were observed in 40 MUM/ml ES pre treatment group. Our data suggest that ES could protect against neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation. PMID- 26561774 TI - A reaction-diffusion model of cytosolic hydrogen peroxide. AB - As a signaling molecule in mammalian cells, hydrogen peroxide (H2O2) determines the thiol/disulfide oxidation state of several key proteins in the cytosol. Localization is a key concept in redox signaling; the concentrations of signaling molecules within the cell are expected to vary in time and in space in manner that is essential for function. However, as a simplification, all theoretical studies of intracellular hydrogen peroxide and many experimental studies to date have treated the cytosol as a well-mixed compartment. In this work, we incorporate our previously reported reduced kinetic model of the network of reactions that metabolize hydrogen peroxide in the cytosol into a model that explicitly treats diffusion along with reaction. We modeled a bolus addition experiment, solved the model analytically, and used the resulting equations to quantify the spatiotemporal variations in intracellular H2O2 that result from this kind of perturbation to the extracellular H2O2 concentration. We predict that micromolar bolus additions of H2O2 to suspensions of HeLa cells (0.8 * 10(9)cells/l) result in increases in the intracellular concentration that are localized near the membrane. These findings challenge the assumption that intracellular concentrations of H2O2 are increased uniformly throughout the cell during bolus addition experiments and provide a theoretical basis for differing phenotypic responses of cells to intracellular versus extracellular perturbations to H2O2 levels. PMID- 26561775 TI - Glutathione-S-transferase omega 1 (GSTO1-1) acts as mediator of signaling pathways involved in aflatoxin B1-induced apoptosis-autophagy crosstalk in macrophages. AB - Aflatoxin B1 (AFB1) is the most toxic aflatoxin species and has been shown to be associated with specific as well as non-specific immune responses. In the present study, using murine macrophage Raw 264.7 cells as a model, we report that short exposure (6h) to AFB1 caused an increase in the cellular calcium pool in mitochondria, which in turn elevated reactive oxygen species (ROS)-mediated oxidative stress and led to loss of mitochondrial membrane potential and ultimately c-Jun N-terminal kinases (JNK)-mediated caspase-dependent cell death. On the contrary, longer exposure (12h) to AFB1 reduced JNK phosphorylation and cell death in macrophages. Measurement of autophagic flux demonstrated that autophagy induction through the canonical pathway was responsible for suppressing AFB1-induced apoptosis after 12h. As a detailed molecular mechanism, we found that the unfolded protein response (UPR) machinery was active at 12h post exposure to AFB1 and induced cytoprotective autophagy as confirmed by determination of major autophagic markers. Inhibition of autophagy by Beclin-1 siRNA also resulted in JNK-mediated cell death. We further established that glutathione S transferase omega1-1 (GSTO1-1), a specific class of GST, was the responsible factor between apoptosis and autophagy crosstalk. Targeting of GSTO1 1 increased JNK-mediated apoptosis by 2-fold compared to the control, whereas autophagy rate was reduced. Thus, increased expression of GSTO1-1 was associated with increased protein glutathionylation, an important protein modification in response to cellular redox status. PMID- 26561776 TI - Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins. AB - Phosphatase and tensin homolog (PTEN) is involved in a number of different cellular processes including metabolism, apoptosis, cell proliferation and survival. It is a redox-sensitive dual-specificity protein phosphatase that acts as a tumor suppressor by negatively regulating the PI3K/Akt pathway. While direct evidence of redox regulation of PTEN downstream signaling has been reported, the effect of PTEN redox status on its protein-protein interactions is poorly understood. PTEN-GST in its reduced and a DTT-reversible H2O2-oxidized form was immobilized on a glutathione-sepharose support and incubated with cell lysate to capture interacting proteins. Captured proteins were analyzed by LC-MSMS and comparatively quantified using label-free methods. 97 Potential protein interactors were identified, including a significant number that are novel. The abundance of fourteen interactors was found to vary significantly with the redox status of PTEN. Altered binding to PTEN was confirmed by affinity pull-down and Western blotting for Prdx1, Trx, and Anxa2, while DDB1 was validated as a novel interactor with unaltered binding. These results suggest that the redox status of PTEN causes a functional variation in the PTEN interactome. The resin capture method developed had distinct advantages in that the redox status of PTEN could be directly controlled and measured. PMID- 26561777 TI - The metabolic network of Clostridium acetobutylicum: Comparison of the approximate Bayesian computation via sequential Monte Carlo (ABC-SMC) and profile likelihood estimation (PLE) methods for determinability analysis. AB - The Gram-positive bacterium Clostridium acetobutylicum is an anaerobic endospore forming species which produces acetone, butanol and ethanol via the acetone butanol (AB) fermentation process, leading to biofuels including butanol. In previous work we looked to estimate the parameters in an ordinary differential equation model of the glucose metabolism network using data from pH-controlled continuous culture experiments. Here we combine two approaches, namely the approximate Bayesian computation via an existing sequential Monte Carlo (ABC-SMC) method (to compute credible intervals for the parameters), and the profile likelihood estimation (PLE) (to improve the calculation of confidence intervals for the same parameters), the parameters in both cases being derived from experimental data from forward shift experiments. We also apply the ABC-SMC method to investigate which of the models introduced previously (one non sporulation and four sporulation models) have the greatest strength of evidence. We find that the joint approximate posterior distribution of the parameters determines the same parameters as previously, including all of the basal and increased enzyme production rates and enzyme reaction activity parameters, as well as the Michaelis-Menten kinetic parameters for glucose ingestion, while other parameters are not as well-determined, particularly those connected with the internal metabolites acetyl-CoA, acetoacetyl-CoA and butyryl-CoA. We also find that the approximate posterior is strongly non-Gaussian, indicating that our previous assumption of elliptical contours of the distribution is not valid, which has the effect of reducing the numbers of pairs of parameters that are (linearly) correlated with each other. Calculations of confidence intervals using the PLE method back this up. Finally, we find that all five of our models are equally likely, given the data available at present. PMID- 26561778 TI - A simple approximation of moments of the quasi-equilibrium distribution of an extended stochastic theta-logistic model with non-integer powers. AB - The stochastic versions of the logistic and extended logistic growth models are applied successfully to explain many real-life population dynamics and share a central body of literature in stochastic modeling of ecological systems. To understand the randomness in the population dynamics of the underlying processes completely, it is important to have a clear idea about the quasi-equilibrium distribution and its moments. Bartlett et al. (1960) took a pioneering attempt for estimating the moments of the quasi-equilibrium distribution of the stochastic logistic model. Matis and Kiffe (1996) obtain a set of more accurate and elegant approximations for the mean, variance and skewness of the quasi equilibrium distribution of the same model using cumulant truncation method. The method is extended for stochastic power law logistic family by the same and several other authors (Nasell, 2003; Singh and Hespanha, 2007). Cumulant truncation and some alternative methods e.g. saddle point approximation, derivative matching approach can be applied if the powers involved in the extended logistic set up are integers, although plenty of evidence is available for non-integer powers in many practical situations (Sibly et al., 2005). In this paper, we develop a set of new approximations for mean, variance and skewness of the quasi-equilibrium distribution under more general family of growth curves, which is applicable for both integer and non-integer powers. The deterministic counterpart of this family of models captures both monotonic and non-monotonic behavior of the per capita growth rate, of which theta-logistic is a special case. The approximations accurately estimate the first three order moments of the quasi-equilibrium distribution. The proposed method is illustrated with simulated data and real data from global population dynamics database. PMID- 26561780 TI - Frequency and cause of readmissions following pediatric otolaryngologic surgery. AB - OBJECTIVES/HYPOTHESIS: To characterize the frequency and nature of readmissions to free standing pediatric hospitals after otolaryngologic procedures. STUDY DESIGN: Retrospective national database analysis. METHODS: Using the Pediatric Health Information Systems database, we examined 30-day inpatient readmissions in children less than 18 years old who underwent otolaryngology procedures between January 1, 2009, and December 31, 2011. Univariate and multivariate logistic regression analyses accounting for correlated structure of the data identified factors related to readmission rate. Reasons for readmission and the postoperative day at which readmission occurred were also examined. RESULTS: In the 24-month study period, a total of 493,507 procedures were performed, resulting in 11,574 (2.3%) 30-day readmissions. Readmission rates varied significantly based on the type of procedure, patient age, and presence of chronic medical condition(s). Direct surgical complications accounted for 3,432 (29.7%) of all readmissions; and 4,729 (40.9%) of all readmissions occurred following tonsil and adenoid surgery. CONCLUSION: Readmissions after pediatric otolaryngologic surgery are relatively uncommon. These readmission rates vary directly with the type of procedure performed, as well as patient level factors (i.e., patient age, ethnicity, and the presence of other medical comorbidities). These data demonstrate that if readmission rates are to be used as a quality measure in pediatric otolaryngology procedures, complex risk adjustment of patient level variables will be necessary to accurately compare outcomes between different hospitals. PMID- 26561779 TI - The enteric microbiome in hepatobiliary health and disease. AB - Increasing evidence points to the contribution of the intestinal microbiome as a potentially key determinant in the initiation and/or progression of hepatobiliary disease. While current understanding of this dynamic is incomplete, exciting insights are continually being made and more are expected given the developments in molecular and high-throughput omics techniques. In this brief review, we provide a practical and updated synopsis of the interaction of the intestinal microbiome with the liver and its downstream impact on the initiation, progression and complications of hepatobiliary disease. PMID- 26561781 TI - Helicobacter pylori VacA toxin causes cell death by inducing accumulation of cytoplasmic connexin 43. PMID- 26561782 TI - Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration- and time-dependent manner. Within 15 min after the treatment of RPE with 25 MUM A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL)1beta, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1beta, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the secretion of inflammatory cytokines and VEGFA. PMID- 26561783 TI - Differentiation of human neuroblastoma cells toward the osteogenic lineage by mTOR inhibitor. AB - Current hypothesis suggest that tumors can originate from adult cells after a process of 'reprogramming' driven by genetic and epigenetic alterations. These cancer cells, called cancer stem cells (CSCs), are responsible for the tumor growth and metastases. To date, the research effort has been directed to the identification, isolation and manipulation of this cell population. Independently of whether tumors were triggered by a reprogramming of gene expression or seeded by stem cells, their energetic metabolism is altered compared with a normal cell, resulting in a high aerobic glycolytic 'Warburg' phenotype and dysregulation of mitochondrial activity. This metabolic alteration is intricately linked to cancer progression.The aim of this work has been to demonstrate the possibility of differentiating a neoplastic cell toward different germ layer lineages, by evaluating the morphological, metabolic and functional changes occurring in this process. The cellular differentiation reported in this study brings to different conclusions from those present in the current literature. We demonstrate that 'in vitro' neuroblastoma cancer cells (chosen as experimental model) are able to differentiate directly into osteoblastic (by rapamycin, an mTOR inhibitor) and hepatic lineage without an intermediate 'stem' cell step. This process seems owing to a synergy among few master molecules, metabolic changes and scaffold presence acting in a concerted way to control the cell fate. PMID- 26561786 TI - Erratum: Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering. PMID- 26561784 TI - Dietary Supplementation with Specific Collagen Peptides Has a Body Mass Index Dependent Beneficial Effect on Cellulite Morphology. AB - In this double-blind, placebo-controlled clinical study, we investigated the efficacy of specific bioactive collagen peptides (BCP) on the cellulite treatment of normal and overweight women. In total, 105 women aged 24-50 years with moderate cellulite were randomized to orally receive a daily dosage of 2.5 g BCP or a placebo over 6 months. The degree of cellulite was evaluated before starting the treatment and after 3 and 6 months of intake. In addition, skin waviness, dermal density, and the length of subcutaneous borderline were assessed. BCP treatment led to a statistically significant decrease in the degree of cellulite and a reduced skin waviness on thighs (P < 0.05) in normal weight women. Moreover, dermal density was significantly improved (P < 0.05) compared to placebo. The subcutaneous borderline showed a significant shortening after BCP intake compared to the beginning of the study, indicating cellulite improvement, but the data failed to reach statistical significance compared to placebo. The efficacy of BCP treatment was also confirmed in overweight women, although the impact was less pronounced in comparison with women of normal body weight. The results of the study demonstrated that a regular ingestion of BCP over a period of 6 months led to a clear improvement of the skin appearance in women suffering from moderate cellulite. Based on the current data, it can be concluded that a long-term therapy with orally administered BCP leads to an improvement of cellulite and has a positive impact on skin health. PMID- 26561785 TI - Simultaneous Site-Specific Dual Protein Labeling Using Protein Prenyltransferases. AB - Site-specific protein labeling is an important technique in protein chemistry and is used for diverse applications ranging from creating protein conjugates to protein immobilization. Enzymatic reactions, including protein prenylation, have been widely exploited as methods to accomplish site-specific labeling. Enzymatic prenylation is catalyzed by prenyltransferases, including protein farnesyltransferase (PFTase) and geranylgeranyltransferase type I (GGTase-I), both of which recognize C-terminal CaaX motifs with different specificities and transfer prenyl groups from isoprenoid diphosphates to their respective target proteins. A number of isoprenoid analogues containing bioorthogonal functional groups have been used to label proteins of interest via PFTase-catalyzed reaction. In this study, we sought to expand the scope of prenyltransferase mediated protein labeling by exploring the utility of rat GGTase-I (rGGTase-I). First, the isoprenoid specificity of rGGTase-I was evaluated by screening eight different analogues and it was found that those with bulky moieties and longer backbone length were recognized by rGGTase-I more efficiently. Taking advantage of the different substrate specificities of rat PFTase (rPFTase) and rGGTase-I, we then developed a simultaneous dual labeling method to selectively label two different proteins by using isoprenoid analogue and CaaX substrate pairs that were specific to only one of the prenyltransferases. Using two model proteins, green fluorescent protein with a C-terminal CVLL sequence (GFP-CVLL) and red fluorescent protein with a C-terminal CVIA sequence (RFP-CVIA), we demonstrated that when incubated together with both prenyltransferases and the selected isoprenoid analogues, GFP-CVLL was specifically modified with a ketone functionalized analogue by rGGTase-I and RFP-CVIA was selectively labeled with an alkyne-containing analogue by rPFTase. By switching the ketone-containing analogue to an azide-containing analogue, it was possible to create protein tail to-tail dimers in a one-pot procedure through the copper(I)-catalyzed alkyne azide cycloaddition (CuAAC) reaction. Overall, with the flexibility of using different isoprenoid analogues, this system greatly extends the utility of protein labeling using prenyltransferases. PMID- 26561787 TI - Comparison between gold nanoparticle and gold plane electron emissions: a way to identify secondary electron emission. AB - To understand the nanoparticle radiosensitising effect observed in the radiotherapy context, it is necessary to study the nanoparticle electron emission under x-ray irradiation, which is one of the causes of the radiosensitisation. In this paper, we compare the electron energy spectrum of gold samples irradiated by 1253.6 eV x-ray photons for energies down to 2 eV for nanoparticles and for a plane surface. This comparison highlights important differences due to nanoparticle properties especially at low energy, allowing the identification of strong nanoparticle secondary electron emission. This strong nanoparticle emission could play a very important role in radiosensitisation mechanisms. PMID- 26561788 TI - A Highly Stereoselective, Efficient, and Scalable Synthesis of the C(1)-C(9) Fragment of the Epothilones. AB - A second-generation synthesis of the C(1)-C(9) fragment of the epothilones is reported. The key tandem intramolecular silylformylation/crotylsilylation/"aprotic" Tamao oxidation sequence has been redeveloped as a stepwise intermolecular variant, allowing excellent levels of diastereoselectivity in the crotylation step and proceeds in 50% overall yield on gram scale. An improved synthesis of the homopropargyl alcohol starting material is also described, which proceeds in four steps and >99% ee from inexpensive starting materials and is amenable to multigram scales. PMID- 26561789 TI - Campylobacter species isolated from poultry and humans, and their analysis using PFGE in southern Brazil. AB - Campylobacteriosis is a bacterial disease transmitted to humans through ingestion of contaminated food. Six hundred samples were collected, 200 from human stool samples, 200 from poultry products and 200 from poultry feces in Southern Brazil, and then inoculated on blood agar plates. A total of 58% of the poultry feces, 17% of the poultry meat, and 2% the of human stools tested positive for Campylobacter. Positive Campylobacter colonies were identified as Campylobacter jejuni or Campylobactercoli by multiplex PCR. Campylobacter isolates were analyzed using PFGE to compare different profiles according to the source. This study demonstrated that there are different Campylobacter clones distributed in different aviaries in Southern Brazil. In addition, PFGE molecular profiles suggested that broilers can be a source of contamination of poultry products. However, the human isolate studied did not show any relationship with other strains examined. PMID- 26561790 TI - Causes of neuropathy in patients referred as "idiopathic neuropathy". AB - INTRODUCTION: The etiology of neuropathy was idiopathic in 20%-30% of patients despite thorough investigation, based on results from the 1980s and 1990s. Since then, new etiologies have been recognized, and skin biopsy has been used to confirm small-fiber neuropathy. METHODS: The authors reviewed the charts of 373 patients with idiopathic neuropathy who were referred to a neuropathy center between 2002 and 2012. RESULTS: Among the 284 eligible patients, 93 (32.7%) remained idiopathic. The most common cause was impaired glucose metabolism (72 patients, 25.3%), including diabetes in 26 and prediabetes in 46. Other etiologies were chronic inflammatory demyelinating polyneuropathy (CIDP) in 57 (20%) and monoclonal gammopathy in 20 (7%), as well as toxic, Sjogren disease, celiac disease, other immune-mediated diseases, vitamin B12 deficiency, amyloidosis, vitamin B1 and B6 deficiency, vasculitis, hypothyroidism, hereditary, Lyme disease, and anti-sulfatide antibody. CONCLUSIONS: The major causes of undiagnosed neuropathies were impaired glucose metabolism, CIDP, and monoclonal gammopathies. Despite thorough evaluation 32.7% remained idiopathic. Muscle Nerve 53: 856-861, 2016. PMID- 26561791 TI - Student Veteran perceptions of facilitators and barriers to achieving academic goals. AB - According to recent estimates, over 1 million Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans are utilizing the post-9/11 GI Bill to pursue higher education. Data collected by the Department of Defense suggests that greater than 17% of returning Veterans may suffer from mental and physical health disorders, which can negatively affect school performance. The current study explored student Veterans' perceived facilitators and barriers to achieving academic goals. Thirty-one student Veterans completed self-report measures and interviews. Results suggested that Veterans that were reporting problems or symptoms in one mental or physical health domain were likely to be reporting symptoms or problems in others as well. The interview data were coded, and three overarching themes related to barriers and facilitators emerged: person features (e.g., discipline and determination, symptoms and stressors), institutional structure (i.e., what schools and the Department of Veterans Affairs do that was perceived to help or hinder student Veteran success), and policy concerns (i.e., how the structure of the GI Bill affects student Veteran school experience). Results from this research indicate the need for larger studies and program development efforts aimed at enhancing academic outcomes for Veterans. PMID- 26561793 TI - Purification and Partial Characterization of beta-Glucosidase in Chayote (Sechium edule). AB - beta-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this beta-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. beta-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other beta glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus beta glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of beta-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred MUg/mL beta-D-glucose inhibited beta-glucosidase activity by more than 50%. The enzyme had a Km of 4.88 mM with p-NPG and a Kcat of 10,000 min(-1). The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 degrees C. PMID- 26561794 TI - Antihypertensive Effects of Artemisia scoparia Waldst in Spontaneously Hypertensive Rats and Identification of Angiotensin I Converting Enzyme Inhibitors. AB - We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4'-O-beta-D glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data. PMID- 26561795 TI - Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs. AB - Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 MUm, 2.1*50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2-200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within +/-12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 ug/L, and the AUC values were 606.7, 419.1 and 236.2 ug/L.h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations. PMID- 26561796 TI - Synthesis and Chemistry of Organic Geminal Di- and Triazides. AB - This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections. PMID- 26561798 TI - Synergy and Other Interactions between Polymethoxyflavones from Citrus Byproducts. AB - The citrus by-products released from citrus processing plants may contain high levels of potentially bioactive compounds such as flavonoids, which are a widely distributed group of polyphenolic compounds with health-related properties based on their antioxidant activity. In the study reported here, the potential bioactivities and antioxidant activities of extracts, fractions and compounds from citrus by-products were evaluated along with the chemical interactions of binary mixtures of compounds and complex mixtures. The bioactivities and interactions were evaluated in wheat coleoptile bioassays and the antioxidant activity was evaluated by the al DPPH (2,2-diphenyl-1-picrylhdrazyl radical) radical scavenging assay. The extracts, fractions and most of the isolated compounds (mainly polymethoxyflavones) showed high activity in the wheat coleoptile bioassay. However, the antioxidant activity was not consistently high, except in the acetone extract fractions. Moreover, a study of the interactions with binary mixtures of polymethoxyflavones showed the occurrence of synergistic effects. The complex mixtures of fractions composed mainly of polymethoxyflavones caused a synergistic effect when it was added to a bioactive compound such as anethole. The results reported here highlight a new application for the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in compounds or mixtures. PMID- 26561797 TI - Design, Synthesis and in Vivo Evaluation of Novel Glycosylated Sulfonylureas as Antihyperglycemic Agents. AB - Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the introduction of the glucosamine moiety is to enhance selective drug uptake by pancreatic beta-cells in order to decrease the cardiotoxic side effect commonly associated with sulfonylurea agents. 2-Deoxy-2 (4-chlorophenylsulfonylurea)-D-glucopyranose was found to be the most potent antihyperglycaemic agents among the synthesized compounds in diabetic mice. This investigation indicates the importance of this novel class as potential antihyperglycaemic agents. PMID- 26561799 TI - Constituents and Pharmacological Activities of Myrcia (Myrtaceae): A Review of an Aromatic and Medicinal Group of Plants. AB - Myrcia is one of the largest genera of the economically important family Myrtaceae. Some of the species are used in folk medicine, such as a group known as "pedra-hume-caa" or "pedra-ume-caa" or "insulina vegetal" (insulin plant) that it is used for the treatment of diabetes. The species are an important source of essential oils, and most of the chemical studies on Myrcia describe the chemical composition of the essential oils, in which mono- and sesquiterpenes are predominant. The non-volatile compounds isolated from Myrcia are usually flavonoids, tannins, acetophenone derivatives and triterpenes. Anti-inflammatory, antinociceptive, antioxidant, antimicrobial activities have been described to Myrcia essential oils, while hypoglycemic, anti-hemorrhagic and antioxidant activities were attributed to the extracts. Flavonoid glucosides and acetophenone derivatives showed aldose reductase and alpha-glucosidase inhibition, and could explain the traditional use of Myrcia species to treat diabetes. Antimicrobial and anti-inflammatory are some of the activities observed for other isolated compounds from Myrcia. PMID- 26561800 TI - Connexin 50 Expression in Ependymal Stem Progenitor Cells after Spinal Cord Injury Activation. AB - Ion channels included in the family of Connexins (Cx) help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50) in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC). epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI) (epSPCi). When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi. PMID- 26561801 TI - Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy- Long-Term Outcome of a Phase II Pilot Study. AB - Hilar cholangiocarcinoma (CC) is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0) recurrence can be as high as 70%. Photodynamic therapy (PDT) is an established palliative local tumor ablative treatment for non resectable hilar CC. We report the long-term outcome of curative resection (R0) performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years) with initially non-resectable hilar CC. Photofrin((r)) was injected intravenously 24-48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0) resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments--however, this concept needs to be validated in a larger trial. PMID- 26561803 TI - Plant Responses to Nanoparticle Stress. AB - With the rapid advancement in nanotechnology, release of nanoscale materials into the environment is inevitable. Such contamination may negatively influence the functioning of the ecosystems. Many manufactured nanoparticles (NPs) contain heavy metals, which can cause soil and water contamination. Proteomic techniques have contributed substantially in understanding the molecular mechanisms of plant responses against various stresses by providing a link between gene expression and cell metabolism. As the coding regions of genome are responsible for plant adaptation to adverse conditions, protein signatures provide insights into the phytotoxicity of NPs at proteome level. This review summarizes the recent contributions of plant proteomic research to elaborate the complex molecular pathways of plant response to NPs stress. PMID- 26561802 TI - The Role of Autophagy in Hepatocellular Carcinoma. AB - Autophagy is a catabolic process involved in cellular homeostasis under basal and stressed conditions. Autophagy is crucial for normal liver physiology and the pathogenesis of liver diseases. During the last decade, the function of autophagy in hepatocellular carcinoma (HCC) has been evaluated extensively. Currently, autophagy is thought to play a dual role in HCC, i.e., autophagy is involved in tumorigenesis and tumor suppression. Recent investigations of autophagy have suggested that autophagy biomarkers can facilitate HCC prognosis and the establishment of therapeutic approaches. In this review, we briefly summarize the current understanding of autophagy and discuss recent evidence for its role in HCC. PMID- 26561804 TI - Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model. AB - Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-gamma, TNF-alpha, IL-12, IL-6, and IL-1beta in mice with TNBS induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-gamma, TNF-alpha, IL-12, IL-6, and IL-1beta were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells. PMID- 26561806 TI - The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis. AB - Peripheral blood lymphocytes are an attractive tool because there is accumulating evidence indicating that lymphocytes may be utilized as a biomarker in the field of psychiatric study as they could reveal the condition of cells distributed in the brain. Here, we measured the mRNA expression status of dopamine receptor D2 (DRD2), DRD3, and dopamine and cyclic adenosine 3',5'-monophosphate regulated phosphoprotein-32 (DARPP-32) in T lymphocytes of patients with early psychosis by quantitative real-time polymerase chain reaction (q-PCR) and explored the relationships between their mRNA levels and the psychopathological status of patients. The present study demonstrated that the mRNA expression levels of DRD3 in T lymphocytes were significantly different among controls, and in patients with psychotic disorder not otherwise specified (NOS) and schizophrenia/schizophreniform disorder. However, no significant differences in mRNA expression levels of DRD2 and DARPP-32 were found among the three groups. We found a significant positive correlation between the DRD2 mRNA level and the score of the excited factor of the Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia/schizophreniform disorder. These findings suggest that DRD3 mRNA levels may serve as a potential diagnostic biomarker differentiating patients with early psychosis from controls. PMID- 26561805 TI - Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced Pluripotent Stem Cells. AB - Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies. PMID- 26561807 TI - Low T3 State Is Correlated with Cardiac Mitochondrial Impairments after Ischemia Reperfusion Injury: Evidence from a Proteomic Approach. AB - Mitochondria are major determinants of cell fate in ischemia/reperfusion injury (IR) and common effectors of cardio-protective strategies in cardiac ischemic disease. Thyroid hormone homeostasis critically affects mitochondrial function and energy production. Since a low T3 state (LT3S) is frequently observed in the post infarction setting, the study was aimed to investigate the relationship between 72 h post IR T3 levels and both the cardiac function and the mitochondrial proteome in a rat model of IR. The low T3 group exhibits the most compromised cardiac performance along with the worst mitochondrial activity. Accordingly, our results show a different remodeling of the mitochondrial proteome in the presence or absence of a LT3S, with alterations in groups of proteins that play a key role in energy metabolism, quality control and regulation of cell death pathways. Overall, our findings highlight a relationship between LT3S in the early post IR and poor cardiac and mitochondrial outcomes, and suggest a potential implication of thyroid hormone in the cardio-protection and tissue remodeling in ischemic disease. PMID- 26561809 TI - Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia--A Case of Novel Weapons? AB - Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant's capacity to deter natural enemies in its invaded range through production of novel weapons. PMID- 26561808 TI - Contribution of the Type II Chaperonin, TRiC/CCT, to Oncogenesis. AB - The folding of newly synthesized proteins and the maintenance of pre-existing proteins are essential in sustaining a living cell. A network of molecular chaperones tightly guides the folding, intracellular localization, and proteolytic turnover of proteins. Many of the key regulators of cell growth and differentiation have been identified as clients of molecular chaperones, which implies that chaperones are potential mediators of oncogenesis. In this review, we briefly provide an overview of the role of chaperones, including HSP70 and HSP90, in cancer. We further summarize and highlight the emerging the role of chaperonin TRiC (T-complex protein-1 ring complex, also known as CCT) in the development and progression of cancer mediated through its critical interactions with oncogenic clients that modulate growth deregulation, apoptosis, and genome instability in cancer cells. Elucidation of how TRiC modulates the folding and function of oncogenic clients will provide strategies for developing novel cancer therapies. PMID- 26561810 TI - The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model. AB - This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiography, micro-computed tomography (CT), and histological examination. In vitro studies included the surface morphology of BCP and Aln-loaded BCP scaffolds visualized using field-emission scanning electron microscope, release kinetics of Aln from BCP scaffolds, alkaline phosphatase (ALP) activity, calcium deposition, and gene expression. The in vitro studies showed that sustained release of Aln from the BCP scaffolds consisted of porous microstructures, and revealed that MG 63 cells cultured on Aln-loaded BCP scaffolds showed significantly increased ALP activity, calcium deposition, and gene expression compared to cells cultured on BCP scaffolds. The in vivo studies using radiograph and histology examination revealed abundant callus formation and bone maturation at the site in the Aln/BCP groups compared to the control group. However, solid bony bridge formation was not observed at plain radiographs until 8 weeks. Micro-CT analysis revealed that bone mineral density and bone formation volume were increased over time in an Aln concentration-dependent manner. These results suggested that Aln/BCP scaffolds have the potential for controlling the release of Aln and enhance bone formation and mineralization. PMID- 26561811 TI - Smartphone Application for the Analysis of Prosodic Features in Running Speech with a Focus on Bipolar Disorders: System Performance Evaluation and Case Study. AB - Bipolar disorder is one of the most common mood disorders characterized by large and invalidating mood swings. Several projects focus on the development of decision support systems that monitor and advise patients, as well as clinicians. Voice monitoring and speech signal analysis can be exploited to reach this goal. In this study, an Android application was designed for analyzing running speech using a smartphone device. The application can record audio samples and estimate speech fundamental frequency, F0, and its changes. F0-related features are estimated locally on the smartphone, with some advantages with respect to remote processing approaches in terms of privacy protection and reduced upload costs. The raw features can be sent to a central server and further processed. The quality of the audio recordings, algorithm reliability and performance of the overall system were evaluated in terms of voiced segment detection and features estimation. The results demonstrate that mean F0 from each voiced segment can be reliably estimated, thus describing prosodic features across the speech sample. Instead, features related to F0 variability within each voiced segment performed poorly. A case study performed on a bipolar patient is presented. PMID- 26561812 TI - Quantitative Ethylene Measurements with MOx Chemiresistive Sensors at Different Relative Air Humidities. AB - The sensitivity of two commercial metal oxide (MOx) sensors to ethylene is tested at different relative humidities. One sensor (MiCS-5914) is based on tungsten oxide, the other (MQ-3) on tin oxide. Both sensors were found to be sensitive to ethylene concentrations down to 10 ppm. Both sensors have significant response times; however, the tungsten sensor is the faster one. Sensor models are developed that predict the concentration of ethylene given the sensor output and the relative humidity. The MQ-3 sensor model achieves an accuracy of +/-9.2 ppm and the MiCS-5914 sensor model predicts concentration to +/-7.0 ppm. Both sensors are more accurate for concentrations below 50 ppm, achieving +/-6.7 ppm (MQ-3) and 5.7 ppm (MiCS-5914). PMID- 26561813 TI - A Review of LIDAR Radiometric Processing: From Ad Hoc Intensity Correction to Rigorous Radiometric Calibration. AB - In addition to precise 3D coordinates, most light detection and ranging (LIDAR) systems also record "intensity", loosely defined as the strength of the backscattered echo for each measured point. To date, LIDAR intensity data have proven beneficial in a wide range of applications because they are related to surface parameters, such as reflectance. While numerous procedures have been introduced in the scientific literature, and even commercial software, to enhance the utility of intensity data through a variety of "normalization", "correction", or "calibration" techniques, the current situation is complicated by a lack of standardization, as well as confusing, inconsistent use of terminology. In this paper, we first provide an overview of basic principles of LIDAR intensity measurements and applications utilizing intensity information from terrestrial, airborne topographic, and airborne bathymetric LIDAR. Next, we review effective parameters on intensity measurements, basic theory, and current intensity processing methods. We define terminology adopted from the most commonly-used conventions based on a review of current literature. Finally, we identify topics in need of further research. Ultimately, the presented information helps lay the foundation for future standards and specifications for LIDAR radiometric calibration. PMID- 26561814 TI - Kinematic Model-Based Pedestrian Dead Reckoning for Heading Correction and Lower Body Motion Tracking. AB - In this paper, we present a method for finding the enhanced heading and position of pedestrians by fusing the Zero velocity UPdaTe (ZUPT)-based pedestrian dead reckoning (PDR) and the kinematic constraints of the lower human body. ZUPT is a well known algorithm for PDR, and provides a sufficiently accurate position solution for short term periods, but it cannot guarantee a stable and reliable heading because it suffers from magnetic disturbance in determining heading angles, which degrades the overall position accuracy as time passes. The basic idea of the proposed algorithm is integrating the left and right foot positions obtained by ZUPTs with the heading and position information from an IMU mounted on the waist. To integrate this information, a kinematic model of the lower human body, which is calculated by using orientation sensors mounted on both thighs and calves, is adopted. We note that the position of the left and right feet cannot be apart because of the kinematic constraints of the body, so the kinematic model generates new measurements for the waist position. The Extended Kalman Filter (EKF) on the waist data that estimates and corrects error states uses these measurements and magnetic heading measurements, which enhances the heading accuracy. The updated position information is fed into the foot mounted sensors, and reupdate processes are performed to correct the position error of each foot. The proposed update-reupdate technique consequently ensures improved observability of error states and position accuracy. Moreover, the proposed method provides all the information about the lower human body, so that it can be applied more effectively to motion tracking. The effectiveness of the proposed algorithm is verified via experimental results, which show that a 1.25% Return Position Error (RPE) with respect to walking distance is achieved. PMID- 26561815 TI - Frequency-Switchable Metamaterial Absorber Injecting Eutectic Gallium-Indium (EGaIn) Liquid Metal Alloy. AB - In this study, we demonstrated a new class of frequency-switchable metamaterial absorber in the X-band. Eutectic gallium-indium (EGaIn), a liquid metal alloy, was injected in a microfluidic channel engraved on polymethyl methacrylate (PMMA) to achieve frequency switching. Numerical simulation and experimental results are presented for two cases: when the microfluidic channels are empty, and when they are filled with liquid metal. To evaluate the performance of the fabricated absorber prototype, it is tested with a rectangular waveguide. The resonant frequency was successfully switched from 10.96 GHz to 10.61 GHz after injecting liquid metal while maintaining absorptivity higher than 98%. PMID- 26561817 TI - PMHT Approach for Multi-Target Multi-Sensor Sonar Tracking in Clutter. AB - Multi-sensor sonar tracking has many advantages, such as the potential to reduce the overall measurement uncertainty and the possibility to hide the receiver. However, the use of multi-target multi-sensor sonar tracking is challenging because of the complexity of the underwater environment, especially the low target detection probability and extremely large number of false alarms caused by reverberation. In this work, to solve the problem of multi-target multi-sensor sonar tracking in the presence of clutter, a novel probabilistic multi-hypothesis tracker (PMHT) approach based on the extended Kalman filter (EKF) and unscented Kalman filter (UKF) is proposed. The PMHT can efficiently handle the unknown measurements-to-targets and measurements-to-transmitters data association ambiguity. The EKF and UKF are used to deal with the high degree of nonlinearity in the measurement model. The simulation results show that the proposed algorithm can improve the target tracking performance in a cluttered environment greatly, and its computational load is low. PMID- 26561816 TI - The Synthesis and Anion Recognition Property of Symmetrical Chemosensors Involving Thiourea Groups: Theory and Experiments. AB - The synthesis of four symmetrical compounds containing urea/thiourea and anthracene/nitrobenzene groups was optimized. N,N'-Di((anthracen-9-yl)-methylene) thio-carbonohydrazide showed sensitive and selective binding ability for acetate ion among the studied anions. The presence of other competitive anions including F(-), H2PO4(-), Cl(-), Br(-) and I(-) did not interfere with the strong binding ability. The mechanism of the host-guest interaction was through multiple hydrogen bonds due to the conformational complementarity and higher basicity. A theoretical investigation explained that intra-molecular hydrogen bonds existed in the compound which could strengthen the anion binding ability. In addition, molecular frontier orbitals in molecular interplay were introduced in order to explain the red-shift phenomenon in the host-guest interaction process. Compounds based on thiourea and anthracene derivatives can thus be used as a chemosensor for detecting acetate ion in environmental and pharmaceutical samples. PMID- 26561818 TI - Optimizing the Reliability and Performance of Service Composition Applications with Fault Tolerance in Wireless Sensor Networks. AB - The services composition technology provides flexible methods for building service composition applications (SCAs) in wireless sensor networks (WSNs). The high reliability and high performance of SCAs help services composition technology promote the practical application of WSNs. The optimization methods for reliability and performance used for traditional software systems are mostly based on the instantiations of software components, which are inapplicable and inefficient in the ever-changing SCAs in WSNs. In this paper, we consider the SCAs with fault tolerance in WSNs. Based on a Universal Generating Function (UGF) we propose a reliability and performance model of SCAs in WSNs, which generalizes a redundancy optimization problem to a multi-state system. Based on this model, an efficient optimization algorithm for reliability and performance of SCAs in WSNs is developed based on a Genetic Algorithm (GA) to find the optimal structure of SCAs with fault-tolerance in WSNs. In order to examine the feasibility of our algorithm, we have evaluated the performance. Furthermore, the interrelationships between the reliability, performance and cost are investigated. In addition, a distinct approach to determine the most suitable parameters in the suggested algorithm is proposed. PMID- 26561819 TI - A Dynamic Range Enhanced Readout Technique with a Two-Step TDC for High Speed Linear CMOS Image Sensors. AB - This paper presents a dynamic range (DR) enhanced readout technique with a two step time-to-digital converter (TDC) for high speed linear CMOS image sensors. A multi-capacitor and self-regulated capacitive trans-impedance amplifier (CTIA) structure is employed to extend the dynamic range. The gain of the CTIA is auto adjusted by switching different capacitors to the integration node asynchronously according to the output voltage. A column-parallel ADC based on a two-step TDC is utilized to improve the conversion rate. The conversion is divided into coarse phase and fine phase. An error calibration scheme is also proposed to correct quantization errors caused by propagation delay skew within -T(clk)~+T(clk). A linear CMOS image sensor pixel array is designed in the 0.13 MUm CMOS process to verify this DR-enhanced high speed readout technique. The post simulation results indicate that the dynamic range of readout circuit is 99.02 dB and the ADC achieves 60.22 dB SNDR and 9.71 bit ENOB at a conversion rate of 2 MS/s after calibration, with 14.04 dB and 2.4 bit improvement, compared with SNDR and ENOB of that without calibration. PMID- 26561820 TI - Seasonal Changes in Mycosporine-Like Amino Acid Production Rate with Respect to Natural Phytoplankton Species Composition. AB - After in situ incubation at the site for a year, phytoplanktons in surface water were exposed to natural light in temperate lakes (every month); thereafter, the net production rate of photoprotective compounds (mycosporine-like amino acids, MAAs) was calculated using (13)C labeled tracer. This is the first report describing seasonal variation in the net production rate of individual MAAs in temperate lakes using a compound-specific stable isotope method. In the mid latitude region of the Korean Peninsula, UV radiation (UVR) usually peaks from July to August. In Lake Paldang and Lake Cheongpyeong, diatoms dominated among the phytoplankton throughout the year. The relative abundance of Cyanophyceae (Anabaena spiroides) reached over 80% during July in Lake Cheongpyeong. Changes in phytoplankton abundance indicate that the phytoplankton community structure is influenced by seasonal changes in the net production rate and concentration of MAAs. Notably, particulate organic matter (POM) showed a remarkable change based on the UV intensity occurring during that period; this was because of the fact that cyanobacteria that are highly sensitive to UV irradiance dominated the community. POM cultured in Lake Paldang had the greatest shinorine (SH) production rate during October, i.e., 83.83 +/- 10.47 fgC.L(-1).h(-1). The dominance of diatoms indicated that they had a long-term response to UVR. Evaluation of POM cultured in Lake Cheongpyeong revealed that there was an increase in the net MAA production in July (when UVR reached the maximum); a substantial amount of SH, i.e., 17.62 +/- 18.34 fgC.L(-1).h(-1), was recorded during this period. Our results demonstrate that both the net production rate as well as the concentration of MAAs related to photoinduction depended on the phytoplankton community structure. In addition, seasonal changes in UVR also influenced the quantity and production of MAAs in phytoplanktons (especially Cyanophyceae). PMID- 26561821 TI - Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay. AB - The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV). We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95%) and low cytotoxicity (66% to 77%). Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy)-phenol (compound 1) and 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol (compound 2), which are classified as polybrominated diphenyl ethers (PBDEs), were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 uM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs. PMID- 26561822 TI - Heavy Metal Pollution, Fractionation, and Potential Ecological Risks in Sediments from Lake Chaohu (Eastern China) and the Surrounding Rivers. AB - Heavy metal (Cr, Ni, Cu, Zn, Cd, and Pb) pollution, fractionation, and ecological risks in the sediments of Lake Chaohu (Eastern China), its eleven inflowing rivers and its only outflowing river were studied. An improved BCR (proposed by the European Community Bureau of Reference) sequential extraction procedure was applied to fractionate heavy metals within sediments, a geoaccumulation index was used to assess the extent of heavy metal pollution, and a risk assessment code was applied to evaluate potential ecological risks. Heavy metals in the Shuangqiao and Nanfei Rivers were generally higher than the other studied sites. Of the three Lake Chaohu sites, the highest concentrations were identified in western Chaohu. Heavy metal pollution and ecological risks in the lake's only outflowing river were similar to those in the eastern region of the lake, to which the river is connected. Heavy metal concentrations occurred in the following order: Cd > Zn > Cu > Pb ~ Ni ~ Cr. Cr, Ni, and Cu made up the largest proportion of the residual fraction, while Cd was the most prominent metal in the exchangeable and carbonate-included fraction. Cd posed the greatest potential ecological risk; the heavy metals generally posed risks in the following order: Cd > Zn > Cu > Ni > Pb > Cr. PMID- 26561823 TI - Indoor Environmental Quality in Mechanically Ventilated, Energy-Efficient Buildings vs. Conventional Buildings. AB - Energy-efficient buildings need mechanical ventilation. However, there are concerns that inadequate mechanical ventilation may lead to impaired indoor air quality. Using a semi-experimental field study, we investigated if exposure of occupants of two types of buildings (mechanical vs. natural ventilation) differs with regard to indoor air pollutants and climate factors. We investigated living and bedrooms in 123 buildings (62 highly energy-efficient and 61 conventional buildings) built in the years 2010 to 2012 in Austria (mainly Vienna and Lower Austria). Measurements of indoor parameters (climate, chemical pollutants and biological contaminants) were conducted twice. In total, more than 3000 measurements were performed. Almost all indoor air quality and room climate parameters showed significantly better results in mechanically ventilated homes compared to those relying on ventilation from open windows and/or doors. This study does not support the hypothesis that occupants in mechanically ventilated low energy houses are exposed to lower indoor air quality. PMID- 26561824 TI - Distribution and Source of Polycyclic Aromatic Hydrocarbons (PAHs) in Water Dissolved Phase, Suspended Particulate Matter and Sediment from Weihe River in Northwest China. AB - Weihe River is a typical river located in the arid and semi-arid regions of Northwest China. In this study, the distribution and sources of 16 polycyclic aromatic hydrocarbons (PAHs) in Weihe River were investigated. The concentrations of ?PAHs ranged from 351 to 4427 ng/L with a mean value of 835.4 ng/L in water dissolved phase (WDP), from 3557 ng/L to 147,907 ng/L with a mean value of 20,780 ng /L in suspended particulate matter (SPM), and from 362 to 15,667 ng/g dry weight (dw) with a mean value of 2000 ng/g dw in sediment, respectively. The concentrations of PAHs in Weihe River were higher compared with other rivers in the world. In both WDP and sediment, the highest concentrations of ?PAHs were observed in the middle reach, while the lowest concentrations of ?PAHs were found in the lower reach. For SPM, however, the PAHs concentrations in the lower reach were highest and the PAHs concentrations in the upper reach were lowest. The ratios of anthracene/(anthracene + phenanthrene) and fluoranthene/ (fluoranthene + pyrene) reflected a pattern of both pyrolytic and petrogenic input of PAHs in Weihe River. The potential ecosystem risk assessment indicated that harmful biological impairments occur frequently in Weihe River. PMID- 26561825 TI - Nutritional Correlates of Perceived Stress among University Students in Egypt. AB - Food intake choice and amount might change with stress. However, this has not been examined among Egyptian students. We examined students' stress levels, its correlation with their consumption of a range of food groups, and adherence to dietary guidelines. A cross sectional survey (N = 2810 undergraduates at 11 faculties at Assiut University, Egypt) assessed two composite food intake pattern scores (one unhealthy: sweets, cakes, snacks; and a healthy one: fruits and vegetables), and two indicators of healthy eating (subjective importance of healthy eating; and dietary guideline adherence index). Multiple linear regression tested the associations of stress with two food intake pattern scores and two indicators of healthy eating, controlling for six potential confounders for the sample and separately for males and females. Higher perceived stress score was significantly associated with less frequent food intake of fruit and vegetables in males and females. The association was more pronounced among males than in females. No significant association was observed between the sweets cakes and snacks score and stress. Of the two indicators of healthy eating, the dietary guideline adherence index was not associated with stress, while the subjective judgment of healthy eating was consistently negatively associated with stress. Stress related decreased-eating was present. Recent studies suggest that stress could be associated with either decreased or increased eating depending on the study population, food group, and type of stressor. Further research is necessary to understand stress related over- and undereating. PMID- 26561826 TI - Exposure Knowledge and Perception of Wireless Communication Technologies. AB - The presented survey investigates risk and exposure perceptions of radio frequency electromagnetic fields (RF EMF) associated with base stations, mobile phones and other sources, the key issue being the interaction between both sets of perceptions. The study is based on a cross-sectional design, and conducted with an online sample of 838 citizens from Portugal. The results indicate that respondents' intuitive exposure perception differs from the actual exposure levels. Furthermore, exposure and risk perceptions are found to be highly correlated. Respondents' beliefs about exposure factors, which might influence possible health risks, is appropriate. A regression analysis between exposure characteristics, as predictor variables, and RF EMF risk perception, as the response variable, indicates that people seem to use simple heuristics to form their perceptions. What is bigger, more frequent and longer lasting is seen as riskier. Moreover, the quality of exposure knowledge is not an indicator for amplified EMF risk perception. These findings show that exposure perception is key to future risk communication. PMID- 26561828 TI - Oncolytic Replication of E1b-Deleted Adenoviruses. AB - Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads) are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption. PMID- 26561827 TI - Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications. AB - Selection of inhibitor-resistant viral mutants is universal for viruses that display quasi-species dynamics, and hepatitis C virus (HCV) is no exception. Here we review recent results on drug resistance in HCV, with emphasis on resistance to the newly-developed, directly-acting antiviral agents, as they are increasingly employed in the clinic. We put the experimental observations in the context of quasi-species dynamics, in particular what the genetic and phenotypic barriers to resistance mean in terms of exploration of sequence space while HCV replicates in the liver of infected patients or in cell culture. Strategies to diminish the probability of viral breakthrough during treatment are briefly outlined. PMID- 26561829 TI - Immunostimulatory Gene Therapy Using Oncolytic Viruses as Vehicles. AB - Immunostimulatory gene therapy has been developed during the past twenty years. The aim of immunostimulatory gene therapy is to tilt the suppressive tumor microenvironment to promote anti-tumor immunity. Hence, like a Trojan horse, the gene vehicle can carry warriors and weapons into enemy territory to combat the tumor from within. The most promising immune stimulators are those activating and sustaining Th1 responses, but even if potent effects were seen in preclinical models, many clinical trials failed to show objective responses in cancer patients. However, with new tools to control ongoing immunosuppression in cancer patients, immunostimulatory gene therapy is now emerging as an interesting option. In parallel, oncolytic viruses have been shown to be safe in patients. To prolong immune stimulation and to increase efficacy, these two fields are now merging and oncolytic viruses are armed with immunostimulatory transgenes. These novel agents are racing towards approval as established cancer immunotherapeutics. PMID- 26561830 TI - Iron Metabolism Dysregulation and Cognitive Dysfunction in Pediatric Obesity: Is There a Connection? AB - Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research. PMID- 26561831 TI - Diet, Microbiota and Immune System in Type 1 Diabetes Development and Evolution. AB - Type 1 diabetes (T1D) is the second most frequent autoimmune disease in childhood. The long-term micro- and macro-vascular complications of diabetes are associated with the leading causes of disability and even mortality in young adults. Understanding the T1D etiology will allow the design of preventive strategies to avoid or delay the T1D onset and to help to maintain control after developing. T1D development involves genetic and environmental factors, such as birth delivery mode, use of antibiotics, and diet. Gut microbiota could be the link between environmental factors, the development of autoimmunity, and T1D. In this review, we will focus on the dietary factor and its relationship with the gut microbiota in the complex process involved in autoimmunity and T1D. The molecular mechanisms involved will also be addressed, and finally, evidence-based strategies for potential primary and secondary prevention of T1D will be discussed. PMID- 26561833 TI - Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy. AB - Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP. PMID- 26561834 TI - Revealing the Complexity of Breast Cancer by Next Generation Sequencing. AB - Over the last few years the increasing usage of "-omic" platforms, supported by next-generation sequencing, in the analysis of breast cancer samples has tremendously advanced our understanding of the disease. New driver and passenger mutations, rare chromosomal rearrangements and other genomic aberrations identified by whole genome and exome sequencing are providing missing pieces of the genomic architecture of breast cancer. High resolution maps of breast cancer methylomes and sequencing of the miRNA microworld are beginning to paint the epigenomic landscape of the disease. Transcriptomic profiling is giving us a glimpse into the gene regulatory networks that govern the fate of the breast cancer cell. At the same time, integrative analysis of sequencing data confirms an extensive intertumor and intratumor heterogeneity and plasticity in breast cancer arguing for a new approach to the problem. In this review, we report on the latest findings on the molecular characterization of breast cancer using NGS technologies, and we discuss their potential implications for the improvement of existing therapies. PMID- 26561832 TI - The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring. AB - The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams' diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring. PMID- 26561835 TI - Multiparametric Evaluation of Head and Neck Squamous Cell Carcinoma Using a Single-Source Dual-Energy CT with Fast kVp Switching: State of the Art. AB - There is an increasing body of evidence establishing the advantages of dual energy CT (DECT) for evaluation of head and neck squamous cell carcinoma (HNSCC). Focusing on a single-source DECT system with fast kVp switching, we will review the principles behind DECT and associated post-processing steps that make this technology especially suitable for HNSCC evaluation and staging. The article will review current applications of DECT for evaluation of HNSCC including use of different reconstructions to improve tumor conspicuity, tumor-normal soft tissue interface, accuracy of invasion of critical structures such as thyroid cartilage, and reduce dental artifact. We will provide a practical approach for DECT implementation into routine clinical use and a multi-parametric approach for scan interpretation based on the experience at our institution. The article will conclude with a brief overview of potential future applications of the technique. PMID- 26561836 TI - The Classification of Hysteria and Related Disorders: Historical and Phenomenological Considerations. AB - This article examines the history of the conceptualization of dissociative, conversion, and somatoform syndromes in relation to one another, chronicles efforts to classify these and other phenomenologically-related psychopathology in the American diagnostic system for mental disorders, and traces the subsequent divergence in opinions of dissenting sectors on classification of these disorders. This article then considers the extensive phenomenological overlap across these disorders in empirical research, and from this foundation presents a new model for the conceptualization of these disorders. The classification of disorders formerly known as hysteria and phenomenologically-related syndromes has long been contentious and unsettled. Examination of the long history of the conceptual difficulties, which remain inherent in existing classification schemes for these disorders, can help to address the continuing controversy. This review clarifies the need for a major conceptual revision of the current classification of these disorders. A new phenomenologically-based classification scheme for these disorders is proposed that is more compatible with the agnostic and atheoretical approach to diagnosis of mental disorders used by the current classification system. PMID- 26561837 TI - Neutrophil Development, Migration, and Function in Teleost Fish. AB - It is now widely recognized that neutrophils are sophisticated cells that are critical to host defense and the maintenance of homeostasis. In addition, concepts such as neutrophil plasticity are helping to define the range of phenotypic profiles available to cells in this group and the physiological conditions that contribute to their differentiation. Herein, we discuss key features of the life of a teleost neutrophil including their development, migration to an inflammatory site, and contributions to pathogen killing and the control of acute inflammation. The potent anti-microbial mechanisms elicited by these cells in bony fish are a testament to their long-standing evolutionary contributions in host defense. In addition, recent insights into their active roles in the control of inflammation prior to induction of apoptosis highlight their importance to the maintenance of host integrity in these early vertebrates. Overall, our goal is to summarize recent progress in our understanding of this cell type in teleost fish, and to provide evolutionary context for the contributions of this hematopoietic lineage in host defense and an efficient return to homeostasis following injury or infection. PMID- 26561839 TI - [The diagnosis of latent tuberculosis infection in children in XXI century. Is tuberculin skin test still up to date?]. AB - Tuberculosis morbidity rates in Poland have been gradually decreasing. Nevertheless, there are approximately 8 thousand cases being registered annually, which includes almost 3 thousand massively infectious patients. In the last 3 years, around 100 cases/year have been reported among children below 14 years of age. Infection with Mycobacterium tuberculosis should be considered in all patients who present symptoms suggesting tuberculosis, have had recent contact with a person suffering from lung tuberculosis or are planned to undergo an immunosuppressive treatment. HIV infected patients are also supposed to have screening tests for M. tuberculosis infection performed. For over a 100 years tuberculin skin test (TST) was the only test capable of confirming tuberculous infection. TST is based on the assessment of skin reaction to intracutaneous injection of tuberculin. Due to cross-reaction to the injected tuberculin in BCG vaccinated individuals, the correct interpretation of the test is difficult. Since 13 years new immunological assays have been available. They are based on detecting interferon gamma (Interferon Gamma Release Assay - IGRA) concentration in blood serum, which has previously been incubated with Mycobacterium tuberculosis antigens absent in the BCG strain. In infected individuals interferon gamma is intensively produced by memory cells in reaction to the contact with previously met Mycobacterium antigens. Many trials have proved IGRA's high sensitivity and, higher than TST, specificity. Recent guidelines promote the usage of IGRAs, even in children. PMID- 26561838 TI - Skin Immunization Obviates Alcohol-Related Immune Dysfunction. AB - Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. PMID- 26561840 TI - [Dental plaque as a biofilm - a risk in oral cavity and methods to prevent]. AB - Bacteria living constantly in the oral cavity are in the form of a biofilm. The biofilm formed on a solid base such as the enamel of the teeth, fillings, restorations, orthodontic appliances or obturators is dental plaque. Disturbance of homeostasis of biofilm, excessive growth or increase in the number of acid forming bacteria leads to the development of the most common diseases of the oral cavity, i.e. dental caries and periodontal disease. The presence of bacterial biofilm on the walls of the root canal or at the top of the root on an outer wall leads to complications and failure in endodontic treatment. The aim of the study was to present the latest information on the occurrence, development and the role of biofilm in the etiopathogenesis of oral diseases and its control. Based on the literature analyzed, it can be concluded that the biofilm, due to its complex structure and numerous mechanisms of bacteria adaptation, is an effective barrier against the traditional agents with antibacterial properties. There are now great hopes for nanotechnology as an innovative method for obtaining new structures of nanometric size and different properties than source materials. The use of antibacterial properties of nano-silver used in dentistry significantly reduces the metabolic activity and the number of colony forming bacteria and lactic acid production in the biofilm. PMID- 26561841 TI - [Heat shock protein HSP60 and the perspective for future using as vaccine antigens]. AB - Heat Shock Proteins (HSPs) are widely spread in nature, highly conserved proteins, found in all prokaryotic and eukaryotic cells. HSPs have been classified in 10 families, one of them is the HSP60 family. HSP60 function in the cytoplasm as ATP-dependent molecular chaperones by assisting the folding of newly synthesised polypeptides and the assembly of multiprotein complexes. There is a large amount of evidence which demonstrate that HSP60 is expressed on the cell surface. Especially in bacteria the expression on the surface occurs constitutively and increases remarkably during host infection. HSP60 also play an important role in biofilm formation. In the extracellular environment, HSP60 alone or with self or microbial proteins can acts not only as a link between immune cells, but also as a coordinator of the immune system activity. This protein could influence the immune system in a different way because they act as an antigen, a carrier of other functional molecules or as a ligand for receptor. They are able to stimulate both cells of the acquired (naive, effector, regulatory T lymphocyte, B lymphocyte) and the innate (macrophages, monocytes, dendritic cells) immune system. HSPs have been reported to be potent activators of the immune system and they are one of the immunodominant bacterial antigens they could be a good candidate for a subunit vaccine or as an adjuvant. PMID- 26561842 TI - [The neurotoxicity of pyridinium metabolites of haloperidol]. AB - Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS). The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT) to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration. PMID- 26561843 TI - Bone markers in craniofacial bone deformations and dysplasias. AB - Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not only present in the skull but also can be found in other parts of the skeleton. In many cases the presence and levels of specific bone markers should be measured in order to fully describe their activity and presence in the skeleton. Fibrous dysplasia (FD) is the most common one in the facial skeleton; however, other bone deformations regarding bone growth and activity can also be present. Every clinician should be aware of all common, rare and uncommon bony diseases and conditions such as cherubism, Paget's disease, osteogenesis imperfecta and others related to genetic conditions. We present standard (calcium, parathyroid hormone, calcitonin, alkaline phosphatase, vitamin D) and specialized bone markers (pyridinium, deoxypyridinium, hydroxyproline, RANKL/RANK/OPG pathway, growth hormone, insulin-like growth hormone-1) that can be used to evaluate, measure or describe the processes occurring in craniofacial bones. PMID- 26561844 TI - Pneumococcal and seasonal influenza vaccination among elderly patients with diabetes. AB - Both seasonal influenza vaccination and pneumococcal vaccination are recommended for elderly diabetics. The aim of the study was to determine the rate of seasonal influenza vaccination over the previous twelve months, pneumococcal vaccination over a lifetime, and to identify predictors which affect likelihood of vaccination. 219 diabetics elders were detailed questioned 3 months after the end of 2012/2013 influenza season. 26.48% of patients have been vaccinated against influenza in the last year and only 9.13% of patients reported pneumococcal vaccination in the past. The logistic regression analysis revealed that variables which increased the likelihood of having been vaccinated against influenza were: higher number of anti-hyperglycemic medications, increased number of co morbidities, higher patients' income, recommendation of vaccination from General Practitioners (GPs) and specialist. Significant predictors of pneumococcal vaccine uptake included increased number of co-morbidities and recommendation of vaccination received from GPs and specialist. The commonest reasons given by those unvaccinated were lack of information about immunization and low perceived benefits of vaccination. Of patients who were not treated with influenza vaccine 86.7% had never received recommendation from specialist and 71.4% had never been advised by GPs. Influenza vaccination was too expensive to 24.85% of patients. The vaccination rate among elderly diabetics in Poland is low. Lack of knowledge and patients' income are the main barriers. Increased awareness of healthcare professionals to educate and encourage vaccination and propagation of free vaccinations to all people at risk may increase the rate of vaccination against influenza and pneumococcal disease. PMID- 26561845 TI - Saliva of obese patients - is it different? AB - Obesity is a major public health concern that increases the risk of cardiovascular disease, type 2 diabetes and cancer. The incidence of obesity has increased significantly in recent years, not only in adults, but also in adolescents and children. This is evidenced by rapidly developing bariatric surgery, the most effective method of treating morbid obesity. Obesity is a multifactorial disease, and its pathogenesis is not completely understood. Numerous studies have been performed to clarify pathogenetic mechanisms, based mostly on blood and sometimes urine samples. Saliva is easily accessible and can be obtained non-invasively. Our aim was to review studies performed on saliva obtained from obese subjects in order to answer the title question. Obese people have different composition of salivary bacteria. Changes in the concentration of sialic acid, phosphorus and peroxidase activity as well as a lower flow rate of stimulated whole saliva promote dental caries and periodontal disease. Concentrations of salivary uric acid, endocannabinoids and CRP are increased in obesity and may provide a useful index of cardiometabolic risk. Assessment of fasting salivary ghrelin might facilitate choosing the best type of bariatric surgery for a specific patient. A significant decrease in salivary cortisol in women with morbid obesity also seems interesting. There is sufficient evidence to state that the saliva of obese and lean subjects is different. Saliva as an easily accessible research material seems promising, as shown by the few studies performed so far. PMID- 26561846 TI - Medical applications of nanotechnology. AB - Nanotechnologies are new areas of research focusing on affecting matter at the atomic and molecular levels. It is beyond doubt that modern medicine can benefit greatly from it; thus nanomedicine has become one of the main branches of nanotechnological research. Currently it focuses on developing new methods of preventing, diagnosing and treating various diseases. Nanomaterials show very high efficiency in destroying cancer cells and are already undergoing clinical trials. The results are so promising that nanomaterials might become an alternative to traditional cancer therapy, mostly due to the fact that they allow cancer cells to be targeted specifically and enable detailed imaging of tissues, making planning further therapy much easier. Nanoscience might also be a source of the needed breakthrough in the fight against atherosclerosis, since nanostructures may be used in both preventing and increasing the stability of atherosclerotic lesions. One area of interest is creating nanomaterials that are not only efficient, but also well tolerated by the human body. Other potential applications of nanotechnology in medicine include: nanoadjuvants with immunomodulatory properties used to deliver vaccine antigens; the nano-knife, an almost non-invasive method of destroying cancer cells with high voltage electricity; and carbon nanotubes, which are already a popular way of repairing damaged tissues and might be used to regenerate nerves in the future. The aim of this article is to outline the potential uses of nanotechnology in medicine. Original articles and reviews have been used to present the new developments and directions of studies. PMID- 26561847 TI - [Angiogenesis and lymphangiogenesis in primary cutaneous T-cell lymphomas]. AB - Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments. PMID- 26561848 TI - Thrombocytopenia in pregnancy - pathogenesis and diagnostic approach. AB - Thrombocytopenia (TP) affects 7-10% of pregnant women. It occurs 4 times more frequently in pregnancy than in the non-pregnant women population. Women with thrombocytopenia in pregnancy are a heterogeneous and poorly known group. There are several possible causes of thrombocytopenia in pregnancy. The most common are: gestational thrombocytopenia (GE) (60-75%), preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome associated TP (21%), and idiopathic immune thrombocytopenia (ITP) (3-10%). Although thrombocytopenia diagnosed in pregnancy in most cases has a mild course, it has also been reported to be associated with a higher rate of preterm birth and premature detachment of the placenta. Some cases of severe thrombocytopenia with systemic involvement are associated with high risk of serious perinatal complications and require early diagnosis, careful clinical monitoring and medical treatment. The differential diagnosis and proper assessment of clinical risk of TP during pregnancy may be of great concern. The article discusses these issues, focusing on pathophysiology of TP in pregnancy. PMID- 26561849 TI - Analysis of nanomechanical properties of Borrelia burgdorferi spirochetes under the influence of lytic factors in an in vitro model using atomic force microscopy. AB - BACKGROUND: Atomic force microscopy (AFM) is an experimental technique which recently has been used in biology, microbiology, and medicine to investigate the topography of surfaces and in the evaluation of mechanical properties of cells. The aim of this study was to evaluate the influence of the complement system and specific anti-Borrelia antibodies in in vitro conditions on the modification of nanomechanical features of B. burgdorferi B31 cells. MATERIAL AND METHODS: In order to assess the influence of the complement system and anti-Borrelia antibodies on B. burgdorferi s.s. B31 spirochetes, the bacteria were incubated together with plasma of identified status. The samples were applied on the surface of mica disks. Young's modulus and adhesive forces were analyzed with a NanoScope V, MultiMode 8 AFM microscope (Bruker) by the PeakForce QNM technique in air using NanoScope Analysis 1.40 software (Bruker). RESULTS/CONCLUSION: The average value of flexibility of spirochetes' surface expressed by Young's modulus was 10185.32 MPa, whereas the adhesion force was 3.68 nN. AFM is a modern tool with a broad spectrum of observational and measurement abilities. Young's modulus and the adhesion force can be treated as parameters in the evaluation of intensity and changes which take place in pathogenic microorganisms under the influence of various lytic factors. The visualization of the changes in association with nanomechanical features provides a realistic portrayal of the lytic abilities of the elements of the innate and adaptive human immune system. PMID- 26561850 TI - [Novel aspects of human infertility: the role of the male factor]. AB - In the article new aspects of the 'male factor' and its role in early stages of pregnancy are described. Among others, genetic and immunogenetic (KIR/KAR, HLA) factors are underlined as well as immunological ones (e.g. microchimerism). A significant part of this review is dedicated to infectious agents and semen inflammation as well as to the TORCH syndrome and chlamydiosis, concentrating on the male part, in which there are a lot of unclarified consequences. The problem of somatic diseases and general homeostasis of the male and its influence on pregnancy with particular emphasis on previous cryptorchidism is also discussed. The role of sperm DNA integrity in the fertilization process as well as genetic polymorphisms on the male side is emphasised. Particularly, molecular aspects of HLA-G and HLA-C in developmental biology are raised. There is a discussion of the individual approach to assisted reproductive techniques, which cannot be treated as a panacea for infertility treatment, particularly considering early stages of embryonal and fetal development. PMID- 26561852 TI - Coevolved Mutations Reveal Distinct Architectures for Two Core Proteins in the Bacterial Flagellar Motor. AB - Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc alpha-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity. PMID- 26561851 TI - RNA-seq Brings New Insights to the Intra-Macrophage Transcriptome of Salmonella Typhimurium. AB - Salmonella enterica serovar Typhimurium is arguably the world's best-understood bacterial pathogen. However, crucial details about the genetic programs used by the bacterium to survive and replicate in macrophages have remained obscure because of the challenge of studying gene expression of intracellular pathogens during infection. Here, we report the use of deep sequencing (RNA-seq) to reveal the transcriptional architecture and gene activity of Salmonella during infection of murine macrophages, providing new insights into the strategies used by the pathogen to survive in a bactericidal immune cell. We characterized 3583 transcriptional start sites that are active within macrophages, and highlight 11 of these as candidates for the delivery of heterologous antigens from Salmonella vaccine strains. A majority (88%) of the 280 S. Typhimurium sRNAs were expressed inside macrophages, and SPI13 and SPI2 were the most highly expressed pathogenicity islands. We identified 31 S. Typhimurium genes that were strongly up-regulated inside macrophages but expressed at very low levels during in vitro growth. The SalComMac online resource allows the visualisation of every transcript expressed during bacterial replication within mammalian cells. This primary transcriptome of intra-macrophage S.-Typhimurium describes the transcriptional start sites and the transcripts responsible for virulence traits, and catalogues the sRNAs that may play a role in the regulation of gene expression during infection. PMID- 26561853 TI - Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response. AB - Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-kappaB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health. PMID- 26561854 TI - Association of Early Atherosclerosis with Vascular Wall Shear Stress in Hypercholesterolemic Zebrafish. AB - Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis. PMID- 26561855 TI - Enhancer Runaway and the Evolution of Diploid Gene Expression. AB - Evidence is mounting that the evolution of gene expression plays a major role in adaptation and speciation. Understanding the evolution of gene regulatory regions is indeed an essential step in linking genotypes and phenotypes and in understanding the molecular mechanisms underlying evolutionary change. The common view is that expression traits (protein folding, expression timing, tissue localization and concentration) are under natural selection at the individual level. Here, we use a theoretical approach to show that, in addition, in diploid organisms, enhancer strength (i.e., the ability of enhancers to activate transcription) may increase in a runaway process due to competition for expression between homologous enhancer alleles. These alleles may be viewed as self-promoting genetic elements, as they spread without conferring a benefit at the individual level. They gain a selective advantage by getting associated to better genetic backgrounds: deleterious mutations are more efficiently purged when linked to stronger enhancers. This process, which has been entirely overlooked so far, may help understand the observed overrepresentation of cis acting regulatory changes in between-species phenotypic differences, and sheds a new light on investigating the contribution of gene expression evolution to adaptation. PMID- 26561856 TI - Claudin-6 and Occludin Natural Variants Found in a Patient Highly Exposed but Not Infected with Hepatitis C Virus (HCV) Do Not Confer HCV Resistance In Vitro. AB - The clinical course of Hepatitis C Virus (HCV) infection is highly variable between infected individual hosts: up to 80% of acutely HCV infected patients develop a chronic infection while 20% clear infection spontaneously. Spontaneous clearance of HCV infection can be predicted by several factors, including symptomatic acute infection, favorable IFNL3 polymorphisms and gender. In our study, we explored the possibility that variants in HCV cell entry factors might be involved in resistance to HCV infection. In a same case patient highly exposed but not infected by HCV, we previously identified one mutation in claudin-6 (CLDN6) and a rare variant in occludin (OCLN), two tight junction proteins involved in HCV entry into hepatocytes. Here, we conducted an extensive functional study to characterize the ability of these two natural variants to prevent HCV entry. We used lentiviral vectors to express Wildtype or mutated CLDN6 and OCLN in different cell lines and primary human hepatocytes. HCV infection was then investigated using cell culture produced HCV particles (HCVcc) as well as HCV pseudoparticles (HCVpp) expressing envelope proteins from different genotypes. Our results show that variants of CLDN6 and OCLN expressed separately or in combination did not affect HCV infection nor cell-to-cell transmission. Hence, our study highlights the complexity of HCV resistance mechanisms supporting the fact that this process probably not primarily involves HCV entry factors and that other unknown host factors may be implicated. PMID- 26561857 TI - Physical Characterization of Gemini Surfactant-Based Synthetic Vectors for the Delivery of Linear Covalently Closed (LCC) DNA Ministrings. AB - In combination with novel linear covalently closed (LCC) DNA minivectors, referred to as DNA ministrings, a gemini surfactant-based synthetic vector for gene delivery has been shown to exhibit enhanced delivery and bioavailability while offering a heightened safety profile. Due to topological differences from conventional circular covalently closed (CCC) plasmid DNA vectors, the linear topology of LCC DNA ministrings may present differences with regards to DNA interaction and the physicochemical properties influencing DNA-surfactant interactions in the formulation of lipoplexed particles. In this study, N,N bis(dimethylhexadecyl)-alpha,omega-propanediammonium(16-3-16)gemini-based synthetic vectors, incorporating either CCC plasmid or LCC DNA ministrings, were characterized and compared with respect to particle size, zeta potential, DNA encapsulation, DNase sensitivity, and in vitro transgene delivery efficacy. Through comparative analysis, differences between CCC plasmid DNA and LCC DNA ministrings led to variations in the physical properties of the resulting lipoplexes after complexation with 16-3-16 gemini surfactants. Despite the size disparities between the plasmid DNA vectors (CCC) and DNA ministrings (LCC), differences in DNA topology resulted in the generation of lipoplexes of comparable particle sizes. The capacity for ministring (LCC) derived lipoplexes to undergo complete counterion release during lipoplex formation contributed to improved DNA encapsulation, protection from DNase degradation, and in vitro transgene delivery. PMID- 26561858 TI - Aspirin Compared to Low Intensity Anticoagulation in Patients with Non-Valvular Atrial Fibrillation. A Systematic Review and Meta-Analysis. AB - BACKGROUND: Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin. METHODS: We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure. RESULTS: Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57-1.56), major bleeding OR 1.06 (95% CI 0.42-2.62) or vascular death OR 1.04 (95% CI 0.61-1.75). The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12-2.48). CONCLUSION: In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation. PMID- 26561860 TI - Correction: Improving the pH-stability of Versatile Peroxidase by Comparative Structural Analysis with a Naturally-Stable Manganese Peroxidase. PMID- 26561859 TI - Implant Optimisation for Primary Hip Replacement in Patients over 60 Years with Osteoarthritis: A Cohort Study of Clinical Outcomes and Implant Costs Using Data from England and Wales. AB - BACKGROUND: Hip replacement is one of the most commonly performed surgical procedures worldwide; hundreds of implant configurations provide options for femoral head size, joint surface material and fixation method with dramatically varying costs. Robust comparative evidence to inform the choice of implant is needed. This retrospective cohort study uses linked national databases from England and Wales to determine the optimal type of replacement for patients over 60 years undergoing hip replacement for osteoarthritis. METHODS AND FINDINGS: Implants included were the commonest brand from each of the four types of replacement (cemented, cementless, hybrid and resurfacing); the reference prosthesis was the cemented hip procedure. Patient reported outcome scores (PROMs), costs and risk of repeat (revision) surgery were examined. Multivariable analyses included analysis of covariance to assess improvement in PROMs (Oxford hip score, OHS, and EQ5D index) (9159 linked episodes) and competing risks modelling of implant survival (79,775 procedures). Cost of implants and ancillary equipment were obtained from National Health Service procurement data. RESULTS: EQ5D score improvements (at 6 months) were similar for all hip replacement types. In females, revision risk was significantly higher in cementless hip prostheses (hazard ratio, HR = 2.22, p<0.001), when compared to the reference hip. Although improvement in OHS was statistically higher (22.1 versus 20.5, p<0.001) for cementless implants, this small difference is unlikely to be clinically important. In males, revision risk was significantly higher in cementless (HR = 1.95, p = 0.003) and resurfacing implants, HR = 3.46, p<0.001), with no differences in OHS. Material costs were lowest with the reference implant (cemented, range L1103 to L1524) and highest with cementless implants (L1928 to L4285). Limitations include the design of the study, which is intrinsically vulnerable to omitted variables, a paucity of long-term implant survival data (reflecting the duration of data collection), the possibility of revision under reporting, response bias within PROMs data, and issues associated with current outcome scoring systems, which may not accurately reflect level of improvement in some patients. CONCLUSIONS: Cement fixation, using a polyethylene cup and a standard sized head offers good outcomes, with the lowest risks and at the lowest costs. The most commonly used cementless and resurfacing implants were associated with higher risk of revision and were more costly, while perceptions of improved function and longevity were unsupported. PMID- 26561861 TI - GABRB2 Haplotype Association with Heroin Dependence in Chinese Population. AB - Substance dependence is a frequently observed comorbid disorder in schizophrenia, but little is known about genetic factors possibly shared between the two psychotic disorders. GABRB2, a schizophrenia candidate gene coding for GABAA receptor beta2 subunit, is examined for possible association with heroin dependence in Han Chinese population. Four single nucleotide polymorphisms (SNPs) in GABRB2, namely rs6556547 (S1), rs1816071 (S3), rs18016072 (S5), and rs187269 (S29), previously associated with schizophrenia, were examined for their association with heroin dependence. Two additional SNPs, rs10051667 (S31) and rs967771 (S32), previously associated with alcohol dependence and bipolar disorder respectively, were also analyzed. The six SNPs were genotyped by direct sequencing of PCR amplicons of target regions for 564 heroin dependent individuals and 498 controls of Han Chinese origin. Interestingly, it was found that recombination between the haplotypes of all-derived-allele (H1; OR = 1.00) and all-ancestral-allele (H2; OR = 0.74) at S5-S29 junction generated two recombinants H3 (OR = 8.51) and H4 (OR = 5.58), both conferring high susceptibility to heroin dependence. Additional recombination between H2 and H3 haplotypes at S1-S3 junction resulted in a risk-conferring haplotype H5 (OR = 1.94x109). In contrast, recombination between H1 and H2 haplotypes at S3-S5 junction rescued the risk-conferring effect of recombination at S5-S29 junction, giving rise to the protective haplotype H6 (OR = 0.68). Risk-conferring effects of S1-S3 and S5-S29 crossovers and protective effects of S3-S5 crossover were seen in both pure heroin dependent and multiple substance dependence subgroups. In conclusion, significant association was found with haplotypes of the S1-S29 segment in GABRB2 for heroin dependence in Han Chinese population. Local recombination was an important determining factor for switching haplotypes between risk-conferring and protective statuses. The present study provide evidence for the schizophrenia candidate gene GABRB2 to play a role in heroin dependence, but replication of these findings is required. PMID- 26561862 TI - Development of a Performance-Based Measure of Executive Functions in Patients with Schizophrenia. AB - A performance-based measure for assessing executive functions (EF) is useful to understand patients' real life performance of EF. This study aimed to develop a performance-based measure of executive functions (PEF) based on the Lezak model and to examine psychometric properties (i.e., unidimensionality and reliability) of the PEF using Rasch analysis in patients with schizophrenia. We developed the PEF in three phases: (1) designing the preliminary version of PEF; (2) consultation with experts, cognitive interviews with patients, and pilot tests on patients to revise the preliminary PEF; (3) establishment of the final version of the PEF and examination of unidimensionality and Rasch reliability. Two hundred patients were assessed using the revised PEF. After deleting items which did not satisfy the Rasch model's expectations, the final version of the PEF contained 1 practice item and 13 test items for assessing the four domains of EF (i.e., volition, planning, purposive action, and effective performance). For unidimensional and multidimensional Rasch analyses, the 4 domains showed good reliability (i.e., 0.77-0.85 and 0.87-0.90, respectively). Our results showed that the PEF had satisfactory unidimensionality and Rasch reliability. Therefore, clinicians and researchers could use the PEF to assess the four domains of EF in patients with schizophrenia. PMID- 26561864 TI - Sex Differences in Participation, Performance, and Age of Ultramarathon Runners. AB - The sex difference in marathon running is increased with lower participation of women than men, but whether this occurs for ultramarathon running is not known. The study purpose was to determine whether the sex difference in performance widens among lower-placed runners and the association between the sex difference in running speed and participation rates. The top-10 ultramarathon running times, age at performance date, and the number of men and women finishers were analyzed from 20 races (45-160 km) in the US Track and Field Ultra Running Grand Prix. Men were faster than women for all events (18.7% +/- 5.8%, P < .001). The sex difference in speed was the least for 100 km (14.9% +/- 4.2%) and greatest for 45 50 km (19.3% +/- 5.8%). The top-10 men were younger than the top-10 women (37.7 +/- 3.2 and 39.0 +/- 3.1 y, respectively, P < .001). The sex difference in speed increased with finishing place (1st place 15.6% +/- 6.6% vs 10th 20.8% +/- 5.6%, P < .001). Association analysis showed that the sex difference in speed was largest when there were fewer women than men finishers in a race; the strength of the association was greatest for the 80-km distance and least for the 160-km. Lower participation rates of women than men in the lower-distance ultramarathons and less depth among lower-placed women runners inflate the sex difference in ultramarathon performance. PMID- 26561863 TI - Plant Photosynthesis-Irradiance Curve Responses to Pollution Show Non-Competitive Inhibited Michaelis Kinetics. AB - Photosynthesis-irradiance (PI) curves are extensively used in field and laboratory research to evaluate the photon-use efficiency of plants. However, most existing models for PI curves focus on the relationship between the photosynthetic rate (Pn) and photosynthetically active radiation (PAR), and do not take account of the influence of environmental factors on the curve. In the present study, we used a new non-competitive inhibited Michaelis-Menten model (NIMM) to predict the co-variation of Pn, PAR, and the relative pollution index (I). We then evaluated the model with published data and our own experimental data. The results indicate that the Pn of plants decreased with increasing I in the environment and, as predicted, were all fitted well by the NIMM model. Therefore, our model provides a robust basis to evaluate and understand the influence of environmental pollution on plant photosynthesis. PMID- 26561865 TI - Biocompatible Mesoporous Nanotubular Structured Surface to Control Cell Behaviors and Deliver Bioactive Molecules. AB - Biocompatible nanostructured surfaces control the cell behaviors and tissue integration process of medical devices and implants. Here we develop a novel biocompatible nanostructured surface based on mesoporous silica nanotube (MSNT) by means of an electrodeposition. MSNTs, replicated from carbon nanotubes of 25 nm * 1200 nm size, were interfaced in combination with fugitive biopolymers (chitosan or collagen) onto a Ti metallic substrate. The MSNT-biopolymer deposits uniformly covered the substrate with weight gains controllable by the electrodeposition conditions. Random nanotubular networks were generated successfully, which alongside the high mesoporosity provided unique nanotopological properties for the cell responses and the loading/delivery of biomolecules. Of note, the adhesion and spreading behaviors of mesenchymal stem cells (MSCs) were significantly altered, revealing more rapid cell anchorage and extensive nanofilopodia development along the nanotubular networks. Furthermore, the nanotubular surface improved the loading capacity of biomolecules (dexamethasone and bovine serum albumin) up to 5-7 times. The release of the biomolecules was highly sustained, exhibiting a diffusion-controlled pattern over 15 days. The therapeutic efficacy of the delivered biomolecules was also confirmed in the osteogenic differentiation of MSCs. While in vivo performance and applicability studies are needed further, the current biocompatible nanostructured surface may be considered as a novel biointerfacing platform to control cellular behaviors and biomolecular delivery. PMID- 26561866 TI - Cytotoxic Orbitide from the Latex of Croton urucurana. AB - The bioactive ethyl acetate phase obtained from the latex of Croton urucurana Baillon afforded a novel orbitide (1), [1-9-NalphaC]-crourorb A1, that proved active against NCI-ADR/RES (ovary, multidrug-resistance phenotype) cells with the same potency as doxorubicin (positive control) and inactive up to the highest concentration tested against nontumor NIH/3T3 cells. The structure elucidation was based on 1D and 2D NMR spectroscopy, further supported by HRESIMS data and by application of Marfey's method for determination of the absolute configuration of its amino acid residues. This is the first orbitide obtained from C. urucurana. PMID- 26561867 TI - Short-Lived Buildings in China: Impacts on Water, Energy, and Carbon Emissions. AB - This paper has changed the vague understanding that "the short-lived buildings have huge environmental footprints (EF)" into a concrete one. By estimating the annual floor space of buildings demolished and calibrating the average building lifetime in China, this paper compared the EF under various assumptive extended buildings' lifetime scenarios based on time-series environmental-extended input output model. Results show that if the average buildings' lifetime in China can be extended from the current 23.2 years to their designed life expectancy, 50 years, in 2011, China can reduce 5.8 Gt of water withdrawal, 127.1 Mtce of energy consumption, and 426.0 Mt of carbon emissions, each of which is equivalent to the corresponding annual EF of Belgium, Mexico, and Italy. These findings will urge China to extend the lifetime of existing and new buildings, in order to reduce the EF from further urbanization. This paper also verifies that the lifetime of a product or the replacement rate of a sector is a very important factor that influences the cumulative EF. When making policies to reduce the EF, adjusting people's behaviors to extend the lifetime of products or reduce the replacement rate of sectors may be a very simple and cost-effective option. PMID- 26561868 TI - Coordination-Driven Polymerization of Supramolecular Nanocages. AB - Controlled assembly of 0D supramolecular nanocages into 2D or 3D architectures has been demonstrated for the first time via a coordination-driven polymerization approach, and the conversion from a 2D to 3D supramolecular architecture has also been successfully achieved via a temperature-induced crystal transformation. The boost of dimensionality for the supramolecular architecture has led to steady yet remarkable enhancement of properties, as reflected from the gas adsorption studies. PMID- 26561869 TI - 2-Bromotetraazapentacene and Its Functionalization by Pd(0)-Chemistry. AB - We have synthesized a brominated N,N'-dihydrotetraazapentacene using a condensation route. Sonogashira reactions replace the Br-substituent by an alkynyl group, placed on the azaacene core. Sonogashira coupling of brominated dihydro tetraazapentacene 1H2 with alkynes and subsequent oxidation afford several functionalized TIPS-tetraazapentacene derivatives with energetically stabilized FMOs. These TIPS-TAPs are either crystalline or amorphous, depending upon their substitution pattern. PMID- 26561870 TI - Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes. AB - Although the "missing protein" is a temporary concept in C-HPP, the biological information for their "missing" could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 proteins (with no transcript evidence). These missing-protein-encoding genes distribute unevenly among different chromosomes, chromosomal regions, or gene clusters. In the view of evolutionary features, PE3/4 genes tend to be young, spreading at the nonhomology chromosomal regions and evolving at higher rates. Interestingly, there is a higher proportion of singletons in PE3/4 genes than the proportion of singletons in all genes (background) and OTCSGs (organ, tissue, cell type-specific genes). More importantly, most of the paralogous PE3/4 genes belong to the newly duplicated members of the paralogous gene groups, which mainly contribute to special biological functions, such as "smell perception". These functions are heavily restricted into specific type of cells, tissues, or specific developmental stages, acting as the new functional requirements that facilitated the emergence of the missing-protein-encoding genes during evolution. In addition, the criteria for the extremely special physical-chemical proteins were first set up based on the properties of PE2 proteins, and the evolutionary characteristics of those proteins were explored. Overall, the evolutionary analyses of missing-protein-encoding genes are expected to be highly instructive for proteomics and functional studies in the future. PMID- 26561871 TI - Hierarchical Surface Architecture of Plants as an Inspiration for Biomimetic Fog Collectors. AB - Fog collectors can enable us to alleviate the water crisis in certain arid regions of the world. A continuous fog-collection cycle consisting of a persistent capture of fog droplets and their fast transport to the target is a prerequisite for developing an efficient fog collector. In regard to this topic, a biological superior design has been found in the hierarchical surface architecture of barley (Hordeum vulgare) awns. We demonstrate here the highly wettable (advancing contact angle 16 degrees +/- 2.7 and receding contact angle 9 degrees +/- 2.6) barbed (barb = conical structure) awn as a model to develop optimized fog collectors with a high fog-capturing capability, an effective water transport, and above all an efficient fog collection. We compare the fog collection efficiency of the model sample with other plant samples naturally grown in foggy habitats that are supposed to be very efficient fog collectors. The model sample, consisting of dry hydrophilized awns (DH awns), is found to be about twice as efficient (fog-collection rate 563.7 +/- 23.2 MUg/cm(2) over 10 min) as any other samples investigated under controlled experimental conditions. Finally, a design based on the hierarchical surface architecture of the model sample is proposed for the development of optimized biomimetic fog collectors. PMID- 26561872 TI - Rapid Electron Beam Writing of Topologically Complex 3D Nanostructures Using Liquid Phase Precursor. AB - Advancement of focused electron beam-induced deposition (FEBID) as a versatile direct-write additive nanoscale fabrication technique has been inhibited by poor throughput, limited choice of precursors, and restrictions on possible 3D topologies. Here, we demonstrate FEBID using nanoelectrospray liquid precursor injection to grow carbon and pure metal nanostructures via direct decomposition and electrochemical reduction of the relevant precursors, achieving growth rates 10(5) times greater than those observed in standard gas-phase FEBID. Initiating growth at the free surface of a liquid pool enables fabrication of complex 3D carbon nanostructures with strong adhesion to the substrate. Deposition of silver microstructures at similar growth rates is also demonstrated as a promising avenue for future development of the technique. PMID- 26561873 TI - Asymmetric Synthesis of beta-Amino Amides by Catalytic Enantioconvergent 2-Aza Cope Rearrangement. AB - Dynamic kinetic resolutions of alpha-stereogenic-beta-formyl amides in asymmetric 2-aza-Cope rearrangements are described. Chiral phosphoric acids catalyze this rare example of a non-hydrogenative DKR of a beta-oxo acid derivative. The [3,3] rearrangement occurs with high diastereo- and enantiocontrol, forming beta-imino amides that can be deprotected to the primary beta-amino amide or reduced to the corresponding diamine. PMID- 26561875 TI - Encapsulation of Folic Acid in Zeolite Y for Controlled Release via Electric Field. AB - Zeolite Y/alginate hydrogel was used as a drug carrier/matrix for an electrophoresis transdermal drug delivery system. Folic acid (FA) as a model drug was loaded into the zeolite Y/alginate hydrogel via an ion-exchange process. The effects of cross-linking ratio, Si/Al ratio, electric field strength, and electrode polarity were investigated with respect to the release mechanism and diffusion coefficient (D) of FA using a modified Franz-diffusion cell. The FA was released from the matrix through the diffusion-controlled mechanism or Fickian diffusion because the diffusion scaling exponent value of FA was close to the value of 0.5. The D increased with an increasing cross-linking ratio and Si/Al ratio due to the mesh-size-promoting and the aluminum-content effects. The electric field strength enhanced the D of FA from the anode-FA electroreplusion. In addition, the D of FA could be varied by the electro-attractive or electro repulsive force between the positively charged FA and the charged electrode depending on whether cathode or anode was placed on the drug matrix. Thus, the fabricated zeolite/hydrogel is of great potential to be used in an electrically controlled transdermal drug delivery system where drug diffusion can be precisely activated and controlled at the time of application. PMID- 26561876 TI - Development of the knee osteoarthritis patient education questionnaire: a new measure for evaluating preoperative patient education programmes for patients undergoing total knee replacement. AB - OBJECTIVE: The aim of this study was to develop a generic instrument for the use of patients, named the Knee Osteoarthrtis Patient Education Questionnaire (KOPEQ), to assess the validity of a preoperative educational intervention and to make a preliminary test of its psychometric properties. METHODS: A patient reported outcome instrument was designed, using the conceptual framework of Wilson and Cleary as a methodological guide. Likert items with a five-point scale were chosen for the scoring option. The feasibility and interpretability of administering the KOPEQ was tested through conducting interviews with targeted patients. Items of the KOPEQ were linked to the International Classification of Functioning, Disability and Health (ICF). Psychometric testing contained internal consistency for reliability, and factor analysis for validity properties. RESULTS: A final list of 16 items was derived and linked to the ICF. Targeted patients confirmed in interviews, that all 16 questions were highly understandable and that the length of the questionnaire was feasible and acceptable. There was a good internal consistency for the 16-item KOPEQ with a Cronbach's alpha of 0.83 (95% confidence interval 0.71-0.94). Sixty-one percent of the variance was explained by a four-factor model and the factors were named "didactics", "addressability", "empowerment" and "theory". Results of a factor analysis provided a loading of the separate items between 0.469 and 0.958. CONCLUSIONS: The KOPEQ can help to provide health professionals with reliable feedback on how patients assessed the applied patient education intervention. Interviews with patients and a factor analysis revealed new and important insight. PMID- 26561877 TI - Identification and Characterization of Phytohemagglutinins from White Kidney Beans (Phaseolus vulgaris L., var. Beldia) in the Rat Small Intestine. AB - Although kidney bean (Phaseolus vulgaris L.) lectin toxicity is widely known, its effects in the gastrointestinal tract require further study. This investigation aimed to identify and characterize phytohemagglutinins (PHAs) in the small intestine and sera of rats following oral challenge with ground white beans. Twenty young, adult male rats were divided randomly into two groups of 10 animals each. The control group underwent gavage with a suspension of 300 mg of rodent pellet flour. The experimental group was administered a 300 mg Beldia bean flour suspension (BBFS). After 10 days of daily treatment, jejunal rinse liquid (JRL) and ileum rinse liquid and secretions, as well as sera, were collected. All biological fluids were screened for lectin reactivity using competitive inhibition ELISA, Ouchterlony double immunodiffusion, and immunoelectrophoresis techniques. The results revealed the presence of immunogenic intraluminal PHAs 3 4 h after the oral intake of the BBFS in the JRLs as well as in the jejunal and ileal secretions; however, no PHA was detectable in the rat sera. Ingestion of raw Beldia beans may lead to interaction between PHAs and the mucosa of the small intestine, potentially resulting in an inflammatory response. PMID- 26561878 TI - Risk of selected dermatological toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis. AB - BACKGROUND: This meta-analysis was conducted aiming at assessing the risk of selected dermatological toxicities associated with MEK inhibitors. METHODS: We considered relevant prospective randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of skin rash and acneiform dermatitis, as eligible for inclusion. RESULTS: After exclusion of ineligible studies, a total of 14 clinical trials were considered eligible for the meta-analysis. The relative risk of all grade skin rash and acneiform dermatitis was 1.71 (95% CI: 1.07-2.72; p = 0.02) and 6.55 (95% CI: 3.42-12.56; p < 0.00001), correspondingly; while the relative risk of high-grade skin rash and acneiform dermatitis was 2.64 (95% CI: 1.42 4.91; p = 0.002) and 8.44 (95% CI: 2.39-29.81; p = 0.0009), respectively. CONCLUSION: Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade skin rash and acneiform dermatitis compared with control. PMID- 26561880 TI - Introduction. PMID- 26561879 TI - Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children. AB - BACKGROUND: Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. METHODS: Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0-15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). MEASUREMENTS AND MAIN RESULTS: In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1-4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7-21.6). CONCLUSIONS: Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations. PMID- 26561881 TI - Reverberation negatively impacts musical sound quality for cochlear implant users. AB - OBJECTIVE: Satisfactory musical sound quality remains a challenge for many cochlear implant (CI) users. In particular, questionnaires completed by CI users suggest that reverberation due to room acoustics can negatively impact their music listening experience. The objective of this study was to more specifically characterize of the effect of reverberation on musical sound quality in CI users, normal hearing (NH) non-musicians, and NH musicians using a previously designed assessment method, called Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor (CI-MUSHRA). METHODS: In this method, listeners were randomly presented with an anechoic musical segment and five-versions of this segment in which increasing amounts of reverberation were artificially added. Participants listened to the six reverberation versions and provided sound quality ratings between 0 (very poor) and 100 (excellent). RESULTS: Results demonstrated that on average CI users and NH non-musicians preferred the sound quality of anechoic versions to more reverberant versions. In comparison, NH musicians could be delineated into those who preferred the sound quality of anechoic pieces and those who preferred pieces with some reverberation. DISCUSSION/CONCLUSION: This is the first study, to our knowledge, to objectively compare the effects of reverberation on musical sound quality ratings in CI users. These results suggest that musical sound quality for CI users can be improved by non-reverberant listening conditions and musical stimuli in which reverberation is removed. PMID- 26561882 TI - Cochlear implant users rely on tempo rather than on pitch information during perception of musical emotion. AB - OBJECTIVES: The purpose of this study was to investigate the extent to which cochlear implant (CI) users rely on tempo and mode in perception of musical emotion when compared with normal hearing (NH) individuals. METHODS: A test battery of novel four-bar melodies was created and adapted to four permutations with alterations of tonality (major vs. minor) and tempo (presto vs. largo), resulting in non-ambiguous (major key/fast tempo and minor key/slow tempo) and ambiguous (major key/slow tempo, and minor key/fast tempo) musical stimuli. Both CI and NH participants listened to each clip and provided emotional ratings on a Likert scale of +5 (happy) to -5 (sad). RESULTS: A three-way ANOVA demonstrated an overall effect for tempo in both groups, and an overall effect for mode in the NH group. The CI group rated stimuli of the same tempo similarly, regardless of changes in mode, whereas the NH group did not. A subgroup analysis indicated the same effects in both musician and non-musician CI users and NH listeners. DISCUSSION: The results suggest that the CI group relied more heavily on tempo than mode in making musical emotion decisions. The subgroup analysis further suggests that level of musical training did not significantly impact this finding. CONCLUSION: CI users weigh temporal cues more heavily than pitch cues in inferring musical emotion. These findings highlight the significant disadvantage of CI users in comparison with NH listeners for music perception, particularly during recognition of musical emotion, a critically important feature of music. PMID- 26561883 TI - Use of the Phantom Electrode strategy to improve bass frequency perception for music listening in cochlear implant users. AB - OBJECTIVES: The Phantom Electrode strategy makes use of partial bipolar stimulation on the two most apical electrodes in an effort to extend the frequency range available to cochlear implant (CI) users. This study aimed to quantify the effect of the Phantom Electrode strategy on bass frequency perception in music listening in CI users. METHODS: Eleven adult Advanced Bionics users with the Fidelity 120 processing strategy and 16 adult normal hearing (NH) individuals participated in the study. All subjects completed the CI-multiple stimulus with hidden reference and anchor (MUSHRA), a test of an individual's ability to make discriminations in sound quality following the removal of bass frequency information. NH participants completed the CI-MUSHRA once, whereas CI users completed the task twice - once with their baseline clinical program and once with the Phantom Electrode strategy, in random order. CI users' performance was assessed in comparison with NH performance. RESULTS: The Phantom Electrode strategy improved CI users performance on the CI-MUSHRA compared with Fidelity 120. DISCUSSION: Creation of a Phantom Electrode percept through partial bipolar stimulation of the two most apical electrodes appears to improve CI users' perception of bass frequency information in music, contributing to greater accuracy in the ability to detect alterations in musical sound quality. CONCLUSION: The Phantom Electrode processing strategy may enhance the experience of listening to music and thus acoustic stimuli more broadly by improving perception of bass frequencies, through direction of current towards the apical portion of the cochlea beyond the termination of the electrode. PMID- 26561885 TI - Developing the musical brain to boost early pre-verbal, communication and listening skills: The implications for musicality development pre- and post cochlear implantation. It is not just about Nursery Rhymes! AB - OBJECTIVES: A growing body of evidence suggests that musical activities can enhance the listening brain and develop higher cognitive functions, including linguistic abilities. The BabyBeatsTM early intervention resource, a musical habilitation resource, was designed to improve early parent interaction, early listening behaviour, early communication skills, and social and emotional development, pre- and post-implantation. METHODS: A feasibility study was conducted on families from the UK. There were two groups: seven babies <12 months old, with a varying degree of severe to profound hearing loss and eight infants who had been implanted with a cochlear implant and were now >12 months old. Audit data were collected based on a simple parental and professional feedback questionnaire, completed at the end of an 8-month trial. RESULTS: Parental feedback was positive and ideas from the resource were carried over into the family's everyday routines. Parents and professionals observed increased vocalisation, attention, and anticipation of the activities in their babies. Parents also reported increased confidence in singing, moving, and playing with their baby. CONCLUSION: These preliminary outcomes suggest that this type of intervention may lead to earlier development of communication and listening skills when used in combination with appropriate amplification. The next steps will be to include more infants, match the groups regarding age and developmental stage, to observe the infants for a longer period and to compare outcomes over time. PMID- 26561884 TI - A preliminary report of music-based training for adult cochlear implant users: Rationales and development. AB - OBJECTIVE: This paper provides a preliminary report of a music-based training program for adult cochlear implant (CI) recipients. Included in this report are descriptions of the rationale for music-based training, factors influencing program development, and the resulting program components. METHODS: Prior studies describing experience-based plasticity in response to music training, auditory training for persons with hearing impairment, and music training for CI recipients were reviewed. These sources revealed rationales for using music to enhance speech, factors associated with successful auditory training, relevant aspects of electric hearing and music perception, and extant evidence regarding limitations and advantages associated with parameters for music training with CI users. This informed the development of a computer-based music training program designed specifically for adult CI users. RESULTS: Principles and parameters for perceptual training of music, such as stimulus choice, rehabilitation approach, and motivational concerns were developed in relation to the unique auditory characteristics of adults with electric hearing. An outline of the resulting program components and the outcome measures for evaluating program effectiveness are presented. CONCLUSIONS: Music training can enhance the perceptual accuracy of music, but is also hypothesized to enhance several features of speech with similar processing requirements as music (e.g., pitch and timbre). However, additional evaluation of specific training parameters and the impact of music based training on speech perception of CI users is required. PMID- 26561886 TI - Participatory design of a music aural rehabilitation programme. AB - OBJECTIVES: Many cochlear implant (CI) users wish to enjoy music but are dissatisfied by its quality as perceived through their implant. Although there is evidence to suggest that training can improve CI users' perception and appraisal of music, availability of interactive music-based aural rehabilitation for adults is limited. In response to this need, an 'Interactive Music Awareness Programme' (IMAP) was developed with and for adult CI users. METHODS: An iterative design and evaluation approach was used. The process began with identification of user needs through consultations, followed by use of mock-up applications in workshops. Feedback from these were used to develop the prototype IMAP; a programme of 24 interactive sessions, enabling users to create and manipulate music. The prototype IMAP was subsequently evaluated in a home trial with 16 adult CI users over a period of 12 weeks. RESULTS: Overall ratings for the prototype IMAP were positive and indicated that it met users' needs. Quantitative and qualitative feedback on the sessions and software in the prototype IMAP were used to identify aspects of the programme that worked well and aspects that required improvement. The IMAP was further developed in response to users' feedback and is freely available online. CONCLUSIONS: The participatory design approach used in developing the IMAP was fundamental in ensuring its relevance, and regular feedback from end users in each phase of development proved valuable for early identification of issues. Observations and feedback from end users supported a holistic approach to music aural rehabilitation. PMID- 26561887 TI - Musical FAVORS: Reintroducing music to adult cochlear implant users. AB - Music represents a considerable challenge for many adult users of cochlear implants (CIs). Around half of adult CI users report that they do not find music enjoyable, and, in some cases, despite enhanced speech perception skills, this leads to considerable frustration and disappointment for the CI user. This paper presents suggestions to improve the musical experiences of deafened adults with CIs. Interviews with a number of adult CI users revealed that there were a number of factors which could lead to enhanced music experiences. The acronym FAVORS (familiar music, auditory-visual access, open-mindedness, and simple arrangements) summarizes the factors that have been identified, which can help CI users in their early music listening experiences. Each of these factors is discussed in detail, along with suggestions for how they can be used in therapy sessions. The use of a group approach (music focus groups) is also discussed and an overview of the approach and exercises used is presented. The importance of live music experiences is also discussed. PMID- 26561888 TI - Jumpstarting auditory learning in children with cochlear implants through music experiences. AB - Musical experiences are a valuable part of the lives of children with cochlear implants (CIs). In addition to the pleasure, relationships and emotional outlet provided by music, it serves to enhance or 'jumpstart' other auditory and cognitive skills that are critical for development and learning throughout the lifespan. Musicians have been shown to be 'better listeners' than non-musicians with regard to how they perceive and process sound. A heuristic model of music therapy is reviewed, including six modulating factors that may account for the auditory advantages demonstrated by those who participate in music therapy. The integral approach to music therapy is described along with the hybrid approach to pediatric language intervention. These approaches share the characteristics of placing high value on ecologically valid therapy experiences, i.e., engaging in 'real' music and 'real' communication. Music and language intervention techniques used by the authors are presented. It has been documented that children with CIs consistently have lower music perception scores than do their peers with normal hearing (NH). On the one hand, this finding matters a great deal because it provides parameters for setting reasonable expectations and highlights the work still required to improve signal processing with the devices so that they more accurately transmit music to CI listeners. On the other hand, the finding might not matter much if we assume that music, even in its less-than-optimal state, functions for CI children, as for NH children, as a developmental jumpstarter, a language-learning tool, a cognitive enricher, a motivator, and an attention enhancer. PMID- 26561889 TI - Using singing to nurture children's hearing? A pilot study. AB - This article reports a pilot study of the potential benefits of a sustained programme of singing activities on the musical behaviours and hearing acuity of young children with hearing impairment (HI). Twenty-nine children (n=12 HI and n=17 NH) aged between 5 and 7 years from an inner-city primary school in London participated, following appropriate ethical approval. The predominantly classroom based programme was designed by colleagues from the UCL Institute of Education and UCL Ear Institute in collaboration with a multi-arts charity Creative Futures and delivered by an experienced early years music specialist weekly across two school terms. There was a particular emphasis on building a repertoire of simple songs with actions and allied vocal exploration. Musical learning was also supported by activities that drew on visual imagery for sound and that included simple notation and physical gesture. An overall impact assessment of the pilot programme embraced pre- and post-intervention measures of pitch discrimination, speech perception in noise and singing competency. Subsequent statistical data analyses suggest that the programme had a positive impact on participant children's singing range, particularly (but not only) for HI children with hearing aids, and also in their singing skills. HI children's pitch perception also improved measurably over time. Findings imply that all children, including those with HI, can benefit from regular and sustained access to age-appropriate musical activities. PMID- 26561890 TI - Contribution of hearing aids to music perception by cochlear implant users. AB - OBJECTIVES: Modern cochlear implant (CI) encoding strategies represent the temporal envelope of sounds well but provide limited spectral information. This deficit in spectral information has been implicated as a contributing factor to difficulty with speech perception in noisy conditions, discriminating between talkers and melody recognition. One way to supplement spectral information for CI users is by fitting a hearing aid (HA) to the non-implanted ear. METHODS: In this study 14 postlingually deaf adults (half with a unilateral CI and the other half with a CI and an HA (CI + HA)) were tested on measures of music perception and familiar melody recognition. RESULTS: CI + HA listeners performed significantly better than CI-only listeners on all pitch-based music perception tasks. The CI + HA group did not perform significantly better than the CI-only group in the two tasks that relied on duration cues. Recognition of familiar melodies was significantly enhanced for the group wearing an HA in addition to their CI. This advantage in melody recognition was increased when melodic sequences were presented with the addition of harmony. CONCLUSION: These results show that, for CI recipients with aidable hearing in the non-implanted ear, using a HA in addition to their implant improves perception of musical pitch and recognition of real-world melodies. PMID- 26561891 TI - Perception of the pitch and naturalness of popular music by cochlear implant users. AB - OBJECTIVES: To assess the perceived pitch and naturalness of popular music by cochlear implant (CI) users. METHODS: Eleven experienced post-lingually deafened adult CI users rated the pitch, naturalness, and clarity of a popular song with 10 frequency allocation settings, including the default. The alternative settings all had logarithmic frequency spacing and frequency shifts of less than one octave compared with the default map. For maps which were perceived as having incorrect pitch, participants adjusted the pitch of the song in real time using a slider, in order to normalize it, and the amount of adjustment was recorded. RESULTS: The default map was rated as having close to correct pitch. Naturalness rating was negatively correlated with basal shift from a baseline logarithmic map, which was the same as the default map for basal electrodes (R(2) = 0.77). Ratings of the clarity of the lyrics were adversely affected by basal shift. The majority of participants were able to rate and adjust pitch appropriately. The frequency shift in the map was highly correlated with participants' adjustments of the pitch slider (R(2) = 0.94), but the adjustments were less than expected for the majority of participants. DISCUSSION: The pitch ratings for the default allocation suggest that participants have acclimatized to their processors' frequency allocations. Adjustment of the pitch of the song was possible for the majority and suggested that all but one participant was experiencing frequency compression. Expansion of the frequency allocation might help to alleviate this. CONCLUSION: Adjustment of the pitch of a popular song could be helpful for tuning CIs. PMID- 26561892 TI - Pitch and lexical tone perception of bilingual English-Mandarin-speaking cochlear implant recipients, hearing aid users, and normally hearing listeners. AB - OBJECTIVES: The purpose of this current study was to investigate whether pitch, lexical tone, and/or speech-in-noise perception were significantly correlated for Singaporean teenagers or adults who spoke both Mandarin and English. METHODS: Thirty-three normal hearing or near-normal hearing listeners who did not use a hearing device (NNH group), eight postlingually deafened cochlear implant (CI) recipients (CI group), and three postlingually deafened bilateral hearing aid (HA) users (HA group) were recruited. All participants were bilingual Mandarin English-speaking Singaporean residents. Participants were assessed on tests of pitch-ranking, lexical tone perception, and speech-in-noise. RESULTS: The NNH group scored significantly better than the CI group for all tests and subtests. There were no significant differences for the pitch test between the HA group and either the CI or NNH group. However, HA users scored significantly better than the CI group, and more aligned with the NNH group's scores for both the lexical tone and Mandarin speech-in-noise test. There were highly significant moderate positive correlations between all three tests. Discussion Overall, the performance of the CI users in this study indicates that CI recipients still struggle on pitch-related auditory perception tasks. Additionally, although the test scores from the HA users were better than the CI recipients, they were not as good as the NNH listeners. The significant moderate correlations between all three tests indicate that there is at least some degree of overlap in the skills required to accurately perceive these stimuli. CONCLUSION: The overall results suggest that CI users, and to a lesser extent HA users, still struggle with complex auditory perceptual tasks, particularly when it requires the perception of pitch. However, it may be possible that training one of these skills (e.g. musical pitch) may then generalize to other tasks (e.g. lexical tone and/or speech-in-noise). This is important for counseling, as well as for planning effective rehabilitation programs. PMID- 26561894 TI - Routine integration of palliative care: what will it take? PMID- 26561896 TI - Correction. PMID- 26561895 TI - Reassessing rare cancers. PMID- 26561897 TI - The challenges of early diagnosis of cancer in general practice. PMID- 26561899 TI - Climate change is harmful to our health: taking action will have many benefits. PMID- 26561898 TI - Advances in radiation therapy. PMID- 26561900 TI - Legionella pneumonia with severe rhabdomyolysis. PMID- 26561901 TI - Can patients presenting with acute coronary syndrome be screened for diabetes using glycosylated haemoglobin? PMID- 26561902 TI - Exploring the value of interprofessional student-led clinics for chronic disease patients. PMID- 26561903 TI - Indigenous health expenditure deficits obscured in Closing the Gap reports. PMID- 26561904 TI - Life expectancy discussions in a multisite sample of Australian medical oncology outpatients. AB - OBJECTIVES: The study examined: 1) the proportion of patients who received their preferred level of information about life expectancy; and 2) sociodemographic, clinical and psychological factors associated with patients' perceptions of whether they received too little, too much, or the right amount of information about life expectancy. DESIGN: Cross-sectional survey. SETTING: Eleven large Australian medical oncology treatment centres. PARTICIPANTS: A total of 1431 medical oncology outpatients participated (81% consent rate). Eligible patients were approached between September 2012 and May 2014. MAIN OUTCOME MEASURES: Patients indicated whether the information about life expectancy they received aligned with their preferences. RESULTS: Almost one in four patients (24%) received too little information, 4% received too much, and 50% received all the information they wanted; 22% of patients neither wanted nor received information about life expectancy. Patients were more likely to receive too little information if they were not in remission (odds ratio [OR], 1.77), did not know their cancer stage at diagnosis (OR, 3.64), or were anxious (OR, 1.48) or depressed (OR, 1.48). Patients had greater odds of receiving too much information if they were younger (OR, 1.45), had more advanced cancer (OR, 2.01) or did not know their cancer stage at diagnosis (OR, 4.42). CONCLUSIONS: That fact that 28% of cancer patients did not receive their desired level of information about life expectancy highlights the difficulties associated with discussing this sensitive topic. To ensure that life expectancy discussions correspond with patient preferences, clinicians should routinely ask patients whether they want to know this information, in what format, and at which level of detail. PMID- 26561905 TI - Do teleoncology models of care enable safe delivery of chemotherapy in rural towns? AB - OBJECTIVES: To compare the dose intensity and toxicity profiles for patients undergoing chemotherapy at the Townsville Cancer Centre (TCC), a tertiary cancer centre in northern Queensland, with those for patients treated in Mount Isa, supervised by the same medical oncologists via teleoncology. DESIGN: A quasi experimental design comparing two patient groups. SETTING: TCC and Mount Isa Hospital, which both operate under the auspices of the Townsville Teleoncology Network (TTN). PARTICIPANTS: Eligible patients who received chemotherapy at TCC or Mt Isa Hospital between 1 May 2007 and 30 April 2012. INTERVENTION: Teleoncology model for managing cancer patients in rural towns. MAIN OUTCOME MEASURES: Dose intensity (doses, number of cycles and lines of treatment) and toxicity rates (rate of serious side effects, hospital admissions and mortality). RESULTS: Over 5 years, 89 patients received a total of 626 cycles of various chemotherapy regimens in Mount Isa. During the same period, 117 patients who received a total of 799 cycles of chemotherapy at TCC were eligible for inclusion in the comparison group. There were no significant differences between the Mount Isa and TCC patients in most demographic characteristics, mean numbers of treatment cycles, dose intensities, proportions of side effects, and hospital admissions. There were no toxicity-related deaths in either group. CONCLUSION: It appears safe to administer chemotherapy in rural towns under the supervision of medical oncologists from larger centres via teleoncology, provided that rural health care resources and governance arrangements are adequate. PMID- 26561907 TI - Disseminated methicillin-sensitive Staphylococcus aureus infection resulting from a paracervical abscess after acupuncture. PMID- 26561906 TI - General practitioners' prescribing of lipid-lowering medications for Indigenous and non-Indigenous Australians, 2001-2013. AB - OBJECTIVE: To examine the prescribing of lipid-lowering medications during general practitioner encounters with Indigenous and non-Indigenous Australians from 2001 to 2013. DESIGN, SETTING AND PARTICIPANTS: Observational time trend study, using data from the Bettering the Evaluation and Care of Health (BEACH) survey, of 9594 primary care encounters with Indigenous patients and 750 079 encounters with non-Indigenous patients aged 30 years or over. MAIN OUTCOME MEASURE: Prescription of at least one lipid-lowering medication. RESULTS: The age sex standardised proportion of encounters that resulted in at least one lipid lowering medication being prescribed was 5.5% (95% CI, 4.7%-6.3%) for Indigenous patients and 4.6% (95% CI, 4.5%-4.7%) for non-Indigenous patients. The proportion of encounters with Indigenous patients at which a lipid-lowering medication was prescribed increased significantly from 4.1% during 2001-2005 to 6.4% during 2009 2013 (P = 0.013 for trend). For encounters with non-Indigenous patients, the proportion increased significantly from 3.8% during 2001-2005 to 5.2% during 2009 2013 (P < 0.01). For encounters during which GPs managed diabetes, hypertension or ischaemic heart disease, the proportion of Indigenous encounters during which lipid-lowering medication was prescribed was similar to that for non-Indigenous patients. For encounters in which GPs managed a lipid disorder, however, the age sex standardised proportion was significantly greater for Indigenous (78.4%; 95% CI, 72.6%-84.2%) than for non-Indigenous patients (65.2%; 95% CI, 64.5%-65.8%). CONCLUSION: We detected substantial increases in the prescribing of lipid lowering medications from 2001 to 2013 for both Indigenous and non-Indigenous patients seen in Australian general practice. Providers were more likely to prescribe lipid-lowering medications for Indigenous than for non-Indigenous patients, suggesting some measure of success in expanding access to medications and reducing cardiovascular risk among Indigenous people. PMID- 26561908 TI - Malnutrition: a global health perspective from a Timorese mountain. PMID- 26561909 TI - Upstream or downstream? PMID- 26561911 TI - Empowering clinicians to address the global challenge of trauma: an example from Myanmar. PMID- 26561912 TI - Comb sign in intestinal obstruction secondary to desmoplastic reaction due to an ileal neuroendocrine tumor. AB - This article report the case of an intestinal obstruction secondary to desmoplastic reaction of an ileum neuroendocrine tumor (NET), that was radiologically diagnosed by the comb sign. This is an infrequent clinical manifestation of NETs, often underdiagnosed, related to local overproduction of serotonin. PMID- 26561913 TI - Direct parasitologial diagnosis of infection with Hysterothylacium aduncum in a patient with epigastralgia. AB - Anisakis parasitization has been on the rise because some factors, like increased interest in dishes consisting of raw fish. We report a case of epigastralgia with direct diagnosis by endoscopy, which futher study pointed out H. Aduncum as causal agent, a anisakis which is rarely involved in human anisakiasis. PMID- 26561914 TI - Automated measurement of CT noise in patient images with a novel structure coherence feature. AB - While the assessment of CT noise constitutes an important task for the optimization of scan protocols in clinical routine, the majority of noise measurements in practice still rely on manual operation, hence limiting their efficiency and reliability. This study presents an algorithm for the automated measurement of CT noise in patient images with a novel structure coherence feature. The proposed algorithm consists of a four-step procedure including subcutaneous fat tissue selection, the calculation of structure coherence feature, the determination of homogeneous ROIs, and the estimation of the average noise level. In an evaluation with 94 CT scans (16 517 images) of pediatric and adult patients along with the participation of two radiologists, ROIs were placed on a homogeneous fat region at 99.46% accuracy, and the agreement of the automated noise measurements with the radiologists' reference noise measurements (PCC = 0.86) was substantially higher than the within and between-rater agreements of noise measurements (PCCwithin = 0.75, PCCbetween = 0.70). In addition, the absolute noise level measurements matched closely the theoretical noise levels generated by a reduced-dose simulation technique. Our proposed algorithm has the potential to be used for examining the appropriateness of radiation dose and the image quality of CT protocols for research purposes as well as clinical routine. PMID- 26561915 TI - Non-anesthesiologist administration of propofol for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates Guideline--Updated June 2015. PMID- 26561916 TI - Efficacy and safety of bovine activated factors IIa/VIIa/IXa/Xa in patients with active gastrointestinal bleeding: a proof of concept study. AB - BACKGROUND AND STUDY AIMS: Endoscopic treatment of active gastrointestinal bleeding often remains difficult, and considerable technical expertise is required. Our aim was to assess the efficacy and safety of endoscopic hemostasis with a liquid combination of bovine activated factors IIa/VIIa/IXa/Xa (SeraSeal). METHODS: Patients with active gastrointestinal bleeding were prospectively included. In group A, 5 mL of bovine activated factors IIa/VIIa/IXa/Xa was topically applied via catheters to the bleeding site as initial hemostasis; group B received a similar application but as rescue therapy after failure of conventional endoscopic hemostasis. RESULTS: In group A, bleeding was stopped by the agent in 15 /22 patients (68 %) and by conventional endoscopic hemostasis in 5 of the other 7, with coiling and surgery required for definitive hemostasis in 2. In group B, the addition of the agent definitively stopped bleeding in 13 /15 patients (87 %), with hemostasis in the remaining 2 achieved with fibrin glue. Rebleeding was observed in 1 patient. CONCLUSIONS: Our proof of concept study suggests that the use of bovine activated factors IIa/VIIa/IXa/Xa might be a safe and effective addition to current endoscopic hemostatic strategies, but further studies are necessary.ClinicalTrials.gov identifier: NCT02349490. PMID- 26561917 TI - A meta-analysis comparing ProCore and standard fine-needle aspiration needles for endoscopic ultrasound-guided tissue acquisition. AB - BACKGROUND AND STUDY AIMS: To overcome the limitations associated with cytology, a uniquely designed needle (ProCore) was introduced in an effort to obtain a core of tissue under endoscopic ultrasound (EUS) guidance. However, studies comparing the sample quality between ProCore and standard-design fine-needle aspiration (FNA) needles have yielded varying results. A systematic review and meta-analysis was therefore conducted to compare the performance of the ProCore and standard FNA needles when performing EUS-guided tissue acquisition. PATIENTS AND METHODS: MEDLINE and EMBASE were searched to identify all published manuscripts that compared the ProCore needle with standard FNA needles. Noncomparative and technical feasibility studies were excluded. The main outcome measures were diagnostic adequacy, diagnostic accuracy, acquisition of histological core tissue, and mean number of passes required to achieve a diagnosis when sampling solid lesions. RESULTS: Nine studies (total 576 patients) met the inclusion criteria. There was no significant difference in diagnostic adequacy (75.2 % vs. 89.0 %, odds ratio [OR] 0.39, P = 0.23), diagnostic accuracy (85.8 % vs. 86.2 %, OR 0.88, P = 0.53) or rate of histological core specimen acquisition (77.7 % vs. 76.5 %, OR 0.94, P = 0.85) between the ProCore and standard FNA needles, respectively. The mean number of passes required for diagnosis, however, was significantly lower when using the ProCore needle (standardized mean difference - 1.2, P < 0.001). CONCLUSIONS: Current data do not demonstrate a significant difference between the ProCore and standard FNA needles for sample adequacy, diagnostic accuracy or acquisition of a core specimen. However, the ProCore needle establishes the diagnosis with fewer passes. PMID- 26561918 TI - Use of patency capsule in patients with established Crohn's disease. AB - BACKGROUND AND STUDY AIMS: Video capsule endoscopy (VCE) is invaluable in the diagnosis of small-bowel pathology. Capsule retention is a major concern in patients with Crohn's disease. The patency capsule was designed to evaluate small bowel patency before VCE. However, the actual benefit of the patency capsule test in Crohn's disease remains unclear. The aim of this study was to evaluate the clinical impact of patency capsule use on the risk of video capsule retention in patients with established Crohn's disease. PATIENTS AND METHODS: This was a retrospective, multicenter study of patients with established Crohn's disease who underwent VCE for clinical need. The utilization strategy for the patency capsule was classified as selective (only in patients with obstructive symptoms, history of intestinal obstruction or surgery, or per treating physician's request) or nonselective (all patients with Crohn's disease). The main outcome was video capsule retention in the entire cohort and within each utilization strategy. RESULTS: A total of 406 patients who were referred for VCE were included in the study. VCE was performed in 132 /406 patients (32.5 %) without a prior patency capsule test. The patency capsule test was performed in 274 /406 patients (67.5 %) and was negative in 193 patients. Overall, VCE was performed in 343 patients and was retained in the small bowel in 8 (2.3 %). In this cohort, the risk of video capsule retention in the small bowel was 1.5 % without use of a prior patency capsule and 2.1 % after a negative patency test (P = 0.9). A total of 18 patients underwent VCE after a positive patency capsule test, with a retention rate of 11.1 % (P = 0.01). Patency capsule administration strategy (selective vs. nonselective) was not associated with the risk of video capsule retention. CONCLUSIONS: Capsule retention is a rare event in patients with established Crohn's disease undergoing VCE. The risk of video capsule retention was not reduced by the nonselective use of the patency capsule. Furthermore, VCE after a positive patency capsule test in patients with Crohn's disease was associated with a high risk of video capsule retention. PMID- 26561920 TI - Coupled phase field, heat conduction, and elastodynamic simulations of kinetic superheating and nanoscale melting of aluminum nanolayer irradiated by picosecond laser. AB - An advanced continuum model for nanoscale melting and kinetic superheating of an aluminum nanolayer irradiated by a picosecond laser is formulated. Barrierless nucleation of surface premelting and melting occurs, followed by a propagation of two solid-melt interfaces toward each other and their collision. For a slow heating rate of Q = 0.015 K ps(-1) melting occurs at the equilibrium melting temperature under uniaxial strain conditions T = 898.1 K (i.e., below equilibrium melting temperature Teq = 933.67 K) and corresponding biaxial stresses, which relax during melting. For a high heating rate of Q = 0.99-84 K ps(-1), melting occurs significantly above Teq. Surprisingly, an increase in heating rate leads to temperature reduction at the 3 nm wide moving interfaces due to fast absorption of the heat of fusion. A significant, rapid temperature drop (100-500 K, even below melting temperature) at the very end of melting is revealed, which is caused by the collision of two finite-width interfaces and accelerated melting in about the 5 nm zone. For Q = 25-84 K ps(-1), standing elastic stress waves are observed in a solid with nodal points at the moving solid-melt interfaces, which, however, do not have a profound effect on melting time or temperatures. When surface melting is suppressed, barrierless bulk melting occurs in the entire sample, and elastodynamic effects are more important. Good correspondence with published, experimentally-determined melting time is found for a broad range of heating rates. Similar approaches can be applied to study various phase transformations in different materials and nanostructures under high heating rates. PMID- 26561919 TI - Contrast-enhanced harmonic endoscopic ultrasonography with time-intensity curve analysis for intraductal papillary mucinous neoplasms of the pancreas. AB - BACKGROUND AND STUDY AIMS: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. PATIENTS AND METHODS: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. RESULTS: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). CONCLUSIONS: CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD. PMID- 26561921 TI - Transient electrochemistry: beyond simply temporal resolution. AB - Some physicochemical intrigues for which transient electrochemistry was necessary to solve the problem are summarized in this feature article. First, we highlight the main constraints to be aware of to access to low time scales, and particularly focus on the effects of stray capacitances. Then, the electron transfer rate constant measured for redox molecules in a self-assembled monolayer configuration is compared to the conductance measured through the same systems, but at the single molecule level. This evidences strong conformational changes when molecules are trapped in the nanogap created between both electrodes. We also report about dendrimers, for which a short electrochemical perturbation induces creation of a diffusion layer within the molecule, allowing the electron hopping rate to be measured and analyzed in terms of molecular motions of the redox centers. Finally, we show that transient electrochemistry provides also useful information when coupled to other methodologies. For example, when an ultrasonic field drives very fast movements of a bubble situated above the electrode surface, the motion can be detected indirectly through a modification of the diffusion flux. Another field concerns pulse radiolysis, and we describe how the reactivity (at the electrode or within the solution) of radicals created by a radiolytic pulse can be quantified, widening the possibilities of electrochemistry to operate in biological media. PMID- 26561922 TI - PD-L1 Expression as a Predictive Biomarker: Is Absence of Proof the Same as Proof of Absence? PMID- 26561923 TI - Characteristics of patients with benign partial epilepsy in infancy without PRRT2 mutations. AB - Mutations in the proline-rich transmembrane protein 2 gene (PRRT2) are known to cause clinical symptoms of paroxysmal kinesigenic dyskinesia (PKD), benign partial epilepsy in infancy (BPEI), and infantile convulsions with choreoathetosis (ICCA) syndrome; however, not all patients with BPEI have PRRT2 mutations, and the genetic backgrounds for such patients are still unknown. To characterize BPEI patients without PRRT2 mutations, we analyzed unrelated 63 patients with BPEI. Sanger sequencing identified PRRT2 mutations in 33 probands (52%). The most common insertion, c.649dup, was identified in 28 probands. Two novel truncation mutations, c.232dup and c.503_504del were identified independently. 16p11.2 microdeletion was not detected in patients without PRRT2 mutations. PRRT2 mutation detection rates were 21/31 (68%) and 12/32 (38%) in probands who were positive or negative for family history, respectively, indicating a significant difference between the two groups. In this study, 20 probands with BPEI were negative for family history of BPEI and negative for PRRT2 mutation. BPEI in these probands may be due to complex genetic predispositions. Because the possibility remains that a second gene contributes to BPEI, further studies are necessary in patients with BPEI but no PRRT2 mutation, especially in Asian people. PMID- 26561924 TI - Asymmetry in cross-hippocampal connectivity in unilateral mesial temporal lobe epilepsy. AB - Mesial temporal lobe epilepsy (mTLE) is mostly characterized by hippocampal sclerosis (HS) changes. Although considerable progress has been made in understanding the altered functional network of mTLE patients, whether one side of the abnormal hippocampal (HP) structure will affect the other healthy side of the hippocampal network is still unclear. Here, we used a seed-based method to explore the commonly alterative hippocampal network in mTLE patients by comparing the bilateral hippocampal network of unilateral mTLE patients with healthy control participants. We observed that both sides of the hippocampal network in unilateral mTLE patients were changed independent of the affected or "healthy" side, which may suggest a common plasticity network for both sides of hippocampal sclerosis mesial temporal lobe epilepsy patients. Furthermore, using the HP as the ROI, we found that the functional connectivity of the intra-HP in the left mTLE-HS group was moderately positively correlated with the duration of the disease, while a strong negative correlation between functional connectivity of the intra-HP and duration were detected in the right mTLE-HS group, which suggested that it was easier for the right HP than the left HP to communicate with the contralateral HP according to the progression of mTLE disease because the hippocampus plays different roles in the communication and compensatory mechanism associated with the contralateral side of the hemisphere. We hope that this potential relevance may help us to better characterize mTLE with hippocampal sclerosis and ultimately assist in providing a better diagnosis and more accurate invasive treatments of mTLE. PMID- 26561926 TI - Five-year clinical outcome of posterior zirconia ceramic inlay-retained FDPs with a modified design. AB - OBJECTIVES: To evaluate the 5-year clinical outcome of posterior inlay-retained fixed dental prostheses (IRFDPs) with a modified design made from zirconia ceramic (Vita In-Ceram YZ, Vita Zahnfabrik, Bad Sackingen, Germany). METHODS: Thirty 3-unit IRFDPs were placed in 30 patients. Seven IRFDPs replaced the second premolars (4 in the maxilla, 3 in the mandible), and 23 replaced the first molars (15 in the maxilla, 8 in the mandible). Preparations were performed in accordance with general principles for ceramic inlay restorations and modified with a short retainer-wing bevel preparation within the enamel at the buccal and oral sides. The frameworks were milled from zirconia ceramic, and the pontics were veneered with feldspathic ceramic. After air-abrasion of bonding surfaces, IRFDPs were bonded with an adhesive composite resin. The patients were recalled 6-12 months after placement, and then annually. Kaplan-Meier analysis was used to calculate the survival and complication rates of the IRFDPs. RESULTS: After a mean observation time of 64.4 (SD=17.6) months (min 15, max 95.6), the 5-year cumulative survival of IRFDPs was 95.8%. Debonding was reported for two IRFDPs (6.9%), one of them failed finally after 49.4 months due to repeated debonding. Chipping of the veneering ceramic was reported in three cases (10.5%). Secondary caries were reported in 2 patients (8.1%). Nevertheless, the latter complications did not affect the clinical function of the involved IRFDPs. CONCLUSION: The 5 year clinical outcome of zirconia-based IRFDPs fabricated in the modified design is encouraging, so that they may represent a treatment alternative to replace posterior single missing teeth, taking into consideration the appropriate case selection. PMID- 26561925 TI - Biological variations of thirteen plasma biochemical indicators. AB - BACKGROUND: Reports on biological variation of plasma biochemical indicators are limited. We evaluated biological variations of 13 plasma biochemical indicators. METHODS: Plasma samples were collected from 40 healthy individuals over 5days. Intra-individual coefficient of variation (CVI), inter-individual coefficient of variation (CVG), index of individuality (II), reference change value (RCV), and analytical goal parameters were calculated. RESULTS: Albumin (Alb) showed the lowest CVI (2.50%) and the lowest CVG (5.08%), while C-reactive protein (hsCRP) presented the highest CVI (26.87%) and CVG (61.73%). II values were all less than 1.0. Alb presented the lowest 95% RCV (7.67), while hsCRP showed the highest 95% RCV (74.61). Alb, urea, creatinine (Cr), creatine kinase (CK), and creatine kinase isoenzyme MB (CKMBmass) CVI differed with gender (P<0.05). The CVG of the 13 indicators presented a significant gender difference (P<0.0001). Alb showed the lowest desirable imprecision CV (1.3%), the lowest desirable bias (1.4%), and the lowest desirable total error (3.5%), while hsCRP presented the highest desirable imprecision (13.4%), the highest desirable bias (16.8%), and the highest desirable total error (39.0%). CONCLUSION: Our findings add to the database of biological variations of plasma indicators. PMID- 26561927 TI - Dysphagia Following Airway Reconstruction in Adults. AB - IMPORTANCE: Patients who undergo open airway reconstruction procedures are likely to experience some degree of postoperative dysphagia symptoms and delayed return to oral intake. OBJECTIVE: To review the duration of postoperative dysphagia symptoms and outcomes in a group of adult patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the medical records of adult patients undergoing laryngotracheoplasty, posterior cricoid split laryngoplasty, tracheal resection, and cricotracheal resection in a tertiary hospital between July 2009 and September 2014. EXPOSURES: Laryngotracheoplasty, posterior cricoid split laryngoplasty, tracheal resection, and cricotracheal resection. MAIN OUTCOMES AND MEASURES: Demographic characteristics, etiology of airway stenosis, surgical procedure, stent type, and duration of dysphagia symptoms. RESULTS: Thirty-eight patients (14 men, 24 women; mean [SD; range] age, 48 [14.4; 20-80] years) fitting the inclusion criteria were identified. Twenty-four (63%) patients had laryngotracheal stenosis secondary to prolonged intubation, with 3 (8%), 5 (13%), and 6 (16%) cases being due to autoimmune, idiopathic, or other etiology, respectively. Twenty-five (66%) patients underwent tracheal or cricotracheal resection, and 13 (34%) underwent laryngotracheoplasty or posterior cricoid split laryngoplasty. Of the 17 patients with stents placed, 6 (35%) patients had a suprastomal stent sewn at the top with a polypropylene suture using a horizontal mattress technique, 6 (35%) patients had a suprastomal stent capped with an extended Silastic thoracic T-tube segment, and 5 (29%) patients had either a T tube or hood bronchial stent. Eight of 17 patients used a nasogastric feeding tube while the stent was in place (up to 5 weeks). All patients returned to their preoperative diet. The mean (SD) duration of dysphagia symptoms in all patients (both those without a stent and following stent removal) was 8 (27.2) days (median, 1.5 days). The mean (SD) duration of dysphagia symptoms in patients who did not have a stent placed was 4.8 (5.3) days (median, 4 days). CONCLUSIONS AND RELEVANCE: In this study of adults who underwent open airway reconstruction, all returned to their preoperative diet, but those without stents had a shorter duration of dysphagia symptoms than those with stents. Approximately half as many patients with a stent had a prolonged course with dysphagia symptoms compared with those without a stent. PMID- 26561929 TI - Detection and analysis of nanoparticles in patients: A critical review of the status quo of clinical nanotoxicology. AB - On the cusp of massive commercialization of nanotechnology-enhanced products and services, the physical and chemical analysis of nanoparticles in human specimens merits immediate attention from the research community as a prerequisite for a confident clinical interpretation of their occurrence in the human organism. In this review, we describe the caveats in current practices of extracting and isolating nanoparticles from clinical samples and show that they do not help truly define the clinical significance of detected exogenous nano-sized objects. Finally, we suggest a systematic way of tackling these demanding scientific tasks. More specifically, a precise and true qualitative evaluation of nanoparticles in human biological samples is still hindered by various technical reasons. Such a procedure is more refined when the nature of the pollutants is known, like in the case of nano-sized wear debris originating from biomedical prostheses. Nevertheless, nearly all available analytical methods provide unknown quantitative accuracy and qualitative precision due to the challenging physical and chemical nature of nanoparticles. Without trustworthy information to describe the nanoparticulate load of clinical samples, it is impossible to accurately assess its pathological impact on isolated cases or allow for relevant epidemiological surveys on large populations. Therefore, we suggest that the many and various specimens stored in hospitals be used for the refinement of methods of exhaustive quantitative and qualitative characterization of prominent nanoparticles in complex human milieu. PMID- 26561928 TI - Anti-inflammatory effects of the extract of Gnaphalium affine D. Don in vivo and in vitro. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Gnaphalium affine D. Don (GA) has been traditionally used as a medicinal herb in China for the treatment of many ailments including rheumatoid arthritis. However, the anti-arthritic mechanism of GA has still not been demonstrated. This study aims to reveal the anti inflammatory activity and anti-arthritic mechanism of ethanol extract of G. affine D. Don. MATERIALS AND METHODS: Anti-inflammatory potential of GA was analyzed in vivo in carrageenan induced mice paw edema (acute study). Also, in vivo study was applied in collagen-induced arthritis (CIA) rats. In vitro experiments for analyzing the anti-inflammatory potential of GA were performed on rat alveolar macrophages cell line (NR8383). Analysis of nitric oxide release in NR8383 cells was done by Griess reaction. RT-PCR and western blotting experiment was performed to analyze the expression of phosphorylated p65 and IkappaBalpha/beta-actin in NF-kappaB pathway. The production of TNF-alpha, IL 1beta, and COX-2 in NR8383 cells were measured by enzyme-linked immunosorbent assay. The chemical profile of GA was analyzed by HPLC-VWD. RESULTS: GA significantly reduced the paw volume in carrageenan induced rat paw edema rat at different doses (300 and 600 mg/kg), compared with the standard indomethacin treatment. In CIA, GA can obviously ameliorate the inflammatory symptom, including cytokine, histological symptom and paw swelling. In the vitro study, GA was able to reduce the nitric oxide (NO) levels in NR8383 cells that had been stimulated with lipopolysaccharide (LPS). The level of TNF-alpha, IL-1beta, and COX-2 was also decreased with GA treatment in NR8383 cells that had been stimulated with lipopolysaccharide (LPS). Interestingly, GA was found to decrease the level of phosphorylated p65 and IkappaBalpha in NR8383 cells. Fifteen compounds were identified by HPLC-VWD with the reference substances and verified by LC-MS. CONCLUSIONS: The results of the experiment scientifically validated its traditional use in inflammatory conditions. PMID- 26561930 TI - In vitro and in vivo evaluation of a new zirconia/niobium biocermet for hard tissue replacement. AB - Metals and ceramics are commonly used in orthopaedics, dentistry and other load bearing applications. However, the use of ceramic matrix composites reinforced with biocompatible metals for heavy load-bearing hard tissue replacement applications has not previously been reported. In order to improve the reliability and the mechanical properties of biomedical implants, new zirconia-Nb composites have been recently developed. The aim of this study was to investigate the biological tolerance of these new zirconia/Nb biocermets implants with both in vitro and in vivo approaches. At first, human bone marrow derived mesenchymal stem cells were cultured on sintered biocermet discs with polished surfaces and were compared with responses to niobium metal. In vitro, the biocermets showed no deleterious effect on cell proliferation, extra-cellular matrix production or on cell morphology. Furthermore, the biocermet showed a higher percentage of cell proliferation than Nb metal. On the other hand, the bone response to these new zirconia/Nb biocermets was studied. Cylinders of biocermets, as well as commercially Nb rod were implanted in the tibiae of New Zealand white rabbits. All the animals were euthanatized after 6 months. The specimens were processed to obtain thin ground sections. The slides were observed in normal transmitted light microscope. A newly formed bone was observed in close contact with material surfaces. No inflamed or multinucleated cells were present. This study concluded that zirconia/Nb composites are biocompatible and osteoconductive. The ceramic metal composite has even better osteointegration ability than pure Nb. In conclusion, zirconia-Nb biocermet is suitable for heavy load-bearing hard tissue replacement from the point of view of both mechanical properties and biocompatibility. PMID- 26561931 TI - Current advances and future perspectives in extrusion-based bioprinting. AB - Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. PMID- 26561932 TI - Successful endothelialization and remodeling of a cell-free small-diameter arterial graft in a large animal model. AB - The large number of coronary artery bypass procedures necessitates development of off-the-shelf vascular grafts that do not require cell or tissue harvest from patients. However, immediate thrombus formation after implantation due to the absence of a healthy endothelium is very likely. Here we present the successful development of an acellular tissue engineered vessel (A-TEV) based on small intestinal submucosa that was functionalized sequentially with heparin and VEGF. A-TEVs were implanted into the carotid artery of an ovine model demonstrating high patency rates and significant host cell infiltration as early as one week post-implantation. At one month, a confluent and functional endothelium was present and the vascular wall showed significant infiltration of host smooth muscle cells exhibiting vascular contractility in response to vaso-agonists. After three months, the endothelium aligned in the direction of flow and the medial layer comprised of circumferentially aligned smooth muscle cells. A-TEVs demonstrated high elastin and collagen content as well as impressive mechanical properties and vascular contractility comparable to native arteries. This is the first demonstration of successful endothelialization, remodeling, and development of vascular function of a cell-free vascular graft that was implanted in the arterial circulation of a pre-clinical animal model. PMID- 26561933 TI - Hybrid small-diameter vascular grafts: Anti-expansion effect of electrospun poly epsilon-caprolactone on heparin-coated decellularized matrices. AB - Small-diameter vascular grafts (SDVGs) (D < 6 mm) are increasingly needed in clinical settings for cardiovascular disease, including coronary artery and peripheral vascular pathologies. Vessels made from synthetic polymers have shortcomings such as thrombosis, intimal hyperplasia, calcification, chronic inflammation and no growth potential. Decellularized xenografts are commonly used as a tissue-engineering substitute for vascular reconstructive procedures. Although acellular allogeneic vascular grafts have good histocompatibility and antithrombotic properties, the decellularization process may damage the biomechanics and accelerate the elastin deformation and degradation, finally resulting in vascular graft expansion and even aneurysm formation. Here, to address these problems, we combine synthetic polymers with natural decellularized small-diameter vessels to fabricate hybrid tissue-engineered vascular grafts (HTEV). The donor aortic vessels were decellularized with a combination of different detergents and dehydrated under a vacuum freeze-drying process. Polycaprolactone (PCL) nanofibers were electrospun (ES) outside the acellular aortic vascular grafts to strengthen the decellularized matrix. The intimal surfaces of the hybrid small-diameter vascular grafts were coated with heparin before the allograft transplantation. Histopathology and scanning electron microscope revealed that the media of the decellularized vessels were severely injured. Mechanical testing of scaffolds showed that ES-PCL significantly enhanced the biomechanics of decellularized vessels. Vascular ultrasound and micro-CT angiography showed that all grafts after implantation in a rat model were satisfactorily patent for up to 6 weeks. ES-PCL successfully prevented the occurrence of vasodilation and aneurysm formation after transplantation and reduced the cell inflammatory infiltration. In conclusion, the HTEV with perfect histocompatibility and biomechanics provide a facile and useful technique for the development of SDVGs. PMID- 26561934 TI - Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation? AB - The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. PMID- 26561935 TI - Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: A mouse femoral segmental defect study. AB - Treatment of complex bone defects places a significant burden on the US health care system. Current strategies for treatment include grafting and stabilization using internal metal plates/screws, intramedullary rods, or external fixators. Here, we introduce the use of shape memory polymer (SMP) materials for grafting and adjunct stabilization of segmental defects. Self-deploying SMP grafts and SMP sleeves capable of expanding and contracting, respectively, under intraoperative conditions were developed and evaluated in a mouse segmental defect model in vivo. Integration between grafts/sleeves and native bone was assessed using x-ray radiography, microcomputed tomography, and torsional mechanical testing. We found that SMP grafts were able to integrate with the native bone after 12 weeks, maintain defect stability, and provide torsional mechanical properties comparable to an allograft alone treatment; however no gross de novo bone formation was observed. SMP sleeves did not inhibit bony bridging at the margins, and limbs treated with a sleeve/allograft combination had torsional mechanical properties comparable to limbs treated with an allograft alone. In vitro torsional and bending tests suggest sleeves may provide additional torsional stability to defects. Incorporation of shape memory into synthetic bone graft substitutes and adjunct stabilization devices is anticipated to enhance functionality of synthetic materials employed in both applications. PMID- 26561936 TI - Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs. AB - To achieve active tumor targeting and sequential release of 3 drugs to a tumor site in one nanoparticulate system, self-decomposable SiO2 nanoparticles modified by 3-aminopropyltriethoxysilane (APTS) as their inner structure were used to double load HCPT (in the NP core) and Dox (on the NP surface). Meanwhile, monoclonal antibodies (mAb198.3) against the FAT1 antigen and Bcl-2 siRNA were conjugated onto PEGylated Au-PEG-COOH nanoparticles. The obtained drug-loaded SiO2 nanoparticles were coated with the Au-PEG-mAb.198.3/siRNA nanoparticles through electrostatic interaction to form the SiO2@AuNP sequential drug delivery system, which featured the controlled and sequential release of siRNA, Dox and HCPT step by step to maximize its anticancer efficacy. The results revealed that the SiO2@AuNP sequential drug delivery system specifically targeted tumor cells and was internalize rapidly, followed by endosome escape and sequential drug release. Importantly, the sustainable release characteristics of SiO2 made the Tmax difference between HCPT and Dox approximately 8-12 h, and this enhanced the sensitizing efficiency of HCPT on Dox compared with co-administration. The in vivo antitumor results demonstrated that the tumor size after SiO2@AuNP treatment is 1/400 compared with the saline control group and approximately 1/40 of the HCPT/Dox co-treatment group without any noticeable systemic toxicity. PMID- 26561937 TI - Method of carrier-free delivery of therapeutic RNA importable into human mitochondria: Lipophilic conjugates with cleavable bonds. AB - Defects in mitochondrial DNA often cause neuromuscular pathologies, for which no efficient therapy has yet been developed. MtDNA targeting nucleic acids might therefore be promising therapeutic candidates. Nevertheless, mitochondrial gene therapy has never been achieved because DNA molecules can not penetrate inside mitochondria in vivo. In contrast, some small non-coding RNAs are imported into mitochondrial matrix, and we recently designed mitochondrial RNA vectors that can be used to address therapeutic oligoribonucleotides into human mitochondria. Here we describe an approach of carrier-free targeting of the mitochondrially importable RNA into living human cells. For this purpose, we developed the protocol of chemical synthesis of oligoribonucleotides conjugated with cholesterol residue through cleavable covalent bonds. Conjugates containing pH triggered hydrazone bond were stable during the cell transfection procedure and rapidly cleaved in acidic endosomal cellular compartments. RNAs conjugated to cholesterol through a hydrazone bond were characterized by efficient carrier-free cellular uptake and partial co-localization with mitochondrial network. Moreover, the imported oligoribonucleotide designed to target a pathogenic point mutation in mitochondrial DNA was able to induce a decrease in the proportion of mutant mitochondrial genomes. This newly developed approach can be useful for a carrier free delivery of therapeutic RNA into mitochondria of living human cells. PMID- 26561938 TI - Discovery of survival factor for primitive chronic myeloid leukemia cells using induced pluripotent stem cells. AB - A definitive cure for chronic myeloid leukemia (CML) requires identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the primitive hematopoietic cell compartment remains a major limiting factor for their study in humans. Here we show that primitive hematopoietic cells with typical LSC features, including adhesion defect, increased long-term survival and proliferation, and innate resistance to tyrosine kinase inhibitor (TKI) imatinib, can be generated de novo from reprogrammed primary CML cells. Using CML iPSC-derived primitive leukemia cells, we discovered olfactomedin 4 (OLFM4) as a novel factor that contributes to survival and growth of somatic lin(-)CD34(+) cells from bone marrow of patients with CML in chronic phase, but not primitive hematopoietic cells from normal bone marrow. Overall, this study shows the feasibility and advantages of using reprogramming technology to develop strategies for targeting primitive leukemia cells. PMID- 26561939 TI - Relationship of the serotonin transporter gene promoter polymorphism (5-HTTLPR) genotype and serotonin transporter binding to neural processing of negative emotional stimuli. AB - BACKGROUND: The lower-expressing (S') alleles of the serotonin transporter (5 HTT) gene promoter polymorphism (5-HTTLPR) are linked to mood and anxiety related psychopathology. However, the specific neural mechanism through which these alleles may influence emotional and cognitive processing remains unknown. We examined the relationship between both 5-HTTLPR genotype and in vivo 5-HTT binding quantified via PET with amygdala reactivity to emotionally negative stimuli. We hypothesized that 5-HTT binding in both raphe nuclei (RN) and amygdala would be inversely correlated with amygdala reactivity, and that number of S' alleles would correlate positively with amygdala reactivity. METHODS: In medication-free patients with current major depressive disorder (MDD; N=21), we determined 5-HTTLPR genotype, employed functional magnetic resonance imaging (fMRI) to examine amygdala responses to negative emotional stimuli, and used positron emission tomography with [(11)C]DASB to examine 5-HTT binding. RESULTS: [(11)C]DASB binding in RN and amygdala was inversely correlated with amygdala response to negative stimuli. 5-HTTLPR S' alleles were not associated with amygdala response to negative emotional stimuli. LIMITATIONS: Primary limitations are small sample size and lack of control group. CONCLUSIONS: Consistent with findings in healthy volunteers, 5-HTT binding is associated with amygdala reactivity to emotional stimuli in MDD. 5-HTT binding may be a stronger predictor of emotional processing in MDD as compared with 5-HTTLPR genotype. PMID- 26561940 TI - Positive mental health in outpatients with affective disorders: Associations with life satisfaction and general functioning. AB - BACKGROUND: Positive mental health (PMH) is an integral and essential component of health that encompasses emotional, psychological and social well-being. The Keyes' two continua model of mental health and illness posits that mental health status is not merely the absence of mental health problems, and it can be enhanced regardless of a diagnosis of mental illness. The present study hypothesized that mentally ill patients with higher levels of PMH would be associated with better life satisfaction and general functioning. METHODS: 218 outpatients with affective disorders at a tertiary psychiatric hospital were recruited and administered the multidimensional Positive Mental Health instrument, which was validated and developed in Singapore to measure PMH. Depression and anxiety severity were also assessed. Associations of positive mental health with life satisfaction and general functioning were investigated in linear regression models. RESULTS: PMH scores varied largely within patients with depressive and anxiety disorders but did not differ statistically across the two diagnoses, except for emotional support. PMH was associated with both life satisfaction and general functioning with little evidence of confounding by sociodemographic and clinical status. LIMITATIONS: The cross-sectional design of the study could not examine causal relationships. Findings may be restrictive to treatment-seeking population with specific affective disorders. CONCLUSION: Our study provides evidence to support the notion that a good mental health state is not simply the absence of a mental disorder. Mentally ill patients can also have high levels of PMH that possibly have a moderating or mediating effect on the relationship between patients' clinical symptoms and life satisfaction or general functioning. PMID- 26561941 TI - Comorbidity variation in patients with obsessive-compulsive disorder according to symptom dimensions: Results from a large multicentre clinical sample. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) has a heterogeneous and complex phenomenological picture, characterized by different symptom dimensions and comorbid psychiatric disorders, which frequently co-occur or are replaced by others over the illness course. To date, very few studies have investigated the associations between specific OCD symptom dimensions and comorbid disorders. METHODS: Cross-sectional, multicenter clinical study with 1001 well-characterized OCD patients recruited within the Brazilian Research Consortium on Obsessive Compulsive and Related Disorders. The primary instruments were the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) and the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses between symptom dimensions and comorbidities were followed by logistic regression. RESULTS: The most common comorbidities among participants (56.8% females) were major depression (56.4%), social phobia (34.6%), generalized anxiety disorder (34.3%), and specific phobia (31.4%). The aggressive dimension was independently associated with posttraumatic stress disorder (PTSD), separation anxiety disorder, any impulse-control disorder and skin picking; the sexual-religious dimension was associated with mood disorders, panic disorder/agoraphobia, social phobia, separation anxiety disorder, non-paraphilic sexual disorder, any somatoform disorder, body dysmorphic disorder and tic disorders; the contamination-cleaning dimension was related to hypochondriasis; and the hoarding dimension was associated with depressive disorders, specific phobia, PTSD, impulse control disorders (compulsive buying, skin picking, internet use), ADHD and tic disorders. The symmetry-ordering dimension was not independently associated with any comorbidity. LIMITATIONS: Cross-sectional design; participants from only tertiary mental health services; personality disorders not investigated. CONCLUSIONS: Different OCD dimensions presented some specific associations with comorbid disorders, which may influence treatment seeking behaviors and response, and be suggestive of different underlying pathogenic mechanisms. PMID- 26561942 TI - Risk factors for suicide attempts and hospitalizations in a sample of 39,542 French adolescents. AB - BACKGROUND: The high frequency of suicide attempts during adolescence is a serious public health concern. In particular attempts leading to hospitalization, often due to their severity, require careful consideration. METHODS: Participants were drawn from a large adolescent general population survey conducted by the French Monitoring Center for Drugs and Drug Addiction and the National Service department. The final sample included 39,542 adolescents aged 17. Participants were surveyed during the "one-day session of civic and military information" using a pen and paper self-administered questionnaire. RESULTS: Depressive symptoms, family socio-economic status, familial situation, relationship with parents, school situation, substance use and body image were significant independent predictors of lifetime suicide attempts. Among suicide attempts, hospitalization was independently predicted by daily smoking in both genders, school dropout, grade repetition, absence of relationship with the mother, regular cannabis smoking and lifetime other illicit drug use in girls. LIMITATIONS: The main limitation of the present study is the absence of a thorough assessment of psychiatric disorders, depressive symptomatology being the only indicator of mental health status at the time of the survey. Second, the survey was cross-sectional thus limiting the interpretation of the findings. CONCLUSIONS: The variables associated with suicide attempts and among them, those associated with hospitalization should be used to identify and provide additional services to adolescents at risk for serious suicidal behavior. Primary prevention in the field of parenting and family support, as well as intervention tackling normative beliefs related to body image should be considered. PMID- 26561943 TI - The exacerbating influence of hopelessness on other known risk factors for repeat self-harm and suicide. AB - BACKGROUND: Hopelessness is frequently observed in people who harm themselves and is an established risk factor for nonfatal self-harm repetition and suicide. Little is known about how the presence of hopelessness in addition to other risk factors affects subsequent risk. METHOD: Prospective cohort of 19,479 individuals presenting with self-harm to one of three English Emergency Departments between 1st January 2000 and 31st December 2010. Repeat self-harm and suicide deaths within twelve months of the first assessed episode were identified. Cox Proportional Hazards models were used to estimate Hazard Ratios (HRs) for risk factors with and without hopelessness. RESULTS: A clinical impression of hopelessness was associated with increased risk of further self-harm (HR 1.35, 95% CI 1.16-1.58) and suicide (HR 2.56, CI 1.10-5.96) in the year following an index episode. For individuals who were living alone or homeless, unemployed, reported problems with housing, had received psychiatric treatment in the past, were currently receiving treatment or used alcohol during the self-harm episode, an exacerbation of an already elevated risk of repetition was observed amongst those who were assessed as hopeless. Where individuals presented with forensic problems, physical health problems or bereavement, an increase in risk was only observed for those who were also assessed as hopeless. LIMITATIONS: A clinical impression of hopelessness was assigned using a binary "yes"/"no" classification rather than a validated scale. CONCLUSIONS: Hopelessness intensifies the impact of several known risk factors for adverse outcomes following self-harm. These findings highlight the importance of identifying and therapeutically addressing this dynamic but potentially modifiable clinical risk factor during the psychosocial assessment and in subsequent care. PMID- 26561944 TI - Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on larval zebrafish behavior. AB - Developmental disorders such as anxiety, autism, and attention deficit hyperactivity disorders have been linked to exposure to polychlorinated biphenyls (PCBs), a ubiquitous anthropogenic pollutant. The zebrafish is widely recognized as an excellent model system for assessing the effects of toxicant exposure on behavior and neurodevelopment. In the present study, we examined the effect of sub-chronic embryonic exposure to the PCB mixture, Aroclor (A) 1254 on anxiety related behaviors in zebrafish larvae at 7 days post-fertilization (dpf). We found that exposure to low concentrations of A1254, from 2 to 26 h post fertilization (hpf) induced specific behavioral defects in two assays. In one assay with intermittent presentations of a moving visual stimulus, 5 ppm and 10 ppm PCB-exposed larvae displayed decreased avoidance behavior but no significant differences in thigmotaxis or freezing relative to controls. In the other assay with intermittent presentations of a moving visual stimulus and a stationary visual stimulus, 5 ppm and 10 ppm PCB-exposed larvae had elevated baseline levels of thigmotaxis but no significant differences in avoidance behavior relative to controls. The 5 ppm larvae also displayed higher terminal levels of freezing relative to controls. Collectively, our results show that exposure to ecologically valid PCB concentrations during embryonic development can induce functional deficits and alter behavioral responses to a visual threat. PMID- 26561945 TI - Trans-generational transmission of neurobehavioral impairments produced by developmental methylmercury exposure in zebrafish (Danio rerio). AB - Our previous study showed that embryonic exposures to methylmercury (MeHg) produced learning impairments in adult zebrafish. The present study investigated the persistency of learning impairments in the second (F2) and third (F3) generations of zebrafish developmentally exposed to MeHg as embryos using active avoidance conditioning as the behavioral paradigm. The results showed that the control zebrafish learned avoidance responses during training and significantly increased avoidance responses during testing. The F2 generation of zebrafish developmentally exposed to MeHg as embryos displayed no significant changes in avoidance responses from training to testing, showing persistent learning impairments, while the F3 generation of zebrafish developmentally exposed as embryos to only the higher concentration of MeHg showed persistent learning impairments. Results of the present study showed that learning impairments produced by embryonic MeHg exposure persisted for at least three generations, demonstrating trans-generational effects of embryonic exposure to MeHg. PMID- 26561947 TI - Reaching out to Ebola victims: Coercion, persuasion or an appeal for self sacrifice? AB - The 2014-2015 Ebola crisis in West Africa has highlighted the practical limits of upholding human rights and common ethical principles when applying emergency public-health measures. The role of medical teams in the implementation of quarantine and isolation has been equivocal, particularly when such measures are opposed by communities who are coerced by the temporary suspension of civil liberties. In their encounters with Ebola victims, outreach teams face moral dilemmas, where the boundaries are unclear between coercion, persuasion and appeals for self-sacrifice. For those teams, we propose a set of practical recommendations aimed at respecting the autonomy of epidemic victims and easing tensions within communities. We recognize that some of these recommendations are progressively achievable, depending on the specific stage or setting of an outbreak. Yet with the increasing availability of experimental treatments and research interventions, weighing patients' autonomy against the common good will become an even more pressing ethical obligation. PMID- 26561946 TI - Distinctive effects of nicotinic receptor intracellular-loop mutations associated with nocturnal frontal lobe epilepsy. AB - Previously characterized nicotinic acetylcholine receptor (nAChR) autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)-associated mutations are found in alpha2, alpha4 and beta2 subunit transmembrane (TM) domains. They predominantly increase ACh potency and, for beta2-subunit mutants, increase macroscopic currents. Two recently-identified mutations, alpha4(R336H) and beta2(V337G), located in the intracellular cytoplasmic loop (C2) have been associated with non-familial NFLE. Effects of these mutations on alpha4beta2 nAChR function and expression were studied for the first time, using two electrode voltage clamp recordings in Xenopus laevis oocytes. Biased-ratio preparations elucidated the mutations' effects at alternate isoforms: high sensitivity [HS; (alpha4)2(beta2)3] or low-sensitivity [LS; (alpha4)3(beta2)2] via 1:10 or 30:1 [alpha4:beta2] cRNA injection ratios, respectively. An unbiased (1:1 [alpha4:beta2] cRNA) injection ratio was also used to study potential shifts in isoform expression. alpha4(R336H)-containing receptors showed significant increases in maximal ACh-induced currents (Imax) in all preparations (140% increase compared to wild type control). beta2(V337G)-containing receptors significantly increased Imax in the LS-favoring preparation (20% increase compared to control). Expression of either mutation consistently produced enrichment of HS-isoform expression in all preparations. alpha4beta2-nAChR harboring either NFLE mutant subunit showed unchanged ACh, sazetidine-A, nicotine, cytisine and mecamylamine potency. However, both mutant subunits enhanced partial agonist efficacies in the LS-biased preparation. Using beta2 subunit-specific [(125)I]mAb 295 immunolabeling, nAChR cell-surface expression was determined. Antibody binding studies revealed that the beta2(V337G) mutation tended to reduce cell-surface expression, and function per receptor was significantly increased by either NFLE mutant subunit in HS-favoring preparations. These findings identify both common and differing features between TM- and C2-domain AD/NFLE-associated mutations. As we discuss, the shared features may be particularly salient to AD/NFLE etiology. PMID- 26561948 TI - Combined therapy of oncolytic adenovirus and temozolomide enhances lung cancer virotherapy in vitro and in vivo. AB - Oncolytic adenoviruses (OAds) are very promising for the treatment of lung cancer. However, OAd-based monotherapeutics have not been effective during clinical trials. Therefore, the effectiveness of virotherapy must be enhanced by combining OAds with other therapies. In this study, the therapeutic potential of OAd in combination with temozolomide (TMZ) was evaluated in lung cancer cells in vitro and in vivo. The combination of OAd and TMZ therapy synergistically enhanced cancer cell death; this enhanced cancer cell death may be explained via three related mechanisms: apoptosis, virus replication, and autophagy. Autophagy inhibition partially protected cancer cells from this combined therapy. This combination significantly suppressed the growth of subcutaneous H441 lung cancer xenograft tumors in athymic nude mice. In this study, we have provided an experimental rationale to test OAds in combination with TMZ in a lung cancer clinical trial. PMID- 26561949 TI - The amelioration of composite tissue allograft rejection by TIM-3-modified dendritic cell: Regulation of the balance of regulatory and effector T cells. AB - T cell-dependent immune responses play a central role in allograft rejection. Exploring ways to disarm alloreactive T cells represents a potential strategy to promote long-term allograft acceptance and survival. T cell Ig domain and mucin domain 3 (TIM-3) has previously been demonstrated as a central regulator of T helper 1 (Th1) responses and immune tolerance. Hence, TIM-3 may be an important molecule for decreasing immunological rejection during composite tissue allotransplantation (CTA). In this study, BALB/c and C57BL/6 mice were chosen as the experimental animals. The effects of TIM-3 on allograft rejection were explored using TIM-3-modified mature dendritic cells (TIM-3 mDCs). A laser speckle blood flow (LSBF) imager was used to evaluate blood distribution of the BALB/c mice. ELISA, MTT, ELISPOT assays and flow cytometry analysis were carried out for further researches. We found that TIM-3 could obviously prolong the survival time of the transplanted limbs. And TIM-3 could mitigate the immune response and thus enhance immune tolerance after CTA. Also, TIM-3 can induce lymphocyte hyporesponsiveness, including facilitating lymphocyte apoptosis, decreasing lymphocyte proliferation, and influencing the secretion of inflammatory cytokines by CD4(+) T cells. Furthermore, TIM-3 overexpression could induce CD4(+) T cells to differentiate into regulatory T cells (Tregs), which recalibrate the effector and regulatory arms of the alloimmune response. In summary, we concluded that TIM-3 can mitigate allograft rejection and thus enhance immune tolerance by inducing lymphocyte hyporesponsiveness and increasing the number of Tregs of the alloimmune response. TIM-3 may be a potential therapeutic molecule for allograft rejection in CTA. PMID- 26561950 TI - Predicting drug resistance in adult patients with generalized epilepsy: A case control study. AB - OBJECTIVES: Using an adult cohort of patients with generalized epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy (DRE), which if identifiable would allow patients to receive earlier treatment and more specifically individualized treatment plans. METHODS: For the case-control study, 118 patients with generalized epilepsy (GE) between the ages of 18 and 75 were included after selection from a database of 800 patients referred from throughout the Saskatchewan Epilepsy Program. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis. RESULTS: Forty-four (37%) patients fulfilled the definition of DRE (cases), and seizures in 74 (63%) patients were not intractable (controls). Patients with DRE were significantly younger than the controls at the onset of epilepsy (6.6 vs. 18.8 years, p=<0.001). Significant variables on univariate analysis were the following: epilepsy diagnosed prior to 12 years (OR: 12.1, CI: 4.8-29.9, p<0.001), previous history of status epilepticus (OR: 15.1, CI: 3.2-70.9, p<0.001), developmental delay (OR: 12.6, CI: 4.9-32, p<0.001), and cryptogenic epilepsy (OR: 10.5, CI: 3.9-27.8, p<0.001). Our study showed some protective factors for DRE such as a good response to first AED, idiopathic etiology, and history of febrile seizures. In the logistic regression analysis, two variables remained statistically significant: developmental delay and more than one seizure type. CONCLUSION: Our study has identified a set of variables that predict DRE in patients with generalized epilepsy. Risk factors identified in our study are similar to those previously identified in pediatric studies, however, our study is specifically tailored to adult patients with generalized epilepsy. PMID- 26561951 TI - Vascular Factors and Cognitive Dysfunction in Alzheimer Disease. AB - BACKGROUND: The purpose of the present study was to assess the influence of vascular factors on the degree of intensity and rate of progression of cognitive disorders in the course of Alzheimer Disease (AD). MATERIAL AND METHODS: The research group consisted of 39 persons, all of whom were diagnosed with AD according to the NINCDS/ADRDA criteria. We divided these patients into 2 subgroups, based on the vascular factors measured by the modified Hachinski Ischemic Scale (Ha-mod): group A, without the vascular component (HA-mod score of 0-1 point), and group B, with the vascular component (a score over 1 point). Cognitive functions were evaluated at baseline and again 2 years later, using the Cognitive Part of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS: We found that the patients from subgroup B, with the stronger vascular component, demonstrated the highest intensity of cognitive disorders at baseline, both in terms of the overall ADAS-cog score, and in the subscores for ideational praxis, orientation, spoken language ability, comprehension of spoken language, and word finding difficulty in spontaneous speech. Another variable which was connected with the intensity of dementia was age. After 2 years, however, the rate of progression of cognitive disorders was not significantly different between the 2 groups. CONCLUSIONS: The severity of vascular factors correlates directly with the intensity of cognitive disturbances. At the 2-year follow-up examination, however, no correlation was observed in the research group between greater vascular involvement and more rapid progression of cognitive disorders, as measured by the ADAS-cog scale. PMID- 26561952 TI - Severe Respiratory Failure Due to Interferon Beta-Related Pulmonary Hypertension. AB - Pulmonary arterial hypertension (PAH) is an uncommon but devastating disease. There is increasing evidence of a correlation between interferon (IFN) use and PAH. Very few cases of PAH in patients treated with IFN are reported in literature. We report a case of a 47-year-old woman with previous diagnosis of multiple sclerosis treated with IFN beta-1a for 6 years, presenting severe respiratory failure (paO2/FiO2 228) because of pulmonary hypertension. The suspension of the drug along with the treatment of PAH improved the clinical picture allowing cessation of oxygen administration. Pathophysiological effects of IFN on endothelial vascular cells are discussed. PMID- 26561953 TI - Ocular Trauma: Automatic Nail Gun. PMID- 26561954 TI - Uniformly Sclerotic Diffuse Large B-Cell Lymphoma of the Orbit. AB - Over a year, a 51-year-old man developed a mass in the anteromedial orbit in the region of the lacrimal sac that caused epiphora. Imaging studies disclosed no bone destruction. On biopsy, a sclerotic lesion was discovered populated by hyperchromatic cells that had been apparently distorted by crush artifact, indicative of fragile cells. The lesion simulated a sclerosing inflammatory process or a desmoplastic metastatic carcinoma. CD20 revealed that the background cells were large neoplastic B-lymphocytes. A systemic workup uncovered widespread skeletal disease. The patient is undergoing R-CHOP chemotherapy with a relatively favorable prognosis due to negative testing for MYC. PMID- 26561955 TI - Extranodal Rosai-Dorfman Disease of the Orbit: Clinical Features of 8 Cases. AB - PURPOSE: To report on the presentation, radiography, histology, and treatment of 8 cases of extranodal Rosai-Dorfman disease involving the orbit. METHODS: Multicenter retrospective case series. RESULTS: Five males and 3 females had a median age of 10 years (range 2-78 years). Presenting signs and symptoms included proptosis, periorbital pain, palpable mass, blepharoptosis, decreased vision, diplopia, impaired extraocular motility, and afferent pupillary defect. Four patients had bilateral orbital disease, while 4 had unilateral disease. Six cases were extraconal, 1 was intraconal, and 1 was both intra- and extra-conal. Four cases had only extranodal disease without lymphadenopathy (3 of which had localized orbital disease). Diagnosis was confirmed by exam, orbital, and/or systemic radiography, and biopsy in all cases. Treatment strategies included excision or debulking, systemic corticosteroids, chemotherapy, radiotherapy, observation or a combination thereof. At last follow up, 4 patients were disease free, while 4 had residual improved disease. CONCLUSIONS: Rosai-Dorfman disease of the orbit is a rare clinical entity. Purely extranodal disease is rare, with isolated orbital disease being exceedingly rare. This study is unique in that 4 of 8 patients had strictly isolated extranodal disease of the orbit. A large majority of the cases had disease in the extraconal space, contrasting with previous reports. In addition, lacrimal gland disease, particularly bilateral involvement, was prominent in the current study. Although there is no consensus on treatment, surgical excision should be attempted if plausible in symptomatic patients especially if the orbit represents a localized site of disease. PMID- 26561956 TI - In Vivo and Ex Vivo Confocal Microscopy for the Management of a Melanoma of the Eyelid Margin. PMID- 26561957 TI - The Oval Female Facial Shape--A Study in Beauty. AB - PURPOSE: Our understanding of who is beautiful seems to be innate but has been argued to conform to mathematical principles and proportions. One aspect of beauty is facial shape that is gender specific. In women, an oval facial shape is considered attractive. OBJECTIVE: To study the facial shape of beautiful actors, pageant title winners, and performers across ethnicities and in different time periods and to construct an ideal oval shape based on the average of their facial shape dimensions. METHODS: Twenty-one full-face photographs of purportedly beautiful female actors, performers, and pageant winners were analyzed and an oval constructed from their facial parameters. RESULTS: Only 3 of the 21 faces were totally symmetrical, with the most larger in the left upper and lower face. The average oval was subsequently constructed from an average bizygomatic distance (horizontal parameter) of 4.3 times their intercanthal distance (ICD) and a vertical dimension that averaged 6.3 times their ICD. CONCLUSION: This average oval could be fitted to many of the individual subjects showing a smooth flow from the forehead through temples, cheeks, jaw angle, jawline, and chin with all these facial aspects abutting the oval. Where they did not abut, treatment may have improved these subjects. PMID- 26561958 TI - Hemosiderin Hyperpigmentation: Successful Treatment With Q-Switched 755-nm Laser Therapy. PMID- 26561959 TI - Use of Bone Anchor Systems for the Reconstruction of Medial Canthal Tendon. PMID- 26561960 TI - Intraoperative Ultrasound to Accurately Gauge Scar Thickness and Identify Altered Intrascar Anatomy During Multimodal Revision of a Hypertrophic Chest Wall Burn Scar. PMID- 26561961 TI - Concurrent Development of Endurance Capacity and Explosiveness: Training Characteristics of World-Class Nordic-Combined Athletes. AB - Performing at an elite level in Nordic combined (NC) requires both the explosiveness required for ski jumping performance and the endurance capacity required for cross-country skiing. PURPOSE: To describe the characteristics of world-class NC athletes' training and determine how endurance and non-endurance (ie, strength, power, and ski jumping) training is periodized. METHODS: Annual training characteristics and the periodization of endurance and non-endurance training were determined by analyzing the training diaries of 6 world-class NC athletes. RESULTS: Of 846 +/- 72 annual training hours, 540 +/- 37 h were endurance training, with 88.6% being low-, 5.9% moderate-, and 5.5% high intensity training. While training frequency remained relatively constant, the total training volume was reduced from the general preparatory to the competition phase, primarily due to less low- and moderate-intensity training (P < .05). A total of 236 +/- 55 h/y were spent as non-endurance training, including 211 +/- 44 h of power and ski-jump-specific training (908 +/- 165 ski jumps and ski-jump imitations). The proportion of non-endurance training increased significantly toward the competition phase (P < .05). CONCLUSION: World-class NC athletes reduce the volume of low- and moderate-intensity endurance training toward the competition phase, followed by an increase in the relative contribution of power and ski-jump training. These data provide novel insight on how successful athletes execute their training and may facilitate more-precise coaching of future athletes in this sport. In addition, this information is of high relevance for the training organization of other sports that require optimization of 2 fundamentally different physical capacities. PMID- 26561962 TI - 12,17-Cyclojatrophane and Jatrophane Constituents of Euphorbia welwitschii. AB - Euphowelwitschines A (1) and B (2), isolated from a methanolic extract of Euphorbia welwitschii, exhibit a rare combination of structural features in having a 5/8/8 fused-ring system and a 12,15-ether bridge. Moreover, the isolation of the additional new compounds welwitschene (3) and epoxywelwitschene (4) has provided insights into the biogenetic pathway of 12,17-cyclojatrophanes. The structures of 1-4 were determined by spectroscopic methods inclusive of 1D and 2D NMR experiments and X-ray crystallography for compounds 1 and 2. Preliminary information on the selective antiproliferative activity of compounds 1-4 is also described. PMID- 26561963 TI - Heterogeneously-Grown Tunable Tensile Strained Germanium on Silicon for Photonic Devices. AB - The growth, structural and optical properties, and energy band alignments of tensile-strained germanium (epsilon-Ge) epilayers heterogeneously integrated on silicon (Si) were demonstrated for the first time. The tunable epsilon-Ge thin films were achieved using a composite linearly graded InxGa1-xAs/GaAs buffer architecture grown via solid source molecular beam epitaxy. High-resolution X-ray diffraction and micro-Raman spectroscopic analysis confirmed a pseudomorphic epsilon-Ge epitaxy whereby the degree of strain varied as a function of the In(x)Ga(1-x)As buffer indium alloy composition. Sharp heterointerfaces between each epsilon-Ge epilayer and the respective In(x)Ga(1-x)As strain template were confirmed by detailed strain analysis using cross-sectional transmission electron microscopy. Low-temperature microphotoluminescence measurements confirmed both direct and indirect bandgap radiative recombination between the Gamma and L valleys of Ge to the light-hole valence band, with L-lh bandgaps of 0.68 and 0.65 eV demonstrated for the 0.82 +/- 0.06% and 1.11 +/- 0.03% strained Ge on Si, respectively. Type-I band alignments and valence band offsets of 0.27 and 0.29 eV for the epsilon-Ge/In(0.11)Ga(0.89)As (0.82%) and epsilon-Ge/In(0.17)Ga(0.83)As (1.11%) heterointerfaces, respectively, show promise for epsilon-Ge carrier confinement in future nanoscale optoelectronic devices. Therefore, the successful heterogeneous integration of tunable tensile-strained Ge on Si paves the way for the design and implementation of novel Ge-based photonic devices on the Si technology platform. PMID- 26561964 TI - Impacts of Combustion Conditions and Photochemical Processing on the Light Absorption of Biomass Combustion Aerosol. AB - The aim was to identify relationships between combustion conditions, particle characteristics, and optical properties of fresh and photochemically processed emissions from biomass combustion. The combustion conditions included nominal and high burn rate operation and individual combustion phases from a conventional wood stove. Low temperature pyrolysis upon fuel addition resulted in "tar-ball" type particles dominated by organic aerosol with an absorption Angstrom exponent (AAE) of 2.5-2.7 and estimated Brown Carbon contributions of 50-70% to absorption at the climate relevant aethalometer-wavelength (520 nm). High temperature combustion during the intermediate (flaming) phase was dominated by soot agglomerates with AAE 1.0-1.2 and 85-100% of absorption at 520 nm attributed to Black Carbon. Intense photochemical processing of high burn rate flaming combustion emissions in an oxidation flow reactor led to strong formation of Secondary Organic Aerosol, with no or weak absorption. PM1 mass emission factors (mg/kg) of fresh emissions were about an order of magnitude higher for low temperature pyrolysis compared to high temperature combustion. However, emission factors describing the absorption cross section emitted per kg of fuel consumed (m(2)/kg) were of similar magnitude at 520 nm for the diverse combustion conditions investigated in this study. These results provide a link between biomass combustion conditions, emitted particle types, and their optical properties in fresh and processed plumes which can be of value for source apportionment and balanced mitigation of biomass combustion emissions from a climate and health perspective. PMID- 26561966 TI - Depicting Visual Motion in Still Images: Forward Leaning and a Left to Right Bias for Lateral Movement. AB - What artistic conventions are used to convey the motion of animate and inanimate items in still images, such as drawings and photographs? One graphic convention involves depicting items leaning forward into their movement, with greater leaning conveying greater speed. Though this convention could derive from the natural leaning forward of people and animals as they run, it is also applied to depictions of inanimate objects (eg cars and trains). It is proposed that it is this convention that allows the italicization of text to convey notions of motion and speed. Evidence for this is obtained from three sources: the use of italicization on book covers (in book titles); judgments of typeface connotations; and performance measures during the semantic classification of words appearing in italicized and non-italicized fonts. Inspection of the availability of italic fonts in Hebrew indicates an additional artistic convention for conveying motion, based on a fundamental bias, yet to be confirmed, for people to expect to see, or prefer to see, lateral movement (real or implied) in a left to right direction, rather than a right to left direction. Evidence for such a bias is found in photographs of a range of animate and inanimate items archived on Google Images. Whereas a rightward bias is found for photographs of animate and inanimate items in motion (the more so, the faster the motion being conveyed), either no bias or a leftward bias is found for the same items in static pose. Possible origins of a fundamental left to right bias for visual motion, and future lines of research able to evaluate them, are identified. PMID- 26561965 TI - Carbohydrate-Aromatic Interactions in Proteins. AB - Protein-carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures of proteins with noncovalently bound carbohydrates. Within the carbohydrate-binding pockets, aliphatic hydrophobic residues are disfavored, whereas aromatic side chains are enriched. The greatest preference is for tryptophan with an increased prevalence of 9-fold. Variations in the spatial orientation of amino acids around different monosaccharides indicate specific carbohydrate C-H bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C-H bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C-H bonds engage more often in CH pi interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate-aromatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C-H bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein-carbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein-carbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites. PMID- 26561967 TI - Nonuniform Changes in the Distribution of Visual Attention from Visual Complexity and Action: A Driving Simulation Study. AB - Researchers acknowledge the interplay between action and attention, but typically consider action as a response to successful attentional selection or the correlation of performance on separate action and attention tasks. We investigated how concurrent action with spatial monitoring affects the distribution of attention across the visual field. We embedded a functional field of view (FFOV) paradigm with concurrent central object recognition and peripheral target localization tasks in a simulated driving environment. Peripheral targets varied across 20-60 deg eccentricity at 11 radial spokes. Three conditions assessed the effects of visual complexity and concurrent action on the size and shape of the FFOV: (1) with no background, (2) with driving background, and (3) with driving background and vehicle steering. The addition of visual complexity slowed task performance and reduced the FFOV size but did not change the baseline shape. In contrast, the addition of steering produced not only shrinkage of the FFOV, but also changes in the FFOV shape. Nonuniform performance decrements occurred in proximal regions used for the central task and for steering, independent of interference from context elements. Multifocal attention models should consider the role of action and account for nonhomogeneities in the distribution of attention. PMID- 26561968 TI - Simulation of Driving in Low-Visibility Conditions: Does Stereopsis Improve Speed Perception? AB - Laboratory-based studies of perceived speed show that, under most circumstances, perceived speed is reduced as a function of contrast. However, a recent investigation of perceived vehicular speed while driving around a closed road circuit showed no such effect (Owens, Wood, & Carberry, 2010, Perception, 39: , 1199-1215). We sought to probe the source of this discrepancy, asking whether the presence or absence of stereoscopic motion information might account for the difference in results. In a two-alternative forced-choice psychophysical speed discrimination task, observers compared the speed of high- and low-contrast driving clips filmed with a 3-D camera and presented either stereoscopically (3 D) or monoscopically (2-D). Although perceived speed was reduced at low contrast, the size of this misperception was equivalent for 2-D and 3-D presentations. However, the inclusion of stereoscopic cues to vehicular speed caused significant improvements in the precision of speed judgments. It is concluded that although stereopsis can provide access to valuable information on perceived speed, contrast-independent speed estimation as demonstrated by Owens et al. (2010) is more likely to reflect the use of the full visual field in a real driving situation (compared with limited field of view simulations), or the additional contributions of nonvisual cues rather than stereopsis. PMID- 26561969 TI - Temporal Processing in Bistable Perception of the Necker Cube. AB - Perception of ambiguous figures is unstable and alternates repeatedly between possible interpretations. Some approaches to explaining this phenomenon have, so far, assumed low-level bottom-up mechanisms like adaptation and mutual inhibition of underlying neural assemblies. In contrast, less precise top-down approaches assume high-level attentional control mechanisms generalised across sensory modalities. In the current work we focused on specific aspects of the top-down approach. In a first study we used dwell times (periods of transiently stable percepts) and the parameters of dwell time distribution functions to compare the dynamics of perceptual alternations between visual (Necker cube) and auditory ambiguity (verbal transformation effect). In a second study we compared the endogenous alternation dynamics of the Necker cube with parameters from two attention tasks with different regimes of temporal dynamics. The first attention task (d2) is characterised by endogenous self-paced dynamics, similar to the dynamics underlying perceptual alternations of ambiguous figures, and we found clear correlations between dwell time parameters (Necker cube) and processing speed (d2 task). The temporal dynamics of the second (go/no-go) attention task, in contrast, are exogenously governed by the stimulus protocol, and we found no statistically significant correlation with the Necker cube data. Our results indicate that both perceptual instability and higher-level attentional tasks are linked to endogenous brain dynamics on a global coordinating level beyond sensory modalities. PMID- 26561970 TI - Volitional Mechanisms Mediate the Cuing Effect of Pitch on Attention Orienting: The Influences of Perceptual Difficulty and Response Pressure. AB - Our cognitive system tends to link auditory pitch with spatial location in a specific manner (ie high-pitched sounds are usually associated with an upper location, and low sounds are associated with a lower location). Recent studies have demonstrated that this cross-modality association biases the allocation of visual attention and affects performance despite the auditory stimuli being irrelevant to the behavioural task. There is, however, a discrepancy between studies in their interpretation of the underlying mechanisms. Whereas we have previously claimed that the pitch-location mapping is mediated by volitional shifts of attention (Chiou & Rich, 2012, Perception, 41: , 339-353), other researchers suggest that this cross-modal effect reflects automatic shifts of attention (Mossbridge, Grabowecky, & Suzuki, 2011, Cognition, 121: , 133-139). Here we report a series of three experiments examining the effects of perceptual and response-related pressure on the ability of nonpredictive pitch to bias visual attention. We compare it with two control cues: a predictive pitch that triggers voluntary attention shifts and a salient peripheral flash that evokes involuntary shifts. The results show that the effect of nonpredictive pitch is abolished by pressure at either perceptual or response levels. By contrast, the effects of the two control cues remain significant, demonstrating the robustness of informative and perceptually salient stimuli in directing attention. This distinction suggests that, in contexts of high perceptual demand and response pressure, cognitive resources are primarily engaged by the task-relevant stimuli, which effectively prevents uninformative pitch from orienting attention to its cross-modally associated location. These findings are consistent with the hypothesis that the link between pitch and location affects attentional deployment via volitional rather than automatic mechanisms. PMID- 26561971 TI - Perception of Animacy from the Motion of a Single Sound Object. AB - Research in the visual modality has shown that the presence of certain dynamics in the motion of an object has a strong effect on whether or not the entity is perceived as animate. Cues for animacy are, among others, self-propelled motion and direction changes that are seemingly not caused by entities external to, or in direct contact with, the moving object. The present study aimed to extend this research into the auditory domain by determining if similar dynamics could influence the perceived animacy of a sound source. In two experiments, participants were presented with single, synthetically generated 'mosquito' sounds moving along trajectories in space, and asked to rate how certain they were that each sound-emitting entity was alive. At a random point on a linear motion trajectory, the sound source would deviate from its initial path and speed. Results confirm findings from the visual domain that a change in the velocity of motion is positively correlated with perceived animacy, and changes in direction were found to influence animacy judgment as well. This suggests that an ability to facilitate and sustain self-movement is perceived as a living quality not only in the visual domain, but in the auditory domain as well. PMID- 26561972 TI - Effects of Frequency Separation and Diotic/Dichotic Presentations on the Alternation Frequency Limits in Audition Derived from a Temporal Phase Discrimination Task. AB - Temporal phase discrimination is a useful psychophysical task to evaluate how sensory signals, synchronously detected in parallel, are perceptually bound by human observers. In this task two stimulus sequences synchronously alternate between two states (say, A-B-A-B and X-Y-X-Y) in either of two temporal phases (ie A and B are respectively paired with X and Y, or vice versa). The critical alternation frequency beyond which participants cannot discriminate the temporal phase is measured as an index characterizing the temporal property of the underlying binding process. This task has been used to reveal the mechanisms underlying visual and cross-modal bindings. To directly compare these binding mechanisms with those in another modality, this study used the temporal phase discrimination task to reveal the processes underlying auditory bindings. The two sequences were alternations between two pitches. We manipulated the distance between the two sequences by changing intersequence frequency separation, or presentation ears (diotic vs dichotic). Results showed that the alternation frequency limit ranged from 7 to 30 Hz, becoming higher as the intersequence distance decreased, as is the case with vision. However, unlike vision, auditory phase discrimination limits were higher and more variable across participants. PMID- 26561973 TI - A New Demonstration of the Illusory Letters Phenomenon: Graphemic Restoration in Arabic Word Perception. AB - The illusory letters phenomenon (ILP) is a unique demonstration that words can be perceived as complete even when letters are physically absent. However, the ILP has only ever been reported for a Latinate language (English), and it is unknown whether the illusion occurs for alphabetic languages with fundamentally different visual properties. Here we report a demonstration of the ILP for Arabic in which stimuli containing only the exterior letters of three-letter Arabic words and a nonsense pattern in the interior position were presented to fluent Arabic readers. Despite being incomplete, participants perceived these stimuli as complete Arabic words with all letters visible in their appropriate positions, and were unable to distinguish between illusory and normal displays. This finding provides an important extension of the original ILP and suggests that alphabetic languages may be widely susceptible to the phenomenon and reading generally may occur as a process augmented by illusory percepts. PMID- 26561974 TI - A New Illusion at Your Elbow. AB - On experiencing distal-proximal tactile motion on the volar side of the forearm starting at the wrist, subjects significantly anticipate touch of the elbow crook. This illusion, popular as a children's game, was quantified in ninety participants (forty-seven women) on both arms. As a top-down explanation of the illusion, we discuss a model of Bayesian inferences. As a bottom-up contribution, we consider afterdischarges of cortical neurons, which receive input from skin mechanoreceptors specifically driven by slow-motion tactile stimuli. Like previously described illusions, the elbow crook illusion is larger on the nondominant arm. Women showed a smaller illusion than men, giving testimony to their reportedly superior cutaneous sensitivity. PMID- 26561975 TI - Review: Structural Information Theory: The Simplicity of Visual Form, Simplicity in Vision: A Multidisciplinary Account of Perceptual Organization, Psychology of Touch and Blindness, Psychology of Touch and Blindness. PMID- 26561976 TI - Organic Oxidations Using Geomimicry. AB - Oxidations of phenylacetic acid to benzaldehyde, benzyl alcohol to benzaldehyde, and benzaldehyde to benzoic acid have been observed, in water as the solvent and using only copper(II) chloride as the oxidant. The reactions are performed at 250 degrees C and 40 bar, conditions that mimic hydrothermal reactions that are geochemically relevant. Speciation calculations show that the oxidizing agent is not freely solvated copper(II) ions, but complexes of copper(II) with chloride and carboxylate anions. Measurements of the reaction stoichiometries and also of substituent effects on reactivity allow plausible mechanisms to be proposed. These oxidation reactions are relevant to green chemistry in that they proceed in high chemical yield in water as the solvent and avoid the use of toxic heavy metal oxidizing reagents. PMID- 26561977 TI - Biomarker Development for Intraductal Papillary Mucinous Neoplasms Using Multiple Reaction Monitoring Mass Spectrometry. AB - Intraductal papillary mucinous neoplasm (IPMN) is a common precursor of pancreatic cancer (PC). Much clinical attention has been directed toward IPMNs due to the increase in the prevalence of PC. The diagnosis of IPMN depends primarily on a radiological examination, but the diagnostic accuracy of this tool is not satisfactory, necessitating the development of accurate diagnostic biomarkers for IPMN to prevent PC. Recently, high-throughput targeted proteomic quantification methods have accelerated the discovery of biomarkers, rendering them powerful platforms for the evolution of IPMN diagnostic biomarkers. In this study, a robust multiple reaction monitoring (MRM) pipeline was applied to discovery and verify IPMN biomarker candidates in a large cohort of plasma samples. Through highly reproducible MRM assays and a stringent statistical analysis, 11 proteins were selected as IPMN marker candidates with high confidence in 184 plasma samples, comprising a training (n = 84) and test set (n = 100). To improve the discriminatory power, we constructed a six-protein panel by combining marker candidates. The multimarker panel had high discriminatory power in distinguishing between IPMN and controls, including other benign diseases. Consequently, the diagnostic accuracy of IPMN can be improved dramatically with this novel plasma-based panel in combination with a radiological examination. PMID- 26561978 TI - Direct Observation of Confinement-Induced Charge Inversion at a Metal Surface. AB - Surface interactions across water are central to areas from nanomedicine to colloidal stability. They are predominantly a combination of attractive but short ranged dispersive (van der Waals) forces, and long-ranged electrostatic forces between the charged surfaces. Here we show, using a surface force balance, that electrostatic forces between two surfaces across water, one at constant charge while the other (a molecularly smooth metal surface) is at constant potential of the same sign, may revert smoothly from repulsion to attraction on progressive confinement of the aqueous intersurface gap. This remarkable effect, long predicted theoretically in the classic Gouy-Chapman (Poisson-Boltzmann) model but never previously experimentally observed, unambiguously demonstrates surface charge reversal at the metal-water surface. This experimental confirmation emphasizes the implications for interactions of dielectrics with metal surfaces in aqueous media. PMID- 26561979 TI - Discovery and Pharmacology of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors. AB - DGAT2 plays a critical role in hepatic triglyceride production, and data suggests that inhibition of DGAT2 could prove to be beneficial in treating a number of disease states. This article documents the discovery and optimization of a selective small molecule inhibitor of DGAT2 as well as pharmacological proof of biology in a mouse model of triglyceride production. PMID- 26561980 TI - Endothelin-1 contributes to the progression of renal injury in sickle cell disease via reactive oxygen species. AB - BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) is increased in patients with sickle cell disease and may contribute to the development of sickle cell nephropathy. The current study was designed to determine whether ET-1 acting via the ETA receptor contributes to renal injury in a mouse model of sickle cell disease. EXPERIMENTAL APPROACH: Adult, humanized HbSS (homozygous for sickle Hb) mice had increased ET-1 mRNA expression in both the cortex and the glomeruli compared with mice heterozygous for sickle and Hb A (HbAS controls). In the renal cortex, ETA receptor mRNA expression was also elevated in HbSS (sickle) mice although ETB receptor mRNA expression was unchanged. Ligand binding assays confirmed that sickle mice had increased ETA receptors in the renal vascular tissue when compared with control mice. KEY RESULTS: In response to PKC stimulation, reactive oxygen species production by isolated glomeruli from HbSS sickle mice was increased compared with that from HbSA controls, an effect that was prevented by 1 week in vivo treatment with the selective ETA antagonist, ABT-627. Protein and nephrin excretion were both elevated in sickle mice, effects that were also significantly attenuated by ABT-627. Finally, ETA receptor antagonism caused a significant reduction in mRNA expression of NADPH oxidase subunits, which may contribute to nephropathy in sickle cell disease. CONCLUSIONS AND IMPLICATIONS: These data support a novel role for ET-1 in the progression of sickle nephropathy, specifically via the ETA receptor, and suggest a potential role for ETA receptor antagonism in a treatment strategy. PMID- 26561981 TI - One Size Does Not Fit All--Regional Variation in the Impact of the Share 35 Liver Allocation Policy. AB - Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre-Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post-Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan-Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End-stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ-perfusion support at transplant post-Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre Share 35 and post-Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post-Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting "sicker patients" with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions. PMID- 26561983 TI - Reply: Respiratory motor function in centronuclear myopathy. PMID- 26561982 TI - Signal recognition particle immunoglobulin g detected incidentally associates with autoimmune myopathy. AB - INTRODUCTION: Paraneoplastic autoantibody screening of 150,000 patient sera by tissue-based immunofluorescence incidentally revealed 170 with unsuspected signal recognition particle (SRP) immunoglobulin G (IgG), which is a recognized biomarker of autoimmune myopathy. Of the 77 patients with available information, 54 had myopathy. We describe the clinical/laboratory associations. METHODS: Distinctive cytoplasm-binding IgG (mouse tissue substrate) prompted western blot, enzyme-linked immunoassay, and immunoprecipitation analyses. Available histories were reviewed. RESULTS: The immunostaining pattern resembled rough endoplasmic reticulum, and mimicked Purkinje-cell cytoplasmic antibody type 1 IgG/anti-Yo. Immunoblotting revealed ribonucleoprotein reactivity. Recombinant antigens confirmed the following: SRP54 IgG specificity alone (17); SRP72 IgG specificity alone (3); both (32); or neither (2). Coexisting neural autoantibodies were identified in 28% (low titer). Electromyography revealed myopathy with fibrillation potentials; 78% of biopsies had active necrotizing myopathy with minimal inflammation, and 17% had inflammatory myopathy. Immunotherapy responsiveness was typically slow and incomplete, and relapses were frequent on withdrawal. Histologically confirmed cancers (17%) were primarily breast and hematologic, with some others. CONCLUSIONS: Autoimmune necrotizing SRP myopathy, both idiopathic and paraneoplastic, is underdiagnosed in neurological practice. Serological screening aids early diagnosis. Cancer surveillance and appropriate immunosuppressant therapy may improve outcome. Muscle Nerve 53: 925-932, 2016. PMID- 26561984 TI - Mapping the Topography of a Protein Energy Landscape. AB - Protein energy landscapes are highly complex, yet the vast majority of states within them tend to be invisible to experimentalists. Here, using site-directed mutagenesis and exploiting the simplicity of tandem-repeat protein structures, we delineate a network of these states and the routes between them. We show that our target, gankyrin, a 226-residue 7-ankyrin-repeat protein, can access two alternative (un)folding pathways. We resolve intermediates as well as transition states, constituting a comprehensive series of snapshots that map early and late stages of the two pathways and show both to be polarized such that the repeat array progressively unravels from one end of the molecule or the other. Strikingly, we find that the protein folds via one pathway but unfolds via a different one. The origins of this behavior can be rationalized using the numerical results of a simple statistical mechanics model that allows us to visualize the equilibrium behavior as well as single-molecule folding/unfolding trajectories, thereby filling in the gaps that are not accessible to direct experimental observation. Our study highlights the complexity of repeat-protein folding arising from their symmetrical structures; at the same time, however, this structural simplicity enables us to dissect the complexity and thereby map the precise topography of the energy landscape in full breadth and remarkable detail. That we can recapitulate the key features of the folding mechanism by computational analysis of the native structure alone will help toward the ultimate goal of designed amino-acid sequences with made-to-measure folding mechanisms-the Holy Grail of protein folding. PMID- 26561985 TI - Neutral and adaptive genomic signatures of rapid poleward range expansion. AB - Many species are expanding their range polewards, and this has been associated with rapid phenotypic change. Yet, it is unclear to what extent this reflects rapid genetic adaptation or neutral processes associated with range expansion, or selection linked to the new thermal conditions encountered. To disentangle these alternatives, we studied the genomic signature of range expansion in the damselfly Coenagrion scitulum using 4950 newly developed genomic SNPs and linked this to the rapidly evolved phenotypic differences between core and (newly established) edge populations. Most edge populations were genetically clearly differentiated from the core populations and all were differentiated from each other indicating independent range expansion events. In addition, evidence for genetic drift in the edge populations, and strong evidence for adaptive genetic variation in association with the range expansion was detected. We identified one SNP under consistent selection in four of the five edge populations and showed that the allele increasing in frequency is associated with increased flight performance. This indicates collateral, non-neutral evolutionary changes in independent edge populations driven by the range expansion process. We also detected a genomic signature of adaptation to the newly encountered thermal regimes, reflecting a pattern of countergradient variation. The latter signature was identified at a single SNP as well as in a set of covarying SNPs using a polygenic multilocus approach to detect selection. Overall, this study highlights how a strategic geographic sampling design and the integration of genomic, phenotypic and environmental data can identify and disentangle the neutral and adaptive processes that are simultaneously operating during range expansions. PMID- 26561986 TI - Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches. AB - Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions. PMID- 26561987 TI - Conformational Changes and Association of Membrane-Interacting Peptides in Myelin Membrane Models: A Case of the C-Terminal Peptide of Proteolipid Protein and the Antimicrobial Peptide Melittin. AB - Model membranes composed of various lipid mixtures can segregate into liquid ordered (Lo) and liquid-disordered (Ld) phases. In this study, lipid vesicles composed of mainly Lo or Ld phases as well as complex lipid systems representing the cytosolic leaflet of the myelin membrane were characterized by fluorescence resonance energy transfer with a donor/acceptor pair that preferentially partitioned into Lo or Ld phases, respectively. The fluidity of the lipid systems containing >30% cholesterol was modulated in the presence of the amphipathic peptide melittin. With all the studied lipid systems, melittin attained an alpha helical conformation as determined by CD spectroscopy and attained varying degrees of membrane association and penetration as determined by intrinsic Trp fluorescence. The other protein domain utilized was a putative amphipathic helical peptide derived from the cytosolic C-terminal sequence of proteolipid protein (PLP) which is the most abundant protein in the myelin membrane. The C terminal PLP peptide transitioned from a random coil to an alpha-helix in the presence of trifluoroethanol. Upon interacting with each of lipid vesicle system, the PLP peptide also folded into a helix; however, at high concentrations of the peptide with fluid lipid systems, associated helices transmuted into a beta-sheet conformer. The membrane-associated aggregation of the cytosolic C-termini could be a mechanism by which the transmembrane PLP multimerizes in the myelin membrane. PMID- 26561988 TI - Evolving Roles for Physicians and Genetic Counselors in Managing Complex Genetic Disorders. AB - Proponents of personalized medicine predict that genetic information will provide pivotal perspectives for the prevention and management of complex disorders. Personalized medicine differs from traditional Western medicine, in that it focuses on more complex disorders that require mechanistic disease modeling and outcome simulation by integrating genomic risk, environmental stressors, and biomarkers as indicators of disease state. This information could be useful to guide targeted therapy and prevent pathologic outcomes. However, gaps exist in the process of linking the pieces together; currently, genetic data are seldom used to assist physicians in clinical decision making. With rapid growth in genetic data and the requirements for new paradigms for complex disorders comes the need to train professionals to understand and manage the impact of genetic information on patients within these clinical settings. Here we describe the challenges, controversies, and opportunities for genetics and genetic counselors in managing complex disorders and discuss the rationale for modifications in genetic counselor training and function. We conclude that a major paradigm shift is underway and a compelling functional, ethical, and financial argument can be made for employing properly trained genetic counselors to be strategically positioned within the health-care industries that are responsible for managing complex disorders. PMID- 26561989 TI - Recent Advances in Celiac Disease from TTG to Gluten in Pee. PMID- 26561990 TI - The First Years after Fellowship: Our Perspective. PMID- 26561992 TI - Graphite Screen-Printed Electrodes Applied for the Accurate and Reagentless Sensing of pH. AB - A reagentless pH sensor based upon disposable and economical graphite screen printed electrodes (GSPEs) is demonstrated for the first time. The voltammetric pH sensor utilizes GSPEs which are chemically pretreated to form surface immobilized oxygenated species that, when their redox behavior is monitored, give a Nernstian response over a large pH range (1-13). An excellent experimental correlation is observed between the voltammetric potential and pH over the entire pH range of 1-13 providing a simple approach with which to monitor solution pH. Such a linear response over this dynamic pH range is not usually expected but rather deviation from linearity is encountered at alkaline pH values; absence of this has previously been attributed to a change in the pKa value of surface immobilized groups from that of solution phase species. This non-deviation, which is observed here in the case of our facile produced reagentless pH sensor and also reported in the literature for pH sensitive compounds immobilized upon carbon electrodes/surfaces, where a linear response is observed over the entire pH range, is explained alternatively for the first time. The performance of the GSPE pH sensor is also directly compared with a glass pH probe and applied to the measurement of pH in "real" unbuffered samples where an excellent correlation between the two protocols is observed validating the proposed GSPE pH sensor. PMID- 26561991 TI - The complete mitogenome of a 500-year-old Inca child mummy. AB - In 1985, a frozen mummy was found in Cerro Aconcagua (Argentina). Archaeological studies identified the mummy as a seven-year-old Inca sacrifice victim who lived >500 years ago, at the time of the expansion of the Inca Empire towards the southern cone. The sequence of its entire mitogenome was obtained. After querying a large worldwide database of mitogenomes (>28,000) we found that the Inca haplotype belonged to a branch of haplogroup C1b (C1bi) that has not yet been identified in modern Native Americans. The expansion of C1b into the Americas, as estimated using 203 C1b mitogenomes, dates to the initial Paleoindian settlements (~18.3 thousand years ago [kya]); however, its internal variation differs between Mesoamerica and South America. By querying large databases of control region haplotypes (>150,000), we found only a few C1bi members in Peru and Bolivia (e.g. Aymaras), including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire (Peruvian Andes). Overall, the results suggest that the profile of the mummy represents a very rare sub-clade that arose 14.3 (5 23.6) kya and could have been more frequent in the past. A Peruvian Inca origin for present-day C1bi haplotypes would satisfy both the genetic and paleo anthropological findings. PMID- 26561993 TI - Current concepts of protective ventilation during general anaesthesia. AB - Mechanical ventilation with high tidal volumes (VT) has been common practice in operating theatres because this strategy recruits collapsed lung tissue and improves ventilation-perfusion mismatch, thus decreasing the need for high inspired oxygen concentrations. Positive end-expiratory pressure (PEEP) was not used routinely because it was thought to impair cardiovascular function. Over the past two decades there have been advances in our understanding of the causes and importance of ventilation-induced lung injury based on studies in animals with healthy lungs, and trials in critically ill patients with and without acute respiratory distress syndrome. Recent data from randomised controlled trials in patients receiving ventilation during general anaesthesia for surgery have demonstrated that lung-protective strategies (use of low VT, use of PEEP if indicated, and avoidance of excessive oxygen concentrations) are also of importance during intraoperative ventilation. PMID- 26561994 TI - Porphyromonas gingivalis and Epstein-Barr Virus Are Associated With Increased Levels of Visfatin in Gingival Crevicular Fluid. AB - BACKGROUND: There is little clinical information on the relationship between periodontopathogens and visfatin. The purpose of this study is to determine visfatin levels in the gingival crevicular fluid (GCF) of healthy individuals and patients with periodontitis and to investigate the possible relationship between this adipokine and the presence and levels of Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescense, and Epstein-Barr virus (EBV). METHODS: Eighteen healthy individuals and 27 patients with periodontitis were included in this study. GCF and plaque samples were obtained from all individuals. Visfatin levels were analyzed by enzyme-linked immunosorbent assay, and the bacterial numbers were evaluated by the reverse transcription-polymerase chain reaction method. RESULTS: In patients with periodontitis, the visfatin levels in the GCF (mean: 84.29 ng/mL; range: 63.8 to 108.9 ng/mL) were significantly higher compared with those of the healthy individuals (mean: 38.06 ng/mL; range: 13.8 to 89.02 ng/mL) (P <0.01). There was a positive correlation between the visfatin levels and P. gingivalis (r = 0.266, P <0.05), whereas no correlation was found between visfatin levels and other microorganisms. In addition, the visfatin levels were found to be higher in individuals in whom P. gingivalis was detected than for those without P. gingivalis (P <0.01). The visfatin levels were also found to be higher in individuals in whom EBV was detected (P <0.05). CONCLUSIONS: To the best of the authors' knowledge, the present study is the first one to show the correlation of periodontopathogens and GCF visfatin levels. P. gingivalis colonization of the periodontal pockets may increase visfatin secretion. Furthermore, the presence of EBV in the plaque may be another factor that causes an increase in visfatin levels. PMID- 26561995 TI - Expression of Vascular Endothelial Growth Factor Has a Regulatory Role in Gingival Venules in Experimental Diabetes. AB - BACKGROUND: In the present study, the possible localization and role of vascular endothelial growth factor receptor type 2 (VEGFR2) in the regulation of gingival venules in a rat model of experimental diabetes are examined. METHODS: Six weeks after streptozotocin premedication, Wistar male rats presenting blood sugar levels >20 mmol/L were selected for investigation. The VEGFR2 antagonist ZM323881 [5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methylphenol-hydrochloride] (20 MUg/mL) was dripped onto the gingiva between the mandibular incisors. Changes in diameter of the selected gingival venule were measured by vital microscopy combined with digital photography at specified times. Immunohistochemical staining was used to localize VEGFR2. For controls, the same protocol was used on animals with normal blood sugar levels and healthy gingiva. RESULTS: There was a significant difference between the baseline venule diameter of the diabetic and the control groups (47 +/- 1 and 28 +/- 2 MUm, respectively). After 15, 30, and 60 minutes of local application of ZM323881, significant vasoconstriction was observed in the venules of diabetic rats compared with the baseline (81.4% +/- 4.6%, 81.8% +/- 4.4%, and 80.6% +/- 5.1%, respectively). The control group showed no change in the venule diameter. The immunohistochemical analysis showed significantly increased VEGFR2 expression in the mast cells along the venules in the diabetic group, whereas mast cells were rarely found in the control group. CONCLUSIONS: The findings suggest that VEGF expression is increased in gingiva in experimentally induced diabetes. After VEGFR2 activation, the mast cell-derived vasodilatory and inflammatory mediators may contribute markedly to the concomitant changes in the microcirculation. PMID- 26561996 TI - Implant Abutment Cleaning by Plasma of Argon: 5-Year Follow-Up of a Randomized Controlled Trial. AB - BACKGROUND: Contamination of implant abutments could potentially influence the peri-implant tissue inflammatory response. The aim of the present study is to assess the radiographic bone changes around customized, platform-switched abutments placed according to the "one-abutment-one-time" protocol, with and without plasma of argon cleaning treatment. METHODS: Thirty healthy patients with thin gingival biotype (<1 mm) and history of periodontal disease received one maxillary implant each. Immediately before abutment connection, patients were randomly assigned to control group (cleaning protocol by steaming) or test group (plasma of argon treatment). Outcome measures were: 1) success rate of implants and prostheses; 2) biologic and prosthetic complications; 3) peri-implant marginal bone loss (MBL); 4) esthetic and periodontal parameters; and 5) patient satisfaction. RESULTS: Neither implants nor prostheses were lost in either group at the 5-year follow-up examination. Overall, both groups showed a slight amount of peri-implant bone loss from baseline to 5 years. A statistically higher mean MBL was found in the control group compared with the test group at 6, 24, and 60 months after crown connection. Nevertheless, during the entire follow-up period, intragroup comparison demonstrated statistically significant mean MBL in the control group, but not in the test group. The test group showed a higher mean gain at the soft tissue margin, but not for the papilla. All implants showed good periodontal parameters, with no significant differences between groups. CONCLUSION: Plasma of argon could be used to disinfect implant abutments before insertion to minimize future peri-implant bone resorption. PMID- 26561997 TI - Use of Platelet-Rich Fibrin Membrane in the Treatment of Gingival Recession: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The aim of this systematic review is to evaluate the effects of platelet-rich fibrin (PRF) membranes on the outcomes of clinical treatments in patients with gingival recession. METHODS: Articles that were published before June 2015 were searched electronically in four databases without any date or language restrictions and searched manually in regular journals and unpublished studies. The eligibility criteria comprised randomized controlled trials (RCTs) and prospective controlled trials with follow-up periods of >= 6 months that compared the performance of PRF to other biomaterials in the treatment of Miller Class I or II gingival recessions. For the meta-analysis, the inverse variance method was used in fixed- or random-effect models, which were chosen according to heterogeneity. The estimates of the intervention effects were expressed as the mean differences in percentages or millimeters. RESULTS: Six RCTs and one prospective clinical trial are included in this review. Root coverage (RC) and clinical attachment level (CAL) did not differ significantly between the analyzed subgroups (P = 0.57 and P = 0.50, respectively). The keratinized mucosa width (KMW) gain was significantly greater (P = 0.04) in the subgroup that was treated with connective tissue grafts. CONCLUSION: The results of the meta-analysis suggest that the use of PRF membranes did not improve the RC, KMW, or CAL of Miller Class I and II gingival recessions compared with the other treatment modalities. PMID- 26561998 TI - The Effects of Initial Periodontal Therapy on the Serum Receptor Activator of Nuclear Factor-kappabeta Ligand/Osteoprotegerin System in Patients With Type 2 Diabetes Mellitus and Periodontitis. AB - BACKGROUND: The aim of the present study is to evaluate the serum receptor activator of nuclear factor-kappabeta ligand (RANKL)/osteoprotegerin (OPG) system in patients with chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM) and its changes after periodontal intervention. METHODS: Thirty-five patients with CP + T2DM, 35 systemically healthy patients with CP, and 35 healthy controls were enrolled, and serum levels of RANKL and OPG were measured at baseline. Then the CP + T2DM group was divided into a well-controlled subgroup and a poorly controlled subgroup according to their hemoglobin A1c (HbA1c), and initial periodontal therapy was performed. After 3 months, patients in both subgroups were recalled, and serum RANKL and OPG levels were tested again and compared with the baseline. RESULTS: At baseline, serum levels of OPG in the T2DM + CP group were much lower than in the CP group and healthy controls (197.41 +/- 57.05 pg/mL versus 232.60 +/- 70.85 pg/mL [CP group] or 244.96 +/- 85.13 pg/mL [healthy controls], P <0.05), whereas their RANKL levels were much higher than in the other two groups (324.35 +/- 87.62 pg/mL versus 284.52 +/- 90.35 pg/mL [CP group] or 163.01 +/- 45.24 pg/mL [healthy control], P <0.05), as was the RANKL/OPG (R/O) ratio (1.68 +/- 0.33 versus 1.26 +/- 0.35 [CP group] or 0.72 +/- 0.25 [healthy control], P <0.001). Serum levels of OPG in both disease groups had significant negative correlations with HbA1C, and serum levels of RANKL in all participants had significant positive correlations with periodontal parameters. After periodontal intervention, both the well-controlled and poorly controlled subgroups exhibited significant increases in OPG and decreases in RANKL in serum, and the R/O ratio was also notably reduced. Additionally, the poorly controlled subgroup exhibited a greater reduction in HbA1c and a greater increase in OPG than the well-controlled subgroup. CONCLUSIONS: The changing trend in the serum RANKL/OPG system in patients with T2DM + CP was similar to that seen in CP patients and may be even more pronounced. Periodontal intervention effectively improved glucose metabolism and changed the serum RANKL/OPG system regardless of whether patients' HbA1c was well-controlled or poorly controlled over the 3-month observation period. PMID- 26561999 TI - A Familial Pattern of Multiple Idiopathic Cervical Root Resorption With a 30-Year Follow-Up. AB - BACKGROUND: Multiple idiopathic cervical root resorption (MICRR) is a rare entity distinct from pathologic root resorption that occurs as a result of several local and systemic factors. METHODS: This report describes a familial pattern of MICRR, including a recently identified case and a 30-year follow-up on previously described cases. RESULTS: The previously reported father (aged 95 years) and son (aged 64 years), and the recently affected daughter (aged 61 years) recounted non contributory medical history. The resorptive lesions were asymptomatic, unassociated with any predisposing factors, and first identified during the fourth to sixth decades of life. All tooth types were affected, with posterior teeth being affected earlier and with greater frequency; however, distal root surfaces were never affected. The resorptive lesions were progressive in nature, with additional teeth becoming involved as the condition was followed over time. In many instances, surrounding alveolar bone extended into the existing resorptive defects, but without clinical evidence of ankylosis. Gingival tissues, periodontal probing, and tooth mobility were within normal limits. Microcomputed tomography of extracted teeth demonstrated that the lesions were more extensive than clinically evident and rarely invaded the pulp chamber. Histologically, many resorptive lesions were noted along the cementum surface, with evidence of isolated cemental repair. Management of MICRR focused on restoring damaged root surfaces and extracting teeth with extensive root resorption. CONCLUSIONS: MICRR is a challenging entity with unknown etiology and a lack of well-established preventive and management strategies. The familial pattern noted in this report necessitates future studies to investigate the role of genetic components in MICRR development. PMID- 26562000 TI - Obstructive sleep apnea and cancer: effects of intermittent hypoxia? AB - Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment. PMID- 26562001 TI - Does running strengthen bone? AB - Bone is a living tissue needing mechanical stress to maintain strength. Traditional endurance exercises offer only modest effects on bone. Walking and running produce low impact but lead to bone fatigue. This article is specifically addressed to therapists and explains the mechanisms involved for the effects of exercise on bone. Intermittent exercise limits bone fatigue, and downhill exercises increase ground impact forces and involve eccentric muscle contractions, which are particularly osteogenic. PMID- 26562002 TI - Behavioral Bias for Food Reflected in Hand Movements: A Preliminary Study with Healthy Subjects. AB - Palatable food induces general approach tendencies when compared to nonfood stimuli. For eating disorders, the modification of an attention bias toward food was proposed as a treatment option. Similar approaches have been efficient for other psychiatric conditions and, recently, successfully incorporated approach motivation. The direct impact of attentional biases on spontaneous natural behavior has hardly been investigated so far, although actions may serve as an intervention target, especially seeing the recent advances in the field of embodied cognition. In this study, we addressed the interplay of motor action execution and cognition when interacting with food objects. In a Virtual Reality (VR) setting, healthy participants repeatedly grasped or warded high-calorie food or hand-affordant ball objects using their own dominant hand. This novel experimental paradigm revealed an attention-like bias in hand-based actions: 3D objects of food were collected faster than ball objects, and this difference correlated positively with both individual body mass index and diet-related attitudes. The behavioral bias for food in hand movements complements several recent experimental and neurophysiological findings. Implications for the use of VR in the treatment of eating-related health problems are discussed. PMID- 26562003 TI - The Effect of Head Massage on the Regulation of the Cardiac Autonomic Nervous System: A Pilot Randomized Crossover Trial. AB - OBJECTIVES: To evaluate the effect of a single 10-minute session of Chinese head massage on the activity of the cardiac autonomic nervous system via measurement of heart rate variability (HRV). DESIGN: In this pilot randomized crossover trial, each participant received both head massage and the control intervention in a randomized fashion. SETTINGS/LOCATION: The study was conducted at Children's & Women's Health Centre of British Columbia between June and November 2014. PARTICIPANTS: Ten otherwise healthy adults (6 men and 4 women) were enrolled in this study. INTERVENTIONS: The intervention comprised 10 minutes of head massage therapy (HMT) in a seated position compared with a control intervention of sitting quietly on the same chair with eyes closed for an equal amount of time (no HMT). OUTCOME MEASURES: The primary outcome measures were the main parameters of HRV, including total power (TP), high frequency (HF), HF as a normalized unit, pre-ejection period, and heart rate (HR). RESULTS: A single short session (10 minutes) of head massage demonstrated an increase in TP continuing up to 20 minutes after massage and reaching statistical significance at 10 minutes after massage (relative change from baseline, 66% for HMT versus -6.6% for no HMT; p = 0.017). The effect on HF also peaked up to 10 minutes after massage (59.4% for HMT versus 4% for no HMT; p = 0.139). Receiving head massage also decreased HR by more than three-fold compared to the control intervention. CONCLUSION: This study shows the potential benefits of head massage by modulating the cardiac autonomic nervous system through an increase in the total variability and a shift toward higher parasympathetic nervous system activity. Randomized controlled trials with larger sample size and multiple sessions of massage are needed to substantiate these findings. PMID- 26562004 TI - Effectiveness and acceptability of parental financial incentives and quasi mandatory schemes for increasing uptake of vaccinations in preschool children: systematic review, qualitative study and discrete choice experiment. AB - BACKGROUND: Uptake of preschool vaccinations is less than optimal. Financial incentives and quasi-mandatory policies (restricting access to child care or educational settings to fully vaccinated children) have been used to increase uptake internationally, but not in the UK. OBJECTIVE: To provide evidence on the effectiveness, acceptability and economic costs and consequences of parental financial incentives and quasi-mandatory schemes for increasing the uptake of preschool vaccinations. DESIGN: Systematic review, qualitative study and discrete choice experiment (DCE) with questionnaire. SETTING: Community, health and education settings in England. PARTICIPANTS: Qualitative study - parents and carers of preschool children, health and educational professionals. DCE - parents and carers of preschool children identified as 'at high risk' and 'not at high risk' of incompletely vaccinating their children. DATA SOURCES: Qualitative study - focus groups and individual interviews. DCE - online questionnaire. REVIEW METHODS: The review included studies exploring the effectiveness, acceptability or economic costs and consequences of interventions that offered contingent rewards or penalties with real material value for preschool vaccinations, or quasi-mandatory schemes that restricted access to 'universal' services, compared with usual care or no intervention. Electronic database, reference and citation searches were conducted. RESULTS: Systematic review - there was insufficient evidence to conclude that the interventions considered are effective. There was some evidence that the quasi-mandatory interventions were acceptable. There was insufficient evidence to draw conclusions on economic costs and consequences. Qualitative study - there was little appetite for parental financial incentives. Quasi-mandatory schemes were more acceptable. Optimising current services was consistently preferred to the interventions proposed. DCE and questionnaire - universal parental financial incentives were preferred to quasi-mandatory interventions, which were preferred to targeted incentives. Those reporting that they would need an incentive to vaccinate their children completely required around L110. Those who did not felt that the maximum acceptable incentive was around L70. LIMITATIONS: Systematic review - a number of relevant studies were excluded as they did not meet the study design inclusion criteria. Qualitative study - few partially and non-vaccinating parents were recruited. DCE and questionnaire - data were from a convenience sample. CONCLUSIONS: There is little current evidence on the effectiveness or economic costs and consequences of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Universal incentives are likely to be more acceptable than targeted ones. Preferences concerning incentives versus quasi-mandatory interventions may depend on the context in which these are elicited. FUTURE WORK: Further evidence is required on (i) the effectiveness and optimal configuration of parental financial incentive and quasi-mandatory interventions for preschool vaccinations if effectiveness is confirmed, further evidence is required on how to communicate this to stakeholders and the impact on acceptability; and (ii) the acceptability of parental financial incentive and quasi-mandatory interventions for preschool vaccinations to members of the population who are not parents of preschool children or relevant health professionals. Further consideration should be given to (i) incorporating reasons for non-vaccination into new interventions for promoting vaccination uptake; and (ii) how existing services can be optimised. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003192. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26562005 TI - Estimation of diffusion properties in three-way fiber crossings without overfitting. AB - Diffusion-weighted magnetic resonance imaging permits assessment of the structural integrity of the brain's white matter. This requires unbiased and precise quantification of diffusion properties. We aim to estimate such properties in simple and complex fiber geometries up to three-way fiber crossings using rank-2 tensor model selection. A maximum a-posteriori (MAP) estimator is employed to determine the parameters of a constrained triple tensor model. A prior is imposed on the parameters to avoid the degeneracy of the model estimation. This prior maximizes the divergence between the three tensor's principal orientations. A new model selection approach quantifies the extent to which the candidate models are appropriate, i.e. a single-, dual- or triple tensor model. The model selection precludes overfitting to the data. It is based on the goodness of fit and information complexity measured by the total Kullback Leibler divergence (ICOMP-TKLD). The proposed framework is compared to maximum likelihood estimation on phantom data of three-way fiber crossings. It is also compared to the ball-and-stick approach from the FMRIB Software Library (FSL) on experimental data. The spread in the estimated parameters reduces significantly due to the prior. The fractional anisotropy (FA) could be precisely estimated with MAP down to an angle of approximately 40 degrees between the three fibers. Furthermore, volume fractions between 0.2 and 0.8 could be reliably estimated. The configurations inferred by our method corresponded to the anticipated neuro anatomy both in single fibers and in three-way fiber crossings. The main difference with FSL was in single fiber regions. Here, ICOMP-TKLD predominantly inferred a single fiber configuration, as preferred, whereas FSL mostly selected dual or triple order ball-and-stick models. The prior of our MAP estimator enhances the precision of the parameter estimation, without introducing a bias. Additionally, our model selection effectively balances the trade-off between the goodness of fit and information complexity. The proposed framework can enhance the sensitivity of statistical analysis of diffusion tensor MRI. PMID- 26562006 TI - Synthesis of ceria based superhydrophobic coating on Ni20Cr substrate via cathodic electrodeposition. AB - In this work, superhydrophobic cerium oxide coating surface (111) with dual scale texture on Ni20Cr substrate is obtained by combination of electropolishing the substrate and subsequent cathodic electrodeposition and long-term UVH surface relaxation. To form hierarchical structures of CeO2 is controllable by varying the substrate roughness, and electropolishing period. The results indicated that at the optimal condition, the surface of the cerium oxide coating showed a superhydrophobicity with a great water contact angle (151.0 +/- 1.4 degrees ) with Gecko state. An interface model for electropolishing of substrate surface in cerium nitrate medium is proposed. We expect that this facile process can be readily and widely adopted for the design of superhydrophobic coating on engineering materials. PMID- 26562008 TI - [Aesthetic/Plastic Surgery in Children as Seen from the Perspective of Child and Adolescent Psychiatry and Psychotherapy]. AB - Physical deformities may cause psychological stress and lead to psychological disorders in children and adolescents. On the other hand, the correction of non pathological conditions is a legal issue in patients unable to consent, a group that is partly made up of minors. This article provides an overview on available evidence on the psychological consequences of physical deformities, psychiatric contraindications for plastic surgery due to psychological disorders, and on the issue of minors' ability to consent. PMID- 26562009 TI - [Microsurgical Autologous Lymph Vessel Transplantation: Does Harvesting Lymphatic Vessel Grafts Induce Lymphatic Transport Disturbances in the Donor Limb?]. AB - OBJECTIVE: The aim of this study was to determine whether the extirpation of lymphatic vessels induces lymphatic transport disturbances in the donor limb of patients following the harvest of lymph vessel grafts. PATIENTS, MATERIAL AND METHODS: A total of 19 consecutive patients (15 females, 4 males; mean age 51.5 years, range 21.8-72.3) were examined by lymphoscintigraphy before and after surgery. The patients had previously been diagnosed with upper or lower limb lymphoedema in accordance with the criteria of the International Society of Lymphology, and autologous lymph vessel transplantation had been intended for treatment. Since only patients with normal scintigraphic tests at the harvesting site were considered for treatment, all consecutive patients (n=19) had normal scintigraphic tests of the donor limb prior to surgery. In order to quantify the visual scintigraphic findings, a well established numeric transport index (TI) was used, which combined 5 visual parameters of transport kinetics. To that end, the following visually assessed criteria were evaluated: temporal and spatial kinetics, radiopharmaceutical distribution pattern, time to appearance of inguinal lymph nodes, qualitative visualisation of lymph nodes and lymph vessels. RESULTS: All patients underwent a preoperative scintigraphic baseline study and a postoperative scintigraphic follow-up after autologous lymphatic vessel grafting. The mean time period from the baseline study to the date of microsurgical lymph vessel transplantation was 3.5 months (median 2.5 months). The scintigraphic follow-up was performed 48.6 months (median 57.8 months) following transplantation. In all patients the postoperative TI was very close to the TI calculated in the preoperative baseline scintigraphy, and all TIs were within the normal range (TI<10). The absolute value of deviation of pre- vs. post-operative transport indices was calculated to be 0.2 on average (maximum 0.4). CONCLUSIONS: The results show that microsurgical transfer of lymph vessel grafts is possible without compromising lymphatic drainage of the donor limb if safety precautions are taken into account. PMID- 26562010 TI - A FRET-based ratiometric two-photon fluorescent probe for dual-channel imaging of nitroxyl in living cells and tissues. AB - A FRET-based two-photon fluorescent probe, , which exhibited a fast and high selective ratiometric response to nitroxyl, was first proposed. was successfully applied to two-photon dual-channel imaging of nitroxyl in living cells and tissues with less cross-talk between channels and satisfactory deep-tissue imaging depth. PMID- 26562011 TI - Interferon-gamma Inhibits Ebola Virus Infection. AB - Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID- 26562012 TI - Heterologous Expression of Mannanase and Developing a New Reporter Gene System in Lactobacillus casei and Escherichia coli. AB - Reporter gene systems are useful for studying bacterial molecular biology, including the regulation of gene expression and the histochemical analysis of protein products. Here, two genes, beta-1,4-mannanase (manB) from Bacillus pumilus and beta-glucuronidase (gusA) from Escherichia coli K12, were cloned into the expression vector pELX1. The expression patterns of these reporter genes in Lactobacillus casei were investigated by measuring their enzymatic activities and estimating their recombinant protein yields using western blot analysis. Whereas mannanase activity was positively correlated with the accumulation of ManB during growth, GusA activity was not; western blot analysis indicated that while the amount of GusA protein increased during later growth stages, GusA activity gradually decreased, indicating that the enzyme was inactive during cell growth. A similar trend was observed in E. coli JM109. We chose to use the more stable mannanase gene as the reporter to test secretion expression in L. casei. Two pELX1-based secretion vectors were constructed: one carried the signal peptide of the unknown secretion protein Usp45 from Lactococcus lactis (pELSH), and the other contained the full-length SlpA protein from the S-layer of L. acidophilus (pELWH). The secretion of ManB was detected in the supernatant of the pELSH-ManB transformants and in the S-layer of the cell surface of the pELWH-ManB transformants. This is the first report demonstrating that the B. pumilus manB gene is a useful reporter gene in L. casei and E.coli. PMID- 26562013 TI - Optimizing the Detection of Wakeful and Sleep-Like States for Future Electrocorticographic Brain Computer Interface Applications. AB - Previous studies suggest stable and robust control of a brain-computer interface (BCI) can be achieved using electrocorticography (ECoG). Translation of this technology from the laboratory to the real world requires additional methods that allow users operate their ECoG-based BCI autonomously. In such an environment, users must be able to perform all tasks currently performed by the experimenter, including manually switching the BCI system on/off. Although a simple task, it can be challenging for target users (e.g., individuals with tetraplegia) due to severe motor disability. In this study, we present an automated and practical strategy to switch a BCI system on or off based on the cognitive state of the user. Using a logistic regression, we built probabilistic models that utilized sub-dural ECoG signals from humans to estimate in pseudo real-time whether a person is awake or in a sleep-like state, and subsequently, whether to turn a BCI system on or off. Furthermore, we constrained these models to identify the optimal anatomical and spectral parameters for delineating states. Other methods exist to differentiate wake and sleep states using ECoG, but none account for practical requirements of BCI application, such as minimizing the size of an ECoG implant and predicting states in real time. Our results demonstrate that, across 4 individuals, wakeful and sleep-like states can be classified with over 80% accuracy (up to 92%) in pseudo real-time using high gamma (70-110 Hz) band limited power from only 5 electrodes (platinum discs with a diameter of 2.3 mm) located above the precentral and posterior superior temporal gyrus. PMID- 26562014 TI - The Metabolomic Profile of Spent Culture Media from Day-3 Human Embryos Cultured under Low Oxygen Tension. AB - Despite efforts made to improve the in vitro embryo culture conditions used during assisted reproduction procedures, human embryos must adapt to different in vitro oxygen concentrations and the new metabolic milieu provided by the diverse culture media used for such protocols. It has been shown that the embryo culture environment can affect not only cellular metabolism, but also gene expression in different species of mammalian embryos. Therefore we wanted to compare the metabolic footprint left by human cleavage-stage embryos under two types of oxygen atmospheric culture conditions (6% and 20% O2). The spent culture media from 39 transferred and implanted embryos from a total of 22 patients undergoing egg donation treatment was analyzed; 23 embryos came from 13 patients in the 6% oxygen concentration group, and 16 embryos from 9 patients were used in the 20% oxygen concentration group. The multivariate statistics we used in our analysis showed that human cleavage-stage embryos grown under both types of oxygen concentration left a similar metabolic fingerprint. We failed to observe any change in the net depletion or release of relevant analytes, such as glucose and especially fatty acids, by human cleavage-stage embryos under either type of culture condition. Therefore it seems that low oxygen tension during embryo culture does not alter the global metabolism of human cleavage-stage embryos. PMID- 26562016 TI - Generating Evidence to Improve the Response to Neglected Diseases: How Operational Research in a Medecins Sans Frontieres Buruli Ulcer Treatment Programme Informed International Management Guidance. PMID- 26562015 TI - Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics. AB - BACKGROUND: The human immunodeficiency virus 1 (HIV-1) epidemic in China historically stemmed from intravenous drug users (IDUs) in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV)/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan. METHODS: Blood samples of 432 HIV-1/HCV co infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed. RESULTS: Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293), 3a (21.8%, 64/293), 6n (14.0%, 41/293), 1b (10.6%, 31/293), 1a (8.2%, 24/293), 6a (5.1%, 15/293) and 6u (2.4%, 7/293). The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong) and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan) bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35*10-4 and 2.38*10-3 substitutions site 1 year-1) and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6), suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A) to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs)-naive IDUs. CONCLUSION: This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and evolution of HCV in IDUs and are valuable for developing HCV prevention and management strategies for this population. PMID- 26562017 TI - Trunk Muscle Activation at the Initiation and Braking of Bilateral Shoulder Flexion Movements of Different Amplitudes. AB - The aim of this study was to investigate if trunk muscle activation patterns during rapid bilateral shoulder flexions are affected by movement amplitude. Eleven healthy males performed shoulder flexion movements starting from a position with arms along sides (0 degrees ) to either 45 degrees , 90 degrees or 180 degrees . EMG was measured bilaterally from transversus abdominis (TrA), obliquus internus (OI) with intra-muscular electrodes, and from rectus abdominis (RA), erector spinae (ES) and deltoideus with surface electrodes. 3D kinematics was recorded and inverse dynamics was used to calculate the reactive linear forces and torque about the shoulders and the linear and angular impulses. The sequencing of trunk muscle onsets at the initiation of arm movements was the same across movement amplitudes with ES as the first muscle activated, followed by TrA, RA and OI. All arm movements induced a flexion angular impulse about the shoulders during acceleration that was reversed during deceleration. Increased movement amplitude led to shortened onset latencies of the abdominal muscles and increased level of activation in TrA and ES. The activation magnitude of TrA was similar in acceleration and deceleration where the other muscles were specific to acceleration or deceleration. The findings show that arm movements need to be standardized when used as a method to evaluate trunk muscle activation patterns and that inclusion of the deceleration of the arms in the analysis allow the study of the relationship between trunk muscle activation and direction of perturbing torque during one and the same arm movement. PMID- 26562018 TI - A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy. AB - OBJECTIVE: We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin. DESIGN: Cohort study of adult patients on ART. SETTING: GHESKIO Clinic in Port-au-Prince, Haiti. PARTICIPANTS: 4,717 ART naive adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008. MAIN OUTCOME MEASURE: Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin. RESULTS: In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30-2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used. CONCLUSIONS: If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted. PMID- 26562019 TI - Seasonal Shifts in Diet and Gut Microbiota of the American Bison (Bison bison). AB - North American bison (Bison bison) are becoming increasingly important to both grassland management and commercial ranching. However, a lack of quantitative data on their diet constrains conservation efforts and the ability to predict bison effects on grasslands. In particular, we know little about the seasonality of the bison diet, the degree to which bison supplement their diet with eudicots, and how changes in diet influence gut microbial communities, all of which play important roles in ungulate performance. To address these knowledge gaps, we quantified seasonal patterns in bison diet and gut microbial community composition for a bison herd in Kansas using DNA sequencing-based analyses of both chloroplast and microbial DNA contained in fecal matter. Across the 11 sampling dates that spanned 166 days, we found that diet shifted continuously over the growing season, allowing bison to take advantage of the seasonal availability of high-protein plant species. Bison consumed more woody shrubs in spring and fall than in summer, when forb and grass intake predominated. In examining gut microbiota, the bacterial phylum Tenericutes shifted significantly in relative abundance over the growing season. This work suggests that North American bison can continuously adjust their diet with a high reliance on non grasses throughout the year. In addition, we find evidence for seasonal patterns in gut community composition that are likely driven by the observed dietary changes. PMID- 26562021 TI - Correction: DAPIT Over-Expression Modulates Glucose Metabolism and Cell Behaviour in HEK293T Cells. PMID- 26562020 TI - SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients. AB - Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point of interest as indicator of therapy options and treatment response in clinical cancer research. Especially patient- and tumor-specific single nucleotide variants that accurately distinguish tumor DNA from wild type DNA are promising targets. The reliable detection and quantification of these single-base DNA variants is technically challenging. Currently, a variety of techniques is applied, with no apparent "gold standard". Here we present a novel qPCR protocol that meets the conditions of extreme sensitivity and specificity that are required for detection and quantification of tumor DNA. By consecutive application of two polymerases, one of them designed for extreme base specificity, the method reaches unprecedented sensitivity and specificity. Three qPCR assays were tested with spike-in experiments, specific for point mutations BRAF V600E, PTEN T167A and NRAS Q61L of melanoma cell lines. It was possible to detect down to one copy of tumor DNA per reaction (Poisson distribution), at a background of up to 200 000 wild type DNAs. To prove its clinical applicability, the method was successfully tested on a small cohort of BRAF V600E positive melanoma patients. PMID- 26562022 TI - Quantifying Integrated Proteomic Responses to Iron Stress in the Globally Important Marine Diazotroph Trichodesmium. AB - Trichodesmium is a biogeochemically important marine cyanobacterium, responsible for a significant proportion of the annual 'new' nitrogen introduced into the global ocean. These non-heterocystous filamentous diazotrophs employ a potentially unique strategy of near-concurrent nitrogen fixation and oxygenic photosynthesis, potentially burdening Trichodesmium with a particularly high iron requirement due to the iron-binding proteins involved in these processes. Iron availability may therefore have a significant influence on the biogeography of Trichodesmium. Previous investigations of molecular responses to iron stress in this keystone marine microbe have largely been targeted. Here a holistic approach was taken using a label-free quantitative proteomics technique (MSE) to reveal a sophisticated multi-faceted proteomic response of Trichodesmium erythraeum IMS101 to iron stress. Increased abundances of proteins known to be involved in acclimation to iron stress and proteins known or predicted to be involved in iron uptake were observed, alongside decreases in the abundances of iron-binding proteins involved in photosynthesis and nitrogen fixation. Preferential loss of proteins with a high iron content contributed to overall reductions of 55-60% in estimated proteomic iron requirements. Changes in the abundances of iron-binding proteins also suggested the potential importance of alternate photosynthetic pathways as Trichodesmium reallocates the limiting resource under iron stress. Trichodesmium therefore displays a significant and integrated proteomic response to iron availability that likely contributes to the ecological success of this species in the ocean. PMID- 26562024 TI - Identification of BRAF Kinase Domain Duplications Across Multiple Tumor Types and Response to RAF Inhibitor Therapy. PMID- 26562023 TI - Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles. AB - The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without gamma-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance. PMID- 26562025 TI - Perlecan Diversely Regulates the Migration and Proliferation of Distinct Cell Types in vitro. AB - Perlecan is a multifunctional component of the extracellular matrix. It shows different effects on distinct cell types, and therefore it is thought to show potential for therapies targeting multiple cell types. However, the full range of multifunctionality of perlecan remains to be elucidated. We cultured various cell types, which were derived from epithelial/endothelial, connective and muscle tissues, in the presence of either antiserum against perlecan or exogenous perlecan, and examined the effects of perlecan on cell migration and proliferation. Cell migration was determined using a scratch assay. Blocking of perlecan by anti-perlecan antiserum inhibited the migration of vascular endothelial cells (VECs) and bone marrow-derived mesenchymal stem cells, and exogenous perlecan added to the culture medium promoted the migration of these cell types. The migration of other cell types was inhibited or was not promoted by exogenous perlecan. Cell proliferation was measured using a water-soluble tetrazolium dye. When cells were cultured at low densities, perlecan blocking inhibited the proliferation of VECs, and exogenous perlecan promoted the proliferation of keratinocytes. In contrast, the proliferation of fibroblasts, pre-adipocytes and vascular smooth muscle cells cultured at low densities was inhibited by exogenous perlecan. When cells were cultured at high densities, perlecan blocking promoted the proliferation of most cell types, with the exception of skeletal system-derived cells (chondrocytes and osteoblasts), which were inhibited by exogenous perlecan. Our results provide an overview of the multiple functions of perlecan in various cell types, and implicate a potential role of perlecan to inhibit undesirable activities, such as fibrosis, obesity and intimal hyperplasia. PMID- 26562026 TI - Possible Gender-Related Modulation by the ROCK1 Gene in Colorectal Cancer Susceptibility. AB - AIM: In view of accumulating evidence supporting a pivotal role of the Rho/ROCK pathway in cancer, we investigated Rho-kinase polymorphisms as potential susceptibility factors in colorectal cancer (CRC) in a representative sample of the Italian population. METHODS: DNA obtained from the peripheral blood samples of 137 CRC patients and 141 healthy controls was genotyped for four ROCK1 (rs35996865; rs73963110; rs2127958; rs288980) and five ROCK2 (rs12692437; rs7563468; rs35768389; rs17463896; rs16857265) selected single nucleotide polymorphisms. RESULTS: None of the allelic variants of the nine selected markers was associated with the occurrence of CRC or with the development of regional lymph node metastasis. By contrast, the ROCK1 rs35996865 G variant allele was significantly more frequent in male patients (p = 0.028) than in the control group. CONCLUSION: This finding is, at present, the first that points to a possible gender-related modulation by the ROCK1 gene in CRC susceptibility. PMID- 26562027 TI - CD10 Immunohistochemical Expression in Apocrine Lesions of the Breast. AB - OBJECTIVE: In the breast, CD10 is expressed by myoepithelial cells (MECs), and apocrine metaplasia has also been mentioned as being positive with this marker. Apocrine lesions have been explored for the expression of CD10. METHODS: The apocrine lesions studied included 11 cysts, 6 cases of apocrine adenosis, 2 of apocrine metaplasia or hyperplasia in papilloma, 13 ductal carcinomas in situ (DCIS) and invasive carcinomas (14 ductal and 4 lobular). RESULTS: Benign apocrine lesions showed complete or partial luminal CD10 staining, although most cases included parts without staining, and 2 lesions were completely negative. The MECs were often but not always positive. Nine of the 13 cases of apocrine DCIS displayed no luminal staining, but 4 demonstrated very focal luminal positivity. The MECs around the DCIS showed a spectrum of staining from nil to strong and complete. Only 4 invasive carcinomas demonstrated luminal/membranous staining. Cytoplasmic CD10 positivity was seen focally in 4 invasive cancers and in 3 DCIS. CONCLUSION: CD10 positivity is luminal/membranous in most benign apocrine lesions, the staining being nonuniversal and sometimes focal. Analogous staining in apocrine malignancies seems rarer in DCIS and even rarer in invasive apocrine carcinomas, but atypical cytoplasmic positivity may also occur. CD10 is not an ideal myoepithelial marker in apocrine lesions. PMID- 26562028 TI - A preliminary study of paraoxonase-1 in infected patients with an indwelling central venous catheter. AB - OBJECTIVES: Identification of biochemical markers to diagnose bloodstream infections in patients with a central venous catheter (CVC) inserted is an active research pursuit. Paraoxonase-1 (PON1) is an enzyme participating in the innate immune system protecting against toxic substances and infectious agents. We investigated the relationships between serum PON1 alterations and the characteristics of infection in a group of patients with a CVC implant. METHODS: Patients (n=114) who had had an inserted CVC removed because of infection or because the usefulness was at an end, and 407 healthy volunteers were recruited. In all participants we measured serum PON1 lactonase and paraoxonase activities, PON1 concentration and genetic polymorphisms, together with levels of the chemokine (C-C motif) ligand 2 (CCL2), procalcitonin and C-reactive protein (CRP). RESULTS: Patients with an acute concomitant infection (ACI) had higher CCL2, CRP and procalcitonin concentrations than the control group, together with lower paraoxonase and lactonase activities and specific activities. The areas under the curve of the receiver operating characteristic plots for paraoxonase and lactonase specific activities in the discrimination between patients with or without and ACI were 0.81 (0.73-0.89) and 0.81 (0.71-0.89), respectively, indicating the high diagnostic accuracy of these parameters. CONCLUSION: This preliminary study suggests that the measurement of PON1 may be useful as a tool for the diagnosis of ACI in patients with an indwelling CVC. PMID- 26562029 TI - Sodium interference in the determination of urinary aldosterone. AB - OBJECTIVES: Primary hyperaldosteronism (PHA) is one of the most common endocrine forms of secondary hypertension. Among the most used confirmatory tests for PHA is urinary aldosterone determination after oral sodium loading test. The primary aim of our study was to investigate if sodium concentrations interfere with urinary aldosterone in an automated competitive immunoassay (Liaison(r)) as well as to verify the manufacturer's specifications. DESIGN AND METHODS: 24-hr urine samples were collected and stored frozen until assayed. Two pools at low and high aldosterone concentrations were prepared. Verification of performance for precision was tested according to Clinical and Laboratory Standards Institute (CLSI) document EP15-A2 and interference with increasing concentrations of NaCl according to CLSI EP7-A2. RESULTS: The assay met the quality specifications according to optimal biological variation. Our results show that sodium concentrations up to 200mmol/L do not interfere on urinary aldosterone quantification, but sodium concentrations above 486mmol/L negatively interfere with the test. CONCLUSIONS: The Liaison(r) automated method is useful for aldosterone determination in the PHA confirmatory test, but interferences with NaCl may occur. It is therefore recommended to determine urinary NaCl before measuring urinary aldosterone to avoid falsely low results. PMID- 26562030 TI - Artificial algae algorithm with multi-light source for numerical optimization and applications. AB - Artificial algae algorithm (AAA), which is one of the recently developed bio inspired optimization algorithms, has been introduced by inspiration from living behaviors of microalgae. In AAA, the modification of the algal colonies, i.e. exploration and exploitation is provided with a helical movement. In this study, AAA was modified by implementing multi-light source movement and artificial algae algorithm with multi-light source (AAAML) version was established. In this new version, we propose the selection of a different light source for each dimension that is modified with the helical movement for stronger balance between exploration and exploitation. These light sources have been selected by tournament method and each light source are different from each other. This gives different solutions in the search space. The best of these three light sources provides orientation to the better region of search space. Furthermore, the diversity in the source space is obtained with the worst light source. In addition, the other light source improves the balance. To indicate the performance of AAA with new proposed operators (AAAML), experiments were performed on two different sets. Firstly, the performance of AAA and AAAML was evaluated on the IEEE-CEC'13 benchmark set. The second set was real-world optimization problems used in the IEEE-CEC'11. To verify the effectiveness and efficiency of the proposed algorithm, the results were compared with other state of-the-art hybrid and modified algorithms. Experimental results showed that the multi-light source movement (MLS) increases the success of the AAA. PMID- 26562031 TI - Stimulus edge effects in the measurement of macular pigment using heterochromatic flicker photometry. AB - Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X , r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point. PMID- 26562032 TI - Characterization of the cellular response triggered by gold nanoparticle-mediated laser manipulation. AB - Laser-based transfection techniques have proven high applicability in several cell biologic applications. The delivery of different molecules using these techniques has been extensively investigated. In particular, new high-throughput approaches such as gold nanoparticle-mediated laser transfection allow efficient delivery of antisense molecules or proteins into cells preserving high cell viabilities. However, the cellular response to the perforation procedure is not well understood. We herein analyzed the perforation kinetics of single cells during resonant gold nanoparticle-mediated laser manipulation with an 850-ps laser system at a wavelength of 532 nm. Inflow velocity of propidium iodide into manipulated cells reached a maximum within a few seconds. Experiments based on the inflow of FM4-64 indicated that the membrane remains permeable for a few minutes for small molecules. To further characterize the cellular response postmanipulation, we analyzed levels of oxidative heat or general stress. Although we observed an increased formation of reactive oxygen species by an increase of dichlorofluorescein fluorescence, heat shock protein 70 was not upregulated in laser-treated cells. Additionally, no evidence of stress granule formation was visible by immunofluorescence staining. The data provided in this study help to identify the cellular reactions to gold nanoparticle-mediated laser manipulation. PMID- 26562033 TI - Immunoassay or LC-MS/MS for the measurement of salivary cortisol in children? AB - BACKGROUND: Dysregulation of the adrenal cortex has been assessed with measurement of salivary cortisol. So far salivary cortisol is routinely measured with immunoassay (IA). However, liquid chromatography-tandem mass spectrometry (MS) is known to offer better specificity. We compared the concentrations of salivary cortisol measured by MS and IA at basal and stress induced conditions and evaluated reasons for the difference in method-dependent cortisol results. METHODS: Saliva samples (n=2703) were collected from 169 children (age range: 8 14 years; 81 healthy children; 55 with internalizing and 33 with externalizing disorders) under circadian conditions and during the Trier Social Stress Test for Children (TSST-C). Biochemical analyses were performed with MS for cortisol and cortisone, IA (IBL, RE62011) for cortisol, and enzyme kinetic assay for alpha amylase. RESULTS: MS and IA showed mostly comparable results for circadian activity and TSST-C response with similar statistical power. However, IA measured cortisol concentrations about 2.39-fold higher than MS. We found that this difference in measured values between MS and IA was mainly due to different standardization of IA compared to MS. In addition, at cortisol IA concentration below 5 nmol/L, cross-reactivity with cortisone was found to contribute to the lower concordance between MS and IA. CONCLUSIONS: Immunoassay and LC-MS/MS were largely comparable in the interpretation of salivary cortisol dynamics in stress research. But the IA method revealed a restricted accuracy in the measuring range below 5 nmol/L. PMID- 26562034 TI - Reference intervals of plasma homoarginine from the German Gutenberg Health Study. AB - BACKGROUND: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk. METHODS: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study. Homoarginine concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Median EDTA plasma homoarginine concentration was 1.88 [25th; 75th percentile, 1.47; 2.41] MUmol/L, with lower concentrations in women (1.77 [1.38; 2.26] MUmol/L) than in men (2.01 [1.61; 2.56] MUmol/L; p<0.001). Sex-specific 2.5th and 97.5th percentiles of reference intervals were 0.84 and 3.89 MUmol/L in women and 0.98 and 4.10 MUmol/L in men, respectively. Homoarginine concentrations also depended on age and single nucleotide polymorphisms related to the L-arginine:glycine amidinotransferase gene. CONCLUSIONS: We provide plasma homoarginine reference intervals in men and women of the general population. The determination of homoarginine levels might be favorable for individual risk stratification. PMID- 26562035 TI - Platelet aggregation in response to ADP is highly variable in normal donors and patients on anti-platelet medication. AB - BACKGROUND: P2Y12 inhibitors are indicated in patients following percutaneous coronary intervention. Several studies have demonstrated that high on treatment platelet reactivity is correlated with outcomes yet prospective studies of guided therapy have failed to show benefit. There is a paucity of studies on the platelet aggregation response to ADP before P2Y12 therapy is started. The aim of this study was to characterize platelet responses to 20 MUM ADP by light transmission aggregometry (LTA) in a homogenous population. METHODS: Platelet aggregation was assessed in 201 patients on dual antiplatelet therapy, 98 patients on aspirin alone and 47 normal, healthy volunteers free from anti platelet medication. RESULTS: Consensus guidelines suggest that a platelet aggregation response in response to the agonist ADP of <57% is an adequate therapeutic response to P2Y12 inhibition. Seven healthy donors and 38 patients taking aspirin only had aggregation responses below 57%. CONCLUSIONS: The results of our study demonstrate that 15% of normal donors and 38% of patients taking aspirin only would be classified as having a therapeutic response to P2Y12 inhibition using current guidelines. PMID- 26562036 TI - Clinical laboratories have a critical role in test strip lot management in glucose point-of-care testing. PMID- 26562037 TI - Added value of indirect immunofluorescence intensity of automated antinuclear antibody testing in a secondary hospital setting. PMID- 26562038 TI - Impact of the routine implementation of automated indirect immunofluorescence antinuclear antibody analysis: 1 year of experience. PMID- 26562039 TI - Misidentification in laboratory medicine and diagnostic process: a neglected problem calling for action. PMID- 26562040 TI - A replacement for the testosterone "sex gap". PMID- 26562041 TI - Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice. PMID- 26562042 TI - Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice. AB - BACKGROUND: Diabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity. METHODOLOGY: The elevated sensitivity of SOCS2-/- mice to GH and possibly to PRL was the rationale to analyze the effects of multiple low dose streptozotocin (MLDSTZ)-induced diabetes in SOCS2-/- mice. RESULTS: We show that 6-month-old SOCS2-/- mice, but not 2-month-old mice, were less sensitive to MLDSTZ-induced diabetes, compared to controls. MLDSTZ treatment induced glucose intolerance in both SOCS2+/+ and SOCS2-/- mice, as shown by glucose tolerance tests, with SOCS2+/+ mice showing a more marked intolerance, compared to SOCS2-/- mice. Furthermore, insulin tolerance tests showed that the SOCS2-/- mice have an improved hypoglycemic response to exogenous insulin, compared to SOCS2+/+ mice. Moreover, in isolated islets, lipotoxic effects on insulin release could partly be overcome by ligands, which bind to GH or PRL receptors. CONCLUSION: Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of beta-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of beta-cell survival may be of relevance to islet regeneration and survival in transplantation. PMID- 26562043 TI - The association between lung cancer incidence and ambient air pollution in China: A spatiotemporal analysis. AB - BACKGROUND: China is experiencing more and more days of serious air pollution recently, and has the highest lung cancer burden in the world. OBJECTIVES: To examine the associations between lung cancer incidence and fine particles (PM2.5) and ozone in China. METHODS: We used 75 communities' data of lung cancer incidence from the National Cancer Registration of China from 1990 to 2009. The annual concentrations of fine particles (PM2.5) and ozone at 0.1 degrees *0.1 degrees spatial resolution were generated by combing remote sensing, global chemical transport models, and improvements in coverage of surface measurements. A spatial age-period-cohort model was used to examine the relative risks of lung cancer incidence associated with the air pollutants, after adjusting for impacts of age, period, and birth cohort, sex, and community type (rural and urban) as well as the spatial variation on lung cancer incidence. RESULTS: The relative risks of lung cancer incidence related to a 10 ug/m(3) increase in 2-year average PM2.5 were 1.055 (95% confidence interval (CI): 1.038, 1.072) for men, 1.149 (1.120, 1.178) for women, 1.060 (1.044, 1.075) for an urban communities, 1.037 (0.998, 1.078) for a rural population, 1.074 (1.052, 1.096) for people aged 30-65 years, and 1.111 (1.077, 1.146) for those aged over 75 years. Ozone also had a significant association with lung cancer incidence. CONCLUSIONS: The increased risks of lung cancer incidence were associated with PM2.5 and ozone air pollution. Control measures to reduce air pollution would likely lower the future incidence of lung cancer. PMID- 26562044 TI - Impact of fetal and childhood mercury exposure on immune status in children. AB - BACKGROUND: Mercury exposure have been shown to affect immune status in animals as reflected by cytokine expression. It is unclear whether low levels of exposure during fetal and/or childhood periods could impact on immune status in humans. OBJECTIVES: To test the hypothesis that fetal and childhood mercury exposure is associated with childhood cytokine profiles and to investigate whether childhood selenium levels interact with any of the associations found. METHODS: Children were recruited from a previously established birth cohort between the ages of 6-9 years for assessment and measurement of blood mercury, selenium and cytokine profile (interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13 and TNF-alpha). Multivariable linear regression models were used to assess the adjusted association of cord blood mercury concentration and current mercury concentrations with levels of the cytokine levels. We tested whether the association with current mercury level varied by current selenium level and cord blood mercury level. RESULTS: IL-10 was negatively associated with current blood mercury concentration. The effect was greatest in cases with low cord blood mercury and low current selenium concentrations. None of the other cytokine levels were associated with either cord blood or current blood mercury concentrations, except that cord blood mercury was negatively associated with IL 6. CONCLUSIONS: Childhood mercury exposure was negatively associated with childhood IL-10 levels. It is postulated that while selenium is protective, low levels of fetal mercury exposure may increase the degree of this negative association during childhood. Further studies into the clinical significance of these findings are required. PMID- 26562045 TI - The Role of Peer Support in Attaining Ideal Cardiovascular Health: Peer Pressure and Prevention. PMID- 26562046 TI - Generalizability of SPRINT Results to the U.S. Adult Population. AB - BACKGROUND: In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg. OBJECTIVES: The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized. METHODS: We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age >=50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m(2), 10 year CVD risk >=15%, or age >=75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m(2), or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with >=1 class of antihypertensive medication identified through a pill bottle review. RESULTS: Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension. CONCLUSIONS: A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT. PMID- 26562047 TI - A Comprehensive Lifestyle Peer Group-Based Intervention on Cardiovascular Risk Factors: The Randomized Controlled Fifty-Fifty Program. AB - BACKGROUND: Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global cardiovascular risk factor modification are lacking. OBJECTIVES: This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors. METHODS: A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group-based intervention group (IG) or a self management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups. RESULTS: Participants' mean age was 42 +/- 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 +/- 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component. CONCLUSIONS: The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment reported here to determine long-term sustainability of the improvements associated with peer group intervention. (Peer-Group-Based Intervention Program [Fifty-Fifty]; NCT02367963). PMID- 26562048 TI - Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice. AB - In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose dependent manner (p<0.05) after prenatal alcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (p<0.01). Furthermore, we found that mossy cells were very sensitive to alcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (p<0.05) and decreased with the growing age. Compared with WT pups, the number of apoptotic mossy cells in the hippocampus of SMS2-/- pups increased (p<0.05). Western blotting showed that the expression of activated Caspase 8 and activated Caspase 3 of hippocampal tissue in WT pups and SMS2-/- pups increases after prenatal alcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis. PMID- 26562049 TI - Differential modulation of expression of nuclear receptor mediated genes by tris(2-butoxyethyl) phosphate (TBOEP) on early life stages of zebrafish (Danio rerio). AB - As one substitute for phased-out brominated flame retardants (BFRs), tris(2 butoxyethyl) phosphate (TBOEP) is frequently detected in aquatic organisms. However, knowledge about endocrine disrupting mechanisms associated with nuclear receptors caused by TBOEP remained restricted to results from in vitro studies with mammalian cells. In the study, results of which are presented here, embryos/larvae of zebrafish (Danio rerio) were exposed to 0.02, 0.1 or 0.5MUM TBOEP to investigate expression of genes under control of several nuclear hormone receptors (estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptor alpha (TRalpha), mineralocorticoid receptor (MR), glucocorticoid receptor (GR), aryl hydrocarbon (AhR), peroxisome proliferator-activated receptor alpha (PPARalpha), and pregnane*receptor (P*R)) pathways at 120hpf. Exposure to 0.5MUM TBOEP significantly (p<0.05, one-way analysis of variance) up-regulated expression of estrogen receptors (ERs, er1, er2a, and er2b) genes and ER associated genes (vtg4, vtg5, pgr, ncor, and ncoa3), indicating TBOEP modulates the ER pathway. In contrast, expression of most genes (mr, 11betahsd, ube2i,and adrb2b) associated with the mineralocorticoid receptor (MR) pathway were significantly down-regulated. Furthermore, in vitro mammalian cell-based (MDA-kb2 and H4IIE-luc) receptor transactivation assays, were also conducted to investigate possible agonistic or antagonistic effects on AR- and AhR-mediated pathways. In mammalian cells, none of these pathways were affected by TBOEP at the concentrations studied. Receptor-mediated responses (in vivo) and mammalian cell lines receptor binding assay (in vitro) combined with published information suggest that TBOEP can modulate receptor-mediated, endocrine process (in vivo/in vitro), particularly ER and MR. PMID- 26562050 TI - Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects. AB - Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic and epoxy resins, is a ubiquitous contaminant in environment and human body. To investigate the reproductive effects of long-term exposure to low concentrations of BPA, a two-generation study was conducted using the aquatic model species of zebrafish. Our findings revealed that exposure to 1nM (0.228MUg/L) BPA for continuous two generations resulted in female-biased sex ratio in both F1 and F2 adult population, decreased sperm density, and decreased sperm quality as measured by motility, velocity, ATP content and lipid peroxidation in F1 and F2 males. Females were less sensitive to BPA exposures than males as no adverse effects were found in female gonads or gametes. Delayed hatching at 48hpf and increased malformation and mortality were found in the offspring from BPA exposed F2, but not F1 parents. Most importantly, the adverse effect on larval development and survival from BPA exposed F2 parents was paternal-specific, resulting mainly from BPA exposed males. Subsequent transcription analysis of F2 male gonads revealed dysregulated mitochondrial biogenesis and significant activation of non-canonical Wnt/planar cell polarity and Wnt/Calcium signaling pathways. Gene expression analysis of larvae from BPA exposed F2 parents showed significant reduced expression of DNA methyltransferases such as dnmt1, dnmt3, and dnmt5. In conclusion, low level BPA exposures for continuous two generations not only affects sex ratio and sperm quantity/quality in F1 and F2 adults, reproductive success in offspring from F2 parents, but also perturbs various molecular pathways potentially contributing to these BPA induced male-specific reproductive defects. PMID- 26562051 TI - An in vitro screening with emerging contaminants reveals inhibition of carboxylesterase activity in aquatic organisms. AB - Pharmaceuticals and personal care products (PPCPs) form part of the new generation of pollutants present in many freshwater and marine ecosystems. Although environmental concentrations of these bioactive substances are low, they cause sublethal effects (e.g., enzyme inhibition) in non-target organisms. However, little is known on metabolism of PPCPs by non-mammal species. Herein, an in vitro enzyme trial was performed to explore sensitivity of carboxylesterase (CE) activity of aquatic organisms to fourteen PPCPs. The esterase activity was determined in the liver of Mediterranean freshwater fish (Barbus meridionalis and Squalius laietanus), coastal marine fish (Dicentrarchus labrax and Solea solea), middle-slope fish (Trachyrhynchus scabrus), deep-sea fish (Alepocephalus rostratus and Cataetix laticeps), and in the digestive gland of a decapod crustacean (Aristeus antennatus). Results showed that 100MUM of the lipid regulators simvastatin and fenofibrate significantly inhibited (30-80% of controls) the CE activity of all target species. Among the personal care products, nonylphenol and triclosan were strong esterase inhibitors in most species (36-68% of controls). Comparison with literature data suggests that fish CE activity is as sensitive to inhibition by some PPCPs as that of mammals, although their basal activity levels are lower than in mammals. Pending further studies on the interaction between PPCPs and CE activity, we postulate that this enzyme may act as a molecular sink for certain PPCPs in a comparable way than that described for the organophosphorus pesticides. PMID- 26562052 TI - Modified intention-to-treat analysis did not bias trial results. AB - OBJECTIVE: To investigate whether analysis of the modified intention-to-treat (mITT) population with postrandomization exclusion of patients from analysis is associated with biased estimates of treatment effect compared to the conservative intention-to-treat (ITT) population. STUDY DESIGN AND SETTING: Placebo controlled, blinded randomized trials on biological or targeted interventions for rheumatoid arthritis were identified through a systematic search. Two authors independently extracted data. A random-effects meta-analysis was used to combine odds ratios as an expression of treatment effect and stratify according to the different analysis populations. RESULTS: Seventy-two randomized trials were included and analyzed (23,842 patients). Thirty trials analyzed the ITT population, 37 analyzed an mITT population, and 5 trials had an unclear analysis population. The treatment effect of active intervention compared to control, when based on mITT, was comparable to ITT (odds ratio 3.76 [95% confidence interval 3.09, 4.57], and 3.47 [2.77, 4.34]; comparison P = 0.60). CONCLUSION: We found no difference in the treatment effect between randomized trials using ITT and mITT analyses populations. This suggests that the mITT approach in rheumatoid arthritis trials investigating biological or targeted interventions does not introduce bias compared to ITT. PMID- 26562053 TI - Default network activation during episodic and semantic memory retrieval: A selective meta-analytic comparison. AB - It remains unclear whether and to what extent the default network subregions involved in episodic memory (EM) and semantic memory (SM) processes overlap or are separated from one another. This study addresses this issue through a controlled meta-analysis of functional neuroimaging studies involving healthy participants. Various EM and SM task paradigms differ widely in the extent of default network involvement. Therefore, the issue at hand cannot be properly addressed without some control for this factor. In this regard, this study employs a two-stage analysis: a preliminary meta-analysis to select EM and SM task paradigms that recruit relatively extensive default network regions and a main analysis to compare the selected task paradigms. Based on a within-EM comparison, the default network contributed more to recollection/familiarity effects than to old/new effects, and based on a within-SM comparison, it contributed more to word/pseudoword effects than to semantic/phonological effects. According to a direct comparison of recollection/familiarity and word/pseudoword effects, each involving a range of default network regions, there were more overlaps than separations in default network subregions involved in these two effects. More specifically, overlaps included the bilateral posterior cingulate/retrosplenial cortex, left inferior parietal lobule, and left anteromedial prefrontal regions, whereas separations included only the hippocampal formation and the parahippocampal cortex region, which was unique to recollection/familiarity effects. These results indicate that EM and SM retrieval processes involving strong memory signals recruit extensive and largely overlapping default network regions and differ mainly in distinct contributions of hippocampus and parahippocampal regions to EM retrieval. PMID- 26562054 TI - Event-related potentials in response to violations of content and temporal event knowledge. AB - Scripts that store knowledge of everyday events are fundamentally important for managing daily routines. Content event knowledge (i.e., knowledge about which events belong to a script) and temporal event knowledge (i.e., knowledge about the chronological order of events in a script) constitute qualitatively different forms of knowledge. However, there is limited information about each distinct process and the time course involved in accessing content and temporal event knowledge. Therefore, we analyzed event-related potentials (ERPs) in response to either correctly presented event sequences or event sequences that contained a content or temporal error. We found an N400, which was followed by a posteriorly distributed P600 in response to content errors in event sequences. By contrast, we did not find an N400 but an anteriorly distributed P600 in response to temporal errors in event sequences. Thus, the N400 seems to be elicited as a response to a general mismatch between an event and the established event model. We assume that the expectancy violation of content event knowledge, as indicated by the N400, induces the collapse of the established event model, a process indicated by the posterior P600. The expectancy violation of temporal event knowledge is assumed to induce an attempt to reorganize the event model in working memory, a process indicated by the frontal P600. PMID- 26562055 TI - Attentional focus on subjective interoceptive experience in patients with fibromyalgia. AB - OBJECTIVES: The hypervigilance model of pain perception states that patients with fibromyalgia (FM) have an enhanced sensitivity to aversive and non-aversive stimuli. Few studies have focused on enhanced interoceptive sensitivity in FM. Therefore, the aim of the present study was to investigate spontaneous sensations (SPS) in FM. DESIGN: SPS are those tingling, tickly and other kind of sensations usually perceived on the skin during periods of rest and without any external trigger. Therefore, we have investigated SPS by requiring participants to focus attention on each hand. METHODS: Eighteen patients with a diagnosis of FM and 18 matched healthy participants had to direct their gaze toward the hand tested for a period of 10s. Subsequently, they had to map and report the intensity, the number and the qualitative properties of sensations arising spontaneously. Finally, participants had to fill out questionnaires assessing cognitive and affective status that may influence the interoceptive sensations feedback. RESULTS: Patients with FM perceived SPS as significantly more intense than controls did. Additionally, SPS were perceived by the FM group as occupying an overall larger area on the hand than those reported by controls. Importantly, entering scores of pain and catastrophism as covariates produced a relative effect on the feeling of SPS. CONCLUSIONS: The outcome of this study supports the generalized hypervigilance model, suggesting that patients with FM have a perceptual style of amplification of non-aversive interoceptive stimulation, modulated by pain and catastrophizing. This is discussed in relationship to interoceptive awareness. PMID- 26562056 TI - 3D rotating wall vessel and 2D cell culture of four veterinary virus pathogens: A comparison of virus yields, portions of infectious particles and virus growth curves. AB - Only very few comparative studies have been performed that evaluate general trends of virus growth under 3D in comparison with 2D cell culture conditions. The aim of this study was to investigate differences when four animal viruses are cultured in 2D and 3D. Suid herpesvirus 1 (SuHV-1), Vesicular stomatitis virus (VSIV), Bovine adenovirus (BAdV) and Bovine parainfluenza 3 virus (BPIV-3) were cultivated in 3D rotating wall vessels (RWVs) and conventional 2D cultures. The production of virus particles, the portion of infectious particles, and the infectious growth curves were compared. For all viruses, the production of virus particles (related to cell density), including the non-infectious ones, was lower in 3D than in 2D culture. The production of only infectious particles was significantly lower in BAdV and BPIV-3 in 3D cultures in relation to cell density. The two cultivation approaches resulted in significantly different virus particle-to-TCID50 ratios in three of the four viruses: lower in SuHV-1 and BPIV 3 and higher in BAdV in 3D culture. The infectious virus growth rates were not significantly different in all viruses. Although 3D RWV culture resulted in lower production of virus particles compared to 2D systems, the portion of infectious particles was higher for some viruses. PMID- 26562057 TI - Multiple virus resistance using artificial trans-acting siRNAs. AB - Plant TAS gene encoded trans-acting siRNAs (ta-siRNAs) regulate the expression of target mRNAs by guiding their cleavage at the sequence complementary region as microRNAs. Since one TAS transcript is cleaved into multiple ta-siRNAs in a phased manner, TAS genes may be engineered to express multiple artificial ta siRNAs (ata-siRNAs) that target multiple viruses at several distinct genomic positions. To test this hypothesis, the Arabidopsis TAS3a gene was engineered to express ata-siRNAs targeting the genome of Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). Transgenic Arabidopsis thaliana plants expressing these ata-siRNAs showed high level of resistance to both viruses. These results suggest that plant TAS genes can be modified to express artificial ta-siRNAs to confer multiple virus resistance and could have broad applications for future development in virus resistance strategies. PMID- 26562058 TI - The evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matrices. AB - The collection of waterborne pathogen occurrence data often requires the concentration of microbes from large volumes of water due to the low number of microorganisms that are typically present in environmental and drinking waters. Hollow-fiber ultrafiltration (HFUF) has shown promise in the recovery of various microorganisms. This study has demonstrated that the HFUF primary concentration method is effective at recovering bacteriophage phiX174, poliovirus, enterovirus 70, echovirus 7, coxsackievirus B4 and adenovirus 41 from large volumes of tap and river water with an average recovery of all viruses of 73.4% and 81.0%, respectively. This study also evaluated an effective secondary concentration method using celite for the recovery of bacteriophage and enteric viruses tested from HFUF concentrates of both matrices. Overall, the complete concentration method (HFUF primary concentration plus celite secondary concentration) resulted in a concentration factor of 3333 and average recoveries for all viruses from tap and river waters of 60.6% and 60.0%, respectively. PMID- 26562059 TI - Load-related brain activation predicts spatial working memory performance in youth aged 9-12 and is associated with executive function at earlier ages. AB - Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. PMID- 26562060 TI - The Physiology of Cardiopulmonary Resuscitation. AB - Outcomes after cardiac arrest remain poor more than a half a century after closed chest cardiopulmonary resuscitation (CPR) was first described. This review article is focused on recent insights into the physiology of blood flow to the heart and brain during CPR. Over the past 20 years, a greater understanding of heart-brain-lung interactions has resulted in novel resuscitation methods and technologies that significantly improve outcomes from cardiac arrest. This article highlights the importance of attention to CPR quality, recent approaches to regulate intrathoracic pressure to improve cerebral and systemic perfusion, and ongoing research related to the ways to mitigate reperfusion injury during CPR. Taken together, these new approaches in adult and pediatric patients provide an innovative, physiologically based road map to increase survival and quality of life after cardiac arrest. PMID- 26562061 TI - Current cigarette smoking among adults - United States, 2005-2014. AB - Tobacco smoking is the leading cause of preventable disease and death in the United States, resulting in approximately 480,000 premature deaths and more than $300 billion in direct health care expenditures and productivity losses each year (1). To assess progress toward achieving the Healthy People 2020 objective of reducing the percentage of U.S. adults who smoke cigarettes to <=12.0%,* CDC assessed the most recent national estimates of smoking prevalence among adults aged >=18 years using data from the 2014 National Health Interview Survey (NHIS). The percentage of U.S. adults who smoke cigarettes declined from 20.9% in 2005 to 16.8% in 2014. Among daily cigarette smokers, declines were observed in the percentage who smoked 20-29 cigarettes per day (from 34.9% to 27.4%) or >=30 cigarettes per day (from 12.7% to 6.9%). In 2014, prevalence of cigarette smoking was higher among males, adults aged 25-44 years, multiracial persons and American Indian/Alaska Natives, persons who have a General Education Development certificate, live below the federal poverty level, live in the Midwest, are insured through Medicaid or are uninsured, have a disability or limitation, or are lesbian, gay, or bisexual. Proven population-based interventions, including tobacco price increases, comprehensive smoke-free laws, high impact mass media campaigns, and barrier-free access to quitting assistance, are critical to reduce cigarette smoking and smoking-related disease and death among U.S. adults. PMID- 26562064 TI - Temperature Activated Diffusion of Radicals through Ion Implanted Polymers. AB - Plasma immersion ion implantation (PIII) is a promising technique for immobilizing biomolecules on the surface of polymers. Radicals generated in a subsurface layer by PIII treatment diffuse throughout the substrate, forming covalent bonds to molecules when they reach the surface. Understanding and controlling the diffusion of radicals through this layer will enable efficient optimization of this technique. We develop a model based on site to site diffusion according to Fick's second law with temperature activation according to the Arrhenius relation. Using our model, the Arrhenius exponential prefactor (for barrierless diffusion), D0, and activation energy, EA, for a radical to diffuse from one position to another are found to be 3.11 * 10(-17) m(2) s(-1) and 0.31 eV, respectively. The model fits experimental data with a high degree of accuracy and allows for accurate prediction of radical diffusion to the surface. The model makes useful predictions for the lifetime over which the surface is sufficiently active to covalently immobilize biomolecules and it can be used to determine radical fluence during biomolecule incubation for a range of storage and incubation temperatures so facilitating selection of the most appropriate parameters. PMID- 26562062 TI - The Impact of Multipollutant Clusters on the Association Between Fine Particulate Air Pollution and Microvascular Function. AB - BACKGROUND: Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. METHODS: We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003 to 2008. RESULTS: In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction P value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% confidence interval: 4.6%, 33%) higher baseline pulse amplitude per 5 MUg/m and days with high contributions of oil and wood combustion with 16% (95% confidence interval: 0.2%, 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. CONCLUSIONS: PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil, and wood combustion was associated with higher baseline pulse amplitude but not hyperemic response. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences. PMID- 26562065 TI - New Antimicrobially Amended Media for Improved Nonpoint Source Bacterial Pollution Treatment. AB - Nonpoint source pollution (NPS) such as stormwater runoff may introduce high loads of bacteria, impairing surface water bodies. The existing filter materials in stormwater best management practices (BMP) are typically not designed to inactivate bacteria. Herein, novel filtration media were extensively tested for microbial load reduction in stormwater runoff. Red cedar wood chips (RC) were amended with different loadings of either 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride (TPA) or silver nanoparticles (AgNP). Under batch conditions at 25 degrees C, log10 removal values (LRV) up to 3.71 +/ 0.38 (mean +/- standard error) for TPA-RC and 2.25 +/- 1.00 for AgNP-RC were achieved for Escherichia coli (E. coli), whereas unmodified RC achieved less than 0.5 LRV. Similar trends were observed at 17.5 degrees C, however at low temperature (10 degrees C) no statistically significant difference in E. coli inactivation between modified and unmodified RC was detected. Inactivation kinetic studies show that TPA-RC has higher inactivation rate constants compared to AgNP-RC. Under dynamic flow conditions a mass balance approach indicates that even after remobilization up to 99.8% of E. coli removal using 9 mg/g TPA-RC compared to 64.8% for unmodified RC. This study demonstrates that RC wood chips amended with antimicrobial compounds show promising applications as filtration material for the reduction of microbiological contamination load in stormwater runoff. PMID- 26562066 TI - Stelleralides D-J and Anti-HIV Daphnane Diterpenes from Stellera chamaejasme. AB - Bioassay-guided fractionation of a petroleum ether extract of the roots of Stellera chamaejasme led to the isolation of seven new (stelleralides D-J, 1-7) and 12 known (8-19) daphnane diterpenoids. The structures and relative configurations of 1-7 were established on the basis of extensive spectroscopic analysis, including HRESIMS and comprehensive NMR techniques. All isolates were evaluated for anti-HIV activity in MT4 cells. All compounds tested, except 2, showed anti-HIV activity, and, especially, five 1alpha-alkyldaphnane diterpenoids (3, 4, 5, 10, and 11) exhibited extremely potent anti-HIV activity, with EC50 values of 0.06-1.1 nM and selectivity index values of more than 10,000. PMID- 26562067 TI - Tuning the Electronic Properties of 2-Cyano-3-phenylacrylamide Derivatives. AB - We are the first to report the synthesis of a new class of 2-cyanoarylacrylamide (2-CAA) derivatives and observe that the synthesized 2-CAA shows fluorescence properties due to the formation of a dimeric interaction of hydrogen bonds between carbonyl oxygens and amide hydrogens (C?O...H-N-C?O...H-N...); i.e., dimers are linked through dimeric N-H...O hydrogen bonds. The single-crystal X ray structure shows molecules to be hydrogen-bonded dimers, which further form a parallel stacking arrangement, mediated by significant pi-pi interactions. The (1)H NMR and fluorescence spectral studies indicate the coexistence of amide and iminol tautomers in solution, which can be influenced by the nature of the solvent. Further, the excitation-wavelength-dependent fluorescence spectrum and the biexponential fluorescence decay profiles suggest the presence of more than one emitting species; i.e., amide and iminol tautomers coexists in solution. We have also shown that the equilibrium between the two tautomers can be tuned by the judicious choice of electron-donating or -withdrawing substituents. PMID- 26562070 TI - Discovery of Nanomolar Dengue and West Nile Virus Protease Inhibitors Containing a 4-Benzyloxyphenylglycine Residue. AB - The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural peptidic building blocks synthesized via a copper-complex intermediate. A three step optimization strategy, beginning with fragment growth of the C-terminal 4 hydroxyphenylglycine to the benzyloxy ether, followed by C- and N-terminal optimization, and finally fragment merging generated compounds with in vitro affinities in the low nanomolar range. The most promising derivative reached Ki values of 12 nM at the DENV-2 and 39 nM at the WNV proteases. Several of the newly discovered protease inhibitors yielded a significant reduction of dengue and West Nile virus titers in cell-based assays of virus replication, with an EC50 value of 3.4 MUM at DENV-2 and 15.5 MUM at WNV for the most active analogue. PMID- 26562068 TI - Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils. AB - The bacterial pathogen Neisseria meningitidis expresses two major outer-membrane porins. PorA expression is subject to phase-variation (high frequency, random, on off switching), and both PorA and PorB are antigenically variable between strains. PorA expression is variable and not correlated with meningococcal colonisation or invasive disease, whereas all naturally-occurring strains express PorB suggesting strong selection for expression. We have generated N. meningitidis strains lacking expression of both major porins, demonstrating that they are dispensable for bacterial growth in vitro. The porAB mutant strain has an exponential growth rate similar to the parental strain, as do the single porA or porB mutants, but the porAB mutant strain does not reach the same cell density in stationary phase. Proteomic analysis suggests that the double mutant strain exhibits compensatory expression changes in proteins associated with cellular redox state, energy/nutrient metabolism, and membrane stability. On solid media, there is obvious growth impairment that is rescued by addition of blood or serum from mammalian species, particularly heme. These porin mutants are not impaired in their capacity to inhibit both staurosporine-induced apoptosis and a phorbol 12-myristate 13-acetate-induced oxidative burst in human neutrophils suggesting that the porins are not the only bacterial factors that can modulate these processes in host cells. PMID- 26562071 TI - One-Pot Benzo[b]phosphole Synthesis through Sequential Alkyne Arylmagnesiation, Electrophilic Trapping, and Intramolecular Phospha-Friedel-Crafts Cyclization. AB - A one-pot multicomponent synthesis of a benzo[b]phosphole derivative has been achieved by a sequence of transition-metal-catalyzed arylmagnesiation of an internal alkyne, electrophilic trapping of the resulting alkenylmagnesium species with a dichloroorganophosphine, and an intramolecular phospha-Friedel-Crafts reaction. With appropriate arylmagnesiation and P-C bond formation conditions, the present method allows for the modular and expedient preparation of benzophospholes bearing a variety of substituents on the phosphorus atom, the C2 and C3 atoms, and the "benzo" moiety. PMID- 26562069 TI - Synthetic Mimics of Bacterial Lipid A Trigger Optical Transitions in Liquid Crystal Microdroplets at Ultralow Picogram-per-Milliliter Concentrations. AB - We report synthetic six-tailed mimics of the bacterial glycolipid Lipid A that trigger changes in the internal ordering of water-dispersed liquid crystal (LC) microdroplets at ultralow (picogram-per-milliliter) concentrations. These molecules represent the first class of synthetic amphiphiles to mimic the ability of Lipid A and bacterial endotoxins to trigger optical responses in LC droplets at these ultralow concentrations. This behavior stands in contrast to all previously reported synthetic surfactants and lipids, which require near-complete monolayer coverage at the LC droplet surface to trigger ordering transitions. Surface-pressure measurements and SAXS experiments reveal these six-tailed synthetic amphiphiles to mimic key aspects of the self-assembly of Lipid A at aqueous interfaces and in solution. These and other results suggest that these amphiphiles trigger orientational transitions at ultralow concentrations through a unique mechanism that is similar to that of Lipid A and involves formation of inverted self-associated nanostructures at topological defects in the LC droplets. PMID- 26562073 TI - Comparison of sequential pancreatic duct guidewire placement technique and needle knife precut sphincterotomy for difficult biliary cannulation. AB - OBJECTIVE: Pancreatic duct guidewire placement (PDGP) includes double guidewire technique (DGT) and transpancreatic sphincterotomy (TPS). DGT can be switched to TPS with ease due to the existing guidewire in the pancreatic duct. In this study, we aimed to combine DGT and TPS as a single technique, named sequential PDGP, and to compare its performance with needle knife precut sphincterotomy (NKPS) in treating difficult biliary cannulation (BC). METHODS: A total of 83 patients with difficult BC were enrolled in this study. Of these, 63 underwent sequential PDGP and 20 underwent NKPS. Cannulation success rate, cannulation time and endoscopic retrograde cholangiopancreatography (ERCP)-related complications were prospectively recorded and compared between the two groups. RESULTS: Successful BC was achieved in 88.9% (56/63) of the patients in the sequential PDGP group compared with 70.0% (14/20) in the NKPS group (P = 0.095). Cannulation time was 7.49 +/- 5.03 min in the sequential PDGP group and 10.60 +/- 7.24 min in the NKPS group (P = 0.086). Post-ERCP pancreatitis occurred in 12.7% of patients in the sequential PDGP group and 10.0% in the NKPS group (P = 1.000). There was no significant difference in the rates of other complications (bleeding, perforation and cholangitis) between the two groups. CONCLUSIONS: Sequential PDGP is a safe and effective alternative method to NKPS in cases of difficult BC. In those with failed standard cannulation, sequential PDGP can be considered when the guidewire is inadvertently inserted into the pancreatic duct or can be placed in the pancreatic duct without difficulty. PMID- 26562072 TI - Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker. AB - BACKGROUND AND PURPOSE: Calcium-activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene-9-carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. EXPERIMENTAL APPROACH: Patch-clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. KEY RESULTS: In the presence of high intracellular Ca(2+) , A9C inhibited TMEM16A currents in a voltage-dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca(2+) concentrations, was also voltage-dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open-channel block mechanism. Activation was due to a dramatic leftward shift in the steady-state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl(-) , suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. CONCLUSIONS AND IMPLICATIONS: A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID- 26562074 TI - Effects of PEMF on patients with osteoarthritis: Results of a prospective, placebo-controlled, double-blind study. AB - This study aimed to evaluate effects of pulsed electromagnetic fields (PEMF) in a double blind study on patients with knee joint osteoarthritis. The MAGCELL ARTHRO electrode-less therapy delivered a sinusoidal magnetic field, varying in frequency between 4 and 12 Hz. In 1 cm tissue depth, magnetic flux density was 105 mT. A total of n = 57 patients were randomly assigned to the verum, PEMF or placebo group (placebo device). Their average age was 61.6 +/- 12.0 years. According to American College of Rheumatology criteria the osteoarthritis level was 2.8 +/- 0.8. Treatment was performed twice a day for 5 min over a period of 18 days. Treatment with the MAGCELL device versus control (sham exposed) showed a highly significant reduction in pain (P < 0.001), a significant reduction in stiffness (P = 0.032) and a significant reduction in disability in daily activities (P = 0.005) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scales-with a good overall treatment tolerance. In the placebo group there was no evidence of a significant change between the initial and final examination in any of the three above-mentioned WOMAC scales. Results of this partly randomized placebo-controlled double-blind study show clinically at any rate, that use of PEMF lead to highly significant better results in the treatment group compared to the placebo group with regard to the total WOMAC global score and especially for visual analogue scale. Patient assessment of the "effectiveness" was rated in 29.5% as very good and good in 27.3% compared to 0.0% and 15.4% in controls. This therapy is thus a useful complementary treatment option with no side effects. PMID- 26562075 TI - Primary myositis and abscess of iliacus muscle due to Brucella. PMID- 26562076 TI - Microsatellite evolutionary rate and pattern in Schistocerca gregaria inferred from direct observation of germline mutations. AB - Unravelling variation among taxonomic orders regarding the rate of evolution in microsatellites is crucial for evolutionary biology and population genetics research. The mean mutation rate of microsatellites tends to be lower in arthropods than in vertebrates, but data are scarce and mostly concern accumulation of mutations in model species. Based on parent-offspring segregations and a hierarchical Bayesian model, the mean rate of mutation in the orthopteran insect Schistocerca gregaria was estimated at 2.1e(-4) per generation per untranscribed dinucleotide locus. This is close to vertebrate estimates and one order of magnitude higher than estimates from species of other arthropod orders, such as Drosophila melanogaster and Daphnia pulex. We also found evidence of a directional bias towards expansions even for long alleles and exceptionally large ranges of allele sizes. Finally, at transcribed microsatellites, the mean rate of mutation was half the rate found at untranscribed loci and the mutational model deviated from that usually considered, with most mutations involving multistep changes that avoid disrupting the reading frame. Our direct estimates of mutation rate were discussed in the light of peculiar biological and genomic features of S. gregaria, including specificities in mismatch repair and the dependence of its activity to allele length. Shedding new light on the mutational dynamics of grasshopper microsatellites is of critical importance for a number of research fields. As an illustration, we showed how our findings improve microsatellite application in population genetics, by obtaining a more precise estimation of S. gregaria effective population size from a published data set based on the same microsatellites. PMID- 26562077 TI - Evaluating the extent of pharmaceuticals in surface waters of the United States using a National-scale Rivers and Streams Assessment survey. AB - To assess the potential exposure of aquatic ecosystems to active pharmaceutical ingredients, the authors conducted a national-scale, probability-based statistical survey of the occurrence of these compounds in surface waters of the United States. The survey included 182 sampling sites and targeted rivers with close proximity to urban areas. The 46 analytes reported represent many classes of active pharmaceutical ingredients (APIs), including antibiotics, diuretics, antihypertensives, anticonvulsants, and antidepressants. Of the 46 analytes, 37 were detected in at least 1 sampling location. Sulfamethoxazole (an antibiotic) was the most frequently detected compound, being measured in 141 of the 182 surface waters surveyed at concentrations ranging up to 570 ng/L. Ten of the compounds were detected in 20% or more of the sampling sites. Weighted means of the analytical measurements are used with the statistical survey design and analysis to provide national estimates of the extent of contamination for these APIs in the nation's urban rivers. Published 2015 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US Government work and as such, is in the public domain in the United States of America. PMID- 26562078 TI - Expedient Synthesis of N1-Substituted Triazole Peptidomimetics. AB - A general procedure for the rapid diversification of peptide scaffolds is described. A one-pot click reaction between a peptide-alkyne and a series of in situ generated aryl/alkyl azides affords novel N1-substituted triazole peptidomimetics. This transformation is of broad scope, operates under mild conditions, and is parallel chemical synthesis compatible. PMID- 26562079 TI - Survival analysis and microarray profiling identify Cd40 as a candidate for the Salmonella susceptibility locus, Ity5. AB - The outcome of infection with Salmonella Typhimurium in mouse models of human typhoid fever is dependent upon a coordinated complex immune response. A panel of recombinant congenic strains (RCS) derived from reciprocal backcross of A/J and C57BL/6J mice was screened for their susceptibility to Salmonella infection and two susceptibility loci, Ity4 (Immunity to Typhimurium locus 4) and Ity5, were identified. We validated Ity5 in a genetic environment free of the impact of Ity4 using a cross between A/J and 129S6. Using a time-series analysis of genome-wide transcription during infection, comparing A/J with AcB60 mice having a C57BL/6J derived Ity5 interval, we have identified the differential expression of the positional candidate gene Cd40, Cd40-associated signaling pathways, and the differential expression of numerous genes expressed in neutrophils. CD40 is known to coordinate T cell-dependent B-cell responses and myeloid cell activation. In fact, CD40 signaling is altered in A/J mice as seen by impaired IgM upregulation during infection, decreased Ig class switching, neutropenia, reduced granulocyte recruitment in response to infection and inflammation, and decreased ERK1/2 activity. These results suggest that altered CD40 signaling and granulocyte recruitment in response to infection are responsible for the Ity5-associated Salmonella susceptibility of A/J mice. PMID- 26562082 TI - [Editorial]. PMID- 26562083 TI - [Attachment Patterns and their Relation to the Development of Anxiety Symptoms in Childhood and Adolescence]. AB - From the perspective of attachment theory, insecure attachment can be seen as a key risk factor for the development of anxiety symptoms and anxiety disorders. This systematic review addresses the current state of empirical research on the relationship between attachment status and anxiety symptoms respective anxiety disorders in childhood and adolescence. 21 current international studies published between 2010 and 2014 were included in this systematic review. These studies were heterogeneous in target populations, methods and study design. The majority of studies supported the assumed correlation between insecure attachment and anxiety symptoms or anxiety disorders. These findings are more evident in studies with school-age children than with preschool children or adolescents. Furthermore, the disorganized-disoriented type of attachment seems to be a particular risk factor for the development of anxiety symptoms and anxiety disorders. Results were discussed in relation to attachment theory and with reference to the results of previous relevant reviews. PMID- 26562084 TI - [Emotion Regulation and Emotional Vulnerability in Adolescents with Anxiety Disorders]. AB - From an attachment perspective, insecure attachment patterns in both infancy and adolescence are risk factors for the development of anxiety disorders in adolescence. Dysfunctional emotion regulation and biased social information processing are possible mediating processes. This study examines differences in emotion regulation, emotional vulnerability, and behaviour inhibition in adolescents with clinical diagnosis of anxiety disorder and healthy controls. Adolescents with anxiety disorder reported more maladaptive emotion regulation depending on the specific emotion and a higher incidence of reporting hurt feelings in social interactions. In contrast, behaviour inhibition did not explain additional variance. The results suggest that adolescents with anxiety disorders show a bias in the interpretation of social interactions as frequently emotionally hurting, and the use of dysfunctional emotion regulation strategies that minimize the possibility for effective social emotion regulation by close others or therapists. The results are interpreted within attachment framework. PMID- 26562080 TI - Interactome analysis of gene expression profile reveals potential novel key transcriptional regulators of skin pathology in vitiligo. AB - Selective destruction of epidermal melanocytes is central to vitiligo (VL), a common acquired, autoimmune depigmentory disorder of the skin. Like other autoimmune diseases, the pathogenesis of VL is obscure and both multifactorial and polygenic. The prevailing theory is that VL may be part of an autoimmune diathesis. To evaluate mechanisms underlying disease development and progression, we studied genome-wide gene expression from lesional and non-lesional skin of patients with non-segmental VL. Unbiased clustering and principal components analyses reveals a 'lesional pathology'-based signature. Pathway-based analyses of the differentially expressed genes underscore processes such as melanocyte development and cell cycle as central drivers of the disease state. Interactome analysis identifies several key transcriptional regulators potentially affecting disease pathogenesis both within and 'hidden' from the data set. Finally, two genes within six identified transcriptional 'hot spots' coincide with previous VL associated genetic elements. The remaining genes in the 'hot spots' offer an additional set of potential disease-linked loci that may help to guide future studies aimed at identifying disease risk genes. PMID- 26562085 TI - [Psychodynamic-multisystemic Therapy of School Phobia due to Separation Anxiety in Day Clinic]. AB - Psychodynamic understanding and systemic approach in the multi-family treatment of a day care clinic are illustrated following the case report of a seven-year old girl with school phobia due to separation anxiety. The treatment modalities of the day clinic at the University Medical Center Muenster are described focussing on the multi-systemic approach. Using psychodynamic and systemic hypotheses the process of treatment is developed. Specific interventions, differentiated into reorganizations of inner and outer world issues, are traced to psychodynamic and systemic hypotheses. In conclusion it is argued that the integration of psychodynamic and multisystemic therapy methods in day clinic parent-child treatment provide a promising treatment approach. PMID- 26562086 TI - [Summary of the Pilot Study Short-term Psychoanalytic Child Therapy (PaCT) of Anxious Children]. AB - We provide a summary of a recently published study on Psychoanalytic Child Therapy (PaCT; Gottken, White, Klein, von Klitzing, 2014) for young children with emotional and affective symptoms. Consisting of approximately 20 psychotherapy sessions, therapists treat families in parent-child, child-alone, parent-alone settings, aiming to uncover and work through a relational theme underlying the symptoms. Thirty families were entered into a wait-list controlled study in an outpatient setting (n = 18 treatment group; n = 12 waitlist) with the aim of assessing the effectiveness of PaCT (Gottken u. von Klitzing, 2014) for 4- to 10 year-olds with anxiety disorders. After treatment, over half of the children of the treatment group no longer met criteria for anxiety disorder while no children of the control group remitted during the wait-list interval. In addition, parent, child and teacher reports showed significant symptom reduction. The pattern of results lend preliminary support to psychodynamic intervention as an effective tool for treating childhood anxiety and affective disorders and call for future randomized controlled trials to provide additional evidence for these promising effects. PMID- 26562090 TI - E-mental health preferences of Veterans with and without probable posttraumatic stress disorder. AB - Mental health care practices supported by electronic communication, referred to as e-mental health, offer ways to increase access to mental health resources. In recent years, e-mental health interventions using clinical video teleconferencing, Internet-based interventions, social networking sites, and telephones have emerged as viable, cost-effective methods to augment traditional service delivery. Whereas some research evaluates attitudes about e-mental health, few studies have assessed interest in using these approaches in a contemporary sample of U.S. Veterans. This study sought to understand willingness to use e-mental health in a diverse group of Veterans residing in Hawaii. Mailed surveys were completed by 600 Operation Iraqi Freedom/Operation Enduring Freedom Veterans and National Guard members. Results suggest that overall willingness to use e-mental health ranged from 32.2% to 56.7% depending on modality type. Importantly, Veterans who screened positive for posttraumatic stress disorder (PTSD) were significantly less likely to report willingness to use each e-mental health modality than their peers without PTSD, despite their greater desire for mental health services. These results suggest that despite solutions to logistical barriers afforded via e-mental health services, certain barriers to mental health care may persist, especially among Veterans who screen positive for PTSD. PMID- 26562091 TI - Eyes on New Product Development. PMID- 26562093 TI - Composite Resin Core Buildups With and Without Post for the Restoration of Endodontically Treated Molars Without Ferrule. AB - OBJECTIVE: The aim of this study was to investigate the restoration of highly damaged, broken-down endodontically treated molars without the ferrule effect using glass ceramic crowns on different dual-cure composite resin core buildups. METHODS AND MATERIALS: Thirty (N=30, n=15) decoronated, endodontically treated teeth (no ferrule) were restored without a ferrule with a direct buildup using the dual-curing composite Multicore HB (group MHB) or the dual-curing composite core buildup Multicore Flow in combination with glass-fiber-reinforced composite post (FRC post; group MFP). All teeth were prepared to receive bonded glass ceramic crowns (Empress CAD luted with Variolink II) and were subjected to accelerated fatigue testing. Cyclic isometric loading was applied to the palatal cusp at an angle of 30 degrees and a frequency of 5 Hz, beginning with a load of 200 N (*5000 cycles), followed by stages of 400, 600, 800, 1000, 1200, and 1400 N at a maximum of 30,000 cycles each. Specimens were loaded until failure or to a maximum of 185,000 cycles. Groups were compared using the life table survival analysis (log rank test at p=0.05). Average fracture loads and number of survived cycles were compared with one-way analysis of variance (Scheffe post hoc at p=0.05). Previously published data from the same authors about core buildups made of high-performance polymers (group HPP, n=15) and light-curing composite resin without FRC posts (group TEC, n=15) and with FRC posts (group TECP, n=15) using the same experimental setup were included for comparison. RESULTS: None of the tested specimen withstood all 185,000 load cycles. There was no significant difference in mean fracture load (p=0.376), survived cycles (p=0.422), and survival (p=0.613) between MHB (facture load 859.4 N+/-194.92) and MFP (796.13 N+/-156.34). Group HPP from a previous study appeared to have significantly higher performance than all other groups except MHB. All groups with posts were affected by an initial failure phenomenon (wide gap at the margin between the buildup/crown assembly and the root). CONCLUSIONS: HPP and MHB enhanced the performance of all-ceramic leucite-reinforced glass ceramic crowns, and insertion of a fiber-reinforced composite post was not influential when using other materials. PMID- 26562092 TI - CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock. AB - Intracellular circadian clocks, composed of clock genes that act in transcription translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein protein interactions revealed that CRY-mediated periodic binding of CK2beta to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2alpha. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY mediated BMAL1-CK2beta binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator. PMID- 26562094 TI - Tumor profiling and the incidentalome: patient decisions and risks. AB - In recent years, the field of oncology has witnessed rapid advancements in genetic sequencing simultaneously with steeply declining costs of sequencing technology. As a result, genomics-driven cancer medicine and the use of tumor profiling are quickly becoming mainstays of cancer therapy. Oncology patients can benefit from tumor profiling by allowing the selection of targeted therapies tailored to their disease. However, it is increasingly recognized that the process of determining a tumor DNA sequence may lead to incidental discovery of underlying germline mutations which can impact other aspects of a patient's health, and that of their family. How to handle the 'incidentalome' has been the subject of recent public debate, yet patient education about the potential risks of tumor profiling remains sparse. Patient perspectives and clinical implications of the tumor incidentalome must be specifically addressed by the oncology community as tumor profiling expands to become a new standard of care. PMID- 26562096 TI - Dose reduction with iterative reconstruction for coronary CT angiography: a systematic review and meta-analysis. AB - OBJECTIVE: To investigate the achievable radiation dose reduction for coronary CT angiography (CCTA) with iterative reconstruction (IR) in adults and the effects on image quality. METHODS: PubMed and EMBASE were searched, and original articles concerning IR for CCTA in adults using prospective electrocardiogram triggering were included. Primary outcome was the effective dose using filtered back projection (FBP) and IR. Secondary outcome was the effect of IR on objective and subjective image quality. RESULTS: The search yielded 1616 unique articles, of which 10 studies (1042 patients) were included. The pooled routine effective dose with FBP was 4.2 mSv [95% confidence interval (CI) 3.5-5.0]. A dose reduction of 48% to a pooled effective dose of 2.2 mSv (95% CI 1.3-3.1) using IR was reported. Noise, contrast-to-noise ratio and subjective image quality were equal or improved in all but one study, whereas signal-to-noise ratio was decreased in two studies with IR at reduced dose. CONCLUSION: IR allows for CCTA acquisition with an effective dose of 2.2 mSv with preserved objective and subjective image quality. PMID- 26562095 TI - Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis. AB - OBJECTIVE: Contrast media (CM) are a major cause of nephropathy in high-risk patients. The aim of this study was to examine the effects of carnitine (CAR) in advanced nephrotoxicity due to CM administration in rats with glycerol-induced renal functional disorder. METHODS: 40 rats were divided randomly into five groups (n = 8): (1) healthy group; (2) glycerol only (GLY); (3) glycerol and CM (GLY + CM); (4) glycerol, CM and 200 mg kg(-1) carnitine (CAR200, Carnitene((r)); Sigma-tau/Santa Farma, Istanbul, Turkey); and (5) glycerol, CM and 400 mg kg(-1) carnitine (CAR400). Kidney injury was induced with a single-dose, intramuscular injection of 10 ml kg(-1) body weight (b.w.) of GLY. CAR was administered intraperitoneally. CM (8 ml kg(-1) b.w. iohexol, OmnipaqueTM; Opakim Medical Products, Istanbul, Turkey) was infused via the tail vein to the rats in Groups 3 5. RESULTS: l-carnitine administration significantly decreased serum creatinine and blood urea nitrogen levels. Superoxide dismutase and glutathione activity increased significantly in the treatment groups compared with the nephrotoxic groups. CAR400 significantly reduced malondialdehyde levels to healthy levels. In the treatment groups, tumour necrosis factor (TNF)-alpha, transforming growth factor 1beta, interleukin 1beta and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-alpha and nuclear factor kappa-beta (NF-kappaB) protein expression increased after CM and CAR administration reduced both TNF alpha and NF-kappaB expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups. CONCLUSION: The results reveal that l-carnitine protects the oxidant/antioxidant balance and decreases proinflammatory cytokines and apoptosis in CM-induced nephrotoxicity in rats with underlying pathology. ADVANCES IN KNOWLEDGE: Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN. PMID- 26562097 TI - Ultrasound-guided procedures to treat sport-related muscle injuries. AB - Ultrasound is well known as a low-cost, radiation-free and effective imaging technique to guide percutaneous procedures. The lower limb muscles represent a good target to perform such procedures under ultrasound guidance, thus allowing for clear and precise visualization of the needle during the whole procedure. The knowledge of guidelines and technical aspects is mandatory to act in the most safe and accurate way on target tissues that can be as small as a few millimetres. This review will focus above the local treatments of traumatic lower limb muscle injuries described in literature, focusing on new and promising approaches, such as platelet-rich plasma treatment of muscle tears in athletes. For each procedure, a brief how-to-do practical guide will be provided, emphasizing precautions and tricks based on day-by-day experience that may help to improve the outcome of percutaneous ultrasound-guided procedures around the lower limb muscles. PMID- 26562099 TI - Post-mortem CT and MRI: appropriate post-mortem imaging appearances and changes related to cardiopulmonary resuscitation. AB - Post-mortem cross-sectional imaging in the form of CT and, less frequently, MRI is an emerging facility in the evaluation of cause-of-death and human identification for the coronial service as well as in assisting the forensic investigation of suspicious deaths and homicide. There are marked differences between the radiological evaluation and interpretation of the CT and MRI features of the live patient (i.e. antemortem imaging) and the evaluation and interpretation of post-mortem CT and MRI appearances. In addition to the absence of frequently utilized tissue enhancement following intravenous contrast administration in antemortem imaging, there are a number of variable changes which occur in the tissues and organs of the body as a normal process following death, some of which are, in addition, affected significantly by environmental factors. Many patients and victims will also have undergone aggressive attempts at cardiopulmonary resuscitation in the perimortem period which will also significantly alter post-mortem CT and MRI appearances. It is paramount that the radiologist and pathologist engaged in the interpretation of such post-mortem imaging are familiar with the appropriate non-pathological imaging changes germane to death, the post-mortem interval and cardiopulmonary resuscitation in order to avoid erroneously attributing such changes to trauma or pathology. Some of the more frequently encountered radiological imaging considerations of this nature will be reviewed. PMID- 26562098 TI - Pulmonary ground-glass nodules diagnosis: mean change rate of peak CT number as a discriminative factor of pathology during a follow-up. AB - OBJECTIVE: We aimed to analyse the peak CT number (PEAK) in CT number histogram of ground-glass nodules (GGN), meaning the most frequent density of pixels in the image of pulmonary nodule, based on three-dimensional (3D) reconstructive model pre-operatively, and the mean rate of PEAK change (V-PEAK) during a follow-up of GGN for differential diagnosis between pre-invasive adenocarcinoma (PIA) and invasive adenocarcinoma (IAC). METHODS: CT number histogram of pixels in GGN was made automatically by 3D measurement software. Diameter, total volume, PEAK and V PEAK were measured from CT data sets of different groups classified by pathology, subtype and number of GGN, respectively. RESULTS: Among all 102 cases, 47 were PIA, including atypical adenomatous hyperplasia (n = 29) and adenocarcinoma in situ (n = 18), and 55 were IAC, including minimally IAC (MIA, n = 4). By Wilcoxon test, PEAK of IAC was significantly higher than that of PIA (p < 0.001). By receiver operating curve analysis, area under the curve (AUC) was 0.857 and threshold -820.50 Hounsfield units (HU) for differentiation between PIA and IAC. V-PEAK of IAC was unexpectedly remarkably smaller than that of PIA (p < 0.001) with AUC and threshold being 0.810 and -0.829 HU day(-1), respectively. CONCLUSION: Pre-operative PEAK and V-PEAK, which interpret and evaluate the change of volume and density of pulmonary nodule simultaneously from both exterior and interior perspectives, can help to distinguish IAC from PIA. ADVANCES IN KNOWLEDGE: This study provided researchers of GGN another perspective, taking both volume and density of nodules into consideration for pathological evaluation. PMID- 26562100 TI - Effects of Placental Ischemia Are Attenuated by 1,25-Dihydroxyvitamin D Treatment and Associated with Reduced Apoptosis and Increased Autophagy. AB - We evaluated the effects of administration of 1,25-dihydroxyvitamin D (1,25(OH)2D) during pregnancy on relieving adverse outcomes of preeclampsia and the pathologic and biochemical changes in reduction in uteroplacental perfusion (RUPP) model of rats. On day 1, 7, and 14 of pregnancy, rats in pregnant RUPP plus 1,25(OH)2D (RUPP+VD) group (n = 15) received 120 ng/100 g body weight/week of 1,25(OH)2D by subcutaneous injection, while rats in normal pregnant (n = 12) and the RUPP group (n = 14) received 1,25(OH)2D vehicle (saline solution). On day 19 of pregnancy, after measure of blood pressure and cardiac function and urine collection, rats were euthanized, and fetal and maternal serum, placenta, and heart and kidney were collected. Fetal mortality, urinary protein, glucose, and parameters for kidney function in serum were measured. We evaluated vitamin D receptor expression and pathological and ultrastructural changes in rat heart, kidney, and placenta. Levels of oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and autophagy were measured in placenta. Compared to RUPP rats, 1,25(OH)2D decreased fetal mortality, mean blood pressure, 24-h urinary protein, urine microalbumin, and hyperglycemia in RUPP+VD rats. These were consistent with the improvements of structure impairment in heart, kidney, and placenta of RUPP rat by 1,25(OH)2D. In placenta of RUPP rat, the decrease in oxidative stress and ER stress by 1,25(OH)2D treatment was accompanied by autophagy activation and apoptosis attenuation. 1,25(OH)2D plays a beneficial effect on preeclampsia at the early gestation and might be used as a potential protective agent for preeclampsia. However, the RUPP model only recapitulated the hypoxic origin of preeclampsia; further randomized controlled trial is expected to be performed for validation and evaluation. PMID- 26562101 TI - Risk Factors for and Behavioral Consequences of Direct Versus Indirect Exposure to Violence. AB - Research suggests that direct exposure (personal victimization) and indirect exposure (witnessing or hearing about the victimization of a family member, friend, or neighbor) to violence are correlated. However, questions remain about the co-occurrence of these phenomena within individuals. We used data on 1915 youths (with an average age of 12 years at baseline) from the Project on Human Development in Chicago Neighborhoods to examine this issue. Results indicated that youths who tended to be personally victimized were also likely to witness violence; conversely, youths who disproportionately witnessed violence were relatively unlikely to experience personal victimization. In addition, direct and indirect exposures to violence were associated with subsequent adverse outcomes in similar ways. The key distinguishing factor was, rather, the cumulative level of violence (both direct and indirect) to which youths were exposed. PMID- 26562102 TI - Barriers to Cervical Screening Among Sex Workers in Vancouver. AB - OBJECTIVES: We longitudinally examined the social, structural, and geographic correlates of cervical screening among sex workers in Metropolitan Vancouver, British Columbia, to determine the roles that physical and social geography play in routine reproductive health care access. METHODS: Analysis drew on (2010-2013) data from an open prospective cohort of sex workers (An Evaluation of Sex Workers' Health Access). We used multivariable logistic regression with generalized estimating equations (GEE) to model correlates of regular cervical screening. RESULTS: At baseline, 236 (38.6%) of 611 sex workers in our sample had received cervical screening, and 63 (10.3%) were HIV-seropositive. In multivariable GEE analysis, HIV-seropositivity (adjusted odds ratio [AOR] = 1.65; 95% confidence interval [CI] = 1.06, 2.58) and accessing outreach services (AOR = 1.35; 95% CI = 1.09, 1.66) were correlated with regular cervical screening. Experiencing barriers to health care access (e.g., poor treatment by health care staff, limited hours of operation, and language barriers) reduced odds of regular Papanicolaou testing (AOR = 0.81; 95% CI = 0.65, 1.00). CONCLUSIONS: Sex workers in Metropolitan Vancouver had suboptimal levels of cervical screening. Innovative mobile outreach service delivery models offering cervical screening as one component of sex worker-targeted comprehensive sexual and reproductive health services may hold promise. PMID- 26562103 TI - Legal Barriers to Adolescent Participation in Research About HIV and Other Sexually Transmitted Infections. AB - Whether adolescents can participate in clinical trials of pharmacologic therapies for HIV prevention, such as preexposure prophylaxis, without parental permission hinges on state minor consent laws. Very few of these laws explicitly authorize adolescents to consent to preventive services for HIV and other sexually transmitted infections. Unclear state laws may lead to research cessation. We have summarized legal, ethical, and policy considerations related to adolescents' participation in HIV and sexually transmitted infection prevention research in the United States, and we have explored strategies for facilitating adolescents' access. PMID- 26562104 TI - Nongovernment Philanthropic Spending on Public Health in the United States. AB - The objective of this study was to estimate the dollar amount of nongovernment philanthropic spending on public health activities in the United States. Health expenditure data were derived from the US National Health Expenditures Accounts and the US Census Bureau. Results reveal that spending on public health is not disaggregated from health spending in general. The level of philanthropic spending is estimated as, on average, 7% of overall health spending, or about $150 billion annually according to National Health Expenditures Accounts data tables. When a point estimate of charity care provided by hospitals and office based physicians is added, the value of nongovernment philanthropic expenditures reaches approximately $203 billion, or about 10% of all health spending annually. PMID- 26562105 TI - Halfdan Mahler: Architect and Defender of the World Health Organization "Health for All by 2000" Declaration of 1978. PMID- 26562106 TI - Toxicity of Botanical Medicines: An Overlooked Global Health Problem. PMID- 26562107 TI - Improving Adolescent Parenting: Results From a Randomized Controlled Trial of a Home Visiting Program for Young Families. AB - OBJECTIVES: Our aim was to estimate the effects of Healthy Families Massachusetts, a statewide home visiting program serving first-time adolescent parents, on parenting, child development, educational attainment, family planning, and maternal health and well-being. METHODS: We used a randomized controlled trial design to randomly assign the 704 participants to a group receiving home visiting services or a control group. Between 2008 and 2012, telephone and in-person interviews were conducted and administrative data obtained at 12 and 24 months after enrollment. Intention-to-treat analyses compared group differences across 5 outcome domains: parenting, child health and development, educational and economic achievement, family planning, and parental health and well-being. RESULTS: The home visiting program had a positive influence on parenting stress, college attendance, condom use, intimate partner violence, and engagement in risky behaviors. No negative findings were observed. CONCLUSIONS: A paraprofessional home visiting program specifically targeting young mothers appears effective in domains of particular salience to young parents and their infants and toddlers. Expanding participation in the program appears a worthy goal for program administrators and policymakers. PMID- 26562108 TI - Communities of Color Creating Healthy Environments to Combat Childhood Obesity. AB - Ethnic and racial health disparities present an enduring challenge to community based health promotion, which rarely targets their underlying population-level determinants (e.g., poverty, food insecurity, health care inequity). We present a novel 3-lens prescription for using community organizing to treat these determinants in communities of color based on the Robert Wood Johnson Foundation's Communities Creating Healthy Environments initiative, the first national project to combat childhood obesity in communities of color using community organizing strategies. The lenses--Social Justice, Culture-Place, and Organizational Capacity-Organizing Approach--assist health professional-community partnerships in planning and evaluating community organizing-based health promotion programs. These programs activate community stakeholders to alter their community's disease-causing, population-level determinants through grassroots policy advocacy, potentially reducing health disparities affecting communities of color. PMID- 26562109 TI - Community-Based Health Financing and Child Stunting in Rural Rwanda. AB - OBJECTIVES: We analyzed the likelihood of rural children (aged 6-24 months) being stunted according to whether they were enrolled in Mutuelles, a community-based health-financing program providing health insurance to rural populations and granting them access to health care, including nutrition services. METHODS: We retrieved health facility data from the District Health System Strengthening Tool and calculated the percentage of rural health centers that provided nutrition related services required by Mutuelles' minimum service package. We used data from the 2010 Rwanda Demographic and Health Survey and performed multilevel logistic analysis to control for clustering effects and sociodemographic characteristics. The final sample was 1061 children. RESULTS: Among 384 rural health centers, more than 90% conducted nutrition-related campaigns and malnutrition screening for children. Regardless of poverty status, the risk of being stunted was significantly lower (odds ratio = 0.60; 95% credible interval = 0.41, 0.83) for Mutuelles enrollees. This finding was robust to various model specifications (adjusted for Mutuelles enrollment, poverty status, other variables) or estimation methods (fixed and random effects). CONCLUSIONS: This study provides evidence of the effectiveness of Mutuelles in improving child nutrition status and supported the hypothesis about the role of Mutuelles in expanding medical and nutritional care coverage for children. PMID- 26562110 TI - Public Health and Hospitals: Lessons Learned From Partnerships in a Changing Health Care Environment. AB - Recent changes in policymaking, such as the passage of the Patient Protection and Affordable Care Act, have ushered in a new era in community health partnerships. To investigate characteristics of effective collaboration between hospitals, their parent systems, and the public health community, with the support of major hospital, medical, and public health associations, we compiled a list of 157 successful partnerships. This set was subsequently narrowed to 12 successful and diverse partnerships. After conducting site visits in each of the partnerships' communities and interviews with key partnership participants, we extracted lessons about their success. The lessons we have learned from our investigation have the potential to assist others as they develop partnerships. PMID- 26562111 TI - Increasing the Incidence and Influence of Systematic Reviews on Health Policy and Practice. PMID- 26562112 TI - A Public Health of Consequence. PMID- 26562113 TI - Patterns and Trends of Newly Diagnosed HIV Infections Among Adults and Adolescents in Correctional and Noncorrectional Facilities, United States, 2008 2011. AB - OBJECTIVES: We aimed to determine whether the patterns and trends of HIV infections newly diagnosed within correctional and noncorrectional facilities differ. METHODS: We classified persons newly diagnosed with HIV infection in the United States between 2008 and 2011 (n = 181,710) by correctional and noncorrectional facilities where diagnoses were first made, and stratified by sex, age group, race/ethnicity, transmission category, and diagnosis year. RESULTS: An estimated 9187 persons were newly diagnosed with HIV infection in 2008 to 2011 while incarcerated, representing approximately 5.1% of the 181,710 HIV infections diagnosed in the United States during this period. Of these incarcerated persons, 84% were male, 30% were aged 30 to 39 years, 59% were Black/African American, and 51% of the men had been exposed through male-to-male sexual contact. Yearly numbers of diagnoses declined by 9.9% in correctional versus 0.3% in noncorrectional facilities. The percentage with a late HIV diagnosis was significantly lower in correctional than in noncorrectional facilities (prevalence ratio = 0.52; 95% confidence interval = 0.49, 0.55). CONCLUSIONS: Initial HIV diagnosis occurred sooner after HIV infection onset in correctional than in noncorrectional settings, pointing to the need for efficient referral systems after release. PMID- 26562114 TI - Sociodemographic Predictors of Vaccination Exemptions on the Basis of Personal Belief in California. AB - OBJECTIVES: We examined the variability in the percentage of students with personal belief exemptions (PBEs) from mandatory vaccinations in California schools and communities according to income, education, race, and school characteristics. METHODS: We used spatial lag models to analyze 2007-2013 PBE data from the California Department of Public Health. The analyses included school- and regional-level models, and separately examined the percentage of students with exemptions in 2013 and the change in percentages over time. RESULTS: The percentage of students with PBEs doubled from 2007 to 2013, from 1.54% to 3.06%. Across all models, higher median household income and higher percentage of White race in the population, but not educational attainment, significantly predicted higher percentages of students with PBEs in 2013. Higher income, White population, and private school type significantly predicted greater increases in exemptions from 2007 to 2013, whereas higher educational attainment was associated with smaller increases. CONCLUSIONS: Personal belief exemptions are more common in areas with a higher percentage of White race and higher income. PMID- 26562115 TI - Public Health's Falling Share of US Health Spending. AB - We examined trends in US public health expenditures by analyzing historical and projected National Health Expenditure Accounts data. Per-capita public health spending (inflation-adjusted) rose from $39 in 1960 to $281 in 2008, and has fallen by 9.3% since then. Public health's share of total health expenditures rose from 1.36% in 1960 to 3.18% in 2002, then fell to 2.65% in 2014; it is projected to fall to 2.40% in 2023. Public health spending has declined, potentially undermining prevention and weakening responses to health inequalities and new health threats. PMID- 26562116 TI - Realizing Reproductive Health Equity Needs More Than Long-Acting Reversible Contraception (LARC). PMID- 26562117 TI - The Public Health Framework of Legalized Marijuana in Colorado. AB - On January 1, 2014, Colorado became the first state in the nation to sell legal recreational marijuana for adult use. As a result, Colorado has had to carefully examine potential population health and safety impacts as well as the role of public health in response to legalization. We have discussed an emerging public health framework for legalized recreational marijuana. We have outlined this framework according to the core public health functions of assessment, policy development, and assurance. In addition, we have discussed challenges to implementing this framework that other states considering legalization may face. PMID- 26562118 TI - Free Bus Travel and Physical Activity, Gait Speed, and Adiposity in the English Longitudinal Study of Ageing. AB - OBJECTIVES: We investigated associations between having a bus pass, enabling free local bus travel across the United Kingdom for state pension-aged people, and physical activity, gait speed, and adiposity. METHODS: We used data on 4650 bus pass-eligible people (aged >= 62 years) at wave 6 (2012-2013) of the English Longitudinal Study of Ageing in regression analyses. RESULTS: Bus pass holders were more likely to be female (odds ratio [OR] = 1.67; 95% confidence interval [CI] = 1.38, 2.02; P < .001), retired (OR = 2.65; 95% CI = 2.10, 3.35; P < .001), without access to a car (OR = 2.78; 95% CI = 1.83, 4.21; P < .001), to use public transportation (OR = 10.26; 95% CI = 8.33, 12.64; P < .001), and to be physically active (OR = 1.43; 95% CI = 1.12, 1.84; P = .004). Female pass holders had faster gait speed (b = 0.06 meters per second; 95% CI = 0.02, 0.09; P = .001), a body mass index 1 kilogram per meter squared lower (b = -1.20; 95% CI = -1.93, -0.46; P = .001), and waist circumference 3 centimeters smaller (b = -3.32; 95% CI = 5.02, -1.62; P < .001) than women without a pass. CONCLUSIONS: Free bus travel for older people helps make transportation universally accessible, including for those at risk for social isolation. Those with a bus pass are more physically active. Among women in particular, the bus pass is associated with healthier aging. PMID- 26562119 TI - Access to Care and Chronic Disease Outcomes Among Medicaid-Insured Persons Versus the Uninsured. AB - OBJECTIVES: We sought to determine the association between Medicaid coverage and the receipt of appropriate clinical care. METHODS: Using the 1999 to 2012 National Health and Nutritional Examination Surveys, we identified adults aged 18 to 64 years with incomes below the federal poverty level, and compared outpatient visit frequency, awareness, and control of chronic diseases between the uninsured (n = 2975) and those who had Medicaid (n = 1485). RESULTS: Respondents with Medicaid were more likely than the uninsured to have at least 1 outpatient physician visit annually, after we controlled for patient characteristics (odds ratio [OR] = 5.0; 95% confidence interval [CI] = 3.8, 6.6). Among poor persons with evidence of hypertension, Medicaid coverage was associated with greater awareness (OR = 1.83; 95% CI = 1.26, 2.66) and control (OR = 1.69; 95% CI = 1.32, 2.27) of their condition. Medicaid coverage was also associated with awareness of being overweight (OR = 1.30; 95% CI = 1.02, 1.67), but not with awareness or control of diabetes or hypercholesterolemia. CONCLUSIONS: Among poor adults nationally, Medicaid coverage appears to facilitate outpatient physician care and to improve blood pressure control. PMID- 26562120 TI - Inequalities of Income and Inequalities of Longevity: A Cross-Country Study. AB - OBJECTIVES: We examined the effects of market income inequality (income inequality before taxes and transfers) and income redistribution via taxes and transfers on inequality in longevity. METHODS: We used life tables to compute Gini coefficients of longevity inequality for all individuals and for individuals who survived to at least 10 years of age. We regressed longevity inequality on market income inequality and income redistribution, and we controlled for potential confounders, in a cross-sectional time-series sample of up to 28 predominantly Western developed countries and up to 37 years (1974-2011). RESULTS: Income inequality before taxes and transfers was positively associated with inequality in the number of years lived; income redistribution (the difference between market income inequality and income inequality after taxes and transfers were accounted for) was negatively associated with longevity inequality. CONCLUSIONS: To the extent that our estimated effects derived from observational data are causal, governments can reduce longevity inequality not only via public health policies, but also via their influence on market income inequality and the redistribution of incomes from the relatively rich to the relatively poor. PMID- 26562121 TI - Chinese Immigrant Religious Institutions' Variability in Views on Preventing Sexual Transmission of HIV. AB - OBJECTIVES: We examined Chinese immigrant religious institutions' views on teaching about preventing sexual transmission of HIV and the consistency of their views with public health best practices in HIV prevention. METHODS: We used 2009 to 2011 survey data from 712 members of 20 New York City-based Chinese immigrant religious institutions to analyze their views on (1) teaching adolescents about condoms, (2) discussing homosexuality nonjudgmentally, and (3) promoting abstinence until marriage. RESULTS: Religion type was a significant predictor of views in the 3 domains, with Evangelical Protestants in least agreement with public health best practices, Buddhists in most agreement, and mainline Protestants between them. Greater HIV knowledge was significantly associated with agreement with best practices in all 3 domains. The frequency of prayer, meditation, or chanting and the level of acculturation were significant predictors of views on teaching adolescents about condoms and promoting abstinence until marriage. CONCLUSIONS: The best practice messages about HIV prevention that Chinese immigrant religious institutions find acceptable vary according to religion type and several other key factors, including HIV knowledge; frequency of prayer, meditation, or chanting; and level of acculturation. PMID- 26562122 TI - Evaluating Public Health Interventions: 1. Examples, Definitions, and a Personal Note. AB - In the first contribution to a new section in AJPH that will address critical methodological issues in evaluations of public health interventions, I will discuss topics in study design and analysis, covering the most innovative emerging methodologies and providing an overview of best practices. The methods considered are motivated by public health evaluations, both domestic and global. In this first contribution, I also define implementation science, program evaluation, impact evaluation, and cost-effectiveness research, disciplines that have tremendous methodological and substantive overlap with evaluation of public health interventions--the focus of this section. PMID- 26562124 TI - Substance Use and Cumulative Exposure to American Society: Findings From Both Sides of the US-Mexico Border Region. AB - OBJECTIVES: We investigated whether Mexican immigration to the United States exerts transnational effects on substance use in Mexico and the United States. METHODS: We performed a cross-sectional survey of 2336 Mexican Americans and 2460 Mexicans in 3 Texas border metropolitan areas and their sister cities in Mexico (the US-Mexico Study on Alcohol and Related Conditions, 2011-2013). We collected prevalence and risk factors for alcohol and drug use; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, alcohol-use disorders; and 2 symptoms (hazardous use and quit or control) of drug use disorder across a continuum of migration experiences in the Mexican and Mexican American populations. RESULTS: Compared with Mexicans with no migrant experience, the adjusted odds ratios for this continuum of migration experiences ranged from 1.10 to 8.85 for 12-month drug use, 1.09 to 5.07 for 12-month alcohol use disorder, and 1.13 to 9.95 for 12 month drug-use disorder. Odds ratios increased with longer exposure to US society. These findings are consistent with those of 3 previous studies. CONCLUSIONS: People of Mexican origin have increased prevalence of substance use and disorders with cumulative exposure to US society. PMID- 26562123 TI - Housing Status, Medical Care, and Health Outcomes Among People Living With HIV/AIDS: A Systematic Review. AB - BACKGROUND: Accumulating evidence suggests responses to HIV that combine individual-level interventions with those that address structural or contextual factors that influence risks and health outcomes of infection. Housing is such a factor. Housing occupies a strategic position as an intermediate structural factor, linking "upstream" economic, social, and cultural determinants to the more immediate physical and social environments in which everyday life is lived. The importance of housing status for HIV prevention and care has been recognized, but much of this attention has focused on homeless individuals as a special risk group. Analyses have less often addressed community housing availability and conditions as factors influencing population health or unstable, inadequate, or unaffordable housing as a situation or temporary state. A focus on individual level characteristics associated with literal homelessness glosses over social, economic, and policy drivers operating largely outside any specific individual's control that affect housing and residential environments and the health resources or risk exposures such contexts provide. OBJECTIVES: We examined the available empirical evidence on the association between housing status (broadly defined), medical care, and health outcomes among people with HIV and analyzed results to inform future research, program development, and policy implementation. SEARCH METHODS: We searched 8 electronic health and social science databases from January 1, 1996, through March 31, 2014, using search terms related to housing, dwelling, and living arrangements and HIV and AIDS. We contacted experts for additional literature. SELECTION CRITERIA: We selected articles if they were quantitative analyses published in English, French, or Spanish that included at least 1 measure of housing status as an independent variable and at least 1 health status, health care, treatment adherence, or risk behavior outcome among people with HIV in high-income countries. We defined housing status to include consideration of material or social dimensions of housing adequacy, stability, and security of tenure. DATA COLLECTION AND ANALYSIS: Two independent reviewers performed data extraction and quality appraisal. We used the Cochrane Risk of Bias Tool for randomized controlled trials and a modified version of the Newcastle Ottawa Quality Appraisal Tool for nonintervention studies. In our quality appraisal, we focused on issues of quality for observational studies: appropriate methods for determining exposure and measuring outcomes and methods to control confounding. RESULTS: Searches yielded 5528 references from which we included 152 studies, representing 139,757 HIV-positive participants. Most studies were conducted in the United States and Canada. Studies examined access and utilization of HIV medical care, adherence to antiretroviral medications, HIV clinical outcomes, other health outcomes, emergency department and inpatient utilization, and sex and drug risk behaviors. With rare exceptions, across studies in all domains, worse housing status was independently associated with worse outcomes, controlling for a range of individual patient and care system characteristics. CONCLUSIONS: Lack of stable, secure, adequate housing is a significant barrier to consistent and appropriate HIV medical care, access and adherence to antiretroviral medications, sustained viral suppression, and risk of forward transmission. Studies that examined the history of homelessness or problematic housing years before outcome assessment were least likely to find negative outcomes, homelessness being a potentially modifiable contextual factor. Randomized controlled trials and observational studies indicate an independent effect of housing assistance on improved outcomes for formerly homeless or inadequately housed people with HIV. Housing challenges result from complex interactions between individual vulnerabilities and broader economic, political, and legal structural determinants of health. The broad structural processes sustaining social exclusion and inequality seem beyond the immediate reach of HIV interventions, but changing housing and residential environments is both possible and promising. PMID- 26562125 TI - Accelerated Adoption of Smoke-Free Laws After Ratification of the World Health Organization Framework Convention on Tobacco Control. AB - OBJECTIVES: We sought to evaluate the effect of ratifying the World Health Organization Framework Convention on Tobacco Control (FCTC) on countries enacting smoke-free laws covering indoor workplaces, restaurants, and bars. METHODS: We compared adoption of smoke-free indoor workplace, restaurant, and bar laws in countries that did versus did not ratify the FCTC, accounting for years since the ratification of the FCTC and for countries' World Bank income group. RESULTS: Ratification of the FCTC significantly (P < .001) increased the probability of smoke-free laws. This effect faded with time, with a half-life of 3.1 years for indoor workplaces and 3.8 years for restaurants and bars. Compared with high income countries, upper-middle-income countries had a significantly higher probability of smoke-free indoor workplace laws. CONCLUSIONS: The FCTC accelerated the adoption of smoke-free indoor workplace, restaurant, and bar laws, with the greatest effect in the years immediately following ratification. The policy implication is that health advocates must increase efforts to secure implementation of FCTC smoke-free provisions in countries that have not done so. PMID- 26562126 TI - Health Profiles of Newly Arrived Refugee Children in the United States, 2006 2012. AB - OBJECTIVES: We conducted a large-scale study of newly arrived refugee children in the United States with data from 2006 to 2012 domestic medical examinations in 4 sites: Colorado; Minnesota; Philadelphia, Pennsylvania; and Washington State. METHODS: Blood lead level, anemia, hepatitis B virus (HBV) infection, tuberculosis infection or disease, and Strongyloides seropositivity data were available for 8148 refugee children (aged < 19 years) from Bhutan, Burma, Democratic Republic of Congo, Ethiopia, Iraq, and Somalia. RESULTS: We identified distinct health profiles for each country of origin, as well as for Burmese children who arrived in the United States from Thailand compared with Burmese children who arrived from Malaysia. Hepatitis B was more prevalent among male children than female children and among children aged 5 years and older. The odds of HBV, tuberculosis, and Strongyloides decreased over the study period. CONCLUSIONS: Medical screening remains an important part of health care for newly arrived refugee children in the United States, and disease risk varies by population. PMID- 26562129 TI - Cascade of Care for Hepatitis C Virus Infection Within the US Veterans Health Administration. AB - OBJECTIVES: We measured the quality of HCV care using a cascade of HCV care model. METHODS: We estimated the number of patients diagnosed with chronic HCV, linked to HCV care, treated with HCV antivirals, and having achieved a sustained virologic response (SVR) in the electronic medical record data from the Veterans Health Administration's Corporate Data Warehouse and the HCV Clinical Case Registry in 2013. RESULTS: Of the estimated 233,898 patients with chronic HCV, 77% (181,168) were diagnosed, 69% (160,794) were linked to HCV care, 17% (39,388) were treated with HCV antivirals, and 7% (15,983) had achieved SVR. CONCLUSIONS: This Cascade of HCV Care provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems. PMID- 26562128 TI - Differential Child Maltreatment Risk Across Deployment Periods of US Army Soldiers. AB - OBJECTIVES: We described the risk for maltreatment among toddlers of US Army soldiers over different deployment cycles to develop a systematic response within the US Army to provide families appropriate supports. METHODS: We conducted a person-time analysis of substantiated maltreatment reports and medical diagnoses among children of 112,325 deployed US Army soldiers between 2001 and 2007. RESULTS: Risk of maltreatment was elevated after deployment for children of soldiers deployed once but not for children of soldiers deployed twice. During the 6 months after deployment, children of soldiers deployed once had 4.43 substantiated maltreatment reports and 4.96 medical diagnoses per 10,000 child months. The highest maltreatment rate among children of soldiers deployed twice occurred during the second deployment for substantiated maltreatment (4.83 episodes per 10,000 child-months) and before the first deployment for medical diagnoses of maltreatment (3.78 episodes per 10,000 child-months). CONCLUSIONS: We confirmed an elevated risk for child maltreatment during deployment but also found a previously unidentified high-risk period during the 6 months following deployment, indicating elevated stress within families of deployed and returning soldiers. These findings can inform efforts by the military to initiate and standardize support and preparation to families during periods of elevated risk. PMID- 26562131 TI - Systematic Motorcycle Management and Health Care Delivery: A Field Trial. AB - OBJECTIVES: We investigated whether managed transportation improves outreach based health service delivery to rural village populations. METHODS: We examined systematic transportation management in a small-cluster interrupted time series field trial. In 8 districts in Southern Zambia, we followed health workers at 116 health facilities from September 2011 to March 2014. The primary outcome was the average number of outreach trips per health worker per week. Secondary outcomes were health worker productivity, motorcycle performance, and geographical coverage. RESULTS: Systematic fleet management resulted in an increase of 0.9 (SD = 1.0) trips to rural villages per health worker per week (P < .001), village level health worker productivity by 20.5 (SD = 5.9) patient visits, 10.2 (SD = 1.5) measles immunizations, and 5.2 (SD = 5.4) child growth assessments per health worker per week. Motorcycle uptime increased by 3.5 days per week (P < .001), use by 1.5 days per week (P < .001), and mean distance by 9.3 kilometers per trip (P < .001). Geographical coverage of health outreach increased in experimental (P < .001) but not control districts. CONCLUSIONS: Systematic motorcycle management improves basic health care delivery to rural villages in resource-poor environments through increased health worker productivity and greater geographical coverage. PMID- 26562132 TI - Northridge and Coupey Respond. PMID- 26562127 TI - Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation. OBJECTIVES: We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population. SEARCH METHODS: An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts. SELECTION CRITERIA: Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party. DATA COLLECTION AND ANALYSIS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (alpha level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent. RESULTS: Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies. CONCLUSIONS: Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation. PMID- 26562130 TI - Correlates of Sexual HIV Risk Among African American Men Who Have Sex With Men. AB - OBJECTIVES: We examined correlates of condomless anal intercourse with nonmain sexual partners among African American men who have sex with men (MSM). METHODS: We recruited social networks composed of 445 Black MSM from 2012 to 2014 in Milwaukee, Wisconsin; Cleveland, Ohio; and Miami Beach, Florida. Participants reported past-3-month sexual behavior, substance use, and background, psychosocial, and HIV-related characteristics. RESULTS: Condomless anal intercourse outside main concordant partnerships, reported by 34.4% of MSM, was less likely in the case of no alcohol and marijuana use in the past 30 days, and higher risk-reduction behavioral intentions. High frequency of condomless anal intercourse acts with nonmain partners was associated with high gay community participation, weak risk-reduction intentions, safer sex not being perceived as a peer norm, low condom-use self-efficacy, and longer time since most recent HIV testing. CONCLUSIONS: Condomless anal intercourse with nonmain partners among Black MSM was primarily associated with gay community participation, alcohol and marijuana use, and risk-reduction behavioral intentions. PMID- 26562133 TI - Local weighting of nanometric track structure properties in macroscopic voxel geometries for particle beam treatment planning. AB - The research project BioQuaRT within the European Metrology Research Programme aimed at correlating ion track structure characteristics with the biological effects of radiation and developed measurement and simulation techniques for determining ion track structure on different length scales from about 2 nm to about 10 MUm. Within this framework, we investigated methods to translate track structure quantities derived on a nanometre scale to macroscopic dimensions. Here we make use of parameterizations that link the energy of the projectile to the ionization pattern of the track using nanodosimetric ionization cluster size distributions. They were defined with data generated by simulations of ion tracks in liquid water using the Geant4 Monte Carlo toolkit with the Geant4-DNA processes. For the clinical situation with a mixed radiation field, where particles of various energies hit a cell from several directions, we have to find macroscopic relevant mean values. They can be determined by appropriate local weighting functions for the identified parameterization. We show that a stopping power weighted mean value of the mentioned track structure properties can describe the overall track structure in a cell exposed to a mixed radiation field. The parameterization, together with the presented stopping power weighting approach, show how nanometric track structure properties could be integrated into treatment planning systems without the need to perform time consuming simulations on the nanometer level for each individual patient. PMID- 26562134 TI - Nb and Ta layer doping effects on the interfacial energetics and electronic properties of LaAlO3/SrTiO3 heterostructure: first-principles analysis. AB - The two-dimensional electron gas (2DEG) formed at the n-type (LaO)(+1)/(TiO2)(0) interface in the polar/nonpolar LaAlO3/SrTiO3 (LAO/STO) heterostructure (HS) has emerged as a prominent research area because of its great potential for nanoelectronic applications. Due to its practical implementation in devices, desired physical properties such as high charge carrier density and mobility are vital. In this respect, 4d and 5d transition metal doping near the interfacial region is expected to tailor electronic properties of the LAO/STO HS system effectively. Herein, we studied Nb and Ta-doping effects on the energetics, electronic structure, interfacial charge carrier density, magnetic moment, and the charge confinements of the 2DEG at the n-type (LaO)(+1)/(TiO2)(0) interface of LAO/STO HS using first-principles density functional theory calculations. We found that the substitutional doping of Nb(Ta) at Ti [Nb(Ta)@Ti] and Al [Nb(Ta)@Al] sites is energetically more favorable than that at La [Nb(Ta)@La] and Sr [Nb(Ta)@Sr] sites, and under appropriate thermodynamic conditions, the changes in the interfacial energy of HS systems upon Nb(Ta)@Ti and Nb(Ta)@Al doping are negative, implying that the formation of these structures is energetically favored. Our calculations also showed that Nb(Ta)@Ti and Nb(Ta)@Al doping significantly improve the interfacial charge carrier density with respect to that of the undoped system, which is because the Nb(Ta) dopant introduces excess free electrons into the system, and these free electrons reside mainly on the Nb(Ta) ions and interfacial Ti ions. Hence, along with the Ti 3d orbitals, the Nb 4d and Ta 5d orbitals also contribute to the interfacial metallic states; accordingly, the magnetic moments on the interfacial Ti ions increase significantly. As expected, the Nb@Al and Ta@Al doped LAO/STO HS systems show higher interfacial charge carrier density than the undoped and other doped systems. In contrast, Nb@Ti and Ta@Ti doped systems may show higher charge carrier mobility because of the lower electron effective mass. PMID- 26562135 TI - [Correlation from Undiluted Vitreous Cytokines of Untreated Central Retinal Vein Occlusion with Spectral Domain Optical Coherence Tomography]. AB - PURPOSE: To correlate key inflammatory and pro-angiogenic cytokines from undiluted vitreous fluid of treatment-naive patients with central retinal vein occlusion (CRVO) with SD-OCT parameters. METHODS: Thirty-five patients (age 71.1 years, 24 phakic, 30 non-ischaemic) underwent intravitreal combination therapy, including single-site 23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non-uveitis floaterectomy served as controls. Levels of interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF-A) were correlated with visual acuity (logMar), category of CRVO (ischaemic or non-ischaemic) and morphological parameters, such as central macular thickness (CMT), thickness of neurosensory retina (Tneuro), extent of serous retinal detachment (SRT) and disintegrity of the IS/OS and others. RESULTS: Mean IL-6 was 64.7 pg/ml (SD +/- 115.8), mean MCP-1 1015.7 pg/ml (+/- 970.1), and mean VEGF-A 278.4 pg/ml (+/- 512.8), which was significantly higher than the control values of IL-6 6.2 +/- 3.4 pg/ml (p = 0.06), MCP-1 253.2 +/- 73.5 pg/ml (p < 0.0 000 001) and VEGF-A 7.0 +/- 4.9 pg/ml (p < 0.0006), respectively. All cytokines correlated highly with one another (correlation coefficient r = 0.82 for IL-6 and MCP-1; r = 0.68 for Il-6 and VEGF-A; r = 0.64 for MCP-1 and VEGF-A). IL-6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated significantly with SRT, dIS/OS, and dELM. VEGF-A did not correlate with changes in SD-OCT, while it had a trend to be higher in the ischaemic versus the non-ischaemic CRVO groups (p = 0.09). CONCLUSIONS: The inflammatory cytokines were more often correlated with morphological changes assessed by SD-OCT, whereas VEGF-A did not correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not be sufficient to decrease the inflammatory response in CRVO therapy. PMID- 26562136 TI - [Effectiveness of Intravitreal Aflibercept Injections in Patients who had Received 10 and More Ranibizumab Injections in Advance]. AB - BACKGROUND: Since 2007, the standard treatment for age related macular degeneration has been intravitreal injection of ranibizumab. However, despite continuous treatment, some patients fail to achieve remission or stabilisation of the disease. Since 2012, the recombinant fusion protein aflibercept has been available as an alternative treatment. In this study, we investigated whether patients who appear to be resistant to ranibizumab would benefit from treatment with aflibercept. METHODOLOGY: This retrospective study covered 83 eyes of 81 patients, for whom treatment switch from ranibizumab to aflibercept was indicated. Inclusion criteria were an age >= 50 years and at least 10 ranibizumab injections before a switch to aflibercept. Patients with severely impaired visual acuity were excluded. Primary outcomes were improvement or loss of visual acuity (VA) and evaluation of central macular thickness (CMT) via SD-OCT. Secondary endpoints were percentage of eyes without activity of the choroidal neovascular membrane after aflibercept injections and loss or gain of letters on the visual chart. Statistical analysis was performed using SPSS. RESULTS: VA was 0.83 +/- 0.34 logMAR before the first aflibercept injection, with a slight but not statistically significant improvement up to 0.79 +/- 0.33 logMAR after the third aflibercept injection (p = 0.205). On the other hand, there was a clear reduction of CMT in OCT, from 451.4 +/- 263.0 to 288.2 +/- 128.2 um (p = 0.0001). Overall, 73 % of eyes exhibited better or stable VA and 27 % of eyes lost VA. Interestingly, eyes with worse initial VA gained greater benefit from the switch to aflibercept (p = 0.001). CONCLUSION: A switch to aflibercept may lead to stabilisation of choroidal neovascularisation and thus stabilise the visual acuity for patients who appear to be no longer responsive to treatment with ranibizumab. PMID- 26562137 TI - A systematic review of the status of children's school access in low- and middle income countries between 1998 and 2013: using the INDEPTH Network platform to fill the research gaps. AB - BACKGROUND: The framework for expanding children's school access in low- and middle-income countries (LMICs) has been directed by universal education policies as part of Education for All since 1990. In measuring progress to universal education, a narrow conceptualisation of access which dichotomises children's participation as being in or out of school has often been assumed. Yet, the actual promise of universal education goes beyond this simple definition to include retention, progression, completion, and learning. OBJECTIVE: Our first objective was to identify gaps in the literature on children's school access using the zones of exclusion of the Consortium for Research on Educational Access, Transition, and Equity as a framework. Second, we gave consideration to how these gaps can be met by using longitudinal and cross-country data from Health and Demographic Surveillance System (HDSS) sites within the International Network for the Demographic Evaluation of Population and Their Health (INDEPTH) in LMICs. DESIGN: Using Web of Science, we conducted a literature search of studies published in international peer-reviewed journals between 1998 and 2013 in LMICs. The phrases we searched included six school outcomes: school enrolment, school attendance, grade progression, school dropout, primary to secondary school transition, and school completion. From our search, we recorded studies according to: 1) school outcomes; 2) whether longitudinal data were used; and 3) whether data from more than one country were analysed. RESULTS: The area of school access most published is enrolment followed by attendance and dropout. Primary to secondary school transition and grade progression had the least number of publications. Of 132 publications which we found to be relevant to school access, 33 made use of longitudinal data and 17 performed cross-country analyses. CONCLUSIONS: The majority of studies published in international peer-reviewed journals on children's school access between 1998 and 2013 were focused on three outcomes: enrolment, attendance, and dropout. Few of these studies used data collected over time or data collected from more than one country for comparative analyses. The contribution of the INDEPTH Network in helping to address these gaps in the literature lies in the longitudinal design of HDSS surveys and in the diversity of countries within the network. PMID- 26562138 TI - Trends in contraceptive use and distribution of births with demographic risk factors in Ethiopia: a sub-national analysis. AB - BACKGROUND: Evidence shows that family planning contributes to the decline in child mortality by decreasing the proportions of births that are considered high risk. The main objective of the present analysis was to examine the trends in use of modern contraceptives and their relationship with total fertility rate (TFR) and distribution of births by demographic risk factors as defined by mother's age, birth interval, and birth order at the sub-national level in Ethiopia. DESIGN: Analyses used data from three Demographic and Health Surveys in Ethiopia (2000, 2005, and 2011), which are nationally representative data collected through questionnaire-based interviews from women 15-49 using a stratified, two stage cluster sampling. First, we examined the trends of and relationship between TFR (in the 3 years before each survey) and modern contraceptive use among currently married women in all administrative regions over the time period 2000 2011 using linear regression analysis. We also examined the relationship between birth risks and under-five mortality using the no-risk group as a reference. Finally, multiple logistic regression analysis was performed to estimate the relationship between the effect of being a resident in one of the regions and having an avoidable birth risk (which includes births to mothers younger than 18 and older than 34 years, birth interval of less than 24 months and birth order higher than third) after adjusting for select covariates including wealth, educational status, residence, religion and exposure to family planning information. RESULTS: Sub-national-level regression analysis showed an inverse relationship between modern contraceptive use among married women and the TFR, with an average decrease of TFR by one child per woman associated with a 13 percentage point increase in modern contraceptive use between 2000 and 2011. A high percentage of births in Ethiopia (62%) fall in one of the risk categories (excluding first births), with wide regional variation from 55% in Gambela to 72% in the Somali region. The multivariate analysis showed women living in the Somali, Afar and Benishangul-Gumuz regions had significantly higher odds of having avoidable birth risk compared to those in Addis Ababa after controlling for observed covariates. The trend analysis showed there was a significant drop in the proportion of births from women above 34 years between 2000 and 2011. There was no significant decline in births to women less than 18 years between 2000 and 2011. CONCLUSIONS: A majority of births in Ethiopia fall in one of the risk categories, with substantial region-to-region variation in the percentage of births with avoidable risk factors, Somali and Afar having the highest burden. The analysis indicated that births in the three regions had significantly higher odds of having one of the avoidable risk factors compared to Addis Ababa, and we suggest family planning programmes need to identify differentials of modern contraceptive use at the sub-national level in order to better address coverage and equity issues. PMID- 26562139 TI - Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality. AB - BACKGROUND: Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. OBJECTIVES: Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. DESIGN: We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18-23 months, 24-35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta analysis with random survey effects. RESULTS: We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard regression adjustment for confounding factors estimated a risk ratio for neonatal mortality of 2.28 (95% confidence interval: 2.18-2.37). This same effect estimated within mother is 1.57 (95% confidence interval: 1.52-1.63), a decline of almost one-third in the effect on neonatal mortality. CONCLUSIONS: Neonatal, infant, and child mortality are strongly and significantly related to preceding birth interval, where births within a short interval of time after the previous birth have increased mortality. Previous analyses have demonstrated this relationship on average across all births; however, women who have short spaces between births are different from women with long spaces. Among women 35 years and older where a comparison of birth spaces within mother is possible, we find a much reduced although still significant effect of short birth spaces on child mortality. PMID- 26562140 TI - Meeting demand for family planning within a generation: prospects and implications at country level. AB - BACKGROUND: In order to track progress towards the target of universal access to sexual and reproductive health care services of the post-2015 Sustainable Development Goals (SDGs), a measure (demand for family planning satisfied with modern contraceptive methods) and a benchmark (at least 75% by 2030 in all countries) have been recommended. OBJECTIVES: The goal of this study was to assess the prospects of reaching the benchmark at the country level. Such information can facilitate strategic planning, including resource allocation at global and country levels. DESIGN: We selected 63 countries based on their status as least developed according to the United Nations or as a priority country in global family planning initiatives. Using United Nations estimates and projections of family planning indicators between 1970 and 2030, we calculated percent demand for family planning satisfied with modern contraceptive methods for each year and country. We then calculated the annual percentage point changes between 2014 and 2030 required to meet the benchmark. The required rates of change were compared to current projections as well as estimates between 1970 and 2010. RESULTS: To reach the benchmark on average across the 63 countries, demand satisfied with modern methods must increase by 2.2 percentage points per year between 2014 and 2030 - more than double current projections. Between 1970 and 2010, such rapid progress was observed in 24 study countries but typically spanning 5-10 years. At currently projected rates, only 9 of the 63 study countries will reach the benchmark. Meanwhile, the gap between projected and required changes is largest in the Central and West African regions, 0.9 and 3.0 percentage points per year, respectively. If the benchmark is achieved, 334 million women across the study countries will use a modern contraceptive method in 2030, compared to 226 million women in 2014. CONCLUSIONS: In order to achieve the component of the SDGs calling for universal access to sexual and reproductive health services, substantial effort is needed to accelerate rates of progress by a factor of 2 in most study countries and by a factor of 3 in Central and West African countries. PMID- 26562141 TI - Estimating family planning coverage from contraceptive prevalence using national household surveys. AB - BACKGROUND: Contraception is one of the most important health interventions currently available and yet, many women and couples still do not have reliable access to modern contraceptives. The best indicator for monitoring family planning is the proportion of women using contraception among those who need it. This indicator is frequently called demand for family planning satisfied and we argue that it should be called family planning coverage (FPC). This indicator is complex to calculate and requires a considerable number of questions to be included in a household survey. OBJECTIVES: We propose a model that can predict FPC from a much simpler indicator - contraceptive use prevalence - for situations where it cannot be derived directly. DESIGN: Using 197 Multiple Indicator Cluster Surveys and Demographic and Health Surveys from 82 countries, we explored least squares regression models that could be used to predict FPC. Non-linearity was expected in this situation and we used a fractional polynomial approach to find the best fitting model. We also explored the effect of calendar time and of wealth on the models explored. RESULTS: Given the high correlation between the variables involved in FPC, we managed to derive a relatively simple model that depends only on contraceptive use prevalence but explains 95% of the variability of the outcome, with high precision for the estimated regression line. We also show that the relationship between the two variables has not changed with time. A concordance analysis showed agreement between observed and fitted results within a range of +/-9 percentage points. CONCLUSIONS: We show that it is possible to obtain fairly good estimates of FPC using only contraceptive prevalence as a predictor, a strategy that is useful in situations where it is not possible to estimate FPC directly. PMID- 26562142 TI - Trends and patterns of modern contraceptive use and relationships with high-risk births and child mortality in Burkina Faso. AB - BACKGROUND: In sub-Saharan Africa, few studies have stressed the importance of spatial heterogeneity analysis in modern contraceptive use and the relationships with high-risk births. OBJECTIVE: This paper aims to analyse the association between modern contraceptive use, distribution of birth risk, and under-five child mortality at both national and regional levels in Burkina Faso. DESIGN: The last three Demographic and Health Surveys - conducted in Burkina Faso in 1998, 2003, and 2010 - enabled descriptions of differentials, trends, and associations between modern contraceptive use, total fertility rates (TFR), and factors associated with high-risk births and under-five child mortality. Multivariate models, adjusted by covariates of cultural and socio-economic background and contact with health system, were used to investigate the relationship between birth risk factors and modern contraceptive prevalence rates (mCPR). RESULTS: Overall, Burkina Faso's modern contraception level remains low (15.4% in 2010), despite significant increases during the last decade. However, there are substantial variations in mCPR by region, and health facility contact was positively associated with mCPR increase. Women's fertility history and cultural and socio-economic background were also significant factors in predicting use of modern contraception. Low modern contraceptive use is associated with higher birth risks and increased child mortality. This association is stronger in the Sahel, Est, and Sud-Ouest regions. Even though all factors in high-risk births were associated with under-five mortality, it should be stressed that short birth spacing ranked as the highest risk in relation to mortality of children. CONCLUSIONS: Programmes that target sub-national differentials and leverage women's health system contacts to inform women about family planning opportunities may be effective in improving coverage, quality, and equity of modern contraceptive use. Improving the demand satisfied for modern contraception may result in a reduction in the percentage of women experiencing high-risk births and may also reduce child mortality. PMID- 26562143 TI - Patterns and trends of contraceptive use among sexually active adolescents in Burkina Faso, Ethiopia, and Nigeria: evidence from cross-sectional studies. AB - BACKGROUND: The benefits of universal access to voluntary contraception have been widely documented in terms of maternal and newborn survival, women's empowerment, and human capital. Given population dynamics, the choices and opportunities adolescents have in terms of access to sexual and reproductive health information and services could significantly affect the burden of diseases and nations' human capital. OBJECTIVES: The objectives of this paper are to assess the patterns and trends of modern contraception use among sexually active adolescents by socio economic characteristics and by birth spacing and parity; to explore predictors of use of modern contraception in relation to the health system; and to discuss implications of the findings for family planning policy and programmes. DESIGN: Data are from the last three Demographic and Health Surveys of Ethiopia, Burkina Faso, and Nigeria. The descriptive analysis focused on sexually active adolescents (15- to 19-year age group), used modern contraception as the dependent variable, and a series of contact points with the health system (antenatal care, institutional delivery, postnatal care, immunisation) as covariates. The multivariate analysis used the same covariates, adjusting for socio-economic variables. RESULTS: There are two different groups of sexually active adolescents: those married or in a union with very low use of modern contraception and lower socio-economic status, and those unmarried, among whom nearly 50% are using modern contraception. Younger adolescents have lower modern contraceptive prevalence. There are significant inequality issues in modern contraception use by education, residence, and wealth quintile. However, while there was no significant progress in Burkina Faso and Nigeria, the data in Ethiopia point to a significant and systematic reduction of inequalities. The narrowing of the equity gap was most notable for childbearing adolescents with no education or living in rural areas. In the three countries, after adjusting for socio-economic variables, the strongest factors affecting modern contraception use among childbearing adolescents were marriage and child immunisation. CONCLUSIONS: Addressing child marriage and adopting effective policies and strategies to reach married adolescents are critical for improving empowerment and human capital of adolescent girls. The reduction of the equity gap in coverage in Ethiopia warrants further studies and documentation. The results suggest a missed opportunity for maternal and newborn and family planning integration. PMID- 26562144 TI - Patterns and trends of postpartum family planning in Ethiopia, Malawi, and Nigeria: evidence of missed opportunities for integration. AB - BACKGROUND: The first 12 months following childbirth are a period when a subsequent pregnancy holds the greatest risk for mother and baby, but also when there are numerous contacts with the healthcare system for postnatal care for mother and baby (immunisation, nutrition, etc.). The benefits and importance of postpartum family planning are well documented. They include a reduction in risk of miscarriage, as well as mitigation of (or protection against) low birth weight, neonatal and maternal death, preterm birth, and anaemia. OBJECTIVES: The objectives of this paper are to assess patterns and trends in the use of postpartum family planning at the country level, to determine whether postpartum family planning is associated with birth interval and parity, and to identify the health services most closely associated with postpartum family planning after adjusting for socio-economic characteristics. DESIGN: Data were used from Demographic and Health Surveys that contain a reproductive calendar, carried out within the last 10 years, from Ethiopia, Malawi, and Nigeria. All women for whom the calendar was completed and who gave birth between 57 and 60 months prior to data collection were included in the analysis. For each of the births, we merged the reproductive calendar with the birth record into a survey for each country reflecting the previous 60 months. The definition of the postpartum period in this paper is based on a period of 3 months postpartum. We used this definition to assess early adoption of postpartum family planning. We assessed variations in postpartum family planning according to demographic and socio-economic variables, as well as its association with various contact opportunities with the health system [antenatal care (ANC), childbirth in facilities, immunisation, etc.]. We did simple descriptive analysis with tabular, graphic, and 'equiplot' displays and a logistic regression controlling for important background characteristics. RESULTS: Overall, variation in postpartum use of modern contraception was not affected over the years by age or marital status. One contrast to this is in Ethiopia, where the data show a significant increase in uptake of postpartum contraception among adolescents from 2005 to 2011. There are systematic and pervasive equity issues in the use of modern postpartum family planning by education level, place of residence, and wealth quintile, especially in Ethiopia where the gaps are very large. Disaggregation of data also point to significant sub-national variations. After adjusting for socio-economic variables, the most consistent health sector services associated with modern postpartum contraception are institutional childbirth and child immunisation. ANC is less likely to be associated with the use of modern postpartum family planning. CONCLUSION: Postpartum use of modern family planning has remained very low over the years, including for childbearing adolescents. Our results indicate that improving postpartum family planning requires policies and strategies to address the inequalities caused by socio-economic factors and the integration of family planning with maternal and newborn health services, particularly with childbirth in facilities and child immunisation. Scaling up systematic screening, training of providers, and generation of demand are some possible ways forward. PMID- 26562145 TI - Contraceptive use and distribution of high-risk births in Nigeria: a sub-national analysis. AB - BACKGROUND: Family planning expansion has been identified as an impetus to harnessing Nigeria's demographic dividend. However, there is a need for data to address pockets of inequality and to better understand cultural and social factors affecting contraceptive use and health benefits. This paper contributes to addressing these needs by providing evidence on the trends and sub-national patterns of modern contraceptive prevalence in Nigeria and the association between contraceptive use and high-risk births in Nigeria. DESIGN: The study utilised women's data from the last three Demographic and Health Surveys (2003, 2008, and 2013) in Nigeria. The analysis involved descriptive, bivariate, and multivariate analyses. The multivariate analyses were performed to examine the relationship between high-risk births and contraceptive use. Associations were examined using Poisson regression. RESULTS: Findings showed that respondents in avoidable high-risk birth categories were less likely to use contraceptives compared to those at no risk [rate ratio 0.82, confidence interval: 0.76-0.89, p<0.001]. Education and wealth index consistently predicted significant differences in contraceptive use across the models. CONCLUSIONS: The results of this study suggest that women in the high-risk birth categories were significantly less likely to use a modern method of contraception relative to those categorised as having no risk. However, there are huge sub-national variations at regional and state levels in contraceptive prevalence and subsequent high-risk births. These results further strengthen evidence-based justification for increased investments in family planning programmes at the state and regional levels, particularly regions and states with high unmet needs for family planning. PMID- 26562146 TI - Implementation of a phased medical educational approach in a developing country. AB - OBJECTIVE: Healthcare provider education can serve as one method for improving healthcare in developing countries. Working with providers at St Luke Hospital in Haiti, we developed a phased educational approach through partnership development, face-to-face teaching, and virtual educational tools. DESIGN: Our novel approach included three phases: direct patient care, targeted education, and utilization of the train-the-trainer model. Our end goal was an educational system that could be utilized by the local medical staff to continually improve their medical knowledge, even after our educational project was completed. We implemented pre- and post-lecture evaluations during our teaching phase to determine whether the education provided was effective and beneficial. Additionally, we provided medical lectures on a shared file internet platform, Box.com, during the train-the-trainer phase to allow healthcare providers in Haiti to access the educational content electronically. RESULTS: In total, 47 lectures were given to 150 medical providers, including nurses, physicians, and pharmacists. Pre- and post-lecture evaluations were administered. The mean was 30.63 (14.40) for pre-lecture evaluations and 93.36 (9.80) for post-lecture evaluations indicating improvement out of a total of 100 possible points. Our collaborative Box.com account contains 214 medical education lectures available for viewing as a constant resource to St Luke Hospital staff. Thus far, 20 of the 43 (47%) Haitian medical providers have viewed lectures, with an average of 5.6 lectures viewed per person. Qualitative data suggest that these methods improved communication between healthcare staff, promoted better ways of triaging patients, and improved job satisfaction. CONCLUSIONS: A phased educational approach can improve healthcare workers' knowledge through partnership in a developing country. Educating local providers is one way of ensuring that in country healthcare staff will improve their medical knowledge and expertise. PMID- 26562147 TI - Family planning as a critical component of sustainable global development. PMID- 26562149 TI - Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function. AB - Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis-related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage. PMID- 26562150 TI - Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations. AB - To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of>6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti-acetylcholine receptor [AChR] antibody positive; onset age>=50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 * 10-7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 * 10-10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 * 10-6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 versus ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 * 10-12) versus 2.82 in EOMG (P = 3.86 * 10-45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG. PMID- 26562152 TI - VMCast: A VM-Assisted Stability Enhancing Solution for Tree-Based Overlay Multicast. AB - Tree-based overlay multicast is an effective group communication method for media streaming applications. However, a group member's departure causes all of its descendants to be disconnected from the multicast tree for some time, which results in poor performance. The above problem is difficult to be addressed because overlay multicast tree is intrinsically instable. In this paper, we proposed a novel stability enhancing solution, VMCast, for tree-based overlay multicast. This solution uses two types of on-demand cloud virtual machines (VMs), i.e., multicast VMs (MVMs) and compensation VMs (CVMs). MVMs are used to disseminate the multicast data, whereas CVMs are used to offer streaming compensation. The used VMs in the same cloud datacenter constitute a VM cluster. Each VM cluster is responsible for a service domain (VMSD), and each group member belongs to a specific VMSD. The data source delivers the multicast data to MVMs through a reliable path, and MVMs further disseminate the data to group members along domain overlay multicast trees. The above approach structurally improves the stability of the overlay multicast tree. We further utilized CVM-based streaming compensation to enhance the stability of the data distribution in the VMSDs. VMCast can be used as an extension to existing tree-based overlay multicast solutions, to provide better services for media streaming applications. We applied VMCast to two application instances (i.e., HMTP and HCcast). The results show that it can obviously enhance the stability of the data distribution. PMID- 26562151 TI - Evolution and Emergence of Enteroviruses through Intra- and Inter-species Recombination: Plasticity and Phenotypic Impact of Modular Genetic Exchanges in the 5' Untranslated Region. AB - Genetic recombination shapes the diversity of RNA viruses, including enteroviruses (EVs), which frequently have mosaic genomes. Pathogenic circulating vaccine-derived poliovirus (cVDPV) genomes consist of mutated vaccine poliovirus (PV) sequences encoding capsid proteins, and sequences encoding nonstructural proteins derived from other species' C EVs, including certain coxsackieviruses A (CV-A) in particular. Many cVDPV genomes also have an exogenous 5' untranslated region (5' UTR). This region is involved in virulence and includes the cloverleaf (CL) and the internal ribosomal entry site, which play major roles in replication and the initiation of translation, respectively. We investigated the plasticity of the PV genome in terms of recombination in the 5' UTR, by developing an experimental model involving the rescue of a bipartite PV/CV-A cVDPV genome rendered defective by mutations in the CL, following the co-transfection of cells with 5' UTR RNAs from each of the four human EV species (EV-A to -D). The defective cVDPV was rescued by recombination with 5' UTR sequences from the four EV species. Homologous and nonhomologous recombinants with large deletions or insertions in three hotspots were isolated, revealing a striking plasticity of the 5' UTR. By contrast to the recombination of the cVDPV with the 5' UTR of group II (EV-A and -B), which can decrease viral replication and virulence, recombination with the 5' UTRs of group I (EV-C and -D) appeared to be evolutionarily neutral or associated with a gain in fitness. This study illustrates how the genomes of positive-strand RNA viruses can evolve into mosaic recombinant genomes through intra- or inter-species modular genetic exchanges, favoring the emergence of new recombinant lineages. PMID- 26562153 TI - Pimecrolimus Is a Potent Inhibitor of Allergic Reactions to Hymenopteran Venom Extracts and Birch Pollen Allergen In Vitro. AB - Pimecrolimus (Elidel, SDZ ASM 981) is an anti-inflammatory and immunomodulatory 33-epichloro-derivative of macrolactam ascomycin, with low potential for affecting systemic immune responses compared with other calcineurin inhibitors, cyclosporin A and tacrolimus. Despite numerous studies focused on the mechanism of pimecrolimus action on mast cells, only the single report has addressed pimecrolimus effects on other typical FcepsilonRI-expressing cells, the basophils. Patients allergic to birch pollen (n = 20), hymenopteran venoms (n = 23) and 10 non-allergic volunteers were examined. Primary human basophils pre treated or not with 0.5-50 MUMol pimecrolimus were exposed to various concentrations of recombinant Bet v 1a allergen, bee or wasp venom extracts and anti-IgE for 20 min, and then examined for the expression of CD45, CD193, CD203c, CD63 and CD164 using flow cytometry. The externalization of basophil activation markers (CD63 and CD164) was equally inhibited through pimecrolimus in cells activated by recombinant pollen allergen, hymenopteran venom extracts and anti IgE. Although the individual response rate was subject to strong variation, importantly, pre-treatment with pimecrolimus lowered the number of activated basophils in response to any of the stimuli in the basophils from all patients. The inhibition was concentration-dependent; approximately half of the basophils were inhibited in the presence of 2.5 mMol pimecrolimus. Pimecrolimus is a valuable new tool for the inhibition of hyper-reactive basophils in patients with pollen allergy and a history of anaphylactic reactions to bee or wasp venoms. Further research should address short-term use of pimecrolimus in vivo in a wide spectrum of allergic diseases. PMID- 26562154 TI - Etiology of Multiple Non-EV71 and Non-CVA16 Enteroviruses Associated with Hand, Foot and Mouth Disease in Jinan, China, 2009-June 2013. AB - Hand, foot, and mouth disease (HFMD) is an infectious disease caused by human enterovirus 71 (EV71), coxsackievirus A16 (CVA16) and other enteroviruses. It is of interest that other enteroviruses associated with HFMD in Jinan have been rarely reported. The aim of the present study is to detect and characterize the circulating serotypes of non-EV71 and non-CVA16 enteroviruses associated with HFMD in Jinan city, Shandong province, China. A total of 400 specimens were collected from clinically diagnosed HFMD cases in Jinan from January 2009 to June 2013. All specimens were infected with non-EV71 and non-CVA16 enteroviruses previously confirmed by RT-PCR or real-time PCR according to the protocols at that time. The GeXP-based multiplex RT-PCR assay (GeXP assay) was performed to investigate the pathogen spectrum of 15 enteroviruses (coxsackieviruses A4, A5, A6, A9, A10, A16; coxsackieviruses B1, B3, B5; Echoviruses 6, 7, 11, 13, 19 and EV71) infections associated with HMFD. For GeXP assay negative samples, reverse transcription nested PCR (nested RT-PCR) based on the 5' -untranslated region (5' UTR) sequence and phylogenetic analysis were conducted to further explore the etiology of multiple enteroviruses. The results showed that a total of twenty serotypes of enteroviruses (including EV71 and CVA16) were identified by GeXP assay and nested RT-PCR. The most circulating twelve serotypes of enteroviruses with HFMD in Jinan from 2009 to June 2013 were EV71, CVA16, CVA10, CVA6, CVA12, CVA2, Echo3, CVA4, CVA9, CVB1, CVB3 and Echo6. CVA10 and CVA6 were the most prevalent pathogens other than EV71 and CVA16 in Jinan and their most prevalent seasons were spring and summer, and a slight increase was observed in autumn and early winter. It should be noted that mixed-infections were identified by GeXP assay and the phylogenetic tree clearly discriminated the multiple pathogens associated with HFMD. Our results thus demonstrate that there was a clear lack of a reliable testing method for EV71 and CVA16 and multiple non-EV71 and non-CVA16 enteroviruses associated with HFMD were present in Jinan. The GeXP assay combined with nested RT-PCR based on 5'-UTR region could meet the need for the national surveillance of multiple enteroviruses or the investigation of epidemic outbreaks triggered by enteroviruses in the future. PMID- 26562155 TI - Triploidy--Observations in 154 Diandric Cases. AB - Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0-1,4%). PMID- 26562156 TI - Outcome-Driven Cluster Analysis with Application to Microarray Data. AB - One goal of cluster analysis is to sort characteristics into groups (clusters) so that those in the same group are more highly correlated to each other than they are to those in other groups. An example is the search for groups of genes whose expression of RNA is correlated in a population of patients. These genes would be of greater interest if their common level of RNA expression were additionally predictive of the clinical outcome. This issue arose in the context of a study of trauma patients on whom RNA samples were available. The question of interest was whether there were groups of genes that were behaving similarly, and whether each gene in the cluster would have a similar effect on who would recover. For this, we develop an algorithm to simultaneously assign characteristics (genes) into groups of highly correlated genes that have the same effect on the outcome (recovery). We propose a random effects model where the genes within each group (cluster) equal the sum of a random effect, specific to the observation and cluster, and an independent error term. The outcome variable is a linear combination of the random effects of each cluster. To fit the model, we implement a Markov chain Monte Carlo algorithm based on the likelihood of the observed data. We evaluate the effect of including outcome in the model through simulation studies and describe a strategy for prediction. These methods are applied to trauma data from the Inflammation and Host Response to Injury research program, revealing a clustering of the genes that are informed by the recovery outcome. PMID- 26562157 TI - Leptospirosis in Rio Grande do Sul, Brazil: An Ecosystem Approach in the Animal Human Interface. AB - BACKGROUND: Leptospirosis is an epidemic-prone neglected disease that affects humans and animals, mostly in vulnerable populations. The One Health approach is a recommended strategy to identify drivers of the disease and plan for its prevention and control. In that context, the aim of this study was to analyze the distribution of human cases of leptospirosis in the State of Rio Grande do Sul, Brazil, and to explore possible drivers. Additionally, it sought to provide further evidence to support interventions and to identify hypotheses for new research at the human-animal-ecosystem interface. METHODOLOGY AND FINDINGS: The risk for human infection was described in relation to environmental, socioeconomic, and livestock variables. This ecological study used aggregated data by municipality (all 496). Data were extracted from secondary, publicly available sources. Thematic maps were constructed and univariate analysis performed for all variables. Negative binomial regression was used for multivariable statistical analysis of leptospirosis cases. An annual average of 428 human cases of leptospirosis was reported in the state from 2008 to 2012. The cumulative incidence in rural populations was eight times higher than in urban populations. Variables significantly associated with leptospirosis cases in the final model were: Parana/Paraiba ecoregion (RR: 2.25; CI95%: 2.03-2.49); Neossolo Litolitico soil (RR: 1.93; CI95%: 1.26-2.96); and, to a lesser extent, the production of tobacco (RR: 1.10; CI95%: 1.09-1.11) and rice (RR: 1.003; CI95%: 1.002-1.04). CONCLUSION: Urban cases were concentrated in the capital and rural cases in a specific ecoregion. The major drivers identified in this study were related to environmental and production processes that are permanent features of the state. This study contributes to the basic knowledge on leptospirosis distribution and drivers in the state and encourages a comprehensive approach to address the disease in the animal-human-ecosystem interface. PMID- 26562158 TI - MzPIP2;1: An Aquaporin Involved in Radial Water Movement in Both Water Uptake and Transportation, Altered the Drought and Salt Tolerance of Transgenic Arabidopsis. AB - BACKGROUND: Plants are unavoidably subjected to various abiotic stressors, including high salinity, drought and low temperature, which results in water deficit and even death. Water uptake and transportation play a critical role in response to these stresses. Many aquaporin proteins, localized at different tissues, function in various transmembrane water movements. We targeted at the key aquaporin in charge of both water uptake in roots and radial water transportation from vascular tissues through the whole plant. RESULTS: The MzPIP2;1 gene encoding a plasma membrane intrinsic protein was cloned from salt tolerant apple rootstock Malus zumi Mats. The GUS gene was driven by MzPIP2;1 promoter in transgenic Arabidopsis. It indicated that MzPIP2;1 might function in the epidermal and vascular cells of roots, parenchyma cells around vessels through the stems and vascular tissues of leaves. The ectopically expressed MzPIP2;1 conferred the transgenic Arabidopsis plants enhanced tolerance to slight salt and drought stresses, but sensitive to moderate salt stress, which was indicated by root length, lateral root number, fresh weight and K+/Na+ ratio. In addition, the possible key cis-elements in response to salt, drought and cold stresses were isolated by the promoter deletion experiment. CONCLUSION: The MzPIP2;1 protein, as a PIP2 aquaporins subgroup member, involved in radial water movement, controls water absorption and usage efficiency and alters transgenic plants drought and salt tolerance. PMID- 26562159 TI - Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small Cell Lung Cancer. AB - IMPORTANCE: Early-phase trials with monoclonal antibodies targeting PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death 1 ligand 1) have demonstrated durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized with respect to either quantity or distribution of expression. OBJECTIVE: To demonstrate PD-L1 protein distribution in NSCLC tumors using both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (QIF) and compare results obtained using 2 different PD-L1 antibodies. DESIGN, SETTING, AND PARTICIPANTS: PD-L1 was measured using E1L3N and SP142, 2 rabbit monoclonal antibodies, in 49 NSCLC whole-tissue sections and a corresponding tissue microarray with the same 49 cases. Non-small cell lung cancer biopsy specimens from 2011 to 2012 were collected retrospectively from the Yale Thoracic Oncology Program Tissue Bank. Human melanoma Mel 624 cells stably transfected with PD-L1 as well as Mel 624 parental cells, and human term placenta whole tissue sections were used as controls and for antibody validation. PD-L1 protein expression in tumor and stroma was assessed using chromogenic IHC and the AQUA (Automated Quantitative Analysis) method of QIF. Tumor-infiltrating lymphocytes (TILs) were scored in hematoxylin eosin slides using current consensus guidelines. The association between PD-L1 protein expression, TILs, and clinicopathological features were determined. MAIN OUTCOMES AND MEASURES: PD-L1 expression discordance or heterogeneity using the diaminobenzidine chromogen and QIF was the main outcome measure selected prior to performing the study. RESULTS: Using chromogenic IHC, both antibodies showed fair to poor concordance. The PD-L1 antibodies showed poor concordance (Cohen kappa range, 0.124-0.340) using conventional chromogenic IHC and showed intra-assay heterogeneity (E1L3N coefficient of variation [CV], 6.75%-75.24%; SP142 CV, 12.17%-109.61%) and significant interassay discordance using QIF (26.6%). Quantitative immunofluorescence showed that PD-L1 expression using both PD-L1 antibodies was heterogeneous. Using QIF, the scores obtained with E1L3N and SP142 for each tumor were significantly different according to nonparametric paired test (P < .001). Assessment of 588 serial section fields of view from whole tissue showed discordant expression at a frequency of 25%. Expression of PD-L1 was correlated with high TILs using both E1L3N (P = .007) and SP142 (P = .02). CONCLUSIONS AND RELEVANCE: Objective determination of PD-L1 protein levels in NSCLC reveals heterogeneity within tumors and prominent interassay variability or discordance. This could be due to different antibody affinities, limited specificity, or distinct target epitopes. Efforts to determine the clinical value of these observations are under way. PMID- 26562160 TI - Structural Insight of a Trimodular Halophilic Cellulase with a Family 46 Carbohydrate-Binding Module. AB - Cellulases are the key enzymes used in the biofuel industry. A typical cellulase contains a catalytic domain connected to a carbohydrate-binding module (CBM) through a flexible linker. Here we report the structure of an atypical trimodular cellulase which harbors a catalytic domain, a CBM46 domain and a rigid CBM_X domain between them. The catalytic domain shows the features of GH5 family, while the CBM46 domain has a sandwich-like structure. The catalytic domain and the CBM46 domain form an extended substrate binding cleft, within which several tryptophan residues are well exposed. Mutagenesis assays indicate that these residues are essential for the enzymatic activities. Gel affinity electrophoresis shows that these tryptophan residues are involved in the polysaccharide substrate binding. Also, electrostatic potential analysis indicates that almost the entire solvent accessible surface of CelB is negatively charged, which is consistent with the halophilic nature of this enzyme. PMID- 26562162 TI - Correction: Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach. PMID- 26562161 TI - Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia. AB - BACKGROUND: ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL) and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients. MATERIALS AND METHODS: Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9) and healthy donors (n = 6). IFN gamma, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay. RESULTS: The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti ROR1 antibodies against CLL cells. ROR1-specific IFN-gamma and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05). CONCLUSION: ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy. PMID- 26562163 TI - O-GlcNAc glycosylation of p27(kip1) promotes astrocyte migration and functional recovery after spinal cord contusion. AB - Glial scar formation derived from astrocyte proliferation and migration influences the functional recovery after spinal cord injury. Cyclin-dependent kinase inhibitor p27(kip1), whose activity is closely related to its phosphorylation state, reportedly regulates astrocyte proliferation and migration. In this study, we reported that p27(Kip1) undergoes O-GlcNAc modification at Ser 2, Ser 110 and Thr 197. Inhibiting O-GlcNAcylation on Ser 2 by gene mutation (S2A) attenuated the phosphorylation of Ser 10, and vice versa. Interestingly, compared with wild type p27(Kip1), S2A p27(Kip1) displayed a decreased interaction with CRM1 and reduced nuclear export following serum starvation and release. In addition, the interaction between stathmin and S2A p27(Kip1) was also decreased. Cytoskeletal proteins microtubules appeared high density in astrocytes transfected with S2A p27(Kip1) especially at the leading edge of the scratch wound. Accordingly, scratch-wound assay revealed that the motility of astrocytes transfected with S2A p27(Kip1) was faster than that of control. Finally, we injected lentiviral vectors immediately after spinal cord contusion, and found the lesion volume of the rat injected with S2A p27(Kip1) was smaller than that of rat injected with wild type p27(Kip1). Besides, the BBB and CBS behavioral tests showed greater functional recovery in S2A p27(Kip1) treated rats. Taken together, our findings revealed a novel function of O-GlcNAc modification of p27(Kip1) in mediating astrocytes migration and functional recovery after spinal cord contusion. PMID- 26562164 TI - Homozygous loss of mouse tetraspanin CD82 enhances integrin alphaIIbbeta3 expression and clot retraction in platelets. AB - Integrin alphaIIbbeta3 is critical for platelet-mediated blood clotting. Tetraspanins are well-established regulators of integrins and genetic loss of tetraspanin CD151 or TSSC6 in mice leads to increased bleeding due to inadequate integrin alphaIIbbeta3 outside-in signaling. Conversely, mild but enhanced integrin alphaIIbbeta3 activation and hyperaggregation is observed in CD9 and CD63 null mice respectively. CD82 is reportedly expressed in platelets; however its function is unknown. Using genetically engineered CD82 null mice, we investigated the role of the tetraspanin CD82 in platelet activation. Loss of CD82 resulted in reduced bleed times in vivo. CD82 was present on the surface of both human and mouse platelets, and its levels did not change upon platelet activation or degranulation. No differences in platelet activation, degranulation, or aggregation in response to ADP or collagen were detected in CD82 null mice. However, the kinetics of clot retraction was enhanced, which was intrinsic to the CD82-null platelets. Integrin alphaIIbbeta3 surface expression was elevated on the platelets from CD82 null mice and they displayed enhanced adhesion and tyrosine kinase signaling on fibrinogen. This is the first report on CD82 function in platelets; which we found intrinsically modulates clot retraction, integrin alphaIIbbeta3 expression, cell adhesion, and tyrosine signaling. PMID- 26562165 TI - Delineating a New Heterothallic Species of Volvox (Volvocaceae, Chlorophyceae) Using New Strains of "Volvox africanus". AB - The volvocine algae represent an excellent model lineage in which to study evolution of female and male genders based on comparative analyses of related species. Among these species, Volvox carteri has been extensively studied as a model of an oogamous and complex organism. However, it may have unique derived features that are not present in other species of Volvox. Therefore, information regarding the characteristics of sexual reproduction of other species of Volvox is also important. In 1971, Starr studied four types of sexuality in several global strains identified as Volvox africanus; however, further taxonomic studies of these strains have been lacking, and strains of three of the four sexual types are not available. Here, we studied the morphology, sexual reproduction, and taxonomy of two V. africanus-like species isolated recently from Lake Biwa, Japan. These two species were very similar to two sexual types described by Starr in 1971: one producing dioecious sexual spheroids in heterothallic strains and the other forming both male spheroids and monoecious spheroids in a single strain. The former species produced zygotes with a reticulate cell wall, whereas a smooth zygote wall was observed in the latter species as in V. africanus previously reported from various localities around the world. Our multigene phylogenetic analysis demonstrated that these are sister species to each other. However, the presence of a compensatory base change in the most conserved region of the secondary structure of nuclear ribosomal DNA internal transcribed spacer 2, hybrid inviability demonstrated by intercrossing experiments, and morphological differences in the density of abutment between the gelatinous material of adjacent cells (individual sheaths) in the spheroid supported the recognition of the two species, V. africanus having a smooth zygote wall and V. reticuliferus Nozaki sp. nov. having a reticulate zygote wall. PMID- 26562167 TI - Effects of Fluoride on the Expression of Beclin1 and mTOR in Ameloblasts. AB - Exposure to high levels of fluoride (F-) can result in dental fluorosis in different individuals, but the mechanism of dental fluorosis remains unclear. Autophagy is a highly conserved intracellular digestion process that degrades damaged organelles and protein aggregates. This study examined the effect of sodium fluoride (NaF) on the expression of Beclin1 and mTOR to elucidate the development mechanisms of dental fluorosis. HAT-7 cells were incubated with various concentrations of NaF, and autophagic vacuoles were studied by transmission electron microscopy. At both mRNA and protein level, expression of Beclin1, which is required for autophagosome formation and decreases the expression of mTOR, an autophagy-related complex, was increased at 1.2 mmol/l NaF compared to baseline (0 mmol/l NaF). Additionally, immunohistochemical analysis was performed on paraffin-embedded rat incisor sections to identify the expression of Beclin1 and mTOR proteins in vitro. Highly significant differences were detected compared to controls. In summary, our results demonstrate unequivocally that excessive amounts of fluoride cause autophagy of HAT-7 cells, indicating that autophagy is involved in dental fluorosis. PMID- 26562166 TI - Genome-Wide Identification of MicroRNAs in Leaves and the Developing Head of Four Durum Genotypes during Water Deficit Stress. AB - MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in plant development and abiotic stress responses. The miRNA transcriptome (miRNAome) under water deficit stress has been investigated in many plant species, but is poorly characterised in durum wheat (Triticum turgidum L. ssp. durum). Water stress during early reproductive stages can result in significant yield loss in durum wheat and this study describes genotypic differences in the miRNAome between water deficit tolerant and sensitive durum genotypes. Small RNA libraries (96 in total) were constructed from flag leaf and developing head tissues of four durum genotypes, with or without water stress to identify differentially abundant miRNAs. Illumina sequencing detected 110 conserved miRNAs and 159 novel candidate miRNA hairpins with 66 conserved miRNAs and five novel miRNA hairpins differentially abundant under water deficit stress. Ten miRNAs (seven conserved, three novel) were validated through qPCR. Several conserved and novel miRNAs showed unambiguous inverted regulatory profiles between the durum genotypes. Several miRNAs also showed differential abundance between two tissue types regardless of treatment. Predicted mRNA targets (130) of four novel durum miRNAs were characterised using Gene Ontology (GO) which revealed functions common to stress responses and plant development. Negative correlation was observed between several target genes and the corresponding miRNA under water stress. For the first time, we present a comprehensive study of the durum miRNAome under water deficit stress. The identification of differentially abundant miRNAs provides molecular evidence that miRNAs are potential determinants of water stress tolerance in durum wheat. GO analysis of predicted targets contributes to the understanding of genotypic physiological responses leading to stress tolerance capacity. Further functional analysis of specific stress responsive miRNAs and their interaction with targets is ongoing and will assist in developing future durum wheat varieties with enhanced water deficit stress tolerance. PMID- 26562168 TI - Visible Versus Near-Infrared Optical Performance of Diffractive Multifocal Intraocular Lenses. AB - PURPOSE: The purpose of this study was to compare the optical performance of diffractive multifocal intraocular lenses (DMIOLs) with visible (VIS) illumination with that of near infrared (NIR) illumination, the latter being used to test pseudophakic eyes in clinical aberrometers and double-pass systems. METHODS: Two DMIOLs of different design (Tecnis +2.75 D ZKB00 and AcrySof +2.5 D SV25T0) were tested in vitro in a model eye under both VIS (lambda = 530 nm) and NIR (lambda = 780 nm) illumination, and variations in the add power of the lenses were determined. Moreover, for the two wavelengths, the energy efficiency and modulation transfer function at the DMIOLs' far and near foci were measured with pupils of 3.0 and 4.5 mm. Two counterpart monofocal IOLs (Tecnis ZA9003 and AcrySof SN60WF) were included as references in the comparison. RESULTS: With VIS light, the two DMIOLs produced relatively well-contrasted images at their near and far foci. Under NIR illumination, the add power increased, whereas the energy efficiency of the near focus decreased and that of far focus increased. Hence, the DMIOLs tended to behave like monofocal lenses because they generated good quality well-contrasted images only at their far foci. CONCLUSIONS: In addition to changes in add power, the optical performances of the DMIOLs measured under either VIS or NIR illumination are considerably different. Whereas they show two distinct (near and far) foci under VIS light, their optical performances under NIR illumination are clearly biased in favor of their far focus. These results may help prevent a misleading use of NIR-based clinical instruments for the assessment of eyes implanted with DMIOLs. PMID- 26562170 TI - Cerenkov Luminescence Imaging for Accurate Placement of Radioactive Plaques in Episcleral Brachytherapy of Intraocular Tumors. AB - PURPOSE: The purpose of this study was to determine the feasibility of using Cerenkov luminescence imaging (CLI) to facilitate plaque placement during episcleral brachytherapy of intraocular tumors. METHODS: Ruthenium-106 (Ru-106) decays to rhodium-106, which in turn emits high-energy beta particles. When the electrons propagate through the eyewall, the so-called Cerenkov effect leads to emission of weak light, which can be captured by high-sensitivity charge-couple device (CCD) cameras. Enucleated porcine eyes were prepared with tumor phantoms made of melanin-containing gelatin. The anterior portion of the globe was removed, and different Ru-106 plaque types (designated CCA, CCB, COB, and CIA) with activities ranging from 6.8 to 16.7 MBq were sutured to the sclera overlying the tumor phantom. The globe was placed in a transparent container with saline. CLI was performed through the anterior opening of the eye using a cooled electron multiplying CCD camera. RESULTS: Exposure times between 5 and 60 seconds produced good quality images of the Cerenkov light. There was a linear relationship between plaque activity and Cerenkov radiance. The perimeters of the CCA and CCB plaques could be seen clearly as circles of light symmetrically surrounding the tumor phantoms. Notched COB and CIA plaques led to images revealing their actual positions in relation to the optic disc and ciliary body, respectively. Simulated plaque tilting resulted in diffuse demarcation of the light. CONCLUSIONS: The study indicates that CLI is a feasible method to ensure accurate placement of Ru 106 plaques in brachytherapy of intraocular tumors. CLI may offer a new tool to improve and document plaque placement, both perioperatively and postoperatively. PMID- 26562169 TI - Corneal Fibroblast Migration Patterns During Intrastromal Wound Healing Correlate With ECM Structure and Alignment. AB - PURPOSE: To assess keratocyte backscattering, alignment, morphology, and connectivity in vivo following a full-thickness corneal injury using the Heidelberg Retina Tomograph Rostock Cornea Module (HRT-RCM), and to correlate these findings with en bloc three-dimensional (3-D) confocal fluorescence and second harmonic generation (SHG) imaging. METHODS: Rabbit corneas were scanned in vivo both before and 3, 7, 14, and 28 days after transcorneal freeze injury (FI), which damages all corneal cell layers. Corneal tissue was also fixed and labeled for f-actin and nuclei en bloc, and imaged using 3-D confocal fluorescence microscopy and SHG imaging. RESULTS: Using the modified HRT-RCM, full-thickness scans of all cell layers were consistently obtained. Following FI, stromal cells repopulating the damaged tissue assumed an elongated fibroblastic morphology, and a significant increase in cellular light scattering was measured. This stromal haze gradually decreased as wound healing progressed. Parallel, interconnected streams of aligned corneal fibroblasts were observed both in vivo (from HRT-RCM reflection images) and ex vivo (from f-actin and nuclear labeling) during wound healing, particularly in the posterior cornea. Second harmonic generation imaging demonstrated that these cells were aligned parallel to the collagen lamellae. CONCLUSIONS: The modified HRT-RCM allows in vivo measurements of sublayer thickness, assessment of cell morphology, alignment and connectivity, and estimation of stromal backscatter during wound healing. In this study, these in vivo observations led to the novel finding that the pattern of corneal fibroblast alignment is highly correlated with lamellar organization, suggesting contact guidance of intrastromal migration that may facilitate more rapid wound repopulation. PMID- 26562171 TI - Estradiol, acting through ERalpha, induces endothelial non-classic renin angiotensin system increasing angiotensin 1-7 production. AB - Intracellular renin-angiotensin system (RAS) can operate independently of the circulating RAS. Estrogens provide protective effects by modulating the RAS. Our aim was to investigate the effect of estradiol (E2) on angiotensin converting enzymes (ACE) 1 and ACE2 expression and activities in human endothelial cells (HUVEC), and the role of estrogen receptors (ER). The results confirmed the presence of active intracellular RAS in HUVEC. Physiological concentrations of E2 induced a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities were also induced with E2. These effects were mediated through ERalpha activation, since ER antagonists ICI 182780 and MPP completely abolished the effect of E2. Moreover, the ERalpha agonist PPT mirrored the E2 effects on ACE1 and ACE2 protein expression and activity. Exposure of endothelial cells to E2 significantly increased Ang-(1-7) production. In conclusion, E2 increases Ang-(1-7) production, through ERalpha, involving increased ACE1 and ACE2 mRNA expression and activity and ACE1 protein levels. PMID- 26562172 TI - Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage. AB - In models of acute brain injury, progesterone improves recovery through several mechanisms including modulation of neuroinflammation. Secondary injury from neuroinflammation is a potential therapeutic target after intracerebral hemorrhage (ICH). For potential translation of progesterone as a clinical acute ICH therapeutic, the present study sought to define efficacy of exogenous progesterone administration in ICH-relevant experimental paradigms. Young and aged C57BL/6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.05-0.075 U) or autologous whole blood (35 MUl) injection. Progesterone at varying doses (4-16 mg/kg) was administered at 2, 5, 24, 48, and 72 h after injury. Rotarod and Morris water maze latencies were measured on days 1-7 and days 28-31 after injury, respectively. Hematoma volume, brain water content (cerebral edema), complementary immunohistochemistry, multiplex cytokine arrays, and inflammatory proteins were assessed at prespecified time points after injury. Progesterone (4 mg/kg) administration improved rotarod and water maze latencies (p < 0.01), and decreased cerebral edema (p < 0.05), microglial proliferation, and neuronal loss (p < 0.01) in young and aged male, young OVX, and aged female mice. Brain concentration of proinflammatory cytokines and Toll-like receptor-associated proteins were also decreased after progesterone (4 mg/kg) treatment (p < 0.01). Progesterone-treated young female mice showed no detectable effects. Exogenous progesterone improved short- and long-term neurobehavioral recovery and modulated neuroinflammation in male and OVX mice after ICH. Future studies should validate these findings, and address timing and length of administration before translation to clinical trial. PMID- 26562173 TI - HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda. AB - BACKGROUND: Studies of patients failing second-line antiretroviral therapy (ART) in resource-limited settings (RLS) are few. Evidence suggests most patients who appear to be virologically failing do so not due to drug resistance but to poor adherence, which, if properly addressed, could allow continued use of less expensive first- and second-line regimens. Drug resistant mutations (DRMs) were characterized among patients virologically failing second-line ART in Rwanda. METHODS: A total of 128 adult patients receiving second-line ART for at least 6 months were invited to participate; 74 agreed and had HIV-1 viral load (VL) measured. Resistance genotypes were conducted in patients with virological failure (VF; that is, VL >=1,000 copies/ml). RESULTS: In total, 35 patients met the criteria for VF. The median time on lopinavir/ritonavir-based second-line ART was 2.7 years. Of 30 successful resistance genotype analyses, 13 (43%) had >=1 nucleoside reverse transcriptase inhibitor (NRTI) mutation, 18 (60%) had at least 1 non-NRTI mutation and 5 (17%) had at least 1 major protease inhibitor mutation. Eleven (37%) had virus without significant mutations that would be fully sensitive to first-line ART; 12 (40%) had DRM to first-line ART but sensitive to second-line ART. Only 7 patients (23%) demonstrated a DRM profile requiring third line ART. CONCLUSIONS: Among 30 genotyped samples of patients with VF on second line ART, more than one-third had no significant DRMs, implicating poor adherence as the primary cause of VF. The majority of patients (77%) would not have required third-line ART. These findings reinforce the need for intensive adherence assessment and counselling for patients who appear to be failing second line ART in RLS. PMID- 26562174 TI - Effects of Space Environment on Genome, Transcriptome, and Proteome of Klebsiella pneumoniae. AB - BACKGROUND AND AIMS: The aim of this study was to explore the effects of space flight on Klebsiella pneumoniae. METHODS: A strain of K. pneumoniae was sent to space for 398 h aboard the ShenZhou VIII spacecraft during November 1, 2011 November 17, 2011. At the same time, a ground simulation with similar temperature conditions during the space flight was performed as a control. After the space mission, the flight and control strains were analyzed using phenotypic, genomic, transcriptomic and proteomic techniques. RESULTS: The flight strains LCT-KP289 exhibited a higher cotrimoxazole resistance level and changes in metabolism relative to the ground control strain LCT-KP214. After the space flight, 73 SNPs and a plasmid copy number variation were identified in the flight strain. Based on the transcriptomic analysis, there are 232 upregulated and 1879 downregulated genes, of which almost all were for metabolism. Proteomic analysis revealed that there were 57 upregulated and 125 downregulated proteins. These differentially expressed proteins had several functions that included energy production and conversion, carbohydrate transport and metabolism, translation, ribosomal structure and biogenesis, posttranslational modification, protein turnover, and chaperone functions. At a systems biology level, the ytfG gene had a synonymous mutation that resulted in significantly downregulated expression at both transcriptomic and proteomic levels. CONCLUSIONS: The mutation of the ytfG gene may influence fructose and mannose metabolic processes of K. pneumoniae during space flight, which may be beneficial to the field of space microbiology, providing potential therapeutic strategies to combat or prevent infection in astronauts. PMID- 26562175 TI - Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria. AB - BACKGROUND AND AIMS: Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. METHODS: The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. RESULTS: Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. CONCLUSION: Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. PMID- 26562177 TI - Quantification of X. laevis vitellogenin by liquid chromatography tandem mass spectrometry. AB - Over the last several decades, there has been an increase in public awareness and regulatory activity in regard to the presence of emerging contaminants in the environment that may have the potential to interact with the endocrine system of exposed wildlife. Alterations in vitellogenin (VTG), a high density yolk precursor protein, can indicate endocrine activity in oviparous species, including many fish and amphibians. While various methodologies and experiments have been performed to characterize baseline VTG concentrations among commonly studied fish species, fewer methodologies for accurately quantifying amphibian VTG are available. Since there is relatively little information available on background VTG levels in male and female frogs, the present investigation set out to quantify baseline levels of VTG in juvenile as well as adult male and female African clawed frogs (Xenopus laevis) using a newly developed liquid chromatography tandem mass spectrometry method. This new methodology for quantifying VTG in X. laevis frog blood plasma can be applied in mechanistic and toxicity studies with X. laevis to better characterize potential endocrine modes of action. PMID- 26562176 TI - Assessing Deep Retinal Capillary Ischemia in Paracentral Acute Middle Maculopathy by Optical Coherence Tomography Angiography. AB - PURPOSE: To assess microvascular blood flow of the deep retinal capillary plexus in eyes with paracentral acute middle maculopathy using optical coherence tomography (OCT) angiography. DESIGN: Retrospective, multicenter observational case series. METHODS: Clinical and multimodal imaging findings from 8 patients with paracentral acute middle maculopathy were reviewed and analyzed. OCT angiography scans were analyzed and processed, and vessel density was calculated. RESULTS: Eight patients (7 male, 1 female, aged 9-82 years) were included. OCT angiography was obtained at either the acute (4 cases) or old stage (4 cases). Scans of the deep capillary plexus showed preservation of perfusion in acute lesions and capillary attenuation in old cases. Cases of central retinal artery occlusion showed marked loss of the deep capillary plexus. The mean vessel density of the superficial capillary plexus in normal fellow eyes was 12.8 +/- 1.8 mm(-1) vs 12.1 +/- 1.9 mm(-1) in eyes with paracentral acute middle maculopathy (reduction -6.0%, P = .08). The mean vessel density of the deep capillary plexus in normal fellow eyes was 17.5 +/- 1.4 mm(-1) vs 14.7 +/- 3.5 mm(-1) in eyes with paracentral acute middle maculopathy (reduction -19.4%, P = .04). This significant difference was representative of the eyes with old lesions. CONCLUSION: Paracentral acute middle maculopathy lesions correspond to preservation of perfusion in focal acute lesions and to pruning of the plexus in old cases. Cases of central retinal artery occlusion demonstrate marked hypoperfusion of the deep capillary plexus. Our study further supports an ischemic pathogenesis of this retinal vasculopathy. PMID- 26562178 TI - Inhibition of BCL-2 leads to increased apoptosis and delayed neuronal differentiation in human ReNcell VM cells in vitro. AB - BCL-2 is a multifunctional protein involved in the regulation of apoptosis, cell cycle progression and neural developmental processes. Its function in the latter process is not well understood and needs further elucidation. Therefore, we characterized the protein expression kinetics of BCL-2 and associated regulatory proteins of the intrinsic apoptosis pathway during the process of neuronal differentiation in ReNcell VM cells with and without functional inhibition of BCL 2 by its competitive ligand HA14-1. Inhibition of BCL-2 caused a diminished BCL-2 expression and higher levels of cleaved BAX, activated Caspase-3 and cleaved PARP, all pro-apoptotic markers, when compared with untreated differentiating cells. In parallel, flow cytometric analysis of HA14-1-treated cells revealed a delayed differentiation into HuC/D+ neuronal cells when compared to untreated differentiating cells. In conclusion, BCL-2 possess a protective function in fully differentiated ReNcell VM cells. We propose that the pro-survival signaling of BCL-2 is closely connected with its stimulatory effects on neurogenesis of human neural progenitor cells. PMID- 26562179 TI - Early development of the fetal central sulcus on 7.0T magnetic resonance imaging. AB - In the previous studies, the criterion for deciding the occurrence time of the fetal central sulcus (CS) on magnetic resonance imaging (MRI) is based on the observation by the eyes. There have been no existing quantitative standards or numerical criteria in this field. In this study, we reconstructed the three dimension (3D) images of the fetal brain based on the 7.0T MR images of 45 Chinese fetal specimens from the 11 to 22 weeks of gestational age (GA). Then we obtained data by measuring the maximum depth and length of the CS so as to analyze the early developmental pattern of it. These measures, especially CS depth, can be used to quantitatively determine the time of emergence of the fetal CS during the development. Statistics show that there are no gender or interhemispheric asymmetries of the CS from GA of 11 to 22 weeks. PMID- 26562180 TI - Simultaneous determination of mebeverine hydrochloride and chlordiazepoxide in their binary mixture using novel univariate spectrophotometric methods via different manipulation pathways. AB - Smart, sensitive, simple and accurate spectrophotometric methods were developed and validated for the quantitative determination of a binary mixture of mebeverine hydrochloride (MVH) and chlordiazepoxide (CDZ) without prior separation steps via different manipulating pathways. These pathways were applied either on zero order absorption spectra namely, absorbance subtraction (AS) or based on the recovered zero order absorption spectra via a decoding technique namely, derivative transformation (DT) or via ratio spectra namely, ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), spectrum subtraction (SS), constant multiplication (CM) and constant value (CV) methods. The manipulation steps applied on the ratio spectra are namely, ratio difference (RD) and amplitude modulation (AM) methods or applying a derivative to these ratio spectra namely, derivative ratio (DD(1)) or second derivative (D(2)). Finally, the pathway based on the ratio spectra of derivative spectra is namely, derivative subtraction (DS). The specificity of the developed methods was investigated by analyzing the laboratory mixtures and was successfully applied for their combined dosage form. The proposed methods were validated according to ICH guidelines. These methods exhibited linearity in the range of 2-28MUg/mL for mebeverine hydrochloride and 1-12MUg/mL for chlordiazepoxide. The obtained results were statistically compared with those of the official methods using Student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision. PMID- 26562181 TI - Structural characterization, thermoluminescence studies and kinetic parameters of SrSO4:Eu nanophosphors under X-ray and gamma excitations. AB - Nanostructured SrSO4:Eu phosphors with high thermoluminescence (TL) emission temperatures have been synthesized through a controlled chemical precipitation method. Structural analysis and TL studies under both gamma-ray and X-ray excitations were done. The phosphors were characterized using Powder X-ray diffraction, X-ray photoelectron spectroscopy, SEM, TEM, thermogravimetry, UV-VIS and photoluminescence studies. The average crystallite size estimated using PXRD data is found to be around 40nm. XPS and PL studies reveal that Eu(2+) ions are the luminescence emission centres in the phosphor. The phosphor is found to be highly TL sensitive to both gamma-rays and X-rays with very high emission temperature which is not reported so far. The emission behaviour is suitable for environmental radiation dosimetry applications. The TL glow curve shows well defined isolated high temperature emission peak at 312 degrees C under 2Gy gamma excitation and 284 degrees C for low energy diagnostic X-ray irradiation and 271 degrees C for high energy therapeutic X-rays. Chen's peak shape method is applied to obtain the kinetic parameters behind the TL emission. The TL mechanism is found to follow second order kinetics, suggesting the probability of re-trapping of charge carriers. PMID- 26562182 TI - Mastering analytical challenges for the characterization of pentacyclic triterpene mono- and diesters of Calendula officinalis flowers by non-aqueous C30 HPLC and hyphenation with APCI-QTOF-MS. AB - Pentacyclic triterpene mono- and diesters have been isolated from Calendula officinalis flowers. GC-MS, APCI-Exactive Orbitrap HR-MS and NMR allowed to identify the triterpene skeleton in various samples (different triterpene mixtures from Calendula n-hexane extract). NMR provided evidence that triterpene diesters are present in the samples as well. However, the corresponding quasi molecular ions could not be detected by APCI-Exactive Orbitrap HR-MS. Instability of triterpene diesters and loss of a fatty acid residue, respectively, in the ion source made their MS detection challenging. Thus, a set of new APCI-QTOF-MS methods (using the TripleTOF 5600+ mass spectrometer) were developed which made it eventually possible to solve this problem and confirm the diester structures by MS via quasi-molecular ion [M+H](+) detection. Direct infusion APCI-QTOF MS experiments in MS/MS high sensitivity scan mode with low collision energy and multi-channel averaging acquisition (MCA) allowed the detection of quasi molecular ions of triterpene diesters for the first time and unequivocally confirmed the presence of faradiol 3,16-dimyristate and -dipalmitate, as well as the corresponding mixed diesters faradiol 3-myristate,16-palmitate and faradiol 3 palmitate,16-myristate. Preferential loss of the fatty acid in 16-position made it possible to distinguish the mixed diesters by MS/MS spectra. Their chromatographic separations turned out to be challenging due to their bulkiness and extended molecular dimensions. However, separation could be achieved by an uncommon non-aqueous RPLC mode with an in-house synthesized C30 phase. Finally, two (U)HPLC-APCI-QTOF-MS methods with C18- and C30-based non-aqueous RPLC provided suitable, sensitive assays to monitor the presence of monoesters and diesters of various triterpenes (faradiol, maniladiol, arnidiol, arnitriol A and lupane-3beta,16beta,20-triol esters) in the n-hexane extract of C. officinalis with high mass resolution and good mass accuracy. PMID- 26562183 TI - Analysis of PVC plasticizers in medical devices and infused solutions by GC-MS. AB - In 2008, di-(2-ethylhexyl) phthalate (DEHP), was categorized as CMR 1B under the CLP regulations and its use in PVC medical devices (MD) was called into question by the European authorities. This resulted in the commercialization of PVC MDs plasticized with the DEHP alternative plasticizers tri-octyl trimellitate (TOTM), di-(2-ethylhexyl) terephthalate (DEHT), di-isononyl cyclohexane-1,2-dicarboxylate (DINCH), di-isononyl phthalate (DINP), di-(2-ethylhexy) adipate (DEHA), and Acetyl tri-n-butyl citrate (ATBC). The data available on the migration of these plasticizers from the MDs are too limited to ensure their safe use. We therefore developed a versatile GC-MS method to identify and quantify both these newly used plasticizers and DEHP in MDs and to assess their migration abilities in simulant solution. The use of cubic calibration curves and the optimization of the analytical method by an experimental plan allowed us to lower the limit of plasticizer quantification. It also allowed wide calibration curves to be established that were adapted to this quantification in MDs during migration tests, irrespective of the amount present, and while maintaining good precision and accuracy. We then tested the developed method on 32 PVC MDs used in our hospital and evaluated the plasticizer release from a PVC MD into a simulant solution during a 24h migration test. The results showed a predominance of TOTM in PVC MDs accompanied by DEHP (<0.1% w/w), DEHT, and sometimes DEHA. The migration tests showed a difference in the migration ability between the plasticizers and a non-linear kinetic release. PMID- 26562184 TI - Toxicity of nickel in the marine calanoid copepod Acartia tonsa: Nickel chloride versus nanoparticles. AB - Nickel compounds are widely used in industries and have been massively introduced in the environment in different chemical forms. Here we report the effect of two different chemical forms of nickel, NiCl2 and nickel nanoparticles (NiNPs), on the reproduction of the marine calanoid copepod Acartia tonsa. The behavior of nickel nanoparticles was analyzed with different techniques and with two protocols. In the "sonicated experiment" (SON) NiNP solution was sonicated while in the "non-sonicated experiment" (NON-SON) the solution was vigorously shaken by hand. Final nominal concentrations of 5, 10 and 50mgL(-1) and 1, 5 and 10mgL(-1) NiNPs were used for the acute and semichronic tests, respectively. Nanoparticle size did not change over time except for the highest concentration of 50mgL(-1) NiNPs, in which the diameter increased up to 843nm after 48h. The concentration of Ni dissolved in the water increased with NP concentration and was similar for SON and NON-SON solutions. Our results indicate that sonication does not modify toxicity for the copepod A. tonsa. Mean EC50 values were similar for NON-SON (20.2mgL(-1)) and SON experiments (22.14mgL(-1)) in the acute test. Similarly, no differences occurred between the two different protocols in the semichronic test, with an EC50 of 7.45mgL(-1) and 6.97mgL(-1) for NON-SON and SON experiments, respectively. Acute and semichronic tests, conducted exposing A. tonsa embryos to NiCl2 concentrations from 0.025 to 0.63mgL(-1), showed EC50 of 0.164 and 0.039mgL(-1), respectively. Overall, A. tonsa is more sensitive to NiCl2 than NiNPs with EC50 being one order of magnitude higher for NiNPs. Finally, we exposed adult copepods for 4 days to NiCl2 and NiNPs (chronic exposure) to study the effect on fecundity in terms of daily egg production and naupliar viability. Egg production is not affected by either form of nickel, whereas egg viability is significantly reduced by 0.025mgL(-1) NiCl2 and by 8.5mgL(-1) NiNPs. At NiNP concentration below the acute EC50 (17mgL(-1)) only 9% of embryos hatched after 4 days. Interestingly, the percentage of naupliar mortality (>82%) observed in the semichronic test at the nominal concentration of 10mgL(-1) NiNPs corresponding to almost 0.10mgL(-1) of dissolved Ni, was similar to that recorded at the same Ni salt concentration. Electron microscopical analyses revealed that A. tonsa adults ingest NiNPs and excrete them through fecal pellets. To the best of our knowledge, this is the first study investigating the toxicity of two different forms of Ni on the reproductive physiology of the copepod A. tonsa and showing the ability of the calanoid copepod to ingest nanoparticles from seawater. PMID- 26562185 TI - PDE4D phosphorylation: A coincidence detector integrating multiple signaling pathways. AB - In Eukaryotes, more than 100 different phosphodiesterase (PDE) proteins serve to fine-tune cyclic nucleotide (cAMP and cGMP) signals and contribute to specificity of signaling. In mammals, PDEs are divided into 11 families, of which PDE4 represents the largest family. Four genes (pde4a, pde4b, pde4c and pde4d) encode for this class of enzymes in mammals and give rise to more than 20 variants. Within this family of genes, PDE4D was discovered on the basis of its regulatory properties and its induction by hormones and cAMP. PDE4D has often been used as the prototype PDE4 and large body of work has been generated on the biochemical, pharmacological, and physiological properties of this enzyme. This review covers the regulation of PDE4D by phosphorylation, the impact of this regulation in the context of the structure of this protein, and the functional consequences of this complex pattern of posttranslational modifications. PMID- 26562186 TI - Effects of a viscous-fibre supplemented evening meal and the following un supplemented breakfast on post-prandial satiety responses in healthy women. AB - The post-prandial satiety response and "second-meal effect" of a viscous fibre supplement PolyGlycopleX((r)) (PGX((r))) was evaluated in a single-blind, randomised controlled crossover study of 14 healthy adult women. The two hour post-prandial satiety response, expressed as the area under the curve (AUC) of perceived hunger/fullness score versus post-prandial time, of a standardised evening meal with concurrent intake of either PGX softgel or rice flour softgel (control) was determined. On the following morning, after an overnight fast, the four hour satiety response to a standardised breakfast with no softgel supplementation was assessed. A significantly higher satiety response (AUC) to the standard dinner for the PGX-supplemented dinner compared with the control dinner (p=0.001) was found. No significant difference (p=0.09) was observed in the satiety response (AUC) of the breakfast regardless of which supplemented dinner had been consumed prior, however the p value indicated a trend towards a higher response to the breakfast following the PGX-supplemented dinner. The fullness scores of the breakfast following the PGX-supplemented dinner at 15, 30, 90, 120, 150, 180, 210 and 240min post-prandial were significantly higher than those for the breakfast following the control dinner (p=<0.001, 0.007, 0.009, 0.009, 0.049, 0.03, 0.003 and <0.001 respectively). PGX supplementation at dinner increased the satiety effects of both the dinner itself and the subsequent un supplemented breakfast; a "second meal effect" indicting the potential for this fibre supplement to induce extended satiety. PMID- 26562187 TI - The Leeds food preference questionnaire after mild sleep restriction - A small feasibility study. AB - Besides the increased sedentary lifestyle and increased caloric intake, changes in dietary composition may play an important role in the increased prevalence of obesity. Because inadequate sleep could be a risk factor in the aetiology of obesity, reliable methods for assessing food intake and food choice after sleep restriction are needed. We translated the Leeds food preference questionnaire (LFPQ), addressing preferences for sweet/savoury tastes and low-fat/high-fat foods, into Dutch, and tested it in 15 mildly sleep-restricted psychology students. The participants completed the LFPQ in our laboratory on two separate occasions, with approximately one week in between. Sleep on the preceding night was not controlled, but mild sleep-restriction was confirmed by a short sleep latency test (sSLT) or a short maintenance of wakefulness test (sMWT). Each participant completed the sSLT and sMWT once, just before the LFPQ, in a cross over design randomised for the first test. Differences were present in preferences for food items from different categories (sweet/savoury and low fat/high-fat; p<0.001). The choice frequencies for various food categories were comparable on both occasions (p=0.27). The choice frequencies for individual items were also comparable on both occasions (p=0.27). The LFPQ is easily implemented under mild sleep-restricted conditions, and translation is straightforward. Future studies using the LFPQ after sleep restriction could elucidate if restricting sleep or longer periods affects food choice, which could underlie increases in obesity risk. PMID- 26562188 TI - A facile and effective immobilization of glucose oxidase on tannic acid modified CoFe2O4 magnetic nanoparticles. AB - This article presents a study of glucose oxidase (GOx) immobilization by employing tannic acid (TA) modified-CoFe2O4 (CFO) magnetic nanoparticles which demonstrates novel aspect for enzyme immobilization. By using the strong protein and tannic acid binding, GOx immobilization was carried out via physical adsorption in a simpler way compared with the other immobilization methods which require various chemicals and complicated procedures which is difficult, expensive, time-consuming, and destructive to the enzyme structure. CFO was synthesized by hydrothermal synthesis and modified with TA to immobilize GOx. The immobilized GOx demonstrated maximum catalytic activity at pH 6.5 and 45 degrees C. The samples were characterized by vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), zeta potential, and fourier transform infrared spectroscopy (FTIR), all of which confirm the surface modification of CFO and GOx immobilization. Also, field emission scanning electron microscope (FESEM) and X ray diffraction (XRD) were performed to demonstrate the surface morphology and chemical structure of samples. According to the Lineweaver-Burk plot, GOx possessed lower affinity to glucose after immobilization, and the Michelis-Menten constant (KM) of immobilized and free GOx were found to be 50.05 mM and 28.00 mM, respectively. The immobilized GOx showed excellent reusability, and even after 8 consecutive activity assay runs, the immobilized GOx maintained ca. 60% of its initial activity. PMID- 26562189 TI - Effect of silica nanoparticles on the interfacial properties of a canonical lipid mixture. AB - The incorporation of silica nanoparticles (NPs) from the subphase into Langmuir lipid monolayers formed by three components, 1,2-Dipalmitoyl-sn-glycerol-3 phosphocholine (DPPC), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and Cholesterol (Chol), modifies the thermodynamic and rheological behavior, as well as the structure of the pristine lipid film. Thus, the combination of structural characterization techniques, such as Brewster Angle Microscopy (BAM) and Atomic Force Microscopy (AFM), with interfacial thermodynamic and dilational rheology studies has allowed us to deepen on the physico-chemical bases governing the interaction between lipid molecules and NPs. The penetration of NPs driven by the interaction (electrostatic or hydrogen bonds) with the polar groups of the lipid molecules affects the phase behaviour (surface pressure-area, P-A , isotherm) of the monolayer. This can be easily rationalized considering the modification of the packing and cohesion of the molecules at the interface as revealed BAM and AFM images. Furthermore, oscillatory barrier experiments have allowed obtaining information related to the effect of NPs on the monolayer response under dynamic conditions that presents a critical impact on the characterization of biological relevant systems because most of the processes of interest for these systems present a dynamic character. PMID- 26562190 TI - Cationic nanogels as Trojan carriers for disruption of endosomes. AB - The comparison study of interaction of linear poly(2-dimethyl amino)ethyl methacrylate and its cationic nanogels of various cross-linking with both DNA and sodium poly(styrene sulfonate) has been performed. Although all amino groups of the nanogels proved to be susceptible for protonation, their accessibility for ion pairing with the polyanions was controlled and impaired with the cross linking. The investigation of nanogels complexes with cells in culture that was accomplished by using of calcein pH-sensitive probe revealed a successive increase in the cytoplasmic fluorescence upon the growth in the cross-linking due to calceine leakage from acidic compartments to cytosol. This regularity implies that amino groups which are buried presumably inside the nanogel are protected against the ion-pairing with polyanions of plasma membrane and hence are able to manifest buffer properties while captured into acidic endosomes, i.e. possess lyso/endosomolytic capacity. These findings suggest that network architecture makes an important contribution to proton sponge properties of weak polycations. PMID- 26562191 TI - Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels. AB - Many drugs are unable to breach the blood-brain barrier (BBB). Protein-directed transport of nanomedicine by receptor-mediated transcytosis (RMT) has been investigated as a means to overcome this problem. In this study, we screened transporters using an in vitro transcytosis assay system in rat serum to identify candidates that could guide nanoparticles through the BBB by RMT. The proteins that showed over 5-fold decreases in RMT when treated with chloropromazine, an inhibitor of clathrin-dependent endocytosis, were selected and identified by Maldi-TOF mass spectroscopy. Eleven proteins, including transthyretin (Ttr), and creatine kinase-muscle type (CKM), were identified as being capable of penetrating the endothelial cell layer by RMT. Among them, 10 proteins have not yet been used to transport nanomaterials across the BBB. To validate their activity as nanoparticle transporters in vivo, Ttr and CKM were conjugated to the surface of quantum dot (QD) nanoparticles and administrated intravenously. After 8h, the distribution of Ttr-QDs and CKM-QDs in brain tissue was analyzed. The results showed transcytosis of Ttr-QD conjugates across the BBB in rats as well as in in vitro assays, which was in contrast to the results observed for bare QDs and CKM-QDs. Taken together, these results indicate that Ttr is a new putative transporter for nanomedicines across the BBB. PMID- 26562192 TI - Phospholipid/cholesterol/decanethiol mixtures for direct assembly of immunosensing interfaces. AB - In this work, a simple yet robust method to prepare lipid-based biosensing interfaces on gold using common lipids (a phospholipid and cholesterol) and an alkanethiol is reported. The lipids were carefully chosen to tailor the biophysical properties of the bilayer. The simplicity of the method relies on the incorporation of a small percentage of decanethiol in the lipid vesicles for a direct formation of a thiol-linked supported lipid bilayer, which is advantageous in several respects. It prevents the use of specially synthesized thiolipids and preserves the natural fluidity and dynamics of the lipids. As a consequence the whole arrangement is extremely stable regarding ionic strength changes and solution flow during surface plasmon resonance experiments. Moreover, we show that this interface is very effective on suppressing the nonspecific adsorption of proteins on the surface, and enables the covalent attachment of the recognition antibody. The subsequent detection of specific interaction toward antigen was monitored in real-time by SPR and confirmed by ellipsometric measurements. This lipid-based biosensing platform is versatile and can be adapted to the biorecognition reaction of interest. PMID- 26562193 TI - The impact of detoxifying and repair gene polymorphisms and the levels of serum ROS in the susceptibility to multiple sclerosis. AB - OBJECTIVE: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease with unknown etiology. Oxidative stress (OS) has been implicated to play a role in its cause; therefore, antioxidants and repair systems may help in restoring oxidant-antioxidant balance. Since polymorphisms in DNA repair genes can result in reduced DNA repair capacity, it is important to investigate its association with OS products to demonstrate the impact of individual susceptibility. Our aim is to examine whether a defect in one of the detoxifying and DNA repair enzyme systems could explain the association between MS and exposure to OS products. METHODS: We investigated the association of polymorphisms in the metabolizing and DNA repair genes with serum Reactive Oxygen Species (ROS) levels. Gene polymorphisms were analyzed by simultaneous multiplex and Restriction Fragment Length Polymorphism Polymerase Chain Reaction and serum ROS levels were detected. RESULTS: OGG1 Ser/Cys and Ser/Cys+Cys/Cys genotypes had higher MS risk. XRCC1 Arg/Gln+Gln/Gln genotype increased the risk of MS. CONCLUSIONS: Our data suggested that OGG1 Ser326Cys gene polymorphism is a major genetic factor involved in the development of MS. Smoking is also a pivotal confounding factor for subjects with mutant genotypes of XRCC1 Arg399Gln. Further studies are needed to reaffirm our results. PMID- 26562194 TI - Sagittal alignment of the spine: What do you need to know? AB - Sagittal alignment, often misrepresented as sagittal balance, describes the ideal and "normal" alignment in the sagittal plane, resulting from the interplay between various organic factors. Any pathology that alters this equilibrium instigates sagittal malalignment and its compensatory mechanisms. As a result, sagittal malalignment is not limited to adult spinal deformity; its pervasiveness extends through most spinal disorders. While further research is developing, the literature reports clinically relevant radiographic parameters that have significant relationships with patient-reported outcomes. This article aims to provide a pragmatic review of sagittal plane analysis. At the end of this review, the reader should be able to analyze the sagittal plane of the spine, identify compensatory mechanisms, and choose patient-specific alignment targets. PMID- 26562195 TI - Risk factors for meningitis after craniotomy in patients with subarachnoid hemorrhage due to anterior circulation aneurysms rupture. AB - OBJECTIVES: Postoperative meningitis is a serious complication occurring after neurosurgical interventions. However, few investigations have focused specifically on the risk factors that predispose patients to meningitis after major craniotomy. This study identified the risk factors for postoperative meningitis after neurovascular surgery, and investigated the relationship between postoperative meningitis and clinical outcome. PATIENTS AND METHODS: A total of 148 consecutive patients with subarachnoid hemorrhage (SAH) who underwent clipping surgery through a pterional approach within 72 h between January 2007 and September 2011 were retrospectively analyzed. The treatment strategy of our hospital for patients with SAH was based on the findings of digital subtraction angiography in the acute phase. Coil embolization was firstly considered, and clipping through craniotomy if indicated was performed as soon as possible. Prophylactic antibiotics were administered before beginning craniotomy and for at least 3 days after. Hydrocortisone was used to prevent hyponatremia if allowed by the medical condition of the patient. Intrathecal administration of nicardipine hydrochloride was given if required for vasospasm treatment. Meningitis was clinically diagnosed from the blood samplings and cerebrospinal fluid (CSF) examinations. Data were collected from the electronic and paper charts. The status of modified Rankin scale (mRS) 0-2 at discharge was defined as favorable outcome. RESULTS: A total of 14 patients (9.5%) had meningitis during this study period. Symptomatic vasospasm was detected in 33 patients (22.3%), and 12 patients (8.1%) had permanent neurological deficits caused by vasospasm. Overall, 109 patients (73.6%) had favorable outcome. The longer duration of drainage placement, presence of CSF leakage, and intrathecal administration of vasodilatory agent showed significantly higher incidence of postoperative meningitis in univariate analysis (p=0.0093, 0.0017, and 0.0090, respectively). The proportion of favorable outcome patients at discharge (mRS 0-2) was significantly lower in patients with postoperative meningitis (35.7%) than in patients without it (77.6%) (p=0.0004). The duration of in-hospital stay was significantly longer in patients with postoperative meningitis (median 58.5, range 28-115 days) than in patients without it (median 38.5, range 19-149 days) (p<0.001). Multivariate logistic regression analysis showed that only presence of CSF leakage was associated with postoperative meningitis (p=0.0299). CONCLUSION: Meningitis after surgery is still a serious complication that requires preventative intervention. The clinical outcome of patients with postoperative meningitis after neurovascular surgery is not still satisfactory. PMID- 26562196 TI - The use of off-labeled drugs in wound healing: oxandrolone. PMID- 26562198 TI - Association news: alliance of wound care stakeholders. PMID- 26562199 TI - Do you know how to read and properly interpret the National Correct Coding Initiative Edits? PMID- 26562200 TI - Proxy study on minimizing risk of sacral pressure ulcers while complying with ventilator-associated pneumonia risk reduction guidelines. AB - Bed positioning poses a subtle, yet important, tradeoff in the competing needs of hospitalized patients, particularly those susceptible to lower respiratory tract infections and/or pressure ulcers. Although it is widely held that a minimum 30 degrees incline is necessary to mitigate risk of ventilator-acquired pneumonia, it is unclear what effect semirecumbent positioning has on the risk of pressure ulcerations. The authors test several hypotheses with the objective of elucidating the relationship between bed incline, posture, and incline, pursuant to a more evidence-based recommendation for practice in clinical care. To this end, interfacial pressures from 40 healthy subjects were analyzed following observation in both supine and sidelying positions, at shallow (30 degrees ) and moderate (45 degrees ) bed-angle incline. Summarily, the authors report that supine postures reduce pressure signatures associated with pressure ulceration versus sidelying position: 15% increase area of contact (P = 1.3*10), and 17% decrease in ratio of peak to average pressure (P = 3.1*10). Within supine posture, the authors found significant increases in 4 measures of local pressure, including average pressure (10.4% decrease, P = .005) and coefficient of pressure variation (22.1%, P = 2.2*10) at moderate incline. The authors conclude that supine bed positionings at moderate incline appear to reduce predictors of pressure ulceration. PMID- 26562201 TI - Evaluation of commonly used temporary skin dressings and a newly developed collagen matrix for treatment of superficial wounds. AB - OBJECTIVE: In the authors' experience, extended superficial-thickness wounds often were treated with the application of synthetic temporary wound dressings. There is a broad range of expensive products available in this market. The aim of this study was to compare commonly used temporary skin dressings with a newly developed collagen matrix. METHODS: A total of 56 standardized superficial skin defects were generated on the back of 28 adult male Lewis rats using a skin dermatome. The wounds were treated with Biobrane (Smith & Nephew, St Petersburg, Florida) (n = 14), Suprathel (PolyMedics, Denkendorf, Germany) (n = 14), and newly developed Collagen Cell Carrier (Naturin Viscofan, Weinheim, Germany) (CCC; n = 14). Histological evaluation was performed at 3 months' postoperative in regard to quality of newly formed skin. RESULTS: In regard to epidermal cell count and thickness of skin, Biobrane and Suprathel demonstrated comparable values, whereas CCC demonstrated higher epidermal cell count and thicker neoepidermis. The epidermal thickness of CCC was comparable to untreated, healthy skin. CONCLUSIONS: The presented results reveal the potential of CCC in the treatment of superficial skin defects and encourages further evaluation of CCC in surgical applications and regenerative medicine. PMID- 26562202 TI - Celebrating 30 years of the Clinical Symposium on Advances in Skin & Wound Care. PMID- 26562203 TI - A predictive model for pressure ulcer outcome: the Wound Healing Index. AB - PURPOSE: The purpose of this learning activity is to provide information regarding the creation of a risk-stratification system to predict the likelihood of the healing of body and heel pressure ulcers (PrUs). TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Explain the need for a PrU risk stratification tool.2. Describe the purpose and methodology of the study.3. Delineate the results of the study and development of the Wound Healing Index. ABSTRACT: OBJECTIVE: : To create a validated system to predict the healing likelihood of patients with body and heel pressure ulcers (PrUs), incorporating only patient- and wound-specific variables. DESIGN: The US Wound Registry data were examined retrospectively and assigned a clear outcome (healed, amputated, and so on). Significant variables were identified with bivariate analyses. Multivariable logistic regression models were created based on significant factors (P < .05) and tested on a 10% randomly selected hold-out sample. SETTING: Fifty-six wound clinics in 24 states PATIENTS: : A total of 7973 body PrUs and 2350 heel PrUs were eligible for analysis. INTERVENTION: Not applicable MAIN OUTCOME MEASURE: : Healed PrU MAIN RESULTS:: Because of missing data elements, the logistic regression development model included 6640 body PrUs, of which 4300 healed (64.8%), and the 10% validation sample included 709 PrUs, of which 477 healed (67.3%). For heel PrUs, the logistic regression development model included 1909 heel PrUs, of which 1240 healed (65.0%), and the 10% validation sample included 203 PrUs, of which 133 healed (65.5%). Variables significantly predicting healing were PrU size, PrU age, number of concurrent wounds of any etiology, PrU Stage III or IV, evidence of bioburden/infection, patient age, being nonambulatory, having renal transplant, paralysis, malnutrition, and/or patient hospitalization for any reason. CONCLUSIONS: Body and heel PrU Wound Healing Indices are comprehensive, user-friendly, and validated predictive models for likelihood of body and heel PrU healing. They can risk-stratify patients in clinical research trials, stratify patient data for quality reporting and benchmarking activities, and identify patients most likely to require advanced therapeutics to achieve healing. PMID- 26562205 TI - Strategic view of meaningful use plus final rule updates: part 3. PMID- 26562206 TI - Increase in incidence of congenital syphilis - United States, 2012-2014. AB - Congenital syphilis (CS) occurs when a mother infected with syphilis transmits the infection to her child during pregnancy. CS can cause severe illness, miscarriage, stillbirth, and early infant death. However, among pregnant women with syphilis who deliver after 20 weeks gestation, maternal treatment with penicillin is 98% effective at preventing CS (1). In the United States, the rate of CS decreased during 1991-2005 but increased slightly during 2005-2008 (2). To assess recent trends in CS, CDC analyzed national surveillance data reported during 2008-2014, calculated rates, and described selected characteristics of infants with CS and their mothers. The overall rate of reported CS decreased from 10.5 to 8.4 cases per 100,000 live births during 2008-2012, and then increased to 11.6 cases per 100,000 live births in 2014, the highest CS rate reported since 2001. From 2012 to 2014, reported cases and rates of CS increased across all regions of the United States. To reduce CS, the timely identification of and response to increases in syphilis among women of reproductive age and men who have sex with women are essential. All women should have access to quality prenatal care, including syphilis screening and adequate treatment, during pregnancy (3). PMID- 26562209 TI - Yield of Outpatient Sleep EEG for Epileptiform Alterations' Detection in Children. AB - PURPOSE: Ambulatory EEGs in children are frequently ordered as sleep studies. However, the yield according to different clinical situations has received little attention to date. The authors aimed to quantify the added value in terms of detection of epileptiform features of an EEG containing sleep, as compared with only wakefulness, according to the referral diagnoses. METHODS: The authors retrospectively selected consecutive outpatients' EEG recordings of patients between 6 months to 16 years old, performed between January 2014 and February 2015. The authors excluded those lacking at least 10 minutes of waking and/or at least 5 minutes of behavioral sleep. Interictal epileptiform activity (IEA) in wakefulness and sleep was compared among referral suspected diagnoses. Additional yield of sleep was considered if at least one of the following was observed: appearance of interictal epileptiform activity or increase by >50%; interictal epileptiform activity change in localization or morphology, seizure occurrence. RESULTS: A total of 425 recordings (mean age 6.9 +/- 4.7 years) were analyzed. Of them, 194 (45.6%) presented an additional yield during sleep, which was dependent on the occurrence of IEA during wakefulness: 77/251 (30.7%) in those without versus 117/174 (67.2%) in those with wakefulness IEA (P < 0.001, chi). The yield was markedly lower in studies performed for nonepileptic referral diagnoses (7% vs. 43% to 100%; P < 0.001, Fisher). CONCLUSIONS: When wakefulness EEG lacks epileptiform features, the yield of sleep EEG in our pediatric population appeared modest, especially in patients without a suspected epileptic syndrome. This information may be used to optimize the request of sleep EEG in children. PMID- 26562208 TI - Evaluation of Dry Sensors for Neonatal EEG Recordings. AB - PURPOSE: Neonatal seizures are a common neurologic diagnosis in neonatal intensive care units, occurring in approximately 14,000 newborns annually in the United States. Although the only reliable means of detecting and treating neonatal seizures is with an electroencephalography (EEG) recording, many neonates do not receive an EEG or experience delays in getting them. Barriers to obtaining neonatal EEGs include (1) lack of skilled EEG technologists to apply conventional wet electrodes to delicate neonatal skin, (2) poor signal quality because of improper skin preparation and artifact, and (3) extensive time needed to apply electrodes. Dry sensors have the potential to overcome these obstacles but have not previously been evaluated on neonates. METHODS: Sequential and simultaneous recordings with wet and dry sensors were performed for 1 hour on 27 neonates from 35 to 42.5 weeks postmenstrual age. Recordings were analyzed for correlation and amplitude and were reviewed by neurophysiologists. Performance of dry sensors on simulated vernix was examined. RESULTS: Analysis of dry and wet signals showed good time-domain correlation (reaching >0.8), given the nonsuperimposed sensor positions and similar power spectral density curves. Neurophysiologist reviews showed no statistically significant difference between dry and wet data on most clinically relevant EEG background and seizure patterns. There was no skin injury after 1 hour of dry sensor recordings. In contrast to wet electrodes, impedance and electrical artifact of dry sensors were largely unaffected by simulated vernix. CONCLUSIONS: Dry sensors evaluated in this study have the potential to provide high-quality, timely EEG recordings on neonates with less risk of skin injury. PMID- 26562211 TI - Low Drag Porous Ship with Superhydrophobic and Superoleophilic Surface for Oil Spills Cleanup. AB - To efficiently remove and recycle oil spills, we construct aligned ZnO nanorod arrays on the surface of the porous stainless steel wire mesh to fabricate a porous unmanned ship (PUS) with properties of superhydrophobicity, superoleophilicity, and low drag by imitating the structure of nonwetting leg of water strider. The superhydrophobicity of the PUS is stable, which can support 16.5 cm water column with pore size of 100 MUm. Water droplet can rebound without adhesion. In the process of oil/water separation, when the PUS contacts with oil, the oil is quickly pulled toward and penetrates into the PUS automatically. The superhydrophobicity and low water adhesion force of the PUS surface endow the PUS with high oil recovery capacity (above 94%) and drag-reducing property (31% at flowing velocity of 0.38m/s). In addition, the PUS has good corrosion resistance and reusability. We further investigate the wetting behavior of water and oil, oil recovery capacity, drag-reducing property, and corrosion resistance of the PUS after oil absorbed. The PUS surface changes significantly from superhydrophobic to hydrophobic after absorbing oil. However, the oil absorbed PUS possesses better drag-reducing property and corrosion resistance due to the changes of the motion state of the water droplets. PMID- 26562212 TI - Electrochemical Synthesis and Magnetic Properties of [Cu9W6]: The Ultimate Member of the Quindecanuclear Octacyanometallate-Based Transition-Metal Cluster? AB - [Cu9W6], synthesized by the electrochemical method, may be the ultimate member of the quindecanuclear octacyanometallate-based transition-metal cluster. Its single crystal structure and magnetic properties were characterized. PMID- 26562213 TI - Controllable Nonspecific Protein Adsorption by Charged Hyperbranched Polyglycerol Thin Films. AB - Antifouling thin films derived from charged hyperbranched polyglycerol (hbPG) layers were fabricated and evaluated. The anionic hbPG (a-hbPG) monolayers and cationic hbPG/anionic hbPG (c/a-hbPG) bilayers were adsorbed on the underlying self-assembled monolayers (SAMs) of cysteamine and 3-mercaptopropionic acid (3 MPA) by electrostatic interaction, respectively, and their procession was monitored by surface plasmon resonance spectroscopy (SPR). The adsorption of bovine serum albumin (BSA) and fibrinogen on the premade a-hbPG and c/a-hbPG thin films was measured and the capability of these thin films to resist nonspecific protein adsorption was evaluated by SPR as well. It is observed that the c/a-hbPG bilayer films possessed good antifouling properties. With c/a-hbPG bilayers consisting of higher molecular weight a-hbPG, the adsorption of BSA and fibrinogen were as low as 0.015 ng/mm(-2) and 0.0076 ng/mm(-2), respectively, comparable to the traditionally ultralow antifouling surfaces (<0.05 ng/mm(-2) of nonspecific protein adsorption). This work proved that the charged hbPG thin films can strongly reduce the nonspecific protein adsorption and have the promise for the antifouling coatings with improved performance. PMID- 26562214 TI - High-Efficiency Polymer LEDs with Fast Response Times Fabricated via Selection of Electron-Injecting Conjugated Polyelectrolyte Backbone Structure. AB - Imidazolium ionic side-group-containing fluorene-based conjugated polyelectrolytes (CPEs) with different pi-conjugated structures, poly[(9,9-bis(8' (3"-methyl-1"-imidazolium)octyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] dibromide (F8im-Br) and poly[(9,9-bis(8'-(3"-methyl-1"-imidazolium)octyl)-2,7 fluorene)-alt-(benzo(2,1,3)thiadiazol-4,8-diyl) dibromide (F8imBT-Br), are synthesized and utilized as an electron injection layer (EIL) in green-emitting F8BT polymer light-emitting diodes (PLEDs). Both CPE EIL devices significantly outperform Ca cathode devices; 17.9 cd A(-1) (at 3.8 V) and 16.6 lm W(-1) (at 3.0 V) for F8imBT-Br devices, 11.1 cd A(-1) (at 4.2 V) and 9.1 lm W(-1) (at 3.4 V) for F8im-Br devices, and 7.2 cd A(-1) (at 3.6 V) and 7.0 lm W(-1) (at 3.0 V) for Ca devices. Importantly, unlike the F8im-Br EIL devices, F8imBT-Br PLEDs exhibit much faster electroluminescence turn-on times (<10 MUs) despite both EILs possessing the same tethered imidazolium and mobile bromide ions. The F8imBT-Br devices represent, to the best of our knowledge, the highest efficiency in thin (70 nm) single-layer F8BT PLEDs in conventional device architecture with the fastest EL response time using CPE EIL with mobile ions. Our results clearly indicate the importance of an additional factor of EIL materials, specifically the conjugated backbone structure, to determine the device efficiency and response times. PMID- 26562215 TI - Dearomative Indole Cycloaddition Reactions of Aza-Oxyallyl Cationic Intermediates: Modular Access to Pyrroloindolines. AB - A regioselective dearomative aza-(3 + 2) cycloaddition reaction of substituted indoles with alpha-halohydroxamates has been developed. This transformation provides rapid access to highly functionalized pyrroloindolines that are represented in large number of bioactive compounds. The natural product, physostigmine, has been concisely synthesized utilizing this method. PMID- 26562216 TI - Synthesis of Functionalized Chromeno[2,3-b]pyrrol-4(1H)-ones by Silver-Catalyzed Cascade Reactions of Chromones/Thiochromones and Isocyanoacetates. AB - A novel and convenient approach to the synthesis of chromeno[2,3-b]pyrrol-4(1H) ones has been developed. Furthermore, the method involves a facile silver catalyzed cascade cyclization reaction including an intramolecular C-O bond formation. The silver salt acts as a key promoter. PMID- 26562217 TI - Development of Alkyne-Containing Pyrazolopyrimidines To Overcome Drug Resistance of Bcr-Abl Kinase. AB - Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-Abl(T315I) by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only Abl(T315I) in vitro but also Bcr-Abl(T315I) in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML. PMID- 26562219 TI - Neurotrophin-dependent plasticity of neurotransmitter segregation in the rat superior cervical ganglion in vivo. AB - Neurons are able to segregate transmitters to different axon endings. Segregation is a plastic neuronal feature; it can be modulated by synaptic environment. We have demonstrated that neurotrophin and other cellular factors regulate segregation in sympathetic neurons in culture. Herein we tested the hypothesis that sympathetic neurons in vivo are also capable to exhibit neurotrophin dependent plasticity of segregation. To explore the effect of neurotrophin on segregation, we reduced ganglionic NGF content by the transection of postganglionic nerves (axotomy) of the superior cervical ganglia. By immunohistochemistry, Western blot, and PCR analyses, we explored the effect of axotomy on the NGF and BDNF content of ganglionic neurons, and on the segregation extent of vesicular acetylcholine transporter (VAChT) and methionine enkephalin (mENK) in pre-ganglionic varicosities. We analyzed NGF-dependence of the changes found by applying exogenous NGF. Axotomy reduced ganglionic NGF and BDNF content, increased NGF transcripts, and increased VAChT-mENK segregation. Axotomy also increased the number of VAChT immunopositive varicosities, and caused the appearance of a population of VAChT-, mENK- or SV2-containing varicosities lacking Synaptophysin (Syn). Administration of NGF prevented changes in NGF content, kept NGF transcripts increased, and counteracted changes in segregation and in the number of cholinergic varicosities. The exogenous NGF did not preclude change in BDNF content or in the occurrence of the VAChT- or mENK-containing varicosities lacking Syn. Data demonstrate that segregation of transmitters in vivo is plastic and it is modulated by environmental signals like NGF. We propose a possible functional correlate of segregation plasticity in the sympathetic ganglia. (c) 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 832-846, 2016. PMID- 26562218 TI - Optical probes based on G protein-coupled receptors - added work or added value? AB - In 2003, the first report was published that presented proof of principle for a novel class of FRET biosensors for use in living cells. This novel sensor class was built on the base of GPCRs, which represent an integral transmembrane receptor family passing the membrane seven times and are thus also called the 7TM receptor family. As an estimated number of 30% of all marketed drugs exert their effects by modulating GPCR function, these initial reports promised the gain of novel insights into receptor function. Such FRET sensors have slowly, but progressively, made their way into the standard toolbox for GPCR research as several groups are now reporting on the generation and use of these sensors. By now, FRET sensors have been reported for 18 different GPCRs, and more are expected to be added. These particular receptor sensors have been used to investigate receptor dynamics in living cells to evaluate ligand binding and ligand efficacy in real time, to study voltage and mechanosensitivity of GPCRs or to study the influence of receptor polymorphisms on receptor function in real time. In this review we will describe the different design principles of these GPCR-based sensors and will summarize their current biological applications in living cells. PMID- 26562220 TI - Nerve ultrasound in electrophysiologically verified tarsal tunnel syndrome. AB - INTRODUCTION: Tarsal tunnel syndrome (TTS) arises from tibial nerve damage under the flexor retinaculum of the fibro-osseus tunnel at the medial malleolus. It is notoriously difficult to diagnose, as many other foot pathologies result in a similar clinical picture. We examined the additional value of nerve ultrasound in patients with tarsal tunnel syndrome confirmed by nerve conduction. METHODS: We performed a retrospective analysis of nerve ultrasound changes in electrophysiologically confirmed TTS spanning our records from 2007 to 2015. RESULTS: Nine feet with TTS were identified, all of which showed abnormal nerve ultrasound findings, which in 6 feet, led to identification of the underlying cause. CONCLUSIONS: This study shows that nerve ultrasound is abnormal in all cases of electrophysiologically verified TTS. The pattern of nerve abnormality is varied. This, and the fact that in the majority of patients causation was identified, suggests nerve ultrasound should form part of standard work-up for TTS. Muscle Nerve 53: 906-912, 2016. PMID- 26562221 TI - RAD sequencing reveals within-generation polygenic selection in response to anthropogenic organic and metal contamination in North Atlantic Eels. AB - Measuring the effects of selection on the genome imposed by human-altered environment is currently a major goal in ecological genomics. Given the polygenic basis of most phenotypic traits, quantitative genetic theory predicts that selection is expected to cause subtle allelic changes among covarying loci rather than pronounced changes at few loci of large effects. The goal of this study was to test for the occurrence of polygenic selection in both North Atlantic eels (European Eel, Anguilla anguilla and American Eel, A. rostrata), using a method that searches for covariation among loci that would discriminate eels from 'control' vs. 'polluted' environments and be associated with specific contaminants acting as putative selective agents. RAD-seq libraries resulted in 23 659 and 14 755 filtered loci for the European and American Eels, respectively. A total of 142 and 141 covarying markers discriminating European and American Eels from 'control' vs. 'polluted' sampling localities were obtained using the Random Forest algorithm. Distance-based redundancy analyses (db-RDAs) were used to assess the relationships between these covarying markers and concentration of 34 contaminants measured for each individual eel. PCB153, 4'4'DDE and selenium were associated with covarying markers for both species, thus pointing to these contaminants as major selective agents in contaminated sites. Gene enrichment analyses suggested that sterol regulation plays an important role in the differential survival of eels in 'polluted' environment. This study illustrates the power of combining methods for detecting signals of polygenic selection and for associating variation of markers with putative selective agents in studies aiming at documenting the dynamics of selection at the genomic level and particularly so in human-altered environments. PMID- 26562222 TI - Landfill leachate as a mirror of today's disposable society: Pharmaceuticals and other contaminants of emerging concern in final leachate from landfills in the conterminous United States. AB - Final leachates (leachate after storage or treatment processes) from 22 landfills in 12 states were analyzed for 190 pharmaceuticals and other contaminants of emerging concern (CECs), which were detected in every sample, with the number of CECs ranging from 1 to 58 (median = 22). In total, 101 different CECs were detected in leachate samples, including 43 prescription pharmaceuticals, 22 industrial chemicals, 15 household chemicals, 12 nonprescription pharmaceuticals, 5 steroid hormones, and 4 animal/plant sterols. The most frequently detected CECs were lidocaine (91%, local anesthetic), cotinine (86%, nicotine degradate), carisoprodol (82%, muscle relaxant), bisphenol A (77%, component of plastics and thermal paper), carbamazepine (77%, anticonvulsant), and N,N-diethyltoluamide (68%, insect repellent). Concentrations of CECs spanned 7 orders of magnitude, ranging from 2.0 ng/L (estrone) to 17,200,000 ng/L (bisphenol A). Concentrations of household and industrial chemicals were the greatest (~1000-1,000,000 ng/L), followed by plant/animal sterols (~1000-100,000 ng/L), nonprescription pharmaceuticals (~100-10,000 ng/L), prescription pharmaceuticals (~10-10,000 ng/L), and steroid hormones (~10-100 ng/L). The CEC concentrations in leachate from active landfills were significantly greater than those in leachate from closed, unlined landfills (p = 0.05). The CEC concentrations were significantly greater (p < 0.01) in untreated leachate compared with treated leachate. The CEC concentrations were significantly greater in leachate disposed to wastewater treatment plants from modern lined landfills than in leachate released to groundwater from closed, unlined landfills (p = 0.04). The CEC concentrations were significantly greater (p = 0.06) in the fresh leachate (leachate before storage or treatment) reported in a previous study compared with the final leachate sampled for the present study. PMID- 26562223 TI - Molecular Multipole Potential Energy Functions for Water. AB - Water is the most common liquid on this planet, with many unique properties that make it essential for life as we know it. These properties must arise from features in the charge distribution of a water molecule, so it is essential to capture these features in potential energy functions for water to reproduce its liquid state properties in computer simulations. Recently, models that utilize a multipole expansion located on a single site in the water molecule, or "molecular multipole models", have been shown to rival and even surpass site models with up to five sites in reproducing both the electrostatic potential around a molecule and a variety of liquid state properties in simulations. However, despite decades of work using multipoles, confusion still remains about how to truncate the multipole expansions efficiently and accurately. This is particularly important when using molecular multipole expansions to describe water molecules in the liquid state, where the short-range interactions must be accurate, because the higher order multipoles of a water molecule are large. Here, truncation schemes designed for a recent efficient algorithm for multipoles in molecular dynamics simulations are assessed for how well they reproduce results for a simple three site model of water when the multipole moments and Lennard-Jones parameters of that model are used. In addition, the multipole analysis indicates that site models that do not account for out-of-plane electron density overestimate the stability of a non-hydrogen-bonded conformation, leading to serious consequences for the simulated liquid. PMID- 26562224 TI - Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor. AB - DNA-encoded small-molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technology has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small molecule ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technology to membrane-associated targets and demonstrate the feasibility of selecting DNA tagged, small-molecule ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell. PMID- 26562226 TI - Response to Cederbaum. PMID- 26562225 TI - Computational evaluation of exome sequence data using human and model organism phenotypes improves diagnostic efficiency. AB - PURPOSE: Medical diagnosis and molecular or biochemical confirmation typically rely on the knowledge of the clinician. Although this is very difficult in extremely rare diseases, we hypothesized that the recording of patient phenotypes in Human Phenotype Ontology (HPO) terms and computationally ranking putative disease-associated sequence variants improves diagnosis, particularly for patients with atypical clinical profiles. METHODS: Using simulated exomes and the National Institutes of Health Undiagnosed Diseases Program (UDP) patient cohort and associated exome sequence, we tested our hypothesis using Exomiser. Exomiser ranks candidate variants based on patient phenotype similarity to (i) known disease-gene phenotypes, (ii) model organism phenotypes of candidate orthologs, and (iii) phenotypes of protein-protein association neighbors. RESULTS: Benchmarking showed Exomiser ranked the causal variant as the top hit in 97% of known disease-gene associations and ranked the correct seeded variant in up to 87% when detectable disease-gene associations were unavailable. Using UDP data, Exomiser ranked the causative variant(s) within the top 10 variants for 11 previously diagnosed variants and achieved a diagnosis for 4 of 23 cases undiagnosed by clinical evaluation. CONCLUSION: Structured phenotyping of patients and computational analysis are effective adjuncts for diagnosing patients with genetic disorders.Genet Med 18 6, 608-617. PMID- 26562228 TI - Predicting prosthetic prescription after major lower-limb amputation. AB - We describe prosthetic limb prescription in the first year following lower-limb amputation and examine the relationship between amputation level, geographic region, and prosthetic prescription. We analyzed 2005 to 2010 Department of Veterans Affairs (VA) Inpatient and Medical Encounters SAS data sets, Vital Status death data, and National Prosthetic Patient Database data for 9,994 Veterans who underwent lower-limb amputation at a VA hospital. Descriptive statistics and bivariates were examined. Cox proportional hazard models identified factors associated with prosthetic prescription. Analyses showed that amputation level was associated with prosthetic prescription. The hazard ratios (HRs) were 1.41 for ankle amputation and 0.46 for transfemoral amputation compared with transtibial amputation. HRs for geographic region were Northeast = 1.49, Upper Midwest = 1.26, and West = 1.39 compared with the South (p < 0.001). African American race, longer length of hospital stay, older age, congestive heart failure, paralysis, other neurological disease, renal failure, and admission from a nursing facility were negatively associated with prosthetic prescription. Being married was positively associated. After adjusting for patient characteristics, people with ankle amputation were most likely to be prescribed a prosthesis and people with transfemoral amputation were least likely. Geographic variation in prosthetic prescription exists in the VA and further research is needed to explain why. PMID- 26562227 TI - Improving hearing loss gene testing: a systematic review of gene evidence toward more efficient next-generation sequencing-based diagnostic testing and interpretation. AB - PURPOSE: With next generation sequencing technology improvement and cost reductions, it has become technically feasible to sequence a large number of genes in one diagnostic test. This is especially relevant for diseases with large genetic and/or phenotypic heterogeneity, such as hearing loss. However, variant interpretation remains the major bottleneck. This is further exacerbated by the lack in the clinical genetics community of consensus criteria for defining the evidence necessary to include genes on targeted disease panels or in genomic reports, and the consequent risk of reporting variants in genes with no relevance to disease. METHODS: We describe a systematic evidence-based approach for assessing gene-disease associations and for curating relevant genes for different disease aspects, including mode of inheritance, phenotypic severity, and mutation spectrum. RESULTS: By applying this approach to clinically available hearing loss gene panels with a total of 163 genes, we show that a significant number (45%) of genes lack sufficient evidence of association with disease and thus are expected to increase uncertainty and patient anxiety, in addition to intensifying the interpretation burden. Information about all curated genes is summarized. Our retrospective analysis of 539 hearing loss cases tested by our previous OtoGenomeV2 panel demonstrates the impact of including genes with weak disease association in laboratory wet-bench and interpretation processes. CONCLUSION: Our study is, to our knowledge, the first to highlight the urgent need for defining the clinical validity of gene-disease relationships for more efficient and accurate clinical testing and reporting.Genet Med 18 6, 545-553. PMID- 26562229 TI - CT of Gastric Emergencies. AB - Abdominal pain, nausea, and vomiting are common presenting symptoms among adult patients seeking care in the emergency department, and, with the increased use of computed tomography (CT) to image patients with these complaints, radiologists will more frequently encounter a variety of emergent gastric pathologic conditions on CT studies. Familiarity with the CT appearance of emergent gastric conditions is important, as the clinical presentation is often nonspecific and the radiologist may be the first to recognize gastric disease as the cause of a patient's symptoms. Although endoscopy and barium fluoroscopy remain important tools for evaluating patients with suspected gastric disease in the outpatient setting, compared with CT these modalities enable less comprehensive evaluation of patients with nonspecific complaints and are less readily available in the acute setting. Endoscopy is also more invasive than CT and has greater potential risks. Although the mucosal detail of CT is relatively poor compared with barium fluoroscopy or endoscopy, CT can be used with the appropriate imaging protocols to identify inflammatory conditions of the stomach ranging from gastritis to peptic ulcer disease. In addition, CT can readily demonstrate the various complications of gastric disease, including perforation, obstruction, and hemorrhage, which may direct further clinical, endoscopic, or surgical management. We will review the normal anatomy of the stomach and discuss emergent gastric disease with a focus on the usual clinical presentation, typical imaging appearance, and differentiating features, as well as potential imaging pitfalls. PMID- 26562230 TI - CT Evaluation of Acute Enteritis and Colitis: Is It Infectious, Inflammatory, or Ischemic?: Resident and Fellow Education Feature. PMID- 26562231 TI - Extratesticular Fibrous Pseudotumor. PMID- 26562232 TI - A Primer on the Physical Principles of Tissue Harmonic Imaging. AB - Tissue harmonic imaging (THI) is a routinely used component of diagnostic ultrasonography (US). In this method, higher-frequency harmonic waves produced by nonlinear fundamental US wave propagation are used to generate images that contain fewer artifacts than those seen on conventional fundamental wave US tissue imaging. Harmonic frequencies are integer multiples of the fundamental frequency. The majority of current clinical US systems use second harmonic echoes for THI image formation. Image processing techniques (ie, bandwidth receive filtering, pulse inversion, side-by-side phase cancellation, and pulse-coded harmonics) are used to eliminate the fundamental frequency echoes, and the remaining harmonic frequency data are used to generate the diagnostic image. Advantages of THI include improved signal-to-noise ratio and reduced artifacts produced by side lobes, grating lobes, and reverberation. THI has been accepted in US practice, and variations of the technology are available on most US systems typically used for diagnostic imaging in radiologic practice. Differential THI is a further improvement that combines the advantages of THI, including superior tissue definition and reduced speckle artifact, with the greater penetration of lower frequency US, which permits high-quality harmonic imaging at greater depth than could previously be performed with conventional THI. PMID- 26562234 TI - Three-dimensional Physical Modeling: Applications and Experience at Mayo Clinic. AB - Radiologists will be at the center of the rapid technologic expansion of three dimensional (3D) printing of medical models, as accurate models depend on well planned, high-quality imaging studies. This article outlines the available technology and the processes necessary to create 3D models from the radiologist's perspective. We review the published medical literature regarding the use of 3D models in various surgical practices and share our experience in creating a hospital-based three-dimensional printing laboratory to aid in the planning of complex surgeries. PMID- 26562235 TI - High-Resolution US of Rheumatologic Diseases. AB - For the past 15 years, high-resolution ultrasonography (US) is being routinely and increasingly used for initial evaluation and treatment follow-up of rheumatologic diseases. This imaging technique is performed by using high frequency linear transducers and has proved to be a powerful diagnostic tool in evaluation of articular erosions, simple and complex joint and bursal effusions, tendon sheath effusions, and synovitis, with results comparable to those of magnetic resonance imaging, excluding detection of bone marrow edema. Crystal deposition diseases including gouty arthropathy and calcium pyrophosphate deposition disease (CPPD) have characteristic appearances at US, enabling differentiation between these two diseases and from inflammatory arthropathies. Enthesopathy, which frequently accompanies psoriatic and reactive arthritis, also has a characteristic appearance at high-resolution US, distinguishing these two entities from other inflammatory and metabolic arthropathies. The presence of Doppler signal in examined joints, bursae, and tendon sheaths indicates active synovitis. Microbubble echo contrast agents augment detection of tissue vascularity and may act in the future as a drug delivery vehicle. Frequently, joint, tendon sheath, and bursal fluid aspirations and therapeutic injections are performed under US guidance. The authors describe the high-resolution US technique including gray-scale, color or power Doppler, and contrast agent enhanced US that is used in evaluation of rheumatologic diseases of the wrist and hand and the ankle and foot in their routine clinical practice. This article demonstrates imaging findings of normal joints, rheumatoid arthritis, gouty arthritis, CPPD, psoriatic and reactive arthritis, and osteoarthritis. PMID- 26562236 TI - Fibrous Dysplasia of the Rib: AIRP Best Cases in Radiologic-Pathologic Correlation. PMID- 26562233 TI - Medical 3D Printing for the Radiologist. AB - While use of advanced visualization in radiology is instrumental in diagnosis and communication with referring clinicians, there is an unmet need to render Digital Imaging and Communications in Medicine (DICOM) images as three-dimensional (3D) printed models capable of providing both tactile feedback and tangible depth information about anatomic and pathologic states. Three-dimensional printed models, already entrenched in the nonmedical sciences, are rapidly being embraced in medicine as well as in the lay community. Incorporating 3D printing from images generated and interpreted by radiologists presents particular challenges, including training, materials and equipment, and guidelines. The overall costs of a 3D printing laboratory must be balanced by the clinical benefits. It is expected that the number of 3D-printed models generated from DICOM images for planning interventions and fabricating implants will grow exponentially. Radiologists should at a minimum be familiar with 3D printing as it relates to their field, including types of 3D printing technologies and materials used to create 3D-printed anatomic models, published applications of models to date, and clinical benefits in radiology. Online supplemental material is available for this article. PMID- 26562238 TI - Optimizing Digital Mammographic Image Quality for Full-Field Digital Detectors: Artifacts Encountered during the QC Process. AB - Early detection of breast cancer through routine mammographic screening has been shown to reduce mortality from breast cancer by up to 30% in multiple studies. However, this reduction of mortality is possible only with careful attention to image quality by the medical physicist, radiologic technologist, and interpreting radiologist. The accepted quality control (QC) processes for analog mammography are well established. However, now that use of digital units is widespread in both the United States and internationally, information regarding the necessary steps and the inherent challenges that might be encountered at each step needs to be elucidated. In this review, the essential steps of the QC process for digital mammography are reviewed, with special attention to the possible problems that can occur during the QC process, many of which can lead to image artifacts. For each of the daily, weekly, monthly, and semiannual QC tests, we review the steps and expected performance and provide examples of some of the common artifacts that may be encountered. Understanding the components of the QC process and recognizing problems that may result in a suboptimal image is critical to ensure optimal image quality in an effort to maximize early detection of breast cancer. PMID- 26562237 TI - Radiology of Cleft Lip and Palate: Imaging for the Prenatal Period and throughout Life. AB - Recent advances in prenatal imaging have made possible the in utero diagnosis of cleft lip and palate and associated deformities. Postnatal diagnosis of cleft lip is made clinically, but imaging still plays a role in detection of associated abnormalities, surgical treatment planning, and screening for or surveillance of secondary deformities. This article describes the clinical entities of cleft lip with or without cleft palate (CLP) and isolated cleft palate and documents their prenatal and postnatal appearances at radiography, ultrasonography (US), magnetic resonance (MR) imaging, and computed tomography (CT). Imaging protocols and findings for prenatal screening, detection of associated anomalies, and evaluation of secondary deformities throughout life are described and illustrated. CLP and isolated cleft palate are distinct entities with shared radiologic appearances. Prenatal US and MR imaging can depict clefting of the lip or palate and associated anomalies. While two- and three-dimensional US often can depict cleft lip, visualization of cleft palate is more difficult, and repeat US or fetal MR imaging should be performed if cleft palate is suspected. Postnatal imaging can assist in identifying associated abnormalities and dentofacial deformities. Dentofacial sequelae of cleft lip and palate include missing and supernumerary teeth, oronasal fistulas, velopharyngeal insufficiency, hearing loss, maxillary growth restriction, and airway abnormalities. Secondary deformities can often be found incidentally at imaging performed for other purposes, but detection is necessary because they may have considerable implications for the patient. PMID- 26562240 TI - Imaging of Ancient Egyptian Animal Mummies. AB - Human mummies have long been studied by using imaging as a primary investigative method. Mummified animal remains from ancient Egypt are less well researched, yet much can be learned about species diversity and the methods of preservation. Noninvasive imaging methods enable mummy bundles to remain intact, with no detrimental physical effects, thus ensuring protection of a valuable archaeological resource. This article is based on the research experience gathered during 13 years (2000-2012) with 152 animal mummies held in the collections of 17 museums in the United Kingdom. Conventional radiography, computed radiography, digital radiography, and computed tomography (CT) available in the clinical setting were used to assess the value of each imaging modality in the study of animal mummies and related material. Radiography proved to be an excellent research method that provided initial insight into the contents of the mummy bundle, and CT contributed additional useful detail in some cases. Paleoradiologic analyses enabled information on mummy bundle contents to be proved, including the nature of the skeletal remains and the methods of mummification. An optimum method involving radiography and CT is described. PMID- 26562241 TI - Imaging of Atlanto-Occipital and Atlantoaxial Traumatic Injuries: What the Radiologist Needs to Know. AB - Approximately one-third of all cervical spine injuries involve the craniocervical junction (CCJ). Composed of the occiput and the first two cervical vertebrae, this important anatomic landmark, in conjunction with an intricate ligamentous complex, is essential to maintaining the stability of the cervical spine. The atlantoaxial joint is the most mobile portion of the spine, predominantly relying on the ligamentous framework for stability at that level. As acute onsite management of trauma patients continues to improve, CCJ injuries, which often lead to death onsite where the injury occurred, are increasingly being encountered in the emergency department. Understanding the anatomy of the CCJ is crucial in properly evaluating the cervical spine, allowing the radiologist to assess its stability in the trauma setting. The imaging findings of important CCJ injuries, such as atlanto-occipital dissociation, occipital condyle fractures, atlas fractures with transverse ligament rupture, atlantoaxial distraction, and traumatic rotatory subluxation, are important to recognize in the acute setting, often dictating patient management. Thin-section multidetector computed tomography with sagittal and coronal reformats is the study of choice in evaluating the extent of injury, allowing the radiologist to thoroughly evaluate the stability of the cervical spine. Furthermore, magnetic resonance (MR) imaging is increasingly being used to evaluate the spinal soft tissues and ligaments, and to identify associated spinal cord injury, if present. MR imaging is also indicated in patients whose neurologic status cannot be evaluated within 48 hours of injury. . PMID- 26562239 TI - Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy. AB - Although rectal and anal cancers are anatomically close, they are distinct entities with different histologic features, risk factors, staging systems, and treatment pathways. Imaging is at the core of initial clinical staging of these cancers and most commonly includes magnetic resonance imaging for local-regional staging and computed tomography for evaluation of metastatic disease. The details of the primary tumor and involvement of regional lymph nodes are crucial in determining if and how radiation therapy should be used in treatment of these cancers. Unfortunately, available imaging modalities have been shown to have imperfect accuracy for identification of nodal metastases and imaging features other than size. Staging of nonmetastatic rectal cancers is dependent on the depth of invasion (T stage) and the number of involved regional lymph nodes (N stage). Staging of nonmetastatic anal cancers is determined according to the size of the primary mass and the combination of regional nodal sites involved; the number of positive nodes at each site is not a consideration for staging. Patients with T3 rectal tumors and/or involvement of perirectal, mesenteric, and internal iliac lymph nodes receive radiation therapy. Almost all anal cancers warrant use of radiation therapy, but the extent and dose of the radiation fields is altered on the basis of both the size of the primary lesion and the presence and extent of nodal involvement. The radiologist must recognize and report these critical anatomic and staging distinctions, which affect use of radiation therapy in patients with anal and rectal cancers. PMID- 26562242 TI - Normal and Abnormal US Findings in Early First-Trimester Pregnancy: Review of the Society of Radiologists in Ultrasound 2012 Consensus Panel Recommendations. AB - Since being introduced more than 30 years ago, endovaginal ultrasonography (US) and quantitative testing of serum levels of the beta subunit of human chorionic gonadotropin have become the standard means of establishing the presence of normal intrauterine pregnancy (IUP), failed IUP, and ectopic pregnancy. Appropriate use of these powerful tools requires clear, standardized interpretations based on conservative criteria to protect both the pregnancy and the mother. Since diagnoses are assigned earlier and available medical treatments for ectopic pregnancy and failed IUP are expanding, emphasis must carefully shift toward watchful waiting when the mother is clinically stable and a definitive location for the pregnancy cannot be established with US. To this end and to prevent inadvertent harm to early normal pregnancies, the Society of Radiologists in Ultrasound convened a consensus panel of radiologists, obstetricians, and emergency medicine physicians in 2012 with the goal of reviewing current literature and clinical practices and formulating modern criteria and terminology for the various first-trimester outcomes. PMID- 26562243 TI - Additional Radiologic Clue to Diagnosing Hepatic Lymphoma. PMID- 26562244 TI - Uber and Us: Radiology and On Demand Platforms, with Commentary from Dr Heilman: Practice Corner. PMID- 26562245 TI - Congratulations to the 2015 RSNA Outstanding Educator: Kay H. Vydareny, MD. PMID- 26562247 TI - Mycophenolate Mofetil Therapy in Refractory Inflammatory Eye Disease. AB - PURPOSE: To study the efficacy and incidence of treatment-related side effects of mycophenolate mofetil (MMF) therapy in patients with noninfectious inflammatory eye diseases. METHODS: Retrospective cohort study of 27 Chilean patients treated for noninfectious inflammatory eye diseases using MMF therapy over a 10-year period. Main outcome measures were: ability to control ocular inflammation and to taper prednisone to <=10 mg daily (treatment success); incidence of treatment related side effects. RESULTS: The proportion of patients with sustained control of inflammation was 81.48% at 6 months. Additionally 55.56% and 22.22% of patients succeeded in tapering their prednisone to 5-10 mg/day and <5 mg/day, at 6 months. Two patients developed a neoplasia during MMF therapy; however, this cohort is too small to interpret the significance of this relation to MMF treatment. CONCLUSIONS: MMF seems to be an effective corticosteroid-sparing agent with an acceptable safety profile. PMID- 26562249 TI - Perception and the Social Psychology of 'The Dress'. PMID- 26562248 TI - Combined Ang-2 and VEGF serum levels: holding hands as a new integral biomarker in non-small-cell lung cancers. AB - AIM: Evaluate if serum levels of VEGF and Ang-2 are correlated in non-small-cell lung cancers (NSCLCs) and its implications in the diagnostic and prognostic of the disease. PATIENTS & METHODS: Unselected cohort of 145 NSCLC patients and 30 control individuals. The serum levels of Ang-2 and VEGF of each patient were measured by ELISA prior to treatment. RESULTS & CONCLUSIONS: Serum levels of Ang 2 and VEGF are correlated (p < 0.0001). High serum levels of Ang-2 and VEGF isolated and both combined (high(Ang-2/VEGF)) correlate with likelihood of presenting NSCLC (p = 0.016; p = 0.003; p < 0.0001, respectively). Serum levels of Ang-2 and high(Ang-2/VEGF) but not VEGF alone are independent prognostic factors (p = 0.001; p = 0.619; p = 0.005). High(Ang-2/VEGF) serum levels could be exploited as a new valuable integral biomarker in NSCLC. PMID- 26562250 TI - Spatiotemporal Relationships among Audiovisual Stimuli Modulate Auditory Facilitation of Visual Target Discrimination. AB - Sensory information is multimodal; through audiovisual interaction, task irrelevant auditory stimuli tend to speed response times and increase visual perception accuracy. However, mechanisms underlying these performance enhancements have remained unclear. We hypothesize that task-irrelevant auditory stimuli might provide reliable temporal and spatial cues for visual target discrimination and behavioral response enhancement. Using signal detection theory, the present study investigated the effects of spatiotemporal relationships on auditory facilitation of visual target discrimination. Three experiments were conducted where an auditory stimulus maintained reliable temporal and/or spatial relationships with visual target stimuli. Results showed that perception sensitivity (d') to visual target stimuli was enhanced only when a task-irrelevant auditory stimulus maintained reliable spatiotemporal relationships with a visual target stimulus. When only reliable spatial or temporal information was contained, perception sensitivity was not enhanced. These results suggest that reliable spatiotemporal relationships between visual and auditory signals are required for audiovisual integration during a visual discrimination task, most likely due to a spread of attention. These results also indicate that auditory facilitation of visual target discrimination follows from late-stage cognitive processes rather than early stage sensory processes. PMID- 26562251 TI - The Achromatic Object-Colour Manifold is Three-Dimensional. AB - When in shadow, the achromatic object colours appear different from when they are in light. This immediate observation was quantitatively confirmed by Logvinenko and Maloney (2006, Perception & Psychophysics, 68, 76-83) who, using multidimensional scaling (MDS), showed the two-dimensionality of achromatic object colours. As their experiments included only cast shadows, a question arises: is this also the case for attached shadows? Recently, Madigan and Brainard (2014) argued in favour of the negative answer. However, they also failed to confirm the two-dimensionality for cast shadows. To resolve this issue, an experiment was conducted in which observers rated the dissimilarity between achromatic Munsell chips presented in light and in shadows of both types. Specifically, the chips were presented in four conditions: in front in light; at slant in light; in front in shadow; and at slant in shadow. MDS analysis of the obtained dissimilarities confirmed the two-dimensionality of achromatic colours for both types of shadow. Furthermore, the dimension induced by the cast shadow (shadowedness) was found to be different from that induced by the attached shadow (shading). In the three-dimensional MDS output configuration these were represented by clearly different dimensions. This quantitatively supports a fact, well-known to artists, that attached and cast shadows are experienced as different phenomenological entities. It is argued that a shading gradient is perceptually experienced as shape (ie spatial relief). PMID- 26562252 TI - The Processing Speed of Scene Categorization at Multiple Levels of Description: The Superordinate Advantage Revisited. AB - Recent studies have sought to determine which levels of categories are processed first in visual scene categorization and have shown that the natural and man-made superordinate-level categories are understood faster than are basic-level categories. The current study examined the robustness of the superordinate-level advantage in a visual scene categorization task. A go/no-go categorization task was evaluated with response time distribution analysis using an ex-Gaussian template. A visual scene was categorized as either superordinate or basic level, and two basic-level categories forming a superordinate category were judged as either similar or dissimilar to each other. First, outdoor/ indoor groups and natural/man-made were used as superordinate categories to investigate whether the advantage could be generalized beyond the natural/man-made boundary. Second, a set of images forming a superordinate category was manipulated. We predicted that decreasing image set similarity within the superordinate-level category would work against the speed advantage. We found that basic-level categorization was faster than outdoor/indoor categorization when the outdoor category comprised dissimilar basic-level categories. Our results indicate that the superordinate level advantage in visual scene categorization is labile across different categories and category structures. PMID- 26562253 TI - Signal Detection Measures Cannot Distinguish Perceptual Biases from Response Biases. AB - A common conceptualization of signal detection theory (SDT) holds that if the effect of an experimental manipulation is truly perceptual, then it will necessarily be reflected in a change in d' rather than a change in the measure of response bias. Thus, if an experimental manipulation affects the measure of bias, but not d', then it is safe to conclude that the manipulation in question did not affect perception but instead affected the placement of the internal decision criterion. However, the opposite may be true: an effect on perception may affect measured bias while having no effect on d'. To illustrate this point, we expound how signal detection measures are calculated and show how all biases-including perceptual biases-can exert their effects on the criterion measure rather than on d'. While d' can provide evidence for a perceptual effect, an effect solely on the criterion measure can also arise from a perceptual effect. We further support this conclusion using simulations to demonstrate that the Muller-Lyer illusion, which is a classic visual illusion that creates a powerful perceptual effect on the apparent length of a line, influences the criterion measure without influencing d'. For discrimination experiments, SDT is effective at discriminating between sensitivity and bias but cannot by itself determine the underlying source of the bias, be it perceptual or response based. PMID- 26562254 TI - Orientation and Spatial Frequency Selectivity following Adaptation: A Reaction Time Study. AB - The aim of the study was to determine orientation and spatial frequency sensitivity using reaction times (RTs) in an adaptation paradigm. Simple RTs were measured to the onset of a Gabor patch (SD = 1.2 deg, spatial frequency = 4 cycles deg(-1)). Observers adapted for 10 s to a 4 cycles deg(-1) grating presented at a series of orientations (0, 2, 5, 10, 22.5, 45, 90 degrees ) or spatial frequencies (+/-0.5, 1, and 2 octaves). The contrast of the test grating was 4x each participant's unadapted threshold. The effect of adaptation was evaluated by transforming RTs to effective contrast reduction using RT-based contrast response functions. RTs increased by between ~ 100 ms to 150 ms when the test and adapting gratings were of the same orientation or spatial frequency. The effect became less pronounced as the difference in orientation or spatial frequency increased. The average bandwidths for orientation and spatial frequency were 17.4 degrees and 1.24 octaves, respectively. The method has some advantages over traditional approaches. It reveals a rapid time course of adaptation recovery with a half-life of about 13 s to 23 s. RTs form a rapid and easily implemented technique for assessing the underlying physiological mechanisms that control adaptation at suprathreshold levels of contrast. PMID- 26562255 TI - Flicker-Defined Forms in the Ternus Display. AB - Odic and Pratt (2008, Perception, 37, 1790-1804) proposed that the type of movement seen in the bistable Ternus display depends on the elements' temporal summation of contrast relative to the background. To test this theory, participants viewed a flicker-defined Ternus display where the elements had no temporal summation of contrast. Participants also viewed a luminance-defined control condition. Five interstimulus intervals (ISIs) (0, 20, 40, 60, and 80 ms) and two stimulus durations (SDs) (200 and 400 ms) were used in each condition. If temporal summation of contrast does not influence perceived group and end-to-end movement in flicker-defined forms, it was expected that the frequency of their reports would be equal to those in the luminance- defined control condition at the same ISIs and SDs. As predicted, the main effect of condition was not significant and participants reported both percepts at expected rates in both conditions, contrary to the predictions of Odic and Pratt (2008). PMID- 26562256 TI - The Headscarf Effect Revisited: Further Evidence for a Culture-Based Internal Face Processing Advantage. AB - Encoding the internal features of unfamiliar faces poses a perceptual challenge that occasionally results in face recognition errors. Extensive experience with faces framed by a headscarf may, however, enhance perceivers' ability to process internal facial information. To examine this claim empirically, participants in the United Arab Emirates and the United States of America completed a standard part-whole face recognition task. Accuracy on the task was examined using a 2 (perceiver culture: Emirati vs American) x 2 (face race: Arab vs white) x 2 (probe type: part vs whole) x 3 (probe feature: eyes vs nose vs mouth) mixed measures analysis of variance. As predicted, Emiratis outperformed Americans on the administered task. Although their recognition advantage occurred regardless of probe type, it was most pronounced for Arab faces and for trials that captured the processing of nose or mouth information. The findings demonstrate that culture-based experiences hone perceivers' face processing skills. PMID- 26562257 TI - Review: Human Factors in Lighting. PMID- 26562258 TI - Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity. AB - We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects. PMID- 26562259 TI - GnRH Episodic Secretion Is Altered by Pharmacological Blockade of Gap Junctions: Possible Involvement of Glial Cells. AB - Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 MUM 18-alpha-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-alpha-glycyrrhetinic acid washout. PMID- 26562260 TI - Conditional Deletion of Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Reveals Its Essential Role in Chondrocyte Function and Endochondral Bone Formation. AB - The hypoxic growth plate cartilage requires hypoxia-inducible factor (HIF) mediated pathways to maintain chondrocyte survival and differentiation. HIF proteins are tightly regulated by prolyl hydroxylase domain-containing protein 2 (Phd2)-mediated proteosomal degradation. We conditionally disrupted the Phd2 gene in chondrocytes by crossing Phd2 floxed mice with type 2 collagen-alpha1-Cre transgenic mice and found massive increases (>50%) in the trabecular bone mass of long bones and lumbar vertebra of the Phd2 conditional knockout (cKO) mice caused by significant increases in trabecular number and thickness and reductions in trabecular separation. Cortical thickness and tissue mineral density at the femoral middiaphysis of the cKO mice were also significantly increased. Dynamic histomorphometric analyses revealed increased longitudinal length and osteoid surface per bone surface in the primary spongiosa of the cKO mice, suggesting elevated conversion rate from hypertrophic chondrocytes to mineralized bone matrix as well as increased bone formation in the primary spongiosa. In the secondary spongiosa, bone formation measured by mineralizing surface per bone surface and mineral apposition rate were not changed, but resorption was slightly reduced. Increases in the mRNA levels of SRY (sex determining region Y)-box 9, osterix (Osx), type 2 collagen, aggrecan, alkaline phosphatase, bone sialoprotein, vascular endothelial growth factor, erythropoietin, and glycolytic enzymes in the growth plate of cKO mice were detected by quantitative RT-PCR. Immunohistochemistry revealed an increased HIF-1alpha protein level in the hypertrophic chondrocytes of cKO mice. Infection of chondrocytes isolated from Phd2 floxed mice with adenoviral Cre resulted in similar gene expression patterns as observed in the cKO growth plate chondrocytes. Our findings indicate that Phd2 suppresses endochondral bone formation, in part, via HIF-dependent mechanisms in mice. PMID- 26562261 TI - Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle. AB - Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5'adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)-Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3 (LC3), Sequestosome 1 (p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5'adenosine monophosphate-activated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation. PMID- 26562262 TI - XBP1 Regulates the Biosynthetic Capacity of the Mammary Gland During Lactation by Controlling Epithelial Expansion and Endoplasmic Reticulum Formation. AB - Cells composing the mammary secretory compartment have evolved a high capacity to secrete not only proteins but also triglycerides and carbohydrates. This feature is illustrated by the mouse, which can secrete nearly twice its own weight in milk proteins, triglycerides and lactose over a short 20-day lactation. The coordination of synthesis and export of products in other secretory cells is orchestrated in part by the transcription factor X-box binding protein 1 (XBP1). To assess the role of XBP1 in mammary epithelial cells (MEC), we studied floxed XBP1 female mice lacking (wild type; WT) or expressing the Cre recombinase under the control of the ovine beta-lactoglobulin promoter (DeltaXBP1(MEC)). Pregnant DeltaXBP1(MEC) females had morphologically normal mammary development and gave birth to the same number of pups as WT mice. Their litters, however, suffered a weight gain deficit by lactation day 3 (L3)3 that grew to 80% by L14. DeltaXBP1(MEC) dams had only modest changes in milk composition (-21% protein, +24% triglyceride) and in the expression of associated genes in isolated MEC. By L5, WT glands were fully occupied by dilated alveoli, whereas DeltaXBP1(MEC) glands contained fewer, mostly unfilled alveoli and retained a prominent adipocyte population. The smaller epithelial compartment in DeltaXBP1(MEC) glands was explained by lower MEC proliferation and increased apoptosis. Finally, endoplasmic reticulum ribbons were less abundant in DeltaXBP1(MEC) at pregnancy day 18 and failed to increase in abundance by L5. Collectively, these results show that XBP1 is required for MEC population expansion during lactation and its ability to develop an elaborate endoplasmic reticulum compartment. PMID- 26562266 TI - Electronic brachytherapy: overused and overpriced? PMID- 26562264 TI - Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice. AB - Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1beta levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and beta-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men. PMID- 26562265 TI - Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. AB - The PTH receptor type 1 (PTHR1) mediates the actions of two endogenous polypeptide ligands, PTH and PTHrP, and thereby plays key roles in bone biology. Based on its capacity to stimulate bone formation, the peptide fragment PTH (1 34) is currently in use as therapy for osteoporosis. Abaloparatide (ABL) is a novel synthetic analog of human PTHrP (1-34) that holds promise as a new osteoporosis therapy, as studies in animals suggest that it can stimulate bone formation with less of the accompanying bone resorption and hypercalcemic effects that can occur with PTH (1-34). Recent studies in vitro suggest that certain PTH or PTHrP ligand analogs can distinguish between two high-affinity PTHR1 conformations, R(0) and RG, and that efficient binding to R(0) results in prolonged signaling responses in cells and prolonged calcemic responses in animals, whereas selective binding to RG results in more transient responses. As intermittent PTH ligand action is known to favor the bone-formation response, whereas continuous ligand action favors the net bone-resorption/calcemic response, we hypothesized that ABL binds more selectively to the RG vs the R(0) PTHR1 conformation than does PTH (1-34), and thus induces more transient signaling responses in cells. We show that ABL indeed binds with greater selectivity to the RG conformation than does PTH (1-34), and as a result of this RG bias, ABL mediates more transient cAMP responses in PTHR1-expressing cells. The findings provide a plausible mechanism (ie, transient signaling via RG selective binding) that can help account for the favorable anabolic effects that ABL has on bone. PMID- 26562267 TI - Medically unlikely edits. PMID- 26562263 TI - Both Estrogen and Androgen Modify the Response to Activation of Neurokinin-3 and kappa-Opioid Receptors in Arcuate Kisspeptin Neurons From Male Mice. AB - Gonadal steroids regulate the pattern of GnRH secretion. Arcuate kisspeptin (kisspeptin, neurokinin B, and dynorphin [KNDy]) neurons may convey steroid feedback to GnRH neurons. KNDy neurons increase action potential firing upon the activation of neurokinin B receptors (neurokinin-3 receptor [NK3R]) and decrease firing upon the activation of dynorphin receptors (kappa-opioid receptor [KOR]). In KNDy neurons from intact vs castrated male mice, NK3R-mediated stimulation is attenuated and KOR-mediated inhibition enhanced, suggesting gonadal secretions are involved. Estradiol suppresses spontaneous GnRH neuron firing in male mice, but the mediators of the effects on firing in KNDy neurons are unknown. We hypothesized the same gonadal steroids affecting GnRH firing pattern would regulate KNDy neuron response to NK3R and KOR agonists. To test this possibility, extracellular recordings were made from KNDy neurons in brain slices from intact, untreated castrated or castrated adult male mice treated in vivo with steroid receptor agonists. As observed previously, the stimulation of KNDy neurons by the NK3R agonist senktide was attenuated in intact vs castrated mice and suppression by dynorphin was enhanced. In contrast to observations of steroid effects on the GnRH neuron firing pattern, both estradiol and DHT suppressed senktide-induced KNDy neuron firing and enhanced the inhibition caused by dynorphin. An estrogen receptor-alpha agonist but not an estrogen receptor-beta agonist mimicked the effects of estradiol on NK3R activation. These observations suggest the steroid modulation of responses to activation of NK3R and KOR as mechanisms for negative feedback in KNDy neurons and support the contribution of these neurons to steroid sensitive elements of a GnRH pulse generator. PMID- 26562268 TI - Physician skin examinations for melanoma screening. AB - A variety of estimates of the value and impact of physician skin examinations (PSEs) in screening for melanoma have been published. Although current melanoma screening guidelines vary, new evidence supports improved melanoma outcomes associated with PSEs. In this systematic review, we evaluated 5 observational studies of the impact of PSEs on melanoma thickness at diagnosis and melanoma mortality rates. Although definitive evidence from randomized controlled trials supporting improved health outcomes associated with PSEs is lacking, these well designed observational studies have found PSEs to be correlated with thinner melanomas at diagnosis and reduced melanoma mortality rates. PMID- 26562269 TI - An analysis of the clinical trial landscape for cutaneous melanoma. AB - Recognizing current trends and obstacles in melanoma clinical trial development is critical to future progress in this field. This article examines the melanoma research enterprise to identify changing trends and potential barriers to success. All trials registered at ClinicalTrials.gov after September 2005 were evaluated for possible inclusion. A total of 777 interventional trials designed specifically for cutaneous melanoma patients were included. Geographic trial distribution as well as disease state and type of intervention were analyzed and compared among each group. ClinicalTrials.gov is an invaluable tool to study the research enterprise. Further studies are needed on prevention and early detection of melanoma in the curative setting, a critical role for dermatologists. PMID- 26562270 TI - Evaluation of gender as a clinically relevant outcome variable in the treatment of onychomycosis with efinaconazole topical solution 10. AB - Although there are limited data available on gender as an outcome variable in the treatment of onychomycosis, differences in disease prevalence and impact in males versus females have been observed. This article provides a gender subgroup analysis based on results from recent studies evaluating the efficacy, safety, and tolerability of efinaconazole topical solution 10% in the treatment of onychomycosis. Data were collected from two 52-week, prospective, multicenter, randomized, double-blind studies of patients ?(age range, 18-70 years) randomized to receive either efinaconazole topical solution 10% or vehicle for treatment of onychomycosis. Results from this analysis indicated that once-daily application of efinaconazole topical solution 10% may provide a useful topical option for treatment of mild to moderate toenail onychomycosis, especially in female patients. PMID- 26562271 TI - What is your diagnosis? Idiopathic guttate hypomelanosis. PMID- 26562272 TI - Syringoid eccrine carcinoma. PMID- 26562273 TI - Therapies for actinic keratosis with a focus on cosmetic outcomes. AB - Actinic keratosis (AK) is a commonly encountered premalignant epidermal lesion that has a predilection to manifest on highly visible areas such as the face, head, and hands. Lesions may be cosmetically unappealing and have been reported to reduce patients' quality of life (QOL), but appropriate treatment can resolve these issues. In this article, we review the efficacy of the most commonly utilized treatments for AKs including topical medications, procedural modalities, and light-based therapies, and we discuss the relevant cosmetic considerations and outcomes. PMID- 26562274 TI - Erythema induratum of Bazin presenting as peripheral neuropathy. AB - Erythema induratum of Bazin (EIB) is a rare tuberculid that typically affects middle-aged women. We report a unique case of EIB in a 57-year-old Hispanic woman who presented with recurrent painful plaques and nodules on the lower extremities, specifically on the pretibial area of the legs and dorsal aspect of the feet, with a severe burning sensation on the feet that resolved after antituberculosis therapy. We review the characteristics of EIB and examine how the unique presentation of peripheral neuropathy may relate to the pathophysiology of this disease. PMID- 26562275 TI - Characterization of knuckle (Garrod) pads using optical coherence tomography in vivo. PMID- 26562276 TI - Oral lichen planus with malignant transformation to invasive squamous cell carcinoma. PMID- 26562277 TI - Extensive skin necrosis from suspected levamisole-contaminated cocaine. PMID- 26562278 TI - Granulomatous cheilitis: a stiff upper lip. PMID- 26562279 TI - Enhancing dermatology education: resident presentation opportunities. AB - Dermatology residency is a time to maximize educational experiences, which include opportunities to attend academic meetings and present research and clinical cases. In this article, resident presentation opportunities at major academic dermatology meetings are reviewed. PMID- 26562280 TI - Type 1 neurofibromatosis (von Recklinghausen disease). AB - Type 1 neurofibromatosis (NF1), or von ?Recklinghausen disease, is a genetic disorder that is well known for its clinical features. ?Effective treatment modalities for NF1 have not yet been established. The advent of new treatment options for NF1 such as topical vitamin D3 analogues, lovastatin, rapamycin (or sirolimus), and imatinib mesylate has added new dimensions that require further investigation to provide the greatest benefit to patients. PMID- 26562281 TI - Painful skin lesions on the hands following black henna application. PMID- 26562282 TI - Vegetative sacral plaque in a patient with human immunodeficiency virus. PMID- 26562283 TI - A New Role Discovered for a Well-Known Clock Protein. AB - A new study adds further complexity to the mammalian circadian clock by revealing that the CRY protein has an additional unsuspected feedback role in facilitating a crucial regulatory phosphorylation event. Read the Research Article. PMID- 26562284 TI - Common-mask guided image reconstruction (c-MGIR) for enhanced 4D cone-beam computed tomography. AB - Compared to 3D cone beam computed tomography (3D CBCT), the image quality of commercially available four-dimensional (4D) CBCT is severely impaired due to the insufficient amount of projection data available for each phase. Since the traditional Feldkamp-Davis-Kress (FDK)-based algorithm is infeasible for reconstructing high quality 4D CBCT images with limited projections, investigators had developed several compress-sensing (CS) based algorithms to improve image quality. The aim of this study is to develop a novel algorithm which can provide better image quality than the FDK and other CS based algorithms with limited projections. We named this algorithm 'the common mask guided image reconstruction' (c-MGIR).In c-MGIR, the unknown CBCT volume is mathematically modeled as a combination of phase-specific motion vectors and phase-independent static vectors. The common-mask matrix, which is the key concept behind the c MGIR algorithm, separates the common static part across all phase images from the possible moving part in each phase image. The moving part and the static part of the volumes were then alternatively updated by solving two sub-minimization problems iteratively. As the novel mathematical transformation allows the static volume and moving volumes to be updated (during each iteration) with global projections and 'well' solved static volume respectively, the algorithm was able to reduce the noise and under-sampling artifact (an issue faced by other algorithms) to the maximum extent. To evaluate the performance of our proposed c MGIR, we utilized imaging data from both numerical phantoms and a lung cancer patient. The qualities of the images reconstructed with c-MGIR were compared with (1) standard FDK algorithm, (2) conventional total variation (CTV) based algorithm, (3) prior image constrained compressed sensing (PICCS) algorithm, and (4) motion-map constrained image reconstruction (MCIR) algorithm, respectively. To improve the efficiency of the algorithm, the code was implemented with a graphic processing unit for parallel processing purposes.Root mean square error (RMSE) between the ground truth and reconstructed volumes of the numerical phantom were in the descending order of FDK, CTV, PICCS, MCIR, and c-MGIR for all phases. Specifically, the means and the standard deviations of the RMSE of FDK, CTV, PICCS, MCIR and c-MGIR for all phases were 42.64 +/- 6.5%, 3.63 +/- 0.83%, 1.31% +/- 0.09%, 0.86% +/- 0.11% and 0.52 % +/- 0.02%, respectively. The image quality of the patient case also indicated the superiority of c-MGIR compared to other algorithms.The results indicated that clinically viable 4D CBCT images can be reconstructed while requiring no more projection data than a typical clinical 3D CBCT scan. This makes c-MGIR a potential online reconstruction algorithm for 4D CBCT, which can provide much better image quality than other available algorithms, while requiring less dose and potentially less scanning time. PMID- 26562285 TI - Comment on "Scaling properties of information-theoretic quantities in density functional reactivity theory" by C. Rong, T. Lu, P. W. Ayers, P. K. Chattaraj and S. Liu, Phys. Chem. Chem. Phys., 2015, 17, 4977-4988. AB - The scaling properties of density functionals are key for fundamentally understanding density functional theory. Accordingly, the dependence of density functionals on the number of particles is of paramount relevance. The numerical exploration by Rong et al. addressed N-scaling for a set of quantum information quantities; they found linear relationships between each one of them and the electronic population for atoms, molecules, and atoms in molecules. The main motivation for their computational work was that the theoretical scaling of these quantities is unknown; however, these scaling properties can be analytically determined. Here I reveal the derivation of the N-scaling rules for the quantities studied by Rong et al. by following the procedure introduced in Comput. Theor. Chem., 2015, 1053, 38. In addition, a new atomic scaling rule explains the linear relationship between atomic populations and atomic values of the same quantum information quantities. PMID- 26562286 TI - Strategies for Controlled Ovarian Stimulation in the Setting of Ovarian Aging. AB - In the context of assisted reproduction, the term ovarian aging is often used to refer to declining potential of ovaries to produce oocytes in adequate number or quality in response to controlled ovarian stimulation (COS). Different aspects of COS have been modified with the intention to increase the number and quality of oocytes obtained for in vitro fertilization. In the setting of ovarian aging, suppression of the luteinizing hormone (LH) surge with gonadotropin-releasing hormone (GnRH) antagonist or short GnRH agonist protocol and stimulation with a daily gonadotropin dosage of <= 300 IU/day seem to be appropriate first choices, and there is a strong need for well-designed randomized controlled trials investigating effects of addition of LH activity, estradiol priming, transdermal testosterone administration, and growth hormone supplementation. Given the lack of high-quality evidence showing effectiveness of one approach over another, other factors such as duration of stimulation, total gonadotropin consumption and cost of medication, patient friendliness, and possible side effect profiles must be considered in tailoring the COS protocol according to each individual's needs and desires. PMID- 26562287 TI - Oocyte Cryopreservation as a Preventive Measure for Age-Related Fertility Loss. AB - The increased desire to achieve higher educational, career, or financial goals and not having met a suitable partner are the main reasons why women are postponing parenthood to later stages in life. Not being aware of the age-related decline in fertility and the presence of novel and effective fertility preservation strategies are contributing factors to the increased incidence of childlessness at later stages of life. Oocyte cryopreservation has recently been introduced as a means of increasing the probability of motherhood at advanced ages, should attempts at natural conception fail. It is likely to be the most effective when performed in patients younger than 35 years with a good ovarian reserve. Preconceptional counseling of women by medical professionals, education of young adolescents at schools, organization of public health campaigns, and presentation of fertility health information through the media are strategies suggested to increase public awareness on the age-related decline in fertility and avoid its possible consequences. PMID- 26562288 TI - Metabolic Determinants of Mitochondrial Function in Oocytes. AB - Mitochondrial production of cellular energy is essential to oocyte function, zygote development and successful continuation of pregnancy. This review focuses on several key functions of healthy oocyte mitochondria and the effect of pathologic states such as aging, oxidative stress and apoptosis on these functions. The effect of these abnormal conditions is presented in terms of clinical presentations, specifically maternal obesity, diminished ovarian reserve and assisted reproductive technologies. PMID- 26562289 TI - Impaired DNA Repair as a Mechanism for Oocyte Aging: Is It Epigenetically Determined? AB - DNA damage is one of the most common insults that challenge all cells, and more so in resting cell-like oocytes. Increased DNA damage in aged oocyte has been shown to negatively impact the reproductive outcomes. The underlying molecular mechanism is still not completely comprehended, but based on the literature, this decline in the aging oocyte is attributed to impaired DNA repair and epigenetic modifications of these genes with increasing age. In this review, we discuss these molecular alterations and the epigenetic modifications in the DNA double strand break repair gene expressions as a mechanism of oocyte aging. PMID- 26562290 TI - An Analysis of Lateral Crural Repositioning and Its Effect on Alar Rim Position. AB - IMPORTANCE: Cephalically malpositioned lateral crura are a frequent cause of alar rim retraction during both primary and revision rhinoplasty. OBJECTIVE: To demonstrate the efficacy of lateral crural repositioning as an isolated maneuver as and combined with adjunctive grafts for lowering the alar rim. DESIGN, SETTING, AND PARTICIPANTS: From August through December 2014, we retrospectively reviewed the cases of 54 patients (102 hemi-noses) who had lateral crural repositioning performed by the same surgeon between 2007 and 2013. Only patients with standardized photographs taken preoperatively and at least 6 months postoperatively were included in the study. INTERVENTIONS: All primary and revision cases were completed via an open rhinoplasty approach and had lateral crural repositioning performed. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative photographs were compared using Adobe Photoshop CS via a modified Gunter technique to measure the degree of alar rim retraction on lateral views. The change in angle was then calculated, and statistical analysis conducted using a paired t test. RESULTS: A total of 54 patients (102 hemi-noses) met inclusion criteria; 42 (79%) were women, and the average patient age was 41.3 years. Forty five (83%) of the cases were revision rhinoplasties, and the average time to obtaining postoperative photographs was 11.3 months. The mean (SD) anterior nostril apex angles preoperatively (31.3 degrees [8.9 degrees ]) and postoperatively (24.5 degrees [6.8 degrees ]) indicated a net decrease of 6.8 degrees (P < .001). Excluding patients who had other rim-lowering grafts (alar rim and/or composite grafts), we saw a similar result comparing preoperative (31.1 degrees [8.2 degrees ]) and postoperative (24.5 degrees [6.7 degrees ]) angles, with a net decrease of 6.6 degrees degrees (P < .001). When examining patients who underwent lateral crural repositioning alone compared with those who also had lateral crural strut grafts, we saw a decrease of 6.9 degrees (P < .001) and 6.7 degrees degrees (P < .001), respectively. CONCLUSIONS AND RELEVANCE: Repositioning of the lower lateral cartilages results in a statistically significant lowering of the alar rim. Our data suggest that when combined with lateral crural repositioning, the addition of adjunctive grafts does not add significantly to the rim-lowering effect. LEVEL OF EVIDENCE: 3. PMID- 26562291 TI - Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins. AB - Non-structural protein 1 (NS1) is one of the most enigmatic proteins of the Dengue virus (DENV), playing distinct functions in immune evasion, pathogenesis and viral replication. The recently reported crystal structure of DENV NS1 revealed its peculiar three-dimensional fold; however, detailed information on NS1 function at different steps of the viral replication cycle is still missing. By using the recently reported crystal structure, as well as amino acid sequence conservation, as a guide for a comprehensive site-directed mutagenesis study, we discovered that in addition to being essential for RNA replication, DENV NS1 is also critically required for the production of infectious virus particles. Taking advantage of a trans-complementation approach based on fully functional epitope tagged NS1 variants, we identified previously unreported interactions between NS1 and the structural proteins Envelope (E) and precursor Membrane (prM). Interestingly, coimmunoprecipitation revealed an additional association with capsid, arguing that NS1 interacts via the structural glycoproteins with DENV particles. Results obtained with mutations residing either in the NS1 Wing domain or in the beta-ladder domain suggest that NS1 might have two distinct functions in the assembly of DENV particles. By using a trans-complementation approach with a C-terminally KDEL-tagged ER-resident NS1, we demonstrate that the secretion of NS1 is dispensable for both RNA replication and infectious particle production. In conclusion, our results provide an extensive genetic map of NS1 determinants essential for viral RNA replication and identify a novel role of NS1 in virion production that is mediated via interaction with the structural proteins. These studies extend the list of NS1 functions and argue for a central role in coordinating replication and assembly/release of infectious DENV particles. PMID- 26562292 TI - Risk Model-Guided Antiemetic Prophylaxis vs Physician's Choice in Patients Receiving Chemotherapy for Early-Stage Breast Cancer: A Randomized Clinical Trial. AB - IMPORTANCE: Despite multiple patient-centered factors being associated with the risk of chemotherapy-induced nausea and vomiting (CINV), these factors are rarely considered when making antiemetic recommendations. OBJECTIVE: To compare risk model-guided (RMG) antiemetic prophylaxis with physician's choice (PC) in patients receiving chemotherapy for early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of 324 patients with early-stage breast cancer undergoing chemotherapy (cyclophosphamide and an anthracycline) for the first time at 2 specialty cancer care centers in Ottawa from April 10, 2012, to September 2, 2014. Patients were randomized to either the RMG arm (n = 154) or the PC control arm (n = 170). Prior to each cycle of chemotherapy patients in the RMG group were categorized as low or high risk for CINV, and their antiemetic treatments were adjusted accordingly. INTERVENTIONS: Patients considered to be at low risk received standard dexamethasone and a 5-HT3 antagonist, while those at high risk also received aprepitant with or without olanzapine, based on their risk level. The PC control group received antiemetic agents according to the treating physician's discretion. MAIN OUTCOMES AND MEASURES: The primary end points were control of both nausea and vomiting in the acute posttreatment period (first 24 hours after therapy) and in the delayed posttreatment period (days 2-5 after therapy). RESULTS: The total numbers of chemotherapy cycles delivered in the RMG and PC control groups were 497 and 551 respectively. In the acute period, significantly more patients in the RMG group reported no nausea (53.7% [95% CI, 49.2%-58.1%] vs 41.6% [95% CI, 37.4%-45.3%]; P < .001) and no vomiting (91.8% [95% CI, 89.0%-94.0%] vs 82.2% [95% CI, 78.8%-85.3%]; P < .001) compared with the PC control group. Similarly, significantly more patients in the RMG group reported no nausea (39.6% [95% CI, 35.3%-44.1%] vs 30.7% [95% CI, 26.8%-34.7%]; P = .01) and no vomiting (87.1% [95% CI, 83.8%-90.0%) vs 78.0% [95% CI, 74.3% 81.4%]; P < .001) in the delayed period respectively. CONCLUSIONS AND RELEVANCE: In this trial, the RMG antiemetic prophylaxis led to improved control of acute and delayed CINV compared with physician's choice of therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01913990. PMID- 26562293 TI - The Cotton WRKY Gene GhWRKY41 Positively Regulates Salt and Drought Stress Tolerance in Transgenic Nicotiana benthamiana. AB - WRKY transcription factors constitute a very large family of proteins in plants and participate in modulating plant biological processes, such as growth, development and stress responses. However, the exact roles of WRKY proteins are unclear, particularly in non-model plants. In this study, Gossypium hirsutum WRKY41 (GhWRKY41) was isolated and transformed into Nicotiana benthamiana. Our results showed that overexpression of GhWRKY41 enhanced the drought and salt stress tolerance of transgenic Nicotiana benthamiana. The transgenic plants exhibited lower malondialdehyde content and higher antioxidant enzyme activity, and the expression of antioxidant genes was upregulated in transgenic plants exposed to osmotic stress. A beta-glucuronidase (GUS) staining assay showed that GhWRKY41 was highly expressed in the stomata when plants were exposed to osmotic stress, and plants overexpressing GhWRKY41 exhibited enhanced stomatal closure when they were exposed to osmotic stress. Taken together, our findings demonstrate that GhWRKY41 may enhance plant tolerance to stress by functioning as a positive regulator of stoma closure and by regulating reactive oxygen species (ROS) scavenging and the expression of antioxidant genes. PMID- 26562294 TI - The Type of Breast Reconstruction May Not Influence Patient Satisfaction in the Chinese Population: A Single Institutional Experience. AB - BACKGROUND: The goal of this study was to evaluate patient satisfaction with four common types of breast reconstruction performed at our institution: latissimus dorsi myocutaneous (LDM) flap reconstruction with or without implants, pedicled transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction, and free deep inferior epigastric perforator (DIEP) flap reconstruction. METHODS: A custom survey consisting of questions that assessed general and aesthetic satisfaction was sent to patients who had undergone breast reconstruction in the last 5 years. The clinical data and details of the surgery were also collected from the patients who returned the surveys. We compared satisfaction rates across the four breast reconstruction types and analyzed the effects of various factors on overall general and aesthetic satisfaction rates using a binary logistic regression model. RESULT: A total of 207 (72%) patients completed the questionnaires. Overall, significant differences in general and aesthetic satisfaction among the four procedures were not observed. A multivariate analysis revealed that the factor "complications" (p = 0.001) played a significant role in general satisfaction and that the factors "> 2 years since reconstruction" (p = 0.043) and "age > 35 years" (p = 0.05) played significant roles in overall aesthetic satisfaction. CONCLUSION: The present study demonstrated that the type of breast reconstruction might not influence satisfaction in Chinese patients. PMID- 26562296 TI - How Visuo-Spatial Mental Imagery Develops: Image Generation and Maintenance. AB - Two experiments examined the nature of visuo-spatial mental imagery generation and maintenance in 4-, 6-, 8-, 10-year old children and adults (N = 211). The key questions were how image generation and maintenance develop (Experiment 1) and how accurately children and adults coordinate mental and visually perceived images (Experiment 2). Experiment 1 indicated that basic image generation and maintenance abilities are present at 4 years of age but the precision with which images are generated and maintained improves particularly between 4 and 8 years. In addition to increased precision, Experiment 2 demonstrated that generated and maintained mental images become increasingly similar to visually perceived objects. Altogether, findings suggest that for simple tasks demanding image generation and maintenance, children attain adult-like precision younger than previously reported. This research also sheds new light on the ability to coordinate mental images with visual images in children and adults. PMID- 26562297 TI - How does the label "epileptic" influence attitudes toward epilepsy? AB - PURPOSE: The purpose of our research was to study the possible differences in attitudes toward epilepsy based on the label used: "person"/"child with epilepsy" vs. "epileptic"/"epileptic child". METHODS: Two randomly assigned groups of college-preparatory high school students were questioned using anonymous questionnaires about their demographics, knowledge on epilepsy and attitudes toward epilepsy. Attitudes were measured using three general attitude questions and a six item modified version of the Bogardus social distance scale. Two versions of the questionnaire were identical except for the term "person"/"child with epilepsy" in first group (group A) being replaced with the term "epileptic"/"epileptic child" in the second one (group B). Mann-Whitney test was used to compare attitude scores between groups. RESULTS: There were 425 subjects in total, 208 in group A and 217 in group B. The results on the Social distance scale indicated significantly more negative attitudes in group B (p=0.008). Subjects in group B also expressed more negative attitudes than those in group A when asked about sharing a room with a person with epilepsy (p=0.005) and marrying a person with epilepsy, either themselves (p=0.033) or when the person getting married is someone close to them (p=0.024). CONCLUSION: In conclusion, using term "epileptic" can evoke more negative attitudes toward a person with epilepsy and this seems to be especially true for more intimate life domains (cohabitation or marriage), while in more impersonal domains (such as communicating and working with a person with epilepsy), no significant influence of the label on attitudes was proven. PMID- 26562295 TI - Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System. AB - Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID- 26562299 TI - A Re-Examination of the History of Etiologic Confusion between Dengue and Chikungunya. AB - Contrary to the perception of many researchers that the recent invasion of chikungunya (CHIK) in the Western Hemisphere marked the first episode in history, a recent publication reminded them that CHIK had prevailed in the West Indies and southern regions of the United States from 1827-1828 under the guise of "dengue" (DEN), and that many old outbreaks of so-called "dengue" actually represented the CHIK cases erroneously identified as "dengue." In hindsight, this confusion was unavoidable, given that the syndromes of the two diseases-transmitted by the same mosquito vector in urban areas-are very similar, and that specific laboratory based diagnostic techniques for these diseases did not exist prior to 1940. While past reviewers reclassified problematic "dengue" outbreaks as CHIK, primarily based on manifestation of arthralgia as a marker of CHIK, they neither identified the root cause of the alleged misdiagnosis nor did they elaborate on the negative consequences derived from it. This article presents a reconstructed history of the genesis of the clinical definition of dengue by emphasizing problems with the definition, subsequent confusion with CHIK, and the ways in which physicians dealt with the variation in dengue-like ("dengue") syndromes. Then, the article identifies in those records several factors complicating reclassification, based on current practice and standards. These factors include terms used for characterizing joint problems, style of documenting outbreak data, frequency of manifestation of arthralgia, possible involvement of more than one agent, and occurrence of the principal vector. The analysis of those factors reveals that while some of the old "dengue" outbreaks, including the 1827-1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other "dengue" outbreaks to CHIK is difficult because of a combination of the absence of pathognomonic syndrome in these diseases and conflicting background information. PMID- 26562298 TI - Eye Movements Index Implicit Memory Expression in Fear Conditioning. AB - The role of contingency awareness in simple associative learning experiments with human participants is currently debated. Since prior work suggests that eye movements can index mnemonic processes that occur without awareness, we used eye tracking to better understand the role of awareness in learning aversive Pavlovian conditioning. A complex real-world scene containing four embedded household items was presented to participants while skin conductance, eye movements, and pupil size were recorded. One item embedded in the scene served as the conditional stimulus (CS). One exemplar of that item (e.g. a white pot) was paired with shock 100 percent of the time (CS+) while a second exemplar (e.g. a gray pot) was never paired with shock (CS-). The remaining items were paired with shock on half of the trials. Participants rated their expectation of receiving a shock during each trial, and these expectancy ratings were used to identify when (i.e. on what trial) each participant became aware of the programmed contingencies. Disproportionate viewing of the CS was found both before and after explicit contingency awareness, and patterns of viewing distinguished the CS+ from the CS-. These observations are consistent with "dual process" models of fear conditioning, as they indicate that learning can be expressed in patterns of viewing prior to explicit contingency awareness. PMID- 26562300 TI - Localization, expression and role of Orexin A and its receptor in testes of neonatal mice. AB - Orexin A (OXA), a hypothalamic neuropeptide, and its receptor (OX1R) are primarily expressed in lateral hypothalamus and are involved in the control of various biological functions. Expressions of OXA and OX1R have also been reported in peripheral organs like gastrointestinal and genital tracts. In the present study, expressions of OXA and OX1R have been observed in the testis of Parkes strain neonatal mice by semi-quantitative RT-PCR and western blot analyses. Immunohistochemical study also revealed their presence on spermatogonia, Sertoli cells and in the interstitium of the testis. In order to understand the role of OXA and OX1R in testicular development, an in vitro study was also performed. For this, binding of OXA to OX1R was blocked using OX1R specific antagonist, SB 334867. Eighteen mice were sacrificed and their testes were cultured in complete media containing vehicle and two doses (0.1 and 4.0MUg/ml media) of SB-334867 for 72h in CO2 incubator at 37 degrees C. At the end of culture period, testes were used for western blot and RT-PCR analyses to study the expression of various markers of gonadal development, such as steroidogenic factor 1 (SF-1), Wilms' tumor 1 (Wt1), Mullerian inhibiting substance (MIS) and stem cell factor (SCF). Further, expressions of OXA, OX1R and glucose transporter 3 (GLUT 3) were also studied. A marked increase in the expression of SF-1 and a decrease in the expression of Wt1 at both transcript and protein levels were noted, while there was a decrease in the expression of SCF and MIS at transcript level at both doses of the antagonist; this suggests that blockage of OXA binding to OX1R by SB 334867 affects testicular development. The decrease in expressions of OXA, OX1R and GLUT 3 in the test is in response to both doses of the antagonist points to their down-regulation causing inefficient uptake of glucose by the testicular cells, thereby affecting gonadal development. In conclusion, our results suggest that the binding of OXA to OX1R is important for the development of the testis. PMID- 26562301 TI - Frozen embryos? Torpor during pregnancy in the Tasmanian short-beaked echidna Tachyglossus aculeatus setosus. AB - We studied the interaction between torpor and reproduction in free-ranging female Tasmanian echidnas using a combination of techniques including urogenital smears, hormone analysis, ultrasonography, external temperature loggers and camera traps. Male echidnas initiated mating activity by locating hibernating females. All females that mated or were disturbed by males prior to July 27 re-entered hibernation, including many that were pregnant. Pregnant females only entered hibernation in early pregnancy when plasma progesterone concentrations were about twice basal and progesterone then remained constant during torpor. By re-entering hibernation pregnant females extended their gestation period and delayed egg laying. Progesterone peaked 4-6days before egg-laying, then dropped rapidly. PMID- 26562302 TI - Mutational Hotspot of TET2, IDH1, IDH2, SRSF2, SF3B1, KRAS, and NRAS from Human Systemic Mastocytosis Are Not Conserved in Canine Mast Cell Tumors. AB - INTRODUCTION: Both canine cutaneous mast cell tumor (MCT) and human systemic mastocytosis (SM) are characterized by abnormal proliferation and accumulation of mast cells in tissues and, frequently, by the presence of activating mutations in the receptor tyrosine kinase V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (c-KIT), albeit at different incidence (>80% in SM and 10-30% in MCT). In the last few years, it has been discovered that additional mutations in other genes belonging to the methylation system, the splicing machinery and cell signaling, contribute, with c-KIT, to SM pathogenesis and/or phenotype. In the present study, the mutational profile of the Tet methylcytosine dioxygenase 2 (TET2), the isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2), the serine/arginine-rich splicing factor 2 (SRSF2), the splicing factor 3b subunit 1 (SF3B1), the Kirsten rat sarcoma viral oncogene homolog (KRAS) and the neuroblastoma RAS viral oncogene homolog (NRAS), commonly mutated in human myeloid malignancies and mastocytosis, was investigated in canine MCTs. METHODS: Using the Sanger sequencing method, a cohort of 75 DNA samples extracted from MCT biopsies already investigated for c-KIT mutations were screened for the "human like" hot spot mutations of listed genes. RESULTS: No mutations were ever identified except for TET2 even if with low frequency (2.7%). In contrast to what is observed in human TET2 no frame-shift mutations were found in MCT samples. CONCLUSION: Results obtained in this preliminary study are suggestive of a substantial difference between human SM and canine MCT if we consider some target genes known to be involved in the pathogenesis of human SM. PMID- 26562303 TI - Decadal Trend in Agricultural Abandonment and Woodland Expansion in an Agro Pastoral Transition Band in Northern China. AB - Land use land cover (LULC) changes frequently in ecotones due to the large climate and soil gradients, and complex landscape composition and configuration. Accurate mapping of LULC changes in ecotones is of great importance for assessment of ecosystem functions/services and policy-decision support. Decadal or sub-decadal mapping of LULC provides scenarios for modeling biogeochemical processes and their feedbacks to climate, and evaluating effectiveness of land use policies, e.g. forest conversion. However, it remains a great challenge to produce reliable LULC maps in moderate resolution and to evaluate their uncertainties over large areas with complex landscapes. In this study we developed a robust LULC classification system using multiple classifiers based on MODIS (Moderate Resolution Imaging Spectroradiometer) data and posterior data fusion. Not only does the system create LULC maps with high statistical accuracy, but also it provides pixel-level uncertainties that are essential for subsequent analyses and applications. We applied the classification system to the Agro pasture transition band in northern China (APTBNC) to detect the decadal changes in LULC during 2003-2013 and evaluated the effectiveness of the implementation of major Key Forestry Programs (KFPs). In our study, the random forest (RF), support vector machine (SVM), and weighted k-nearest neighbors (WKNN) classifiers outperformed the artificial neural networks (ANN) and naive Bayes (NB) in terms of high classification accuracy and low sensitivity to training sample size. The Bayesian-average data fusion based on the results of RF, SVM, and WKNN achieved the 87.5% Kappa statistics, higher than any individual classifiers and the majority-vote integration. The pixel-level uncertainty map agreed with the traditional accuracy assessment. However, it conveys spatial variation of uncertainty. Specifically, it pinpoints the southwestern area of APTBNC has higher uncertainty than other part of the region, and the open shrubland is likely to be misclassified to the bare ground in some locations. Forests, closed shrublands, and grasslands in APTBNC expanded by 23%, 50%, and 9%, respectively, during 2003-2013. The expansion of these land cover types is compensated with the shrinkages in croplands (20%), bare ground (15%), and open shrublands (30%). The significant decline in agricultural lands is primarily attributed to the KFPs implemented in the end of last century and the nationwide urbanization in recent decade. The increased coverage of grass and woody plants would largely reduce soil erosion, improve mitigation of climate change, and enhance carbon sequestration in this region. PMID- 26562304 TI - VGF Peptide Profiles in Type 2 Diabetic Patients' Plasma and in Obese Mice. AB - To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74+/-10 vs. 167+/-28, and 92+/-10 vs. 191+/-19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3+/-0.2 vs. 4.6+/-0.3, 22+/-3.5 vs. 34+/-1.3, and 48+/-7 vs. 100+/-7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment. PMID- 26562305 TI - Parasite Glycobiology: A Bittersweet Symphony. PMID- 26562306 TI - E-mails in a Psychiatric Practice: Why Patients Send Them and How Psychiatrists Respond. AB - CONTEXT: Little is known about what prompts patients to use e-mail with their physicians and how physicians respond to these e-mails. OBJECTIVE: To identify the main reasons why patients e-mail and to learn how psychiatrists manage these e-mails as part of these patients' overall care. DESIGN: One hundred patient initiated e-mails to each of two psychiatrists in a group practice were studied retrospectively for primary reason for the e-mail and for psychiatrists' handling of each e-mail. Other data were collected to assess how representative the e mailing patients were of the psychiatrists' patient panels. RESULTS: Age, sex, and diagnoses of the e-mailers were similar to our overall panels. The most common reasons for e-mailing were refill requests (19.5%), questions about prescribed medication (16.5%), and worsening of symptoms (11.5%). The modal e mail was a patient with attention-deficit/hyperactivity disorder requesting a refill. The psychiatrists' most common responses were authorizing a refill (25%), reassurance (22%), and making or moving up a scheduled appointment (16%). For all patients who reported a worsening of symptoms, responses, communicated by e-mail or telephone, included a combination of an earlier appointment and/or change in medication or dose and/or referral for psychotherapy. Both psychiatrists found e mail to be an efficient enhancement of their practice, and it was inferred that this was also a satisfying mechanism for patients. CONCLUSION: Physician-patient communication via e-mail is timesaving for both, and the benefits to patient care should reassure physicians who are wary of using e-mail in their practice. Potential risks to patients without face-to-face or telephone contact appear to be minimal. PMID- 26562307 TI - Effect of Advancing Age and Multiple Chronic Conditions on Mortality in Patients with End-Stage Renal Disease after Implantable Cardioverter-Defibrillator Placement. AB - CONTEXT: There is insufficient information on the effect that advancing age and multiple chronic conditions (MCC) have on mortality after placement of an implantable cardioverter-defibrillator in patients with end-stage renal disease (ESRD) vs non-ESRD. OBJECTIVE: To assess whether a differential effect of age and MCC exists between ESRD and non-ESRD. DESIGN: Population-based, retrospective cohort study using data from the national Kaiser Permanente Cardiac Device Registry of patients who underwent placement of an implantable cardioverter defibrillator between January 1, 2007, and December 31, 2013. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: Of 7825 patients with implantable cardioverter-defibrillator placement, ESRD-affected patients constituted 4.0% of the cohort (n = 311), were similar in age (p = 0.91), and presented with a larger comorbidity burden (3.3 +/- 1.3 vs 2.4 +/- 1.5, p < 0.001). The effect of advancing age (every 5 years) on mortality in the ESRD cohort (hazard ratio [HR] = 1.11, 95% confidence interval [CI] = 1.03-1.20) was less than in the non-ESRD cohort (HR = 1.28, 95% CI = 1.25-1.32). Similarly, the effect of each additional comorbidity in the ESRD cohort was less (HR = 1.04, 95% CI = 0.91-1.19) than in the non-ESRD group (HR = 1.20, 95% CI = 1.16-1.25). Lastly, ESRD was independently associated with a 3-fold greater hazard of mortality. CONCLUSIONS: Advancing age and increasing number of MCC have a differential effect on mortality risk in patients with ESRD compared with their non-ESRD counterparts. Future studies should focus on assessment of nonlinear relationships of age, MCC, and naturally occurring clusters of MCC on mortality. PMID- 26562309 TI - The Gut Balance Revolution by Gerard E Mullin, MD. PMID- 26562308 TI - Primary Care Clinicians' Perspectives on Reducing Low-Value Care in an Integrated Delivery System. AB - CONTEXT: Perceptions about low-value care (eg, medical tests and procedures that may be unnecessary and/or harmful) among clinicians with capitated salaries are unknown. OBJECTIVE: Explore clinicians' perceived use of and responsibility for reducing low-value care by focusing on barriers to use, awareness of the Choosing Wisely campaign, and response to reports of peer-comparison resource use and practice patterns. METHODS: Electronic, cross-sectional survey, distributed in 2013, to 304 salaried primary care physicians and physician assistants at Group Health Cooperative. MAIN OUTCOME MEASURES: Attitudes, awareness, and barriers of low-value care strategies and initiatives. RESULTS: A total of 189 clinicians responded (62% response rate). More than 90% believe cost is important to various stakeholders and believe it is fair to ask clinicians to be cost-conscious. Most found peer-comparison resource-use reports useful for understanding practice patterns and prompting peer discussions. Two-thirds of clinicians were aware of the Choosing Wisely campaign; among them, 97% considered it a legitimate information source. Although 88% reported being comfortable discussing low-value care with patients, 80% reported they would order tests or procedures when a patient insisted. As key barriers in reducing low-value care, clinicians identified time constraints (45%), overcoming patient preferences/values (44%), community standards (43%), fear of patients' dissatisfaction (41%), patients' knowledge about the harms of low-value care (38%), and availability of tools to support shared decision making (37%). CONCLUSIONS: Salaried clinicians are aware of rising health care costs and want to be stewards of limited health care resources. Evidence-based initiatives such as the Choosing Wisely campaign may help motivate clinicians to be conscientious stewards of limited health care resources. PMID- 26562310 TI - The darker-is-deeper heuristic for the perception of 3D shape from shading: Is it perceptually or ecologically valid? AB - The darker-is-deeper heuristic was originally proposed by Langer and Zucker (1994) for approximating 3D shape from shading under conditions of diffuse illumination that typically occur for outdoor scenes on a cloudy day, and it is based on the assumption that vignetting is the primary source of luminance variation under those conditions. It was later rejected as a model of human perception by Langer and Bulthoff (2000), because points in concavities that appear to be the deepest are most often located on local luminance maxima. Despite that result, this heuristic has continued to be described in the literature as a viable model of human perception (e.g., Chen & Tyler, 2015; Tyler, 1998), based entirely on the appearance of image intensity gratings, which have little or no connection to real 3D surfaces or patterns of illumination. In this article we will present a large number of examples to show what actually happens when surfaces are viewed under directional and diffuse illuminations. The results will highlight a number of well-known phenomena in addition to vignetting that can influence the pattern of shading on a surface under diffuse illumination, and they will also demonstrate that the darker-is-deeper heuristic is generally invalid for all types of illumination, except in unusual circumstances. PMID- 26562311 TI - Interference during eye movement preparation shifts the timing of perisaccadic compression. AB - Our perception of the surrounding environment remains stable despite the fact that we frequently change the retinal position of input by rapid gaze shifts (saccades). There is a long-standing debate whether visual stability depends on an active mechanism using an efference copy of the impending saccadic motor command. Behavioral studies showing changes in perception around the time of saccades are consistent with a predictive mechanism, but previous studies of perceptual effects in humans confounded saccade programming with the resulting physical eye movement. In three experiments, we used a saccadic inhibition (SI) paradigm to delay saccadic onset while participants were performing a perisaccadic localization task. As expected, the perceived position of the probe stimulus was systematically biased (compressed) toward the saccadic goal, already during the presaccadic interval. In the SI condition, the localization error was shifted in time, in line with it following saccade intention rather than execution. The pattern was not the consequence of the probe being captured by the timing of the flashed distractor, but depended instead on the delay in saccadic onset time caused by SI. Importantly, the same configurations of perceptual probes presented with a flashed backward mask when participants maintained fixation did not lead to similar localization errors as saccade trials. This pattern of results is consistent with an active, sensorimotor explanation for perisaccadic mislocalization and, more generally, theories emphasizing the role of motor prediction in visual stability. PMID- 26562313 TI - Electrophysiological responses of feedback processing are modulated by MAOA genotype in healthy male adolescents. AB - A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene is closely related to aggression. Although previous studies suggested that impaired ability of feedback processing might be associated with aggressive behaviour, studies concerning the MAOA gene-related aggression rarely focused on the link between MAOA gene and feedback processing. We therefore sought to investigate the effect of MAOA genotype on electrophysiological responses of feedback processing in 72 healthy male adolescents during a simple monetary gambling task. Feedback processing was investigated by measuring the feedback related negativity (FRN) and the P300 as electrophysiological markers. We observed a decreased electrophysiological response of the loss-gain difference waves from 250 to 350 ms (dFRN) in individuals with the lower activity alleles (MAOA-L) during the task, an effect that was driven primarily by the considerably altered response to monetary gains. The reduced dFRN in MAOA-L group might indicate poor ability to learn from feedback, which is followed by adjusting future behaviour. And MAOA-L carriers exhibited lower P300 compared with subjects with higher activity alleles (MAOA-H), which suggested fewer attentional resources were allocated to feedback processing. In addition, MAOA-L carriers demonstrated higher aggression and the aggression were inversely correlated with dFRN across two groups; further analyses suggested that dFRN mediated the MAOA genotype-aggression relationship. Consequently, we concluded that it might be the altered feedback processing that makes MAOA-L carriers more vulnerable to aggressive behaviour. PMID- 26562312 TI - Search for an Endogenous Bombesin-Like Receptor 3 (BRS-3) Ligand Using Parabiotic Mice. AB - Bombesin-like receptor 3 (BRS-3) is an X-linked G protein-coupled receptor involved in the regulation of energy homeostasis. Brs3 null (Brs3-/y) mice become obese. To date, no high affinity endogenous ligand has been identified. In an effort to detect a circulating endogenous BRS-3 ligand, we generated parabiotic pairs of mice between Brs3-/y and wild type (WT) mice or between WT controls. Successful parabiosis was demonstrated by circulatory dye exchange. The Brs3-/y WT and WT-WT pairs lost similar weight immediately after surgery. After 9 weeks on a high fat diet, the Brs3-/y-WT pairs weighed more than the WT-WT pairs. Within the Brs3-/y-WT pairs, the Brs3-/y mice had greater adiposity than the WT mice, but comparable lean and liver weights. Compared to WT mice in WT-WT pairs, Brs3-/y and WT mice in Brs3-/y-WT pairs each had greater lean mass, and the Brs3 /y mice also had greater adiposity. These results contrast to those reported for parabiotic pairs of leptin receptor null (Leprdb/db) and WT mice, where high leptin levels in the Leprdb/db mice cause the WT parabiotic partners to lose weight. Our data demonstrate that a circulating endogenous BRS-3 ligand, if present, is not sufficient to reduce adiposity in parabiotic partners of Brs3-/y mice. PMID- 26562314 TI - Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study. AB - We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. PMID- 26562315 TI - Notch1 Pathway Activity Determines the Regulatory Role of Cancer-Associated Fibroblasts in Melanoma Growth and Invasion. AB - Cancer-associated fibroblasts (CAF) play a crucial role in regulating cancer progression, yet the molecular determinant that governs the tumor regulatory role of CAF remains unknown. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in CAF. CAF carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors. PMID- 26562316 TI - Recombinant measles AIK-C vaccine strain expressing heterologous virus antigens. AB - Further attenuated measles vaccines were developed more than 50 years ago and have been used throughout the world. Recombinant measles vaccine candidates have been developed and express several heterologous virus protective antigens. Immunogenicity and protective actions were confirmed using experimental animals: transgenic mice, cotton rats, and primates. The recent development of measles vaccine-based vectored vaccine candidates has been reviewed and some information on recombinant measles vaccines expressing respiratory syncytial virus proteins has been shown and discussed. PMID- 26562317 TI - A sera-epidemiological study on pertussis immunity levels among community populations and an analysis of the underlying factors in Tianjin China. AB - BACKGROUND: The aim of this study is to characterize the sera-epidemiology of pertussis immunity levels among community populations and to identify the underlying factors. Moreover, our study will help resolve new issues encountered during the control and prevention of pertussis reemergence. METHODS: The anti pertussis antibody levels among community populations were examined using enzyme linked immunosorbent assays (ELISA) over three years. Comparative studies were carried out to assess the efficacy of different types of vaccines. Meanwhile, the duration of protection provided by DTaP within the under-7 age group was subjected to further analysis. RESULTS: The average positive rate for anti pertussis antibody was 49.15% across all community populations, among which the 4 12 age group showed a rate substantially lower than those of other groups (P<0.001). There was no statistically significant difference in anti-pertussis antibody levels (P=0.977) between people receiving three and four doses of the vaccine. The surveillance results showed that the positive antibody response rate elicited by component pertussis combo (DTcP) vaccines (84.44%) was strikingly higher than that elicited by acellular pertussis combo (DTaP) vaccines (37.22%, P<0.001). More specifically, when given 4 doses of DTcP vaccines, 66.67% of the people showed positive anti-pertussis toxin (PT) antibody levels, which was higher than the ratio of 9.87% (P<0.001) in the case of DTaP vaccines. The positive anti-pertussis antibody levels peaked at 73% within the first five months following vaccination and then gradually decreased to below 20% in four years. The positive rate was inversely correlated with the length of time after vaccination (r=-0.929, P=0.003). CONCLUSIONS: The anti-pertussis antibody levels were not only relatively low among community populations, but also dropped excessively rapidly among vaccinated populations. Natural infection is an important contributor to the high pertussis immunity levels seen in adolescents and adults. The efficacy of DTaP remains to be improved. PMID- 26562318 TI - Pertussis vaccines: WHO position paper, August 2015--Recommendations. AB - This article presents the World Health Organization's (WHO) recommendations for the use of vaccines against Bordetella pertussis from the WHO position paper on Pertussis vaccines: WHO position paper--August 2015, recently published in the Weekly Epidemiological Record (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2015;90(August(35)):433-60). This position paper summarizes the most recent developments in the field of pertussis disease and its prevention by vaccination. It includes the WHO position on the choice of Pertussis vaccine as well as on the use of additional strategies, particularly vaccination during pregnancy, for prevention of early infant mortality. This document replaces the first WHO position paper on vaccines against disease caused by Pertussis published in 2010 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2010;85(October(40)):385-400) and incorporates the revised guidance on the choice of pertussis vaccines published in July 2014 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2014;89(July(30)):337-44). Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2014 and April 2015 meetings. The evidence presented at the meetings can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. PMID- 26562319 TI - Identification of DLD, by immunoproteomic analysis and evaluation as a potential vaccine antigen against three Vibrio species in Epinephelus coioides. AB - Vibrio spp. represent a serious threat to the culture of Epinephelus coioides (Orange-spotted Grouper) in Southeast Asia. In this study we used two-dimensional electrophoresis (2-DE) and Western blotting to identify common immunogenic proteins of Vibrio alginolyticus, Vibrio harveyi and Vibrio parahaemolyticus. Membranes were probed with orange-spotted grouper anti-V. alginolyticus sera and accordingly 60, 58 and 48 immunogenic protein spots were detected. By matching analysis for the three Western blotting membranes, 6 cross immunogenic spots for the three Vibrio species were identified. They were Outer membrane protein W (OmpW), dihydrolipoamide dehydrogenase (DLD), succinate dehydrogenase flavoprotein subunit(SDHA), elongation factor Ts(Ts), peptide ABC transporter periplasmic peptide-binding protein and phosphoenolpyruvate carboxykinase(PEPCK). One of the proteins, DLD, was used to evaluate the cross protective function for E. coioides with a bacterial immunization and challenge method. The relative percent survival rate of E. coioides against V. alginolyticus, V. harveyi and V. parahaemolyticus was 90%, 86% and 80%, respectively. This work may provide potential cross protective vaccine candidate antigens for three Vibrio species, and DLD may be considered as an effective cross-protective immunogen against three Vibrio species. PMID- 26562320 TI - Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine. AB - FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (p<0.02). In macaques with the FH(high) baseline phenotype, the respective anti FHbp C4b deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. PMID- 26562322 TI - Combination therapies with daclatasvir and asunaprevir on NS3-D168 mutated HCV in human hepatocyte chimeric mice. AB - BACKGROUND: Although the frequency of emergent drug-resistant strains of HCV in patients who failed to respond to simeprevir plus pegylated interferon (PEG-IFN) and ribavirin (RBV) decreased after cessation of the treatment, it is not clear whether or not the NS3-D168 variants affect the outcome of NS5A and NS3 inhibitor combination therapy. In this study, we investigated the relationship between the effect of daclatasvir plus asunaprevir treatment and the frequencies of NS3-D168 variants. METHODS: HCV genotype-1b-infected human hepatocyte chimeric mice with various frequencies of NS3-D168 amino acid substitutions were treated with asunaprevir alone or in combination with daclatasvir for 4 weeks. Frequencies of NS3-D168 substitutions at baseline were analysed by ultra-deep sequencing. Some mice with NS3-D168 substitutions were treated with PEG-IFN or telaprevir for 4 weeks. RESULTS: Mice with high frequencies of NS3-D168 showed low susceptibility to asunaprevir treatment and failed to respond to daclatasvir plus asunaprevir therapy. In contrast, mice with a low frequency (less than approximately 14%) of NS3-D168 showed a similar susceptibility to wild-type HCV-infected mice and achieved viral eradication with daclatasvir plus asunaprevir therapy. Although treatment with either telaprevir or PEG-IFN resulted in reduction of serum HCV RNA levels, no significant decrease in the frequency of NS3-D168 substitutions was achieved. CONCLUSIONS: Daclatasvir and asunaprevir treatment could eliminate NS3-D168 variant HCV if the frequency was low. It is necessary to confirm that the frequency of NS3-D168 variants has decreased sufficiently before adopting daclatasvir plus asunaprevir therapy in patients with simeprevir plus PEG-IFN/RBV treatment failure. PMID- 26562321 TI - Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease. AB - BACKGROUND: The moderate level of protection conferred by influenza vaccines is well-known, but the vaccine's ability to attenuate symptom severity among vaccinated individuals (i.e., vaccine failures) has not been established. METHODS: We enrolled otherwise healthy adults who presented with influenza-like illness (ILI) at five US military hospitals between 2009 and 2014. Influenza was diagnosed and subtyped by PCR. Individual and composite severity scores were compared between those who had vs. had not received the seasonal influenza vaccine >14 days prior to enrollment. RESULTS: A total of 155 cases of influenza (A/H1N1, n=69; A/H3N2, n=66; A/untyped, n=3; B, n=17) were identified, of whom 111 (72%; A/H1N1, n=44; A/H3N2, n=52; A/untyped, n=3; B, n=12) had been vaccinated. Women were significantly less likely to be vaccinated than men (49% vs. 89%; p<0.01). In multivariate analysis, vaccinated individuals were significantly less likely to report a fever >101 degrees F (OR 0.24; 95% CI [0.10, 0.62]) and more likely to report myalgias (OR 3.31; 95% CI [1.22, 8.97]) than vaccinated individuals. Among patients with A/H3N2 infection, upper respiratory and total symptom severity scores were significantly lower for vaccinated patients during the first 2 days of illness, and differences in total symptom severity persisted over 7 days (p<0.05 for all comparisons). Differences across additional symptom categories (lower respiratory and systemic) were also observed throughout 7 days of illness in bivariate analyses. Differences in symptom severity were not observed between vaccinated and unvaccinated participants with A/H1N1 infection. CONCLUSIONS: Among patients with A/H3N2 infection, receipt of seasonal influenza vaccine was associated with reduced symptom severity. Patient-centered discussion about the benefits of influenza vaccination should be expanded to include the possibility that the vaccine could attenuate symptoms. PMID- 26562323 TI - Three-Dimensional Platelet-Rich Plasma Hydrogel Model to Study Early Tendon Healing. AB - Since the experimental conditions of cell cultures may bias results, it is critical to use suitable models. This is also true in the context of tendon cell biology and the study of platelet-rich plasma (PRP) therapies and PRP-augmented cell-based therapies. We compared the culture of human tendon cells in 2 dimensions (2D) with PRP-supplemented media to culture in matching 3-dimensional (3D) PRP hydrogels. Cell proliferation, cell shape, and the pattern of gene and protein expression were examined. Our data revealed modifications in cell shape and enhanced expression of tenomodulin and scleraxis in 3D hydrogels. Additionally, protein secretion analysis using glass-based arrays specific for angiogenesis revealed differences in interleukin (IL)-6 and IL-8 protein expression between 2D cultures and 3D hydrogels, while the secretion of other angiogenic or inflammatory cytokines was unaffected. Our study suggests that 3D hydrogels are physiologically more relevant than 2D cultures in the study of tendon cells, based on cell shape, support of tenocyte proliferation, phenotype, and the pattern of gene and protein expression. PMID- 26562324 TI - Using nonlinear least squares to assess relative expression and its uncertainty in real-time qPCR studies. AB - Relative expression ratios are commonly estimated in real-time qPCR studies by comparing the quantification cycle for the target gene with that for a reference gene in the treatment samples, normalized to the same quantities determined for a control sample. For the "standard curve" design, where data are obtained for all four of these at several dilutions, nonlinear least squares can be used to assess the amplification efficiencies (AE) and the adjusted DeltaDeltaCq and its uncertainty, with automatic inclusion of the effect of uncertainty in the AEs. An algorithm is illustrated for the KaleidaGraph program. PMID- 26562325 TI - Cadmium affects mitotically inherited histone modification pathways in mouse embryonic stem cells. AB - The fetal basis of adult disease (FeBAD) theorizes that embryonic challenges initiate pathologies in adult life through epigenetic modification of gene expression. In addition, inheritance of H3K27 methylation marks, especially in vitro, is still controversial. Metals, such as Cd, are known to affect differentiation, DNA repair and epigenetic status in mES cells. We tested the premise that Cd exerts differential toxicity in mouse embryonic stem (mES) cells by targeting total histone protein (THP) production early in stem cell development, while affecting H3K27-mono-methylation (H3K27me(1)) in latter stages of differentiation. The inability of mES cells to recover from Cd insult at concentrations greater than IC50 indicates that maximum cytotoxicity occurs during initial hours of exposure. Moreover, as a measure of chromatin stability, low dose acute Cd exposure lowers THP production. The heritable effects of Cd exposure on cell proliferation, chromatin stability and transcription observed through several cell population doublings were detected only during alternate passages on days 3, 7, and 11, presumably due to slower maturation of histone methylation marks. These findings demonstrate a selective disruption of chromatin structure following acute Cd exposure, an effect not seen in developmentally mature cells. Hence, we present that acute Cd toxicity is cumulative and disrupts DNA repair, while concurrently affecting cell cycle progression, chromatin stability and transcriptional state in mES cells. PMID- 26562326 TI - Combination of mTOR Inhibitors Augments Potency while Activating PI3K Signaling in Pituitary Tumors. AB - BACKGROUND: Despite the success in treating some cancers, the efficacy of the mTOR inhibitors rapalogs as anti-cancer therapeutics has been limited. AIMS: We undertook to examine the effects of Torin1, a second-generation selective ATP competitive mTOR inhibitor, in non-functioning pituitary tumor cells. During characterization of the molecular mechanisms that mediate Torin1 actions, there seemed to be a rationale for combining it with rapalogs. METHODS: Proliferation assays, flow cytometry and Western blotting were applied to assess the effects of Torin1, RAD001 and their combination on an MtT/E pituitary cell line and human derived non-functioning pituitary tumor cells. RESULTS: Combined long treatments of Torin1 and RAD001 induced a pronounced reduction in cell growth and viability of both MtT/E pituitary cells and human-derived non-functioning pituitary tumor cells, superior to each drug alone. This was remarkable in the 10 nM combination and was reflected in a triggered decrease of cyclin D3 and p21/CIP expression. Interestingly, Akt-Thr308 and SIN1-Thr86 phosphorylations were robustly elevated in the combined treatment, accompanied by a reduction in PTEN expression. Phosphorylation of p70S6K was abolished in all individual and combined treatments. Akt-Ser473 phosphorylation, induced by RAD001, was reduced by the combined treatment to the same extent as when treated by Torin1 alone. CONCLUSIONS: Our results suggest that the differential signaling mechanisms induced by these compounds eventually converge to lead to an efficient blockade of the PI3K/Akt/mTOR pathway in pituitary tumor cells and may facilitate a reduction in treatment dosage. PMID- 26562327 TI - Self-focused attention affects subsequent processing of positive (but not negative) performance appraisals. AB - BACKGROUND AND OBJECTIVES: Cognitive-behavioral models highlight the conjoint roles of self-focused attention (SFA), post-event processing (PEP), and performance appraisals in the maintenance of social anxiety. SFA, PEP, and biased performance appraisals are related to social anxiety; however, limited research has examined how SFA affects information-processing following social events. The current study examined whether SFA affects the relationships between performance appraisals and PEP following a social event.. METHODS: 137 participants with high (n = 72) or low (n = 65) social anxiety were randomly assigned to conditions of high SFA or low SFA while engaging in a standardized social performance. Subsequent performance appraisals and PEP were measured. RESULTS: Immediate performance appraisals were not affected by SFA. High levels of SFA led to a stronger, inverse relationship between immediate positive performance appraisals and subsequent negative PEP. High levels of SFA also led to a stronger, inverse relationship between negative PEP and changes in positive performance appraisals.. LIMITATIONS: Future research should examine whether the current findings, which involved a standardized social performance event, extend to interaction events as well as in a clinical sample. CONCLUSIONS: These findings suggest that SFA affects the processing of positive information following a social performance event. SFA is particularly important for understanding how negative PEP undermines positive performance appraisals.. PMID- 26562328 TI - Treatment of Depression in Patients with Concomitant Cardiac Disease. AB - Depressed patients are at increased risk of cardiovascular (CV) disease (CVD) and those with concomitant depression and CVD are at increased risk of death. The safety and efficacy of antidepressants in patients with CVD varies greatly between the agent used and type of disease. This review will summarize the CV adverse effect and drug interaction profile of antidepressants and discuss the use of antidepressants in CVD patients. We searched MEDLINE, PubMed, CINAHL, Web of Science, PsycINFO, and The Cochrane Library from inception to June 2014 to identify studies relevant to antidepressant use in patients with CVD. Primary references from the identified articles were also evaluated for inclusion. Descriptive analysis was performed for the included studies in this review. Orthostatic hypotension was more common with tricyclic antidepressants (TCAs), trazodone and monoamine oxidase inhibitors (MAOIs). Hypertension can be significant with serotonin norepinephrine reuptake inhibitors (SNRIs) and MAOIs. The potential for QT prolongation is present with TCAs, certain selective serotonin reuptake inhibitors (SSRIs), certain SNRIs and mirtazapine. Due to its low risk of drug-drug interactions, adverse effect profile and potential for beneficial antiplatelet activity, sertraline could be considered the choice antidepressant for patients with ischemic heart disease. SSRIs and potentially SNRIs are relatively safe and effective options for patients with heart failure. In patients at high risk for ventricular arrhythmias, bupropion has the overall lowest risk for QT prolongation. TCAs and MAOIs should be avoided in patients with concomitant CVD. In conclusion, due to the increased morbidity and mortality associated with comorbid CVD and depression, practitioners should readily assess and initiate management of depression in such patients. The choice of antidepressant should take into account the potential CV impact of the various agents balancing safety and efficacy. PMID- 26562329 TI - Electrochemical acetylcholinesterase biosensor based on ZnO nanocuboids modified platinum electrode for the detection of carbosulfan in rice. AB - The consumption of carbosulfan-contaminated rice affects the immune and lymphocyte response, germinal centers in the spleen, plasma cells in popliteal lymphoid nodes, bone marrow cells and granulocyte-macrophage progenitor cells. Towards this, a highly sensitive acetylcholinesterase (AChE) cyclic voltammetric biosensor based on zinc oxide (ZnO) nanocuboids modified platinum (Pt) electrode has been successfully developed. The Pt/ZnO/AChE/Chitosan bio-electrode was employed for the electrochemical detection of carbosulfan in rice sample. Under optimum conditions, the Pt/ZnO/AChE/Chitosan bio-electrode detected carbosulfan ranging from 5 to 30 nM with a detection limit (LOD) of 0.24 nM. The developed Pt/ZnO/AChE/Chitosan bio-electrode showed good recovery (99.06-100.96%), thus providing a promising tool for analysis of carbosulfan in rice sample. PMID- 26562330 TI - Femtomolar level detection of RASSF1A tumor suppressor gene methylation by electrochemical nano-genosensor based on Fe3O4/TMC/Au nanocomposite and PT modified electrode. AB - The alterations in DNA methylation pattern have been identified as one of the most frequent molecular phenomenon in human cancers. The RASSF1A tumor suppressor gene was shown to be often inactivated by hypermethylation of its promoter region. In the present study, a novel chip format sandwich electrochemical genosensor has been developed for the analysis of gene-specific methylation using Fe3O4/N-trimethyl chitosan/gold (Fe3O4/TMC/Au) nanocomposite as tracing tag to label DNA probe and polythiophene (PT) as immobilization platform of sensing element. However, no attempt has yet been made to conjugate DNA probe to Fe3O4/TMC/Au nanocomposite as electrochemical label for strip-based genosensing. Cyclic voltammetric (CV) analysis indicated that modification procedure was well performed. Differential pulse voltammetry (DPV) was employed for quantitative assessment of RASSF1A DNA promoter methylation. The electrochemical measurements accomplished using non-specific DNA fragments mixed with samples, revealed the high specificity and selectivity in methylation analysis by means of this DNA nanobiosensor. With the linear range of concentration from 1 * 10(-14)M to 5 * 10(-9)M and the detection limit of 2 * 10(-15)M, this new strategy has shown such a promising application to be used for universal analysis of any DNA sequence. PMID- 26562331 TI - Ultrasensitive non-enzymatic immunosensor for carcino-embryonic antigen based on palladium hybrid vanadium pentoxide/multiwalled carbon nanotubes. AB - A novel and sensitive sandwich-type non-enzymatic electrochemical immunosensor was fabricated for quantitative monitoring of carcino-embryonic antigen (CEA). Nanocomposite of stannic oxide/reduced graphene oxide was used as substrate material to increase the specific surface area and enhance the conductivity of the glassy carbon electrode. Gold nanoparticles (Au NPs) were introduced to link substrate materials and primary antibodies (Ab1) and accelerate the electron transfer in this system. At the same time, the palladium nanoparticles (Pd NPs) vanadium pentoxide (V2O5)/multiwalled carbon nanotubes (MWCNTs) were used as the label of secondary antibodies (Ab2). This composite label has shown excellent catalytic activity towards the reduction of H2O2. The nanomaterial-based signal amplification can improve the sensitivity and lower the limit of detection. The proposed immunosensor showed wide linear range from 0.5 pgmL(-1) to 25 ngmL(-1) with limit of detection of 0.17 pgmL(-1). This novel immunosensor was used to analyze serum sample. The results indicated that this immunosensor may find huge potential application for quantitative detection of CEA in the clinical diagnosis. PMID- 26562332 TI - The body and objects represented in the ventral stream of the parieto-premotor network. AB - The network between the parietal cortex and premotor cortex has a pivotal role in sensory-motor control. Grasping-related neurons in the anterior intraparietal area (AIP) and the ventral premotor cortex (F5) showed complementary properties each other. The object information for grasping is sent from the parietal cortex to the premotor cortex for sensory-motor transformation, and the backward signal from the premotor cortex to parietal cortex can be considered an efference copy/corollary discharge that is used to predict sensory outcome during motor behavior. Mirror neurons that represent both own action and other's action are involved in this system. This system also very well fits with body schema that reflects online state of the body during motor execution. We speculate that the parieto-premotor network, which includes the mirror neuron system, is key for mapping one's own body and the bodies of others. This means that the neuronal substrates that control one's own action and the mirror neuron system are shared with the "who" system, which is related to the recognition of action contribution, i.e., sense of agency. Representation of own and other's body in the parieto-premotor network is key to link between sensory-motor control and higher-order cognitive functions. PMID- 26562333 TI - Body representations in the human brain revealed by kinesthetic illusions and their essential contributions to motor control and corporeal awareness. AB - The human brain can generate a continuously changing postural model of our body. Somatic (proprioceptive) signals from skeletal muscles and joints contribute to the formation of the body representation. Recent neuroimaging studies of proprioceptive bodily illusions have elucidated the importance of three brain systems (motor network, specialized parietal systems, right inferior fronto parietal network) in the formation of the human body representation. The motor network, especially the primary motor cortex, processes afferent input from skeletal muscles. Such information may contribute to the formation of kinematic/dynamic postural models of limbs, thereby enabling fast online feedback control. Distinct parietal regions appear to play specialized roles in the transformation/integration of information across different coordinate systems, which may subserve the adaptability and flexibility of the body representation. Finally, the right inferior fronto-parietal network, connected by the inferior branch of the superior longitudinal fasciculus, is consistently recruited when an individual experiences various types of bodily illusions and its possible roles relate to corporeal awareness, which is likely elicited through a series of neuronal processes of monitoring and accumulating bodily information and updating the body representation. Because this network is also recruited when identifying one's own features, the network activity could be a neuronal basis for self consciousness. PMID- 26562334 TI - Modeling the motor cortex: Optimality, recurrent neural networks, and spatial dynamics. AB - Specialization of motor function in the frontal lobe was first discovered in the seminal experiments by Fritsch and Hitzig and subsequently by Ferrier in the 19th century. It is, however, ironical that the functional and computational role of the motor cortex still remains unresolved. A computational understanding of the motor cortex equals to understanding what movement variables the motor neurons represent (movement representation problem) and how such movement variables are computed through the interaction with anatomically connected areas (neural computation problem). Electrophysiological experiments in the 20th century demonstrated that the neural activities in motor cortex correlated with a number of motor-related and cognitive variables, thereby igniting the controversy over movement representations in motor cortex. Despite substantial experimental efforts, the overwhelming complexity found in neural activities has impeded our understanding of how movements are represented in the motor cortex. Recent progresses in computational modeling have rekindled this controversy in the 21st century. Here, I review the recent developments in computational models of the motor cortex, with a focus on optimality models, recurrent neural network models and spatial dynamics models. Although individual models provide consistent pictures within their domains, our current understanding about functions of the motor cortex is still fragmented. PMID- 26562335 TI - Hereditary sensory and autonomic neuropathy types 4 and 5: Review and proposal of a new rehabilitation method. AB - Although pain is unpleasant, it should serve as a reminder for individuals to avoid similar damaging incidents in the future. Hereditary sensory and autonomic neuropathy (HSAN) includes genetic disorders involving various sensory and autonomic dysfunctions. They are classified by the mode of inheritance, clinical features, and related genes. HSAN type 4 (HSAN-4) and type 5 (HSAN-5) are characterized by insensitivity to pain and thermal sensation. Further, HSAN-4 is accompanied by decreased sweating and intellectual disabilities. These characteristics of HSAN-4 and -5 result in many clinical features, such as pediatric, psychiatric, orthopedic, oral, dermatological, and ophthalmological problems. Orthopedic problems include destructive injuries such as multiple fractures and joint dislocation. Studies on gait have shown greater speed and higher heel contact angular velocity in HSAN-4 and -5 patients compared with controls. Studies on grasp-lift-holding tasks have shown higher grasp force and fluctuations in acceleration of the object. We believe that these findings represent outcomes of deficient motor learning. We propose a new rehabilitation method for patients with HSAN-4 and -5, with the aim of decreasing their destructive injuries. PMID- 26562338 TI - Nitrate removal from polluted water by using a vegetated floating system. AB - Nitrate (NO3(-)) water pollution is one of the most prevailing and relevant ecological issues. For instance, the wide presence of this pollutant in the environment is dramatically altering the quality of superficial and underground waters. Therefore, we set up a floating bed vegetated with a terrestrial herbaceous species (Italian ryegrass) with the aim to remediate hydroponic solutions polluted with NO3(-). The floating bed allowed the plants to grow and achieve an adequate development. Ryegrass was not affected by the treatments. On the contrary, plant biomass production and total nitrogen content (N-K) increased proportionally to the amount of NO3(-) applied. Regarding to the water cleaning experiments, the vegetated floating beds permitted to remove almost completely all the NO3(-) added from the hydroponic solutions with an initial concentration of 50, 100 and 150 mg L(-1). Furthermore, the calculation of the bioconcentration factor (BCF) indicated this species as successfully applicable for the remediation of solutions polluted by NO3(-). In conclusion, the results highlight that the combination of ryegrass and the floating bed system resulted to be effective in the remediation of aqueous solutions polluted by NO3(-). PMID- 26562339 TI - The leaching behavior of cyclophosphamide and ifosfamide from soil in the presence of co-contaminant--Mixture sorption approach. AB - Anticancer drugs (ACDs) exhibit high biological activity, they are cytotoxic, genotoxic, and are constantly released into the environment as a result of incomplete metabolism. Consequently they pose a serious threat to the environment and human health due to their carcinogenic, mutagenic and/or reproductive toxicity properties. Knowledge of their bioavailability, including their sorption to soils and their impact on the soil-groundwater pathway, is crucial for their risk assessment. Laboratory batch and column leaching tests are important tools for determining the release potential of contaminants from soil or waste material. Batch and column tests were carried out with soils differing in physicochemical properties, each spiked with cyclophosphamide (CK) or ifosfamide (IF). Moreover, due to the fact that environmental pollutants may occur as coexisting compounds in the soil the mobility evaluation for ACDs in the mixture with metoprolol (MET; beta-blocker) as a co-contaminant was performed. In order to assess appropriateness, the batch and column tests were compared. The release depended on the properties of both the soil and the presence of co-contaminants. The faster release was observed for coarse-grained soil with the smallest organic matter content (MS soil: 90% decrease in concentration until liquid-to-solid ratio (L/S) of 0.3 L kg(-1) for all tests' layout) than for loamy sand (LS soil: 90% decrease in concentration until ratio L/S of 0.75 L kg(-1)). ACDs are highly mobile in soil systems. Furthermore, the decrease of mobility of ifosfamide was observed with the presence of a co-contaminant (metoprolol) in both of the soils (in MS soil a decrease of 29%; in LS soil a decrease of 26%). The mobility of cyclophosphamide does not depend on the presence of a contaminant for MS soil, but also exhibits a decrease of 21% in LS soil. PMID- 26562340 TI - The seasonal dynamics of the stream sources and input flow paths of water and nitrogen of an Austrian headwater agricultural catchment. AB - Our study examines the source aquifers and stream inputs of the seasonal water and nitrogen dynamics of a headwater agricultural catchment to determine the dominant driving forces for the seasonal dynamics in the surface water nitrogen loads and concentrations. We found that the alternating aquifer contributions throughout the year of the deep and shallow aquifers were the main cause for the seasonality of the nitrate concentration. The deep aquifer water typically contributed 75% of the total outlet discharge in the summer and 50% in the winter when the shallow aquifer recharges due to low crop evapotranspiration. The shallow aquifer supplied the vast majority of the nitrogen load to the stream due to the significantly higher total nitrogen concentration (11 mg-N/l) compared to the deep aquifer (0.50 mg-N/l). The main stream input pathway for the shallow aquifer nitrogen load was from the perennial tile drainages providing 60% of the total load to the stream outlet, while only providing 26% of the total flow volume. The diffuse groundwater input to the stream was the largest input to the stream (39%), but only supplied 27% to the total nitrogen load as the diffuse water was mostly composed of deep aquifer water. PMID- 26562337 TI - Vascular endothelial growth factor A: just one of multiple mechanisms for sex specific vascular development within the testis? AB - Testis development from an indifferent gonad is a critical step in embryogenesis. A hallmark of testis differentiation is sex-specific vascularization that occurs as endothelial cells migrate from the adjacent mesonephros into the testis to surround Sertoli-germ cell aggregates and induce seminiferous cord formation. Many in vitro experiments have demonstrated that vascular endothelial growth factor A (VEGFA) is a critical regulator of this process. Both inhibitors to VEGFA signal transduction and excess VEGFA isoforms in testis organ cultures impaired vascular development and seminiferous cord formation. However, in vivo models using mice which selectively eliminated all VEGFA isoforms: in Sertoli and germ cells (pDmrt1-Cre;Vegfa(-/-)); Sertoli and Leydig cells (Amhr2-Cre;Vegfa(-/ )) or Sertoli cells (Amh-Cre;Vegfa(-/-) and Sry-Cre;Vegfa(-/-)) displayed testes with observably normal cords and vasculature at postnatal day 0 and onwards. Embryonic testis development may be delayed in these mice; however, the postnatal data indicate that VEGFA isoforms secreted from Sertoli, Leydig or germ cells are not required for testis morphogenesis within the mouse. A Vegfa signal transduction array was employed on postnatal testes from Sry-Cre;Vegfa(-/-) versus controls. Ptgs1 (Cox1) was the only upregulated gene (fivefold). COX1 stimulates angiogenesis and upregulates, VEGFA, Prostaglandin E2 (PGE2) and PGD2. Thus, other gene pathways may compensate for VEGFA loss, similar to multiple independent mechanisms to maintain SOX9 expression. Multiple independent mechanism that induce vascular development in the testis may contribute to and safeguard the sex-specific vasculature development responsible for inducing seminiferous cord formation, thus ensuring appropriate testis morphogenesis in the male. PMID- 26562341 TI - Dispersion of TSP and PM(10) emissions from quarries in complex terrain. AB - This study evaluates AERMOD and CALPUFF dispersion calculations of particulate matter emissions from stone quarries in two mountainous regions against TSP and PM10 measurements, using both observational and WRF-modeled meteorological data. Due to different model parameterization, AERMOD dispersion predictions were in better agreement with the measured concentrations than those obtained by CALPUFF. As expected, the smaller the distance between the meteorological station, the source (quarry) and the receptors, the better the predictions of both AERMOD and CALPUFF. In contrast, using in-situ wind field obtained by runs of the WRF meteorological model for the complex terrain study area provided, in general, less accurate dispersion estimates than when using (even remote) meteorological observations. In particular, using the three-dimensional WRF-modeled wind field within CALPUFF did not provide any advantage over using the two-dimensional wind field, which is the common procedure of AERMOD and CALPUFF. Dry deposition was more significant for ambient concentration estimation in AERMOD than in CALPUFF. PMID- 26562342 TI - Influence of the water quality improvement on fish population in the Seine River (Paris, France) over the 1990-2013 period. AB - Over the past 20 years, rules concerning wastewater treatment and quality of water discharged into the environment have changed considerably. Huge investments have been made in Paris conurbation to improve waste water treatment processes in accordance with the European Water Framework Directive. The interdepartmental association for sewage disposal in Paris conurbation (SIAAP) carried out a monitoring of both fish assemblages and water quality in the Seine River around the Paris conurbation (France) since the early 90's. The main goal of this study was to estimate the influence of the water quality improvement on fish. On one hand, the study confirmed the improvement of the water quality (dissolved oxygen, ammonia nitrogen, organic matter) in the Seine River, mostly focused downstream of Paris conurbation. On the other hand, an increase of the number of species occurred from 1990 (14) to 2013 (21). Moreover, changes in the river Seine assemblages happened over that 23-year period with emergence of sensitive species (ruffe, scalpin and pike-perch). The improvement of the water quality was also reported with respect to the Index of Biotic Integrity (IBI). However, no variation of pollutant concentrations in roach, eel and chub muscles has been observed. An exceedance of the environmental quality standards have even been reported all over this period as regards mercury and organochlorine. PMID- 26562343 TI - Separate treatment of hospital and urban wastewaters: A real scale comparison of effluents and their effect on microbial communities. AB - Hospital wastewaters (HWW) contain wider spectrum and higher quantity of pharmaceuticals than urban wastewaters (UWW), but they are generally discharged in sewers without pretreatment. Since traditional urban wastewater treatment plants (WWTP) are not designed to treat HWWs, treated effluents may still contain pollutants that could impair receiving aquatic environments. Hence, a better understanding of the effect of pharmaceuticals in the environment is required. Biofilms are effective "biological sensors" for assessing the environmental effects of pharmaceuticals due to their ability to respond rapidly to physical, chemical and biological fluctuations by changes in their structure and composition. This study evaluated the efficiency of biological treatment with conventional activated sludge system performed parallel on HWW and UWW. Furthermore, six successive monthly colonizations of biofilms were done on autoclaved stones, placed in grid-baskets in the hospital treated effluents (HTE) and urban treated effluents (UTE). The biomass of these biofilms as well as the structure and diversity of their bacterial communities were investigated. Results showed better treatment efficiency for phosphate and nitrite/nitrate during the treatment of UWW. Pharmaceuticals from all investigated therapeutic classes (beta blockers, nonsteroidal anti-inflammatory drugs, antibiotics, analgesics and anticonvulsants) were efficiently removed, except for carbamazepine. The removal efficiency of the antibiotics, NSAIDs and beta-blockers was higher during the treatment of HWW. HTE and UTE shaped the bacterial communities in different ways. Higher concentrations of pharmaceuticals in the HTE caused adapted development of the microbial community, leading to less developed biomass and lower bacterial diversity. Seasonal changes in solar irradiance and temperature, caused changes in the community composition of biofilms in both effluents. According to the removal efficiency of pharmaceuticals, the separate treatment was beneficial. However, their high concentrations in the HTE and the following adaptations of biofilm communities identify the importance of adapting wastewater treatment to specific hospital pollutants. PMID- 26562344 TI - Enteric and indicator virus removal by surface flow wetlands. AB - We investigated the occurrence and attenuation of several human enteric viruses (i.e., norovirus, adenovirus, Aichi virus 1, polyomaviruses, and enterovirus) as well as a plant virus, pepper mild mottle virus (PMMoV), at two surface flow wetlands in Arizona. The retention time in one of the wetlands was seven days, whereas in the other wetland it could not be defined. Water samples were collected at the inlet and outlet from the wetlands over nine months, and concentration of viral genomes was determined by quantitative polymerase chain reaction (qPCR). Of the human enteric viruses tested, adenovirus and Aichi virus 1 were found in the greatest prevalence in treated wastewater (i.e., inlet of the wetlands). Reduction efficiencies of enteric viruses by the wetlands ranged from 1 to 3 log10. Polyomaviruses were generally removed to below detection limit, indicating at least 2 to 4 log10 removal. PMMoV was detected in a greater concentration in the inlet of both wetlands for all the viruses tested (10(4) to 10(7) genome copies/L), but exhibited little or no removal (1 log10 or less). To determine the factors associated with virus genome attenuation (as determined by qPCR), the persistence of PMMoV and poliovirus type 1 (an enterovirus) was studied in autoclaved and natural wetland water, and deionized water incubated under three different temperatures for 21 days. A combination of elevated water temperature and biological activities reduced poliovirus by 1 to 4 log10, while PMMoV was not significantly reduced during this time period. Overall, PMMoV showed much greater persistence than human viruses in the wetland treatment. PMID- 26562345 TI - Predictors of ICU Admission in Patients With Cancer and the Related Characteristics and Outcomes: A 5-Year Registry-Based Study. AB - OBJECTIVE: To identify factors predictive of admission of patients with cancer to an ICU. In addition, the study aimed to describe the characteristics and outcomes, both short-term and long-term, of patients with cancer admitted to the ICU. DESIGN: Retrospective case-control study, utilizing the institution's cancer registry. SETTING: Comprehensive cancer center. PATIENTS: Patients with cancer. The case group consisted of patients who required ICU admission during the study period, whereas the control group consisted of patients who did not require ICU admission. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The patient characteristics and outcomes were recorded. Univariate and multivariate analyses were conducted to determine factors associated with ICU admission. The registry included 10,792 patients, and among those, 2,439 patients (22.6%) required ICU admission after a median of 10.1 months (interquartile range, 3.28-25.2). The following factors were associated with ICU admission: hematologic malignancy (odds ratio, 1.51; 95% CI, 1.26-1.81), chemotherapy (odds ratio, 1.74; 95% CI, 1.48-2.03), advanced cancer (odds ratio, 2.57; 95% CI, 1.44-4.60), and smoking (odds ratio, 1.38; 95% CI, 1.20-1.61). The most common ICU admission diagnoses were sepsis (21.5%) and respiratory insufficiency/failure (25.7%). The ICU mortality was 36.5%, whereas the 1-year and 5-year survival rates were 22.8% and 14.2%, respectively. CONCLUSION: In a comprehensive cancer center, about one fourth of the patients required ICU admission. Addressing modifiable risk factors associated with ICU admission is essential to potentially reduce ICU admissions and improve long-term survival. PMID- 26562346 TI - Urinary Output Predicts Survival in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiovascular Surgery. AB - OBJECTIVES: Extracorporeal membrane oxygenation represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, survival remains poor and accurate risk stratification challenging. Therefore, we evaluated the predictive value of urinary output within 24 hours after extracorporeal membrane oxygenation initiation on mortality in patients undergoing venoarterial extracorporeal membrane oxygenation support following cardiovascular surgery and aimed to improve established risk prediction models. DESIGN: Single-center, observational registry. SETTING: University-affiliated tertiary care center. PATIENTS: We included 205 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following cardiovascular surgery at a university-affiliated tertiary-care center into our single-centre registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a median follow-up time of 35 months (interquartile range, 19-69), 64% of patients died. Twenty-four-hour urinary output was the strongest predictor of outcome among renal function variables with an adjusted hazard ratio per 1 SD of 0.55 (95% CI, 0.40-0.76; p < 0.001) for 30 day mortality and of 0.65 (95% CI, 0.53-0.86; p = 0.002) for 2-year long-term mortality. Most remarkably, 24-hour urinary output showed additional prognostic value beyond that achievable with the simplified acute physiology score-3 and sequential organ failure assessment score indicated by improvements in the category-free net reclassification index for 30-day mortality (simplified acute physiology score-3: 36%, p = 0.015; sequential organ failure assessment score: 36%, p = 0.02), as well as for 2-year mortality (simplified acute physiology score-3: 33%, p = 0.02; sequential organ failure assessment score: 43%, p = 0.005). CONCLUSIONS: We identified 24-hour urinary output as a strong and easily available predictor of mortality in patients undergoing extracorporeal membrane oxygenation therapy following cardiovascular surgery. Implementation of 24-hour urinary output leads to a substantial improvement of established risk prediction models in this vulnerable patient population. These results are particularly compelling because measurement of urinary output is inexpensive and routinely performed in all critical care units. PMID- 26562347 TI - Effectiveness and Clinical Outcomes of a Two-Step Implementation of Conservative Oxygenation Targets in Critically Ill Patients: A Before and After Trial. AB - OBJECTIVES: Conservative oxygen therapy is aimed at the prevention of harm by iatrogenic hyperoxia while preserving adequate tissue oxygenation. Our aim was to study the effectiveness and clinical outcomes of a two-step implementation of conservative oxygenation targets in the ICU. DESIGN: This was a before and after stepwise implementation study of conservative oxygenation targets, between July 2011 and July 2014. The primary endpoint was the proportion of PaO2 values within the target range. Secondary outcomes included ventilator-free days at day 28, length of stay, and mortality. SETTING: Three closed-format ICUs in the Netherlands. PATIENTS: We analyzed data on 15,045 eligible admissions. INTERVENTIONS: The first implementation phase consisted of providing training and feedback on new guidelines instructing for explicit targets for arterial oxygen tension (PaO2, 55-86 mm Hg) and oxyhemoglobin saturation (SpO2, 92-95%). In the second phase, bedside clinicians were additionally assisted in guideline adherence by a computerized decision-support system. MEASUREMENTS AND MAIN RESULTS: The proportion of PaO2 in the target range increased from 47% at baseline to 63% in phase 1 and to 68% in phase 2 (p < 0.0001). Episodes of hyperoxia decreased (p < 0.0001), whereas hypoxic episodes remained unchanged (p = 0.06) during the study. Mechanical ventilation time was significantly lower (p < 0.01) during both study phases. After adjustment for potential confounders, ventilator-free days in phase 1 and phase 2 were higher than baseline: adjusted mean difference, 0.55 (95% CI, 0.25-0.84) and 0.48 (95% CI, 0.11-0.86), respectively. Adjusted ICU mortality and ICU-free days did not significantly differ between study phases. Hospital mortality decreased in reference to baseline: adjusted odds ratio, 0.84 (95% CI, 0.74-0.96) for phase 1 and 0.82 (95% CI, 0.69-0.96) for phase 2. CONCLUSIONS: Stepwise implementation of conservative oxygenation targets was feasible, effective, and seemed safe in critically ill patients. The implementation was associated with several changes in clinical outcomes, but the causal impact of conservative oxygenation is still to be determined. PMID- 26562349 TI - Progress toward regional measles elimination - worldwide, 2000-2014. AB - In 2000, the United Nations General Assembly adopted the Millennium Development Goals (MDG), with MDG4 being a two-thirds reduction in child mortality by 2015, and with measles vaccination coverage being one of the three indicators of progress toward this goal.* In 2010, the World Health Assembly established three milestones for measles control by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) for children aged 1 year to >=90% nationally and >=80% in every district; 2) reduce global annual measles incidence to fewer than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).? In 2012, the World Health Assembly endorsed the Global Vaccine Action PlanS with the objective to eliminate measles in four World Health Organization (WHO) regions by 2015. WHO member states in all six WHO regions have adopted measles elimination goals. This report updates the 2000-2013 report (2) and describes progress toward global control and regional measles elimination during 2000-2014. During this period, annual reported measles incidence declined 73% worldwide, from 146 to 40 cases per million population, and annual estimated measles deaths declined 79%, from 546,800 to 114,900. However, progress toward the 2015 milestones and elimination goals has slowed markedly since 2010. To resume progress toward milestones and goals for measles elimination, a review of current strategies and challenges to improving program performance is needed, and countries and their partners need to raise the visibility of measles elimination, address barriers to measles vaccination, and make substantial and sustained additional investments in strengthening health systems. PMID- 26562350 TI - Hospital Characteristics and the Agency for Healthcare Research and Quality Inpatient Quality Indicators: A Systematic Review. AB - BACKGROUND: The Agency for Healthcare Research and Quality Inpatient Quality Indicators (IQIs) include inpatient mortality for selected procedures and medical conditions. They have assumed an increasingly prominent role in hospital comparisons. Healthcare delivery and policy-related decisions need to be driven by reliable research that shows associations between hospital characteristics and quality of inpatient care delivered. OBJECTIVES: To systematically review the literature on associations between hospital characteristics and IQIs. METHODS: We systematically searched PubMed and gray literature (2000-2012) for studies relevant to 14 hospital characteristics and 17 IQIs. We extracted data for study characteristics, IQIs analyzed, and hospital characteristics (e.g., teaching status, bed size, patient volume, rural vs. urban location, and nurse staffing). RESULTS: We included 16 studies, which showed few significant associations. Four hospital characteristics (higher hospital volume, higher nurse staffing, urban vs. rural status, and higher hospital financial resources) had statistically significant associations with lower mortality and selected IQIs in approximately half of the studies. For example, there were no associations between nurse staffing and four IQIs; however, approximately 50% of studies showed a statistically significant relationship between nurse staffing and lower mortality for six IQIs. For two hospital characteristics-higher bed size and disproportionate share percentage-all statistically significant associations had higher mortality. Five hospital characteristics (teaching status, system affiliation, ownership, minority-serving hospitals, and electronic health record status) had some studies with significantly positive and some with significantly negative associations, and many studies with no association. CONCLUSIONS: We found few associations between hospital characteristics and mortality IQIs. Differences in study methodology, coding across hospitals, and hospital case-mix adjustment may partly explain these results. Ongoing research will evaluate potential mechanisms for the identified associations. PMID- 26562351 TI - Reliability of Isometric and Eccentric Isokinetic Shoulder External Rotation. AB - CONTEXT: Shoulder external rotators are challenged eccentrically throughout the deceleration phase of throwing, which is thought to contribute to overuse injuries. To evaluate the effectiveness of intervention programs, as well as identifying deficits, reliable and responsive measures of isometric and eccentric shoulder external rotation are necessary. Previously, isometric measures have primarily tested a single position, and eccentric measures have not been found to have high reliability. OBJECTIVE: To examine the between-days reliability of multiple-angle isometric and dynamic eccentric isokinetic testing of shoulder external rotation. DESIGN: Repeated measures. PARTICIPANTS: 10 healthy subjects (age 30 +/- 12 y, height 166 +/- 13 cm, mass 72 +/- 10 kg). MAIN OUTCOME MEASURES: Average isometric peak torque of shoulder external rotation at 7 angles was measured. From these values, the angle of isometric peak torque was calculated. Dynamic eccentric average peak torque, average total work, and average angle of peak torque were measured. RESULTS: Between-days reliability was high for average peak torque during isometric contractions at all angles (ICC >= .85), as it was for dynamic eccentric average peak torque (ICC >= .97). The estimated angle of isometric peak torque (ICC <= .65) was not highly reliable between days. The average angle of peak torque from the eccentric testing produced inconsistent results. Average total work of dynamic eccentric shoulder external rotation was found to be highly reliable between days (ICC >= .97). CONCLUSION: Aspects of force such as peak torque and total work in isometric and eccentric testing of the shoulder external-rotator muscles can be measured reliably between days and used to objectively evaluate shoulder strength and identify changes when they occur. Angle measurements of peak torque could provide insight into the mechanical properties of the posterior shoulder muscles but were found to be inconsistent between days. PMID- 26562352 TI - Nacre-nanomimetics: Strong, Stiff, and Plastic. AB - The bricks and mortar in the classic structure of nacre have characteristic geometry, aspect ratios and relative proportions; these key parameters can be retained while scaling down the absolute length scale by more than 1 order of magnitude. The results shed light on fundamental scaling behavior and provide new opportunities for high performance, yet ductile, lightweight nanocomposites. Reproducing the toughening mechanisms of nacre at smaller length scales allows a greater volume of interface per unit volume while simultaneously increasing the intrinsic properties of the inorganic constituents. Layer-by-layer (LbL) assembly of poly(sodium 4-styrenesulfonate) (PSS) polyelectrolyte and well-defined [Mg2Al(OH)6]CO3.nH2O layered double hydroxide (LDH) platelets produces a dense, oriented, high inorganic content (~90 wt %) nanostructure resembling natural nacre, but at a shorter length scale. The smaller building blocks enable the (self-) assembly of a higher quality nanostructure than conventional mimics, leading to improved mechanical properties, matching those of natural nacre, while allowing for substantial plastic deformation. Both strain hardening and crack deflection mechanisms were observed in situ by scanning electron microscopy (SEM) during nanoindentation. The best properties emerge from an ordered nanostructure, generated using regular platelets, with narrow size dispersion. PMID- 26562353 TI - Structure and Thermal Expansion of Calcium-Thorium Apatite, [Ca4]F[Ca2Th4]T[(SiO4)6]O2. AB - Thorium silicate apatite with the formula [Ca3.84Th0.16]F[Ca2.79Th3.21]T(SiO4)6O2 . x(H) was synthesized by solid-state reaction, and its structure refined in P63/m from powder X-ray diffraction (XRD) data using the Rietveld method (a = 9.50172(9) A, c = 6.98302(8) A, V = 545.98(1) A(3); R-Bragg = 2.102%). It was found that thorium partitions strongly to the tunnel (T) 6h position rather than the framework (F) 4f site. Fourier transform infrared spectroscopy revealed only SiO4 tetrahedron, with SiO5 and SiO6 groups, sometimes observed in siliceous apatites absent, at least to the limit of detection of this technique. Thermal expansion of the thorium apatite determined by high-temperature XRD from 298-1173 K found Deltaa (0.87%) dilation to exceed Deltac (0.73%) with increasing temperature consistent with other silicate apatites. PMID- 26562354 TI - Promoting Photosensitivity and Detectivity of the Bi/Si Heterojunction Photodetector by Inserting a WS2 Layer. AB - Layered transition metal dichalcogenides (TMDs) have been proven to be essential building blocks for the high-performance optoelectronic devices as a result of their favorable bandgaps, extraordinary light absorption, and closed surface electronic structures. However, the in-depth exploration of their operating mechanism as insertion layers in heterojunction photodetectors is scarce. Here, we demonstrate that a Bi/Si heterojunction photodetector can achieve a superior performance by inserting a WS2 layer. A high photosensitivity of 1.4 * 10(8) cm(2)/W and an outstanding detectivity of 1.36 * 10(13) cm Hz(1/2) W(-1) are obtained, which are comparable or even surpass those of state-of-art commercial photodetectors. The working mechanism of the Bi/WS2/Si sandwich-structured photodetector is unveiled, including the efficient passivation of the interface, enhancement of light absorption, and selective carrier blocking. Finally, a good voltage tunability of the photoresponse is also demonstrated. These findings are significant to the deep understanding on the integration of layered TMDs with conventional semiconductors, and they provide an attractive methodology to develop layered TMDs in a multi-junction system. PMID- 26562355 TI - Dearomative Indole (3 + 2) Reactions with Azaoxyallyl Cations--New Method for the Synthesis of Pyrroloindolines. AB - Herein, we report the first examples of the synthesis of pyrroloindolines by means of (3 + 2) dearomative annulation reactions between 3-substituted indoles and highly reactive azaoxyallyl cations. Computational studies using density functional theory (DFT) (B3LYP-D3/6-311G**++) support a stepwise reaction pathway in which initial C-C bond formation takes place at C3 of indole, followed by ring closure to give the observed products. Insights gleaned from these calculations indicate that the solvent, either TFE or HFIP, can stabilize the transition state through H-bonding interactions with oxygen of the azaoxyallyl cation and other relevant intermediates, thereby increasing the rates of these reactions. PMID- 26562356 TI - Copper-Mediated Remote C-H Bond Chalcogenation of Quinolines on the C5 Position. AB - An efficient and convenient method is developed for the remote C-H bond chalcogenation of 8-aminoquinoline scaffolds on the C5 position that is geometrically inaccessible. The protocol makes use of inexpensive CuBr2 as mediator and shows good tolerance toward numerous disulfides/diselenides and aliphatic amides, giving the corresponding products in good to excellent yield. PMID- 26562358 TI - Total Synthesis of Solandelactone I. AB - Since the marine natural products solandelactones A-I were isolated from the hydroid Solanderia secunda and investigated by Seo et al. in 1996, considerable synthetic efforts toward these marine oxylipins followed. However, the structure elucidation of solandelactone I remained incomplete, and no synthesis has been reported. On the basis of our retrosynthetic analysis, the key building blocks were combined in a Horner-Wadsworth-Emmons reaction to create two common intermediates for the stereodivergent synthesis of all four diastereomers 1-4 matching the proposed structure of solandelactone I. Comparison of the published analytical data of natural product solandelactone I and data obtained from the synthetic endeavor toward diastereomers 1-4 enabled the structure assignment of isomer 3; the proposed biosynthetic pathway for marine oxylipins also supports the result. PMID- 26562357 TI - A novel approach to inhibit bone resorption: exosite inhibitors against cathepsin K. AB - BACKGROUND AND PURPOSE: Cathepsin K (CatK) is a major drug target for the treatment of osteoporosis. Potent active site-directed inhibitors have been developed and showed variable success in clinical trials. These inhibitors block the entire activity of CatK and thus may interfere with other pathways. The present study investigates the antiresorptive effect of an exosite inhibitor that selectively inhibits only the therapeutically relevant collagenase activity of CatK. EXPERIMENTAL APPROACH: Human osteoclasts and fibroblasts were used to analyse the effect of the exosite inhibitor, ortho-dihydrotanshinone (DHT1), and the active site inhibitor, odanacatib (ODN), on bone resorption and TGF-beta1 degradation. Cell cultures, Western blot, light and scanning electron microscopy as well as energy dispersive X-ray spectroscopy, molecular modelling and enzymatic assays were used to evaluate the inhibitors. KEY RESULTS: DHT1 selectively inhibited the collagenase activity of CatK, without affecting the viability of osteoclasts. Both inhibitors abolished the formation of resorption trenches, with DHT1 having a slightly higher IC50 value than ODN. Maximal reductions of other resorption parameters by DHT1 and ODN were comparable, respectively 41% and 33% for total resorption surface, 46% and 48% for resorption depths, and 83% and 61% for C-terminal telopetide fragment (CTX) release. DHT1 did not affect the turnover of fibrosis-associated TGF-beta1 in fibroblasts, whereas 500 nM ODN was inhibitory. CONCLUSIONS AND IMPLICATIONS: Our study shows that an exosite inhibitor of CatK can specifically block bone resorption without interfering with other pathways. PMID- 26562359 TI - Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte. AB - Calcium (Ca(2+)) plays many important regulatory roles in cardiac muscle cells. In the initial phase of the action potential, influx of Ca(2+) through sarcolemmal voltage-gated L-type Ca(2+) channels (LCCs) acts as a feed-forward signal that triggers a large release of Ca(2+) from the junctional sarcoplasmic reticulum (SR). This Ca(2+) drives heart muscle contraction and pumping of blood in a process known as excitation-contraction coupling (ECC). Triggered and released Ca(2+) also feed back to inactivate LCCs, attenuating the triggered Ca(2+) signal once release has been achieved. The process of ECC consumes large amounts of ATP. It is now clear that in a process known as excitation-energetics coupling, Ca(2+) signals exert beat-to-beat regulation of mitochondrial ATP production that closely couples energy production with demand. This occurs through transport of Ca(2+) into mitochondria, where it regulates enzymes of the tricarboxylic acid cycle. In excitation-signaling coupling, Ca(2+) activates a number of signaling pathways in a feed-forward manner. Through effects on their target proteins, these interconnected pathways regulate Ca(2+) signals in complex ways to control electrical excitability and contractility of heart muscle. In a process known as excitation-transcription coupling, Ca(2+) acting primarily through signal transduction pathways also regulates the process of gene transcription. Because of these diverse and complex roles, experimentally based mechanistic computational models are proving to be very useful for understanding Ca(2+) signaling in the cardiac myocyte. PMID- 26562360 TI - Hyperckemia unmasking celiac disease in a patient with myasthenia gravis. PMID- 26562361 TI - Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in grey wolves. AB - In an era of ever-increasing amounts of whole-genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array-based genome scans is uncertain. We previously performed a SNP array-based genome scan to identify candidate genes under selection in six distinct grey wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1-kb nongenic neutral regions, and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to noncandidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in sweed and bayenv analyses, respectively. This result verifies the use of genomewide SNP surveys to tag genes that contain functional variants between populations. We highlight nonsynonymous variants in APOB, LIPG and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genomewide genotyping arrays with large-scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations. PMID- 26562362 TI - Effect of the Hydrogen Bond on Photochemical Synthesis of Silver Nanoparticles. AB - The effect of a hydrogen bond on the photochemical synthesis of silver nanoparticles has been investigated via experimental and theoretical methods. In a benzophenone system, the photochemical synthesis process includes two steps, which are that hydrogen abstraction reaction and the following reduction reaction. We found that for the first step, an intermolecular hydrogen bond enhances the proton transfer. The efficiency of hydrogen abstraction increases with the hydrogen bond strength. For the second step, the hydrogen-bonded ketyl radical complex shows higher reducibility than the ketyl radical. The inductively coupled plasma-optical emission spectroscopy (ICP-OES) measurement exhibits a 2.49 times higher yield of silver nanoparticles in the hydrogen bond ketyl radical complex system than that for the ketyl radical system. Theoretical calculations show that the hydrogen bond accelerates electron transfer from the ketyl radical to the silver ion by raising the SOMO energy of the ketyl radical; thus, the SOMO-LUMO interaction is more favorable. PMID- 26562363 TI - Detecting a dexmedetomidine-evoked reduction of noradrenaline release in the human brain with the alpha2C-adrenoceptor PET ligand [11C]ORM-13070. AB - PET imaging can for some neurotransmitters be used to measure synaptic neurotransmitter concentrations. The objective of this study was to test whether the receptor binding of the alpha2C -AR antagonist PET tracer [(11)C]ORM-13070 would increase in response to reductions in synaptic noradrenaline, evoked by dexmedetomidine as a sympatholytic drug challenge. Six subjects underwent a control PET scan and two dexmedetomidine PET scans. Dexmedetomidine was infused with target plasma concentrations of 0.6 and 0.2 ng/ml. Tracer binding was measured by voxel-based analysis of bound per free (B/F) images. ROI-based analysis was performed in the dorsal striatum and in the thalamus. Vital signs and drug concentrations in plasma were measured and the sedative effect was estimated with the visual analog scale. In the voxel-based analysis, dexmedetomidine administration was associated with a tendency to increased B/F tracer in the right thalamus (mean, +17%, P = 0.14, and +19%, P = 0.05, with the low and high dose, respectively). Tracer binding in the dorsal striatum was unaffected by dexmedetomidine. A cluster with significantly increased B/F tracer (+42%, P = 0.01) was seen in the right superior temporal gyrus with low-dose dexmedetomidine, but not after the high dose. Brain uptake of [(11)C]ORM-13070 has previously been shown to be reduced in conditions of increased synaptic noradrenaline concentrations. In this study, tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, but statistical significance was not reached. PMID- 26562364 TI - Single-Cell Mechanics Provides an Effective Means To Probe in Vivo Interactions between Alveolar Macrophages and Silver Nanoparticles. AB - Single-cell mechanics, derived from atomic force microscopy-based technology, provides a new and effective means to investigate nanomaterial-cell interactions upon in vivo exposure. Lung macrophages represent initial and important responses upon introducing nanoparticles into the respiratory tract, as well as particle clearance with time. Cellular mechanics has previously proven effective to probe in vitro nanomaterial-cell interactions. This study extends technology further to probe the interactions between primary alveolar macrophages (AM) and silver nanoparticles (AgNPs) upon in vivo exposure. Two types of AgNPs, 20 and 110 nm, were instilled to rat lung at 0.5 mg AgNPs/kg body weight, and allowed 24 h interaction. The consequences of these interactions were investigated by harvesting the primary AMs while maintaining their biological status. Cellular mechanics measurements revealed the diverse responses among AM cells, due to variations in AgNP uptake and oxidative dissolving into Ag(+). Three major responses are evident: zero to low uptake that does not alter cellular mechanics, intracellular accumulation of AgNPs trigger cytoskeleton rearrangement resulting in the stiffening of mechanics, and damage of cytoskeleton that softens the mechanical profile. These effects were confirmed using confocal imaging of F actin and measurements of reactive oxygen species production. More detailed intracellular interactions will also be discussed on the basis of this study in conjunction with prior knowledge of AgNP toxicity. PMID- 26562365 TI - Using Scanning-Probe Block Copolymer Lithography and Electron Microscopy To Track Shape Evolution in Multimetallic Nanoclusters. AB - Here we describe a general method for synthesizing multimetallic core-shell nanoclusters on surfaces. By patterning seeds at predesignated locations using scanning-probe block copolymer lithography, we can track shape evolution in nanoclusters and elucidate their growth pathways using electron microscopy. The growth of core-shell nanostructures on surface-bound seeds is a highly anisotropic process and often results in multimetallic anisotropic nanostructures. The shell grows at specific edge and corner sites of the patterned seeds and propagates predominately from the top hemisphere of the seeds. PMID- 26562366 TI - Time-Resolved Nucleic Acid Hybridization Beacons Utilizing Unimolecular and Toehold-Mediated Strand Displacement Designs. AB - Nucleic acid hybridization probes are sought after for numerous assay and imaging applications. These probes are often limited by the properties of fluorescent dyes, prompting the development of new probes where dyes are paired with novel or nontraditional luminescent materials. Luminescent terbium complexes are an example of such a material, and these complexes offer several unique spectroscopic advantages. Here, we demonstrate two nonstem-loop designs for light up nucleic acid hybridization beacons that utilize time-resolved Forster resonance energy transfer (TR-FRET) between a luminescent Lumi4-Tb cryptate (Tb) donor and a fluorescent reporter dye, where time-resolved emission from the dye provides an analytical signal. Both designs are based on probe oligonucleotides that are labeled at their opposite termini with Tb and a fluorescent reporter dye. In one design, a probe is partially blocked with a quencher dye-labeled oligonucleotide, and target hybridization is signaled through toehold-mediated strand displacement and loss of a competitive FRET pathway. In the other design, the intrinsic folding properties of an unblocked probe are utilized in combination with a temporal mechanism for signaling target hybridization. This temporal mechanism is based on a recently elucidated "sweet spot" for TR-FRET measurements and exploits distance control over FRET efficiencies to shift the Tb lifetime within or outside the time-gated detection window for measurements. Both the blocked and unblocked beacons offer nanomolar (femtomole) detection limits, response times on the order of minutes, multiplexing through the use of different reporter dyes, and detection in complex matrices such as serum and blood. The blocked beacons offer better mismatch selectivity, whereas the unblocked beacons are simpler in design. The temporal mechanism of signaling utilized with the unblocked beacons also plays a significant role with the blocked beacons and represents a new and effective strategy for developing FRET probes for bioassays. PMID- 26562367 TI - Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge. AB - OBJECTIVE: To determine the half-life of serum caffeine concentrations and its relation to apnea of prematurity (AOP) after caffeine is discontinued in preparation for hospital discharge. STUDY DESIGN: Prospective cohort study involving preterm infants with gestational ages ?33 weeks at birth. After caffeine was discontinued, serum caffeine concentrations and electronic detection of pathologic apnea, defined a priori, were obtained at 24 and 168 h, respectively. RESULT: Caffeine levels decreased from 13.3+/-3.8 to 4.3+/-2 mg l( 1) (n=50, mean+/-s.d.) at 24 and 168 h, respectively (P<0.01). The mean caffeine half-life was 87+/-25 h at 35+/-1 weeks postmenstrual age. Seven days after discontinuation of caffeine, 64% of the infants had pathologic apnea. CONCLUSION: Hospital discharge planning for preterm infants with a history of AOP should be carefully considered after discontinuing caffeine. This study showed that caffeine may not reach subtherapeutic levels until around 11-12 days. PMID- 26562368 TI - C-reactive protein levels following hepatitis B vaccine in healthy newborns. AB - OBJECTIVE: Evaluate the effect of Hepatitis B vaccine (HepB) on C-reactive protein (CRP) levels in healthy term infants. STUDY DESIGN: A prospective controlled study in an academic medical center serving an inner city community. Subjects were singleton, term and late pre-term infants delivered vaginally with normal physical examination and without risk factors for or signs of sepsis. CRP levels were measured in cord blood and at the time of newborn genetic screening. The early HepB group received HepB within a few hours after birth. The late HepB group had HepB delayed until after the repeat CRP. RESULT: One hundred and eighty two infants were enrolled (94 early HepB, 88 late HepB) with similar demographic features in each group. Neither the mean cord CRP (early HepB, 0.24+/-0.23 vs late HepB, 0.30+/-0.68 mg l(-1), P=0.37) nor the median of the repeat CRP (early HepB, 2.6 (interquartile range, 1.18 to 7.03) vs late HepB, 1.7 (interquartile range, 0.73 to 5.8) mg l(-1), P=0.14) showed significant differences between the two groups. CONCLUSION: HepB does not affect CRP levels in healthy term infants. PMID- 26562369 TI - The complete blood cell count in a refined cohort of preterm NEC: the importance of gestational age and day of diagnosis when using the CBC to estimate mortality. AB - OBJECTIVE: The value of the white blood cell count (WBC) in necrotizing enterocolitis (NEC) is controversial. One reason for this confusion may be that the various WBC lineages change substantially with increasing gestational age and thereby age of NEC onset. This study postulated that if a data set was large enough and the diagnosis of NEC clean enough, absolute WBC counts would facilitate prediction of NEC mortality. The objective of this study was to determine whether absolute WBC counts enhance the prediction of NEC mortality. STUDY DESIGN: A de-identified data subset from the Pediatrix national data set specific to the diagnoses of NEC in patients who had a CBC drawn on the day of diagnosis (exclusive of the diagnoses of spontaneous intestinal perforations and congenital anomalies) was the target for analysis. Values of primary interest included: gestation, day of diagnosis, absolute WBC count, platelet count, hematocrit, mortality and the day of diagnosis. Stepwise regression analysis was used to predict mortality. RESULT: A total of 4059 (79%) survivors and 1107 (21%) infants who died with a diagnosis of medical or surgical NEC were included in the data set. Associations with mortality were found with low gestational age, low platelet count, low hematocrit, high band/segmented neutrophil ratio, earlier day of diagnosis, high birth weight z-score, non-white race, no antenatal steroids in gestations above 24 weeks, absolute lymphocyte count adjusted for gestational age, and absolute monocyte count high and low values. A stepwise regression analysis yielded a receiver-operator curve of 0.819 with a sensitivity of 65% and specificity of 84%. CONCLUSION: Absolute WBC values enhance prediction of NEC survival when used in combination with readily available data on the day of NEC diagnosis. PMID- 26562371 TI - Identification of severe gestational diabetes mellitus after new criteria used in China. AB - OBJECTIVE: To evaluate the way to identify severe gestational diabetes mellitus (GDM) according to the Ministry of Health (MOH) criteria associated with high risk of adverse pregnancy outcomes. STUDY DESIGN: Medical records of 9803 pregnant women attending Peking University First Hospital were analyzed retrospectively. Participants diagnosed as GDM were divided into different groups according to the different number of oral glucose tolerance test (OGTT) results and the prepregnancy body mass index (BMI). Participants without GDM were included in group N. The incidence of adverse pregnancy outcomes was analyzed according to incremental differences in prepregnancy BMI and the number of abnormal OGTT result. RESULT: (1) There were 21.8% (2133/9803) women diagnosed as GDM. (2) The frequency of large for gestational age in group 2 (GDM with 2 or more abnormal OGTT value; 21.6%) was significantly higher than group 1 (GDM with only 1 abnormal OGTT value; 16.8%) and group N (13.2%), and there was also significant difference between group 1 and group N. (3) Risk of adverse pregnancy outcomes in GDM would be increased in women with prepregnancy body mass index ?24 kg m(-2) in GDM. (4) Women with BMI <24 kg m(-2) in group 1 have low risk of adverse pregnancy outcomes and seldom need insulin (1.3%) in pregnancy. (5) There were 1142 cases (53.5%) of severe GDM in this study and 991 cases (46.5%) of mild GDM. CONCLUSION: GDM women with ?2 abnormal OGTT values or only 1 abnormal OGTT value but with prepregnancy BMI ?24 kg m(-2) should be recognized as severe GDM. We should pay more attention to and treat selectively with the severe GDM, especially in rural areas. PMID- 26562370 TI - Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet. AB - OBJECTIVE: Human milk is the best form of nutrition for preterm infants and has been associated with a lower incidence of necrotizing enterocolitis (NEC). Infants that develop NEC have a higher incidence of feeding intolerance and longer hospitalizations. The combination of a donor milk bank and donor milk derived fortifier has changed feeding practices in neonatal intensive care units (NICU). The purpose of this study is to assess the benefits and cost of an exclusive human milk (EHM) diet in very low birth weight (VLBW) infants in a community level III NICU. STUDY DESIGN: This is a retrospective study including preterm infants ?28 weeks and/or VLBW (?1500 g) who were enrolled from March 2009 until March 2014. Infants were grouped as follows: group H (entirely human milk based, born March 2012 to 2014), group B (bovine-based fortifier and maternal milk, born March 2009 to 2012), group M (mixed combination of maternal milk, bovine-based fortifier and formula, born March 2009 to 2012) and group F (formula fed infants, born March 2009 to 2012). Baseline characteristics among the four groups were similar. RESULT: The study included 293 infants between gestational ages 23 to 34 weeks and birth weights between 490 and 1700 g. Feeding intolerance occurred less often (P<0.0001), number of days to full feeds was lower (P<0.001), incidence of NEC was lower (P<0.011), and total hospitalization costs were lower by up to $106,968 per infant (P<0.004) in those fed an EHM diet compared with the other groups. Average weight gain per day was similar among the four groups (18.5 to 20.6 g per day). CONCLUSIONS: Implementing an EHM diet in our VLBW infants has led to a significant decrease in the incidence of NEC. Other benefits of this diet include: decreased feeding intolerance, shorter time to full feeds, shorter length of stay, and lower hospital and physician charges for extremely premature and VLBW infants. PMID- 26562372 TI - Successful primary use of VVDL+V ECMO with cephalic drain in neonatal respiratory failure. AB - OBJECTIVE: To describe the use of double-lumen venovenous (VVDL) extracorporeal membrane oxygenation (ECMO) with cephalic draining cannula (VVDL+V) as a primary approach for all neonatal respiratory diagnoses and to compare our single-center experience with data as collected in the Extracorporeal Life Support Organization (ELSO) database. STUDY DESIGN: We retrospectively reviewed all cases of ECMO for neonatal respiratory failure performed in the neonatal intensive-care unit at a large referral children's hospital, the Children's Healthcare of Atlanta at Egleston (CHOA-E). Comparisons were then made to neonatal respiratory ECMO data retrieved from the ELSO database. RESULTS: At CHOA-E 162 of 189 cases were completed with the VVDL+V approach. Survival in the VVDL+V cohort was 89.1% versus 68.7% from ELSO, P<0.001. For those complications considered, the overall risk of complication favored the CHOA-E VVDL+V group as compared with ELSO (odds ratio (OR) 0.71 (0.52-0.7)) as did the risk of neurologic complications (OR 0.29, (0.15-0.58)), including intracranial hemorrhage (OR 0.39 (0.18-0.97), P=0.011). CONCLUSION: The VVDL+V approach can be used successfully as the primary approach for ECMO for neonatal respiratory failure of various etiologies and in this single-center cohort this approach was associated with improved survival and lower rates of complication as compared with the ELSO database. PMID- 26562373 TI - Effects of hyperthyroidism on hand grip strength and function. AB - Hyperthyroidism is a pathologic condition in which the body is exposed to excessive amounts of circulating thyroid hormones. Skeletal muscle is one of the major target organs of thyroid hormones. We evaluated hand grip strength and function in patients with overt hyperthyroidism. Fifty-one patients newly diagnosed with hyperthyroidism and 44 healthy controls participated in this study. Age, height, weight, and dominant hand of all participants were recorded. The diagnosis of hyperthyroidism was confirmed by clinical examination and laboratory tests. Hand grip strength was tested at the dominant hand with a Jamar hand dynamometer. The grooved pegboard test (PGT) was used to evaluate hand dexterity. The Duruoz Hand Index (DHI) was used to assess hand function. No significant differences were found in terms of clinical and demographic findings between the patients with hyperthyroidism and healthy controls (p > 0.05). Significant differences were found between the patients with hyperthyroidism and healthy controls regarding PGT and DHI scores (p < 0.05). Hyperthyroidism seemed to affect hand dexterity and function more than hand grip strength and seemed to be associated with reduced physical function more than muscle strength. This may also indicate that patients with hyperthyroidism should be evaluated by multidisplinary modalities. PMID- 26562374 TI - Pressure ulcer-related harm: beyond root cause analysis. PMID- 26562375 TI - Pressure ulcer prevalence and prevention practices: a cross-sectional comparative survey in Norway and Ireland. AB - OBJECTIVE: This study explored whether the risk assessment method, structured versus clinical judgment, influences pressure ulcer (PU) prevalence or prevention strategies. METHOD: A cross section survey design was employed with use of a pre designed data collection instrument. Following ethical approval and consent, data was gathered from two acute care settings, one in Norway (clinical judgment) and one in Ireland (structured risk assessment using the Maelor Score). RESULTS: Data were obtained from 180 patients, 59 in Norway and 121 in Ireland. Of the patients 48% were male and 49% were female, gender was not recorded for 3%. The most common age bracket was 70-99 years of age, 46% of the study population. PU prevalence was 54% in the Norwegian site with the majority of PUs (69%) being category 1, and 12% in the Irish site with the majority (50%) being category 2. Only 8% of patients in the Norwegian site were risk assessed on admission compared with 85% in the Irish site. No dynamic mattresses and four pressure redistribution cushions were in use in the Norwegian site, whereas, in the Irish site, 27 dynamic mattresses and 11 pressure redistribution cushions were used, the majority (44%) for high-risk individuals. Of those at risk of PU development, 15% in the Norwegian site and 56% in the Irish site had a documented repositioning care plan when in bed, and 0% in the Norwegian site and 13% in the Irish site for when seated on a chair. CONCLUSION: There were inconsistencies in approach to PU risk assessment and prevention across the two clinical settings. However, prevalence rates differed, mainly relating to category 1 PU damage. Even though formal risk assessment is well established in the Irish site, this is not necessarily followed up with appropriated PU prevention. Thus, the method of risk assessment does not seem to influence subsequent care planning, questioning the role of formal risk assessment; however, despite this, risk assessment does put a focus on an important clinical problem. In the Norwegian site, a lack of risk assessment and appropriate equipment may be a confounding factor worthy of further exploration. PMID- 26562376 TI - Clinical effectiveness of a silicone foam dressing for the prevention of heel pressure ulcers in critically ill patients: Border II Trial. AB - OBJECTIVE: Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU). METHOD: A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial. RESULTS: Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs. CONCLUSION: We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi layer soft silicone foam dressings for PU prevention in the ICU. PMID- 26562377 TI - Microcirculatory responses of sacral tissue in healthy individuals and inpatients on different pressure-redistribution mattresses. AB - OBJECTIVE: The aim of this study was to explore the interaction between interface pressure, pressure-induced vasodilation, and reactive hyperaemia with different pressure-redistribution mattresses. METHOD: A cross-sectional study was performed with a convenience sample of healthy young individuals, and healthy older individuals and inpatients, at a university hospital in Sweden. Blood flow was measured at depths of 1mm, 2mm, and 10mm using laser Doppler flowmetry and photoplethysmography. The blood flow, interface pressure and skin temperature were measured in the sacral tissue before, during, and after load while lying on one standard hospital mattress and three different pressure-redistribution mattresses. RESULTS: There were significant differences between the average sacral pressure, peak sacral pressure, and local probe pressure on the three pressure-redistribution mattresses, the lowest values found were with the visco elastic foam/air mattress (23.5 +/- 2.5mmHg, 49.3 +/- 11.1mmHg, 29.2 +/- 14.0mmHg, respectively). Blood flow, measured as pressure-induced vasodilation, was most affected in the visco-elastic foam/air group compared to the alternating pressure mattress group at tissue depths of 2mm (39.0% and 20.0%, respectively), and 10mm (56.9 % and 35.1%, respectively). Subjects in all three groups, including healthy 18-65 year olds, were identified with no pressure-induced vasodilation or reactive hyperaemia on any mattress (n=11), which is considered a high-risk blood flow response. CONCLUSION: Interface pressure magnitudes considered not harmful during pressure-exposure on different pressure redistribution mattresses can affect the microcirculation in different tissue structures. Despite having the lowest pressure values compared with the other mattresses, the visco-elastic foam/air mattress had the highest proportion of subjects with decreased blood flow. Healthy young individuals were identified with the high-risk blood flow response, suggesting an innate vulnerability to pressure exposure. Furthermore, the evaluation of pressure-redistribution support surfaces in terms of mean blood flow during and after tissue exposure is not feasible, but assessment of pressure-induced vasodilation and reactive hyperaemia could be a new way to assess individualised physiological measurements of mechanisms known to be related to pressure ulcer development. PMID- 26562378 TI - Pressure ulcer prevention and healing using alternating pressure mattress at home: the PARESTRY project. AB - OBJECTIVE: Specialised pressure-relieving supports reduce or relieve the interface pressure between the skin and the support surface. The comparative effectiveness of dynamic support surfaces is debated. The aim of this study is to examine the impact of using an alternating pressure air mattress (APAM) on pressure ulcer (PU) incidence in patients receiving home-based care. A second aim was to determine the level of patient/family satisfaction with comfort and gain the views of the care team that used the APAM. METHOD: The PARESTRY study was a prospective observational study conducted in patients with a high risk of PUs (Braden score <15), discharged to hospital-care at home. The primary prevention groups consisted of patients with no PU at baseline who were in bed for at least 20 hours a day. Patients at baseline with a category 3 or 4 PU or a category 1 or 2 PU in association with poor general health or end-of-life status were included in the secondary prevention group. All patients were laid on an APAM. The primary end point was the % of patients with a worsening skin condition in the pressure area (heel, sacrum, ischium) at day 90 or at the end of the study. The primary analysis was done on the full analysis set (patients included with at least a second assessment), using the last observation carried forward technique to handle missing data, at day 90. A 95% confidence interval was calculated. RESULTS: Analysis was performed on 92 patients (30 in primary prevention and 62 in secondary prevention). The average time spent in bed was 22.7 (SD 2.7) hours a day and 22.6 (SD 2.2) hours in the primary and secondary prevention groups, respectively. At baseline, in the secondary group, 77% of patients had a sacral PU, 63% a heel PU, 8% an ischial tuberosity PU and 45% a PU in another area, a number of patients having multiple PUs. In the primary prevention group, 63% (19/30) of patients dropped out of the study (5 were hospitalised, 9 died, 5 other causes). In the secondary prevention group, 61% (38/62) dropped out (7 were hospitalised, 23 died, 8 others causes). In the primary prevention group, only one patient had worsening skin condition. In the secondary prevention group, 17.7% (11/62: 95% CI: 8.3-27.2) of patients had worsening skin condition. The number of PUs decreased regardless of location. At the end of follow-up, 49% (45/92) of patients had a PU versus 67% (62/92) at baseline CONCLUSION: This work provides data on the incidence of PUs in patients at high risk, who are using APAMs, and, following inpatient hospitalisation, are taken into home health-care centres. The results of the study highlight the importance of continuity of care across transitions between care settings. PMID- 26562379 TI - Disrupting the biofilm matrix improves wound healing outcomes. AB - OBJECTIVE: The most unyielding molecular component of biofilm communities is the matrix structure that it can create around the individual microbes that constitute the biofilm. The type of polymeric substances (polymeric sugars, bacterial proteins, bacterial DNA and even co-opted host substances) are dependent on the microbial species present within the biofilm. The extracellular polymeric substances that make up the matrix give the wound biofilm incredible colony defences against host immunity, host healing and wound care treatments. This polymeric slime layer, which is secreted by bacteria, encases the population of microbes, creating a physical barrier that limits the ingress of treatment agents to the bacteria. The aim of this study was to determine if degrading the wound biofilm matrix would improve wound healing outcomes and if so, if there was a synergy between treating agents that disrupted biofilm defenses with Next Science Wound Gel (wound gel) and cidal agents (topical antibiotics). METHOD: A three-armed randomised controlled trial was designed to determine if standard of care (SOC) was superior to SOC plus wound gel (SOC + gel) and wound gel alone. The wound gel used in this study contains components that directly attack the biofilm extracellular polymeric substance. The gel was applied directly to the wound bed on a Monday-Wednesday-Friday interval, either alone or with SOC topical antibiotics. RESULTS: Using a surrogate endpoint of 50% reduction in wound volume, the results showed that SOC healed at 53%, wound gel healed at 80%, while SOC plus wound gel showed 93% of wounds being successfully treated. CONCLUSION: By directly targeting the wound biofilm matrix, wound healing outcomes are improved. PMID- 26562380 TI - Lateral malleolar region defects with exposed implants: proximally based peroneus brevis muscle flap. AB - OBJECTIVE: Reconstruction of lateral malleolar region defects with exposed implants is a problematic situation for the reconstructive surgeon because there are limited options. The objective of our study was to revise the management of these defects and point out the role of proximally based peroneus brevis muscle flap. METHOD: Patients with an implant exposed tissue defects of the lateral malleolar region were evaluated retrospectively. All defects reconstructed with proximally based peroneus brevis muscle flap were included in this study. RESULTS: Of the 17 patients identified the mean age was 37.1 years (range 16-58 years). The size of the defects were 2-9cm in length (mean: 4.9cm) and 2-4cm in width (mean: 2.6cm). All defects were successfully covered with proximally based peroneus brevis muscle flaps combined with split-thickness skin grafts. All flaps healed with no complication or need for secondary surgery. The mean follow-up was18.8 months (range 12-32 months). CONCLUSION: Proximally based peroneus brevis muscle flap is a good alternative for reconstruction of lateral malleolar region defects with reliable blood supply, short surgical time, and minimal donor site morbidity. PMID- 26562381 TI - The challenge of objective scar colour assessment in a clinical setting: using digital photography. AB - OBJECTIVE: Scar assessment in the clinical setting is typically impeded by a lack of quantitative data and most systems rely on subjective rating scales which are user dependant and show considerable variability between raters. The growing use of digital photography in medicine suggests a more objective approach to scar evaluation. Our objective was to determine if cameras could be of practical use for measuring colour in a clinical setting. METHOD: The measurement of colour and reflectance spectra in photographs faces two difficulties: firstly the effects of variable illumination spectra, and secondly to recover accurate colour and spectral information from the sparse red, green and blue (RGB) camera signals. As a result the colour rendition is often inaccurate, and spectral information is lost. To deal with variable illumination and other factors that systematically affect all reflectance spectra ColourWorker (a method for image-based colour measurement implemented in software) calibrates the spectral responses of the camera's RGB sensors using a colour standard in the image. To make best use of the calibrated signals, it takes advantage of the fact that although a given RGB signal can be caused by an infinite number of spectra, most natural reflectance spectra vary smoothly and have predictable forms. This means given a set of examples of spectra produced by the materials of interest, it is possible to estimate the specific spectrum that produced a given RGB signal once corrected for the illumination. We describe a method for recovering spectral and chromatic information relating to surface reflectance from ordinary digital images and apply this to analyse photographs of surgical scars, taken as part of a clinical trial, in an attempt to better quantify clinical scar assessment. It should be noted the pre-existing trial protocol did not allow for a comprehensive evaluation of the accuracy of the method which would require the spectrophotometric measurement of skin regions corresponding to those in the photographs. RESULTS: Scar colour was estimated reliably, and with simple image analysis we were able to record the change in colour across the skin. Furthermore, we describe a simple automated assessment procedure that enables scar severity to be quantified and defined using a single scalar value easily. CONCLUSION: Such image-based colour measurement and assessment offers considerable advantages over other current methods, including spectrometers, which measure only a single point, or printed charts. PMID- 26562382 TI - Danish translation and validation of the International Skin Tear Advisory Panel Skin Tear Classification System. AB - OBJECTIVE: The aim of this study was to translate, validate and establish reliability of the International Skin Tear Classification System in Danish. METHOD: Phase 1 of the project involved the translation of the International Skin Tear Advisory Panel (ISTAP) Skin Tear Classification System into Danish, using the forward-back translation method described by the principles of good practice for the translation process for patient-reported outcomes. In Phase 2, the Danish group sought to replicate the ISTAP validation study and validate the classification system with registered nurses (RN) and social and health-care assistants (non-RN) from both primary health care and a Danish university hospital in Copenhagen. Thirty photographs, with equal representation of the three types of skin tears, were selected to test validity. The photographs chosen were those originally used for internal and external validation by the ISTAP group. The subjects were approached in their place of work and invited to participate in the study and to attend an educational session related to skin tears. RESULTS: The Danish translation of the ISTAP classification system was tested on 270 non-wound specialists. The ISTAP classification system was validated by 241 RNs, and 29 non-RN. The results indicated a moderate level of agreement on classification of skin tears by type (Fleiss' Kappa=0.460). A moderate level of agreement was demonstrated for both the RN group and the non-RN group (Fleiss' Kappa=0.464 and 0.443, respectively). CONCLUSION: The ISTAP Skin Tear Classification System was developed with the goal of establishing a global language for describing and documenting skin tears and to raise the health-care community's awareness of skin tears. The Danish translation of the ISTAP classification system supports the earlier ISTAP study and further validates the classification system. The Danish translation of the classification system is vital to the promotion of skin tears in both research and the clinical settings in Denmark. PMID- 26562383 TI - MicroRNAs Come of Age in Diagnostics. PMID- 26562384 TI - Origin of the Enigmatic Stepwise Tight-Binding Inhibition of Cyclooxygenase-1. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, fever, inflammation, and some types of cancers. Their mechanism of action is the inhibition of isoforms 1 and 2 of the enzyme cyclooxygenase (COX-1 and COX-2, respectively). However, both nonselective and selective NSAIDs may have side effects that include gastric intestinal bleeding, peptic ulcer formation, kidney problems, and occurrences of myocardial infarction. The search for selective high-affinity COX inhibitors resulted in a number of compounds characterized by a slow, tight-binding inhibition that occurs in a two-step manner. It has been suggested that the final, only very slowly reversible, tight binding event is the result of conformational changes in the enzyme. However, the nature of these conformational changes has remained elusive. Here we explore the structural determinants of the tight-binding phenomenon in COX-1 with molecular dynamics and free energy simulations. The calculations reveal how different classes of inhibitors affect the equilibrium between two conformational substates of the enzyme in distinctly different ways. The class of tight-binding inhibitors is found to exclusively stabilize an otherwise unfavorable enzyme conformation and bind significantly stronger to this state than to that normally observed in crystal structures. By also computing free energies of binding to the two enzyme conformations for 16 different NSAIDs, we identify an induced-fit mechanism and the key structural features associated with high-affinity tight binding. These results may facilitate the rational development of new COX inhibitors with improved selectivity profiles. PMID- 26562390 TI - A Fitting Memorial. PMID- 26562389 TI - Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis. AB - RATIONALE: Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. OBJECTIVES: To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. METHODS: In this cross sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. MEASUREMENTS AND MAIN RESULTS: We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. CONCLUSIONS: BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB. PMID- 26562391 TI - 2015 JCO Orthodontic Practice Study, Part 1 Trends. PMID- 26562392 TI - Accuracy of 3D Facial Models Obtained from CBCT Volume Wrapping. PMID- 26562393 TI - Intrusion of Supraerupted Second Molars with the Palatal Intrusion Fork. PMID- 26562394 TI - An Efficient Way to Document Aligner Appointments. PMID- 26562395 TI - Distal Movement of Lower Molars with Miniplate Anchorage. PMID- 26562396 TI - Retreatment of a Class II Patient with Short-Root Anomaly. PMID- 26562397 TI - Testing the transferability of a coarse-grained model to intrinsically disordered proteins. AB - The intermediate-resolution coarse-grained protein model PLUM [T. Bereau and M. Deserno, J. Chem. Phys., 2009, 130, 235106] is used to simulate small systems of intrinsically disordered proteins involved in biomineralisation. With minor adjustments to reduce bias toward stable secondary structure, the model generates conformational ensembles conforming to structural predictions from atomistic simulation. Without additional structural information as input, the model distinguishes regions of the chain by predicted degree of disorder, manifestation of structure, and involvement in chain dimerisation. The model is also able to distinguish dimerisation behaviour between one intrinsically disordered peptide and a closely related mutant. We contrast this against the poor ability of PLUM to model the S1 quartz-binding peptide. PMID- 26562398 TI - Equal detection rate of cervical heterotopic gastric mucosa in standard white light, high definition and narrow band imaging endoscopy. AB - BACKGROUND AND AIM: The prevalence of cervical heterotopic gastric mucosa (HGM) of the proximal oesophagus differs widely between studies, perhaps due to examination conditions during endoscopy. In this study we aimed to determine whether narrow band imaging (NBI) or high definition (HD) imaging improves detection of HGM. Possible factors of influence for HGM detection, in particular setting (position, timing, in-/out-patient), examination time and sedation parameters, were analysed. METHODS: Retrospective analysis of 641 consecutive patients who underwent an oesophagogastroduodenoscopy (EGD) by the same, substantially experienced endoscopist between June 2011 and August 2013. The type of endoscope was randomly assigned to patients. RESULTS: A total of 85 patients showed HGM with an overall prevalence of 13.3 %. The detection rate in the HD-NBI group was 18/127 (14.2 %) and in the HD white light (HDWL) group, 15/104 (14.4 %, p = 0.957). The detection rate between standard definition white light (SDWL) endoscopy (52/410, 12.7 %) and HD endoscopy did not differ significantly (33/231, 14.3 %, p = 0.566). Setting, sedation dosage and examination times were equally distributed between study groups. The indication of dysphagia (11.8 % vs. 2.4 % with p = 0.000, respectively) and dyspepsia (19.1 % vs. 10.8 %, p = 0.047, respectively) occurred significantly more often in HGM patients than in the control group. There was no difference in the detection rate depending on HGM size. CONCLUSIONS: The prevalence of HGM in the upper EGD is high and does not differ significantly between the study groups of SDWL, HDWL and HD-NBI under equivalent conditions. PMID- 26562399 TI - Color Doppler ultrasound-guided PTBD with and without metal stent implantation by endoscopic control: prospective success and early adverse event rates. AB - OBJECTIVE: There are just a few reports on Color Doppler Ultrasound-guided PTBD with and without metal stent implantation by endoscopic control. Ultrasound guidance facilitates percutaneous bile duct access and avoids severe adverse events. Internal biliary drainage rate in PTBD should be as high as possible as endoscopic ultrasound-guided cholangiodrainage (EUCD) offers internal drainage regularly. We report our prospective study analyzing success, internal drainage and adverse event rates. MATERIALS AND METHODS: Between June 2009 and November 2014 overall 63 PTBDs were performed prospectively in 37 patients (18 m, 19f; age on average: 72 years) with benign (9 %) and malignant (91 %) bile duct obstruction. Ultrasound was used in combination with fluoroscopic guidance. Whenever possible, primary or early secondary metal stent implantation via PTBD by endoscopic control was performed as a one step-procedure. RESULTS: 38 of 41 (93 %) initial PTBDs (in four patients PTBD was performed twice) were successful. 22 of 63 PTBDs were follow-up examinations with different interventions. In 34 of 38 successful (89 %) PTBDs, an internal drainage (or metal stent) was implanted. 12 metal stent implantations via PTBD were performed under endoscopic control. Just 2 (5 %) permanent external drainages were inserted. In 63 performed PTBDs 5 (7.9 %) early major adverse events (no severe intrahepatic bleeding) were documented and treated without any procedure related death. When metal stent implantation was performed via PTBD no adverse event was documented. CONCLUSION: Color Doppler guided PTBD is an effective and safe method for biliary drainage avoiding severe adverse events. Primary or early secondary metal stent implantation via PTBD reduces complication risks additionally. Endoscopic control of stent implantation via PTBD is helpful for optimal stent placement. PMID- 26562400 TI - [Jejunal ulcerations - a diagnostic challenge in a patient with coeliac disease]. AB - A subset of patients with coeliac disease (CD) suffers persistent or recurrent complaints despite a strict adherence to a gluten-free diet (GFD) that can be caused by refractory coeliac disease (RCD). We present a patient with weight loss and signs of malassimilation secondary to villous atrophy and jejunal ulcerations complicating known CD. We demonstrate a stepwise approach to the diagnosis and subtyping of RCD and to rule out important alternative causes of jejunal ulcerations. RCD can be classified as type I based on the absence or as type II based on the presence of an aberrant intestinal mucosal lymphocyte population. RCD type I shows a more benign course as these patients usually improve on a treatment consisting of nutritional support and immunosuppressive therapies such as budesonide or azathioprine. In contrast, clinical response to standard therapies in RCD type II is less certain and the prognosis is poor. Several groups suggest that RCD type II should be regarded as low-grade intraepithelial lymphoma which frequently transforms into an aggressive enteropathy associated T cell lymphoma with a high mortality rate. Therefore, a rapid differentiation of RCD type I and RCD type II is a major clinical challenge to early initiate appropriate treatment modalities. PMID- 26562401 TI - [Primary liver tumours in childhood]. AB - The reported prevalence of focal liver lesions in adult patients and children is different. The article discusses pediatric liver tumors under the criteria of histopathology and contrast enhanced ultrasound (CEUS) features. Aim of this article is also to support the already established Pediatric Registry of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) to collect data on safety and applications of ultrasound contrast agents in children (www.efsumb.org). PMID- 26562402 TI - [Clinical impact of infections with carbapenem-resistant enterobacteriaceae in liver transplant recipients]. AB - Infections with carbapenem-resistant Enterobacteriaceae (CRE) are an emerging cause of morbidity and mortality among liver transplant recipients (LTR) worldwide, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Approximately 3 - 13 % of solid organ transplant recipients in CRE endemic areas develop CRE infections, and the infection site correlates with the transplanted organ. The cumulative 30-day mortality rate of LTR infected with carbapenem-resistant K. pneumoniae is 36 %, and the 180-day mortality rate is 58 %. Awareness of the high vulnerability of LTR to fatal bacterial infection leads to the more frequent use of ultrabroad-spectrum empirical antibiotic therapy, which further contributes to the selection of extreme drug resistance. Moreover, it comprises a relevant risk of failure to initiate adequate empirical treatment due to the fact that culture-based techniques used to identify CRE imply a 48- to 72-hour delay from blood culture collection until administration of the targeted therapy. This vicious circle is difficult to avoid and leads to increased clinical intricacy and narrowed antimicrobial therapeutic options. Because available options are extremely limited, infection prevention measures have gained outstanding importance, particularly in the phase after liver transplant requiring intense immunosuppression early on. Improving clinical outcomes is a major challenge and involves a multi-targeted approach combining strictly applied hygiene measures, active surveillance tests, the use of modern, time-saving methods of molecular biology, and enforced antibiotic stewardship. This article reviews the current literature regarding the incidence and outcome of CRE infections in LTR, and it summarises current preventive and therapeutic recommendations to minimise the threat by CRE in real-life clinical transplant settings. PMID- 26562404 TI - [Risk of pancreatic cancer in chronic pancreatitis - lower than previously supposed?]. PMID- 26562403 TI - [Not Available]. PMID- 26562405 TI - [The INCA trial (impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver cirrhosis and ascites): precision medicine for patients with liver cirrhosis and ascites]. PMID- 26562407 TI - The existence of 5-hydroxymethylcytosine and 5-formylcytosine in both DNA and RNA in mammals. AB - We developed a novel strategy by oxidation-derivatization combined mass spectrometry analysis for the determination of 5-hydroxymethylcytosine and 5 formylcytosine in both DNA and RNA. We reported the presence of 5-formylcytosine in RNA of mammals and found that ascorbic acid and hydroquinone can increase the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in DNA and RNA. PMID- 26562406 TI - Regulation of Spatiotemporal Patterns by Biological Variability: General Principles and Applications to Dictyostelium discoideum. AB - Spatiotemporal patterns often emerge from local interactions in a self-organizing fashion. In biology, the resulting patterns are also subject to the influence of the systematic differences between the system's constituents (biological variability). This regulation of spatiotemporal patterns by biological variability is the topic of our review. We discuss several examples of correlations between cell properties and the self-organized spatiotemporal patterns, together with their relevance for biology. Our guiding, illustrative example will be spiral waves of cAMP in a colony of Dictyostelium discoideum cells. Analogous processes take place in diverse situations (such as cardiac tissue, where spiral waves occur in potentially fatal ventricular fibrillation) so a deeper understanding of this additional layer of self-organized pattern formation would be beneficial to a wide range of applications. One of the most striking differences between pattern-forming systems in physics or chemistry and those in biology is the potential importance of variability. In the former, system components are essentially identical with random fluctuations determining the details of the self-organization process and the resulting patterns. In biology, due to variability, the properties of potentially very few cells can have a driving influence on the resulting asymptotic collective state of the colony. Variability is one means of implementing a few-element control on the collective mode. Regulatory architectures, parameters of signaling cascades, and properties of structure formation processes can be "reverse-engineered" from observed spatiotemporal patterns, as different types of regulation and forms of interactions between the constituents can lead to markedly different correlations. The power of this biology-inspired view of pattern formation lies in building a bridge between two scales: the patterns as a collective state of a very large number of cells on the one hand, and the internal parameters of the single cells on the other. PMID- 26562408 TI - Association Between Graft Storage Time and Donor Age With Endothelial Cell Density and Graft Adherence After Descemet Membrane Endothelial Keratoplasty. AB - IMPORTANCE: After retrospectively evaluating the clinical outcome of 500 consecutive cases after Descemet membrane endothelial keratoplasty (DMEK), we extended the analysis in this study by assessing the effect of donor-related parameters on endothelial cell density (ECD) decline and detachment rate in this group. OBSERVATIONS: This retrospective case series included 500 cases who had undergone DMEK from October 2007 to September 2012 at the Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, the Netherlands. Logistic regression analysis (n = 332 eyes) showed that donor age might be associated with a 3% increase in the risk for a detachment (odds ratio, 0.97; 95% CI, 0.94-1.00; P = .049) (ie, higher donor age seems to be associated with lower chances of a detachment). In addition, linear regression analysis indicated that graft storage time in medium was associated with ECD decrease (ie, the longer the storage time, the larger the decrease at 6 months after DMEK) (P = .01). CONCLUSIONS AND RELEVANCE: We showed an association between graft storage time and ECD decline after DMEK and possibly between donor age and graft detachment. Therefore, donor storage times should be kept as short as possible to improve short-term ECDs. More research is needed to draw definite conclusions on the possible effect of donor age on the chance of a detachment after DMEK. PMID- 26562409 TI - Cognitive Changes During Chemotherapy. PMID- 26562411 TI - Correction: Exploration of Novel Inhibitors for Class I Histone Deacetylase Isoforms by QSAR Modeling and Molecular Dynamics Simulation Assays. PMID- 26562412 TI - Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery. AB - BACKGROUND: Recently, it has been reported that specific microRNA (miRNA) levels are elevated in serum and can be used as biomarkers in patients with cardiovascular diseases. However, miRNAs expression profiles and their sources in pericardial fluid (PF) are unclear. METHODS AND RESULTS: The purpose of this study was to identify the levels of miRNAs in PF in relation to those in the serum in patients undergoing cardiac surgery. Serum (S) and PF from patients undergoing coronary artery bypass graft (CABG) due to stable angina pectoris (sAP) and unstable AP (uAP) and aortic valve replacement due to aortic stenosis (AS) were analyzed for the detection of miRNAs. We named these samples S-sAP, S uAP, S-AS, PF-sAP, PF-uAP, and PF-AS, respectively. We first measured the levels of miR-423-5p, which was recognized previously as a biomarker for heart failure. miR-423-5p levels were significantly higher in PF than serum. Although there was no difference in miR-423-5p levels among the PF-AS, PF-sAP, and PF-uAP, its levels were significantly elevated in S-uAP compared with those in S-AS and S sAP. In order to clarify the source of miR-423-5p in PF, we measured the levels of muscle-enriched miR-133a and vascular-enriched miR-126 and miR-92a in the same samples. miR-133a levels were significantly higher in serum than in PF, and it was elevated in S-uAP compared with S-AS. miR-126 level was significantly increased in serum compared with PF, and the level of miR-92a the similar tendency. miR-423-5p is located in the first intron of NSRP1. There is another miRNA, miR-3184, encoded in the opposite direction in the same region. In vitro experiments indicated that the duplex of miR-423-5p and miR-3184-3p was more resistant to RNase than the duplex of miR-423-5p and miR-133-3p, which may help to stabilize miR-423-5p in the PF. CONCLUSIONS: Our results suggested that miR 423-5p is enriched in PF, and serum miR-423-5p may be associate with uAP. Its expression pattern was different to that of muscle- and vascular-enriched miRNAs, miR-133a, miR-126, and miR-92a. PMID- 26562413 TI - An ab initio molecular dynamics analysis of lignin as a potential antioxidant for hydrocarbons. AB - Lignins are complex phenolic polymers with limited industrial uses. To identify new applications of lignins, this study aims to evaluate the conifer alcohol lignin as a potential antioxidant for hydrocarbons, using the petroleum asphalt as an example. Using the ab initio molecular dynamics (AIMD) method, the evaluation is accomplished by tracking the generation of critical species in a lignin-asphalt mixture under a simulated oxidative condition. The generation of new species was detected using nuclear magnetic resonance and four analytical methods including density of states analysis, highest occupied molecular orbital and lowest unoccupied molecular orbital analyses, bonding and energy level analysis, and electrostatic potential energy analysis. Results of the analyses show that the chemical radicals of carbon, nitrogen and sulfur generated in the oxidation process could enhance the agglomeration and/or decomposition tendency of asphalt. The effectiveness of lignins as an antioxidant depends on their chemical compositions. Lignins with a HOMO-LUMO gap larger than the HOMO-LUMO gap of the hydrocarbon system to be protected, such as the conifer alcohol lignin to protect petroleum asphalt as was studied in this work, do not demonstrate beneficial anti-oxidation capacity. Lignins, however, may be effective oxidants for hydrocarbon systems with a larger HOMO-LUMO gap. In addition, lignins may contain more polar sites than the hydrocarbons to be protected; thus the lignins' hydrophobicity and compatibility with the host hydrocarbons need to be well evaluated. The developed AIMD model provides a useful tool for developing antioxidants for generic hydrocarbons. PMID- 26562410 TI - Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages. AB - Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts. PMID- 26562415 TI - Development of Lentivirus-Based Reference Materials for Ebola Virus Nucleic Acid Amplification Technology-Based Assays. AB - The 2013-present Ebola virus outbreak in Western Africa has prompted the production of many diagnostic assays, mostly based on nucleic acid amplification technologies (NAT). The calibration and performance assessment of established assays and those under evaluation requires reference materials that can be used in parallel with the clinical sample to standardise or control for every step of the procedure, from extraction to the final qualitative/quantitative result. We have developed safe and stable Ebola virus RNA reference materials by encapsidating anti sense viral RNA into HIV-1-like particles. The lentiviral particles are replication-deficient and non-infectious due to the lack of HIV-1 genes and Envelope protein. Ebola virus genes were subcloned for encapsidation into two lentiviral preparations, one containing NP-VP35-GP and the other VP40 and L RNA. Each reference material was formulated as a high-titre standard for use as a calibrator for secondary or internal standards, and a 10,000-fold lower titre preparation to serve as an in-run control. The preparations have been freeze-dried to maximise stability. These HIV-Ebola virus RNA reference materials were suitable for use with in-house and commercial quantitative RT-PCR assays and with digital RT-PCR. The HIV-Ebola virus RNA reference materials are stable at up to 37 degrees C for two weeks, allowing the shipment of the material worldwide at ambient temperature. These results support further evaluation of the HIV-Ebola virus RNA reference materials as part of an International collaborative study for the establishment of the 1st International Standard for Ebola virus RNA. PMID- 26562416 TI - Effective Suppression of Methane Emission by 2-Bromoethanesulfonate during Rice Cultivation. AB - 2-bromoethanesulfonate (BES) is a structural analogue of coenzyme M (Co-M) and potent inhibitor of methanogenesis. Several studies confirmed, BES can inhibit CH4 prodcution in rice soil, but the suppressing effectiveness of BES application on CH4 emission under rice cultivation has not been studied. In this pot experiment, different levels of BES (0, 20, 40 and 80 mg kg-1) were applied to study its effect on CH4 emission and plant growth during rice cultivation. Application of BES effectively suppressed CH4 emission when compared with control soil during rice cultivation. The CH4 emission rates were significantly (P<0.001) decreased by BES application possibly due to significant (P<0.001) reduction of methnaogenic biomarkers like Co-M concentration and mcrA gene copy number (i.e. methanogenic abunadance). BES significantly (P<0.001) reduced methanogen activity, while it did not affect soil dehydrogenase activity during rice cultivation. A rice plant growth and yield parameters were not affected by BES application. The maximum CH4 reduction (49% reduction over control) was found at 80 mg kg-1 BES application during rice cultivation. It is, therefore, concluded that BES could be a suitable soil amendment for reducing CH4 emission without affecting rice plant growth and productivity during rice cultivation. PMID- 26562414 TI - Integrins and integrin-related proteins in cardiac fibrosis. AB - Cardiac fibrosis is one of the major components of the healing mechanism following any injury of the heart and as such may contribute to both systolic and diastolic dysfunction in a range of pathophysiologic conditions. Canonically, it can occur as part of the remodeling process that occurs following myocardial infarction or that follows as a response to pressure overload. Integrins are cell surface receptors which act in both cellular adhesion and signaling. Most importantly, in the context of the continuously contracting myocardium, they are recognized as mechanotransducers. They have been implicated in the development of fibrosis in several organs, including the heart. This review will focus on the involvement of integrins and integrin-related proteins, in cardiac fibrosis, outlining the roles of these proteins in the fibrotic responses in specific cardiac pathologies, discuss some of the common end effectors (angiotensin II, transforming growth factor beta 1 and mechanical stress) through which integrins function and finally discuss how manipulation of this set of proteins may lead to new treatments which could prove useful to alter the deleterious effects of cardiac fibrosis. PMID- 26562417 TI - Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring. AB - AIM: Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation. METHODS: Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR. RESULTS: Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1beta mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes. CONCLUSIONS: Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired immune sensing. PMID- 26562421 TI - Decision Making About Treatment for Advanced Cancer: Influencing Wisely? PMID- 26562418 TI - Vibrio cholerae Serogroup O139: Isolation from Cholera Patients and Asymptomatic Household Family Members in Bangladesh between 2013 and 2014. AB - BACKGROUND: Cholera is endemic in Bangladesh, with outbreaks reported annually. Currently, the majority of epidemic cholera reported globally is El Tor biotype Vibrio cholerae isolates of the serogroup O1. However, in Bangladesh, outbreaks attributed to V. cholerae serogroup O139 isolates, which fall within the same phylogenetic lineage as the O1 serogroup isolates, were seen between 1992 and 1993 and in 2002 to 2005. Since then, V. cholerae serogroup O139 has only been sporadically isolated in Bangladesh and is now rarely isolated elsewhere. METHODS: Here, we present case histories of four cholera patients infected with V. cholerae serogroup O139 in 2013 and 2014 in Bangladesh. We comprehensively typed these isolates using conventional approaches, as well as by whole genome sequencing. Phenotypic typing and PCR confirmed all four isolates belonging to the O139 serogroup. FINDINGS: Whole genome sequencing revealed that three of the isolates were phylogenetically closely related to previously sequenced El Tor biotype, pandemic 7, toxigenic V. cholerae O139 isolates originating from Bangladesh and elsewhere. The fourth isolate was a non-toxigenic V. cholerae that, by conventional approaches, typed as O139 serogroup but was genetically divergent from previously sequenced pandemic 7 V. cholerae lineages belonging to the O139 or O1 serogroups. CONCLUSION: These results suggest that previously observed lineages of V. cholerae O139 persist in Bangladesh and can cause clinical disease and that a novel disease-causing non-toxigenic O139 isolate also occurs. PMID- 26562422 TI - Decision Making About Treatment for Advanced Cancer-Reply. PMID- 26562424 TI - Incorrect Author Academic Degree and Incomplete Name. PMID- 26562423 TI - Association Between Obesity and Postmenopausal Breast Cancer Risk: Modification by Hormone Therapy Use. PMID- 26562425 TI - Association Between Obesity and Postmenopausal Breast Cancer Risk-Reply. PMID- 26562426 TI - Misspelled Author Name. PMID- 26562427 TI - Addition to Reference List. PMID- 26562428 TI - Error in Byline. PMID- 26562429 TI - An Agent-Based Model of Private Woodland Owner Management Behavior Using Social Interactions, Information Flow, and Peer-To-Peer Networks. AB - Privately owned woodlands are an important source of timber and ecosystem services in North America and worldwide. Impacts of management on these ecosystems and timber supply from these woodlands are difficult to estimate because complex behavioral theory informs the owner's management decisions. The decision-making environment consists of exogenous market factors, internal cognitive processes, and social interactions with fellow landowners, foresters, and other rural community members. This study seeks to understand how social interactions, information flow, and peer-to-peer networks influence timber harvesting behavior using an agent-based model. This theoretical model includes forested polygons in various states of 'harvest readiness' and three types of agents: forest landowners, foresters, and peer leaders (individuals trained in conservation who use peer-to-peer networking). Agent rules, interactions, and characteristics were parameterized with values from existing literature and an empirical survey of forest landowner attitudes, intentions, and demographics. The model demonstrates that as trust in foresters and peer leaders increases, the percentage of the forest that is harvested sustainably increases. Furthermore, peer leaders can serve to increase landowner trust in foresters. Model output and equations will inform forest policy and extension/outreach efforts. The model also serves as an important testing ground for new theories of landowner decision making and behavior. PMID- 26562430 TI - From System-Wide Differential Gene Expression to Perturbed Regulatory Factors: A Combinatorial Approach. AB - High-throughput experiments such as microarrays and deep sequencing provide large scale information on the pattern of gene expression, which undergoes extensive remodeling as the cell dynamically responds to varying environmental cues or has its function disrupted under pathological conditions. An important initial step in the systematic analysis and interpretation of genome-scale expression alteration involves identification of a set of perturbed transcriptional regulators whose differential activity can provide a proximate hypothesis to account for these transcriptomic changes. In the present work, we propose an unbiased and logically natural approach to transcription factor enrichment. It involves overlaying a list of experimentally determined differentially expressed genes on a background regulatory network coming from e.g. literature curation or computational motif scanning, and identifying that subset of regulators whose aggregated target set best discriminates between the altered and the unaffected genes. In other words, our methodology entails testing of all possible regulatory subnetworks, rather than just the target sets of individual regulators as is followed in most standard approaches. We have proposed an iterative search method to efficiently find such a combination, and benchmarked it on E. coli microarray and regulatory network data available in the public domain. Comparative analysis carried out on artificially generated differential expression profiles, as well as empirical factor overexpression data for M. tuberculosis, shows that our methodology provides marked improvement in accuracy of regulatory inference relative to the standard method that involves evaluating factor enrichment in an individual manner. PMID- 26562432 TI - Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11beta knock-down. AB - Peroxisomes constitute special cellular organelles which display a variety of metabolic functions including fatty acid oxidation and free radical elimination. Abundance of these flexible organelles varies in response to different environmental stimuli. It has been demonstrated that PEX11beta, a peroxisomal membrane elongation factor, is involved in the regulation of size, shape and number of peroxisomes. To investigate the role of PEX11beta in neural differentiation of mouse embryonic stem cells (mESCs), we generated a stably transduced mESCs line that derives the expression of a short hairpin RNA against Pex11beta gene following doxycycline (Dox) induction. Knock-down of Pex11beta, during neural differentiation, significantly reduced the expression of neural progenitor cells and mature neuronal markers (p<0.05) indicating that decreased expression of PEX11beta suppresses neuronal maturation. Additionally, mRNA levels of other peroxisome-related genes such as PMP70, Pex11alpha, Catalase, Pex19 and Pex5 were also significantly reduced by Pex11beta knock-down (p<0.05). Interestingly, pretreatment of transduced mESCs with peroxisome proliferator activated receptor gamma agonist (pioglitazone (Pio)) ameliorated the inhibitory effects of Pex11beta knock down on neural differentiation. Pio also significantly (p<0.05) increased the expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mESC. Results elucidated the importance of Pex11beta expression in neural differentiation of mESCs, thereby highlighting the essential role of peroxisomes in mammalian neural differentiation. The observation that Pio recovered peroxisomal function and improved neural differentiation of Pex11beta knocked-down mESCs, proposes a potential new pharmacological implication of Pio for neurogenesis in patients with peroxisomal defects. PMID- 26562433 TI - Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins. AB - Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. However, the widely accepted biomarkers for autism are still lacking. In this study, we carried out a quantitative proteomic profiling study of cortical brain tissue from BTBR T(+)Itpr3(tf) (BTBR) mice, a mouse model that displays an autism-like phenotype. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS, a total of 3611 proteins were quantitated in mouse cortices. As compared to C57BL/6J (B6) mice, 126 differentially expressed proteins were found in the brain from BTBR mice. The functional annotation and categories of differentially expressed proteins were analyzed. Especially, the stable tubule only polypeptide (STOP) protein and myelin-related proteins down-regulated significantly in BTBR mice were confirmed by Western blotting. Furthermore, the BTBR mice displayed reduced levels of staining with ferric alum in comparison to B6 controls, indicative of myelin disruption. Finally, we propose that reduced STOP expression in the brain could be involved in the mediation of autism-like behaviors through impairments of myelination in oligodendrocytes and synaptic function in neurons. Manipulation of STOP protein could be a promising avenue for therapeutic interventions to autism. PMID- 26562431 TI - Using mice to model Obsessive Compulsive Disorder: From genes to circuits. AB - Obsessive Compulsive Disorder (OCD) is a severe, chronic, and highly prevalent psychiatric disorder that affects between 1.5% and 3% of people worldwide. Despite its severity, high prevalence, and clear societal cost, current OCD therapies are only partially effective. In order to ultimately develop improved treatments for this severe mental illness, we need further research to gain an improved understanding of the pathophysiology that underlies obsessions and compulsions. Though studies in OCD patients can provide some insight into the disease process, studies in humans are inherently limited in their ability to dissect pathologic processes because of their non-invasive nature. The recent development of strategies for genetic and circuit-specific manipulation in rodent models finally allows us to identify the molecular, cellular, and circuit events that lead to abnormal repetitive behaviors and affect dysregulation relevant to OCD. This review will highlight recent studies in mouse model systems that have used transgenic and optogenetic tools in combination with classic pharmacology and behavioral techniques to advance our understanding of these pathologic processes. PMID- 26562434 TI - HIV Incidence Prior to, during, and after Violent Conflict in 36 Sub-Saharan African Nations, 1990-2012: An Ecological Study. AB - OBJECTIVES: The aim of this study was to determine the association between violent conflict and HIV incidence within and across 36 sub-Saharan Africa countries between 1990 and 2012. METHODS: We used generalized linear mixed effect modeling to estimate the effect of conflict periods on country-level HIV incidence. We specified random intercepts and slopes to account for across and within country variation over time. We also conducted a sub-analysis of countries who experienced conflict to assess the effect of conflict intensity on country level HIV incidence. All models controlled for level of economic development, number of refugees present in the country, and year. RESULTS: We found that, compared to times of peace, the HIV incidence rate increased by 2.1 per 1000 infections per year (95%CI: 0.39, 3.87) in the 5 years prior to conflict. Additionally, we found a decrease of 0.7 new infections per 1000 people per year (95%CI: -1.44, -0.01) in conflicts with 25 to 1000 battle-related deaths and a decrease of 1.5 new infections per 1000 people per year (95%CI:-2.50, -0.52) for conflict with more than 1000 battle-related deaths, compared to conflicts with less than 25 battle-related deaths. CONCLUSIONS: Our results demonstrate that HIV infection rates increase in the years immediately prior to times of conflict; however, we did not identify a significant increase during and immediately following periods of violent conflict. Further investigation, including more rigorous data collection, is needed, as is increased aid to nations at risk of violent conflict to help in the fight against HIV/AIDS in sub-Saharan Africa. PMID- 26562435 TI - Leptospira and Bats: Story of an Emerging Friendship. PMID- 26562437 TI - Autophagy activation attenuates angiotensin II-induced cardiac fibrosis. AB - Autophagy has been involved in numerous diseases processes. However, little is known about the role of autophagy in cardiac fibrosis. Thus, whether or not angiotensin II (Ang II)-induced autophagy has a regulatory function on cardiac fibrosis was detected in vitro and in vivo. In rat cardiac fibroblasts (CFs) stimulated with Ang II, activated autophagy was observed using transmission electron microscopic analysis (TEM), immunofluorescence and Western blot. In Ang II-infused mice, increased co-localization of LC3 puncta with vimentin was observed. In rat CFs, co-treated with rapamycin (Rapa), an autophagy inducer, Ang II-induced the upregulation of type I collagen (Col-I), fibronectin (FN) was decreased. Conversely, inhibition of autophagy by chloroquine (CQ), an autophagy inhibitor, or knockdown of ATG5, a key component of the autophagy pathway by specific siRNA, aggravated Ang II-mediated the accumulation of Col-I and FN. Furthermore, in C57 BL/6 mice with Ang II infusion, intraperitoneal administration of Rapa ameliorated Ang II-induced cardiac fibrosis and cardiac dysfunction, while CQ treatment not only exacerbated Ang II-mediated cardiac fibrosis and cardiac dysfunction, but also impaired cardiac function. These findings suggest that autophagy may exert a protective role to attenuate excess extracellular matrix (ECM) accumulation in the heart. PMID- 26562436 TI - Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil. AB - OBJECTIVE: To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil. METHODS: We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population. RESULTS: Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5). CONCLUSION: It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission. PMID- 26562438 TI - Deletion of Dual Specificity Phosphatase 1 Does Not Predispose Mice to Increased Spontaneous Osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease with poorly understood etiology and pathobiology. Mitogen activated protein kinases (MAPKs) including ERK and p38 play important roles in the mediation of downstream pathways involved in cartilage degenerative processes. Dual specificity phosphatase 1 (DUSP1) dephosphorylates the threonine/serine and tyrosine sites on ERK and p38, causing deactivation of downstream signalling. In this study we examined the role of DUSP1 in spontaneous OA development at 21 months of age using a genetically modified mouse model deficient in Dusp1 (DUSP1 knockout mouse). RESULTS: Utilizing histochemical stains of paraffin embedded knee joint sections in DUSP1 knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age. A semi-quantitative cartilage degeneration scoring system also demonstrated similar scores in the various aspects of the knee joint articular cartilage in DUSP1 knockout and control mice. Examination of overall articular cartilage thickness in the knee joint demonstrated similar results between DUSP1 knockout and wild type mice. Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups. Likewise, immunostaining for phosphoERK and MMP13 showed similar intensity and localization between groups. SOX9 immunostaining demonstrated a decreased number of positive cells in DUSP1 knockout mice, with correspondingly decreased staining intensity. Analysis of animal walking patterns (gait) did not show a discernable difference between groups. CONCLUSION: Loss of DUSP1 does not cause changes in cartilage degeneration and gait in a mouse model of spontaneous OA at 21 months of age. Altered staining was observed in SOX9 immunostaining which may prove promising for future studies examining the role of DUSPs in cartilage and OA, as well as models of post-traumatic OA. PMID- 26562439 TI - Exploring the evolutionary rate differences between human disease and non-disease genes. AB - Comparisons of evolutionary features between human disease and non-disease genes have a wide implication to understand the genetic basis of human disease genes. However, it has not yet been resolved whether disease genes evolve at slower or faster rate than the non-disease genes. To resolve this controversy, here we integrated human disease genes from several databases and compared their protein evolutionary rates with non-disease genes in both housekeeping and tissue specific group. We noticed that in tissue specific group, disease genes evolve significantly at a slower rate than non-disease genes. However, we found no significant difference in evolutionary rates between disease and non-disease genes in housekeeping group. Tissue specific disease genes have a higher protein complex number, elevated gene expression level and are also associated with conserve biological processes. Finally, our regression analysis suggested that protein complex number followed by protein multifunctionality independently modulates the evolutionary rate of human disease genes. PMID- 26562442 TI - Global Mittag-Leffler synchronization of fractional-order neural networks with discontinuous activations. AB - This paper is concerned with the global Mittag-Leffler synchronization for a class of fractional-order neural networks with discontinuous activations (FNNDAs). We give the concept of Filippov solution for FNNDAs in the sense of Caputo's fractional derivation. By using a singular Gronwall inequality and the properties of fractional calculus, the existence of global solution under the framework of Filippov for FNNDAs is proved. Based on the nonsmooth analysis and control theory, some sufficient criteria for the global Mittag-Leffler synchronization of FNNDAs are derived by designing a suitable controller. The proposed results enrich and enhance the previous reports. Finally, one numerical example is given to demonstrate the effectiveness of the theoretical results. PMID- 26562440 TI - Gene expression profiling in stroke: relevance of blood-brain interaction. AB - Biomarker profiling is utilized to identify diagnostic and prognostic candidates for stroke. Clinical and preclinical biomarker data suggest altered circulating immune responses may illuminate the mechanisms of stroke recovery. However, the relationship between peripheral blood biomarker profile(s) and brain profiles following stroke remains elusive. Data show that neutrophil lymphocyte ratio (NLR) predicts stroke outcome. Neutrophils release Arginase 1 (ARG1) resulting in T lymphocyte suppression in peripheral blood. Interestingly, the cellular response to stroke may have implications for known biomarker profiles. Conversely, preclinical evidence suggests that upregulation of ARG1 in microglia is a marker of M2 macrophages and may influence neuroprotection. Comparing clinical and preclinical studies creates opportunities to explore the molecular mechanisms of blood and brain biomarker interactions in stroke. PMID- 26562443 TI - GABAergic Neurotransmission in the Premammillary Nucleus of the Turkey Hypothalamus Regulates Reproductive Seasonality and the Onset of Photorefractoriness. AB - BACKGROUND/AIMS: Photoperiod is a major environmental cue in temperate-zone birds which synchronizes breeding with the time of year that offers the optimal environment for offspring survival. Despite continued long photoperiods, these birds eventually become refractory to the stimulating photoperiod and their reproductive systems regress. In this study, we characterized the role of gamma aminobutyric acid (GABA)ergic neurotransmission in modulating the response of the premammillary nucleus (PMM) to a gonad stimulatory photoperiod and the onset of photorefractoriness. METHODS AND RESULTS: Bilateral ablation of the PMM blocked the light-induced neuroendocrine response from occurring in photosensitive turkeys. Microarray analyses revealed an increase in GABAergic activity in the PMM of photorefractory birds as opposed to photosensitive ones, and this enhanced GABAergic activity appeared to inhibit the photoperiodic signal. Additionally, GABAA and GABAB receptors were expressed by dopamine-melatonin neurons in the PMM, and the administration of the GABA receptor agonist baclofen blocked the photoperiodic reproductive neuroendocrine responses. CONCLUSIONS: Consistent with the present findings, we propose that the long-sought-after mechanism underlying photorefractoriness is linked to the inhibitory actions of GABA. We suggest that (1) GABAergic interference with photoperiodic entrainment in the PMM initiates the photorefractory state and terminates the annual breeding season in temperate zone birds, and (2) the PMM is a site of photoreception and photorefractoriness that controls the initiation and termination of avian reproductive seasonality. PMID- 26562444 TI - Droplet evaporation on a horizontal substrate under gravity field by mesoscopic modeling. AB - The evaporation of water drop deposited on a horizontal substrate is investigated using a lattice Boltzmann method (LBM) for multiphase flows with a large-density ratio. To account for the variation of evaporation flux distribution along the drop interface, a novel evaporation scheme is introduced into the LBM framework, and validated by comparison with experimental data. We aim at discovering the effect of gravity on the evaporating drop in detail, and various evaporation conditions are considered as well as different wetting properties of the substrates. An effective diameter is introduced as an indicator of the critical drop size under which gravity is negligible. Our results show that such critical diameter is much smaller than the capillary length, which has been widely accepted as the critical size in previous and current works. The critical diameter is found to be almost independent of the evaporation conditions and the surface wettability. A correlation between this critical diameter and the capillary length is also proposed for easy use in applications. PMID- 26562445 TI - Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins. AB - Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX 2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning. PMID- 26562446 TI - Enhancement of yellow pigment production by intraspecific protoplast fusion of Monascus spp. yellow mutant (ade(-)) and white mutant (prototroph). AB - To breed industrially useful strains of a slow-growing, yellow pigment producing strain of Monascus sp., protoplasts of Monascus purpureus yellow mutant (ade(-)) and rapid-growing M. purpureus white mutant (prototroph) were fused and fusants were selected on minimal medium (MM). Preliminary conventional protoplast fusion of the two strains was performed and the result showed that only white colonies were detected on MM. It was not able to differentiate the fusants from the white parental prototroph. To solve this problem, the white parental prototroph was thus pretreated with 20mM iodoacetamide (IOA) for cytoplasm inactivation and subsequently taken into protoplast fusion with slow-growing Monascus yellow mutant. Under this development technique, only the fusants, with viable cytoplasm from Monascus yellow mutant (ade(-)), could thus grow on MM, whereas neither IOA pretreated white parental prototroph nor yellow auxotroph (ade(-)) could survive. Fifty-three fusants isolated from yellow colonies obtained through this developed technique were subsequently inoculated on complete medium (MY agar). Fifteen distinguished yellow colonies from their parental yellow mutant were then selected for biochemical, morphological and fermentative properties in cassava starch and soybean flour (SS) broth. Finally, three most stable fusants (F7, F10 and F43) were then selected and compared in rice solid culture. Enhancement of yellow pigment production over the parental yellow auxotroph was found in F7 and F10, while enhanced glucoamylase activity was found in F43. The formation of fusants was further confirmed by monacolin K content, which was intermediate between the two parents (monacolin K-producing yellow auxotroph and non-monacolin K producing white prototroph). PMID- 26562447 TI - Measurements of radiation exposure of dentistry students during their radiological training using thermoluminescent dosimetry. AB - Exposure among dentistry students has not been assessed or regulated in Mexico. This work assessed the average exposure of 35 dentistry students during their training with the aid of LiF:Mg,Cu,P+PTFE thermoluminescent dosimeters. For the students in the roles of dentist and observers, maximum accumulated equivalent dose obtained was 2.59+/-0.11 and 4.64+/-0.39 mSv, respectively. Students in the role as patients received a maximum accumulated effective dose of 28.41+/-0.31 mSv. If compared to occupational dose limits, this latter value is 56% of the recommended value of 50 mSv in any year. It was found that in all cases, values of equivalent dose to the women breasts were equal to the background dose. Results are discussed and compared to previous published work. Suggested recommendations were given to authorities in order to minimize exposure of the students in the role as patients. PMID- 26562448 TI - Neutron energy spectrum adjustment using deposited metal films on Teflon in the miniature neutron source reactor. AB - The focus of this article was on the experimental estimation of the neutron energy spectrum in the inner irradiation site of the miniature neutron source reactor (MNSR), using, for the first time, a selected set of deposited metal films on Teflon (DMFTs) neutron detectors. Gold, copper, zinc, titanium, aluminum, nickel, silver, and chromium were selected because of the dependence of their neutron cross-sections on neutron energy. Emphasis was placed on the usability of this new type of neutron detectors in the total neutron energy spectrum adjustment. The measured saturation activities per target nucleus values of the DMFTs, and the calculated neutron spectrum in the inner irradiation site using the MCNP-4C code were used as an input for the STAY'SL computer code during the adjustment procedure. The agreement between the numerically calculated and experimentally adjusted spectra results was discussed. PMID- 26562449 TI - Preliminary study of the applicability of the thin gap method on alpha emitters. AB - The thin gap method as an in-situ radiotracer technique is widely used. This study investigated the applicability of alpha emitters. PIPS and CsI alpha spectrometers were applied in a thin gap cell. A suitable (210)Po source was prepared by spontaneous deposition, Mylar foil was used to simulate water. A maximum intensity decrement of 7% within 25 MUm was observed. Even though this method is suitable for the study of surface phenomena, further investigation is necessary e.g. into water and heat sensitivity. PMID- 26562450 TI - An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron. AB - An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. PMID- 26562451 TI - Trophic status and meiofauna biodiversity in the Northern Adriatic Sea: Insights for the assessment of good environmental status. AB - The Descriptor 5 (Eutrophication) of the EU Marine Strategy Framework Directive aims at preventing the negative effects of eutrophication. However, in coastal systems all indicators based on water column parameters fail in identifying the trophic status and its effects on biodiversity and ecosystem functioning. We investigated benthic trophic status, in terms of sedimentary organic matter quantity, composition and quality, along with meiofaunal abundance, richness of taxa and community composition in three coastal sites (N Adriatic Sea) affected by different levels of anthropogenic stressors. We show that, on the basis of organic matter quantity and composition, the investigated areas can be classified from oligo-to mesotrophic, whereas using meiofauna as a descriptor, their environmental quality ranged from sufficient to moderately impacted. Our results show that the benthic trophic status based on organic matter variables, is not sufficient to provide a sound assessment of the environmental quality in marine coastal ecosystems. However, data reported here indicate that the integration of the meiofaunal variable allows providing robust assessments of the marine environmental status. PMID- 26562453 TI - AMSSM Scientific Statement Concerning Viscosupplementation Injections for Knee Osteoarthritis: Importance for Individual Patient Outcomes. AB - OBJECTIVE: Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection [hyaluronic acid (HA)] versus steroid [intra-articular corticosteroid (IAS)] and placebo [intra-articular placebo (IAP)] is based on the evaluation of treatment effect by examining the number of subjects within a treatment arm that met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups was clinically different. DATA SOURCES: We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE, and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. MAIN RESULTS: Eleven articles met the inclusion criteria from the search strategy. On NMA, those subjects receiving HA were 15% and 11% more likely to respond to treatment by the OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (P < 0.05 for both). CONCLUSIONS: In light of the aforementioned results of our NMA, the American Medical Society for Sport Medicine recommends the use of HA for the appropriate patients with knee OA. PMID- 26562454 TI - Global routine vaccination coverage, 2014. AB - The year 2014 marked the 40th anniversary of the World Health Organization's (WHO) Expanded Program on Immunization, which was established to ensure equitable access to routine immunization services (1). Since 1974, global coverage with the four core vaccines (Bacille Calmette- Guerin vaccine [BCG; for protection against tuberculosis], diphtheria-tetanus-pertussis [DTP] vaccine, poliovirus vaccine, and measles vaccine) has increased from <5% to >=85%, and additional vaccines have been added to the recommended schedule. Coverage with the 3rd dose of DTP vaccine (DTP3) by age 12 months is an indicator of immunization program performance because it reflects completion of the basic infant immunization schedule; coverage with other vaccines, including the 3rd dose of poliovirus vaccine (polio3); the 1st dose of measles-containing vaccine (MCV1) is also assessed. Estimated global DTP3 coverage has remained at 84%-86% since 2009, with estimated 2014 coverage at 86%. Estimated global coverage for the 2nd routine dose of measles-containing vaccine (MCV2) was 38% by age 24 months and 56% when older age groups were included, similar to levels reported in 2013 (36% and 55%, respectively). To reach and sustain high immunization coverage in all countries, adequate vaccine stock management and additional opportunities for immunization, such as through routine visits in the second year of life, are integral components to strengthening immunization programs and reducing morbidity and mortality from vaccine preventable diseases. PMID- 26562455 TI - Development and Psychometric Testing of the Turkish-Version Oral Chemotherapy Adherence Scale. AB - BACKGROUND: To ensure the quality of patient care, the bioavailability of drugs, and the success of the treatment, it is imperative that nurses evaluate the adherence of patients to pharmaceutical treatments using standard measurement tools that are integrated into the treatment process. No scale that uses psychometric analyses to evaluate this adherence in patients who are on oral chemotherapy is currently available. PURPOSE: This study developed and tested the validity and reliability of a Turkish version of the standardized Oral Chemotherapy AdherenceScale (OCAS), a tool that may be used by healthcare personnel to better evaluate patient adherence to their therapies. METHODS: We developed and examined the validity and reliability of the OCAS using a sample of 306 patients with cancer who were receiving oral chemotherapy. A literature review was conducted to generate the items. An expert panel evaluated content validity; preimplementation was used to evaluate face validity, factor analysis was used to evaluate construct validity, and criterion validity was evaluated using the Medication Adherence Self-Efficacy Scale. RESULTS: The Cronbach's alpha calculated for OCAS (19 items) was .738. A highly significant and positive correlation was observed between the test-retest scores of the participants. A positive significant correlation was observed between the total scores of the participants obtained from OCAS and Medication Adherence Self-Efficacy Scale. As a result of the factor analysis performed for the construct validity of the scale, three factors were defined that accounted for approximately 43% of the total variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The OCAS has acceptable psychometric properties and is appropriate for use in research and clinical practice settings to evaluate patient adherence to their therapies. PMID- 26562456 TI - Cultural Competence and Related Factors Among Taiwanese Nurses. AB - BACKGROUND: Taiwan is a multicultural and multiethnic society with a growing number of immigrants who have diverse ethnic, racial, and cultural needs. Although this diversity highlights the pressing need for culturally competent healthcare providers, cultural competence is a concept that is little understood and implemented only sporadically in Taiwan. PURPOSE: This study investigates the cultural competence of Taiwanese nurses and the related factors of influence. METHODS: An online self-report survey was used to collect data from 221 Taiwanese nurses from December 2012 through January 2013. Data from the demographic questionnaire, the Nurses' Cultural Competence Scale, and the Perceived Nurses' Cultural Competence Rating were analyzed using descriptive statistics, Pearson correlation, independent sample t tests, and multiple regressions. RESULTS: The cultural competence of the participants was in the "low to moderate" range, with relatively higher mean scores for the subscales of cultural awareness and cultural sensitivity and relatively lower scores for the subscales of cultural knowledge and cultural skills. Participants generally perceived themselves as being "not culturally competent." Variables found to predict cultural competence included years of work experience, hours of continuing education related to cultural nursing care, and frequency of caring for clients from culturally and ethnically diverse backgrounds. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Participating Taiwanese nurses rated their level of cultural competence as in the low-to-moderate range and self-perceived as being not culturally competent. These findings support the need to further expand and enhance cultural-competence related continuing education and to address the topic of cultural care in the nursing curricula. PMID- 26562457 TI - Predictors of Sedentary Behavior in Elderly Koreans With Hypertension. AB - BACKGROUND: The older adults are the most sedentary of all age groups. Sedentary behavior is associated with the onset and exacerbation of hypertension and the deterioration of health in hypertensive patients. PURPOSE: The aims of this study were to examine the level of sedentary behavior and to identify the factors predicting sedentary behavior in elderly Koreans with hypertension. METHODS: A cross-sectional descriptive design was used. Three hundred six hypertensive elderly subjects who visited three public health centers in Korea for regular medical checkups completed self-report questionnaires on sedentary behavior, physical activity, empowerment, perceived health, depression, self-efficacy for physical activity, and social support for physical activity. RESULTS: The participants spent an average of 8.59 hours a day in sedentary behavior. The stepwise multiple regression analysis showed that sedentary behavior was significantly predicted by empowerment level, perceived health, time since diagnosis of hypertension, vigorous-intensity physical activity, and depression. These variables explained 42.6% of the variance in sedentary behavior. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: To reduce sedentary behavior in this population, future interventions should improve empowerment and perceived health, increase the intensity of physical activity, and alleviate depression while considering the duration of disease. PMID- 26562458 TI - Predictors of Glycemic Control in Adolescents of Various Age Groups With Type 1 Diabetes. AB - BACKGROUND: Understanding the predictors of glycemic control in adolescents of various age groups with type 1 diabetes (T1D) is crucial for nurses to cultivate developmental-specific interventions to improve glycemic control in this age group. However, research has rarely addressed this issue, particularly in the context of Asian populations. PURPOSE: We explored the predictive influence of demographic characteristics, self-care behaviors, family conflict, and parental involvement on glycosylated hemoglobin (HbA1C) levels 6 months after the baseline measurement in adolescents of various age groups with T1D in Taiwan. METHODS: A prospective survey design was applied. At baseline, adolescents with T1D completed a self-care behavior scale. Parents or guardians finished scales of parental involvement and family conflict. The HbA1C levels 6 months after baseline measurement were collected from medical records. Two hundred ten adolescent-parent/guardian pairs were enrolled as participants. Multiple stepwise regressions examined the significant predictors of HbA1C levels 6 months after the baseline measurement in the three adolescent age groups: 10-12, 13-15, and 16 18 years. RESULTS: Family conflict was a significant predictor of HbA1C level within the 10-12 years of age group 6 months after the baseline measurement. Self care behaviors were a significant predictor of HbA1C level within the 13-15 years of age group 6 months after the baseline measurement. Being female and self-care behaviors were each significant predictors of HbA1C level in the 16-18 years of age group 6 months after the baseline measurement. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Nurses should design specific interventions to improve glycemic control in adolescents of various age groups with T1D that are tailored to their developmental needs. For adolescents with T1D aged 10-12 years, nurses should actively assess family conflict and provide necessary interventions. For adolescents with T1D aged 13-18 years, nurses should exert special efforts to improve their self-care behaviors. In addition, female adolescents aged 16-18 years should be considered an at-risk group. PMID- 26562459 TI - Comparison of Pregnancy Stress Between In Vitro Fertilization/Embryo Transfer and Spontaneous Pregnancy in Women During Early Pregnancy. AB - BACKGROUND: Women who undergo in vitro fertilization/embryo transfer (IVF/ET) face complicated psychological stress and negative emotions, which may affect health during pregnancy and the development of the fetus. The current literature does not address the question of whether women who become pregnant spontaneously and women who undergo IVF face similar levels of pregnancy stress. PURPOSE: This study investigates the differences in pregnancy stress between women with spontaneous pregnancy and women with IVF/ET pregnancy living in central Taiwan during their first 20 weeks of pregnancy. METHODS: A prospective, longitudinal design with repeated measures, generalized estimated equations model, Wilks' lambda, and Bonferroni test was used. Purposive samples of 163 women who had undergone IVF/ET and of 94 women who had undergone spontaneous pregnancy were enrolled as participants. Pregnancy stress was measured using the Chinese version of the self-administered Pregnancy Stress Scale at the 9th, 12th, and 20th weeks of pregnancy. RESULTS: The psychological stress experienced by IVF participants significantly increased with gestational week during the first 20 weeks of pregnancy (p < .01) but did not significantly increase in spontaneous-pregnancy participants. Gestational week was the main factor found to influence stress ratings for "identifying maternal role." "Altering body structure and body function" was the main factor found to influence pregnancy stress (p < .00). The method of becoming pregnant had no significant influence on pregnancy stress during the first 20 weeks of pregnancy (p > .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this study provide clinical evidence that IVF/ET does not cause more stress for women than spontaneous pregnancy. However, the intensity and trend of stresses differed between these two groups. These findings suggest that nurses should consider method of pregnancy when assessing the risk of stress in expectant mothers for each gestational week and when providing appropriate care and support. PMID- 26562460 TI - The Meaning of Disease and Spiritual Responses to Stressors in Adults With Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Some studies have shown that patients with cancer may experience significant spiritual distress as well as spiritual growth, that there is a positive association between spirituality and coping, and that positive religious coping predicts enhanced health outcomes. PURPOSE: This study was designed to help explain how the meaning of disease and spiritual responses to threatening stressors influence the final experiential outcomes of adults with leukemia undergoing hematopoietic stem cell transplantation in Iran. METHODS: This grounded theory study conducted in-depth interviews between 2009 and 2011 on 10 adults in Iran with leukemia undergoing hematopoietic stem cell transplantation. Recorded audio interviews were transcribed verbatim in Persian and coded and analyzed using Corbin and Strauss (2008)'s approach. RESULTS: Main categories that emerged from data included "experiencing the meaning of cancer"; "changing perceptions of death, life and health"; and "moving toward perfection and sublimity." "Finding meaning" was the main concept that defined the final outcome of the experience of participants. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Understanding the meaning to patients of disease and treatments may help healthcare providers better appreciate the patients' perspective and improve the physician-patient relationship. Nurses are well positioned to play a decisive role in helping patients cope effectively with their treatment process and in helping ensure positive outcomes for treatments through their helping patients find the unique meaning of their experience. PMID- 26562461 TI - The Stress of Caring for Children With Asthma: A Qualitative Study of Primary Caregivers. AB - BACKGROUND: Asthma is one of the most common chronic diseases in children. The unpredictability, frequency, and health risks associated with acute asthma attacks have a profound impact on the daily lives of affected children and their families. Understanding the experiences of primary caregivers may help nurses provide better care to children with asthma. PURPOSE: This study explores the experience of primary caregivers in providing care to children with asthma. METHODS: The study used exploratory and descriptive research methods and collected data using a qualitative research interview approach. Seventeen primary caregivers of children with asthma who visited the allergy clinics of two medical centers and one regional hospital in northern Taiwan participated in the study. An interview guide with a semistructured questionnaire was used, and verbatim transcripts of the audiotape-recorded interviews were analyzed using content analysis. RESULTS: The findings are described in three themes covering 10 categories. These themes and categories include feelings of uncertainty during illness (disease as perception related, lack of information), feelings of chaos and instability (worry, fear, frustration, helplessness, physical distress), and social tension and family conflict (disorientation of daily activity and burden of care, economic burden, family tensions and disagreements). CONCLUSIONS: Negative experiences with asthma care and the unpredictability of the disease outcomes impair the ability of caregivers to adapt successfully to their caregiving role and encourage perceptions that they cannot cope with this illness. Better understanding the caregiver experience may assist healthcare providers to better target support to these caregivers so that they are better able to care for children with asthma. PMID- 26562462 TI - Perceptions of Pediatric Critical Care Nurses on the Initiation of a Nursing-Led Feeding Protocol. AB - BACKGROUND: Critically ill children frequently receive inadequate nutritional support. Feeding protocols have been shown to facilitate optimal nutritional care. PURPOSE: We aim to determine the perceptions of critical care nurses with regard to the implementation of a feeding protocol as well as to their preferred teaching methods before introducing this protocol in our pediatric intensive care unit (PICU). We hypothesize that nursing experience and educational level are factors that predict readiness to adopt this protocol. METHODS: All PICU nurses were invited to participate in an online survey to investigate their perceptions on protocol implementation and on preferred teaching methods. Statistical analysis was performed using simple logistic regression and the Fisher exact test. Statistical significance was taken as p < .05. RESULTS: Seventy-four nurses completed the survey. Fifty-four (73%) had nursing degrees. Mean duration of PICU experience was 6.2 years (5th, 95th percentile: 1, 15). Three quarters of participants (74%, n = 55) felt that they did not have sufficient knowledge regarding feeding protocols, and 86% (n = 64) expressed that they were keen to implement a feeding protocol. There was no association between readiness to adopt the feeding protocol with years of ICU experience (OR = 0.99, 95% CI [0.84, 1.18]) and educational level (OR = 1.43, 95% CI [0.31, 6.68]). The preferred teaching methods were bedside teaching (61%), didactic lectures (51%), and the distribution of protocol manuals (50%). PICU nurses felt that the advantages of a feeding protocol included standardization of practice, optimization of patient's nutritional intake, earlier initiation of feeding, increased patient safety, and the extension of nursing roles. Perceived disadvantages included inapplicability of the feeding protocol to all patients, lack of flexibility in feeding management, increased confusion, and doctors placing little value on the feeding protocol. CONCLUSIONS: This study found that nursing experience and level of education do not significantly affect the readiness of nurses to adopt a feeding protocol. Medical and nursing teams should not shy away from introducing a new protocol although their nurses have little experience or prior knowledge of that protocol. Future studies to investigate the impact of tailoring of educational needs before introduction of a new protocol are necessary to study the overall effectiveness of this teaching before introducing a new protocol in the ICU. PMID- 26562463 TI - The Perspectives of Iranian Women on Delayed Childbearing: A Qualitative Study. AB - BACKGROUND: Delayed childbearing is a growing trend in Iran. PURPOSE: This study explores the perspectives of women on delayed childbearing. METHODS: A qualitative study using a content analysis approach was conducted on data acquired using private semistructured interviews with 23 women aged >=30 years who were childless or pregnant for the first time in an urban area of Iran. RESULTS: Three main themes were developed using conventional content analysis: "personal inclination," "perceived beliefs about delayed childbearing," and "social support." CONCLUSIONS: Although women in Iran hold favorable attitudes toward childbearing, a wide range of sociocultural and economic factors encourage these women to postpone their first pregnancy. The findings of this study are relevant and important for nursing and midwifery policy making in countries with cultural and contextual backgrounds similar to Iran. PMID- 26562464 TI - Factors Associated With the Development of Delirium in Elderly Patients in Intensive Care Units. AB - BACKGROUND: High prevalence rates of delirium have been found in intensive care units (ICUs), ranging from 20% to 80%. The development of delirium may prolong length of stay, impair cognition, and result in placement in a nursing home for the patient. PURPOSE: There is a lack of research focused on the aging population, so the purpose of this study was to establish the incidence rate of delirium among ICU elderly patients and to identify its risk factors. METHODS: An observational design with repeated measures was used. Subjects older than 65 years who had been admitted to the ICU within 24 hours were recruited. The Confusion Assessment Method for the Intensive Care Unit and Richmond Agitation Sedation Scale were used twice a day to identify subjects experiencing delirium by RA. The demographic data, history of illness, Acute Physiology and Chronic Health Evaluation II scores, and laboratory data of the participants were recorded. RESULTS: Ninety participants were included from a medical ICU. The incidence rate of delirium was 75.6% (n = 68). Average age was 78.28 +/- 7.6 years; Acute Physiology and Chronic Health Evaluation II scores ranged from 7 to 35. Most participants were diagnosed with respiratory failure (73.3%), and 86.76% of participants developed delirium within 24 hours. The most frequently experienced type of delirium was the mixed subtype (47.05%); the second most frequently experienced was hypoactive next. The risk factors were analyzed using logistic regression. The number of anesthetic analgesics used, total number of medications prescribed, duration of dehydration, use of corticosteroids before admissions, and shock were identified and explained 31.3% of variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Delirium is a severe problem among elderly patients in the ICU. Healthcare professionals should pay more attention to elderly patients at greater risk for experiencing delirium. PMID- 26562466 TI - Covalent Immobilization of Caged Liquid Crystal Microdroplets on Surfaces. AB - Microscale droplets of thermotropic liquid crystals (LCs) suspended in aqueous media (e.g., LC-in-water emulsions) respond sensitively to the presence of contaminating amphiphiles and, thus, provide promising platforms for the development of new classes of droplet-based environmental sensors. Here, we report polymer-based approaches to the immobilization of LC droplets on surfaces; these approaches introduce several new properties and droplet behaviors and thus also expand the potential utility of LC droplet-based sensors. Our approach exploits the properties of microscale droplets of LCs contained within polymer based microcapsule cages (so-called "caged" LCs). We demonstrate that caged LCs functionalized with primary amine groups can be immobilized on model surfaces through both weak/reversible ionic interactions and stronger reactive/covalent interactions. We demonstrate using polarized light microscopy that caged LCs that are covalently immobilized on surfaces can undergo rapid and diagnostic changes in shape, rotational mobility, and optical appearance upon the addition of amphiphiles to surrounding aqueous media, including many useful changes in these features that cannot be attained using freely suspended or surface-adsorbed LC droplets. Our results reveal these amphiphile-triggered orientational transitions to be reversible and that arrays of immobilized caged LCs can be used (and reused) to detect both increases and decreases in the concentrations of model contaminants. Finally, we report changes in the shapes and optical appearances of LC droplets that occur when immobilized caged LCs are removed from aqueous environments and dried, and we demonstrate that dried arrays can be stored for months without losing the ability to respond to the presence of analytes upon rehydration. Our results address practical issues associated with the preparation, characterization, storage, and point-of-use application of conventional LC-in-water emulsions and provide a basis for approaches that could enable the development of new "off-the-shelf" LC droplet-based sensing platforms. PMID- 26562467 TI - Regioselective ortho Amination of Coordinated 2-(Arylazo)pyridine. Isolation of Monoradical Palladium Complexes of a New Series of Azo-Aromatic Pincer Ligands. AB - In an unusual reaction of [Pd(L(1))Cl2] (L(1) = 2-(arylazo)pyridine) with amines, a new series of palladium complexes [Pd(L(2*-))Cl] (L(2) = 2-((2 amino)arylazo)pyridine) (1a-1h) were isolated. The complexes were formed via N-H and N-C bond cleavage reactions of 1 degrees /2 degrees and 3 degrees amines, respectively, followed by regioselective aromatic ortho-C-N bond formation reaction and are associated with ortho-C-H/ortho-C-Cl bond activation. A large variety of amines including both aromatic and aliphatic were found to be effective in producing air-stable complexes. Identity of the resultant complexes was confirmed by their X-ray structure determination. Efforts were also made to understand the mechanism of the reaction. A series of experiments were performed, which point toward initial ligand reduction followed by intraligand electron transfer. Examination of the structural parameters of these complexes (1) indicates that the in situ generated ligand coordinated to the Pd(II) center serves as the backbone of these air-stable monoradical complexes. Molecular and electronic structures of the isolated complexes were further scrutinized by various spectroscopic techniques including cyclic voltammetry, variable temperature magnetic susceptibility measurements, electron paramagnetic resonance, and UV-vis spectroscopy. Finally the electronic structure was confirmed by density functional theory calculations. The isolated monoradical complexes adopt an unusual pi-stacked array, which leads to a relatively strong antiferromagnetic interaction (J = -40 cm(-1) for the representative complex 1c). PMID- 26562468 TI - Enhancing Cellular Uptake and Doxorubicin Delivery of Mesoporous Silica Nanoparticles via Surface Functionalization: Effects of Serum. AB - In this study, we demonstrate how functional groups on the surface of mesoporous silica nanoparticles (MSNPs) can influence the encapsulation and release of the anticancer drug doxorubicin, as well as cancer cell response in the absence or presence of serum proteins. To this end, we synthesized four differently functionalized MSNPs with amine, sulfonate, polyethylene glycol, or polyethylene imine functional surface groups, as well as one type of antibody-conjugated MSNP for specific cellular targeting, and we characterized these MSNPs regarding their physicochemical properties, colloidal stability in physiological media, and uptake and release of doxorubicin in vitro. Then, the MSNPs were investigated for their cytotoxic potential on cancer cells. Cationic MSNPs could not be loaded with doxorubicin and did therefore not show any cytotoxic and antiproliferative potential on osteosarcoma cells, although they were efficiently taken up into the cells in the presence or absence of serum. In contrast, substantial amounts of doxorubicin were loaded into negatively charged and unfunctionalized MSNPs. Especially, sulfonate-functionalized doxorubicin-loaded MSNPs were efficiently taken up into the cells in the presence of serum and showed an accelerated toxic and antiproliferative potential compared to unfunctionalized MSNPs, antibody conjugated MSNPs, and even free doxorubicin. These findings stress the high importance of the surface charge as well as of the protein corona for designing and applying nanoparticles for targeted drug delivery. PMID- 26562469 TI - Immunologic advances reveal new targets in psoriasis and psoriatic arthritis. AB - Psoriatic arthritis (PsA) is a chronic inflammatory joint disorder with heterogeneous clinical features that may include plaque psoriasis, joint inflammation, enthesitis, dactylitis, and abnormal bone turn over. This disease is common, affecting up to 0.5% of the population with equal male and female prevalence. Until recently, few treatment options were available for PsA and patients suffered immense physical and social burden. Traditional disease modifying agents show limited efficacy in the treatment of PsA. Anti-tumor necrosis factor (TNF) drugs are effective for all the manifestations, yet recent studies show that up to 50% of patients either do not tolerate these medications or do not maintain a clinical response. The evolution in the treatment of PsA emerged from improved understanding of the pathophysiology of the disease with Th1 and Th17 cells taking center stage. Targeting TNF along with cytokines in the IL-23/TH17 pathway (IL-23, IL-17, and IL-22) holds great promise for improved treatment outcomes in PsA. PMID- 26562471 TI - CD19 chimeric antigen receptor T cell therapy for the treatment of B cell lineage acute lymphoblastic leukemia. AB - Relapsed and refractory acute lymphoblastic leukemia (ALL) remains difficult to treat, with minimal improvement in outcomes despite advances in upfront therapy and improved survival for de novo ALL. Targeted immunotherapy for cancer represents a promising new treatment and utilizing the immune system to target and eradicate malignant cells in the body has emerged as a potent therapy. Administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 have been shown to induce complete responses in patients with B-cell lineage ALL. So far, six clinical trials including 79 ALL patients treated with CD19-CAR T cells have been published, and the results from these trials are exciting with impressive clinical responses. Thus, CAR T cell therapy represents a potential useful tool to ALL. However, the majority of CAR cell studies have observed severe therapy associated toxicities, which needs attention. In this review, we mainly focus on CD19-CAR T cells, clinical trials for ALL as well as toxicities and challenges for CD19-CAR T therapy. PMID- 26562470 TI - Discovery of the drivers of inflammation induced chronic low back pain: from bacteria to diabetes. AB - The intervertebral disc is a unique avascular organ that supports axial skeleton flexion and rotation. The high proteoglycan content of the nucleus pulposus tissue, present at the center of the disc, is pivotal for its mechanical function, distribution of compressive loads. Chronic low back pain, a prevalent and costly condition, is strongly associated with disc degeneration. Degenerated discs exhibit high levels of inflammatory cytokines, matrix catabolizing enzymes, and an overall reduction in proteoglycan content. Although the cytokine profile of diseased discs has been widely studied, little is known of what initiates and drives inflammation and subsequent low back pain. Recent studies have shown that anaerobic bacteria are present in a high percentage of painful, herniated discs and long-term treatment with antibiotics resolves symptoms associated with chronic low back pain. It is thought that these anaerobic bacteria in the disc may stimulate inflammation through toll-like receptors to further exacerbate disc degeneration. Despite the promise and novelty of this theory, there are other possible inflammatory mediators that need careful consideration. The metabolic environment associated with diabetes and atypical matrix degradation products also have the ability to activate many of the same inflammatory pathways as seen during microbial infection. It is therefore imperative that the research community must investigate the contribution of all possible drivers of inflammation to address the wide spread problem of discogenic chronic low back pain. PMID- 26562473 TI - Sonodynamic treatment as an innovative bimodal anticancer approach: shock wave mediated tumor growth inhibition in a syngeneic breast cancer model. AB - Despite the great advances in fighting cancer, many therapies still have serious side effects, thus urging the development of highly selective and safe treatments with a wide range of applicability. Sonodynamic therapy (SDT) is an innovative bimodal anticancer approach in which two normally non-toxic components -- one chemical, a sonosensitizer, and one physical, ultrasound -- selectively combine to cause oxidative damage and subsequent cancer cell death. In this study, we investigate the anticancer effect of SDT using shock waves (SWs) to activate protoporphyrin IX (PpIX) cytotoxicity on a Mat B-III syngeneic rat breast cancer model. The SDT-treated group saw a significant decrease (p<0.001) in magnetic resonance imaging (MRI) tumor size measurements 72 hours after treatment with PpIX precursor 5-aminolevulinic acid (ALA) and SWs. This occurred together with significant increase (p<0.01) in apparent diffusion coefficients between pre- and post-treatment MR tumor maps and strong increase in necrotic and apoptotic histological features 72 hours post-treatment. Moreover, significant HIF1A mRNA expression up-regulation was observed along with the prominent selective cleavage of poly (ADP-ribose) polymerase (PARP) and increased autophagy related protein LC3A/B expression in SDT-treated tumors, as compared to untreated tumors 72 hours post-treatment. Thus, the anticancer effect of SDT can be boosted by SWs, making them a valid technology for furthering investigations into this innovative anticancer approach. PMID- 26562472 TI - Continuation of gradual weight gain necessary for the onset of puberty may be responsible for obesity later in life. AB - A continuation of the gradual weight gain necessary for the onset of puberty may be responsible for obesity later in life. Hypothetically, a group of brain nuclei form components of a single pubertal clock mechanism that drives pre-pubertal weight gain and governs the onset of puberty and fertility. No mechanism evolved to shut off pre-pubertal and pubertal weight and body fat gain after puberty. The weight gain continues unabated throughout life. A better understanding of the mechanism of puberty and pre-pubertal weight gain could provide new insights into obesity and diseases associated with obesity such as type 2 diabetes, dyslipidemia, hypertension, heart disease, depression, etc. PMID- 26562474 TI - Mechanisms of epithelial-mesenchymal transition in proliferative vitreoretinopathy. AB - Proliferative vitreoretinopathy (PVR) is a blinding disease characterized by the formation of epiretinal membranes through the wound repair process. Though the mechanisms of PVR development are still not fully understood, retinal pigment epithelial (RPE) cells are indicated to play the primary role in the pathogenesis of PVR. In the setting of PVR, RPE cells undergo a process named epithelial mesenchymal transition (EMT), by which differentiated epithelial cells go through a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts. Recent studies indicated that EMT in RPE cells is a main contributor of PVR and involves various growth factors/cytokines, transcriptional factors, and microRNAs. Targeting these factors/microRNAs suppresses the progression of EMT and thus may provide novel ideas for the treatment of PVR. This review highlights the current understandings of EMT in the pathogenesis of PVR and the underlying mechanisms of EMT in RPE cells. PMID- 26562475 TI - Oct4 is a reliable marker of liver tumor propagating cells in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and the 2nd most common cause of cancer related mortality. The poor prognosis is largely due to the difficulty in early diagnoses and eradication of stem-like cells within HCC, which are termed liver tumor propagating cells (LTPCs). These LTPCs are involved in all stages of tumorigenesis including tumor initiation, progression, and treatment failure. The greatest challenge in understanding these LTPCs is finding effective ways in isolating and characterizing these cells with current methods showing large inter-tumor variability in isolating these cells. Oct4 is a stem cell gene associated with LTPCs and has been shown to be involved in regulating a range of functions in HCC cells associated with LTPC features. In this study we determined the efficacy and reliability in utilizing Oct4 to isolate and characterize LTPCs. We have shown that Oct4 is ubiquitously expressed in all HCC tumors tested whereas other traditional LTPC markers had high intratumor variability in their expression. We then utilized a human Oct4 promoter driving an enhanced green fluorescent protein (EGFP) reporter which showed that Oct4+ cells had all the classic features of LTPCs including increased sphere formation in vitro, tumor forming potential in immunocompromised mice, expression of stemness associated genes, and resistance to Sorafenib which is the major drug used to treat advanced HCC. Based on our findings we have identified Oct4 as a reliable marker of LTPCs and discovered a novel way to isolate and characterize LTPCs. PMID- 26562476 TI - Disease kinetics but not disease burden is relevant for survival in melanoma of unknown primary tumor. AB - Melanoma of unknown primary (MUP) is a type of metastatic melanoma with no evidence of a primary tumor. Recent evidence suggested better survival in MUP as compared to melanoma with a known primary site (MKP). However, prognostic markers that reliably predict overall survival in MUP are lacking. The primary objective of this study was to analyze the mutational status of the BRAF, NRAS, and KIT oncogenes and to investigate if the genotype or other clinical parameters were associated with overall survival. We retrospectively analyzed the genotype and the clinical course of 40 patients with MUP. Mutations of BRAF and NRAS were determined with pyrosequencing. Mutations of KIT were investigated with a nested PCR approach followed by Sanger sequencing. Survival fractions were calculated applying the Kaplan-Meier model. Mutations in the BRAF (50.0%), NRAS (17.5%), and KIT genes (5.0%) were found frequently, but had no major impact on overall survival (p=0.62). The AJCC stage was a strong prognostic factor with a hazard ratio for death of 0.17 (stage III vs. IV; p=0.04). All patients diagnosed with stage III disease survived the median follow-up period of 23 months (p=0.03). The survival rates of patients with stage IV were significantly associated with rapid disease progression but not with metastatic tumor load at primary diagnosis (p=0.01). Altogether, AJCC stage and time to disease progression were important prognostic parameters. We propose that the kinetics of the disease but not the initial metastatic burden nor the mutational status is relevant for survival in advanced MUP. PMID- 26562477 TI - Study of distinct serum proteomics for the biomarkers discovery in colorectal cancer. AB - To utilize surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to identify potential biomarkers for diagnosis, preoperative pathological classification, staging, and postoperative prognosis in patients with colorectal cancer (CRC), a total of 152 samples were analyzed in this study, including 53 untreated CRC, 12 colorectal adenoma, 15 healthy volunteers, 30 post-treatment CRC patients with stable disease, and 42 post treatment CRC with progressive disease. The samples were all analyzed by SELDI TOF-MS and CM10 ProteinChip technology. The proteomic profiles were validated using a bioinformatics tool based on support vector machine (SVM) and undecimated discrete wavelet transform (UDWT) methods. Seven protein peaks were selected as potential biomarkers for CRC, with a specificity of 85.19% and a sensitivity of 96.23%. Four protein peaks were selected as potential markers for colorectal mucinous adenocarcinoma and non-mucinous adenocarcinoma, with a specificity of 95.12% and sensitivity of 83.33%. In addition, SELDI-based serum profiling discriminated between patients with locally advanced (stage I-II) and regionally advanced (stage III) CRC, and between patients with locoregional (stage I-III) and systemic (stage IV) CRC, with high specificity and sensitivity. A protein peak at 5909 Da was identified as a potential marker for tumor progression and prognosis in CRC. In conclusion, we have demonstrated that ProteinChip technology with SELDI-TOF-MS could provide a novel, non-invasive tool for diagnosis, potential preoperative biomarkers for pathological classification, staging, and postoperative prognostic markers for patients with CRC. PMID- 26562478 TI - Reactions of Phenylhydrosilanes with Pincer-Nickel Complexes: Evidence for New Si O and Si-C Bond Formation Pathways. AB - This contribution presents evidence for new pathways manifested in the reactions of the phenylhydrosilanes PhnSiH4-n with the pincer complexes (POCsp(2)OP)Ni(OSiMe3), 1-OSiMe3, and (POCsp(3)OP)Ni(OSiMe3), 2-OSiMe3 (POCsp(2)OP = 2,6-(i-Pr2PO)2C6H3; POCsp(3)OP = (i-Pr2POCH2)2CH). Excess PhSiH3 or Ph2SiH2 reacted with 1-OSiMe3 to eliminate the disilyl ethers Ph(n)H(3-n)SiOSiMe3 (n = 1 or 2) and generate the nickel hydride species 1-H. Subsequent reaction of the latter with more substrate formed corresponding nickel silyl species 1-SiPhH2 or 1-SiPh2H and generated multiple Si-containing products, including disilanes and redistribution products. The reaction of 1-OSiMe3 with excess Ph2SiH2/Ph2SiD2 revealed a net KIE of ca. 1.3-1.4 at room temperature. Treating 1-OSiMe3 with excess Ph3SiH also gave 1-H and the corresponding disilyl ether Ph3SiOSiMe3, but this reaction also generated the new siloxide 1-OSiPh3 apparently via an unconventional sigma-bond metathesis pathway in which the Ni center is not involved directly. The reaction of excess PhSiH3 and 2-OSiMe3 gave polysilanes of varying solubilities and molecular weights; NMR investigations showed that these polymers arise from Ni(0) species generated in situ from the reductive elimination of the highly reactive hydride intermediate, 2-H. The stoichiometric reactions of 2-OSiMe3 with Ph2SiH2 and Ph3SiH gave, respectively, siloxides 2 OSiPh2(OSiMe3) and 2-OSiPh3. Together, these results demonstrate the strong influence of pincer backbone and hydrosilane sterics on the different reactivities of 1-OSiMe3 and 2-OSiMe3 toward Ph(n)SiH(4-n) (dimerization, polymerization, and redistribution vs formation of new siloxides). The mechanisms of the reactions that lead to the observed Si-O, Si-C, and Si-Si bond formations are discussed in terms of classical and unconventional sigma-bond metathesis pathways. PMID- 26562479 TI - Metal-Free Approach for the Synthesis of N-Aryl Sulfoximines via Aryne Intermediate. AB - A metal-free and operationally simple N-arylation of NH-sulfoximines with aryne precursors is reported. Transition metal-free reaction conditions and shorter reaction times are the highlights of the present method. The mild optimized condition was also found to be suitable with enantiopure substrates. PMID- 26562480 TI - Threonine532 phosphorylation in ClC-3 channels is required for angiotensin II induced Cl(-) current and migration in cultured vascular smooth muscle cells. AB - BACKGROUND AND PURPOSE: Angiotensin II (AngII) induces migration and growth of vascular smooth muscle cell (VSMC), which is responsible for vascular remodelling in some cardiovascular diseases. Ang II also activates a Cl(-) current, but the underlying mechanism is not clear. EXPERIMENTAL APPROACH: The A10 cell line and primary cultures of VSMC from control, ClC-3 channel null mice and WT mice made hypertensive with AngII infusions were used. Techniques employed included whole cell patch clamp, co-immunoprecipitation, site-specific mutagenesis and Western blotting, KEY RESULTS: In VSMC, AngII induced Cl(-) currents was carried by the chloride ion channel ClC-3. This current was absent in VSMC from ClC-3 channel null mice. The AngII-induced Cl(-) current involved interactions between ClC-3 channels and Rho-kinase 2 (ROCK2), shown by N- or C-terminal truncation of ClC-3 protein, ROCK2 siRNA and co-immunoprecipitation assays. Phosphorylation of ClC-3 channels at Thr(532) by ROCK2 was critical for AngII-induced Cl(-) current and VSMC migration. The ClC-3 T532D mutant (mutation of Thr(532) to aspartate), mimicking phosphorylated ClC-3 protein, significantly potentiated AngII-induced Cl(-) current and VSMC migration, while ClC-3 T532A (mutation of Thr(532) to alanine) had the opposite effects. AngII-induced cell migration was markedly decreased in VSMC from ClC-3 channel null mice that was insensitive to Y27632, an inhibitor of ROCK2. In addition, AngII-induced cerebrovascular remodelling was decreased in ClC-3 null mice, possibly by the ROCK2 pathway. CONCLUSIONS AND IMPLICATIONS: ClC-3 protein phosphorylation at Thr(532) by ROCK2 is required for AngII-induced Cl(-) current and VSMC migration that are involved in AngII-induced vascular remodelling in hypertension. PMID- 26562481 TI - Dimeric Octaketide Spiroketals from the Jellyfish-Derived Fungus Paecilomyces variotii J08NF-1. AB - Paeciloketals (1-3), new benzannulated spiroketal derivatives, were isolated from the marine fungus Paecilomyces variotii derived from the giant jellyfish Nemopilema nomurai. Compound 1 was present as a racemate and was resolved into enantiopure 1a and 1b by chiral-phase separation on a cellulose column. Compounds 2 and 3, possessing a novel benzannulated spiroketal skeleton, were rapidly interconvertible and yielded an equilibrium mixture on standing at room temperature. The relative and absolute configurations of compounds 2 and 3 were determined by NOESY analysis and ECD calculations. Compound 1 showed modest antibacterial activity against the marine pathogen Vibrio ichthyoenteri. PMID- 26562483 TI - When and how should patients with multiple endocrine neoplasia type 1 be screened for thymic and bronchial carcinoid tumours? AB - Patients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumours are uncommon but important manifestations of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 1-2 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate-high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, co-ordinated efforts from different stakeholders are required so that large, prospective, multicentre studies evaluating patient important outcomes are carried out. PMID- 26562484 TI - Health care utilization and costs for children and adults with duchenne muscular dystrophy. AB - INTRODUCTION: Duchenne muscular dystrophy (DMD) is an incurable neuromuscular disorder of childhood. Healthcare, caregiving, and other resource needs of affected individuals are thought to be substantial; however, the economic burden associated with DMD has not yet been assessed specifically in Australia. METHODS: Australian households with a child with DMD were asked to complete a cross sectional survey. Data were collected on annual resource utilization including hospital and medical services, equipment, home modifications, informal care, and working days lost. RESULTS: Mean healthcare costs were found to be $10,046 Australian dollars per affected individual and were markedly higher than average Australian health expenditures at each age group. The mean total cost was $46,700 (median $32,300), with healthcare costs contributing 22% of total costs. CONCLUSIONS: The annual economic cost of DMD was found to be high, reflecting a significant socioeconomic burden, especially in boys who reach adulthood, where household resource use and caregiving burden is highest. Muscle Nerve 53: 877 884, 2016. PMID- 26562482 TI - The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications. AB - The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly coordinated motion of the intestinal tract, known as motility, which is coregulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure-function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multiscale research challenges in interdisciplinary gastrointestinal sciences. PMID- 26562485 TI - Genomic resources and their influence on the detection of the signal of positive selection in genome scans. AB - Genome scans represent powerful approaches to investigate the action of natural selection on the genetic variation of natural populations and to better understand local adaptation. This is very useful, for example, in the field of conservation biology and evolutionary biology. Thanks to Next Generation Sequencing, genomic resources are growing exponentially, improving genome scan analyses in non-model species. Thousands of SNPs called using Reduced Representation Sequencing are increasingly used in genome scans. Besides, genome sequences are also becoming increasingly available, allowing better processing of short-read data, offering physical localization of variants, and improving haplotype reconstruction and data imputation. Ultimately, genome sequences are also becoming the raw material for selection inferences. Here, we discuss how the increasing availability of such genomic resources, notably genome sequences, influences the detection of signals of selection. Mainly, increasing data density and having the information of physical linkage data expand genome scans by (i) improving the overall quality of the data, (ii) helping the reconstruction of demographic history for the population studied to decrease false-positive rates and (iii) improving the statistical power of methods to detect the signal of selection. Of particular importance, the availability of a high-quality reference genome can improve the detection of the signal of selection by (i) allowing matching the potential candidate loci to linked coding regions under selection, (ii) rapidly moving the investigation to the gene and function and (iii) ensuring that the highly variable regions of the genomes that include functional genes are also investigated. For all those reasons, using reference genomes in genome scan analyses is highly recommended. PMID- 26562486 TI - Theoretical Investigation of the Radical-Radical Reaction of O((3)P) + C2H3 and Comparison with Gas-Phase Crossed-Beam Experiments. AB - Herein, we present an ab initio study of the prototypal radical-radical reactions of ground-state atomic oxygen [O((3)P)] with the vinyl (C2H3) radical using density functional theory and a complete basis set model. Two distinctive pathways on the lowest doublet potential energy surfaces (PESs) were predicted to be in competition: addition and abstraction. The barrierless addition of O((3)P) to the hydrocarbon radicals leads to energy-rich intermediate formation followed by subsequent isomerization and decomposition to yield various products: CH2CO (ketene) + H, CO + CH3, C2HOH (acetylenol) + H, (3,1)CCHOH + H, H2O + C2H, (3,1)CH2 + HCO, H2CO (formaldehyde) + CH, C2H2 (acetylene) + OH, and (3,1)CCH2 + OH. The competing but minor H-atom abstraction mechanisms produce C2H2 + OH and (1,3)CCH2 + OH. The optimized structures of the reactants, products, intermediates, and transition states and the reaction mechanisms were obtained on the lowest doublet PESs. The major pathway was predicted to be the formation of CH2CO + H through the low-barrier, single-step cleavages of the addition intermediates. The Levine-Bernstein prior method, statistical surprisal approach, and microcanonical Rice-Ramsperger-Kassel-Marcus theory were applied to deduce the energy distributions of H atoms and OH products and quantitative rate constants. On the basis of the statistical theory and the population analysis, the predicted energy distributions were compared to the kinetic energy release of H and the preferential population of the Pi(A') component of OH products reported in recent gas-phase crossed-beam investigations (Park, M. J.; Jang, S. C.; Choi, J. H. J. Chem. Phys. 2012, 137, 204311), and their kinetic and dynamic characteristics were discussed. PMID- 26562487 TI - I + (H2O)2 -> HI + (H2O)OH Forward and Reverse Reactions. CCSD(T) Studies Including Spin-Orbit Coupling. AB - The potential energy profile for the atomic iodine plus water dimer reaction I + (H2O)2 -> HI + (H2O)OH has been explored using the "Gold Standard" CCSD(T) method with quadruple-zeta correlation-consistent basis sets. The corresponding information for the reverse reaction HI + (H2O)OH -> I + (H2O)2 is also derived. Both zero-point vibrational energies (ZPVEs) and spin-orbit (SO) coupling are considered, and these notably alter the classical energetics. On the basis of the CCSD(T)/cc-pVQZ-PP results, including ZPVE and SO coupling, the forward reaction is found to be endothermic by 47.4 kcal/mol, implying a significant exothermicity for the reverse reaction. The entrance complex I...(H2O)2 is bound by 1.8 kcal/mol, and this dissociation energy is significantly affected by SO coupling. The reaction barrier lies 45.1 kcal/mol higher than the reactants. The exit complex HI...(H2O)OH is bound by 3.0 kcal/mol relative to the asymptotic limit. At every level of theory, the reverse reaction HI + (H2O)OH -> I + (H2O)2 proceeds without a barrier. Compared with the analogous water monomer reaction I + H2O -> HI + OH, the additional water molecule reduces the relative energies of the entrance stationary point, transition state, and exit complex by 3-5 kcal/mol. The I + (H2O)2 reaction is related to the valence isoelectronic bromine and chlorine reactions but is distinctly different from the F + (H2O)2 system. PMID- 26562488 TI - Effects of lead exposure on dendrite and spine development in hippocampal dentate gyrus areas of rats. AB - Lead exposure has been implicated in the impairment of synaptic plasticity in the hippocampal dentate gyrus (DG) areas of rats. However, whether the degradation of physiological properties is based on the morphological alteration of granule neurons in DG areas remains elusive. Here, we examined the dendritic branch extension and spine formation of granule neurons after lead exposure during development in rats. Dendritic morphology was studied using Golgi-Cox stain method, which was followed by Sholl analysis at postnatal days 14 and 21. Our results indicated that, for both ages, lead exposure significantly decreased the total dendritic length and spine density of granule neurons in the DG of the rat hippocampus. Further branch order analysis revealed that the decrease of dendritic length was observed only at the second branch order. Moreover, there were obvious deficits in the proportion and size of mushroom-type spines. These deficits in spine formation and maturity were accompanied by a decrease in Arc/Arg3.1 expression. Our present findings are the first to show that developmental lead exposure disturbs branch and spine formation in hippocampal DG areas. Arc/Arg3.1 may have a critical role in the disruption of neuronal morphology and synaptic plasticity in lead-exposed rats. PMID- 26562490 TI - Infrared Thermal Imaging: A Tool for Simple, Simultaneous, and High-Throughput Enthalpimetric Analysis. AB - In this work, the feasibility of infrared thermal imaging (ITI) is demonstrated to show its potential application in analytical chemistry. A system of ITI was combined with disposable microplates to perform enthalpimetric analysis, which was selected as an example in order to show the reliability of this method. In this way, the novel thermal infrared enthalpimetry (TIE) method was evaluated in neutralization, precipitation, redox, and complexation reactions, with a multichannel pipet for adding the reagent and an infrared camera to monitor the temperature of multiple reactions (up to 24 simultaneous reactions) in a contactless way. Analytical signals were obtained in only 10 s, and the difference in temperature (DeltaT) before and after the reaction was used for the construction of calibration curves by use of reference solutions. More than 10,000 values were considered for the temperature determination for each reaction. The proposed method was applied for determination of the total acidity of vinegar as well as the chloride, iron, and calcium content of pharmaceuticals. The results were compared with those from conventional techniques (titration), and agreement between 96% and 101% was obtained. Sample throughput could even reach thousands of samples analyzed in 1 h. These preliminary results demonstrate the important features of TIE and possible application for other matrices and analytical parameters. The proposed TIE could be spread to cover other enthalpimetric techniques, different reactors (e.g., microfluidic and paper analytical devices), and portable devices, thus reaching other fields of chemistry. PMID- 26562489 TI - UV Action Spectroscopy of Gas-Phase Peptide Radicals. AB - UV photodissociation (UVPD) action spectroscopy is reported to provide a sensitive tool for the detection of radical sites in gas-phase peptide ions. UVPD action spectra of peptide cation radicals of the z-type generated by electron transfer dissociation point to the presence of multiple structures formed as a result of spontaneous isomerizations by hydrogen atom migration. N-terminal Calpha radicals are identified as the dominant components, but the content of isomers differing in the radical defect position in the backbone or side chain depends on the nature of the aromatic residue with phenylalanine being more prone to isomerization than tryptophan. These results illustrate that spontaneous hydrogen atom migrations can occur in peptide cation-radicals upon electron transfer dissociation. PMID- 26562491 TI - Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term (PLEASANT): Recruiting Primary Care Research Sites-the PLEASANT experience. AB - BACKGROUND: Recruitment of general practices and their patients into research studies is frequently reported as a challenge. The Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term (PLEASANT) trial recruited 142 general practices, across England and Wales and delivered the study intervention to time and target. AIMS: To describe the process of recruitment used within the cluster randomised PLEASANT trial and present results on factors that influenced recruitment. METHODS: Data were collected on the number of and types of contact used to gain expression of interest and subsequent randomisation into the PLEASANT trial. Practice size and previous research experience were also collected. RESULTS: The mean number of contacts required to gain expression of interest were m=3.01 (s.d. 1.6) and total number of contacts from initial invitation to randomisation m=6.8 (s.d. 3.5). Previous randomised controlled trial involvement (hazard ratio (HR)=1.81 (confidence interval (CI) 95%, 1.55-2.11) P<0.001) and number of studies a practice had previously engaged in (odds ratio (OR) 1.91 (CI 95%, (1.52-2.42)) P<0.001), significantly influenced whether a practice would participate in PLEASANT. Practice size was not a significant deciding factor (OR=1.04 (95% CI 0.99-1.08) P=0.137). CONCLUSIONS: Recruitment to time and target can be achieved in general practice. The amount of resource required for site recruitment should not, however, be underestimated and multiple strategies for contacting practices should be considered. General practitioners with more research experience are more likely to participate in studies. PMID- 26562492 TI - Participatory design and validation of mobility enhancement robotic wheelchair. AB - The design of the mobility enhancement robotic wheelchair (MEBot) was based on input from electric powered wheelchair (EPW) users regarding the conditions they encounter when driving in both indoor and outdoor environments that may affect their safety and result in them becoming immobilized, tipping over, or falling out of their wheelchair. Phase I involved conducting a participatory design study to understand the conditions and barriers EPW users found to be difficult to drive in/over. Phase II consisted of creating a computer-aided design (CAD) prototype EPW to provide indoor and outdoor mobility that addressed these conditions with advanced applications. Phase III involved demonstrating the advanced applications and gathering feedback from end users about the likelihood they would use the advanced applications. The CAD prototype incorporated advanced applications, including self-leveling, curb climbing, and traction control, that addressed the challenging conditions and barriers discussed with EPW users (n = 31) during the participatory design study. Feedback of the CAD design and applications in phase III from end users (n = 12) showed a majority would use self-leveling (83%), traction control (83%), and curb climbing (75%). The overall design of MEBot received positive feedback from EPW users. However, these opinions will need to be reevaluated through user trials as the design advances. PMID- 26562493 TI - Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children. AB - Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for >=2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a study of TH. The true feasibility of such a study depends on the sample size necessary to achieve therapeutic effects on justifiable clinical outcomes. PMID- 26562494 TI - Utility of Pretest Probability and Exercise Treadmill Test in Korean Women with Suspected Coronary Artery Disease. AB - BACKGROUND: Pretest probability (PTP) and an exercise treadmill test (ETT) are recommended for the initial evaluation of possible coronary artery disease (CAD), but the applicability of these tests in Korean women has not been evaluated. METHODS: Korean women with PTP, ETT, and invasive coronary angiography results were enrolled. Across all PTP levels, PTP and ETT statistics were evaluated and independent CAD predictors obtained. RESULTS: Of the 335 patients (mean age 58.0 +/- 10.2 years), 99 and 236 were in the low (LPTP) and intermediate PTP (IPTP) groups, respectively. The observed prevalence of CAD was significantly lower than the PTP. (7.1% vs. 9.1 +/- 4.9% in LPTP, p < 0.001; 23.3% vs. 33.0 +/- 15.1% in IPTP, p < 0.001) The ETT's sensitivity and positive predictive values (PPVs) appeared lower than previously reported (LPTP: 42.9% and 16.7%; IPTP: 61.8% and 37.0%), whereas the negative predictive values (NPVs) were higher (LPTP: 95.1%; IPTP: 85.4%). After multivariate adjustments, positive ETT (odds ratio 3.276, 95% confidence interval 1.643-6.532, p = 0.001) independently predicted the presence of CAD, but the PTP showed only marginal predictability (odds ratio 1.019, 95% confidence interval 0.998-1.041, p = 0.069). CONCLUSIONS: In Korean women, the observed prevalence of CAD was lower than the PTP, and PTP showed only marginal CAD predictability. Although a positive ETT independently predicted CAD, the ETT showed lower sensitivity and PPVs than previously reported. Despite the limited value of PTP and ETT, the high NPVs of ETT appear useful for saving patients from unnecessary further examinations. PMID- 26562495 TI - Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease. AB - OBJECTIVE: An imbalance in sex hormone ratios has been identified in coronary heart disease (CHD), and as a key enzyme in the conversion of androgen to estrogen, aromatase plays an important role in the balance of sex hormone levels. However, there is a paucity of research into the potential roles of aromatase in CHD. In this study, we investigated associations between single-nucleotide polymorphisms (SNPs) in the CYP19 gene, which encodes aromatase, and CHD. METHODS: We collected 1706 blood samples from CHD patients and control participants and used propensity score matching techniques to match case and control groups with respect to confounding factors. In a final study population, including 596 individuals, we conducted a case-control study to identify associations between three SNPs in CYP19 and CHD using chi(2) or Fisher exact tests, and binary logistic regression analysis. Differences in lipid levels and parameters of echocardiography among individuals with different genotypes were assessed by one-way analysis of variance. RESULTS: The distributions of rs2289105 alleles in the CYP19 gene differed significantly between the CHD and control groups (p = 0.014), and the heterozygote CT genotype was associated with a significantly lower risk of CHD compared to the homozygous wild-type CC genotype (p = 0.0063 and odds ratio = 0.575). However, blood lipid levels and echocardiographic parameters among individuals with different genotypes did not differ between the CHD and control groups. CONCLUSIONS: The CT genotype of the rs2289105 polymorphism in the CYP19 gene is associated with a decreased risk of CHD and may be a genetic marker of protection from CHD. PMID- 26562497 TI - Proteorhodopsin Activation Is Modulated by Dynamic Changes in Internal Hydration. AB - Proteorhodopsin, a member of the microbial rhodopsin family, is a seven transmembrane alpha-helical protein that functions as a light-driven proton pump. Understanding the proton-pumping mechanism of proteorhodopsin requires intimate knowledge of the proton transfer pathway via complex hydrogen-bonding networks formed by amino acid residues and internal water molecules. Here we conducted a series of microsecond time scale molecular dynamics simulations on both the dark state and the initial photoactivated state of blue proteorhodopsin to reveal the structural basis for proton transfer with respect to protein internal hydration. A complex series of dynamic hydrogen-bonding networks involving water molecules exists, facilitated by water channels and hydration sites within proteorhodopsin. High levels of hydration were discovered at each proton transfer site-the retinal binding pocket and proton uptake and release sites-underscoring the critical participation of water molecules in the proton-pumping mechanism. Water-bridged interactions and local water channels were also observed and can potentially mediate long-distance proton transfer between each site. The most significant phenomenon is after isomerization of retinal, an increase in water flux occurs that connects the proton release group, a conserved arginine residue, and the retinal binding pocket. Our results provide a detailed description of the internal hydration of the early photointermediates in the proteorhodopsin photocycle under alkaline pH conditions. These results lay the fundamental groundwork for understanding the intimate role that hydration plays in the structure-function relationship underlying the proteorhodopsin proton-pumping mechanism, as well as providing context for the relationship of hydration in proteorhodopsin to other microbial retinal proteins. PMID- 26562496 TI - MRI reporting standard for chronic pelvic pain: consensus development. AB - AIM: To identify radiological parameters that should be reported on gynaecological MRI in order to create a standardized assessment pro forma for reporting CPP, which may be used in clinical practice. METHODS: Chronic pelvic pain (CPP) in females is a common problem presenting a major challenge to healthcare providers. The complex multifactorial aetiology requires a multidisciplinary approach and often necessitates diagnostic laparoscopy for assessment. MRI is emerging as a potential non-invasive alternative for evaluation of CPP; however, standardization of reporting is required for it to be used in routine clinical practice. A two-generational Delphi survey with an expert panel of 28 radiologists specializing in gynaecological MRI from across the UK was used to refine a proposed reporting template for CPP. RESULTS: 75% response rate for the first round and 79% for the second. Following the second round, agreement was reached on the structure of the pro forma and the way in which information was sought, with overall consistency of agreement between experts deemed as fair (intraclass correlation coefficient = 0.394). This was accepted as the final version by consensus. CONCLUSION: The standardized pro forma developed in this study will form the basis for future prospective evaluation of MRI in CPP. This template could be modified for the assessment of other benign gynaecological conditions. ADVANCES IN KNOWLEDGE: Female CPP is a significant problem presenting challenges for clinicians. MRI is often used for evaluation and standardization of techniques, and reporting is required. The pro forma developed in this study will form the basis for future prospective MRI evaluation. PMID- 26562498 TI - Could omega-3 fatty acids improve quality of life in cancer patients? PMID- 26562500 TI - From cellulose fibrils to single chains: understanding cellulose dissolution in ionic liquids. AB - Cellulose is the most abundant and renewable organic compound on Earth, it is however not soluble in common organic solvents and aqueous solutions. Cellulose dissolution is a key aspect to promote its value-added applications. Ionic liquids (ILs) have been shown to solubilize cellulose under relatively mild conditions. The easy processability of cellulose with ILs and their environmental friendly nature prompted research in various fields such as biomass pretreatment and conversion, cellulose fiber and composite production, and chemical conversion of cellulose in ILs. Progress has been made on understanding the mechanism of cellulose dissolution in ILs, including the structural characteristics of ILs that are cellulose solvents, however many details remain unknown. In light of rapid development and importance of cellulose dissolution in the field of IL based cellulose and biomass processing, it is necessary to provide an overview of current understanding of cellulose dissolution in ILs and outline possible future research trends. Recent literature studies suggest that synergistic effects between the anions and the cations of ILs need to be revealed, which requires refining the structure of cellulose elementary fibrils, simulation of more realistic cellulose fibrils and detailed studies on the solution structure of cellulose in ILs. After analyzing literature studies, three interacting modules are identified, which are crucial to understand the process of cellulose dissolution in ILs: (1) the structure of elementary fibrils; (2) solvation of cellulose in ILs; and (3) solution structure of cellulose solubilized in ILs. A coherent analysis of these modules will aid in better design of more efficient ILs and processes. PMID- 26562499 TI - A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease. AB - In this study, we sought to develop a nonhuman primate model of pulmonary Mycobacterium avium complex (MAC) disease. Blood and bronchoalveolar lavage fluid were collected from three female rhesus macaques infected intrabronchially with escalating doses of M. avium subsp. hominissuis. Immunity was determined by measuring cytokine levels, lymphocyte proliferation, and antigen-specific responses. Disease progression was monitored clinically and microbiologically with serial thoracic radiographs, computed tomography scans, and quantitative mycobacterial cultures. The animal subjected to the highest inoculum showed evidence of chronic pulmonary MAC disease. Therefore, rhesus macaques could provide a robust model in which to investigate host-pathogen interactions during MAC infection. PMID- 26562501 TI - [Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation]. AB - In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation. PMID- 26562502 TI - Evaluation of Frequency-Doubling Technology Perimetry as a Means of Screening for Glaucoma and Other Eye Diseases Using the National Health and Nutrition Examination Survey. AB - IMPORTANCE: Glaucoma is a significant cause of global blindness and there are, as yet, no effective means of screening. OBJECTIVE: To assess the potential role of frequency-doubling technology (FDT) perimetry in screening for glaucoma using data collected as part of the National Health and Nutrition Examination Survey (NHANES). DESIGN, SETTING, AND PARTICIPANTS: Reanalysis of cross-sectional data of 6797 participants in the 2005-2008 cycles of the NHANES, which evaluated a sample of the noninstitutionalized US population with at least light-perception vision. A subset of optic nerve photographs were regraded by 3 glaucoma specialists in December 2012. Each participant underwent visual field testing, including FDT perimetry screening, and had fundus photographs taken. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of FDT perimetry to detect glaucoma, macular disease, or decreased visual acuity. RESULTS: A total of 5746 NHANES participants had optic images originally graded. We regraded 1201 images of 1073 eyes of 548 participants with initial cup-disc ratio (CDR) of 0.6 or greater and 423 images of 360 eyes of 180 randomly selected participants with initial CDR less than 0.6. Diagnoses of glaucoma by disc photograph were 1.6% (3 of 180) in the CDR less than 0.6 group and 31.4% (172 of 548) in the CDR of 0.6 or greater group. The sensitivity of FDT was 33% (95% CI, 0%-87%) and specificity was 77% (95% CI, 71%-84%). For the group with at least 1 CDR of 0.6 or greater, sensitivity of FDT was 66% (95% CI, 59%-73%) and specificity was 70% (95% CI, 66% 75%). When analyzed to give FDT credit for identifying glaucoma, macular disease, or decreased visual acuity, the sensitivity of the test was 80% (95% CI, 77%-83%) and the specificity was 83% (95% CI, 82%-84%). Approximately 25% of the NHANES population was not able to successfully complete FDT testing, representing screening failures and decreasing specificity. CONCLUSIONS AND RELEVANCE: Using the 2005-2008 waves of the NHANES as a model of population-based screening for eye disease, FDT perimetry lacks both sensitivity and specificity as a means of screening for glaucoma, the presence of retinal disease, or decreased acuity in a population-based setting. Given that no single test of glaucoma has yet been shown to be appropriate in a screening setting, to our knowledge, investigators should consider novel methods of detecting glaucoma or combinations of tests that might work better in a screening setting. PMID- 26562503 TI - PD-L1 Testing in Cancer: Challenges in Companion Diagnostic Development. PMID- 26562504 TI - Multidrug-Resistant Escherichia coli Strains Isolated from Patients Are Associated with Class 1 and 2 Integrons. AB - BACKGROUND: Escherichia coli isolates displaying multidrug-resistance (MDR) are a major health care problem that results in mortality and morbidity. Integrons are DNA elements in E.coli that are related to antibiotic resistance. The aim of this study was to determine class 1 and 2 integrons and MDR in E. coli isolates obtained from patients in two Sanandaj hospitals, located in Iran. MATERIALS AND METHODS: 120 isolates of E. coli were obtained from clinical specimens (from November 2013 to April 2014), and the susceptibility of E. coli antimicrobial agents was determined using the Kirby-Bauer disk diffusion method according to the CLSI. PCR were applied for detection of class 1 and 2 integrons in E. coli isolates. SPSS software v16 and the x03C7;2 test were used for statistical analysis in order to calculate the association between antibiotic resistance and the presence of integrons (p < 0.05). RESULTS: In a total of 120 E. coli isolates, 42.5% had MDR. Integrons were found in 50.9% of the MDR isolates, and included 47.05% class 1 and 3.92% class 2 integrons. The strains did not have both classes of integrons simultaneously. An association between resistance to antibiotics and integrons was found. CONCLUSION: Our results showed that int1 and int2 genes present in E. coli isolates obtained from patients cause MDR in this isolates. Since such bacteria are a reservoir for the transmission of MDR bacteria, appropriate programs are necessary to reduce this problem. PMID- 26562505 TI - A Substrate Mimic Allows High-Throughput Assay of the FabA Protein and Consequently the Identification of a Novel Inhibitor of Pseudomonas aeruginosa FabA. AB - Eukaryotes and prokaryotes possess fatty acid synthase (FAS) biosynthetic pathways that comprise iterative chain elongation, reduction, and dehydration reactions. The bacterial FASII pathway differs significantly from human FAS pathways and is a long-standing target for antibiotic development against Gram negative bacteria due to differences from the human FAS, and several existing antibacterial agents are known to inhibit FASII enzymes. N-Acetylcysteamine (NAC) fatty acid thioesters have been used as mimics of the natural acyl carrier protein pathway intermediates to assay FASII enzymes, and we now report an assay of FabV from Pseudomonas aeruginosa using (E)-2-decenoyl-NAC. In addition, we have converted an existing UV absorbance assay for FabA, the bifunctional dehydration/epimerization enzyme and key target in the FASII pathway, into a high throughput enzyme coupled fluorescence assay that has been employed to screen a library of diverse small molecules. With this approach, N-(4-chlorobenzyl)-3-(2 furyl)-1H-1,2,4-triazol-5-amine (N42FTA) was found to competitively inhibit (pIC50=5.7+/-0.2) the processing of 3-hydroxydecanoyl-NAC by P. aeruginosa FabA. N42FTA was shown to be potent in blocking crosslinking of Escherichia coli acyl carrier protein and FabA, a direct mimic of the biological process. The co complex structure of N42FTA with P. aeruginosa FabA protein rationalises affinity and suggests future design opportunities. Employing NAC fatty acid mimics to develop further high-throughput assays for individual enzymes in the FASII pathway should aid in the discovery of new antimicrobials. PMID- 26562506 TI - Structural Stability and Local Dynamics in Disease-Causing Mutants of Human Apolipoprotein A-I: What Makes the Protein Amyloidogenic? AB - ApoA-I, the major protein of plasma high-density lipoprotein, removes cellular cholesterol and protects against atherosclerosis. ApoA-I mutations can cause familial amyloidosis, a life-threatening disease wherein N-terminal protein fragments form fibrils in vital organs. To unveil the protein misfolding mechanism and to understand why some mutations cause amyloidosis while others do not, we analyzed the structure, stability, and lipid-binding properties of naturally occurring mutants of full-length human apoA-I causing either amyloidosis (G26R, W50R, F71Y, and L170P) or aberrant lipid metabolism (L159R). Global and local protein conformation and dynamics in solution were assessed by circular dichroism, fluorescence, and hydrogen-deuterium exchange mass spectrometry. All mutants showed increased deuteration in residues 14-22, supporting our hypothesis that decreased protection of this major amyloid "hot spot" can trigger protein misfolding. In addition, L159R showed local helical unfolding near the mutation site, consistent with cleavage of this mutant in plasma to generate the labile 1-159 fragment. Together, the results suggest that reduced protection of the major amyloid "hot spot", combined with the structural integrity of the native helix bundle conformation, shifts the balance from protein clearance to beta-aggregation. A delicate balance between the overall structural integrity of a globular protein and the local destabilization of its amyloidogenic segments may be a fundamental determinant of this and other amyloid diseases. Furthermore, mutation-induced conformational changes observed in the helix bundle, which comprises the N-terminal 75% of apoA-I, and its flexible C terminal tail suggest the propagation of structural perturbations to distant sites via an unexpected template-induced ensemble-based mechanism, challenging the classical structure-based view. PMID- 26562508 TI - Correction: SOX9 Regulates Multiple Genes in Chondrocytes, Including Genes Encoding ECM Proteins, ECM Modification Enzymes, Receptors, and Transporters. PMID- 26562507 TI - Neuromechanistic Model of Auditory Bistability. AB - Sequences of higher frequency A and lower frequency B tones repeating in an ABA- triplet pattern are widely used to study auditory streaming. One may experience either an integrated percept, a single ABA-ABA- stream, or a segregated percept, separate but simultaneous streams A-A-A-A- and -B---B--. During minutes-long presentations, subjects may report irregular alternations between these interpretations. We combine neuromechanistic modeling and psychoacoustic experiments to study these persistent alternations and to characterize the effects of manipulating stimulus parameters. Unlike many phenomenological models with abstract, percept-specific competition and fixed inputs, our network model comprises neuronal units with sensory feature dependent inputs that mimic the pulsatile-like A1 responses to tones in the ABA- triplets. It embodies a neuronal computation for percept competition thought to occur beyond primary auditory cortex (A1). Mutual inhibition, adaptation and noise are implemented. We include slow NDMA recurrent excitation for local temporal memory that enables linkage across sound gaps from one triplet to the next. Percepts in our model are identified in the firing patterns of the neuronal units. We predict with the model that manipulations of the frequency difference between tones A and B should affect the dominance durations of the stronger percept, the one dominant a larger fraction of time, more than those of the weaker percept-a property that has been previously established and generalized across several visual bistable paradigms. We confirm the qualitative prediction with our psychoacoustic experiments and use the behavioral data to further constrain and improve the model, achieving quantitative agreement between experimental and modeling results. Our work and model provide a platform that can be extended to consider other stimulus conditions, including the effects of context and volition. PMID- 26562512 TI - Hemispheric Retinal Arteriovenous Anastomoses: (Wyburn-Mason Syndrome). PMID- 26562513 TI - Polypoidal Choroidal Vasculopathy: Imaging by Indocyanine Green Angiography and En Face Optical Coherence Tomography. PMID- 26562509 TI - Axial Diffusivity of the Corona Radiata at 24 Hours Post-Stroke: A New Biomarker for Motor and Global Outcome. AB - Fractional anisotropy (FA) is an effective marker of motor outcome at the chronic stage of stroke yet proves to be less efficient at early time points. This study aims to determine which diffusion metric in which location is the best marker of long-term stroke outcome after thrombolysis with diffusion tensor imaging (DTI) at 24 hours post-stroke. Twenty-eight thrombolyzed patients underwent DTI at 24 hours post-stroke onset. Ipsilesional and contralesional FA, mean (MD), axial (AD), and radial (RD) diffusivities values were calculated in different Regions of-Interest (ROIs): (1) the white matter underlying the precentral gyrus (M1), (2) the corona radiata (CoRad), (3) the posterior limb of the internal capsule (PLIC) and (4) the cerebral peduncles (CP). NIHSS scores were acquired at admission, day 1, and day 7; modified Rankin Scores (mRS) at 3 months. Significant decreases were found in FA, MD, and AD of the ipsilesional CoRad and M1. MD and AD were also significantly lower in the PLIC. The ratio of ipsi and contralesional AD of the CoRad (CoRad-rAD) was the strongest diffusion parameter correlated with motor NIHSS scores on day 7 and with the mRS at 3 months. A Receiver-Operator Curve analysis yielded a model for the CoRad-rAD to predict good outcome based on upper limb NIHSS motor scores and mRS with high specificity and sensitivity. FA values were not correlated with clinical outcome. In conclusion, axial diffusivity of the CoRad from clinical DTI at 24 hours post stroke is the most appropriate diffusion metric for quantifying stroke damage to predict outcome, suggesting the importance of early axonal damage. PMID- 26562514 TI - Enhanced Depth Imaging Optical Coherence Tomography of Endogenous Fungal Chorioretinitis. PMID- 26562515 TI - Myopic Cleavage of Retinal Nerve Fiber Layer Assessed by Split-Spectrum Amplitude Decorrelation Angiography Optical Coherence Tomography. PMID- 26562516 TI - The Cascade of Care for an Australian Community-Based Hepatitis C Treatment Service. AB - BACKGROUND: Hepatitis C treatment uptake in Australia is low. To increase access to hepatitis C virus treatment for people who inject drugs, we developed a community-based, nurse-led service that linked a viral hepatitis service in a tertiary hospital to primary care clinics, and resulted in hepatitis C treatment provision in the community. METHODS: A retrospective cohort study of patients referred to the community hepatitis service was undertaken to determine the cascade of care. Logistic regression analyses were used to identify predictors of hepatitis C treatment uptake. RESULTS: Four hundred and sixty-two patients were referred to the community hepatitis service; 344 attended. Among the 279 attendees with confirmed chronic hepatitis C, 257 (99%) reported ever injecting drugs, and 124 (48%) injected in the last month. Of 201 (72%) patients who had their fibrosis staged, 63 (31%) had F3-F4 fibrosis. Fifty-five patients commenced hepatitis C treatment; 26 (47%) were current injectors and 25 (45%) had F3-F4 fibrosis. Nineteen of the 27 (70%) genotype 1 patients and 14 of the 26 (54%) genotype 3 patients eligible for assessment achieved a sustained virologic response. Advanced fibrosis was a significant predictor of treatment uptake in adjusted analysis (AOR 2.56, CI 1.30-5.00, p = 0.006). CONCLUSIONS: Our community hepatitis service produced relatively high rates of fibrosis assessment, hepatitis C treatment uptake and cure, among people who inject drugs. These findings highlight the potential benefits of providing community-based hepatitis C care to people who inject drugs in Australia-benefits that should be realised as direct-acting antiviral agents become available. PMID- 26562517 TI - Performance of Droplet Digital PCR in Non-Invasive Fetal RHD Genotyping - Comparison with a Routine Real-Time PCR Based Approach. AB - Detection and characterization of circulating cell-free fetal DNA (cffDNA) from maternal circulation requires an extremely sensitive and precise method due to very low cffDNA concentration. In our study, droplet digital PCR (ddPCR) was implemented for fetal RHD genotyping from maternal plasma to compare this new quantification alternative with real-time PCR (qPCR) as a golden standard for quantitative analysis of cffDNA. In the first stage of study, a DNA quantification standard was used. Clinical samples, including 10 non-pregnant and 35 pregnant women, were analyzed as a next step. Both methods' performance parameters-standard curve linearity, detection limit and measurement precision were evaluated. ddPCR in comparison with qPCR has demonstrated sufficient sensitivity for analysing of cffDNA and determination of fetal RhD status from maternal circulation, results of both methods strongly correlated. Despite the more demanding workflow, ddPCR was found to be slightly more precise technology, as evaluated using quantitative standard. Regarding the clinical samples, the precision of both methods equalized with decreasing concentrations of tested DNA samples. In case of cffDNA with very low concentrations, variance parameters of both techniques were comparable. Detected levels of fetal cfDNA in maternal plasma were slightly higher than expected and correlated significantly with gestational age as measured by both methods (ddPCR r = 0.459; qPCR r = 0.438). PMID- 26562518 TI - Seeing the Big Picture: Size Perception Is More Context Sensitive in the Presence of Others. AB - This paper tests the hypothesis that social presence influences size perception by increasing context sensitivity. Consistent with Allport's prediction, we expected to find greater context sensitivity in participants who perform a visual task in the presence of other people (i.e., in co-action) than in participants who perform the task in isolation. Supporting this hypothesis, participants performing an Ebbinghaus illusion-based task in co-action showed greater size illusions than those performing the task in isolation. Specifically, participants in a social context had greater difficulty perceiving the correct size of a target circle and ignoring its surroundings. Analyses of delta plot functions suggest a mechanism of interference monitoring, since that when individuals take longer to respond, they are better able to ignore the surrounding circles. However, this type of monitoring interference was not moderated by social presence. We discuss how this lack of moderation might be the reason why the impact of social presence on context sensitivity is able to be detected in tasks such as the Ebbinghaus illusion. PMID- 26562519 TI - Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats. AB - Many studies have demonstrated the key role of lysosomes in ischemic cell death in the brain and have led to the "lysosomocentric" hypothesis. In this hypothesis, the release of cathepsin-B due to a change of lysosomal membrane permeabilization (LMP) or rupture is critical, and this can be prevented by its inhibitors CA074 and CA074-me. However, the role of CA074-me in neuronal death and its effect on the change of lysosomal membrane integrity after global cerebral ischemia/reperfusion (I/R) injury is not clear, so we investigated this here. Rat hippocampal CA1 neuronal death was evaluated after 20-min global cerebral I/R injury. CA074-me (1 MUg, 10 MUg) were given intracerebroventricularly 1h before ischemia or 1h post reperfusion. The changes of heat shock protein 70 (Hsp70), cathepsin-B, lysosomal-associated membrane protein 1 (LAMP-1), receptor-interacting protein 3 (RIP3), and the change of lysosomal pH were evaluated respectively. Hippocampal CA1 neuronal programmed necrosis induced by global cerebral I/R injury was prevented by CA074-me both pre treatment and post-treatment. Diffuse cytoplasmic cathepsin-B and LAMP-1 immunostaining synchronized with the pyknotic nuclear changes 2 days post reperfusion, and a rise of lysosomal pH with the leakage of DND-153, a dye of lysosomes, after oxygen-glucose deprivation (OGD) was detected. Both of these changes demonstrated the rupture of lysosomal membrane and the leakage of cathepsin-B, and this was strongly inhibited by CA074-me pre-treatment. The overexpression and nuclear translocation of RIP3 and the reduction of NAD(+) level after I/R injury were also inhibited, while the upregulation of Hsp70 was strengthened by CA074-me pre-treatment. Delayed fulminant leakage of cathepsin-B due to lysosomal rupture is a critical harmful factor in neuronal programmed necrosis induced by 20-min global I/R injury. In addition to being an inhibitor of cathepsin-B, CA074-me may have an indirect neuroprotective effect by maintaining lysosomal membrane integrity and protecting against lysosomal rupture. PMID- 26562522 TI - System model enabling fast tomographic phase microscopy with total variation regularisation. AB - Tomographic phase microscopy (TPM) facilitates three-dimensional imaging of live cells based on quantitative measurement of the distribution of the refractive index, but without the need for specific staining. However, the limited imaging speed and the anisotropic resolution of the reconstructed refractive index map remain major obstacles to the extension and further application of TPM. To address these obstacles, we first formulate a general measurement model that linearises the relationship between the measurement data and refractive index map based on a system matrix. In this way, the measurement system is interpreted as a linear system in a complete manner. Then we propose a reconstruction framework for retrieving the refractive index map from the measurement data with reduced angular sample frequency and limited angular coverage of illumination. The framework aims to transform the reconstruction task into an optimisation scheme based on total variation norm regularisation, followed by an efficient solution using the accelerated alternating direction method of multipliers algorithm. Using this method, only sparse angular illuminations need to be collected, thus speeding up the imaging process. We obtained experimental results from both cell mimic phantom data and real measurement data, which showed that the proposed method can improve the imaging speed while still providing refractive index images with better quality compared with a conventional reconstruction method. PMID- 26562520 TI - Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking. AB - Chronic exposure to drugs and alcohol leads to damage to dopaminergic neurons and their projections in the 'reward pathway' that originate in the ventral tegmental area (VTA) and terminate in the nucleus accumbens (NAc). This damage is thought to contribute to the signature symptom of addiction: chronic relapse. In this study we show that bilateral transplants of human retinal pigment epithelial cells (RPECs), a cell mediated dopaminergic and trophic neuromodulator, into the medial shell of the NAc, rescue rats with a history of high rates of cocaine self administration from drug-seeking when returned, after 2 weeks of abstinence, to the drug-associated chamber under extinction conditions (i.e., with no drug available). Excellent survival was noted for the transplant of RPECs in the shell and/or the core of the NAc bilaterally in all rats that showed behavioral recovery from cocaine seeking. Design based unbiased stereology of tyrosine hydroxylase (TH) positive cell bodies in the VTA showed better preservation (p<0.035) in transplanted animals compared to control animals. This experiment shows that the RPEC graft provides beneficial effects to prevent drug seeking in drug addiction via its effects directly on the NAc and its neural network with the VTA. PMID- 26562521 TI - Quality of Sterile Male Tsetse after Long Distance Transport as Chilled, Irradiated Pupae. AB - BACKGROUND: Tsetse flies transmit trypanosomes that cause human and African animal trypanosomosis, a debilitating disease of humans (sleeping sickness) and livestock (nagana). An area-wide integrated pest management campaign against Glossina palpalis gambiensis has been implemented in Senegal since 2010 that includes a sterile insect technique (SIT) component. The SIT can only be successful when the sterile males that are destined for release have a flight ability, survival and competitiveness that are as close as possible to that of their wild male counterparts. METHODOLOGY/PRINCIPAL FINDINGS: Tests were developed to assess the quality of G. p. gambiensis males that emerged from pupae that were produced and irradiated in Burkina Faso and Slovakia (irradiation done in Seibersdorf, Austria) and transported weekly under chilled conditions to Dakar, Senegal. For each consignment a sample of 50 pupae was used for a quality control test (QC group). To assess flight ability, the pupae were put in a cylinder filtering emerged flies that were able to escape the cylinder. The survival of these flyers was thereafter monitored under stress conditions (without feeding). Remaining pupae were emerged and released in the target area of the eradication programme (RF group). The following parameter values were obtained for the QC flies: average emergence rate more than 69%, median survival of 6 days, and average flight ability of more than 35%. The quality protocol was a good proxy of fly quality, explaining a large part of the variances of the examined parameters. CONCLUSIONS/SIGNIFICANCE: The quality protocol described here will allow the accurate monitoring of the quality of shipped sterile male tsetse used in operational eradication programmes in the framework of the Pan African Tsetse and Trypanosomosis Eradication Campaign. PMID- 26562523 TI - Atomic Force Microscopy Characterization of Protein Fibrils Formed by the Amyloidogenic Region of the Bacterial Protein MinE on Mica and a Supported Lipid Bilayer. AB - Amyloid fibrils play a crucial role in many human diseases and are found to function in a range of physiological processes from bacteria to human. They have also been gaining importance in nanotechnology applications. Understanding the mechanisms behind amyloid formation can help develop strategies towards the prevention of fibrillation processes or create new technological applications. It is thus essential to observe the structures of amyloids and their self-assembly processes at the nanometer-scale resolution under physiological conditions. In this work, we used highly force-sensitive frequency-modulation atomic force microscopy (FM-AFM) to characterize the fibril structures formed by the N terminal domain of a bacterial division protein MinE in solution. The approach enables us to investigate the fibril morphology and protofibril organization over time progression and in response to changes in ionic strength, molecular crowding, and upon association with different substrate surfaces. In addition to comparison of the fibril structure and behavior of MinE1-31 under varying conditions, the study also broadens our understanding of the versatile behavior of amyloid-substrate surface interactions. PMID- 26562524 TI - Comparative Study of SSVEP- and P300-Based Models for the Telepresence Control of Humanoid Robots. AB - In this paper, we evaluate the control performance of SSVEP (steady-state visual evoked potential)- and P300-based models using Cerebot-a mind-controlled humanoid robot platform. Seven subjects with diverse experience participated in experiments concerning the open-loop and closed-loop control of a humanoid robot via brain signals. The visual stimuli of both the SSVEP- and P300- based models were implemented on a LCD computer monitor with a refresh frequency of 60 Hz. Considering the operation safety, we set the classification accuracy of a model over 90.0% as the most important mandatory for the telepresence control of the humanoid robot. The open-loop experiments demonstrated that the SSVEP model with at most four stimulus targets achieved the average accurate rate about 90%, whereas the P300 model with the six or more stimulus targets under five repetitions per trial was able to achieve the accurate rates over 90.0%. Therefore, the four SSVEP stimuli were used to control four types of robot behavior; while the six P300 stimuli were chosen to control six types of robot behavior. Both of the 4-class SSVEP and 6-class P300 models achieved the average success rates of 90.3% and 91.3%, the average response times of 3.65 s and 6.6 s, and the average information transfer rates (ITR) of 24.7 bits/min 18.8 bits/min, respectively. The closed-loop experiments addressed the telepresence control of the robot; the objective was to cause the robot to walk along a white lane marked in an office environment using live video feedback. Comparative studies reveal that the SSVEP model yielded faster response to the subject's mental activity with less reliance on channel selection, whereas the P300 model was found to be suitable for more classifiable targets and required less training. To conclude, we discuss the existing SSVEP and P300 models for the control of humanoid robots, including the models proposed in this paper. PMID- 26562525 TI - Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells. AB - Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8 LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs. PMID- 26562526 TI - A novel JAK-STAT inhibitor, 2-[(3-Carbamoyl-2-thienyl)amino]-2-oxoethyl(2,6 dichlorophenyl)acetate, suppresses helper T cell differentiation in vitro and collagen-induced arthritis in vivo. AB - Th17 cells, which have been implicated in autoimmune diseases including rheumatoid arthritis (RA), require the JAK-STAT3 pathway for their differentiation and functions. Recently, JAK inhibitors have been developed as a therapeutic drug for RA. However, the current JAK inhibitors are not optimized to STAT3 compared with other STATs. In this study, we found a new lead compound of a small molecule JAK-STAT inhibitor, 2-[(3-Carbamoyl-2-thienyl)amino]-2-oxoethyl (2,6-dichlorophenyl)acetate, which inhibits STAT3 as efficiently as other STATs. This compound, named JI069, was selected by STAT3 reporter assay in combination with an in silico docking model. JI069 inhibited gp130 signaling by inducing dissociation between gp130 and JAK1. In HEK293T cells and primary T cells, JI069 suppressed STAT3 activation as efficiently as other STATs, including STAT1, STAT5, and STAT6. JI069 effectively suppressed Th1, Th2, and Th17 differentiation while strongly promoted iTreg differentiation. JI069 suppressed symptoms of the collagen-induced arthritis (CIA) model in mice, and inhibited the cytokine production from T cells as well as the STAT3 phosphorylation of synovial cells. These data suggest that JI069 is a new type of JAK inhibitor which has potential for the treatment of immunological disorders. PMID- 26562527 TI - Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia. AB - Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetes complication liver fibrosis. PMID- 26562528 TI - Identification of Ligustrum lucidum pollen allergens using a proteomics approach. AB - BACKGROUND: Ligustrum spp. are members of the Oleaceae family, one of the most prominent allergic families worldwide. The genus Ligustrum contains approximately fifty species, including Ligustrum lucidum, which have been widely cultivated as ornamental plants, and its pollen is a source of inhalant allergens associated with respiratory allergic diseases. Little is known about the presence of allergenic proteins in L. lucidum. METHODS: The L. lucidum pollen proteins were extracted by a modified phenolic extraction method. A pool of four sera from mono sensitive patients was analyzed by 2DE immunoblotting and mass spectrometric analysis was performed on 6 immunoreactive protein spots. RESULTS: SDS-PAGE of L. lucidum pollen extract revealed proteins in ranges of 15-150 kDa. The 2DE gel profile of the L. lucidum pollen protein extract showed approximately 180 spots, and the 2DE immunoblots obtained using sera from Ligustrum monosensitive patients as the source of IgE antibodies revealed six allergen protein spots, corresponding to Profilin, Enolase, Fra e 9.01 (beta-1,3-glucanase), Pollen specific Polygalacturonases, Alanine aminotransferase, and two ATP synthase beta subunits. CONCLUSION: We report for the first time the identification of IgE reactive proteins from L. lucidum. PMID- 26562529 TI - Down-regulation of the miR-543 alleviates insulin resistance through targeting the SIRT1. AB - Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin resistant HepG2 cells induced by TNF-alpha. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR 543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3beta. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension. PMID- 26562532 TI - Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism. AB - OBJECTIVE: The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. METHODS: Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. RESULTS: Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. CONCLUSION: As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. TRIAL REGISTRATION: clinicaltrials.gov NCT01633762. PMID- 26562533 TI - Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria. AB - There is significant evidence that brain-infiltrating CD8+ T cells play a central role in the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the mechanisms through which they mediate their pathogenic activity during malaria infection remain poorly understood. Utilizing intravital two-photon microscopy combined with detailed ex vivo flow cytometric analysis, we show that brain-infiltrating T cells accumulate within the perivascular spaces of brains of mice infected with both ECM-inducing (P. berghei ANKA) and non-inducing (P. berghei NK65) infections. However, perivascular T cells displayed an arrested behavior specifically during P. berghei ANKA infection, despite the brain-accumulating CD8+ T cells exhibiting comparable activation phenotypes during both infections. We observed T cells forming long-term cognate interactions with CX3CR1-bearing antigen presenting cells within the brains during P. berghei ANKA infection, but abrogation of this interaction by targeted depletion of the APC cells failed to prevent ECM development. Pathogenic CD8+ T cells were found to colocalize with rare apoptotic cells expressing CD31, a marker of endothelial cells, within the brain during ECM. However, cellular apoptosis was a rare event and did not result in loss of cerebral vasculature or correspond with the extensive disruption to its integrity observed during ECM. In summary, our data show that the arrest of T cells in the perivascular compartments of the brain is a unique signature of ECM-inducing malaria infection and implies an important role for this event in the development of the ECM-syndrome. PMID- 26562535 TI - Left persistent superior vena cava as a source of focal atrial arrhythmias: A late arrhythmia recurrence due to a latent proximal focus. PMID- 26562534 TI - High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma. AB - PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit. PMID- 26562536 TI - Mild anemia as a possible cause of false positive stress echocardiography in non obstructive coronary artery disease: A pathophysiologic hypothesis. PMID- 26562538 TI - Ni2+-Dependent and PsaR-Mediated Regulation of the Virulence Genes pcpA, psaBCA, and prtA in Streptococcus pneumoniae. AB - Previous studies have shown that the transcriptional regulator PsaR regulates the expression of the PsaR regulon consisting of genes encoding choline binding protein (PcpA), the extracellular serine protease (PrtA), and the Mn2+-uptake system (PsaBCA), in the presence of manganese (Mn2+), zinc (Zn2+), and cobalt (Co2+). In this study, we explore the Ni2+-dependent regulation of the PsaR regulon. We have demonstrated by qRT-PCR analysis, metal accumulation assays, beta-galactosidase assays, and electrophoretic mobility shift assays that an elevated concentration of Ni2+ leads to strong induction of the PsaR regulon. Our ICP-MS data show that the Ni2+-dependent expression of the PsaR regulon is directly linked to high, cell-associated, concentration of Ni2+, which reduces the cell-associated concentration of Mn2+. In vitro studies with the purified PsaR protein showed that Ni2+ diminishes the Mn2+-dependent interaction of PsaR to the promoter regions of its target genes, confirming an opposite effect of Mn2+ and Ni2+ in the regulation of the PsaR regulon. Additionally, the Ni2+ dependent role of PsaR in the regulation of the PsaR regulon was studied by transcriptome analysis. PMID- 26562539 TI - Allosteric sites: remote control in regulation of protein activity. AB - The presence of multiple allosteric sites in proteins motivates development of allosteric drugs-modulators of protein activity with potentially higher specificity and less toxicity than traditional orthosteric compounds. A quest for allosteric control of any protein starts from the identification and characterization of allosteric sites. Protein dynamics is the basis for allosteric communication. Binding of effector molecules to allosteric sites modulates structural dynamics, thus affecting activity of remote functional sites. We review here theoretical concepts and experimental approaches for exploring allosteric sites, their role in allosteric regulation, and ways to assess their druggability. Key steps of the design procedure aimed at obtaining allosteric drugs with required agonistic/antagonistic effect are proposed, and their computational and experimental elements are discussed. PMID- 26562537 TI - Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway. AB - Interleukin-17A (IL-17A) is generally considered as one of the pathogenic factors involved in multiple sclerosis (MS). Indirect evidence for this is that IL-17A producing T helper 17 (Th17) cells preferentially accumulate in lesions of MS and experimental autoimmune encephalomyelitis (EAE). However, a direct involvement of IL-17A in MS pathogenesis is still an open question. In this study, we overexpressed IL-17A in the brains of mice (IL-17A-in-Brain mice) via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated gene delivery. In spite of high levels of IL-17A expression in the brain and blood, IL-17A-in-Brain mice exhibit no inflammatory responses and no abnormalities in motor coordination and spatial orientation. Unexpectedly, IL-17A-in-Brain mice show decreases in body weight and adipose tissue mass and an improvement in glucose tolerance and insulin sensitivity. IL-17A enhances glucose uptake in PC12 cells by activation of AKT. Our results provide direct evidence for the first time that IL-17A overexpression in the central nervous system does not cause physical and learning disabilities and neuroinflammation and suggest that IL-17A may regulate glucose metabolism through the AKT signaling pathway. PMID- 26562541 TI - Hybrid triazoles: Design and synthesis as potential dual inhibitor of growth and efflux inhibition in tuberculosis. AB - Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (EI) have been tested with encouraging results as an adjuvant therapy for treatment of tuberculosis (TB). Although, EI have emerged as innovative approach of treatment for multi drug resistant (MDR) & extensively drug resistant tuberculosis (XDR TB), toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known EI and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known EI. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of TB initially against Mycobacterium smegmatis mc(2)155. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 144, 145, 154 and 163 were then tested for their GEI action against Mycobacterium tuberculosis (Mtb). Synthesized compounds were also tested for their synergistic action with first line and second line anti-TB drugs and ethidium bromide (EtBr). We arrived at compound 135 as most potent dual inhibitor of tuberculosis. PMID- 26562540 TI - Fetal Stomach Position Predicts Neonatal Outcomes in Isolated Left-Sided Congenital Diaphragmatic Hernia. AB - INTRODUCTION: We sought to determine the relationship between the degree of stomach herniation by antenatal sonography and neonatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: We retrospectively reviewed neonatal medical records and antenatal sonography of fetuses with isolated left CDH cared for at a single institution (2000-2012). Fetal stomach position was classified on sonography as follows: intra-abdominal, anterior left chest, mid-to-posterior left chest, or retrocardiac (right chest). RESULTS: Ninety fetuses were included with 70% surviving to neonatal discharge. Stomach position was intra-abdominal in 14% (n = 13), anterior left chest in 19% (n = 17), mid-to-posterior left chest in 41% (n = 37), and retrocardiac in 26% (n = 23). Increasingly abnormal stomach position was linearly associated with an increased odds of death (OR 4.8, 95% CI 2.1-10.9), extracorporeal membrane oxygenation (ECMO; OR 5.6, 95% CI 1.9-16.7), nonprimary diaphragmatic repair (OR 2.7, 95% CI 1.4-5.5), prolonged mechanical ventilation (OR 5.9, 95% CI 2.3-15.6), and prolonged respiratory support (OR 4.0, 95% CI 1.6-9.9). All fetuses with intra-abdominal stomach position survived without substantial respiratory morbidity or need for ECMO. DISCUSSION: Fetal stomach position is strongly associated with neonatal outcomes in isolated left CDH. This objective tool may allow for accurate prognostication in a variety of clinical settings. PMID- 26562542 TI - Novel nonsecosteroidal VDR ligands with phenyl-pyrrolyl pentane skeleton for cancer therapy. AB - A series of nonsecosteroidal vitamin D3 receptor (VDR) ligands with phenyl pyrrolyl pentane skeleton were synthesized for cancer therapy. In contrast to 1alpha,25-dihydroxyvitamin D3 (Calcitriol), these VDR ligands exhibited anti proliferative activity without inducing hypercalcemia. These compounds were evaluated for vitamin D3-agonistic ability and anti-proliferative activity in vitro. Among them, compounds 5k and 5i exhibited equivalent vitamin D3-agonistic activity compared with Calcitriol. Meanwhile, compound 5k displayed promising inhibiting profile against MCF-7, HepG-2 and Caco-2 with IC50 values of 0.00586 MUM, 0.176 MUM, and 1.01 MUM (Calcitriol: 5.58 MUM, 80.83 MUM and 4.46 MUM) respectively. Compound 5i inhibited proliferation of PC-3 with IC50 value of 0.00798 MUM (Calcitriol: 17.25 MUM). Additionally, neither of these compounds significantly elevated serum calcium in rats. PMID- 26562543 TI - Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease. AB - Neurodegenerative diseases are among the most challenging diseases with poorly known mechanism of cause and paucity of complete cure. Out of all the neurodegenerative diseases, Alzheimer's disease is the most devastating and loosening of thinking and judging ability disease that occurs in the old age people. Many hypotheses came forth in order to explain its causes. In this review, we have enlightened Glycogen Synthase Kinase-3 which has been considered as a concrete cause for Alzheimer's disease. Plaques and Tangles (abnormal structures) are the basic suspects in damaging and killing of nerve cells wherein Glycogen Synthase Kinase-3 has a key role in the formation of these fatal accumulations. Various Glycogen Synthase Kinase-3 inhibitors have been reported to reduce the amount of amyloid-beta as well as the tau hyperphosphorylation in both neuronal and nonneuronal cells. Additionally, Glycogen Synthase Kinase-3 inhibitors have been reported to enhance the adult hippocampal neurogenesis in vivo as well as in vitro. Keeping the chemotype of the reported Glycogen Synthase Kinase-3 inhibitors in consideration, they may be grouped into natural inhibitors, inorganic metal ions, organo-synthetic, and peptide like inhibitors. On the basis of their mode of binding to the constituent enzyme, they may also be grouped as ATP, nonATP, and allosteric binding sites competitive inhibitors. ATP competitive inhibitors were known earlier inhibitors but they lack efficient selectivity. This led to find the new ways for the enzyme inhibition. PMID- 26562544 TI - Anti-Candida activity and cytotoxicity of a large library of new N-substituted 1,3-thiazolidin-4-one derivatives. AB - On the basis of the recent findings about the biological properties of thiazolidinones and taking into account the encouraging results about the antifungal activity of some (thiazol-2-yl)hydrazines, new N-substituted heterocyclic derivatives were designed combining the thiazolidinone nucleus with the hydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moieties linked to the N1-hydrazine at C2 were synthesized and classified into three series according to the aromatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules were assayed for their anti-Candida effects in reference to the biological activity of the conventional topic (clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B). Finally, we investigated the selectivity against fungal cells by testing the compounds endowed with the best MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivatives were less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modelling approach has been performed against lanosterol 14-alpha demethylase (CYP51A1) to rationalize the activity of the tested compounds and to specify the target protein or enzyme. PMID- 26562545 TI - Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines. AB - Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a (18)F-labeled PDE10A imaging agent for positron emission tomography. The use of ortho-fluoropyridines as residues could potentially enable the introduction of (18)F through nucleophilic substitution for radiolabeling purposes. 2 Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule. The reference compounds, 1,8-dipyridinylimidazo[1,5-a]quinoxalines and 1-pyridinylimidazo[1,5-a]quinoxalines, show inhibitory potencies at best in the subnanomolar range and selectivity factors greater than 38 against other PDE's. 1,8-Dipyridinylimidazo[1,5-a]quinoxalines are more potent inhibitors than 1 pyridinylimidazo[1,5-a]quinoxalines. Using 2-fluoro-3-pyridinyl as residue provided the most potent inhibitors 16 (IC50 = 0.12 nM), 17 (IC50 = 0.048 nM) and 32 (IC50 = 0.037 nM). PMID- 26562546 TI - Comparative study of structural models of Leishmania donovani and human GDP mannose pyrophosphorylases. AB - Leishmania is the parasite responsible for the neglected disease leishmaniasis. Its virulence and survival require biosynthesis of glycoconjugates, whose guanosine diphospho-d-mannose pyrophosphorylase (GDP-MP) is a key player. However, experimentally resolved structures of this enzyme are still lacking. We herein propose structural models of the GDP-MP from human and Leishmania donovani. Based on a multiple sequences alignment, the models were built with MODELLER and then carefully refined with all atom molecular dynamics simulations in explicit solvent. Their quality was evaluated against several standard criteria, including their ability to bind GDP-mannose assessed by redocking calculations. Special attention was given in this study to interactions of the catalytic site residues with the enzyme substrate and competitive inhibitors, opening the perspective of medicinal chemistry developments. PMID- 26562548 TI - Controlled synthesis of N,N,N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability. AB - In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (delta=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces. PMID- 26562547 TI - The role of glycerol and water in flexible silk sericin film. AB - Silk sericin (SS) can be obtained as a byproduct during the silk fiber process, but its application has been limited due to the brittleness of the SS film. To enhance the flexibility of the SS film, glycerol (Glc) has been added as a plasticizer. The addition of Glc enhanced the elongation property of the SS film when the Glc content was 50-70 wt% of SS. Glc also induced the structural transition of SS from a random coil structure to a beta-sheet structure. The inconsistent increase of elongation and beta-sheet structure of the SS/Glc film were explained by the content of moisture in the SS/Glc film. The moisture content of the SS/Glc film increased proportionally when the Glc content was higher than 50 wt% of SS, which was the same Glc content range that exhibited the plasticizing effect. Therefore, the plasticizing effect on the SS film may occur not only because of Glc but also because of water. Furthermore, water also contributed to the increase in the beta-sheet structure development. Our results suggest that the moisture content in the plasticized protein film may play an important role when the plasticizer has hygroscopic properties. PMID- 26562549 TI - Polygonatum odoratum lectin induces apoptosis and autophagy by regulation of microRNA-1290 and microRNA-15a-3p in human lung adenocarcinoma A549 cells. AB - Polygonatum odoratum lectin (POL), a mannose-binding specific Galanthus nivalis agglutinin (GNA)-related lectin has been reported with remarkable anti proliferative and apoptosis-inducing effects against several tumor cells. Our previous research revealed that POL can induce apoptosis and autophagy in A549 cells. However, whether microRNAs (miRNAs) are involved in POL-induced apoptosis and autophagy in A549 cells has not been investigated. The aim of this study was to evaluate whether miRNAs were involved in POL-induced apoptosis and autophagy in A549 cells. In the present study, we performed microarray analysis on A549 cells to identify altered miRNAs after POL treatment. We found that miR-1290 was down-regulated after POL treatment and down-regulated miR-1290 amplifies POL induced apoptosis in A549 cells. Moreover, we revealed that glycogen synthase kinase-3beta (GSK3beta) was a direct target of miR-1290 and POL treatment could result in Wnt pathway down regulation. We also found that miR-15a-3p was up regulated after POL treatment and over-expression of miR-15a-3p resulted in A549 cells apoptosis and autophagy. In addition, we confirmed that a miR-15a-3p mediated ROS-p53 pathway was involved in POL-induced apoptosis and autophagy in A549 cells. Taken together, these data provide evidence that POL induces A549 cells apoptosis and autophagy by regulation of miR-1290 and miR-15a-3p. PMID- 26562550 TI - Crystallinity, thermal and pasting properties of starches from different potato cultivars grown in Brazil. AB - Starches from different potato cultivars were characterized as amylose and phosphorus content, crystallinity, thermal and paste properties. Statistical analysis of amylose content showed difference between starches samples and the cultivars Asterix and BRS Clara showed higher contents than others. Phosphorus content ranged from 633 to 966.7 mg kg(-1). The X-ray diffraction analysis showed that the crystallization of potato starches can be classified as B-type X-ray pattern, presenting crystallinity index ranging from 20.02% to 21.59%. Regarding thermal properties, the onset temperature did not show statistical difference between starch samples, in gelatinization and retrogradation analysis. As expected there was a significant decrease in peak temperature and enthalpy after the retrogradation of starches. For the pasting properties results showed significant difference in all cultivars. Pearson correlation coefficients showed that amylose content was negatively correlated to the onset, peak and final temperature of gelatinization, final temperature of retrogradation and pasting temperature. Phosphorus content was positively correlated to crystallinity index, peak viscosity and breakdown. Starches extracted from potato varieties showed different characteristics which can be useful to food and related industries that make use of potato starch, allowing wide options of use in various sectors of industrial application in Brazil. PMID- 26562551 TI - Synthesis, characterization and antibacterial studies of ruthenium(III) complexes derived from chitosan schiff base. AB - Chitosan can be modified chemically by condensation reaction of deacetylated chitosan with aldehyde in homogeneous phase. This condensation is carried by primary amine (NH2) with aldehyde (CHO) to form corresponding schiff base. The chitosan biopolymer schiff base derivatives are synthesized with substituted aldehydes namely 4-hydroxy-3-methoxy benzaldehyde, 2-hydroxy benzaldehyde, and 2 hydroxy-3-methoxy benzaldehyde, becomes a complexing agent or ligand. The Ruthenium(III) complexes were obtained by complexation of Ruthenium with schiff base ligands and this product exhibits as an excellent solubility and more biocompatibility. The novel series of schiff base Ruthenium(III) complexes are characterized by Elemental analysis, FT-IR spectroscopy, and Thermo-gravimetric analysis (TGA). The synthesized complexes have been subjected to antibacterial study. The antibacterial results indicated that the antibacterial activity of the complexes were more effective against Gram positive and Gram negative pathogenic bacteria. These findings are giving suitable support for developing new antibacterial agent and expand our scope for applications. PMID- 26562552 TI - Healing of skin wounds with a chitosan-gelatin sponge loaded with tannins and platelet-rich plasma. AB - A chitosan-gelatin sponge (CSGT) was prepared using a chitosan/ascorbic acid solution blend containing gelatin, followed by crosslinking with tannin acid and freeze-drying, thereby combining the chitosan sponge and gelatin sponge. The structure of the CSGT was observed by scanning electron microscopy and was shown to have uniform and abundant pores measuring about 145-240MUm in size. We also characterized the sponges by infrared spectroscopy, thermogravimetric analysis, mechanical property tests, swelling behavior analysis, water retention capacity tests, antibacterial property analysis, and cytotoxicity tests. Our data showed that the CSGT had good thermostability and mechanical properties as well as efficient water absorption and retention capacities. Moreover, the CSGT could effectively inhibit the growth of Escherichia coli and Staphylococcus aureus with low toxicity. In animal experiments, macroscopic observations and histological examinations showed that the wound covered by the CSGT healed quickly. Additionally, loading of the CSGT with platelet-rich plasma resulted in further acceleration of wound healing. Therefore, the CSGT and the CSGT with platelet rich plasma were suitable for application as a wound dressing and may have potential for use in various biomedical applications. PMID- 26562553 TI - Extraction, purification and elicitor activities of polysaccharides from Chrysanthemum indicum. AB - Polysaccharides isolated from Chrysanthemum indicum were studied for their pathogen-derived resistance against Sclerotium rolfsii sacc in Atractylodis maceocephalae koidz. The total sugar content and monosaccharide analysis were determined by phenol-sulfuric acid method and gas chromatography, and infrared spectroscopy performed for simple structure information. The activities of CAT and POD as protective enzymes in A. maceocephalae leaves were evaluated. The purified polysaccharides exhibited strong CAT and POD activities in inoculated with S. rolfsii in A. macrocephala leaves, attained the maximum value 568.3 Ug( 1)min(-1) and 604.4 Ug(-1)min(-1)respectively. Whereas, when compared with the control plants, 20mg/ml purified polysaccharides exhibited the strongest CAT and POD activities. Notably, the treatments of A. macepcephalae seedlings with C. indicum polysaccharides (CIP) decreased disease index development caused by S. rolfsii. The disease index after 10 days was significantly reduced when the seedlings treated with 20mg/ml CIP, 4.41 compared to the control plants 32.00. Given together, these results indicated that purified polysaccharides derived from C. indicum may be useful as a natural inducer. PMID- 26562554 TI - Micelle induced dissociation of DNA-ligand complexes: The effect of ligand binding specificity. AB - We investigate the SDS micelle induced dissociation of a small fluorescent ligand 4',6-diamidino-2-phenylindole (DAPI) bound to DNAs of varying sequences. Steady state and time resolved fluorescence measurements affirm minor groove binding of DAPI to poly(dA).poly(dT) and calf thymus DNA while it intercalates in poly(dG).poly(dC). Calorimetric measurements identify the former mode to be entropy driven and the intercalation to be enthalpy driven. Addition of SDS micelles extracts the ligand out of the DNA and relocates it into the micelle independent of the DNA-ligand binding mode. This process is found to be endothermic which is compensated by a huge gain in the entropy. Circular dichroism measurements indicate that the micelles do not affect the structure of DNAs, however, binding and un-binding of DAPI can introduce noticeable alteration in the DNA structure and consequently on the associated hydration which is reflected in solvation measurement. Consideration of a simple two step equilibrium model seems inadequate to account for the observed thermodynamic costs in the dissociation process. The results have been discussed on the basis of an intricate enthalpy-entropy balance. PMID- 26562555 TI - Polymeric hollow spheres assembled from ALG-g-PNIPAM and beta-cyclodextrin for controlled drug release. AB - In this paper, thermo-sensitive polymeric hollow spheres assembled from sodium alginate-graft-poly(N-isopropylacrylamide) (ALG-g-PNIPAM) and beta-cyclodextrin (beta-CD) were prepared for controlled release of 5-fluorouracil (5-FU). In aqueous solutions, beta-CD and PNIPAM formed rod-like segments through inclusion complexation interactions and sodium alginate acted as coil segments, which resulted in the formation of hollow structures. The size and wall thickness of assemblies increased with the increase of beta-CD in mixtures. The lower critical solution temperature (LCST) of hollow spheres varied in the range of 35-37 degrees C. The hollow spheres exhibited high drug loading efficiency for 5-FU due to the hydrophilic cavities. The initial composition of mixtures, temperature and pH had a significant effect on the inclusion ability and drug release. Increasing temperatures above the LCST or decreasing pH to acidic conditions, a more rapid release rate was observed. PMID- 26562556 TI - beta-Glucan as an encapsulating agent: Effect on probiotic survival in simulated gastrointestinal tract. AB - Three strains of probiotics Lactobacillus casei, Lactobacillus brevis, and Lactobacillus plantarum were encapsulated in beta-glucan matrix using emulsion technique. Further the encapsulated cells were studied for their tolerance in simulated gastrointestinal conditions and its storage stability. The average encapsulation efficiency of beta-glucan-probiotic beads was found to be 74.01%. The surface morphology of beta-glucan containing bacteria was studied using SEM. The noteworthy absorptions in the FT-IR spectra between 1300-900 cm(-1) and 2918 2925 cm(-1) corresponds to the presence of bacteria into the glucan matrix. Also, the thermal stability of beta-glucan was evaluated using Differential Scanning Calorimeter. The efficiency of beta-glucan in protecting the surviability of probiotic cells under simulated gastrointestinal conditions was studied. Results revealed significant (p<0.05) improvement to tolerance when the encapsulated cells were subjected to stresses like low pH, heat treatment, simulated intestinal conditions and storage. PMID- 26562557 TI - Feasibility study of the natural derived chitosan dialdehyde for chemical modification of collagen. AB - The aim of this study is to evaluate the chemical crosslinking effects of the natural derived chitosan dialdehyde (OCS) on collagen. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and circular dichroism (CD) measurements suggest that introducing OCS might not destroy the natural triple helix conformation of collagen but enhance the thermal-stability of collagen. Meanwhile, a denser fibrous network of cross-linked collagen is observed by atomic force microscopy. Further, scanning electron microscopy (SEM) and aggregation kinetics analysis confirm that the fibrillation process of collagen advances successfully and OCS could lengthen the completion time of collagen fibrillogenesis but raise the reconstitution rate of collagen fibrils or microfibrils. Besides, the cytocompatibility analysis implies that when the dosage of OCS is less than 15%, introducing OCS into collagen might be favorable for the cell's adhesion, growth and proliferation. Taken as a whole, the present study demonstrates that OCS might be an ideal crosslinker for the chemical fixation of collagen. PMID- 26562558 TI - Trends in Incidence of Neuroendocrine Neoplasms in Norway: A Report of 16,075 Cases from 1993 through 2010. AB - BACKGROUND: Epidemiological studies show an increasing trend in the incidence of neuroendocrine neoplasms (NENs). A significant number of NENs occur in less common primary sites, but they are often excluded from the population-based studies. We studied the incidence trends of all NENs in Norway according to different primary sites. MATERIALS AND METHODS: Our analyses were based on cancer cases diagnosed between 1993 and 2010 and reported to the national population based Cancer Registry of Norway. A total of 65 morphological codes were identified as neuroendocrine and stratified into 3 different groups of aggressiveness: low, intermediate and high. RESULTS: We identified 16,075 NENs of which 49.5% were in women. The median age at diagnosis was 65 years. The most common primary sites were the lung (48.1%) and the gastroenteropancreatic system (18.0%). Stage at diagnosis was local in 40.4% of the cases, regional in 17.5% and distant in 42.1%. The stage distribution was stable throughout the study period. The age-standardized (European) incidence rate (per 100,000 person-years) increased from 13.3 in 1993 to 21.3 in 2010 with an estimated annual increase of 5.1% in women and 2.1% in men. The increase was most pronounced for tumors of intermediate aggressiveness from 3.3 in 1993 to 7.3 in 2010. The largest annual increases were estimated for the adrenal gland (8.8%), the pancreas (6.9%) and the lungs (6.1%). CONCLUSION: The incidence of NENs increased. Most primary tumors were found in the lungs or in the gastroenteropancreatic system. The increase in the incidence differed according to the primary site, gender and tumor aggressiveness. PMID- 26562559 TI - A single amino acid substitution in movement protein of tomato torrado virus influences ToTV infectivity in Solanum lycopersicum. AB - Tomato torrado virus (ToTV), which is a tomato-infecting member of the genus Torradovirus, induces severe systemic necrosis in Solanum lycopersicum cv. Beta Lux as well as leaf malformation and chlorosis in Nicotiana benthamiana. To date, neither the tomato gene conferring resistance to the pathogen nor the ToTV encoded necrosis determinant have been characterized. We herein revealed that the phenylalanine 210 residue in the movement protein domain encoded by ToTV RNA2 is a necrosis-inducing pathogenicity determinant during tomato infection. Using a ToTV infectious RNA2 clone, we performed site-directed mutagenesis of the phenylalanine 210 residue, confirming its importance during ToTV infection and symptom manifestation in S. lycopersicum cv. Beta Lux, but not in N. benthamiana. PMID- 26562561 TI - Diagnostic and Therapeutic Challenges. PMID- 26562560 TI - Annual and diurnal variations of gaseous and particulate pollutants in 31 provincial capital cities based on in situ air quality monitoring data from China National Environmental Monitoring Center. AB - Long-term air quality data with high temporal and spatial resolutions are needed to understand some important processes affecting the air quality and corresponding environmental and health effects. The annual and diurnal variations of each criteria pollutant including PM2.5 and PM10 (particulate matter with aerodynamic diameter less than 2.5 MUm and 10 MUm, respectively), CO (carbon monoxide), NO2 (nitrogen dioxide), SO2 (sulfur dioxide) and O3 (ozone) in 31 provincial capital cities between April 2014 and March 2015 were investigated by cluster analysis to evaluate current air pollution situations in China, and the cities were classified as severely, moderately, and slightly polluted cities according to the variations. The concentrations of air pollutants in winter months were significantly higher than those in other months with the exception of O3, and the cities with the highest CO and SO2 concentrations were located in northern China. The annual variation of PM2.5 concentrations in northern cities was bimodal with comparable peaks in October 2014 and January 2015, while that in southern China was unobvious with slightly high PM2.5 concentrations in winter months. The concentrations of particulate matter and trace gases from primary emissions (SO2 and CO) and NO2 were low in the afternoon (~16:00), while diurnal variation of O3 concentrations was opposite to that of other pollutants with the highest values in the afternoon. The most polluted cities were mainly located in North China Plain, while slightly polluted cities mostly focus on southern China and the cities with high altitude such as Lasa. This study provides a basis for the formulation of future urban air pollution control measures in China. PMID- 26562562 TI - LONG-TERM RESULTS OF COMBINED AB INTERNO TRABECULOTOMY (TRABECTOME) AND SMALL GAUGE PARS PLANA VITRECTOMY. AB - PURPOSE: To report outcomes of patients who have undergone combined Trabectome and pars plana vitrectomy. METHODS: Institutional Review Board-approved retrospective chart review of patients seen at the Cincinnati Eye Institute before January 2014 undergoing combined Trabectome and pars plana vitrectomy for uncontrolled glaucoma and visually significant retina pathology. Charts were reviewed to identify changes in intraocular pressure, visual acuity, and change in glaucoma medication requirement up to 1 year after surgery. RESULTS: Four patients met the inclusion criteria with 12-month follow-up, and two of the patients were male. All patients underwent 25-gauge pars plana vitrectomy and Trabectome surgery. Mean preoperative LogMAR visual acuity was 0.39 (20/49) and 12-month LogMAR visual acuity was 0.21 (20/32) (P = 0.06). Mean preoperative intraocular pressure was 17 mmHg and mean preoperative glaucoma medication requirement was 2.5 topical medications. Twelve-month mean intraocular pressure was 12.8 mmHg (P = 0.07), and mean topical glaucoma medication requirement was 2.3 medications (P = 0.39). All patients were off steroids and anti inflammatories at the final visit. One patient developed a hyphema requiring anterior chamber washout at 1 week. No other complications occurred. CONCLUSION: The results suggest that combined Trabectome and pars plana vitrectomy seems effective in the management of glaucoma in patients with visually significant retina pathology. PMID- 26562563 TI - REAL-TIME FULL-DEPTH VISUALIZATION OF POSTERIOR OCULAR STRUCTURES: Comparison Between Full-Depth Imaging Spectral Domain Optical Coherence Tomography and Swept Source Optical Coherence Tomography. AB - PURPOSE: To compare the real-time visualization of vitreoretino-choroidal structures using full-depth imaging (FDI) spectral domain optical coherence tomography (SD-OCT) and swept-source (SS)-OCT. METHODS: Foveal scans using both FDI SD-OCT (Heidelberg Spectralis) and SS-OCT (Topcon Deep Range Imaging-OCT-1) were obtained in 40 normal eyes, 40 eyes with macular pathologies, and 40 eyes with glaucoma. Full-depth imaging SD-OCT images were obtained by manually enhancing the vitreoretinal interface first and then the choroid while averaging each OCT B-scan 100 times. Swept-source-OCT images were obtained by averaging each B-scan 96 times. After masking and randomly mixing the original OCT images, two independent physicians graded visualization of the premacular bursa, interdigitation zone line, and chorioscleral boundary, and also sharpness of choroidal structures. RESULTS: A real-time full-depth image of vitreoretino choroidal structures was successfully achieved with FDI SD-OCT in 118 cases (98.3%) and with SS-OCT in 45 cases (37.5%, P < 0.001). Full-depth imaging SD-OCT imaging was superior to SS-OCT imaging in visualizing the anterior border of the premacular bursa in 109 eyes (90.8%), with average grading of 1.63 +/- 0.53 for the FDI SD-OCT and 0.39 +/- 0.52 for the SS-OCT (P < 0.001). Swept-source-OCT was similar to FDI SD-OCT in visualizing the chorioscleral boundary in 108 eyes (90.0%), with average grading of 1.81 +/- 0.39 for the SS-OCT and 1.78 +/- 0.38 for the FDI-OCT (P = 0.566). The visualization of the interdigitation zone line was identical in the 2 imaging instruments (P = 1.000). The sharpness of the choroidal structures was greater with SS-OCT than with FDI-OCT (P < 0.001). CONCLUSION: Manual double-enhancing FDI technique using SD-OCT provided a good compromise between vitreous and retinochoroidal structures visualization in real time during scanning procedure. In contrast, SS-OCT imaged well details of choroidal sublayers. Appropriate OCT technology and software should be selected according to its application in clinical settings. PMID- 26562564 TI - ENDOSCOPY-ASSISTED VITRECTOMY AND MEMBRANE DISSECTION OF ANTERIOR PROLIFERATIVE VITREORETINOPATHY FOR CHRONIC HYPOTONY AFTER PREVIOUS RETINAL DETACHMENT REPAIR. AB - PURPOSE: To review 6-month outcomes for patients with hypotony secondary to anterior proliferative vitreoretinopathy after previous retinal detachment repair who were treated with endoscopic vitrectomy and anterior membrane dissection. METHODS: Retrospective review. All individuals underwent endoscopic vitrectomy with removal of anterior proliferative vitreoretinopathy involving the ciliary body. Outcome measurements included intraocular pressure (IOP), visual acuity, and development of phthisis bulbi. RESULTS: Fifteen eyes of 15 patients had an average of 4.5 previous intraocular surgeries (range 1-8). Forty Percent of eyes had silicone oil at the time of endoscopic surgery. Six months postoperatively, 4 eyes had IOP >11 mmHg while 11 had IOP <6 mmHg. The nonresponder group was older in age, had more previous intraocular surgeries, and a lower preoperative IOP. There were no differences in visual acuity or the development of prephthisis at any point. No eyes underwent enucleation or evisceration. CONCLUSION: Endoscopy assisted vitrectomy with removal of anterior proliferative vitreoretinopathy from the ciliary body is an effective treatment for chronic hypotony after previous retinal detachment repair in a minority of cases. The IOP improved in patients who tended to be younger and who had fewer previous intraocular surgeries. Further study is indicated to evaluate long-term outcomes and predictors of surgical success. PMID- 26562565 TI - RETINAL MORPHOMETRY CHANGES MEASURED WITH SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY AFTER PAN-RETINAL PHOTOCOAGULATION IN PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY. AB - PURPOSE: To identify the effects of pan-retinal laser treatment on the integrity of neurosensory retinal layers. METHODS: Patients were examined with fluorescence angiography after a standardized examination for diabetic retinopathy and a peripapillary ring scan with spectral domain optical coherence tomography. A single-session pan-retinal photocoagulation was performed using the PASCAL pattern scanning argon laser applying a minimum of 1,500 spots. Optical coherence tomography was evaluated more than 6 months. RESULTS: Eighteen eyes of 12 consecutive patients with new onset, treatment-naive proliferative diabetic retinopathy secondary to diabetes Type 2 were treated and retinal optical coherence tomography morphology evaluated. Retinal nerve fiber layer thickness increased statistically significantly from baseline to week 1, when it reached its peak. The combined thickness of the outer plexiform and the inner nuclear layers and the combined thickness of the inner plexiform and the ganglion cell layers showed no relevant changes. The combined thickness of the retinal pigment epithelium and the photoreceptor cell layers decreased at month 1 followed by a steady increase in thickness, which remained below baseline values over time. CONCLUSION: Pan-retinal photocoagulation in proliferative diabetic retinopathy leads to a slowly reversible, marked biological response with statistically significant morphometric changes detected by spectral domain optical coherence tomography. Swelling of the retinal nerve fiber and outer nuclear layers induce an increase in peripapillary total retinal thickness. Simultaneously, the photoreceptor and retinal pigment epithelium layers decrease in thickness. These changes indicate diffuse retinal inflammation after pan-retinal laser therapy. PMID- 26562566 TI - SILICONE OIL BARRIER SUTURES IN APHAKIC EYES WITH IRIS DEFECTS. AB - PURPOSE: To evaluate the efficacy and safety of silicone oil barrier sutures in aphakic eyes with iris defects. METHODS: Sixteen aphakic and iris-defective eyes of 16 patients who underwent a pars plana vitrectomy procedure with silicone oil tamponade because of retinal detachment were included in this retrospective study. Silicone oil barrier sutures were placed as a grid pattern within the plane of the previous iris after vitrectomy and before silicone oil injection. RESULTS: The mean follow-up time after silicone oil barrier suture operations was 12.0 +/- 6.8 months. Silicone oil was present in the anterior chamber in five eyes (31%) at the last visit. These eyes also had hypotony, band keratopathy, and anterior proliferative vitreoretinopathy. CONCLUSION: In this study, silicone oil barrier sutures were proven to be safe and effective in preventing silicone oil corneal endothelium touch in aphakic eyes with iris defects, unless hypotony was present because of anterior proliferative vitreoretinopathy. PMID- 26562567 TI - Video Angiography of Cilioretinal Artery Infarction in Central Retinal Vein Occlusion. PMID- 26562568 TI - POSTOPERATIVE POSITIONING IN MACULAR HOLE SURGERY: An Objective Evaluation of Nonsupine Positioning and the Effect of the "Tennis Ball Technique". AB - PURPOSE: To objectively evaluate patients' compliance with a nonsupine positioning (NSP) regimen after macular hole surgery and to investigate whether supine positioning time during the first postoperative nights is reduced when a tennis ball is mounted onto the back of the nightshirt. METHODS: A "position monitoring device" capable of recording the time the head is kept in a supine position was attached to the patient's forehead. In a randomized, controlled, crossover study, the accumulated time each patient spent in a supine position was recorded during two consecutive postoperative nights, both when the "tennis ball technique" (TBT) was used and when it was not, respectively. RESULTS: The study included 40 participants. A mean supine time of 14 minutes and 47 seconds was registered with the NSP regimen. When applying the TBT, the mean supine time was significantly reduced to 4 minutes and 24 seconds (P = 0.01). Seven "noncompliant" participants with >30 minutes supine time without TBT had the most marked reduction in supine time from a mean of 63 minutes and 2 seconds, to 3 minutes and 46 seconds, with TBT (P = 0.02). CONCLUSION: During an NSP regimen, patients generally maintain a high level of compliance after macular hole surgery. The TBT further improves their compliance significantly. PMID- 26562570 TI - Meningococcal disease among men who have sex with men - United States, January 2012-June 2015. AB - Since 2012, three clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States. During 2012, 13 cases of meningococcal disease among MSM were reported by the New York City Department of Health and Mental Hygiene (1); over a 5-month period during 2012 2013, the Los Angeles County Department of Public Health reported four cases among MSM; and during May-June 2015, the Chicago Department of Public Health reported seven cases of meningococcal disease among MSM in the greater Chicago area. MSM have not previously been considered at increased risk for meningococcal disease. Determining outbreak thresholds* for special populations of unknown size (such as MSM) can be difficult. The New York City health department declared an outbreak based on an estimated increased risk for meningococcal infection in 2012 among MSM and human immunodeficiency virus (HIV)-infected MSM compared with city residents who were not MSM or for whom MSM status was unknown (1). The Chicago Department of Public Health also declared an outbreak based on an increase in case counts and thresholds calculated using population estimates of MSM and HIV infected MSM. Local public health response included increasing awareness among MSM, conducting contact tracing and providing chemoprophylaxis to close contacts, and offering vaccination to the population at risk (1-3). To better understand the epidemiology and burden of meningococcal disease in MSM populations in the United States and to inform recommendations, CDC analyzed data from a retrospective review of reported cases from January 2012 through June 2015. PMID- 26562569 TI - REDUCTION OF VITREOUS PROSTAGLANDIN E2 LEVELS AFTER TOPICAL ADMINISTRATION OF INDOMETHACIN 0.5%, BROMFENAC 0.09%, AND NEPAFENAC 0.1. AB - PURPOSE: To assess vitreous concentrations of nonsteroidal anti-inflammatory drugs (NSAIDs) and prostaglandin E2 (PGE2) in patients treated with NSAIDs before vitrectomy for macular pucker. METHODS: A prospective, investigator-masked, randomized study was performed in 64 patients scheduled to undergo vitrectomy. The patients were randomized 1:1:1:1 to receive indomethacin 0.5%, bromfenac 0.09%, nepafenac 0.1%, or placebo three times a day. NSAIDs and PGE2 levels were evaluated in vitreous samples collected at the beginning of surgery. RESULTS: Mean (SD) vitreous concentrations of the study drugs were 503.13 (241.1) pg/mL for indomethacin, 302.5 (91.03) pg/mL for bromfenac, and 284.38 (128.2) pg/mL for nepafenac. Mean (SD) vitreous PGE2 levels were 247.9 (140.9) pg/mL for indomethacin, 322.12 (228.1) pg/mL for bromfenac, 448.8 (261.1) pg/mL for nepafenac, and 1,133 (323.9) pg/mL for placebo. All three NSAIDs reduced vitreous PGE2 levels to a statistically significant extent, without a significant difference among them. CONCLUSION: All assessed NSAIDs penetrated the vitreous and lowered basal PGE2 levels. A greater penetration was associated with pseudophakic eyes. The important inhibition of prostaglandins in the retina may have a clinical effect on the management of inflammatory retina diseases. PMID- 26562571 TI - PET/CT Helps Downgrade an Aggressive-Appearing Rib Mass to a Probable Benign Lesion in a 9-Year-Old Girl. AB - We present a case of a 9-year-old girl with no significant medical history who developed acute onset of shortness of breath and upper chest pain during cheerleading practice. Laboratory results and physical examination were unremarkable. Chest radiograph and chest CT showed an expansile lytic aggressive appearing mass within the left sixth rib. Subsequent F-FDG PET/CT showed a left sixth rib lesion that was not hypermetabolic and appeared benign. Biopsy yielded a diagnosis of enchondroma, a benign intramedullary tumor that accounts for 24% of all bone tumors in children as well as adolescents. PMID- 26562572 TI - Do the Symptoms of Kleine-Levin Syndrome Correlate With the Hypometabolism of the Thalamus on FDG PET? AB - A 15-year-old adolescent boy had experienced intermittent, recurrent hypersomnia lasting for 1 week to 3 weeks for more than 3 years. He was diagnosed with Kleine Levin Syndrome clinically. The brain MRI, video EEG, and serum and cerebrospinal fluid analysis did not show any abnormality. An FDG PET/CT scanning was acquired when the patient was symptomatic, showing marked symmetric hypometabolism in the thalamus and hypothalamus in the symptomatic phase, as well as mild homogeneous decreased glucose metabolism in the cortex. Interestingly, another FDG PET/CT scan acquired when the patient was asymptomatic found much less severe hypometabolism in the thalamus and hypothalamus. PMID- 26562573 TI - 18F-FDG PET/CT Demonstrated the Multiple Myeloma From Prostate. AB - Prostatic plasmacytoma is an exceptionally rare type of multiple myeloma. The present study reports a patient with multiple myeloma arising from the prostate, with normal serum and urine monoclonal protein. The final diagnosis of multiple myeloma from prostate was based on pathologic and immunohistochemical findings. PMID- 26562574 TI - A Case of a Man With Isolated Breast Metastasis From Lung Adenocarcinoma Incidentally Detected by FDG PET/CT. AB - Breast metastases from an extramammary primary tumor are very rare, particularly in men. In this study, we present a case of a 74-year-old man with isolated breast metastasis from lung adenocarcinoma as an incidental finding on PET/CT and diagnosed concomitantly with the primary tumor. Detection of isolated incidental metastatic lesions in the breast on PET/CT imaging has a significant clinical impact on patients with known malignant disease due to change of disease stage, management, and also treatment method. PMID- 26562575 TI - 18F-FDG PET/CT Imaging of Bilateral Renal Metastasis of Breast Adenoid Cystic Carcinoma. AB - We report the case of a 65-year-old woman with a history of adenoid cystic carcinoma (ACC) of the breast. Fifteen years after mastectomy, the patient underwent a right upper lobectomy for a lung mass, and biopsy indicated ACC metastasis. Ten years after lobectomy, an F-FDG PET/CT was performed for restaging to rule out further metastases. We observed intense FDG uptake in enlarged polylobulated kidneys, which was biopsy proven as ACC metastasis. PMID- 26562576 TI - Increased 99mTc-MDP Activity in a Partially Calcified Malignant Mediastinal Teratoma. AB - A 41-year-old woman presented with cough and shortness of breath for 3 weeks. Chest x-ray and CT showed a large, partially calcified soft tissue mass adjacent to the right side of the heart. Whole-body bone was acquired to evaluate possible metastases, which showed abnormal accumulation of Tc-MDP in the right chest. Further SPECT/CT imaging that demonstrated intense Tc-MDP activity was mainly in the calcification portion of mass. Histopathological examination from biopsy specimen of the lesion was consistent with malignant teratoma. PMID- 26562577 TI - Isolated Calcaneal Metastasis: An Unusual Presentation of Lung Carcinoma as Heel Pain. AB - A 63-year-old woman initially presented with progressive left foot pain for 3 months, not responding to conservative management. MRI of the left foot showed a suspicious lesion in calcaneus. An open biopsy was consistent with metastatic lung adenocarcinoma. Tc-MDP total-body bone scintigraphy was ordered for possible other bony lesions, and only left calcaneus lesion was identified on bone scan. CT scan of the chest revealed a soft tissue mass in the superior aspect of the right lower lobe. Staging FDG PET/CT showed hypermetabolic right lung mass and left calcaneus lesion. She received chemotherapy and local radiation to the left calcaneus metastatic lesion. PMID- 26562578 TI - FDG PET/CT Appearance of Radiation Nephritis. AB - It is often challenging to assess renal activity on FDG-PET/CT due to intense physiological activity in the collecting system, thus any unusual intrarenal activity should be evaluated carefully. While increased bone tracer uptake in the irradiated region of the kidneys has been reported in the literature, altered biodistribution of FDG in irradiated renal tissue is not well described. We report a case of FDG PET/CT showing increased FDG activity in small portions of the kidneys that were previously irradiated. PMID- 26562579 TI - Metastatic Insulinoma Pancreatic Neuroendocrine Tumor Treated With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy: A Suggested Protocol. AB - A 70-year-old woman presented with frequent episodes of hypoglycemia. Imaging revealed a 6-cm pancreatic mass with several liver lesions. The pancreatic mass was resected and confirmed to be a well-differentiated insulinoma. Surgery improved but did not resolve her hypoglycemic episodes, and she was referred for peptide receptor radionuclide therapy with 177Lu-DOTATATE to treat her residual disease. A modified protocol with a continuous IV dextrose infusion was used, and the treatments were well tolerated. After 4 induction and 2 maintenance treatments, her hypoglycemic symptoms resolved completely and her disease stabilized. She has been progression free for 24 months. PMID- 26562580 TI - Schmorl Nodes Can Cause Increased 68Ga DOTATATE Activity on PET/CT, Mimicking Metastasis in Patients With Neuroendocrine Malignancy. AB - Schmorl node (SN) is the herniation of the nucleus pulposus through the cartilaginous and bony endplate into the adjacent vertebral body. It is documented that SNs produce areas of moderately increased F-FDG uptake. We present a case of a patient with history of neuroendocrine tumor, who underwent Ga DOTATATE PET/CT for follow-up, showing increased focal vertebral uptake suggestive of bone metastasis. CT revealed typical findings of an SN. The presented case indicates that SNs should be considered when encountering focally increased skeletal uptake in Ga DOTATATE PET/CT studies, which can mimic metastasis in patients with history of neuroendocrine tumors. PMID- 26562581 TI - High Incidence of Undiagnosed Cervical Myelopathy in Patients With Hip Fracture Compared With Controls. AB - OBJECTIVES: To identify the incidence of undiagnosed cervical myelopathy in patients who fall and develop hip fractures compared with age-matched controls. DESIGN: Prospective, case-control study. SETTING: University level 1 Trauma Center. PATIENTS/PARTICIPANTS: Consecutive patients who presented with hip fractures after a fall. A total of 159 patients were screened; 66 patients (38 arthroplasty, 28 fracture) were eligible for enrollment in the study. Exclusion criteria included cognitive impairment, known diagnosis of cervical myelopathy, previous cervical spine surgery, inability to comply with examination, or refusal to participate. The control group was age-matched elderly patients who underwent total hip arthroplasty (THA). INTERVENTION: Patient interview and physical examination for cervical myelopathy. MAIN OUTCOME MEASUREMENTS: Myelopathy was diagnosed by clinical history elements (Japanese Orthopaedic Association score <=15) and pathologic reflexes. Comparison of the incidence of myelopathy in the study population with the control population was performed using Fisher exact test. RESULTS: There were no statistically significant differences between the fracture and THA groups in mean patient age or male/female ratio. There was a statistically significant increased incidence of myelopathy in hip fracture patients (18%) compared with the THA group (0%, P = 0.01). CONCLUSIONS: Hip fracture is a complex multifactorial process, and most patients (60%) were excluded due to known cognitive impairment. However, 18% of previously undiagnosed patients who were cognitively intact manifested clinical findings consistent with cervical spondylotic myelopathy. Consideration should be given to screening for undiagnosed myelopathy among patients with hip fracture to reduce the risk of subsequent fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26562582 TI - Toward a More Robust Prediction of Pulmonary Embolism in Trauma Patients: A Risk Assessment Model Based on 38,000 Patients. AB - OBJECTIVES: Pulmonary embolism (PE) is a rare but sometimes fatal complication of trauma. Risk stratification models identify patients at increased risk of PE; however, they are often complex and difficult to use. This research aims to develop a model, based on a large sample of trauma patients, which can be easily and quickly used at the time of admission to predict PE. METHODS: This study used trauma registry data from 38,597 trauma patients. Of these, 239 (0.619%) developed a PE. We targeted demographic and injury data, prehospital information, and data on treatments and events during hospitalization. A multivariate binary logistic regression model was developed to predict the odds of developing a PE during hospitalization. The model was developed using a 50% randomly selected development subsample and then tested for accuracy using the remaining 50% validation sample. RESULTS: We found 7 statistically significant predictors of PE, including (1) age [odds ratio (OR) = 1.01; 95% CI, 1.00-1.02; P = 0.05], (2) obesity (OR = 2.54; 95% CI, 1.29-4.99; P < 0.01), (3) injury from motorcycle accident (OR = 2.01; 95% CI, 1.25-3.22; P < 0.01), (4) arrival by helicopter (OR = 2.91; 95% CI, 1.16-7.27; P = 0.02), (5) emergency department admission pulse rate (OR = 1.01; 95% CI, 1.0-1.02; P = 0.06), (6) admission to intensive care unit (OR = 5.03; 95% CI, 3.12-8.12; P < 0.01), and (7) injury location, including thorax (OR = 1.57; 95% CI, 1.04-2.37; P = 0.03), abdomen (OR = 1.56; 95% CI, 1.04 2.33; P = 0.03), and lower extremity injuries (OR = 2.85; 95% CI, 3.12-8.12; P < 0.01). Our model was able to discriminate between predicted and actual PE events with a receiver operating characteristic area under the curve of 0.87. By identifying the top 25% high-risk patients, we were able to predict 80%-84% of pulmonary emboli. CONCLUSIONS: This knowledge allows us to focus stronger thromboprophylactic efforts on patients at highest risk. This model can be used to rapidly identify trauma patients at high risk for PE. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26562583 TI - A Comparison of Exposure Between the Classic and Modified Judet Approaches to the Scapula. AB - OBJECTIVES: A debate exists over the optimal approach for addressing fractures of the scapula and glenoid. The purpose of this study is to (1) quantify and compare osseous exposure using modified Judet (MJ) and classic Judet (CJ) approaches and (2) assess the change in scapular exposure after triceps release from the inferior glenoid. METHODS: Ten arms on 5 fresh-frozen torsos underwent MJ and CJ approaches. A triceps release was performed following the CJ approach in all specimens. Visual and/or palpable access to relevant surgical landmarks was recorded. Calibrated digital photographs were taken of each approach and analyzed using Image J (NIH, Bethesda, MD) to calculate the surface area of exposed bone. RESULTS: The MJ and CJ approaches exposed 16.8 (+/-7.58) cm(2) and 98.6 (+/ 25.39) cm(2) of bone, respectively (P < 0.001). The full medial and lateral borders of the scapula were visualized in all approaches with mobilization of the teres minor. Palpable access to the full scapular spine was possible in all cadavers. Although the MJ and CJ approaches only allowed the inferior gleniod neck to be visualized in 1 and 2 specimens, respectively, performing a triceps release provided access to this structure. It also increased the CJ exposure by 12.6 cm(2) (P < 0.001) and allowed palpation of the anterior glenoid margin in 100% of specimens. CONCLUSIONS: In conclusion, the MJ approach allows similar access to landmarks important for reduction and fixation while exposing only 20% of the surface area typically visualized with the CJ approach. PMID- 26562585 TI - Structure-Specific Liquid Crystal Anchoring Induced by the Molecular Combing of Short Oligonucleotides. AB - Surface-immobilized oligonucleotides were "combed" by meniscus motion and exposed to a nematic liquid crystal (LC). Although the oligonucleotides were as short as 16 bases, they were apparently oriented by this process and, in turn, successfully biased the orientation of the adjacent LC material. Single-stranded DNA (ssDNA) induced LC orientation in the combing direction, while hybridized double-stranded DNA (dsDNA) rotated the azimuthal LC orientation by ~30 degrees from the combing direction. The sensitivity of the chiral response to mixed ssDNA/dsDNA surfaces was characterized by employing complementary DNA that was longer than the immobilized DNA, resulting in single-stranded overhangs of various lengths. A rotated LC orientation was observed even when more than 70% of the DNA was single-stranded, and the transition from the rotated to nonrotated response was apparently discontinuous as a function of ssDNA surface coverage. These phenomena represent a sensitive DNA hybridization detection strategy that can potentially comprise a multiplexed assay. PMID- 26562586 TI - Spontaneous Partitioning of Californium from Curium: Curious Cases from the Crystallization of Curium Coordination Complexes. AB - The reaction of (248)CmCl3 with excess 2,6-pyridinedicarboxylic acid (DPA) under mild solvothermal conditions results in crystallization of the tris-chelate complex Cm(HDPA)3 . H2O. Approximately half of the curium remains in solution at the end of this process, and evaporation of the mother liquor results in crystallization of the bis-chelate complex [Cm(HDPA)(H2DPA)(H2O)2Cl]Cl.2H2O. (248)Cm is the daughter of the alpha decay of (252)Cf and is extracted in high purity from this parent. However, trace amounts of (249,250,251)Cf are still present in all samples of (248)Cm. During the crystallization of Cm(HDPA)3 . H2O and [Cm(HDPA)(H2DPA)(H2O)2Cl]Cl . 2H2O, californium(III) spontaneously separates itself from the curium complexes and is found doped within crystals of DPA in the form of Cf(HDPA)3. These results add to the growing body of evidence that the chemistry of californium is fundamentally different from that of earlier actinides. PMID- 26562588 TI - Co-occurrence of Photochemical and Microbiological Transformation Processes in Open-Water Unit Process Wetlands. AB - The fate of anthropogenic trace organic contaminants in surface waters can be complex due to the occurrence of multiple parallel and consecutive transformation processes. In this study, the removal of five antiviral drugs (abacavir, acyclovir, emtricitabine, lamivudine and zidovudine) via both bio- and phototransformation processes, was investigated in laboratory microcosm experiments simulating an open-water unit process wetland receiving municipal wastewater effluent. Phototransformation was the main removal mechanism for abacavir, zidovudine, and emtricitabine, with half-lives (t1/2,photo) in wetland water of 1.6, 7.6, and 25 h, respectively. In contrast, removal of acyclovir and lamivudine was mainly attributable to slower microbial processes (t1/2,bio = 74 and 120 h, respectively). Identification of transformation products revealed that bio- and phototransformation reactions took place at different moieties. For abacavir and zidovudine, rapid transformation was attributable to high reactivity of the cyclopropylamine and azido moieties, respectively. Despite substantial differences in kinetics of different antiviral drugs, biotransformation reactions mainly involved oxidation of hydroxyl groups to the corresponding carboxylic acids. Phototransformation rates of parent antiviral drugs and their biotransformation products were similar, indicating that prior exposure to microorganisms (e.g., in a wastewater treatment plant or a vegetated wetland) would not affect the rate of transformation of the part of the molecule susceptible to phototransformation. However, phototransformation strongly affected the rates of biotransformation of the hydroxyl groups, which in some cases resulted in greater persistence of phototransformation products. PMID- 26562587 TI - Comparative Molecular Dynamics Studies of Human DNA Polymerase eta. AB - High-energy ultraviolet radiation damages DNA through the formation of cyclobutane pyrimidine dimers, which stall replication. When the lesion is a thymine-thymine dimer (TTD), human DNA polymerase eta (Pol eta) assists in resuming the replication process by inserting nucleotides opposite the damaged site. We performed extensive molecular dynamics (MD) simulations to investigate the structural and dynamical effects of four different Pol eta complexes with or without a TTD and with either dATP or dGTP as the incoming base. No major differences in the overall structures and equilibrium dynamics were detected among the four systems, suggesting that the specificity of this enzyme is due predominantly to differences in local interactions in the binding regions. Analysis of the hydrogen-bonding interactions between the enzyme and the DNA and dNTP provided molecular-level insights. Specifically, the TTD was observed to engage in more hydrogen-bonding interactions with the enzyme than its undamaged counterpart of two normal thymines. The resulting greater rigidity and specific orientation of the TTD are consistent with the experimental observation of higher processivity and overall efficiency at TTD sites than at analogous sites with two normal thymines. The similarities between the systems containing dATP and dGTP are consistent with the experimental observation of relatively low fidelity with respect to the incoming base. Moreover, Q38 and R61, two strictly conserved amino acids across the Pol eta family, were found to exhibit persistent hydrogen bonding interactions with the TTD and cation-pi interactions with the free base, respectively. Thus, these simulations provide molecular level insights into the basis for the selectivity and efficiency of this enzyme, as well as the roles of the two most strictly conserved residues. PMID- 26562589 TI - Sustainable Rejuvenation of Electrochromic WO3 Films. AB - Devices relying on ion transport normally suffer from a decline of their long term performance due to irreversible ion accumulation in the host material, and this effect may severely curtail the operational lifetime of the device. In this work, we demonstrate that degraded electrochromic WO3 films can sustainably regain their initial performance through galvanostatic detrapping of Li(+) ions. The rejuvenated films displayed degradation features similar to those of the as prepared films, thus indicating that the detrapping process is effectively reversible so that long-term performance degradation can be successfully avoided. Detrapping did not occur in the absence of an electric current. PMID- 26562590 TI - Precollege Predictors of Incapacitated Rape Among Female Students in Their First Year of College. AB - OBJECTIVE: The first year of college is an important transitional period for young adults; it is also a period associated with elevated risk of incapacitated rape (IR) for female students. The goal of this study was to identify prospective risk factors associated with experiencing attempted or completed IR during the first year of college. METHOD: Using a prospective cohort design, we recruited 483 incoming first-year female students. Participants completed a baseline survey and three follow-up surveys over the next year. At baseline, we assessed precollege alcohol use, marijuana use, sexual behavior, and, for the subset of sexually experienced participants, sex-related alcohol expectancies. At the baseline and all follow-ups, we assessed sexual victimization. RESULTS: Approximately 1 in 6 women (18%) reported IR before entering college, and 15% reported IR during their first year of college. In bivariate analyses, precollege IR history, precollege heavy episodic drinking, number of precollege sexual partners, and sex-related alcohol expectancies (enhancement and disinhibition) predicted first-year IR. In multivariate analyses with the entire sample, only precollege IR (odds ratio = 4.98, p < .001) remained a significant predictor. However, among the subset of sexually experienced participants, both enhancement expectancies and precollege IR predicted IR during the study year. CONCLUSIONS: IR during the first year of college is independently associated with a history of IR and with expectancies about alcohol's enhancement of sexual experience. Alcohol expectancies are a modifiable risk factor that may be a promising target for prevention efforts. PMID- 26562591 TI - Effectiveness of Alcohol Brief Intervention in a General Hospital: A Randomized Controlled Trial. AB - OBJECTIVE: The purpose of this study was to examine the effectiveness of an alcohol brief intervention (ABI) on alcohol consumption in hazardous or harmful drinkers compared with screening alone within a general hospital setting. METHOD: Following screening, 124 hazardous or harmful drinkers (103 men, ages 18-80 years, score of 3-12 on the Fast Alcohol Screening Test [FAST]) admitted to medical and orthopedic wards during the 13-month recruitment period were randomized to receive an ABI or control. The intervention group received an ABI where they were supported to set their own personalized alcohol reduction goals, and both groups received a health information leaflet. Retrospective alcohol consumption for 7 days was reported for the week, before hospital admission and 6 months after it. RESULTS: Demographics and clinical characteristics at baseline showed no statistical differences between the two groups on all variables except FAST score, which was higher in the intervention group (p <= .05). A reduction of 85 grams of alcohol per week (95% CI [162.46, 7.54]) was observed between groups in favor of the intervention group based on changes from baseline. However, there was no significant difference between groups for absolute grams of alcohol per week at 6 months. A significant mean difference in favor of the intervention group (U = 1,537, p = .043) was observed for weekly heavy drinking episodes. CONCLUSIONS: Our results suggest screening with delivery of ABI for harmful/hazardous drinkers in a general hospital is beneficial in reducing alcohol consumption compared with screening alone. PMID- 26562592 TI - Childhood Physical and Sexual Abuse and Social Network Patterns on Social Media: Associations With Alcohol Use and Problems Among Young Adult Women. AB - OBJECTIVE: The aim of the present study was to examine the links between severities of child abuse (physical vs. sexual), and alcohol use versus problems via social media (Facebook) peer connection structures. METHOD: A total of 318 undergraduate female students at a public university in the United States reported severity of child abuse experiences and current alcohol use and problems. Social network data were obtained directly from the individuals' Facebook network. RESULTS: Severity of childhood physical abuse was positively linked to alcohol use and problems via eigenvector centrality, whereas severity of childhood sexual abuse was negatively linked to alcohol use and problems via clustering coefficient. CONCLUSIONS: Childhood physical and sexual abuse were linked positively and negatively, respectively, to online social network patterns associated with alcohol use and problems. The study suggests the potential utility of these online network patterns as risk indices and ultimately using social media as a platform for targeted preventive interventions. PMID- 26562594 TI - A Dual-Process Examination of Alcohol-Related Consequences Among First-Year College Students. AB - OBJECTIVE: Despite showing reductions in college student drinking, interventions have shown some inconsistency in their ability to successfully decrease consequences. With the goal of improving prevention efforts, the purpose of this study was to examine the role of consequence-specific constructs, in addition to drinking, that influence students' experiences with alcohol-related problems. The study examined how drinking and protective behaviors mediated the relationships between students' willingness to experience consequences, intentions to avoid them, and four categories of alcohol-related problems (physiological, social, sexual, and academic). METHOD: First-year college student drinkers (n = 2,024) at a large northeastern university completed surveys during the fall and spring of their freshman year. RESULTS: As expected, different patterns of associations emerged for physiological and nonphysiological consequences. When physiological consequences (e.g., hangover, vomiting) were examined, drinking significantly mediated the effect of willingness on the consequences. Drinking-specific protective behaviors indirectly influenced consequences through drinking behaviors whereas general protective behaviors did not. When nonphysiological (e.g., social, sexual, academic) consequences were examined, drinking and general protective behaviors emerged as significant mediators of the effects of willingness and intentions on the consequences, whereas drinking-specific protective behaviors did not. CONCLUSIONS: The results suggest that prevention efforts (e.g., personalized feedback) could be tailored to address specific types of protective behaviors as well as specific types of consequences frequently experienced by college students. PMID- 26562593 TI - The Association of Low Parental Monitoring With Early Substance Use in European American and African American Adolescent Girls. AB - OBJECTIVE: Research indicates that low parental monitoring increases the risk for early substance use. Because low parental monitoring tends to co-occur with other familial and neighborhood factors, the specificity of the association is challenging to establish. Using logistic regression and propensity score analyses, we examined associations between low parental monitoring and early substance use in European American (EA) and African American (AA) girls, controlling for risk factors associated with low parental monitoring. METHOD: Participants were 3,133 EA and 523 AA girls from the Missouri Adolescent Female Twin Study with data on parental monitoring assessed via self-report questionnaire, and with ages at first use of alcohol, tobacco, and cannabis queried in at least one of three diagnostic interviews (median ages = 15, 22, and 24 years). RESULTS: The rate of early alcohol use was greater in EA than AA girls, whereas the proportion of AA girls reporting low parental monitoring was higher than in EA girls. EA girls who experienced low parental monitoring were at elevated risk for early alcohol, tobacco, and cannabis use, findings supported in both logistic regression and propensity score analyses. Evidence regarding associations between low parental monitoring and risk for early substance use was less definitive for AA girls. CONCLUSIONS: Findings highlight the role of parental monitoring in modifying risk for early substance use in EA girls. However, we know little regarding the unique effects, if any, of low parental monitoring on the timing of first substance use in AA girls. PMID- 26562595 TI - Does the How Mediate the Why? A Multiple Replication Examination of Drinking Motives, Alcohol Protective Behavioral Strategies, and Alcohol Outcomes. AB - OBJECTIVE: The present study attempted to assess the evidence of use of protective behavioral strategies (PBS) as a mediator in the relationship between drinking motives and alcohol outcomes. Specifically, to understand various statistical approaches in modeling this proposed mediation model (e.g., drinking motives to PBS use to alcohol outcomes), we tried to replicate models based on earlier research. METHOD: To maximize the robustness of our replication attempts, we conducted each replication attempt across two distinct data sets whenever possible. Participants were recruited from psychology department research pools at a large southeastern U.S. university (Sample 1; n = 774) and a large southwestern U.S. university (Sample 2; n = 594). We matched the original articles' analytic procedures as closely as possible including overall analysis approach, measurement of variables, and inclusion/exclusion criteria. RESULTS: Consistent with previous studies, we found that PBS use may be a mechanism through which both positively reinforcing (i.e., social and enhancement) motives and coping motives relate to alcohol outcomes (e.g., alcohol-related consequences). Specifically, students who tend to drink for these specific motives appear to use fewer PBS, which may place them at risk for heavier, more problematic drinking. CONCLUSIONS: Our results suggest that when drinking motives are examined separately, they demonstrate differential relationships with PBS use and alcohol outcomes. Overall, it is clear that PBS use plays a role in the drinking motives-alcohol outcomes relationship, but this role varies by type of motive. PMID- 26562596 TI - The Prospective Joint Effects of Self-Regulation and Impulsive Processes on Early Adolescence Alcohol Use. AB - OBJECTIVE: Dual-process models propose that behavior is influenced by the interactive effect of impulsive (automatic) and self-regulatory (controlled) processes. Elaborations of this model posit that the effect of impulsive processes on alcohol use is influenced by capacity and motivation to self regulate. The interactive effect of these three processes on drinking has not previously been tested. The goal of this study was to provide a developmental extension of this model to early adolescent alcohol use and to test the three-way interaction between impulsive processes (implicit alcohol cognition), self regulatory capacity (inhibitory and activation control), and self-regulatory motivation (negative alcohol outcome expectancies [AOE]) in a 1-year prospective prediction of adolescent alcohol use. METHOD: Adolescents (N = 325; 54% girls, mean age = 13.6 years at baseline) completed the Single Category Implicit Association Test and self-reports of alcohol expectancies and use. Inhibitory and activation control were based on parental report. RESULTS: Negative AOE and inhibitory/activation control were supported as moderators of the effect of implicit alcohol cognition on 1-year prospective alcohol use. As expected, weak implicit negative alcohol cognition was associated with elevated alcohol use when both negative AOE and inhibitory control were low. Contrary to hypothesis, when activation control was high, weak implicit negative alcohol cognition was unrelated to alcohol use if negative AOE were high (p = .72) (vs. low, p <.01). Activation control may reflect the ability to plan ahead and act pro-socially. CONCLUSIONS: Our study supports current theory suggesting alcohol use is influenced by a complex interplay of impulsive and self-regulatory processes. PMID- 26562598 TI - Patterns and Correlates of Sustained Heroin Abstinence: Findings From the 11-Year Follow-Up of the Australian Treatment Outcome Study. AB - OBJECTIVE: We report on patterns and correlates of sustained abstinence at the 11 year follow-up of the Australian Treatment Outcome Study cohort. METHOD: This report is a longitudinal cohort analysis of patterns of recent and sustained abstinence. RESULTS: A total of 431 (70.1%) of the original 615 participants were interviewed, and 10.2% were deceased. The mean elapsed time since heroin initiation was 20.4 years (SD = 7.2). At the 11-year follow-up, heroin abstinence over the preceding month was reported by 75.2%. A period of at least 1 month's abstinence across the follow-up was reported by 97.7% and at least 1 year by 89.9%, whereas 52.2% reported an abstinence period of 5 or more consecutive years. Sustained abstinence across the entire follow-up period was reported by 5.6%. Independent correlates of 5 or more consecutive years of heroin abstinence were female gender (odds ratio [OR] = 1.73), not being currently enrolled in a drug treatment program (OR = 2.16), and fewer treatment episodes across the follow-up (OR = 0.90, 95% CI [0.85, 0.96]). CONCLUSIONS: The clinical profile of the cohort at the 11-year follow-up was encouraging, with the majority currently heroin abstinent, a proportion that has increased across time. Although only a small minority maintained abstinence over the entire period, half had sustained abstinence for at least 5 consecutive years. With the exception of gender, baseline characteristics made poor predictors of long-term abstinence. Treatment stability, however, appears crucial in maintaining abstinence. PMID- 26562597 TI - The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use. AB - OBJECTIVE: During adolescence, neurobiological maturation occurs concurrently with social and interpersonal changes, including the initiation of alcohol and other substance use. The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is designed to disentangle the complex relationships between onset, escalation, and desistance of alcohol use and changes in neurocognitive functioning and neuromaturation. METHOD: A sample of 831 youth, ages 12-21 years, was recruited at five sites across the United States, oversampling those at risk for alcohol use problems. Most (83%) had limited or no history of alcohol or other drug use, and a smaller portion (17%) exceeded drinking thresholds. A comprehensive assessment of biological development, family background, psychiatric symptomatology, and neuropsychological functioning-in addition to anatomical, diffusion, and functional brain magnetic resonance imaging-was completed at baseline. RESULTS: The NCANDA sample of youth is nationally representative of sex and racial/ethnic groups. More than 50% have at least one risk characteristic for subsequent heavy drinking (e.g., family history, internalizing or externalizing symptoms). As expected, those who exceeded drinking thresholds (n = 139) differ from those who did not (n = 692) on identified factors associated with early alcohol use and problems. CONCLUSIONS: NCANDA successfully recruited a large sample of adolescents and comprehensively assessed psychosocial functioning across multiple domains. Based on the sample's risk profile, NCANDA is well positioned to capture the transition into drinking and alcohol problems in a large portion of the cohort, as well as to help disentangle the associations between alcohol use, neurobiological maturation, and neurocognitive development and functioning. PMID- 26562599 TI - Marijuana and Other Substance Use Among Motor Vehicle Operators: A Latent Class Analysis. AB - OBJECTIVE: The deleterious effect of multiple-substance use on driving performance is well established, but relatively little research has examined the patterns of drug use among multiple-substance users and its relationship to both alcohol use and adverse driving outcomes. METHOD: The current study used latent class analysis to examine subgroups of substance users among a population of drivers who screened positively for 2 or more of 13 substances other than alcohol (N = 250). A series of logistic regression analyses was conducted to examine demographic predictors of latent class assignment and class association with adverse driving outcomes. RESULTS: Four distinct subclasses of users were identified among multiple-substance-using drivers: Class 1 consisted of individuals who demonstrated high levels of all substances indicators (5%). The second class demonstrated high levels of marijuana and cocaine use and lower levels of all other substances (27%). The third class screened high for marijuana and nonmedical prescription opiate analgesics use (36%), whereas the last class demonstrated high nonmedical prescription opiate analgesics and benzodiazepine use (32%). Drivers in Class 2 (marijuana and cocaine users) were more likely to be younger and have a positive breath alcohol concentration than drivers in any other class. CONCLUSIONS: Because multidrug users show dissimilar characteristics, the propensity of researchers to lump all multiple-substance users together may either erroneously attribute the potentially profound impact of those in the marijuana and cocaine use class to all multiple-substance users or dilute their specific contribution to crash risk. PMID- 26562600 TI - Clubbing With Familiar Social Groups: Relaxed Vigilance and Implications for Risk. AB - OBJECTIVE: This research examined the relationship between the intragroup familiarity among peers visiting nightclubs and the likelihood of experiencing negative outcomes. We hypothesized, based on our prior work, that members who are more familiar with their group would be more likely to experience sexual and physical aggression while at the club. METHOD: The study involved 1,765 young adults (within 654 natural groups) sampled at nightclubs in the San Francisco Bay area. Participants were interviewed about their clubbing history and expectations before entering the club and about their experiences in the club as they exited. Breath samples were collected at both entry and exit to obtain objective measures of alcohol use. RESULTS: Using generalized linear mixed modeling to accommodate correlated data, we found that, to the extent that club patrons were familiar with more of their peer group, the more likely they were to experience sexual and physical aggression, although this was moderated by participant gender. CONCLUSIONS: Although in many circumstances group cohesion can be a protective factor, the results of this study suggest that greater group familiarity might sometimes be associated with less concern for safety, reduced vigilance, and an increase in negative experiences. PMID- 26562601 TI - Sex Differences in the Personality and Cognitive Characteristics of First-Time DWI Offenders. AB - OBJECTIVE: Driving while impaired by alcohol (DWI) is a significant yet preventable public health problem. The overrepresentation of males among DWI offenders has been attributed in part to greater sensation seeking and impulsivity features in males, although recent evidence points to increasing female DWI events. Studies exploring sex differences in DWI to better understand and intervene in these trends are rare and often methodologically lacking. This study examined sex differences among first-time DWI offenders by testing the hypotheses that, compared with non-DWI drivers, male offending is primarily associated with greater impulsive and sensation-seeking personality features and response disinhibition, whereas female offending is primarily associated with greater alcohol misuse. METHOD: Male and female drivers ages 18-44 years convicted of a first DWI offense (n = 217) and non-DWI driver controls (n = 79) were recruited and compared on measures of psychosocial characteristics, substance use, personality, and response inhibition. RESULTS: In partial support of our hypotheses, greater alcohol misuse severity was found in female DWI offenders compared with female non-DWI drivers but an equivalent effect was not detected in males. Counter to hypothesis, greater impulsivity, sensation seeking, and response disinhibition were not found in male non-DWI drivers compared with male non-DWI drivers. Unexpectedly, greater impulsivity was found in female DWI offenders compared with female DWI drivers. CONCLUSIONS: Little evidence was found for impulsivity, sensation seeking, and response disinhibition being factors that directly explain higher rates of DWI offending in males. In contrast, more marked alcohol misuse and trait impulsivity in female DWI drivers suggest a greater vulnerability to uncontrolled drinking leading to dangerous driving. These findings represent a basis for examining sex-related responsivity to distinct approaches to DWI prevention. PMID- 26562603 TI - Implementation of Electronic Health Records and Entrepreneurial Strategic Orientation in Substance Use Disorder Treatment Organizations. AB - OBJECTIVE: This research studied the relationships of the components of entrepreneurial strategic orientation (ESO) with implementation of electronic health records (EHRs) within organizations that treat patients with substance use disorders (SUDs). METHOD: A national sample of 317 SUD treatment providers were studied in a period after the Health Information Technology for Economic and Clinical Health (HITECH) Act was enacted (2009) and meaningful use EHR requirements were established (2010), but before implementation of the Affordable Care Act. The study sample was selected using stratified random sampling and was part of a longitudinal study of treatment providers across the United States. RESULTS: After we controlled for potentially confounding variables, four components of ESO had a significant relationship with EHR implementation. Levels of slack resources in an organization moderated the relationship of ESO with meaningful use of EHRs, increasing the strength of the relationship for some components but reducing the strength of others. CONCLUSIONS: From a policy and practice perspective, the results suggest that training and education to develop higher levels of ESO within SUD treatment organizations are likely to increase their level of meaningful use of EHRs, which in turn may enhance the integration of SUD treatment with primary medical providers, better preparing SUD treatment providers for the environmental changes of the Affordable Care Act. PMID- 26562602 TI - Predictors of Abstinence From Heavy Drinking During Follow-Up in COMBINE. AB - OBJECTIVE: Although the primary focus of clinical trials is on between-group comparisons during treatment, these studies can also yield insights into which patient characteristics predict longer term outcomes. Our goal was to identify predictors of good outcome during the 1-year follow-up in the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study. METHOD: We constructed classification trees and a deterministic forest to predict no heavy drinking days during the last 8 weeks of the 1-year follow-up in COMBINE, based on more than 100 baseline predictors and drinking outcomes during the treatment phase of the study. The COMBINE sample was randomly split into a training and a validation data set. Logistic regression models were fit to compare the predictive performance of tree-based methods and classical methods. RESULTS: A small tree with only two splits and four nodes based on abstinence and good clinical outcome during treatment had fair classification accuracy in the training and the validation samples: area under the curve (AUC) of 71% and 70%, respectively. Drinking outcomes during treatment were the strongest predictors in the deterministic forest. Logistic regression analyses based on four main effects (good clinical outcome, level of drinking during treatment, age at onset of alcohol dependence, and feeling more energetic) had slightly better classification accuracy (AUC = 74%). CONCLUSIONS: End-of-treatment outcomes were the strongest predictors of long-term outcome in all analyses. The results emphasize the importance of optimizing outcomes during treatment and identify potential subgroups of individuals who require additional or alternative interventions to achieve good long-term outcome. PMID- 26562604 TI - Alcohol Doesn't Always Compromise Cognitive Function: Exploring Moderate Doses in Young Adults. AB - OBJECTIVE: The purpose of this study was to clarify inconsistent findings regarding the acute cognitive effects of subintoxicating alcohol doses (i.e., <80 mg/dl) by controlling for and evaluating variables that might modulate dose related outcomes. METHOD: The current study examined the effects of sex/gender and alcohol concentration on select cognitive functions in 94 individuals (49 men) between 25 and 35 years of age. Participants were randomly assigned to one of three dose conditions: target peak breath alcohol concentration of 0 mg/dl (placebo), 40 mg/dl (low), or 65 mg/dl (moderate). After beverage consumption, they completed tasks assessing psychomotor, set-shifting, and working memory ability. RESULTS: Analyses revealed no significant effect of dose for any cognitive domain. A trend-level effect of dose on psychomotor performance was observed, with the low-dose group performing somewhat better than the moderate dose and placebo groups. No sex main effects or interactions were revealed. CONCLUSIONS: Consistent with our previous studies, these data suggest that low and moderate doses of alcohol may not compromise cognitive ability in non-problem drinkers under certain task conditions. Given the outcomes, sex differences cannot be meaningfully addressed. Future consideration of potentially influential variables and assessment of similarly well-defined cohorts might yield a clearer interpretation of alcohol's behavioral consequences. PMID- 26562605 TI - Decomposing the Relationship Between Anxiety Sensitivity and Alcohol Use. AB - OBJECTIVE: The misuse of alcohol is related to numerous detrimental health effects. Research has determined anxiety sensitivity (AS) to be a risk factor for problematic alcohol use. To date, no studies have investigated this relationship using a bifactor model of AS. This study used a bifactor model to determine the effects of the general AS factor and the cognitive, physical, and social concerns subfactors on alcohol-related outcomes. METHOD: The sample consisted of 329 participants selected from a larger sample of individuals in a brief smoking cessation intervention. Latent factor models were used to determine the effects of the bifactor model of AS on alcohol use behavior. RESULTS: The general AS factor was significantly associated with alcohol use problems but not alcohol consumption. The AS subfactors of cognitive, physical, and social concerns were not significantly related to either alcohol variable. CONCLUSIONS: The findings are inconsistent with previous research that has found associations between the AS subfactors and alcohol-related outcomes. The use of a bifactor model of AS allowed the variance associated with AS to be parceled out of the subfactors, indicating that general AS accounts for the relationship between AS and alcohol misuse. PMID- 26562607 TI - Drinking Motives Moderate the Effect of the Social Environment on Alcohol Use: An Event-Level Study Among Young Adults. AB - OBJECTIVE: The purpose of this study was to test (a) whether drinking motives predict event-level drinking on weekend evenings; (b) whether the number of friends present in social situations was associated with drinking on weekend evenings; and (c) whether drinking motives moderate the association between friends present and drinking. METHOD: We linked individual-level drinking motives (measured at baseline) to event-level data assessed every Thursday, Friday, and Saturday evening over 5 weeks. The number of drinks and male and female friends present in the situation were assessed at 9 p.m., 10 p.m., 11 p.m., midnight, and 1 a.m. In total, 197 young adults (51.3% male) completed 11,516 event-level assessments. RESULTS: Multilevel models by gender revealed that higher enhancement motives predicted a greater number of drinks consumed in a given moment, but only among women. The higher the number of male and female friends present in a situation, the more drinks consumed by both genders. Last, drinking motives moderated the association between the number of friends present and the number of drinks. For women, higher enhancement motives predicted more drinks in situations with more male friends. For men, higher coping motives predicted more drinks in situations with no friends and in situations with more female friends. Lower coping motives predicted more drinks with more male friends. Higher conformity motives predicted fewer drinks with more female friends. CONCLUSIONS: Drinking motives appear to moderate event-level factors rather than directly predict drinking on weekend evenings. Depending on the motives for drinking, event-level factors (e.g., friends present in a situation) have a strong effect on an individual's drinking. PMID- 26562606 TI - Dynamic Patterns of Adolescent Substance Use: Results From a Nationally Representative Sample of High School Students. AB - OBJECTIVE: Use of tobacco, alcohol, marijuana, and other drugs increases during the high school years, yet little is known about individual patterns over time, particularly patterns of contemporaneous multiple-substance use. This study examined trajectories of contemporaneous substance use and how individual and social factors differentially predict patterns of substance use. METHOD: Longitudinal trajectories of substance use were examined in a nationally representative sample of students (N = 2,512) over a 3-year period (10th through 12th grades) using latent class analysis. Individual, parental, and peer risk factors in 10th grade were examined in relation to membership in trajectory classes. RESULT: A five-class model was identified: nonusers (45.5%); tobacco, alcohol, and other drug users (9.2%); alcohol and other drug users (9.2%); increasing multiple-substance users (16.7%); and decreasing multiple-substance users (19.4%). Depressive symptoms at baseline were associated with a higher likelihood of membership in all classes except the increasing multiple-substance user class, but the association becomes insignificant when social influence factors were adjusted. Parental-monitoring knowledge was associated with a lower likelihood of membership in all classes except increasing multiple-substance-user class, whereas perceived parental disapproval was associated with a lower likelihood of membership in the tobacco, alcohol, and other drug user class. Peer substance use was associated with a higher likelihood of membership in each of the substance use classes. CONCLUSIONS: The identified longitudinal profiles highlight the pervasiveness and dynamic patterns of contemporaneous multiple substance use during 10th through 12th grades. Negative peer influence increased risk, whereas positive parenting behaviors decreased risk. The findings are consistent with the need to foster social influences and protective factors against adolescent substance use. PMID- 26562608 TI - The Hidden Role of the Alcohol Industry in Youth Drinking in Brazil. PMID- 26562609 TI - Fine-Tuning Nickel Phenoxyimine Olefin Polymerization Catalysts: Performance Boosting by Alkali Cations. AB - To gain a better understanding of the influence of cationic additives on coordination-insertion polymerization and to leverage this knowledge in the construction of enhanced olefin polymerization catalysts, we have synthesized a new family of nickel phenoxyimine-polyethylene glycol complexes (NiL0, NiL2-NiL4) that form discrete molecular species with alkali metal ions (M(+) = Li(+), Na(+), K(+)). Metal binding titration studies and structural characterization by X-ray crystallography provide evidence for the self-assembly of both 1:1 and 2:1 NiL:M(+) species in solution, except for NiL4/Na(+) which form only the 1:1 complex. It was found that upon treatment with a phosphine scavenger, these NiL complexes are active catalysts for ethylene polymerization. We demonstrate that the addition of M(+) to NiL can result in up to a 20-fold increase in catalytic efficiency as well as enhancement in polymer molecular weight and branching frequency compared to the use of NiL without coadditives. To the best of our knowledge, this work provides the first systematic study of the effect of secondary metal ions on metal-catalyzed polymerization processes and offers a new general design strategy for developing the next generation of high performance olefin polymerization catalysts. PMID- 26562610 TI - Direct C-H Trifluoromethylation of Glycals by Photoredox Catalysis. AB - A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemoto's reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly. This visible light-mediated trifluoromethylation reaction was highlighted by the trifluoromethylation of the biologically important Neu2en moiety. PMID- 26562611 TI - Plantadeprate A, a Tricyclic Monoterpene Zwitterionic Guanidium, and Related Derivatives from the Seeds of Plantago depressa. AB - Two new alkaloids, plantadeprate A (1) and 1'-(4"-hydroxybutyl)plantagoguanidinic acid (2), along with three known compounds, were isolated from the seeds of Plantago depressa. Their structures were elucidated by physical data analyses including NMR, MS, and electronic circular dichroism (ECD) methods. Plantadeprate A (1), a monoterpene zwitterionic guanidium, possesses a unique 5/5/6-tricyclic ring system. Its absolute configuration was determined by X-ray crystallography and computational methods. Compound 1, plumbagine D (3), and plantagoguanidinic acid (4) exhibited potential antihyperglycemic properties attributed to suppression of hepatic gluconeogenesis with inhibitory rates of 8.2%, 18.5%, and 12.5% at 40 MUM, respectively. PMID- 26562613 TI - Application of Ga(68) -DOTA-exendin-4 PET/CT to localize an occult insulinoma. PMID- 26562612 TI - TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis. AB - BACKGROUND: Over 550,000 sinus surgeries are performed annually in the United States on patients with chronic rhinosinusitis (CRS). Although the results of sinus surgery vary widely, no known genetic factor has been identified to predict surgical outcomes. The bitter taste receptor T2R38 has recently been demonstrated to regulate upper airway innate defense and may affect patient responses to therapy. Our goal was to determine whether TAS2R38 genetics predicts outcomes in CRS patients following sinus surgery. METHODS: A prospective study of patients undergoing sinus surgery evaluating postoperative outcomes through the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were genotyped for TAS2R38. RESULTS: A total of 123 patients with CRS were initially analyzed; 82 patients showed nasal polyps (CRSwNP) and 41 patients were without nasal polyps (CRSsNP). Six months after surgery, the overall SNOT-22 improvement was 25 +/- 23 points. The TAS2R38 genotype was found to significantly correlate with surgical outcomes in patients without polyps; homozygotes for the functional receptor had a mean improvement of 38 +/- 21, whereas heterozygotes or homozygotes for the nonfunctional receptor had a mean improvement of 12 +/- 22 (p = 0.006). This result was confirmed with a multivariate regression that incorporated further patients with 1-month and 3-month scores (n = 207). CONCLUSION: In patients undergoing sinus surgery for CRS, we have identified a genetic polymorphism that predicts variability in quality of life improvement following surgery at 6 months in nonpolypoid CRS. This is the first genetic polymorphism identified that has demonstrated to predict surgical outcome for a select group of CRS patients. PMID- 26562614 TI - NEB-related core-rod myopathy with distinct clinical and pathological features. AB - INTRODUCTION: Mutations in the gene encoding nebulin (NEB) are known to cause several types of congenital myopathy including recessive nemaline myopathy and distal nebulin myopathy. Core-rod myopathy has recently been reported to be another type of NEB-related myopathy, and is pathologically characterized by the coexistence of cores and nemaline rods within muscle fibers. METHODS: We describe 2 patients with core-rod myopathy who were analyzed genetically by whole exome sequencing and evaluated clinically and pathologically. Findings were compared with those of patients with the disease of other genetic causes. RESULTS: Three NEB mutations were identified, 2 of which were novel. Mild clinical features, unusual patterns of muscle involvement, and atypical pathological findings were observed. CONCLUSIONS: We propose that the clinical and pathological spectrum of core-rod myopathy should be widened. A significant amount of residual nebulin expression is believed to contribute to the much milder phenotype exhibited by the patients we describe here. PMID- 26562616 TI - NMR Investigations of Noncovalent Carbon Tetrel Bonds. Computational Assessment and Initial Experimental Observation. AB - Group IV tetrel elements may act as tetrel bond donors, whereby a region of positive electrostatic potential (sigma-hole) interacts with a Lewis base. The results of calculations of NMR parameters are reported for a series of model compounds exhibiting tetrel bonding from a methyl carbon to the oxygen or nitrogen atoms in various functional groups. The (13)C chemical shift (deltaiso) and the (1c)J((13)C,Y) coupling (Y = (17)O, (15)N) across the tetrel bond are recorded as a function of geometry. The sensitivity of the NMR parameters to the noncovalent interaction is demonstrated via an increase in deltaiso and in |(1c)J((13)C,Y)| as the tetrel bond shortens. Gauge-including projector-augmented wave density functional theory (DFT) calculations of deltaiso are reported for crystals that exhibit tetrel bonding in the solid state. Experimental deltaiso values for solid sarcosine and its tetrel-bonded salts corroborate the computational findings. This work offers new insights into tetrel bonding and facilitates the incorporation of tetrel bonds as restraints in NMR crystallographic structure refinement. PMID- 26562617 TI - Assessment of DFT for Computing Sum Frequency Generation Spectra of an Epoxydiol and a Deuterated Isotopologue at Fused Silica/Vapor Interfaces. AB - We assess the capabilities of eight popular density functional theory (DFT) functionals, in combination with several basis sets, as applied to calculations of vibrational sum frequency generation (SFG) spectra of the atmospherically relevant isoprene oxidation product trans-beta-isoprene epoxydiol (IEPOX) and one of its deuterated isotopologues at the fused silica/vapor interface. We use sum of squared differences (SSD) and total absolute error (TAE) calculations to estimate the performance of each functional/basis set combination in producing SFG spectra that match experimentally obtained spectra from trans-beta-IEPOX and one of its isotopologues. Our joined SSD/TAE analysis shows that while the twist angle of the methyl C3v symmetry axis of trans-beta-IEPOX relative to the surface is sensitive to the choice of DFT functional, the calculated tilt angle relative to the surface normal is largely independent of the functional and basis set. Moreover, we report that hybrid functionals such as B3LYP, omegaB97X-D, PBE0, and B97-1 in combination with a modest basis set, such as 6-311G(d,p), provides good agreement with experimental data and much better performance than pure functionals such as PBE and BP86. However, improving the quality of the basis set only improves agreement with experimental data for calculations based on pure functionals. A conformational analysis, based on comparisons of calculated and experimental SFG spectra, suggests that trans-beta-IEPOX points all of its oxygen atoms toward the silica/vapor interface. PMID- 26562618 TI - The 'impurity' of indoor air. PMID- 26562615 TI - Molecular mechanisms of midfacial developmental defects. AB - The morphogenesis of midfacial processes requires the coordination of a variety of cellular functions of both mesenchymal and epithelial cells to develop complex structures. Any failure or delay in midfacial development as well as any abnormal fusion of the medial and lateral nasal and maxillary prominences will result in developmental defects in the midface with a varying degree of severity, including cleft, hypoplasia, and midline expansion. Despite the advances in human genome sequencing technology, the causes of nearly 70% of all birth defects, which include midfacial development defects, remain unknown. Recent studies in animal models have highlighted the importance of specific signaling cascades and genetic environmental interactions in the development of the midfacial region. This review will summarize the current understanding of the morphogenetic processes and molecular mechanisms underlying midfacial birth defects based on mouse models with midfacial developmental abnormalities. PMID- 26562619 TI - Quantum Confined Stark Effect in a GaAs/AlGaAs Nanowire Quantum Well Tube Device: Probing Exciton Localization. AB - In this Letter, we explore the nature of exciton localization in single GaAs/AlGaAs nanowire quantum well tube (QWT) devices using photocurrent (PC) spectroscopy combined with simultaneous photoluminescence (PL) and photoluminescence excitation (PLE) measurements. Excitons confined to GaAs quantum well tubes of 8 and 4 nm widths embedded into an AlGaAs barrier are seen to ionize at high bias levels. Spectroscopic signatures of the ground and excited states confined to the QWT seen in PL, PLE, and PC data are consistent with simple numerical calculations. The demonstration of good electrical contact with the QWTs enables the study of Stark effect shifts in the sharp emission lines of excitons localized to quantum dot-like states within the QWT. Atomic resolution cross-sectional TEM measurements and an analysis of the quantum confined Stark effect of these dots provide insights into the nature of the exciton localization in these nanostructures. PMID- 26562620 TI - Electron Transfer and Associative Detachment in Low-Temperature Collisions of D( ) with H. AB - The interaction of D(-) with H was studied experimentally and theoretically at low temperatures. The rate coefficients of associative detachment and electron transfer reactions were measured in the temperature range 10-160 K using a combination of a cryogenic 22-pole trap with a cold effusive beam of atomic hydrogen. Results from quantum-mechanical calculations are in good agreement with the experimental data. The rate coefficient obtained for electron transfer is increasing monotonically with temperature from 1 * 10(-9) cm(3) s(-1) at 10 K to 5 * 10(-9) cm(3) s(-1) at 160 K. The rate coefficient for associative detachment has a flat maximum of 3 * 10(-9) cm(3) s(-1) between 30 and 100 K. PMID- 26562622 TI - Measuring antigen presentation in mouse brain endothelial cells ex vivo and in vitro. AB - We have recently demonstrated that brain endothelial cells cross-present parasite antigen during mouse experimental cerebral malaria (ECM). Here we describe a 2-d protocol to detect cross-presentation by isolating the brain microvessels and incubating them with a reporter cell line that expresses lacZ upon detection of the relevant peptide-major histocompatibility complex. After X-gal staining, a typical positive result consists of hundreds of blue spots, compared with fewer than 20 spots from a naive brain. The assay is generalizable to other disease contexts by using reporter cells that express appropriate specific T cell receptors. Also described is the protocol for culturing endothelial cells from brain microvessels isolated from naive mice. After 7-10 d, an in vitro cross presentation assay can be performed by adding interferon-gamma, antigen (e.g., Plasmodium berghei-infected red blood cells) and reporter cells in sequence over 3 d. This is useful for comparing different antigen forms or for probing the effects of various interventions. PMID- 26562621 TI - Next-generation diagnostics and disease-gene discovery with the Exomiser. AB - Exomiser is an application that prioritizes genes and variants in next-generation sequencing (NGS) projects for novel disease-gene discovery or differential diagnostics of Mendelian disease. Exomiser comprises a suite of algorithms for prioritizing exome sequences using random-walk analysis of protein interaction networks, clinical relevance and cross-species phenotype comparisons, as well as a wide range of other computational filters for variant frequency, predicted pathogenicity and pedigree analysis. In this protocol, we provide a detailed explanation of how to install Exomiser and use it to prioritize exome sequences in a number of scenarios. Exomiser requires ~3 GB of RAM and roughly 15-90 s of computing time on a standard desktop computer to analyze a variant call format (VCF) file. Exomiser is freely available for academic use from http://www.sanger.ac.uk/science/tools/exomiser. PMID- 26562623 TI - Traumatic brain injury in U.S. Veterans with traumatic spinal cord injury. AB - Patients with both a spinal cord injury (SCI) and traumatic brain injury (TBI) are often very difficult to manage and can strain the resources of clinical units specialized in treating either diagnosis. However, a wide range of estimates exists on the extent of this problem. The aim of this study was to describe the scope of the problem in a well-defined population attending a comprehensive SCI unit. Electronic medical records of all patients with SCI being followed by the SCI unit in a U.S. Veterans' hospital were searched to identify those with concurrent TBI. The data were analyzed for age, sex, cause of injury, level and completeness of SCI, cognitive impairment, relationship with Active Duty military, and date of injury. Of 409 Veterans with a traumatic SCI, 99 (24.2%) were identified as having had a concurrent TBI. The occurrence did not appear to be closely related to military conflict. Reports of TBI were much more common in the last 20 yr than in previous decades. Documentation of TBI in patients with SCI was inconsistent. Improved screening and documentation could identify all patients with this dual diagnosis and facilitate appropriate management. PMID- 26562624 TI - Gender Differences in Posttraumatic Stress Disorder and Help Seeking in the U.S. Army. AB - BACKGROUND: Inconsistent findings between studies of gender differences in mental health outcomes in military samples have left open questions of differential prevalence in posttraumatic stress disorder (PTSD) among all United States Army soldiers and in differential psychosocial and comorbid risk and protective factor profiles and their association with receipt of treatment. METHODS: This study assesses the prevalence and risk factors of screening positive for PTSD for men and women based on two large, population-based Army samples obtained as part of the 2005 and 2008 U.S. Department of Defense Surveys of Health Related Behaviors among Active Duty Military Personnel. RESULTS: The study showed that overall rates of PTSD, as measured by several cutoffs of the PTSD Checklist, are similar between active duty men and women, with rates increasing in both men and women between the two study time points. Depression and problem alcohol use were strongly associated with a positive PTSD screen in both genders, and combat exposure was significantly associated with a positive PTSD screen in men. Overall, active duty men and women who met criteria for PTSD were equally likely to receive mental health counseling or treatment, though gender differences in treatment receipt varied by age, race, social support (presence of spouse at duty station), history of sexual abuse, illness, depression, alcohol use, and combat exposure. CONCLUSIONS: The study demonstrates that the prevalence of PTSD as well as the overall utilization of mental health services is similar for active duty men compared with women. However, there are significant gender differences in predictors of positive PTSD screens and receipt of PTSD treatment. PMID- 26562625 TI - Assessment of Muscle Contractile Properties at Acute Moderate Altitude Through Tensiomyography. AB - Under hypoxia, alterations in muscle contractile properties and faster fatigue development have been reported. This study investigated the efficacy of tensiomyography (TMG) in assessing muscle contractile function at acute moderate altitude. Biceps femoris (BF) and vastus lateralis (VL) muscles of 18 athletes (age 20.1 +/- 6.1 years; body mass 65.4 +/- 13.9 kg; height 174.6 +/- 9.5 cm) were assessed at sea level and moderate altitude using electrically evoked contractions on two consecutive days. Maximum radial displacement (Dm), time of contraction (Tc), reaction time (Td), sustained contraction time (Ts), and relaxation time (Tr) were recorded at 40, 60, 80, and 100 mA. At altitude, VL showed lower Dm values at 40 mA (p = 0.008; ES = -0.237). Biceps femoris showed Dm decrements in all electrical stimulations (p < 0.001, ES > 0.61). In VL, Tc was longer at altitude at 40 (p = 0.031, ES = 0.56), and 100 mA (p = 0.03, ES = 0.51). Regarding Td, VL showed significant increases in all electrical intensities under hypoxia (p <= 0.03, ES >= 0.33). TMG appears effective at detecting slight changes in the muscle contractile properties at moderate altitude. Further research involving TMG along with other muscle function assessment methods is needed to provide additional insight into peripheral neuromuscular alterations at moderate altitude. PMID- 26562626 TI - Understanding the Molecular Basis of Heterogeneity in Induced Pluripotent Stem Cells. AB - Reprogramming of somatic cells to generate induced pluripotent stem cells (iPSCs) has considerable latency and generates epigenetically distinct partially and fully reprogrammed clones. To understand the molecular basis of reprogramming and to distinguish the partially reprogrammed iPSC clones (pre-iPSCs), we analyzed several of these clones for their molecular signatures. Using a combination of markers that are expressed at different stages of reprogramming, we found that the partially reprogrammed stable clones have significant morphological and molecular heterogeneity in their response to transition to the fully pluripotent state. The pre-iPSCs had significant levels of OCT4 expression but exhibited variable levels of mesenchymal-to-epithelial transition. These novel molecular signatures that we identified would help in using these cells to understand the molecular mechanisms in the late of stages of reprogramming. Although morphologically similar mouse iPSC clones showed significant heterogeneity, the human iPSC clones isolated initially on the basis of morphology were highly homogeneous with respect to the levels of pluripotency. PMID- 26562627 TI - A Phosphotyrosine Switch Controls the Association of Histone Mark Readers with Methylated Proteins. AB - Although histone post-translational modifications play a paramount role in controlling access to genetic information, our understanding of the precise mechanisms regulating chromatin signaling remains superficial. For instance, histone H3 trimethylated on lysine 9 (H3K9(me3)) favors the association of chromodomain proteins such as heterochromatin protein 1alpha (HP1alpha) with chromatin. However, HP1alpha and other such chromatin proteins are not covering all specific histone marks at all times. Thus, how are these reader-histone interactions regulated? We propose tyrosine phosphorylation within the aromatic cage of histone mark readers as a molecular switch that can either turn ON or OFF and even alter the specificity of reader-histone interactions. We have identified tyrosine phosphorylation events on the chromatin proteins HP1alpha and M-phase phosphoprotein 8 that regulate their association with methylated histones in vitro (synthetic peptides, calf thymus purified histones, and nucleosomes), but also in cells, thus controlling access to genetic information. PMID- 26562628 TI - Is there a role for targeted medical therapies in patients with craniopharyngiomas? PMID- 26562629 TI - Site of Fluid Secretion in Small Airways. AB - The secretion and management of readily transportable airway surface liquid (ASL) along the respiratory tract is crucial for the clearance of debris and pathogens from the lungs. In proximal large airways, submucosal glands (SMGs) can produce ASL. However, in distal small airways, SMGs are absent, although the lumens of these airways are, uniquely, highly plicated. Little is known about the production and maintenance of ASL in small airways, but using electrophysiology, we recently found that native porcine small airways simultaneously secrete and absorb. How these airways can concurrently transport ASL in opposite directions is puzzling. Using high expression of the Na-K-2Cl cotransport (NKCC) 1 protein (SLC12a2) as a phenotypic marker for fluid secretory cells, immunofluorescence microscopy of porcine small airways revealed two morphologically separated sets of luminal epithelial cells. NKCC1 was abundantly expressed by most cells in the contraluminal regions of the pleats but highly expressed very infrequently by cells in the luminal folds of the epithelial plications. In larger proximal airways, the acini of SMGs expressed NKCC1 prominently, but cells expressing NKCC1 in the surface epithelium were sparse. Our findings indicate that, in the small airway, cells in the pleats of the epithelium secrete ASL, whereas, in the larger proximal airways, SMGs mainly secrete ASL. We propose a mechanism in which the locations of secretory cells in the base of pleats and of absorptive cells in luminal folds physically help maintain a constant volume of ASL in small airways. PMID- 26562630 TI - Self-powered switch-controlled nucleic acid extraction system. AB - Over the past few decades, lab-on-a-chip (LOC) technologies have played a great role in revolutionizing the way in vitro medical diagnostics are conducted and transforming bulky and expensive laboratory instruments and labour-intensive tests into easy to use, cost-effective miniaturized systems with faster analysis time, which can be used for near-patient or point-of-care (POC) tests. Fluidic pumps and valves are among the key components for LOC systems; however, they often require on-line electrical power or batteries and make the whole system bulky and complex, therefore limiting its application to POC testing especially in low-resource setting. This is particularly problematic for molecular diagnostics where multi-step sample processing (e.g. lysing, washing, elution) is necessary. In this work, we have developed a self-powered switch-controlled nucleic acid extraction system (SSNES). The main components of SSNES are a powerless vacuum actuator using two disposable syringes and a switchgear made of PMMA blocks and an O-ring. In the vacuum actuator, an opened syringe and a blocked syringe are bound together and act as a working syringe and an actuating syringe, respectively. The negative pressure in the opened syringe is generated by a restoring force of the compressed air inside the blocked syringe and utilized as the vacuum source. The Venus symbol shape of the switchgear provides multiple functions including being a reagent reservoir, a push-button for the vacuum actuator, and an on-off valve. The SSNES consists of three sets of vacuum actuators, switchgears and microfluidic components. The entire system can be easily fabricated and is fully disposable. We have successfully demonstrated DNA extraction from a urine sample using a dimethyl adipimidate (DMA)-based extraction method and the performance of the DNA extraction has been confirmed by genetic (HRAS) analysis of DNA biomarkers from the extracted DNAs using the SSNES. Therefore, the SSNES can be widely used as a powerless and disposable system for DNA extraction and the syringe-based vacuum actuator would be easily utilized for diverse applications with various microchannels as a powerless fluidic pump. PMID- 26562631 TI - Stem cell-based approaches in dentistry. AB - Repair of dental pulp and periodontal lesions remains a major clinical challenge. Classical dental treatments require the use of specialised tissue-adapted materials with still questionable efficacy and durability. Stem cell-based therapeutic approaches could offer an attractive alternative in dentistry since they can promise physiologically improved structural and functional outcomes. These therapies necessitate a sufficient number of specific stem cell populations for implantation. Dental mesenchymal stem cells can be easily isolated and are amenable to in vitro expansion while retaining their stemness. In vivo studies realised in small and large animals have evidenced the potential of dental mesenchymal stem cells to promote pulp and periodontal regeneration, but have also underlined new important challenges. The homogeneity of stem cell populations and their quality control, the delivery method, the quality of the regenerated dental tissues and their integration to the host tissue are some of the key challenges. The use of bioactive scaffolds that can elicit effective tissue repair response, through activation and mobilisation of endogenous stem cell populations, constitutes another emerging therapeutic strategy. Finally, the use of stem cells and induced pluripotent cells for the regeneration of entire teeth represents a novel promising alternative to dental implant treatment after tooth loss. In this mini-review, we present the currently applied techniques in restorative dentistry and the various attempts that are made to bridge gaps in knowledge regarding treatment strategies by translating basic stem cell research into the dental practice. PMID- 26562633 TI - Bilateral Mucopyocele of the Torus Tubarius Presenting as Headache. PMID- 26562632 TI - Variability of Ocular Deviation in Strabismus. AB - IMPORTANCE: In strabismus, the fixating eye conveys the direction of gaze while the fellow eye points at a peripheral location in space. The stability of the eyes may be reduced by the absence of a common target. OBJECTIVE: To quantify the stability of eye position in strabismus and to measure variability in the ocular deviation. DESIGN, SETTING, AND PARTICIPANTS: From 2010 to 2014, a prospective comparative case study of 25 patients with alternating exotropia with normal visual acuity in each eye and 25 control individuals was conducted in a laboratory at a tertiary eye center. A video eye tracker was used to measure the position of each eye while participants alternated fixation on the center of a cross under dichoptic conditions or scanned pictures of natural scenes. MAIN OUTCOMES AND MEASURES: Spatial and temporal variability in the position of the fixating eye and the nonfixating eye in patients with strabismus and control individuals, quantified by the log area of ellipses containing 95% of eye positions or mean SDs of eye position. RESULTS: In the 25 patients with strabismus, the mean (SD) age was 28 (14) years (range, 8-55 years) and the mean (SD) ocular deviation was 14.2 degrees (5.9 degrees ) (range, 4.4 degrees -22.4 degrees ). In the patients with strabismus, the mean position variability (1.80 log units; 95% CI, 1.66-1.93) for the deviating eye was greater than for the fixating eye (1.26 log units; 95% CI, 1.17-1.35) (P < .001). The fixating eye of patients with strabismus was more variable in position than the fixating eye of individuals without strabismus (0.98 log units; 95% CI, 0.88-1.08) (P < .005). CONCLUSIONS AND RELEVANCE: In patients with strabismus, even without amblyopia, the deviated eye is more variable in position than the fixating eye. Both eyes are less stable in position than the eyes of control individuals, which indicates that strabismus impairs the ability to fixate targets steadily. Saccades contribute to variability of the deviation angle because they are less conjugate in patients with strabismus. PMID- 26562634 TI - The timing of life history events in the presence of soft disturbances. AB - We study a model for the evolutionarily stable strategy (ESS) used by biological populations for choosing the time of life-history events, such as arrival from migration and breeding. In our model we account for both intra-species competition (early individuals have a competitive advantage) and a disturbance which strikes at a random time, killing a fraction 1-p of the population. Disturbances include spells of bad weather, such as freezing or heavily raining days. It has been shown by Iwasa and Levin (1995) that when the disturbance is so strong that it kills any individual present when it strikes (hard disturbance, p=0), then the ESS is a mixed strategy (individuals choose their arrival date in an interval of possible dates, according to a certain probability distribution). In this case, individuals wait for a certain time and afterwards start arriving (or breeding) every day. In this paper we explore a biologically more realistic situation whereby the disturbance kills only a fraction of the individuals (soft disturbance, p>0). We also remove some technical assumptions which Iwasa and Levin made on the distribution of the disturbance. We prove that the ESS is still a mixed choice of times, however with respect to the case of hard disturbance, a new phenomenon arises: whenever the disturbance is soft, if the competition is sufficiently strong, the waiting time disappears and a fraction of the population arrives at the earliest day possible, while the rest will arrive throughout the whole period during which the disturbance may occur. This means that under strong competition, the payoff of early arrival balances the increased risk of being killed by the disturbance. We study the behaviour of the ESS and of the average fitness of the population, depending on the parameters involved. We also investigate how the population may be affected by climate change: namely the occurrence of more extreme weather events, which may kill a larger fraction of the population, and time shifts of the distribution of the disturbance. We show how the ESS and the average fitness change under the new climate and discuss which is the impact of the new climate on a population that still follows the old strategy. In particular, we show that, at least under some conditions, extreme weather events imply a temporary decrease of the average fitness of the population due to an increased mortality. In addition, if the population adapts to the new climate, the population may have a larger fitness. PMID- 26562635 TI - Maximal dinucleotide comma-free codes. AB - The problem of retrieval and maintenance of the correct reading frame plays a significant role in RNA transcription. Circular codes, and especially comma-free codes, can help to understand the underlying mechanisms of error-detection in this process. In recent years much attention has been paid to the investigation of trinucleotide circular codes (see, for instance, Fimmel et al., 2014; Fimmel and Strungmann, 2015a; Michel and Pirillo, 2012; Michel et al., 2012, 2008), while dinucleotide codes had been touched on only marginally, even though dinucleotides are associated to important biological functions. Recently, all maximal dinucleotide circular codes were classified (Fimmel et al., 2015; Michel and Pirillo, 2013). The present paper studies maximal dinucleotide comma-free codes and their close connection to maximal dinucleotide circular codes. We give a construction principle for such codes and provide a graphical representation that allows them to be visualized geometrically. Moreover, we compare the results for dinucleotide codes with the corresponding situation for trinucleotide maximal self-complementary C(3)-codes. Finally, the results obtained are discussed with respect to Crick's hypothesis about frame-shift-detecting codes without commas. PMID- 26562636 TI - Integrating Behavioral Health and Primary Care. PMID- 26562637 TI - Primary Care Physicians' Selection of Low-Intensity Treatments for Patients With Depression. AB - BACKGROUND AND OBJECTIVES: Most outpatient treatment for depression is delivered by primary care physicians (PCPs), yet little is known about which patient variables affect PCPs' selection of high-intensity interventions, namely antidepressant medications or psychotherapy, as opposed to less-intensive treatment regimens (eg, watchful waiting, exercise). Our objective was to ascertain whether the patient's symptom severity, presenting psychosocial stress, and lifestyle habits influenced treatment recommendations. METHODS: Forty-two PCPs from six Northeastern US primary care practices provided recommendations in response to vignettes depicting patients with major depressive disorder who varied in symptom severity, psychosocial stressors, and lifestyle habits. RESULTS: Low-intensity-only interventions were recommended less than 25% of the time. Lower symptom severity and higher psychosocial stressors were associated with a greater likelihood of "low-intensity interventions only" recommendations. Less-intensive treatments were rarely recommended without more intensive treatments when the vignettes featured severe depression, whereas they were recommended 39% of the time with vignettes featuring mild/moderate symptoms. In response to the mild/moderate vignettes, the presence of psychosocial stressors led to a decreased likelihood of low-intensity-only recommendations. CONCLUSIONS: Although vignettes depicting depressed patients with mild/moderate symptoms were more likely to elicit low-intensity treatment recommendations, the frequency was still low. Given the evidence that antidepressants and psychotherapy for mild/moderate depression may be no more effective, and likely less cost effective, than low-intensity treatments, the findings suggest a need to disseminate knowledge of less intensive treatment options to primary care physicians. PMID- 26562638 TI - Counseling by Family Physicians: Implications for Training. AB - BACKGROUND AND OBJECTIVES: This study explored family physicians' practice of providing psychosocial interventions in the form of counseling, their beliefs about the efficacy of their counseling, their preferences of who should provide counseling, the skills involved in counseling, and their training experiences in learning how to counsel. METHODS: A total of 230 faculty and residents completed written surveys at 11 family medicine residency programs in Florida. RESULTS: Eighty-one percent of study participants regularly offered counseling to their patients, 85% did so for psychosocial problems, and 94% did so for health behavior change. Compared to residents, faculty reported greater use of counseling and a greater willingness to counsel patients for depression or anxiety. Fifty-six percent of the sample stated that their counseling for mental health problems was effective. Sixty percent reported that their training provided them with a basic knowledge of counseling skills; training involved primarily observing a counselor or acting as a co-counselor with an identified counselor. Cognitive Behavioral Therapy, Motivational Interviewing, and the Stages-of-Change Model were the most widely taught counseling approaches. CONCLUSIONS: Family physicians regularly provide counseling for psychosocial problems and health behavior change, and a modest number believe counseling is effective. Residents counsel less regularly and are less confident in the effectiveness of their counseling compared to faculty. Training in counseling skills generally involves direct observation and learning several counseling techniques. Future research should explore whether models of family physician counseling are practical, which techniques should be taught and how. PMID- 26562639 TI - A Review of Contraception and Abortion Content in Family Medicine Textbooks. AB - BACKGROUND AND OBJECTIVES: Family physicians are critical providers of reproductive health care in the United States, and family physicians and trainees refer to textbooks as a source of clinical information. This study evaluates the coverage of reproductive health topics in current family medicine textbooks. METHODS: We identified 12 common family medicine textbooks through a computerized literature search and through the recommendations of a local family medicine clerkship and evaluated 24 areas of reproductive health content (comprising contraceptive care, management of early pregnancy loss, and provision of induced abortion) for accuracy and thoroughness using criteria that we created based on the latest guidelines. RESULTS: All contraceptive methods evaluated were addressed in more than half of the textbooks, though discrepancies existed by method, with intrauterine devices (IUDs), external (male) condoms, and diaphragms addressed most frequently (10/12 texts) and male and female sterilization addressed least frequently (8/12 texts). While most contraceptive methods, when addressed, were usually addressed accurately, IUDs were often addressed inaccurately. Coverage of early pregnancy loss management was limited to 7/12 texts, and coverage of early abortion methods was even more limited, with only 4/12 texts addressing the topic. CONCLUSIONS: Family medicine textbooks do not uniformly provide correct and thorough information on reproductive health topics relevant to family medicine, and attention is needed to ensure that family physicians are receiving appropriate information and training to meet the reproductive health needs of US women. PMID- 26562640 TI - Directors Recognize Difficulties in Providing Medical Care to Residents But Few Implement Policies to Address Them. AB - BACKGROUND AND OBJECTIVES: Residents find it difficult to access medical care. Some seek care within their own program. Our objectives were to (1) determine whether family medicine program directors see their own resident physicians as patients, (2) describe whether they perceive the residency culture as actively encouraging of this practice, and (3) assess perceptions about reasons to encourage or discourage this. METHODS: We used a paper-based self-administered survey November 2013--January 2014. A stratified random sample of family medicine residencies based on administrative type was used. Participants were directors of sampled programs. The main outcome measure was provision of medical care to resident physicians. RESULTS: A total of 137/250 directors (55%) responded. Thirty (22%) reported seeing residents as patients in their family medicine clinic while 107 did not (78%). Some directors who do see resident patients expressed discomfort in doing so (24%). Participants reported that other faculty physicians were significantly more likely to see residents (56%). Eighty-eight percent (114/129) agreed that "Having a doctor-patient relationship with a resident makes a supervisory relationship more difficult." Significant differences in attitudes were noted between directors who do and do not provide resident medical care. Few directors (10 %) agreed that their residency culture actively encouraged residents to establish doctor-patient relationships with faculty physicians. Only 16 (12%) had created written policies. CONCLUSIONS: It is uncommon for directors to see residents as patients, but most who do feel comfortable with it. Other faculty physicians provide care more frequently. Directors acknowledge potential difficulties with this practice, but few have addressed these issues by creating specific policies. PMID- 26562641 TI - Program Director Participation in a Leadership and Management Skills Fellowship and Characteristics of Program Quality. AB - BACKGROUND AND OBJECTIVES: The association between a residency program director completing a leadership and management skills fellowship and characteristics of quality and innovation of his/her residency program has not been studied. Therefore, the aim of this study is to examine the association between a residency program director's completion of a specific fellowship addressing these skills (National Institute for Program Director Development or NIPDD) and characteristics of quality and innovation of the program they direct. METHODS: Using information from the American Academy of Family Physicians (AAFP), National Resident Matching Program (NRMP) and FREIDA(r) program characteristics were obtained. Descriptive statistics were used to summarize the data. The relationship between programs with a NIPDD graduate as director and program quality measures and indicators of innovation was analyzed using both chi square and logistic regression. RESULTS: Initial analyses showed significant associations between the NIPDD graduate status of a program director and regional location, mean years of program director tenure, and the program's 5-year aggregate ABFM board pass rate from 2007--2011. After grouping the programs into tertiles, the regression model showed significant positive associations with programs offering international experiences and being a NIPDD graduate. CONCLUSIONS: Program director participation in a fellowship addressing leadership and management skills (ie, NIPDD) was found to be associated with higher pass rates of new graduates on a Board certification examination and predictive of programs being in the upper tertile of programs in terms of Board pass rates. PMID- 26562642 TI - STFM Behavioral Science/Family Systems Educator Fellowship: Evaluation of the First 4 Years. AB - BACKGROUND: The discipline of family medicine has long valued the behavioral sciences. Most residency training programs employ a clinical psychologist, social worker, or family therapist to deliver behavioral science curriculum to their residents. However, the cultures and content of training for behavioral sciences and medical professions are quite different, leaving the lone behavioral scientist feeling professionally isolated and unprepared to translate knowledge and skills into tools for the family physician. In response to this need, a group of family medicine educators developed an STFM-sponsored fellowship for behavioral science faculty. The goals of the program were to improve fellows' understanding of the culture of family medicine, provide a curricular toolbox for the behavioral sciences, promote scholarship, and develop a supportive professional network. METHODS: Senior behavioral science faculty at STFM developed a 1-year fellowship program, featuring "classroom learning" at relevant conferences, mentored small-group interactions, and scholarly project requirements. Achievement of program goals was evaluated annually with pre- and post-fellowship surveys. RESULTS: From 2010 to 2014, 59 fellows completed the program; most were psychologists or social workers; two thirds were women. One month after graduation, fellows reported significant increases in understanding the culture of medicine, improved confidence in their curricula and scholarship, and expanded professional networks, compared to pre-fellowship levels. The program required many hours of volunteer time by leaders, faculty, and mentors plus modest support from STFM staff. CONCLUSIONS: Leaders in family medicine education, confronted by the need for inter-professional development, designed and implemented a successful training program for behavioral science faculty. PMID- 26562643 TI - A Medical Student-Driven "Vaccine Blitz" at a School-Based Health Center as an Effective Way to Improve Adolescent Vaccination Rates. AB - BACKGROUND AND OBJECTIVES: Adolescent vaccine rates are below goal in the United States. We sought to assess a medical student driven "vaccine blitz" at a middle school with a school-based health center (SBHC) as a means to increase vaccination. METHODS: Written and/or verbal consent was obtained for specific vaccines needed. Vaccines were given at the SBHC by a team of medical students, public health students, and SBHC staff. Students who received vaccines at the SBHC or primary care physician's (PCP's) office in the 3 weeks after consent was attempted were included as participating in the intervention. RESULTS: Of 184 potential participants, 183 lacked at least one vaccine. On the day of the vaccine blitz, 48 students were given 94 vaccines. During the entire intervention time, an additional 14 students received 38 vaccines at the SBHC, and 23 students received 34 vaccines from their PCP. In sum, 85 students received 166 vaccines from this intervention. Immunization rates increased above the state average for all recommended vaccines; rates of HPV, hepatitis A, and influenza vaccination were most affected. CONCLUSIONS: Medical student-driven vaccine blitzes within an SBHC are a feasible, replicable, and effective way to increase adolescent vaccination rates. In addition, the blitz provided preclinical medical students' exposure to underserved populations, adolescent health as part of the breadth of family medicine, SBHCs, and community medicine and allowed for multidisciplinary work between medical students, public health students, physicians, and nurse practitioners. PMID- 26562644 TI - Socializing Identity Through Practice: A Mixed Methods Approach to Family Medicine Resident Perspectives on Uncertainty. AB - OBJECTIVE: Uncertainty is a central theme in the practice of medicine and particularly primary care. This study explored how family medicine resident physicians react to uncertainty in their practice. METHODS: This study incorporated a two-phase mixed methods approach, including semi-structured personal interviews (n=21) and longitudinal self-report surveys (n=21) with family medicine residents. RESULTS: Qualitative analysis showed that though residents described uncertainty as an implicit part of their identity, they still developed tactics to minimize or manage uncertainty in their practice. Residents described increasing comfort with uncertainty the longer they practiced and anticipated that growth continuing throughout their careers. Quantitative surveys showed that reactions to uncertainty were more positive over time; however, the difference was not statistically significant. DISCUSSION: Qualitative and quantitative results show that as family medicine residents practice medicine their perception of uncertainty changes. To reduce uncertainty, residents use relational information-seeking strategies. From a broader view of practice, residents describe uncertainty neutrally, asserting that uncertainty is simply part of the practice of family medicine. PMID- 26562645 TI - Respiratory Care Training for Safety-Net Primary Care Practices. AB - BACKGROUND AND OBJECTIVES: Programs designed to enhance the diagnosis and management of asthma and chronic obstructive pulmonary disease (COPD) in primary care settings have had variable success and have not been broadly implemented. The Respiratory Toolkit was created to bridge this gap. METHODS: The 2-year program providing primary care training in both asthma and COPD was conducted in an urban federally qualified health center with 13 clinics and 87 staff. The program included interactive training with multidisciplinary teams, in-clinic follow-up trainings, electronic medical record (EMR) tools, and patient-centered educational resources. RESULTS: For asthma patients, use of spirometry increased from 7% of visits before to 43% after training, severity assessment from 13% to 29%, asthma action plans from 2% to 8%, and prescription of inhaled corticosteroids from 33% to 42%. For COPD patients, spirometry use increased from 21% to 35% of visits, and long-acting beta2-agonists from 19% to 26%. Among undiagnosed smokers, use of the COPD screener increased from 0 to 11% of visits, of spirometry from 4% to 36%, and of advice to quit from 74% to 79%. CONCLUSIONS: The Respiratory Toolkit produced significant changes in guideline-based care for patients with asthma or COPD; however, time constraints and other barriers prevented full adoption. PMID- 26562646 TI - Impact of an Interprofessional Teaching Clinic on Preventive Care Services. AB - BACKGROUND AND OBJECTIVES: Recent legislative and regulatory initiatives have emphasized preventive medicine and team-based health care delivery and education. Influenced by these initiatives, the investigators created an interprofessional teaching clinic to provide preventive care services (PCS) structured around Medicare's Annual Wellness Visit (AWV). The primary objective of this pilot study was to determine if PCS status improved for participating patients. METHODS: AWV naive Medicare beneficiaries aged 66--74 years were recruited for the interprofessional teaching clinic, which involved physicians, pharmacists, and nurses. Patients were screened for 11 PCS variables, underwent medication review, and received recommendations to address identified PCS deficiencies prior to completing a satisfaction survey. Follow-up telephone visits were completed to determine recommendation outcomes and final PCS status for each variable. Descriptive statistics were used to characterize patients, the medication review, PCS status, and satisfaction scores. McNemar tests were used to assess the PCS status of patients before and after participation, and Fisher's Exact tests were used to compare baseline PCS status between the pilot cohort and a comparator group. RESULTS: Thirty-four patients were enrolled in the pilot intervention, and one patient was lost to follow-up. Ninety-one percent (10/11) of PCS variables improved following participation. Significant improvements were observed for pneumococcal vaccination, mammography screening, fecal occult blood testing, and bone mineral density scanning. Patient satisfaction was high (mean scores for all items ?4.7). CONCLUSIONS: This interprofessional teaching clinic provides a promising mechanism to improve patients' PCS status, medication utilization, and satisfaction while training students to function effectively as a team. PMID- 26562647 TI - Teams, Gratitude, and Goodbyes. PMID- 26562650 TI - Evidence-Based Medicine Tests. PMID- 26562651 TI - Authors' Reply to "Evidence-Based Medicine Tests". PMID- 26562653 TI - Correction to Electroless Plating of Thin Gold Films Directly onto Silicon Nitride Thin Films and into Micropores. PMID- 26562652 TI - Dynamic Redox Regulation of IL-4 Signaling. AB - Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor initiated oxidation. PMID- 26562654 TI - Correction: Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients. PMID- 26562655 TI - Multiracial Facial Golden Ratio and Evaluation of Facial Appearance. AB - This study aimed to investigate the association of facial proportion and its relation to the golden ratio with the evaluation of facial appearance among Malaysian population. This was a cross-sectional study with 286 randomly selected from Universiti Sains Malaysia (USM) Health Campus students (150 females and 136 males; 100 Malaysian Chinese, 100 Malaysian Malay and 86 Malaysian Indian), with the mean age of 21.54 +/- 1.56 (Age range, 18-25). Facial indices obtained from direct facial measurements were used for the classification of facial shape into short, ideal and long. A validated structured questionnaire was used to assess subjects' evaluation of their own facial appearance. The mean facial indices of Malaysian Indian (MI), Malaysian Chinese (MC) and Malaysian Malay (MM) were 1.59 +/- 0.19, 1.57 +/- 0.25 and 1.54 +/- 0.23 respectively. Only MC showed significant sexual dimorphism in facial index (P = 0.047; P<0.05) but no significant difference was found between races. Out of the 286 subjects, 49 (17.1%) were of ideal facial shape, 156 (54.5%) short and 81 (28.3%) long. The facial evaluation questionnaire showed that MC had the lowest satisfaction with mean score of 2.18 +/- 0.97 for overall impression and 2.15 +/- 1.04 for facial parts, compared to MM and MI, with mean score of 1.80 +/- 0.97 and 1.64 +/- 0.74 respectively for overall impression; 1.75 +/- 0.95 and 1.70 +/- 0.83 respectively for facial parts. IN CONCLUSION: 1) Only 17.1% of Malaysian facial proportion conformed to the golden ratio, with majority of the population having short face (54.5%); 2) Facial index did not depend significantly on races; 3) Significant sexual dimorphism was shown among Malaysian Chinese; 4) All three races are generally satisfied with their own facial appearance; 5) No significant association was found between golden ratio and facial evaluation score among Malaysian population. PMID- 26562656 TI - The effect of the amount of blocking cue training on blocking of appetitive conditioning in mice. AB - Conditioning of a target cue is blocked when it occurs in compound with another cue (blocking cue) that has already received conditioning. Although blocking of appetitive conditioning is commonly used in rodents as a test of selective learning, it has been demonstrated rarely in mice. In order to investigate the conditions that result in blocking in mice two studies tested the effect of the extent of prior blocking cue training on blocking of appetitive conditioning. Mice received either 80 or 200 trials of blocking cue training prior to compound conditioning. A control group received only compound training. Experiment 1 assessed the ability of a visual cue to block conditioning to an auditory target cue. Exposure to the context and the unconditioned stimulus, sucrose pellets, was equated across groups. Blocking was evident in mice that received 200, but not 80 training trials with the visual blocking cue. Responding to the blocking cue was similar across groups. Experiment 2 assessed the ability of an auditory cue to block conditioning to a visual target cue. Blocking was evident in mice trained with 80 and 200 auditory blocking cue trials. The results demonstrate that the strength of blocking in mice is dependent on the modality and experience of the blocking cue. Furthermore, prolonged training of the blocking cue after asymptotic levels of conditioned responding have been reached is necessary for blocking to occur under certain conditions suggesting that the strength of conditioned responding is a limited measure of learning. PMID- 26562657 TI - The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning. AB - The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats. PMID- 26562658 TI - Perceptions of Health Communication, Water Treatment and Sanitation in Artibonite Department, Haiti, March-April 2012. AB - The international response to Haiti's ongoing cholera outbreak has been multifaceted, including health education efforts by community health workers and the distribution of free water treatment products. Artibonite Department was the first region affected by the outbreak. Numerous organizations have been involved in cholera response efforts in Haiti with many focusing on efforts to improve water, sanitation, and hygiene (WASH). Multiple types of water treatment products have been distributed, creating the potential for confusion over correct dosage and water treatment methods. We utilized qualitative methods in Artibonite to determine the population's response to WASH messages, use and acceptability of water treatment products, and water treatment and sanitation knowledge, attitudes and practices at the household level. We conducted eighteen focus group discussions (FGDs): 17 FGDs were held with community members (nine among females, eight among males); one FGD was held with community health workers. Health messages related to WASH were well-retained, with reported improvements in hand washing. Community health workers were identified as valued sources of health information. Most participants noted a paucity of water-treatment products. Sanitation, specifically the construction of latrines, was the most commonly identified need. Lack of funds was the primary reason given for not constructing a latrine. The construction and maintenance of potable water and sanitation services is needed to ensure a sustainable change. PMID- 26562659 TI - The Effects of Hsp90alpha1 Mutations on Myosin Thick Filament Organization. AB - Heat shock protein 90alpha plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90alpha and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90alpha function in myosin thick filament organization. DNA constructs expressing the Hsp90alpha1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90alpha1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90alpha1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90alpha1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90alpha1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90alpha1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90alpha1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation. PMID- 26562660 TI - Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial. AB - OBJECTIVES: To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. DESIGN AND SETTING: A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. PARTICIPANTS: Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. INTERVENTIONS: Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. MAIN OUTCOME MEASURES: Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. RESULTS: At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI 9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. CONCLUSIONS: Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. TRIAL REGISTRATION: ISRCTN registry 33808269. PMID- 26562661 TI - Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening. AB - Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n = 60). The stable and inertial cavitation activities were monitored during sonication. Contrast enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r(2) = 0.77); (2) the permeability of the opened BBB (r(2) = 0.82); (3) the likelihood of safe opening (P < 0.05, safe opening compared to cases of damage; P < 0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r(2) = 0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions. PMID- 26562662 TI - Interleukin (IL)-1beta Is a Strong Inducer of IL-36gamma Expression in Human Colonic Myofibroblasts. AB - BACKGROUNDS AND AIMS: Interleukin (IL)-36 cytokines are members of the IL-1 cytokine family. In this study, we investigated the expression of IL-36gamma in human colonic myofibroblasts to explore the molecular mechanisms underlying IL 36gamma induction. MATERIALS AND METHODS: IL-36 mRNA was analyzed by real-time PCR method. Secretion of IL-36gamma protein was evaluated by Western blot and ELISA analyses. Molecular mechanism of IL-36gamma induction was evaluated by siRNA analyses and immunofluorescence experiments. RESULTS: IL-36gamma mRNA expression was scarcely detected in the cells without stimulation. IL-1beta induced a marked increase of IL-36gamma mRNA expression. TNF-alpha markedly enhanced IL-1beta-induced IL-36gamma mRNA expression. These responses were confirmed at the protein levels. The inhibitors for ERK1/2 (PD98059 and U0216) and a p38 MAPK (SB203580) significantly reduced the IL-1beta-induced IL-36gamma mRNA expression. In addition, the siRNAs specific for NF-kappaB p65 and AP-1 (c Jun) significantly reduced the expression of IL-1beta-induced IL-36gamma mRNA. CONCLUSIONS: Colonic myofibroblasts are cellular source of IL-36gamma in the intestine. IL-36gamma expression was induced by the combination of IL-1beta and TNF-alpha via activation of MAPKs and transcription factors, NF-kappaB and AP-1. PMID- 26562663 TI - Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid. AB - Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7 chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus. PMID- 26562664 TI - Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation. AB - Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior. PMID- 26562665 TI - Intrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis. AB - Parkinson's disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals. Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs). Resume: Here we investigated the long-term effect of the injection of 1ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment. PMID- 26562666 TI - Tolerance to repeated rewarding electrical stimulation of the insular cortex. AB - The insular cortex (IC) has been related to various reinforcing behavioral processes. This study examined the effect of electrical stimulation of the posterior agranular IC on concurrent place preferences. Two groups of animals and their respective controls underwent rewarding brain stimulation every day or on alternate days. While the rats stimulated every other day maintained their preference for the place associated with brain stimulation, those stimulated every day evidenced a reduction in their place preference, suggesting tolerance to the stimulation's rewarding effect. A 15% increase in the current intensity produced a recovery of the preferences of the daily-stimulated rats but had no effect on those stimulated on alternate days. These results are discussed in terms of the rewarding effects induced by different electrical and chemical rewarding agents. PMID- 26562667 TI - Correction: Orally Administrated Lactobacillus pentosus var. plantarum C29 Ameliorates Age-Dependent Colitis by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway via the Regulation of Lipopolysaccharide Production by Gut Microbiota. PMID- 26562669 TI - Association between perfluorinated compound concentrations in cord serum and birth weight using multiple regression models. AB - The effects of exposure to the perfluoroalkyl and polyfluoroalkyl substances (PFASs) perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on birth weight have been examined in several studies, but other PFASs have not been considered. We conducted a cross-sectional survey of newborns in Seoul, South Korea, collecting 118 serum samples, for 85 of which we had a full range of information. We conducted multiple regression analyses to examine the association between nine PFAS concentrations in cord serum and birth weight. Seven PFASs were found in cord serum, PFOA and PFOS being dominant, with mean concentrations of 1.11 and 0.87ng/mL, respectively. The adjusted birth weight changes (natural log) were -0.14 (95% confidence interval -0.33-0.03) for PFOS and -0.03 (95% confidence interval -0.25-0.18) for PFOA. None of the PFASs were statistically associated with birth weight in this population. PMID- 26562668 TI - Strain Interactions as a Mechanism for Dominant Strain Alternation and Incidence Oscillation in Infectious Diseases: Seasonal Influenza as a Case Study. AB - BACKGROUND: Many human infectious diseases are caused by pathogens that have multiple strains and show oscillation in infection incidence and alternation of dominant strains which together are referred to as epidemic cycling. Understanding the underlying mechanisms of epidemic cycling is essential for forecasting outbreaks of epidemics and therefore important for public health planning. Current theoretical effort is mainly focused on the factors that are extrinsic to the pathogens themselves ("extrinsic factors") such as environmental variation and seasonal change in human behaviours and susceptibility. Nevertheless, co-circulation of different strains of a pathogen was usually observed and thus strains interact with one another within concurrent infection and during sequential infection. The existence of these intrinsic factors is common and may be involved in the generation of epidemic cycling of multi-strain pathogens. METHODS AND FINDINGS: To explore the mechanisms that are intrinsic to the pathogens themselves ("intrinsic factors") for epidemic cycling, we consider a multi-strain SIRS model including cross-immunity and infectivity enhancement and use seasonal influenza as an example to parameterize the model. The Kullback Leibler information distance was calculated to measure the match between the model outputs and the typical features of seasonal flu (an outbreak duration of 11 weeks and an annual attack rate of 15%). Results show that interactions among strains can generate seasonal influenza with these characteristic features, provided that: the infectivity of a single strain within concurrent infection is enhanced 2-7 times that within a single infection; cross-immunity as a result of past infection is 0.5-0.8 and lasts 2-9 years; while other parameters are within their widely accepted ranges (such as a 2-3 day infectious period and the basic reproductive number of 1.8-3.0). Moreover, the observed alternation of the dominant strain among epidemics emerges naturally from the best fit model. Alternative modelling that also includes seasonal forcing in transmissibility shows that both external mechanisms (i.e. seasonal forcing) and the intrinsic mechanisms (i.e., strain interactions) are equally able to generate the observed time-series in seasonal flu. CONCLUSIONS: The intrinsic mechanism of strain interactions alone can generate the observed patterns of seasonal flu epidemics, but according to Kullback-Leibler information distance the importance of extrinsic mechanisms cannot be excluded. The intrinsic mechanism illustrated here to explain seasonal flu may also apply to other infectious diseases caused by polymorphic pathogens. PMID- 26562670 TI - Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. AB - BACKGROUND: Patients with pituitary stalk interruption syndrome (PSIS) are initially referred for hypoglycemia during the neonatal period or growth retardation during childhood. PSIS is either isolated (nonsyndromic) or associated with extra-pituitary malformations (syndromic). OBJECTIVE: To compare baseline characteristics and long-term evolution in patients with PSIS according to the initial presentation. STUDY DESIGN: Sixty-seven patients with PSIS were included. Data from subgroups were compared: neonates (n = 10) versus growth retardation patients (n = 47), and syndromic (n = 32) versus nonsyndromic patients (n = 35). RESULTS: Neonates displayed a more severe hormonal and radiological phenotype than children referred for growth retardation, with a higher incidence of multiple hormonal deficiencies (100% versus 34%; P = 0.0005) and a nonvisible anterior pituitary lobe (33% versus 2%; P = 0.0017). Regular follow-up of growth might have allowed earlier diagnosis in the children with growth retardation, as decreased growth velocity and growth retardation were present respectively 3 and 2 years before referral. We documented a progressive worsening of endocrine impairment throughout childhood in these patients. Presence of extra-pituitary malformations (found in 48%) was not associated with more severe hormonal and radiological characteristics. Growth under GH treatment was similar in the patient groups and did not vary according to the pituitary MRI findings. CONCLUSIONS: PSIS diagnosed in the neonatal period has a particularly severe hormonal and radiological phenotype. The progressive worsening of endocrine impairment throughout childhood justifies periodic follow-up to check for additional hormonal deficiencies. PMID- 26562672 TI - Preliminary research developing a theory of cell phone distraction and social relationships. AB - Motor vehicle crashes remain the leading cause of death and injury for people aged 5-34, accounting annually for over 3000 deaths, and 100 times as many injuries. It is well established that distracted driving, and cell phone use while driving in particular, pose significant crash risk to drivers. Research has demonstrated that drivers are well aware of this danger but over 90% of drivers report using a cell phone while driving. Given the likely role that social influence plays in how people use cell phones while driving surprisingly little research has been conducted investigating to whom drivers are talking or texting. We report the results of a national survey to determine who drivers are most likely to call or text when behind the wheel and compared these results with general cell phone calling and texting patterns as well as previous findings on the prevalence of calling and texting while driving. The results suggest that social distance is a key factor in cell phone use while driving: Teens are more likely to talk with parents, and adults are more likely to talk with spouses than general calling patterns would suggest. We discuss whether the purpose of calls made while driving, such as coordination, could help explain these patterns. We propose next steps for further examining the role social relationships play in cell phone use while driving to potentially reduce teen driver cell phone use by lowering the number of calls from parents. PMID- 26562671 TI - Ebolavirus Evolution: Past and Present. AB - The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been around for almost 50 years. In this review, we discuss past and present outbreaks of EBOV and how those variants evolved over time. We explore and discuss selective pressures that drive the evolution of different Ebola variants, and how they may modify the efficacy of therapeutic treatments and vaccines currently being developed. Finally, given the unprecedented size and spread of the outbreak, as well as the extended period of replication in human hosts, specific attention is given to the 2014-2015 West African outbreak variant (Makona). PMID- 26562673 TI - Are signalized intersections with cycle tracks safer? A case-control study based on automated surrogate safety analysis using video data. AB - Cities in North America have been building bicycle infrastructure, in particular cycle tracks, with the intention of promoting urban cycling and improving cyclist safety. These facilities have been built and expanded but very little research has been done to investigate the safety impacts of cycle tracks, in particular at intersections, where cyclists interact with turning motor-vehicles. Some safety research has looked at injury data and most have reached the conclusion that cycle tracks have positive effects of cyclist safety. The objective of this work is to investigate the safety effects of cycle tracks at signalized intersections using a case-control study. For this purpose, a video-based method is proposed for analyzing the post-encroachment time as a surrogate measure of the severity of the interactions between cyclists and turning vehicles travelling in the same direction. Using the city of Montreal as the case study, a sample of intersections with and without cycle tracks on the right and left sides of the road were carefully selected accounting for intersection geometry and traffic volumes. More than 90h of video were collected from 23 intersections and processed to obtain cyclist and motor-vehicle trajectories and interactions. After cyclist and motor-vehicle interactions were defined, ordered logit models with random effects were developed to evaluate the safety effects of cycle tracks at intersections. Based on the extracted data from the recorded videos, it was found that intersection approaches with cycle tracks on the right are safer than intersection approaches with no cycle track. However, intersections with cycle tracks on the left compared to no cycle tracks seem to be significantly safer. Results also identify that the likelihood of a cyclist being involved in a dangerous interaction increases with increasing turning vehicle flow and decreases as the size of the cyclist group arriving at the intersection increases. The results highlight the important role of cycle tracks and the factors that increase or decrease cyclist safety. Results need however to be confirmed using longer periods of video data. PMID- 26562674 TI - Hadrosauroid Dinosaurs from the Late Cretaceous of the Sultanate of Oman. AB - Fragmentary post-cranial remains (femora, tibia, vertebrae) of ornithischian dinosaurs from the Late Cretaceous of the Sultanate of Oman are described and referred to hadrosauroids. The specimens come from the Al-Khod Conglomerate, of latest Campanian to Maastrichtian age, in the north-eastern part of the country. Although the fragmentary condition of the fossils precludes a precise identification, various characters, including the shape of the fourth trochanter of the femur and the morphology of its distal end, support an attribution to hadrosauroids. With the possible exception of a possible phalanx from Angola, this group of ornithopod dinosaurs, which apparently originated in Laurasia, was hitherto unreported from the Afro-Arabian plate. From a paleobiogeographical point of view, the presence of hadrosauroids in Oman in all likelihood is a result of trans-Tethys dispersal from Asia or Europe, probably by way of islands in the Tethys shown on all recent paleogeographical maps of that area. Whether hadrosauroids were widespread on the Afro-Arabian landmass in the latest Cretaceous, or where restricted to the " Oman island " shown on some paleogeographical maps, remains to be determined. PMID- 26562675 TI - The defence elicitor AsES causes a rapid and transient membrane depolarization, a triphasic oxidative burst and the accumulation of nitric oxide. AB - The newly characterized elicitor AsES obtained from Acremonium strictum induces a strong defence response in strawberry plants and confers plants resistance against the fungal pathogen Colletotricum acutatum the casual agent of anthracnose disease. Previous studies showed that AsES causes the accumulation of reactive oxygen species (ROS) that peaked 4 h post treatment (hpt), but due to the experimental approach used it was not clear whether the accumulation of ROS observed was intracellular or extracellular or took place as a single peak. By using a different experimental setup, a more complex early events associated to the activation of the innate immunity were observed. In this paper we report that strawberry plant cells treated with AsES exhibits a triphasic production of H2O2 and a rapid intracellular accumulation of NO. The first phase consists in a progressive extracellular accumulation of H2O2 that starts immediately after the treatment with AsES and is preceded by a rapid and transient cell membrane depolarization. During this phase takes place also a rapid intracellular accumulation of NO. Microscopic observations of mesophyll cells treated with AsES reveals that NO accumulates at the chloroplast. After the first extracellular H2O2 production phase, two intracellular H2O2 accumulation events occur, the first 2 hpt, and the second 7 hpt. Cells treated with AsES also show a transient increase of ion leakage, and a progressive alkalinization of the extracellular medium. PMID- 26562676 TI - A Keystone Ant Species Provides Robust Biological Control of the Coffee Berry Borer Under Varying Pest Densities. AB - Species' functional traits are an important part of the ecological complexity that determines the provisioning of ecosystem services. In biological pest control, predator response to pest density variation is a dynamic trait that impacts the provision of this service in agroecosystems. When pest populations fluctuate, farmers relying on biocontrol services need to know how natural enemies respond to these changes. Here we test the effect of variation in coffee berry borer (CBB) density on the biocontrol efficiency of a keystone ant species (Azteca sericeasur) in a coffee agroecosystem. We performed exclosure experiments to measure the infestation rate of CBB released on coffee branches in the presence and absence of ants at four different CBB density levels. We measured infestation rate as the number of CBB bored into fruits after 24 hours, quantified biocontrol efficiency (BCE) as the proportion of infesting CBB removed by ants, and estimated functional response from ant attack rates, measured as the difference in CBB infestation between branches. Infestation rates of CBB on branches with ants were significantly lower (71%-82%) than on those without ants across all density levels. Additionally, biocontrol efficiency was generally high and did not significantly vary across pest density treatments. Furthermore, ant attack rates increased linearly with increasing CBB density, suggesting a Type I functional response. These results demonstrate that ants can provide robust biological control of CBB, despite variation in pest density, and that the response of predators to pest density variation is an important factor in the provision of biocontrol services. Considering how natural enemies respond to changes in pest densities will allow for more accurate biocontrol predictions and better-informed management of this ecosystem service in agroecosystems. PMID- 26562677 TI - The indirect effect of emotion dysregulation in terms of negative affect and smoking-related cognitive processes. AB - INTRODUCTION: Although negative affect is associated with a number of smoking related cognitive processes, the mechanisms underlying these associations have yet to be examined. The current study sought to examine the indirect effect of emotion regulation difficulties in terms of the association between negative affect and smoking-related cognitive processes (internal barriers to cessation, negative affect reduction smoking motives, negative affect reduction smoking outcome expectancies). METHOD: Participants were 126 daily cigarette smokers (70.4% male, Mage=36.5years, SD=13.0; 69.8% Caucasian) who smoked an average of 18.5 (SD=8.7) cigarettes per day and reported moderate nicotine dependence. RESULTS: Formal mediation analyses were conducted using PROCESS to examine the indirect effect of negative affect on internal barriers to cessation and negative affect reduction smoking motives and outcome expectancies through emotion regulation difficulties. After accounting for the effects of gender, daily smoking rate, and anxiety sensitivity, negative affect was indirectly related to internal barriers to cessation and negative affect reduction smoking motives through emotion regulation difficulties. There was no significant indirect effect for negative affect reduction smoking outcome expectancies. CONCLUSIONS: These findings suggest that greater negative affect is associated with a desire to smoke to reduce this negative affect and perceptions that quitting smoking will be difficult due to negative emotions because of greater difficulties managing these negative emotions. Thus, emotion regulation difficulties may be an important target for smoking cessation interventions. PMID- 26562678 TI - The evolution of Internet addiction: A global perspective. AB - Kimberly Young's initial work on Internet addiction (IA) was pioneering and her early writings on the topic inspired many others to carry out research in the area. Young's (2015) recent paper on the 'evolution of Internet addiction' featured very little European research, and did not consider the main international evidence that has contributed to our current knowledge about the conceptualization, epidemiology, etiology, and course of Internet-related disorders. This short commentary paper elaborates on important literature omitted by Young that the present authors believe may be of use to researchers. We also address statements made in Young's (2015) commentary that are incorrect (and therefore misleading) and not systematically substantiated by empirical evidence. PMID- 26562679 TI - The relationship between general causality orientation and treatment outcome among marijuana-dependent adults. AB - General causality orientations are motivational styles that are indicative of a person's belief about personal change and their motivation to change. The purpose of the current study was to investigate whether causality orientations were associated with marijuana treatment outcomes in a sample of marijuana-dependent individuals. A total of 74 participants (66% male) were recruited from the Seattle, Washington area and randomly assigned to receive a combination of motivational enhancement and cognitive behavioral therapy or the combination treatment plus additional "check-up" sessions. Follow-up assessments evaluated frequency of use, use-related problems, and marijuana use disorder symptoms through 9months. Causality orientations were relatively stable over time. Posttreatment Autonomy orientations were associated with lower frequency of use and Controlled orientations were associated with a reduction in use, problems, and marijuana use disorder symptoms. Autonomy and Controlled orientations were associated with readiness to change. Results suggest that both autonomous and controlled orientations have implications for response to treatment; perhaps for different reasons. Causality orientations may be a promising avenue of research to predict treatment response and outcome. PMID- 26562680 TI - Social cohesion and the smoking behaviors of adults living with children. AB - INTRODUCTION: The smoking behavior of adults can negatively impact children through exposure to environmental tobacco smoke and by modeling this unhealthy behavior. Little research has examined the role of the social environment in smoking behaviors of adults living with children. The present study specifically analyzed the relationship between social cohesion and smoking behaviors of adults living with children. METHODS: Data from the 2009 California Health Interview Survey, a random-digit dial cross-sectional survey of California Adults, were used. Adults living with children reported their levels of social cohesion and smoking behaviors (N=13,978). Logistic regression models were used to predict odds of being a current smoker or living in a household in which smoking was allowed, from social cohesion. RESULTS: Overall, 13% of the sample was current smokers and 3.74% lived in households in which smoking was allowed. Logistic regression models showed that each one-unit increase in social cohesion is associated with reduced odds of being a current smoker (AOR=0.92; 95% CI=0.85 0.99) and reduced odds of living in a household in which smoking is allowed (AOR=0.84; 95% CI=0.75-0.93), after controlling for sociodemographic characteristics. CONCLUSIONS: Among adults living with children, higher social cohesion is associated with a lower likelihood of both being and smoker and living in a home where smoking is allowed. Thus, future research is needed to better understand mechanisms that explain the relationship between social cohesion and smoking-related behavior in order to prevent smoking-related health consequences and smoking initiation among children and adults. PMID- 26562681 TI - Cognition-related brain networks underpin the symptoms of unipolar depression: Evidence from a systematic review. AB - This systematic review sources the latest neuroimaging evidence for the role of cognition-related brain networks in depression, and relates their abnormal functioning to symptoms of the disorder. Using theoretically informed and rigorous inclusion criteria, we integrate findings from 59 functional neuroimaging studies of adults with unipolar depression using a narrative approach. Results demonstrate that two distinct neurocognitive networks, the autobiographic memory network (AMN) and the cognitive control network (CCN), are central to the symptomatology of depression. Specifically, hyperactivity of the introspective AMN is linked to pathological brooding, self-blame, rumination. Anticorrelated under-engagement of the CCN is associated with indecisiveness, negative automatic thoughts, poor concentration, distorted cognitive processing. Downstream effects of this imbalance include reduced regulation of networks linked to the vegetative and affective symptoms of depression. The configurations of these networks can change between individuals and over time, plausibly accounting for both the variable presentation of depressive disorders and their fluctuating course. Framing depression as a disorder of neurocognitive networks directly links neurobiology to psychiatric practice, aiding researchers and clinicians alike. PMID- 26562682 TI - Molecular regulation of dendritic spine dynamics and their potential impact on synaptic plasticity and neurological diseases. AB - The structure and dynamics of dendritic spines reflect the strength of synapses, which are severely affected in different brain diseases. Therefore, understanding the ultra-structure, molecular signaling mechanism(s) regulating dendritic spine dynamics is crucial. Although, since last century, dynamics of spine have been explored by several investigators in different neurological diseases, but despite countless efforts, a comprehensive understanding of the fundamental etiology and molecular signaling pathways involved in spine pathology is lacking. The purpose of this review is to provide a contextual framework of our current understanding of the molecular mechanisms of dendritic spine signaling, as well as their potential impact on different neurodegenerative and psychiatric diseases, as a format for highlighting some commonalities in function, as well as providing a format for new insights and perspectives into this critical area of research. Additionally, the potential strategies to restore spine structure-function in different diseases are also pointed out. Overall, these informations should help researchers to design new drugs to restore the structure-function of dendritic spine, a "hot site" of synaptic plasticity. PMID- 26562683 TI - Correlation between Clinical, Placental Histology and Microbiological Findings in Spontaneous Preterm Births. AB - AIMS: To examine the occurrence of chorioamnionitis and abruption among women who had a spontaneous preterm birth (SPTB), the correlation between clinical and placental findings, and the impact of these complications on neonatal outcome after delivery. METHODS: This was a retrospective case-control study conducted between 2008 and 2012 at a single teaching hospital. The study group included all women who had an SPTB (23-36 weeks). Placentas were cultured and underwent histological examination. RESULTS: A total of 478 women were included. The mean gestational age at delivery was 32.6 +/- 3.1 weeks. Overall, 260 (54.4%) women had either clinical and/or histological abruption or chorioamnionitis. Clinical chorioamnionitis was diagnosed before birth in 14 (2.9%) women, while histological chorioamnionitis (HCA) in 84 (17.4%). Overall, 38 neonates had infection. Placental cultures were negative in 65.8% (25/38) of these neonates, and in 77.1% (27/38), HCA was ruled out. Logistic regression analysis revealed that neonatal morbidity and mortality were correlated with gestational age at delivery (p = 0.02), not with placental pathology (p = 0.08). CONCLUSIONS: Half of the women with PTB had clinical or histological abruption, chorioamnionitis or both. A partial correlation was found between clinical and placental findings. The main determinant of neonatal outcome was gestational age at delivery and not placental findings. PMID- 26562684 TI - Co-delivery of doxorubicin and (131)I by thermosensitive micellar-hydrogel for enhanced in situ synergetic chemoradiotherapy. AB - Combined chemoradiotherapy is potent to defeat malignant tumor. Concurrent delivery of radioisotope with chemotherapeutic drugs, which also act as the radiosensitizer, to tumor tissues by a single vehicle is essential to achieve this objective. To this end, a macroscale injectable and thermosensitive micellar hydrogel (MHg) depot was constructed by thermo-induced self-aggregation of poly(epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) poly(ethyleneglycol)-poly(epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9 undecanone) (PECT) triblock copolymer micelles (Ms), which could not only serve as a micellar drug reservoir to locally deliver concentrated nano chemotherapeutic drugs, but also immobilize radioisotopes at the internal irradiation hot focus. Doxorubicin (DOX) and iodine-131 labeled hyaluronic acid ((131)I-HA) were used as the model therapeutic agents. The aqueous mixture of drug-loaded PECT micelles and (131)I-HA exhibited sol-to-gel transition around body temperature. In vitro drug release study indicated that PECT/DOX Ms were sustainedly shed from the native PECT/DOX MHg formulation, which could be internalized by tumor cells with rapid intracellular DOX release. This hydrogel formulation demonstrated considerable in vitro antitumor effect as well as remarkable radiosensitization. In vivo subcutaneous injection of PECT MHg demonstrated that (131)I isotope was immobilized stably at the injection location and no obvious indication of damage to major organs were observed as indicated by the histopathological analysis. Furthermore, the peritumoral injection of chemo radiation therapeutic agents-encapsulated MHg formulation on tumor-bearing nude mice resulted in the desired combined treatment effect, which significantly improved the tumor growth inhibition efficiency with minimized drug-associated side effects to major organs. Consequently, such a thermosensitive MHg formulation, which enabled the precise control over the dosage and ratio of combination therapeutic agents to obtain the desired therapeutic effect with a single drug administration and reduced side effects, holds great potential for spatiotemporally delivery of multiple bioactive agents for sustained combination therapy. PMID- 26562685 TI - Immunization with antigenic peptides complexed with beta-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs. AB - The induction of antigen-specific immune responses requires immunization with not only antigens, but also adjuvants. CpG oligonucleotides (CpG-ODNs) are well-known ligands for Toll-like receptor 9 and a potent adjuvant that induces both Th1-type humoral and cellular immune responses including cytotoxic T-lymphocyte responses. We previously demonstrated that beta-glucan schizophyllan (SPG) can form complexes with CpG-ODNs with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses by co-administration of antigenic proteins, namely ovalbumin (OVA). Immunization with antigenic peptides, OVA257-264, did not induce these antigen specific immune responses even in combination with CpG-dA/SPG, indicating that peptides require a carrier to antigen presenting cells. In this study, we prepared conjugates comprising OVA257-264 and dA40, and made complexes with SPG. Immunization with OVA257-264-dA/SPG induced peptide-specific immune responses in combination with CpG-dA regardless of complexation with SPG both in vitro and in vivo. When splenocytes from immunized mice were incubated with E.G7-OVA tumor model cells presenting OVA peptides, the number of cells drastically decreased after 24h. Furthermore, mice pre-immunized with OVA257-264-dA/SPG and CpG-ODNs exhibited a long delay in tumor growth after tumor inoculation. Therefore, these peptide-dA/SPG and CpG-dA/SPG complexes could be used as a potent vaccine for the treatment of cancers and infectious diseases. PMID- 26562686 TI - Episodic future thinking reduces eating in a food court. AB - Episodic future thinking (EFT) is the psychological process of vividly imagining a future event, and this process has been shown to reduce overeating in the laboratory. To assess the efficacy of EFT in the natural environment, twenty-nine overweight or obese women who wanted to improve their eating habits were randomly assigned to one of two smartphone-implemented interventions--EFT or control episodic recent thinking (ERT)--while they ate dinner in a public food court. Results showed a reduction in consumption of total calories, a reduction in percent calories from fat, and an increase in percent calories from protein for EFT versus ERT. These data suggest EFT may be used to modify eating habits in natural eating environments, and may show potential as a component of behavioral obesity interventions. PMID- 26562687 TI - Acetone-butanol-ethanol production from Kraft paper mill sludge by simultaneous saccharification and fermentation. AB - Paper mill sludge (PS), a solid waste from pulp and paper industry, was investigated as a feedstock for acetone-butanol-ethanol (ABE) production by simultaneous saccharification and fermentation (SSF). ABE fermentation of paper sludge by Clostridium acetobutylicum required partial removal of ash in PS to enhance its enzymatic digestibility. Enzymatic hydrolysis was found to be a rate limiting step in the SSF. A total of 16.4-18.0g/L of ABE solvents were produced in the SSF of de-ashed PS with solid loading of 6.3-7.4% and enzyme loading of 10 15FPU/g-glucan, and the final solvent yield reached 0.27g/g sugars. No pretreatment and pH control were needed in ABE fermentation of paper sludge, which makes it an attractive feedstock for butanol production. The results suggested utilization of paper sludge should not only consider the benefits of buffering effect of CaCO3 in fermentation, but also take into account its inhibitory effect on enzymatic hydrolysis. PMID- 26562688 TI - A new activated primary tank developed for recovering carbon source and its application. AB - A novel activated primary tank process (APT) was developed for recovering carbon source by fermentation and elutriation of primary sludge. The effects of solids retention time (SRT), elutriation intensity (G) and return sludge ratio (RSR) on this recovery were evaluated in a pilot scale reactor. Results indicated that SRT significantly influenced carbon source recovery, and mechanical elutriation could promote soluble COD (SCOD) and VFA yields. The optimal conditions of APT were SRT=5d, G=152s(-1) and RSR=10%, SCOD and VFA production were 57.0mg/L and 21.7mg/L. Particulate organic matter in sludge was converted into SCOD and VFAs as fermentative bacteria were significantly enriched in APT. Moreover, the APT process was applied in a wastewater treatment plant to solve the problem of insufficient carbon source. The outcomes demonstrated that influent SCOD of biological tank increased by 31.1%, which improved the efficiency of removing nitrogen and phosphorus. PMID- 26562689 TI - A simple kinetic analysis of syngas during steam hydrogasification of biomass using a novel inverted batch reactor with instant high pressure feeding. AB - A newly designed inverted batch reactor equipped with a pressure-driven feeding system was built for investigating the kinetics of syngas during the steam hydrogasification (SHR) of biomass. The system could instantly load the feedstock into the reactor at high temperature and pressure, which simulated the way to transport the feedstock into a hot and pressurized gasifier. Experiments were conducted from 600 degrees C to 700 degrees C. The inverted reactor showed very high heating rate by enhancing the carbon conversion and syngas production. The kinetic study showed that the rates of CH4, CO and CO2 formation during SHR were increased when the gasification temperature went up. SHR had comparatively lower activation energy for CH4 production. The activation energies of CH4, CO and CO2 during SHR were 42.8, 51.8 and 14kJ/mol, respectively. PMID- 26562690 TI - Effects of cytoplasm and reactant polarities on acid-catalyzed lipid transesterification in wet microalgal cells subjected to microwave irradiation. AB - The polarities of the cytoplasm and reactants were measured through dielectric spectroscopy, contact angle test, NMR, and FTIR to investigate the mechanisms underlying acid-catalyzed lipid transesterification in wet microalgal cells subjected to microwave irradiation. Organics with apolar functional groups in the cytoplasm decreased the contact angle of methanol against triglyceride by 13.92 degrees , which subsequently increased transesterification efficiency by 2.4 times. The microalgal biomass, given its higher hydrophilicity index of 1.96 than lipids, was more accessible to hydrophilic alcohols, which subsequently promoted transesterification. Water in the cytoplasm promoted the dielectric constant of methanol and increased the contact angle of methanol against triglyceride by 20.51 degrees , which subsequently decreased transesterification efficiency by 72.6%. The inhibitory effect of water on transesterification weakened with the prolonged carbon lengths of the alcohols because of decreased polarity. Microwave decreased the electric constants of alcohols and reduced the polarity difference between alcohols and lipids, thereby improving transesterification efficiency. PMID- 26562691 TI - Molecular Characterization of Plasmids Encoding CTX-M beta-Lactamases and their Associated Addiction Systems Circulating Among Escherichia coli from Retail Chickens, Chicken Farms, and Slaughterhouses in Korea. AB - Extended-spectrum beta-lactamases (ESBLs), particularly those of the CTX-M types, are the predominant resistance determinants of Escherichia coli that are rapidly spreading worldwide. To determine CTX-M types, E. coli isolates were collected from retail chickens (n = 390) and environmental samples from chicken farms (n = 32) and slaughterhouses (n = 67) in Korea. Fifteen strains harboring blaCTX-M genes were isolated from 358 E. coli isolates. The most common CTX-M type was eight of CTX-M-15, followed by six of CTX-M-1 and one of CTX-M- 14. The blaCTX-M genes were identified in the isolates from retail chickens (n = 9), followed by feces, water pipes, floors, and walls. Conjugations confirmed the transferability of the plasmids carrying blaCTX-M genes to the recipient E. coli J53 strain. Furthermore, eight addiction systems carried by the replicons in CTX-M types were confirmed. The dominant system was identified as ccdAB, vagCD, and pndAC in donor strains and transconjugants. The clonal relationship between the two strains carrying blaCTX-M genes indicates that E. coli may transmit from the farm to retail chickens, suggesting a possible public health risk. Our findings demonstrate that the detection of CTX-M types in E. coli isolates is important for tracking ESBL production in animals, and suggest linkage of multiple addiction systems in plasmids bearing blaCTX-M genes. PMID- 26562692 TI - Phage Conversion for beta-Lactam Antibiotic Resistance of Staphylococcus aureus from Foods. AB - Temperate phages have been suggested to carry virulence factors and other lysogenic conversion genes that play important roles in pathogenicity. In this study, phage TEM123 in wild-type Staphylococcus aureus from food sources was analyzed with respect to its morphology, genome sequence, and antibiotic resistance conversion ability. Phage TEM123 from a mitomycin C-induced lysate of S. aureus was isolated from foods. Morphological analysis under a transmission electron microscope revealed that it belonged to the family Siphoviridae. The genome of phage TEM123 consisted of a double-stranded DNA of 43,786 bp with a G+C content of 34.06%. A bioinformatics analysis of the phage genome identified 43 putative open reading frames (ORFs). ORF1 encoded a protein that was nearly identical to the metallo-beta-lactamase enzymes that degrade beta-lactam antibiotics. After transduction to S. aureus with phage TEM123, the metallo-beta lactamase gene was confirmed in the transductant by PCR and sequencing analyses. In a beta-lactam antibiotic susceptibility test, the transductant was more highly resistant to beta-lactam antibiotics than S. aureus S133. Phage TEM123 might play a role in the transfer of beta-lactam antibiotic resistance determinants in S. aureus. Therefore, we suggest that the prophage of S. aureus with its exotoxin is a risk factor for food safety in the food chain through lateral gene transfer. PMID- 26562693 TI - Overproduction of the Escherichia coli Chaperones GroEL-GroES in Rhodococcus ruber Improves the Activity and Stability of Cell Catalysts Harboring a Nitrile Hydratase. AB - Three combinations of molecular chaperones from Escherichia coli (i.e., DnaK-DnaJ GrpEGroEL- GroES, GroEL-GroES, and DnaK-DnaJ-GrpE) were overproduced in E. coli BL21, and their in vitro stabilizing effects on a nitrile hydratase (NHase) were assessed. The optimal gene combination, E. coli groEL-groES (ecgroEL-ES), was introduced into Rhodococcus ruber TH3. A novel engineered strain, R. ruber TH3G was constructed with the native NHase gene on its chromosome and the heterologous ecgroEL-ES genes in a shuttle plasmid. In R. ruber TH3G, NHase activity was enhanced 37.3% compared with the control, TH3. The in vivo stabilizing effect of ecGroEL-ES on the NHase was assessed using both acrylamide immersion and heat shock experiments. The inactivation behavior of the in vivo NHase after immersion in a solution of dynamically increased concentrations of acrylamide was particularly evident. When the acrylamide concentration was increased to 500 g/l (50%), the remaining NHase activity in TH3G was 38%, but in TH3, activity was reduced to 10%. Reactivation of the in vivo NHases after varying degrees of inactivation was further assessed. The activity of the reactivated NHase was more than 2-fold greater in TH3G than in TH3. The hydration synthesis of acrylamide catalyzed by the in vivo NHase was performed with continuous acrylonitrile feeding. The final concentration of acrylamide was 640 g/l when catalyzed by TH3G, compared with 490 g/l acrylamide by TH3. This study is the first to show that the chaperones ecGroEL-ES work well in Rhodococcus and simultaneously possess protein-folding assistance functions and the ability to stabilize and reactivate the native NHases. PMID- 26562694 TI - Trends in Male and Female Genital Warts Among Adolescents in a Safety-Net Health Care System 2004-2013: Correlation With Introduction of Female and Male Human Papillomavirus Vaccination. AB - BACKGROUND: Human papillomavirus (HPV) vaccination remains underused in the United States, and few population-level studies on effectiveness exist. METHODS: We examined trends in rates of genital warts diagnoses and HPV vaccination rates (defined as receipt of 1 or more vaccine doses) among low-income and minority adolescents between 2004 and 2013. Data were obtained from a database containing de-identified medical record information including all outpatient visits to an urban medical center and 6 affiliated community health centers. International Classification of Diseases, Ninth Revision codes were used to determine genital warts diagnoses. We estimated annual rates of genital warts for each period for females and males using an interrupted time-series Poisson regression model. RESULTS: As HPV vaccination rates in low-income, minority adolescents rose from 0% to 59% (females) and 0 to 41% (males) between 2004 and 2013, genital warts rates decreased from 3.5% (females) and 3.6% (males) to 1.5% (females) and 2.9% (males). Rates of genital warts decreased significantly for both females and males from the prevaccination to the postvaccination periods (P < 0.05 for both comparisons). Genital warts rates for males began to decrease after the introduction of female vaccination and continued to decrease after male vaccination was introduced. CONCLUSIONS: Introduction of HPV vaccination correlated with lower rates of genital warts among a cohort of low-income and minority adolescents. Rates of genital warts began to decrease in females and males following the introduction of female vaccination and continued to fall after the introduction of male vaccination, indicating that male vaccination may confer additional benefit to both males and females over herd immunity alone, especially when vaccination rates are suboptimal. PMID- 26562695 TI - Prevalence of Anal Human Papillomavirus Vaccine Types in the Bangkok Men Who Have Sex With Men Cohort Study. AB - BACKGROUND: The quadrivalent human papillomavirus (qHPV) and 9 valent (nHPV) vaccine are licensed for males to prevent anal HPV-associated dysplasia and cancer caused by HPV types 6, 11, 16, and 18 (qHPV) and additional types 33, 35, 45, 52, and 58 (nHPV), respectively. Both conditions are common in HIV-infected and HIV-uninfected men who have sex with men (MSM). It is not well documented which anal HPV vaccine types are most prevalent in Southeast Asia. METHODS: A convenience sample of 400 anal swabs were obtained from 200 HIV-infected and 200 HIV-uninfected sexually active Bangkok MSM Cohort Study participants. After swab collection in PreservCyt (Cytyc Corp, Marlborough, MA), the media was stored at 80 degrees C until processing. DNA was extracted, amplified by polymerase chain reaction, denatured, and then hybridized to probes for 37 HPV types and beta globin. RESULTS: The mean participant age was 25.6 years (range, 18-55 years); the mean CD4 T-cell count was 410 cells/mm in the HIV-infected participants. Among all swab samples, 386 (192 HIV-positive and 194 HIV-negative) had adequate beta-globin for HPV genotype testing. Anal HPV type was detected in 44.3% of participants whose samples underwent genotype testing. Both qHPV and nHPV types were more frequently detected in HIV-infected compared with HIV-uninfected (42.2% vs. 23.2% [P < 0.01], 50.0% vs. 24.2% [P < 0.01]), respectively). There were no significant relationships between social behaviors (alcohol use, drug use) or sexual behaviors (number of partners, condom usage, sexual positioning) and anal HPV prevalence. CONCLUSIONS: The prevalence of anal vaccine HPV types in Thai MSM was similar to that reported in MSM from Western populations and has a similar distribution by HIV status. Targeting young MSM with vaccination could offer protection against HPV vaccine types. PMID- 26562696 TI - Epidemiology of Human Papillomavirus Detected in the Oral Cavity and Fingernails of Mid-Adult Women. AB - BACKGROUND: Oral and fingernail human papillomavirus (HPV) detection may be associated with HPV-related carcinoma risk at these nongenital sites and foster transmission to the genitals. We describe the epidemiology of oral and fingernail HPV among mid-adult women. METHODS: Between 2011 and 2012, 409 women aged 30 to 50 years were followed up for 6 months. Women completed health and behavior surveys and provided self-collected oral, fingernail, and vaginal specimens at enrollment and exit for type-specific HPV DNA testing. Concordance of type specific HPV detection across anatomical sites was described with kappa statistics. Using generalized estimating equations or exact logistic regression, we measured the univariate associations of various risk factors with type specific oral and fingernail HPV detection. RESULTS: Prevalence of detecting HPV in the oral cavity (2.4%) and fingernails (3.8%) was low compared with the vagina (33.1%). Concordance across anatomical sites was poor (kappa < 0.20 for all comparisons). However, concurrent vaginal infection with the same HPV type (odds ratio [OR], 101.0; 95% confidence interval [CI], 31.4-748.6) and vaginal HPV viral load (OR per 1 log10 viral load increase, 2.2; 95% CI, 1.5-5.5) were each associated with fingernail HPV detection. Abnormal Papanicolaou history (OR, 11.1; 95% CI, 2.8-infinity), lifetime number of male vaginal sex partners at least 10 (OR vs. 0-3 partners, 5.0; 95% CI, 1.2-infinity), and lifetime number of open-mouth kissing partners at least 16 (OR vs. 0-15 partners, infinity; 95% CI, 2.6-infinity, by exact logistic regression) were each associated with oral HPV detection. CONCLUSIONS: Although our findings support HPV DNA deposition or autoinoculation between anatomical sites in mid-adult women, the rarity of HPV in the oral cavity and fingernails suggests that oral/fingernail HPV does not account for a significant fraction of HPV in genital sites. PMID- 26562697 TI - Adaptation of the HIV Care Continuum as a Method for Evaluating Syphilis and Gonorrhea Disease Control Activities in Los Angeles County. AB - BACKGROUND: Treatment verification and contact elicitation are core approaches used to control the spread of sexually transmitted diseases (STDs). Methodology adapted from the HIV care continuum is presented as an evaluation and communication tool for STD control activities. METHODS: Sexually transmitted disease surveillance and program data for Los Angeles County in 2013 were used to construct a 2-part continuum to examine syphilis (all stages) and gonorrhea outcomes among index patients and elicited contacts. The Index Case Continuum (Part 1) assesses the proportion of patients who were treated, assigned for interview, interviewed, and provided name and locating information for at least 1 contact. The Elicited Contact Continuum (Part 2) assesses the proportion of contacts who were located, interviewed, and treated. RESULTS: Among 3668 patients with syphilis, 97% (n = 3556) were treated, 72% (n = 2633) were interviewed, and 25% (n = 920) provided name and locating information for at least 1 contact. The corresponding numbers for 12,541 gonorrhea cases were 95% (n = 11,936), 45% (n = 5633), and 16% (1944), respectively. Among the 1392 contacts elicited from syphilis cases, 53% (n = 735) were either interviewed or determined to not need an interview and 43% (n = 595) were treated. The corresponding numbers for the 2323 contacts elicited from gonorrhea cases were 53% (n = 1221) and 46% (n = 1075), respectively. CONCLUSIONS: Adaptation of the HIV continuum is a useful tool for evaluating treatment verification and contact elicitation activities. In Los Angeles County, this approach revealed significant drop-offs in the proportion of index cases naming contacts and in the proportion of contacts who are interviewed and treated. PMID- 26562698 TI - Effects of Brief Messaging About Undiagnosed Infections Detected through HIV Testing Among Black and Latino Men Who Have Sex With Men in the United States. AB - We examined intent to get tested for HIV infection and use condoms among n = 604 uninfected black and Latino men who have sex with men after receiving brief information messaging that 1 in 10 minority men who have sex with men had HIV infection and did not know it. Information awareness, newness, believability, HIV testing cost willingness, and associated demographic variables were also assessed. PMID- 26562699 TI - Relationship of Estimated SHIV Acquisition Time Points During the Menstrual Cycle and Thinning of Vaginal Epithelial Layers in Pigtail Macaques. AB - BACKGROUND: HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. METHODS: Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. RESULTS: In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). CONCLUSIONS: These data provide a detailed picture of dynamic cycle related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection. PMID- 26562700 TI - Prevalence Estimates of Complicated Syphilis. AB - We reviewed 68 cases of possible neurosyphilis among 573 syphilis cases in King County, WA, from 3rd January 2012 to 30th September 2013; 7.9% (95% confidence interval, 5.8%-10.5%) had vision or hearing changes, and 3.5% (95% confidence interval, 2.2%-5.4%) had both symptoms and objective confirmation of complicated syphilis with either abnormal cerebrospinal fluid or an abnormal ophthalmologic examination. PMID- 26562701 TI - High Rate of beta-Globin DNA Detection Validates Self-Sampling in Herpes Simplex Virus Shedding Studies. AB - BACKGROUND: Self-sampling is a convenient, feasible, and acceptable way of collecting genital specimens, but the veracity of reported self-collection is difficult to verify. We investigated whether a host gene, beta-globin, can be used to confirm adequacy of self-collected mucosal and skin genital specimens in studies of genital herpes simplex virus type 2 (HSV-2) infection. METHODS: Herpes simplex virus type 2-seropositive adults self-collected daily anogenital and oral swabs. Mucosal samples were tested for HSV DNA using a real-time quantitative polymerase chain reaction assay. A real-time Taqman polymerase chain reaction detecting the beta-globin gene was used to quantify host cells. RESULTS: One hundred twelve participants collected 5559 genital and 2002 oral swabs. Sixty (54%) were women, 65% were HSV-2 seropositive, and 35% were HSV-1 and HSV-2 seropositive by Western blot. beta-globin DNA was detected in 99% and 93% of swabs obtained from women and men, respectively. The quantity of beta-globin DNA detected was significantly higher when HSV was present in genital swabs in women (0.1 log10 copies/mL; P = 0.001) and in men (0.6 log10 copies/mL; P < 0.001), but not in oral swabs in women (0.2 log10 copies/mL; P = 0.08) or men (0.0 log10 copies/mL; P = 0.70). CONCLUSIONS: Human beta-globin DNA detection rate was high, and the quantity obtained significantly increased with genital, but not oral HSV shedding. The high rate of beta-globin DNA detection is consistent with high adherence to study procedures in longitudinal studies of genital herpes shedding. PMID- 26562702 TI - Epidemiology of Sexually Transmitted Infections in Visitors for the London 2012 Olympic Games: A Review of Attendees at Sexual Health Services. AB - BACKGROUND: Mass gatherings and large sporting events, such as the Olympics, may potentially pose a risk of increased sexually transmitted infection (STI) transmission and increase burden on local STI services. The objectives of this analysis were to assess whether the STI profile of Olympic visitors differed from that of the local STI clinic population and to investigate what impact these visitors had on local STI services. METHODS: Self-administered questionnaires (completed by 29,292 patients) were used to determine the visitor status of patients attending 20 STI clinics, between July 20, 2012, and September 16, 2012, in the host cities, London and Weymouth. Using routine surveillance data from the Genitourinary Medicine Clinic Activity Dataset version 2, Olympic visitors were compared with usual attendees (local residents and non-Olympic visitors) in terms of their demographic characteristics, services utilized, and STIs diagnosed using univariate and multivariate methods. RESULTS: Compared with usual attendees, Olympic visitors were more likely to be heterosexual males (56.0% vs. 34.9%, P = 0.001), aged between 15 and 24 years of age (47.1% vs. 34.0%, P = 0.001), of white ethnicity (81.9% vs. 66.4%, P = 0.001), and born in Australasia, Asia, North America, or South America (18.8% vs. 12.0%, P = 0.006). Olympic visitors constituted 1% of new clinic attendances and were less likely to be diagnosed as having a new STI (adjusted odds ratio, 0.69; 95% confidence interval, 0.48-0.98; P = 0.040). CONCLUSIONS: In this first multisite study to examine the effect of Olympic visitors on local sexual health services, the 2012 Olympic Games was found to have minimal impact. This suggests that a "business as usual" approach would have been sufficient. PMID- 26562703 TI - Evaluating Quality of Care for Sexually Transmitted Infections in Different Clinical Settings. AB - BACKGROUND: We examined quality of care across different clinical settings within a large safety-net hospital in Massachusetts for patients presenting with penile discharge/dysuria or vaginal discharge. METHODS: Using a modified Delphi approach, a list of sex-specific sexually transmitted infection (STI) quality measures, covering 7 domains of clinical care (history, examination, laboratory testing, assessment, treatment, additional screening, counseling), was selected as standard of care by a panel of 5 STI experts representing emergency department (ED), obstetrics/gynecology (Ob/Gyn), family medicine (FM), primary care (PC), and infectious disease. Final measures were piloted with 50 charts per sex from the STI Clinic and age, sex, and visit date-matched charts from PC, FM, ED, and Ob/Gyn. Performance was scored as compliance among individual measures within 7 domains, standardized to add up to one to adjust for variable number of measures per domain, with an overall score of 7 indicating complete adherence to standards. RESULTS: Expert review process took 2 weeks and resulted in 24 and 34 final measures for male and female patients, respectively. Performance on 7 clinical domains ranged from 3.16 to 4.36 for male patients and 3.17 to 4.33 for female patients. Sexually transmitted infection clinic seemed to score higher on laboratory testing, additional screening, and counseling, but lower on examination and assessment, and ED seemed to score higher on examination and treatment, PC and FM on laboratory testing for male patients and on examination and treatment for female patients, and Ob/Gyn on treatment. CONCLUSIONS: An instrument to discern standard of care and identify strengths and weaknesses in specific domains of clinical documentation for patients presenting with STI complaints can be developed and implemented for quality evaluation across care settings. Further research is needed on whether these findings can be integrated into site-specific quality improvement processes and linked to cost analyses. PMID- 26562704 TI - Assessing the Changing Landscape of Sexual Health Clinical Service After the Implementation of the Affordable Care Act. AB - INTRODUCTION: Federal health reform has the potential to impact many public health services, especially sexual health clinics. To assess the impact of such reform within the Denver Sexual Health Clinic (DSHC), we conducted a survey of patients to better understand our client population and their care-seeking behavior. METHODS: Survey data were collected from patients attending the DSHC at 3 different points in time to ascertain insurance status, reasons for not having insurance, reasons for choosing care at the DSHC, and health care use over the past 12 months. RESULTS: A total of 1603 surveys were completed. Forty-two percent of participants were enrolled in health insurance at the time of visit. The percentage of patients with Medicaid increased more than 200% across the survey cycles. Cost was the main reason cited for not having insurance. Participants identified confidentiality and convenience among the top reasons for seeking care at the DSHC regardless of sex or insurance. Although there was no difference in health care use for sexual health services, individuals with health insurance were more likely to have used nonsexual health services in the past 12 months than those without insurance. CONCLUSIONS: Patients continue to visit the DSHC despite having health insurance. Sexual health clinics must work to understand what drives people to seek care so that they can better prepare for the future. PMID- 26562705 TI - The Effectiveness of Psychoeducational Intervention on Managing Symptom Clusters in Patients With Cancer: A Systematic Review of Randomized Controlled Trials. AB - BACKGROUND: Managing symptom clusters instead of single symptoms could be more beneficial in cancer care. Psychoeducational intervention (PEI) has been highlighted as a promising symptom intervention, but the effect of PEI in the management of cancer symptom clusters remains unknown. OBJECTIVE: The aim of this study was to evaluate the effectiveness of PEI on managing symptom clusters in patients with cancer. METHODS: Six databases were searched, together with hand searching, to identify eligible randomized controlled trials from the year 2001 to July 2014. Data selection, quality appraisal of studies, and data extraction were conducted independently by 2 reviewers. Data were synthesized by use of a systematic narrative approach, and meta-analysis was conducted when this was possible. RESULTS: Four eligible studies involving 343 cancer patients were included in the review. The methodological quality of the studies was generally fair. Symptom clusters seemed to improve with the provision of PEI. Meta-analysis shows significant improvement in functional performance. CONCLUSIONS: The evidence that PEI could alleviate cancer symptom clusters is encouraging but inconclusive in this review. Future well-designed investigations testing some commonly used PEI such as progressive muscle relaxation and patient education on various types of cancer symptom clusters are warranted. IMPLICATIONS FOR PRACTICE: This review suggests a promising role of PEI in managing cancer symptom clusters. Healthcare providers should increase their awareness of managing symptom clusters using PEI to yield more effective and efficient cancer care. PMID- 26562706 TI - World Day of Remembrance for Road Traffic Victims - November 15, 2015. PMID- 26562707 TI - Acute Effects of Loaded Half-Squat Jumps on Sprint Running Speed in Track and Field Athletes and Soccer Players. AB - The purpose of the study was to determine the acute responses to a jump squat protocol designed to induce postactivation potentiation on sprint running performance in experienced track and field athletes and soccer players. Twenty five regional level athletes (12 track and field: ~17 years; ~177 cm; ~73 kg and 13 soccer: ~18 years; ~175 cm; ~72 kg) performed 2 test sessions assessing 40-m sprint running performance in a balanced, crossover design. Dual-beam light timing gates measured 0-20 and 20-40 m sprint times before and after either 9 minutes of sitting (control) or 2 sets of 6 repetition half-squat jump with the load eliciting maximum power (experimental) conditions. Sprint performance was significantly enhanced over both 0-20 m (3.09 +/- 0.07 to 3.04 +/- 0.08 seconds; Delta ~1.5%; p <= 0.05) and 20-40 m (2.42 +/- 0.09 to 2.39 +/- 0.09 seconds; Delta ~1%; p <= 0.05) in track and field athletes only. Also, the magnitude of enhanced sprint performance was related to baseline 0-20 m sprint performance (r = 0.44; p = 0.028; n = 25). It seems that using loaded half-squat jumps to enhance sprint performance could be used in training of high-level young athletes. PMID- 26562708 TI - Effect of Preexercise Creatine Ingestion on Muscle Performance in Healthy Aging Males. AB - Preexercise creatine supplementation may have a beneficial effect on aging muscle performance. Using a double-blind, repeated measures, crossover design, healthy males (N = 9, 54.8 +/- 4.3 years; 92.9 +/- 11.5 kg; 179.2 +/- 11.1 cm) were randomized to consume creatine (20 g) and placebo (20 g corn starch maltodextrin), on 2 separate occasions (7 days apart), 3 hours before performing leg press and chest press repetitions to muscle fatigue (3 sets at 70% 1 repetition maximum; 1 minute rest between sets). There was a set main effect (p <= 0.05) for the leg press and chest press with the number of repetitions performed decreasing similarly for creatine and placebo. These results suggest that a bolus ingestion of creatine consumed 3 hours before resistance exercise has no effect on upper or lower-body muscle performance in healthy aging males. PMID- 26562709 TI - The Effect of Resistance Training and Different Sources of Postexercise Protein Supplementation on Muscle Mass and Physical Capacity in Sarcopenic Elderly Men. AB - The loss of muscle mass (sarcopenia) with aging is related to a progressive loss of muscle strength and physical capacity. Resistance exercise and milk-based protein supplementation have been demonstrated as significant countermeasures for sarcopenia and the loss of muscle strength. However, using high doses of proteins can act as a meal replacement in the elderly. Therefore, we sought to determine whether a standard supplementation (12 g per serving) of protein and resistance training could be an efficient strategy to promote muscle strength and physical capacity in sarcopenic men. Twenty-six participants were randomized in 3 groups in a double-blind control study. All the groups performed exercise and consumed a protein-rich supplement 12 g of protein, 7 g of essential amino acids from milk (n = 8), soy (n = 8), or rice milk (nonprotein control, n = 10). Body composition was measured using dual-energy x-ray absorptiometry. Strength was measured by 1 repetition maximum with different exercises. Different physical capacity measurements were assessed (timed up and go test, chair stand, and walking speed). The results indicated a significant increase in fat-free mass in all groups and changes in muscle strength, with no differences between groups. This study indicates that resistance training is an effective way to increase muscle mass and strength, regardless of protein supplementation. Higher doses of protein rich foods may have to be recommended to promote muscle mass gains when executing resistance exercise in elderly sarcopenic individuals. PMID- 26562710 TI - The Effect of Exertion and Sex on Vertical Ground Reaction Force Variables and Landing Mechanics. AB - The purpose of this investigation was to determine how exertion and sex affected a variety of vertical ground reaction force (VGRF) parameters during a jump landing task, including peak VGRF, peak VGRF asymmetry, loading rate, and loading rate asymmetry. Additionally, we wanted to determine whether landing mechanics changed after exertion as measured by the Landing Error Scoring System (LESS). Forty recreationally active participants (20 men and 20 women) completed jump landings from a 30-cm-high box onto force plates before and after repeated bouts of an exercise circuit until a specific rating of perceived exertion was achieved. Three-way (sex * time * limb) analyses of variance were used to analyze variables pre-exertion to postexertion. No significant 3-way interactions were observed for peak VGRF (p = 0.31) or loading rate (p = 0.14). Time by sex interactions were observed for peak VGRF (p = 0.02) and loading rate (p = 0.008). Post hoc analysis revealed that men increased landing force and loading rate after exertion while women did not. Landing mechanics, as assessed by total LESS score, were worse after exertion (p < 0.001) with increased frequency of errors for knee flexion <30 degrees at initial contact, lateral trunk flexion, and not flexing the hip during landing. Women may be more resistant to exertion compared with men and use different joint controls' strategies to cope with VGRF after exertion. However, VGRF asymmetry is not affected by sex and exertion. Limiting peak VGRF and addressing landing postures, especially after exertion, should be components of injury prevention strategies. PMID- 26562711 TI - Special Judo Fitness Test Level and Anthropometric Profile of Elite Spanish Judo Athletes. AB - Casals, C, Huertas, JR, Franchini, E, Sterkowicz-Przybycien, K, Sterkowicz, S, Gutierrez-Garcia, C, and Escobar-Molina, R. Special judo fitness test level and anthropometric profile of elite spanish judo athletes. J Strength Cond Res 31(5): 1229-1235, 2017-The aim of this study was to determine the anthropometric variables that best predict Special Judo Fitness Test (SJFT) performance. In addition, anthropometric profiles of elite Spanish judo athletes were compared by sex and age category (seniors and juniors). In this cross-sectional study, a total of 51 (29 females) athletes from the Spanish National Judo Team were evaluated during a competitive period. All athletes performed the SJFT and underwent an anthropometric assessment through skinfold thickness measurements. Mann-Whitney comparisons by sex and age category showed that males had significantly higher muscle mass and lower fat mass than females (p < 0.001), whereas juniors and seniors exhibited few differences in body composition. Linear regression analyses (stepwise method) were performed to explore the relationships between anthropometric characteristics and SJFT variables. Model 1 included sex, age category, and body mass as predictors. Body mass and sex significantly predicted the SJFT index (R = 0.27, p < 0.001); thus, both criteria should be considered before interpreting the test. The predictors of model 2 were quick assessment variables, including skinfolds, breadths, girths, and height. This regression model showed that the biceps skinfold significantly predicted the SJFT index in elite athletes (R = 0.31, p < 0.001). Model 3 included body compositions and somatotypes as predictors. Higher muscle and bone masses and lower ectomorphy were associated with better SJFT performance (R = 0.44, p < 0.001). Hence, training programs should attempt to increase the muscle mass percentage and reduce the upper arm fat, whereas the bone percentage could be considered in the selection of talented athletes in conjunction with other factors. PMID- 26562712 TI - Effects of Elastic Band Resistance Training on Glucose Control, Body Composition, and Physical Function in Women With Short- vs. Long-Duration Type-2 Diabetes. AB - This study examined whether the existing duration of type-2 diabetes influenced patient responses to progressive resistance training. Twenty-six women with type 2 diabetes were stratified into short- (3 +/- 2 years; n = 12) or long-standing (10 +/- 3 years; n = 14) disease groups. Patients participated in a high daily or high weekly frequency elastic band resistance training program that consisted of 2 daily sessions, 5 d.wk for 12 weeks. Glucose control, body composition, and physical function were evaluated pre- and posttraining. No significant diabetes duration * training interactions were detected for blood markers of glucose control (p > 0.05); however, there were significant main effects of training driven by comparable improvements in both cohorts (hemoglobin A1c, -13 to 18%; fasting glucose, -23 to 31%; postprandial glucose, -36 to 40%; insulin, -34 to 40%; C-peptide, -38 to 51%; p <= 0.05). Anthropometrics and body composition were also favorably modified in both the groups after training (weight, -5 to 9%; body mass index, -6 to 9%; waist-to-hip ratio, -3 to 5%; percent fat, -14 to 20%; p <= 0.05). Likewise, indices of physical function improved in both the groups after training (bicep curl repetitions, +15-33%; sit-and-stand repetitions, +45-47%; p <= 0.05). A few exceptions were noted in which patients with long-standing disease demonstrated greater pre-to-post gains (p <= 0.05) in grip strength (+11 13%) and peak exercise time (+19%) and load (+21%) during graded exercise, whereas those with shorter disease duration did not. Overall, these data suggest that patients with a long history of diabetes respond positively to resistance training and in a manner comparable to their recently diagnosed counterparts. Therefore, current inactivity in patients with long-standing disease should not deter from beginning an exercise program. PMID- 26562713 TI - Relationship Between Reactive Agility and Change of Direction Speed in Amateur Soccer Players. AB - The aim of the study was to assess the relationship between reactive agility and change of direction speed (CODS) among amateur soccer players using running tests with four directional changes. Sixteen amateur soccer players (24.1 +/- 3.3 years; 72.4 +/- 7.3 kg; 178.7 +/- 6 cm) completed CODS and reactive agility tests with four changes of direction using the SpeedCourtTM system (Globalspeed GmbH, Hemsbach, Germany). Countermovement jump (CMJ) height and maximal foot tapping count (completed in 3 seconds) were also measured with the same device. In the reactive agility test, participants had to react to a series of light stimuli projected onto a screen. Total time was shorter in the CODS test than in the reactive agility test (p < 0.001). Nonsignificant correlations were found among variables measured in the CODS, reactive agility, and CMJ tests. Low common variance (r = 0.03-0.18) was found between CODS and reactive agility test variables. The results of this study underscore the importance of cognitive factors in reactive agility performance and suggest that specific methods may be required for training and testing reactive agility and CODS. PMID- 26562714 TI - Heart Rate Responses of High School Students Participating in Surfing Physical Education. AB - Despite the nation's rising epidemic of childhood obesity and diabetes, schools struggle to promote physical activities that help reduce risks for cardiovascular disease. Emerging data suggest that adopting novel activities into physical education (PE) curriculum may serve as an effective strategy for increasing physical activity in children. The purpose of this investigation was to characterize activity in the water and heart rates (HRs) of high school students participating in surf PE courses. Twenty-four male (n = 20) and female (n = 4) high school students (mean age = 16.7 +/- 1.0 years) who were enrolled in surf PE courses at 2 high schools participated in this investigation. Daily measurements of surfing durations, average HR, and maximum HR were made on the students with HR monitors (PolarFT1) over an 8-week period. In addition, HR and activity in the water was evaluated during a single session in a subset of students (n = 11) using a HR monitor (PolarRCX5) and a video camera (Canon HD). Activity and HR were synchronized and evaluated in 5-second intervals during data analyses. The average duration that PE students participated in surfing during class was 61.7 +/- 1.0 minutes. Stationary, paddling, wave riding, and miscellaneous activities comprised 42.7 +/- 9.5, 36.7 +/- 7.9, 2.9 +/- 1.4, and 17.8 +/- 11.4 percent of the surf session, respectively. The average and maximum HRs during these activities were 131.1 +/- 0.9 and 177.2 +/- 1.0 b.min, respectively. These data suggest that high school students participating in surf PE attained HRs and durations that are consistent with recommendations with cardiovascular fitness and health. In the future, PE programs should consider incorporating other action sports into their curriculum to enhance cardiovascular health. PMID- 26562715 TI - Reliability of the Tuck Jump Injury Risk Screening Assessment in Elite Male Youth Soccer Players. AB - Read, PJ, Oliver, JL, de Ste Croix, MBA, Myer, GD, and Lloyd, RS. Reliability of the tuck jump injury risk screening assessment in elite male youth soccer players. J Strength Cond Res 30(6): 1510-1516, 2016-Altered neuromuscular control has been suggested as a mechanism for injury in soccer players. Ligamentous injuries most often occur during dynamic movements, such as decelerations from jump-landing maneuvers where high-risk movement patterns are present. The assessment of kinematic variables during jump-landing tasks as part of a preparticipation screen is useful in the identification of injury risk. An example of a field-based screening tool is the repeated tuck jump assessment. The purpose of this study was to analyze the within-subject variation of the tuck jump screening assessment in elite male youth soccer players. Twenty-five pre peak height velocity (PHV) and 25 post-PHV elite male youth soccer players from the academy of a professional English soccer club completed the assessment. A test-retest design was used to explore the within-subject intersession reliability. Technique was graded retrospectively against the 10-point criteria set out in the screening protocol using two-dimensional video cameras. The typical error range reported for tuck jump total score (0.90-1.01 in pre-PHV and post-PHV players respectively) was considered acceptable. When each criteria was analyzed individually, kappa coefficient determined that knee valgus was the only criterion to reach substantial agreement across the two test sessions for both groups. The results of this study suggest that although tuck jump total score may be reliably assessed in elite male youth soccer players, caution should be applied in solely interpreting the composite score due to the high within-subject variation in a number of the individual criteria. Knee valgus may be reliably used to screen elite youth male soccer players for this plyometric technique error and for test-retest comparison. PMID- 26562716 TI - Effect of Intermittent Hypoxic Training Followed by Intermittent Hypoxic Exposure on Aerobic Capacity of Long Distance Runners. AB - Effects of intermittent hypoxic training (IHT) are still controversial and detraining effects remain uninvestigated. Therefore, we investigated (a) whether IHT improves aerobic capacity; (b) whether aerobic detraining occurs post-IHT; and (c) whether intermittent hypoxic exposure (IHE) at rest reduces a possible aerobic detraining post-IHT. Twenty eight runners (21 men/7 women; 36 +/- 2 years; maximal oxygen uptake [V[Combining Dot Above]O2max] 55.4 +/- 1.3 ml.kg.min) participated in a single-blinded placebo-controlled trial. Twice a week, 1 group performed 6 weeks of IHT (n = 11), followed by 4 weeks of IHE (n = 11) at rest (IHT+IHE group). Another group performed 6 weeks of IHT (n = 10), followed by 4 weeks of normoxic exposure (NE, n = 9) at rest (IHT+NE group). A control group performed 6 weeks of normoxic training (NT, n = 7), followed by 4 weeks of NE (n = 6) at rest (NT+NE group). Hematological and submaximal/maximal aerobic measurements were conducted in normoxia at pretraining, posttraining, and postexposure. Hemoglobin concentration did not change, but lactate threshold and running economy improved in all groups at posttraining (p <= 0.05 vs. pretraining). Ventilatory threshold, respiratory compensation point, and V[Combining Dot Above]O2max increased after IHT (IHT+IHE group: 7.3, 5.4, and 9.2%, respectively; IHT+NE group: 10.7, 7.5, and 4.8%; p <= 0.05 vs. pretraining), but not after NT (-1.1, -1.0, and -3.8%; p > 0.05 vs. pretraining). Such IHT-induced adaptations were maintained at postexposure (p > 0.05 vs. postexposure). In conclusion, IHT induced further aerobic improvements than NT. These additional IHT adaptations were maintained for 4 weeks post-IHT, regardless of IHE. PMID- 26562717 TI - Faster Futsal Players Perceive Higher Training Loads and Present Greater Decreases in Sprinting Speed During the Preseason. AB - The aims of this study were to assess the speed-power characteristics of professional futsal players before and after a 9-week preseason and to explore possible relationships with internal training loads. Ten under-20 professional Brazilian futsal players performed unloaded (squat jump [SJ] and countermovement jump [CMJ]) and loaded (jump squat [JS]) jumps and a 20-m sprint test before and after the preseason. Weekly training loads as measured by session rating of perceived exertion (s-RPE) varied between 2,179 and 5,519 a.u. The magnitude based inference statistics revealed that performance in the SJ, CMJ, and 20-m sprint very likely decreased (effect size [ES] = -0.64, -0.49, and -0.92, respectively), whereas mean propulsive power in the JS likely increased (ES = 0.42) in response to the preseason. The Pearson coefficient of correlation between velocity in the 20 m sprint test and s-RPE during the first 2 weeks of training was 0.66 (p <= 0.05) while no significant correlation was detected between total s-RPE (i.e., 9 weeks) and changes in the power-speed tests. The baseline 20-m sprint velocity was very largely and inversely (r = -0.90) correlated with the change in the 20-m sprint performance. In conclusion, futsal preseason training leads to impaired unloaded vertical jump and sprint test performance, with speed decreasing more in faster than slower players. In addition, because of the large correlation between baseline sprint ability and s RPE, coaches are advised to assess sprinting performance at the beginning of the preseason to finely adjust the training stimuli to each athlete. PMID- 26562719 TI - Tin Disulfide Nanoplates on Graphene Nanoribbons for Full Lithium Ion Batteries. AB - A nanocomposite material made of layered tin disulfide (SnS2) nanoplates vertically grown on reduced graphene oxide nanoribbons (rGONRs) has been successfully developed as an anode in lithium ion batteries by a facile method. At a rate of 0.4 A/g, the material exhibits a high discharge capacity of 823 mAh/g even after 800 cycles. It shows excellent rate stability when the current density varies from 0.1 to 3.0 A/g with a Coulombic efficiency larger than 99%. In order to demonstrate the anode material for practical applications, SnS2 rGONR/LiCoO2 full cells were constructed. To the best of our knowledge, this is the first time that a full cell has been successfully developed using metal chalcogenides as an anode. The full cell delivers a high capacity of 642 mAh/g at 0.2 A/g, superior rate, and cycling stability after long-term cycling. Moreover, the full cell has a high output working voltage of 3.4 V. These excellent lithium storage performances in half and full cells can be mainly attributed to the synergistic effect between the highly conductive network of rGONRs and the high lithium-ion storage capability of layered SnS2 nanoplates. PMID- 26562720 TI - Molecular Mechanism underlying PRMT1 Dimerization for SAM Binding and Methylase Activity. AB - Protein arginine methyltransferases (PRMTs) catalyze the posttranslational methylation of arginine, which is important in a range of biological processes, including epigenetic regulation, signal transduction, and cancer progression. Although previous studies of PRMT1 mutants suggest that the dimerization arm and the N-terminal region of PRMT1 are important for activity, the contributions of these regions to the structural architecture of the protein and its catalytic methylation activity remain elusive. Molecular dynamics (MD) simulations performed in this study showed that both the dimerization arm and the N-terminal region undergo conformational changes upon dimerization. Because a correlation was found between the two regions despite their physical distance, an allosteric pathway mechanism was proposed based on a network topological analysis. The mutation of residues along the allosteric pathways markedly reduced the methylation activity of PRMT1, which may be attributable to the destruction of dimer formation and accordingly reduced S-adenosyl-L-methionine (SAM) binding. This study provides the first demonstration of the use of a combination of MD simulations, network topological analysis, and biochemical assays for the exploration of allosteric regulation upon PRMT1 dimerization. These findings illuminate the results of mechanistic studies of PRMT1, which have revealed that dimer formation facilitates SAM binding and catalytic methylation, and provided direction for further allosteric studies of the PRMT family. PMID- 26562721 TI - Uniting Ruthenium(II) and Platinum(II) Polypyridine Centers in Heteropolymetallic Complexes Giving Strong Two-Photon Absorption. AB - New trinuclear RuPt2 and heptanuclear RuPt6 complex salts are prepared by attaching Pt(II) 2,2':6',2"-terpyridine (tpy) moieties to Ru(II) 4,4':2',2":4",4"'-quaterpyridine (qpy) complexes. Characterization includes single crystal X-ray structures for both polymetallic species. The visible absorption bands are primarily due to Ru(II) -> qpy metal-to-ligand charge transfer (MLCT) transitions, according to time-dependent density functional theory (TD-DFT) calculations. These spectra change only slightly on Pt coordination, while the orange-red emission from the complexes shows corresponding small red-shifts, accompanied by decreases in intensity. Cubic molecular nonlinear optical behavior has been assessed by using Z-scan measurements. These reveal relatively high two-photon absorption (2PA) cross sections sigma2, with maximal values of 301 GM at 834 nm (RuPt2) and 523 GM at 850 nm (RuPt6) when dissolved in methanol or acetone, respectively. Attaching Pt(II)(tpy) moieties triples or quadruples the 2PA activities when compared with the Ru(II)-based cores. PMID- 26562722 TI - Domino Strategy for the Stereoselective Construction of Angularly Fused Tricyclic Ethers. AB - A stereoselective synthesis of decahydrofuro[3,2-d]isochromene derivatives has been achieved by the condensation of 2-cyclohexenylbutane-1,4-diol with aldehydes in the presence of a stochiometric amount of BF3.OEt2 in dichloromethane at -78 degrees C. Similarly, the condensation of 2-cyclopentenylbutan-1,4-diol with aldehydes provides the corresponding octahydro-2H-cyclopenta[c]furo[2,3-d]pyran derivatives in good yields with high diastereoselectivity. It is an elegant strategy for the quick construction of tricyclic architectures with four contiguous stereogenic centers in a single step. These tricyclic frameworks are the integral part of numerous natural products. PMID- 26562723 TI - Amino Acid Residues in the Putative Transmembrane Domain 11 of Human Organic Anion Transporting Polypeptide 1B1 Dictate Transporter Substrate Binding, Stability, and Trafficking. AB - Organic anion transporting polypeptides (OATPs, gene symbol SLCO) are membrane proteins that mediate the sodium-independent transport of a wide range of endogenous and exogenous compounds. Due to their broad substrate specificity, wide tissue distribution, and involvement in drug-drug interactions, OATPs have been considered as key players in drug absorption, distribution, and excretion. Transmembrane domains (TMs) are crucial structural features involved in proper functions of many transporters. According to computer-based modeling and previous studies of our laboratory and others, TM11 of OATP1B1 may face the substrate interaction pocket and thus play an important role in the transport function of the protein. Alanine-scanning of the transmembrane domain identified seven critical amino acid residues within the region. Further analysis revealed that alanine substitution of these residues resulted in reduced protein stability, which led to significantly decreased protein expression on the plasma membrane. In addition, all mutants exhibited an altered Km for ES uptake (either high affinity or low affinity component, or both), though Km for taurocholate transport only changed in R580A, G584A, and F591A. These results suggested that critical residues in TM11 not only affect protein stability of the transporter, but its interaction with substrates as well. The identification of seven essential residues out of 21 TM amino acids highlighted the importance of this transmembrane domain in the proper function of OATP1B1. PMID- 26562724 TI - Controllable Drug Release System in Living Cells Triggered by Enzyme-Substrate Recognition. AB - Vehicles can deliver the drug molecules into cells, yet immunoreaction of the commonly used capping agents and release triggers limit their biomedical use. This shortcoming might be circumvented through replacing these chemicals with certain biomolecules. Here, we show a new and facile way to encapsulate the drug delivery vehicles and release the cargos in a highly controllable manner via modulating supramolecular interactions between enzyme, substrate, and vehicle. The cargo release from the vehicles within cells can be achieved upon substrate treatment. Yeast cells were used, allowing for a fast and cost-effective way for imaging and morphological analysis. We believe this new platform can be readily extended to various carrier systems for different purposes based on shifting the recognition pattern of enzyme-substrate pairs. PMID- 26562725 TI - A retrospective study of 51,781 adult oral and maxillofacial biopsies. AB - BACKGROUND: Few studies have compared patient and anatomic characteristics across the broad scope of oral and maxillofacial disease seen in dental clinics. The authors conducted a study to make these comparisons by surveying a large sample of histologically diagnosed oral and maxillofacial lesions in a US adult population. METHODS: A total of 51,781 specimens biopsied from 51,781 adult patients were received by an oral pathology service over 13 years (2001-2015) and analyzed. A description of patients' sex and age at diagnosis, as well as the anatomic site of biopsy was given for diagnoses of 10 oral disease types, including malignant neoplasm, benign neoplasm, infectious, reactive, potentially malignant, developmental, healthy tissue, immune dysfunction, physical trauma, and other. RESULTS: The authors reported reactive lesions were the most prevalent disease type found in the sample (74.9%). Malignant diagnoses comprised 1.97% of all biopsies. The 3 most prevalent diagnoses in this study included benign keratosis, chronic apical periodontitis, and radicular cyst. Different anatomic sites, patient age groups, and sexes show different distributions of disease. CONCLUSIONS: Certain disease types and diagnoses were found to have a higher prevalence by sex, among particular age groups, and in certain anatomic sites. PRACTICAL IMPLICATIONS: This information provides clinicians with a detailed and broad scope of the variety of oral and maxillofacial lesions processed at an oral pathology service and may assist practitioners in forming clinical impressions and differential diagnoses. PMID- 26562726 TI - Techniques and materials used by general dentists during endodontic treatment procedures: Findings from The National Dental Practice-Based Research Network. AB - BACKGROUND: Little is known about which materials and techniques general dentists (GDs) use during endodontic procedures. The objectives were to quantify GDs' use of specific endodontic tools, quantify inappropriate use, and ascertain whether inappropriate use is associated with GDs' practice characteristics. METHODS: GDs in The National Dental Practice-Based Research Network reported in a questionnaire materials and techniques they use during endodontic procedures. RESULTS: Among eligible GDs, 1,490 (87%) participated. Most (93%; n = 1,383) used sodium hypochlorite to irrigate. The most commonly used sealers were zinc oxide eugenol (43%) and resin (40%), followed by calcium hydroxide (26%). Most (62%; n = 920) used a compaction obturation technique; 36% (n = 534) used a carrier-based method. Most (96%; n = 1,423) used gutta-percha as a filler; 5% used paste fillers. Few used irrigants (n = 46), techniques (n = 49), or fillers (n = 10) that investigators classified as inappropriate. CONCLUSIONS: GDs use a broad range of endodontic techniques and materials, often adapting to newer technologies as they become available. Few GDs use tools that the investigators classified as inappropriate. PRACTICAL IMPLICATIONS: GDs use many types of endodontic techniques and materials, but only a small percentage of them are inappropriate. PMID- 26562727 TI - Triangular radiolucent lesion of the mandible. PMID- 26562728 TI - Massive oral bleeding after full-mouth extraction in a patient with B-cell lymphocytic leukemia/small lymphocytic lymphoma reversed with recombinant activated factor VII. AB - BACKGROUND AND OVERVIEW: Full-mouth extraction can be associated with intraoral bleeding, which usually is controlled with local hemostatic measures. Recombinant activated factor VII (rFVIIa) occasionally is used to stop bleeding in a variety of off-label indications, with the main argument curtailing its use being thrombotic events. The authors describe the use of rFVIIa for bleeding after full mouth extraction in a patient with undiagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. CASE DESCRIPTION: A 72-year-old man underwent full-mouth extraction (18 teeth). The next day, the patient experienced massive oral bleeding. The authors administered tranexamic acid, aminocaproic acid, and a total of 12 units of packed red blood cells in addition to local hemostatic measures without control of bleeding. On postoperative day 10, the authors administered 5,000 micrograms of rFVIIa, and within 2 hours oral the bleeding ceased. The authors performed flow cytometry and diagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Unexplained massive oral bleeding despite adequate local hemostatic measures should prompt further investigations for underlying bleeding or coagulation disorders. The authors describe the successful use of rFVIIa in massive oral bleeding. Further studies are mandatory to study the effectiveness of this drug for this off-label indication. PMID- 26562729 TI - Dental care after an emergency department visit for dental problems among adults enrolled in Medicaid. AB - BACKGROUND: Dental emergency department (ED) visits are increasing nationally, but EDs provide only palliative care. The authors examine time to subsequent dentist visit within 6 months after the ED visit, as well as the effect of having a dentist visit in the prior year. METHODS: Using 2010-2012 Iowa Medicaid claims data, the authors identified adults with an index dental ED visit. The authors examined the claims data for a subsequent dentist visit within the next 6 months. The authors used Kaplan-Meier curves and log-rank tests for bivariate analyses. The authors included a dentist visit in the year before the index ED visit, subsequent ED visits, and sociodemographic characteristics in a Cox multivariable regression model. RESULTS: A total of 2,430 adults enrolled in Medicaid satisfied the study inclusion criteria. Within 6 months, 52.4% had a subsequent dentist visit, 12.0% lost Medicaid eligibility, and 35.6% did not have subsequent dentist visit. Bivariate and multivariable analyses revealed that nonwhites, those without a dentist visit in the prior year, and those with subsequent ED visits had a significantly lower rate of subsequent dentist visits. CONCLUSIONS: Almost one-half of adults with a dental ED visit did not visit a dentist in the next 6 months. Adults who did not visit a dentist in the past year and those with repeated ED visits may be living with unresolved dental problems that can affect their quality of life. PRACTICAL IMPLICATIONS: Adults without a dentist visit in the past year and those who visit ED repeatedly can be targeted by ED diversion programs because they are at higher risk of not receiving follow-up dental care. PMID- 26562730 TI - Perspectives on evolving dental care payment and delivery models. AB - BACKGROUND: Health care reform is well under way in the United States as reflected in evolving delivery, financing, and payment approaches that are affecting medicine ahead of dentistry. METHODS: The authors explored health systems changes under way, distinguished historical and organizational differences between medicine and dentistry, and developed alternative models to characterize the relationships between these professions. The authors explored a range of medical payment approaches, including those tied to objective performance metrics, and their potential application to dentistry. RESULTS: Advances in understanding the essential role of oral health in general health have pulled dentistry into the broader discussion of care integration and payment reform. Dentistry's fit with primary and specialty medical care may take a variety of forms. Common provider payment approaches in dentistry-fee-for service, capitation, and salary-are tied insufficiently to performance when measured as either health processes or health outcomes. CONCLUSIONS: Dentistry can anticipate potential payment reforms by observing changes already under way in medicine and by understanding alternative payment approaches that are tied to performance metrics, such as those now in development by the Dental Quality Alliance and others. PRACTICAL IMPLICATIONS: Novel forms of dental practice may be expected to evolve continuously as medical-dental integration and payment reforms that promote accountability evolve. PMID- 26562731 TI - Use of dental services by immigration status in the United States. AB - BACKGROUND: There is limited research with mixed findings comparing differences in oral health outcomes and the use of dental services by immigration status. The authors conducted a study by reviewing nationally representative data to describe differences in dental care among noncitizens, naturalized citizens, and US-born citizens in the United States. METHODS: The authors used nationally representative data from the 2008-2012 Medical Expenditure Panel Survey to examine dental care for US-born citizens, naturalized citizens, and noncitizens 18 years and older. Total analytical sample size was 98,107 adults. They used multivariate logistic regression to model dental service use adjusting for confounding factors. RESULTS: Naturalized citizens and noncitizens were significantly less likely to have at least 1 dental visit within 12 months (39.5% and 23.1%, respectively) compared with US-born citizens (43.6%; P < .001). Among users, a smaller proportion of comprehensive examination visits were for naturalized citizens and noncitizens (75.9% and 71.4%, respectively) compared with US-born citizens (82.8%; P < .01). Noncitizen visits to dentists were also more likely to involve tooth extraction compared with those of US-born citizens (11.3% versus 8.8%; P < .01). Multivariate logistic regression suggests both non- and naturalized citizens had lower adjusted odds of having a comprehensive examination compared with US-born citizens during a visit (P < .01). CONCLUSIONS: Noncitizens and naturalized citizens had a lower rate of dental service use, and noncitizens were more likely to have had tooth extraction compared with US-born citizens. PRACTICAL IMPLICATIONS: Increased outreach efforts tailored to noncitizens and naturalized citizens who are at high risk of experiencing dental problems are needed, particularly to address misperceptions on the necessity of preventive dental visits. PMID- 26562732 TI - Short-term use of nonsteroidal anti-inflammatory drugs and adverse effects: An updated systematic review. AB - BACKGROUND: In this article, the authors examine the available scientific evidence regarding adverse effects of short-term use of nonsteroidal anti inflammatory drugs (NSAIDs). Short-term use was defined as 10 days or fewer. METHODS: The authors reviewed randomized controlled clinical trials and cohort and case-controlled clinical studies published between 2001 and June 2015 in which the investigators reported on the safety of nonselective cyclooxygenase inhibitors and of cyclooxygenase-2 selective inhibitor NSAIDs. RESULTS: The systematic review process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines allowed the authors to identify 40 studies that met the inclusion criteria. CONCLUSIONS: On the basis of the available scientific evidence, NSAIDs may be considered relatively safe drugs when prescribed at the most effective dose and for the shortest duration of time, which was defined to be 10 days or fewer. PRACTICAL IMPLICATIONS: Although the US Food and Drug Administration recommends the use of NSAIDs beyond 10 days to be accompanied by a consultation with a health care provider, the use of NSAIDs may be considered relatively safe when prescribed at the most effective dose and for the shortest duration of time, which was defined as 10 days or fewer. Exceptions would be for patients at risk of developing NSAID-exacerbated respiratory disease, patients with prior myocardial infarction who are receiving antithrombotic therapy, patients with asthma, and patients with a history of renal disease. PMID- 26562733 TI - Prevalence of erosive tooth wear and associated factors in a group of Mexican adolescents. AB - BACKGROUND: Erosive tooth wear is the irreversible loss of dental hard tissue as a result of chemical processes. When the surface of a tooth is attacked by acids, the resulting loss of structural integrity leaves a softened layer on the tooth's surface, which renders it vulnerable to abrasive forces. The authors' objective was to estimate the prevalence of erosive tooth wear and to identify associated factors in a sample of 14- to 19-year-old adolescents in Mexico. METHODS: The authors performed a cross-sectional study on a convenience sample (N = 417) of adolescents in a school in Mexico City, Mexico. The authors used a questionnaire and an oral examination performed according to the Lussi index. RESULTS: The prevalence of erosive tooth wear was 31.7% (10.8% with exposed dentin). The final logistic regression model included age (P < .01; odds ratio [OR], 1.64; 95% confidence interval [CI], 1.26-2.13), high intake of sweet carbonated drinks (P = .03; OR, 1.81; 95% CI, 1.06-3.07), and xerostomia (P = .04; OR, 2.31; 95% CI, 1.05-5.09). CONCLUSIONS: Erosive tooth wear, mainly on the mandibular first molars, was associated with age, high intake of sweet carbonated drinks, and xerostomia. PRACTICAL IMPLICATIONS: Knowledge regarding erosive tooth wear in adolescents with relatively few years of exposure to causal factors will increase the focus on effective preventive measures, the identification of people at high risk, and early treatment. PMID- 26562734 TI - A rapidly enlarging gingival mass in an 11-year-old boy. PMID- 26562735 TI - Pre- and postoperative dexamethasone does not reduce bleaching-induced tooth sensitivity: A randomized, triple-masked clinical trial. AB - BACKGROUND: Tooth sensitivity (TS) is the most common side effect of dental bleaching therapies. Dexamethasone has been used with tooth bleaching to reduce TS. The efficacy of dexamethasone for this purpose has not been well studied. METHODS: The authors conducted a triple-masked, randomized, clinical trial with a parallel design involving 63 healthy participants who received either a placebo or dexamethasone. The placebo or dexamethasone (8 milligrams) was administered 1 hour before the in-office bleaching (35% hydrogen peroxide) and extra doses of 4 mg were administered every 6 hours for a total of 48 hours. TS was recorded on 2 scales: visual analog scale (0-10) and numeric rating scale (0-4) in different periods. The color evaluations were performed before and 1 month after dental bleaching with visual shade guides VITA Classical (VITA Zahnfabrik) and VITA Bleachedguide 3D-MASTER (VITA Zahnfabrik), and for a shade guide evaluation, the authors used a digital spectrophotometer, VITA Easyshade (VITA Zahnfabrik). The absolute risk of TS was evaluated by a Fisher exact test. Data of TS intensity using the NRS scale for the 2 groups were compared with Mann-Whitney and Friedman tests, whereas data from the visual analog scale were evaluated by 2-way repeated measures analysis of variance. The color changes between groups were compared using a t test (alpha = .05). RESULTS: In both groups, the authors detected a high risk of TS, which was approximately 90%. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. CONCLUSIONS: The use of dexamethasone before bleaching did not reduce the risk and intensity of bleaching-induced TS. PRACTICAL IMPLICATIONS: The use of the steroidal anti-inflammatory agent dexamethasone was not capable of preventing TS arising from in-office dental bleaching. PMID- 26562736 TI - Measuring up: Implementing a dental quality measure in the electronic health record context. AB - BACKGROUND: Quality improvement requires using quality measures that can be implemented in a valid manner. Using guidelines set forth by the Meaningful Use portion of the Health Information Technology for Economic and Clinical Health Act, the authors assessed the feasibility and performance of an automated electronic Meaningful Use dental clinical quality measure to determine the percentage of children who received fluoride varnish. METHODS: The authors defined how to implement the automated measure queries in a dental electronic health record. Within records identified through automated query, the authors manually reviewed a subsample to assess the performance of the query. RESULTS: The automated query results revealed that 71.0% of patients had fluoride varnish compared with the manual chart review results that indicated 77.6% of patients had fluoride varnish. The automated quality measure performance results indicated 90.5% sensitivity, 90.8% specificity, 96.9% positive predictive value, and 75.2% negative predictive value. CONCLUSIONS: The authors' findings support the feasibility of using automated dental quality measure queries in the context of sufficient structured data. Information noted only in free text rather than in structured data would require using natural language processing approaches to effectively query electronic health records. PRACTICAL IMPLICATIONS: To participate in self-directed quality improvement, dental clinicians must embrace the accountability era. Commitment to quality will require enhanced documentation to support near-term automated calculation of quality measures. PMID- 26562737 TI - Are topical fluorides effective for treating incipient carious lesions?: A systematic review and meta-analysis. AB - BACKGROUND: This systematic review and meta-analysis evaluated the effectiveness of professional topical fluoride application (gels or varnishes) on the reversal treatment of incipient enamel carious lesions in primary or permanent dentition. METHODS: Literature searching was carried out by the authors in PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, Turning Research Into Practice, and ClinicalTrials.gov to verify the clinical trials available about the outcome. From 754 potentially eligible studies, 21 were selected for full-text analysis, 5 were included for review, and 3 for meta-analysis. The statistical analysis was performed only for studies assessing fluoride varnish; there were insufficient data to perform it for fluoride gel studies. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Pooled-effect estimates were expressed as the weighted mean difference between groups. RESULTS: The therapeutic methods ranged considerably regarding the fluoride application protocols. There was a significant trend of effectiveness of fluoride varnish on the reversal of incipient enamel carious lesions (P < .05). High heterogeneity was found in the meta-analysis. CONCLUSIONS: Fluoride varnish seems to be an effective treatment for the reversal of incipient carious lesions in primary and permanent dentition; however, further clinical trials concerning efficacy of topical fluorides for treating those lesions are still required, mainly regarding the fluoride gel. PRACTICAL IMPLICATIONS: Considering the scientific evidence on topical fluorides, pediatric dentists can use fluoride varnishes as an adjuvant for the treatment of active white-spot lesions in primary or permanent dentition. PMID- 26562738 TI - Open contacts adjacent to dental implant restorations: Etiology, incidence, consequences, and correction. AB - BACKGROUND: The aim of this investigation was to evaluate the potential causes, clinical significance, and treatment of open contacts between dental implant restorations and adjacent natural teeth. TYPES OF STUDIES REVIEWED: The authors searched the dental literature for clinical trials in humans that addressed the incidence of open contacts that develop after implant restorations are placed next to teeth. RESULTS: The authors found 5 studies in which the investigators addressed the incidence of open contacts after implant restorations are inserted next to teeth. Results from these studies indicated that an interproximal gap developed 34% to 66% of the time after an implant restoration was inserted next to a natural tooth. This event occurred as early as 3 months after prosthetic rehabilitation, usually on the mesial aspect of a restoration. CONCLUSIONS: The occurrence of an interproximal separation next to an implant restoration was greater than anticipated. It appears that force vectors cause tooth movement and an implant functions like an ankylosed tooth. PRACTICAL IMPLICATIONS: Clinicians should inform patients of the potential to develop interproximal gaps adjacent to implant restorations, which may require repair or replacement of implant crowns or rehabilitation of adjacent teeth. Furthermore, steps should be taken to check the continuity of the arch periodically. If the clinician detects an open contact, it is prudent to monitor for signs or symptoms of pathosis so that prosthetic repair of the gap can be initiated, if needed. These problems could add to treatment costs and decrease overall patient satisfaction related to implant treatment. PMID- 26562739 TI - Ionic Functionalization of Hydrophobic Colloidal Nanoparticles To Form Ionic Nanoparticles with Enzymelike Properties. AB - Inorganic colloidal nanoparticles (NPs) stabilized by a layer of hydrophobic surfactant on their surfaces have poor solubility in the aqueous phase, thus limiting their application as biosensors under physiological conditions. Here we report a simple model to ionize various types of hydrophobic colloidal NPs, including FePt, cubic Fe3O4, Pd, CdSe, and NaYF4 (Yb 30%, Er 2%, Nd 1%) NPs, to multicharged (positive and negative) NPs via ligand exchange. Surfaces of neutral hydrophobic NPs were converted to multicharged ions, thus making them soluble in water. Furthermore, peroxidase-like activity was observed for ionic FePt, Fe3O4, Pd, and CdSe NPs, of which FePt and CdSe catalyzed the oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) to the blue-colored product in the absence of H2O2, while Pd and Fe3O4 catalyzed the oxidization of TMB in the presence of H2O2. With the benefit of the ionic functionalization protocols described herein, colloidal NPs should gain wider use as biomarkers, nanozymes, and biosensors. PMID- 26562740 TI - Organocatalytic Nonclassical Trienamine Activation in the Remote Alkylation of Furan Derivatives. AB - A new approach for the stereoselective remote alkylation of furan derivatives is reported. The reaction of 5-alkylfurfurals with nitroolefins as electrophilic counterparts occurs at their exocyclic epsilon-position and proceeds through the intermediacy of a nonclassical catalytic trienamine intermediate. The aminocatalyst bearing a H-bonding unit is used to control the stereochemical reaction outcome confirming the usefulness of such catalytic systems for the remote functionalizations of carbonyl compounds. Target products with two adjacent stereogenic centers are obtained in excellent yields and with good to moderate stereoselectivities. PMID- 26562741 TI - Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity. AB - A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 MUM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 MUM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups. PMID- 26562742 TI - International long-term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0-19 years. AB - To enhance understanding of etiology, we examined international population-based cancer incidence data for lymphoid leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma and myeloid leukemia among children aged 0-19. Based on temporal trends during 1978-2007 in 24 populations, lymphoid leukemia and myeloid leukemia incidence rates generally have not changed greatly and differences in rates for non-Hodgkin and for Hodgkin lymphoma have diminished in some regions. Lymphoid leukemia rates during 2003-2007 in 54 populations varied about 10-fold, with rates highest in US white Hispanics (50.2 per million person-years) and Ecuador (48.3) and lowest in US blacks (20.4), Tunisia (17.7) and Uganda (6.9). Non Hodgkin lymphoma rates varied 30-fold, with very high rates in sub-Saharan Africa (146.0 in Malawi and 54.3 in Uganda) and low rates (<= 10) in some Asian populations (China, Japan, India, the Philippines and Thailand) and U.S. Asian Pacific Islanders, eastern and northern European populations and Puerto Rico. Hodgkin lymphoma rates varied 15-fold, with rates highest in Italy (21.3) and lowest in China (1.7). Myeloid leukemia rates varied only about fivefold, with rates highest in the Philippines and Korea (exceeding 14.0) and lowest in Eastern Europe (5.9 in Serbia and 5.3 in the Czech Republic) and Uganda (2.7). The boy/girl average incidence rate ratios were 2.00 or lower. Age-specific patterns differed among the four hematopoietic malignancies, but were generally consistent within major categories world-wide, except for non-Hodgkin lymphoma. A systematic world-wide approach comparing postulated etiologic factors in low- versus high risk populations may help clarify the etiology of these childhood malignancies. PMID- 26562743 TI - Cutinase promotes dry esterification of cotton cellulose. AB - Cutinase from Thermobifida fusca was used to esterify the hydroxyl groups of cellulose with the fatty acids from triolein. Cutinase and triolein were pre adsorbed on cotton and the reaction proceeded in a dry state during 48 h at 35 degrees C. The cutinase-catalyzed esterification of the surface of cotton fabric resulted in the linkage of the oleate groups to the glycoside units of cotton cellulose. The superficial modification was confirmed by performing ATR-FTIR on treated cotton samples and by MALDI-TOF analysis of the liquors from the treatment of the esterified cotton with a crude cellulase mixture. Modified cotton fabric also showed a significant increase of hydrophobicity. This work proposes a novel bio-based approach to obtain hydrophobic cotton. PMID- 26562745 TI - Continuous noninvasive ventilatory support as an alternative to invasive TMV. PMID- 26562744 TI - Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels. AB - OBJECTIVE: Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper foetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N = 205 matched pairs). Data were stratified according to prepregnancy or first trimester BMI. RESULTS: Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r = 0.422, P < 0.001). Maternal and neonatal fT3 were also significantly associated with birthweight (beta = 0.155, P = 0.027 and beta = 0.171, P = 0.018, respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0.86 +/- 0.17 vs 0.95 +/- 0.22, P < 0.01). CONCLUSION: Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a nonhuman primate model, we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of foetal overgrowth and childhood obesity. PMID- 26562746 TI - Exacerbated and prolonged inflammation impairs wound healing and increases scarring. AB - Altered inflammation in the early stage has long been assumed to affect subsequent steps of the repair process that could influence proper wound healing and remodeling. However, the lack of explicit experimental data makes the connection between dysregulated wound inflammation and poor wound healing elusive. To bridge this gap, we used the established rabbit ear hypertrophic scar model for studying the causal effect of dysregulated inflammation. We induced an exacerbated and prolonged inflammatory state in these wounds with the combination of trauma-related stimulators of pathogen-associated molecular patterns from heat killed Pseudomonas aeruginosa and damage-associated molecular patterns from a dermal homogenate. In stimulated wounds, a heightened and lengthened inflammation was observed based on quantitative measurements of IL-6 expression, tissue polymorphonuclear leukocytes infiltration, and tissue myeloperoxidase activity. Along with the high level of inflammation, wound healing parameters (epithelial gap and others) at postoperative day 7 and 16 were significantly altered in stimulated wounds compared to unstimulated controls. By postoperative day 35, scar elevation of stimulated wounds was higher than that of control wounds (scar elevation index: 1.90 vs. 1.39, p < 0.01). Moreover, treatment of these inflamed wounds with Indomethacin (at concentrations of 0.01, 0.1, and 0.4%) reduced scar elevation but with adverse effects of delayed wound closure and increased cartilage hypertrophy. In summary, successful establishment of this inflamed wound model provides a platform to understand these detrimental aspects of unchecked inflammation and to further test agents that can modulate local inflammation to improve wound outcomes. PMID- 26562747 TI - Characterization of Abeta Monomers through the Convergence of Ensemble Properties among Simulations with Multiple Force Fields. AB - Amyloid beta (Abeta) monomers represent a base state in the pathways of aggregation that result in the fibrils and oligomers implicated in the pathogenesis of Alzheimer's disease (AD). The structural properties of these intrinsically disordered peptides remain unclear despite extensive experimental and computational investigations. Further, there are mutations within Abeta that change the way the peptide aggregates and are known to cause familial AD (FAD). Here, we analyze the ensembles of different isoforms (Abeta42 and Abeta40) and mutants (E22Delta, D23N, E22K, E22G, and A2T in Abeta40) of Abeta generated with all-atom replica exchange molecular dynamics (REMD) simulations on the MUs/replica time scale. These were run using three different force field/water model combinations: OPLS-AA/L and TIP3P ("OPLS"), AMBER99sb-ILDN and TIP4P-Ew ("ILDN"), as well as CHARMM22* and TIP3SP ("CHARMM"). Despite fundamental changes in simulation parameters, we find that the resulting ensembles demonstrate a strong convergence in structural properties. In particular, antiparallel contacts between L17-A21 and A30-L34 are prevalent in ensembles of Abeta40, directly forming beta sheets in the OPLS and ILDN combinations. A21-A30 commonly forms an interceding region that rarely interacts with the rest of the peptide. Further, Abeta42 contributes new beta hairpin motifs involving V40-I41 in both OPLS and ILDN. However, the structural flexibility of the central region and the electrostatic interactions that characterize it are notably different between the different conditions. Further, for OPLS, each of the FAD mutations disrupts central bend character and increases the polymorphism of antiparallel contacts across the central region. However, the studied mutations in the ILDN set primarily encourage more global contacts involving the N-terminus and the central region, and promote the formation of new beta topologies that may seed different aggregates involved in disease phenotypes. These differences aside, the large degree of agreement between simulation sets across multiple force fields provides a generalizable characterization of Abeta that is also consistent with experimental data and models. PMID- 26562749 TI - Electrically Tunable van der Waals Interaction in Graphene-Molecule Complex. AB - van der Waals (vdW) interactions play a central role in the surface-related physics and chemistry. Tuning of the correlated charge fluctuation in a vdW complex is a plausible way of modulating the molecules interaction at the atomic surface. Here, we report the vdW interaction tunability of the graphene-CO2 complex by combining the first-principles calculations with the vdW density functionals and the time evaluation measurements of CO2 molecules adsorption/desorption on graphene under an external electric field. The field dependent charge transfer within the complex unveils the controllable tuning of CO2 from acceptor to donor. Meanwhile, the configuration of the adsorbed molecule, the equilibrium distance from graphene and O-C-O bonding angle, is modified accordingly. The range of electrical tunability is a unique feature for each type of molecule. PMID- 26562748 TI - Role of mechanical ventilation in the airborne transmission of infectious agents in buildings. AB - Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses. PMID- 26562750 TI - Free-Energy Barriers and Reaction Mechanisms for the Electrochemical Reduction of CO on the Cu(100) Surface, Including Multiple Layers of Explicit Solvent at pH 0. AB - The great interest in the photochemical reduction from CO2 to fuels and chemicals has focused attention on Cu because of its unique ability to catalyze formation of carbon-containing fuels and chemicals. A particular goal is to learn how to modify the Cu catalysts to enhance the production selectivity while reducing the energy requirements (overpotential). To enable such developments, we report here the free-energy reaction barriers and mechanistic pathways on the Cu(100) surface, which produces only CH4 (not C2H4 or CH3OH) in acid (pH 0). We predict a threshold potential for CH4 formation of -0.52 V, which compares well to experiments at low pH, -0.45 to -0.50 V. These quantum molecular dynamics simulations included ~5 layers of explicit water at the water/electrode interface using enhanced sampling methodology to obtain the free energies. We find that that chemisorbed hydroxyl-methylene (CH-OH) is the key intermediate determining the selectivity for methane over methanol. PMID- 26562751 TI - Development of an Unnatural Amino Acid Incorporation System in the Actinobacterial Natural Product Producer Streptomyces venezuelae ATCC 15439. AB - Many Actinobacteria, most notably Streptomyces, produce structurally diverse bioactive natural products, including ribosomally synthesized peptides, by multistep enzymatic pathways. The use of site-specific genetic incorporation of unnatural amino acids to investigate and manipulate the functions of natural product biosynthetic enzymes, enzyme complexes, and ribosomally derived peptides in these organisms would have important implications for drug discovery and development efforts. Here, we have designed, constructed, and optimized unnatural amino acid systems capable of incorporating p-iodo-l-phenylalanine and p-azido-l phenylalanine site-specifically into proteins in the model natural product producer Streptomyces venezuelae ATCC 15439. We observed notable differences in the fidelity and efficiency of these systems between S. venezuelae and previously used hosts. Our findings serve as a foundation for using an expanded genetic code in Streptomyces to address questions related to natural product biosynthesis and mechanism of action that are relevant to drug discovery and development. PMID- 26562753 TI - Core muscle characteristics during walking of patients with multiple sclerosis. AB - The purpose of this study was to investigate core muscle characteristics during walking in patients with multiple sclerosis (MS). Eight patients (4 men) with relapsing-remitting MS (aged 44.9 +/- 8.6 yr) and sex-matched controls (37.9 +/- 8.4 yr) walked on a treadmill for 15 min at a self-selected speed. Positron emission tomography/computed tomography imaging was used to measure core muscle activity immediately after walking based on glucose uptake. Activity was not different between the MS and control group for any of the identified muscles (p > 0.28). Within the MS group, side differences in activity were identified in the lateral flexor group, the external and internal obliques, and the rectus abdominis (p < 0.05), with the less-affected side being activated more. Furthermore, greater muscle volume was found on the more-affected side of the transversus abdominis, quadratus lumborum, and the low-back extensor group (p < 0.03). These muscle characteristics suggest patients with MS utilize compensatory mechanisms during walking to maintain balance and posture. These strategies likely result in increased muscle energy cost and early fatigability. PMID- 26562754 TI - New Challenges. PMID- 26562752 TI - Control of microtubule organization and dynamics: two ends in the limelight. AB - Microtubules have fundamental roles in many essential biological processes, including cell division and intracellular transport. They assemble and disassemble from their two ends, denoted the plus end and the minus end. Significant advances have been made in our understanding of microtubule plus-end tracking proteins (+TIPs) such as end-binding protein 1 (EB1), XMAP215, selected kinesins and dynein. By contrast, information on microtubule minus-end-targeting proteins (-TIPs), such as the calmodulin-regulated spectrin-associated proteins (CAMSAPs) and Patronin, has only recently started to emerge. Here, we review our current knowledge of factors, including microtubule-targeting agents, that associate with microtubule ends to control the dynamics and function of microtubules during the cell cycle and development. PMID- 26562755 TI - Endurance Exercise Reduces Hepatic Fat Content and Serum Fibroblast Growth Factor 21 Levels in Elderly Men. AB - CONTEXT: Age-related hepatic fat accumulation increases the risk of cardiometabolic diseases, and the fibroblast growth factor (FGF) 21-resistant state caused by fatty liver underlies the pathogenesis of these diseases. OBJECTIVE: Previous studies suggested that a higher level of cardiorespiratory fitness was associated with both lower hepatic fat content and serum FGF21 levels; however, the effect of endurance exercise on hepatic fat content and serum FGF21 concentration has not been studied. Therefore, we aimed to elucidate whether endurance exercise reduced hepatic fat content and serum FGF21 levels. DESIGN: This is a randomized crossover trial. SETTING: The study setting was an institutional practice. PATIENTS: Thirty-three elderly Japanese men participated in the study. INTERVENTION: The intervention was a 5-week endurance exercise program comprising three cycle ergometer sessions per week. MAIN OUTCOME MEASURES: Hepatic fat content was assessed by proton magnetic resonance spectroscopy, and serum FGF21 level was determined by ELISA. RESULTS: A 5-week endurance exercise program decreased the hepatic fat content and serum FGF21 levels without weight loss, and the changes were higher in the exercise period than in the control period (P = .021 and P = .026, respectively). Correlation analysis demonstrated that only the change in hepatic fat content was significantly and positively correlated with change in serum FGF21 levels (r = 0.366, P = .006). CONCLUSIONS: A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels. These findings suggest that endurance exercise modulates hepatic fat content and FGF21 resistance, regardless of obesity status. PMID- 26562756 TI - Corrigenda. PMID- 26562757 TI - Corrigenda. PMID- 26562758 TI - The Relationship between Childhood Obesity, Low Socioeconomic Status, and Race/Ethnicity: Lessons from Massachusetts. AB - BACKGROUND: Previous studies have shown race/ethnicity, particularly African American and/or Hispanic status, to be a predictor of overweight/obese status in children. However, these studies have failed to adjust for low socioeconomic status (SES). This study assessed whether race/ethnicity remained an independent predictor of childhood obesity when accounting for variations in SES (low-income) among communities in Massachusetts. METHODS: This study was based on 2009 summarized data from 68 Massachusetts school districts with 111,799 students in grades 1, 4, 7, and 10. We studied the relationship between the rate of overweight/obese students (mean = 0.32; range = 0.10-0.46), the rate of African American and Hispanic students (mean = 0.17; range = 0.00-0.90), and the rate of low-income students (mean = 0.27; range = 0.02-0.87) in two and three dimensions. The main effect of the race/ethnicity rate, the low-income rate, and their interaction on the overweight and obese rate was investigated by multiple regression modeling. RESULTS: Low-income was highly associated with overweight/obese status (p < 0.0001), whereas the effect of race/ethnicity (p = 0.27) and its interaction (p = 0.23) with low-income were not statistically significant. For every 1% increase in low-income, there was a 1.17% increase in overweight/obese status. This pattern was observed across all African American and Hispanic rates in the communities studied. CONCLUSIONS: Overweight/obese status was highly prevalent among Massachusetts students, varying from 10% to 46% across communities. Although there were higher rates of overweight/obese status among African American and Hispanic students, the relationship disappeared when controlling for family income. Our findings suggest low SES plays a more significant role in the nation's childhood obesity epidemic than race/ethnicity. PMID- 26562759 TI - Long-Range Communication Network in the Type 1B Bone Morphogenetic Protein Receptor. AB - Protein-protein interactions are recognized as a fundamental phenomenon that is intimately associated with biological functions and thus are ideal targets for developing modulators for regulating biological functions. A challenge is to identify a site that is situated away from but functionally connected to the protein-protein interface. We employed bone morphogenetic proteins (BMPs) and their receptors as a model system to develop a strategy for identifying such a network of communication. Accordingly, using computational analyses with the COREX/BEST algorithm, we uncovered an overall pattern connecting various regions of BMPR-1B ectodomain, including the four conserved residues in the protein protein interface. In preparation for testing the long-range effects of mutations of distal residues for future studies, we examined the extent of measurable perturbation of the four conserved residues by determination of the conformation and relative affinities of these BMPR-1B mutants for ligands BMP-2, -6, and -7 and GDF-5. Results suggest no significant structural changes in the receptor but do suggest that the four residues play different roles in defining ligand affinity and both intra- and intermolecular interactions play a role in defining ligand affinity. Thus, these results established two primary but necessary goals: (1) the baseline knowledge of perturbation of conserved interfacial residues for future reference and (2) the ability of the computational approach to identify the distal residues connecting to the interfacial residues. The data presented here provide the foundation for future experiments to identify the effects of distal residues that affect the specificity and affinity of BMP recognition. Protein-protein interactions are integral reactions in essentially all biological activities such as gene regulation and age-related development. Often, diseases are consequences of the alteration of these intermacromolecular interactions, which are thus recognized as a legitimate target for developing modulators for regulating biological functions. One approach is to design ligands that bind to the protein-protein interface. Another is to identify an allosteric site, an advantage of which is bypassing the potential challenge in competing for high affinity interfacial interactions or a specific interface in a superassembly of multiple macromolecules. However, a challenge of this approach is identifying a site that is situated away from but functionally connected to the protein-protein interface. PMID- 26562760 TI - Panitumumab as a possible cause of hematospermia: what is the mechanism? PMID- 26562761 TI - Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy? AB - Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease. PMID- 26562762 TI - A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids. AB - Short chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity. Based on experimental evidence, we hypothesised that odd-chain SCFAs may possess anti mitotic capabilities in colon cancer cells by disrupting microtubule (MT) structural integrity via dysregulation of beta-tubulin isotypes. MT dynamic instability is an essential characteristic of MT cellular activity. We report a minimal deterministic model that takes a novel approach to explore the hypothesised pathway by triggering spontaneous oscillations to represent MT dynamic behaviour. The dynamicity parameters in silico were compared to those reported in vitro. Simulations of untreated and butyrate (even-chain length) treated cells reflected MT behaviour in interphase or untreated control cells. The propionate and valerate (odd-chain length) simulations displayed increased catastrophe frequencies and longer periods of MT-fibre shrinkage. Their enhanced dynamicity was dissimilar to that observed in mitotic cells, but parallel to that induced by MT-destabilisation treatments. Antimicrotubule drugs act through upward or downward modulation of MT dynamic instability. Our computational modelling suggests that metabolic engineering of the microbiome may facilitate managing CRC risk by predicting outcomes of SCFA treatments in combination with AMDs. PMID- 26562763 TI - Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus: A 5-Year Longitudinal Study. AB - IMPORTANCE: It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. OBJECTIVE: To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. EXPOSURE: The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3 mW/cm2 irradiance. MAIN OUTCOMES AND MEASURES: Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. RESULTS: Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) MUm (range, 372-497 MUm). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm2 in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm2 in the corneas of patients with stage 1 or 2 keratoconus was reduced 51% (mean difference, 10.7 mm/mm2 [95% CI, 6.8-14.6 mm/mm2]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm2 [95% CI, 4.7-12.4 mm/mm2]; P < .001) despite recovery of touch sensitivity to normal levels by 6 months. Preoperatively, more frequent nerve loops, crossings, and greater crossing angles were observed in the corneas of patients with keratoconus compared with healthy corneas. Postoperatively, the frequency of nerve looping increased, crossings were more frequent, and nerve tortuosity increased. Wide field mosaics indicated persistent disrupted orientation of the regenerating subbasal nerves 5 years after CXL. CONCLUSIONS AND RELEVANCE: Keratoconus is characterized by a neurotrophic deficit and altered nerve morphology that CXL treatment does not address, despite providing a positive biomechanical effect in the stroma. Given the widespread use of CXL in the management of patients with keratoconus, the progression of abnormal innervation after CXL should be recognized. PMID- 26562764 TI - Incidence of Suicide in Patients With Head and Neck Cancer. AB - IMPORTANCE: Suicide rates among patients with cancer in the US are significantly higher than those of the general population. To our knowledge, large cohort studies examining suicide rates among patients with head and neck cancer have not been performed. OBJECTIVE: To identify incidence rate, trends, and risk factors of suicide in patients with cancer of the head and neck. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of geographic areas served by the Surveillance, Epidemiology, and End Results (SEER) program. In total, 350,413 cases of patients with head and neck cancer were recorded within the SEER registry between 1973 and 2011. Data analyses were performed in 2014. Incidence data were calculated from the subset of that population that had the cause of death category coded as "suicide and self-inflicted injury." EXPOSURES: Patients diagnosed as having a primary cancer of the head and neck region. MAIN OUTCOMES AND MEASURES: Influence of demographic factors, anatomic site of tumor, disease stage, and time since diagnosis on risk for suicide. RESULTS: Among 350,413 SEER registry patients with head and neck cancer, observed for 2,263,376 person-years, 857 suicides were identified with an age-, sex-, and race-adjusted suicide rate of 37.9/100,000 person-years. In contrast, the US general population suicide rate was 11.8 per 100,000 person-years. Suicide rates were higher in those treated with radiation alone (standardized mortality ratio [SMR], 5.12; 95% CI, 3.83 6.41) compared with those treated with surgery alone (SMR, 2.57; 95% CI, 1.66 3.49). The highest suicide risk was seen in patients with cancers of the hypopharynx (SMR, 13.91; 95% CI, 11.78-16.03) and larynx (SMR, 5.48; 95% CI, 4.14 6.81). CONCLUSIONS AND RELEVANCE: Patients with head and neck cancer have more than 3 times the incidence of suicide compared with the general US population. Furthermore, suicide rates were highest among those with cancers of the larynx and hypopharynx. PMID- 26562765 TI - Downregulation of the sodium channel Nav1.6 by potential transcriptomic deregulation may explain sensory deficits in critical illness neuropathy. AB - AIMS: Sepsis patients and other patients in the critical care settings are at very high risk of mortality due to the primary illness. However, a fraction of patients, even after showing initial clinical improvement, deteriorates relentlessly at later stages. Increasingly, it is being identified that this is mostly due to dysfunction of the neurological system. MAIN METHODS: We obtained peripheral nerve biopsies from the sural nerve from ICU patients. Nav1.6 expression was significantly diminished. The expression of cellular membrane anchoring protein for Nav1.6, ankyrin, remained unaffected, suggesting that genomic repression may be responsible for the diminished expression of the sodium channels. We examined the expression of two regulatory transcription factors: (a) a positive regulator YY1 that binds to the promoter region of sodium channels and (b) an upstream negative neuronal regulator REST. KEY FINDINGS: REST expression was significantly elevated, while YY1 expression was diminished. Finally, we also observed that the cholinergic synthetic enzyme acyltransferase was also significantly diminished in sensory nerve lysates. Finally, circulating antibodies was detected in the peripheral blood against all the major sodium channels Nav1.6, 1.8 and 1.9, which contribute to the development and propagation of action potentials. SIGNIFICANCE: This may potentially explain why its dysfunction affects neurological functions across all systems of the body during critical illness. The underlying mechanism of why the expression of the REST transcriptional factor is affected in critical illnesses remains our future goals of investigation. PMID- 26562766 TI - Characterization of silver nanoparticle-infused tissue adhesive for ophthalmic use. AB - In this work, we demonstrate the successful enhancement of breaking strength, adhesive strength, and antibacterial efficacy of ophthalmic tissue adhesive (2 octyl cyanoacrylate) by doping with silver nanoparticles, and investigate the effects of nanoparticle size and concentration. Recent work has shown that silver nanoparticles are a viable antibacterial additive to many compounds, but their efficacy in tissue adhesives was heretofore untested. Our results indicate that doping the adhesive with silver nanoparticles reduced bacterial growth by an order of magnitude or more; nanoparticle size and concentration had minimal influence in the range tested. Tensile breaking strength of polymerized adhesive samples and adhesive strength between a T-shaped support and excised porcine sclera were measured using a universal testing machine according to ASTM (formerly American Society for Testing and Materials) standard techniques. Both tests showed significant improvement with the addition of silver nanoparticles. The enhanced mechanical strength and antibacterial efficacy of the doped adhesive supports the use of tissue adhesives as a viable supplement or alternative to sutures. PMID- 26562767 TI - Case-case studies: an innovative tool in the field of outbreak investigation. PMID- 26562769 TI - Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and lethality from phosgene. AB - Phosgene (CG), a toxic inhalation and industrial hazard, causes bronchoconstriction, vasoconstriction and associated pathological effects that could be life threatening. Ion channels of the transient receptor potential (TRP) family have been identified to act as specific chemosensory molecules in the respiratory tract in the detection, control of adaptive responses and initiation of detrimental signaling cascades upon exposure to various toxic inhalation hazards (TIH); their activation due to TIH exposure may result in broncho- and vasoconstriction. We studied changes in the regulation of intracellular free Ca(2+) concentration ([Ca(2+)]i) in cultures of human bronchial smooth muscle cells (BSMC) and human pulmonary microvascular endothelial cells (HPMEC) exposed to CG (16ppm, 8min), using an air/liquid interface exposure system. CG increased [Ca(2+)]i (p<0.05) in both cell types, The CG-induced [Ca(2+)]i was blocked (p<0.05) by two types of TRP channel blockers, SKF-96365, a general TRP channel blocker, and RR, a general TRPV (vanilloid type) blocker, in both BSMC and HPMEC. These effects correlate with the in vivo efficacies of these compounds to protect against lung injury and 24h lethality from whole body CG inhalation exposure in mice (8-10ppm*20min). Thus the TRP channel mechanism appears to be a potential target for intervention in CG toxicity. PMID- 26562768 TI - Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs. AB - Amorphous silica nanoparticles (NPs) possess unique material properties that make them ideal for many different applications. However, the impact of these materials on human and environmental health needs to be established. We investigated nonporous silica NPs both bare and modified with amine functional groups (3-aminopropyltriethoxysilane (APTES)) in order to evaluate the effect of surface chemistry on biocompatibility. In vitro data showed there to be little to no cytotoxicity in a human lung cancer epithelial cell line (A549) for bare silica NPs and amine-functionalized NPs using doses based on both mass concentration (below 200MUg/mL) and exposed total surface area (below 14m(2)/L). To assess lung inflammation, C57BL/6 mice were administered bare or amine functionalized silica NPs via intra-tracheal instillation. Two doses (0.1 and 0.5mg NPs/mouse) were tested using the in vivo model. At the higher dose used, bare silica NPs elicited a significantly higher inflammatory response, as evidence by increased neutrophils and total protein in bronchoalveolar lavage (BAL) fluid compared to amine-functionalized NPs. From this study, we conclude that functionalization of nonporous silica NPs with APTES molecules reduces murine lung inflammation and improves the overall biocompatibility of the nanomaterial. PMID- 26562771 TI - Toxicokinetics of perfluorooctane sulfonate in rabbits under environmentally realistic exposure conditions and comparative assessment between mammals and birds. AB - This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085MUg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36MUg PFOS/L serum for rabbits, slightly above one-half of the 65MUg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory species. PMID- 26562770 TI - Conceptual approaches for treatment of phosgene inhalation-induced lung injury. AB - Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civilian population in cases of accidental or intentional release. Several of these chemicals have no known medical countermeasures for their toxic effects. Phosgene is a highly toxic industrial chemical which was used as a chemical warfare agent in WWI. Exposure to phosgene causes latent, non-cardiogenic pulmonary edema which can result in respiratory failure and death. The mechanisms of phosgene-induced pulmonary injury are not fully identified, and currently there is no efficacious countermeasure. Here, we provide a proposed mechanism of phosgene-induced lung injury based on the literature and from studies conducted in our lab, as well as provide results from studies designed to evaluate survival efficacy of potential therapies following whole-body phosgene exposure in mice. Several therapies were able to significantly increase 24h survival following an LCt50-70 exposure to phosgene; however, no treatment was able to fully protect against phosgene-induced mortality. These studies provide evidence that mortality following phosgene toxicity can be mitigated by neuro- and calcium-regulators, antioxidants, phosphodiesterase and endothelin receptor antagonists, angiotensin converting enzymes, and transient receptor potential cation channel inhibitors. However, because the mechanism of phosgene toxicity is multifaceted, we conclude that a single therapeutic is unlikely to be sufficient to ameliorate the multitude of direct and secondary toxic effects caused by phosgene inhalation. PMID- 26562772 TI - Grouping chemicals for health risk assessment: A text mining-based case study of polychlorinated biphenyls (PCBs). AB - As many chemicals act as carcinogens, chemical health risk assessment is critically important. A notoriously time consuming process, risk assessment could be greatly supported by classifying chemicals with similar toxicological profiles so that they can be assessed in groups rather than individually. We have previously developed a text mining (TM)-based tool that can automatically identify the mode of action (MOA) of a carcinogen based on the scientific evidence in literature, and it can measure the MOA similarity between chemicals on the basis of their literature profiles (Korhonen et al., 2009, 2012). A new version of the tool (2.0) was recently released and here we apply this tool for the first time to investigate and identify meaningful groups of chemicals for risk assessment. We used published literature on polychlorinated biphenyls (PCBs) persistent, widely spread toxic organic compounds comprising of 209 different congeners. Although chemically similar, these compounds are heterogeneous in terms of MOA. We show that our TM tool, when applied to 1648 PubMed abstracts, produces a MOA profile for a subgroup of dioxin-like PCBs (DL-PCBs) which differs clearly from that for the rest of PCBs. This suggests that the tool could be used to effectively identify homogenous groups of chemicals and, when integrated in real-life risk assessment, could help and significantly improve the efficiency of the process. PMID- 26562773 TI - Arterial Decellularized Scaffolds Produced Using an Innovative Automatic System. AB - There is still an unmet clinical need for small-caliber artery substitution. Decellularized scaffolds in tissue engineering represent a promising solution. We have developed an innovative system for the automatic decellularization of blood vessels, used to process pig arteries. The system is able to automatically drive a decellularization process in a safe and reliable environment, with complex time patterns, using up to three different decellularization solutions, and providing at the same time a physical stress to improve the decellularization. The decellularization of pig arteries was evaluated by means of histology, DNA quantification and mechanical testing. Outcomes showed scaffolds with no cellular or nuclear remnants and a well-preserved tissue structure, corroborated by mechanical properties similar to native tissue. Decellularized scaffolds were seeded on the inner layer with human endothelial cells and implanted as iliac artery replacement in 4 pharmacologically immune-compromised pigs. This chimeric model was performed as a very preliminary evaluation to investigate the performances of these scaffolds in vivo, and to investigate the fate of seeded cells. Recipients were sacrificed on day 14 and day 70 after surgery, and vessels were found to be patent and with no evidence of thrombi formation. The inner layer was covered by endothelial cells, and the migration of cells positive for alpha-smooth-muscle actin was observed from the outer layer towards the tunica media. Intriguingly, the endothelial cells on explanted vessels were entirely derived from the host while the seeded cells were lost. In conclusion, this work presents a novel tool for a safe and controlled production of arterial scaffolds, with good decellularization outcomes and a good performance in a short-term, large-animal implantation. PMID- 26562775 TI - Correction: Base Station Placement Algorithm for Large-Scale LTE Heterogeneous Networks. PMID- 26562774 TI - Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models. AB - Cancer genomes contain vast amounts of somatic mutations, many of which are passenger mutations not involved in oncogenesis. Whereas driver mutations in protein-coding genes can be distinguished from passenger mutations based on their recurrence, non-coding mutations are usually not recurrent at the same position. Therefore, it is still unclear how to identify cis-regulatory driver mutations, particularly when chromatin data from the same patient is not available, thus relying only on sequence and expression information. Here we use machine-learning methods to predict functional regulatory regions using sequence information alone, and compare the predicted activity of the mutated region with the reference sequence. This way we define the Predicted Regulatory Impact of a Mutation in an Enhancer (PRIME). We find that the recently identified driver mutation in the TAL1 enhancer has a high PRIME score, representing a "gain-of target" for MYB, whereas the highly recurrent TERT promoter mutation has a surprisingly low PRIME score. We trained Random Forest models for 45 cancer related transcription factors, and used these to score variations in the HeLa genome and somatic mutations across more than five hundred cancer genomes. Each model predicts only a small fraction of non-coding mutations with a potential impact on the function of the encompassing regulatory region. Nevertheless, as these few candidate driver mutations are often linked to gains in chromatin activity and gene expression, they may contribute to the oncogenic program by altering the expression levels of specific oncogenes and tumor suppressor genes. PMID- 26562776 TI - Expression of PprI from Deinococcus radiodurans Improves Lactic Acid Production and Stress Tolerance in Lactococcus lactis. AB - PprI is a general switch protein that regulates the expression of certain proteins involved in pathways of cellular resistance in the extremophilic bacterium Deinococcus radiodurans. In this study, we transformed pprI into Lactococcus lactis strain MG1363 using the lactococcal shuttle vector pMG36e and investigated its effects on the tolerance and lactic acid production of L. lactis while under stress. PprI was stably expressed in L. lactis as confirmed by western blot assays. L. lactis expressing PprI exhibited significantly improved resistance to oxidative stress and high osmotic pressure. This enhanced cellular tolerance to stressors might be due to the regulation of resistance-related genes (e.g., recA, recO, sodA, and nah) by pprI. Moreover, transformed L. lactis demonstrated increased lactic acid production, attributed to enhanced lactate dehydrogenase activity. These results suggest that pprI can improve the tolerance of L. lactis to environmental stresses, and this transformed bacterial strain is a promising candidate for industrial applications of lactic acid production. PMID- 26562777 TI - Social Network Analysis Reveals the Negative Effects of Attention Deficit/Hyperactivity Disorder (ADHD) Symptoms on Friend-Based Student Networks. AB - INTRODUCTION: Social network analysis has emerged as a promising tool in modern social psychology. This method can be used to examine friend-based social relationships in terms of network theory, with nodes representing individual students and ties representing relationships between students (e.g., friendships and kinships). Using social network analysis, we investigated whether greater severity of ADHD symptoms is correlated with weaker peer relationships among elementary school students. METHODS: A total of 562 sixth-graders from two elementary schools (300 males) provided the names of their best friends (maximum 10 names). Their teachers rated each student's ADHD symptoms using an ADHD rating scale. RESULTS: The results showed that 10.2% of the students were at high risk for ADHD. Significant group differences were observed between the high-risk students and other students in two of the three network parameters (degree, centrality and closeness) used to assess friendship quality, with the high-risk group showing significantly lower values of degree and closeness compared to the other students. Moreover, negative correlations were found between the ADHD rating and two social network analysis parameters. CONCLUSION: Our findings suggest that the severity of ADHD symptoms is strongly correlated with the quality of social and interpersonal relationships in students with ADHD symptoms. PMID- 26562778 TI - Activity of Herbal Medicines on Plasmodium falciparum Gametocytes: Implications for Malaria Transmission in Ghana. AB - BACKGROUND: Malaria still remains a major health issue in Ghana despite the introduction of Artemisinin-based combination therapy (ACT) coupled with other preventative measures such as the use of insecticide treated nets (ITNs). The global quest for eradication of malaria has heightened the interest of identifying drugs that target the sexual stage of the parasite, referred to as transmission-blocking drugs. This study aimed at assessing the efficacy and gametocydal effects of some commonly used herbal malaria products in Ghana. METHODOLOGY/PRINCIPAL FINDINGS: After identifying herbal anti-malarial products frequently purchased on the Ghanaian market, ten of them were selected and lyophilized. In vitro drug sensitivity testing of different concentrations of the herbal products was carried out on asexual and in vitro generated gametocytes of the 3D7 strain of Plasmodium falciparum. The efficacies of the products were assessed by microscopy. Cultures containing low dose of RT also produced the least number of late stage gametocytes. Two of the herbal products CM and RT inhibited the growth of late stage gametocytes by > 80% at 100 MUg/ml whilst KG was the most inhibitory to early stage gametocytes at that same concentration. However at 1 MUg/ml, only YF significantly inhibited the survival of late stage gametocytes although at that same concentration YF barely inhibited the survival of early stage gametocytes. CONCLUSIONS/SIGNIFICANCE: Herbal product RT (Aloe schweinfurthii, Khaya senegalensis, Piliostigma thonningii and Cassia siamea) demonstrated properties of a highly efficacious gametocydal product. Low dose of herbal product RT exhibited the highest gametocydal activity and at 100 MUg/ml, RT exhibited >80% inhibition of late stage gametocytes. However inhibition of asexual stage parasite by RT was not optimal. Improving the asexual inhibition of RT could convert RT into an ideal antimalarial herbal product. We also found that generally C. sanguinolenta containing herbal products exhibited gametocydal activity in addition to high asexual efficacy. Herbal products with high gametocydal activity can help in the fight to reduce malaria transmission. PMID- 26562779 TI - Cytotoxic and apoptotic effects of leptocarpin, a plant-derived sesquiterpene lactone, on human cancer cell lines. AB - Sesquiterpene lactones have attracted much attention in drug research because they present a series of biological activities such as anticancer, antifungal, anti-inflammatory, antimicrobial and antioxidant. Leptocarpin (LTC) is a sesquiterpene lactone isolated from a native Chilean plant, Leptocarpha rivularis, which has been widely used in traditional medicine by Mapuche people. Previous work has demonstrated that LTC decreases cell viability of cancer cell lines. In this contribution, we analyze the mechanism of LTC cytotoxicity on different cancer cell lines. The results show that in all cases LTC induces an apoptotic process and inhibition of NF-kappaB. Apoptosis has been confirmed by observing condensation of chromatin, nuclear fragmentation, release of cytochrome c into the cytosol, and increasing of caspase-3 activity. It has also been found that LTC is an effective inhibitor of NF-kappaB, which suggests that leptocarpin induced cytotoxicity involves in some degree the inhibition of NF-kappaB signaling pathway. The concentration at which LTC inhibits NF-kappaB activity to the control level is similar or even lower than that found for parthenolide and others sesquiterpene lactones. These results indicate that leptocarpine is a very interesting molecule that could be considered as therapeutic agent for cancer treatment. PMID- 26562780 TI - Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database. AB - AIMS: There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear. METHODS: The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting <=2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality. RESULTS: The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51-0.99; P = 0.043). CONCLUSIONS: Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients. PMID- 26562781 TI - Insights into the adsorption capacity and breakthrough properties of a synthetic zeolite against a mixture of various sulfur species at low ppb levels. AB - The sorptive removal properties of a synthetic A4 zeolite were evaluated against sulfur dioxide (SO2) and four reference reduced sulfur compounds (RSC: hydrogen sulfide (H2S), methanethiol (CH3SH), dimethyl sulfide (DMS, (CH3)2S), and dimethyl disulfide (DMDS, CH3SSCH3). To this end, a sorbent bed of untreated (as received) A4 zeolite was loaded with gaseous standards at four concentration levels (10-100 part-per-billion (ppb (v/v)) at four different volumes (0.1, 0.2, 0.5, and 1 L increments) in both increasing (IO: 0.1-1.0 L) and decreasing volume order (DO: 1.0 to 0.1 L). Morphological properties were characterized by PXRD, FTIR, and BET analysis. The removal efficiency of SO2 decreased from 100% for all concentrations at 0.1 L (initial sample volume) to ~82% (100 ppb) or ~96% (10 ppb) at 3.6 L. In contrast, removal efficiency of RSC was near 100% at small loading volumes but then fell sharply, irrespective of concentration (10-100 ppb) (e.g., 32% (DMS) to 52% (H2S) at 100 ppb). The adsorption capacity of zeolite, if expressed in terms of solid-gas partition coefficient (e.g., similar to the Henry's law constant (mmol kg(-1) Pa(-1))), showed moderate variabilities with the standard concentration levels and S compound types such as the minimum of 2.03 for CH3SH (at 20 ppb) to the maximum of 13.9 for SO2 (at 10 ppb). It clearly demonstrated a notable distinction in the removal efficiency of A4 zeolite among the different S species in a mixture with enhanced removal efficiency of SO2 compared to the RSCs. PMID- 26562782 TI - Organization of cholinergic, catecholaminergic, serotonergic and orexinergic nuclei in three strepsirrhine primates: Galago demidoff, Perodicticus potto and Lemur catta. AB - The nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of three species of strepsirrhine primates is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of simian primates, megachiropterans and other mammalian species. The brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The nuclei identified were identical among the strepsirrhine species investigated and identical to previous reports in simian primates. Moreover, a general similarity to other mammals was found, but specific differences in the nuclear complement highlighted potential phylogenetic interrelationships. The central feature of interest was the structure of the locus coeruleus complex in the primates, where a central compactly packed core (A6c) of tyrosine hydroxylase immunopositive neurons was surrounded by a shell of less densely packed (A6d) tyrosine hydroxylase immunopositive neurons. This combination of compact and diffuse divisions of the locus coeruleus complex is only found in primates and megachiropterans of all the mammalian species studied to date. This neural character, along with variances in a range of other neural characters, supports the phylogenetic grouping of primates with megachiropterans as a sister group. PMID- 26562783 TI - Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease. AB - Tyrosine hydroxylase (TH, the rate limiting-enzyme in catecholamine synthesis) is regulated acutely via phosphorylation of 3 serine residues--Ser19, 31 and 40, and chronically via changes in TH protein levels. In this study, we aimed to investigate how TH is regulated in the brain, gut and adrenal gland as well as changes in mature brain-derived neurotrophic factor (mBDNF) and proBDNF levels in a low-dose (2 mg/kg, 5 days/week for 4 weeks) rotenone model of Parkinson's disease (PD). Rearing behaviour decreased by week 3 in the rotenone group (p<0.01), with further decreases in rearing by week 4 (p<0.001); however, TH remained unchanged in the substantia nigra (SN) and striatum; TH levels were also unaltered in other catecholaminergic cell groups of the brainstem such as A1C1 neurons or locus coeruleus. In the olfactory bulb, TH protein decreased (2.5 fold, p<0.01) while Ser31 phosphorylation increased (1.4-fold, p<0.05) in the rotenone group. In contrast, TH protein was increased in the adrenal gland (2 fold, p<0.05) and colon (5-fold, p<0.05) of rotenone rats. mBDNF levels were not changed in the SN but were significantly reduced in plasma and significantly increased in the colon (2-fold, p<0.01) of rotenone-treated rats. This is the first study to assess TH and BDNF in the brain and periphery in the rotenone model before SN/striatum degeneration is evident. Together these results suggest that low-dose rotenone may have some potential to model the early stages of PD. PMID- 26562784 TI - Diffusion-Weighted MRI in the Assessment of Early Treatment Response in Patients with Squamous-Cell Carcinoma of the Head and Neck: Comparison with Morphological and PET/CT Findings. AB - OBJECTIVE: To evaluate changes in apparent diffusion coefficients (ADC) as measured by magnetic resonance imaging (MRI) before and after the treatment of primary tumors and cervical metastases in patients with squamous-cell carcinoma (SCC) of the head and neck, and to compare these values to the results of widely used morphological criteria and [18F]-FDG PET/CT findings. MATERIAL AND METHOD: This was a longitudinal, prospective, single-center nonrandomized trial involving patients with head and neck SCC treated with chemotherapy alone or in combination with radiotherapy. Imaging examinations ([18F]-FDG PET/CT and diffusion-weighted MRI) were performed on the same day, up to one day prior to the beginning of the first treatment cycle, and on the 14th day of the first chemotherapy cycle. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) morphological criteria, as well as PET Response Criteria in Solid Tumors (PERCIST) metabolic criteria. RESULTS: Seventy-five lesions were examined in 23 patients. Pre- and post treatment comparisons of data pertaining to all target lesions revealed reductions in tumor size and SUV, as well as increases in ADC values, all of which were statistically significant. The increase in ADC following treatment was significantly higher in patients classified as complete responders by both morphological criteria than that observed in any of the other patient groups of response. Patients with a complete metabolic response also showed greater increases in ADC values as compared to the remaining groups. CONCLUSION: The assessment of tumor response based on diffusion-weighted MRI showed an increase in the ADC of cervical lesions following treatment, which was corroborated by morphological and metabolic findings. Associations between changes in ADC values and treatment response categories using morphologic criteria and [18F]-FDG PET/CT were only identified in complete responders. PMID- 26562785 TI - Imaging Sites of Inhibition of Proteolysis in Pathomimetic Human Breast Cancer Cultures by Light-Activated Ruthenium Compound. AB - The cysteine protease cathepsin B has been causally linked to progression and metastasis of breast cancers. We demonstrate inhibition by a dipeptidyl nitrile inhibitor (compound 1) of cathepsin B activity and also of pericellular degradation of dye-quenched collagen IV by living breast cancer cells. To image, localize and quantify collagen IV degradation in real-time we used 3D pathomimetic breast cancer models designed to mimic the in vivo microenvironment of breast cancers. We further report the synthesis and characterization of a caged version of compound 1, [Ru(bpy)2(1)2](BF4)2 (compound 2), which can be photoactivated with visible light. Upon light activation, compound 2, like compound 1, inhibited cathepsin B activity and pericellular collagen IV degradation by the 3D pathomimetic models of living breast cancer cells, without causing toxicity. We suggest that caged inhibitor 2 is a prototype for cathepsin B inhibitors that can control both the site and timing of inhibition in cancer. PMID- 26562786 TI - Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus. AB - BACKGROUND: The recently developed Xpert(r) Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert(r) Ebola Assay on whole blood samples. METHODS AND FINDINGS: This study evaluated the assay's analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay, the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51-97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163-302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert(r) Ebola for inactivation of infectious virus reduced EBOV titer by >=6 logs. CONCLUSION: In summary, we found the Xpert(r) Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical. PMID- 26562788 TI - Validation of pedestrian throw equations by video footage of real life pedestrian/vehicle collisions. AB - A total of 11 real life vehicle/pedestrian collisions in 2012-2014 were captured by CCTV cameras/car cameras in Hong Kong. Some of the footage was recorded in HD format at 30 frames per second, enabling accurate determinations of impact speeds with pedestrians, exact points of impacts and final rest positions of pedestrians as well as kinematics of the collisions. The calculated impact speeds from footage analysis were used to validate the published empirical and semi-empirical pedestrian throw equations. The applicability of these equations to collisions on sloped carriageways was discussed. The presented results, including 6 forward projection trajectory cases, enrich the existing limited real life data from footage analysis for further validation of the published methodologies. PMID- 26562787 TI - Determinants of Default from Tuberculosis Treatment among Patients with Drug Susceptible Tuberculosis in Karachi, Pakistan: A Mixed Methods Study. AB - PURPOSE: Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. METHODS: In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. RESULTS: Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71), being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77) were associated with default. CONCLUSIONS: In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment. PMID- 26562789 TI - Child homicide victims in forensic autopsy in Taiwan: A 10-year retrospective study. AB - BACKGROUND: Child homicides are critical medico-legal issues worldwide. Data on the characteristics of these cases in Asia are limited. This study aimed to describe the characteristics of child homicides in Taiwan. METHODS: A retrospective analysis of forensic autopsy records of child homicide victims (aged 0-17 years) in Taiwan, during a 10-year period between 2001 and 2010, was carried out. The age, sex, relationship with the perpetrator(s), injury patterns of the victims, and causes of death were analyzed. RESULTS: In all, 193 child homicide autopsies were identified. There were 38 (19.7%), 82 (42.5%), 25 (13.0%), and 48 (24.9%) homicide victims aged under 1, 1-5, 6-12, and 13-17 years, respectively. One-hundred boys (mean age: 8.4+/-7.0) and 93 girls (mean age: 3.7+/-4.3) were included. A female predominance was noted among the victims aged 0-5. Blunt force (53.4%) was the most frequent method of injury, followed by suffocation/strangulation (20.2%) and sharp force (13.0%). Bruise (64.8%) and brain injury (45.1%) were the most common types of injuries. The cranium (62.2%) and face (60.6%) were the most frequently injured body regions. The distribution of fatal injuries varied among victims in different age groups. Neurogenic shock, asphyxia, and hemorrhagic shocks were most common in victims aged 0-5, 6-12, and 13-17, respectively. The most frequent causes of death included blunt force head injury (40.4%), suffocation/strangulation (20.2%), and sharp force lung trauma (7.3%). The type of offenders, injury methods, types of injuries, distribution of injuries, mechanism of death, and causes of death were significantly different among victims of different age groups. Eighteen (9.33%) victims displayed no external evidence of trauma. CONCLUSIONS: The patterns of injuries, mechanism of death, and causes of death were different among victims of different age groups. A female predominance was noted among the victims aged 0-5. Complete forensic autopsy is necessary to identify child homicide. This report will help forensic examiners and forensic pathologists recognize the signs of child homicide and serve as a working basis for these professionals. PMID- 26562790 TI - Cryptosporidium Lactate Dehydrogenase Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Target for Developing Therapeutics. AB - The apicomplexan, Cryptosporidium parvum, possesses a bacterial-type lactate dehydrogenase (CpLDH). This is considered to be an essential enzyme, as this parasite lacks the Krebs cycle and cytochrome-based respiration, and mainly-if not solely, relies on glycolysis to produce ATP. Here, we provide evidence that in extracellular parasites (e.g., sporozoites and merozoites), CpLDH is localized in the cytosol. However, it becomes associated with the parasitophorous vacuole membrane (PVM) during the intracellular developmental stages, suggesting involvement of the PVM in parasite energy metabolism. We characterized the biochemical features of CpLDH and observed that, at lower micromolar levels, the LDH inhibitors gossypol and FX11 could inhibit both CpLDH activity (Ki = 14.8 MUM and 55.6 MUM, respectively), as well as parasite growth in vitro (IC50 = 11.8 MUM and 39.5 MUM, respectively). These observations not only reveal a new function for the poorly understood PVM structure in hosting the intracellular development of C. parvum, but also suggest LDH as a potential target for developing therapeutics against this opportunistic pathogen, for which fully effective treatments are not yet available. PMID- 26562791 TI - Diverse mechanisms for inflammasome sensing of cytosolic bacteria and bacterial virulence. AB - The inflammasomes are emerging cytosolic defenses against bacterial infections. The inflammasomes converge on inflammatory caspases activation that triggers pyroptosis, and interleukin-1beta/18 maturation in the case of caspase-1 activation. The inflammasomes not only detect major bacterial molecules but also sense bacterial virulence activity. Among the canonical caspase-1-activating inflammasomes, the NAIP subfamily of NLR proteins serves as the receptors for bacterial flagellin and type III secretion apparatus; Pyrin indirectly senses Rho modification/inactivation by various bacterial agents; NLRP1 in mice/rats detects the protease activity of anthrax lethal toxin by serving as its substrate. Caspase-11 and caspase-4/5 directly recognize bacterial LPS and then become activated. Inflammasome sensing of cytosolic bacteria employs much more diversified biochemical mechanisms, compared with Toll-like receptors-mediated recognition on the membrane. PMID- 26562792 TI - Effects of pineapple byproduct and canola oil as fat replacers on physicochemical and sensory qualities of low-fat beef burger. AB - Pineapple byproduct and canola oil were evaluated as fat replacers on physicochemical and sensory characteristics of low-fat burgers. Five treatments were performed: conventional (CN, 20% fat) and four low-fat formulations (10% fat): control (CT), pineapple byproduct (PA), canola oil (CO), pineapple byproduct and canola oil (PC). Higher water and fat retention and lower cooking loss and diameter reduction were found in burgers with byproduct addition. In raw burgers, byproduct incorporation reduced L*, a*, and C* values, but these alterations were masked after cooking, leading to products similar to CN. Low-fat treatments were harder, chewier, and more cohesive than full-fat burgers. However, in Warner Bratzler shear measurements, PA and PC were as tender as CN. In QDA, no difference was found between CN and PC. Pineapple byproducts along with canola oil are promising fat replacers in beef burgers. In order to increase the feasibility of use of pineapple byproduct in the meat industry, alternative processes of byproduct preparation should be evaluated in future studies. PMID- 26562793 TI - Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population. AB - BACKGROUND: It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). AIM: The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. METHODS: A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. RESULTS: The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). CONCLUSIONS: We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends. PMID- 26562794 TI - Spatial attention and reading ability: ERP correlates of flanker and cue-size effects in good and poor adult phonological decoders. AB - To investigate facilitatory and inhibitory processes during selective attention among adults with good (n=17) and poor (n=14) phonological decoding skills, a go/nogo flanker task was completed while EEG was recorded. Participants responded to a middle target letter flanked by compatible or incompatible flankers. The target was surrounded by a small or large circular cue which was presented simultaneously or 500ms prior. Poor decoders showed a greater RT cost for incompatible stimuli preceded by large cues and less RT benefit for compatible stimuli. Poor decoders also showed reduced modulation of ERPs by cue-size at left hemisphere posterior sites (N1) and by flanker compatibility at right hemisphere posterior sites (N1) and frontal sites (N2), consistent with processing differences in fronto-parietal attention networks. These findings have potential implications for understanding the relationship between spatial attention and phonological decoding in dyslexia. PMID- 26562795 TI - Cue Recognition and Integration - Eye Tracking Evidence of Processing Differences in Sentence Comprehension in Aphasia. AB - PURPOSE: We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations. METHODS: A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed. RESULTS: Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues. CONCLUSION: Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing delayed and therefore impaired recognition and integration of cues, as well as increased competition between interpretations. PMID- 26562796 TI - Augmentation of protein-derived acetic acid production by heat-alkaline-induced changes in protein structure and conformation. AB - Waste-derived acetic acid (HAc) is an attractive feedstock for microbe-mediated biofuel production. However, fermentative conversion of HAc from waste-activated sludge (WAS) has low yield because of the high concentration of proteins not readily utilizable by microorganisms without prior hydrolysis. We investigated a combined technology for HAc augmentation during sludge protein fermentation. The maximal HAc yield increased over two-fold, reaching 0.502 +/- 0.021 g/g protein (0.36 +/- 0.01 g COD/g COD, ~52% of the total volatile fatty acids) when synthetic sludge protein was heated at 120 degrees C for 30 min, treated at pH 12 for 24 h, and fermented at pH 9 for 72 h. Comprehensive analysis illustrated that the heat-alkaline pretreatment significantly induced protein fragmentation, simultaneously increasing the efficiency of protein biohydrolysis (from 35.5% to 85.9%) by inducing conformational changes indicative of protein unfolding. Consequently, the native alpha-helix content was decreased from 67.3% to 32.5% by conversion to an unordered shape, whose content increased from 27.5% to 45.5%; disulfide bonds were cleaved, whereas the main S-S stretching pattern was altered from gauche-gauche-gauche to gauche-gauche-trans, consequently causing increased protein susceptibility to proteolytic hydrolysis (76.3% vs. 47.0%). Economic analysis indicated that anaerobic fermentation with appropriate heat-alkaline pretreatment is a cost-effective approach for waste conversion to energy sources such as HAc. PMID- 26562797 TI - Nutrient removal, microalgal biomass growth, harvesting and lipid yield in response to centrate wastewater loadings. AB - The effects of wastewater, with four different nutrient loadings, from synthetic centrate on biomass production, nutrient removal, microalgal settling, and lipid production were investigated in photobioreactors under both batch and, subsequently, semi-continuous operations. At higher centrate concentration factors (17.2% and 36.2%), hydraulic retention time and pH adjustments could be employed to sustain acceptable microalgal growth rates and wastewater treatment. Similar nutrient removals efficiencies (>95%) and biomass production (0.42-0.51 g/L) were observed for the four centrate concentrations. Both the lipid productivity and lipid content decreased with increasing nutrient loading in the wastewater. The results also demonstrated that the mass ratio of carbohydrate to protein could provide a good indication of microalgal settling performance, rather than sole component composition or total extracellular polymeric substances. The highest settling efficiency (42.3 +/- 0.04% after 24 h) and lowest lipid content (10.2 +/- 1.6%) were observed for the lowest mass ratio of carbohydrate to protein (0.74 +/- 0.15) noted in the microalgae cultivated in the wastewater with the highest centrate concentration factor (36.2%). PMID- 26562798 TI - Utility of Helicobacter spp. associated GFD markers for detecting avian fecal pollution in natural waters of two continents. AB - Avian fecal droppings may negatively impact environmental water quality due to the presence of high concentrations of fecal indicator bacteria (FIB) and zoonotic pathogens. This study was aimed at evaluating the performance characteristics and utility of a Helicobacter spp. associated GFD marker by screening 265 fecal and wastewater samples from a range of avian and non-avian host groups from two continents (Brisbane, Australia and Florida, USA). The host prevalence and -specificity of this marker among fecal and wastewater samples tested from Brisbane were 0.58 and 0.94 (maximum value of 1.00). These values for the Florida fecal samples were 0.30 (host-prevalence) and 1.00 (host specificity). The concentrations of the GFD markers in avian and non-avian fecal nucleic acid samples were measured at a test concentration of 10 ng of nucleic acid at Brisbane and Florida laboratories using the quantitative PCR (qPCR) assay. The mean concentrations of the GFD marker in avian fecal nucleic acid samples (5.2 * 10(3) gene copies) were two orders of magnitude higher than non avian fecal nucleic acid samples (8.6 * 10(1) gene copies). The utility of this marker was evaluated by testing water samples from the Brisbane River, Brisbane and a freshwater creek in Florida. Among the 18 water samples tested from the Brisbane River, 83% (n = 18) were positive for the GFD marker, and the concentrations ranged from 6.0 * 10(1)-3.2 * 10(2) gene copies per 100 mL water. In all, 92% (n = 25) water samples from the freshwater creek in Florida were also positive for the GFD marker with concentrations ranging from 2.8 * 10(1)-1.3 * 10(4) gene copies per 100 mL water. Based on the results, it can be concluded that the GFD marker is highly specific to avian host groups, and could be used as a reliable marker to detect the presence and amount of avian fecal pollution in environmental waters. PMID- 26562799 TI - A multi-stable isotope framework to understand eutrophication in aquatic ecosystems. AB - Eutrophication is a globally significant challenge facing aquatic ecosystems, associated with human induced enrichment of these ecosystems with nitrogen (N) and phosphorus (P). However, the limited availability of inherent labels for P and N has constrained understanding of the triggers for eutrophication in natural ecosystems and appropriate targeting of management responses. This paper proposes and evaluates a new multi-stable isotope framework that offers inherent labels to track biogeochemical reactions governing both P and N in natural ecosystems. The framework couples highly novel analysis of the oxygen isotope composition of phosphate (delta(18)OPO4) with dual isotope analysis of oxygen and N within nitrate (delta(15)NNO3, delta(18)ONO3) and with stable N isotope analysis in ammonium (delta(15)NNH4). The River Beult in England is used as an exemplar system for initial evaluation of this framework. Our data demonstrate the potential to use stable isotope labels to track the input and downstream fate of nutrients from point sources, on the basis of isotopic differentiation for both P and N between river water and waste water treatment work effluent (mean difference = +1.70/00 for delta(18)OPO4; +15.50/00 for delta(15)NNH4 (under high flow); +7.30/00 for delta(18)ONO3 and +4.40/00 for delta(15)NNO3). Stable isotope data reveal nutrient inputs to the river upstream of the waste water treatment works that are consistent with partially denitrified sewage or livestock sources of nitrate (delta(15)NNO3 range = +11.5 to +13.10/00) and with agricultural sources of phosphate (delta(18)OPO4 range = +16.6 to +19.00/00). The importance of abiotic and metabolic processes for the in-river fate of N and P are also explored through the stable isotope framework. Microbial uptake of ammonium to meet metabolic demand for N is suggested by substantial enrichment of delta(15)NNH4 (by 10.20/00 over a 100 m reach) under summer low flow conditions. Whilst the concentration of both nitrate and phosphate decreased substantially along the same reach, the stable isotope composition of these ions did not vary significantly, indicating that concentration changes are likely driven by abiotic processes of dilution or sorption. The in-river stable isotope composition and the concentration of P and N were also largely constant downstream of the waste water treatment works, indicating that effluent-derived nutrients were not strongly coupled to metabolism along this in-river transect. Combined with in situ and laboratory hydrochemical data, we believe that a multi-stable isotope framework represents a powerful approach for understanding and managing eutrophication in natural aquatic ecosystems. PMID- 26562800 TI - Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges. AB - We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15min, keeping rectal temperatures <41.0 degrees C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures-i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death. PMID- 26562801 TI - Extracellular matrix structure. AB - Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. PMID- 26562802 TI - Enrichment and purification of total flavonoids from Cortex Juglandis Mandshuricae extracts and their suppressive effect on carbon tetrachloride induced hepatic injury in Mice. AB - In the present work, a simple and efficient chromatographic separation method was developed for preparative separation and enrichment of total flavonoids (TFs) from Cortex Juglandis Mandshuricae (CJM) extracts and then the protective effect of TFs against CCl4-induced acute liver injury in mice was investigated. Enrichment and purification of TFs from CJM extracts were studied using six macroporous resins and HPD-750 resin was selected as the best resin according to its adsorption and desorption properties. The operating parameters of resin column chromatography were optimized. Under the optimal conditions, TFs from CJM with purity larger than 50% were produced and their antioxidant activity was further evaluated in vitro. The mice were orally administrated with the purified TFs for seven days and then given CCl4 (0.3%, 10mL/kg i.p.). The results showed that TFs of CJM significantly attenuated the activities of serum aspartate transaminase (AST) and alanine transaminase (ALT) compared with model group, as well as the relative liver weight. Histopathological observation also revealed that TFs reduced the incidence of liver lesions and improved hepatocyte abnormality. Moreover, oral administration of TFs significantly enhanced antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) and decreased the content of malondialdehyde (MDA). Histopathological and biochemical results elicited that TFs of CJM had significant hepatoprotective activity comparable to the standard silymarin. This is the first time to reveal the protective actions of the TFs from CJM against CCl4-induced liver damage in mice and this natural product should be developed as a new drug for treatment of live injury in future. PMID- 26562803 TI - Quantitative subcellular study of doxorubicin in MCF-7/Adr cells using liquid chromatography-tandem mass spectrometry. AB - A rapid, sensitive and selective high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the determination of doxorubicin in intracellular compartments using glibenclamide as internal standard (IS). MCF-7/Adr cancer cells (1*10(6)) were incubated with doxorubicin (8MUg/mL) for 0.5, 1, 2 and 4h and then subjected to sequential extraction of cytosolic, membrane/organelle, nuclear and cytoskeleton soluble protein. Samples were extracted using protein precipitation with methanol. Chromatographic separation was carried out on a C18 column with acetonitrile and 0.1% formic acid water as mobile phase and with gradient elution at a flow rate of 0.2mL/min. The method was linear over the range of 1-300ng/mL with a lower limit of quantification (LLOQ) of 1ng/mL. The distribution of doxorubicin in subcellular components of MCF-7/Adr cancer cells was mainly in nucleic protein fraction. PMID- 26562804 TI - Separation of vitexin-4"-O-glucoside and vitexin-2"-O-rhamnoside from hawthorn leaves extracts using macroporous resins. AB - Vitexin-4"-O-glucoside and vitexin-2"-O-rhamnoside are the major flavonoids of hawthorn leaves. In this work, the adsorption and desorption characteristics of vitexin-4"-O-glucoside and vitexin-2"-O-rhamnoside on seven macroporous resins were evaluated. Among the tested resins, the HPD-400 resin showed the best adsorption and desorption capacities. Adsorption isotherms were constructed for the HPD-400 resin and well fitted to Langmuir and Freundlich models. Dynamic adsorption and desorption tests were performed on column packed with the HPD-400 resin to optimize the chromatographic parameters. After one run treatment with the HPD-400 resin, the contents of vitexin-4"-O-glucoside and vitexin-2"-O rhamnoside in the product were increased 8.44-fold and 8.43-fold from 0.720% and 2.63% to 6.08% and 22.2% with recovery yields of 79.1% and 81.2%, respectively. These results show that the developed method is a promising basis for the large scale purification of vitexin-4"-O-glucoside and vitexin-2"-O-rhamnoside from hawthorn leaves and other plant materials. PMID- 26562805 TI - A versatile effect of chitosan-silver nanocomposite for surface plasmonic photocatalytic and antibacterial activity. AB - Chitosan-silver (CS-Ag) nanocomposite was green synthesised without the aid of any external chemical-reducing agents. The synthesised nanocomposite was characterised by UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), high-resolution transmission electron microscopy (HR-TEM) with selected area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and zeta potential analyser. The particle size of the synthesised CS-Ag nanocomposite was around 20 nm and was found to be thermally stable in comparison with pure chitosan. The prepared nanocomposite acts as a photocatalyst for dye decolourisation, with a maximum of 81% of methyl orange (MO) decolourisation that occurred under visible light irradiation. The kinetics was found to follow pseudo first-order according to Langmuir-Hinshelwood (L-H) model. The nanocomposite also proved to be an excellent antimicrobial agent against both Gram-positive and Gram negative bacteria, possessing a broad spectrum of antimicrobial activity. The zone of inhibition ranged between 16.000 +/- 1.000 and 19.333 +/- 1.155 (mm), proving its high susceptibility than chitosan itself. The minimum inhibitory concentration (MIC) values were from 8 to 64 MUg/mL, whereas the minimum bactericidal concentration (MBC) values ranged from 16 to 128 MUg/mL, with the highest antibacterial activity shown against Gram-positive Staphlococcus aureus. This report illustrates the eco-friendly approach for the reduction of silver using chitosan as a reducing agent, and its potential to dye decay and microbial contaminants. PMID- 26562806 TI - Excitation energy transfer and charge separation are affected in Arabidopsis thaliana mutants lacking light-harvesting chlorophyll a/b binding protein Lhcb3. AB - The composition of LHCII trimers as well as excitation energy transfer and charge separation in grana cores of Arabidopsis thaliana mutant lacking chlorophyll a/b binding protein Lhcb3 have been investigated and compared to those in wild-type plants. In grana cores of lhcb3 plants we observed increased amounts of Lhcb1 and Lhcb2 apoproteins per PSII core. The additional copies of Lhcb1 and Lhcb2 are expected to substitute for Lhcb3 in LHCII trimers M as well as in the LHCII "extra" pool, which was found to be modestly enlarged as a result of the absence of Lhcb3. Time-resolved fluorescence measurements reveal a deceleration of the fast phase of excitation dynamics in grana cores of the mutant by ~15 ps, whereas the average fluorescence lifetime is not significantly altered. Monte Carlo modeling predicts a slowing down of the mean hopping time and an increased stabilization of the primary charge separation in the mutant. Thus our data imply that absence of apoprotein Lhcb3 results in detectable differences in excitation energy transfer and charge separation. PMID- 26562807 TI - Effect of 5-ALA-mediated photodynamic therapy on mast cell and microvessels densities present in oral premalignant lesions induced in rats. AB - Acute inflammatory response after photodynamic therapy is frequently described, and increase on mast cell degranulation is also present during this process. The mast cell activation may improve angiogenesis, and this fact has been associated with progression of oral premalignant lesions (OPL). The aim of this study was to evaluate whether photodynamic therapy (PDT) increases mast cell density (MCD) and microvessels density (MVD) in 4-nitroquinoline-1-oxide(4NQO)-induced OPL in rats. 4NQO-induced OPL were treated or not with 5-ALA followed by laser irradiation (PDT group and 4NQO groups, respectively). Mast cells and CD34+ microvessels were counted. Both PDT and 4NQO groups had MCD and MVD that were higher than normal mucosa (p b 0.05). The 4NQO group had the lowest number of non-degranulated MCD in comparison to experimental periods of PDT (PDT 6 h - p=0.020; 24 h - p=0.016; 48 h - p=0.003; 72 h - p=0.033). Only in the PDT group did MCD and MVD have a significant correlation (r= 0.6219, p = 0.010). 5-ALA-mediated PDT modified the MCD and MVD in the induced OPL, leading to degranulation of mast cells and angiogenesis. A PDT protocol with an efficient eradication of the OPL must be adopted considering the angiogenesis potential associated with the mast cell activation after the therapy. PMID- 26562808 TI - Interactive effects of UV radiation and reduced precipitation on the seasonal leaf phenolic content/composition and the antioxidant activity of naturally growing Arbutus unedo plants. AB - The effects of UV radiation and rainfall reduction on the seasonal leaf phenolic content/composition and antioxidant activity of the Mediterranean shrub Arbutus unedo were studied. Naturally growing plants of A. unedo were submitted to 97% UV B reduction (UVA), 95% UV-A+UV-B reduction (UV0) or near-ambient UV levels (UVBA) under two precipitation regimes (natural rainfall or 10-30% rainfall reduction). Total phenol, flavonol and flavanol contents, levels of eight phenols and antioxidant activity [DPPH(?) radical scavenging and Cu (II) reducing capacity] were measured in sun-exposed leaves at the end of four consecutive seasons. Results showed a significant seasonal variation in the leaf content of phenols of A. unedo, with the lowest values found in spring and the highest in autumn and/or winter. Leaf ontogenetic development and/or a possible effect of low temperatures in autumn/winter may account for such findings. Regardless of the watering regime and the sampling date, plant exposure to UV-B radiation decreased the total flavanol content of leaves, while it increased the leaf content in quercitrin (the most abundant quercetin derivative identified). By contrast, UV-A radiation increased the leaf content of theogallin, a gallic acid derivative. Other phenolic compounds (two quercetin derivatives, one of them being avicularin, and one kaempferol derivative, juglanin), as well as the antioxidant activity of the leaves, showed different responses to UV radiation depending on the precipitation regime. Surprisingly, reduced rainfall significantly decreased the total amount of quantified quercetin derivatives as well as the DPPH scavenging activity in A. unedo leaves. To conclude, present findings indicate that leaves of A. unedo can be a good source of antioxidants throughout the year, but especially in autumn and winter. PMID- 26562809 TI - Kenyan MSM: no longer a hidden population. PMID- 26562810 TI - Changes in sexual risk behavior among MSM participating in a research cohort in coastal Kenya. AB - OBJECTIVE: To describe changes in sexual risk behavior among Kenyan MSM who received regular risk reduction counseling (RRC). DESIGN: Data were derived from two cohorts of HIV-1-negative and HIV-1-positive MSM in Kenya. Behavioral data were collected at enrollment and at monthly or quarterly scheduled follow-up visits. At each visit, RRC was provided to all men and HIV-1 testing to seronegative men. METHODS: Random effects logistic and Poisson regression models with time since study entry as main variable of interest were used to evaluate changes in number of sex partners and unprotected sex in the past week, and insertive, receptive, and unprotected anal intercourse in the past 3 months. Analyses were adjusted for HIV-1-status, calendar year of follow-up, and several baseline characteristics. Trends over follow-up time were allowed to differ by HIV-1-status. Men were censored when they seroconverted for HIV. RESULTS: Number of regular and casual sex partners and unprotected anal intercourse decreased in both HIV-1-negative and HIV-1-positive men. Unprotected sex with both regular and casual sex partners decreased more strongly early in follow-up in HIV-1-positive men than in HIV-1-negative men. Decreases in insertive anal intercourse were found for HIV-1-positive men only, whereas decreases in receptive anal intercourse were found for HIV-1-negative men only. CONCLUSION: MSM who were regularly exposed to RRC showed some reductions in sexual risk behavior, but it is uncertain if these reductions are sustained over time. As HIV-1 incidences in Kenyan MSM are very high, RRC should be supported by comprehensive biomedical interventions. PMID- 26562811 TI - Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa. AB - BACKGROUND: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission. METHODS: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site. RESULTS: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing. CONCLUSION: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI. PMID- 26562812 TI - Risk of sexual, physical and verbal assaults on men who have sex with men and female sex workers in coastal Kenya. AB - BACKGROUND: Violence toward MSM and female sex workers (FSW) is associated with HIV risk, and its prevention is prioritized in international HIV/AIDS policy. METHODS: Sociodemographic and behavioural data derived from HIV risk and follow up cohorts including MSM and FSW in coastal Kenya between 2005 and 2014 was used to estimate the risk of rape, physical assault and verbal abuse, and to assess associations between first occurrence of assault with individual and recent behavioural factors. RESULTS: Incidence of first reported rape was similar for MSM [3.9, confidence interval (CI) 3.1-5.0 per 100 person-years (pyrs)] and FSW (4.8 CI 3.5-6.4 per 100 pyrs), P = 0.22. Incidence of first reported physical and verbal assault was higher for FSW than MSM (21.1 versus 12.9 per 100 pyrs, P = 0.14 and 51.3 versus 30.9 per 100 pyrs, P = 0.03 respectively). Recent alcohol use was associated with reporting of all forms of assault by MSM [adjusted odds ratio (AOR) 1.8, CI 0.9-3.5] and FSW (AOR 4.4, CI 1.41-14.0), as was recent sale of sex for MSM (AOR 2.0, CI 1.1-3.8). Exclusive sex with men, active sex work, and group sex were also specifically associated with reporting rape for MSM. Perpetrators of sexual and verbal assault were usually unknown, whilst perpetrators of physical violence toward FSW were usually regular sexual partners. CONCLUSION: MSM and FSW experienced a similarly high incidence of sexual assault in coastal Kenya, in addition to physical and verbal assault. Current national policies focus heavily on gender-based violence against women and young girls, but need to be inclusive of MSM and FSW. PMID- 26562813 TI - Development and pilot testing of an intervention to promote care engagement and adherence among HIV-positive Kenyan MSM. AB - OBJECTIVES: In many African settings, MSM are a stigmatized group whose access to and engagement in HIV care may be challenging. Our aim was to design a targeted, culturally appropriate intervention to promote care engagement and antiretroviral therapy (ART) adherence for MSM in coastal Kenya, and describe intervention safety, feasibility, and acceptability based upon a small pilot study. DESIGN: Based on qualitative work including in-depth interviews with HIV-positive MSM and focus groups with providers, we developed a tailored intervention and conducted a pilot test to refine intervention materials and procedures. METHODS: The Shikamana intervention combines modified Next-Step Counseling by trained providers, support from a trained peer navigator, and tailored use of SMS messaging, phone calls, and discrete pill carriers. Providers, including counselors and clinicians, work together with peer navigators as a case management team. RESULTS: Forty HIV-positive MSM aged 19-51 participated in intervention development and testing. Six counselors, three clinical officers, and four MSM peers were trained in intervention procedures. Of 10 ART-naive participants who enrolled in the pilot, eight completed follow-up with no adverse events reported. One participant was lost to follow-up after 2 months and another failed to initiate ART despite ongoing counseling. No adverse events were reported. Staff feedback and exit interviews rated the intervention as feasible and acceptable. CONCLUSION: This adherence support intervention tailored for Kenyan MSM was well tolerated, feasible, and acceptable in the pilot phase. A randomized controlled trial of a scaled-up programme to estimate intervention efficacy is ongoing. PMID- 26562815 TI - Resilience among gay/bisexual young men in Western Kenya: psychosocial and sexual health outcomes. AB - OBJECTIVE: To explore associations between intrapersonal and interpersonal factors and both sexual and psychosocial resilient outcomes among young gay, bisexual, and other men who have sex with men (GBMSM) in Western Kenya. DESIGN: Cross-sectional observational study. METHODS: Five hundred and eleven GBMSM ages 18-29 were recruited from nine communities in Western Kenya using community-based mobilization strategies. Participants completed an audio computer-assisted self interview survey in English or Duhluo. We estimated four three-step hierarchical linear regression models to examine associations between predictors (intrapersonal and interpersonal factors) and four resilient outcomes (psychological well-being, self-esteem, condom use, HIV testing). RESULTS: Psychosocial well-being model (modeled conversely as depression/anxiety) was significant (F(13,424) = 106.41, P < 0.001, R = 0.765) with loneliness, lesbian/gay/bisexual (LGB) difficult process, LGB identity superiority, and reactions to trauma as predictors. Self-esteem model was significant (F(12,425) = 6.40, P < 0.001, R = 0.153) with known HIV-seropositivity, perceived social support, internalized homonegativity, and LGB difficult process as predictors. Condom use model was significant (F(13,379) = 4.30, P < 0.001, R = 0.128) with perceived social support, self-esteem, and reactions to trauma as predictors. HIV testing model was significant (F(12,377) = 4.75, P < 0.001, R = 0.131) with loneliness, LGB identity uncertainty, LGB difficult process, and LGB identity superiority as predictors. CONCLUSION: This study demonstrates the variety of ways in which intrapersonal and interpersonal factors are associated with HIV related resilient outcomes for young GBMSM in Western Kenya. HIV prevention programs for this population should be developed in collaboration with GBMSM and include intervention components that promote resilience. PMID- 26562814 TI - Depression, substance abuse and stigma among men who have sex with men in coastal Kenya. AB - OBJECTIVES: Mental health conditions can erode quality of life and interfere with health-related behaviours such as medication adherence. We aimed to determine the prevalence and correlates of depression and other psychosocial factors among self identified men who have sex with men (MSM) in coastal Kenya. DESIGN: A cross sectional survey. METHODS: Psychosocial and mental health characteristics were assessed in an audio computer-assisted self-interview (ACASI) survey among 112 MSM participating in two ongoing HIV-positive and HIV-negative cohorts in Mtwapa, Kenya. RESULTS: One-third of participants met criteria for major depressive disorder [16.1%, 95% confidence interval (95% CI) 9.8-24.2] or other depressive disorder (15.2%, 95% CI 9.1-23.2). Alcohol abuse was reported by 45% of respondents (95% CI 35.2-54.3) and other substance abuse by 59.8% (95% CI 50.1 69.0). Sexual and HIV stigma were moderate, with median scores of 11 [interquartile range (IQR) 6-17, potential range 0-33] and 25 (IQR 23-29, potential range 11-44), respectively. There were significant bivariate correlations between alcohol abuse, other substance abuse, sexual stigma and childhood and recent abuse. In a multivariable linear regression model, sexual stigma (beta = 0.17, 95% CI 0.03-0.32) and marriage to a woman (beta = -2.41 95% CI -4.74 to -0.09) were each associated with depression score. CONCLUSION: We found moderate to high levels of depression and substance abuse, and moderate levels of sexual stigma. These variables were highly inter-correlated and associated with an experience of trauma or abuse. Comprehensive mental health services are needed in this population to address these issues. PMID- 26562816 TI - Effects of Congenital Visual Deprivation on the Auditory Perception of Anticipatory Labial Coarticulation. AB - OBJECTIVE: It has been shown previously that congenitally blind francophone adults had higher auditory discrimination scores than sighted adults. It is unclear, however, if, compared to their sighted peers, blind speakers display an increased ability to detect anticipatory acoustic cues. In this paper, this ability is investigated in both speaker groups. METHODS: Using the gating paradigm, /izi/ and /izy/ sequences were truncated to include a variable duration of the vowel. The sequences were used as stimuli in an auditory identification test. Seventeen congenitally blind adults (9 females and 8 males) and 17 sighted controls were recruited. Their task was to identify the second vowel of the sequence. RESULTS: Results show that all participants could reliably identify the rounded vowel prior to its acoustic onset, but steeper identification slopes were found for sighted listeners than for blind listeners. CONCLUSION: The difference in identification slopes likely suggests that sighted speakers display finer abilities to perceptually follow the decreasing values of the frication noise, compared to blind speakers. PMID- 26562818 TI - Scanning Electron Microscopic Analysis of Biofilm Formation in Explanted Human Boston Type I Keratoprostheses. AB - PURPOSE: To describe the morphological distribution of host tissue and microbial biofilms on the intraocular surfaces of Boston type I keratoprostheses (KPros) explanted because of corneal melt. METHODS: Retrospective study of scanning electron microscopy (SEM) images from 4 explanted Boston type I KPros composed of polymethylmethacrylate and titanium. SEM images of KPro-associated ocular surfaces were reviewed for the presence of inflammatory cells, microbes, and/or biofilm formation. One sterile type I KPro was also imaged to serve as a (device only) control. RESULTS: All 4 KPros were explanted because of culture-negative, clinically "sterile" donor corneal melt with impending KPro extrusion. In all cases, the rough, irregular surfaces of the device harbored more adherent corneal epithelium and stromacytes, inflammatory cells, and bacteria than the smooth, polished surface of the KPro optic. Two KPros showed not only evidence of prior bacterial colonization but marked biofilm formation. CONCLUSIONS: SEM images of explanted KPros explanted for "sterile" corneal melt demonstrated evidence of biofilm formation despite negative donor corneal cultures and the absence of clinical suspicion for infection. These results suggest that "sterile" corneal melt may be due to inflammatory host responses to low microbial burdens as seen in biofilms and/or released antigens after antibiotic-induced lysis. There was increased adherence of host tissue cells and microbial biofilms on the nonpolished surfaces of the KPro. Polishing the intraocular polymethylmethacrylate and titanium KPro surfaces may decrease microbial adhesion and biofilm formation in human subjects with KPros, but what impact this will have on rates of postoperative endophthalmitis is unknown. PMID- 26562817 TI - Evaluation of Vancomycin Use in Late-Onset Neonatal Sepsis Using the Area Under the Concentration-Time Curve to the Minimum Inhibitory Concentration >=400 Target. AB - AIM: To develop a vancomycin population pharmacokinetic model and assess the probability of attaining a pharmacodynamic target associated with clinical and microbiological success, a ratio of the 24-hour area under the concentration-time curve to the minimum inhibitory concentration (MIC) >= 400, in a 5-year clinical cohort of preterm and term neonatal patients with late-onset staphylococcal sepsis. METHODS: Therapeutic drug monitoring data were obtained from septic neonates with >=1 vancomycin concentration(s) from January 2006 to September 2011. Only neonates with a postnatal age of >72 hours and a positive microbiological culture were included. Population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM 7.2). Eleven demographic characteristics were evaluated as covariates. Probabilities of achieving the pharmacodynamic target were evaluated. RESULTS: A 1-compartment model with first order elimination was constructed from 528 vancomycin concentrations collected from 152 preterm and term neonates. Body weight, creatinine clearance (CL), and postmenstrual age were identified as significant covariates. Estimated vancomycin CL and volume of distribution for typical neonates were 0.068 +/- 0.03 L.h.kg and 0.62 +/- 0.13 L/kg, respectively. Coagulase-negative staphylococci (85.5%) and Staphylococcus aureus (14.5%) were the common pathogenic organisms. The distribution of vancomycin MIC breakpoints was composed of approximately 70% MIC breakpoint of <=2 mcg/mL. Approximately 54% of neonates, with a median serum creatinine concentration of 0.44 mg/dL, achieved the target ratio of 24-hour area under the concentration-time curve to the MIC >= 400 with a median daily dose of 30 (interquartile range, 21-42) mg/kg. CONCLUSIONS: Body weight, creatinine CL, and postmenstrual age significantly influenced vancomycin CL. The current vancomycin doses are acceptable at MICs <=1 mcg/mL because they are likely to achieve the pharmacodynamic target in the majority of neonatal patients, although higher doses may be considered for more resistant staphylococcal infections. PMID- 26562819 TI - Early Deep Anterior Lamellar Keratoplasty (DALK) for Acanthamoeba Keratitis Poorly Responsive to Medical Treatment. AB - PURPOSE: To evaluate the success (eradication of infection) or failure (recurrence of infection in the cornea or sclera, or endophthalmitis) of early therapeutic deep anterior lamellar keratoplasty (DALK) for active Acanthamoeba keratitis (AK) poorly responsive to medical treatment. METHODS: Retrospective, noncomparative case series of 11 patients (11 eyes) affected by active AK poorly responsive to medical treatment who underwent early therapeutic DALK. Surgery was performed in all cases within 30 to 60 days from the onset of symptoms. Corneal ulcer depth was less than 300 MUm in all cases. A 3-drug combination (chlorhexidine gluconate, propamidine isethionate, and neomycin sulfate) was the antiamoebic protocol used preoperatively and postoperatively. Cannula big bubble and "layer-by-layer" manual dissection techniques were performed. Eradication of infection, episodes of rejection, postoperative endothelial cell density, and the best spectacle-corrected visual acuity were evaluated. Histologic examination of surgical margins was performed, and margin clearance was assessed. Mean follow-up was approximately 2 years. RESULTS: Four descemetic DALK and 7 predescemetic DALK were performed. One small Descemet membrane rupture occurred. Peripheral surgical margins were free of infection in all cases. Deep surgical margins not free from infection were found in 2 cases. However, no episode of infection recurrence was observed. The postoperative average best spectacle-corrected visual acuity was 0.8 (range, 0.6-1.0). No case of rejection was recorded. CONCLUSIONS: Early therapeutic DALK could be considered a new approach to eradicate active infection in AK cases poorly responsive to medical treatment, with significant ulcer in the optical zone. Further studies are needed to validate this new indication for DALK. PMID- 26562821 TI - Causes and Timing of Unplanned Early Readmission After Neurosurgery. AB - BACKGROUND: Reducing the rate of 30-day hospital readmission has become a priority in healthcare quality improvement policy, with a focus on better characterizing the reasons for unplanned readmission. In neurosurgery, however, peer-reviewed analyses describing the patterns of readmission have been limited in their number and generalizability. OBJECTIVE: To determine the incidence, timing, and causes of 30-day readmission after neurosurgical procedures. METHODS: We conducted a retrospective longitudinal study from 2009 to 2012 using the Statewide Planning And Research Cooperative System, which collects patient-level details for all admissions and discharges within New York. We identified patients readmitted within 30 days of initial discharge. The rate of, reasons for, and time to readmission were determined overall and within 4 subgroups: craniotomies, cranial surgery without craniotomy, spine, and neuroendovascular procedures. RESULTS: There were 163 743 index admissions, of whom 14 791 (9.03%) were readmitted. The most common reasons for unplanned readmission were infection (29.52%) and medical complications (19.22%). Median time to readmission was 11 days, with hemorrhagic strokes and seizures occurring earlier, and medical complications and infections occurring later. Readmission rates were highest among patients undergoing cerebrospinal fluid shunt revision and malignant tumor resection (15.57%-22.60%). Spinal decompressions, however, accounted for the largest volume of readmissions (33.13%). CONCLUSION: Many readmissions may be preventable and occur at predictable time intervals. The causes and timing of readmission vary significantly across neurosurgical subgroups. Future studies should focus on detecting specific complications in select cohorts at predefined time points, which may allow for interventions to lower costs and reduce patient morbidity. ABBREVIATIONS: CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System. PMID- 26562823 TI - Early Moderate Hyperoxemia Does Not Predict Outcome After Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Targeting hyperoxemia is common practice in neurocritical care settings, but the safety of hyperoxemia has been questioned. OBJECTIVE: To investigate the independent effect of hyperoxemia on outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: We included 432 patients with aneurysmal SAH on mechanical ventilation for at least 24 hours after intensive care unit (ICU) admission. Arterial blood gas levels were calculated as time weighted averages (TWAs) of all blood gas measurements during the first 24 hours in the ICU. Patients were categorized into 3 TWA-PaO2 bands (low, <97.5 mm Hg; intermediate, 97.5-150 mm Hg; high, >=150 mm Hg). Outcome measures were unfavorable outcome at 3 months (Glasgow Outcome Scale score 1-3) and mortality. Multivariate logistic regression analysis was used to assess the independent effect of oxygen on outcome. RESULTS: Overall, 28% of patients died, and a total of 53% had an unfavorable outcome at 3 months. Patients with an unfavorable outcome had significantly higher TWA-PaO2 levels compared with patients with a favorable outcome (137 mm Hg vs 118 mm Hg, P < .001). Multivariate analysis demonstrated no significant association between TWA-PaO2 bands and unfavorable outcome (with intermediate PaO2 as a reference, odds ratio [OR] for low PaO2 1.05, 95% confidence interval [CI]: 0.52-2.12, P = .89; OR for high PaO2: 1.09, 95% CI: 0.61-1.97, P = .77) or mortality (with intermediate PaO2 as reference, the OR for low PaO2 was 0.67 (95% CI: 0.30-1.46, P = .31), and the OR for high PaO2 was 0.73 (95% CI: 0.38-1.40, P = .34). CONCLUSION: Early moderate hyperoxemia may not increase or decrease the risk of a poor outcome in mechanically ventilated aneurysmal SAH patients. PMID- 26562824 TI - Complication-Effectiveness Analysis for Unruptured Intracranial Aneurysm Surgery: A Prospective Cohort Study. AB - BACKGROUND: The aim of intervention for unruptured intracranial aneurysms (UIAs) is safe, effective treatment. OBJECTIVE: To analyze a prospective database for variables influencing the risk of surgery to produce a risk model adjusting this risk for effectively treated aneurysms. METHODS: First, we identified variables to create a model from multiple logistic regression for complications of surgery leading to a 12-month modified Rankin Scale score >1. Second, we established the long-term cumulative incidence of freedom from retreatment or rupture (treated aneurysm) from Kaplan-Meier analysis. Third, we combined these analyses to establish a model of risk of surgery per effective treatment. RESULTS: One thousand twelve patients with 1440 UIA underwent 1080 craniotomies. We found that 10.1% (95% confidence interval [CI], 8.4-12.0) of craniotomies resulted in a complication leading to a modified Rankin Scale score >1 at 12 months. Logistic regression found age (odds ratio, 1.04; 95% CI, 1.02-1.06), size (odds ratio, 1.12; 95% CI, 1.09-1.15), and posterior circulation location (odds ratio, 2.95; 95% CI, 1.82-4.78) to be significant. Cumulative 10-year risk of retreatment or rupture was 3.0% (95% CI, 1.3-7.0). The complication-effectiveness model was derived by dividing the complication risk by the 10-year cumulative freedom from retreatment or rupture proportion. Risk per effective treatment ranged from 1% for a 5-mm anterior circulation UIA in a 20-year-old patient to 70% for a giant posterior circulation UIA in a 70-year-old patient. CONCLUSION: Complication effectiveness analyses increase the information available with regard to outcome for the management of UIAs. PMID- 26562826 TI - Impact of screening mammography on breast cancer mortality. AB - The degree to which observed reductions in breast cancer mortality is attributable to screening mammography has become increasingly controversial. We examined this issue with three fundamentally different approaches: (i) Chronology -the temporal relationship of the onset of breast cancer mortality decline and the national implementation of screening mammography; (ii) Magnitude--the degree to which breast cancer mortality declined relative to the amount (penetration) of screening mammography; (iii) Analogy--the pattern of mortality rate reductions of other cancers for which population screening is not conducted. Chronology and magnitude were assessed with data from Europe and North America, with three methods applied to magnitude. A comparison of eight countries in Europe and North America does not demonstrate a correlation between the penetration of national screening and either the chronology or magnitude of national breast cancer mortality reduction. In the United States, the magnitude of the mortality decline is greater in the unscreened, younger women than in the screened population and regional variation in the rate of breast cancer mortality reduction is not correlated with screening penetrance, either as self-reported or by the magnitude of screening-induced increase in early-stage disease. Analogy analysis of United States data identifies 14 other cancers with a similar distinct onset of mortality reduction for which screening is not performed. These five lines of evidence from three different approaches and additional observations discussed do not support the hypothesis that mammography screening is a primary reason for the breast cancer mortality reduction in Europe and North America. PMID- 26562827 TI - Multifocal motor neuropathy: 30 years from onset to diagnosis. PMID- 26562828 TI - Diagnostic accuracy of thyroid nodule growth to predict malignancy in thyroid nodules with benign cytology: systematic review and meta-analysis. AB - BACKGROUND: Thyroid ultrasound to assess for nodular growth is commonly performed during the follow-up of patients with benign thyroid nodules, with the goal of identifying patients with a missed diagnosis of thyroid cancer. The objective of this study was to summarize the evidence regarding the diagnostic accuracy of growth during follow-up of benign thyroid nodules for thyroid cancer. METHODS: We searched multiple electronic databases using a search strategy designed by an experienced medical librarian from inception to March 2015. Eligible studies included patients with benign thyroid nodules assessed for growth during follow up and evaluated for thyroid cancer either by surgical histology or a repeat fine needle aspiration biopsy. Reviewers working independently and in duplicate recorded data and assessed each study. RESULTS: The seven eligible studies lacked safeguards against bias and generated results that were imprecise with wide confidence intervals and inconsistent across studies. This warrants very low confidence in these results. The odds of nodule growth in patients with thyroid cancer on histopathology over these odds in patients without thyroid cancer (diagnostic odds ratio) was 0.58 (95% CI: 0.26-1.3); the diagnostic odds ratio was 2.2 (95% CI: 0.26-18) when an abnormal repeat biopsy was the reference standard. CONCLUSION: The body of evidence linking nodule growth with thyroid cancer during the follow-up of benign nodules warrants very low confidence. In the era of high-value health care, the commonplace practice of following benign thyroid nodules with serial ultrasound assessment of growth to diagnose cancer can be questioned, calling for imminent evaluation. PMID- 26562829 TI - Indoor inhalation intake fractions of fine particulate matter: review of influencing factors. AB - Exposure to fine particulate matter (PM2.5 ) is a major contributor to the global human disease burden. The indoor environment is of particular importance when considering the health effects associated with PM2.5 exposures because people spend the majority of their time indoors and PM2.5 exposures per unit mass emitted indoors are two to three orders of magnitude larger than exposures to outdoor emissions. Variability in indoor PM2.5 intake fraction (iFin,total ), which is defined as the integrated cumulative intake of PM2.5 per unit of emission, is driven by a combination of building-specific, human-specific, and pollutant-specific factors. Due to a limited availability of data characterizing these factors, however, indoor emissions and intake of PM2.5 are not commonly considered when evaluating the environmental performance of product life cycles. With the aim of addressing this barrier, a literature review was conducted and data characterizing factors influencing iFin,total were compiled. In addition to providing data for the calculation of iFin,total in various indoor environments and for a range of geographic regions, this paper discusses remaining limitations to the incorporation of PM2.5 -derived health impacts into life cycle assessments and makes recommendations regarding future research. PMID- 26562830 TI - Corrigendum: Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation mediated neuronal injury. PMID- 26562832 TI - Correction: Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons. PMID- 26562831 TI - Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes. AB - The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 +/- 0.13 * 10-8 mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes. PMID- 26562833 TI - Genomic Pathogen Typing Using Solid-State Nanopores. AB - In clinical settings, rapid and accurate characterization of pathogens is essential for effective treatment of patients; however, subtle genetic changes in pathogens which elude traditional phenotypic typing may confer dangerous pathogenic properties such as toxicity, antibiotic resistance, or virulence. Existing options for molecular typing techniques characterize the critical genomic changes that distinguish harmful and benign strains, yet the well established approaches, in particular those that rely on electrophoretic separation of nucleic acid fragments on a gel, have room for only incremental future improvements in speed, cost, and complexity. Solid-state nanopores are an emerging class of single-molecule sensors that can electrophoretically characterize charged biopolymers, and which offer significant advantages in terms of sample and reagent requirements, readout speed, parallelization, and automation. We present here the first application of nanopores for single molecule molecular typing using length based "fingerprints" of critical sites in bacterial genomes. This technique is highly adaptable for detection of different types of genetic variation; as we illustrate using prototypical examples including Mycobacterium tuberculosis and methicillin-resistant Streptococcus aureus, the solid-state nanopore diagnostic platform may be used to detect large insertions or deletions, small insertions or deletions, and even single nucleotide variations in bacterial DNA. We further show that Bayesian classification of test samples can provide highly confident pathogen typing results based on only a few tens of independent single-molecule events, making this method extremely sensitive and statistically robust. PMID- 26562834 TI - Histological and Ultrastructural Studies on the Conjunctiva of the Barred Owl (Strix varia). AB - This report is the first characterization of the histology and ultrastructure of the barred owl conjunctiva. The inferior eyelid was dominated by a large disk shaped plate covered by a non-keratinized stratified squamous or cuboidal epithelium of variable thickness. The apical surface of the plate epithelium varied from flat to long microvilli or even short cytoplasmic extensions similar to those seen in the third eyelid. All specimens had a few goblet cells filled with mucous secretory granules in the plate region. The underlying connective tissue was a dense fibroelastic stroma. Eosinophils were surprisingly common in the epithelial layer and underlying connective tissue in the plate and more distal orbital mucosal region. The orbital mucosa contained goblet cells with heterogeneous glycosylation patterns. The leading edge and marginal plait of the third eyelid are designed to collect fluid and particulate matter as they sweep across the surface of the eye. The palpebral conjunctival surface of the third eyelid was covered by an approximately five-cell-deep stratified squamous epithelium without goblet cells. The bulbar surface of the third eyelid was a bilayer of epithelial cells whose superficial cells have elaborate cytoplasmic tapering extensions reaching out 25 MUm. Narrow cytofilia radiated outwards up to an additional 15-20 MUm from the cytoplasmic extensions. Lectin labeling demonstrated heterogeneous glycosylation of the apical membrane specializations but only small amounts of glycoprotein-filled secretory granules in the third eyelid. PMID- 26562835 TI - Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord. AB - BACKGROUND: Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown. The aim of this study was to assess the effect of the subdural KYNA infusion on the spinal cord in adult rats. METHODS: A total of 42 healthy adult rats were randomly assigned into six groups and were infused for 7 days with PBS (control) or 0.0002 pmol/min, 0.01 nmol/min, 0.1 nmol/min, 1 nmol/min, and 10 nmol/min of KYNA per 7 days. The effect of KYNA on spinal cord was determined using histological and electron microscopy examination. Myelin oligodendrocyte glycoprotein (MOG) was measured in the blood serum to assess a degree of myelin damage. RESULT: In all rats continuous long lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia. CONCLUSIONS: We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role of KYNA in control of physiological myelination process. PMID- 26562837 TI - Prognostic Role of Adjuvant Chemotherapy in Node-Negative (N0), Triple-Negative (TN), Medullary Breast Cancer (MBC) in the Korean Population. AB - BACKGROUND: Despite the favorable prognosis for medullary breast cancer (MBC), the guidelines for the use of adjuvant chemotherapy for MBC have not been clearly established. This study investigated the prognostic role of adjuvant chemotherapy in Korean patients with node-negative (N0), triple-negative (TN) MBC patients. METHODS: We included data from 252 patients with N0 TN MBC, obtained from the Korean Breast Cancer Registry database. Patients were categorized as those who did not undergo adjuvant chemotherapy (group I) or those who did (group II). Clinicopathological characteristics, breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the groups. In addition, a subgroup analysis for survival based on tumor size was conducted. RESULTS: A total of 252 N0 TN MBC patients with tumor sizes >1 cm who were diagnosed between April 1997 and March 2011 were enrolled. The median age was 44.95 years (range, 25-72 years), and the median follow-up period was 93.94 months (range, 23-195 months). Overall, the BCSS and OS in group II (97.3% and 97.3%, respectively) were significantly better compared with those in group I (89.2% and 86.2%, respectively). In the subgroup analysis, in patients with tumors >2 cm in size, those in group II had significant better BCSS and OS (97.5% and 97.5%, respectively) compared with those in group I (78.3% and 73.9%, respectively). In contrast in those with tumors 1-2 cm in size, there were no significant differences in BCSS and OS between the groups (both 97.1% for group I, and 95.2% and 92.9%, respectively for group II). Multivariate analysis revealed that adjuvant chemotherapy significantly improved BCSS (P = 0.009) and OS (P = 0.007), but only for patients with larger tumors (>2 cm). CONCLUSIONS: In patients with N0 TN MBC, adjuvant chemotherapy had a significant clinical survival benefit, but only in those with tumors >2 cm. PMID- 26562836 TI - Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study. AB - New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as betaeta-2 microglobulin (beta2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54+/-14 years, serum creatinine 104 MUmol/l [IQR 90-113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3-11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy. PMID- 26562838 TI - Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses. AB - Several pathogens have been described to enter host cells via cholesterol enriched membrane lipid raft microdomains. We found that disruption of lipid rafts by the cholesterol-extracting agent methyl-beta-cyclodextrin or by the cholesterol-binding antifungal drug Amphotericin B strongly impairs the uptake of the fungal pathogen Candida albicans by human monocytes, suggesting a role of raft microdomains in the phagocytosis of the fungus. Time lapse confocal imaging indicated that Dectin-1, the C-type lectin receptor that recognizes Candida albicans cell wall-associated beta-glucan, is recruited to lipid rafts upon Candida albicans uptake by monocytes, supporting the notion that lipid rafts act as an entry platform. Interestingly disruption of lipid raft integrity and interference with fungus uptake do not alter cytokine production by monocytes in response to Candida albicans but drastically dampen fungus specific T cell response. In conclusion, these data suggest that monocyte lipid rafts play a crucial role in the innate and adaptive immune responses to Candida albicans in humans and highlight a new and unexpected immunomodulatory function of the antifungal drug Amphotericin B. PMID- 26562839 TI - The Influence of Chronic Ego Depletion on Goal Adherence: An Experience Sampling Study. AB - Although ego depletion effects have been widely observed in experiments in which participants perform consecutive self-control tasks, the process of ego depletion remains poorly understood. Using the strength model of self-control, we hypothesized that chronic ego depletion adversely affects goal adherence and that mental effort and motivation are involved in the process of ego depletion. In this study, 203 students reported their daily performance, mental effort, and motivation with respect to goal directed behavior across a 3-week time period. People with high levels of chronic ego depletion were less successful in goal adherence than those with less chronic ego depletion. Although daily effort devoted to goal adherence increased with chronic ego depletion, motivation to adhere to goals was not affected. Participants with high levels of chronic ego depletion showed a stronger positive association between mental effort and performance, but chronic ego depletion did not play a regulatory role in the effect of motivation on performance. Chronic ego depletion increased the likelihood of behavior regulation failure, suggesting that it is difficult for people in an ego-depletion state to adhere to goals. We integrate our results with the findings of previous studies and discuss possible theoretical implications. PMID- 26562840 TI - Processing Demands Impact 3-Year-Olds' Performance in a Spontaneous-Response Task: New Evidence for the Processing-Load Account of Early False-Belief Understanding. AB - Prior to age four, children succeed in non-elicited-response false-belief tasks but fail elicited-response false-belief tasks. To explain this discrepancy, the processing-load account argues that the capacity to represent beliefs emerges in infancy, as indicated by early success on non-elicited-response tasks, but that children's ability to demonstrate this capacity depends on the processing demands of the task and children's processing skills. When processing demands exceed young children's processing abilities, such as in standard elicited-response tasks, children fail despite their capacity to represent beliefs. Support for this account comes from recent evidence that reducing processing demands improves young children's performance: when demands are sufficiently reduced, 2.5-year olds succeed in elicited-response tasks. Here we sought complementary evidence for the processing-load account by examining whether increasing processing demands impeded children's performance in a non-elicited-response task. 3-year olds were tested in a preferential-looking task in which they heard a change-of location false-belief story accompanied by a picture book; across children, we manipulated the amount of linguistic ambiguity in the story. The final page of the book showed two images: one that was consistent with the main character's false belief and one that was consistent with reality. When the story was relatively unambiguous, children looked reliably longer at the false-belief consistent image, successfully demonstrating their false-belief understanding. When the story was ambiguous, however, this undermined children's performance: looking times to the belief-consistent image were correlated with verbal ability, and only children with verbal skills in the upper quartile of the sample demonstrated a significant preference for the belief-consistent image. These results support the processing-load account by demonstrating that regardless of whether a task involves an elicited response, children's performance depends on the processing demands of the task and their processing skills. These findings also have implications for alternative, deflationary accounts of early false belief understanding. PMID- 26562842 TI - Identification of microRNAs in Macaca fascicularis (Cynomolgus Monkey) by Homology Search and Experimental Validation by Small RNA-Seq and RT-qPCR Using Kidney Cortex Tissues. AB - MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M. fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M. fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys. PMID- 26562841 TI - Diversity of Mycobacterium tuberculosis across Evolutionary Scales. AB - Tuberculosis (TB) is a global public health emergency. Increasingly drug resistant strains of Mycobacterium tuberculosis (M.tb) continue to emerge and spread, highlighting adaptability of this pathogen. Most studies of M.tb evolution have relied on 'between-host' samples, in which each person with TB is represented by a single M.tb isolate. However, individuals with TB commonly harbor populations of M.tb numbering in the billions. Here, we use analyses of M.tb genomic data from within and between hosts to gain insight into influences shaping genetic diversity of this pathogen. We find that the amount of M.tb genetic diversity harbored by individuals with TB can vary dramatically, likely as a function of disease severity. Surprisingly, we did not find an appreciable impact of TB treatment on M.tb diversity. In examining genomic data from M.tb samples within and between hosts with TB, we find that genes involved in the regulation, synthesis, and transportation of immunomodulatory cell envelope lipids appear repeatedly in the extremes of various statistical measures of diversity. Many of these genes have been identified as possible targets of selection in other studies employing different methods and data sets. Taken together, these observations suggest that M.tb cell envelope lipids are targets of selection within hosts. Many of these lipids are specific to pathogenic mycobacteria and, in some cases, human-pathogenic mycobacteria. We speculate that rapid adaptation of cell envelope lipids is facilitated by functional redundancy, flexibility in their metabolism, and their roles mediating interactions with the host. PMID- 26562843 TI - Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats. AB - BACKGROUND: We have previously reported that high glucose impairs coronary vasodilation by reducing voltage-gated K+ (Kv) channel activity. However, the underlying mechanisms remain unknown. Advanced glycation end products (AGEs) are potent factors that contribute to the development of diabetic vasculopathy. The aim of this study was to investigate the role of AGEs in high glucose-induced impairment of Kv channels-mediated coronary vasodilation. METHODS: Patch-clamp recording and molecular biological techniques were used to assess the function and expression of Kv channels. Vasodilation of isolated rat small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and streptozotocin-induced diabetic rats with aminoguanidine, the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs. RESULTS: Incubation of VSMCs with high glucose reduced Kv current density by 60.4 +/- 4.8%, and decreased expression of Kv1.2 and Kv1.5 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high glucose-induced impairment of Kv channels. In addition, diabetic rats manifested reduced Kv channels-mediated coronary dilation (9.3 +/- 1.4% vs. 36.9 +/- 1.4%, P < 0.05), which was partly corrected by the treatment with aminoguanidine (24.4 +/ 2.2% vs. 9.3 +/- 1.4%, P < 0.05). CONCLUSIONS: Excessive formation of AGEs impairs Kv channels in VSMCs, then leading to attenuation of Kv channels-mediated coronary vasodilation. PMID- 26562845 TI - Dramatic increase in preexposure prophylaxis use among MSM in Washington state. AB - OBJECTIVE: HIV preexposure prophylaxis (PrEP) is efficacious, but uptake has been slow. In Washington State, most insurance plans, including Medicaid, pay for PrEP, and the state supports a PrEP drug assistance program. We assessed trends in PrEP awareness and use among MSM in Washington. DESIGN AND SETTING: Serial cross-sectional survey conducted annually at the Seattle Pride Parade between 2009 and 2015. METHODS: In a convenience sample of MSM who reside in Washington State and deny ever testing HIV positive (n = 2168), we evaluated the association between calendar year and self-report of PrEP uptake and awareness using descriptive statistics and multivariable relative risk and logistic regression. Regression models included HIV risk and demographic covariates. RESULTS: In 2015, 23% [95% confidence interval (CI): 16%, 31%] of high-risk MSM reported currently taking PrEP. The percentage of high-risk MSM who reported ever taking PrEP increased from 5% in 2012 to 31% in 2015. PrEP use among lower-risk MSM was low and stable, between 1 and 3% in 2012-2015. In multivariable analyses, PrEP use was associated with later calendar years (2015 vs. 2012: adjusted relative risk = 2.29, 95% CI: 1.16, 4.52) and elevated HIV risk (adjusted relative risk = 2.92, 95% CI: 2.00, 4.25). The percentage of high and lower-risk MSM who had heard of PrEP increased from 13 to 86% and from 29 to 58%, respectively. CONCLUSION: PrEP awareness is high and the use has rapidly increased over the last year among MSM in Seattle, Washington, USA. These findings demonstrate that high levels of PrEP use can be achieved among MSM at high-risk for HIV infection. PMID- 26562846 TI - The Effect of Loudness Variation on Velopharyngeal Function in Children with 22q11.2 Deletion Syndrome: A Pilot Study. AB - OBJECTIVE: Children with 22q11.2 deletion syndrome (22qDS) often require surgical intervention to treat velopharyngeal dysfunction (VPD). Although some studies have documented improved velopharyngeal (VP) closure under increased speaking effort, currently no studies have examined the effect of similar behavioral speech modifications on VP closure in children with 22qDS. The purpose of this pilot study was to explore the effect of loudness on VP closure during speech in children with 22qDS and persisting VPD. PATIENTS AND METHODS: Four children with 22qDS, posterior pharyngeal flap, and persisting mild VPD underwent pressure-flow testing while repeating words at habitual and increased loudness levels. Using a single-subject A-B design, descriptive statistics and graphical measures were used to examine differences in VP orifice area (VPA) and timing of closure in the habitual versus loud condition. RESULTS: Results were mixed. Median VPA decreased during some stimuli for 3 participants, but increased for 1 subject when speaking louder. Median duration of nasal airflow decreased for 3 participants in the loud condition. CONCLUSION: This study presents preliminary aerodynamic data regarding the plasticity of VP physiology in the 22qDS group. Further research is needed to determine how loudness impacts VP function in children with 22qDS. PMID- 26562847 TI - Numerical Context and Time Perception: Contrast Effects and the Perceived Duration of Numbers. AB - In the current study, we examined how the contextual repetition of magnitude information presented in either symbolic (Arabic digits) or nonsymbolic (numerosities) formats impacted on the perceived duration of a later occurring target number. The results of the current study demonstrated a time-magnitude bias in which, on average, large magnitude target numbers were judged to last for longer durations relative to small magnitude target numbers, regardless of notation (symbolic number and numerosity). Furthermore, context effects were found, in which a greater discrepancy in the target's magnitude from the initial context led to longer perceived duration ratings. However, this was found to be asymmetrical, occurring only for large magnitude targets. Additionally, the type of context effect was shown to be determined by whether the context was presented in the same notation as the target or a different notation. PMID- 26562848 TI - Finger Counting and (2D:4D) Digit Ratio in Spatial-Numerical Association. AB - It is reported that a canonical and cultural finger counting habit influences the spatial-numerical association. The digit ratio (the ratio between the lengths of the index and ring fingers as a putative indicator of prenatal androgen exposure) also plays an effect on space-number representation, reflecting a stronger left to-right number representation in people with a short index finger and longer ring finger (i.e., 2D:4D ratio). It is unknown whether the finger counting habit and digit ratio have an effect on spatial-numerical association independently from each other or whether they interact with each other. In Study 1, the digit ratio and finger counting mapping were recorded in right handers. The participants performed number-to-position, digit string bisection, and physical line bisection tasks. In the number-to-position task, a finger counting effect was found, as well as a significant interaction between factors. A digit ratio effect was observed in the digit string bisection task. In Study 2, digit ratio and finger counting mapping were recorded in right and left handers. The results showed that the finger counting habit influenced the spatial biases in both numerical tasks. A significant interaction between finger counting and digit ratio was found in both numerical tasks when only the left hand was considered. The results are discussed considering the embodied nature of the spatial numerical association. PMID- 26562844 TI - Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis. AB - OBJECTIVES: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. DESIGN: Collaborative analysis of data from eight European and three Canadian cohorts. METHODS: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4 cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression. RESULTS: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4 cell count below, or more than, 100 cells/MUl, respectively. There was no difference in mortality between subtypes A, B and C after viral failure. CONCLUSION: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors. PMID- 26562849 TI - Galileo's Dagger. AB - Galileo found that fine lines on a balance scale dazzled his eyes and were unreadable. So he used a grid of fine wires instead and ran his dagger across it, counting the number of auditory clicks. This is the first known experiment on sensory substitution. PMID- 26562850 TI - Perceptual Grouping Affects Haptic Enumeration Over the Fingers. AB - Spatial arrangement is known to influence enumeration times in vision. In haptic enumeration, it has been shown that dividing the total number of items over the two hands can speed up enumeration. Here we investigated how spatial arrangement of items and non-items presented to the individual fingers impacts enumeration times. More specifically, we tested whether grouping by proximity facilitates haptic serial enumeration (counting). Participants were asked to report the number of tangible items, amongst non-items, presented to the finger pads of both hands. In the first experiment, we divided the tangible items in one, two, or three groups that were defined by proximity (i.e., one nonitem in between two groups) and found that number of groups and not number of items were the critical factor in enumeration times. In a second experiment, we found that this grouping even takes place when groups extend across fingers of both hands. These results suggest that grouping by proximity affects haptic serial enumeration and that this grouping takes place on a spatial level possibly in addition to the somatotopic level. Our results support the idea that grouping by proximity, a principle introduced in vision, also greatly affects haptic processing of spatial information. PMID- 26562851 TI - Precision and Bias in Approximate Numerical Judgment in Auditory, Tactile, and Cross-modal Presentation. AB - Many studies have claimed that the numerosity of any set of discrete elements can be depicted by a genuinely abstract number representation, irrespective of whether they are presented in a visual, auditory, or tactile modality. However, in behavioral studies, some inconsistencies have been observed in the performance of number comparisons among different modalities. In this study, we have tested whether numerical comparisons of auditory, tactile, and cross-modal presentations would differ under adequate control of stimulus presentation, and, if so, how they would differ. The unimodal and cross-modal stimuli pairs were presented in sequential manner. We measured the Weber fractions (i.e., precision) and points of subjective equality (i.e., accuracy) of numerical discriminations in auditory, tactile, and crossmodal conditions. The results showed that the Weber fractions are constant over standard stimuli, indicating that the Weber's law holds for the range of numerical values that was tested. Furthermore, the Weber fractions are consistent over unimodal and cross-modal comparisons, and this indicates that there is no additional noise involved in the cross-modal comparisons. Interestingly, the bias measure showed that the number of auditory stimuli is systematically overestimated compared with that of tactile stimuli. PMID- 26562852 TI - Deaf Individuals Show a Leftward Bias in Numerical Bisection. AB - Consistent evidence suggests that deaf individuals conceive of numerical magnitude as a left-to-right-oriented mental number line, as typically observed in hearing individuals. When accessing this spatial representation of numbers, normally hearing individuals typically show an attentional bias to the left (pseudoneglect), resembling the attentional bias they show in physical space. Deaf individuals do not show pseudoneglect in representing external space, as assessed by a visual line bisection task. However, whether deaf individuals show attentional biases in representing numerical space has never been investigated before. Here we instructed groups of deaf and hearing individuals to quickly estimate (without calculating) the midpoint of a series of numerical intervals presented in ascending and descending order. Both hearing and deaf individuals were significantly biased toward lower numbers (i.e., the leftward side of the mental number line) in their estimations. Nonetheless, the underestimation bias was smaller in deaf individuals than in the hearing when bisecting pairs of numbers given in descending order. This result may depend on the use of different strategies by deaf and hearing participants or a less pronounced lateralization of deaf individuals in the control of spatial attention. PMID- 26562853 TI - Metaphoric Car Drawings By a 12-Year-Old Congenitally Blind Girl. AB - A 12-year-old congenitally-blind girl drew a car moving, stationary, and braking. For stationary, she put the wheels inside the car and, for braking, drew the wheels as rough rectangles. At the age verbal metaphor is understood (Winner, 1988), the girl invented metaphoric drawings. In these, what is shown is not what is meant. In late childhood, metaphor may be understood similarly in pictures and words and by the sighted and blind. PMID- 26562854 TI - Numerical Priming Between Touch and Vision Depends on Tactile Discrimination. AB - Although the interaction between vision and touch is of crucial importance for perceptual and bodily self-consciousness, only little is known regarding the link between conscious access and tactile processing. Here, we tested whether the numerical encoding of tactile stimuli depends on conscious discrimination. On each trial, participants received between zero and three taps at low, medium, or high intensity and had to enumerate the number of visual items subsequently presented as a visual target. We measured tactovisual numerical priming, that is, the modulation of reaction times according to the numerical distance between the visual target and tactile prime values. While numerical priming and repetition priming were respectively elicited by high and medium intensity stimuli, no effect was found for low intensity stimuli that were not discriminable. This suggests that numerical priming between touch and vision depends on tactile discrimination. We discuss our results considering recent advances in unconscious visual numerical priming. PMID- 26562855 TI - Robust Underestimation of Speed During Driving: A Field Study. AB - Traffic reports consistently identify speeding as a substantial source of accidents. Adequate driving speeds require reliable speed estimation; however, there is still a lack of understanding how speed perception is biased during driving. Therefore, we ran three experiments measuring speed estimation under controlled driving and lighting conditions. In the first experiment, participants had to produce target speeds as drivers or had to judge driven speed as passengers. Measurements were performed at daylight and at night. In the second experiment, participants were required to produce target speeds at dusk, under rapidly changing lighting conditions. In the third experiment, we let two cars approach and pass each other. Drivers were instructed to produce target speeds as well as to judge the speed of the oncoming vehicle. Here measurements were performed at daylight and at night, with full or dipped headlights. We found that passengers underestimated driven speed by about 20% and drivers went over the instructed speed by roughly the same amount. Interestingly, the underestimation of speed extended to oncoming cars. All of these effects were independent of lighting conditions. The consistent underestimation of speed could lead to potentially fatal situations where drivers go faster than intended and judge oncoming traffic to approach slower than it actually is. PMID- 26562856 TI - Illusions within an Illusion. AB - Effect of perceptual inversion on illusion figures seen monocularly was explored using Ponzo and Muller-Lyer stimuli. It was found that inversion nullified the Ponzo effect but not the Muller-Lyer effect. This suggests that the determinants of the two illusory effects differ in their origin. PMID- 26562857 TI - Interaction of Number Magnitude and Auditory Localization. AB - The interplay of perception and memory is very evident when we perceive and then recognize familiar stimuli. Conversely, information in long-term memory may also influence how a stimulus is perceived. Prior work on number cognition in the visual modality has shown that in Western number systems long-term memory for the magnitude of smaller numbers can influence performance involving the left side of space, while larger numbers have an influence toward the right. Here, we investigated in the auditory modality whether a related effect may bias the perception of sound location. Subjects (n = 28) used a swivel pointer to localize noise bursts presented from various azimuth positions. The noise bursts were preceded by a spoken number (1-9) or, as a nonsemantic control condition, numbers that were played in reverse. The relative constant error in noise localization (forward minus reversed speech) indicated a systematic shift in localization toward more central locations when the number was smaller and toward more peripheral positions when the preceding number magnitude was larger. These findings do not support the traditional left-right number mapping. Instead, the results may reflect an overlap between codes for number magnitude and codes for sound location as implemented by two channel models of sound localization, or possibly a categorical mapping stage of small versus large magnitudes. PMID- 26562859 TI - Limitations of the Oriented Difference of Gaussian Filter in Special Cases of Brightness Perception Illusions. AB - The Oriented Difference of Gaussian (ODOG) filter of Blakeslee and McCourt has been successfully employed to explain several brightness perception illusions which include illusions of both brightness-contrast type, for example, Simultaneous Brightness Contrast and Grating Induction and the brightness assimilation type, for example, the White effect and the shifted White effect. Here, we demonstrate some limitations of the ODOG filter in predicting perceived brightness by comparing the ODOG responses to various stimuli (generated by varying two parameters, namely, test patch length and spatial frequency) with experimental observations of the same. PMID- 26562858 TI - Number As a Primary Perceptual Attribute: A Review. AB - Although humans are the only species to possess language-driven abstract mathematical capacities, we share with many other animals a nonverbal capacity for estimating quantities or numerosity. For some time, researchers have clearly differentiated between small numbers of items--less than about four--referred to as the subitizing range, and larger numbers, where counting or estimation is required. In this review, we examine more recent evidence suggesting a further division, between sets of items greater than the subitizing range, but sparse enough to be individuated as single items; and densely packed stimuli, where they crowd each other into what is better considered as a texture. These two different regimes are psychophysically discriminable in that they follow distinct psychophysical laws and show different dependencies on eccentricity and on luminance levels. But provided the elements are not too crowded (less than about two items per square degree in central vision, less in the periphery), there is little evidence that estimation of numerosity depends on mechanisms responsive to texture. The distinction is important, as the ability to discriminate numerosity, but not texture, correlates with formal maths skills. PMID- 26562860 TI - Attending at a Low Intensity Increases Impulsivity in an Auditory Sustained Attention to Response Task. AB - Why attention lapses during prolonged tasks is debated, specifically whether errors are a consequence of under-arousal or exerted effort. To explore this, we investigated whether increased impulsivity is associated with effortful processing by modifying the demand of a task by presenting it at a quiet intensity. Here, we consider whether attending at low but detectable levels affects impulsivity in a population with intact hearing. A modification of the Sustained Attention to Response Task was used with auditory stimuli at two levels: the participants' personal "lowest detectable" level and a "normal speaking" level. At the quiet intensity, we found that more impulsive responses were made compared with listening at a normal speaking level. These errors were not due to a failure in discrimination. The findings suggest an increase in processing time for auditory stimuli at low levels that exceeds the time needed to interrupt a planned habitual motor response. This leads to a more impulsive and erroneous response style. These findings have important implications for understanding the nature of impulsivity in relation to effortful processing. They may explain why a high proportion of individuals with hearing loss are also diagnosed with Attention Deficit Hyperactivity Disorder. PMID- 26562861 TI - What Is the Role of Manual Preference in Hand-Digit Mapping During Finger Counting? A Study in a Large Sample of Right- and Left-Handers. AB - The goal of the present study was to test whether there is a relationship between manual preference and hand-digit mapping in 369 French adults with similar numbers of right- and left-handers. Manual laterality was evaluated with the finger tapping test to evaluate hand motor asymmetry, and the Edinburgh handedness inventory was used to assess manual preference strength (MPS) and direction. Participants were asked to spontaneously "count on their fingers from 1 to 10" without indications concerning the hand(s) to be used. The results indicated that both MPS and hand motor asymmetry affect the hand-starting preference for counting. Left-handers with a strong left-hand preference (sLH) or left-hand motor asymmetry largely started to count with their left hand (left starter), while right-handers with a strong right-hand preference (sRH) or right hand motor asymmetry largely started to count with their right hand (right starter). Notably, individuals with weak MPS did not show a hand-starting preference. These findings demonstrated that manual laterality contributes to finger counting directionality. Lastly, the results showed a higher proportion of sLH left-starter individuals compared with sRH right-starters, indicating an asymmetric bias of MPS on hand-starting preference. We hypothesize that the higher proportion of sLH left-starters could be explained by the congruence between left-to-right hand-digit mapping and left-to-right mental number line representation that has been largely reported in the literature. Taken together, these results indicate that finger-counting habits integrate biological and cultural information. PMID- 26562862 TI - Analog Magnitudes Support Large Number Ordinal Judgments in Infancy. AB - Few studies have explored the source of infants' ordinal knowledge, and those that have are equivocal regarding the underlying representational system. The present study sought clear evidence that the approximate number system, which underlies children's cardinal knowledge, may also support ordinal knowledge in infancy; 10 - to 12-month-old infants' were tested with large sets (>3) in an ordinal choice task in which they were asked to choose between two hidden sets of food items. The difficulty of the comparison varied as a function of the ratio between the sets. Infants reliably chose the greater quantity when the sets differed by a 2:3 ratio (4v6 and 6v9), but not when they differed by a 3:4 ratio (6v8) or a 7:8 ratio (7v8). This discrimination function is consistent with previous studies testing the precision of number and time representations in infants of roughly this same age, thus providing evidence that the approximate number system can support ordinal judgments in infancy. The findings are discussed in light of recent proposals that different mechanisms underlie infants' reasoning about small and large numbers. PMID- 26562863 TI - Grouping Factors and the Reverse Contrast Illusion. AB - In simultaneous lightness contrast, two identical gray target squares lying on backgrounds of different intensities appear different in lightness. Traditionally, this illusion was explained by lateral inhibitory mechanisms operating retinotopically. More recently, spatial filtering models have been preferred. We report tests of an anchoring theory account in which the illusion is attributed to grouping rules used by the visual system to compute lightness. We parametrically varied the belongingness of two gray target bars to their respective backgrounds so that they either appeared to group with a set of bars flanking them, or they appeared to group with their respective backgrounds. In all variations, the retinal adjacency of the gray squares and their backgrounds was essentially unchanged. We report data from seven experiments showing that manipulation of the grouping rules governs the size and direction of the simultaneous lightness contrast illusion. These results support the idea that simultaneous lightness contrast is the product of anchoring within perceptual groups. PMID- 26562864 TI - Temporal Visual Mechanisms May Mediate Compensation for Macular Pigment. AB - Macular pigment (MP) is a pre-receptoral filter that is diet derived and deposited in relatively high optical density in the foveal region of the retina. Due to its yellow coloration, MP absorbs light of relatively short wavelengths, ranging from 400 nm to 520 nm. Despite the spectral and spatial nonuniformity imposed upon the sensory retina by MP, perception appears to be relatively uniform across the central visual field. MP therefore offers an opportunity to determine experimentally potential mechanisms responsible for mediating this uniformity. After assessing, in 14 subjects, MP's effects on the temporal sensitivity of both the short-wavelength- and middle-/long-wavelength-sensitive visual pathways, it appears that the visual system compensates for absorption of short-wavelength light by MP by slowing the sampling rate of short-wavelength cones and by increasing the processing speed of middle-/long-wavelength-sensitive cones. This mechanism could work via temporal summation or a temporal neural code, whereby slower response dynamics lead to amplification of relatively weak signals. PMID- 26562865 TI - Priming of Visual Search Facilitates Attention Shifts: Evidence From Object Substitution Masking. AB - Priming of visual search strongly affects visual function, releasing items from crowding and during free-choice primed targets are chosen over unprimed ones. Two accounts of priming have been proposed: attentional facilitation of primed features and postperceptual episodic memory retrieval that involves mapping responses to visual events. Here, well-known masking effects were used to assess the two accounts. Object-substitution masking has been considered to reflect attentional processing: It does not occur when a target is precued and is strengthened when distractors are present. Conversely, metacontrast masking has been connected to lower level processing where attention exerts little effect. If priming facilitates attention shifts, it should mitigate object-substitution masking, while lower level masking might not be similarly influenced. Observers searched for an odd-colored target among distractors. Unpredictably (on 20% of trials), object-substitution masks or metacontrast masks appeared around the target. Object-substitution masking was strongly mitigated for primed target colors, while metacontrast masking was mostly unaffected. This argues against episodic retrieval accounts of priming, placing the priming locus firmly within the realm of attentional processing. The results suggest that priming of visual search facilitates attention shifts to the target, which allows better spatiotemporal resolution that overcomes object-substitution masking. PMID- 26562866 TI - Tactile Toe Agnosia and Percept of a "Missing Toe" in Healthy Humans. AB - A disturbance of body representation is central to many neurological and psychiatric conditions, but the mechanisms by which body representations are constructed by the brain are not fully understood. We demonstrate a directional disturbance in tactile identification of the toes in healthy humans. Nineteen young adult participants underwent tactile stimulation of the digits with the eyes closed and verbally reported the identity of the stimulated digit. In the majority of individuals, responses to the second and third toes were significantly biased toward the laterally neighboring digit. The directional bias was greater for the nondominant foot and was affected by the identity of the immediately preceding stimulated toe. Unexpectedly, 9/19 participants reported the subjective experience of a "missing toe" or "missing space" during the protocol. These findings challenge current models of somatosensory localization, as they cannot be explained simply by a lack of distinct representations for toes compared with fingers, or by overt toe-finger correspondences. We present a novel theory of equal spatial representations of digit width combined with a "preceding neighbor" effect to explain the observed phenomena. The diagnostic implications for neurological disorders that involve "digit agnosia" are discussed. PMID- 26562867 TI - Effects of Contextual Information on Seeing Pareidolic Religious Inscriptions on an Artifact: Implications for the Shroud of Turin. AB - Several reports suggest that images of the Shroud of Turin contain faint religious inscriptions that support the view that the Shroud has special religious significance. Against this background, we investigated effects of contextual information on detecting religious inscriptions using an image of plain modern linen with no religious provenance and containing no writing. The image was viewed in three contexts: In the Neutral Context, participants were told that the image was of a simple piece of linen; in the Religious Context, participants were told that the image was of an important religious artifact; and in the Religious Context + Options condition, participants were also given plausible word options. Very few words were detected in the Neutral Context, significantly more in the Religious Context, and most in the Religious Context+Options condition. Some implications of these findings for reports of inscriptions in the context-laden conditions surrounding the Shroud of Turin are discussed. PMID- 26562868 TI - Allocentric Spatial Performance Higher in Early-Blind and Sighted Adults Than in Retinopathy-of-Prematurity Adults. AB - The question as to whether people totally blind since infancy process allocentric or external spatial information like the sighted has caused considerable debate within the literature. Due to the extreme rarity of the population, researchers have often included individuals with retinopathy of prematurity (RoP--over oxygenation at birth) within the sample. However, RoP is inextricably confounded with prematurity per se. Prematurity, without visual disability, has been associated with spatial processing difficulties. In this experiment, blindfolded sighted participants and two groups of functionally totally blind participants heard text descriptions from a survey (allocentric) or route (egocentric) perspective. One blind group lost their sight due to RoP and a second group before 24 months of age. The accuracy of participants' mental representations derived from the text descriptions was assessed via questions and maps. The RoP participants had lower scores than the sighted and early blind, who performed similarly. In other words, it was not visual impairment alone that resulted in impaired allocentric spatial performance in this task but visual impairment together with RoP. This finding may help explain the contradictions within the existing literature on the role of vision in allocentric spatial processing. PMID- 26562870 TI - Two Left Hands, Ten Interlaced Fingers: A New Rubber Hand Illusion. AB - A variation on the rubber hand paradigm elicits an illusion in which the participant's sense of body ownership can switch back and forth between two viewed prosthetic hands. The interlaced fingers paradigm involves three prosthetic left hands: Two are positioned in full view of the participant, with their fingers interlaced, and the fingers of a third prosthetic hand are interlaced with the fingers of the participant's left hand, which is hidden from view. The examiner alternates brushstrokes to the two viewed prosthetic hands, while administering synchronous brushstrokes to the participant's hidden hand. Most participants experience ownership for the prosthetic hand that is being stroked at a given moment. PMID- 26562869 TI - Recognizing Dynamic Faces in Malaysian Chinese Participants. AB - High performance level in face recognition studies does not seem to be replicable in real-life situations possibly because of the artificial nature of laboratory studies. Recognizing faces in natural social situations may be a more challenging task, as it involves constant examination of dynamic facial motions that may alter facial structure vital to the recognition of unfamiliar faces. Because of the incongruences of recognition performance, the current study developed stimuli that closely represent natural social situations to yield results that more accurately reflect observers' performance in real-life settings. Naturalistic stimuli of African, East Asian, and Western Caucasian actors introducing themselves were presented to investigate Malaysian Chinese participants' recognition sensitivity and looking strategies when performing a face recognition task. When perceiving dynamic facial stimuli, participants fixated most on the nose, followed by the mouth then the eyes. Focusing on the nose may have enabled participants to gain a more holistic view of actors' facial and head movements, which proved to be beneficial in recognizing identities. Participants recognized all three races of faces equally well. The current results, which differed from a previous static face recognition study, may be a more accurate reflection of observers' recognition abilities and looking strategies. PMID- 26562875 TI - Mouse Ability to Perceive Subjective Contours. AB - In contrast to the previously held notion that mice have a weak visual system, it is now generally accepted that mice can perceive rather complicated figures in various contexts such as in cognitive experiments and in social settings. Here, we show that mice could even be capable of perceiving a visual illusion- subjective contours. This illusion requires the visual system to compensate for a lack of visual information in compressed 2D images on the retina. In this experiment, we trained mice to respond appropriately to a rectangle-shaped rewarded figure of specific orientation in a two-choice visual discrimination task with a touchscreen monitor. In Transfer Test 1, mice could discriminate illusory rectangle-shaped figures significantly as compared with a figure, which did not induce illusory figures. In Transfer Test 2, the choice rate of targets decreased with imperfect illusory figures, which produced weak perception of rotated or deficient inducers. Moreover, in Transfer Test 3, mice could not discriminate the low-resolution illusory figure, which also induced weak perception. These results demonstrated the possibility that mice might be useful for investigating fundamental properties of the neural visual system. PMID- 26562876 TI - Children's Approximate Number System in Haptic Modality. AB - The approximate number system (ANS) is a primitive system used to estimate quantities. It can process quantities in visual and auditory modalities. The aim of the present study was to examine whether ANS can process quantities presented haptically. Moreover, to assess age-related changes, two groups of children (5- and 7-year-olds) were compared. In a newly designed haptic task, children compared two arrays of dots by touching them simultaneously using both hands, without seeing them, and for limited duration to prevent counting. Using Panamath, a frequently used visual ANS task, we verified that our population exhibited the typical pattern of approximation with visual arrays: Older children outperformed younger children, and an increased ratio between the two quantities to be compared led to more accurate responses. Performance in the haptic task revealed that children, in both age-groups, were able to haptically compare two quantities above chance level, with improved performance in older compared with younger children. Moreover, our results revealed a ratio effect, a well-known signature of the ANS. These findings suggest that haptic numerical discrimination in children is dictated by the ANS, and that ANS acuity measured with a haptic task improves with age, as commonly observed with the visual task. PMID- 26562877 TI - SNARC Effect in Different Effectors. AB - The SNARC (spatial numerical association of response codes) effect, indicating that subjects react faster to the left for small numbers and to the right for large numbers, is used as evidence for the idea that humans use space to organize number representations. Previous studies compared the SNARC effect across sensory modalities within participants and concluded modality independence. So far, it is unknown what sensory-to-motor mappings are involved in generating the SNARC effect and whether these mappings are identical for different effectors within subjects. Hence, we tested whether the SNARC effect is effector specific. Participants performed an auditory parity judgment task and responded with three different effectors: finger (button release), eyes (saccades), and arm (pointing). The SNARC effect occurred in each effector but varied in strength across the effectors. Across subjects, we found a significant correlation of SNARC strength for finger and arm responses suggesting the use of a shared sensory-to-motor mapping. SNARC strength did not correlate, however, between finger and eyes or arm and eyes. An additional statistical analysis based on conditional probabilities provided further evidence for SNARC-effector specificity. Taken together, our results suggest that the sensory-to-motor mapping is not as tight as it would be expected if the SNARC effect was effector independent. PMID- 26562878 TI - Spatial Frequency Components of Images Modulate Neuronal Activity in Monkey Amygdala. AB - Processing the spatial frequency components of an image is a crucial feature for visual perception, especially in recognition of faces. Here, we study the correlation between spatial frequency components of images of faces and neuronal activity in monkey amygdala while performing a visual recognition task. The frequency components of the images were analyzed using a fast Fourier transform for 40 spatial frequency ranges. We recorded 65 neurons showing statistically significant responses to at least one of the images used as a stimulus. A total of 37 of these neurons (n = 37) showed significant responses to at least three images, and in eight of them (8/37, 22%), we found a statistically significant correlation between neuron response and the modulus amplitude of at least one frequency range present in the images. Our results indicate that high spatial frequency and low spatial frequency components of images influence the activity of amygdala neurons. PMID- 26562879 TI - The Influence of Attention Set, Working Memory Capacity, and Expectations on Inattentional Blindness. AB - The probability of inattentional blindness, the failure to notice an unexpected object when attention is engaged on some primary task, is influenced by contextual factors like task demands, features of the unexpected object, and the observer's attention set. However, predicting who will notice an unexpected object and who will remain inattentionally blind has proven difficult, and the evidence that individual differences in cognition affect noticing remains ambiguous. We hypothesized that greater working memory capacity might modulate the effect of attention sets on noticing because working memory is associated with the ability to focus attention selectively. People with greater working memory capacity might be better able to attend selectively to target items, thereby increasing the chances of noticing unexpected objects that were similar to the attended items while decreasing the odds of noticing unexpected objects that differed from the attended items. Our study (N = 120 participants) replicated evidence that task-induced attention sets modulate noticing but found no link between noticing and working memory capacity. Our results are largely consistent with the idea that individual differences in working memory capacity do not predict noticing of unexpected objects in an inattentional blindness task. PMID- 26562880 TI - Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. AB - The objective of this study was to determine vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 20 ME/CFS patients and 20 matched (age, gender) controls were recruited to the study. Pattern-related visual stress was determined using the Pattern Glare Test. Participants viewed three patterns, the spatial frequencies (SF) of which were 0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg). They reported the number of distortions they experienced when viewing each pattern. ME/CFS patients exhibited significantly higher pattern glare scores than controls for the mid-SF pattern. Mid-high SF differences were also significantly higher in patients than controls. These findings provide evidence of altered visual perception in ME/CFS. Pattern-related visual stress may represent an identifiable clinical feature of ME/CFS that will prove useful in its diagnosis. However, further research is required to establish if these symptoms reflect ME/CFS-related changes in the functioning of sensory neural pathways. PMID- 26562882 TI - Effects of Numerosity Range on Tactile and Visual Enumeration. AB - Our study explores tactile enumeration using both hands and investigates the effects of numerosity range's (NR) on general enumeration. In Experiment 1, using custom-made vibro-tactile apparatus, we replicated results of Cohen, Naparstek, and Henik (2014, Acta Psychologica, 150C, 26-34) and again found a moderate increase in RT up to four stimuli and then a decrease for five stimuli. In Experiment 2, we used a within participants design and compared NR 1 to 5 and 1 to 10 in tactile and visual enumeration. The results showed that enumeration for NR 5 to 1 was faster than for NR 1 to 10, especially for numerosities four and five. Within NR 1 to 10, in the visual modality the subitizing range was 4, the counting range was from 5 to 9, and there was an end effect of 10 dots. In the tactile modality, when excluding one-hand arrangements, the subitizing range was 2, the counting range was from 3 to 5, there was an acceleration of counting from 5 and on, and there was an end effect for 10 stimuli that was stronger than for 10 visual stimuli. We suggest that NR influences enumeration and that number-hand association (i.e. resulting from finger counting) influences enumeration, resulting in faster counting. PMID- 26562881 TI - Haptic Object Recognition is View-Independent in Early Blind but not Sighted People. AB - Object recognition, whether visual or haptic, is impaired in sighted people when objects are rotated between learning and test, relative to an unrotated condition, that is, recognition is view-dependent. Loss of vision early in life results in greater reliance on haptic perception for object identification compared with the sighted. Therefore, we hypothesized that early blind people may be more adept at recognizing objects despite spatial transformations. To test this hypothesis, we compared early blind and sighted control participants on a haptic object recognition task. Participants studied pairs of unfamiliar three dimensional objects and performed a two-alternative forced-choice identification task, with the learned objects presented both unrotated and rotated 180 degrees about they-axis. Rotation impaired the recognition accuracy of sighted, but not blind, participants. We propose that, consistent with our hypothesis, haptic view independence in the early blind reflects their greater experience with haptic object perception. PMID- 26562886 TI - First, believe your eyes. PMID- 26562887 TI - Chromatic Dimensions Earthy, Watery, Airy, and Fiery. AB - In our study, for a small number of antonyms, we investigate whether they are cross-modally or ideaesthetically related to the space of colors. We analyze the affinities of seven antonyms (cold-hot, dull-radiant, dead-vivid, soft-hard, transparent-chalky, dry-wet, and acid-treacly) and their intermediate connotations (cool-warm, matt-shiny, numb-lively, mellow-firm, semi-transparent opaque, semi-dry-moist, and sour-sweet) as a function of color. We find that some antonyms relate to chromatic dimensions, others to achromatic ones. The cold-hot antonym proves to be the most salient dimension. The dry-wet dimension coincides with the cold-hot dimension, with dry corresponding to hot and wet to cold. The acid-treacly dimension proves to be transversal to the cold-hot dimension; hence, the pairs mutually span the chromatic domain. The cold-hot and acid-treacly antonyms perhaps recall Hering's opponent color system. The dull-radiant, transparent-chalky, and dead-vivid pairs depend little upon chromaticity. Of all seven antonyms, only the soft-hard one turns out to be independent of the chromatic structure. PMID- 26562888 TI - Migraine in Synesthetes and Nonsynesthetes: A Prevalence Study. AB - Synesthesia is a neurological condition in which an inducer stimulus in one sense leads to a concurrent percept in a second sense. The immune hypothesis of synesthesia links synesthesia to immune-related conditions such as migraine. More specifically, migraine with aura may be linked to grapheme-color synesthesia as both involve cortical hyperexcitability. In this study, 161 female synesthetes, and 92 female nonsynesthetes, completed an online questionnaire about synesthesia and migraine. We found no general link between migraine and synesthesia nor between migraine with aura and grapheme-color synesthesia. Exploratory analyses, however, showed that certain types of synesthetic inducer (non-linguistic visual experiences, scent, taste, emotion and personality) were associated with visual disturbances in headache among female participants, and touch as a concurrent was associated with migraine with aura. On the basis of our exploratory analyses, we hypothesize that specific subtypes of synesthesia are related to migraine. The relationship between these two conditions is likely to become clearer as research on the underlying causes of synesthesia and migraine progresses. PMID- 26562889 TI - Targets Need Their Own Personal Space: Effects of Clutter on Multiple-Target Search Accuracy. AB - Visual search is an essential task for many lifesaving professions; airport security personnel search baggage X-ray images for dangerous items and radiologists examine radiographs for tumors. Accuracy is critical for such searches; however, there are potentially negative influences that can affect performance; for example, the displays can be cluttered and can contain multiple targets. Previous research has demonstrated that clutter can hurt search performance and a second target is less likely to be detected in a multiple target search after a first target has been found, which raises a concern-how does clutter affect multiple-target search performance? The current study explored clutter in a multiple-target search paradigm, where there could be one or two targets present, and targets appeared in varying levels of clutter. There was a significant interaction between clutter and target number: Increasing levels of clutter did not affect single-target detection but did reduce detection of a second target. Multiple-target search accuracy is known to be sensitive to contextual influences, and the current results reveal a specific effect wherein clutter disproportionally affected multiple-target search accuracy. These results suggest that the detection and processing of a first target might enhance the masking effects of clutter around a second target. PMID- 26562890 TI - The Unilateral Mean Luminance Alters Additive Internal Noise in Normal Vision. AB - Luminance has been found to play a modulating role in the processes of many visual tasks. However, the mechanisms underlying the modulation role of luminance have been little studied, and the conclusions have been controversial. Here, using a dichoptic viewing paradigm by varying the luminance in one eye while measuring the contrast-detection threshold in the other eye, we studied the effect of different unilateral mean luminance values on the detectability of sine wave gratings against backgrounds of various levels of white noise in normal subjects. We found that unilateral luminance altered the additive internal noise within a perceptual template model framework, with low luminance increasing the additive internal noise and high luminance reducing it. This finding helps to reveal how luminance modulates contrast detection and its relative mechanisms. PMID- 26562891 TI - The Mirrored Hand Illusion: I Control, So I Possess? AB - Certain situations may not only cause people to misjudge external information but also distort people's perception of themselves. The present study is the first to report the mirrored hand illusion which could be generated when the experimenter imitated the fist-clenching movements of the subject synchronously. The subjects formed the illusion that the experimenter's hand was "something I can control" when being imitated synchronously. In addition, a sense of ownership over the alien hand was established by integrating multisensory signals and comparing these signals with preexisting body presentations. This method might represent a new avenue for research on the formation of self-consciousness. PMID- 26562894 TI - Bilateral Symmetry of Distortions of Tactile Size Perception. AB - The perceived distance between touches on the limbs is generally bigger for distances oriented across the width of the limb than for distances oriented along the length of the limb. The present study aimed to investigate the coherence of such distortions of tactile size perception across different skin surfaces. We investigated distortions of tactile size perception on the dorsal and palmar surfaces of both the left and right hands as well as the forehead. Participants judged which of two tactile distances felt larger. One distance was aligned with the proximodistal axis (along the body), the other with the mediolateral axis (across the body). Clear distortions were found on all five skin surfaces, with stimuli oriented across the width of the body being perceived as farther apart than those oriented along the length of the body. Consistent with previous results, distortions were smaller on the palmar than on the dorsal hand surface. Distortion on the forehead was intermediate between the dorsal and palmar surfaces. There were clear correlations between distortion on the left and right hands, for both the dorsal and palmar skin surfaces. In contrast, within each hand, there was no significant correlation between the two skin surfaces. Distortion on the forehead was not significantly correlated with that on any of the other skin surfaces. These results provide evidence for bilaterally symmetric representations underlying tactile size perception. PMID- 26562895 TI - Afterimages are biased by top-down information. AB - The afterimage illusion refers to a complementary colored image continuing to appear in the observer's vision after the exposure to the original image has ceased. It is assumed to be a phenomenon of the primary visual pathway, caused by overstimulation of photoreceptors of the retina. The aim of the present study was to investigate the nature of afterimage perceptions; mainly whether it is a mere physical, that is, low-level effect or whether it can be modulated by top-down processes, that is, high-level processes. Participants were first exposed to five either strongly female or male faces (Experiment 1), objects highly associated with female or male gender (Experiment 2) or female versus male names (Experiment 3), followed by a negativated image of a gender-neutral face which had to be fixated for 20s to elicit an afterimage. Participants had to rate their afterimages according to sexual dimorphism, showing that the afterimage of the gender-neutral face was perceived as significantly more female in the female priming condition compared with the male priming condition, independently of the priming quality (faces, objects, and names). Our results documented, in addition to previously presumed bottom-up mechanisms, a prominent influence of top-down processing on the perception of afterimages via priming mechanisms (female primes led to more female afterimage perception). PMID- 26562896 TI - Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level. AB - In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. PMID- 26562897 TI - Influence of Perceived Height, Masculinity, and Age on Each Other and on Perceptions of Dominance in Male Faces. AB - Several studies have examined the individual effects of facial cues to height, masculinity, and age on interpersonal interactions and partner preferences. We know much less about the influence of these traits on each other. We, therefore, examined how facial cues to height, masculinity, and age influence perceptions of each other and found significant overlap. This suggests that studies investigating the effects of one of these traits in isolation may need to account for the influence of the other two traits. Additionally, there is inconsistent evidence on how each of these three facial traits affects dominance. We, therefore, investigated how varying such traits influences perceptions of dominance in male faces. We found that increases in perceived height, masculinity, and age (up to 35 years) all increased facial dominance. Our results may reflect perceptual generalizations from sex differences as men are on average taller, more dominant, and age faster than women. Furthermore, we found that the influences of height and age on perceptions of dominance are mediated by masculinity. These results give us a better understanding of the facial characteristics that convey the appearance of dominance, a trait that is linked to a wealth of real-world outcomes. PMID- 26562898 TI - What Gaze Fixation and Pupil Dilation Can Tell Us About Perceived Differences Between Abstract Art by Artists Versus by Children and Animals. AB - People with no arts background often misunderstand abstract art as requiring no skill. However, adults with no art background discriminate paintings by abstract expressionists from superficially similar works by children and animals. We tested whether participants show different visual exploration when looking at paintings by artists' versus children or animals. Participants sat at an eye tracker and viewed paintings by artists paired with "similar" paintings by children or animals, and were asked which they preferred and which was better. Mean duration of eye gaze fixations, total fixation time, and spatial extent of visual exploration was greater to the artist than child or animal images in response to quality but not preference. Pupil dilation was greater to the artist images in response to both questions and greater in response to the quality than preference question. Explicit selections of images paralleled total fixation times: Participants selected at chance for preference, but selected the artist images above chance in response to quality. Results show that lay adults respond differently on both an implicit as well as explicit measure when thinking about preference versus quality in art and discriminate abstract paintings by artists from superficially similar works by children and animals, despite the popular misconception by the average viewer that "my kid could have done that." PMID- 26562902 TI - 38th European Conference on Visual Perception (ECVP) 2015 Liverpool. PMID- 26562899 TI - Variation in Photos of the Same Face Drives Improvements in Identity Verification. AB - People are poor at matching the identity of unfamiliar faces, but very good at identifying familiar faces. Theoretical accounts suggest that representations derived from exposure to variation are instrumental in driving this familiarity based improvement. In support of this, recent work shows that providing multiple photographs of an unfamiliar face improves identity verification accuracy. Here, we test whether the extent of variation is critical to this improvement, by manipulating the degree of within-identity variation that participants are exposed to in a sequential matching test. Participants were more accurate and adopted more liberal response criteria, when matching high-variability pairs to probe images, compared with either low-variability pairs or single images. Importantly, benefits of variation are not explained by independent contributions of single images, suggesting that people extrapolate information across images to produce gains in identification accuracy. These results suggest that photo-ID can be improved by incorporating broader ranges of variation in facial appearance. PMID- 26562903 TI - The Vision of Alfred Yarbus. PMID- 26562904 TI - About My Father Alfred Lukyanovich Yarbus. PMID- 26562905 TI - Scientific Activity of Alfred Yarbus: The Stages of Research Work, Senior and Younger Colleagues, Conditions of Investigations. PMID- 26562906 TI - How Were Eye Movements Recorded Before Yarbus? AB - Alfred Yarbus introduced a new dimension of precision in recording how the eyes moved, either when attempts were made to keep them stationary or when scanning pictures. Movements of the eyes had been remarked upon for millennia, but recording how they move is a more recent preoccupation. Emphasis was initially placed on abnormalities of oculomotor function (like strabismus) before normal features were considered. The interest was in where the eyes moved to rather than determining how they got there. The most venerable technique for examining ocular stability involved comparing the relative motion between an afterimage and a real image. In the late 18th century, Wells compared afterimages generated before body rotation with real images observed following it when dizzy; he described both lateral and torsional nystagmus, thereby demonstrating the directional discontinuities in eye velocities. At around the same time Erasmus Darwin used afterimages as a means of demonstrating ocular instability when attempting to fixate steadily. However, the overriding concern in the 19th century was with eye position rather than eye movements. Thus, the characteristics of nystagmus were recorded before those of saccades and fixations. Eye movements during reading were described by Hering and by Lamare (working in Javal's laboratory) in 1879; both used similar techniques of listening (with tubes placed over the eyelids) to the sounds made during contractions of the extraocular muscles. Photographic records of eye movements during reading were made by Dodge early in the 20th century, and this stimulated research using a wider array of patterns. Eye movements over pictures were examined by Stratton and later by Buswell, who drew attention to the effects of instructions on the pattern of eye movements. In midcentury, attention shifted back to the stability of the eyes during fixation, with the emphasis on involuntary movements. The suction cap methods developed by Yarbus were applied with some success to recording the perceptual effects of retinal image stabilization. It is an historical irony that the accuracy of image stabilization with contact lenses was assessed by comparison with the oldest method for examining eye movements--afterimages. PMID- 26562907 TI - From Exploration to Fixation: An Integrative View of Yarbus's Vision. AB - Alfred Lukyanovich Yarbus (1914-1986) pioneered the study of stabilized retinal images, miniature eye movements, and the cognitive influences that act on visual scanning. Yarbus's studies of these different topics have remained fundamentally disconnected and independent of each other, however. In this review, we propose that Yarbus's various research lines are instead deeply and intrinsically interconnected, as are the small eye movements produced during visual fixation and the large-scale scanning patterns associated with visual exploration of objects and scenes. Such apparently disparate viewing behaviors may represent the extremes of a single continuum of oculomotor performance that operates across spatial scales when we search the visual world. PMID- 26562908 TI - Attention in Active Vision: A Perspective on Perceptual Continuity Across Saccades. AB - Alfred L. Yarbus was among the first to demonstrate that eye movements actively serve our perceptual and cognitive goals, a crucial recognition that is at the heart of today's research on active vision. He realized that not the changes in fixation stick in memory but the changes in shifts of attention. Indeed, oculomotor control is tightly coupled to functions as fundamental as attention and memory. This tight relationship offers an intriguing perspective on transsaccadic perceptual continuity, which we experience despite the fact that saccades cause rapid shifts of the image across the retina. Here, I elaborate this perspective based on a series of psychophysical findings. First, saccade preparation shapes the visual system's priorities; it enhances visual performance and perceived stimulus intensity at the targets of the eye movement. Second, before saccades, the deployment of visual attention is updated, predictively facilitating perception at those retinal locations that will be relevant once the eyes land. Third, saccadic eye movements strongly affect the contents of visual memory, highlighting their crucial role for which parts of a scene we remember or forget. Together, these results provide insights on how attentional processes enable the visual system to cope with the retinal consequences of saccades. PMID- 26562909 TI - Common Priority Map for Selection History, Reward and Emotion in the Oculomotor System. AB - In natural scenes, many objects compete for visual selection. However, it is not always clear why certain objects win this competition. I will demonstrate that the eye movement system lives in a constant state of competition among different oculomotor programs. This competition is not limited to the competition between the current goals of the observer and salient objects in the environment but incorporates independent influences from memory, reward, and emotional systems. These involuntary and automatic biases often overcome the goal-directed selection and expose severe limits in goal-driven control. There is also a striking similarity in the way that these very different sources of bias activate the oculomotor system and compete for representation. The inputs from various information sources are integrated in the common map in the oculomotor system for the sole purpose of improving the efficiency of oculomotor selection. PMID- 26562910 TI - Visual Percepts in the Cases of Binocular and Monocular Viewing Stabilized Test Objects, Ganzfeld Stimuli, and Prolonged Afterimages. AB - A thorough analysis of the literature on retinal image stabilization, as well as our own experimental data, present evidence that Yarbus's concept, implying inevitable and irreversible fading of a visible image evoked by stabilized retinal stimulus of any size, color, and luminance in 1 to 3 s after its onset, is not valid in a general case. It has been demonstrated that, even with Yarbus's stabilization techniques, the lifetime of visible images varies from fractions of a second to the whole stimulus duration-up to 30 min in our experiments-depending on many factors: monocular or binocular viewing, stimulus parameters, characteristics of subjects, and so forth. The dynamics of perceived images is determined mainly by the processes at the higher levels of the visual system. In the cases of such unusual visual stimuli as stabilized retinal images, it is problematic for the visual brain to find their proper interpretations in terms of everyday natural experience. Usually, the responses of retinal units are determined by three types of coexisting images: (a) the optical projections of external objects, (b) shadows of the blood vessels and other internal eye structures, (c) virtual patterns caused by the traces of previous stimuli. A task of the visual system is to recognize and visualize only external objects separating their projections from all the entoptic images of the two remaining types. To implement separation, visual brain employs a number of approaches--in particular, the eye movements that cause sliding over the retina but only the projection of the external objects. This means that the peculiar phenomena observed in the cases of stabilized retinal images can be determined not by invariability of such stimuli per se but rather by the fact that stabilization eliminates a powerful cue helping to identify the retinal images belonging to the external objects, thereby increasing the probability to treat them as the entoptic ones which should be ignored or canceled rather than perceived. However, the probability of canceling--image fading--can be essentially reduced in conditions of concordant, large, bright, and sharp binocular stimuli. PMID- 26562911 TI - Yarbus's Conceptions on the General Mechanisms of Color Perception. AB - In the last series of papers published during 1975 to 1980, Alfred Yarbus tried to formulate general conceptions concerning the basic principles of retinal image processing in the human visual system. The original ideas of Yarbus were based on the results of his numerous and various experiments carried out with extraordinary inventiveness and great skill. Being concentrated primarily on the problems of color vision, Alfred Yarbus dreamed of elaborating a comprehensive model that would simulate visual information processing at the monocular precognitive level in the visual system of humans with normal trichromatic color perception. In this article, the most important of Yarbus' experimental paradigms, findings, statements, and conclusions are systematized and considered in relation to the classical theories of color perception and, in particular, fundamental theses of the Nyberg school. The perceptual model developed by Alfred Yarbus remained incomplete. Nevertheless, it is already evident that some intrinsic contradictions make it inadequate in terms of comprehensive modeling. However, certain partial advantages deserve more thorough appreciation and further investigation. PMID- 26562912 TI - Transformation of the Visual Afterimage Under Subject's Eye and Body Movements and the Visual Field Constancy Mechanisms. AB - Two types of positive afterimages differing in their structural complexity- called poor and rich--were used to investigate the visual field constancy mechanisms during eye and head movements. In the case of a poor afterimage, consistent with Emmert's law, every eye and head movement caused the afterimage to appear moving (in exactly the same way), unlike a real object, which appeared to remain stationary during those same eye and head movements (although its retinal image moved opposite to the eye movement). However, in the case of a rich afterimage, the afterimage appeared stationary during eye movements, while a small stationary test light in the real space appeared to move, violating Emmert's law. It is suggested that, in these two cases, the different apparent transformations reflected functioning of different constancy mechanisms. Both mechanisms implement projection of retinal images upon a hypothetical constant visual screen in strict accordance with the subject's movements but in two different ways. The experiments have indicated that, during binocular fusion, the visual afferent system is able to use information from the structural organization of the visual flow to implement the visual field stability and to calculate gaze direction independently of proprioceptive signals. PMID- 26562913 TI - 1-D Vision: Encoding of Eye Movements by Simple Receptive Fields. AB - Eye movements (eyeM) are an essential component of visual perception. They allow the sampling and scanning of stationary scenes at various spatial scales, primarily at the scene level, via saccades, and at the local level, via fixational eyeM. Given the constant motion of visual images on the retina, a crucial factor in resolving spatial ambiguities related to the external scene is the exact trajectory of eyeM. We show here that the trajectory of eyeM can be encoded at high resolution by simple retinal receptive fields of the symmetrical type. We also show that such encoding can account for motion illusions such as the Ouchi illusion. In addition, encoding of motion projections along horizontal and vertical symmetrical simple retinal receptive fields entails a kind of Cartesian decomposition of the 2-D image into two 1-D projections. PMID- 26562914 TI - Neuronal Representation of 3-D Space in the Primary Visual Cortex and Control of Eye Movements. AB - The aim of this article is to consider the correlations between the structure of the primary visual cortical area V1 and control of coordinated movements of the two eyes. Using the anatomical data available, a schematic map of 3-D space representation in the layer IV of area V1 containing only monocular cells has been constructed. The analysis of this map revealed that binocular neurons of V1, which are formed by convergence of monocular cells, should encode the absolute disparity. Participation of monocular and binocular neurons of V1 in the control of convergence, divergence, and version eye movements is discussed. It is proposed that synchronous contraction of corresponding extraocular muscles of both eyes for vergence might be ensured by duplicated transmission of information from the central part of retina to visual cortex of both hemispheres. PMID- 26562915 TI - Gaze Dynamics in the Recognition of Facial Expressions of Emotion. AB - We studied preferably fixated parts and features of human face in the process of recognition of facial expressions of emotion. Photographs of facial expressions were used. Participants were to categorize these as basic emotions; during this process, eye movements were registered. It was found that variation in the intensity of an expression is mirrored in accuracy of emotion recognition; it was also reflected by several indices of oculomotor function: duration of inspection of certain areas of the face, its upper and bottom or right parts, right and left sides; location, number and duration of fixations, viewing trajectory. In particular, for low-intensity expressions, right side of the face was found to be attended predominantly (right-side dominance); the right-side dominance effect, was, however, absent for expressions of high intensity. For both low- and high intensity expressions, upper face part was predominantly fixated, though with greater fixation of high-intensity expressions. The majority of trials (70%), in line with findings in previous studies, revealed a V-shaped pattern of inspection trajectory. No relationship, between accuracy of recognition of emotional expressions, was found, though, with either location and duration of fixations or pattern of gaze directedness in the face. PMID- 26562916 TI - The Impact of Same- and Other-Race Gaze Distractors on the Control of Saccadic Eye Movements. AB - Two experiments were aimed at investigating whether the implementation of voluntary saccades in White participants could be modulated more strongly by gaze distractors embedded in White versus Black faces. Participants were instructed to make a rightward or leftward saccade, depending on a central directional cue. Saccade direction could be either congruent or incongruent with gaze direction of the distractor face. In Experiment 1, White faces produced greater interference on saccadic accuracy than Black faces when the averted-gaze face and cue onset were simultaneous rather than separated by a 900-ms asynchrony. In Experiment 2, two temporal intervals (50 ms vs. 1,000 ms) occurred between the initial presentation of the face with direct-gaze and the averted-gaze face onset, whereas the averted-gaze face and cue onset were synchronous. A greater interference emerged for White versus Black faces irrespective of the temporal interval. Overall, these findings suggest that saccadic generation system is sensitive to features of face stimuli conveying eye gaze. PMID- 26562917 TI - Relation of Descriptor Completeness and Distinctiveness to Localization of the Most Informative Regions in Images. AB - Allocation of informative regions in images depends on a visual task. We propose two criteria for allocation of informative regions in images considering visual recognition of objects in images using a space-variant foveal filter. The first criterion relates to descriptor completeness. This criterion is formalized as a measure of similarity of an original image to an image reconstructed from foveal filter responses. The second criterion relates to descriptor distinctiveness. This criterion relates to the problem of retrieving discriminative and repeatable features in images of objects. It is formalized as a variation of descriptor elements of different objects within the same class. We reveal that regions of interest produced by these criteria are distributed in the areas of high variety of brightness gradients orientations. PMID- 26562918 TI - Smooth Pursuit in Elderly Adults Studied With Apparent Motion. AB - The variability of smooth pursuit eye movements was studied in a group of healthy subjects for horizontal apparent motion by a method that does not require direct measurements of eye movements. It was found that the individual smooth pursuit efficiencies for binocular perception in group of healthy elderly subjects (mean age 61 years) as well as in the group of healthy young adults were distinctly differentiated. Furthermore, we have not detected any age-related decrease in the fraction of subjects showing high smooth pursuit efficiencies. This fact demonstrates that the human oculomotor system is relatively resistant to the effects of aging. At the same time, an appreciable increase of percentage of persons with directional asymmetry of smooth pursuit has been found among elderly adults. A higher smooth pursuit efficiency was noticed reliably more often in the direction from left to right rather than in the opposite direction. Subject eye movements were recorded with i-View XTM Hi-Speed 1250 eye tracking system (SMI Inc.). These records confirmed that the smooth pursuit accuracy of older adults is less than that of young persons, at least in some directions of tracking. PMID- 26562919 TI - Early Changes in Saccadic Eye Movement in Hemiparkinsonian MPTP-Treated Monkeys. AB - The saccadic eye movements declining given the development of Parkinson's disease (PD) still deserves thorough analysis. Recent studies confirmed that PD patients show poor saccadic control in visuomotor tasks. The purpose of this study was to investigate the dynamics of saccades parameters at the development of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. The gradual decline of saccadic control was studied in two monkeys that executed the visuomotor task with low doses of MPTP being injected at a prolonged period of time. The experiment included investigating the horizontal, vertical, oblique visually guided saccades as well as the corrective saccades triggered by stimuli onset in various loci within a two-dimensional visual field in the Gap-Step-Overlap paradigm. Our study revealed that the execution of visually guided saccades with small amplitude and corrective saccades changed dramatically with MPTP-model progressing. These changes are also confirmed statistically at the presymptomatic stage of MPTP syndrome. Not only our study gives a robust report of PD dynamics development and saccadic control but the obtained data could also be helpful in developing methods for the early diagnosis of PD. PMID- 26562920 TI - Scanpaths of Complex Image Viewing: Insights From Experimental and Modeling Studies. AB - From the first works of Buswell, Yarbus, and Noton and Stark, the scan path for viewing complex images has been considered as a possible key to objective estimation of cognitive processes and their dynamics. However, evidences both pro and con were revealed in the modern research. In this article, the results supporting the Yarbus-Stark concept are presented. In psychophysical tests, two types of images (three paintings from Yarbus' works and four textures) were used with two instructions, namely, "free viewing" and "search for modified image regions." The focus of the analysis of experimental results and modeling has been given to local elements of the scan path. It was shown that each parameter used (square of viewing area, S; distance between center of mass of viewing area and image center, R; parameter Xi, based on duration of the current fixation and angle between preceding and following saccades), reflects the specificity of both visual task and image properties. Additionally, the return gaze fixations which have a set of specific properties and mainly address to the areas of interest on image were revealed. Evidently these facts can be formalized in an advanced mathematical model as additional instrument to study the mechanisms of complex image viewing. PMID- 26562921 TI - The Influence of Monocular Spatial Cues on Vergence Eye Movements in Monocular and Binocular Viewing of 3-D and 2-D Stimuli. AB - The influence of monocular spatial cues on the vergence eye movements was studied in two series of experiments: (I) the subjects were viewing a 3-D video and also its 2-D version-binocularly and monocularly; and (II) in binocular and monocular viewing conditions, the subjects were presented with stationary 2-D stimuli containing or not containing some monocular indications of spatial arrangement. The results of the series (I) showed that, in binocular viewing conditions, the vergence eye movements were only present in the case of 3-D but not 2-D video, while in the course of monocular viewing of 2-D video, some regular vergence eye movements could be revealed, suggesting that the occluded eye position could be influenced by the spatial organization of the scene reconstructed on the basis of the monocular depth information provided by the viewing eye. The data obtained in series (II), in general, seem to support this hypothesis. PMID- 26562922 TI - A Relationship Between Visual Complexity and Aesthetic Appraisal of Car Front Images: An Eye-Tracker Study. AB - Image aesthetic pleasure (AP) is conjectured to be related to image visual complexity (VC). The aim of the present study was to investigate whether (a) two image attributes, AP and VC, are reflected in eye-movement parameters; and (b) subjective measures of AP and VC are related. Participants (N=26) explored car front images (M=50) while their eye movements were recorded. Following image exposure (10 seconds), its VC and AP were rated. Fixation count was found to positively correlate with the subjective VC and its objective proxy, JPEG compression size, suggesting that this eye-movement parameter can be considered an objective behavioral measure of VC. AP, in comparison, positively correlated with average dwelling time. Subjective measures of AP and VC were related too, following an inverted U-shape function best-fit by a quadratic equation. In addition, AP was found to be modulated by car prestige. Our findings reveal a close relationship between subjective and objective measures of complexity and aesthetic appraisal, which is interpreted within a prototype-based theory framework. PMID- 26562923 TI - Metaphorical Salience in Artistic Text Processing: Evidence From Eye Movement. AB - The study aimed to explore processing difference between a literal phrase and a metaphoric one. Unlike artificially created stimuli in most experimental research, an artistic text with an ambiguous binary metaphoric phrase was used. Eye tracking methodology was applied. Results suggested difference between the two types of phrases in both early and late processing measures. PMID- 26562924 TI - Eye Movements as Indicators of Vestibular Dysfunction. AB - Virtual reality technologies are in wide use in sport psychology. An advantage of this kind of technology is the possibility to assess sportspeople's readiness to perform complex movements. This study is aimed at developing a method for the evaluation of vestibular function disturbances in young skaters. Such disturbances may occur while skaters are performing rotation movements. To achieve this goal, we induced a vection illusion, accompanied by virtual environment rotation in a CAVE virtual reality system. Vestibular disturbances were tested for two groups-professional skaters and people who had very little or no skating experience. The quantitative evaluation of vestibular dysfunction was based on eye movement characteristics, which were recorded in subjects experiencing a vection illusion. PMID- 26562925 TI - Monocular Versus Binocular Calibrations in Evaluating Fixation Disparity With a Video-Based Eye-Tracker. AB - When measuring fixation disparity (an oculomotor vergence error), the question arises as to whether a monocular or binocular calibration is more precise and physiologically more appropriate. In monocular calibrations, a single eye fixates on a calibration target that is taken as having been projected onto the center of the fovea; the corresponding vergence state represents the heterophoria (the resting vergence position), which has no effect on the calibration procedure. In binocular calibrations, a vergence error may be present and may affect the subsequent measurement of the fixation disparity during binocular recordings. This study includes a test of the precision of both monocular and binocular calibrations and an evaluation of the impact of the calibration procedure on the measurement of fixation disparity during a dot scanning task. Our results show that 11 participants (out of 19) each exhibited a significant difference in fixation disparity with the two types of calibration procedures. In addition, the fixation disparity was more strongly affected by heterophoria undergoing monocular calibration, as opposed to binocular calibration. This serves as additional evidence showing that the monocular calibration produces a physiologically more plausible fixation disparity and seems to be more appropriate for studying the full extent of fixation disparity. PMID- 26562926 TI - ETRAN--R Extension Package for Eye Tracking Results Analysis. AB - Novel open source R extension package for general-purpose eye tracking results analysis proposed. Now supported features are data loading from SMI eye trackers, different methods of fixations detection, various imaging techniques for raw data, and detected fixations (time sequence, scanpath, heatmap, and dynamic visualization). The modular structure of the package and a detailed description of each function provide a convenient way to further extend the functionality. Effective use of package requires knowledge of R programming language and environment. PMID- 26562927 TI - The Effectiveness of Gaze-Contingent Control in Computer Games. AB - Eye-tracking technology and gaze-contingent control in human-computer interaction have become an objective reality. This article reports on a series of eye tracking experiments, in which we concentrated on one aspect of gaze-contingent interaction: Its effectiveness compared with mouse-based control in a computer strategy game. We propose a measure for evaluating the effectiveness of interaction based on "the time of recognition" the game unit. In this article, we use this measure to compare gaze- and mouse-contingent systems, and we present the analysis of the differences as a function of the number of game units. Our results indicate that performance of gaze-contingent interaction is typically higher than mouse manipulation in a visual searching task. When tested on 60 subjects, the results showed that the effectiveness of gaze-contingent systems over 1.5 times higher. In addition, we obtained that eye behavior stays quite stabile with or without mouse interaction. PMID- 26562929 TI - Enhancement on Wingate Anaerobic Test Performance With Hyperventilation. AB - Relatively long-lasting metabolic alkalizing procedures such as bicarbonate ingestion have potential for improving performance in long-sprint to middle distance events. Within a few minutes, hyperventilation can induce respiratory alkalosis. However, corresponding performance effects are missing or equivocal at best. PURPOSE: To test a potential performance-enhancing effect of respiratory alkalosis in a 30-s Wingate Anaerobic Test (WAnT). METHODS: 10 men (mean +/- SD age 26.6 +/- 4.9 y, height 184.4 +/- 6.1 cm, body-mass test 1 80.7 +/- 7.7 kg, body-mass test 2 80.4 +/- 7.2 kg, peak oxygen uptake 3.95 +/- 0.43 L/min) performed 2 WAnTs, 1 with and 1 without a standardized 15-min hyperventilation program pre-WAnT in randomized order separated by 1 wk. RESULTS: Compared with the control condition, hyperventilation reduced (all P < .01) pCO2 (40.5 +/- 2.8 vs 22.5 +/- 1.6 mm Hg) and HCO3 - (25.5 +/- 1.7 vs 22.7 +/- 1.6 mmol/L) and increased (all P < .01) pH (7.41 +/- 0.01 vs 7.61 +/- 0.03) and actual base excess (1.4 +/- 1.4 vs 3.2 +/- 1.6 mmol/L) pre-WAnT with an ergogenic effect on WAnT average power (681 +/- 41 vs 714 +/- 44 W) and total metabolic energy (138 +/- 12 vs. 144 +/- 13 kJ) based on an increase in glycolytic energy (81 +/- 13 vs 88 +/- 13 kJ). CONCLUSION: Hyperventilation-induced respiratory alkalosis can enhance WAnT cycling sprint performance well in the magnitude of what is seen after successful bicarbonate ingestion. PMID- 26562930 TI - Self-Myofascial Release: No Improvement of Functional Outcomes in 'Tight' Hamstrings. AB - PURPOSE: Self-myofascial release (SMR) is a common exercise and therapeutic modality shown to induce acute improvements in joint range of motion (ROM) and recovery; however, no long-term studies have been conducted. Static stretching (SS) is the most common method used to increase joint ROM and decrease muscle stiffness. It was hypothesized that SMR paired with SS (SMR+SS) compared with SS alone over a 4-wk intervention would yield greater improvement in knee-extension ROM and hamstring stiffness. METHODS: 19 men (22 +/- 3 y) with bilateral reduced hamstring ROM had each of their legs randomly assigned to either an SMR+SS or an SS-only group. The intervention consisted of 4 repetitions of SS each for 45 s or the identical amount of SS preceded by 4 repetitions of SMR each for 60 s and was performed on the respective leg twice daily for 4 wk. Passive ROM, hamstring stiffness, rate of torque development (RTD), and maximum voluntary contraction (MVC) were assessed pre- and postintervention. RESULTS: Passive ROM (P < .001), RTD, and MVC (P < .05) all increased after the intervention. Hamstring stiffness toward end-ROM was reduced postintervention (P = .02). There were no differences between the intervention groups for any variable. CONCLUSION: The addition of SMR to SS did not enhance the efficacy of SS alone. SS increases joint ROM through a combination of decreased muscle stiffness and increased stretch tolerance. PMID- 26562932 TI - [Reading as identity and/or companion. Reflections on the ontology of the rubric "Polcmustra" (Bookshelf Survey)]. PMID- 26562931 TI - Expression of SERPINA3s in cattle: focus on bovSERPINA3-7 reveals specific involvement in skeletal muscle. AB - alpha1-Antichymotrypsin is encoded by the unique SERPINA3 gene in humans, while it is encoded by a cluster of eight closely related genes in cattle. BovSERPINA3 proteins present a high degree of similarity and significant divergences in the reactive centre loop (RCL) domains which are responsible for the antiprotease activity. In this study, we analysed their expression patterns in a range of cattle tissues. Even if their expression is ubiquitous, we showed that the expression levels of each serpin vary in different tissues of 15-month-old Charolais bulls. Our results led us to focus on bovSERPINA3-7, one of the two most divergent members of the bovSERPINA3 family. Expression analyses showed that bovSERPINA3-7 protein presents different tissue-specific patterns with diverse degrees of N-glycosylation. Using a specific antibody raised against bovSERPINA3 7, Western blot analysis revealed a specific 96 kDa band in skeletal muscle. BovSERPINA3-7 immunoprecipitation and mass spectrometry revealed that this 96 kDa band corresponds to a complex of bovSERPINA3-7 and creatine kinase M-type. Finally, we reported that the bovSERPINA3-7 protein is present in slow-twitch skeletal myofibres. Precisely, bovSERPINA3-7 specifically colocalized with myomesin at the M-band region of sarcomeres where it could interact with other components such as creatine kinase M-type. This study opens new prospects on the bovSERPINA3-7 function in skeletal muscle and promotes opportunities for further understanding of the physiological role(s) of serpins. PMID- 26562933 TI - Experience-dependent emergence of a grouping bias. AB - Humans share with non-human animals perceptual biases that might form the basis of complex cognitive abilities. One example comes from the principles described by the iambic-trochaic law (ITL). According to the ITL, sequences of sounds varying in duration are grouped as iambs, whereas sequences varying in intensity are grouped as trochees. These grouping biases have gained much attention because they might help pre-lexical infants bootstrap syntactic parameters (such as word order) in their language. Here, we explore how experience triggers the emergence of perceptual grouping biases in a non-human species. We familiarized rats with either long-short or short-long tone pairs. We then trained the animals to discriminate between sequences of alternating and randomly ordered tones. Results showed animals developed a grouping bias coherent with the exposure they had. Together with results observed in human adults and infants, these results suggest that experience modulates perceptual organizing principles that are present across species. PMID- 26562934 TI - Mates but not sexes differ in migratory niche in a monogamous penguin species. AB - Strong pair bonds generally increase fitness in monogamous organisms, but may also underlie the risk of hampering it when re-pairing fails after the winter season. We investigated whether partners would either maintain contact or offset this risk by exploiting sex-specific favourable niches during winter in a migratory monogamous seabird, the southern rockhopper penguin Eudyptes chrysocome. Using light-based geolocation, we show that although the spatial distribution of both sexes largely overlapped, pair-wise mates were located on average 595 +/- 260 km (and up to 2500 km) apart during winter. Stable isotope data also indicated a marked overlap between sex-specific isotopic niches (delta13C and delta15N values) but a segregation of the feeding habitats (delta13C values) within pairs. Importantly, the tracked females remained longer (12 days) at sea than males, but all re-mated with their previous partners after winter. Our study provides multiple evidence that migratory species may well demonstrate pair-wise segregation even in the absence of sex-specific winter niches (spatial and isotopic). We suggest that dispersive migration patterns with sex-biased timings may be a sufficient proximal cause for generating such a situation in migratory animals. PMID- 26562935 TI - Invasive ants carry novel viruses in their new range and form reservoirs for a honeybee pathogen. AB - When exotic animal species invade new environments they also bring an often unknown microbial diversity, including pathogens. We describe a novel and widely distributed virus in one of the most globally widespread, abundant and damaging invasive ants (Argentine ants, Linepithema humile). The Linepithema humile virus 1 is a dicistrovirus, a viral family including species known to cause widespread arthropod disease. It was detected in samples from Argentina, Australia and New Zealand. Argentine ants in New Zealand were also infected with a strain of Deformed wing virus common to local hymenopteran species, which is a major pathogen widely associated with honeybee mortality. Evidence for active replication of viral RNA was apparent for both viruses. Our results suggest co introduction and exchange of pathogens within local hymenopteran communities. These viral species may contribute to the collapse of Argentine ant populations and offer new options for the control of a globally widespread invader. PMID- 26562936 TI - Ocean acidification bends the mermaid's wineglass. AB - Ocean acidification lowers the saturation state of calcium carbonate, decreasing net calcification and compromising the skeletons of organisms such as corals, molluscs and algae. These calcified structures can protect organisms from predation and improve access to light, nutrients and dispersive currents. While some species (such as urchins, corals and mussels) survive with decreased calcification, they can suffer from inferior mechanical performance. Here, we used cantilever beam theory to test the hypothesis that decreased calcification would impair the mechanical performance of the green alga Acetabularia acetabulum along a CO2 gradient created by volcanic seeps off Vulcano, Italy. Calcification and mechanical properties declined as calcium carbonate saturation fell; algae at 2283 uatm CO2 were 32% less calcified, 40% less stiff and 40% droopier. Moreover, calcification was not a linear proxy for mechanical performance; stem stiffness decreased exponentially with reduced calcification. Although calcifying organisms can tolerate high CO2 conditions, even subtle changes in calcification can cause dramatic changes in skeletal performance, which may in turn affect key biotic and abiotic interactions. PMID- 26562937 TI - Coronary angiogenesis during morphine and nicotine withdrawal in two-kidney one clip hypertensive (2K1C) rats. AB - OBJECTIVE: This study was aimed to investigate the effects of addiction to nicotine and morphine and their withdrawal on coronary angiogenesis and serum NO concentrations in two-kidney one-clip hypertensive (2K1C) rats. METHODS: Male hypertensive rats were divided into the two below groups: Group (1): Rats received saline for 8 weeks (N=8); Group (2): Rats received morphine and nicotine for 8 weeks (n=32). At the end of 8 weeks, the groups (2) were divided into the four sub-groups, which three of them were treated with withdrawal drugs. Following treatments, blood pressure, heart rate, plasma renin activity (PRA), NO concentration and capillary density were measured. RESULTS: Results showed that blood pressure was significantly reduced in the addicted group when compared to non-addicted (p<0.05). The withdrawal completely reversed blood pressure to the level observed pre-addiction (p<0.05). Coronary angiogenesis was significantly lower in the addicted group in comparistion to normal (p<0.05) but withdrawal of addiction did not improve angiogenesis. CONCLUSION: On the basis of the present findings, it may be indicative that the risk of cardiovascular complications in addiction is concurrent to chronic hypertension, which shows the importance of early diagnosis and treatment in clinical condition (Fig. 4, Ref. 59). PMID- 26562938 TI - [Sense making affects stress response processes in parents of children with developmental disorders]. AB - This study examined the stress-buffering effects of sense making among parents of children with developmental disorders. A model assuming that social support is related to sense making and that coping strategy mediates sense making and stress response was examined via a questionnaire survey of mothers of children with developmental disorders (N = 245). The results of structural equation modeling analysis suggested the following: (a) the stress-buffering effects of sense making were mediated through an emotional approach coping strategy and sense making was positively related to stress response mediated through an active coping strategy; (b) seeking a meaning directly increased one's stress response, which was indirectly mediated by an avoidant coping strategy; and (c) the effects of social support on sense making and coping strategy, as well as stress response, varied with the kind of social resources from whom mothers anticipated support. These results suggest that sense making affects stress response in mothers of children with developmental disorders through the social support they anticipate and the coping strategies they adopt. PMID- 26562940 TI - [The effects of self-anger on rumination and on mental health]. AB - This study investigated the effects of self-anger on rumination and mental health (depression and anxiety). In study 1, a scale to measure self-anger was developed by the review of previous studies and survey interviews. Exploratory factor analysis identified one factor of self-anger. The reliability and validity of the scale were confirmed by internal consistency measures and correlations with other anger-related scales. In study 2, which used the self-anger scale developed in study 1, undergraduate and graduate students completed a set of scales to measure self-anger, rumination, depression, anxiety, and five-factor personality traits. The results of mediation analysis indicated that self-anger effects depression and anxiety directly or through mediating rumination excluding the effect of sex and neuroticism. Finally, the possibility that self-anger management leads to the reduction of rumination and improvement of mental health was discussed. PMID- 26562939 TI - [Examination of role of personality and the effects of stress coping in stress process as within process]. AB - This study used daily diary methods to investigate if fear of interpersonal stress in daily affect could be explained by coping strategies, and if daily affect and coping would vary randomly across personality traits. Every day for one week, 103 undergraduates recorded their daily events, perceived interpersonal stress, cognitive appraisal, coping strategies, positive events, and positive and negative affect twice a day. A hierarchical linear model and multilevel structural equation modeling were used to examine the relationships between variables. Results, suggest that problem-focused coping was associated with within-level maladjustment, while positive reappraisal was associated with within level adjustment. In addition, neuroticism appeared to moderate the relationship between coping and daily affect. Furthermore, there is evidence that higher fear of interpersonal stress predicts greater active coping, and positive affect. PMID- 26562941 TI - [The development, reliability, and validity of a Japanese version of the MBI-ES]. AB - In this study, we developed a Japanese version of the Maslach Burnout Inventory - Educators Survey (MBI-ES). We also examined the reliability and validity of the scale, based on data from Japanese schoolteachers. Because some items related to depersonalization showed a floor effect, the reliability of the MBI-ES was evaluated using item response theory (IRT), which can evaluate the difficulty of the items. The IRT analysis showed that scores of emotional exhaustion and personal accomplishment had high reliabilities among the wide range of distribution of the latent scores around the means. However, the reliability of the depersonalization items was estimated to be moderate when it was implemented among highly depersonalized teachers, whereas the reliability was lower for relatively healthy teachers. Correlations with the General Health Questionnaire, frequency of emotional labor, and job satisfaction were mostly consistent with previous research and the current theory of burnout, supporting the high validity of the Japanese version of the MBI-ES. PMID- 26562942 TI - [Do adults' pretense signals promote pretend play behavior in children?]. AB - Our goal in this study was to examine whether controlled pretense signal presentation by an adult promoted pretend play behavior in toddlers. Seventy-two Japanese toddlers (24 toddlers in the 18-month-old group, 24 toddlers in the 24 month-old group, and 24 toddlers in the 30-month-old group) participated in one of two experimental conditions: signal and signal-less. In the signal condition, the experimenter presented children with pretend play behaviors (eating, drinking, pouring, and wiping) accompanied by a smile, speech including sound effects, and gazing. In the signal-less condition, the experimenter presented only pretend play behavior with a neutral facial expression without speech or gazing. For each child, we coded the number of pretend play behaviors and recorded the number of seconds the toddler engaged in the behavior. Results indicated that 18- and 24-month-old toddlers' pretend play behavior lasted longer in the signal condition than it did in the signal-less condition. However, the 30 month-old toddlers showed no difference in pretend play behaviors between the signal conditions. In sum, adults' pretense signals promoted pretend play behavior only in 18- and 24-month-olds, and not in 30-month-olds. PMID- 26562943 TI - [Remembering past events activates temporal concepts of future]. AB - The cognitive function to project oneself into the specific past or future is labeled mental time travel (MTT). MTT to the past is considered "episodic memory" and the future is termed "episodic future thinking". Remembering the past and imaging the future during MTT both draw on information stored in episodic memory: a process that enables integration of episodic information into a coherent event representation. Recent studies suggested that episodic information in past/future event representations varies with temporal distance from the present to the event. However, it is unclear whether the influence on temporal distance is actually caused by the function of episodic memory retrieval. The present study investigated the relationship between episodic memory and temporal concepts with a lexical decision task. The results indicate that remembering the past activated temporal concepts of the near future more than that of the far future. This finding suggests that the rich information derived from episodic memory modulates the subjective sense of time in episodic future thinking. PMID- 26562944 TI - [The effect of self-reflection on depression mediated by hardiness]. AB - Previous studies have shown that two types of private self-consciousness result in opposing effects on depression; one of which is self-rumination, which leads to maladaptive effect, and the other is self-reflection, which leads to an adaptive effect. Although a number of studies have examined the mechanism of the maladaptive effect of self-rumination, only a few studies have examined the mechanism of the adaptive effect of self-reflection. The present study examined the process of how self-reflection affected depression adaptively, Based on the previous findings, we proposed a hypothetical model assuming that hardiness acts as a mediator of self-reflection. To test the validity of the model, structural equation modeling analysis was performed with the cross-sectional data of 155 undergraduate students. The results. suggest that the hypothetical model is valid. According to the present results and previous findings, it is suggested that self-reflection is associated with low levels of depression and mediated by "rich commitment", one component of hardiness. PMID- 26562945 TI - [The psychological effects of taking in "Shikohin": A cross-sectional exploratory study]. AB - This study explores the psychological effects that Japanese people experience when consuming their "Shikohin", such as alcohol, tea, coffee, and tobacco. We'conducted a cross-sectional study among 542 people, from 20-to 69-year-old; who regularly consumed any one of "Shikohin" in Tokyo, Kanagawa, Saitama, and Chiba. The participants responded to an anonymous questionnaire concerning the consumption patterns of their "Shikohin" and the psychological effects that they experienced in taking in their "Shikohin". Results obtained using the K-J methods showed three common psychological effects in each "Shikohin". These effects included an increase in relaxation response, the promotion of social relationships, and an increase in positive mood. Our findings suggest that Japanese people may get some common effects through consumption of different "Shikohin". PMID- 26562946 TI - [Test-retest reliability of the Implicit Association Test for measuring shyness: Inclusion of malleability of implicit shyness]. AB - The Implicit Association Test of Shyness (Shyness IAT: Aikawa & Fujii, 2011) provides an indirect assessment of shyness by measuring associations of self (vs. other) with shyness-related (vs sociability-related) words. In this study we examined the test-retest reliability of the Shyness IAT. Thirty-five participants responded twice to the Shyness IAT with a time lag of one month. The correlation coefficient between the two time points was .54 (p = .001), confirming an adequate level of test-retest reliability. Indeed, changes in explicit and implicit shyness between the two time points were not related to sociable behavior during the one month period. Implications of the results for the assessment of personalities using IATs as well as relevant future directions are discussed. PMID- 26562947 TI - [The development of the Five-item Loneliness Scale for Children]. AB - The purpose of the present study was to develop a simplified scale to assess loneliness in children. Participants were 646 elementary school students (335 boys and 311 girls) from 4th to 6th grade and 24 homeroom teachers who identified lonely children within the participants of their classes. The'student participants completed the Five-item Loneliness Scale for Children (Five-LSC) and other scales measuring social skills, social competence, and withdrawal to confirm the validity of the Five-LSC. The results showed that the Five-LSC was both reliable and valid. In addition, there were no grade or sex differences in loneliness. Future research using the Five-LSC was discussed. PMID- 26562948 TI - Terms to Be Concerned About in EMR Purchasing / Financing Contracts. PMID- 26562949 TI - Michigan Care Improvement Registry Update. PMID- 26562950 TI - Breaking Up Is Hard to Do, But It's Time to Move On. PMID- 26562951 TI - The Cost of Technology: Facing the Challenge. PMID- 26562952 TI - Telemedicine: Emerging Risks. PMID- 26562953 TI - Has Technology Made You Richer? PMID- 26562954 TI - What Is the Wealth of Technology Affording Us? PMID- 26562955 TI - Addressing the Remaining Challenge of Pneumococcal Disease in Older Adults. PMID- 26562956 TI - Pneumococcal Disease in Older Adults--An Overview. PMID- 26562957 TI - Challenges in the Management of Pneumococcal Disease in Older Adults. PMID- 26562958 TI - Age and the Immune System. PMID- 26562959 TI - Vaccines for the Prevention of Pneumococcal Disease. PMID- 26562960 TI - Pneumococcal Vaccines--a Real World Perspective. PMID- 26562961 TI - Pneumococcal Vaccination in Different Specialties. PMID- 26562962 TI - Role of Pneumococcal Vaccination in Chronic Lung Diseases. PMID- 26562963 TI - Pneumococcal Vaccine in Diabetes: Relevance in India. AB - Currently we have more than 65 million Diabetes patients in India with estimated 80 million prediabetics. Diabetes is a immunologically vulnerable population to develop all types of microbial infections. Pneumoccocal infections do have a substantial morbidity and mortality burden in the community. India has a large geriatric pool now which has substantially increased pneumococcal disease burden. Diabetes is a well-known risk factor for pneumococcal infection and predisposes individuals to nasopharyngeal colonization with the pneumococcus which is associated with invasive infection. In diabetics who are elderly, with chronic kidney or pulmonary disease and long standing duration of the disease with poor glycemic control are the highest risk group susceptible to invasive pneumococcal disease. With now availibilty of Pneumoccal vaccine in India, now it may be an preventive option which can be offered. Most global organisations recommend pneumococcal vaccination to diabetics. PMID- 26562964 TI - Role of Pneumococcal Vaccination in Renal Diseases. PMID- 26562965 TI - Role of Pneumococcal Vaccination in Oncology Patients. PMID- 26562966 TI - Pneumococcal Vaccination in Rheumatic Diseases. PMID- 26562967 TI - Role of Pneumococcal Vaccine in HIV Infected Population. PMID- 26562968 TI - Role of Pneumococcal Vaccine in Travelers. PMID- 26562969 TI - An educational approach for "non-compliant" patients. AB - Patients frequently are readmitted to the intensive care unit because of a lack of lifestyle change that puts them at risk for cardiac issues. Nurses view this as non-compliance, however, use of the term "non-compliance" has negative connotations. The factors contributing to non-compliance include nursing's views, and patients' perceptions of health risk and lack of motivation. In this article, the author proposes an educational approach and strategies for intensive care nurses to use when teaching patients about changes required to address lifestyle behaviours, such as increasing exercise, smoking cessation, and healthy diets. PMID- 26562970 TI - Checklist to meet Ethical and Legal Obligations in the consent pathway for critically ill patients (ChELO): A quality improvement project and case studies. AB - Ethical or legal errors related to the consent pathway for incapable patients are an everyday reality. Quality improvements in communication or palliative care have been attempted, but little attention has been given to meeting basic legal and ethical obligations. In this paper, the authors share lessons learned during two years of implementing the Checklist for meeting Ethical and Legal Obligations (ChELO) in the intensive care unit of a large community hospital in Ontario. We use a case-based approach to demonstrate the need for our intervention, our use of positive deviance in a change strategy, and the effectiveness of the checklist itself. Through stories, we show common ethical and legal errors related to the consent pathway and how we were able to resolve them with this innovative tool. PMID- 26562971 TI - Approach to unplanned extubations in a pediatric intensive care unit. AB - An unplanned extubation is defined as an extubation that occurs at a time other than that planned for the procedure. It may result in life-threatening complications such as laryngospasm, pulmonary or cardiac failure. Quality improvement initiatives have targeted an unplanned extubation rate of 0% in pediatric intensive care units. OBJECTIVE: To determine if a targeted approach specific to local practices and unit culture could decrease the incidence of and, ultimately, eliminate unplanned extubations in our tertiary care PICU. METHOD: This study used a mixed methods design involving three phases. Phase 1 involved the retrospective collection of data on all unplanned extubations from September 2011 to August 2013. Phase 2 involved development of a quality improvement program and Phase 3 involved prospective collection of data on all unplanned extubations from January to August 2014. RESULTS: There were 12 unplanned extubations in Phase 1 resulting in a rate of 0.9 per 100 patient ventilator days. The majority of unplanned extubations occurred in children less than one year of age (66.6%, 8/12), and during the nightshift (91.7%). In addition, 25% of events occurred during chest radiographs. Forty-one per cent of patients who had an unplanned extubation required re-intubation and one of the seven children who remained extubated required non-invasive airway support. Staff concerns included inadequate sedation, loose endotracheal tubes and frequent manipulation of endotracheal tubes. Following Phase 2 and a more comprehensive tracking method, we recorded 10 unplanned extubations with a rate of 0.9 per 100 patient ventilator days, but there were no unplanned extubations in patients less than a month of age or during chest radiographs and only four unplanned extubations occurred during the nightshift (40%). CONCLUSION: Our initiatives were successful in decreasing the unplanned extubations associated with certain high-risk factors in our unit, but not in decreasing our overall unplanned extubation rate. We have identified several issues to target for our next round of audit and feedback. While it is important to learn from studies that show a decrease in unplanned extubation rates, we think that it is equally important to understand why others do not achieve their desired goals, as these studies may provide support and ideas for other units struggling with the same issues. PMID- 26562973 TI - Fundamental changes occurring in the dental delivery system in this country. PMID- 26562972 TI - Every Pinohc Should Count. PMID- 26562974 TI - "Corporate dental practice" really mean? PMID- 26562975 TI - Future of dental practice. PMID- 26562976 TI - A Short Tour as a Staff Dentist in a Large Group Practice. AB - A large group practice can be owned and managed by a dentist with all business operations internal to the organization. Under such a system there can still be a separation of chairside and overall patient oral health considerations. Such a model provides benefits to some dentists--specially those beginning their careers and those who are working a few hours per week at the end of their careers. Centralizing business functions within an office and screening them from the practitioners who provide the care have advantages and disadvantages. PMID- 26562977 TI - Practice Experience with a Practice Management Company. AB - This article describes the experiences of a dentist using a contracted dental services organization to manage the business aspects of a multisite group oral and maxillofacial practice. The need for help with management functions first became apparent in medicine, and several models emerged there. The model used in this practice sought to take advantage of specialized expertise without reducing practitioners' control over dental decisions, including those going beyond narrow clinical decisions. Personal experiences and suggestions for best fit between practices on contracted services are presented. PMID- 26562978 TI - A Comprehensive Health Group Practice Model. AB - Permanente Dental Associates includes 17 offices in the Pacific Northwest. Among the distinguishing characteristics of this model are a predominantly HMO structure and integration of care in a general medical program. Staff dentists are on salary and are largely relieved of the business details of practice. Ultimate control of the system is vested in a group of shareholders--the dentists who practice chairside. One of the shareholder-practitioners discusses his perspective on this system. PMID- 26562979 TI - The Indian Health Service Model From the Treatment Perspective. AB - The nonprofit dental delivery model is appropriate for the needs of specific patient populations. The Indian Health Service is an example of how care can be provided where traditional fee-for-service and indemnity mechanisms may be insufficient. Separating care from management in this context gives dentists greater power over individual treatment decisions, increased choice of patient relevant care options, and control over development of the practice model and its evolution. The needs of various populations groups and the funding or profit model inevitably influence the composition of the dental team and assignment of dental duties. PMID- 26562980 TI - Retrospective Evaluation of Treatment Planning for Dental Implant. AB - This retrospective study investigates the diagnostic rationale for the extraction of teeth and their replacement with implants in a dental school setting. Most of the teeth were extracted for restorative reasons (62.7%). The other reasons for extraction were periodontal (35.1%) and endodontic (1.3%). A panel of endodontists disagreed with the treatment-planning dentists' decisions in 40.3% of the cases. Slightly more than half, 52.9%, of the disagreements were for restorative reasons. Most of the decisions in disagreement were made by general dentists (60.6%), far fewer by prosthodontists (25.5%), periodontists (12.2%), and oral surgeons (1.6%). An extensive review of the literature is provided. PMID- 26562981 TI - Do Patients and Dentists See Ethics the Same Way? AB - The most common approach to ethics in dentistry and bioethics generally is through principles. To be effective, principles must be interpreted in particular situations, and the skill of interpretation requires many years of practice with feedback. The opinions of 91 dentists and 54 patients regarding multiple potential actions and justifications for these actions were gathered for eight dental ethics cases. The summary responses of dentists and patients have been integrated as feedback in an online ethics education exercise that individual dentists can use (see www.dental ethics.org/idea). The dataset of responses was also analyzed for general findings. It emerged that patients and dentists agree to a substantial extent on the average approaches, but they differ systematically on certain of the details. Some ethical issues stimulated a narrow range of responses while others, especially those of a nonclinical nature were regarded as ambiguous and are thus good candidates for future ethics training. A factor analysis revealed a five-dimension structure underlying dental ethics. Patients are most apt to view dentistry using a lens of oral health outcomes while practitioners prefer to stress the process and the technical dimensions of practice. The largest area of difference was patients' much greater interest in dentists assuming an active role as patient oral health advocates with their colleagues. PMID- 26562982 TI - A pilot study on the application of the current European guidelines for the management of acute coronary syndrome without elevation of ST segment (NSTEMI) in the Emergency Department setting in the Italian region Lazio. AB - BACKGROUND: In 2011 the European Society of Cardiology published the new guidelines for the treatment and management of acute coronary syndrome without elevation of the ST segment (NSTEMI). For the treatment of the syndrome, the use of P2Y12 inhibitors in addition to aspirin was strongly recommended (evidence IA). We studied the application of this recommendation in the setting of the emergency department in the vast and uneven area of the Italian region Lazio, three years after the release of these drugs in Italy. METHODS: 121 consecutive patients (65% older than 65 years) affected by NSTEMI were recruited between May and July 2013. During the transition in the emergency department data was collected on patient's symptoms, syndrome severity and type & timing of treatments chosen. Adherence to the guidelines was evaluated considering the number of "good treated" patients: these being the patients that received at least 80% of the main five recommendations on percutaneous coronary intervention (PCI) timing, antiplatelet and anti-coagulant therapy suggested by the European Cardiology Task Force (ESC guidelines, 2011) for the very acute phase of NSTEMI. RESULTS: Patients were treated with: 1) 35% of cases with double antiplatelet therapy and anticoagulation (DAPT+AC), 2) 22% of cases with single antiplatelet and anticoagulation (SAPT+AC), 3) 6% of cases with a single antiplatelet therapy (SAPT), 4) 6% of cases with a double antiplatelet therapy (DAPT) and 5) 24% of cases did not receive any therapy. Data on PCI was available for 95 patients and, of these, only 82% of the patients underwent the procedure. The percentage of "good treated" patients were among of 20-40%, depending on PCI timing--as guidelines suggested--was considered as mandatory (20,5%) or as the extreme time limit (40%). Significant differences were found between patients treated in a central hospital with a hemodynamic laboratory active 24/24hr (HUB) and patients treated in the other hospital (SPOKE). HUBs showed a higher percent of "good treated" patients, a higher percentage of early invasive treated and a better adherence to recommended pharmacological therapy. CONCLUSIONS: A significant number of patients did not receive adequate treatment during the emergency department stay. The absence of hemodynamic services increases the risk of inadequate treatment. PMID- 26562983 TI - Report on Non-fatal events cardio-cerebro-vascular to ten years in a Southern Italy cohort. AB - BACKGROUND: Data relating to non-fatal cardiovascular events are poor but these data are essential to organize targeted interventions on the territory and to understand their effectiveness. METHODS: We calculated the rates of morbidity from cardiovascular events covering the period 1998/99-2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. RESULTS: The incidence of events to ten years of non-fatal myocardial infarc.ion was 2.2% in men and of 1.8% in women. PCI interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). CONCLUSION: Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in keeping with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis are useful in providing additional information for planning prevention interventions targeted to its own territory. PMID- 26562984 TI - [Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I]. AB - In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we will investigate, micro-RNA, posttranslational modification and microspheres based therapy. PMID- 26562985 TI - [Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure. Part II]. AB - In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. After the evaluation of the results obtained from gene therapy and stem cells, in this part we evaluate micro-RNA, post-translational modification and microspheres based therapy. PMID- 26562987 TI - Usefulness of transthoracic echocardiogram in management of cardiac involvement in large B-Cell lymphoma: a case report. AB - Primary lymphoma often involve the heart, especially the right side. Prompt diagnosis is necessary to start the right therapy and decrease symptoms and death risk rate. Transthoracic echocardiogram is the first line exam to perform when symptoms are suspicious of mediastinal mass. PMID- 26562986 TI - A rare case of acute Clozapine- related thrombogenic myocarditis. PMID- 26562988 TI - [The GICR polls: a new instrument for Cardiovascular Prevention and Rehabilitation in Italy]. AB - During the year 2015 GICR-IACPR, a scientific society for Cardiovascular Prevention and Rehabilitation (CRP) in Italy, carried out several "Polls" based on its website, in order to know current attitudes of health operators involved in the management and care of cardiac patients. The Poll #1 focused on post revascularization residual myocardial ischemia, familial dyslipidemia, erectile dysfunction, sleep apnoea, and hyperuricaemia, all conditions being paradigmatic of well known situations of high cardiovascular risk and disability in the CRP setting. In the present report feasibility and results of the GICR Poll #1 are discussed. PMID- 26562989 TI - [Methanogen and human gut health--A review]. AB - Methane is produced exclusively through anaerobic fermentation of both endogenous and exogenous carbohydrates by methanogens. Methane production is detectable in about one third of healthy adult individuals. In recent years, many studies have found that methanogens played an important role in maintaining stability in the gut microbiota. Researches have paid much attention on the metabolism of the methane in the gut. The relationship between methane and intestinal dysfunction has also been investigated. The number of methanogens in irritable bowel syndrome patients is different when compared with the normal individuals. Besides, methanogens are potentially linked with obesity. This article reviewes the role of methanogens in gastrointestinal homeostasis and intestinal diseases (irritable bowel syndrome, colon cancer), as well as the relation between methanogens and obesity. PMID- 26562990 TI - [Lactobacilli and colon carcinoma--A review]. AB - Epidemiological studies showed that incidence of colon carcinoma is increased in the world. There are many difficulties to inhibit colon carcinoma because the causes of inducing colon carcinoma were various and interactive each other. Previous evidence supported the balance of the colonic microflora was critical in inhibiting colon carcinoma and the protection by colonic microflora could be improved by ingesting lactobacilli. Therefore, the biological functions and anticancer effects of lactobacilli attract attention of researchers. In this review we discussed the causes of colon carcinoma; the anticancer mechanisms of lactobacilli on the basis of our own studies. Eventually, we summarized the effects of anticancer of different components and metabolic products extracted from lactobacilli. PMID- 26562991 TI - [Advances in studies of the type III secretion system in Ralstonia solanacearum- A review]. AB - Bacterial wilt caused by Ralstonia solanacearum is one of the most devastating plant diseases worldwide. The syringe-like type III secretion system (T3SS) plays a crucial role in its pathogenicity. R. solanacearum uses the T3SS to inject effector proteins (Type III effectors) into the cytoplasm of host cells, causing diseases in susceptible plants or triggering the hypersensitive response in resistant plants. In this article we review recent advances in studies of R. solanacearum T3SS and highlight their unique features. PMID- 26562992 TI - [Diversity of faecal bacteria in several mammals by 454 high-throughput sequencing]. AB - OBJECTIVE: The aim of this study was to analyze the diversities and differences of several mammalian' s faecal bacteria, to understand the relationships between bacterium diversities and animals' evolutionary and animals' feeds. METHODS: Genomic DNA of feces was extracted and amplified for the 16S rDNA V3 tags, and then the tags were sequenced by 454 sequencing. QIIME were used to analyze faecal bacterial diversities. RESULTS: Faecal bacteria of all animals were dominated by Firmicutes, Bacteroidetes and Proteobacteria. Bacterial diversities of Hylobates hoolock, Pan troglodytes and Rhinopithecus roxellanae were the highest, followed by Panthera tigris altaica, Ailuropoda melanoleuca and Ursus thibetanus were the lowest through alpha diversity analysis. The constituents of faecal bacteria among Hylobates hoolock, Pan troglodytes and Rhinopithecus roxellanae were similar. The constituents of faecal bacteria among Ailuropoda melanoleuca, Ursus thibetanu, and Panthera tigris altaica were similar. Mainly for containning Fusobacteria, the faecal bacterial of Panthera tigris altaica differed from the other two carnivore animals through beta diversity analysis. CONCLUSION: The dominating faecal bacteria were obvious, the bacteria similarities of the two repetitions were the highest. The diversities of each animal were different and higher in the primates. Both evolution and food were related to faecal bacteria. This study provided some references for exploring the new microorganism and further research of faecal bacteria. PMID- 26562993 TI - [Genetic diversity analysis of Fusarium oxysporum f. sp. cubense populations from China using Inter-Simple Sequence Repeats-PCR (ISSR-PCR) technique]. AB - OBJECTIVE: We used Inter-Simple Sequence Repeats (ISSR) markers to reveal the genetic diversity of 95 Fusarium oxysporum f. sp. cubense ( FOC ) isolates from banana in China, for the rational control of the disease. METHODS: Eight primers were chosen for analyzing FOC isolates to study their genetic diversity by ISSR PCR. All isolates were clustered using Unweighted Pair-Group Method with Arithmetic means (UPGMA) analysis by NTSYSpc v2.10e software. RESULTS: A total of 52 sites were generated, among them 92.3% were polymorphic. Genetic distance was 0.57 to 1.00 based on the Nei's standard. Isolates were grouped into six distinct clusters (A, B, C, D, E and F) based on ISSR analysis using a genetic distance threshold of 0.68, the proportion of 51.06%, 39.58%, 5.20%, 2.08%, 1.04%, and 1.04%, respectively. CONCLUSION: There were high levels of genetic variation among the FOC isolates, and the ISSR clustering groups had obvious correlation with hosts and races of the pathogen. PMID- 26562994 TI - [Isolation and Characterization of Microbes from Pericarpium Citri Reticulatae]. AB - OBJECTIVE: The longer the Pericarpium Citri Reticulatae is preserved, the better medicinal values will be. The present work aims to isolate beneficial microbes isolated from the 7-year orange peel that might be used to produce high quality Pericarpium Citri Reticulatae. METHODS: The microbes isolated from the 7-year orange peel using 4 mediums were grouped by SDS-PAGE patterns of the whole-cell protein electrophoresis and IS-PCR DNA fingerprinting. The representative strains were further studied by physiological and biochemical tests, and phylogeny analysis. RESULTS: Total 23 bacteria were obtained from the 7-year orange peel. These strains were classified into 4 groups: the strains of group I belonged to Bacillus; the strains of group II, group III and group IV were closed to Paenibacillus. CONCLUSION: Among the representative strains of group I, II, III and IV, only the representative strain cp20 of group II has the ability of strong utilizing citrate obviously. The strain cp20 of group II were further applied to making Pericarpium Citri Reticulatae. PMID- 26562995 TI - [Engineering and heterologous expression of a nikkomycin biosynthetic gene cluster]. AB - OBJECTIVE: We expressed a nikkomycin biosynthetic gene cluster in the well characterized surrogate Streptomyces coelicolor M1146. METHODS: By using PCR targeting method, we replaced the promoters of sanG and sanF in pNIK, which contains nikkomycin biosynthetic gene cluster, with the hrdB promoter to generate pNIKm. We transferred pNIK and pNIKm into S. coelicolor M1146 by intergeneric conjugation and obtained M1146-NIK and M1146-NIKm, respectively. We then evaluated expression of the gene cluster in the heterologous host by RT-PCR. Furthermore, we also compared the antifugal activity and nikkomycin production of M1146-NIK and M1146-NIKm by bioassay against Alternaria longipes and HPLC analysis. RESULTS: M1146-NIK and M1146-NIKm exhibited antifungal activity, and they can produce a trace amount of nikkomycin X, nikkomycin Z and pseudo-Z. There was a substantial accumulation of uridine in M1146-NIK, whereas substantial accumulations of uridine, ribofuranosyl-4-formyl-4-imidazolone and pyridylhomothreonine were observed in M1146-NIKm. CONCLUSION: We successfully expressed the nikkomycin biosynthetic gene cluster in the heterologous host and identified nikkomycins and some of its key biosynthetic intermediates. This study will provide the basis for enzymatic reaction of the condensation between the two nikkomycin moieties and for the generation of hybrid antibiotics by combinatorial biosynthesis. PMID- 26562996 TI - [Adaptation of Anoxybacillus flavithermus ssp. yunnanesis E13(T) to toluene at the level of fatty acid composition of membrane]. AB - OBJECTIVE: Anoxybacillus flavithermus subsp. yunnanensis is now the only species of thermophilic bacteria able to tolerate toxic solvents at high temperature. The adaptive responses of A. flavithermus subsp. yunnanensis E13(T) to toluene on the level of fatty acid composition of membrane were studied in detail. METHODS: The extraction of fatty acids was performed according to the method described in the Sherlock Microbial Identification System manual. The fatty acid compositions were analyzed by gas chromatography mass spectrometry (GC-MS). RESULTS: In presence of 0.3% (V/V) toluene, key moment to adapt the saturated straight-chain fatty acids was that when cells grew from the lag phase to the initial growth phase in liquid. The saturated straight-chain fatty acids were continuously decreased as the strain E13(T) to grow. In survival of the cells in 100% toluene, the saturated straight-chain fatty acids increased significantly. CONCLUSION: A. flavithermus ssp. yunnanesis E13(T) alters its membrane fluidity via fatty acid composition to become more rigid when it is exposed to solvent, which is consistent that commonly found in mesophilic organic solvent-tolerant bacteria. However, it adapted its membrane by increasing straight-chain saturated fatty acids, rather than unsaturated fatty acids, which was demonstrated in mesophilic organic solvent-tolerant bacteria. PMID- 26562997 TI - [Enhanced epsilon-poly-L-lysine production by improving cellular activity during fermentation]. AB - OBJECTIVE: To assess the effect of cellular activity on epsilon-poly-1-lysine (epsilon-PL) biosynthesis and thereby to rationally improve the production, we studied the cellular activity, epsilon-PL formation and other parameters cross flask fermentation by Streptomyces ahygroscopicus. METHODS: Laser scanning confocal microscopy and a colorimetric method were used to determine cellular activity using BacLight Live/Dead and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) as viable stains. To enhance the activity of the cells in the epsilon-PL production period, yeast extract was added. RESULTS: During epsilon-PL submerged fermentation in flasks, most cells were active in the growth period (0 - 16 h); cells had metabolic activity in the growth and earlier epsilon-PL production periods between 0 and 30 h fermentation. Almost no activity was detected after 48 h fermentation when no epsilon-PL was produced. The improved fermentation achieved 2. 24 g/L epsilon-PL from 1.04 g/L. CONCLUSION: Biosynthesis of epsilon PL can be boosted by up-regulating cell activity in its production phase. PMID- 26562998 TI - [Regulation effect of CcpA protein on the biosynthesis of capsular polysaccharide in Streptococcus pneumoniae]. AB - OBJECTIVE: We studied the regulation effect of glycometabolic protein, catabolite control protein A (CcpA), on the biosynthesis of capsular polysaccharide ( CPS) in Streptococcus pneumonia. METHODS: His-tagged CcpA protein was expressed in E. coli BL21 (DE3) and purified by Ni2+ affinity chromatography. The anti-CcpA serum was obtained from immunized mice and the antibody titer was determined by ELISA. The conservation of CcpA was determined by Western blotting. In addition, binding of CcpA protein to the promoter region of cps locus was verified by EMSA. The amount of capsular polysaccharide was determined by ELISA and compared among wild type D39 strain, ccpA mutant and the complement strains. RESULTS: CcpA protein was conserved in different pneuococcal serotypes included in this study. EMSA assay revealed that CcpA protein could bind the promoter region of the cps locus in a dose-dependent manner. The absence of ccpA gene led to an increased expression of capsular polysaccharide, and complement expression of CcpA protein significantly reduced the amount of capsular polysaccharide. CONCLUSION: CcpA is conserved in Streptococcus pneumonia, which plays a role in regulation of the expression of the capsular polysaccharide. PMID- 26562999 TI - [Gene cloning, expression and characterization of N-acylhomoserine lactonase from Bacillus subtilis SS6]. AB - OBJECTIVE: This study was aimed to obtain a quorum quenching N-acylhomoserine lactonase gene from Bacillus subtilis SS6 and to characterize the enzyme. METHODS: We amplified N-acylhomoserine lactonase gene from B. subtilis SS6 by PCR methods. Gene aiiA(SS6) was cloned into the expression vector of pET28 (a) and transformed into Escherichia coli BL21. The activity of AiiA(SS6) on signal N-(3 Oxooctanoyl)-L-homoserine lactone was characterized by high performance liquid chromatography (HPLC). RESULTS: We successfully cloned an N-acylhomoserine lactonase gene from B. subtilis SS6 strain, namely aiiA(SS6) (GenBank: KP125494). The sequencing result showed that the length of aiiA(SS6) was 891 bp and the gene contained an Open Reading Frame encoding 297 amino acids. HPLC results showed that AiiA(SS6) was very active between 50 and 90 degrees C and the optimal pH was 7.6. Lineweaver-Burk treatment of the data yielded apparent K(m) and the V(max) was 0.998 mmol/L and 22.3 U/mg, respectively. Moreover, the relative activity of the enzyme remained 86% after storing at 4 degrees C for 3 months. CONCLUSION: Our findings will be helpful for further studies. PMID- 26563000 TI - [Screening for mutants with thermostabe lipase A from Burkholderia sp. ZYB002]. AB - OBJECTIVE: We improved the thermostability of LipA from Burkholderia cecapia ZYB002 by protein engineering technology to expand the application of lipase LipA. METHOD: On the basis of B-factor value of lipase LipA, series of potential mutation hotspots were selected for iterative saturation mutagenesis and the corresponding small mutation gene libraries were then constructed to screen the hyperthermal variants. RESULTS: From the above mutation libraries, we obtained a series of mutants whose enzyme half-life at 55 degrees C increased by 1.7 to 2.2 fold. CONCLUSION: B-factor iterative test (B-FIT) is feasible to mutate thermostable strains. PMID- 26563001 TI - Isolation and characterization of Pseudomonas aeruginosa strain SJTD-2 for degrading long-chain n-alkanes and crude oil. AB - OBJECTIVE: Oil pollution poses a severe threat to ecosystems, and bioremediation is considered as a safe and efficient alternative to physicochemical. METHODS: for eliminating this contaminant. In this study, a gram-negative bacteria strain SJTD-2 isolated from oil-contaminated soil was found capable of utilizing n alkanes and crude oil as sole energy sources. The efficiency of this strain in degrading these pollutants was analyzed. METHODS: Strain SJTD-2 was identified on the basis of its phenotype, its physiological features, and a comparative genetic analysis using 16S rRNA sequence. Growth of strain SJTD-2 with different carbon sources (n-alkanes of different lengths and crude oil) was assessed, and the gas chromatography-mass spectrometry method was used to analyze the degradation efficiency of strain SJTD-2 for n-alkanes and petroleum by detecting the residual n-alkane concentrations. RESULTS: Strain SJTD-2 was identified as Pseudomonas aeruginosa based on the phenotype, physiological features, and 16S rRNA sequence analysis. This strain can efficiently decompose medium-chain and long-chain n alkanes (C10-C26), and petroleum as its sole carbon sources. It preferred the long-chain n-alkanes (C18-C22), and n-docosane was considered as the best carbon source for its growth. In 48 h, 500 mg/L n-docosane could be degraded completely, and 2 g/L n-docosane was decomposed to undetectable levels within 72 h. Moreover, strain SJTD-2 could utilize about 88% of 2 g/L crude oil in 7days. Compared with other alkane-utilizing strains, strain SJTD-2 showed outstanding degradation efficiency for long-chain n-alkanes and high tolerance to petroleum at elevated concentrations. CONCLUSION: The isolation and characterization of strain SJTD-2 would help researchers study the mechanisms underlying the biodegradation of n alkanes, and this strain could be used as a potential strain for environmental governance and soil bioremediation. PMID- 26563002 TI - [Endophytic fungal diversity of four bryophyte species in Dawei Mountain, Southwest of China]. AB - OBJECTIVE: We analyzed endophytic fungi from 4 bryophyte species: Mnium sp. , Marchantia polymorpha, Polytrichum commune and Hylocomium splendens, collected from Dawei Mountain, Southwest of China, to study the diversity of fungal endophytes of bryophytes in different environment and their roles in the evolution from aquaqtic plant to terrestrial plant. METHODS: Endophytic fungi were isolated by culturable method and identified to species or genera level based on morphological characteristics and molecular analysis. RESULTS: Nine hundred fungal endophytes were isolated from 630 tissue segments of 4 different plants. All endophytes were identified to 57 taxon. Among them, Xylaria, Colletotrichum, Penicillium and Trichoderma were the dominant genera. The Shannon index (H') and similarity coefficients (CS) of endophytic fungi from 4 plants were 1.80 - 3.22 and 0.409 - 0.613, respectively, higher than those of bryophytes growing in extreme environments. CONCLUSION: The diversity and richness of endophytes from 4 bryophytes in Dawei Mountain are similar to those of plants growing in the similar environment. PMID- 26563003 TI - [Genetic diversity of peanut bradyrhizobia estimated by culture-independent vs. culture-dependent approaches]. AB - OBJECTIVE: To develop a rapid technique for estimating the percentage of bradyrhizobial nodule occupancy, we comparaed the differences of genetic diversity of peanut bradyrhizobia with culture-independent and culture-dependent methods. METHODS: We used the traditional media plate technique for isolation of peanut bradyrhizobia and directly collected the bacteroids from peanut nodules. The BOX-PCR fingerprintings were compared after amplification with the DNAs of peanut bradyrhizobial isolates by culture-dependent approach and bacteroids by culture-independent approach. RESULTS: The percentage of testing for peanut bacteroids was 81.8% with culture-independent method, and 85 genotypes of BOX-PCR were obtained. The percentage of isolation for peanut bradyrhizobia strains was 72.7% and 71 genotypes of BOX-PCR were produced. There were totally 17 corresponding BOX-PCR genotypes obtained by both methods. CONCLUSION: The culture independent method for direct analysis of genetic diversity from bacteroids in nodules can much more rapidly and clearly find the dominant genetic groups in different soil samples and fast figure out the.percent of the rhizobia nodule occupancy. PMID- 26563004 TI - [Identification of a point mutation in the promoter region of cps operon responsible for capsular polysaccharide deficiency in Streptococcus pneumniae SPY1]. AB - OBJECTIVE: To determine if the point mutation of nt313713 T --> C in the promoter region of capsular polysaccharide biosynthesis (cps) operon is responsible for the deficiency of capsular polysaccharide in S. pneumoniae SPY1 strain. METHODS: Western blot was used to compare the amounts of capsular polysaccharide between the wild-type strain and SPY1 strain. Real-time quantitative PCR was used to determine transcription levels of the first four genes of cps operon , cps2A, cps2B, cps2C and cps2D. The lacZ gene was used as a reporter gene to report the strength of the promoters on cps transcription. The cps promoter was amplified by PCR from the wild-type strain or SPY1 strain. The amplified fragments were cloned into shuttle vector pEVP3, transformed into S. pneumoniae D39 or SPY1 strain. The transcription activities of the promoters on capsular polysaccharide biosynthesis were determined by using beta-galactosidase as the reporter. Transmission electron microscopy and the Neufeld test were used to reveal the changes in capsule. RESULTS: Compared to that in the wild-type strain, mRNA levels of the cps genes were significantly decreased in SPY1 strain. The amount of CPS was also decreased in SPY1 strain. beta-galactosidase activities in SPY1-pEVP3-cps promoter(SPY1) and D39-pEVP3-cps promoter(SPY1) were decreased by about 79% and 76%, respectively, compared to that of the control. Transmission electron microscopy showed that the amount of the capsular polysaccharide of SPY1-pEVP3 cps promoter(D39) strain was restored to the wild-type level. In addition, capsular polysaccharide was absent in the D39-pEVP3-cps promoter(SPY1) (NC_008533. 1 313713 T --> C) strain as determined by Neufeld test. CONCLUSION: The point mutation of nt313713 T --> C in the cps promoter region results in a significantly reduced transcription of the cps genes, which is responsible for the significant reduction or even absence of the biosynthesis of capsular polysaccharide in SPY1 strain. PMID- 26563005 TI - [Effect of phosphorus supply and signal inhibitors on oxalate efflux in ectomycorrhizal fungi]. AB - OBJECTIVE: Phosphorous (P) is one of the essential elements for tree growth in forests. It is beneficial to characterize oxalate secretion by ectomycorrhizal fungi in response to P supply for understanding the mechanism of P mobilization in soils. METHOD: In the present experiment, the influence of P supplies and inhibitors of Ca2+ signal/anion channel on oxalate efflux in ectomycorrhizal fungi was studied in the pure liquid culture with various P concentrations. RESULTS: Ectomycorrhizal fungi released a large amount of H+ and organic acids such as oxalate, acetate, malate, citrate and succinate, which are important for mobilization of insoluble P in the soils. Oxalate accounted for 15. 14% to 36. 01% of the total organic acids released by the fungi and was accelerated in culture solution under the condition of low P supply, but inhibited under normal and high P. CONCLUSION: Ectomycorrhizal fungi released a large amount of H+ and organic acids, particularly oxalate, which might be beneficial to inorganic P mobilization in the soils and improvement of P nutrition for their host plants. PMID- 26563006 TI - HPV-positive head and neck tumours, a distinct clinical entity. AB - A worldwide rise in the incidence of oropharyngeal squamous cell cancer has been recorded over the past decade. This rise has been attributed to an increase in oncogenic human papilloma virus (HPV) infections. The biology of HPV-positive oropharyngeal cancer is distinct; it includes p53 degradation, retinoblastoma pathway inactivation, and p16 upregulation. The best method for detecting HPV in tumour material is controversial; both in-situ hybridisation and PCR are commonly used. However, p16 can serve as a potential surrogate marker, and therefore, p16 immunohistochemistry is widely used in clinical practice. Compared to HPV negative cancers, HPV-positive oropharyngeal cancer appears to be more responsive to chemotherapy and radiotherapy. Thus, p16 can serve as a prognostic marker for enhanced overall survival and disease-free survival. In this review, we aimed to highlight the current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma. PMID- 26563007 TI - Cervical lymph node metastases and T1 squamous cell carcinoma of the lips. AB - OBJECTIVE: The occurrence of cervical lymph node metastasis is a major prognostic factor for head and neck squamous cell carcinoma (SCC) of the lip. This study focuses on patients with T1 stage tumours,in order to describe the prevalence of metastatic lymphadenopathies. METHODS: A multicenter retrospective study was performed in three tertiary care referral centers and included 59 patients surgically treated for T1 stage SCC of the lips from January 1996 to December 2006. This surgical treatment concerned the tumour, with cervical neck dissection when lymph node metastasis was suspected. RESULTS: Cervical lymph node metastasis was found and histologically proven in 7 patients (11.9% of the cases, pN+ group; 95% confidence interval, 3.6 to 20.2%) during follow-up, never at the time of diagnosis. Metastasis appeared 13.3 +/- 7.9 months (min. 5.3 months, max. 29.1 months) after the initial treatment and involved the IB level in all cases. Tumour progression was significantly longer in the pN+ group compared to patients with no lymph node metastases (sN-group). The pN+ group also had a significantly higher proportion of poorly or moderately differentiated tumours, and a significant decrease in overall survival, disease-free survival, and disease specific survival. CONCLUSION: Lymph node metastasis occurs in roughly 12% of T1 stage SCC of the lips, and the management of neck lymph node areas is necessary. A randomized trial is needed to determine the proportion of occult lymph node metastases in T1N0 patients and the impact of this therapeutic procedure on survival. PMID- 26563009 TI - Bipolar Quantum Molecular Resonance versus Blunt Dissection tonsillectomy. AB - OBJECTIVES: This study compared a quantum molecular resonance tonsillectomy (QMRT) to a standard blunt dissection tonsillectomy (BDT) for effectiveness and safety. METHODOLOGY: From January 2011 to September 2012, we recruited 80 children (ages 3 to 16 y) with paediatric obstructive sleep apnoea syndrome and/or recurrent tonsillitis. Patients were randomly assigned to receive QMRT (N = 40) or BDT (N = 40). The operating time and blood loss during surgery were evaluated. During the first postoperative week, the patients' parents completed a questionnaire to evaluate bleeding, ear and neck pain, nausea, vomiting, interrupted sleep, oral liquid intake or discomfort in fluid assumption, and analgesic consumption. RESULTS: The average tonsillectomy duration was significantly shorter in the QMRT group (22.07 min +/- 9.05) than in the BDT group (35.12 min +/- 13.32; p < 0.000005). The average blood loss during tonsillectomy was significantly lower for the QMRT group (5.62 ml +/- 7.44) than for the BDT group (43 ml +/- 33.20; p < 000000001). However, the BDT group reported significantly lower pain scores than the QMRT group on days 2 (p < 0.05), 5 (p < 0.05), and 6 (p < 0.05); on other days, the groups were not significantly different. The BDT group reported two early and one late bleeding episodes; the QMRT group recorded only two late bleeding episodes. CONCLUSIONS: QMRT significantly reduced the operating time and intra-operative blood loss. No significant differences were found between the two techniques in postoperative pain or bleeding. PMID- 26563008 TI - Pharyngocutaneous fistulae after total laryngectomy: analysis of the risk factors and treatment approaches. AB - OBJECTIVES: To investigate the incidence and predisposing factors in the development of postoperative pharyngocutaneous fistula (PCF) after total laryngectomy. METHODOLOGY: A total of 166 patients with complete medical records who underwent total laryngectomy (TL) due to laryngeal cancer were analysed retrospectively. The mean age of the patients was 57.4 (+ 19.6) years. This study looked at a total of 32 different parameters considered to be effective in the development of pharyngocutaneous fistula after total laryngectomy. RESULTS: Thirty-two patients (19.2%) had a pharyngocutaneous fistula. Aged over 61 years (p = 0.003), Diabetes Mellitus (DM) (p = 0.002), alcohol use (p = 0.006), history of preoperative radiotherapy (p = 0.001), preoperative tracheotomy (p = 0.017), postoperative low levels of haemoglobin (Hb) (p = 0.029), low levels of preoperative albumin (p = 0.001), total protein and a low alb/glb (albumin/globulin) ratio (p = 0.001), serum prealbumin levels on the third and seventh postoperative days (p = 0.001), high postoperative CRP levels (p = 0.002), T4 stage (extralaryngeal) and presence of transglottic lesion (p = 0.003), presence of stage IV (p = 0.012) lesion, primary surgery accompanied by bilateral neck dissection (p = 0.047), T-shaped oesophagus suture, postoperative bleeding (p = 0.07), presence of postoperative fever (p = 0.001), presence of skin defect in the anterior neck (p = 0.001) and presence of postoperative depression (p = 0.001) were found to be statistically significant factors in the development of PCF. CONCLUSIONS: Our study found many parameters associated with an increased risk of the development of PCF. According to the multivariate regression analysis, aged over 61 years, DM, preoperative RT, preoperative tracheostomy, postoperative Hb under 10 g/dl, prealbumin under 17 mg/dl on the third postoperative day, and a postoperative fever of 38.3 degrees C and above were found be associated with a higher risk of the development of fistulae more than the other risk factors. PMID- 26563010 TI - Which technique is better for cholesteatoma surgery? AB - OBJECTIVE: The objective of this study was to evaluate the long-term surgical outcomes and recurrence rates of three surgical techniques that are commonly used for cholesteatoma. PATIENTS AND METHODS: The hospital records of 132 patients with primary cholesteatoma who underwent surgery between January 1996 and December 2006 were evaluated retrospectively. Twelve cases had bilateral disease, and a total of 144 ears were treated. The patients were divided into three groups according to surgical technique: modified radical mastoidectomy (MRM) (n = 48 ears), radical mastoidectomy (RM) (n = 42 ears), and intact canal wall mastoidectomy (ICWM) (n = 54 ears). MRM and RM procedures are canal wall down (CWD) techniques, whereas the ICWM procedure is a canal wall up (CWU) technique. Postoperatively, all patients were followed up yearly for at least 6 years. The otomicroscopic features, cholesteatoma extension, surgical findings, and recurrence rates were compared in the groups. RESULTS: Preoperative otomicroscopic examination showed attic retraction or perforation in 32% of the cases and central perforation in 11%. There was a higher cholesteatoma recurrence rate in the ICWM group than in the MRM and RM groups (p < 0.05), but there was also better hearing gain in the ICWM group (p < 0.05). CONCLUSION: There are several surgical techniques for eradicating cholesteatoma. Our study found that CWD procedures (RM, MRM) were more effective for the eradication of cholesteatoma, but hearing gain was better when a CWU technique was used. The choice of surgical technique should be individually tailored based on the pre operative imaging and hearing examination findings. PMID- 26563011 TI - Efficacy of medical therapy in the prevention of residual dizziness after successful repositioning maneuvers for Benign Paroxysmal Positional Vertigo (BPPV). AB - OBJECTIVES: The aim of this study was to investigate the efficacy of trimetazidine, betahistine, and ginkgo biloba extract in the treatment of residual dizziness after successful repositioning maneuvers for benign paroxysmal positional vertigo. METHODOLOGY: This was a randomized controlled clinical trial. Complete clinical data were analyzed from 100 patients (27 men and 73 women; mean age 52.16 +/- 13.2 years, range 11-80 years) with BPPV who underwent succcessful repositioning maneuvers and then received betahistine, trimetazidine, gingko biloba extract, or no medication (n = 25 for each group) for 1 week. On days 1, 3, and 5 after the repositioning maneuver, scores obtained from the Dizziness Handicap Inventory (DHI) questionnaire were compared. RESULTS: There were no statistically significant differences in the premedication DHI scores of patients with residual dizziness among the four groups (p > 0.005). After 3 and 5 days of treatment, the mean DHI scores of the groups receiving medication did not differ significantly from the the mean DHI score of the control group (p > 0.005). CONCLUSIONS: Our study results suggest that betahistine, trimetazidine, and gingko biloba extract do not alleviate residual dizziness after successful repositioning maneuvers. PMID- 26563012 TI - Oral steroids and intraoperative bleeding during endoscopic sinus surgery. AB - OBJECTIVES: Our main objective was to investigate the effect of preoperative oral steroids on intraoperative bleeding and quality of the surgical field during endoscopic sinus surgery (ESS). Our second objective was to determine whether the osteitis score could be used to predict the volume of intraoperative bleeding. METHODOLOGY: This double-blinded, randomized trial included 65 patients with chronic rhinosinusitis with nasal polyps. The corticosteroid group received oral prednisolone (1 mg/kg), administered to patients once daily for 2 days and then tapered down, with treatment completed on the day 10. The control group received placebo before the operation. Endoscopic exams were recorded, and preoperative sinus computed tomography scans were scored. Intraoperative blood loss was recorded. Quality of the surgical field was assessed by the surgeon, using a linear scale from 1 to 10. RESULTS: The mean bleeding volume was 239 ml in the corticosteroid group and 203 ml in control group. There was no significant difference between the groups (p = 0.495). Surgical field quality scores were higher in the corticosteroid group than in the control group, but the difference was not significant (p = 0.36). There was no statistically significant relationship between the bleeding volume and Kennedy Osteitis Scores in corticosteroid group (r = 0.225, p = 0.186) and control group (r = 0.084, p = 0.663). CONCLUSION: Our findings suggest that using oral corticosteroids, which have rare but serious side effects, is not necessary in the preoperative period. Furthermore, we found that the radiological osteitis score was not a suitable marker for predicting intraoperative bleeding volumes. PMID- 26563013 TI - Changes in nasal flora one year after endoscopic dacryocystorhinostomy. AB - PURPOSE: This study investigated changes in patient nasal and conjunctival flora one year after endoscopic dacryocystorhinostomy (EDSR). METHODS: The prospective study included 20 patients that underwent EDSR due to chronic dacryocystitis. Conjunctival and nasal cultures were obtained one year after EDSR from both study and control groups. Patient characteristics, chronic illnesses, the severity and duration of complaints, culture results, and the stent removal time were recorded and analyzed. RESULTS: In the study group, the most commonly isolated microorganism in the nasal cultures was coagulase-negative staphylococcus (n = 11), and the second most commonly isolated microorganism was Staphylococcus aureus (n = 7). A total of 11 (55%) of the nasal cultures in the study group showed the presence of multi-drug resistant (MDR) bacteria, as did 2 (10%) of the nasal cultures in the control group (p = 0.007). CONCLUSIONS: One year after EDSR surgery with silicon stent placement, we detected changes in the nasal flora in the operated side compared with the non-operated side. Even though more than half of the nasal cultures in the study group were positive for MDR bacteria, these microorganisms did not cause attacks of dacryocystitis or affect surgical success. PMID- 26563014 TI - Chronic rhinosinusitis; histopathologic study of osteitis in surgery cases. AB - OBJECTIVE: To determine whether osteitis is associated with primary and revision surgery in patients with chronic rhinosinusitis (CRS) and to determine its relationship with mucosal inflammation. METHODOLOGY: Patients were divided into two groups based on a history of prior endoscopic sinus surgery (ESS). The primary surgery group included 74 patients who had ESS for the first time, and the revision surgery included 37 patients who had repeat ESS. Histopathological examinations were performed on specimens taken from the bony septa of the ethmoid with the overlying mucosa. RESULTS: The incidence of osteitis was 70.3% in patients in the revision surgery group and 56.8% in patients in the primary surgery group (p = 0.229). Osteitis was associated with tissue eosinophilia and a predominance of inflammatory cells (p = 0.01 and p = 0.01, respectively). CONCLUSIONS: Surgery may not be the primary cause of bone remodeling in the sinus area. Mucosal inflammation had no effect on the incidence of osteitis when it was associated with tissue eosinophilia in CRS. Patients with osteitis may benefit most from postoperative corticosteroid therapy to prevent further recurrence. PMID- 26563015 TI - Schwannoma of the nasal septum presenting as a multicentric neuronal tumour. AB - PROBLEM: Schwannomas (neurilemmomas) are benign primary tumours that arise from Schwann cells. Schwannomas arising from the nasal septum are exceptionally rare. Here, we report a unique case of schwannoma of the nasal septum presenting as a multicentric neuronal tumour. RESULTS: A 40-year old male sustained intermittent left tinnitus. Magnetic resonance imaging revealed masses near the nasal septum and upper cervical cord in addition to a tumour in the left cerebellopontine (CP) angle. The tumour in the nasal septum was completely resected by endoscopic endonasal surgery and diagnosed as a typical schwannoma. The CP angle tumour was treated with stereotactic radiosurgery, while the asymptomatic cord lesion showed no significant growth and remains under observation. CONCLUSION: Endoscopic endonasal surgery is useful for the resection of schwannomas of the nasal septum. Schwannomas of the nasal septum may present as multiple neuronal tumours. PMID- 26563016 TI - Inflammatory pseudotumour of the maxillary sinus mimicking malignancy. AB - Inflammatory pseudotumours of the paranasal sinuses are rare entities and can be easily confused with aggressive malignant tumours. In this report we describe the characteristic behavior of inflammatory pseudotumours in the maxillary sinus. We present a case of a 47-year-old Caucasian woman, who presented in our ENT department because of progressive nasal obstruction, epistaxis, and epiphora. The clinical as well as the radiological findings suggested a maxillary sinus neoplasm, most probably of malignant nature. The histopathological examination showed an inflammatory pseudotumour of the maxillary sinus with polypoid structure and no signs of malignancy. PMID- 26563017 TI - Vocal fold hyalinosis in Urbach-Wiethe disease, a rare cause of hoarseness. AB - BACKGROUND: Lipoid proteinosis is an autosomal recessive disorder characterized by hyalin deposits in the skin and mucosa of the upper aerodigestive tract; currently, no treatment exists. Nearly all patients experience hoarseness and speech difficulties, due to hyalin deposition in the vocal folds and diminished mobility in infiltrated lips, tongue, and palate. METHODS: We describe a patient with extensive hyalin plaques on the vocal folds, which resulted in near-aphonic hoarseness. Hyalin deposits in the vocal folds and skin were treated with laser resection. RESULTS: Both the vocal folds and skin improved in appearance, with smoother surface epithelium. However, the patient's speech remained impaired, due to extensive hyalin plaques in the mouth, tongue, and lips. The voice improved only temporarily. CONCLUSIONS: Laser resection of hyalin plaques in the vocal folds and skin is a feasible treatment for lipoid proteinosis. However, speech may remain severely limited, due to impaired tongue and lip movement. PMID- 26563018 TI - Superficial circumflex iliac artery perforator flap for reconstruction of oral defects after tumor resection. AB - BACKGROUND: The superficial circumflex iliac artery perforator (SCIP) flap, which is the most recent advance in free flap surgery, is described as an evolution of the conventional free groin flap. It has been applied to limb and penile reconstruction. The SCIP flap is versatile and has many advantages, but there are few reports on the application of the SCIP flap to head and neck defects. CASE REPORT: We used a SCIP flap for reconstruction after resection of an oral malignant tumor in two women, aged 43 and 55 years, who presented between 2010 and 2012 with squamous cell carcinoma of the right floor of the mouth and tongue. After resection, the SCIP flap was elevated and used to reconstruct the defect Both flaps survived well. CONCLUSIONS: We confirmed that the SCIP flap is an ideal thin, pliable, and reliable skin flap for reconstructing intra-oral soft tissue defects with minimal donor-site morbidity. PMID- 26563019 TI - What's the plan for continuing care? PMID- 26563020 TI - When things don't go well, what can we learn? Learning from our mistakes to provide the best quality care for our clients. PMID- 26563021 TI - Strategies to reduce wound dressing waste. AB - Inappropriate use of dressing supplies and the amount of unused, unopened dressings, often stockpiled in patient rooms and discarded upon patient discharge begs the question about the environmental impact of this common practice. Thousands of dollars could be saved each year if nurses placed more emphasis on prevention and education, and addressed wound care in a standardized way that blends cost-effectiveness with evidence-based practice. PMID- 26563022 TI - Coming of age. ATTITUDES TOWARD ADULT POPULATION PRESENT BARRIERS AND OPPORTUNITIES TO IMPROVE CARE. PMID- 26563023 TI - It's time to have 'the talk'. RISING STI RATES AMONG OLDER ADULTS A COMPLICATED ISSUE. PMID- 26563024 TI - COMING FULL CIRCLE. Nurse and patient reunite after 20 years, and what they learn is unbelievable. PMID- 26563025 TI - Medical missions abroad: shorter commitment times made it possible for RN Kelly Arraf. PMID- 26563026 TI - RN Leanne Foff makes a difference both at home and abroad. PMID- 26563027 TI - Nurses embody concept of patient-centred care at South Health Campus. PMID- 26563028 TI - Chronic disease management a clear call to action. PMID- 26563029 TI - Quantitative and qualitative morphologic, cytochemical and ultrastructural characteristics of blood cells in the Crested Serpent eagle and Shikra. AB - The Crested Serpent eagle (Spilornis cheela) is a bird of prey found in the tropical rain forest in Thailand. The Shikra (Accipiter badius) is a sparrow hawk and common resident in Thailand. Blood samples from 9 Crested Serpent eagles and 12 Shikras were obtained from September 2010 to November 2014. They were clinically healthy and negative for blood parasites detectable by light microscopy and molecular techniques (partial cytochrome b gene for avian malaria and partial 18S rRNA gene for trypanosome). Cytochemical staining (Sudan black B, peroxidase, alpha-naphthyl acetate esterase, and beta-glucuronidase) and transmission electron microscopy were performed. Hematological results were reported as the mean +/- standard deviation and median. Heterophils were the most prevalent leukocytes in the Crested Serpent eagle, but in the Shikra, lymphocytes were the most prevalent leukocytes. In the Shikra, some vacuoles were observed in the cytoplasm of the eosinophils. All blood cells in both types of raptors stained positively for beta-glucuronidase but negatively for peroxidase. The ultrastructure of heterophils showed more clearly differentiate long rod granules in Crested Serpent eagle and spindle-shaped granules in Shikra. The ultrastructure of the eosinophils in the Crested Serpent eagle revealed varied electron-dense, round-shaped granules with round, different electron-dense areas in the centers of some granules, which differed from the structure reported for other raptors. These quantitative results may be useful for clinical evaluations of Crested Serpent eagles and Shikras that are undergoing rehabilitation for release. PMID- 26563030 TI - Nfkbiz regulates the proliferation and differentiation of keratinocytes. AB - Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappaB) inhibitor zeta (Nfkbiz) is a nuclear inhibitor of NF-kappaB (IkappaB) protein that is also termed as molecule possessing ankyrin repeats induced by lipopolysaccharide, interleukin-1-inducible nuclear ankyrin repeat protein, or IkappaBzeta. We found previously that disrupting the Nfkbiz gene resulted in atopic dermatitis-like lesions in mice, suggesting an important role for Nfkbiz in the skin. In this study, we examined the cellular function of Nfkbiz in keratinocytes. Immunohistochemical analyses for Ki-67 revealed that Nfkbiz-/- keratinocytes were hypoproliferative. In skin from Nfkbiz-/- mice, the expression of the keratinocyte differentiation markers K10 and filaggrin were reduced, although that of K14 was unchanged. The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assay revealed that the frequency of apoptosis was comparable between control and Nfkbiz-/- keratinocytes. Interestingly, the subcellular localization of the NF-kappaB subunits and the transcriptional activity of NF-kappaB were not changed in Nfkbiz-/- keratinocytes. These findings indicate a novel possible role of Nfkbiz in controlling the proliferation and differentiation of epidermal keratinocytes through NF-kappaB-independent mechanisms. PMID- 26563031 TI - Long-term p-nitrophenol exposure can disturb liver metabolic cytochrome P450 genes together with aryl hydrocarbon receptor in Japanese quail. AB - P-Nitrophenol is a major metabolite of some organophosphorus compounds. It is considered to be one of nitrophenol derivatives of diesel exhaust particles that induce substantial hazards impacts on human and animal health. P-Nitrophenol (PNP) is a persistent organic pollutant. Consequently, bioaccumulation of PNP potentiates toxicity. The objectives of the current study were to assess the potential hepatic toxicity and pathway associated with long-term exposure to PNP. Japanese quails were orally administered different doses of PNP for 75 days. Liver and plasma samples were collected at days 45 (45D), days 60 (60D) and days 75 (75D). Liver histological changes and plasma corticosterone levels were assessed. Basal mRNA level of cytochromes P450 (CYP 450) (CYP1A4, 1A5, 1B1), heme oxygenase (HO-1), and aryl hydrocarbon receptor 1 (AhR1), from the liver of exposed birds and primary hepatocytes cultured for 24 hr with PNP, were analyzed using quantitative real-time PCR. The results revealed various histopathological changes in the liver, such as lymphocytes aggregation and hepatocytes degeneration. Significant increases in corticosterone levels were reported. After 60-days of in vivo exposure, the birds exhibited an overexpression in the liver CYP1A4, 1B1, AhR1, and HO-1. Furthermore, with continuous PNP administration, an overall downregulation of the tested genes was observed. In vitro, although a significant overexpression of CYP1A4, 1B1, and HO-1 was observed, CYP1A5 was downregulated. In conclusion, PNP can interfere with the liver CYP 450 enzymes and modulate HO-1 expression in the in vitro and in vivo experiments. Hence, it could have serious deleterious effects on humans, livestock, and wild animals. PMID- 26563032 TI - Diagnostic application of recombinant equine merozoite surface antigen-1 in elisa for detection of Theileria equi specific antibodies. AB - Theileria equi merozoite surface antigens have been an important candidate for development of diagnostics. We developed ELISA based on EMA-1 recombinant antigen, so as to widen our diagnostic confidence in detection of antibodies against T. equi in sero-surveillance studies. The 547 bp EMA-1 gene fragment encoding high hydrophilic antigenic region was expressed with glutathione-S transferase tag in prokaryotic system and purified protein (43 kDa) was used for development of ELISA (EMA-1t/ELISA). The EMA-1t/ELISA clearly differentiated T. equi-infected from Babesia caballi-infected horse sera or normal horse sera. The results of the study were validated with previously developed (EMA-2)ELISA on serum samples of known T. equi infection status and a very high correlation (0.93) was recorded between the relative percent positivity (RPP) values. Further diagnostic sensitivity of EMA-1t/ELISA was 0.92 while specificity was 1.0, indicating its suitability for sero-epidemiological studies. This assay was applied on serum samples (n = 240) collected from field horses in northern part of India. High sero-prevalence of T. equi antibodies were diagnosed in serum samples collected from Haryana state (74%) and Uttarakhand state (36.31%). Results of this study suggested that the 43 kDa EMA-1 expressed protein could be a reliable immunodiagnostic antigen in ELISA for T. equi sero-prevalence studies. PMID- 26563033 TI - Systemic and local bactericidal potentiality in late lactation Holstein-Friesian cows following a combined antibiotics and Enterococcus faecium SF68 dry-cow treatment. AB - Antibiotic dry-cow treatment contributes a major part to the total use of antibiotics in dairy herds. Enterococcus faecium strain SF68 (SF68) was of human origin but has been authorized in EU as probiotic feed additive. In the present study, one of the front and rear quarters of twelve late lactation Holstein Friesian cows were infused once with a commercial antibiotic dry-cow formula (antibiotics quarter) on the first milk-stasis day (d 1), when the contrallateral quarters were infused with 5 x 10(8)-CFU SF68 plus half-dose antibiotic dry-cow formula (SF68/antibiotics quarter) meanwhile. Gelatinase level and cellular reactive oxygen species (ROS) production capacity were measured for blood and quarter secretion. The results showed that the count of blood total leukocytes minorly decreased on d 3 only but the microscopic somatic cell count (MSCC) continuously increased up to d 7, especially in SF68/antibiotics quarters. Plasma level of gelatinase A remained similar up to d 7 but gelatinase B was not detectable in plasma throughout the study. The level of gelatinase A in quarter secretion increased up to d 7 but gelatinase B increased even more drastically, especially in SF68/antibiotics quarters. The ROS production capacity of blood leukocytes increased temporarily only on d 3, but that of milk cells continuously increased up to d 7, especially in SF68/antitiotics quarters. Overall, late lactation Holstein-Friesian cows were systemically adaptable to the combined antibiotics and SF68 dry-cow treatment, while the local bactericidal potentiality in mammary gland was actively responsive to additional SF68 intramammary treatment. PMID- 26563035 TI - Preparing for the boomer effect. Less experienced nurses may step into nurse manager role sooner. PMID- 26563034 TI - Molecular characterization of Mycobacterium orygis isolates from wild animals of Nepal. AB - Mycobacterium orygis, a new member of the Mycobacterium tuberculosis complex, was isolated from a captive spotted deer (Axis axis) and a blue bull (Boselaphus tragocamelus) in Nepal. Analyses by spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing, region of difference and single nucleotide polymorphism of genes gyrB, mmpL6, TbD1, PPE55 and Rv2042c confirmed the isolates as M. orygis. Moreover, analyses by spoligotyping (SIT587) as well as MIRU-VNTR showed that the isolates shared a similar pattern with many reported isolates. From previous and the present studies, it can be inferred that South Asia is one of the endemic regions for M. orygis. Further investigation including a larger sample size and different host interaction will help to understand the ecology and epidemiology of M. orygis in Nepal. PMID- 26563036 TI - Collaboration is key. Nurse experts discuss challenges, pose solutions. PMID- 26563037 TI - Zero tolerance. ANA releases new position statement on workplace violence, bullying. PMID- 26563038 TI - Nurses at the table: in the United States and around the world. PMID- 26563040 TI - Academy calls for collective action to include social and behavioral determinants of health in EHR. PMID- 26563039 TI - Calling all new RNs! Introducing exclusive ANA member benefits. PMID- 26563041 TI - Urgent change needed to improve diagnosis in health care. PMID- 26563042 TI - What nurses are saying.... PMID- 26563043 TI - Emergency nurses and end-of-life care. PMID- 26563044 TI - Protecting nursing home residents with proper antibiotic use. PMID- 26563045 TI - New anthrax vaccine underway with HHS support. PMID- 26563047 TI - Federal Health IT Strategic Plan 2015-2020 released. PMID- 26563046 TI - Follow up: Who is watching whom? ONA offers social media guidelines to protect nurses, others. PMID- 26563048 TI - Lessons learned from the 2014 Ebola epidemic. PMID- 26563049 TI - Ebola revisited: ANA, CDC address ongoing efforts. PMID- 26563050 TI - ANA recommends RNs be immunized against vaccine-preventable diseases. PMID- 26563051 TI - White House report on occupational licensing. PMID- 26563052 TI - Barbara Thoman Curtis: The quintessential nurse activist and change agent. PMID- 26563053 TI - Members take action to reduce effects of climate change. PMID- 26563054 TI - Foundation's Corporate Advisory Board adds strength to mission. PMID- 26563055 TI - Examining compassion fatigue, compassion satisfaction. PMID- 26563056 TI - Celebrating mandatory OT decision, safer patient care. PMID- 26563057 TI - The making of a presidential endorsement. PMID- 26563058 TI - New topic focuses on trends, challenges in care coordination. PMID- 26563059 TI - Prolong Restoration of the Water Quality of River Ganga Effect of Heavy Metals and Radioactive Elements. AB - The genesis of the present research was the belief since ages and the observations made through some studies that the water of river Ganga has unique characteristics, which allows storage of water quality even on prolong storage. Very few systematic studies have been conducted to support the contention that the Ganga water indeed has some special composition that could be attributed to its unique storage capacity. It was postulated that prolong restoration of water quality depends on the ability to arrest microbial activity that is generally responsible for deterioration in water quality on prolong storage. Hence, attempt has been made to identify the parameters that are likely to influence the prolong storage of river water. Along with Ganga river water, other three major rivers, viz. Yamuna, Godavari and Narmada, were selected for comparison. Emphasis was made on estimation of heavy metals, radioactive elements, dissolved carbon and other physicochemical parameters such as temperature, pH, alkalinity, hardness and dissolved organic carbon. Based on the available information regarding the impact of heavy metals, radioactive elements vis-a-vis the chemical composition of water on microorganisms in the aquatic environment, an overall impact score for the waters of the four Indian rivers selected in the study has been assigned. PMID- 26563060 TI - Occurrence of Perchlorate in Various Water Sources in South India. AB - Iodine is necessary for synthesis of thyroxine within the thyroid gland. Iodine deficiency leads to hypothyroidism and goitre. Sometimes, even when sufficient iodine is present in food and water, goitre occurs. This could be due to some other competing ions in the ingested food and water, which prevent incorporation of iodine into the thyroid gland. Perchlorate is one such ion and has thirty times more affinity to thyroid, than iodine. Perchlorate is discharged into the environment by fireworks and explosives industries. Hence, the perchlorate levels would be higher in and around such industries. This study was done to determine the perchlorate exposure to humans in their habitat. In this study, perchlorate levels in different water sources in localities with and without such industries were ascertained. The estimation was done by two methods (i) Thionine ion pair spectrophotometry and (ii) ion exchange chromatography with conductivity detection methods. In the results, perchlorate level was significantly high in different water sources of industrialized areas, when compared to non-industrial areas. These high levels could be the explanation for the high prevalence of goitre in areas with sufficient iodine availability. PMID- 26563061 TI - Groundwater Geochemistry in the Southeastern Part of Anantapur District, Andhra Pradesh, with Special Reference to Fluoride Distribution and Its Impact on Health. AB - Groundwater is the major water-source for drinking and irrigation in drought prone southeastern part of Anantapur District, Andhra Pradesh (India). Geochemically, the groundwater is characterized by alkaline nature, higher contents of Na+ over K+, Ca2+ over Mg2+ and Cl- over NO3- more or less equal amounts of HCO3- and SO4(2-), and fluoride 0.5 to 5.51 mg/L, that is ~2-5 times over the W.H.O. (2004) prescribed limit of 1.5 mg/L for drinking. Due to high F in water, this region is severely affected by endemic fluorosis. High fluoride content in groundwater is attributed to release of F- into water from F-bearing rocks in this tropical region during their weathering and partial evaporation of such water. Use of this groundwater with high F- for drinking and irrigation for dry crops led to many health problems, viz. dental and skeletal-fluorosis, and deformation of bones, manifested in both children and adults. This calls for effective regional-scale defluoridation of water in this part to bring to permissible limit prior to its use, besides adoption of methods like rainwater harvesting. PMID- 26563062 TI - Assessment of Pesticide Contamination in Ground Water from Intensive Agricultural Sites, Using Gas Chromatography-Mass Spectrometry. AB - A methodology proposed by US EPA (8081-B) is adopted with some modifications for low level pesticide residue analysis in ground water samples. The method is based on liquid-liquid extraction and gas chromatography with electron capture detector (GC-ECD), and confirmed by gas chromatography-mass spectrometry (GC-MS). For this study, different classes of pesticides were selected, both recent and old persistent molecules, namely organochlorine and pyrethroid insecticides. Pesticide residues could be detected in the low- to sub-ppb range (0.5 ppb and below) with good precision (0.071-0.12%, average 0.06-0.71% R.S.D.) and extraction efficiency (78-93%) for the majority of analytes. This methodology has been applied in a monitoring program of water samples from an intensive agricultural area in five districts of Maharashtra (India). The pesticides detected in the two-year sampling program (2008/2009) were Alpha HCH, Beta HCH, lindane, Delta HCH, p,p'-DDE, o'p-DDD, Alpha Endosulphan, Beta Endosulphan and endosulfan sulphate. A survey of the type of pesticides being used in the area, along with the crop pattern, has also been done. The outcome of the study would be useful in predicting the pathway of pesticides from agricultural field to consumer end, and persistence of pesticides in the water bodies. PMID- 26563063 TI - Locations of Sampling Stations for Water Quality Monitoring in Water Distribution Networks. AB - Water quality is required to be monitored in the water distribution networks (WDNs) at salient locations to assure the safe quality of water supplied to the consumers. Such monitoring stations (MSs) provide warning against any accidental contaminations. Various objectives like demand coverage, time for detection, volume of water contaminated before detection, extent of contamination, expected population affected prior to detection, detection likelihood and others, have been independently or jointly considered in determining optimal number and location of MSs in WDNs. "Demand coverage" defined as the percentage of network demand monitored by a particular monitoring station is a simple measure to locate MSs. Several methods based on formulation of coverage matrix using pre-specified coverage criteria and optimization have been suggested. Coverage criteria is defined as some minimum percentage of total flow received at the monitoring stations that passed through any upstream node included then as covered node of the monitoring station. Number of monitoring stations increases with the increase in the value of coverage criteria. Thus, the design of monitoring station becomes subjective. A simple methodology is proposed herein which priority wise iteratively selects MSs to achieve targeted demand coverage. The proposed methodology provided the same number and location of MSs for illustrative network as an optimization method did. Further, the proposed method is simple and avoids subjectivity that could arise from the consideration of coverage criteria. The application of methodology is also shown on a WDN of Dharampeth zone (Nagpur city WDN in Maharashtra, India) having 285 nodes and 367 pipes. PMID- 26563064 TI - Determination of Physico-chemical Parameters for Prediction of MSW Leachate Transport through Vadose Zone by Breakthrough Curve in a Realistic Undisturbed Soil Column. AB - The studies were carried out to find out transport parameters to predict leachate transport and contaminant plume profile underneath a municipal solid waste(MSW) dump. For this, both theoretical and practical avenues were explored. Batch experiments with disturbed soil were carried out with a tracer dye Brilliant Blue FCF to obtain the adsorption isotherm of the tracer. Column experiments with undisturbed realistic soil column were carried out to determine physico-chemical transport parameters using the tracer dye. MSW leachate transport were simulated and sensitivity analysis for MSW leachate transport was carried out for different Darcy velocity for pulse input.For determination of mass-transfer coefficient between the immobilized and mobilized water phase, we usedthe concept of number of transfer units (NTUs) and height of transfer units (HTUs) frequently used by Chemical Engineers. The obtained value of mass transfer coefficient calculated by this method was in excellent agreement with the value obtained from inverse calculation of parameter values by a standard software package (CXTFIT). PMID- 26563065 TI - Spectral Reflectance Properties of Gossypium hirsutum Leaves after Heavy Metal Toxicity. AB - The study demonstrated a link between heavy metal induced stress and optical properties of the leaves of Gossypium hirsutum. This work was conducted using the pot culture experiment. Three replications and four concentrations of Chromium (5%, 10%, 20% and 35%) with a control to assess the growth of plants were used. This experiment was conducted till 80 days. On 80th day the experiment was terminated and the leaves were plucked and air-dried. Portion of the air-dried, powdered cotton leaves was used for the Fourier Transformed Infra-Red (FT-IR) spectral analysis and the remaining portion was used for analyzing the biochemical constituents of the leaves (chlorophyll a, b, and total C and N contents). The Fourier Transformed Infra-Red spectrum indicated the aliphatic alcohol, inorganic bridge, C-OH stretch, C-H deformation, aromatic C=C stretch, OH stretch of H bond, aliphatic C-H stretch and OH stretch of aromatic C-H. The shifting and overlapping of the spectrum was observed after heavy metal induced toxicity when compared with that of the control spectra. This was supported by the biochemical analysis of chlorophyll a, b, and total carbon and nitrogen contents. This method was a preliminary study, which may be instrumental in developing optimal procedures for interpreting a particular stress of plants through analysis of their leaf reflectance spectrum. PMID- 26563066 TI - Optimal Modeling of Urban Ambient Air Ozone Concentration Based on Its Precursors' Concentrations and Temperature, Employing Genetic Programming and Genetic Algorithm. AB - Efficient models are required to predict the optimum values of ozone concentration in different levels of its precursors' concentrations and temperatures. A novel model based on the application of a genetic programming (GP) optimization is presented in this article. Ozone precursors' concentrations and run time average temperature have been chosen as model's parameters. Generalization performances of two different homemade models based on genetic programming and genetic algorithm (GA), which can be used for calculating theoretical ozone concentration, are compared with conventional semi-empirical model performance. Experimental data of Mashhad city ambient air have been employed to investigate the prediction ability of properly trained GP, GA, and conventional semi-empirical models. It is clearly demonstrated that the in-house algorithm which is used for the model based on GP, provides better generalization performance over the model optimized with GA and the conventional semi-empirical ones. The proposed model is found accurate enough and can be used for urban air ozone concentration prediction. PMID- 26563067 TI - Arsenic Removal and Its Chemistry in Batch Electrocoagulation Studies. AB - The aim of this study was to evaluate the impact of different oxidizing agents like light, aeration (by mixing) and electrocoagulation (EC) on the oxidation of As (III) and its subsequent removal in an EC batch reactor. Arsenic solutions prepared using distilled water and groundwater were evaluated. Optimum pH and the effect of varying initial pH on As removal efficiency were also evaluated. MaximumAs (III) removal efficiency with EC, light and aeration was 97% from distilled water and 71% from groundwater. Other results show that EC alone resulted in 90% As removal efficiency in the absence of light and mixing from distilled water and 53.6% from groundwater. Removal with light and mixing but without EC resulted in only 26% As removal from distilled water and 29% from groundwater proving that electro-oxidation and coagulation were more effective in removing arsenic compared to the other oxidizing agents examined. Initial pH was varied from 5 to 10 in distilled water and from 3 to 12 in groundwater for evaluating arsenic removal efficiency by EC. The optimum initial pH for arsenic removal was 7 for distilled water and groundwater. For all initial pHs tested between 5 and 10 in distilled water, the final pH ranged between 7 and 8 indicating that the EC process tends towards near neutral pH under the conditions examined in this study. PMID- 26563068 TI - Induction of Pectinase Hyper Production by Multistep Mutagenesis Using a Fungal Isolate--Aspergillus flavipes. AB - Aspergillus flavipes, a slow growing pectinase producing ascomycete, was isolated from soil identified and characterised in the previously done preliminary studies. Optimisation studies revealed that Citrus peel--groundnut oil cake [CG] production media is the best media for production of high levels of pectinase up to 39 U/ml using wild strain of A. flavipes. Strain improvement of this isolated strain for enhancement of pectinase production using multistep mutagenesis procedure is the endeavour of this project. For this, the wild strain of A. flavipes was treated with both physical (UV irradiation) and chemical [Colchicine, Ethidium bromide, H2O2] mutagens to obtain Ist generation mutants. The obtained mutants were assayed and differentiated basing on pectinase productivity. The better pectinase producing strains were further subjected to multistep mutagenesis to attain stability in mutants. The goal of this project was achieved by obtaining the best pectinase secreting mutant, UV80 of 45 U/ml compared to wild strain and sister mutants. This fact was confirmed by quantitatively analysing 3rd generation mutants obtained after multistep mutagenesis. PMID- 26563069 TI - Electrochemical Treatment of Textile Dye Wastewater by Mild Steel Anode. AB - This paper presents the results of the treatment of textile dye wastewater generated from a textile processing industry by electrochemical method. Experiments were conducted at current densities of 12, 24 and 48 A/m2 using mild steel as anode and cathode. During the various stages of electrolysis, parameters such as COD, color and BOD5 were determined in order to know the feasibility of electrochemical treatment. It was observed that increasing the electrolysis time and increased current density bring down the concentration of pollutants. Also COD removal rate and energy consumption during the electrolysis were calculated and presented in this paper. The present study proves the effectiveness of electrochemical treatment using MS as anode for TDW oxidation. PMID- 26563070 TI - Biosorption of Lead from Wastewater Using Fresh Water Algae Chlorella. AB - The potential use of fresh water algae Chlorella to sorb lead ions from wastewater was evaluated in this study. Fourier transform infra-red analysis of algal species revealed the presence of amino, carboxylic, hydroxyl and carbonyl groups, which were responsible for biosorption of lead ions. Batch sorption experiments were performed to determine the effects of contact time, biosorbent dosage and pH on the adsorption of Pb2+ ions. The optimum conditions of biosorbent dosage, pH and contact time were found to be l0 g/L, 5 and 100 min respectively. The applicability of the Langmuir and Freundlich isotherms for representation of the experimental data was investigated. The adsorption of lead ions on the algae Chlorella fitted well with Freundlich isotherm with a very high correlation coefficient. PMID- 26563071 TI - Performance Evaluation of Effluent Treatment Plant Installed in a Typical Slaughter House. AB - A study was conducted to evaluate performance of effluent treatment plant installed in a typical slaughter house engaged in production of frozen meat. The results indicated that the treatment plant consisting of two stage activated sludge process followed by activated adsorption filter achieves TDS, BOD and COD removal efficiencies of 98.62 %, 99.48 % and 99.08 % respectively. The treated effluent with TSS of 53 mg/L, BOD of 19 mg//L and COD of 74 mg/L is used by the slaughter house for irrigation of eucalyptus plants. The paper covers production process, effluent characterisation, effluent treatment scheme and performance. PMID- 26563072 TI - Barriers and Prospects of Carbon Sequestration in India. AB - Carbon sequestration is considered a leading technology for reducing carbon dioxide (CO2) emissions from fossil-fuel based electricity generating power plants and could permit the continued use of coal and gas whilst meeting greenhouse gas targets. India will become the world's third largest emitter of CO2 by 2015. Considering the dependence of health of the Indian global economy, there is an imperative need to develop a global approach which could address the capturing and securely storing carbon dioxide emitted from an array of energy. Therefore technology such as carbon sequestration will deliver significant CO2 reductions in a timely fashion. Considerable energy is required for the capture, compression, transport and storage steps. With the availability of potential technical storage methods for carbon sequestration like forest, mineral and geological storage options with India, it would facilitate achieving stabilization goal in the near future. This paper examines the potential carbon sequestration options available in India and evaluates them with respect to their strengths, weakness, threats and future prospects. PMID- 26563073 TI - Modelling Soil Erosion in the Densu River Basin Using RUSLE and GIS Tools. AB - Soil erosion involves detachment and transport of soil particles from top soil layers, degrading soil quality and reducing the productivity of affected lands. Soil eroded from the upland catchment causes depletion of fertile agricultural land and the resulting sediment deposited at the river networks creates river morphological change and reservoir sedimentation problems. However, land managers and policy makers are more interested in the spatial distribution of soil erosion risk than in absolute values of soil erosion loss. The aim of this paper is to model the spatial distribution of soil erosion in Densu River Basin of Ghana using RUSLE and GIS tools and to use the model to explore the relationship between erosion susceptibility, slope and land use/land cover (LULC) in the Basin. The rainfall map, digital elevation model, soil type map, and land cover map, were input data in the soil erosion model developed. This model was then categorized into four different erosion risk classes. The developed soil erosion map was then overlaid with the slope and LULC maps of the study area to explore their effects on erosion susceptibility of the soil in the Densu River Basin. The Model, predicted 88% of the basin as low erosion risk and 6% as moderate erosion risk, 3% as high erosion risk and 3% as severe risk. The high and severe erosion areas were distributed mainly within the areas of high slope gradient and also sections of the moderate forest LULC class. Also, the areas within the moderate forest LULC class found to have high erosion risk, had an intersecting high erodibility soil group. PMID- 26563074 TI - Adsorption of Nickel (II) from Aqueous Solution by Bicarbonate Modified Coconut Oilcake Residue Carbon. AB - The adsorption of Ni (II) on modified coconut oilcake residue carbon (bicarbonate treated coconut oilcake residue carbon-BCORC) was employed for the removal of Ni (II) from water and wastewater. The influence of various factors such as agitation time, pH and carbon dosage on the adsorption capacity has been studied. Adsorption isothermal data could be interpreted by Langmuir and Freundlich equations. In order to understand the reaction mechanism, kinetic data has been studied using reversible first order rate equation. Similar studies were carried out using commercially available activated carbon--CAC, for comparison purposes. Column studies were conducted to obtain breakthrough capacities of BCORC and CAC. Common anions and cations affecting the removal of Ni (II) on both the carbons were also studied. Experiments were also done with wastewater containing Ni (II), to assess the potential of these carbons. PMID- 26563075 TI - Nanostructured Mn-Fe Binary Mixed Oxide: Synthesis, Characterization and Evaluation for Arsenic Removal. AB - Adsorption of arsenic on bimetallic Mn and Fe mixed oxide was carried out using both field as well as simulated water. The material was synthesized using hydrothermal method and characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Langmuir and Freundlich adsorption isotherms were computed using batch adsorption studies to determine the adsorption capacity of Mn-Fe binary mixed oxide for arsenic. Adsorption capacity for MFBMO obtained from Freundlich model was found to be 2.048 mg/g for simulated water and 1.084 mg/g for field water. Mn-Fe binary mixed oxide was found to be effective adsorbent for removal of arsenic from water. PMID- 26563076 TI - Hydrogeochemical Properties of Groundwater in Parts of Abakaliki City, Southeastern Nigeria. AB - This study is aimed at providing useful information about the hydrochemistry of some parts of Abakaliki city for proper understanding of the groundwater quality. Twelve representative groundwater samples from water boreholes/wells in the study area were analyzed for their hydrogeochemical properties: pH, Electrical Conductivity (EC), Turbidity, Total Dissolved Solids (TDS), Total Hardness (TH), COD, Ca2+, Mg2+, Na+, K+, HCO3-, SO4(2-), Cl-, NO3-, and CO3(2-). Aquifers in the study environment were located in the fractured shales of Abakaliki Formation. The composition of the major ions outlined the relationships between the aquifer chemistry. Strong positive correlations exist between EC-TDS, Na(+)-TDS, Mg(2+) SO4(2+) and Ca(2+)-SO4(2+). Piper trilinear diagram has also been utilized in data interpretation and to classify the hydrogeochemical facies. Majority of the analyzed samples were characterized by the dominance of Ca2+, Mg2+, SO4(2-) and Cl- and the Piper trilinear diagram indicated two water types: Ca (Mg)-Cl and Ca Mg-Na-Cl-SO4 water types. Na/Cl ratio ranging from 0.12 to 0.73 (all below 1.0) with a mean of 0.55 inferred fresh water existence. Results of this study generally showed that the analyzed groundwater samples pose no threat to human consumption, health and environment since the concentrations of the physico chemical parameters were within the WHO standards. PMID- 26563077 TI - Assessment of Surface Water Quality Using Multivariate Statistical Techniques in a Part of River Cauvery, Tamil Nadu, India. AB - The study explains water quality of the Cauvery River in the southern region of Peninsular India. Thirteen parameters including trace elements (Cd, As, Cu, Cr, Zn and Pb) have been monitored on 50 sampling points from a hydro-geochemical survey, conducted in the river stretch under study. Several water quality parameters showed considerable changes due to increased runoff from the catchments and other seasonal factors. Multivariate discriminant analysis delineated a few parameters responsible for temporal variation in water quality. Factor analysis (FA) identified three factors responsible for data structure explaining 91% of total variance in surface water. It allowed grouping selected parameters according to common features. The results indicated that point source pollutants primarily affected the water quality of this region. This study indicates the necessity and usefulness of multivariate statistical techniques for evaluation and interpretation of the data. It facilitates better information about the water quality and designs some remedial techniques to prevent future contamination. PMID- 26563078 TI - Study of Hydro-Chemical Groups of Groundwater in Different Geomorphic and Geological Settings of Sarada River Basin, Andhra Pradesh. AB - An attempt has been made to study the hydrochemistry of groundwater in Sarada River Basin (SRB).The groundwater samples were collected from dug wells and bore wells which have been analysed for cations and anions in the study area. The river basin is divided into six sub-basins for the purpose of study. The six hydrochemical groups namely sodium bicarbonate, magnesium bicarbonate, sodium chloride, calcium bicarbonate, sodium sulphate, and magnesium chloride, according to their dominant cations and anions were observed and studied in different types of rock formations, soil groups, geomorphic settings, slopes and groundwater aquifers in the area of the investigation. The hydrochemical data indicated that the groundwater was contaminated in the southern part of lower Sarada River Basin by sub-surface sea water intrusion, pollution due to the industrial wastes discharged by existing sugar factories and chemical contamination due to over use of fertilizers and pesticides in the areas of intense irrigation could be identified. In many locations maximum parameters were within the permissible limits and some were beyond the limits of drinking water standards. However, most of the groundwater of the SRB is found suitable for drinking, irrigation, and industrial purposes. PMID- 26563079 TI - Assessment of Groundwater Quality for Irrigation in Coimbatore South Taluk, Coimbatore District, Tamil Nadu. AB - The study was conducted to evaluate the suitability of ground water for irrigation purpose at twenty seven locations in Coimbatore South Taluk, Coimbatore District. The analytical result shows that Na and Cl are the dominant cation and anions respectively in the groundwater. The values of TDS and EC exceed the permissible limits at some locations due to increase in ionic concentrations. Based on SAR, RSC, US Salinity diagram and Wilcox diagram it is observed that the water ranges from excellent to good quality in most of the places and can be used for irrigation without any hazard. Gibbs variation diagram indicates that lithology is main controlling factor for water chemistry. However, the high SAR and RSC values at few locations restrict suitability for irrigation purpose. PMID- 26563080 TI - Seasonal Variation of Groundwater Quality in Erode District, Tamil Nadu, India. AB - In recent years, the recurring environmental issues regarding hazardous waste, global climate change, stratospheric ozone depletion, groundwater contamination, disaster mitigation and removal of pollutant have become the focus of environmental attention. In the management of water resources, quality of water is just as important as its quantity. In order to assess the quality and/or suitability of groundwater for drinking and irrigation in Erode District, 144 water samples each in post-monsoon and pre-monsoon during the year 2007 were collected and analyzed for various parameters. These parameters were compared with IS: 10500-1991 drinking water standards. Out of 144 samples, 29 samples exceeded the permissible limit for both the monsoons, 71 samples were within the permissible limit for both the monsoons and the remaining samples exceeded the permissible limit for any one of the monsoon. During both monsoons, except some samples, most of the samples were suitable for drinking and irrigation. PMID- 26563081 TI - Characterization of Wastewater Effluents Releasing from Slaughterhouses in and around Hyderabad City (India). AB - The present study was undertaken to determine the pollution load to the environment causing by the wastewater effluents releasing from organized and unorganized slaughterhouses in and around Hyderabad city. The wastewater effluents collected from three slaughterhouses, at the sites of releasing out to the surrounding environment,were characterized in terms of physico-chemical and microbiological parameters. The physico-chemical parameters, such as temperature, pH, alkalinity, turbidity, total suspended solids, electrical conductivity, total dissolved solids, dissolved oxygen, biological oxygen demand, chemical oxygen demand, total organic carbon, calcium, NH4-N, nitrates and phosphates were estimated in the wastewater effluents collected from three different slaughterhouses. The heavy metals, such as lead, nickel and cadmium contents were detected. The microbiological characteristics, such as total viable count, total coliform count recorded and also the pathogens of public health significance, such as Salmonella spp., Shigella spp., Streptococcus faecalis, Staphylococcus aureus, Bacillus cereus and Listeria monocytogenes were isolated and identified. The results revealed significantly much higher values of almost all pollution parameters both physicochemical and microbiological of wastewater effluents collected from three slaughterhouses, and these values exceeding the effluent discharge standards for releasing the effluents into public sewers and inland surface waters, recommended by the pollution control board. The slaughterhouses must maintain the wastewater collection and treatment facilities and modify the existing treatment systems in order to comply the general effluents discharge standardsrecommended by the pollution control board. PMID- 26563082 TI - Effect of Increasing Concentrations of Chromium on Soil Enzymatic Activities and Soil Respiration. AB - The effects of various concentrations of chromium on the activity of dehydrogenase, catalase and soil respiration were studied after 14, 28, 56 and 112 days of incubation period. Chromium was applied as K2Cr2O7 in the amounts of 0, 25, 50, 100, 200, 400, 800 ig g(-1) of soil. Soil contamination with Cr decreased the activity of dehydrogenase, catalase and soil respiration. About 36.92% and 44.88% inhibition in the activity of dehydrogenase was caused by 50 and 100 ig g(-1) Cr addition respectively, after 14 days of incubation. Catalase activity significantly (P < 0.001) decreased with applied doses of chromium after 14 days of incubation. A significant inhibition in soil respiration was observed after 56 days of incubation with applied doses of chromium. These results suggest that soil respiration, dehydrogenase and catalase enzyme activities are suitable parameters for the toxicity test. PMID- 26563083 TI - Concentrations of Volatile Organic Compound (Styrene) in an Industrial Area of Agra, India. AB - Volatile organic compounds (VOCs) are major group of air pollutants which play critical role in atmospheric chemistry. These contribute to toxic oxidants which are harmful to ecosystem, human health and atmosphere. A sampling program was conducted to determine the ambient VOC levels in the city of Agra (Uttar Pradesh), India during day time and overnight in 2010. Sampling sites were selected at three industrial area of Agra. Samples were analyzed for styrene. Concentration of Styrene was determined at different sampling points in the air of Agra in order to investigate their spatial distributions. The vertical motions of air masses also had a large impact on the variations of the level of VOC. The inter-species ratios exhibit clear seasonal variation indicating deferential reactivity of the VOCs species in different seasons. PMID- 26563084 TI - The Comparative Evaluation of the Performance of Two Phytoremediation Systems for Domestic Wastewater Treatment. AB - The constructed wetlands as well engineered techniques have been used effectively for phytoremediation of wastewater and pollution control during the last decades. In these technologies, the naturally occurring processes of plants alongside micro-organisms present in the bio-film attached to the roots, soil substrate and water column degrade the organic pollutants. The study seeks to compare the potential use of Phragmites sp. reed bed and floating macrophyte water hyacinth (Eichhornia crassipes) system for domestic wastewater treatment. The sewage treatment performance is evaluated as 80% & 76% chemical oxygen demand (COD), 90% & 87% biological oxygen demand (BOD5), 24% & 18% total dissolved solids (TDS), 69% & 67% total suspended solids (TSS), 12% & 5% Chlorides, 73% & 69% ammonia nitrogen (NH3-N), 42% & 31% phosphate (PO4-P), 93% & 91% most probable number (MPN) and 95% & 92% total viable count (TVC) reduction at optimum hydraulic retention time (HRT) of 24 & 43 h in Phragmites sp. and water hyacinth systems, respectively. Likewise, the floating macrophyte pond contrary to reed bed process shows insignificant pollutant diminution at 24 h HRT. This paper also highlights the microbial population present through the wetland systems by estimation of total viable count (TVC). The botanical aspect with reference to the plant growth is shown a significant increase in vegetation yield. The overall studies indicate the better treatment efficiency by preferred Phragmites sp. root zone system at low foot print area for domestic wastewater. PMID- 26563085 TI - Phytoremediation of Petroleum Hydrocarbon (PHC) Contaminated Soil by Using Mimosa pudica L. . AB - The aim of this study was to evaluate the efficiency of Mimosa pudica L. that could be effective in phytoremediation of PHC-contaminated soil. Experiments were conducted in net house to determine the tolerance of this species to a heavy crude oil contaminated soil under the application of two fertilizer levels and reduction of PHC was monitored for 180 days. Assessment of plant growth, biomass and Total Oil and Grease (TOG) degradation were carried out at an interval of 60 days. In the presence of contaminants, biomass and plant height were reduced up to 27% and 10.4% respectively. Experiments with different percentages of crude oil showed that M. pudica could tolerate crude-oil contamination up to 6.2% (w/w). The estimation of TOG in soil of the tested plants revealed that M. pudica could decrease 31.7% of crude oil contaminants in low fertilizer level (200N, 100P, 100K) and 24.7% in high fertilizer level (240N, 120P, 120K). In case of unplanted pots, the reduction of TOG was 13.7% in low fertilizer level and 11.2% in high fertilizer level. This experiment has identified the suitability of a native candidate plant species for further investigation of their phytoremediation potential. PMID- 26563086 TI - Optimisation of Environmental Conditions for Enhanced Production of Fungal Exopectinase Using Agro-industrial Wastes. AB - Management of household solid waste and agro industrial residues generated from various sources is a serious problem due to huge ever increasing population and pollution. Application of these worthless agro waste materials to generate a commercially valuable product, pectinase enzyme, using locally isolated fungal strain, Aspergillus flavipes, was the main motive of this study. Physiological characterisation and enzyme profile determination were done along with formulation of production media. Fruit skins, rags were used as C source and oil cakes were used for N source. Various combinations of these C and N sources were applied for revised production of pectinase enzyme compared to YEP basal media (29 U/ml). A huge increase in pectinase production of 40 U/ml was obtained with Citrus peel - Sesame oil cake (CS) media. The enzyme had its maximum activity at 500C, 4.5 pH. This was achieved at 45 min in 1.5% substrate concentration. PMID- 26563087 TI - Decolorization of Sulphonated Azodye Metanil Yellow by Newly Isolated Bacterial Strain: Bacillus -3330. AB - Newly isolated, Bacillus sp. MTCC-3330 was screened for the decolorization of a sulphonated azodye metanil yellow under aerobic conditions. 100% decolorization was observed of Metanil Yellow at 0.01mM, 0.02mM 0.05mM concentrations within 30h, 35h and 45h respectively. Decolorization was confirmed by UV-VIS spectrophotometer. The initial dye solution showed highest peak at the wavelength of 437 nm (lambdamax of the Metanil Yellow). The decolorized dye showed disappearance of peak, which indicated that the decolorization is due to dye degradation. The bacterium sp. also decolorized the another azodye Methyl Orange. PMID- 26563088 TI - Experimental Studies on Co-composting of Municipal Solid Waste with Paper Mill Sludge. AB - In this study, a series of experimental studies were conducted with regard to bioconversion of organic fraction of municipal solid waste along with paper mill sludge at different C/N ratios. About 10 kg of shredded waste containing paper mill sludge, saw dust and municipal solid waste was placed in reactors in different proportions and 100 mL of effective microorganisms was added to it. The variation in physical and chemical parameters was monitored throughout the process. The results indicate that co-composting of paper mill sludge with municipal solid waste produces compost that is more stable and homogenous and can be effectively used as soil conditioner. PMID- 26563089 TI - Vermicomposting of Solid Waste Using Local and Exotic Earthworms: A Comparative Study. AB - The aim of this study was to assess the decomposition efficiency of earthworms, local (L.mauritii) as well as exotic (Eisenia foetida) in vermicomposting of garden litter in SRM University campus. The vermicompost produced through vermicomposting of garden litter mixed with cow dung in the ratio of 3:1 by using local and exotic earthworms (Eisenia foetida) was rich in ammoniacal nitrogen, nitrate nitrogen, available phosphorus, total potassium and TKN, and there was a reduction in total organic carbon and carbon to nitrogen ratio. The study reveals that the decomposition efficiency of exotic earthworms is better compared to local earthworms. PMID- 26563090 TI - Air Quality Indices: A Literature Review. AB - Air quality indices are commonly used to indicate the level of severity of air pollution to the public. It is infeasible and perhaps impossible to formulate a universal technique for determining air quality index, one that considers all pollutants and that is appropriate for all situations. The intended use of the air quality index is to identify the vulnerable zone. There are mainly two approaches viz. single pollutant index and multi-pollutant index to determine the air quality index. Every index has its own characteristic strengths and weaknesses that affect its suitability for particular applications. This paper attempts to present a review of all the major air quality indices developed worldwide. PMID- 26563092 TI - Vision problems in ischaemic stroke patients: effects on life quality and disability. AB - BACKGROUND AND PURPOSE: Vision problems after cerebral infarction are an increasingly acknowledged problem. Our aim was to investigate the effect on quality of life and post-stroke disability. METHODS: Patients admitted to the Stroke Unit, Department of Neurology, Haukeland University Hospital, between February 2006 and July 2008 with acute cerebral infarction were prospectively registered in the NORSTROKE Registry. Patients received a postal questionnaire at least 6 months after stroke. The questionnaire included 15D(c), EuroQol 5D (EQ 5D(TM) ), the Hospital Anxiety and Depression Scale (HADS), the Fatigue Severity Scale (FSS) and the Barthel Index (BI). RESULTS: Of 328 responders, 83 (25.4%) reported a vision problem. Vision problems were associated with older age (71.8 years vs. 66.5 years, P = 0.001), higher National Institutes of Health Stroke Scale score on admission (5.9 vs. 3.8, P < 0.001), higher modified Rankin Scale day 7 (2.0 vs. 1.4, P < 0.001) and lower BI day 7 (85.7 vs. 93.9, P = 0.002). Patients with vision problems had lower median EQ-5D utility score (0.62 vs. 0.80, P < 0.001), lower median 15D utility score (0.73 vs. 0.89, P < 0.001), higher median HADS score (12 vs. 5, P < 0.001), higher median FSS score (5.6 vs. 4.3, P < 0.001) and lower median BI (95 vs. 100, P < 0.001) on long-term follow up. Patients with self-reported vision problems scored lower on all sub-scores of BI on follow-up (all P < 0.001). CONCLUSION: One in four patients reported a vision problem on follow-up after cerebral infarction. Vision problems after cerebral infarction reduce quality of life and are associated with increased disability. Thorough diagnostic evaluation and targeted rehabilitation is important. PMID- 26563091 TI - Quantification of tumor fluorescence during intraoperative optical cancer imaging. AB - Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 +/- 0.6, 2.4 +/- 0.3, 2.6 +/- 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 +/- 0.2 vs. 4.3 +/- 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 +/- 11.5, 5.1 +/- 1.8, 4.1 +/- 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 +/- 3.4 vs. 2.4 +/- 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth. PMID- 26563093 TI - Radiological imaging in acute ischaemic stroke. AB - Patients who suffer acute ischaemic stroke can be treated with thrombolysis if therapy is initiated early. Radiological evaluation of the intracranial tissue before such therapy can be given is mandatory. In this review current radiological diagnostic strategies are discussed for this patient group. Beyond non-enhanced computed tomography (CT), the standard imaging method for many years, more sophisticated CT stroke protocols including CT angiography and CT perfusion have been developed, and additionally an increasing number of patients are examined with magnetic resonance imaging as the first imaging method used. Advantages and challenges of the different methods are discussed. PMID- 26563095 TI - Disability, anxiety and depression in patients with medication-overuse headache in primary care - the BIMOH study. AB - BACKGROUND AND PURPOSE: Medication-overuse headache (MOH) is common in the general population. Detoxification is the general treatment principle for MOH. The present paper is based on a study of a brief intervention (BI) for MOH in primary care. New data on headache disability and the Hospital Anxiety and Depression Scale (HADS) for MOH patients compared to population controls with and without chronic headache are presented and compared to previously published main outcome data. METHODS: This was a double-blind pragmatic cluster randomized controlled trial carried out amongst 50 general practitioners in Norway. The BI was compared to business as usual (BAU) and population controls, and patients were followed up after 3 months. Primary outcomes were headache and medication days per month after 3 months. Headache disability and HADS were also measured as secondary outcomes. RESULTS: Sixty MOH patients and 40 population controls were included. BI was significantly better than BAU after 3 months regarding primary outcomes. Non-intervention population controls did not change. The MOH patients had significantly higher headache disability and anxiety scores than the population controls. CONCLUSIONS: Patients with MOH are a highly disabled group where anxiety and depression are important comorbidities. Detoxification of MOH by a BI in primary care is effective and has potential for saving resources for more treatment-resistant cases in neurologist care. PMID- 26563094 TI - Disease-modifying treatments for multiple sclerosis - a review of approved medications. AB - BACKGROUND AND PURPOSE: There is still no curative treatment for multiple sclerosis (MS), but during the last 20 years eight different disease-modifying compounds have been approved for relapsing-remitting MS (RRMS). METHODS: A literature search was conducted on published randomized controlled phase III trials indexed in PubMed on the approved medications until 21 May 2015. RESULTS: In this review the mode of action, documented treatment effects and side effects of the approved MS therapies are briefly discussed. CONCLUSIONS: Based on current knowledge of risk-benefit of the approved MS medications, including factors influencing adherence, it is suggested that oral treatment with dimethyl fumarate or teriflunomide should be preferred as a starting therapy amongst the first-line preparations for de novo RRMS. In the case of breakthrough disease on first-line therapy, or rapidly evolving severe RRMS, second-line therapy with natalizumab, fingolimod or alemtuzumab should be chosen based on careful risk-benefit stratification. PMID- 26563096 TI - The investigation of inborn errors of metabolism as an underlying cause of idiopathic intellectual disability in adults in Norway. AB - BACKGROUND AND PURPOSE: Inborn errors of metabolism (IEMs) may be an unrecognized cause of intellectual disability (ID) in adults. Knowledge and techniques for investigating IEMs have evolved rapidly; therefore adult patients with idiopathic ID may benefit from an up-to-date aetiological work-up. This review aims at establishing recommendations for investigating IEMs as a cause of ID in adults. METHODS: PubMed was searched for articles published between 2000 and 2015 regarding clinical work-up, IEMs, ID and adults. Information compiled from 61 articles is used to give practical suggestions from a clinical point of view. RESULTS: Many IEMs that cause ID are characterized by increased risk of specific somatic, neurological and psychiatric signs. Neurometabolic investigations of ID should start with a thorough medical history, clinical examination and general screening in blood. Brain imaging with magnetic resonance imaging and if possible magnetic resonance spectroscopy should also be part of the initial work-up. The aim is to detect abnormalities that give clues to a specific IEM. After the initial screening, a first tier of neurometabolic screening tests in blood and urine should be performed. If this fails to give diagnostic clues, a second tier of neurometabolic tests should be considered in order to secure that the treatable IEMs are detected. Whole exome sequencing techniques, when they become available in clinical settings, will offer new opportunities for detection of IEMs. CONCLUSION: Based on a broad review of the current literature a systematic diagnostic work-up to detect IEMs as a cause of ID in adults is suggested. PMID- 26563097 TI - Roles for SUMO in pre-mRNA processing. AB - When the small ubiquitin-like modifier (SUMO)-1 protein is localized on the genome, it is found on proteins bound to the promoters of the most highly active genes and on proteins bound to the DNA-encoding exons. Inhibition of the SUMO-1 modification leads to reductions in initiation of messenger RNA (mRNA) synthesis and splicing. In this review, we discuss what is known about the SUMOylation of factors involved in transcription initiation, pre-mRNA processing, and polyadenylation. We suggest a mechanism by which SUMO modifications of factors at the promoters of high-activity genes trigger the formation of an RNA polymerase II complex that coordinates and integrates the stimulatory signals for each process to catalyze an extremely high level of gene expression. WIREs RNA 2016, 7:105-112. doi: 10.1002/wrna.1318 For further resources related to this article, please visit the WIREs website. PMID- 26563098 TI - Lung ultrasound is a reliable method for evaluating extravascular lung water volume in rodents. AB - BACKGROUND: Lung ultrasound (LUS) can diagnose extravacular lung water (EVLW) through the visualization of B lines in both humans and large animals. However, there are no published data on the use of ultrasound to detect EVLW in rats, the gold standard to evaluate of EVLW in rats is post-mortem gravimetric analysis. The present study was designed to determine the similarity between lung sonography and gravimetric measurements of EVLW in rats in an acute lung injury (ALI) model. METHODS: Thirty male Sprague-Dawley rats were randomized into control and experimental groups. The B lines were measured byLUS at baseline. ALI was induced by the intravenous administration of oleic acid (OA) at a dose of 9 ul/100 mg, and controls were injected the same amount of isotonic saline. After 1 h, B-lines were measured by LUS in each rat following the induction of ALI. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio according to the standard gravimetric methodology. Lung samples from three rats in each group were examined histologically. RESULTS: B-lines were present in all rats from experimental group at 1 h point after OA injection. The statistical correlation between the two methods of assessing EVLW provided an r = 0.834 (p < 0.001). Repeatability studies of the LUS technique (Bland-Altman plots) showed good intra-observer and inter-observer reproducibility. CONCLUSION: The data suggest that, in an experimental rat model of ALI, B lines score as assessed by LUS can provide an easy, semi-quantitative, noninvasive. Real-time index of EVLW which is strongly correlated to experimental gravimetric assessments. PMID- 26563099 TI - Mechanical and microstructural properties of fixation systems used in oral and maxillofacial surgery. AB - OBJECTIVES: This paper aims to evaluate in vitro the mechanical and microstructural properties of internal fixation systems used in oral and maxillofacial surgeries. MATERIALS AND METHODS: Four brands of internal fixation systems (screws and 4-hole straight plates) were selected and assigned to four groups: G1 Leibinger(r), G2 Toride(r), G3 Engimplan(r), and G4 Medartis(r). The systems were submitted to Vickers hardness testing, metallographic and interstitial elements chemical composition analyses. Data were submitted to ANOVA and Tukey's test for statistical analysis. RESULTS: Plates in groups 1, 2, and 3 showed similar microstructure and mechanical properties, different from those in G4 revealing larger grains. In all groups, the screws showed similar microstructure, with uniform arrangement and size of grains; the screws showed higher hardness values than those observed for the plates. CONCLUSIONS: The results indicate that all materials tested are adequate for use in oral maxillofacial surgeries. PMID- 26563100 TI - Protocol for systematic review of evidence on the determinants and influence of early glycaemic control in childhood-onset type 1 diabetes. AB - BACKGROUND: Landmark studies in adult-onset type 1 diabetes (T1D) populations indicate that improved glycaemic control through use of intensive insulin therapy is strongly associated with reduced risk for the development of diabetes-related complications and mortality in later years. However, it is unclear whether these associations can be extrapolated to childhood-onset T1D, given the influence of other important biological and psychosocial determinants of glycaemic control, particularly during adolescence. The aims of the review are (1) to investigate the impact of early glycaemic control (within the first 2 years after diagnosis) on subsequent glycaemic trends and risk of complications during the life course of childhood-onset T1D and (2) to identify the predictors of early glycaemic control in children and young people (0-25 years). METHODS: The methods used in this study are systematic identification, review and mapping of quantitative (intervention and observational) and qualitative literature; assessing the effect and predictors of early glycaemic control in T1D (diagnosed <=18 years) on risk or prevalence of later complications. An iterated search strategy, with no language or period restrictions, was applied to identify studies from six electronic databases. This will be supplemented by hand-searching (reference lists and contacting authors of studies meeting the inclusion criteria). Studies assessing glycaemic control within the first 2 years of diagnosis in children (at baseline) will be quality-assessed against predefined criteria and mapped descriptively to future health outcomes. Extracted data will be analysed and synthesised using narrative and forest plots or harvest plots for quantitative evidence and thematic analyses for qualitative studies. To get a deeper understanding of the predictors of early glycaemic control in reducing complications in childhood and adult life, we will integrate qualitative and quantitative evidence using mixed methods or parallel synthesis approach. DISCUSSION: These linked reviews will be the first to systematically investigate the effects of early glycaemic control and integrate both the quantitative and qualitative evidence on predictors of early glycaemic control in childhood-onset T1D in reducing future diabetes complications. This will help identify and map current research and inform development of effective future interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024546. PMID- 26563101 TI - Mapping 3D Strains with Ultrasound Speckle Tracking: Method Validation and Initial Results in Porcine Scleral Inflation. AB - This study aimed to develop and validate a high frequency ultrasound method for measuring distributive, 3D strains in the sclera during elevations of intraocular pressure. A 3D cross-correlation based speckle-tracking algorithm was implemented to compute the 3D displacement vector and strain tensor at each tracking point. Simulated ultrasound radiofrequency data from a sclera-like structure at undeformed and deformed states with known strains were used to evaluate the accuracy and signal-to-noise ratio (SNR) of strain estimation. An experimental high frequency ultrasound (55 MHz) system was built to acquire 3D scans of porcine eyes inflated from 15 to 17 and then 19 mmHg. Simulations confirmed good strain estimation accuracy and SNR (e.g., the axial strains had less than 4.5% error with SNRs greater than 16.5 for strains from 0.005 to 0.05). Experimental data in porcine eyes showed increasing tensile, compressive, and shear strains in the posterior sclera during inflation, with a volume ratio close to one suggesting near-incompressibility. This study established the feasibility of using high frequency ultrasound speckle tracking for measuring 3D tissue strains and its potential to characterize physiological deformations in the posterior eye. PMID- 26563102 TI - Comparing databases: determinants of sexually transmitted infections, HIV diagnoses, and lack of HIV testing among men who have sex with men. AB - BACKGROUND: Early detection and treatment of STI/HIV are public health priorities. Our objective was to compare characteristics of men who have sex with men (MSM) in Dutch data available in 2010 from EMIS, an international internet survey, Schorer Monitor, a Dutch internet survey, and data from STI- clinic visits, since these might be subject to different and unknown biases. METHODS: Data from Dutch MSM Internet Surveys (EMISNL N = 3,787; Schorer Monitor, SMON N = 3,602), and 3,800 STI clinic visits (SOAP) were combined into one dataset. We included factors that were measured in all three databases. The socio demographics included were age (at the time of the survey), zip code, and ethnicity. Behavioural variables included were the number of sexual partners, condom use with last sexual partner, drug use, being diagnosed with STI, being diagnosed with HIV, and HIV testing. Outcomes we investigated were being diagnosed with STI, HIV, and never been tested for HIV. RESULTS: Logistic regressions showed that determinants for being diagnosed with STI were having more sexual partners, drug use, and having had an HIV test (aORs 1.3 to 17.1) in EMIS and SMON. Determinants for being diagnosed with HIV in all three databases were older age, living in Amsterdam, and having more partners (aORs 1.8 to 4.4). In EMIS and SMON, drug use, non-condom use, and having STI were additional determinants (aORs 1.6 to 8.9). Finally, determinants associated with never been tested for HIV were being younger (only SOAP), living outside of Amsterdam, having fewer partners, no drug use, and no STI (aORs 0.2 to 0.8). CONCLUSIONS: Risk factors from internet surveys were largely similar, but differed from STI clinics, possibly because it involves self-reports rather than diagnoses or because of differences in timing. The difference between the internet surveys and STI clinic data is much less pronounced for having never been tested, suggesting both are appropriate for this outcome. These findings shed light on conclusions drawn from different data sources, as well as the comparability of recruitment strategies, the robustness of risk factors, consequences of phrasing questions differently, and on (policy) implications based on different data sources. PMID- 26563103 TI - [An unusual tongue swelling]. PMID- 26563104 TI - Letter to the Editor on "Implementation of Network for the Improvement of Addiction Treatment (NIATx) Processes in Substance Use Disorder Treatment Centers". PMID- 26563105 TI - Extracellular matrix remodeling in wound healing of critical size defects in the mitral valve leaflet. AB - The details of valvular leaflet healing following valvuloplasty and leaflet perforation from endocarditis are poorly understood. In this study, the synthesis and turnover of valvular extracellular matrix due to healing of a critical sized wound was investigated. Twenty-nine sheep were randomized to either CTRL (n = 11) or HOLE (n = 18), in which a 2.8-4.8 mm diameter hole was punched in the posterior mitral leaflet. After 12 weeks, posterior leaflets were harvested and histologically stained to localize extracellular matrix components. Immunohistochemistry was also performed to assess matrix components and markers of matrix turnover. A semi-quantitative grading scale was used to quantify differences between HOLE and CTRL. After 12 weeks, the hole diameter was reduced by 71.3 +/- 1.4 % (p < 0.001). Areas of remodeling surrounding the hole contained more activated cells, greater expression of proteoglycans, and markers of matrix turnover (prolyl 4-hydroxylase, metalloproteases, and lysyl oxidase, each p <= 0.025), along with fibrin accumulation. Two distinct remodeling regions were evident surrounding the hole, one directly bordering the hole rich in versican and hyaluronan and a second adjacent region with abundant collagen and elastic fiber turnover. The remodeling also caused reduced delineation between valve layers (p = 0.002), more diffuse staining of matrix components and markers of matrix turnover (p < 0.001), and disruption of the collagenous fibrosa. In conclusion, acute valve injury elicited distinct, heterogeneous alterations in valvular matrix composition and structure, resulting in partial wound closure. Because these changes could also affect leaflet mechanics and valve function, it will be important to determine their impact on healing wounds. PMID- 26563106 TI - Volume elastic modulus of the brachial artery and coronary artery stenosis in patients with suspected stable coronary artery disease. AB - This study aimed to examine the association between the non-invasive measurement of the brachial artery volume elastic modulus (V E), an index of arterial stiffness, and the presence of coronary artery stenosis in patients with suspected stable coronary artery disease (CAD). A total of 135 patients with suspected stable CAD (87 men, mean age, 64 +/- 12 years) underwent oscillometric measurement of the brachial artery to obtain V E. Coronary angiography was thereafter carried out to diagnose CAD, defined as having >=75 % stenosis in the epicardial coronary arteries. V E was significantly higher in patients with CAD (1.94 +/- 0.34 mmHg/%) than in those without CAD (1.71 +/- 0.35 mmHg/%, P < 0.001). In multiple logistic regression analysis, V E was an independent predictor for the presence of CAD (odds ratio 1.19 per 0.1 mmHg/% increase, 95 % CI 1.04-1.51) even after adjusting for multiple potential confounders including the Framingham risk score (FRS). The area under the curve of the receiver operating characteristic curve analysis for discriminating CAD increased significantly after the addition of V E to the FRS (from 0.75 to 0.81, P = 0.034). The category-free net reclassification improvement and the integrated discrimination improvement by adding V E to the FRS were 0.476 (95 % CI 0.146 0.806) and 0.086 (95 % CI 0.041-0.132), respectively. In conclusion, the brachial V E was significantly associated with the presence of coronary artery stenosis. The additional measurement of V E to the FRS improved the ability to identify patients with coronary artery stenosis among those with suspected stable CAD. PMID- 26563107 TI - A practical approach for a patient-tailored dose protocol in coronary CT angiography using prospective ECG triggering. AB - To derive and validate a practical patient-specific dose protocol to obtain an image quality, expressed by the image noise, independent of patients' size and a better radiation dose justification in coronary CT angiography (CCTA) using prospective ECG triggering. 43 patients underwent clinically indicated CCTA. The image noise, defined as the standard deviation of pixel attenuation values in a homogeneous region in the liver, was determined in all scans. Subsequently, this noise was normalized to the radiation exposure. Next, three patient-specific parameters, body weight, body mass index and mass per length (MPL), were tested for the best correlation with normalized image noise. From these data, a new dose protocol to provide a less variable image noise was derived and subsequently validated in 84 new patients. The normalized image noise increased for heavier patients for all patients' specific parameters (p < 0.001). MPL correlated best with the normalized image noise and was selected for dose protocol optimization. This new protocol resulted in image noise levels independent of patients' MPL (p = 0.28). A practical method to obtain CCTA images with noise levels independent of patients' MPL was derived and validated. It results in a less variable image quality and better radiation exposure justification and can also be used for CT scanners from other vendors. PMID- 26563108 TI - Myomectomy at the time of cesarean delivery. AB - INTRODUCTION: Myomectomy at the time of cesarean delivery has been traditionally discouraged. Recent literature has challenged this view. We present two cases of large subserosal fibroids that underwent removal without complication at the time of cesarean delivery. MATERIALS AND METHODS: We present two patients that underwent myomectomy at the time of cesarean delivery. Case 1 had a 10 cm subserosal leiomyoma removed without complication at the time of a cesarean section for breech presentation. Case two had a fundal myoma removed without incident at the time of primary cesarean delivery for suspected macrosomia. DISCUSSION: Myomectomy at the time of cesarean section has been traditionally discouraged. Recent studies have questioned this recommendation and demonstrated no significant increase in peri-operative complications when myomectomy is performed at the time cesarean section. Further, there is added benefit in that a future procedure is avoided. CONCLUSION: Myomectomy at the time of cesarean delivery is both a safe and reasonable procedure. PMID- 26563109 TI - Nutrition education in the medical school curriculum: a review of the course content at the Royal College of Surgeons in Ireland-Bahrain. AB - BACKGROUND: Only 14 % of American physicians report that they feel adequately trained to provide nutritional counselling. The average number of nutrition teaching hours in American medical schools is falling below recommendations by the National Academy of Sciences and nutritional education in the medical school curriculum is currently an important discussion topic. AIMS: This study aimed to review the teaching hours delivered during a 6-year medical programme at The Royal College of Surgeons in Ireland-Bahrain (RCSI-B) and define the importance of nutritional education for medical students. METHODS: Lecture time regarding the topic of nutrition was quantified by studying the contents of the 6-year course materials on the Moodle(r) platform virtual learning environment used by RCSI-B. RESULTS: Students are exposed to approximately 15 h of education in nutrition during their medical studies at RCSI-B. CONCLUSIONS: The 15 h spent educating RCSI-B medical students on nutrition is inadequate according to international recommendations. However, RCSI-B is one of many medical schools that do not reach the minimum required hours (25-44) as set by the National Academy of Sciences and the American Society for Nutrition. We recommend that more teaching hours on nutrition be introduced into the curriculum. These extra teaching hours may greatly benefit RCSI-B students, patients and public health in Bahrain. PMID- 26563110 TI - Flowing atmospheric pressure afterglow combined with laser ablation for direct analysis of compounds separated by thin-layer chromatography. AB - A thin-layer chromatography-mass spectrometry (TLC-MS) setup for characterization of low molecular weight compounds separated on standard TLC plates has been constructed. This new approach successfully combines TLC separation, laser ablation, and ionization using flowing atmospheric pressure afterglow (FAPA) source. For the laser ablation, a low-priced 445-nm continuous-wave diode laser pointer, with a power of 1 W, was used. The combination of the simple, low-budget laser pointer and the FAPA ion source has made this experimental arrangement broadly available, also for small laboratories. The approach was successfully applied for the characterization of low molecular weight compounds separated on TLC plates, such as a mixture of pyrazole derivatives, alkaloids (nicotine and sparteine), and an extract from a drug tablet consisting of paracetamol, propyphenazone, and caffeine. The laser pointer used was capable of ablating organic compounds without the need of application of any additional substances (matrices, staining, etc.) on the TLC spots. The detection limit of the proposed method was estimated to be 35 ng/cm(2) of a pyrazole derivative. PMID- 26563111 TI - Development and validation of an HPLC-MS method for the simultaneous quantification of key oxysterols, endocannabinoids, and ceramides: variations in metabolic syndrome. AB - Oxysterols, ceramides, and endocannabinoids are three families of bioactive lipids suggested to be involved in obesity and metabolic syndrome. To facilitate the quantification of these potentially interconnected lipids, we have developed and validated a liquid chromatography coupled to mass spectrometry method allowing for their simultaneous quantification from tissues. Sample purification is of great importance when quantifying oxysterols due to the potential artifactual conversion of cholesterol into oxysterols. Therefore, we developed a novel solid-phase extraction procedure and demonstrated that it allowed for good recoveries of the three families of analytes without artifactual oxidation of cholesterol. The oxysterols, ceramides, and endocannabinoids and their respective internal standards were chromatographically separated by HPLC and ionized using the atmospheric pressure chemical ionization (APCI) source of an LTQ-orbitrap mass spectrometer. The repeatability and bias were within the acceptance limits for all 23 lipids of interest. The sensitivity (limit of detection (LOD) and limit of quantification (LOQ)) and specificity of the method allowed us to quantify all the analytes in the liver and adipose tissue of control and high-fat diet-fed C57BL/6 mice. We found that 16 weeks of high-fat diet strongly impacted the hepatic levels of several oxysterols, ceramides, and endocannabinoids. A partial least-squares discriminant analysis (PLS-DA) based on the variations of the hepatic levels of these 23 bioactive lipids allowed differentiating the lean mice from the obese mice. PMID- 26563112 TI - Isothermal solid-phase amplification system for detection of Yersinia pestis. AB - DNA amplification is required for most molecular diagnostic applications, but conventional polymerase chain reaction (PCR) has disadvantages for field testing. Isothermal amplification techniques are being developed to respond to this problem. One of them is the recombinase polymerase amplification (RPA) that operates at isothermal conditions without sacrificing specificity and sensitivity in easy-to-use formats. In this work, RPA was used for the optical detection of solid-phase amplification of the potential biowarfare agent Yersinia pestis. Thiolated forward primers were immobilized on the surface of maleimide-activated microtitre plates for the quantitative detection of synthetic and genomic DNA, with elongation occurring only in the presence of the specific template DNA and solution phase reverse primers. Quantitative detection was achieved via the use of biotinylated reverse primers and post-amplification addition of streptavidin HRP conjugate. The overall time of amplification and detection was less than 1 h at a constant temperature of 37 degrees C. Single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) sequences were detected, achieving detection limits of 4.04*10(-13) and 3.14*10(-16) M, respectively. The system demonstrated high specificity with negligible responses to non-specific targets. PMID- 26563113 TI - Retention modelling in hydrophilic interaction chromatography. AB - The retention behaviour of acidic, basic and quaternary ammonium salts and polar neutral analytes has been evaluated on acidic, basic and neutral hydrophilic interaction chromatography (HILIC) stationary phases as a function of HILIC operating parameters such as MeCN content, buffer concentration, pH and temperature. Numerous empirical HILIC retention models (existing and newly developed ones) have been assessed for their ability to describe retention as a function of the HILIC operating parameters investigated. Retention models have been incorporated into a commercially available retention modelling programme (i.e. ACD/LC simulator) and their accuracy of retention prediction assessed. The applicability of HILIC modelling using these equations has been demonstrated in the two-dimensional isocratic (i.e. buffer concentration versus MeCN content modelling) and one-dimensional gradient separations for a range of analytes of differing physico-chemical properties on the three stationary phases. The accuracy of retention and peak width prediction was observed to be comparable to that reported in reversed-phase chromatography (RPC) retention modelling. Intriguingly, our results have confirmed that the use of gradient modelling to predict HILIC isocratic conditions and vice versa is not reliable. A relative ranking of the importance of the retention and selectivity of HILIC operating parameters has been determined using statistical approaches. For retention, the order of importance was observed to be organic content > stationary phase > temperature ~ mobile phase pH (i.e. pH 3-6 which mainly effects the ionization of the analyte) ~ buffer concentration. For selectivity, the nature of the stationary phase > mobile phase pH > buffer concentration > temperature > organic content. PMID- 26563114 TI - Continuous renal replacement therapy in children: fluid overload does not always predict mortality. AB - BACKGROUND: Mortality among critically ill children requiring continuous renal replacement therapy (CRRT) is high. Several factors have been identified as outcome predictors. Many studies have specifically reported a positive association between the fluid overload at CRRT initiation and the mortality of critically ill pediatric patients. METHODS: This study is a retrospective single center analysis including all patients admitted to the pediatric intensive care unit (PICU) of our hospital who received CRRT between 2000 and 2012. One hundred thirty-one patients were identified and subsequently classified according to primary disease. Survival rates, severity of illness and fluid balance differed among subgroups. The primary outcome was patient survival to PICU discharge. RESULTS: Overall survival to PICU discharge was 45.8 %. Based on multiple regression analysis, mortality was independently associated with onco hematological disease [odds ratio (OR) 11.7, 95 % confidence interval (CI) 1.3 104.7; p = 0.028], severe multiple organ dysfunction syndrome (MODS) (OR 5.1, 95 % CI 1.7-15; p = 0.003) and hypotension (OR 11.6, 95 % CI 1.4-93.2; p = 0.021). In the subgroup analysis, a fluid overload (FO) of more than 10 % (FO>10 %) at the beginning of CRRT seems to be a negative predictor of mortality (OR 10.9, 95 % CI 0.78-152.62; p = 0.07) only in children with milder disease (renal patients). Due to lack of statistical power, the independent effect of fluid overload on mortality could not be analyzed in all subgroups of patients. CONCLUSIONS: In children treated with CRRT the underlying diagnosis and severity of illness are independent risk factors for mortality. The degree of FO is a negative predictor only in patients with milder disease. PMID- 26563115 TI - Anti-interleukin 1 treatment in secondary amyloidosis associated with autoinflammatory diseases. AB - BACKGROUND: Amyloidosis may complicate autoinflammatory diseases (AID). We aimed to evaluate the renal biopsy findings, and clinical and laboratory parameters in patients with AID-associated amyloidosis who have responded to anti-interleukin 1(IL1) treatment. METHODS: Two children with systemic juvenile idiopathic arthritis and one with cryopyrin-associated periodic syndrome diagnosed as having reactive amyloidosis were treated with anti-IL1 drugs. The renal histopathological findings at the time of diagnosis of amyloidosis and after the onset of anti-IL1 were evaluated according to the amyloid scoring/grading system. RESULTS: The median age of disease onset and diagnosis of amyloidosis were 3 and 12 years, respectively. Anakinra was started in all; however, anakinra caused a local cutaneous reaction in one, thus canakinumab was commenced. Proteinuria improved in all. Control renal biopsies were performed a median of 3 years after the first biopsies. The renal amyloid prognostic score did not improve in patient 1, and progressed in patients 2 and 3. The renal amyloid grade progressed in patient 2. CONCLUSIONS: This is the first series demonstrating progression of renal tissue damage after the improvement of proteinuria with anti-IL 1 in AID associated amyloidosis. Anti-IL1 drugs are important to prevent further amyloid accumulation; however, new treatment strategies are needed to target the amyloid deposits. PMID- 26563116 TI - Sevelamer crystals in the mucosa of the gastrointestinal tract in a teenager with end-stage renal disease. AB - BACKGROUND: Non-calcium-containing phosphate binders, such as sevelamer preparations, are being increasingly used in patients on dialysis due to their lower association with hypercalcemia and cardiovascular morbidity and mortality. While minor gastrointestinal side effects are quite common with the use of sevelamer, more serious gastrointestinal toxicities have only rarely been reported. CASE-DIAGNOSIS/TREATMENT: We report a pediatric patient on maintenance dialysis receiving sevelamer hydrochloride who developed severe abdominal pain and a high-grade stricture of the sigmoid colon. The patient underwent exploratory laparotomy, resulting in a partial colectomy and colostomy. Histopathologic examination showed colonic mucosal injury and characteristic "fish-scale"-like sevelamer hydrochloride crystals within the mucosa. CONCLUSIONS: Whether the sevelamer crystals were causal, contributory or purely incidental remains to be clearly elucidated. However, our case raises sufficient concern to warrant additional investigation into whether there is a causal relationship between sevelamer use and intestinal mucosal injury. PMID- 26563117 TI - Acute L-arginine supplementation has no effect on cardiovascular or thermoregulatory responses to rest, exercise, and recovery in the heat. AB - PURPOSE: To investigate the effect of acute L-arginine (L-ARG) supplementation on cardiovascular and thermoregulatory responses to rest, exercise, and recovery in the heat. METHODS: Eight healthy men (age 27 +/- 6 years; stature 176 +/- 6 cm; body mass 76 +/- 4 kg; maximal power output 237 +/- 39 W) participated in a double-blind, crossover study, attending the laboratory for two experimental trials. On each occasion, participants consumed 500 ml of a black currant flavoured cordial beverage 30 min before completing a 90 min experiment in the heat (35 degrees C and 50% rh). The experiment consisted of 30 min of seated rest, followed by 30 min submaximal cycling (60% maximal power output) and 30 min passive seated recovery. On one visit the drink contained 10 g of dissolved L-ARG while on the other visit it did not. RESULTS: L-ARG supplementation increased plasma L-ARG concentrations (peak +223 +/- 80% after 60 min of the 90 min experiment); however, supplementation had no effect on rectal temperature, mean skin temperature, heart rate, arterial pressure, forearm skin vascular conductance, oxygen consumption or sweat loss at rest, during exercise, or during recovery in the heat (p > 0.05). CONCLUSION: Acute ingestion of 10 g L-ARG supplementation failed to elicit any changes in the cardiovascular or thermoregulatory responses to active or passive heat exposure in young, healthy males. PMID- 26563118 TI - Accuracy and usefulness of noninvasive fractional flow reserve from computed tomographic coronary angiography: comparison with myocardial perfusion imaging, echocardiographic coronary flow reserve, and invasive fractional flow reserve. AB - We present a case of coronary artery disease with intermediate stenosis in the proximal left anterior descending artery, which was evaluated using multiple functional modalities. FFRCT demonstrated a significant perfusion abnormality in the LAD, and the value of FFRCT (0.68) was similar to the value measured by invasive FFR (0.67). However, the other modalities gave discrepant results. In particular, perfusion scintigraphy with thallium showed no evidence of an inducible perfusion abnormality in the LAD territory. The patient was treated by PCI for two tandem lesions in the LAD. FFRCT may have potential as a default noninvasive method for assessment of coronary anatomy and physiology. PMID- 26563119 TI - Intrathecal Ziconotide and Morphine for Pain Relief: A Case Series of Eight Patients with Refractory Cancer Pain, Including Five Cases of Neuropathic Pain. AB - INTRODUCTION: Studies have shown that, at low doses and with careful titration, combination therapy with intrathecal ziconotide and morphine results in rapid control of opioid-refractory cancer pain. However, there is a lack of published data regarding the efficacy and safety of intrathecal ziconotide specifically for the treatment of neuropathic cancer pain. CASE SERIES: Case reports of ziconotide intrathecal infusion in eight patients (age 45-71 years; 75% male) with chronic, uncontrolled cancer pain during therapy with intrathecal morphine plus bupivacaine were reviewed. Neuropathic pain was confirmed in five patients. Treatment was initiated with adjunctive ziconotide when pain >=5 on a visual analog scale persisted in spite of 3 successive 20% dose increases of intrathecal morphine. Ziconotide was initiated at 0.5-1.0 ug/day, with mean increases of 0.5 ug every 4-7 days if required (maximum dose 10 ug/day; mean dose 4.9 ug/day). Pain intensity was reduced in all patients after 3-5 days. Of the eight patients, three died for reasons unrelated to ziconotide, three discontinued treatment due to adverse effects (predominantly psychoneurological disorders), and one patient is still receiving treatment. One patient discontinued ziconotide due to confusion and delirium. Due to continued lack of pain control with intrathecal morphine, intrathecal fentanyl was initiated; however, effective pain relief was not achieved with 1500 ug/day. Ziconotide was restarted and the patient then achieved pain control. CONCLUSION: On the basis of our clinical experience, we recommend adding ziconotide to intrathecal opioid-based therapy in cancer patients with neuropathic pain inadequately controlled by intrathecal morphine alone. FUNDING: Eisai, Spain. PMID- 26563121 TI - Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score. AB - PURPOSE: To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. METHODS: We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT. RESULTS: PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of <=1, 1-2 and >=2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA >=2 ng/ml, 19 (95%) had a positive scan and 12 (60%) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36%) had a positive scan and 1 (7%) had M1a disease. CONCLUSION: [(68)Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [(68)Ga]PSMA HBED-CC PET/CT. PMID- 26563122 TI - Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. AB - PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings. PMID- 26563124 TI - Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes. AB - Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE. PMID- 26563125 TI - Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis. AB - As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 +/- 3.6 and 17.8 +/- 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 +/- 2.6 and 17.3 +/- 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 +/ 6.9 and 12.7 +/- 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 +/- 1.9 and 26.2 +/- 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE. PMID- 26563126 TI - Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders. AB - Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD SUD comorbidity, PRKCI deserves further investigation in BD-AUD. PMID- 26563127 TI - Chemically induced acute model of sarcosinemia in wistar rats. AB - In the present study, we developed an acute chemically induced model of sarcosinemia in Wistar rats. Wistar rats of 7, 14 and 21 postpartum days received sarcosine intraperitoneally in doses of 0.5 mmol/Kg of body weight three time a day at intervals of 3 h. Control animals received saline solution (NaCl 0.85 g%) in the same volume (10 mL/Kg of body weight). The animals were killed after 30 min, 1, 2, 3 or 6 h after the last injection and the brain and the blood were collected for sarcosine measurement. The results showed that plasma and brain sarcosine concentrations achieved levels three to four times higher than the normal levels and decreased in a time-dependent way, achieving normal levels after 6 hours. Considering that experimental animal models are useful to investigate the pathophysiology of human disorders, our model of sarcosinemia may be useful for the research of the mechanisms of neurological dysfunction caused by high tissue sarcosine levels. PMID- 26563129 TI - Antibiotic prescribing is higher in deprived areas of England. PMID- 26563128 TI - A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. AB - PURPOSE: This trial was conducted to determine the maximum tolerated dose (MTD) and preliminary efficacy of buparlisib, an oral pan-class I PI3K inhibitor, plus fulvestrant in postmenopausal women with metastatic estrogen receptor positive (ER(+)) breast cancer. EXPERIMENTAL DESIGN: Phase IA employed a 3+3 design to determine the MTD of buparlisib daily plus fulvestrant. Subsequent cohorts (phase IB and cohort C) evaluated intermittent (5/7-day) and continuous dosing of buparlisib (100 mg daily). No more than 3 prior systemic treatments in the metastatic setting were allowed in these subsequent cohorts. RESULTS: Thirty-one patients were enrolled. MTD was defined as buparlisib 100 mg daily plus fulvestrant. Common adverse events (AE) included fatigue (38.7%), transaminases elevation (35.5%), rash (29%), and diarrhea (19.4%). C-peptide was significantly increased during treatment, consistent with on-target effect of buparlisib. Compared with intermittent dosing, daily buparlisib was associated with more frequent early onset AEs and higher buparlisib plasma concentrations. Among the 29 evaluable patients, the clinical benefit rate was 58.6% (95% CI, 40.7%-74.5%). Response was not associated with PIK3CA mutation or treatment cohort; however, loss of PTEN, progesterone receptor (PgR) expression, or mutation in TP53 was most common in resistant cases, and mutations inAKT1 and ESR1 did not exclude treatment response. CONCLUSIONS: Buparlisib plus fulvestrant is clinically active with manageable AEs in patients with metastatic ER(+)breast cancer. Weekend breaks in buparlisib dosing reduced toxicity. Patients with PgR negative and TP53 mutation did poorly, suggesting buparlisib plus fulvestrant may not be adequately effective against tumors with these poor prognostic molecular features. PMID- 26563130 TI - Evaluating the appropriateness of a community pharmacy model for a colorectal cancer screening program in Catalonia (Spain). AB - Background The traditional model of community pharmacy has changed, with patients, caregivers and consumers having access to many cognitive services other than the traditional dispensing and supply of medicines. In December 2009, a population-based colorectal cancer screening program started in Barcelona, introducing the community pharmacist and the professional expertise of the pharmacist into the organisational model. Aim To evaluate the program implementation process in the pharmacies, identify barriers and facilitators, and know the opinion of the professionals involved in the colorectal cancer screening program in Catalonia (Spain). Methods Cross-sectional study of the pharmacies that participated in the first round of the program during the first and second trimester of 2010 in Barcelona. A validated questionnaire was used to analyse several functional aspects in the implementation process. Qualitative aspects about the opinion of the pharmacist were studied. A descriptive and bivariate analysis was performed. Results All the pharmacies involved in the program (n = 74) participated in the study. The majority of the sample population was composed of women (70.3%), mean age 44.9 years, and most of them (74%) had attended a specific training session. Pharmacists considered their participation in the program to be an added value to their professional role and a way to increase consumer's confidence on this kind of services. The average time to provide the service was estimated to be less than 10 minutes per consumer. Only three (4.1%) pharmacists considered that the program involved a lot of extra work in the daily activities of the pharmacy. The level of satisfaction of the pharmacists was very high. Conclusions Community pharmacies can be a successful alternative and great resource to implement a population cancer screening program. This functional model can improve the accessibility and participation rates on target population. The level of motivation of the community pharmacist, the specific training program and the perception to give a better care for their patients can be an enabler. PMID- 26563131 TI - Adapting to a Changing Environment: Modeling the Interaction of Directional Selection and Plasticity. AB - Human-induced habitat loss and fragmentation constrains the range of many species, making them unable to respond to climate change by moving. For such species to avoid extinction, they must respond with some combination of phenotypic plasticity and genetic adaptation. Haldane's "cost of natural selection" limits the rate of adaptation, but, although modeling has shown that in very large populations long-term adaptation can be maintained at rates substantially faster than Haldane's suggested limit, maintaining large populations is often an impossibility, so phenotypic plasticity may be crucial in enhancing the long-term survival of small populations. The potential importance of plasticity is in "buying time" for populations subject to directional environmental change: if genotypes can encompass a greater environmental range, then populations can maintain high fitness for a longer period of time. Alternatively, plasticity could be detrimental by lessening the effectiveness of natural selection in promoting genetic adaptation. Here, I modeled a directionally changing environment in which a genotype's adaptive phenotypic plasticity is centered around the environment where its fitness is highest. Plasticity broadens environmental tolerance and, provided it is not too costly, is favored by natural selection. However, a paradoxical result of the individually advantageous spread of plasticity is that, unless the adaptive trait is determined by very few loci, the long-term extinction risk of a population increases. This effect reflects a conflict between the short-term individual benefit of plasticity and a long-term detriment to population persistence, adding to the multiple threats facing small populations under conditions of climate change. PMID- 26563132 TI - ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells. AB - TP53 and ataxia telangiectasia mutated (ATM) defects are associated with genomic instability, clonal evolution, and chemoresistance in chronic lymphocytic leukemia (CLL). Currently, therapies capable of providing durable remissions in relapsed/refractory TP53- or ATM-defective CLL are lacking. Ataxia telangiectasia and Rad3-related (ATR) mediates response to replication stress, the absence of which leads to collapse of stalled replication forks into chromatid fragments that require resolution through the ATM/p53 pathway. Here, using AZD6738, a novel ATR kinase inhibitor, we investigated ATR inhibition as a synthetically lethal strategy to target CLL cells with TP53 or ATM defects. Irrespective of TP53 or ATM status, induction of CLL cell proliferation upregulated ATR protein, which then became activated in response to replication stress. In TP53- or ATM defective CLL cells, inhibition of ATR signaling by AZD6738 led to an accumulation of unrepaired DNA damage, which was carried through into mitosis because of defective cell cycle checkpoints, resulting in cell death by mitotic catastrophe. Consequently, AZD6738 was selectively cytotoxic to both TP53- and ATM-defective CLL cell lines and primary cells. This was confirmed in vivo using primary xenograft models of TP53- or ATM-defective CLL, where treatment with AZD6738 resulted in decreased tumor load and reduction in the proportion of CLL cells with such defects. Moreover, AZD6738 sensitized TP53- or ATM-defective primary CLL cells to chemotherapy and ibrutinib. Our findings suggest that ATR is a promising therapeutic target for TP53- or ATM-defective CLL that warrants clinical investigation. PMID- 26563120 TI - Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. AB - Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information. PMID- 26563134 TI - Evidence for two-dimensional Ising superconductivity in gated MoS2. AB - The Zeeman effect, which is usually detrimental to superconductivity, can be strongly protective when an effective Zeeman field from intrinsic spin-orbit coupling locks the spins of Cooper pairs in a direction orthogonal to an external magnetic field. We performed magnetotransport experiments with ionic-gated molybdenum disulfide transistors, in which gating prepared individual superconducting states with different carrier dopings, and measured an in-plane critical field B(c2) far beyond the Pauli paramagnetic limit, consistent with Zeeman-protected superconductivity. The gating-enhanced B(c2) is more than an order of magnitude larger than it is in the bulk superconducting phases, where the effective Zeeman field is weakened by interlayer coupling. Our study provides experimental evidence of an Ising superconductor, in which spins of the pairing electrons are strongly pinned by an effective Zeeman field. PMID- 26563133 TI - Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect. AB - We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 * 10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P = .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD. PMID- 26563135 TI - Fast retreat of Zachariae Isstrom, northeast Greenland. AB - After 8 years of decay of its ice shelf, Zachariae Isstrom, a major glacier of northeast Greenland that holds a 0.5-meter sea-level rise equivalent, entered a phase of accelerated retreat in fall 2012. The acceleration rate of its ice velocity tripled, melting of its residual ice shelf and thinning of its grounded portion doubled, and calving is now occurring at its grounding line. Warmer air and ocean temperatures have caused the glacier to detach from a stabilizing sill and retreat rapidly along a downward-sloping, marine-based bed. Its equal-ice volume neighbor, Nioghalvfjerdsfjorden, is also melting rapidly but retreating slowly along an upward-sloping bed. The destabilization of this marine-based sector will increase sea-level rise from the Greenland Ice Sheet for decades to come. PMID- 26563136 TI - Low back pain and physical activity--A 6.5 year follow-up among young adults in their transition from school to working life. AB - BACKGROUND: The association between leisure time physical activity and low back pain in young adults is unclear and is in the need of prospectively obtained evidence. This study examined the course of low back pain and the association between low back pain and leisure time physical activity in a cohort of young adults in their transition from school to working life. METHODS: Both low back pain and leisure time physical activity was monitored over a 6.5 year period in 420 subjects starting out as students within hairdressing, electrical installation and media/design. The association between physical activity and low back pain was investigated through the follow-up period by using linear mixed models analysis. RESULTS: Low back pain was significantly influenced by time and overall there was a decreasing trend of low back pain prevalence throughout the follow-up. Analysis showed a weak trend of decreasing low back pain with moderate/high physical activity levels, but this association was not significant. CONCLUSIONS: Low back pain decreased during follow-up with baseline as reference. Findings in our study did show non-significant trends of reduced low back pain with increased leisure time physical activity. Still, we could not support the theory of moderate/high levels of physical activity acting protective against low back pain in young adults entering working life. Our results, in combination with previous relevant research, cannot support a clear relationship between physical activity and low back pain for young adults. Thus, recommendations regarding effect of physical activity on reducing low back pain for this group are not clear. PMID- 26563137 TI - Visual impairment, coping strategies and impact on daily life: a qualitative study among working-age UK ex-service personnel. AB - BACKGROUND: Sustaining a visual impairment may have a substantial impact on various life domains such as work, interpersonal relations, mobility and social and mental well-being. How to adjust to the loss of vision and its consequences might be a challenge for the visually impaired person. The purpose of the current study was to explore how younger male ex-Service personnel cope with becoming visually impaired and how this affects their daily life. METHODS: Semi-structured interviews with 30 visually impaired male ex-Service personnel, all under the age of 55, were conducted. All participants are members of the charity organisation Blind Veterans UK. Interviews were analysed thematically. RESULTS: Younger ex Service personnel applied a number of different strategies to overcome their loss of vision and its associated consequences. Coping strategies varied from learning new skills, goal setting, integrating the use of low vision aids in their daily routine, to social withdrawal and substance misuse. Vision loss affected on all aspects of daily life and ex-Service personnel experienced an on-going struggle to accept and adjust to becoming visually impaired. CONCLUSIONS: Health care professionals, family and friends of the person with the visual impairment need to be aware that coping with a visual impairment is a continuous struggle; even after a considerable amount of time has passed, needs for emotional, social, practical and physical support may still be present. PMID- 26563138 TI - Decomposing contribution of age and non-age factors to rapid growth of lung cancer in Xuanwei over past 30 years. AB - BACKGROUND: From 1973 to 2005, the lung cancer mortality in Xuanwei had increased constantly. Effect analysis of age and non-age factors on lung cancer is important for local policy-making. METHODS: Demographic and death data was collected and used. Factors of lung cancer were classified into age and non-age factors. The contribution of the two factors to lung cancer was evaluated by method of decomposing the differences of mortality rate. RESULTS: For males, the non-age factors were the major contributor to growth of lung cancer mortality, and 78.46% of all growth was attributed to non-age factors. For females, the non age factors were the absolute contributor to growth of lung cancer in 1973-1992. From 1992 to 2005, the contribution proportion had reduced to 75.39%. CONCLUSIONS: Aging was one of risk factors for lung cancer in Xuanwei, but not the main factor. It was supposed that multiple environmental risk factors were related with high growth of lung cancer in Xuanwei. Policy-making should focus on the non-age factors. PMID- 26563139 TI - Non-criteria anti-phospholipid antibodies and cognitive impairment in SLE. AB - The pathogenesis of cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) is unknown. Anti-phospholipid antibodies (APL) have been implicated. The APL which have been evaluated have variably included anti cardiolipin (ACL) antibodies, lupus anticoagulant (LAC), and antibodies to beta-2 glycoprotein I (beta2GPI). Few studies have examined other APL (so-called non criteria APL). We evaluated the association of CI with a broad spectrum of non criteria APL. Subjects meeting SLE classification criteria were recruited from three different patient populations. Cognitive function was assessed with the Automated Neuropsychologic Assessment Metrics (ANAM), a validated computer-based assessment tool. The total throughput score (TTS = number of correct responses/time) was used as the primary outcome measure. The following APL of all three isotypes were assessed by ELISA using standardized techniques: anti beta2GPI, anti-phosphatidyl ethanolamine (aPE), anti-phosphatidyl choline (aPC), anti-phosphatidyl inositol (aPI), anti-phosphatidyl serine (aPS), anti phosphatidyl glycerol (aPG), anti-phosphatidic acid (aPA). Fifty-seven (57) patients were evaluated. Of the 57, 12 had definite CI (>1.5 SD below the mean of an age-, sex-, and race-matched RA population). The two groups were significantly different with regard to age, ethnicity, and family income. There was no significant difference between groups with regard to the presence of any non criteria APL. When titers of specific non-criteria APL were compared with TTS, no significant correlations were found. Using multiple linear regression and adjusting for relevant covariates including age, ethnicity, and family income, neither the presence nor the titer of any non-criteria APL significantly influenced TTS. In this cross-sectional study, non-criteria APL were not associated with CI. PMID- 26563140 TI - Harmony as Ideology: Questioning the Diversity-Stability Hypothesis. AB - The representation of a complex but stable, self-regulated and, finally, harmonious nature penetrates the whole history of Ecology, thus contradicting the core of the Darwinian evolution. Originated in the pre-Darwinian Natural History, this representation defined theoretically the various schools of early ecology and, in the context of the cybernetic synthesis of the 1950s, it assumed a typical mathematical form on account of alpha positive correlation between species diversity and community stability. After 1960, these two aforementioned concepts and their positive correlation were proposed as environmental management tools, in the face of the ecological crisis arising at the time. In the early 1970s, and particularly after May's evolutionary arguments, the consensus around this positive correlation collapsed for a while, only to be promptly restored for the purpose of attaching an ecological value on biodiversity. In this paper, we explore the history of the diversity-stability hypothesis and we review the successive terms that have been used to express community stability. We argue that this hypothesis has been motivated by the nodal ideological presuppositions of order and harmony and that the scientific developments in this field largely correspond to external social pressures. We conclude that the conflict about the diversity-stability relationship is in fact an ideological debate, referring mostly to the way we see nature and society rather than to an autonomous scientific question. From this point of view, we may understand why Ecology's concepts and perceptions may decline and return again and again, forming a pluralistic scientific history. PMID- 26563141 TI - About the usefulness of contact precautions for carriers of extended-spectrum beta-lactamase-producing Escherichia coli. AB - BACKGROUND: Extended-spectrum beta-lactamases producing Escherichia coli (ESBL-E) are increasingly identified in health care facilities. As previously done for the control of methicillin-resistant Staphylococcus aureus, many hospitals have established screening strategies for early identification of patients being carriers of ESBL producers in general and ESBL-E in particular, and have implemented contact precautions (CP) for infected and colonized patients. METHODS: The incidence of ESBL-E has been compared retrospectively between two French university hospitals (A and B) with different infection control policies over a 5-year long period of time (2006-2010). RESULTS: While hospital A only implemented standard precautions after identification of patients colonized with ESBL-E, hospital B recommended additional CP. During the period of the study, the ESBL-E incidence rate significantly increased in both hospitals, but no significant difference was observed between the two hospitals. CONCLUSIONS: This observational study did not reveal that additional CP measures had a greater impact on the incidence of ESBL-E in hospital settings. PMID- 26563142 TI - Anti-miroestrol polyclonal antibodies: a comparison of immunogen preparations used to obtain desired antibody properties. AB - Immunogen quality is one important factor that contributes to desirable antibody characteristics. Highly specific antibodies against miroestrol can be used to develop a quality control immunoassay for Pueraria candollei products. In this study, we investigated how various immunogen preparations affect antibody properties. The results show that immunogen prepared using the Mannich reaction provides antibodies with higher specificity and sensitivity against miroestrol than immunogen prepared with the periodate reaction. The results suggest the Mannich reaction maintains the original structure of miroestrol and generates useful antibodies for developing immunoassays. PMID- 26563143 TI - X-rays for diagnosis of craniosynostosis. PMID- 26563144 TI - [Pseudo-radicular referred leg pain]. AB - Pseudo-radicular leg pain as initially described by Bruegger more than 55 years ago was at that time a genius explanation for so many non-radicular pain syndromes that needed not any kind of surgical intervention but in first line a manual treatment or a treatment by therapeutic local anesthetics. Today we describe this pain as a "referred pain" originating from other anatomic structures that may occur during the development of chronic pain. Nevertheless this pain is found in many patients and it still seems to be a big problem for many physicians and surgeons. Imaging does not help either. The history and the clinical symptoms, the examinations, the chain reactions in the motor system as well as the treatment options from the point of view of manual medicine are described. PMID- 26563145 TI - SATB1 is a potential therapeutic target in intrahepatic cholangiocarcinoma. AB - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor of the liver with a poor prognosis. Upregulation of special AT-rich sequence-binding protein 1 (SATB1) promotes tumor progression. However, little is known about the role of SATB1 in ICC tumorigenesis. METHODS: We firstly investigated the expression of SATB1 in 88 cases of ICC by immunohistochemistry (IHC), QRT-PCR, and western blot. Meanwhile, we constructed stably knockdown (shRNA) of SATB1 in ICC cell lines to evaluate the effects of SATB1 on the ability of cell proliferation and invasion by MTT and transwell invasion assay. RESULTS: Our result showed that SATB1 was overexpressed in ICC tissues samples. Knockdown of SATB1 could inhibit ICC cell proliferation, and suppress ICC cell invasion of ICC cell lines. In addition, the depletion of SATB1 expression suppressed the MYC levels in vitro. CONCLUSIONS: Our results highlight the significance of SATB1 in ICC and suggest that SATB1 could be a promising therapy target and a potential biomarker for prognosis in ICC patients. PMID- 26563146 TI - Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer. AB - PURPOSE: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-kappaB and STAT3 signaling pathways. To better understand the correlation of NF-kappaB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. RESULTS: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. CONCLUSIONS: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients' prognosis of PCa, implying their potentials as candidate markers of this cancer. PMID- 26563147 TI - A pilot study to improve adherence among MS patients who discontinue treatment against medical advice. AB - Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690. PMID- 26563148 TI - Effects of a mindfulness-based intervention on mindful eating, sweets consumption, and fasting glucose levels in obese adults: data from the SHINE randomized controlled trial. AB - We evaluated changes in mindful eating as a potential mechanism underlying the effects of a mindfulness-based intervention for weight loss on eating of sweet foods and fasting glucose levels. We randomized 194 obese individuals (M age = 47.0 +/- 12.7 years; BMI = 35.5 +/- 3.6; 78% women) to a 5.5-month diet-exercise program with or without mindfulness training. The mindfulness group, relative to the active control group, evidenced increases in mindful eating and maintenance of fasting glucose from baseline to 12-month assessment. Increases in mindful eating were associated with decreased eating of sweets and fasting glucose levels among mindfulness group participants, but this association was not statistically significant among active control group participants. Twelve-month increases in mindful eating partially mediated the effect of intervention arm on changes in fasting glucose levels from baseline to 12-month assessment. Increases in mindful eating may contribute to the effects of mindfulness-based weight loss interventions on eating of sweets and fasting glucose levels. PMID- 26563150 TI - Cathepsin D inhibitors as potential therapeutics for breast cancer treatment: Molecular docking and bioevaluation against triple-negative and triple-positive breast cancers. AB - The main aim of this study was to discover small molecule inhibitors against Cathepsin D (CatD) (EC.3.4.23.5), a clinically proven prognostic marker for breast cancer, and to explore the mechanisms by which CatD could be a useful therapeutic target for triple-positive and triple-negative breast cancers (TPBC & TNBC). The crystal structure of CatD at 2.5 A resolution (PDB: 1LYB), which was complexed with Pepstatin A, was selected for computer-aided molecular modeling. The methods used in our study were pharmacophore modeling and molecular docking. Virtual screening was performed to identify small molecules from an in-house database and a large commercial chemical library. Cytotoxicity studies were performed on human normal cell line HEK293T and growth inhibition studies on breast adenocarcinoma cell lines, namely MCF-7, MDA-MB-231, SK-BR-3, and MDA-MB 468. Furthermore, RT-PCR analysis, in vitro enzyme assay, and cell cycle analysis ascertained the validity of the selected molecules. A set of 28 molecules was subjected to an in vitro fluorescence-based inhibitory activity assay, and among them six molecules exhibited >50 % inhibition at 25MUM. These molecules also exhibited good growth inhibition against TPBC and TNBC cancer types. Among them, molecules 1 and 17 showed single-digit micromolar GI50 values against MCF-7 and MDA-MB-231 cell lines. PMID- 26563149 TI - Overexpression of AtPCS1 in tobacco increases arsenic and arsenic plus cadmium accumulation and detoxification. AB - MAIN CONCLUSION: The heterologous expression of AtPCS1 in tobacco plants exposed to arsenic plus cadmium enhances phytochelatin levels, root As/Cd accumulation and pollutants detoxification, but does not prevent root cyto-histological damages. High phytochelatin (PC) levels may be involved in accumulation and detoxification of both cadmium (Cd) and arsenic (As) in numerous plants. Although polluted environments are frequently characterized by As and Cd coexistence, how increased PC levels affect the adaptation of the entire plant and the response of its cells/tissues to a combined contamination by As and Cd needs investigation. Consequently, we analyzed tobacco seedlings overexpressing Arabidopsis phytochelatin synthase1 gene (AtPCS1) exposed to As and/or Cd, to evaluate the levels of PCs and As/Cd, the cyto-histological modifications of the roots and the Cd/As leaf extrusion ability. When exposed to As and/or Cd the plants overexpressing AtPCS1 showed higher PC levels, As plus Cd root accumulation, and detoxification ability than the non-overexpressing plants, but a blocked Cd extrusion from the leaf trichomes. In all genotypes, As, and Cd in particular, damaged lateral root apices, enhancing cell-vacuolization, causing thinning and stretching of endodermis initial cells. Alterations also occurred in the primary structure region of the lateral roots, i.e., cell wall lignification in the external cortex, cell hypertrophy in the inner cortex, crushing of endodermis and stele, and nuclear hypertrophy. Altogether, As and/or Cd caused damage to the lateral roots (and not to the primary one), with such damage not counteracted by AtPCS1 overexpression. The latter, however, positively affected accumulation and detoxification to both pollutants, highlighting that Cd/As accumulation and detoxification due to PCS1 activity do not reduce the cyto-histological damage. PMID- 26563151 TI - Genomic gain of the PRL-3 gene may represent poor prognosis of primary colorectal cancer, and associate with liver metastasis. AB - PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis. PMID- 26563152 TI - Health Resource Utilization in Patients with Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy in China. AB - BACKGROUND AND OBJECTIVES: Chemotherapy is the preferred treatment regimen for advanced lung cancer patients. This study investigated the health resources utilized by and medical expenses of patients with non-small cell lung cancer (NSCLC) as well as the influence of various chemotherapy regimens on the final medical costs in China. The aim of this study was to provide physicians with a reference to use as the basis for their choice of treatment. METHODS: Data were collected from the Shanghai Chest Hospital's medical charts and billing database. The collected patient information included the baseline characteristics, medical history, chemotherapy regimens, and medical costs, which were used to estimate the health resources utilized by patients and the cost of treatment. RESULTS: This study included 328 patients, and the average total medical cost was $US14,165. This cost included drugs, which accounted for as much as 78.91% of the total cost, and chemotherapy drugs, which accounted for 51.58% of total drug expenses. The most frequently utilized chemotherapy drug was carboplatin, and the most expensive chemotherapy drug was erlotinib. In drug combinations, gemcitabine was utilized most frequently, the combination of gemcitabine and paclitaxel was the most expensive, and cisplatin was the least expensive drug. Epidermal growth factor receptor-positive patients were treated with targeted drug therapy (icotinib, erlotinib, and gefitinib). The use of recombinant human endostatin was often combined with a vinorelbine plus cisplatin regimen. Traditional Chinese medicines were the most frequently utilized non-chemotherapy drugs, and these drugs were also the most expensive. CONCLUSIONS: The final cost significantly depended on the specific chemotherapy regimen; thus, the rationale and cost of the chemotherapy regimen and adjuvant chemotherapy should be considered in patients with advanced NSCLC. PMID- 26563153 TI - Medial and lateral hamstrings and quadriceps co-activation affects knee joint kinematics and ACL elongation: a pilot study. AB - BACKGROUND: Many injury prevention and rehabilitation programs aim to train hamstring and quadriceps co-activation to constrain excessive anterior tibial translation and protect the anterior cruciate ligament (ACL) from injury. However, despite strong clinical belief in its efficacy, primary evidence supporting training co-activation of the hamstrings and quadriceps muscles for ACL injury prevention and rehabilitation is quite limited. Therefore, the purpose of the study presented in this paper was to determine if hamstring-quadriceps co activation alters knee joint kinematics, and also establish if it affects ACL elongation. METHODS: A computed tomography (CT) scan from each participant's dominant leg was acquired prior to performing two step-ups under fluoroscopy: one with 'natural' hamstring-quadriceps co-activation, one with deliberate co activation. Electromyography was used to confirm increased motor unit recruitment. The CT scan was registered to fluoroscopy for 4-D modeling, and knee joint kinematics subsequently measured. Anterior cruciate ligament attachments were mapped to the 4-D models and its length was assumed from the distance between attachments. Anterior cruciate ligament elongation was derived from the change in distance between those points as they moved relative to each other. RESULTS: Reduced ACL elongation as well as knee joint rotation, abduction, translation, and distraction was observed for the step up with increased co activation. A relationship was shown to exist for change in ACL length with knee abduction (r = 0.91; p <= 0.001), with distraction (r = -0.70; p = 0.02 for relationship with compression), and with anterior tibial translation (r = 0.52; p = 0.01). However, ACL elongation was not associated with internal rotation or medial translation. Medial hamstring-quadriceps co-activation was associated with a shorter ACL (r = -0.71; p = 0.01), and lateral hamstring-quadriceps co activation was related to ACL elongation (r = 0.46; p = 0.05). CONCLUSION: Net co activation of the hamstrings and quadriceps muscles will likely reduce ACL elongation provided that the proportion of medial hamstring-quadriceps co activation exceeds lateral. PMID- 26563155 TI - A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection. AB - Acute aortic dissection (AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican (a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican. PMID- 26563154 TI - Genetic contribution of SCARB1 variants to lipid traits in African Blacks: a candidate gene association study. AB - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) exerts many anti atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria. METHODS: We resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits. RESULTS: The initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies <= 1%) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05). CONCLUSIONS: To our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism. PMID- 26563156 TI - Regulation of hematopoietic stem cells in the niche. AB - Hematopoiesis provides a suitable model for understanding adult stem cells and their niche. Hematopoietic stem cells (HSCs) continuously produce blood cells through orchestrated proliferation, self-renewal, and differentiation in the bone marrow (BM). Within the BM exists a highly organized microenvironment termed "niche" where stem cells reside and are maintained. HSC niche is the first evidence that a microenvironment contributes to protecting stem cell integrity and functionality in mammals. Although multiple models exist, recent progress has principally elucidated the cellular complexity of the HSC niche that maintains and regulates HSCs in BM. Here we introduce the development and summarize the achievements of HSC niche studies. PMID- 26563158 TI - An Organizational Perspective to the Creation of the Research Field. AB - The aim of the paper is to contribute to the definition and analysis of the "access to the field" (Feldman et al. 2003) through an inter-organizational perspective. The paper discusses a case study on the access of a researcher to a hospital department where both organizations and actors are shown as actively constructing the research site. Both researcher and participants are described in terms of work organizations originally engaged in parallel systems of activity. Dynamics of negotiation "tied" the different actors' activities in a new activity system where researcher and participants concur to the effectiveness of both organizations (i.e., the research and the hospital ward). An Activity Theory perspective (Leont'ev 1978) is used with the aim of focusing the analysis on the activities in charge to the different actors. The approach adopted introduces the idea that, from the outset, research is made possible by a process of co construction that works through the development of a completely new and shared work space arising around the encounter between researchers and participants. It is the balance between improvised actions and the co-creation of "boundary objects" (Star and Griesemer 1989), which makes interlacement possible between the two activity systems. The concept of "knotworking" (Engestrom 2007a) is adopted to interpret specific actions by both organizations and actors intended to build a knot of activities whereby the new research system takes place. PMID- 26563157 TI - Impaired cytoskeletal arrangements and failure of ventral body wall closure in chick embryos treated with rock inhibitor (Y-27632). AB - AIM: Rho-associated kinase (ROCK) signaling regulates numerous fundamental developmental processes during embryogenesis, primarily by controlling actin cytoskeleton assembly and cell contractility. ROCK knockout mice exhibit a ventral body wall defect (VBWD) phenotype due to disorganization of actin filaments at the umbilical ring. However, the exact molecular mechanisms leading to VBWD still remain unclear. Improper somitogenesis has been hypothesized to contribute to failure of VBW closure. We designed this study to investigate the hypothesis that administration of ROCK inhibitor (Y-27632) disrupts cytoskeletal arrangements in morphology during early chick embryogenesis, which may contribute to the development of VBWD. METHODS: At 60 h incubation, chick embryos were explanted into shell-less culture and treated with 50 uL of vehicle for controls (n = 33) or 50 uL of 500 uM of Y-27632 for the experimental group (Y-27, n = 56). At 8 h post-treatment, RT-PCR was performed to evaluate mRNA levels of N cadherin, E-cadherin and connexin43. Immunofluorescence confocal microscopy was performed to analyze the expression and distribution of actin, vinculin and microtubules in the neural tube and somites. A further cohort of embryos was treated in ovo by dropping 50 uL of vehicle or 50 uL of different concentrations of Y-27632 onto the embryo and allowing development to 12 and 14 days for further assessment. RESULTS: Gene expression levels of N-cadherin, E-cadherin and connexin43 were significantly decreased in treated embryos compared with controls (p < 0.05). Thickened actin filament bundles were recorded in the neural tube of Y-27 embryos. In somites, cells were dissociated with reduced actin distribution in affected embryos. Clumping of vinculin expression was found in the neural tube and somites, whereas reduced expression of microtubules was observed in Y-27 embryos compared with controls. At 12 and 14 days of development, affected embryos presented with an enlarged umbilical ring and herniation of abdominal contents through the defect. CONCLUSION: ROCK inhibition alters cytoskeletal arrangement during early chick embryogenesis, which may contribute to failure of anterior body wall closure causing VBWD at later stages of development. PMID- 26563159 TI - FAS Haploinsufficiency Caused by Extracellular Missense Mutations Underlying Autoimmune Lymphoproliferative Syndrome. AB - Mutations in the FAS gene are the most common cause of Autoimmune Lymphoproliferative Syndrome (ALPS), and the majority of them affect the intracellular domain of FAS protein, particularly the region termed death domain. However, approximately one third of these mutations affect the extracellular region of FAS and most are stop codons, with very few missense changes having been described to date. We previously described 7 patients with a FAS missense extracellular mutation, C107Y, two in homozygozity and 5 in heterozygosity. We investigated here the mechanistic effects of this mutation and observed that the homozygous patients did not show any FAS surface expression, while the heterozygous patients had diminished receptor expression. Aiming to understand why a missense mutation was abolishing receptor expression, we analyzed intracellular FAS protein trafficking using fluorescent fusion proteins of wild type FAS, two missense extracellular mutants (FAS-C107Y and FAS-C104Y) and one missense change localized in the intracellular region, FAS-D260E. The FAS-C107Y and FAS-C104Y mutants failed to reach the cell surface, being retained at the endoplasmic reticulum, unlike the WT or the FAS-D260E which were clearly expressed at the plasma membrane. These results support haploinsufficiency as the underlying mechanism involved in the pathogenesis of ALPS caused by extracellular FAS missense mutations. PMID- 26563160 TI - Recurrent Respiratory Infections Revealing CD8alpha Deficiency. AB - CD8A encodes the CD8alpha chain of the dimeric CD8 protein, a critical coreceptor of cytotoxic T cells. We report here the comprehensive immunological evaluation of a child with a CD8A missense mutation, providing evidence that CD8 deficiency increases susceptibility to recurrent respiratory infections without interfering with the TCR-mediated proliferation of T cells. These observations expand the known phenotypes associated with CD8 deficiency. PMID- 26563161 TI - Early Complement Component Deficiency in a Single-Centre Cohort of Pediatric Onset Lupus. AB - OBJECTIVES: To assess complement levels C1q, C2, C3 and C4 in children with pediatric-onset lupus during the quiescent stage of disease. METHODS: Thirty-four consecutive children with pediatric-onset SLE (onset below 12 years), in the quiescent stage were enrolled for the study. Twenty-nine age and sex matched healthy children were also enrolled for the purpose of comparison. Complement C1q and C2 levels were estimated by enzyme-linked immunosorbent assay (ELISA) whereas C3 and C4 were measured by end-point nephelometry. Genetic mutation analysis and functional assessment of classical complement pathway by ELISA were carried out in children with depressed levels of these complements. The study protocol was approved by the Institute Thesis Committee and the Institute Ethics Committee. RESULTS: Mean complement C1q, C2, C3 and C4 levels were 50.32, 17.28, 1320 and 236 mg/L respectively. Levels of complements were low in 7/34 children with SLE. An early age at onset, low anti-dsDNA titres and predominant skin manifestations were noted in children with decreased levels of complement C1q. Mutation analysis of C1qA gene revealed a homozygous nonsense mutation: C1QA (NM_015991) c.622C>T, p.Q208X in one child. A homozygous acceptor splice site mutation at the -2 position of intron2 of C1QA (c.164-2A>C) was detected in another child. The age at onset of disease was early in both these children, at 2.5 and 1.5 years respectively. CONCLUSION: Children with inherited deficiency of C1q and other early complement components present with early onset lupus that has a distinct clinical and immunological profile. PMID- 26563162 TI - Sleep benefits consolidation of visuo-motor adaptation learning in older adults. AB - Sleep is beneficial for performance across a range of memory tasks in young adults, but whether memories are similarly consolidated in older adults is less clear. Performance benefits have been observed following sleep in older adults for declarative learning tasks, but this benefit may be reduced for non declarative, motor skill learning tasks. To date, studies of sleep-dependent consolidation of motor learning in older adults are limited to motor sequence tasks. To examine whether reduced sleep-dependent consolidation in older adults is generalizable to other forms of motor skill learning, we examined performance changes over intervals of sleep and wake in young (n = 62) and older adults (n = 61) using a mirror-tracing task, which assesses visuo-motor adaptation learning. Participants learned the task either in the morning or in evening, and performance was assessed following a 12-h interval containing overnight sleep or daytime wake. Contrary to our prediction, both young adults and older adults exhibited sleep-dependent gains in visuo-motor adaptation. There was a correlation between performance improvement over sleep and percent of the night in non-REM stage 2 sleep. These results indicate that motor skill consolidation remains intact with increasing age although this relationship may be limited to specific forms of motor skill learning. PMID- 26563163 TI - Cerebral hemovelocity reveals differential resource allocation strategies for extraverts and introverts during vigilance. AB - Extraversion--one of the Big 5 personality factors--correlates negatively with vigilance, but most studies focus on performance outcomes and not the performance process. Previous research has shown that transcranial Doppler sonography (TCD), which measures cerebral blood flow velocity (CBFV), can be used to examine resource allocation strategies during vigilance performance. Hence, this study was designed to assess the attentional resource allocation strategies of introverts and extraverts using the CBFV measure. Twelve extroverts and 13 introverts monitored a 60-min vigilance task for a critical signal--the absence of a line on a five-circle array. The results revealed an overall performance decrement that was not modulated by extraversion. We observed an interaction between extraversion and time; CBFV declined in the introversion group, but not in the extraversion group. Additionally, an interaction between cerebral hemisphere and personality revealed that extraverts were recruiting resources from both the left and right cerebral hemispheres, while introverts only recruited resources from the right hemisphere. The results suggest that extraverts can allocate compensatory effort to mask performance differences. We discuss the theoretical and practical implications of these findings and offer future research directions that may help us understand these effects. PMID- 26563164 TI - Dissociation of the rostral and dorsolateral prefrontal cortex during sequence learning in saccades: a TMS investigation. AB - This experiment sought to find whether differences exist between the dorsolateral prefrontal cortex (DLPFC) and the medial rostral prefrontal cortex (MRPFC) for performing stimulus-independent and stimulus-oriented tasks, respectively. To find a causal relationship in these areas, we employed the use of trans-cranial magnetic stimulation (TMS). Prefrontal areas were stimulated whilst participants performed random or predictable sequence learning tasks at stimulus onset (1st presentation of the sequence only for both Random and Predictable), or during the inter-sequence interval. Overall, we found that during the predictable task a significant decrease in saccade latency, gain and duration was found when compared to the randomised conditions, as expected and observed previously. However, TMS stimulation in DLPFC during the delay in the predictive sequence learning task reduced this predictive ability by delaying the saccadic onset and generating abnormal reductions in saccadic gains during prediction. In contrast, we found that stimulation during a delay in MRPFC reversed the normal effects on peak velocity of the task with the predictive task revealing higher peak velocity than the randomised task. These findings provide causal evidence for independent functions of DLPFC and MRPFC in performing stimulus-independent processing during sequence learning in saccades. PMID- 26563165 TI - Dopamine-dependent modulation of rat globus pallidus excitation by nicotine acetylcholine receptors. AB - The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways. PMID- 26563166 TI - The First Case of Invasive Mixed-Mold Infections Due to Emericella nidulans var. echinulata and Rasamsonia piperina in a Patient with Chronic Granulomatous Disease. AB - A 16-year-old boy with chronic granulomatous disease presented with pneumonia and rib osteomyelitis. Emericella nidulans var. echinulata was isolated from his sputum. After starting voriconazole, Rasamsonia piperina was isolated from the rib swelling. A combination therapy of voriconazole and micafungin effectively eradicated this invasive mixed-mold infection. In immunocompromised patients, a precise pathogenic diagnosis is clinically useful for administration of an appropriate treatment regimen. PMID- 26563167 TI - Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid Induced Ulcerative Colitis Remission. AB - BACKGROUND: Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. AIMS: Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. METHODS: Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. RESULTS: Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. CONCLUSIONS: MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209. PMID- 26563169 TI - No difference in patellar kinematics between fixed-bearing cruciate-retaining and cruciate-substituting total knee arthroplasty: a cadaveric investigation. AB - PURPOSE: The influence of cruciate-ligament-retaining (CR-TKA) and cruciate ligament-substituting (CS-TKA) TKA on tibiofemoral kinematics was analysed in many investigations. However, the influence on patellar kinematics is unclear so far. The aim of this study was to compare patellar kinematics of the natural knee with those after CR- and CS-TKA. METHODS: Patellar kinematics of nine healthy whole-body cadaveric knees before and after CR- and CS-TKA was investigated using a commercial optical computer navigation system. Patellar kinematics of the healthy knee was compared with those after CR- and CS-TKA. RESULTS: No significant difference between the natural knee and the knee after TKA or between both types of TKA for patellar kinematics could be found. Interestingly, both types of TKA resulted in a more medial patellar shift and a contrary patellar tilt and rotation behaviour. CR- and CS-TKA resulted in smaller values for patellar epicondylar distance at all flexion angles. CONCLUSIONS: Our study found no influence of prosthesis type on patellar kinematics. Factors like component alignment and prosthesis design seem to be more important in terms of adequate restoration of patellar kinematics in TKA than whether choosing CR- or CS-TKA. PMID- 26563168 TI - Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I. AB - Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of sophisticated systems pharmacology models and improved TCI tools are needed to accurately evaluate patients' exposure to drugs in general and to immunosuppressants in particular. Sequential studies, first without and then with TCI, should be conducted to validate the clinical benefit of TCI in homogenous populations; randomized trials are not feasible, because there are higher-priority research questions in alloHCT. In Part I of this article, we review the alloHCT process to facilitate optimal design of pharmacokinetic and pharmacodynamics studies. We also review the pharmacokinetics and TCI of calcineurin inhibitors and methotrexate. PMID- 26563170 TI - Evidence of perceived psychosocial stress as a risk factor for stroke in adults: a meta-analysis. AB - BACKGROUND: Several studies suggest that perceived psychosocial stress is associated with increased risk of stroke; however results are inconsistent with regard to definitions and measurement of perceived stress, features of individual study design, study conduct and conclusions drawn and no meta-analysis has yet been published. We performed a systematic review and meta-analysis of studies assessing association between perceived psychosocial stress and risk of stroke in adults.The results of the meta-analysis are presented. METHODS: Systematic searches of MEDLINE, EMBASE, CINAHL, PsycInfo, and Cochrane Database of Systematic Reviews were undertaken between 1980 and June 2014. Data extraction and quality appraisal was performed by two independent reviewers. Hazard ratios (HR) and odds ratios (OR) were pooled where appropriate. RESULTS: 14 studies were included in the meta-analysis, 10 prospective cohort, 4 case-control design. Overall pooled adjusted effect estimate for risk of total stroke in subjects exposed to general or work stress or to stressful life events was 1.33 (95 % confidence interval [CI], 1.17, 1.50; P < 0.00001). Sub-group analyses showed perceived psychosocial stress to be associated with increased risk of fatal stroke (HR 1.45 95 % CI, 1.19,1.78; P = 0.0002), total ischaemic stroke (HR 1.40 95 % CI, 1.00,1.97; P = 0.05) and total haemorrhagic stroke (HR 1.73 95 % CI, 1.33,2.25; P > 0.0001).A sex difference was noted with higher stroke risk identified for women (HR 1.90 95 % CI, 1.4, 2.56: P < 0.0001) compared to men (HR 1.24 95 % CI, 1.12, 1.36; P < 0.0001). CONCLUSIONS: Current evidence indicates that perceived psychosocial stress is independently associated with increased risk of stroke. PMID- 26563172 TI - 90 years of perseverance and achievements in biological education and research. PMID- 26563171 TI - Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6 month observational study (EDATE): impact of patient characteristics and comorbidities. AB - BACKGROUND: To explore the impact of patient-characteristics and relevant comorbidities on treatment continuation rates, effectiveness, and satisfaction in patients with erectile dysfunction (ED) who started or switched to tadalafil 5 mg once daily (TAD-OaD) at baseline. METHODS: In the EDATE observational study, phosphodiesterase-type-5 (PDE5)-inhibitor pretreated or naive ED patients who started or switched to TAD-OaD were prospectively followed for 6 months. Time to discontinuation of TAD-OaD was estimated using the Kaplan-Meier product-limit method at Months 2, 4, and 6 in subgroups stratified by age (18 - 65 years and >65 years), PDE5-inhibitor pretreatment, ED-severity (mild, moderate, severe), and presence or absence of relevant comorbidities (BPH, diabetes, CVD, hypertension, dyslipidemia). LSmean change from baseline in International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores and associated 95 % CIs were assessed using a mixed model for repeated measures. Visit, ED etiology, and subgroups were included as fixed-effects. RESULTS: Overall, 778 patients received prescriptions for initiating or switching to TAD-OaD at baseline. At Month 2, >90 % of patients remained on TAD-OaD, except those aged >65 years (86.7 %) and patients with severe ED (89.0 %). More than 80 % of patients in all subgroups, except those aged >65 years (75.0 %), continued TAD-OaD at Month 6. There was a significant LSmean negative effect on IIEF- EF domain-score improvement for BPH (LSmean effect [95 % CI]: -2.77 [-4.98, -0.55], p = 0.014), previous PDE5-inhibitor treatment (-2.13 [-3.33,-0.94], p < 0.001), and mild vs moderate ED (-2.00 [ 3.54,-0.46], p = 0.011); the latter possibly linked with a bigger treatment effect in those with more severe ED at baseline. The LSmean effect on change in IIEF-EF was significantly positive for diabetes (2.28 [0.64,3.92], p = 0.007), most likely because those with diabetes had more severe ED at baseline. For all other parameters, no statistically significant LSmean effects in IIEF-EF changes were observed. No comorbidity or baseline-characteristic except age (18 - 65 years vs >65 years: 11.25 [2.96,19.54], p = 0.008) affected changes in EDITS. CONCLUSIONS: Under routine clinical conditions, treatment continuation rate or satisfaction does not seem to be significantly affected by the presence of comorbidities in men who choose ED-treatment with TAD-OaD. The magnitude of treatment effectiveness was affected by certain baseline characteristics and comorbid conditions. TRIAL REGISTRATION: The study (H6D-EW-LVIU) is registered in the German VfA Registry of Non-Interventional Studies (Verband Forschender Arzneimittelhersteller) since 06 December 2011; available at: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu arzneimitteln/nisdb/nis-details/_741 . PMID- 26563173 TI - Celebrating 90 years of Peking University School of Life Sciences (1925-2015). PMID- 26563175 TI - Unraveling the mechanisms of synapse formation and axon regeneration: the awesome power of C. elegans genetics. AB - Since Caenorhabditis elegans was chosen as a model organism by Sydney Brenner in 1960's, genetic studies in this organism have been instrumental in discovering the function of genes and in deciphering molecular signaling network. The small size of the organism and the simple nervous system enable the complete reconstruction of the first connectome. The stereotypic developmental program and the anatomical reproducibility of synaptic connections provide a blueprint to dissect the mechanisms underlying synapse formation. Recent technological innovation using laser surgery of single axons and in vivo imaging has also made C. elegans a new model for axon regeneration. Importantly, genes regulating synaptogenesis and axon regeneration are highly conserved in function across animal phyla. This mini-review will summarize the main approaches and the key findings in understanding the mechanisms underlying the development and maintenance of the nervous system. The impact of such findings underscores the awesome power of C. elegans genetics. PMID- 26563176 TI - De novo assembly and comparative analysis of root transcriptomes from different varieties of Panax ginseng C. A. Meyer grown in different environments. AB - Panax ginseng C. A. Meyer is an important traditional herb in eastern Asia. It contains ginsenosides, which are primary bioactive compounds with medicinal properties. Although ginseng has been cultivated since at least the Ming dynasty to increase production, cultivated ginseng has lower quantities of ginsenosides and lower disease resistance than ginseng grown under natural conditions. We extracted root RNA from six varieties of fifth-year P. ginseng cultivars representing four different growth conditions, and performed Illumina paired-end sequencing. In total, 163,165,706 raw reads were obtained and used to generate a de novo transcriptome that consisted of 151,763 contigs (76,336 unigenes), of which 100,648 contigs (66.3%) were successfully annotated. Differential expression analysis revealed that most differentially expressed genes (DEGs) were upregulated (246 out of 258, 95.3%) in ginseng grown under natural conditions compared with that grown under artificial conditions. These DEGs were enriched in gene ontology (GO) terms including response to stimuli and localization. In particular, some key ginsenoside biosynthesis-related genes, including HMG-CoA synthase (HMGS), mevalonate kinase (MVK), and squalene epoxidase (SE), were upregulated in wild-grown ginseng. Moreover, a high proportion of disease resistance-related genes were upregulated in wild-grown ginseng. This study is the first transcriptome analysis to compare wild-grown and cultivated ginseng, and identifies genes that may produce higher ginsenoside content and better disease resistance in the wild; these genes may have the potential to improve cultivated ginseng grown in artificial environments. PMID- 26563174 TI - Uridylation and adenylation of RNAs. AB - The posttranscriptional addition of nontemplated nucleotides to the 3' ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3' ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone mRNAs, mRNA fragments, U6 snRNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area. PMID- 26563177 TI - B cells biology in systemic lupus erythematosus-from bench to bedside. AB - Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed. PMID- 26563178 TI - Feasibility of an eHealth application "OncoKompas" to improve personalized survivorship cancer care. AB - PURPOSE: The purpose of this study was to investigate the feasibility of an online self-management application (OncoKompas) among cancer survivors. In OncoKompas, cancer survivors can monitor their quality of life (QOL) via participant reported outcomes (PROs) ("Measure"), which is followed by automatically generated individually tailored feedback ("Learn") and personalized advice on supportive care services ("Act"). METHODS: A pretest-posttest design was used, conducting a survey before providing access to OncoKompas, and 2 weeks after, followed by an interview by a nurse. Adoption was defined as the percentage of cancer survivors that agreed to participate in the study and returned the T0 questionnaire. Implementation was defined as the percentage of participants that actually used OncoKompas as intended (T1). General satisfaction was assessed based on the mean score of three study-specific questions: (1) general impression of OncoKompas, (2) the user-friendliness, and (3) the ability to use OncoKompas without assistance (10-point Likert scales). Furthermore, satisfaction was measured with the Net Promotor Scale (NPS). RESULTS: OncoKompas was feasible with an adoption grade of 64 %, an implementation grade of 75-91 %, a mean satisfaction score of 7.3, and a positive NPS (1.9). Sociodemographic and clinical factors and QOL were not associated with satisfaction. Several facilitators and barriers related to the feasibility of OncoKompas were identified. CONCLUSION: OncoKompas is considered feasible, but has to be further improved. In order to enhance feasibility and increase satisfaction, we have to balance the time it takes to use OncoKompas, measurement precision, and tailoring towards personalized advices. PMID- 26563179 TI - Risk factors for anthracycline-associated cardiotoxicity. AB - PURPOSE: Carbonyl reductase (CBR) catalyzes anthracycline metabolism, and single nucleotide polymorphisms (SNPs) in CBR impact metabolic efficiency. In pediatric patients, homozygosity for the major allele (G) in the CBR3 gene was associated with increased risk of anthracycline cardiotoxicity. We hypothesized that CBR SNPs contribute to cardiotoxicity in adults. METHODS: We retrospectively identified female breast cancer patients in the Columbus Breast Tissue Bank Registry treated with adriamycin and cytoxan (AC) from 2003 to 2012. We selected patients who developed cardiomyopathy, defined as a drop in ejection fraction to <50 % or >15 % decrease from pre-therapy. Univariate and multivariate logistic regressions were performed to identify cardiotoxicity risk factors. SNPs were genotyped, and frequency of the major allele (G)/minor allele (A) of the CBR3 and CBR1 genes was calculated. RESULTS: We identified 52 cases of cardiotoxicity after AC and 110 controls. Multivariate analysis showed that trastuzumab (p = 0.009), diabetes (p = 0.05), and consumption of >8 alcoholic drinks/week (p = 0.024) were associated with higher cardiotoxicity risk. Moderate alcohol consumption (<8 drinks/week) was associated with lower risk (p = 0.009). No association was identified between CBR SNPs and cardiotoxicity (CBR1 p = 0.261; CBR3 p = 0.556). CONCLUSIONS: This is the first study to evaluate SNPs in the CBR pathway as predictors of AC cardiotoxicity in adults. We did not observe any significant correlation between cardiotoxicity and SNPs within the CBR pathway. Further investigation into CBR SNPs in a larger adult sample is needed. Additional exploration into genomic predictors of anthracycline cardiotoxicity may allow for the development of preventative and therapeutic strategies for those at risk. PMID- 26563180 TI - How sedentary and physically active are breast cancer survivors, and which population subgroups have higher or lower levels of these behaviors? AB - PURPOSE: Physical activity (PA) and sedentary behavior may influence the physical and mental health of breast cancer survivors; however, few studies have objectively measured these behaviors in this population. We used accelerometers to measure the PA and sedentary time levels of breast cancer survivors and examined the demographic, behavioral, and medical correlates of these behaviors using two complementary approaches. METHODS: A total of 259 breast cancer survivors wore an accelerometer for 7 days during waking hours and completed a questionnaire. We used linear regression and classification trees to investigate correlates of PA and sedentary time. RESULTS: The breast cancer survivors in this study (mean age = 61 years, mean time since diagnosis = 3 years) were sedentary for a daily average of 8.2 h, in light-intensity PA for 5.8 h and in moderate-to vigorous intensity PA (MVPA) for 32 min, with 16 % meeting PA guidelines. Participants with high comorbidity were the least likely to be meeting guidelines (0 %), while a subgroup of participants with no/low comorbidity, a university degree, and higher levels of pre-diagnosis MVPA were the most likely to be meeting guidelines (47 %). Older participants (70+ years) were the most likely to have sedentary time levels at least twice as high as activity levels, while participants who were younger than 70 years and not in the lowest category of pre diagnosis MVPA were the least likely. CONCLUSIONS: Interventions to facilitate physical activity and reduce sedentary time among breast cancer survivors should consider comorbidity status and previous PA experience. PMID- 26563181 TI - Integrative medicine, quality of life and gynecological cancer : Comments on the article titled "Quality-of-life outcomes in patients with gynecologic cancer referred to integrative oncology treatment during chemotherapy". PMID- 26563182 TI - Quality of life and symptom burden in patients with breast cancer treated with mastectomy and lumpectomy. AB - INTRODUCTION: Mastectomy (MAS) and lumpectomy (LUMP) are the two common local surgical treatments for early breast cancer. There has been a debate whether MAS or LUMP results in better quality of life (QOL). The purpose of this study was to examine the symptom burden (SB) and QOL of both MAS and LUMP patients. METHODS: Patients at the Louise Temerty Breast Cancer Centre in Toronto, Canada, were approached to complete two self-administered questionnaires, the Edmonton Symptom Assessment Score (ESAS) and the Functional Assessment of Cancer Therapy-Breast (FACT-B) cancer edition. Additionally, patient demographics were recorded from medical records. Patients were divided into two cohorts depending on their surgical treatment: MAS and LUMP. The QOL and SB, assessed by FACT-B and ESAS, respectively, of MAS and LUMP patients were compared. The analysis was repeated excluding patients with metastases. RESULTS: From January to August 2014, 614 MAS and 801 LUMP patients were accrued. The MAS patients reported a lower QOL in all categories, except social well-being. There was however no statistical difference in ESAS scores for MAS and LUMP patients with non-metastatic breast cancer. CONCLUSION: This study supports existing literature that SB of MAS and LUMP patients without metastases are similar. QOL of MAS patients including those with metastases was lower than that of LUMP patients. PMID- 26563184 TI - Endoluminal diverticular abscess with endoscopic drainage: a new presentation and management of acute diverticulitis. PMID- 26563183 TI - Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. AB - PURPOSE: The purpose of the study is to examine changes in muscle strength and self-reported physical functioning in men receiving androgen deprivation therapy (ADT) for prostate cancer compared to matched controls. METHODS: Prostate cancer patients scheduled to begin ADT (n = 62) were assessed within 20 days of starting ADT and 6 and 12 months later. Age and geographically matched prostate cancer controls treated with prostatectomy only (n = 86) were assessed at similar time intervals. Grip strength measured upper body strength, the Chair Rise Test measured lower body strength, and the SF-12 Physical Functioning scale measured self-reported physical functioning. RESULTS: As expected, self-reported physical functioning and upper body muscle strength declined in ADT recipients but remained stable in prostate cancer controls. Contrary to expectations, lower body muscle strength remained stable in ADT recipients but improved in prostate cancer controls. Higher Gleason scores, more medical comorbidities, and less exercise at baseline predicted greater declines in physical functioning in ADT recipients. CONCLUSIONS: ADT is associated with declines in self-reported physical functioning and upper body muscle strength as well as worse lower body muscle strength relative to prostate cancer controls. These findings should be included in patient education regarding the risks and benefits of ADT. Findings also underscore the importance of conducting research on ways to prevent or reverse declines in physical functioning in this patient population. PMID- 26563185 TI - Non-neutropenic acute typhlitis associated to gram-positive bacillus: clinicopathological series. PMID- 26563186 TI - Prophylactic stoma mesh did not prevent parastomal hernias. PMID- 26563187 TI - Estimation of extravascular lung water using the transpulmonary ultrasound dilution (TPUD) method: a validation study in neonatal lambs. AB - Increased extravascular lung water (EVLW) may contribute to respiratory failure in neonates. Accurate measurement of EVLW in these patients is limited due to the lack of bedside methods. The aim of this pilot study was to investigate the reliability of the transpulmonary ultrasound dilution (TPUD) technique as a possible method for estimating EVLW in a neonatal animal model. Pulmonary edema was induced in 11 lambs by repeated surfactant lavages. In between the lavages, EVLW indexed by bodyweight was estimated by TPUD (EVLWItpud) and transpulmonary dye dilution (EVLWItpdd) (n = 22). Final EVLWItpud measurements were also compared with EVLWI estimations by gold standard post mortem gravimetry (EVLWIgrav) (n = 6). EVLWI was also measured in two additional lambs without pulmonary edema. Bland-Altman plots showed a mean bias between EVLWItpud and EVLWItpdd of -3.4 mL/kg (LOA +/- 25.8 mL/kg) and between EVLWItpud and EVLWIgrav of 1.7 mL/kg (LOA +/- 8.3 mL/kg). The percentage errors were 109 and 43 % respectively. The correlation between changes in EVLW measured by TPUD and TPDD was r2 = 0.22. Agreement between EVLWI measurements by TPUD and TPDD was low. Trending ability to detect changes between these two methods in EVLWI was questionable. The accuracy of EVLWItpud was good compared to the gold standard gravimetric method but the TPUD lacked precision in its current prototype. Based on these limited data, we believe that TPUD has potential for future use to estimate EVLW after adaptation of the algorithm. Larger studies are needed to support our findings. PMID- 26563189 TI - Quality control and assurance in hematopoietic stem cell transplantation data registries in Japan and other countries. AB - Observational studies from national and international registries with large volumes of patients are commonly performed to identify superior strategies for hematopoietic stem cell transplantation. Major international and national stem cell transplant registries collect outcome data using electronic data capture systems, and a systematic study support process has been developed. Statistical support for studies is available from some major international registries, and international and national registries also mutually collaborate to promote stem cell transplant outcome studies and transplant-related activities. Transplant registries additionally take measures to improve data quality to further improve the quality of outcome studies by utilizing data capture systems and manual data management. Data auditing can potentially even further improve data quality; however, human and budgetary resources can be limiting factors in system construction and audits of the Japanese transplant registry are not currently performed. PMID- 26563188 TI - A simple informative intervention in primary care increases statin adherence. AB - PURPOSE: To assess the effectiveness of an informative intervention on general practitioners aimed at improving patients' adherence to statin therapy. METHODS: In the local health unit (LHU) of Bergamo, Lombardy (Italy), each general practitioner received a synthetic scientific document on dyslipidaemia and statins and aggregated data on adherence in 2006 for his/her patients compared to the means in the LHU and in his/her working district. Furthermore, a sample of seven districts received also a table of adherence levels for single patients. Patient's level data were retrieved from the health care utilisation databases of the LHU. Adherence parameters (proportion of patients with only one prescription, medication possession ratio [MPR] and proportion of non-persistent patients) were assessed after 1 year of follow-up. RESULTS: Overall, 5833 and 4788 new statin users were enrolled before and after the intervention, respectively. The percentage of patients with only one prescription decreased from 28.0 to 23.9 % (p < 0.001). MPR increased from 70.3 to 76.0 % (p < 0.001), and proportion of patients with MPR >= 80 % increased from 45.4 to 56.4 % (p < 0.001). The persistence also showed an improvement, both in terms of decreasing proportion of non-persistent (from 51.9 to 41.4 %, p < 0.001) and of increasing duration of continued therapy (from 235 to 264 mean days of persistent therapy, p < 0.001). There were not significant differences between the two types of intervention. CONCLUSIONS: This intervention resulted in an overall improvement of the short term adherence to therapy. This tool can be replicated in other local contexts and with other chronic therapies. PMID- 26563190 TI - High-dose cytarabine salvage therapy for recurrent primary CNS lymphoma. AB - Treatment of recurrent primary CNS lymphoma (PCNSL) though not standardized most often utilizes whole brain radiotherapy, re-challenge with high-dose methotrexate, or administration of an alkylating chemotherapy. High-dose cytarabine (HD-araC) has been advocated as an active agent in PCNSL but limited information exists regarding single agent activity in the recurrent setting. A retrospective review of 14 patients (10 males, 4 females: median age 60 years) with recurrent PCNSL treated at second recurrence with single agent HD-araC. HD araC was administered at 3gm/m(2) over a 3-h infusion every 12 h for a total of 4 doses (defined as a cycle of therapy). GM-CSF was administered at conclusion of HD-araC. Patients were clinically and radiographically evaluated every 4-weeks. Common toxicity criteria Grade 3 or 4 toxicity included thrombocytopenia (11 patients; 79%), anemia (10; 71%), fatigue (8; 57%), mucositis (8; 57%), neutropenia (8; 57%) and neutropenic fever (5; 36%). No patient discontinued therapy due to toxicity nor were there any treatment-related deaths. Best response to HD-araC was stable disease in 6 patients (43%), partial response in 5 (36%) and progressive disease in 3 (21%). Median progression free survival 3 months (range 2-5 months; 95% CI 2-4 months) and progression free survival was 0% at 6-months. Median survival after onset of HD-araC was 12 months (range 3-18+ months; 95% CI 3-15 months). Single agent HD-araC has limited activity in recurrent PCNSL and is associated with significant toxicity in this small retrospective study. PMID- 26563192 TI - Volume-Based Enteral Nutrition Support Regimen Improves Caloric Delivery but May Not Affect Clinical Outcomes in Critically Ill Patients. AB - INTRODUCTION: Meeting enteral nutrition goals is an ongoing challenge in the intensive care unit (ICU). Most hospitals use rate-based (RB) protocols for nutrient delivery. Previous studies have found that volume-based (VB) protocols improve delivery of prescribed calories. However, these studies did not assess clinical outcomes. We hypothesize that a VB method will improve the delivery of prescribed calories and lead to improved clinical outcomes. METHODS: A before-and after study was performed following implementation of a VB feeding protocol in an adult mixed medical-surgical ICU. Formal institutional review board approval was obtained. The effect of RB and VB protocols on percentage of goal calories received, ICU length of stay (LOS), hospital LOS, mortality, days on the ventilator, and rates of infection were investigated using the Kruskal-Wallis test of differences. Multivariate regression was used to identify independent predictors of outcome. Significance was defined as P < .05. RESULTS: A total of 77 patients were included (RB = 39, VB = 38). There were no differences in demographics between the 2 groups with the exception of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, which was significantly higher in the VB group. VB patients received significantly more prescribed calories (74% vs 57%, P < .001). VB patients had significantly longer ICU LOS and duration of mechanical ventilation on univariate analysis. These differences did not persist after controlling for APACHE II score. CONCLUSION: VB enteral feeding allows for a significantly greater provision of prescribed calories but may not affect clinical outcomes. A larger sample size is needed for adequate power to corroborate these findings. PMID- 26563191 TI - Coibamide A, a natural lariat depsipeptide, inhibits VEGFA/VEGFR2 expression and suppresses tumor growth in glioblastoma xenografts. AB - Coibamide A is a cytotoxic lariat depsipeptide isolated from a rare cyanobacterium found within the marine reserve of Coiba National Park, Panama. Earlier testing of coibamide A in the National Cancer Institute in vitro 60 human tumor cell line panel (NCI-60) revealed potent anti-proliferative activity and a unique selectivity profile, potentially reflecting a new target or mechanism of action. In the present study we evaluated the antitumor activity of coibamide A in several functional cell-based assays and in vivo. U87-MG and SF-295 glioblastoma cells showed reduced migratory and invasive capacity and underwent G1 cell cycle arrest as, likely indirect, consequences of treatment. Coibamide A inhibited extracellular VEGFA secreted from U87-MG glioblastoma and MDA-MB-231 breast cancer cells with low nM potency, attenuated proliferation and migration of normal human umbilical vein endothelial cells (HUVECs) and selectively decreased expression of vascular endothelial growth factor receptor 2 (VEGFR2). We report that coibamide A retains potent antitumor properties in a nude mouse xenograft model of glioblastoma; established subcutaneous U87-MG tumors failed to grow for up to 28 days in response to 0.3 mg/Kg doses of coibamide A. However, the natural product was also associated with varied patterns of weight loss and thus targeted delivery and/or medicinal chemistry approaches will almost certainly be required to improve the toxicity profile of this unusual macrocycle. Finally, similarities between coibamide A- and apratoxin A-induced changes in cell morphology, decreases in VEGFR2 expression and macroautophagy signaling in HUVECs raise the possibility that both cyanobacterial natural products share a common mechanism of action. PMID- 26563193 TI - Extra L8bn to NHS cannot fund seven day service, MPs hear. PMID- 26563194 TI - The Challenge of Erectile Dysfunction Management in the Young Man. AB - Erectile dysfunction (ED) in a young man is an important health problem that significantly impacts the patient's quality of life and can have a detrimental effect on his well-being and relationship with his partner. Erectile dysfunction or impotence is one of the few disorders that will bring a young man into the doctor's office. This review article focuses on the epidemiology, etiology, presentation, work-up, and treatment of young men (age ~20-40 years old) presenting with complaints of ED. It is important to identify the precise etiology of the ED before proceeding with further evaluation and treatment because the work-up can be invasive and costly. ED is estimated to affect 20 % of men above 40 years of age, with the incidence increasing with increasing age. Erectile dysfunction has traditionally been seen as an age-dependent problem; however, approximately 2 % of men are affected at 40 years of age but this may be a gross underestimation secondary to reporting bias. Because ED is traditionally seen in the aging male population, studies regarding ED tend to be more frequently carried out among middle-aged and elderly men rather than in young men. These studies underline how comorbidities such as diabetes mellitus, cardiovascular or neurological pathologies, and medication use are strongly linked with ED. In addition, ED has been described to be associated with obesity or physical inactivity. This review article summarizes the important information that all sexual medicine providers should be familiar with when diagnosing, counseling, and treating young men with erectile dysfunction. PMID- 26563195 TI - Olfactory Reference Disorder: Diagnosis, Epidemiology and Management. AB - Although not included as a disorder in the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition), olfactory reference disorder (ORD) is being considered for inclusion as a discrete disorder in the ICD-11 (International Classification of Diseases, 11th edition). ORD is likely underdiagnosed and undertreated. The purpose of this paper is to provide information to clinicians and researchers on the epidemiology, clinical presentation and treatment options for this condition. A narrative overview of the literature as retrieved from a computerized database search is provided. ORD is a condition that is characterized by the erroneous belief that one emits a foul or unpleasant body odour, resulting in significant distress and impairment. It is often accompanied by referential thinking and repetitive behaviours aimed at camouflaging the perceived odour. Level of insight varies, with some patients having concerns that are delusional. Patients usually do not spontaneously report their symptoms and so screening in suspected cases is crucial. The literature regarding ORD treatment remains limited. PMID- 26563197 TI - The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial. AB - BACKGROUND: A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. METHODS/DESIGN: We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. DISCUSSION: This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. TRIAL REGISTRATION: Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030. PMID- 26563196 TI - Oral Targeted Therapies and Central Nervous System (CNS) Metastases. AB - The purpose of our review is to summarize the clinical activity of oral targeted agents against brain metastases. This includes BRAF inhibitors (dabrafenib and vemurafenib), human epidermal growth factor receptor inhibitors (lapatinib, gefitinib, erlotinib, and afatinib), multi-kinase angiogenesis inhibitors (sorafenib, sunitinib, pazopanib, and vandetanib), and ALK/c-MET (crizotinib) and ALK/IGF-1 (ceritinib) inhibitors. Effective systemic therapies are needed for long-term benefit in brain metastases and documentation of intracranial activity for many therapies is poor. Our review provides a summary of the literature with pertinent data for clinicians. This is needed as subjects with brain metastases are often prevented from enrolling in clinical trials and investigations focused on systemic therapies for brain metastases are rare. PMID- 26563198 TI - A mathematical model for estimating the axial stress of the common carotid artery wall from ultrasound images. AB - Clarifying the complex interaction between mechanical and biological processes in healthy and diseased conditions requires constitutive models for arterial walls. In this study, a mathematical model for the displacement of the carotid artery wall in the longitudinal direction is defined providing a satisfactory representation of the axial stress applied to the arterial wall. The proposed model was applied to the carotid artery wall motion estimated from ultrasound image sequences of 10 healthy adults, and the axial stress waveform exerted on the artery wall was extracted. Consecutive ultrasonic images (30 frames per second) of the common carotid artery of 10 healthy subjects (age 44 +/- 4 year) were recorded and transferred to a personal computer. Longitudinal displacement and acceleration were extracted from ultrasonic image processing using a block matching algorithm. Furthermore, images were examined using a maximum gradient algorithm and time rate changes of the internal diameter and intima-media thickness were extracted. Finally, axial stress was estimated using an appropriate constitutive equation for thin-walled tubes. Performance of the proposed model was evaluated using goodness of fit between approximated and measured longitudinal displacement statistics. Values of goodness-of-fit statistics indicated high quality of fit for all investigated subjects with the mean adjusted R-square (0.86 +/- 0.08) and root mean squared error (0.08 +/- 0.04 mm). According to the results of the present study, maximum and minimum axial stresses exerted on the arterial wall are 1.7 +/- 0.6 and -1.5 +/- 0.5 kPa, respectively. These results reveal the potential of this technique to provide a new method to assess arterial stress from ultrasound images, overcoming the limitations of the finite element and other simulation techniques. PMID- 26563199 TI - Fluid flow and particle transport in mechanically ventilated airways. Part I. Fluid flow structures. AB - A large eddy simulation-based computational study of fluid flow and particle transport in upper tracheobronchial airways is carried out to investigate the effect of ventilation parameters on pulmonary fluid flow. Respiratory waveforms commonly used by commercial mechanical ventilators are used to study the effect of ventilation parameters and ventilation circuit on pulmonary fluid dynamics. A companion paper (Alzahrany et al. in Med Biol Eng Comput, 2014) reports our findings on the effect of the ventilation parameters and circuit on particle transport and aerosolized drug delivery. The endotracheal tube (ETT) was found to be an important geometric feature and resulted in a fluid jet that caused an increase in turbulence and created a recirculation zone with high wall shear stress in the main bronchi. Stronger turbulence was found in lower airways than would be found under normal breathing conditions due to the presence of the jet caused by the ETT. The pressure-controlled sinusoidal waveform induced the lowest wall shear stress on the airways wall. PMID- 26563200 TI - The role of pre-symbiotic auxin signaling in ectendomycorrhiza formation between the desert truffle Terfezia boudieri and Helianthemum sessiliflorum. AB - The ectendomycorrhizal fungus Terfezia boudieri is known to secrete auxin. While some of the effects of fungal auxin on the plant root system have been described, a comprehensive understanding is still lacking. A dual culture system to study pre mycorrhizal signal exchange revealed previously unrecognized root-fungus interaction mediated by the fungal auxin. The secreted fungal auxin induced negative taproot gravitropism, attenuated taproot growth rate, and inhibited initial host development. Auxin also induced expression of Arabidopsis carriers AUX1 and PIN1, both of which are involved in the gravitropic response. Exogenous application of auxin led to a root phenotype, which fully mimicked that induced by ectomycorrhizal fungi. Co-cultivation of Arabidopsis auxin receptor mutants tir1-1, tir1-1 afb2-3, tir1-1 afb1-3 afb2-3, and tir1-1 afb2-3 afb3-4 with Terfezia confirmed that auxin induces the observed root phenotype. The finding that auxin both induces taproot deviation from the gravity axis and coordinates growth rate is new. We propose a model in which the fungal auxin induces horizontal root development, as well as the coordination of growth rates between partners, along with the known auxin effect on lateral root induction that increases the availability of accessible sites for colonization at the soil plane of fungal spore abundance. Thus, the newly observed responses described here of the root to Terfezia contribute to a successful encounter between symbionts. PMID- 26563201 TI - Discordant cardiac biomarker levels independently predict outcome in ST-segment elevation myocardial infarction. AB - AIMS: To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-segment elevation myocardial infarction (STEMI) without significant creatine kinase (CK) elevation on admission. METHODS AND RESULTS: From January 1, 2002 to December 31, 2006 patients with STEMI without significant CK elevation (<2-fold) on admission treated with percutaneous coronary intervention (PCI) were included and stratified according to cTnT plasma levels. Univariate and multivariate regression analyses were used to find independent predictors for mortality. During the 5-year period 514 patients with STEMI and normal CK plasma levels were included. 308 (59.9 %) patients had cTnT levels <0.1 MUg/l and 206 (40.1 %) patients had cTnT levels >=0.1 MUg/l. Multivariate logistic regression analysis identified cTnT levels >=0.1 MUg/l and 3-vessel disease as positive, and hemoglobin levels as negative independent predictors for long-term mortality. Discordantly elevated cTnT plasma levels independently predicted higher mortality rates in the first year (HR 3.9, 95 % CI 1.7-9.1, p = 0.002) and during 5 years (HR 2.3, 95 % CI 1.4-3.9, p = 0.002) after PCI for STEMI. CONCLUSIONS: Discordant elevation of cTnT in the presence of normal CK plasma levels on admission is associated with increased mortality in STEMI patients undergoing primary PCI. This may be due to preceding microembolization. PMID- 26563202 TI - Olfactory Cues from Pathogenic Fungus Affect the Direction of Motion of Termites, Coptotermes formosanus. AB - Formosan subterranean termites, Coptotermes formosanus, tend to avoid pathogen odors when tested in Y-tube olfactometers, but approach and groom exposed nestmates to remove pathogens from their cuticle and maintain a healthy population. To better understand their differential reaction to pathogens and their odors, the relationship between odor cues and direction of motion was examined with the fungus Isaria fumosorosea K3 strain. The results indicate that nestmate odor was strongly attractive only in tests where fungal odors were present in both branches of the olfactometer. Termites generally avoid fungal odors when offered a choice without fungal odor. We also tested termite aversion to 3-octanone and 1-octen-3-ol, major surface chemical compounds of I. fumosorosea K3, and estimated the total mass of these compounds present on the conidial surface by direct extraction method. The total quantity of these chemicals on the surface of fungal conidia was estimated to be approximately 0.01 ng per 10(7) conidia. This study demonstrates a context dependent behavioral change in termites in response to the odors of pathogenic fungi. PMID- 26563203 TI - Comparative Herbivory Rates and Secondary Metabolite Profiles in the Leaves of Native and Non-Native Lonicera Species. AB - Non-native plants introduced to new habitats can have significant ecological impact. In many cases, even though they interact with the same community of potential herbivores as their new native competitors, they regularly receive less damage. Plants produce secondary metabolites in their leaves that serve a range of defensive functions, including resistance to herbivores and pathogens. Abiotic factors such as nutrient availability can influence the expression of defensive traits, with some species exhibiting increased chemical defense in low-nutrient conditions. Plants in the genus Lonicera are known to produce a diverse array of these secondary metabolites, yet non-native Lonicera species sustain lower amounts of herbivore damage than co-occurring native Lonicera species in North America. In this study, we searched for evidence of biochemical novelty in non native species, and quantified its association with resistance to herbivores. In order to achieve this, we evaluated the phenolic and iridoid glycoside profiles in leaves of native and non-native Lonicera species grown under high and low fertilization treatments in a common garden. We then related these profiles to naturally occurring herbivore damage on whole plants in the garden. Herbivore damage was greater on native Lonicera, and chemical profiles and concentrations of selected putative defense compounds varied by species. Geographic origin was an inconsistent predictor of chemical variation in detected phenolics and iridoid glycosides (IGs). Overall, fertilization did not affect herbivore damage or measures of phenolics or IGs, but there were some fertilization effects within species. While we cannot conclude that non-natives were more chemically novel than native Lonicera species, chemical defense profiles and concentrations of specific compounds varied by species. Reduced attraction or deterrence of oviposition, specific direct resistance traits, or a combination of both may contribute to reduced herbivory and competitive advantages for non-native Lonicera in North America. PMID- 26563204 TI - Temporally and Spatially Resolved x-ray Fluorescence Measurements of in-situ Drug Concentration in Metered-Dose Inhaler Sprays. AB - PURPOSE: Drug concentration measurements in MDI sprays are typically performed using particle filtration or laser scattering. These techniques are ineffective in proximity to the nozzle, making it difficult to determine how factors such as nozzle design will affect the precipitation of co-solvent droplets in solution based MDIs, and the final particle distribution. METHODS: In optical measurements, scattering from the constituents is difficult to separate. We present a novel technique to directly measure drug distribution. A focused x-ray beam was used to stimulate x-ray fluorescence from the bromine in a solution containing 85% HFA, 15% ethanol co-solvent, and 1 [Formula: see text] / [Formula: see text] IPBr. RESULTS: Instantaneous concentration measurements were obtained with 1 ms temporal resolution and 5 [Formula: see text] spatial resolution, providing information in a region that is inaccessible to many other diagnostics. The drug remains homogeneously mixed over time, but was found to be higher at the centerline than at the periphery. This may have implications for oropharyngeal deposition in vivo. CONCLUSIONS: Measurements in the dynamic, turbulent region of MDIs allow us to understand the physical links between formulation, inspiration, and geometry on final particle size and distribution. This will ultimately lead to a better understanding of how MDI design can be improved to enhance respirable fraction. PMID- 26563205 TI - Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations. AB - PURPOSE: The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations. METHODS: The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions. RESULTS: Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization. CONCLUSIONS: Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization. PMID- 26563206 TI - Monoclonal Antibodies Follow Distinct Aggregation Pathways During Production Relevant Acidic Incubation and Neutralization. AB - PURPOSE: Aggregation aspects of therapeutic monoclonal antibodies (mAbs) are of common concern to the pharmaceutical industry. Low pH treatment is applied during affinity purification and to inactivate endogenous retroviruses, directing interest to the mechanisms of acid-induced antibody aggregation. METHODS: We characterized the oligomerization kinetics at pH 3.3, as well as the reversibility upon neutralization, of three model mAbs with identical variable regions, representative of IgG1, IgG2 and IgG4 respectively. We applied size exclusion high performance liquid chromatography and orthogonal analytical methods, including small-angle X-ray scattering and dynamic light scattering and supplemented the experimental data with crystal structure-based spatial aggregation propensity (SAP) calculations. RESULTS: We revealed distinct solution behaviors between the three mAb models: At acidic pH IgG1 retained monomeric, whereas IgG2 and IgG4 exhibited two-phase oligomerization processes. After neutralization, IgG2 oligomers partially reverted to the monomeric state, while on the contrary, IgG4 oligomers tended to aggregate. Subclass-specific aggregation-prone motifs on the Fc fragments were identified, which may lead to two distinct pathways of reversible and irreversible aggregation, respectively. CONCLUSIONS: We conclude that subtle variations in mAb sequence greatly affect responses towards low-pH incubation and subsequent neutralization, and demonstrate how orthogonal biophysical methods distinguish between reversible and irreversible mAb aggregation pathways at early stages of acidic treatment. PMID- 26563207 TI - Polycyclic aromatic hydrocarbons (PAHs) in multimedia environment of Heshan coal district, Guangxi: distribution, source diagnosis and health risk assessment. AB - Mining activities are among the major culprits of the wide occurrences of soil and water pollution by PAHs in coal district, which have resulted in ecological fragilities and health risk for local residents. Sixteen PAHs in multimedia environment from the Heshan coal district of Guangxi, South China, were measured, aiming to investigate the contamination level, distribution and possible sources and to estimate the potential health risks of PAHs. The average concentrations of 16 PAHs in the coal, coal gangue, soil, surface water and groundwater were 5114.56, 4551.10, 1280.12 ng g(-1), 426.98 and 381.20 ng L(-1), respectively. Additionally, higher soil and water PAH concentrations were detected in the vicinities of coal or coal gangue dump. Composition analysis, isomeric ratio, Pearson correlation analysis and principal component analysis were performed to diagnose the potential sources of PAHs in different environmental matrices, suggesting the dominant inputs of PAHs from coal/coal combustion and coal gangue in the soil and water. Soil and water guidelines and the incremental lifetime risk (ICLR) were used to assess the health risk, showing that soil and water were heavily contaminated by PAHs, and mean ICLRcoal/coal-gangue and mean ICLRsoil were both significantly higher than the acceptable levels (1 * 10(-4)), posing high potential carcinogenic risk to residents, especially coal workers. This study highlights the environmental pollution problems and public health concerns of coal mining, particularly the potential occupational health hazards of coal miners exposed in Heshan. PMID- 26563208 TI - Distribution and geological sources of selenium in environmental materials in Taoyuan County, Hunan Province, China. AB - The selenium (Se) distribution and geological sources in Taoyuan County, China, were determined by using hydride generation atomic fluorescence spectrometry on rock, soil, and food crop samples collected from various geological regions within the county. The results show Se contents of 0.02-223.85, 0.18-7.05, and 0.006-5.374 mg/kg in the rock, soil, and food crops in Taoyuan County, respectively. The region showing the highest Se content is western Taoyuan County amid the Lower Cambrian and Ediacaran black rock series outcrop, which has banding distributed west to east. A relatively high-Se environment is found in the central and southern areas of Taoyuan County, where Quaternary Limnetic sedimentary facies and Neoproterozoic metamorphic volcanic rocks outcrop, respectively. A relatively low-Se environment includes the central and northern areas of Taoyuan County, where Middle and Upper Cambrian and Ordovician carbonate rocks and Cretaceous sandstones and conglomerates outcrop. These results indicate that Se distribution in Taoyuan County varies markedly and is controlled by the Se content of the bedrock. The Se-enriched Lower Cambrian and Ediacaran black rock series is the primary source of the seleniferous environment observed in Taoyuan County. Potential seleniferous environments are likely to be found near outcrops of the Lower Cambrian and Ediacaran black rock series in southern China. PMID- 26563209 TI - Leveling Mountains: Purpose Attenuates Links Between Perceptions of Effort and Steepness. AB - People tend to overestimate the steepness of slopes, especially when they appraise the effort necessary to ascend them as greater. Recent studies, however, suggest the way individuals perceive visual stimuli may rely heavily on their personal motivations. In four studies (N = 517), purpose in life was tested as a motivational framework influencing how appraised effort relates to slope perception. Studies 1 and 2 found the amount of effort participants appraised necessary to ascend several virtual slopes was related to greater overestimation of their steepness. Yet, this relationship was attenuated by purpose assessed both as a disposition and experimental manipulation. Studies 3 and 4 replicated these findings using actual hills, again showing links between the amount of effort thought required to ascend them and their perceived angle were diminished by greater purpose. The discussion addresses implications of purpose as a broad motivational framework that shapes how individuals see their environment. PMID- 26563210 TI - Deaths after elective repair of abdominal aortic aneurysm fall to all time low. PMID- 26563211 TI - The Capillary Index Score before thrombectomy: an angiographic correlate of favorable outcome. AB - BACKGROUND AND PURPOSE: The angiography based Capillary Index Score (CIS) has recently emerged as a potential surrogate marker of cerebral perfusion before intra-arterial thrombolysis. We assessed the prevalence of a favorable CIS (f CIS) and its relationship with clinical outcome in patients treated by mechanical thrombectomy (MT). METHODS: Data from consecutive patients treated by MT from acute middle cerebral artery (MCA) occlusion were retrospectively analyzed. CIS was calculated from a pre-intervention cerebral angiogram. Association with favorable clinical outcome (modified Rankin Scale score <=2) at 3 months was assessed in multivariate analysis. RESULTS: 146 patients were included in the study. f-CIS was observed in 106/146 (72%) patients with an acceptable inter rater agreement (kappa=0.73, p<0.001). It was associated with a lower pretreatment National Institutes of Health Stroke Scale (NIHSS) score (p=0.014), an isolated M1/M2 occlusion without internal carotid occlusion (p=0.042), and an Alberta Stroke Program Early CT Score (ASPECTS) >4 (p=0.004). In binary regression, a favorable outcome was independently associated with f-CIS (OR (-95% CI, +95% CI)=3.8 (1.3 to 10.9), p=0.013), as well as NIHSS (p=0.007), ASPECTS (p=0.005), isolated M1/M2 occlusion (p=0.013), and age (p=0.032). The positive predictive value of f-CIS for a favorable outcome was 67%. CONCLUSIONS: f-CIS was strongly associated with a favorable outcome after MT of acute MCA occlusion. As an easy surrogate marker of cerebral perfusion, it may be a useful-albeit not sufficient-diagnostic test to select patients just before an MT or to manage them after recanalization. PMID- 26563212 TI - Heavy smoking rate trends and related factors in Korean occupational groups: analysis of KNHANES 2007-2012 data. AB - OBJECTIVES: The present study was designed to investigate the smoking and heavy smoking trends and identify possible related factors among Korean male workers from 2007 to 2012 by occupational groups. METHODS: The data were derived from the fourth (2007-2009) and fifth (2010-2012) waves of the Korean National Health and Nutrition Examination Survey (KNHANES). Occupational groups were categorised into three groups, which were non-manual, manual and service and sales groups. Age adjusted prevalence rates of smoking and heavy smoking (>20 cigarettes/day) in men aged 25-64 years were calculated. Factors associated with heavy smoking were investigated using logistic regression analyses. RESULTS: Smoking rate in manual workers decreased gradually over time (p for trend <0.0001). Smoking rate was higher in manual than non-manual workers, but the difference reduced over time (p for trend <0.0001). Heavy smoking rate decreased from 2007 to 2012 (p for trend <0.0001). Heavy smoking rate was higher in manual than non-manual workers; however, this difference increased over time. Stress, depressive mood and long working hours (>=60 h/week) were associated with heavy smoking. CONCLUSIONS: Antismoking policy should focus on current and heavy smokers. Workplace antismoking programmes should consider working hours and stress, especially in manual workers. PMID- 26563213 TI - Associations between chronic diseases and choking deaths among older adults in the USA: a cross-sectional study using multiple cause mortality data from 2009 to 2013. AB - OBJECTIVES: To examine whether the strengths of the associations between chronic diseases and overall choking differ from those of the associations between chronic diseases and only food-related choking. DESIGN: This cross-sectional study used nationwide multiple cause mortality files. SETTING: The USA. PARTICIPANTS: Older adults aged 65 years or more died between 2009 and 2013. MAIN OUTCOME MEASURES: Mortality ratio (observed/expected) of number of deaths from both causes (chronic diseases and choking) and 95% CIs. RESULTS: We identified 76543 deaths for which the death certificates report choking (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes W78, W79 and W80 combined) as a cause of death and only 4974 (6.5%) deaths were classified as food-related choking (ICD-10 code W79). Schizophrenia, Parkinson's disease, Alzheimer's disease and oral cancer are four chronic diseases that had significant associations with both overall and food related choking. Stroke, larynx cancer and mood (affective) disorders had significant associations with overall choking, but not with food-related choking. CONCLUSIONS: We suggest using overall choking instead of only food-related choking to better describe the associations between chronic diseases and choking. PMID- 26563214 TI - Clinical trial registration, reporting, publication and FDAAA compliance: a cross sectional analysis and ranking of new drugs approved by the FDA in 2012. AB - OBJECTIVE: To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. DESIGN: Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. DATA SOURCES: Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. MAIN OUTCOME MEASURES: Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. RESULTS: The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32-83%) of trials were registered, 20% (IQR 12-28%) reported results in ClinicalTrials.gov, 56% (IQR 41-83%) were published, and 65% (IQR 41 83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8-20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0-100%) were FDAAA-compliant. 68% of research participants (67,629 of 99,599) participated in FDAAA-subject trials, with 51% (33,405 of 67,629) enrolled in non-compliant trials. Transparency varied widely among companies. CONCLUSIONS: Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. PMID- 26563215 TI - Navigating Bioethical Waters: Two Pilot Projects in Problem-Based Learning for Future Bioscience and Biotechnology Professionals. AB - We believe that the professional responsibility of bioscience and biotechnology professionals includes a social responsibility to contribute to the resolution of ethically fraught policy problems generated by their work. It follows that educators have a professional responsibility to prepare future professionals to discharge this responsibility. This essay discusses two pilot projects in ethics pedagogy focused on particularly challenging policy problems, which we call "fractious problems". The projects aimed to advance future professionals' acquisition of "fractious problem navigational" skills, a set of skills designed to enable broad and deep understanding of fractious problems and the design of good policy resolutions for them. A secondary objective was to enhance future professionals' motivation to apply these skills to help their communities resolve these problems. The projects employed "problem based learning" courses to advance these learning objectives. A new assessment instrument, "Skills for Science/Engineering Ethics Test" (SkillSET), was designed and administered to measure the success of the courses in doing so. This essay first discusses the rationale for the pilot projects, and then describes the design of the pilot courses and presents the results of our assessment using SkillSET in the first pilot project and the revised SkillSET 2.0 in the second pilot project. The essay concludes with discussion of observations and results. PMID- 26563216 TI - Using Insights from Applied Moral Psychology to Promote Ethical Behavior Among Engineering Students and Professional Engineers. AB - In this essay I discuss a novel engineering ethics class that has the potential to significantly decrease the likelihood that students (and professionals) will inadvertently or unintentionally act unethically in the future. This class is different from standard engineering ethics classes in that it focuses on the issue of why people act unethically and how students (and professionals) can avoid a variety of hurdles to ethical behavior. I do not deny that it is important for students to develop cogent moral reasoning and ethical decision making as taught in traditional college-level ethics classes, but as an educator, I aim to help students apply moral reasoning in specific, real-life situations so they are able to make ethical decisions and act ethically in their academic careers and after they graduate. Research in moral psychology provides evidence that many seemingly irrelevant situational factors affect the moral judgment of most moral agents and frequently lead agents to unintentionally or inadvertently act wrongly. I argue that, in addition to teaching college students moral reasoning and ethical decision-making, it is important to: 1. Teach students about psychological and situational factors that affect people's ethical judgments/behaviors in the sometimes stressful, emotion-laden environment of the workplace; 2. Guide students to engage in critical reflection about the sorts of situations they personally might find ethically challenging before they encounter those situations; and 3. Provide students with strategies to help them avoid future unethical behavior when they encounter these situations in school and in the workplace. PMID- 26563217 TI - Suture Versus Mesh Repair in Primary and Incisional Ventral Hernias: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Today, ventral hernia repair is predominantly performed with meshes. There is no meta-analysis of high quality evidence that compares the results of suture to mesh repair. The objective of this systematic review with meta-analysis is to compare patient centred outcomes of suture versus mesh repair. METHODS: A systematic literature search was performed in EMBASE, MEDLINE and CENTRAL (inception to 06/2014). Furthermore a hand search was performed. RCTs comparing suture versus mesh repair in primary and incisional ventral hernia repair were included. Data on patient characteristics, interventions and results were extracted in standardized tables. Risk of bias was assessed with the cochrane risk of bias tool. Results of studies were pooled with a meta-analysis. All steps were performed by two reviewers. Discrepancies were discussed until a consensus. RESULTS: The search in the databases resulted in 1560 hits. After screening, 10 randomized controlled trials including 1215 patients satisfied all inclusion criteria. Risk of bias was moderate to high. The relative risk for recurrence was 0.36 [95% CI (0.27, 0.49); I (2) = 0; heterogeneity p = 0.70]. Other complications did not differ significantly. Results for chronic pain were heterogeneous across studies. CONCLUSION: Mesh repair reduces the number of recurrences significantly. In patients without recurrence mesh repairs seem to be associated with a risk of chronic pain especially if the mesh is fixed sublay. PMID- 26563218 TI - Cholecystectomy During the Weekend Increases Patients' Length of Hospital Stay. AB - BACKGROUND: A higher risk of complications and mortality has previously been proven in selected settings. The purpose of this study was to investigate whether length of stay differentiates throughout the week and register if intra- and postoperative complications vary on weekends compared to weekdays. METHODS: The population originated from the Danish Cholecystectomy Database. It consists of adult patients, who had a cholecystectomy performed by standard four-port laparoscopic or open surgery. Adjusted analyses were used to study if day of the week had an influence on conversion, readmission within 30 days, post-operative supplemental procedures within 30 days, and variance in postoperative length of stay across the week. RESULTS: A total of 28,759 patients were included in the study. We found no difference in conversion rate, readmission within 30 days, or post-operative procedures within 30 days between week time and weekend time. A longer postoperative length of stay was observed for patients operated on Fridays and Saturdays even though surgical complication rates were alike between weekdays. Patients with acute cholecystitis had a longer length of stay on Saturdays. CONCLUSION: We found no evidence of a higher risk of conversions, post operative procedures, or readmission during weekends compared with weekdays. Despite this, a prolonged length of stay was observed in patients operated with cholecystectomy on Fridays and Saturdays. The observed difference could be due to ward rounds on weekends mainly focus on the sickest patients leaving less time for discharge. PMID- 26563219 TI - Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism. AB - BACKGROUND: Reoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated. METHODS: We retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue. RESULTS: Of 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146). CONCLUSIONS: In patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX. PMID- 26563220 TI - Use of HIV counseling and testing and family planning services among postpartum women in Kenya: a multicentre, non-randomised trial. AB - BACKGROUND: Addressing the postnatal needs of new mothers is a neglected area of care throughout sub-Saharan Africa. The study compares the effectiveness of integrating HIV and family planning (FP) services into postnatal care (PNC) with stand-alone services on postpartum women's use of HIV counseling and testing and FP services in public health facilities in Kenya. METHODS: Data were derived from samples of women who had been assigned to intervention or comparison groups, had given birth within the previous 0-10 weeks and were receiving postnatal care, at baseline and 15 months later. Descriptive statistics describe the characteristics of the sample and multivariate logistic regression models assess the effect of the integrated model of care on use of provider-initiated testing and counseling (PITC) and FP services. RESULTS: At the 15-month follow-up interviews, more women in the intervention than comparison sites used implants (15 % vs. 3 %; p < 0.001), while injectables were the most used short-term method by women in both sites. Women who wanted to wait until later to have children (OR = 1.3; p < 0.01; 95 % CI: 1.1-1.5), women with secondary education (OR = 1.2; p < 0.05; 95 % CI: 1.0-1.4), women aged 25-34 years (OR = 1.2; p < 0.01; 95 % CI: 1.1-1.4) and women from poor households (OR = 1.6; p < 0.001; 95 % CI: 1.4-1.9) were associated with FP use. Nearly half (47 %) and about one-third (30 %) of mothers in the intervention and comparison sites, respectively, were offered PITC. Significant predictors of uptake of PITC were seeking care in a health center/dispensary relative to a hospital, having a partner who has tested for HIV and being poor. CONCLUSIONS: An integrated delivery approach of postnatal services is beneficial in increasing the uptake of PITC and long-acting FP services among postpartum women. Also, interventions aimed at increasing male partners HIV testing have a positive effect on the uptake of PITC and should be encouraged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694862. PMID- 26563221 TI - Capsule Commentary on Bloom-Feshbach et al., Health Literacy in Transitions of Care: An Innovative Objective Structured Clinical Examination for Fourth Year Medical Students in an Internship Preparation Course. PMID- 26563223 TI - Long-term results after treatment of the ascending aorta for bicuspid aortic valve patients. AB - PURPOSE: We evaluated the long-term results of aortic valve replacement for bicuspid aortic valve patients with or without surgical treatment of the ascending aorta. METHODS: A total of 145 bicuspid aortic valve patients had undergone aortic valve replacement since 1974 at our institution. No surgical treatment (Group-N; n = 115) was performed in the ascending aorta if the diameter was less than 40 mm. We wrapped an ascending aorta of 40-50 mm with an artificial graft (Group-W; n = 19), and performed replacement (Group-R; n = 11) if the ascending aorta measured more than 50 mm. Follow-up was completed for 144 patients (99.3 % of the cases). RESULTS: The hospital mortality rate was 1.4 %. There were no significant differences among Groups N, W and R in the freedom from valve-related death and cardiac death at 10 years after surgery. The rates of freedom from aorta-related events in the three groups at 10 years after surgery were 98.3 % (Group-N), 100 % (Group-W) and 100 % (Group-R). CONCLUSIONS: The long term survival was equivalent among the three groups, and the rates of freedom from aorta-related death or events were low. Our surgical protocol for the treatment of the enlarged ascending aorta associated with BAV is appropriate. PMID- 26563222 TI - Mortality Risk of Hypnotics: Strengths and Limits of Evidence. AB - Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p < 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival. PMID- 26563224 TI - Feasibility of neoadjuvant S-1 and oxaliplatin followed by surgery for resectable advanced gastric adenocarcinoma. AB - PURPOSE: In Japan, the administration of S-1 following D2 gastrectomy is a standard treatment for stage II/III gastric cancer (GC). However, the survival of stage IIIB/IIIC GC remains unsatisfactory. To improve this, we conducted a multicenter phase II study to evaluate the safety and efficacy of a neoadjuvant S 1 and oxaliplatin regimen (SOX) followed by surgery targeted at stage III GC. METHODS: Oxaliplatin was administered intravenously (130 mg/m(2)) on day 1, and S 1 was administered orally (40 mg/m(2), twice a day) for 14 days followed by a seven-day rest period. After three cycles of therapy, D2 gastrectomy was performed. RESULTS: A total of 14 patients were enrolled and completed the protocol treatment. Grade 3/4 toxicities included thrombocytopenia (21.4 %), anorexia (14.3 %), and diarrhea (7.1 %). Seven patients (50 %) underwent total gastrectomy, and seven patients underwent distal gastrectomy. Grade 3/4 surgical complications included pancreatic fistula (21.4 %) and lung infection (7.1 %). The pathological response rate was 85.7 %. CONCLUSION: Although our data are limited and preliminary, neoadjuvant SOX followed by surgery can be performed safely with a high pathological response rate in patients with resectable advanced GC. Further investigation of this neoadjuvant approach is warranted. PMID- 26563225 TI - Strategy for thoracic endovascular aortic repair based on collateral circulation to the artery of Adamkiewicz. AB - PURPOSE: Spinal cord ischemia (SCI) is a serious complication of thoracic endovascular aortic repair (TEVAR). The purpose of this study was to establish if preoperative identification of the artery of Adamkiewicz (AKA) can help prevent post-TEVAR SCI. METHODS: Of 74 post-TEVAR patients, 51 had the critical segmental artery (CSA) to the AKA pre-identified to help the surgeon deploy stent grafts. RESULTS: None of these 51 patients suffered permanent paraplegia postoperatively, but 5 (23.8 %) of the remaining 23 patients (2 of whom had pre-existing paraplegia) did suffer permanent SCI. The CSA/AKA was preserved in 43 patients with pre-identification of the CSA/AKA; however, in 8 patients, the CSA was completely or partially occluded by a stent graft. Transient SCI developed in one patient from each group, but both of these patients recovered fully before discharge. No change in the anatomical route was identified in 29 of the patients who had postoperative evaluation of the CSA/AKA. Five of eight patients whose CSA was completely occluded had new collateral circulation to the AKA. CONCLUSIONS: None of the 51 patients with the CSA/AKA identified before TEVAR suffered permanent paraplegia, whereas 5 of the 23 without pre-identification did suffer permanent SCI. Thus, careful identification of the CSA/AKA may prove useful for preventing postoperative SCI. Preservation of potential collateral circulation may also reduce the risk of postoperative SCI. PMID- 26563226 TI - Single-incision totally extraperitoneal inguinal hernia repair as a teaching procedure: one center's experience of more than 300 procedures. AB - PURPOSE: To evaluate resident doctors' proficiency in performing single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS TEP), and assess patient outcomes by comparing procedures performed by resident surgeons vs. those performed by staff surgeons. METHODS: We analyzed retrospectively 301 patients who underwent SILS-TEP between January 2011 and May 2015 at Osaka Police Hospital. RESULTS: The mean operative times for unilateral and bilateral hernia repairs in the resident-surgeon and the staff-surgeon groups were 99 vs. 88 min, respectively (p < 0.05), and 130 vs. 137 min, respectively. There was no significant difference in the incidence of conversion to a different procedure between the groups. The mean postoperative hospital stay was 2.0 days for patients from the resident-surgeon group vs. 2.8 days for those from the staff-surgeon group (p < 0.05). Seromas and wound infections developed in 8 % (12/148) of patients from the resident-surgeon group vs. 12 % (19/153) of those from the staff-surgeon group. No other major complications or hernia recurrence were noted in either group. CONCLUSIONS: SILS-TEP was performed safely, with low morbidity and no recurrence, by the resident surgeons under appropriate guidance by staff surgeons. PMID- 26563227 TI - Quantum Dot-Based Luminescent Oxygen Channeling Assay for Potential Application in Homogeneous Bioassays. AB - The unique photoproperties of quantum dots are promising for potential application in bioassays. In the present study, quantum dots were applied to a luminescent oxygen channeling assay. The reaction system developed in this study was based on interaction of biotin with streptavidin. Carboxyl-modified polystyrene microspheres doped with quantum dots were biotinylated and used as acceptors. Photosensitizer-doped carboxyl-modified polystyrene microspheres were conjugated with streptavidin and used as donors. The results indicated that the singlet oxygen that was released from the donor beads diffused into the acceptor beads. The acceptor beads were then exited via thioxene, and were subsequently fluoresced. To avoid generating false positives, a high concentration (0.01 mg/mL) of quantum dots is required for application in homogeneous immunoassays. Compared to a conventional luminescent oxygen channeling assay, this quantum dots based technique requires less time, and would be easier to automate and miniaturize because it requires no washing to remove excess labels. PMID- 26563228 TI - Prediction of Protein-Protein Interaction Sites with Machine-Learning-Based Data Cleaning and Post-Filtering Procedures. AB - Accurately predicting protein-protein interaction sites (PPIs) is currently a hot topic because it has been demonstrated to be very useful for understanding disease mechanisms and designing drugs. Machine-learning-based computational approaches have been broadly utilized and demonstrated to be useful for PPI prediction. However, directly applying traditional machine learning algorithms, which often assume that samples in different classes are balanced, often leads to poor performance because of the severe class imbalance that exists in the PPI prediction problem. In this study, we propose a novel method for improving PPI prediction performance by relieving the severity of class imbalance using a data cleaning procedure and reducing predicted false positives with a post-filtering procedure: First, a machine-learning-based data-cleaning procedure is applied to remove those marginal targets, which may potentially have a negative effect on training a model with a clear classification boundary, from the majority samples to relieve the severity of class imbalance in the original training dataset; then, a prediction model is trained on the cleaned dataset; finally, an effective post-filtering procedure is further used to reduce potential false positive predictions. Stringent cross-validation and independent validation tests on benchmark datasets demonstrated the efficacy of the proposed method, which exhibits highly competitive performance compared with existing state-of-the-art sequence-based PPIs predictors and should supplement existing PPI prediction methods. PMID- 26563229 TI - Anxiety Disorder-Specific Predictors of Treatment Outcome in the Coordinated Anxiety Learning and Management (CALM) Trial. AB - Identifying baseline characteristics associated with treatment outcome in generalized anxiety disorder, panic disorder, social anxiety disorder (SAD) or post-traumatic stress disorder. We performed two secondary analyses of the Coordinated Anxiety Learning and Management trial. Baseline characteristics and their interactions with treatment assignment were analyzed via stepwise logistic regression models and receiver-operating criterion analyses by disorder predicting remission and response for each disorder. Predictors for poor outcome across diagnoses were comorbid depression and low socioeconomic status. Good outcome was associated with positive treatment expectancy and high self-efficacy expectancy. SAD had the lowest rate of remission and response compared to the other anxiety disorders, and differed in respect to its predictors of treatment outcome. Perceived social support predicted treatment outcome in SAD. The special role of SAD among the other anxiety disorders requires further study both because of its worse prognosis and its more specific treatment needs. PMID- 26563230 TI - Distribution of pathogenicity island markers in commensal and uropathogenic Escherichia coli isolates. AB - Uropathogenic Escherichia coli (UPEC) isolates contain large genomic segments, termed pathogenicity islands (PAIs), that contribute to their virulence. A total of 150 UPEC and 50 commensal E. coli isolates from outpatients were investigated for antimicrobial susceptibility and the presence of eight PAI markers. One hundred ninety (95 %) isolates were resistant to one or more antimicrobial agents. The most frequent resistance found against amoxicillin (68 %), amoxicillin/clavulanic acid (55 %), aztreonam (50 %), trimethoprim/sulfamethoxazole (46 %) and tetracycline (43.5 %). Antimicrobial resistance among UPEC isolates was higher than that of commensals. PAI markers were detected in substantial percentage of commensal (88 %) and UPEC isolates (98.6 %) (P > 0.05). The most prevalent PAI marker among UPEC and commensal isolates was PAI IV536 (98.7 % UPEC vs. 84 % commensal). We found a high number of PAI markers such as PAI ICFT073, PAI IICFT073, PAI I536, PAI II536, PAI III536 and PAI IIJ96 significantly associated with UPEC. PAI III536 (21.3 %) and PAI IIJ96 (8 %) were detected only in the uropathogenic isolates. Several different combinations of PAIs were found among UPEC isolates. Comparison of PAIs among UPEC and commensal isolates showed that many UPEC isolates (79.3 %) carried two or more PAI markers, while 6 % of commensals had two PAI markers (P < 0.05). The most frequent combinations of PAI markers in UPEC isolates were PAI IV536 + PAI IICFT073 (18 %) and PAI IV536 + PAI ICFT073 + PAI IICFT073 (18 %). These results indicate that PAI markers are widespread among commensal and UPEC isolates and these commensal isolates may be reservoirs for transmission of these markers. PMID- 26563232 TI - Mitigation measures to contain the environmental impact of urban areas: a bibliographic review moving from the life cycle approach. AB - The global environmental impact of urban areas has greatly increased over the years, due to the growth of urbanisation and the associated increase in management costs. There are several measures aimed at mitigating this impact that affect in different ways the environmental, economic and societal spheres. This article has analysed a selection of different mitigation measures, related to the built environment, according to the life cycle approach, aimed at identifying the procedural features chosen by the different authors and defining a common way to deal with this issue. In particular, all the individual single steps of a Life Cycle Assessment/Life Cycle Costing of the different studies are analysed and the results of the individual measures are highlighted. The analysis has shown how the scientific literature is mainly focused on the evaluation of the impact of technological solutions related to individual buildings (cool/green roof). Less interest is shown in the solutions for urban areas, while, as far as the impact on greenhouse gas emissions is concerned, some studies are shifting the target to a global scale. Due to the accuracy whereby the calculation of the impact indicators deals with and structures the life cycle methods, opportunities to compare studies developed by different authors are quite rare and hard to find. Hence the need to find a simple, intuitive and flexible scheme to combine some of the most useful results of the bibliographical studies, in a comparative outline of different technological solutions, which can support the decision-making phase through a rough assessment. PMID- 26563231 TI - Biological index of environmental lead pollution: accumulation of lead in liver and kidney in mice. AB - Lead (Pb) is known to be highly poisonous, and the acute poisoning of Cd causes the abdominal pains, vomiting, and shock. The digestive and nervous symptom is observed in the chronic lead poisoning. It was also known that the defect in hemoglobin synthesis by Pb produce anemia. The release of Pb into the environment presents a source of exposure for wild animals. In this study, we examined the utility of a new Pb-monitoring index in mice administered Pb. A solution containing 0.02, 0.2, 2, or 4 ppm lead chloride (PbCl2) was administered intraperitoneally to mice, and the Pb contents of the kidney and liver were determined at designated time points. The mean Pb content of both organs increased depending on the administered Pb dosage. Although the results of control was near the detection limits, the administration of 4 ppm in 4 weeks resulted in Pb levels of 260 mg ppm/wet weight and 110 ppm wet weight in the kidney and liver, respectively. However, there were no significant relationships among administered dose, duration of Pb treatment, and liver or kidney Pb content. Then, values in all mice administered control or 0.02 mg Pb were located inside the ellipse, representing the confidence area of the new index, and values in all mice administered more than 2 mg Pb were located outside the ellipse. These results confirm that animals exposed to high concentrations of Pb would be detected by this new index. PMID- 26563233 TI - Modelling the regional variability of the probability of high trihalomethane occurrence in municipal drinking water. AB - The regional variability of the probability of occurrence of high total trihalomethane (TTHM) levels was assessed using multilevel logistic regression models that incorporate environmental and infrastructure characteristics. The models were structured in a three-level hierarchical configuration: samples (first level), drinking water utilities (DWUs, second level) and natural regions, an ecological hierarchical division from the Quebec ecological framework of reference (third level). They considered six independent variables: precipitation, temperature, source type, seasons, treatment type and pH. The average probability of TTHM concentrations exceeding the targeted threshold was 18.1%. The probability was influenced by seasons, treatment type, precipitations and temperature. The variance at all levels was significant, showing that the probability of TTHM concentrations exceeding the threshold is most likely to be similar if located within the same DWU and within the same natural region. However, most of the variance initially attributed to natural regions was explained by treatment types and clarified by spatial aggregation on treatment types. Nevertheless, even after controlling for treatment type, there was still significant regional variability of the probability of TTHM concentrations exceeding the threshold. Regional variability was particularly important for DWUs using chlorination alone since they lack the appropriate treatment required to reduce the amount of natural organic matter (NOM) in source water prior to disinfection. Results presented herein could be of interest to authorities in identifying regions with specific needs regarding drinking water quality and for epidemiological studies identifying geographical variations in population exposure to disinfection by-products (DBPs). PMID- 26563234 TI - Environmental quality assessment of Grand Harbour (Valletta, Maltese Islands): a case study of a busy harbour in the Central Mediterranean Sea. AB - Contamination levels by plastic debris, trace elements and persistent organic pollutants were assessed and related to macrobenthic diversity within soft bottoms of Grand Harbour (Malta, Central Mediterranean). Sediment toxicity was evaluated by ecotoxicological method, deploying Bacteria (Vibrio fischeri), Echinodermata (Paracentrotus lividus) and Crustacea (Corophium orientale). Univariate analysis (Pearson's test) was used to test relationships between biodiversity indices, pollutants and grain size. A multivariate approach (PERMANOVA) was applied to investigate for any significant differences among sampling stations concerning plastic abundances and to test the relationship between infaunal abundances and pollutant concentrations (the BIOENV test). Significant differences in the plastic abundances were found between sampling stations. The lowest value for Shannon-Wiener biodiversity index was associated to the highest sediment pollution level. Multivariate analyses suggest that MBT and TBT were factors that most influenced macrozoobenthic abundance and biodiversity. The bivalve Corbula gibba and the introduced polychaete Monticellina dorsobranchialis were the most abundant found species. PMID- 26563235 TI - Assessment by self-organizing maps of element release from sediments in contact with acidified seawater in laboratory leaching test conditions. AB - Carbon capture and storage (CCS) is gaining interest as a significant global option to reduce emissions of CO2. CCS development requires an assessment of the potential risks associated with CO2 leakages from storage sites. Laboratory leaching tests have proved to be a useful tool to study the potential mobilization of metals from contaminated sediment in a decreased-pH environment that mimics such a leakage event. This work employs a self-organizing map (SOM) tool to interpret and analyze the release of dissolved organic carbon (DOC), As, Cd, Cr, Cu, Ni, Pb, and Zn from equilibrium, column, and pH-dependent leaching tests. In these tests, acidified seawater is used for simulating different CO2 leakage scenarios. Classification was carried out detailing the mobilization of contaminants for environments of varying pH, liquid-to-solid ratio, and type of contact of the laboratory leaching tests. Component planes in the SOMs allow visualization of the results and the determination of the worst case of element release. The pH-dependent leaching test with initial addition of either base or acid was found to mobilize the highest concentrations of metals. PMID- 26563236 TI - Bridging the Sciences of Mindfulness and Romantic Relationships. AB - Research on mindfulness, defined as paying conscious and non-judgmental attention to present-moment experiences, has increased rapidly in the past decade but has focused almost entirely on the benefits of mindfulness for individual well-being. This article considers the role of mindfulness in romantic relationships. Although strong claims have been made about the potentially powerful role of mindfulness in creating better relationships, it is less clear whether, when, and how this may occur. This article integrates the literatures on mindfulness and romantic relationship science, and sketches a theory-driven model and future research agenda to test possible pathways of when and how mindfulness may affect romantic relationship functioning. We review some initial direct and indirect evidence relevant to the proposed model. Finally, we discuss the implications of how studying mindfulness may further our understanding of romantic relationship (dys)functioning, and how mindfulness may be a promising and effective tool in couple interventions. PMID- 26563237 TI - Pneumococcal Infection Aggravates Elastase-Induced Emphysema via Matrix Metalloproteinase 12 Overexpression. AB - BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD)- typically caused by bacterial or viral infection--is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. METHODS: We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. RESULTS: In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, an increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly owing to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and emphysema progression. CONCLUSIONS: These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD. PMID- 26563238 TI - Important Complexities of the Antivirulence Target Paradigm: A Novel Ostensibly Resistance-Avoiding Approach for Treating Infections. AB - Use of antivirulence therapy has assumed that inhibition of bacterial fitness at the site of infection without directly affecting viability will minimize the development of resistance. However, selection for resistant strains is much more likely to occur at sites of colonization or in the environment following excretion of the therapeutic agent. Data are needed regarding whether the drug's target promotes fitness among bacteria in (drug-exposed) niches other than sites of infection. Furthermore, in vivo studies of resistance selection should assess off-target selection for resistance (eg, within the microbiome). Only when such data are available can the risk for development of resistance be gauged appropriately. PMID- 26563239 TI - Stability of a Vesicular Stomatitis Virus-Vectored Ebola Vaccine. AB - The live attenuated vesicular stomatitis virus-vectored Ebola vaccine rVSV-ZEBOV is currently undergoing clinical trials in West Africa. The vaccine is to be stored at -70 degrees C or less. Since maintaining the cold chain is challenging in rural areas, the rVSV-ZEBOV vaccine's short-term and long-term stability at different temperatures was examined. Different dilutions were tested since the optimal vaccine dosage had not yet been determined at the start of this experiment. The results demonstrate that the original vaccine formulation was stable for 1 week at 4 degrees C and for 24 hours at 25 degrees C. The stability of the vaccine was compromised by both high temperatures and dilution. PMID- 26563240 TI - Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA). AB - The injectable long-acting formulation of rilpivirine (TMC278LA) is a promising preexposure prophylaxis (PrEP) candidate for prevention of human immunodeficiency virus type 1 (HIV-1) infection. We evaluated HIV-1 in plasma obtained from an unexpected seroconverter in the 300-mg arm of the SSAT040 TMC278LA pharmacokinetic study for rilpivirine (RPV) resistance. Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma derived clones from the same individual. This case is a unique instance of infection with wild-type HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP. PMID- 26563241 TI - Amblyopia. PMID- 26563242 TI - Editorial Comment: New Directions in Orthopaedic Education. PMID- 26563243 TI - CORR Insights((r)): Transcriptional Profiling Identifies the Signaling Axes of IGF and Transforming Growth Factor-beta as Involved in the Pathogenesis of Osteosarcoma. PMID- 26563244 TI - Editorial Comment: 2014 Musculoskeletal Tumor Society. PMID- 26563245 TI - Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale. AB - Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of alpha1-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studies on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques. PMID- 26563246 TI - Critical features of peer assessment of clinical performance to enhance adherence to a low back pain guideline for physical therapists: a mixed methods design. AB - BACKGROUND: Clinical practice guidelines are intended to improve the process and outcomes of patient care. However, their implementation remains a challenge. We designed an implementation strategy, based on peer assessment (PA) focusing on barriers to change in physical therapy care. A previously published randomized controlled trial showed that PA was more effective than the usual strategy "case discussion" in improving adherence to a low back pain guideline. Peer assessment aims to enhance knowledge, communication, and hands-on clinical skills consistent with guideline recommendations. Participants observed and evaluated clinical performance on the spot in a role-play simulating clinical practice. Participants performed three roles: physical therapist, assessor, and patient. This study explored the critical features of the PA program that contributed to improved guideline adherence in the perception of participants. METHODS: Dutch physical therapists working in primary care (n = 49) organized in communities of practice (n = 6) participated in the PA program. By unpacking the program we identified three main tasks and eleven subtasks. After the program was finished, a questionnaire was administered in which participants were asked to rank the program tasks from high to low learning value and to describe their impact on performance improvement. Overall ranking results were calculated. Additional semi structured interviews were conducted to elaborate on the questionnaires results and were transcribed verbatim. Questionnaires comments and interview transcripts were analyzed using template analysis. RESULTS: Program tasks related to performance in the therapist role were perceived to have the highest impact on learning, although task perceptions varied from challenging to threatening. Perceptions were affected by the role-play format and the time schedule. Learning outcomes were awareness of performance, improved attitudes towards the guideline, and increased self-efficacy beliefs in managing patients with low back pain. Learning was facilitated by psychological safety and the quality of feedback. CONCLUSION: The effectiveness of PA can be attributed to the structured and performance-based design of the program. Participants showed a strong cognitive and emotional commitment to performing the physical therapist role. That might have contributed to an increased awareness of strength and weakness in clinical performance and a motivation to change routine practice. PMID- 26563247 TI - Activation of Wnt/beta-catenin signaling in ESC promotes rostral forebrain differentiation in vitro. AB - Wnt/beta-catenin signaling is crucial for maintenance of pluripotent state of embryonic stem cell (ESC). However, it is unclear how Wnt/beta-catenin signaling affects the differentiation ability of ESC, especially with regard to rostral forebrain cells. Here, using Rax, rostral forebrain marker, and Wnt/beta-catenin reporter lines, we report ratio of Rax(+) and Wnt responding tissue (Wnt(+)) patterns, which were affected by seeding number of ESC in three-dimensional culture system. Surprisingly, we found beta-catenin level and localization are heterogeneous in ESC colony by immunostaining and time-laps imaging of beta catenin-mEGFP signals. Moreover, activation of Wnt signaling in ESC promoted expression level and nuclear localization of beta-catenin, and mRNA levels of Wnt antagonists, axin2 and dkk1, leading to upregulating Wnt/beta-catenin reporter in ESC state and Rax expression at differentiation culture day 7. Together, our results suggest that activation of Wnt signaling in ESC promotes the differentiation efficacy of rostral forebrain cells. Wnt-priming culture method may provide a useful tool for applications in the areas of basic science and molecular therapeutics for regenerative medicine. PMID- 26563248 TI - Cost-Effectiveness Models in Age-Related Macular Degeneration: Issues and Challenges. AB - Age-related macular degeneration (AMD) is a common ophthalmic condition that can have few symptoms in its early stage but can progress to major visual impairment. While there are no treatments for early-stage AMD, there are multiple modalities of treatment for advanced disease. Given the increasing prevalence of the disease, there are dozens of analyses of cost effectiveness of AMD treatments, but methods and approaches vary broadly. The goal of this review was to identify, characterize, and critique published models in AMD and provide guidance for their interpretation. After a literature review was performed to identify studies, and exclusion criteria applied to limit the review to studies comparing treatments for AMD, we compared methods across the 36 studies meeting the review criteria. To some extent, variation was related to targeting different audiences or acknowledging the most appropriate population for a given treatment. However, the review identified potential areas of uncertainty and difficulty in interpretation, particularly regarding duration of observation periods and the importance of visual acuity as an endpoint or a proxy for patient-reported utilities. We urge thoughtful consideration of these study characteristics when comparing results. PMID- 26563249 TI - Measuring nonspecific factors in treatment: item banks that assess the healthcare experience and attitudes from the patient's perspective. AB - PURPOSE: Nonspecific factors that accompany healthcare treatments, such as patients' attitudes and expectations, are important parts of the experience of care and can influence outcomes. However, no precise, concise, and generalizable instruments to measure these factors exist. We report on the development and calibration of new item banks, titled the Healing Encounters and Attitudes Lists (HEAL), that assess nonspecific factors across a broad range of treatments and conditions. METHODS: The instrument development methodology of the Patient Reported Outcomes Measurement Information System (PROMIS((r))) was used. Patient focus groups and clinician interviews informed our HEAL conceptual model. Literature searches of eight databases yielded over 500 instruments and resulted in an initial item pool of several thousand items. After qualitative item analysis, including cognitive interviewing, 296 items were included in field testing. The calibration sample included 1657 respondents, 1400 obtained through an Internet panel and 257 from conventional and integrative medicine clinics. Following exploratory and confirmatory factor analyses, the HEAL item banks were calibrated using item response theory. RESULTS: The final HEAL item banks were Patient-Provider Connection (57 items), Healthcare Environment (25 items), Treatment Expectancy (27 items), Positive Outlook (27 items), and Spirituality (26 items). Short forms were also developed from each item bank. A six-item short form, Attitudes toward Complementary and Alternative Medicine (CAM), was also created. CONCLUSIONS: HEAL item banks provided substantial information across a broad range of each construct. HEAL item banks showed initial evidence of predictive and concurrent validity, suggesting that they are suitable for measuring nonspecific factors in treatment. PMID- 26563250 TI - Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy. AB - PURPOSE: It is well known that a significant proportion of heart failure patients (10-44 %) do not show improvement in symptoms or functioning from cardiac resynchronization therapy (CRT), yet no study has examined patient-reported health status trajectories after implantation. METHODS: A cohort of 139 patients with a CRT-defibrillator (70 % men; age 65.7 +/- 10.1 years) completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) prior to implantation (baseline) and at 2, 6, and 12-14 months post-implantation. Latent class analyses were used to identify trajectories and associates of disease-specific health status over time. RESULTS: All health status trajectories showed an initial small to large improvement from baseline to 2-month follow-up, whereafter most trajectories displayed a stable pattern between short- and long-term follow-up. Low educational level, NYHA class III/IV, smoking, no use of beta-blockers, use of psychotropic medication, anxiety, depression, and type D personality were found to be associated with poorer health status in unadjusted analyses. Interestingly, subgroups of patients (12-20 %) who experienced poor health status at baseline improved to stable good health status levels after implantation. CONCLUSIONS: Levels of disease-specific health status vary considerably across subgroups of CRT-D patients. Classification into poorer disease-specific health status trajectories was particularly associated with patients' psychological profile and NYHA classification. The timely identification of CRT-D patients who present with poor disease-specific health status (i.e., KCCQ score < 50) and a distressed psychological profile (i.e., anxiety, depression, and/or type D personality) is paramount, as they may benefit from cardiac rehabilitation in combination with psychological intervention. PMID- 26563251 TI - Patient-reported outcomes: pathways to better health, better services, and better societies. AB - While the use of PROs in research is well established, many challenges lie ahead as their use is extended to other applications. There is consensus that health outcome evaluations that include PROs along with clinician-reported outcomes and administrative data are necessary to inform clinical and policy decisions. The initiatives presented in this paper underline evolving recognition that PROs play a unique role in adding the patient perspective alongside clinical (e.g., blood pressure) and organizational (e.g., admission rates) indicators for evaluating the effects of new products, selecting treatments, evaluating quality of care, and monitoring the health of the population. In this paper, we first explore the use of PRO measures to support drug approval and labeling claims. We critically evaluate the evidence and challenges associated with using PRO measures to improve healthcare delivery at individual and population levels. We further discuss the challenges associated with selecting from the abundance of measures available, opportunities afforded by agreeing on common metrics for constructs of interest, and the importance of establishing an evidence base that supports integrating PRO measures across the healthcare system to improve outcomes. We conclude that the integration of PROs as a key end point within individual patient care, healthcare organization and program performance evaluations, and population surveillance will be essential for evaluating whether increased healthcare expenditure is translating into better health outcomes. PMID- 26563252 TI - Are Synonymous Sites in Primates and Rodents Functionally Constrained? AB - It has been claimed that synonymous sites in mammals are under selective constraint. Furthermore, in many studies the selective constraint at such sites in primates was claimed to be more stringent than that in rodents. Given the larger effective population sizes in rodents than in primates, the theoretical expectation is that selection in rodents would be more effective than that in primates. To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. To further control for shifts in GC content, we estimated selective constraint at fourfold degenerate sites using a maximum parsimony approach. This allowed us to estimate selective constraint using mutational patterns that cause a shift in GC content (GT <-> TG, CT <-> TC, GA <-> AG, and CA <-> AC) and ones that do not (AT <-> TA and CG <-> GC). Using this approach, we found that synonymous sites evolve neutrally in both primates and rodents. Apparent deviations from neutrality were caused by a higher rate of C -> A and C > T mutations in pseudogenes. Such differences are most likely caused by the shift in GC content experienced by pseudogenes. We conclude that previous estimates according to which 20-40% of synonymous sites in primates were under selective constraint were most likely artifacts of the biased pattern of mutation. PMID- 26563253 TI - Preparation and Evaluation of Phospholipid-Based Complex of Standardized Centella Extract (SCE) for the Enhanced Delivery of Phytoconstituents. AB - In the present study, a phospholipid-based complex of standardized Centella extract (SCE) was developed with a goal of improving the bioavailability of its phytoconstituents. The SCE-phospholipid complex was prepared by solvent evaporation method and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy, and powder x-ray diffraction (PXRD) were used to confirm the formation of Centella naturosome (CN). The prepared complex was functionally evaluated by apparent solubility, in vitro drug release, ex vivo permeation, and in vivo efficacy studies. The prepared CN exhibited a significantly higher (12-fold) aqueous solubility (98.0 +/- 1.4 MUg/mL), compared to the pure SCE (8.12 +/- 0.44 MUg/mL), or the physical mixture of SCE and the phospholipid (13.6 +/- 0.4 MUg/mL). The in vitro dissolution studies revealed a significantly higher efficiency of CN in releasing the SCE (99.2 +/- 4.7, % w/w) in comparison to the pure SCE (39.2 +/- 2.3, % w/w), or the physical mixture (42.8 +/- 2.09, % w/w). The ex vivo permeation studies with the everted intestine method showed that the prepared CN significantly improved the permeation of SCE (82.8 +/- 3.7, % w/w), compared to the pure SCE (26.8 +/- 2.4, % w/w), or the physical mixture (33.0 +/- 2.7, % w/w). The in vivo efficacy studies using the Morris Water Maze test indicated a significant improvement of the spatial learning and memory in aged mice treated with CN. Thus, drug-phospholipid complexation appears to be a promising strategy to improve the aqueous solubility and bioavailability of bioactive phytoconstituents. PMID- 26563254 TI - Measles among migrants in the European Union and the European Economic Area. AB - AIMS: Progress towards meeting the goal of measles elimination in the EU and the European Economic Area (EEA) by 2015 is being obstructed, as some children are either not immunized on time or never immunized. One group thought to be at increased risk of measles is migrants; however, the extent to which this is the case is poorly understood, due to a lack of data. This paper addresses this evidence gap by providing an overview of the burden of measles in migrant populations in the EU/EEA. METHODS: Data were collected through a comprehensive literature review, a country survey of EU/EEA member states and information from measles experts gathered at an infectious disease workshop. RESULTS: Our results showed incomplete data on measles in migrant populations, as national surveillance systems do not systematically record migration-specific information; however, evidence from the literature review and country survey suggested that some measles outbreaks in the EU/EEA were due to sub-optimal vaccination coverage in migrant populations. CONCLUSIONS: We conclude that it is essential that routine surveillance of measles cases and measles, mumps and rubella (MMR) vaccination coverage become strengthened, to capture migrant-specific data. These data can help to inform the provision of preventive services, which may need to reach out to vulnerable migrant populations that currently face barriers in accessing routine immunization and health services. PMID- 26563255 TI - Prevention of infection-related cancers in the WHO Western Pacific Region. AB - A considerable number of infectious agents have been classified as human carcinogens Group 1 by the International Agency for Research on Cancer. Major infection-related cancers such as cancers of nasopharynx (53%), stomach (60%) and liver (63%) occur in the World Health Organization Western Pacific Region. Many infection-related cancers are preventable, particularly those associated with human papilloma virus, Helicobacter pylori, human immunodeficiency virus-I, hepatitis B virus and hepatitis C virus and liver flukes. Mongolia shows the highest prevalence of hepatitis B virus and hepatitis C virus, and China shows the highest prevalence of Helicobacter pylori. Chronic infection is attributable for 17-28% of overall cancer incidence or mortality in China, Japan and Korea. Through infant immunization for hepatitis B, 30 of 37 countries and areas in the Western Pacific Region have reached the 2012 milestone of chronic hepatitis B virus infection prevalence of <2% in 5-year-old children and countries and areas of the region are now striving toward reaching the regional goal of <1% by 2017. Human papilloma virus immunization program is implemented either by government funding or, in some low-income countries, by public and private sector organizations. Cervical cancer screening via visual inspection with acetic acid or Pap smear is available in many Western Pacific Region Member States. More efforts are needed to implement new World Health Organization guide to vaccinate 9- to 13-year-old girls with two doses of human papilloma virus vaccine, and use human papilloma virus tests to screen women to prevent and control cervical cancer including guaranteed monitoring and appropriate follow-up for abnormal results. PMID- 26563256 TI - Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS). AB - Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data. PMID- 26563257 TI - A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin-docetaxel with or without trastuzumab in locally advanced breast cancer. AB - PURPOSE: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with and without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC). METHODS: Eighty patients with LABC (T2-T4, N0-N2, M0) were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin and docetaxel, plus trastuzumab if HER2 positive. The primary endpoint was pathologic complete response (pCR) in breast and axilla in separate HER2-negative and HER2-positive cohort. RESULTS: Eighty patients were evaluable for analysis of which 51 were HER2 negative and 29 HER2 positive: median age: 43 years, premenopausal: 82%, median tumor size: 7.0 cm (4-10), stage IIB: 25% and IIIA/IIIB: 75%, both ER/PR positive: 56%, HER2 positive (3+) by IHC staining: 36%. Clinical complete response was seen in 48%, and clinical partial response was seen in 52%. Overall the pathologic complete response (pCR) was 36% in breast, 64 % in axilla, and 32% in both breast and axilla. Analysis of pCR in breast and axilla, as a function of the hormonal receptor (HR) and HER2, was as follows: HR(+)/HER2(-): 11%; HR(+)/HER(+): 56 %; HR(-)/HER2(-): 36%; HR( )/HER2(+): 62%. CONCLUSION: In this series of locally advanced breast cancer, the combination of (FEC100) followed by cisplatin/docetaxel with and without trastuzumab was very active obtaining an impressive rate of pCR, particularly in HER2-positive and triple negative disease, which merits further investigation. PMID- 26563258 TI - Antimitotic drugs in the treatment of cancer. AB - Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell resistance to chemotherapy and other limitations of current antimitotic compounds are highlighted, as well as the potential of novel 17-beta estradiol analogs as cancer treatment. PMID- 26563259 TI - Diagnosis and management of menopause: summary of NICE guidance. PMID- 26563261 TI - Varenicline and Suicide: Reconsidered and Reconciled. PMID- 26563260 TI - Fine-grained information extraction from German transthoracic echocardiography reports. AB - BACKGROUND: Information extraction techniques that get structured representations out of unstructured data make a large amount of clinically relevant information about patients accessible for semantic applications. These methods typically rely on standardized terminologies that guide this process. Many languages and clinical domains, however, lack appropriate resources and tools, as well as evaluations of their applications, especially if detailed conceptualizations of the domain are required. For instance, German transthoracic echocardiography reports have not been targeted sufficiently before, despite of their importance for clinical trials. This work therefore aimed at development and evaluation of an information extraction component with a fine-grained terminology that enables to recognize almost all relevant information stated in German transthoracic echocardiography reports at the University Hospital of Wurzburg. METHODS: A domain expert validated and iteratively refined an automatically inferred base terminology. The terminology was used by an ontology-driven information extraction system that outputs attribute value pairs. The final component has been mapped to the central elements of a standardized terminology, and it has been evaluated according to documents with different layouts. RESULTS: The final system achieved state-of-the-art precision (micro average.996) and recall (micro average.961) on 100 test documents that represent more than 90 % of all reports. In particular, principal aspects as defined in a standardized external terminology were recognized with f 1=.989 (micro average) and f 1=.963 (macro average). As a result of keyword matching and restraint concept extraction, the system obtained high precision also on unstructured or exceptionally short documents, and documents with uncommon layout. CONCLUSIONS: The developed terminology and the proposed information extraction system allow to extract fine grained information from German semi-structured transthoracic echocardiography reports with very high precision and high recall on the majority of documents at the University Hospital of Wurzburg. Extracted results populate a clinical data warehouse which supports clinical research. PMID- 26563262 TI - Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach. AB - INTRODUCTION: Electronic cigarette (ECIG) use has grown rapidly in popularity within a short period of time. As ECIG products continue to evolve and more individuals begin using ECIGs, it is important to understand the potential adverse effects that are associated with ECIG use. The purpose of this study was to examine and describe the acute adverse effects associated with ECIG use. METHODS: This study used an integrated, mixed-method participatory approach called concept mapping (CM). Experienced ECIG users (n = 85) provided statements that answered the focus prompt "A specific negative or unpleasant effect (ie, physical or psychological) that I have experienced either during or immediately after using an electronic cigarette device is..." in an online program. Participants sorted these statements into piles of common themes and rated each statement. Using multidimensional scaling and hierarchical cluster analysis, a concept map of the adverse effects statements was created. RESULTS: Participants generated 79 statements that completed the focus prompt and were retained by researchers. Analysis generated a map containing five clusters that characterized perceived adverse effects of ECIG use: Stigma, Worry/Guilt, Addiction Signs, Physical Effects, and Device/Vapor Problems. CONCLUSIONS: ECIG use is associated with adverse effects that should be monitored as ECIGs continue to grow in popularity. If ECIGs are to be regulated, policies should be created that minimize the likelihood of user identified adverse effects. IMPLICATIONS: This article provides a list of adverse effects reported by experienced ECIG users. This article organizes these effects into a conceptual model that may be useful for better understanding the adverse outcomes associated with ECIG use. These identified adverse effects may be useful for health professionals and policy makers. Health professionals should be aware of potential negative health effects that may be associated with ECIG use and policy makers could design ECIG regulations that minimize the risk of the adverse effects reported by ECIG users in this study. PMID- 26563263 TI - Reversion of malignant phenotypes of human glioblastoma cells by beta-elemene through beta-catenin-mediated regulation of stemness-, differentiation- and epithelial-to-mesenchymal transition-related molecules. AB - BACKGROUND: Glioblastoma is the most common and lethal type of primary brain tumor. beta-Elemene, a natural plant drug extracted from Curcuma wenyujin, has shown strong anti-tumor effects in various tumors with low toxicity. However, the effects of beta-elemene on malignant phenotypes of human glioblastoma cells remain to be elucidated. Here we evaluated the effects of beta-elemene on cell proliferation, survival, stemness, differentiation and the epithelial-to mesenchymal transition (EMT) in vitro and in vivo, and investigated the mechanisms underlying these effects. METHODS: Human primary and U87 glioblastoma cells were treated with beta-elemene, cell viability was measured using a cell counting kit-8 assay, and treated cells were evaluated by flow cytometry. Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors. Transwell assays were performed to further determine EMT of glioblastoma cells. To evaluate the effect of beta-elemene on glioblastoma in vivo, we subcutaneously injected glioblastoma cells into the flank of nude mice and then intraperitoneally injected NaCl or beta-elemene. The tumor xenograft volumes were measured every 3 days and the expression of stemness-, differentiation- and EMT-related effectors was determined by Western blot assays in xenografts. RESULTS: beta-Elemene inhibited proliferation, promoted apoptosis, impaired invasiveness in glioblastoma cells and suppressed the growth of animal xenografts. The expression levels of the stemness markers CD133 and ATP-binding cassette subfamily G member 2 as well as the mesenchymal markers N-cadherin and beta-catenin were significantly downregulated, whereas the expression levels of the differentiation related effectors glial fibrillary acidic protein, Notch1, and sonic hedgehog as well as the epithelial marker E-cadherin were upregulated by beta-elemene in vitro and in vivo. Interestingly, the expression of vimentin was increased by beta-elemene in vitro; this result was opposite that for the in vivo procedure. Inhibiting beta-catenin enhanced the anti-proliferative, EMT-inhibitory and specific marker expression-regulatory effects of beta-elemene. CONCLUSIONS: beta Elemene reversed malignant phenotypes of human glioblastoma cells through beta catenin-involved regulation of stemness-, differentiation- and EMT-related molecules. beta-Elemene represents a potentially valuable agent for glioblastoma therapy. PMID- 26563265 TI - In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography. AB - One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (u raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, u raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma diagnosis with higher accuracy than in vivo HD-OCT analysis of morphology alone. PMID- 26563266 TI - Effect of Ag Templates on the Formation of Au-Ag Hollow/Core-Shell Nanostructures. AB - Au-Ag alloy nanostructures with various shapes were synthesized using a successive reduction method in this study. By means of galvanic replacement, twined Ag nanoparticles (NPs) and single-crystalline Ag nanowires (NWs) were adopted as templates, respectively, and alloyed with the same amount of Au(+) ions. High angle annular dark field-scanning TEM (HAADF-STEM) images observed from different rotation angles confirm that Ag NPs turned into AuAg alloy rings with an Au/Ag ratio of 1. The shifts of surface plasmon resonance and chemical composition reveal the evolution of the alloy ring formation. On the other hand, single-crystalline Ag NWs became Ag@AuAg core-shell wires instead of hollow nanostructure through a process of galvanic replacement. It is proposed that in addition to the ratio of Ag templates and Au ion additives, the twin boundaries of the Ag templates were the dominating factor causing hollow alloy nanostructures. PMID- 26563267 TI - Neurosurgical education in Europe. PMID- 26563268 TI - Trends in Evidence-Based Lifestyle Interventions Directed at Obese and Overweight Adult Latinos in the US: A Systematic Review of the Literature. AB - The increasing prevalence of obesity in the United States (US) is well documented and presents a significant challenge for healthcare providers working with under resourced communities that often face great obstacles to health-related weight loss. Specifically, it has been reported that obesity disproportionately affects US Latino communities. Yet, little is known about what obesity lifestyle interventions currently exist. Healthcare professionals working in predominantly Latino communities might be interested in learning about the designs and outcomes of existing lifestyle interventions that have been specifically tailored for Latino communities. Here, we report the results of a systematic review of obesity lifestyle interventions targeting Latino adults. We examine the designs and outcomes of the nine articles that met our inclusion criteria. All the studies had physical activity and/or nutritional education components, measurements of both crude weight loss and body mass index (BMI), and some used culturally relevant intervention designs. Two of the nine studies reported significant between-group differences in BMI. Significant barriers between studies include small sample size, low retention rate, enrollment, low adherence, differences in control group activities, and differences in outcomes measured. We recommend that future obesity interventions select and report BMI, raw weight, and body fat percentage as outcome variables and that multiple measurements over multiple days be recorded for pre- and post-intervention data points. PMID- 26563269 TI - Effect of selective anthelmintic treatments on health and production parameters in Pelibuey ewes during lactation. AB - A study was conducted from December to April 2013, with the aim of evaluating a system of selective antiparasitic treatments using the FAMACHA(c) color chart compared with a conventional suppressive deworming system every 30 days in Pelibuey ewes during lactation. For the study, 54 ewes were used. They were randomly divided into two groups: FAMACHA and chemical treatments. The ewes in the first group received selective treatment depending on the ocular mucosa coloration (FAMACHA) and body condition score (BCS), while in the second group (chemical) all the animals remained under routine deworming every 30 days. Fecal nematode egg counts, proportion of third-stage trichostrongylid larvae, body condition, coloration of the ocular mucosa, and packed cell volume in the ewes were determined, while in lambs only body weight (BW) was recorded. No significant differences (p > 0.05) were observed in any of the studied variables between groups; however, the use of antiparasitic drugs was reduced during the experimental period in the FAMACHA group and no deaths of lambs or ewes were recorded. The results indicate that during the lactation of ewes, a strategy of selective treatments can be implemented without showing deterioration in major health and productive parameters of these animals. PMID- 26563270 TI - Quantitative analysis of risk factors associated with brucellosis in livestock in the Katavi-Rukwa ecosystem, Tanzania. AB - Brucellosis is a neglected contagious bacterial disease of public health and economic importance. Nevertheless, its spread is not well known to many livestock farmers. Unmatched case control study was carried out to identify risk factors associated with brucellosis in cattle and goats at the herd level in Mpanda, Mlele and Nsimbo districts of Katavi region, in Tanzania between September 2012 and July 2013. A total of 138 adult respondents were selected randomly for the interview using a structured questionnaire. The criterion for inclusion was to have at least one Brucella-positive animal in the herd while the control was chosen from among the herds which these animals tested negative. The presence of seropositive herds were statistically linked (P < 0.1) by univariate analysis with such variables as lack of formal education among the herders; slaughtering of cattle or goats in the household; the history of occurrence of abortion in the herd; and the history of occurrence of retained foetal membranes in the herd following parturition. However, in the multivariate analysis, lack of formal education among the herders and the previous history of occurrence of retained foetal membrane in the herd following parturition were significantly associated with Brucella seropositive (P < 0.05). This study suggests the need for raising community awareness on the risk factors associated with the transmission of brucellosis between animals and humans and the implementation of disease prevention and control programmes. PMID- 26563271 TI - Sero-positivity and associated risk factors for contagious bovine pleuropneumonia under two cattle production systems in North Central Nigeria. AB - A cross-sectional survey of 765 cattle in 125 nomadic and 375 cattle in 125 sedentary herds was conducted to investigate prevalence and risk factors for contagious bovine pleuropneumonia (CBPP) in the two production systems of Niger State in North Central Nigeria, between January and August 2013. Data on herd characteristics were collected using structured questionnaires administered on herd owners. Serological analysis was conducted using competitive enzyme linked immunosorbent assay (c-ELISA) test. Descriptive, univariate, and multivariate statistical analyses were conducted with OpenEpi version 2.3.1 software. Statistical significance was held at P < 0.05. CBPP sero-prevalence in nomadic cattle was 16.2 % (confidence interval (CI) 13.7-19.0) and 9.6 % (CI 6.9-12.9) in sedentary cattle. The overall cattle-level sero-prevalence for two the cattle production systems was 14.0 % (CI 12.1-16.1). Age and agro-ecological zones were significantly (P < 0.001 and P < 0.001, respectively) associated with sero positivity to Mmm in nomadic production. Agro-ecological zone C had the highest sero-prevalence (25.3 %, CI 20.2-31.0). No significant cattle factors were detected in sedentary production. Factors significantly associated with CBPP occurrence at herd-level were contacts with other herds during grazing (P < 0.001) and at watering points (P < 0.001). Others were introduction of new cattle into herd (P < 0.001), outbreaks of CBPP in an area (P < 0.001), socio-cultural factors of cattle gifts and dowry payment (P < 0.001), herd composition of keeping cattle and small ruminants together (P < 0.001), and long trekking during migrations (P = 0.0009). This study had shown the burden of CBPP in the two production systems. Sero-diagnosis and risk factor identification should be institutionalized as elements of epidemio-surveillance and control strategies for CBPP, especially in resource-poor pastoralists' settlements in Nigeria. PMID- 26563272 TI - Effect of feeding Neem (Azadirachta indica) and Acacia (Acacia senegal) tree foliage on nutritional and carcass parameters in short-eared Somali goats. AB - The study was conducted to determine the effects of dried foliage of Acacia senegal and Neem (Azadirachta indica) tree supplementations on feed intake, nutrient digestibility, growth, and carcass parameters in short-eared Somali goats. Twenty male intact short-eared Somali goat yearlings with an average live weight of 16.2 +/- 1.08 (Mean +/- SD) were assigned to four treatment groups, which comprised a basal diet of hay alone (T1) and supplementation with the tree foliages. Supplements consisted Neem tree (T2), A. senegal (T3) and the mixture of the two (1:1 ratio; T4) dried foliages. The crude protein (CP) content of Neem tree foliage, A. senegal, and their mixture were 16.92, 17.5 and 17.01 % of dry matter (DM), respectively. Total DM intake and digestibility of DM and organic matter were significantly (P < 0.001) higher for the supplemented groups. CP digestibility was significantly higher (P < 0.01) for goats supplemented with Neem tree (72 %) and A. senegal (67 %). The final body weights were higher (P < 0.05) for the goats supplemented with A. Senegal. An average daily body weight (BW) gain was higher (P < 0.01) in supplemented groups. The hot carcass weight was higher in the group supplemented with A. senegal (8.3 kg) among the supplemented groups, all of which are higher than the control (4.9 kg). It is concluded that the supplementation with tree foliage, especially with A. senegal tree foliage, on grass hay encouraged a better utilization of nutrients and animal performance as compared to goats fed on a basal diet of grass hay only. PMID- 26563273 TI - Characterization of Escherichia coli isolated from calf diarrhea in and around Kombolcha, South Wollo, Amhara Region, Ethiopia. AB - This study was carried out from October 2012 to end of February 2013 in and around Kombolcha, Amhara regional state, Ethiopia, using a total of 201 neonatal calves aged 1 day to 4 months and suffering from diarrhea. The objectives of the study were to isolate Escherichia coli from diarrheic calves, and to determine E. coli biotypes and risk factors associated with its isolation. The fecal samples were collected, transported, and processed following standard microbiological procedures. Seventy-four isolates of E. coli were identified. Yellowish diarrhea, younger age, and low-colostrum feeding were significantly associated with rate of E. coli isolation (P < 0.05). Then the 74 isolates of E. coli were biotyped using fermentation of 9 sugars and grouped into 12 biotypes; the most dominant was biotype III (36.8 %). Finally, by comparing with studies elsewhere, from the 12 isolated biotypes, 3 of them were suggested to be enteropathogenic E. coli (EPEC), entherotoxigenic E. coli (ETEC), and adhesion and effacing E. coli (AEEC) pathogenic strains. The present study showed that E. coli accounted for 37 % of calf diarrhea, with very diverse biotypes. PMID- 26563274 TI - Detoxified castor meal in substitution of soybean meal in sheep diet: growth performance, carcass characteristics and meat yield. AB - The aim of this study was to evaluate the intake, digestibility, performance, and carcass characteristics of lambs fed different levels of replacement (0, 15, 30, and 45 % based on dry matter, DM) of soybean meal (SM) by detoxified castor meal (DCM). Twenty-four and 32 intact hair lambs of nondescript breed (21.7 +/- 2.6 kg of initial average body weight and approximately 10 months old) were used, respectively, in the intake and digestibility and performance experiments. The diets were composed of buffel grass hay, ground corn grain, and different levels of SM, DCM, and urea, in a roughage-to-concentrate ratio of 40:60. There was no effect of treatments on DM intake. However, crude protein (CP) and neutral detergent fiber (NDF) intakes were higher at 30 and 45 % than at 0 and 15 % of DCM, which in turn showed higher intake of non-fiber carbohydrates (NFC) (P < 0.05). The organic matter, CP, and NDF digestibilities were not affected, but the digestibility of NFC was lower at 30 and 45 % than at 0 % of DCM (P < 0.05). The average daily gain, feed conversion, slaughter and carcass weights, chilling losses, ribeye area, and absolute values and yields of neck, ribs, loin, and leg were not affected. However, the carcass yield was lower at 45 % of DCM and the absolute value of shoulder was lower at 30 and 45 % of DCM (P < 0.05). The replacement of SM by DCM up to 45 % in the feed of lambs did not negatively affect the intake, digestibility, performance, and main carcass features. PMID- 26563275 TI - Novel SNPs in HSPB8 gene and their association with heat tolerance traits in Sahiwal indigenous cattle. AB - Heat shock proteins (HSPs) are expressed in response to heat stress, and the polymorphism in HSP genes at single-nucleotide level has been reported to be associated with heat tolerance and production performance traits in cattle. HSPB8 gene has been mapped on Bos taurus autosome 17 (BTA-17) spanning nearly 13,252 bp and comprising three exons and two introns. The present study was conducted in Sahiwal cows (n = 108) reared in subtropical climate with the objectives to identify SNPs in all three exons and part of intron 1 of HSPB8 gene and to analyze their association with heat tolerance traits in Sahiwal cows. Respiration rate (RR) and rectal temperature (RT) were recorded once during probable extreme hours in different seasons or Temperature-Humidity Index (THI), i.e., winter, spring, and summer. Heat tolerance coefficient (HTC) was also calculated to check the adaptability of the animals during the period of heat stress. The comparative sequence analysis revealed a total two single-nucleotide polymorphisms (SNPs), i.e., g.507G>A in exon 1 and g.881T>C in intron 1 of HSPB8 gene. Out of these two identified SNPs, only one SNP, i.e., g.507G>A, was found to be significantly associated with heat tolerance indicator traits (RR, RT, and HTC) in Sahiwal cows. The perusal of results across different seasons showed the significant (P < 0.01) difference in RR, RT, and HTC between winter, spring, and summer seasons. RR, RT, and HTC were found to be significantly lower (P < 0.01) in GA as compared to GG genotype of g.507G>A SNP of HSPB8 gene. However, in case of another SNP, i.e., g.881T>C, located on intron 1, the RR, RT, and HTC were having non significant association with the different genotypes, i.e., TT and TC. These findings may partly suggest that GA genotype of SNP g.507G>A of HSPB8 gene has a probable role in heat tolerance in Sahiwal cattle and can therefore be utilized as a marker in propagation of thermo-tolerance cattle in hot tropical and subtropical climate. Nevertheless, the involvement of other regulatory mechanisms cannot be overruled. PMID- 26563276 TI - Image Quality of Coronary Computed Tomography Angiography with 320-Row Area Detector Computed Tomography in Children with Congenital Heart Disease. AB - The objective of this study was to assess factors affecting image quality of 320 row computed tomography angiography (CTA) of coronary arteries in children with congenital heart disease (CHD). We retrospectively reviewed 28 children up to 3 years of age with CHD who underwent prospective electrocardiography (ECG)-gated 320-row CTA with iterative reconstruction. We assessed image quality of proximal coronary artery segments using a five-point scale. Age, body weight, average heart rate, and heart rate variability were recorded and compared between two groups: patients with good diagnostic image quality in all four coronary artery segments and patients with at least one coronary artery segment with nondiagnostic image quality. Altogether, 96 of 112 segments (85.7 %) had diagnostic-quality images. Patients with nondiagnostic segments were significantly younger (10.0 +/- 11.6 months) and had lower body weight (5.9 +/- 2.9 kg) (each p < 0.05) than patients with diagnostic image quality of all four segments (20.6 +/- 13.8 months and 8.4 +/- 2.5 kg, respectively; each p < 0.05). Differences in heart rate and heart rate variability between the two imaging groups were not significant. Receiver operating characteristic analyses for predicting patients with nondiagnostic image quality revealed an optimal body weight cutoff of <=5.6 kg and an optimal age cutoff of <=12.5 months. Prospective ECG-gated 320-row CTA with iterative reconstruction provided feasible image quality of coronary arteries in children with CHD. Younger age and lower body weight were factors that led to poorer image quality of coronary arteries. PMID- 26563277 TI - The Significance of Accurate Determination of Gleason Score for Therapeutic Options and Prognosis of Prostate Cancer. AB - The Gleason score (GS) to date remains one of the most reliable prognostic predictors in prostate cancer (PCa). However, the majority of studies supporting its prognostic relevance were performed prior to its modification by the International Society of Urological Pathology (ISUP) in 2005. Furthermore, the combination of Gleason grading and nuclear/nucleolar subgrading (Helpap score) has been shown to essentially improve grading concordance between biopsy and radical prostatectomy (RP) specimens. This prompted us to investigate the modified GS and combigrading (Gleason/Helpap score) in association with clinicopathological features, biochemical recurrence (BCR), and survival. Core needle biopsies and corresponding RP specimens from 580 patients diagnosed with PCa between 2005 and 2010 were evaluated. According to the modified GS, the comparison between biopsy and RP samples resulted in an upgrading from GS 6 to GS 7a and GS 7b in 65% and 19%, respectively. Combigrading further resulted in an upgrading from low grade (GS 6/2a) to intermediate grade PCa (GS 6/2b) in 11.1% and from intermediate grade (GS 6/2b) to high grade PCa (GS 7b/2b) in 22.6%. Overall, well-differentiated PCa (GS 6/2a) was detected in 2.8% of RP specimens, while intermediate grade (GS 6/2b and GS 7a/2b) and high grade cancers (>= GS 7b) accounted for 39.5% and 57.4% of cases, respectively. At a mean follow-up of 3.9 years, BCR was observed in 17.6% of patients with intermediate (9.8%) or high grade PCa (30.2%), while PSA relapse did not occur in GS 6/2a PCa. In conclusion, adding nuclear/nucleolar subgrading to the modified GS allowed for a more accurate distinction between low and intermediate grade PCa, therefore offering a valuable tool for the identification of patients eligible for active surveillance (AS). PMID- 26563278 TI - ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer. AB - Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphism is associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphism could represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy. PMID- 26563279 TI - High Expression of Neuropilin-1 Associates with Unfavorable Clinicopathological Features in Hepatocellular Carcinoma. AB - As a co-receptor for vascular endothelial growth factor (VEGF), Neuropilin-1 (NRP 1) plays an important role in angiogenesis and malignant progression of many human cancers. However, the role of NRP-1 in hepatocellular carcinoma (HCC) is not well understood. The study aimed to detected the expression of Neuropilin-1 in HCC and investigate the association between its expression and the clinicopathological characteristics and prognosis of HCC. Quantitative real-time PCR (qRT-PCR), Western blot, Immunofluorescence and immunohistochemistry (IHC) analyses were performed to characterize the expression of NRP-1 in HCC cell lines and tissues. The association of NRP-1 expression with the clinicopathological characteristics and the prognosis was subsequently assessed. qRT-PCR and Western blot assays revealed that the expression of NRP-1 in HCC was significantly increased relative to that of normal live cells and tissues (P < 0.05,and <0.001, respectively). In addition, high expression of NRP-1 was significantly associated with intrahepatic metastasis (P = 0.036), Edmondson grade (P = 0.007), TNM classification (P = 0.0031), and portal vein invasion (P = 0.004). Furthermore, the HCC patients with high NRP-1 expression had shorter overall survival (OS), and recurrence-free survival (RFS), whereas, patients with low NRP-1 expression had better OS and RFS (P = 0.0035, and 0.0048, respectively). These data indicate that NRP-1 expression may play an important role in the progression of HCC, and that high NRP-1 expression suggests unfavorable clinicopathological characteristics and survival in HCC patients. PMID- 26563280 TI - Pharmacokinetics of sarafloxacin in allogynogenetic silver crucian carp, Carassius auratus gibelio. AB - The pharmacokinetic properties of sarafloxacin were investigated after single intravenous (i.v.) and oral (p.o.) administration of 10 mg/kg body weight (b.w.) in allogynogenetic silver crucian carp at 24-26 degrees C. The plasma concentrations of sarafloxacin were determined by high-performance liquid chromatography. After i.v. administration, the plasma concentration-time data were described by an open two-compartment model. The elimination half-life (T(1/2beta)) was estimated to be 22.58 h. The volume of distribution, V(d(area)), was estimated to be 5.95 L/kg, indicating good tissue penetration of sarafloxacin in the fish. Area under the concentration-time curve (AUC) and total body clearance of sarafloxacin were 56.86 ug.h/mL and 0.18 L/h/kg, respectively. Following p.o. administration, the maximum plasma concentration (C(max)), T(1/2beta), and AUC of sarafloxacin were 0.79 ug/mL, 46.68 h, and 16.58 ug.h/mL, respectively. Absorption of the drug was not good with a bioavailability (F) of 29.15%. Based on a minimum inhibitory concentration (MIC) of 0.00625 to 0.045 MUg/mL for susceptible strains, sarafloxacin p.o. administration at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of fish. PMID- 26563281 TI - Gut melatonin response to microbial infection in carp Catla catla. AB - The purpose of present study was to demonstrate the response of gut melatoninergic system to Aeromonas hydrophila infection for 3 or 6 days and search for its correlation with the activity of different antioxidative and digestive enzymes to focus their interplay under pathophysiological conditions in carp (Catla catla). Microscopic study of gut in infected fish revealed degenerative changes in the tunica mucosa and lamina propria layers with sloughed off epithelial cells in the lumen. The activity of each digestive enzyme was reduced, but the levels of melatonin, arylalkylamine-N-acetyl transferase protein, the key regulator of melatonin biosynthesis, and different enzymatic antioxidants in gut were gradually and significantly increased with the progress of infection. Gut melatonin concentrations in A. hydrophila challenged carp by showing a positive correlation with the activity of each antioxidative enzyme, and a negative correlation with different digestive enzymes argued in favor of their functional relation, at least, during pathological stress. Moreover, parallel changes in the gut and serum melatonin titers indicated possible contribution of gut to circulating melatonin. Collectively, present carp study provided the first data to suggest that endogenous gut melatonin may be implicated to the mechanism of response to microbial infections in any fish species. PMID- 26563282 TI - A richly interactive exploratory data analysis and visualization tool using electronic medical records. AB - BACKGROUND: Electronic medical records (EMRs) contain vast amounts of data that is of great interest to physicians, clinical researchers, and medial policy makers. As the size, complexity, and accessibility of EMRs grow, the ability to extract meaningful information from them has become an increasingly important problem to solve. METHODS: We develop a standardized data analysis process to support cohort study with a focus on a particular disease. We use an interactive divide-and-conquer approach to classify patients into relatively uniform within each group. It is a repetitive process enabling the user to divide the data into homogeneous subsets that can be visually examined, compared, and refined. The final visualization was driven by the transformed data, and user feedback direct to the corresponding operators which completed the repetitive process. The output results are shown in a Sankey diagram-style timeline, which is a particular kind of flow diagram for showing factors' states and transitions over time. RESULTS: This paper presented a visually rich, interactive web-based application, which could enable researchers to study any cohorts over time by using EMR data. The resulting visualizations help uncover hidden information in the data, compare differences between patient groups, determine critical factors that influence a particular disease, and help direct further analyses. We introduced and demonstrated this tool by using EMRs of 14,567 Chronic Kidney Disease (CKD) patients. CONCLUSIONS: We developed a visual mining system to support exploratory data analysis of multi-dimensional categorical EMR data. By using CKD as a model of disease, it was assembled by automated correlational analysis and human curated visual evaluation. The visualization methods such as Sankey diagram can reveal useful knowledge about the particular disease cohort and the trajectories of the disease over time. PMID- 26563283 TI - Role of TRP ion channels in physiology and pathology. PMID- 26563284 TI - Cutaneous immunology: basics and new concepts. AB - As one of the largest organs, the skin forms a mechanical and immunological barrier to the environment. The skin immune system harbors cells of the innate immune system and cells of the adaptive immune system. Signals of the innate immune system typically initiate skin immune responses, while cells and cytokines of the adaptive immune system perpetuate the inflammation. Skin immune responses ensure effective host defense against pathogens but can also cause inflammatory skin diseases. An extensive crosstalk between the different cell types of the immune system, tissue cells, and pathogens is responsible for the complexity of skin immune reactions. Here we summarize the major cellular and molecular components of the innate and adaptive skin immune system. PMID- 26563286 TI - Sit to stand in elderly fallers vs non-fallers: new insights from force platform and electromyography data. AB - BACKGROUND: The sit-to-stand movement requires balance control and coordination between the trunk and lower limbs. For these reasons, it is commonly used in clinics for evaluating lower limb muscle function in the elderly. The aim of the present study was to point out re levant biomechanical and neurophysiological sit to-stand parameters allowing comparison between elderly fallers and non-fallers. METHODS: Ten elderly fallers and thirty non-fallers performed sit-to-stand movements. Sit-to-stand mechanical (maximal and mean force, impulse) and temporal parameters were measured in the vertical and anteroposterior axes using force platforms. Activity of rectus femoris, vastus lateralis, and gastrocnemius lateralis muscles was bilaterally recorded by surface electromyography. RESULTS: Time to realize sit-to-stand movements was significantly longer in elderly fallers compared to non-fallers (p < 0.05). In the same way, maximal vertical force and mean posterior force applied on force platform were significantly lower (p < 0.05) in fallers than in non-fallers individual. At muscular activity level, results showed a main statistical difference in gastrocnemius lateralis muscle activity patterns between faller and non-faller groups. CONCLUSION: Vertical and anteroposterior data from force platform, and gastrocnemius lateralis muscle activity determined during sit-to-stand movement are the most relevant parameters to differentiate fallers and non-fallers. Moreover, these factors highlight different strategies to rise from a chair between faller and non-faller group, suggesting that fallers would constantly adjust their control balance during the sit-to-stand movement. PMID- 26563285 TI - Cutaneous dermatomyositis in the era of biologicals. AB - Dermatomyositis (DM) is a systemic inflammatory condition characterized by cutaneous and muscle findings, in addition to potential involvement of other organ systems. A distinct subtype of DM exists that is categorized by cutaneous findings with absent or minimal muscle involvement, referred to as clinically amyopathic dermatomyositis or dermatomyositis sine myositis. A variety of topical, immunosuppressive, and immunomodulatory therapies have been utilized to treat cutaneous DM. The advent of biological agents including tumor necrosis factor-alpha antagonists, intravenous immunoglobulin, rituximab, and others has allowed for the use of these agents with varying degrees of success for the treatment of cutaneous DM. PMID- 26563287 TI - Osteosarcopenia is more than sarcopenia and osteopenia alone. AB - BACKGROUND: Sarcopenia and osteopenia/osteoporosis show a high prevalence in old age and incur a high risk for falls, fractures, and further functional decline. Physical performance and bone metabolism in patients suffering from the so-called osteosarcopenia-the combination of sarcopenia and osteopenia-are currently still unknown. AIMS: This study investigates physical performance and bone metabolism in osteosarcopenic, prefrail, community-dwelling older adults. METHODS: 68 prefrail adults between 65 and 94 years were assigned to four groups according to mean DXA results: osteosarcopenic [low T-score and low appendicular lean mass (aLM)], sarcopenic (low aLM), osteopenic (low T-score), and controls. Multiple linear regression analysis, adjusted for age, gender, physical activity, and 25 OH-vitamin D3 serum level, was used to identify the influence of being osteosarcopenic, sarcopenic, or osteopenic on physical performance (hand grip, chair rise test, sit-to-stand power, gait speed, SPPB) and serum markers for increased bone turnover [osteocalcin, beta-crosslaps and procollagen type 1 amino terminal propeptide (P1NP)]. RESULTS: Only osteosarcopenic participants showed significantly reduced hand grip strength, increased chair rising time, and STS power time as well as significantly increased bone turnover markers. DISCUSSION: Due to low physical performance and high bone turnover, older adults with osteosarcopenia have to be regarded as the most at-risk population for fractures and further functional decline. CONCLUSIONS: Up-to-date osteoporosis and post fracture management of older persons should aim at both, bone and muscle. PMID- 26563288 TI - US presidential candidates are urged to support open data campaign. PMID- 26563289 TI - Anterior cruciate ligament reconstruction and service in the British Army. AB - BACKGROUND: In 2005, British Army recruiting policy was revised to permit applicants with a history of anterior cruciate ligament reconstruction (ACLR) to be accepted for an initial period of engagement. AIMS: To determine whether personnel with an ACLR history are more likely to be medically discharged due to further injuries and complications than those without. METHODS: A retrospective study of personnel commissioned or enlisted into the British Army between January 2006 and July 2009. ACLR cases were identified from personnel and medical records and were age and sex matched to randomly selected controls. Reasons for discharge were identified. RESULTS: A total of 69 cases and 140 controls were included. A significant increase in risk of medical discharge was found in those with ACLR (incidence risk ratio was 3.04; 95% confidence interval 1.24-7.45). Sixty-one per cent of cases experienced complications linked to their previous surgery. CONCLUSIONS: The current British Army policy on recruitment of those with a history of ACLR should be reviewed in terms of fitness for service and risk of foreseeable harm in these individuals. PMID- 26563296 TI - The influence of perceived behaviour control, attitude and empowerment on reported condom use and intention to use condoms among adolescents in rural Tanzania. AB - BACKGROUND: Despite the declining trends of Human immunodeficiency virus (HIV) infection in Sub-Saharan Africa (SSA), unsafe sexual behaviours among adolescents still represent a public health challenge. It is important to understand factors acting at different levels to influence sexual behaviour among adolescents. This study examined the influence of perceived behaviour control, subjective norms, attitudes and empowerment on intention to use condoms and reported use of condoms among adolescents in rural Tanzania. METHODS: We used a questionnaire to collect data from 403 adolescents aged 14 through 19 years from nine randomly selected secondary schools in the Newala district located in the Southern part of Tanzania. The self-administered questionnaire collected information on sexual practices and factors such as attitudes, subjective norms, perceived behaviour control and empowerment. Binary logistic regression was performed to identify factors associated with intention to use and reported use of condoms. RESULTS: Sexually active adolescents constituted 40.6 % of the sample, among them 49.7 % did not use a condom at last sexual intercourse and 49.8 % had multiple sex partners. Many (85 %) of sexually active respondents had their sexual debut between the ages of 14 to 17 years. Girls became sexually active earlier than boys. Perceived behaviour control predicted intentions to use condoms (AOR = 3.059, 95 % CI 1.324-7.065), thus demonstrating its importance in the decision to use a condom. Empowerment (odds ratio = 3.694, 95 % CI 1.295-10.535) and a positive attitude (AOR = 3.484, 95 % CI 1.132-10.72) predicted reported condom use, thus turning the decision to actions. Subjective norms had only indirect effects on intention and reported use of condoms. CONCLUSION: The findings suggest that unsafe sex practices are prevalent among school adolescents in rural areas of Tanzania. Perceived behaviour control and positive attitudes predict intensions to use condoms whereas empowerment predicts reported condom use. The findings may imply that safe sex promotion interventions that simultaneously address socio-cognitive and ecological determinants of sexual behaviours may improve adolescents' safe sex behaviours. PMID- 26563290 TI - Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling. AB - Glycosylphosphatidylinositols (GPIs) act as membrane anchors of many eukaryotic cell surface proteins. GPIs in various organisms have a common backbone consisting of ethanolamine phosphate (EtNP), three mannoses (Mans), one non-N acetylated glucosamine, and inositol phospholipid, whose structure is EtNP 6Manalpha-2Manalpha-6Manalpha-4GlNalpha-6myoinositol-P-lipid. The lipid part is either phosphatidylinositol of diacyl or 1-alkyl-2-acyl form, or inositol phosphoceramide. GPIs are attached to proteins via an amide bond between the C terminal carboxyl group and an amino group of EtNP. Fatty chains of inositol phospholipids are inserted into the outer leaflet of the plasma membrane. More than 150 different human proteins are GPI anchored, whose functions include enzymes, adhesion molecules, receptors, protease inhibitors, transcytotic transporters, and complement regulators. GPI modification imparts proteins with unique characteristics, such as association with membrane microdomains or rafts, transient homodimerization, release from the membrane by cleavage in the GPI moiety, and apical sorting in polarized cells. GPI anchoring is essential for mammalian embryogenesis, development, neurogenesis, fertilization, and immune system. Mutations in genes involved in remodeling of the GPI lipid moiety cause human diseases characterized by neurological abnormalities. Yeast Saccharomyces cerevisiae has >60 GPI-anchored proteins (GPI-APs). GPI is essential for growth of yeast. In this review, we discuss biosynthesis of GPI-APs in mammalian cells and yeast with emphasis on the lipid moiety. PMID- 26563298 TI - MR cone-beam CT fusion image overlay for fluoroscopically guided percutaneous biopsies in pediatric patients. AB - Lesions only visible on magnetic resonance (MR) imaging cannot easily be targeted for image-guided biopsy using ultrasound or X-rays but instead require MR guidance with MR-compatible needles and long procedure times (acquisition of multiple MR sequences). We developed an alternative method for performing these difficult biopsies in a standard interventional suite, by fusing MR with cone beam CT images. The MR cone-beam CT fusion image is then used as an overlay to guide a biopsy needle to the target area under live fluoroscopic guidance. Advantages of this technique include (i) the ability for it to be performed in a conventional interventional suite, (ii) three-dimensional planning of the needle trajectory using cross-sectional imaging, (iii) real-time fluoroscopic guidance for needle trajectory correction and (iv) targeting within heterogeneous lesions based on MR signal characteristics to maximize the potential biopsy yield. PMID- 26563297 TI - Mapping Purkinje Cell Placement Along the Purkinje Cell Layer: an Analysis of Postmortem Tissue from Essential Tremor Patients vs. Controls. AB - Postmortem studies have reported Purkinje cell loss in essential tremor (ET), and we recently demonstrated a significant increase in the mean distance between Purkinje cell bodies (i.e., a larger gap length distance) in ET cases vs. controls, likely reflecting a disease-associated reduction in Purkinje cells. We now analyze the regularity of distribution of Purkinje cells along the Purkinje cell layer to determine whether there is greater disorganization in ET cases than in age-matched controls. A standard parasagittal, formalin-fixed, tissue block was harvested from the neocerebellum of 50 ET cases and 25 age-matched controls. The gap length distance (MUm) between Purkinje cells was quantified using a nearest neighbor analysis in which the distance between each Purkinje cell body was measured in OpenLAB software, version 5 (Improvision, Waltham, MA) by drawing a freehand line between adjacent Purkinje cell bodies along the entirety of the Purkinje cell layer within a given image. We analyzed the subject-specific variation in the organization of Purkinje cells along the Purkinje cell layer. The 50 ET cases and 25 controls were similar in age at death, gender, and brain weight. Overall, greater variation in gap length distance (i.e., more disorganization) was associated with greater gap length distance (p < 0.001) and younger age (p = 0.020). However, the variation in the Purkinje cell gap length distance (i.e., Purkinje cell organization) did not differ in ET cases and controls (p = 0.330). We observed that the regularity of the distribution of Purkinje cells along the Purkinje cell layer did not differ between ET cases and controls. Several alternative biological interpretations for this finding are discussed. PMID- 26563299 TI - Recombinant human heterodimeric IL-15 complex displays extensive and reproducible N- and O-linked glycosylation. AB - Human interleukin 15 (IL-15) circulates in blood as a stable molecular complex with the soluble IL-15 receptor alpha (sIL-15Ralpha). This heterodimeric IL 15:sIL-15Ralpha complex (hetIL-15) shows therapeutic potential by promoting the growth, mobilization and activation of lymphocytes and is currently evaluated in clinical trials. Favorable pharmacokinetic properties are associated with the heterodimeric formation and the glycosylation of hetIL-15, which, however, remains largely uncharacterized. We report the site-specific N- and O glycosylation of two clinically relevant large-scale preparations of HEK293 derived recombinant human hetIL-15. Intact IL-15 and sIL-15Ralpha and derived glycans and glycopeptides were separately profiled using multiple LC-MS/MS strategies. IL-15 Asn79 and sIL-15Ralpha Asn107 carried the same repertoire of biosynthetically-related N-glycans covering mostly alpha1-6-core-fucosylated and beta-GlcNAc-terminating complex-type structures. The two potential IL-15 N glycosylation sites (Asn71 and Asn112) located at the IL-2 receptor interface were unoccupied. Mass analysis of intact IL-15 confirmed its N-glycosylation and suggested that Asn79-glycosylation partially prevents Asn77-deamidation. IL-15 contained no O-glycans, whereas sIL-15Ralpha was heavily O-glycosylated with partially sialylated core 1 and 2-type mono- to hexasaccharides on Thr2, Thr81, Thr86, Thr156, Ser158, and Ser160. The sialoglycans displayed alpha2-3- and alpha2-6-NeuAc-type sialylation. Non-human, potentially immunogenic glycoepitopes (e.g. N-glycolylneuraminic acid and alpha-galactosylation) were not displayed by hetIL-15. Highly reproducible glycosylation of IL-15 and sIL-15Ralpha of two batches of hetIL-15 demonstrated consistent manufacturing and purification. In conclusion, we document the heterogeneous and reproducible N- and O-glycosylation of large-scale preparations of the therapeutic candidate hetIL-15. Site-specific mapping of these molecular features is important to evaluate the consistent large scale production and clinical efficacy of hetIL-15. PMID- 26563300 TI - The cost of dialysis in low and middle-income countries: a systematic review. AB - BACKGROUND: The cost of dialysis in low and middle-Income countries has not been systematically reviewed. The objective of this article is to systematically review peer-reviewed articles on the cost of dialysis across low and middle income countries. METHODS: PubMed and Embase databases were searched for the year 1998 to March 2013, and additional studies were added from Google Scholar search. An article was included if two reviewers agreed that it had reported cost of dialysis from low and middle-Income countries. RESULTS: The annual cost per patient for hemodialysis (HD) ranged from Int$ 3,424 to Int$ 42,785, and peritoneal dialysis (PD) ranged from Int$ 7,974 to Int$ 47,971. Direct medical cost especially drugs and consumables for HD and dialysis solutions and tubing for PD were the main cost drivers. CONCLUSION: The number of studies on the economics of dialysis in low and middle-income countries is limited. Few papers indicate that dialysis is an expensive form of treatment for the population of these countries and that the poorer countries have an over-proportional burden to finance dialysis services. Further research is needed to determine the cost of dialysis based on a standard methodology grounded on existing economic guidelines and to address the question whether dialysis should be an element of the essential package of health in resource-poor countries. Used data should be as complete as possible. In case of missing data, proxies can be used. In case of developing countries, expert interviews are often used for estimating missing information. PMID- 26563301 TI - Anti-cancer Parasporin Toxins are Associated with Different Environments: Discovery of Two Novel Parasporin 5-like Genes. AB - Cry toxins are primarily a family of insecticidal toxins produced by the bacterium Bacillus thuringiensis (Bt). However, some Cry toxins, called parasporins (PSs), are non-insecticidal and have been shown to differentially kill human cancer cells. Based on amino acid homology, there are currently six different classes of parasporins (PS1-6). It is not known what role parasporins play in nature, nor if certain PSs are associated with Bt found in particular environments. Herein, we present ten parasporin-containing isolates of Bt from the Caribbean island of Trinidad. Genes coding for PS1 and PS6 were found in isolates associated mainly with artificial aquatic environments (e.g., barrels with rain water), while Bt possessing two novel PS5-like genes (ps5-1 and ps5-2), were isolated from manure collected directly from the rectum of cattle. The amino acid sequences inferred from the two PS5-like genes were 51 % homologous to each other, while being only 41 or 45 % similar to PS5Aa1/Cry64Aa, the only reported member of the parasporin five class. The low level of amino acid homology between the two PS5-like genes and PS5Aa1 indicate that the two PS5-like genes may represent a new class of parasporins, or greatly expand the level of diversity within the current parasporin 5 class. PMID- 26563303 TI - In Vitro Activity of Tigecycline Against Acinetobacter baumannii: Global Epidemiology and Resistance Mechanisms. AB - Acinetobacter baumannii is a pathogen of increasing concern, commonly causing outbreaks in the hospital environment. Of particular concern, A. baumannii strains exhibiting resistance to carbapenems, which were previously considered the treatment of choice for infected patients, have dramatically increased worldwide, leaving a few antibacterial choices. Tigecycline, a broad-spectrum modified minocycline derivative, isconsidered as a last resort drug against multidrug-resistant A. baumannii. Though, resistance to tigecycline has emerged and is growing notably following increasing tigecycline usage. Comparative evaluation of the tigecycline resistance rates reported worldwide is challenging due to the absence of official interpretative criteria for in vitro susceptibility testing and the discrepancies among the different susceptibility methodologies used, with broth microdilution being considered the reference method. Tigecycline resistance is mainly associated with resistance-nodulation cell division (RND)-type transporters, mainly the AdeABC, AdeFGH and AdeIJK efflux pumps, but other resistance mechanisms have also been implicated. Tigecycline is still an attractive choice for A. baumannii, but further investigations are warranted so that treatment of MDR Alpha. baumannii could be guided by validated in vitro data. PMID- 26563302 TI - Influence of Culturing Conditions on Bioprospecting and the Antimicrobial Potential of Endophytic Fungi from Schinus terebinthifolius. AB - In this study, we analyzed the antimicrobial activity of extracts harvested from 17 endophytic fungi isolated from the medicinal plant Schinus terebinthifolius. Morphological and molecular analyses indicated that these fungal species belonged to the genera Alternaria, Bjerkandera, Colletotrichum, Diaporthe, Penicillium, and Xylaria. Of the endophytes analyzed, 64.7 % produced antimicrobial compounds under at least one of the fermentation conditions tested. Nine isolates produced compounds that inhibited growth of Staphylococcus aureus, four produced compounds that inhibited Candida albicans, and two that inhibited Pseudomonas aeruginosa. The fermentation conditions of the following endophytes were optimized: Alternaria sp. Sect. Alternata-LGMF626, Xylaria sp.-LGMF673, and Bjerkandera sp. LGMF713. Specifically, the carbon and nitrogen sources, initial pH, temperature, and length of incubation were varied. In general, production of antimicrobial compounds was greatest when galactose was used as a carbon source, and acidification of the growth medium enhanced the production of compounds that inhibited C. albicans. Upon large-scale fermentation, Alternaria sp. Sect. Alternata-LGMF626 produced an extract containing two fractions that were active against methicillin-resistant S. aureus. One of the extracts exhibited high activity (minimum inhibitory concentration of 18.52 ug/mL), and the other exhibited moderate activity (minimum inhibitory concentration of 55.55 ug/mL). The compounds E-2-hexyl-cinnamaldehyde and two compounds of the pyrrolopyrazine alkaloids class were identified in the active fractions by gas chromatography mass spectrometry. PMID- 26563304 TI - In Vitro and In Vivo Biofilm Wound Models and Their Application. AB - Chronic wounds are wounds which are detained in one or more phases of normal wound healing. It is estimated that 1-2 % of the population of developed countries will experience a chronic wound during their lifetime and this number is expected to increase given the growing world population, increase in age, body mass index and associated diseases such as diabetes and cardiovascular diseases. Although several factors contribute to wound healing, presence of bacterial biofilms significantly affects healing and success of wound treatment. This indicates that wound-care therapies should be directed towards targeting biofilms within chronic wounds. Despite this, the role of biofilms in chronic wound pathogenesis and the effect of wound-care therapies against biofilms within wounds are not well understood. In order to address these issues, appropriate biofilm models are necessary. To this end, several model systems mimicking the conditions observed in a biofilm infected chronic wound have been developed. In this review we present an overview of these different in vitro and in vivo biofilm wound model systems and discuss their advantages and disadvantages. PMID- 26563305 TI - Imported and Indigenous cases of Invasive Meningocococcal Disease W:P1.5,2:F1-1: ST-11 in migrants' reception centers. Italy, June-November 2014. AB - We report about three unliked cases of meningococcal meningitis caused by the ST 11/ET-37 strain of Neisseria meningitidis serogroup W. Two of the three cases, detected in Sicily on June and July 2014, were migrants from Mali and Eritrea. The third case was a fatal meningitis occurred on November 2014 in a 37 years old man, working in an immigrant center in Calabria. This report suggests that tetravalent conjugate vaccines (ACYW) should be actively offered to the staff of migrants' reception centers. PMID- 26563306 TI - Advances in Microbiology, Infectious Diseases and Public Health: Fungal Occurrence in the Hair and Skin of Symptomatic Pets in Turin, Italy. AB - Companion animals, often asymptomatic reservoir of fungi, can be important sources of infection in humans, due to the close contact with their owners. The present study was aimed to assess the occurrence of dermatophytes and other fungi isolated from pet dermatological lesions in Turin, Italy. Dermatological specimens were examined for fungal elements by direct microscopy and cultured to detect dermatophytes, other filamentous fungi and yeasts: 247 pets (118 cats, 111 dogs and 18 dwarf rabbits) were positive for fungal detection in culture. Microsporum canis was the most frequent dermatophyte in cats and dogs, whereas Trichophyton mentagrophytes was the most common in rabbits. Among the other fungi, for all examined pets, dematiaceous fungi were the most isolated, followed by Mucorales, penicilli, yeasts and yeast-like fungi, and aspergilli. No gender predisposition was detected for dermatophyte growth; on the contrary, for the other fungi male cats were more susceptible than female. The highest fungal occurrence was recorded in <1-year-old cats for dermatophytes, and in <5-year-old cats and dogs for the other fungi. Autumn was the period associated with a relevant incidence of fungal infection. Finally, fungi were more frequent in non pure-breed cats and in pure-breed dogs. These data underline the importance to timely inform pet owners about the potential health risk of infection caused not only by dermatophytes but also by non-dermatophyte fungi, routinely considered to be contaminants or harmless colonizers, since their role as source of zoonotic infections is not to be excluded. PMID- 26563307 TI - Infectious Agents Associated with Head and Neck Carcinomas. AB - In addition to traditional risk factors such as smoking habits and alcohol consumption, certain microbes also play an important role in the generation of head and neck carcinomas. Infection with high-risk human papillomavirus types is strongly associated with the development of oropharyngeal carcinoma, and Epstein Barr virus appears to be indispensable for the development of non-keratinizing squamous cell carcinoma of the nasopharynx. Other viruses including torque teno virus and hepatitis C virus may act as co-carcinogens, increasing the risk of malignant transformation. A shift in the composition of the oral microbiome was associated with the development of oral squamous cell carcinoma, although the causal or casual role of oral bacteria remains to be clarified. Conversion of ethanol to acetaldehyde, a mutagenic compound, by members of the oral microflora as well as by fungi including Candida albicans and others is a potential mechanism that may increase oral cancer risk. In addition, distinct Candida spp. also produce NBMA (N-nitrosobenzylmethylamine), a potent carcinogen. Inflammatory processes elicited by microbes may also facilitate tumorigenesis in the head and neck region. PMID- 26563308 TI - University of Toronto researcher resigns over "systematic" data fraud. PMID- 26563309 TI - Posterior mitral annuloplasty for enhancing mitral leaflet coaptation: using a strip designed for placement in the posterior annulus. AB - BACKGROUND: In patients with mitral valve regurgitation (MR), posterior mitral annuloplasty (PMA) was performed for mitral valve repair using a strip designed for placement in the posterior annulus, sparing the anterior annulus and anterior half of the commissures. METHODS: Between September 2009 and October 2013, we performed PMA using a novel strip in 74 consecutive patients with MR greater than 3+. Procedures associated with mitral valve repairs were performed in 41 patients (56.9 %), including new chord placement for leaflet prolapse (n=30), patch valvuloplasty for posterior chord rupture (n=4), and posterior leaflet augmentation (n=15). All patients were analyzed by serial echocardiographic follow-up, and preoperative and postoperative computed tomography was performed in 10 randomly selected patients. RESULTS: Hospital death occurred in two patients (2.7 %), and 72 survived patients were completely followed up. At a mean follow-up of 37.2 +/- 15.0 months, the MR grade was zero or 1+ in 64 patients (88.9 %), 2+ in 7 patients (9.7 %), and 3+ in one patient (1.4 %). The mean indexed valve area and mean valve gradient were 1.7 +/- 0.4 cm(2)/m(2) and 3.5 +/ 1.2 mmHg, respectively. The mean leaflet coaptation height in early systole was 12.8 +/- 3.5 mm. During the cardiac cycle, the repaired valves exhibited dynamic changes of 19.5 +/- 9.3 % in the septo-lateral dimensions. No early conversions to valve replacements or late reoperations occurred. None of the patients with remnant or recurrent MR experienced hemolysis. CONCLUSIONS: PMA using a novel strip showed a sufficient coaptation height secondary to reduction of the septo lateral annular dimensions and dynamic changes in the dimensions. It can be expected to be an alternative mitral annuloplasty technique with satisfactory results. PMID- 26563311 TI - Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers. AB - Previous cancer vaccination trials often aimed to activate CD8(+) cytotoxic T cell (CTL) responses with short (8-10mer) peptides and targeted CD4(+) helper T cells (TH) with HLA class II-binding longer peptides (12-16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We monitored 49 patients and found strong CD8(+) T-cell responses in 63% of the patients. In addition, we unexpectedly found CD4(+) TH cell responses against at least two of the five short peptides in 61% (23/38) of the patients analyzed. The two peptides were recognized by HLA-DP4- and HLA-DR-restricted TH1 cells. Some short peptide-reactive (sp)CD4 T cells showed high functional avidity. Here, we show that a short peptide vaccine is able to activate a specific CD4(+) T-cell repertoire in many patients, facilitating a strong combined CD4(+)/CD8(+) T-cell response. PMID- 26563310 TI - Erythropoietin regulates POMC expression via STAT3 and potentiates leptin response. AB - The arcuate nucleus of the hypothalamus is essential for metabolic homeostasis and responds to leptin by producing several neuropeptides including proopiomelanocortin (POMC). We previously reported that high-dose erythropoietin (Epo) treatment in mice while increasing hematocrit reduced body weight, fat mass, and food intake and increased energy expenditure. Moreover, we showed that mice with Epo receptor (EpoR) restricted to erythroid cells (DeltaEpoRE) became obese and exhibited decreased energy expenditure. Epo/EpoR signaling was found to promote hypothalamus POMC expression independently from leptin. Herein we used WT and DeltaEpoRE mice and hypothalamus-derived neural culture system to study the signaling pathways activated by Epo in POMC neurons. We show that Epo stimulation activated STAT3 signaling and upregulated POMC expression in WT neural cultures. DeltaEpoRE mice hypothalamus showed reduced POMC levels and lower STAT3 phosphorylation, with and without leptin treatment, compared to in vivo and ex vivo WT controls. Collectively, these data show that Epo regulates hypothalamus POMC expression via STAT3 activation, and provide a previously unrecognized link between Epo and leptin response. PMID- 26563312 TI - Relationship between melatonin receptor 1B (rs10830963 and rs1387153) with gestational diabetes mellitus: a case-control study and meta-analysis. AB - PURPOSE: Variants rs10830963 (C/G) and rs1387153 (C/T) in MTNR1B have been shown with an increased risk of developing type 2 diabetes and gestational diabetes mellitus. However, the results are still controversial, and evidence was not satisfied. Hence, a case-control study and a further meta-analysis will be performed in this study. METHODS: We recruited 674 GDM patients and 690 controls from Jan 2010 and Jan 2014. The SNPs were genotyped by ABI TaqMan SNP Genotyping Assays. MTNR1B rs10830963 and rs1387153 single nucleotide polymorphisms (SNPs) were performed for association analysis. Then a systematic search of all relevant studies was conducted. A meta-analysis was performed to prove the relationship between melatonin receptor 1B (rs10830963 and rs1387153) with GDM. RESULTS: The case-control study presented that G allele of the rs10830963 and T allele of rs1387153 were significantly associated with increased risk of GDM. The further meta-analysis included other five studies showed that the frequency of MTNR1B rs10830963 G allele and rs1387153 T allele are higher in GDM patients. CONCLUSION: The case-control study proved that the risk allele (G allele) of rs10830963 and (T allele) of rs1387153 lead to a higher risk for GDM. The further meta-analysis provides additional evidence supporting the above results. Due to the limited data currently available in different race population, further studies with large sample sizes are required. PMID- 26563313 TI - Comparison of pregnancy rates in PCOS patients undergoing clomiphene citrate and IUI treatment with different leading follicular sizes. AB - PURPOSE: The objective of the study was to compare the pregnancy rates in PCOS patients undergoing clomiphene citrate (CC) and intrauterine insemination (IUI) treatment with different leading follicular sizes. METHODS: A total of 358 infertile women with PCOS who underwent 563 clomiphene citrate and IUI treatment cycles were included in this prospective study. Treatment cycles were divided into three groups according to leading follicular size on the day of hCG administration: Group I: follicular size 17-18 mm (n = 177), Group II: 19-22 mm (n = 321), and Group III : >22 mm (n = 65). Pregnancy rates were evaluated. Treatment outcomes of the groups were further analyzed related to endometrial thickness measurement on the day of hCG. For this purpose, cycles were placed into three subgroups as follows: endometrial thickness <7, 8-9, and >9 mm. RESULTS: There was no statistically significant difference in clinical pregnancy rate per cycle between the groups (8.5, 10, and 9.2 % for Group I, II, and III, respectively, p = 0.86). In further analyses related to endometrial thickness, no significant difference was also found in pregnancy rate among the groups. CONCLUSION: This results suggest that pregnancy rate is not related to leading follicle size on the day of hCG administration in PCOS patients treated with CC and IUI. In addition, pregnancy rate in women with different follicular sizes is not influenced by the endometrial thickness. PMID- 26563314 TI - Early fetal growth in progesterone-treated IVF pregnancies. AB - PURPOSE: The aim of this study was to compare fetal growth in the first and second trimesters of pregnancy and final birth weights between two groups of women: (a) spontaneous conceptions with reliable menstrual dates and (b) IVF pregnancies on progesterone supplementation during the first trimester. METHODS: We included in the study 73 singleton IVF pregnancies and 138 singleton spontaneous pregnancies. Exclusion criteria were: medications or presence of medical conditions affecting fetal growth. Fetal crown-rump length (CRL) at 10 + 1 to 13 + 6 weeks of gestation, and head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) at 18-24 weeks, were measured prospectively. The birth weights of the babies born were collected and compared. Independent sample t test was applied for comparing quantitative variables with normal distribution, and Wilcoxon-Mann-Whitney test was used for comparison of quantitative variables without normal distribution. RESULTS: IVF fetuses on progesterone supplementation had larger CRL measurements when compared to their counterparts from spontaneous pregnancies (p value = 0.045). Similarly, in the second trimester, the BPD was significantly larger but HC, AC and FL, although larger, did not reach statistical significance. The birthweights of babies between the two groups showed no statistically significant difference, although some IVF babies were born prematurely. CONCLUSIONS: Enhanced fetal growth during the first trimester has been observed with progesterone supplementation in IVF pregnancies. Aspects of enhanced fetal growth were observed in the second trimester but not at birth. The effect of progesterone supplementation on fetal growth needs further investigation. PMID- 26563315 TI - Complete genome sequence of currant latent virus (genus Cheravirus, family Secoviridae). AB - The complete nucleotide sequences of RNA1 and RNA2 of the Holandsky cerveny strain of currant latent virus (CuLV) were determined using next-generation sequencing. The RNA1 is predicted to encode a polyprotein 2124 amino acid long with RdRp motifs. The RNA2 is predicted to encode a polyprotein 957 amino acid long with homology to the capsid protein of apple latent spherical virus and cherry rasp leaf virus. Phylogenetic analysis confirms that CuLV is a new distinct member of the genus Cheravirus. PMID- 26563316 TI - Molecular characterization of coxsackievirus A21 in Shandong, China. AB - Coxsackievirus A21 (CV-A21) is a rarely detected serotype belonging to the species Enterovirus C (EV-C). In this study, we report the isolation and genetic characterization of CV-A21 in Shandong Province, China, during 1997 to 2013. A total of 13 strains were obtained from surveillance of cases of acute flaccid paralysis (AFP) (n = 9) and from environmental sewage (n = 4). Sequence comparison of the VP1 genes revealed high nucleotide sequence similarity (94.1 % to 99.8 % identity) among these Shandong strains during the period of 17 years and 75.8 % to 98.5 % sequence identity to foreign strains. Bayesian phylodynamic evolutionary analysis of Shandong and global CV-A21 VP1 sequences revealed that the inferred CV-A21 ancestral sequence dated back to 1750 (1643-1841) and evolved with 2.943 * 10(-3) substitutions per site per year. Alignment of the deduced VP1 amino acid sequences revealed changes that might alter the hydropathicity of the encoded protein. The complete genome of one strain from 2013 was sequenced and evidence of recombination was detected by similarity plot and bootscanning analyses. This study describes the complete genome characterization and molecular epidemiology of CV-A21 in China and gives further insight into CV-A21 evolution. PMID- 26563317 TI - Pseudorabies in farmed foxes fed pig offal in Shandong province, China. AB - Pseudorabies (PR, Aujeszky's disease) is an acute, highly contagious viral disease resulting in major economic losses to the swine industry. PR is endemic in wild and domestic animals, although its natural host is the pig. Here, we report an outbreak of PR in foxes on a fur-producing farm in Yuncheng county, Shandong, China, that were fed pig offal. The diagnosis of PR was based on nervous signs and standard PCR methods and by isolation of PRV from fox brain tissue in Vero cells. The diagnosis was confirmed by an indirect immunofluorescence assay and electron microscopy. Phylogenetic analysis of a partial (804 nt) viral glycoprotein gC gene sequence indicated that it was likely to be a field strain closely related to a cluster of PRV previously identified in China. PMID- 26563318 TI - Identification of a conserved linear epitope using a monoclonal antibody against non-structural protein 3B of foot-and-mouth disease virus. AB - Foot-and-mouth disease virus (FMDV) is a member of the family Picornaviridae that has caused severe economic losses in many countries of the world. Regular vaccinations have been effectively used to control foot-and-mouth disease (FMD) in countries where the disease is enzootic. Distinguishing between infected and vaccinated animals in herds after immunization is an important component of effective eradication strategies. Nonstructural protein (NSP) 3B of FMDV is part of a larger antigen that is used for this differential diagnosis. In this study, an FMDV serotype-independent monoclonal antibody (MAb) against NSP 3B, 5D12, was generated. Using western blot, it was revealed that MAb 5D12 binds to three fragments of 3B displaying the motifs G(1)PYAGPLERQKPLK(14), K(18)LPQQEGPYAGPMER(32) and V(45)KEGPYEGPVKKPVA(59). The motif G(1)PYAGPLERQKPLK(14) was chosen for further mapping. Different truncated motifs derived from the motif G(1)PYAGPLERQKPLK(14) were expressed as GST-fusion constructs for western blot analysis. The results showed that the 5-aa peptide P(2)YAGP(6) was the minimal epitope reactive to MAb 5D12. Subsequent alanine scanning mutagenesis analysis revealed that Pro(2), Gly(5) and Pro(6) were crucial for MAb 5D12 binding to P(2)YAGP(6). Furthermore, through sequence alignment analysis, the epitope PxxGP recognized by 5D12 was found to be present not only in 3B-1 but also in 3B2 and 3B3 and was highly conserved in seven serotypes of FMDV strains. Western blot analysis also revealed that the peptide epitope could be recognized by sera from FMDV-infected pigs and cattle. Thus, the 5D12-recognized 3B epitope identified here provides theoretical support for the development of MAb 5D12 as a differential diagnosis reagent for FMDV infection. PMID- 26563319 TI - Characterization of the novel T4-like Salmonella enterica bacteriophage STP4-a and its endolysin. AB - While screening for new antimicrobial agents for multidrug-resistant Salmonella enterica, the novel lytic bacteriophage STP4-a was isolated and characterized. Phage morphology revealed that STP4-a belongs to the family Myoviridae. Bacterial challenge assays showed that different serovars of Salmonella enterica were susceptible to STP4-a infection. The genomic characteristics of STP4-a, containing 159,914 bp of dsDNA with an average GC content of 36.86 %, were determined. Furthermore, the endolysin of STP4-a was expressed and characterized. The novel endolysin, LysSTP4, has hydrolytic activity towards outer-membrane permeabilized S. enterica and Escherichia coli. These results provide essential information for the development of novel phage-based biocontrol agents against S. enterica. PMID- 26563320 TI - Cell Density Effects of Frog Skin Bacteria on Their Capacity to Inhibit Growth of the Chytrid Fungus, Batrachochytrium dendrobatidis. AB - Bacterial symbionts on frog skin can reduce the growth of the chytrid fungus Batrachochytrium dendrobatidis (Bd) through production of inhibitory metabolites. Bacteria can be effective at increasing the resistance of amphibians to chytridiomycosis when added to amphibian skin, and isolates can be screened for production of metabolites that inhibit Bd growth in vitro. However, some bacteria use density-dependent mechanism such as quorum sensing to regulate metabolite production. It is therefore important to consider cell density effects when evaluating bacteria as possible candidates for bioaugmentation. The aim of our study was to evaluate how the density of cutaneous bacteria affects their inhibition of Bd growth in vitro. We sampled cutaneous bacteria isolated from three frog species in the tropical rainforests of northern Queensland, Australia, and selected ten isolates that were inhibitory to Bd in standardised pilot trials. We grew each isolate in liquid culture at a range of initial dilutions, sub-sampled each dilution at a series of times during the first 48 h of growth and measured spectrophotometric absorbance values, cell counts and Bd-inhibitory activity of cell-free supernatants at each time point. The challenge assay results clearly demonstrated that the inhibitory effects of most isolates were density dependent, with relatively low variation among isolates in the minimum cell density needed to inhibit Bd growth. We suggest the use of minimum cell densities and fast-growing candidate isolates to maximise bioaugmentation efforts. PMID- 26563321 TI - Effects of Volcanic Pumice Inputs on Microbial Community Composition and Dissolved C/P Ratios in Lake Waters: an Experimental Approach. AB - Volcanic eruptions discharge massive amounts of ash and pumice that decrease light penetration in lakes and lead to concomitant increases in phosphorus (P) concentrations and shifts in soluble C/P ratios. The consequences of these sudden changes for bacteria community composition, metabolism, and enzymatic activity remain unclear, especially for the dynamic period immediately after pumice deposition. Thus, the main aim of our study was to determine how ambient bacterial communities respond to pumice inputs in lakes that differ in dissolved organic carbon (DOC) and P concentrations and to what extent these responses are moderated by substrate C/P stoichiometry. We performed an outdoor experiment with natural lake water from two lakes that differed in dissolved organic carbon (DOC) concentration. We measured nutrient concentrations, alkaline phosphatase activity (APA), and DOC consumption rates and assessed different components of bacterial community structure using next-generation sequencing of the 16S rRNA gene. Pumice inputs caused a decrease in the C/P ratio of dissolved resources, a decrease in APA, and an increase in DOC consumption, indicating reduced P limitation. These changes in bacteria metabolism were coupled with modifications in the assemblage composition and an increase in diversity, with increases in bacterial taxa associated with biofilm and sediments, in predatory bacteria, and in bacteria with gliding motility. Our results confirm that volcanic eruptions have the potential to alter nutrient partitioning and light penetration in receiving waterways which can have dramatic impacts on microbial community dynamics. PMID- 26563322 TI - A perspective on sympathetic renal denervation in chronic congestive heart failure. AB - Medical therapy has indisputably been the mainstay of management for chronic congestive heart failure. However, a significant percentage of patients continue to experience worsening heart failure (HF) symptoms despite treatment with multiple therapeutic agents. Recently, catheter-based interventional strategies that interrupt the renal sympathetic nervous system have shown promising results in providing better symptom control in patients with HF. In this article, we will review the pathophysiology of HF for better understanding of the interplay between the cardiovascular system and the kidney. Subsequently, we will briefly discuss pivotal renal denervation (RDN) therapy trials in patients with resistant hypertension and then present the available evidence on the role of RDN in HF therapy. PMID- 26563325 TI - Errors in cause-of-death statement on death certificates in intensive care unit of Kathmandu, Nepal. AB - BACKGROUND: Death certificates (DC) are one of the most important medico-legal documents that physicians work through. DCs are extensively used in health statistics for epidemiological studies, and in health policy planning as a public health resource tool. Cause-of-death (COD) statement, which is vulnerable to various errors, is the vital part of a DC that has the potential to mislead the policy makers and statisticians. Hence, we evaluated and analyzed the errors prevalent in COD statement of DC. METHODS: A retrospective observational study was conducted at medical Intensive Care Unit (ICU) of Blue Cross Hospital, Kathmandu, Nepal within two years of study period. A total of 204 medical records of the deceased patients were reviewed. Three sub-headings of COD statement of DC Part I Immediate COD (ICOD), Part I Underlying COD (UCOD), and Part II Other significant conditions (OSC) were extensively evaluated for the major medical errors. RESULTS: The study found errors in 78.4 % of DCs. The highest number of errors was in UCOD (83 %). Most common errors were "Mechanism of Death- terminal event" in ICOD, "More than one competing causes" in UCOD, and "OSC present but not listed" in OSC. The error in DC was found to be statistically significant with the severity of sepsis (p = 0.003), and presence of chronic organ failures (p = 0.034). Age, time of death, source of admission, and duration of ICU stay were not found to be statistically associated with the errors in DC. CONCLUSION: Prevalence of errors in DC was quite high. Most errors were committed in underlying cause of death, which is the most important part of DC. Complexity of the cases was the key factor that increased the risks of committing errors. Specific education should supersede general educational interventions to minimize the errors considerably in writing DC in complex cases. PMID- 26563324 TI - Characteristics Relating to Adherence and Persistence to Basal Insulin Regimens Among Elderly Insulin-Naive Patients with Type 2 Diabetes: Pre-Filled Pens versus Vials/Syringes. AB - INTRODUCTION: Previous studies have found higher rates of adherence in patients with type 2 diabetes mellitus (T2DM) using insulin pens compared to vial and syringe administration; however, little evidence is available to support this observation in elderly patients. METHODS: This was a retrospective claims database analysis of a predominantly elderly Medicare Advantage with Prescription Drug (MAPD) insurance population consisting of 3172 insulin-naive patients with T2DM who initiated basal insulin using pre-filled pens or vial and syringe ('vial'). The index date was defined by the first pharmacy claim for basal insulin. Adherence, measured as proportion of days covered (PDC) and medication possession ratio (MPR), and persistence were evaluated in a 12-month follow-up period using an adjusted days' supply. Multivariate regression analyses and a Cox proportional hazards model were used to identify characteristics associated with adherence and non-persistence, respectively, and compare findings between the pen and vial groups. RESULTS: The pen cohort was slightly younger than the vial cohort (69.4 vs. 70.1 years, respectively; P = 0.0338). Similar proportions of male patients (53.3% vs. 56.8%; P = 0.0529) occurred in both cohorts, and lower Deyo-Charlson Comorbidity Index (4.4 vs. 5.0; P < 0.0001) was found for the pen cohort. Adjusted mean PDC was significantly higher in the pen cohort than the vial cohort (0.67 vs. 0.50; P < 0.001), as was mean MPR (0.75 vs. 0.57; P < 0.0001). Adjusted odds for adherence (PDC >= 80%) showed a positive association with use of an insulin pen (odds ratio = 2.19, 95% CI: 1.86-2.59). The adjusted risk of non-persistence (discontinuation) was significantly lower (58%) in the pen cohort relative to the vial cohort (hazard ratio = 0.42, 95% CI: 0.38-0.45). Key limitations include assumptions related to accuracy and comprehensiveness of claims data, and specifically days' supply data used to measure insulin adherence. CONCLUSION: These findings suggest that pen devices improved insulin therapy adherence in a primarily elderly MAPD population with T2DM. FUNDING: Novo Nordisk Pharmaceuticals, Inc. PMID- 26563326 TI - [Robert Fischer: 07.02.1930 - 18.08.2015]. PMID- 26563323 TI - Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 h in Healthy Japanese Subjects. AB - INTRODUCTION: Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2alpha receptor agonist in clinical development for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. We evaluated the effect of latanoprostene bunod 0.024% instilled once daily (QD) on lowering IOP over a 24-h period in healthy Japanese subjects following 14 days of treatment. METHODS: This was a single-arm, single-center, open-label clinical study of 24 healthy Japanese male volunteers. A baseline IOP profile was established in both eyes in the sitting position at 8 PM, 10 PM, 12 AM, 2 AM, 4 AM, 8 AM, 10 AM, 12 PM, and 4 PM using a Goldmann applanation tonometer. Subjects subsequently instilled latanoprostene bunod 0.024% QD at 8 PM for 14 days in both eyes. The absolute and change from baseline in sitting IOP was assessed on day 14. RESULTS: The mean (SD) age of the subjects was 26.8 (6.3) years, and mean (SD) baseline IOP was 13.6 (1.3) mmHg in the study eye. Latanoprostene bunod 0.024% instilled QD for 14 days reduced IOP at all the evaluated time points (P < 0.001) with a mean (SD) 24-h reduction of 3.6 (0.8) mmHg or 27% from the baseline in the study eye. Peak and trough IOP lowering occurred at 8 AM and 8 PM (12 and 24 h following instillation) with a mean reduction of 4.2 (1.8) mmHg, or 30%, and 2.8 (2.2) mmHg, or 20%, respectively. Punctate keratitis and ocular hyperemia, both mild in severity, were the most common adverse events. CONCLUSION: Latanoprostene bunod ophthalmic solution 0.024%, dosed QD for 14 days, significantly lowered mean IOP in healthy Japanese subjects during the entire 24-h period. Studies of latanoprostene bunod in patients diagnosed with normal tension glaucoma are warranted. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01895985. FUNDING: Bausch & Lomb, Inc. PMID- 26563327 TI - In Utero Diagnosis of Niemann-Pick Type C in the Absence of Family History. AB - Niemann-Pick type C (NPC) disease is a recessive disorder that results in unesterified cholesterol accumulating in the lysosomal and late endosomal system. It is caused by mutations in NPC1 or NPC2 genes and leads to systemic and neurodegenerative symptoms. Few cases of prenatal presentation of NPC have been reported and only two cases in the absence of previous family history, indicating the diagnosis is particularly difficult in such a situation. We report a prenatal diagnosis of NPC in a couple without family history. An ultrasound screening at 22 weeks of gestation (WG) detected fetal ascites and hepatomegaly, which were still present at 25, 27, and 29 WG, and a splenomegaly progressively appeared. No placentomegaly or other signs of hydrops fetalis were observed. The diagnostic of NPC was prenatally confirmed by a filipin test and NPC1 sequencing and multiplex ligation-dependent probe amplification assay which revealed a maternal missense mutation (c.2608T>C; p.Ser870Pro) and a paternal deletion of exons 5 to 25. This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis. PMID- 26563328 TI - In Patients with an alpha-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease. AB - BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an alpha-galactosidase A enzyme deficiency due to pathogenic variants in the alpha-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling. OBJECTIVES: We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis. METHODS: All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of >=1 abnormal QST modality and an abnormal IENFD. RESULTS: Twenty-six patients participated (nonclassical FD n = 18, 9 males; no FD n = 5, 3 males; uncertain n = 3, 1 male). Of the patients classified as nonclassical FD, 28% had >=1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had >=1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%. CONCLUSIONS: In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD. PMID- 26563329 TI - Sixty seconds on . . . HRT. PMID- 26563330 TI - Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation. AB - PURPOSE: We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury. METHODS AND MATERIALS: ADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation. Dose responses were tested at doses of 0-90 Gy in C57BL/6 and C3H/HeJCr mice at 6 weeks after irradiation. The volume effect was evaluated with 1-, 3-, and 5-mm diameter collimators at 1-4 weeks after 90-Gy irradiation. RESULTS: ADFIR caused gross local lung injury of the inflated lung in just 1 week, with extensive hyaline material visible in the irradiated area. The fibrosing process was initiated as early as 2 weeks after irradiation. C3H and C57 mice did not show significant differences in dose response. Six weeks after irradiation, the radiation dose response curve had a sigmoidal shape, where the lag, log, and stationary phases occurred at <40, 50-70, and >80 Gy, respectively. ADFIR induced substantial volume-dependent structural and functional damage to the lungs, and the volume changes of lung consolidation on micro-CT correlated inversely with lung fibrosis over time. CONCLUSIONS: We determined the time, dose, and volume responses in our established small animal model, and found that lung injury was substantially accelerated and phenotypically different from that of prior studies using non ablative hemi-thorax and complete thorax irradiation schemes. PMID- 26563331 TI - Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation Induced Lung Injury in Mice. AB - PURPOSE: The present study was designed to investigate the effects of WP1066, a specific inhibitor of STAT3 signaling, on radiation-induced lung injury in mice. METHODS: C57BL/6J mice were subjected to a single thoracic irradiation of 15 Gy X ray and WP1066 was administrated through intraperitoneal injection. The early and delayed treatment groups were treated with WP1066 during the first 2 weeks and the second 2 weeks, respectively. The therapeutic effects of WP1066 were evaluated by survival analysis, histological examination, and measurement of inflammatory parameters and collagen deposition. The activation of STAT3 pathway was also estimated by immunohistochemical staining and Western blotting. RESULTS: Delayed treatment of WP1066, but not early treatment, prolonged survival time and prevented the development of radiation pneumonitis and the subsequent lung fibrosis in mice. WP1066 treatment also significantly suppressed the activation of STAT3 signaling in the irradiated lung tissues. CONCLUSIONS: The activation of STAT3 pathway might play an important part in the pathogenesis of radiation induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. PMID- 26563332 TI - Diagnostic Utility of Angiotensin-Converting Enzyme in Sarcoidosis: A Population Based Study. AB - PURPOSE: Sarcoidosis is a disease with heterogenous clinical presentations. Diagnosis of sarcoidosis is often challenging with the lack of gold standard tests. In this study, we investigated the diagnostic utility of angiotensin converting enzyme (ACE) for diagnosis of sarcoidosis. METHODS: A cohort of Olmsted County, Minnesota residents who were diagnosed with sarcoidosis between January 1, 1984 and December 31, 2013 was identified based on individual medical record review. ACE levels recorded in the medical records of all subjects at the time of diagnosis were extracted. Comparator subjects were residents of Olmsted County, Minnesota who had ACE levels tested the same time period but did not have a diagnosis of sarcoidosis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the c-statistic of high versus low/normal ACE to diagnose sarcoidosis were calculated. RESULTS: A total of 3277 Olmsted County residents age >=18 years had at least one ACE test in 1984-2013. The sarcoidosis incidence cohort contained 295 Olmsted County residents diagnosed with sarcoidosis in 1984-2013. Of these, ACE tests were obtained in 251. The sensitivity and specificity of high ACE for diagnosis of sarcoidosis were 41.4 % (95 % CI 35.3-47.8 %) and 89.9 % (95 % CI 88.8-91.0 %), respectively. The PPV and NPV in this population were 25.4 % (95 % CI 21.3-29.9 %) and 94.9 % (95 % CI 85.0 87.4 %). CONCLUSIONS: This study demonstrated a poor sensitivity and insufficient specificity of high ACE for diagnosis of sarcoidosis suggesting a limited role of ACE in clinical practice. PMID- 26563333 TI - Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause. AB - Recently, the placenta mesotherapy has been widely used to treat menopause. Placenta contains amino acids, peptides, minerals, and estrogen. Here, we investigated the estrogen-like osteoprotective effects of glycine (a main ingredient of placenta) in in vitro and in vivo models of menopause. We assessed the effect of glycine on MG-63 osteoblast cell line, MCF-7 estrogen-dependent cell line, and ovariectomized (OVX) mice. Glycine significantly increased the MG 63 cell proliferation in a dose-dependent manner. Activity of alkaline phosphatase (ALP) and phosphorylation of extracellular-signal-regulated kinase were increased by glycine in MG-63 cells. Glycine also increased the BrdU incorporation and Ki-67 mRNA expression in MCF-7 cells. Glycine induced the up regulation of estrogen receptor-beta mRNA expression and estrogen-response element-luciferase activity in MG-63 and MCF-7 cells. In OVX mice, glycine was administered orally at a daily dose of 10 mg/kg per day for 8 weeks. Glycine resulted in the greatest decrease in weight gain caused by ovariectomy. Meanwhile, vaginal weight reduced by ovariectomy was increased by glycine. Glycine significantly increased the ALP activity in OVX mice. MicroCT-analysis showed that glycine significantly enhanced bone mineral density, trabecular number, and connectivity density in OVX mice. Moreover, glycine significantly increased the serum 17beta-estradiol levels reduced by ovariectomy. Glycine has an estrogen-like osteoprotective effect in menopause models. Therefore, we suggest that glycine may be useful for the treatment of menopause. PMID- 26563334 TI - miR-27a and miR-214 exert opposite regulatory roles in Th17 differentiation via mediating different signaling pathways in peripheral blood CD4+ T lymphocytes of patients with relapsing-remitting multiple sclerosis. AB - Multiple sclerosis (MS) is one of the most prevalent autoimmune diseases, which involves the central nervous system. In this illness, Treg/Th17 cell imbalance causes the defect. Several studies revealed that T helper 17 (Th17) cells play a crucial role in pathogenesis, inflammation, and autoimmunity of several autoimmune diseases such as MS. In the present study, we assessed transcript levels of miR-27a and miR-214, in purified CD4+ T cells of MS patients, during relapsing and remitting phases in inducing differentiation of T naive cells to Th17 cells. Forty RR-MS patient samples including those in relapsing (n=20) and remitting (n=20) phases were participated in this study. In addition, transcript levels of IL-17A, RORgammat, IL-23R, Foxp3, and TGF-beta in purified CD4+ T cells of patients in relapsing and remitting phases of RRMS patients were compared to healthy controls. Expression levels of miR-27a and miR-214 were measured by RT qPCR and compared to healthy control group (n=10). Data indicated upregulation of miR27a in relapsing phase of multiple sclerosis compared to remitting phase and healthy volunteers while miR-214 downregulated in relapsing phase of MS compared to remitting phase and healthy volunteers. In silico studies demonstrated pathways which miR-27a and miR-214 could effect on CD4+ T cell lineage fate including TGF-beta and mTOR signaling, respectively. Our data suggest that miR 27a may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation while miR-214 has an adverse effect. PMID- 26563335 TI - [Diagnosis and treatment of sarcoidosis. Current standards]. AB - Sarcoidosis is a granulomatous disease that mainly affects the lungs and intrathoracic lymph nodes; however, virtually any organ can be affected. As an orphan disease, recommendations are mainly based on observational or small randomized studies as well as experts' opinion. Diagnosing sarcoidosis requires proof of non-necrotizing granulomas in patients with a compatible symptomatic pattern and the exclusion of other granulomatous diseases. Granulomas can be detected best in the lungs or intrathoracic lymph nodes. Therefore, bronchoscopy and endobronchial ultrasound with biopsies of lymph nodes are the major tools to diagnose sarcoidosis. Frequently, close follow-up and symptomatic therapy are sufficient to allow for spontaneous resolution. In case of functional organ impairment, cardial or CNS involvement, or other complications, steroid therapy is necessary with a starting dose of 0.5 mg/kg body weight that should be tapered off over 6-12 months. Steroid-refractory disease can be treated by adding methotrexate or azathioprine, two drugs long known in sarcoidosis treatment. Monoclonal antibodies against TNF and lung transplantation are further therapeutic options. PMID- 26563336 TI - Yield of left ventricular dyssynchrony by gated SPECT MPI in patients with heart failure prior to implantable cardioverter-defibrillator or cardiac resynchronization therapy with a defibrillator: Characteristics and prediction of cardiac outcome. AB - BACKGROUND: Mechanical left ventricular dyssynchrony (MLVD) might contribute in the therapeutic decision-making in patients with heart failure (HF) prior to cardiac resynchronization therapy (CRT). Our aim was to assess MLVD in patients with HF prior to implantable cardioverter-defibrillator (ICD) compared to patients with CRT-D. METHODS: In a prospective study, patients with LVEF <= 35% who were scheduled for ICD or CRT-D, underwent gated SPECT myocardial perfusion imaging with technetium 99m sestamibi within 3 months prior procedure. MLVD was measured by phase analysis. RESULTS: The study cohort consisted of 143 patients, 71 with ICD and 72 with CRT-D. Age 68.3 +/- 11 and LVEF 24 +/- 6%. Phase standard deviation (SD) was 62.5 +/- 18 and 59.7 +/- 20 (P = NS), respectively. During follow-up of 23.7 +/- 12.1 months, there were 10 vs 14 cardiac death in ICD and CRT-D, respectively (P = NS), hospitalization for HF, in 34 vs 53 (P < .001). In multivariate analysis, Phase SD was the independent predictor for cardiac death [HR 2.66 (95% CI 1.046-6.768), P = .04]. Kaplan-Meier curves of phase SD of 60 degrees significantly identified ICD patients with and without cardiac deaths and hospitalization for HF exacerbation. CONCLUSIONS: MLVD by phase SD can identify patients with cardiac events and predict cardiac death in patients treated with ICD. PMID- 26563337 TI - Print media coverage of primary healthcare and related research evidence in South Africa. AB - BACKGROUND: The news media is located at the nexus of the public and policy agendas and provides a window into issues concerning the public. Therefore, it could be a powerful tool for advocating for citizens' health and could help promote evidence-based primary health systems responsive to the needs of citizens. However, research on the coverage of primary healthcare and related research evidence in the South African print media is virtually non-existent. METHODS: We examined 2,077 news stories that covered primary healthcare from 25 South African newspapers retrieved from the Lexis-Nexis online archive over a 16 year period (1997-2012). We analysed basic characteristics and conducted a content analysis of the news stories. RESULTS: Of the 2,077 news stories that mentioned primary healthcare, this was the main focus in 8.3% (n = 173). Of these, 45.7% discussed issues relating to clinics, whereas issues relating to community health workers and nurses were covered by 42.8% and 34.1% of news stories, respectively. The number of news stories discussing infectious diseases (55.5%) was more than twice the number discussing non-communicable diseases (21.4%). HIV/AIDS/TB illness- and service-related issues were covered by 54.3% of news stories and social determinants of health by 22%. Issues relating to how healthcare is organised to deliver services to the people received substantial coverage in the print media, with 72.8% discussing delivery arrangements, 72.3% governance arrangements, and 55% financial arrangements. A small fraction of news stories (7.5%) discussed research studies but none discussed a systematic review. CONCLUSION: Our study underscores the potential role of media analyses in illuminating patterns in print media coverage of health issues. It also shows that an understanding of coverage of health research evidence could help spur efforts to support the climate for evidence-informed health policymaking. Researchers in low- and middle-income countries need to be more proactive in making use of media analyses to help illuminate health related issues that require the attention of health policymakers, stakeholders and reporters, and to identify potential areas of research. PMID- 26563338 TI - Multidisciplinary team care for people with rheumatoid arthritis: a systematic review and meta-analysis. AB - The objective of this study was to systematically review the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of multidisciplinary team (MDT) care for the management of disability, disease activity and quality of life (QoL) in adults with rheumatoid arthritis (RA). Data sources identified published (MEDLINE, PsychINFO, EMBASE, CINAHL, Web of Science, CENTRAL) and unpublished (OpenGrey) literature. Independent data extraction and quality assessment, using the Cochrane risk of bias tool, were conducted by two reviewers. The primary outcome was change in disability at 12 months; secondary outcomes included disability at other time points and disease activity and QoL at 12 months. Where possible, the pooled effect sizes were calculated for inpatient or outpatient MDT interventions. Four hundred and fifteen studies were retrieved. Twelve manuscripts, which reported 10 RCTs, representing 1147 participants were included. Only data from five high- or moderate-quality trials were pooled according to clinical setting. There was no difference in disability between inpatient MDT care and any comparison group [mean difference (95% confidence intervals) 0.04, -0.13 to 0.20] or between outpatient MDT care and comparison groups (0.09, -0.07 to 0.25) at 12 months. There was no difference in disability at 2 years or <12 months or disease activity and QoL at 12 months between MDT care and any comparison group. There is limited evidence evaluating the effect of MDT care on disability, disease activity or QoL in people with RA. There is likely to be no effect of MDT care on disability at 12 months or other time points. PMID- 26563339 TI - Gangrene in Takayasu's arteritis: a report of two cases and review of literature. AB - Takayasu's arteritis (TA) is a granulomatous large vessel vasculitis more commonly seen in India. The vascular inflammation in TA results in stenoses of affected vessels. Usually this is a slow process with good collateral circulation; only rarely does critical limb ischemia result. We present two patients of TA who presented with gangrene of extremities, and review eight prior such patients reported in the literature. With appropriate diagnosis and treatment with oral corticosteroids and low-dose aspirin, none of our patients had recurrence at a mean follow-up of 3.8 +/- 2.8 years. Although rare, TA can present with gangrene and rheumatologists need to be aware of this unusual but limb-threatening manifestation of TA to institute appropriate therapy in a timely manner. PMID- 26563340 TI - A large lingual thyroid extending to the epiglottis. AB - A 22-year-old man presented to our department with a mass on the base of his tongue. He had a cavernous voice causing a moderate speech disorder, and he had some difficulty in swallowing. He had severe problems with sleep, associated with apnoea. In a fibreoptic laryngoscopic examination, a large 4*5 cm vascular mass was detected extending from the base of the patient's tongue to his epiglottis. It covered the epiglottis. Thyroid scintigraphy showed only thyroid tissue on the base of the tongue. Surgery was initiated transorally under the guidance of a rigid endoscope, but as the mass continued extended to the epiglottis, a transhyoid approach was taken. At a 3-month follow-up, the patient was symptom free. Electrocautery-assisted resection under the guidance of a rigid endoscope can reliably be used in surgery of a lingual thyroid. However, a transhyoid approach provides a better view and also helps in achieving haemostasis. PMID- 26563341 TI - Novel transient alien limb phenomenon heralding a diabetic hyperosmolar non ketotic state with leukoaraiosis: a video presentation. PMID- 26563342 TI - Histological determination of the human origin from dry bone: a cautionary note for subadults. AB - Anthropologists are frequently required to confirm or exclude the human origin of skeletal remains; DNA and protein radioimmunoassays are useful in confirming the human origin of bone fragments but are not always successful. Histology may be the solution, but the young subadult structure could create misinterpretation. Histological tests were conducted on femur and skull of 31 human subjects. Each sample was observed focusing on presence or absence of fibrous bone, lamellar bone, radial lamellar bone, plexiform bone, reticular pattern, osteon banding, Haversian bone, primary osteons, secondary osteon and osteon fragments. Samples were divided into five age classes; 1 (<1 year), 2 (1-5 years), 3 (6-10 years), 4 (11-15 years) and 5 (16-20 years). Regarding femurs, class 1 presented the following: 87.5% fibrous bone, 37.5% plexiform bone, 12.5% reticular pattern and 12.5% lamellar bone radially oriented. Class 2 showed 37.5% of fibrous bone, 12.5% of reticular pattern and 37.5% of osteon banding. In the higher age classes, the classical human structures, lamellar bone and osteons were frequently visible, except for one case of reticular pattern, generally considered a distinctive non-human structure. The situation appeared different for the skull, where there was a lack of similar information, both in human and non-human. An analysis of the percentage of lamellar bone and osteons was conducted on femur and skull fragments. A trend of increase of primary osteon number and a decrease of the lamellar bone area has been detected in the femur. The present study has therefore shed some light on further pitfalls in species determination of subadult bone. PMID- 26563344 TI - Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes. AB - Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235 treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo. PMID- 26563345 TI - A strong root-specific expression system for stable transgene expression in bread wheat. AB - KEY MESSAGE: A strong, stable and root-specific expression system was developed from a rice root-specific GLYCINE - RICH PROTEIN 7 promoter for use as an enabling technology for genetic manipulation of wheat root traits. Root systems play an important role in wheat productivity. Genetic manipulation of wheat root traits often requires a root-specific or root-predominant expression system as an essential enabling technology. In this study, we investigated promoters from rice root-specific or root-predominant expressed genes for development of a root expression system in bread wheat. Transient expression analysis using a GREEN FLUORESCENT PROTEIN (GFP) reporter gene driven by rice promoters identified six promoters that were strongly expressed in wheat roots. Extensive organ specificity analysis of three rice promoters in transgenic wheat revealed that the promoter of rice GLYCINE-RICH PROTEIN 7 (OsGRP7) gene conferred a root specific expression pattern in wheat. Strong GFP fluorescence in the seminal and branch roots of wheat expressing GFP reporter driven by the OsGRP7 promoter was detected in epidermal, cortical and endodermal cells in mature parts of the root. The GFP reporter driven by the promoter of rice METALLOTHIONEIN-LIKE PROTEIN 1 (OsMTL1) gene was mainly expressed in the roots with essentially no expression in the leaf, stem or seed. However, it was also expressed in floral organs including glume, lemma, palea and awn. In contrast, strong expression of rice RCg2 promoter driven GFP was found in many tissues. The GFP expression driven by these three rice promoters was stable in transgenic wheat plants through three generations (T1-T3) examined. These data suggest that the OsGRP7 promoter can provide a strong, stable and root-specific expression system for use as an enabling technology for genetic manipulation of wheat root traits. PMID- 26563348 TI - British nurse makes "full recovery" from reactivated Ebola virus. PMID- 26563346 TI - Suppression of the D-class MADS-box AGL11 gene triggers seedlessness in fleshy fruits. AB - KEY MESSAGE: Seedlessness, one of the most desired traits in fleshy fruits, can be obtained altering solely AGL11 gene, a D -class MADS-box. Opposite to overlapping functions described for ovule identity. AGAMOUS like-11 (AGL11) is a D-class MADS-box gene that determines ovule identity in model species. In grapevine, VviAGL11 has been proposed as the main candidate gene responsible for seedlessness because ovules develop into seeds after fertilization. Here, we demonstrate that AGL11 has a direct role in the determination of the seedless phenotype. In grapevine, broad expression analysis revealed very low expression levels of the seedless allele compared to the seeded allele at the pea-size berry stage. Heterozygous genotypes have lower transcript accumulation than expected considering the diploid nature of grapevine, thereby revealing that the dominant phenotype previously described for seedlessness is based on its expression level. In a seeded somatic variant of Sultanina (Thompson Seedless) that has well developed seeds, Sultanine Monococco, structural differences were identified in the regulatory region of VviAGL11. These differences affect transcript accumulation levels and explain the phenotypic differences between the two varieties. Functional experiments in tomato demonstrated that SlyAGL11 gene silencing produces seedless fruits and that the degree of seed development is proportional to transcript accumulation levels. Furthermore, the genes involved in seed coat development, SlyVPE1 and SlyVPE2 in tomato and VviVPE in grapevine, that are putatively controlled by SlyAGL11 and VviAGL11, respectively, are expressed at lower levels in silenced tomato lines and in seedless grapevine genotypes. In conclusion, this work provides evidence that the D-class MADS-box AGL11 plays a major and direct role in seed development in fleshy fruits, providing a valuable tool for further analysis of fruit development. PMID- 26563347 TI - Biotechnological advances in tea (Camellia sinensis [L.] O. Kuntze): a review. AB - KEY MESSAGE: This article presents a comprehensive review on the success and limitations of biotechnological approaches aimed at genetic improvement of tea with a purpose to explore possibilities to address challenging areas. Tea is a woody perennial tree with a life span of more than 100 years. Conventional breeding of tea is slow and limited primarily to selection which leads to narrowing down of its genetic base. Harnessing the benefits of wild relatives has been negligible due to low cross-compatibility, genetic drag and undesirable alleles for low yield. Additionally, being a recalcitrant species, in vitro propagation of tea is constrained too. Nevertheless, maneuvering with tissue/cell culture techniques, a considerable success has been achieved in the area of micropropagation, somatic embryogenesis as well as genetic transformation. Besides, use of molecular markers, "expressomics" (transcriptomics, proteomics, metabolomics), map-based cloning towards construction of physical maps, generation of expressed sequenced tags (ESTs) have facilitated the identification of QTLs and discovery of genes associated with abiotic or biotic stress tolerance and agronomic traits. Furthermore, the complete genome (or at least gene space) sequence of tea is expected to be accessible in the near future which will strengthen combinational approaches for improvement of tea. This review presents a comprehensive account of the success and limitations of the biotechnological tools and techniques hitherto applied to tea and its wild relatives. Expectedly, this will form a basis for making further advances aimed at genetic improvement of tea in particular and of economically important woody perennials in general. PMID- 26563349 TI - Navigated MRI-guided liver biopsies in a closed-bore scanner: experience in 52 patients. AB - OBJECTIVES: To evaluate clinical effectiveness and diagnostic efficiency of a navigation device for MR-guided biopsies of focal liver lesions in a closed-bore scanner. METHODS: In 52 patients, 55 biopsies were performed. An add-on MR navigation system with optical instrument tracking was used for image guidance and biopsy device insertion outside the bore. Fast control imaging allowed visualization of the true needle position at any time. The biopsy workflow and procedure duration were recorded. Histological analysis and clinical course/outcome were used to calculate sensitivity, specificity and diagnostic accuracy. RESULTS: Fifty-four of 55 liver biopsies were performed successfully with the system. No major and four minor complications occurred. Mean tumour size was 23 +/- 14 mm and the skin-to-target length ranged from 22 to 177 mm. In 39 cases, access path was double oblique. Sensitivity, specificity and diagnostic accuracy were 88 %, 100 % and 92 %, respectively. The mean procedure time was 51 +/- 12 min, whereas the puncture itself lasted 16 +/- 6 min. On average, four control scans were taken. CONCLUSIONS: Using this navigation device, biopsies of poorly visible and difficult accessible liver lesions could be performed safely and reliably in a closed-bore MRI scanner. The system can be easily implemented in clinical routine workflow. KEY POINTS: * Targeted liver biopsies could be reliably performed in a closed-bore MRI. * The navigation system allows for image guidance outside of the scanner bore. * Assisted MRI-guided biopsies are helpful for focal lesions with a difficult access. * Successful integration of the method in clinical workflow was shown. * Subsequent system installation in an existing MRI environment is feasible. PMID- 26563350 TI - Dual-Phase Dual-Energy CT in Patients Treated with Erlotinib for Advanced Non Small Cell Lung Cancer: Possible Benefits of Iodine Quantification in Response Assessment. AB - OBJECTIVES: To investigate the relationship of dual-phase dual-energy CT (DE-CT) and tumour size in the evaluation of the response to anti-EGFR therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Dual-phase DE CT was performed in 31 patients with NSCLC before the onset of anti-EGFR (erlotinib) therapy and as follow-up (mean 8 weeks). Iodine uptake (IU; mg/mL) was quantified using prototype software in arterial and venous phases; arterial enhancement fraction (AEF) was calculated. The change of IU before and after therapy onset was compared with anatomical evaluation in maximal transverse diameter and volume (responders vs. non-responders). RESULTS: A significant decrease of IU in venous phase was proved in responders according to all anatomical parameters (p=0.002-0.016). In groups of non-responders, a significant change of IU was not proved with variable trends of development. The most significant change was observed using the anatomical parameter of volume (cut-off 73 %). A significant difference of percentage change in AEF was proved between responding and non-responders (p=0.019-0.043). CONCLUSION: Dual-phase DE-CT with iodine uptake quantification is a feasible method with potential benefit in advanced assessment of anti-EGFR therapy response. We demonstrated a decrease in vascularization in the responding primary tumours and non-significant variable development of vascularization in non-responding tumours. KEY POINTS: * Dual phase DE-CT is feasible for vascularization assessment of NSCLC with anti-EGFR therapy. * There was a significant decrease of iodine uptake in responding tumours. * There was a non-significant and variable development in non-responding tumours. * There was significant difference of AEF percentage change between responders and non-responders. PMID- 26563352 TI - Pelvic pain. PMID- 26563351 TI - Myeloid leukemia factor 1 interfered with Bcl-XL to promote apoptosis and its function was regulated by 14-3-3. AB - Myeloid leukemia factor 1 (MLF1) was involved in t(3;5) chromosomal rearrangement and aberrantly expressed in myelodysplastic syndromes/acute myeloid leukemia patients. Ex vivo experiments showed that the lymphocytes from the Mlf1-deficient mice were more resistant to apoptotic stimulations than the wild-type cells. Furthermore, the ectopically expressed MLF1 induced apoptosis in the cell models. These findings revealed that MLF1 was required for the cells to respond to the apoptotic stimulations. Ex vivo experiments also demonstrated that cytokine withdrawal significantly up-regulated Mlf1's expression and promoted its association with B cell lymphoma-extra large (Bcl-XL) in the lymphocytes, at the same time reduced the association of Bax with Bcl-XL The same effects were also observed in the cells that over-expressed MLF1. However, these effects were observed in Mlf1 null lymphocytes as well as the cells over-expressing Bcl-XL. In addition, MLF1's proapoptosis could be completely prevented by co-expression of Bcl-XL and significantly attenuated in Bax/Bak double null cells. These data, taken together, strongly suggested that in response to the stresses, up-regulated Mlf1 promoted its association with Bcl-XL and reduced the available Bcl-XL for associating with Bax, which resulted in releasing Bax from the Bcl-XL and apoptosis in turn. Lastly, we showed that MLF1 was negatively regulated by 14-3-3 and revealed that 14-3-3 bound to MLF1 and physically blocked MLF1's Bcl-2 homology domain 3 (BH3) as well as Bcl-XL from associating with MLF1. Our findings suggested that ectopically expressed MLF1 could be responsible for the pathological apoptosis in early myelodysplastic syndrome (MDS) patients. PMID- 26563353 TI - Quantifying cognition at the bedside: a novel approach combining cognitive symptoms and signs in HIV. AB - BACKGROUND: Up to half of all people with HIV infection have some degree of cognitive impairment. This impairment is typically mild, but nonetheless often disabling. Although early detection of cognitive impairment offers the greatest hope of effective intervention, there are important barriers to this goal in most clinical settings. These include uncertainty about how self-reported cognitive symptoms relate to objective impairments, and the paucity of bedside measurement tools suitable for mild deficits. Clinicians need guidance in interpreting cognitive symptoms in this population, and a brief cognitive measurement tool targeted to mild impairment. We addressed these two problems together here. The objective of this study was to determine the extent to which performance on cognitive tests and self-reported cognitive symptoms form a unidimensional construct. METHODS: Two hundred three HIV+ individuals completed the Montreal Cognitive Assessment, computerized cognitive tasks and a questionnaire eliciting cognitive symptoms. Rasch measurement theory was applied to determine whether patient-reported and performance items could be combined to measure cognition as a unidimensional latent construct. RESULTS: Performance-based items and cognitive symptoms are arranged hierarchically along the same continuum of cognitive ability, forming a measure with thresholds covering a broad spectrum of ability that has good internal reliability. The cognitive symptoms that fit the measurement model relate to important aspects of everyday life, providing evidence that the identified construct is meaningful. CONCLUSIONS: This finding lays the foundation for a rapid measure of cognitive ability in people with HIV infection that is feasible for routine clinical use, and shows that some cognitive symptoms are systematically related to performance in this population. PMID- 26563354 TI - Melanoma Thickness and Survival Trends in the United States, 1989 to 2009. AB - BACKGROUND: With melanoma incidence rising and mortality stable, some question whether the melanoma epidemic is real. Melanoma thickness and survival trends may provide insights, but previous studies have been limited because of missing data on thickness. METHODS: With a validated imputation method for missing thickness data, we characterized melanoma thickness and survival trends among men and women in the Surveillance, Epidemiology, and End Results (SEER)-9 registries between 1989 and 2009. A total of 98,498 cases of invasive melanoma were identified. All statistical tests were two-sided. RESULTS: Incidence per 100 000 person-years increased (13.94, 95% confidence interval [CI] = 13.65 to 14.23, to 21.87, 95% CI = 21.56 to 22.19, P < .001) between 1989 to 1991 and 2007 to 2009, fatal incidence remained stable (2.32, 95% CI = 2.2 to 2.4, to 2.08, 95% CI = 2.0 to 2.2, P = .20) between 1989 to 1991 and 1998 to 2000, and five-year survival increased (88.29%, 95% CI = 87.60% to 88.95%, to 91.68%, 95% CI = 91.22% to 92.12%, P < .001) between 1989 to 1991 and 2001 to 2003. Increase in incidence occurred across all thickness groups. Median thickness decreased (0.73 to 0.58mm). Geometric mean thickness decreased (0.77 to 0.65mm) 4.6% (95% CI = 4.2% to 5.0%) every three years in multivariable analysis. Thickness decreased among T1/T2 tumors (0.01-1.00 and 1.01-2.00mm) and among all age and sex groups, whites, non-Hispanics, and all body sites. However, thickness increased among T3/T4 tumors (2.01-4.00 and > 4.00mm) and nodular melanomas; acral lentiginous melanomas approached statistical significance. Thickness remained unchanged among some racial minorities. Melanoma-specific survival improved (hazard ratio [HR] = 0.89, 95% CI = 0.88 to 0.91) every three years in multivariable analysis. Improvements in survival occurred across all subgroups except nonblack minorities, and nodular and acral lentiginous subtypes. CONCLUSIONS: Increasing incidence across all thickness groups coupled with T3/T4 lesions becoming thicker suggests that the melanoma epidemic is real and not simply an artifact of increased detection pressure of earlier-stage T1/T2 lesions. Survival is generally improving independent of thickness, but improvements in survival have not been experienced by certain minorities, and nodular and acral lentiginous subtypes. PMID- 26563356 TI - Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib. PMID- 26563355 TI - Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer. AB - In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib. PMID- 26563357 TI - N of 2 Responders with LMNA-NTRK1. PMID- 26563359 TI - [Vitrectomy for retinal proliferation in childhood following hemolytic uremic syndrome]. AB - The formation of retinal membranes can occur due to a variety of reasons but they are most commonly idiopathic due to the aging process. In addition, epiretinal and subretinal membranes can be formed after severe infections. The present case description shows the appearance of a retinal membrane after hemolytic uremic syndrome caused by Shiga toxin positive E. coli. The question arose whether the patient would benefit from vitrectomy with membrane peeling because of the presence of both epiretinal and subretinal gliotic changes. After the operation on the more severely affected right eye a morphological improvement could be achieved so that an operation on the left eye was also recommended. Judging by the course of this case vitrectomy with membrane peeling seems to be a useful instrument even for the simultaneous presence of subretinal and epiretinal membranes. PMID- 26563358 TI - Stemming the Rising Incidence of Melanoma: Calling Prevention to Action. PMID- 26563360 TI - [Bilateral central scotoma in a 28-year-old patient with CADASIL syndrome]. PMID- 26563361 TI - [Preservative-free glaucoma treatment : Selection of the correct treatment in 1 min]. AB - BACKGROUND: The presence of preservatives in topical glaucoma treatments may impact ocular surface function and structure. For treatment to be effective, side effects need to be minimized, in order to promote compliance and allow continuation of therapy. Therefore, in daily clinical practice, it needs to be decided on an individual basis whether a preservative-free treatment is required. OBJECTIVE: This study aimed to develop a questionnaire which helps to quickly and easily identify patients who require preservative-free treatment. MATERIALS AND METHODS: A questionnaire was prepared to collect relevant clinical findings needed to make a therapeutic decision (preservative-free required? Yes/No). Moreover, a rating scheme was developed to enable efficient final assessment of the collected data. To check their practicability in daily clinical practice, both instruments were tested in 11 ophthalmological centers in Germany. RESULTS: The questionnaire and rating scheme were easy to use, integrated efficiently into everyday routine, and performed in about 1 min. Data of 1150 glaucoma patients were collected and preservative-free eyedrops recommended for 586 (51 %). Parameters most frequently associated with such a recommendation were a reduced tear film break-up time of < 10 s (87.5 %) or marked corneal staining (65.5 %). CONCLUSION: The presented approach helps to decide within 1 min, in daily clinical practice, whether preservative-free glaucoma threatment should be recommended. Individualized therapy decisions can thus be made, allowing goal oriented use of preservative-free antiglaucomatosa. This might help to promote compliance and lead to reduced progression of glaucoma. PMID- 26563362 TI - Paediatric imaging radiation dose awareness and use of referral guidelines amongst radiology practitioners and radiographers. AB - OBJECTIVES: The objectives are to investigate radiology practitioners' and radiographers' radiation dose awareness and use of referral guidelines for paediatric imaging examinations. METHODS: A prospective cross-sectional survey was conducted amongst radiology practitioners and radiographers working at a primary paediatric referral centre in Malta. Part of the survey asked participants to indicate the typical effective dose (ED) for several commonly performed paediatric imaging examinations, answer five true-false statements about radiation protection principles, and specify their use of referral guidelines for paediatric imaging. RESULTS: The return of 112 questionnaires provided a response rate of 66.7 %. Overall, imaging practitioners demonstrated poor awareness of radiation doses associated with several paediatric imaging examinations, with only 20 % providing the correct ED estimate for radiation based examinations. Nearly all participants had undertaken radiation protection training, but the type and duration of training undertaken varied. When asked about the use of referral guidelines for paediatric imaging, 77.3 % claimed that they 'did not' or 'were not sure' if they made use of them. CONCLUSIONS: Poor awareness of radiation doses associated with paediatric imaging examinations and the non-use of referral guidelines may impede imaging practitioners' role in the justification and optimisation of paediatric imaging examinations. Education and training activities to address such shortcomings are recommended. KEY POINTS: * Imaging practitioners demonstrated poor radiation dose awareness for 5 paediatric imaging examinations. * Most radiology practitioners and radiographers were 'not sure' or 'did not' use referral guidelines. * Imaging practitioners generally considered previously undertaken paediatric imaging examinations. * Some imaging practitioners had not undertaken training in radiation protection for 10 years. * Training activities to address imaging practitioners' poor radiation dose awareness are encouraged. PMID- 26563364 TI - Margaret McCartney: Disrespecting confidentiality isn't the answer to FGM. PMID- 26563363 TI - Effect of benzalkonium chloride-free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study. AB - BACKGROUND: Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). METHODS: This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan(r) preserved with POLYQUAD(r) [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of <=18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study. RESULTS: All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P < 0.001 for both). A greater percentage of patients achieved a target IOP of <=18 mmHg at week 6 (93.1 %; n = 163/175) and week 12 (93.3 %; n = 166/178) compared with baseline (89.5 %; n = 171/191). There was a 10.5 % increase in the percentage of patients with "none/trace" amounts of hyperemia. Most patients preferred the study medication (81.5 %; n = 141/173) and were confident that they would adhere to their preferred medication (90.8 %; n = 157/173). No serious AEs were reported, and eye irritation (3.7 %; n = 7/191) was the most common treatment-related AE. CONCLUSIONS: Transitioning from BAK containing latanoprost 0.005 % to BAK-free travoprost 0.004 % preserved with PQ reduced IOP in patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01510145. PMID- 26563365 TI - The role of peptidylarginine deiminase 4 in ovarian cancer cell tumorigenesis and invasion. AB - Peptidylarginine deiminase 4 (PADI4) is an enzyme that converts both histone arginine and mono-methyl arginine residues to citrulline, and it has been detected in various subtypes of ovarian cancer. However, the mechanism of action of PADI4 in ovarian carcinogenesis remains unknown. To examine the function of PADI4, we transfected two ovarian cancer cell lines, wild-type p53 A2780 and p53 null SKOV3, with PADI4-siRNA and negative control siRNA. The proliferation of both A2780 and SKOV3 cells decreased significantly following PADI4-siRNA treatment (P A2780 < 0.01; P SKOV3 < 0.001). The invasion and migration ability of A2780 cells also significantly decreased in response to PADI4-siRNA treatment (P < 0.001), but SKOV3 cells showed no such decrease. The apoptotic rate of A2780 cells increased in the presence of PADI4-siRNA, but there was no such increase in SKOV3 cells (P > 0.05). PCR arrays of A2780 cells treated with PADI4-siRNA revealed the up-regulated expression of six genes, including cell death-inducing DFFA-like effector a (CIDEA) and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and the down-regulation of seven genes, including integrin beta 3 (ITGB3) and BCL2-antagonist/killer 1 (BAK1). These results suggest an important role for PADI4 in the p53 pathway and the regulation of the proliferation, apoptosis, invasion and migration of ovarian cancer cells. Our study also demonstrated that PADI4 contributes to tumor metastasis by regulating the gene expression of insulin-like growth factor 1 (IGF1) and WAS/WASL interacting protein family member 1 (WIPF1). PMID- 26563366 TI - STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment. AB - Uterine cervix cancer is the second most common malignancy in women worldwide with human papillomavirus (HPV) as the etiologic factor. The two main histological variants, squamous cell carcinomas (SCC) and adenocarcinomas (AC), resemble the cell morphology of exocervix and endocervix, respectively. Cancer metabolism is a cancer hallmark conditioned by the microenvironment. As uterine cervix homeostasis is dependent on lactate, we hypothesized lactate plays a role in uterine cervix cancer progression. Using in vitro (SiHa-SCC and HeLa-AC) and BALB-c/SCID models, we demonstrated that lactate metabolism is linked to histological types, with SCC predominantly consuming and AC producing lactate. MCT1 is a key factor, allowing lactate consumption and being regulated in vitro by lactate through the FOXM1:STAT3 pathway. In vivo models showed that SCC (SiHa) expresses MCT1 and is dependent on lactate to grow, whereas AC (HeLa) expresses MCT1 and MCT4, with higher growth capacities. Immunohistochemical analysis of tissue microarrays (TMA) from human cervical tumors showed that MCT1 expression associates with the SCC type and metastatic behavior of AC, whereas MCT4 expression concomitantly increases from in situ SCC to invasive SCC and is significantly associated with the AC type. Consistently, FOXM1 expression is statistically associated with MCT1 positivity in SCC, whereas the expression of FOXO3a, a FOXM1 functional antagonist, is linked to MCT1 negativity in AC. Our study reinforces the role of the microenvironment in the metabolic adaptation of cancer cells, showing that cells that retain metabolic features of their normal counterparts are positively selected by the organ's microenvironment and will survive. In particular, MCT1 was shown to be a key element in uterine cervix cancer development; however, further studies are needed to validate MCT1 as a suitable therapeutic target in uterine cervix cancer. PMID- 26563367 TI - Circulating tumor-associated neutrophils (cTAN) contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation. AB - During malignant progression, primary tumors rebuild leukocyte profile and suppress the host anti-tumor immune response. Tumor-associated neutrophils (TAN) increased in the cancer patients and emerged as an important participant and regulator of immune responses. The aim of this study is to investigate the role of circulating TAN (cTAN) in the metastatic process of advanced malignancy. We tested circulating neutrophils from patients (n = 180) with various types of cancer using flow cytometry analyses. We also used B16F10 cell-implanted C57BL/6 tumor-bearing mice model to simulate the advanced malignancy. Peripheral neutrophils were isolated by ficoll density gradient centrifugation, and in vitro tumor-leukocyte co-culture model was used to test tumor cell survival under leukocyte challenge condition. Here, we showed that neutrophils increased in the peripheral blood under the pathological condition of advanced malignancy both in cancer patients and in tumor-bearing mice. In mouse model, the malignantly increased neutrophils were identified as TAN according to the gene transcriptional analyses. We also showed that cTAN enhance tumor metastasis and cTAN could inhibit the activation of the peripheral leukocytes and rescue tumor cells from leukocyte challenge. In conclusion, our finding suggests that the abundance of cTAN in advanced cancer patients contributes to the circulating tumor cell survival by suppressing peripheral leukocyte activation. PMID- 26563368 TI - The involvement of myocyte enhancer factor 2D in regulating tumor biology of cardiac myxoma. AB - The pro-survival transcription factor myocyte enhancer factor 2D (MEF2D) is identified to exhibit pro-tumor effects based on clinical and experimental studies. However, the detailed mechanisms underlying IGF-1-MEF2D pathway-induced tumor biology in cardiac myxoma (CM) was not clear. Here, we investigated the role of MEF2D in CM tissues and cells using RT-PCR, western blot, gene silencing, et al. Our findings revealed MEF2D was significantly increased in CM tissues compared with adjacent normal tissues and closely related to tumor size. In vitro assay demonstrated that IGF-1 enhanced CM cell proliferation in a time-dependent fashion. However, knockdown of MEF2D reversed the IGF-1-induced proliferative effects on CM cells in a time-dependent fashion and further resulted in cell cycle arrest. Based on the molecular level, IGF-1 enhanced the expression of epidermal growth factor receptor (EGFR) and matrix metalloprotein 9 (MMP9) in CM cells, whereas knockdown of MEF2D was able to reduce the expression of EGFR and MMP9 compared with vector control. Furthermore, we found knockdown of MEF2D directly affected G1/S transition in cultured CM cells. In conclusion, MEF2D regulates IGF-1-induced proliferation and apoptosis in CM development, indicating IGF-1-MEF2D pathway may be a useful target for treatment. PMID- 26563369 TI - Involvement of Numb-mediated HIF-1alpha inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells. AB - Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2) that is overexpressed in about 25 % of breast cancer patients. However, primary and/or acquired resistance to trastuzumab develops in most affected persons. In this study, we explored the functional role of miR-182 inhibition with aiming the sensitization of SKBR3 cells to trastuzumab. Cell viability, apoptosis, colony formation, and migration capacities of SKBR3(S) (sensitive) and SKBR3(R) (resistant) cells were assessed to determine the anti proliferative effects of PNA-antimiR-182. In addition, the expression levels of miR-182, mRNA of FOXO1, and Bim as well as the protein levels of HER2 and Notch1 signaling factors were evaluated by stem-loop RT-qPCR, RT-qPCR, and Western blot, respectively. The results indicated that miR-182 might play a causal role in the mechanism of trastuzumab. In line with that, PNA-antimiR-182 inhibited synergistically the viability of both the sensitive and resistant cell groups. Furthermore, the inhibitory effect of PNA-anitmiR-182 on migration in SKBR3 cells was more than the induction of apoptosis. In addition, PNA-antimiR-182 reduced the levels of NICD, Hes1, HIF-1alpha, and p-Akt in both cell groups, while it augmented the intracellular content of FOXO1 and Numb suppressor proteins. In other words, PNA-antimiR-182-mediated upregulation of Numb was associated with downregulation of HIF-1alpha and Hes1. Consequently, downregulation of miR-182 might find therapeutical value for overcoming trastuzumab resistance. Graphical Abstract The crosstalk between HER2 and Notch1 signaling pathway is mediated by miR-182. PMID- 26563370 TI - Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers. AB - Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, beta-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear beta catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 +/- 0.77) with respect to MLG1 (1.26 +/- 0.55) and BL (0.86 +/- 0.52). SHH expression appeared low in BL (1.00 +/- 0.41) and homogenously widespread in MLG1 (1.23 +/- 0.63) and MLG3 (1.56 +/- 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 +/- 0.69 vs 0.82 +/- 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 +/- 0.78) with respect to BL (0.58 +/- 0.55) and MLG1 (1.53 +/- 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon. PMID- 26563371 TI - miR-761 inhibits tumor progression by targeting MSI1 in ovarian carcinoma. AB - Increasing evidences have revealed that microRNAs regulate various biological processes. However, the roles of miR-761 have not been investigated in ovarian cancer. Here, we found that miR-761 expression was significantly lower in ovarian cancer tissues than in their paired noncancerous tissues. Further study revealed that miR-761 overexpression inhibited the ovarian cancer cell proliferation and invasion. Mechanistically, we demonstrated that the oncogenic properties of miR 761 in ovarian cancer were mediated in part by regulating MSI1 expression. miR 761 and MSI1 are inversely expressed in ovarian cancer tissues. In conclusion, we demonstrated that miR-761 repressed ovarian cancer proliferation and invasion by targeting MSI1. PMID- 26563373 TI - Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy. AB - This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects. PMID- 26563372 TI - MicroRNAs, TGF-beta signaling, and the inflammatory microenvironment in cancer. AB - Inflammatory cells and mediators form a major part of the tumor microenvironment and play important roles in the regulation of cancer initiation, tumor cell proliferation, and metastasis. MicroRNAs (miRNAs) play important roles in several physiological and pathological processes, including the regulation of the inflammatory microenvironment in cancer. Transforming growth factor-beta (TGF beta) is an inflammation-related cytokine that functions in both tumor suppression and promotion; however, its underlying molecular mechanisms remain unclear. Recent evidence indicates an association between miRNAs and TGF-beta signaling, providing new insight into the nature of the inflammatory microenvironment in cancer. The present review is an overview of the interaction between miRNAs and inflammatory cytokines, with emphasis on the cross talk between TGF-beta signaling and miRNAs and their influence on cancer cell behavior. The emerging roles of miRNAs in cancer-related inflammation and the potential to target miRNA signaling pathways for cancer therapy are also discussed. PMID- 26563374 TI - Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. AB - Cancers constitutively produce and secrete into the blood and other biofluids 30 150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain. PMID- 26563375 TI - Association and interaction of NFKB1 rs28362491 insertion/deletion ATTG polymorphism and PPP1R13L and CD3EAP related to lung cancer risk in a Chinese population. AB - The nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NFKB1) gene encodes p105 and p50 kD which are both subunits of the transcription factor NF-kB, involved in a wide variety of diseases and pathological states associated with inflammation, immunity, and tumorigenesis. The NFKB1 rs28362491 polymorphism in the promoter region (-94 insertion/deletion ATTG) has been associated with risk of various cancers. Our study aims were to evaluate the associations of NFKB1 rs28362491 polymorphism and interactions of this single-nucleotide polymorphism (SNP) and PPP1R13L and CD3EAP and smoking duration in relation to lung cancer risk in a Chinese population. The study population consisted of 544 Chinese lung cancer cases and 550 cancer-free matched (age, sex, and ethnicity) controls. No associations were found between NFKB1 rs28362491 and lung cancer risk. CD3EAP rs967591 was associated with increased lung cancer risk in the dominant model [OR (95 % CI) = 1.38 (1.05-1.80), P = 0.018]. The common haplotype containing PPP1R13L rs1970764(G), CD3EAP rs967591(A), and CD3EAP rs735482(C) was associated with lung cancer [adjusted OR (95 % CI) = 1.29 (1.03-1.62), P = 0.028]. Multifactor dimensionality reduction (MDR) analysis revealed two-way and three-way interactions between CD3EAP rs735482 and smoking and between NFKB1 rs28362491, PPP1R13L rs1970764, and smoking. In conclusion, we were able to reproduce previously found associations between PPP1R13L and CD3EAP polymorphisms and lung cancer risk in an increased study group, and we found interactions between NFKB1 rs28362491-PPP1R13L rs1970764 and smoking duration and between CD3EAP rs735482 and smoking duration. These results suggest that these genes and smoking are part of the same biological pathway leading to smoking-induced lung cancer. PMID- 26563377 TI - Erratum to: Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma. PMID- 26563376 TI - Association of promoter polymorphisms of Fas -FasL genes with development of Chronic Myeloid Leukemia. AB - Chronic myeloid leukemia (CML) is a monoclonal myeloproliferative disorder of hematopoietic stem cells (HSCs), characterized by reciprocal translocation, leading to the formation of BCR-ABL oncogene with constitutive tyrosine kinase (TK) activity. This oncogene is known to deregulate different downstream pathways which ultimately lead to cell proliferation, defective DNA repair, and inhibition of apoptosis. Fas (Fas cell surface death receptor) is a member of tumor necrosis factor (TNF) superfamily which interacts with its ligand, FasL, to initiate apoptosis. Promoter polymorphisms in Fas-FasL genes are known to influence the apoptotic signaling. Hence, the present study has been aimed to find out the association of the promoter polymorphisms in Fas and FasL genes with the development and progression of CML. Blood samples from 772 subjects (386 controls and 386 cases) were collected and genotyped for Fas-FasL gene polymorphisms through PCR-RFLP method. The association between SNPs and clinical outcome was analyzed using statistical softwares like SPSS version 20, SNPSTATs, and Haploview 2.1. The study revealed a significant association of Fas -670 G>A and FasL -844 T>C polymorphisms with the development of CML while Fas -670 AG was associated with accelerated phase. Combined risk analysis by taking the risk genotypes in cases and controls revealed a significant increase in CML risk with increase in number of risk genotypes (one risk genotype-OR 1.99 (1.44-2.76), p < 0.0001; two risk genotypes-OR 3.33 (1.91-5.81), p < 0.0001). Kaplan-Meier survival analysis of Fas -670 A>G and FasL -844 T>C showed reduced event-free survival in patients carrying the variant genotypes, Fas -670 GG, 32.363 +/- 6.33, and FasL -844 CC, 33.489 +/- 5.83, respectively. Our findings revealed a significant association of Fas -670 GG, FasL -844 TC, and CC genotypes with increased risk of CML. PMID- 26563378 TI - Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function. AB - BACKGROUND AND OBJECTIVES: We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 623 Japanese type 2 diabetic patients with eGFR>=60 ml/min per 1.73 m(2) were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m(2)), and the annual decline rate in eGFR. RESULTS: During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33-2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (-1.3 ml/min per 1.73 m(2)/y; 95% CI, -1.5 to -1.0) was significantly slower than those in the first quartile (-2.2; 95% CI, -2.4 to -1.8). CONCLUSIONS: Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial. PMID- 26563379 TI - Targeting Blood Vessel Stiffness to Protect Kidney Function. PMID- 26563380 TI - Arterial Stiffness and Decline in Kidney Function. AB - BACKGROUND AND OBJECTIVES: The independent link between arterial stiffness and CKD remains unknown. We investigated the association of indicators of arterial stiffness with decline in kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 3666 participants (mean age =65 years old; 58% women) from the Rotterdam Study. Pulse pressure (PP), carotid stiffness, and pulse wave velocity (PWV) were measured. We created genetic risk scores for PP and PWV. Annual declines in kidney function and incident CKD were assessed using eGFR. To put our findings in context of the literature, we performed a meta-analysis of the available population-based studies. RESULTS: After a median (interquartile range) follow-up time of 11 (10.7-11.3) years, 601 participants with incident CKD were recognized. In the model adjusted for age, sex, mean arterial pressure, heart rate, and baseline GFR, each SD higher PP was associated with 0.15-ml/min per 1.73 m(2) steeper annual eGFR decline (95% confidence interval [95% CI], 0.10 to 0.20) and 11% higher risk of incident CKD (95% CI, 1.05 to 1.18). Each SD greater carotid stiffness was associated with 0.08-ml/min per 1.73 m(2) steeper annual eGFR decline (95% CI, 0.04 to 0.13) and 13% higher risk of incident CKD (95% CI, 1.05 to 1.22). Each SD higher PWV was associated with 7% higher risk of incident CKD (95% CI, 1.00 to 1.14). Incorporating our findings in a meta analysis, each SD higher PP and PWV were associated with 16% (95% CI, 1.12 to 1.21) and 8% (95% CI, 1.03 to 1.14) higher risks of incident CKD. Each SD higher PP genetic risk score was associated with 0.06-ml/min per 1.73 m(2) steeper annual eGFR decline (95% CI, 0.01 to 0.10) and 8% higher risk of incident CKD (95% CI, 1.03 to 1.14). There was no association between PWV genetic risk score and kidney function decline. CONCLUSIONS: Higher indices of arterial stiffness are associated with steeper decline in kidney function. This suggests that vascular stiffness could be considered as a target for delaying decline in kidney function. PMID- 26563381 TI - Monitoring of timely and delayed vaccinations: a nation-wide registry-based study of Norwegian children aged < 2 years. AB - BACKGROUND: Delayed vaccinations increase the risk for vaccine preventable diseases (VPDs). Monitoring of delayed vaccinations by using a national immunisation registry has not been studied in countries recommending a two-dose (3 and 5 months of age) primary series of e.g., pertussis vaccine. Surveillance/monitoring of all vaccinations may improve vaccination programmes functioning. METHODS: We obtained information from the Norwegian immunisation registry (SYSVAK) on all programme vaccinations received at age up to 730 days in children born in 2010 (n = 63,382). Timely vaccinations were received up to 7 days after the recommended age. Vaccinations were considered delayed if they were received more than one month after the recommended age in the schedule. RESULTS: In vaccinated children, timely administration of the subsequent three doses of pertussis and one dose of measles occurred in 73.8, 47.6, 53.6 and 43.5 % respectively. Delay for one or more programme vaccinations (diphtheria, tetanus, pertussis, polio, Haemophilus influenza type B, invasive pneumococcal disease, measles, mumps or rubella) was present in 28,336 (44.7 %) children. Among those who were delayed the mean duration was 139 days. The proportion of children that had vaccinations delayed differed among counties (range 37.4 %-57.8 %). Immigrant children were more frequently delayed 52.3 % vs. 43.1 %, RR 1.21 (95 % CI 1.19, 1.24). Children scheduled for vaccines in the summer holiday month (July) were more frequently delayed than others (1(st) dose pertussis vaccine 6.5 % vs. 3.9 % RR 1.65 (95 % CI 1.48, 1.85). Priming against pertussis (2(nd) dose), pneumococcal (2(nd) dose) and measles (1(st) dose) was delayed in 16.8, 18.6 and 29.3 % respectively. CONCLUSION: Vaccinations were frequently delayed. Delayed vaccinations differed among counties and occurred more frequently during the summer vacation (July) and in the immigrant population. Monitoring improves programme surveillance and may be used on an annual basis. PMID- 26563382 TI - Social media could provide early warning of virus outbreaks. PMID- 26563383 TI - Agricultural vulnerability over the Chinese Loess Plateau in response to climate change: Exposure, sensitivity, and adaptive capacity. AB - Understanding how the vulnerability of agricultural production to climate change can differ spatially has practical significance to sustainable management of agricultural systems worldwide. Accordingly, this study developed a conceptual framework to assess the agricultural vulnerability of 243 rural counties on the Chinese Loess Plateau. Indicators representing the climate/agriculture interface were selected to describe exposure and sensitivity, while stocks of certain capitals were used to describe adaptive capacity. A vulnerability index for each county was calculated and the spatial distribution was mapped. Results showed that exposure, sensitivity, and adaptive capacity occur independently, with most contributing indicator values concentrated in a narrow range after normalization. Within the 49 most vulnerable counties, which together encompass 81 % of the vulnerability index range, 42 were characterized by high exposure and sensitivity but low adaptive capacity. The most vulnerable area was found to be located in the central northeast-southwest belt of Loess Plateau. Adaptation measures for both ecological restoration and economic development are needed and potential adaptation options need further investigation. PMID- 26563385 TI - Cancer in ESRD: Clear on the Epidemiology, Hazy on the Mechanisms. PMID- 26563384 TI - Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals. AB - Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention. PMID- 26563386 TI - CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk Patients. AB - Most morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8(+) T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57 expressing CD8(+) T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8(+) T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD57lo) of CD8(+) T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction. PMID- 26563388 TI - Budget cuts have worsened quality of mental healthcare, think tank warns. PMID- 26563387 TI - Surgical treatment of gallbladder carcinoma: a critical review. AB - Gallbladder carcinoma is a relatively uncommon cancer of gastrointestinal (GI) tract. Medical literature is full of nihilistic reports about the treatment of gallbladder carcinoma, especially due to its resistance to current radiotherapeutic or chemotherapeutic treatment modalities and difficult surgical approach for complete resection of these tumors. Herein, we review current diagnostic and therapeutic approaches to this rare GI cancer. PMID- 26563389 TI - The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice. AB - The endocannabinoid system (ECS) is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the beta-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1) signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1) receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS) at 0.1 uM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6) within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight), which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic beta-cell diseases. PMID- 26563390 TI - Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume. AB - In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung disease, in order to fully describe and understand dynamic processes during lung disease onset, progression and therapy. This is highly relevant for the translation of therapy evaluation results from preclinical studies to human patients. PMID- 26563392 TI - Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats. AB - BACKGROUND AND OBJECTIVES: Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. METHODS: The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. RESULTS: The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. CONCLUSION: Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach. PMID- 26563391 TI - Neuroimmunotherapies Targeting T Cells: From Pathophysiology to Therapeutic Applications. AB - Therapeutic options for multiple sclerosis (MS) have significantly increased over the last few years. T lymphocytes are considered to play a central role in initiating and perpetuating the pathological immune response. Currently approved therapies for MS target T lymphocytes, either in an unspecific manner or directly by interference with specific T-cell pathways. While the concept of "T-cell specific therapy" implies specificity and selectivity, currently approved approaches come from a general shaping of the immune system towards anti inflammatory immune responses by non-T-cell-selective immune suppression or immune modulation (e.g., interferons-immune modulation approach) to a depletion of immune cell populations involving T cells (e.g., anti-CD52, alemtuzumab-immune selective depletion approach), or a selective inhibition of distinct molecular pathways in order to sequester leucocytes (e.g., natalizumab-leukocyte sequestration approach). This review will highlight the rationale and results of different T-cell-directed therapeutic approaches coming from basic animal experiments to clinical trials. We will first discuss the pathophysiological rationale for targeting T lymphocytes in MS leading to currently approved treatments acting on T lymphocytes. Furthermore, we will disuss previous promising concepts that have failed to show efficacy in clinical trials or were halted as a result of unexpected adverse events. Learning from the discrepancies between expectations and failures in practical outcomes helps to optimize future research approaches and clinical study designs. As our current view of MS pathogenesis and patient needs is rapidly evolving, novel therapeutic approaches targeting T lymphocytes will also be discussed, including specific molecular interventions such as cytokine-directed treatments or strategies enhancing immunoregulatory mechanisms. Based on clinical experience and novel pathophysiological approaches, T-cell-based strategies will remain a pillarstone of MS therapy. PMID- 26563393 TI - Target selection biases from recent experience transfer across effectors. AB - Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions. PMID- 26563394 TI - Motion influences gaze direction discrimination and disambiguates contradictory luminance cues. AB - In two experiments, we investigated the role of apparent motion in discriminating left/right gaze deviation judgments. We demonstrated that discrimination accuracy and response confidence was significantly higher when the eyes were moved to the left or right, compared to when the eyes were presented in their final shifted position (static images). To dissociate the role of motion signals from luminance signals, gaze stimuli were also presented in reverse contrast. Replicating past studies polarity reversal had a profound and detrimental effect on gaze discrimination in static images, although, intriguingly, while response confidence remained low, participant performance improved as gaze angle increased. In striking contrast to these data, polarity reversal had no negative effect on performance when the eyes were moved. We discuss these findings in the context of a multiple-cue account of gaze perception. PMID- 26563395 TI - The area-of-interest problem in eyetracking research: A noise-robust solution for face and sparse stimuli. AB - A problem in eyetracking research is choosing areas of interest (AOIs): Researchers in the same field often use widely varying AOIs for similar stimuli, making cross-study comparisons difficult or even impossible. Subjective choices while choosing AOIs cause differences in AOI shape, size, and location. On the other hand, not many guidelines for constructing AOIs, or comparisons between AOI production methods, are available. In the present study, we addressed this gap by comparing AOI-production methods in face stimuli, using data collected with infants and adults (with autism spectrum disorder [ASD] and matched controls). Specifically, we report that the attention-attracting and attention-maintaining capacities of AOIs differ between AOI-production methods, and that this matters for statistical comparisons in one of three groups investigated (the ASD group). In addition, we investigated the relation between AOI size and an AOI's attention attracting and attention-maintaining capacities, as well as the consequences for statistical analyses, and report that adopting large AOIs solves the problem of statistical differences between the AOI methods. Finally, we tested AOI production methods for their robustness to noise, and report that large AOIs using the Voronoi tessellation method or the limited-radius Voronoi tessellation method with large radii-are most robust to noise. We conclude that large AOIs are a noise-robust solution in face stimuli and, when implemented using the Voronoi method, are the most objective of the researcher-defined AOIs. Adopting Voronoi AOIs in face-scanning research should allow better between-group and cross-study comparisons. PMID- 26563396 TI - An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats. AB - Continuous spontaneous alternation behavior (SAB) in a Y-maze is used for evaluating working memory in rodents. Here, the design of an automated Y-maze equipped with three infrared optocouplers per arm, and commanded by a reduced instruction set computer (RISC) microcontroller is described. The software was devised for recording only true entries and exits to the arms. Experimental settings are programmed via a keyboard with three buttons and a display. The sequence of arm entries and the time spent in each arm and the neutral zone (NZ) are saved as a text file in a non-volatile memory for later transfer to a USB flash memory. Data files are analyzed with a program developed under LabVIEW(r) environment, and the results are exported to an Excel(r) spreadsheet file. Variables measured are: latency to exit the starting arm, sequence and number of arm entries, number of alternations, alternation percentage, and cumulative times spent in each arm and NZ. The automated Y-maze accurately detected the SAB decrease produced in rats by the muscarinic antagonist trihexyphenidyl, and its reversal by caffeine, having 100 % concordance with the alternation percentages calculated by two trained observers who independently watched videos of the same experiments. Although the values of time spent in the arms and NZ measured by the automated system had small discrepancies with those calculated by the observers, Bland-Altman analysis showed 95 % concordance in three pairs of comparisons, while in one it was 90 %, indicating that this system is a reliable and inexpensive alternative for the study of continuous SAB in rodents. PMID- 26563397 TI - Sensorimotor synchronization: neurophysiological markers of the asynchrony in a finger-tapping task. AB - Sensorimotor synchronization (SMS) is a form of referential behavior in which an action is coordinated with a predictable external stimulus. The neural bases of the synchronization ability remain unknown, even in the simpler, paradigmatic task of finger tapping to a metronome. In this task the subject is instructed to tap in synchrony with a periodic sequence of brief tones, and the time difference between each response and the corresponding stimulus tone (asynchrony) is recorded. We make a step towards the identification of the neurophysiological markers of SMS by recording high-density EEG event-related potentials and the concurrent behavioral response-stimulus asynchronies during an isochronous paced finger-tapping task. Using principal component analysis, we found an asymmetry between the traces for advanced and delayed responses to the stimulus, in accordance with previous behavioral observations from perturbation studies. We also found that the amplitude of the second component encodes the higher-level percept of asynchrony 100 ms after the current stimulus. Furthermore, its amplitude predicts the asynchrony of the next step, past 300 ms from the previous stimulus, independently of the period length. Moreover, the neurophysiological processing of synchronization errors is performed within a fixed-duration interval after the stimulus. Our results suggest that the correction of a large asynchrony in a periodic task and the recovery of synchrony after a perturbation could be driven by similar neural processes. PMID- 26563398 TI - Brain death determination: the imperative for policy and legal initiatives in Sub Saharan Africa. AB - The concept of brain death (BD), defined as irreversible loss of function of the brain including the brainstem, is accepted in the medical literature and in legislative policy worldwide. However, in most of Sub-Saharan Africa (SSA) there are no legal guidelines regarding BD. Hypothetical scenarios based on our collective experience are presented which underscore the consequences of the absence of BD policies in resource-limited countries (RLCs). Barriers to the development of BD laws exist in an RLC such as Kenya. Cultural, ethnic, and religious diversity creates a complex perspective about death challenging the development of uniform guidelines for BD. The history of the medical legal process in the USA provides a potential way forward. Uniform guidelines for legislation at the state level included special consideration for ethnic or religious preferences in specific states. In SSA, medical and social consensus on the definition of BD is a prerequisite for the development BD legislation. Legislative policy will (1) limit prolonged and futile interventions; (2) mitigate the suffering of families; (3) standardise clinical practice; and (4) facilitate better allocation of scarce critical care resources in RLCs. There is a clear-cut need for these policies, and previous successful policies can serve to guide these efforts. PMID- 26563399 TI - A generalized adsorption-phase transition model to describe adsorption rates in flexible metal organic framework RPM3-Zn. AB - Flexible gate-opening metal organic frameworks (GO-MOFs) expand or contract to minimize the overall free energy of the system upon accommodation of an adsorbate. The thermodynamics of the GO process are well described by a number of models, but the kinetics of the process are relatively unexplored. A flexible GO MOF, RPM3-Zn, exhibits a significant induction period for opening by N2 and Ar at low temperatures, both above and below the GO pressure. A similar induction period is not observed for H2 or O2 at comparable pressures and temperatures, suggesting the rate of opening is strongly influenced by the gas-surface interaction rather than an external stress. The induction period leads to severe mass transfer limitations for adsorption and over-prediction of the gate-opening pressure. After review of a number of existing adsorption rate models, we find that none adequately describe the experimental rate data and similar timescales for diffusion and opening invalidate prior reaction-diffusion models. Statistically, the rate data are best described by a compressed exponential function. The resulting fitted parameters exceed the expectations for adsorption but fall within those expected for phase transition. By treating adsorption as a phase transition, we generalize the Avrami theory of phase transition kinetics to describe adsorption in both rigid and flexible hosts. The generalized theory is consistent with observed experimental trends relating to induction period, temperature, pressure, and gas-substrate interaction. PMID- 26563400 TI - Gleason grading challenges in the diagnosis of prostate adenocarcinoma: experience of a single institution. AB - Gleason score (GS) is an important factor in determining management and outcome of prostate adenocarcinoma. A standard GS scheme was introduced by ISUP 2005 consensus conference, but there is still significant discordance in grading prostate adenocarcinomas among pathologists, especially between genitourinary trained (GU) and non-GU pathologists. All biopsies from outside institutions referred for definitive treatment in our hospital are reviewed by a GU pathologist for confirmation and quality assurance. From 2011 to 2013, 117 consecutive prostate consults were retrieved and compared with the initial outside reports as well as final radical prostatectomy (RP) results. Follow-up prostate specific antigen (PSA) was assessed pre- and post-RP, and the results were analyzed. The overall initial GS was higher for all specimens (p = 0.007) especially for the RP cases (p = 0.002). Overall, the modal GS on initial diagnosis was GS7(4 + 3) that was downgraded to the modal GS6(3 + 3) upon review. Despite an overall substantial agreement between the non-GU and GU pathologists [ICC = 0.66], GS by GU pathologist had higher correlation with the final GS in the RP specimen [ICC = 0.62] than non-GU pathologist [ICC = 0.48]. GS on all reviewed cases were found to correlate significantly with the pre-operative PSA (p = 0.002) but the same was not true for the initial report. A non-GU pathologist is more likely to assign a higher GS than a GU pathologist, with a trend to overcall Gleason pattern 4. Considering the implications on treatment, close attention must be paid to the ISUP 2005 consensus conference recommendations. PMID- 26563401 TI - Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus. AB - Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph's free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett's esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05-0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity. PMID- 26563402 TI - Morphological and Chemical Characterization of the Invasive Ants in Hives of Apis mellifera scutellata Lepeletier (Hymenoptera: Apidae). AB - Apiculture in Brazil is quite profitable and has great potential for expansion because of the favorable climate and abundancy of plant diversity. However, the occurrence of pests, diseases, and parasites hinders the growth and profitability of beekeeping. In the interior of the state of Sao Paulo, apiaries are attacked by ants, especially the species Camponotus atriceps (Smith) (Hymenoptera: Formicidae), which use the substances produced by Apis mellifera scutellata (Lepeletier) (Hymenoptera: Apidae), like honey, wax, pollen, and offspring as a source of nourishment for the adult and immature ants, and kill or expel the adult bees during the invasion. This study aimed to understand the invasion of C. atriceps in hives of A. m. scutellata. The individuals were classified into castes and subcastes according to morphometric analyses, and their cuticular chemical compounds were identified using Photoacoustic Fourier transform infrared spectroscopy (FTIR-PAS). The morphometric analyses were able to classify the individuals into reproductive castes (queen and gynes), workers (minor and small ants), and the soldier subcaste (medium and major ants). Identification of cuticular hydrocarbons of these individuals revealed that the eight beehives were invaded by only three colonies of C. atriceps; one of the colonies invaded only one beehive, and the other two colonies underwent a process called sociotomy and were responsible for the invasion of the other seven beehives. The lack of preventive measures and the nocturnal behavior of the ants favored the invasion and attack on the bees. PMID- 26563403 TI - Functional Response of Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) to Aphis gossypii Glover (Hemiptera: Aphididae): Effects of Vermicompost and Host Plant Cultivar. AB - Interactions between natural enemies and herbivores may be affected by application of fertilizers and different cultivars. We investigated the functional response of the predatory gall midge, Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) larvae to the nymphs of the melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), reared on two commonly grown cucumber cultivars in Iran (Khasib and Karim) treated with different vermicompost/soil ratios (0:100, 10:90, 20:80, and 30:70%). Based on logistic regression analysis, A. aphidimyza revealed a type II functional response to the aphid in all treatments. Attack rates and handling times of A. aphidimyza larvae on different vermicompost/soil ratios ranged from 0.076 to 0.140 h(-1) and 0.969 to 1.164 h on Khasib and from 0.092 to 0.123 h(-1) and 0.905 to 1.229 h on Karim, respectively. Furthermore, increasing the density of the melon aphid on both cultivars amended with vermicompost/soil ratios resulted in increased prey consumption by the predator. Density of trichomes increased when plants received higher concentrations of vermicompost. So, trichomes may be responsible for different attack rates and handling times of A. aphidimyza on both cultivars. PMID- 26563405 TI - Effectiveness of rehabilitation in multiple sclerosis relapse on fatigue, self efficacy and physical activity. AB - Relapse of disease is one of the most prominent characteristics of multiple sclerosis. Effectiveness of rehabilitation programmes on fatigue, self-efficacy (SE) and physical activity (PA) has not been investigated so far in context of relapse. The aim of our study was to examine if rehabilitation programme in addition to high-dose methylprednisolone (HDMP) during relapse of disease can influence fatigue, SE and PA more than corticosteroid therapy alone. Patients were randomized in control group receiving only HDMP and experimental group which was in addition included in rehabilitation programme. Outcome measures used were Fatigue Severity Scale (FSS), Multiple Sclerosis Self- Efficacy scale (MSSES), Godin Leisure-Time Exercise Questionnaire (GLTEQ), completed on baseline, 1 and 3 months later. There was no significant change in FSS in both time points, despite different trend seen between groups. The mean MSSES for function and control improved significantly in treatment group after 1 month (807.1 +/- 96.8, p = 0.005; 665.3 +/- 145.1, p = 0.05) and 3 months (820 +/- 83.5, p = 0.004; 720.0 +/ 198.2, p = 0.016.) compared to baseline values. The mean GLTEQ score was significantly higher in the treatment group compared to the control at both follow-up time points (45.7 +/- 7.6, p < 0.001; 34.3 +/- 22.4, p < 0.01). Rehabilitation started along with corticosteroid treatment induced significant improvement in PA compared to HDMP therapy alone. It also influenced noticeable changes in self-efficacy, but effect on fatigue was insufficient. PMID- 26563404 TI - Ectopic transgene expression in the retina of four transgenic mouse lines. AB - Retinal expression of transgenes was examined in four mouse lines. Two constructs were driven by the choline acetyltransferase (ChAT) promoter: green fluorescent protein conjugated to tau protein (tau-GFP) or cytosolic yellow fluorescent protein (YFP) generated through CRE recombinase-induced expression of Rosa26 (ChAT-CRE/Rosa26YFP). Two other constructs targeted inhibitory interneurons: GABAergic horizontal and amacrine cells identified by glutamic acid decarboxylase (GAD65-GFP) or parvalbumin (PV) cells (PV-CRE/Rosa26YFP). Animals were transcardially perfused and retinal sections prepared. Antibodies against PV, calretinin (CALR), calbindin (CALB), and tyrosine hydroxylase (TH) were used to counterstain transgene-expressing cells. In PVxRosa and ChAT-tauGFP constructs, staining appeared in vertically oriented row of processes resembling Muller cells. In the ChATxRosa construct, populations of amacrine cells and neurons in the ganglion cell layer were labeled. Some cones also exhibited GFP fluorescence. CALR, PV and TH were found in none of these cells. Occasionally, we found GFP/CALR and GFP/PV double-stained cells in the ganglion cell layer (GCL). In the GAD65-GFP construct, all layers of the neuroretina were labeled, except photoreceptors. Not all horizontal cells expressed GFP. We did not find GFP/TH double-labeled cells and GFP was rarely present in CALR- and CALB-containing cells. Many PV-positive neurons were also labeled for GFP, including small diameter amacrines. In the GCL, single labeling for GFP and PV was ascertained, as well as several CALR/PV double-stained neurons. In the GCL, cells triple labeled with GFP/CALR/CALB were sparse. In conclusion, only one of the four transgenic constructs exhibited an expression pattern consistent with endogenous retinal protein expression, while the others strongly suggested ectopic gene expression. PMID- 26563406 TI - Facial palsy in cerebral venous thrombosis: an atypical case in adults. PMID- 26563407 TI - Intravenous theophylline rapidly decreases post-lumbar puncture headaches. AB - When managing therapy for the post-lumbar puncture headaches (PLPHs), an efficacious, fast-acting, practical and safe method is preferred. Invasive methods have known complications and oral medications might be problematic when nausea and vomiting occurs with severe headaches. The aim of this study was to highlight the brief initial time for a remarkable decrease of PLPH pain levels after the administration of IV theophylline infusion. We observed that IV theophylline infusion has a rapid and marked effect on decreasing pain in PLPHs. At 30 min of theophylline infusion, mean VAS levels were decreased by 47.1 % and at 60 min of infusion, the decrease of pain was 61.9 %. We conclude that IV theophylline infusion is a rapidly effective, noninvasive, practical and low-cost way to treat PLPHs. To the best of our knowledge, this is the first study to highlight both the efficacy and the speed of the effect of pain relief in PLPHs. PMID- 26563408 TI - Restless legs syndrome is associated with poor sleep quality and quality of life in patients with ankylosing spondylitis: a questionnaire-based study. AB - We aimed to investigate the frequency of restless legs syndrome (RLS) and the associations between RLS and quality of sleep and life in patients with ankylosing spondylitis (AS). One hundred and eight AS patients and 64 controls were included in this study. Demographics, clinical, and laboratory data were recorded. The presence of RLS was determined with face-to-face interview by an experienced neurologist based on the International RLS Study Group criteria. RLS severity was evaluated using International RLS Study Group rating scale. Sleep quality and insomnia severity were assessed by Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI), respectively. Disease-related quality of life was evaluated by AS quality of life questionnaire (ASQoL). The frequency of RLS was significantly higher in AS patients than in controls (36.4 vs. 14.0 %, p = 0.004). RLS severity score for AS patients was significantly higher than that for controls (p = 0.03). The AS patients had higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication domains of PSQI, and also total PSQI and ISI than controls (p < 0.05, for all). ASQoL scores were higher in AS patients with RLS compared to those without RLS (p < 0.001). RLS severity was observed to be independently associated with total PSQI, ISI and ASQoL (p < 0.05, for all). As RLS may adversely affect the sleep and quality of life in AS patients, clinicians should be aware of RLS for early diagnosis and management in AS patients. PMID- 26563409 TI - Rhenium tetrazolato complexes coordinated to thioalkyl-functionalised phenanthroline ligands: synthesis, photophysical characterisation, and incubation in live HeLa cells. AB - Three new complexes of formulation fac-[Re(CO)3(diim)L], where diim is either 1,10-phenanthroline or 1,10-phenanthroline functionalised at position 5 by a thioalkyl chain, and L is either a chloro or aryltetrazolato ancillary ligand, were synthesised and photophysically characterised. The complexes exhibit phosphorescent emission with maxima around 600 nm, originating from triplet metal to-ligand charge transfer states with partially mixed ligand-to-ligand charge transfer character. The emission is relatively long-lived, within the 200-400 ns range, and with quantum yields of 2-4%. The complexes were trialed as cellular markers in live HeLa cells, along with two previously reported rhenium tetrazolato complexes bound to unsubstituted 1,10-phenanthroline. All five complexes exhibit good cellular uptake and non-specific perinuclear localisation. Upon excitation at 405 nm, the emission from the rhenium complexes could be clearly distinguished from autofluorescence, as demonstrated by spectral detection within the live cells. Four of the complexes did not appear to be toxic, however prolonged excitation could result in membrane blebbing. No major sign of photobleaching was detected upon multiple imaging on the same cell sample. PMID- 26563410 TI - Burkholderia pseudomallei induces IL-23 production in primary human monocytes. AB - Burkholderia pseudomallei, a gram-negative intracellular bacterium, is a causative agent of melioidosis. The bacterium has been shown to induce the innate immune response, particularly pro-inflammatory cytokine production in several of both mouse and human cell types. In the present study, we investigate host immune response in B. pseudomallei-infected primary human monocytes. We discover that wild-type B. pseudomallei is able to survive and multiply inside the primary human monocytes. In contrast, B. pseudomallei LPS mutant, a less virulent strain, is susceptible to host killing during bacterial infection. Moreover, microarray result showed that wild-type B. pseudomallei but not B. pseudomallei LPS mutant is able to activate gene expression of IL-23 as demonstrated by the up-regulation of p19 and p40 subunit expression. Consistent with gene expression analysis, the secretion of IL-23 analyzed by ELISA also showed that wild-type B. pseudomallei induces a significantly higher level of IL-23 secretion than that of B. pseudomallei LPS mutant. These results implied that IL-23 may be an important cytokine for the innate immune response during B. pseudomallei infection. The regulation of IL-23 production may drive the different host innate immune responses between patients and may relate to the severity of melioidosis. PMID- 26563411 TI - Safety and Efficacy of Left Atrial Appendage Closure with the Amplatzer Cardiac Plug in Very High Stroke and Bleeding Risk Patients with Non-Valvular Atrial Fibrillation. AB - INTRODUCTION: Limited data exist on the outcomes after left atrial appendage closure (LAAC) with the AmplatzerTM Cardiac Plug (ACP; St. Jude Medical, Minneapolis, MN, USA) in patients with atrial fibrillation (AF) with very high stroke and bleeding risks, the subset expected to benefit most from this procedure. The objective of this study was to report clinical outcomes after LAAC with the ACP device in a very high stroke and bleeding risk cohort of patients with non-valvular AF and contraindications to oral anticoagulation (OAC). METHODS: LAAC using the ACP device was performed in 96 patients with AF who had median CHA2DS2-VASc and HAS-BLED scores of 5 and 3, respectively. Post-procedure, patients received dual antiplatelet therapy for 6 months. A transesophageal echocardiography (TEE) was scheduled at 6 months. RESULTS: Procedural success was 100%. Procedural-related complications occurred in 7.3% (pericardial effusion, 4.2%; thromboembolic events, 2.1%; device embolization, 1.0%). Additional thromboembolic events occurred in three patients during follow-up (92.7% follow up). After 93.4 patient-years of follow-up, the annual rates of thromboembolic and major bleeding events were 3.2% and 1.1%, respectively. In those with TEE follow-up (70%), complete LAAC with no leaks was observed. Thrombus formation on the device was noted on TEE in two patients. CONCLUSION: LAAC using the ACP device was associated with an acceptable low rate of embolic and bleeding events after a median follow-up of 9 months in a cohort of patients with AF who were amongst the highest stroke and bleeding risks reported so far in LAAC trials. PMID- 26563412 TI - User-friendly aerobic reductive alkylation of iridium(III) porphyrin chloride with potassium hydroxide: scope and mechanism. AB - Alkylation of iridium 5,10,15,20-tetrakistolylporphyrinato carbonyl chloride, Ir(ttp)Cl(CO) (1), with 1 degrees , 2 degrees alkyl halides was achieved to give (ttp)Ir-alkyls in good yields under air and water compatible conditions by utilizing KOH as the cheap reducing agent. The reaction rate followed the order: RCl < RBr < RI (R = alkyl), and suggests an SN2 pathway by [Ir(I)(ttp)](-). Ir(ttp)-adamantyl was obtained under N2 when 1-bromoadamantane was utilized, which could only undergo bromine atom transfer pathway. Mechanistic investigations reveal a substrate dependent pathway of SN2 or halogen atom transfer. PMID- 26563413 TI - Community-Level Physiological Profiling of Microbial Communities in Constructed Wetlands: Effects of Sample Preparation. AB - Community-level physiological profiling (CLPP) using BIOLOG(r) EcoPlatesTM has become a popular method for characterizing and comparing the functional diversity, functional potential, and metabolic activity of heterotrophic microbial communities. The method was originally developed for profiling soil communities; however, its usage has expanded into the fields of ecotoxicology, agronomy, and the monitoring and profiling of microbial communities in various wastewater treatment systems, including constructed wetlands for water pollution control. When performing CLPP on aqueous samples from constructed wetlands, a wide variety of sample characteristics can be encountered and challenges may arise due to excessive solids, color, or turbidity. The aim of this study was to investigate the impacts of different sample preparation methods on CLPP performed on a variety of aqueous samples covering a broad range of physical and chemical characteristics. The results show that using filter paper, centrifugation, or settling helped clarify samples for subsequent CLPP analysis, however did not do so as effectively as dilution for the darkest samples. Dilution was able to provide suitable clarity for the darkest samples; however, 100-fold dilution significantly affected the carbon source utilization patterns (CSUPs), particularly with samples that were already partially or fully clear. Ten-fold dilution also had some effect on the CSUPs of samples which were originally clear; however, the effect was minimal. Based on these findings, for this specific set of samples, a 10-fold dilution provided a good balance between ease of use, sufficient clarity (for dark samples), and limited effect on CSUPs. The process and findings outlined here can hopefully serve future studies looking to utilize CLPP for functional analysis of microbial communities and also assist in comparing data from studies where different sample preparation methods were utilized. PMID- 26563414 TI - Myocardial infarction: stem cell transplantation for cardiac regeneration. AB - It is estimated that by 2030, almost 23.6 million people will perish from cardiovascular disease, according to the WHO. The review discusses advances in stem cell therapy for myocardial infarction, including cell sources, methods of differentiation, expansion selection and their route of delivery. Skeletal muscle cells, hematopoietic cells and mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs)-derived cardiomyocytes have advanced to the clinical stage, while induced pluripotent cells (iPSCs) are yet to be considered clinically. Delivery of cells to the sites of injury and their subsequent retention is a major issue. The development of supportive scaffold matrices to facilitate stem cell retention and differentiation are analyzed. The review outlines clinical translation of conjugate stem cell-based cellular therapeutics post-myocardial infarction. PMID- 26563415 TI - The mating-type locus b of the sugarcane smut Sporisorium scitamineum is essential for mating, filamentous growth and pathogenicity. AB - Sporisorium scitamineum is the causal agent of sugarcane smut, which is one of the most serious constraints to global sugarcane production. S. scitamineum and Ustilago maydis are two closely related smut fungi, that are predicted to harbor similar sexual mating processes/system. To elucidate the molecular basis of sexual mating in S. scitamineum, we identified and deleted the ortholog of mating specific U. maydis locus b, in S. scitamineum. The resultant b-deletion mutant was defective in mating and pathogenicity in S. scitamineum. Furthermore, a functional b locus heterodimer could trigger filamentous growth without mating in S. scitamineum, and functionally replace the b locus in U. maydis in terms of triggering aerial filament production and forming solopathogenic strains, which do not require sexual mating prior to pathogenicity on the host plants. PMID- 26563416 TI - Functional roles of a predicted branched chain aminotransferase encoded by the LkBAT1 gene of the yeast Lachancea kluyveri. AB - Branched chain amino acid aminotransferases (BCATs) catalyze the last step of the biosynthesis and the first step of the catabolism of branched chain amino acids. In Saccharomyces cerevisiae, BCATs are encoded by the ScBAT1 and ScBAT2 paralogous genes. Analysis of Lachancea kluyveri genome sequence, allowed the identification of the LkBAT1 locus, which could presumably encode a BCAT. A second unlinked locus (LkBAT1bis), exhibiting sequence similarity to LkBAT1 was also identified. To determine the function of these putative BCATs, L. kluyveri mutant strains lacking LkBAT1, LkBAT1bis or both genes were generated and tested for VIL metabolism. LkBat1 displayed branched chain aminotransferase activity and is required for VIL biosynthesis and catabolism. However, Lkbat1Delta mutant is a valine and isoleucine auxotroph and a leucine bradytroph indicating that L. kluyveri harbors an alternative enzyme(s) involved in leucine biosynthesis. Additionally, heterologous reciprocal gene complementation between S. cerevisiae and L. kluyveri orthologous LkBAT1, ScBAT1 and ScBAT2 genes, confirmed that the mitochondrial LkBat1 functions as BCAT in S. cerevisiae, restoring wild type phenotype to the ScBAT1 null mutant. Conversely, LkBAT1bis did not display a role in BCAAs metabolism. However, when ethanol was used as carbon source, deletion of LkBAT1bis in an Lkbat1Delta null strain resulted in an extended 'lag' growth phase, pointing to a potential function of LkBAT1 and LkBAT1bis in the aerobic metabolism of L. kluyveri. These results confirm the BCAT function of LkBAT1 in L. kluyveri, and further support the proposition that the BCAT function in ancestral-type yeasts has been distributed in the two paralogous genes present in S. cerevisiae. PMID- 26563418 TI - Compensating for population sampling in simulations of epidemic spread on temporal contact networks. AB - Data describing human interactions often suffer from incomplete sampling of the underlying population. As a consequence, the study of contagion processes using data-driven models can lead to a severe underestimation of the epidemic risk. Here we present a systematic method to alleviate this issue and obtain a better estimation of the risk in the context of epidemic models informed by high resolution time-resolved contact data. We consider several such data sets collected in various contexts and perform controlled resampling experiments. We show how the statistical information contained in the resampled data can be used to build a series of surrogate versions of the unknown contacts. We simulate epidemic processes on the resulting reconstructed data sets and show that it is possible to obtain good estimates of the outcome of simulations performed using the complete data set. We discuss limitations and potential improvements of our method. PMID- 26563417 TI - Isolation and Potential for Transmission of Mycobacterium bovis at Human livestock-wildlife Interface of the Serengeti Ecosystem, Northern Tanzania. AB - Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), is a multihost pathogen of public health and veterinary importance. We characterized the M. bovis isolated at the human-livestock-wildlife interface of the Serengeti ecosystem to determine the epidemiology and risk of cross-species transmission between interacting hosts species. DNA was extracted from mycobacterial cultures obtained from sputum samples of 472 tuberculosis (TB) suspected patients and tissue samples from 606 livestock and wild animal species. M. bovis isolates were characterized using spoligotyping and Mycobacterial Interspersed Repetitive Units Variable Tandem Repeats (MIRU-VNTR) on 24 loci. Only 5 M. bovis were isolated from the cultured samples. Spoligotyping results revealed that three M. bovis isolates from two buffaloes (Syncerus caffer) and 1 African civet (Civettictis civetta) belonged to SB0133 spoligotype. The two novel strains (AR1 and AR2) assigned as spoligotype SB2290 and SB2289, respectively, were identified from indigenous cattle (Bos indicus). No M. bovis was detected from patients with clinical signs consistent with TB. Of the 606 animal tissue specimens and sputa of 472 TB-suspected patients 43 (7.09%) and 12 (2.9%), respectively, yielded non tuberculous mycobacteria (NTM), of which 20 isolates were M. intracellulare. No M. avium was identified. M. bovis isolates from wildlife had 45.2% and 96.8% spoligotype pattern agreement with AR1 and AR2 strains, respectively. This finding indicates that bTB infections in wild animals and cattle were epidemiologically related. Of the 24 MIRU-VNTR loci, QUB 11b showed the highest discrimination among the M. bovis strains. The novel strains obtained in this study have not been previously reported in the area, but no clear evidence for recent cross-species transmission of M. bovis was found between human, livestock and wild animals. PMID- 26563419 TI - In Vitro Selective Anti-Proliferative Effect of Zinc Oxide Nanoparticles Against Co-Cultured C2C12 Myoblastoma Cancer and 3T3-L1 Normal Cells. AB - The zinc oxide (ZnO) nanoparticle has been widely used in biomedical applications and cancer therapy and has been reported to induce a selective cytotoxic effect on cancer cell proliferation. The present study investigated the cytotoxicity of ZnO nanoparticles against co-cultured C2C12 myoblastoma cancer cells and 3T3-L1 adipocytes. Our results showed that the ZnO nanoparticles could be cytotoxic to C2C12 myoblastoma cancer cells than 3T3-L1 cells. The messenger RNA (mRNA) expressions of p53 and bax were significantly increased 114.3 and 118.2 % in the C2C12 cells, whereas 42.5 and 40 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was reduced 38.2 and 28.5 % in the C2C12 and 3T3-L1 cells, respectively, whereas the mRNA expression of caspase-3 was increased 80.7 and 51.6 % in the C2C12 and 3T3-L1 cells, respectively. The protein expressions of p53, bax, and caspase-3 were significantly increased 40, 81.8, and 80 % in C2C12 cells, whereas 20.3, 28.2, and 37.9 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was significantly reduced 32.2 and 22.7 % in C2C12 and 3T3-L1 cells, respectively. Caspase-3 enzyme activity and reactive oxygen species (ROS) were increased in co-cultured C2C12 cells compared to 3T3-L1 cells. Taking all these data together, it may suggest that ZnO nanoparticles severely induce apoptosis in C2C12 myoblastoma cancer cells than 3T3-L1 cells. PMID- 26563420 TI - Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain. AB - Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity. PMID- 26563421 TI - Using the cost-effectiveness of allogeneic islet transplantation to inform induced pluripotent stem cell-derived beta-cell therapy reimbursement. AB - AIMS: In the present study a cost-effectiveness analysis of allogeneic islet transplantation was performed and the financial feasibility of a human induced pluripotent stem cell-derived beta-cell therapy was explored. METHODS: Previously published cost and health benefit data for islet transplantation were utilized to perform the cost-effectiveness and sensitivity analyses. RESULTS & CONCLUSION: It was determined that, over a 9-year time horizon, islet transplantation would become cost saving and 'dominate' the comparator. Over a 20-year time horizon, islet transplantation would incur significant cost savings over the comparator (GBL59,000). Finally, assuming a similar cost of goods to islet transplantation and a lack of requirement for immunosuppression, a human induced pluripotent stem cell-derived beta-cell therapy would dominate the comparator over an 8-year time horizon. PMID- 26563422 TI - Glycosylated Alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker. AB - Presently existing screening approaches for lung cancer are not being proving sufficient and sensitive, so a study was conducted to identify disease related biomarker proteins for diagnostic applications. A total of 100 lung cancer patients (88 non-small cell lung cancer and 12 small cell lung cancer) and 50 healthy controls were included in this study. Serum samples of patients and healthy controls were subjected to a series of proteomic approaches and as a result of two dimensional gel electrophoresis, a ~ 43 kDa protein was found to be differentially expressed compared to healthy controls. Quantitative profiling of two dimensional gels by Dymension software analysis displayed 3.58 fold increased expression of ~ 43 kDa protein in squamous cell carcinoma and 2.92 fold in case of adenocarcinoma. Mass spectrometric analysis resulted in identification of 8 differentially expressed proteins, out of which human Alpha-1-acid glycoprotein 1 was targeted for further validations. This candidate protein exhibited N-linked glycosylation at five amino acid residues; 33, 56, 72, 93, and 103 with significant score of 0.66, 0.78, 0.78, 0.53 and 0.66, respectively. Sandwich ELISA quantified high serum levels of Alpha-1-acid glycoprotein 1 in squamous cell carcinoma (2.93 g/l +/- 1.22) and adenocarcinoma (2.39 g/l +/- 1.13) when compared with healthy controls (0.83 g/l +/- 0.21). One-way ANOVA analysis predicted highly significant variation of Alpha-1-acid glycoprotein 1, among all the study types (F-value 65.37, p-value 0.000). This study may prove as a non invasive, cost effective and sensitive scheme for diagnosis of lung cancer, by passing the expensive and painful screening procedures. PMID- 26563423 TI - Sialic acid-dependent cell entry of human enterovirus D68. AB - Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry. PMID- 26563424 TI - Transplantation of three-dimensional artificial human vascular tissues fabricated using an extracellular matrix nanofilm-based cell-accumulation technique. AB - We have established a novel three-dimensional (3D) tissue-constructing technique, referred to as the 'cell-accumulation method', which is based on the self assembly of cultured human cells. In this technique, cells are coated with fibronectin and gelatin to construct extracellular matrix (ECM) nanofilms and cultured to form multi-layers in vitro. By using this method, we have successfully fabricated artificial tissues with vascular networks constructed by co-cultivation of human umbilical vein-derived vascular endothelial cells between multi-layers of normal human dermal fibroblasts. In this study, to assess these engineered vascular tissues as therapeutic implants, we transplanted the 3D human tissues with microvascular networks, fabricated based on the cell-accumulation method, onto the back skin of nude mice. After the transplantation, we found vascular networks with perfusion of blood in the transplanted graft. At the boundary between host and implanted tissue, connectivity between murine and human vessels was found. Transmission electron microscopy of the implanted artificial vascular tubules demonstrated the ultrastructural features of blood capillaries. Moreover, maturation of the vascular tissues after transplantation was shown by the presence of pericyte-like cells and abundant collagen fibrils in the ECM surrounding the vasculature. These results demonstrated that artificial human vascular tissues constructed by our method were engrafted and matured in animal skin. In addition, the implanted artificial human vascular networks were connected with the host circulatory system by anastomosis. This method is an attractive technique for engineering prevascularized artificial tissues for transplantation. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26563425 TI - Development of an ex vivo breast cancer lung colonization model utilizing a decellularized lung matrix. AB - The metastatic spread of cancer cells to distant sites represents the major cause of cancer-related deaths in breast cancer patients, and lungs are one of the most common sites for metastatic colonization. Developing a physiologically relevant tissue culture model to mimic lung colonization of breast cancer is crucial for the investigation of the biology of cancer metastasis and evaluation of drug treatment efficacy. Here, we describe an ex vivo lung colonization assay for breast cancer using the native three-dimensional (3D) lung extracellular matrix. The native matrix was isolated from murine lungs using a decellularization technique, and the preservation of extracellular matrix (ECM) composition, integrity and mechanical properties was confirmed. We showed that metastatic MDA MB 231 and 4T1 cells invaded and colonized in the decellularized lung matrix, whereas only a small mass of non-metastatic MCF7 cells survived under the same condition. Furthermore, knockdown of ZEB1, an epithelial-mesenchymal transition (EMT) inducer, significantly reduced invasion and colonization of MDA-MB 231 cells in the decellularized lung, suggesting an important role of EMT in breast cancer metastasis. We conclude that the decellularized lung retains the biophysical and biochemical properties of the lung ECM and provides a powerful tool to investigate the lung colonization of breast cancer. PMID- 26563426 TI - Bioengineered Human Pyloric Sphincters Using Autologous Smooth Muscle and Neural Progenitor Cells. AB - Gastroparesis leads to inadequate emptying of the stomach resulting in severe negative health impacts. Appropriate long-term treatments for these diseases may require pyloric sphincter tissue replacements that possess functional smooth muscle cell (SMC) and neural components. This study aims to bioengineer, for the first time, innervated human pylorus constructs utilizing autologous human pyloric sphincter SMCs and human neural progenitor cells (NPCs). Autologous SMCs and NPCs were cocultured in dual-layered hydrogels and formed concentrically aligned pylorus constructs. Innervated autologous human pylorus constructs were characterized through biochemical and physiologic assays to assess the phenotype and functionality of SMCs and neurons. SMCs within bioengineered human pylorus constructs displayed a tonic contractile phenotype and maintained circumferential alignment. Neural differentiation within bioengineered constructs was verified by positive expression of betaIII-tubulin, neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT). Autologous bioengineered innervated human pylorus constructs generated a robust spontaneous basal tone and contracted in response to potassium chloride (KCl). Contraction in response to exogenous neurotransmitter acetylcholine (ACh), relaxation in response to vasoactive intestinal peptide (VIP), and electrical field stimulation (EFS) were also observed. Neural network integrity was demonstrated by inhibition of EFS-induced relaxation in the presence of a neurotoxin or nNOS inhibitors. Partial inhibition of ACh-induced contraction and VIP-induced relaxation following neurotoxin treatment was observed. These studies provide a proof of concept for bioengineering functional innervated autologous human pyloric sphincter constructs that generate a robust basal tone and contain circumferentially aligned SMCs, which display a tonic contractile phenotype and functional differentiated neurons. These autologous constructs have the potential to be used as (1) functional replacement organs and (2) physiologically relevant models to investigate human pyloric sphincter disorders. PMID- 26563427 TI - A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly. AB - We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debre Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. WHAT IS KNOWN: * Mutations in BCS1L cause mitochondrial complex III deficiencies. * Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: * Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debre-Fanconi-type tubulopathy. * The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon. PMID- 26563428 TI - Smart materials: in situ gel-forming systems for nasal delivery. AB - In the last decade in situ gelling systems have emerged as a novel approach in intranasal delivery of therapeutics, capturing the interest of scientific community. Considerable advances have been currently made in the development of novel formulations containing both natural and synthetic polymers. In this paper we present recent developments on in situ gelling systems for nasal delivery, highlighting the mechanisms that govern their formation. PMID- 26563429 TI - Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6. AB - Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Biochemical and genetic approaches have identified a set of factors involved in microvilli formation; however, the underlying extrinsic regulatory mechanism of microvilli formation remains largely unknown. Here we demonstrate that fluid shear stress (FSS), an external mechanical cue, serves as a trigger for microvilli formation in human placental trophoblastic cells. We further reveal that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel plays a critical role in flow-induced Ca(2+) influx and microvilli formation. TRPV6 regulates phosphorylation of Ezrin via a Ca(2+)-dependent phosphorylation of Akt; this molecular event is necessary for microvillar localization of Ezrin in response to FSS. Our findings provide molecular insight into the microvilli-mediated mechanoresponsive cellular functions, such as epithelial absorption, signal perception and mechanotransduction. PMID- 26563430 TI - Correlations of microRNA:microRNA expression patterns reveal insights into microRNA clusters and global microRNA expression patterns. AB - MicroiRNAs are genome encoded small double stranded RNAs that regulate expression of homologous mRNAs. With approximately 2500 human miRNAs and each having hundreds of potential mRNA targets, miRNA based gene regulation is quite pervasive in both development and disease. While there are numerous studies investigating miRNA:mRNA and miRNA:protein target expression correlations, there are relatively few studies of miRNA:miRNA co-expression. Here we report on our analysis of miRNA:miRNA co-expression using expression data from the miRNA expression atlas of Landgraf et al. Our analysis indicates that many, but not all, genomically clustered miRNAs are co-expressed as a single pri-miRNA transcript. We have also identified co-expression groups that have similar biological activity. Further, the non-correlative miRNAs we have uncovered have been shown to be of utility in establishing miRNA biomarkers and signatures for certain tumours and cancers. PMID- 26563431 TI - The Impact of Prestretch Induced Surface Anisotropy on Axon Regeneration. AB - Nerve regeneration after spinal cord injury requires proper axon alignment to bridge the lesion site and myelination to achieve functional recovery. Significant effort has been invested in developing engineering approaches to induce axon alignment with less focus on myelination. Topological features, such as aligned fibers and channels, have been shown to induce axon alignment, but do not enhance axon thickness. We previously demonstrated that surface anisotropy generated through mechanical prestretch induced mesenchymal stem cells to align in the direction of prestretch. In this study, we demonstrate that static prestretch-induced anisotropy promotes dorsal root ganglion (DRG) neurons to extend thicker axon aggregates along the stretched direction and form aligned fascicular-like axon tracts. Moreover, Schwann cells, when cocultured with DRG neurons on the prestretched surface colocalized with the aligned axons and expressed P0 protein, are indicative of myelination of the aligned axons, thereby demonstrating that prestretch-induced surface anisotropy is beneficial in enhancing axon alignment, growth, and myelination. PMID- 26563432 TI - Growing rod technique for the treatment of the traumatic spinopelvic dissociation: a technical trick. AB - BACKGROUND CONTEXT: Traumatic spinopelvic dissociation, sometimes referred to as U-shaped sacral fracture, is a very rare high-energy trauma. The surgical management of spinopelvic dissociation includes decompression, reduction, and fixation. PURPOSE: We report a novel surgical technique for the treatment of spinopelvic dissociation that uses growing rods and a pedicle screw system, which is often used to treat patients with early onset scoliosis. STUDY DESIGN: This case report used a technical report of spinopelvic dissociation surgery using spinopelvic fixation and the growing rod technique. PATIENT SAMPLE: One case was used as the patient sample. OUTCOME MEASURE: Radiographic outcomes, including plain X-ray, three-dimensional computed tomography, and magnetic resonance imaging scan were the outcome measures. METHODS: The radiographic outcomes were compared preoperatively, postoperatively, and at the 1-year follow-up with bony union. RESULTS: Growing techniques improved traumatic sacral angulation, displacement, and canal encroachment, and provided sufficient structural support. CONCLUSION: The growing rod technique for spinopelvic dissociation under intraoperative neurophysiological monitoring could be a useful alternative surgical option, especially in patients without neurologic deficit. PMID- 26563433 TI - Evolution of the KCS gene family in plants: the history of gene duplication, sub/neofunctionalization and redundancy. AB - Very long-chain fatty acids (VLCFAs) play an important role in the survival and development of plants, and VLCFA synthesis is regulated by beta-ketoacyl-CoA synthases (KCSs), which catalyze the condensation of an acyl-CoA with malonyl CoA. Here, we present a genome-wide survey of the genes encoding these enzymes, KCS genes, in 28 species (26 genomes and two transcriptomes), which represents a large phylogenetic scale, and also reconstruct the evolutionary history of this gene family. KCS genes were initially single-copy genes in the green plant lineage; duplication resulted in five ancestral copies in land plants, forming five fundamental monophyletic groups in the phylogenetic tree. Subsequently, KCS genes duplicated to generate 11 genes of angiosperm origin, expanding up to 20-30 members in further-diverged angiosperm species. During this process, tandem duplications had only a small contribution, whereas polyploidy events and large scale segmental duplications appear to be the main driving force. Accompanying this expansion were variations that led to the sub- and neofunctionalization of different members, resulting in specificity that is likely determined by the 3-D protein structure. Novel functions involved in other physiological processes emerged as well, though redundancy is also observed, largely among recent duplications. Conserved sites and variable sites of KCS proteins are also identified by statistical analysis. The variable sites are likely to be involved in the emergence of product specificity and catalytic power, and conserved sites are possibly responsible for the preservation of fundamental function. PMID- 26563435 TI - Bird embryos uncover homology and evolution of the dinosaur ankle. AB - The anklebone (astragalus) of dinosaurs presents a characteristic upward projection, the 'ascending process' (ASC). The ASC is present in modern birds, but develops a separate ossification centre, and projects from the calcaneum in most species. These differences have been argued to make it non-comparable to dinosaurs. We studied ASC development in six different orders of birds using traditional techniques and spin-disc microscopy for whole-mount immunofluorescence. Unexpectedly, we found the ASC derives from the embryonic intermedium, an ancient element of the tetrapod ankle. In some birds it comes in contact with the astragalus, and, in others, with the calcaneum. The fact that the intermedium fails to fuse early with the tibiale and develops an ossification centre is unlike any other amniotes, yet resembles basal, amphibian-grade tetrapods. The ASC originated in early dinosaurs along changes to upright posture and locomotion, revealing an intriguing combination of functional innovation and reversion in its evolution. PMID- 26563434 TI - Identification of cell types, tissues and pathways affected by risk loci in psoriasis. AB - Many common variants have been found associated with the risk of psoriasis, but the underlying mechanism is still largely unknown, mostly owing to the difficulty in dissecting the mechanism of each variant using representative cell type and tissue in biological experiments. We applied an integrative method SNPsea which has been developed by investigators in Broad, to identify the most relevant cell types, tissues, and pathways to psoriasis by assessing the condition specificity affected by psoriasis genome-wide association studies-implicated genes. We employed this software on 89 single-nucleotide polymorphisms with genome-wide significance in Han Chinese and Caucasian populations. We found significant evidence for peripheral blood CD56 + NK cells (P = 1.30 * 10(-7)), Langerhans cells (P = 4.96 * 10(-6)) and CD14+ monocytes (P < 4.80 * 10(-5)) in psoriasis. We suggested that the DNase I hypersensitivity sites in CD14+ cells were active in psoriasis (P = 2.20 * 10(-16)). In addition, we discovered that biotic stimulus response, cytokine production and NF-kappaB pathways were significantly activated in psoriasis (P < 1.00 * 10(-5)). In conclusion, we found several innate immune cells and immune pathways in psoriasis that will help guide biological experiments for psoriasis risk variants in future. PMID- 26563436 TI - Q-GDEMAR: a general method for the identification of differentially expressed genes in microarrays with unbalanced groups. AB - Microarray analysis is a powerful tool to simultaneously determine the pattern of transcription of large amounts of genes. For data post-processing distinct computational methods are currently used that, however, lead to different results regarding the genes expressed differentially. Herein, a new methodology for microarray data analysis named Q-GDEMAR is presented. It combines the quantile characterization of the entire distribution together with the Gaussian deconvolution of the central region of the microarray data distribution. Three discriminant variable variants are proposed that allow us to summarize data and compare groups even when their size is strongly unbalanced. In addition, a simple procedure to compute the false discovery rate (FDR) is also presented. The performance of the method is compared with that observed when using LIMMA (Linear Models Microarray) software as reference. In 58 out of 68 cases, Q-GDEMAR showed a higher sensitivity than LIMMA to detect differentially expressed genes (p = 1 * 10(-10)). The proposed method does not produce biased information, detecting genes with high sensitivity equally well at both tails of the distribution (p = 0.7428). Moreover, all detected genes were associated with very low levels of FDR (median value = 0.67%, interquartile range = 0.87%). Q-GDEMAR can be used as a general method for microarray analysis, but is particularly indicated when the conditions to be compared are unbalanced. The superior performance of Q-GEDEMAR is the consequence of its higher discriminative power and, the fact that it yields a univocal correspondence between the p-values and the values of the discriminating variable. Q-GDEMAR was tested only using Affymetrix microarrays. However, given that it operates after the step of data standardization, it can be used with the same quality features on any of the available mono- or dual-channel microarray platforms. PMID- 26563437 TI - Papillary thyroid cancer in a patient with congenital goitrous hypothyroidism due to a novel deletion in NIS gene. PMID- 26563439 TI - High-volume hydrodissection for abdominally based free flaps: Preliminary results. AB - INTRODUCTION: A novel method of high-volume hydrodissection that provides both subfascial and intramuscular perforator dissection of deep inferior epigastric perforators has been safely demonstrated in animals. This manuscript demonstrates our preliminary results when translating this technique to humans. METHODS: A retrospective review was performed of all free-flap breast reconstructions utilizing the high-volume hydrodissection technique performed by the senior author (DS) at the University of Florida Medical Center from January 2014 to June 2015. RESULTS: Twenty-one patients underwent 31 free-flap breast reconstructions during the study period utilizing the high-volume hydrodissection technique. No patients were lost to follow-up which averaged 8.2 months. Complications included 1 partial flap necrosis (<10%), 1 breast hematoma, 1 abdominal bulge, 2 flaps with minimal fat necrosis (<5%), and 1 abdominal wall cellulitis. CONCLUSION: High-volume hydrodissection is a safe technique to facilitate dissection of abdominally based free flaps for breast reconstruction. (c) 2015 Wiley Periodicals, Inc. Microsurgery 37:307-311, 2017. PMID- 26563438 TI - Gold nanoparticle conjugated Rad6 inhibitor induces cell death in triple negative breast cancer cells by inducing mitochondrial dysfunction and PARP-1 hyperactivation: Synthesis and characterization. AB - We recently developed a small molecule inhibitor SMI#9 for Rad6, a protein overexpressed in aggressive breast cancers and involved in DNA damage tolerance. SMI#9 induces cytotoxicity in cancerous cells but spares normal breast cells; however, its therapeutic efficacy is limited by poor solubility. Here we chemically modified SMI#9 to enable its conjugation and hydrolysis from gold nanoparticle (GNP). SMI#9-GNP and parent SMI#9 activities were compared in mesenchymal and basal triple negative breast cancer (TNBC) subtype cells. Whereas SMI#9 is cytotoxic to all TNBC cells, SMI#9-GNP is endocytosed and cytotoxic only in mesenchymal TNBC cells. SMI#9-GNP endocytosis in basal TNBCs is compromised by aggregation. However, when combined with cisplatin, SMI#9-GNP is imported and synergistically increases cisplatin sensitivity. Like SMI#9, SMI#9-GNP spares normal breast cells. The released SMI#9 is active and induces cell death via mitochondrial dysfunction and PARP-1 stabilization/hyperactivation. This work signifies the development of a nanotechnology-based Rad6-targeting therapy for TNBCs. FROM THE CLINICAL EDITOR: Protein Rad6 is overexpressed in breast cancer cells and its blockade may provide a new treatment against 3N breast cancer. The authors conjugated a small molecule inhibitor SMI#9 for Rad6 to gold nanoparticles in this study and showed that this new formulation specifically targeted chemo-resistant breast cancer cells and highlighted the importance of nanotechnology in drug carrier development. PMID- 26563440 TI - Ultrafast collisional ion heating by electrostatic shocks. AB - High-intensity lasers can be used to generate shockwaves, which have found applications in nuclear fusion, proton imaging, cancer therapies and materials science. Collisionless electrostatic shocks are one type of shockwave widely studied for applications involving ion acceleration. Here we show a novel mechanism for collisionless electrostatic shocks to heat small amounts of solid density matter to temperatures of ~keV in tens of femtoseconds. Unusually, electrons play no direct role in the heating and it is the ions that determine the heating rate. Ions are heated due to an interplay between the electric field of the shock, the local density increase during the passage of the shock and collisions between different species of ion. In simulations, these factors combine to produce rapid, localized heating of the lighter ion species. Although the heated volume is modest, this would be one of the fastest heating mechanisms discovered if demonstrated in the laboratory. PMID- 26563441 TI - Genetic analysis of the clonal stability of Chinese hamster ovary cells for recombinant protein production. AB - Chinese hamster ovary (CHO) cells are frequently used for the production of recombinant proteins for therapeutical applications. However, the recombinant protein expression level of CHO cells may reduce during long-term culture. The physiological changes related to the stability of expression were not well understood. In this study, we performed a series of genetic analysis on stable and unstable clonal derived populations. Transcriptome analysis revealed that a large number of differentially expressed genes (>100) were identified in the unstable population between early and late generations, while only a few differentially expressed genes were found in the stable population, suggesting that the gene expression change is related to the instability of recombinant protein production. On the other hand, no significant differences were found in promoter methylation or gene copy numbers in the unstable population. Taken together, our data help better understand the molecular mechanism underlying the stability of recombinant protein production in CHO cells. PMID- 26563442 TI - Biogas cleaning and upgrading with natural zeolites from tuffs. AB - CO2 adsorption on synthetic zeolites has become a consolidated approach for biogas upgrading to biomethane. As an alternative to synthetic zeolites, tuff waste from building industry was investigated in this study: indeed, this material is available at a low price and contains a high fraction of natural zeolites. A selective adsorption of CO2 and H2S towards CH4 was confirmed, allowing to obtain a high-purity biomethane (CO2 <2 g m(-3), i.e. 0.1%; H2S <1.5 mg m(-3)), suitable for injection in national grids or as vehicle fuel. The loading capacity was found to be 45 g kg(-1) and 40 mg kg(-1), for CO2 and H2S, respectively. Synthetic gas mixtures and real biogas samples were used, and no significant effects due to biogas impurities (e.g. humidity, dust, moisture, etc.) were observed. Thermal and vacuum regenerations were also optimized and confirmed to be possible, without significant variations in efficiency. Hence, natural zeolites from tuffs may successfully be used in a pressure/vacuum swing adsorption process. PMID- 26563443 TI - Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing. AB - Lymphangioleiomyomatosis (LAM) (MIM #606690) is a rare lung disorder leading to respiratory failure associated with progressive cystic destruction due to the proliferation and infiltration of abnormal smooth muscle-like cells (LAM cells). LAM can occur alone (sporadic LAM, S-LAM) or combined with tuberous sclerosis complex (TSC-LAM). TSC is caused by a germline heterozygous mutation in either TSC1 or TSC2, and TSC-LAM is thought to occur as a result of a somatic mutation (second hit) in addition to a germline mutation in TSC1 or TSC2 (first hit). S LAM is also thought to occur under the two-hit model involving a somatic mutation and/or loss of heterozygosity in TSC2. To identify TSC1 or TSC2 changes in S-LAM patients, the two genes were analyzed by deep next-generation sequencing (NGS) using genomic DNA from blood leukocytes (n = 9), LAM tissue from lung (n = 7), LAM cultured cells (n = 4), or LAM cell clusters (n = 1). We identified nine somatic mutations in six of nine S-LAM patients (67 %) with mutant allele frequencies of 1.7-46.2 %. Three of these six patients (50 %) showed two different TSC2 mutations with allele frequencies of 1.7-28.7 %. Furthermore, at least five mutations with low prevalence (<20 % of allele frequency) were confirmed by droplet digital PCR. As LAM tissues are likely to be composed of heterogeneous cell populations, mutant allele frequencies can be low. Our results confirm the consistent finding of TSC2 mutations in LAM samples, and highlight the benefit of laser capture microdissection and in-depth allele analyses for detection, such as NGS. PMID- 26563445 TI - Discussion on the paper "Real-Time Prediction of Clinical Trial Enrollment and Event Counts: A Review", by DF Heitjan, Z Ge, and GS Ying. PMID- 26563446 TI - Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study. AB - BACKGROUND: The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. METHODS: We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. DISCUSSION: By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions. PMID- 26563447 TI - An anatomical and histological study of the vascularized iliotibial tract graft. AB - BACKGROUND: An examination of the vascular anatomy of the iliotibial tract (IT) has not been previously reported. Because a flap resists infection better than an avascular graft, a vascularized IT graft is useful for reconstructive surgeries pertaining to infected wounds or wounds in contact with artificial material. The purpose of this study was to examine the vascular anatomy of the IT. MATERIALS AND METHODS: The study sample consisted of 39 limbs of freshly frozen cadavers. The study was divided into three parts. The ascending and transverse branches of the lateral circumflex femoral artery (LCFA) of all cadavers were injected with latex. Distance from the tensor fasciae latae muscle and the most distal point at which the vessel on the IT was stained by latex was recorded. A microscopic observation was performed for these limbs. The deep femoral artery (DFA) or superior lateral genicular artery (SLGA) was also observed. RESULTS: The length of the IT fed by the LCFA was 162.3 +/- 36.2 mm. The IT vascularity was located between the layered structure of the fascia and there was a vascular source for the IT within 1 mm above the IT by optical microscopy. The vascularity derived from the DFA or SLGA was not confirmed in any specimens. CONCLUSIONS: Blood supply of the IT was derived from the LCFA and a vascularized IT graft could be elevated in length to approximately 16 cm. This knowledge may be useful for improving the safety of surgery when transferring an IT flap. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:325-329, 2016. PMID- 26563448 TI - Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers. AB - Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks. PMID- 26563449 TI - Inhibition of the Androgen Receptor by Antiandrogens in Spinobulbar Muscle Atrophy. AB - Spinal-bulbar muscle atrophy (SBMA) or also named Kennedy's Disease is caused by a polyglutamine expansion (PolyQ) of the coding region of the androgen receptor (AR). The AR is a ligand-controlled transcription factor and member of the nuclear hormone receptor superfamily. The central characteristics of the SBMA pathogenicity are muscle weakness, the loss of motoneurons and the occurrence of AR-containing protein aggregates that are observed in spinal cord motoneurons and skeletal muscles induced by the AR-PolyQ expansion in the presence of androgens. The PolyQ triggers a misfolding in the AR-PolyQ and leads to protein aggregation in spinal cord motoneurons and muscle cells. The AR-PolyQ toxicity is activated by the AR ligand testosterone and dihydrotestosterone that activate the receptor and triggers nuclear toxicity by inducing AR nuclear translocation. In line with this, androgen treatment of SBMA patients worsened the SBMA symptoms. SBMA has been modeled in AR-overexpressing and AR-PolyQ-knock-in animals, but precisely how the PolyQ expansion leads to neurodegeneration is unclear. The androgen induced toxicity and androgen-dependent nuclear accumulation of AR-PolyQ protein seems to be central to the pathogenesis. Therefore, the inhibition of the androgen-activated AR-PolyQ might be a therapeutic option. Here the use of AR antagonists for treatment option of SBMA will be reviewed and discussed. PMID- 26563450 TI - TRAM1 Promotes Microglia M1 Polarization. AB - Microglia, the major immune cells of the central nervous system (CNS), can be driven to adopt M1 and M2 phenotypes. Recently, the distinct functions of M1 and M2 microglia have been intensively studied. M1-activation microglia are pro inflammatory and may contribute to the development of several CSN disorders, while M2-activation microglia are anti-inflammatory and may promote tissue reconstruction. TRAM1 is a protein involved in translocation of nascent polypeptides and functions as a sorting adaptor of TLR4. Here, we found that TRAM1 plays an important role in microglia M1 polarization. Our results showed that the expression of TRAM1 is highly induced in LPS/interferon (IFN)-gamma stimulated BV2 cells and primary microglia cells. Flag-TRAM1 transfection, but not Flag-GFP used as a control, significantly enhanced M1 polarization by strongly increasing expression of M1 makers, such as IL-6, IL-1beta, iNOS, and so on. Silence of TRAM1 effectively inhibited LPS/IFN-gamma-induced expression of M1 related genes in BV2 cells. In addition, TRAM1 was found to cooperate with TLR4 to induce an M1 genetic program in Flag-TRAM1-transfected and LPS/IFN-gamma induced BV2 cells. TRAM1 is essential for LPS/IFN-gamma induced expressions of adapter molecule (IRAK1, phosphorylation of TBK1, and IRF3) of TLR4. TRAM1 is also essential for phosphorylation of IkappaB and P65 and for P65-NF-kB translocation to nucleus. Overall, our findings showed that TRAM1 could promote microglia M1 polarization. PMID- 26563452 TI - Bacterial terpene cyclases. AB - Covering: up to 2015. This review summarises the accumulated knowledge about characterised bacterial terpene cyclases. The structures of identified products and of crystallised enzymes are included, and the obtained insights into enzyme mechanisms are discussed. After a summary of mono-, sesqui- and diterpene cyclases the special cases of the geosmin and 2-methylisoborneol synthases that are both particularly widespread in bacteria will be presented. A total number of 63 enzymes that have been characterised so far is presented, with 132 cited references. PMID- 26563451 TI - Hydrogen Peroxide-Induced Oxidative Stress Activates Proteasomal Trypsin-Like Activity in Human U373 Glioma Cells. AB - Degradation of oxidized or oxidatively modified proteins is an essential part of the cellular antioxidant defense system. 4-Hydroxy-2-nonenal, a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. The major proteolytic system for modified protein degradation is the ubiquitin proteasome pathway. However, our previous studies using U937 human leukemic cells showed that 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is degraded by cathepsin G. In the present study, U373 human glioma cells were cultured in the presence of hydrogen peroxide (H2O2) to investigate the relationships of proteasome and/or cathepsin G activities and H2O2-induced GAPDH degradation. Treatment of cells with H2O2 for 5 h in culture decreased GAPDH activity as well as its protein concentration in a concentration-dependent manner. Two proteasomal activities (peptidylglutamyl-peptide hydrolase and chymotrypsin-like hydrolase activities) and cathepsin G activity were decreased by H2O2 treatment in a concentration-dependent manner, but proteasomal trypsin like hydrolase activity increased with cell exposure to high H2O2 concentrations. Among the protease inhibitors examined here, H2O2-induced activation of trypsin like activity and GAPDH degradation were inhibited by the proteasome inhibitor lactacystin. Furthermore, H2O2-induced activation of trypsin-like activity was also inhibited by another proteasome inhibitor MG-132. These results suggested that proteasomal trypsin-like activity played an important role in eliminating oxidatively modified GAPDH formed in these cells during H2O2 exposure. PMID- 26563453 TI - Ectopic Subcutaneous Implantation of Thyroid Tissue After Gasless Transaxillary Robotic Thyroidectomy for Papillary Thyroid Cancer. PMID- 26563454 TI - A method for mapping regional oxygen and CO2 transfer in the lung. AB - This paper presents a novel approach to visualizing regional lung function, through quantitative three-dimensional maps of O2 and CO2 transfer rates. These maps describe the contribution of anatomical regions to overall gas exchange and demonstrate how transfer rates of the two gas species' differ regionally. An algorithm for generating such maps is presented, and for illustration, regional gas transfer maps were generated using values of ventilation and perfusion imaged by PET/CT for a healthy subject and an asthmatic patient after bronchoprovocation. In a sensitivity analysis, compartment values of gas transfer showed minor sensitivity to imaging noise in the ventilation and perfusion data, and moderate sensitivity to estimation errors in global lung input values, chiefly global alveolar ventilation, followed by cardiac output and arterial venous O2 content difference. Gas transfer maps offer an intuitive display of physiologically relevant lung function at a regional level, the potential for an improved understanding of pulmonary gas exchange in health and disease, and potentially a presurgical evaluation tool. PMID- 26563455 TI - Coordinated autonomic and respiratory responses evoked by alerting stimuli: Role of the midbrain colliculi. AB - Threatening stimuli trigger rapid and coordinated behavioral responses supported by cardiorespiratory changes. The midbrain colliculi can generate coordinated orienting or defensive behavioral responses, and it has been proposed that collicular neurons also generate appropriate cardiovascular and respiratory responses to support such behaviors. We have shown previously that under conditions where collicular neurons are disinhibited, coordinated cardiovascular, somatomotor and respiratory responses can be evoked independently of the cortex by auditory, visual and somatosensory stimuli. Here we report that these natural stimuli effectively increase inspiratory time most likely though phase switching. As a result the pattern of phrenic and sympathetic coupling is an inspiratory related sympathoexcitation. We propose that blockade of tonic GABAergic input in the midbrain colliculi permits alerting stimuli to drive command neurons that generate coordinated cardiovascular, respiratory and motor outputs. The outputs of these command neurons likely interact with the central respiratory pattern generator, however the precise output pathways mediating the coordinated autonomic and respiratory responses remain to be determined. PMID- 26563456 TI - Potential neuroprotective effect of lithium in bipolar patients evaluated by neuropsychological assessment: preliminary results. AB - OBJECTIVE: Accumulating evidence is delineating a neuroprotective/neurotrophic role for lithium. However, its primary effects on cognition remain ambiguous. We sought to investigate the profile of cognitive impairment in patients with bipolar disorder and to determine whether continued treatment with lithium preserves cognitive functioning. METHODS: In this cross-sectional study, we tested 15 euthymic patients with bipolar I disorder undergoing long-term clinical maintenance treatment with lithium (for at least 12 months), 15 matched patients treated with other mood-stabilizing drugs and who had never received lithium, and 15 matched healthy subjects on the Cambridge Neuropsychological Test Automated Battery. Investigated cognitive domains were visual memory, executive functions, attention, decision-making/impulsivity, and response inhibition. We controlled for age, gender, intelligence, and residual psychiatric symptomatology. RESULTS: Taken together, bipolar patients demonstrated robust deficits in visual memory and executive functions. Once subdivided in treatment subgroups, only non-lithium bipolar patients demonstrated impairments in visual memory. Attention, decision making, and response inhibition were preserved in both groups. No correlation emerged between neuropsychological tests performance, clinical, and psychological variables. CONCLUSIONS: This study is the first to our knowledge to have demonstrated, by means of a highly sensitive test of visual memory, a potential hippocampus neuroprotective effect of lithium in patients with bipolar disorder. Besides, it confirms prior findings of cognitive deficits in euthymic bipolar patients. PMID- 26563457 TI - Expression of SOCS2 mRNA and protein in the ischemic core and penumbra after transient focal cerebral ischemia in rats. AB - The suppressor of cytokine signaling 2 (SOCS2) has been reported to be involved in astroglial reactions and adult neurogenesis in the ischemic hippocampus. To elucidate whether SOCS2 is implicated in the pathophysiology of stroke, we investigate spatiotemporal regulation and identification of cell phenotypes expressing SOCS2 after transient focal cerebral ischemia. Weak hybridization signals for SOCS2 mRNA were constitutively observed in striatal neurons and upregulation of SOCS2 mRNA was induced in association with nestin-positive cells in stroke-lesioned rats. Analysis of the characteristics and phenotypes of SOCS2/nestin double-labeled cells revealed spatial differences between infarct and peri-infarct areas. SOCS2/nestin double-labeled cells in the infarct area were associated with the vasculature and were highly proliferative. In contrast, the double-labeled cells in the peri-infarct area were indeed glial fibrillary acidic protein (GFAP)-positive reactive astrocytes forming the glial scar, although nestin-negative reactive astrocytes also exhibited weak SOCS2 expression. In addition, induction of SOCS2 expression was observed in Iba1 positive cells showing a macrophage-like phenotype with amoeboid morphology; these cells were predominantly localized in the infarct area. In the peri-infarct area, only a small proportion of Iba1-positive cells with the morphology of brain macrophages expressed SOCS2 and most activated stellate microglial cells with thick and short processes exhibited weak or negligible SOCS2 expression. Thus, our results revealed the phenotypic and functional heterogeneity of SOCS2 expressing cells within infarct and peri-infarct areas, suggesting the involvement of SOCS2 in astroglial reactions and activation/recruitment of brain macrophages and its potential role in perivascular progenitors/stem cells after ischemic stroke. PMID- 26563458 TI - Analysing black phosphorus transistors using an analytic Schottky barrier MOSFET model. AB - Owing to the difficulties associated with substitutional doping of low dimensional nanomaterials, most field-effect transistors built from carbon nanotubes, two-dimensional crystals and other low-dimensional channels are Schottky barrier MOSFETs (metal-oxide-semiconductor field-effect transistors). The transmission through a Schottky barrier-MOSFET is dominated by the gate dependent transmission through the Schottky barriers at the metal-to-channel interfaces. This makes the use of conventional transistor models highly inappropriate and has lead researchers in the past frequently to extract incorrect intrinsic properties, for example, mobility, for many novel nanomaterials. Here we propose a simple modelling approach to quantitatively describe the transfer characteristics of Schottky barrier-MOSFETs from ultra-thin body materials accurately in the device off-state. In particular, after validating the model through the analysis of a set of ultra-thin silicon field effect transistor data, we have successfully applied our approach to extract Schottky barrier heights for electrons and holes in black phosphorus devices for a large range of body thicknesses. PMID- 26563460 TI - Nanosecond pulsed electric fields (nsPEFs) impact and enhanced Photofrin II((r)) delivery in photodynamic reaction in cancer and normal cells. AB - BACKGROUND: Nanosecond pulsed electric field (nsPEF) treatment is a new anti cancer strategy with ultrashort pulse duration and high intensity of electric fields. The application of nsPEFs affects all intra- and extracellular membranes and independently initiates the process of apoptosis within cancer cells, leading the tumor to slowly auto-destruct without the use of toxic drugs. METHODS: This study involves cells of gastric adenocarcinoma (EPG85-257P and EPG85-257RDB), metastatic melanoma (Me45), epidermal cancer (A431), normal keratinocytes (HaCaT), and macrophages (P388/D1). The influence of nanosecond pulses on the cellular structure and cellular proliferation was evaluated. The effect of nsPEF was determined by MTT and clonogenic assays and the efficiency was monitored by following the propidium iodide and Photofrin II((r)) uptake using FACS analysis. The cell membranes state was visualized with DHCC marker. RESULTS: nsPEFs (up to 60kV/cm) induced significant decrease of cellular viability in all cancer cells except the A431 cell line. Photodynamic reactions combined with nsPEFs induced the highest decrease of cellular viability in both gastric cell lines and skin derived cancer cells. Normal (HaCaT and P388/D1) cells were in contrary not significantly affected. Propidium iodide and Photofrin II((r)) uptake, used as markers of membrane permeabilization, were the most efficient in gastric cells. Finally, the most disturbed morphology was observed in the latter. CONCLUSIONS: This is the first attempt of combining nsPEF with photodynamic reaction using Ph II((r)) for selective destruction of cancer cells. The results indicate the potential of nsPEF for inducing cytotoxicity mainly in adenocarcinoma cells, while combined with Photofrin II((r)) and irradiation. PMID- 26563459 TI - Bethesda Categorization of Thyroid Nodule Cytology and Prediction of Thyroid Cancer Type and Prognosis. AB - BACKGROUND: Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk. METHODS: All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy. RESULTS: A total of 1291 malignancies were identified, with primary cytology AUS in 130 cases, FN in 241 cases, SUSP in 411 cases, and M in 509 cases. AUS, SUSP, and M cytology were progressively associated with an increasing risk of high-risk disease (p < 0.001), LNM (p < 0.001), ETE (p < 0.001), and margin positivity (p < 0.001). Notably, 71% of malignancies with AUS cytology were follicular variants of papillary thyroid cancer compared with 63% with SUSP cytology and only 20% with M cytology. In contrast, high-risk malignancies were diagnosed in only 4% with AUS cytology, but 9% and 27% with SUSP and M cytology, respectively. FN conveyed a significantly increased risk of follicular thyroid carcinoma compared with all other types (28% vs. 2%; p < 0.001). A composite endpoint of recurrence, distant metastases, and death similarly increased as cytology progressed from AUS to SUSP to M (p < 0.001). CONCLUSION: In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence. These data extend the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy. PMID- 26563461 TI - Microenvironment: Astrocytes silence PTEN to promote brain metastasis. PMID- 26563463 TI - Genome instability: Stress management by the FA pathway. PMID- 26563464 TI - Metastasis: Directions to metastatic sites. PMID- 26563462 TI - Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. AB - During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC. PMID- 26563465 TI - Diagnosis: RNA-seq for blood-based pan-cancer diagnostics. PMID- 26563466 TI - Optimization of a New Mass Spectrometry Method for Measurement of Breast Milk Iodine Concentrations and an Assessment of the Effect of Analytic Method and Timing of Within-Feed Sample Collection on Breast Milk Iodine Concentrations. AB - BACKGROUND: Breast milk iodine concentration (BMIC) may be an indicator of iodine status during lactation, but there are few data comparing different analytical methods or timing of sampling. The aims of this study were: (i) to optimize a new inductively coupled plasma mass spectrometry (ICP-MS) method; and (ii) to evaluate the effect of analytical method and timing of within-feed sample collection on BMIC. METHODS: The colorimetric Sandell-Kolthoff method was evaluated with (a) or without (b) alkaline ashing, and ICP-MS was evaluated using a new (129)I isotope ratio approach including Tellurium (Te) for mass bias correction (c) or external standard curve (d). From iodine-sufficient lactating women (n = 97), three samples were collected within one breast-feeding session (fore-, mid-, and hind-feed samples) and BMIC was analyzed using (c) and (d). RESULTS: Iodine recovery from NIST SRM1549a whole milk powder for methods (a)-(d) was 67%, 24%, 105%, and 102%, respectively. Intra- and inter-assay coefficients of variation for ICP-MS comparing (c) and (d) were 1.3% versus 5.6% (p = 0.04) and 1.1% versus 2.4% (p = 0.33). The limit of detection (LOD) was lower for (c) (0.26 MUg/kg) than it was for (d) (2.54 MUg/kg; p = 0.02). Using (c), the median [95% confidence interval (CI) obtained by bootstrap] BMIC (MUg/kg) in foremilk (179 [CI 161-206]) and in mid-feed milk (184 [CI 160-220]) were not significantly different (p = 0.017), but were higher than in hindmilk (175 [CI 153-216]; p < 0.001). In foremilk using (d), BMIC was 199 ([CI 182-257]; p < 0.001 vs. (c)). The variation in BMIC comparing (c) and (d) (13%) was greater than variation within feeding (5%; p < 0.001). CONCLUSIONS: Because of poor recoveries, (a) and (b) should not be used to measure BMIC. Compared with (d), (c) has the advantages of higher precision and a lower LOD. In iodine-sufficient women, BMIC shows low variation within a breast-feeding session, so timing of sampling is not a major determinant of BMIC. PMID- 26563467 TI - Marine Metagenome as A Resource for Novel Enzymes. AB - More than 99% of identified prokaryotes, including many from the marine environment, cannot be cultured in the laboratory. This lack of capability restricts our knowledge of microbial genetics and community ecology. Metagenomics, the culture-independent cloning of environmental DNAs that are isolated directly from an environmental sample, has already provided a wealth of information about the uncultured microbial world. It has also facilitated the discovery of novel biocatalysts by allowing researchers to probe directly into a huge diversity of enzymes within natural microbial communities. Recent advances in these studies have led to a great interest in recruiting microbial enzymes for the development of environmentally-friendly industry. Although the metagenomics approach has many limitations, it is expected to provide not only scientific insights but also economic benefits, especially in industry. This review highlights the importance of metagenomics in mining microbial lipases, as an example, by using high-throughput techniques. In addition, we discuss challenges in the metagenomics as an important part of bioinformatics analysis in big data. PMID- 26563468 TI - CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy. AB - A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements. PMID- 26563469 TI - Plant functional traits suggest a change in novel ecological strategies for dominant species in the stages of forest succession. AB - In forest succession, the ecological strategies of the dominant species that are based on functional traits are important in the determination of both the mechanisms and the potential directions of succession. Thirty-one plots were established in the Loess Plateau region of northern Shaanxi in China. Fifteen leaf traits were measured for the 31 dominant species that represented the six stages of succession, and the traits included four that were related to morphology, seven to stoichiometry and four to physiological ecology. The species from the different successional stages had different patterns of distribution of the traits, and different key traits predicted the turnover of the species during succession. The ash and the cellulose contents were key regulatory factors of species turnover in the early successional communities, and the trait niche forces in sugar and leaf dry mass content might become more important with the progression of succession. When only the three herb stages were considered, a progressive replacement of the ruderal by the competitive-ruderal species occurred in the intermediate stages of succession, which was followed by the stress-tolerant-competitive or the competitive-stress tolerant-ruderal strategists late in the succession. Thus, the different species that occurred in the different stages of succession shared different trait-based ecological strategies. Additionally, these differences occurred concomitantly with a shift toward competitive-stress tolerant-ruderal strategies. PMID- 26563470 TI - Cyclodextrin-Functionalized Monolithic Capillary Columns: Preparation and Chiral Applications. AB - In this review, the recently reported approaches for the preparation of cyclodextrin-functionalized capillary monolithic columns are highlighted, with few applications in chiral separations using capillary liquid chromatography (CLC) and capillary electrochromatography (CEC). Chirality 28:97-109, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26563471 TI - Inhibition of Pten deficient Castration Resistant Prostate Cancer by Targeting of the SET - PP2A Signaling axis. AB - The PP2A signaling axis regulates multiple oncogenic drivers of castration resistant prostate cancer (CRPC). We show that targeting the endogenous PP2A regulator, SET (I2PP2A), is a viable strategy to inhibit prostate cancers that are resistant to androgen deprivation therapy. Our data is corroborated by analysis of prostate cancer patient cohorts showing significant elevation of SET transcripts. Tissue microarray analysis reveals that elevated SET expression correlates with clinical cancer grading, duration of neoadjuvant hormone therapy (NHT) and time to biochemical recurrence. Using prostate regeneration assays, we show that in vivo SET overexpression is sufficient to induce hyperplasia and prostatic intraepithelial neoplasia. Knockdown of SET induced significant reductions in tumorgenesis both in murine and human xenograft models. To further validate SET as a therapeutic target, we conducted in vitro and in vivo treatments using OP449 - a recently characterized PP2A-activating drug (PAD). OP449 elicits robust anti-cancer effects inhibiting growth in a panel of enzalutamide resistant prostate cancer cell lines. Using the Pten conditional deletion mouse model of prostate cancer, OP449 potently inhibited PI3K-Akt signaling and impeded CRPC progression. Collectively, our data supports a critical role for the SET-PP2A signaling axis in CRPC progression and hormone resistant disease. PMID- 26563472 TI - In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds. AB - In this study, polycaprolactone (PCL)-based composite scaffolds containing 50wt% of 45S5 Bioglass((r)) (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using an additive manufacturing technique for bone tissue engineering purposes. The PCL scaffolds were surface coated with calcium phosphate (CaP) to enable further comparison of the osteoinductive potential of different scaffolds: PCL (control), PCL/CaP-coated, PCL/50-45S5 and PCL/50-SrBG scaffolds. The PCL/50-45S5 and PCL/50-SrBG composite scaffolds were reproducibly manufactured with a morphology highly resembling that of PCL only scaffolds. However, 50wt% loading of the bioactive glass (BG) particles into the PCL bulk decreased the scaffold's compressive Young's modulus. Coating of PCL scaffolds with CaP had a negligible effect on the scaffold's porosity and compressive Young's modulus. When immersed in culture media, BG dissolution ions (Si and Sr) were detected for up to 10weeks in the immersion media and surface precipitates were formed on both PCL/50-45S5 and PCL/50-SrBG scaffolds' surfaces, indicating good in vitro bioactivity. In vitro cell studies were conducted using sheep bone marrow stromal cells (BMSCs) under non-osteogenic or osteogenic conditioned media, and under static or dynamic culture environments. All scaffolds were able to support cell adhesion, growth and proliferation. However, when cultured in non-osteogenic media, only PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds showed an up-regulation of osteogenic gene expression. Additionally, under a dynamic culture environment, the rate of cell growth, proliferation and osteoblast-related gene expression was enhanced across all scaffold groups. Subsequently, PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds, with or without seeded cells, were implanted subcutaneously into nude rats for the evaluation of osteoinductivity potential. After 8 and 16weeks, host tissue infiltrated well into the scaffolds, but no mature bone formation was observed in any scaffolds groups. STATEMENT OF SIGNIFICANCE: This novelty of this research work is that it provide a comprehensive comparison, both in vitro and in vivo, between 3 different composite materials widely used in the field of bone tissue engineering for their bone regeneration capabilities. The materials used in this study include polycaprolactone, 45S5 Bioglass, strontium-substituted bioactive glass and calcium phosphate. Additionally, the composite materials were fabricated into the form of 3D scaffolds using additive manufacturing technique, a widely used technique in tissue engineering. PMID- 26563473 TI - Features Predictive of Distant Metastasis in Papillary Thyroid Microcarcinomas. AB - BACKGROUND: The recent increase in the incidence of thyroid cancer has been mainly attributed to papillary thyroid microcarcinomas (PTMCs), and many studies have suggested conservative strategies for the diagnosis and treatment of PTMC. However, PTMCs may be associated with distant metastasis. This study aimed to evaluate the clinicopathological features and identify the risk factors for distant metastasis in patients with PTMCs. METHODS: The medical records of 8808 patients who were diagnosed with PTMC from 1999 to 2012 were reviewed, and 12 (0.1%) patients with distant metastasis were identified. Forty-one PTMC patients who initially had lateral cervical lymph node (LN) metastasis and were cured with no evidence of a distant metastasis were also selected as a control group. RESULTS: Of the 12 patients with distant metastasis, nine had synchronous metastasis and three had metachronous metastasis. All 12 patients had primary tumors >0.5 cm and cervical LN metastasis at initial surgery. Ten patients had clinically apparent lateral cervical LN metastases, while two patients had only microscopic involvement of a central LN. Four patients died of thyroid carcinoma. Disease-specific mortality was associated with old age, large metastatic LNs with extranodal extension, and aggressive pathologic subtype of metastatic LNs. When the clinicopathological features of the patients with distant metastasis were compared with the control patients, the presence of extranodal extension and change to an aggressive pathologic subtype of metastatic LNs were significantly associated with distant metastasis and persistent structural distant PTMC metastasis. CONCLUSIONS: Most patients with PTMC demonstrate excellent clinical outcomes, and distant metastases rarely occur. However, distant metastasis of PTMC can be fatal. Performing a meticulous pathologic examination of metastatic LNs to identify the presence of extranodal extension and the pathologic subtype of metastatic LNs helps to assess the risk of a distant metastasis in patients with PTMC. PMID- 26563474 TI - Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects. AB - BACKGROUND AIMS: Fractures with a critical size bone defect (e.g., open fracture with segmental bone loss) are associated with high rates of delayed union and non union. The prevention and treatment of these complications remain a serious issue in trauma and orthopaedic surgery. Autologous cancellous bone grafting is a well established and widely used technique. However, it has drawbacks related to availability, increased morbidity and insufficient efficacy. Mesenchymal stromal cells can potentially be used to improve fracture healing. In particular, human fat tissue has been identified as a good source of multilineage adipose-derived stem cells, which can be differentiated into osteoblasts. The main issue is that mesenchymal stromal cells are a heterogeneous population of progenitors and lineage-committed cells harboring a broad range of regenerative properties. This heterogeneity is also mirrored in the differentiation potential of these cells. In the present study, we sought to test the possibility to enrich defined subpopulations of stem/progenitor cells for direct therapeutic application without requiring an in vitro expansion. METHODS: We enriched a CD146+NG2+CD45- population of pericytes from freshly isolated stromal vascular fraction from mouse fat tissue and tested their osteogenic differentiation capacity in vitro and in vivo in a mouse model for critical size bone injury. RESULTS: Our results confirm the ability of enriched CD146+NG2+CD45- cells to efficiently generate osteoblasts in vitro, to colonize cancellous bone scaffolds and to successfully contribute to regeneration of large bone defects in vivo. CONCLUSIONS: This study represents proof of principle for the direct use of enriched populations of cells with stem/progenitor identity for therapeutic applications. PMID- 26563475 TI - Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis. AB - Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPalpha were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma. PMID- 26563476 TI - A Computer-Aided Diagnosis Scheme For Detection Of Fatty Liver In Vivo Based On Ultrasound Kurtosis Imaging. AB - Fatty liver disease is a common disease caused by alcoholism, obesity, and diabetes, resulting in triglyceride accumulation in hepatocytes. Kurtosis coefficient, a measure of the peakedness of the probability distribution, has been applied to the analysis of backscattered statistics for characterizing fatty liver. This study proposed ultrasound kurtosis imaging as a computer-aided diagnosis (CAD) method to visually and quantitatively stage the fatty liver. A total of 107 patients were recruited to participate in the experiments. The livers were scanned using a clinical ultrasound scanner with a 3.5-MHz curved transducer to acquire the raw ultrasound backscattered signals for kurtosis imaging. The kurtosis image was constructed using the sliding window technique. Experimental results showed that kurtosis imaging has the ability to visualize and quantify the variation of backscattered statistics caused by fatty infiltration. The kurtosis coefficient corresponding to liver parenchyma decreased from 5.41 +/- 0.89 to 3.68 +/- 0.12 with increasing the score of fatty liver from 0 (normal) to 3 (severe), indicating that fatty liver reduces the degree of peakedness of backscattered statistics. The best performance of kurtosis imaging was found when discriminating between normal and fatty livers with scores >=1: the area under the curve (AUC) is 0.92 at a cutoff value of 4.36 (diagnostic accuracy =86.9 %, sensitivity =86.7 %, specificity =87.0 %). The current findings suggest that kurtosis imaging may be useful in designing CAD tools to assist in physicians in early detection of fatty liver. PMID- 26563477 TI - alpha-Synuclein pathology in the cranial and spinal nerves in Lewy body disease. AB - Accumulation of phosphorylated alpha-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated alpha-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that alpha-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA. PMID- 26563478 TI - Complications of ESIN osteosynthesis--Experience in 270 patients. AB - BACKGROUND: Elastic stable intramedullary nailing (ESIN) osteosynthesis has been used in our department for the treatment of long-bone fractures in children and adolescents for more than 17 years. During this period we have shown that ESIN has several advantages compared with other methods of treatment. However, as with every other method, ESIN has its drawbacks and complications. These occur primarily if indication criteria are not respected or ESIN technique is inadequate. This paper presents the rate of complications that occurred with this method in our patients, and the means of prevention and treatment of these complications. PATIENTS AND METHODS: A total of 270 patients treated with ESIN osteosynthesis for fractures of long bones of the extremities completed treatment. The study was conducted at the Department of Child Surgery and Orthopaedics of the Clinical Hospital Centre in Rijeka. All the Nancy Nails used in the study were of the same quality, from one manufacturer and were applied using the standard ESIN technique. In 228 patients (84%), ESIN was the primary treatment, whereas in the remaining 42 patients (16%), ESIN was applied after an attempt at manual reposition and immobilisation of bone fragments. All patients had control radiography at least three times and postoperative monitoring was conducted for at least two years. RESULTS: A total of 35 of the 270 observed patients developed complications; some patients had several complications. There were 53 early intraoperational complications and 29 late postoperative complications. All complications resolved with appropriate therapy. The treatment was satisfactory in all patients except those with an elongation of the extremity (leg) of more than 1cm. CONCLUSION: Postoperative complications related to the ESIN method of osteosynthesis in the patients in this study were detected by radiological control examinations and long-term clinical monitoring. All the complications of ESIN were relatively easy to treat with current medical methods. The frequency of particular complications is significantly reduced if indication criteria for ESIN are respected and correct ESIN technique is used. PMID- 26563479 TI - Definition of polytrauma: Discussion on the objective definition based on quantitative estimation of multiply injured patients during wartime. AB - AIM: There is a clear lack of consensus on a validated definition of the term "polytrauma". This study presents and classifies the extent of injuries during wartime in Croatia using the Revised Trauma Score and Injury Severity Score (TRISS) and compares the scores with a clinical estimation based on subjective assessments of polytraumatised and non-polytraumatised patients. METHODS: We analysed the data from 426 war victims who sustained multiple injuries and were managed at Osijek University Hospital from September 1st 1991 to December 31st 1991. The victims were divided into polytraumatised (n=149) and multitraumatised (n=277) patients according to the initial clinical estimation of the extent of injury. Patients classified as monotraumatised were excluded from this study. The assessment was based on the following definition of polytrauma: simultaneous injury of two or more body regions or anatomical systems with at least one injury being life-threatening. All data were scored retrospectively using TRISS methodology. RESULTS: Two patients classified as polytraumatised had an ISS of less than 16, and one patient classified as multitraumatised had an ISS of more than 16. The difference between the actual (29.5%) and expected (40.44%) postoperative mortality in the polytraumatised group was statistically significant (p=0.0016), whereas in the multitraumatised group, the difference between the actual (3.2%) and expected (3.04%) postoperative mortality was not significant (p=0.6103). CONCLUSIONS: The data show that clinical and subjective assessment of polytraumatised patients can be useful in the management of such cases and can be tested retrospectively using TRISS methodology. PMID- 26563480 TI - Treatment of proximal fifth metatarsal bone fractures in athletes. AB - Proximal fifth metatarsal (V MT) bone fractures are common injuries that are a major diagnostic and therapeutic challenge. Lawrence and Botte considered different treatment options and the possibility of recovery and divided these fractures into three different regions: tuberosity avulsion fractures (zone I), acute fractures of the metaphysis at the level of the intermetatarsal junction (zone II) and proximal diaphysis stress fracture (zone III). A total of 42 athletes with fracture of the V MT bone in zone II and III were treated in our institution during a 6-year period. All patients were offered surgical treatment, but nine patients refused surgery. Thus, the patients were divided into two groups: group 1 comprised 33 patients who underwent an intramedullary screw fixation operation under regional anaesthesia immediately after the fracture was diagnosed; group 2 contained the remaining nine patients who had refused surgery and received conservative therapy with non-weight-bearing short-leg casts or orthosis. Follow-up ranged from 6 to 24 months. All fractures healed in group 1: healing occurred within 8 weeks in 26 patients and was prolonged to 16 to 18 weeks in four patients. In group 2, fractures healed in four patients but did not heal in five patients even after 6 months. Four of the five patients in whom the fracture did not heal required subsequent osteosynthesis because they had constant problems that caused absence from sport. After the operation, their fractures healed in an average of 10 weeks. One patient decided not to undergo the operation due to the absence of subjective symptoms. Three patients in group 1 who started intensive training sustained a refracture and underwent re operation in which osteosynthesis was performed with a stronger screw. The fractures then healed again. Treatment results were evaluated radiologically and clinically using the Modified Foot Score. Results in group 1 were significantly better than those in group 2 and there was an earlier return to full athletic activity. The authors concluded that intramedullary fixation of V MT zone II and III fractures with cannulated compression screws was associated with excellent functional results and early and complete recovery. PMID- 26563481 TI - Prognostic significance of specific injury patterns in casualties of traffic related accidents. AB - AIM: Fatal triad and ipsilateral dyad are patterns of pedestrian injuries related to significant mortality in traffic-related accidents. The aim of this research was to investigate the correlation between specific injury patterns and fatal outcome in other participants of traffic-related accidents. METHODS: This was a retrospective study of traffic-related accidents in the broader area of the city of Osijek in a five-year period from 1995 to 1999. Autopsy results from the Institute of Pathology and Forensic Medicine of the Clinical Hospital Centre Osijek were analysed of individuals who died after their accident. The total severity of injuries was measured using the ISS. Logistic regression analysis was used for assessing the correlation between specific injury patterns and an early outcome from the severe injury. RESULTS: There were 213 individuals included in the study: 72 pedestrians and 141 other participants (drivers, assistant drivers, passengers, cyclists and motorcyclists). A total of129 individuals died on the spot and 84 died in the hospital during the first 48h. Femoral and pelvic fracture, fatal triad and both variants of ipsilateral dyad were related to higher ISS values. Ipsilateral fracture of upper and lower extremities (ipsilateral dyad 1) was associated with a 4.59 times higher risk of an immediate fatal outcome in the total sample. In pedestrians, the risk was 5.99 higher, and in other participants, the risk was 4.11 times higher. CONCLUSION: Specific skeletal injuries and injury patterns are a significant indicator for total injury severity and related poor prognosis for all participants of traffic related injuries, not only for pedestrians. In this study, the ipsilateral fracture of upper and lower extremity was related to the largest total severity of injuries and the poorest prognosis. PMID- 26563482 TI - Indication for resuscitative thoracotomy in thoracic injuries-Adherence to the ATLS guidelines. A forensic autopsy based evaluation. AB - BACKGROUND: The appropriate indications for Resuscitative Thoracotomy (RT) are still debated in the literature and various guidelines have been proposed. This study aimed to evaluate whether Advanced Trauma Life Support (ATLS) guidelines for RT were applied correctly and to evaluate the proportion of deceased patients with potentially reversible thoracic lesions (PRTL). METHODS: The database at the Department of Forensic Medicine at Copenhagen University was queried for autopsy cases with thoracic lesions indicated by the SNOMED autopsy coding system. Patients were included if thoracic lesions were caused by a traumatic event with trauma team activation. Patient cases were blinded for any surgical intervention and evaluated independently by two reviewers for indications or contraindications for RT as determined by the ATLS guidelines. Second, autopsy reports were evaluated for the presence of PRTL. RESULTS: Sixty-seven patients met the inclusion criteria. Two were excluded due to insufficient data. The overall agreement with guidelines was 86% and 77% for blunt and penetrating trauma, respectively. For patients submitted to RT the overall agreement with guidelines was 63% being 45% and 74% for blunt and penetrating trauma, respectively. For patients who did not undergo RT the agreement with guidelines was 100%. In all cases where RT was performed in agreement between guidelines and the clinical decision the autopsy reports showed PRTL in 16 (84%) patients. In cases of non agreement PRTL were found in 9 (82%) patients. CONCLUSIONS: Agreement with ATLS guidelines for RT was 63% for intervention and 100% for non-intervention in deceased patients with thoracic trauma. Agreement was higher for penetrating trauma than for blunt trauma. The adherence to guidelines did not improve the ability to predict autopsy findings of PRTL. Although the study has methodical limitations it represents a novel approach to the evaluation of the clinical use of RT guidelines. PMID- 26563483 TI - Splenic rupture in infectious mononucleosis: A systematic review of published case reports. AB - INTRODUCTION: Infectious mononucleosis (IM) is a common viral illness that predominantly causes sore throat, fever and cervical lymphadenopathy in adolescents and young adults. Although usually a benign, self-limiting disease, it is associated with a small risk of splenic rupture, which can be life threatening. It is common practice therefore to advise avoiding vigorous physical activity for at least 4-6 weeks, however this is not based on controlled trials or national guidelines. We reviewed published case reports of splenic rupture occurring in the context of IM in an attempt to ascertain common factors that may predict who is at risk. METHOD: A search of MEDLINE and EMBASE databases was performed for case reports or series published between 1984 and 2014. In total, 52 articles or abstracts reported 85 cases. Data was extracted and compiled into a Microsoft Excel((r)) spreadsheet. RESULTS: The average patient age was 22 years, the majority (70%) being male. The average time between onset of IM symptoms and splenic rupture was 14 days, with a range up to 8 weeks. There was a preceding history of trauma reported in only 14%. Abdominal pain was the commonest presenting complaint of splenic rupture, being present in 88%. 32% were successfully managed non-operatively, whereas 67% underwent splenectomy. Overall mortality was 9%. CONCLUSIONS AND RECOMMENDATIONS: From our data, it appears that men under 30 within 4 weeks of symptom onset are at highest risk of splenic rupture, therefore particular vigilance in this group is required. As cases have occurred up to 8 weeks after the onset of illness, we would recommend avoidance of sports, heavy lifting and vigorous activity for 8 weeks. Should the patient wish to return to high risk activities prior to this, an USS should be performed to ensure resolution of splenomegaly. The majority of cases reviewed had no preceding trauma, although previous studies have suggested this may be so minor as to go unnoticed by the patient. It is therefore prudent to warn patients about the symptoms of splenic rupture to ensure prompt presentation and minimise treatment delay rather than focusing purely on activity limitation. PMID- 26563485 TI - Investigation on novel raceway pond with inclined paddle wheels through simulation and microalgae culture experiments. AB - The open raceway ponds are nowadays the most used large-scale reactors for microalgae culture. To avoid the stacking of microalgae, the paddle wheels are the most widely used to circulate and mix the culture medium. In this paper, a numerical simulation using computational fluid dynamics (CFD) was used to investigate the hydrodynamic characteristics of open raceway ponds with different types of paddle wheels (the traditional paddle wheels and the novel paddle wheels with specially inclined angle of the blades). The particle image velocimetry (PIV) was used to validate the reliability of the CFD model. The CFD simulation results showed that the novel raceway pond with 15 degrees inclined angle of the blades had the best mixing efficiency under the same power consumption. Lastly, the results of microalgae culture experiments showed that the growth rates of Chlorella pyrenoidosa in the novel raceway pond with 15 degrees inclined angle of the blades were higher than those in the traditional reactor. The results of the culture experiments and CFD simulations were identical with each other. Therefore, a novel paddle wheel with 15 degrees inclined angle of the blades was obtained for better microalgae cultivation. PMID- 26563484 TI - Myc and Omomyc functionally associate with the Protein Arginine Methyltransferase 5 (PRMT5) in glioblastoma cells. AB - The c-Myc protein is dysregulated in many human cancers and its function has not been fully elucitated yet. The c-Myc inhibitor Omomyc displays potent anticancer properties in animal models. It perturbs the c-Myc protein network, impairs c-Myc binding to the E-boxes, retaining transrepressive properties and inducing histone deacetylation. Here we have employed Omomyc to further analyse c-Myc activity at the epigenetic level. We show that both Myc and Omomyc stimulate histone H4 symmetric dimethylation of arginine (R) 3 (H4R3me2s), in human glioblastoma and HEK293T cells. Consistently, both associated with protein Arginine Methyltransferase 5 (PRMT5)--the catalyst of the reaction--and its co-factor Methylosome Protein 50 (MEP50). Confocal experiments showed that Omomyc co localized with c-Myc, PRMT5 and H4R3me2s-enriched chromatin domains. Finally, interfering with PRMT5 activity impaired target gene activation by Myc whereas it restrained Omomyc-dependent repression. The identification of a histone-modifying complex associated with Omomyc represents the first demonstration of an active role of this miniprotein in modifying chromatin structure and adds new information regarding its action on c-Myc targets. More importantly, the observation that c-Myc may recruit PRMT5-MEP50, inducing H4R3 symmetric di methylation, suggests previously unpredictable roles for c-Myc in gene expression regulation and new potential targets for therapy. PMID- 26563486 TI - Hip fractures in patients older than 75 years old: Retrospective analysis for prognostic factors. AB - BACKGROUND: Proximal femoral fractures are often seen in older patients and are associated with high mortality. Introduction to old age population is latening due to advancements in medical sciences and increasing life expectancy. OBJECTIVES: The aim of the study was to evaluate factors affecting mortality in patients above 75 years of age who had been operated because of proximal femur fractures. PATIENTS AND METHODS: Patients with age 75 and over who suffers from post-fall proximal femoral fracture who underwent surgery with one of following three methods (hemiarthroplasty, proximal femoral nail or total hip arthroplasty) were evaluated retrospectively. Effects on mortality were examined for factors such as type of surgery, type of anesthesia, preoperative ASA score (American Society of Anesthesiologists Score), need for intensive care, need for blood transfusion, operation waiting time and hospitalization duration. 115 patients who met inclusion criterion were included in the study out of 224 overall. 75 patients were women and 40 were males. RESULTS: Mortality rate after first year was found to be 40%. Patients over 85 years old had higher rates of mortality (p = 0,0003) than respectively younger patients (75-85). Sex was found to have no impact on mortality (p = 0.5039). There was no statistically significant difference in terms ASA score (p = 0.1518). Order of applied surgical methods with mortality risk rates was found to be total hip arthroplasty > hemiarthroplasty > proximal femoral nail (p = 0.0003). Type of anesthesia, the use of cement during arthroplasty, operation waiting time and hospitalization duration was not directly related with mortality rate (type of anesthesia p = 0.63, the use of cement during arthroplasty p = 0.223, operation waiting time p = 0.5 and hospitalization duration p = 0.19). CONCLUSIONS: Age is the primary risk factor on first year mortality in patients older than 75 years old with hip fractures. Addition to older age, more need to blood transfusions, and arthroplasty are other risk factors for first year mortality. It should be kept in mind that after 75 years old first year mortality may be higher if the patient is treated with arthroplasty. PMID- 26563487 TI - Influence of colectomy type and resected specimen length on number of harvested lymph nodes. AB - BACKGROUND: The optimal (minimal) number of harvested nodes is still a matter of debate. We prospectivly evaluated the relation between specimen length and tumor location to the number of harvested nodes and rate of node positivity. METHODS: Specimens of right hemicolectomy, left hemicolectomy, and subtotal colectomy were assessed for specimen length, overall number of harvested lymph nodes, and lymph node ratio. RESULTS: Left hemicolectomies were performed in 106 patients, right hemicolectomies in 90, and subtotal colectomies in 9. The mean number of retrieved lymph nodes was significantly higher in patients with right and subtotal colectomies compared to left colectomies: 33, 44, and 24, respectively. Positive nodes were found in 34% of the patients with right hemicolectomies, 55% in the subtotal group, and 35% in the left hemicolectomy group (not statistically significant). The length of the resected specimen was significantly longer in patients with right and subtotal colectomies compared to left colectomy: 31, 83, and 19 cm, respectively, but the ratio of lymph nodes to the length of the specimen was not statistically different: 1.19, 0.58, and 1.55, respectively. CONCLUSIONS: It appears that the additional length of resection in right colectomies compared to left colectomies leads to an increase in the average number of resected nodes, a change that did not translate into an increase in the number of positive nodes, nor in the ratio of patients with positive nodes. PMID- 26563488 TI - Extracorporeal life support in polytraumatized patients. AB - Major trauma is a leading cause of death, particularly amongst young patients. Conventional therapies for post-traumatic cardiovascular shock and acute pulmonary failure may sometimes be insufficient and even dangerous. New approaches to trauma care and novel salvage techniques are necessary to improve outcomes. Extracorporeal life support (ECLS) has proven to be effective in acute cardiopulmonary failure from different etiologies, particularly when conventional therapies fail. Since 2008 we have used ECLS as a rescue therapy in severe poly trauma patients with refractory clinical setting (cardiogenic shock, cardiac arrest, and/or pulmonary failure). The rationale for using ECLS in trauma patients is to support cardiopulmonary function, providing adequate systemic perfusion and, therefore, avoiding consequent multi-organ failure and permitting organ recovery. From our data ECLS, utilizing heparin-coated support to avoid systemic anticoagulation, is a valuable option to support severely injured patients when conventional therapies are insufficient. It is safe, feasible, and effective in providing hemodynamic support and blood-gas exchange. Moreover, we have identified several pre-ECLS patient characteristics useful in predicting ECLS treatment appropriateness in severe poly-traumatized patients. These might be helpful in deciding whether the ECLS should be initiated in patients who are severely complex and compromised. Future improvements in materials and techniques are expected to make ECLS even easier and safer to manage, leading to a further extension of its use in severely injured patients. PMID- 26563489 TI - Bile acid elevation after Roux-en-Y gastric bypass is associated with cardio protective effect in Zucker Diabetic Fatty rats. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) may improve cardiometabolic risk through alteration of bile acids and L-PGDS levels. OBJECTIVE: The objective of this study was to investigate the effect of RYGB on aortic wall thickness, in relation to bile acid and L-PGDS metabolism. METHODS: Zucker diabetic fatty (ZDF) rats were divided into two groups, ad lib (n = 4), and RYGB (n = 6). Bile acid and L-PGDS were measured presurgery and fourteen weeks post-surgery. RESULTS: Elevation of bile acid levels following RYGB in Zucker Diabetic Fatty (ZDF) rodents was observed, as compared to ad lib. RYGB in ZDF rodents led to a significantly decreased aortic wall thickness (25%) as compared to ad lib control. Although bile acid metabolism is implicated in these alterations, other mediators are likely involved. Our laboratory has demonstrated lipocalin prostaglandin D2 synthase (L-PGDS) is a kno n cardiometabolic modulator that also functions as a bile acid binding protein. Therefore, L-PGDS levels were measured and a significant elevation was observed with RYGB compared to ad lib control. CONCLUSION: Based on these findings, RYGB showed beneficial effect on aortic wall thickness, possibly through bile acids and L-PGDS elevation in a severely obese and diabetic rodent model. PMID- 26563490 TI - Predicting individual change during the course of treatment. AB - OBJECTIVE: An empirically derived prediction model was developed in a private practice setting to monitor on-track and off-track weekly treatment progress in an intensive outpatient program (IOP). METHOD: The predictive equation was derived as a function of the baseline measure and time. The formulae for the predictive equations were derived from two groups of psychiatric patients (N = 400 each) in an IOP diagnosed with major depression. Each equation was cross validated between these two psychiatric IOP samples and a dual diagnosis sample (N = 198) using kappa, the reliable change index (RCI), receiver operating characteristic curves, and Youden's J. RESULTS: Using varying RCI classifications, approximately 66-75% of both samples reliably improved, 23-24% were indeterminant, and only 1-3% deteriorated. Of patients identified as off track, which included patients classified as indeterminant and deteriorated, 83% were correctly identified. Of those identified as on-track, 85% were correctly classified. Those identified as on-track (85%) are highly likely to respond to treatment as expected. CONCLUSIONS: The overall efficiency index (hit rate) for the correct classification of all patients was 85%. Implications for using this predictive model as a clinical support decision tool with relatively homogeneous populations in other practice settings are discussed. PMID- 26563491 TI - The effect of textured ballet shoe insoles on ankle proprioception in dancers. AB - BACKGROUND: Impaired ankle inversion movement discrimination (AIMD) can lead to ankle sprain injuries. The aim of this study was to explore whether wearing textured insoles improved AIMD compared with barefoot, ballet shoes and smooth insoles, among dancers. METHODS: Forty-four adolescent male and female dancers, aged 13-19, from The Australian Ballet School were tested for AIMD while barefoot, wearing ballet shoes, smooth insoles, and textured insoles. RESULTS: No interaction was found between the four different footwear conditions, the two genders, or the two levels of dancers in AIMD (p > .05). An interaction was found between the four different footwear conditions and the three tertiles when tested in ballet shoes (p = .006). Although significant differences were found between the upper tertiles and the lower tertiles when tested with ballet shoes, barefoot and with smooth insoles (p < .001; p < .001; p = .047, respectively), when testing with textured insoles dancers in the lower tertile obtained similar scores to those obtained by dancers in the upper tertile (p = .911). CONCLUSION: Textured insoles improved the discrimination scores of dancers with low AIMD, suggesting that textured insoles may trigger the cutaneous receptors in the plantar surface, increasing the awareness of ankle positioning, which in turn might decrease the chance of ankle injury. PMID- 26563492 TI - Salvage autologous fascial sling after failed synthetic midurethral sling: Greater than 3-year outcomes. AB - OBJECTIVE: To determine long-term surgical outcomes of salvage autologous fascial sling placement after a failed synthetic midurethral sling. METHODS: Women who had undergone autologous fascial sling placement without concomitant pelvic surgery for a failed synthetic midurethral sling utilizing mesh with a minimum follow up of 36 months were identified. Charts were reviewed, and patients were contacted by telephone. Success was determined by the Patient Global Impression of Improvement. Secondary measures included the Incontinence Severity Index questionnaire, patient recommendation of the autologous fascial sling and need for further incontinence surgery. RESULTS: A total of 35 patients met the criteria, and 21 were successfully contacted. Of those contacted, the median age at surgery was 67 years (range 53-81 years) and at the time of the survey was 75 years (range 63-84 years) with median follow up of 74 months (range 36-127 years). Preoperatively, 12 patients (57.1%) had urethral hypermobility and 13 patients (61.9%) had mixed urinary incontinence. Eight patients (38.1%) had concomitant sling excision with five of those combined with urethrolysis at the time of the salvage operation. Patient Global Impression of Improvement success was noted in 16 patients (76.2%). A total of 11 patients (52.4%) were dry or had slight incontinence by the Incontinence Severity Index. One patient required additional anti-incontinence surgery (4.8%). A total of 18 patients (85.7%) recommended the autologous fascial sling. No statistical impact was noted with sling excision (P = 0.62), mixed urinary incontinence (P = 0.61), age at surgery (P = 0.23), age at follow up (P = 0.15), length of follow up (P = 0.71) or first surgery type (transobturator tape vs retropubic; P = 1.00). CONCLUSIONS: Autologous fascial sling provides reasonable long-term success as a salvage operation for failed midurethral slings. PMID- 26563493 TI - Postpartum adverse effects and sexual satisfaction following cesarean delivery in Beijing. AB - OBJECTIVE: To investigate short- and long-term postpartum complications of different delivery methods in terms of sexual satisfaction, stress urinary incontinence (SUI), and pelvic-floor dysfunction in the Beijing region. METHODS: A questionnaire-based study was conducted between June 30, 2013 and July 1, 2014. Female residents of Beijing aged 20-65 years, who were attending routine physical examinations, were enrolled and completed a face-to-face survey including questions on short- and long-term complications related to sexual satisfaction, SUI, and pelvic-floor dysfunction postpartum. RESULTS: In total, 2649 individuals were enrolled. In comparison with patients that underwent vaginal delivery, patients that had undergone cesarean delivery experienced a greater length of time before resuming intercourse (2.70+/-2.0 9months vs 4.32+/-4.10 months; P<0.001) and higher incidences of decreased libido (93 [6.1%] vs 234 [20.7%]; P<0.001), vaginal dryness (39 [2.6%] vs 177 [15.7%]; P<0.001), sexual dissatisfaction (117 [7.7%] vs 234 [20.7%]; P<0.001), and painful intercourse (48 [3.2%] vs 252 [22.3%]; P<0.001) after delivery. Cesarean delivery did not demonstrate any long-term protective effects against future SUI in comparison with vaginal delivery. CONCLUSION: Cesarean delivery resulted in a greater incidence of adverse effects on postpartum sexual function and cesarean delivery provides no long-term protective effects against postpartum SUI. PMID- 26563494 TI - Fiber-optic control and thermometry of single-cell thermosensation logic. AB - Thermal activation of transient receptor potential (TRP) cation channels is one of the most striking examples of temperature-controlled processes in cell biology. As the evidence indicating the fundamental role of such processes in thermosensation builds at a fast pace, adequately accurate tools that would allow heat receptor logic behind thermosensation to be examined on a single-cell level are in great demand. Here, we demonstrate a specifically designed fiber-optic probe that enables thermal activation with simultaneous online thermometry of individual cells expressing genetically encoded TRP channels. This probe integrates a fiber-optic tract for the delivery of laser light with a two-wire microwave transmission line. A diamond microcrystal fixed on the fiber tip is heated by laser radiation transmitted through the fiber, providing a local heating of a cell culture, enabling a well-controlled TRP-assisted thermal activation of cells. Online local temperature measurements are performed by using the temperature-dependent frequency shift of optically detected magnetic resonance, induced by coupling the microwave field, delivered by the microwave transmission line, to nitrogen--vacancy centers in the diamond microcrystal. Activation of TRP channels is verified by using genetically encoded fluorescence indicators, visualizing an increase in the calcium flow through activated TRP channels. PMID- 26563495 TI - Carrier testing in children and adolescents. AB - Many international guidelines recommend that carrier testing in minors should be postponed either until the age of majority or until the child can be actively involved in the decision making process. Although a number of high school programs exist which provide carrier screening to adolescents in at-risk populations, recent guidelines published by the American Society of Human Genetics do not advocate this testing. Despite this, there are some circumstances in which carrier testing does occur in minors. This testing might be intentional, in which identification of carrier status is the goal of the test, or unintentional, where carrier status is identified as a by-product of testing. In this review we outline the situations in which carriers may be identified in childhood and the positions of professional guidelines that address carrier testing in children. We then review the arguments for and against carrier testing presented in the literature and compare this to the empirical evidence in this field. PMID- 26563496 TI - Two rare deletions upstream of the NRXN1 gene (2p16.3) affecting the non-coding mRNA AK127244 segregate with diverse psychopathological phenotypes in a family. AB - CNVs spanning the 2p16.3 (NRXN1) and the 15q11.2 gene rich region have been associated with severe neuropsychiatric disorders including schizophrenia. Recently, studies have also revealed that CNVs in non-coding regions play an essential role in genomic variability in addition to disease susceptibility. In this study, we describe a family affected by a wide range of psychiatric disorders including early onset schizophrenia, schizophreniform disorder, and affective disorders. Microarray analysis identified two rare deletions immediately upstream of the NRXN1 gene affecting the non-coding mRNA AK127244 in addition to the pathogenic 15q11.2 deletion in distinct family members. The two deletions upstream of the NRXN1 gene were found to segregate with psychiatric disorders in the family and further similar deletions have been observed in patients diagnosed with autism spectrum disorder. Thus, we suggest that non coding regions upstream of the NRXN1 gene affecting AK127244 might (as NRXN1) contain susceptibility regions for a wide spectrum of neuropsychiatric disorders. PMID- 26563497 TI - Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia. AB - The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1beta (IL 1beta), and tumor necrosis factor-alpha (TNF-alpha) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-kappaB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis. PMID- 26563500 TI - Recent increases in nitrogen oxide (NOx) emissions from coal-fired electric generating units equipped with selective catalytic reduction. AB - The most effective control technology available for the reduction of oxides of nitrogen (NOx) from coal-fired boilers is selective catalytic reduction (SCR). Installation of SCR on coal-fired electric generating units (EGUs) has grown substantially since the onset of the U.S. Environmental Protection Agency's (EPA) first cap and trade program for oxides of nitrogen in 1999, the Ozone Transport Commission (OTC) NOx Budget Program. Installations have increased from 6 units present in 1998 in the states that encompass the current Cross-State Air Pollution Rule (CSAPR) ozone season program to 250 in 2014. In recent years, however, the degree of usage of installed SCR technology has been dropping significantly at individual plants. Average seasonal NOx emission rates increased substantially during the Clean Air Interstate Rule (CAIR) program. These increases coincided with a collapse in the cost of CAIR allowances, which declined to less than the cost of the reagent required to operate installed SCR equipment, and was accompanied by a 77% decline in delivered natural gas prices from their peak in June of 2008 to April 2012, which in turn coincided with a 390% increase in shale gas production between 2008 and 2012. These years also witnessed a decline in national electric generation which, after peaking in 2007, declined through 2013 at an annualized rate of -0.3%. Scaling back the use of installed SCR on coal-fired plants has resulted in the release of over 290,000 tons of avoidable NOx during the past five ozone seasons in the states that participated in the CAIR program. IMPLICATIONS: To function as designed, a cap and trade program must maintain allowance costs that function as a disincentive for the release of the air pollutants that the program seeks to control. If the principle incentive for reducing NOx emissions is the avoidance of allowance costs, emissions may be expected to increase if costs fall below a critical value, in the absence of additional state or federal limitations. As such, external factors as the cost of competing fuels and a low or negative growth of electric sales may also disincentivize the use of control technologies, the continuation of desirable emission rates will be best maintained by the implementation of performance standards that supplement and complement the emissions trading program. PMID- 26563498 TI - N-Methyl, N-propynyl-2-phenylethylamine (MPPE), a Selegiline Analog, Attenuates MPTP-induced Dopaminergic Toxicity with Guaranteed Behavioral Safety: Involvement of Inhibitions of Mitochondrial Oxidative Burdens and p53 Gene-elicited Pro apoptotic Change. AB - Selegiline is a monoamine oxidase-B (MAO-B) inhibitor with anti-Parkinsonian effects, but it is metabolized to amphetamines. Since another MAO-B inhibitor N Methyl, N-propynyl-2-phenylethylamine (MPPE) is not metabolized to amphetamines, we examined whether MPPE induces behavioral side effects and whether MPPE affects dopaminergic toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Multiple doses of MPPE (2.5 and 5 mg/kg/day) did not show any significant locomotor activity and conditioned place preference, whereas selegiline (2.5 and 5 mg/kg/day) significantly increased these behavioral side effects. Treatment with MPPE resulted in significant attenuations against decreases in mitochondrial complex I activity, mitochondrial Mn-SOD activity, and expression induced by MPTP in the striatum of mice. Consistently, MPPE significantly attenuated MPTP-induced oxidative stress and MPPE-mediated antioxidant activity appeared to be more pronounced in mitochondrial-fraction than in cytosolic-fraction. Because MPTP promoted mitochondrial p53 translocation and p53/Bcl-xL interaction, it was also examined whether mitochondrial p53 inhibitor pifithrin-MU attenuates MPTP neurotoxicity. MPPE, selegiline, or pifithrin-MU significantly attenuated mitochondrial p53/Bcl-xL interaction, impaired mitochondrial transmembrane potential, cytosolic cytochrome c release, and cleaved caspase-3 in wild-type mice. Subsequently, these compounds significantly ameliorated MPTP-induced motor impairments. Neuroprotective effects of MPPE appeared to be more prominent than those of selegiline. MPPE or selegiline did not show any additional protective effects against the attenuation by p53 gene knockout, suggesting that p53 gene is a critical target for these compounds. Our results suggest that MPPE possesses anti-Parkinsonian potentials with guaranteed behavioral safety and that the underlying mechanism of MPPE requires inhibition of mitochondrial oxidative stress, mitochondrial translocation of p53, and pro-apoptotic process. PMID- 26563501 TI - Towards "next-generation" prostate cancer screening. PMID- 26563499 TI - Parkin Protects Against Misfolded SOD1 Toxicity by Promoting Its Aggresome Formation and Autophagic Clearance. AB - Mutations in Cu/Zn superoxide dismutase (SOD1) cause autosomal dominant amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease with no effective treatment. Despite ample evidence indicating involvement of mutation induced SOD1 protein misfolding and aggregation in ALS pathogenesis, the molecular mechanisms that control cellular management of misfolded, aggregation prone SOD1 mutant proteins remain unclear. Here, we report that parkin, an E3 ubiquitin-protein ligase which is linked to Parkinson's disease, is a novel regulator of cellular defense against toxicity induced by ALS-associated SOD1 mutant proteins. We find that parkin mediates K63-linked polyubiquitination of SOD1 mutants in cooperation with the UbcH13/Uev1a E2 enzyme and promotes degradation of these misfolded SOD1 proteins by the autophagy-lysosome system. In response to strong proteotoxic stress associated with proteasome impairment, parkin promotes sequestration of misfolded and aggregated SOD1 proteins to form perinuclear aggresomes, regulates positioning of lysosomes around misfolded SOD1 aggresomes, and facilitates aggresome clearance by autophagy. Our findings reveal parkin-mediated cytoprotective mechanisms against misfolded SOD1 toxicity and suggest that enhancing parkin-mediated cytoprotection may provide a novel therapeutic strategy for treating ALS. PMID- 26563502 TI - Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study. AB - BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50-69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406. FINDINGS: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0.0001), the area under the curve was 0.56 (95% CI 0.55-0.60) with PSA alone and 0.74 (95% CI 0.72-0.75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0.05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of >=3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24-39) and could avoid 44% (35-54) of benign biopsies. INTERPRETATION: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. FUNDING: Stockholm County Council (Stockholms Lans Landsting). PMID- 26563503 TI - Model-based approaches for ivabradine development in paediatric population, part I: study preparation assessment. AB - The main objective was to help design a paediatric study for ivabradine, a compound already marketed in adults, focusing on: the paediatric formulation evaluation, the doses to be administered, the sampling design and the sampling technique. A secondary objective was to perform a comparison of the prediction of ivabradine pharmacokinetics (PK) in children using a physiologically-based pharmacokinetic (PBPK) approach and allometric scaling of a population pharmacokinetic (PPK) model. A study was conducted in order to assess the relative bioavailability (Frel) of the paediatric formulation and a similar Frel was observed between the paediatric formulation and the adult marketed tablet. PBPK modelling was used to predict initial doses to be administered in the paediatric study and to select the most appropriate sample time collections. The dried blood spot technique was recommended in the clinical trial in children. Simulations obtained by both the PBPK approach and allometric scaling of a PPK model were compared a posteriori to the paediatric study observations. Both PPK and PBPK approaches allowed an adequate prediction of the PK of ivabradine and its metabolite in children. PMID- 26563504 TI - Application of a hazard-based visual predictive check to evaluate parametric hazard models. AB - Parametric models used in time to event analyses are evaluated typically by survival-based visual predictive checks (VPC). Kaplan-Meier survival curves for the observed data are compared with those estimated using model-simulated data. Because the derivative of the log of the survival curve is related to the hazard- the typical quantity modeled in parametric analysis--isolation, interpretation and correction of deficiencies in the hazard model determined by inspection of survival-based VPC's is indirect and thus more difficult. The purpose of this study is to assess the performance of nonparametric hazard estimators of hazard functions to evaluate their viability as VPC diagnostics. Histogram-based and kernel-smoothing estimators were evaluated in terms of bias of estimating the hazard for Weibull and bathtub-shape hazard scenarios. After the evaluation of bias, these nonparametric estimators were assessed as a method for VPC evaluation of the hazard model. The results showed that nonparametric hazard estimators performed reasonably at the sample sizes studied with greater bias near the boundaries (time equal to 0 and last observation) as expected. Flexible bandwidth and boundary correction methods reduced these biases. All the nonparametric estimators indicated a misfit of the Weibull model when the true hazard was a bathtub shape. Overall, hazard-based VPC plots enabled more direct interpretation of the VPC results compared to survival-based VPC plots. PMID- 26563505 TI - Clinicopathological characteristics of Xp11.2 translocation renal cell carcinoma in adolescents and adults: Diagnosis using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis. AB - OBJECTIVES: To determine the rate and clinicopathological features of Xp11.2 translocation carcinoma using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis. METHODS: We evaluated 638 patients with renal cell carcinoma treated at Sapporo Medical University Hospital, Sapporo, Japan, from 1990 to 2009 by reviewing all hematoxylin-eosin-stained sections and carrying out immunostaining of transcription factor E3 for all cases. Fluorescence in situ hybridization analysis was carried out for patients with positive immunostaining or with findings suspicious for Xp11.2 translocation carcinoma on hematoxylin-eosin-stained sections. In this analysis, we set a cut off level for split signals of at least 10% of nuclei. RESULTS: Of the 631 patients, 20 (3.2%) were positive for immunostaining. Finally, five patients were diagnosed with Xp11.2 translocation carcinoma (0.8%). Four of these patients were female and aged less than 50 years, and three cases were diagnosed as stage IV with multiple regional lymph nodal or visceral metastases. The positive predictive value of immunostaining was 25%. CONCLUSION: Patients with Xp11 translocation renal cell carcinoma tend to be younger, more frequently female and diagnosed at a more advanced stage. Immunostaining followed by fluorescence in situ hybridization analysis is an accurate and cost-effective approach for diagnosis of Xp11 translocation renal cell carcinoma. PMID- 26563506 TI - Introduction to "Monolithic columns in high-performance liquid chromatography" by G. Guiochon [J. Chromatogr. A 1168 (2007) 101-168]. PMID- 26563507 TI - Plant-mediated interspecific horizontal transmission of an intracellular symbiont in insects. AB - Intracellular reproductive manipulators, such as Candidatus Cardinium and Wolbachia are vertically transmitted to progeny but rarely show co-speciation with the host. In sap-feeding insects, plant tissues have been proposed as alternative horizontal routes of interspecific transmission, but experimental evidence is limited. Here we report results from experiments that show that Cardinium is horizontally transmitted between different phloem sap-feeding insect species through plants. Quantitative PCR and in situ hybridization experiments indicated that the leafhopper Scaphoideus titanus releases Cardinium from its salivary glands during feeding on both artificial media and grapevine leaves. Successional time-course feeding experiments with S. titanus initially fed sugar solutions or small areas of grapevine leaves followed by feeding by the phytoplasma vector Macrosteles quadripunctulatus or the grapevine feeder Empoasca vitis revealed that the symbionts were transmitted to both species. Explaining interspecific horizontal transmission through plants improves our understanding of how symbionts spread, their lifestyle and the symbiont-host intermixed evolutionary pattern. PMID- 26563508 TI - Impact of artificial capnothorax on coagulation in patients during video-assisted thoracoscopic esophagectomy for squamous cell carcinoma. AB - BACKGROUND: Compared with the lung isolation using double-lumen endobronchial tube intubation, the artificial capnothorax using single-lumen endotracheal tube intubation has shown to be a safe, more convenient, and cost-effective procedure for thoracoscopic esophagectomy. However, the impact of capnothorax on coagulation is not well defined. Herein, we evaluate the impact of a capnothorax on coagulation and fibrinolysis in patients who undergoing thoracoscopic esophagectomy. METHODS: Between March 2014 and August 2014, 24 patients underwent thoracoscopic esophagectomies for esophageal cancer with the procedure of artificial capnothorax (group P); we also performed 24 thoracoscopic esophagectomy cases without using capnothorax (group N). The demographics and arterial blood gas, as well as the parameters of coagulation and fibrinolysis, of the two groups were analyzed. RESULTS: The pH value of group P after CO2 insufflation was significantly lower than in group N (P < 0.05), and the partial pressure of carbon dioxide (PaCO2) was significantly increased compared with group N (P < 0.05). The R and K values after CO2 insufflation were significantly longer than before anesthesia (P < 0.05), and both alpha angle and MA value after CO2 insufflation were significantly lower than those before anesthesia (P < 0.05). No significant differences in R value, K value, alpha angle, or MA value were observed between pre-anesthesia and termination of capnothorax. No significant difference in LY30 data was found between different groups (P > 0.05). CONCLUSION: Artificial capnothorax in patients receiving endoscopic resection of esophageal carcinoma had a significant impact on coagulation. These patients showed significant impairments in coagulation not observed in patients without artificial capnothorax. PMID- 26563509 TI - A scoring system for patients with a tumor-positive lateral resection margin after endoscopic resection of early gastric cancer. AB - BACKGROUND: The aim of this study was to identify the risk factors for residual/recurrent tumors in patients with a tumor-positive lateral resection margin (LRM+) after endoscopic resection of early gastric cancer (EGC) and to establish the criteria for performing additional treatment. METHODS: A retrospective analysis was performed on consecutive patients who underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of EGC. Clinicopathological characteristics and risk factors for residual/recurrent tumor in LRM+ patients were analyzed. RESULTS: Eighty-two patients (84 lesions) with LRM+ after EMR (n = 45) or ESD (n = 39) were enrolled. Forty patients underwent additional gastrectomy or ESD, and 44 were closely observed. The residual/recurrent tumor rate was 34.5 % (29 of 84 lesions). Univariate analysis found that the residual/recurrent tumor was associated with the endoscopic resection type (EMR), undifferentiated histology, number of involved directions, rate of lateral resection margin involvement and the total length (mm) of the lateral resection margin involved by the tumor. In multivariate logistic regression analysis, undifferentiated histology and rate (%) were independent risk factors (odds ratio [OR] 5.28, 95 % confidence interval [CI] 1.13-24.72, p = 0.035 and OR 1.08, 95 % CI 1.03-1.14, p = 0.004, respectively). Clinicopathological factors that were identified from the univariate and multivariate analyses were scored in order to predict residual/recurrent tumors. CONCLUSION: We suggest a scoring system for additional treatment in patients with LRM+ after endoscopic resection of EGC based on the development of residual/recurrent tumors. This scoring system enables a more detailed selection of cases and may be useful in determining further treatment. PMID- 26563512 TI - Question 6: Is there a role for Mannose-Binding Lectin measurement in Cystic Fibrosis management? PMID- 26563511 TI - Sustaining large-scale infrastructure to promote pre-competitive biomedical research: lessons from mouse genomics. AB - Bio-repositories and databases for biomedical research enable the efficient community-wide sharing of reagents and data. These archives play an increasingly prominent role in the generation and dissemination of bioresources and data essential for fundamental and translational research. Evidence suggests, however, that current funding and governance models, generally short-term and nationally focused, do not adequately support the role of archives in long-term, transnational endeavours to make and share high-impact resources. Our qualitative case study of the International Knockout Mouse Consortium and the International Mouse Phenotyping Consortium examines new governance mechanisms for archive sustainability. Funders and archive managers highlight in interviews that archives need stable public funding and new revenue-generation models to be sustainable. Sustainability also requires archives, journal publishers, and funders to implement appropriate incentives, associated metrics, and enforcement mechanisms to ensure that researchers use archives to deposit reagents and data to make them publicly accessible for academia and industry alike. PMID- 26563513 TI - Evaluation of upper airway obstruction in infants with Pierre Robin sequence and the role of polysomnography--Review of current evidence. AB - Pierre Robin sequence (PRS) is a heterogeneous condition presenting with upper airway obstruction (UAO) of varying severity. Polysomnography (PSG) is an objective investigation to assess the severity of obstructive sleep apnea and UAO. Its role in the management of PRS has not been well defined. This review summarizes the available evidence on the role of PSG in the assessment of infants with PRS in the context of other commonly used methods of assessment. PMID- 26563510 TI - Effect of nanostructured thin film on minimally invasive surgery devices applications: characterization, cell cytotoxicity evaluation and an animal study in rat. AB - BACKGROUND: Minimally invasive surgery is performed using an endoscope and other instruments including the electrosurgical units. However, concerns including surgical smoke, tissue sticking and thermal injury are remaining in electrosurgery. AIMS: Accordingly, a newly developed electrosurgical electrode coating with hydrogenated Cu-incorporated diamond-like carbon (DLC-Cu) film is purposed to improve the instrument performance. METHODS: The morphologies of DLC Cu surfaces were characterized using transmission electron microscopy, scanning electron microscopy and atomic force microscopy. In this study, lesions were made on the liver lobes of adult rats, using a monopolar electrosurgical unit equipped with untreated stainless steel electrodes or treated-electrodes. Animals were killed for evaluations at 0, 3, 7 and 28 days postoperatively. RESULTS: Treated electrodes generate less sticking tissues and adhesive blood cells. Thermography revealed that the surgical temperature in liver tissue from the treated-electrode was significantly lower than the untreated-electrode. Total injury area of livers treated with treated-electrodes was significantly smaller than the untreated electrodes treatment. Moreover, treated-electrodes caused a relatively smaller area of lateral thermal injury, a smaller area of fibrotic tissue and a faster process of remodeling than the untreated-electrodes. Western blot analysis showed that rats treated with treated-electrode expressed lower levels of NF-kappaB, caspase-3 and MMP-9 than untreated-electrode. Immunofluorescence staining for caspase-3 revealed that the untreated-electrode caused more serious injury. CONCLUSIONS: This study reveals that the plating of electrodes with hydrogenated Cu-incorporated diamond-like carbon film is an efficient method for improving the performance of electrosurgical units, and should benefit wound remodeling. However, more tests must be carried out to confirm these promising findings in human patients. PMID- 26563514 TI - Can daytime measures of lung function predict respiratory failure in children with neuromuscular disease? AB - Neuromuscular disorders in children are a heterogeneous group of conditions with a variable age of presentation and overlapping clinical manifestations, many of which have progressive respiratory morbidity. Respiratory insufficiency occurs as a consequence of an imbalance between demands on the respiratory system and respiratory muscle capacity. Daytime measures of pulmonary function are used routinely in these children to assess respiratory status and monitor the consequences of the progression of muscle weakness. This review describes the current evidence for daytime pulmonary function tests and their ability to predict imminent respiratory morbidity. PMID- 26563515 TI - Sun exposure risk in children: the Italian paediatrician perspective. PMID- 26563516 TI - Digital quantum simulators in a scalable architecture of hybrid spin-photon qubits. AB - Resolving quantum many-body problems represents one of the greatest challenges in physics and physical chemistry, due to the prohibitively large computational resources that would be required by using classical computers. A solution has been foreseen by directly simulating the time evolution through sequences of quantum gates applied to arrays of qubits, i.e. by implementing a digital quantum simulator. Superconducting circuits and resonators are emerging as an extremely promising platform for quantum computation architectures, but a digital quantum simulator proposal that is straightforwardly scalable, universal, and realizable with state-of-the-art technology is presently lacking. Here we propose a viable scheme to implement a universal quantum simulator with hybrid spin-photon qubits in an array of superconducting resonators, which is intrinsically scalable and allows for local control. As representative examples we consider the transverse field Ising model, a spin-1 Hamiltonian, and the two-dimensional Hubbard model and we numerically simulate the scheme by including the main sources of decoherence. PMID- 26563517 TI - Increased alpha1-3 fucosylation of alpha-1-acid glycoprotein (AGP) in pancreatic cancer. AB - Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important challenge. Previous results looking at a small cohort of patients showed an increase in alpha-1-acid glycoprotein (AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here, we have analysed AGP glycoforms in a larger cohort using several analytical techniques including mass spectrometry (MS), capillary zone electrophoresis (CZE) and enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31 serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic hydrophilic interaction capillary liquid chromatography electrospray MS (MUZIC-HILIC-ESI-MS) showed an increase in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that alpha1-3 fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker. PMID- 26563518 TI - Purification and Characterization of Catechol 1,2-Dioxygenase from Acinetobacter sp. Y64 Strain and Escherichia coli Transformants. AB - This study intends to purify and characterize catechol 1,2-dioxygenase (C1,2O) of phenol-degrading Acinetobacter sp. Y64 and of E. coli transformant. Acinetobacter sp. Y64 was capable of degrading 1000 mg/L of phenol within 14 +/- 2 h at 30 degrees C, 160 rpm and pH of 7. One C1,2O of 36 kDa was purified using ammonium sulphate precipitation and Hitrap QFF column chromatograph with 49% recovery and a 10.6-fold increase in purity. Purified Y64 C1,2O had temperature and pH optimum at 37 degrees C and pH 7.7 respectively with the Michaelis constant of 17.53 uM and the maximal velocity of 1.95 U/mg, respectively. The presence of Fe(3+) or Fe(2+) enhanced the activity of Y64 C1,2O while other compounds such as Ca(2+), and EDTA had an inhibitory effect. 80% of C1,2O activity remained using 4 nitrocatechol as substrate while 2% remained using 3-methylcatechol compared with that using catechol. Y64 catA gene encoding C1,2O was amplified using PCR cloned into pET22b vector and expressed in Escherichia coli BL21 DE3 (pLysS) after transformation. Purified and cloned Y64 C1,2O show no significant differences in the biochemical properties. The phylogenetic tree based on the protein sequences indicates that these C1,2Os possess a common ancestry. PMID- 26563520 TI - Magnetic field-dependent shape anisotropy in small patterned films studied using rotating magnetoresistance. AB - Based on the electric rotating magnetoresistance method, the shape anisotropy of a Co microstrip has been systematically investigated. We find that the shape anisotropy is dependent not only on the shape itself, but also on the magnetization distribution controlled by an applied magnetic field. Together with micro-magnetic simulations, we present a visualized picture of how non-uniform magnetization affects the values and polarities of the anisotropy constants K1 and K2. From the perspective of potential appliantions, our results are useful in designing and understanding the performance of micro- and nano-scale patterned ferromagnetic units and the related device properties. PMID- 26563519 TI - Moisturizers are effective in the treatment of xerosis irrespectively from their particular formulation: results from a prospective, randomized, double-blind controlled trial. AB - BACKGROUND: Many companies claim that their moisturizers are superior to others based on their ingredients. OBJECTIVE: To compare the efficacy and safety of the most popular moisturizers in the field. METHODS: A randomized, double-blind, controlled study was performed on 80 patients with moderate to severe xerosis. The test agents included the newly developed cream containing topical recombinant human epidermal growth factor (EGF), its vehicle without EGF and four additional therapeutic moisturizers. The study subjects applied the test agents on designated skin areas twice daily for 4 weeks. All of the clinical assessments and non-invasive objective measurements were performed at baseline, and on days 14 and 28 of the study. RESULTS: All of the test agents significantly improved the clinical symptoms of xerosis. The biophysical parameters similarly improved from baseline (P < 0.05). None of the test agents performed significantly better than did another. CONCLUSION: In the treatment of xerosis, consistent and regular moisturizer use is much more important than the moisturizer's particular formulation. PMID- 26563521 TI - Foreword to Defining the Role of Social Sciences in Patient Safety. PMID- 26563522 TI - OSAS in Specific Pediatric Populations. PMID- 26563524 TI - Clinical and economic consequences of first-year urinary tract infections, sepsis, and pneumonia in contemporary kidney transplantation practice. AB - We examined United States Renal Data System registry records for Medicare-insured kidney transplant recipients in 2000-2011 to study the clinical and cost impacts of urinary tract infections (UTI), pneumonia, and sepsis in the first year post transplant among a contemporary, national cohort. Infections were identified by billing diagnostic codes. Among 60 702 recipients, 45% experienced at least one study infection in the first year post-transplant, including UTI in 32%, pneumonia in 13%, and sepsis in 12%. Older recipient age, female sex, diabetic kidney failure, nonstandard criteria organs, sirolimus-based immunosuppression, and steroids at discharge were associated with increased risk of first-year infections. By time-varying, multivariate Cox regression, all study infections predicted increased first-year mortality, ranging from 41% (aHR 1.41, 95% CI 1.25 1.56) for UTI alone, 6- to 12-fold risk for pneumonia or sepsis alone, to 34-fold risk (aHR 34.38, 95% CI 30.35-38.95) for those with all three infections. Infections also significantly increased first-year costs, from $17 691 (standard error (SE) $591) marginal cost increase for UTI alone, to approximately $40 000 $50 000 (SE $1054-1238) for pneumonia or sepsis alone, to $134 773 (SE $1876) for those with UTI, pneumonia, and sepsis. Clinical and economic impacts persisted in years 2-3 post-transplant. Early infections reflect important targets for management protocols to improve post-transplant outcomes and reduce costs of care. PMID- 26563525 TI - Evaluation of postoperative anal functions using endoanal ultrasonography and anorectal manometry in children with congenital anorectal malformations. AB - PURPOSE: The aim of this study was to assess the postoperative anorectal anatomy and function in children with congenital anorectal malformations (ARM) using endoanal ultrasonography (EUS) and anorectal manometry. METHODS: This study included 47 children who had undergone posterior sagittal anorectoplasty (PSARP) or transperineal anorectoplasty for the repair of an ARM. Children were grouped according to symptoms of defecation disorder, including normal defecation, fecal soiling, fecal incontinence, and constipation. Ten children with no history of anal or rectal diseases served as healthy controls. A well-established scoring system was used for the evaluation of anal function and defecation disorder. RESULTS: EUS showed significant differences in the thickness of the interior sphincter between the ARM patients and the healthy controls (P<0.05). However, no significant difference was found in the thickness of the interior sphincters between the PSARP group and transperineal anorectoplasty group (P>0.05). Anorectal manometry showed that the balloon volumes were significantly different between the surgical group and the control group (P<0.01), and between the low defect group and the intermediate-high defect group (P=0.022). Balloon volume was significantly correlated with anal function scores (r=-0.30, P<0.05). CONCLUSIONS: EUS and anorectal manometry can provide objective assessment of postoperative anorectal anatomy and function in children with ARM. PMID- 26563526 TI - Risk factors and management of Nuss bar infections in 1717 patients over 25 years. AB - PURPOSE: An increase in postoperative infections after Nuss procedures led us to seek risks and review management. We report potential risk factors and make inferences for prevention of infections. METHODS: An IRB-approved retrospective chart review was used to evaluate demographic, clinical, surgical, and postoperative variables of patients operated on between 10/1/2005 and 6/30/2013. Those with postoperative infection were evaluated for infection characteristics, management, and outcomes with univariate analyses. RESULTS: Over this 8-year period (2005-2013), 3.5% (30) of 854 patients developed cellulitis or infection, significantly more than 1.5% (13) in our previous report of 863 patients, 1987 2005 (p=.007). The most frequent organism cultured was methicillin-sensitive Staphylococcus aureus. Patients who were given clindamycin preoperatively (5 of 26 patients) had higher infection rates than those who received cefazolin (25 of 828) (19% vs 3%, p<.001). Patients treated with a peri-incisional ON-Q (I-Flow, Kimberly-Clark, Irvine, CA) also had higher infection rates (8.3% vs 2.4%, p<.001). Of the 30 patients who developed an infection, eighteen (60%) with cellulitis or superficial infections did not require surgical treatment or early bar removal. The other twelve patients (40%) with deep hardware infections required an average of 2.2 operations (range 1-6), with 3 (25%) requiring removal of their stabilizer and 3 (25%) requiring early bar removal. None of these three patients experienced recurrence of pectus excavatum at 2 to 4 years of follow-up. CONCLUSION: Preoperative antibiotic selection and use of ON-Q's may influence infection rates after Nuss repair. Nuss bars could be preserved in 90% of all patients with an infection and even 75% of those with a deep hardware infection. Attempts to retain the bar when an infection occurs may help prevent pectus excavatum recurrence. Level of Evidence=III. PMID- 26563527 TI - The anatomic findings during operative exploration for non-palpable testes: A prospective evaluation. AB - BACKGROUND: We conducted a randomized trial comparing 1 and 2-stage laparoscopic orchiopexy for intra-abdominal testes. During recruitment, it became apparent that most patients with non-palpable testes do not require vascular division. In this report, we outline the location and quality of testes found during operative exploration in patients who consented for the study but were not randomized. METHODS: Analysis was performed on 80 patients undergoing operative exploration for non-palpable testes between 2007 and 2014. The location and pathology of undescended testes were analyzed. RESULTS: There were 87 preoperative non palpable testes in 80 patients that were consented but not randomized to 1 or 2 stage orchiopexy with vascular division. Forty (46%) of nonrandomized testes were atrophic or absent, and 47 (54%) were normal in appearance. Sixty eight testes were evaluated via laparoscopy. The most common location for normal (81%) and absent/atrophic (70%) testes was the inguinal canal. Atrophic testes were more often left sided (72.5%) with normal testes equally divided. Patients with atrophic or absent testicles were more likely to have a closed internal ring (p<0.01). CONCLUSION: This study demonstrates the majority of patients undergoing operative exploration for non-palpable testes will not require vascular division, and instead would be either atrophic or able to undergo traditional orchiopexy. LEVEL OF EVIDENCE: III. PMID- 26563528 TI - Documentation of pediatric vital signs by EMS providers over time. AB - BACKGROUND: Pediatric patients make up approximately 10% of EMS transports nationwide. Previous studies demonstrated that pediatric patients do not consistently have a full set of vitals signs obtained in the prehospital setting [1]. In certain conditions, such as traumatic head injury and shock, unrecognized hypotension and/or hypoxia are associated with increased morbidity and mortality [2,3]. OBJECTIVES: PRIMARY OBJECTIVE: To measure how often EMS providers obtain blood pressure (BP), heart rate (HR), pulse oximetry (Po), and respiratory rate (RR) on pediatric transport patients in the state of Utah from 2007 to 2014. SECONDARY OBJECTIVE: To assess whether educational interventions improved the percentage of pediatric transport patients with a full set of vital signs documented. RESULTS: The trend of documenting the four critical vital signs improved over time for all four categories. Measurement of Po increased most consistently across all age groups. Blood pressure remained the most inconsistently obtained vital sign, especially in younger pediatric patients. The educational interventions introduced in late 2010 correlated with an increase in vital sign attainment. CONCLUSIONS: Assessment of pediatric vitals signs is a critical part of the evaluation and care of pediatric patients in the prehospital setting. Utah EMS providers improved their practice of documenting four pediatric vital signs over time after educational interventions. Obtaining a BP, especially in younger children, continues to be a challenge. More work remains to achieve the state goal of documenting all vital signs in >90% of pediatric transports. PMID- 26563529 TI - Early reported rectal sensation predicts continence in anorectal anomalies. AB - BACKGROUND: Straining at stool is an automatic reflex in babies and implies the presence of rectal sensation. We hypothesised that early reported rectal sensation would predict future continence in children with anorectal anomalies. AIM OF THE STUDY: The aim of this study is to determine if early straining at stool was a useful predictor of future continence in infants born with high anorectal malformations. METHODS: A retrospective case note review of prospectively collected clinical information was performed with institutional review board approval. All patients with intermediate/high anorectal malformation operated on by a single surgeon from 1984 to 2010 were included. After stoma closure, parents were asked: The responses were noted within the first year of stoma closure and then all patients were followed up until they were at least 3 1/2years old and continence could be assessed using the Krickenbeck outcome classification. Data were compared using Fisher's exact test and sensitivity, specificity and positive predictive value (PPV) were calculated. MAIN RESULTS: Forty-eight patients were included in the study. Sixteen (33%) were female (12 cloacal malformation, 3 rectovaginal fistula, 1 rectal atresia) and 32 (66%) were male (6 rectovesical fistulae, 22 rectourethral fistulae, 4 no fistula). Median follow-up was 9.7years (range 3.5-17.9). Twenty-one children were noted by their parents to exhibit early straining at stool after stoma closure. Twenty of them achieved long term continence. The sensitivity of early straining as a predictor for long term continence was 77%, specificity 95% and positive predictive value 95%. CONCLUSION: The presence of early rectal sensation reported by parents is a good predictor of long term continence. This allows more informed discussion with families in the early years of life. PMID- 26563530 TI - Risk-stratification of severity for infants with CDH: Prenatal versus postnatal predictors of outcome. AB - PURPOSE: The purpose of this study was to compare the predication accuracy of a newly described postnatally-based clinical prediction model to fetal imaging based predictors of mortality for infants with CDH. METHODS: We performed a retrospective review of all CDH patients treated at a comprehensive fetal care center from January 2004 to January 2014. Prenatal data reviewed included lung-to head ratio (LHR), observed/expected-total fetal lung volume (O/E-TFLV), and percent liver herniation (%LH). Based on the postnatal prediction model, neonates were categorized as low, intermediate, and high risk of death. The primary outcome was 6-month mortality. RESULTS: Of 176 CDH patients, 58 had a major cardiac anomaly, and 28 had a genetic anomaly. Patients with O/E-TFLV <35% and %LH >20% were at increased risk for mortality (44% and 36%, respectively). There was a significant difference in mortality between low, intermediate, and high risk groups (4% vs. 22% vs. 51%; p<0.001). On multivariate regression, the O/E TFLV and postnatal-based mortality risk score were the two independent predictors of 6-month mortality. CONCLUSION: The CDH Study Group postnatal predictive model provides good discrimination among three risk groups in our patient cohort. The prenatal MRI-based O/E-TFLV is the strongest prenatal predictor of 6-month mortality in infants with CDH and will help guide prenatal counseling and discussions regarding fetal intervention and perinatal management. PMID- 26563531 TI - Optimized donor management and organ preservation before kidney transplantation. AB - Kidney transplantation is a major medical improvement for patients with end-stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune-mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro-inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long-term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single-center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long-term results after kidney transplantation. PMID- 26563532 TI - Trends in High Blood Pressure among United States Adolescents across Body Weight Category between 1988 and 2012. AB - OBJECTIVE: To examine trends in pre-high blood pressure (BP [HBP]) and HBP among US adolescents by body weight category during 1988-2012. STUDY DESIGN: We estimated pre-HBP and HBP prevalence among 14,844 participants aged 12-19 years using National Health and Nutrition Examination Surveys from 1988-1994, 1999 2002, 2003-2006, and 2007-2012. Pre-HBP and HBP were defined based on age-sex height-specific BP percentiles. We examined the temporal trends in pre-HBP and HBP across category of body weight (normal weight vs overweight/obese), adjusted for potential explanatory factors, and estimated the number of adolescents with pre-HBP and HBP. RESULTS: Between 1988 and 2012, the prevalence of HBP decreased and pre-HBP did not change. Among normal weight adolescents, multivariable adjusted pre-HBP prevalence was 11.0% during 1988-2012, and 10.9% during 2007 2012 (P = .923 for trend); adjusted HBP prevalence increased from 1988-1994 (0.9%) to 1999-2002 (2.3%), then declined significantly to 1.4% during 2007-2012 (P = .049). Among overweight/obese adolescents, adjusted pre-HBP prevalence was 17.5% during 1988-2012, and 20.9% during 2007-2012 (P = .323); adjusted HBP prevalence declined significantly from 7.2% during 1988-1994 to 3.2% during 2007 2012 (P = .018). Because of population growth, estimated number of adolescents with pre-HBP or HBP increased, from 4.18 million during 1988-1994 to 5.59 million during 2007-2012. CONCLUSIONS: Between 1988 and 2012, pre-HBP prevalence was consistently higher among overweight/obese adolescent than those of normal weight, and the pattern remain unchanged. HBP prevalence declined significantly, especially among overweight/obese adolescent that are not completely explained by sociodemographic or lifestyle characteristics. PMID- 26563533 TI - Pediatric Academic Productivity: Pediatric Benchmarks for the h- and g-Indices. AB - OBJECTIVE: To describe h- and g-indices benchmarks in pediatric subspecialties and general academic pediatrics. Academic productivity is measured increasingly through bibliometrics that derive a statistical enumeration of academic output and impact. The h- and g-indices incorporate the number of publications and citations. Benchmarks for pediatrics have not been reported. STUDY DESIGN: Thirty programs were selected randomly from pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education. The h- and g-indices of department chairs were calculated. For general academic pediatrics, pediatric gastroenterology, and pediatric nephrology, a random sample of 30 programs with fellowships were selected. Within each program, an MD faculty member from each academic rank was selected randomly. Google Scholar via Harzing's Publish or Perish was used to calculate the h-index, g-index, and total manuscripts. Only peer-reviewed and English language publications were included. For Chairs, calculations from Google Scholar were compared with Scopus. RESULTS: For all specialties, the mean h- and g-indices significantly increased with academic rank (all P < .05) with the greatest h-indices among Chairs. The h- and g-indices were not statistically different between specialty groups of the same rank; however, mean rank h-indices had large SDs. The h-index calculation using different bibliographic databases only differed by +/-1. CONCLUSION: Mean h-indices increased with academic rank and were not significantly different across the pediatric specialties. Benchmarks for h- and g-indices in pediatrics are provided and may be one measure of academic productivity and impact. PMID- 26563534 TI - Socioeconomic Status and Hospitalization Costs for Children with Brain and Spinal Cord Injury. AB - OBJECTIVE: To determine if household income is associated with hospitalization costs for severe traumatic brain injury (TBI) and spinal cord injury (SCI). STUDY DESIGN: Retrospective cohort study of inpatient, nonrehabilitation hospitalizations at 43 freestanding children's hospitals for patients <19 years old with unintentional severe TBI and SCI from 2009-2012. Standardized cost of care for hospitalizations was modeled using mixed-effects methods, adjusting for age, sex, race/ethnicity, primary payer, presence of chronic medical condition, mechanism of injury, injury severity, distance from residence to hospital, and trauma center level. Main exposure was zip code level median annual household income. RESULTS: There were 1061 patients that met inclusion criteria, 833 with TBI only, 227 with SCI only, and 1 with TBI and SCI. Compared with those with the lowest-income zip codes, patients from the highest-income zip codes were more likely to be older, white (76.7% vs 50.4%), have private insurance (68.9% vs 27.9%), and live closer to the hospital (median distance 26.7 miles vs 81.2 miles). In adjusted models, there was no significant association between zip code level household income and hospitalization costs. CONCLUSIONS: Children hospitalized with unintentional, severe TBI and SCI showed no difference in standardized hospital costs relative to a patient's home zip code level median annual household income. The association between household income and hospitalization costs may vary by primary diagnosis. PMID- 26563535 TI - Point-of-Care Ultrasonography for the Diagnosis of Pediatric Soft Tissue Infection. AB - OBJECTIVES: To determine the test characteristics of point-of-care ultrasonography for the identification of a drainable abscess and to compare the test characteristics of ultrasonography with physical examination. In addition, we sought to measure the extent to which ultrasonography impacts clinical management of children with skin and soft tissue infections (SSTIs). STUDY DESIGN: We performed a prospective study of children with SSTIs evaluated in a pediatric emergency department. Treating physicians recorded their initial impression of whether a drainable abscess was present based on physical examination. Another physician, blinded to the treating physician's assessment, performed an ultrasound study and conveyed their interpretation and recommendations to the treating physician. Any management change was recorded. An abscess was defined as a lesion from which purulent fluid was expressed during a drainage procedure in the emergency department or during the 2- to 5-day follow up period. We defined a change in management as correct when the ultrasound diagnosis was discordant from physical examination and matched the ultimate lesion classification. RESULTS: Of 151 SSTIs evaluated among 148 patients, the sensitivity and specificity of point-of-care ultrasonography for the presence of abscess were 96% (95% CI 90%-99%) and 87% (74%-95%), respectively. The sensitivity and specificity of physical examination for the presence of abscess were 84% (75%-90%) and 60% (44%-73%), respectively. For every 4 ultrasound examinations performed, there was 1 correct change in management. CONCLUSIONS: Point-of-care ultrasonography demonstrates excellent test characteristics for the identification of skin abscess and has superior test characteristics compared with physical examination alone. PMID- 26563536 TI - Childhood Obesity and Delayed Gratification Behavior: A Systematic Review of Experimental Studies. AB - OBJECTIVE: To evaluate the extent of the association between instant gratification behavior and childhood obesity. STUDY DESIGN: PubMed, Scopus, EMBASE, EBSCOhost, and Cochrane databases were searched for the terms delayed gratification, children, and obesity. Studies were eligible if they included a sample of at least 100 children who were made to choose between an immediate reward and a larger one later, with the authors comparing the response in different populations and observing some relationship with obesity. A specifically designed data extraction form was used, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodologic quality of the included studies was assessed with the methodologic index for nonrandomized studies. RESULTS: Nine articles were included after we applied the inclusion and exclusion criteria. Almost all studies conducted the test in populations of preschool children and offered food and/or nonfood rewards. The studies found a clear relationship between an inability to defer gratification and overweight and obesity. The quality assessment of the publications was ranked high in 5 studies and medium in 4. CONCLUSIONS: Children with the inability to delay gratification are more likely to be overweight or obese. Observation of such trends is useful in its implications for reeducation programs. Although the methodologic quality of the eligible studies was acceptable, additional experimental controlled studies are required to associate these behaviors with other aspects. PMID- 26563537 TI - The fluoroscopy time, door to balloon time, contrast volume use and prevalence of vascular access site failure with transradial versus transfemoral approach in ST segment elevation myocardial infarction: A systematic review & meta-analysis. AB - OBJECTIVE: The authors aimed to conduct first systematic review and meta-analysis in STEMI patients evaluating vascular access site failure rate, fluoroscopy time, door to balloon time and contrast volume used with transradial vs transfemoral approach (TRA vs TFA) for PCI. METHODS: The PubMed, CINAHL, clinicaltrials.gov, Embase and CENTRAL databases were searched for randomized trials comparing TRA versus TFA. Random effect models were used to conduct this meta-analysis. RESULTS: Fourteen randomized trials comprising 3758 patients met inclusion criteria. The access site failure rate was significantly higher TRA compared to TFA (RR 3.30, CI 2.16-5.03; P=0.000). Random effect inverse variance weighted prevalence rate meta-analysis showed that access site failure rate was predicted to be 4% (95% CI 3.0-6.0%) with TRA versus 1% (95% CI 0.0-1.0 %) with TFA. Door to balloon time (Standardized mean difference [SMD] 0.30 min, 95% CI 0.23-0.37 min; P=0.000) and fluoroscopy time (Standardized mean difference 0.14 min, 95% CI 0.06-0.23 min; P=0.001) were also significantly higher in TRA. There was no difference in the amount of contrast volume used with TRA versus TFA (SMD -0.05 ml, 95% CI -0.14 to 0.04 ml; P=0.275). Statistical heterogeneity was low in cross over rate and contrast volume use, moderate in fluoroscopy time but high in the door to balloon time comparison. CONCLUSION: Operators need to consider higher cross-over rate with TRA compared to TFA in STEMI patients while attempting PCI. Fluoroscopy and door to balloon times are negligibly higher with TRA but there is no difference in terms of contrast volume use. PMID- 26563538 TI - Single and Cumulative Relations of Social Risk Factors with Children's Dental Health and Care-Utilization Within Regions of the United States. AB - OBJECTIVES: The purpose is to examine the relation of social risk factors, and the cumulative burden of social risk factors, on parent-reported dental health and dental care-seeking behavior. METHODS: National Survey of Children's Health data (2011-2012) were analyzed for US children by Title V Block Grant regions. Multivariate logistic regressions were estimated for ten social risk factors, as well as a cumulative risk index, to find any associations with poor condition of teeth, presence of dental caries, and no dental care visits. RESULTS: Almost all of the risk factors were significantly associated with poor condition of teeth and presence of dental caries for the US. Models associating no dental care visits suggested that low family income (OR 1.58), poor maternal mental health (OR 1.54), high school education or less (OR 1.34), and multi-racial/other race (OR 1.18) were significant factors for the US. Regional variation existed for those risk factors and their association with the outcomes, but income, education, and poor maternal mental health consistently played a significant role in adverse outcomes. The cumulative risk index was strongly related to poor oral health outcomes, with a weaker relationship to dental care utilization. CONCLUSIONS FOR PRACTICE: US children experiencing certain social risk factors, such as low family income, high school education or less, and poor maternal mental health, are likely to be at greater risk for poor dental health and low levels of dental-care seeking behavior. Children experiencing multiple social risks are at greater risk for poor oral outcomes than children who experience fewer social risks. An approach that involves the social determinants of health is needed to address these issues. PMID- 26563539 TI - Percutaneous renal transplant biopsy: is the safety profile adequate for short term postprocedure monitoring? PMID- 26563540 TI - Excessive TLR9 signaling contributes to the pathogenesis of spontaneous abortion through impairment of Treg cell survival by activation of Caspase 8/3. AB - BACKGROUND: The pregnant uterine microenvironment is repleted with Toll-like receptors (TLRs), however, their roles of these receptors in establishing tolerance to growing fetus are largely unknown. RESULT: Decidual TLR1, TLR3, TLR4, TLR8 and TLR9 gene expressions were significantly over-expressed in patients of spontaneous abortion compared with elective abortion with normal pregnancy. In particular, the expression of TLR4 and TLR9 mRNA was considerably higher than that of remaining TLRs. We mimic TLR9 signal with combination of its pathogenic ligand CpG ODN and antagonists ODN in a well-established abortion prone CBA/J*DBA/2 model. CpG ODN dramatically boosted fetal loss and lowered the proportion of Regulatory cells (Treg cells) in vivo. CpG ODN directly triggered the impaired survival and increased activity of Caspase 8/3 of Treg cells in vitro. These effects were blocked by antagonist ODN. CONCLUSION: Excessive TLR9 signaling contributed to maternal-fetal tolerance disruption via an effect on Treg cell survival by activation of Caspase 8/3. PMID- 26563541 TI - CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients. AB - The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients. A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered a positive response to treatment. A total of 116 patients (78 responders and 38 non-responders) were genotyped for the CDKAL1 rs6908425, rs4712523, rs111739077, and rs77152992 (p.P409L) single nucleotide polymorphisms. Allele and genotype frequencies differed between the two response groups, with the highest difference for the rs6908425: CC homozygotes were significantly more common among responders (72% vs. 45%; p=0.005; OR=3.14, 95%CI=1.40-7.05). In conclusion, our data suggested that CDKAL1 gene variants have a significant effect on the response to anti-TNF therapies among Psor patients. If confirmed on other large cohorts of patients, the genotyping of these variants might help to predict the biological response. PMID- 26563542 TI - Reducing microplastics from facial exfoliating cleansers in wastewater through treatment versus consumer product decisions. AB - Microplastics (<5mm) have been discovered in fresh and saltwater ecosystems, sediments, and wastewater effluent around the world. Their ability to persist and accumulate up food chains should be a concern as research is still experimenting with techniques to assess their long-term effects on the environment. I sought to characterize the microbeads found in facial exfoliating cleansers so as to better understand how to reduce this source of pollution through consumer use and wastewater treatment solutions. By sampling products from national-grossing cosmetic personal care brands, I was able to gather information on the size, color, volume, mass, and concentration of polyethylene beads in the cleansers. From that data, I modeled onto a consumer survey the estimated volume of microplastics entering a wastewater stream. Through inquiry, I learned the practices of two local wastewater treatment facilities. My findings show that consumer decisions and treatment protocols both play crucial parts in minimizing microplastic pollution. PMID- 26563543 TI - Cumulative pressures and low protection: a concerning blend for Mediterranean MPAs. AB - This study classifies Mediterranean marine protected areas (MPAs) according to the combined result of pressure level and protection. Six major marine environment pressures were considered: pressures from fish farms, fishing, marine litter, pressures from marinas, pollution from maritime transport, and climate change. MPA protection was assessed through legal protection and management effort. Most MPA area in the Mediterranean is under relatively high pressure level and afforded low protection. Inshore areas show higher pressure levels. Five marine ecoregions, nine countries and nineteen MPA designation categories have over 50% of their MPA area under major concern. The mean number of cumulative pressures occurring in priority MPAs ranges between three and four, although the mean combined intensity of those pressures is low. However, these figures are most likely underestimated, especially for the southern Mediterranean. The most concerning pressures to MPAs regarding extent and intensity were: climate change, fishing and pollution from maritime transport. PMID- 26563544 TI - Distribution and source apportionment of polycyclic aromatic hydrocarbons in surface sediments from Zhoushan Archipelago and Xiangshan Harbor, East China Sea. AB - Zhoushan Archipelago and the adjacent Xiangshan Harbor are important commercial, tourism, fishing, and mariculture areas. Considering the concern on the effects of anthropogenic activities on the environment, the level and source apportionment of polycyclic aromatic hydrocarbons (PAHs) in surface sediments were investigated. The sum of 16 PAH (?16 PAH) concentrations in the Zhoushan Archipelago ranged from 3.67 to 31.30 ng g(-1) d.w., with a mean of 15.01 +/- 1.21 ng g(-1) d.w., and that in Xiangshan Harbor varied from 11.58 to 481.44 ng g(-1) d.w., with a mean of 62.52 +/- 32.85 ng g(-1) d.w. Diagnostic ratios and factor analysis were performed to identify PAH sources. Results show that PAHs have mixed origins (i.e., traffic-related sources, coal combustion, petrogenic sources, and biomass burning), with pyrolytic-related pollution as the dominant source. This study provided a baseline to promote environmental protection and pollution episode monitoring in the East China Sea. PMID- 26563545 TI - Benthic foraminifera as indicators of habitat change in anthropogenically impacted coastal wetlands of the Ebro Delta (NE Iberian Peninsula). AB - Present-day habitats of the Ebro Delta, NE Iberian Peninsula, have been ecologically altered as a consequence of intensive human impacts in the last two centuries (especially rice farming). Benthic foraminiferal palaeoassemblages and sediment characteristics of five short cores were used to reconstruct past wetland habitats, through application of multivariate DCA and CONISS techniques, and dissimilarity coefficients (SCD). The timing of environmental changes was compared to known natural and anthropogenic events in order to identify their possible relationships. In deltaic wetlands under altered hydrological conditions, we found a decrease in species diversity and calcareous-dominated assemblages, and a significant positive correlation between microfaunal changes and organic matter content. Modern analogues supported palaeoenvironmental interpretation of the recent evolution of the Delta wetlands. This research provides the first recent reconstruction of change in the Ebro Delta wetlands, and also illustrates the importance of benthic foraminifera for biomonitoring present and future conditions in Mediterranean deltas. PMID- 26563546 TI - Developmental toxicity of three hexabromocyclododecane diastereoisomers in embryos of the marine medaka Oryzias melastigma. AB - The composition of major hexabromocyclododecane (HBCD) diastereoisomers, i.e. alpha-, beta-, and gamma-HBCDs, in marine biota is different from that of the commercially available form (technical HBCD), which is used extensively for toxicological studies. To properly evaluate the impact of HBCDs, the embryos of Oryzias melastigma were used to examine the developmental toxicity of the individual diastereoisomers. Results showed that HBCD diastereoisomers at the environmentally realistic concentrations in the embryos induced malformation rate and heartbeat, and caused the appearance of apoptotic heart. In addition, alpha-, beta-, and gamma-HBCDs had similar potency to stimulate the generation of reactive oxygen species, consequently leading to apoptosis in O. melastigma embryos. The order of the developmental toxicity of alpha-, beta-, and gamma HBCDs in O. melastigma embryos was different from that in zebrafish embryos studied previously, which highlighted the importance of using species from both fresh and salt water for toxicity assessment. PMID- 26563547 TI - Prickly business: abundance of sea urchins on breakwaters and coral reefs in Dubai. AB - Echinometra mathaei is a common echinoid on tropical reefs and where abundant plays an important role in the control of algal communities. Despite high prevalence of E. mathaei on southern Persian/Arabian Gulf reefs, their abundance and distribution is poorly known. Spatial and temporal patterns in population abundance were examined at 12 sites between breakwater and natural reef habitats in Dubai (UAE) every 3 months from 2008 to 2010. Within the breakwater habitat, densities were greatest at shallow wave-exposed sites, and reduced with both decreasing wave-exposure and increasing depth. Interestingly, E. mathaei were significantly more abundant on exposed breakwaters than natural reef sites, presumably due to differences in habitat structure and benthic cover. Population abundances differed seasonally, with peak abundances during summer (July September) and lower abundances in winter (December-February). Seasonal fluctuations are likely the result of peak annual recruitment pulses coupled with increased fish predation from summer to winter. PMID- 26563548 TI - Assessment of metal contamination in coastal sediments, seawaters and bivalves of the Mediterranean Sea coast, Egypt. AB - In order to assess metal contamination on the Mediterranean coast of Egypt, 45 sediment samples, seawaters and bivalve specimens were collected from Rosetta coastal area for Mg, Al, K, Fe, Sr, Zn, Pb, Mn, As, Ce, Ni, Cr and Zr analyses by Inductively Coupled Plasma-Mass Spectrometer. The Enrichment Factor (EF), the Geoaccumulation Index (Igeo) and the Contamination Factor (CF) indicated that the coastal sediments of Rosetta area were severely enriched, strongly polluted with As, Pb and very highly contaminated with As, Pb, Ni, Ce, mostly as a result of anthropogenic inputs. Comparison with other samples from the Arabian Gulf, Red Sea and abroad coasts suggested that the studied samples have higher concentrations of Fe, Pb, As, Zn and Ni. The natural sources of heavy metals in the study area are attributed to weathering and decomposition of mountain ranges of the Sudan and Ethiopia, while the anthropogenic ones are the metals produced from industrial, sewage, irrigation and urban runoff. PMID- 26563549 TI - Characterization of microbial compositions in a thermophilic chemostat of mixed culture fermentation. AB - The microbial community compositions of a chemostat enriched in a thermophilic (55 degrees C) mixed culture fermentation (MCF) for hydrogen production under different operational conditions were revealed in this work by integrating denaturing gradient gel electrophoresis (DGGE), Illumina Miseq high-throughput sequencing, and 16S rRNA clone library sequencing. The results showed that the community structure of the enriched cultures was relatively simple. Clones close to the genera of Thermoanaerobacter and/or Bacillus mainly dominated the bacteria. And homoacetogens and archaea were washed out and not detected even by Illumina Miseq high-throughput sequencing which supported the benefit for hydrogen production. On the other hand, the results revealed that the metabolic shift was clearly associated with the change of dominated bacterial groups. The effects of hydrogen partial pressure (PH2) and pH from 4.0 to 5.5 on the microbial compositions were not notable and Thermoanaerobacter was dominant, thus, the metabolites were also not changed. While Bacillus, Thermoanaerobacter and Propionispora hippei dominated the bacteria communities at neutral pH, or Bacillus and Thermoanaerobacter dominated at high influent glucose concentrations, consequently the main metabolites shifted to acetate, ethanol, propionate, or lactate. Thereby, the effect of microbial composition on the metabolite distribution and shift shall be considered when modeling thermophilic MCF in the future. PMID- 26563550 TI - Silica fertilization and nano-MnO2 amendment on bacterial community composition in high arsenic paddy soils. AB - Silica fertilization and nano-MnO2 amendment are reported as useful approaches in lowering the accumulation of arsenic in rice grains, but the effects of silica fertilization or nano-MnO2 amendment on microbial community in the paddy soils containing high concentration of arsenic are still unknown. In order to elucidate this question, the structures and composition of microbial community in the paddy soils, in response to silica fertilization and nano-MnO2 amendment, were investigated using pyrosequencing technique. The results indicated that Proteobacteria, Chloroflexi, and Acidobacteria were the main dominating phyla in these paddy soils. A decrease in the relative abundance of Chloroflexi and Cyanobacteria, but an increase in the relative abundance of Acidobacteria was observed after silica fertilization and nano-MnO2 amendment. The changes of Acidobacteria, Chloroflexi, and Cyanobacteria were strongly correlated with pH and the concentration of bioavailable arsenic in the paddy soils. The alpha diversity of bacteria in the paddy soils increased in response to silica fertilization at low amendment level, but decreased under silica or nano-MnO2 amendment at high amendment level. Results of beta-diversity analysis indicated that the microbial communities in the control treatment shared more similarity with that of those received low level of nano-MnO2 amendment, and the two silica fertilization treatments also shared more similarity with each other. PMID- 26563551 TI - Antibiotic sulfanilamide biodegradation by acclimated microbial populations. AB - Sulfonamide antibiotics are commonly detected in the environment. Microbial degradation can play an important role in the dissipation of sulfonamide antibiotics. However, many aspects regarding the influential factor and biodegradation pathway remain essentially unclear. Moreover, phylogenetic information on the sulfonamide-degrading microbial community is still very limited. The present study investigated the biodegradation of sulfonamide antibiotic sulfanilamide by acclimated mixed culture and its influential factors, and the sulfanilamide-degrading microbial community. At the initial sulfanilamide concentration of 100 MUg/L, nearly half of the antibiotic could be removed by acclimated microbial populations after 1 week of incubation, and an average removal rate of 78.3 % could be achieved in 4 weeks. p-Phenylenediamine, benzene sulfonamide, and hydroxylamine benzene sulfonamide were identified as the potential intermediates. Sulfanilamide biodegradation could be enhanced by a temperature rise and the presence of external carbon or nitrogen sources. The richness, diversity, and structure of the bacterial community showed a remarkable change with sulfanilamide biodegradation. Firmicutes and Bacteroidetes (mainly represented by classes Bacilli and Flavobacteriia) dominated the sulfanilamide degrading bacterial community. PMID- 26563552 TI - Identification and characterization of novel small molecule inhibitors of the acetyltransferase activity of Escherichia coli N-acetylglucosamine-1-phosphate uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). AB - This study aims at identifying novel chemical scaffolds as inhibitors specific to the acetyltransferase domain of a bifunctional enzyme, Escherichia coli GlmU, involved in the cell wall biosynthesis of Gram-negative organisms. A two-pronged approach was used to screen a 50,000 small-molecule library. Using the first approach, the library was in silico screened by docking the library against acetyltransferase domain of E. coli GlmU studies. In the second approach, complete library was screened against Escherichia coli ATCC 25922 to identify the whole cell active compounds. Active compounds from both the screens were screened in a colorimetric absorbance-based assay to identify inhibitors of acetyltransferase domain of E. coli GlmU which resulted in the identification of 1 inhibitor out of 56 hits identified by in silico screening and 4 inhibitors out of 35 whole cell active compounds on Gram-negative bacteria with the most potent inhibitor showing IC50 of 1.40 +/- 0.69 MUM. Mode of inhibition studies revealed these inhibitors to be competitive with AcCoA and uncompetitive with GlcN-1-P. These selected inhibitors were also tested for their antibacterial and cytotoxic activities. Compounds 5175178 and 5215319 exhibited antibacterial activity that co-related with GlmU inhibition. These compounds, therefore, represent novel chemical scaffolds targeting acetyltransferase activity of E. coli GlmU. PMID- 26563553 TI - Anti-NMDA receptor encephalitis: clinical characteristics, predictors of outcome and the knowledge gap in southwest China. AB - BACKGROUND AND PURPOSE: The aim was to analyse the clinical profiles and outcomes of patients with anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in China. METHODS: A retrospective study of anti-NMDAR encephalitis in China was performed between June 2011 and June 2014. The clinical characteristics and predictors of poor outcome were determined. RESULTS: A total of 51 patients with a definitive diagnosis of anti-NMDAR encephalitis were included in this study. Four of them were surgically confirmed to have a neoplasm. Thirty-two patients, amongst whom 24 were female, presented with psychiatric disorder as the initial symptom, whereas 14 patients, of whom nine were male, presented with seizure as the initial symptom (P = 0.011). Twenty-nine patients (56.86%) were initially misdiagnosed with psychosis, viral encephalitis or other diseases, and 58.8% of the patients experienced at least one type of complication. It typically took 3 weeks before these patients were admitted to our hospital and another 2 weeks before the correct diagnosis was made. Forty-one patients (80%) reached a good outcome; 10 patients (20%) had a poor outcome. Older age, extended hospital stay, memory deficits, decreased consciousness, central hypoventilation, complications and abnormal cerebrospinal fluid results were associated with poor outcome (P < 0.05). CONCLUSIONS: Female patients more frequently initially present with psychiatric disorder but male patients more frequently initially present with seizure. Patients with anti-NMDAR encephalitis in China have a lower incidence of neoplasm. Nevertheless, this study reveals several challenges in treating anti NMDAR encephalitis in China that may contribute to poor outcome. PMID- 26563554 TI - LiNi(0.5)Mn(1.5)O4 high-voltage cathode coated with Li4Ti5O12: a hard X-ray photoelectron spectroscopy (HAXPES) study. AB - A Li4Ti5O12 (LTO) film was coated as buffer layer onto a LiNi0.5Mn1.5O4 (LNMO) high-voltage cathode, and after cycling of the cathode in a battery electrolyte, the LTO film was investigated by means of synchrotron radiation based hard X-ray photoelectron spectroscopy (HAXPES). By tuning the photon energy between 2 keV and 6 keV, we obtained non-destructive depth profiles of the coating material with probing depths ranging from 6 nm to 20 nm. The coating was found to be covered by a few nanometers thin surface layer resulting from electrolyte decomposition. This layer consisted predominantly of organic polymers as well as metal fluorides and fluorophosphates. A positive influence of the Li4Ti5O12 coating with regard to the size and stability of the surface layer was found. The coating itself consisted of a uniform mixture of Li(I), Ti(IV), Ni(II) and Mn(IV) oxides that most likely adopted a spinel structure by forming a solid solution of the two spinels LiNi0.5Mn1.5O4 and Li4Ti5O12 with Li, Mn, Ni and Ti cations mixing on the spinel octahedral sites. The diffusion of Ni and Mn ions into the Li4Ti5O12 lattice occurred during the heat treatment when preparing the cathode. The doping of Li4Ti5O12 with the open d-shell ions Ni(2+) (d(8)) and Mn(4+) (d(3)) should increase the electronic conductivity of the coating significantly, as was found in previous studies. The complex signal structure of the Ti 2p, Ni 2p and Mn 2p core levels provides insight into the chemical nature of the transition metal ions. PMID- 26563555 TI - Efficacy of Bacillus subtilis V26 as a biological control agent against Rhizoctonia solani on potato. AB - The aim of this study is to evaluate the efficacy of the strain Bacillus subtilis V26, a local isolate from the Tunisian soil, to control potato black scurf caused by Rhizoctonia solani. The in vitro antifungal activity of V26 significantly inhibited R. solani growth compared to the untreated control. Microscopic observations revealed that V26 caused considerable morphological deformations of the fungal hyphae such as vacuolation, protoplast leakage and mycelia crack. The most effective control was achieved when strain V26 was applied 24h prior to inoculation (protective activity) in potato slices. The antagonistic bacterium V26 induced significant suppression of root canker and black scurf tuber colonization compared to untreated controls with a decrease in incidence disease of 63% and 81%, respectively, and promoted plant growth under greenhouse conditions on potato plants. Therefore, B. subtilis V26 has a great potential to be commercialized as a biocontrol agent against R. solani on potato crops. PMID- 26563556 TI - Stochastic monotony signature and biomedical applications. AB - We introduce a new concept, the stochastic monotony signature of a function, made of the sequence of the signs that indicate if the function is increasing or constant (sign +), or decreasing (sign -). If the function results from the averaging of successive observations with errors, the monotony sign is a random binary variable, whose density is studied under two hypotheses for the distribution of errors: uniform and Gaussian. Then, we describe a simple statistical test allowing the comparison between the monotony signatures of two functions (e.g., one observed and the other as reference) and we apply the test to four biomedical examples, coming from genetics, psychology, gerontology, and morphogenesis. PMID- 26563557 TI - Spawning segregation and philopatry are major prezygotic barriers in sympatric cryptic Mugil cephalus species. AB - The flathead mullet, Mugil cephalus, is a commercially vital fish in fisheries and aquaculture worldwide. Genetic analyses have recently revealed three cryptic species of M. cephalus in the Northwest Pacific. These species are sympatric in Taiwanese waters and specific reproductive behaviors have been suggested to be a major prezygotic barrier. Species composition was evaluated in samples of M. cephalus at different growth stages collected from various habitats (offshore spawning ground, estuarine nursery and feeding areas) over several months or years. The gonadosomatic index of adults and the body length of juveniles were recorded to determine the reproductive season and recruitment periods in estuaries. The results revealed partially temporal spawning isolation between species pairs, spatial segregation on specific spawning grounds and strong philopatry preclude hybridization. Thus, the results imply that traditional fisheries of mature fish in the Taiwan Strait target only one species, whereas aquaculture in Taiwan contain juveniles of all three species collected in estuaries. The ecological niche and demography of these species must be investigated further to estimate the impact of juvenile sources on aquaculture. PMID- 26563558 TI - Surface-enhanced Raman scattering on silvered porous alumina templates: role of multipolar surface plasmon resonant modes. AB - Nanostructured silver films with different thicknesses were prepared by vapor deposition onto the surface of the anodic aluminum oxide (AAO) template to be used as surface-enhanced Raman scattering (SERS) active substrates. Both the peak position of the surface plasmon resonance (SPR) band and SERS enhancement of silvered AAO samples displayed non-monotonous dependence on Ag layer thickness. Using 441.6 nm excitation and a water-soluble cationic porphyrin, Cu(ii) tetrakis(4-N-methylpyridyl) (CuTMPyP4), as a SERS-reporting analyte, two maxima of the SERS enhancement were obtained for Ag layers of 15 and 120 nm thickness. Thickness dependencies have been analyzed taking into account the type of SPR modes identified by means of quasicrystalline approximation (QCA) of statistical theory of multiple scattering of waves and multi-Lorentzian deconvolution. The analysis revealed that SERS enhancement is related to the absolute magnitude of the distance between excitation wavelength and spectral position of collective SPR mode. It was shown that matching of excitation wavelength and the most intensive SPR modes with non-radiative decay, generated mainly by coherent interaction of higher-order plasmon resonant modes (quadrupole and octupole), plays a dominate role in SERS performance. Besides, it has been observed that more intense SERS signal can be obtained when the analyte deposited on the Ag/AAO substrate was excited through the AAO template rather than from the silvered side. Our results demonstrate that appropriate excitation geometry and fine tuning of the optical properties of the Ag/AAO substrate by adjusting the thickness of the Ag layer with respect to particular excitation wavelength can contribute to more effective SERS enhancement. PMID- 26563559 TI - Myxoinflammatory fibroblastic sarcoma: spectrum of disease and imaging presentation. AB - OBJECTIVES: To describe the imaging findings of a series of myxoinflammatory fibroblastic sarcomas (MFSs) from our institution, including a case of dedifferentiated MFS and two cases with areas of high-grade tumor, in addition to typical cases of low-grade tumor. To correlate the imaging findings with the pathologic features of these tumors. SUBJECTS AND METHODS: IRB approval was obtained. Retrospective search of the pathology database at our institution from 2000 to 2015 identified seven cases of MFS with available imaging. Imaging, pathology, and clinical data were reviewed. RESULTS: Unlike the majority of well differentiated tumors in our series (four cases), one tumor showed dedifferentiation and two cases had areas of high-grade tumor. The dedifferentiated tumor showed peripheral post-contrast enhancement. One case with a substantial high-grade component showed osseous destruction and peripheral enhancement in the high-grade area, while the low-grade component enhanced diffusely. The second case had a small high-grade area and showed diffuse enhancement. All three of these cases had non-acral locations and lacked association with a tendon. The four cases of low-grade MFS demonstrated diffuse enhancement, were located in the distal extremities, and were associated with a tendon. CONCLUSION: The imaging findings of dedifferentiated and high-grade MFS differ from the more typical low-grade tumors in that they have nonenhancing areas, a non-acral location, lack association with a tendon, and may involve bone. The radiologist should be aware that MFS represents a spectrum that includes low-grade tumors, tumors with high-grade areas, and tumors with dedifferentiation and that this spectrum presents with differing imaging features. PMID- 26563560 TI - Cone-Beam CT in diagnosis of scaphoid fractures. AB - OBJECTIVE: This prospective study investigated the sensitivity of cone beam computed tomography (CBCT), a low dose technique recently made available for extremity examinations, in detecting scaphoid fractures. Magnetic resonance imaging (MRI) was used as gold standard for scaphoid fractures. MATERIALS AND METHODS: A total of 95 patients with a clinically suspected scaphoid fracture were examined with radiography and CBCT in the acute setting. A negative CBCT exam was followed by an MRI within 2 weeks. When a scaphoid fracture was detected on MRI a new CBCT was performed. RESULTS: Radiography depicted seven scaphoid fractures, all of which were also seen with CBCT. CBCT detected another four scaphoid fractures. With MRI another five scaphoid fractures were identified that were not seen with radiography or with CBCT. These were also not visible on the reexamination CBCT. Sensitivity for radiography was 44, 95 % confidence interval 21-69 %, and for CBCT 69 %, 95 % confidence interval 41-88 % (p = 0.12). Several non-scaphoid fractures in the carpal region were identified, radiography and CBCT depicted 7 and 34, respectively (p < 0.0001). CONCLUSION: CBCT is a superior alternative to radiography, entailing more accurate diagnoses of carpal region fractures, and thereby requiring fewer follow-up MRI examinations. However, CBCT cannot be used to exclude scaphoid fractures, since MRI identified additional occult scaphoid fractures. PMID- 26563561 TI - Short- and long-term reproducibility of marrow adipose tissue quantification by 1H-MR spectroscopy. AB - OBJECTIVE: To assess short- and long-term reproducibility of marrow adipose tissue (MAT) quantification by 1H-MR spectroscopy. MATERIALS AND METHODS: Our study was IRB-approved and HIPAA compliant. Written informed consent was obtained. We studied 20 overweight/obese but otherwise healthy subjects (12 female, 8 male) with a mean age of 37 +/- 6 years. All subjects underwent proton magnetic resonance spectroscopy (1H-MRS) of the fourth lumbar vertebral body using a single-voxel point-resolved spatially localized spectroscopy sequence without water suppression at 3 T. Measurements were repeated after 6 weeks and 6 months using identical scanning protocols. The following clinical parameters were collected, weight, BMI, exercise status, and trabecular bone mineral density (BMD), by quantitative computed tomography. Short- (baseline, 6 weeks) and long term (baseline, 6 months) reproducibility of MAT was assessed by the coefficient of variance (CV), standard deviation (SD), and interclass correlation coefficients (ICCs). Short- and long-term changes in clinical parameters were assessed by paired t-test. RESULTS: For short-term reproducibility between baseline and 6-week scans, the CV was 9.9 %, SD was 0.08, and ICC was 0.97 (95 % CI 0.94-099). For long-term reproducibility between baseline and 6-month scans, the CV was 12.0 %, SD was 0.10, and ICC was 0.95 (95 % CI 0.88 to 0.98). There was no significant short- or long-term change in clinical parameters (weight, BMI, exercise status, BMD) (p > 0.2). CONCLUSION: 1H-MRS is a reproducible method for short- and long-term quantification of MAT. Our results can guide sample size calculations for interventional and longitudinal studies. PMID- 26563562 TI - Linking medical faculty stress/burnout to willingness to implement medical school curriculum change: a preliminary investigation. AB - RATIONALE, AIMS AND OBJECTIVES: Balancing administrative demands from the medical school while providing patient support and seeking academic advancement can cause personal hardship that ranges from high stress to clinically recognizable conditions such as burnout. Regarding the importance of clinical faculties' burnout and its effects on different aspects of their professional career, this study was conducted and aimed to evaluate the relationship between willingness to change teaching approaches as characterized by a modified stage-of-change model and measures of stress and burnout. METHODS: This descriptive analytic study was conducted on 143 clinical faculty members of Tehran University of Medical Sciences in Iran. Participants were asked to complete three questionnaires: a modified stages of change questionnaire the Maslach Burnout Inventory and the General Health Questionnaire. Data were analysed by SPSS: 16 using non-parametric statistical tests such as multiple regression and ICC (intra-class coefficient) and Spearman correlation coefficient test. RESULT: A significant relationship was found between faculty members' readiness to change teaching approaches and the subscales of occupational burnout. Specifically, participants with low occupational burnout were more likely to be in the action stage, while those with high burnout were in the attitude or intention stage, which could be understood as not being ready to implement change. There was no significant correlation between general health scores and stage of change. CONCLUSIONS: We found it feasible to measure stages of change as well as stress/burnout in academic doctors. Occupational burnout directly reduces the readiness to change. To have successful academic reform in medical schools, it therefore would be beneficial to assess and manage occupational burnout among clinical faculty members. PMID- 26563563 TI - Understanding the fundamentals of redox mediators in Li-O2 batteries: a case study on nitroxides. AB - The development of aprotic lithium-oxygen (Li-O2) batteries suffers from high charging overvoltages. Dissolved redox mediators, like nitroxides, providing increased energy efficiency and longer lifetime are promising tools to overcome this challenge. Since this auspicious concept is still in its infancy, the underlying chemical reactions as well as the impact of the different (electro)chemical parameters are poorly understood. Herein, we derive an electrochemical model for the charging reactions, which is validated by potentiostatic measurements. The model elucidates the impact of the major factors including basic cell parameters and the chemical properties of the redox mediator. The model is applied to the promising class of nitroxides, which is systematically investigated by using derivatives of TEMPO (2,2,6,6-tetramethyl-1 piperidinyloxy), AZADO (2-azaadamantane-N-oxyl), and an azaphenalene based nitroxide. The nitroxides are electrochemically characterized by cyclic voltammetry and their performance as redox mediators is studied in Li-O2 batteries with an ether-based electrolyte. Based on the presented model, the charging profiles of the different nitroxide redox mediators are correlated with their molecular structures. PMID- 26563564 TI - Evaluating factors associated with implementing evidence-based practice in nursing. AB - RATIONALE, AIMS AND OBJECTIVES: Evidence-based practice (EBP) has emerged as an innovation for quality improvement in health care. Nurses have important role in implementing EBP but they face many challenges in this context. Evaluation of factors influencing implementation of EBP seems necessary. The aims of this study were to examine nurses' attitude towards EBP, their self-efficacy and training needs, as well as supporting factors and barriers for implementing EBP. METHODS: A cross-sectional study was conducted on 182 nurses from four teaching hospitals in Kerman, Iran. Data were collected using a questionnaire consisting of two main sections; a section to collect socio-demographic information of participants and a section collecting information on five topics (staff's attitude, self-efficacy skills of EBP, supporting factors, barriers and training needs for implementing EBP). RESULTS: The majority (87.4%) of the nurses had not attended any formal training on EBP and 60% of them were not familiar with the concept of EBP. Nurses' attitude towards EBP was unfavourable (2.57 +/- 0.99) and their self efficacy skills of EBP were poor (2.93 +/- 1.06). The most important supporting factor was mentoring by nurses who have adequate EBP experience (3.65 +/- 1.17) and the biggest barrier was difficulty judging the quality of research papers and reports (2.46 +/- 0.95). There was a moderate demand for training in all areas of EBP (3.62 +/- 1.12). CONCLUSIONS: Nursing care needs to move towards quality improvement using EBP. It is necessary to equip nurses with knowledge and skills required for EBP. Managers should design an appropriate strategic plan by considering supporting factors and barriers for integrating EBP into clinical setting. PMID- 26563566 TI - Deviation of polarity from linearity in liquid mixtures containing an ionic liquid. AB - The physico-chemical properties of liquid mixtures, in general, exhibit deviations from linear behaviour with respect to their composition, arising out of different types of cross-intermolecular interactions (both specific and non specific). These specific and non-specific interactions can however be monitored to obtain the linear mixing in liquid mixtures using the pseudo-solvent methodology in such a manner that the interactions causing deviations from linearity are cancelled out and mixtures display linear behaviour. PMID- 26563565 TI - Crystal structure of an antigenic outer-membrane protein from Salmonella Typhi suggests a potential antigenic loop and an efflux mechanism. AB - ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOT(TM)). The crystal structure of ST50 at a resolution of 2.98 A reveals a trimer that forms an alpha-helical tunnel and a beta-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-beta-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen. PMID- 26563567 TI - Phosphatidylinositol 3,5-Bisphosphate-Rich Membrane Domains in Endosomes and Lysosomes. AB - Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 ) has critical functions in endosomes and lysosomes. We developed a method to define nanoscale distribution of PtdIns(3,5)P2 using freeze-fracture electron microscopy. GST-ATG18-4*FLAG was used to label PtdIns(3,5)P2 and its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P) was blocked by an excess of the p40(phox) PX domain. In yeast exposed to hyperosmotic stress, PtdIns(3,5)P2 was concentrated in intramembrane particle (IMP)-deficient domains in the vacuolar membrane, which made close contact with adjacent membranes. The IMP-deficient domain was also enriched with PtdIns(3)P, but was deficient in Vph1p, a liquid-disordered domain marker. In yeast lacking either PtdIns(3,5)P2 or its effector, Atg18p, the IMP-deficient, PtdIns(3)P-rich membranes were folded tightly to make abnormal tubular structures, thus showing where the vacuolar fragmentation process is arrested when PtdIns(3,5)P2 metabolism is defective. In HeLa cells, PtdIns(3,5)P2 was significantly enriched in the vesicular domain of RAB5- and RAB7-positive endosome/lysosomes of the tubulo-vesicular morphology. This biased distribution of PtdIns(3,5)P2 was also observed using fluorescence microscopy, which further showed enrichment of a retromer component, VPS35, in the tubular domain. This is the first report to show segregation of PtdIns(3,5)P2 -rich and -deficient domains in endosome/lysosomes, which should be important for endosome/lysosome functionality. PMID- 26563569 TI - Rational Improvement of Molar Absorptivity Guided by Oscillator Strength: A Case Study with Furoindolizine-Based Core Skeleton. AB - The rational improvement of photophysical properties can be highly valuable for the discovery of novel organic fluorophores. Using our new design strategy guided by the oscillator strength, we developed a series of full-color-tunable furoindolizine analogs with improved molar absorptivity through the fusion of a furan ring into the indolizine-based Seoul fluorophore. The excellent correlation between the computable values (oscillator strength and theoretical S0 -S1 energy gap) and photophysical properties (molar absorptivity and emission wavelength) confirmed the effectualness of our design strategy. PMID- 26563568 TI - Synergistic Activation of Latent HIV-1 Expression by Novel Histone Deacetylase Inhibitors and Bryostatin-1. AB - Viral reactivation from latently infected cells has become a promising therapeutic approach to eradicate HIV. Due to the complexity of the viral latency, combinations of efficient and available drugs targeting different pathways of latency are needed. In this work, we evaluated the effect of various combinations of bryostatin-1 (BRY) and novel histone deacetylase inhibitors (HDACIs) on HIV-reactivation and on cellular phenotype. The lymphocyte (J89GFP) or monocyte/macrophage (THP89GFP) latently infected cell lines were treated with BRY, panobinostat (PNB) and romidepsin (RMD) either alone or in combination. Thus, the effect on the viral reactivation was evaluated. We calculated the combination index for each drug combination; the BRY/HDACIs showed a synergistic HIV-reactivation profile in the majority of the combinations tested, whereas non synergistic effects were observed when PNB was mixed with RMD. Indeed, the 75% effective concentrations of BRY, PNB and RMD were reduced in these combinations. Moreover, primary CD4 T cells treated with such drug combinations presented similar activation and proliferation profiles in comparison with single drug treated cells. Summing up, combinations between BRY, PNB and/or RMD presented a synergistic profile by inducing virus expression in HIV-latently infected cells, rendering these combinations an attractive novel and safe option for future clinical trials. PMID- 26563571 TI - Chemical dynamics simulations of energy transfer, surface-induced dissociation, soft-landing, and reactive-landing in collisions of protonated peptide ions with organic surfaces. AB - There are two components to the review presented here regarding simulations of collisions of protonated peptide ions peptide-H(+) with organic surfaces. One is a detailed description of the classical trajectory chemical dynamics simulation methodology. Different simulation approaches are used, and identified as MM, QM + MM, and QM/MM dependent on the potential energy surface used to represent the peptide-H(+) + surface collision. The second are representative examples of the information that may be obtained from the simulations regarding energy transfer and peptide-H(+) surface-induced dissociation, soft-landing, and reactive-landing for the peptide-H(+) + surface collisions. Good agreement with experiment is obtained for each of these four collision properties. The simulations provide atomistic interpretations of the peptide-H(+) + surface collision dynamics. PMID- 26563570 TI - Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations. AB - Pericytes regulate vessel stability and pericyte dysfunction contributes to retinopathies, stroke, and cancer. Here we define Notch as a key regulator of pericyte function during angiogenesis. In Notch1(+/-); Notch3(-/-) mice, combined deficiency of Notch1 and Notch3 altered pericyte interaction with the endothelium and reduced pericyte coverage of the retinal vasculature. Notch1 and Notch3 were shown to cooperate to promote proper vascular basement membrane formation and contribute to endothelial cell quiescence. Accordingly, loss of pericyte function due to Notch deficiency exacerbates endothelial cell activation caused by Notch1 haploinsufficiency. Mice mutant for Notch1 and Notch3 develop arteriovenous malformations and display hallmarks of the ischemic stroke disease CADASIL. Thus, Notch deficiency compromises pericyte function and contributes to vascular pathologies. PMID- 26563572 TI - Selective Inhibition of the Immunoproteasome by Structure-Based Targeting of a Non-catalytic Cysteine. AB - Clinically applied proteasome inhibitors induce cell death by concomitant blockage of constitutive and immunoproteasomes. In contrast, selective immunoproteasome inhibition is less cytotoxic and has the potential to modulate chronic inflammation and autoimmune diseases. In this study, we rationally designed decarboxylated peptides that covalently target a non-catalytic cysteine of the immunoproteasome subunit beta5i with alpha-chloroacetamide-containing sidechains. The enhanced isoform specificity decreased cytotoxic effects and the compound suppressed the production of inflammatory cytokines. Structure-based optimization led to over 150-fold selectivity for subunit beta5i over beta5c. This new compound class provides a promising starting point for the development of selective immunoproteasome inhibitors as potential anti-inflammatory agents. PMID- 26563573 TI - Microstructures and growth mechanisms of GaN films epitaxially grown on AlN/Si hetero-structures by pulsed laser deposition at different temperatures. AB - 2 inch-diameter GaN films with homogeneous thickness distribution have been grown on AlN/Si(111) hetero-structures by pulsed laser deposition (PLD) with laser rastering technique. The surface morphology, crystalline quality, and interfacial property of as-grown GaN films are characterized in detail. By optimizing the laser rastering program, the ~300 nm-thick GaN films grown at 750 degrees C show a root-mean-square (RMS) thickness inhomogeneity of 3.0%, very smooth surface with a RMS surface roughness of 3.0 nm, full-width at half-maximums (FWHMs) for GaN(0002) and GaN(102) X-ray rocking curves of 0.7 degrees and 0.8 degrees , respectively, and sharp and abrupt AlN/GaN hetero-interfaces. With the increase in the growth temperature from 550 to 850 degrees C, the surface morphology, crystalline quality, and interfacial property of as-grown ~300 nm-thick GaN films are gradually improved at first and then decreased. Based on the characterizations, the corresponding growth mechanisms of GaN films grown on AlN/Si hetero-structures by PLD with various growth temperatures are hence proposed. This work would be beneficial to understanding the further insight of the GaN films grown on Si(111) substrates by PLD for the application of GaN-based devices. PMID- 26563574 TI - Bioinspired polymer vesicles and membranes for biological and medical applications. AB - Biological membranes play an essential role in living organisms by providing stable and functional compartments, preserving cell architecture, whilst supporting signalling and selective transport that are mediated by a variety of proteins embedded in the membrane. However, mimicking cell membranes - to be applied in artificial systems - is very challenging because of the vast complexity of biological structures. In this respect a highly promising strategy to designing multifunctional hybrid materials/systems is to combine biological molecules with polymer membranes or to design membranes with intrinsic stimuli responsive properties. Here we present supramolecular polymer assemblies resulting from self-assembly of mostly amphiphilic copolymers either as 3D compartments (polymersomes, PICsomes, peptosomes), or as planar membranes (free standing films, solid-supported membranes, membrane-mimetic brushes). In a bioinspired strategy, such synthetic assemblies decorated with biomolecules by insertion/encapsulation/attachment, serve for development of multifunctional systems. In addition, when the assemblies are stimuli-responsive, their architecture and properties change in the presence of stimuli, and release a cargo or allow "on demand" a specific in situ reaction. Relevant examples are included for an overview of bioinspired polymer compartments with nanometre sizes and membranes as candidates in applications ranging from drug delivery systems, up to artificial organelles, or active surfaces. Both the advantages of using polymer supramolecular assemblies and their present limitations are included to serve as a basis for future improvements. PMID- 26563575 TI - Site-Specific N-Terminal Labeling of Peptides and Proteins using Butelase 1 and Thiodepsipeptide. AB - An efficient ligase with exquisite site-specificity is highly desirable for protein modification. Recently, we discovered the fastest known ligase called butelase 1 from Clitoria ternatea for intramolecular cyclization. For intermolecular ligation, butelase 1 requires an excess amount of a substrate to suppress the reverse reaction, a feature similar to other ligases. Herein, we describe the use of thiodepsipeptide substrates with a thiol as a leaving group and an unacceptable nucleophile to render the butelase-mediated ligation reactions irreversible and in high yields. Butelase 1 also accepted depsipeptides as substrates, but unlike a thiodesipeptide, the desipeptide ligation was partially reversible as butelase 1 can tolerate an alcohol group as a poor nucleophile. The thiodesipeptide method was successfully applied in N-terminal labeling of ubiquitin and green fluorescent protein using substrates with or without a biotin group in high yields. PMID- 26563577 TI - Sol-gel synthesis of monolithic materials with hierarchical porosity. AB - The development of synthetic routes to hierarchically organized porous materials containing multiple, discrete sets of pores having disparate length scales is of high interest for a wide range of applications. One possible route towards the formation of multilevel porous architectures relies on the processing of condensable, network forming precursors (sol-gel processes) in the presence of molecular porogens, lyotropic mesophases, supramolecular architectures, emulsions, organic polymers, or ice. In this review the focus is on sol-gel processing of inorganic and organic precursors with concurrently occurring microscopic and/or macroscopic phase separation for the formation of self supporting monoliths. The potential and the limitations of the solution-based approaches is presented with special emphasis to recent examples of hierarchically organized silica, metal oxides and phosphates as well as carbon monoliths. PMID- 26563576 TI - Broadband All-Polymer Phototransistors with Nanostructured Bulk Heterojunction Layers of NIR-Sensing n-Type and Visible Light-Sensing p-Type Polymers. AB - We report 'broadband light-sensing' all-polymer phototransistors with the nanostructured bulk heterojunction (BHJ) layers of visible (VIS) light-sensing electron-donating (p-type) polymer and near infrared (NIR) light-sensing electron accepting (n-type) polymer. Poly[{2,5-bis-(2-ethylhexyl)-3,6-bis-(thien-2-yl) pyrrolo[3,4-c]pyrrole-1,4-diyl}-co-{2,2'-(2,1,3-benzothiadiazole)]-5,5'-diyl}] (PEHTPPD-BT), which is synthesized via Suzuki coupling and employed as the n-type polymer, shows strong optical absorption in the NIR region (up to 1100 nm) in the presence of weak absorption in the VIS range (400~600 nm). To strengthen the VIS absorption, poly(3-hexylthiophene) (P3HT) is introduced as the p-type polymer. All-polymer phototransistors with the BHJ (P3HT:PEHTPPD-BT) layers, featuring a peculiar nano-domain morphology, exhibit typical p-type transistor characteristics and efficiently detect broadband (VIS~NIR) lights. The maximum corrected responsivity (without contribution of dark current) reaches up to 85~88% (VIS) and 26~40% (NIR) of theoretical responsivity. The charge separation process between P3HT and PEHTPPD-BT components in the highest occupied molecular orbital is proposed as a major working mechanism for the effective NIR sensing. PMID- 26563578 TI - From Atomistic Surface Chemistry to Nanocrystals of Functional Chalcogenides. AB - Synthesis and utilization of nanocrystals are highly active fields of current research, but they require a thorough understanding of the underlying crystal surfaces. In this Minireview, we span the arc from surfaces to free nanocrystals, and onward to their chemical synthesis, using as examples lead selenide (PbSe), tin telluride (SnTe), and their direct chemical relatives. Besides experimental insights, we highlight the increasingly influential role played by quantum chemical simulations of surfaces and nanocrystals. What can theory do today, or possibly tomorrow; where are its limits? Answering these questions, and skillfully linking them to experiments, could open up new atomistically (that is, chemically) guided perspectives for nanosynthesis. PMID- 26563579 TI - Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis. AB - Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process. PMID- 26563580 TI - Ultrafast Electron Transfer Kinetics of Graphene Grown by Chemical Vapor Deposition. AB - High electrochemical reactivity is required for various energy and sensing applications of graphene grown by chemical vapor deposition (CVD). Herein, we report that heterogeneous electron transfer can be remarkably fast at CVD-grown graphene electrodes that are fabricated without using the conventional poly(methyl methacrylate) (PMMA) for graphene transfer from a growth substrate. We use nanogap voltammetry based on scanning electrochemical microscopy to obtain very high standard rate constants k(0) >=25 cm s(-1) for ferrocenemethanol oxidation at polystyrene-supported graphene. The rate constants are at least 2-3 orders of magnitude higher than those at PMMA-transferred graphene, which demonstrates an anomalously weak dependence of electron-transfer rates on the potential. Slow kinetics at PMMA-transferred graphene is attributed to the presence of residual PMMA. This unprecedentedly high reactivity of PMMA-free CVD grown graphene electrodes is fundamentally and practically important. PMID- 26563581 TI - Reduced cortical microvascular oxygenation in multiple sclerosis: a blinded, case controlled study using a novel quantitative near-infrared spectroscopy method. AB - Hypoxia (low oxygen) is associated with many brain disorders as well as inflammation, but the lack of widely available technology has limited our ability to study hypoxia in human brain. Multiple sclerosis (MS) is a poorly understood neurological disease with a significant inflammatory component which may cause hypoxia. We hypothesized that if hypoxia were to occur, there should be reduced microvascular hemoglobin saturation (StO2). In this study, we aimed to determine if reduced StO2 can be detected in MS using frequency domain near-infrared spectroscopy (fdNIRS). We measured fdNIRS data in cortex and assessed disability of 3 clinical isolated syndrome (CIS), 72 MS patients and 12 controls. Control StO2 was 63.5 +/- 3% (mean +/- SD). In MS patients, 42% of StO2 values were more than 2 * SD lower than the control mean. There was a significant relationship between StO2 and clinical disability. A reduced microvascular StO2 is supportive (although not conclusive) that there may be hypoxic regions in MS brain. This is the first study showing how quantitative NIRS can be used to detect reduced StO2 in patients with MS, opening the door to understanding how microvascular oxygenation impacts neurological conditions. PMID- 26563582 TI - Inverting the G-Tetrad Polarity of a G-Quadruplex by Using Xanthine and 8 Oxoguanine. AB - G-quadruplexes are four-stranded nucleic acid structures that are built from consecutively stacked guanine tetrad (G-tetrad) assemblies. The simultaneous incorporation of two guanine base lesions, xanthine (X) and 8-oxoguanine (O), within a single G-tetrad of a G-quadruplex was recently shown to lead to the formation of a stable G?G?X?O tetrad. Herein, a judicious introduction of X and O into a human telomeric G-quadruplex-forming sequence is shown to reverse the hydrogen-bond polarity of the modified G-tetrad while preserving the original folding topology. The control exerted over G-tetrad polarity by joint X?O modification will be valuable for the design and programming of G-quadruplex structures and their properties. PMID- 26563583 TI - Messengers from the deep: Fossil wadsleyite-chromite microstructures from the Mantle Transition Zone. AB - Investigations of the Mantle Transition Zone (MTZ; 410-660 km deep) by deformation experiments and geophysical methods suggest that the MTZ has distinct rheological properties, but their exact cause is still unclear due to the lack of natural samples. Here we present the first direct evidence for crystal-plastic deformation by dislocation creep in the MTZ using a chromitite from the Luobusa peridotite (E. Tibet). Chromite grains show exsolution of diopside and SiO2, suggesting previous equilibration in the MTZ. Electron backscattered diffraction (EBSD) analysis reveals that olivine grains co-existing with exsolved phases inside chromite grains and occurring on chromite grain boundaries have a single pronounced crystallographic preferred orientation (CPO). This suggests that olivine preserves the CPO of a high-pressure polymorph (wadsleyite) before the high-pressure polymorph of chromite began to invert and exsolve. Chromite also shows a significant CPO. Thus, the fine-grained high-pressure phases were deformed by dislocation creep in the MTZ. Grain growth in inverted chromite produced an equilibrated microstructure during exhumation to the surface, masking at first sight its MTZ deformation history. These unique observations provide a window into the deep Earth, and constraints for interpreting geophysical signals and their geodynamic implications in a geologically robust context. PMID- 26563584 TI - Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin. AB - To reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, we created a "genetic dereplication" strain in which we deleted eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total). This strain allowed us to discover a novel compound that we designate aspercryptin and to propose a biosynthetic pathway for the compound. Interestingly, aspercryptin is formed from compounds produced by two separate gene clusters, one of which makes the well-known product cichorine. This raises the exciting possibility that fungi use differential regulation of expression of secondary metabolite gene clusters to increase the diversity of metabolites they produce. PMID- 26563585 TI - CalQuo: automated, simultaneous single-cell and population-level quantification of global intracellular Ca2+ responses. AB - Detecting intracellular calcium signaling with fluorescent calcium indicator dyes is often coupled with microscopy techniques to follow the activation state of non excitable cells, including lymphocytes. However, the analysis of global intracellular calcium responses both at the single-cell level and in large ensembles simultaneously has yet to be automated. Here, we present a new software package, CalQuo (Calcium Quantification), which allows the automated analysis and simultaneous monitoring of global fluorescent calcium reporter-based signaling responses in up to 1000 single cells per experiment, at temporal resolutions of sub-seconds to seconds. CalQuo quantifies the number and fraction of responding cells, the temporal dependence of calcium signaling and provides global and individual calcium-reporter fluorescence intensity profiles. We demonstrate the utility of the new method by comparing the calcium-based signaling responses of genetically manipulated human lymphocytic cell lines. PMID- 26563587 TI - A Filled-Honeycomb-Structured Crystal Formed by Self-Assembly of a Janus Polyoxometalate-Silsesquioxane (POM-POSS) Co-Cluster. AB - Clusters with diverse structures and functions have been used to create novel cluster-assembled materials (CAMs). Understanding their self-assembly process is a prerequisite to optimize their structure and function. Herein, two kinds of unlike organo-functionalized inorganic clusters are covalently linked by a short organic tether to form a dumbbell-shaped Janus co-cluster. In a mixed solvent of acetonitrile and water, it self-assembles into a crystal with a honeycomb superstructure constructed by hexagonal close-packed cylinders of the smaller cluster and an orderly arranged framework of the larger cluster. Reconstruction of these structural features via coarse-grained molecular simulations demonstrates that the cluster crystallization and the nanoscale phase separation between the two incompatible clusters synergistically result in the unique nano architecture. Overall, this work opens up new opportunities for generating novel CAMs for advanced future applications. PMID- 26563588 TI - Quasi suppression of higher-order diffractions with inclined rectangular apertures gratings. AB - Advances in the fundamentals and applications of diffraction gratings have received much attention. However, conventional diffraction gratings often suffer from higher-order diffraction contamination. Here, we introduce a simple and compact single optical element, named inclined rectangular aperture gratings (IRAG), for quasi suppression of higher-order diffractions. We show, both in the visible light and soft x-ray regions, that IRAG can significantly suppress higher order diffractions with moderate diffraction efficiency. Especially, as no support strut is needed to maintain the free-standing patterns, the IRAG is highly advantageous to the extreme-ultraviolet and soft x-ray regions. The diffraction efficiency of the IRAG and the influences of fabrication constraints are also discussed. The unique quasi-single order diffraction properties of IRAG may open the door to a wide range of photonic applications. PMID- 26563586 TI - Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification. AB - To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli 341-534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon sequencing. Through comparisons of microbial taxonomic counts from paired amplicon (V3 U341F/534R) and shotgun sequencing datasets, we demonstrate that extensive length polymorphisms in the V3 region are a consistent and major cause of differential amplification leading to taxonomic bias in ancient microbiome reconstructions based on amplicon sequencing. We conclude that systematic amplification bias confounds attempts to accurately reconstruct microbiome taxonomic profiles from 16S rRNA V3 amplicon data generated using universal primers. Because in silico analysis indicates that alternative 16S rRNA hypervariable regions will present similar challenges, we advocate for the use of a shotgun metagenomics approach in ancient microbiome reconstructions. PMID- 26563589 TI - [Mineral-based alkaline waters' prescription in France: Patients are the key point for both nephrologists and urologists]. AB - Alkali therapy is frequently used during chronic kidney disease and nephrolithiasis: nephrologists and urologists are the key operators. Very few is known about the underlying conditions of such a prescription: the aim of this study was to delineate those determinants. We conducted a prospective survey where French nephrologists and urologists were involved. Responders were without gender distinction and principally nephrologists. Prescription frequency was associated with gender (women), specialty (nephrologists), indications and perceived efficiency. Urologists prescribe more often during nephrolithiasis and nephrologists during chronic kidney disease. Urologists were more expert (by scoring on mineral-based alkaline waters compositions knowledge). By multivariate analysis, prescription frequency is associated with gender (women), indications and perceived efficiency by prescribers, which is itself influenced by feedback from patients. These results could have been influenced by a huge representation of nephrologists but foster physicians to go on listening to feedback from patients, due to a lack of clinical trials on the efficiency of mineral-based alkaline waters in such a field. Finally, physicians' education (especially young nephrologists) on mineral-based alkaline waters should be intensified. PMID- 26563591 TI - Structural Changes and Aggregation Mechanisms for Anti-Streptavidin IgG1 at Elevated Concentration. AB - Non-native protein aggregation may occur during manufacturing and storage of protein therapeutics, and this may decrease drug efficacy or jeopardize patient safety. From a regulatory perspective, changes in higher order structure due to aggregation are of particular interest but can be difficult to monitor directly at elevated protein concentrations. The present report focuses on non-native aggregation of antistreptavidin (AS) IgG1 at 30 mg/mL under solution conditions that prior work at dilute concentrations (e.g., 1 mg/mL) indicated would result in different aggregation mechanisms. Time-dependent aggregation and structural changes were monitored in situ with dynamic light scattering, small-angle neutron scattering, and Raman scattering and ex situ with far-UV circular dichroism and second-derivative UV spectroscopy. The effects of adding 0.15 M (~5 w/w %) sucrose were also assessed. The addition of sucrose decreased monomer loss rates but did not change protein-protein interactions, aggregation mechanism(s), or aggregate structure and morphology. Consistent with prior results, altering the pD or salt concentration had the primary effect of changing the aggregation mechanism. Overall, the results provide a comparison of aggregate structure and morphology created via different growth mechanisms using orthogonal techniques and show that the techniques agree at least qualitatively. Interestingly, AS-IgG1 aggregates created at pD 5.3 with no added salt formed the smallest aggregates but had the largest structural changes compared to other solution conditions. The observation that the larger aggregates were also those with less structural perturbation compared to folded AS-IgG1 might be expected to extend to other proteins if the same strong electrostatic repulsions that mediate aggregate growth also mediate structural changes of the constituent proteins within aggregates. PMID- 26563590 TI - High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry. AB - AIMS: Dementia and type 2 diabetes (T2D) are two major phenomena in older people. To compare anti-hyperglycemic therapy and diabetes-related comorbidities between elderly T2D patients with or without comorbid dementia. METHODS: 215,932 type 2 diabetes patients aged >= 40 years (median [Q1;Q3]: 70.4 [61.2;77.7] years) from the standardized, multicenter German/Austrian diabetes patient registry, DPV, were studied. To identify patients with comorbid dementia, the registry was searched by ICD-10 codes, DSM-IV/-5 codes, respective search terms and/or disease specific medication. For group comparisons, multiple hierarchic regression modeling with adjustments for age, sex, and duration of diabetes was applied. RESULTS: 3.1% (n=6770; 57% females) of the eligible T2D patients had clinically recognized comorbid dementia. After adjustment for demographics, severe hypoglycemia (insulin group: 14.8 +/- 0.6 vs. 10.4 +/- 0.2 events per 100 patient years, p<0.001), hypoglycemia with coma (insulin group: 7.6 +/- 0.4 vs. 3.9 +/- 0.1 events per 100 patient-years, p<0.001), depression (9.9 vs. 4.7%, p<0.001), hypertension (74.7 vs. 72.2%, p<0.001), stroke (25.3 vs. 6.5%, p<0.001), diabetic foot syndrome (6.0 vs. 5.2%, p=0.004), and microalbuminuria (34.7 vs. 32.2%, p<0.001) were more common in dementia patients compared to T2D without dementia. Moreover, patients with dementia received insulin therapy more frequently (59.3 vs. 54.7%, p<0.001), but metabolic control (7.7 +/- 0.1 vs. 7.7 +/- 0.1%) was comparable to T2D without dementia. CONCLUSIONS: In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia. PMID- 26563592 TI - Raman spectroscopy for cancer diagnosis: how far have we come? AB - Raman spectroscopy is increasingly investigated for cancer diagnosis. As the potential of the technique is explored and realized, it is slowly making its way into clinics. There are more reports in recent years showing promise that it can help clinicians for cancer diagnosis. However, a number of challenges remain to be overcome, especially in vivo cancer diagnosis. In this article, the recent progress of the technique toward clinical cancer diagnosis is discussed from a critical perspective. PMID- 26563593 TI - Validation of a new method for measuring and continuously monitoring the efficiency of industrial flares. AB - A new method has been developed for a direct and remote measurement of industrial flare combustion efficiency (CE). The method is based on a unique hyper-spectral or multi-spectral Infrared (IR) imager which provides a high frame rate, high spectral selectivity and high spatial resolution. The method can be deployed for short-term flare studies or for permanent installation providing real-time continuous flare CE monitoring. In addition to the measurement of CE, the method also provides a measurement for level of smoke in the flare flame regardless of day or night. The measurements of both CE and smoke level provide the flare operator with a real-time tool to achieve "incipient smoke point" and optimize flare performance. The feasibility of this method was first demonstrated in a bench scale test. The method was recently tested on full scale flares along with extractive sampling methods to validate the method. The full scale test included three types of flares - steam assisted, air assisted, and pressure assisted. Thirty-nine test runs were performed covering a CE range of approximately 60 100%. The results from the new method showed a strong agreement with the extractive methods (r(2)=0.9856 and average difference in CE measurement=0.5%). IMPLICATIONS: Because industrial flares are operated in the open atmosphere, direct measurement of flare combustion efficiency (CE) has been a long-standing technological challenge. Currently flare operators do not have feedback in terms of flare CE and smoke level, and it is extremely difficult for them to optimize flare performance and reduce emissions. The new method reported in this paper could provide flare operators with real-time data for CE and smoke level so that flare operations can be optimized. In light of EPA's focus on flare emissions and its new rules to reduce emissions from flares, this policy-relevant development in flare CE monitoring is brought to the attention of both the regulating and regulated communities. PMID- 26563594 TI - [Advance care planning: Results of implementation program in nursing homes]. PMID- 26563595 TI - The hematopoietic tumor suppressor interferon regulatory factor 8 (IRF8) is upregulated by the antimetabolite cytarabine in leukemic cells involving the zinc finger protein ZNF224, acting as a cofactor of the Wilms' tumor gene 1 (WT1) protein. AB - The transcription factor interferon regulatory factor-8 (IRF8) is highly expressed in myeloid progenitors, while most myeloid leukemias show low or absent expression. Loss of IRF8 in mice leads to a myeloproliferative disorder, indicating a tumor-suppressive role of IRF8. The Wilms tumor gene 1 (WT1) protein represses the IRF8-promoter. The zinc finger protein ZNF224 can act as a transcriptional co-factor of WT1 and potentiate the cytotoxic response to the cytostatic drug cytarabine. We hypothesized that cytarabine upregulates IRF8 and that transcriptional control of IRF8 involves WT1 and ZNF224. Treatment of leukemic K562 cells with cytarabine upregulated IRF8 protein and mRNA, which was correlated to increased expression of ZNF224. Knock down of ZNF224 with shRNA suppressed both basal and cytarabine-induced IRF8 expression. While ZNF224 alone did not affect IRF8 promoter activity, ZNF224 partially reversed the suppressive effect of WT1 on the IRF8 promoter, as judged by luciferase reporter experiments. Coprecipitation revealed nuclear binding of WT1 and ZNF224, and by chromatin immunoprecipitation (ChIP) experiments it was demonstrated that WT1 recruits ZNF224 to the IRF8 promoter. We conclude that cytarabine-induced upregulation of the IRF8 in leukemic cells involves increased levels of ZNF224, which can counteract the repressive activity of WT1 on the IRF8-promoter. PMID- 26563596 TI - Increased temperature tolerance of the air-breathing Asian swamp eel Monopterus albus after high-temperature acclimation is not explained by improved cardiorespiratory performance. AB - This study investigated the hypothesis that in the Asian swamp eel Monopterus albus, an air-breathing fish from south-east Asia that uses the buccopharyngeal cavity for oxygen uptake, the upper critical temperature (TU) is increased by acclimation to higher temperature, and that the increased TU is associated with improved cardiovascular and respiratory function. Monopterus albus were therefore acclimated to 27 degrees C (current average) and 32 degrees C (current maximum temperature as well as projected average within 100-200 years), and both the effect of acclimation and acute temperature increments on cardiovascular and respiratory functions were investigated. Two weeks of heat acclimation increased upper tolerated temperature (TU ) by 2 degrees C from 36.9 +/- 0.1 degrees C to 38.9 +/- 0.1 degrees C (mean +/- s.e.). Oxygen uptake (MO2) increased with acclimation temperature, accommodated by increases in both aerial and aquatic respiration. Overall, MO2 from air (MO2a ) was predominant, representing 85% in 27 degrees C acclimated fish and 80% in 32 degrees C acclimated fish. MO2 increased with acute increments in temperature and this increase was entirely accommodated by an increase in air-breathing frequency and MO2a . Monopterus albus failed to upregulate stroke volume; rather, cardiac output was maintained through increased heart rate with rising temperature. Overall, acclimation of M. albus to 32 degrees C did not improve its cardiovascular and respiratory performance at higher temperatures, and cardiovascular adaptations, therefore, do not appear to contribute to the observed increase in TU. PMID- 26563597 TI - Accuracy of student performance while reading leveled books rated at their instructional level by a reading inventory. AB - Identifying a student's instructional level is necessary to ensure that students are appropriately challenged in reading. Informal reading inventories (IRIs) purport to assess the highest reading level at which a student can accurately decode and comprehend text. However, the use of IRIs in determining a student's instructional level has been questioned because of a lack of research. The current study examined the percentage of words read correctly with 64 second- and third-grade students while reading from texts at their instructional level as determined by an IRI. Students read for 1 min from three leveled texts that corresponded to their instructional level as measured by an IRI, and the percentage of words read correctly was recorded. The percentage read correctly correlated across the three books from r=.47 to r=.68 and instructional level categories correlated from tau=.59 to tau=.65. Percent agreement calculations showed that the categorical scores (frustration, instructional, and independent) for the three readings agreed approximately 67% to 70% of the time, which resulted in a kappa estimate of less than .50. Kappa coefficients of .70 are considered strong indicators of agreement. Moreover, more than half of the students with the lowest reading skills read at a frustration level when attempting to read books rated at their instructional level by an IRI. The current study questions how reliably and accurately IRIs identify students' instructional level for reading. PMID- 26563598 TI - Measurement and structural relations of an authoritative school climate model: A multi-level latent variable investigation. AB - This study tested a conceptual model of school climate in which two key elements of an authoritative school, structure and support variables, are associated with student engagement in school and lower levels of peer aggression. Multilevel multivariate structural modeling was conducted in a statewide sample of 48,027 students in 323 public high schools who completed the Authoritative School Climate Survey. As hypothesized, two measures of structure (Disciplinary Structure and Academic Expectations) and two measures of support (Respect for Students and Willingness to Seek Help) were associated with higher student engagement (Affective Engagement and Cognitive Engagement) and lower peer aggression (Prevalence of Teasing and Bullying) on both student and school levels of analysis, controlling for the effects of school demographics (school size, percentage of minority students, and percentage of low income students). These results support the extension of authoritative school climate model to high school and guide further research on the conditions for a positive school climate. PMID- 26563599 TI - Promoting social-emotional competence: An evaluation of the elementary version of Second Step(r). AB - Research has consistently linked social-emotional skills to important educational and life outcomes. Many children begin their school careers, however, without the requisite social and emotional skills that facilitate learning, which has prompted schools nationwide to adopt specific curricula to teach students the social-emotional skills that enable them to maintain optimal engagement in the learning process. Second Step(r) is one of the most widely disseminated social emotional learning (SEL) programs; however, its newly revised version has never been empirically evaluated. The purpose of this study was to conduct a randomized controlled trial investigating the impact of the 4th Edition Second Step(r) on social-behavioral outcomes over a 1-year period when combined with a brief training on proactive classroom management. Participants were kindergarten to 2nd grade students in 61 schools (321 teachers, 7300 students) across six school districts. Hierarchical models (time*condition) suggest that the program had few main effects from teacher-reported social and behavioral indices, with small effect sizes. The majority of significant findings were moderated effects, with 8 out of 11 outcome variables indicating the intervention-produced significant improvements in social-emotional competence and behavior for children who started the school year with skill deficits relative to their peers. All the significant findings were based on teacher-report data highlighting a need for replication using other informants and sources of data. Findings provide program validation and have implications for understanding the reach of SEL programs. PMID- 26563600 TI - Life Satisfaction and Academic Performance in Early Adolescents: Evidence for Reciprocal Association. AB - Student subjective well-being remains a relatively neglected topic despite its intimate link to positive school outcomes. As academic achievement is a widely used yardstick of student success and school accountability, school-based mental health research and practice have focused primarily on the assessment and treatment of learning and behavioral problems. This short-term longitudinal study sought to establish the role of student subjective well-being, specifically, global life satisfaction (LS), in academic achievement. Based on the engine model of well-being (Jayawickreme, Forgeard, & Seligman, 2012), the study focused on LS as a process variable and academic performance as an outcome variable and vice versa. Using two waves (five months apart) of data, the study examined the reciprocal relations between LS and academic achievement, and how the relations may be shaped by positive and negative affective experiences in school, in a sample of 821 middle school students. Results revealed positive reciprocal causal relations between students' LS and grades, even when demographic covariates, school-based positive and negative affect, and baseline values of the criterion variables were controlled. This study provides empirical support that LS does not undermine academic achievement (or vice versa), but rather it is synergistic with better school grades. Furthermore, the relations between students' LS and grades were not moderated by negative or positive affective experiences in school. These findings suggest that student LS should occupy a more prominent niche in the school agenda. PMID- 26563601 TI - Effect of school belonging trajectories in grades 6-8 on achievement: Gender and ethnic differences. AB - This study investigated the association between trajectories of school belonging across grades 6-8 and academic achievement in grade 8 in an ethnically diverse sample of 527 academically at-risk adolescents. Students reported annually on school belonging. Reading and math achievement were assessed at grade 5 (baseline) and grade 8. Interactive effects of gender and ethnicity were found in the conditional growth models for school belonging. Girls of all ethnicities had identical growth trajectories and reported higher initial school belonging than Euro-American or Latino boys. Latino and Euro-American males had lower initial level of school belonging than African American males, and Latino males had lower growth in school belonging than Euro-American males. In structural equation modeling (SEM) analyses, initial level of school belonging predicted grade 8 reading for girls and grade 8 math for boys and girls, above prior achievement and school and child covariates, but growth in school belonging predicted grade 8 achievement only for African American students. Implications for strategies to improve school belonging among academically at-risk youth are discussed. PMID- 26563602 TI - Multiplexed MALDI-MS arrays for screening of MIP solid phase extraction materials. AB - Technology that facilitates rapid investigation of solid phase extraction protocols using very small amounts of sorbent can save both time and money. The microfabricated ISET (Integrated Selective Enrichment Target) interfaced with MALDI mass spectrometry is able to provide an efficient, economic and generic optimization process for SPE sample preparation. The SPE is performed in a rapid and parallel fashion, with a processing time off only 2h per ISET with 96 samples. Each of the 96 wells on the ISET can hold 600nL of SPE sorbent. The ability to work with small amounts of sorbent and samples in the ISET platform provides a big advantage when developing affinity sorbents, such as molecularly imprinted polymers (MIPs). Here it is demonstrated that an amount of 25mg phosphoserine imprinted MIP (pS-MIP) sorbent can allow for analysis of more than 500 ISET nanovials using a multitude of different conditions. In the presented case, the multiplexed experiments allowed for early discovery of unspecific interactions and subsequent minimization of these, resulting in a protocol that provided improved enrichment of phosphopeptides. PMID- 26563603 TI - Transorbital neuroendoscopic surgery for the treatment of skull base lesions. AB - Transorbital neuroendoscopic surgery (TONES) is a relatively new technique that not only allows access to the contents of the orbit but also the intracranial compartment, including the anterior cranial fossa, middle fossa and lateral cavernous sinus. In this study, we aimed to retrospectively review the largest experience to our knowledge with regards to surgical outcomes of skull base pathologies treated with a TONES procedure. Forty patients (aged 3-89 years) underwent 45 TONES procedures between the years of 2006-2013. Pathologies were cerebrospinal fluid leak repair (n=16), traumatic fracture (n=8), tumor (n=11), meningoencephalocele (n=5), hematoma (n=1), and infection (n=4). Three patients had a persistent complication at 3 months, including a case each of enophthalmos (unnoticed by patient), epiphora (delayed presentation at 2 months requiring dacryocystorhinostomy), and ptosis (improved at 1 year). Surgical success was achieved in all patients. Of special import, there were no cases of visual decline, diplopia, or stroke. There was no mortality. To our knowledge this is the first study and largest experience of TONES (level 4 evidence) to detail outcomes with respect to skull base pathologies. Our results indicate that TONES procedures can be performed with minimal morbidity. Further studies are needed to assess equivalency with craniotomy based approaches though this initial report is encouraging. PMID- 26563604 TI - Intradural chordoma presenting with intratumoral bleeding. AB - Intradural clival chordomas are very rare, and only 29 cases have been reported to our knowledge. They arise purely intradurally without bone or dural involvement and may differ from classic clival chordomas in physiopathology and management. We present a 28-year-old woman who presented with intradural clival chordoma and tumoral bleeding. After initial gross macroscopic surgical resection, she presented with tumor recurrence after 2 years, again with intratumoral bleeding. Although usually considered to have a more favorable prognosis in comparison to typical chordomas, intradural chordomas appear to behave as typical chordomas. Intratumoral bleeding may be a sign of an aggressive lesion and risk of recurrence. We highlight the differential diagnosis of intrinsic posterior fossa bleeding, especially in young patients. Intradural chordomas may be underdiagnosed and incorrectly treated as other types of parenchymal hemorrhage. PMID- 26563605 TI - What influences the age of menopause? PMID- 26563606 TI - Is the association between insulin resistance and diabetogenic haematopoietically expressed homeobox (HHEX) polymorphism (rs1111875) affected by polycystic ovary syndrome status? AB - Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) >=2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P<0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33-0.78; P=0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status. PMID- 26563607 TI - Empowerment of young people who have a parent living with dementia: a social model perspective. AB - BACKGROUND: Socially constructed disablement has marginalized young people in families where a parent has younger onset dementia (YOD). This has contributed to inadequate societal support for their complex situation. Impacts on such young people include significant involvement with mental health services for themselves. In this paper, we explored the young people's lived experiences in these families and the influencing factors to enable these young people to be included and supported within their community. METHODS: In this qualitative research study, the social model of disability was used as the theoretical framework in conducting a thematic analysis of interviews with 12 participants. RESULTS: Three themes emerged; invisibility highlighting the issues of marginalization; connectivity foregrounding the engagement of young people with family, friends and their social networks, and being empowered through claiming their basic human right to receive the age appropriate support they needed. CONCLUSION: The current plight of young people living with a parent with YOD demands a fundamental shift by society in developing inclusive cross-sectorial cooperation linking service providers across youth and dementia sectors. This requires working in partnership with the service users responding to the identified needs of individual family members. PMID- 26563608 TI - Impact of preoperative continuous femoral blockades on morphine consumption and morphine side effects in hip-fracture patients: A randomized, placebo-controlled study. AB - BACKGROUND: Upon arrival at the emergency department, hip-fracture pain relief is usually carried out via systemic opioids. Continuous nerve blocks are efficient in the postoperative period, but have not been evaluated preoperatively. This study compared the reduction in morphine consumption and related side effects of a continuous femoral block with a single shot block in hip-fracture patients. METHODS: Hip-fracture patients admitted to the emergency department received a femoral nerve catheter, with a single lidocaine injection. They were then randomized to ropivacaine (group R) or saline continuous infusion (placebo, group P) in a double-blind manner. Morphine consumption and side effects were prospectively collected until the 24th postoperative hour. RESULTS: Sixty patients were included and 55 analyzed. There were no significant differences between the 2 groups regarding fracture types, delay before surgery (median [Q1 Q3]: 21.3 [14.5-29.4] versus 20.8 [15.7-36.2] hours for groups R and P, respectively; P=0.87) and catheter duration (47.5 [39.8-52.4] versus 42.5 [32.1 50.5] hours, P=0.29). Total morphine consumption was not significantly decreased in group R (5 [0-14] versus 8 [4.5-11] mg, P=0.3) and pain scores were similar (mean+/-SD; VAS 29+/-15/100 versus 33+/-13, P=0.3). We observed a significant reduction in morphine adverse effects (31% versus 69% for groups R and P, respectively; P<0.01), mainly nausea (31% versus 59%, P=0.03). One morphine side effect could be avoided for every 5 patients treated. CONCLUSION: Preoperative continuous femoral blockades using ropivacaine reduce morphine side effects (mainly nausea) in hip-fracture patients without reducing morphine consumption. PMID- 26563609 TI - [1,4]-sigmatropic rearrangement of chiral nitrones and their utilization in the synthesis of new iminosugars. AB - Reflection on the epimerization of the alpha-stereocenter of sugar nitrones leads to the conclusion that the process may occur through [1,4]-sigmatropic rearrangement. Participation of an ionic mechanism was excluded by a deuterium labeling experiment, and DFT calculations showed a reasonable energy barrier for the proposed [1,4]-shift. Products of the intramolecular 1,3-dipolar cycloaddition of the studied nitrones were utilized in the diversity-oriented synthesis of polyhydroxy derivatives of piperidine, indolizidine and quinolizidine. Minimal activity against the screened glucosidases and human melanoma cell lines was observed for some of the obtained compounds. PMID- 26563610 TI - Dynamic interplay of multidrug transporters with TolC for isoprenol tolerance in Escherichia coli. AB - Engineering of efflux pumps is a promising way to improve host's tolerance to biofuels such as medium-chain alcohols (CmOHs); however, this strategy is restricted by poor understanding of the efflux pumps engaged in extrusion of solvents. In this study, several Escherichia coli mutants of multidrug transporters were evaluated for isoprenol tolerance. Susceptible phenotypes were observed in the mutants with individual deletion of six transporters, AcrD, EmrAB, MacAB, MdtBC, MdtJI and YdiM, whereas inactivation of AcrAB transporter resulted in an improved tolerance to isoprenol and other CmOHs. AcrAB is the major transporter forming tripartite transperiplasmic complex with outer membrane channel TolC for direct extrusion of toxic molecules in E. coli. The AcrAB inactivation enables to enhance TolC availability for the multidrug transporters associated with extrusion of CmOHs and increase the tolerance to CmOHs including isoprenol. It is assumed that outer membrane channel TolC plays an important role in extrusion of isoprenol and other CmOHs. PMID- 26563611 TI - Is inefficient cognitive processing in anorexia nervosa a familial trait? A neuropsychological pilot study of mothers of offspring with a diagnosis of anorexia nervosa. AB - OBJECTIVES: Inefficient set shifting and poor global processing are thought to be possible traits in anorexia nervosa (AN). This study aimed to investigate the neuropsychological processing style of unaffected mothers of offspring with AN (unaffected AN mothers). METHODS: The performance of 21 unaffected AN mothers were compared to 20 mothers of healthy control offspring on neuropsychological measures of set shifting (Wisconsin Card Sorting Test, WCST) and central coherence (Fragmented Pictures Task, FPT, and Rey Osterrieth Complex Figures Task, ROCFT). Associations between neuropsychological performance and clinical measures were examined in the unaffected AN mothers group. RESULTS: There were significant differences in perseverative errors on the WCST (P<=0.01), with the unaffected mothers displaying a more inflexible thinking style compared to the control group. There were also significant differences on the FPT (P <= 0.01) and the ROCFT (P <= 0.01), whereby unaffected AN mothers showed lower levels of global processing. CONCLUSIONS: The results of this study support the idea of the familial nature of cognitive styles in AN. The implications of these findings are discussed. PMID- 26563613 TI - [Economic evaluation studies in diagnostic imaging: justification and critical reading]. AB - First, this article describes the concepts and tools most widely used for economic evaluation in healthcare. Second, it discusses some elements that must be taken into account in the social decision about how much we are willing to spend to prolong a person's life by one year. Third, it describes the criteria recommended for the critical analysis of publications that evaluate the economic aspects of health interventions. Finally, several studies about ultrasound screening for aneurysms of the abdominal aorta are used as illustrative examples to show how these elements and criteria can be applied. PMID- 26563612 TI - Serum amyloid A inhibits RANKL-induced osteoclast formation. AB - When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis. PMID- 26563614 TI - SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS. AB - Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disorder that is characterized by the selective death of motor neurons. While the fundamental cause of the disorder is still unclear, the first identified risk gene, Cu,Zn superoxide dismutase (SOD1), has led to the proposal of several mechanisms that are relevant to its pathogenesis. These include excitotoxicity, oxidative stress, ER stress, mitochondrial dysfunction, axonal transport disruption, prion-like propagation, and non-cell autonomous toxicity of neuroglia. Recent evidence suggests that the toxicity of the misfolded wild-type SOD1 (SOD1(WT)) is involved in the pathogenesis of sporadic cases. Yet to what extent SOD1 contributes to neurotoxicity in ALS cases generally is unknown. This review discusses the toxic mechanisms of mutant SOD1 (SOD1(mut)) and misfolded SOD1(WT) in the context of ALS as well as the potential implication of these mechanisms in SOD1 mutation negative ALS. PMID- 26563615 TI - Visualization of polymer relaxation in viscoelastic turbulent micro-channel flow. AB - In micro-channels, the flow of viscous liquids e.g. water, is laminar due to the low Reynolds number in miniaturized dimensions. An aqueous solution becomes viscoelastic with a minute amount of polymer additives; its flow behavior can become drastically different and turbulent. However, the molecules are typically invisible. Here we have developed a novel visualization technique to examine the extension and relaxation of polymer molecules at high flow velocities in a viscoelastic turbulent flow. Using high speed videography to observe the fluorescein labeled molecules, we show that viscoelastic turbulence is caused by the sporadic, non-uniform release of energy by the polymer molecules. This developed technique allows the examination of a viscoelastic liquid at the molecular level, and demonstrates the inhomogeneity of viscoelastic liquids as a result of molecular aggregation. It paves the way for a deeper understanding of viscoelastic turbulence, and could provide some insights on the high Weissenberg number problem. In addition, the technique may serve as a useful tool for the investigations of polymer drag reduction. PMID- 26563616 TI - Identification of microRNAs and their corresponding targets involved in the susceptibility interaction of wheat response to Puccinia striiformis f. sp. tritici. AB - MicroRNAs (miRNAs) play very important roles in plant defense responses. However, little is known about their roles in the susceptibility interaction between wheat and Puccinia striiformis f. sp. tritici (Pst). In this study, two miRNA libraries were constructed from the leaves of the cultivar Xingzi 9104 inoculated with the virulent Pst race CYR32 and sterile water, respectively. A total of 1316 miRNA candidates, including 173 known miRNAs that were generated from 98 pre-miRNAs, were obtained. The remaining 1143 miRNA candidates included 145 conserved and 998 wheat-specific miRNAs that were generated from 87 and 1088 pre-miRNAs, respectively. The 173 known and 145 conserved miRNAs were sub-classified into 63 miRNA families. The target genes of wheat miRNAs were also confirmed using degradome sequencing technology. Most of the annotated target genes were related to signal transduction or energy metabolism. Additionally, we found that miRNAs and their target genes form complicated regulation networks. The expression profiles of miRNAs and their corresponding target genes were further analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and the results indicate that some miRNAs are involved in the compatible wheat-Pst susceptibility interaction. Importantly, tae-miR1432 was highly expressed when wheat was challenged with CYR32, and the corresponding target gene, predicted to be a calcium ion-binding protein, also exhibited upregulated expression but a divergent expression trend. PC-3P-7484, a specific wheat miRNA, was highly expressed in the wheat response to Pst infection, while the expression of the corresponding target gene ubiquillin was dramatically downregulated. These data provide the foundation for evaluating the important regulatory roles of miRNAs in wheat-Pst susceptibility interaction. PMID- 26563617 TI - Reciprocal preening and food sharing in colour-polymorphic nestling barn owls. AB - Barn owl (Tyto alba) siblings preen and offer food items to one another, behaviours that can be considered prosocial because they benefit a conspecific by relieving distress or need. In experimental broods, we analysed whether such behaviours were reciprocated, preferentially exchanged between specific phenotypes, performed to avoid harassment and food theft or signals of hierarchy status. Three of the results are consistent with the hypothesis of direct reciprocity. First, food sharing was reciprocated in three-chick broods but not in pairs of siblings, that is when nestlings could choose a partner with whom to develop a reciprocating interaction. Second, a nestling was more likely to give a prey item to its sibling if the latter individual had preened the former. Third, siblings matched their investment in preening each other. Manipulation of age hierarchy showed that food stealing was directed towards older siblings but was not performed to compensate for a low level of cooperation received. Social behaviours were related to melanin-based coloration, suggesting that animals may signal their propensity to interact socially. The most prosocial phenotype (darker reddish) was also the phenotype that stole more food, and the effect of coloration on prosocial behaviour depended upon rank and sex, suggesting that colour-related prosociality is state dependent. PMID- 26563619 TI - [The Effect of Tadalafil on Sexual Function, Urinary Function and Health-Related Quality of Life in Patients Treated with Brachytherapy]. AB - OBJECTIVES: We compared sexual function by the expanded prostate cancer index composite (sexual domains of EPIC), health-related quality of life (SF-8), and International Prostate Symptom Score (I-PSS) inpatients using tadalafil after prostate brachytherapy (PB). Forty-five patients who underwent PB between April 2011 and January 2014 were included in this study. Patients were divided into the tadalafil (20 mg,once/week or once/two weeks) treated and non-treated (NT) groups. Sexual function was assessed prior to PB treatment and followed up to 24 weeks after PB. SF-8, sexual domains of EPIC, IPSS and subjective symptoms were assessed pre-PB and at 4, 8, 16, and 24 weeks post-PB. Patients in the tadalafil group achieved higher sexual function scores compared to NT group at all time points. For SF8, the patients in the tadalafil group significantly improved in mental health by the eighth week, and significantly worsened in the NT group (8 w ; p = 0.04). The voiding domains of EPIC score were found to worsen significantly after 4 weeks from PB in both groups, but the score tended to improve over 24 weeks. There was no significant difference between two groups. The I-PSS total score was found to worsen significantly in both groups post-PB, but the tadalafil group had a tendency to worsen less. PB treatment of localized prostate cancer is preferred for the preservation of sexual function. Management of sexual dysfunction with tadalafil after PB does not worsen sexual functions. We concluded that tadalafil might be applicable to mental health care in the treatment of patients with a high interest in sexual function before PB. PMID- 26563618 TI - Environmental boundaries as a mechanism for correcting and anchoring spatial maps. AB - Ubiquitous throughout the animal kingdom, path integration-based navigation allows an animal to take a circuitous route out from a home base and using only self-motion cues, calculate a direct vector back. Despite variation in an animal's running speed and direction, medial entorhinal grid cells fire in repeating place-specific locations, pointing to the medial entorhinal circuit as a potential neural substrate for path integration-based spatial navigation. Supporting this idea, grid cells appear to provide an environment-independent metric representation of the animal's location in space and preserve their periodic firing structure even in complete darkness. However, a series of recent experiments indicate that spatially responsive medial entorhinal neurons depend on environmental cues in a more complex manner than previously proposed. While multiple types of landmarks may influence entorhinal spatial codes, environmental boundaries have emerged as salient landmarks that both correct error in entorhinal grid cells and bind internal spatial representations to the geometry of the external spatial world. The influence of boundaries on error correction and grid symmetry points to medial entorhinal border cells, which fire at a high rate only near environmental boundaries, as a potential neural substrate for landmark-driven control of spatial codes. The influence of border cells on other entorhinal cell populations, such as grid cells, could depend on plasticity, raising the possibility that experience plays a critical role in determining how external cues influence internal spatial representations. PMID- 26563620 TI - [A Case of Retroperitoneal Tumor in the Adrenal Area Turned Out to Be Schwannoma Mimicking an Adrenal Malignant Tumor]. AB - A 76-year-old woman was found to have bilateral suprarenal tumors, 6.5 cm in diameter on the right side, and 2.4 cm in diameter on the left side, by ultrasonography, computed tomography, and magnetic resonance imaging. Strong accumulation of fluorodeoxyglucose in these tumors was found on positron emission tomography. Since it mimicked an adrenal malignant tumor, we performed right adrenalectomy. The pathological diagnosis of the removed mass was benign schwannoma, consistent of the Antoni type A. The left suprarenal tumor was not removed and she has been followed up for 18 months without any recurrence or tumor increase. PMID- 26563621 TI - [A Case of renal Lymphangiectasia with a Follow-Up Duration of Twelve Years]. AB - Renal lymphangiectasia is a rare disorder of renal lymphatics, which is not well known in terms of its natural history. A 54-year-old woman without any symptoms was referred to our department for huge cystic lesions surrounding bilateral kidneys. Imaging examinations with ultrasonography, and computed tomography suggested renal lymphangiectasia of bilateral kidneys. These cystic lesions were increased in size 12 years later, compared with previous magnetic resonance imaging. This finding suggested the slow growing nature of renal lympahngioectasia. PMID- 26563622 TI - [Two Cases of Intrapelvic Schwannoma]. AB - A 67-year-old man (case 1) and 65-year-old man (case 2) were incidentally found to have a tumor in the retrovesical region. Computed tomography and magnetic resonance imaging demonstrated a solid tumor at the right side of the rectum. 2 Deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) -positron emission tomography revealed uptake at the tumor. Both patients were cured by tumor resection. Histological diagnosis was benign schwannoma. In case 2, it was difficult to diagnose the tumor as schwannoma by imaging studies. We made a histological diagnosis by transrectal needle biopsy of the tumor before the operation. Schwannoma is located mostly in the limbs and the head and neck, but rarely in the intrapelvic cavity. We expect that the transrectal needle biopsy is valuable for diagnosing the retrovesical tumor. PMID- 26563623 TI - [A Case of Holmium: YAG Laser Resection of Superficial Bladder Tumor (HoLRBT)]. AB - We present a case of holmium : YAG laser resection of superficial bladder tumor (HoLRBT). A 73-year-old male was referred to our hospital with elevated prostatic specific antigen. Due to difficulty of urination, holmium : YAG laser enucleation of the prostate was performed under the diagnosis of benign prostatic hyperplasia. During the surgery, superficial bladder tumor was incidentally identified, and HoLRBT was performed. After the operation, histopathological examination revealed urothelial carcinoma, G2 > G1, pTa. The patient has been subsequently followed up for 9 months, and there areno evidence of recurrence. Changing the holmium : YAG laser energy setting can potentially be effective and safe to approach a superficial bladder tumor. PMID- 26563624 TI - [The Combination Therapy of Gemcitabine Plus Paclitaxel Induced Complete Response in a Tongue Skin Brain Metastasis of Bladder Carcinoma: A Case Report]. AB - Tongue, skin and brain metastases of bladder cancer are very rare and few cases have been reported. We report a case of tongue, skin and brain metastases of bladder cancer. A 61-year-old woman was referred to our hospital with gross hematuria. Transurethral resection of the bladder (TURBT), tongue biopsy and skin biopsy were performed. Pathological findings showed urothelial carcinoma, G2, micro papillary variant, pT2> and tongue and skin metastases from urothelial carcinoma of bladder. After three cycles of chemotherapy (gemcitabine plus paclitaxel), tongue and skin metastases disappeared. Cystoscopy revealed no tumor of bladder. Eleven months later, she was admitted to our hospital because of disturbance of consciousness. Magnetic resonance imaging (MRI) showed multiple brain metastases. Rechallenge of chemotherapy (gemcitabine plus paclitaxel) restored from disturbance of consciousness and MRI showed partial response of brain metastases. We performed six additional courses of chemotherapy. Skin, tongue and brain metastases from bladder cancer indicate poor risk. Chemotherapy (gemcitabine plus paclitaxel)could be effective against these matastases. PMID- 26563625 TI - [Traumatic Testicular Rupture Complicated with Hydrocele: A Case Report]. AB - A 17-year-old man presented with right hydrocele because of an athletic injury. His scrotum was hit with a ball 2 months ago while playing baseball. He was diagnosed with post-traumatic hydrocele and underwent needle puncture at another hospital 1 month after the trauma. However, the hydrocele did not improve. Therefore, he was referred to our hospital for surgical treatment. For diagnosis of the traumatic hydrocele testis, a hydrocelectomy was scheduled. When we opened the tunica vaginalis, we realized that the tunica albuginea had been ruptured and the testicular parenchyma had gushed out. We tried to replace all the escaped testicular parenchyma into the tunica albuginea, but it was impossible. Therefore were moved some of the redundant testicular parenchyma, and replaced the remnants into the tunica albuginea. After the operation, right hydrocele and testicular atrophy did not occur. Traumatic testicular rupture complicated with hydrocele is rare. PMID- 26563626 TI - Timing of episiotomy and outcome of a non-instrumental vaginal delivery. AB - INTRODUCTION: The aim of this study was to compare to compare immediate delivery outcome as well as healing, pain, anal incontinence and sexuality in a short-term and a long-term follow up after episiotomy performed before or at crowning in nulliparous women. MATERIAL AND METHODS: This cohort study is a comparison of prospectively collected data evaluating the importance of the timing of episiotomy. Patients with episiotomy performed before crowning (n = 86) and at crowning (n = 404) were compared. Obstetric anal sphincter injuries rate, additional perineal or vaginal trauma, neonatal outcome, episiotomy length, 2nd stage of labor duration, blood loss, infection, hematoma, dehiscence, need for resuturing, pain, painful defecation, resumption of sexual intercourse, dyspareunia, anal incontinence and constipation were assessed immediately after delivery or from responses to questionnaires 24 and 72 h, 10 days, 3 and 6 months postpartum. RESULTS: The groups did not differ in age, body mass index, birthweight, occipito-posterior presentation, shoulder dystocia, or episiotomy type. Significant differences between before crowning and at crowning groups were observed in additional vaginal trauma [26 (30.2%) vs. 66 (16.3%), respectively, p < 0.001], mean episiotomy length (42 mm vs. 36 mm, p < 0.001), and mean estimated blood loss (367 mL vs. 344 mL, p < 0.001). Difference in obstetric anal sphincter injuries rate did not reach statistical significance [0 (0.0%) vs. 7 (1.7%), p = 0.61]. The groups did not differ in additional perineal trauma, pain (Visual Analogue Scale, Verbal Rating Scale and Activities of Daily Living scales), healing complications, sexual functions or anal incontinence in short-term or long-term follow up. CONCLUSIONS: Our results suggest that episiotomy performed at crowning is not associated with worse anatomical or functional delivery outcome, and support a restrictive approach to episiotomy. The effect of episiotomy timing on pelvic organ prolapse development remains to be determined. PMID- 26563627 TI - Highly Diastereoselective Synthesis of Methylenecyclobutanes by Merging Boron Homologation and Boron-Allylation Strategies. AB - A highly diastereoselective synthesis of methylenecyclobutanes possessing a quaternary stereocenter is reported, in which boron homologation of an easily generated cyclobutenylmetal species is performed, followed by an allylation reaction. Combining three steps in a one-pot process further optimized the method, which afforded the expected adducts in excellent yields and stereoselectivity, starting from commercially available 4-bromobutyne. PMID- 26563628 TI - Photoinduced Dynamics and Toxicity of a Cancer Drug in Proximity of Inorganic Nanoparticles under Visible Light. AB - Drug sensitization with various inorganic nanoparticles (NPs) has proved to be a promising and an emergent concept in the field of nanomedicine. Rose bengal (RB), a notable photosensitizer, triggers the formation of reactive oxygen species under green-light irradiation, and consequently, it induces cytotoxicity and cell death. In the present study, the effect of photoinduced dynamics of RB upon complexation with semiconductor zinc oxide NPs is explored. To accomplish this, we successfully synthesized nanohybrids of RB with ZnO NPs with a particle size of 24 nm and optically characterized them. The uniform size and integrity of the particles were confirmed by high-resolution transmission electron microscopy. UV/Vis absorption and steady-state fluorescence studies reveal the formation of the nanohybrids. ultrafast picosecond-resolved fluorescence studies of RB-ZnO nanohybrids demonstrate an efficient electron transfer from the photoexcited drug to the semiconductor NPs. Picosecond-resolved Forster resonance energy transfer from ZnO NPs to RB unravel the proximity of the drug to the semiconductor at the molecular level. The photoinduced ROS formation was monitored using a dichlorofluorescin oxidation assay, which is a conventional oxidative stress indicator. It is observed that the ROS generation under green light illumination is greater at low concentrations of RB-ZnO nanohybrids compared with free RB. Substantial photodynamic activity of the nanohybrids in bacterial and fungal cell lines validated the in vitro toxicity results. Furthermore, the cytotoxic effect of the nanohybrids in HeLa cells, which was monitored by MTT assay, is also noteworthy. PMID- 26563629 TI - Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling. AB - The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability. PMID- 26563630 TI - How to integrate research evidence on patient preferences in pharmaceutical coverage decisions and clinical practice guidelines: A qualitative study among Dutch stakeholders. AB - Despite the increasing number of research publications on patient preferences, their use in healthcare policy-making is limited. Integrating research evidence on patient preferences in policy-making is advocated by some, but several issues are put forward as well. There has been no systematic investigation of the stakeholders' view on this matter so far. Objective is to explore the opinions of Dutch stakeholders on how to integrate evidence on patient preferences in pharmaceutical coverage decisions and clinical practice guideline (CPG) development, and which issues may be encountered. METHODS: Qualitative study with semi-structured interviews with Dutch researchers (N=7), policy-makers and CPG developers (N=4) and patient representatives (N=4) involved in pharmaceutical coverage decisions and/or CPG development. The interview scheme focused on the definition of patient preferences; how to integrate evidence on patient preferences in decision-making; and barriers and facilitators. RESULTS: Respondents mentioned various barriers and facilitators for integration, of conceptual, normative, procedural, methodological and practical nature. There is also variety in the terms and definitions used for preferences, complicating searching and synthesising evidence. It is not clear how to integrate evidence on patient preferences in different decision contexts, and what weight preferences should have in relation to other decision criteria. CONCLUSIONS: This study revealed important issues that need guidance when integrating evidence on patient preferences in healthcare policy decisions. PMID- 26563631 TI - Explaining inequalities in Health Care Utilization among Turkish adults: Findings from Health Survey 2008. AB - BACKGROUND: Turkish health system showed major improvements in health outcomes since initiation of the Health Transition Programme (HTP) in 2003, however little is known regarding income-related inequalities in health care use. The aim of this study was to assess horizontal inequities in health care use in Turkey. METHODS: We used the data from Turkish Health Survey 2008 with 14,655 respondents. We calculated concentration index (C) and horizontal inequity index (HI) to measure the socioeconomic inequalities in utilization of general practitioner (GP) care, specialist care, inpatient care, dental care and emergency care. Contributions of each factor to the observed inequality in health care utilization were assessed through decomposition method. RESULTS: There was a significant pro-rich inequality in specialist care and oral health care utilization among individuals as indicated by positive values of HI (=0.1149) and HI (=0.1137), respectively. However, the poor were more likely to utilize emergency care (HI=-0.0461) and inpatient care (HI=-0.0731). GP care was also slightly pro-poor distributed (HI=-0.0042). CONCLUSION: Pro-poor income-related inequalities in health care use were largely explained by greater health care need among low income groups, while non-need factors were the main determinants for pro-rich utilization (education, residence area). Inequalities in dental and specialist care linked to low income, low education level and rural areas should be given priority by decision makers to reduce the negative impact of utilization on health. Our results provide some evidence of inequity in 2008, after the introduction of HTP and provide a baseline against which the effects of the new reforms can be assessed. PMID- 26563632 TI - Valuing technology: A qualitative interview study with physicians about insulin pump therapy for children with type 1 diabetes. AB - Insulin pumps for children with type 1 diabetes have been broadly adopted despite equivocal evidence about comparative effectiveness. To understand why and inform policy related to public funding for new technologies, we explored how physicians interpret the value of pumps. We conducted open-ended, semi-structured interviews with 16 physicians from a pediatric diabetes network in Ontario, Canada, and analyzed the data using interpretive description. Respondents recognized that pumps fell short of expectations because they required hard work, as well as family and school support. Yet, pumps were valued for their status as new technologies and as a promising step in developing future technology. In addition, they were valued for their role within a therapeutic relationship, given the context of chronic childhood disease. These findings identify the types of beliefs that influence the adoption and diffusion of technologies. Some beliefs bear on hopes for new technology that may inappropriately hasten adoption, creating excess cost with little benefit. On the other hand, some beliefs identify potential benefits that are not captured in effectiveness studies, but may warrant consideration in resource allocation decisions. Still others suggest the need for remediation, such as those bearing on disparity in pump use by socioeconomic status. Understanding how technologies are valued can help stakeholders decide how to address such beliefs and expectations in funding decisions and implementation protocols. PMID- 26563633 TI - Health workforce governance in Europe: Where are we going? PMID- 26563634 TI - Well-Steered Charge-Carrier Transfer in 3D Branched CuxO/ZnO@Au Heterostructures for Efficient Photocatalytic Hydrogen Evolution. AB - Multi-component hetero-nanostructures exhibit multifunctional properties or synergistic performance and are thus considered as attractive materials for energy conversion applications. There is a long-standing demand to construct more sophisticated heterostructures for steering charge-carrier flow in semiconductor systems. Herein we fabricate a large-scale quantity of three-dimensional (3D) branched CuxO/ZnO@Au heterostructure consisting of CuO nanowires (NWs) and grafted ZnO nanodisks (NDs) decorated with Au nanoparticles via sequential hierarchical assemblies. This treelike hetero-nanostructure ensures well-steered transfer of photogenerated electrons to the exposed ZnO NDs, while holes to the CuO backbone NWs with concerted efforts from multi-node p-n junctions, polar ZnO facets, and Au plasmon, resulting in the significantly enhanced photocatalytic hydrogen evolution performance. PMID- 26563635 TI - Metabonomic diagnosis of bladder cancer: what are the advantages and considerations? PMID- 26563636 TI - Understanding psychological traumatic birth experiences: A literature review. AB - BACKGROUND: Traumatic birth experiences can cause postnatal mental health disturbance, fear of childbirth in subsequent pregnancies and disruption to mother-infant bonding, leading to impaired child development. Some women may develop postnatal Post Traumatic Stress Disorder, which is a particularly undesirable outcome. This paper aimed to gain a better understanding of factors contributing to birth trauma, and the efficacy of interventions that exist in the literature. METHODS: A literature search was undertaken in April 2015. Articles were limited to systematic reviews or original research of either high to moderate scientific quality. A total of 21 articles were included in this literature review. FINDINGS: Women with previous mental health disorders were more prone to experiencing birth as a traumatic event. Other risk factors included obstetric emergencies and neonatal complications. Poor Quality of Provider Interactions was identified as a major risk factor for experiencing birth trauma. Evidence is inconclusive on the best treatment for Post Traumatic Stress Disorder; however midwifery-led antenatal and postnatal interventions, such as early identification of risk factors for birth trauma and postnatal counselling showed benefit. CONCLUSION: Risk factors for birth trauma need to be addressed prior to birth. Consideration needs to be taken regarding quality provider interactions and education for maternity care providers on the value of positive interactions with women. Further research is required into the benefits of early identification of risk factors for birth trauma, improving Quality of Provider Interactions and how midwifery-led interventions and continuity of midwifery carer models could help reduce the number of women experiencing birth trauma. PMID- 26563637 TI - Midwifery capacity building in Papua New Guinea: Key achievements and ways forward. AB - BACKGROUND: Papua New Guinea has some of the poorest health outcomes in the Asia Pacific region. Maternal mortality is unacceptably high and there is a severe midwifery shortage requiring a quadrupling of the workforce. AIM: This paper outlines the findings of an evaluation of the Maternal Child Health Initiative (MCHI) (2012-2013) to determine key factors contributing to maternal health workforce strengthening. METHOD: A descriptive mixed methods study was undertaken. Data were gathered through interviews, focus group discussions and surveys with clinicians, midwifery students and staff from nursing and midwifery schools and National Department of Health staff. Documentation from stakeholder meetings and regular site reports were reviewed. Each data set was analysed separately and meta-inferences were drawn across all data. FINDINGS: Learning opportunities were found to have increased for midwifery educators and improvements were described in midwifery educators teaching capacity and student clinical education experience. There was an increase in the number of midwifery graduates and improvements were noted in the working environment and skills of clinical staff. Education challenges were described including the lack of clinical preceptoring and limited continuing education for clinical educators. Participants recommended increasing clinical education hours and extending the length of the midwifery program. Ongoing efforts to accredit the midwifery curricula and regulate midwifery graduates were noted. CONCLUSION: The MCHI has contributed to strengthening the midwifery workforce nationally. However, scaling up and sustaining these achievements requires leadership and funding commitments from the midwifery schools and government alongside the accreditation of midwifery curricula and regulation of new graduates. PMID- 26563638 TI - The perspectives of obese women receiving antenatal care: A qualitative study of women's experiences. AB - BACKGROUND: The prevalence of overweight and obesity is increasing amongst women of child bearing age. Maternal obesity has implications for both mother and baby including increased health risks from gestational hypertensive disorders, caesarean section and stillbirth. Despite the increasing prevalence of maternal obesity little is known of the experiences of these women within the health care system. The aim of this research was to investigate the perspectives of pregnant women with a body mass index (BMI) of >=30kg/m(2) receiving antenatal care. METHODS: A qualitative study using individual interviews was undertaken. Sixteen pregnant women with a BMI >=30kg/m(2) participated. Interviews were audio recorded, transcribed, cross checked for consistency and then entered into a word processing document for analysis. Data was analysed using Interpretative Phenomenological Analysis. In any phenomenological study the researcher's objective is to elicit the participant's views on their lived experiences. FINDINGS: Four major themes emerged: (1) obese during pregnancy as part of a long history of obesity; (2) lack of knowledge of the key complications of obesity for both mother and child; (3) communication about weight and gestational weight gain can be conflicting, confusing and judgmental; (4) most women are motivated to eat well during pregnancy and want help to do so. CONCLUSION: Specialist lifestyle interventions for obese women should be a priority in antenatal care. Extra support is required to assist obese women in pregnancy achieve recommended nutritional and weight goals. Health professionals should approach the issue of maternal obesity in an informative but non-judgmental way. PMID- 26563639 TI - The structure and organisation of home-based postnatal care in public hospitals in Victoria, Australia: A cross-sectional survey. AB - BACKGROUND: There is limited evidence regarding the provision of home-based postnatal care, resulting in a weak evidence-base for policy formulation and the further development of home-based postnatal care services. AIM: To explore the structure and organisation of public hospital home-based postnatal care in Victoria, Australia. METHODS: An online survey including mostly closed-ended questions was sent to representatives of all public maternity providers in July 2011. FINDINGS: The response rate of 87% (67/77) included rural (70%; n=47), regional (15%; n=10) and metropolitan (15%; n=10) services. The majority (96%, 64/67) provided home-based postnatal care. The median number of visits for primiparous women was two and for multiparous women, one. The main reason for no visit was the woman declining. Two-thirds of services attempted to provide some continuity of carer for home-based postnatal care. Routine maternal and infant observations were broadly consistent across the services, and various systems were in place to protect the safety of staff members during home visits. Few services had a dedicated home-based postnatal care coordinator. DISCUSSION AND CONCLUSION: This study demonstrates that the majority of women receive at least one home-based postnatal visit, and that service provision on the whole is similar across the state. Further work should explore the optimum number and timing of visits, what components of care are most valued by women, and what model best ensures the timely detection and prevention of postpartum complications, be they psychological or physiological. PMID- 26563640 TI - Source apportionment of emissions from light-duty gasoline vehicles and other sources in the United States for ozone and particulate matter. AB - Federal Tier 3 motor vehicle emission and fuel sulfur standards have been promulgated in the United States to help attain air quality standards for ozone and PM2.5 (particulate matter with an aerodynamic diameter <2.5 MUm). The authors modeled a standard similar to Tier 3 (a hypothetical nationwide implementation of the California Low Emission Vehicle [LEV] III standards) and prior Tier 2 standards for on-road gasoline-fueled light-duty vehicles (gLDVs) to assess incremental air quality benefits in the United States (U.S.) and the relative contributions of gLDVs and other major source categories to ozone and PM2.5 in 2030. Strengthening Tier 2 to a Tier 3-like (LEV III) standard reduces the summertime monthly mean of daily maximum 8-hr average (MDA8) ozone in the eastern U.S. by up to 1.5 ppb (or 2%) and the maximum MDA8 ozone by up to 3.4 ppb (or 3%). Reducing gasoline sulfur content from 30 to 10 ppm is responsible for up to 0.3 ppb of the improvement in the monthly mean ozone and up to 0.8 ppb of the improvement in maximum ozone. Across four major urban areas-Atlanta, Detroit, Philadelphia, and St. Louis-gLDV contributions range from 5% to 9% and 3% to 6% of the summertime mean MDA8 ozone under Tier 2 and Tier 3, respectively, and from 7% to 11% and 3% to 7% of the maximum MDA8 ozone under Tier 2 and Tier 3, respectively. Monthly mean 24-hr PM2.5 decreases by up to 0.5 MUg/m(3) (or 3%) in the eastern U.S. from Tier 2 to Tier 3, with about 0.1 MUg/m(3) of the reduction due to the lower gasoline sulfur content. At the four urban areas under the Tier 3 program, gLDV emissions contribute 3.4-5.0% and 1.7-2.4% of the winter and summer mean 24-hr PM2.5, respectively, and 3.8-4.6% and 1.5-2.0% of the mean 24 hr PM2.5 on days with elevated PM2.5 in winter and summer, respectively. IMPLICATIONS: Following U.S. Tier 3 emissions and fuel sulfur standards for gasoline-fueled passenger cars and light trucks, these vehicles are expected to contribute less than 6% of the summertime mean daily maximum 8-hr ozone and less than 7% and 4% of the winter and summer mean 24-hr PM2.5 in the eastern U.S. in 2030. On days with elevated ozone or PM2.5 at four major urban areas, these vehicles contribute less than 7% of ozone and less than 5% of PM2.5, with sources outside North America and U.S. area source emissions constituting some of the main contributors to ozone and PM2.5, respectively. PMID- 26563641 TI - Candida infection in the intensive care unit: A study of antifungal susceptibility pattern of Candida species in Milad hospital, Tehran, Iran. AB - OBJECTIVE: The occurrence of Candida infections has improved during the past two decades as a result of increase in the number of immunocompromised patients. In this study the antifungal susceptibility patterns of Candida species isolated from sterile body sites of patients admitted in Milad Intensive Care Unit (ICU) during 6 months were determined. METHODS: Candidal isolates were obtained from 50 patients admitted in Milad ICUs from April to September 2013. Identification of the isolates was performed by using morphological and polymerase chain reaction assay. Resistance to the antifungal agents containing caspofungin, posoconazole, voriconazole and amphotericin B was determined using E-test method. RESULTS: Out of 67 Candida isolates 47.8% were Candida glabrata, 28.3% were C. albicans, 7.5% were C. tropicalis, 7% were C. guilliermondii, 3% were C. krusei and 2% were C. dubliniensis. C. glabrata was the least susceptible species, with 9.4% of the isolates resistant to amphotericin B and 6.3% resistant to posoconazole and voriconazole. No resistance to caspofungin was observed among C. glabrata isolates. One of the C. krusei isolates was resistant to amphotericin B while no resistance to voriconazole, caspofungin and posoconazole was detected among C. krusei strains. Increase in the prevalence of antifungal-resistant non-C. albicans species in recent years has become a problematic event amongst clinicians caring for ICU patients. C. glabrata as the most common species isolated from ICU patients in this study indicated higher levels of antifungal resistance in comparison with other species. This observation accentuates the importance of managing preventive treatments to avoid development of resistance to the current antifungal drugs. PMID- 26563642 TI - The expression of PLP/DM-20 mRNA is restricted to the oligodendrocyte-lineage cells in the adult rat spinal cord. AB - Proteolipid protein (PLP) is the major component of myelin; its gene encodes two major splicing variants: PLP and DM-20. Compared with PLP, DM-20 lacks the amino acids encoded by exon IIIb. The expression of PLP/DM-20 in cells outside the oligodendrocyte-lineage is unclear. To address this issue, we analyzed the detailed expression pattern of PLP/DM-20 mRNA in the adult rat spinal cord by in situ hybridization (ISH) with a cRNA probe complementary to DM-20 mRNA, which has been used to detect both PLP and DM-20 both mRNA. ISH did not label the cells expressing NeuN nor glial fibrillary acidic protein but detected those expressing Olig2, indicating that PLP/DM-20 mRNA are expressed only in oligodendrocyte lineage cells. This cell population was expected to contain NG2-expressing oligodendrocyte precursor cells (OPCs), because some exhibited the expression of glutathione S-transferase pi isoform in the nucleus. A recent publication showed that OPCs express PLP but not DM-20 mRNA. However, no OPCs were detected. We performed ISH with a cRNA probe that specifically recognizes PLP mRNA to successfully detect some OPCs. Additionally, OPCs were detected by ISH with a cRNA probe complementary to DM-20 mRNA that was digested via alkaline hydrolysis prior to ISH. These findings collectively demonstrate that PLP and DM-20 mRNA expression is restricted to oligodendrocyte-lineage cells, and imply that the undigested cRNA probe complementary to the full-length DM-20 mRNA sequence only recognizes DM-20 mRNA and not the PLP counterpart when applied to ISH without denaturation/digestion methods. PMID- 26563644 TI - Kinematics and energetics of swimming performance during acute warming in brown trout Salmo trutta. AB - This study examined how acute warming of water temperature affects the mechanical efficiency of swimming and aerobic capabilities of the brown trout Salmo trutta. Swimming efficiency was assessed using the relationship between swimming kinematics and forward speed (U), which is thought to converge upon an optimum range of a dimensionless parameter, the Strouhal number (St ). Swim-tunnel intermittent stopped-flow respirometry was used to record kinematics and measure oxygen consumption (MO2) of S. trutta during warming and swimming challenges. Salmo trutta maintained St between 0.2 and 0.3 at any given U over a range of temperatures, irrespective of body size. The maintenance of St within the range for maximum efficiency for oscillatory propulsion was achieved through an increase in tail-beat frequency (ftail) and a decrease in tail-beat amplitude (A) as temperature increased. Maintenance of efficient steady-state swimming was fuelled by aerobic metabolism, which increased as temperature increased up to 18 degrees C but declined above this temperature, decreasing the apparent metabolic scope. As St was maintained over the full range of temperatures whilst metabolic scope was not, the results may suggest energetic trade-offs at any given U at temperatures above thermal optima. PMID- 26563643 TI - Validating the Implementation Climate Scale (ICS) in child welfare organizations. AB - There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. PMID- 26563645 TI - Cancer immunotherapy--Converting immune failure to clinical response. PMID- 26563647 TI - Is a synthetic augmentation in medial open wedge high tibial osteotomies superior to no augmentation in terms of bone-healing? AB - INTRODUCTION: Medial open-wedge high tibial osteotomy (MOWHTO) is an established method to treat unicompartimental osteoarthritis of the knee joint. However, augmentation of the created tibial gap after osteotomy is controversially discussed. METHODS: We performed a prospective investigation of 49 consecutive cases of MOWHTO at our department. Patients were divided into two groups: group A consisted of 19 patients while group B consisted of 30 patients. In group A, the augmentation of the opening gap after osteotomy was filled with a synthetic bone graft, whereas group B received no augmentation. As an indicator for bone healing we investigated the non-union rate in our study population and compared the non union-rate between the two groups. RESULTS: The non-union rate was 28% in group A (five of 19 patients had to undergo revision) which received synthetic augmentation, while it was 3.3% in group B (one of 30 patients had to undergo revision) which received no augmentation. The difference between the groups was statistically significant (p-value 0.027). CONCLUSIONS: With regard to bone healing after MOWHTO, synthetic augmentation was not superior to no augmentation in terms of non-union rates after surgery. In fact, we registered a significantly higher rate of non-union after augmentation with synthetic bone graft. LEVEL OF EVIDENCE: III. PMID- 26563648 TI - How to conduct systematic reviews more expeditiously? AB - Healthcare consumers, researchers, patients and policy makers increasingly use systematic reviews (SRs) to aid their decision-making process. However, the conduct of SRs can be a time-consuming and resource-intensive task. Often, clinical practice guideline developers or other decision-makers need to make informed decisions in a timely fashion (e.g. outbreaks of infection, hospital based health technology assessments). Possible approaches to address the issue of timeliness in the production of SRs are to (a) implement process parallelisation, (b) adapt and apply innovative technologies, and/or (c) modify SR processes (e.g. study eligibility criteria, search sources, data extraction or quality assessment). Highly parallelised systematic reviewing requires substantial resources to support a team of experienced information specialists, reviewers and methodologists working alongside with clinical content experts to minimise the time for completing individual review steps while maximising the parallel progression of multiple steps. Effective coordination and management within the team and across external stakeholders are essential elements of this process. Emerging innovative technologies have a great potential for reducing workload and improving efficiency of SR production. The most promising areas of application would be to allow automation of specific SR tasks, in particular if these tasks are time consuming and resource intensive (e.g. language translation, study selection, data extraction). Modification of SR processes involves restricting, truncating and/or bypassing one or more SR steps, which may risk introducing bias to the review findings. Although the growing experiences in producing various types of rapid reviews (RR) and the accumulation of empirical studies exploring potential bias associated with specific SR tasks have contributed to the methodological development for expediting SR production, there is still a dearth of research examining the actual impact of methodological modifications and comparing the findings between RRs and SRs. This evidence would help to inform as to which SR tasks can be accelerated or truncated and to what degree, while maintaining the validity of review findings. Timely delivered SRs can be of value in informing healthcare decisions and recommendations, especially when there is practical urgency and there is no other relevant synthesised evidence. PMID- 26563649 TI - Effect of Obesity on Complication Rate After Elbow Arthroscopy in a Medicare Population. AB - PURPOSE: To use a national insurance database to explore the association of obesity with the incidence of complications after elbow arthroscopy in a Medicare population. METHODS: Using Current Procedural Terminology (CPT) and International Classification of Diseases, 9th Revision (ICD-9) procedure codes, we queried the PearlDiver database for patients undergoing elbow arthroscopy. Patients were divided into obese (body mass index [BMI] >30) and nonobese (BMI <30) cohorts using ICD-9 codes for BMI and obesity. Nonobese patients were matched to obese patients based on age, sex, tobacco use, diabetes, and rheumatoid arthritis. Postoperative complications were assessed with ICD-9 and Current Procedural Terminology codes, including infection, nerve injury, stiffness, and medical complications. RESULTS: A total of 2,785 Medicare patients who underwent elbow arthroscopy were identified from 2005 to 2012; 628 patients (22.5%) were coded as obese or morbidly obese, and 628 matched nonobese patients formed the control group. There were no differences between the obese patients and matched control nonobese patients regarding type of elbow arthroscopy, previous elbow fracture or previous elbow arthroscopy. Obese patients had greater rates of all assessed complications, including infection (odds ratio [OR] 2.8, P = .037), nerve injury (OR 5.4, P = .001), stiffness (OR 1.9, P = .016) and medical complications (OR 6.9, P < .0001). CONCLUSIONS: Obesity is associated with significantly increased rates of all assessed complications after elbow arthroscopy in a Medicare population, including infection, nerve injury, stiffness, and medical complications. LEVEL OF EVIDENCE: Therapeutic Level III, case-control study. PMID- 26563646 TI - CAR T-cell immunotherapy: The path from the by-road to the freeway? AB - Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit. PMID- 26563650 TI - Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. AB - BACKGROUND: Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. RESULTS: The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. CONCLUSION: The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer. PMID- 26563651 TI - Targeting anti-apoptotic Bcl2 proteins with scyllatoxin-based BH3 domain mimetics. AB - BH3 domain mimetics based on the small protein scyllatoxin (ScTx) were designed to target the anti-apoptotic protein Bcl2 in vitro. Intrinsically disordered ScTx variants were found to bind Bcl2 with nanomolar affinity, indicating that an induced fit binding mechanism is required for favorable BH3 : Bcl2 interaction. PMID- 26563652 TI - Development and characterization of human monoclonal antibodies that neutralize multiple TGFbeta isoforms. AB - Transforming growth factor (TGF)beta levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFbeta1, 2, and 3. As multiple TGFbeta isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFbeta isoforms. Fully human antibody phage display libraries were used to discover a number of antibodies that bind and neutralize various combinations of TGFbeta1, 2 or 3. The primary panning did not yield any uniformly potent pan-isoform neutralizing antibodies; therefore, an antibody that displayed potent TGFbeta 1, 2 inhibition, but more modest affinity versus TGFbeta3, was affinity matured by shuffling with a light chain sub-library and further screening. This process yielded a high affinity pan-isoform neutralizing clone. Antibodies were analyzed and compared by binding affinity, as well as receptor and epitope competition by surface plasmon resonance methods. The antibodies were also shown to neutralize TGFbeta effects in vitro in 3 assays: 1) interleukin (IL)-4 induced HT-2 cell proliferation; 2) TGFbeta-mediated IL-11 release by A549 cells; and 3) decreasing SMAD2 phosphorylation in Detroit 562 cells. The antibodies' potency in these in vitro assays correlated well with their isoform-specific affinities. Furthermore, the ability of the affinity-matured clone to decrease tumor burden in a Detroit 562 xenograft study was superior to that of the parent clone. This affinity-matured antibody acts as a very potent inhibitor of all 3 main isoforms of TGFbeta and may have utility for therapeutic intervention in human disease. PMID- 26563653 TI - Which colours are seen by the patient during cataract surgery? Results of an intraoperative interview. AB - PURPOSE: To discover what cataract patients see during phacoemulsification and if these light phenomena influence their anxiety levels during surgery. METHODS: In all, 200 patients were interviewed intraoperatively at the Eye Hospital, Petrisberg, Trier, Germany. The quality of the visual experiences was described and if these were pleasant, neutral or unpleasant. Systemic sedation was noted. RESULTS: Among 200 patients (209 eyes): 88 were men (91 eyes; 44%) and 112 were women (118 eyes; 56%). Median age (years): men (71), women (70). Mean operating time was 8 min. 49/209 (23%) were not anxious before and during surgery. 110/209 (52%) were more anxious before than during surgery, 50/209 (24%) were still anxious during surgery, 27/209 (13%) got sedation with midazolam (1-5 mg). Colours in descending order seen: blue, red, pink, yellow, green, purple, turquois, and orange. The most dominant colour combination was red/blue. Structures were seen by 162/209 (78%). Most (61%) intraoperative visual experiences were pleasant, 38% were neutral, and 1% found them transiently unpleasant. Three patients felt blinded by the light of the operating microscope. CONCLUSIONS: The experience of colours and other light phenomena was pleasant for most patients during phacoemulsification under topical anaesthesia. They occur spontaneously when the patient is fixating on the operating light. They are not dependent on the individual or environment. Sedation only in 13%. Direct questioning for visual sensations by the operating surgeon may lead to less need for sedation and lead to less side effects for elderly and multimorbidity people postoperatively. The surgeon can use this knowledge to reassure patients during surgery. PMID- 26563654 TI - Reply to: 'TLP: a premature concept'. PMID- 26563655 TI - TLP: a premature concept. PMID- 26563656 TI - A 12-year review on the aetiology and surgical outcomes of paediatric rhegmatogenous retinal detachments in Hong Kong. AB - PURPOSE: To evaluate the aetiology, clinical features, and surgical outcomes of paediatric rhegmatogenous retinal detachments (RRD) in Hong Kong.Patients and methodsThis is a retrospective consecutive case series of all patients aged 18 or under who underwent primary retinal detachment repair in the Hong Kong Eye Hospital from January 2000 to December 2012.ResultsForty-nine eyes of 47 patients were included. The mean age was 14, and the mean follow-up duration was 6.2 years. The most common aetiology for RRD was idiopathic (28.6%), followed by high myopia (24.5%), atopic dermatitis (AD) (18.4%), congenital and developmental abnormalities (16.3%), trauma (8.2%), and intraocular inflammation (4.1%). The mean preoperative visual acuity was LogMAR 1.0+/-0.8 (Snellen equivalent 6/60). The primary anatomical success rate in this series was 65.3%, and the final anatomical success rate was 85.7%. The mean postoperative visual acuity was LogMAR 0.9+/-1.2 (Snellen equivalent 6/48). Patients with congenital and developmental abnormalities or AD had worse anatomical and functional outcomes than patients who had no predisposing factor or high myopia. CONCLUSIONS: The primary and overall anatomical success rates in our series were comparable with existing literature. High myopia is the most commonly identifiable risk factor in Hong Kong and AD is associated with a higher re-detachment rates and a poor visual outcome. PMID- 26563657 TI - Addressing the 'forgotten art of fundoscopy': evaluation of a novel teaching ophthalmoscope. AB - BACKGROUND: Direct ophthalmoscopy is an essential skill that students struggle to learn. A novel 'teaching ophthalmoscope' has been developed that allows a third person to observe the user's view of the fundus. OBJECTIVES: To evaluate the potential use of this device as an aid to learning, and as a tool for objective assessment of competence. METHODS: Participants were randomised to be taught fundoscopy either with a conventional direct ophthalmoscope (control) or with the teaching device (intervention). Following this teaching session, participant competence was assessed within two separate objective structured clinical examination (OSCE) stations: the first with the conventional ophthalmoscope and the second with the teaching device. Each station was marked by two independent masked examiners. Students were also asked to rate their own confidence in fundoscopy on a scale of 1-10. Scores of competence and confidence were compared between groups. The agreement between examiners was used as a marker for inter rater reliability and compared between the two OSCE stations. RESULTS: Fifty-five medical students participated. The intervention group scored significantly better than controls on station 2 (19.8 vs 17.6; P=0.01). They reported significantly greater levels of confidence in fundoscopy (7.3 vs 4.9; P<0.001). Independent examiner scores showed significantly improved agreement when using the teaching device during assessment of competence, compared to the conventional ophthalmoscope (r=0.90 vs 0.67; P<0.001). CONCLUSION: The teaching ophthalmoscope is associated with improved confidence and objective measures of competence, when compared with a conventional direct ophthalmoscope. Used to assess competence, the device offers greater reliability than the current standard. PMID- 26563658 TI - Evaluation of ocular pulse amplitude and choroidal thickness in diabetic macular edema. AB - PURPOSE: The aim of this study is to evaluate the ocular pulse amplitude (OPA) and choroidal thickness (CT) measurements in patients with diabetic macular edema (DME) and healthy subjects. METHODS: A total of 34 patients (12 male and 22 female) who had type 2 diabetes mellitus with DME and 34 sex-matched healthy subjects (13 male and 21 female) were included in this prospective study. The intraocular pressure (IOP) and OPA were measured with Dynamic contour tonometer (Pascal DCT, Switzerland). The subfoveal CT was measured using the Cirrus HD-OCT (Carl Zeiss Meditec). The CT at 1500 MUm and 3000 MUm nasal and temporal to the central fovea was also measured. RESULTS: The mean IOP values were 18.4+/-3.5 and 17.1+/-2.1 mm Hg in DME patients and healthy controls, respectively (P= 0.091). The mean OPA values in patients with DME (2.58+/-0.96) and controls (3.52+/-1.03) were statistically different (P<0.001). The mean subfoveal CT value was 273.5+/ 30.2 MUm in the eyes with DME and 321.4+/-36.5 MUm in the control group (P< 0.001). In both groups, linear regression analysis showed no significant association between OPA and CT measurements. The IOP showed a significantly positive correlation with OPA in both DME (P=0.002, r=0.526) and controls (P=0.004, r=0.483). CONCLUSIONS: The current study suggests that both pulsatile choroidal blood flow and CT are decreased in patients with DME. PMID- 26563659 TI - Vision, eye disease, and art: 2015 Keeler Lecture. AB - The purpose of this study was to examine normal vision and eye disease in relation to art. Ophthalmology cannot explain art, but vision is a tool for artists and its normal and abnormal characteristics may influence what an artist can do. The retina codes for contrast, and the impact of this is evident throughout art history from Asian brush painting, to Renaissance chiaroscuro, to Op Art. Art exists, and can portray day or night, only because of the way retina adjusts to light. Color processing is complex, but artists have exploited it to create shimmer (Seurat, Op Art), or to disconnect color from form (fauvists, expressionists, Andy Warhol). It is hazardous to diagnose eye disease from an artist's work, because artists have license to create as they wish. El Greco was not astigmatic; Monet was not myopic; Turner did not have cataracts. But when eye disease is documented, the effects can be analyzed. Color-blind artists limit their palette to ambers and blues, and avoid greens. Dense brown cataracts destroy color distinctions, and Monet's late canvases (before surgery) showed strange and intense uses of color. Degas had failing vision for 40 years, and his pastels grew coarser and coarser. He may have continued working because his blurred vision smoothed over the rough work. This paper can barely touch upon the complexity of either vision or art. However, it demonstrates some ways in which understanding vision and eye disease give insight into art, and thereby an appreciation of both art and ophthalmology. PMID- 26563660 TI - Diurnal intraocular pressure fluctuation and its risk factors in angle-closure and open-angle glaucoma. AB - PURPOSE: To evaluate intraocular pressure (IOP) fluctuation during office hours and its predictive factors in untreated primary angle-closure suspects (PACS); post-iridotomy primary angle closure (PAC) and primary angle-closure glaucoma (PACG) eyes with or without IOP-lowering medication(s) as appropriate and medically treated primary open-angle glaucoma (POAG) eyes. METHODS: One-hundred seventeen eyes (29 PACS, 30 PAC, 28 PACG, and 30 POAG) of 117 patients were included in this cross-sectional study. The subjects underwent hourly IOP measurements with Goldmann tonometer from 0800 to 1700 hours. Subjects with PAC and PACG had laser peripheral iridotomy at least 2 weeks prior to the inclusion. SD of office-hour IOP readings was the main outcome measure. RESULTS: IOP fluctuation differed between the groups (P=0.01; Kruskal-Wallis Test). Post hoc Mann-Whitney U-tests showed significantly less IOP fluctuation in PACS compared with PACG (P<0.01). Peak office-hour IOP was observed in the morning in untreated subjects and in the early afternoon in treated subjects. A stepwise linear regression model identified the presence of peripheral anterior synechiae (PAS), thickness of lens, large vertical cup-to-disc ratio (VCDR), and PAC category as significant predictive factors associated with office-hour IOP fluctuation. CONCLUSIONS: Diurnal IOP fluctuation in asymptomatic PACSs was less than that in treated PACG subjects and was at least comparable to that in treated PAC and POAG subjects. The greater the amount of PAS, the thicker the lens, the larger the VCDR, the greater was the IOP fluctuation during office hours. PMID- 26563661 TI - Why rods and cones? AB - Under twenty-first-century metropolitan conditions, almost all of our vision is mediated by cones and the photopic system, yet cones make up barely 5% of our retinal photoreceptors. This paper looks at reasons why we additionally possess rods and a scotopic system, and asks why rods comprise 95% of our retinal photoreceptors. It considers the ability of rods to reliably signal the arrival of individual photons of light, as well as the ability of the retina to process these single-photon signals, and it discusses the advantages that accrue. Drawbacks in the arrangement, including the very slow dark adaptation of scotopic vision, are also considered. Finally, the timing of the evolution of cone and rod photoreceptors, the retina, and the camera-style eye is summarised. PMID- 26563662 TI - [Intravenous thrombolysis in ischemic stroke: Therapeutic perspectives]. AB - New therapeutic strategies are under evaluation to improve the treatment of acute ischemic stroke (AIS). Approaches combining intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) and antithrombotic agents are currently evaluated. The combination of IV rt-PA and aspirin showed a high rate of intracranial hemorrhage whereas the association of rt-PA and eptifibatide seems more promising. The results of recent studies evaluating the administration of eptifibatide or argatroban in conjunction with conventional IV thrombolysis with rt-PA are expected to clarify the safety and efficacy of these treatments. More fibrin-specific plasminogen activators, tenecteplase and desmoteplase, are also investigated. These fibrinolytic agents showed a favorable safety profile but their efficacy in AIS remains uncertain. While phase III studies, DIAS-3 and DIAS-4, evaluating IV desmoteplase up to nine hours after stroke onset did not meet the primary endpoint, the results of studies comparing IV tenecteplase and IV rt-PA are expected. PMID- 26563663 TI - [Is Parkinson's disease a prion disease?]. AB - The accumulation of a specific protein in aggregated form is a common phenomenon in human neurodegenerative diseases. In Parkinson's disease, this protein is alpha-synuclein which is a neuronal protein of 143 amino acids. With a monomeric conformation in solution, it also has a natural capacity to aggregate into amyloid structures (dimers, oligomers, fibrils and Lewy bodies or neurites). It therefore fulfils the characteristics of a prion protein (different conformations, seeding and spreading). In vitro and in vivo experimental evidence in transgenic and wild animals indicates a prion-like propagation of Parkinson's disease. The sequential and predictive distribution of alpha-synuclein demonstrated by Braak et al. and its correlation with non-motor signs are consistent with the prion-like progression. Although the triggering factor causing the misfolding and aggregation of the target protein is unknown, Parkinson's disease is a highly relevant model for the study of these mechanisms and also to test specific treatments targeting the assemblies of alpha-synuclein and propagation from pre-motor phase of the disease. Despite this prion-like progression, there is currently no argument indicating a risk of human transmission of Parkinson's disease. PMID- 26563664 TI - [Creation and normalisation of a verbal episodic memory task in elderly adults: "GERIA-12"]. AB - INTRODUCTION: Early damage to episodic memory encoding and consolidation processes has been demonstrated in dementia of the Alzheimer type. However, in the domain of verbal episodic memory assessment, there are few diagnostic tools adapted to the old and oldest old as far as ease of administration and accuracy of normative data are concerned. Classic tasks are either too effortful (like the free recall/cued recall of 16 items), not sensitive enough (like the 5 words test), or insufficiently accurate for people above 70 years old in terms of normative data. AIM: The aim of this study was to develop a reduced task (in terms of number of items and number of trials) assessing verbal episodic memory in people aged between 70 and 89 years old. METHODS: The task (GERIA-12) used the same procedure as the RL/RI-16 task but the list comprised only 12 words and there were only 2 learning trials. In order to assess consolidation processes, we included 2 delayed recall trials, one after 20 minutes and the other after 24 hours. We also calculated indexes adapted from the Item-Specific Deficit Approach developed by Wright et al., which has the advantage of providing measures specific to encoding, consolidation and retrieval processes. Standardization was done with data from 220 people aged between 70 and 89 years old and belonging to 3 education levels. RESULTS: We obtained a significant effect of age and education level: scores decrease with age and increase with education. Norms have thus been calculated taking those two variables into consideration. Concerning the standardization, Barona method has been used for free recall scores while percentiles have been used for all other scores (total recall, free recall, encoding, consolidation and retrieval indexes). Normative data are also provided for intrusions and perseverations. CONCLUSION: This new task allows encoding, consolidation and retrieval processes assessment in older people and has the following advantages: the procedure is more suitable (ease and time of administration), there are accurate normative data for old and oldest old people, and there are normative data for two delayed recalls (at 20 minutes and at 24 hours). PMID- 26563665 TI - [An unusual revelation of miliary tuberculosis due to Mycobacterium bovis in two immunocompetent patients]. PMID- 26563666 TI - Association study of apolipoprotein E promoter polymorphism (-427 T/C) and Alzheimer's disease in a Tunisian population. AB - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an as yet poorly understood etiology. Both environmental and genetic factors have been implicated as predisposing factors. The apolipoprotein E (APOE) E4 allele is an established genetic susceptibility factor for AD for several populations including the Tunisian population. Polymorphism rs769446 (-427 T/C) at the promoter region of the APOE gene is postulated to affect the expression of the gene through differential binding of transcription factors. AIMS: This study aims at examining the APOE promoter polymorphism rs769446 for possible association with AD in a Tunisian population. METHODS: Using a case-control study design, a sample of 85 patients and 90 controls were investigated for association with the rs769446 polymorphism. RESULTS: No evidence of association was found in this population upon comparison between patients and healthy controls or upon stratification by APOE E4. CONCLUSIONS: Investigations of potential gene-gene and gene-environmental interactions for this polymorphism need to be further conducted. PMID- 26563667 TI - Triage practices in stroke units: Physicians' perceptions and ethical issues. AB - OBJECTIVE: We aimed to explore acute stroke admission decisions and to discuss ethical issues in triage practices in stroke units (SUs) in France. METHODS: In this study, 337 questionnaires were sent to physicians involved in acute admission to SUs in Ile-de-France (neurologists and physicians from emergency medical services). The questionnaires comprised questions about physicians' perceptions of the reasonable allocation of SU beds and admission criteria for patients in SU in clinical vignettes illustrating complex situations. RESULTS: In total, 162 questionnaires were fully completed. There were some discrepancies in perceptions and reporting practices between emergency physicians and neurologists concerning patient admission criteria. Triage choices were more frequently declared by emergency physicians than by neurologists and were related to the difficulty of obtaining a positive response for the admission of certain complex patients (particularly those with comorbidities). CONCLUSIONS: Despite recommendations stating that all patients with stroke should be admitted to SUs, this study has shown that triage practices exist in stroke admission decisions. The triage depends on the role and perceptions of each physician in acute stroke management. These decisions suggest reflections on the applicability of distributive justice theories and on ethical issues in triage practices in medicine. PMID- 26563669 TI - Long-term variability of exhaled nitric oxide measurements. PMID- 26563670 TI - The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial. AB - BACKGROUND: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS). OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 MUg or 2.5 MUg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma. METHODS: A phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 MUg budesonide or equivalent dose) and a pre-bronchodilator forced expiratory volume in 1 second (FEV1) >=60% and <=90% of predicted normal were randomized to 12 weeks of treatment with once-daily tiotropium Respimat 5 MUg or 2.5 MUg, or placebo Respimat, as add-on therapy to ICS. The primary endpoint was peak FEV1(0 3h) response. RESULTS: In total, 464 patients were randomized (61% female; mean age 43 years; mean baseline FEV1 78% of predicted normal). After 12 weeks, both tiotropium Respimat doses were superior to placebo (adjusted mean difference from placebo: 5 MUg, 128 mL; 2.5 MUg, 159 mL; both P < .001). Both doses of tiotropium Respimat were also superior to placebo with regard to the secondary endpoints of adjusted mean trough FEV1 and FEV1 area under the curve(0-3h) responses, and the other endpoints of morning and evening peak expiratory flow. Adverse events were comparable across the treatment groups. CONCLUSIONS: Once-daily tiotropium Respimat add-on therapy to low- to medium-dose ICS in adults with symptomatic asthma is an efficacious bronchodilator, and its safety and tolerability are comparable with those of placebo Respimat. PMID- 26563671 TI - Development of eosinophilic endomyocardial disease in a patient with episodic angioedema and eosinophilia. PMID- 26563668 TI - International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. PMID- 26563673 TI - Shrimp allergy: Gastrointestinal symptoms commonly occur in the absence of IgE sensitization. PMID- 26563672 TI - Behavioral Interventions to Improve Asthma Outcomes for Adolescents: A Systematic Review. AB - BACKGROUND: Factors at multiple ecological levels, including the child, family, home, medical care, and community, impact adolescent asthma outcomes. OBJECTIVE: This systematic review characterizes behavioral interventions at the child, family, home, medical system, and community level to improve asthma management among adolescents. METHODS: A systematic search of PubMed, SCOPUS, OVID, PsycINFO, CINAHL, and reference review databases was conducted from January 1, 2000, through August 10, 2014. Articles were included if the title or abstract included asthma AND intervention AND (education OR self-management OR behavioral OR technology OR trigger reduction), and the mean and/or median age of participants was between 11 and 16 years. We compared populations, intervention characteristics, study designs, outcomes, settings, and intervention levels across studies to evaluate behavioral interventions to improve asthma management for adolescents. RESULTS: Of 1230 articles identified and reviewed, 24 articles (21 unique studies) met inclusion criteria. Promising approaches to improving adherence to daily controller medications include objective monitoring of inhaled corticosteroid adherence with allergist and/or immunologist feedback on medication-taking behavior and school nurse directly observed therapy. Efficacy at increasing asthma self-management skills was demonstrated using group interactive learning in the school setting. This systematic review is not a meta analysis, thus limiting its quantitative assessment of studies. Publication bias may also limit our findings. CONCLUSIONS: Novel strategies to objectively increase controller medication adherence for adolescents include allergist and/or immunologist feedback and school nurse directly observed therapy. Schools, the most common setting across studies in this review, provide the opportunity for group interactive learning to improve asthma knowledge and self-management skills. PMID- 26563674 TI - The Immune Phenotype of Patients with CHARGE Syndrome. AB - BACKGROUND: Recurrent sinopulmonary infections are common in children with CHARGE (Coloboma, Heart disease, choanal Atresia, growth/mental Retardation, Genitourinary malformations, Ear abnormalities) syndrome, but no prospective studies on immune function have been conducted. OBJECTIVE: This study aims to examine and compare the immune phenotype of patients with CHARGE syndrome to those with 22q11.2 deletion and healthy controls. METHODS: A total of 21 patients attended a multidisciplinary CHARGE clinic. All patients had CHD7 mutational analysis performed. Patients with CHARGE syndrome had lymphocyte subsets, immunoglobulins (IgG, A, M), functional protein, and polysaccharide vaccine responses measured at initial evaluation. A total of 55 healthy controls were prospectively recruited, whereas 40 patients with 22q11.2 deletion were retrospectively identified through medical records. A separate analysis compared serial lymphocyte counts and ionized calcium levels between patients with CHARGE syndrome and those with 22q11.2 deletion in the first 72 months of life. RESULTS: Despite recurrent childhood ear and chest infections, only 2 children with CHARGE syndrome had an identifiable immune defect (reduced serum IgA). In contrast, T cell lymphopenia, low immunoglobulin levels, and specific antibody deficiency were noted in patients with 22q11.2 deletion. A greater proportion of patients with 22q11.2 deletion had persistent lymphopenia (57% vs 30%) and hypocalcemia (60% vs 37.5%) compared with patients with CHARGE syndrome in the first 72 months of life. CONCLUSIONS: Although phenotypic overlap exists between CHARGE and 22q11.2 deletion syndromes, no significant immune defects were detected in this cohort of patients with CHARGE syndrome at the time of testing. Lymphopenia and hypocalcemia occur in both conditions early in life, but is more pronounced in patients with 22q11.2 deletion. PMID- 26563675 TI - High adherence to hymenoptera venom subcutaneous immunotherapy over a 5-year follow-up: A real-life experience. PMID- 26563677 TI - Modal engineering of Surface Plasmons in apertured Au Nanoprisms. AB - Crystalline gold nanoprisms of sub-micrometric size sustain high order plasmon modes in the visible and near infrared range that open a new realm for plasmon modal design, integrated coplanar devices and logic gates. In this article, we explore the tailoring of the surface plasmon local density of states (SP-LDOS) by embedding a single defect, namely a small hole, carved in the platelet by focused ion beam (FIB). The change in the SP-LDOS of the hybrid structure is monitored by two-photon luminescence (TPL) microscopy. The dependency of the two-dimensional optical field intensity maps on the linear polarization of the tightly focused femtosecond laser beam reveals the conditions for which the hole defect significantly affects the initial modes. A detailed numerical analysis of the spectral characteristics of the SP-LDOS based on the Green dyadic method clearly indicates that the hole size and location can be exploited to tune or remove selected SP modes. PMID- 26563676 TI - Depression, Asthma, and Bronchodilator Response in a Nationwide Study of US Adults. AB - BACKGROUND: Little is known about the relation between 2 common comorbidities (depression and anxiety) and asthma or bronchodilator response (BDR). OBJECTIVE: To examine the association between depressive symptoms and asthma or BDR in US adults. METHODS: Cross-sectional study of 20,272 adults aged 20 to 79 years from the 2007-2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the 9-item Patient Health Questionnaire, and classified as none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a 9-item Patient Health Questionnaire score of 15 or more. Anxiety was defined as 5 or more days feeling anxious in the previous month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and 1 or more asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1356 participants with FEV1/forced vital capacity of less than 0.70 and/or FEV1 less than 70% of predicted. Logistic or linear regression was used for the multivariable analysis. RESULTS: Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 times higher odds of asthma than did those with minimal or no depressive symptoms (95% CI, 2.6-4.5; P < .01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI, 7.5% to -0.8%; P = .02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. CONCLUSIONS: Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma. PMID- 26563678 TI - Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses. AB - BACKGROUND: Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. OBJECTIVE: The aim was to study emotional reactions to pro-anorexia and anti-pro anorexia online content on YouTube using sentiment analysis. METHODS: Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader's activity as a video commentator, and uploader's physical location by country. RESULTS: The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. CONCLUSIONS: Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more positive feedback and comments than pro-anorexia videos. Thus, the anti-pro anorexia content provided a user-generated counterforce against pro-anorexia content on YouTube. Professionals working with young people should be aware of the social media dynamics and versatility of user-generated eating disorder content online. PMID- 26563679 TI - Electronic band-gap modified passive silicon optical modulator at telecommunications wavelengths. AB - The silicon optical modulator is considered to be the workhorse of a revolution in communications. In recent years, the capabilities of externally driven active silicon optical modulators have dramatically improved. Self-driven passive modulators, especially passive silicon modulators, possess advantages in compactness, integration, low-cost, etc. Constrained by a large indirect band-gap and sensitivity-related loss, the passive silicon optical modulator is scarce and has been not advancing, especially at telecommunications wavelengths. Here, a passive silicon optical modulator is fabricated by introducing an impurity band in the electronic band-gap, and its nonlinear optics and applications in the telecommunications-wavelength lasers are investigated. The saturable absorption properties at the wavelength of 1.55 MUm was measured and indicates that the sample is quite sensitive to light intensity and has negligible absorption loss. With a passive silicon modulator, pulsed lasers were constructed at wavelengths at 1.34 and 1.42 MUm. It is concluded that the sensitive self-driven passive silicon optical modulator is a viable candidate for photonics applications out to 2.5 MUm. PMID- 26563680 TI - Comorbid risks of deep vein thrombosis and pulmonary thromboembolism in patients with chronic pancreatitis: a nationwide cohort study. AB - ESSENTIALS: Risks of deep vein thrombosis (DVT) and pulmonary embolism (PE) in chronic pancreatitis (CP) are unclear. We conducted a nationwide cohort study to evaluate the risks of DVT and PE in CP patients. 17 778 patients with CP and 71 106 without CP were followed for 86 740 and 429 116 person-years, respectively. Patients with CP had a 2.95-fold increased rate of DVT and a 4.51-fold increased rate of PE. BACKGROUND: Studies on the association between chronic pancreatitis (CP) and cardiovascular diseases are scarce. We conducted a nationwide cohort study to evaluate the risks of deep vein thrombosis (DVT) and pulmonary embolism (PE) in CP patients. METHODS: Using the data from the Taiwan National Health Insurance Research Database, we randomly selected a non-CP cohort from insurants without a history of CP, and frequency-matched them at a ratio of 4 : 1 according to age, sex and index year with each patient newly diagnosed with CP between 2000 and 2010. The follow-up period ranged from the index date of new CP diagnosis to the diagnosis of DVT or PE, censoring, or the end of 2011. We used univariable and multivariable Cox proportional hazard regression models to determine the risks of DVT and PE. RESULTS: In total, 17 778 patients in the CP cohort (82.6% men; mean age of 48.6 years) and 71 106 persons in the non-CP cohort were observed for 86 740 and 429 116 person-years, respectively. The CP cohort showed a 2.95-fold greater adjusted hazard ratio (aHR) for DVT (95% confidence interval [CI] 2.06-4.22) and a 4.51-fold greater aHR for PE (95% CI 2.86-7.11) than the non-CP cohort. Substantial risks of DVT and PE were evident in patients with CP aged < 55 years. The CP cohort with comorbidities showed increased risks of DVT and PE as compared with the non-CP cohort with no comorbidities. CONCLUSIONS: The risks of DVT and PE are significantly higher in CP patients than in the general population. PMID- 26563681 TI - Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - Part 3: Mentha * piperita - Solanum dulcamara. AB - This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph - now (since 2015)(?) called a European Union herbal monograph - has been produced. Part 3: Mentha * piperita L.-Solanum dulcamara L. PMID- 26563682 TI - Macronutrient intake regulates sexual conflict in decorated crickets. AB - Sexual conflict results in a diversity of sex-specific adaptations, including chemical additions to ejaculates. Male decorated crickets (Gryllodes sigillatus) produce a gelatinous nuptial gift (the spermatophylax) that varies in size and free amino acid composition, which influences a female's willingness to fully consume this gift. Complete consumption of this gift maximizes sperm transfer through increased retention of the sperm-containing ampulla, but hinders post copulatory mate choice. Here, we examine the effects of protein (P) and carbohydrate (C) intake on the weight and amino acid composition of the spermatophylax that describes its gustatory appeal to the female, as well as the ability of this gift to regulate sexual conflict via ampulla attachment time. Nutrient intake had similar effects on the expression of these traits with each maximized at a high intake of nutrients with a P : C ratio of 1 : 1.3. Under dietary choice, males actively regulated their nutrient intake but this regulation did not coincide with the peak of the nutritional landscape for any trait. Our results therefore demonstrate that a balanced intake of nutrients is central to regulating sexual conflict in G. sigillatus, but males are constrained from reaching the optima needed to bias the outcome of this conflict in their favour. PMID- 26563683 TI - Regarding long-term outcome after kidney donation. PMID- 26563685 TI - Modeling skeletal bone development with hidden Markov models. AB - This paper presents a tool for automatic assessment of skeletal bone age according to a modified version of the Tanner and Whitehouse (TW2) clinical method. The tool is able to provide an accurate bone age assessment in the range 0-6 years by processing epiphysial/metaphysial ROIs with image-processing techniques, and assigning TW2 stage to each ROI by means of hidden Markov models. The system was evaluated on a set of 360 X-rays (180 for males and 180 for females) achieving a high success rate in bone age evaluation (mean error rate of 0.41+/-0.33 years comparable to human error) as well as outperforming other effective methods. The paper also describes the graphical user interface of the tool, which is also released, thus to support and speed up clinicians' practices when dealing with bone age assessment. PMID- 26563684 TI - Effects of unsaturated fatty acids on the kinetics of voltage-gated proton channels heterologously expressed in cultured cells. AB - KEY POINTS: Arachidonic acid (AA) greatly enhances the activity of the voltage gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear. In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells. The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage-dependence of activation. Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms. Application of phospholipase A2 , which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage-gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside-out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current-voltage relationship. In monomeric channels lacking the coiled-coil region of the channel protein, the shift in the current-voltage relationship was diminished but activation and deactivation remained accelerated. Studies with several AA derivatives showed that double bonds and hydrophilic head groups are essential for the effect of AA, although charge was not important. The application of phospholipase A2 (PLA2), which generates AA from cell membrane phospholipids, stimulated mHv1 activity to a similar extent as direct application of ~ 20 MUM AA, suggesting that endogenous AA may regulate Hv channel activity. PMID- 26563686 TI - Exploiting ensemble learning for automatic cataract detection and grading. AB - Cataract is defined as a lenticular opacity presenting usually with poor visual acuity. It is one of the most common causes of visual impairment worldwide. Early diagnosis demands the expertise of trained healthcare professionals, which may present a barrier to early intervention due to underlying costs. To date, studies reported in the literature utilize a single learning model for retinal image classification in grading cataract severity. We present an ensemble learning based approach as a means to improving diagnostic accuracy. Three independent feature sets, i.e., wavelet-, sketch-, and texture-based features, are extracted from each fundus image. For each feature set, two base learning models, i.e., Support Vector Machine and Back Propagation Neural Network, are built. Then, the ensemble methods, majority voting and stacking, are investigated to combine the multiple base learning models for final fundus image classification. Empirical experiments are conducted for cataract detection (two-class task, i.e., cataract or non-cataractous) and cataract grading (four-class task, i.e., non-cataractous, mild, moderate or severe) tasks. The best performance of the ensemble classifier is 93.2% and 84.5% in terms of the correct classification rates for cataract detection and grading tasks, respectively. The results demonstrate that the ensemble classifier outperforms the single learning model significantly, which also illustrates the effectiveness of the proposed approach. PMID- 26563687 TI - Compound identification in forensic toxicological analysis with untargeted LC-MS based techniques. AB - Untargeted LC-MS/MS techniques have become indispensable tools for systematic toxicological analysis. Compound identification is based on the mass spectrometric information obtained, and this may include m/z, isotopic pattern, retention time and fragmentation information. All these different kinds of analytical features can be stored in libraries and databases. Currently, the most competent approach for compound identification involves tandem mass spectral library search. State-of-the-art databases were shown to be sensitive, specific, robust and instrument-independent. Low- and high-resolution instruments can both be used to develop efficient screening workflows. For automated and unattended acquisition of tandem mass spectral data, data-dependent acquisition control is the method of choice. Due to their impressive detection sensitivity, data independent acquisition techniques are finding increased applicability. PMID- 26563688 TI - Utilisation of echocardiography in Australia. PMID- 26563689 TI - Editor's note. PMID- 26563690 TI - Shortfalls in clinical and health system leadership. PMID- 26563691 TI - Antibiotic resistance: are we all doomed? AB - Antibiotic resistance is a growing and worrying problem associated with increased deaths and suffering for people. Overall, there are only two factors that drive antimicrobial resistance, and both can be controlled. These factors are the volumes of antimicrobials used and the spread of resistant micro-organisms and/or the genes encoding for resistance. The One Health concept is important if we want to understand better and control antimicrobial resistance. There are many things we can do to better control antimicrobial resistance. We need to prevent infections. We need to have better surveillance with good data on usage patterns and resistance patterns available across all sectors, both human and agriculture, locally and internationally. We need to act on these results when we see either inappropriate usage or resistance levels rising in bacteria that are of concern for people. We need to ensure that food and water sources do not spread multi resistant micro-organisms or resistance genes. We need better approaches to restrict successfully what and how antibiotics are used in people. We need to restrict the use of 'critically important' antibiotics in food animals and the entry of these drugs into the environment. We need to ensure that 'One Health' concept is not just a buzz word but implemented. We need to look at all sectors and control not only antibiotic use but also the spread and development of antibiotic resistant bacteria - both locally and internationally. PMID- 26563692 TI - B12 deficiency in chronic kidney disease: early recognition matters. PMID- 26563693 TI - Linear erythematous cutaneous adverse reaction during intravenous iloprost administration. PMID- 26563694 TI - Colonoscopy in young women. PMID- 26563695 TI - Author reply: To PMID 25644364. PMID- 26563696 TI - Author reply: To PMID 25109312. PMID- 26563697 TI - When paperwork does not represent the patient's wishes for surrogate decision making. PMID- 26563698 TI - Efficacy of non-invasive ventilation for hypercapnic acute respiratory failure in a general ward: details and comments. PMID- 26563699 TI - Author reply: To PMID 25684643. PMID- 26563700 TI - Facile Synthesis of Novel Networked Ultralong Cobalt Sulfide Nanotubes and Its Application in Supercapacitors. AB - Ultralong cobalt sulfide (CoS(1.097)) nanotube networks are synthesized by a simple one-step solvothermal method without any surfactant or template. A possible formation mechanism for the growth processes is proposed. Owing to the hollow structure and large specific area, the novel CoS(1.097) materials present outstanding electrochemical properties. Electrochemical measurements for supercapacitors show that the as-prepared ultralong CoS(1.097) nanotube networks exhibit high specific capacity, good capacity retention, and excellent Coulombic efficiency. PMID- 26563702 TI - Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams. AB - RATIONALE: Undeclared corticosteroids in creams intended for frequent use might cause serious side-effects, especially in children. In order to prevent this or find the cause, it was essential to develop a method for quick detection and quantification of low levels of corticosteroids. METHODS: Eleven corticosteroids were used in this study: prednisolone, methylprednisolone, prednisolone-21 acetate, fluocinolone acetonide, fluocinolone acetonide-21-acetate, hydrocortisone-21-acetate, dexamethasone, betamethasone, betamethasone dipropionate, clobetasol propionate and triamcinolone. Separation was achieved via liquid chromatography (LC), and mass spectrometric analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry (MS/MS) in the multiple reaction monitoring mode using corticosterone as internal standard. RESULTS: Good separation by using a gradient-elution LC/MS/MS method with run time of 25 min enabled the use of a segmented detection method and consecutive decrease in detection limits. The proposed method has been validated in the linearity range of 10-1000 ng/mL with coefficients of determination higher than 0.990. The method has shown to have very low limits of quantification (0.75-3 ng/mL) with satisfactory precision and accuracy for each of the corticosteroids. CONCLUSIONS: An LC/MS/MS method for the rapid and simultaneous determination of low levels of eleven topical corticosteroids in creams was developed, optimized and validated. The proposed method can be used for testing of different products indicated for the treatment of atopic dermatitis, including "natural products", and "herbal creams" with "miraculous effects". PMID- 26563701 TI - Idiopathic Noncirrhotic Portal Hypertension: An Appraisal. AB - Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID- 26563703 TI - Analysis of stable isotope ratios in blood of tracked wandering albatrosses fails to distinguish a delta(13) C gradient within their winter foraging areas in the southwest Atlantic Ocean. AB - RATIONALE: The main limitation of isotopic tracking for inferring distribution is the lack of detailed reference maps of the isotopic landscape (i.e. isoscapes) in the marine environment. Here, we attempt to map the marine delta(13) C isoscape for the southwestern sector of the Atlantic Ocean, and assess any temporal variation using the wandering albatross as a model species. METHODS: Tracking data and blood and diet samples were collected monthly from wandering albatrosses rearing chicks at Bird Island, South Georgia, during the austral winter between May and October 2009. The delta(13) C and delta(15) N values were measured by mass spectrometry in plasma and blood cells, and related to highly accurate data on individual movements and feeding activity obtained using three types of device: GPS, activity (immersion) loggers and stomach temperature probes. RESULTS: The tracked birds foraged in waters to the north or northwest of South Georgia, including the Patagonian shelf-break, as far as 2000 km from the colony. The foraging region encompassed the two main fronts in the Southern Ocean (Polar and Subantarctic fronts). The delta(13) C values varied by only 2.1 0/00 in plasma and 2.5 0/00 in blood cells, and no relationships were found between the delta(13) C values in plasma and the mean latitude or longitude of landings or feeding events of each individual. CONCLUSIONS: The failure to distinguish a major biogeographic gradient in delta(13) C values suggest that these values in the south Atlantic Ocean are fairly homogeneous. There was no substantial variation among months in either the delta(13) C or the delta(15) N values of plasma or blood cells of tracked birds. As birds did not show a significant change in diet composition or foraging areas during the study period, these results provide no evidence for major temporal variation in stable isotope ratios in consumer tissues, or in the regional marine isoscape in the austral winter of 2009. PMID- 26563704 TI - Analytical method for simultaneous determination of bulk and intramolecular (13) C-isotope compositions of acetic acid. AB - RATIONALE: Headspace solid-phase microextraction (HS-SPME) combined with gas chromatography/pyrolysis-gas chromatography/combustion-isotope ratio mass spectrometry (GC/Py-GC/C-IRMS) was developed for the simultaneous determination of the intramolecular and molecular carbon-isotopic composition (delta(13) C value) of acetic acid. METHODS: The delta(13) C values of carboxyl and methyl carbon were standardized using calibration curves constructed from the regression between the measured delta(13) C values and the delta(13) C values of working standards determined in a previous study. We applied this developed HS-SPME-GC/Py GC/C-IRMS technique to commercial vinegars. RESULTS: In one injection analysis, the bulk and intramolecular delta(13) C values of pure acetic acid standards can be obtained. The repeatability (1sigma) of the bulk delta(13) C values is within +/-0.40/00, and that of the delta(13) Ccarboxyl and delta(13) Cmethyl values is within +/-0.60/00. The intramolecular delta(13) C values of acetic acid in vinegars exhibit a similar pattern. The average Deltadelta value (delta(13) CCOOH - delta(13) CCH3 ) is 4.3 +/- 2.00/00. CONCLUSIONS: The approach presented herein for the molecular and intramolecular delta(13) C determination of acetic acid avoids switching between configuration systems and thereby reduces systematic errors. It is expected to be useful for examining isotope fractionation associated with processes related to organic acid (bio)transformations. PMID- 26563705 TI - Stable chlorine isotope analysis of chlorinated acetic acids using gas chromatography/quadrupole mass spectrometry. AB - RATIONALE: The environmental occurrence of chlorinated acetic acids (CAAs) has been extensively studied, but the sources and transport are still not yet fully understood. A promising approach for source apportionment and process studies is the isotopic characterization of target compounds. We present the first on-line stable chlorine isotope analysis of CAAs by use of gas chromatography/quadrupole mass spectrometry (GC/qMS). METHODS: Following approved procedures for concentration analysis, CAAs extracted into MTBE were methylated to GC-amenable methyl esters (mCAAs). These mCAAs were then analyzed by GC/qMS for their stable chlorine isotope composition using a sample/standard-bracketing approach (CAA standards in the range delta(37) Cl -6.3 to -0.2 0/00, Standard Mean Ocean Chloride). RESULTS: Cross-calibration of the herein presented method with off line reference methods (thermal ionization and continuous-flow GC isotope ratio mass spectrometry; TI-MS and CF-GC/IRMS, respectively) shows good agreement between the methods (regression slope for GC/qMS vs reference method data sets: 0.92 +/- 0.29). Sample amounts as small as 10 pmol Cl can herewith be analyzed with a precision of 0.1 to 0.4 0/00. CONCLUSIONS: This method should be useful for environmental studies of CAAs at ambient concentrations in precipitations (<0.06 to 100 nmol L(-1) ), surface waters (<0.2 to 5 nmol L(-1) ) and soil (<0.6 to 2000 nmol kg(-1) dry soil) where conventional off-line methods cannot be applied. PMID- 26563706 TI - Optimization of a large-volume injection method for compound-specific isotope analysis of polycyclic aromatic compounds at trace concentrations. AB - RATIONALE: Compound-specific isotope analysis (CSIA) of persistent organic contaminants can be used for source apportioning in the environment if appropriate sensitivity can be achieved. This paper describes the optimization and validation of a sensitive analytical approach for the determination of the carbon isotope composition of semi-volatile organic compounds, such as polycyclic aromatic hydrocarbons (PAHs). METHODS: Analyses are based on the introduction of up to 150 MUL of organic extracts by means of programmed temperature vaporization large-volume injection combined with gas chromatography coupled to isotope ratio mass spectrometry (PTV-LVI-GC/IRMS). To allow for the analysis of more volatile, low-molecular-weight PAHs, the PTV injector was equipped with a sub ambient/cryogenic cooling. Accuracy, precision, linearity and determination limits for application in isotope analysis were evaluated for a set of individual PAHs ranging from two- to five-ring molecular structures. The method was exemplified by determining the delta(13) C values of individual PAHs in soil samples in a source apportionment study at a contaminated site. RESULTS: The choice of PTV injection parameters is crucial to prevent isotope fractionation during injection and largely depends on the analytes to be determined. The observed isotope fractionation effect on semi-volatiles depends on the applied solvent and injection temperature and demonstrates the importance of performing appropriate tests with given PTV parameters for each of the compounds of interest. The proposed PTV-LVI-GC/IRMS method allows the carbon isotope ratio (delta(13) C value) of individual PAHs to be determined accurately and precisely at concentrations of 0.04-0.1 ng MUL(-1) even for volatile PAHs such as naphthalene or acenaphthene. CONCLUSIONS: LVI with PTV injector cooling allows for the isotopic analysis of volatile and semi-volatile PAHs at trace concentrations, thus considerably expanding the applicability of CSIA in environmental studies. PMID- 26563707 TI - Development of a suspect and non-target screening approach to detect veterinary antibiotic residues in a complex biological matrix using liquid chromatography/high-resolution mass spectrometry. AB - RATIONALE: Swine manure can contain a wide range of veterinary antibiotics, which could enter the environment via manure spreading on agricultural fields. A suspect and non-target screening method was applied to swine manure samples to attempt to identify veterinary antibiotics and pharmaceutical compounds for a future targeted analysis method. METHODS: A combination of suspect and non-target screening method was developed to identify various veterinary antibiotic families using liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS). The sample preparation was based on the physicochemical parameters of antibiotics for the wide scope extraction of polar compounds prior to LC/HRMS analysis. The amount of data produced was processed by applying restrictive thresholds and filters to significantly reduce the number of compounds found and eliminate matrix components. RESULTS: The suspect and non-target screening was applied on swine manure samples and revealed the presence of seven common veterinary antibiotics and some of their relative metabolites, including tetracyclines, beta-lactams, sulfonamides and lincosamides. However, one steroid and one analgesic were also identified. The occurrence of the identified compounds was validated by comparing their retention times, isotopic abundance patterns and fragmentation patterns with certified standards. CONCLUSIONS: This identification method could be very useful as an initial step to screen for and identify emerging contaminants such as veterinary antibiotics and pharmaceuticals in environmental and biological matrices prior to quantification. PMID- 26563708 TI - Effects of fatty acyl chain length, double-bond number and matrix on phosphatidylcholine responses in matrix-assisted laser desorption/ionization on an Orbitrap mass spectrometer. AB - RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is used for the fast qualitative and quantitative analysis of phosphatidylcholines (PC). Fatty acyl chain lengths and the number of double bonds (DB) affect relative responses of PC; hence the determination of correction factors of individual PC is important for the accurate quantitation. The signal intensity in MALDI-MS strongly depends on the matrix; therefore, the following matrices typically used in lipidomics are studied in the present work: 2,5 dihydroxybenzoic acid (DHB), 1,5-diaminonaphthalene (DAN) and 9-aminoacridine (9AA). METHODS: Series of PC with various fatty acyl chain lengths are synthesized for this study. PC concentrations over two orders of magnitude are studied with MALDI-MS. These experiments provide sets of calibration curves for each of the synthesized PC and the further analysis of parameters of calibration curves is performed. RESULTS: Correction factors for PC decrease with increasing fatty acyl chain length for all matrices. These dependences are steeper for unsaturated PC than for saturated ones. MALDI matrices also have a significant effect on this dependence. The weakest dependence on fatty acyl chain length is found for saturated PC in 9AA. In the case of the other matrices, the effect of fatty acyl chain length on the response is essential for both saturated and unsaturated PC. Calibration curves and parameters of calibration curves for both saturated and monounsaturated PC are fitted by a linear function with regression coefficients decreasing in the order 9AA > DAN > DHB. CONCLUSIONS: Differences in relative responses for PC in MALDI-MS measurements must be taken into account for accurate quantitation. Parameters of calibration curves can be used for the determination of PC concentrations using a single internal standard (IS). This method gives good results for the 9AA matrix, but the reproducibility of measurements for the DHB and DAN matrices is lower and the method can be used for a rough estimation only. These matrices are less convenient for the quantitation of PC. PMID- 26563709 TI - An ultrahigh-resolution mass spectrometry index to estimate natural organic matter lability. AB - RATIONALE: Determining the chemical constituents of natural organic matter (NOM) by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICRMS) remains the ultimate measure for probing its source material, evolution, and transport; however, lability and the fate of organic matter (OM) in the environment remain controversial. FTICRMS-derived elemental compositions are presented in this study to validate a new interpretative method to determine the extent of NOM lability from various environments. METHODS: FTICRMS data collected over the last decade from the same 9.4 tesla instrument using negative electrospray ionization at the National High Magnetic Field Laboratory in Tallahassee, Florida, was used to validate the application of a NOM lability index. Solid-phase extraction cartridges were used to isolate the NOM prior to FTICRMS; mass spectral peaks were calibrated internally by commonly identified NOM homologous series, and molecular formulae were determined for NOM composition and lability analysis. RESULTS: A molecular lability boundary (MLB) was developed from the FTICRMS molecular data, visualized from van Krevelen diagrams, dividing the data into more and less labile constituents. NOM constituents above the MLB at H/C >=1.5 correspond to more labile material, whereas NOM constituents below the MLB, H/C <1.5, exhibit less labile, more recalcitrant character. Of all marine, freshwater, and glacial environments considered for this study, glacial ecosystems were calculated to contain the most labile OM. CONCLUSIONS: The MLB extends our interpretation of FTICRMS NOM molecular data to include a metric of lability, and generally ranked the OM environments from most to least labile as glacial > marine > freshwater. Applying the MLB is useful not only for individual NOM FTICRMS studies, but also provides a lability threshold to compare and contrast molecular data with other FTICRMS instruments that survey NOM from around the world. PMID- 26563710 TI - Comparing ion-pairing reagents and counter anions for ion-pair reversed-phase liquid chromatography/electrospray ionization mass spectrometry analysis of synthetic oligonucleotides. AB - RATIONALE: Ion-pair reversed-phase liquid chromatography/electrospray ionization mass spectrometry (IP-RP-LC/ESI-MS) has been widely used for the quality control of oligonucleotides. However, researchers are still looking to improve mobile phase systems for IP-RP-LC/ESI-MS analysis of oligonucleotides. This study compared the performance of six ion-pairing reagents with three different counter anions for IP-RP-LC/ESI-MS analysis of oligonucleotides. METHODS: The study was performed using a Waters ultra-performance liquid chromatography (UPLC(r)) system coupled to a Waters LCT Premier XE mass spectrometer by using a UPLC(r) OST column (2.1 mm * 100 mm, 1.7 um). Buffer systems containing acetate, bicarbonate, and hexafluoroisopropanolate salts of six ion-pairing reagents (triethylamine, tripropylamine, hexylamine, N,N-dimethylbutylamine, dibutylamine, N,N diisopropylethylamine), respectively, were optimized for IP-RP-LC/ESI-MS analysis of oligonucleotides, and then the optimized conditions were applied for the separation of oligonucleotides. RESULTS: Counter anions definitely play a role in IP-RP-LC/ESI-MS analysis of oligonucleotides. Buffer containing 30 mM diisopropylethylamine and 200 mM hexafluoroisopropanol provided the highest separation of unmodified heterogeneous oligonucleotides, but tripropylammonium hexafluoroisopropanolate achieved the most enhanced separation of sequence isomers. However, triethylammonium acetate and bicarbonate had equally the highest separation for positional isomers. CONCLUSIONS: IP-RP-LC/ESI-MS separation of oligonucleotides is mainly sequence dependent, but it is also dependent on both the type of ion-pairing reagent and counter anion present in the mobile phase. PMID- 26563711 TI - Extensive fragmentation of pheophytin-a by infrared multiphoton dissociation tandem mass spectrometry. AB - RATIONALE: In a previous tandem mass spectrometry (MS/MS) study on chlorophyll-a, infrared multiphoton dissociation (IRMPD) was demonstrated as a more effective fragmentation method than collision-induced dissociation (CID) and electron induced dissociation (EID), where odd-electron product ions were observed ubiquitously in CID and IRMPD. To further understand the role of the macrocycle and the central Mg atom in the MS/MS process, the fragmentation behaviour of pheophytin-a, the Mg-free chlorophyll-a, was investigated. METHODS: CID, IRMPD, and EID were applied to the singly protonated pheophytin-a using an ultra-high resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The result is compared with the MS/MS study of chlorophyll-a. RESULTS: For pheophytin-a, some different fragmentation patterns from chlorophyll-a were obtained by all three MS/MS methods, but IRMPD still appears the most efficient method of generating product ions. The detection of odd-electron fragments in the CID and IRMPD spectra of protonated pheophytin-a suggests that the macrocyclic structure effectively stabilizes radicals, and these radical ions seem to have a relatively higher abundance in the presence of the central Mg atom. CONCLUSIONS: The strong absorption in the infrared region of pheophytin-a and secondary free radical rearrangement are proposed to explain the extensive frgmentation in IRMPD spectra. In addition, a comparison of the IRMPD spectra of chlorophyll-a and pheophytin-a shows that the macrocycle in the absence of the Mg atom is much more fragile. PMID- 26563713 TI - Examination of the Factor Structure of a Global Cognitive Function Battery across Race and Time. AB - Older African Americans tend to perform more poorly on cognitive function tests than older Whites. One possible explanation for their poorer performance is that the tests used to assess cognition may not reflect the same construct in African Americans and Whites. Therefore, we tested measurement invariance, by race and over time, of a structured 18-test cognitive battery used in three epidemiologic cohort studies of diverse older adults. Multi-group confirmatory factor analyses were carried out with full-information maximum likelihood estimation in all models to capture as much information as was present in the observed data. Four different aspects of the data were fit to each model: comparative fit index (CFI), standardized root mean square residuals (SRMR), root mean square error of approximation (RMSEA), and model $$?chi ^{2} $$ . We found that the most constrained model fit the data well (CFI=0.950; SRMR=0.051; RMSEA=0.057 (90% confidence interval: 0.056, 0.059); the model $$?chi ^{2} $$ =4600.68 on 862 df), supporting the characterization of this model of cognitive test scores as invariant over time and racial group. These results support the conclusion that the cognitive test battery used in the three studies is invariant across race and time and can be used to assess cognition among African Americans and Whites in longitudinal studies. Furthermore, the lower performance of African Americans on these tests is not due to bias in the tests themselves but rather likely reflect differences in social and environmental experiences over the life course. (JINS, 2016, 22, 66-75). PMID- 26563714 TI - Comparative results of endoscopic and open methods of vein harvesting for coronary artery bypass grafting: a prospective randomized parallel-group trial. AB - BACKGROUND: We compared wound complications between endoscopic and open great saphenous vein harvesting for coronary artery bypass surgery. METHODS: A total of 228 consecutive patients were prospectively randomized into two groups: open vein harvesting (OVH), 115 patients; and endoscopic vein harvesting (EVH), 113 patients. Each group was assessed for post-operative wound complications, pain intensity, and neuropathy in the early post-surgical period. Lymphoscintigraphy of the lower limbs as well as morphological studies of vein walls using light and electron scanning microscopy were performed. RESULTS: Vein harvesting time was shorter for EVH than OVH: 31.8 +/- 6.2 min and 40.3 +/- 15.8 min, respectively (p < 0.01). There were fewer complications after vein harvesting in the EVH group (11.5 %) than in the OVH group (44.4 %) (r = 0.001). Multivariate analysis showed that diabetes mellitus was the only risk factor for post-surgical complications after OVH (odds ratio = 3.95 %; 95 % confidence interval 1.03-8.6). Lymphoscintigraphic data in the EVH group did not demonstrate considerable disturbances in lymph drainage after surgery. In the OVH group, the accumulation of radiopharmaceutical drugs in the lymphatic nodes reduced two-fold (r <= 0.001). Histological evaluation of vein samples did not show considerable damage to the vein wall in either group. CONCLUSIONS: Using electron microscopy of vein fragments, this study demonstrated that EVH reduces wound complications and provides good-quality conduits. PMID- 26563715 TI - Management of gastric cancer: East vs West. PMID- 26563716 TI - Seasonal dynamics of the fish assemblage in a floodplain lake at the confluence of the Negro and Amazon Rivers. AB - The temporal effect of discharge and limnology on fish composition and species diversity in a floodplain lake at the confluence of the Amazon and Negro Rivers was evaluated. Species richness, abundance and assemblage composition were strongly influenced by seasonal discharge of the Amazon and Negro Rivers, which affects lateral connectivity, water conductivity and temperature. As a consequence, temporal beta-diversity was high in the lake and the assemblage was dominated by seasonally transient species. Relatively large species known to feed on resources within the floodplain were captured almost exclusively during the flood period. During the dry season, the assemblage was dominated by fishes adapted to harsh conditions of high temperature and low dissolved oxygen concentrations. An open system with high spatial and temporal heterogeneity created by the meeting of two large rivers with different water chemistry, Lago Catalao has a dynamic fish assemblage. Given its high temporal beta-diversity and abundance of fishes, many of great importance in local fisheries, Lago Catalao and other floodplain lakes in this region merit special attention for conservation. PMID- 26563717 TI - Hasday: Treatment of obesity in 10th century. PMID- 26563718 TI - The occurrence of musculoskeletal complaints among professional musicians: a systematic review. AB - PURPOSE: This study gives a systematic overview of the literature on the occurrence of musculoskeletal complaints in professional instrumental musicians. METHODS: A systematic review. Nine literature databases were searched without time limits on June 25, 2015, also the complete index of the journal Medical Problems of Performing Artists (MPPA) until June 2015 (30;2) was searched, and citation tracking and reference checking of the selected articles were performed. The search consisted of the combination of three groups of keywords: musician (e.g., musician, violin, music student, instrument player) AND musculoskeletal (e.g., musculoskeletal, tendon, shoulder, arthritis) AND epidemiology (e.g., prevalence, incidence, occurrence). RESULTS: The initial literature search strategy resulted in 1258 potentially relevant articles. Finally, 21 articles describing 5424 musicians were included in this review. Point prevalences of musculoskeletal complaints in professional musicians range between 9 and 68 %; 12 month prevalences range between 41 and 93 %; and lifetime prevalences range between 62 and 93 %. Ten out of 12 studies show a higher prevalence of musculoskeletal complaints among women. Brass instrumentalists are reported to have the lowest prevalence rates of musculoskeletal complaints. The neck and shoulders are the anatomic areas most affected; the elbows are least affected. Although some information is reported concerning age, the high risk of bias in and between these studies makes it impossible to present reliable statements with respect to this. CONCLUSION: Musculoskeletal symptoms are highly prevalent among musicians, especially among women instrumentalists. Future research concerning the epidemiology of musculoskeletal complaints among musicians should focus on associated risk factors and follow the current guidelines to optimize scientific quality. PMID- 26563719 TI - Sensory modulation of movement, posture and locomotion. AB - During voluntary movement, there exists a well known functional sensory attenuation of afferent inputs, which allows us to discriminate between information related to our own movements and those arising from the external environment. This attenuation or 'gating' prevents some signals from interfering with movement elaboration and production. However, there are situations in which certain task-relevant sensory inputs may not be gated. This review begins by identifying the prevalent findings in the literature with specific regard to the somatosensory modality, and reviews the many cases of classical sensory gating phenomenon accompanying voluntary movement and their neural basis. This review also focuses on the newer axes of research that demonstrate that task-specific sensory information may be disinhibited or even facilitated during engagement in voluntary actions. Finally, a particular emphasis will be placed on postural and/or locomotor tasks involving strong somatosensory demands, especially for the setting of the anticipatory postural adjustments observed prior the initiation of locomotion. PMID- 26563720 TI - The discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C. AB - INTRODUCTION: Hepatitis C virus (HCV) infection is a worldwide health problem, whose management has been revolutionized after the availability of sofosbuvir, a direct-acting antiviral (DAAs). Sofosbuvir is a HCV NS5B polymerase inhibitor. Antiviral regimens including sofosbuvir are associated with success rates >90%, even in the case of "difficult-to-treat" patients such as subjects with liver cirrhosis as well as prior null response to IFN and ribavirin. AREAS COVERED: This drug discovery case history focuses on the pre-clinical and clinical development of sofosbuvir. The authors analyze all of the main steps leading to the global approval of sofosbuvir. The paper also highlights the encouraging data from the subsequent trials wherein sofosbuvir was tested in combination with other DAAs (IFN- and often ribavirin-free regimens) and from first real life studies. EXPERT OPINION: Sofosbuvir is a very powerful weapon in the new armamentarium against HCV. Thanks to its valuable features including its pangenotypic activity, once-daily oral administration, its excellent tolerability, and safety profile, it represents the backbone of several effective regimens, in combination with IFN or with other DAAs (IFN-free therapies). Regimens including sofosbuvir have quickly become the touchstone for all the novel anti-HCV treatments. PMID- 26563721 TI - Foreword: Association Between Prenatal Exposure to Maternal Infection and Offspring Mood Disorders: A Review of the Literature. PMID- 26563722 TI - Deep and surface learning in problem-based learning: a review of the literature. AB - In problem-based learning (PBL), implemented worldwide, students learn by discussing professionally relevant problems enhancing application and integration of knowledge, which is assumed to encourage students towards a deep learning approach in which students are intrinsically interested and try to understand what is being studied. This review investigates: (1) the effects of PBL on students' deep and surface approaches to learning, (2) whether and why these effects do differ across (a) the context of the learning environment (single vs. curriculum wide implementation), and (b) study quality. Studies were searched dealing with PBL and students' approaches to learning. Twenty-one studies were included. The results indicate that PBL does enhance deep learning with a small positive average effect size of .11 and a positive effect in eleven of the 21 studies. Four studies show a decrease in deep learning and six studies show no effect. PBL does not seem to have an effect on surface learning as indicated by a very small average effect size (.08) and eleven studies showing no increase in the surface approach. Six studies demonstrate a decrease and four an increase in surface learning. It is concluded that PBL does seem to enhance deep learning and has little effect on surface learning, although more longitudinal research using high quality measurement instruments is needed to support this conclusion with stronger evidence. Differences cannot be explained by the study quality but a curriculum wide implementation of PBL has a more positive impact on the deep approach (effect size .18) compared to an implementation within a single course (effect size of -.05). PBL is assumed to enhance active learning and students' intrinsic motivation, which enhances deep learning. A high perceived workload and assessment that is perceived as not rewarding deep learning are assumed to enhance surface learning. PMID- 26563723 TI - [Infantile pyknocytosis: A cause of noenatal hemolytic anemia. Is recombinant erythropoietin an alternative to transfusion?]. AB - Infantile pyknocytosis is a neonatal hemolytic disorder which causes anemia and icterus and is characterized by the presence of an increased number of distorted red blood cells called pyknocytes. Resolution spontaneously occurs in the first semester of life. It has been generally described as a rare entity, with an occasional family history. We report seven cases of infantile pyknocytosis observed in our hospital in 3 years. Most of the infants presented with hemolytic icterus and profound anemia that was reaching its peak by the 3rd week of life. Three neonates received one to three red blood cell transfusions, according to former recommendations. However, the following four received a treatment with recombinant erythropoietin administered subcutaneously. Only one of these four cases required a transfusion. All of them were free of hematological disease 2-3 months after completion of treatment. Infantile pyknocytosis is a recognized cause of neonatal hemolytic anemia, which requires careful examination of red cell morphology on a peripheral blood smear. The cause of this transient disorder remains unknown. Our observations show that recombinant erythropoietin therapy is effective in treating infantile pyknocytosis and increases the reticulocyte response, thus improving the hemoglobin level. PMID- 26563724 TI - [Peroneal nerve palsy in children: Uncommon diagnosis of a proximal tibiofibular synovial cyst]. AB - Compression of the common peroneal nerve by synovial cysts of the tibiofibular joint is a rare disease. Two macroscopic forms may be encountered: extraneural cysts and intraneural cysts. In a review of the literature, we found only three pediatric cases of common peroneal nerve palsy due to extraneural cysts and about 60 cases reported in adults. Taking advantage of the clinical history of two children operated in our department for this disease, we describe this uncommon entity, which must be diagnosed and treated rapidly. Even in the presence of severe clinical and electrophysiological symptoms, a full clinical recovery is possible, as observed in these two children. However, follow-up is needed because recurrence is possible. PMID- 26563725 TI - [Acute renal failure after dengue virus infection: A pediatric case report]. AB - Dengue is an emerging, rapidly expanding disease, whose clinical and biological manifestations vary. Kidney injury is not usual but can be severe, and it is most often associated with dengue hemorrhagic fever or shock. Guadeloupe, which is located in an endemic area, experienced an epidemic from 2013 to 2014. During this outbreak, a case of renal failure during dengue was observed in a 10-year old child. No evidence of dengue hemorrhagic fever or shock syndrome was found. The clinical and biological course improved with symptomatic treatment. The association of acute renal failure with hemolytic anemia suggested a diagnosis of hemolytic uremic syndrome. However, this could not be confirmed in the absence of thrombocytopenia and cytopathologic evidence. This case illustrates the diversity of clinical presentations of dengue, and the possibility of severe renal impairment unrelated to the usual factors encountered in dengue. PMID- 26563726 TI - [Vaccine news]. PMID- 26563727 TI - Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole. AB - Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06+/-0.15, 8.17+/-0.47, 11.04+/-0.73, 11.49+/-0.92, 12.52+/-1.04 and 16.9+/ 1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40+/-0.02MUg/mL) compared with orally administered free ABZ (0.19+/ 0.07MUg/mL) as well as conventional tablet (0.20+/-0.05MUg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. PMID- 26563728 TI - (11)C- and (18)F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography. AB - P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4 ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2 fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4 tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5 methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET. PMID- 26563729 TI - Primary Tumor Resection Is Associated with Improved Survival in Stage IV Colorectal Cancer: An Instrumental Variable Analysis. AB - Primary tumor resection (PTR) is recommended for patients with unresectable stage IV colorectal cancer (CRC) who present with symptoms related to their primary tumor. However, the survival benefit of PTR for asymptomatic patients is controversial. We investigated the change in PTR rates and the contribution of PTR to survival in patients with unresectable stage IV CRC over the past two decades in the United States. Clinicopathological factors and long-term survival were compared for 44 514 patients diagnosed with unresectable stage IV CRC from January 1, 1988, through December 31, 2010, who had or had not undergone PTR. Multivariable Cox regression and the instrumental variable method were used to identify independent factors for survival. Of the 44 514 patients with unresectable stage IV CRC, 27 931 (62.7%) had undergone PTR. The annual rate of PTR decreased from 74.4% to 50.2% diagnosed in 1988 and 2010, and the median overall survival increased for both PTR and non-PTR patients. Instrumental variable analyses revealed that PTR was associated with better overall, cancer specific, and other-cause survival of patients with unresectable stage IV CRC. PMID- 26563730 TI - Pre-clinical evaluation of therapies to prevent or treat bone non-union: a systematic review protocol. AB - BACKGROUND: Non-union of fractured bone is a major cause of morbidity in the orthopaedic population. Despite this, optimal management of non-union is still unclear and remains a significant clinical challenge. Research continues in animal models in an attempt to identify an effective clinical treatment. The proposed systematic review will evaluate current therapies of bone non-union in animal models, in order to identify those that may translate successfully to clinical therapies. METHODS/DESIGN: The methodology for the systematic review will be in accordance with standard guidelines. All potential sources for pre clinical studies will be interrogated and the search strategy written in conjunction with a specialist in this field. Data extraction will be conducted by two reviewers to minimise bias. Analysis will be predominantly qualitative because of the heterogeneity that is likely to exist between the studies. However, quantitative synthesis will be performed where homogeneity in a sub group of studies exists. Quality assessment will be undertaken utilising a risk of bias tool. DISCUSSION: To date, there has not been a systematic review addressing bone non-union therapies in animal models despite the plethora of pre clinical research currently being undertaken. This protocol details and outlines the methodology and justification for such a review. PMID- 26563731 TI - Cyclopent-2-enylaluminium as allylzinc precursor for the diastereoselective allylmetallation of non-racemic imines: applications to the synthesis of enantiomerically enriched heterocycles. AB - The generation of cyclopent-2-enylzinc from cyclopentadiene based on a titanium catalyzed hydroalumination/transmetallation sequence is described. Applied to the allylmetallation of phenylglycinol-derived imines, this sequence leads to homoallylic amines with moderate to good stereoselectivities. The synthesis of disubstituted azetidines and piperidines illustrates the potential of the method. PMID- 26563732 TI - Evaluation of executive functions in children and adolescents with familial Mediterranean fever. AB - The aim of the present study was to investigate neuropsychological test performance in children and adolescents with familial Mediterranean fever (FMF). A total of 88 children and adolescents aged 8 to 17 years were included, 52 with FMF and 36 healthy controls. After the participants were administered the Children Depression Inventory (CDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED), they completed the battery tests of the Central Nervous System Vital Signs (CNSVS), a neurocognitive test battery, via computer. The battery calculates seven domain scores (Memory, Psychomotor Speed, Processing Speed, Reaction Time, Complex Attention, Executive Function, and Cognitive Flexibility) and a summary score (Neurocognition Index [NCI]). A statistically significant difference between the FMF and control groups was found in six out of seven domains, where the scores of the participants with FMF were found to be significantly lower than those of the control participants (p < .05). Although the mean Reaction Time score of the participants with FMF was found to be lower than that of the control participants, the finding was not statistically significant (p > .05). The mean CDI and SCARED scores of the participants with FMF were found to be significantly higher than those of the control participants (p < .05). Low scores in the Processing Speed and Psychomotor Speed domains of the CNSVS were significantly correlated with higher SCARED scores (r = -.37, p = .01). Impaired cognitive functions should be taken into consideration in children and adolescents with FMF when assessing and managing this population. PMID- 26563733 TI - Suppression of autophagy by extracellular vesicles promotes myofibroblast differentiation in COPD pathogenesis. AB - Extracellular vesicles (EVs), such as exosomes and microvesicles, encapsulate proteins and microRNAs (miRNAs) as new modulators of both intercellular crosstalk and disease pathogenesis. The composition of EVs is modified by various triggers to maintain physiological homeostasis. In response to cigarette smoke exposure, the lungs develop emphysema, myofibroblast accumulation and airway remodelling, which contribute to chronic obstructive pulmonary disease (COPD). However, the lung disease pathogenesis through modified EVs in stress physiology is not understood. Here, we investigated an EV-mediated intercellular communication mechanism between primary human bronchial epithelial cells (HBECs) and lung fibroblasts (LFs) and discovered that cigarette smoke extract (CSE)-induced HBEC derived EVs promote myofibroblast differentiation in LFs. Thorough evaluations of the modified EVs and COPD lung samples showed that cigarette smoke induced relative upregulation of cellular and EV miR-210 expression of bronchial epithelial cells. Using co-culture assays, we showed that HBEC-derived EV miR-210 promotes myofibroblast differentiation in LFs. Surprisingly, we found that miR 210 directly regulates autophagy processes via targeting ATG7, and expression levels of miR-210 are inversely correlated with ATG7 expression in LFs. Importantly, autophagy induction was significantly decreased in LFs from COPD patients, and silencing ATG7 in LFs led to myofibroblast differentiation. These findings demonstrate that CSE triggers the modification of EV components and identify bronchial epithelial cell-derived miR-210 as a paracrine autophagy mediator of myofibroblast differentiation that has potential as a therapeutic target for COPD. Our findings show that stressor exposure changes EV compositions as emerging factors, potentially controlling pathological disorders such as airway remodelling in COPD. PMID- 26563734 TI - Diversity of extracellular vesicles in human ejaculates revealed by cryo-electron microscopy. AB - Human ejaculates contain extracellular vesicles (EVs), that to a large extent are considered to originate from the prostate gland, and are often denominated "prostasomes." These EVs are important for human fertility, for example by promoting sperm motility and by inducing immune tolerance of the female immune system to the spermatozoa. So far, the EVs present in human ejaculate have not been studied in their native state, inside the seminal fluid without prior purification and isolation procedures. Using cryo-electron microscopy and tomography, we performed a comprehensive inventory of human ejaculate EVs. The sample was neither centrifuged, fixed, filtered or sectioned, nor were heavy metals added. Approximately 1,500 extracellular structures were imaged and categorized. The extracellular environment of human ejaculate was found to be diverse, with 5 major subcategories of EVs and 6 subcategories of extracellular membrane compartments, including lamellar bodies. Furthermore, 3 morphological features, including electron density, double membrane bilayers and coated surface, are described in all subcategories. This study reveals that the extracellular environment in human ejaculate is multifaceted. Several novel morphological EV subcategories are identified and clues to their cellular origin may be found in their morphology. This inventory is therefore important for developing future experimental approaches, and to interpret previously published data to understand the role of EVs for human male fertility. PMID- 26563735 TI - Handling and storage of human body fluids for analysis of extracellular vesicles. AB - Because procedures of handling and storage of body fluids affect numbers and composition of extracellular vesicles (EVs), standardization is important to ensure reliable and comparable measurements of EVs in a clinical environment. We aimed to develop standard protocols for handling and storage of human body fluids for EV analysis. Conditions such as centrifugation, single freeze-thaw cycle, effect of time delay between blood collection and plasma preparation and storage were investigated. Plasma is the most commonly studied body fluid in EV research. We mainly focused on EVs originating from platelets and erythrocytes and investigated the behaviour of these 2 types of EVs independently as well as in plasma samples of healthy subjects. EVs in urine and saliva were also studied for comparison. All samples were analysed simultaneously before and after freeze thawing by resistive pulse sensing, nanoparticle tracking analysis, conventional flow cytometry (FCM) and transmission (scanning) electron microscopy. Our main finding is that the effect of centrifugation markedly depends on the cellular origin of EVs. Whereas erythrocyte EVs remain present as single EVs after centrifugation, platelet EVs form aggregates, which affect their measured concentration in plasma. Single erythrocyte and platelet EVs are present mainly in the range of 100-200 nm, far below the lower limit of what can be measured by conventional FCM. Furthermore, the effects of single freeze-thaw cycle, time delay between blood collection and plasma preparation up to 1 hour and storage up to 1 year are insignificant (p>0.05) on the measured concentration and diameter of EVs from erythrocyte and platelet concentrates and EVs in plasma, urine and saliva. In conclusion, in standard protocols for EV studies, centrifugation to isolate EVs from collected body fluids should be avoided. Freezing and storage of collected body fluids, albeit their insignificant effects, should be performed identically for comparative EV studies and to create reliable biorepositories. PMID- 26563736 TI - Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress. AB - This review outlines recent advancements in the understanding of athlete immune health. Controversies discussed include whether high levels of athletic training and environmental stress (for example, heat acclimation, cryotherapy and hypoxic training) compromise immunity and increase upper respiratory tract infection (URTI). Recent findings challenge early exercise immunology doctrine by showing that international athletes performing high-volume training suffer fewer, not greater, URTI episodes than lower-level performers and URTI incidence decreases, not increases, around the time of competition compared with heavy training. Herein we raise the possibility of host genetic influences on URTI and modifiable behavioural and training-related factors underpinning these recent observations. Continued controversy concerns the proportion of URTI symptoms reported by athletes that are due to infectious pathogens, airway inflammation or as yet unknown causes and indeed whether the proportion differs in athletes and non athletes. Irrespective of the cause of URTI symptoms (infectious or non infectious), experts broadly agree that self-reported URTI hinders high-volume athletic training but, somewhat surprisingly, less is known about the influence on athletic performance. In athletes under heavy training, both innate and acquired immunity are often observed to decrease, typically 15-25%, but whether relatively modest changes in immunity increase URTI susceptibility remains a major gap in knowledge. With the exception of cell-mediated immunity that tends to be decreased, exercising in environmental extremes does not provide an additional threat to immunity and host defence. Recent evidence suggests that immune health may actually be enhanced by regular intermittent exposures to environmental stress (for example, intermittent hypoxia training). PMID- 26563737 TI - Vascular comorbidities and demographics of patients with ruptured abdominal aortic aneurysms. AB - BACKGROUND: The results of previous studies reporting the epidemiology of ruptured abdominal aortic aneurysm (RAAA) are highly heterogeneous. Furthermore, although RAAA and the preceding abnormal dilation of the abdominal aorta (AAA) are associated with other cardiovascular comorbidities, the demographic profile of all patients with RAAA has not been thoroughly investigated. OBJECTIVE: To document accurately the epidemiology, survival, and demographic data (including vascular comorbidities and previous use of health care services) in RAAA patients. MATERIAL AND METHODS: We conducted a comprehensive retrospective register study of all RAAA patients (operatively treated RAAA patients as well as in- and out-of-hospital nonsurvivors) in a well-defined geographic area during an 11-year period. RESULTS: We found 488 RAAA cases in a catchment area of 689,000. The annual incidence of RAAA was 6.5/100,000. Of these patients 43.2% were underwent surgery. Overall mortality was 79.5%, and 27.5% of the population died out-of-hospital. Age was the only independent risk factor affecting survival (P < .0001). The mean age at the time of RAAA was 73.6 years for men and 82.3 years for women. Off all unexpected RAAA patients, 40% had a previous history of cardiovascular disease (most often coronary artery disease: 32%), and 38% had visited a physician within the previous year. CONCLUSION: RAAA remains a highly lethal condition with age as the only significant risk factor for mortality. The proportion of women increases strongly with age. A large proportion of patients with unexpected RAAA have history of cardiovascular disease. PMID- 26563738 TI - Expanding the role of rosuvastatin as a pulmonary-protective agent. PMID- 26563739 TI - Using interstimulus interval to maximise sensitivity of the Psychomotor Vigilance Test to fatigue. AB - There is some evidence that short interstimulus intervals (ISIs) on the Psychomotor Vigilance Test (PVT) are associated with longer and more varied reaction times (RTs). Preparation processes may impede RT following short ISIs, resulting in additional unexplained variance. The aims of this study were to investigate whether there is an effect of ISI on RT and errors within the PVT, and whether such an effect changes with three elements of fatigue: time of day, prior wake and time on task. Twelve male participants completed 49 PVTs across 7* 28h periods of forced desynchrony. For analysis, RTs, reciprocal reaction times (1/RT), false starts and lapse responses within each 10min session were assigned to a 1-s ISI group, a 2-min time of task group, a 2.5-h PW level and a 60 degrees phase of the circadian rhythm of core body temperature (as a measure of time of day). Responses following short ISIs (2-5s) were significantly slower and more varied than responses following longer ISIs (5-10s). The likelihood of a lapse was also higher for short ISIs, while the probability of a false start increased as a function of ISI. These effects were independent of the influences of time of day, prior wake and time on task. Hence, mixed model ANOVAs comprising only long ISIs (5-10s) contained stronger effect sizes for fatigue than a model of all ISIs (2-10s). Including an ISI variable in a model improved the model fit and explained more variance associated with fatigue. Short ISIs resulted in long RTs both in the presence and absence of fatigue, possibly due to preparation processes or ISI conditioning. Hence, omitting short ISI trials from RT means or including an ISI variable in analysis can reduce unwanted variance in PVT data, improving the sensitivity of the PVT to fatigue. PMID- 26563740 TI - Vibrational Properties of h-BN and h-BN-Graphene Heterostructures Probed by Inelastic Electron Tunneling Spectroscopy. AB - Inelastic electron tunneling spectroscopy is a powerful technique for investigating lattice dynamics of nanoscale systems including graphene and small molecules, but establishing a stable tunnel junction is considered as a major hurdle in expanding the scope of tunneling experiments. Hexagonal boron nitride is a pivotal component in two-dimensional Van der Waals heterostructures as a high-quality insulating material due to its large energy gap and chemical mechanical stability. Here we present planar graphene/h-BN-heterostructure tunneling devices utilizing thin h-BN as a tunneling insulator. With much improved h-BN-tunneling-junction stability, we are able to probe all possible phonon modes of h-BN and graphite/graphene at Gamma and K high symmetry points by inelastic tunneling spectroscopy. Additionally, we observe that low-frequency out of-plane vibrations of h-BN and graphene lattices are significantly modified at heterostructure interfaces. Equipped with an external back gate, we can also detect high-order coupling phenomena between phonons and plasmons, demonstrating that h-BN-based tunneling device is a wonderful playground for investigating electron-phonon couplings in low-dimensional systems. PMID- 26563742 TI - Allergic contact dermatitis in children: trends in allergens, 10 years on. A retrospective study of 500 children tested between 2005 and 2014 in one UK centre. AB - BACKGROUND: Contact allergy in children is becoming increasingly recognized as a cause of eczema. The causal agents may change with time, but there are few comparative data for this age group. OBJECTIVES: To compare data from the past 10 years with a similar study from the previous decade. METHODS: Between 2005 and 2014, 500 consecutive children who had been patch tested at Leeds Teaching Hospitals were identified, and the results were reviewed. RESULTS: Twenty-seven per cent (134 cases) of children had one or more positive patch test findings. The mean +/- standard deviation age of patients with a positive test reaction was 11.9 +/- 4.1 years, which was significantly higher than that of patients with a negative result (10.9 +/- 4.0 years) (p = 0.01; Mann-Whitney U-test). No significant relationship between sex and a positive patch test result was found (p = 0.48, chi-squared). Allergy to nickel was the most frequent finding, although this accounted for 18%, rather than 33% (1995-2004), of all positive reactions. The next most common allergens included fragrance mix 1 (17%), p phenylenediamine (16%), and methylchloroisothiazolinone/methylisothiazolinone (6%). CONCLUSIONS: Although the overall incidence of contact allergy in our paediatric population is static, there has been a significant change in the allergens detected, probably as a result of changes in European legislation and cosmetic product use in children. PMID- 26563743 TI - Prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy: a systematic review and external validation study. AB - ESSENTIALS: Prediction models may help to identify patients at high risk of bleeding on antiplatelet therapy. We identified existing prediction models for bleeding and validated them in patients with cerebral ischemia. Five prediction models were identified, all of which had some methodological shortcomings. Performance in patients with cerebral ischemia was poor. SUMMARY: Background Antiplatelet therapy is widely used in secondary prevention after a transient ischemic attack (TIA) or ischemic stroke. Bleeding is the main adverse effect of antiplatelet therapy and is potentially life threatening. Identification of patients at increased risk of bleeding may help target antiplatelet therapy. OBJECTIVE: This study sought to identify existing prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy and evaluate their performance in patients with cerebral ischemia. METHODS: We systematically searched PubMed and Embase for existing prediction models up to December 2014. The methodological quality of the included studies was assessed with the CHARMS checklist. Prediction models were externally validated in the European Stroke Prevention Study 2, comprising 6602 patients with a TIA or ischemic stroke. We assessed discrimination and calibration of included prediction models. RESULTS: Five prediction models were identified, of which two were developed in patients with previous cerebral ischemia. Three studies assessed major bleeding, one studied intracerebral hemorrhage and one gastrointestinal bleeding. None of the studies met all criteria of good quality. External validation showed poor discriminative performance, with c-statistics ranging from 0.53 to 0.64 and poor calibration. CONCLUSION: A limited number of prediction models is available that predict intracranial hemorrhage or major bleeding in patients on antiplatelet therapy. The methodological quality of the models varied, but was generally low. Predictive performance in patients with cerebral ischemia was poor. In order to reliably predict the risk of bleeding in patients with cerebral ischemia, development of a prediction model according to current methodological standards is needed. PMID- 26563741 TI - Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury. AB - Overproduction of hydrogen peroxide (H2O2) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H2O2-activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H2O2 and release HBA (p hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H2O2-stimulated cells by suppressing the generation of ROS and pro inflammatory cytokines. In mouse models of hepatic I/R and cardiac I/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H2O2-scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H2O2-activatable antioxidant prodrug for the treatment of I/R injuries. PMID- 26563744 TI - Dutch Young Adults Ratings of Behavior Change Techniques Applied in Mobile Phone Apps to Promote Physical Activity: A Cross-Sectional Survey. AB - BACKGROUND: Interventions delivered through new device technology, including mobile phone apps, appear to be an effective method to reach young adults. Previous research indicates that self-efficacy and social support for physical activity and self-regulation behavior change techniques (BCT), such as goal setting, feedback, and self-monitoring, are important for promoting physical activity; however, little is known about evaluations by the target population of BCTs applied to physical activity apps and whether these preferences are associated with individual personality characteristics. OBJECTIVE: This study aimed to explore young adults' opinions regarding BCTs (including self-regulation techniques) applied in mobile phone physical activity apps, and to examine associations between personality characteristics and ratings of BCTs applied in physical activity apps. METHODS: We conducted a cross-sectional online survey among healthy 18 to 30-year-old adults (N=179). Data on participants' gender, age, height, weight, current education level, living situation, mobile phone use, personality traits, exercise self-efficacy, exercise self-identity, total physical activity level, and whether participants met Dutch physical activity guidelines were collected. Items for rating BCTs applied in physical activity apps were selected from a hierarchical taxonomy for BCTs, and were clustered into three BCT categories according to factor analysis: "goal setting and goal reviewing," "feedback and self-monitoring," and "social support and social comparison." RESULTS: Most participants were female (n=146), highly educated (n=169), physically active, and had high levels of self-efficacy. In general, we observed high ratings of BCTs aimed to increase "goal setting and goal reviewing" and "feedback and self-monitoring," but not for BCTs addressing "social support and social comparison." Only 3 (out of 16 tested) significant associations between personality characteristics and BCTs were observed: "agreeableness" was related to more positive ratings of BCTs addressing "goal setting and goal reviewing" (OR 1.61, 95% CI 1.06-2.41), "neuroticism" was related to BCTs addressing "feedback and self-monitoring" (OR 0.76, 95% CI 0.58-1.00), and "exercise self-efficacy" was related to a high rating of BCTs addressing "feedback and self-monitoring" (OR 1.06, 95% CI 1.02-1.11). No associations were observed between personality characteristics (ie, personality, exercise self efficacy, exercise self-identity) and participants' ratings of BCTs addressing "social support and social comparison." CONCLUSIONS: Young Dutch physically active adults rate self-regulation techniques as most positive and techniques addressing social support as less positive among mobile phone apps that aim to promote physical activity. Such ratings of BCTs differ according to personality traits and exercise self-efficacy. Future research should focus on which behavior change techniques in app-based interventions are most effective to increase physical activity. PMID- 26563745 TI - Iron-Carbonyl Aqueous Vesicles (MCsomes) by Hydration of [Fe(CO){CO(CH2)5CH3}(Cp)(PPh3)] (FpC6): Highly Integrated Colloids with Aggregation-Induced Self-Enhanced IR Absorption (AI-SEIRA). AB - Self-assembly of hydrophobic molecules into aqueous colloids contradicts common chemical intuition, but has been achieved through hydration of [Fe(CO){CO(CH2)5CH3}(Cp)(PPh3)] (FpC6). FpC6 has no surface activity, no NMR signals in D2O and no critical aggregation concentration (CAC) in H2O. The molecule, however, contains both acyl and terminal CO groups that are prone to being hydrated. By adding water to a solution in THF, self-assembly of FpC6 can be initiated through water-carbonyl interactions (WCIs) with the highly polarized acyl CO groups. This aggregation subsequently enhances the hydration of the acyl CO groups and also induces the WCI of otherwise unhydrated terminal CO groups. The resultant metal-carbonyl aggregates have been proved to be bilayer vesicles with iron complexes exposed towards water and alkyl chains forming inner walls (MCsomes). These MCsomes show high structure integration upon dilution due to the hydrophobic nature of the building blocks. The highly polarized CO groups on the surface of the MCsomes result in a negative zeta potential (-65 mV) and create a local electric field, which significantly enhances the IR absorption of CO groups by more than 100-fold. This is the first discovery of aggregation-induced self enhanced IR absorption (AI-SRIRA) without the assistant of external dielectric substrates. Highly integrated MCsomes are, therefore, promising as a novel group of materials, for example, for IR-based sensing and imaging. PMID- 26563746 TI - Letter to the Editor: Regarding HPV vaccination in patients who are infected with an oncogenic subtype. PMID- 26563747 TI - Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons. AB - The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 MUm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ~60% and ~48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN 93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. PMID- 26563748 TI - Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells. AB - Surfactant protein D (SP-D) is an integral molecule of the innate immunity secreted by epithelial cells lining the mucosal surfaces. The C-type lectin domain of SP-D performs pattern recognition functions while it binds to putative receptors on immune cells to modify cellular functions. Activation of immune cells and increased serum SP-D is observed in a range of patho-physiological conditions including infections. We speculated if SP-D can modulate systemic immune response via direct interaction with activated PBMCs. In this study, we examined interaction of a recombinant fragment of human SP-D (rhSP-D) on PHA activated PBMCs. We report a significant downregulation of activation receptors such as TLR2, TLR4, CD11c and CD69 upon rhSP-D treatment. rhSP-D inhibited production of Th1 (TNF-alpha and IFN-gamma) and Th17 (IL-17A) cytokines along with IL-6. Interestingly, levels of IL-2, Th2 (IL-4) and regulatory (IL-10 and TGF-beta) cytokines remained unaltered. Analysis of co-stimulatory CD28 and co inhibitory CTLA4 receptors along with their ligands CD80 and CD86 revealed a selective up-regulation of CTLA4 in the lymphocyte subset. rhSP-D induced apoptosis in the activated but not in non-activated lymphocytes. Blockade of CTLA4 inhibited rhSP-D mediated apoptosis of activated lymphocytes, confirming involvement of CTLA4. We conclude that SP-D restores immune homeostasis. It regulates expression of immunomodulatory receptors and cytokines, which is followed by induction of apoptosis in activated lymphocytes. These findings suggest a critical role of SP-D in immune surveillance against activated immune cells. PMID- 26563750 TI - Heterogeneity of the Mac-1 expression on peripheral blood neutrophils in patients with different types of epithelial ovarian cancer. AB - The expression level of Mac-1 on the surface of neutrophils is an important indicator of neutrophil activation. Under pathological conditions, Mac-1 is believed a key adhesion molecule that facilitates cancer progression and mediates the adhesion of tumour cells to the endothelium of blood vessels. Our previous findings indicated that circulating peripheral blood neutrophils in patients with advanced epithelial ovarian cancer (EOC) expressed enhanced levels of Mac-1, which was functionally associated with an increased adhesive function of neutrophils. The objective of the current study was to analyse whether the value of individual components of the differential white cell count, including the neutrophil and lymphocyte ratios, which are markers of blood neutrophil activation, might be associated with certain types of ovarian cancer. We showed the increase in Mac-1 expression along with a parallel decrease of L-selectin and PSGL-1 on peripheral blood neutrophils of patients with EOC of early and advanced FIGO stages, which indicates an activated state of neutrophils in comparison to neutrophils of individuals without cancer. Despite a significant difference between Mac-1 expression in patients with and without cancer, a dramatic increase in Mac-1 expression was observed in the blood of patients with undifferentiated carcinomas compared with patients with other histological types of EOC. Moreover, the expression level of Mac-1 correlated with the number of neutrophils in patients with serous, endometrioid and undifferentiated EOC. The results of an ROC analysis demonstrated that the patients with the undifferentiated type of EOC form a distinct group with regard to Mac-1 expression on blood neutrophils. The results suggested a diverse biological cadre of immune cells in patients with undifferentiated ovarian carcinomas compared with patients with other histological types of EOC. PMID- 26563749 TI - ISG15 expression correlates with HIV-1 viral load and with factors regulating T cell response. AB - Given the multifactorial nature of action of type I interferon (IFN) in HIV-1 infection and the need to firmly establish the action of key components of IFN pathways, we compared the IFN stimulated gene (ISG)15 expression with that of other well-characterized ISGs, evaluating its relationship with immunosuppressive factors regulating T-cell response in HIV-1 patients. PBMC from 225 subjects were included: healthy donors (n=30), naive (n=93) and HAART treated HIV-1 subjects (n=102). Levels of ISG15-mRNA, ISG56-mRNA, APOBEC3G/3F-mRNA, TRAIL-mRNA, IDO mRNA, proviral load andISG15 (rs15842 and rs1921) SNPs were evaluated by using TaqMan assays. We found that ISG15, ISG56, APOBEC3G/3F levels were increased in untreated HIV-1 patients compared to healthy donors, being ISG15 the highest ISG expressed. The amount of ISG15 correlated with viral load and with CD4+ T cell counts whereas no relationship was found between all ISGs analyzed and proviral load or HIV-1 tropism. ISG15 expression was reduced following long-term antiretroviral therapy. In addition, ISG15 levels were correlated with those of TRAIL and IDO in HIV-1 viremic patients. Lastly, ISG15 SNPs had no influence on ISG15 levels. We demonstrates that ISG15 is elevated in viremic HIV-1 patients and is associated with high TRAIL and IDO levels. PMID- 26563751 TI - 16th Annual Land O'Lakes Bioanalytical Conference. AB - This Land O'Lakes Conference is presented each year by the Division of Pharmacy Professional Development within the School of Pharmacy at the University of Wisconsin-Madison (USA). The purpose of this 3-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference, the program is a mixture of lectures, interactive discussions and a poster session. This report summarized the presentations at the 16th Annual Conference. 6th Annual Land O'Lakes Bioanalytical Conference, Fluno Center Madison, WI, USA, 13-16 July 2015. PMID- 26563752 TI - Abiotic mediation of a mutualism drives herbivore abundance. AB - Species abundance is typically determined by the abiotic environment, but the extent to which such effects occur through the mediation of biotic interactions, including mutualisms, is unknown. We explored how light environment (open meadow vs. shaded understory) mediates the abundance and ant tending of the aphid Aphis helianthi feeding on the herb Ligusticum porteri. Yearly surveys consistently found aphids to be more than 17-fold more abundant on open meadow plants than on shaded understory plants. Manipulations demonstrated that this abundance pattern was not due to the direct effects of light environment on aphid performance, or indirectly through host plant quality or the effects of predators. Instead, open meadows had higher ant abundance and per capita rates of aphid tending and, accordingly, ants increased aphid population growth in meadow but not understory environments. The abiotic environment thus drives the abundance of this herbivore exclusively through the mediation of a protection mutualism. PMID- 26563753 TI - Discrimination of Umami Tastants Using Floating Electrode-Based Bioelectronic Tongue Mimicking Insect Taste Systems. AB - We report a floating electrode-based bioelectronic tongue mimicking insect taste systems for the detection and discrimination of umami substances. Here, carbon nanotube field-effect transistors with floating electrodes were hybridized with nanovesicles containing honeybee umami taste receptor, gustatory receptor 10 of Apis mellifera (AmGr10). This strategy enables us to discriminate between l monosodium glutamate (MSG), best-known umami tastant, and non-umami substances with a high sensitivity and selectivity. It could also be utilized for the detection of MSG in liquid food such as chicken stock. Moreover, we demonstrated the synergism between MSG and disodium 5'-inosinate (IMP) for the umami taste using this platform. This floating electrode-based bioelectronic tongue mimicking insect taste systems can be a powerful platform for various applications such as food screening, and it also can provide valuable insights on insect taste systems. PMID- 26563754 TI - Advancing Geriatrics Education Through a Faculty Development Program for Geriatrics-Oriented Clinician Educators. AB - Geriatrician and nongeriatrician faculty need instruction as teachers to provide quality training for a broader community of physicians who can care for the expanding population of older adults. Educators at Duke University designed a program to equip geriatrician and nongeriatrician faculty to develop quality educational programs and teach medical learners about geriatrics. Eighty-three faculty representing 52 institutions from across the United States participated in mini-fellowship programs (2005-09) consisting of workshops and 1-year follow up mentoring by Duke faculty. Participants attended 1-week on-campus sessions on curriculum development and teaching skills and designed and implemented a curriculum in their home institution. Participant specialties included general medicine (nearly 50%), family medicine, surgery, psychiatry, rehabilitation medicine, and emergency medicine. Pre- and postprogram self-efficacy surveys, program evaluation surveys, and 6- and 12-month progress reports on scholars' educational projects were used to assess the effect of the Duke mini-fellowship programs on participants' educational practices. Forty-four scholars (56%) completed the end-of-year self-efficacy survey and end-of-program evaluation. Self-efficacy results indicated significant gains (P < .001) in 12 items assessed at 1 week and 1 year. Scholars reported the largest average gains at 1 year in applying adult learning principles in the design of educational programs (1.72), writing measurable learning objectives (1.51), and identifying optimal instructional methods to deliver learning objectives (1.50). Participants described improved knowledge and skills in designing curricula, implemented new and revised geriatrics curricula, and demonstrated commitment to faculty development and improving learning experiences for medical learners. This faculty development program improved participants' self-efficacy in curriculum design and teaching and enhanced geriatrics education in their home institutions. PMID- 26563755 TI - Rs12976445 Polymorphism is Associated with Risk of Diabetic Nephropathy Through Modulating Expression of MicroRNA-125 and Interleukin-6R. AB - BACKGROUND: Diabetic nephropathy (DN) is one of the most significant long-term complications of diabetes mellitus (DM), and it is a primary risk factor for end stage renal disease. MicroRNAs (miRNAs) play important roles in regulating the expression of genes, including interleukin-6R (IL-6R), which has been reported to be involved in the development of DNDN. The aim of this study was to identify the dysregulation of miRNA and its target responsible for the development of DN in DM. MATERIAL AND METHODS: We collected the kidney tissues from patients with DN (N=36) and control patients (N=28), and performed real-time PCR and Western blot analysis to determine the expression of IL-6R. Computational analysis and luciferase assay were used to identify the miRNA that regulates IL-6R. To explore the association between rs12976445 polymorphism and risk of DN, we enrolled 594 DM patients with (N=282) or without DN (N=312), and studied the association between a variant in miR-125a and risk of DN in DM. RESULTS: The expression of IL 6R was barely detected in the control groups, while in the DN group, the IL-6R was clearly detectable. Next, miR-125a was identified as a regulator of IL-6R by using informatics analysis and luciferase assay. A single-nucleotide polymorphism (rs12976445) in pri-miR-125a has been shown to compromise the mature processing of miR-125a, and we showed that the expression levels of miR-125a was comparable between individuals carrying TT and CT, and when combined into 1 group, the miR 125a expression was approximately 3 times lower than in the CC group. We found significant differences regarding rs12976445 genotype distribution between the DN and the control (OR=1.45, 95% C.I.=1.02-2.08, p<0.05) with the possible confounding factors adjusted for by using logistic regression analysis. CONCLUSIONS: We identified miR-125a as a direct regulator of IL-6R, and the genotype of rs12976445 might be a novel predictor of the development of DN in DM. PMID- 26563756 TI - Chronic Methamphetamine Self-Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat. AB - The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant methamphetamine (METH). Recent findings have implicated the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in oxytocin modulation of acute METH reward and relapse to METH-seeking behaviour. Surprisingly, the oxytocin receptor (OTR) is only modestly involved in both regions in oxytocin attenuation of METH primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant-induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NAc core and STh, as well as changes to oxytocin plasma levels, after chronic METH i.v. self-administration (IVSA) and after extinction of drug-taking. An additional aim was to examine whether changes to central corticotrophin-releasing factor (CRF) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress-regulatory mechanisms. Male Sprague-Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed-ratio 1 schedule or received yoked saline infusions during 2-h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA. Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NAc core and STh coronal sections. Rats that self-administered METH had higher oxytocin plasma levels, and decreased OTR immunoreactive (-IR) fibres in the NAc core than yoked controls. In animals that self-administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR-IR fibre density increased in the STh, and a trend towards normalisation of OTR-IR fibre density was evident in the NAc core. CRF-IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally within the NAc core and STh, as well as peripherally through plasma measures, are dysregulated after METH abuse. PMID- 26563757 TI - Baby-Led Introduction to SolidS (BLISS) study: a randomised controlled trial of a baby-led approach to complementary feeding. AB - BACKGROUND: In 2002, the World Health Organization recommended that the age for starting complementary feeding should be changed from 4 to 6 months of age to 6 months. Although this change in age has generated substantial debate, surprisingly little attention has been paid to whether advice on how to introduce complementary foods should also be changed. It has been proposed that by 6 months of age most infants will have developed sufficient motor skills to be able to feed themselves rather than needing to be spoon-fed by an adult. This has the potential to predispose infants to better growth by fostering better energy self regulation, however no randomised controlled trials have been conducted to determine the benefits and risks of such a "baby-led" approach to complementary feeding. This is of particular interest given the widespread use of "Baby-Led Weaning" by parents internationally. METHODS/DESIGN: The Baby-Led Introduction to SolidS (BLISS) study aims to assess the efficacy and acceptability of a modified version of Baby-Led Weaning that has been altered to address potential concerns with iron status, choking and growth faltering. The BLISS study will recruit 200 families from Dunedin, New Zealand, who book into the region's only maternity hospital. Parents will be randomised into an intervention (BLISS) or control group for a 12-month intervention with further follow-up at 24 months of age. Both groups will receive the standard Well Child care provided to all parents in New Zealand. The intervention group will receive additional parent contacts (n = 8) for support and education on BLISS from before birth to 12 months of age. Outcomes of interest include body mass index at 12 months of age (primary outcome), energy self-regulation, iron and zinc intake and status, diet quality, choking, growth faltering and acceptability to parents. DISCUSSION: This study is expected to provide insight into the feasibility of a baby-led approach to complementary feeding and the extent to which this method of feeding affects infant body weight, diet quality and iron and zinc status. Results of this study will provide important information for health care professionals, parents and health policy makers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001133820 . PMID- 26563758 TI - Identification of plasma microRNA profiles for primary resistance to EGFR-TKIs in advanced non-small cell lung cancer (NSCLC) patients with EGFR activating mutation. AB - BACKGROUND: EGFR mutation is a strong predictor of efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) therapy in advanced non small cell lung cancer (NSCLC). However, around 20-30 % of EGFR-mutated cases showed no response to EGFR-TKIs, suggesting that other determinants beyond EGFR mutation likely exist. This study analyzed the role of microRNAs (miRNAs) in primary resistance to EGFR-TKIs in advanced NSCLC patients with EGFR mutation. METHODS: Training group: 20 advanced NSCLC patients with EGFR 19 deletion treated with first-line EGFR-TKIs were enrolled; half of them had dramatic responses while the other half had primary resistance. Matched plasma samples were collected for miRNA profiling using TaqMan low-density array (TLDA). Bioinformatics analyses were used to identify related miRNAs possibly accounted for resistance. Testing group: Quantitative reverse transcriptase PCR (qRT-PCR) was employed to detect the level of miRNA with significant differential expression in the training set. Validation group: Another cohort with EGFR 19 deletion mutations, who had dramatically different responses to EGFR-TKI, was used to validate the difference of miRNA expression between the sensitive and resistant groups using RT-PCR. RESULTS: Training group: 153 miRNAs were found to be differentially expressed between the sensitive and resistant groups. Potential target genes were predicted with a target scan database. Twelve differentially expressed miRNAs were selected for the analysis because of their known roles in tumorigenesis of lung cancer, resistance to drugs, and regulation of EGFR pathway. Training group: three out of the 12 miRNAs (miR-21, AmiR-27a, and miR 218) were verified to have significantly higher expression (P miR-21 = 0.004, P miR-27a = 0.009, P miR-218 = 0.041, respectively) in the resistant group compared to the sensitive group. Validation group: The expression levels of these three miRNAs were validated to be significantly different (P = 0.011, 0.011, 0.026, respectively) in the validation cohort (n = 34). CONCLUSIONS: Higher expression levels of miR-21, AmiR-27a, and miR-218 detected in this study suggest potential roles of these miRNAs in primary resistance to EGFR-TKI in advanced NSCLC patients with EGFR exon 19 deletion mutations. These findings need to be further confirmed in a study with a larger sample size. PMID- 26563759 TI - Visualization of Vibrational Modes in Real Space by Tip-Enhanced Non-Resonant Raman Spectroscopy. AB - We present a general theory to model the spatially resolved non-resonant Raman images of molecules. It is predicted that the vibrational motions of different Raman modes can be fully visualized in real space by tip-enhanced non-resonant Raman scattering. As an example, the non-resonant Raman images of water clusters were simulated by combining the new theory and first-principles calculations. Each individual normal mode gives rise its own distinct Raman image, which resembles the expected vibrational motions of the atoms very well. The characteristics of intermolecular vibrations in supermolecules could also be identified. The effects of the spatial distribution of the plasmon as well as nonlinear scattering processes were also addressed. Our study not only suggests a feasible approach to spatially visualize vibrational modes, but also provides new insights in the field of nonlinear plasmonic spectroscopy. PMID- 26563760 TI - Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge. AB - Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds. PMID- 26563761 TI - HIV, Hepatitis C, and Other Sexually Transmitted Infections Among Male Sex Workers in Ho Chi Minh City, Vietnam. AB - There is little data on the burden of HIV and other infections that affect male sex workers (MSW) in Vietnam. We conducted behavioral and biological sexual health surveys with 300 MSW in Ho Chi Minh City. Generalized estimating equation models were built to assess factors associated with HIV, hepatitis C, and other sexually transmitted infections (STI). Of 300 MSW, 19 (6.3 %) were diagnosed seropositive for HIV, 11 (3.7 %) had hepatitis C, and 26 (8.7 %) had at least one prevalent STI. In a multivariable model, opiate use was significantly associated with HIV infection (aOR 6.46, 95 % CI 1.28-32.7) and hepatitis C (aOR = 19.6, 95 % CI 2.35-163.6). Alcohol dependency was associated with increased odds of hepatitis C (aOR = 4.79, 95 % CI 1.02-22.5) and decreased odds of other STI (aOR = 0.30, 95 % CI 0.10-0.97). These findings suggest that MSW in Vietnam would benefit from regular HIV and STI testing, as well as linkage to care and substance use rehabilitation services. PMID- 26563762 TI - Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Neonates. AB - BACKGROUND: Acute kidney injury (AKI) is common in preterm infants and is associated with high mortality and morbidity. New biomarkers for the early detection of AKI have been identified. Specifically, urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a new and powerful biomarker for AKI and sepsis. Our study evaluated the reference range of uNGAL in healthy neonates in Taiwan. METHODS: This study examined 24 preterm and 38 term infants without clinical complications. Urine samples were collected and the uNGAL values were measured at postnatal age (PNA) 3 days, 7 days, 14 days, and 21 days in the preterm infants and at PNA 3 days in the term infants. The uNGAL values were tested using enzyme-linked immunosorbent assay. RESULTS: The median uNGAL values in the preterm infants at PNA 3 days, 7 days, 14 days, and 21 days were 41.52 ng/mL, 35.82 ng/mL, 43.79 ng/mL, and 30.85 ng/mL, respectively. The median value at PNA 3 days in the term infants was 88.1 ng/mL. No significant differences associated with gestational age, birth body weight, or PNA were observed among the preterm infants. However, the uNGAL values in the female term infants were higher than those in the male term infants (p = 0.003). CONCLUSION: This study presents preliminary data on uNGAL levels in neonates in Taiwan. A large-scale study investigating the correlations between uNGAL and with gestational age, birth body weight, sex, and PNA is recommended. PMID- 26563763 TI - Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis. AB - BACKGROUND: Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness. METHODS: We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate. DISCUSSION: While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013005608. ( http://www.crd.york.ac.uk/PROSPERO/ ). PMID- 26563765 TI - The Role of Individual Differences and Situational Variables in the Use of Workplace Sexual Identity Management Strategies. AB - Examination of individual difference variables have been largely ignored within research on the use of workplace sexual identity management strategies. The current study examined personality traits (extraversion, openness, and neuroticism), facets of sexual identity development (identity confusion, internalized heterosexism), and situational variables (e.g., perceptions of workplace climate and heterosexism) in explaining the use of management strategies, as well as possible interactions between individual and situational factors. Perceptions of the workplace climate toward lesbian and gay individuals significantly related to the use each of the management strategies, and Internalized Heterosexism was found to significantly predict the use of the Explicitly Out strategy. Most interactions between individual difference and situational variables were not supported, with the exception of an interaction between workplace heterosexism and internalized homophobia in explaining the use of the Explicitly Out strategy. PMID- 26563764 TI - Determinants of ligand binding and catalytic activity in the myelin enzyme 2',3' cyclic nucleotide 3'-phosphodiesterase. AB - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme highly abundant in the central nervous system myelin of terrestrial vertebrates. The catalytic domain of CNPase belongs to the 2H phosphoesterase superfamily and catalyzes the hydrolysis of nucleoside 2',3'-cyclic monophosphates to nucleoside 2'-monophosphates. The detailed reaction mechanism and the essential catalytic amino acids involved have been described earlier, but the roles of many amino acids in the vicinity of the active site have remained unknown. Here, several CNPase catalytic domain mutants were studied using enzyme kinetics assays, thermal stability experiments, and X-ray crystallography. Additionally, the crystal structure of a perdeuterated CNPase catalytic domain was refined at atomic resolution to obtain a detailed view of the active site and the catalytic mechanism. The results specify determinants of ligand binding and novel essential residues required for CNPase catalysis. For example, the aromatic side chains of Phe235 and Tyr168 are crucial for substrate binding, and Arg307 may affect active site electrostatics and regulate loop dynamics. The beta5-alpha7 loop, unique for CNPase in the 2H phosphoesterase family, appears to have various functions in the CNPase reaction mechanism, from coordinating the nucleophilic water molecule to providing a binding pocket for the product and being involved in product release. PMID- 26563766 TI - Patients with carotid atherosclerosis who underwent or did not undergo carotid endarterectomy: outcome on mood, cognition and quality of life. AB - BACKGROUND: To compare the six-month outcome on mood, cognition and quality of life (QoL) in patients with severe carotid atherosclerosis (CA) who underwent carotid endarterectomy (CEA) with subjects who refused treatment. METHODS: Cohort study on consecutive inpatients with CA (stenosis >= 50 %) (N = 46; age 72.56 +/- 7.26; male 65.2 %). Intervention cohort: subjects who decided to undergo CEA (N = 35); Control cohort patients who refused CEA (N = 11). DSM-IV-Psychiatric diagnosis made by clinicians using interviews, QoL measured by Short Form Health Survey (SF-12); cognitive performance by WAIS Intelligent Coefficient (IC). RESULTS: The study showed a better improvement during six months in Overall IC, Performance IC and Verbal IC in the group that underwent CEA. QoL in the two cohorts did not reach statistical significance. Percentages of patients who improved in the CEA group were significantly higher with regard to Overall and Verbal IC scores, and at the limits of statistical significance in Performance IC. The differences of subject with improvement in SF-12 score in the two groups did not reach statistical significance. Ages below 68 were found to be determinant of a good outcome in Overall IC score. Limit: study conducted with a small sample size. CONCLUSIONS: Patients with severe carotid atherosclerosis who underwent CEA enhanced their cognitive performance. PMID- 26563767 TI - Acute coronary syndromes with significant troponin increase in patients with hip fracture prior to surgical repair: differential diagnosis and clinical implications. AB - Myocardial infarction after hip fracture but before surgical repair is associated with a 30-day mortality as high as 30 % at 1 month. In Florence, since 2011, hip fractures are referred to a multidisciplinary hip fracture team including internal medicine specialists, anesthesiologists, and orthopaedic surgeons. The aim of the present investigation was to evaluate the clinical characteristics of patients with hip fracture who had at hospital admission a significant increase of troponin (>10 times reference levels), the diagnostic and therapeutic strategies adopted, and overall 1-year survival. Protocol at admission included careful clinical evaluation (including bedside echocardiography) in order to stratify surgical risk and schedule surgery and anaesthesiology strategy. 21/1025 patients had preoperative significant troponin increase. In sixteen patients, a diagnosis of NSTEMI was made, five presented with ST elevation. In five patients with NSTEMI considered at very high surgical risk (ASA >= 3, severe cognitive and functional impairment), surgery was not performed. None survived at 1 year. Hip surgery was performed in the other 11. Four underwent coronary revascularization after hip surgery. In this group, 1-year survival was 80 %. Four of five ST elevation patients fulfilled criteria for stress cardiomyopathy confirmed by angiography. Hip surgery was performed, and the patients are alive at 1-year follow-up. Close to 2 % of patients with hip fracture are found to have a significant troponin increase before surgery. Three out of four have an NSTEMI diagnosis. In patients undergoing hip surgery, survival at 1 year is close to 80 %. In patients with ST elevation at admission, stress cardiomyopathy should be considered in the differential diagnosis. This clinical condition is associated with a favourable prognosis after hip surgery. PMID- 26563768 TI - Does inferior vena cava respiratory variability predict fluid responsiveness in spontaneously breathing patients? AB - INTRODUCTION: We have almost no information concerning the value of inferior vena cava (IVC) respiratory variations in spontaneously breathing ICU patients (SBP) to predict fluid responsiveness. METHODS: SBP with clinical fluid need were included prospectively in the study. Echocardiography and Doppler ultrasound were used to record the aortic velocity-time integral (VTI), stroke volume (SV), cardiac output (CO) and IVC collapsibility index (cIVC) ((maximum diameter (IVCmax)- minimum diameter (IVCmin))/ IVCmax) at baseline, after a passive leg raising maneuver (PLR) and after 500 ml of saline infusion. RESULTS: Fifty-nine patients (30 males and 29 females; 57 +/- 18 years-old) were included in the study. Of these, 29 (49 %) were considered to be responders (>=10 % increase in CO after fluid infusion). There were no significant differences between responders and nonresponders at baseline, except for a higher aortic VTI in nonresponders (16 cm vs. 19 cm, p = 0.03). Responders had a lower baseline IVCmin than nonresponders (11 +/- 5 mm vs. 14 +/- 5 mm, p = 0.04) and more marked IVC variations (cIVC: 35 +/- 16 vs. 27 +/- 10 %, p = 0.04). Prediction of fluid responsiveness using cIVC and IVCmax was low (area under the curve for cIVC at baseline 0.62 +/- 0.07; 95 %, CI 0.49-0.74 and for IVCmax at baseline 0.62 +/- 0.07; 95 % CI 0.49-0.75). In contrast, IVC respiratory variations >42 % in SBP demonstrated a high specificity (97 %) and a positive predictive value (90 %) to predict an increase in CO after fluid infusion. CONCLUSIONS: In SBP with suspected hypovolemia, vena cava size and respiratory variability do not predict fluid responsiveness. In contrast, a cIVC >42 % may predict an increase in CO after fluid infusion. PMID- 26563769 TI - The Relationship Between Provider Competence, Content Exposure, and Consumer Outcomes in Illness Management and Recovery Programs. AB - Provider competence may affect the impact of a practice. The current study examined this relationship in sixty-three providers engaging in Illness Management and Recovery with 236 consumers. Improving upon previous research, the present study utilized a psychometrically validated competence measure in the ratings of multiple Illness Management and Recovery sessions from community providers, and mapped outcomes onto the theory underlying the practice. Provider competence was positively associated with illness self-management and adaptive coping. Results also indicated baseline self-management skills and working alliance may affect the relationship between competence and outcomes. PMID- 26563770 TI - Is vitamin D supplementation a viable treatment for Crohn's disease? AB - Vitamin D, important for maintaining bone health in Crohn's disease (CD), may have potential as a treatment for the core inflammatory disease process. There is plausible evidence in favor of vitamin D as an anti-inflammatory from animal models, epidemiological and cross sectional studies of CD. Few clinical trials, however, have been published and therefore the translation of this promise into clinical benefit for people with CD remains unclear. The purpose of this piece is to consider the viability of vitamin D as a treatment for CD based on the current available evidence. PMID- 26563771 TI - Household food security and infant feeding practices in rural Bangladesh. AB - OBJECTIVE: To determine the association between household food security and infant complementary feeding practices in rural Bangladesh. DESIGN: Prospective, cohort study using structured home interviews during pregnancy and 3 and 9 months after delivery. We used two indicators of household food security at 3-months' follow-up: maternal Food Composition Score (FCS), calculated via the World Food Programme method, and an HHFS index created from an eleven-item food security questionnaire. Infant feeding practices were characterized using WHO definitions. SETTING: Two rural sub-districts of Kishoreganj, Bangladesh. SUBJECTS: Mother child dyads (n 2073) who completed the 9-months' follow-up. RESULTS: Complementary feeding was initiated at age <=4 months for 7 %, at 5-6 months for 49 % and at >=7 months for 44 % of infants. Based on 24 h dietary recall, 98 % of infants were still breast-feeding at age 9 months, and 16 % received >=4 food groups and >=4 meals (minimally acceptable diet) in addition to breast milk. Mothers' diet was more diverse than infants'. The odds of receiving a minimally acceptable diet for infants living in most food-secure households were three times those for infants living in least food-secure households (adjusted OR=3.0; 95 % CI 2.1, 4.3). Socio-economic status, maternal age, literacy, parity and infant sex were not associated with infant diet. CONCLUSIONS: HHFS and maternal FCS were significant predictors of subsequent infant feeding practices. Nevertheless, even the more food-secure households had poor infant diet. Interventions aimed at improving infant nutritional status need to focus on both complementary food provision and education. PMID- 26563772 TI - High-resolution NMR-based metabolic detection of microgram biopsies using a 1 mm HRMUMAS probe. AB - A prototype 1 mm High-Resolution micro-Magic Angle Spinning (HRMUMAS) probe is described. High quality (1)H NMR spectra were obtained from 490 MUg of heterogeneous biospecimens, offering a rich-metabolite profiling. The results demonstrate the potential of HRMUMAS as a new NMR analytical tool in metabolomics. PMID- 26563773 TI - Mask-like Metastases: Skin Metastases With a Very Poor Prognosis. PMID- 26563774 TI - Malignant Spiradenoma: a Giant Cutaneous Adnexal Tumor. PMID- 26563775 TI - Optimization of an automated IS addition system for use in high-throughput quantitative DBS analysis. AB - BACKGROUND: Automated DBS direct elution systems are available that incorporate IS spray modules which, unlike conventional IS addition via the extraction solvent, apply IS prior to DBS samples prior to extraction, allowing analyte and IS to be coextracted. RESULTS: IS spray system parameters were optimized to identify the conditions that produced the best analytical performance in quantitative bioanalytical assays, without interfering with the integrity of the DBS sample prior to extraction. CONCLUSION: LC-MS/MS method validations across four representative small molecule assays using the optimized IS spray conditions were demonstrated to produce analytical performance comparable to conventional methods of IS addition, demonstrating that the spray technique is a viable alternative. PMID- 26563776 TI - Assessing the feasibility of a mobile health-supported clinical decision support system for nutritional triage in oncology outpatients using Arden Syntax. AB - BACKGROUND: Nutritional screening procedures followed by regular nutrition monitoring for oncological outpatients are no standard practice in many European hospital wards and outpatient settings. As a result, early signs of malnutrition are missed and nutritional treatment is initiated when patients have already experienced severe weight loss. OBJECTIVE: We report on a novel clinical decision support system (CDSS) for the global assessment and nutritional triage of the nutritional condition of oncology outpatients. The system combines clinical and laboratory data collected in the clinical setting with patient-generated data from a smartphone application for monitoring the patients' nutritional status. Our objective is to assess the feasibility of a CDSS that combines the aforementioned data sources and describe its integration into a hospital information system. Furthermore, we collected patients' opinions on the value of the system, and whether they would regard the system as a useful aid in coping with their condition. MATERIALS AND METHODS: The system implements the Patient Generated Subjective Global Assessment (PG-SGA) to monitor nutritional status in the outpatient setting. A smartphone application is used to collect patient generated data by performing weekly mini-surveys on patients concerning their eating habits, weight, and overall well-being. Data are uploaded on completion of each mini-survey and stored on a secure server at the Medical University of Vienna (MUV). The data are then combined with relevant clinical information from the Vienna General Hospital (VGH) information system. The knowledge base for the CDSS is implemented in medical logic modules (MLMs) using Arden Syntax. A three month pilot clinical trial was performed to test the feasibility of the system. Qualitative questionnaires were used to obtain the patients' opinions on the usability and personal value of the system during the four-week test period. RESULTS: We used the existing separation between the scientific and clinical data domains in the secured network environment (SNE) at the MUV and VGH to our advantage by importing, storing, and processing both patient-generated and routine data in the scientific data domain. To limit exposure to the SNE, patient generated data stored outside the SNE were imported to the scientific domain once a day. The CDSS created for nutritional assessment and triage comprised ten MLMs, each including either a sub-assessment or the final results of the PG-SGA. Finally, an interface created for the hospital information system showed the results directly in clinical routine. In all 22 patients completed the clinical study. The results of the questionnaires showed that 91% of the patients were generally happy with the usability of the system, 91% believed that the application was of additional value in detecting cancer-related malnutrition, and 82% found it helpful as a long-term monitoring tool. DISCUSSION AND CONCLUSION: Despite strict protection of the clinical data domain, a CDSS employing patient generated data can be integrated into clinical routine. The CDSS discussed in this report combined the information entered into a smartphone application with clinical data in order to inform the physician of a patient's nutritional status and thus permit suitable and timely intervention. The initial results show that the smartphone application was well accepted by patients, who considered it useful, but not many oncological outpatients were willing to participate in the clinical study because they did not possess an Android phone or lacked smartphone expertise. Furthermore, the results indicate that patient-generated data could be employed to augment clinical data and calculate metrics such as the PG-SGA without excessive effort by using a secure intermediate location as the locus of data storage and processing. PMID- 26563777 TI - Phylogenetic structural equation modelling reveals no need for an 'origin' of the leaf economics spectrum. AB - The leaf economics spectrum (LES) is a prominent ecophysiological paradigm that describes global variation in leaf physiology across plant ecological strategies using a handful of key traits. Nearly a decade ago, Shipley et al. (2006) used structural equation modelling to explore the causal functional relationships among LES traits that give rise to their strong global covariation. They concluded that an unmeasured trait drives LES covariation, sparking efforts to identify the latent physiological trait underlying the 'origin' of the LES. Here, we use newly developed phylogenetic structural equation modelling approaches to reassess these conclusions using both global LES data as well as data collected across scales in the genus Helianthus. For global LES data, accounting for phylogenetic non-independence indicates that no additional unmeasured traits are required to explain LES covariation. Across datasets in Helianthus, trait relationships are highly variable, indicating that global-scale models may poorly describe LES covariation at non-global scales. PMID- 26563779 TI - Principles and practice of occupational neurology: an overview. AB - Diseases of both central and peripheral nervous systems may be the consequence of chemical and physical exposures occurring in the workplace. The resulting syndromes depend upon the type of hazard, of exposure (acute vs chronic), and of neuronal organization that is affected. Diagnosis of occupational neurologic diseases may prove to be difficult because they rarely display pathognomonic signs and almost always a quantitative assessment of exposure is missing. Therefore medical and occupational histories are of paramount importance and often represent the only source of information to establish causality. Prevention of occupational neurologic disorders requires industrial hygiene programs, ergonomic interventions, and the monitoring of workers. Neuroepidemiology may detect unrecognized and subtle subclinical effects of exposure, including behavioral disorders, and it may also represent the appropriate tool to investigate outbreaks of neurologic diseases in a community. However, in some circumstances the results of neuroepidemiologic studies are controversial because of defects in study design. PMID- 26563778 TI - AKAP6 inhibition impairs myoblast differentiation and muscle regeneration: Positive loop between AKAP6 and myogenin. AB - Skeletal muscle regeneration occurs continuously to repair muscle damage incurred during normal activity and in chronic disease or injury. Herein, we report that A kinase anchoring protein 6 (AKAP6) is important for skeletal myoblast differentiation and muscle regeneration. Compared with unstimulated skeletal myoblasts that underwent proliferation, differentiated cells show significant stimulation of AKAP6 expression. AKAP6 knockdown with siRNA effectively halts the formation of myotubes and decreases the expression of the differentiation markers myogenin and myosin heavy chain. When shAKAP6-lentivirus is delivered to mice with cardiotoxin (CTX)-induced muscle injury, muscle regeneration is impaired compared with that of mice injected with control shMock-lentivirus. The motor functions of mice infected with shAKAP6-lentivirus (CTX+shAK6) are significantly worse than those of mice infected with shMock-lentivirus (CTX+shMock). Mechanistic analysis showed that AKAP6 promotes myogenin expression through myocyte enhancer factor 2A (MEF2A). Notably, myogenin increases AKAP6 expression as well. The results of chromatin immunoprecipitation and luciferase assays showed that myogenin binds to an E-box site on the AKAP6 promoter. Taken together, our findings demonstrate a novel interplay between AKAP6 and myogenin, and we suggest that AKAP6 is an important regulator of myoblast differentiation, myotube formation, and muscle regeneration. PMID- 26563780 TI - Evaluating suspected work-related neurologic disorders (clinical diagnosis). AB - The clinical diagnosis of work-related neurologic disorders is essentially one of exclusion because symptoms and signs are often nonspecific. The clinical reasoning requires a three-step approach: (1) establish the characteristics of the presenting disease; (2) ascertain that observed clinical features are consistent with those caused by the suspected agent(s); and (3) assess occupational exposures. A detailed history is of paramount importance in evaluating patients with suspected work-related neurologic disorders as it is in other clinical contexts, especially because in some circumstances it may represent the only criterion to establish causality. Thus, besides characterization of neurologic symptoms, including their location, quality, timecourse, and possible other associated symptoms, the work environment of the patient should be understood in full detail. In this respect, when a neurotoxin is suspected, then the history collection can be guided by the knowledge of the likely syndromes it produces. Similarly, physical examination should be directed to the target of toxicity/entrapment based on information from the work history. Although specific sites and elements of the nervous system may be affected depending on the offending agent, most neurotoxic disorders are characterized by generalized rather than focal neurologic abnormalities. Laboratory toxicologic tests have limited application for the etiologic diagnosis of neurotoxic disorders, except in cases of acute poisoning and in patients exposed to neurotoxic chemicals with prolonged half-life. In most cases examination takes place after the end of exposure, when the offending chemical is no longer detectable in body fluids. Electrophysiologic studies, in particular evoked potentials, electromyography, and conduction velocities, are important to confirm the organic basis of symptoms, particularly to detect subclinical or early neurologic involvement and to reduce the number of disorders to be considered in the differential diagnoses. In general, imaging studies with computed tomography and magnetic resonance are of limited utility in the evaluation of suspected neurotoxic disorders, except for helping to exclude other causes of the patient's clinical state. Improved conditions and safer practices in the workplace have led to a gradual shift in application of neuropsychologic evaluation from the assessment of severe neurotoxic damage to the evaluation of mild subclinical disturbances, and these tests are nowadays extensively used in screening workers exposed to neurotoxicants. Tools used in the screening of large groups of workers exposed to neurotoxicants may differ from those used in the clinic. Whereas some are obviously impractical, such as physical examination, others, such as, for instance, toxicologic tests, are used for biologic monitoring of exposure to ascertain compliance with occupational exposure limits. PMID- 26563781 TI - Neuropsychologic evaluation and exposure to neurotoxicants. AB - The history of neuropsychologic assessment describes the development of a psychometric approach to neuropsychologic measurement, based on the initial clinical/theoretical approach exemplified by pioneers, who also discussed different brain functions and hypotheses for clinical exploration and treatment. Early neuropsychologic assessment practices in the USA arose out of the need to screen, diagnose, and treat World War II veterans who returned with brain injuries. Clinical testing was used to determine treatment and rehabilitation potential. Clinical psychologists had previously developed educational tests to investigate students' abilities and disabilities. Using population studies, primarily in the USA, Canada and Europe, neuropsychologists developed standardized test scores, permitting comparisons of scores based on the normal curve and evolving knowledge of brain/behavior relationships. In clinical interpretations, neuropsychologists use extensive normative data based on cognitive, mood, executive, neurologic, and motor brain functions of groups with different cultural and educational backgrounds and psychiatric illnesses. Large groups of workers can be screened with a brief neuropsychologic screening test battery to assess the psychologic status of personnel. Commonly used tests by domain are described, as well as patterns of acute and chronic neurotoxicant exposures, treatment, and rehabilitation. Future developments will relate imaging studies to neuropsychologic performance. PMID- 26563782 TI - Exposure assessment for chemical and physical agents. AB - Exposure assessment to either chemical or physical agents, as applicable, is a necessary step for both etiologic diagnosis of occupational disease and health surveillance of workers. The assessment can be carried out by measurements of concentrations in air of the substance by either fixed or personal samplers. The former give an indication of the general environment, the latter, applied near the mouth of the worker, provide personalized information. Dermal exposure (deposition) and absorption occur in the occupational setting, but their measurement is so complex that there are no routine methods and no exposure limits established. Oral exposure is accidental or associated with poor hygienic practices, is very difficult to assess, and there are no occupational exposure limits of oral intake. Also accidental injuries caused by needles or other sharp objects that might be contaminated by chemicals occur but exposure assessment in this condition is almost impossible. Exposure is also assessed by biologic monitoring that entails measurements of the substance and/or of its metabolite(s) in accessible fluids, generally urine, blood, or expired air. Biochemical changes, e.g., enzyme inhibition, associated with exposure are also measured. The results of these measurements are compared with existing limit values in order to conclude on the safety of the working conditions. Since the limit values are derived with the application of conservative assumptions, there are no fine lines between health and disease. Therefore, in the clinical setting values below the limit can be generally regarded as safe. Values above the limits should be considered in conjunction with all other information to judge on the likelihood that the disease under investigation may have been caused by exposure to the substance. PMID- 26563783 TI - The mechanisms of neurotoxicity and the selective vulnerability of nervous system sites. AB - The spatial heterogeneity of the structure, function, and cellular composition of the nervous system confers extraordinary complexity and a multiplicity of mechanisms of chemical neurotoxicity. Because of its relatively high metabolic demands and functional dependence on postmitotic neurons, the nervous system is vulnerable to a variety of xenobiotics that affect essential homeostatic mechanisms that support function. Despite protection from the neuroglia and blood brain barrier, the central nervous system is prone to attack from lipophilic toxicants and those that hijack endogenous transport, receptor, metabolic, and other biochemical systems. The inherent predilection of chemicals for highly conserved biochemical systems confers selective vulnerability of the nervous system to neurotoxicants. This chapter discusses selective vulnerability of the nervous system in the context of neuron-specific decrements (axonopathy, myelinopathy, disruption of neurotransmission), and the degree to which neuronal damage is facilitated or ameliorated by surrounding nonneural cells in both the central and peripheral nervous systems. PMID- 26563784 TI - Occupation and the risk of chronic toxic leukoencephalopathy. AB - Among the hundreds of environmental insults capable of inducing nervous system injury, a small number can produce clinically significant damage to the brain white matter. The use of magnetic resonance imaging (MRI) in affected individuals has greatly illuminated this previously obscure area of neurotoxicology. Toxic leukoencephalopathy has acute and chronic forms, in both of which cognitive dysfunction is the major clinical manifestation. Chronic toxic leukoencephalopathy (CTL) has been most thoroughly described in individuals with intense and prolonged exposure to leukotoxins, but the consequences of lesser degrees of exposure are not well understood. Rare cases of CTL have been reported in workers exposed to culpable leukotoxins, but study of this syndrome is hindered by many confounds such as uncertain level of toxin exposure, the presence of multiple toxins, vague dose-response relationship, comorbid medical or neurologic disorders, psychiatric illness, and legal issues. The risk of CTL in workers is low, although it is not possible to determine quantitative risk estimates. More knowledge can be expected with the application of advanced MRI techniques to the assessment of workers who may have been exposed to known or potential leukotoxins. Preventive measures for avoiding workplace CTL will be informed by clinical assessment involving the use of advanced neuroimaging and neuropsychologic evaluation in combination with accurate measurement of leukotoxin exposure. PMID- 26563785 TI - Neurotoxicity of solvents. AB - Worldwide, several hundred million tons of organic solvents are used annually in household, industry, and other occupational settings. Millions of workers are regularly exposed to organic solvents considered neurotoxic. Acute neurotoxicity due to high exposure of solvent is usually evident, but the nature of long-term effects, such as chronic solvent encephalopathy (CSE), has raised uncertainty even among experts. Earlier studies were criticized for their methodology, mainly epidemiologic studies or investigations of exposed groups with many possible confounders and inadequate exposure assessment. However, an increasing number of studies have been performed since, also on workers with defined CSE based on differential diagnostics. During the last decade, evidence has emerged to enable identification of CSE, a necessity for the early recognition and prevention of progression of dysfunction and disability. Selected chemicals are presented here due to their widespread use, neurotoxic potential, and ability to cause solvent encephalopathy. Constant introduction of new chemicals may introduce new hazardous chemicals or known chemicals may reveal new health effects. It is important to keep an open mind for new findings of solvent-related neurobehavioral effects. PMID- 26563786 TI - Hydrogen sulfide intoxication. AB - Hydrogen sulfide (H2S) is a hazard primarily in the oil and gas industry, agriculture, sewage and animal waste handling, construction (asphalt operations and disturbing marshy terrain), and other settings where organic material decomposes under reducing conditions, and in geothermal operations. It is an insoluble gas, heavier than air, with a very low odor threshold and high toxicity, driven by concentration more than duration of exposure. Toxicity presents in a unique, reliable, and characteristic toxidrome consisting, in ascending order of exposure, of mucosal irritation, especially of the eye ("gas eye"), olfactory paralysis (not to be confused with olfactory fatigue), sudden but reversible loss of consciousness ("knockdown"), pulmonary edema (with an unusually favorable prognosis), and death (probably with apnea contributing). The risk of chronic neurcognitive changes is controversial, with the best evidence at high exposure levels and after knockdowns, which are frequently accompanied by head injury or oxygen deprivation. Treatment cannot be initiated promptly in the prehospital phase, and currently rests primarily on supportive care, hyperbaric oxygen, and nitrite administration. The mechanism of action for sublethal neurotoxicity and knockdown is clearly not inhibition of cytochrome oxidase c, as generally assumed, although this may play a role in overwhelming exposures. High levels of endogenous sulfide are found in the brain, presumably relating to the function of hydrogen sulfide as a gaseous neurotransmitter and immunomodulator. Prevention requires control of exposure and rigorous training to stop doomed rescue attempts attempted without self-contained breathing apparatus, especially in confined spaces, and in sudden release in the oil and gas sector, which result in multiple avoidable deaths. PMID- 26563787 TI - The neurotoxicity of organochlorine and pyrethroid pesticides. AB - Organochlorine and pyrethroid compounds represent an old and a new class, respectively, of insecticides. Organochlorines such as DDT, dieldrin, or chlordecone, have been banned, primarily because of environmental issues. DDT is still used in certain countries to fight malaria-bearing mosquitoes, while lindane still finds some limited used against head lice. In contrast, pyrethroids find widespread use because of their efficacy, low environmental persistence, and relatively low mammalian toxicity. Like all insecticides, organochlorines and pyrethroids target the nervous system of insects and of nontarget species. All pyrethroids and DDT interact with the sodium channel; by keeping it open longer, they increase the likelihood of action potentials developing, thus creating a condition of hyperexcitability, whose main clinical sign is tremors. Most other organochlorines (except chlordecone), as well as certain (type II) pyrethroids, block the chloride channels of the GABA-A receptor, and cause seizures. Evidence of an association between exposure to organochlorine and pyrethroid insecticides and neurodegenerative diseases (e.g., Parkinson's disease) is weak, at best. PMID- 26563788 TI - Organophosphorus and carbamate insecticide poisoning. AB - Both organophosphorus (OP) and carbamate insecticides inhibit acetylcholinesterase (AChE), which results in accumulation of acetylcholine (ACh) at autonomic and some central synapses and at autonomic postganglionic and neuromuscular junctions. As a consequence, ACh binds to, and stimulates, muscarinic and nicotinic receptors, thereby producing characteristic features. With OP insecticides (but not carbamates), "aging" may also occur by partial dealkylation of the serine group at the active site of AChE; recovery of AChE activity requires synthesis of new enzyme in the liver. Relapse after apparent resolution of cholinergic symptoms has been reported with OP insecticides and is termed the intermediate syndrome. This involves the onset of muscle paralysis affecting particularly upper-limb muscles, neck flexors, and cranial nerves some 24-96 hours after OP exposure and is often associated with the development of respiratory failure. OP-induced delayed neuropathy results from phosphorylation and subsequent aging of at least 70% of neuropathy target esterase. Cramping muscle pain in the lower limbs, distal numbness, and paresthesiae are followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. The therapeutic combination of oxime, atropine, and diazepam is well established experimentally in the treatment of OP pesticide poisoning. However, there has been controversy as to whether oximes improve morbidity and mortality in human poisoning. The explanation may be that the solvents in many formulations are primarily responsible for the high morbidity and mortality; oximes would not be expected to reduce toxicity in these circumstances. even if given in appropriate dose. PMID- 26563789 TI - Neurotoxicity of metals. AB - Metals are frequently used in industry and represent a major source of toxin exposure for workers. For this reason governmental agencies regulate the amount of metal exposure permissible for worker safety. While essential metals serve physiologic roles, metals pose significant health risks upon acute and chronic exposure to high levels. The central nervous system is particularly vulnerable to metals. The brain readily accumulates metals, which under physiologic conditions are incorporated into essential metalloproteins required for neuronal health and energy homeostasis. Severe consequences can arise from circumstances of excess essential metals or exposure to toxic nonessential metal. Herein, we discuss sources of occupational metal exposure, metal homeostasis in the human body, susceptibility of the nervous system to metals, detoxification, detection of metals in biologic samples, and chelation therapeutic strategies. The neurologic pathology and physiology following aluminum, arsenic, lead, manganese, mercury, and trimethyltin exposures are highlighted as classic examples of metal-induced neurotoxicity. PMID- 26563790 TI - Carbon monoxide intoxication. AB - Carbon monoxide (CO) is a colorless, odorless, nonirritant gas that accounts for numerous cases of CO poisoning every year from a variety of sources of incomplete combustion of hydrocarbons. These include poorly functioning heating systems, indoor propane-powered forklifts, indoor burning of charcoal burning briquettes, riding in the back of pick-up trucks, ice skating rinks using propane-powered resurfacing machines, and gasoline-powered generators that are not in correct locations. Once CO is inhaled it binds with hemoglobin to form carboxyhemoglobin (COHb) with an affinity 200 times greater than oxygen that leads to decreased oxygen-carrying capacity and decreased release of oxygen to tissues leading to tissue hypoxia. Ischemia occurs with CO poisoning when there is loss of consciousness that is accompanied by hypotension and ischemia in the arterial border zones of the brain. Besides binding to many heme-containing proteins, CO disrupts oxidative metabolism leading to the formation of free radicals. Once hypotension and unconsciousness occur with CO poisoning, lipid peroxidation and apoptosis follow. Because COHb has a short half-life, examination of other biomarkers of CO neurotoxicity that reflect inflammation or neuronal damage has not demonstrated consistent results. The initial symptoms with CO exposure when COHb is 15-30% are nonspecific, namely, headache, dizziness, nausea, fatigue, and impaired manual dexterity. However individuals with ischemic heart disease may experience chest pain and decreased exercise duration at COHb levels between 1% and 9%. COHb levels between 30% and 70% lead to loss of consciousness and eventually death. Following resolution of acute symptoms there may be a lucid interval of 2-40 days before the development of delayed neurologic sequelae (DNS), with diffuse demyelination in the brain accompanied by lethargy, behavior changes, forgetfulness, memory loss, and parkinsonian features. Seventy-five percent of patients with DNS recover within 1 year. Neuropsychologic abnormalities with chronic CO exposure are found even when magnetic resonance imaging (MRI) and magnetic resonance spectroscopy are normal. White-matter damage in the centrum semiovale and periventricular area and abnormalities in the globus pallidus are most commonly seen on MRI following CO exposure. Though not as common, toxic or ischemic peripheral neuropathies are associated with CO exposure in humans and animals. The cornerstone for treatment for CO poisoning is 100% oxygen using a tight-fitting mask for greater than 6 hours. The indications for treatment with hyperbaric oxygen to decrease the half-life of COHb remain controversial. PMID- 26563791 TI - Extrapyramidal system neurotoxicity: animal models. AB - The central nervous system's extrapyramidal system provides involuntary motor control to the muscles of the head, neck, and limbs. Toxicants that affect the extrapyramidal system are generally clinically characterized by impaired motor control, which is usually the result of basal ganglionic dysfunction. A variety of extrapyramidal syndromes are recognized in humans and include Parkinson's disease, secondary parkinsonism, other degenerative diseases of the basal ganglia, and clinical syndromes that result in dystonia, dyskinesia, essential tremor, and other forms of tremor and chorea. This chapter briefly reviews the anatomy of the extrapyramidal system and discusses several naturally occurring and experimental models that target the mammalian (nonhuman) extrapyramidal system. Topics discussed include extrapyramidal syndromes associated with antipsychotic drugs, carbon monoxide, reserpine, cyanide, rotenone, paraquat, 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and manganese. In most cases, animals are used as experimental models to improve our understanding of the toxicity and pathogenesis of these agents. Another agent discussed in this chapter, yellowstar thistle poisoning in horses, however, represents an important spontaneous cause of parkinsonism that naturally occurs in animals. The central focus of the chapter is on animal models, especially the concordance between clinical signs, neurochemical changes, and neuropathology between animals and people. PMID- 26563792 TI - Occupational exposures and parkinsonism. AB - In recent years, the contribution of exposure to environmental toxicants has been recognized as a significant contributor to the etiopathogenesis of parkinsonism. Of these toxicants, exposure to pesticides, metals, solvents used in manufacturing processes, as well as flame-retardant chemicals used in consumer and commercial products, has received the greatest attention as possible risk factors. Related to this, individuals who are exposed to these compounds at high concentrations or for prolonged periods of time in an occupational setting appear to be one of the more vulnerable populations to these effects. Our understanding of which compounds are involved and the potential molecular pathways that are susceptible to these chemicals and may underlie the pathogenesis has greatly improved. However, there are still hundreds of chemicals that we are exposed to in the environment for which we do not have any information on their potential neurotoxicity on the nigrostriatal dopamine system. Thus, using our past accomplishments as a blueprint, future endeavors should focus on elaborating upon these initial findings in order to identify specific and relevant chemical toxicants in our environment that can impact the risk of parkinsonism and work towards a means to attenuate or abolish their effects on the human population. PMID- 26563793 TI - Tremor secondary to neurotoxic exposure: mercury, lead, solvents, pesticides. AB - Lead, mercury, solvents, and pesticide exposures are common in certain occupations and may cause nervous system dysfunction. Tremors may be the herald manifestation among a constellation of acute toxicity signs and symptoms. However, since tremors may also be the only sign on clinical presentation and since tremors also occur in other diseases, relating tremors to a specific occupational exposure can be challenging. Diagnosis of tremor etiology must be based on other findings on physical exam, laboratory results, and/or imaging. Discerning whether the tremor resulted from the occupational environment versus other etiologies requires knowledge of potential exposure sources, additional detail in history taking, and support of other health and industrial professionals. Reduction or removal from the exposure source remains the key first step in treating patients suffering from tremor that had resulted from occupational exposure toxicity. PMID- 26563794 TI - Clinical description of toxic neuropathies. AB - Toxic neuropathy, although rare, is an important consideration in the setting of a known or suspected toxic exposure in the workplace or other environment. This chapter discusses the clinical and electrodiagnostic evaluation of peripheral neuropathies, highlighting findings that direct further workup and may point to specific toxins as etiology. The difficulty of establishing causality of a toxin in relation to peripheral neuropathy is discussed; guidelines for establishing causality are presented. Examples of common industrial toxins are listed, including their typical industrial uses and their mechanisms of action in producing neuropathy. Characteristic clinical presentations of specific toxic neuropathies are highlighted with selected case studies. PMID- 26563795 TI - Neurotoxic exposure and impairment of the chemical senses of taste and smell. AB - The chemical senses of taste and smell determine the flavor of foods and beverages, guide appropriate food intake, and warn of such environmental hazards as spoiled or poisonous food, leaking natural gas, smoke, and airborne pollutants. This chapter addresses the influences of neurotoxic exposures on human chemoreception and provides basic information on the adverse influences of such exposures on rodent epithelia. The focus of the chapter is in olfaction, given dearth of empiric research on the effects of neurotoxic chemical exposures on the sense of taste, i.e., sweet, sour, bitter, salty, and savory sensations. As will be apparent from the chapter, numerous neurotoxins--many of which are encountered in industrial workplaces--alter the ability to smell, including solvents, metals, and particulate matter. The olfactory system is particularly vulnerable to such agents since its receptors are more or less directly exposed to the outside environment. Importantly, some such agents can enter the brain via the olfactory nerve or surrounding perineural spaces, bypassing the blood-brain barrier and damaging central nervous system structures and inducing pathologic processes that appear to be similar to those seen in neurodegenerative diseases such as Alzheimer's and Parkinson's. PMID- 26563796 TI - Retinal and visual system: occupational and environmental toxicology. AB - Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders. PMID- 26563797 TI - Hearing. AB - The main hazard for hearing in the workplace is noise. Organic solvents and heavy metals may increase the danger of developing occupational hearing loss, particularly in the case of co-exposure with noise. While noise produces damage predominantly to the cochlea, chemicals may be responsible for pathologic changes in both peripheral and central parts of the auditory pathway. Noise-induced hearing loss develops slowly over the years, although its progression is most dynamic during the first 10-15 years of exposure. Pure-tone audiometry indicates a bilateral sensorineural hearing loss, affecting predominantly high frequencies, with typical notch at 3-6 kHz in the early stages of the disease. Where there is co-exposure to noise and chemicals, the noise effect on hearing threshold shifts is dominant; however chemicals seem to increase the vulnerability of the cochlea to the damage by noise, particularly at its low and moderate levels. According to European Directive 2003/10/EC, the employer is obliged to implement hearing prevention programs when the A-weighted equivalent 8-hour level of noise (LAEX8 hr) exceeds 80 dB. Since chemicals may impair intelligibility of speech despite a lack of audiometric hearing threshold shift, implementation of speech audiometry, particularly speech in noise tests, is recommended in prevention programs. PMID- 26563798 TI - Mechanical stress. AB - This chapter discusses mechanical stressors that are believed to be associated with work-related musculoskeletal disorders. It starts with an introduction to work-related musculoskeletal disorders (particularly those with high incidences in workplaces, such as disorders of low back, neck/shoulder, hand/wrist, elbow, and knee) in high-risk industries, and those mechanical stressors (such as high forces, awkward postures, high repetitions, excessive contact stress, and harmful human vibrations) in workplaces that are responsible for these disorders. Quantification methods of these mechanical stressors are then discussed. Although various quantification methods such as self-report, observational technique, and direct measurement are discussed, details are focused on many of those well published observational techniques used by practitioners to assess risk levels of these mechanical stressors in jobs. These methods can quantify job mechanical stressors and provide risk level indications that can be used by practitioners to facilitate their decision making. These methods can also be used to evaluate the improvements of ergonomics interventions by comparing the risk levels quantitatively before and after the interventions. PMID- 26563799 TI - Low-back pain. AB - Low-back pain is one of the most common painful conditions experienced by humans throughout their life. Some occupational risk factors (namely, heavy manual material handling) may also contribute to the development of low-back pain: due to the high prevalence of both low-back pain and manual material handling in the adult working population, it has been estimated that low-back pain is probably the most common occupational disorder worldwide. Lifetime prevalence of low-back pain has been reported to be as high as 84%, depending on the case definition used, and no age group is spared, even children. Although low-back pain is not a lethal condition, it was estimated at the third rank among all diseases by disability-adjusted life-years in 2010 in the USA, after ischemic heart disease and chronic obstructive pulmonary disease, and at the first rank by years lived with disability. It also ranked high (13th) globally for the same year, in disability-adjusted life-years. Low-back pain is currently classified as nonspecific/specific as to putative cause and as acute (lasting less than 6 weeks), subacute (6-12 weeks), or chronic (more than 12 weeks) according to duration of symptoms. The distinction between nonspecific/specific and acute/subacute/chronic low-back pain is useful not only for epidemiologic studies, but also (mainly) for choosing the appropriate strategy for the diagnosis and treatment of the disorder. Workplace risk factors for low-back pain include manual lifting and whole-body vibration exposure. This chapter will provide an overview of modern concepts of low-back pain (in general) and will then outline some distinctive features of work-related low-back pain. PMID- 26563800 TI - Occupational mononeuropathies in industry. AB - Peripheral nerve injuries have the potential to cause significant disability and can be commonly associated with recreational and occupational activities. Acute nerve injuries are mainly related to violent trauma, while repeated mechanical trauma due to external forces or repetitive motions can produce chronic nerve compression injury. This chapter will present a narrative review of the existing evidence of the association between peripheral compressive nerve disorders and work-related risk factors. Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy in the general population and in working populations employed in manual repetitive and forceful activities. The work-relatedness of CTS is essentially based on epidemiologic evidence and the results of experimental studies showing the capability of repetitive wrist extreme postures, associated with hand-wrist forceful exertions, to increase the pressure inside the carpal tunnel and to compress the median nerve. Assembly industry, food processing and packaging, hand-arm vibrating tools, and jobs involving high repetition, high-force tasks put workers at risk for CTS. Less strong evidence exists of the association between ulnar elbow neuropathy and manual tasks or repetitive stretch on squatting and peroneal nerve neuropathy at the fibular head. Very few reports are available about the association between occupation and other compressive peripheral nerve injuries. PMID- 26563801 TI - Upper-extremity and neck disorders associated with keyboard and mouse use. AB - Musculoskeletal disorders are frequently related to computer use in the workplace. The aim of this chapter is to provide an overview of the evidence in the literature concerning the putative association between neck, shoulder, and upper-limb disorders and occupational exposure to use of a computer and its devices. We searched the scientific literature via PubMed, using specific search strategies, including substrings tailored to retrieve papers about: (1) occupational etiology; (2) computer use; and (3) different upper-limb disorders. We intended to include, in our evaluation, systematic reviews and relevant, informative papers published later on. We were able to retrieve 11 systematic reviews and 11 informative studies regarding neck, shoulder, and upper-limb disorders. There is limited/insufficient and/or inconsistent evidence indicating that computer work may be associated to neck, shoulder, or distal arm complaints. There is sufficient evidence indicating no association between carpal tunnel syndrome and computer work. There are no studies regarding the use of computers and some neck, shoulder, and upper-limb diseases, such as tennis elbow and trigger finger. Applying the general principles of ergonomics to computer work is probably the correct strategy to pursue, with the aim of maintaining office workers' well-being. PMID- 26563802 TI - Sleep deprivation due to shift work. AB - Sleep deprivation due to shift work is related to perturbation of the sleep/wake cycle, associated with the modified activity/rest pattern. This may cause a significant disruption of circadian rhythms of biologic functions, driven by the body clock located in the suprachiasmatic nuclei of the hypothalamus. Shift and night workers have to change sleep times and strategies according to their duty periods; consequently, both sleep length and quality can be considerably affected depending on the variable start and finish times on different shifts. About 10% of night and rotating shift workers, aged between 18 and 65 years, have been estimated to have a diagnosable "shift-work sleep disorder," according to the International Classification of Sleep Disorders, version 2 (ICSD-2). In the long run, this may lead to persistent and severe disturbances of sleep, chronic fatigue and psychoneurotic syndromes, besides being a risk or aggravating factor for accidents, gastrointestinal, cardiovascular, and reproductive disorders, as well as, probably, for cancer. Preventive and corrective actions deal with the organization of shift schedules according to ergonomic criteria, careful health surveillance, appropriate education and training on effective countermeasures, in particular, sleep hygiene and napping. PMID- 26563803 TI - Headache and migraine: a leading cause of absenteeism. AB - Migraine and tension-type headache, the two dominant primary headache disorders, are among the most common causes of lost work time. The population impact of both disorders is similar, but the demographics and individual impact differ. Approximately 18% of females and 6% of males have migraine in the general population. Prevalence is highest around age 40, when individuals are at the peak of their work abilities. Headaches cause substantial individual impact on work productivity and employer and societal burden from direct medical costs, lost work time, and underemployment, and, in more severe persistent headache, unemployment. The lost work time costs greatly exceed medical care costs. Chronic daily headache (15 or more headache days per month) represents a widely accepted stage of pain progression that occurs in 2-4% of the population. Treatment of headaches can be acute or preventive. The goals of acute treatment are timely alleviation of pain and associated symptoms without recurrence, the restoring of ability to function, minimizing the use of back-up and rescue medications with minimal adverse events, and providing the best cost-effective management. Migraine-preventive medications are used to decrease future attack frequency, severity, and duration, improving responsiveness to acute treatments, and improving overall function and decreasing disability. Preventing analgesic overuse that leads to chronic daily headache is another goal of using preventive treatment. Preventive medications should be considered in migraine patients reporting either 3-6 or more headache days per month, depending on how headaches impair function. PMID- 26563804 TI - Considerations for return to work following traumatic brain injury. AB - Population-based studies have demonstrated that a history positive for traumatic brain injury (TBI) can result in cognitive impairment, behavioral alterations, and pain. These outcomes can and do influence occupational function, can affect others in the workplace, and raise concerns about workplace safety upon re-entry to the workplace. Risk for long-term impairment and disability can in some cases be mitigated by assessment of capabilities relative to job duties, conservative return-to-work schedules, and, in some cases, interventions to support that return. For those in occupations at high risk for brain injury, including first responders, soldiers, and construction workers, the long-term risk of brain injury as a risk factor for neurodegenerative disease must and should inform increased concern for those with repeated injuries to the brain over the course of their lifetime and career. This chapter reviews the risks of TBI, considers factors that optimize functional recovery, and discusses potential interventions and factors that aid in return to the workplace. PMID- 26563805 TI - The complex regional pain syndrome. AB - Complex regional pain syndrome (CRPS) is the current consensus-derived name for a syndrome usually triggered by limb trauma. Required elements include prolonged, disproportionate distal-limb pain and microvascular dysregulation (e.g., edema or color changes) or altered sweating. CRPS-II (formerly "causalgia") describes patients with identified nerve injuries. CRPS-I (formerly "reflex sympathetic dystrophy") describes most patients who lack evidence of specific nerve injuries. Diagnosis is clinical and the pathophysiology involves combinations of small fiber axonopathy, microvasculopathy, inflammation, and brain plasticity/sensitization. Females have much higher risk and workplace accidents are a well-recognized cause. Inflammation and dysimmunity, perhaps facilitated by injury to the blood-nerve barrier, may contribute. Most patients, particularly the young, recover gradually, but treatment can speed healing. Evidence of efficacy is strongest for rehabilitation therapies (e.g., graded-motor imagery), neuropathic pain medications, and electric stimulation of the spinal cord, injured nerve, or motor cortex. Investigational treatments include ketamine, botulinum toxin, immunoglobulins, and transcranial neuromodulation. Nonrecovering patients should be re-evaluated for neurosurgically treatable causal lesions (nerve entrapment, impingement, infections, or tumors) and treatable potentiating medical conditions, including polyneuropathy and circulatory insufficiency. Earlier impressions that CRPS represents malingering or psychosomatic illness have been replaced by evidence that CRPS is a rare complication of limb injury in biologically susceptible individuals. PMID- 26563806 TI - Accommodation of workers with chronic neurologic disorders. AB - The ability to work is important to those with chronic neurologic disorders (CND) and to the aging workforce. Many signs and symptoms are similar in those with CND and normal aging, but may interfere with the ability to work if not appropriately accommodated. This requires the healthcare provider to recognize the specific features of the CND that interferes with work and how it can be accommodated. Review of the American with Disabilities Act and the subsequent amendment informs the healthcare provider as to what is covered under the law and how the disability can be accommodated. Overall employers want to retain qualified employees and therefore accommodating workers is beneficial to both the employee with CND and the employer. PMID- 26563807 TI - Preface. PMID- 26563808 TI - Foreword. PMID- 26563810 TI - The tendon approximator device in traumatic injuries. AB - BACKGROUND: Precise and tension-free approximation of two tendon endings is the key predictor of outcomes following tendon lacerations and repairs. We evaluate the efficacy of a new tendon approximator device in tendon laceration repairs. MATERIALS & METHODS: In a comparative study, we used our new tendon approximator device in 99 consecutive patients with laceration of 266 tendons who attend a university hospital and evaluated the operative time to repair the tendons, surgeons' satisfaction as well as patient's outcomes in a long-term follow-up. Data were compared with the data of control patients undergoing tendon repair by conventional method. RESULTS: Totally 266 tendons were repaired by approximator device and 199 tendons by conventional technique. 78.7% of patients in first group were male and 21.2% were female. In approximator group 38% of patients had secondary repair of cut tendons and 62% had primary repair. Patients were followed for a mean period of 3years (14-60 months). Time required for repair of each tendon was significantly reduced with the approximator device (2 min vs. 5.5 min, p<0.0001). After 3-4 weeks of immobilization, passive and active physiotherapy was started. Functional Results of tendon repair were identical in the two groups and were not significantly different. 1% of tendons in group A and 1.2% in group B had rupture that was not significantly different. DISCUSSION: The new nerve approximator device is cheap, feasible to use and reduces the time of tendon repair with sustained outcomes comparable to the conventional methods. PMID- 26563809 TI - Effect of low-dose mineralocorticoid receptor antagonists on metabolic profile and endothelial dysfunction in metabolic syndrome. PMID- 26563811 TI - A review of recent patents on the ASICs as a key drug target. AB - Acid-sensing ion channels (ASICs) are scattered various cells of human body. Drugs like amiloride has demonstrated nonspecific antagonism ASICs. Toxins, such as Psalmotoxin-1, have been used in animal models. There are no drugs available in the market whose action mechanism acts through these channels. We revised all patents relating to pharmaceutical formulations of applicability in ASICs. Drugs acting as antagonist in ASIC1 or ASIC3 channels seem to be the most promising targets. Patent data have suggested a variety of approaches for selective ASICs drugs, such as neuroprotective and analgesic. Studies analysis suggested that ASICs are promising targets for new drugs. PMID- 26563812 TI - Bioprospecting of Brevibacillus brevis isolated from soil. AB - It is obviously essential to find new compounds that possess industrial and medicinal importance and potential to improve the lifestyle of human population. Bioprospecting these compounds from natural resources has additional benefits since they are less toxic as well as biocompatible. In this study, Brevibacillus brevis was isolated from soil and its enzymes production, antibacterial activity and anticancer activity were assessed. The organism was found to be a promising source of amylase enzymes, antibacterial as well as anticancer compounds. PMID- 26563813 TI - Response surface optimization of the thermal acid pretreatment of sugar beet pulp for bioethanol production using Trichoderma viride and Saccharomyces cerevisiae. AB - BACKGROUND: Worldwide nowadays, relying on the second generation bioethanol from the lignocellulosic feedstock is a mandatory aim. However, one of the major drawbacks for high ethanol yield is the physical and chemical pretreatment of this kind of feedstock. As the pretreatment is a crucial process operation that modifies the lignocellulosic structure and enhances its accessibility for the high cost hydrolytic enzymes in an attempt to maximize the yield of the fermentable sugars. The objective of this work was to optimize and integrate a physicochemical pretreatment of one of the major agricultural wastes in Egypt; the sugar beet pulp (SBP) and the enzymatic saccharification of the pretreated SBP using a whole fungal cells with a separate bioethanol fermentation batch processes to maximize the bioethanol yield. METHODS AND RESULTS: The response surface methodology was employed in this study to statistically evaluate and optimize the conditions for a thermal acid pretreatment of SBP. The significance and the interaction effects of the concentrations of HCl and SBP and the reaction temperature and time were studied using a three-level central composite design of experiments. A quadratic model equation was obtained to maximize the production of the total reducing sugars. The validity of the predicted model was confirmed. The thermally acid pretreated SBP was further subjected to a solid state fermentation batch process using Trichoderma viride F94. The thermal acid pretreatment and fungal hydrolyzes were integrated with two parallel batch fermentation processes of the produced hydrolyzates using Saccharomyces cerevisiae Y39, that yielded a total of ~ 48 g/L bioethanol, at a conversion rate of ~ 0.32 g bioethanol/ g SBP. CONCLUSION: Applying the proposed integrated process, approximately 97.5 gallon of ethanol would be produced from a ton (dry weight) of SBP. PMID- 26563814 TI - The effective role of mycorrhizal symbiosis in sinking CO2 from atmosphere of mega cities. AB - An effort was made after detailed literature survey and few experiments, conducted at Laboratory conditions about the VAM fungus inoculated plants; they have large surface area and more photosynthetic rate, can assimilate more CO2, even can grow in drought condition including water deficiency and high temperature. For this purpose, a greenhouse pot experiment was conducted in which soil manifested with fungi was used and Conocarpus erectus L (common on green belt of Karachi Streets) was selected for testing the fungal engineering. Results demonstrated a well-developed strong roots system and branching pattern of shoots rather than larger surface area of leaves of the fungal engineered plant when compared with non-treated ones. The long root system indicates the stability of plant and water transport system in high temperature and low water conditions. While increased branching pattern of areal part may be directly related to an increase in net photosynthetic rates or increase CO2 absorption in the fungal inoculated plants. This investigation showed an interesting use of VAM services for technology development of root organ culture development in areas of low water availability and high temperature condition with elevated concentration of CO2. A mechanism of absorption of CO2 related with the alteration in plant bio physical metabolism is discussed in relation with phosphorus uptake under VAM inoculation. PMID- 26563815 TI - Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance. AB - BACKGROUND/OBJECTIVES: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. SUBJECTS/METHODS: Twenty two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. RESULTS: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). CONCLUSIONS: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance. PMID- 26563817 TI - [Formula: see text]Executive functions and social information processing in adolescents with severe behavior problems. AB - One tradition in research for explaining aggression and antisocial behavior has focused on social information processing (SIP). Aggression and antisocial behavior have also been studied from the perspective of executive functions (EFs), the higher-order cognitive abilities that affect other cognitive processes, such as social cognitive processes. The main goal of the present study is to provide insight into the relation between EFs and SIP in adolescents with severe behavior problems. Because of the hierarchical relation between EFs and SIP, we examined EFs as predictors of SIP. We hypothesized that, first, focused attention predicts encoding and interpretation, second, inhibition predicts interpretation, response generation, evaluation, and selection, and third, working memory predicts response generation and selection. The participants consisted of 94 respondents living in residential facilities aged 12-20 years, all showing behavior problems in the clinical range according to care staff. EFs were assessed using subtests from the Amsterdam Neuropsychological Test battery. Focused attention was measured by the Flanker task, inhibition by the GoNoGo task, and working memory by the Visual Spatial Sequencing task. SIP was measured by video vignettes and a structured interview. The results indicate that positive evaluation of aggressive responses is predicted by impaired inhibition and selection of aggressive responses by a combination of impaired focused attention and inhibition. It is concluded that different components of EFs as higher-order cognitive abilities affect SIP. PMID- 26563816 TI - Hypothalamic Effects of Tamoxifen on Oestrogen Regulation of Luteinising Hormone and Prolactin Secretion in Female Rats. AB - Oestradiol (E2) acts in the hypothalamus to regulate luteinising hormone (LH) and prolactin (PRL) secretion. Tamoxifen (TX) has been extensively used as a selective oestrogen receptor modulator, although its neuroendocrine effects remain poorly understood. In the present study, we investigated the hypothalamic effects of TX in rats under low or high circulating E2 levels. Ovariectomised (OVX) rats treated with oil, E2 or TX, or E2 plus TX, were evaluated for hormonal secretion and immunohistochemical analyses in hypothalamic areas. Both E2 and TX reduced LH levels, whereas TX blocked the E2 -induced surges of LH and PRL. TX prevented the E2 -induced expression of progesterone receptor (PR) in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), although it did not alter PR expression in OVX rats. TX blocked the E2 induction of c-Fos in AVPV neurones, consistent with the suppression of LH surge. However, TX failed to prevent E2 inhibition of kisspeptin expression in the ARC. In association with the blockade of PRL surge, TX increased the phosphorylation of tyrosine hydroxylase (TH) in the median eminence of OVX, E2 -treated rats. TX also precluded the E2 -induced increase in TH expression in the ARC. In all immunohistochemical analyses, TX treatment in OVX rats caused no measurable effect on the hypothalamus. Thus, TX is able to prevent the positive- but not negative-feedback effect of E2 on the hypothalamus. TX also blocks the effects of E2 on tuberoinfundibular dopaminergic neurones and PRL secretion. These findings further characterise the anti-oestrogenic actions of TX in the hypothalamus and provide new information on the oestrogenic regulation of LH and PRL. PMID- 26563818 TI - CO2 foam properties and the stabilizing mechanism of sodium bis(2 ethylhexyl)sulfosuccinate and hydrophobic nanoparticle mixtures. AB - In this work, we have prepared CO2-in-water foam by mixing partially hydrophobic SiO2 nanoparticles and sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and studied its properties. The observation of the appearance of the foam revealed that, with the continuous addition of AOT, the phase behavior of the SiO2 nanoparticle and the AOT mixed system transformed from that of a two-phase system of aggregated nanoparticles into that of a uniform dispersed phase. Both foaming ability and foam stability were optimized when the nanoparticles and the AOT were mixed in a proportion of 1 : 5. On the basis of our findings from measurements of the dispersion properties, including measurements of the adsorption isotherm of the surfactant on the nanoparticles, zeta potentials, interfacial tension and the three-phase contact angle, we concluded that the synergistic interactions between the SiO2 nanoparticles and the AOT led to the adsorption of nanoparticles around the bubble surface and the formation of a spatial network structure of nanoparticles in the film, thereby enhancing the mechanical strength of the bubble and improving the resistance to outside disturbances, deformation and drainage. Laser scanning confocal microscopy (LCSM) analysis of the same foams further confirmed the existence of a "viscoelastic shell" wrapped around and protecting the bubble. PMID- 26563819 TI - Utility of stereolithographic cranial biomodeling for the surgical management of a large skull base osteoma. PMID- 26563820 TI - Circulating tumor cells in breast cancer--current status and perspectives. AB - The phenomenon of tumor cell dissemination through the blood stream has been known since the 19th century. Circulating tumor cells (CTCs) may be detected in peripheral blood of patients with breast cancer and may serve as a surrogate marker for minimal residual disease. Prognostic relevance of CTCs has already been demonstrated in early and metastatic breast cancer and commercially available detection systems are currently employed in various clinical trials. Since peripheral blood is an easily accessible compartment, serial reevaluation of CTCs is possible and may contribute to better therapy monitoring. Another potential of CTCs lies in the characterization of tumor cells. Expression profiles may differ between CTCs and primary tumor, which may result in different responses to treatment. Assessment of molecular features of CTCs may be an important step for the optimization of adjuvant and metastatic systemic therapy. PMID- 26563821 TI - [Erythema palmare hereditarium (Lane's disease): Report of a paediatric case]. AB - BACKGROUND: Palmar erythema may be either congenital or acquired, hereditary or non-hereditary. Its diagnosis and management differs according to whether or not it is acquired, hereditary or associated with symptoms. Herein, we report the case of a child with hereditary palmoplantar erythema (Lane's disease). OBSERVATION: A 21/2-year-old girl consulted for palmar erythema, present since birth, predominantly on the thenar and hypothenar eminences and on the palmar aspect of her fingers. She also presented mild diffuse erythema on the soles of her feet. Both her mother and grandmother had similar signs. The girl had neither impairment nor pain linked to this erythema, and she had no associated symptoms. Physical examination was otherwise normal, as were the results of standard laboratory tests. DISCUSSION: We diagnosed Lane's disease based on the girl's hereditary erythema with autosomal dominant transmission, and the congenital and asymptomatic nature of her palmoplantar erythema. Nine publications have reported cases of Lane's disease, but this condition is probably highly under-reported. PMID- 26563822 TI - [Spontaneous cutaneous fistula of hydatid liver cysts]. AB - BACKGROUND: Spontaneous cutaneous fistula of hydatid liver cysts is a rare complication. Its genesis involves anatomic factors as well as other local factors. AIMS: An exhaustive literature review was conducted to identify the characteristics of this complication, treatment modalities and the results obtained. PATIENTS AND METHODS: An exhaustive bibliographic search was made for all articles published in French and English relating to parietal complications of hydatid liver cyst, from which we retained only those involving cases of cutaneous cyst fistulas (communicating rupture), to which we added our own case. RESULTS: Seventeen cases of cystocutaneous fistula have been reported. The reason for consultation was productive cutaneous fistula. Morphological investigations were highly evocative of the diagnosis. Thirteen patients were treated by surgery, two underwent percutaneous debridement, and two declined treatment. DISCUSSION: Cutaneous fistula constitutes a rare mode of discovery of hydatid cyst. Fistulography and CT scan are extremely useful for diagnosis. Percutaneous debridement of the hydatid cyst represents a debatable alternative to surgical therapy. PMID- 26563823 TI - Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. AB - Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism. PMID- 26563825 TI - Letter to the Editor. PMID- 26563824 TI - Changes in reproductive physiology of mangrove rivulus Kryptolebias marmoratus following exposure to environmentally relevant doses of ethinyl oestradiol. AB - Kryptolebias marmoratus exposed to 4 ng l(-1) of ethinyl oestradiol (EE2) for 30 days experienced significant changes in endogenous 17beta-oestradiol (E2) and 11 ketotestosterone (KT) and qualitative changes in gonad morphology. Both hermaphrodites and males showed a significant decrease in E2, whereas only males exhibited a significant decrease in KT. Exposure to EE2 resulted in a decrease in spermatid and spermatocyte density in males and an increase in the number of early stage oocytes in hermaphrodites. PMID- 26563827 TI - Tuning Electron-Conduction and Spin Transport in Magnetic Iron Oxide Nanoparticle Assemblies via Tetrathiafulvalene-Fused Ligands. AB - We report a strategy to coat Fe3O4 nanoparticles (NPs) with tetrathiafulvalene fused carboxylic ligands (TTF-COO-) and to control electron conduction and magnetoresistance (MR) within the NP assemblies. The TTF-COO-Fe3O4 NPs were prepared by replacing oleylamine (OA) from OA-coated 5.7 nm Fe3O4 NPs. In the TTF COO-Fe3O4 NPs, the ligand binding density was controlled by the ligand size, and spin polarization on the Fe3O4 NPs was greatly improved. As a result, the interparticle spacing within the TTF-COO-Fe3O4 NP assemblies are readily controlled by the geometric length of TTF-based ligand. The shorter the distance and the better the conjugation between the TTF's HOMO and LUMO, the higher the conductivity and MR of the assembly. The TTF-coating further stabilized the Fe3O4 NPs against deep oxidation and allowed I2-doping to increase electron conduction, making it possible to measure MR of the NP assembly at low temperature (<100 K). The TTF-COO-coating provides a viable way for producing stable magnetic Fe3O4 NP assemblies with controlled electron transport and MR for spintronics applications. PMID- 26563828 TI - 2-Amino-4-hydroxyethylaminoanisole sulfate - a coupler causing contact allergy from use in hair dyes. AB - BACKGROUND: Allergic contact dermatitis resulting from the use of permanent hair dyes is common. Approximately 100 hair dye chemicals are permitted in Europe. Hair dye ingredients may change over time, and hence new hair dye allergens should be looked for continuously. OBJECTIVES: To review positive patch test reactions to the coupler 2-amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014. METHODS: Patch test results from the Allergen Bank database for eczema patients patch tested with 2-amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014 were reviewed. RESULTS: A total of 902 dermatitis patients (154 from the dermatology department and 748 from 65 practices) were patch tested with amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014. Thirteen (1.4%) patients had a positive patch test reaction. Our results do not indicate irritant reactions. CONCLUSIONS: 2-Amino-4-hydroxyethylaminoanisole sulfate is a new but rare contact allergen. PMID- 26563826 TI - Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line. AB - Retinal ganglion cell (RGC) injury and cell death from glaucoma and other forms of optic nerve disease is a major cause of irreversible vision loss and blindness. Human pluripotent stem cell (hPSC)-derived RGCs could provide a source of cells for the development of novel therapeutic molecules as well as for potential cell-based therapies. In addition, such cells could provide insights into human RGC development, gene regulation, and neuronal biology. Here, we report a simple, adherent cell culture protocol for differentiation of hPSCs to RGCs using a CRISPR-engineered RGC fluorescent reporter stem cell line. Fluorescence-activated cell sorting of the differentiated cultures yields a highly purified population of cells that express a range of RGC-enriched markers and exhibit morphological and physiological properties typical of RGCs. Additionally, we demonstrate that aligned nanofiber matrices can be used to guide the axonal outgrowth of hPSC-derived RGCs for in vitro optic nerve-like modeling. Lastly, using this protocol we identified forskolin as a potent promoter of RGC differentiation. PMID- 26563829 TI - Smart Polymeric Nanoparticles as Emerging Tools for Imaging--The Parallel Evolution of Materials. AB - The field of imaging has developed considerably over the past decade and recent advances in the area of nanotechnology, in particular nanomaterials, have opened new opportunities. Polymeric nanoparticles are particularly interesting and a number of novel materials, characterized by stimuli-responsive characteristics and fluorescent tagging, have allowed visualization, intracellular labeling and real-time tracking. In some of the latest applications the nanoparticles have been used for imagining of tumor cells, both in vivo and ex vivo. PMID- 26563830 TI - Stochastic pacing reveals the propensity to cardiac action potential alternans and uncovers its underlying dynamics. AB - KEY POINTS: Beat-to-beat alternation (alternans) of the cardiac action potential duration is known to precipitate life-threatening arrhythmias and can be driven by the kinetics of voltage-gated membrane currents or by instabilities in intracellular calcium fluxes. To prevent alternans and associated arrhythmias, suitable markers must be developed to quantify the susceptibility to alternans; previous theoretical studies showed that the eigenvalue of the alternating eigenmode represents an ideal marker of alternans. Using rabbit ventricular myocytes, we show that this eigenvalue can be estimated in practice by pacing these cells at intervals varying stochastically. We also show that stochastic pacing permits the estimation of further markers distinguishing between voltage driven and calcium-driven alternans. Our study opens the perspective to use stochastic pacing during clinical investigations and in patients with implanted pacing devices to determine the susceptibility to, and the type of alternans, which are both important to guide preventive or therapeutic measures. ABSTRACT: Alternans of the cardiac action potential (AP) duration (APD) is a well-known arrhythmogenic mechanism. APD depends on several preceding diastolic intervals (DIs) and APDs, which complicates the prediction of alternans. Previous theoretical studies pinpointed a marker called lambdaalt that directly quantifies how an alternating perturbation persists over successive APs. When the propensity to alternans increases, lambdaalt decreases from 0 to -1. Our aim was to quantify lambdaalt experimentally using stochastic pacing and to examine whether stochastic pacing allows discriminating between voltage-driven and Ca(2+) -driven alternans. APs were recorded in rabbit ventricular myocytes paced at cycle lengths (CLs) decreasing progressively and incorporating stochastic variations. Fitting APD with a function of two previous APDs and CLs permitted us to estimate lambdaalt along with additional markers characterizing whether the dependence of APD on previous DIs or CLs is strong (typical for voltage-driven alternans) or weak (Ca(2+) -driven alternans). During the recordings, lambdaalt gradually decreased from around 0 towards -1. Intermittent alternans appeared when lambdaalt reached -0.8 and was followed by sustained alternans. The additional markers detected that alternans was Ca(2+) driven in control experiments and voltage driven in the presence of ryanodine. This distinction could be made even before alternans was manifest (specificity/sensitivity >80% for -0.4 > lambdaalt > -0.5). These observations were confirmed in a mathematical model of a rabbit ventricular myocyte. In conclusion, stochastic pacing allows the practical estimation of lambdaalt to reveal the onset of alternans and distinguishes between voltage-driven and Ca(2+) -driven mechanisms, which is important since these two mechanisms may precipitate arrhythmias in different manners. PMID- 26563832 TI - Reply to Letter to the Editor regarding "Sexual health in oral oncology: Breaking the news to patients with human papillomavirus-positive oropharyngeal cancer". PMID- 26563831 TI - Cyclic and Macrocyclic Peptides as Chemical Tools To Recognise Protein Surfaces and Probe Protein-Protein Interactions. AB - Targeting protein surfaces and protein-protein interactions (PPIs) with small molecules is a frontier goal of chemical biology and provides attractive therapeutic opportunities in drug discovery. The molecular properties of protein surfaces, including their shallow features and lack of deep binding pockets, pose significant challenges, and as a result have proved difficult to target. Peptides are ideal candidates for this mission due to their ability to closely mimic many structural features of protein interfaces. However, their inherently low intracellular stability and permeability and high in vivo clearance have thus far limited their biological applications. One way to improve these properties is to constrain the secondary structure of linear peptides by cyclisation. Herein we review various classes of cyclic and macrocyclic peptides as chemical probes of protein surfaces and modulators of PPIs. The growing interest in this area and recent advances provide evidence of the potential of developing peptide-like molecules that specifically target these interactions. PMID- 26563833 TI - Les liaisons dangereuses: resource surveillance, uranium diplomacy and secret French-American collaboration in 1950s Morocco. AB - This study explores the origins and consequences of a unique, secret, French American collaboration to prospect for uranium in 1950s Morocco. This collaboration permitted mediation between the United States and France. The appearance of France in an American-supported project for raw nuclear materials signalled American willingness to accept a new nuclear global order in which the French assumed a new, higher position as regional nuclear ally as opposed to suspicious rival. This collaboration also permitted France and the United States to agree tacitly to the same geopolitical status for the French Moroccan Protectorate, a status under dispute both in Morocco and outside it. The secret scientific effort reassured the French that, whatever the Americans might say publicly, they stood behind the maintenance of French hegemony in the centuries old kingdom. But Moroccan independence proved impossible to deny. With its foreseeable arrival, the collaboration went from seductive to dangerous, and the priority of American and French geologists shifted from finding a major uranium lode to making sure that nothing was readily available to whatever post independence interests might prove most powerful. Ultimately, the Kingdom of Morocco took a page out of the French book, using uranium exploration to assert sovereignty over a different disputed territory, its de facto colony of the Western Sahara. PMID- 26563835 TI - [Endoscopy-guided 20-G vitrectomy in severe endophthalmitis: Report of 18 cases and literature review]. AB - OBJECTIVE: To report the anatomical and functional outcomes after endoscopy guided vitrectomy in a series of cases of severe endophthalmitis. Also to identify and compare the outcomes of two different modes of clinical presentation. PATIENTS AND METHODS: Retrospective case study, single center; all patients who underwent endoscopic 20Ga vitrectomy (Endo optiks E4 system) for severe endophthalmitis were included. For each case, data were recorded for: etiology, surgical indication, preoperative and postoperative visual acuity, comorbidity factors and postoperative complications, and whether any additional surgery was performed. Two groups were distinguished according to their initial mode of presentation; results were then compared in terms of complications and visual prognosis to those found in the literature. RESULTS: Eighteen patients were included, with mean age 62+/-19years. Severe endophthalmitis was initially obvious for 8 cases (group 1). For 10 cases, disease progression had been considered unfavorable despite adequate medical treatment (group 2). There was no statistically significant difference between the two groups (P=0.55). Endophthalmitis occurred: after intravitreal injections (4 cases), after intraocular foreign body (n=2), after cataract surgery (n=5), following a trabeculectomy (n=2), after epiretinal membrane peeling (n=3), 1 case caused by a corneal infection and 1 case of endogenous leptospirosis. Mean follow-up was 13.7months. The surgical technique was a complete 20Ga vitrectomy under endoscopic visual control. The mean operative time was 70+/-27minutes. The causative organism was identified in 72% of cases in vitreous humor samples, among which 77% were gram-positive organisms. The infection was controlled in 89% of cases, and these patients have recovered useful visual acuity. CONCLUSION: The value of endoscopic visualization in ophthalmology has been proven for 30 S. aureus years, but its miniaturization enhances the current enthusiasm for the use of this instrumentation. When visualization is compromised, endoscopic guided vitrectomy is very useful and may assist the surgeon in the management of these difficult cases. Our anatomical and functional outcomes are encouraging, but we must keep in mind the poor long-term prognosis of severe endophthalmitis. PMID- 26563836 TI - [Intraoperative OCT during deep anterior lamellar keratoplasty. Difference in endothelium-Descemet's corneal thickness between donor graft and recipient cornea]. PMID- 26563834 TI - Re-adopting classical nuclear receptors by cholesterol metabolites. AB - Since the first cloning of the human estrogen receptor (ER) alpha in 1986 and the subsequent cloning of human ERbeta, there has been extensive investigation of the role of estrogen/ER. Estrogens/ER play important roles not only in sexual development and reproduction but also in a variety of other functions in multiple tissues. Selective Estrogen Receptor Modulators (SERMs) are ER lignds that act as agonists or antagonists depending on the target genes and tissues, and until recently, only synthetic SERMs have been recognized. However, the discovery of the first endogenous SERM, 27-hydroxycholesterol (27HC), opened a new dimension of ER action in health and disease. In addition to the identification of 27HC as a SERM, oxysterols have been recently demonstrated as indirect modulators of ER through interaction with the nuclear receptor Liver X Receptor (LXR) beta. In this review, the recent progress on these novel roles of oxysterols in ER modulation is summarized. PMID- 26563837 TI - Acanthamoeba keratitis associated with intracorneal hydrogel inlay. PMID- 26563838 TI - [Bilateral chronic ischemic retinopathy: A case report]. PMID- 26563839 TI - Primary orbital liposarcoma: A case report. PMID- 26563840 TI - [Orbital dermoid cysts: Clinical spectrum and outcome]. AB - INTRODUCTION: Dermoid cysts are benign congenital orbital tumors, they are classified as choristomas. Clinical manifestations vary according to location and size. MATERIALS AND METHODS: We retrospectively analyzed 43 cases of dermoid cysts surgically treated between July 1998 and March 2009. RESULTS: Mean patient age was 18.64 years. Among patients, 48.83% were male. Preseptal location was most common (41 cases). One of the two cases of intraorbital location required orbitotomy. We observed no complications or recurrence. DISCUSSION: Dermoid cysts are most often seen in young patients. The mean age of our patients was relatively high. The majority of dermoid cysts are periorbital in location. Superficial orbital dermoid cysts are more frequent, present earlier in life and are more easily identified than deep dermoid cysts. Imaging plays a major role in the management of deep orbital tumors. Complete surgical excision has remained the mainstay of treatment. CONCLUSION: Dermoid cysts are benign orbital tumors. Superficial dermoid cysts are the most common type. Deeper cysts require a more challenging diagnostic and therapeutic approach. PMID- 26563841 TI - [Acute dacryocystitis and infectious mononucleosis: An association not to be missed]. PMID- 26563842 TI - [Post-traumatic endophthalmitis]. AB - Post-traumatic endophthalmitis is a rare but serious complication of open globe injury, representing a major turning point for the patient's visual prognosis. Risk factors for this complication are lens capsule rupture, an intraocular foreign body, type of eye trauma and especially a delay in initial management of the trauma. Although Staphylococcus epidermidis is the most common organism, as in postoperative acute endophthalmitis, other microorganisms are more frequently represented and the multi-microbial involvement is common. The diagnosis can be difficult in the presence of inflammatory signs of trauma. Aside from rapid globe repair, neither preventive nor curative treatment have been well delineated. The class of antibiotics, the dosage, route of administration, as well as surgical treatment by vitrectomy remain topics of discussion. PMID- 26563843 TI - [Choroidal osteoma]. PMID- 26563844 TI - Frailty, Frailty Components, and Oral Health: A Systematic Review. AB - A systematic review was conducted to assess the relationship between frailty or one of its components and poor oral health. A search strategy was developed to identify articles related to the research question in the PubMed, EMBASE, Cochrane, LILACS, and SciELO databases that were published in English, Spanish, or Brazilian Portuguese from 1991 to July 2013. Thirty-five studies were identified, and 12 met the inclusion criteria, seven of which were cross sectional and five were cohort studies. Of the 12 articles, five (41.7%) were rated good and seven (58.3%) as fair quality. The published studies applied different oral health and frailty criteria measures. Variations in definitions of outcome measures and study designs limited the ability to draw strong conclusions about the relationship between frailty or prefrailty and poor oral health. None of the studies that were evaluated longitudinally showed whether poor oral health increases the likelihood of developing signs of frailty, although the studies suggest that there may be an association between frailty and oral health. More longitudinal studies are needed to better understand the relationship between frailty and oral health. PMID- 26563845 TI - Triarylboron-Based Fluorescent Organic Light-Emitting Diodes with External Quantum Efficiencies Exceeding 20 . AB - Triarylboron compounds have attracted much attention, and found wide use as functional materials because of their electron-accepting properties arising from the vacant p orbitals on the boron atoms. In this study, we design and synthesize new donor-acceptor triarylboron emitters that show thermally activated delayed fluorescence. These emitters display sky-blue to green emission and high photoluminescence quantum yields of 87-100 % in host matrices. Organic light emitting diodes using these emitting molecules as dopants exhibit high external quantum efficiencies of 14.0-22.8 %, which originate from efficient up-conversion from triplet to singlet states and subsequent efficient radiative decay from singlet to ground states. PMID- 26563846 TI - The prevalence and correlates of undiagnosed HIV among Australian gay and bisexual men: results of a national, community-based, bio-behavioural survey. AB - INTRODUCTION: Gay and bisexual men (GBM) with undiagnosed HIV are believed to contribute disproportionately to HIV transmission in Australia but national prevalence estimates have been lacking. METHODS: From November 2013 to November 2014, we recruited men at gay venues and events in six Australian states and territories. Of 7291 survey participants, 3071 men also provided an oral fluid sample for testing and decided whether to receive their test results or not. We calculated raw and population-weighted prevalence estimates and identified associations with undiagnosed infection using logistic regression. RESULTS: Of 3071 participants, 213 men tested HIV-positive (6.9%, 95% confidence interval [CI] 6.0 to 7.8%), of whom 19 (8.9%, 95% CI 5.8 to 13.5%) were previously undiagnosed. After weighting for the size of the gay and bisexual male population in each state or territory, national HIV prevalence was estimated to be 7.2% (95% CI 6.3 to 8.1), of which 9.1% (95% CI 6.0 to 13.6%) were estimated to be undiagnosed. Compared with HIV-negative participants, men with undiagnosed HIV were more likely to report meeting partners at sex venues, using antiretroviral drugs as pre-exposure prophylaxis, condomless anal intercourse with casual partners, using party drugs for sex, injecting drugs and using amyl nitrite, crystal methamphetamine or gamma hydroxybutyrate in the six months prior to the survey. DISCUSSION: The results indicate that the prevalence of undiagnosed HIV is relatively low among Australian GBM but is higher among men who report riskier sex and drug practices. CONCLUSIONS: The results underline the importance of targeted HIV prevention and frequent testing for men at increased risk of infection. PMID- 26563847 TI - The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample. AB - The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes. PMID- 26563848 TI - Genome-wide association analysis and differential expression analysis of resistance to Sclerotinia stem rot in Brassica napus. AB - Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum. PMID- 26563849 TI - An evaluation of alirocumab for the treatment of hypercholesterolemia. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in lipoprotein metabolism, mainly by modulating LDL receptor activity. Alirocumab is a fully human IgG1 monoclonal antibody that binds PCSK9, increases the number of LDL receptors and decreases the levels of LDL cholesterol. The efficacy of alirocumab has been evaluated in more than 6000 subjects with primary hypercholesterolemia; in Phase III trials, alirocumab consistently reduced LDL cholesterol up to 62% with every 2 weeks dosing compared with placebo and up to 36% compared with ezetimibe. Two doses, 75 and 150 mg, have been developed to propose a tailored approach in the treatment of hypercholesterolemic patients not controlled by maximally tolerated lipid-lowering therapy. Alirocumab was generally well-tolerated, with an acceptable safety profile. The ongoing ODYSSEY OUTCOMES trial will provide definitive evidence on the effect of alirocumab on cardiovascular morbidity and mortality and complementary data on the long-term safety and tolerability. Moreover, a cost-effectiveness analysis would be useful to determine the appropriate price of alirocumab. PMID- 26563850 TI - Efficacy and safety of pilocarpine for radiation-induced xerostomia in patients with head and neck cancer: A systematic review and meta-analysis. AB - BACKGROUND: Pilocarpine has been used widely in the treatment of dry mouth and glaucoma. In this review, the authors assessed the efficacy and safety of pilocarpine for patients with head and neck cancer who have radiation-induced xerostomia. TYPES OF STUDIES REVIEWED: The authors conducted a systematic search including meta-analyses and randomized controlled trials in the following databases: MEDLINE, Embase, Cochrane Library, and Science Citation Index Expanded. The primary outcome was the severity of xerostomia (measured using visual analog scale [VAS] scores). Adverse events were other outcomes of interest. The authors performed meta-analyses where appropriate. The authors used the Cochrane Collaboration's tool for assessing risk of bias to assess the quality of the study. RESULTS: The authors identified 6 studies (including 752 patients in total). The results of a meta-analysis of 3 articles showed that pilocarpine was associated with a 12-point increase in VAS score (mean difference, 12.00; 95% confidence interval [CI], 1.93-22.08; P = .02) and higher rates of adverse events compared with placebo in terms of sweating (odds ratio [OR], 3.71; 95% CI, 2.34-5.86; P < .00001). There were no differences in rhinitis (OR, 1.21; 95% CI, 0.68-2.16; P = .52) and nausea (OR, 1.44; 95% CI, 0.83-2.49; P = .19). CONCLUSIONS AND PRACTICAL IMPLICATIONS: On the basis of the best available evidence, the results of this meta-analysis provide evidence that pilocarpine offers statistically significant clinical benefits for the symptomatic treatment of radiation-induced xerostomia in patients with head and neck cancer. However, the authors of this systematic review found the best available evidence in the meta-analysis in 3 studies, 1 of which showed no effect. The authors of this systematic review suggest that these patients take 5 milligrams of pilocarpine 3 times daily, and that there is need for further study. PMID- 26563851 TI - Nobel Prize for artemisinin brings phytotherapy into the spotlight. PMID- 26563852 TI - Anomalous Aortic Origin of Coronary Arteries in the Young: Echocardiographic Evaluation With Surgical Correlation. AB - OBJECTIVES: This study sought to compare findings from institutional echocardiographic reports with imaging core laboratory (ICL) review of corresponding echocardiographic images and operative reports in 159 patients with anomalous aortic origin of a coronary artery (AAOCA). The study also sought to develop a "best practice" protocol for imaging and interpreting images in establishing the diagnosis of AAOCA. BACKGROUND: AAOCA is associated with sudden death in the young. Underlying anatomic risk factors that can cause ischemia related events include coronary arterial ostial stenosis, intramural course of the proximal coronary within the aortic wall, interarterial course, and potential compression between the great arteries. Consistent protocols for diagnosing and evaluating these features are lacking, potentially precluding the ability to risk stratify patients based on evidence and plan surgical strategy. METHODS: For a prescribed set of anatomic AAOCA features, percentages of missing data in institutional echocardiographic reports were calculated. For each feature, agreement among institutional echocardiographic reports, ICL review of images, and surgical reports was evaluated using the weighted kappa statistic. An echocardiographic imaging protocol was developed heuristically to reduce differences between institutional reports and ICL review. RESULTS: A total of 13%, 33%, and 62% of echocardiograms were missing images enabling diagnosis of intra-arterial course, proximal intramural course, and high ostial takeoff, respectively. There was poor agreement between institutional reports and ICL review for diagnosis of origin of coronary artery, interarterial course, intramural course, and acute angle takeoff (kappa = 0.74, 0.11, -0.03, 0.13, respectively). Surgical findings were also significantly different from those of reports, and to a lesser extent ICL reviews. The resulting protocol contains technical recommendations for imaging each of these features. CONCLUSIONS: Poor agreement between institutional reports and ICL review for AAOCA suggests need for an imaging protocol to permit evidence-based risk stratification and surgical planning. Even then, delineation of echocardiographic details in AAOCA will remain imperfect. PMID- 26563853 TI - Management Implications for Anomalous Aortic Origin of Coronary Arteries. PMID- 26563854 TI - Interobserver Agreement of the Echocardiographic Diagnosis of LV Hypertrabeculation/Noncompaction. AB - OBJECTIVES: The aim of the study was to assess interobserver agreement (IOA) between 3 observers from 2 laboratories. BACKGROUND: IOA of left ventricular hypertrabeculation/noncompaction (LVHT) in adults has only been studied within single echocardiographic laboratories. METHODS: Echocardiographic recordings with and without LVHT were selected and anonymized. The "not-LVHT" cases were matched for age and systolic function. Each observer reviewed the recordings, blinded to the initial diagnosis and the other observers' results. Pre-defined criteria for LVHT were: 1) >3 prominent trabeculae at end-diastole, distinct from papillary muscles, false tendons, or aberrant bands; 2) a noncompacted part of a 2-layered myocardial structure formed by these trabeculations; 3) a ratio of >2:1 of noncompacted to compacted layer at end-systole; and 4) perfusion of the intertrabecular spaces from the ventricular cavity. IOA was estimated using the kappa measure of concordance. RESULTS: Cine-loops of 100 patients (42 women, ages 16 to 92 years), 50 from each center, and 51 with LVHT as the initial diagnosis, were reviewed. The left ventricular end-diastolic diameter was 32 to 78 mm, and ejection fraction, 4% to 88%. The observers agreed about presence (n = 29) or absence (n = 36) of LVHT and disagreed in 35 cases. Agreement was higher among the 2 observers from the same laboratory (kappa 0.793 [95% confidence interval (CI): 0.672 to 0.915]) than from different laboratories (kappa 0.628 [95% CI: 0.472 to 0.784], kappa 0.669 [95% CI: 0.521 to 0.818]). The observers agreed with the initial report of LVHT-presence in 53% and of absence in 67%. By reviewing the discordant cases, consensus was achieved about LVHT presence (n = 8) or absence (n = 16); in 11 cases, the diagnosis remained questionable. Discordance was due to poor image quality, lack of views in different apical planes, aberrant bands and chordae tendineae, abnormally sized or inserting papillary muscles, and localized calcifications of the endocardium. CONCLUSIONS: IOA was substantial for diagnosing LVHT. However, even the application of pre-defined criteria yielded disagreement in 35% of cases; and after mutual review, there were still 11% questionable cases. PMID- 26563855 TI - When and How to Agree in Disagreeing on the Diagnosis of Noncompaction by Echocardiography? PMID- 26563856 TI - Regional Heterogeneity of LV Wall Thickness. PMID- 26563857 TI - The Whole Is Greater Than the Sum of its Parts: Combining CT Angiography and Highly Sensitive Troponin in the Diagnostic Work-Up of Patients With Acute Chest Pain. PMID- 26563858 TI - Risk Prediction Using CACS in Younger Populations: Theory or Valid Practice? PMID- 26563859 TI - Clinical Impact of OCT Findings During PCI: The CLI-OPCI II Study. AB - OBJECTIVES: The goal of this study was to assess the clinical impact of optical coherence tomography (OCT) findings during percutaneous coronary intervention (PCI). BACKGROUND: OCT provides unprecedented high-definition visualization of plaque/stent structures during PCI; however, the impact of OCT findings on outcome remains undefined. METHODS: In the context of the multicenter CLI-OPCI (Centro per la Lotta contro l'Infarto-Optimisation of Percutaneous Coronary Intervention) registry, we retrospectively analyzed patients undergoing end procedural OCT assessment and compared the findings with clinical outcomes. RESULTS: A total of 1,002 lesions (832 patients) were assessed. Appropriate OCT assessment was obtained in 98.2% of cases and revealed suboptimal stent implantation in 31.0% of lesions, with increased incidence in patients experiencing major adverse cardiac events (MACE) during follow-up (59.2% vs. 26.9%; p < 0.001). In particular, in-stent minimum lumen area <4.5 mm(2) (hazards ratio [HR]: 1.64; p = 0.040), dissection >200 MUm at the distal stent edge (HR: 2.54; p = 0.004), and reference lumen area <4.5 mm(2) at either distal (HR: 4.65; p < 0.001) or proximal (HR: 5.73; p < 0.001) stent edges were independent predictors of MACE. Conversely, in-stent minimum lumen area/mean reference lumen area <70% (HR: 1.21; p = 0.45), stent malapposition >200 MUm (HR: 1.15; p = 0.52), intrastent plaque/thrombus protrusion >500 MUm (HR: 1.00; p = 0.99), and dissection >200 MUm at the proximal stent edge (HR: 0.83; p = 0.65) were not associated with worse outcomes. Using multivariable Cox hazard analysis, the presence of at least 1 significant criterion for suboptimal OCT stent deployment was confirmed as an independent predictor of MACE (HR: 3.53; 95% confidence interval: 2.2 to 5.8; p < 0.001). CONCLUSIONS: Suboptimal stent deployment defined according to specific quantitative OCT criteria was associated with an increased risk of MACE during follow-up. PMID- 26563860 TI - How to Decipher OCT After PCI. PMID- 26563862 TI - Functional Evaluation of Coronary Disease by CT Angiography. AB - In recent years, several technical developments in the field of cardiac computed tomography (CT) have made possible the extraction of functional information from an anatomy-based examination. Several different lines have been explored and will be reviewed in the present paper, namely: 1) myocardial perfusion imaging; 2) transluminal attenuation gradients and corrected coronary opacification indexes; 3) fractional flow reserve computed from CT; and 4) extrapolation from atherosclerotic plaque characteristics. In view of these developments, cardiac CT has the potential to become in the near future a truly 2-in-1 noninvasive evaluation for coronary artery disease. PMID- 26563861 TI - Value of Exercise ECG for Risk Stratification in Suspected or Known CAD in the Era of Advanced Imaging Technologies. AB - Exercise stress electrocardiography (ExECG) is underutilized as the initial test modality in patients with interpretable electrocardiograms who are able to exercise. Although stress myocardial imaging techniques provide valuable diagnostic and prognostic information, variables derived from ExECG can yield substantial data for risk stratification, either supplementary to imaging variables or without concurrent imaging. In addition to exercise-induced ischemic ST-segment depression, such markers as ST-segment elevation in lead aVR, abnormal heart rate recovery post-exercise, failure to achieve target heart rate, and poor exercise capacity improve risk stratification of ExECG. For example, patients achieving >=10 metabolic equivalents on ExECG have a very low prevalence of inducible ischemia and an excellent prognosis. In contrast, cardiac imaging techniques add diagnostic and prognostic value in higher-risk populations (e.g., poor functional capacity, diabetes, or chronic kidney disease). Optimal test selection for symptomatic patients with suspected coronary artery disease requires a patient-centered approach factoring in the risk/benefit ratio and cost effectiveness. PMID- 26563863 TI - High-Risk Plaque Features on Coronary CT Angiography. PMID- 26563864 TI - Longitudinal Strain and Type 1 Diabetes Mellitus: Are We on the Wrong Track? PMID- 26563865 TI - Reply: Longitudinal Strain and Type 1 Diabetes Mellitus: Are We on the Wrong Track? PMID- 26563866 TI - A Picture is Worth a Thousand Questions: Is OCT Ready for Routine Clinical Use? PMID- 26563867 TI - Association between breakfast consumption and educational outcomes in 9-11-year old children - CORRIGENDUM. PMID- 26563868 TI - Recent advances in the application of hydrophilic interaction chromatography for the analysis of biological matrices. AB - Hydrophilic interaction chromatography (HILIC) is being increasingly used for the analysis of hydrophilic compounds in biological matrices. The complexity of biological samples demands adequate sample preparation procedures, specifically adjusted for HILIC analyses. Currently, most bioanalytical assays are performed on bare silica and ZIC-HILIC columns. Trends in HILIC for bioanalysis include smaller particle sizes and miniaturization of the analytical column. For complex biological samples, multidimensional techniques can separate and identify more compounds than 1D separations. The high volatility of the mobile phase, the added separation power and high sensitivity make MS the detection method of choice for bioanalysis using HILIC, although other detectors such as evaporative light scattering detection, charged aerosol detection and nuclear magnetic resonance have been reported. PMID- 26563871 TI - Genomic Correlates to the Newly Proposed Grading Prognostic Groups for Prostate Cancer. AB - Recommendations by the International Society of Urologic Pathology and 2016 World Health Organization blue book propose the use of a five-tiered prostate cancer (PCa) grading system. The five prognostic grade groupings (PGGs) ranging from 1 to 5 are defined as Gleason grades <= 6, 3 + 4, 4 + 3, 8, and > 8, respectively. Recent work suggests that each group is associated with a distinct risk of biochemical PCa recurrence. In this study, we sought genomic support for PGGs using whole-exome and whole-genome sequencing data for 426 clinically localized PCas treated by radical prostatectomy. After adjustment for tumor purity for the sequencing data, we observed a significant frequency increase in genomic amplifications and deletions (p = 0.013) and in nonsynonymous point mutations (p = 0.008) with increasing risk group. Interestingly, PGG1 (low risk) was entirely haploid, whereas PGG2-5 exhibited increasing polyploidy frequency. Principal component analysis of genomic profiles revealed that PGG1, PGG2, and PGG3 represent distinct classes, but PGG4 and PGG5 exhibit genomic similarity. Together, these observations for the largest PCa genomic data set to date provide support for increasing genomic alterations with increasing PGG. This is the first genomic correlation of the PGG system. Future work will need to explore the clinical utility of PGGs in prospective studies with long-term follow-up. PATIENT SUMMARY: Gleason grading for prostate cancer provides important information for guiding clinical care. A new proposal by leading pathologists favors translating Gleason grades into five risk categories. In this study, a comprehensive analysis of the largest genomic data set on prostate cancer to date, we demonstrate molecular support for this new five-tiered system. PMID- 26563870 TI - Dietary Fatty Acid Metabolism is Affected More by Lipid Level than Source in Senegalese Sole Juveniles: Interactions for Optimal Dietary Formulation. AB - This study analyses the effects of dietary lipid level and source on lipid absorption and metabolism in Senegalese sole (Solea senegalensis). Juvenile fish were fed 4 experimental diets containing either 100 % fish oil (FO) or 25 % FO and 75 % vegetable oil (VO; rapeseed, linseed and soybean oils) at two lipid levels (~8 or ~18 %). Effects were assessed on fish performance, body proximate composition and lipid accumulation, activity of hepatic lipogenic and fatty acid oxidative enzymes and, finally, on the expression of genes related to lipid metabolism in liver and intestine, and to intestinal absorption, both pre- and postprandially. Increased dietary lipid level had no major effects on growth and feeding performance (FCR), although fish fed FO had marginally better growth. Nevertheless, diets induced significant changes in lipid accumulation and metabolism. Hepatic lipid deposits were higher in fish fed VO, associated to increased hepatic ATP citrate lyase activity and up-regulated carnitine palmitoyltransferase 1 (cpt1) mRNA levels post-prandially. However, lipid level had a larger effect on gene expression of metabolic (lipogenesis and beta oxidation) genes than lipid source, mostly at fasting. High dietary lipid level down-regulated fatty acid synthase expression in liver and intestine, and increased cpt1 mRNA in liver. Large lipid accumulations were observed in the enterocytes of fish fed high lipid diets. This was possibly a result of a poor capacity to adapt to high dietary lipid level, as most genes involved in intestinal absorption were not regulated in response to the diet. PMID- 26563869 TI - Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin. AB - Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7 overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance. PMID- 26563872 TI - [Neonatal neuroblastoma complicated with a threatening tumoral hepatomegaly treated by irradiation: No sequel 20 years later]. AB - In this article, we report the case of a newborn who presented a life-threatening hepatomegaly with respiratory distress at 12 days of life, complicating a metastatic neuroblastoma. Low-dose liver radiotherapy was performed in emergency in order to decompress. Chemotherapy has also been delivered due to a tumoral relapse 1 month after radiotherapy. After a follow-up of 20 years, this young woman is still in complete remission, with no long-term sequelae. PMID- 26563873 TI - [Therapeutic outcomes of medulloblastoma in Casablanca from 2000 to 2012]. AB - PURPOSE: To describe the therapeutic results, with the aim to contribute to improving the care of patients with medulloblastoma. PATIENTS AND METHODS: A retrospective study of 69 cases of medulloblastoma collected in the university hospital Ibn Rochd of Casablanca between 2000 and 2012. RESULTS: Fifty-three children with an average age of 9 years and 16 adults with an average age of 32.4 years were included in the study. Thirty-seven children and eight adults suffered from a high-risk tumour. The radiotherapy was received by all patients with a mean dose of 36 Gy to the whole brain and 54 Gy in the posterior fossa. All patients in the paediatric group and 10 patients in the adult group received concomitant chemotherapy, 44 children and four adults received adjuvant chemotherapy. Tumour recurrence was observed in 17 children after a mean follow up period of 38 months. These recurrences were observed in five adults after a mean follow-up period of 42 months. The posterior fossa was the main site of relapses. Overall survival was 77.7% for the children and 61% for the adults. Overall survival was better (70% versus 25%) when the interval between radiotherapy and surgery was less than 40 days in the paediatric group. The recurrence rate was significantly higher for the high-risk group: 41% versus 13% for the standard risk. In the adult group, overall survival differences according to the risk group were significant (100% for the standard risk versus 37.5% for the high risk). CONCLUSION: The overall survival and recurrences rate obtained are encouraging. The risk group and time between surgery and radiotherapy were prognostic factors with significant impact on survival depending on the age group. We recommend reducing these times to improve therapeutic results. PMID- 26563874 TI - Burden of waterpipe smoking and chewing tobacco use among women of reproductive age group using data from the 2012-13 Pakistan Demographic and Health Survey. AB - BACKGROUND: Despite the general decline in cigarette smoking, use of alternative forms of tobacco has increased particularly in developing countries. Waterpipe (WP) and Chewing Tobacco (CT) are two such alternative forms, finding their way into many populations. However, the burden of these alternative forms of tobacco and their socio demographic determinants are still unclear. We assessed the prevalence of WP and CT use among women of reproductive age group in Pakistan. METHODS: Data from the most recent Pakistan Demographic and Health Survey 2012-13 (n = 13,558) was used for this analysis. Information obtained from ever married women, aged between 15 and 49 years were analyzed using two separate data subgroups; exclusive WP smokers (total n = 12,995) and exclusive CT users (total n = 12,771). Univariate and Multivariate logistic regression analyses were conducted and results were reported as crude and adjusted Odds Ratio with 95% confidence intervals. RESULTS: Prevalence of WP smoking and CT were 4% and 2%, respectively. After multivariate adjustments, ever married women who were: older than 35 years (OR; 4.68 95% CI, 2.62-8.37), were poorest (OR = 4.03, 95% CI 2.08 7.81), and had no education (OR = 9.19, 95% CI 5.10-16.54), were more likely to be WP smokers. Similarly, ever married women who were: older than 35 years (OR = 3.19, 95% CI 1.69-6.00), had no education (OR = 4.94, 95% CI 2.62-9.33), were poor (OR = 1.64, 95% CI 1.07-2.48) and had visited health facility in last 12 months (OR = 1.81, 95% CI 1.22-2.70) were more likely to be CT users as well. CONCLUSION: Older women with lower socio-economic profile were more likely to use WP and CT. Focused policies aiming towards reducing the burden of alternate forms of tobacco use among women is urgently needed to control the tobacco epidemic in the country. PMID- 26563876 TI - Breathing exercises for adults with asthma. AB - Asthma is a common long-term condition that remains poorly controlled in many people despite the availability of pharmacological interventions, evidence-based treatment guidelines and care pathways.(1) There is considerable public interest in the use of non-pharmacological approaches for the treatment of asthma.(2) A survey of people with asthma reported that many have used complementary and alternative medicine, often without the knowledge of their clinical team.(3) Such interventions include breathing techniques, herbal products, homeopathy and acupuncture. The role of breathing exercises within the management of asthma has been controversial, partly because early claims of effectiveness were exaggerated.(4) UK national guidance and international guidelines on the management of asthma have included the option of breathing exercise programmes as an adjuvant to pharmacological treatment.(5,6) Here we discuss the types of breathing exercises used and review the evidence for their effectiveness. PMID- 26563875 TI - Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes. AB - INTRODUCTION: Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA) and have a potent chondrolytic effect. However, little is known about the cellular receptors and signaling mechanisms that are mediated by FN-fs. We investigated whether the 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) regulates cartilage catabolism via the Toll-like receptor (TLR)-2 signaling pathway in human chondrocytes. METHODS: Small interfering RNA was used to knock down TLR-2 and myeloid differentiation factor 88 (MyD88). TLR-2 was overexpressed in chondrocytes transfected with a TLR-2 expression plasmid. The expression levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were analyzed using quantitative real-time reverse transcription polymerase chain reactions, immunoblotting, or enzyme-linked immunosorbent assay. The effect of TLR-2 on 29-kDa FN-f-mediated signaling pathways was investigated by immunoblotting. RESULTS: TLR-2, TLR-3, TLR-4, and TLR-5 mRNA were significantly overexpressed in OA cartilage compared with normal cartilage, whereas no significant difference of TLR-1 mRNA expression was found. 29-kDa FN-f significantly increased TLR-2 expression in human chondrocytes in a dose- and time-dependent manner. Knockdown of TLR-2 or MyD88, the latter a downstream adaptor of TLR-2, significantly inhibited 29-kDa FN-f-induced MMP production at the mRNA and protein levels. Conversely, TLR-2 overexpression led to enhanced MMP production by 29-kDa FN-f. In addition, TLR-2 knockdown apparently inhibited 29 kDa FN-f-mediated activation of phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and p38, but not of c-Jun N-terminal kinase or extracellular signal-regulated kinase. Exposure to synovial fluid (SF) from affected joints of patients with OA elevated MMP-1, MMP-3, and MMP-13 expression markedly in primary chondrocytes without reducing cell viability. However, TLR-2 knockdown in chondrocytes significantly suppressed SF induced MMP induction. CONCLUSIONS: Our data demonstrate that the MyD88-dependent TLR-2 signaling pathway may be responsible for 29-kDa FN-f-mediated cartilage catabolic responses. Our results will enhance understanding of cartilage catabolic mechanisms driven by cartilage degradation products, including FN-f. The modulation of TLR-2 signaling activated by damage-associated molecular patterns, including 29-kDa FN-f, is a potential therapeutic strategy for the prevention of cartilage degradation in OA. PMID- 26563878 TI - Addendum: management of anogenital warts. PMID- 26563877 TI - Ivermectin cream for rosacea. AB - Rosacea is a chronic facial skin disease that mainly occurs in people aged over 30 years. It is common, with an estimated incidence of 1.7 per 1,000 person-years in general practice in the UK.(1,2) Rosacea can cause embarrassment, anxiety, low self-esteem and lack of confidence.(3) A new topical treatment has become available for the treatment of one of the clinical subtypes of rosacea. Ivermectin 10mg/g (1%) cream (Soolantra-Galderma) has received marketing authorisation for the treatment of inflammatory lesions of papulopustular rosacea in adults.(4) Here we review the safety and effectiveness of ivermectin cream in the treatment of rosacea and assess how it compares with standard therapies. PMID- 26563879 TI - Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11beta-HSD1 Deficient Mice. AB - Mice deficient in the glucocorticoid-regenerating enzyme 11beta-HSD1 resist age related spatial memory impairment. To investigate the mechanisms and pathways involved, we used microarrays to identify differentially expressed hippocampal genes that associate with cognitive ageing and 11beta-HSD1. Aged wild-type mice were separated into memory-impaired and unimpaired relative to young controls according to their performance in the Y-maze. All individual aged 11beta-HSD1 deficient mice showed intact spatial memory. The majority of differentially expressed hippocampal genes were increased with ageing (e.g. immune/inflammatory response genes) with no genotype differences. However, the neuronal-specific transcription factor, Npas4, and immediate early gene, Arc, were reduced (relative to young) in the hippocampus of memory-impaired but not unimpaired aged wild-type or aged 11beta-HSD1-deficient mice. A quantitative reverse transcriptase-polymerase chain reaction and in situ hybridisation confirmed reduced Npas4 and Arc mRNA expression in memory-impaired aged wild-type mice. These findings suggest that 11beta-HSD1 may contribute to the decline in Npas4 and Arc mRNA levels associated with memory impairment during ageing, and that decreased activity of synaptic plasticity pathways involving Npas4 and Arc may, in part, underlie the memory deficits seen in cognitively-impaired aged wild-type mice. PMID- 26563880 TI - [Formula: see text]Working memory and behavioral inhibition in boys with ADHD: An experimental examination of competing models. AB - Working memory (WM) and behavioral inhibition impairments have garnered significant attention as candidate core features, endophenotypes, and/or associated neurocognitive deficits of attention-deficit/hyperactivity disorder (ADHD). The relationship between ADHD-related WM and inhibition deficits remains relatively unclear, however, with inferences about the constructs' directional relationship stemming predominantly from correlational research. The current study utilized a dual-task paradigm to experimentally examine the relationship between ADHD-related WM and behavioral inhibition deficits. A total of 31 boys (15 ADHD and 16 typically developing [TD]) aged 8-12 years completed WM (1-back and 2-back), behavioral inhibition (stop-signal task [SST]), and dual-condition (1-back/SST and 2-back/SST) experimental tasks. Children with ADHD exhibited significant, large-magnitude WM deficits for the 1-back condition but were not significantly different from children in the TD group for the 2-back, 1-back/SST, and 2-back/SST conditions. Children with ADHD also exhibited significant inhibition deficits for the SST, 1-back/SST, and 2-back/SST conditions, but the within-group effect was not significant. The findings suggest that ADHD-related stop-signal demands are upstream, or compete for, resources involved in controlled-focused attention and/or other central executive (CE), WM processes. PMID- 26563881 TI - Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin. AB - The evolutionarily conserved mechanistic target of rapamycin (mTOR) forms two functionally distinct complexes, mTORC1 and mTORC2. mTORC1, consisting of mTOR, raptor, and mLST8 (GbetaL), is sensitive to rapamycin and thought to control autonomous cell growth in response to nutrient availability and growth factors. mTORC2, containing the core components mTOR, mLST8, Rictor, mSIN1, and Protor1/2 is largely insensitive to rapamycin. mTORC2 specifically senses growth factors and regulates cell proliferation, metabolism, actin rearrangement, and survival. Dysregulation of mTOR signaling often occurs in a variety of human malignant diseases, rendering it a crucial and validated target in cancer treatment. However, the effectiveness of rapamycin as single-agent therapy is suppressed, in part, by the numerous strong mTORC1-dependent negative feedback loops. Although preclinical and clinical studies of ATP-competitive mTOR inhibitors that target both mTORC1 and mTORC2 have shown greater effectiveness than rapalogs for cancer treatment, the mTORC1 inhibition-induced negative feedback activation of PI3- K/PDK1 and Akt (Thr308) may be sufficient to promote cell survival. Recent cancer biology studies indicated that mTORC2 is a promising target, since its activity is essential for the development of a number of cancers. These studies provide a rationale for developing inhibitors specifically targeting mTORC2, which do not perturb the mTORC1- dependent negative feedback loops and have a more acceptable therapeutic window. This review summarizes the present understanding of mTORC2 signaling and functions, especially tumorigenic functions, highlighting the current status and future perspectives for targeting mTORC2 in cancer treatment. PMID- 26563882 TI - Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models. AB - Despite the enormous number of anticancer drugs presently available in the clinic, treatment failure due to drug resistance is very frequent. The identification of mechanisms of resistance to different drugs is necessary, in order to identify ways to prevent and circumvent such resistance. Indeed, the identification of novel therapeutic targets to overcome cancer drug resistance remains one of the major challenges in drug discovery and development. The methods employed to identify drug resistance mechanisms and novel therapeutic targets depend greatly on the establishment of cancer drug resistant cell lines. The establishment of such drug resistant cell lines is laborious and time consuming and various different approaches have been described. This manuscript reviews the methodologies that have been used to create cancer drug resistant cell lines and to identify their mechanisms of resistance. In addition, this review highlights the most frequent drug resistance mechanisms found in cancer cells. PMID- 26563883 TI - Cytochrome P450 2W1 (CYP2W1) in Colorectal Cancers. AB - Cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1) is a newly identified monooxygenase enzyme that is expressed specifically in tumor tissues and during fetal life. Particularly, high expression of CYP2W1 was observed in up to 60% of colorectal cancers and its expression correlated with poor survival. CYP2W1 has been shown to metabolize various endogenous substrates including lysophospholipids and several procarcinogens, such as polycyclic aromatic hydrocarbon. The specific substrate for CYP2W1, however, is currently unknown. Due to its tumor-specific expression and its unique catalytic activities in colorectal cancers, CYP2W1 was deemed as an interesting target in colorectal cancer therapy. This review sought to summarize the current understanding of the CYP2W1 biology and biochemistry, its genetic polymorphisms and cancer risk, and its implication as a tumor-specific diagnostic and therapeutic target. PMID- 26563884 TI - Potential Therapeutic Approaches for the Treatment of Acute Myeloid Leukemia with AML1-ETO Translocation. AB - BACKGROUND: Twenty percent of patients with Acute Myeloid Leukemia (AML) carry a translocation between chromosomes 21 and chromosome 8 resulting in the formation of a chimeric oncoprotein AML1-ETO. The patients with this translocation although have a favourable prognosis, but the 5-year survival is only about 50%. It is anticipated that identification of novel therapeutic targets in t(8;21) positive AML will lead to treatment options that improve patient survival. AREAS COVERED: The oncoprotein and the proteins required to maintain its stability and functionality are the first obvious therapeutic targets. Further, newer technologies like combining gene expression and DNA occupancy profiling assays, gene expression-based high-throughput screening, etc have led to identification of proteins or pathways that are required by AML1-ETO for leukemogenesis and the agents that modulate these proteins to be considered good candidates for targeted molecular therapy. Various FDA approved drugs and secondary metabolites derived from traditional medicinal plants have been shown to possess anti-proliferative effect on t(8:21) harboring leukemic cell lines. CONCLUSION: In order to improve the therapeutic regime for AML patients with t(8;21), efforts are required to translate the success achieved in identification of potent candidates for targeted therapy into clinical setup in the best possible combination. PMID- 26563885 TI - Biochemical measures and frailty in people with intellectual disabilities. AB - INTRODUCTION: People with intellectual disabilities (ID) are earlier frail than people in the general population. Although this may be explained by lifelong unfavourable social, psychological and clinical causes, underlying physiological pathways might be considered too. Biological measures can help identify pathophysiological pathways. Therefore, we examined the association between frailty and a range of serum markers on inflammation, anaemia, the metabolic system, micronutrients and renal functioning. METHODS: Participants (n = 757) with borderline to severe ID (50+) were recruited from three Dutch ID care and support services. RESULTS: Frailty was measured with a frailty index, a measure based on the accumulation of deficits. Linear regression analyses were performed to identify associations between frailty and biochemical measures independent of age, gender, level of ID and the presence of Down syndrome. Frailty appears associated with inflammation (IL-6 and CRP), anaemia, metabolic markers (glucose, cholesterol and albumin) and renal functioning (cystatin-C and creatinine). DISCUSSION: These results are in line with results observed in the general population. Future research needs to investigate the causal relation between biochemical measures and frailty, with a special focus on inflammation and nutrition. Furthermore, the possibility to screen for frailty using biochemical measures needs to be used. PMID- 26563886 TI - The impact of indoor air quality and contaminants on respiratory health of older people living in long-term care residences in Porto. AB - BACKGROUND: persons who are 65 years or older often spend an important part of their lives indoors thus adverse indoor climate might influence their health status. OBJECTIVE: to evaluate the influence of indoor air quality and contaminants on older people's respiratory health. DESIGN: cross-sectional study. SETTING: 21 long-term care residences (LTC) in the city of Porto, Portugal. SUBJECTS: older people living in LTC with >=65 years old. METHODS: the Portuguese version of BOLD questionnaire was administered by an interviewer to older residents able to participate (n = 143). Indoor air contaminants (IAC) were measured twice, during winter and summer in 135 areas. Mixed effects logistic regression models were used to study the association between the health questionnaire results and the monitored IAC, adjusted for age, smoking habits, gender and number of years living in the LTC. RESULTS: cough (23%) and sputum (12%) were the major respiratory symptoms, and allergic rhinitis (22%) the main self-reported illness. Overall particulate matter up to 2.5 micrometres in size median concentration was above the reference levels both in winter and summer seasons. Peak values of particulate matter up to 10 micrometres in size (PM10), total volatile organic compounds, carbon dioxide, bacteria and fungi exceeded the reference levels. Older people exposed to PM10 above the reference levels demonstrated higher odds of allergic rhinitis (OR = 2.9, 95% CI: 1.1-7.2). CONCLUSION: high levels of PM10 were associated with 3-fold odds of allergic rhinitis. No association was found between indoor air chemical and biological contaminants and respiratory symptoms. PMID- 26563887 TI - Associations of metabolic, inflammatory and oxidative stress markers with total morbidity and multi-morbidity in a large cohort of older German adults. AB - BACKGROUND: imbalances in metabolic, inflammatory and redox homeostasis play an important role in the leading theories of age-related morbidity, but no large scale epidemiological study has been conducted so far assessing their associations with total morbidity and multi-morbidity in the same model. METHODS: analyses were conducted in 2,547 participants of an established population-based cohort study from Germany. The participants' median age was 70 years (range: 57 84) and 51.9% were women. End points were total somatic morbidity and multi morbidity, assessed by the Cumulative Illness Rating Scale-Geriatric version. RESULTS: overall, 251 study participants had multi-morbidity (9.9%). Except for the redox marker 'total thiol levels of proteins', all other assessed metabolic (obesity, diabetes, dyslipidaemia and hypertension), inflammatory (C-reactive protein) and oxidative stress markers (derivatives of reactive oxygen metabolites) were significantly associated with total somatic morbidity and multi morbidity if assessed individually. If modelled jointly, effect estimates were attenuated but remained statistically significant for the outcome 'total morbidity' and for low weight, obesity, insufficiently controlled diabetes and derivatives of reactive oxygen metabolites with respect to the outcome 'multi morbidity'. CONCLUSIONS: results from this large sample of older adults support hypotheses that relate imbalances in metabolic, inflammatory and redox homeostasis to age-related morbidity. Despite over adjustment for closely related metabolic, inflammatory and oxidative stress conditions in the full model, independent associations of the markers with total morbidity and/or multi morbidity were observed. Therefore, adverse metabolic, inflammatory and oxidative stress conditions may all play important roles in the pathogenesis of age-related morbidity, which should be investigated further in future longitudinal studies. PMID- 26563888 TI - Ortner's syndrome: a rare cause of sudden hoarseness in the older person. PMID- 26563889 TI - Continuous monitoring of emergency admissions of older care home residents to hospital. AB - BACKGROUND: evidence from inspection programmes suggest that the quality of care provided by individual care homes for older people is very variable. Aside from periodic inspection, there is limited information that is routinely collected and can be used to monitor quality. OBJECTIVES: to describe a method for using routine hospital data on admissions of older people as means for monitoring quality of care within a care home. To explore how this might be applied and used. METHODS: we linked hospital admissions to care homes using postcode matching and analysed hospital admission data as a time series, using the Cumulative Sum (CUSUM) technique to detect unusually high rates of admission. RESULTS: if we develop the CUSUM so that the number of times it falsely signals a high rate of admissions is limited to a rate of 0.1% per year, the chances of successfully detecting a doubling of the admission rate within 2 years will range from 48% for the smaller homes to 96% for the larger homes. CONCLUSION: monitoring tools using data on admissions to hospital are both possible and feasible, particularly for the larger homes. However, due to data limitations, users need to be careful about how they interpret triggers and thus ensure follow up is appropriate. Some of the problems caused by using routine national data can be overcome if care homes used their own information for local monitoring. PMID- 26563890 TI - Does trauma type relate to posttraumatic growth after war? A pilot study of young Iraqi war survivors living in Turkey. AB - Positive personal gain after adverse life events and traumas is known as posttraumatic growth (PTG). Several factors are suggested to promote PTG after stressful events, including type of trauma, in addition to younger age and female gender. Although conflicting findings exist, studies suggest that there may be less growth associated with personal traumas (i.e., physical or sexual assault, accidents) and more growth associated with shared traumas (i.e., disasters, loss). We examined whether certain types of war-related traumas are associated with more PTG in a sample of 203 Iraqi students living in Turkey who had experienced severe war-related traumatic events. They were assessed in group sessions, using a self-report battery that included the Post-Traumatic Growth Inventory and War Trauma Questionnaire. War experiences were categorized into three types of trauma: trauma to self, trauma to loved ones, and adversity. Growth was measured by the Turkish version of the Post-Traumatic Growth Inventory. Adversity-type events positively predicted growth, whereas trauma to self predicted growth negatively. Males and females showed a different pattern of relationship with growth. Correlations of growth with younger age and adversity observed in females were not seen in males. Our results show that different trauma types may lead to differing levels of growth, and this difference may be more pronounced when gender is taken into account. PMID- 26563891 TI - Cognitive assessment of refugee children: Effects of trauma and new language acquisition. AB - Each year, approximately 60,000 children of refugee background are resettled in Western countries. This paper reviews the effects of the refugee experience on cognitive functioning. The distinctive influences for these children include exposure to traumatic events and the need to acquire a new language, factors that need to be considered to avoid overdiagnosis of learning disorders and inappropriate educational placements. Prearrival trauma, psychological sequelae of traumatic events, developmental impact of trauma, and the quality of family functioning have been found to influence cognitive functioning, learning, and academic performance. In addition, the refugee child may be semiproficient in several languages, but proficient in none, whilst also trying to learn a new language. The influence that the child's limited English proficiency, literacy, and school experience may have on academic and test performance is demonstrated by drawing on the research on refugees' English language acquisition, as well as the more extensive literature on bilingual English language learners. Implications for interventions are drawn at the level of government policy, schools, and the individual. The paper concludes with the observation that there is a major need for longitudinal research on refugee children's learning and academic performance and on interventions that will close the academic gap, thereby enabling refugee children to reach their educational potential. PMID- 26563893 TI - The clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza A (H3N2) epidemic: the uniqueness of HPIV-3 mimicking influenza A. AB - During influenza epidemics, influenza-like illnesses (ILIs) viruses cocirculate with influenza strains. If positive, rapid influenza diagnostic tests (RIDTs) identify influenza A/B, but false-negative RIDTs require retesting by viral polymerase chain reaction (PCR). Patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. In adults, the most useful laboratory abnormalities in influenza include relative lymphopenia, monocytosis, and thrombocytopenia. Lymphocyte:monocyte (L:M) ratios may be even more useful. L:M ratios <2 have been used as a surrogate marker for influenza, but there are no longitudinal data on L:M ratios in hospitalized adults with viral ILIs. During the 2015 influenza A (H3N2) epidemic at our hospital, we reviewed our experience with L:M ratios in 37 hospitalized adults with non-influenza viral ILIs. In hospitalized adults with non-influenza A ILIs, the L:M ratios were >2 with human metapneumovirus (hMPV), rhinoviruses/enteroviruses (R/E), and respiratory syncytial virus (RSV), but not human parainfluenza virus type 3 (HPIV-3), which had L:M ratios <2. HPIV-3, like influenza, was accompanied by L:M ratios <2, mimicking influenza A (H3N2). In influenza A admitted adults, L:M ratios <2 did not continue for >3 days, whereas with HPIV-3, L:M ratios <2 persisted for >3 days of hospitalization. PMID- 26563892 TI - BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by L-NAME/thiopental combination. AB - AIM: We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157. MAIN METHODS: (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 MUg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 MUg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental. KEY FINDINGS: (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 MUg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats. SIGNIFICANCE: Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157). PMID- 26563894 TI - Raman spectroscopy-based identification of nosocomial outbreaks of the clonal bacterium Escherichia coli. AB - DNA-based techniques are frequently used to confirm the relatedness of putative outbreak isolates. These techniques often lack the discriminatory power when analyzing closely related microbes such as E. coli. Here the value of Raman spectroscopy as a typing tool for E. coli in a clinical setting was retrospectively evaluated. PMID- 26563895 TI - The mystery of the fourth clone: comparative genomic analysis of four non typeable Streptococcus pneumoniae strains with different susceptibilities to optochin. AB - Optochin-resistant pneumococci can be rarely caught in clinical microbiology laboratories because of the routine identification of all such strains as viridans group non-pneumococci. We were lucky to find four non-typeable Streptococcus pneumoniae clones demonstrating the different susceptibilities to optochin: one of them (Spn_13856) was resistant to optochin, while the other three (Spn_1719, Spn_27, and Spn_2298) were susceptible. Whole genome nucleotide sequences of these strains were compared to reveal the differences between the optochin-resistant and optochin-susceptible strains. Two adjacent genes coding maltose O-acetyltransferase and uridine phosphorylase which were presented in the genomes of all optochin-susceptible strains and missed in the optochin-resistant strain were revealed. Non-synonymous substitutions in 14 protein-coding genes were discovered, including the Ala49Ser mutation in the C-subunit of the F0 part of the ATP synthase rotor usually associated with pneumococcal optochin resistance. Modeling of a process of optochin interaction with the F0 part of the ATP synthase rotor indicates that the complex of optochin with "domain C" composed by wild-type C-subunits is more stable than the same complex composed of Ala49Ser mutant C-subunits. PMID- 26563896 TI - Prevalence of cytomegalovirus, and its effect on the expression of inducible and endothelial nitric oxide synthases in Fallopian tubes collected from women with and without ectopic pregnancy. AB - To measure the prevalence of cytomegalovirus (CMV) infection in ectopic pregnancy (EP) and its effect on the expression of inducible and endothelial nitric oxide synthases (iNOS, eNOS) by Fallopian tubes (FT) bearing an EP. This was a prospective case-control study. Blood and tubal samples were collected from 84 Eps and 51 controls (20 total abdominal hysterectomy (TAH) during the luteal phase and another 31 tubal ligations). CMV IgM and IgG antibodies were measured by ELISA, and an IVD CE PCR kit was used to detect CMV in the FTs. iNOS and eNOS were measured by immunohistochemistry and quantitative RT-PCR in FTs obtained from CMV-positive EP (n = 12), and the results were compared with those obtained from CMV-negative EP (n = 11) and TAH (n = 8). The frequencies of CMV IgM (51.2 % vs 17.6 %), IgG (77.4 % vs 52.9 %) or both antibodies (41.6 % vs 11.7 %) were significantly higher in EP compared with control. CMV was more common by PCR in FTs from EP (21.4 %) than controls (5.9 %). Twelve women from the PCR positive EP cases (66.6 %) were also simultaneously positive for both CMV IgM & IgG antibodies and had higher expression of eNOS and iNOS at the protein and gene levels compared with negative EP and TAH. Tubal infection with CMV may lead to EP by increasing the production of endothelial and inducible NOS by the FT epithelial cells. Further studies are required to illustrate the role of CMV in the pathogenesis of EP. PMID- 26563897 TI - VCS parameters of neutrophils, monocytes and lymphocytes may indicate local bacterial infection in cancer patients who accepted cytotoxic chemotherapeutics. AB - Bacterial infections increased greatly in cancer patients who accepted cytotoxic chemotherapeutics. VCS parameters of neutrophils were reported to be an indicator for acute bacterial infection accompanied by increased WBC counts. Here we explored the possibility of VCS parameters of neutrophils, monocytes and lymphocytes in indicating the local bacterial infection in cancer patients. A total of 310 cancer patients and 90 healthy controls were retrospectively analyzed, and 190 of them were diagnosed as acute local bacterial infection. The VCS parameters acquired from a Beckman Coulter LH750 haematology analyzer were investigated to determine which VCS parameters could indicate local bacterial infection in cancer patients with leucopenia caused by cytotoxic agents. VCS parameters of cancer patients were significantly affected by infection. For diagnosing bacterial infection of cancer patients, the best single indicator was mean monocyte light scatter (MMS) with a sensitivity of 95.12 % and a specificity of 58.82 % and the area under the curve (AUC) was 0.792. A combination of the following five parameters: mean neutrophil volume (MNV), MMS, mean lymphocyte conductivity (MLC), mean lymphocyte light scatter (MLS) and neutrophil volume distribution width (NDW) could provide a better index in diagnosing bacterial infection than any single parameter (sensitivity 75.8 %, specificity 64.72 %, AUC 0.763). Taking WBC counts into consideration, VCS parameters could better indicate bacterial infection for cancer patients with abnormal WBC level than that with normal WBC level. Aside from neutrophils, the VCS of monocytes and lymphocytes were also ideal indicators for bacterial infection. The combination of VCS parameters could increase the sensitivity, specificity and accuracy of diagnosis of cancer patients. PMID- 26563898 TI - Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry. AB - Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin(r) Outcomes Registry and Experience (EU CORE(SM)) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections. PMID- 26563899 TI - Comparison of the BD MAX(r) Enteric Bacterial Panel assay with conventional diagnostic procedures in diarrheal stool samples. AB - Although infectious diarrhea is one of the most predominant diseases around the world, the identification of the causative microorganism is still challenging. The aim of this study was the evaluation of the BD MAX(r) Enteric Bacterial Panel assay in comparison to conventional diagnostic procedures concerning the detection of the enteric pathogens Salmonella spp., Campylobacter spp., Shigella spp., and Shiga toxin-producing Escherichia coli. For this purpose, 971 prospectively collected stool samples were evaluated. Utilization of the BD MAX Enteric Bacterial Panel elevated the overall detection rate from 5.26 % to 8.06 %. The positive percent agreement of the BD MAX Enteric Bacterial Panel assay and stool culture or enzyme immunoassay was 0.97 for Campylobacter spp., 0.75 for Salmonella spp., 1.00 for Shigella spp., and 0.88 for Shiga toxins. Furthermore, a negative percent agreement of 0.98 for Campylobacter spp., 0.99 for Salmonella spp., 0.99 for Shigella spp., and 0.99 for Shiga toxins has been demonstrated. This study highlighted the superior detection rate of molecular assays compared to conventional diagnostic procedures. PMID- 26563900 TI - Above-the-knee replantation in a child: a case report with a 24-year follow-up. AB - Replantation of an amputated limb is generally contraindicated in crushing and traction injuries. Injury to muscle tissue and skin also creates difficulties in coverage, and bony fractures may shorten limb length which can impede lower extremity function. Numerous cases have been reported on the successful replantation of the lower limb in children; however, review of previous English literature has documented only very few replantation at the thigh level, and those with severe crushing injury resulted in subsequent amputation. We report a case of successful thigh-level replantation in a 3-year-old child who sustained a crushing-traction type of injury with a follow-up of 24 years. After the replantation, early and late complications developed but these were successfully managed. On her last visit, the patient had pain-free ambulation without assistance, had intact protective sensation distal to the injury, and was very satisfied with the outcome. Replantation of the lower limb in children with crushing or avulsion type of injuries is still a worthwhile procedure. However, both the patient and the family should be aware that multiple surgeries may be needed to accommodate to long-term complications such as joint stiffness, scar contractures, and limb length discrepancies. PMID- 26563901 TI - Variations in Crystalline Structures and Electrical Properties of Single Crystalline Boron Nitride Nanosheets. AB - We report the studies of (1) the basic mechanism underlying the formation of defect-free, single crystalline boron nitride nanosheets (BNNSs) synthesized using pulsed laser plasma deposition (PLPD) technique, (2) the variation in the crystalline structure at the edges of the hexagonal boron nitride (h-BN) nanosheets, and (3) the basic electrical properties related to the BNNSs tunneling effect and electrical breakdown voltage. The nanoscale morphologies of BNNSs are characterized using scanning electron microscope (SEM) and high resolution transmission electron microscope (HRTEM). The results show that each sample consisted of a number of transparent BNNSs that partially overlapped one another. Varying the deposition duration yielded different thicknesses of sample but did not affect the morphology, structure, and thickness of individual BNNSs pieces. Analysis of the SEM and HRTEM data revealed changes in the spatial period of the B3-N3 hexagonal structures and the interlayer distance at the edge of the BNNSs, which occurred due to the limited number of atomic layers and was confirmed further by x-ray diffraction (XRD) study. The experimental results clearly indicate that the values of the electrical conductivities of the super thin BNNSs and the effect of temperature relied strongly on the direction of observation. PMID- 26563902 TI - Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal. AB - BACKGROUND: Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. METHODS: We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed >=1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. RESULTS: After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). CONCLUSION: In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates. PMID- 26563903 TI - Legume proteomics: Progress, prospects, and challenges. AB - Legumes are the major sources of food and fodder with strong commercial relevance, and are essential components of agricultural ecosystems owing to their ability to carry out endosymbiotic nitrogen fixation. In recent years, legumes have become one of the major choices of plant research. The legume proteomics is currently represented by more than 100 reference maps and an equal number of stress-responsive proteomes. Among the 48 legumes in the protein databases, most proteomic studies have been accomplished in two model legumes, soybean, and barrel medic. This review highlights recent contributions in the field of legume proteomics to comprehend the defence and regulatory mechanisms during development and adaptation to climatic changes. Here, we attempted to provide a concise overview of the progress in legume proteomics and discuss future developments in three broad perspectives: (i) proteome of organs/tissues; (ii) subcellular compartments; and (iii) spatiotemporal changes in response to stress. Such data mining may aid in discovering potential biomarkers for plant growth, in general, apart from essential components involved in stress tolerance. The prospect of integrating proteome data with genome information from legumes will provide exciting opportunities for plant biologists to achieve long-term goals of crop improvement and sustainable agriculture. PMID- 26563904 TI - Development of repeatable arrays of proteins using immobilized DNA microplate (RAPID-M) technology. AB - BACKGROUND: Protein microarrays have enormous potential as in vitro diagnostic tools stemming from the ability to miniaturize whilst generating maximum evaluation of diagnostically relevant information from minute amounts of sample. In this report, we present a method known as repeatable arrays of proteins using immobilized DNA microplates (RAPID-M) for high-throughput in situ protein microarray fabrication. The RAPID-M technology comprises of cell-free expression using immobilized DNA templates and in situ protein purification onto standard microarray slides. RESULTS: To demonstrate proof-of-concept, the repeatable protein arrays developed using our RAPID-M technology utilized green fluorescent protein (GFP) and a bacterial outer membrane protein (OmpA) as the proteins of interest for microarray fabrication. Cell-free expression of OmpA and GFP proteins using beads-immobilized DNA yielded protein bands with the expected molecular sizes of 27 and 30 kDa, respectively. We demonstrate that the beads immobilized DNA remained stable for at least four cycles of cell-free expression. The OmpA and GFP proteins were still functional after in situ purification on the Ni-NTA microarray slide. CONCLUSION: The RAPID-M platform for protein microarray fabrication of two different representative proteins was successfully developed. PMID- 26563905 TI - Properties of compressible elastica from relativistic analogy. AB - Kirchhoff's kinetic analogy relates the deformation of an incompressible elastic rod to the classical dynamics of rigid body rotation. We extend the analogy to compressible filaments and find that the extension is similar to the introduction of relativistic effects into the dynamical system. The extended analogy reveals a surprising symmetry in the deformations of compressible elastica. In addition, we use known results for the buckling of compressible elastica to derive the explicit solution for the motion of a relativistic nonlinear pendulum. We discuss cases where the extended Kirchhoff analogy may be useful for the study of other soft matter systems. PMID- 26563906 TI - Efficacy of an exercise intervention for employees with work-related fatigue: study protocol of a two-arm randomized controlled trial. AB - BACKGROUND: The aim of the current study is to evaluate the efficacy of an exercise intervention to reduce work-related fatigue. Exercise is a potentially effective intervention strategy to reduce work-related fatigue, since it may enhance employees' ability to cope with work stress and it helps to detach from work. However, based on available research, no clear causal inferences regarding its efficacy can be made. This RCT therefore investigates whether exercise is effective in reducing work-related fatigue, and in improving other indicators of employees' mental and physical well-being and performance. METHODS/DESIGN: A two arm parallel trial will be conducted. Participants (N = 108) who experience high levels of work-related fatigue will be randomized at a 1:1 ratio to a 6-week exercise intervention or wait list (control). The exercise intervention consists of three one-hour low-intensity outdoor running sessions a week. Each week, two sessions take place in a group under supervision of a trainer, and one session is completed individually. The running sessions will be carried out during leisure time. The primary outcome is work-related fatigue. Secondary outcomes include work ability, self-efficacy, sleep quality, cognitive functioning, and aerobic fitness. These data will be collected at pre-intervention, post-intervention, and at 6 weeks and 12 weeks after the intervention. In addition, weekly measures of employees' well-being, and exercise activities (i.e. type, frequency, and duration) and experiences (i.e. pleasure, effort, and detachment) will be collected during the intervention period. DISCUSSION: This study will compare an exercise intervention to a wait list. This enables us to examine the effect of exercise on work-related fatigue compared to the natural course of these symptoms. As such, this study contributes to a better understanding of the causal link between exercise and work-related fatigue. If the intervention is proven effective, the results could provide a basis for future 'effectiveness' trials in which the (implementation of the) intervention can be investigated among a broader defined population in a less standardized way, eventually leading to better evidence-based policies and practices to employees, employers, health practitioners, and policy makers concerning the effect of exercise on work related fatigue. TRIAL REGISTRATION: NTR5034. Registered 10 March 2015. PMID- 26563907 TI - FLT3-ITD mutations do not impact the outcome of patients allografted with partial T-cell depleted grafts for AML with normal cytogenetics in first complete remission. PMID- 26563908 TI - Imprinting bulk amorphous alloy at room temperature. AB - We present investigations on the plastic deformation behavior of a brittle bulk amorphous alloy by simple uniaxial compressive loading at room temperature. A patterning is possible by cold-plastic forming of the typically brittle Hf-based bulk amorphous alloy through controlling homogenous flow without the need for thermal energy or shaping at elevated temperatures. The experimental evidence suggests that there is an inconsistency between macroscopic plasticity and deformability of an amorphous alloy. Moreover, imprinting of specific geometrical features on Cu foil and Zr-based metallic glass is represented by using the patterned bulk amorphous alloy as a die. These results demonstrate the ability of amorphous alloys or metallic glasses to precisely replicate patterning features onto both conventional metals and the other amorphous alloys. Our work presents an avenue for avoiding the embrittlement of amorphous alloys associated with thermoplastic forming and yields new insight the forming application of bulk amorphous alloys at room temperature without using heat treatment. PMID- 26563909 TI - Percutaneous treatment of left main and non-left main bifurcation coronary lesions using drug-eluting stents. AB - Current evidence and guidelines support the use of the single-stent technique as the default treatment strategy for the treatment of coronary bifurcations. For the single-stent technique, routine final kissing balloon inflation is not recommended, unless side branch ostial stenosis is assumed to be functionally significant. The double-stent technique is still a viable option for bifurcations with large and severely diseased side branches. Due to the unique features of bifurcation anatomy and bifurcation stenting techniques, all deployed stents should be optimized by postdilation, kissing balloon inflation and/or the proximal optimization technique, regardless of the stenting technique used. Intravascular ultrasound can guide preimplantation decision-making and postimplantation optimization by providing information on reference diameter, plaque burden and distribution, and stent underexpansion and malapposition. PMID- 26563910 TI - Brachycephalic airway syndrome: a comparative study between pugs and French bulldogs. AB - OBJECTIVE: To compare clinical features of brachycephalic airway syndrome and long-term surgical outcomes between pugs and French bulldogs and evaluate the influence of laryngeal collapse. METHODS: This retrospective study included 72 dogs that underwent wedge rhinoplasty and folded flap palatoplasty for brachycephalic airway syndrome. Epidemiological data, clinical signs, postoperative complications and owners' responses to a questionnaire at least six months after surgery were compared between pugs and French bulldogs. Spearman's rank correlation tests were used for associating laryngeal collapse with age and respiratory signs before and after surgery. RESULTS: On the basis of the results of the owners' questionnaires (available in 52/72 dogs), French bulldogs presented with lower activity levels and more severe digestive signs than pugs. Owners perceived clinical improvement in 88 . 5% of all dogs. The grades of respiratory and digestive signs were not different between the breeds in the long term follow-up, and the grade of laryngeal collapse did not influence the grade of respiratory signs or surgical outcome. CLINICAL SIGNIFICANCE: Surgical treatment resulted in improved clinical signs in pugs and French bulldogs with brachycephalic airway syndrome, with a high owner satisfaction rate. There were no correlations between the severity of laryngeal collapse and overall respiratory signs or prognosis. PMID- 26563912 TI - Comparison of otolith and scale readings for age and growth estimation of common dentex Dentex dentex. AB - Three methods of age estimation were compared for Dentex dentex. Based on sectioned otoliths, scales appeared to be relevant only up to 5 years and whole otoliths up to 12 years. The maximum estimated age was 36 years, which constitutes to date the oldest age reported. PMID- 26563911 TI - Microporous Polymers from a Carbazole-Based Triptycene Monomer: Synthesis and Their Applications for Gas Uptake. AB - Two kinds of novel organic microporous polymers TCPs (TCP-A and TCP-B) were prepared by two cost-effective synthetic strategies from the monomer of tricarbazolyltriptycene (TCT). Their structure and properties were characterized by FT-IR, solid (13) C NMR, powder XRD, SEM, TEM, and gas absorption measurements. TCP-B displayed a high surface area (1469 m(2) g(-1) ) and excellent H2 storage (1.70 wt % at 1 bar/77 K) and CO2 uptake abilities (16.1 wt % at 1 bar/273 K), which makes it a promising material for potential application in gas storage. PMID- 26563914 TI - Polyboramines for Hydrogen Release: Polymers Containing Lewis Pairs in their Backbone. AB - The one-step polycondensation of diamines and diboranes triggered by the in situ deprotonation of the diammonium salts and concomitant reduction of bisboronic acids leads to the assembly of polymer chains through multiple Lewis pairing in their backbone. These new polyboramines are dihydrogen reservoirs that can be used for the hydrogenation of imines and carbonyl compounds. They also display a unique dihydrogen thermal release profile that is a direct consequence of the insertion of the amine-borane linkages in the polymeric backbone. PMID- 26563913 TI - Characterization of Interstrand DNA-DNA Cross-Links Using the alpha-Hemolysin Protein Nanopore. AB - Nanopore-based sensors have been studied extensively as potential tools for DNA sequencing, characterization of epigenetic modifications such as 5 methylcytosine, and detection of microRNA biomarkers. In the studies described here, the alpha-hemolysin protein nanopore embedded in a lipid bilayer was used for the detection and characterization of interstrand cross-links in duplex DNA. Interstrand cross-links are important lesions in medicinal chemistry and toxicology because they prevent the strand separation that is required for read out of genetic information from DNA in cells. In addition, interstrand cross links are used for the stabilization of duplex DNA in structural biology and materials science. Cross-linked DNA fragments produced unmistakable current signatures in the nanopore experiment. Some cross-linked substrates gave irreversible current blocks of >10 min, while others produced long current blocks (10-100 s) before the double-stranded DNA cross-link translocated through the alpha-hemolysin channel in a voltage-driven manner. The duration of the current block for the different cross-linked substrates examined here may be dictated by the stability of the duplex region left in the vestibule of the nanopore following partial unzipping of the cross-linked DNA. Construction of calibration curves measuring the frequency of cross-link blocking events (1/tauon) as a function of cross-link concentration enabled quantitative determination of the amounts of cross-linked DNA present in samples. The unique current signatures generated by cross-linked DNA in the alpha-HL nanopore may enable the detection and characterization of DNA cross-links that are important in toxicology, medicine, and materials science. PMID- 26563915 TI - Vitamin D status and its determinants during autumn in children at northern latitudes: a cross-sectional analysis from the optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. AB - Sufficient summer/autumn vitamin D status appears important to mitigate winter nadirs at northern latitudes. We conducted a cross-sectional study to evaluate autumn vitamin D status and its determinants in 782 Danish 8-11-year-old children (55 degrees N) using baseline data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study, a large randomised controlled trial. Blood samples and demographic and behavioural data, including 7-d dietary recordings, objectively measured physical activity, and time spent outdoors during school hours, were collected during September-November. Mean serum 25-hydroxyvitamin D (25(OH)D) was 60.8 (sd 18.7) nmol/l. Serum 25(OH)D levels <=50 nmol/l were found in 28.4 % of the children and 2.4 % had concentrations <25 nmol/l. Upon multivariate adjustment, increasing age (per year) (beta -2.9; 95 % CI -5.1, -0.7 nmol/l), female sex (beta -3.3; 95 % CI -5.9, -0.7 nmol/l), sampling in October (beta -5.2; 95 % CI -10.1, -0.4 nmol/l) and November (beta -13.3; 95 % CI -17.7, -9.1), and non-white ethnicity (beta 5.7; 95 % CI -11.1, -0.3 nmol/l) were negatively associated with 25(OH)D (all P<0.05). Likewise, immigrant/descendant background was negatively associated with 25(OH)D, particularly in females (beta -16.3; 95 % CI -21.9, -10.7) (P<0.001) (P interaction=0.003). Moderate-to-vigorous physical activity (MVPA) (min/d) (beta 0.06; 95 % CI 0.01, 0.12), outdoor walking during school hours (min/week) (beta 0.4; 95 % CI 0.1, 0.6) and intake of vitamin D-containing supplements >=3 d/week (beta 8.7; 95 % CI 6.4, 11.0) were positively associated with 25(OH)D (all P<0.05). The high proportion of children with vitamin D status below the recommended sufficiency level of 50 nmol/l raises concern as levels expectedly drop further during winter months. Frequent intake of vitamin D supplements was strongly associated with status. MVPA and outdoor activity during school hours should be investigated further in interventions to improve autumn vitamin D status in children at northern latitudes. PMID- 26563916 TI - Optimization of ultrasound-assisted extraction of bioactive compounds from wild garlic (Allium ursinum L.). AB - Ultrasound-assisted extraction was used for extraction of bioactive compounds and for production of Allium ursinum liquid extract. The experiments were carried out according to tree level, four variables, face-centered cubic experimental design (FDC) combined with response surface methodology (RSM). Temperature (from 40 to 80 degrees C), ethanol concentration (from 30% to 70%), extraction time (from 40 to 80 min) and ultrasonic power (from 19.2 to 38.4 W/L) were investigated as independent variables in order to obtain the optimal conditions for extraction and to maximize the yield of total phenols (TP), flavonoids (TF) and antioxidant activity of obtained extracts. Experimental results were fitted to the second order polynomial model where multiple regression and analysis of variance were used to determine the fitness of the model and optimal condition for investigated responses. The predicted values of the TP (1.60 g GAE/100 g DW), TF (0.35 g CE/100 g DW), antioxidant activity, IC50 (0.71 mg/ml) and EY (38.1%) were determined at the optimal conditions for ultrasound assisted extraction: 80 degrees C temperature, 70% ethanol, 79.8 min and 20.06 W/L ultrasonic power. The predicted results matched well with the experimental results obtained using optimal extraction conditions which validated the RSM model with a good correlation. PMID- 26563917 TI - Nonadiabatic Dynamics in Atomistic Environments: Harnessing Quantum-Classical Theory with Generalized Quantum Master Equations. AB - The development of methods that can efficiently and accurately treat nonadiabatic dynamics in quantum systems coupled to arbitrary atomistic environments remains a significant challenge in problems ranging from exciton transport in photovoltaic materials to electron and proton transfer in catalysis. Here we show that our recently introduced MF-GQME approach, which combines Ehrenfest mean field theory with the generalized quantum master equation framework, is able to yield quantitative accuracy over a wide range of charge-transfer regimes in fully atomistic environments. This is accompanied by computational speed-ups of up to 3 orders of magnitude over a direct application of Ehrenfest theory. This development offers the opportunity to efficiently investigate the atomistic details of nonadiabatic quantum relaxation processes in regimes where obtaining accurate results has previously been elusive. PMID- 26563918 TI - GaN and GaxIn1-xN Nanoparticles with Tunable Indium Content: Synthesis and Characterization. AB - Semiconducting GaN and GaxIn1-xN nanoparticles (4-10 nm in diameter, depending on the metal ratio) with tunable indium content are prepared through a chemical synthesis (the urea-glass route). The bandgap of the ternary system depends on its composition, and therefore, the color of the final material can be turned from bright yellow (the color of pure GaN) to blue (the color of pure InN). Transmission electron microscopy (TEM and HRTEM) and scanning electron microscopy (SEM) images confirm the nanoparticle character and homogeneity of the as prepared samples. X-ray diffraction (XRD), electron diffraction (EDX), elemental mapping, and UV/Vis, IR, and Raman spectroscopy investigations are used to confirm the incorporation of indium into the crystal structure of GaN. These nanoparticles, possessing adjusted optical properties, are expected to have potential applications in the fabrication of novel optoelectronic devices. PMID- 26563919 TI - Exploring the factors that influence medication rating Web sites value to older adults: A cross-sectional study. AB - In this cross-sectional study, we evaluated factors that affected the perceived value of medication rating Web sites to 284 people aged >= 60 years who were taking prescription medications. The Patient Reviews of Medication Experience (PROMEX) questionnaire score, which assessed participant opinions about the value of online reviews of medications, was positively associated with preference to share health care decision making with the health care provider and negatively associated with the Physical Component Summary (PCS-12) and Mental Component Summary scores of the Short Form 12 health survey. The Primary Care Assessment Survey Communication score, which measured participant satisfaction with the communication from the health care provider, was positively associated with PCS 12 and health literacy. In summary, older adults who had poor physical and mental health-related quality of life were more likely to believe that medication rating Web sites were useful and helpful in facilitating communication with health care providers. PMID- 26563920 TI - Surgical excision margins in primary cutaneous melanoma: A meta-analysis and Bayesian probability evaluation. AB - BACKGROUND: Surgery is the only curative treatment for primary cutaneous melanoma, therefore it is important to determine excision margins that minimise risk of local recurrence, distant recurrence and death. METHODS: MEDLINE, EMBASE and Cochrane CENTRAL were searched from 2009 to 2015. Inclusion criteria were: population/setting - patients with primary melanoma; comparison - narrow versus wide margins; outcomes - overall survival, melanoma-specific survival, recurrence free survival, and loco-regional recurrence; design - randomized controlled trials (RCTs). Results were pooled using meta-analysis and data explored using likelihood Bayesian probability plots. RESULTS: Six RCTs with 4233 patients were included. Narrow margins were defined as 1 or 2 cm of clinically normal skin around the melanoma; wide margins as 3, 4 or 5 cm. Hazard ratios (HR) were as follows (HR>1 indicates wide margin better): overall survival 1.09 (95% CI 0.98 1.22; p=0.1); melanoma-specific survival 1.17 (CI 1.03-1.34; p=0.02); recurrence free survival 1.08 (CI 0.97-1.20; p=0.2); loco-regional recurrence 1.10 (CI 0.96 1.26; p=0.2), with no evidence of heterogeneity between trials for any end point or within subgroup analyses. There was an 94% probability that overall survival was worse with a narrow margin and a 43% probability that it was more than 10% worse in proportional terms (i.e. HR>1.1). Probabilities that narrow margins were worse were 99%, 92% and 92% for melanoma-specific survival, recurrence-free survival and loco-regional recurrence respectively. CONCLUSIONS: Contrary to recommendations in several national guidelines that narrow margins are safe, this systematic review and meta-analysis provides evidence that a narrow margin may lead to a worse outcome than a wide margin. PMID- 26563921 TI - The Time-Varying Relationship between Mortality and Business Cycles in the USA. AB - We examine the relationship between total mortality, deaths due to motor vehicle accidents, cardiovascular disease and measures of business cycles for the USA, using a time-varying parameter model for the periods 1961-2010. We first present a theoretical model to outline the transmission mechanism from business cycles to health status, to motivate our empirical framework and to explain why the relationship between mortality and the economy may have changed over time. We find overwhelming evidence of structural breaks in the relationship between mortality and business cycles over the sample period. Overall, the relationship between total mortality, cardiovascular mortality and the economy has become less procyclical over time and even countercyclical in recent times for certain age groups. Deaths due to motor vehicle accidents have remained strongly procyclical. Using drugs and medical patent data and data on hours worked, we argue that important advances in medical technology and changes in the effects that working hours have on health are important reasons for this time-varying relationship. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26563922 TI - High catalytic activity and pollutants resistivity using Fe-AAPyr cathode catalyst for microbial fuel cell application. AB - For the first time, a new generation of innovative non-platinum group metal catalysts based on iron and aminoantipyrine as precursor (Fe-AAPyr) has been utilized in a membraneless single-chamber microbial fuel cell (SCMFC) running on wastewater. Fe-AAPyr was used as an oxygen reduction catalyst in a passive gas diffusion cathode and implemented in SCMFC design. This catalyst demonstrated better performance than platinum (Pt) during screening in "clean" conditions (PBS), and no degradation in performance during the operation in wastewater. The maximum power density generated by the SCMFC with Fe-AAPyr was 167 +/- 6 MUW cm( 2) and remained stable over 16 days, while SCMFC with Pt decreased to 113 +/- 4 MUW cm(-2) by day 13, achieving similar values of an activated carbon based cathode. The presence of S(2-) and showed insignificant decrease of ORR activity for the Fe-AAPyr. The reported results clearly demonstrate that Fe-AAPyr can be utilized in MFCs under the harsh conditions of wastewater. PMID- 26563923 TI - Efficacy of multimodal analgesia injection combined with corticosteroids after arthroscopic rotator cuff repair. AB - INTRODUCTION: Although arthroscopic rotator cuff repair is minimally invasive, there is still considerable postoperative pain, especially during the first 48 hours. The present study assessed the short-term efficacy and safety of multimodal analgesic (MMA) injection associated to corticosteroids in arthroscopic rotator cuff tear surgery. MATERIAL AND METHOD: A single-center prospective randomized study included 50 patients undergoing arthroscopic rotator cuff tear surgery. The study group received subacromial injection of a mixture of morphine, ropivacaine and methylprednisolone associated to intra-articular injection of morphine plus methylprednisolone; the control group received only isotonic saline. All patients had had 24 hours self-administered morphine associated to standard analgesia. Postoperative data were recorded at 30 minutes and 1, 2, 4, 6, 12, 18 and 24 hours: pain intensity, morphine intake and side effects, and also time to first morphine bolus and additional analgesic intake. Constant, ASES and SST functional scores were recorded at 3 months. RESULTS: Postoperative pain was significantly less intense in the MMA group than in controls at 30 min, H1, H4, H6, H12, H18 and H24 (P<0.05). A rebound at D10 occurred in both groups. During the first 24 hours, MMA significantly reduced cumulative resort to morphine (P<0.05 at H1/2, P<0.001 at H1-24). Mean time to first bolus was significantly longer in the MMA group (71.6 vs. 33 min; P<0.05). The rate of opioid-related side effects was similar between groups. At last follow-up, functional scores were similar between groups. There were no cases of infection or delayed skin healing. CONCLUSION: MMA associated to corticosteroids after arthroscopic rotator cuff tear surgery provided immediate benefit in terms of analgesia and morphine sparing, without apparent risk of infection. The practice is presently little known in France and deserves longer-term assessment, especially as regards functional rehabilitation and tendon healing. LEVEL OF EVIDENCE: 2. PMID- 26563924 TI - Ten-year follow-up of acute arthroscopic Bankart repair for initial anterior shoulder dislocation in young patients. AB - INTRODUCTION: Early treatment of initial anterior glenohumeral dislocation in young patients is controversial and the interest of surgery, and notably arthroscopic stabilization, has not been demonstrated. A prospective study was therefore performed to assess (1) short-to-medium-term recurrence rate, (2) functional outcome, and (3) and medium-term osteoarthritis rate. HYPOTHESIS: Early arthroscopic stabilization by anterior capsule-labrum reinsertion after initial anterior shoulder dislocation is associated with low recurrence rate. MATERIALS AND METHODS: Twenty-one patients with initial anterior dislocation were included between June 2002 and February 2004. All patients underwent arthroscopic Bankart repair within 30 days of dislocation. Patients were followed up prospectively, with clinical (Duplay and Constant scores) and radiological assessment (osteoarthritis). RESULTS: There were 5 recurrent dislocations (25%); 2 patients reported sensations of subluxation: i.e., 7 failures (35%). Mean Walch Duplay score at 10 years was 88+/-1 (range, 30-100) and mean Rowe score 86+/-22 (range, 35-100). There was significant internal rotation deficit of one vertebral level between operated and contralateral shoulder (P < 0.005). At 10 years, 3 shoulders (15%) showed Samilson grade 1 centered glenohumeral osteoarthritis. CONCLUSION: Early arthroscopic capsule-labrum reinsertion by the Bankart technique in the month following initial anterior dislocation of the shoulder in patients under 25 years of age provided a low recurrence rate (35%) compared to the literature, including dislocation (25%) and subluxation (10%). Functional outcome was satisfactory, and osteoarthritis rate was low (15% Samilson grade 1). LEVEL OF EVIDENCE: IV, prospective non-comparative study. PMID- 26563925 TI - Reviewers needed: apply here. AB - Peer review is an essential task in the professional publishing process. Reviewers provide a vital service to journals and their expert reviews guide the editor when making decisions about what will and will not be published. PMID- 26563926 TI - Conceptual frameworks and terminology in doctoral nursing research. AB - AIM: To define conceptual frameworks and their inherent dichotomies, and integrate them with concomitant concepts to help early nursing doctoral researchers to develop their understanding of and engage with discourse further, so that nursing can demonstrate its ability to contribute to the meta-theoretical debate of doctoral research alongside other practices and theory-based disciplines. BACKGROUND: Conceptual frameworks are central to nursing doctoral studies as they map and contextualise the philosophical assumptions of the research in relation to paradigms and ontological, epistemological and methodological foundations. They shape all aspects of the research design and provide a structure for theorising. They can also be a challenge for researchers and are under-discussed in the literature. REVIEW METHODS: Literature review. DISCUSSION: The key aspects of the conceptual framework debate in terms of objectivist, subjectivist paradigms and the wider paradigm debate, including retroduction and abduction, are reviewed here together with consideration of how these apply to nursing doctoral research. CONCLUSION: Conceptual frameworks are pivotal to nursing doctoral research as they clarify and integrate philosophical, methodological and pragmatic aspects of doctoral thesis while helping the profession to be seen as a research-based discipline, comfortable with the language of meta-theoretical debate. IMPLICATIONS FOR RESEARCH/PRACTICE: Conceptual frameworks should form the methodological foundation for all nursing doctoral research. PMID- 26563927 TI - Ethnonursing and the ethnographic approach in nursing. AB - AIM: To present a critical methodological review of the ethnonursing research method. BACKGROUND: Ethnonursing was developed to underpin the study and practice of transcultural nursing and to promote 'culturally congruent' care. Ethnonursing claims to produce accurate knowledge about cultural groups to guide nursing care. The idea that the nurse researcher can objectively and transparently represent culture still permeates the ethnonursing method and shapes attempts to advance nursing knowledge and improve patient care through transcultural nursing. DATA SOURCES: Relevant literature published between the 19th and 21st centuries. REVIEW METHODS: Literature review. DISCUSSION: Ethnography saw a 'golden age' in the first half of the 20th century, but the foundations of traditional ethnographic knowledge are being increasingly questioned today. CONCLUSION: The authors argue that ethnonursing has failed to respond to contemporary issues relevant to ethnographic knowledge and that there is a need to refresh the method. This will allow nurse researchers to move beyond hitherto unproblematic notions of objectivity to recognise the intrinsic relationship between the nurse researcher and the researched. IMPLICATIONS FOR RESEARCH/PRACTICE: A revised ethnonursing research method would enable nurse researchers to create reflexive interpretations of culture that identify and embody their cultural assumptions and prejudices. PMID- 26563928 TI - Influence of communal and private folklore on bringing meaning to the experience of persistent pain. AB - AIM: To provide an overview of the relevance and strengths of using the literary folkloristic methodology to explore the ways in which people with persistent pain relate to and make sense of their experiences through narrative accounts. BACKGROUND: Storytelling is a conversation with a purpose. The reciprocal bond between researcher and storyteller enables the examination of the meaning of experiences. Life narratives, in the context of wider traditional and communal folklore, can be analysed to discover how people make sense of their circumstances. DATA SOURCES: This paper draws from the experience of the author, who has previously used this narrative approach. It is a reflection of how the approach may be used to understand those experiencing persistent pain without a consensual diagnosis. REVIEW METHODS: Using an integrative method, peer-reviewed research and discussion papers published between January 1990 and December 2014 and listed in the CINAHL, Science Direct, PsycINFO and Google Scholar databases were reviewed. In addition, texts that addressed research methodologies such as literary folkloristic methodology and Marxist literary theory were used. DISCUSSION: The unique role that nurses play in managing pain is couched in the historical and cultural context of nursing. Literary folkloristic methodology offers an opportunity to gain a better understanding and appreciation of how the experience of pain is constructed and to connect with sufferers. CONCLUSION: Literary folkloristic methodology reveals that those with persistent pain are often rendered powerless to live their lives. Increasing awareness of how this experience is constructed and maintained also allows an understanding of societal influences on nursing practice. IMPLICATIONS FOR PRACTICE/RESEARCH: Nurse researchers try to understand experiences in light of specific situations. Literary folkloristic methodology can enable them to understand the inter relationship between people in persistent pain and how they construct their experiences. PMID- 26563929 TI - Selecting a measure for assessing secondary trauma in nurses. AB - AIM: To summarise the usefulness of available psychometric tools in assessing secondary trauma in nursing staff and examine their limitations, as well as their strengths, to enable researchers to select the most suitable measures. BACKGROUND: Secondary trauma is an extreme persistent reaction that can be experienced by nursing staff following exposure to a potentially life-threatening situation. This relatively new concept is increasingly used to explore staff distress, but is complicated by various definitions. In this growing and popular field, few rigorously tested measures are used. Therefore, it is timely to examine the measures available and their robustness. DATA SOURCES: In March 2014 the following databases were used: BNI, CINAHL, EMBASE, PILOTS, Medline, PsycINFO and the Cochrane Library. REVIEW METHODS: A systematic search of nurse and health research databases was conducted from 1980 to 2014 using the terms nurs* AND PTSD OR Posttraumatic Stress Disorder OR secondary trauma OR secondary traumatic stress OR STS OR compassion fatigue. DISCUSSION: To strengthen confidence in research findings and make the most useful contribution to practice, researchers should use the most rigorous measures available. Of the assessment tools used, the only one subject to robust peer review is the Secondary Traumatic Stress Scale (STSS). The scale most frequently used to assess secondary traumatic stress is the Professional Quality of Life Scale (ProQOL); its lack of psychometric evaluation is a potential weakness. CONCLUSION The STSS is the only validated tool reported in the peer-reviewed, published literature and the authors suggest greater application when secondary trauma is a suspected consequence of nursing work. Validated tools such as the HADS and GHQ-28 are more useful in assessing broader-based psychological morbidity. IMPLICATIONS FOR RESEARCH/PRACTICE: The authors suggest greater application of the STSS when secondary trauma is a suspected consequence of nursing work. Researchers interested in assessing more than trauma responses are advised to use HADS and GHQ-28. PMID- 26563930 TI - Advice for running a successful research team. AB - AIM: To explore what is meant by a 'research team' and offer practical suggestions for supporting an effective and productive, collaborative research team. BACKGROUND: Collaborative research has become one of the main objectives of most higher education institutions and running effective research teams is central to achieving this aim. However, there is limited guidance in the literature about how to run or steer a research team. DATA SOURCES: Search engines/databases used: CINAHL, Nursing and Allied Health Source, Primo search, Google search and Health Collection to access research articles and publications to support this topic. Literature search was extended to the end of 2014. REVIEW METHODS: Publications were reviewed for relevance to the topic via standard literature search. DISCUSSION: Research teams vary in size and composition, however they all require effective collaboration if they are to establish successful and flexible working relationships and produce useful and trustworthy research outputs. This article offers guidance for establishing and managing successful collaborative research relationships, building trust and a positive research team culture, clarifying team member roles, setting the teams' research agenda and managing the teams' functions so that team members feel able to contribute fully to the research goals and build a culture of support and apply 'emotional intelligence' throughout the process of building and running a successful research team. CONCLUSION: Collaboration is a central component of establishing successful research teams and enabling productive research outputs. This article offers guidance for research teams to help them to function more effectively and allow all members to contribute fully to each team's goals. IMPLICATIONS FOR PRACTICE/RESEARCH: Research teams that have established trust and a positive team culture will result in more efficient working relationships and potentially greater productivity. The advice offered reinforces the value of having research teams with diverse members from different disciplines, philosophical roots and backgrounds. Each of these members should be able to contribute skills and expertise so that the parts of the team are able to develop 'synergy' and result in more productive, positive and rewarding research experiences, as well as more effective research. PMID- 26563931 TI - An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma. AB - BACKGROUND: Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. METHODS: A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. RESULTS: Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. CONCLUSIONS: NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated. PMID- 26563932 TI - Relationship between ubiquilin-1 and BACE1 in human Alzheimer's disease and APdE9 transgenic mouse brain and cell-based models. AB - Accumulation of beta-amyloid (Abeta) and phosphorylated tau in the brain are central events underlying Alzheimer's disease (AD) pathogenesis. Abeta is generated from amyloid precursor protein (APP) by beta-site APP-cleaving enzyme 1 (BACE1) and gamma-secretase-mediated cleavages. Ubiquilin-1, a ubiquitin-like protein, genetically associates with AD and affects APP trafficking, processing and degradation. Here, we have investigated ubiquilin-1 expression in human brain in relation to AD-related neurofibrillary pathology and the effects of ubiquilin 1 overexpression on BACE1, tau, neuroinflammation, and neuronal viability in vitro in co-cultures of mouse embryonic primary cortical neurons and microglial cells under acute neuroinflammation as well as neuronal cell lines, and in vivo in the brain of APdE9 transgenic mice at the early phase of the development of Abeta pathology. Ubiquilin-1 expression was decreased in human temporal cortex in relation to the early stages of AD-related neurofibrillary pathology (Braak stages 0-II vs. III-IV). There was a trend towards a positive correlation between ubiquilin-1 and BACE1 protein levels. Consistent with this, ubiquilin-1 overexpression in the neuron-microglia co-cultures with or without the induction of neuroinflammation resulted in a significant increase in endogenously expressed BACE1 levels. Sustained ubiquilin-1 overexpression in the brain of APdE9 mice resulted in a moderate, but insignificant increase in endogenous BACE1 levels and activity, coinciding with increased levels of soluble Abeta40 and Abeta42. BACE1 levels were also significantly increased in neuronal cells co-overexpressing ubiquilin-1 and BACE1. Ubiquilin-1 overexpression led to the stabilization of BACE1 protein levels, potentially through a mechanism involving decreased degradation in the lysosomal compartment. Ubiquilin-1 overexpression did not significantly affect the neuroinflammation response, but decreased neuronal viability in the neuron-microglia co-cultures under neuroinflammation. Taken together, these results suggest that ubiquilin-1 may mechanistically participate in AD molecular pathogenesis by affecting BACE1 and thereby APP processing and Abeta accumulation. PMID- 26563933 TI - A spectrum of exercise training reduces soluble Abeta in a dose-dependent manner in a mouse model of Alzheimer's disease. AB - Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Abeta40 and Abeta42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week, from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect in these mice. Soluble Abeta40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Abeta42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Abeta clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular soluble Abeta in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Abeta clearance. PMID- 26563934 TI - The syndrome of inappropriate antidiuretic hormone secretion: Distribution and characterization according to etiologies. AB - PURPOSE: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients and to characterize patients according to the different etiologies. METHODS: A single center retrospective study including all patients diagnosed with SIADH in a large community hospital and tertiary center between 1.1.2007 and 1.1.2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 555 patients. The most common etiologies were malignancies and medication-induced SIADH, followed by idiopathic SIADH, pulmonary infections, pain and nausea, and central nervous system (CNS) disorders. Subgroup analysis according to etiology showed that CNS disorders were associated with more severe episodes of SIADH. Patients with idiopathic SIADH were older than patients with a specific diagnosis, had a lower urine osmolality, and required less treatment with hypertonic saline. Long-term survival was determined primarily by SIADH etiology rather than hyponatremia severity, with hazard ratios for death of up to 7.31 (95% CI 4.93-10.82, p<0.001) for patients with malignancy-associated SIADH as compared to patients with idiopathic SIADH. Hyponatremia grade at short-term follow-up was also predictive for long-term survival (HR 1.42 per grade, 95% CI 1.21-1.66, p<0.001). CONCLUSIONS: Patients with SIADH have different characteristics and a different prognosis according to SIADH etiology. Serum sodium concentration at short-term follow-up is predictive of long-term survival. These findings might have diagnostic and treatment-related implications. PMID- 26563935 TI - A cause for craniocervical pain. PMID- 26563936 TI - Producing evidence in support of disinvestment: The experience of the Tuscany region in Italy. PMID- 26563937 TI - Prolonged length of stay in hospitalized internal medicine patients. AB - BACKGROUND: Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). OBJECTIVE: We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. DESIGN: We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. KEY RESULTS: Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87 0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). CONCLUSIONS: Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home. PMID- 26563938 TI - TMEM16A/ANO1 is differentially expressed in HPV-negative versus HPV-positive head and neck squamous cell carcinoma through promoter methylation. AB - Head and neck squamous cell carcinoma (HNSCC) has a variety of causes. Recently, the human papilloma virus (HPV) has been implicated in the rising incidence of oropharyngeal cancer and has led to variety of studies exploring the differences between HPV-positive and HPV-negative HNSCC. The calcium-activated chloride channel TMEM16A is overexpressed in a variety of cancers, including HNSCC, but whether or not it plays different roles in HPV-positive and HPV-negative HNSCC is unknown. Here, we demonstrate that TMEM16A is preferentially overexpressed in HPV negative HNSCC and that this overexpression of TMEM16A is associated with decreased patient survival. We also show that TMEM16A expression is decreased in HPV-positive HNSCC at the DNA, RNA, and protein levels in patient samples as well as cell lines. We demonstrate that the lower levels of TMEM16A expression in HPV positive tumors can be attributed to both a combination of copy number alteration and promoter methylation at the DNA level. Additionally, our cellular data show that HPV-negative cell lines are more dependent on TMEM16A for survival than HPV positive cell lines. Therefore, we suspect that the down-regulation of TMEM16A in HPV-positive HNSCC makes TMEM16A a poor therapeutic target in HPV-positive HNSCC, but a potentially useful target in HPV-negative HNSCC. PMID- 26563939 TI - Substituted ferrocenes and iodine as synergistic thermoelectrochemical heat harvesting redox couples in ionic liquids. AB - Combining ferrocene and iodine results in enhanced thermoelectrochemical (or thermogalvanic) waste heat harvesting abilities, for both the Seebeck coefficient and the overall power output. All systems displayed a mixture of ferrocene, ferrocenium, iodine and triiodide. The observed enhancement correlates with lower electron-density on the ferrocene; the synergistic improvement observed for mixtures of substituted ferrocenes and iodine is attributed to the formation of charge-transfer complexes. Combining dibutanoylferrocene and iodine resulted in the highest Seebeck coefficient of 1.67 mV K(-1). PMID- 26563940 TI - Enhanced Periodontal Regeneration by Novel Single Application Sustained Release Nano-Structured Doxycycline Films. AB - The use of different drug classes as host modulating agents has been postulated to have significance as an adjunctive remedy curing chronic periodontitis. In this study nano-structured films containing doxycyclin (DOX) were evaluated for such purpose. Nano DOX/chitosan particulate system was prepared using spray drying technique and was then incorporated in PVA-based films. The particles were evaluated for particle size, zeta potential and possible drug/polymer interaction. The films were also tested for in-vitro drug release and clinical efficacy compared with placebo and DOX-loaded films. The formed particles had a zeta potential of + 13.8 mV and particle size of 52.86 nm with a polydispersity of PDI=0.946. No significant drug/polymer interaction was detected by DSC thermal analysis. In-vitro DOX release was sustained for about a week with the nano structured films showing 23% of the drug released compared with 44% released from DOX films. Clinical efficacy was done on 150 periodontal pockets from patients suffering from moderate chronic periodontitis. Following scaling and root planning they were divided into three groups; group I receiving nano-structured (DOX), group II receiving DOX and group III receiving placebo films. Evaluation was done both clinically and biochemically at base-line, 1 week, 1 month and 2 months following drug application. Clinical findings indicated a significant effect of both nano-structured and DOX films in improving the measured parameters compared with the control and placebo groups. PMID- 26563941 TI - Preparation, Characterization and in vivo Evaluation of Simple Monolithic Ethylcellulose-coated Pellets Containing Topiramate with Biphasic Release Characteristics. AB - In our previous study, polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former to prepare ethylcellulose (EC)-coated pellets to deliver topiramate (TPM) for a controlled release profile. The objective of this work was to further optimize the formulation and evaluate the in vivo profiles of TPM sustained release pellets. Similar to the previous formulation with no binder, the in vitro drug release of TPM sustained-release pellets with 50% PVP binder in drug layer was sensitive to pore-former PVP level ranged from 27.0% to 29.0%. The higher the level of PVP was, the quicker release rate in vitro was. Moreover, when the proportion of poreformer PVP decreased, the Cmax decreased, and the tmax and mean residence time of TPM coated pellets were both prolonged. The in vitro release profile of optimal formulation showed biphasic release characteristics similar to reference formulation Trokendi XR((r)), i.e., involving immediate release of TPM in initial release stage followed by a sustained release up to 24 h. Moreover, the impact of the pH of release medium on the drug release rate of TPM sustained release pellets was not significant. The release mechanism of TPM from the sustained-release pellets might be the interaction of diffusion (coating-film) and corrosion (drug layer). The in vivo pharmacokinetics results showed the TPM sustained-release pellets had the similar in vivo pattern compared with Trokendi XR((r)). These studies provide valuable basis for further development of TPM sustained-release pellets. PMID- 26563942 TI - Evaluation of the Therapeutic Properties of Mastoparan- and Sifuvirtide- Derivative Antimicrobial Peptides Using Chemical Structure-Function Relationship in vivo and in silico Approaches. AB - Antimicrobial peptides, also called body defense peptides, are chemical structures widely distributed across the animal and vegetal kingdoms that have a fundamental role as part of the immune system. These peptides are used against a wide range of pathogens, such as Gram-negative and - positive bacteria, fungi and viruses, etc. Their action spectrum makes them important for the pharmaceutical industry, as they could represent templates for the design of new and more potent structures by using drug design and drug delivery systems. Here we present the antimicrobial activity against Bacillus subtilis (expressed as minimal inhibitory concentration values) for 33 mastoparan analogs and their new derivatives by quantitative structure-activity relationship method (2D, aligned and also non aligned 3D-QSAR). We establish the contribution to antimicrobial activity of molecular descriptors like hydrophobicity, hydrogen bond donor and steric hindrance, correlated with contributions from the membrane environment (sodium, potassium, chloride ions). Also the studies of HIV-1 fusion inhibitor sifuvirtide and its analogs are presented in context of interaction with lipid structures during fusion and delivery of these drugs. PMID- 26563943 TI - Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization. AB - Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release. PMID- 26563944 TI - Production of Irbesartan Nanocrystals by High Shear Homogenisation and Ultra Probe Sonication for Improved Dissolution Rate. AB - Irbesartan (IRB) is a BCS class II drug with poorly aqueous solubility and its absorption is dissolution rate limited. In the present study solubility and dissolution rate of IRB were improved by nanonization and using two poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) amphiphiles, namely Pluronic(r) F127 and Pluronic(r) F68, as nanosuspension stabilisers. In addition, the role of these surfactants in the solubilization of the drug was assessed. The nanocrystals were produced by two top-down techniques- high shear homogenisation and ultra-probe sonication. The nanocrystals were characterized for particle size, size distribution and zeta potential and compared to the unprocessed drug by FTIR, thermal analysis, scanning electron microscopy, solubility and dissolution rate. IRB nanocrystals showed greater solubility and faster dissolution rate than the original drug, solubility being higher for formulations prepared with F127 than those with F68. Presence of an endothermic peak of drug in the formulation confirmed its crystalline nature, regardless of the use of two energetic methods. SEM of the nanocrystals revealed a small rod-shaped morphology and the substantial decrease of the particles size. Overall results support these nanonization techniques as a simple, cost-effective and scalable approach to improve the aqueous solubility of drugs such as IRB that are classified into Class II of the Biopharmaceutic Classification System (BCS). PMID- 26563945 TI - CRAM-A indicates IFN-gamma-associated inflammatory response in breast cancer. AB - Atypical chemokine receptors (ACKRs) function as endpoint regulators of chemokine gradients. These non-signaling receptors that are transiently expressed under inflammatory conditions have critical roles in the control or maintenance of immune responses. Alternatively, here, CCRL2 (ACKR5) expression was determined to be constitutive in breast cancer cells. Increased amount of CCRL2 was also found in breast tumor tissues with high immune infiltration. Its expression was upregulated in the presence of pro-inflammatory cytokines, IL-1beta, TNF-alpha, IL-6, and especially IFN-gamma? Moreover, an alternative transcript of CCRL2 gene, CRAM-A, was specifically expressed in a transient fashion under the influence of IFN-gamma. CRAM-A expression was also positively correlated with the presence of IFN-gamma mRNA in patient samples. CCRL2-associated chemotactic molecules, chemerin, CCL19 and CCL5, were also detected in cancer tissues and CCL5 mRNA level was correlated with that of CRAM-A and IFN-gamma. Hence, in breast cancer, CRAM-A becomes specifically upregulated under inflammatory stimuli and may serve as a potential marker of immune response. PMID- 26563946 TI - Inflammatory cytokines provide both infection-responsive and developmental signals for blood development: Lessons from the zebrafish. AB - Hematopoietic stem cells (HSCs) are rare, largely dormant, long-lived cells that are capable of establishing and regenerating all mature blood cell lineages throughout the life of the host. Given their therapeutic importance, understanding factors that regulate HSC development and influence HSC proliferation and differentiation is of great interest. Exploring HSC biology through the lens of infection has altered our traditional view of the HSC. The HSC can now be considered a component of the immune response to infection. In response to inflammatory cytokine signaling, HSCs enhance their proliferative state and contribute to the production of in-demand blood cell lineages. Similar cytokine signaling pathways also participate during embryonic HSC production. With its highly conserved hematopoietic system and experimental tractability, the zebrafish model has made significant contributions to the hematopoietic field. In particular, the zebrafish system has been ideally suited to help reveal the molecular and cellular mechanisms underlying HSC development. This review highlights recent zebrafish studies that have uncovered new mechanistic insights into how inflammatory signaling pathways influence HSC behavior during infection and HSC production within the embryo. PMID- 26563947 TI - Elicitation threshold of cobalt chloride: analysis of patch test dose-response studies. AB - BACKGROUND: Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. OBJECTIVE: To identify the dermatitis elicitation threshold levels in cobalt allergic individuals. MATERIALS AND METHODS: Published patch test dose-response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED(10)) of a population was calculated with Fieller's method. RESULTS: On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 ug cobalt/cm(2), corresponding to 30.8-259 ppm. CONCLUSIONS: Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy. PMID- 26563949 TI - The opportunities of 2D-LC in the analysis of monoclonal antibodies. PMID- 26563948 TI - Strategies for Disseminating Information on Biomedical Research on Autism to Hispanic Parents. AB - Low income Hispanic families experience multiple barriers to accessing evidence based information on Autism Spectrum Disorders (ASD). This study utilized a mixed strategy intervention to create access to information in published bio-medical research articles on ASD by distilling the content into parent-friendly English- and Spanish-language ASD Science Briefs and presenting them to participants using two socially-oriented dissemination methods. There was a main effect for short term knowledge gains associated with the Science Briefs but no effect for the dissemination method. After 5 months, participants reported utilizing the information learned and 90% wanted to read more Science Briefs. These preliminary findings highlight the potential benefits of distilling biomedical research articles on ASD into parent-friendly educational products for currently underserved Hispanic parents. PMID- 26563950 TI - Discursive constructions of youth cancer: findings from creative methods research with healthy young people. AB - PURPOSE: As part of work to understand the experiences of young people who had cancer, we were keen to examine the perspectives of peers who share their social worlds. Our study aimed to examine how cancer in young people, young people with cancer and young cancer survivors are represented through language, metaphor and performance. METHODS: We generated data using creative activities and focus group discussions with three high school drama classes and used Foucauldian discourse analysis to identify the discursive constructions of youth cancer. RESULTS: Our analysis identified two prevailing discursive constructions: youth cancer as an inevitable decline towards death and as overwhelming personhood by reducing the young person with cancer to 'cancer victim'. CONCLUSIONS: If we are to understand life after cancer treatment and how to support young people who have been treated for cancer, we need a sophisticated understanding of the social contexts they return to. Discourses shape the way young people talk and think about youth cancer; cancer as an inevitable decline towards death and as overwhelming personhood is a key discursive construction that young people draw on when a friend discloses cancer. IMPLICATIONS FOR CANCER SURVIVORS: The way cancer is constructed shapes how friends react to and relate to a young person with cancer. These constructions are likely to shape challenging social dynamics, such as bullying, that many young cancer survivors experience. Awareness of these discursive constructions can better equip young cancer survivors, their family and health professionals negotiate life after cancer. PMID- 26563951 TI - Lost workdays in uterine cervical cancer survivors compared to the general population: impact of treatment and relapse. AB - PURPOSE: The aim of the present study was to examine the risk of lost workdays due to sick leave and disability pension by treatment modality and relapse in a population-based cohort of cervical cancer survivors versus matched comparators. METHODS: We identified 1971 cervical cancer patients aged <=60 years (median 42) at diagnosis in Sweden 2003-2009 and 9254 population comparators. Information on sociodemographic and clinical characteristics, sick leave, and disability pension was retrieved from nationwide prospective registers. Differences in the annual mean number of lost workdays were calculated by linear regression, and hazard ratios (HRs) of disability pension were calculated by Cox regression analysis, with follow-up through September 2013. RESULTS: Cervical cancer patients had more lost workdays annually than comparators up to 8 years following diagnosis. Relapse-free patients had more lost workdays than comparators up to 4 years. Risk of disability pension during follow-up was increased among the relapse-free patients treated with hysterectomy (HR 1.8 [95 % confidence interval (CI) 1.1 2.8]), hysterectomy plus chemotherapy and/or radiotherapy (HR 2.5 [95 % CI 1.2 5.4]), or chemotherapy and/or radiotherapy alone (HR 3.0 [95 % CI 1.3-6.8]), compared with the population. Women treated with fertility-sparing surgery did not have more lost workdays than the population beyond the first year and were not at increased risk of disability pension. CONCLUSION: We observed a long standing increased risk of lost workdays among cervical cancer patients, overall, as well as among relapse-free patients. IMPLICATIONS FOR CANCER SURVIVORS: Extensive but not limited treatment was associated with increased risk of lost workdays, possibly reflecting an association between treatment side effects and work ability. PMID- 26563952 TI - In vitro evaluation of anticancer and antibacterial activities of cobalt oxide nanoparticles. AB - Cobalt oxide nanoparticles (Co3O4-NPs) were synthesized using simple urea-based thermal decomposition method. Phase purity and particle size of as-synthesized nanoparticles were characterized through X-ray diffraction pattern (XRD) and transmission electron microscopy. Through XRD morphology of the Co3O4-NPs was found to be variable in size with range of 36 nm. In our present study, we explored the potential cytotoxic and antibacterial effects of Co3O4-NPs in human colorectal types of cancerous cells (HT29 and SW620) and also nine Gram-positive and Gram-negative bacteria. Co3O4-NPs showed promising anticancer activity against HT29 and SW620 cells with IC50 value of 2.26 and 394.5 MUg/mL, respectively. However, no significant effect of Co3O4-NPs was observed against bacterial strains. Furthermore, a detailed study has been carried out to investigate the possible mechanism of cell death in HT29 cancer cell line through the analysis of expression level of anti-apoptotic Bcl2 and BclxL markers. Western blot analysis results suggested significant role of Co3O4-NPs exposure in cell death due to apoptosis. PMID- 26563953 TI - Effect of low-level phototherapy on delayed onset muscle soreness: a systematic review and meta-analysis. AB - To determine the effectiveness of low-level phototherapy (i.e. light-emitting diode therapy [LEDtherapy] or light amplification by stimulated emission of radiation therapy [LASERtherapy]) on pain, skeletal muscle injury (creatine kinase [CK] levels and edema) and skeletal muscle function (range of movement and strength) in people undergoing an exercise protocol. (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PEDro, SciELO and LILACS up to May 2014), we included randomized controlled trials, quasi-randomized controlled trials and crossover studies in which study participants were allocated to receive either low-level phototherapy or placebo treatment. Phototherapy should have been applied in a single treatment session, either before or after an exercise protocol. We identified 15 studies involving 317 participants. Meta-analyses were limited by substantial heterogeneity. Compared to the placebo group, reduction in CK levels was only observed when LASERtherapy was applied before an exercise protocol (standardized mean difference = -0.66; 95 % CI = -1.30, -0.02). No between-group difference in edema, range of movement and strength were detected when phototherapy was applied before or after exercise. Evidence from this review suggests that low-level phototherapy may not have substantial effect in the treatment of skeletal muscle injury and pain caused by exercise. Definitive conclusions are limited due to the small number of included studies in each meta analysis, disparities across the included studies and small sample sizes. PMID- 26563954 TI - Lasers and nevus of Ota: a comprehensive review. AB - Nevus of Ota is a benign dermal melanocytic nevus that typically affects Asian children and women. The nevus presents as unilateral blue-gray hyperpigmented macules and patches scattered along the first and second divisions of the trigeminal nerve. Individuals with nevus of Ota experience emotional and psychosocial distress related to cosmetic disfigurement and often look for treatment options. Unfortunately, even when treated early, lesions of nevus of Ota are still difficult to treat. The use of lasers for the treatment of nevus of Ota lesions has become helpful in the management of dermal nevi. Currently, Q switched (QS) lasers have been the most studied and demonstrated positive results for treatment of nevus of Ota. The purpose of this review article is to summarize the clinical efficacy and side effects associated with QS lasers and the treatment of nevus of Ota lesions. PMID- 26563955 TI - Fractional radiofrequency combined with sonophoresis to facilitate skin penetration of 5-aminolevulinic acid. AB - Ablative fractional technology has been used to improve transdermal drug delivery. However, there have been few previous in vivo investigations of the relative potency and methodology of fractional radiofrequency (RF) combined with sonophoresis. The purpose of this study was to investigate the effects of fractional RF combined with sonophoresis on 5-aminolevulinic acid (ALA) penetration of the skin. Three male domestic swine were used. The skin of the pigs was exposed to fractional RF and/or sonophoresis, followed by topical ALA application. Fluorescence intensity (FI) of porphyrin fluorescence was measured. In both the epidermis and the dermis, FI increased after fractional RF and increased additionally with the addition of sonophoresis. Fractional RF with sonophoresis effectively enhanced ALA skin penetration. Pre-fractional RF followed by posttreatment with sonophoresis can be used for ALA-photodynamic therapy to achieve higher ALA uptake. PMID- 26563956 TI - Antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: a systematic review and meta-analysis. AB - The aim of this systematic review was to investigate whether the use of antimicrobial photodynamic therapy (aPDT) as an adjuvant to scaling and root planning (SRP) yields better results than SRP alone or associated with systemic antibiotics in the treatment of aggressive periodontitis (AgP). A meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements and Cochrane Collaboration recommendations. The search for relevant studies (earliest record to January 2015) was carried out in seven databases, followed by a manual search. Methodological quality assessment of the studies selected was based on an analysis of the risk of bias. At each time point of follow-up, the existence of significant differences (p < 0.05) in clinical attachment level (CAL) gain and probing depth (PD) reduction (primary outcomes) between groups was assessed with RevMan software 5.0. Heterogeneity between studies was assessed by the Higgin test (I (2)). Four randomized controlled trials (RCTs) satisfied the eligibility criteria of this review. Only one study was found to have a low risk of bias. There were no significant differences in PD reduction (mean difference 0.33, 95 % confidence interval -0.32 to 0.98, p = 0.32) and CAL gain (mean difference 0.20, 95 % confidence interval -0.41 to 0.81, p = 0.53) between the test and control interventions. At present, therefore, when compared to SRP alone or associated with systemic antibiotics, the evidence suggests that the association of aPDT + SRP is of no additional benefit in the nonsurgical treatment of AgP. PMID- 26563957 TI - Laser treatment of congenital melanocytic nevi: a review of the literature. AB - Congenital melanocytic nevi (CMN) are nevi that are present from birth and occur in approximately 1 % of newborns. CMN may be cosmetically disfiguring and are at risk for malignant transformation. For these two reasons, CMN are frequently treated. A variety of treatment modalities have been utilized with variable efficacy, including excision, dermabrasion, curettage, chemical peels, radiation therapy, cryotherapy, electrosurgery, and lasers. The current treatment of choice for CMN is surgical excision. However, some CMN occur in cosmetically sensitive areas, where a surgical scar is less acceptable, or in inoperable locations. For these reasons, there has been increasing interest in the potential for laser treatment of CMN. The lasers that have been studied to date for the treatment of CMN include pigment-specific lasers, including ruby (694 nm), alexandrite (755 nm), and Nd:yttrium aluminum garnet (YAG) (1064 nm), as well as ablative laser treatment with CO2 laser (10,600 nm) and Er:YAG (2940 nm). To date, ruby lasers have been studied most extensively in the treatment of CMN. Ruby laser has been shown to improve the cosmetic appearance of some CMN and may be cautiously considered for lesions located in cosmetically sensitive areas that are less amenable to surgical excision. For very large CMN, ruby laser has been tried as an alternative to extensive surgical and grafting procedures. Dual treatment with Q-switched ruby laser and normal mode ruby laser may provide the best outcomes; however, multiple treatment sessions should be anticipated. The practicality and expense of multiple treatments should be discussed with the patient prior to initiating treatment. Importantly, because of the persistence of dermal nevus cells, lifelong follow-up is required for all laser-treated CMN, even those with excellent cosmetic effect. PMID- 26563958 TI - Helping medical students to acquire a deeper understanding of truth-telling. AB - PROBLEM: Truth-telling is an important component of respect for patients' self determination, but in the context of breaking bad news, it is also a distressing and difficult task. INTERVENTION: We investigated the long-term influence of a simulated patient-based teaching intervention, integrating learning objectives in communication skills and ethics into students' attitudes and concerns regarding truth-telling. We followed two cohorts of medical students from the preclinical third year to their clinical rotations (fifth year). Open-ended responses were analysed to explore medical students' reported difficulties in breaking bad news. CONTEXT: This intervention was implemented during the last preclinical year of a problem-based medical curriculum, in collaboration between the doctor-patient communication and ethics programs. OUTCOME: Over time, concerns such as empathy and truthfulness shifted from a personal to a relational focus. Whereas 'truthfulness' was a concern for the content of the message, 'truth-telling' included concerns on how information was communicated and how realistically it was received. Truth-telling required empathy, adaptation to the patient, and appropriate management of emotions, both for the patient's welfare and for a realistic understanding of the situation. LESSONS LEARNED: Our study confirms that an intervention confronting students with a realistic situation succeeds in making them more aware of the real issues of truth-telling. Medical students deepened their reflection over time, acquiring a deeper understanding of the relational dimension of values such as truth-telling, and honing their view of empathy. PMID- 26563959 TI - Student perceptions of reproductive health education in US medical schools: a qualitative analysis of students taking family planning electives. AB - BACKGROUND: Abortion services will be sought by an estimated one in three US women before they reach age 45. Despite the importance of family planning (FP) care, many medical schools do not currently offer formal education in this area, and students are unable to meet associated competency standards prior to graduation. PURPOSE: The purpose of this study was to explore students' motivations in pursuing FP electives throughout the United States, their experiences during these courses, and any impact of these rotations on their plans for future practice. METHOD: We conducted a qualitative study consisting of semi-structured interviews with medical students upon completing fourth-year FP electives at US medical schools. Thirty-seven LCME-accredited US medical schools offered fourth-year FP electives. Course directors at 21 of these institutions recruited study participants between June 2012 and June 2013. Interviews were transcribed, coded, and analyzed with ATLAS/ti software to identify salient themes. RESULTS: We interviewed 29 students representing 14 institutions from all regions of the United States (East Coast, Midwest, South, and West Coast). Five central themes emerged. Medical students are using FP electives to fill gaps in the standard curriculum. Elective participation did not change students' pre elective stance on abortion. Many students intend to provide abortion in the future but identified possible limiting factors. Proficiency in contraception and options counseling were top competencies desired and gained. Students reported excellent satisfaction with FP electives and would recommend it to their peers, regardless of their personal beliefs. CONCLUSIONS: Interview data revealed that students are using FP electives to fill gaps within preclinical and clinical medical school curriculum. Future physicians will be unable to provide comprehensive care for their female patients if they are not provided with this education. Research should be directed at development and analysis of comprehensive FP curricula, which will allow students to obtain the knowledge necessary to best care for their patients. PMID- 26563960 TI - Cleveland Clinic's summer research program in reproductive medicine: an inside look at the class of 2014. AB - BACKGROUND: The American Center for Reproductive Medicine's summer internship course in reproductive medicine and research at Cleveland Clinic is a rigorous, results-oriented annual program that began in 2008 to train both local and international students in the fundamentals of scientific research and writing. The foremost goal of the program is to encourage premedical and medical students to aspire toward a career as a physician-scientist. The internship provides participants with an opportunity to engage in original bench research and scientific writing while developing theoretical knowledge and soft skills. This study describes selected survey responses from interns who participated in the 2014 internship program. The objective of these surveys was to elicit the interns' perspective on the internship program, its strengths and weaknesses, and to obtain insight into potential areas for improvement. METHODS: Questionnaires were structured around the five fundamental aspects of the program: 1) theoretical knowledge, 2) bench research, 3) scientific writing, 4) mentorship, and 5) soft skills. In addition, an exit survey gathered information on factors that attracted the interns to the program, communication with mentors, and overall impression of the research program. RESULTS: The opportunity to experience hands-on bench research and scientific writing, personalized mentorship, and the reputation of the institution were appreciated and ranked highly among the interns. Nearly 90% of the interns responded that the program was beneficial and well worth the time and effort invested by both interns and faculty. CONCLUSION: The outcomes portrayed in this study will be useful in the implementation of new programs or refinement of existing medical research training programs. PMID- 26563961 TI - Intrathecal baclofen for treating spasticity in children with cerebral palsy. AB - BACKGROUND: Cerebral palsy is a disorder of movement and posture arising from a non-progressive lesion in the developing brain. Spasticity, a disorder of increased muscle tone, is the most common motor difficulty and is associated with activity limitation to varying degrees in mobility and self care.Oral baclofen, a gamma-aminobutyric acid (GABA) agonist, has been used in oral form to treat spasticity for some time, but it has a variable effect on spasticity and the dose is limited by the unwanted effect of excessive sedation. Intrathecal baclofen produces higher local concentrations in cerebrospinal fluid at a fraction of the equivalent oral dose and avoids this excessive sedation. OBJECTIVES: To determine whether intrathecal baclofen is an effective treatment for spasticity in children with cerebral palsy. SEARCH METHODS: We searched the CENTRAL, MEDLINE, EMBASE and CINAHL databases, handsearched recent conference proceedings, and communicated with researchers in the field and pharmaceutical and drug delivery system companies. SELECTION CRITERIA: We included studies which compared the effect of intrathecal baclofen treatment on spasticity, gross motor function or other areas of function with controls. DATA COLLECTION AND ANALYSIS: Two authors selected studies, two authors extracted data and two authors assessed the methodological quality of included studies. MAIN RESULTS: Six studies met the inclusion criteria. The data obtained were unsuitable for the conduct of a meta-analysis; we have completed a qualitative summary.All studies were found to have high or unclear risk of bias in some aspects of their methodology.Five of the six studies reported data collected in the randomised controlled phase of the study. A sixth study did not report sufficient results to determine the effect of intrathecal baclofen versus placebo. Of these five studies, four were conducted using lumbar puncture or other short-term means of delivering intrathecal baclofen. One study assessed the effectiveness of implantable intrathecal baclofen pumps over six months.The four short-term studies demonstrated that intrathecal baclofen therapy reduces spasticity in children with cerebral palsy. However, two of these studies utilised inappropriate techniques for statistical analysis of results. The single longer-term study demonstrated minimal reduction in spasticity with the use of intrathecal baclofen therapy.One of the short-term studies and the longer term study showed improvement in comfort and ease of care. The longer term study found a small improvement in gross motor function and also in some domains of health related quality of life.Some caution is required in interpreting the findings of the all the studies in the review due to methodological issues. In particular, there was a high risk of bias in the methodology of the longer term study due to the lack of placebo use in the control group and the absence of blinding to the intervention after randomisation for both participants and investigators. AUTHORS' CONCLUSIONS: There is some limited short-term evidence that intrathecal baclofen is an effective therapy for reducing spasticity in children with cerebral palsy. The effect of intrathecal baclofen on long-term spasticity outcomes is less certain.The validity of the evidence for the effectiveness of intrathecal baclofen in treating spasticity in children with cerebral palsy from the studies in the review is constrained by the small sample sizes of the studies and methodological issues in some studies.Spasticity is a impairment in the domain of body structure and function. Consideration must also be given to the broader context in determining whether intrathecal baclofen therapy is effective. The aim of therapy may be, for example, to improve gross motor function, to increase participation at a social role level, to improve comfort, to improve the ease of care by others or to improve the overall quality of life of the individual. Intrathecal baclofen may improve gross motor function in children with cerebral palsy, but more reliable evidence is needed to determine this.There is some evidence that intrathecal baclofen improves ease of care and the comfort and quality of life of the individuals receiving it, but again small sample sizes and methodological issues in the studies mean that these results should be interpreted with caution.Further evidence of the effectiveness of intrathecal baclofen for treating spasticity, increasing gross motor function and improving comfort, ease of care and quality of life is needed from other investigators in order to validate these results.The short duration of the controlled studies included in this review did not allow for the exploration of questions regarding whether the subsequent need for orthopaedic surgery in children receiving intrathecal baclofen therapy is altered, or the safety and the economic implications of intrathecal baclofen treatment when long-term therapy is administered via an implanted device. Controlled studies are not the most appropriate study design to address these questions, cohort studies may be more appropriate. PMID- 26563962 TI - Phytotherapy for diabetes mellitus: back to nature. PMID- 26563963 TI - Effect of a simulation-based workshop on multidisplinary teamwork of newborn emergencies: an intervention study. AB - BACKGROUND: Video analyses of real-life newborn resuscitations have shown that Neonatal Resuscitation Program (NRP) guidelines are followed in fewer than 50% of cases. Multidisciplinary simulation is used as a first-rate tool for the improvement of teamwork among health professionals. In the study we evaluated the impact of the crisis resource management (CRM) and anesthesia non-technical skills instruction on teamwork during simulated newborn emergencies. METHODS: Ninety-nine participants of two delivery units (17 pediatricians, 16 anesthesiologists, 14 obstetricians, 31 midwives, and 21 neonatal nurses) were divided to an intervention group (I-group, 9 teams) and a control group (C-group, 6 teams). The I-group attended a CRM and ANTS instruction before the first scenario. After each scenario the I-group performed either self- or peer assessment depending on whether they had acted or observed in the scenario. All the teams participated in two and observed another two scenarios. All the scenarios were video-recorded and scored by three experts with Team Emergency Assessment Measure (TEAM). SPSS software and nlme package were used for the statistical analyses. RESULTS: The total TEAM scores of the first scenario between the I- and C-group did not differ from each other. Neither there was an increase in the TEAM scoring between the first and second scenario between the groups. The CRM instruction did not improve the I-group's teamwork performance. Unfortunately the teams were not comparable because the teams had been allowed to self-select their members in the study design. The total TEAM scores varied a lot between the teams. Mixed-model linear regression revealed that the background of the team leader had an impact on differences of the total teamwork scores (D = 6.50, p = 0.039). When an anesthesia consultant was the team leader the mean teamwork improved by 6.41 points in comparison to specialists of other disciplines (p = 0.043). CONCLUSION: The instruction of non-technical skills before simulation training did not enhance the acquisition of teamwork skills of the intervention groups over the corresponding set of skills of the control groups. The teams led by an anesthesiologist scored the best. Experience of team leaders improved teamwork over the CRM instruction. PMID- 26563964 TI - Reference Values for Exercise Systolic Blood Pressure in 12- to 17-Year-Old Adolescents. AB - OBJECTIVE: In adults, blood pressure (BP) during exercise has prognostic advantages compared to resting BP, whereas its relevance for children has not been revealed as clearly. Because exercise BP among young subjects might be of clinical importance, we sought to determine reference values in adolescents. METHODS: BP recordings at rest and during a cycle ergometer test (1.5W/kg) were assessed in 492 teenagers (12-17 years) in the Kiel EX.PRESS. Study (EXercise and PRESSure). The resting systolic BP (SBP) values at the 90th and 95th percentile of the German reference population were applied on our resting SBP distribution. The resulting resting SBP percentiles were then used to propose exercise SBP limits. RESULTS: Of our group, 12.4% exhibited a resting SBP >= 90th reference percentile, with 7.9% >= 95th percentile. The corresponding age group- and sex specific percentiles were assigned to the exercise SBP distribution resulting in reference values for high normal and elevated SBP (upper limit, girls/boys, mm Hg): 172/172 for 12-13 years, 174.7/177.3 for 14-15 years, 178.5/201.3 for 16-17 years). Using these limits, exercise SBP values were elevated in 8.1%, 5.5% were within the high normal range. Normal resting SBP but at least high normal exercise SBP was found in 7.7%. In contrast, 7.4% were high normal or hypertensive at rest but normotensive during exercise. CONCLUSIONS: Exercise BP is expected to be of additional use for the evaluation of BP in younger age groups. As long as prognostic data for exercise BP in adolescents are not available, the limits proposed might be considered in clinical practice. PMID- 26563966 TI - Pulmonary hypertension in patients on chronic hemodialysis and with heart failure. AB - Pulmonary hypertension (PH) is linked to chronic kidney disease. However, few studies have examined the prevalence, risk factors, or outcomes of PH in patients with chronic hemodialysis and concomitant heart failure. This retrospective cohort study enrolled 160 patients with a history of acute decompensated heart failure after maintenance hemodialysis therapy. All patients were prospectively observed until December 2013 or death. PH was defined as pulmonary artery systolic pressure >35 mmHg, as determined through echocardiography. Fifty-one (32%) patients had PH, more of whom were female (70% vs. 52%, P = 0.04). The patients with PH had a lower body mass index (21.8 vs. 23.0, P = 0.03), higher cardiothoracic ratio (55% vs. 52%, P = 0.006), larger left atrium (38.5 vs. 35.7 mm, P = 0.01), and an increased proportion of mitral regurgitation (MR) (73% vs. 38%, P < 0.001) compared with the patients who did not have PH. In the multivariate regression analysis, MR was associated most strongly with PH (odds ratio 3.75, 95% confidence interval [CI]: 1.67-8.43, P = 0.001). In the multivariate Cox proportional hazard models, PH was related independently to all cause mortality (hazard ratio [HR], 3.11; 95% CI, 1.53-6.31; P = 0.002) and combined cardiovascular events (HR, 2.71; 95% CI, 1.66-4.44; P < 0.001) after the model was adjusted for conventional cardiovascular risk factors. PH is related to MR and independently associated with increased all-cause mortality and cardiovascular events in patients with chronic hemodialysis and heart failure. PMID- 26563965 TI - Hypertension and Its Role in Cognitive Function: Current Evidence and Challenges for the Future. AB - This review summarizes evidence from studies of blood pressure and dementia related biomarkers into our understanding of cognitive health and highlights the challenges facing studies, particularly randomized trials, of hypertension and cognition. Several lines of research suggest that elevated blood pressure, especially at midlife, is associated with cognitive decline and dementia and that treatment of hypertension could prevent these conditions. Further, studies of hypertension and brain structure show that blood pressure is associated with several forms of small vessel disease that can result in vascular dementia or interact with Alzheimer's pathology to lower the pathologic threshold at which Alzheimer's signs and symptoms manifest. In addition, recent studies of hypertension and Alzheimer's biomarkers show that elevated blood pressure and pulse pressure are associated with the extent of brain beta amyloid (Abeta) deposition and altered cerebral spinal fluid profiles of Abeta and tau indicative of Alzheimer's pathology. However, in spite of strong evidence of biological mechanisms, results from randomized trials of antihypertensive therapy for the prevention of cardiovascular or cerebrovascular disease that include cognitive endpoints do not strongly support the observational evidence that treatment of hypertension should be better for cognition. We propose that future clinical trials should consider including dementia biomarkers and assess genetic and cardiometabolic risk factors that have been associated with progression of the underlying disease pathology to help bridge these gaps. PMID- 26563968 TI - Macacine Herpes Virus (B Virus). AB - B virus is endemic in macaque monkeys, which are frequently used for research studies. B virus is a risk for every employee working with macaque monkeys, their tissues or cells. Although the risk for B virus infection is low, the risk of death or permanent neurological deficit is high if an exposure is not promptly evaluated and treated. Researcher training, routine use of personal protective equipment, first aid protocols, and prompt reporting to a provider knowledgeable about B virus treatment are essential to prevent this 70% lethal infection in untreated humans. This article presents the history and pathogenesis of B virus, first aid, treatment, and prevention. PMID- 26563967 TI - Perceptions of Supervision Among Injured and Non-Injured Teens Working in the Retail or Service Industry. AB - According to the National Institute for Occupational Safety and Health (NIOSH), a teen is injured every 9 minutes at work. Workplace supervision may affect whether teens are injured on the job. Because research on workplace supervision among teens is limited, the objectives of this study were to characterize the perceptions of supervision among injured and non-injured teen workers and assess the characteristics and perceptions of supervisors that may be associated with work-related injuries. In 2011, a cross-sectional survey was conducted among high school students. Teens who worked in retail or service industries (n= 270) were included in the sample. Non-injured teens were more likely to have reported that their supervisors cared about their safety, were helpful, listened well, and ensured that teen workers understood workplace safety. Most teens (70%) did not feel comfortable talking about safety issues with their supervisors. The importance of supervision and how supervisors are perceived in the workplace may be significant in creating a safety culture that leaves a lasting impression. PMID- 26563969 TI - Follicular pancreatitis: a distinct form of chronic pancreatitis-an additional mimic of pancreatic neoplasms. AB - Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID- 26563970 TI - Quality of life in persons living with HIV in Burkina Faso: a follow-up over 12 months. AB - BACKGROUND: In Burkina Faso, very little is known about the quality of life of persons living with HIV through their routine follow- up. This study aimed to assess the quality of life of persons living with HIV, and its change over a 1 year period. METHODS: Four hundred and twenty four (424) persons living with HIV were monitored during twelve (12) months from September 2012 to September 2013 in Ouagadougou, the capital city of Burkina Faso. Three interviews were conducted in order to assess the quality of life of patients and its change over time, using the World Health Organization Quality of Life assessment brief scale in patients with Human Immunodeficiency Virus infection (WHOQOL HIV-BREF). The Friedman test was used to assess significant differences in quantitative variables at each of the three follow-up interviews. Groups at baseline, at 6 months and at 12 months were compared using Wilcoxon signed rank test for quantitative data and McNemar test for qualitative variables. Pearson Chi(2) was used when needed. Multivariable logistic regression models were fit to estimate adjusted odds ratio (OR) and 95% confidence intervals (95% CI). Trends in global quality of life score and subgroups (status related to Highly Active Anti Retroviral Treatment (HAART) using univariate repeated measures analysis of variance were assessed. A p-value less than 0.05 was considered significant. RESULTS: At baseline, quality of life scores were highest in the domain of spirituality, religion and personal beliefs (SRPB) and lowest in the environmental domain. This trend was maintained during the 12-month follow-up. The global score increased significantly from the beginning up to the twelfth month of follow-up. Over the 12 months, the baseline factors that were likely to predict an increase in the global quality of life score were: not having support from relatives for medical care (P = 0.04), being under HAART (P = 0.001), being self-perceived as healthy (P = 0.03), and having a global quality of life score under 77 (P < 0.001). CONCLUSIONS: Our findings suggest the need to promote interventions to empower people living with HIV/AIDS through income generating activities. Such activities will enhance the quality of life of persons living with HIV in Burkina Faso. This could focus mostly on treatment-naive HIV patients, lacking support from relatives and those who perceive themselves as ill. PMID- 26563971 TI - Electromagnetic Initiation and Propagation of Bipolar Radiofrequency Tissue Reactions via Invasive Non-Insulated Microneedle Electrodes. AB - Radiofrequency (RF) energy can be emitted into the skin, either non- or invasively, via a monopolar mode that utilizes an active electrode and a grounded electrode or via a bipolar mode that employs two active electrodes. In this experimental study of RF tissue reactions, bipolar RF energy was emitted in vivo to micropig skin at varying microneedle penetration depths, signal amplitudes, and conduction times. Immediately after RF treatment, skin samples exhibited RF induced coagulation columns of thermal injury, separately generated around each microneedle in the dermis. In ex vivo bovine liver tissue, the thermal coagulation columns were found to be concentrated maximally around the pointed tips of each electrode. After a RF conduction time of 2 seconds, the individual areas of thermal coagulation began to converge with neighboring RF-induced coagulation columns; the convergence of coagulation columns was found to start from the tips of neighboring electrodes. PMID- 26563972 TI - Language of plants: Where is the word? AB - Plants emit biogenic volatile organic compounds (BVOCs) causing transcriptomic, metabolomic and behavioral responses in receiver organisms. Volatiles involved in such responses are often called "plant language". Arthropods having sensitive chemoreceptors can recognize language released by plants. Insect herbivores, pollinators and natural enemies respond to composition of volatiles from plants with specialized receptors responding to different types of compounds. In contrast, the mechanism of how plants "hear" volatiles has remained obscured. In a plant-plant communication, several individually emitted compounds are known to prime defense response in receiver plants with a specific manner according to the chemical structure of each volatile compound. Further, composition and ratio of volatile compounds in the plant-released plume is important in plant-insect and plant-plant interactions mediated by plant volatiles. Studies on volatile mediated plant-plant signaling indicate that the signaling distances are rather short, usually not longer than one meter. Volatile communication from plants to insects such as pollinators could be across distances of hundreds of meters. As many of the herbivore induced VOCs have rather short atmospheric life times, we suggest that in long-distant communications with plant volatiles, reaction products in the original emitted compounds may have additional information value of the distance to emission source together with the original plant-emitted compounds. PMID- 26563973 TI - Novel treatment for early-stage nasal natural killer/T-cell lymphoma: intra maxillary arterial infusion chemotherapy with concomitant radiotherapy. AB - Nasal natural killer (NK)/T-cell lymphoma (NNKTL) displays unusual clinicopathological features, and the prognosis is very poor, even in the early stages of the disease. For early stage NNKTL, we have developed a novel chemoradiotherapy regimen incorporating arterial infusion chemotherapy, administered via the superficial temporal artery, in combination with radiotherapy. The novel arterial infusion regimen consists of ifosfamide, carboplatin, methotrexate, peplomycin, and etoposide (MPVIC-P). From 2003 to 2011, 12 patients with early stage NNKTL were treated with the MPVIC-P regimen via arterial infusion with concomitant radiotherapy (54 Gy). We have previously reported on the presence of Epstein-Barr virus (EBV) genetic DNA in NNKTL. Therefore, the effect of the treatment was evaluated by using both clinical findings and serum EBV DNA copy number. The observation period ranged from 39 months to 111 months post-treatment (median: 81 months). All 12 patients achieved and maintained complete remission and, to date, show no sign of relapse. Serum EBV DNA copy numbers decreased to below detectable levels in all 12 patients tested. Manageable mucositis was the most common grade 3-4 toxicity, and it was seen in 10 (83%) patients. However, grade 3-4 hematological toxicity was only seen in 4 (33%) patients. We conclude that our regimen of intra-maxillary arterial chemotherapy with concomitant radiotherapy is an effective treatment with minimal toxicity for early stage NNKTL. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26563974 TI - MPTTF-containing tripeptide-based organogels: receptor for 2,4,6-trinitrophenol and multiple stimuli-responsive properties. AB - A series of monopyrrolotetrathiafulvalene-tripeptide conjugates have been synthesized and investigated as new low-molecular mass organogelators. It was found that most of these compounds could immobilize low-polarity solvents readily and the gelation behaviors of these gelators showed a dependence on the amino acid residues. These organogels were thoroughly studied using various techniques including atomic force microscopy (AFM), field-emission scanning electron microscopy (FE-SEM), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, (1)H NMR spectroscopy, UV-Vis absorption spectroscopy and X-ray diffraction (XRD). The results showed that the cooperative interplay of hydrogen bonding, pi-pi stacking and SS interactions were the main driving force for the formation of the gels. Of all the organogels, the aromatic solvent gels, such as toluene gel, exhibited multiple-stimulus responsiveness towards heating, shaking, chemical redox activity and the presence of anions, thus leading to reversible sol-gel phase transitions. Most interestingly, gelation in the presence of 2,4,6-trinitrophenol (TNP) in organic solvents could be observed visually with a concomitant color change through donor-acceptor interactions. The strength of the charge-transfer interaction between gelators and TNP was proportional to the incubation time and increasing critical gelation concentration (CGC). The gels could function as efficient absorbents for potential application in removal of crystal violet and rhodamine B dyes from water. PMID- 26563975 TI - High-Performance Planar-Type Photodetector on (100) Facet of MAPbI3 Single Crystal. AB - Recently, the discovery of organometallic halide perovskites provides promising routes for fabricating optoelectronic devices with low cost and high performance. Previous experimental studies of MAPbI3 optoelectronic devices, such as photodetectors and solar cells, are normally based on polycrystalline films. In this work, a high-performance planar-type photodetector fabricated on the (100) facet of a MAPbI3 single crystal is proposed. We demonstrate that MAPbI3 photodetector based on single crystal can perform much better than that on polycrystalline-film counterpart. The low trap density of MAPbI3 single crystal accounts for the higher carrier mobility and longer carrier diffusion length, resulted in a significant performance increasement of MAPbI3 photodetector. Compared with similar planar-type photodetectors based on MAPbI3 polycrystalline film, our MAPbI3 single crystal photodetector showed excellent performance with good stability and durability, broader response spectrum to near-infrared region, about 10(2) times higher responsivity and EQE, and approximately 10(3) times faster response speed. These results may pave the way for exploiting high performance perovskites photodetectors based on single crystal. PMID- 26563976 TI - Recent trends in epidemiology, sensitization and legal requirements of selected relevant contact allergens. AB - Numerous studies have focused on emerging allergens causing contact allergy and allergic contact dermatitis in eczema populations and the general population, whereas only a few European multicenter studies systematically manage to detect prevalence rates of various contact allergies over time in eczema populations. Contact allergy is a life-time condition, which may lead to allergic contact dermatitis in individuals who do not manage to avoid exposure to the ascertained allergen in question. It is therefore of utmost importance that clinicians and dermatologists have sufficient knowledge on common allergens causing contact allergies in the general and working population. This review aimed to highlight the newest knowledge of frequent allergens of clinical importance. Literature was sought from the PubmedTM database, GoogleTM scholar and textbooks. On the basis of the literature within the last 5 years, a comprehensive review of methylisothiazolinone, chromium, cobalt, rubber accelerators and fragrance ingredients were conducted. Of each allergen we discuss in detail the temporal trend of prevalence, source of exposure, clinical manifestation of allergic contact dermatitis and legislative measurements on how to regulate the exposure. PMID- 26563977 TI - Morphology of splenocaval congenital portosystemic shunts in dogs and cats. AB - OBJECTIVE: To describe the anatomy of congenital portosystemic shunts involving the splenic vein communicating with the caudal vena cava at the level of the epiploic foramen. MATERIALS AND METHODS: A retrospective review of a consecutive series of dogs and cats managed for congenital portosystemic shunts. RESULTS: Ninety-eight dogs and eight cats met the inclusion criteria of a congenital portosystemic shunt involving the splenic vein communicating with the prehepatic caudal vena cava plus recorded intra-operative mesenteric portovenography or computed tomography angiography and gross observations at surgery. All cases (both dogs and cats) had a highly consistent shunt that involved a distended gastrosplenic vein that communicated with the caudal vena cava at the level of the epiploic foramen via an anomalous left gastric vein. CLINICAL SIGNIFICANCE: The morphology of the shunt type described appeared to be a result of an abnormal communication between the left gastric vein and the caudal vena cava and the subsequent development of preferential blood flow through an essentially normal portal venous system. The abnormal communication (shunt) was through the left gastric vein and not the splenic vein, as might have been expected. This information may help with surgical planning in cases undergoing shunt closure surgery. PMID- 26563979 TI - Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life. AB - OBJECTIVE: To evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH). DESIGN: Analysis of data extracted from a population-based prospective long-term follow up study of children detected in neonatal screening. METHODS: Data of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary. RESULTS: A total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6-8.8). CONCLUSIONS: Crisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients. PMID- 26563978 TI - GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. AB - Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. PMID- 26563980 TI - ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma. AB - Papillary craniopharyngioma (PCP) is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of PCP can now be confirmed using mutation specific immunohistochemistry and targeted genetic testing. Treatment with targeted agents is now also a possibility in select situations. We recently reported a patient with a multiply recurrent PCP in whom targeting both BRAF and MEK resulted in a dramatic therapeutic response with a marked anti-tumor immune response. This work shows that activation of the MAPK pathway is the likely principal oncogenic driver of these tumors. We will now investigate the efficacy of this approach in a multicenter phase II clinical trial. Post-treatment resection samples will be monitored for the emergence of resistance mechanisms. Further advances in the non-invasive diagnosis of PCP by radiologic criteria and by cell-free DNA testing could someday allow neo-adjuvant therapy for this disease in select patient populations. PMID- 26563981 TI - A new fluorescent dye for cell tracing and mitochondrial imaging in vitro and in vivo. AB - Mitochondria contribute to redox and calcium balance, and apoptosis thus regulating cellular fate. In the present study, mitochondrial staining applying a novel dye, V07-07059, was performed in human embryonic kidney cells, a human vascular endothelial cell line and primary human mononuclear cells. The new fluorescent mega Stokes dye (peak excitation: 488 nm, peak emission: 554 nm) showed superior fluorescent properties and stability. V07-07059 stains mitochondria dependent on their membrane potential and is safe to use in vitro and in vivo. Unlike other dyes applied in this context (e.g. Tetramethylrhodamine methyl ester), V07-07059 only marginally inhibits mitochondrial respiration and function. V07-07059 enables real time imaging of mitochondrial trafficking and remodeling. Prolonged staining with V07-07059 demonstrated the dyes suitability as a novel probe to track cells. In comparison to the widely used standard for cell proliferation and tracking studies 5(6)-diacetate N-succinimidyl ester, V07 07059 proved superior regarding toxicity and photostability. PMID- 26563982 TI - Consecutive parthenogenetic births in a spotted eagle ray Aetobatus narinari. AB - Genetic evidence is given to support consecutive parthenogenesis in a spotted eagle ray Aetobatus narinari using nuclear microsatellite genotyping. To date, only a handful of births involving the parthenogenesis process in chondrichthyans have been verified using microsatellite markers and even fewer verified as recurring births. This appears to be the first documented case of this process occurring in a myliobatid species. PMID- 26563983 TI - Gold Nanoparticle Quantitation by Whole Cell Tomography. AB - Many proposed biomedical applications for engineered gold nanoparticles require their incorporation by mammalian cells in specific numbers and locations. Here, the number of gold nanoparticles inside of individual mammalian stem cells was characterized using fast focused ion beam-scanning electron microscopy based tomography. Enhanced optical microscopy was used to provide a multiscale map of the in vitro sample, which allows cells of interest to be identified within their local environment. Cells were then serially sectioned using a gallium ion beam and imaged using a scanning electron beam. To confirm the accuracy of single cross sections, nanoparticles in similar cross sections were imaged using transmission electron microscopy and scanning helium ion microscopy. Complete tomographic series were then used to count the nanoparticles inside of each cell and measure their spatial distribution. We investigated the influence of slice thickness on counting single particles and clusters as well as nanoparticle packing within clusters. For 60 nm citrate stabilized particles, the nanoparticle cluster packing volume is 2.15 +/- 0.20 times the volume of the bare gold nanoparticles. PMID- 26563984 TI - Clinical presentation, gene analysis and outcomes in young patients with early treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China. AB - OBJECTIVES: To estimate the incidence of MMA on newborn screening in Shandong province from May 2011 to May 2014 and summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease. METHODS: Between May 2011 and May 2014, 35,291 newborns were screened for MMA in Jinan maternal and Child Care Hospital, Shandong province. The levels of C3, C3/C2, methionine and tHcy were measured. Most patients received treatment with intramuscular hydroxocobalamin after diagnosis. Metabolic parameters, clinical presentation and mental development were followed up. RESULTS: Nine patients were identified among 35,291 by newborn screening, giving an estimated incidence of 1:3920 live births for MMA, and all were classified as cblC disease. Among them, five patients received treatment with intramuscular hydroxocobalamin and two patients did not receive any treatment. One patient died of metabolic crises triggered by infection at the age of 38 days. Seven different mutations (c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A) were detected. The mutations (c.455_457delCCC and IVS1+1G>A) are novel. Five patients who received treatment had favorable metabolic response, with both reduction of urine MMA and tHcy and increase of methionine. We obtained 7 records of DQ assessment. The five patients who received treatment presented with developmental delay and obvious neurological manifestations. In two patients who did not receive any treatment, case 8 presented with severe mental retardation and developmental delay, while case 9 had nearly normal DQ values at the age of 1(1/12)years. CONCLUSION: Our study characterized variable phenotypes of neurodevelopment in early-treated cblC patients diagnosed on newborn screening. The long-term outcomes of cblC disease are unsatisfactory in spite of conventional treatment and improvement of biochemical abnormalities. Although the number of patients is too small, the information provided in this work is of value in highlighting possible genotype phenotype correlation that influences outcomes in cblC disease by future studies. PMID- 26563985 TI - Specificity of the Metalloregulator CueR for Monovalent Metal Ions: Possible Functional Role of a Coordinated Thiol? AB - Metal-ion-responsive transcriptional regulators within the MerR family effectively discriminate between mono- and divalent metal ions. Herein we address the origin of the specificity of the CueR protein for monovalent metal ions. Several spectroscopic techniques were employed to study Ag(I) , Zn(II) , and Hg(II) binding to model systems encompassing the metal-ion-binding loop of CueR from E. coli and V. cholerae. In the presence of Ag(I) , a conserved cysteine residue displays a pKa value for deprotonation of the thiol that is close to the physiological pH value. This property is only observed with the monovalent metal ion. Quantum chemically optimized structures of the CueR metal site with Cys 112 protonated demonstrate that the conserved Ser 77 backbone carbonyl oxygen atom from the other monomer of the homodimer is "pulled" towards the metal site. A common allosteric mechanism of the metalloregulatory members of the MerR family is proposed. For CueR, the mechanism relies on the protonation of Cys 112. PMID- 26563986 TI - Dietary magnesium, calcium:magnesium ratio and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma: a population-based case control study. AB - Evidence suggests a role of Mg and the ratio of Ca:Mg intakes in the prevention of colonic carcinogenesis. The association between these nutrients and oesophageal adenocarcinoma - a tumour with increasing incidence in developed countries and poor survival rates - has yet to be explored. The aim of this investigation was to explore the association between Mg intake and related nutrients and risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. This analysis included cases of oesophageal adenocarcinoma (n 218), Barrett's oesophagus (n 212), reflux oesophagitis (n 208) and population-based controls (n 252) recruited between 2002 and 2005 throughout the island of Ireland. All the subjects completed a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of disease according to dietary intakes of Mg, Ca and Ca:Mg ratio. After adjustment for potential confounders, individuals consuming the highest amounts of Mg from foods had significant reductions in the odds of reflux oesophagitis (OR 0.31; 95 % CI 0.11, 0.87) and Barrett's oesophagus (OR 0.29; 95 % CI 0.12, 0.71) compared with individuals consuming the lowest amounts of Mg. The protective effect of Mg was more apparent in the context of a low Ca:Mg intake ratio. No significant associations were observed for Mg intake and oesophageal adenocarcinoma risk (OR 0.77; 95 % CI 0.30, 1.99 comparing the highest and the lowest tertiles of consumption). In conclusion, dietary Mg intakes were inversely associated with reflux oesophagitis and Barrett's oesophagus risk in this Irish population. PMID- 26563987 TI - Head tremor in essential tremor: "Yes-yes", "no-no", or "round and round"? AB - INTRODUCTION: Essential tremor (ET) is a common yet frequently misdiagnosed movement disorder. One contributing factor may be the dearth of studies that focus on the nuances of clinical phenomenology. A clinical feature that has received relatively little attention is head tremor. Indeed, there is no consensus regarding the predominant direction of head tremor in ET, and no study has examined the clinical correlates of directionality. METHODS: We identified 51 ET cases with head tremor enrolled in a clinical-epidemiological study of ET at Columbia University. Each had a videotaped neurological examination. Videotapes were viewed and coded by a movement disorders neurologist for head tremor direction ("no-no", "yes-yes", or mixed) and continuity (continuous, intermittent, or rare). Direction was correlated with a wide range of clinical features. RESULTS: Fourteen cases (27.5%) had "no-no" tremor, 9 (17.6%) had "yes yes" tremor, and 28 (54.9%) had a mixed tremor. Mixed and "yes-yes" cases were older (p = 0.004) and had a longer tremor duration (p = 0.018) than "no-no" cases. Tremor severity (arms) was higher for mixed cases than for "yes-yes" and "no-no" cases (p = 0.04). More mixed cases had continuously present tremor while more "no-no" cases had rare head tremor (p < 0.001). CONCLUSIONS: Head tremor in ET seems to start as an infrequent tremor in one direction (esp. "no-no") and becomes more frequent while acquiring additional directionality and a mixed phenotype as the disease progresses. These findings add to our understanding of the clinical spectrum of ET. PMID- 26563988 TI - Soft Lithography Using Nectar Droplets. AB - In spite of significant advances in replication technologies, methods to produce well-defined three-dimensional structures are still at its infancy. Such a limitation would be evident if we were to produce a large array of simple and, especially, compound convex lenses, also guaranteeing that their surfaces would be molecularly smooth. Here, we report a novel method to produce such structures by cloning the 3D shape of nectar drops, found widely in nature, using conventional soft lithography.The elementary process involves transfer of a thin patch of the sugar solution coated on a glass slide onto a hydrophobic substrate on which this patch evolves into a microdroplet. Upon the absorption of water vapor, such a microdroplet grows linearly with time, and its final size can be controlled by varying its exposure time to water vapor. At any stage of the evolution of the size of the drop, its shape can be cloned onto a soft elastomer by following the well-known methods of molding and cross-linking the same. A unique new science that emerges in our attempt to understand the transfer of the sugar patch and its evolution to a spherical drop is the elucidation of the mechanics underlying the contact of a deformable sphere against a solid support intervening a thin liquid film. A unique aspect of this work is to demonstrate that higher level structures can also be generated by transferring even smaller nucleation sites on the surface of the primary lenses and then allowing them to grow by absorption of water vapor. What results at the end is either a well controlled distribution of smooth hemispherical lenses or compound structures that could have potential applications in the fundamental studies of contact mechanics, wettability, and even in optics. PMID- 26563989 TI - Coating Platinum Nanoparticles with Methyl Radicals: Effects on Properties and Catalytic Implications. AB - It was recently reported that the reaction of methyl radicals with Pt(0) nanoparticles (NPs), prepared by the reduction of Pt(SO4)2 with NaBH4, is fast and yields as the major product stable (Pt(0)-NPs)-(CH3)n and as side products, in low yields, C2H6, C2H4, and some oligomers. We decided to study the effect of this coating on the properties of the Pt(0)-NPs. The results show that the coating can cover up to 75% of the surface Pt(0) atoms. The rate constant of the reaction, k((.)CH3+Pt(0)-NPs), decreases with the increase in the surface coverage, leading to competing reaction paths in the solution, which gradually become dominant, affecting the composition of the products. The methyl coating also affects the zeta potential, the UV spectra, and the electrocatalytic reduction of water in the presence of the NPs. Thus, the results suggest that binding alkyl radicals to Pt(0) surfaces might poison the NPs catalytic activity. When the Pt(0)-NPs are prepared by the reduction of a different precursor salt, PtCl6(2-), nearly no C2 H4 and oligomers are formed and the methyl coating covers a larger percentage of the surface Pt(0) atoms. The difference is attributed to the morphology of the Pt(0)-NPs: those prepared from Pt(SO4)2 are twinned nanocrystals, whereas those prepared from PtCl6(2-) consist mostly of single crystals. Thus, the results indicate that the side products, or most of them at least, are formed on the twinned Pt(0) nanocrystal edges created between (111) facets. In addition, the results show that Pt(0)-NPs react very differently compared with other noble metals, for example, Au(0) and Ag(0); this difference is attributed in part to the difference in the bond strength, (M(0)-NP)-CH3, and should be considered in heterogeneous catalytic processes involving alkyl radicals as intermediates. PMID- 26563990 TI - Neural synchrony indexes impaired motor slowing after errors and novelty following white matter damage. AB - In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can impair the associated cognitive functions. Here, we investigated whether structural disconnection within this network because of small-vessel disease impairs the neural processes that subserve motor slowing after errors and novelty (post-error slowing, PES; post-novel slowing, PNS). Participants with intact frontostriatal circuitry showed increased right-lateralized beta-band (12-24 Hz) synchrony between frontocentral and frontolateral electrode sites in the electroencephalogram after errors and novelty, indexing increased neural communication. Importantly, this synchrony correlated with PES and PNS across participants. Furthermore, such synchrony was reduced in participants with frontostriatal white matter damage, in line with reduced PES and PNS. The results demonstrate that behavioral change after errors and novelty result from coordinated neural activity across a frontostriatal brain network and that such cognitive control is impaired by reduced white matter integrity. PMID- 26563991 TI - Assessment of the cortisol awakening response: Expert consensus guidelines. AB - The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30-45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research. PMID- 26563992 TI - Effects of Psychiatric Disorders on Labor Market Outcomes: A Latent Variable Approach Using Multiple Clinical Indicators. AB - In this paper, we estimate the effect of psychiatric disorders on labor market outcomes using a structural equation model with a latent index for mental illness, an approach that acknowledges the continuous nature of psychiatric disability. We also address the potential endogeneity of mental illness using an approach proposed by Lewbel (2012) that relies on heteroscedastic covariance restrictions rather than questionable exclusion restrictions for identification. Data come from the US National Comorbidity Survey - Replication and the National Latino and Asian American Study. We find that mental illness adversely affects employment and labor force participation and also reduces the number of weeks worked and increases work absenteeism. To assist in the interpretation of findings, we simulate the labor market outcomes of individuals meeting diagnostic criteria for mental disorder if they had the same mental health symptom profile as individuals not meeting diagnostic criteria. We estimate potential gains in employment for 3.5 million individuals, and reduction in workplace costs of absenteeism of $21.6 billion due to the resultant improvement in mental health. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26563993 TI - Large diurnal temperature range increases bird sensitivity to climate change. AB - Climate variability is changing on multiple temporal scales, and little is known of the consequences of increases in short-term variability, particularly in endotherms. Using mortality data with high temporal resolution of zebra finches living in large outdoor aviaries (5 years, 359.220 bird-days), we show that mortality rate increases almost two-fold per 1 degrees C increase in diurnal temperature range (DTR). Interestingly, the DTR effect differed between two groups with low versus high experimentally manipulated foraging costs, reflecting a typical laboratory 'easy' foraging environment and a 'hard' semi-natural environment respectively. DTR increased mortality on days with low minimum temperature in the easy foraging environment, but on days with high minimum temperature in the semi-natural environment. Thus, in a natural environment DTR effects will become increasingly important in a warming world, something not detectable in an 'easy' laboratory environment. These effects were particularly apparent at young ages. Critical time window analyses showed that the effect of DTR on mortality is delayed up to three months, while effects of minimum temperature occurred within a week. These results show that daily temperature variability can substantially impact the population viability of endothermic species. PMID- 26563994 TI - DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins. AB - Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 * 10(-8)), was significantly associated with birth weight discordance at a genome-wide false discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects. PMID- 26563995 TI - Bcl11b: A New Piece to the Complex Puzzle of Amyotrophic Lateral Sclerosis Neuropathogenesis? AB - Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, neurodegenerative disease of the human motor system. The pathogenesis of ALS is a topic of fascinating speculation and experimentation, with theories revolving around intracellular protein inclusions, mitochondrial structural issues, glutamate excitotoxicity and free radical formation. This review explores the rationale for the involvement of a novel protein, B-cell lymphoma/leukaemia 11b (Bcl11b) in ALS. Bcl11b is a multifunctional zinc finger protein transcription factor. It functions as both a transactivator and genetic suppressor, acting both directly, binding to promoter regions, and indirectly, binding to promoter-bound transcription factors. It has essential roles in the differentiation and growth of various cells in the central nervous system, immune system, integumentary system and cardiovascular system, to the extent that Bcl11b knockout mice are incompatible with extra-uterine life. It also has various roles in pathology including the suppression of latent retroviruses, thymic tumourigenesis and neurodegeneration. In particular its functions in neurodevelopment, viral latency and T-cell development suggest potential roles in ALS pathology. PMID- 26563997 TI - Emotion regulation of fear and disgust: differential effects of reappraisal and suppression. AB - Although excessive fear has been central to traditional conceptualisations of the anxiety disorders, recent research suggests that disgust may also play a role in the development of some anxiety disorders. While dysregulation of emotion may confer risk for the development of anxiety disorders, it remains unclear if there are differences in the extent to which fear and disgust can be effectively regulated. To fill this important gap in the literature, unselected participants (N = 95) experienced fear or disgust via video exposure, and they were instructed to employ either reappraisal or suppression to regulate their emotional experience while viewing the videos. For those exposed to fear-relevant content, change in emotional distress did not significantly differ between those that suppressed and those that reappraised. However, significantly less emotional distress was observed for those that reappraised compared to those that suppressed when exposed to disgust-relevant content. Although physiological arousal varied over time as a function of the emotional content of the videos, it did not vary as a function of emotion regulation strategy employed. These findings suggest that reappraisal may be especially effective in regulating verbal distress when exposed to disgusting cues in the environment. The implications of these findings for the treatment of anxiety disorders that are characterised by excessive disgust reactions will be discussed. PMID- 26563996 TI - The Crucial Involvement of Retinoid X Receptors in DDE Neurotoxicity. AB - Dichlorodiphenyldichloroethylene (DDE) is a primary environmental and metabolic degradation product of the pesticide dichlorodiphenyltrichloroethane (DDT). It is one of the most toxic compounds belonging to organochlorines. DDE has never been commercially produced; however, the parent pesticide DDT is still used in some developing countries for disease-vector control of malaria. DDT and DDE remain in the environment because these chemicals are resistant to degradation and bioaccumulate in the food chain. Little is known, however, about DDE toxicity during the early stages of neural development. The results of the present study demonstrate that DDE induced a caspase-3-dependent apoptosis and caused the global DNA hypomethylation in mouse embryonic neuronal cells. This study also provided evidence for DDE-isomer-non-specific alterations of retinoid X receptor alpha (RXRalpha)- and retinoid X receptor beta (RXRbeta)-mediated intracellular signaling, including changes in the levels of the receptor mRNAs and changes in the protein levels of the receptors. DDE-induced stimulation of RXRalpha and RXRbeta was verified using selective antagonist and specific siRNAs. Co localization of RXRalpha and RXRbeta was demonstrated using confocal microscopy. The apoptotic action of DDE was supported at the cellular level through Hoechst 33342 and calcein AM staining experiments. In conclusion, the results of the present study demonstrated that the stimulation of RXRalpha- and RXRbeta-mediated intracellular signaling plays an important role in the propagation of DDE-induced apoptosis during early stages of neural development. PMID- 26563998 TI - Is standing postural control more impaired in young patients with hip disarticulation than transfemoral amputation? A pilot study. PMID- 26563999 TI - Personalizing cardiac regenerative therapy: At the heart of Pim1 kinase. AB - During cardiac aging, DNA damage and environmental stressors contribute to telomeric shortening and human cardiac progenitor cells acquire a senescent phenotype that leads to decreased stem cell function. Reversion of this phenotype through genetic modification is essential to advance regenerative therapy. Studies in the cardiac specific overexpression and subcellular targeting of Pim1 kinase demonstrate its influence on regeneration, proliferation, survival, metabolism and senescence. The cardioprotective effects of Pim1 modification can be picked apart and enhanced by targeting the kinase to distinct subcellular compartments, allowing for selection of specific phenotypic traits after molecular modification. In this perspective, we examine the therapeutic implications of Pim1 to encourage the personalization of cardiac regenerative therapy. PMID- 26564000 TI - TLR4/TIRAP polymorphisms are associated with progression and survival of patients with symptomatic myeloma. AB - Myeloma cells thrive in an environment of sustained inflammation, which impacts the development and evolution of the disease, as well as drug resistance. We evaluated the impact of genetic polymorphisms in the Toll-like receptor 4 (TLR4) pathway, which have been implicated in different inflammatory responses in the outcomes of patients with symptomatic multiple myeloma (MM) who have received contemporary therapies. We found that the presence of single nucleotide polymorphisms (SNPs) in both the TLR4 and toll/interleukin-1 receptor (TIR) associated protein (TIRAP) genes was associated with lower response to primary therapy mainly for patients who received immunomodulatory drugs but not in patients treated with bortezomib-based therapies. Furthermore, TIRAP SNP was associated with a significantly shorter progression-free survival and overall survival, independently of other prognostic factors, such as age, transplant, International Staging System stage, lactate dehydrogenase and cytogenetics. This is the first study to demonstrate the effect of SNPs in TLR4/TIRAP in MM. Our data indicate that genetic variability in the immune system may be associated with different responses to antimyeloma therapies and may be a critical component affecting the natural history of the disease, providing the basis for further investigation of the role of these pathways in myeloma. PMID- 26564001 TI - Prevalence and underdiagnosis of airway obstruction among middle-aged adults in northern France: The ELISABET study 2011-2013. AB - INTRODUCTION: Airway obstruction (AO), mainly due to chronic obstructive pulmonary disease (COPD) in adults, is a major cause of mortality and poor quality of life. However, few data are available for France. This study was designed to calculate the prevalence AO among middle-aged adults in northern France, explore the associated risk factors and evaluate the underdiagnosis. METHODS: The Enquete Littoral Souffle Air Biologie Environnement (ELISABET) was a cross-sectional study of a representative sample of 3276 adults aged from 40 to 64 in two urban areas in northern France (Lille and Dunkirk). Participants filled out a questionnaire and performed spirometry testing, without a reversibility test. RESULTS: The age-standardized estimated prevalence [95% confidence interval] of AO was 16.0% [13.9; 17.9] in Lille and 13.7% [11.7; 15.7] in Dunkirk with the Global initiative for chronic Obstructive Lung Disease (GOLD) definition and 10.8% [9.2; 12.5] and 9.5% [7.9; 11.2] respectively with the lower limit of normal calculated with the Global Lung Initiative (GLI) 2012 equations. AO was associated with age, male gender, tobacco consumption and low body mass index. The underdiagnosis rate was greater than 70%. Previously undiagnosed participants with AO displayed more respiratory symptoms compared with participants without AO and less than participants with previously diagnosed AO. CONCLUSION: The prevalence of AO in northern France ranged from 9.5 to 16.0%, depending on the centre and definition used. The high underdiagnosis rate observed here suggests that greater efforts should be made to identify individuals presenting with the symptoms and/or risk factors associated with AO. PMID- 26564002 TI - Synthesis of urea in cometary model ices and implications for Comet 67P/Churyumov Gerasimenko. AB - Urea is considered a fundamental building block in prebiotic chemistry. Its formation on early Earth has not yet been explained satisfactorily and exogenous delivery has been considered. We report on the synthesis along with the first online and in situ identification of urea after exposing inorganic ices to ionizing radiation. PMID- 26564003 TI - Elevated levels of endothelial-derived microparticles, and serum CXCL9 and SCGF beta are associated with unstable asymptomatic carotid plaques. AB - Endothelial microparticles (EMPs) are released from dysfunctional endothelial cells. We hypothesised that patients with unstable carotid plaque have higher levels of circulating microparticles compared to patients with stable plaques, and may correlate with serum markers of plaque instability and inflammation. Circulating EMPs, platelet MPs (PMPs) and inflammatory markers were measured in healthy controls and patients undergoing carotid endarterectomy. EMP/PMPs were quantified using flow cytometry. Bioplex assays profiled systemic inflammatory and bone-related proteins. Immunohistological analysis detailed the contribution of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. EMPs and PMPs were significantly higher in patients with carotid stenosis (>= 70%) compared to controls, with no differences between asymptomatic vs symptomatic patients. Asymptomatic patients with unstable plaques exhibited higher levels of EMPs, CXCL9 and SCGF-beta compared to those with stable plaques. CXCL9, and SCGF-beta were detected within all plaques, suggesting a contribution to both localised and systemic inflammation. Osteopontin and osteoprotegerin were significantly elevated in the symptomatic vs asymptomatic group, while osteocalcin was higher in asymptomatic patients with stable plaque. All plaques exhibited calcification, which was significantly greater in asymptomatic patients. This may impact on plaque stability. These data could be important in identifying patients at most benefit from intervention. PMID- 26564004 TI - Lobular neoplasia detected in MRI-guided core biopsy carries a high risk for upgrade: a study of 63 cases from four different institutions. AB - There are certain criteria to recommend surgical excision for lobular neoplasia diagnosed in mammographically detected core biopsy. The aims of this study are to explore the rate of upgrade of lobular neoplasia detected in magnetic resonance imaging (MRI)-guided biopsy and to investigate the clinicopathological and radiological features that could predict upgrade. We reviewed 1655 MRI-guided core biopsies yielding 63 (4%) cases of lobular neoplasia. Key clinical features were recorded. MRI findings including mass vs non-mass enhancement and the reason for biopsy were also recorded. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ in subsequent surgical excision. The overall rate of lobular neoplasia in MRI-guided core biopsy ranged from 2 to 7%, with an average of 4%. A total of 15 (24%) cases had an upgrade, including 5 cases of invasive carcinoma and 10 cases of ductal carcinoma in situ. Pure lobular neoplasia was identified in 34 cases, 11 (32%) of which had upgrade. In this group, an ipsilateral concurrent or past history of breast cancer was found to be associated with a higher risk of upgrade (6/11, 55%) than contralateral breast cancer (1 of 12, 8%; P=0.03). To our knowledge, this is the largest series of lobular neoplasia diagnosed in MRI-guided core biopsy. The incidence of lobular neoplasia is relatively low. Lobular neoplasia detected in MRI-guided biopsy carries a high risk for upgrade warranting surgical excision. However, more cases from different types of institutions are needed to verify our results. PMID- 26564005 TI - Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-kappaB regulatory genes. AB - Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm with a variable and unpredictable clinical course. The genetic alterations that drive tumorigenesis in follicular dendritic cell sarcoma are largely unknown. One recent study performed BRAF sequencing and found V600E mutations in 5 of 27 (19%) cases. No other recurrent genetic alterations have been reported. The aim of the present study was to identify somatic alterations in follicular dendritic cell sarcoma by targeted sequencing of a panel of 309 known cancer-associated genes. DNA was isolated from formalin-fixed paraffin-embedded tissue from 13 cases of follicular dendritic cell sarcoma and submitted for hybrid capture-based enrichment and massively parallel sequencing with the Illumina HiSeq 2500 platform. Recurrent loss-of-function alterations were observed in tumor suppressor genes involved in the negative regulation of NF-kappaB activation (5 of 13 cases, 38%) and cell cycle progression (4 of 13 cases, 31%). Loss-of function alterations in the NF-kappaB regulatory pathway included three cases with frameshift mutations in NFKBIA and two cases with bi-allelic loss of CYLD. Both cases with CYLD loss were metastases and carried concurrent alterations in at least one cell cycle regulatory gene. Alterations in cell cycle regulatory genes included two cases with bi-allelic loss of CDKN2A, one case with bi-allelic loss of RB1, and one case with a nonsense mutation in RB1. Last, focal copy number gain of chromosome 9p24 including the genes CD274 (PD-L1) and PDCD1LG2 (PD L2) was noted in three cases, which represents a well-described mechanism of immune evasion in cancer. These findings provide the first insight into the unique genomic landscape of follicular dendritic cell sarcoma and suggest shared mechanisms of tumorigenesis with a subset of other tumor types, notably B-cell lymphomas. PMID- 26564006 TI - Concomitant loss of SMARCA2 and SMARCA4 expression in small cell carcinoma of the ovary, hypercalcemic type. AB - Small cell carcinoma of the ovary, hypercalcemic type is an aggressive tumor generally affecting young women with limited treatment options. Mutations in SMARCA4, a catalytic subunit of the SWI/SNF chromatin remodeling complex, have recently been identified in nearly all small cell carcinoma of the ovary, hypercalcemic type cases and represent a signature molecular feature for this disease. Additional biological dependencies associated with small cell carcinoma of the ovary, hypercalcemic type have not been identified. SMARCA2, another catalytic subunit of the SWI/SNF complex mutually exclusive with SMARCA4, is thought to be post-translationally silenced in various cancer types. We analyzed 10 archival small cell carcinoma of the ovary, hypercalcemic type cases for SMARCA2 protein expression by immunohistochemistry and found that SMARCA2 expression was lost in all but one case. None of the 50 other tumors that primarily or secondarily involved the ovary demonstrated concomitant loss of SMARCA2 and SMARCA4. Deep sequencing revealed that this loss of SMARCA2 expression is not the result of mutational inactivation. In addition, we established a small cell carcinoma of the ovary, hypercalcemic type patient derived xenograft and confirmed the loss of SMARCA2 in this in vitro model. This patient-derived xenograft model, established from a recurrent tumor, also had unexpected mutational features for this disease, including functional mutations in TP53 and POLE. Taken together, our data suggest that concomitant loss of SMARCA2 and SMARCA4 is another hallmark of small cell carcinoma of the ovary, hypercalcemic type-a finding that offers new opportunities for therapeutic interventions. PMID- 26564007 TI - Gliomatosis peritonei: a clinicopathologic and immunohistochemical study of 21 cases. AB - Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial tissue in the peritoneum. We retrospectively evaluated 21 patients with gliomatosis peritonei and studied their clinicopathologic features and immunophenotype. The patients' ages ranged from 5 to 42 years (median, 19 years). Their primary ovarian tumors consisted of immature teratoma (n=14), mixed germ cell tumors (n=6), and mature teratoma with a carcinoid tumor (n=1). Gliomatosis peritonei was diagnosed at the same time as primary ovarian neoplasm in 16 patients and secondary surgery in 5 patients. Also, 11 of 21 patients had metastatic immature teratoma (n=4), metastatic mature teratoma (n=2), or both (n=5). One patient developed glioma arising from gliomatosis peritonei. Seventeen patients had follow-up information and were alive with no evidence of disease (n=13), alive with disease (n=3), or alive with an unknown disease status (n=1). The follow-up durations ranged from 1 to 229 months (mean, 49 months; median, 23 months). Immunohistochemistry results demonstrated that SOX2 was expressed in all cases of gliomatosis peritonei and glioma with tissue available (nine of nine cases), whereas OCT4 and NANOG were negative in all cases with available tissue (eight of eight cases). In conclusion, both gliomatosis peritonei and glioma arising from it show a SOX2+/OCT4-/NANOG- immunophenotype. These findings demonstrated that gliomatosis peritonei is associated with favorable prognosis, although it is important to rule out potentially associated immature teratoma and malignant transformation. SOX2 may have an important role in the development of gliomatosis peritonei. PMID- 26564008 TI - Measurement properties of adult quality-of-life measurement instruments for eczema: a systematic review. AB - BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has identified quality of life (QoL) as a core outcome domain to be evaluated in every eczema trial. It is unclear which of the existing QoL instruments is most appropriate for this domain. Thus, the aim of this review was to systematically assess the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in adult eczema. METHODS: We conducted a systematic literature search in PubMed and Embase identifying studies on measurement properties of adult eczema QoL instruments. For all eligible studies, we assessed the adequacy of the measurement properties and the methodological quality with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis summarizing findings from different studies was the basis to assign four degrees of recommendation (A-D). RESULTS: A total of 15 articles reporting on 17 instruments were included. No instrument fulfilled the criteria for category A. Six instruments were placed in category B, meaning that they have the potential to be recommended depending on the results of further validation studies. Three instruments had poor adequacy in at least one required adequacy criterion and were therefore put in category C. The remaining eight instruments were minimally validated and were thus placed in category D. CONCLUSIONS: Currently, no QoL instrument can be recommended for use in adult eczema. The Quality of Life Index for Atopic Dermatitis (QoLIAD) and the Dermatology Life Quality Index (DLQI) are recommended for further validation research. PMID- 26564009 TI - Changes in Food Choices of Participants in the Special Diabetes Program for Indians-Diabetes Prevention Demonstration Project, 2006-2010. AB - INTRODUCTION: American Indians/Alaska Natives (AI/ANs) have a disproportionately high rate of type 2 diabetes. Changing food choices plays a key role in preventing diabetes. This study documented changes in the food choices of AI/ANs with diagnosed prediabetes who participated in a diabetes prevention program. METHODS: The Special Diabetes Program for Indians-Diabetes Prevention Demonstration Project implemented the evidence-based Diabetes Prevention Program (DPP) lifestyle intervention in 36 health care programs nationwide, engaging 80 AI/AN communities. At baseline, at 30 days post-curriculum, and at the first annual assessment, participants completed a sociodemographic survey and 27-item food frequency questionnaire and underwent a medical examination assessing fasting blood glucose (FBG), blood pressure, body mass index (BMI), low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides. Multiple linear regressions were used to assess the relationship between temporal changes in food choice and other diabetes risk factors. RESULTS: From January 2006 to July 2010, baseline, post-curriculum, and first annual assessments were completed by 3,135 (100%), 2,046 (65%), and 1,480 (47%) participants, respectively. An increase in healthy food choices was associated initially with reduced bodyweight, BMI, FBG, and LDL and increased physical activity. At first annual assessment, the associations persisted between healthy food choices and bodyweight, BMI, and physical activity. CONCLUSION: AI/AN adults from various tribal and urban communities participating in this preventive intervention made sustained changes in food choices and had reductions in diabetes risk factors. The outcomes demonstrate the feasibility and effectiveness of translating the DPP lifestyle intervention to community-based settings. PMID- 26564010 TI - Consumption of Alcoholic Beverages and Liquor Consumption by Michigan High School Students, 2011. AB - INTRODUCTION: Excessive alcohol consumption was responsible for approximately 4,300 annual deaths in the United States among people younger than 21 from 2006 through 2010. Underage drinking cost the United States $24.6 billion in 2006. Previous studies have shown that liquor is the most common type of alcohol consumed by high school students. However, little is known about the types of liquor consumed by youth or about the mixing of alcohol with energy drinks. METHODS: The 2011 Michigan Youth Tobacco Survey was used to assess usual alcohol beverage consumption and liquor consumption and the mixing of alcohol with energy drinks by Michigan high school students. Beverage preferences were analyzed by demographic characteristics and drinking patterns. RESULTS: Overall, 34.2% of Michigan high school students consumed alcohol in the past month, and 20.8% reported binge drinking. Among current drinkers, liquor was the most common type of alcohol consumed (51.2%), and vodka was the most prevalent type of liquor consumed by those who drank liquor (53.0%). The prevalence of liquor consumption was similar among binge drinkers and nonbinge drinkers, but binge drinkers who drank liquor were significantly more likely than nonbinge drinkers to consume vodka and to mix alcohol with energy drinks (49.0% vs 18.2%, respectively). CONCLUSIONS: Liquor is the most common type of alcoholic beverage consumed by Michigan high school students; vodka is the most common type of liquor consumed. Mixing alcohol and energy drinks is common, particularly among binge drinkers. Community Guide strategies for reducing excessive drinking (eg, increasing alcohol taxes) can reduce underage drinking. PMID- 26564011 TI - Association Between Student Body Mass Index and Access to Sports Drinks in Minnesota Secondary Schools, 2012-2013. AB - This ecologic study evaluated the association between school policy allowing students to purchase sports drinks from school vending machines and school stores and student body mass index (BMI). Data were from surveillance surveys of Minnesota secondary schools (n = 238) and students (n = 59,617), administered in 2012 and 2013, respectively. We used generalized linear models to assess the association between policies and mean age- and sex-adjusted BMI percentile. In adjusted multivariate analysis, school policy was positively associated with BMI percentile (P = .005). School policy restricting student access to sports drinks at school may contribute to decreasing consumption of sport drinks among school aged youth and improving student weight outcomes in this population. PMID- 26564012 TI - Health Promotion Interventions for Low-Income Californians Through Medi-Cal Managed Care Plans, 2012. AB - INTRODUCTION: Prevention is the most cost-effective approach to promote population health, yet little is known about the delivery of health promotion interventions in the nation's largest Medicaid program, Medi-Cal. The purpose of this study was to inventory health promotion interventions delivered through Medi Cal Managed Care Plans; identify attributes of the interventions that plans judged to have the greatest impact on their members; and determine the extent to which the plans refer members to community assistance programs and sponsor health promoting community activities. METHODS: The lead health educator from each managed care plan was asked to complete a 190-item online survey in January 2013; 20 of 21 managed care plans responded. Survey data on the health promotion interventions with the greatest impact were grouped according to intervention attributes and measures of effectiveness; quantitative data were analyzed using descriptive statistics. RESULTS: Health promotion interventions judged to have the greatest impact on Medi-Cal members were delivered in various ways; educational materials, one-on-one education, and group classes were delivered most frequently. Behavior change, knowledge gain, and improved disease management were cited most often as measures of effectiveness. Across all interventions, median educational hours were limited (2.4 h), and median Medi-Cal member participation was low (265 members per intervention). Most interventions with greatest impact (120 of 137 [88%]) focused on tertiary prevention. There were mixed results in referring members to community assistance programs and investing in community activities. CONCLUSION: Managed care plans have many opportunities to more effectively deliver health promotion interventions. Establishing measurable, evidence-based, consensus standards for such programs could facilitate improved delivery of these services. PMID- 26564013 TI - Systematic Review of Programs Treating High-Need and High-Cost People With Multiple Chronic Diseases or Disabilities in the United States, 2008-2014. AB - INTRODUCTION: Finding ways to provide better and less expensive health care for people with multiple chronic conditions or disability is a pressing concern. The purpose of this systematic review was to evaluate different approaches for caring for this high-need and high-cost population. METHODS: We searched Medline for articles published from May 31, 2008, through June 10, 2014, for relevant studies. Articles were considered eligible for this review if they met the following criteria: included people with multiple chronic conditions (behavioral or mental health) or disabilities (2 or more); addressed 1 or more of clinical outcomes, health care use and spending, or patient satisfaction; and compared results from an intervention group with a comparison group or baseline measurements. We extracted information on program characteristics, participant characteristics, and significant (positive and negative) clinical findings, patient satisfaction, and health care use outcomes. For each outcome, the number of significant and positive results was tabulated. RESULTS: Twenty-seven studies were included across 5 models of care. Of the 3 studies reporting patient satisfaction outcomes, 2 reported significant improvements; both were randomized controlled trials (RCTs). Of the 14 studies reporting clinical outcomes, 12 reported improvements (8 were RCTs). Of the 13 studies reporting health care use and spending outcomes, 12 reported significant improvements (2 were RCTs). Two models of care - care and case management and disease management - reported improvements in all 3 outcomes. For care and case management models, most improvements were related to health care use. For the disease management models, most improvements were related to clinical outcomes. CONCLUSIONS: Care and case management as well as disease management may be promising models of care for people with multiple chronic conditions or disabilities. More research and consistent methods are needed to understand the most appropriate care for these high-need and high-cost patients. PMID- 26564014 TI - Caring for People With Multiple Chronic Conditions. PMID- 26564015 TI - Formulation Development, Physicochemical Characterization and In Vitro-In Vivo Drug Release of Vaginal Films. AB - PURPOSE: The purpose of this study was formulation and optimization of vaginal film formulation containing abacavir (ABC), a potent nucleoside reverse transcriptase inhibitor. METHODS: Vaginal films were prepared by solvent evaporation method using hydroxypropyl methylcellulose (HPMC) blended with polyvinyl pyrrolidone (PVP). Various physicochemical parameters of the prepared films such as drug content, thickness, tensile strength, percentage elongation at break, drug polymer interaction, swelling capacity, folding endurance, bio adhesion, pH, and moisture content were evaluated with morphological studies. In vitro release study and in vivo release study were also performed. RESULTS: Films exhibited favorable physicochemical properties. The in vitro study showed that HPMC-PVP combination can control the release of abacavir through vaginal films with higher amount of PVP in the formulation resulting in an enhanced drug release rate. During the in vivo study in rabbits, systemic absorption of the drug was noted and the films remained intact for long in vagina without causing any sort of irritations. CONCLUSION: Thus, in a nutshell, the findings of our experimental work indicate that such films can be considered as a novel drug carrier system for the treatment of AIDS and other sexually transmitted diseases (STDs), and are suitable for local as well as systemic effects. PMID- 26564016 TI - Monochorionic quadramniotic and triamniotic pregnancies following single embryo transfers: two case reports and a review of the literature. AB - PURPOSE: The purpose of this study is to report two cases of monozygotic quadruplet and triplet pregnancies following single embryo transfer (ET). METHODS: A 29-year-old woman and a 34-year-old woman underwent ART treatment in two affiliated University based ART units. The first woman underwent ICSI with day 3 embryo biopsy for pre-implantation genetic diagnosis (PGD) followed by day 4 transfer, which resulted in a monochorionic quadramniotic (MCQA) quadruplet pregnancy. The second woman underwent conventional IVF with transfer of a single blastocyst, which resulted in a monochorionic triamniotic (MCTA) triplet pregnancy. RESULTS: The first patient underwent successful selective foetal reduction at 16 + 3 and 17 + 4 weeks of gestation. Two healthy twin girls were delivered by elective caesarean section at 35 + 6 weeks of gestation. The second patient underwent successful selective foetal reduction at 14 + 1 weeks of gestation. The remaining monochorionic diamniotic (MCDA) twins are well at the time of writing this article. CONCLUSIONS: To our knowledge, these cases represent the first case of viable MCQA pregnancy following single ET in the world and the third case of a viable MCTA pregnancy following conventional IVF with single ET. Several factors including blastocyst stage transfer and zona pellucida manipulation have been thought to contribute to monozygotic twinning in the context of ART. These two cases add to the growing literature of monozygotic multiple pregnancies following ART. PMID- 26564017 TI - The prevalence of hepatitis A virus and parvovirus B19 in source-plasma donors and whole blood donors in China. AB - AIMS: To compare the prevalence of hepatitis A virus (HAV) and human parvovirus B19 (B19V) between source-plasma (SP) donors and whole blood (WB) donors. BACKGROUND: In China, source plasma is in severe shortage while plasma recovered from WB is in surplus. Thus, the government is considering transferring the recovered plasma (RP) to produce plasma derivatives. HAV and B19V are two pathogens threatening the safety of plasma-based derivatives. However, there is no data about if transferring of the RP to produce plasma derivatives will increase the risk of HAV and B19V infection. Thus, we compared the prevalence of HAV and B19V between SP donors and WB donors in this study. METHODS: A total of 5030 samples from SP donors and 5040 samples from WB donors were collected. All the samples were tested for HAV RNA and B19V DNA and tested for HAV IgM by enzyme linked immunosorbent assay (ELISA). RESULTS: The prevalence of B19V DNA was 0.06% (95% confidence interval (CI), 0-0.09%) in WB donors and 0.079% (95% CI, 0-0.12%) in SP donors, respectively. No significant difference was found in the prevalence of B19V DNA between SP donors and WB donors. The prevalence of anti-HAV IgM in SP donors was 0.079% whereas no WB donor sample was found anti-HAV IgM reactive. CONCLUSIONS: The transfer of RP to producing plasma derivatives will not increase the risk of transmission of HAV and B19 through plasma products. PMID- 26564018 TI - Treatment for dysphagia (swallowing difficulties) in hereditary ataxia. AB - BACKGROUND: Hereditary ataxias are a heterogeneous group of disorders resulting in progressive inco-ordination. Swallowing impairment, also known as dysphagia, is a common and potentially life threatening sequel of disease progression. The incidence and nature of dysphagia in these conditions is largely unknown. The loss of an effective and safe swallow can dramatically affect the health and well being of an individual. Remediation of difficulties of eating and drinking is an important goal in the clinical care of people with hereditary ataxia. OBJECTIVES: To assess the effects of interventions for swallowing impairment (dysphagia) in people with hereditary ataxias. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, PsycINFO, and the Education Resources Information Center (ERIC) on 14 September 2015. We also searched Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts, and Trials Registries on 24 September 2015. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) and quasi-RCTs that compared treatments for hereditary ataxia with placebo or no treatment. We only included studies measuring dysphagia. DATA COLLECTION AND ANALYSIS: Three review authors (ES, KJ, MK) independently screened all titles and abstracts. In the event of any disagreement or uncertainty over the inclusion of a particular paper, the review authors planned to meet and reach consensus. MAIN RESULTS: We identified no RCTs from the 519 titles and abstracts screened. We excluded papers primarily for not including participants with a hereditary ataxia (that is, being focused on other neurological conditions), being theoretical reviews rather than intervention studies, or being neither randomised nor quasi-randomised trials.We identified five papers of various design that described treatment for dysphagia, or improvement to swallow as a by-product of treatment, in people with hereditary ataxia. None of these studies were RCTs or quasi-RCTs. AUTHORS' CONCLUSIONS: There is an absence of any significant evidence supporting the use of any dysphagia intervention in hereditary ataxia. The lack of evidence highlights the critical need for well-controlled treatment trials in the field. PMID- 26564019 TI - Longitudinal associations between conduct problems and depressive symptoms among girls and boys with early conduct problems. AB - Youth with conduct problems (CP) may experience high rates of depressive symptoms (DS). However, little is known about the direction of the longitudinal associations between CP and DS in this specific population. Although girls with CP appear at greater risk than boys for presenting comorbid depression, empirical research on gender differences in these associations is even sparser. The current study used autoregressive latent trajectory models to compare four perspectives with hypotheses regarding the longitudinal associations between CP and DS, while taking into account the evolution of both problems. We also examined gender differences in the longitudinal associations. A total of 345 children (40.6 % female) presenting with a high level of CP in early elementary school (mean age at study inception = 8.52; SD = .94) were evaluated annually over a four-year period (5 measurement time points). The results revealed that CP and DS were quite stable over time. Moreover, CP and DS showed strong covariation at each measurement time point, but only one significant positive cross-lagged association between the two processes, indicating that higher levels of DS at time 3 were associated with higher levels of CP 1 year later. No differences were observed in the longitudinal associations between CP and DS in boys and girls. Given the comorbidity and stability of CP and DS, these findings suggest that DS should be systematically evaluated among children with early clinically significant CP, and treatment plans should include interventions aimed at both CP and DS among children who present with both types of problems. PMID- 26564021 TI - Transdiagnostic heterogeneity, hierarchical dimensional models, and societal, cultural, and individual differences in the developmental understanding of psychopathology. PMID- 26564020 TI - Effect of socioeconomic status on psychosocial problems in 5- to 6-year-old preterm- and term-born children: the ABCD study. AB - This study aimed at analysing the association between socioeconomic status (SES) and psychosocial problems in preterm- and term-born children. Scores of mothers and teachers on the Strengths and Difficulties Questionnaire (SDQ) regarding 217 preterm-born children (<37 weeks' gestation, mean 34 weeks) were compared with 4336 term-born children in the Amsterdam Born Children and their Development (ABCD) cohort at age 5-6 years. Associations between SDQ scores and SES (maternal education and perceived income adequacy) were examined with multivariate linear regression analysis. The mean mother-reported total difficulties score was significantly higher for preterm children (6.1 +/- 4.7) than for term children (5.2 +/- 4.1). After covariate adjustment, this difference was 0.5 (95 % CI 0.0 1.0). For preterm children 16.1 % of the mothers reported psychosocial problems compared with 10.1 % for term children. Lower maternal education and lower income adequacy were significantly related to higher SDQ scores of mothers and teachers. Differences in mothers' SDQ score between preterm and term children were larger in the high-education (Delta0.9, 95 % CI 0.2-1.5) and high-income group (Delta0.9, 95 % CI 0.3-1.6). No significant differences were found between preterm and term children in the SDQ scores reported by teachers. Low level of maternal education and inadequate income showed a much stronger association with psychosocial problems than preterm birth. No combined effect of low SES and preterm birth was found. This study corroborates the evidence for the strength of the disadvantageous effects of low SES on early psychosocial development. PMID- 26564022 TI - A biomechanical approach to distal radius fractures for the emergency radiologist. AB - Distal radius fractures are the most common upper extremity fracture and account for approximately one sixth of all fractures treated in US emergency departments. These fractures are associated with significant morbidity and have a major economic impact. Radiographic evaluation of distal radius fractures is frequently performed in the emergency department setting, has a profound impact on initial management, and is essential to assessing the quality and relative success of the initial reduction. While the most appropriate definitive management of distal radius fractures remains controversial, overarching treatment principles reflect distal radius injury mechanisms and biomechanics. An intuitive understanding of the biomechanics of the distal radius and of common mechanisms of injury informs and improves the emergency radiologist's ability to identify key imaging findings with important management implications and to communicate the critical information that emergency physicians and orthopedic surgeons need to best manage distal radius fractures. PMID- 26564023 TI - Quality of life of patients with fibrodysplasia ossificans progressiva. AB - INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by episodes of acute pain and heterotopic ossification of soft tissue, and progressively limited physical function and social participation. OBJECTIVE: We aimed to determine the impact of FOP on quality of life, specifying areas or dimensions most affected. MATERIALS AND METHODS: This was a transverse observational study; patients with FOP were assessed using the Short Form 36. Questionnaire results were obtained using Quality Metric software and analyzed using frequency distribution, percentages and measures of central tendency. RESULTS: Eight patients, mean age 30.2 years, were included. The physical dimension was the most affected, with an average of 25.5 points. The most representative items were impaired function and physical role. Physical pain was found with an average of 44.5 points. The best scores were reported in the areas of emotional role and mental health, with an average of 79 and 76 respectively. CONCLUSIONS: FOP is a severely disabling disease, generating a significant deterioration in quality of life secondary to progressive deterioration in physical abilities. The findings of this study demonstrate good self-rated health of participants. PMID- 26564025 TI - Impact of glomerular filtration rate in colchicine toxicity. PMID- 26564024 TI - Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial. AB - Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient. PMID- 26564026 TI - Successful cutting balloon angioplasty in a child with resistant renal artery stenosis. AB - BACKGROUND: Although renovascular hypertension is a rare disease, it is associated with 5-10% of cases of childhood hypertension. It is a potentially treatable cause of hypertension, and is often caused by renal artery stenosis (RAS). The most common cause of RAS in children is fibromuscular dysplasia (FMD). The options for treating RAS depend on the location, severity and abnormality underlying the condition. CASE PRESENTATION: A previously healthy 7-year-old Korean boy presented to our clinic with hypertension and headache. Renal ultrasonography and multi-detector computed tomography (MDCT) showed severe focal stenosis at the middle portion of the left renal artery (LRA) and multiple collateral vessels. Percutaneous balloon angioplasty was performed as an initial treatment, but yielded unsatisfactory results. The presence of intimal-type FMD was suspected based on his clinical features, angiographic appearance, and resistance to percutaneous transluminal renal angioplasty. Thereafter, his blood pressure was normalized using antihypertensive medication. Follow-up multi detector computed tomography at 11 years of age showed persistent severe stenosis of the LRA. After unsuccessful attempts to perform balloon angioplasty, 3.5-mm cutting balloon angioplasty (CBA) was performed and yielded satisfactory results. He was discharged without any medication. At 1 year and 6 months after the intervention, he has been normotensive and had not required any antihypertensive medication. CONCLUSION: The author describes a case of resistant RAS that was detected on MDCT and successfully treated using percutaneous (CBA). Although cutting balloon angioplasty is useful in many clinical conditions, including the current case, clinicians should carefully consider the associated risk of arterial disruption and pseudoaneurysm formation. PMID- 26564027 TI - Time-Domain Filtering of Metasurfaces. AB - In general electromagnetic response of each material to a continuous wave does not vary in time domain if the frequency component remains the same. Recently, it turned out that integrating several circuit elements including schottky diodes with periodically metallised surfaces, or the so-called metasurfaces, leads to selectively absorbing specific types of waveforms or pulse widths even at the same frequency. These waveform-selective metasurfaces effectively showed different absorbing performances for different widths of pulsed sine waves by gradually varying their electromagnetic responses in time domain. Here we study time-filtering effects of such circuit-based metasurfaces illuminated by continuous sine waves. Moreover, we introduce extra circuit elements to these structures to enhance the time-domain control capability. These time-varying properties are expected to give us another degree of freedom to control electromagnetic waves and thus contribute to developing new kinds of electromagnetic applications and technologies, e.g. time-windowing wireless communications and waveform conversion. PMID- 26564028 TI - Glycemic and non-glycemic targets in younger and older North Indian subjects with type 2 diabetes in a Tertiary care hospital: A 10 year's retrospective data analysis. AB - BACKGROUND: Although optimizing glycemic and non-glycemic targets reduced micro- and macro-vascular complications in type 2 diabetes, multiple barriers hinder turning evidence into practice. Mounting evidence suggests that those with onset of disease in early or mid-adult life, compared with those with onset at an older age, may have a more severe disease course and worse glycemic control. AIMS & OBJECTIVE: We tested the hypothesis that those diagnosed at younger age would have worse glycemic control, even after adjustment for duration of diabetes, higher BMI and other known risk factors for worse glycemic control. MATERIALS & METHODS: A cross-sectional analysis of 560 type 2 diabetic subjects from North Indian populace in the year 1999-2012 who reported to endocrine clinic was performed. Sixty patients did not report in the successive year and final data analyses were done in 500 patients attending clinic regularly over a period of 10 years for evaluation of glycemic and non-glycemic targets. They were followed up at 3 monthly intervals with all patients undergoing anthropometric measurement (BMI (weight in kg/height in m(2)), diet and lifestyle advice by a diabetic educator and consultation by endocrinologist. Fasting and postprandial plasma glucose, A1c (3 monthly), besides evaluation of SMBG that was performed in 50% of these patients regularly. Fasting lipids, S. creatinine and microalbuminuria were assessed annually and blood pressure recoding was done at each visit. The treatment was modified as per the investigation reports. We classified age at diabetes diagnosis as younger (<60 years) vs older (>=60 years). The primary outcome of interest was HbA1c >=9%. Secondary outcomes were HbA1c >=8% to <9% and HbA1c >=7% to <8%. RESULTS: After adjustment for sex, duration of diabetes, hyperglycemic medications, BMI, co-morbid conditions, age <60 years at diagnosis remains significantly associated with greater odds of HbA1c >=9% [OR 0.95(0.84 1.07)], HbA1c >=8% to <9% [OR 1.04(0.93-1.15)] and HbA1c >=7% to <8% [OR 1.05(0.85-1.17)] for female sex. Seventy two (72.7%) of patients <60 years achieved BP <140/90mmHg (p<0.001) as compared to 62.3% of patients >=60 years who achieved BP <150/90mmHg (p<0.001) and LDL-cholesterol <100mg/dl in 33.7% patients and 39.1% respectively (p<0.002). CONCLUSION: Younger age (<60 years) at type 2 diabetes diagnosis is significantly associated with worse subsequent glycemic control and lipid control, as younger patients at diagnosis have fewer competing co-morbidities and complications. As patient-centeredness is a priority in type 2 diabetes care, safe, aggressive and individualized treatment could benefit this higher-risk group. PMID- 26564029 TI - The Arabidopsis CROWDED NUCLEI genes regulate seed germination by modulating degradation of ABI5 protein. AB - In Arabidopsis, the phytohormone abscisic acid (ABA) plays a vital role in inhibiting seed germination and in post-germination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, along with AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI (CRWN) proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA controlled seed germination by regulating the degradation of ABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstream of ABI5. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degradation in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination. PMID- 26564030 TI - An Optimal Set of Flesh Points on Tongue and Lips for Speech-Movement Classification. AB - PURPOSE: The authors sought to determine an optimal set of flesh points on the tongue and lips for classifying speech movements. METHOD: The authors used electromagnetic articulographs (Carstens AG500 and NDI Wave) to record tongue and lip movements from 13 healthy talkers who articulated 8 vowels, 11 consonants, a phonetically balanced set of words, and a set of short phrases during the recording. We used a machine-learning classifier (support-vector machine) to classify the speech stimuli on the basis of articulatory movements. We then compared classification accuracies of the flesh-point combinations to determine an optimal set of sensors. RESULTS: When data from the 4 sensors (T1: the vicinity between the tongue tip and tongue blade; T4: the tongue-body back; UL: the upper lip; and LL: the lower lip) were combined, phoneme and word classifications were most accurate and were comparable with the full set (including T2: the tongue-body front; and T3: the tongue-body front). CONCLUSION: We identified a 4-sensor set--that is, T1, T4, UL, LL--that yielded a classification accuracy (91%-95%) equivalent to that using all 6 sensors. These findings provide an empirical basis for selecting sensors and their locations for scientific and emerging clinical applications that incorporate articulatory movements. PMID- 26564031 TI - Complete Genome Sequences of Two Japanese Eel Endothelial Cell-Infecting Virus Strains Isolated in Japan. AB - Japanese eel endothelial cell-infecting virus (JEECV) causes viral endothelial cell necrosis of eel (VECNE), resulting in severe economic losses in eel aquaculture in Japan. Here, we report the complete genome sequences of two new JEECV strains isolated from farmed Japanese eels. PMID- 26564032 TI - Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhi Isolate PM016/13 from Untreated Well Water Associated with a Typhoid Outbreak in Pasir Mas, Kelantan, Malaysia. AB - Salmonella enterica subsp. enterica serovar Typhi is a human-restricted pathogen that causes typhoid fever. Even though it is a human-restricted pathogen, the bacterium is also isolated from environments such as groundwater and pond water. Here, we describe the genome sequence of the Salmonella enterica subsp. enterica serovar Typhi PM016/13 which was isolated from well water during a typhoid outbreak in Kelantan, Malaysia, in 2013. PMID- 26564033 TI - Full-Length Genome Sequences of Senecavirus A from Recent Idiopathic Vesicular Disease Outbreaks in U.S. Swine. AB - Since July 2015, vesicular lesions affecting growing pigs and sows accompanied with neonatal mortality have been reported in multiple U.S. states. Senecavirus A has been consistently detected from these cases. The complete genome sequences of 3 recent U.S. Senecavirus A isolates were determined to further characterize this virus. PMID- 26564034 TI - Genome Sequence of Bacillus anthracis Larissa, Associated with a Case of Cutaneous Anthrax in Greece. AB - We report the genome sequence of Bacillus anthracis strain Larissa, isolated from a diseased sheep associated with a human case of cutaneous anthrax in Central Greece from 2012. Genome sequence analysis of strain Larissa may aid in describing phylogenetic relationships of B. anthracis isolates in Southeastern European countries. PMID- 26564035 TI - Complete Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhi Isolate B/SF/13/03/195 Associated with a Typhoid Carrier in Pasir Mas, Kelantan, Malaysia. AB - We report here the complete genome sequence of Salmonella enterica subsp. enterica serovar Typhi B/SF/13/03/195 obtained from a typhoid carrier, who is a food handler in Pasir Mas, Kelantan. PMID- 26564036 TI - A Novel Member of Chitinophagaceae Isolated from a Human Peritoneal Tumor. AB - Peritoneal tumors from a rare malignancy, pseudomyxoma peritonei, frequently contain bacteria. Evidence suggests that tumor-associated bacteria contribute to pseudomyxoma peritonei development and/or progression. One unique isolate (PMP191F) was characterized via whole-genome sequencing using the Illumina MiSeq platform. PMP191F shows similarities to the Chitinophaga, Niastella, and Flavitalea genera. PMID- 26564037 TI - Draft Genome Sequence of the Pandoraea apista LMG 16407 Type Strain. AB - Pandoraea species, in particular Pandoraea apista, are opportunistic, multidrug resistant pathogens in persons with cystic fibrosis (CF). To aid in understanding the role of P. apista in CF lung disease, we used Illumina MiSeq and nanopore MinION technology to sequence the whole genome of the P. apista LMG 16407(T). PMID- 26564038 TI - Draft Genome Sequence of Bacillus amyloliquefaciens XK-4-1, a Plant Growth Promoting Endophyte with Antifungal Activity. AB - Here, we report the draft genome sequence of a bacterial plant-growth-promoting endophyte, Bacillus amyloliquefaciens XK-4-1, which consists of one circular chromosome of 3,941,805 bp with 3,702 coding sequences (CDSs). The data presented highlight multiple sets of functional genes associated with its plant-beneficial characteristics. PMID- 26564039 TI - Genome Sequence of a Clinical Klebsiella pneumoniae Sequence Type 6 Strain. AB - We report here the genome sequence of Klebsiella pneumoniae CH1034, a sequence type 6 (ST6) strain isolated in 2012 from a central venous catheter of a hospitalized patient. PMID- 26564040 TI - Draft Genome Sequence of Bacillus tequilensis Strain FJAT-14262a. AB - Bacillus tequilensis FJAT-14262a is a Gram-positive rod-shaped bacterium. Here, we report the 4,038,551-bp genome sequence of B. tequilensis FJAT-14262a, which will provide useful information for genomic taxonomy and phylogenomics of Bacillus. PMID- 26564041 TI - Complete Genome Sequence of Klebsiella pneumoniae Strain HKUOPLC, a Cellulose Degrading Bacterium Isolated from Giant Panda Feces. AB - We report here the complete genome sequence of Klebsiella pneumoniae strain HKUOPLC, isolated from a giant panda fecal sample collected from Ocean Park, Hong Kong. The complete genome of this bacterium may contribute to the discovery of efficient cellulose-degrading pathways. PMID- 26564042 TI - Whole-Genome Sequence of Mycobacterium bovis BCG-1 (Russia). AB - BCG vaccine (Mycobacterium bovis BCG-1 [Russia]) is the most important component of tuberculosis prophylaxis in Russia. This study represents the complete genome sequence and genetic characteristics of M. bovis BCG-1 (Russia), which has been used to manufacture BCG vaccine in Russia and in some other countries. PMID- 26564043 TI - Genome Sequence of Hydrocarbon-Degrading Cronobacter sp. Strain DJ34 Isolated from Crude Oil-Containing Sludge from the Duliajan Oil Fields, Assam, India. AB - We report here the 4,856,096-bp draft genome sequence of hydrocarbon-degrading Cronobacter sp. strain DJ34 isolated from crude oil-containing sludge from the Duliajan oil fields, India. DJ34 contains genes that mediate hydrocarbon degradation, metal resistance, and biosurfactant production. This is the first report of the genome sequence of Cronobacter sp. inhabiting an oil-contaminated environment. PMID- 26564044 TI - Complete Genome Sequence of a Human-Invasive Salmonella enterica Serovar Typhimurium Strain of the Emerging Sequence Type 213 Harboring a Multidrug Resistance IncA/C Plasmid and a blaCMY-2-Carrying IncF Plasmid. AB - Salmonella enterica subsp. enterica serovar Typhimurium strain 33676 was isolated in Mexico City, Mexico, from a patient with a systemic infection, and its complete genome sequence was determined using PacBio single-molecule real-time technology. Strain 33676 harbors an IncF plasmid carrying the extended-spectrum cephalosporin gene blaCMY-2 and a multidrug resistance IncA/C plasmid. PMID- 26564045 TI - Draft Genome Sequence of Desulfatitalea tepidiphila S28bFT. AB - Desulfatitalea tepidiphila S28bF(T) is a sulfate-reducing bacterium closely related to Desulfosarcina species. Here, the draft genome sequence of strain S28bF(T) is reported. PMID- 26564046 TI - Draft Genome Sequence of Burkholderia cenocepacia Strain 869T2, a Plant Beneficial Endophytic Bacterium. AB - An endophytic bacterium, Burkholderia cenocepacia 869T2, isolated from vetiver grass, has shown its abilities for both in planta biocontrol and plant growth promotion. Its draft genome sequence was determined to provide insights into those metabolic pathways involved in plant-beneficial activity. This is the first genome report for endophytic B. cenocepacia. PMID- 26564047 TI - Draft Genome Sequence of a Benzo[a]pyrene-Degrading Bacterium, Olleya sp. Strain ITB9. AB - Olleya sp. ITB9 is a benzo[a]pyrene-degrading bacterium, isolated from surface water near a waste treatment plant at Tokyo Bay, Japan. Here, we present the draft genome sequence of this strain, which consists of 58 contigs corresponding to 3.4 Mb and a G+C content of 31.2%. PMID- 26564048 TI - Complete Genome Sequences of an H5N1 Highly Pathogenic Avian Influenza Virus Isolated from Pigeon in China in 2012. AB - An avian influenza virus strain, A/pigeon/Hubei/RP25/2012 (H5N1), was isolated from pigeons in Hubei province, China. Phylogenetic analysis indicates that the HA gene belongs to clade 2.3.4 and the other internal genes present different recombination events. Information about the strain provides basic research data for epidemiological evidences for revealing influenza evolution. PMID- 26564049 TI - Draft Genome Sequence of Halostagnicola sp. A56, an Extremely Halophilic Archaeon Isolated from the Andaman Islands. AB - The first draft genome of Halostagnicola sp. A56, isolated from the Andaman Islands is reported here. The A56 genome comprises 3,178,490 bp in 26 contigs with a G+C content of 60.8%. The genome annotation revealed that A56 could have potential applications for the production of polyhydroxyalkanoate or bioplastics. PMID- 26564050 TI - Draft Genome Sequence of the Intermediate Rough Vaccine Strain Brucella abortus S19Deltaper Mutant. AB - Here, we report the genome sequence of the intermediate rough vaccine strain mutant, Brucella abortus S19Deltaper. The length of the draft genome was 3,271,238 bp, with 57.2% G+C content. A total of 3,204 protein-coding genes and 56 RNA genes were predicted. PMID- 26564051 TI - Complete Genome Sequence of a Novel Recombinant GII.Pe_GII.17 Norovirus Strain from Hong Kong in 2015. AB - The complete genome sequence of a novel recombinant GII.Pe_GII.17 norovirus strain, tentatively named GII.17 Hong Kong 2015, was determined. RNA-dependent RNA polymerase has 95.6% and 98.4% and viral protein 1 has 90.6% and 95.9% identity at the nucleotide and amino acid levels, respectively, to the closest sequences in GenBank. PMID- 26564052 TI - Complete Genome Sequence of the Drug-Naive Classical Staphylococcus aureus Strain FDA209P. AB - We report the complete genome sequence of the methicillin-sensitive Staphylococcus aureus (MSSA) strain FDA209P (ATCC 6538P and NCTC 7447). PMID- 26564053 TI - Draft Genome Sequences of Four Streptomyces Isolates from the Populus trichocarpa Root Endosphere and Rhizosphere. AB - Draft genome sequences for four Actinobacteria from the genus Streptomyces are presented. Streptomyces is a metabolically diverse genus that is abundant in soils and has been reported in association with plants. The strains described in this study were isolated from the Populus trichocarpa endosphere and rhizosphere. PMID- 26564054 TI - Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019. AB - We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to >=500 ug/ml. Two coding changes, in genes encoding a response regulator and an NAD(+) synthetase, arose during selection. PMID- 26564055 TI - Draft Genome Sequence of Thermus scotoductus Strain K1, Isolated from a Geothermal Spring in Karvachar, Nagorno Karabakh. AB - The 2,379,636-bp draft genome sequence of Thermus scotoductus strain K1, isolated from geothermal spring outlet located in the Karvachar region in Nagorno Karabakh is presented. Strain K1 shares about 80% genome sequence similarity with T. scotoductus strain SA-01, recovered from a deep gold mine in South Africa. PMID- 26564057 TI - Dopamine transporter scanning in the evaluation of patients with suspected Parkinsonism: a case-based user's guide. AB - Given the wide range of manifestations of parkinsonism and its mimics, the diagnosis may remain elusive or be misattributed in some patients. Dopamine transporter (DAT) single photon emission computed tomography (SPECT) (DaTscan), an imaging technique that probes the integrity of the presynaptic nigrostriatal system, can be useful in the evaluation of clinically complex parkinsonian disorders in the appropriate context and when adequately interpreted. Pearls and pitfalls in the use of DaTscan for the differential diagnosis of parkinsonisms are reviewed using a case-based format. While the DaTscan is no replacement for a careful neurological examination in ascertaining the likelihood of Parkinson disease or other parkinsonisms in most clinical scenarios, it can be useful in the assessment of disorders where an abducting resting tremor, a prominent postural tremor, or incongruent features are not sufficiently clear on exam to distinguish neurodegenerative parkinsonism from dystonia, drug-induced parkinsonism and functional (psychogenic) parkinsonism, respectively. PMID- 26564056 TI - CD4+CD25+ cells in multiple myeloma related renal impairment. AB - CD4(+)CD25(+) cells are critical regulators in almost all of the animal models of human organ-specific autoimmune diseases, transplant rejection and allergic diseases. We aimed to explore the role of CD4(+)CD25(+) cells in the pathogenesis of multiple myeloma (MM) related renal impairment (RI). Thirty patients with MM related RI and 30 healthy volunteers were studied. The number of CD4(+)CD25(+) cells was examined by flow cytometry. Clinical and laboratory data were collected from each subject. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4 and IL-6 were analyzed by ELISA. CD4(+)CD25(+) cells significantly decreased in MM related RI patients compared to the controls (P<0.05). CD4(+)CD25(+) cell number was negatively associated with blood urea nitrogen (BUN), supernatant IL 4, serum IL-6, monoclonal immunoglobulin and beta2-microglobulin, as well as bone marrow plasma cell percentage and proteinuria; whereas positively associated with estimated glomerular filtration rate (eGFR) (all P < 0.05). CD4(+)CD25(+) cells gradually decreased as the Clinic Stage increased. The number of CD4(+)CD25(+) cells reduced in MM related RI patients, and was correlated with disease severity. CD4(+)CD25(+) cells may play an important role in the pathogenesis of MM related RI. PMID- 26564058 TI - 405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence-guided stereotactic biopsy of brain tumors. AB - Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis. In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20-40 um between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy. PpIX signal attenuation through clinically relevant blood layers for 405 nm (violet) and 633 nm (red) excitation. PMID- 26564059 TI - Relationship between spontaneous sympathetic baroreflex sensitivity and cardiac baroreflex sensitivity in healthy young individuals. AB - Low baroreflex sensitivity (BRS) is associated with elevated cardiovascular risk. However, the evidence is based primarily on measurements of cardiac BRS. It cannot be assumed that cardiac or sympathetic BRS alone represent a true reflection of baroreflex control of blood pressure. The aim of this study was to examine the relationship between spontaneous sympathetic and cardiac BRS in healthy, young individuals. Continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made under resting conditions in 50 healthy individuals (18-28 years). Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified by plotting R-R interval against systolic pressure using the sequence method. Significant sympathetic BRSinc and cardiac BRS slopes were obtained for 42 participants. A significant positive correlation was found between sympathetic BRSinc and cardiac BRS (r = 0.31, P = 0.049). Among this group, significant sympathetic baroreflex slopes were obtained for 39 participants when plotting total MSNA against diastolic pressure. In this subset, a significant positive correlation was observed between sympathetic BRStotal and cardiac BRS (r = 0.40, P = 0.012). When males and females were assessed separately, these modest relationships only remained significant in females. Analysis by gender revealed correlations in the females between sympathetic BRSinc and cardiac BRS (r = 0.49, P = 0.062), and between sympathetic BRStotal and cardiac BRS (r = 0.57, P = 0.025). These findings suggest that gender interactions exist in baroreflex control of blood pressure, and that cardiac BRS is not appropriate for estimating overall baroreflex function in healthy, young populations. This relationship warrants investigation in aging and clinical populations. PMID- 26564060 TI - Contraction stimulates muscle glucose uptake independent of atypical PKC. AB - Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms lambda and zeta (PKC-lambda/zeta) have been shown to be necessary for insulin-, AICAR-, and metformin-stimulated glucose uptake in skeletal muscle, but not for treadmill exercise-stimulated muscle glucose uptake. To investigate if PKC lambda/zeta activity is required for contraction-stimulated muscle glucose uptake, we used mice with tibialis anterior muscle-specific overexpression of an empty vector (WT), wild-type PKC-zeta (PKC-zeta(WT)), or an enzymatically inactive T410A-PKC-zeta mutant (PKC-zeta(T410A)). We also studied skeletal muscle specific PKC-lambda knockout (MlambdaKO) mice. Basal glucose uptake was similar between WT, PKC-zeta(WT), and PKC-zeta(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC zeta(T410A) tibialis anterior muscles compared to WT or PKC-zeta(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of MlambdaKO mice than WT controls. Thus, loss of PKC lambda/zeta activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-lambda?zeta activity is not necessary for contraction-stimulated glucose uptake. PMID- 26564061 TI - Early structural remodeling and deuterium oxide-derived protein metabolic responses to eccentric and concentric loading in human skeletal muscle. AB - We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x-ray absorptiometry (DXA), and long-term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 +/- 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one-leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25-mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4 weeks. MPS was then quantified via GC-pyrolysis-IRMS over the 4-week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID-ECC: 1.42 vs. MID-CON: 1.4% day(-1); MTJ-ECC: 1.38 vs. MTJ-CON: 1.39% day(-1)). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode-independent correlation between MPS and MT (P = 0.07; R(2) = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined. PMID- 26564062 TI - Reduced vocal variability in a zebra finch model of dopamine depletion: implications for Parkinson disease. AB - Midbrain dopamine (DA) modulates the activity of basal ganglia circuitry important for motor control in a variety of species. In songbirds, DA underlies motivational behavior including reproductive drive and is implicated as a gatekeeper for neural activity governing vocal variability. In the zebra finch, Taeniopygia guttata, DA levels increase in Area X, a song-dedicated subregion of the basal ganglia, when a male bird sings his courtship song to a female (female directed; FD). Levels remain stable when he sings a less stereotyped version that is not directed toward a conspecific (undirected; UD). Here, we used a mild dose of the neurotoxin 6-hydroxydopamine (6-OHDA) to reduce presynaptic DA input to Area X and characterized the effects on FD and UD behaviors. Immunoblots were used to quantify levels of tyrosine hydroxylase (TH) as a biomarker for DA afferent loss in vehicle- and 6-OHDA-injected birds. Following 6-OHDA administration, TH signals were lower in Area X but not in an adjacent subregion, ventral striatal-pallidum (VSP). A postsynaptic marker of DA signaling was unchanged in both regions. These observations suggest that effects were specific to presynaptic afferents of vocal basal ganglia. Concurrently, vocal variability was reduced during UD but not FD song. Similar decreases in vocal variability are observed in patients with Parkinson disease (PD), but the link to DA loss is not well-understood. The 6-OHDA songbird model offers a unique opportunity to further examine how DA loss in cortico-basal ganglia pathways affects vocal control. PMID- 26564063 TI - Renal glucose release during hypoglycemia is partly controlled by sympathetic nerves - a study in pigs with unilateral surgically denervated kidneys. AB - Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 +/- 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 +/- 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients. PMID- 26564064 TI - Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension in NHE3 deficient mice with transgenic rescue of NHE3 in small intestines. AB - The role of Na(+/)H(+) exchanger 3 (NHE3) in the kidney in angiotensin II (ANG II)-induced hypertension remains unknown. The present study used global NHE3 deficient mice with transgenic rescue of the Nhe3 gene in small intestines (tgNhe3(-/-)) to test the hypothesis that genetic deletion of NHE3 selectively in the kidney attenuates ANG II-induced hypertension. Six groups of wild-type (tgNhe3(+/+)) and tgNhe3(-/-) mice were infused with either vehicle or ANG II (1.5 mg/kg/day, i.p., 2 weeks, or 10 nmol/min, i.v., 30 min), treated with or without losartan (20 mg/kg/day, p.o.) for 2 weeks. Basal systolic blood pressure (SBP) and mean intra-arterial blood pressure (MAP) were significantly lower in tgNhe3(-/-) mice (P < 0.01). Basal glomerular filtration rate, 24 h urine excretion, urinary Na(+) excretion, urinary K(+) excretion, and urinary Cl(-) excretion were significantly lower in tgNhe3(-/-) mice (P < 0.01). These responses were associated with significantly elevated plasma ANG II and aldosterone levels, and marked upregulation in aquaporin 1, the Na(+)/HCO3 cotransporter, the alpha1 subunit isoform of Na(+)/K(+)-ATPase, protein kinase Calpha, MAP kinases ERK1/2, and glycogen synthase kinase 3 alpha/beta in the renal cortex of tgNhe3(-/-) mice (P < 0.01). ANG II infusion markedly increased SBP and MAP and renal cortical transporter and signaling proteins in tgNhe3(+/+), as expected, but all of these responses to ANG II were attenuated in tgNhe3(-/-) mice (P < 0.01). These results suggest that NHE3 in the kidney is necessary for maintaining normal blood pressure and fully developing ANG II-dependent hypertension. PMID- 26564065 TI - Effects of urine composition on epithelial Na+ channel-targeted protease activity. AB - We examined human urinary proteolytic activity toward the Epithelial Sodium Channel (ENaC). We focused on two sites in each of alpha and gamma ENaC that are targets of endogenous and exogenous proteases. We examined the effects of ionic strength, pH and urinary H(+)-buffers, metabolic intermediates, redox molecules, and large urinary proteins. Monoatomic cations caused the largest effect, with sodium inhibiting activity in the 15-515 mEq range. Multivalent cations zinc and copper inhibited urinary proteolytic activity at concentrations below 100 MUmol/L. Similar to sodium, urea caused a 30% inhibition in the 0-500 mmol/L range. This was not observed with acetone and ethanol. Modulating urinary redox status modified activity with H2O2 stimulated and ascorbate inhibited activity. Minimal effects (<10%) were observed with caffeine, glucose, several TCA cycle intermediates, salicylic acid, inorganic phosphate, albumin, creatinine, and Tamm Horsfall protein. The cumulative activity of ENaC-cleaving proteases was highest at neutral pH, however, alpha and gamma proteases exhibited an inverse dependence with alpha stimulated at acidic and gamma stimulated at alkaline pH. These data indicate that ENaC-targeting urinary proteolytic activity is sensitive to sodium, urea and pH and changes in these components can modify channel cleavage and activation status, and likely downstream sodium absorption unrelated to changes in protein or channel density. PMID- 26564066 TI - Sigh-induced changes of breathing pattern in preterm infants. AB - Sighs are thought to play an important role in control of breathing. It is unclear how sighs are triggered, and whether preterm birth and lung disease influence breathing pattern prior to and after a sigh in infants. To assess whether frequency, morphology, size, and short-term variability in tidal volume (VT) before, during, and after a sigh are influenced by gestational age at birth and lung disease (bronchopulmonary dysplasia, BPD) in former preterm infants and healthy term controls measured at equivalent postconceptional age (PCA). We performed tidal breathing measurements in 143 infants during quiet natural sleep at a mean (SD) PCA of 44.8 (1.3) weeks. A total of 233 sighs were analyzed using multilevel, multivariable regression. Sigh frequency in preterm infants increased with the degree of prematurity and severity of BPD, but was not different from that of term controls when normalized to respiratory rate. After a sigh, VT decreased remarkably in all infants (paired t-test: P < 0.001). There was no major effect of prematurity or BPD on various indices of sigh morphology and changes in VT prior to or after a sigh. Short-term variability in VT modestly increased with maturity at birth and infants with BPD showed an earlier return to baseline variability in VT following a sigh. In early infancy, sigh-induced changes in breathing pattern are moderately influenced by prematurity and BPD in preterm infants. The major determinants of sigh-related breathing pattern in these infants remain to be investigated, ideally using a longitudinal study design. PMID- 26564067 TI - Calcium transport in bovine rumen epithelium as affected by luminal Ca concentrations and Ca sources. AB - The quantitative role of different segments of the gastrointestinal tract for Ca absorption, the respective mechanisms, and their regulation are not fully identified for ruminants, that is, cattle. In different in vitro experiments the forestomach wall has been demonstrated to be a major site for active Ca absorption in sheep and goats. In order to further clarify the role of the bovine rumen for Ca transport with special attention to luminal Ca concentrations, its ionic form, and pH, electrophysiological and unidirectional flux rate measurements were performed with isolated bovine rumen epithelial tissues. For Ca flux studies (Jms, Jsm) in vitro Ussing chamber technique was applied. Standard RT-PCR method was used to characterize TRPV6 and PMCA1 as potential contributors to transepithelial active Ca transport. At Ca concentrations of 1.2 mmol L(-1) on both sides of the tissues, Jms were higher than Jsm resulting under some conditions in significant Ca net flux rates (Jnet), indicating the presence of active Ca transport. In the absence of an electrical gradient, Jnet could significantly be stimulated in the presence of luminal short-chain fatty acids (SCFAs). Increasing the luminal Ca concentrations up to 11.2 mmol L(-1) resulted in significant increases in Jms without influencing Jsm. Providing Ca in its form as respective chloride, formate, or propionate salts there was no significant effect on Jms. No transcripts specific for Ca channel TRPV6 could be demonstrated. Our results indicate different mechanisms for Ca absorption in bovine rumen as compared with those usually described for the small intestines. PMID- 26564068 TI - Genetics of neurocutaneous disorders: basic principles of inheritance as they apply to neurocutaneous syndromes. AB - Neurocutaneous disorders vary widely in clinical presentation as well as genetic cause and inheritance pattern. Recent advancements in genetic research have identified many of the causal genes for neurocutaneous disorders, allowing families to receive genetic testing and genetic counseling to better understand carrier risks, recurrence risks for future generations, and reproductive options such as prenatal testing and preimplantation diagnosis. Examples of specific neurocutaneous disorders are utilized to illustrate the various inheritance patterns seen in this heterogeneous group of disorders, including autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, de novo, and somatic and germline mosaicism. PMID- 26564069 TI - Phenotype/genotype correlations in epidermal nevus syndrome as a neurocristopathy. AB - Epidermal nevus syndrome (ENS) is a term that encompasses several phenotypes defined by the association of an epidermal nevus with one or more congenital systemic anomalies, mainly ocular, osseous and cerebral. The two most frequent, keratinocytic nevus syndrome and linear sebaceous nevus syndrome, also correspond to the neurological phenotypes. They both exhibit overlapping and distinctive features but same etiology: post-zygotic mosaic mutations in RAS genes. Their pathogenesis is due to defective neural crest, further confirming that they are the same basic entity contradicting the concept that they are a group of heterogeneous syndromes with different etiologies. Both have been reported for more than a century. The sebaceous nevus, hallmark of linear sebaceous nevus syndrome, was defined by Jadassohn in 1895; the large number of subsequent contributors in defining this syndrome precludes the introduction of eponyms. Three other distinctive phenotypes within the spectrum of ENS with CNS involvement are CLOVES, SCALP and Heide's syndromes. Recognition of neurological phenotypes with multisystemic involvement should invoke multidisciplinary investigation and management. In some ENS phenotypes the association of melanocytic nevi with keratinocytic and sebaceous nevi, all sharing RAS mutations, predicts multisystemic involvement, in particular severe rickets and osseous anomalies. Phenotype is, therefore, the starting point for clinicians to guide genetic, neurological and other systemic investigations for patient management. The most frequent brain malformation in neurological phenotypes of ENS is hemimegalencephaly (HME). Epilepsy is the most frequent neurological symptom, in particular infantile spasms, with or without HME. The impact of neurological and systemic manifestations is related to onset and extent of the mutations. Timing of the mutation determines phenotype and severity. Proteus syndrome is a neurological phenotype of epidermal keratinocytic nevus syndrome not an independent, separate syndrome. PMID- 26564070 TI - Acquired neurocutaneous disorders. AB - A variety of neurologic diseases have cutaneous manifestations. These may precede, coincide with, or follow the neurologic findings. An array of autoimmune, genetic, and environmental factors play a role in expression and severity of the neurologic burden in these conditions. This chapter emphasizes congenital and genetic disorders, but we also discuss the pathophysiology and manifestation of various acquired neurocutaneous disorders with an emphasis Behcet's disease, dermatomyositis, Sjogren's syndrome, systemic lupus erythematosus, scleroderma, Parry-Romberg syndrome and Degos disease. PMID- 26564071 TI - Neurofibromatosis type 1. AB - Neurofibromatosis type 1 (NF1), previously known as von Recklinghausen disease, is a neurogenetic disorder distinct from neurofibromatosis type 2 (NF2). Approximately 1:2500 to 1:3500 individuals worldwide are affected, regardless of ethnicity or race. The classic manifestations of NF1 include cafe-au-lait macules, skinfold freckling, neurofibromas, brain tumors, iris hamartomas, and characteristic bony lesions. In addition, patients with NF1 are at increased risk for learning and intellectual disabilities, aqueductal stenosis, pheochromocytoma, vascular dysplasia, scoliosis, and cancer. In this chapter, we discuss the clinical and molecular features of NF1 as well as how insights into its underlying molecular pathophysiology have revealed new targets for therapeutic drug design. PMID- 26564072 TI - Neurofibromatosis type 2. AB - Type 2 neurofibromatosis (NF2) is an autosomal dominant disorder caused by mutations in the NF2 tumor suppressor gene NF2 on chromosome 22. Around 1 in 33000 people are born with an NF2 mutation although more than one-third of the 60% of de novo cases are not conceived with the mutation but this develops later in embryogenesis (mosaics). NF2 has a substantial effect on life expectancy and individuals with a constitutional truncating mutation have the worst prognosis. The vast majority of people with NF2 will develop bilateral vestibular schwannomas with many developing schwannomas on other cranial, spinal and peripheral nerves. Cranial and spinal meningiomas and intraspinal low grade indolent ependymomas are the other major tumor features. Cutaneous features can be subtle with only 70% having evidence of intracutaneous plaque-like schwannomas or subcutaneous lesions on peripheral nerves. Cafe-au-lait patches are more frequent than in the general population but in only around 1% will meet NIH criteria for NF1. PMID- 26564073 TI - Tuberous sclerosis complex. AB - Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and differentiation, resulting in hamartomas of various organs, tumor formation, and altered neuronal migration. The phenotype is highly variable. Most individuals have seizures, commonly including infantile spasms, and there is variable intellectual disability and autism. Neonates can present with cardiac failure due to intracardiac rhabdomyomas. The likelihood of renal angiomyolipomas increases with age, and renal disease is the most common cause of death in adults with TSC. Pulmonary involvement occurs predominantly in women and carries a high morbidity and mortality. TSC is inherited as an autosomal dominant trait, but spontaneous mutations are common. A mutation of either TSC1 on chromosome 9 or TSC2 on chromosome 16 leads to dysfunction of hamartin or tuberin, respectively. These two proteins form a functional complex that modulates the mammalian target of rapamycin (mTOR) pathway. Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications. Consensus statements guide identification and optimal management of many of the TSC-related complications at diagnosis and throughout the lifespan. A multidisciplinary approach is necessary for optimal management of individuals with TSC. PMID- 26564074 TI - Neurocutaneous melanosis. AB - Neurocutaneous melanosis is a rare neurocutaneous syndrome that is associated with a high rate of mortality early in life. Individuals with large cutaneous melanocytic nevi (LCMN) are at risk, especially when the nevi are posterior, midline and accompanied by satellite nevi. Disrupted production and migration of melanocytic precursors from neural crest likely are responsible. Although the cutaneous lesions are at risk for melanoma, the most likely source of morbidity and mortality comes from "benign" melanocytic proliferation in the brain or central nervous system melanoma. Seizures and hydrocephalus are the common neurologic manifestations and typically arise in the first years of life. Brain magnetic resonance imaging in infants before myelination has matured is most sensitive for detecting abnormal melanosis in the brain, which preferentially involves the leptomeninges, cerebellum and anterior temporal lobes. Treatment is symptomatic and death occurs in many within 3 years of onset of neurologic symptoms. This prognosis may limit the extent to which extensive procedures or interventions are undertaken. PMID- 26564075 TI - Basal cell nevus syndrome or Gorlin syndrome. AB - Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial. PMID- 26564076 TI - PTEN hamartoma tumor syndrome. AB - PTEN hamartoma tumor syndrome (PHTS) is the molecular diagnostic term describing patients with Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and other clinical presentations with germline mutation of the PTEN tumor suppressor gene. PHTS confers increased risks for specific malignancies, most notably breast, thyroid, renal, and endometrial cancers. Benign tumors are common, affecting a variety of tissues, and can range from subtle skin papules requiring no treatment to devastating vascular anomalies. There is also a broad range of neurodevelopmental effects, with some patients having no challenges and others with severe autism spectrum disorder and mental retardation. While most cases are inherited in a family for generations, following an autosomal dominant pattern, at least 10% and perhaps as many as 44% of cases are due to a new (de novo) mutation. Clinical presentations can vary dramatically from patient to patient, even among those in the same family. Features of this condition that may assist in diagnosis prior to cancer development can be subtle and difficult to recognize. This chapter will help the reader identify which patients should be referred for genetics evaluation and how to manage patients diagnosed with this rare condition. PMID- 26564078 TI - Sturge-Weber syndrome. AB - Sturge-Weber syndrome is the third most common neurocutaneous disorder, after neurofibromatosis and tuberous sclerosis, and impacts approximately 1 in 20000 live births. Sturge-Weber syndrome is not inherited, but rather occurs exclusively sporadically, in both males and females and in all races and ethnic backgrounds. Sturge-Weber syndrome presents at birth with a capillary malformation on the face (port-wine birthmark) with later diagnosis of abnormal vasculature in the eye and the brain which result in a range of complications. The underlying somatic mosaic mutation causing both Sturge-Weber syndrome and isolated port-wine birthmarks was recently discovered and is an activating mutation in GNAQ. When a newborn presents with a facial port-wine birthmark on the upper face, that child has a 15-50% risk of developing Sturge-Weber syndrome brain and/or eye involvement, depending on the extent of the birthmark, and close monitoring and appropriate screening is essential for early diagnosis and optimal treatment. Treatment options include laser therapy for lightening of the birthmark, eye drops and surgery for glaucoma management, and aggressive anticonvulsant treatment, low dose aspirin, and neurosurgery where necessary. Future possible treatments based upon new knowledge of the somatic mutation and downstream pathways are currently being considered and studied. PMID- 26564079 TI - PHACE(S) syndrome. AB - PHACE(S) syndrome is a neurocutaneous disorder of unknown etiology. The acronym refers to the commonest features of PHACE: posterior fossa malformations, large facial hemangiomas, cerebral arterial anomalies, cardiovascular anomalies, and eye anomalies. When ventral developmental defects such as sternal clefting or supraumbilical raphe occur, the PHACES acronym may be used. The hallmark feature of PHACE is the presence of one or more large facial infantile hemangiomas that occupy at least one facial segment. Infantile hemangiomas differ from the capillary malformation (port wine stain) of Sturge-Weber syndrome, and the arteriovenous malformation of Wyburn-Mason syndrome, distinguishing PHACE syndrome from other neurocutaneous disorders with red birthmarks. The true incidence of PHACE has not yet been established. Girls are more commonly affected than boys. Cerebral vascular anomalies are probably the most common extracutaneous feature. Given that several organ systems are involved, a multidisciplinary approach to disease surveillance and treatment is advised. PMID- 26564080 TI - Hereditary hemorrhagic telangiectasia. AB - Hereditary hemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that is characterized by multiple arteriovenous malformations (AVMs) involving the skin, mucosal surfaces, and internal organs. HHT has an age-dependent penetrance and usually initially presents with recurrent epistaxis followed by the characteristic telangiectasias of the face, oropharynx, and hands over time. Patients often have vascular malformations that involve their lungs, brain, spinal cord, and gastrointestinal tract as well, which are the main causes of morbidity in patients with HHT. The sequelae of visceral organ involvement include ischemic stroke, cerebral bacterial abscesses, intracranial hemorrhage, chronic hypoxia, dyspnea with exertion, pulmonary hypertension, high output heart failure, gastrointestinal bleeds and liver failure. PMID- 26564077 TI - Von Hippel-Lindau disease. AB - von Hippel-Lindau (VHL) disease is an inheritable condition with an incidence of 1 in 36000 live births. Individuals with VHL develop benign and malignant tumors including retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas (RCC), pheochromocytomas, pancreatic neuroendocrine tumors and endolymphatic sac tumors (ELSTs). VHL is caused by germline loss of function of the VHL gene on one allele at chromosome 3p25-26. A somatic "second hit" event leads to the loss of the other allele and tumor formation. Loss of VHL function in cells leads to increased expression and stabilization of hypoxia inducible factor (HIF). VHL protein/HIF pathway has been implicated in tumorigenesis for hemangioblastomas, RCC and other VHL tumors. Clinical examination, imaging, and genetic testing for VHL mutations confirm VHL disease. Management of VHL disease largely consists of surgical resection of symptomatic tumors (hemangioblastomas), tumors prone to metastasize (RCC larger than 3cm), or tumors causing hormonal symptoms (pheochromocytomas). Despite advances in early diagnosis and management of VHL disease, life expectancy for VHL patients remains low at 40-52 years. Secondary effects from VHL manifestations are mitigated by routine surveillance and early detection. In this chapter, we summarize the current state of knowledge in VHL disease. PMID- 26564081 TI - Ataxia telangiectasia. AB - Ataxia telangiectasia (AT) is an autosomal recessive multisystem genetic disorder caused by a mutation in the ATM gene encoding for the ATM protein. AT systemic manifestations include cutaneous telangiectasias, radiosensitivity, immune deficiency with recurrent sinopulmonary infections, and a tendency to develop lymphoid malignancies. These complications are explained by the major role played by ATM in DNA repair. AT is also the second most common childhood onset neurodegenerative disorder of the cerebellum, presenting with progressive ataxia and oculomotor apraxia and often accompanied by extrapyramidal movement disorders. Ataxia typically begins around the time children start to walk at about 1 year of age and leads to wheelchair dependence by the second decade of life. Cerebellar atrophy is evident on imaging after 2 years of life and is progressive. Abnormal DNA repair mechanisms do not entirely explain the pathophysiology in nondividing neurons. The nervous system involvement is better explained by the role ATM plays in antioxidative defense, mitochondrial homeostasis, and DNA chromatin packing. A better understanding of the underlying pathophysiologic mechanisms of this devastating disease may enable disease modifying treatments in the future. Meanwhile, treatment is mainly supportive and does not change the poor prognosis of the disease although it improves the patient's quality of life. PMID- 26564082 TI - Pseudoxanthoma elasticum. AB - Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish papules and plaques (pseudoxanthomas) and retinal angioid streaks. Although these findings may begin in childhood, the diagnosis is typically not made until the second or third decade after the skin and retinal findings become more prominent. Cerebrovascular complications include brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation. Intracranial hemorrhage can occur in the absence of aneurysm, and gastrointestinal hemorrhage is common. Peripheral arterial vascular disease can lead to intermittent leg claudication. A skin biopsy often demonstrates calcified elastic fibers, even in a mildly affected area of skin. The inheritance is autosomal recessive, although heterozygotes may exhibit some features of the disease. PXE is due to mutation of the ABCC6 gene on chromosome 16. There is no treatment, but certain lifestyle modifications may limit the complications. The potential for retinal hemorrhage has led to recommendations for limitations of contact sports or other activities that might facilitate eye trauma. Other recommendations include maintaining a normal lipid profile, avoidance of aspirin and nonsteroidal anti-inflammatory agents, and limiting dietary calcium intake. PMID- 26564083 TI - Blue bleb rubber nevus syndrome. AB - Vascular malformations are errors of development of vessels that occur during embryogenesis. They are rheologically divided into slow-flow (capillary, lymphatic, venous and combined) and fast-flow (arterial, arteriovenous, and combined) malformations. These congenital lesions grow proportionally with the patient and never spontaneously regress. Venous malformations (VM) are composed of ectatic venous-like channels. They are mainly sporadic but can be inherited as an autosomal pattern. Any tissue and organ can be affected. They can be isolated or part of syndromes. Blue rubber bleb naevus syndrome is characterized by multifocal rubbery cutaneous venous malformations, especially on palm and sole, that are associated with multiple gastrointestinal VM. Localized intravascular coagulopathy, with high D-dimer level and normal-to-low fibrinogen level, is commonly seen. As cerebral VM can also occur in this syndrome, brain MRI should be part of the screening of patients affected with BRBN. Management is often multidisciplinary and can include medical, interventional radiological and/or surgical treatment. PMID- 26564084 TI - Fabry disease. AB - Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for alpha-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Recent studies suggested a much higher incidence of mutations of the GLA gene, suggesting that this disorder is under-diagnosed. However, some of the gene variants may be benign. Although the etiology of Fabry disease has been known for many years, the mechanism by which the accumulating alpha-D-galactosyl moieties cause this multi organ disorder has only recently been studied and is yet to be completely elucidated. Specific therapy for Fabry disease has been developed in the last few years but its role in the management of the disorder is still being investigated. Fortunately, standard 'non-specific' medical and surgical therapy is effective in slowing deterioration or compensating for organ failure in patients with Fabry disease. PMID- 26564085 TI - Hutchinson-Gilford progeria syndrome. AB - Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, uniformly fatal, segmental "premature aging" disease in which children exhibit phenotypes that may give us insights into the aging process at both the cellular and organismal levels. Initial presentation in early childhood is primarily based on growth and dermatologic findings. Primary morbidity and mortality for children with HGPS is from atherosclerotic cardiovascular disease and strokes with death occurring at an average age of 14.6 years. There is increasing data to support a unique phenotype of the craniofacial and cerebrovascular anatomy that accompanies the premature aging process. Strokes in HGPS can occur downstream of carotid artery and/or vertebral artery occlusion, stenosis, and calcification, with prominent collateral vessel formation. Both large and small vessel disease are present, and strokes are often clinically silent. Despite the presence of multisystem premature aging, children with HGPS do not appear to have cognitive deterioration, suggesting that some aspects of brain function may be protected from the deleterious effects of progerin, the disease-causing protein. Based on limited autopsy material, there is no pathologic evidence of dementia or Alzheimer-type changes. In a transgenic mouse model of progeria with expression of the most common HGPS mutation in brain, skin, bone, and heart, there are distortions of neuronal nuclei at the ultrastructural level with irregular shape and severe invaginations, but no evidence of inclusions or aberrant tau in brain sections. Importantly, the nuclear distortions did not result in significant changes in gene expression in hippocampal neurons. This chapter will discuss both preclinical and clinical aspects of the genetics, pathobiology, clinical phenotype, clinical care, and treatment of HGPS, with special attention toward neurologic and cutaneous findings. PMID- 26564086 TI - Encephalocraniocutaneous lipomatosis. AB - Encephalocraniocutaneous lipomatosis (ECCL) is an unusual condition marked by characteristic dermatologic and neurologic findings presenting in a mosaic fashion. These are now being found to be due to specific genetic mutations. Traditionally, the diagnostic features include ocular dermoids, scalp changes, and spinal lipomas. While there are other similar diagnostic considerations, ECCL, is sufficiently distinct clinically to allow differentiation. Such information is of use when considering pathogenesis and in counseling. Consideration of possible associated clinical findings is key for correct clinical assessment and management. The condition highlights the need for a collaborative approach to diagnosis and management. Dermatology, ophthalmology, genetics, neurology, and neurosurgery can be engaged in the care of such patients. PMID- 26564087 TI - Incontinentia pigmenti (Bloch-Sulzberger syndrome). AB - Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome; OMIM #308300) is an X linked dominant neurocutaneous disorder with presumed male lethality. It is usually diagnosed in female newborns based on skin features (erythematous, vesicular, or bullous eruption in linear streaks). The skin lesions evolve into a verrucous stage, followed by atrophy and scarring, leaving linear areas of hypopigmentation and hyperpigmented macules in bizarre patterns following Blaschko's lines. Systemic and neurologic complications include focal seizures and hemorrhagic cerebral infarction in infants, and retinal vasculopathy leading to blindness. Hypodontia, conical or pegged teeth, and linear areas of alopecia persist into adulthood. IP is caused by mutation of the IKBKG/NEMO gene on Xq28. Deletion of exons 4 to 10 (NEMODelta4-10) accounts for about 80% of cases (familial and sporadic). NEMO mutation leads to loss of function of NF-kappaB, a critical protein that modulates cellular proliferation, apoptosis, and response to proinflammatory factors, leading to the characteristic features of IP. In female carriers, selective loss of cells expressing the mutant X-chromosome results in completely skewed X-inactivation in the majority of cases. Study of mouse models in which various components of the NF-kappaB pathway (including NEMO) have been knocked out has contributed significantly to our understanding of disease pathogenesis. PMID- 26564088 TI - Hypomelanosis of Ito. AB - Hypomelanosis of Ito, initially referred to as incontinentia pigmenti achromians, is a rare neurocutaneous disorder. Hypopigmented lesions following the lines of Blaschko are usually the presenting feature. Multiple organ systems can be involved including brain, musculoskeletal, cardiovascular, eyes, kidneys, and teeth. The neurologic complications can include seizures, hemimegalencephaly, developmental delay and abnormalities in tone. Genetic mosaicism is the most likely explanation for its inheritance. It must be distinguished from incontinentia pigmenti because at early stages, skin lesions can appear similar between the two conditions. Consensus recommendations for screening of associated extracutaneous conditions do not exist and management is symptomatic, but regular evaluation of somatic growth, neurodevelopment, endocrine status, eyes, and teeth should occur. Initial screening of renal function has also been recommended. Awareness of this disorder will allow for diagnosis, genetic counseling and appropriate screening. PMID- 26564089 TI - Epidermal nevus syndromes. AB - The term epidermal nevus syndrome (ENS) has been used to describe the association of epidermal hamartomas and extracutaneous abnormalities. Although many continue to use the term "ENS," it is now understood that this is not one disease, but rather a heterogeneous group with distinct genetic profiles defined by a common cutaneous phenotype: the presence of epidermal and adnexal hamartomas that are associated with other organ system involvement. One commonality is that epidermal nevi often follow the lines of Blaschko and it appears the more widespread the cutaneous manifestations, the greater the risk for extracutaneous manifestations. The majority of the extracutaneous manifestations involve the brain, eye, and skeletal systems. The CNS involvement is wide ranging and involves both clinical manifestations such as intellectual disability and seizures, as well as structural anomalies. Several subsets of ENS with characteristic features have been delineated including the nevus sebaceus syndrome, Proteus syndrome, CHILD syndrome, Becker's nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach given the potential for multisystem involvement. Of note, epidermal nevi have been associated with both benign and malignant neoplasms, and thus ongoing clinical follow-up is required. PMID- 26564090 TI - Lipoid proteinosis. AB - Lipoid proteinosis is a rare autosomal recessive disorder caused by mutations in ECM1, encoding extracellular matrix protein 1, a glycoprotein expressed in many organs and which has important protein-protein interactions in tissue homeostasis. Although the disease usually presents clinically with warty infiltration of the skin and mucous membranes and a hoarse voice, neuropsychological and neuropsychiatric abnormalities are often prominent features. There may be bean- or comma-shaped intracranial calcifications, often selectively affecting the amygdala. Patients with lipoid proteinosis therefore have been used as models for demonstrating physiologic and pathologic abnormalities of the amygdala with respect to fear processing, affect and cognition, anxiety and memory. Clinically, patients may also have epilepsy, especially involving the temporal lobes. Less common or rare disease associations are headache (including migraine), ataxia, dizziness, schizophrenia, generalized dystonia, transient brachiofacial paralysis, and intracerebral hemorrhage. Beyond the foci of calcification, the cause of the neurologic abnormalities in lipoid proteinosis is unknown, although the ECM1 protein can normally bind to various extracellular matrix proteins and glycosaminoglycans as well as certain enzymes, including matrix metalloproteinase 9. Loss of key protein-protein interactions may underscore some of the disease pathophysiology. There is currently no effective treatment for lipoid proteinosis and clinical care is largely supportive. PMID- 26564091 TI - Preface. PMID- 26564092 TI - Foreword. PMID- 26564093 TI - Comparison of the frequency of the growth hormone pseudogene between juvenile and adult female masu salmon Oncorhynchus masou. AB - The proportions of individual masu salmon Oncorhynchus masou whose genotypic and phenotypic sex differed were compared among juvenile and adult fish in three rivers, and genotypically male but phenotypically female individuals were observed 6-16% more often among adults than among juveniles. This suggests that during the transition from juvenile to adult, survival rates of genotypically male but phenotypically female individuals are higher than those of normal females. In contrast, genotypically female but phenotypically male individuals were only found in the juvenile period, which suggests that they exhibit a decreased survival rate in comparison with normal males. PMID- 26564094 TI - VRACs swallow platinum drugs. PMID- 26564095 TI - Gold Nanorod Rotary Motors Driven by Resonant Light Scattering. AB - Efficient and robust artificial nanomotors could provide a variety of exciting possibilities for applications in physics, biology and chemistry, including nanoelectromechanical systems, biochemical sensing, and drug delivery. However, the application of current man-made nanomotors is limited by their sophisticated fabrication techniques, low mechanical output power and severe environmental requirements, making their performance far below that of natural biomotors. Here we show that single-crystal gold nanorods can be rotated extremely fast in aqueous solutions through optical torques dominated by plasmonic resonant scattering of circularly polarized laser light with power as low as a few mW. The nanorods are trapped in 2D against a glass surface, and their rotational dynamics is highly dependent on their surface plasmon resonance properties. They can be kept continuously rotating for hours with limited photothermal side effects and they can be applied for detection of molecular binding with high sensitivity. Because of their biocompatibility, mechanical and thermal stability, and record rotation speeds reaching up to 42 kHz (2.5 million revolutions per minute), these rotary nanomotors could advance technologies to meet a wide range of future nanomechanical and biomedical needs in fields such as nanorobotics, nanosurgery, DNA manipulation and nano/microfluidic flow control. PMID- 26564096 TI - Body composition: Where and when. AB - The in vivo evaluation of body composition is essential in many clinical investigations, in order to accurately describe and monitor the nutritional status of a range of medical conditions and physiological processes, including sick and malnourished patients, pregnant women, breastfeeding women and the elderly, as well as in patients with cancer, osteoporosis and many other diseases. This research area is also important to the field of human nutrition and exercise physiology. Several research investigations have indicated the importance of measuring fat deposition in different body compartments, in order to gain a fuller understanding of the genetic factors that contribute to obesity, obesity-related disorders, such as dyslipidemia, and thereby to a fuller understanding of obesity associated cardio-metabolic disorders, with relevance to the relationship between body composition and energy expenditure. The spatial and temporal dimension, where and when, may influence the physiological relevance and the pathological implications of the fat composition of different body compartments, and, as such, is a new element to be considered when assessing body composition. PMID- 26564097 TI - Current status of fasciolosis in Vietnam: an update and perspectives. AB - Vietnam is recognized to be endemic for fasciolosis. However, most of the available publications have not been published in international journals. This review is based on national and international Vietnamese publications and highlights the current status of fasciolosis in Vietnam. It also provides some information available for neighbouring countries. Updated data on responsible species, distribution, transmission and control aspects are summarized. The central region of Vietnam is reported as being highly endemic for fasciolosis, with a high number of human patients (more than 20,000 in 2011). Fasciola gigantica is reported to be the main species in Vietnam. However, hybrids between F. gigantica and F. hepatica were identified. Both humans and animals are infected by the ingestion of raw vegetables and possibly contaminated drinking water. Three lymnaeid snail species (Austropeplea viridis, Radix auricularia and Radix rubiginosa) may act as intermediate hosts of Fasciola spp. However, due to the likely misidentification of snail species and cercariae during the past decade the critical analysis of published data is difficult. A better understanding of transmission aspects of fasciolosis would allow the implementation of preventive measures of this important neglected zoonotic disease. PMID- 26564098 TI - Tetraalkylammonium Salts as Hydrogen-Bonding Catalysts. AB - Although the hydrogen-bonding ability of the alpha hydrogen atoms on tetraalkylammonium salts is often discussed with respect to phase-transfer catalysts, catalysis that utilizes the hydrogen-bond-donor properties of tetraalkylammonium salts remains unknown. Herein, we demonstrate hydrogen-bonding catalysis with newly designed tetraalkylammonium salt catalysts in Mannich-type reactions. The structure and the hydrogen-bonding ability of the new ammonium salts were investigated by X-ray diffraction analysis and NMR titration studies. PMID- 26564099 TI - Strengthening training in rural practice in Germany: new approach for undergraduate medical curriculum towards sustaining rural health care. AB - CONTEXT: After decades of providing a dense network of quality medical care, Germany is facing an increasing shortage of medical doctors in rural areas. Current graduation rates of generalists do not counterbalance the loss due to retirement. Informed by international evidence, different strategies to ensure rural medical care are under debate, including innovative teaching approaches during undergraduate training. ISSUES: The University of Magdeburg in Saxony Anhalt was the first medical school in Germany to offer a rural elective for graduate students. During the 2014 summer semester, 14 medical students attended a two-weekend program in a small village in Northern Saxony-Anhalt that allowed them to become more familiar with a rural community and rural health issues. LESSONS LEARNED: The elective course raised a series of relevant topics for setting up rural practice and provided students with helpful insight into living and working conditions in rural practice. Preliminary evaluations indicate that the rural medicine course allowed medical students to reduce pre-existing concerns and had positive impact on their willingness to set up a rural medical office after graduation. Even short-term courses in rural practice can help reduce training-related barriers that prevent young physicians from working in rural areas. Undergraduate medical training is promising to attenuate the emerging undersupply in rural areas. PMID- 26564100 TI - Multipurpose Nature of Rapid Covalent Functionalization on Carbon Nanotubes. AB - In the vast field of functionalization routes to carbon nanoforms, the fulfillment of such critical requirements as quick and nonharsh methods, good dispersibility, introduction of reactive groups, short reaction time, and low cost can be quite challenging. Traditional thermally induced diazonium chemistry on single-walled carbon nanotubes (SWCNTs) is revisited by using commercial anilines and providing useful insight into the versatility of this approach. Functionalized SWCNTs with multiple controllable features, such as degree (and ratio) of coverage, orthogonalization, doping, and high water dispersibility, are obtained by introducing benzenesulfonic acid and benzylamine moieties. The scenario opens up an avenue to address relevant applications in which most functionalization methods could not be applied in a straightforward way. PMID- 26564101 TI - [Telephone consultations in a geriatrics clinic]. PMID- 26564102 TI - Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. AB - BACKGROUND AND PURPOSE: The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo. METHODS: This study was a prospective, randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Patients were treated with Cerebrolysin (30 mL/d) or a placebo (saline) once daily for 21 days, beginning at 24 to 72 hours after stroke onset. The patients also participated in a standardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset. The primary end point was the Action Research Arm Test score on day 90. RESULTS: The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann-Whitney estimator, 0.71; 95% confidence interval, 0.63-0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann-Whitney estimator, 0.62; 95% confidence interval, 0.58-0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated. CONCLUSIONS: Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke. Its safety was comparable with that of the placebo, suggesting a favorable benefit/risk ratio. Because this study was exploratory and had a relatively small sample size, the results should be confirmed in a large-scale, randomized clinical trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrialsregister.eu. Unique identifier: 2007-000870-21. PMID- 26564103 TI - Cytosolic Receptor Melanoma Differentiation-Associated Protein 5 Mediates Preconditioning-Induced Neuroprotection Against Cerebral Ischemic Injury. AB - BACKGROUND AND PURPOSE: Preconditioning with poly-l-lysine and carboxymethylcellulose (ICLC) provides robust neuroprotection from cerebral ischemia in a mouse stroke model. However, the receptor that mediates neuroprotection is unknown. As a synthetic double-stranded RNA, poly-ICLC may bind endosomal Toll-like receptor 3 or one of the cytosolic retinoic acid inducible gene-I-like receptor family members, retinoic acid-inducible gene-I, or melanoma differentiation-associated protein 5. Activation of these receptors culminates in type I interferons (IFN-alpha/beta) induction-a response required for poly-ICLC-induced neuroprotection. In this study, we investigate the receptor required for poly-ICLC-induced neuroprotection. METHODS: Toll-like receptor 3, melanoma differentiation-associated protein 5-, and IFN-promoter stimulator 1 deficient mice were treated with poly-ICLC 24 hours before middle cerebral artery occlusion. Infarct volume was measured 24 hours after stroke to identify the receptor signaling pathways involved in protection. IFN-alpha/beta induction was measured in plasma samples collected 6 hours after poly-ICLC treatment. IFN-beta deficient mice were used to test the requirement of IFN-beta for poly-ICLC induced neuroprotection. Mice were treated with recombinant IFN-alpha-A to test the role of IFN-alpha as a potential mediator of neuroprotection. RESULTS: Poly ICLC induction of both neuroprotection and systemic IFN-alpha/beta requires the cytosolic receptor melanoma differentiation-associated protein 5 and the adapter molecule IFN-promoter stimulator 1, whereas it is independent of Toll-like receptor 3. IFN-beta is not required for poly-ICLC-induced neuroprotection. IFN alpha treatment protects against stroke. CONCLUSIONS: Poly-ICLC preconditioning is mediated by melanoma differentiation-associated protein 5 and its adaptor molecule IFN-promoter stimulator 1. This is the first evidence that a cytosolic receptor can mediate neuroprotection, providing a new target for the development of therapeutic agents to protect the brain from ischemic injury. PMID- 26564104 TI - Reduced Nicotinamide Adenine Dinucleotide Phosphate, a Pentose Phosphate Pathway Product, Might Be a Novel Drug Candidate for Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Our previous study has defined a role of TP53-induced glycolysis and apoptosis regulator in neuroprotection against ischemic injury through increasing the flow of pentose phosphate pathway. We hypothesized that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) could be a novel drug for treatment of ischemic stroke. METHODS: The NADPH was given before, at the onset, or after stroke onset with single or repeated intravenous (mice and rats) or intraperitoneal injections (monkey). The short- and long-term therapeutic effects of NADPH were evaluated in male adult ICR mice (total=614) with transient middle cerebral artery occlusion, in male adult Sprague-Dawley rats (total=114) with permanent middle cerebral artery occlusion, and in male adult rhesus monkey (total=12) with thrombotic middle cerebral artery occlusion. RESULTS: Administration of NADPH led to a dramatic increase in the levels of ATP and reduced form of glutathione, whereas it decreased the levels of reactive oxygen species. NADPH significantly reduced infarct volume, improved poststroke survival, and recovery of neurological functions in mouse and rat models of stroke. Robust neuroprotection of a single dose of NADPH was seen when it was administered within 5 hours after reperfusion; however, repeat administration of NADPH twice a day for 7 days starting 24 hours after the onset of stroke also offered therapeutic effects. Pretreatment with NADPH also significantly improved the outcome of stroke insult. CONCLUSIONS: Administration of exogenous NADPH significantly protected neurons against ischemia/reperfusion-induced injury in 2 rodent stroke models. Thus, NADPH might be a promising drug candidate for treatment of ischemic stroke. PMID- 26564105 TI - Investigation of the origin of stromal and endothelial cells at the desmoplastic interface in xenograft tumor in mice. AB - Carcinoma-associated fibroblasts found at the interface between a tumor and the normal stroma play several roles in the development of cancer, including cancer initiation, growth, and progression, thereby also affecting patient prognosis. Although recent studies have focused on carcinoma-associated fibroblasts as potential treatment targets, the origin of these fibroblasts remains unclear. One theory suggests that these cells arise from tumor cells undergoing the epithelial mesenchymal transition, i.e., tumor cells transform into carcinoma-associated fibroblasts. Therefore, in this study, we aimed to elucidate the cellular origin of carcinoma-associated fibroblasts in a mouse xenograft model. Mice were transplanted with human lung cancer cells (H226 and A549 cells). After sacrifice, tumor masses and surrounding tissues were excised. Interestingly, the excised xenograft tissues contained a significant proportion of desmoplastic fibroblasts that exhibited strong expression of alpha-smooth muscle actin (SMA). Immunohistochemical staining with pan-cytokeratin, vimentin, beta-catenin, E cadherin, and CD34 showed no evidence of the epithelial-mesenchymal transition. Additional evaluation using dual-color silver in situ hybridization with dinitrophenyl-labeled human epidermal growth factor receptor 2 (HER2) and digoxigenin-labeled chromosome 17 centromere probes also showed similar results. In conclusion, our results revealed that the epithelial-mesenchymal transition may not occur in tumor xenograft models, regardless of evidence supporting this phenomenon in humans. PMID- 26564106 TI - Hyaline ring granuloma of vegetable: Report of two cases with histochemical and immunohistochemical study. AB - BACKGROUND: Peripheral hyaline ring granuloma is a rare lesion characterized by the presence of hyaline rings and multinucleated giant cells. Its pathogenesis is related to exogenous factors such as vegetal origin, resulting in foreign body reaction mediated by macrophages against cellulose particles. We report two cases: a 58-year-old male with a lesion in the maxillary alveolar mucosa measuring 1.0cm*1.0cm; and a 50-year-old female presenting a slight swelling in the alveolar mucosa, measuring 0.7cm*0.7cm and diagnosed as asymptomatic sessile nodule of fibrous consistency. Microscopic examination revealed a dense connective tissue with focal area of concentric hyaline collagen deposition and multinucleated giant cell granulomas of foreign body type. Immunohistochemical study was positive for anti-CD68/anti-alpha-SMA, confirming the foreign body reaction and vascular integrity. Histochemical analysis for PAS with and without diastase and van Gieson highlighted the vegetable exogenous origin of foreign material. Additionally, we performed a review of 7 cases published in the literature in the last 10 years. PMID- 26564107 TI - MTHFR C677T polymorphism and anatomopathological characteristics with prognostic significance in sporadic colorectal cancer. AB - Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation, repair and synthesis. The MTHFR C677T polymorphism is associated with decreased risk of CRC and increased sensitivity to 5-FU treatment. The present study addressed the relationship between this polymorphism and histopathological and immunohistochemical characteristics of prognostic significance in 50 patients from the Canary Islands. No differences were found between the MTHFR C677T genotypes with respect to tumor budding, tumor necrosis, desmoplastic fibrosis and tumoral eosinophilia. No significant differences were found in Ki-67, bcl-2 (cytoplasmic and nuclear), CD31, CD3+ T lymphocytes (both stromal and intraepithelial) and peritumoral CD20+ B lymphocytes. In carriers of the MTHFR CC variant, tumor margins were infiltrative more frequently (68.7%) than in CT+TT carriers (33.3%, p=0.03). In addition, wild-type CC genotype showed stromal CD20+ B lymphocytes (68.8%) more often than CT+TT carriers (33.3%, p=0.03). Both parameters indicate a better tumor prognosis when the MTHFR 677T variant is present. PMID- 26564108 TI - Weight fluctuation during adulthood and weight gain since breast cancer diagnosis predict multiple dimensions of body image among rural breast cancer survivors. AB - OBJECTIVE: Obesity and weight gain after breast cancer treatment are common among survivors, yet the relationship between weight and body image has received little attention. The purpose of the current study was to examine the relationship between current body mass index, weight gain since diagnosis, and largest weight fluctuation in adulthood with six dimensions of body image among overweight/obese breast cancer survivors. METHODS: The current study used data obtained from a weight control trial with 210 rural overweight/obese breast cancer survivors. Using data collected at baseline, multiple regression models were constructed to examine the relative association of the three weight variables with breast cancer specific dimensions of body image while controlling for demographic characteristics and cancer treatment-related variables. RESULTS: Largest weight fluctuation in adulthood significantly predicted overall body image (p = 0.01) and was associated with the three socially oriented dimensions of body image: social activity restriction, embarrassment about appearance, and sexuality (all ps = 0.01). Weight gain since diagnosis approached statistical significance in predicting overall body image (p = 0.05) and was associated with embarrassment about appearance (p = 0.03). Current body mass index was not significantly associated with overall body image when controlling for the other weight variables (p = 0.07) and was negatively associated with social activity restriction (p = 0.01) and sexuality (p = 0.01). CONCLUSIONS: Obese breast cancer survivors with a history of a large weight fluctuation in adulthood may be prone to poorer breast cancer-specific body image several years after treatment. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26564109 TI - A novel resource for studying function and dysfunction of alpha-synuclein: mouse lines for modulation of endogenous Snca gene expression. AB - Pathological modification of alpha-synuclein is believed to be an important event in pathogenesis of Parkinson's disease and several other neurodegenerative diseases. In normal cells this protein has been linked to many intracellular processes and pathways. However, neither normal function of alpha-synuclein in neuronal and certain other types of cells nor its exact role in the disease pathogenesis is well understood, which is largely due to limitations of animal models used for studying this protein. We produced and validated several novel mouse lines for manipulating expression of the endogenous Snca gene coding for alpha-synuclein. These include a line for conditional Cre-recombinase-driven inactivation of the gene; a line for conditional Flp-driven restoration of a neo cassete-blocked alpha-synuclein expression; a new line with a "clean" constituent knockout of the gene as well as a line carrying this knockout locus and Rosa26 stop-lacZ reporter locus linked at the same mouse chromosome 6. Altogether these lines represent a set of new useful tools for studies of alpha-synuclein normal function and the role of this protein in disease pathogenesis. PMID- 26564110 TI - Upper ureteric transitional cell carcinoma, extending to the renal pelvis, presenting as duodenal obstruction. AB - A 61-year-old man presented with weight loss, dysphagia and vomiting. A barium swallow revealed a duodenal obstruction at D3. CT of the abdomen and pelvis showed a left upper ureteric tumour extending to the renal pelvis compressing the duodenum and causing left-sided hydronephrosis. Cystoscopy and left-sided ureteroscopy proved difficult and were unable to visualise or biopsy the mass, but a left ureteric stent was placed. Laparoscopic biopsy of the mass was completed and histology revealed transitional cell carcinoma. The patient went on to receive palliative chemotherapy, which relieved the small bowel obstruction, and the patient was able to eat solid food 8 weeks later. This case highlights a previously unreported cause of duodenal obstruction. PMID- 26564111 TI - A healthy patient with bilateral frozen hips preceding bilateral frozen shoulders: a cautionary tale. AB - Adhesive capsulitis of the shoulder (frozen shoulder) is a common disease characterised by spontaneous onset of pain and restriction of movement, followed by 'thawing', with complete or near-complete resolution. Adhesive capsulitis of the hip has been reported in around a dozen patients. This report describes an otherwise-healthy middle-aged woman with apparent sequential resolving adhesive capsulitis of all four ball-and-socket joints over a 9-year period, initially affecting each hip and then each shoulder sequentially. The likely hip diagnosis became clear only retrospectively with development of the second frozen shoulder, 5 years after the first pain. All joints subsequently resolved within the expected timeframe and the patient remains healthy, other than having mild hypertension. This case illustrates that, when hip precedes shoulder involvement, there is the potential for the frozen hip to receive alternate diagnoses for which invasive open hip surgery could unnecessarily be recommended. PMID- 26564112 TI - Neck swelling after thyroidectomy: not always a haematoma. AB - We present a case of a patient who returned with a neck swelling 6 days following thyroidectomy and central neck compartment lymphadenectomy for suspected thyroid carcinoma. The initial clinical suspicion pointed to a haematoma, but a needle aspiration showed chyle. Chyle leak is a rare complication of thyroid surgery. In the described case, this was successfully managed conservatively with repeated aspirations and a low-fat diet. We discuss the aetiology, presentation and management of this complication. PMID- 26564113 TI - Not just another thunderclap headache: a case of isolated cortical vein thrombosis and subarachnoid haemorrhage. PMID- 26564114 TI - DPG-plus syndrome: new report of a rare entity. AB - Pituitary gland duplication is a particularly rare finding. Different theories have been proposed to explain its pathogenesis, however, this phenomenon is not yet totally understood. Recently, duplication of the pituitary gland (DPG)-plus syndrome has been described, associating DPG with other blastogenic defects. We present the clinical and imaging findings of a newborn girl with DPG, associated with multiple other midline anomalies, including a nasopharyngeal teratoma, palate cleft deformity, bifid nasal bridge, tongue and uvula, hypoplasia of the basis pontis and corpus callosum, duplication of the basilar artery and hypothalamic hamartoma. We describe our patient's multidisciplinary team approach and emphasise the importance of reporting upcoming cases, in order to give more insight into the understanding of this complex entity. PMID- 26564115 TI - Vertebral artery dissection in evolution found during chiropractic examination. AB - A 30-year-old woman presented to an emergency department with sudden onset of transient loss of left peripheral vision. Owing to a history of migraine headaches, she was released with a diagnosis of ocular migraine. Two days later, she sought chiropractic care for the chief symptom of severe neck pain. The chiropractor suspected the possibility of vertebral artery dissection (VAD). No manipulation was performed; instead, MR angiography (MRA) of the neck was obtained, which revealed an acute left VAD with early thrombus formation. The patient was placed on aspirin therapy. Repeat MRA of the neck 3 months later revealed resolution of the thrombus, without progression to stroke. This case illustrates the importance for all healthcare providers who see patients with neck pain and headache to be attentive to the symptomatic presentation of possible VAD in progress. PMID- 26564116 TI - Metastatic choriocarcinoma induced separate simultaneous intracerebral haemorrhages: a very rare occurrence and its novel association with Klinefelter syndrome. AB - Non-traumatic separate simultaneous intracerebral haemorrhages (SSIHs) are rare. Relevant aetiologies are diverse and their diagnosis challenging. We report a unique case of SSIH in an 18-year-old male with a background of previously undiagnosed testicular choriocarcinoma and Klinefelter syndrome. The patient was admitted to Auckland City Hospital with headaches, drowsiness and vomiting. A CT scan revealed SSIH in a background of tumorous lesions. His beta human chorionic gonadotropin titre was elevated at 355 000 IU/L. The SSIH and the associated tumorous lesions were acutely surgically resected and the patient started on bleomycin, etoposide and cisplatin combination chemotherapy with excellent results. In this article, we underline choriocarcinoma as a rare aetiology of SSIH and present an example of the clinical presentation, investigation and management of this very rare pathological entity. PMID- 26564117 TI - Atypical CML with massive splenic infarct: an extremely rare presentation. AB - We report a case of a 47-year-old man who presented with hepatosplenomegaly, anaemia and massive splenic infarct. A series of investigations led us to a diagnosis of atypical chronic myeloid leucaemia, a rare variety of a mixed myelodysplastic/myeloproliferative neoplasm. This is the first case of atypical CML presenting with massive splenic infarction. PMID- 26564118 TI - Sensorineural deafness following routine transurethral resection of the prostate. AB - A man in his 50s presented to a rural Australian emergency department with complete unilateral hearing loss following transurethral resection of the prostate. His hearing impairment progressed from 'muffled hearing' with tinnitus on emergence from anaesthesia, to total sensorineural deafness by day three. His surgery and anaesthesia were uncomplicated and he had remained normotensive throughout. He had no pre-existing auditory disease. He had received 240 mg of intravenous gentamicin intraoperatively for surgical prophylaxis. Renal function was normal. Brain imaging was negative for structural pathology, stroke and circulatory insufficiency. Ear nose and throat advised 7 days of oral corticosteroids, transtympanic dexamethasone and hyperbaric oxygen therapy. A working diagnosis of gentamicin-induced ototoxicity was applied. Intervention has proven unsuccessful and there is no possibility for rehabilitation. The patient is permanently disabled. PMID- 26564119 TI - Unusual mode of failure of intertrochanteric femur fracture fixation. AB - The dynamic hip screw fixation is a commonly used modality of treatment for intertrochanteric femur (ITF) fractures. Various modes of failure in an operated case of ITF fracture have been described. The most frequent mode of failure is screw cut-out through the head. Occurrence of mechanical failure is rare and usually involves the shaft of the plate. We describe an unusual case with failure at the barrel of the plate and hip screw. A middle-aged man with a previously operated ITF fracture presented with pain in the same hip. Radiographs revealed non-union of the fracture with an implant failure. Revision surgery was performed during which a unique mode of implant failure was found to have occurred. The barrel of the plate had broken resulting in a bent Richard's screw. This case underlines the importance of high stress failure in non-union as opposed to high cycle, low stress failure, which is more frequently seen. PMID- 26564120 TI - VIPoma with multiple endocrine neoplasia type 1 identified as an atypical gene mutation. AB - A 47-year-old man presented with persistent diarrhoea and hypokalaemia. CT revealed 4 pancreatic tumours that appeared to be VIPomas, because the patient had an elevated plasma vasoactive intestinal polypeptide level. MRI showed a low intensity area in the pituitary suggestive of a pituitary tumour, and a parathyroid tumour was detected by ultrasonography and 99Tc-MIBI scintigraphy. Given these results, the patient was diagnosed with multiple endocrine neoplasia type 1 (MEN1) and scheduled for surgery. MEN1 is an autosomal dominant disorder associated with MEN1 mutations. Genetic testing indicated that the patient had a MEN1 gene mutation; his 2 sons had the same mutations. Most MEN1 tumours are benign, but some pancreatic and thymic tumours could become malignant. Without treatment, such tumours would result in earlier mortality. Despite its rarity, we should perform genetic testing for family members of patients with MEN1 to identify mutation carriers and improve the patients' prognosis. PMID- 26564121 TI - Portal hypertensive gastropathy and gastric antral vascular ectasia. AB - Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are gastric mucosal lesions that mostly present as chronic anemia and rarely cause the acute gastrointestinal hemorrhage. Despite similar clinical manifestations, their pathophysiology and management are entirely different. PHG is seen exclusively in patients with portal hypertension, but GAVE can also be observed in patients with other conditions. Their diagnosis is endoscopic, and although generally each of them has a characteristic endoscopic appearance and distribution, there are cases in which the differential is difficult and must rely on histology. This review focuses on the management of both entities. The mainstay of management of PHG is based on portal-hypotensive pharmacological treatment while GAVE benefits from hormonal therapy, endoscopic Nd:YAG laser, and argon plasma coagulation. More invasive options should be reserved for refractory cases. PMID- 26564122 TI - Calibration Model for Apnea-Hypopnea Indices: Impact of Alternative Criteria for Hypopneas. AB - STUDY OBJECTIVE: To characterize the association among apnea-hypopnea indices (AHIs) determined using three common metrics for defining hypopnea, and to develop a model to calibrate between these AHIs. DESIGN: Cross-sectional analysis of Sleep Heart Health Study Data. SETTING: Community-based. PARTICIPANTS: There were 6,441 men and women age 40 y or older. MEASUREMENT AND RESULTS: Three separate AHIs have been calculated, using all apneas (defined as a decrease in airflow greater than 90% from baseline for >= 10 sec) plus hypopneas (defined as a decrease in airflow or chest wall or abdominal excursion greater than 30% from baseline, but not meeting apnea definitions) associated with either: (1) a 4% or greater fall in oxyhemoglobin saturation-AHI4; (2) a 3% or greater fall in oxyhemoglobin saturation-AHI3; or (3) a 3% or greater fall in oxyhemoglobin saturation or an event-related arousal-AHI3a. Median values were 5.4, 9.7, and 13.4 for AHI4, AHI3, and AHI3a, respectively (P < 0.0001). Penalized spline regression models were used to compare AHI values across the three metrics and to calculate prediction intervals. Comparison of regression models demonstrates divergence in AHI scores among the three methods at low AHI values and gradual convergence at higher levels of AHI. CONCLUSIONS: The three methods of scoring hypopneas yielded significantly different estimates of the apnea-hypopnea index (AHI), although the relative difference is reduced in severe disease. The regression models presented will enable clinicians and researchers to more appropriately compare AHI values obtained using differing metrics for hypopnea. PMID- 26564123 TI - A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease. AB - STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data. METHODS: One hundred nine newly diagnosed, drug-naive PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability. RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88). CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances. PMID- 26564124 TI - Altered Sleep Homeostasis in Rev-erbalpha Knockout Mice. AB - STUDY OBJECTIVES: The nuclear receptor REV-ERBalpha is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBalpha's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbalpha, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBalpha on the homeostatic regulation of sleep. METHODS: EEG/EMG signals were recorded in Rev erbalpha knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. RESULTS: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbalpha increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBalpha also in the brain. CONCLUSIONS: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBalpha to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. PMID- 26564125 TI - Changes in Sleep Duration and Sleep Timing Associated with Retirement Transitions. AB - STUDY OBJECTIVES: Investigate whether retirement transitions are associated with changes in sleep duration and sleep timing, and whether these associations are modified by age, sex, mental health, or circadian preference. METHODS: The Retirement and Sleep Trajectories (REST) study is a longitudinal study consisting of four annual mailed surveys that collected information about employment, sleep, and health. Differences in reported sleep duration, bedtime and wake time between successive surveys were calculated to estimate change over 1, 2, and 3 y. Linear regression models were used to estimate changes in these sleep parameters associated with retirement 1, 2, and 3 y posttransition. RESULTS: Retiring from full-time work was associated with bedtimes that were 30, 31, and 36 min later 1, 2, and 3 y postretirement; wake times that were 63, 69, and 78 min later; and sleep durations that were 15, 16, and 22 min longer 1, 2, and 3 y postretirement. These associations did not differ by sex or mental health status. Age and circadian preference modified the associations between retirement and change in sleep parameters; the increase in sleep duration was shorter and the wake time extension was lesser with advancing retirement age; those with evening preference had longer wake time extensions than those with morning preference. CONCLUSION: Transitioning to retirement is associated with longer sleep duration, later bedtimes, and later wake times. These changes were detectable about 1 y postwork transition and were persistent up to 3 y later. PMID- 26564126 TI - RGS Proteins and Galphai2 Modulate Sleep, Wakefulness, and Disruption of Sleep/ Wake States after Isoflurane and Sevoflurane Anesthesia. AB - STUDY OBJECTIVES: This study tested the hypothesis that Regulators of G protein Signaling (RGS) proteins contribute to the regulation of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to sleep disruption caused by volatile anesthetics. METHODS: The three groups used in this study included wild-type (WT; n = 7) mice and knock-in mice that were heterozygous (+/GS; n = 7) or homozygous (GS/GS; n = 7) for an RGS-insensitive allele that causes prolonged Galphai2 signaling. Mice were implanted with electrodes for recording sleep and conditioned for 1 week or more to sleep in the laboratory. Using within and between groups designs, 24-h recordings of wakefulness, NREM sleep, and REM sleep were compared across three interventions: (1) baseline (control) and after 3 h of being anesthetized with (2) isoflurane or (3) sevoflurane. RESULTS: Baseline recordings during the light phase revealed that relative to WT mice, homozygous RGS-insensitive (GS/GS) mice exhibit significantly increased wakefulness and decreased NREM and REM sleep. During the dark phase, these state-specific differences remained significant but reversed direction of change. After cessation of isoflurane and sevoflurane anesthesia there was a long-lasting and significant disruption of sleep and wakefulness. The durations of average episodes of wakefulness, NREM sleep, and REM sleep were significantly altered as a function of genotype and isoflurane and sevoflurane anesthesia. CONCLUSIONS: RGS proteins and Galphai2 play a significant role in regulating states of wakefulness, NREM sleep, and REM sleep. Genotype-specific differences demonstrate that RGS proteins modulate sleep disruption caused by isoflurane and sevoflurane anesthesia. The results also support the conclusion that isoflurane and sevoflurane anesthesia do not satisfy the homeostatic drive for sleep. PMID- 26564127 TI - Longer Sleep Duration and Midday Napping Are Associated with a Higher Risk of CHD Incidence in Middle-Aged and Older Chinese: the Dongfeng-Tongji Cohort Study. AB - STUDY OBJECTIVES: To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults. METHODS: We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses. RESULTS: Compared with sleeping 7- < 8 h/night, the hazard ratio (HR) of CHD incidence was 1.33 (95% CI = 1.10 to 1.62) for sleeping >= 10 h/night. The association was particularly evident among individuals who were normal weight and without diabetes. Similarly, the HR of incident CHD was 1.25 (95% CI = 1.05 to 1.49) for midday napping > 90 min compared with 1-30 min. When sleep duration and midday napping were combined, individuals having sleep duration >= 10 h and midday napping > 90 min were at a greater risk of CHD than those with sleeping 7- < 8 h and napping 1-30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration >= 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping > 90 min was related to increased waist circumference. CONCLUSIONS: Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships. PMID- 26564128 TI - Impact of Restless Legs Syndrome on Cardiovascular Autonomic Control. AB - STUDY OBJECTIVES: To examine whether patients with restless legs syndrome demonstrate specific alterations in cardiovascular autonomic control. METHODS: Patients with moderate-severe restless legs syndrome (n = 20, 80% female) and controls (n = 20) matched for age, sex, body mass index, and free of hypertension and cardiovascular disease were enrolled. We assessed cardiovagal baroreflex gain via the modified Oxford technique, sympathetically mediated vascular responses to isometric exercise to fatigue, bradycardiac response to Valsalva maneuver, and respiratory sinus arrhythmia during paced breathing. Standard electrocardiography, beat-by-beat arterial pressure, respiration, and popliteal blood flow velocity were recorded continuously. RESULTS: Resting blood pressure and heart rate were similar between groups. However, baroreflex gain averaged 14.3 +/- 1.4 msec/mm Hg in restless legs syndrome and was lower than in controls (22.6 +/- 3.5 msec/mm Hg, P = 0.04). Hemodynamic responses to isometric exercise were similar between groups, though participants with restless legs syndrome had lower leg blood flow (P < 0.001), with greater leg vascular resistance (P < 0.0001), before and during isometric exercise. Respiratory sinus arrhythmia and Valsalva ratios were similar between groups. Neither baroreflex gain nor vascular resistance was correlated with sleep duration, sleep quality, or symptom duration. CONCLUSION: Patients with restless legs syndrome demonstrate compromised cardiovagal control, specific to the arterial baroreflex, with greater peripheral vascular resistance, potentially due to heightened sympathetic outflow. These autonomic alterations may directly relate to the higher prevalence of cardiovascular disease in restless legs syndrome. PMID- 26564129 TI - Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study. AB - STUDY OBJECTIVES: Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. METHODS: We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. RESULTS: An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. CONCLUSIONS: We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans. PMID- 26564130 TI - Expanded Insights into Idiopathic REM Sleep Behavior Disorder. PMID- 26564132 TI - Waking Up to the Importance of Sleep and Circadian Rhythms for Metabolic Health: The Need for In-Depth Phenotyping. PMID- 26564133 TI - Is Sleep Health a Potential Pathway to Global Mental Health? PMID- 26564131 TI - Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions. AB - A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice. PMID- 26564134 TI - CBT-I Cannot Rest Until the Sleepy Teen Can. PMID- 26564135 TI - A Step Forward for Better Interpreting the Apnea-Hypopnea Index. PMID- 26564136 TI - Banking Sleep and Biological Sleep Need. PMID- 26564137 TI - Fragmented Sleep and Cortical Thinning in Old Adults: Time to Wake Up? PMID- 26564138 TI - Locus Coeruleus Neural Fatigue: A Potential Mechanism for Cognitive Impairment during Sleep Deprivation. PMID- 26564139 TI - Sleep, Sleep Alterations, Stress--Combined Effects on Memory? PMID- 26564140 TI - The Promise of Digital CBT-I. PMID- 26564141 TI - Memantine and Kynurenic Acid: Current Neuropharmacological Aspects. AB - Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive activation of N-methyl- D-aspartate (NMDA) receptors may result in excitotoxic neuronal damage; this process has been implicated in the pathomechanism of different neurodegenerative disorders, such as Alzheimer's disease (AD). Memantine is an uncompetitive antagonist of NMDA receptors with a favorable pharmacokinetic profile, and is therefore clinically well tolerated. Memantine is approved for the treatment of AD, but may additionally be beneficial for other dementia forms and pain conditions. Kynurenic acid (KYNA) is an endogenous antagonist of NMDA receptors which has been demonstrated under experimental conditions to be neuroprotective. The development of a well tolerated NMDA antagonist may offer a novel therapeutic option for the treatment of neurodegenerative disease and pain syndromes. KYNA may be a valuable candidate for future drug development. PMID- 26564142 TI - Mappability of drug-like space: towards a polypharmacologically competent map of drug-relevant compounds. AB - Intuitive, visual rendering--mapping--of high-dimensional chemical spaces (CS), is an important topic in chemoinformatics. Such maps were so far dedicated to specific compound collections--either limited series of known activities, or large, even exhaustive enumerations of molecules, but without associated property data. Typically, they were challenged to answer some classification problem with respect to those same molecules, admired for their aesthetical virtues and then forgotten--because they were set-specific constructs. This work wishes to address the question whether a general, compound set-independent map can be generated, and the claim of "universality" quantitatively justified, with respect to all the structure-activity information available so far--or, more realistically, an exploitable but significant fraction thereof. The "universal" CS map is expected to project molecules from the initial CS into a lower-dimensional space that is neighborhood behavior-compliant with respect to a large panel of ligand properties. Such map should be able to discriminate actives from inactives, or even support quantitative neighborhood-based, parameter-free property prediction (regression) models, for a wide panel of targets and target families. It should be polypharmacologically competent, without requiring any target-specific parameter fitting. This work describes an evolutionary growth procedure of such maps, based on generative topographic mapping, followed by the validation of their polypharmacological competence. Validation was achieved with respect to a maximum of exploitable structure-activity information, covering all of Homo sapiens proteins of the ChEMBL database, antiparasitic and antiviral data, etc. Five evolved maps satisfactorily solved hundreds of activity-based ligand classification challenges for targets, and even in vivo properties independent from training data. They also stood chemogenomics-related challenges, as cumulated responsibility vectors obtained by mapping of target-specific ligand collections were shown to represent validated target descriptors, complying with currently accepted target classification in biology. Therefore, they represent, in our opinion, a robust and well documented answer to the key question "What is a good CS map?" PMID- 26564143 TI - Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation. AB - Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A). In these studies, the binding of macrolide antibiotic Ery to wild type (Wt) MphR(A) and double mutant (V66L/V126L) MphR(A) are explored by molecular dynamics simulations. Compared to the Apo-MphR(A) protein and Wt MphR(A)-Ery complex, many interesting effects owing to the double mutant (V66L/V126L) are discovered. In the case of Ery, Helix I which plays an important role in transcription shows itself a right-hand alpha helix in Wt-MphR(A)-Ery, whereas the activated helix is broken down in double mutant-V66L/V126L-MphR(A) Ery. The calculated results exhibit that the double mutant V66L/V126L reduces the binding affinity of the V66L/V126L-MphR(A) to Ery, resulting in the block of Ery resistance. The binding free energy decomposition analysis reveals that the decrease of the binding affinity for the variant V66L/V126L-MphR(A)-Ery is mainly attributed to the gas phase electrostatic energies. The residue Leu66, Thr154, and Arg122 enhance the binding affinity of V66L/V126L-MphR(A) to Ery. The residues Tyr103 and His147 contributes mainly to binding energies in the Wt MphR(A)-Ery complex, whereas the two residues have no contribution to the binding free energy inV66L/V126L-MphR(A)-Ery complex. Our study gives useful insights into the nature of amino acids mutation effect, the mechanism of blocking drug resistance at the atomic level and the characteristics in binding affinity for Ery to double mutant (V66L/V126L) MphR(A), which will contribute to the design of more effective macrolide antibiotics. PMID- 26564144 TI - The developing paradigm of urologic training in the USA. PMID- 26564145 TI - Tripterysium glycosides preconditioning attenuates renal ischemia/reperfusion injury in a rat model. AB - BACKGROUND: Ischemia-reperfusion (I/R) injury to the kidney occurs commonly in organ transplantation from donation after cardiac death, involving many pathologic processes. In this study, we used rat model to assess whether tripterysium glycosides (TG) preconditioning could exert protective effects in renal I/R injury. MATERIALS AND METHODS: All male SD rats were randomly divided into four groups (6 each): sham group, TG group, I/R group and TG + I/R group. Groups TG and TG + I/R were pretreated with TG at 0.1 mg/kg for 14 days; groups sham and I/R were administered with the same dosage of normal saline. Groups TG + I/R and I/R underwent 45 min of renal ischemia of left kidney after right nephrectomy, and then, they were subjected to 72-h reperfusion. Groups sham and TG were only received right nephrectomy. The indicators of apoptosis, fibrosis and inflammation were analyzed to evaluate the effect of tripterysium glycosides preconditioning on renal I/R injury. RESULTS: Pretreatment with TG significantly inhibited the levels of serum creatine and blood urea nitrogen and improved histologic lesions induced by I/R injury. Moreover, for the apoptosis signal pathway, pretreatment with TG markedly decreased the expression of caspase-3 and Bax and increased the level of Bcl-2. HMGB1, which was regarded as one of inflammation marker molecule, it was inhibited in the TG + I/R group. For the fibrosis signal pathway, the pretreatment with TG before I/R could down-regulate the expression level of typical molecules of fibrosis (TGF-beta1, Smad3, p Smad3). CONCLUSIONS: Pretreatment with tripterysium glycosides exhibited protective effect on kidney ischemia/reperfusion injury, which might be related to the alleviation of inflammation, fibrosis and the reduction in apoptosis. PMID- 26564146 TI - Product rotational angular momentum polarization of H+FCl (v=0-5; j=0, 3, 6, 9) > HF+Cl and HCl+F at Erel=0.5-20 kcal mol(-1). AB - The rotational angular momentum polarizations of product molecules of the title reactions on the ground potential energy surface 1 (2)A' of DHTSN [Deskevic et al. J Chem Phys 2006, 124, 224303] have been studied using the quasi-classical trajectory method. Reaction dynamic results of the HF product channel comparing with another channel of HCl with 100,000 trajectories can be accurately resolved. We show the value of the polar p(thetar) in the range of 0 degrees <= thetar <= 180( degrees ), azimuthal p(phir) in the range of 0 degrees <= phir <= 360( degrees ), and dihedral p(thetar, phir) in the ranges of 0( degrees ) <= thetar <= 180( degrees ) and 0( degrees ) <= phir <= 360( degrees ); the angular distributions of the product molecules HF and HCl at relative Erel = 0.5, 1, 2, 5, 10, 15, and 20 kcal mol(-1); and four polarization-dependent differential cross sections (PDDCSs) of HF and HCl at Erel = 0.5, 1, 2, 5, 10, and 15 kcal mol(-1). p(phir) distributions at v = 0-5, and j = 0, 3, 6, 9 at every Erel are plotted cylindrically together. The stereo dynamic transformation reaction dependent upon the rovibrational states of the reactant molecule FCl and its relative translational energies around 0.5-5 kcal mol(-1) can be significantly differentiated. Translational and rovibrational enhancements of the title reactions on both early barrier potential energy surfaces have been shown in great detail and clarified. Reaction mechanisms of forward and backward scattering of the product molecules HF and HCl, respectively, have been obtained. Graphical Abstract H + FCl -> either HF + Cl (left) or HCl + F (right) is moving along a trajectory on the respective PES. PMID- 26564147 TI - Functional insights from a comparative study on the dynamics of Antigen85 proteins and MPT51 from Mycobacterium tuberculosis. AB - Antigen85 (Ag85) proteins of Mycobacterium tuberculosis are mycolyl transferases that aid in cell wall biosynthesis. MPT51 (Ag85D) is closely related to Ag85 proteins. We have performed a comparative molecular dynamics (MD) simulation study of Ag85 proteins (Ag85A, Ag85B, and Ag85C) and MPT51. We observe that helix alpha5, beta7-alpha9 loop, and N-terminal region of helix alpha9 of Ag85 proteins are mobile, suggestive of lid like movement over the active site. Further, in Ag85B, we observe the proposed scooting mode of the hydrophobic gating residue Phe232. Our simulations also show a similar scooting mode for Phe232 of Ag85A and Trp158 of Ag85C. We also found aromatic residue clusters at the ends of the hydrophobic channel of Ag85 proteins, which may have functional significance. Although MPT51 lacks the tunnel, it has the aromatic clusters. The aromatic cluster region has the ability to bind trehalose. From an immunoinformatics study, a promiscuous linear epitope was identified in MPT51 which could be useful in subunit vaccine studies. Recent studies have shown that a mycobacterial protein HupB, interacts with Ag85 proteins and has a regulatory role in cell wall biogenesis, with implications in growth rate and latency. We performed molecular docking studies of HupB protein with Ag85 proteins and predicted potential sites of interaction in Ag85 proteins. The insights gained through the current study can potentially pave way for newer therapeutic interventions. Graphical Abstract Dynamics of antigen85 proteins and MPT51 from Mycobacterium tuberculosis. PMID- 26564148 TI - Management strategy for bilateral complex vertebral artery aneurysms. AB - Bilateral complex vertebral artery aneurysms (BCoVAAns) have no established strategy of management. We retrospectively reviewed five consecutive patients with unruptured BCoVAAns between January 2006 and December 2012. Considering surgical risks of lower cranial nerve (LCN) injuries and eventual growth of an opposite side lesion after unilateral vertebral artery (VA) occlusion, we proposed a strategy of combined open and interventional treatment using revascularization. We applied the following several specific techniques: (1) proximal clipping and occipital artery-posterior inferior cerebellar artery (OA PICA) and/or superficial temporary artery (STA)-superior cerebellar artery (SCA) bypasses; (2) Distal blood pressure, motor evoked potentials (MEPs), and somatosensory evoked potentials (SEPs) monitoring after parent artery temporary occlusion for safe permanent occlusion of the proximal portions of VA and PICA; (3) V3 to V4 bypass using radial artery (RA) graft with proximal clipping or trapping, two of them combined with OA-PICA bypass; (4) VA fenestration as an opportunity to preserve the flow of the parent artery. Two patients were treated bilaterally and 3 unilaterally, with modified Rankin scale assessed at 39 months postoperatively in average 0 in 2, 1 in 2, and 2 in 1, respectively, and the untreated opposite side lesions without regrowth or bleeding. Two patients with patent V3-RA-V4 bypass complained of dysphagia due to LCN palsies. One of them however suffered a cerebellar infarction due to occlusion of the OA-PICA bypass. When BCoVAAns require surgical treatment, revascularization or preservation of the VA should be considered at the first operation. By doing so, the opposite aneurysm can be effectively occluded by coil embolization, even with VA sacrifice if required. PMID- 26564149 TI - Difference of language cortex reorganization between cerebral arteriovenous malformations, cavernous malformations, and gliomas: a functional MRI study. AB - The authors attempted to demonstrate the difference in language cortex reorganization between cerebral malformations (AVMs), cavernous malformations (CMs), and gliomas by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Clinical and imaging data of 27 AVM patients (AVM-L group), 29 CM patients (CM-L group), and 20 glioma patients (Glioma-L group) were retrospectively reviewed, with lesions overlying the left inferior frontal gyrus (Broca area). As a control, patients with lesions involving the right inferior frontal gyrus were also enrolled, including 14 AVM patients (AVM-R group), 20 CM patients (CM-R group), and 14 glioma patients (Glioma-R group). All patients were right-handed. Lateralization indices (LI) of BOLD signal activations were calculated separately for Broca and Wernicke areas. In AVM-L group, right-sided lateralization of BOLD signals was observed in 10 patients (37.0%), including 6 in the Broca area alone, 1 in the Wernicke area alone, and 3 in both areas. Three patients (10.3%) of CM-L group showed right-sided lateralization in both Broca and Wernicke areas, and 1 patient (5.0%) of Glioma-L group had right-sided lateralization in the Wernicke area alone. A significant difference of right sided lateralization was observed between the AVM-L group and CM-L group (P = 0.018) and also between the AVM-L group and Glioma-L group (P = 0.027). No patient in AVM-R, CM-R, or Glioma-R groups showed right-sided lateralization. Language cortex reorganization may occur in AVM, CM, and glioma patients when the traditional language cortex was involved by lesions, but the potential of reorganization for CM and glioma patients seems to be insufficient compared with AVM patients. PMID- 26564150 TI - Syringomatous adenoma of the nipple: a case report. AB - INTRODUCTION: Syringomatous adenoma of the nipple is a very rare benign tumor. To the best of our knowledge, there are no reports of a syringomatous adenoma of the nipple metastasizing, although these tumors are known to infiltrate locally and to recur if not totally resected. CASE PRESENTATION: Our patient was a 41-year old Japanese woman who complained of stiffness of her right nipple with abnormal discharge. Local resection of the tumor was performed. The pathological diagnosis was syringomatous adenoma of the nipple, and the resection margin was found to be positive. Accordingly, additional resection was recommended, but our patient did not allow another operation. After 1.5 years of careful follow-up, no local recurrence or distant metastasis has been observed. CONCLUSION: The optimal initial management of syringomatous adenoma of the nipple demands complete resection with histologically negative margins. However, from a cosmetic viewpoint, nipple-sparing resection could represent an alternative option for the treatment of syringomatous adenoma of the nipple. PMID- 26564151 TI - The thyroid status reprograms T cell lymphoma growth and modulates immune cell frequencies. AB - In spite of considerable evidence on the regulation of immunity by thyroid hormones, the impact of the thyroid status in tumor immunity is poorly understood. Here, we evaluated the antitumor immune responses evoked in mice with different thyroid status (euthyroid, hyperthyroid, and hypothyroid) that developed solid tumors or metastases after inoculation of syngeneic T lymphoma cells. Hyperthyroid mice showed increased tumor growth along with increased expression of cell cycle regulators compared to hypothyroid and control tumor bearing mice. However, hypothyroid mice showed a higher frequency of metastases than the other groups. Hyperthyroid mice bearing tumors displayed a lower number of tumor-infiltrating T lymphocytes, lower percentage of functional IFN-gamma producing CD8(+) T cells, and higher percentage of CD19(+) B cells than euthyroid tumor-bearing mice. However, no differences were found in the distribution of lymphocyte subpopulations in tumor-draining lymph nodes (TDLNs) or spleens among different experimental groups. Interestingly, hypothyroid TDLN showed an increased percentage of regulatory T (Treg) cells, while hyperthyroid mice displayed increased number and activity of splenic NK cells, which frequency declined in spleens from hypothyroid mice. Moreover, a decreased number of splenic myeloid-derived suppressor cells (MDSCs) were found in tumor-bearing hyperthyroid mice as compared to hypothyroid or euthyroid mice. Additionally, hyperthyroid mice showed increased cytotoxic activity, which declined in hypothyroid mice. Thus, low levels of intratumoral cytotoxic activity would favor tumor local growth in hyperthyroid mice, while regional and systemic antitumor response may contribute to tumor dissemination in hypothyroid animals. Our results highlight the importance of monitoring the thyroid status in patients with T cell lymphomas. KEY MESSAGES: T cell lymphoma phenotype is paradoxically influenced by thyroid status. Hyperthyroidism favors tumor growth and hypothyroidism rises tumor dissemination. Thyroid status affects the distribution of immune cell types in the tumor milieu. Thyroid status also modifies the nature of local and systemic immune responses. PMID- 26564152 TI - The RING Finger Ubiquitin E3 Ligase OsHTAS Enhances Heat Tolerance by Promoting H2O2-Induced Stomatal Closure in Rice. AB - Heat stress often results in the generation of reactive oxygen species, such as hydrogen peroxide, which plays a vital role as a secondary messenger in the process of abscisic acid (ABA)-mediated stomatal closure. Here, we characterized the rice (Oryza sativa) HEAT TOLERANCE AT SEEDLING STAGE (OsHTAS) gene, which plays a positive role in heat tolerance at the seedling stage. OsHTAS encodes a ubiquitin ligase localized to the nucleus and cytoplasm. OsHTAS expression was detected in all tissues surveyed and peaked in leaf blade, in which the expression was concentrated in mesophyll cells. OsHTAS was responsive to multiple stresses and was strongly induced by exogenous ABA. In yeast two-hybrid assays, OsHTAS interacted with components of the ubiquitin/26S proteasome system and an isoform of rice ascorbate peroxidase. OsHTAS modulated hydrogen peroxide accumulation in shoots, altered the stomatal aperture status of rice leaves, and promoted ABA biosynthesis. The results suggested that the RING finger ubiquitin E3 ligase OsHTAS functions in leaf blade to enhance heat tolerance through modulation of hydrogen peroxide-induced stomatal closure and is involved in both ABA-dependent and DROUGHT AND SALT TOLERANCE-mediated pathways. PMID- 26564153 TI - Quinoline-Based Compound BPIQ Exerts Anti-Proliferative Effects on Human Retinoblastoma Cells via Modulating Intracellular Reactive Oxygen Species. AB - Retinoblastoma (Rb) is the most common primary intraocular malignant tumor of childhood. It is important to develop the strategy for Rb treatment. We have tested a quinolone derivative 2,9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2 (pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) for its anti-cancer effects against Rb via cultured human Rb cell line Y79. Our results showed that BPIQ significantly inhibits cell growth of Y79. Furthermore, the flow cytometer-based assays and Western blotting showed that BPIQ induces the apoptosis of Y79 via increasing the level of reactive oxygen species (ROS). Besides, the activation of gammaH2AX, a DNA damage sensor in human Y79 cells was also observed, indicating the potential of BPIQ for causing DNA damage of Rb cells. On the contrary, BPIQ-induced apoptosis of Y79 cells was attenuated significantly by N-acetyl-L-cysteine (NAC), an ROS scavenger. The results of Western blot showed that BPIQ down-regulates the levels of anti-apoptotic proteins Bcl-2, survivin and XIAP while up-regulates the pro-apoptotic proteins Bad, Bax and Bid. Our present study demonstrated the anti-proliferative effect of BPIQ in human Y79 cells. The inhibitory effect of BPIQ on the proliferation of Y79 cells is, at least, partly mediated by the regulation of ROS and DNA damage pathway. In conclusion, BPIQ may provide an alternative option in the chemotherapeutics or chemoprevention on the Rb therapy in the future. PMID- 26564156 TI - Editorial: Nanotechnology for Drug Delivery: Part III. PMID- 26564154 TI - Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention. AB - Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway. PMID- 26564155 TI - The effect of renin-angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy. AB - BACKGROUND: The impact of renin-angiotensin system blockade (RASB) on the incidence of end-stage renal disease (ESRD) remains unclear in IgA nephropathy (IgAN). METHODS: This study assessed associations between RASB treatment and the incidence of ESRD in IgAN using propensity score approaches. We retrospectively analyzed 1273 patients with IgAN biopsied between 1979 and 2010. Propensity scores were calculated using logistic regression. Associations between RASB and ESRD were examined using a Cox regression model adjusted by inverse probability of treatment weighted, regression, stratification and matching. RESULTS: During follow-up (median 5.1 years), 130 patients developed ESRD. With Cox regression adjusted by inverse probability of treatment weighted, RASB use was significantly associated with a lower risk of ESRD (hazard ratio 0.58; 95 % confidence interval 0.42-0.80). Significant associations were observed for other propensity score based approaches. In stratified analysis, a beneficial association between RASB and ESRD was observed in patients >=35 years, with hypertension, reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2), mesangial proliferation and segmental glomerulosclerosis (P for interaction <0.05), and tended to be greater in patients with proteinuria (>=1.0 g/24 h), extracapillary proliferation and receiving methylprednisolone pulse therapy (P for interaction <0.10). CONCLUSION: Treatment with RASB was associated with a lower incidence of ESRD in the real-world practice of IgAN. PMID- 26564157 TI - Combined Interactions of Plant Homeodomain and Chromodomain Regulate NuA4 Activity at DNA Double-Strand Breaks. AB - DNA double-strand breaks (DSBs) represent one of the most threatening lesions to the integrity of genomes. In yeast Saccharomyces cerevisiae, NuA4, a histone acetylation complex, is recruited to DSBs, wherein it acetylates histones H2A and H4, presumably relaxing the chromatin and allowing access to repair proteins. Two subunits of NuA4, Yng2 and Eaf3, can interact in vitro with methylated H3K4 and H3K36 via their plant homeodomain (PHD) and chromodomain. However, the roles of the two domains and how they interact in a combinatorial fashion are still poorly characterized. In this study, we generated mutations in the PHD and chromodomain that disrupt their interaction with methylated H3K4 and H3K36. We demonstrate that the combined mutations in both the PHD and chromodomain impair the NuA4 recruitment, reduce H4K12 acetylation at the DSB site, and confer sensitivity to bleomycin that induces DSBs. In addition, the double mutant cells are defective in DSB repair as judged by Southern blot and exhibit prolonged activation of phospho-S129 of H2A. Cells harboring the H3K4R, H3K4R, K36R, or set1Delta set2Delta mutant that disrupts H3K4 and H3K36 methylation also show very similar phenotypes to the PHD and chromodomain double mutant. Our results suggest that multivalent interactions between the PHD, chromodomain, and methylated H3K4 and H3K36 act in a combinatorial manner to recruit NuA4 and regulate the NuA4 activity at the DSB site. PMID- 26564159 TI - Synergistic Pleiotropy Overrides the Costs of Complexity in Viral Adaptation. AB - Adaptive evolution progresses as a series of steps toward a multidimensional phenotypic optimum, and organismal or environmental complexity determines the number of phenotypic dimensions, or traits, under selection. Populations evolving in complex environments may experience costs of complexity such that improvement in one or more traits is impeded by selection on others. We compared the fitness effects of the first fixed mutations for populations of single-stranded DNA bacteriophage evolving under simple selection for growth rate to those of populations evolving under more complex selection for growth rate as well as capsid stability. We detected a cost of complexity manifested as a smaller growth rate improvement for mutations fixed under complex conditions. We found that, despite imposing a cost for growth rate improvement, strong complex selection resulted in the greatest overall fitness improvement, even for single mutations. Under weaker secondary selective pressures, tradeoffs between growth rate and stability were pervasive, but strong selection on the secondary trait resulted largely in mutations beneficial to both traits. Strength of selection therefore determined the nature of pleiotropy governing observed trait evolution, and strong positive selection forced populations to find mutations that improved multiple traits, thereby overriding costs incurred as a result of a more complex selective environment. The costs of complexity, however, remained substantial when considering the effects on a single trait in the context of selection on multiple traits. PMID- 26564161 TI - [Not Available]. PMID- 26564158 TI - Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins in Drosophila Oocytes. AB - Oocytes segregate chromosomes in the absence of centrosomes. In this situation, the chromosomes direct spindle assembly. It is still unclear in this system which factors are required for homologous chromosome bi-orientation and spindle assembly. The Drosophila kinesin-6 protein Subito, although nonessential for mitotic spindle assembly, is required to organize a bipolar meiotic spindle and chromosome bi-orientation in oocytes. Along with the chromosomal passenger complex (CPC), Subito is an important part of the metaphase I central spindle. In this study we have conducted genetic screens to identify genes that interact with subito or the CPC component Incenp. In addition, the meiotic mutant phenotype for some of the genes identified in these screens were characterized. We show, in part through the use of a heat-shock-inducible system, that the Centralspindlin component RacGAP50C and downstream regulators of cytokinesis Rho1, Sticky, and RhoGEF2 are required for homologous chromosome bi-orientation in metaphase I oocytes. This suggests a novel function for proteins normally involved in mitotic cell division in the regulation of microtubule-chromosome interactions. We also show that the kinetochore protein, Polo kinase, is required for maintaining chromosome alignment and spindle organization in metaphase I oocytes. In combination our results support a model where the meiotic central spindle and associated proteins are essential for acentrosomal chromosome segregation. PMID- 26564160 TI - Genomic Analyses of Sperm Fate Regulator Targets Reveal a Common Set of Oogenic mRNAs in Caenorhabditis elegans. AB - Germ cell specification as sperm or oocyte is an ancient cell fate decision, but its molecular regulation is poorly understood. In Caenorhabditis elegans, the FOG 1 and FOG-3 proteins behave genetically as terminal regulators of sperm fate specification. Both are homologous to well-established RNA regulators, suggesting that FOG-1 and FOG-3 specify the sperm fate post-transcriptionally. We predicted that FOG-1 and FOG-3, as terminal regulators of the sperm fate, might regulate a battery of gamete-specific differentiation genes. Here we test that prediction by exploring on a genomic scale the messenger RNAs (mRNAs) associated with FOG-1 and FOG-3. Immunoprecipitation of the proteins and their associated mRNAs from spermatogenic germlines identifies 81 FOG-1 and 722 FOG-3 putative targets. Importantly, almost all FOG-1 targets are also FOG-3 targets, and these common targets are strongly biased for oogenic mRNAs. The discovery of common target mRNAs suggested that FOG-1 and FOG-3 work together. Consistent with that idea, we find that FOG-1 and FOG-3 proteins co-immunoprecipitate from both intact nematodes and mammalian tissue culture cells and that they colocalize in germ cells. Taking our results together, we propose a model in which FOG-1 and FOG-3 work in a complex to repress oogenic transcripts and thereby promote the sperm fate. PMID- 26564162 TI - Electronic cigarette use among Korean adults. AB - OBJECTIVES: We investigated the prevalence and correlates of electronic cigarette (e-cigarette) use in a representative sample of Korean adults. METHODS: This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey of 2013. We analyzed 5338 subjects (>=19 years old) who provided data on e-cigarette use, sex, age, socioeconomic status, and health risk behaviors. Multivariate analyses were performed using logistic regression. RESULTS: Using weighted samples, the prevalence of ever and current e-cigarette use were 6.6 and 1.1 %, respectively (11.2 and 2.0 % in men and 2.0 and 0.4 % in women). In multivariate analysis, the probability of ever e-cigarette use was highest in current smokers (OR 29.3, 95 % CI 15.5-55.3), former smokers (OR 6.1, 95 % CI 3.3-11.2), and daily heavy drinkers (OR 1.9, 95 % CI 1.1-3.4). Current e cigarette use was associated with current smoking (OR 16.2, 95 % CI 4.7-55.4) and weekly heavy drinking (OR 2.7, 95 % CI 1.1-6.7). CONCLUSIONS: E-cigarette use was strongly associated with conventional cigarette use and with frequent heavy drinking. Dual use e-cigarettes and conventional cigarette use as well as the association between heavy alcohol use and e-cigarettes need further exploration. PMID- 26564163 TI - Injuries can prolong lifespan in Drosophila melanogaster males. AB - Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected to one of five treatments ranging from control, over perforating the cuticle with a sterile needle, to inoculating with peptidoglycan or one of two strains of live bacteria. The flies were subjected to the infection stress at two ages and the experiment was conducted on both males and females of replicate lines of each selection regime. The individual lines and sexes differed in response to the treatment. However, overall the sterile injury of young males resulted in prolonged mean lifespan from both selection regimes, whereas inoculating had no additional effect to stabbing with a sterile needle. In middle-aged males only treatment with peptidoglycan had a significant hormetic effect and this was only in longevity-selected flies. In females only one of the tested contrasts was significant and here the effect of the treatment was to reduce average lifespan. As could be expected, the results showed a significant interaction between the effects of sex and infection on survival. PMID- 26564164 TI - Does smoke cross the border? Cigarette tax avoidance in France. AB - This paper examines the impact on cigarette sales of the successive increases in cigarette prices in France from 2002 to 2004. Since the price differential between France and neighboring countries increased over the period in question, cross-border purchases became more financially attractive for smokers living near borders. Results from difference-in-differences estimates indicate that the decrease in cigarette sales observed in French border departments was around 20 % higher from 2004 to 2007 compared to non-border departments. The loss of fiscal revenue due to cross-border shopping since the tax increase amounts to 2 billion euros over the period 2002-2007. Our findings highlight the need for improved coordination of policies aimed at reducing tobacco consumption across European Union countries. PMID- 26564166 TI - Penciling in details of the Hadean. PMID- 26564165 TI - Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions. AB - INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) are considered as one of the most promising seed cell sources in regenerative medicine. Now hiPSC-based clinical trials are underway. To ensure clinical safety, cells used in clinical trials or therapies should be generated under GMP conditions, and with Xeno-free culture media to avoid possible side effects like immune rejection that induced by the Xeno reagents. However, up to now there are no reports for hiPSC lines developed completely under GMP conditions using Xeno-free reagents. METHODS: Clinical-grade human foreskin fibroblast (HFF) cells used as feeder cells and parental cells of the clinical-grade hiPSCs were isolated from human foreskin tissues and cultured in Xeno-free media. Clinical-grade hiPSCs were derived by integration-free Sendai virus-based reprogramming kit in Xeno-free pluritonTM reprogramming medium or X medium. Neural cells and cardiomyocytes differentiation were conducted following a series of spatial and temporal specific signals induction according to the corresponding lineage development signals. Biological safety evaluation of the clinical-grade HFF cells and hiPSCs were conducted following the guidance of the "Pharmacopoeia of the People's Republic of China, Edition 2010, Volume III". RESULTS: We have successfully derived several integration-free clinical-grade hiPSC lines under GMP-controlled conditions and with Xeno-free reagents culture media in line with the current guidance of international and national evaluation criteria. As for the source of hiPSCs and feeder cells, biological safety evaluation of the HFF cells have been strictly reviewed by the National Institutes for Food and Drug Control (NIFDC). The hiPSC lines are pluripotent and have passed the safety evaluation. Moreover, one of the randomly selected hiPSC lines was capable of differentiating into functional neural cells and cardiomyocytes in Xeno-free culture media. CONCLUSION: The clinical-grade hiPSC lines therefore could be valuable sources for future hiPSC based clinical trials or therapies and for drug screening. PMID- 26564167 TI - Costs and benefits of group living are neither simple nor linear. PMID- 26564168 TI - Weak association between sleep bruxism and obstructive sleep apnea. A sleep laboratory study. AB - PURPOSE: No definitive associations or causal relationships have been determined between obstructive sleep apnea-hypopnea (OSAH) and sleep bruxism (SB). The purpose of this study was to investigate, in a population reporting awareness of both OSAH and SB, the associations between each specific breathing and jaw muscle event. METHODS: Polysomnography and audio-video data of 59 patients reporting concomitant OSAH and SB history were analyzed. Masseteric bursts after sleep onset were scored and classified into three categories: (1) sleep rhythmic masticatory muscle activity with SB (RMMA/SB), (2) sleep oromotor activity other than RMMA/SB (Sleep-OMA), and (3) wake oromotor activity after sleep onset (Wake OMA). Spearman's rank correlation coefficient analyses were performed. Dependent variables were the number of RMMA/SB episodes, RMMA/SB bursts, Sleep-OMA, and Wake-OMA; independent variables were apnea-hypopnea index (AHI), arousal index(AI), body mass index(BMI), gender, and age. RESULTS: Although all subjects had a history of both SB and OSAH, sleep laboratory results confirmed that these conditions were concomitant in only 50.8 % of subjects. Moderate correlations were found in the following combinations (p < 0.05); RMMA/SB episode with AI, RMMA/SB burst with AI and age, Sleep-OMA burst with AHI, and Wake-OMA burst with BMI. CONCLUSIONS: The results suggest that (1) sleep arousals in patients with concomitant SB and OSAH are not strongly associated with onset of RMMA/SB and (2) apnea-hypopnea events appear to be related to higher occurrence of other types of sleep oromotor activity, and not SB activity. SB genesis and OSAH activity during sleep are probably influenced by different mechanisms. PMID- 26564169 TI - Impaired sustained attention and lapses are present in patients with mild obstructive sleep apnea. AB - BACKGROUND: Severe obstructive sleep apnea (OSA) directly affects the quality of life, mood, and sustained attention of individuals, but it has not yet been established in the literature, if these changes also affect patients with mild OSA. The purpose of this study was to investigate such negative effects on the parameters described above. METHODS: A controlled study was held at the Universidade Federal de Sao Paulo, Department of Psychobiology. Thirty-nine mild OSA patients and 25 controls were included. Volunteers could be of both genders with body mass index (BMI) <=35 kg/m(2) and age between 18 and 65 years. Both groups were subjected to full-night polysomnography (PSG), the subjective assessment of mood (Beck Inventory of Anxiety and Depression), Functional Outcomes of Sleep Questionnaire (FOSQ), and the psychomotor vigilance task (PVT) five times during the day. We considered mild OSA patients those with apnea hypopnea index (AHI) score between 5 and 15. The control group included subjects with AHI scores <5, respiratory disturbance index (RDI) scores <=5, arousal index values <=15, and Epworth Sleepiness Scale (ESS) values <=9. RESULTS: Mild OSA patients were older and more obese than the controls. After adjusting for age, BMI, and schooling years, there was an increased number of total lapses (3.90 +/- 4.16 and 2.43 +/- 5.55, p = 0.004). CONCLUSIONS: Patients with mild OSA showed increased sustained attention lapses compared with normal subjects. PMID- 26564170 TI - Use of the sleep clinical record in the follow-up of children with obstructive sleep apnea (OSA) after treatment. AB - PURPOSE: The aim of our study was to evaluate the utility of the sleep clinical record (SCR) in the follow-up of children with obstructive sleep apnea (OSA) after treatment. METHODS: SCR was completed and overnight polysomnography (PSG) was performed in all enrolled children (T0), with SCR considered positive for scores >=6.5, as previously validated. Patients underwent adenotonsillectomy (T&A), rapid maxillary expansion (RME), and medical therapy according to severity of OSA and clinical features. Six months after completing therapy, the second overnight PSG and SCR (T1) were performed. RESULTS: For all subjects, both Apnea Hypopnea Index (AHI) and total SCR score decreased significantly (<0.005) from T0 to T1. For SCR items, clinical examination (item 1) and reported sleep respiratory symptoms (item 2) ameliorated significantly (<0.005). However, hyperactivity or inattention (item 3) decreased significantly (<0.005) after treatment only in T&A group, while no differences in AHI and SCR scores occurred in the medically treated group. At T1, SCR was positive in 95.6 % of children with AHI >=1, with a concordance of 100 % in the T&A and RME groups, resulting in a positive predictive value of 100 %. A poor concordance (38.3 % in T&A group and 53.4 % in RME group) was found when SCR < 6.5. Children with SCR >= 6.5 at T1 showed higher AHI compared to patients with SCR < 6.5 (5.7 +/- 5.9 ev/h vs 1.78 +/- 1.76 ev/h; p < 0.005). CONCLUSIONS: SCR emerges as a potentially useful instrument for follow-up of children with OSA after treatment. PMID- 26564172 TI - Free vibration analysis of microtubules based on the molecular mechanics and continuum beam theory. AB - A molecular structural mechanics (MSM) method has been implemented to investigate the free vibration of microtubules (MTs). The emphasis is placed on the effects of the configuration and the imperfect boundaries of MTs. It is shown that the influence of protofilament number on the fundamental frequency is strong, while the effect of helix-start number is almost negligible. The fundamental frequency is also found to decrease as the number of the blocked filaments at boundaries decreases. Subsequently, the Euler-Bernoulli beam theory is employed to reveal the physics behind the simulation results. Fitting the Euler-Bernoulli beam into the MSM data leads to an explicit formula for the fundamental frequency of MTs with various configurations and identifies a possible correlation between the imperfect boundary conditions and the length-dependent bending stiffness of MTs reported in experiments. PMID- 26564171 TI - Roles of interleukin (IL)-6 gene polymorphisms, serum IL-6 levels, and treatment in obstructive sleep apnea: a meta-analysis. AB - BACKGROUND: Inconsistent results regarding the relationship between interleukin (IL)-6 gene polymorphisms, serum IL-6 levels, and the treatment in obstructive sleep apnea (OSA) have been reported. This meta-analysis assessed the associations between IL-6 gene polymorphisms and OSA susceptibility, IL-6 levels in OSA, and CPAP (continuous positive airway pressure) and T&A (tonsillectomy and adenoidectomy) therapy for IL-6 in OSA. METHODS: Studies regarding IL-6 polymorphisms, serum IL-6 levels, and OSA treatment were identified using PubMed and Embase. The associations between IL-6 gene polymorphisms and OSA risk (estimated by pooling odds ratios (ORs) with 95 % confidence intervals (CIs)) were assessed using an allele model. The pooled standardized mean differences (SMDs) with 95 % CI of IL-6 were estimated using a random-effects model. Meta regression, sensitivity analysis, and publication bias were also evaluated. RESULTS: In total, 53 studies were included. In adults, a significant association between -174 G/C and OSA susceptibility was observed (OR = 1.46, 95 % CI = 1.14 1.87) and IL-6 levels were higher in OSA compared to controls (SMD = 1.56, 95 % CI = 1.18-1.95); however, no association was observed for the -572 G/C allele (OR = 1.13, 95 % CI = 0.87-1.47) and OSA susceptibility and there was no significant change in IL-6 in pre- and post-CPAP therapy (SMD = -0.24, 95 % CI = -0.73 to 0.26). In children, IL-6 levels were also higher in OSA (SMD = 1.27, 95 % CI = 0.29-2.26) and T&A treatment significantly decreased them (SMD = -0.97, 95 % CI = -1.72 to -0.22). CONCLUSIONS: This meta-analysis indicates that the IL-6 gene polymorphism -174 G/C, and not -572 G/C, is associated with adult OSA risk. Although IL-6 levels increased in OSA, CPAP did not significantly suppress them in adults with OSA. In children with OSA, IL-6 levels also increased and T&A therapy significantly decreased them. PMID- 26564173 TI - Multiscale modelling of solid tumour growth: the effect of collagen micromechanics. AB - Here we introduce a model of solid tumour growth coupled with a multiscale biomechanical description of the tumour microenvironment, which facilitates the explicit simulation of fibre-fibre and tumour-fibre interactions. We hypothesise that such a model, which provides a purely mechanical description of tumour-host interactions, can be used to explain experimental observations of the effect of collagen micromechanics on solid tumour growth. The model was specified to mouse tumour data, and numerical simulations were performed. The multiscale model produced lower stresses than an equivalent continuum-like approach, due to a more realistic remodelling of the collagen microstructure. Furthermore, solid tumour growth was found to cause a passive mechanical realignment of fibres at the tumour boundary from a random to a circumferential orientation. This is in accordance with experimental observations, thus demonstrating that such a response can be explained as purely mechanical. Finally, peritumoural fibre network anisotropy was found to produce anisotropic tumour morphology. The dependency of tumour morphology on the peritumoural microstructure was reduced by adding a load-bearing non-collagenous component to the fibre network constitutive equation. PMID- 26564174 TI - Investigating the effects of membrane deformability on artificial capsule adhesion to the functionalized surface. AB - Understanding, manipulating and controlling cellular adhesion processes can be critical in developing biomedical technologies. Adhesive mechanisms can be used to the target, pattern and separate cells such as leukocytes from whole blood for biomedical applications. The deformability response of the cell directly affects the rolling and adhesion behavior under viscous linear shear flow conditions. To that end, the primary objective of the present study was to investigate numerically the influence of capsule membrane's nonlinear material behavior (i.e. elastic-plastic to strain hardening) on the rolling and adhesion behavior of representative artificial capsules. Specifically, spherical capsules with radius of [Formula: see text] were represented using an elastic membrane governed by a Mooney-Rivlin strain energy functions. The surfaces of the capsules were coated with P-selectin glycoprotein-ligand-1 to initiate binding interaction with P selectin-coated planar surface with density of [Formula: see text] under linear shear flow varying from 100 to [Formula: see text]. The numerical model is based on the Immersed Boundary Method for rolling of deformable capsule in shear flow coupled with Monte Carlo simulation for receptor/ligand interaction modeled using Bell model. The results reveal that the mechanical properties of the capsule play an important role in the rolling behavior and the binding kinetics between the capsule contact surface and the substrate. The rolling behavior of the strain hardening capsules is relatively smoother and slower compared to the elastic plastic capsules. The strain hardening capsules exhibits higher contact area at any given shear rate compared to elastic-plastic capsules. The increase in contact area leads to decrease in rolling velocity. The capsule contact surface is not in complete contact with the substrate because of thin lubrication film that is trapped between the capsule and substrate. This creates a concave shape on the bottom surface of the capsule that is referred to as a dimple. In addition, the present study demonstrates that the average total bond force from the capsules lifetime increases by 37 % for the strain hardening capsules compared to elastic-plastic capsules at shear rate of [Formula: see text]. Finally, the model demonstrates the effect of finite membrane deformation on the coupling between hydrodynamic and receptor/ligand interaction. PMID- 26564176 TI - The Difficulties in the Management of Breast Cancer and Pregnancy. AB - INTRODUCTION: Breast cancer and pregnancy is rare. It is defined by the discovery of breast cancer during pregnancy or within one year after delivery. Throughout this study, we analyzed the characteristics of this entity with review of the literature. MATERIALS AND METHODS: We report through a retrospective study of breast cancer in pregnant women, a series of 11 cases collected at the oncology department in Sfax between 1994 and 2012. RESULT: The average age of our patients at diagnosis was 35 years. The average term of pregnancy was 22 weeks. Nine cases were diagnosed during pregnancy. The pregnancy outcome was well with babies in a good health, in 10 cases. The prognosis was excellent with complete remission after a mean follow of 39 months in 7 cases (2years-9years). CONCLUSION: The diagnosis of breast cancer in pregnant women is often delayed because of physiological changes of pregnancy and the young age which explain the poor prognosis of this entity. The prognosis was excellent in our series compared to the literature. PMID- 26564175 TI - Quality and performance measures of strain on intensive care capacity: a protocol for a systematic review. AB - BACKGROUND: The matching of critical care service supply with demand is fundamental for the efficient delivery of advanced life support to patients in urgent need. Mismatch in this supply/demand relationship contributes to "intensive care unit (ICU) capacity strain," defined as a time-varying disruption in the ability of an ICU to provide well-timed and high-quality intensive care support to any and all patients who are or may become critically ill. ICU capacity strain leads to suboptimal quality of care and may directly contribute to heightened risk of adverse events, premature discharges, unplanned readmissions, and avoidable death. Unrelenting strain on ICU capacity contributes to inefficient health resource utilization and may negatively impact the satisfaction of patients, their families, and frontline providers. It is unknown how to optimally quantify the instantaneous and temporal "stress" an ICU experiences due to capacity strain. METHODS: We will perform a systematic review to identify, appraise, and evaluate quality and performance measures of strain on ICU capacity and their association with relevant patient-centered, ICU-level, and health system-level outcomes. Electronic databases (i.e., MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, and the Agency of Healthcare Research and Quality (AHRQ) - National Quality Measures Clearinghouse (NQMC)) will be searched for original studies of measures of ICU capacity strain. Selected gray literature sources will be searched. Search themes will focus on intensive care, quality, operations management, and capacity. Analysis will be primarily narrative. Each identified measure will be defined, characterized, and evaluated using the criteria proposed by the US Strategic Framework Board for a National Quality Measurement and Reporting System (i.e., importance, scientific acceptability, usability, feasibility). DISCUSSION: Our systematic review will comprehensively identify, define, and evaluate quality and performance measures of ICU capacity strain. This is a necessary step towards understanding the impact of capacity strain on quality and performance in intensive care and to develop innovative interventions aimed to improve efficiency, avoid waste, and better anticipate impending capacity shortfalls. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42015017931. PMID- 26564177 TI - Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models. AB - AIMS/HYPOTHESIS: 'Glucotoxicity' is a term used to convey the negative effect of hyperglycaemia on beta cell function; however, the underlying molecular mechanisms that impair insulin secretion and gene expression are poorly defined. Our objective was to define the role of transcription factor v-ets avian erythroblastosis virus E26 oncogene homologue 1 (Ets-1) in beta cell glucotoxicity. METHODS: Primary islets and Min6 cells were exposed to high glucose and Ets-1 expression was measured. Recombinant adenovirus and transgenic mice were used to upregulate Ets-1 expression in beta cells in vitro and in vivo, and insulin secretion was assessed. The binding activity of H3/H4 histone on the Ets-1 promoter, and that of forkhead box (FOX)A2, FOXO1 and Ets-1 on the Pdx-1 promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assay. RESULTS: High glucose induced upregulation of Ets-1 expression and hyperacetylation of histone H3 and H4 at the Ets-1 gene promoter in beta cells. Ets-1 overexpression dramatically suppressed insulin secretion and biosynthesis both in vivo and in vitro. Besides, Ets-1 overexpression increased the activity of FOXO1 but decreased that of FOXA2 binding to the pancreatic and duodenal homeobox 1 (PDX-1) homology region 2 (PH2), resulting in inhibition of Pdx-1 promoter activity and downregulation of PDX-1 expression and activity. In addition, high glucose promoted the interaction of Ets-1 and FOXO1, and the activity of Ets-1 binding to the Pdx-1 promoter. Importantly, PDX-1 overexpression reversed the defect in pancreatic beta cells induced by Ets-1 excess, while knockdown of Ets-1 prevented hyperglycaemia-induced dysfunction of pancreatic beta cells. CONCLUSIONS/INTERPRETATION: Our observations suggest that Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in type 2 diabetes. PMID- 26564178 TI - Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies. AB - AIMS/HYPOTHESIS: The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible. METHODS: A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis. RESULTS: In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs. CONCLUSIONS/INTERPRETATION: This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes. PMID- 26564179 TI - Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes. AB - AIMS/HYPOTHESIS: Insulinoma-associated protein 2 (IA-2) is a major target of autoimmunity in type 1 diabetes. When first detected, IA-2-autoantibodies commonly bind epitopes in the juxtamembrane (JM) domain of IA-2 and antibody responses subsequently spread to the tyrosine phosphatase domain. Definition of structures of epitopes in the JM domain, and genetic requirements for autoimmunity to these epitopes, is important for our understanding of initiation and progression of autoimmunity. The aims of this study were to investigate the contribution of individual amino acids in the IA-2 JM domain to antibody binding to these epitopes and the role of HLA genotypes in determining epitope specificity. METHODS: Regions of the JM domain recognised by autoantibodies were identified by peptide competition and inhibitory effects of alanine substitutions of residues within the JM region. Antibody binding was determined by radioligand binding assays using sera from patients genotyped for HLA-DRB1 and -DQB1 alleles. RESULTS: Patients were categorised into two distinct groups of JM antibody reactivity according to peptide inhibition. Inhibition by substitutions of individual amino acids within the JM domain differed between patients, indicating heterogeneity in epitope recognition. Cluster analysis defined six groups of residues having similar inhibitory effects on antibody binding, with three clusters showing differences in patients affected or unaffected by peptide. One cluster demonstrated significant differences in antibody binding between HLA DRB1*04 and HLA-DRB1*07 patients and within DRB1*04 individuals; antibody recognition of a second cluster depended on expression of HLA-DQB1*0302. CONCLUSIONS/INTERPRETATION: The results identify amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity. PMID- 26564180 TI - RBP4 functions as a hepatokine in the regulation of glucose metabolism by the circadian clock in mice. AB - AIMS/HYPOTHESIS: As one of the key adipokines, retinol binding protein 4 (RBP4) is suggested to positively correlate with insulin resistance; however, not all clinical studies support this association. Although some explanations are proposed for this discrepancy, the temporal aspect of RBP4 secretion has not been considered. Aryl hydrocarbon receptor nuclear translocator-like (also known as BMAL1) and its target D site-binding protein (DBP) are both pivotal transcription factors of the circadian core clock. Given the overwhelming presence of circadian control in metabolism and the principal role of the liver in RBP4 secretion, we hypothesised that RBP4 may oscillate under the control of BMAL1 and act as a hepatokine, participating in the maintenance of glucose homeostasis by the circadian clock. METHODS: We used liver-specific Bmal1 (also known as Arntl) knockout mice and recombinant adenoviruses expressing short-hairpin RNA (shRNA) specific for Dbp or Rbp4 in the liver. RESULTS: RBP4 displayed diurnal oscillations in the liver and plasma, which were dampened in liver-specific-Bmal1 knockout mice. BMAL1 regulated hepatic RBP4 expression via its direct target, DBP. Hepatic knockdown of RBP4 or DBP increased whole-body insulin sensitivity in mice in a time-of-day-dependent manner. Conversely, hepatic overexpression of RBP4 reversed the insulin-sensitising effects of liver-specific depletion of BMAL1. CONCLUSIONS/INTERPRETATION: Our results not only provide a novel mechanism for circadian regulation of RBP4, but also unveil a critical role of RBP4, acting as a hepatokine in the regulation of glucose metabolism by the circadian clock. PMID- 26564181 TI - [Troponin elevation in ischemic stroke patients]. AB - Cerebrovascular and cardiovascular diseases are major causes of death and disability worldwide. Ischemic stroke is a frequent complication in cardiac diseases and, vice versa, cardiac complications commonly cause early clinical worsening and death after stroke. In the emergency setting, cardiac biomarkers (preferably troponin, cTn) are measured frequently in patients presenting with acute ischemic stroke. The measurement of cTn is recommended by the guidelines for early management of patients with acute ischemic stroke from the American Heart Association. In case of pathologic cTn elevation, physicians are confronted with diagnostic and therapeutic uncertainties. Up-to-date recommendations on interpretation and consecutive actions remain ambiguous because cTn elevations may originate from causes other than acute coronary disease and because clinical signs and symptoms of acute coronary disease may be obscured by neurological deficits of the stroke. The application of modern, high-sensitive cTn assays that detect even minor cTn elevations has rather aggravated the dilemma of how to interpret this finding in patients with ischemic stroke.This article gives an overview on possible mechanisms of the frequently observed cTn elevation in ischemic stroke patients and offers help on interpretation and meaningful actions. PMID- 26564182 TI - Impact of water composition on association of Ag and CeO2 nanoparticles with aquatic macrophyte Elodea canadensis. AB - In this study, the potential association of (citrate-stabilized) Ag (14.1 +/- 1.0 nm) and CeO2 (6.7 +/- 1.2 nm) engineered nanoparticles (ENPs), or their ionic counterparts, with the submerged aquatic plant Elodea canadensis, was examined and, in particular, parameters affecting the distribution of the nanoparticles (or metal ions) between plant biomass and the water phase were assessed using five distinct aqueous matrices (i.e. tap water, 10 % Hoagland's solution and three natural surface water samples). Individual plants were exposed to varying concentrations of Ag and CeO2 ENPs or Ag(+) and Ce(3+) ions during 72-h-lasting batch experiments. A dose-dependent increase of silver or cerium in plant biomass was observed for both the nanoparticles and the ions, whereby exposure to the latter systematically resulted in significantly higher biomass concentrations. Furthermore, the apparent plant uptake of CeO2 ENPs appeared to be higher than that for Ag ENPs when comparing similar exposure concentrations. These findings suggest that association with E. canadensis might be affected by particle characteristics such as size, composition, surface charge or surface coating. Moreover, the stability of the ENPs or ions in suspension/solution may be another important aspect affecting plant exposure and uptake. The association of the nanoparticles or ions with E. canadensis was affected by the physicochemical characteristics of the water sample. The silver biomass concentration was found to correlate significantly with the electrical conductivity (EC), dry residue (DR) and Cl(-), K, Na and Mg content in the case of Ag ENPs or with the EC, inorganic carbon (IC) and Cl(-), NO3 (-), Na and Mg content in the case of Ag(+) ions, whereas significant relationships between the cerium biomass concentration and the EC, DR, IC and Ca content or the pH, EC, DR, IC and Cl(-), Ca and Mg content were obtained for CeO2 ENPs or Ce(3+) ions, respectively. Results also indicated that the Ag ENPs and Ag(+) ions might potentially be toxic towards E. canadensis whereas no evidence of phytotoxicity was noted in the case of CeO2 ENPs or Ce(3+) ions. PMID- 26564183 TI - Mulberry trees conserved soil and protected water quality in the riparian zone of the Three Gorges Reservoir, China. AB - China's Sloping Land Conversion Program (SLCP) was designed to restore perennial plant cover on sloping land in western China, in part to protect the Three Gorges Reservoir (TGR). In this study, we examined use of white mulberry (Morus alba L.) in the SLCP to protect water quality and conserve soil. We established nine runoff monitoring plots divided among three categories (vegetable farming, fallow control, and mulberry plantation) on a bank of the Liangtan River situated at the western margin of the TGR. The land had been used previously by farmers for growing vegetables. We found that soil loss and surface water runoff were lowest in the mulberry plots and highest in the vegetable plots. We used inductively coupled plasma atomic emission spectroscopy (ICP-AES) to assess the concentration of selected heavy metal pollution indicators (Zn, Hg, As, Ni, Pb, Cr, Cd, and Cu) in the monitoring plot soils at the beginning of the experiment in May 2009. The heavy metals were assessed again at the end of the experiment in October 2012, and we found that the concentrations of these pollutants had been reduced in all fallow and mulberry plots, and to the greatest extent in the mulberry plots. We found that levels of Hg, Pb, and Cu increased in the vegetable plots. For these reasons, we conclude that riparian mulberry plantations are useful for reducing rapid runoff of storm water, conserving soil, and sequestering heavy metal pollutants in the TGR region. PMID- 26564184 TI - Reactions to cadmium stress in a cadmium-tolerant variety of cabbage (Brassica oleracea L.): is cadmium tolerance necessarily desirable in food crops? AB - Cadmium is a cumulative, chronic toxicant in humans for which the main exposure pathway is via plant foods. Cadmium-tolerant plants may be used to create healthier food products, provided that the tolerance is associated with the exclusion of Cd from the edible portion of the plant. An earlier study identified the cabbage (Brassica oleracea L.) variety, Pluto, as relatively Cd tolerant. We exposed the roots of intact, 4-week-old seedlings of Pluto to Cd (control ~1 mg L(-1) treatment 500 MUg L(-1)) for 4 weeks in flowing nutrient solutions and observed plant responses. Exposure began when leaf 3 started to emerge, plants were harvested after 4 weeks of Cd exposure and the high Cd treatment affected all measured parameters. The elongation rate of leaves 4-8, but not the duration of elongation was reduced; consequently, individual leaf area was also reduced (P < 0.001) and total leaf area and dry weight were approximately halved. A/C i curves immediately before harvest showed that Cd depressed the photosynthetic capacity of the last fully expanded leaf (leaf 5). Despite such large impairments of the source and sink capacities, specific leaf weight and the partitioning of photosynthate between roots, stems and leaves were unaffected (P > 0.1). Phytochelatins (PCs) and glutathione (GSH) were present in the roots even at the lowest Cd concentration in the nutrient medium, i.e. ~1 MUg Cd L(-1), which would not be considered contaminated if it were a soil solution. The Cd concentration in these roots was unexpectedly high (5 mg kg(-1) DW) and the molar ratio of -SH (in PCs plus GSH) to Cd was large (>100:1). In these control plants, the Cd concentration in the leaves was 1.1 mg kg(-1) DW, and PCs were undetectable. For the high Cd treatment, the concentration of Cd in roots exceeded 680 mg kg(-1) DW and the molar -SH to Cd ratio fell to ~1.5:1. For these plants, Cd flooded into the leaves (107 mg kg(-1) DW) where it probably induced synthesis of PCs, and the molar -SH to Cd ratio was ~3:1. Nonetheless, this was insufficient to sequester all the Cd, as evidenced by the toxic effects on photosynthesis and growth noted above. Lastly, Cd accumulation in the leaves was associated with lowered concentrations of some trace elements, such as Zn, a combination of traits that is highly undesirable in food plants. PMID- 26564185 TI - Large scale groundwater flow and hexavalent chromium transport modeling under current and future climatic conditions: the case of Asopos River Basin. AB - In recent years, high concentrations of hexavalent chromium, Cr(VI), have been observed in the groundwater system of the Asopos River Basin, raising public concern regarding the quality of drinking and irrigation water. The work described herein focuses on the development of a groundwater flow and Cr(VI) transport model using hydrologic, geologic, and water quality data collected from various sources. An important dataset for this goal comprised an extensive time series of Cr(VI) concentrations at various locations that provided an indication of areas of high concentration and also served as model calibration locations. Two main sources of Cr(VI) contamination were considered in the area: anthropogenic contamination originating from Cr-rich industrial wastes buried or injected into the aquifer and geogenic contamination from the leaching process of ophiolitic rocks. The aquifer's response under climatic change scenario A2 was also investigated for the next two decades. Under this scenario, it is expected that rainfall, and thus infiltration, will decrease by 7.7 % during the winter and 15 % during the summer periods. The results for two sub-scenarios (linear and variable precipitation reduction) that were implemented based on A2 show that the impact on the study aquifer is moderate, resulting in a mean level decrease less than 1 m in both cases. The drier climatic conditions resulted in higher Cr(VI) concentrations, especially around the industrial areas. PMID- 26564186 TI - Assessing trace metal pollution through high spatial resolution of surface sediments along the Tunis Gulf coast (southwestern Mediterranean). AB - Tunis Gulf (northern Tunisia, Mediterranean Sea) is of great economic importance due to its abundant fish resources. Rising urbanization and industrial development in the surrounding area have resulted in an increase in untreated effluents and domestic waste discharged into the gulf via its tributary streams. Metal (Cd, Pb, Hg, Cu, Zn, Fe, and Mn) and major element (Mg, Ca, Na, and K) concentrations were measured in the grain fine fraction <63 MUm by atomic absorption spectrophotometry. Results showed varying spatial distribution patterns for metals, indicating complex origins and controlling factors such as anthropogenic activities. Sediment metal concentrations are ranked as follows: Fe > Mg > Zn > Mn > Pb > Cu > Cd > Hg. Metals tend to be concentrated in proximity to source points, suggesting that the mineral enrichment elements come from sewage of coastal towns and pollution from industrial dumps and located along local rivers, lagoons, and on the gulf shore itself. This study showed that trace metal and major element concentrations in surface sediments along the Tunis Gulf shores were lower than those found in other coastal areas of the Mediterranean Sea. PMID- 26564187 TI - Bioaccessibility of heavy metals in vegetables and its association with the physicochemical characteristics. AB - The bioaccessibilites of heavy metals in vegetables grown around a waste incinerator site were estimated using the physiologically based extraction test (PBET) method, to assess potential health risk to the local consumers. The average gastric and intestinal bioaccessibilities of Cd, Cr, Cu, Ni, and Pb in vegetables varied within 3.2-9.4 and 0.8-5.3 %, 1.4-2.3 and 1.1-1.9 %, 25-46 and 13-26 %, 6.6-30 and 2.6-5.3 %, 11-29 and 7.1-23 %, respectively. Strong negative correlations were found between electrochemical potential (DeltaE 0) and bioaccessibility for leaf mustard samples (r (2) = 0.857) and leaf lettuce samples (r (2) = 0.696). In addition, softness index (sigmap) and electrochemical potential (DeltaE 0) exhibited a moderate but not significant relationship with bioaccessibilities on the basis of the multiple regression analysis (0.05 < p < 0.1). The total bioaccessible target hazard quotient (TBTHQ) of the five heavy metals was 2.5, with Pb being the major risk contributor. According to the TBTHQs of each group of vegetables, local consumers are experiencing adverse health effects by consuming most of the vegetables around waste-incinerator site. PMID- 26564188 TI - Using natural Chinese zeolite to remove ammonium from rainfall runoff following urea fertilization of a paddy rice field. AB - The potential of natural Chinese zeolite to remove ammonium from rainfall runoff following urea applications to a paddy rice field is assessed in this study. Laboratory batch kinetic and isotherm experiments were carried out first to investigate the ammonium adsorption capacity of the natural zeolite. Field experiments using zeolite adsorption barriers installed at drain outlets in a paddy rice field were also carried out during natural rainfall events to evaluate the barrier's dynamic removal capacity of ammonium. The results demonstrate that the adsorption kinetics are accurately described by the Elovich model, with a coefficient of determination (R (2)) ranging from 0.9705 to 0.9709, whereas the adsorption isotherm results indicate that the Langmuir-Freundlich model provides the best fit (R (2) = 0.992) for the equilibrium data. The field experiments show that both the flow rate and the barrier volume are important controls on ammonium removal from rainfall runoff. A low flow rate leads to a higher ammonium removal efficiency at the beginning of the tests, while a high flow rate leads to a higher quantity of ammonium adsorbed over the entire runoff process. PMID- 26564189 TI - Migration and transformation rule of heavy metals in sludge during hydrolysis for protein extraction. AB - The content and speciation of heavy metals can fundamentally affect the hydrolysis of sludge. This research study investigates the migration and transformation rule of heavy metals during the hydrolysis process by measuring the content of exchangeables (F1), bound to carbonates (F2), bound to Fe-Mn oxides (F3), bound to organic matter (F4), and residuals (F5) under different periods of time undergoing hydrolysis. The results show that the hydrolysis process generally stabilized Cu, Zn, Mn, Ni, Pb, Cr, and As by transforming the unstable states into structurally stable states. Such transformations and stabilization were primarily caused by the changes in local metal ion environment and bonding structure, oxidation of sulfides, pyrolyzation of organic matter, and evaporation of resulting volatile materials. An X-ray diffractometry (XRD) of the residuals conducted after hydrolysis indicated that hydrolysis did have a significant influence on the transportation and transformation of heavy metals. PMID- 26564191 TI - Thermodynamic analysis of in situ gasification-chemical looping combustion (iG CLC) of Indian coal. AB - Chemical looping combustion (CLC) is an inherent CO2 capture technology. It is gaining much interest in recent years mainly because of its potential in addressing climate change problems associated with CO2 emissions from power plants. A typical chemical looping combustion unit consists of two reactors-fuel reactor, where oxidation of fuel occurs with the help of oxygen available in the form of metal oxides and, air reactor, where the reduced metal oxides are regenerated by the inflow of air. These oxides are then sent back to the fuel reactor and the cycle continues. The product gas from the fuel reactor contains a concentrated stream of CO2 which can be readily stored in various forms or used for any other applications. This unique feature of inherent CO2 capture makes the technology more promising to combat the global climate changes. Various types of CLC units have been discussed in literature depending on the type of fuel burnt. For solid fuel combustion three main varieties of CLC units exist namely: syngas CLC, in situ gasification-CLC (iG-CLC) and chemical looping with oxygen uncoupling (CLOU). In this paper, theoretical studies on the iG-CLC unit burning Indian coal are presented. Gibbs free energy minimization technique is employed to determine the composition of flue gas and oxygen carrier of an iG-CLC unit using Fe2O3, CuO, and mixed carrier-Fe2O3 and CuO as oxygen carriers. The effect of temperature, suitability of oxygen carriers, and oxygen carrier circulation rate on the performance of a CLC unit for Indian coal are studied and presented. These results are analyzed in order to foresee the operating conditions at which economic and smooth operation of the unit is expected. PMID- 26564190 TI - Advanced low carbon-to-nitrogen ratio wastewater treatment by electrochemical and biological coupling process. AB - Nitrogen pollution in ground and surface water significantly affects the environment and its organisms, thereby leading to an increasingly serious environmental problem. Such pollution is difficult to degrade because of the lack of carbon sources. Therefore, an electrochemical and biological coupling process (EBCP) was developed with a composite catalytic biological carrier (CCBC) and applied in a pilot-scale cylindrical reactor to treat wastewater with a carbon-to nitrogen (C/N) ratio of 2. The startup process, coupling principle, and dynamic feature of the EBCP were examined along with the effects of hydraulic retention time (HRT), dissolved oxygen (DO), and initial pH on nitrogen removal. A stable coupling system was obtained after 51 days when plenty of biofilms were cultivated on the CCBC without inoculation sludge. Autotrophic denitrification, with [Fe(2+)] and [H] produced by iron-carbon galvanic cells in CCBC as electron donors, was confirmed by equity calculation of CODCr and nitrogen removal. Nitrogen removal efficiency was significantly influenced by HRT, DO, and initial pH with optimal values of 3.5 h, 3.5 +/- 0.1 mg L(-1), and 7.5 +/- 0.1, respectively. The ammonia, nitrate, and total nitrogen (TN) removal efficiencies of 90.1 to 95.3 %, 90.5 to 99.0 %, and 90.3 to 96.5 % were maintained with corresponding initial concentrations of 40 +/- 2 mg L(-1) (NH3-N load of 0.27 +/- 0.01 kg NH3-N m(-3) d(-1)), 20 +/- 1 mg L(-1), and 60 +/- 2 mg L(-1) (TN load of 0.41 +/- 0.02 kg TN m(-3) d(-1)). Based on the Eckenfelder model, the kinetics equation of the nitrogen transformation along the reactor was N e = N 0 exp ( 0.04368 h/L(1.8438)). Hence, EBCP is a viable method for advanced low C/N ratio wastewater treatment. PMID- 26564192 TI - Sensory determinants of valve rhythm dynamics provide in situ biodetection of copper in aquatic environments. AB - This study successfully applied an improved valvometry technique to measure waterborne copper (Cu), based on valve activity dynamics of the freshwater clam Corbicula fluminea. The improved valvometry technique allows the use of free range bivalves and avoids causing stresses from experimental artifacts. The proposed daily valve rhythm models and a toxicodynamics-based Hill model were linked to predict valve dynamic responses under different Cu exposures with a circadian valve rhythm endpoint. Cu-specific detection threshold was 5.6 (95 % CI 2.1-9.3) and 19.5 (14.6-24.3) MUg L(-1) for C. fluminea, based on response times of 300 and 30 min, respectively. Upon exposure to Cu concentrations in excess of 50 MUg L(-1), the alteration of valve rhythm behavior was correlated with Cu concentration within 30 min, indicating notable sensing ability. This study outlines the feasibility of an in situ early warning dynamic biomonitoring system for detection of waterborne Cu based on circadian valve activities of C. fluminea. PMID- 26564193 TI - Photocatalytic degradation of phenol using Ag core-TiO2 shell (Ag@TiO2) nanoparticles under UV light irradiation. AB - Ag@TiO2 nanoparticles were synthesized by one pot synthesis method with postcalcination. These nanoparticles were tested for their photocatalytic efficacies in degradation of phenol both in free and immobilized forms under UV light irradiation through batch experiments. Ag@TiO2 nanoparticles were found to be the effective photocatalysts for degradation of phenol. The effects of factors such as pH, initial phenol concentration, and catalyst loading on phenol degradation were evaluated, and these factors were found to influence the process efficiency. The optimum values of these factors were determined to maximize the phenol degradation. The efficacy of the nanoparticles immobilized on cellulose acetate film was inferior to that of free nanoparticles in UV photocatalysis due to light penetration problem and diffusional limitations. The performance of fluidized bed photocatalytic reactor operated under batch with recycle mode was evaluated for UV photocatalysis with immobilized Ag@TiO2 nanoparticles. In the fluidized bed reactor, the percentage degradation of phenol was found to increase with the increase in catalyst loading. PMID- 26564194 TI - Event mean concentration and first flush effect from different drainage systems and functional areas during storms. AB - This study aimed to investigate the characteristics of the event mean concentration (EMC) and first flush effect (FFE) during typical rainfall events in outfalls from different drainage systems and functional areas. Stormwater outfall quality data were collected from five outfalls throughout Fuzhou City (China) during 2011-2012. Samples were analyzed for water quality parameters, such as COD, NH3-N, TP, and SS. Analysis of values indicated that the order of the event mean concentrations (EMCs) in outfalls was intercepting combined system > direct emission combined system > separated system. Most of the rainfall events showed the FFE in all outfalls. The order of strength of the FFE was residential area of direct emission combined system > commercial area of separated system > residential area of intercepting combined system > office area of separated system > residential area of separated system. Results will serve as guide in managing water quality to reduce pollution from drainage systems. PMID- 26564195 TI - Fouling analysis of membrane bioreactor treating antibiotic production wastewater at different hydraulic retention times. AB - Membrane fouling, including foulants and factors, was investigated during hydraulic retention time (HRT) optimization of a membrane bioreactor (MBR) that treated wastewater from the production of antibiotics. The results showed that HRT played an important role in membrane fouling. Trans-membrane pressure (TMP), membrane flux, and resistance were stable at -6 kPa, 76 L m-2 h-1 bar-1, and 4.5 * 1012 m-1 when HRT was at 60, 48, and 36 h, respectively. Using Fourier transform infrared spectroscopy, foulants were identified as carbohydrates and proteins, which correlated with effluent organic matter and effluent chemical oxygen demand (COD) compounds. Therefore, membrane fouling trends would benefit from low supernatant COD (378 mg L-1) and a low membrane removal rate (26 %) at a HRT of 36 h. Serious membrane fouling at 72 and 24 h was related to soluble microbial products and extracellular polymeric substances in mixed liquor, respectively. Based on the TMP decrease and flux recovery after physical and chemical cleaning, irremovable fouling aggravation was related to extracellular polymeric substances' increase and soluble microbial products' decrease. According to changes in the specific oxygen uptake rate (SOUR) and mixed liquor suspended solids (MLSSs) during HRT optimization in this study, antibiotic production wastewater largely inhibited MLSS growth, which only increased from 4.5 to 5.0 g L-1 when HRT was decreased from 72 to 24 h, but did not limit sludge activity. The results of a principal component analysis highlighted both proteins and carbohydrates in extracellular polymeric substances as the primary foulants. Membrane fouling associated with the first principal component was positively related to extracellular polymeric substances and negatively related to soluble microbial products. Principal component 2 was primarily related to proteins in the influent. Additional membrane fouling factors included biomass characteristics, operational conditions, and feed characteristics. PMID- 26564196 TI - Adsorption of bentazone herbicide onto mesoporous silica: application to environmental water purification. AB - Within the last few years, the presence of bentazone herbicide has been observed in many water resources. For the first time, removal of bentazone using mesoporous silica was investigated revealing reversible adsorption. The adsorption isotherm was well described using the Freundlich model. The affinity towards bentazone is strongly affected by pH in the range of 2-7, decreasing with the increase of the pH, becoming negligible at the neutrality. Regeneration of the adsorbent was possible, and a recovery as high as 70 % was obtained using CH3OH-NaOH solution. Furthermore, appreciable recovery (47 %) was also obtained using water. Applications on the purification of lake water and wastewaters, both characterized by a significant organic carbon load, spiked with 2 mg L(-1) bentazone were tested, observing removal yields in the range of 61-73 %. Taking advantage of the fast adsorption kinetics observed, an in-flow purification treatment was set-up, with quantitative removal of bentazone from polluted water. PMID- 26564197 TI - Characterization of Cd translocation and accumulation in 19 maize cultivars grown on Cd-contaminated soil: implication of maize cultivar selection for minimal risk to human health and for phytoremediation. AB - Maize (Zea mays) has low Cd accumulation in grains and a high biomass compared to other crops. The capacities for Cd accumulation in different maize cultivars are, however, not fully understood. To reduce human health risk from maize grown in Cd contaminated soil and to provide promising maize cultivars for the phytoremediation of Cd-polluted soil, a field experiment was conducted to screen low-Cd- and high-Cd-accumulation maize cultivars by evaluating the yield, Cd uptake, translocation, and accumulation differences among 19 maize cultivars. There were differences in straw dry weight (DW), root DW, and yield among the 19 cultivars. The cultivars Yudan19, Zhengda999, and Xianyu508 had a higher production compared to that of the other cultivars. The Cd concentrations in the roots were much higher than those in the straws and grains in all cultivars. The Cd accumulation factors (AFS) decreased in the order of accumulation factors in root (AFrs) > accumulation factors in straw (AFss) > accumulation factors in grain (AFgs). The Cd translocation factors (TFs) from root to straw (TFrs) were significantly (p < 0.05) larger than those from straw to grain (TFsg) among all of the cultivars. The TFs for all of the cultivars was less than 1, and the lowest TFsg (0.23) was found in cultivar Xiangyongdan3. The correlation analysis indicated that Cd concentrations in straws showed a significant (p < 0.01) as well as positive correlation with TFrs while a negative correlation with TFsg (p < 0.01). Moreover, Cd accumulation in different tissues decreased in the order straw > grain > root. Among the 19 maize cultivars, Jixiang2118 and Kangnong18 accumulated the highest Cd amount in the aboveground tissues, and the corresponding values were 7,206.51 and 6,598.68 mg hm(-2), respectively. A hierarchical cluster analysis based on the Cd concentrations in grains and straws classified the 19 maize cultivars into four and two groups for a 0.4 minimum distance between clusters, respectively. Yudan19, Zhengda999, and Xianyu508 can be classified into one group in which low Cd in grains meeting the Cd tolerance limit in foods set by China National Standard, suggesting that those cultivars are safety for food and human health. However, Jixiang2118 and Kangnong18 can be classified as another group with potential application for phytoremediation in slightly or moderately Cd-polluted soil because of the high Cd accumulation in the aboveground tissues. PMID- 26564198 TI - Brain cholinesterase reactivation as a marker of exposure to anticholinesterase pesticides: a case study in a population of yellow-legged gull Larus michahellis (Naumann, 1840) along the northern coast of Portugal. AB - Between late 2010 to early 2011, an increased mortality in gulls was observed along the northern coast of Portugal, with individuals exhibiting neurologic disorders consistent with an eventual anticholinesterase pesticide poisoning event. To clarify if this mortality was related to organophosphate (OP) and/or carbamate (CB) poisoning, chemical and spontaneous cholinesterase (ChE) reactivation was tested in the brain of the yellow-legged gull (Larus michahellis). Initial brain ChE activity in L. michahellis was 40.92 +/- 5.23 U/mg of protein (average +/- SE). Following chemical and spontaneous reactivation, ChE activity increased in average 70.38 +/- 48.59% and 131.95 +/- 92.64%, respectively. ChE reactivation was found to decrease at increasing concentrations of the oxime pyridine-2-aldoxime methochloride and dilution factor, underscoring the importance of first optimizing the assay conditions prior to its use on bird species. These results suggest that birds analysed could have been exposed to OP and CB pesticide compounds and that in most cases CB exposure appeared to be the main cause of birds poisoning. These results are an important contribution to environmental monitoring as it demonstrates the suitability of L. michaellis as sentinel species of OP and CB pesticides within an urban environment. PMID- 26564199 TI - Dynamics and polyphasic characterization of odor-producing cyanobacterium Tychonema bourrellyi from Lake Erhai, China. AB - The previous studies indicated that Tychonema-like strains from Lake Erhai could release geosmin so that the species was listed as the potential harmful cyanobacteria influencing the drinking water safety around Lake Erhai. But, the dynamics and biological information of this species were too limited. In this study, the polyphasic approach was used to reveal its biological characterization and the dynamics in Lake Erhai. The characters of trichomes, including filaments with solitary or bundle state, reddish-brown or blue-green color, planktonic habitat, and presence of keritomized content, were examined by the microscopic method. The 16S rDNA sequences of these strains were used for phylogenetic analysis and molecular identification. The strains were morphologically classified as Tychonema bourrellyi, and geosmin and beta-ionone were identified as the major volatile substances using gas chromatography-mass spectrometry (GC MS) analysis. No strains of T. bourrellyi were found to produce microcystin by the HPLC and mcy gene approaches. Cell numbers at 12 sampling sites in Lake Erhai were shown as an average of 3 * 10(4) cells L(-1) in 2009 and 2010. The obvious peaks occurred in July and August each year. This was the first report on occurrence of T. bourrellyi from outside of Europe, and T. bourrellyi was also a newly recorded species in China. Such a result demonstrated that T. bourrellyi could distribute extending from cold waters in North Europe to the warm waters in subtropical regions. It was interesting to observe the coincidence of the occurrence of T. bourrellyi with slightly eutrophicated waters since Lake Erhai had been regarded as an early phase of eutrophicated lake. PMID- 26564200 TI - Phenotypes of orthostatic blood pressure behaviour and association with visual acuity. AB - BACKGROUND: Manifestations of neurocardiovascular instability (NCVI), including orthostatic hypotension (OH) orthostatic hypertension (OHTN) and impaired blood pressure variability (BPV), have been associated with cardiovascular (CV) events. The eye is highly vascular and we propose an ideal target end organ to investigate pathological implications of NCVI. OBJECTIVE: To identify and define clinically applicable phenotypes of orthostatic blood pressure (BP) behaviour, analogous to OH, OHTN, and orthostatic BPV and to investigate their relationship to vision. METHODS: Wave one data from the Irish Longitudinal Study on Ageing (TILDA) were used. Orthostatic BP (OBP) phenotypes were identified and defined from beat-to-beat BP data, measured by digital photoplethysmography during an active stand (AS) lasting 110 s (s). Visual acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (EDTRS) LogMAR chart. The relationship between OBP phenotypes and VA in 4355 adults aged >=50 years was investigated through multivariate linear regression models. RESULTS: There was a wide fluctuation in the prevalence of OH and OHTN up to 20 s after standing. After 30 s, four distinct OBP phenotypes were identified: in 70 % BP stabilised to within 20/10 mmHg of baseline BP, 4 % had persistent OH, 2 % had persistent OHTN and 25 % had exaggerated orthostatic blood pressure variability BPV. Systolic BPV was associated with worse VA (P = 0.02) as was diastolic BPV (P = 0.03), following adjustment for demographics, health behaviours, self-report eye diseases and diabetes, uncorrected refractive error, objective hypertension and antihypertensives. CONCLUSIONS: The hypothesis that NCVI may independently modulate CV risk is supported the independent association of exaggerated BPV and worse VA. PMID- 26564202 TI - An AhR-Luciferase Adenovirus Infection System for Rapid Screening of Dioxins in Soils. AB - Our goal was to develop a fast-screening method for measuring dioxin levels in soils. The adenovirus (Ad)-dioxin-responsive (DR) bioassay system (AdEasy-6XDRE TATA-Luc) combined with a fast-cleanup system was examined under conventional conditions (i.e., with incubation at 37 degrees C) and three alternative conditions [incubation at 37 degrees C with addition of phorbol-12-myristate-13 acetate (PMA), incubation at 33 degrees C, and incubation at 33 degrees C with addition of PMA]. The best conditions for carrying out the Ad-DR bioassay was 33 degrees C and no addition of PMA. The background level of soil dioxins determined by the chemical assay [6.49 ng I-TEQ/kg dry weight (dw)] was well correlated (Pearson's r = 0.873, p < 0.001) with that by the Ad-DR bioassay [expressed in ng bioanalytical equivalents (BEQ) 81.1 ng BEQ/kg dw] (n = 17). When surveyed in contaminated soil samples (n = 114) from industrial areas by the Ad-DR bioassay, dioxin levels were 117, 102, 98.5, and 112 ng BEQ/kg dw, respectively, in northern, central, southern, and eastern Taiwan. PMID- 26564201 TI - Combined ultra-low input mRNA and whole-genome sequencing of human embryonic stem cells. AB - BACKGROUND: Next Generation Sequencing has proven to be an exceptionally powerful tool in the field of genomics and transcriptomics. With recent development it is nowadays possible to analyze ultra-low input sample material down to single cells. Nevertheless, investigating such sample material often limits the analysis to either the genome or transcriptome. We describe here a combined analysis of both types of nucleic acids from the same sample material. METHODS: The method described enables the combined preparation of amplified cDNA as well as amplified whole-genome DNA from an ultra-low input sample material derived from a sub colony of in-vitro cultivated human embryonic stem cells. cDNA is prepared by the application of oligo-dT coupled magnetic beads for mRNA capture, first strand synthesis and 3'-tailing followed by PCR. Whole-genome amplified DNA is prepared by Phi29 mediated amplification. Illumina sequencing is applied to short fragment libraries prepared from the amplified samples. RESULTS: We developed a protocol which enables the combined analysis of the genome as well as the transcriptome by Next Generation Sequencing from ultra-low input samples. The protocol was evaluated by sequencing sub-colony structures from human embryonic stem cells containing 150 to 200 cells. The method can be adapted to any available sequencing system. CONCLUSIONS: To our knowledge, this is the first report where sub-colonies of human embryonic stem cells have been analyzed both at the genomic as well as transcriptome level. The method of this proof of concept study may find useful practical applications for cases where only a limited number of cells are available, e.g. for tissues samples from biopsies, tumor spheres, circulating tumor cells and cells from early embryonic development. The results we present demonstrate that a combined analysis of genomic DNA and messenger RNA from ultra low input samples is feasible and can readily be applied to other cellular systems with limited material available. PMID- 26564203 TI - Crystal structure of the homocysteine methyltransferase MmuM from Escherichia coli. AB - Homocysteine S-methyltransferases (HMTs, EC 2.1.1.0) catalyse the conversion of homocysteine to methionine using S-methylmethionine or S-adenosylmethionine as the methyl donor. HMTs play an important role in methionine biosynthesis and are widely distributed among micro-organisms, plants and animals. Additionally, HMTs play a role in metabolite repair of S-adenosylmethionine by removing an inactive diastereomer from the pool. The mmuM gene product from Escherichia coli is an archetypal HMT family protein and contains a predicted zinc-binding motif in the enzyme active site. In the present study, we demonstrate X-ray structures for MmuM in oxidized, apo and metallated forms, representing the first such structures for any member of the HMT family. The structures reveal a metal/substrate-binding pocket distinct from those in related enzymes. The presented structure analysis and modelling of co-substrate interactions provide valuable insight into the function of MmuM in both methionine biosynthesis and cofactor repair. PMID- 26564204 TI - An integrated biochemical system for nitrate assimilation and nitric oxide detoxification in Bradyrhizobium japonicum. AB - Rhizobia are recognized to establish N2-fixing symbiotic interactions with legume plants. Bradyrhizobium japonicum, the symbiont of soybeans, can denitrify and grow under free-living conditions with nitrate (NO3 (-)) or nitrite (NO2 (-)) as sole nitrogen source. Unlike related bacteria that assimilate NO3 (-), genes encoding the assimilatory NO3 (-) reductase (nasC) and NO2 (-) reductase (nirA) in B. japonicum are located at distinct chromosomal loci. The nasC gene is located with genes encoding an ABC-type NO3 (-) transporter, a major facilitator family NO3 (-)/NO2 (-) transporter (NarK), flavoprotein (Flp) and single-domain haemoglobin (termed Bjgb). However, nirA clusters with genes for a NO3 (-)/NO2 ( )-responsive regulator (NasS-NasT). In the present study, we demonstrate NasC and NirA are both key for NO3 (-) assimilation and that growth with NO3 (-), but not NO2 (-) requires flp, implying Flp may function as electron donor to NasC. In addition, bjgb and flp encode a nitric oxide (NO) detoxification system that functions to mitigate cytotoxic NO formed as a by-product of NO3 (-) assimilation. Additional experiments reveal NasT is required for NO3 (-) responsive expression of the narK-bjgb-flp-nasC transcriptional unit and the nirA gene and that NasS is also involved in the regulatory control of this novel bipartite assimilatory NO3 (-)/NO2 (-) reductase pathway. PMID- 26564205 TI - Peroneal tendon dislocation. AB - INTRODUCTION: Peroneal tendon instability goes often mis- or undiagnosed in the acute setting of evaluation of ankle sprains. The current article provides a concise overview regarding peroneal tendon instability. METHODS: A proper history, clinical assessment and imaging help to establish the correct diagnosis. Conventional radiography, ultrasound, magnetic resonance imaging and sometimes computed tomography may help to elucidate the pattern of injury. RESULTS: Nonoperative treatment can be considered in the acute setting. However, high failure rates up to 50 % have been reported in the literature. This is even better reflected in the chronic stage of peroneal instability, in which most of the patients need surgical treatment. In contrast, surgical treatment attempts to restore structural stabilization of the peroneal tendon and retinacular complex. The simple reconstruction and repair of the damaged retinacular structures and tendons achieve excellent results. In patients with structural abnormalities of the retromalleolar groove, groove-deepening procedures may be considered. Most of chronic personal tendon instabilities need to be addressed by surgery due to the frustrating results obtained by nonoperative measures. However, reconstruction of the tendinous and retinacular structures can yield good-to-excellent outcomes. PMID- 26564206 TI - Subantimicrobial-dose doxycycline monohydrate in dermatology. AB - Subantimicrobial doxycycline is an anti-inflammatory drug that decreases cathelicidin, kallikrein 5, reactive oxygen species, nitric oxide, and matrix metalloproteinases. Clinical trials demonstrated a comparable efficacy to 100-mg doxycycline in papulopustular rosacea with improvement of inflammatory lesions, quality of life, and improved safety profile. Case series and case reports suggested efficacy in other inflammatory skin diseases. The response of papulopustular rash during targeted anticancer therapies is mixed. Further studies are needed. PMID- 26564207 TI - [EOS imaging acquisition system : 2D/3D diagnostics of the skeleton]. AB - The application spectrum of the EOS imaging acquisition system is versatile. It is especially useful in the diagnostics and planning of corrective surgical procedures in complex orthopedic cases. The application is indicated when assessing deformities and malpositions of the spine, pelvis and lower extremities. It can also be used in the assessment and planning of hip and knee arthroplasty. For the first time physicians have the opportunity to conduct examinations of the whole body under weight-bearing conditions in order to anticipate the effects of a planned surgical procedure on the skeletal system as a whole and therefore on the posture of the patient. Compared to conventional radiographic examination techniques, such as x-ray or computed tomography, the patient is exposed to much less radiation. Therefore, the pediatric application of this technique can be described as reasonable. PMID- 26564208 TI - Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema. AB - Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent beta-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067+/-0.008 ml/cmH20 compared with 0.035+/-0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051+/-0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD. PMID- 26564209 TI - Stereoscopic perception of 3-D images by patients after surgery for esotropia. AB - PURPOSE: Patients with esotropia (ET) have generally poor stereopsis; however, it is not clear whether they can see the recently developed 3-D images stereoscopically. We investigated the ability of postoperative ET patients to have stereoscopic perception of 3-D attraction images which have large crossed disparities, and also 3-D movies which have generally small uncrossed disparities. METHODS: Twenty-seven ET patients (infantile ET = 12, late-onset ET = 15) were examined postoperatively. They were examined with the 4-dot test, Titmus fly test, and questionnaires to determine whether they had stereoscopic vision when observing 3-D attraction images and 3-D movies. McNemar tests were used for statistical evaluations. RESULTS: The number of patients who passed the Titmus fly test was smaller than the number that were able to see 3-D attraction images stereoscopically (fly test 13; 48%, 3-D attraction 22; 81%; P = 0.016). However, the number was not significantly different from that of those who could perceive 3-D movies stereoscopically. The number of patients who passed the Titmus fly test was significantly smaller than the number who can perceive 3-D attraction images stereoscopically in the infantile ET group (fly test 2, 17%, 3 D attraction 10, 83%; P = 0.013) but was not different in the late-onset ET group postoperatively. The minimum angle of fusion for the 4-dot test was smaller in the Titmus fly-positive patients than in the Titmus fly-negative patients (P = 0.03). CONCLUSIONS: These results suggest that children who cannot pass the Titmus fly test might be able to experience 3-D attractions stereoscopically but not be able to see 3-D movies stereoscopically. PMID- 26564210 TI - Understanding why resistant bacteria are associated with higher mortality in ICU patients. PMID- 26564211 TI - The reliability of the Glasgow Coma Scale: a systematic review. AB - INTRODUCTION: The Glasgow Coma Scale (GCS) provides a structured method for assessment of the level of consciousness. Its derived sum score is applied in research and adopted in intensive care unit scoring systems. Controversy exists on the reliability of the GCS. The aim of this systematic review was to summarize evidence on the reliability of the GCS. METHODS: A literature search was undertaken in MEDLINE, EMBASE and CINAHL. Observational studies that assessed the reliability of the GCS, expressed by a statistical measure, were included. Methodological quality was evaluated with the consensus-based standards for the selection of health measurement instruments checklist and its influence on results considered. Reliability estimates were synthesized narratively. RESULTS: We identified 52 relevant studies that showed significant heterogeneity in the type of reliability estimates used, patients studied, setting and characteristics of observers. Methodological quality was good (n = 7), fair (n = 18) or poor (n = 27). In good quality studies, kappa values were >=0.6 in 85%, and all intraclass correlation coefficients indicated excellent reliability. Poor quality studies showed lower reliability estimates. Reliability for the GCS components was higher than for the sum score. Factors that may influence reliability include education and training, the level of consciousness and type of stimuli used. CONCLUSIONS: Only 13% of studies were of good quality and inconsistency in reported reliability estimates was found. Although the reliability was adequate in good quality studies, further improvement is desirable. From a methodological perspective, the quality of reliability studies needs to be improved. From a clinical perspective, a renewed focus on training/education and standardization of assessment is required. PMID- 26564212 TI - Remnant-preserving and re-tensioning technique to cover the graft in anterior cruciate ligament reconstruction. AB - PURPOSE: This study set out to assess the clinical and radiographic outcomes and the extent of synovial coverage on second-look arthroscopy of anterior cruciate ligament (ACL) reconstruction using a remnant-preserving and re-tensioning technique to easily cover the graft with a remnant. METHODS: Forty-three subjects with ACL rupture underwent remnant-preserving and re-tensioning ACL reconstruction using a free tendon Achilles allograft between 2011 and 2013. The clinical outcomes were assessed by Lysholm knee score, Lachman stress test, pivot shift test, International Knee Documentation Committee (IKDC) classification, and Tegner Activity Scale score. Side-to-side difference (SSD) was assessed on stress radiographs. The extent of synovialization was evaluated on second-look arthroscopy. RESULTS: The mean Lysholm score was 54 +/- 11 before surgery and 94 +/- 5 at the last follow-up (p < 0.001). On Lachman stress test, 42 subjects had grade 0 or 1 on the Lachman stress test, and 42 had grade 0 or 1 on the pivot shift test. Forty-one subjects had IKDC classification A or B; two were classified as C or D. The median Tegner Activity Scale score was 6.5 (range 5-9) before injury and 6 (range 4-8) at the last follow-up (p = 0.048). Mean SSD on stress radiographs was 9.9 +/- 2.6 mm preoperatively and 1.0 +/- 1.7 mm at the last follow-up (p < 0.001). In the assessment of the extent of synovial coverage of the graft, 39 subjects were in group 1 (>75 %) for synovial coverage of the graft, three were in group 2 (50-75 %), and one was in group 4 (<=25 %). CONCLUSIONS: The remnant-preserving and re-tensioning technique resulted in satisfying short-term results clinically and radiologically and good synovial coverage on second-look arthroscopy. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 26564213 TI - Collagen application reduces complication rates of mid-substance ACL tears treated with dynamic intraligamentary stabilization. AB - PURPOSE: Dynamic intraligamentary stabilization was recently proposed as an option for the treatment of acute ACL ruptures. The aim of this study was to investigate the feasibility of the procedure in mid-substance ACL ruptures and examine whether the additional application of a bilayer collagen I/III membrane would provide for a superior outcome. METHODS: The study group consisted of patients presenting with a mid-substance ACL rupture undergoing dynamic intraligamentary stabilization using the LigamysTM device along with application of a collagen I/III membrane to the surface of the ACL (group A, n = 23). The control group comprised a matched series of patients presenting with a mid substance ACL rupture also treated by dynamic intraligamentary stabilization LigamysTM repair, however, without additional collagen application (group B, n = 33). Patients were evaluated preoperatively and at 24-month follow-up for stability as well as Tegner and Lysholm scores. Knee laxity was measured as a difference in anterior translation (DeltaAP) and pivot shift. Any events occurring during the follow-up period of 24 months were documented. Logistic regression of complications was performed, and adjustment undertaken where necessary. RESULTS: A high total complication rate of 78.8 % was noted in group B, compared to group A (8.7 %) (p = 0.002). The addition of a collagen membrane was the only independent prognostic factor associated with reduced complications (OR 8.0, CI 2.0-32.2, p = 0.003, for collagen-free treatment). In group B, 6 patients suffered a re-rupture with subsequent instability requiring secondary hamstring reconstruction surgery, and 11 developed extension loss requiring arthroscopic debridement, whilst in group A, 2 patients required arthroscopic debridement for loss of exension, with no further encountered complication. Median Lysholm score was significantly higher in group A compared to group B (median 100 range 93-100 vs median 95 range 60-100, p = 0.03) at final follow-up. CONCLUSIONS: A high complication rate following ACL LigamysTM repair of mid substance ruptures was noted. Application of a collagen membrane to the surface of the ACL resulted in a reduced incidence of extension deficit and re-ruptures. The results indicate that solitary ACL LigamysTM repair does not present an appropriate treatment modality for mid-substance ACL ruptures. Collage application proved to provide healing benefits with superior clinical outcome after ACL repair. LEVEL OF EVIDENCE: Case control study, Level III. PMID- 26564214 TI - The influence of suprapectoral arthroscopic biceps tenodesis for isolated biceps lesions on elbow flexion force and clinical outcomes. AB - PURPOSE: To prospectively evaluate elbow flexion force, cosmetic and clinical outcome of all-arthroscopic suprapectoral biceps tenodesis for isolated biceps lesions. METHODS: Tenodesis was performed using a 6.25-mm absorbable interference screw for intraosseous fixation. Seventeen out of 24 patients (70.8 %, median age 49.0 +/- 10.1 years; 10 = male) could be included for 24 months follow-up. Elbow flexion strength in 10 degrees and 90 degrees elbow flexion, the upward directed force of the upper arm in the O'Brien position, objective evaluation of a Popeye-sign deformity and validated clinical scores (CMS, SST, ASES) were assessed preoperatively, 3, 6, 12 and 24 months postoperatively. RESULTS: Elbow flexion strength in 90 degrees improved significantly from 12 months onwards (P = 0.001) without significant difference to the contralateral arm from 3 months postoperatively (n.s.). At 24 months, an average increase of 46.4 % (median 37.7 %) from preoperative could be seen. The dominant arm was affected in 70.6 %. All scores showed a significant improvement 3 months postoperatively: SST (P = 0.003), ASES (P = 0.006) and total CMS (P < 0.001). Three patients (17.6 %) developed a distalization of the maximum biceps circumference of more than 20 % compared to preoperative. CONCLUSIONS: All-arthroscopic proximal suprapectoral intraosseous single-limb biceps tenodesis for the treatment of isolated biceps lesions provides good-to-excellent clinical results with significant improvement of elbow flexion strength and clinical scores and no significant difference to the unaffected contralateral arm. LEVEL OF EVIDENCE: IV. PMID- 26564215 TI - Similar results comparing early and late surgery in open repair of traumatic rotator cuff tears. AB - PURPOSE: The purpose was to investigate whether surgical repair earlier or later than 3 months after injury may result in similar outcomes and patient satisfaction. METHODS: Seventy-three patients (75 shoulders, 58 males, mean age 59) who had undergone surgical intervention for traumatic rotator cuff tears from 1999 to 2011 were assessed by MRI, clinical examination and Western Ontario Rotator Cuff Index (WORC) as a primary outcome measure and Oxford Shoulder score (OSS), Constant-Murley score (CS) and EQ-5D as secondary. The patients treated less than 3 months after injury (n = 39) were compared with patients treated more than 3 months after injury (n = 36). The average follow-up time was 56 months (range 14-149), and the average time from injury to repair for all patients was 16 weeks (range 3-104). A single senior radiologist performed a blinded evaluation of all the MRIs. Rotator cuff integrity, presence of arthritis, fatty degeneration and muscle atrophy were evaluated. RESULTS: No differences were found for any of the assessed outcomes (WORC, OSS, CS and EQ-5D) between the two groups. The mean WORC % was 77 % for both groups. Re-tear frequency was 24 %, nine in both groups. Patients with re-tear reported less satisfaction with their outcome. CONCLUSIONS: The surgical treatment of symptomatic traumatic rotator cuff tears repairable later than 3 months after injury yields a good functional outcome, a high level of subjective patient satisfaction, and at the same level for patients receiving earlier treatment. Based on our findings, surgical repair could be encouraged whenever technically possible. LEVEL OF EVIDENCE: Retrospective Comparative Study, Level III. PMID- 26564216 TI - Posterior vaginal compartment repairs: Where are the main anatomical defects? AB - INTRODUCTION AND HYPOTHESIS: Traditionally, it has been believed that posterior vaginal compartment prolapse was largely due to defects in the rectovaginal fascia, with surgical repairs concentrating on addressing this defect. We aimed to determine the relative size of defects at the different vaginal levels (I-III) following a large number of posterior vaginal compartment repairs (PRs) to determine whether this traditional viewpoint is still appropriate. METHODS: In a cross-sectional study of 300 consecutive PRs, mostly following prior or concomitant hysterectomy, two sets of markers of posterior compartment prolapse were used to measure anatomical defects at levels I-III: (i) from Pelvic Organ Prolapse Quantification (POP-Q) system points C, Ap, Bp, and genital hiatus (GH), and from Posterior Repair Quantification (PR-Q) perineal gap (PG), posterior vaginal-vault descent (PVVD), midvaginal laxity (MVL)-vault undisplaced, and rectovaginal fascial laxity (RVFL). RESULTS: The largest defects were found at level I (PVVD: mean 6.0 cm; point C, mean minus 0.9 cm), and level III (PG, mean 2.9 cm; GH, mean 3.7 cm). Level II defects (MVL-vault undisplaced, mean 1.3 cm; RVFL, mean 1.1 cm; points Ap, Bp, both mean 1.0 cm) were relatively small. CONCLUSIONS: This study suggests that the defects found at surgery for posterior vaginal compartment prolapse were more frequent at the vaginal vault (level I) and vaginal introitus (level III) than at midvagina (level II). These findings should have implications for surgical planning. PMID- 26564217 TI - Sacrocolpopexy: is there a consistent surgical technique? AB - INTRODUCTION: Sacrocolpopexy is the gold standard treatment for vault prolapse. Current reported standards regarding surgical approach and technique vary. Our aim was to evaluate the surgical techniques used and identify any consistency. METHODS: Electronic surveys were sent to 148 candidates enrolled in a sacrocolpopexy workshop at the 2012 American Urogynecologic Society (AUGS) annual meeting and as a link in the International Urogynecology Association (IUGA) e magazine. The survey assessed demographics, specific surgical steps including dissection techniques, number and type of sutures, graft materials, and the approach to intraoperative complications. RESULTS: Within the AUGS group, 61 candidates responded (41 %). From the IUGA membership, 128 responded for a total of 189. Overall, 59 % identified their primary practice as urogynaecology, 43 % having completed a fellowship. Only 33 % reported performing sacrocolpopexy as the primary surgery for vault prolapse. Technical aspects: 99.4 % used polypropylene mesh, with 57 % attaching it to the vagina using non-absorbable monofilament sutures. An average of 3-4 sutures were used on the anterior and posterior walls respectively. Suture location: 22.5 % reported not placing apical sutures and 55.7 % place their anterior wall sutures midway down the vagina. Posteriorly, 47 (30 %) placed sutures through the uterosacral ligaments, 19 (12.4 %) through the levator ani and 15 % extend the mesh to the perineal body. The mesh was attached to the sacrum using permanent sutures by 75 %. Dissection of the sacrum was deemed the most technically difficult aspect. CONCLUSION: Surgical technique varies widely despite the level of expertise and training. This study highlights the need for an evaluation of the effect of surgical technique on outcomes. PMID- 26564218 TI - Response to the letter to the editor: the correct episiotomy--does it exist? PMID- 26564219 TI - The correct episiotomy: Does it exist? PMID- 26564220 TI - A novel insight into the treatment of an intravesical eroded mesh: endoscopic assisted cystoscopic approach. PMID- 26564221 TI - Age at hysterectomy as a predictor for subsequent pelvic organ prolapse repair. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate the association between patient age at the time of hysterectomy and subsequent pelvic organ prolapse (POP) surgery. METHODS: We gathered data on all benign hysterectomies and POP surgeries performed in Denmark on Danish women from 1977 to 2009 from the Danish National Patient Registry. The cohort consisted of 154,882 hysterectomized women, who were followed up for up to 32 years. Survival analysis for each age group at hysterectomy was performed using Kaplan-Meier product limit methods. RESULTS: For all hysterectomized women, we found that low age at hysterectomy yielded a lower risk of subsequent POP surgery than did hysterectomy at an older age. This difference diminished after stratification by indication; all non-POP hysterectomies had a low cumulative incidence at 8-11 % at the end of the follow-up period. For all women hysterectomized, the predominant compartment for POP surgery was the posterior. Women hysterectomized when aged over 66 years had a higher proportion of POP surgery in the apical compartment than in the other age groups (p = 0.000). CONCLUSION: Our findings indicate that age at hysterectomy only marginally influences the risk of subsequent POP surgery for women hysterectomized for indications other than POP. If POP is the indication for hysterectomy, the risk of undergoing subsequent POP surgery increases substantially. PMID- 26564222 TI - Surgical management of urethral diverticula in women: a systematic review. AB - Urethral diverticula (UD) are pouch-like outgrowths of the urethral lumen and surgery is by far the most common approach in symptomatic patients. The aim of this systematic review was to evaluate surgical techniques and outcomes in adult women with urethral diverticula. Our secondary objective was to determine the types of study designs. A systematic review of the literature was conducted. Medline, Cinahl and Embase were used as data sources. One hundred and eight studies, including 1,947 patients, remained for final analysis. We summarised 40 single case reports and 68 case series. Overall, transvaginal resection of the UD +/- reconstruction was performed in the majority of patients (84 %), followed by marsupialisation (3.8 %) and transurethral endoscopic unroofing (2.0 %). Various other surgical techniques were reported in 181 out of 1,858 cases (9.7 %). Nineteen studies, dealing with 584 patients in all, evaluated a combination of vaginal diverticulectomy with an additional surgical procedure. Fifty-six out of 108 studies (52 %) documented the resolution of symptoms, describing 717 out of 1,044 patients in all being completely symptom-free after surgery. Only 50 out of 108 studies (46.2 %) provided detailed information on the length of follow-up, but showed a poor reporting standard regarding prognosis. Complications were studied only selectively. Because of the inconsistency of these data, it was impossible to analyse them collectively. There were no comparative studies on the different types of surgery in women with urethral diverticula. Overall, the non comparative nature of the current evidence on the surgical management of UD does not allow any accurate estimation of success and complication rates. PMID- 26564223 TI - Validation of the Polish version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire. AB - INTRODUCTION AND HYPOTHESIS: The aim of the study was to develop a Polish version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ) to evaluate sexual function in patients with stress urinary incontinence (SUI) and pelvic organ prolapse (POP) versus a control group. METHODS: Before the validation study, a pilot study of the Polish version of the PISQ was performed in 22 women with pelvic floor dysfunctions. The respondents completed the questionnaire at recruitment and 2 weeks later. Test-retest reliability and internal consistency were determined. The validation study was performed in 249 sexually active women (123 with urodynamic SUI and POP; 126 healthy controls). The study group reported urinary incontinence (UI) at the urogynecological ambulatory clinic, where they underwent urogynecological and urodynamic examinations. All participants completed the questionnaire. PISQ results from both groups were compared and correlated with those of the King's Health Questionnaire (KHQ) and patient age. RESULTS: Test-retest reliability was good according to Pearson's correlation coefficient (r = 0.89, p < 0.001). PISQ had high internal consistency (Cronbach's alpha = 0.878). The total PISQ score was significantly lower in the study group compared with the controls (83.6 +/- 14.9 vs 95.7 +/- 10.3, p < 0.001), as were scores for individual domains: Behavioral/Emotive, Physical, Partner-Related (33.9 +/- 10.2 vs 39.8 +/- 7.8, 31.7 +/- 6.9 vs 37.1 +/- 2.8, and 18.0 +/- 3.1 vs 19.4 +/- 2.6 respectively; p < 0.001), confirming the lower quality of sexual function in women with SUI and POP. A correlation between PISQ and KHQ scores and patient age was confirmed. CONCLUSIONS: The Polish version of the PISQ is a reliable tool for evaluating sexual function in women with POP and UI. PMID- 26564224 TI - Effect of norfloxacin therapy for acute, uncomplicated lower urinary tract infection on vaginal Candida prevalence. AB - INTRODUCTION AND HYPOTHESIS: Acute uncomplicated lower urinary tract infections (UTI) and vulvovaginal candidiasis (VVC) both occur frequently in women. Although VVC is believed to commonly occur after antibiotic therapy, few studies have demonstrated this association. Thus, the aim of the study was to estimate the prevalence of colonization by Candida spp. and VVC after norfloxacin (NOR) use for UTI and the effects on the vaginal microbiota and inflammatory process. METHODS: This was a prospective cohort study of women with culture-proven UTI who were treated with NOR (antibiotic group). The control group consisted of women with noninfectious diseases or in preventive care. Candida vaginal infections were monitored both clinically and mycologically at baseline and at the follow-up evaluation. RESULTS: All women showed UTI remission after NOR treatment, and no woman in either group, antibiotic and control, showed symptoms of VVC. Both groups showed similar ratios of a positive Candida culture at baseline (6.7 % and 12.8 %, respectively) and at follow-up (3.3 % and 8.5 %, respectively) (p = 0.2768 and p = 0.5035, respectively). The antibiotic group showed no increased risk of Candida colonization or VVC after NOR treatment compared with the control group [odds ratio (OR) 0.556, 95 % confidence interval (CI) 0.2407-10.05]. CONCLUSIONS: NOR was effective for UTI treatment, did not increase the risk of vaginal colonization by Candida or VVC, and did not lead to major disturbances of the vaginal microbiota. PMID- 26564225 TI - Association of osteoporosis with genetic variants of circadian genes in Chinese geriatrics. AB - This study was designed to investigate the association of circadian gene single nucleotide polymorphisms (SNPs) with the risk of osteoporosis. We found that the rs3781638 GG genotype was positively associated with osteoporosis prevalence in females, whereas the rs2292910 AC genotype was negatively associated with osteoporosis prevalence in a geriatric cohort. INTRODUCTION: Studies have shown that disruption of endogenous circadian rhythms may increase the risk of developing type II diabetes and obesity, which are reportedly associated with osteoporosis (OP). Thus, abnormalities of circadian genes may indirectly induce OP. Here, we investigated the association of OP with 14 SNPs located in seven circadian genes. METHODS: The research subjects, geriatric residents of Shanghai Minhang, China, diagnosed with OP (N = 171) or osteopenia (N = 226) or without specific diseases (N = 200), were genotyped for 14 genetic variants of circadian genes by competitive allele-specific polymerase chain reaction. The prevalence of polymorphisms among the subject groups and the association between the SNPs and osteoporosis were investigated. RESULTS: Among the 14 genotyped SNPs, we found an association between the CRY2 gene rs2292910 SNP and osteoporosis (r = -0.082, p = 0.045) in the geriatric cohort. We found a decreased risk between cryptochrome 2 rs2292910 and OP (A/C odds ratio = 0.647, p = 0.044) but an increased risk between MTNR1B rs3781638 and OP (G/G odds ratio = 2.058, p = 0.044). CONCLUSION: For the first time, we show that Cry 2 rs2292910 and MTNR1B rs3781638 are associated with osteoporosis in a Chinese geriatric cohort. Therefore, targeting the abnormalities of the CRY2 and MTNR1B genes may be a potential strategy to treat and/or to prevent osteoporosis. PMID- 26564226 TI - The real enemy is fragility fracture, not osteoporosis. PMID- 26564227 TI - A BMD threshold for treatment efficacy in osteoporosis? A need to consider the whole evidence base. PMID- 26564228 TI - Using self-reports of pain and other variables to distinguish between older women with back pain due to vertebral fractures and those with back pain due to degenerative changes. AB - Women with back pain and vertebral fractures describe different pain experiences than women without vertebral fractures, particularly a shorter duration of back pain, crushing pain and pain that improves on lying down. This suggests a questionnaire could be developed to identify older women who may have osteoporotic vertebral fractures. INTRODUCTION: Approximately 12 % of postmenopausal women have vertebral fractures (VFs), but less than a third come to clinical attention. Distinguishing back pain likely to relate to VF from other types of back pain may ensure appropriate diagnostic radiographs, leading to treatment initiation. This study investigated whether characteristics of back pain in women with VF are different from those in women with no VFs. METHODS: A case control study was undertaken with women aged >=60 years who had undergone thoracic spinal radiograph in the previous 3 months. Cases were defined as those with VFs identified using the algorithm-based qualitative (ABQ) method. Six hundred eighty-three potential participants were approached. Data were collected by self-completed questionnaire including the McGill Pain Questionnaire. Chi squared tests assessed univariable associations; logistic regression identified independent predictors of VFs. Receiver operating characteristic (ROC) curves were used to evaluate the ability of the combined independent predictors to differentiate between women with and without VFs via area under the curve (AUC) statistics. RESULTS: One hundred ninety-seven women participated: 64 cases and 133 controls. Radiographs of controls were more likely to show moderate/severe degenerative change than cases (54.1 vs 29.7 %, P = 0.011). Independent predictors of VF were older age, history of previous fracture, shorter duration of back pain, pain described as crushing, pain improving on lying down and pain not spreading down the legs. AUC for combination of these factors was 0.85 (95 % CI 0.79 to 0.92). CONCLUSION: We present the first evidence that back pain experienced by women with osteoporotic VF is different to back pain related solely to degenerative change. PMID- 26564229 TI - Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells. AB - Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFkappaB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFkappaB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-beta and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFkappaB, which orchestrates all these mechanisms. PMID- 26564231 TI - [The blindness of Antonio Maria Esquivel y Suarez de Urbina]. PMID- 26564230 TI - DNA damage response in cisplatin-induced nephrotoxicity. AB - Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) are an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy. PMID- 26564232 TI - Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats. AB - RATIONALE: Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USVs) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USVs in response to amphetamine is not determined. OBJECTIVES: The aim of the present study was to determine if individual differences in NSS and USVs can predict locomotor and USV response to amphetamine (0.0, 0.3, and 1.0 mg/kg) after acute and chronic exposure. METHODS: Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for seven exposures, and USVs and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. RESULTS: Regression analyses indicated that amphetamine dose dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency-modulated (FM) USVs, but the strength of prediction depended on IEN response. CONCLUSIONS: Results provide evidence that locomotor activity and FM USVs induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USVs by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine-measured by FM USVs-depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster. PMID- 26564234 TI - Contributions to drug abuse research of Steven R. Goldberg's behavioral analysis of stimulus-stimulus contingencies. AB - By the mid-1960s, the concept that drugs can function as reinforcing stimuli through response-reinforcer contingencies had created a paradigm shift in drug abuse science. Steve Goldberg's first several publications focused instead on stimulus-stimulus contingencies (respondent conditioning) in examining Abraham Wikler's two-factor hypothesis of relapse involving conditioned withdrawal and reinforcing effects of drugs. Goldberg provided a compelling demonstration that histories of contingencies among stimuli could produce lasting withdrawal reactions in primates formerly dependent on opioids. Other studies conducted by Goldberg extended the analysis of effects of stimulus-stimulus contingencies on behavior maintained by opioid reinforcing effects and showed that withdrawal inducing antagonist administration can produce conditioned increases in self administration. Subsequent studies of the effects of stimuli associated with cocaine injection under second-order schedules showed that the maintenance of behavior with drug injections was in most important aspects similar to the maintenance of behavior with more conventional reinforcers when the behavior disrupting pharmacological effects of the drugs were minimized. Studies on second order schedules demonstrated a wide array of conditions under which behavior could be maintained by drug injection and further influenced by stimulus-stimulus contingencies. These schedules present opportunities to produce in the laboratory complex situations involving response- and stimulus-stimulus contingencies, which go beyond simplistic pairings of stimuli and more closely approximate those found with human drug abusers. A focus on the response- and stimulus-stimulus contingencies, and resulting quantifiable changes in objective and quantifiable behavioral endpoints exemplified by the studies by Steve Goldberg, remains the most promising way forward for studying problems of drug dependence. PMID- 26564233 TI - Activation of adenosine A2A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation. AB - RATIONALE: Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to pleasurable stimuli, and these USVs are considered a tool for investigating reward and motivation. OBJECTIVES: This study aimed to clarify how activity of adenosine A2A receptors, which modulate reward and motivation, influences 50-kHz USV emission in rats. METHODS: Rats received one of the following treatments in a test cage: (1) acute administration of the A2A receptor agonist CGS 21680 (0.05 0.2 mg/kg, i.p.) during social interactions; (2) long-term amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.) administration on alternate days, alone or with CGS 21680, followed after 7 days of discontinuation by test cage re exposure, to assess drug-conditioning effects, and thereafter drug challenge; (3) acute administration of the D1/D2 receptor agonist apomorphine (4 mg/kg, i.p.), alone or with CGS 21680; and (4) long-term administration of the non-selective A1/A2A receptor antagonist caffeine (15 mg/kg, i.p.), on alternate days. USVs and locomotor activity were evaluated throughout the treatments. RESULTS: CGS 21680 attenuated 50-kHz USV emission stimulated by social interactions, amphetamine, apomorphine, and morphine, and rats administered CGS 21680 with amphetamine or morphine emitted fewer conditioned 50-kHz USVs upon test cage re-exposure, compared with rats administered amphetamine or morphine alone. Moreover, CGS 21680 administration prevented long-term changes in locomotor activity in amphetamine- and morphine-treated rats. Finally, caffeine had no effect on 50-kHz USVs. CONCLUSIONS: These results indicate that activation of A2A receptors attenuates 50-kHz USV emission in rats and further elucidate how these receptors modulate the motivational properties of natural and pharmacological stimuli. PMID- 26564235 TI - Local structure based method for prediction of the biochemical function of proteins: Applications to glycoside hydrolases. AB - Thousands of protein structures of unknown or uncertain function have been reported as a result of high-throughput structure determination techniques developed by Structural Genomics (SG) projects. However, many of the putative functional assignments of these SG proteins in the Protein Data Bank (PDB) are incorrect. While high-throughput biochemical screening techniques have provided valuable functional information for limited sets of SG proteins, the biochemical functions for most SG proteins are still unknown or uncertain. Therefore, computational methods for the reliable prediction of protein function from structure can add tremendous value to the existing SG data. In this article, we show how computational methods may be used to predict the function of SG proteins, using examples from the six-hairpin glycosidase (6-HG) and the concanavalin A-like lectin/glucanase (CAL/G) superfamilies. Using a set of predicted functional residues, obtained from computed electrostatic and chemical properties for each protein structure, it is shown that these superfamilies may be sorted into functional families according to biochemical function. Within these superfamilies, a total of 18 SG proteins were analyzed according to their predicted, local functional sites: 13 from the 6-HG superfamily, five from the CAL/G superfamily. Within the 6-HG superfamily, an uncharacterized protein BACOVA_03626 from Bacteroides ovatus (PDB 3ON6) and a hypothetical protein BT3781 from Bacteroides thetaiotaomicron (PDB 2P0V) are shown to have very strong active site matches with exo-alpha-1,6-mannosidases, thus likely possessing this function. Also in this superfamily, it is shown that protein BH0842, a putative glycoside hydrolase from Bacillus halodurans (PDB 2RDY), has a predicted active site that matches well with a known alpha-L-galactosidase. In the CAL/G superfamily, an uncharacterized glycosyl hydrolase family 16 protein from Mycobacterium smegmatis (PDB 3RQ0) is shown to have local structural similarity at the predicted active site with the known members of the GH16 family, with the closest match to the endoglucanase subfamily. The method discussed herein can predict whether an SG protein is correctly or incorrectly annotated and can sometimes provide a reliable functional annotation. Examples of application of the method across folds, comparing active sites between two proteins of different structural folds, are also given. PMID- 26564236 TI - Simultaneous multicolor detection of RNA and proteins using super-resolution microscopy. AB - A number of non-membranous cellular bodies have been identified in higher eukaryotes, and these bodies contain a specific set of proteins and RNAs that are used to fulfill their functions. The size of these RNA-containing cellular bodies is usually on a submicron scale, making it difficult to observe fine structures using optical microscopy due to the diffraction limitation of visible light. Recently, microscope companies have released super-resolution microscopes that were developed using different principles, enabling the observation of sub-micron structures not resolvable in conventional fluorescent microscopy. Here, we describe multi-color fluorescent in situ hybridization techniques optimized for the simultaneous detection of RNA and proteins using super-resolution microscopy, namely structured illumination microscopy (SIM). PMID- 26564237 TI - Super-resolution measurement of distance between transcription sites using RNA FISH with intronic probes. AB - Nascent transcripts being copied from specific human genes can be detected using RNA FISH (fluorescence in situ hybridization) with intronic probes, and the distance between two different nascent transcripts is often measured when studying structure-function relationships. Such distance measurements are limited by the resolution of the light microscope. Here we describe methods for measuring these distances in cultured cells with a precision of a few tens of nanometers, using equipment found in most laboratories (i.e., a wide-field fluorescence microscope equipped with a charged-coupled-device camera). Using images of pairs of transcripts that are often co-transcribed, we discuss how selection of cell type, design of FISH probes, image acquisition, and image processing affect the precision that can be achieved. PMID- 26564238 TI - Quantitative gene expression analysis in Caenorhabditis elegans using single molecule RNA FISH. AB - Advances in fluorescent probe design and synthesis have allowed the uniform in situ labeling of individual RNA molecules. In a technique referred to as single molecule RNA FISH (smRNA FISH), the labeled RNA molecules can be imaged as diffraction-limited spots and counted using image analysis algorithms. Single RNA counting has provided valuable insights into the process of gene regulation. This microscopy-based method has often revealed a high cell-to-cell variability in expression levels, which has in turn led to a growing interest in investigating the biological significance of gene expression noise. Here we describe the application of the smRNA FISH technique to samples of Caenorhabditis elegans, a well-characterized model organism. PMID- 26564240 TI - The issue of consent in medical practice. AB - Following a recent court judgment, legal and moral issues surrounding consent have been thrown into the spotlight. Elizabeth Larner, Solicitor, and Rachel Carter, Partner, of Wollen Michelmore LLP, look at the issues surrounding consent, including where problems arise in the fields of clinical negligence and non-accidental injury and what health care professionals can do to ensure that their advice to a patient about a procedure or treatment is sufficiently cogent and appropriately recorded so as to avoid later criticism and possible legal action. This annotation gives an overview of the legal principles surrounding consent in medical practice including informed consent, refusal of treatment and issues of capacity. PMID- 26564239 TI - Impact of 14-day bed rest on serum adipokines and low-grade inflammation in younger and older adults. AB - Ageing and inactivity both contribute to systemic inflammation, but the effects of inactivity on inflammation in healthy elderly individuals have not been elucidated. We hypothesised that 14-day bed rest could affect the pro- and anti inflammatory markers in young subjects differently than in older adults. A short term 14-day horizontal bed rest study (BR14) has been used as a model of inactivity in two groups of healthy male volunteers: 7 aged 18-30 years (young) and 16 aged 55-65 years (older adults). The effects of inactivity on inflammation were compared. Key low-grade inflammation mediators, tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), visfatin, resistin, and anti-inflammatory adiponectin were measured in fasting serum samples, collected at baseline (BDC) and post BR14. Young responded to BR14 by increasing serum visfatin and resistin while older adults responded to BR14 by increasing IL-6 and TNF-alpha. In addition, serum adiponectin increased in all participants. Data from correlation analysis demonstrated positive association between Delta serum visfatin and Delta IL-6 in both groups, while Delta serum adiponectin was negatively associated with Delta TNF-alpha in young and positively associated with Delta resistin in the older adults. As little as 14 days of complete physical inactivity (BR14) negatively affected markers of low-grade inflammation in both groups, but the inflammation after BR14 was more pronounced in older adults. The effect of BR14 on IL-6 and resistin differed between young and older adults. Inflammatory responses to BR14 in older adults differed from those reported in the literature for obese or subjects in pathological states, suggesting potentially different mechanisms between inactivity- and obesity-induced inflammations. PMID- 26564241 TI - A novel violet/blue light-emitting device based on Ce2Si2O7. AB - Rare-earth silicates are highly efficient materials for silicon-based light sources. Here we report a novel light-emitting device based on Ce2Si2O7. Intense violet/blue electroluminescence was observed, with a turn-on voltage of about 13 V. The violet/blue emission is attributed to 4f-5d transitions of the Ce(3+) ions in Ce2Si2O7, which are formed by interfacial reaction of CeO2 and Si. Electroluminescence and photoluminescence mechanisms of the Ce2Si2O7 light emitting device are also discussed. PMID- 26564242 TI - Computerized System for Staging Peritoneal Surface Malignancies. AB - BACKGROUND: Peritoneal surface malignancies (PSMs) are usually staged using Sugarbaker's Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC-s). Although these staging tools are essential for selecting patients and evaluating outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), both scoring models lack some anatomic information, thus making staging laborious and unreliable. Maintaining Sugarbaker's original concepts, we therefore developed a computerized digital tool, including a new anatomic scheme for calculating PCI and CC-s corresponding closely to patients' real anatomy. Our new anatomic model belongs in a web-based application known as the PSM Staging System, which contains essential clinical and pathological data for the various PSMs currently treated. METHODS: The new digital tool for staging PSM runs on a personal computer or tablet and comprises male and female colored anatomic models for the 13 endoabdominal regions, with borders defined according to real anatomic landmarks. A drag-and-drop tool allows users to compute the PCI and CC-s, making it easier to localize and quantify disease at diagnosis and throughout treatment, and residual disease after CRS. CONCLUSIONS: Once tested online by registered users, our computerized application should provide a modern, shareable, comprehensive, user-friendly PSM staging system. Its anatomic features, along with the drag-and-drop tool, promise to make it easier to compare preoperative and postoperative PCIs, thus improving the criteria for selecting patients to undergo CRS plus HIPEC. By specifying the size, site, and number of residual lesions after CRS plus HIPEC, our digital tool should help stratify patients into outcome classes. PMID- 26564243 TI - Long-Term Survival in Patients with Gastroesophageal Junction Cancer Treated with Preoperative Therapy: Do Thoracic and Abdominal Approaches Differ? AB - BACKGROUND: The optimal surgical approach for gastroesophageal junction (GEJ) cancer treated with preoperative therapy remains controversial. We compared the outcomes of patients who underwent either esophagectomy or gastrectomy and identified variables associated with overall survival (OS). METHODS: We reviewed records of patients with Siewert types II and III GEJ adenocarcinoma who were treated with preoperative therapy followed by resection from 1995 to 2013. OS was assessed using Kaplan-Meier curves and associated variables were analyzed using Cox proportional hazards models. RESULTS: Of 143 patients, 110 (76.9 %) had type II and 33 (23.1 %) had type III tumors. Most (86 %) patients had stage T3 or T4 disease, and more than half had N+ (62 %) disease. The majority (93 %) received neoadjuvant chemoradiation; 7 % received chemotherapy alone. Patients with type II tumors underwent either esophagectomy (75 %) or gastrectomy (25 %). Patients with type III tumors primarily underwent gastrectomy (88 %). Eighty-six (60 %) patients underwent extended (D1+/D2) abdominal lymphadenectomy. We saw no differences between esophagectomy and gastrectomy patients in R0 resection rate (94 vs. 95 %; p = 0.9), number of nodes removed (mean, 18.3 vs. 19.3; p = 0.6), or 60-day mortality rate (4 vs. 4 %; p = 1.0). The median follow-up period for survivors was 65 months. Esophagectomy and gastrectomy showed similar 5-year OS rates (49 vs. 53 %; p = 0.8). Surgical approach was not associated with OS [hazard ratio (HR) 1.30; 95 % confidence interval (CI) 0.68-2.45; p = 0.43]. The strongest predictor of OS was extended lymphadenectomy (HR 0.55; 95 % CI, 0.32 0.94; p = 0.03). CONCLUSIONS: R0 resection and OS rates were similar in patients undergoing esophagectomy or gastrectomy after neoadjuvant therapy; however, extended abdominal lymphadenectomy may improve OS rates. PMID- 26564244 TI - A High RORgammaT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells). AB - BACKGROUND: Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. METHODS: The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. RESULTS: A high RORgammaT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORgammaT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). CONCLUSIONS: This study confirmed a high RORgammaT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC. PMID- 26564245 TI - On the power of autobiographical memories: from threat and challenge appraisals to actual behaviour. AB - Autobiographical memories are a major feature of mental life in humans. However, research on the influence of autobiographical recall on actual behaviour is scarce. We predicted and found that general memories of failure and specific memories of success resulted in worse performance than general memories of success and specific memories of failure. This performance pattern was mediated by task appraisal, suggesting that autobiographical memories (of failure and success) impact performance by shaping the perception of the upcoming task. Combined with the fact that these effects occurred even when the content of autobiographical memories was unrelated to the upcoming task, the present research represents an important step forward in understanding how autobiographical recall influences actual behaviour. PMID- 26564246 TI - Serum retinol in post-partum mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency is absent. AB - Serum retinol was assessed in mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency known to be absent. Paired cord and maternal blood (n = 201) were collected after delivery and analysed for serum retinol and C-reactive protein (CRP). Liver intake during pregnancy and intention to breastfeed were also assessed. Mean serum retinol was 1.03 umol/L +/- 0.40 in mothers and 0.73 +/- 0.24 umol/L in newborns, with 21.4% and 49.3% having serum retinol <0.70 umol/L (<20 ug/dL), respectively. Raised CRP was found in 59.9% of mothers, with a significant negative correlation between serum retinol and CRP (r = -0.273; p < 0.0001). Liver was eaten by 87.6% of mothers, and 99% indicated their intention to breastfeed. Despite consumption of liver, serum retinol was low in both the mother and the newborn. The conventional cut-off for serum retinol, i.e. <0.70 umol/L may therefore not apply for the mother and newborn in the period immediately after delivery. Serum retinol may be influenced by factors other than vitamin A status, e.g. the haemodilution of pregnancy, as well as the acute phase response induced by the birth process, as suggested by raised CRP in 60% of mothers. In the newborns, the low serum retinol is likely to increase rapidly, as liver is frequently eaten by mothers and practically all of them intended to breastfeed. Our results confirm the need for better indicators of vitamin A status or alternative cut-off values during this period. PMID- 26564247 TI - Structures, Not Strings: Linguistics as Part of the Cognitive Sciences. AB - There are many questions one can ask about human language: its distinctive properties, neural representation, characteristic uses including use in communicative contexts, variation, growth in the individual, and origin. Every such inquiry is guided by some concept of what 'language' is. Sharpening the core question--what is language?--and paying close attention to the basic property of the language faculty and its biological foundations makes it clear how linguistics is firmly positioned within the cognitive sciences. Here we will show how recent developments in generative grammar, taking language as a computational cognitive mechanism seriously, allow us to address issues left unexplained in the increasingly popular surface-oriented approaches to language. PMID- 26564248 TI - The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model. AB - Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the 'social regulatory cycle', specifies at multiple levels of description the act of regulating another person's emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. PMID- 26564249 TI - Optimally conductive networks in randomly dispersed CNT:graphene hybrids. AB - A predictive model is proposed that quantitatively describes the synergistic behavior of the electrical conductivities of CNTs and graphene in CNT:graphene hybrids. The number of CNT-to-CNT, graphene-to-graphene, and graphene-to-CNT contacts is calculated assuming a random distribution of CNTs and graphene particles in the hybrids and using an orientation density function. Calculations reveal that the total number of contacts reaches a maximum at a specific composition and depends on the particle sizes of the graphene and CNTs. The hybrids, prepared using inkjet printing, are distinguished by higher electrical conductivities than that of 100% CNT or graphene at certain composition ratios. These experimental results provide strong evidence that this approach involving constituent element contacts is suitable for investigating the properties of particulate hybrid materials. PMID- 26564250 TI - Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media. AB - Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been evaluated for the treatment of immunological diseases. However, the animal derived growth supplements utilized for MSC manufacturing may lead to clinical complications. Characterization of alternative media formulations is imperative for MSC therapeutic application. Human BMMSC and AdMSC were expanded in media supplemented with either human platelet lysates (HPL), serum-free media/xeno-free FDA-approved culture medium (SFM/XF), or fetal bovine serum (FBS) and the effects on their properties were investigated. The immunophenotype of resting and IFN gamma primed BMMSC and AdMSC remained unaltered in all media. Both HPL and SFM/XF increased the proliferation of BMMSC and AdMSC. Expansion of BMMSC and AdMSC in HPL increased their differentiation, compared to SFM/XF and FBS. Resting BMMSC and AdMSC, expanded in FBS or SFM/XF, demonstrated potent immunosuppressive properties in both non-primed and IFN-gamma primed conditions, whereas HPL expanded MSC exhibited diminished immunosuppressive properties. Finally, IFN gamma primed BMMSC and AdMSC expanded in SFM/XF and HPL expressed attenuated levels of IDO-1 compared to FBS. Herein, we provide strong evidence supporting the use of the FDA-approved SFM/XF medium, in contrast to the HPL medium, for the expansion of MSC towards therapeutic applications. PMID- 26564251 TI - Hormonal and Reproductive Factors and Risk of Myeloproliferative Neoplasms in Postmenopausal Women. AB - BACKGROUND: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown. METHODS: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare. RR and 95% confidence intervals (CI) were estimated utilizing Cox proportional hazard regression. RESULTS: After >250,000 person-years of follow-up, 257 cases of MPN were identified (172 ET, 64 PV). Ever use of hormone therapy (HT) was associated with an increased risk of ET (RR = 1.63; 95% CI, 1.19-2.23) but a decreased risk of PV (RR = 0.58; 95% CI, 0.34-0.98). There were no statistically significant associations of oral contraceptives or reproductive factors with MPN risk overall, or by MPN subtype. Bilateral oophorectomy was associated with increased risk of ET (RR = 1.58; 95% CI, 1.11-2.25) and decreased risk of PV (RR = 0.32; 95% CI, 0.12-0.88). There was no association of ovulatory years with ET risk; however, there was increased risk of PV (RR = 1.68 for >36.8 compared with <=27.6 years; P trend = 0.045). Adjustment for potential confounding factors did not alter these associations. CONCLUSIONS: HT use and bilateral oophorectomy had opposite associations for ET and PV. Except for ovulatory years and PV risk, reproductive history did not appear to play a role in the etiology of MPN. IMPACT: This study suggests different mechanistic impacts of estrogen, and perhaps distinct etiologies, for the two major MPN subtypes. PMID- 26564252 TI - Electrodiagnostic Evaluation of Individuals Implanted With Extracellular Matrix for the Treatment of Volumetric Muscle Injury: Case Series. AB - BACKGROUND: Electrodiagnosis can reveal the nerve and muscle changes following surgical placement of an extracellular matrix (ECM) bioscaffold for treatment of volumetric muscle loss (VML). OBJECTIVE: The purpose of this study was to characterize nerve conduction study (NCS) and electromyography (EMG) changes following ECM bioscaffold placement in individuals with VML. The ability of presurgical NCS and EMG to be used as a tool to help identify candidates who are likely to display improvements postsurgically also was explored. DESIGN: A longitudinal case series design was used. METHODS: The study was conducted at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Eight individuals with a history of chronic VML participated. The intervention was surgical placement of an ECM bioscaffold at the site of VML. The strength of the affected region was measured using a handheld dynamometer, and electrophysiologic evaluation was conducted on the affected limb with standard method of NCS and EMG. All measurements were obtained the day before surgery and repeated 6 months after surgery. RESULTS: Seven of the 8 participants had a preoperative electrodiagnosis of incomplete mononeuropathy within the site of VML. After ECM treatment, 5 of the 8 participants showed improvements in NCS amplitude or needle EMG parameters. The presence of electrical activity within the scaffold remodeling site was concomitant with clinical improvement in muscle strength. LIMITATIONS: This study had a small sample size, and participants served as their own controls. The electromyographers and physical therapists performing the evaluation were not blinded. CONCLUSIONS: Electrodiagnostic data provide objective evidence of physiological improvements in muscle function following ECM placement at sites of VML. Future studies are warranted to further investigate the potential of needle EMG as a predictor of successful outcomes following ECM treatment for VML. PMID- 26564253 TI - Examining the Association Between Comorbidity Indexes and Functional Status in Hospitalized Medicare Fee-for-Service Beneficiaries. AB - BACKGROUND: Medicare data from acute hospitals do not contain information on functional status. This lack of information limits the ability to conduct rehabilitation-related health services research. OBJECTIVE: The purpose of this study was to examine the associations between 5 comorbidity indexes derived from acute care claims data and functional status assessed at admission to an inpatient rehabilitation facility (IRF). Comorbidity indexes included tier comorbidity, Functional Comorbidity Index (FCI), Charlson Comorbidity Index, Elixhauser Comorbidity Index, and Hierarchical Condition Category (HCC). DESIGN: This was a retrospective cohort study. METHODS: Medicare beneficiaries with stroke, lower extremity joint replacement, and lower extremity fracture discharged to an IRF in 2011 were studied (N=105,441). Data from the beneficiary summary file, Medicare Provider Analysis and Review (MedPAR) file, and Inpatient Rehabilitation Facility-Patient Assessment Instrument (IRF-PAI) file were linked. Inpatient rehabilitation facility admission functional status was used as a proxy for acute hospital discharge functional status. Separate linear regression models for each impairment group were developed to assess the relationships between the comorbidity indexes and functional status. Base models included age, sex, race/ethnicity, disability, dual eligibility, and length of stay. Subsequent models included individual comorbidity indexes. Values of variance explained (R(2)) with each comorbidity index were compared. RESULTS: Base models explained 7.7% of the variance in motor function ratings for stroke, 3.8% for joint replacement, and 7.3% for fracture. The R(2) increased marginally when comorbidity indexes were added to base models for stroke, joint replacement, and fracture: Charlson Comorbidity Index (0.4%, 0.5%, 0.3%), tier comorbidity (0.2%, 0.6%, 0.5%), FCI (0.4%, 1.2%, 1.6%), Elixhauser Comorbidity Index (1.2%, 1.9%, 3.5%), and HCC (2.2%, 2.1%, 2.8%). LIMITATION: Patients from 3 impairment categories were included in the sample. CONCLUSIONS: The 5 comorbidity indexes contributed little to predicting functional status. The indexes examined were not useful as proxies for functional status in the acute settings studied. PMID- 26564254 TI - Opportunities for Regenerative Rehabilitation and Advanced Technologies in Physical Therapy: Perspective From Academia. AB - As rehabilitation specialists, physical therapists must continue to stay current with advances in technologies to provide appropriate rehabilitation protocols, improve patient outcomes, and be the preferred clinician of choice. To accomplish this vision, the physical therapy profession must begin to develop a culture of lifelong learning at the early stages of education and clinical training in order to embrace cutting-edge advancements such as stem cell therapies, tissue engineering, and robotics, to name a few. The purposes of this article are: (1) to provide a current perspective on faculty and graduate student awareness of regenerative rehabilitation concepts and (2) to advocate for increased integration of these emerging technologies within the doctor of physical therapy (DPT) curriculum. An online survey was designed to gauge awareness of principles in regenerative rehabilitation and to determine whether the topic was included and assessed in doctoral curricula. The survey yielded 1,006 responses from 82 DPT programs nationwide and indicated a disconnect in familiarity with the term "regenerative rehabilitation" and awareness of the inclusion of this material in the curriculum. To resolve this disconnect, the framework of the curriculum can be used to integrate new material via guest lecturers, interdisciplinary partnerships, and research opportunities. Successfully mentoring a generation of clinicians and rehabilitation scientists who incorporate new medical knowledge and technology into their own clinical and research practice depends greatly on sharing the responsibility among graduate students, professors, the American Physical Therapy Association (APTA), and DPT programs. Creating an interdisciplinary culture and integrating regenerative medicine and rehabilitation concepts into the curriculum will cultivate individuals who will be advocates for interprofessional behaviors and will ensure that the profession meets the goals stated in APTA Vision 2020. PMID- 26564255 TI - Individual Differences in Premotor Brain Systems Underlie Behavioral Apathy. AB - Lack of physical engagement, productivity, and initiative-so-called "behavioral apathy"--is a common problem with significant impact, both personal and economic. Here, we investigate whether there might be a biological basis to such lack of motivation using a new effort and reward-based decision-making paradigm, combined with functional and diffusion-weighted imaging. We hypothesized that behavioral apathy in otherwise healthy people might be associated with differences in brain systems underlying either motivation to act (specifically in effort and reward based decision-making) or in action processing (transformation of an intention into action). The results demonstrate that behavioral apathy is associated with increased effort sensitivity as well as greater recruitment of neural systems involved in action anticipation: supplementary motor area (SMA) and cingulate motor zones. In addition, decreased structural and functional connectivity between anterior cingulate cortex (ACC) and SMA were associated with increased behavioral apathy. These findings reveal that effort sensitivity and translation of intentions into actions might make a critical contribution to behavioral apathy. We propose a mechanism whereby inefficient communication between ACC and SMA might lead to increased physiological cost--and greater effort sensitivity- for action initiation in more apathetic people. PMID- 26564257 TI - Recovery of manganese and zinc from spent Zn-C cell powder: Experimental design of leaching by sulfuric acid solution containing glucose. AB - The spent Zn-C cell powder, containing ZnMn2O4, ZnO, MnO(OH) and possibly Mn2O3 and Mn3O4, can be leached by a sulfuric acid solution mixed with some glucose. The leaching is found to be dependent on solid to liquid (S/L) ratio, amount of glucose, concentration of sulfuric acid solution, time and pulp agitation speed. For 5g powder (S), 1h leaching time and 300rpm pulp agitation speed, two-level four-factor (2(4)) experimental designs have been carried out to derive models for extraction of both Mn(II) and Zn(II). Amount of glucose (G, g), concentration of H2SO4 solution (C, mol/L), volume of H2SO4 solution as leachant (L, mL) and leaching temperature (T, degrees C) are considered as factors (variables). The model in both cases consists of mean, factor effects and interaction effects. The four-factor interaction effect is observed in neither of the cases. Some two factor and three-factor effects are found to have produced positive or negative contributions to dissolution percentage in both cases. The models are examined for comparison with experimental results with good fits and also used for optimization of factors. At optimized condition (G=0.50g, C=2mol/L, L=250mL and T=100 degrees C), an aliquot of 5g powder in 1h and at 300rpm produces a solution containing (7.08+/-0.10)g/L Mn(II) and (2.20+/-0.06)g/L Zn(II) corresponding to almost 100% extraction of both metal ions. PMID- 26564258 TI - Cobalt products from real waste fractions of end of life lithium ion batteries. AB - An innovative process was optimized to recover Co from portable Lithium Ion Batteries (LIB). Pilot scale physical pretreatment was performed to recover electrodic powder from LIB. Co was extracted from electrodic powder by a hydrometallurgical process including the following main stages: leaching (by acid reducing conditions), primary purification (by precipitation of metal impurities), solvent extraction with D2EPHA (for removal of metal impurities), solvent extraction with Cyanex 272 (for separation of cobalt from nickel), cobalt recovery (by precipitation of cobalt carbonate). Tests were separately performed to identify the optimal operating conditions for precipitation (pH 3.8 or 4.8), solvent extraction with D2EHPA (pH 3.8; Mn/D2EHPA=4; 10% TBP; two sequential extractive steps) and solvent extraction with Cyanex 272 (pH 3.8; Cyanex/Cobalt=4, 10% TBP, one extractive step). The sequence of optimized process stages was finally performed to obtain cobalt carbonate. Products with different degree of purity were obtained depending on the performed purification steps (precipitation with or without solvent extraction). 95% purity was achieved by implementation of the process including the solvent extraction stages with D2EHPA and Cyanex 272 and final washing for sodium removal. PMID- 26564259 TI - Editorial. PMID- 26564256 TI - Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex. AB - Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory "barrel" cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID- 26564261 TI - ASCO 2015 update on melanoma. PMID- 26564260 TI - Assesment of apoptosis induced changes in scattering using optical coherence tomography. AB - The aim of this study is to identify changes in scattering with optical coherence tomography (OCT) and relate these measurements with mitochondrial changes during the initiation of apoptosis. Human retinal pigment epithelial cells were cultured and apoptosis was induced using 10% alcohol. Using the attenuation coefficient and backscattering, changes were measured during cell death in a cell-pellet and monolayer respectively. To confirm apoptosis, fluorescent activated cell sorting was used. Mitochondrial activity during apoptosis was assessed using an oxidative stress assay and fluorescent confocal microscopy. Pelleted apoptotic cells measured with OCT showed a clear rise while untreated cells showed a very small increase in attenuation coefficient. Monolayered apoptotic cells displayed a distinct increase, while untreated cells showed a small increase in the backscattering. Apoptosis was confirmed by FACS experiments. Mitochondrial changes during the onset of apoptosis were also measured. The results demonstrate that apoptotic cell death could be monitored in real-time by OCT. Changes in the scattering after induction of apoptosis are likely to be related to changes in the intracellular morphology. Oxidative stress-induced mitochondrial swelling could be responsible for the initial increase, while cell blebbing and secondary necrosis subsequently for the observed decrease in scattering. PMID- 26564262 TI - Emotion in obesity discourse: understanding public attitudes towards regulations for obesity prevention. AB - Intense concern about obesity in the public imagination and in political, academic and media discourses has catalysed advocacy efforts to implement regulatory measures to reduce the occurrence of obesity in Australia and elsewhere. This article explores public attitudes towards the possible implementation of regulations to address obesity by analysing emotions within popular discourses. Drawing on reader comments attached to obesity-relevant news articles published on Australian news and current affairs websites, we examine how popular anxieties about the 'obesity crisis' and vitriol directed at obese individuals circulate alongside understandings of the appropriate role of government to legitimise regulatory reform to address obesity. Employing Ahmed's theorisation of 'affective economies' and broader literature on emotional cultures, we argue that obesity regulations achieve popular support within affective economies oriented to neoliberal and individualist constructions of obesity. These economies preclude constructions of obesity as a structural problem in popular discourse; instead positioning anti-obesity regulations as a government-endorsed vehicle for discrimination directed at obese people. Findings implicate a new set of ethical challenges for those championing regulatory reform for obesity prevention. PMID- 26564263 TI - Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells. AB - Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway. PMID- 26564264 TI - Charge-switching amino acids-based cationic lipids for efficient gene delivery. AB - A series of charge-switching amino acids-based cationic lipids 4a-4e bearing a benzyl ester at the terminus of the acyl chain, but differing in the polar-head group were prepared. The physicochemical properties of these lipids, including size, zeta potential and cellular uptake of the lipoplexes formed from with DNA, as well as the transfection efficiency (TE), were investigated. The results showed that the chemical structure of the cationic head-group clearly affects the physicochemical parameters of the amino acid-based lipids and especially the TE. The selected lipid, 4c gave 2.1 times higher TE than bPEI 25k in the presence of 10% serum in HeLa cells, with little toxicity. PMID- 26564265 TI - Click-based synthesis of bromotyrosine alkaloid analogs as potential anti-biofilm leads for SAR studies. AB - A library of triazole-based analogs of bromotyramine alkaloids such as verongamines, hemibastadins, pseudoceramine D and clavatidine E was designed in order to identify promising leads that may help in the control of bacterial biofilms. Twenty-three compounds were screened for their biofilm inhibitory activity against three strains of Gram-negative bacteria. SAR studies revealed that hemibastadins analogs were the most active compounds which act as inhibitors of biofilm development (EC50 8.8-29MUM) without effect on bacterial growth even at high concentrations (100MUM). PMID- 26564266 TI - Identification, synthesis and pharmacological evaluation of novel anti-EV71 agents via cyclophilin A inhibition. AB - In this work, the relationship between cyclophilin A (CypA) and EV71 prompted us to screen a series of small molecular CypA inhibitors which were previously reported by our group. Among them, compounds 1 and 2 were discovered as non immunosuppressive anti-EV71 agents with an EC50 values of 1.07+/-0.17MUM and 3.36+/-0.45MUM in virus assay, respectively, which were desirably for the further study. The subsequent chemical modifications derived a novel class of molecules, among which compound 11 demonstrated the most potent anti-EV71 activity in virus assay (EC50=0.37+/-0.17MUM), and low cytotoxicity (CC50>25MUM). The following CypA enzyme inhibition studies indicated that there was not only the enzyme inhibition activity, undoubtedly important, functioning in the antiviral process, but also some unknown mechanisms worked in combination, and the further study is underway in our laboratory. Nevertheless, to the best of our knowledge, compound 11 was probably the most potent small molecular anti-EV71 agent via CypA inhibitory mechanism to date. Consequently, our study provided a new potential small molecule for curing EV71 infection. PMID- 26564267 TI - Towards Carbon-Neutral CO2 Conversion to Hydrocarbons. AB - With fossil fuels still predicted to contribute close to 80 % of the primary energy consumption by 2040, methods to limit further CO2 emissions in the atmosphere are urgently needed to avoid the catastrophic scenarios associated with global warming. In parallel with improvements in energy efficiency and CO2 storage, the conversion of CO2 has emerged as a complementary route with significant potential. In this work we present the direct thermo-catalytic conversion of CO2 to hydrocarbons using a novel iron nanoparticle-carbon nanotube (Fe@CNT) catalyst. We adopted a holistic and systematic approach to CO2 conversion by integrating process optimization-identifying reaction conditions to maximize conversion and selectivity towards long chain hydrocarbons and/or short olefins-with catalyst optimization through the addition of promoters. The result is the production of valuable hydrocarbons in a manner that can approach carbon neutrality under realistic industrial process conditions. PMID- 26564268 TI - Whatever happened to the Norwegian Medical Need Clause? Lessons for current debates in EU pharmaceutical regulation. AB - Until 1994, pharmaceutical products seeking market authorisation in Norway were required to demonstrate a fulfilment of unmet medical need. This clause enabled the national regulator to dramatically limit the number of products on the market whilst encouraging price competition to keep drug expenditure low and was credited with encouraging the development of drugs with genuine added therapeutic value and reducing the incidence of antimicrobial resistance. Norway was forced to abandon its Medical Need Clause (MNC) when it joined the European Economic Area as it was incompatible with the acquis communautaire of the European Union. This article reviews Norway's experience with its MNC in light of contemporary debates in European health policy. It discusses the potential contribution of an MNC-style regulation to improving health, reducing illness, ensuring sustainable health systems and fostering pharmaceutical innovation. It concludes by asking how these findings can inform current European Union debates over the growing cost of prescription drugs and direction of pharmaceutical development. PMID- 26564269 TI - Insights into body composition adaptation: should we reconsider the use of Body Mass Index in some sports? AB - BACKGROUND: The purposes of this study were to indentify the under/overweight/obese frequencies by Body Mass Index (BMI) and body fat percentage (BF%) in athletes within groups of sport and to investigate the accuracy of the BMI as a measure of BF%. METHODS: Cross-sectional design study on elite male athletes (N.=2234, aged 22+/-4 years) from 51 sports disciplines who were classified according to two different sport classifications: predominant characteristic of training (four group model) and type and intensity of exercise (nine group model). All athletes underwent full anthropometric testing. RESULTS: After stratification, the majority of athletes were in normal weight category. According to 4 group model, BMI is showed as statistically significant, reliable and independent predictor of BF% in all groups of sports. In nine groups model all correlated parameters were positive for athletes being statistically significant (P<0.001) with exception of group LSMD, MSMD and HSMD (P>0.05). The highest positive correlation between BMI and BF% was in group MSLD (r=0.53; P<0.001) and in power sports group (r=0.24; P<0.001). CONCLUSIONS: BMI could be an accurate predictor of BF% in athletes but that depends on group of sport. Our results suggest the BMI could use only in power and MSLD groups of sport. PMID- 26564270 TI - The effect of the oxygen uptake-power output relationship on the prediction of supramaximal oxygen demands. AB - BACKGROUND: The aim of this study was to investigate the relationship between oxygen uptake (VO2) and power output at intensities below and above the lactate threshold (LT) in cyclists; and to determine the reliability of supramaximal power outputs linearly projected from these relationships. METHODS: Nine male cyclists (mean+/-standard deviation age: 41+/-8 years; mass: 77+/-6 kg, height: 1.79+/-0.05 m and VO2max: 54+/-7 mL?kg-1?min-1) completed two cycling trials each consisting of a step test (10*3 min stages at submaximal incremental intensities) followed by a maximal test to exhaustion. The lines of best fit for VO2 and power output were determined for: the entire step test; stages below and above the LT, and from rolling clusters of five consecutive stages. Lines were projected to determine a power output predicted to elicit 110% peak VO2. RESULTS: There were strong linear correlations (r>=0.953; P<0.01) between VO2 and power output using the three approaches; with the slope, intercept, and projected values of these lines unaffected (P>=0.05) by intensity. The coefficient of variation of the predicted power output at 110% VO2max was 6.7% when using all ten submaximal stages. CONCLUSIONS: Cyclists exhibit a linear VO2 and power output relationship when determined using 3 min stages, which allows for prediction of a supramaximal intensity with acceptable reliability. PMID- 26564271 TI - Effects of a physical activity program on the urinary collagen crosslinks in pre- and postmenopausal women. AB - BACKGROUND: This study analyzes the effects of physical exercise on urinary collagen crosslinks, pyridinoline (PYD) and deoxipyridinoline (DPD), in women. METHODS: Thirty premenopausal (PRE) and 40 postmenopausal (PST) women took part in a six month randomized controlled trial of moderate physical exercise. Moreover, skinfold thickness, muscle strength and flexibility were evaluated. RESULTS: Basal values of urinary PYD and DPD were higher in postmenopausal women versus premenopausal women (P<0.01). Physical exercise increased in both groups urinary PYD levels (P<0.05) and urinary DPD levels in postmenopausal women (P<0.05). After the exercise program, no changes were observed in the levels of urinary DPD in premenopausal women. Significant improvements in flexibility, muscle strength and decrease in skinfolds thickness were observed in the exercise group. No changes were observed in non-exercise group. CONCLUSIONS: In conclusion, the physical activity program produced beneficial effects on muscle strength and flexibility and changes in the musculoskeletal system. Also, the physical activity program led to a non-pathological increase in the urinary elimination of bone reabsorption and collagen metabolism biomarkers. PMID- 26564272 TI - The effect of a gluteal activation protocol on sprint and drop jump performance. AB - BACKGROUND: This study examined the acute effect of gluteal activation exercises on 10 m sprints and drop jumps (DJ)s performed on a force sledge apparatus. METHODS: Twelve participants completed pre-tests of 10 sprints and 10 DJs with one minute recovery between sprints or jumps. For the 10 m sprints, contact, flight, 5 m and 10 m times were recorded using an Optojump Next system. For DJs, height jumped, contact and flight times, Reactive Strength Index and peak forces were recorded via a force-sledge system. In the post-tests, the participants completed a gluteal activation exercise protocol immediately before the sprint or DJ tests. Results were analyzed using an adapted typical error method and repeated measures ANOVA. RESULTS: The repeated measures ANOVA found significant performance related improvements in 5 m and 10 m sprint times, flight and contact times for each step and significant improvements in all jump measures (P<0.05). By contrast, the typical error method showed relatively few instances of potentiation and no clear patterns of fatigue followed by potentiation across all participants in sprint and DJ performances following the gluteal activation protocol. CONCLUSIONS: The results suggest that gluteal activation exercises do not produce a consistent acute performance enhancing affect; however, their role in injury prevention is unclear. PMID- 26564273 TI - When celebrations go wrong: a case series of injuries after celebrating in sports. AB - BACKGROUND: Athletes often engage in various celebration maneuvers during sports events. These celebrations can result in acute injuries. Our objective was to document publicized injuries in collegiate and professional athletes resulting from celebrations and examine associated variables. METHODS: A retrospective case series study was performed based on internet searches performed using the following major sporting news websites: espn.com, SI.com, bleacherreport.com, totalprosports.com, cbssports.com, larrybrownspots.com, nfl.com, and mlb.com and PubMed. Keywords used during these searches included "celebration injury", "score celebration", and "surgery after celebration". These same sources were used to document the sport, athlete's age at time of injury, celebration action, type of injury, previous play, and whether surgery was required. RESULTS: A total of 62 athletes sustained 62 injuries resulting from various types of celebrations. All but two athletes were males, and the average age was 26.5 years old. The injuries occurred between 1993 and 2015. Sixteen (25.8%) of these injuries required surgery. Professional soccer players accounted for the greatest number of these injuries with a total of 22 injuries. One celebration in a professional soccer player resulted in a cervical spinal cord injury and subsequent death. Common celebration maneuvers included leaping into the air, pile ups, sliding, and somersaults. CONCLUSIONS: Serious injuries occur in a diversity of sports after celebrations. The most prevalent celebration maneuvers resulting in injuries included sliding and pile ups. The most common injuries were ACL ruptures and ankle sprains. The most serious injuries were a spinal cord injury and ankle fractures. Sixteen (25.8%) of the injuries required surgery. By encouraging athletes to temper excessive celebrations and prohibiting certain types of celebrations, many injuries may be prevented. PMID- 26564275 TI - [Nothing to disclose?]. PMID- 26564274 TI - Impact of physical activity during pregnancy on obstetric outcomes in obese women. AB - BACKGROUND: Maternal obesity is associated with complications and adverse outcomes during the labor and delivery process. In pregnant women with a healthy body weight, maternal physical activity during pregnancy is associated with better obstetric outcomes; however, the effect of maternal physical activity during pregnancy on obstetric outcomes in obese women is not known. The purpose of the study was to determine the influence of self-reported physical activity levels on obstetric outcomes in pregnant obese women. METHODS: A retrospective chart review was performed on 48 active obese women and 48 inactive obese women (N.=96) who received prenatal care and delivered at the medical center during the past five years. Obstetric and neonatal outcomes were compared between the active and inactive groups. RESULTS: Obese women who were active during pregnancy spent less total time in labor (13.4 hours vs. 19.2 hours, P=0.048) and were less likely to request an epidural (92% vs. 100%, P=0.04). When stratified by parity, active multiparous women spent significantly less total time in labor compared to inactive multiparous (6.2 hours vs. 16.7 hours, P=0.018). There were no statistical differences between groups in rates of cesarean deliveries or neonatal outcomes. CONCLUSIONS: Maternal physical activity during pregnancy appears to improve obstetric outcomes in obese women, and this improvement may be more pronounced among multiparous women. Our finding is of particular importance as pregnant obese women are at higher risk for adverse labor and delivery outcomes. PMID- 26564276 TI - Inactivation of Clostridium difficile in sewage sludge by anaerobic thermophilic digestion. AB - There has been an increase in community-associated Clostridium difficile infections with biosolids derived from wastewater treatment being identified as one potential source. The current study evaluated the efficacy of thermophilic digestion in decreasing levels of C. difficile ribotype 078 associated with sewage sludge. Five isolates of C. difficile 078 were introduced (final density of 5 log CFU/g) into digested sludge and subjected to anaerobic digestion at mesophilic (36 or 42 degrees C) or thermophilic (55 degrees C) temperatures for up to 60 days. It was found that mesophilic digestion at 36 degrees C did not result in a significant reduction in C. difficile spore levels. In contrast, thermophilic sludge digestion reduced endospore levels at a rate of 0.19-2.68 log CFU/day, depending on the strain tested. The mechanism of lethality was indirect by stimulating germination then inactivating the resultant vegetative cells. Acidification of sludge by adding acetic acid (6 g/L) inhibited the germination of spores regardless of the sludge digestion temperature. In conclusion, thermophilic digestion can be applied to reduce C. difficile in biosolids, thereby reducing the environmental burden of the enteric pathogen. PMID- 26564277 TI - Three-dimensional reconstruction of human placental vascular network using in vitro MRI data. PMID- 26564278 TI - The Meryon Lecture at the 18th Annual Meeting of the Meryon Society Wolfson College, Oxford, UK, 12th September 2014: Neuromuscular disorders in Roma (Gypsies)--collaborative studies, epidemiology, community-based carrier testing program and social activities. PMID- 26564279 TI - Urea-induced binding between diclofenac sodium and bovine serum albumin: a spectroscopic insight. AB - We investigated the interaction of diclofenac sodium (Dic.Na) with bovine serum albumin (BSA) in the absence and presence of urea using different spectroscopic techniques. A fluorescence quenching study revealed that the Stern-Volmer quenching constant decreases in the presence of urea, decreasing further at higher urea concentrations. The binding constant and number of binding sites were also evaluated for the BSA-Dic.Na interaction system in the absence and presence of urea using a modified Stern-Volmer equation. The binding constant is greater at high urea concentrations, as shown by the fluorescence results. In addition, for the BSA-Dic.Na interaction system, a static quenching mechanism was observed, which was further confirmed using time-resolved fluorescence spectroscopy. UV-vis spectroscopy provided information about the formation of a complex between BSA and Dic.Na. Circular dichroism was carried out to explain the conformational changes in BSA induced by Dic.Na in the absence and presence of urea. The presence of urea reduced the alpha-helical content of BSA as the Dic.Na concentration varied. The distance r between the donor (BSA) and acceptor (Dic.Na) was also obtained in the absence and presence of urea, using fluorescence resonance energy transfer. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26564280 TI - Metabolic Syndrome: The drums are beating. PMID- 26564281 TI - Comparison of letrazole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. AB - OBJECTIVE: To compare the efficacy of letrazole in the induction of ovulation with clomiphene citrate in patients with polycystic ovary syndrome and primary infertility. METHODS: The prospective clinical trial was conducted at Basrah Maternity and Child Hospital, Basrah, Iraq, between January 2012 and April 2013, and comprised women with polycystic ovarian syndrome and primary infertility who were randomised into 2 groups. Group A received100-200mg clomiphene citrate daily while group 2 received letrazole (2.5-5mg) daily. Both groups were followed by ultrasound until the dominant follicle reached a diameter >18mm, human chorionic gonadotropin10.000 U/L was given and timed intercourse was advised. RESULTS: Of the 75 subjects in the study, 40(53.3%) were in group A and 35(46.6%) in group B. The mean age in group A was 25.3+2.1 years versus 26.1+1.3 years in group B (p=0.05). The number of mature follicles was significantly lower, but the endometrial thickness and ovulation were significantly higher in group B than in group A (p<0.05 each). There was no significant difference in pregnancy rate between the two groups (p>0.05). CONCLUSIONS: Letrazole may have a role as the first-line treatment for unovulatory patients with polycystic ovary syndrome. PMID- 26564282 TI - The association between 25-dehydroxy vitamin D and lower respiratory infection in children aged less than "5" years in Imam Reza hospital, Bojnurd, Iran. AB - OBJECTIVE: To clarify the association between vitamin D deficiency and acute respiratory infection in children below age 5 years. METHODS: The cross-sectional study was conducted at Imam Reza Hospital in Bojnurd, Iran, in June 2013 and comprised 90 children below 5 years of age suffering from respiratory infections. They was selected on the basis of purposive sampling and were then categorised into two equal groups of 'acute' and 'non-acute' respiratory infection. Data collection was done using a questionnaire and serum level of 25 dehydroxycalcciferol was measured. SPSS 11 was used to analyse and interpret the data. RESULTS: In the group of children with respiratory disorders, 9 (42.9%) exhibited vitamin D deficiency. There were no significant differences between the two groups in terms of demographic characteristics such as age, intrauterine age, weight, birth-weight, head circumference, height, gender, living area and respiratory distress (p>0.05 each). Vitamin D deficiency showed no meaningful statistical relation with acute respiratory infections (p>0.05). CONCLUSIONS: More studies with higher sample size and are recommended. PMID- 26564283 TI - Bedside heart type fatty acid binding protein (H-FABP): Is an early predictive marker of cardiac syncope. AB - OBJECTIVE: To determine the value of bedside heart-type fatty acid binding protein in diagnosis of cardiac syncope in patients presenting with syncope or presyncope. METHODS: The prospective study was conducted at Ankara Numune Training and Research Hospital, Ankara, Turkey, between September 1, 2010, and January 1, 2011, and comprised patients aged over 18 years who presented with syncope or presyncope. Patients presenting to emergency department within 4 hours of syncope or presyncope underwent a bedside heart-type fatty acid binding protein test measurement. SPSS 16 was used for statistical analysis. RESULTS: Of the 100 patients evaluated, 22(22%) were diagnosed with cardiac syncope. Of them, 13(59.1%) patients had a positive and 9(40.9%) had a negative heart-type fatty acid binding protein result. Consequently, the test result was 12.64 times more positive in patients with cardiac syncope compared to those without. CONCLUSIONS: Bedside heart-type fatty acid binding protein, particularly at early phase of myocardial injury, reduces diagnostic and therapeutic uncertainity of cardiac origin in syncope patients. PMID- 26564285 TI - Role of acute pain service in optimizing postoperative pain relief in a tertiary care teaching hospital. AB - OBJECTIVE: To assess the frequency and types of adjustments that acute pain service makes to postoperative analgesic regimes to improve pain relief or treat side effects. METHODS: The prospective observational study was conducted at the Aga Khan University Hospital, Karachi, from December 1, 2012, to March 31, 2013. Data was collected from Acute Pain Service register four hours after the pain rounds by a Service member not involved in rounds. Data was collected on a standardised form and analysed using SPSS 19. RESULTS: Of the 323 patients, 209(65%) were receiving epidural infusions and 114(35%) were receiving intravenous patient-controlled analgesia. Overall, 114(35%) required action by Acute Pain Service; 76(66.6%) with epidural infusions and 38(33.3%) intravenous analgesia. Besides, 98(85.9%) had inadequate pain relief, 61(62%) with epidural and 37(38%) with analgesia. Post-intervention, motor block occurred in 13(11.4%) patients, who were managed by change of patient?'s position and/or lowering the concentration of epidural solution. Improvement was seen in all patients after the adjustments. CONCLUSIONS: Acute Pain Service played an important role in improving the quality of postoperative pain relief and management of analgesia related side effects. Regular feedback to the primary anaesthesiologist can lead to improved practices. PMID- 26564284 TI - Consanguinity ratio in b-thalassemia major patients in District Bannu. AB - OBJECTIVE: To assess the frequency of consanguinity in b-thalassemia major patients and its association with age, gender and hepatitis C virus antibody positivity. METHODS: The cross-sectional study was conducted from June 2013 to July 2014 at various hospitals of district Bannu in the North Western Khyber Pakhtunkhwa province of Pakistan. Data was recorded on a predesigned questionnaire. RESULTS: Out of 180 subjects, 133(74%) parents were cousins, while 47(26%) were unrelated. The frequency of anti-hepatitis C virus antibody positivity was 14(7.77%). CONCLUSIONS: High prevalence of the disease in the study region was due to consanguineous marriages. PMID- 26564286 TI - The association of factor V leiden mutation with recurrent pregnancy loss. AB - OBJECTIVE: To determine the association of factor V Leiden mutation with recurrent pregnancy loss. METHODS: The case-control study was conducted at the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to June 2012, and comprised women of 18 to 45 years of age who had a history of recurrent pregnancy loss, and controls with no history of pregnancy loss. All the subjects belonged to Punjabi ethnic group. Three ml blood was taken from cases and controls and deoxyribonucleic acid was extracted. In order to identify Factor V Leiden mutation, polymerase chain reaction method was utilised combined with the amplification refractory mutation system. Data was analysed using SPSS 17. RESULTS: Of the 112 subjects, 56(50%) were in each of the two groups. The presence of factor V Leiden mutation among the cases was 3(5.4%) while it was absent among the controls. The mutation was significantly associated with recurrent pregnancy loss (p=0.017).Recurrent pregnancy loss was higher in cases than controls (p=0.001). CONCLUSIONS: Factor V Leiden mutation, Recurrent pregnancy loss, PCR (Polymerase chain reaction). PMID- 26564287 TI - Frequency and factors leading to recurrent pre-eclampsia. AB - OBJECTIVE: To determine the frequency and factors leading to recurrent preeclampsia. METHODS: The cross-sectional study was conducted at the Jinnah Post Graduate Medical Centre, Karachi, from January 2011 to February 2012, and comprised parous subjects <40 years of age with history of preeclampsia in previous pregnancy/pregnancies with singleton pregnancy and gestational age of >20 weeks. Gestational age was determined by early scan with preeclampsia in index pregnancy. Data was collected through a specialised questionnaire and analysed using SPSS 16. RESULTS: Of the 479 patients seen with preeclampsia, 121(25.26%) were of recurrent preeclampsia. The mean age of such patients was 29.7+/-4.9 years (range: 20-39 years). Further, 84(69.42%) patients were multipara and 40(33.05%) were grand multipara. Mean body mass index was 29.97+/ 6.2 (range: 18-54). Besides, 28(23.14%) patients had gestational diabetes; 7(5.78%) were known diabetics; 24(19.83%) had chronic hypertension; 2(1.7%) patients had chronic renal disease; and 1(0.8%) had connective tissue disorder. CONCLUSIONS: Being over-weight, having gestational diabetes and chronic hypertension were main risk factors leading to recurrent preeclampsia. PMID- 26564288 TI - Frequency of preterm delivery in proteinuric verses non proteinuric pregnancy induced hypertension. AB - OBJECTIVE: To compare the frequency of preterm labour associated with gestational proteinuric hypertension versus gestational non-proteinuric hypertension. METHODS: The prospective cohort study was conducted at the Department of Obstetrics & Gynaecology, Dow University of Health Sciences and Civil Hospital Karachi, from April 1 to September 30, 2012, and comprised primigravidas of more than or equal to 20th weeks of gestation having blood pressure >140/90 mm Hg. Those with gestational hypertension with proteinuria represented the exposed group, while the non-exposed group had primigravidas with gestational hypertension without proteinuria. SPSS 10 was used to analyse data. RESULTS: There were 112 subjects, with 56(50%) in each of the two groups. Mean maternal age in exposed group was 28.3+/-4.49 years and in the non-exposed group 26.08+/ 0.04 years. Mean gestational age in the exposed group was 36.89+/-4.04 weeks and in the non-exposed group 37.75+/-3.428 weeks. Women with gestational hypertension with proteinuria were more likely to deliver preterm infants compared to women with gestational hypertension without proteinuria (p=0.009). CONCLUSIONS: Gestational proteinuric hypertension increased the risk of preterm labour, therefore vigilant monitoring of gestational proteinuric hypertension is important. PMID- 26564289 TI - Elevated serum level of human alkaline phosphatase in obesity. AB - OBJECTIVE: To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. METHODS: The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass. INDEX: normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. RESULTS: Of the 197 subjects, 97(49%) were obese and 100(51%) were non-obese. The serum alkaline phosphatase level increased in obese (214+/-6.4 IU/L) compared to the non-obese subjects (184.5+/-5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. CONCLUSIONS: Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity. PMID- 26564290 TI - Bcl-2 and p53 expression in hepatic tissues of Egyptian patients with Chronic Hepatitis C. AB - OBJECTIVE: To investigate B-cell-lymphoma-2 and tumour protein p53 expression in hepatic tissues of human cases of Chronic Hepatitis C. METHODS: The case-control study was conducted from December 2011 to February 2014 at the out-patient department of Gastroenterology Surgical Centre, Faculty of Medicine, Mansoura University, Mansoura, Egypt, and comprised healthy individuals and treatment naive chronic hepatitis C patients who had undergone liver biopsy. Liver biopsy was taken from patients prior to antiviral therapy or any other anti-fibrotic therapy. Serum marker levels were investigated on the day of biopsy or within 5 days after it. Blood platelet count was also investigated using standard methods. Formalin-fixed, paraffin-embedded sections were stained with haematoxylin and eosin and for apoptosis detection, B-cell-lymphoma-2 and tumour protein p53 expression in tissue was investigated through immunohistochemistry. Slides were labelled with patient identification numbers and then reviewed and graded blindly by a senior pathologist. SPSS 16 was used for statistical analysis. RESULTS: Of the 140 subjects in the study, 120(85.7%) were patients with a mean age of 39+/ 8.7 years (range: 11-64 years) and 20(14.3%) were healthy controls with a mean age of 38.6+/-7.4 years (range: 14-66 years). The patients had higher body mass index but the difference was not significant (p>0.05), while the difference in the levels of alanine transaminase, aspartate aminotransferase, alpha fetoprotein and platelet count was significant (p<0.05 each). The highest expression of B cell-lymphoma-2 was detected in chronic hepatitis C stage, while the highest expression of p53 was detected in hepatocellular carcinoma stage. CONCLUSIONS: The expression of both B-cell-lymphoma-2 and tumour protein p53 might play diagnostic role during the different stages of the disease. PMID- 26564291 TI - Efficacy and safety of semirigid ureteroscopy combined with holmium: YAG laser in the treatment of upper urinary tract calculi: Is it a good alternative treatment option of flexible ureteroscopy for developing countries? AB - OBJECTIVE: To assess the success rates of endoscopic management of upper ureteral stones using semirigid ureterorenoscopy and holmium: YAG laser lithotripters. METHODS: A total of 74 patients with an established diagnosis of upper ureteric stone and scheduled for endoscopic ureteral stone treatment were retrospectively evaluated. Failure was defined as the inability to contact or fragment the stone, migration of the stone into the renal pelvis and difficulty in visualizing the stone for the second time. Success rates and influencing factors as for stone free state were investigated. RESULTS: Mean age of our patients was 45.99+/-15.00 (range: 24-82) years. In 14 of 74 patients procedural failure was observed. Double J stents were implanted in 65 % of the patients and ureteral catheterization was performed on 20% of them. The total success rate was 81.1 %. Major complication rate was 1.1 percent. Factors effecting the success rate as gender, age, body mass index, grade of hydronephrosis and stone size were evaluated and only age was found to be statistically significant. CONCLUSIONS: Despite some potential risks, semirigid ureterorenoscopic stone extraction and holmium: YAG laser lithotripters are still safe and effective treatment alternatives for management of upper ureteral stones. PMID- 26564292 TI - Is chlorhexidine-gluconate superior than Povidone-Iodine in preventing surgical site infections? A multicenter study. AB - OBJECTIVE: To compare the efficacy of povidone-iodine and chlorhexidine gluconate scrubs in preventing surgical site infections. METHODS: The randomised controlled clinical trial was conducted from May 2012 to April 2013 in two public-sector hospitals of Pakistan; one each in Karachi and Islamabad. Patients undergoing clean or clean contaminated surgeries were included and were randomly assigned to one of the two groups: group I comprised patients whose skin was preoperatively disinfected using 10% povidone-iodine, and in group II by 2% chlorhexidine gluconate in 70% alcohol. A predesigned proforma was filled for all patients to record demographic data, diagnosis, surgical procedure and antibiotic used. Patients in both groups were followed up for one month postoperatively to monitor any signs of surgical site infections. SPSS 16 was used for statistical analysis. RESULTS: Of the 388 patients from the two hospitals, 220(57%) were in group I and 168(43%) were in group II. Surgical site infection was observed in 22(10%) cases in group I and 12(7.1%) in group II (p=0.324). Pseudomonas aeruginosa (23.5%) was the predominant pathogen associated with surgical site infections followed by Staphylococcus aureus (17.6%). CONCLUSIONS: Chlorhexidine gluconate was associated with lower infection rates compared to povidone-iodine; but it was not statistically significant. PMID- 26564293 TI - Prevalence of rheumatoid arthritis in population with arthralgia presenting to a tertiary care hospital. AB - OBJECTIVE: To evaluate patients presenting to healthcare facilities because of joint pain and subsequently diagnosed with rheumatoid arthritis. METHODS: The prospective study was conducted from August 1, 2013,to January 20, 2014, at Jinnah Postgraduate Medical Centre, Karachi, and comprised patients presenting with joint pain. A questionnaire was used to collect data, and patients were diagnosed using American College of Rheumatology / European League Against Rheumatism Rheumatoid Arthritis Classification Criteria. Data was analyzed using SPSS 20. RESULTS: Of the 320 patients approached, 316(98.7%) filled the questionnaire. Eighty five (26.9%) were diagnosed as rheumatoid arthritis. Sixty (70.5%) were females and 25 (26.3%) were males. The frequency of rheumatoid arthritis was higher in people in 4th, 5th and 6th decades of life. Twenty five (7.9%) patients had positive family history, 77 (90.2%) were chronic sufferers and only 53 (16%) agreed to follow recommended immunosuppressive therapies. 212 (67.1%) patients belonged to highly literate class. CONCLUSIONS: Proper guidance regarding the disease was found to be lacking in the urban centre. PMID- 26564294 TI - Clinical spectrum, management and outcome of neonatal candidiasis. AB - OBJECTIVE: To identify clinical spectrum, management and outcome of neonatal candidiasis. METHODS: The retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological records of all the babies admitted to the Neonatal Intensive Care Unit from January 2009 to January 2014 that were reviewed to identify those with positive candida cultures. Medical records were analysed for demographic and clinical spectrum features, management and outcome. SPSS 16 was used statistical analysis. RESULTS: Of the total 1550 neonatal admissions, 560 (36%) had positive cultures, and, of them, candida was isolated in 49(8.8%) neonates. Among them, 13(26%) had candida albicans and the rest had candida species. Majority were males 34(70%), and preterm with 30(61%) being <37 weeks. The mean birth weight was 2000+/-873 grams. Mean age at admission was 6+/-7.6 days. Overall, 39(80%) had >=2 risk factors. The commonest site of isolation was blood in 41(84%). Besides, 32 (65%) received fluconazole alone for treatment. Mean duration of anti-fungal therapy was 10+/-5 days (range: 1-21 days). Twelve (24%) neonates expired and the cause of death was candida sepsis in 10(20%) cases. Mortality was not significantly associated with gender, place of birth, gestation, risk factors, length of stay, prior antibiotic exposure or receipt of antifungal prophylaxis except those who were <=1500 grams (p<0.05). CONCLUSIONS: Approximately one in ten at-risk neonates may develop candida sepsis with high mortality. Early institution of anti-fungal therapy may prove to be life-saving. PMID- 26564295 TI - Respiratory tract infections in diabetic and non-diabetic individuals are linked with serum surfactant protein-D. AB - OBJECTIVE: To find out the rate of respiratory tract infections in diabetic and non-diabetic individuals and their relation with surfactant protein D. METHODS: The cross-sectional study was conducted at Dow University of Health Sciences, Karachi, from September 2011 to April 2012, and comprised subjects of both genders between ages of 30 and 60 years. The subjects were divided into four groups: diabetic obese, non-diabetic obese, diabetic non-obese, and non-diabetic non-obese. A structured questionnaire was used to collect information about respiratory tract infections. Serum surfactant protein D levels were analysed using human surfactant protein D enzyme-linked immunosorbent assay kit. Statistical analysis was performed using SPSS 16. RESULTS: Of the 90 subjects, there were 20(22.2%) diabetic obese, 30(33.3%) non-diabetic obese, 10(11.1%) diabetic non-obese, and 30(33.3%) non-diabetic-non-obese. The overall mean age was 36.6+/-103 years. Among the diabetic obese, 15(75%) had respiratory tract infections which was higher than the other study groups, and patients having respiratory tract infections had lower surfactant protein D levels than those who did not have infections (p=0.01). CONCLUSIONS: Diabetic obese subjects had greater rate of recurrent respiratory tract infections and had lower concentration of serum surfactant protein D compared to subjects without respiratory tract infections. PMID- 26564296 TI - Apprehensions and problems after laryngectomy: Patients' perspective. AB - OBJECTIVE: To evaluate the apprehensions, social, sexual and financial problems in patients with advanced laryngeal cancer after total laryngectomy and the impact of attending laryngeal club on these problems. METHODS: The analytical study was conducted at the Dow Medical College and Civil Hospital Karachi from January 1996 to December 2011. Patients with total laryngectomy, operated for advanced laryngeal cancer at various centres of Sindh and Balochistan, attending Laryngeal Club of Pakistan, situated at Civil Hospital Karachi, were included. All the patients were evaluated through a questionnaire covering their apprehensions regarding social, sexual and financial impact on their lives after total laryngectomy. Data was analysed using SPSS 16. RESULTS: Of the 125 patients, 120(96%) were males, and 5(4%) were females; all housewives. The overall mean age was 54.8+/-0.5 years (range: 31-65 years). Further, 92(74%) participants were worried about financial uncertainty, while 84(67%) had regrets over loss of their voice; patients worried about losing family support and facing social rejection were 23(18%) and 15(12%) respectively. Only 7(5%) patients feared losing sexual relationship with their spouse. All these apprehensions were subdued after attending the Laryngeal Club of Pakistan. Severe financial impact was faced by 55(44%) patients due to loss of job, while 05(4%) had moderate impact due to change of job with lower income and 60(48%) patients had no financial problem. A good 102(82%) participants thought the support from their friends and family was upto their expectations; 98(78%) enjoyed satisfactory sex life although with reduced frequency of 1 to 2 intercourses per month; 21(17%) were having the frequency of 3-10 per month; and 3(2%) had more than 10 per month. Only 16(13%) patients were not involved in sexual relations with their spouses due to various reasons. CONCLUSIONS: Majority of laryngectomised patients expressed apprehensions and showed some social problems after laryngectomy, especially in the initial phase which improved either with passage of time or after attending Laryngectomy Club. The main problem was financial constraints; majority had good friends and family support and enjoyed satisfactory sexual relationship with their spouse. PMID- 26564297 TI - Intraocular pressure changes associated with tracheal extubation: Comparison of sugammadex with conventional reversal of neuromuscular blockade. AB - OBJECTIVE: To compare the effects of neostigmine/atropine combination and sugammadex on intraocular pressure during tracheal extubation period. METHODS: The single-blind prospective randomised controlled study was conducted at Ordu University Research and Training Hospital from August to October 2014, and comprised patients who were randomly assigned to 2 groups according to the agent used for reversal of neuromuscular blockade. Group N received 0.05mgkg-1 neostigmine and 0.02 mgkg-1 atropine and the patients in Group S received 2mgkg-1 sugammadex intravenously. Heart rate, mean arterial pressure and intraocular pressure were measured at baseline, before the induction (T1), after the application of reversal agent (T2), and 1 (T3), 3 (T4), 5 (T5) and 10 (T6) minutes after the extubation. SPSS 16 was used for statistical analysis. RESULTS: There were 36 patients in the study; 18(50%) in each group. There was no significant difference between the groups in terms of age, gender and body mass index (p>0.05 each). Intraocular pressure was significantly higher when the baseline level was compared with all measurement intervals in Group N (p<0.05 each). In Group S, it showed no significant difference at T2 (p>0.05) whereas it was significantly higher at all other measurement intervals (p<0.05 each). Intergroup comparisons showed statistically significant difference in heart rate and mean arterial pressure levels at T2 interval which were higher in Group N (p<0.01). Intraocular pressure levels at T2 and T3 intervals were significantly higher in Group N (p<0.01). CONCLUSIONS: Lower end-extubation intraocular pressure levels were obtained when sugammadex was used as a neuromuscular block reversal agent in comparison with neostigmine-atropine combination. Sugammadex may be a better option for the reversal of neuromuscular blockade and intraocular pressure increase should be avoided in patients with glaucoma or penetrating eye injury. PMID- 26564298 TI - Oral manifestations of asthmatic patients. AB - The effect of asthma on oral health is the subject of debate among dental practitioners. The current study was planned to investigate the oral manifestations of asthmatics compared to healthy subjects. The study group composed of 100 asthmatics and 100 age-matched healthy controls. The caries status based on Decayed/Missing/Filled Teeth (DMFT) criteria and oral lesion were evaluated in all subjects. The mean age of the asthmatics group was 47.5+/-3.5 years and in the control group it was 43.5+/-3.0 years. Asthmatics included 45(45%) males and 55(55%) females. There was no statistical difference between caries prevalence in both groups. The most prevalent oral lesions in asthmatics group were geographic tongue 10(10%), fissured tongue 13(13%), chronic atrophic candidiasis13(13%), and in the control group were fissured tongue(11%) and lichenoid reaction(2%). The dental professional must be familiar with all signs and symptoms of this disease in order to offer effective and safe treatment. PMID- 26564299 TI - Laparoscopic resection of gastro-intestinal stromal tumour. AB - Gastro-Intestinal Stromal Tumours are rare tumours, constituting less than 1% of gastrointestinal tumours. They are the most common mesenchymal origin tumours of gastro-intestinal tract. Tyrosine kinase c-kit oncogene mutation is found in all cases. These tumours are sensitive to imatinib. They are usually noted incidentally on endoscopy or present with haematemesis after ulceration. We are reporting the laparoscopic resection of GIST in a 67 year old male who had presented with haematemesis. He was found to have a gastric polyp on endoscopy. Endoscopic ultra-soundshowed the tumour to be arising from the submucosa. Histo pathology showed the tumour to be GIST. Patient is currently undergoing chemotherapy. PMID- 26564300 TI - Acute dystonic reaction due to dexketoprofen trometamol. AB - Dexketoprofentrometamol (DKP), is a tromethamine salt of the water-soluble S enantiomer of ketoprofen. As with all other non-steroidal anti-inflammatory agents, the most common side effect of DKP is gastric complications. In this paper, we report a case of dystonic reaction after intravenous DKP use. A 24-year old man was admitted to our hospital after suffering a leg burn from boiling oil. He had no drug hypersensitivity. An intravenous preparation containing the active ingredient DKP was injected for analgesia, after which the patient experienced an involuntary flexion response in both upper extremities. With a suspected diagnosis of dystonia, biperiden lactate 5 mg/ml was administered via the intramuscular route and the contractions abated within 30 seconds of the injection.As non-steroidal anti-inflammatory agents are commonly used and prescribed in emergency departments, it should be kept in mind that an acute dystonic reaction can develop against one of these agents, DKP. PMID- 26564301 TI - An isolated hyoid bone fracture caused by blunt trauma to the neck. AB - Hyoid bone fractures due to blunt trauma are exceedingly rare. Here, we present an isolated hyoid bone fracture caused by blunt trauma as well as a detailed discussion of the injury and treatment options. A 32-year-old male was admitted to emergency department with odynophagia and severe neck pain. He had been hit in the neck with a metal rod during a fight. Computed tomography scan revealed a fracture on hyoid bone and local swelling of adjacent soft tissues. The patient?'s head was elevated, and ice packs were used to reduce the swelling. Diclofenac sodium and prednisolone were administered. Patient was discharged with a recommendation of out-patient control. Odynophagia, dysphagia and dyspnoea should alert the physician to possible hyoid or laryngeal damage. Fibre optic laryngoscopy and neck CT are important diagnostic steps to reveal a possible life threatening injury. Conservative treatment is usually adequate, and patients rarely require surgical intervention. PMID- 26564302 TI - A rare case of isolated macronodular hepatic tuberculosis (Tuberculous) in an immunocompetent patient. AB - Tuberculosis is one of the most common and well described infectious diseases, with a world wide distribution and a vast spectrum of clinical manifestations. There are three forms of hepatic tuberculosis. Diffuse hepatic involvement with pulmonary or miliary tuberculosis, diffuse hepatic infiltration without recognizable pulmonary involvement is the second form and the third very rare form presents as a focal/local tuberculoma or abscess. In this case report we describe an unusual appearance of macronodular tuberculomas of the liver. PMID- 26564303 TI - The metabolic score: A decision making tool in diabetes care. AB - The heterogeneity of diabetes mellitus, and the various metabolic abnormalities associated with it, are well known. Current management guidelines used to help choose glucose-lowering drugs in diabetes mellitus describe various drug classes in detail, but do not take the overall metabolic profile into consideration. To help physicians choose appropriate oral therapy, we propose a discrete metabolic score, based upon the presence and absence of metabolic comorbidities included in the definition of metabolic syndrome. This communication describes how to choose an appropriate oral antidiabetic drug using such a score. The metabolic score based decision making aid should be able to prove its utility in all health care settings, especially resource constrained societies. PMID- 26564304 TI - Pre-conception management of diabetes. AB - Pre-conception management of diabetes implies the optimization of all biological, social, and psychological factors, prior to conception, in a woman with preexisting type 1 or type 2 diabetes. Pre-conception management includes appropriate counseling, investigations, glycaemic and supportive management. This brief communication encapsulates the essential features of pre-conception management. PMID- 26564305 TI - Increased incidence of measles in vaccinated population of Pakistan. PMID- 26564306 TI - A rare cause of ileus in an infant: a case of gossypiboma. PMID- 26564307 TI - An audit of clinical laboratory data of 25 [OH]D at Aga Khan University as reflecting vitamin D deficiency in Pakistan. AB - OBJECTIVE: To estimate the burden of Vitamin D deficiency in people from different geographical areas of Pakistan. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised specimens of subjects tested for 25-hydroxy D at the clinical laboratory between September 2010 and September 2011. Serum samples received from the phlebotomy centres all over Pakistan and the main laboratory in Karachi were included. SPSS 19 was used for statistical analysis. RESULTS: Of the 60937 specimens in the study, 18721(30.7%) related to men. The overall mean age was 40.5+/-19.7 years, and median 25-hydroxy D level was 13.5ng/ml (interquartile range: 25.1-7.4 ng/ml).Overall, mean log 25-hydroxy D was 1.14+/-0.39ng/ml (median: 13.5ng/ml; interquartile range: 25.1-7.4 ng/ml). Out of the total, 40279(66.1%) subjects were vitamin D-deficient. CONCLUSIONS: Vitamin D deficiency was common among the subjects. PMID- 26564308 TI - Takotsubo cardiomyopathy (Broken heart syndrome). AB - Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study. PMID- 26564309 TI - Prediction model to predict critical weight loss in patients with head and neck cancer during (chemo)radiotherapy. AB - OBJECTIVES: Patients with head and neck cancer (HNC) frequently encounter weight loss with multiple negative outcomes as a consequence. Adequate treatment is best achieved by early identification of patients at risk for critical weight loss. The objective of this study was to detect predictive factors for critical weight loss in patients with HNC receiving (chemo)radiotherapy ((C)RT). MATERIALS AND METHODS: In this cohort study, 910 patients with HNC were included receiving RT (+/-surgery/concurrent chemotherapy) with curative intent. Body weight was measured at the start and end of (C)RT. Logistic regression and classification and regression tree (CART) analyses were used to analyse predictive factors for critical weight loss (defined as >5%) during (C)RT. Possible predictors included gender, age, WHO performance status, tumour location, TNM classification, treatment modality, RT technique (three-dimensional conformal RT (3D-RT) vs intensity-modulated RT (IMRT)), total dose on the primary tumour and RT on the elective or macroscopic lymph nodes. RESULTS: At the end of (C)RT, mean weight loss was 5.1+/-4.9%. Fifty percent of patients had critical weight loss during (C)RT. The main predictors for critical weight loss during (C)RT by both logistic and CART analyses were RT on the lymph nodes, higher RT dose on the primary tumour, receiving 3D-RT instead of IMRT, and younger age. CONCLUSION: Critical weight loss during (C)RT was prevalent in half of HNC patients. To predict critical weight loss, a practical prediction tree for adequate nutritional advice was developed, including the risk factors RT to the neck, higher RT dose, 3D-RT, and younger age. PMID- 26564310 TI - Swallowing outcome measures in head and neck cancer--How do they compare? AB - OBJECTIVES: Dysphagia is a common and debilitating side effect of chemoradiotherapy. Assessment is difficult; swallowing is multifactorial and studies choose from a range of dysphagia assessments. This study intended to investigate the relationship between swallowing assessments of dysphagia in a cohort of patients and to evaluate whether clinical swallowing measures can predict patient reported swallowing outcomes. MATERIALS AND METHODS: One hundred and seventy-three head and neck cancer patients from two teaching hospitals were recruited prospectively over 25 months. At three months follow-up patients were assessed using Rosenbeck's Penetration-Aspiration Scale (PAS), The 100 ml Water Swallow Test (WST), The Performance Status Scale: Normalcy of Diet and the MD Anderson Dysphagia Inventory (MDADI). RESULTS: The highest correlation was observed between the MDADI and Normalcy of Diet (rho 0.68) and the lowest between the MDADI and the PAS (rho 0.34). Using multiple regression the PAS and WST accounted for 44% of the variance in the MDADI scores (R2 = 0.44, F = 37.8, p < 0.001). On stepwise regression, the model only retained the Normalcy of Diet scores (R2 = 0.42, F=107.9, p < 0.001). Separating the PAS into subgroups, those with no penetration or aspiration on the PAS scored significantly higher on the MDADI (p = <0.001). CONCLUSION: Patient reported swallowing outcomes were strongly aligned with diet restrictions but poorly aligned with clinical assessment. The WST, however, was more correlated than the PAS score, representing a more functional assessment. Clinical dysphagia, associated with significant morbidity, and patient reported dysphagia related to quality of life are not interchangeable and must be measured separately. PMID- 26564311 TI - Simultaneous determination of water-soluble whitening ingredients and adenosine in different cosmetic formulations by high-performance liquid chromatography coupled with photodiode array detection. AB - OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mm KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R(2) >= 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42 104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics. PMID- 26564312 TI - Designing Photoelectrodes for Photocatalytic Fuel Cells and Elucidating the Effects of Organic Substrates. AB - Photocatalytic fuel cells (PFCs) are constructed from anodized photoanodes with the aim of effectively converting organic materials into solar electricity. The syntheses of the photoanodes (TiO2 , WO3 , and Nb2 O5 ) were optimized using the statistical 2(k) factorial design. A systematic study was carried out to catalog the influence of eleven types of organic substrate on the photocurrent responses of the photoanodes, showing dependence on the adsorption of the organic substrates and on the associated photocatalytic degradation mechanisms. Strong adsorbates, such as carboxylic acids, generated high photocurrent enhancements. Simple and short-chained molecules, such as formic acid and methanol, are the most efficient in the corresponding carboxylic acid and alcohol groups as a result of their fast degradation kinetics. The TiO2 -based PFC yielded the highest photocurrent and obtainable power, whereas the Nb2 O5 -based PFC achieved the highest open-circuit voltage, which is consistent with its most negative Fermi level. PMID- 26564313 TI - The potential diagnostic power of circulating tumor cell analysis for non-small cell lung cancer. AB - In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC. PMID- 26564314 TI - Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium dependent and -independent relaxation of rat aortic rings. AB - AIM: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. METHODS: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay. RESULTS: Application of brazilin (10-100 MUmol/L) dose dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51+/-5.6 and 79.79+/-4.57 MUmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. CONCLUSION: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels. PMID- 26564315 TI - Pro forma for ultrasound reporting in suspected abnormally invasive placenta (AIP): an international consensus. PMID- 26564316 TI - Non-Cell-Autonomous Regulation of Cellular Senescence in Cancer. AB - Cellular senescence is a permanent growth arrest that is broadly recognized to act as a barrier against tumorigenesis. Senescence is predominant in premalignant tumors, and senescence escape is thought to be required for tumor progression. Importantly, evidences indicate that cell-autonomous mechanisms, such as genetic alterations or therapeutic interventions targeting specific genetic pathways, can affect the senescence response in cancer. Nevertheless, new findings have emerged in the last few years that indicate a fundamental role for the tumor microenvironment in the regulation of cellular senescence. Indeed, cytokines belonging to the senescent secretome, as well as tumor-infiltrating immune subsets, have been described to modulate the senescence response in tumors. Such evidence demonstrates that senescence initiation also relies on non-cell autonomous mechanisms, which are discussed in the present review. PMID- 26564317 TI - Oxygen-Promoted Suzuki-Miyaura Reaction for Efficient Construction of Biaryls. AB - As one of the most powerful and versatile methods for the construction of carbon carbon bonds, the Suzuki-Miyaura cross-coupling reaction has attracted great attention over the past three decades. In recent years, a huge amount of interest has been focused on the development of ligand-free Suzuki-Miyaura reaction systems, which have the advantages of low cost, mild reaction conditions, and easy operation. So far, a number of ligand-free Suzuki-Miyaura reaction systems have been developed by using simple palladium salts, nanopalladium, or supported palladium catalysts. In this account, we will review our recent research on the oxygen-promoted ligand-free Suzuki-Miyaura reaction. Interestingly, the oxygen promoting effect has been observed in different reaction media, including polyethylene glycol, organic/water mixed solvents and pure water. The oxygen promoted reaction systems demonstrate high efficiency for the construction of biaryls. PMID- 26564319 TI - Evaluation of 6-11C-Methyl-m-Tyrosine as a PET Probe for Presynaptic Dopaminergic Activity: A Comparison PET Study with beta-11C-l-DOPA and 18F-FDOPA in Parkinson Disease Monkeys. AB - We recently developed a novel PET probe, 6-(11)C-methyl-m-tyrosine ((11)C 6MemTyr), for quantitative imaging of presynaptic dopamine synthesis in the living brain. In the present study, (11)C-6MemTyr was compared with beta-(11)C-l DOPA and 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) in the brains of normal and Parkinson disease (PD) model monkeys (Macaca fascicularis). METHODS: PD model monkeys were prepared by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and (11)C-beta-CFT was applied to assess neuronal damage as dopamine transporter (DAT) availability. (11)C-6MemTyr, beta-(11)C-l-DOPA, or (18)F-FDOPA was injected with and without carbidopa, a specific inhibitor of peripheral aromatic L-amino acid decarboxylase. In normal and PD monkeys, the dopamine synthesis rates calculated using PET probes were analyzed by the correlation plot with DAT availability in the striatum. RESULTS: In normal monkeys, whole-brain uptake of beta-(11)C-l-DOPA and (18)F-FDOPA were significantly increased by carbidopa at the clinical dose of 5 mg/kg by mouth. In contrast, (11)C-6MemTyr was not affected by carbidopa at this dose, and the metabolic constant value of (11)C-6MemTyr in the striatum was significantly higher than those of the other 2 PET probes. Significant reduction of the presynaptic DAT availability in the striatum was detected in MPTP monkeys, and correlation analyses demonstrated that (11)C-6MemTyr could detect dopaminergic damage in the striatum with much more sensitivity than the other PET probes. CONCLUSION: (11)C-6MemTyr is a potential PET probe for quantitative imaging of presynaptic dopamine activity in the living brain with PET. PMID- 26564318 TI - Dynamic In Vivo SPECT Imaging of Neural Stem Cells Functionalized with Radiolabeled Nanoparticles for Tracking of Glioblastoma. AB - There is strong clinical interest in using neural stem cells (NSCs) as carriers for targeted delivery of therapeutics to glioblastoma. Multimodal dynamic in vivo imaging of NSC behaviors in the brain is necessary for developing such tailored therapies; however, such technology is lacking. Here we report a novel strategy for mesoporous silica nanoparticle (MSN)-facilitated NSC tracking in the brain via SPECT. METHODS: (111)In was conjugated to MSNs, taking advantage of the large surface area of their unique porous feature. A series of nanomaterial characterization assays was performed to assess the modified MSN. Loading efficiency and viability of NSCs with (111)In-MSN complex were optimized. Radiolabeled NSCs were administered to glioma-bearing mice via either intracranial or systemic injection. SPECT imaging and bioluminescence imaging were performed daily up to 48 h after NSC injection. Histology and immunocytochemistry were used to confirm the findings. RESULTS: (111)In-MSN complexes show minimal toxicity to NSCs and robust in vitro and in vivo stability. Phantom studies demonstrate feasibility of this platform for NSC imaging. Of significance, we discovered that decayed (111)In-MSN complexes exhibit strong fluorescent profiles in preloaded NSCs, allowing for ex vivo validation of the in vivo data. In vivo, SPECT visualizes actively migrating NSCs toward glioma xenografts in real time after both intracranial and systemic administrations. This is in agreement with bioluminescence live imaging, confocal microscopy, and histology. CONCLUSION: These advancements warrant further development and integration of this technology with MRI for multimodal noninvasive tracking of therapeutic NSCs toward various brain malignancies. PMID- 26564320 TI - Uncertainty Quantification in Internal Dose Calculations for Seven Selected Radiopharmaceuticals. AB - Dose coefficients of radiopharmaceuticals have been published by the International Commission on Radiological Protection (ICRP) and the MIRD Committee but without information concerning uncertainties. The uncertainty information of dose coefficients is important, for example, to compare alternative diagnostic methods and choose the method that causes the lowest patient exposure with appropriate and comparable diagnostic quality. For the study presented here, an uncertainty analysis method was developed and used to calculate the uncertainty of the internal doses of 7 common radiopharmaceuticals. METHODS: On the basis of the generalized schema of dose calculation recommended by the ICRP and MIRD Committee, an analysis based on propagation of uncertainty was developed and applied for 7 radiopharmaceuticals. The method takes into account the uncertainties contributed from pharmacokinetic models and the so-called S values derived from several voxel computational phantoms previously developed at Helmholtz Zentrum Munchen. Random and Latin hypercube sampling techniques were used to sample parameters of pharmacokinetic models and S values, and the uncertainties of absorbed doses and effective doses were calculated. RESULTS: The uncertainty factors (square root of the ratio between 97.5th and 2.5th percentiles) for organ-absorbed doses are in the range of 1.1-3.3. Uncertainty values of effective doses are lower in comparison to absorbed doses, the maximum value being approximately 1.4. The ICRP reference values showed a deviation comparable to the effective dose calculated in this study. CONCLUSION: A general statistical method was developed for calculating the uncertainty of absorbed doses and effective doses for 7 radiopharmaceuticals. The dose uncertainties can be used to further identify the most important parameters in the dose calculation and provide reliable dose coefficients for risk analysis of the patients in nuclear medicine. PMID- 26564321 TI - DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy. AB - The aim of the study was to investigate DNA double-strand break (DSB) formation and its correlation to the absorbed dose to the blood in patients with surgically treated differentiated thyroid cancer undergoing their first radioiodine therapy for remnant ablation. METHODS: Twenty patients were included in this study. At least 7 peripheral blood samples were obtained before and between 0.5 and 120 h after administration of radioiodine. From the time-activity curves of the blood and the whole body, residence times for the blood self-irradiation and the irradiation from the whole body were determined. Peripheral blood lymphocytes were isolated, ethanol-fixed, and subjected to immunofluorescence staining for colocalizing gamma-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was analyzed as a function of the absorbed dose to the blood and compared with an in vitro calibration curve for (131)I and (177)Lu established previously in our institution. RESULTS: The average number of radiation-induced foci (RIF) per cell increased over the first 3 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 2 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time points, RIF numbers diminished, along with dropping dose rates, indicating progression of DNA repair. Individual patient data were characterized by a linear dose-dependent increase and a biexponential response function describing a fast and a slow repair component. CONCLUSION: With the experimental results and model calculations presented in this work, a dose response relationship is demonstrated, and an analytic function describing the time course of the in vivo damage response after internal irradiation of patients with (131)I is established. PMID- 26564324 TI - Therapeutic Nuclear Medicine. PMID- 26564322 TI - 68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI. AB - Pheochromocytomas/paragangliomas overexpress somatostatin receptors, and recent studies have already shown excellent results in the localization of sympathetic succinate dehydrogenase complex, subunit B, mutation-related metastatic pheochromocytomas/paragangliomas using (68)Ga-DOTATATE PET/CT. Therefore, the goal of our study was to assess the clinical utility of this functional imaging modality in parasympathetic head and neck paragangliomas (HNPGLs) compared with anatomic imaging with CT/MRI and other functional imaging modalities, including (18)F-fluorohydroyphenylalanine ((18)F-FDOPA) PET/CT, currently the gold standard in the functional imaging of HNPGLs. METHODS: (68)Ga-DOTATATE PET/CT was prospectively performed in 20 patients with HNPGLs. All patients also underwent (18)F-FDOPA PET/CT, (18)F-FDG PET/CT, and CT/MRI, with 18 patients also undergoing (18)F-fluorodopamine ((18)F-FDA) PET/CT. (18)F-FDOPA PET/CT and CT/MRI served as the imaging comparators. RESULTS: Thirty-eight lesions in 20 patients were detected, with (18)F-FDOPA PET/CT identifying 37 of 38 and CT/MRI identifying 23 of 38 lesions (P < 0.01). All 38 and an additional 7 lesions (P = 0.016) were detected on (68)Ga-DOTATATE PET/CT. Significantly fewer lesions were identified by (18)F-FDG PET/CT (24/38, P < 0.01) and (18)F-FDA PET/CT (10/34, P < 0.01). CONCLUSION: (68)Ga-DOTATATE PET/CT identified more lesions than other imaging modalities. With the results of the present study, and the increasing availability and use of DOTA analogs in the therapy of neuroendocrine tumors, we expect that (68)Ga-DOTATATE PET/CT will become the preferred functional imaging modality for HNPGLs in the near future. PMID- 26564325 TI - SUVpeak Performance in Lung Cancer: Comparison to Average SUV from the 40 Hottest Voxels. AB - The performance of an average SUV over a 1-mL-volume sphere within an (18)F-FDG positive lesion resulting in the highest possible value (SUVpeakW) was compared with that of an average SUV computed from the 40 hottest voxels, irrespective of their location within the lesion (SUVmax-40). METHODS: Dynamic PET performed in 20 lung cancer lesions yielded for each SUV metric its mean value, relative measurement error, and repeatability (MEr-R). RESULTS: SUVpeakW mean value was significantly 9.66% lower than that of SUVmax-40 (P < 0.0001). SUVpeakW and SUVmax-40 MEr-R were significantly lower than the MEr-R of SUVmax (the hottest voxel): 9.35%-13.21% and 8.84%-12.49% versus 13.86%-19.59%, respectively, (95% confidence limit; P < 0.0001). Although being marginal, SUVpeakW MEr-R was not significantly greater than SUVmax-40 MEr-R (P = 0.086). CONCLUSION: SUVmax-40 is more likely to represent the most metabolically active portions of tumors than SUVpeakW, with close variability performance. PMID- 26564323 TI - First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease. AB - Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. METHODS: CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. RESULTS: A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CONCLUSION: CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma. PMID- 26564326 TI - Diagnostic Reference Levels of CT Radiation Dose in Whole-Body PET/CT. AB - The role of CT in PET/CT imaging includes acquisition techniques for diagnostic, anatomic localization, and attenuation correction purposes. Diagnostic reference levels of the volumetric CT dose index (CTDIvol) are available for dedicated CT procedures on selected body regions, but similar reference levels for whole-body CT used in PET/CT examinations are limited. This work reports CTDIvol values from sites that conduct whole-body oncologic PET/CT examinations and participated in the scanner validation program of the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network. METHODS: From 2010 to 2014, a total of 154 sites submitted CT acquisition parameters used in their clinical (18)F-FDG PET/CT oncology protocols. From these parameters, the CTDIvol was estimated using the ImPACT CTDI dosimetry tables. Histograms of CTDIvol values were created for each year, and descriptive statistics, including mean, median, and 75th percentile, were reported. Repeated-measures ANOVA was performed to determine whether significant differences occurred between reporting years. RESULTS: A wide range of technical parameters was reported, most notably in tube current. Between 2010 and 2014, the median CTDIvol ranged from 4.9 to 6.2 mGy and the 75th percentile from 9.7 to 10.2 mGy. There was no significant change in CTDIvol between reporting years (repeated-measures ANOVA, P = 0.985). CONCLUSION: The 75th percentile CTDIvol reported in this work was 9.8 mGy averaged over all reporting years. These data provide a resource for establishing CTDIvol reference values specific to performing CT in PET/CT whole-body examinations. The wide ranges of CT acquisition parameters reported by sites suggest that CTDIvol reference levels may be beneficial for optimization of CT protocols. PMID- 26564327 TI - [Association between food and nutrition insecurity with cardiometabolic risk factors in childhood and adolescence: a systematic review]. AB - OBJECTIVE: To address the association between food and nutrition insecurity and cardiometabolic risk factors in childhood and adolescence. DATA SOURCE: Articles were selected from the Medline, Lilacs and SciELO databases with no publication date limit, involving children and adolescents, using the descriptors: food and nutrition security, diabetes mellitus, hypertension, metabolic syndrome, stress and dyslipidemia. The terms were used in Portuguese, English and Spanish. The search was carried out systematically and independently by two reviewers. DATA SYNTHESIS: Exposure to food insecurity during childhood and adolescence ranged from 3.3% to 82% in the selected publications. Exposure to food insecurity was associated with stress, anxiety, greater chance of hospitalization, nutritional deficiencies, excess weight and inadequate diets with reduced intake of fruits and vegetables and increased consumption of refined carbohydrates and fats. CONCLUSIONS: Food and nutrition insecurity was associated with the presence of cardiometabolic risk factors in the assessed publications. Childhood and adolescence constitute a period of life that is vulnerable to food insecurity consequences, making it extremely important to ensure the regular and permanent access to food. Because this is a complex association, some difficulties are found, such as the synergy between risk factors, the assessment of heterogeneous groups and extrapolation of data to other populations, in addition to the influence of environmental factors. PMID- 26564328 TI - [Acute effect of vigorous aerobic exercise on the inhibitory control in adolescents]. AB - OBJECTIVE: To assess the acute effect of vigorous aerobic exercise on the inhibitory control in adolescents. METHODS: Controlled, randomized study with crossover design. Twenty pubertal individuals underwent two 30-minute sessions: 1) aerobic exercise session performed between 65%-75% of heart rate reserve, divided into 5minutes of warm-up, 20minutes at the target intensity and 5minutes of cool down; and 2) control session watching a cartoon. Before and after the sessions, the computerized Stroop test-TestinpacsTM was applied to evaluate the inhibitory control. Reaction time (ms) and errors (n) were recorded. RESULTS: The control session reaction time showed no significant difference. On the other hand, the reaction time of the exercise session decreased after the intervention (p<0.001). The number of errors made at the exercise session were lower than in the control session (p=0.011). Additionally, there was a positive association between reaction time (Delta) of the exercise session and age (r(2)=0.404, p=0.003). CONCLUSIONS: Vigorous aerobic exercise seems to promote acute improvement in the inhibitory control in adolescents. The effect of exercise on the inhibitory control performance was associated with age, showing that it was reduced at older age ranges. PMID- 26564329 TI - Services Receipt Following Veteran Outpatients' Positive Screen for Homelessness. AB - INTRODUCTION: The Veterans Health Administration seeks to reduce homelessness among Veterans by identifying, and providing prevention and supportive services to, patients with housing concerns. The objectives of this study were to assess the proportion of Veterans Health Administration patients who received homeless or social work services within 6 months of a positive screen for homelessness or risk in the Veterans Health Administration and the demographic and clinical characteristics that predicted services utilization. METHODS: Data were from a cohort of 27,403 Veteran outpatients who screened positive for homelessness or risk between November 1, 2012 and January 31, 2013. During 2013, AORs were calculated using a mixed-effects logistic regression to estimate the likelihood of patients' receipt of VHA homeless or social work services based on demographic and clinical characteristics. RESULTS: The majority of patients received services within 6 months post-screening; predictors of services utilization varied by gender. Among women, diagnosis of drug abuse and psychosis predicted receipt of services, being unmarried increased the odds of using services among those screening positive for homelessness, and a diagnosis of post-traumatic stress disorder increased the odds of receiving services for at-risk women. Among men, being younger, unmarried, not service-connected/Medicaid-eligible, and having a medical or behavioral health condition predicted receipt of services. CONCLUSIONS: Receipt of housing support services among Veterans post-homelessness screening differs by patient demographic and clinical characteristics. Future research should investigate the role that primary and secondary prevention interventions play in Veterans' resolution of risk for homelessness and experience of homelessness. PMID- 26564330 TI - An importance-performance analysis of hospital information system attributes: A nurses' perspective. AB - PURPOSE: Health workers have numerous concerns about hospital IS (HIS) usage. Addressing these concerns requires understanding the system attributes most important to their satisfaction and productivity. Following a recent HIS implementation, our objective was to identify priorities for managerial intervention based on user evaluations of the performance of the HIS attributes as well as the relative importance of these attributes to user satisfaction and productivity outcomes. PROCEDURES: We collected data along a set of attributes representing system quality, data quality, information quality, and service quality from 154 nurse users. Their quantitative responses were analysed using the partial least squares approach followed by an importance-performance analysis. Qualitative responses were analysed using thematic analysis to triangulate and supplement the quantitative findings. MAIN FINDINGS: Two system quality attributes (responsiveness and ease of learning), one information quality attribute (detail), one service quality attribute (sufficient support), and three data quality attributes (records complete, accurate and never missing) were identified as high priorities for intervention. CONCLUSIONS: Our application of importance-performance analysis is unique in HIS evaluation and we have illustrated its utility for identifying those system attributes for which underperformance is not acceptable to users and therefore should be high priorities for intervention. PMID- 26564331 TI - Applicability of citronella oil (Cymbopogon winteratus) for the prevention of mosquito-borne diseases in the rural area of Tikapur, far-western Nepal. AB - INTRODUCTION: Mosquito-borne diseases are a serious global problem, particularly in tropical and sub-tropical countries such as Nepal. Citronella oil is a natural mosquito repellent as well as a local fragrance in Nepal, which is accessible at very low cost because citronella plants are widely cultivated in rural areas of the Terai belt in Nepal. This study was conducted using a real-life randomized controlled pilot trial to confirm the effectiveness and applicability of locally produced citronella oil as a mosquito repellent for the prevention of mosquito borne diseases in Nepal. METHODS: A repellency activity test was performed with 100% citronella oil (Cymbopogon winteratus) from April to May 2013 in the Tikapur Municipality of the Kailali district, Nepal. The test was divided into two trials: an indoor exposure (IE) test (N=101) and an outdoor exposure (OE) test (N=140) from 5.00 pm to 7.00 pm. Each trial contained an experimental citronella oil-applied group and a non-applied (control) group. The outcome measures were the protective effect of citronella oil against mosquitoes, the number of mosquito bites, the repellency percentage, the smell satisfaction and the irritation level. RESULTS: Experimental group had a significant protective effect against mosquito bites in IE (96.5%, n=57) and OE (95.7%, n=70) tests compared to the control group in IE (29.5%, n=44) and OE (28.6%, n=70) tests (experimental vs control groups, p<0.001). The repellency percentage for the OE test was 96.7%. In the smell satisfaction test (n=127), most of the participants responded with high satisfaction: 'good' (67.7%), 'very good' (16.5%), 'bad' (13.4%) and 'very bad' (2.4%). IE and OE tests showed similar satisfaction levels in each category. In the irritation level test (n=127), 87.4% and 12.6% responded with no irritation and slight irritation, respectively. There were no reports of moderate or severe irritation. CONCLUSIONS: The topical application of citronella oil can be employed as an easily-available, affordable and effective alternative mosquito repellent to prevent mosquito-borne diseases in rural areas such as Tikapur, Nepal. PMID- 26564332 TI - Controllable Synthesis and Surface Wettability of Flower-Shaped Silver Nanocube Organosilica Hybrid Colloidal Nanoparticles. AB - Synthesis of hybrid colloidal particles with complex and hierarchical structures is attracting much interest theoretically and technically in recent years, but still remains a tremendous challenge. Here, we present a mild and controllable wet-chemical method for the synthesis of silver nanocube (Ag NC)-organosilica hybrid particles with finely tuned numbers (with one, two, three, four, five, or six) and sizes of organosilica petals, by simply controlling the affinity with Ag NC/nature, amount, and prehydrolysis process of alkoxysilanes. The morphologies of hybrid colloidal particles have an obvious influence on the surface wettability of the hybrid particle-based films. More and larger organosilica petals can increase the surface hydrophobicity of the hybrid particle-based films. PMID- 26564333 TI - Inoculation of new rhizobial isolates improve nutrient uptake and growth of bean (Phaseolus vulgaris) and arugula (Eruca sativa). AB - BACKGROUND: In the current agricultural model, the massive use of chemical fertilizer causes environmental and economic losses. Inoculation of plant-growth promoting (PGP) nitrogen-fixing bacteria is an alternative to the use of nitrogen, phosphorus and potassium fertilizers. In this study, rhizobia strains isolated from common bean (Phaseolus vulgaris) root nodules were evaluated in an effort to identify an efficient nitrogen-fixing rhizobia strain able to improve bean germination and growth. RESULTS: Common bean plants were collected from seven sites in southern Brazil, and 210 native rhizobia isolates were obtained. Evaluation of PGP traits showed that most of the rhizobia isolates were non siderophore producers and weak indolic compounds producers. Under laboratory conditions, rhizobia isolates E15 (Rhizobium leguminosarum) and L5 (Rhizobium radiobacter) increase germination percentage, length, and dry weight of common bean and arugula (Eruca sativa) seedlings. Under greenhouse conditions, common bean plants inoculated with the rhizobia isolates VC28 and L15 (both Rhizobium fabae) presented the highest nodule number and shoot dry matter, while VC28 also presented the highest values of shoot nitrogen and potassium. Isolate L17 presented highly effective N fixation, even with reduced nodulation. CONCLUSION: These new rhizobia isolates are attractive PGP alternatives to chemical fertilizers. (c) 2015 Society of Chemical Industry. PMID- 26564334 TI - Vitamin D modulates adipose tissue biology: possible consequences for obesity? AB - Cross-sectional studies depict an inverse relationship between vitamin D (VD) status reflected by plasma 25-hydroxy-vitamin D and obesity. Furthermore, recent studies in vitro and in animal models tend to demonstrate an impact of VD and VD receptor on adipose tissue and adipocyte biology, pointing to at least a part causal role of VD insufficiency in obesity and associated physiopathological disorders such as adipose tissue inflammation and subsequent insulin resistance. However, clinical and genetic studies are far less convincing, with highly contrasted results ruling out solid conclusions for the moment. Nevertheless, prospective studies provide interesting data supporting the hypothesis of a preventive role of VD in onset of obesity. The aim of this review is to summarise the available data on relationships between VD, adipose tissue/adipocyte physiology, and obesity in order to reveal the next key points that need to be addressed before we can gain deeper insight into the controversial VD-obesity relationship. PMID- 26564335 TI - Heterometallic Fe(III) /K Coordination Polymer with a Wide Thermal Hysteretic Spin Transition at Room Temperature. AB - The anionic Fe(III) complex exhibiting cooperative spin transition with a wide thermal hysteresis near room temperature, K[Fe(5-Brthsa)2 ] (5-Brthsa-H2 =5 bromosalicylaldehyde thiosemicarbazone), is reported. The hysteresis (Delta=69 K in the first cycle) shows a one-step transition in heating mode and a two-step transition in cooling mode. X-ray structure analysis showed that the coexistence of hydrogen bond and cation-pi interactions, as well as alkali metal coordination bonds, to give 2D coordination polymer structure. This result is contrary to previous reports of broad thermal hysteresis induced by coordination bonds of Fe(II) spin crossover coordination polymers (with 1D/3D structures), and by strong intermolecular interactions in the molecular packing through pi-pi stacking or hydrogen-bond networks. As a consequence, the importance, or the very good suitability of alkali metal-based coordination bonds and cation-pi interactions for communicating cooperative interactions in spin-crossover (SCO) compounds must be reconsidered. PMID- 26564336 TI - Together we change: An ambitious blueprint for primary healthcare in Flanders. PMID- 26564337 TI - Co-Doping of Activated Graphene for Synergistically Enhanced Electrocatalytic Oxygen Reduction Reaction. AB - Doping of graphene has emerged as a key strategy to improve the electrocatalytic performance of the oxygen reduction reaction (ORR). Activated graphene co-doped with iodine and nitrogen atoms (NIG) was developed in this work using a facile scalable approach. The onset potential, current density, and four-electron reduction pathway of the newly developed catalyst were significantly improved. The charge-transfer resistance of co-doped NIG was found to be much lower than nitrogen-doped graphene (NG); furthermore, the stability of NIG and its resistance to methanol crossover were also improved. The synergistically enhanced ORR performance of NIG was found to be a result of a high strain and size advantage of the larger iodine atom clusters (compared to nitrogen), which facilitate the simultaneous enrichment of anode electrons and O2 and H2 O molecule transport at catalytic sites, inducing four-electron transfer in a single step. These results are promising for application in alkaline fuel cells. PMID- 26564338 TI - Taking action. PMID- 26564339 TI - Dental education: The next generation. PMID- 26564340 TI - Case report: A bridge too far! PMID- 26564341 TI - In practice: Is lipstick oral health? PMID- 26564342 TI - Case report: Haematomas. PMID- 26564343 TI - Supporting AMR awareness. PMID- 26564345 TI - An update on sugar. PMID- 26564347 TI - FGDP(UK) response to Nordic Institute research into restorations and decay. PMID- 26564350 TI - Now and then: Student associations. PMID- 26564352 TI - When David met Sara part 1. PMID- 26564353 TI - Fluoridation and hypothyroidism--a commentary on Peckham et al. AB - In many countries around the world community water fluoridation is a key element in the campaign for better dental public health. Its safety and effectiveness have been confirmed through decades of research, and the practice has been strongly endorsed by reputable health authorities. A strong evidence base is critical for the implementation of fluoridation and other public health measures. Health professionals must ensure that the highest quality evidence is promoted, and weak evidence identified and discredited. PMID- 26564354 TI - Managing caries: the need to close the gap between the evidence base and current practice. AB - Underpinned by a changing knowledge of the aetiology of caries and its sequelae, and assisted by established and advancing dental materials, there is growing evidence supporting less invasive management of dental caries based on the principles of minimal intervention dentistry. This narrative review assesses both the evidence and the adoption of less invasive caries management strategies and describes ways in which the gap between evidence and practice might be overcome. While there is increasing data supporting less invasive management of carious lesions, these are not standard in most dental practices worldwide. Usually, clinical studies focused on efficacy as outcome, and did not take into consideration the views and priorities of other stakeholders, such as primary care dentists, educators, patients and those financing services. Involving these stakeholders into study design and demonstrating the broader advantages of new management strategies might improve translation of research into practice. In theory, clinical dentists can rely on a growing evidence in cariology regarding less invasive management options. In practice, further factors seem to impede adoption of these strategies. Future research should address these factors by involving major stakeholders and investigating their prioritised outcomes to narrow or close the evidence gap. PMID- 26564360 TI - Summary of: Understanding emotionally relevant situations in primary dental practice. 2. Reported effects of emotionally charged situations. PMID- 26564361 TI - Summary of: Oral health status of non-phobic and dentally phobic individuals; a secondary analysis of the 2009 Adult Dental Health Survey. PMID- 26564355 TI - Effective anaesthesia of the acutely inflamed pulp: part 2. Clinical strategies. AB - Achieving profound pulpal anaesthesia in a mandibular molar diagnosed with irreversible pulpitis can be argued to be the most testing of dental anaesthetic challenges. Following discussion on the possible reasons for this occurrence in part 1, part 2 outlines the various local anaesthetic techniques that practitioners can use to overcome the acutely inflamed mandibular molar. They should then be able to apply these same principles to help anaesthetise any other tooth presenting with an acutely inflamed pulp. Techniques are discussed in detail along with key variables that have been associated with having an impact on the anaesthetic efficacy. This is to bring to light factors that can aid anaesthetic success as well as dispel common misnomers. PMID- 26564362 TI - Students' perceived stress and perception of barriers to effective study: impact on academic performance in examinations. AB - AIMS: To identify students' perceptions of barriers to effective study and the relationship between these and demographic characteristics, levels of perceived stress and examination performance. MATERIALS AND METHODS: A questionnaire was distributed to first (BDS1) and final year (BDS5) King's College London dental undergraduates, during Spring 2013. Data were collected on students' social and working environment using a Likert scale from zero to four. Levels of perceived stress and end-of-year examination results were collected. Statistical analyses were undertaken using SPSS(r) and Stata(r) software. RESULTS: A response rate of 83.0% (BDS1) and 82.9% (BDS5) was achieved. Social distractions were perceived to hinder study, with median scores of two and three for females and males respectively. The mean perceived stress score differed significantly (p=0.001) between males and females. Difficulties with journey was a significant predictor of perceived stress (p=0.03) as were family responsibilities (p=0.02). Social distractions were significantly related to examination performance (p=0.001). CONCLUSIONS: Social distractions were the barrier most highly rated as hindering effective study. Levels of perceived stress were high and were significantly associated with gender, a difficult journey to university and family responsibilities. Social distractions were significantly related to examination performance; students rating social distractions highly, performed less well. PMID- 26564363 TI - Mitchell's trimmer: Who was Mitchell and what was he trimming? AB - Mitchell's trimmer, also known as an osteo-trimmer, osteocarver or osteocarver #4, is a commonly used instrument in a dental professional's armamentarium. Today the instrument is used in a range of dental specialties; however, its modern use has no association to trimming. This article explores the origin of the Mitchell's trimmer, its intended use and reveals the founder of the renowned instrument. PMID- 26564372 TI - Understanding emotionally relevant situations in primary dental practice. 2. Reported effects of emotionally charged situations. AB - BACKGROUND AND AIMS: Dentistry is widely reported to be a stressful profession. There is a limited body of research relating to the coping strategies used by dentists whilst in clinical situations. This study aims to use qualitative methods to explore the full extent of the coping strategies associated with stressful events in primary dental practice. METHOD: Semi-structured interviews were conducted with 20 dentists within a 50 mile radius of Lincoln. A thematic analysis was conducted on verbatim transcriptions thereby identifying six themes and 35 codes. RESULTS: Participants described both problem-focussed and emotion focussed strategies. The strategies used had a variety of outcomes in the context of use. Most dentists denied that their emotions affected their decision-making, but then proceeded to describe how they were influential. DISCUSSION AND CONCLUSION: Dentists use a wide variety of coping strategies some of which are maladaptive. Training in the development and recognition of appropriate coping decisions would be appropriate as they would, potentially, improve practitioner decision-making and well-being. PMID- 26564373 TI - Oral health status of non-phobic and dentally phobic individuals; a secondary analysis of the 2009 Adult Dental Health Survey. AB - INTRODUCTION: The aim of this study was to conduct an exploration of differences in oral health behaviour and outcome between dentally phobic and non-phobic participants in the UK Adult Dental Health Survey (ADHS, 2009). The null hypotheses for this study were that there are no differences in oral health status of non-phobic and dental phobic individuals. METHODS: The ADHS survey covered the adult population in England, Wales and Northern Ireland and was commissioned by the NHS Information Centre for Health and Social Care (NHS IC). Dental anxiety was defined using the Modified Dental Anxiety (MDAS) with the cut off point set at 19 and above as indicating dental phobia. Descriptive statistics were calculated and the chi-square test was used to compare both groups in terms of their demographics, oral health, oral health-related behaviour and attitudes, and treatment. RESULTS: More women (16.8% [1,023]) than men (7% [344]) reported dental phobia. Generally, people with dental phobia were in routine occupations (648 [47.7%]), single (402 [29.4%]) and with lower educational attainment (858 [80.9%]). They were irregular attendees (798 [58.5%]), had a less restored dentition, increased numbers of one or more teeth with caries (292 [39.9%]), and were more likely to have PUFA (puss, ulceration, fistulae, abscess) scores of one or more (89 [12.2%]) in comparison to the non-phobic group (314 [5.6%]). However, people with and without dental phobia had similar numbers of sound and missing teeth (34.5% of the phobic group had 20 or more sound teeth in comparison to 31.7% of the non-phobic group). There were significant differences (p<0.001) between the phobic group's and non-phobic group's Oral Health Impact Profile-14 (OHIP) and Oral Impacts on Daily Performance (OIDP) scores with phobic participants having generally higher scores. Additionally, the phobic group responded negatively more commonly about their most recent dental treatment in terms of dentists' ability to listen to their concerns, explaining the reasons for their dental care while paying full attention to their needs by treating them with respect and dignity. The difference between the two groups was statistically significant (p<0.001). CONCLUSIONS: Participants reporting dental phobia are mostly females, irregular attendees and have a greater treatment need with increased caries levels. PMID- 26564374 TI - The usefulness of infection biomarkers in patients with febrile neutropenia in the Emergency Department. PMID- 26564375 TI - [Economic impact of nosocomial bacteraemia. A comparison of three calculation methods]. AB - INTRODUCTION: The excess cost associated with nosocomial bacteraemia (NB) is used as a measurement of the impact of these infections. However, some authors have suggested that traditional methods overestimate the incremental cost due to the presence of various types of bias. The aim of this study was to compare three assessment methods of NB incremental cost to correct biases in previous analyses. METHODS: Patients who experienced an episode of NB between 2005 and 2007 were compared with patients grouped within the same All Patient Refined-Diagnosis Related Group (APR-DRG) without NB. The causative organisms were grouped according to the Gram stain, and whether bacteraemia was caused by a single or multiple microorganisms, or by a fungus. Three assessment methods are compared: stratification by disease; econometric multivariate adjustment using a generalised linear model (GLM); and propensity score matching (PSM) was performed to control for biases in the econometric model. RESULTS: The analysis included 640 admissions with NB and 28,459 without NB. The observed mean cost was ?24,515 for admissions with NB and ?4,851.6 for controls (without NB). Mean incremental cost was estimated at ?14,735 in stratified analysis. Gram positive microorganism had the lowest mean incremental cost, ?10,051. In the GLM, mean incremental cost was estimated as ?20,922, and adjusting with PSM, the mean incremental cost was ?11,916. The three estimates showed important differences between groups of microorganisms. CONCLUSIONS: Using enhanced methodologies improves the adjustment in this type of study and increases the value of the results. PMID- 26564376 TI - Long-Term Outcomes of Carotid Endarterectomy and Carotid Artery Stenting for Carotid Artery Stenosis: Real-World Status in Japan. AB - BACKGROUND AND PURPOSE: We investigated long-term outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in our institute to evaluate the outcomes of real-world practice in Japan. METHODS: Between August 2006 and July 2013, 203 consecutive carotid revascularizations with either CEA or CAS were performed in our institute. The initial treatment was regarded as the starting point in the cases of the patients who received treatment by bilateral carotid artery stenosis or retreatment. We assessed the long-term outcomes with survival analyses. RESULTS: A total of 182 patients (CEA 111, CAS 71), including 86 symptomatic patients, were included in the current study with a mean follow-up period of 42.9 months. The periprocedural stroke/death/myocardial infarction (MI) rate was 3.6% for CEA and 5.6% for CAS groups (P = .71). Estimates of the 4-year event-free rate from the primary end point (the composite of any stroke, death, or MI within 30 days, and any ipsilateral stroke thereafter) using competing risk analysis were 3.6% for CEA and 7.1% for CAS (P = .156). Kaplan-Meier estimates of the 4-year event-free rate from the secondary end point (the composite of any stroke, death, or MI within 30 days, and any stroke or death thereafter) were 13.8% for CEA and 19.1% for CAS (P = .072). Age was the only significant predictor for the primary end point. Both age and CAS were significant predictors for the secondary end point. CONCLUSIONS: The current study on real-world practices demonstrated perioperative and long-term outcomes that were comparable to previous major studies of large numbers of patients. PMID- 26564377 TI - Chemical constituents of essential oil of endemic Rhanterium suaveolens Desf. growing in Algerian Sahara with antibiofilm, antioxidant and anticholinesterase activities. AB - Twenty compounds were detected in the essential oil of Rhanterium suaveolens representing 98.01% of the total oil content. Perillaldehyde (45.79%), caryophyllene oxide (24.82%) and beta-cadinol (5.61%) were identified as the main constituents. In beta-carotene-linoleic acid assay, both the oil and the methanol extract exhibited good lipid peroxidation inhibition activity, with IC50 values of 17.97 +/- 5.40 and 11.55 +/- 3.39 MUg/mL, respectively. In DPPH and CUPRAC assays, however, the methanol extract exhibited a good antioxidant activity. The highest antibiofilm activity has been found 50.30% against Staphylococcus epidermidis (MU 30) at 20 MUg/mL for essential oil and 58.34% against Micrococcus luteus (NRRL B-4375) at 25 mg/mL concentration for methanol extract. The in vitro anticholinesterase activity of methanol extract showed a moderate acetylcholinesterase inhibitory (IC50 = 168.76 +/- 0.62 MUg/mL) and good butyrylcholinesterase inhibitory (IC50 = 54.79 +/- 1.89 MUg/mL) activities. The essential oil was inactive against both enzymes. PMID- 26564378 TI - Is pelvic organ support different between young nulliparous African and Caucasian women? AB - OBJECTIVE: There seems to be substantial variation in the prevalence of pelvic floor disorders between different ethnic groups. This may be due partially to differences in pelvic floor structure and functional anatomy. To date, data on this issue are sparse. The aim of this study was to compare hiatal dimensions, pelvic organ descent and levator biometry in young, healthy nulliparous Caucasian and African women. METHODS: Healthy nulliparous non-pregnant volunteers attending a local nursing school in Uganda were invited to participate in this study during two fistula camps. All volunteers underwent a simple physician-administered questionnaire and a four-dimensional translabial ultrasound examination. Offline analysis was performed to assess hiatal dimensions, pelvic organ descent, levator muscle thickness and area. To compare findings with those obtained in nulliparous non-pregnant Caucasians, we retrieved the three-dimensional/four-dimensional ultrasound volume datasets of a previously published study. RESULTS: The dataset of 76 Ugandan and 49 Caucasian women was analyzed. The two groups were not matched but they were comparable in age and body mass index. All measurements of hiatal dimensions and pelvic organ descent were significantly higher among the Ugandans (all P <= 0.01); however, muscle thickness and area were not significantly different between the two groups. CONCLUSIONS: Substantial differences between Caucasian and Ugandan non-pregnant nulliparae were identified in this study comparing functional pelvic floor anatomy. It appears likely that these differences in functional anatomy are at least partly genetic in nature. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26564379 TI - Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. AB - The research field of extracellular vesicles (EVs), such as microparticles and exosomes, is growing exponentially. The goal of this review is to provide an overview of recent developments relevant to the readers of the Journal of Thrombosis and Haemostasis. We will discuss nomenclature, the presence of EVs in fluids, methods of isolation and detection, and emerging clinical implications. Although research on EVs has been performed within the ISTH for over a decade, most of the recent research on EVs has been brought together by the International Society on Extracellular Vesicles (ISEV). To achieve an overview of recent developments, the information provided in this review comes not only from publications, but also from latest meetings of the ISEV (April 2015, Washington, DC, USA), the International Society on Advancement of Cytometry (June 2015, Glasgow, UK), and the ISTH (June 2015, Toronto, Canada). PMID- 26564380 TI - Late preterm rupture of membranes: it pays to wait. PMID- 26564382 TI - Magnetic order in a novel 3D oxalate-based coordination polymer {[Cu(bpy)3][Mn2(C2O4)3].H2O}n. AB - A heterometallic coordination polymer {[Cu(bpy)3][Mn2(C2O4)3].H2O}n (1; bpy = 2,2'-bipyridine) was synthesized using a building-block approach and characterized by IR spectroscopy, single-crystal X-ray diffraction, magnetization measurement, and X-band ESR spectroscopy both on a single crystal and a polycrystalline sample. The molecular structure of 1 is made of a three dimensional (3D) anionic network [Mn2(C2O4)3]n(2n-) and tris-chelated cations [Cu(bpy)3](2+) occupying the vacancies of the framework. In compound 1 magnetic order is confirmed below 12.8 K - magnetization measurements reveal an antiferromagnetic-like network of canted Mn(2+) spins with incorporated paramagnetic Cu(2+) centres. The ESR spectroscopy distinctly shows the phase transition; above T~ 13 K, single isotropic Lorentzian lines of Mn(2+) ions in the high spin state S = 5/2 were observed, while below this temperature, only characteristic Cu(2+) signals from cations were detected. Thermal decomposition residues of 1 at different temperatures (800-1000 degrees C) were analyzed by powder X-ray diffraction; by heating the sample up to 1000 degrees C the spinel oxide CuMn2O4 [94.1(2) wt%] was formed. From the refined structural parameters, it could be seen that the obtained spinel is characterized by the inversion parameter delta~ 0.8, and therefore the structural formula at room temperature can be written as (tet)[Cu0.17Mn0.83](oct)[Mn1.17Cu0.83]O4. PMID- 26564381 TI - Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. AB - BACKGROUND: Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. METHODS: The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation >=24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. FINDINGS: Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29 (3%) of 912 neonates of mothers assigned to expectant management (relative risk [RR] 0.8, 95% CI 0.5-1.3; p=0.37). The composite secondary outcome of neonatal morbidity and mortality occurred in 73 (8%) of 923 neonates of mothers assigned to immediate delivery and 61 (7%) of 911 neonates of mothers assigned to expectant management (RR 1.2, 95% CI 0.9-1.6; p=0.32). However, neonates born to mothers in the immediate delivery group had increased rates of respiratory distress (76 [8%] of 919 vs 47 [5%] of 910, RR 1.6, 95% CI 1.1-2.30; p=0.008) and any mechanical ventilation (114 [12%] of 923 vs 83 [9%] of 912, RR 1.4, 95% CI 1.0-1.8; p=0.02) and spent more time in intensive care (median 4.0 days [IQR 0.0-10.0] vs 2.0 days [0.0-7.0]; p<0.0001) compared with neonates born to mothers in the expectant management group. Compared with women assigned to the immediate delivery group, those assigned to the expectant management group had higher risks of antepartum or intrapartum haemorrhage (RR 0.6, 95% CI 0.4-0.9), intrapartum fever (0.4, 0.2-0.9), and use of postpartum antibiotics (0.8, 0.7-1.0), and longer hospital stay (p<0.0001), but a lower risk of caesarean delivery (RR 1.4, 95% CI 1.2-1.7). INTERPRETATION: In the absence of overt signs of infection or fetal compromise, a policy of expectant management with appropriate surveillance of maternal and fetal wellbeing should be followed in pregnant women who present with ruptured membranes close to term. FUNDING: Australian National Health and Medical Research Council, the Women's and Children's Hospital Foundation, and The University of Sydney. PMID- 26564383 TI - Pressure-Relief Features of Fixed and Autotitrating Continuous Positive Airway Pressure May Impair Their Efficacy: Evaluation with a Respiratory Bench Model. AB - STUDY OBJECTIVES: Pressure-relief features are aimed at improving the patient's comfort during continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea. The objective of this study was to determine the effect of these therapy features on fixed CPAP and autotitrating CPAP (APAP) treatment efficacy. METHODS: Seven pressure-relief features applied by three CPAP devices were included in our study (Remstar Auto: C-Flex 3, C-Flex+ 3, A-Flex 3, P-Flex; AirSense 10: EPR 3; Prisma 20A: SoftPAP 2 and 3). In fixed CPAP, the devices were subjected to a 10-min bench-simulated obstructive apnea sequence (initial apnea hypopnea index, AHI = 60/h) with and without pressure-relief features. In APAP, the sequence was lengthened to 4.2 h (initial AHI = 58.6/h). The residual AHI and mean/median pressure were compared with and without pressure-relief features. RESULTS: Compared to conventional CPAP, where pressure was adjusted to be just sufficient to control the simulated obstructive events, C-Flex+ 3, P-Flex, and EPR 3 failed to normalize the breathing flow and did not reduce the AHI. The mean pressures with the three features, respectively, were 1.8, 2.6, and 2.6 cmH2O lower than the conventional CPAP. Compared to conventional APAP, similar levels of control were observed with pressure-relief features, apart from P-Flex where the delivered mean pressure was lower and residual AHI greater. The device reported mean/median pressures in APAP with A-Flex 3, P-Flex, EPR 3, and SoftPAP 3 were higher than that measured on the bench. CONCLUSIONS: Pressure-relief features may attenuate CPAP efficacy if not adjusted for at the time of their introduction. In clinical practice, efficacy can be ensured by increasing the therapeutic pressure delivered by fixed CPAP or by enabling the pressure-relief features prior to initial pressure titration. Device-reported pressures in APAP devices with pressure relief activated may overstate delivered pressures. PMID- 26564384 TI - Sleep Disturbances in Traumatic Brain Injury: A Meta-Analysis. AB - STUDY OBJECTIVES: Sleep disturbances are frequently reported following traumatic brain injury (TBI); however, the exact disturbances remain unclear. This meta analysis aimed to characterize sleep disturbance in community dwelling patients with TBI as compared to controls. METHODS: Two investigators independently conducted a systematic search of multiple electronic databases from inception to May 27, 2015. Studies were selected if they compared sleep in community dwelling individuals with TBI relative to a control population without head injury. Data were pooled in meta-analysis with outcomes expressed as the standard mean difference (SMD) and 95% confidence interval (CI). The primary outcomes were derived from polysomnography and secondary outcomes were derived from subjective sleep measures. RESULTS: Sixteen studies were included, combining 637 TBI patients and 567 controls, all of whom were community dwelling. Pooled polysomnography data revealed that TBI patients had poorer sleep efficiency (SMD = -0.47, CI: -0.89, -0.06), shorter total sleep duration (SMD = -0.37, CI: -0.59, -0.16), and greater wake after sleep onset time (SMD = 0.60, CI: 0.33, 0.87). Although sleep architecture was similar between the groups, a trend suggested that TBI patients may spend less time in REM sleep (SMD = -0.22, CI: -0.45, 0.01). Consistent with polysomnographic derangement, TBI patients reported greater subjective sleepiness and poorer perceived sleep quality. CONCLUSIONS: The evidence suggests that TBI is associated with widespread objective and subjective sleep deficits. The present results highlight the need for physicians to monitor and address sleep deficits following TBI. PMID- 26564385 TI - Self-Reporting by Unsafe Drivers Is, with Education, More Effective than Mandatory Reporting by Doctors. AB - STUDY OBJECTIVES: Health professionals are frequently required to report to relevant authorities all drivers who are potentially unsafe due to medical conditions. We aimed to assess both the effect of mandatory reporting (MR) on patient self-predicted behavior and what factors might encourage unsafe drivers to self-report to these authorities. METHODS: We included 5 questions in the South Australian Health Omnibus Survey, an annual, community based, face-to-face survey. We asked (1) how subjects would behave towards their doctor in light of MR if they believed their licences were at risk due to a medical condition; and (2) which factor(s) would cause them to self-report to the same authorities. RESULTS: Responses to 3,007 surveys (response rate 68.5%, age 15-98) showed that 9.0% would avoid diagnosis, lie to their doctor, or doctor shop in order to keep their licence; 30.8% were unaware of the legislated requirement to self-report; and 37.9% were unaware of potentially jeopardizing insurance support if they failed to comply. If educated in these 2 areas, warned about the dangers of driving against medical advice and instructed to do so by their doctor, then 95.8% of people would self-report to the authorities, a number significantly higher than could be reported by their doctors (91.0%). CONCLUSIONS: MR causes 9.0% of people to predict to behave towards their doctor in a manner that reduces road safety. With education and encouragement to do so, more people will self report to the authorities than could be reported by their doctors via the MR pathway. COMMENTARY: A commentary on this article appears in this issue on page 287. PMID- 26564386 TI - Nightmares and Suicide in Posttraumatic Stress Disorder: The Mediating Role of Defeat, Entrapment, and Hopelessness. AB - STUDY OBJECTIVES: Although nightmares appear to be related to suicidal behaviors, the mechanisms which underpin this relationship are unknown. We sought to address this gap by examining a multiple mediation hypothesis whereby nightmares were predicted to have an indirect effect on suicidal behaviors through perceptions of defeat, entrapment, and hopelessness. METHODS: Data were collected from 91 participants who had experienced trauma and symptoms of posttraumatic stress disorder (PTSD). Nightmares were measured by summing the frequency and intensity ratings of relevant items on the Clinician-Administered PTSD Scale. Participants also completed questionnaire measures of suicidal behavior, hopelessness, defeat, and entrapment. Given the interrelations between insomnia, PTSD, and suicide, a measure of insomnia was included as a covariate. Furthermore, analyses were conducted with and without those participants who had comorbid depression. RESULTS: Suicidal behaviors were higher in those participants who experienced nightmares (62%), in comparison to those who did not (20%). Bootstrapped analyses provided support for the hypothesized multistep mediational model. Specifically, nightmares were both directly and indirectly associated with suicidal behaviors, through perceptions of defeat, entrapment, and hopelessness, independent of comorbid insomnia and depression. CONCLUSIONS: For the first time we show that the relationship between nightmares and suicidal behaviors is partially mediated by a multistep pathway via defeat, entrapment, and hopelessness. Clinically, our work highlights the importance of monitoring and targeting nightmares and perceptions of defeat, entrapment, and hopelessness when working with clients who have experienced trauma. COMMENTARY: A commentary on this article appears in this issue on page 289. PMID- 26564387 TI - Cataplexy with Normal Sleep Studies and Normal CSF Hypocretin: An Explanation? AB - Patients with narcolepsy usually develop excessive daytime sleepiness (EDS) before or coincide with the occurrence of cataplexy, with the latter most commonly associated with low cerebrospinal fluid (CSF) hypocretin-1 levels. Cataplexy preceding the development of other features of narcolepsy is a rare phenomenon. We describe a case of isolated cataplexy in the context of two non diagnostic multiple sleep latency tests and normal CSF-hypocretin-1 levels (217 pg/mL) who gradually developed EDS and low CSF-hypocretin-1 (< 110 pg/mL). PMID- 26564389 TI - Noninvasive Ventilation Adherence in Youth with Nocturnal Hypoventilation Secondary to Obesity or Neuromuscular Disorder: It Takes A Village. PMID- 26564388 TI - Individuals with Autism Spectrum Disorders Have Equal Success Rate But Require Longer Periods of Systematic Desensitization than Control Patients to Complete Ambulatory Polysomnography. AB - STUDY OBJECTIVES: Polysomnography (PSG) is the gold standard for the assessment of sleep, yet the extensive apparatus required for monitoring with PSG can be difficult to tolerate, particularly in children. Clinical populations, such as those with anxiety or tactile sensitivity, may have even greater difficulty tolerating the PSG equipment. This study evaluated an innovative protocol for obtaining full PSG in individuals diagnosed autism spectrum disorders (ASD) or developmental delay (DD), as well as typically developing controls (TD). The primary aim was to assess whether this protocol was equally successful for obtaining PSG between these groups. METHODS: One hundred sixty-one individuals were recruited for participation; 93 with a diagnosis of ASD, 23 with a diagnosis of DD, and 45 TD. The participants and families were instructed on a procedure of systematic desensitization to the ambulatory PSG equipment; PSG was performed in the home of the participant. RESULTS: PSG was successfully attained in 144 (89.4%) participants. There was no difference in completion rate by diagnosis (p = 0.1), though younger age (p = 0.018) and duration of desensitization (p = 0.024) did predict PSG failure. Further, it was found that individuals with ASD took longer to desensitize to the equipment (16.08 d), than those with DD (8.04 d) or TD (0.98 d). CONCLUSIONS: Systematic desensitization to PSG equipment, in combination with PSG completed in the home, allows for individuals with ASD to be equally successful in completing PSG, though they do take longer to acclimate to the equipment. PMID- 26564390 TI - [Laron syndrome: Presentation, treatment and prognosis]. AB - Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy. PMID- 26564391 TI - Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring. AB - OBJECTIVE: To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. METHODS: We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. RESULTS: A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. CONCLUSIONS: Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. SIGNIFICANCE: The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. PMID- 26564392 TI - A Simple Mouse Model for the Study of Human Immunodeficiency Virus. AB - Humanized mouse models derived from immune-deficient mice have been the primary tool for studies of human infectious viruses, such as human immunodeficiency virus (HIV). However, the current protocol for constructing humanized mice requires elaborate procedures and complicated techniques, limiting the supply of such mice for viral studies. Here, we report a convenient method for constructing a simple HIV-1 mouse model. Without prior irradiation, NOD/SCID/IL2Rgamma-null (NSG) mice were intraperitoneally injected with 1 * 10(7) adult human peripheral blood mononuclear cells (hu-PBMCs). Four weeks after PBMC inoculation, human CD45(+) cells, and CD3(+)CD4(+) and CD3(+)CD8(+) T cells were detected in peripheral blood, lymph nodes, spleen, and liver, whereas human CD19(+) cells were observed in lymph nodes and spleen. To examine the usefulness of hu-PBMC inoculated NSG (hu-PBMC-NSG) mice as an HIV-1 infection model, we intravenously injected these mice with dual-tropic HIV-1DH12 and X4-tropic HIV-1NL4-3 strains. HIV-1-infected hu-PBMC-NSG mice showed significantly lower human CD4(+) T cell counts and high HIV viral loads in the peripheral blood compared with noninfected hu-PBMC-NSG mice. Following highly active antiretroviral therapy (HAART) and neutralizing antibody treatment, HIV-1 replication was significantly suppressed in HIV-1-infected hu-PBMC-NSG mice without detectable viremia or CD4(+) T cell depletion. Moreover, the numbers of human T cells were maintained in hu-PBMC-NSG mice for at least 10 weeks. Taken together, our results suggest that hu-PBMC-NSG mice may serve as a relevant HIV-1 infection and pathogenesis model that could facilitate in vivo studies of HIV-1 infection and candidate HIV-1 protective drugs. PMID- 26564393 TI - Winter wheat fertilized with biogas residue and mining waste: yielding and the quality of grain. AB - BACKGROUND: Environmental protection problems and efforts to increase agricultural productivity result in attempts to use various organic and mineral wastes as fertilizers. This study aimed to determine the effect of biogas residue (BR) and mining waste (MS) fertilization on wheat yield as well as the nutritional and pro-health quality of grains produced. RESULTS: After the application of MS and BR wheat grain yield was increased compared to unfertilized wheat. The highest grain yield and thousand-grain weight were obtained after MS+BR fertilization. Grains of wheat fertilized with BR and MS+BR contained significantly more protein and wet gluten compared to no fertilization and conventional fertilization (NPK). The studied conditions did not statistically affect starch content. BR fertilization significantly increased the total phenolic content; however, grains of wheat fertilized with NPK were characterized by the highest content of flavonoids and syringic, p-coumaric and sinapic acids. Compared to NPK, waste fertilizations positively affect the reducing power and antiradical activity of wheat. CONCLUSION: These results suggest that the wastes evaluated can be an alternative to conventional fertilization in the soil tested that without any significant deterioration and in some cases significant improvement of yield and wheat quality. (c) 2015 Society of Chemical Industry. PMID- 26564394 TI - How important is the relative balance of fat and carbohydrate as sources of energy in relation to health? AB - Both the intake of fat, especially saturated trans fatty acids, and refined carbohydrates, particularly sugar, have been linked to increased risk of obesity, diabetes and CVD. Dietary guidelines are generally similar throughout the world, restrict both intake of SFA and added sugar to no more than 10 and 35 % energy for total fat and recommend 50 % energy from carbohydrates being derived from unrefined cereals, tubers, fruit and vegetables. Current evidence favours partial replacement of SFA with PUFA with regard to risk of CVD. The translation of these macronutrient targets into food-based dietary guidelines is more complex because some high-fat foods play an important part in meeting nutrient requirements as well as influencing the risk of chronic disease. Some of the recent controversies surrounding the significance of sugar and the type of fat in the diet are discussed. Finally, data from a recently published randomised controlled trial are presented to show the impact of following current dietary guidelines on cardiovascular risk and nutrient intake compared with a traditional UK diet. PMID- 26564395 TI - Developing the Saegusa-Ito Cyclisation for the Synthesis of Difluorinated Cyclohexenones. AB - Palladium(II)-catalysed cycloalkenylation (Saegusa-Ito cyclisation) has been used for the first time to transform difluorinated silylenol ethers to difluorinated cycloalkenones under mild conditions. The silylenol ether precursors were prepared in two high-yielding steps from trifluoroethanol, and cyclised in moderate to good yields. A combination of air and copper(I) chloride in acetonitrile gave the turnover of the initial palladium(II) salt, whereas the provision of an oxygen atmosphere ensured more rapid reaction. Annulations required a minimum level of substitution on the chain, but failed when the alkene was substituted. Annelations allowed a range of n,6-bicyclic systems to be prepared and afforded three products, in which heterocycles were fused to the new cyclohexenone. The least substituted system explored underwent cyclisation followed by terminal oxidation to a cyclic enal, which corresponded to a Wacker product of unusual regiochemistry. PMID- 26564396 TI - Carbon Dioxide Sequestration by Using a Model Carbonic Anhydrase Complex in Tertiary Amine Medium. AB - Globally, the elevation of carbon dioxide (CO2 ) levels due to the anthropogenic effect poses a serious threat to the ecosystem. Hence, it is important to control and/or mitigate the level of CO2 in the atmosphere, which necessitates novel tools. Herein, it is proposed to improve CO2 sequestration by using model complexes based on the enzyme carbonic anhydrase (CA) in aqueous tertiary amine medium. The effect of substituents on the model CA model complexes on CO2 absorption and desorption was determined by using a stopped-flow spectrophotometer to follow pH changes through coupling to pH indicator and a continuous stirred-tank reactor (CSTR). The CO2 hydration rate constants were determined under basic conditions and compound 6, which contained a hydrophilic group, showed the highest absorption or hydration levels of CO2 (2.860*10(3) L mol(-1) s(-1) ). In addition, CSTR results for the absorption and desorption of CO2 suggest that simple model CA complexes could be used in post-combustion processing. PMID- 26564398 TI - Programmed cell death 50 (and beyond). AB - In the 50 years since we described cell death as 'programmed,' we have come far, thanks to the efforts of many brilliant researchers, and we now understand the mechanics, the biochemistry, and the genetics of many of the ways in which cells can die. This knowledge gives us the resources to alter the fates of many cells. However, not all cells respond similarly to the same stimulus, in either sensitivity to the stimulus or timing of the response. Cells prevented from dying through one pathway may survive, survive in a crippled state, or die following a different pathway. To fully capitalize on our knowledge of cell death, we need to understand much more about how cells are targeted to die and what aspects of the history, metabolism, or resources available to individual cells determine how each cell reaches and crosses the threshold at which it commits to death. PMID- 26564399 TI - 9th Tuscany Retreat on Cancer Research: genetic profiling, resistance mechanisms and novel treatment concepts in cancer. PMID- 26564401 TI - Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme. AB - Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2 dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta beta N-acetylglucosaminidase (beta-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards beta hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. PMID- 26564402 TI - Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population-based cohort study. AB - OBJECTIVES: New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS. DESIGN: This observational cohort study linked morbidity, mortality and medication data from Swedish national registries. RESULTS: Overall, 91% (104 012 patients) of all patients admitted to the hospital with an ACS (2009-2013) were alive after discharge and included in this study. Compared with 2009, in 2013 patients investigated with angiography increased by 10%, patients revascularized with percutaneous coronary intervention (PCI) increased by 11% and patients prescribed DAPT increased by 8%. Mean DAPT duration increased from 225 to 298 days in patients investigated with angiography, and from 155 to 208 days in patients who were not investigated with angiography. Furthermore, in patients undergoing angiography a treatment switch from clopidogrel to ticagrelor was observed. DAPT with prasugrel was used to a low extent. Approximately 10% of patients initiated on prasugrel or ticagrelor switched to clopidogrel during the first year of treatment. CONCLUSION: During the study more patients underwent angiography and PCI. There was an increase in the proportion of ACS patients receiving DAPT, as well as longer duration of DAPT in line with ESC guidelines. Among DAPT-treated patients, ticagrelor has emerged as the preferred P2Y12 antagonist in patients undergoing angiography, whereas clopidogrel tended to be prescribed to patients treated non-invasively. PMID- 26564400 TI - An RNA interference screen identifies new avenues for nephroprotection. AB - Acute kidney injury is a major public health problem, which is commonly caused by renal ischemia and is associated with a high risk of mortality and long-term disability. Efforts to develop a treatment for this condition have met with very limited success. We used an RNA interference screen to identify genes (BCL2L14, BLOC1S2, C2ORF42, CPT1A, FBP1, GCNT3, RHOB, SCIN, TACR1, and TNFAIP6) whose suppression improves survival of kidney epithelial cells in in vitro models of oxygen and glucose deprivation. Some of the genes also modulate the toxicity of cisplatin, an anticancer agent whose use is currently limited by nephrotoxicity. Furthermore, pharmacological inhibition of TACR1 product NK1R was protective in a model of mouse renal ischemia, attesting to the in vivo relevance of our findings. These data shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. PMID- 26564403 TI - Truncated seasonal activity patterns of the western blacklegged tick (Ixodes pacificus) in central and southern California. AB - Patterns of seasonal activity and density of host-seeking western blacklegged ticks, Ixodes pacificus, were investigated in central and southern California. Weekly to monthly drag sampling was undertaken at two sites in Santa Barbara County and one site in Los Angeles County over multiple years. Adult I. pacificus became active in the winter (late November) and were rare or absent by late April to early May. Nymphal ticks became active in early to late February, were absent by early May to early June, and were rarely encountered using the drag method throughout their period of peak seasonal activity. Larval ticks became active earlier in the season, or at the same time as nymphs (early to late February) and were absent by early May. These results suggest a highly truncated period of I. pacificus seasonal questing activity, particularly apparent in the juvenile tick stages, in central and southern California relative to observed patterns in Lyme endemic northwestern California. Notably, the highly truncated period of questing activity of the juvenile stages has important implications for pathogen transmission dynamics in that there exists only a brief window for horizontally transmitted pathogens to be acquired by one tick cohort and subsequently transmitted, through hosts, to the next tick cohort in this system. The broader patterns observed also suggest low human risk of tick-borne disease in central and southern California, and have implications for reduced tick-borne disease risk in the western US more generally under projected climate change. PMID- 26564404 TI - The PERS(2) ON score for systemic assessment of symptomatology in palliative care: a pilot study. AB - The comprehensive assessment of symptoms is the basis for effective, individualised palliative treatment. Established scoring systems provide in-depth information but are often lengthy and hence unsuitable. We introduce the PERS(2) ON score as a short and practically feasible score to evaluate symptom burden. Fifty patients admitted to a Palliative Care Unit rated seven items, i.e. pain, eating (loss of appetite/weight loss), rehabilitation (physical impairment), social situation (possibility for home care), suffering (anxiety/burden of disease/depression), O2 (dyspnoea) and nausea/emesis, on a scale ranging from 0 (absence) to 10 (worst imaginable), resulting in a score ranging from 0 to 70. Assessments were performed at admission, 7 days after admission and at the day of discharge. Symptom intensity scores were calculated, and change over time was evaluated. A significant improvement was observed from the PERS2ON score between admission and 7 days (P < 0.001; paired t-test). Significant improvement from baseline evaluation to evaluation on the day of discharge was observed (P = 0.001; paired t-test). This study provides initial evidence that the PERS2ON score is both feasible and sensitive to changes of the most prominent symptoms in palliative care. It may be useful in clinical practice to direct palliative treatment strategies and provide targeted symptom management. PMID- 26564405 TI - Actions of thrombin in the interstitium. AB - Thrombin is a pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis. There is increasing evidence to suggest a role for thrombin in the development of interstitial fibrosis, but interstitial thrombin has not been demonstrated by the direct determination of activity. Rather its presence is inferred by products of thrombin action such as fibrin and activated fibroblasts. This review will focus on possible mechanisms of thrombin formation in the interstitial space, the possible actions of thrombin, processes regulating thrombin activity in the interstitial space, and evidence supporting a role for thrombin in fibrosis. PMID- 26564406 TI - Expression, characterization of a novel nitrilase PpL19 from Pseudomonas psychrotolerans with S-selectivity toward mandelonitrile present in active inclusion bodies. AB - OBJECTIVES: To identify a novel nitrilase with S-selectivity toward mandelonitrile that can produce (S)-mandelic acid in one step. RESULTS: A novel nitrilase PpL19 from Pseudomonas psychrotolerans L19 was discovered by genome mining. It showed S-selectivity with an enantiomeric excess of 52.7 % when used to hydrolyse (R, S)-mandelonitrile. No byproduct was observed. PpL19 was overexpressed in Escherichia coli BL21 (DE3) and formed inclusion bodies that were active toward mandelonitrile and stable across a broad range of temperature and pH. In addition, PpL19 hydrolysed nitriles with diverse structures; arylacetonitriles were the optimal substrates. Homology modelling and docking studies of both enantiomers of mandelonitrile in the active site of nitrilase PpL19 shed light on the enantioselectivity. CONCLUSIONS: A novel nitrilase PpL19 from P. psychrotolerans L19 was mined and distinguished from other nitrilases as it was expressed as an active inclusion body and showed S-selectivity toward mandelonitrile. PMID- 26564407 TI - Synergistic enhancement of bone regeneration by LMP-1 and HIF-1alpha delivered by adipose derived stem cells. AB - OBJECTIVES: To investigate the effect of the combination of LMP-1 and HIF-1alpha delivered by adipose-derived stem cells (ADSCs) on osteogenesis in vitro and in vivo. RESULTS: Cells expressing both LMP-1 and HIF-1alpha genes had elevated mRNA expression of BMP-2, RunX2, alkaline phosphatase, osteocalcin, collagen I and alkaline phosphatase activity compared to cells from other groups. Furthermore, mineralization at day 14 in the cells expressing both LMP-1 and HIF-1alpha was significantly higher than in all the other groups. In vivo, H&E staining and immunohistochemical analysis of the cell-scaffolds also showed more ectopic bone formation at 4 weeks compared to other groups. More new vessel formation was apparent in the pLVX-rHIF-1alpha and pLVX-rLMP-1-rHIF-1alpha groups. CONCLUSION: LMP-1 and HIF-1alpha gene delivery synergistically enhanced the osteo differentiation of ADSCs in vitro and promoted osteogenesis in vivo compared with LMP-1 alone or HIF-1alpha alone. PMID- 26564408 TI - Approaches for recombinant human factor IX production in serum-free suspension cultures. AB - OBJECTIVE: To establish a serum-free suspension process for production of recombinant human factor IX (rhFIX) based on the human cell line HEK 293T by evaluating two approaches: (1) serum-free suspension adaptation of previously genetic modified cells (293T-FIX); and (2) genetic modification of cells already adapted to such conditions (293T/SF-FIX). RESULTS: After 10 months, 293T-FIX cells had become adapted to FreeStyle 293 serum-free medium (SFM) in Erlenmeyer flasks. After 48 and 72 h of culture, 2.1 ug rhFIX/ml and 3.3 ug rhFIX/ml were produced, respectively. However, no biological activity was detected. In the second approach, wild-type 293T cells were adapted to the same SFM (adaptation process took only 2 months) and then genetically modified for rhFIX production. After 48 h of culture, rhFIX reached 1.5 ug/ml with a biological activity of 0.2 IU/ml, while after 72 h, the production was 2.4 ug/ml with a biological activity of 0.3 IU/ml. CONCLUSION: The findings demonstrate that the best approach to establish an rhFIX production process in suspension SFM involves the genetic modification of cells already adapted to the final conditions. This approach is time saving and may better ensure the quality of the produced protein. PMID- 26564409 TI - A cold-adapted and glucose-stimulated type II alpha-glucosidase from a deep-sea bacterium Pseudoalteromonas sp. K8. AB - OBJECTIVES: To express and characterize a putative alpha-glucosidase, Pagl, from Pseudoalteromonas sp. K8 obtained via genome mining approach. RESULTS: Pagl was expressed and purified to homogeneity, with a molecular mass of 60 kDa. It was optimally active at pH 8.5 and 30 degrees C, and showed cold-adapted activity. Pagl exhibited specific activity towards substrates with alpha-1,4-linkage, with the highest specific activity of 19.4 U/mg for maltose, followed by pNPalphaG and maltodextrins, suggesting that Pagl belongs to the type II alpha-glucosidase. Interestingly, the activity of Pagl is significantly enhanced (2.7 times) in the presence of 200 mM glucose. CONCLUSION: The unique catalytic properties of Pagl make it an attractive candidate for several industrial applications. PMID- 26564410 TI - Resolution of P-stereogenic P-heterocycles via the formation of diastereomeric molecular and coordination complexes (a review). AB - TADDOL derivatives and the Ca(2+)-salts of tartaric acid derivatives were found to be versatile and generally applicable resolving agents for the preparation of the enantiomers of P-stereogenic heterocyclic phosphine oxides and phosphinates via the formation of the corresponding diastereomeric molecular and coordination complexes. A few of the diastereomeric intermediates were characterized by single crystal X-ray crystallography to gain insights into the binding mode of the corresponding heterocyclic phosphine oxide ("guest") and the resolving agent ("host") and to study the underlying phenomenon of enantiomeric recognition. PMID- 26564411 TI - Propofol Affects Different Human Brain Regions Depending on Depth of Sedation(?). AB - OBJECTIVE: To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. METHODS: Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. RESULTS: Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. CONCLUSION: Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes. PMID- 26564412 TI - Outcomes of T3a Prostate Cancer with Unfavorable Prognostic Factors Treated with Brachytherapy Combined with External Radiotherapy and Hormone Therapy. AB - OBJECTIVE: To evaluate the outcomes of T3a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy. METHODS: From January 2003 to December 2008, 38 patients classified as T3a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy (brachytherapy + external radiotherapy + hormone therapy). The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy, respectively. The duration of hormone therapy was 2-3 years. The endpoints of this study included biochemical failure-free survival (BFFS), distant metastasis-free survival (DMFS), cancer specific survival (CSS), and overall survival (OS). Survival curves were calculated using the Kaplan-Meier method. The Log-rank test was used to identify the prognostic predictors for univariate analysis. RESULTS: The median follow-up was 71 months. The serum pre-treatment prostate-specific antigen (PSA) level ranged from 10.0 to 99.8 ng/ml (mean 56.3 ng/ml), the Gleason score ranged from 5 to 9 (median 8), and the percentage of positive biopsy cores ranged from 10% to 100% (mean 65%). The 5-year BFFS, DMFS, CSS, and OS rates were 44%, 69%, 82%, and 76%, respectively. All biochemical failures occurred within 40 months. The percentage of positive biopsy cores was significantly correlated with BFFS, DMFS, and OS (all P=0.000), and the Gleason score with DMFS (P=0.000) and OS (P=0.001). CONCLUSIONS: T3a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome. Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival. The percentage of positive biopsy cores and the Gleason score are significant prognostic factors. PMID- 26564413 TI - Accuracy of a Simple Digital Templating in Primary Uncemented Total Hip Arthroplasty. AB - OBJECTIVE: To introduce a simple preoperative digital templating in uncemented total hip arthroplasty (THA) and to determine its accuracy for preoperative size selection of the prostheses. METHODS: A prospective study of digital planned THAs was performed on 90 hips with different types of prostheses from August 2013 to Angust 2014. The plastic templates of different types of prostheses were scanned for desired digital templating and the scanned images were then processed to the transparent, digital templates using Photoshop software. We calibrated the scales of the digital templates with the preoperative radiographs, and then selected the right size of the component. The preoperatively digital planned component sizes were compared to the actual sizes used in the operation, as well as the preoperatively traditional planned sizes. RESULTS: In either cup or stem templating, no difference was found among the groups with different types of prostheses, and the accuracy of digital templating was statistically higher than traditional templating. In cup templating, digital planned and implanted cup sizes were identical in 43.33% of the cases, 78.89% of the cup sizes were predicted within 1 size (+/- 2mm) and 95.56% were predicted within 2 sizes (+/- 4 mm), all significantly higher than the results of traditional planned sizes (30.00%, P=0.044; 61.11%, P=0.007; 82.22%, P=0.004). The exact femoral stem size was predicted in 40.00% of cases using the digital templating, 84.44% of stem sizes were predicted within 1 size, and 93.33% within 2 sizes, better than using traditional templating (25.56%, P=0.028; 53.33%, P<0.001; 77.77%, P=0.003). CONCLUSION: This simple digital preoperative templating is an accurate and reproducible process to preoperatively predict the implant size of uncemented THA. PMID- 26564414 TI - Placement of a Long Intestinal Tube in Patients with Early Postoperative Small Bowel Obstruction under Fluoroscopic Guidance. AB - OBJECTIVE: To investigate the placement of a long tube into the small intestine under fluoroscopic guidance and to evaluate its decompression effect on early postoperative small bowel obstruction (EPSBO). METHODS: Fifty-four patients with EPSBO requiring decompression between April 2010 and July 2014 were enrolled in the study. Insertion of a long tube was guided by fluoroscopy. We first used the guide wire to pass the pylorus and then used the 10 Fr feeding tube as an exchangeable tube to put the superstiff wire into the duodenum. Finally the long tube could be passed over the guide wire through the pylorus into the intestine. The total procedure time, the radiation exposure time, and the incidence of complications were evaluated. RESULTS: The long tubes passed into the jejunum on initial insertion for all patients, so the success rate of this technique was 100%. The long tube was inserted into ileum in 18 patients. The mean total procedure time was 34.4 +/- 8.6 minutes, and the mean radiation exposure time 18.9 +/- 6.8 minutes. A total of 47 patients (87%) experienced full recovery following long-tube decompression and without the need for surgical intervention. CONCLUSIONS: Using the wire-exchange technique, it is easy to place a long tube into the small bowel under fluoroscopic guidance. This decompression method is safe and effective for management of EPSBO. PMID- 26564415 TI - Features of Computed Tomography Perfusion of Mediastinal Lymphadenopathies: a Pathology-based Retrospective Study. AB - OBJECTIVE: To explore the features of various mediastinal lymphadenopathies using computed tomography perfusion (CTP). METHODS: CTP parameters (CTPs) of the selected mediastinal nodes from 59 patients with pathology-proven malignant lymph nodes and of those from 29 patients with clinically diagnosed or pathology-proven inflammatory lymphadenopathies were collected. Patients were divided into subgroups by etiology and phase of primary disease, including different pathological malignant nodes and diverse inflammatory nodes. CTPs were defined as blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and time to peak (TTP). Differences of CTPs were compared between malignant and benign nodes, and among subgroups, respectively. RESULTS: In the mediastinum, no significant differences of CTPs were found between malignant and benign groups (all P>0.05), the same for subgroups of malignant nodes (all P>0.05). Acute lymphadenitis had higher BF and BV than chronic inflammatory, lymphoid tuberculosis, sarcoidosis and malignant nodes. The BF of malignant nodes was markedly slower than that of acute lymphadenitis (P=0.01), but faster than chronic inflammatory nodes (P=0.04) and sarcoidosis (P=0.03), with no significant difference compared with lymphoid tuberculosis. Pneumonia-complicated lymphoid tuberculosis showed the longest MTT while sarcoidosis displayed the shortest MTT, and inflammatory nodes, lymphoid tuberculosis without complicated pneumonia and malignant nodes had moderate MTT. CONCLUSION: CTPs show promising potential in distinguishing various lymphadenopathies in the mediastinum, but more studies are needed to improve their specificity. PMID- 26564416 TI - Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy. AB - OBJECTIVE: To study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease. METHODS: Levels of amyloid protein beta (Abeta42, Abeta40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Abeta42/Abeta40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011. RESULTS: The levels of Abeta42, Abeta40, and P-tau in CSF and ratio of Abeta42/Abeta40 were (660.4 +/- 265.2) ng/L, (7111.0 +/- 1033.4) ng/L, (71.8 +/- 51.5) ng/L, and 0.077 +/- 0.033, respectively in CAA dementia and (663.6 +/- 365.6) ng/L, (5115.0 +/- 2931.1) ng/L, (47.7 +/- 38.8) ng/L, and 0.192 +/- 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05). CONCLUSION: Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease. PMID- 26564417 TI - Double Roots of Mandibular Premolar in Full-mouth Periapical Films. AB - OBJECTIVE: To evaluate the incidence of two-rooted mandibular premolar morphology using full-mouth periapical film series in a Chinese population, with particular emphasis on bilateral incidence, so as to provide a clinical anatomical basis for root canal treatment in mandibular premolars. METHODS: A total of 2015 patients who underwent dental treatment and had full mouth periapical radiographs at the Peking University School of Stomatology from April 2011 to April 2012 were enrolled in this study. Three experienced dentists reviewed the patients' periapical films and classified the root morphology of mandibular premolars bilaterally. The incidence of unilateral and bilateral double roots were recorded and calculated, including confirmed and suspected bucco-lingual root types. RESULTS: In terms of the morphology of two-rooted mandibular first premolars, of the 2015 cases with complete root formation, two-rooted first premolars were detected in 120 cases, with a total number of 159 teeth. According to the number of teeth, the overall incidence of double roots was 4.03% (159/3972). In terms of the morphology of two-rooted mandibular second premolars, of the 2015 cases with complete root formation, two-rooted second premolars were detected in 24 cases, with a total number of 33 teeth. According to the number of teeth, the overall incidence of double roots was 0.85% (33/3880). CONCLUSIONS: The roots of mandibular premolars display specific morphological patterns. Based on a large sample, we observed and calculated not only the occurrence rate of bucco-lingual and mesio-distal double roots in first and second mandibular premolars, but also the incidence of unilateral or bilateral double roots within the same mandible. These findings could provide useful information on the anatomical structure of mandibular premolars for endodontic, prosthodontic and surgical procedures, and could improve the quality of treatment and reduce complications. PMID- 26564418 TI - Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss. AB - In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application. PMID- 26564419 TI - Postpartum Atypical Hemolytic Uremic Syndrome: an Unusual and Severe Complication Associated with IgA Nephropathy. PMID- 26564420 TI - Pulmonary Carcinosarcoma with Intracardiac Extension: a Case Report. PMID- 26564421 TI - Paraneoplastic Dermatomyositis Accompanying Nasopharyngeal Carcinoma. PMID- 26564422 TI - Serum Myeloperoxidase Level in Systemic Lupus Erythematosus. PMID- 26564423 TI - Dysfunction in Motor Coordination in Neonatal White Matter Injury Model Without Apparent Neuron Loss. AB - We made a white matter injury (WMI) model with mild hindlimb dysfunction by right common carotid artery occlusion followed by 6% oxygen for 60 min at postnatal day 3 (P3), in which actively proliferating oligodendrocyte (OL) progenitors are mainly damaged. To know whether this model is appropriate for cell therapy using OL progenitors, the pathological response to mild hypoxia-ischemia (H-I) in neurons and OL lineage cells and myelination failure were investigated along with gene expression analysis. In WMI model rats, coordinated motor function, as assessed by the accelerating rotarod test, was impaired. The dysfunction was accompanied by myelination failure in layers I-IV of the sensorimotor cortex. Although several oligo2-positive OLs stained positive for active caspase 3 in the cortex and white matter at 24 h after H-I, few NeuN-positive neurons were apoptotic. Argyrophil-III staining for damaged neurons revealed no increase in the number of degenerating cells in the model. Moreover, the total number of NeuN positive neurons in the cortex was comparable to that of controls 7 days later. Retrograde labeling of the corticospinal tract with Fluoro-Gold revealed no significant loss of layer V neurons. In addition, no decrease in the numbers of cortical projecting neurons and layers V-VI neurons in both motor and sensory areas was observed. Interestingly, the numbers of inhibitory GABAergic cells immunoreactive for parvalbumin, calretinin, or somatostatin were preserved in the P26 cortex. Gene expression analysis at P5 revealed 98 upregulated and 65 downregulated genes that may relate to cell survival, myelin loss, and differentiation of OLs. These data suggest that impaired motor coordination was not induced by neuron loss but, rather, myelination failure in layers I-IV. As OL lineage cells are mainly damaged, this WMI model might be useful for cell-based therapy by replacing OL progenitors. PMID- 26564425 TI - General Strategy for Enhancing Electrochemiluminescence of Semiconductor Nanocrystals by Hydrogen Peroxide and Potassium Persulfate as Dual Coreactants. AB - Semiconductor nanocrystals usually suffer from weak electrogenerated chemiluminescence (ECL) emissions compared with conventional organic emitters. In this work, we propose, for the first time, a very convenient but effective way to greatly enhance ECL emission of semiconductor TiO2 nanotubes (NTs) by H2O2 and K2S2O8 as dual coreactants, generating ECL emission ca. 6.3 and 107 times stronger than that of K2S2O8 or H2O2 as an individual coreactant, respectively. Scanning electron microscopy, X-ray diffraction, and electron paramagnetic resonance spectral studies were carried out to investigate the ECL enhancement mechanism. The ECL enhancement of TiO2 NTs by the K2S2O8-H2O2 system was supposed to originate from the coordination of H2O2 to the TiO2 surface and the synergy effect between H2O2 and K2S2O8 in the ECL process. The coordination of H2O2 to the surface of TiO2 could stabilize the electrogenerated coreactant-related radical OH(*) (hydroxyl radical), which could obviously promote the amount of sulfate radical anion (SO4(*-)) near the electrode surface by inducing decomposition of K2S2O8 into SO4(*-) or inhibiting the consumption of SO4(*-) by its reaction with H2O. The holes (h(+)) released from SO4(*-) were injected into the valence band of TiO2, resulting in more TiO2(+), which combined with the electrons coming from the conduction band with an enhanced light emission. Moreover, this enhancement effect was also applicable to ECL of a CdS nanocrystal film on a glass carbon electrode, with ca. 2.74- and 148.3-fold enhanced ECL intensity correspondingly, indicating wide applications in the development of semiconductor nanocrystal-based ECL biosensors. PMID- 26564424 TI - Analysis of Dominant HIV Quasispecies Suggests Independent Viral Evolution Within Spinal Granulomas Coinfected with Mycobacterium tuberculosis and HIV-1 Subtype C. AB - Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide, largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified, and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1 clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of putative N-linked glycosylation sites in both compartments. CD68(+) reactivity was associated with higher tissue viral load (r = 1.0; p < 0.01) but not greater intrapatient diversity (r = 0.60; p > 0.05). Ultrastructural imaging revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution. Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the process of viral sequestration within this compartment. PMID- 26564426 TI - Pomegranate peel extract decreases small intestine lipid peroxidation by enhancing activities of major antioxidant enzymes. AB - BACKGROUND: Pomegranate peel extract (PPE) contains several compounds with antioxidative properties. PPE added to foods may interact with endogenous antioxidants and promote health. However, little is known about the biochemical mechanisms by which PPE exerts their actions on tissues of biological systems in vivo. The purpose of this study was to determine the effects of PPE on activities of antioxidant enzymes. Mice were used to investigate the effects of PPE on plasma levels of malondialdehyde (MDA), tissue MDA content and activities of superoxide dismutase 1 (SOD1), SOD2 and glutathione peroxidase (GPX) in the small intestine, liver and skeletal muscle - different tissues involved in the digestion, absorption and metabolism of dietary nutrients. Control mice were fed a standard diet, whereas treated mice were fed for 40 days with the standard diet containing 5% or 10% PPE. RESULTS: Mice fed the 10% PPE diet exhibited lower plasma MDA concentrations, reduced content of MDA in the small intestine and liver and higher levels of SOD1 and GPX activities in the small intestine compared to mice fed the control diet. CONCLUSIONS: These findings demonstrate that intake of PPE in diet attenuates small intestine lipid peroxidation and strengthens the first line of small intestine antioxidant defense by enhancing enzymatic antioxidative pathways. PPE is worthy of further study as a therapeutic approach to prevent peroxidative stress-induced gut pathogenesis. (c) 2015 Society of Chemical Industry. PMID- 26564427 TI - Comparison of Antibiotic Susceptibility Patterns of Bacterial Isolates Based on Time From Hospitalization and Culture Source: Implications for Hospital Antibiograms. AB - We assessed the effects of time from hospitalization and culture source on bacterial susceptibility profiles. Increasing resistance correlated with increasing time from hospitalization for all bacterial groups, with 7 days in hospital representing the best time point for dichotomizing susceptibility rates rather than 48 hours. Antibiograms based on isolates from any source best represented susceptibility profiles. PMID- 26564428 TI - Review: Capripoxvirus Diseases: Current Status and Opportunities for Control. AB - Lumpy skin disease, sheeppox and goatpox are high-impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed. PMID- 26564430 TI - Platelet-rich fibrin: the benefits. AB - Current published data presents confusing results about the effects of platelet rich fibrin on bone, and there is a need for studies that throw light on its effect. Our main objective therefore was to evaluate (by fractal analysis) osseous regeneration in extraction sockets with and without platelet-rich fibrin in a study with a substantial sample and a reliable technique to calibrate its effects on bone cells. We also assessed the soft tissue response. Thirty-four patients had their bilaterally impacted third molars (68 surgical sites) extracted in this split-mouth study, following which platelet-rich fibrin was placed in one of the sockets. Patients were followed up clinically and radiographically, and a pain score and fractal analysis were used to evaluate healing of soft tissue and bone, respectively. We conclude that platelet-rich fibrin improves healing of both soft and hard tissues. Although osseous healing did not differ significantly between the groups, healing of soft tissue as judged by the pain score was significantly better in the experimental group. PMID- 26564429 TI - Synergistic tumor suppression by adenovirus-mediated ING4/PTEN double gene therapy for gastric cancer. AB - Both inhibitor of growth 4 (ING4) and phosphatase and tensin homolog (PTEN) have been shown to be strong candidate tumor suppressors. However, the combined efficacy of ING4 and PTEN for human gastric cancer remains to be determined. In this report, we constructed a multiple promoter expression cassette-based recombinant adenovirus coexpressing ING4 and PTEN (AdVING4/PTEN), assessed the combined effects of AdVING4/PTEN on gastric cancer using wild-type p53 AGS and SNU-1 human gastric cancer cell lines, and elucidated its underlying mechanisms. We found that AdVING4/PTEN-induced synergistic growth inhibition and apoptosis in vitro AGS or SNU-1 tumor cells and in vivo AGS xenografted tumors subcutaneously inoculated in athymic BALB/c nude mice. Mechanistically, AdVING4/PTEN exhibited an enhanced effect on upregulation of p53, Ac-p53 (K382), P21, Bax, PUMA, Noxa, cleaved Caspase-9, cleaved Caspase-3 and cleaved PARP as well as downregulation of Bcl-2 in vitro and in vivo. In addition, AdVING4/PTEN synergistically downregulated tumor vessel CD34 expression and reduced microvessel density, and additively inhibited vascular endothelial growth factor (VEGF) expression in vivo. The synergistic tumor suppression elicited by AdVING4/PTEN was closely associated with the synergistic induction of apoptosis possibly via enhancement of endogenous p53 responses through cooperatively facilitating p53's stability and acetylation, and the synergistic inhibition of tumor angiogenesis probably via overlapping reduction of VEGF through cooperatively downregulating hypoxia inducible factor-1alpha's level and transcription activity. Thus, our results indicate that cancer gene therapy combining ING4 and PTEN may constitute a novel and effective therapeutic modality for human gastric cancer and other cancers. PMID- 26564431 TI - Automated Cross-Sectional Measurement Method of Intracranial Dural Venous Sinuses. AB - BACKGROUND AND PURPOSE: MRV is an important blood vessel imaging and diagnostic tool for the evaluation of stenosis, occlusions, or aneurysms. However, an accurate image-processing tool for vessel comparison is unavailable. The purpose of this study was to develop and test an automated technique for vessel cross sectional analysis. MATERIALS AND METHODS: An algorithm for vessel cross sectional analysis was developed that included 7 main steps: 1) image registration, 2) masking, 3) segmentation, 4) skeletonization, 5) cross-sectional planes, 6) clustering, and 7) cross-sectional analysis. Phantom models were used to validate the technique. The method was also tested on a control subject and a patient with idiopathic intracranial hypertension (4 large sinuses tested: right and left transverse sinuses, superior sagittal sinus, and straight sinus). The cross-sectional area and shape measurements were evaluated before and after lumbar puncture in patients with idiopathic intracranial hypertension. RESULTS: The vessel-analysis algorithm had a high degree of stability with <3% of cross sections manually corrected. All investigated principal cranial blood sinuses had a significant cross-sectional area increase after lumbar puncture (P <= .05). The average triangularity of the transverse sinuses was increased, and the mean circularity of the sinuses was decreased by 6% +/- 12% after lumbar puncture. Comparison of phantom and real data showed that all computed errors were <1 voxel unit, which confirmed that the method provided a very accurate solution. CONCLUSIONS: In this article, we present a novel automated imaging method for cross-sectional vessels analysis. The method can provide an efficient quantitative detection of abnormalities in the dural sinuses. PMID- 26564432 TI - Protrusion of the Infraorbital Nerve into the Maxillary Sinus on CT: Prevalence, Proposed Grading Method, and Suggested Clinical Implications. AB - BACKGROUND AND PURPOSE: The infraorbital nerve arises from the maxillary branch of the trigeminal nerve and normally traverses the orbital floor in the infraorbital canal. Sometimes, however, the infraorbital canal protrudes into the maxillary sinus separate from the orbital floor. We systematically studied the prevalence of this variant. MATERIALS AND METHODS: We performed a retrospective review of 500 consecutive sinus CTs performed at our outpatient centers. The infraorbital nerve protruded into the maxillary sinus if the entire wall of the infraorbital canal was separate from the walls of the sinus. We recorded the length of the bony septum that attached the infraorbital canal to the wall of the maxillary sinus and noted whether the protrusion was bilateral. We also measured the distance from the inferior orbital rim where the infraorbital canal begins to protrude into the sinus. RESULTS: There was a prevalence of 10.8% for infraorbital canal protrusion into the maxillary sinus and 5.6% for bilateral protrusion. The median length of the bony septum attaching the infraorbital canal to a maxillary sinus wall, which was invariably present, was 4 mm. The median distance at which the infraorbital nerve began to protrude into the sinus was 11 mm posterior to the inferior orbital rim. CONCLUSIONS: Although this condition has been reported in only 3 patients previously, infraorbital canal protrusion into the maxillary sinus was present in >10% of our cohort. Identification of this variant on CT could help a surgeon avoid patient injury. PMID- 26564433 TI - Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. AB - An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2 FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1 weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available. PMID- 26564434 TI - Superselective Intra-Arterial Ethanol Sclerotherapy of Feeding Artery and Nidal Aneurysms in Ruptured Cerebral Arteriovenous Malformations. AB - In the endovascular treatment of cerebral arteriovenous malformations, ethanol sclerotherapy is seldom used due to safety concerns. However, when limited reflux of an embolic agent is permissible or when there is a long distance to the target, ethanol may be preferable. We reviewed 10 patients with 14 cerebral AVM feeding artery aneurysms or intranidal aneurysms treated with intra-arterial ethanol sclerotherapy at our institution between 2005 and 2014. All patients presented with acute intracranial hemorrhage. Thirteen of 14 aneurysms were treated primarily with 60%-80% ethanol into the feeding artery. Complete target feeding artery and aneurysm occlusion was seen in all cases; 8/13 (62%) were occluded by using ethanol alone. No retreatments or recurrences were seen. One permanent neurologic deficit (1/13, 7.7%) and no deaths occurred. In a subset of ruptured cerebral AVMs, ethanol sclerotherapy of feeding artery aneurysms and intranidal aneurysms can be performed with a high degree of technical success and a low rate of complication. PMID- 26564435 TI - Acute Preoperative Infarcts and Poor Cerebrovascular Reserve Are Independent Risk Factors for Severe Ischemic Complications following Direct Extracranial Intracranial Bypass for Moyamoya Disease. AB - BACKGROUND AND PURPOSE: Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to MCA bypass in patients with Moyamoya disease. This study was undertaken to determine whether preoperative MR imaging and/or cerebrovascular reserve assessment by using reference standard stable xenon-enhanced CT could predict such complications. MATERIALS AND METHODS: Among all adult patients undergoing direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xenon enhanced CT examination, we identified index cases (patients with >15-mL postoperative infarcts) and control cases (patients without postoperative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated by using the Mann-Whitney U test. Univariate and multivariate generalized linear model regression was used to test predictors of postoperative infarct. RESULTS: Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95 +/- 55 mL. Four of 6 index cases (67%), but no control patients, had preoperative acute infarcts. Baseline CBF was similar, but cerebrovascular reserve was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median cerebrovascular reserve was -0.4% (range, -38.0%-16.6%) in index versus 26.3% (range, -8.2%-60.5%) in control patients (P = .003). Multivariate analysis demonstrated that the presence of a small preoperative infarct (regardless of location) and impaired cerebrovascular reserve were independent, significant predictors of severe postoperative ischemic injury. CONCLUSIONS: Acute infarcts and impaired cerebrovascular reserve on preoperative imaging are independent risk factors for severe ischemic complications following superficial temporal artery to MCA bypass in Moyamoya disease. PMID- 26564436 TI - Disorders of Microtubule Function in Neurons: Imaging Correlates. AB - BACKGROUND AND PURPOSE: A number of recent studies have described malformations of cortical development with mutations of components of microtubules and microtubule-associated proteins. Despite examinations of a large number of MRIs, good phenotype-genotype correlations have been elusive. Additionally, most of these studies focused exclusively on cerebral cortical findings. The purpose of this study was to characterize imaging findings associated with disorders of microtubule function. MATERIALS AND METHODS: MRIs from 18 patients with confirmed tubulin mutations (8 TUBA1A, 5 TUBB2B, and 5 TUBB3) and 15 patients with known mutations of the genes encoding microtubule-associated proteins (5 LIS1, 4 DCX, and 6 DYNC1H1) were carefully visually analyzed and compared. Specific note was made of the cortical gyral pattern, basal ganglia, and white matter to assess internal capsular size, cortical thickness, ventricular and cisternal size, and the size and contours of the brain stem, cerebellar hemispheres and vermis, and the corpus callosum of patients with tubulin and microtubule-associated protein gene mutations. Results were determined by unanimous consensus of the authors. RESULTS: All patients had abnormal findings on MR imaging. A large number of patients with tubulin gene mutations were found to have multiple cortical and subcortical abnormalities, including microcephaly, ventriculomegaly, abnormal gyral and sulcal patterns (termed "dysgyria"), a small or absent corpus callosum, and a small pons. All patients with microtubule-associated protein mutations also had abnormal cerebral cortices (predominantly pachygyria and agyria), but fewer subcortical abnormalities were noted. CONCLUSIONS: Comparison of MRIs from patients with known mutations of tubulin genes and microtubule-associated proteins allows the establishment of some early correlations of phenotype with genotype and may assist in identification and diagnosis of these rare disorders. PMID- 26564437 TI - Giant Intracranial Aneurysms at 7T MRI. AB - Giant intracranial aneurysms are rare vascular pathologies associated with high morbidity and mortality. The purpose of this in vivo study was to assess giant intracranial aneurysms and their wall microstructure by 7T MR imaging, previously only visualized in histopathologic examinations. Seven giant intracranial aneurysms were evaluated, and 2 aneurysms were available for histopathologic examination. Six of 7 (85.7%) showed intraluminal thrombus of various sizes. Aneurysm walls were depicted as hypointense in TOF-MRA and SWI sequences with excellent contrast ratios to adjacent brain parenchyma (range, 0.01-0.60 and 0.58 0.96, respectively). The triple-layered microstructure of the aneurysm walls was visualized in all aneurysms in TOF-MRA and SWI. This could be related to iron deposition in the wall, similar to the findings in 2 available histopathologic specimens. In vivo 7T TOF-MRA and SWI can delineate the aneurysm wall and the triple-layered wall microstructure in giant intracranial aneurysms. PMID- 26564438 TI - Contrast Leakage Patterns from Dynamic Susceptibility Contrast Perfusion MRI in the Grading of Primary Pediatric Brain Tumors. AB - BACKGROUND AND PURPOSE: The pattern of contrast leakage from DSC tissue signal intensity time curves have shown utility in distinguishing adult brain neoplasms, but has limited description in the literature for pediatric brain tumors. The purpose of this study is to evaluate the utility of grading pediatric brain tumors with this technique. MATERIALS AND METHODS: A retrospective review of tissue signal-intensity time curves from 63 pediatric brain tumors with preoperative DSC perfusion MR imaging was performed independently by 2 neuroradiologists. Tissue signal-intensity time curves were generated from ROIs placed in the highest perceived tumor relative CBV. The postbolus portion of the curve was independently classified as returning to baseline, continuing above baseline (T1-dominant contrast leakage), or failing to return to baseline (T2* dominant contrast leakage). Interobserver agreement of curve classification was evaluated by using the Cohen kappa. A consensus classification of curve type was obtained in discrepant cases, and the consensus classification was compared with tumor histology and World Health Organization grade. RESULTS: Tissue signal intensity time curve classification concordance was 0.69 (95% CI, 0.54-0.84) overall and 0.79 (95% CI, 0.59-0.91) for a T1-dominant contrast leakage pattern. Twenty-five of 25 tumors with consensus T1-dominant contrast leakage were low grade (positive predictive value, 1.0; 95% CI, 0.83-1.00). By comparison, tumors with consensus T2*-dominant contrast leakage or return to baseline were predominantly high-grade (10/15 and 15/23, respectively) with a high negative predictive value (1.0; 95% CI, 0.83-1.0). For pilomyxoid or pilocytic astrocytomas, a T1-dominant leak demonstrated high sensitivity (0.91; 95% CI, 0.70-0.98) and specificity (0.90, 95% CI, 0.75-0.97). CONCLUSIONS: There was good interobserver agreement in the classification of DSC perfusion tissue signal intensity time curves for pediatric brain tumors, particularly for T1-dominant leakage. Among patients with pediatric brain tumors, a T1-dominant leakage pattern is highly specific for a low-grade tumor and demonstrates high sensitivity and specificity for pilocytic or pilomyxoid astrocytomas. PMID- 26564439 TI - Increased Facet Fluid Predicts Dynamic Changes in the Dural Sac Size on Axial Loaded MRI in Patients with Lumbar Spinal Canal Stenosis. AB - BACKGROUND AND PURPOSE: Axial-loaded MR imaging, which simulates the spinal canal in a standing position, demonstrates reductions of the dural sac cross-sectional area in patients with lumbar spinal canal stenosis. However, there has been no useful conventional MR imaging finding for predicting a reduction in the dural sac cross-sectional area on axial-loaded MR imaging. Previous studies have shown that increased facet fluid is associated with the spinal instability detected during positional changes. The purpose of this study was to analyze the correlations between facet fluid and dynamic changes in the dural sac cross sectional area on axial-loaded MR imaging. MATERIALS AND METHODS: In 93 patients with lumbar spinal canal stenosis, the dural sac cross-sectional area was measured by using axial images of conventional and axial-loaded MR imaging. Changes in the dural sac cross-sectional area induced by axial loading were calculated. The correlation between the facet fluid width measured on conventional MR imaging and the change in dural sac cross-sectional area was analyzed. The change in the dural sac cross-sectional area was compared between the intervertebral levels with and without the facet fluid width that was over the cutoff value determined in this study. RESULTS: The dural sac cross-sectional area was significantly smaller on axial-loaded MR imaging than on conventional MR imaging. The facet fluid width significantly correlated with the change in the dural sac cross-sectional area (r = 0.73, P < .001). The change in the dural sac cross-sectional area at the intervertebral level with the facet fluid width over the cutoff value was significantly greater than that at the other level. CONCLUSIONS: The increased facet fluid on conventional MR imaging is highly predictive of the dynamic reduction of dural sac cross-sectional area detected on axial-loaded MR imaging in the clinical assessment of lumbar spinal canal stenosis. PMID- 26564440 TI - Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging. AB - BACKGROUND AND PURPOSE: Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. MATERIALS AND METHODS: Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. RESULTS: Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. CONCLUSIONS: The effects of normal aging on brain metabolites and microstructure are region dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. PMID- 26564441 TI - Utility and Significance of Gadolinium-Based Contrast Enhancement in Posterior Reversible Encephalopathy Syndrome. AB - BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is a clinicoradiologic syndrome. Literature regarding associated factors and the prognostic significance of contrast enhancement in posterior reversible encephalopathy syndrome is sparse. This study set out to evaluate an association between the presence of enhancement in posterior reversible encephalopathy syndrome and various clinical factors in a large series of patients with this syndrome. MATERIALS AND METHODS: From an MR imaging report search that yielded 176 patients with clinically confirmed posterior reversible encephalopathy syndrome between 1997 and 2014, we identified 135 patients who had received gadolinium-based contrast. The presenting symptoms, etiology, clinical follow-up, and maximum systolic and diastolic blood pressures within 1 day of MR imaging were recorded. MRIs were reviewed for parenchymal hemorrhage, MR imaging severity, and the presence and pattern of contrast enhancement. Statistical analyses evaluated a correlation between any clinical features and the presence or pattern of enhancement. RESULTS: Of 135 included patients (67.4% females; age range, 7-82 years), 59 (43.7%) had contrast enhancement on T1-weighted MR imaging, the most common pattern being leptomeningeal (n = 24, 17.8%) or leptomeningeal plus cortical (n = 21, 15.6%). Clinical outcomes were available in 96 patients. No significant association was found between the presence or pattern of enhancement and any of the variables, including sex, age, symptom, MR imaging severity, blood pressure, or outcome (all P > .05 after Bonferroni correction). CONCLUSIONS: The presence or pattern of enhancement in posterior reversible encephalopathy syndrome is not associated with any of the tested variables. However, an association was found between MR imaging severity and clinical outcome. PMID- 26564442 TI - Mechanical Thrombectomy for Isolated M2 Occlusions: A Post Hoc Analysis of the STAR, SWIFT, and SWIFT PRIME Studies. AB - BACKGROUND AND PURPOSE: Mechanical thrombectomy is beneficial for patients with acute ischemic stroke and a proximal anterior occlusion, but it is unclear if these results can be extrapolated to patients with an M2 occlusion. The purpose of this study was to examine the technical aspects, safety, and outcomes of mechanical thrombectomy with a stent retriever in patients with an isolated M2 occlusion who were included in 3 large multicenter prospective studies. MATERIALS AND METHODS: We included patients from the Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), Solitaire With the Intention For Thrombectomy (SWIFT), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) studies, 3 large multicenter prospective studies on thrombectomy for ischemic stroke. We compared outcomes and technical details of patients with an M2 with those with an M1 occlusion. All patients were treated with a stent retriever. Imaging data and outcomes were scored by an independent core laboratory. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b/3. RESULTS: We included 50 patients with an M2 and 249 patients with an M1 occlusion. Patients with an M2 occlusion were older (mean age, 71 versus 67 years; P = .04) and had a lower NIHSS score (median, 13 versus 17; P < .001) compared with those with an M1 occlusion. Procedural time was nonsignificantly shorter in patients with an M2 occlusion (median, 29 versus 35 minutes; P = .41). The average number of passes with a stent retriever was also nonsignificantly lower in patients with an M2 occlusion (mean, 1.4 versus 1.7; P = .07). There were no significant differences in successful reperfusion (85% versus 82%, P = .82), symptomatic intracerebral hemorrhages (2% versus 2%, P = 1.0), device-related serious adverse events (6% versus 4%, P = .46), or modified Rankin Scale score 0-2 at follow-up (60% versus 56%, P = .64). CONCLUSIONS: Endovascular reperfusion therapy appears to be feasible in selected patients with ischemic stroke and an M2 occlusion. PMID- 26564443 TI - Validity of the Meyer Scale for Assessment of Coiled Aneurysms and Aneurysm Recurrence. AB - BACKGROUND AND PURPOSE: Both the Meyer and Raymond scales are commonly used to report angiographic outcomes following coil embolization of intracranial aneurysms. The objectives of this study were the following: 1) to assess the interobserver agreement of the Meyer and Raymond scales, and 2) to evaluate and compare their performance in predicting major recurrence at follow-up. MATERIALS AND METHODS: A retrospective series of 120 coiled aneurysms was included. Four investigators independently graded DSA images immediately posttreatment and at follow-up according to the Meyer and Raymond scales. On follow-up DSA, readers also evaluated recurrence outcome. Interobserver agreement was assessed via the intraclass correlation coefficient. The ability of posttreatment Meyer and Raymond scales to predict major recurrence was modeled by using logistic regression and assessed by using receiver operating characteristic analysis. RESULTS: For the Meyer scale, interobserver intraclass correlation coefficients were 0.58 (95% CI, 0.46-0.68) on posttreatment and 0.78 (95% CI, 0.72-0.83) on follow-up evaluations. For the Raymond scale, interobserver intraclass correlation coefficients were 0.50 (95% CI, 0.39-0.61) and 0.69 (95% CI, 0.62 0.76), respectively, for posttreatment and follow-up. The areas under the curve for the receiver operating characteristic analyses regarding the performance to predict major recurrence at follow-up were 0.69 (95% CI, 0.60-0.79) for the Meyer and 0.70 (95% CI, 0.61-0.78) for the Raymond scale. CONCLUSIONS: The Meyer scale appears consistent and reliable with observer agreement as high or higher than that of the Raymond scale. Performance of both scales in predicting the risk of major recurrence at follow-up is adequate, with no statistical difference between the scales. PMID- 26564444 TI - In Utero MR Imaging of Fetal Holoprosencephaly: A Structured Approach to Diagnosis and Classification. AB - BACKGROUND AND PURPOSE: Holoprosencephaly is a rare developmental brain abnormality with a range of severity. We describe our experience in diagnosing holoprosencephaly in the fetus with in utero MR imaging. We hypothesized that including in utero MR imaging in the diagnostic pathway will improve the detection of holoprosencephaly compared with ultrasonography and allow better assessment of the severity. MATERIALS AND METHODS: We report on holoprosencephaly identified from ultrasonography and/or a diagnosis of holoprosencephaly made with in utero MR imaging. We compare the diagnoses made with sonography and in utero MR imaging in each case and compare the 2 methods of assessing the severity of holoprosencephaly. RESULTS: Thirty-five fetuses are reported, including 9 in which the diagnosis of holoprosencephaly was made on ultrasonography but not confirmed on in utero MR imaging. Of the 26 cases of holoprosencephaly diagnosed on in utero MR imaging, 12 were not recognized on ultrasonography. CONCLUSIONS: Our results show that in utero MR imaging has a major role in diagnosing or refuting a diagnosis of fetal holoprosencephaly made on ultrasonography. In utero MR imaging also assists in grading the severity of fetal holoprosencephaly. PMID- 26564445 TI - Georges Salamon. PMID- 26564447 TI - Individual support plans of people with intellectual disabilities in residential services: content analysis of goals and resources in relation to client characteristics. AB - BACKGROUND: Goals and objectives as mentioned in Individual Support Plans (ISPs) were analysed to explore what domains of quality of life they are associated with, what support resources are referenced for achieving the goals, and how domains and resources are related to clients age, gender and intellectual disability (ID) level. METHOD: A total of 209 ISPs for persons with ID from eight residential Dutch service provider organisations were analysed. Mixed linear regression analyses were conducted to examine the relations between client characteristics and the content of goals and support resources. RESULTS: Results showed that ISPs of people with mild and moderate ID had significantly more goals related to independence and social participation as compared to the ISPs of people with severe and profound ID. ISPs of clients with profound ID addressed quality of life factors related to 'well-being' more than ISPs of all other clients. ISPs of people aged 20-34 years had significantly more goals on independence than the two other age groups. ISPs of people under the age of 50 had significantly fewer goals with respect to well-being than found in ISPs of older people. Regarding the use of resources, 42.6% of the ISP goals were associated with resources from specialised services, 31.5% associated with natural resources and 25.9% associated with a combination of both natural and specialised services. In ISPs of people with mild ID, natural resources are more often mentioned, and specialised service-based resources are less often mentioned than for other people. CONCLUSIONS: This study offers empirical feedback on ISP practices in the field of ID in the Netherlands. In light of current ISP practices, results suggest that attention should be paid to: (1) distinguishing between a 'service contract' and an ISP; (2) keeping a focus on the whole person in all age groups and levels of functioning and (3) involving the service recipient in ISP development and implementation. PMID- 26564446 TI - Longitudinal changes in corneal curvature and its relationship to axial length in the Correction of Myopia Evaluation Trial (COMET) cohort. AB - PURPOSE: To describe longitudinal changes in corneal curvature (CC) and axial length (AL) over 14 years, and to explore the relationship between AL and CC, and the axial length/corneal radius (AL/CR) ratio. METHODS: In total 469, 6 to <12 year-old, children were enrolled in COMET. Measurements of refractive error, CC (D), CR (mm), and ocular component dimensions including AL were gathered annually. Linear mixed models were used to evaluate longitudinal changes adjusting for covariates (gender, ethnicity, lens type, baseline age and baseline refraction). The Pearson correlation coefficient between AL and CC was computed at each visit. RESULTS: There was a slight but significant (p<0.0001) flattening in CC over 14 years. At all visits females had significantly steeper CC than males (overall difference=0.53 D, p<0.0001). Caucasians had the steepest CC, and Hispanics the flattest (p=0.001). The correlation between AL and CC was -0.70 (p<0.0001) at baseline (mean age=9.3 years) and decreased to -0.53 (p<0.0001) at the 14-year visit (mean age=24.1 years). The average AL/CR ratio was 3.15 at baseline and increased to 3.31 at the 14-year visit. The correlation between the magnitude of myopia and AL/CR ratio was significantly higher (p<0.0001) at each visit than the correlation between myopia and AL alone. CONCLUSIONS: Differences in average corneal curvature by age, gender, and ethnicity observed in early childhood remain consistent as myopia progresses and stabilizes. This study also demonstrates increases in the AL/CR ratio as myopia progresses and then stabilizes, supporting observations from previous cross-sectional data. PMID- 26564448 TI - Development of a microfluidic device for cell concentration and blood cell-plasma separation. AB - This work presents design, fabrication and test of a microfluidic device which employs Fahraeus-Lindqvist and Zweifach-Fung effects for cell concentration and blood cell-plasma separation. The device design comprises a straight main channel with a series of branched channels placed symmetrically on both sides of the main channel. The design implements constrictions before each junction (branching point) in order to direct cells that would have migrated closer to the wall (naturally or after liquid extraction at a junction) towards the centre of the main channel. Theoretical and numerical analysis are performed for design of the microchannel network to ensure that a minimum flow rate ratio (of 2.5:1, main channel-to-side channels) is maintained at each junction and predict flow rate at the plasma outlet. The dimensions and location of the constrictions were determined using numerical simulations. The effect of presence of constrictions before the junctions was demonstrated by comparing the performances of the device with and without constrictions. To demonstrate the performance of the device, initial experiments were performed with polystyrene microbeads (10 and 15 MUm size) and droplets. Finally, the device was used for concentration of HL60 cells and separation of plasma and cells in diluted blood samples. The cell concentration and blood-plasma purification efficiency was quantified using Haemocytometer and Fluorescence-Activated Cell Sorter (FACS). A seven-fold cell concentration was obtained with HL60 cells and a purification efficiency of 70 % and plasma recovery of 80 % was observed for diluted (1:20) blood sample. FACS was used to identify cell lysis and the cell viability was checked using Trypan Blue test which showed that more than 99 % cells are alive indicating the suitability of the device for practical use. The proposed device has potential to be used as a sample preparation module in lab on chip based diagnostic platforms. PMID- 26564449 TI - Coronary Artery Dominance as a Prognostic Factor: In Anterior Myocardial Infarctions as Well? PMID- 26564450 TI - [Comparison of Clinical Influence of Intramedullary versus Extramedullary Alignment Guides on Total Knee Arthroplasty]. AB - Objective: To compare the clinical influence of intramedullary versus extramedullary alignment guides on total knee arthroplasty (TKA) in terms of alignment of the lower limbs,intraoperative tourniquet time,and postoperative complications. METHODS: We retrospectively analyzed the clinical data of 105 patients(210 knees)undergoing bilateral TKA from February 2012 to November 2013. All patients were divided to two groups:40 [age:(66.65 +/- 9.57)years] were implanted using intramedullary guides on the tibia and 65 [age:(65.29+/ 9.27)years] were implanted using extramedullary guides on the tibia. Alignment of lower limb,tibial component angle in the sagittal plane,tourniquet time,and postoperative complications were compared. RESULTS: The gender ratio,age,height,weight,body mass index,and preoperative alignment of lower limbs were not significantly different between these two groups (all P>0.05). The average coronal alignment of lower extremity was (179.69 +/- 2.91) degrees in the intramedullary guides group and (178.26 +/- 3.38) degrees in the extramedullary guides group (P=0.002). The alignment of lower limbs on neutral and valgus position were found in 68 cases(85.00%)in the intramedullary group and in 94 cases (72.31%) in extramedullary group (P=0.033) ;the tourniquet time was (79.46 +/- 12.06) min in the intramedullary group and (84.68 +/- 8.02) min in the extramedullary group (P=0.001); the postoperative complication rate was 6.25% in intramedullary group and 3.07% in extramedullary group (P=0.279). CONCLUSION: Alignment and tourniquet time can be significantly improved by the intramedullary instrumentation,while the incidence of complications associated with intramedullary instrumentation is higher than extramedullary instrumentation. PMID- 26564451 TI - [Imaging Findings of Ovarian Fibrothecoma]. AB - OBJECTIVE: To summarize the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian fibro the coma and to compare them with the pathological findings. METHOD: CT and MRI features of 25 patients with pathologically proved ovarian fibrothecoma were retrospectively analyzed. RESULTS: Of these 25 patients,the tumors were single in 23 patients and bilateral in 2 patients. The tumors were round or oval in 16 cases and lobulated in 11 cases. CT plate scanning showed that both the solid masses and the solid components of the cystic and solid masses had slightly lower densities than that of the myometrium, and gradual and mild enhancement could be found in the arterial phase and delay phase after enhanced scan. MRI showed iso-low signal on T1-weighted imaging, slightly low or high signal on T2-weighted imaging of fat suppression sequences, slightly high signal on diffusion weighted imaging and the enhance characteristics as the well as CT after enhanced scan.Pelvic cavity effusion was seen in 3 cases. CONCLUSION: Ovarian fibrothecoma have certain imaging characteristics,which are helpful to improve the diagnosis and differential diagnosis of this disease and lower the misdiagnosis rate before operation. PMID- 26564452 TI - [Effect of Individualized Low-protein Diet Intervention on Renal Function of Patients with Chronic Kidney Disease]. AB - OBJECTIVE: To investigate whether individualized low-protein diet intervention for patients with chronic kidney disease(CKD)could improve the general condition,slow the deterioration of renal function,and delay the time of entering dialysis. METHODS: Forty CKD inpatients between July 2011 and July 2012 were randomly given with normal or individualized low-protein diet for six months according to random number table after signing informed consent. The levels of urine protein and biochemical indexes of renal function were measured at baseline and at the end of dietary intervention for six months, respectively. RESULTS: The baseline urine protein level,renal function,and biochemical indexes were not significantly different between these two groups. The diastolic blood pressure,protein intake,blood urea nitrogen,uric acid, potassium, phosphorus, C reaction protein,24-hour urea nitrogen,and urine protein after six months were significantly lower than those at baseline,that is,(101.70 +/- 15.78)mmHg vs.(91.75 +/-15.52) mmHg,(63.87 +/- 24.70)g/d vs.(50.02 +/- 14.07)g/d,(20.01 +/- 7.69)mmol/L vs.(15.11 +/- 4.90) mmol/L,(362.75 +/- 84.56)MUmol/L vs.(302.20 +/- 8.48)MUmol/L,(5.22 +/- 0.75)mmol/L vs.(4.79+/-0.36) mmol/L,(2.07 +/- 0.68) mmol/L vs.(1.57 +/- 0.41) mmol/L,1.19 [0.65,4.17] mg/L vs. 0.74 [0.38,1.33] mg/L,70.6 [8.70,101.18] mmol/L vs. 16.93 [3.23,72.27] mmol/L,1.00 [0.30,1.00] g/d vs. 0.15 [0,0.83] g/d (all P<0.05),among which albumin and hemoglobin were significantly higher [(0.34 +/- 0.07)g/L vs.(0.37 +/- 0.05)g/L, (99.38 +/- 21.89)g/L vs.(126.35 +/- 14.11)g/L,respectively] in the individualized low-protein diet group. The difference was statistically significant (P<0.05). The most relevant for urine protein producing was prealbumin (r=0.924, P<0.05). The differences of blood urea nitrogen, potassium, sodium, calcium, phosphorus, 24-hour urea nitrogen, urine specific gravity, urine protein, and hemoglobin in six months in the individualized low-protein diet group were significantly better than those in the normal low protein-diet group (P<0.05). CONCLUSIONS: Individualized low-protein diet intervention may have definite curative effectiveness in CKD patients. It can markedly improve the patients' condition,slow down the deterio-ration of renal function,and increase serum prealbumin levels that may reduce the generation of urine protein. It is worthy of wider clinical application. PMID- 26564453 TI - [Localized Scleroderma of Lower Extremities:Clinical and Magnetic Resonance Imaging Features]. AB - OBJECTIVE: To evaluate the clinical and musculoskeletal characteristics of localized scleroderma with lower extremities affected. METHODS: All the localized scleroderma patients,who received magnetic resonance (MR ) examinations of affected lower extremities at Peking Union Medical College Hospital from April 2013 to June 2014,were retrospectively reviewed. Their clinical data and laboratory results of antinuclear antibody,anti-double stranded-DNA antibody, and anti-extractable nuclear antigen antibody were collected and analyzed. All the MR examinations were non-contrast imaging using Siemens Skyra 3.0T MR scanner. RESULTS: There were 16 localized scleroderma patients with lower extremities affected, 11 of whom were linear scleroderma, 4 generalized morphea, and 1 deep morphea. Female to male ratio was 1:2.2. The mean age was 22.5 years. The mean time span was 7.4 years. Four of the 14 patients (28.6%) who received antinuclear antibody test were positive. All the 10 patients who received anti-double stranded-DNA antibody test and the 7 patients who received anti-extractable nuclear antigen antibody test were negative. The most common musculoskeletal MR features were subcutaneous septal thickening (16/16) and fascial thickening (11/16). The thickened speta and fascia could either be hypointenstiy or hyperintensity on turbo inversion recovery magnitude/proton density weighted imaging. Other MR manifestations were intramuscular speta thickening (3/16), muscular abnormal signals (1/16), and bone marrow abnormal signals (2/16). CONCLUSION: Musculoskeletal manifestations of the lower extremities with localized scleroderma can be well revealed using MR imaging. PMID- 26564454 TI - [Low-dose Tertiary Prophylactic Therapy for Severe Haemophilia A Adults in A Single Medical Center in Beijing Area]. AB - OBJECTIVE: To investigate the benefit of low-dose tertiary prophylaxis in adults with severe haemophilia A(SHA). METHODS: Twenty-two SHA patients aged 18 to 60 years from the Haemophilia Centre of Peking Union Medical College Hospital, Beijing, China, were retrospectively observed from their one year on-demand treatment to one year tertiary prophylaxis using plasma derived factor 8 concentrates at 5-10 IU/kg 2-3x per week. All the patients had already developed arthropathy. Gilbert and the functional independence scores in hemophilia were used to assess the joint status and the ability in the activities of daily living of the patients. RESULTS: Comparing with on-demand therapy,the annual bleeding frequency during low-dose tertiary prophylaxis decreased significantly by 72.7%,from 39.9 +/- 21.5 to 11.1 +/- 7.2 (P<0.0001),the total Gilbert score decreased from 50.5+/-32.1 to 45.2+/-29.6(P<0.05),and the total functional independence score in hemophilia score increased from 18.6 +/- 5.2 to 21.7 +/- 4.1 (P<0.05). CONCLUSION Low-dose tertiary prophylaxis in adults with SHA is beneficial by reducing bleeding frequency, improving the health status of joints, and improving the activities of daily living, thus raising the quality of life. PMID- 26564455 TI - [Surgical Diagnosis and Treatment of Primary Hyperthyroidism Complicated with Occult Thyroid Carcinoma]. AB - OBJECTIVE: To evaluate the surgical diagnosis and treatment of primary hyperthyroidism complicated with occult thyroid carcinoma. METHOD: Data of 51 cases of primary hyperthyroidism complicated with occult thyroid carcinoma admitted during January 2004 to November 2014 were analyzed retrospectively. RESULTS: The incidence of occult thyroid carcinoma was 5.03% in hyperthyroidism,and 47 cases (92.16%) were female. The preoperative diagnosis of all these 51 cases was primary hyperthyroidism and 11 cases were diagnosed thyroid carcinoma at the same time;25 cases were diagnosed thyroid carcinoma by frozen section and the remaining 26 cases were diagnosed by postoperative pathology. Finally,26 cases underwent subtotal thyroidectomy,4 cases underwent total thyroidectomy, and 21 cases underwent total thyroidectomy with lymphadenectomy. The tumor size ranged from 0.1 to 1.0 cm [mean:(0.63 +/- 0.35) cm]. The lesions were less than or equal to 0.5 cm in 28 cases (54.9%). The follow-up lasted from 1 to 121 months [mean:(28.6 +/- 22.7)months] in 43 patients,and all of them survived. CONCLUSIONS: Primary hyperthyroidism complicated with occult thyroid carcinoma is commonly found in female patients. Preoperative diagnosis is difficult. Ultrasound is the major examining method. Frozen section can increase the detection rate. The postoperative prognosis of hyperthyroidism complicated with occult thyroid carcinoma is satisfactory. PMID- 26564456 TI - [Roles of Tumor-infiltrating Lymphocytes in Non-small Cell Lung Cancer Recurrence and Metastasis:A Meta Analysis]. AB - OBJECTIVE: To determine the prognostic value of tumor-infiltrating lymphocytes in the recurrence and metastasis of non-small cell lung cancer (NSCLC). METHODS: A PubMed, EMBASE, Cochrane Library databases, NIH databases, and China Biology Medicine disc, China National Knowledge Infrastructure, Chinese Science and Technology Periodical literature search strategy was designed. Studies on the prognostic values of intratumoural CD3+,CD4+,CD8+, and FoxP3+lymphocytes for NSLCL were retrieved. RevMan 5.1 was applied for Meta analysis. RESULTS: Totally 8 studies entered the final analysis. In pooled analysis of 1197 patients,the high expressions of CD3+ and CD8+ cells were correlated with the increase of overall survival (OS) (OR=0.52,95% CI=0.40- 0.68, P<0.0001; OR=0.52,95% CI=0.34 0.79,P=0.002), and the high expression of CD8+ was significantly correlated with the increase of disease-free survival (DFS) (OR=0.68,95% CI=0.51-0.91,P=0.01). The CD4+ cell expression level was not significantly correlated with OS or DFS (P=0.14, P=0.73). The high expression of FoxP3+ cells did not favor the DFS(OR=1.78,95% CI=1.36-2.31; P<0.0001). CONCLUSION: The expression levels of CD3+, CD8+ and FoxP3+ in NSCLC microenviroment are related with the prognosis of NSCLC, while the role of CD4+ in the development of NSCLC warrants further investigations. PMID- 26564457 TI - [Effectiveness of Meibomian Gland Tube Massage in Treating Meibomian Gland Dysfunction]. AB - OBJECTIVE: To observe the clinical effectiveness of meibomian gland tube massage in treating meibomian gland dysfunction (MGD). METHODS: All patients were divided into medicine group (tropically administered with corticosteroid eye ointment and artificial tears)and massage group (meibomian gland tube massage in addition to these drugs) using random numbers. At different period(before treatment and after treatment 2,4 weeks), the slip-lamp microscopy and intraocular pressure measurement were performed. Ocular symptoms were evaluated by questionnaire of ocular surface disease index (OSDI), and corneal fluorescein staining scores (CFS) was used for checking the epithelial integrity,tear film breakup time (TBUT), and tear secretion (Schirmer I test,SIt). RESULTS: Before the treatment, the OSDI score,TBUT, CFS, and SIt showed no statistical significance between these two groups (all P>0.05). After the treatment, the symptoms, damage of corneal epithelium, quality of tear film,tear secretion were significantly improved in both groups(P<0.05), and were significantly superior in the massage group than in the medicine group (all P<0.01; but CFS t4w=6.60,P>0.05). CONCLUSION: The meibomian gland tube massage in combination with drug therapy can improve the treatment effectives for MGD. PMID- 26564458 TI - [Endoscopic Saphenous Vein Harvesting versus Open Vein Harvesting Techniques]. AB - OBJECTIVE: To investigate whether endoscopic saphenous vein harvesting (EVH )reduces leg wound morbidity and improves rehabilitation of lower extremity as compared to open vein harvesting (OVH) in patients with coronary artery disease. METHODS: The clinical data of 333 patients who underwent isolated coronary artery bypass graft surgery (CABG) between January 2007 and December 2011 were retrospectively analyzed.These patients were divided into EVH group (n=210) and OVH group (n=123). Parameters including age,sex,with/without diabetes mellitus,leg wound complications rate,postoperative hospital stay,hospitalization expense,and vein graft patency were analyzed. RESULTS: The age,sex,with/without diabetes mellitus were not significantly different between two groups (P>0.05). However,the incidences of leg wound complications, poor wound healing, wound infections, wound pain,wound numbness, and edema of lower extremity were significantly lower in the EVH group than the OVH group (P<0.05). The ecchymoma and deep vein thrombosis incidences were not significantly different between these two groups (P>0.05). The postoperative hospital stay showed no significant difference (P>0.05), while the hospitalization expense was significantly higher in the EVH group than in the OVH group (P<0.05). There was no statistical difference of vein graft patency (P>0.05). CONCLUSION: The EVH system is a safe and effective alternative to OVH because it can markedly reduce postoperative leg wound morbidity and the EVH vein graft has good patency. PMID- 26564459 TI - [Ultrasonographic Features of Pseudomyxoma Peritonei and TheirComparison with Computed Tomographic Findings]. AB - OBJECTIVE: To investigate the value of ultrasound in the diagnosis of pseudomyxoma peritonei (PMP) and summarize the ultrasonographic features of PMP by comparing with computed tomography (CT) findings. METHOD: Ultrasound and CT scan results of 25 patients with PMP confirmed by pathology after surgery were analyzed retrospectively. RESULTS: Among these 25 PMP patients,three were diagnosed by ultrasound and six by CT(P=0.579). The specific ultrasonographic features of PMP were as follows:the dense punctuate echoes or floccules were detected in hydrops abdominis,which seldom or never move with the change of body position. Honeycomb-like lesions were typical. Notches were formed on the surface of liver or spleen due to the mucinous material and/or the mucinous lesions. CONCLUSIONS: Both ultrasound and CT scan have poor detection rate in the diagnosis of PMP. PMP has specific ultrasonographic features,which may make it possible to diagnose most PMP lesions by ultrasound before surgery PMID- 26564460 TI - [Evaluation of Off-label Use of Oral Glucocorticoids in Outpatients]. AB - OBJECTIVE: To investigate the off-label use of oral glucocorticoids in outpatients. METHODS: The information of outpatient glucocorticoids prescriptions from January 1st to June 30th in 2012 were collected from the information system in our hospital, then the software of Excel was employed to statistically analyze the data including the amount of drugs used in different departments,as well as the age, sex, and diagnosis of the patients. The diagnoses were compared with those included in the labels approved by China Food and Drug Administration and US Food and Drug Administration and domestic and foreign guidelines. RESULTS: It was found that 16.53% of the cases were off-label use,and dexamethasone had the highest proportion (60.50%) of off-label use. Most of the off-label use had evidence support, such as multiple myeloma and myasthenia gravis, while some cases did not, such as epilepsy and sudden deafness. CONCLUSION: The management of off-label use should be further strengthened to promote the safe and rational use of glucocorticoids. PMID- 26564461 TI - [Effect of Modified Baizhu Powder on Gastrointestinal Functions in Mouse Models with Stomach-cold Functional Dyspepsia]. AB - OBJECTIVE: To explore the effect of modified Baizhu (Rhizoma Atractylodis Macrocephalae) powder on the gastrointestinal function in mouse models with stomach-cold functional dyspepsia. Meanwhile,the mouse models were administered with Shihu (dendrobium), a traditional Chinese drug with cold nature and flavour, to explore the way via which it exert its effect on specific symptoms. Methods: Mouse models with stomach-cold functional dyspepsia were established by ice water and ice NaOH. The effects of modified Baizhu powder and dendrobium on mice were observed in terms of water intake, weight change,small intestine propulsion rate, intestinal absorption function, and effects on ghrelin and motilin. RESULTS: The modified Baizhu powder effectively increased food intake, water intake, body weight (P<0.05) and swimming time (P<0.01), increased the small intestine propulsion rate and serum D-xylose content (P<0.05), and up-regulated ghrelin (P<0.05). Also, it showed a trend to down-regulate the motilin, although the change was not statistically significant (P>0.05). In contrast,the use of Shihu aggravated symptoms in the mouse models. Conclusion: The changes in ghrelin and motilin levels may be the neuro-endocrine mechanisms via which the modified Baizhu powder and Shihu exert their effects on mouse models. PMID- 26564462 TI - [Effect of Intestinal Ischemia-reperfusion Injury on the Expression of Chemerin in Mice]. AB - OBJECTIVE: To investigate the effect of intestinal ischemia-reperfusion on the protein expression of chemerin in C57BL/6J mice. METHODS: A total of 16 mice (C57BL/6J, specific pathogen free level) were randomly assigned into two groups (n=8 each): the intestinal ischemia-reperfusion group and the sham group. The intestinal ischemia-reperfusion state was achieved by blocking the super mesenteric artery. After 60 minutes of ischemia followed by 60 minutes of reperfusion,we determined the protein level of chemerin in various organs and tissues by enzyme-linked immunosorbent assay and Western blot. The sham group underwent the same operation process except for the blocking of the super mesenteric artery. RESULT: The protein level of chemerin was significantly elevated in distinctive organs and tissues in the state of intestinal ischemia reperfusion (P<0.05). CONCLUSION: The intestinal ischemia-reperfusion can remarkably increase the protein expression of chemerin in some organs and tissues. PMID- 26564463 TI - [Morphology of Hypertrophic Scar Tissues and Expressions of Vascular Endothelial Growth Factor and Transforming Growth Factor Beta Activated Kinase 1 in These Tissues]. AB - OBJECTIVE: To observe the morphology of hypertrophic scar tissue and explore the expressions and distribution of vascular endothelial growth factor (VEGF) and transforming growth factor beta activated kinase 1(TAK1 )in these tissues. METHOD: Hematoxylin-eosin staining, Masson staining,immunofluorescence,and real time polymerase chain reaction were used to detect the localization and expression of VEGF and TAK1 in 15 hypertrophic scar tissues and 10 normal skin tissues. RESULTS: Morphological observation showed that the dermal fibroblasts in hypertrophic scar were disorderly and densely arranged (compared to the normal skin). Immunofluorescence displayed that the expressions of VEGF and TAK1 in hypertrophic scar tissue were higher than in normal skin tissues. Real-time polymerase chain reaction showed the mRNA expressions of both VEGF and TAK1 were significantly higher in hypertrophic scar tissue than in normal tissue (P<0.01, P<0.05,respectively). CONCLUSIONS: Hypertrophic scar tissue has higher collagen fibrosis degree and higher TAK1 and VEGF expressions than the normal skin. VEGF and TAK1 can be used as the reference indicators for the diagnosis and differential diagnosis of hypertrophic scar and serve as new therapeutic targets. PMID- 26564464 TI - [Alisma versus Gliclazide in the Treatment of Primary Diabetes in Goto-Kakizaki Rats]. AB - OBJECTIVE: To compare the roles of alisma and gliclazide in the treatment of diabetes in Goto-Kakizaki (GK) rats. METHODS: GK rats were randomly divided into alisma group, gliclazide group, and blank group, and Wistar rats were used as the normal group. After two weeks of treatment, body weight, food intake,fasting glucose, impaired glucose tolerance, and other indicators were measured. RESULTS: The body weight increased after the treatment in the normal group,blank group,and gliclazide group [(241.3 +/- 7.0)g vs.(263.5 +/- 11.1)g, (242.8 +/- 7.1)g vs.(267.9 +/- 16.8)g, (243.9 +/- 12.2)g vs.(277.9 +/- 9.8)g, P<0.05] but decreased in alisma group [(244.6 +/- 9.2)g vs.(227.9 +/- 13.7)g, P<0.05]. The food intake showed no significant change before and after administration among different groups(P>0.05). Fasting glucose was significantly lower in normal group than in control group,alisma group,and gliclazide group [(4.8 +/- 0.2) mmol/L vs.(8.2 +/- 1.4) mmol/L,(8.1 +/- 0.6) mmol/L, (8.1 +/- 0.9)mmol/L, P<0.05] one week after drug administration; it was not significantly different among blank group,alisma group,and gliclazide group before drug administration (P>0.05); however, it significantly decreased in alisma group and gliclazide group two weeks after administration [(6.9 +/- 0.7) mmol/L vs.(8.1 +/- 0.6) mmol/L; (5.8 +/ 0.5) mmol/L vs.(8.1 +/- 0.9) mmol/L, P<0.05]; compared with the blank group, the fasting glucose was significantly lower in the alisma group and gliclazide group,and it was also significantly different between these two groups [(6.9 +/- 0.7) mmol/L vs.(8.8 +/- 0.6) mmol/L,(5.8 +/- 0.5)mmol/L vs.(8.8 +/- 0.6)mmol/L, (6.9 +/- 0.7) mmol/L vs.(5.8 +/- 0.5)mmol/L, P<0.05]. Compared with the normal group,glucose tolerance was abnormal in blank group,alisma group,and gliclazide group;after two weeks of treatment,glucose tolerance was significantly improved in alisma group (P<0.05); compared with the pretreatment level and that in the blank group,the glucose tolerance in gliclazide group showed no significant difference (P> 0.05). CONCLUSIONS: Both alisma and gliclazide monotherapy is effective in lowering fasting blood glucose. As a single-target drug,gliclazide has stronger effecacy in lowering fasting glucose. However, alisma, as a mixture, can also control weight and improve glucose intolerance. PMID- 26564465 TI - [Effect of Basic Fibroblast Growth Factor and Transforming Growth Factor-Beta1 Combined with Bone Marrow Mesenchymal Stem Cells on the Repair of Degenerated Intervertebral Discs in Rat Models]. AB - OBJECTIVE: To evaluate the effects of the combination of basic fibroblast growth factor (bFGF), transforming growth factor-Beta1 (TGF-Beta1), bone marrow mesenchymal stem cells (BMSCs), and temperature-responsive chitosan hydrogel (TCH) gel on the repair of degenerative intervertebral disc in rat models. METHODS: Rat models of intervertebral disc degeneration were established by acupuncture. The degenerative effects were observed under magnetic resonance imaging (MRI). The BMSCs was cultured in vitro and then transfected by adenovirus with enhanced green fluorescent protein to make it carry the gene of enhanced green fluorescent protein,which functioned as fluorescence labeling. The SD rat models of intervertebral disc degeneration were divided into four groups: group A, treated with the combination of bFGF, TGF-Beta1,BMSCs,and TCH gel; group B, treated with the combination of BMSCs and TCH gel;group C, treated with the combination of bFGF,TGF-Beta1, and TCH gel;and group D, treated with PBS buffer solution. After the corresponding reagents were injected into the degenerative intervertebral discs of each group, the rats were cultivated for another four weeks and then the repair effects of the intervertebral discs were observed under MRI. Furthermore,the intervertebral discs of each group were taken out and observed by HE and Masson staining. The nucleus pulposus was aspirated and the expressions of aggrecan,collagen 2,Sox-9,and collagen I of nucleus pulposus of each group were tested by reverse transcription polymerase chain reaction and Western blot. RESULTS: The transplanted BMSCs survived in the intervertebral disc and differentiated into nucleus pulposus-like cells. MRI showed that:the signal intensity of the nucleus pulposus of group A was much higher than that of the rest groups, the signal intensity of group B was higher than that of group C, and the signal intensity of group D was the lowest,in which the dura mater spinalis was in compression and the spinal cord changed in beaded shape. The differences of the Pfirrmann grading among the four groups had statistical significance (P<0.05). The results of the HE and Masson stains showed:the intervertebral disc of group A was well-structured,the quantity of nucleus pulposus cells was larger than that of the other three groups,and the boundary between the nucleus pulposus and the annulus fibrosus was clearly defined;the quantity of the nucleus pulposus cells of group B was larger than that of group C, and the broken annulus fibrosus was not observed in group B, while the broken annulus fibrosus could be observed in group C; and, the nucleus pulposus cells of group D were replaced by fibrous tissue. The results of the reverse transcription polymerase chain reaction and Western blot tests showed that,in terms of the expressions of aggrecan,collagen 2 and Sox-9,group A was the highest, followed by group B,group C,and group D (P<0.05); in terms of the expression of collagen 1,there was no obvious difference among these four groups (P>0.05). CONCLUSIONS: The transplanted BMSCs can survive in the degenerative intervertebral disc and differentiate into nucleus pulposus-like cells. The combination of bFGF, TGF-Beta1, BMSCs,and TCH gel has obvious repair effect on the degenerative intervertebral discs. The effect of the combination of BMSCs and TCH gel on transplantation therapy of the degenerative intervertebral discs is better than that of the combination of bFGF, TGF-Beta1 and TCH gel but worse than that of the combination of bFGF, TGF-Beta1, BMSCs, and TCH gel. PMID- 26564466 TI - [Diagnosis and Treatment of Pituitary Carcinoma]. AB - The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options. PMID- 26564467 TI - [Perioperative Challenges and Strategies for Patent Foramen Ovale Patients Undergoing Non-cardiac Surgery]. AB - The close relationship between patent foramen ovale(PFO)and cryptogenic ischemic cerebrovascular disease and migraine has been concerned for years. However,in the field of non-cardiac surgery and anesthesiology, PFO and related clinical problems are less recognized. Under perioperative circumstances,PFO may generate many challenges such as paradoxical systematic embolism and severe hypoxemia. This article briefly introduces the epidemiology, paradoxical embolism, and detection methods of PFO and discribes the perioperative complications and corresponding perioperative strategies for prevention and cure. PMID- 26564468 TI - [Advances in Genomics Studies for Coronary Artery Disease]. AB - Coronary artery disease (CAD) is one of the major life-threatening diseases. In addition to traditional risk factors including age, sex, smoking, hypertension,and diabetes, genomic studies have shown that CAD has obvious genetic predisposition. In recent years, the rapid advances in genomics shed new light on early diagnosis, risk stratification and new treatment targets. PMID- 26564469 TI - [Advances in the Association between Apolipoprotein (a) Gene Polymorphisms and Coronary Heart Disease]. AB - Human apolipoprotein (a) (LPA) gene is highly polymorphic, and the polymorphic loci on this gene include the Kringle 4 subtype 2(KIV-2) repeat polymorphism, the pentanucleotide repeat (TTTTA)n polymorphism, and a number of single nucleotide polymorphisms. KIV-2 repeat polymorphism was found to be significantly associated with coronary heart disease(CHD), and the reducing number of KIV-2 repeats is a risk factor for CHD. Both the increase and decrease of the pentanucleotide repeat(TTTTA)n polymorphism repeats are possibly associated with CHD risk. In single nucleotide polymorphisms loci, the rs10455872 and rs3798220 loci were widely reported to be associated with CHD, while other loci were less reported. The association between LPA polymorphisms and CHD may be mediated by either the elevation of plasma LPA level or the change of LPA subtypes. This article reviews the association between the LPA polymorphisms and CHD and the underlying mechanisms. PMID- 26564471 TI - Versatile structures of group 13 metal halide complexes with 4,4'-bipy: from 1D coordination polymers to 2D and 3D metal-organic frameworks. AB - A systematic structural study of complexes formed by aluminium and gallium trihalides with 4,4'-bipyridine (bipy) in 2 : 1, 1 : 1, and 1 : 2 stoichiometric ratios has been performed. Molecular structures of 11 complexes in the solid state have been determined for the first time. Complexes of 2 : 1 composition are molecular, while complexes of 1 : 1 composition form metal-organic frameworks of different kinds: an ionic 3D network (three interpenetrated lvt nets for AlCl3bipy), an ionic 2D network for AlBr3bipy and GaBr3bipy and a 1D coordination polymer in the case of GaCl3bipy. Thus, the nature of the Lewis acid plays a critical role in the structural type of the complex in the solid state. Incorporation of excess bipy molecules into (GaCl3bipy)infinity (formation of crystallosolvate) leads to an unprecedented change of the molecular structure from a non-ionic 1D coordination polymer to an ionic 2D metal organic framework [GaCl2bipy2](+)[GaCl4](-).2bipy. As indicated by the temperature-dependent XRD study, removal of bipy by heating in a vacuum restores the non-ionic 1D structure. Quantum chemical computations for simple cluster model systems (up to eight Al and Ga atoms) reveal that ionic forms are slightly favourable, although the energy differences between the ionic and non-ionic structures are not large. These theoretical predictions are in good agreement with experimental findings. Thus, even relatively simple cluster models may be used to indicate the structural preferences in the solid state. Both experimental and computational IR frequency shifts of the in-plane ring bending mode of bipy upon complexation correlate well with the M-N bond distances in the complexes. PMID- 26564472 TI - Doxorubicin-Loaded Carborane-Conjugated Polymeric Nanoparticles as Delivery System for Combination Cancer Therapy. AB - Carborane-conjugated amphiphilic copolymer nanoparticles were designed to deliver anticancer drugs for the combination of chemotherapy and boron neutron capture therapy (BNCT). Poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2(2-dicarba closo-dodecarborane)propyloxycarbonyl-propyne carbonate) (PLMB) was synthesized via the versatile reaction between decaborane and side alkynyl groups, and self assembled with doxorubicin (DOX) to form drug-loaded nanoparticles. These DOX@PLMB nanoparticles could not only suppress the leakage of the boron compounds into the bloodstream due to the covalent bonds between carborane and polymer main chains, but also protect DOX from initial burst release at physiological conditions because of the dihydrogen bonds between DOX and carborane. It was demonstrated that DOX@PLMB nanoparticles could selectively deliver boron atoms and DOX to the tumor site simultaneously in vivo. Under the combination of chemotherapy and BNCT, the highest tumor suppression efficiency without reduction of body weight was achieved. This polymeric nanoparticles delivery system could be very useful in future chemoradiotherapy to obtain improved therapeutic effect with reduced systemic toxicity. PMID- 26564470 TI - Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease. AB - AIMS: Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (alpha-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity. RESULTS: We first demonstrate excessive free radical production in a human induced pluripotent stem-derived alpha-S triplication model at basal levels and on application of picomolar doses of beta-sheet-rich alpha-S oligomers. We probed the effects of different structural species of alpha-S in wild-type rat neuronal cultures and show that both oligomeric and fibrillar forms of alpha-S are capable of generating free radical production, but that only the oligomeric form results in reduction of endogenous glutathione and subsequent neuronal toxicity. We dissected the mechanism of oligomer-induced free radical production and found that it was interestingly independent of several known cellular enzymatic sources. INNOVATION: The oligomer-induced reactive oxygen species (ROS) production was entirely dependent on the presence of free metal ions as addition of metal chelators was able to block oligomer-induced ROS production and prevent oligomer-induced neuronal death. CONCLUSION: Our findings further support the causative role of soluble amyloid oligomers in triggering neurodegeneration and shed light into the mechanisms by which these species cause neuronal damage, which, we show here, can be amenable to modulation through the use of metal chelation. PMID- 26564473 TI - Protective immunity in gibel carp, Carassius gibelio of the truncated proteins of cyprinid herpesvirus 2 expressed in Pichia pastoris. AB - Cyprinid herpesvirus 2 (CyHV-2) infection is a newly emerged infectious disease of farmed gibel carp (Carassius gibelio) in China and causes huge economic losses to the aquaculture industry. In this study, the three membrane proteins encoded by genes ORF25, ORF25C, and ORF25D of CyHV-2 were truncated and expressed in yeast, Pichia pastoris. Screening of the recombinant yeasts was done by detecting the truncated proteins using Western blot. Through immunogold labeling, it was shown that proteins binding the colloidal gold were presented on the surface of cells. In the experiment of inhibition of virus binding by the recombinant truncated proteins, the TCID50 of the tORF25 group (10(4.1)/ml) was lower than that of tORF25C (10(4.6)/ml) or tORF25D groups (10(5)/ml). These results suggested that the proteins may be involved in attachment of the virus to the cell surface. Healthy gibel carp were immunized with 20 MUg of tORF25, tORF25C, and tORF25D proteins, and the control group received PBS. Interleukin 11 (IL-11) expression in the spleens of the immunized fish peaked at day 4 and the complement component C3 (C3) genes were significantly up-regulated at day 7 post immunization. Specific antibodies were measured in the three immunized groups and the titer detected in the tORF25 group reached 327, that was significantly higher than the tORF25C (247) or tORF25D (228) groups. When the immunized fish were challenged with live CyHV-2 by intraperitoneal injection the relative percent survival (RPS) of the tORF25, tORF25C, and tORF25D immunized groups was 75%, 63%, and 54%, respectively. The feasibility of the P. pastoris yeast expression system for the production of the recombinant truncated proteins and their apparent bioactivity suggests that tORF25, tORF25C, and tORF25D are potential candidate vaccines against Cyprinid herpesvirus 2 infection in gibel carp. PMID- 26564474 TI - Dietary beta-glucan (MacroGard(r)) enhances survival of first feeding turbot (Scophthalmus maximus) larvae by altering immunity, metabolism and microbiota. AB - Reflecting the natural biology of mass spawning fish aquaculture production of fish larvae is often hampered by high and unpredictable mortality rates. The present study aimed to enhance larval performance and immunity via the oral administration of an immunomodulator, beta-glucan (MacroGard((r))) in turbot (Scophthalmus maximus). Rotifers (Brachionus plicatilis) were incubated with or without yeast beta-1,3/1,6-glucan in form of MacroGard((r)) at a concentration of 0.5 g/L. Rotifers were fed to first feeding turbot larvae once a day. From day 13 dph onwards all tanks were additionally fed untreated Artemia sp. nauplii (1 nauplius ml/L). Daily mortality was monitored and larvae were sampled at 11 and 24 dph for expression of 30 genes, microbiota analysis, trypsin activity and size measurements. Along with the feeding of beta-glucan daily mortality was significantly reduced by ca. 15% and an alteration of the larval microbiota was observed. At 11 dph gene expression of trypsin and chymotrypsin was elevated in the MacroGard((r)) fed fish, which resulted in heightened tryptic enzyme activity. No effect on genes encoding antioxidative proteins was observed, whilst the immune response was clearly modulated by beta-glucan. At 11 dph complement component c3 was elevated whilst cytokines, antimicrobial peptides, toll like receptor 3 and heat shock protein 70 were not affected. At the later time point (24 dph) an anti-inflammatory effect in form of a down-regulation of hsp 70, tnf alpha and il-1beta was observed. We conclude that the administration of MacroGard((r)) induced an immunomodulatory response and could be used as an effective measure to increase survival in rearing of turbot. PMID- 26564475 TI - The effects of Mg enrichment of vegetable sprouts on Mg concentration, yield and ROS generation. AB - BACKGROUND: Two-thirds of the world's population do not consume the recommended amount of Mg, hence the demand for the production of Mg-enriched plants. Sprouts represent promising targets for enrichment. This study evaluated the effects of enriching broccoli, radish, alfalfa and mung bean sprouts with Mg (50-300 mg L( 1) ) on (i) the concentration of Mg and other ions, (ii) biomass accumulation, (iii) levels of reactive oxygen species (ROS), and (iv) the activity/content of enzymatic and non-enzymatic components of antioxidative systems. RESULTS: Enrichment of sprouts with Mg led to a significant increase in Mg concentration, especially in alfalfa (increase of 23-152 %), without depletion of other ions. A higher Mg concentration had a minor effect on biomass accumulation, but increased, often significantly, ROS generation and affected enzymatic and non enzymatic antioxidative systems. The level of O2 (*-) increased most in broccoli, by 59-158%, while OH(*) increased most in radish, by 200-350%. CONCLUSIONS: Enrichment of sprouts with Mg is possible, but attention must be paid to elevated ROS levels in food. Mung bean sprouts are best suited to enrichment as they make a considerable contribution to the daily supplementation of Mg, at still low levels of ROS in enriched plants. (c) 2015 Society of Chemical Industry. PMID- 26564476 TI - A phosphorylation code of the Aspergillus nidulans global regulator VelvetA (VeA) determines specific functions. AB - The velvet protein VeA is a global fungal regulator for morphogenetic pathways as well as for the control of secondary metabolism. It is found exclusively in filamentous fungi, where it fulfills conserved, but also unique functions in different species. The involvement of VeA in various morphogenetic and metabolic pathways is probably due to spatially and timely controlled specific protein protein interactions with other regulators such as phytochrome (FphA) or velvet like proteins (VelB). Here we present evidence that Aspergillus nidulans VeA is a multi-phosphorylated protein and hypothesize that at least four specific amino acids (T167, T170, S183 and Y254) undergo reversible phosphorylation to trigger development and sterigmatocystin biosynthesis. Double mutation of T167 to valine and T170 to glutamic acid exerted the largest effects with regards to sexual development and veA gene expression. In comparison with wild-type VeA, which shuttles out of the nuclei after illumination this VeA variant showed stronger nuclear accumulation than the wild type, independent of the light conditions. The interaction between VeA and VelB or FphA, respectively, was affected in the T167V T170E mutant. Our results suggest complex regulation of the phosphorylation status of the VeA protein. PMID- 26564477 TI - Catalytic C-F bond activation of geminal difluorocyclopropanes by nickel(I) complexes via a radical mechanism. AB - Nickel(II) fluorido complexes bearing NNN-pincer ligands were found to be catalysts in the hydrodefluorination of geminal difluorocyclopropanes which undergo ring-opening to form the corresponding monofluoroalkenes in good yield and high Z-selectivities. Evidence for a radical based mechanism involving nickel(I) and nickel hydrido complexes as key intermediates was obtained in the corresponding stoichiometric reactions. PMID- 26564478 TI - Preconception-related needs of reproductive-aged women. AB - OBJECTIVE: to assess women's interest in preconception care, their organisational preferences, and their preconception-related information and support needs. DESIGN: cross-sectional study design. SETTING: participants were recruited online through social media and discussion forums for issues relating to (in)fertility, pregnancy and parenting, and at the Women's Clinic of Ghent University Hospital. PARTICIPANTS: 242 reproductive-aged women with a desire to have (more) children. FINDINGS: the majority of women (75%) wanted to receive preconception care in the future. Gynaecologists (93%) were the preferred source of preconception care, followed by midwives (73%) and general practitioners (63%). Most women wanted information about lifestyle, environmental exposures, working conditions and medical issues. Information needs were higher among women with (history of) mental illness [odds ratio (OR) 3.50, 95% confidence interval (CI) 1.08-11.36], (history of) eye and otolaryngological problems (OR 2.22, 95% CI 0.95-5.21) and overweight (OR 2.22, 95% CI 1.01-4.93). A few women indicated that they needed preconception-related support. Overweight women reported greater need for lifestyle-related support compared with women of healthy weight (p=0.001). KEY CONCLUSIONS: reproductive-aged women are interested in preconception care, and would prefer to receive this care directly from a professional caregiver. Most women had high preconception-related information needs and lower support needs. IMPLICATIONS FOR PRACTICE: although women reported that they would prefer to receive preconception care from gynaecologists, the results indicate that midwives can also play an important role in the provision of preconception care. They would need further training to improve their knowledge, skills and awareness regarding preconception care. PMID- 26564479 TI - Estimating the burden of acute gastrointestinal illness due to Giardia, Cryptosporidium, Campylobacter, E. coli O157 and norovirus associated with private wells and small water systems in Canada. AB - Waterborne illness related to the consumption of contaminated or inadequately treated water is a global public health concern. Although the magnitude of drinking water-related illnesses in developed countries is lower than that observed in developing regions of the world, drinking water is still responsible for a proportion of all cases of acute gastrointestinal illness (AGI) in Canada. The estimated burden of endemic AGI in Canada is 20.5 million cases annually - this estimate accounts for under-reporting and under-diagnosis. About 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. There is evidence that individuals served by private systems and small community systems may be more at risk of waterborne illness than those served by municipal drinking water systems in Canada. However, little is known regarding the contribution of these systems to the overall drinking water-related AGI burden in Canada. Private water supplies serve an estimated 12% of the Canadian population, or ~4.1 million people. An estimated 1.4 million (4.1%) people in Canada are served by small groundwater (2.6%) and surface water (1.5%) supplies. The objective of this research is to estimate the number of AGI cases attributable to water consumption from these supplies in Canada using a quantitative microbial risk assessment (QMRA) approach. This provides a framework for others to develop burden of waterborne illness estimates for small water supplies. A multi-pathogen QMRA of Giardia, Cryptosporidium, Campylobacter, E. coli O157 and norovirus, chosen as index waterborne pathogens, for various source water and treatment combinations was performed. It is estimated that 103 230 AGI cases per year are due to the presence of these five pathogens in drinking water from private and small community water systems in Canada. In addition to providing a mechanism to assess the potential burden of AGI attributed to small systems and private well water in Canada, this research supports the use of QMRA as an effective source attribution tool when there is a lack of randomized controlled trial data to evaluate the public health risk of an exposure source. QMRA is also a powerful tool for identifying existing knowledge gaps on the national scale to inform future surveillance and research efforts. PMID- 26564480 TI - Mutation analysis of PALB2 gene in French breast cancer families. AB - Several population-based and family-based studies have demonstrated that germline mutations of the PALB2 gene (Partner and Localizer of BRCA2) are associated with an increased risk of breast cancer. Distinct mutation frequencies and spectrums have been described depending on the population studied. Here we describe the first complete PALB2 coding sequence screening in the French population. We screened the complete coding sequence and intron-exon boundaries of PALB2, using the EMMA technique, to assess the contribution of pathogenic mutations in a set of 835 familial breast cancer cases and 662 unrelated controls from the French national study GENESIS and the Paul Strauss Cancer Centre, all previously tested negative for BRCA1 and BRCA2 pathogenic mutations. Our analysis revealed the presence of four novel deleterious mutations: c.1186insT, c.1857delT and c.2850delC in three cases, c.3418dupT in one control. In addition, we identified two in-frame insertion/deletion, 19 missense substitutions (two of them predicted as pathogenic), 9 synonymous variants, 28 variants located in introns and 2 in UTRs, as well as frequent variants. Truncating PALB2 mutations were found in 0.36% of familial breast cancer cases, a frequency lower than the one detected in comparable studies in other populations (0.73-3.40%). This suggests a small but significant contribution of PALB2 mutations to the breast cancer susceptibility in the French population. PMID- 26564481 TI - The spectrum of BRCA1 and BRCA2 alleles in Latin America and the Caribbean: a clinical perspective. AB - Hereditary cancer predisposition gene testing allows the identification of individuals at high risk of cancer that may benefit from increased surveillance, chemoprevention, and prophylactic surgery. In order to implement clinical genetic strategies adapted to each population's needs and intrinsic genetic characteristic, this review aims to present the current status of knowledge about the spectrum of BRCA pathogenic variants in Latin American populations. We have conducted a comprehensive review of 33 studies published between 1994 and 2015 reporting the prevalence and/or spectrum of BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variants. The combined sample size for these studies consisted of 4835 individuals from 13 countries in Latin America and the Caribbean, as well as in Hispanics in the United States. A total of 167 unique pathogenic variants have been reported in the existing literature. In unselected breast cancer cases, the prevalence ranged from 1.2 to 27.1%. Some countries presented a few recurrent pathogenic variants, while others were characterized by diverse, non-recurrent variants. The proportion of BRCA pathogenic variants shared between Hispanics in the United States and Latin American populations was estimated at 10.4%. Within Latin America and the Caribbean, 8.2% of the BRCA variants reported were present in more than one country. Countries with high prevalence of BRCA pathogenic variants may benefit from more aggressive testing strategies, while testing of recurrent variant panels might present a cost-effective solution for improving genetic testing in some, but not all, countries. PMID- 26564483 TI - Anisotropy of Solid Breast Lesions in 2D Shear Wave Elastography is an Indicator of Malignancy. AB - RATIONALE AND OBJECTIVES: To investigate if anisotropy at two-dimensional shear wave elastography (SWE) suggests malignancy and whether it correlates with prognostic and predictive factors in breast cancer. MATERIALS AND METHODS: Study group A of 244 solid breast lesions was imaged with SWE between April 2013 and May 2014. Each lesion was imaged in radial and in antiradial planes, and the maximum elasticity, mean elasticity, and standard deviation were recorded and correlated with benign/malignant status, and if malignant, correlated with conventional predictive and prognostic factors. The results were compared to a study group B of 968 solid breast lesions, which were imaged in sagittal and in axial planes between 2010 and 2013. RESULTS: Neither benign nor malignant lesion anisotropy is plane dependent. However, malignant lesions are more anisotropic than benign lesions (P <= 0.001). Anisotropy correlates with increasing elasticity parameters, breast imaging-reporting and data system categories, core biopsy result, and tumor grade. Large cancers are significantly more anisotropic than small cancers (P <= 0.001). The optimal anisotropy cutoff threshold for benign/malignant differentiation of 150 kPa(2) achieves the best sensitivity (74%) with a reasonable specificity (63%). CONCLUSIONS: Anisotropy may be useful during benign/malignant differentiation of solid breast masses using SWE. Anisotropy also correlates with some prognostic factors in breast cancer. PMID- 26564482 TI - LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer. AB - Long non-coding RNAs (lncRNAs) are a class of newly recognized DNA transcripts that have diverse biological activities. Dysregulation of lncRNAs may be involved in many pathogenic processes including cancer. Recently, we found an intergenic lncRNA, LINC00472, whose expression was correlated with breast cancer progression and patient survival. Our findings were consistent across multiple clinical datasets and supported by results from in vitro experiments. To evaluate further the role of LINC00472 in breast cancer, we used various online databases to investigate possible mechanisms that might affect LINC00472 expression in breast cancer. We also analyzed associations of LINC00472 with estrogen receptor, tumor grade, and molecular subtypes in additional online datasets generated by microarray platforms different from the one we investigated previously. We found that LINC00472 expression in breast cancer was regulated more possibly by promoter methylation than by the alteration of gene copy number. Analysis of additional datasets confirmed our previous findings of high expression of LINC00472 associated with ER-positive and low-grade tumors and favorable molecular subtypes. Finally, in nine datasets, we examined the association of LINC00472 expression with disease-free survival in patients with grade 2 tumors. Meta-analysis of the datasets showed that LINC00472 expression in breast tumors predicted the recurrence of breast cancer in patients with grade 2 tumors. In summary, our analyses confirm that LINC00472 is functionally a tumor suppressor, and that assessing its expression in breast tumors may have clinical implications in breast cancer management. PMID- 26564484 TI - [Clinical aspects at the heart of hospital violence]. PMID- 26564485 TI - [Health democracy, a utopia?]. PMID- 26564487 TI - [(Community) psychiatry, a parenthesis?]. AB - Beyond an a priori antagonism between these two notions, alienism and mental health cultivate analogies as to the place to which they assign mental health. Is community psychiatry not therefore simply a parenthesis in the history of psychiatry? The question is raised therefore regarding the place given to subjectivity and complexity. What must be done to ensure that this parenthesis of community psychiatry does not close? It is perhaps a case of making use of the tools which institutional psychotherapy has developed to keep the community psychiatry spirit alive. PMID- 26564486 TI - [Everyday practice in psychiatry and the politics of civilisation]. AB - Daily clinical practice confronts us not only with the clinical aspect but also with the political. Political orientation has a direct impact on the way in which we carry out this clinical practice, as well as on the place of those who are outside the system. The politics of civilisation are therefore an option in the face of neoliberalism. PMID- 26564488 TI - [Work in psychiatry: a political question]. AB - In the experience of Saint Alban, therapeutic work is a major focus of institutional psychotherapy. What is the place today of work in the therapeutic projects led by caregivers? The principle of reality concerning our society clashes with the importance which the caregiving team attaches to work as a principle of reintegration. New opportunities for sociability and integration must be designed and bridges must be co-constructed by nurses and patients towards associations and activities in the community. PMID- 26564489 TI - [An insane dialogue]. AB - How should madness and in particular delusional manifestations be considered? The caregiver's perception of delirium has an impact on how they view the function of the caregiver in psychiatry. Should delirium be suppressed? Delirium is an individual phenomenon but the themes are linked to social issues. Must we not take into account everyone's "thresholds" with regard to the place of delirium, in order to make it part of "living together". Two patients of a psychiatric care system discuss these issues. PMID- 26564490 TI - [Jean Oury, "I am a poumista"]. AB - If being a poumista means considering that people disalienate themselves by revolutionising the world, being a poumista psychiatrist consists in taking into consideration psychological alienation and social alienation. Hence the importance of hospital committees and clubs, to give back to patients the status of a subject and to understand the question of hierarchy. The caregiver in psychiatry must bear in mind that one of the essential dimensions of their work is to "make do with" schizophrenic patients and that they must engage in everyday acts. PMID- 26564491 TI - [The Other, the object and the social connection]. AB - The Occupy Abay movement was formed in Moscow in a context of anomie. This Russian opposition movement consisted in gatherings of strangers, without any predefined ideology, the tacit objective possibly being a civilizing project. The experience of the Scratch orchestra brought together nonprofessional musicians whose performances could be linked to political acts. The psychiatric institution brings people together; it must be able to offer a response to patients' suffering. The choice of working together through multi-person practice is an option. It is based on the fact of accepting, like the two movements cited above, the "lack of a master". PMID- 26564492 TI - [The relationship, a key ingredient of care]. AB - The quality of the relationship or the therapeutic alliance is one of the common factors for predicting the success or failure of therapy. How is this relationship built, and on what bases? Two fundamental questions to which the answer lies in the facilitating aptitudes of anyone working in a help and/or care relationship. PMID- 26564493 TI - [Operational fatigue: debriefing from Kapisa, Afghanistan]. AB - The concept of operational fatigue, a term first used during the Second World War, was subsequently extended to encompass a vague series of psychological disorders. This article looks back at an overseas operation in Afghanistan, during the summer of 2011, where the tense background situation, casualties and fatalities resulted in some members of the commando parachute units suffering from such conditions. PMID- 26564495 TI - Steering Metallofullerene Electron Spin in Porous Metal-Organic Framework. AB - Paramagnetic endohedral fullerenes are ideal candidates for quantum information processing and high-density data storage due to their protected spins with particularly high stability. Herein, we report a solid spin system based on a paramagnetic metallofullerene Y2@C79N through incarcerating it into the cage shaped pores of a metal-organic framework (MOF-177). In this kind of guest and host complex, the Y2@C79N molecules inside the pores of MOF crystal show axisymmetric paramagnetic property. It was found that the pores of MOF-177 crystal play an important role in dispersing the Y2@C79N molecules as well as in steering their electron spin. The group of arranged Y2@C79N molecules and their electron spins in MOF crystals are potential quantum bits for quantum information science and data storage. Moreover, this kind of solid spin system can be used as a probe for nanoscale nuclear magnetic resonance or for motion imaging of a single biomolecule. PMID- 26564496 TI - Centrosymmetric and chiral porous thorium organic frameworks exhibiting uncommon thorium coordination environments. AB - The solvothermal reaction of thorium nitrate and tris-(4-carboxylphenyl)phosphine oxide in DMF affords a centrosymmetric porous thorium organic framework compound [Th(TPO)(OH)(H2O)].8H2O (1). In contrast, the ionothermal reaction of the same reagents in the ionic liquid 1-butyl-2,3-dimethylimidazolium chloride results in the formation of a rare example of a chiral and porous thorium organic framework compound, [C9H17N2][Th(TPO)Cl2].18H2O (2), which is derived solely from achiral starting materials. The geometries of the Th(iv) centers in compounds 1 and 2 are both atypical for low valent actinides, which can be best described as a ten coordinate spherical sphenocorona and an irregular muffin, respectively. A large cavity of 17.5 A (max. face to face) * 8 A (min. face to face) with a BET surface area of 623 m(2) g(-1) in compound 2 is observed. The poor stability indicated by thermal gravimetric analysis and the water-resistance test for compound 2 may be due to the unique anisotropic coordination geometry for thorium. Temperature dependent luminescence studies for both compounds indicate that the trends in the intensity vary as the Th-Th distance and the coordination environments of Th(iv) centers change. PMID- 26564497 TI - [Dynamic Changes of the Quantitative Distribution,Apoptosis and Proliferation of T and B Cells in the Skin of KM Mutant Mice]. AB - OBJECTIVE: To observe the change of quantitative distribution,apoptosis and proliferation of T and B cells in the skin of KM mutant mice. METHODS: We chose 1 ,3-,6-,9-,22-day,3-,6-month-old KM mutant and wild-type mice to detect the changes of T and B lymphocytes using blood routine tests and immunohistochemical staining. Apoptosis was detected by TUNEL staining and proliferation by proliferating cell nuclear antigen (PCNA) staining. RESULTS: T cells on KM mutant mice skin were mainly seen in epidermis and dermis. They increased on the first day to 6(th) day after birth and decreased on the 9(th) and 22(nd) day,but after 3-month-old,their number began to increase;at the time of 6 months,the number of B cells also increased. The apoptosis of the skin hair follicle and sebaceous gland cells were more obvious in KM mutant mice than in wild-type mice,with the maximal apoptosis occurred at the age of 22-day-old in both groups. The proliferation of epidermal basal cells in KM mutant mice between 1 to 9-day-old was not significantly different from that in the wild-type mice,but decreasing on the 22(nd) day and 3(rd) month and increasing in the 6(th) month. The proliferation in hair follicle and sebaceous glands decreased on 9(th) day,increased on 22(nd) day,and deceased on the 3(rd) month again. CONCLUSIONS: The quantitative distribution,apoptosis,and proliferation of T and B lymphocytes abnormally change in the skin tissue of KM spontaneous mutant mice. They may lead to immune and hair growth disorders and promote the inflammatory responses. PMID- 26564498 TI - [Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice]. AB - OBJECTIVE: To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. METHODS: Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. RESULTS: The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 +/- 3.3141)0/00 to (28.1667+/-4.1345)0/00 (P=0.033) and from (76.5000 +/- 4.6242)0/00 to (22.8333 +/- 3.6553)0/00(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). CONCLUSION: S-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation. PMID- 26564499 TI - [Regulatory Role of Nitric Oxide in Development and Hatching of Mouse Blastocysts]. AB - OBJECTIVE: To determine the regulatory role and mechanism of nitric oxide (NO) in the development and hatching of mouse blastocysts. METHODS: The Kunming female mice were superovulated and then mated with mature male mice. On the day 2.5 of their pregnancy, morulae were flushed from their uterine horns with culture media. Morulae were cultured in different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), or the combination of L-NAME and SNP in culture media for 48 hours. The development and hatching of blastocysts were examined on day 4 and day 5 and the total numbers of blastocyst cells and cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope. RESULTS: With the increase of the concentration of L-NAME or SNP, the hatching rate of blastocysts and the total number of blastocyst cells were significantly reduced. The addition of 10 nmol/L SNP in culture media with 5 mmol/L L-NAME significantly increased the development of blastocysts and promoted hatching of blastocysts. However, with increase of SNP concentration in culture media with 5 mmol/L L-NAME, the development and hatching rates of blastocysts were significantly decreased. L-NAME had no obvious effect on the expression of active caspase 3 in blastocyst cells. However,when being above 500 nmol/L,SNP significantly increased the expression of caspase 3 in blastocyst cells. CONCLUSIONS: NO plays an important role in development and hatching of mouse blastocysts. Excessively high or low NO can damage the division of blastomeres, resulting in the failure of the blastocyst development and hatching. Also, excessively high NO can lead to the apoptosis of the blastocyst cells. PMID- 26564500 TI - [Change of Ankyrin G Promoter Activity Following Treatment with Sodium Valproate at Different Concentrations]. AB - OBJECTIVE: To investigate whether sodium valproate (VPA) directly regulates the activity of Ankyrin G(AnkG) promoter in vitro. METHODS: The mouse AnkG promoter sequence was identified by comparing both human and mouse AnkG promoter sequences. The promoter was amplified from C57BL/6 mouse genome DNA and cloned into pGL3 Luciferase reporter vector. The Luciferase activity was detected in N2a and 293T cells and then treated with 0,0.5, and 1 mmol/L VPA for 12 h. The transcription activity of AnkG promoter in cells and the activity of VPA-treated Luciferase reporter vector in cells were detected using dual Luciferase reporter assay. RESULTS: The AnkG promoter clone and its expression vector were successfully established, as confirmed by enzyme digestion and sequencing. The AnkG promoter showed high transcription activity in both N2a and 293T cells. The Luciferase activity was significantly induced following 0.5 mmol/L VPA treatment in both N2a and 293T cells. CONCLUSIONS VPA can up-regulate the AnkG expression via directly increasing its transcription activity. Thus, the in vivo AnkG expression may be directly regulated by the VPA at transcriptional level. PMID- 26564501 TI - [miR-29b Reduces Cisplatin Resistance of Gastric Cancer Cell by Targeting PI3K/Akt Pathway]. AB - OBJECTIVE: To investigate the regulatory effect of miR-29b on gastric cells' resistance to cisplatin. METHODS: The expression of miR-29b in gastric cancer cell line treated with cisplatin concentration gradient was detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. CCK8 was used to measure the cell viability after cisplatin treatment in condition of miR-29b knock-down and overexpression. RESULTS: The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AKT2 was downregulated. The up-regulation of miR-29b enhanced the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b enhanced the cisplatin resistance. Rescue experiments demonstrated that the miR 29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3K/Akt pathway. The expressions of the other two members of miR-29 family, miR 29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin. CONCLUSION: miR-29b can enhance the sensitivity of S gastric cancer cell by directly targeting PI3K/Akt pathway. PMID- 26564502 TI - [Growth Differentiation Factor 15 Inhibits Elevated Expression of Matrix Metalloproteinase 1 Induced by Pooled Serum in Patients with Coroanry Artery Ectasia]. AB - OBJECTIVE: To observe the effects of coroanry artery ectasia (CAE) patients' pooled serum on the main proteinases and extracellular matrix (ECM) synthesis and explore whether the growth differentiation factor 15(GDF 15) can regulate the characteristic changes induced by CAE patients' pooled serum. METHODS: Serum samples were collected from 32 CAE patients, 30 patients with coronary heart disease (CHD), and 31 subjects with normal coronary arteries (CON) and then mixed in the same volumes by groups. Then human umbilical vein smooth muscle cells were cultured with the media containing 25% pooled serum. After having been disposed, proteinase system and ECM synthesis system were detected in the cell and culture media samples. GDF15 or GDF15 antibodies was added into the 25% pooled serum in each group to observe if GDF 15 could impact the characteristic changes induced by CAE patients' pooled serum. RESULTS: The expression of matrix metalloproteinases (MMP) 1 mRNA in CAE group was significantly higher than CON group (P=0.002) and CHD group (P=0.000), the secretory MMP1 protein and total MMPs activity in culture media were also upregulated in CAE group (both P<0.01). After adding GDF 15 into the culture media (GDF15+CAE group), the MMP1 mRNA ,secretory MMP1 protein, and total MMPs activity were significantly lower than CAE group (all P<0.01), while in the GDF15 antibody+CAE group, the MMP1 mRNA and total MMPs activities were significantly higher than in GDF15+CAE group (both P<0.01), but the secretory MMP1 protein was not different from GDF 15+CAE group (P>0.05). CONCLUSION: The vascular smooth muscle cells may participate in the CAE process mainly by regulating MMPs system but not the elastase 2 or ECM synthesis system, and GDF15 may be an compensatory factor to prohibit the over-destruction of coronary ECM induced by MMPs. PMID- 26564503 TI - [Chronic Disease Control among Rural Residents in Beijing Pinggu District]. AB - OBJECTIVE: To analyze the composition and control status of chronic diseases among rural residents in a Beijing suburb district. METHODS: Rural residents aged 35 years or older were investigated by stratified random sampling in Pinggu District, Beijing. Each participant received questionnaire-based survey,physical examination,and laboratory tests including routine blood test,urine albumin creatinine ratio (ACR), liver and renal function,serum lipid, fasting blood glucose, and glycosylated hemoglobin. RESULTS: A total of 10 385 residents completed all items. Cerebrovascular disease was leading cause of hospitalization (accounting for 14.4%) and its incidence in the population was 9.6%. The incidences of hypertension,hyperlipidemia,diabetes mellitus,and gout/hyperuricemia,which were the main compositions related with metabolic diseases,were up to 64.4%,42.5%,24.4%, and 9.0%, respectively. The disease onset was significantly related with the age. The incidence of hypertension was gradually elevated with the increasing of age,while the peak age was 55-64 years for diabetes and 35-44 years for gout/hyperuricemia. The awareness rate of hypertension,diabetes,and chronic kidney disease was 60.2%, 55.1%,and 6.0%,respectively. The control rate of chronic disease was 19.2% and 28.8% in hypertensive and diabetic patients, respectively. CONCLUSIONS: Cerebrovascular diseases and metabolic-associated diseases are the main chronic diseases affecting rural residents in Pinggu district, Beijing. The awareness rate and control rate of chronic diseases needs to be further enhanced by strengthening health education and improving the community medical service. PMID- 26564504 TI - [Natural Outcome of Genital Tract High-risk Human Papillomavirus Infection and Associated Factors among 760 Women]. AB - OBJECTIVE: To investigate the natural outcome of genital tract high risk human papillomavirus (HR-HPV) infection and associated factors among women in Xi'an region. METHODS: Totally 760 women with primary genital tract HR-HPV infection were enrolled and followed up by HPV-DNA genotyping technology. The cervical cytological techniques and/or colposcopy were used when necessary. RESULTS: Among these subjects,the natural clearance rate of HR-HPV infection was 71.58%,with the median time of 8.10 months. The rate of HPV persistent infection was 22.63%, with the median time of 17.23 months. The rate of progression to cervical intraepithelial neoplasia (CIN)/cervical cancer (CC) was 5.79%, with the median time of 29.34 months. The natural clearance rate (P=0.000), persistent infection rate (P=0.000) and progression rate (P=0.040) in women older than 50 years were statistically difference from other age groups. The persistent infection rate in multiple infections group was significantly lower than that in single infection group (P=0.010), with the median time statistically longer than that in single infection group (P=0.018). The most easily progressive genotypes were HPV-16,HPV 33, HPV-58,HPV-18,HPV-52, and HPV-68, among which HPV-16 was the most common genotype in CIN 3/CC cases, accounting for 85.00%. CONCLUSIONS: Most of HR-HPV infections are naturally cleared within 2 years, and only a few cases progresses to CIN/CC. Women older than 50 years have a lower natural clearance rate and higher persistent and progressive rates. Multiple infections can affect the persistent infection. HPV-16 is the most common carcinogenic genotype in Xi'an region. PMID- 26564505 TI - [Risk Factors of Perioperative Cardiac Events in Elderly Patients with Coronary Heart Disease Undergoing Non-cardiac Surgery]. AB - OBJECTIVE: To identify the incidence and risk factors of perioperative major adverse cardiac events (MACE) in elderly patients with coronary heart disease (CHD) undergoing non-cardiac surgery. METHODS: We prospectively analyzed the clinical data of 360 CHD patients who aged 75 years or older undergoing elective intermediate-to high-risk surgery in five medical centers across China from January 2008 to January 2010. The clinical variables included the 12-lead ECG and Troponin I levels after surgery. The combined outcome was defined as all the perioperative MACE in hospital. The risk factors of MACE and their indexes were analyzed with univariate analysis and multivariable logistic regression in SPSS software,together with a risk scoring and stratification system established. RESULTS: Perioperative MACE occurred in 11.94% of elderly CHD patients undergoing non-cardiac surgery. Seven independent risk factors of perioperative MACE for this population were identified,which included angina within 6 months (P=0.001), hypertension(P=0.014), preoperative haematocrit (HCT) <40% (P=0.050), serum creatinine (Scr)>150 mmol/L (P=0.014), ejection fraction(EF) <50% (P=0.019), intraoperative hyoxemia (P=0.019), and operative time>150 min (P=0.001). The risk indexes of these factors were 4,3,3,6,4,5, and 4, respectively. The rate of perioperative MACE increased significantly as the level of risk stratification elevated. CONCLUSIONS: Elderly CHD patients undergoing non-cardiac surgery are at high risk of perioperative MACE. Angina within 6 months,hypertension, preoperative HCT<40%, Scr>150 mmol/L, EF<50%, intraoperative hyoxemia, and operative time>150 min can increase the risk of MACE. The risk scoring and stratification system based on the risk factor index can be a valuable parameter for assessing the perioperative cardiac risk of noncardiac surgery for elderly CHD patients. PMID- 26564506 TI - [Prognostic Factors of Stage 3 Colorectal Cancer in 433 Patients]. AB - OBJECTIVE: To summarize the prognostic factors of stage 3 colorectal cancer. METHODS: The clinical data of 433 patients with stage 3 colorectal cancer who were admitted to our hospital from January 2005 to December 2008 for radical surgery and adjuvant chemotherapy were retrospectively analyzed. Relationship of their clinicopathologic features and treatment with the prognosis were analyzed. RESULTS: Of these 433 stage 3 patients,the mean disease-free survival was (72.37 +/- 2.11) months and mean overall survival was (79.91 +/- 2.02) months; however, the median survival times were not reached. The 1-,3-, and 5-year disease-free survival rate were 86.8%,77.9%, and 57.0% and the overall survival rate were 91.5%,75.1%, and 63.3%. Multivariate COX regression analysis displayed that intestine obstruction before surgery, complications after surgery,tumor location,positive surgical margin, neural cell infiltration,vessel cancer embolus, TNM stage, lymph node ratio, adjuvant chemotherapy regimens, and chemotherapy duration were the independent factors affecting disease-free and overall survivals in patients with stage 3 colorectal cancer. The efficacies of FOLFOX and XELOX regimens were significantly correlated with patient's age, complications,tumor location,and chemotherapy duration. CONCLUSIONS: Complications,tumor location, TNM stage, and positive surgical margin are the independent prognostic factors of stage 3 colorectal cancer. FOLFOX and XELOX regimen can remarkably improve prognosis,and a longer duration of chemotherapy can achieve better survival. PMID- 26564507 TI - [Logistic Regression Analysis of Depression in Arteriosclerosis Obliterans Patients and Its Risk Factors]. AB - OBJECTIVE: To investigate the depression in arteriosclerosis obliterans (ASO) patients and its risk factors. METHODS: The self-rating depression scale (SDS) was applied in 228 ASO patients hospitalized in the vascular surgery department of Peking Union Medical College Hospital from March 2010 to October 2011. The risk factors of depression were analyzed by using univariate and multivariate Logistic regression analysis. RESULTS: Of these 228 ASO patients, 133 (58.3%) were found to be depressive. Univariate and multivariate analysis showed that female (OR=0.15,95% CI:0.05-0.45), hypertension (OR=4.63,95% CI:1.90-11.29), coronary heart disease (OR=3.62,95%CI:1.43-9.18), as well as Fontaine 2a (OR=20.76,95% CI:3.21-134.28), 2b (OR=26.34,95% CI:4.20-164.97), 3(OR=192.28,95% CI:25.97-1423.51), and 4(OR=291.41,95% CI:28.67-2962.21) were the risk factors of depression in ASO patients. CONCLUSIONS: ASO patients can easily develop depression. Female, hypertension, coronary heart disease, and Fontaine 2a, 2b,3,and 4 are the risk factors of depression in ASO patients. PMID- 26564508 TI - [Application of Immunohistochemistry and Immunofluorescence Staining in Detection of Phospholipase A2 Receptor on Paraffin Section of Renal Biopsy Tissue]. AB - OBJECTIVE: To evaluate the application of immunohistochemistry and fluorescence staining method in the detection of phospholipase A2 receptor (PLA2R) on paraffin section of renal biopsy tissue,and to find an accurate and fast method for the detection of PLA2R in renal tissue. METHODS: The PLA2R of 193 cases were detected by immunohistochemical staining,and the antigen was repaired by the method of high pressure cooker (HPC) hot repair plus trypsin repair. The 193 samples including 139 cases of idiopathic membranous nephropathy (IMN), 15 cases of membranous lupus nephritis, 8 cases of hepatitis B virus associated membranous nephropathy, 18 cases of IgA nephropathy, and 13 cases of minimal change diseases. To compare the dyeing effects, 22 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 4 different. METHODS: of antigen repairing,which included HPC hot repair, HPC hot repair plus trypsin repair, water bath heat repair, and water bath heat repair plus trypsin repair. To compare the dyeing effects, 15 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 3 different. METHODS: of antigen repairing,which included water bath heat repair plus trypsin repair, protease K digestion repair, and pepsin digestion repair. RESULTS: In 193 cases, the positive rate of PLA2R in IMN cases was 90.6% (126/139), and the other 54 patients without IMN were negative. Twenty-two IMN patients were positive for PLA2R by using the HPC heat repair plus trypsin repaire or the water bath heat repair plus trypsin repair;while only a few cases of 22 IMN cases were positive by using the HPC hot repair alone or water bath heat repair alone. Fifteen IMN patients were positive for PLA2R by using water bath heat repair plus trypsin repair,protease K digestion repair,and pepsin digestion repair, but the distribution of positive deposits and the background were different. CONCLUSIONS: PLA2R immunohistochemical staining can effectively identify IMN and secondary MN. For immunohistochemical staining and immunofluorescence staining, the preferred method of antigen repair is water bath heat repair plus trypsin repair. PMID- 26564509 TI - [Three-dimensional Pseudo-continuous Arterial Spin Label Non-contrast Enhanced Perfusion Imaging of Head and Neck Tumors with High-field MR System]. AB - OBJECTIVE: To evaluate the feasibility of three-dimensional pseudo-continuous arterial spin label (3D pCASL) non-contrast enhanced perfusion imaging applied to head and neck tumors in high-field MR and detect the effects of different postlabeling delay (PLD) time on image quality and the reliability of repeated measurements of tumor blood flow (BF) in different 3D pCASL groups. METHODS: In this prospective study,all the 25 patients received neck 3D pCASL non-contrast enhanced perfusion examinations in a 3.0 T MR system by using an 8-channel head and neck joint coil. Conventional T1-weighted (TIWI) and T2-weighted imaging (T2WI) were performed firstly. Finally,three 3D pCASL with different PLD time [ASL1(PLD1=1525 ms),ASL2 (PLD2=2025 ms), ASL3(PLD3=2525 ms)] were acquired. Patients' perfusion-weighted images acquired from different 3D pCASL sequences underwent the analysis of signal to noise ratio (SNR) and contrast noise ratio (CNR) for tumors. Two observers performed the qualitative assessments on spiral artifacts and vascular artifacts of perfusion-weighted images from different 3D pCASL sequences. Blood flow (BF) of tumors from different 3D pCASL sequences were measured by the two observers respectively for the first time and by observer 2 for the second time. RESULTS: Seventeen enrolled patients (age:50.1 +/- 12.7 years,M/F=10:7) with histopathologic. RESULTS: underwent the evaluation of image quality and measurements of BF values. The SNRs and CNRs of ASL1,ASL2, and ASL3 showed a descending trendency. SNRs (P=0.011) and CNRs (P=0.009) of ASL1 were significant higher than those of ASL3. There was no significant difference of scores of spiral artifacts among the three ASL groups (P=0.932). The scores of vascular artifacts of ASL1,ASL2,and ASL3 showed a descending trendency,also. And scores of ASL1 was significant higher than that of ASL3(P=0.000). The intraclass correlation coefficient (ICC) of intre-and intraobserver were high (ICC>0.9). Although the BF values of ASL1,ASL2, and ASL3 showed an ascending trendency,there was no significant difference among the three groups (P=0.977). CONCLUSIONS: The 3D pCASL no-contrast enhanced perfusion MR imaging can be used for head and neck tumor. The image quality of perfusion weighted images and reliability of BF measurements were satisfied. The 3D pCASL series with PLD of 1525 ms and 2025 ms have better image quality than PLD of 2525 ms. And BF values do not show significant statistic difference among the three groups. Therefore, 3D pCASL series with PLD of 1525 ms and 2025 ms are more suitable for the perfusion imaging of head and neck tumors PMID- 26564510 TI - [Hyperechoic Breast Lesions on Ultrasound:Easily Misdiagnosed Conditions]. AB - OBJECTIVE: To evaluate the incidences of hyperechoic breast lesions and hyperechoic breast cancers in lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 on ultrasound and investigate their sonographic features and the underlying histological causes. METHODS: The pathologic records for 848 sonographically guided core needle biopsies or surgical resection were retrospectively reviewed from June 2012 to March 2014. Hyperechoic lesions were identified and their sonographic features were evaluated. The incidence of hyperechoic breast lesions and the frequency of hyperechoic cancers among all hyperechoic breast lesions were calculated. RESULTS: Of all 848 lesions, 0.9% (8/848) were hyperechoic. Twenty-five percent (2/8) of the hyperechoic lesions were malignant and the remaining six were benign. Among the 280 malignant lesions, 0.7%(2/280) were hyperechoic. The pathological basis of breast lesions presenting as hyperechoic nodules included inflammatory edema, galactoceles, and grit calcifications. Little difference of sonographic feature was found between benign and malignant hyperechoic lesions in this study. CONCLUSIONS: Hyperechoic breast lesions are rare conditions but can be associated with a high ratio of breast cancer. History-taking and imaging techniques may help to avoid misdiagnosis. PMID- 26564511 TI - [Use of Ultrasound in the Follow-up of Professional Athletes Receiving Conservative Treatment of Patellar Tendon Enthesiopathy]. AB - OBJECTIVE: To investigate the role of high-frequency ultrasound (HFUS) in evaluating in the effectiveness of conservative treatment for professional athletes with patellar tendon enthesiopathy. METHODS: According to different treatment intensities, 24 professional athletes with patellar tendon enthesiopathy were randomly divided into painless group, slightly-painful group and extremely-painful group. Then changes of the HFUS findings [including ranges of two-dimensional diseases and blood conditions by Color Doppler Flow Imaging (CDFI)] of patellar tendon before and after the treatment were recorded. The results were also compared with conventional clinical treatment evaluations. RESULTS: After two courses of treatment,the percentage of athletes whose pain was resolved or disappeared was 37.5% in painless group, 87.5% in slightly-painful group, and 62.5% in extremely-painful group. The pain score was 4.50 +/- 2.07, 4.88 +/- 1.13, and 6.13 +/- 1.55 in painless group,slightly-painful group,and extremely-painful group, respectively,before treatment and 4.88 +/- 2.17, 3.00 +/ 1.77,and 5.13 +/- 2.36 after treatment. The average pain score remarkably decreased in the slightly-painful group and extremely-painful group,and such difference was statistically significant in the slightly-pain group (P<0.05). The effective rate (defined as thinner patellar,decreased hypoecho area and fewer blood distribution in the lesion) was 38%, 50%, and 62% in the painless group, slightly-painful group,and extremely-painful group, and the rates in the slightly painful group and extremely-painful group were significantly higher than that in painless group (both P<0.05). CONCLUSIONS: HFUS can display the ultrasonographic changes of patellar tendon enthesiopathy after conservative treatments in an objective and quantitative manner. Compared with conventional clinical evaluations, it can more accurately reflect the disease recovery status. PMID- 26564512 TI - [Clinical Value of Ultrasonography in Predicting Massive Hemorrhage during Cesarean Scar Pregnancy]. AB - OBJECTIVE: To investigate the clinical value of ultrasonography in predicting massive haemorrhage during Cesarean scar pregnancy. METHODS: The clinical and ultrasonograhic data of 119 Cesarean scar pregnancy patients were retrospective analyzed. According to the amount of bleeding, these patients were divided into two groups:massive hemorrhage group and non-massive hemorrhage group. The potential risk factors of massive hemorrhage were analyzed with Logistic regression analysis. RESULTS: The size and type of lesions, flow grade, and residual muscular thickness were screened as the risk factors of massive haemorrhage by Logistic regression model. When P=0.3 was applied as the cutoff value,the diagnostic accuracy was 90.75%;meanwhile,the sensitivity,specificity,positive predictive value, and negative predictive value were 88.23%, 91.76%, 81.08%, and 95.12%,respectively. CONCLUSION: Ultrasonography can accurately predict the risk of massive hemorrhage during the Cesarean scar pregnancy. PMID- 26564513 TI - [Effect of Selenious Yeast Tablets on the Thyroglobulin Antibody Level in ThyroglobulinAntibody-positive Patients with Differentiated Thyroid Cancer]. AB - OBJECTIVE: To investigate the change of thyroglobulin antibodies (TgAb) after the application of selenious yeast tablet (SYT) in differentiated thyroid cancer (DTC) patients with positive TgAb (>115 U/ml). METHODS: We enrolled 41 DTC patients with positive TgAb who had undergone total thyroidectomy and subsequent 131I therapy as well as applied SYT in group 1 (G1). Patients with an interval of more than 6 months between SYT use and 131I therapy or with repeated TgAb measurements before the use of SYTs were divided into group 2 (G2) and group 3 (G3), respectively. Changes in TgAb after application of SYT in both G1 and G2 were observed and analyzed by rank sum test. Comparison of TgAb gradient over certain time before and after the application was analyzed by t-test. RESULTS: The proportions of patients with decreased or elevated TgAb were 85.4% and 14.6% in G1 and 90.9% and 9.1% in G2, respectively. Compared with the previous TgAb levels, TgAb decreased significantly after the application of SYT in either G1 (P=0.000) or G2(P=0.003). In G3, the TgAb level rose by 5.6% every month before applying SYT and fell 8.3% every month after the application (P=0.086). CONCLUSION: Application of SYT in DTC patients with positive TgAb can effectively decrease the TgAb level. PMID- 26564514 TI - [Low-dose Radioiodine for Ablation in Non-metastatic High-risk Thyroid Cancer]. AB - OBJECTIVE: To evaluate the role of low-dose radioiodine in the treatment of non metastatic high-risk differentiated thyroid cancer (DTC) patients with macroscopic extra-thyroidal extension (MAEE). METHODS: Totally 103 DTC patients with total/near-total thyroidectomy and selective lymph node resection, and with MAEE, any N stage,preablative stimulated thyroglobulin (ps-Tg) <= 5 ng/ml when thyroglobulin antibodies (TgAb) <= 46 U/ml and no evidence of distant metastasis were retrospectively analyzed in this study. Fifty-two received low dose RAI (1110 MBq) and 51 received high dose (>= 3700 MBq). The successful ablation rate and disease-free survival rate were compared between these two groups. RESULTS: The successful ablative rate was 86.5% (45/52) in low-dose group and 86.3% (44/51) in high-dose group (P=0.9688), and the disease-free survival was 97.4% (38/39) in low-dose group and 97.5% (39/40) in high-dose group. CONCLUSION: The ablation success and medium-term clinical outcome with low-dose RAI is proved to be non-inferior to high dose in non-metastatic patients with MAEE when ps-Tg level is less than 5 ng/ml. PMID- 26564515 TI - [Features of Acquired Immunodeficiency Syndrome-related Lymphoma on (18)F fluorodeoxyglucose Positron Emission Tomography/Computed Tomography]. AB - OBJECTIVE: To analyze the imaging features of (18)F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)/computed tomography (CT) in acquired immune deficiency syndrome-related lymphoma (ARL) patients correlated with their clinical signs, symptoms, and treatments. METHODS: Five ARL patients underwent 18F-FDG PET/CT at Peking Union Medical College Hospital from October 2008 to January 2013. Two patients received two additional follow-up studies 6 months later. RESULTS: Among these 5 patients, 18FDG-PET/CT helped in diagnosis of two patient and changed therapeutic strategy in other two patients. In two patients underwent 18F-FDG PET/CT brain scans, low-metabolism lesion was newly found in cerebral cortex. Of 4 patients receiving highly active antiretroviral therapy, PET/CT also demonstrated diffusely elevated 18F-FDG uptake in subcutaneous adipose tissue in two patients. CONCLUSION: 18F-FDG PET/CT is a highly useful tool in the diagnosis and treatment of ARL patients, in particular in the identification of associated encephalopathy and lipodystrophy. PMID- 26564516 TI - [Ubiquitous Ribonucleic Acid:miRNA is the Ubiquitin of RNA]. AB - Small RNAs, especially microRNAs (miRNAs),widely exist in eukaryotic cells, with their main functions being regulating gene expression and function of target molecules through the degradation of cellular target RNAs by the ribonuclease based system. Ubiquitins and ubiquitin-like proteins are polypeptides that exist in most eukaryotic cells, and their main function is almost to regulate protein level through the degradation of cellular proteins by ubiquitin proteasome system. Small RNAs, including miRNAs,and ubiquitins or ubiquitin-like proteins have similarities in many aspects although small RNAs and ubiquitin or ubiquitin like proteins interact different substrates respectively. Therefore, miRNAs can be defined as ubiquitra (ubiquitous ribonucleic acid, ubiquitra or uRNA), and the other small RNAs can be defined as ubiquitra-like RNA or uRNA-like RNA. The concept of ubiquitra may be applied for explaining the biological essence of small RNAs diversity. PMID- 26564517 TI - [Application of Reporter Gene Labeling in Stem Cell Therapy for Acute Myocardial Infarction]. AB - Stem cell therapy for acute myocardial infarction is drawing great attention. However,the biological behavior and function mechanism of implanted stem cells remain controversial, as well as their clinical benefits. With the development of imaging probes and devices, molecular imaging enables noninvasive, dynamic tracking of stem cells in vivo. In this review, we summarize the use of various markers,especially the technique of reporter gene labeling, in the field of stem cell therapy, and highlight some recent preclinical and clinical achievements. PMID- 26564518 TI - [Research Advances in NLRP3 Inflammasome-related Regulatory Mechanisms]. AB - Inflammasome is one of the pattern recognition receptors whose activation directly relates to the maturity and secretion of proinflammatory cytokines interleukin (IL)-1Beta and IL-18. Thus, it plays an important role in the humoral immunity. A growing number of studies have found that inflammasome has a close relationship with the pathogenesis of various diseases including atherosclerosis,diabetes, and gout. However,the activation of the inflammasome and its specific regulatory mechanisms remain not clear. This article reviews the possible regulatory mechanisms of the inflammasome NLRP3 in terms of oxidative stress, endoplasmic reticulum stress,and autophagy reaction. PMID- 26564519 TI - [Potential Clinical Implications of Circulating Tumor Cells]. AB - The circulating tumor cells (CTCs) are derived from primary or metastatic tumor lesions and can be detected in the peripheral blood. With certain specific features, CTCs can,to certain extent, reflect the progression and invasiveness of tumors. Detection of CTCs may provide a powerful and noninvasive approach for diagnosing neoplastic disease, identifying drug sensitivity, and enabling real time treatment monitoring and prognosis prediction. Improvements in cell isolation and molecular identification will enable a broad range of clinical applications. PMID- 26564522 TI - Commentary on Hobday et al. (2015): Inconsistent results beneath consistent conclusions--the need for a new approach to analysing alcohol availability. PMID- 26564523 TI - Commentary on Lovatt et al. (2015): Lay and standard alcohol epidemiology--rival approaches or the beginnings of a dialogue? PMID- 26564524 TI - Commentary on Niesink et al. (2015): Interpreting trends in tetrahydrocannabinol potency--three stories, one of which may be true. PMID- 26564525 TI - Commentary on Abdolahi et al. (2015): Isolating the role of the insula in drug cravings. PMID- 26564526 TI - 'Dry puff' and electronic cigarettes. PMID- 26564527 TI - Tobacco sponsorship and the Arts. PMID- 26564530 TI - The practicalities of a 'fit-for-purpose' validation. PMID- 26564531 TI - The context-contingent nature of cross-modal activations of the visual cortex. AB - Real-world environments are nearly always multisensory in nature. Processing in such situations confers perceptual advantages, but its automaticity remains poorly understood. Automaticity has been invoked to explain the activation of visual cortices by laterally-presented sounds. This has been observed even when the sounds were task-irrelevant and spatially uninformative about subsequent targets. An auditory-evoked contralateral occipital positivity (ACOP) at ~250ms post-sound onset has been postulated as the event-related potential (ERP) correlate of this cross-modal effect. However, the spatial dimension of the stimuli was nevertheless relevant in virtually all prior studies where the ACOP was observed. By manipulating the implicit predictability of the location of lateralised sounds in a passive auditory paradigm, we tested the automaticity of cross-modal activations of visual cortices. 128-channel ERP data from healthy participants were analysed within an electrical neuroimaging framework. The timing, topography, and localisation resembled previous characterisations of the ACOP. However, the cross-modal activations of visual cortices by sounds were critically dependent on whether the sound location was (un)predictable. Our results are the first direct evidence that this particular cross-modal process is not (fully) automatic; instead, it is context-contingent. More generally, the present findings provide novel insights into the importance of context-related factors in controlling information processing across the senses, and call for a revision of current models of automaticity in cognitive sciences. PMID- 26564533 TI - Out of the shadows: shining a light on children with tuberculosis. PMID- 26564532 TI - Categorical evidence, confidence, and urgency during probabilistic categorization. AB - We used a temporally extended categorization task to investigate the neural substrates underlying our ability to integrate information over time and across multiple stimulus features. Using model-based fMRI, we tracked the temporal evolution of two important variables as participants deliberated about impending choices: (1) categorical evidence, and (2) confidence (the total amount of evidence provided by the stimuli, irrespective of the particular category favored). Importantly, in each model, we also included a covariate that allowed us to differentiate signals related to information accumulation from other, evidence-independent functions that increased monotonically with time (such as urgency or cognitive load). We found that somatomotor regions tracked the temporal evolution of categorical evidence, while regions in both medial and lateral prefrontal cortex, inferior parietal cortex, and the striatum tracked decision confidence. As both theory and experimental work suggest that patterns of activity thought to be related to information-accumulation may reflect, in whole or in part, an interaction between sensory evidence and urgency, we additionally investigated whether urgency might modulate the slopes of the two evidence-dependent functions. We found that the slopes of both functions were likely modulated by urgency such that the difference between the high and low evidence states increased as the response deadline loomed. PMID- 26564534 TI - The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children. AB - In 2010, the World Health Organization revised the recommendations for the treatment of tuberculosis (TB) in children. The major revision was to increase isoniazid, rifampicin and pyrazinamide dosages according to body weight in children. The recommendations for higher dosages are based on consistent evidence from 1) pharmacokinetic studies suggesting that young children require higher dosages than adolescents and adults to achieve desired serum concentrations; and 2) observational studies reporting that the higher dosages would not be associated with increased risk of toxicity in children. However, national tuberculosis programmes faced unforeseen challenges in implementing the revised recommendations. The main difficulty was to adapt the revised dosages for the treatment of children with drug-susceptible TB using available fixed-dose combinations (FDCs). A more suitable FDC for the intensive and continuation phases of treatment has now been developed for planned implementation in 2015. This paper explains the background and rationale for the development of a new FDC tablet for children with drug-susceptible TB. PMID- 26564535 TI - Counting children with tuberculosis: why numbers matter. AB - In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB programmes and academics. For the first time, a number of different groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons why cases in children can go unreported. We discuss the importance of an accurate understanding of burden for identifying problems in programme delivery, targeting interventions, monitoring trends, setting targets, allocating resources appropriately and providing strong advocacy. We briefly review the estimates produced by new analytical methods, and outline the reasons for recent improvements in our understanding and potential future directions. We conclude that while innovation, collaboration and better data have improved our understanding of the childhood TB burden, it remains substantially incomplete. PMID- 26564536 TI - The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective. AB - Simple, quality-assured, child-friendly formulations of existing first-line anti tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products. PMID- 26564537 TI - Pediatric tuberculosis drug market: an insider perspective on challenges and solutions. AB - Representative stakeholders were consulted on how they felt access to pediatric tuberculosis (TB) drugs could be improved. A key recommendation is the development of new child-friendly, adequately dosed formulations with a good shelf life in all climate zones. There is also an urgent need to improve the diagnosis and reporting of children with TB. Manufacturers of pediatric TB medications are to be incentivized through improved coordination among all stakeholders, with streamlined regulatory approvals and increased consumer education on drug and regimen guidelines. Finally, pooled procurement is advised to ensure sustained market supply against affordable prices. PMID- 26564538 TI - From availability to uptake: planning for the introduction of new, child-friendly anti-tuberculosis formulations. AB - BACKGROUND: Assessing the state of country readiness for the introduction of new, child-friendly anti-tuberculosis formulations can highlight potential bottlenecks, facilitate early planning, and accelerate access to appropriate treatment for children with tuberculosis (TB). METHODS: To understand pathways and potential obstacles to the introduction of new pediatric formulations, we performed a desk review of key policy documents and conducted 146 stakeholder interviews in 19 high-burden countries. RESULTS: Issuance of World Health Organization (WHO) guidance serves as the trigger for considering adoption in most countries; however, the degree of alignment with WHO recommendations and duration of introduction processes vary. Endorsement by experts and availability of local evidence are leading criteria for adoption in upper-middle- and high income countries. Ease of administration, decreased pill burden, and reduced treatment costs are prioritized in low- and lower-middle-income settings. Countries report an average of 10 steps on the path to new treatment introduction, with core steps taking between 18 and 71 months. CONCLUSIONS: The process of new treatment introduction is complicated by diverse country processes, adoption criteria, and evidence requirements. Challenges differ between low- and middle-to-high-income countries. Responsiveness to the unique hurdles faced across settings is important in ensuring a sustainable market for improved pediatric anti-tuberculosis treatment. PMID- 26564539 TI - The journey to improve the prevention and management of childhood tuberculosis: the Kenyan experience. AB - Child tuberculosis (TB) cases in Kenya, a high TB burden country, constitute more than one tenth of all TB cases. This paper describes Kenya's efforts in the past decade to increase awareness about policy, improve leadership and combat the multiple challenges faced in the diagnosis and management of children presumed to have TB. We describe the increasing advocacy and involvement of paediatricians and the child health sector with the National TB Programme, and the resulting improvement in leadership, policy, child-specific guidelines and training materials, health worker capacity, and the implementation of prevention and cure of child TB. PMID- 26564540 TI - Treatment of childhood tuberculosis in India. AB - With a quarter of the global burden of tuberculosis (TB) occurring in India, children in this country are at high risk of tuberculous infection and TB disease. India's Revised National Tuberculosis Control Programme provides free diagnosis and treatment for children with TB using quality assured, weight-based individual drug boxes. Guidelines have recently been revised, updating both the diagnostic algorithm and shifting to a daily regimen with World Health Organization recommended dosages using child-friendly, fixed-dose combination pills. Active case finding is practised in households of TB patients as well as among human immunodeficiency virus infected and malnourished children. More attention needs to be paid to the provision of preventive therapy for household contacts aged <6 years as well as to the detection of multidrug-resistant TB among children. Case notification and the use of the Standards of TB Care in India are being strengthened in the private sector. PMID- 26564541 TI - Unmasking childhood tuberculosis in Pakistan: efforts to improve detection and management. AB - Childhood tuberculosis (TB) is getting increasing global attention, as tuberculous infection and TB disease in children indicate ongoing transmission in the community. In this note from the field, we highlight issues in child TB detection, management and prevention; child TB underdiagnosis, under-reporting and lack of integration with the National TB Programme are the main challenges faced in rural settings in Pakistan. We provide examples of solutions to overcome some of these challenges and enable early TB diagnosis, effective management and disease prevention in children. PMID- 26564542 TI - Childhood tuberculosis in the United States: shifting the focus to prevention. AB - In the last century, the United States has transitioned from a high to a low tuberculosis (TB) incidence country. A major factor in this decline has been the emphasis on identification and treatment of patients with tuberculous infection. While identification, testing, and preventive therapy pose challenges, recent developments in childhood TB offer more options for effective strategies that are acceptable to both children and their families. These include screening and testing in non-traditional settings, use of more specific assays (interferon gamma release assays) for testing, and implementation of shorter-course preventive regimens. PMID- 26564543 TI - Childhood tuberculosis: a unified response to a global problem. PMID- 26564544 TI - A bitter pill to swallow: the need for better medications for drug-resistant tuberculosis in children. AB - The large and growing access gap between the number of children who become sick with drug-resistant tuberculosis (DR-TB) and those who are treated for the disease each year represents a significant health systems failure. While there are multiple reasons why children with DR-TB are not diagnosed and treated, a serious challenge is the medications used to treat the disease. This paper presents three child DR-TB cases who were treated incorrectly; the cases are used to illustrate some of the problems with existing second-line medications. Challenges, including the perception that the drugs are more dangerous than the disease, lack of proper dosing recommendations and formulations, and the high cost of current treatment, all contribute to a perverse situation in which the most vulnerable pediatric patients are provided with a lower standard of care. This situation can be reversed with novel partnerships and training models, pharmacokinetic studies of the relevant drugs, increased collaboration, and dedicated funding, grounded in a rights-based approach to DR-TB in children. PMID- 26564545 TI - Paediatric formulations of second-line anti-tuberculosis medications: challenges and considerations. AB - There is a growing number of children worldwide accessing second-line anti tuberculosis drugs for multidrug-resistant tuberculosis (TB); however, there are very few child-friendly formulations. For paediatric use, dispersible tablets offer distinct advantages over liquid formulations and other approaches. This is particularly relevant for TB, where stability, long shelf-life and reduced manufacturing, transport and storage costs are all critical to ensuring that drugs are accessible and affordable. In addition, fixed-dose combinations that reduce the pill burden and provide adequate taste masking may promote long-term adherence to anti-tuberculosis treatment and prevention regimens likely to last many months in children. Partial adherence may result in treatment failure and the further selection and spread of resistant mycobacteria. Unfortunately, no second-line TB paediatric drugs exist in dispersible formulations. We discuss here the main obstacles to developing such tablets and present strategies for overcoming them. We also advocate for timely anticipation of paediatric use when new TB drugs are being developed, and for the development of child-friendly anti tuberculosis formulations in general. PMID- 26564546 TI - Accelerating clinical drug development for children with tuberculosis. AB - Despite urgent need, the development, approval and availability of child-friendly anti-tuberculosis drugs lag significantly behind that of adults, with children having been ignored in anti-tuberculosis drug development research. This paper outlines possible strategies for accelerating and better integrating the development of drugs and regimens for pediatric tuberculosis (TB) into existing drug development pathways for adults: initiation of pediatric studies of new treatments as soon as promising efficacy data have been generated in adults following successful phase II studies, shifting from the current age de-escalated approach to concomitant enrollment of children from the various age groups in studies, and leveraging the concepts of both the Unified Pathway and regimen development that have helped speed the study and development of novel regimens in adults. PMID- 26564547 TI - Acting on the call: bring childhood TB out of the shadows. PMID- 26564548 TI - Evaluation of oxidative and antioxidative parameters in generalized anxiety disorder. AB - Generalized anxiety disorder (GAD) is a prevalent psychiatric disorder. The exact causes of GAD still unknown, in addition to neurochemical and neuroanatomic disorders, genetic and environmental factors are discussed in etiology. In our study we aimed to evaluate the oxidative metabolism's status and investigate the role of oxidative metabolites in GAD. Blood samples were taken from enrolled subjects in appropriate way and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied in Harran University Biochemistry Labs. Results were compared between groups. The patients' TOS and OSI levels were significantly higher than control group. The patients' TAS levels were significantly lower than controls'. According to our findings, oxidative stress mechanism might have a role in GAD pathophysiology. In the future, total antioxidants may be used as a biologic marker in GAD etiology but more research is needed. PMID- 26564549 TI - Sexual risk behaviors among women with bipolar disorder. AB - The aim of this study was to investigate sexual health and sexual risk behaviors for sexually transmitted infections (STI) among women with bipolar disorder (BDW). Sixty-three euthymic women diagnosed with bipolar disorder type I, II or not otherwise specified were included and matched with a control group of 63 healthy women. Demographic and clinical data, structured sexual health measures and extensive assessment of sexual risk behavior were obtained and compared between groups. BDW had casual partners, were in non-monogamous sexual partnerships and had sex with partners with unknown HIV condition more frequently than healthy control women. History of two or more STI was more frequent among BDW. Inclusion of sexual behavior risk assessment among BDW in treatment is necessary to better identify those women with higher risk for STI and to take measures to improve their sexual health. PMID- 26564550 TI - Does cognitive impairment in treatment-resistant and ultra-treatment-resistant schizophrenia differ from that in treatment responders? AB - This study aimed to investigate whether cognitive impairment is more pronounced in people with treatment-resistant schizophrenia compared with those who respond well to first-line antipsychotic medication. Fifty-one patients with schizophrenia were assigned to one of three groups dependent on their clinical history: (i) 16 people who had responded well to first-line antipsychotic medication, (ii) 20 people who were treatment-resistant but responding to clozapine monotherapy, (iii) 15 people who were ultra-treatment resistant/clozapine-resistant but responding to antipsychotic polypharmacy. Twenty-two controls were also recruited. Groups were matched for age, sex, disease duration and psychopathology. All participants undertook a computerised battery of neuropsychological tests that assessed multiple cognitive domains. Raw data were converted to z-scores, and test performance was compared between groups. People with schizophrenia performed significantly worse than controls in the majority of neuropsychological tests, with verbal memory, sustained attention, and sensorimotor the most commonly impaired domains. No significant differences in performance between people deemed to be treatment-resistant or ultra-treatment-resistant, and those who responded well to first-line antipsychotic medication were observed. There was no significant relationship between antipsychotic dose and scores on any of the neuropsychological tests. Cognitive impairment is a central feature of schizophrenia, but our results suggest that treatment-resistance may not be associated with more severe deficits. PMID- 26564552 TI - Comparison of antioxidant activity of the fruits derived from in vitro propagated and traditionally cultivated tayberry plants. AB - BACKGROUND: Tayberry is a hybrid between Rubus fruticosus L. and Rubus idaeus L. These fruits contain valuable vitamins and antioxidants. An effective protocol for micropropagation of tayberry plants is here described. Different concentrations of cytokinins (6-benzylaminopurine, zeatin, and 6-(gamma,gamma dimethylallylamino)purine) were added in Murashige and Skoog, 1962 (MS) medium to micropropagation using stem tip and nodal explants. RESULTS: The highest propagation rate was recorded on MS medium containing 2 mg L(-1) zeatin, where the shoot formation resulted in 3.4 shoots per stem tip explant after 4 weeks of culture. It was found that half-strength MS medium with 0.1 mg L(-1) indole-3 butyric acid was the best for plant rooting. For ex vitro acclimatization of plants, the mixture of peat, soil, and perlite (1:1:1 v/v/v) was the most suitable planting substrate for hardening. The micropropagation protocol described in this study might be useful for the production of healthy plant materials. Tayberry fruits from in vitro propagated plants and adapted to the field conditions possessed higher antioxidant capacity in comparison to traditionally cultivated plants. CONCLUSION: Fruit extracts of micropropagated tayberry plants and adapted to field conditions can be used as a rich source of natural antioxidants. (c) 2015 Society of Chemical Industry. PMID- 26564553 TI - Highlights from the Faraday Discussion on Carbon Dioxide Utilisation, Sheffield, UK, September 2015. PMID- 26564551 TI - Cyclic di-AMP mediates biofilm formation. AB - Cyclic di-AMP (c-di-AMP) is an emerging second messenger in bacteria. It has been shown to play important roles in bacterial fitness and virulence. However, transduction of c-di-AMP signaling in bacteria and the role of c-di-AMP in biofilm formation are not well understood. The level of c-di-AMP is modulated by activity of di-adenylyl cyclase that produces c-di-AMP and phosphodiesterase (PDE) that degrades c-di-AMP. In this study, we determined that increased c-di AMP levels by deletion of the pdeA gene coding for a PDE promoted biofilm formation in Streptococcus mutans. Deletion of pdeA upregulated expression of gtfB, the gene coding for a major glucan producing enzyme. Inactivation of gtfB blocked the increased biofilm by the pdeA mutant. Two c-di-AMP binding proteins including CabPA (SMU_1562) and CabPB (SMU_1708) were identified. Interestingly, only CabPA deficiency inhibited both the increased biofilm formation and the upregulated expression of GtfB observed in the pdeA mutant. In addition, CabPA but not CabPB interacted with VicR, a known transcriptional factor that regulates expression of gtfB, suggesting that a signaling link between CabPA and GtfB through VicR. Increased biofilm by the pdeA deficiency also enhanced bacterial colonization of Drosophila in vivo. Taken together, our studies reveal a new role of c-di-AMP in mediating biofilm formation through a CabPA/VicR/GtfB signaling network in S. mutans. PMID- 26564554 TI - Estimating the number of cases of acute gastrointestinal illness (AGI) associated with Canadian municipal drinking water systems. AB - The estimated burden of endemic acute gastrointestinal illness (AGI) annually in Canada is 20.5 million cases. Approximately 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. A number of randomized controlled trials have been completed to estimate the influence of tap water from municipal drinking water plants on the burden of AGI. In Canada, 83% of the population (28 521 761 people) consumes tap water from municipal drinking water plants serving >1000 people. The drinking water-related AGI burden associated with the consumption of water from these systems in Canada is unknown. The objective of this research was to estimate the number of AGI cases attributable to consumption of drinking water from large municipal water supplies in Canada, using data from four household drinking water intervention trials. Canadian municipal water treatment systems were ranked into four categories based on source water type and quality, population size served, and treatment capability and barriers. The water treatment plants studied in the four household drinking water intervention trials were also ranked according to the aforementioned criteria, and the Canadian treatment plants were then scored against these criteria to develop four AGI risk groups. The proportion of illnesses attributed to distribution system events vs. source water quality/treatment failures was also estimated, to inform the focus of future intervention efforts. It is estimated that 334 966 cases (90% probability interval 183 006-501 026) of AGI per year are associated with the consumption of tap water from municipal systems that serve >1000 people in Canada. This study provides a framework for estimating the burden of waterborne illness at a national level and identifying existing knowledge gaps for future research and surveillance efforts, in Canada and abroad. PMID- 26564555 TI - Subclinical avian hepatitis E virus infection in layer flocks in the United States. AB - The objective of this study was to determine patterns of avian HEV infection in naturally infected chicken farms. A total of 310 serum samples and 62 pooled fecal samples were collected from 62 chicken flocks on seven commercial in-line egg farms in the Midwestern United States and tested for avian HEV circulation. Serum samples were tested for the presence of anti-avian HEV IgY antibodies by a fluorescent microbead immunoassay (FMIA) which was developed for this study. The FMIA was validated using archived samples of chickens with known exposure (n = 96) and compared to the results obtained with an enzyme-linked immunosorbent assay (ELISA) based on the same capture antigen. There was an overall substantial agreement between the two assays (kappa = 0.63) with earlier detection of positive chickens by the FMIA (P = 0.04). On the seven farms investigated, the overall prevalence of anti-avian HEV IgY antibodies in serum samples from commercial chickens was 44.8% (20-82% per farm). Fecal samples were tested for avian HEV RNA by a nested reverse-transcriptase PCR. The overall detection rate of avian HEV RNA in fecal samples was 62.9% (0-100% per farm). Sequencing analyses of partial helicase and capsid genes showed that different avian HEV genotype 2 strains were circulating within a farm. However, no correlation was found between avian HEV RNA detection and egg production, egg weight or mortality. In conclusion, avian HEV infection is widespread among clinically healthy laying hens in the United States. PMID- 26564556 TI - The physical activity patterns of adolescents with intellectual disabilities: A descriptive study. AB - BACKGROUND: Emerging data suggest that adolescents with intellectual disabilities (IDs) have lower physical activity (PA) levels and have a higher incidence of obesity than their peers without IDs. OBJECTIVE: To examine daily PA patterns (weekdays vs. weekend days) of adolescents with IDs among boys and girls. The contributions of PA at school, including school recesses and physical education time, and PA outside of school were also analyzed. METHODS: Participants included forty-nine adolescents with mild to moderate IDs (mean 15.3 years) from the Valencia region (Spain). Adolescents wore a pedometer for seven consecutive days to measure PA objectively and filled in a daily activity log. Mean steps for weekdays, weekend days, and for the different day segments were calculated and compared. RESULTS: This study indicates significant differences in daily PA levels between boys and girls (12,630 and 9599 steps respectively; p < 0.05). Girls were less active than boys on weekdays (13,872 vs. 9868 steps; p = 0.016), during school time (7097 vs. 4802 steps; p = 0.005), and during school recesses (1953 vs. 1147 steps; p = 0.033). Boys showed higher levels of PA on weekdays compared to weekend days (13,872 vs. 10,188 steps; p = 0.015) and PA at school represented 50% of the participants' daily PA in both genders. There were no differences comparing weight status groups (normal vs. overweight/obese) in PA levels either on weekdays or weekend days. CONCLUSIONS: These findings provide an empirical basis for interventions to increase PA levels among adolescents with IDs. PMID- 26564557 TI - Financial burdens and barriers to care among nonelderly adults: The role of functional limitations and chronic conditions. AB - BACKGROUND: People with functional limitations and chronic conditions account for the greatest resource use within the health care system. OBJECTIVE: To examine financial burdens and barriers to care among nonelderly adults, focusing on the role of functional limitations and chronic conditions. METHODS: High financial burden is defined as medical spending exceeding 20 percent of family income. Financial barriers are defined as delaying care/being unable to get care for financial reasons, and reporting that delaying care/going without was a big problem. Data are from the Medical Expenditure Panel Survey (2008-2012). RESULTS: Functional limitations are associated with increased prevalence of financial burdens. Among single adults, the frequency of high burdens is 20.3% for those with functional limitations, versus 7.8% for those without. Among those with functional limitations, those with 3 or more chronic conditions are twice as likely to have high burdens compared to those without chronic conditions (22.2% versus 11.1%, respectively). Similar patterns occur among persons in multi-person families whose members have functional limitations and chronic conditions. Having functional limitations and chronic conditions is also strongly associated with financial barriers to care: 40.2% among the uninsured, 21.9% among those with public coverage, and 13.6% among those with private group insurance were unable to get care. CONCLUSIONS: Functional limitations and chronic conditions are associated with increased prevalence of burdens and financial barriers in all insurance categories, with the exception that an association between functional limitations and the prevalence of burdens was not observed for public coverage. PMID- 26564559 TI - [Current status in rehabilitation of burn injury in China]. AB - Along with the advance in national economy, modern concept of burn rehabilitation from major burn injury implies that measures should be taken to help the patients return to society with dignity. This article briefly reviews the development and achievement of burn rehabilitation in our country, as well as the current difficulties in carrying out rehabilitation measures such as outmoded ideology, lack of trained personnel, low rat of popularization, outdated techniques and methodology, and relatively low level in scientific research, etc. The future development of burn rehabilitation in our country needs more social support, popular attention, and multidisciplinary joint efforts to help burn patients return to society with dignity. In order to fulfill this goal, we still have a long way to go. PMID- 26564558 TI - Somatic copy number losses on chromosome 9q21.33q22.33 encompassing the PTCH1 loci associated with cardiac fibroma. AB - Cardiac fibroma is an extremely rare benign tumor that remains poorly characterized genetically. Somatic copy number alterations are common in tumors and have been defined as a crucial factor leading to tumors. In this study, we present a child diagnosed with cardiac fibroma with somatic copy number losses of a total of three discontinuous segments from 9q21.33 to 9q22.33, including a mosaic deletion of PTCH1. PTCH1 has been associated with sporadic cardiac fibroma. Sequencing analysis of the PTCH1 gene has not revealed any causative mutation. Quantitative PCR analysis of PTCH1 further confirms somatic copy number losses. Our data narrow down the critical causative deletions for sporadic cardiac fibroma to a region more precise than any other previously reported one. Our results suggest important roles of somatic copy number losses on chromosome 9q21.33q22.33 in the development of sporadic cardiac fibroma; these findings may provide a better understanding of sporadic cardiac fibroma pathogenesis and contribute to the identification of novel diagnostic biomarkers of this neoplasm. . PMID- 26564560 TI - [Clnical observation, of the effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine on the treatment of hyperplastic scar]. AB - OBJECTIVE: To explore the clinical effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine ( Fuchunsan ) on the treatment of postburn hyperplastic scar. METHODS: Sixty-three patients with hyperplastic scar after burn injury hospitalized from February 2012 to June 2014 in our department were treated with lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan). Patients were divided into early stage group (E, n = 35), middle stage group (M, n = 25), and late stage group ( L, n = 3) according to the formation time of scar, which was respectively 3 weeks to 3 months, longer than 3 months and less than or equal to 6 months, and 3 to 15 years in groups E, M, and L. The number of times of laser treatment of patients in each group was recorded. The degree of scar pain in patients of the three groups was assessed by the Numerical Rating Scale (NRS) before treatment and after treatment for 1, 2, and 3 times. The scar condition of patients in groups E and M was assessed by the Vancouver Scar Scale (VSS) before treatment and after treatment for 1, 3, and 5 times. Patients in group L did not receive VSS assessment but were evaluated by clinical observation only. Photos of scar in treating area were taken before treatment and after treatment for 3 and 5 times to evaluate the clinical effect. Data were processed with t test. RESULTS: Patients in groups E and M were treated with laser for (4.8 +/- 1.1) and (7.7 +/- 2.1) times respectively. In group L, the treatment was stopped in 2 patients after laser treatment for 5 times, and 1 patient received laser treatment for 12 times. The degree of pain in patients of groups E and M was alleviated significantly after treatment for one time, and the number of patients scoring 1 4 point(s) in NRS increased from 5 cases to 38 cases. After treatment for 2 and 3 times, the increase in the number of patients scoring 1-4 point (s) in NRS was on a small scale. Before treatment and after treatment for 1 time, VSS scores of patients in groups E and M were similar (with values respectively 0.641 and 0. 082, P values above 0. 05). After treatment for 3 and 5 times, VSS scores of patients in group E were respectively (9.2 +/- 0.8) and (7.0 +/- 1.1) points, which were significantly lower than those in group M [ (9.7 +/- 1.0) and (8.2 +/- 1.0) points, with values respectively -1.993 and -4.433 , P < 0.05 or P < 0.01]. After treatment for 3 times, the rate of improvement in appearance was respectively 88.6% (31/35) and 72.0% (18/25) in groups E and M, and it was respectively 100.0% (35/35) and 96.0% (24/25) after treatment for 5 times. No significant effect in appearance was found in the 3 patients in group L. CONCLUSIONS: Early application of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan) for the treatment of postburn hyperplastic scar is effective. PMID- 26564561 TI - [Bibliometric analysis of scientific articles on rehabilitation nursing for adult burn patients in China]. AB - OBJECTIVE: To analyze the current research status of rehabilitation nursing for adult burn patients in China, and to disuss the related strategies. METHODS: Chinese scientific articles on adult burn patients' rehabilitation nursing published from January 2003 to December 2013 were retrieved from 3 databases namely China Biology Medicine disc, Chinese Journals Full-text Database , and Chinese Science and Technology Journals Database . From the results retrieved, data with regard to publication year, journal distribution, research type, region of affiliation of the first author, and the main research content were collected. Data were processed with Microsoft Excel software. RESULTS: A total of 417 articles conforming with the criteria were retrieved. During the 11 years, the number of the relevant articles per year was on the rise, and the increasing rates in 2005, 2008, 2009, and 2013 were all above 30% . Regarding the distribution among journals, these 417 articles were published in 151 journals, with 188 articles in Source Journal for Chinese Scientific and Technical Papers , accounting for 45.08%. Regarding the research type, 173 out of the 417 articles were dealing with clinical experiences, accounting for 41.49% ; 172 out of the 417 articles were dealing with experimental studies, accounting for 41.25% . The regions of affiliation of the first author were mainly situated in Guangdong province, Shandong province, Hunan province, and Jiangsu province, with Guangdong province contributing 58 articles, accounting for 13.91%. The research content of these articles was mainly focused on psychological nursing, nursing model, and health education, respectively 188,101, and 85 articles, accounting for 45.08%, 24.22%, and 20.38%. CONCLUSIONS: The research on rehabilitation nursing for adult burn patients in China has been carried out nationwide. Although the number of relevant papers is on the rise, the quality of these papers needs to be further improved. There is an urgent need for the guideline on rehabilitation nursing for adult burn patients in China so as to standardize the content and procedure of rehabilitation nursing. PMID- 26564562 TI - [Retrospective analysis of effects of metacarpus and phalanx traction on correction of scar contracture of hand after burn on the palm side]. AB - OBJECTIVE: To analyze the effects of metacarpus and phalanx traction on correction of scar contracture of hand after burn on the palm side retrospectively. METHODS: A total of 32 patients with 39 affected hands with scar contracture on the palm side after burn were hospitalized from May 2010 to December 2014. Method of treatment: scar contracture was conservatively released followed by skin grafting, which was referred to as method A; Kirschner wire was inserted into the middle or distal phalanx of finger with contracture and the corresponding metacarpus in the shape of U for 2 to 7 weeks' traction, which was referred to as method B; traction frame was built based on the traction pile and anchor formed by Kirschner wire inserted through the second to the fifth metacarpus and distal phalanx of finger with contracture, and then the affected fingers were pulled into a straight position with rubber bands for 2 to 6 months, which was referred to as method C. Method A was used in patients who would be treated with thorough release of scar followed by skin grafting routinely. Method B was used in patients who would be treated with intramedullary Kirschner wire fixation after release of scar contracture and skin transplantation routinely. Method C was further used in patients when methods A and B failed to accomplish the expected result. Method C was used in the first place followed by method A in whom there might be vascular decompensation or exposure of tendon and bone after scar release, and those who failed to meet the expectation were treated with method C in addition. Patients who were unwilling to undergo surgery were treated with method C exclusively. During the course of treatment, the presence or absence of infection and slipping of Kirschner wire or its slitting through soft tissue were observed. The presence or absence of tendency of recurrence of scar contracture within 1 to 2 weeks after treatment was observed. The length of palmar skin measuring from the root of finger with contracture to wrist crease was measured before treatment, at the termination of treatment, and 1 month after the termination of treatment. Scar condition was assessed with the Vancouver Scar Scale (VSS) before treatment and 1, 3, and 6 month(s) after the termination of treatment. Before treatment and 1 month after the termination of treatment, the range of motion was measured with the Total Active Movement (TAM) method; band function was evaluated by the Jebsen Test of Hand Function (JTHF), and the completion time was recorded. Data were processed with analysis of variance, LSD t test, and t test. RESULTS: Twenty-four patients with 27 affected hands were treated with scheme A + B; 5 patients with 7 affected hands were treated with method C exclusively; 2 patients with 3 affected hands were treated with scheme A + B + C; 1 patient with 2 affected hands were treated with scheme C + A + C. During the course of treatment, no complication such as infection or slicing of tissue was observed, but there was a slight shifting of U-shaped Kirschner wire in 14 affected hands of 13 patients. Tendency of recurrence of scar contracture was observed in 11 affected hands of 10 patients, but the scar contracture did not reoccur after treatment with orthosis. The skin length of palmar side was respectively (131.8 +/- 9.8) and (127.6 +/- 7.5) mm at the termination of treatment and 1 month after, and they were both significantly longer than that before treatment [(114.5 +/- 2.4) mm, with values respectively 10.71 and 10.39, P values below 0.001]. The score of VSS was respectively (9.8 +/- 2.4), (9.7 +/- 1.7), (9.3 +/- 0.8), and (7.7 +/- 0.5) points before treatment and 1, 3, and 6 month(s) after the termination of treatment. Only the score at 6 months after the termination of treatment was significantly lower than that before treatment (t = 3.28, P < 0.01). The ratio of excellent and good results according to method TAM was respectively 2.6% (1/39) and 94.9% (37/39) before treatment and 1 month after the termination of treatment. The time for JTHF measurement was (13.9 +/- 4.1) min before treatment, and it was shortened to (11.0 +/- 2.8) min 1 month after the termination of treatment (t = 3.65, P < 0.001). CONCLUSIONS: Single application of metacarpus and phalanx traction or its combination with skin transplantation after scar release in correcting scar contracture of the palm of hand after burn can lengthen the contracted tissue, and it is beneficial for the restoration of function and appearance of affected hand. PMID- 26564563 TI - [Clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn]. AB - OBJECTIVE: To study the clinical effects of gabapentin on the treatment of pruritus of scar resulting from deep partial-thickness burn. METHODS: A total of fifty-eight patients suffering from pruritus of scar after deep partial-thickness burn were hospitalized from January 2013 to January 2014. Patients were divided into placebo group (n =18, treated with oral vitamin C in the dose of 100 mg for 4 weeks, twice per day) , cetirizine group (n = 20, treated with oral cetirizine in the dose of 10 mg for 4 weeks, twice per day) , and gabapentin group (n = 20, treated with oral gabapentin in the dose of 300 mg for 4 weeks, twice per day) . Before treatment and on post treatment day (PTD) 3 and 28, the Visual Analog Scale (VAS) was used to assess the itching degree, and the mean scores were recorded. The remission rates of pruritus on PTD 3 and 28 were calculated. The adverse effects were observed during treatment. Data were processed with analysis of variance, q test, and chi-square test. RESULTS: Compared with that before treatment, the itching degree of patients with light, moderate, and severe itching in placebo group was not relieved after treatment; the itching degree of patients with moderate or severe itching in cetirizine group was alleviated after treatment, but not in patients with light itching; itching degree of all patients in gabapentin group was significantly relieved after treatment. There were no obvious differences in VAS scores among the 3 groups before treatment (F = 2.78, P > 0.05). On PTD 3 and 28, the VAS scores of patients in both gabapentin group [(2.3 +/- 0.8) and (0.6 +/- 0.3) points] and cetirizine group [(4.2 +/- 1.7) and (2.8 +/- 1.2) points] were lower than those in placebo group [(5.7 +/- 2.0) and (5.7 +/- 1.9) points, with q values from 6.70 to 7.75, P values below 0.05]. The VAS scores of patients in gabapentin group on PTD 3 and 28 were lower than those in cetirizine group (with q values respectively 6.30 and 6.90, P values below 0.05). The remission rates of pruritus of patients in gabapentin group on PTD 3 and 28 were respectively (66 +/- 20)% and (91 +/- 17)%, and they were higher than those in cetirizine group [(33 +/- 8)% and (56 +/- 14)%, with q values respectively 4.70 and 3.82, P values below 0.05]. The remission rate of pruritus of patients in placebo group on PTD 3 and 28 was 0, which was lower than that of the other 2 groups each (with q values from 3.94 to 6.76, P values below 0.05). During the course of treatment, 5 patients in gabapentin group suffered from adverse effects including mild-to-moderate drowsiness and dizziness, but they disappeared one week later. No adverse effects were observed in patients of the other two groups. CONCLUSIONS: For patients with deep partial-thickness burn, gabapentin can effectively alleviate scar itching after wound healing with safety. PMID- 26564564 TI - [Advances in the research of effects of music therapy on pain and anxiety in burn patients]. AB - Pain and anxiety engender major psychic problems during all phases of treatment for burn patients. Analgesic alone does not allay these problems satisfactorily in these patients. Music therapy, as an important complementary and alternative therapy, has been widely used in multiple medical fields. However, its positive effect on alleviation of pain and anxiety in burn patients is undefined. The objective of this review is to summarize the feasibility, application fields, methods, and the effectiveness of music therapy in allaying pain and anxiety of burn patients during the whole course of treatment. PMID- 26564565 TI - [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema]. AB - OBJECTIVE: To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. METHODS: The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. RESULTS: There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 +/- 3.1) and (12.1 +/- 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 +/- 0.5 and (2.1 +/- 0.6) points, and they were significantly higher than those in group H [1.4 +/- 0.3 and (1.0 +/- 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 +/- 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 +/- 168) mL/m2 and (212 +/- 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and there was obviously negative correlation between oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.674 and -0.817, P values below 0.01). In group H, there was obviously positive correlation between EVLWI and ITBVI (r = 0.751, P < 0.01) but no obvious correlation between EVLWI and PVPI, oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively 0.275, 0.197, and 0:062, P values above 0.05). The total area under ROC curve of PVPI value for differentiating the type of pulmonary edema was 0.987 [with 95% confidence interval (CI) 0.962-1.013, P < 0.01], and 1.9 was the cutoff value with sensitivity of 94.1% and specificity of 95.2% . The total area under ROC curve of ITBVI value for differentiating the type of pulmonary edema was 0.940 (with 95% CI 0.860-1.020, P < 0.01), and 1,077. 5 mL/m2 was the cutoff value with sensitivity of 95.2% and specificity of 88.2%. CONCLUSIONS: EVLWI, PVPI, and ITBVI have an important significance in the differential diagnosis of the type of burn-induced pulmonary edema, and they may be helpful in the early diagnosis and management of burn-induced pulmonary edema. PMID- 26564566 TI - [Effects of microtubule depolymerization on spontaneous beating and action potential of cardiac myocytes in rats and its mechanism]. AB - OBJECTIVE: To explore the effects of microtubule depolymerization (MD) on the spontaneous beating rate, action potential (AP), and oxygen consumption of cardiac myocytes in rats and its mechanism. METHODS: One-hundred and eighty neonatal SD rats divided into 12 batches were used in the experiment, and 15 rats in each batch were sacrificed for the isolation and culture of cardiac myocytes after the heart tissues were harvested. The cardiac myocytes were respectively inoculated in one 12-well plate filled with 6 round cover slips, one 12-well plate filled with 6 square cover slips, two cell culture flasks, and two cell culture dishes. After routine culture for three days, the cardiac myocytes from all the containers were divided into normal control group (NC, routinely cultured with 3 mL DMEM/F12 solution rewarmed at 37 degrees C for 3 h) and group MD (routinely cultured with 3 mL DMEM/F12 solution rewarmed at 37 degrees and containing 8 umol/L colchicine for 3 h) according to the random number table, with 3 holes, 1 flask, or 1 dish in each group. The morphological changes in microtubules were observed with confocal laser scanning microscope after immunofluorescent staining. The content of polymerized or dissociative alpha tubulin was determined by Western blotting. Spontaneous beating rate of the cells was observed and calculated under inverted microscope. Dissolved oxygen concentration of DMEM/F12 solution containing cardiac myocytes was determined by oxygen microelectrode system before and after the addition of colchicine. Additionally, dissolved oxygen concentration of DMEM/F12 solution and colchicine + DMEM/F12 solution was determined. The whole-cell patch-clamp technique was used to record AP, delayed rectifier K+ current (I(K)), and L-type Ca2+ current (I(Ca L)) in cardiac myocytes; current density-voltage (I-V) curves were drawn based on the traces. Data were processed with independent or paired samples t-test. RESULTS: (1) In group NC, microtubules of cardiac myocytes were around the nucleus in radial distribution with intact and clear linear tubiform structure. The microtubules in group MD were observed in dispersive distribution with damaged structure and rough linear tubiform structure. (2) In group MD, the content of dissociative alpha-tubulin of cells (0.61 +/- 0.03) was obviously higher than that in group NC (0.46 +/- 0.03, t = -6.99, P < 0.05), while the content of polymerized alpha-tubulin (0.57 +/- 0.04) was significantly lower than that in group NC (0.88 +/- 0.04, t = 9.09, P < 0.05). (3) Spontaneous beating rate of cells was (59 +/- 8) times per min in group MD, which was distinctly higher than that in group NC [(41 +/- 7) times per min, t = 5.62, P < 0.01]. (4) Dissolved oxygen concentration of DMEM/F12 solution containing cardiac myocytes was (138.4 +/- 2.5) umol/L, and it was reduced to (121.7 +/- 3.6) umol/L after the addition of colchicine ( t = 26.31, P < 0.05). There was no obvious difference in dissolved oxygen concentration between DMEM/F12 solution and colchicine + DMEM/F12 solution (t = 0.72, P > 0.05). (5) Compared with that of group NC, AP morphology of cells in group MD changed significantly, with unobvious repolarization plateau phase and shorter action potential duration (APD). The APD20, APD50, and APD90 were respectively (36.2 +/- 3.8), (73.7 +/- 5.7), and (115.1 +/- 8.0) ms in group MD, which were significantly shorter than those of group NC [(40.2 +/- 2.3), (121.4 +/- 7.0), and (169.4 +/- 5.6) ms, with t values respectively 2.61, 15.88, and 16.75, P values below 0.05]. (6) Compared with that of group NC, the I-V curve of I(K) of cells in group MD moved up with higher current density under each test voltage (0 to 40 mV) after activation ( with t values from 2. 70 to 3. 76, P values below 0.05) . (7) There was not much alteration in current density of I(Ca-L) under each test voltage (-30 to 50 mV) between 2 groups (with t values from -1.57 to 1.66, P values above 0.05), and their I-V curves were nearly overlapped. CONCLUSIONS: After MD, the I(K) is enhanced without obvious change in I(Ca-L), making AP repolarization faster and APD shortened. Then the rapid spontaneous beating rate increases oxygen consumption of cardiac myocytes of rats. PMID- 26564567 TI - [Effects of adipose-derived mesenchymal stem cells over-expressing glial cell line-derived neurotrophic factor on electrically injured sciatic nerve of rats]. AB - OBJECTIVE: To observe the effects of adipose-derived mesenchymal stem cells (ADSCs) with continous over-expression of glial cell line-derived neurotrophic factor (GDNF) on the motor function recovery and nerve regeneration of sciatic nerve of rats after electrical injury. METHODS: Five SD rats were collected to prepare ADSCs with over-expression of GDNF. One hundred and fifty SD rats were divided into normal control group (N), GDNF-ADSCs group (GA), ADSCs group (A), GDNF group (G), and physiological saline group (P) according to the random number table, with 30 rats in each group. Rats in group N were routinely fed without treatment, and rats in the other 4 groups were inflicted with electrical injury on sciatic nerve of thigh of the right hind leg. Rats in groups GA, A, G, and P were respectively injected with 100 uL suspension of ADSCs with over-expression of GDNF (1 x 10(7) cells per mL), 100 [uL ADSCs suspension (1 x 10(7) cells per mL), 100 uL GDNF solution (100 mg/L) , and 100 uL physiological saline to the surface of the injured nerves immediately after injury. Six rats of each group were collected for measuring hind limb stride from post injury week (PIW) 1 to 8, and morphology of the sciatic nerves was observed in PIW 8. In PIW 4, the protein expression of GDNF of sciatic nerves of the rest rats in each group was determined with Western blotting. Data were processed with one-way analysis of variance, analysis of variance of repeated measurement, and SNK test. RESULTS: Compared with that of group N, the hind limb stride values in groups GA, A, G, and P were significantly lower at each time point (with P values below 0.05). Compared with those of group P, the hind limb stride values in group GA from PIW 3 to 8, in group A in PIW 3, 5, and 7, and in group G in PIW 3, 5, 7, and 8 were significantly longer (with P values below 0.05). The hind limb stride values in group GA from PIW 4 to 8 were respectively (10.83 +/- 0.97), (13.25 +/- 1.40), (12.86 +/- 1.42), (14.06 +/- 1.50), and (15.09 +/- 1.17) cm, which were significantly longer than those in group A [(8.90 +/- 0.82), (9.03 +/- 0.57), (9.27 +/- 0.36), (9.86 +/- 0.36), and (9.52 +/- 0.58) cm] and group G [(8.87 +/- 0.69), (8.51 +/- 1.18), (9.34 +/- 0.87), (9.76 +/- 0.67), and (9.50 +/- 1.22) cm], with P values below 0.05. Compared with that of group N, the number of myelinated nerve fibers of sciatic nerves was obviously decreased in group P but obviously increased in groups GA, A, and G; the diameter of axons was obviously shorter, and the myelin thickness was obviously increased in groups GA, A, G, and P in PIW 8 (with P values below 0.05). The number of myelinated nerve fibers in group GA was 31.2 +/- 0.8, which was significantly higher than that in group A (23.7 +/- 2.7), group G (22.3 +/- 2.7), or group P (9.3 +/- 2.8), with P values below 0.05. The diameter values of axons among groups P, A, G, and GA were similar (with P values above 0.05). The myelin thickness of rats in group GA was (3.41 +/- 0.34) um, which was significantly thicker than that in group A [(2.64 +/- 0.37) um] or group G [(2.41 +/- 0.34) um], with P values below 0.05. In PIW 4, the protein expression of GDNF of sciatic nerves was significantly higher in groups P, A, G, and GA than in group N (with P values below 0.05), and the protein expression of GDNF in group GA was significantly higher than that in group P, A, or G (with P values below 0.05). CONCLUSIONS: ADSCs over-expressing GDNF protein can obviously promote the motor function recovery and nerve regeneration of sciatic nerve of rats after electrical injury. PMID- 26564569 TI - [Effects of resuscitation with different kinds of colloids on oxygen metabolism in swine during shock stage of burn injury]. AB - OBJECTIVE: To explore the effects of resuscitation with different kinds of colloids on oxygen metabolism of swine during shock stage of burn injury. METHODS: Eighteen Guangxi Bama miniature swine were inflicted with 40% TBSA full thickness burn on the back. And then they were divided into succinylated gelatin group (S) , hydroxyethyl starch group (H), and allogeneic plasma group (A) according to the random number table, with 6 swine in each group. The fluid resuscitation was begun at post injury hour (PIH) 2. The colloids used in groups S, H, and A were respectively succinylated gelatin, 60 g/L hydroxyethyl starch 130/0.4, and allogeneic plasma. The blood pressure, urine volume, heart rate, and central venous pressure (CVP) were recorded before injury and at the first and second PIH 24. The volume of resuscitation fluid was recorded at the first and second PIH 24. The changes in oxygen delivery., oxygen consumption, oxygen extraction ratio and D-lactate were determined and calculated before injury and at PIH 4, 8, 24, and 48. Data were processed with analysis of variance of repeated measurement, one-way analysis of variance and LSD test. RESULTS: There were no statistically significant differences among the three groups in blood pressure, urine volume, heart rate, and CVP at each time point (with P values above 0. 05). There were no statistically significant differences in resuscitation fluid volume among the three groups at the first and second PIH 24 (with F values respectively 0. 239 and 2. 023, P values respectively 0. 790 and 0. 167). The oxygen consumption of swine in group S was (201 +/- 38) L . min(-1) . m(-2) at PIH 48, which was significantly higher than that in group A [(150 +/- 37) L . min(-1) . m(-2), P < 0.05], and the oxygen consumption was similar among the three groups at the rest time points (with P values above 0.05). The oxygen delivery of swine in group S was (484 +/- 63) L . min(-1) . m(-2) at PIH 8, and it was significantly lower than that in group A [(652 +/- 65) L(-1) min(-1) . m( 2), P < 0.01]. The oxygen delivery of swine in group S reached (903 +/- 132) and (1,028 +/- 98) L . min(-1) . m(-2) at PIH 24 and 48, respectively, and they were significantly higher than those in group A [(686 +/- 72) and (720 +/- 75) L . min(-1) . M(-2), with P values below 0.01]. Oxygen delivery in group H was similar to that of group A at each time point (with P values above 0.05). The oxygen extraction ratio in group S or group H was close to that of group A at each time point (with P values above 0.05). The D-lactate level in group S was (69 +/- 9) mmol/L, and it was significantly higher than that in group A [(52 +/- 4) mmol/L, P < 0.01] at PIH 48. The D-lactate level was similar among the three groups at the rest time points (with P values above 0.05). CONCLUSIONS: According to the changes in oxygen metabolism of swine during shock stage of burn injury resuscitated with different kinds of colloids, it is found that allogeneic plasma is better than artificial colloid, and 60 g/L hydroxyethyl starch 130/0.4 is superior to succinylated gelatin. PMID- 26564568 TI - [Analysis of the mechanism of drug resistance of VIM-2-type metallo-beta lactamase-producing Acineto- bacter baumannii isolated from burn patients and its homology]. AB - OBJECTIVE: To study the drug resistance of Acinetobacter baumannii (AB) producing VIM-2-type metallo-beta-lactamase (MBL) isolated from burn patients of our ward against carbapenem antibiotics and its homology. METHODS: A total of 400 strains of AB (identified) were isolated from sputum, urine, blood, pus, and wound drainage. of burn patients hospitalized in our ward from September 2011 to March 2014. Drug resistance of the 400 strains of AB to 15 antibiotics, including compound sulfamothoxazole, aztreonam, etc. , was tested using the automatic microorganism identifying and drug sensitivity analyzer. Among the carbapenems resistant AB isolates, modified Hodge test was applied to screen carbapenemase producing strains. The carbapenemase genes of the carbapenemase-producing strains, and the mobile genetic elements class I-integron (Intl1) gene and conserved sequence (CS) of carbapenemase-producing strains carrying blaVIM-2 gene were determined with PCR and DNA sequencing. For carbapenemase-producing strains carrying blaVIM-2 gene, synergism test with imipenem-ethylene diamine tetraacetic acid (EDTA) and enhancement test with imipenem-EDTA and ceftazidime-EDTA were used to verify the MBL-producing status. Drug resistance of the VIM-2-type MBL producing AB strains was analyzed. For VIM-2-type MBL-producing AB strains, plasmid conjugation experiment was used to explore the transfer of plasmid; outer membrane protein (OMP) CarO gene was detected by PCR. For VIM-2-type MBL producing AB strains carrying CarO gene, the protein content of CarO was analyzed with sodium dodecyl sulfate polyacrylamide gel electro- phoresis. The repetitive consensus sequence of Enterobacteriaceae genome PCR (ERIC-PCR) was carried out for gene typing of VIM-2-type MBL-producing AB strains to analyze their homology. RESULTS: (1) The resistant rates of the 400 strains of AB against levofloxacin and compound sulfamethoxazole were low. A total of 381 carbapenems-resistant AB strains were screened, including 240 carbepenemase-producing strains. (2) Out of the 240 carbepenemase-producing strains, 18 strains were found to harbor the blaVIM-2 gene, accounting for 7.5%; 133 strains carried the blaTEM-1 gene, accounting for 55.42%; 195 strains carried the blaOXA23 gene, accounting for 81.25%; 188 strains carried the bla(armA) gene, accounting for 78.33%. (3) Eighteen carbepenemase-producing strains which carried the bla(VIM-2) gene were found to carry the Intl1 gene, showing the Intl1-VIM linkage. Simultaneously, Intl1 variable area CS showed diversity. (4) Eighteen carbepenemase-producing strains which carried the blaVIM-2 gene were verified to produce MBL. The resistant rates of the 18 strains of AB against compound sulfamethoxazole were the lowest, followed by levofloxacin and cefoperazone/sulbactam, and those against the other antibiotics were above 60.00%. (5) Through multiple joint tests, plasmid conjugation experiment positive transfer strain was not found in 18 VIM-2-type MBL-producing AB strains. (6) Nine out of the 18 VIM-2-type MBL producing AB strains were found to carry CarO gene. The OMP CarO of VIM-2-type MBL-producing AB strains carrying CarO gene was lost or lowered in the protein content. (7) The 18 VIM-2-type MBL-producing AB strains were classified into 6 genotypes by the ERIC-PCR. There were respectively 6, 4, 3, and 1 stain (s) in genotypes A, B, C, and F, and there were 2 strains in genotypes D and E respectively. CONCLUSIONS: The resistance mechanism of AB against carbapenems is mainly mediated by blaTEM-1, blaOXA-23, and bla(arma); meanwhile, VIM-2-type MBL producing and lack or change in OMP CarO are attributable to carbapenems resistance of clinically isolated AB from burn wards, and the Intl1 gene may take a part in blaVIM-2 gene transmission. PMID- 26564570 TI - [Advances in the research of early systemic use of prophylactic antibiotics in severe burns]. AB - Infection is the most common complication and the most common cause of death in burn patients. It is very important to employ anti-infection measures reasonably and effectively for victims of major burns. However, a consensus of opinion of how to use systemic antibiotics in prophylaxis of infection in the early stage of burn is still lacking. The indications of the early systemic use of prophylactic antibiotics are discussed in this article. PMID- 26564571 TI - [Current situation of research and application of Parkland formula in burn resuscitation]. AB - Parkland formula is the most widely used resuscitation formula in burn care. However, a growing number of disputes have been raised along with the development of medical technology, among which its total volume and composition of the fluid are the two foci. Firstly, Parkland formula may lead to an untoward phenomenon nicknamed "fluid creep", which may lead to complications such as abdominal compartment syndrome. Secondly, along with the deeper understanding of how permeability of blood vessels changes after burn injury, colloid is recommended to be given after the third 8 h post-burn. Additionally, controversy exists in the choice of different colloid solutions. The safety of different colloid solutions remains to be further elucidated. This article will deal with all of the above-mentioned problems. PMID- 26564572 TI - [Advances in the experimental study of the use of mesenchy- mal stem cells for the treatment of inhalation injury]. AB - Inhalation injury seriously threatens the survival and quality of life in burn and trauma patients. So far there is no breakthrough in the treatment of inhalation injury. A significant advance has been witnessed in the experimental study of the use of stem cells in the treatment of lung injury in recent years. In this paper, according to the results of our study in the systemic transplantation of bone marrow mesenchymal stem cells for the treatment of inhalation injury, the effect of mesenchymal stem cells on anti-inflammatory process and repair of lung tissues in inhalation injury, and its possible mechanisms are reviewed. PMID- 26564573 TI - Determination of nifurtimox in dog plasma by stable-isotope dilution LC-MS/MS. AB - BACKGROUND: Nifurtimox is a 5-nitrofuran derived antiprotozoal drug used to treat diseases caused by trypanosomes including Chagas' disease and sleeping sickness (African trypanosomiasis). Available methods for the determination of nifurtimox in plasma are tedious and of low sensitivity. For the first time, an isotope dilution HPLC/MS/MS method for the sensitive quantitation of nifurtimox down to 10.0 MUg/l in plasma is described. RESULTS: Protein precipitation was used for sample preparation. Samples were analyzed on a standard triple quadrupole tandem mass spectrometer. The validated concentration range covers 10.0 MUg/l (LLOQ) to 5000 MUg/l. Interassay accuracy and precision (%CV) ranged from 98.4 to 101%, and 2.61 to 10.1%, respectively. CONCLUSION: The method consists of very simple sample preparation and provides unmatched sensitivity, high reproducibility and robustness enabling analysis of large sample numbers. Method performance met current guidelines on bioanalytical method validation. PMID- 26564575 TI - Pain trajectory and exercise-induced pain flares during 8 weeks of neuromuscular exercise in individuals with knee and hip pain. AB - OBJECTIVE: Patients considering or engaged in exercise as treatment may expect or experience transient increases in joint pain, causing fear of exercise and influencing compliance. This study investigated the pain trajectory during an 8 week neuromuscular exercise (NEMEX) program together with acute exercise-induced pain flares in persons with knee or hip pain. DESIGN: Individuals above 35 years self-reporting persistent knee or hip pain for the past 3 months were offered 8 weeks of supervised NEMEX, performed in groups twice weekly. The program consisted of 11 exercises focusing on joint stability and neuromuscular control. Participants self-reported joint pain on a 0-10 numerical rating scale (NRS) at baseline and 8-weeks follow-up. NRS pain ratings were also collected before and immediately after every attended exercise session. RESULTS: Joint pain was reduced from baseline (NRS 3.6; 95% CI 3.2-4.1) to 8-weeks follow-up (2.6; 95% CI 2.1-3.1), (P < 0.01). Pain decreased 0.04 NRS (95% CI 0.02-0.05, P < 0.01) on average per exercise session and pre- to post-exercise pain decreased 0.04 NRS (95% CI 0.03-0.05, P < 0.01) on average per session, approaching no acute exercise-induced pain in the last weeks. CONCLUSION: This study found a clear decrease in size of acute exercise-induced pain flares with increasing number of exercise sessions. In parallel, pain ratings decreased over the 8 weeks exercise period. Our findings provide helpful information for clinicians, which can be used to educate and balance patient expectation when starting supervised neuromuscular exercise. PMID- 26564574 TI - Differences in subchondral bone size after one year in osteoarthritic and healthy knees. AB - OBJECTIVE: Increase of subchondral bone area (tAB) in OA has been reported, but it remains unclear if this is specific to OA. We investigated differences in knee tAB after one year in healthy subjects and in those with radiographic OA (rOA). METHOD: MR images of 899 right knees from the OA Initiative were acquired at baseline and one year follow-up (year-1). Medial and lateral tibial cartilage (MT and LT) and weight-bearing femoral cartilage (cMF and cLF) were segmented and tAB computed. Subjects were stratified into: healthy controls, pre-rOA (K&L grades 0 and 1, with OA risk factors), established rOA (K&L grades 2-4), and independently with regards to joint space narrowing (without, with medial, lateral and bilateral JSN). Primary analysis tested if tAB was different between baseline and year-1 in rOA. Exploratory analyses investigated whether: (1) tAB changes differed between healthy controls and those with rOA; (2) tAB differences were greater in higher K&L grades; and (3) tAB was different between baseline and year 1 in JSN. Significance was set at P < 0.0125. RESULTS: Differences in tAB were found in rOA in MT, cMF and cLF (ranging from +0.2% to +0.4%; P < 0.001), but not in healthy controls or pre-rOA. Rates of change did not differ between groups. Within the JSN groups differences of 0.2-0.4% were found in the femur (P < 0.05). CONCLUSION: We find that knee tABs differ in rOA between baseline and year-1, but the change was not greater than in healthy knees, and is restricted to the femur in JSN. PMID- 26564576 TI - Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative. AB - OBJECTIVES: To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). DESIGN: Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. RESULTS: Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. CONCLUSIONS: Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR. PMID- 26564577 TI - Characterizing the thymic lesions in piglets infected with attenuated strains of highly pathogenic porcine reproductive and respiratory syndrome virus. AB - Piglets infected with the highly pathogenic PRRSV (HP-PRRSV) HuN4 strain develop severe thymus atrophy. However, the attenuated strain HuN4-F112 does not lead to lesions in organs. Here, we have characterized the thymic lesions in piglets infected with attenuated strains of HP-PRRSV HuN4 isolated at different passages in the attenuation process to produce HuN4-F112 from the parent HuN4 strain (HuN4 F5, HuN4-F15, HuN4-F23, HuN4-F30, and HuN4-F112). The thymic effects of infection were evaluated in terms of the thymus/body weight ratio, pathological changes, and thymocytes apoptosis. The ability of HP-PRRSV to induce thymus atrophy was reduced following attenuation after 23 passages; the HuN4-F23, but not HuN4-F30, caused thymus atrophy. The ability of the virus to induce thymocyte apoptosis decreased as it became attenuated. In addition, the viral load in the thymus was reduced as the virus was attenuated. The HuN4-F23 and HuN4-F30 strains might provide insight into the molecular mechanisms of HP-PRRSV pathogenesis. Taken together, our results indicate that the ability of HP-PRRSV to induce thymic atrophy is related to its pathogenicity. PMID- 26564578 TI - AmrZ regulates cellulose production in Pseudomonas syringae pv. tomato DC3000. AB - In Pseudomonas syringae pv. tomato DC3000, the second messenger c-di-GMP has been previously shown to stimulate pellicle formation and cellulose biosynthesis. A screen for genes involved in cellulose production under high c-di-GMP intracellular levels led to the identification of insertions in two genes, wssB and wssE, belonging to the Pto DC3000 cellulose biosynthesis operon wssABCDEFGHI. Interestingly, beside cellulose-deficient mutants, colonies with a rougher appearance than the wild type also arouse among the transposants. Those mutants carry insertions in amrZ, a gene encoding a transcriptional regulator in different Pseudomonas. Here, we provide evidence that AmrZ is involved in the regulation of bacterial cellulose production at transcriptional level by binding to the promoter region of the wssABCDEFGHI operon and repressing cellulose biosynthesis genes. Mutation of amrZ promotes wrinkly colony morphology, increased cellulose production and loss of motility in Pto DC3000. AmrZ regulon includes putative c-di-GMP metabolising proteins, like AdcA and MorA, which may also impact those phenotypes. Furthermore, an amrZ but not a cellulose-deficient mutant turned out to be impaired in pathogenesis, indicating that AmrZ is a key regulator of Pto DC3000 virulence probably by controlling bacterial processes other than cellulose production. PMID- 26564579 TI - Vibrato Rate and Extent in College Music Majors: A Multicenter Study. AB - OBJECTIVES: To examine differences in vibrato rate and extent according to vowel, production type, gender, voice type, and vocal training. STUDY DESIGN: Cross sectional. METHODS: Four collegiate voice teachers used a common protocol to gather data on habitual, best classical, and nonvibrato singing production of five vowels in 78 male and female vocal majors. Subject age, gender, voice type, academic degree program, number of years of training, and most frequent singing style were compared with mean vibrato rate and mean peak-to-peak vibrato extent for each vowel and for each production condition. RESULTS: The high versus low and female versus male comparisons in this study support results found in the literature. Both vibrato rate and vibrato extent were reduced when the singers sang nonvibrato as compared with their habitual and best classical production. CONCLUSIONS: The mechanisms for reducing vibrato rate and extent need further exploration. PMID- 26564580 TI - Interactive Augmentation of Voice Quality and Reduction of Breath Airflow in the Soprano Voice. AB - In 1985, at a conference sponsored by the National Institutes of Health, Martin Rothenberg first described a form of nonlinear source-tract acoustic interaction mechanism by which some sopranos, singing in their high range, can use to reduce the total airflow, to allow holding the note longer, and simultaneously enrich the quality of the voice, without straining the voice. (M. Rothenberg, "Source Tract Acoustic Interaction in the Soprano Voice and Implications for Vocal Efficiency," Fourth International Conference on Vocal Fold Physiology, New Haven, Connecticut, June 3-6, 1985.) In this paper, we describe additional evidence for this type of nonlinear source-tract interaction in some soprano singing and describe an analogous interaction phenomenon in communication engineering. We also present some implications for voice research and pedagogy. PMID- 26564581 TI - The Effects of Expiratory Muscle Strength Training on Voice and Associated Factors in Medical Professionals With Voice Disorders. AB - OBJECTIVES: This research used expiratory muscle strength training to explore the factors relevant to medical professionals with voice disorders. The maximal expiratory pressure (MEP) improved, which is measured by the maximal contracting force of expiratory muscles. The expiratory muscle strength increased, which can affect the positive pressure of pulmonary volume, thereby influencing subglottal pressure for speech to change the voice performance and vocal-fold vibration. METHODS: Twenty-nine participants with voice disorders who are working in a hospital and who are using their voice for more than 4 hours per day were recruited. The participants were randomly assigned to either the study group (STU) or the control group (CON). All participants underwent aerodynamics analysis, pulmonary function, MEP, and completed a vocal symptoms questionnaire before and after STU was provided. The interventions in the STU were conducted 3 days per week and involved performing 25 expiratory exercises (five cycles, each comprising five breaths) for 5 weeks. The CON did not receive any intervention. RESULTS: The voiceless /S/ expiratory time, symptom questionnaire scores, and MEP were greater in the STU than in the CON (P < 0.05). However, no statistically significant difference in the results of the pulmonary function was observed between the groups. The STU exhibited a greater percentage change in maximal voiced /Z/ phonation and voiceless /S/ expiratory compared with the CON (P < 0.05). CONCLUSIONS: The participants' voiceless /S/ expiratory time, symptom questionnaire scores, and MEP significantly improved after the intervention. Future studies can increase the number of participants, increase the number of study groups, and examine the effectiveness of long-term treatment. PMID- 26564582 TI - The Spatial Distribution of Nitrogen Removal Functional Genes in Multimedia Constructed Wetlands for Wastewater Treatment. AB - The real-time polymerase chain reaction was used to quantitatively evaluate distribution patterns and nitrogen removal pathways of the amoA, nxrA, narG, napA, nirK, qnorB, nosZ, nas, and nifH genes and 16S rRNA in anaerobic ammonia oxidation bacteria in four multimedia constructed wetlands for rural wastewater treatment. The results indicated that the abundance of functional genes for nitrogen removal in the rhizosphere layer (0 to 30 cm), water distribution layer (30 to 50 cm), multime filler layer (50 to 130 cm), and catchment layer (130 to 170 cm) of the constructed wetlands were closely related. The rhizosphere layer was conducive to the absolute enrichment of dominant genes. The other three layers were favorable to the relative enrichment of rare genes. PMID- 26564583 TI - Effects of Biocide Chlorine on Biochemical Responses of the Dinoflagellate Prorocentrum minimum. AB - Effects of the biocide sodium hypochlorite (NaOCl) on the dinoflagellate Prorocentrum minimum were assessed. Growth rate, pigment concentrations, and chlorophyll autofluorescence were monitored up to 72 hours after NaOCl exposure, and these parameters showed dose- and time-dependent decrease. The 72-hour EC50 was 0.983 mg/L. Additionally, enzymatic activities of lipid peroxidation and reduced glutathione were significantly altered with increasing NaOCl and exposure time. Thus, NaOCl at doses of 0.5 mg/L induces physiological and biochemical changes in P. minimum, suggesting that chlorine concentrations observed in power plant discharges and in drinking water systems are potentially detrimental to microalgae. PMID- 26564584 TI - Comprehensive Numerical Modeling of Greenhouse Gas Emissions from Water Resource Recovery Facilities. AB - A numerical model was developed to comprehensively predict greenhouse gas (GHG) emissions from water resource recovery facilities. An existing activated sludge model was extended to include a nitrifier-denitrification process and carbon dioxide (CO2) as a state variable. The bioreactor model was coupled to a process based digester model and an empirical model of indirect CO2emissions. Direct emissions were approximately 90% of total GHG emissions for a plantwide simulation using the Modified Ludzack-Ettinger process. Biogenic CO2, nitrous oxide (N2O), and methane (CH4) represented 10, 43, and 34% of total emissions. Simulating a dissolved oxygen controlled closed-loop system reduced both sensitivity and uncertainty of GHG emissions. Nitrous oxide emissions were much more sensitive under different design and operating conditions compared to CH4and CO2, indicating a significant mitigation potential. An uncertainty analysis found that the uncertainty in GHGs emissions estimates could be significant. Nitrous oxide emissions dominated in both magnitude and uncertainty. PMID- 26564585 TI - Determination of Trophic State Changes with Diel Dissolved Oxygen: A Case Study in a Shallow Lake. AB - Current trophic state indices (TSI) have been reported to have limitations in assessing changes in eutrophication status of shallow waters. This study aimed to use intensive measurements on dissolved oxygen (DO) to improve the determination of tropic state changes. The authors deployed an environment monitoring buoy in a eutrophic shallow lake and recorded water temperature, DO, and chlorophyll-a concentrations at 15-minute intervals for two 1-year periods: from August 2008 to July 2009 and from August 2013 to July 2014. In addition, they recorded water levels over the same periods and collected water samples for nutrient analysis. The authors analyzed the high-time resolution DO records, compared the diel DO trends between the two 1-year periods, and proposed a new TSI using DO. They found that analyzing the change in diel DO ranges can improve commonly used methods for classifying trophic states and assessing the change of eutrophication status of waterbodies. PMID- 26564586 TI - Modeling Sulfides, pH and Hydrogen Sulfide Gas in the Sewers of San Francisco. AB - An extensive measuring campaign targeted on sewer odor problems was undertaken in San Francisco. It was assessed whether a conceptual sewer process model could reproduce the measured concentrations of total sulfide in the wastewater and H2S gas in the sewer atmosphere, and to which degree such simulations have potential for further improving odor and sulfide management. The campaign covered measurement of wastewater sulfide by grab sampling and diurnal sampling, and H2S gas in the sewer atmosphere was logged. The tested model was based on the Wastewater Aerobic/Anaerobic Transformations in Sewers (WATS) sewer process concept, which never had been calibrated to such an extensive dataset. The study showed that the model was capable of reproducing the general levels of wastewater sulfide, wastewater pH, and sewer H2S gas. It could also reproduce the general variability of these parameters, albeit with some uncertainty. It was concluded that the model could be applied for the purpose in mind. PMID- 26564587 TI - Resilience of Groundwater Impacted by Land Use and Climate Change in a Karst Aquifer, South China. AB - Changes of groundwater flow and quality were investigated in a subtropical karst aquifer to determine the driving mechanism. Decreases in groundwater flow are more distinct in discharge zones than those in recharge and runoff zones. Long term measurement of the represented regional groundwater outlet reveals that groundwater discharge decrease by nearly 50% during the dry season. The hydrochemistry of groundwater in the runoff and discharge zones is of poorer quality than in the recharge zone. Indications of intensive land resource exploitation and changes in land use patterns were attributed to changes in groundwater conditions since 1990, but the influence of climate change was likely from 2001, because the water temperature exhibited increasing trends at a mean rate of 0.02 degrees C/yr even though groundwater depth was high in the aquifer. These conclusions imply the need for further groundwater monitoring and reevaluation to understand the resilience of aquifer during urbanization and development. PMID- 26564588 TI - Nitrogen and COD Removal from Septic Tank Wastewater in Subsurface Flow Constructed Wetlands: Plants Effects. AB - We evaluated subsurface flow (SSF) constructed wetland treatment performance with respect to organics (COD) and nitrogen (ammonium and nitrate) removal from domestic (septic tank) wastewater as affected by the presence of plants, substrate "rock" cation exchange capacity (CEC), laboratory versus field conditions and use of synthetic as compared to actual domestic wastewater. This article considers the effects of plants on constructed wetland treatment in the field. Each constructed wetland system was comprised of two beds (2.6 m long by 0.28 m wide and deep filled with ~18 mm crushed lava rock) separated by an aeration tank connected in series. The lava rock had a porosity of ~47% and a CEC of 4 meq/100 gm. One pair of constructed wetland systems was planted with cattails in May 2008, while an adjacent pair of systems remained un-planted. Collected septic tank or synthesized wastewater was allowed to gravity feed each constructed wetland system and effluent samples were regularly collected and tested for COD and nitrogen species during four time periods spanning November 2008 through June 2009. These effluent concentrations were tested for statistical differences at the 95% level for individual time periods as well as the overall 6 month period. Organics removal from domestic wastewater was 78.8% and 76.1% in the planted and un-planted constructed wetland systems, respectively, while ammonium removal was 94.5% and 90.2%, respectively. Similarly, organics removal from the synthetic wastewater of equivalent strength was 88.8% and 90.1% for planted and un-planted constructed wetland systems, respectively, while ammonium removal was 96.9% and 97.3%, respectively. PMID- 26564589 TI - Evaluation of Genotoxic Potential of Waters from Two Italian Rivers in Gammarus elvirae (Amphipoda). AB - The aim of the present work is to evaluate the genotoxic impact of contaminants along the whole course of Ninfa-Sisto and Amaseno (Latium, Italy) rivers. The authors performed the alkaline Comet assay to assess DNA damage in the freshwater amphipod Gammarus elvirae, exposed ex situ for 24 hours and 7 days to water collected at different sites. The assay, applied on haemocytes, provides a sensitive tool to reveal effects even at low concentrations of pollutants. The results indicate significant increase of DNA damage along the course of the two rivers, compared to the unpolluted upstream sites, even if the analytes do not exceed the permissible limits. Moreover, the results show that there is not a linear correlation between the concentration of analytes and DNA damage. Based on this study's results, it would be desirable to use Comet assay, on proposed test species, as an early warning method to detect genotoxic potential of waters. PMID- 26564590 TI - Competitive Adsorption and Oxidation Behavior of Heavy Metals on nZVI Coated with TEOS. AB - Zero valent iron nanoparticle (nanofer ZVI) is a powerful substance due to its coating with tetraethyl orthosilicate (TEOS). Tetraethyl orthosilicate imparts higher reactivity and decreases particle agglomeration. The competitive removal and displacement of multi-metals are influenced by time, pH, and initial concentration, the presence and properties of competing metals ion in the solution. For both the isotherm and kinetic studies performed for multi-metal removal experiments, compared to Pb II and Cd II, Cu II experienced a higher removal rate during the initial 5 minutes. After 120 minutes, all metals achieved removal efficiency in the range of 95 to 99%. The results of single and competitive kinetic tests for all three metals during the initial 5 minutes indicated that the presence of other metals generally reduce removal efficiency of metals. Both kinetic test and electron dispersive spectroscope (EDS) studies found that Cu II gets removed faster than the other metals. Pseudo-second order behavior was noted for the multi-metal removal systems. PMID- 26564591 TI - Heavy Metal Contamination of Soil, Irrigation Water and Vegetables in Peri-Urban Agricultural Areas and Markets of Delhi. AB - Dietary exposure to heavy metals, namely cadmium (Cd), lead (Pb), zinc (Zn), and copper (Cu), has been identified as a risk to human health through consumption of vegetable crops. The present study investigates heavy metal contamination in irrigation water, soil, and vegetables at four peri-urban and one wholesale site in Delhi, India, and estimates the health risk index. Most of the samples collected from peri-urban areas exceeded the safe limits of lead and cadmium, whereas only lead concentration was found to be higher in vegetable samples collected from the wholesale market. Average uptake of metals by vegetables from soil decreased in the order Cd>Zn>Cu>Pb. The order of metal uptake based on transfer factor was highest in okra, cauliflower, and spinach, from greatest to least. Among the vegetables from peri-urban sites, only okra crossed the safe limit for cadmium; whereas vegetables from the wholesale site exceeded the limit for lead (potato, coriander, chilies, pea, and carrot, in order from greatest to least) with respect to health risk index. PMID- 26564593 TI - Masked and White-Coat Hypertension: Moving to African Americans. PMID- 26564592 TI - Target Organ Complications and Cardiovascular Events Associated With Masked Hypertension and White-Coat Hypertension: Analysis From the Dallas Heart Study. AB - BACKGROUND: Multiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States. OBJECTIVES: The goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, >=140/90 mm Hg; normal home BP, <135/85 mm Hg), MH (high home BP, >=135/85 mm Hg; normal clinic BP, <140/90 mm Hg), and sustained hypertension (high home and clinic BP) in the DHS (Dallas Heart Study), a large, multiethnic, probability-based population cohort. METHODS: Associations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed. RESULTS: The study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors. CONCLUSIONS: In a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults. PMID- 26564594 TI - The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk. AB - BACKGROUND: Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. OBJECTIVES: This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. METHODS: We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. RESULTS: Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. CONCLUSIONS: Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality. PMID- 26564595 TI - Pro-Arrhythmic Effects of Noncardiac Medications: Lessons From Macrolide Antibiotics. PMID- 26564597 TI - Carcinoid Heart Disease: The Challenge of the Unknown Known. PMID- 26564596 TI - Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease. AB - BACKGROUND: Symptoms and survival of patients with carcinoid syndrome have improved, but development of carcinoid heart disease (CaHD) continues to decrease survival. OBJECTIVES: This study aimed to analyze patient outcomes after valve surgery for CaHD during a 27-year period at 1 institution to determine early and late outcomes and opportunities for improved patient care. METHODS: We retrospectively studied the short-term and long-term outcomes of all consecutive patients with CaHD who underwent valve replacement at our institution between 1985 and 2012. RESULTS: The records of 195 patients with CaHD were analyzed. Pre operative New York Heart Association class was III or IV in 125 of 178 patients (70%). All had tricuspid valve replacement (159 bioprostheses, 36 mechanical), and 157 underwent a pulmonary valve operation. Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). There were 20 perioperative deaths (10%); after 2000, perioperative mortality was 6%. Survival rates (95% confidence intervals) at 1, 5, and 10 years were 69% (63% to 76%), 35% (28% to 43%), and 24% (18% to 32%), respectively. Overall mortality was associated with older age, cytotoxic chemotherapy, and tobacco use; 75% of survivors had symptomatic improvement at follow-up. Presymptomatic valve operation was not associated with late survival benefit. CONCLUSIONS: Operative mortality associated with valve replacement surgery for CaHD has decreased. Symptomatic and survival benefit is noted in most patients when CaHD is managed by an experienced multidisciplinary team. PMID- 26564598 TI - Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. AB - BACKGROUND: Potent cholesteryl ester transfer protein (CETP) inhibitors have been shown to substantially increase high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels as monotherapy and combined with statins. However, data on the effects of this class of drugs on macrophage cholesterol efflux capacity (CEC), a functional assay that characterizes a key step in the process of reverse cholesterol transport, are limited. OBJECTIVES: This study assessed the impact of evacetrapib, statins, or combination therapy on CEC. METHODS: We analyzed samples from 377 subjects with elevated low-density lipoprotein cholesterol (LDL-C) or low HDL-C levels who were enrolled in a phase 2 trial of evacetrapib. Percent changes from baseline in CEC (total, non-ABCA1-, and ABCA1-specific) and HDL subpopulations were evaluated after 12 weeks of treatment with placebo, statin monotherapy, evacetrapib monotherapy, or evacetrapib combined with statins. Pre beta-1 HDL levels were quantified by immunofixation and nondenaturing 2 dimensional gel electrophoresis (2DGE). RESULTS: Relative to placebo, evacetrapib monotherapy increased dose-dependent total and non-ABCA1-specific CEC up to 34% and 47%, respectively. Evacetrapib monotherapy also increased ABCA1-specific CEC up to 26%. Relative to statin monotherapy, evacetrapib with statins also increased total, non-ABCA1-, and ABCA1-specific CEC by 21%, 27%, and 15%, respectively. In contrast, rosuvastatin and simvastatin significantly reduced total and ABCA1-specific CEC, whereas atorvastatin had no significant effect. Consistent with ABCA1-specific CEC, evacetrapib monotherapy and evacetrapib combined with statins significantly increased pre-beta-1 HDL levels as measured by either method. CONCLUSIONS: Evacetrapib, as monotherapy and combined with statins, not only increased total CEC, but also increased ABCA1-specific CEC and pre-beta-1 HDL. The mechanisms by which potent CETP inhibition increases ABCA1 specific CEC and pre-beta-1 HDL require further study. (A Study of LY2484595 in Patients With High LDL-C or Low HDL-C; NCT01105975). PMID- 26564599 TI - Cholesterol Efflux Capacity as a Therapeutic Target: Rationale and Clinical Implications. PMID- 26564601 TI - MicroRNA Augmentation of Bone Marrow-Derived Cell Therapy. PMID- 26564600 TI - Enhanced Cardiac Regenerative Ability of Stem Cells After Ischemia-Reperfusion Injury: Role of Human CD34+ Cells Deficient in MicroRNA-377. AB - BACKGROUND: MicroRNA (miR) dysregulation in the myocardium has been implicated in cardiac remodeling after injury or stress. OBJECTIVES: The aim of this study was to explore the role of miR in human CD34(+) cell (hCD34(+)) dysfunction in vivo after transplantation into the myocardium under ischemia-reperfusion (I-R) conditions. METHODS: In response to inflammatory stimuli, the miR array profile of endothelial progenitor cells was analyzed using a polymerase chain reaction based miR microarray. miR-377 expression was assessed in myocardial tissue from human patients with heart failure (HF). We investigated the effect of miR-377 inhibition on an hCD34(+) cell angiogenic proteome profile in vitro and on cardiac repair and function after I-R injury in immunodeficient mice. RESULTS: The miR array data from endothelial progenitor cells in response to inflammatory stimuli indicated changes in numerous miR, with a robust decrease in the levels of miR-377. Human cardiac biopsies from patients with HF showed significant increases in miR-377 expression compared with nonfailing control hearts. The proteome profile of hCD34(+) cells transfected with miR-377 mimics showed significant decrease in the levels of proangiogenic proteins versus nonspecific control-transfected cells. We also validated that serine/threonine kinase 35 is a target of miR-377 using a dual luciferase reporter assay. In a mouse model of myocardial I-R, intramyocardial transplantation of miR-377 silenced hCD34(+) cells in immunodeficient mice, promoting neovascularization (at 28 days, post-I R) and lower interstitial fibrosis, leading to improved left ventricular function. CONCLUSIONS: These findings indicate that HF increased miR-377 expression in the myocardium, which is detrimental to stem cell function, and transplantation of miR-377 knockdown hCD34(+) cells into ischemic myocardium promoted their angiogenic ability, attenuating left ventricular remodeling and cardiac fibrosis. PMID- 26564602 TI - Percutaneous Pulmonary Valve Implantation: Present Status and Evolving Future. AB - Due to recurrent right ventricular outflow tract (RVOT) dysfunction, patients with complex congenital heart disease of the RVOT traditionally require multiple surgical interventions during their lifetimes. Percutaneous pulmonary valve implantation (PPVI) has been developed as a nonsurgical alternative for the treatment of right ventricular to pulmonary artery stenosis or pulmonary regurgitation. PPVI has been shown to be a safe and effective procedure in patients with dysfunctional surgical RVOT conduits. In this population, PPVI has the potential to improve symptoms, functional capacity, and biventricular hemodynamics. However, limitations to the anatomical substrate and size of the RVOT currently restrict PPVI eligibility to less than one-quarter of patients with RVOT dysfunction. The current review discusses contemporary practices in PPVI, evidence supporting the procedure, and future technologies and developments in the field. PMID- 26564603 TI - American College of Cardiology Advocacy: Ensuring Value in a Value-Based Health System. PMID- 26564604 TI - Further Investigating JACC's Vision of Simplicity: Understanding the Meaning Behind the Central Illustration. PMID- 26564605 TI - How Young Cardiologists Can Succeed in the Era of Population Health. PMID- 26564606 TI - BMI Reduction Decreases AF Recurrence Rate in a Mediterranean Cohort. PMID- 26564607 TI - Reply: BMI Reduction Decreases AF Recurrence Rate in a Mediterranean Cohort. PMID- 26564608 TI - Duration of Triple Therapy: A Clinical Question Yet to Be Answered. PMID- 26564609 TI - Reply: Duration of Triple Therapy: A Clinical Question Yet to Be Answered. PMID- 26564610 TI - Living Up to the PROMISE: Is There an Ultimate Winner? PMID- 26564611 TI - Radiation Dose to the Penile Structures and Patient-Reported Sexual Dysfunction in Long-Term Prostate Cancer Survivors. AB - AIM: The involvement of various penile structures in radiotherapy (RT)-induced sexual dysfunction among prostate cancer survivors remains unclear and domains beyond erectile dysfunction such as orgasm, and pain have typically not been considered. The purpose of this study was to investigate sexual dysfunction post RT for localized prostate cancer and to examine whether radiation dose to different penile structures can explain these symptoms. METHODS: We investigated sexual dysfunction in two treated prostate cancer cohorts and in one non-pelvic irradiated cohort, 328 sexually active men part of an unselected, population based study conducted in 2008. The treated subjects were prescribed primary/salvage external-beam RT to 70 Gy@2.0 Gy/fraction. Absorbed RT doses (Dmean and Dmax ) of the corpora cavernosa (CC), the penile bulb (PB), and the total penile structure (CC + PB) were related to 13 patient-reported symptoms on sexual dysfunction by means of factor analysis (FA) and logistic regression. RESULTS: Three distinct symptom domains were identified across all cohorts: "erectile dysfunction" (ED, two to five symptoms), "orgasmic dysfunction" (OD, two to four symptoms), and "pain" (two to three symptoms). The strongest predictor for ED symptoms was CC + PB Dmax (P = 0.001-0.03), CC and PB Dmean predicted OD symptoms equally well (P = 0.03 and 0.02-0.05, respectively), and the strongest predictor for pain symptoms was CC + PB Dmean (P = 0.02-0.03). CONCLUSION: Sexual dysfunction following RT was separated into three main domains with symptoms related to erectile dysfunction, orgasmic dysfunction, and pain. Chances for intact sexual functionality may be increased if dose to the total penile structure can be restricted for these domains in the planning of RT . PMID- 26564612 TI - Seatbelt syndrome with superior mesenteric artery syndrome: leave nothing to chance! AB - The introduction of seatbelts to legislation has dramatically reduced mortality and morbidity from motor vehicle accidents. However, overtime evidence has emerged of 'seatbelt syndrome' (SBS), particularly in the paediatric population. The report describes the diagnosis and management of this rare injury in a 12 year-old boy who sustained a chance lumbar fracture and mesenteric tear resulting in small bowel obstruction. His stay was subsequently complicated by superior mesenteric artery (SMA) syndrome. This is the first documented case of SBS with SMA syndrome. High index of suspicion and continuity of care, particularly in the setting of a 'seatbelt sign', is paramount to timely diagnosis and management. PMID- 26564613 TI - MRI of wrist and hand masses. AB - Hand and wrist masses represent a common diagnostic challenge. They are predominantly due to pseudomasses, which are mostly cysts and to benign masses that include tenosynovial tumors, fibrohamartolipomas, vascular malformations, glomus tumors and epidermal inclusion cysts. Malignant tumors of the wrist and the hand are extremely rare. Magnetic resonance imaging is the imaging technique of choice to characterize and circumscribe lesions to determine the best treatment option. PMID- 26564614 TI - Traumatic flexor tendon injuries. AB - The flexor system of the fingers consisting of flexor tendons and finger pulleys is a key anatomic structure for the grasping function. Athletes and manual workers are particularly at risk for closed injuries of the flexor system: ruptured pulleys, ruptures of the flexor digitorum profundus from its distal attachment ("jersey finger"), and less frequently, ruptures of the flexor digitorum superficialis and of the lumbrical muscles. Open injuries vary more and their imaging features are more complex since tendons may be torn in several locations, the locations may be unusual, the injuries may be associated with nerve and vascular injuries, fibrosis... Sonography is the best imaging modality to associate with the clinical exam for it allows an experienced physician to make an accurate and early diagnosis, crucial to appropriate early treatment planning. PMID- 26564615 TI - Extraperitoneal ascending appendicitis: Usefulness of the split interfascial plane sign on MDCT. AB - PURPOSE: To retrospectively evaluate the multidetector computed tomography (MDCT) findings of extraperitoneal ascending appendicitis. MATERIALS AND METHODS: The MDCT examinations of 10 patients with extraperitoneal ascending appendicitis confirmed by laparoscopic surgery were retrospectively analyzed. Preoperative MDCT examinations were obtained after intravenous administration of iodinated contrast material in all patients. Transverse and coronal reformatted MDCT images were reviewed in consensus by two radiologists. The presence of the extraperitoneal triangle sign, the split interfascial plane sign, and the other classical findings of appendicitis were evaluated. RESULTS: Luminal dilatation, wall enhancement of the inflamed appendix, and fat infiltration were present in 10/10 patients (100%). The perforation of the inflamed appendix with abscess formation was present in 4/10 patients (40%). The split interfascial plane sign was present in 7/10 patients (70%), and parts of inflamed appendix or periappendiceal abscess were located behind the right extraperitoneal triangle in 8/10 patients (80%). CONCLUSION: The split interfascial plane sign and the presence of an appendiceal tip or periappendiceal abscess located in the right extraperitoneal triangle are highly suggestive of extraperitoneal ascending appendicitis on MDCT. PMID- 26564616 TI - Tumors and pseudotumors of the hand: The role of imaging. AB - The assessment of a swelling or mass of the wrist or the hand is commonly performed by radiologists. Because cysts on the wrist are, by far, the most frequent pathology. Diagnosis is usually based on standard radiography and ultrasound alone. Additional imaging techniques, and in particular MR imaging, are necessary to assess tumors, although malignant tumors of the hand are rare. Some benign cysts have pathognomonic characteristics visible on imaging. By understanding them, treatment planning may be improved. PMID- 26564617 TI - Consonant accuracy in Mandarin-speaking children with repaired cleft palate. AB - OBJECTIVE: To compare the consonant production of Chinese-speaking cleft palate children with perceived hypernasal resonance (PHR) after palatoplasty and those with perceived normal resonance (PNR), and to assess the possible influence of language on articulation. SETTING: Two hospital cleft lip and palate centers in mainland China. PARTICIPANTS: Thirty-one speakers were allocated into two groups based on perceptual judgment results of their resonance provided by three speech therapists: one group with PNR (n=20, average age=9.3 years), and another group with PHR (n=11, average age=8.3 years). All participants had no known hearing or cognitive deficits. INTERVENTION: Articulation was evaluated using two Mandarin Chinese assessment tools, the Putonghua Segmental Phonology Test and the Deep Test for Cleft Palate Speakers in Putonghua. Speaker consonant accuracy was evaluated by two experienced speech therapists. RESULTS: Compared to individuals with PNR, the PHR group exhibited more difficulties on production of unaspirated consonants, including/b/,/t/,/k/,/ts/,/ts/ and/tc/, than for aspirated consonants. CONCLUSION: The distinctive feature of aspiration in Mandarin phonology brought a language specific pattern to consonant production among those speakers with PHR after primary palatal closure. PMID- 26564619 TI - Pulmonary Artery Pulsatility Index Is Associated With Right Ventricular Failure After Left Ventricular Assist Device Surgery. AB - BACKGROUND: Right ventricular failure (RVF) is a major cause of morbidity and mortality after CF-LVAD implantation. We explored the association of pulmonary artery compliance (PAC), pulmonary artery elastance (PAE), and pulmonary artery pulsatility index (PAPi) in addition to established parameters as preoperative determinants of postoperative RVF after CF-LVAD surgery. METHODS AND RESULTS: We retrospectively reviewed 132 consecutive CF-LVAD implantations at Tufts Medical Center from 2008 to 2013. Clinical, hemodynamic, and echocardiographic data were studied. RVF was defined as the unplanned need for a right ventricular assist device or inotrope dependence for >=14 days. Univariate analysis was performed. RVF occurred in 32 of 132 patients (24%). PAC and PAE were not changed, whereas the PAPi was lower among patients with versus without postoperative RVF (1.32 +/- 0.46 vs 2.77 +/- 1.16; P < .001). RA pressure, RA to pulmonary capillary wedge pressure ratio (RA:PCWP), and RV stroke work index (RVSWI) were also associated with RVF. Using receiver operating characteristic curve-derived cut-points, PAPi < 1.85 provided 94% sensitivity and 81% specificity (C-statistic = 0.942) for identifying RVF and exceeded the predictive value of RA:PCWP, RVSWI, or RA pressure alone. CONCLUSIONS: PAPi is a simple hemodynamic variable that may help to identify patients at high risk of developing RVF after LVAD implantation. PMID- 26564618 TI - Prediction of Acute Response to Cardiac Resynchronization Therapy by Means of the Misbalance in Regional Left Ventricular Myocardial Work. AB - BACKGROUND: Patients with left ventricular (LV) dyssynchrony have a marked misbalance in LV myocardial work distribution, with wasted work in the septum and increased work in the lateral wall. We hypothesized that a low septum-to-lateral wall (SL) myocardial work ratio at baseline predicts acute LV pump function improvement during cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Twenty patients (age 65 +/- 10 y, 15 men) underwent cardiac magnetic resonance (CMR) tagging for regional LV circumferential strain assessment and invasive pressure-volume loop assessment at baseline and during biventricular pacing. Segmental work at baseline was calculated from regional strain rate and LV pressure. Subsequently, the SL work ratio was calculated and related to acute pump function (stroke work [SW]) improvement during CRT. During biventricular pacing, SW increased by 33% (P <.001). SL work ratio at baseline was found to be significantly related to SW improvement by means of CRT (R = -0.54; P = .015). Moreover, it proved to be the only marker that was significantly related to acute response to CRT, whereas QRS duration and other measures of dyssynchrony or dyscoordination were not. CONCLUSIONS: The contribution of the septum to LV work varies widely in CRT candidates with left bundle branch block. The lower the septal contribution to myocardial work at baseline, the higher the acute pump function improvement that can be achieved during CRT. PMID- 26564620 TI - [Molecular epidemiology of HIV in China: 1985-2015]. PMID- 26564621 TI - [Development of an index system for the comprehensive evaluation on public health emergency events surveillance system in China]. AB - OBJECTIVE: To establish a comprehensive evaluation index system for the China Public Health Emergency Events Surveillance System (CPHEESS). METHODS: A draft index system was built through literature review and under the consideration of the characteristics on CPHEESS. Delphi method was adapted to determine the final index system. RESULTS: The index system was divided into primary, secondary and tertiary levels. There were 4 primary indicators: System structure, Network platform, Surveillance implementation reports with Data analysis and utilization. There were 16 secondary and 70 tertiary indicators being set, with System structure including 14 tertiary indicators (accounted for 20.00%), 21 Network platforms (accounted for 30.00%). Twenty-four Surveillance implementation reports (accounted for 34.29%), 11 Data analysis and utilization (accounted for 15.71%). The average score of importance of each indicators was 4.29 (3.77-4.94), with an average coefficient variation as 0.14 (0.12-0.16). The mean Chronbach's alpha index was 0.84 (0.81-0.89). The adaptability of each related facilities indicator was specified. CONCLUSION: The primary indicators were set in accordance with the characteristics and goals of the surveillance systems. Secondary indicators provided key elements in the management and control of the system while the tertiary indicators were available and operative. The agreement rate of experts was high with good validity and reliability. This index system could be used for CPHEESS in future. PMID- 26564622 TI - [Difference on sleeping between school-days and weekends in elementary school children, data from 8 provinces in China]. AB - OBJECTIVE: To understand the differences on sleeping-time between school-days and weekends among elementary school children. METHODS: This cross-sectional study was conducted from September to November, 2010. A stratified random cluster sampling strategy was used to select the participants, under diverse geographical and economic levels in eight provinces, municipalities or autonomous regions, in mainland China. A total number of 20 603 elementary school children aged from 6 12 years old were chosen as research subjects to record their time of sleeping during school-days or weekends. RESULTS: Among the 6-12 year old, their time of sleeping was longer on weekends than that on school-days, while the average sleeping time during the weekends was longer in boys than in girls (t = 3.35, P < 0.05). However, there was no linearly decreasing trend along with the increase of age regarding the time of sleeping on weekends, in girls. Proportions of serious lack of sleep, lack of sleep or with sufficient sleep during the weekends were 13.63% (2 809/20 603), 27.27% (5 618/20 603) and 59.10% (12 176/20 603). The proportion of sufficient sleep (over 50%) was significantly higher on weekends than that on school-days (less than 30%), however, nearly one third of the first grade primary school children were sleep insufficiently even on weekends. Nearly 10.00% of the children under seriously or moderately lack of sleep on school-days were still in a serious lack of sleep state on weekends. The three groups who were categorized as serious lack of sleep (less than 9 h), lack of sleep (9-10 h) or having sufficient (over 10 h) sleep on school-days accounted for 29.75%, 64.48%, 86.44%, respectively, when compared with the national regulation set as 10 h daily sleep for the children in China. The proportions of those whose time of sleep on weekends was less than school-days in the three groups as the same, moderate (within 1 h), with 1 h caught-up or over, were 9.41%, 22.77%, 43.32%, 24.50%, respectively. The percentage of pupils who caught up sleep appropriately (within 1 h) on weekends among those who were serious lack of sleep in school days would exceed 40.00% while the proportions among those who lack of sleep or having sufficient on school-days were 54.00% and 30.00%. The percentage of children who slept less on weekends than on school-days among those having sufficient sleep on school-days appeared the highest, nearly 20.00%. However, the proportions among those who lack of sleep or seriously lack of sleep on school days were 3.45% and 8.16%, respectively. CONCLUSION: We found that the elementary school children who could catch up time of sleep or lack of sleep on weekends coexisting in our study. This situation called for attention and the sleeping habit in primary school children should also be urgently improved. PMID- 26564623 TI - [Study on the variation of arsenic concentration in groundwater and chemical characteristics of arsenic in sediment cores at the areas with endemic arsenic poison disease in Jianghan Plain]. AB - OBJECTIVE: To understand the variation of arsenic concentration in underground water at the endemic arsenic poison disease area of Jianghan Plain so as to better understand the spatial distribution of high arsenic groundwater, hydro chemical evolution and source of arsenic in this region. METHODS: Thirty underground water samples were collected respectively around 3 km radius of the two houses where arsenic poisoning patients lived, in Xiantao and Honghu. Sediment cores of three drillings were collected as well. Both paired t-test or paired Wilcoxon Signed Ranking Test were used to compare the arsenic concentration of water. RESULTS: The arsenic concentration in 2011-2012 appeared lower than that in 2006-2007 at the Nanhong village of Xiantao (t = 4.645 3, P < 0.000 1), but was higher (S = -150, P < 0.000 1) in the Yaohe village of Honghu. The pH value showed weak acidity with Eh as weak oxidated. Positive correlations were observed between arsenic concentration and Cl, HCO3(-), Fe, Mn. However, negative correlations were found between As and SO4(2-), NO3(-). The range of arsenic content in the sediment was 1.500 mg/kg to 17.289 mg/kg. The maximum arsenic content existed in the soil layer, while the minimum arsenic content existed in the sand layer. CONCLUSION: The concentration of arsenic varied widely with time and space at endemic arsenic poison disease area of Jianghan Plain. Characteristics of these water chemicals showed significant differences, when compared to the groundwater from Datong Basin, Shanxi Shanyin and Hetao Plain of Inner Mongolia, which presented a typical environment with high arsenic contents in the groundwater. The arsenic content in the sediment samples seemed related to the lithologic structure. PMID- 26564624 TI - [Comprehensive assessment on the outcome of Tianjin Act of Tobacco Control]. AB - OBJECTIVE: To evaluate the integrated effects of tobacco control programs through comparing the pre- and post-implementation of the Tianjin Tobacco Control Act (Act), in 4 successive years. METHODS: Case-related data on myocardial infarction was collected by Tianjin Surveillance System, New Case Registry. Both the representative sample size of indoor working places and public places for observation and PM2.5 monitored were selected through the calculation of Survey System, while the representative sample size of people involved in the survey for interview was under the Door to Door and Intercept. RESULTS: Through comparing the pre- and post-implementation programs on Act, the posting of "No Smoking Sign" had become much more visible in hospitals, schools, governmental buildings and the waiting areas of public transportation. People smoked much less in the main public places, excepting for hotels and public bath rooms (P < 0.05). Exposure to secondhand smoking (SHS) had a 26.5% (P < 0.01) decline, than the Act was implemented in workplace and public place. Despite the number of cases increased in the entire population in Tianjin (beta = -0.061, P = 0.00; beta = 0.059, P = 0.00), cases with myocardial infarction presented at the hospitals were declining annually, among the indoor workers. CONCLUSION: Act showed a positive effect in decreasing the number of smokers in public places thus protecting people from the negative effects on SHS. Message on health effect and social benefits on tobacco control should be disseminated to facilitate the comprehensive implementation of the Act. PMID- 26564625 TI - [Study on spousal notification in HIV discordant couples and associated factors in four provinces of China]. AB - OBJECTIVE: This study was aimed to investigate the ways of spousal notification and its associated factors among HIV discordant couples. METHODS: A face-to-face questionnaire survey was conducted in Henan, Yunnan, Sichuan provinces and Guangxi Zhuang Autonomous Region in China. Information including democratic characteristics, knowledge and behaviors correlated with HIV infections and ways of HIV infectious status notification was collected. 'Data information system' on AIDS prevention and control was used to collect information on the transmission route. RESULTS: A total of 770 pairs of HIV discordant couples were studied, among which 414 (53.77%) HIV positive respondents reported as self-notification, with another 44.68% were notified by medical staff. Factors associated with ways of notification included gender, nation, transmission route, and education level. HIV positive respondents who were female, under Han nationality, being paid blood donors, having had higher education level, were more likely to inform their HIV negative spouse by themselves. CONCLUSION: Nationality and HIV transmission route of the HIV positive individuals were found as significant factors associated with ways of spousal notification. Therefore, HIV discordant couples notification should be strengthened, especially in the Minority-living areas and areas where HIV transmission was predomint through sexual contact and/or via injected drug use. PMID- 26564626 TI - [Survival time and related influencing factors of AIDS patients in Liangshan prefecture, Sichuan province, during 2008-2013]. AB - OBJECTIVE: To investigate the survival time and affecting factors among AIDS patients under antiretroviral treatment, between 2008 and 2013 in Liangshan, Sichuan province. METHODS: Observational retrospective cohort study method was applied. AIDS patients were chosen from China's national comprehensive prevention and control management system of AIDS in Liangshan, during 2008-2013. Related information on demographics, source of infection, pathogenesis, treatment and death was collected. Cox proportional hazards model was applied to analyze the factors that might affect the survival on patients. RESULTS: Among the 8 321 cases, ranging from 18 to 87.5 years old (mean age as 34.2 +/- 9.8), 3 021 died and 3 721 patients had received HAART treatment. The total mortality rate dropped from 43.9/100 person-years to 20.7/100 person-years from 2008 to 2013. In the treatment group, mortality rate dropped from 27.3/100 person-years to 5.1/100 person-years, while in the untreated group it remained high-between 45.0/100 50.8/100 person-years. Proportion for the treatment coverage increased gradually, from 5.8% in 2008 to 54.5% in 2013. Median survival time of all the AIDS patients was 35.1 months, but 18.4 months in the untreated group. Survival of all the AIDS patients was associated with factors as: treatment, age when AIDS diagnosis was made and route of HIV infection (P < 0.05). The risk of death among untreated patients was 5.78 times to the treated ones, but did not seem to relate to gender or nationality (P > 0.05). Survival of the treated group was associated with factors as gender, age when AIDS diagnosis was made, nationality, route of HIV infection, CD4(+) T cell count when AIDS diagnosis was made, CD4(+) T cell count at treatment baseline, anemia at the treatment baseline (P < 0.05). Survival of the untreated group was mainly associated with age when AIDS was diagnosed (P < 0.05) while other factors did not seem to be significantly related (P > 0.05). CONCLUSION: Antiretroviral therapy appeared an important factor that affecting the survival of AIDS patients, timely treatment and CD4(+) T cell count provided at the baseline for treatment, were two key factors that affecting the outcome of treatment. Our findings pointed out that tactic factors as: strengthening the detection, monitoring on CD4(+) T cell count, early diagnose and treatment, expanding the coverage of antiretroviral therapy, and appropriate timing for treatment etc., were important ways to enhance the effects of treatment, so as to reduce the mortality rate and prolong the time of survival. PMID- 26564627 TI - [Effect of treatment and HIV drug resistance of 81 cases of HCV/HIV co-infected individuals who had received AIDS second-line antiretroviral treatment in Henan province]. AB - OBJECTIVE: To understand the one-year effect of HCV/HIV co-infected patients who had received AIDS second-line antiretroviral treatment after failure virologically, on the first-line therapy. METHODS: HCV and HIV antibody positive patients who had experienced virological failure but received at least one-year AIDS first-line treatment, were recruited from May to October 2012 in Xincai, Queshan and Weishi of Henan province. 6-months and 12-months follow-up programs were carried out after the regimen had been changed to AIDS second-line antiretroviral treatment, CD4+ T lymphocyte count, HIV-1 virus load and HIV-1 drug resistance were performed. RESULTS: Eighty-one cases of eligible patients were selected and followed by an amelioration of CD4 median at 6-month and 12 month follow-up period. Data showed that the baseline, 6-months and 12-months CD4 medians were 266 cells/ul, 275 cells/ul and 299 cells/ul (chi2 = 8.214, P = 0.009). The ratio of HIV virus load suppression patients at 6-months and 12 months follow-up increased to 46.84% and 50.00%, respectively. Frequencies of HIV drug resistance also decreased at the baseline, 6-months and 12-months, with ratios as 66.67%, 26.58% and 27.63% (chi2 = 29.362, P = 0.000), respectively. Ratios of patients that holding NRTI and NNRTI drug resistance appeared coinstantaneous decrease at the baseline, 6-months and 12-months, as 51.85%, 18.99% and 17.11% (chi2 = 14.230, P = 0.005). At the baseline, the ratios of patients resisted to 3TC, ABC and FTC were all more than 50%, with AZT, D4T and DDI between 41%-44% while TDF appeared as 33.33%, then all of them declined to 12%-18% at the 6-month and 12-month follow-up periods. 65.43% of the patients resisted to both NVP and EFV but declined to 24%-27% at 6 months and 12 months. CONCLUSION: HCV/HIV co-infected patients experienced virological failure of AIDS first-line therapy were ameliorated after changing to use second-line antiretroviral treatment for 6-months, but did not show constant positive effect at the 12-month end point. PMID- 26564628 TI - [Cost-effectiveness of the HIV screening program carried out in Guangxi Zhuang Autonomous Region infectious disease special demonstration project areas]. AB - OBJECTIVE: To analyze the cost effectiveness of HIV screening project in three Guangxi infectious disease special demonstration project countries in 2013. METHODS: To calculate the funds used for the HIV screening project and to study the data on HIV/AIDS and HAART. A five-tree markov model was used to evaluate the quality adjusted life year (QALY) of this HIV screening project and to analyze the related cost effectiveness of the project. RESULTS: The cost of HIV screening in Guangxi infectious disease special demonstration project areas was 19.205 million Yuan and having identified 1 218 HIV/AIDS patients. The average costs for HIV/AIDS positive detection in three project countries were 14.562, 18.424 and 14.042 thousand Yuan per case. The QALYs gained from finding a HIV/AIDS case were 12.736, 8.523 and 8.321 on average, with the total number of QALYs gained from the project as 5 973.184, 3 613.752 and 2 704.325. The overall cost effectiveness ratio of the project was 1.562 thousand Yuan per QALY, and 1.143, 2.162 and 1.688 thousand Yuan per QALY in these three project countries. Project country "A" showed better cost effectiveness index than country B and C. CONCLUSION: The HIV screening project in Guangxi seemed relatively cost-effective but the average cost of HIV/AIDS positive detection was expensive. To strengthen HAART work for HIV/AIDS could improve the cost-effective of the project. PMID- 26564630 TI - [Association between polymorphisms of killer cell immunoglobulin-like receptor gene and the risk of essential hypertension: a case-control study]. AB - OBJECTIVE: To assess the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and the risk of hypertension in autoimmune mechanism. METHODS: We conducted a case-control study including 205 hypertensives and 205 controls matched with sex and age, from a community-based population. KIR genes of all subjects were genotyped by polymerase chain reaction with sequence specific primers (PCR-SSP). Conditional logistic regression model and generalized multifactor dimensionality reduction (GMDR) method were used to estimate the association among KIR gene polymorphisms and the risk of hypertension. RESULTS: The genotypic frequencies of KIRs were not significantly different between the hypertensives and the control groups (P > 0.05). Among all the models of GMDR concerning the association between interactions of KIR genes and essential hypertension, the testing accuracy of the interaction between KIR2DS2 and KIR2DS3 was the highest (55.13%), with cross-validation consistency as 10/10 (P = 0.054). Results from the conditional logistic regression showed that individuals with KIR2DS2+: KIR2DS3- were significantly associated with an increased risk on hypertension (OR = 2.555, 95% CI: 1.203-5.429, P = 0.015). However, individuals with KIR2DS2+: KIR2DS3+ were significantly associated with a reduced risk of hypertension (OR = 0.268, 95% CI: 0.088-0.815, P = 0.020). Individuals with KIR2DS2- KIR2DS3+ did not seem to be associated with the risk of hypertension (OR = 1.602, 95% CI: 0.785-3.266, P = 0.195), when compared to the KIR2DS2- KIR2DS3- group. Interactions between KIR2DS2 and KIR2DS3 were significantly associated with the risk of hypertension, after adjusted for BMI, smoking, drinking and family history of hypertension (OR = 0.065, 95% CI: 0.013-0.317, P = 0.001). CONCLUSION: Individuals with KIR2DS2 and no KIR2DS3 were associated with the increased risk of hypertension. KIR2DS2 that coexisted with KIR2DS3 were associated with the reduced risk of hypertension. Antagonism between KIR2DS2 and KIR2DS3 might serve as a protect factor for hypertension. PMID- 26564629 TI - [Analysis on HIV-1 genetics and threshold of drug resistance in Dehong prefecture of Yunnan province in 2013]. AB - OBJECTIVE: To study the HIV-1 genotypes and transmitted drug resistance (TDR) in Dehong prefecture of Yunnan province in 2013. METHODS: Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS), 54 plasma samples of recently reported HIV-infected individuals, aged between 16 and 25 years, were collected in Dehong prefecture from January to August 2013. Genotyping of partial pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype. Prevalent levels of HIV-1 drug resistance transmission were analyzed. RESULTS: Forty-eight plasma samples were successfully sequenced and analyzed. Among them, 45.8% were Chinese and the rest 54.2% were all Burmese. Based on pol sequences, identified HIV genotypes included subtype C (41.7%), URF (31.3%), CRF01_AE (12.5%), CRF07_BC (10.4%), CRF08_BC (2.1%) and subtype B (2.1%), C subtype appeared dominated in Chinese while URF was dominated in Burmese. One drug resistant mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in one sequence from Burmese. Based on the statistical method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was adjusted as < 5%. CONCLUSION: Diverse HIV-1 genotypes were found in this study, and the current HIV-1 drug resistant strains transmission was catalogued as at low prevalence level, in Dehong. To prevent the increase of the prevalence of transmitted HIV-1 drug resistance, standard treatment and scientific management for people living with HIV/AIDS should be strictly followed. Meanwhile, relevant surveillance, including drug resistance surveillance should also be performed among cross border migrant population. PMID- 26564631 TI - [A cohort study on dietary cholesterol intake and hypercholesterolemia among adults in 9 provinces and autonomous regions]. AB - OBJECTIVE: To explore the association between dietary cholesterol intake and hypercholesterolemia among Chinese adults. METHODS: In 2009, 4 244 adults aged 25 65 years old who participated in both 2004 and 2009 China Health and Nutrition Surveys, and with complete biochemical and dietary data were selected. Hypercholesterolemia were defined as with total cholesterol >= 6.22 mmol/L, according to 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Non-conditional logistic regression was used to investigate association between dietary cholesterol intake and hypercholesterolemia. RESULTS: The average total cholesterol was 4.9 mmol/L, with prevalence of hypercholesterolemia as 9.6%, in 2009. During 2004 to 2009, dietary cholesterol showed a dramatical increase, with lower intake groups the most. Males who consumed middle or lower dietary cholesterol in 2004 and high intake in 2009 had significantly higher risk of having hypercholesterolemia. However, similar findings did not appear in females. CONCLUSION: The associations between dietary cholesterol intake and hypercholesterolemia were different among Chinese males and females. Dramatic increase of dietary cholesterol intake was related to higher risk of hypercholesterolemia in males. PMID- 26564632 TI - [Epidemiological analysis on severe fever with thrombocytopenia syndrome under the national surveillance data from 2011 to 2014, China]. AB - OBJECTIVE: To analyze the epidemiological features and surveillance management programs on severe fever with thrombocytopenia syndrome (SFTS) in China from 2011 to 2014. METHODS: The analysis of epidemiological characteristics and surveillance management programs was based on the annual reporting data collected from the National Disease Reporting Information System while the description of cluster incidents was based on those reports collected from the Public Health Emergency Information Management System (PHEIMS). Association between age groups and fatality rate was tested under the Cochran-Armitage Trend Test. The difference of fatality rates between differing groups was analyzed, using the chi square test, with statistical significance on alpha = 0.05. RESULTS: Between 2011 and 2014, 5 352 suspected, probable and lab-confirmed cases of SFTS were reported in 23 provinces, of which 16 provinces reported 2 750 lab-confirmed cases with a fatality of 7.9%, accounting for 51.4% of all the cases, nation-wide. Henan, Shandong, Hubei, Anhui, Liaoning, Zhejiang and Jiangsu reported 99.3% of those lab-confirmed cases. The period between April and October appeared the epidemic season, with its peak from May to July. Most cases were farmers, accounted for 88.3% of the lab-confirmed cases. People at the age between 50-74 occupied 67.6% of all the cases. Fatality of the disease continually increased from 3.7% in the age group 40-44 to 13.5% in the age group older than 80. Fatality rates appeared statistically different between the groups with or without misdiagnosis, with OR as 3.06 (95% CI: 1.61-5.90). Secondary cases of the cluster incidents were most likely to result from contacting the blood of the index cases. CONCLUSION: Number of reported SFTS cases showed a rising trend in China. Henan, Hubei, Anhui, Shandong and Liaoning provinces appeared at high risk of the disease. Geographical distribution of the SFTS cases' seemed highly sporadic, with May to July being the peak season. Farmers and elderly were considered as high risk population. Occasionally, cluster incidents might be seen, as the result of contacting the blood of cases or corpses. Being at older age and misdiagnosis seemed to be risk factors for fatality. PMID- 26564633 TI - [Study on illegal driving behavior and vehicle road traffic injury in China from 2006 to 2010]. AB - OBJECTIVE: To study the characteristics and trend of illegal driving behavior in China to provide evidence for related policy enforcement. METHODS: Using indices as death rate of ten thousand vehicle, death rate per 100 000 population, thousands of road mileage, degree of motorization and death ratio etc. to analyze the current situation, characteristics of illegal vehicle driving behavior related to road traffic injuries, in China. RESULTS: From 2006 to 2010, death ratio on vehicle road traffic injuries related to the top five illegal driving behaviors were as follows: speeding (from 0.33 down to 0.17), on refuse to give way to others (from 0.26 to 0.14), on driving without license (from 0.21 to 0.08), on illegal driving encroachment (from 0.17 to 0.04) and on reverse driving (from 0.11 to 0.07). Death rates related to vehicle road traffic injuries on drunk driving or fatigue driving were 0.04 in 2010 and 0.02 in 2010, respectively. CONCLUSION: Despite the fact that the number of vehicle road traffic injuries appeared a declining trend, the severity was increasing. Illegal driving behavior was still prevalent in China. PMID- 26564634 TI - [Information obtained through Internet-based media surveillance regarding domestic public health emergencies in 2013]. AB - OBJECTIVE: To analyze the information obtained through Internet-based media surveillance in 2013 on domestic public health emergencies and to compare with the related data reported through Chinese Public Health Emergency Management Information System (PHEMIS), and to study the role of Internet-based Media Surveillance Program (IBMSP) in the detection of public health emergencies. METHODS: A descriptive analysis was conducted based on the database of the information on domestic public health emergencies. Information was obtained through the Internet-based media surveillance in 2013. RESULTS: A total of 752 pieces of information regarding domestic public health emergencies in 31 provinces were obtained, through the IBMSP, run by the China CDC in 2013. 53.46% of all the information were categorized as initial ones on public health emergency while another 22.07% were considered as updated ones. 41.62% of the information were related to infectious diseases with another 24.73% to food poisoning. 27.53% of the information were from official websites of governments and professional organizations, with the rest 72.47% were from media. As for corresponding public health emergencies, 41.79% were food poisoning and 18.66% were infectious diseases. 22.39% of them occurred in schools, 18.16% in other organizations and 16.92% in households. 28.86% were reported through Chinese PHEMIS. For the 116 public health emergencies that both related to information obtained through Internet-based media surveillance in 2013 and reported through PHEMIS, the median days of interval between illness onset of the first case as well as reported by media, interval between onset of the first case as well as reported through PHEMIS, were 2.5 days and 2.0 days respectively. 19.83% of the emergencies were first reported by media than through PHEMIS. CONCLUSION: Internet-based media surveillance programs had become an important way to detect public health emergencies and could serve as the supplement to the classic surveillance programs on public health emergencies. PMID- 26564635 TI - [Relationship between self-rated filial piety and depressive symptoms among the elderly]. AB - OBJECTIVE: To examine the association between self-rated filial piety and depression among the elderly, in order to provide evidence for improving the intervention programs on mental health in the elderly. METHODS: Descriptive, correlative and multiple logistic regression models were used to analyze the elderly aged 60 years or over relationship between self-rated filial piety and depressive symptoms. Source of data was from the 2010 Sample Survey of the Aged Population in Urban/Rural China (n = 18 234). RESULTS: Twenty-two point five zero and 1.66% of the respondents reported having had depression with poor self-rated filial piety. Findings from multiple logistic regression showed that poor self rated filial piety was associated with higher risk of depression when comparing to those under 'so-so self-rated filial piety' (OR = 1.88, 95% CI: 1.71-2.07) or good self-rated filial piety (OR = 3.15, 95% CI: 2.41-4.12) among the elderly, after adjusting for factors related to socio-demographic and familiar characteristics. CONCLUSION: Poor self-rated filial piety was associated with depression among the elderly. Programs including support to the elderly and reinforcing publicity on filial piety plus intervention for the elderly with poor self-rated filial piety should be implemented to protect the mental health in the elderly. PMID- 26564636 TI - [Analysis on the imported measles cases in Beijing, 2014]. AB - OBJECTIVE: To analyze the imported measles cases who came to Beijing seeking for better medical services and to explore the feasible strategies for prevention and control of the situation. METHODS: Descriptive analysis was conducted for all the measles cases noted from the Measles Surveillance System, between January 1, 2014 and December 31, 2014. RESULTS: 3 328 measles cases were reported in Beijing, including 2 397 (2 397/3 328, 72.0%) native residents and 931 (931/3 328, 28.0%) came from other provinces. Peak of the imported cases appeared earlier than those native cases, with 934 cases (934/2 397, 39.0%) having had hospital exposure 7-21 days prior to the onset of the disease. Majority of the imported were children, including 718 of them (718/931, 77.1%) under the age of 15. Most cases were reported from 3 infectious disease hospitals (567/1 156 person-time, 49.0%) and 2 children's hospitals (445/1 156 person-time, 38.5%). Original addresses of the imported cases distributed in 24 provinces, with 705 of them (705/931, 75.7%) coming from Beijing's neighboring province (Hebei). Clinic symptoms with epidemiological information were analyzed on 712 cases. 704 cases (704/712, 98.9%) presented rash at home town while another 621 cases (621/712, 87.2%) developed rash 4 days after arriving in Beijing and were still in the infectious period. CONCLUSION: There was a big amount of imported measles cases in Beijing that called for the elimination of the disease in a urgent phase. It is necessary to timely develop and conduct targeted prevention and control measures on the disease in Beijing. PMID- 26564637 TI - [Spatial clustering of hand-foot-mouth disease in Gansu, 2012]. AB - OBJECTIVE: The purpose of this study was to explore the spatial distribution and spatial clustering of hand-foot-mouth disease (HFMD) in Gansu, 2012. METHODS: Spatial autocorrelation and Spatial scanning analysis were used to conduct spatial statistical analyses for the HFMD at the county/district level. RESULTS: HFMD cases did not show a random distribution but with significant spatial aggregation. When Local Autocorrelation analysis was applied at the county/district level, with nine hot spot areas as Jiayuguan, Yumen, Dunhuang, Jinta, Suzhou, Chengguan, Anning, Xigu and Gaolan, were discovered. Four statistically significant HFMD clusters were identified by spatial scan statistics. CONCLUSION: HFMD was noticed geographically clustered in Gansu in 2012. Results from this study indicated that the spatial autocorrelation and spatial scanning analysis could effectively detect the areas which presenting significant clusters. Cluster Detection System (CDS) could provide evidence for the development of an effective measure concerning the prevention and control of HFMD. PMID- 26564638 TI - [Trends on the changing prevalence in patients with early syphilis and HIV infection among men who having sex with men in Nanjing, from 2008 to 2013]. AB - OBJECTIVE: To observe the trends on prevalence of early syphilis and HIV infection among men who had sex with men in the last six years from a HIV/AIDS counseling and testing clinic in Nanjing, and to develop relative strategies. METHODS: Men who have sex with men involved in AIDS/HIV and syphilis voluntary counseling and testing services were recruited and investigated from 2008 to 2013 in this clinic. Clients whose syphilis serologic test showed positive were determined the diagnosis by physician within the referral network from sexually transmitted diseases clinics. Demographic information on early syphilis, HIV infection or co-infection with HIV and early syphilis was described while related epidemic trend analysis was performed. RESULTS: The annual numbers of men having sex with men under survey were 1 004 in 2008, 1 218 in 2009, 1 236 in 2010, 748 in 2011, 1 019 in 2012 and 1 420 in 2013. The prevalence rates of early syphilis appeared to be: 2.19% in 2008, 2.71% in 2009, 2.43% in 2010, 1.74% in 2011, 3.04% in 2012 and 2.32% in 2013, with the trend as: P > 0.05. The prevalence rates of HIV infection were 1.29% in 2008, 2.63% in 2009, 5.42% in 2010, 8.82% in 2011, 11.97% in 2012 and 10.42% in 2013, with trend as: P < 0.01. The prevalence rates of early syphilis with HIV infection increased from 0.20% in 2008 to 1.06% in 2013 (trend: P < 0.01). The proportion of HIV co-infection among men having sex with men with early syphilis infection, increased from 9.09% in 2008 to 45.45% in 2013, with trend: P < 0.01. CONCLUSION: Early syphilis infection among men who having sex with men showed a stable trend but the number of HIV and co-infections with early syphilis and HIV increased rapidly in the last six years in Nanjing. Continued intervention strategies should target on men who have sex with men to slow down the epidemic of syphilis and HIV infection. PMID- 26564639 TI - [An outbreak of foot pain syndrome among students from a senior high school in Foshan, Guangdong province, 2014]. AB - OBJECTIVE: To identify the cause of an outbreak of foot pain syndrome among students from a senior high school in Foshan. METHODS: We defined a suspect case as onset of foot pain/numbness with unknown reason among students and teachers in a school of Foshan city, from February 10 to March 16, 2014. A suspect case was noticed as having both food pain and numbness. All the cases were searched through reviewing medical records in the nearby hospitals and school's clinic, also the records of absenteeism in school. Clinical information was collected from all the students, using a standardized questionnaire. Daily temperature was collected from all the students, between January 1 and March 31, 2014. A 1 : 2 individual matched case-control study was conducted to identify related risk factors on this epidemic. We interviewed all the cases and controls on their diet, physical activities and measures used for warming. RESULTS: A total of 407 case-students were identified, with an attack rate (AR) as 26.5%. The AR was 37.3% in girls, compared to 12.9% in boys. The difference was statistically significant (chi2 = 115.1, P < 0.01). Boarding students had a higher AR (31.8%) than the commuting students (16.2%). The difference was statistically significant (chi2 = 43.2, P < 0.01). In girls, boarding students had higher AR (46.1%) than those commuting students (18.5%). The difference was statistically significant (chi2 = 61.4, P < 0.01). No statistically significant difference was found between boarding or commuting students in boys. Outdoor temperature was coming down from 23 degrees C on February 6 to 6 degrees C on February 13, but gradually rose to 23 degrees C on February 28. There was a positive relationship (r = 0.65, P = 0.002) noticed between daily maximum temperature and the number of cases during February 13-28. Results from this case-control study showed that factors as lacking physical activities (OR = 2.8, 95% CI: 1.5-5.6), feeling cold in bed (OR = 3.0, 95% CI: 1.3-7.0) and having experienced similar symptoms (OR = 3.4, 95% CI: 1.1-11.0) could increase the risk of this disease. CONCLUSION: This outbreak was possibly caused by the abrupt fluctuation of temperature within a short period. PMID- 26564640 TI - [Research on the association between U2-dependent spliceosome gene and hepatocellular cancer]. AB - OBJECTIVE: To determine the association between U2-dependent spliceosome related 8 key genes and hepatocellular cancer (HCC). METHODS: A two-stage case-control study was conducted. Twenty-two candidate tag single nucleotide polymorphisms (tagSNPs) were genotyped by TaqMan Openarray assay in a screened population that living in Central China (378 HCC incident cases and 461 controls). Frequencies of 4 SNPs (rs2074733, rs9608886, rs7288947 and rs5994293) showed significant difference between cases and controls in the screened population and then genotyped by TaqMan real-time polymerase chain reaction in the validation Chinese Han population from Beijing (428 cases and 647 controls). RESULTS: The rs5994293 in SF3A1 gene showed a significant association with HCC in both screened population and combined population. Subjects with G allele had a lower risk of HCC, compared to those with the TT genotype. OR appeared to be 0.70 (95% CI: 0.58 0.84, false discovery rate adjusted P = 0.000 5) for the combined population. An additive interaction between smoking, drinking alcohol and rs5994293 TT was observed in HBsAg negative subjects of the combined populations. CONCLUSION: Our results showed an association existing between SF3A1 rs5994293 and HCC. These findings should be confirmed by further independently large-scale population studies and functional analysis. PMID- 26564641 TI - [Phenotype and genotype of antimicrobial resistance on nasal Staphylococcus aureus isolates from healthy people]. AB - OBJECTIVE: To investigate the antimicrobial susceptibility and molecular nature related to the resistance on macrolides from nasal Staphylococcus (S.) aureus isolates among healthy people. METHODS: A total of 100 S. aureus isolates collected from 2009 to 2011 were tested for antimicrobial susceptibility by E test. Double disc test (D-test) was used to detect the inducible clindamycin resistance. All S. aureus isolates were characterized by spa typing. Macrolides resistance genes were detected and compared with isolates that were collected clinically or from the livestock. RESULTS: High resistance rates on erythromycin or clindamycin was noticed, with 52% and 27%, respectively. Inducible clindamycin resistance was identified in 29 of the 100 (29%) isolates. In total, the 100 isolates were assigned to 35 spa types. The most common spa types were found to be t189, t571, t002, t796, t437, t034 and t701, that accounted for 51.0% of all the isolates. erm (C) (57.7%) and erm (B) (34.6%) were found as the dominant genes in 52 S. aureus isolates from healthy people. On the other hand, erm (A) and erm (C) were identified in 95.0% S. aureus isolates from patients and all the livestock, respectively. CONCLUSION: erm (C) and erm (B) carrying S. aureus strains were circulating in healthy people and these genes were distributed in different S. aureus clones. PMID- 26564642 TI - [Relationship between pre-pregnant body mass index, maternal weight gain and small for gestational age]. AB - OBJECTIVE: To investigate the relationship between maternal pre-pregnancy body mass index, weight gain during pregnancy and small for gestational age (SGA) birth so as to provide evidence for the development of comprehensive prevention programs on SGA birth. METHODS: Between March, 2012 and July, 2014, 4 754 pregnant women were asked to fill in the questionnaires which were collected from the First Affiliated Hospital of Shanxi Medical University. Data related to general demographic characteristics, pregnancy and health status of those pregnant women was collected and maternal pre-pregnancy body mass index and maternal weight gain were calculated. Subjects were divided into different groups before the effect of maternal pre-pregnancy body mass index and weight gain during pregnancy on SGA birth were estimated. RESULTS: The overall incidence of SGA birth was 9.26% (440/4 754). Proportions of SGA birth from pre-pregnant, underweight group, normal weight group, overweight and obese groups were 9.85%, 8.54% and 9.45%, respectively. Results from multi-factor logistic regression analyses showed that after adjusting the confounding factors as age, history on pregnancies etc., women with high pre-pregnancy BMI showed a lower incidence of SGA than those under normal pre-pregnancy BMI (OR = 0.714, 95% CI: 0.535-0.953). Different weight gains during pregnancy were statistically significant (chi(2) = 8.811, P = 0.012). Incidence of SGA birth that was below the recommended range in the 2009 Institute of Medicine Guidelines (12.20%) was higher than those within (9.23%) or beyond (8.45%) the recommended range. Results from the multi-factor logistic regression analyses showed that, after adjusting the confounding factors as age, pregnancy history etc., factor as weight gain below the recommended level could increase the risk of SGA (OR = 1.999, 95% CI: 1.487-2.685). In the underweight, normal weight, overweight or obese groups, with weight gain during pregnancy below the range, the incidence of SGA showed an increase (OR = 2.558, 95% CI: 1.313-4.981, OR = 1.804, 95% CI: 1.258-2.587, OR = 3.108, 95% CI: 1.237 7.811). There was no interaction of addictive or multiplicative models between these two factors under 'interaction analysis'. CONCLUSION: Women with high pre pregnancy BMI presented a lower incidence of SGA than those within the normal range. Insufficient weight gain during pregnancy could increase the risk of SGA delivery. These findings called for attention to be paid to the gestational weight gain, in order to decrease the risk of SGA. PMID- 26564643 TI - [Effect of maximum blood pressure when discharged from the hospital on the prognosis among patients with acute ischemic stroke]. AB - OBJECTIVE: To investigate the relationship between maximum blood pressure and the prognosis after discharged from the hospital, among patients with ischemic stroke. METHODS: A cohort study was conducted which including 471 cases of ischemic stroke patients that were collected from February 2014 to December 2014 at the Second Affiliated Hospital of Harbin Medical University. Values of everyday blood pressure were measured on each patient at the first six days after admitted to the hospital. Maximum blood pressure value of the 6 days was taken as an indicator of the blood pressure levels. The ability on daily living was measured by the modified Rankin score (mRs). Data were analyzed by Chi-square test, t test and multivariate logistic regression analysis. RESULTS: Confounding factors would include age, gender, culture, physical activity, income, smoking, alcohol, hypertension, diabetes, coronary heart disease, stroke history, hospitalization mRs, lipid parameters, homocysteine and blood sugar and were adjusted. Results from multivariate logistic regression analysis showed that the maximum SBP was associated with adverse outcomes. Compared with 140-159 mmHg for SBP, OR (95% CI) was 2.51 (1.30-4.85) for 160-179 mmHg, OR (95% CI) was 2.68 (1.27-5.65) for those pressure levels higher than 180 mmHg, after multiple factors were adjusted. Compared with 90-99 mmHg for DBP, OR (95% CI) was 1.92 (1.00-3.67) for 100-109 mmHg, OR (95% CI) was 2.78 (1.35-5.69) for the ones higher than 110 mmHg. CONCLUSION: Maximum blood pressure during hospitalization might be associated with adverse outcome of ischemic stroke patients. PMID- 26564644 TI - [Distribution of beta3-adrenergic receptors gene polymorphisms and its association with serum lipid in Han and Uighur populations in Xinjiang]. AB - OBJECTIVE: To investigate the distribution of beta3-adrenergic receptors (ADRbeta3) gene polymorphisms (rs2298423 and rs6986132) and its association with serum lipid in Han and Uighur populations in Xinjiang. METHODS: Genotypes of the ADR beta 3 gene were detected in 362 Uighur and 653 Han healthy individuals who were randomly selected in Xinjiang by real-time PCR (TaqMan) method. RESULTS: 1) Frequencies of TT, GT and GG genotypes of the rs2298423 locus were 76.5%, 22.1% and 1.4% in the Uighurs but 74.7%, 23.3% and 2.0% in the Hans. There was no significant difference noticed in distribution of genotypes between the two populations (P = 0.695). 2) Frequencies of GG, AG and AA genotypes of the rs6986132 locus were 81.5%, 16.6% and 1.9% in Uighurs but 59.6%, 33.7% and 6.7% in Hans. There was significant difference noticed in the distribution of genotypes between the two populations (P < 0.001). 3) Total cholesterol and low density lipoprotein cholesterol levels were significantly higher in GG or GT genotypes than in the TT genotype carriers of rs2298423 in the Uighur individuals (P < 0.01), but not in the Han population. Serum lipid level that including total cholesterol (TC), low density lipoproteins cholesterol (LDL-C), triglyceride and high density lipoproteins cholesterol did not show significant differences in the distribution of rs6986132 genotypes between the two populations (P > 0.05). After adjusting for factors as gender, age, height, weight, waist circumference, blood urea nitrogen, creatin, glucose, triglyceride, smoking, drinking, results from the logistic regression analyses revealed that those individuals who were carrying GG or GT genotype of rs2298423 were expected to face an increased risk for total cholesterol and low density lipoprotein cholesterol level than those individuals that carrying TT genotype in Uighur populations (OR = 3.140, 95% CI: 1.270-7.764, P = 0.013 in TC level; OR = 3.818, 95% CI: 1.761-8.280, P = 0.001 in LDL-C level). 4) The T-G haplotype appeared more frequent in the Uighurs while the T-A haplotype was more commonly seen in the Han population, respectively (both P < 0.001). CONCLUSION: The mutational frequencies of the tagging SNPs in rs2298423 and rs6986132 loci of the ADRbeta 3 gene presented obvious differences between Han and Uighur populations of Xinjiang. G allele carriers of rs2298423 seemed to face an increased risk for TC and LDL-C level in the Uighur populations in Xinjiang. PMID- 26564645 TI - [Minimal-Intervention on smoking cessation: a Meta-analysis]. AB - OBJECTIVE: To systematically evaluate the effectiveness of Minimal Smoking Cessation Intervention Program (MSCIP) and to provide theoretical basis for the feasibility of implementation in China. METHODS: Systematically, we searched data from studies published between January, 2000 and September, 2014 on the database that including Cochrane Library, Medline, EMbase, CNKI, Wanfang, Vip, etc. Studies related to MSCIP were designed by random controlled trials. Meta analysis was performed by Revman 5.1. RESULTS: Nine studies were included, with the Random Effect Model Relative Risk as 1.57 (1.01-2.44), which indicated that the probability of being tobacco abstinent had increased by 57% in the treating group than in the control group. Participants who developed other diseases, being pregnant or the time of receiving intervention messages <= 10 minutes, were more likely to quit the program. There were no significant statistically differences noticed between the different subgroups. CONCLUSION: Minimal smoking cessation intervention increased cessation rates, RCTs with a larger sample size are needed to draw the related conclusions. PMID- 26564646 TI - Adult perceptions of dental fluorosis and select dental conditions-an Asian perspective. AB - OBJECTIVE: To compare lay people's perceptions with regard to various levels of dental fluorosis and select dental defects versus normal dentition. METHODS: Adults rated digitally created photographs made showing lips (without retraction) and teeth depicting the following conditions: no apparent aesthetic defects (normal, Thylstrup- Fejerskov score 0 - TF0), 6 levels of fluorosis (TF1-6), carious lesions (two cavitated and one noncavitated), malocclusions (Class II, Class III, anterior open bite and greater spacing), extrinsic staining and an incisal chip. The photographs were displayed on colour-calibrated iPads(TM) . Participants used a self-administered questionnaire to rate their perceptions on (Item 1) how normal teeth were, (Item 2) how attractive the teeth were, (Item 3) need to seek correction of teeth, (Item 4) how well the person took care of their teeth and (Item 5) whether the person was born like this. Data from Item 5 were excluded due to low reliability. RESULTS: Ratings for Item 1 showed that TF1-4 was similar or significantly better than TF0. For Item 2, TF1 and TF4 were significantly better than TF0, with TF2 and TF3 being similar. For Item 3, there was significantly lower need to seek correction with TF2 and TF4 versus TF0, whereas TF1 and TF3 were similar to TF0. TF5 and TF6 were rated significantly lower than TF0 for Item 1 and Item 2, and significantly higher rating for Item 3 (need to seek correction). Ratings for Item 4 were similar, with TF1, TF2 and TF4 being rated significantly higher than TF0, and TF5 and TF6 being rated lower. Cavitated caries and staining were generally perceived as being significantly less favourable than TF6, with higher need to seek correction as well. Noncavitated carious lesion and incisal chip were rated similar to TF0. Cavitated carious lesions were rated aesthetically similar or significantly worse than TF0 and TF6. CONCLUSIONS: Severe fluorosis (TF5 and 6) was perceived to be less aesthetically pleasing and received higher ratings for need to seek correction than normal teeth. Mild-to-moderate fluorosis (TF1-4) showed similar or better aesthetic perceptions and similar or lower need to seek correction, when compared to normal teeth (TF0). Easily visible cavitated dental caries was rated worse than teeth with severe fluorosis (TF6) and normal teeth (TF0). PMID- 26564647 TI - Pioneers and pit crews. PMID- 26564649 TI - Add to cart? PMID- 26564651 TI - Surprised by photos. PMID- 26564652 TI - Relationship with pharmaceutical companies. PMID- 26564653 TI - Rourke Baby Record 2014: Evidence-based tool for the health of infants and children from birth to age 5. AB - OBJECTIVE: To update the 2011 edition of the Rourke Baby Record (RBR) by reviewing current best evidence on health supervision of infants and children from birth to 5 years of age. QUALITY OF EVIDENCE: The quality of evidence was rated with the former (until 2006) Canadian Task Force on Preventive Health Care classification system and GRADE (grading of recommendations, assessment, development, and evaluation) approach. MAIN MESSAGE: New evidence has been incorporated into the 2014 RBR recommendations related to growth monitoring, nutrition, education and advice, development, physical examination, and immunization. Growth is monitored with the World Health Organization growth charts that were revised in 2014. Infants' introduction to solid foods should be based on infant readiness and include iron-containing food products. Delaying introduction to common food allergens is not currently recommended to prevent food allergies. At 12 months of age, use of an open cup instead of a sippy cup should be promoted. The education and advice section counsels on injuries from unstable furniture and on the use of rear-facing car seats until age 2, and also includes information on healthy sleep habits, prevention of child maltreatment, family healthy active living and sedentary behaviour, and oral health. The education and advice section has also added a new environmental health category to account for the effects of environmental hazards on child health. The RBR uses broad developmental surveillance to recognize children who might be at risk of developmental delays. Verifying tongue mobility and patency of the anus is included in the physical examination during the first well-baby visit. The 2014 RBR also provides updates regarding the measles-mumps-rubella, live attenuated influenza, and human papillomavirus vaccines. CONCLUSION: The 2014 RBR is the most recent update of a longstanding evidence-based, practical knowledge translation tool with related Web-based resources to be used by both health care professionals and parents for preventive health care during early childhood. The 2014 RBR is endorsed by the Canadian Paediatric Society, the College of Family Physicians of Canada, and the Dietitians of Canada. National and Ontario versions of the RBR are available in English and French. PMID- 26564654 TI - Diagnosing hypertension: Evidence supporting the 2015 recommendations of the Canadian Hypertension Education Program. AB - OBJECTIVE: To highlight the 2015 Canadian Hypertension Education Program (CHEP) recommendations for the diagnosis and assessment of hypertension. QUALITY OF EVIDENCE: A systematic search was performed current to August 2014 by a Cochrane Collaboration librarian using the MEDLINE and PubMed databases. The search results were critically appraised by the CHEP subcommittee on blood pressure (BP) measurement and diagnosis, and evidence-based recommendations were presented to the CHEP Central Review Committee for independent review and grading. Finally, the findings and recommendations were presented to the Recommendations Task Force for discussion, debate, approval, and voting. The main recommendations are based on level II evidence. MAIN MESSAGE: Based on the most recent evidence, CHEP has made 4 recommendations in 2 broad categories for 2015 to improve BP measurement and the way hypertension is diagnosed. A strong recommendation is made to use electronic BP measurement in the office setting to replace auscultatory BP measurement. For patients with elevated office readings, CHEP is recommending early use of out-of-office BP measurement, preferably ambulatory BP measurement, in order to identify early in the process those patients with white-coat hypertension. CONCLUSION: Improvements in diagnostic accuracy are critical to optimizing hypertension management in Canada. The annual updates provided by CHEP ensure that practitioners have up-to-date evidence-based information to inform practice. PMID- 26564655 TI - Biliary atresia. PMID- 26564656 TI - The skinny on BMI and mortality. PMID- 26564657 TI - Low-dose acetylsalicylic acid for primary prevention of cardiovascular disease: Do not misinterpret the recommendations. PMID- 26564659 TI - Treatment and prevention of traveler's diarrhea. PMID- 26564661 TI - Gloomy in Glenburn. PMID- 26564662 TI - Jennifer Whelan MB BCh BAO CCFP. PMID- 26564663 TI - A perfect family medicine storm. PMID- 26564666 TI - Should CPD for opioid prescribing be mandatory? PMID- 26564667 TI - Design and development of an ethnically-diverse imaging informatics-based eFolder system for multiple sclerosis patients. AB - PURPOSE: MRI has been used to identify multiple sclerosis (MS) lesions in brain and spinal cord visually. Integrating patient information into an electronic patient record system has become key for modern patient care in medicine in recent years. Clinically, it is also necessary to track patients' progress in longitudinal studies, in order to provide comprehensive understanding of disease progression and response to treatment. As the amount of required data increases, there exists a need for an efficient systematic solution to store and analyze MS patient data, disease profiles, and disease tracking for both clinical and research purposes. METHOD: An imaging informatics based system, called MS eFolder, has been developed as an integrated patient record system for data storage and analysis of MS patients. The eFolder system, with a DICOM-based database, includes a module for lesion contouring by radiologists, a MS lesion quantification tool to quantify MS lesion volume in 3D, brain parenchyma fraction analysis, and provide quantitative analysis and tracking of volume changes in longitudinal studies. Patient data, including MR images, have been collected retrospectively at University of Southern California Medical Center (USC) and Los Angeles County Hospital (LAC). The MS eFolder utilizes web-based components, such as browser-based graphical user interface (GUI) and web-based database. The eFolder database stores patient clinical data (demographics, MS disease history, family history, etc.), MR imaging-related data found in DICOM headers, and lesion quantification results. Lesion quantification results are derived from radiologists' contours on brain MRI studies and quantified into 3-dimensional volumes and locations. Quantified results of white matter lesions are integrated into a structured report based on DICOM-SR protocol and templates. The user interface displays patient clinical information, original MR images, and viewing structured reports of quantified results. The GUI also includes a data mining tool to handle unique search queries for MS. System workflow and dataflow steps has been designed based on the IHE post-processing workflow profile, including workflow process tracking, MS lesion contouring and quantification of MR images at a post-processing workstation, and storage of quantitative results as DICOM-SR in DICOM-based storage system. The web-based GUI is designed to display zero footprint DICOM web-accessible data objects (WADO) and the SR objects. SUMMARY: The MS eFolder system has been designed and developed as an integrated data storage and mining solution in both clinical and research environments, while providing unique features, such as quantitative lesion analysis and disease tracking over a longitudinal study. A comprehensive image and clinical data integrated database provided by MS eFolder provides a platform for treatment assessment, outcomes analysis and decision-support. The proposed system serves as a platform for future quantitative analysis derived automatically from CAD algorithms that can also be integrated within the system for individual disease tracking and future MS-related research. Ultimately the eFolder provides a decision-support infrastructure that can eventually be used as add-on value to the overall electronic medical record. PMID- 26564668 TI - Symmetry in early response to intravitreal ranibizumab in bilateral diabetic macular oedema. AB - PURPOSE: To study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). METHODS: The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) >=5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. RESULTS: The VA improved significantly after ranibizumab treatment in both eyes (p < 0.01). A statistically significant positive correlation was found for the functional response to ranibizumab between the FE and the SE (R(2) = 0.26, p = 0.03). The mean CMT decreased significantly in both eyes (p < 0.01). A strong positive correlation was observed between the anatomical response to ranibizumab in the FE and the SE (R(2) = 0.37, p = 0.01). Symmetric favourable anatomical and functional responses were observed in 13 patients (72%). In two additional patients, an asymmetric functional response was observed despite a decrease in retinal thickness in both eyes. CONCLUSION: Symmetric anatomical and functional responses were observed in 72% of patients with DME after three initial IVR in each eye. This finding could be of clinical interest in the decision to treat the fellow eye, in a disease where a bilateral involvement is frequent. PMID- 26564670 TI - Focus on Our Tax Code and Global Activities. PMID- 26564671 TI - Military Research ColorDx and Printed Color Vision Tests. AB - PURPOSE: To determine the equivalence of the ColorDx Military Research version (mColorDx) test and three printed pseudoisochromatic tests (HRR, Ishihara, and PIPIC) for color vision testing. METHODS: Participating in the study were 75 color-normals and 47 subjects with red-green color vision defects. Color vision was classified by an anomaloscope. The HRR (4(th) edition), Ishihara 38-plate edition, and PIPIC tests are printed color vision tests, whereas mColorDx test figures were displayed on a calibrated computer desktop monitor. All tests were repeated in about 1 wk. RESULTS: The kappa level of agreement (kappa) values with the anomaloscope for screening for each test was 0.96 or greater. The values were statistically identical. Specificity for each test was at least 0.99 and sensitivity was at least 0.95. The repeatability of the screening sections for all tests was very good with kappa values greater than 0.95. Deutans tended to miss the tritan screening plates on the HRR and mColorDx tests. The Spearman rank correlation coefficients between the severity of the defect and anomaloscope range was moderate with r = 0.45 for the mColorDx and r = 0.6 for the HRR. Both the mColorDx and HRR had perfect agreement with the anomaloscope in classifying the defects as either protan or deutan. CONCLUSION: The validity of the four tests for color vision screening was statistically identical; however, the HRR may be preferred because it had the highest sensitivity of 0.99, a specificity of 1.0, and a reasonable correlation between the severity rating of the defect and the anomaloscope range. PMID- 26564672 TI - Overactive Performance Monitoring Resulting from Chronic Exposure to High Altitude. AB - INTRODUCTION: The neural mechanisms underlying the influence of chronic exposure to high altitude on performance monitoring are not clear. We investigated performance monitoring in the context of chronic exposure to high altitude. METHODS: A go/no-go task was used to obtain event-related potentials (ERP). The error-related negativity (ERN), correct-related negativity (CRN), and error positivity (Pe) components were measured in high-altitude and low-altitude groups. The high-altitude group had lived at high altitude for 3 yr, but were born and raised at low altitude, whereas the low-altitude group had lived at low altitude only. RESULTS: The ERN amplitudes were larger in the high-altitude group compared with the low-altitude group (-14.00 +/- 8.34 MUV vs. -7.82 +/- 8.42 MUV, respectively). Moreover, the CRN amplitudes were larger in the high-altitude group (3.51 +/- 4.50 MUV vs. 8.65 +/- 3.23 MUV, respectively). Group differences were not significant for the Pe component. DISCUSSION: These results suggest that chronic exposure to high altitude can cause overactive performance monitoring in the high-altitude group, but the later stage of error monitoring was not influenced. PMID- 26564673 TI - Simulated Spaceflight Operations Under Sleep Deprivation and Confinement. AB - INTRODUCTION: This study investigated how operation complexity and type affect Chinese individuals' performance of simulated spaceflight operations under conditions of sleep deprivation and confinement (SDC). METHODS: There were 20 male volunteers who were randomly divided into 2 groups: the SDC group (N = 8) and the control group (N = 12). During the 72-h experimental period, the volunteers were asked to perform 11 computerized spaceflight emergency procedures, varying in operation complexity and type, three times at the 9(th), 33(rd), and 57(th) hours, respectively. Operation times and errors of each spaceflight emergency procedure were recorded. Three complexity levels (i.e., low complexity, high complexity, and combined complexity) and three operation types (i.e., two-way judgment, manual operation, and mixed operation) were identified according to an operation complexity measure and an engineering definition. RESULTS: Mixed model ANOVAs indicated that performance of the three complex operations and three operation types were negatively affected by SDC. Moreover, the results showed that the operation time of the manual operation (10.67 +/- 1.706 at the 9th hour, 13.94 +/- 4.261 at the 33rd hour) and mixed operation (4.88 +/- 0.247 at the 9th hour, 5.15 +/- 1.308 at the 57th [corrected] hour) increased significantly with the increase of waking time. It was also shown that the high complexity operation and manual operation got less variation in operation time compared with low complexity and two-way judgment, respectively. CONCLUSIONS: The result indicated that the task assignment with high complexity requiring cognition could be a useful way to counteract the effect of SDC. It was also implied that psychomotor abilities were more easily affected by SDC than perception and judgment. PMID- 26564674 TI - Physical Fitness and Dehydration Influences on the Cardiac Autonomic Control of Fighter Pilots. AB - BACKGROUND: Physical fitness and dehydration are factors that may influence cardiac autonomic control. We aimed to verify the influence of these factors on cardiac autonomic control before, during, and after a flight. METHODS: At the same time of day, 11 healthy fighter pilots recorded several 1-h bouts of heart rate (HR) activity during a non- (control) and a training flight day. Autonomic control of HR was examined via time domain and non-linear heart rate variability (HRV) analyses. The level of dehydration during the flight was evaluated by changes in hematocrit, while aerobic capacity, muscular strength, and body fatness were the physical fitness components evaluated. RESULTS: The flight induced a significant reduction in most parameters of HRV during flight time when compared to the control day. However, no differences were found between the days before the flight, while the root mean square of successive differences (RMSSD) of HR was the only parameter significantly reduced (11.05 +/- 7.7%) after the flight. Significant correlations were observed between the sample entropy of HR during flight and aerobic capacity (r = 0.777) and body fatness (r = -0.617). Correlations between dehydration and changes in HRV (RMSSD and SD1) were also identified (r = -0.61 to -0.81). CONCLUSION: The current results demonstrated significant relationships between aerobic capacity, body fatness, and hydration status on autonomic control of HR during and after flights. No relationship to muscular strength was observed. Future studies may further elucidate the impact of these factors on pilot training in order to accommodate flight's stressors and enhance performance. PMID- 26564675 TI - Training General Aviation Pilots for Convective Weather Situations. AB - BACKGROUND: Over the past 10-15 yr, considerable research has occurred for the development, testing, and fielding of real-time Datalink weather products for general aviation (GA) pilots to use before and during flight. As is the case with the implementation of most new technologies, work is needed to ensure that the users (in this case, the pilots) understand both the capabilities and limitations of the new technologies as well as how to use the new systems to improve their task performance. The purpose of this study was to replicate and extend a previous study on training pilots how and when to use these new weather technologies. METHOD: This field study used a quasi-experimental design (pre- vs. post-test with a control group). There were 91 GA pilots from the Midwest, Northeastern, and Southeastern United States who participated in a 2-h short course or a control activity. The lecture-based short course covered radar basics, Next Generation Weather Radar (NEXRAD), NEXRAD specifics/limitations, thunderstorm basics, radar products, and decision making. RESULTS: The pilots who participated in the course earned higher knowledge test scores, improved at applying the concepts in paper-based flight scenarios, had higher self-efficacy in post-training assessments as compared to pre-training assessments, and also performed better than did control subjects on post-test knowledge and skills assessments. DISCUSSION: GA pilots lack knowledge about real-time Datalink weather technology. This study indicates that a relatively short training program was effective for fostering Datalink weather-related knowledge and skills in GA pilots. PMID- 26564676 TI - A Randomized Controlled Trial of Core Strengthening Exercises in Helicopter Crewmembers with Low Back Pain. AB - BACKGROUND: The purpose of this study was to determine if five core strengthening exercises would decrease pain severity and related disability in U.S. Air Force helicopter aircrew members with low back pain. METHODS: The study was a randomized control group repeated measures design. The experimental manipulation consisted of a set of five core strengthening exercises performed 4 d/wk for 12 wk. Self-reported pain severity and disability were ascertained at baseline and 12 wk using the Numerical Pain Rating Scale (NPRS) and Modified Oswestry Low Back Pain Disability Index (MODI), respectively. The NPRS was used to ascertain both daily pain (NPRS(daily)) and in-flight pain (NPRS(flight)). Self-reported improvement or deterioration in low back pain was measured using the Global Rating of Change Scale (GRCS). RESULTS: There were 12 subjects enrolled and 5 were randomized to the intervention group. The mean NPRS(flight) score decreased 1.8 points vs. increasing 0.1 points during the trial for the intervention and control groups, respectively. The mean MODI score decreased 4.8 points vs. increasing 1.7 points during the trial for the intervention and control groups, respectively. The mean GRCS score at the end of the trial was 4.0 vs. 0 for the intervention and control groups, respectively. There was no difference between groups in terms of mean NPRS(daily) scores. CONCLUSIONS: Core strengthening exercises were effective in reducing in-flight pain and led to a reduction in pain symptoms and disability over the 12-wk study period as compared to those subjects who maintained their regular exercise regimen. PMID- 26564677 TI - Quality of Life, Health, and Sleep of Air Traffic Controllers with Different Shift Systems. AB - BACKGROUND: Air traffic controllers (ATC) work shifts and their work schedules vary according to the characteristics of each airport. The human body adapts to shiftwork differently. These adjustments affect the health-disease process, predisposing ATC to risk conditions associated with sleep deprivation and lack of night sleep, which can lead to conditions such as cardiovascular diseases, mood disorders, anxiety, and obesity. This study investigated the characteristics of health, sleep, and quality of life of ATC exposed to 8-h alternate work shifts and 6-h rotational work shifts. METHODS: The study was cross-sectional with convenience samples consisting of 84 ATC from two international airports in Brazil. We applied questionnaires to collect data about socioeconomic conditions, quality of life, sleep, and physical activity levels. We also collected health data regarding nutritional status, body composition, and blood pressure. We analyzed the differences between ATC from the two airports considering the variables of sleep, quality of life, and health. RESULTS: Differences were found between the groups in terms of body fat percentage (30.7% and 27.8%), scores of overall quality of life (56.2 and 68), concentration (3.37 and 3.96), energy (3.12 and 3.62), and sleep time on working days (5:20 h and 6:15 h). CONCLUSION: ATC under 8-h alternate shifts showed lower scores for quality of life, higher body fat, and less sleep time on working days, which characterizes inadequate shiftwork for this population. PMID- 26564678 TI - Sleep Duration in Rough Sea Conditions. AB - INTRODUCTION: Environmental motion can affect shipboard sleep of crewmembers. Slamming and similar harsh motion may interfere with sleep, whereas mild motion and sopite syndrome may enhance sleep. If sleep needs vary by sea condition, this factor should be considered when assessing human performance at sea. The goal of this study was to assess sleep duration in different sea conditions. METHODS: Crewmembers (N = 52) from a U.S. Navy vessel participated in the study while performing their normal daily schedule of duties. Sleep was assessed with wrist worn actigraphy. Motion sickness and sopite syndrome were assessed using standardized questionnaires. RESULTS: In rough sea conditions, crewmembers experienced increased severity of motion sickness and sopite syndrome compared to their ratings during calmer sea conditions. Crewmembers slept significantly longer during sea state 5-6 compared to sleep on days with sea state 4 (25% increase) and sea state 3-4 (30% increase). Specifically, daily sleep increased from 6.97 +/- 1.24 h in sea state 3-4, to 7.23 +/- 1.65 h in sea state 4, to 9.04 +/- 2.90 h in sea state 5-6. DISCUSSION: Although the duration of sleep in rough seas increased significantly compared to calmer sea conditions, causal factors are inconclusive. Accumulated sleep debt, motion-induced fatigue, and sopite syndrome all may have contributed, but results suggest that motion sickness and sopite syndrome were the predominant stressors. If sleep needs increase in severe motion environments, this factor should be taken into account when developing daily activity schedules or when modeling manning requirements on modern ships. PMID- 26564679 TI - Conservative Management of Mechanical Neck Pain in a Helicopter Pilot. AB - BACKGROUND: Acute and chronic spinal symptoms such as neck pain may limit flying performance significantly and disqualify the pilot from flight duty. Mechanical neck pain is very common among pilots because of their exposure to vibration, +GZ forces, helmet weight, poor neck posture during air combat maneuvers, previous neck injuries, and poor treatment plans for such injuries. Successful treatment of such injuries requires appropriate therapeutic procedures as well as an aeromedical assessment. The aim of this case study was to demonstrate the benefits of conservative procedures such as spinal manipulation and mobilization therapy (SMMT) and exercise therapy (ET) in treating chronic mechanical neck pain in an Iranian commercial helicopter pilot. CASE REPORT: A 36-yr-old male patient presented to the clinic with moderate, intermittent nonradicular chronic neck pain and limited range of motion over a 2-yr period. The patient was treated with cervical and upper thoracic SMMT followed by home ET for 5 wk. After this period, the patient reported significant recovery and improvement in range of motion in his neck. DISCUSSION: Mechanical neck pain is very common among helicopter pilots. Although Air Force and Navy waiver guides recommend nonsteroidal anti inflammatory medications as well as SMMT and ET, there are currently very few published studies that examine the benefits of manual and exercise therapy for treating mechanical neck pain in commercial and military pilots. Based on the results of this study, it seems that SMMT and ET may be a safe and effective in treatment of uncomplicated mechanical neck pain in helicopter pilots. Alagha B. Conservative management of mechanical neck pain in a helicopter pilot. PMID- 26564680 TI - On-Site 3D Printing of Functional Custom Mallet Splints for Mars Analogue Crewmembers. AB - INTRODUCTION: The first off-Earth fused deposition modeling (FDM) 3D printer is investigating acrylonitrile butadiene styrene (ABS) thermoplastic manufacturing applications for long-duration space missions. This study assessed the feasibility of FDM 3D printing ABS thermoplastic customized mallet splints on site for Mars analogue crewmembers. METHODS: Seven caliper measurements were taken of the right ring finger of 13 healthy Mars Desert Research Station mission crewmembers. These measurements were input into a free 3D modeling software program to create customized digital splint models. These digital files were uploaded to a desktop FDM 3D printer and custom splints were printed on site with ABS thermoplastic. Splint fit was assessed via subject feedback. Joint active range of motion was recorded when the splint was worn briefly. RESULTS: The time it took the software program to digitally render each splint model was less than 2 min and 30 s. The print duration for the splints ranged from 21 to 29 min. All 13 subjects reported that their 3D printed custom mallet splints fit securely and comfortably. All splints permitted full active range of motion of the proximal interphalangeal joint (0-100 degrees ) while maintaining the distal interphalangeal joint in extension. DISCUSSION: It is feasible to 3D print functional ABS thermoplastic custom mallet splints on site for Mars analogue crewmembers. This technology could be used clinically in the future when a custom mallet splint is required in a remote, resource-constrained setting. PMID- 26564681 TI - Humans Are Still the Critical Factor in Aviation Security. AB - INTRODUCTION: In Germany, the German Federal Police assess the performance of aviation security screeners on a regular basis. These so-called "reality tests" are unannounced examinations which aim to investigate whether airport screeners can detect forbidden items in hand luggage or attached to the body. Recent alarming results of such inspections showed clearly that the overall detection rate is in need of improvement. To achieve this, it is important to identify specific factors that influence general screening performance. This especially includes basic cognitive functions like visual screening, alertness, and divided attention, which have come more and more into focus in current fundamental research projects. This brief commentary points out critical factors, contributes background conditions in aviation security screening, and shows possible approaches for enhancement and optimization. Finally, the human aspect is discussed as not only being the weakest factor in security screening, but also one of major importance. PMID- 26564682 TI - You're the Flight Surgeon. PMID- 26564683 TI - You're the Flight Surgeon. PMID- 26564684 TI - Blind Flying: The Origins of Instrument Flying. PMID- 26564685 TI - This Month in Aerospace Medicine History. PMID- 26564687 TI - [Management of impacted cuspid--July 2015]. AB - The French Society of Stomatology, Oral and Maxillofacial Surgery (SFSCMFCO) together with the Medical Society of Dento-Maxillofacial Orthopedics has drawn up in 2015 a new practice guideline concerning the management of one or several impacted cuspids. As the previous ones, this guideline is based on a rigorous French Heath Regulation Authorities type methodology. It is thus intended to become a major reference in its field. We report hereafter the short version of the text in the same way it has been presented during the 2015 French National Congress of the SFSCMFCO in Lyon - France. Each of these recommendations is marked A, B or C according to a decreasing evidence based rating scale. Lacking any evidence-based data, the recommendation is considered as an expert opinion (AE). The full text of this guideline is available on the website of the SFSCMFCO at the following address: http://www.sfscmfco.fr/; "Recommandations de bonnes pratiques" section. A patient information sheet is also proposed by the working group. Happy reading. PMID- 26564686 TI - Evidence for surprise minimization over value maximization in choice behavior. AB - Classical economic models are predicated on the idea that the ultimate aim of choice is to maximize utility or reward. In contrast, an alternative perspective highlights the fact that adaptive behavior requires agents' to model their environment and minimize surprise about the states they frequent. We propose that choice behavior can be more accurately accounted for by surprise minimization compared to reward or utility maximization alone. Minimizing surprise makes a prediction at variance with expected utility models; namely, that in addition to attaining valuable states, agents attempt to maximize the entropy over outcomes and thus 'keep their options open'. We tested this prediction using a simple binary choice paradigm and show that human decision-making is better explained by surprise minimization compared to utility maximization. Furthermore, we replicated this entropy-seeking behavior in a control task with no explicit utilities. These findings highlight a limitation of purely economic motivations in explaining choice behavior and instead emphasize the importance of belief based motivations. PMID- 26564688 TI - Protein breakdown in cancer cachexia. AB - Skeletal muscle is a highly adaptive tissue, capable of altering muscle fiber size, functional capacity and metabolism in response to physiological stimuli. However, pathological conditions such as cancer growth compromise the mechanisms that regulate muscle homeostasis, resulting in loss of muscle mass, functional impairment and compromised metabolism. This tumor-induced condition is characterized by enhanced muscle protein breakdown and amino acids release that sustain liver gluconeogenesis and tissue protein synthesis. Proteolysis is controlled by the two most important cellular degradation systems, the ubiquitin proteasome and autophagy lysosome. These systems are carefully regulated by different signalling pathways that determine protein and organelle turnover. In this review we will describe the involvement of the ubiquitin proteasome and autophagy lysosome systems in cancer cachexia and the principal signalling pathways that regulate tumor-induced protein breakdown in muscle. PMID- 26564689 TI - Early development of the vertebral column. AB - The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis. PMID- 26564690 TI - [Study on drop-out from antiretroviral therapy among adult HIV-infected individuals in Dehong prefecture, Yunnan province]. AB - OBJECTIVE: To examine the proportion and reasons of drop-out from antiretroviral therapy (ART) among 8 367 adult HIV-infected individuals in Dehong prefecture, Yunnan province. METHODS: All adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART. RESULTS: The proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4% (1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as: living area, gender, age, marital status, HIV transmission route, baseline CD4+ T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model, drop-out from ART was significantly correlated with residential area, marital status, HIV transmission route, baseline CD4+ T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city, Lianghe county or Yingjiang County, being married or living with partner, HIV infection through sexual contact, with baseline CD4+ T cell counts <= 200 cells/mm3, and ART included in the initial treatment regimen etc., were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART, 704 (58.6%) were lost to follow-up, 303 (25.2%) did not adhere to treatment, 74 (6.2%) moved out the region, 64 (5.3%) were Burmese that had returned to Burma, 29 (2.4%) stopped the treatment according to doctors' advice, 18 (1.5%) were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied, according to the situation of patients. CONCLUSION: The proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence. PMID- 26564691 TI - [Compliance of antiviral therapy and influencing factors in people living with HIV/AIDS in Nanjing]. AB - OBJECTIVE: To understand the compliance of highly active anti-retroviral therapy (HAART) and influencing factors in people living with HIV/AIDS (PLWHA) in Nanjing. METHODS: PLWHA receiving HAART in No. 2 Hospital of Nanjing during May June 2014 were recruited in this study. Self-administrated questionnaire was used to collect the data about HAART compliance and socio-demographic characteristics of PLWHA surveyed. Descriptive and multivariate statistical analysis were conducted to examine the effects of the factors on self-reported HAART adherence. RESULTS: A total of 276 PLWHA were surveyed, According to the evaluation criterion of Center for Adherence Support Evaluation (CASE), 252 cases showed good compliance (91.3%). logistic regression analysis revealed that smoking, progress of the disease and side effects, reminding of taking drug and age were correlated with self-reported HAART adherence. CONCLUSION: It is suggested to strengthen the education about antiviral therapy compliance in PLWHA with mild infection and those who are smokers and young, suffer from side effects, have no reminding methods for taking drug. PMID- 26564692 TI - [Social support for 330 HIV/AIDS patients under antiretroviral treatment and related factors in Wuhan]. AB - OBJECTIVE: To investigate the current status of social support for HIV/AIDS patients under antiretroviral treatment (ART) and related factors in Wuhan. METHODS: Social Support Rating Scale (SSRS) was used to analyze the current status of social support for HIV/AIDS patients under ART in Wuhan. Student's t test, analysis of variance (ANOVA) and multiple linear regression model were used to identify the related factors. RESULTS: The scores of subjective support, objective support, utilization of social support, and overall social support for 330 HIV/AIDS patients were significant lower than the national norm (P < 0.05). Multiple linear regression analysis showed that the subjective support (beta' = 0.260), objective support (beta' = -0.196) and overall social support (beta' = 0.141) for the patients who were unmarried, divorced or widowed were worse than those for the patients who were married (P < 0.05). The patients with higher educational level had more objective support (beta' = 0.250) and utilization of social support (beta' = 0.232) than those with lower educational level (P < 0.05). The subjective support for patients without HIV related symptoms in the past two weeks was better than those with HIV related symptoms (beta' = 0.232, P < 0.05). CONCLUSION: The current status of social support for HIV/AIDS patients under ART in Wuhan was worse than that for healthy people. More attention should be paid to HIV/AIDS patients with worse social support. PMID- 26564693 TI - [Association between anemia and 3-year all-cause mortality among oldest old people in longevity areas in China]. AB - OBJECTIVE: To explore the association between anemia and 3-year all-cause mortality among the oldest old people in longevity areas in China. METHODS: In August 2012, questionnaire survey, health examination and blood test were conducted among 929 old people aged >= 80 years in 7 longevity areas in China, who were included in Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2009. Cox regression model was used to evaluate the association between anemia or different hemoglobin levels and mortality. RESULTS: Among the 929 subjects, the prevalence of anemia was 49.6%, the main form of anemia was normocytic anemia. During the three year follow-up period, a total of 447 subjects died, the overall mortality was 49.8% (56.0% in subjects with anemia and 43.3% in subjects without anemia). Compared with the subjects without anemia, the mortality risk increased by 25% in the subjects with anemia after adjusting confounding factors (HR = 1.25, 95% CI: 1.03-1.52). Macrocytic anemia, simplex microcytic anemia and microcytic hypochromic anemia were all associated with the increased mortality in the oldest old people. Compared with the subjects with low hemoglobin concentration, the subjects with high hemoglobin concentration had a lower mortality risk, and the association was more obvious in women. CONCLUSION: Anemia and low hemoglobin concentration were associated with higher mortality risk in the oldest old people in China, indicating the importance of anemia prevention and treatment among this population. PMID- 26564694 TI - [Risk factors for cardiovascular disease and their clustering among middle aged and old people in Jilin province]. AB - OBJECTIVE: To understand the risk factors for cardiovascular disease (CVD) and their clustering among middle aged and old people in Jilin province and provide evidence for the development of effective intervention measures. METHODS: A total of 13 914 people aged 35-79 years were selected from 32 counties (district) in 9 prefectures (municipality) of Jilin province through multi-stage stratified cluster sampling to conduct a face to face questionnaire survey and health examination. Complex weighted computation was conducted to analyze the survey results. RESULTS: The prevalence of hypertension, diabetes, dyslipidemia, smoking and overweight were 41.3%, 11.5%, 42.8%, 31.5% and 53.5%, respectively. Only 16.2% of the subjects surveyed were free of the 5 risk factors. >= 1 risk factor and >= 3 risk factors were found to clustering in 83.8% and 29.9% of the middle aged and old people. Compared with females, the odds ratios of >= 1, >= 2 and >= 3 risk factors clustering in males were 3.18, 4.28 and 5.58 times higher, respectively. Compared with urban residents, the odds ratios of >= 1, >= 2 risk factors clustering in rural residents were 1.22 and 1.20 times higher. In addition, the odds ratios of >= 1, >= 2 and >= 3 risk factors clustering increased with age (all P < 0.001). CONCLUSION: High prevalence of major cardiovascular disease risk factors and their clustering were found in middle aged and old people in Jilin province. More attention and intervention should be given to the old males in rural areas. PMID- 26564695 TI - [Mediating effect of blood lipids on correlation between body fat and blood pressure among overweight adults]. AB - OBJECTIVE: To understand the mediating effect of blood lipids on the correlation between body fat and blood pressure among overweight adults. METHODS: Overweight and obese subjects aged 20-55 years who had lived in Beijing for at least 1 year were recruited in this study, Body mass index (BMI) was used as a screening indicators. The percentage of body fat (PBF) was measured for the subjects by using dual energy X-ray absorptiometry (DXA). Mediating effect analysis was conducted to analyze the mediating effect of blood lipids on correlation between PBF and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). RESULTS: After adjusting for age, PBF was positively correlated with SBP and DBP in both males (beta = 0.208 3, beta = 0.205 2, P < 0.001) and females (beta = 0.188 4, beta = 0.209 6, P < 0.001). In male subgroup, PBF was negatively correlated with HDL-C level, but positively correlated with LDL-C level (beta = 0.142 2, P < 0.01 and beta = 0.180 5, P < 0.001), while in female subgroup, PBF was positively correlated with both TC level and LDL-C level (beta = 0.172 1, P < 0.001 and beta = 0.233 5, P < 0.001). With PBF controlled, TC and TG levels were positively correlated with DBP in both males and females (beta = 0.095 6, 0.090 5 for males, beta = 0.117 6, 0.083 1 for females, P < 0.05), and TG level was positively correlated with SBP in females (beta = 0.127 2, P < 0.001). Further analysis indicated there was a significant mediating effect of LDL-C on correlation between PBF and DBP in females, with the mediating effect value of 0.019 4 (P < 0.05). The ratio of mediating effect was 9.26%. CONCLUSION: PBF was positively correlated with blood pressure, but blood lipids had no mediating effect on the correlation between PBF and blood pressure in males, while LDL-C level had mediating effect on PBF and blood pressure in females. PMID- 26564696 TI - [Epidemiological investigation of macrosomia-related knowledge awareness among pregnant women in Zhejiang province]. AB - OBJECTIVE: To understand the awareness rate of macrosomia related knowledge and influencing factors among pregnant women in Zhejiang province and provide evidence for the improvement of pre-gestational and prenatal care. METHODS: A face to face questionnaire survey was conducted among 1 512 pregnant women selected through multistage cluster random sampling from 20 counties (district) in Zhejiang. Macrosomia-related awareness and related factors were analyzed. RESULTS: A total of 1 494 valid questionnaires were analyzed, the awareness rate was 40.7% for macrosomia diagnostic criteria (95% CI: 38.2%-43.2%), 55.0% for the cause of macrosomia (95% CI: 52.4%-57.6%) and 62.4% for prevention related knowledge (95% CI: 59.9%-64.9%) and the awareness rate of both the cause and the prevention related knowledge was 49.0% (95% CI: 46.4%-51.6%). Multivariate logistic regression analysis showed that the third trimester of pregnancy (OR = 1.906, 95% CI: 1.128-3.221), urban residence (OR = 1.335, 95% CI: 1.014-1.756), educational level of junior college (OR = 2.474, 95% CI: 1.635-3.744) and educational level of regular college or above (OR = 2.072, 95% CI: 1.338-3.209), receiving health education about health pregnancy (OR = 1.936, 95% CI: 1.509 2.484) and self-learning about the knowledge of health pregnancy (OR = 2.065, 95%CI: 1.338-3.189) were the influencing factors to the awareness rate of macrosomia diagnostic criteria and prevention related knowledge of macrosomia among pregnant women. The awareness rate of the cause and prevention related knowledge of macrosomia was higher in older age group (OR = 2.103, 95% CI: 1.330 3.323). CONCLUSION: Among the pregnant women in Zhejiang, the awareness rate of macrosomia diagnostic criteria was less than 50%. Therefore, it was necessary to strengthen the health education during pre-gestational and gestational periods among reproductive women, especially the education about pregnancy health in rural area. PMID- 26564697 TI - [Comparison of consistency in measurement of body fat percentage by dual-energy X ray absorptiometry and multi-frequency bioelectrical impedance analysis in overweight and obese adults in China]. AB - OBJECTIVE: To compare the consistency in the measurement of percentage of body fat (PBF) by multi-frequency bioelectrical impedance analysis (MF-BIA) and dual energy X-ray absorptiometry (DXA) in overweight and obese adults in China, and provide evidence for the accurate MF-BIA application in China. METHODS: A total of 1 323 overweight/obese adults aged 22-55 years were recruited in this study. All the subjects received PBF measurement by both MF-BIA and DXA. The consistency in PBF measurement by MF-BIA and DXA was evaluated by using interclass correlation coefficients (ICC), then the correction prediction models was established. RESULTS: The differences in PBF measurement in male subjects and female subjects between MF-BIA and DXA were statistical significant (all P < 0.01), the mean difference values were -6.5% for overweight males and -4.3% for obese males, -2.5% for overweight females and 0.5% for obese females, respectively. The difference in ICC of PBF between MF-BIA and DXA measurement were statistically significant in all subgroups (P < 0.01). The ICC was 0.746 for overweight males, 0.807 for obese males, 0.628 for overweight females and 0.674 for obese females, respectively. The correction prediction models included: PBF (DXA) = 13.425 + 0.719 * PBF (MF-BIA) for overweight males; PBF (DXA) = 12.572 + 0.741 * PBF (MF-BIA) for obese males; PBF (DXA) = 9.785 + 0.802 * PBF (MF-BIA) for overweight females; PBF (DXA) = 20.348 + 0.532 * PBF (MF-BIA) for obese females. CONCLUSION: The consistency in PBF measurement in overweight/obese adults by MF-BIA and DXA was poor in China. Correction should be conducted when MF-BIA is used in the measurement of PBF. PMID- 26564698 TI - [Epidemiological characteristics of influenza outbreaks in China, 2005-2013]. AB - OBJECTIVE: To understand the epidemiological characteristics of influenza outbreaks in China from 2005 to 2013. METHODS: The data of influenza-like illness outbreaks involving 10 or more cases were collected through Public Health Emergency Management Information System and National Influenza Surveillance Information System in China, and the influenza outbreaks were identified according to the laboratory detection results. Descriptive epidemiological analysis was conducted to understand the type/subtype of influenza virus and outbreak time, area, place and extent. RESULTS: From 2005 to 2013, a total of 3 252 influenza-like illness outbreaks were reported in the mainland of China, in which 2 915 influenza outbreaks were laboratory confirmed, and influenza A (H1N1) pdm09 virus and influenza B virus were predominant. More influenza outbreaks were reported in the influenza A (H1N1) pandemic during 2009-2010. Influenza outbreaks mainly occurred during winter-spring, and less influenza outbreaks occurred in winter and summer vacations of schools. More influenza outbreaks were reported in southern provinces, accounting for 79% of the total. Influenza outbreaks mainly occurred in primary and middle schools, where 2 763 outbreaks were reported, accounting for 85% of the total. Average 30-99 people were involved in an outbreak. CONCLUSION: A large number of influenza outbreaks occur during influenza season every year in China, the predominant virus type or subtype varies with season. Primary and middle schools are mainly affected by influenza outbreaks. PMID- 26564699 TI - [Burden of colorectal cancer in China]. AB - OBJECTIVE: To understand the incidence and mortality of colorectal cancer in China. METHODS: The data from GLOBOCAN 2012, Chinese Cancer Registry Annual Report 2012, Cancer Incidence in Five Continents (CI5), the Three National Death Cause Surveys in China and WHO Mortality Database were used to learn about the incidence and mortality of colorectal cancer and related trends in China. RESULTS: It was estimated by GLOBOCAN 2012 that in 2012 the age-standardized incidence of colorectal cancer in China was 16.9 per 100 000 in males and 11.6 per 100 000 in females, and the age-standardized mortality was 9.0 per 100 000 in males and 6.1 per 100 000 in females. GLOBOCAN 2012 estimated that colorectal cancer incidence and mortality would increase with the level of human development index. China's human development level was high, suggesting that the burden of colorectal cancer would be more serious in China with the development of social economy. The data from CI5 Volume IV and GLOBOCAN 2012 indicated that the incidence of colorectal cancer began to increase obviously at age of 50 years in China. Chinese Cancer Registry Annual Report 2012 showed that the incidence and mortality of colorectal cancer in urban population were two times higher than those in rural population in 2009, the proportions of colon cancer among colorectal and anus cancers, which was 49.0% in males and 54.2% in females, 53.4% in urban population and 41.7% in rural population. CI5 Volumes IV-X showed that colon cancer and rectum and anus cancer incidence in Shanghai for both males and females were increasing during the period 1973-2007. The percentage change in colon cancer and rectum and anus cancer incidence between 1973-1977 and 2003-2007 increased by 138.8% and 31.1% in males, 146.7% and 49.1% in females, respectively. The data from the Three National Death Cause Surveys showed that the crude mortality of colorectal cancer increased by 77.9% form mid 1970's (1973 1975) to mid 2000's (2004-2005). WHO Mortality Database showed that average annual percentage change (AAPC) of age-standardized colorectal cancer mortality increased by 0.7% (P < 0.05) from 1987 to 2000. CONCLUSION: More attention should be paid to the prevention and control of colorectal cancer in urban area and in male population in China. Similar to the western countries, the burden of colorectal cancer in China would continue to become serious if no population based prevention and control programs are conducted. PMID- 26564700 TI - [Trend of dietary nutrient intake among adult females in 9 provinces in China, 2000-2011]. AB - OBJECTIVE: To investigate trend of dietary nutrient intake among adult females in China. METHODS: The changes of dietary energy and major nutrient intake among females aged 25 to 55 years in 9 provinces were analyzed by using the data from Chinese Health and Nutrition Survey, 2000-2011 (CHNS) and indicators of Chinese Dietary Reference Intakes (DRIs) 2013. RESULTS: During the past decade, the proportion of females with the intake of energy and protein meeting the requirement of recommendation decreased, while the proportion of females with low carbohydrate (< 50% energy) and high fat (> 30% energy) intakes increased. Meanwhile, the vitamin and mineral intakes among the females were also unsatisfactory, only small proportion of the females met the requirement for micronutrient intake, and this proportion continued to decline. In 2011, the proportion of the females who met the requirements for energy and protein intakes were 43.0% and 54.4%, respectively; the proportion of the females with low carbohydrate and high fat intakes were 40.2% and 63.8%, respectively; the proportion of females who met the requirements for vitamin A, thiamine, riboflavin, niacin, vitamin C and vitamin E intakes were 25.2%, 10.7%, 6.9%, 54.9%, 24.3% and 88.5% respectively and the proportion of females who met the requirements for calcium, magnesium, iron, zinc and selenium intakes were 3.3%, 23.6%, 50.9%, 75.7% and 13.3% respectively. CONCLUSION: Further nutritional education and intervention is needed to improve nutrition status among Chinese females. PMID- 26564701 TI - [Impact of air temperature on years of life lost among residents in Guangzhou and Zhuhai: a time-series study]. AB - OBJECTIVE: To evaluate the impacts of air temperature on years of life lost (YLL) among the residents in Guangzhou and Zhuhai, Guangdong province. METHODS: Daily mortality and meteorology data in Guangzhou and Zhuhai were collected, and distributed lag non-linear model (DLNM) was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature (0-1 days) and extreme low temperature (0-13 days) situation in Guangzhou and Zhuhai were analyzed respectively. RESULTS: The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day, while the cold effect reached the peak at 5(th) days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged >= 65 years than in people aged < 65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai. CONCLUSION: The effects of high and low temperatures on YLL were obvious, and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations. PMID- 26564702 TI - [Relationship between hepatitis B virus genotype, BCP/Pre-C region mutations and risk of hepatocellular carcinoma in Guangxi Zhuang Autonomous Region]. AB - OBJECTIVE: To investigate the relationship between hepatitis B virus (HBV) genotype, the mutation in basic core promoter (BCP) region/pre-core (Pre-C) region and the incidence of hepatocellular carcinoma (HCC) in Fusui county of Guangxi Zhuang Autonomous Region (Guangxi), a area with high incidence of HCC. METHODS: In this case-control study, 53 HCC patients and 70 asymptomatic HBV carriers were enrolled. Blood samples were collected from them for serum separation and HBV DNA extraction. The DNA sequences of the S region and BCP/Pre C region of HBV was determined by direct sequencing following nested-PCR amplification. The relationship between the genotype, gene mutation of HBV and the incidence of HCC was analyzed. RESULTS: The mutation rates of the A1762T/G1764A in the BCP region and the T1858C in the Pre-C region of HBV were significantly higher in HCC group than in control group (94.3% vs. 75.7%, P = 0.006; 50.9% vs. 31.4%, P = 0.029). The mutation rate of A1775G was significantly higher in control group (28.6%) than in HCC group (13.2%) (P = 0.041). Multiple logistic regression analysis indicated that A1762T/G1764A and T1858C mutations are the risk factors for the development of HCC (OR = 5.459, 95% CI: 1.397 21.332, P = 0.015; OR = 3.881, 95% CI: 1.462-10.305, P = 0.006). A1775G is the protective factor in the development of HCC (OR = 0.192, 95% CI: 0.059-0.622, P = 0.006). CONCLUSION: The present investigation showed that BCP A1762T/G1764A, A1775G and Pre-C T1858C mutations are correlated with the incidence of HCC in Fusui county of Guangxi. PMID- 26564703 TI - [Infection status of enterovirus 71 and coxsackievirus A16 among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice]. AB - OBJECTIVE: To understand the infection status of enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (HFMD). METHODS: Serological survey was conducted in the local children receiving health examination for child care setting entrance. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EV71 and anti-Cox A16 IgG and IgM. RESULTS: A total of 813 children were surveyed (mean age: 3.5 +/- 1.0 year old). The seropositive rate was 61.9% and 4.4% for anti-Cox A16 IgG and IgM. The seropositive rate was 9.3% and 1.1% for anti-EV71 IgG and IgM. No significant difference was observed in sex specific seropositive rate (P > 0.05). However, significant differences were found in seropositive rate among different age groups (P < 0.05). Among the children who were anti-Cox A16 positive, 7.8% had ever had rashes on their hands and feet, mouth or buttocks (HFMD-like rashes). Among the children who were anti-EV71 positive, 10.7% had ever had HFMD-like rashes. For the children who were anti-Cox A16 or anti-EV71 positive, only 7.1% were brought to see doctors by their parents. However, among the seropositive children with rashes, 80.5% were brought to see doctors. CONCLUSION: In the healthy children at the age to go to child care setting in Beijing, most had ever infected with Cox A16. The anti-EV71 positive rate was much lower than the anti-Cox A16 positive rate. It was necessary to strengthen the prevention and control of EV71 infection in child cares settings. PMID- 26564704 TI - [Genetic characteristics of VP1 region of coxsackievirus A10 strains isolated from hand foot and mouth disease patients in Ningxia Hui Autonomous Region, 2013]. AB - OBJECTIVE: To study the genetic characteristics of VP1 region of coxsackievirus A10 (Cox A10) strains isolated from hand foot and mouth disease (HFMD) cases in Ningxia Hui Autonomous Region (Ningxia) in 2013. METHODS: A total of 280 specimens, which were identified as non-enterovirus 71 and non-Cox A16 by real time PCR, were collected and cultured by using RD cell, and the VP1 genes of isolated strains were amplified by using reverse transcriptase PCR (RT-PCR) with degenerated primers and sequenced. The sequencing results were aligned with the sequences in GenBank with BLAST algorithm to identify the virus genotypes. Homologous comparison and phylogenetic analysis were conducted for all the Cox A10 strains identified. RESULTS: Among 36 virus strains isolated from 280 clinical specimens, 6 were identified as Cox A10. The homologies of nucleotide and amino acid of the Cox A10 strains isolated in Ningxia were 97.0%-99.8% and 99.0%-99.7% respectively, and the Cox A10 strains isolated in Ningxia shared 76.3%-77.2%, 81.6%-83.1%, 94.4%-98.9% and 80.0%-82.3% nucleotide homologies respectively and shared 92.3%-93.0%, 94.0%-95.3%, 98.0%-99.7% and 90.6%-94.0% amino acid homologies respectively with the representative strains of A, B, C and D genotypes. Phylogenetic tree analysis revealed that Cox A10 strains isolated in Ningxia belonged to genotype C. CONCLUSION: Cox A10 is one of the most common pathogen causing HFMD in Ningxia in 2013. All the Cox A10 stains isolated from HFMD patients in Ningxia belonged to genotype C. PMID- 26564705 TI - [Influence of HIV infection on hepatitis C progress in patients co-infected with HIV/HCV]. AB - OBJECTIVE: To understand the influence of HIV infection on hepatitis C progress in patients co-infected with HIV and hepatitis C virus (HCV) and related immune mechanism. METHODS: Twenty eight patients co-infected with HIV/HCV and 12 patients with simplex HCV infection were enrolled. The liver function and hepatic fibrosis progress were evaluated by detecting peripheral blood and with Fibro Scan. The viral load of HCV was detected by using real time quantitative PCR. And the percentage of Treg/CD4+ T lymphocyte cell was tested by using flow cytometry. RESULTS: The levels of ALT and ALP in HIV/HCV co-infection group were (76.16 +/- 81.248) U/L, (24.507 1 +/- 8.194) g/L respectively, higher than those of simplex HCV infection group [(27.475 0 +/- 13.985) U/L, (16.966 7 +/- 7.189) g/L], the differences were statistical significant. P value was 0.012 and 0.009 respectively. The liver fibrosis index in HIV/HCV co-infection group was 5.950 0 5.825 0 Kpa, higher than that in simplex HIV infection group (5.150 0-1.050 0 Kpa), and the difference was nearly statistical significant (P = 0.077). The HCV viral load in HIV/HCV co-infection group was (6.476 8-5.343 4) lg copy/ml, higher than that in simplex HCV infection group [(1.699 0-2.681 5) lg copy/ml], and the rate of HCV clearance in HIV/HCV co-infection group was 32.14%, lower than that in simplex HCV infection group (75.00%). P value was 0.012 and 0.032 respectively. The percentage of Treg/CD4+ T lymphocyte cell in HIV/HCV co infection group was (7.460 0%-2.287 5%), higher than that in simplex HCV infection group (5.965 0%-2.105 0%), and the difference was significant (P = 0.032). The percentage of Treg/CD4+ T lymphocyte cell was significantly related with HCV viral load (rho = 0.350, P = 0.027), and HCV viral load was significantly related with the liver fibrosis index (rho = 0.487, P = 0.001). CONCLUSION: HIV infection could accelerate the progress of hepatitis C, and Treg cells were involved in this progress. PMID- 26564706 TI - [Influence of sedentary behavior on weight retention among postpartum women within one year after childbirth]. AB - OBJECTIVE: To identify the risk factors that affect the postpartum weight retention among women and provide evidence for the prevention of obesity and metabolic disorders due to childbirth. METHODS: The baseline data were collected from 1 220 postpartum women who had given childbirth 42 days ago in Hefei Maternal and Child Health Care Center, Anhui province. Their pre-pregnancy weight, weight gain during pregnancy and childbirth information were obtained from local maternal information management system, and the follow up for the women were conducted at 3, 6, 9, and 12 months after childbirth. The sedentary behaviors of the women were observed. The relationship between postpartum weight retention and sedentary behavior of the women were analyzed by mixed-effects model analysis and repeated measures analysis of variance. RESULTS: The pre pregnancy average body weight (kg) of the women was (53.22 +/- 6.88), and their postpartum average body weight retention was (7.85 +/- 5.11), (7.51 +/- 5.40), (5.79 +/- 5.18), (4.42 +/- 4.91) and (3.26 +/- 4.65) at 42 days, 3, 6, 9, 12 months later after childbirth, respectively. The differences in body weight retention at different times after childbirth indicated by repeated measures analysis of variance were statistical significant (P < 0.001). Mixed-effects model analysis showed the postpartum sedentary behavior and postpartum body weight retention was statistically associated after adjusting for pre-pregnancy BMI, feeding pattern, delivery mode and other confounding factors (P < 0.001), Mixed-effects model analysis results tended to be stable after step by step adjustment for confounding factors. CONCLUSION: The results of this study suggested that postpartum sedentary behavior is one of the important factors influencing postpartum weight retention. PMID- 26564707 TI - [Risk factors of 125 cases of neonatal congenital hypothyroidism during perinatal period]. AB - OBJECTIVE: To understand the relationship between perinatal factors and congenital hypothyroidism (CH) and provide scientific evidence for the prevention of CH. METHODS: A case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH (control group) in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period. RESULTS: Univariate logistic regression analysis indicated that compared with control group, gestational hypertension, gestational diabetes mellitus, gestational thyroid disease and older age of mother were the risk factors to CH, the difference was statistically significant (P < 0.05) and the risk of CH was higher in female babies, preterm babies, post term babies low birth weight babies, macrosomia, twins, babies with birth defects and infection in cases group than those in control group, the difference was statistically significant (P < 0.05). Multivariate logistic analysis showed that older age of mother (OR = 2.518, 95% CI: 1.186-5.347), gestational diabetes mellitus (OR = 1.904, 95% CI: 1.190-3.045), gestational hypothyroidism or hyperthyroidism (OR = 12.883 and 30.797, 95% CI: 2.055-80.751 and 3.309-286.594), preterm birth (OR = 4.238, 95% CI: 1.269-14.155), and post-term birth (OR = 12.799, 95% CI: 1.257-130.327), low birth weight (OR = 3.505, 95% CI: 1.059 11.601), macrosomia (OR = 3.733, 95% CI: 1.415-9.851), twin or multiparous delivery (OR = 5.493, 95% CI: 1.701-17.735), birth defects (OR = 3.665, 95% CI: 1.604-8.371) and fetal distress (OR = 3.130, 95% CI: 1.317-7.440) were the high risk factors to CH (P < 0.05). CONCLUSION: CH was correlated with mother's age, gestational diabetes, gestational thyroid disease as well as neonate's birth weight and gestational age, foetus number, fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH. PMID- 26564708 TI - [Meta-analysis of HIV infection incidence and risk factors among men who have sex with men in China]. AB - OBJECTIVE: To understand the incidence of HIV infection among men who have sex with men (MSM) in China. METHODS: Meta-analysis was performed to systematically and quantitatively review all the original research papers and reports published during 2010-2015 on the incidence of HIV infection among MSM in China. Pooled incidence, pooled hazard ratios, publication bias, heterogeneity and sensitivity analysis for those studies were calculated or analyzed by using Stata 12.0 software. RESULTS: A total of 24 studies were analyzed. Pooled incidence of HIV infection among MSM in China was 5.0/100 person year; Based on HIV case report, severe epidemic areas had higher HIV incidence than other areas (4.9/100 person year vs. 3.4/100 person year). Low education level (HR = 1.61, 95% CI: 1.21 2.15), syphilis prevalence (HR = 3.22, 95% CI: 2.21-4.70), unprotected anal sex (HR = 2.92, 95% CI: 1.51-5.63), minority ethnic group (HR = 4.01, 95% CI: 1.96 8.21), commercial sex (HR = 4.11, 95% CI: 1.47-11.46) and multiple sexual partners (HR = 2.31, 95% CI: 1.60-3.34) were the risk factors for HIV incidence. CONCLUSION: Pooled incidence of HIV infection among MSM was 5.0% in China. Low education level, syphilis prevalence, unprotected anal sex, minority ethnic group, commercial sex and multiple sexual partners were the risk factors for HIV infection. PMID- 26564709 TI - [Application of Marginal Structural Models to control timedependent confounding bias]. PMID- 26564710 TI - [Molecular pathological epidemiology]. PMID- 26564711 TI - [A review on the epidemiology of Middle East Respiratory Syndrome]. PMID- 26564712 TI - [A review on progress of tobacco control in hospitality venues]. PMID- 26564713 TI - Collagenase 1A2 (COL1A2) gene A/C polymorphism in relation to severity of dental fluorosis. AB - OBJECTIVES: The aim of this study was to evaluate the putative association between the presence of the COL1A2 gene A/C polymorphism and the severity of dental fluorosis in a sample exposed to high concentrations of fluoride. METHODS: A cross-sectional study was carried out that included 80 children residing in a community with high concentrations of fluoride in the drinking water. To determine whether the presence of this polymorphism and dental fluorosis are associated, the presence of the dental fluorosis was considered to be a response variable, while fluoride concentration in water and urine was designated as independent variables. In addition, the children's parents completed questionnaires with general information about drinking and cooking with tap water, consumption of milk and soft drinks, and other putative risk factors. RESULTS: Individuals with the polymorphism had nonsignificant odds (OR = 2.24; 95% CI = 0.55-9.02) of having dental fluorosis at higher exposures to fluoride. This finding was similar in individuals without the polymorphism (OR = 1.65; 95% CI = 0.44-6.17). CONCLUSIONS: The presence of polymorphism in the COL1A2 gene was not associated with the severity of dental fluorosis. PMID- 26564714 TI - Nomograms for mitral inflow Doppler and tissue Doppler velocities in Caucasian children. AB - BACKGROUND: Pediatric echocardiographic nomograms for systolic/diastolic functional indices are limited by small sample size and inconsistent methodologies. Our aim was to establish pediatric nomograms for mitral valve (MV) pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) velocities. METHODS: We performed PWD/TDI measurements of MV velocities and generated models testing for linear/logarithmic/exponential/square root relationships. Heteroscedasticity was accounted for by White test or Breusch-Pagan test. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. RESULTS: In all, 904 Caucasian Italian healthy children (age 0 days-17 years; 45.5% females; BSA 0.12-2.12m(2)) were prospectively studied. No individual variable provided equations with an acceptable coefficient of determination (R(2)) and even the inclusion of multiple variables in the model resulted in only a partial amelioration of the R(2). Higher R(2) were obtained for PWD-E deceleration time (0.53), septal (Se') and lateral (Le') MV-TDI e' velocity (Se': 0.54; Le': 0.55). Variability was higher at lower age and BSA. In older children patterns were more reproducible; however, the exclusion of neonates did not substantially improve the final models. The low R(2) hampered building of z-scores and calculation of estimated percentiles. Thus normative data have been presented as observed percentile according to age for all measurements. CONCLUSIONS: We report normal ranges for PWD and TDI mitral velocities derived from a large population of Caucasian children. Variability of diastolic patterns especially at lower ages needs to be taken into account. PMID- 26564715 TI - Glial cell line-derived neurotrophic factor protects against high-fat diet induced hepatic steatosis by suppressing hepatic PPAR-gamma expression. AB - Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-gamma (PPAR gamma) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-gamma gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID- 26564716 TI - Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice. AB - The aim of this study was to determine the effect of iron overload in the development of nonalcoholic steatohepatitis (NASH) in a genetically obese mouse model (Lepr(db/db)). Leptin receptor-deficient mice were fed a normal or an iron supplemented chow for 8 wk and switched to normal chow for 8 wk. All dietary iron (DI)-fed mice developed hepatic iron overload predominantly in the reticuloendothelial system. Hepatocellular ballooning injury was observed in the livers of 85% of DI mice, relative to 20% of chow-fed Lepr(db/db). Hepatic malonyldialdehyde levels and mRNA levels of antioxidant genes (Nrf2, Gpx1, and Hmox1) were significantly increased in the DI mice. Hepatic mRNA levels of mitochondrial biogenesis regulators Pgc1alpha, Tfam, Cox4, and Nrf1 were diminished in the DI mice. In addition, gene expression levels of cytokines (Il6, Tnfalpha) and several innate and adaptive immune cell markers such as Tlr4, Inos, CD11c, CD4, CD8, and Ifngamma were significantly increased in livers of the DI group. Strikingly, Nlrp3, a component of the inflammasome and Il18, a cytokine elicited by inflammasome activation, were significantly upregulated in the livers of DI mice. In addition, RAW 264.7 macrophages loaded with exogenous iron showed significantly higher levels of inflammatory markers (Inos, Tnfalpha, Mcp1, Tlr4). Thus dietary iron excess leads to hepatic oxidative stress, inflammasome activation, induction of inflammatory and immune mediators, hepatocellular ballooning injury, and therefore NASH in this model. Taken together, these studies indicate a multifactorial role for iron overload in the pathogenesis of NASH in the setting of obesity and metabolic syndrome. PMID- 26564717 TI - Dysregulation of bile acid homeostasis in parenteral nutrition mouse model. AB - Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12alpha-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-alpha (LXRalpha) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-alpha (RORalpha) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRalpha function. Western blot showed significantly reduced nuclear migration of RORalpha protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORalpha signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD. PMID- 26564718 TI - Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver. AB - Podoplanin/gp38(+) stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38(+) cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38(+) cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38(+) cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38(+) cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45(-)CD31(-)Asgpr1(-) liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38(hi)CD133(-), gp38(low)CD133(-), and gp38( )CD133(-)). Moreover, among the CD133(+) cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38(-)CD133(+) and CD133(+)gp38(+)). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38(+)CD133(+) cells exhibited liver progenitor cell characteristics similar to the gp38(-)CD133(+) population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis. PMID- 26564720 TI - Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-alpha regulation. AB - While the intestine plays an important role in digestion and absorption, the mucus lining the epithelium represents a pivotal function in mucosal protection. Goblet cells are scattered in both the crypts and among enterocytes, and they secrete an important component of mucus, mucin. We have reported that sodium/hydrogen exchanger (NHE) 8 is a novel player in mucosal protection, since loss of NHE8 function resulted in reduced mucin production and increased bacterial adhesion. While NHE8 has been shown to be expressed in enterocytes and its expression is reduced during intestinal inflammation, nothing is known about the role of NHE8 in goblet cells. This current study is designed to define the expression of NHE8 and the role of TNF-alpha in the regulation of NHE8 in goblet cells. Using HT29-MTX cells as an in vitro model, we detected abundant NHE8 mRNA in goblet cells. Immunohistochemical staining localized NHE8 protein on the plasma membrane and in the intracellular compartments in goblet cells. Furthermore, NHE8 expression in goblet cells is regulated by the proinflammatory cytokine TNF-alpha. The expression of NHE8 in HT29-MTX cells was significantly reduced at both mRNA and protein levels in the presence of TNF-alpha. This inhibition of NHE8 mRNA expression could be blocked by the transcriptional inhibitor actinomycin D. Promoter reporter assay showed that NHE8 promoter activity was indeed reduced by TNF-alpha. Mechanistically, TNF-alpha reduced Sp3 protein binding to the human NHE8 basal promoter region. Therefore, NHE8 is expressed in goblet cells, and the inflammatory cytokine TNF-alpha downregulates NHE8 expression by a transcriptional mechanism. PMID- 26564721 TI - Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis. AB - Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine. PMID- 26564719 TI - Mechanisms of the adenosine A2A receptor-induced sensitization of esophageal C fibers. AB - Clinical studies indicate that adenosine contributes to esophageal mechanical hypersensitivity in some patients with pain originating in the esophagus. We have previously reported that the esophageal vagal nodose C fibers express the adenosine A2A receptor. Here we addressed the hypothesis that stimulation of the adenosine A2A receptor induces mechanical sensitization of esophageal C fibers by a mechanism involving transient receptor potential A1 (TRPA1). Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A2A receptor selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10-60 mmHg) in a concentration-dependent fashion (1-100 nM). At the half-maximally effective concentration (EC50: ~3 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A2A antagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist alpha,beta-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031. Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A2A-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A2A receptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1. PMID- 26564722 TI - Osteoid osteoma of the foot and ankle--A systematic review. AB - BACKGROUND: Osteoid osteomas are responsible for 10% of benign bone tumours. Treatment typically involves surgical excision or radio frequency ablation. The aim of this systematic review is to evaluate reported cases of foot and ankle osteoid osteomas. METHODS: We conducted a systematic review of the literature using the online databases Medline and EMBASE. We included studies reporting osteoid osteoma diagnosed either radiologically or histologically. RESULTS: 94 studies were included reporting 223 cases; 70.5% were male, mean age was 23 years, 69% reported night pain and 72% responded to NSAIDs. The commonest affected bone was the talus. CT scan was the most useful radiological investigation and MRI missed the diagnosis in 34% of cases. The majority of patients underwent surgical excision but an increasing trend of ablation therapy was demonstrated. CONCLUSIONS: A high index of suspicion based on salient history and appropriate imaging are essential for timely identification and treatment. PMID- 26564723 TI - Dual plating with bone block arthrodesis of the first metatarsophalangeal joint: A clinical retrospective review. AB - BACKGROUND: First metatarsal phalangeal joint (MTP) arthrodesis is challenging in the setting of bone loss. The purpose of this study was to describe the results of interpositional grafting and arthrodesis of the first MTP joint using two plates in a 90/90 configuration. MATERIALS AND METHODS: Eleven patients had an MTP arthrodesis with 90-90 plating with an interpositional allograft. We analyzed the fusion rate, restoration of first ray length, patient satisfaction, and complication rates. RESULTS: The overall union rate was 90.9%, with an average restoration of 11 +/- 4.5mm in length to the first ray. The average time to fusion was 10.7 +/- 1 weeks. The mean preoperative AOFAS score improved significantly. The complication rate was 18.2% and included one superficial wound infection and one non-union who underwent a successful fusion after revision. CONCLUSION: Arthrodesis of the first MTP joint with two 90/90 plates and restoration of length using an interpositional graft has excellent patient satisfaction and functional outcomes. PMID- 26564724 TI - The use of the 4.5 mm 90 degrees titanium cannulated LC-angled blade plate in tibiotalocalcaneal and complex ankle arthrodesis. AB - BACKGROUND: Tibiotalocalcaneal arthrodesis is used to manage end stage arthritis, often associated with severe bone loss. The goal is to relieve pain through a stable, well-aligned hindfoot and ankle. We describe our initial results and outcome of ankle and tibiotalocalcaneal arthrodesis using a 90 degrees blade plate. METHODS: We retrospectively reviewed the records of patients managed at our institution between 2010 and 2014. Twenty cases were identified who had either talocrural (n = 9) or TTC fusion (n = 11) with 1 patient having both ankle and then TTC fusion in separate sittings. RESULTS: Fusion occurred in 18 of the 20 cases (90%) with correction of angular deformity and restoration of hindfoot alignment. None of the 18 patients developed complications and all discharged to follow-up when independently mobile and satisfied with the outcome. CONCLUSIONS: This study demonstrated that using a 90 degrees blade plate for ankle or TTC arthrodesis in a diverse group of complex primary and revision indications associated with severe deformity and bone loss resulted in a high rate of bony union and stable deformity correction. PMID- 26564725 TI - Radiographic monitoring of the distal insertion of the calcaneofibular ligament in anatomical reconstructions of ankle instabilities: A preliminary cadaveric study. AB - BACKGROUND: The purpose of the study therefore was to determine radiographic landmarks that support the identification of the insertion site of the distal calcaneofibular ligament (CFL) in anatomic ankle ligament reconstructions. METHODS: In 10 lower limb cadaver specimens the midpoint of the distal CFL insertion was dissected and marked with a nail inserted orthogonally. On a standardized lateral radiograph in neutral ankle position a horizontal tangent was aligned to the deepest visible concavity of the tarsal sinus and one vertical tangent to the farthest posterior convexity of the talus. Additionally, a line was drawn from the radiographically marked distal CFL to the fibular insertion of the CFL to determine the CFL-fibular angle. RESULTS: In relation to the radiographic tangents intersection the mean deviation of the depicted CFL nails was 2.2mm [SD +/- 1.1 mm] leading to an angular, circular to slightly oval 6 mm insertion. The scatter-plot of the marked positions convened along a line from the supposed fibular CFL insertion to the intersection in all cases. The mean CFL fibular angle was 131.7 degrees [SD +/- 3.16 degrees ]. CONCLUSIONS: Determining a virtual intersection between a horizontal tangent aligned to the deepest visible concavity of the tarsal sinus and one vertical tangent aligned to the farthest posterior convexity of the talus on a standardized lateral radiograph in neutral ankle position supports an anatomic insertion of the distal calcaneofibular ligament most probably. PMID- 26564727 TI - Incidence and recognition of peroneal tendon dislocation associated with calcaneal fractures. AB - BACKGROUND: Questions abound regarding natural history and medicolegal implications of untreated peroneal tendon dislocation (PTD) associated with calcaneal fractures. METHODS: We retrospectively analyzed CT scans and anteroposterior ankle radiographs of 79 consecutive calcaneal fractures presenting over 4 years at a single institution. RESULTS: Nineteen patients (24%) had associated PTD, which was initially missed in 10 (53%). Bony fleck was present in 11 (13.75%). Soft tissue swelling at lateral malleolar level, present on radiographs of 18 tendon dislocators (95%), raises likelihood of PTD with increasing specificity the greater the swelling. In 6 patients, surgeons failed to identify on CT spontaneously relocated tendons that then peeped around the posterolateral fibula, a finding not appreciable on 3-dimensional volume rendering. CONCLUSIONS: Despite a significant association of PTD with calcaneal fractures, it still passes unrecognized all too frequently. Anatomical fracture fixation does not guarantee stable tendon reposition. Further studies are required to elucidate functional outcome of untreated PTD. PMID- 26564726 TI - Operative versus nonoperative treatment of acute Achilles tendon rupture: An analysis of 12,570 patients in a large healthcare database. AB - BACKGROUND: The purpose of this study was to compare the latest patient demographics and rerupture rates of operative versus nonoperative treatment of acute Achilles tendon rupture in the United States. METHODS: Patients undergoing treatment of an acute Achilles tendon rupture from 2007 to 2011 were identified by cross-referencing ICD-9-CM and CPT codes through the PearlDiver Patient Record Database. RESULTS: In total, 12,570 patients were treated for an acute Achilles tendon rupture. The ratio of operative to nonoperative treatment increased from 1.41 to 1.65. Males were more likely to undergo surgery than females. There were no significant differences in short-term rerupture rate for operative (2.1%) versus nonoperative (2.4%) treatment. CONCLUSIONS: The proportion of patients who received operative treatment for an acute Achilles tendon rupture increased slightly during the 5 year period, suggesting that surgeons in the United States have been slower to adopt nonoperative treatment than their European counterparts. PMID- 26564728 TI - Sport and activity restrictions following total ankle replacement: A survey of orthopaedic foot and ankle specialists. AB - BACKGROUND: Despite an increasing utilization of total ankle replacement, surgeons have little guidance with regards to physical activity and sport participation recommendations following the procedure. METHODS: Orthopaedic foot and ankle specialists were surveyed as to the activity and sports restrictions they place on their patients following ankle replacement. Fifty sports and activities were included and the results were used to derive a set of consensus recommendations. Of the 1063 surgeons that were sent the survey, 173 responded, yielding a response rate of 16.3%. RESULTS: In general, surgeons were comfortable with aerobic or low impact sports and activities. Boot immobilized sports represented a grey area with the determination of whether or not to allow them based largely on the prior experience of the patient. High impact, cutting and jumping sports and activities were largely discouraged. Young age, high BMI and poor bone quality led surgeons to be more restrictive. CONCLUSIONS: These consensus recommendations serve as a useful guideline for surgeons and help patients set appropriate expectations for the procedure. PMID- 26564729 TI - Oral thromboprophylaxis in patients with ankle fractures immobilized in a below the knee cast. AB - BACKGROUND: Lower-limb immobilization has been implicated as an etiologic factor for a venous thromboembolism (VTE). Most of the current literature encourages the use of thromboprophylaxis with injectable low-molecular-weight heparin (LMWH) in trauma patients. Injectable anticoagulants have inherent problems of producing pain and bruising. They are also difficult to administer, leading to low compliance. Oral anticoagulants are therefore gaining popularity for use as thromboprophylactic agents in hip and knee arthroplasty patients. There are not enough studies in the literature, however, to support their use in ambulatory trauma patients whose ankle fractures are being managed nonoperatively on an outpatient basis. METHODS: This study evaluated the efficacy of oral anticoagulants for preventing VTE in ambulatory trauma patients who required temporary lower limb immobilization for non-operative management of their ankle fractures. A total of 200 consecutive patients who presented to the fracture clinic with an ankle fracture that was managed in a plaster cast were included in this study. These patients were assessed for risk of developing VTE and high risk patients were administered an oral anticoagulant to prevent VTE. RESULTS: There was only one case of an isolated distal DVT among the 200 patients. CONCLUSIONS: This study shows that an oral anticoagulant was a safe alternative to injectable LMWH as a thromboprophylactic agent for ambulatory trauma patients requiring temporary lower limb immobilization for non-operative management of an ankle fracture. PMID- 26564730 TI - Intramedullary fixation in severe Charcot osteo-neuroarthropathy with foot deformity results in adequate correction without loss of correction - Results from a multi-centre study. AB - BACKGROUND: Charcot osteo-neuroarthropathy (CN) of the foot can induce severe instability and deformity. Results of a consecutive clinical multi-centre study with Midfoot Fusion Bolt (MFB, Synthes GmbH, Oberdorf, Switzerland) are reported. METHODS: All patients (aged 18 years and older) treated between 2009 and 2013 with surgical reconstruction of the midfoot with MFB for CN were included. Demographics, pre-surgical health status, details of foot pathology, details of surgery, postoperative treatment, treatment failure, and adverse events were registered. The following radiographic angles were measured on pre-op, post-op and last follow-up radiographs: talo-1st metatarsal (TMT) angle dorsoplantar and lateral view, and calcaneo-5th metatarsal angle. RESULTS: Forty-seven patients (48 feet) were included in three centres. In 38 patients (80.1%) diabetes was diagnosed. Wound healing problems occurred in 21% of patients and recurrent ulceration in 13%. Revision surgery for loss of correction was performed in three cases (6%). Union rate at final follow-up was 98%. Major amputation for deep infection was performed in two patients (4%), minor amputation at the foot level in three cases (6%). Failure was more frequent when only one MFB (instead of 2 or 3) was used and no Gastrocnemius lengthening was performed. Radiographic alignment significantly improved pre- versus postoperatively and preoperatively versus follow-up. CONCLUSIONS: Realignment and fixation with MFB in severe CN result in adequate correction with minimal loss of correction in the observed clinical course. The non-union rate was lower than previously reported. Stable fixation with MFB is a valuable treatment option for CN with minimal loss of correction and high union rates. The use of a minimum of two bolts is recommended to avoid recurrent deformity. Clinical Trials.gov: NCT01770639. PMID- 26564731 TI - There is poor reliability of Bohler's angle and the crucial angle of Gissane in assessing displaced intra-articular calcaneal fractures. AB - BACKGROUND: Two-dimensional measurements are used to describe displaced intra articular calcaneal fractures (DIACF). Our study evaluates the performance of Bohler's angle (BA) and the crucial angle of Gissane (CAG) among orthopedic surgeons. METHODS: Thirty-four pre- and post-operative lateral foot radiographs from patients with DIACF were shown to four orthopedic surgeons who measured BA and the CAG. The intra- and inter-observer reliability were calculated using the intra-class correlation coefficient (ICC). Additionally, we calculated frequency of consensus given an allowed discrepancy. We then determined the tolerance limit for each measurement. RESULTS: The ICC for inter-observer reliability of BA was 0.83 in the first session and 0.77 in the second. The ICC for intra-observer reliability ranged from 0.83 to 0.98. For the CAG, the inter-observer ICC was 0.28 and 0.1 in the two sessions. Intra-observer ICC ranged from 0.16 to 0.67. With an allowed discrepancy of 20 degrees , there was lack of consensus for BA in 37.5% and for the CAG in 59% of measurements on average. The 95% confidence interval for 90% agreement in BA involved a range of 76 degrees . For CAG, the 95% confidence interval of tolerance for 90% agreement was 56 degrees . CONCLUSIONS: For BA and CAG, there is frequent disagreement among experienced observers, even given a wide tolerance range. We recommend use of caution when applying BA as currently measured in making treatment decisions for DIACF. LEVEL OF CLINICAL EVIDENCE: Diagnostic, level III. PMID- 26564732 TI - Use of peripheral blocks and tourniquets in foot surgery: A survey of Australian orthopaedic foot and ankle surgeons. AB - BACKGROUND: The most common reasons for unplanned admission to the hospital from outpatient surgery have the potential to be minimised or eliminated by peripheral nerve blocks (PNB). Tourniquets are commonly used in elective extremity surgery but it's use is mostly guided by personal preferences and does no correlate with the existing literature. Our aim was to explore the current practice of PNB and tourniquet use by foot and ankle surgeons in Australia. METHODS: The Australian Orthopaedic Foot and Ankle Surgery Society (AOFAS) annual meeting was held in Adelaide in 2011. Members were asked to complete an electronic survey on their current use of peripheral nerve blocks and tourniquets. Two specific elective case scenarios were included for comment, one pertaining to forefoot pathology, the other hindfoot pathology. RESULTS: Twenty-three AOFAS members replied to the survey, an overall response rate of 76.6%. Of these, only two surgeons did not use ankle blocks in elective surgery and none were prepared to operate without a tourniquet. Most Australian foot and ankle surgeons were reluctant to use local anaesthetic techniques without an accompanying GA. CONCLUSIONS: While the literature suggests that GA may add to complications without any benefit for the procedure and that distally based tourniquets may add benefit, these are not the favoured techniques in Australian foot and ankle surgeons. PMID- 26564733 TI - Surgery for adult acquired flatfoot due to posterior tibial tendon dysfunction reduces pain, improves function and health related quality of life. AB - BACKGROUND: Patients with adult acquired flatfoot deformity (AAFD) due to posterior tibial tendon dysfunction (PTTD) may require surgery but few reports have evaluated the outcome. METHODS: We evaluated 21 patients with a median age of 60 (range 37-72) years who underwent different surgical reconstructions due to stage II AAFD before and 6 and 24 months after surgery by the validated Self Reported Foot and Ankle Score (SEFAS), Short Form 36 (SF-36) and Euroquol 5 Dimensions (EQ-5D). RESULTS: The improvement from before to 24 months after surgery was in SEFAS mean 12 (95% confidence interval 8-15), SF-36 physical function 21 (10-22), SF-36 bodily pain 28 (17-38), EQ-5D 0.2 (0.1-0.3) and EQ-VAS 11 (2-21). CONCLUSION: Surgery for AFFD due to PTTD results in reduced pain and improved function and health related quality of life. The outcome scores have been demonstrated as useful. It has also been shown, since there is a further improvement between 6 and 24 months after surgery, that a minimum follow-up of 2 years is needed. LEVEL OF CLINICAL EVIDENCE: III - prospective observational cohort study. PMID- 26564734 TI - The value of Weight-Bearing CT scan in the evaluation of subtalar distraction bone block arthrodesis: Case report. AB - Subtalar distraction arthrodesis is performed in certain situations where there is loss of subtalar height, reduced talar declination and evidence of anterior tibiotalar impingement. Standard evaluation includes the assessment of the lateral talocalcaneal angle, calcaneal pitch, talocalcaneal height and talar declination angle on a weight bearing lateral radiograph. We present a case of erosive valgus subtalar osteoarthritis with subtalar collapse managed with a subtalar distraction arthrodesis. A weight bearing CT (WB-CT) scan was used in the assessment. The value of WB-CT for this indication is discussed, along with a discussion on surgical technique, complications and future directions. PMID- 26564735 TI - Giant cell tumour of tendon sheath with simultaneous two tendon involvement of the foot treated with excision of the tumour and reconstruction of the flexor retinaculum using tibialis posterior tendon in a paediatric patient: A rare case report. AB - Giant cell tumour of tendon sheath is a benign soft tissue tumour arising from the tendon sheath. The involvement of foot and ankle by such tumours is relatively rare. Children are not commonly afflicted by this condition. All such tumours are reported to arise either from a single tendon sheath or one joint. We report a case of giant cell tumour of tendon sheath in a 12-year-old child, arising simultaneously from the tendon sheaths of tibialis posterior and flexor digitorum longus tendons, as well as extending into the ankle joint. It was treated by complete excision of the mass along with the tendon sheaths with reconstruction of the flexor retinaculum. The location of the tumour, age of the patient, diffuse nature of the tumour and novel technique of reconstruction of the flexor retinaculum make this case extremely rare and the first to be reported in literature. PMID- 26564737 TI - Development and Validation of an UPLC-Q-TOF-MS Method for Quantification of Fuziline in Beagle Dog After Intragastric and Intravenous Administration. AB - A specific and sensitive UPLC-Q-TOF-MS method operated in the positive ion mode was developed and validated for the quantification of Fuziline in Beagle dog plasma. Fuziline and Neoline internal standard were separated on an Acquity UPLC BEH C18 column with the total running time of 4 min using gradient elution at the flow rate of 0.25 mL/min. The calibration curves for Fuziline showed good linearity in the concentrations ranging from 2 to 400 ng/mL with correlation coefficients (r) greater than 0.9971. The lower limit of quantification was 0.8 ng/mL. Intra- and interbatch relative standard deviations ranged from 2.11 to 3.11% and 3.12 to 3.81%, respectively. Fuziline was stable under different sample storage and processing conditions. The developed method was successfully applied to the comparative pharmacokinetic study of Fuziline in Beagle dog after intravenous and oral administration. Low absolute bioavailability of Fuziline (1.45 +/- 0.76%) suggested a significant metabolism transformation extent in Beagle dog. PMID- 26564736 TI - The sweet side of RNA regulation: glyceraldehyde-3-phosphate dehydrogenase as a noncanonical RNA-binding protein. AB - The glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has a vast array of extraglycolytic cellular functions, including interactions with nucleic acids. GAPDH has been implicated in the translocation of transfer RNA (tRNA), the regulation of cellular messenger RNA (mRNA) stability and translation, as well as the regulation of replication and gene expression of many single-stranded RNA viruses. A growing body of evidence supports GAPDH-RNA interactions serving as part of a larger coordination between intermediary metabolism and RNA biogenesis. Despite the established role of GAPDH in nucleic acid regulation, it is still unclear how and where GAPDH binds to its RNA targets, highlighted by the absence of any conserved RNA-binding sequences. This review will summarize our current understanding of GAPDH-mediated regulation of RNA function. WIREs RNA 2016, 7:53-70. doi: 10.1002/wrna.1315 For further resources related to this article, please visit the WIREs website. PMID- 26564739 TI - [Biosafety evaluation: an important field of studies on human embryonic stem cell]. PMID- 26564740 TI - [Expert consensus on the methods of differentiation of human embryonic stem cell into epidermal keratinocytes]. PMID- 26564738 TI - Absence of DAB2IP promotes cancer stem cell like signatures and indicates poor survival outcome in colorectal cancer. AB - Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic colonization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC. We demonstrate that DAB2IP suppresses NF kappaB-mediated EMT and CSC features in CRC cells. In DAB2IP knockout mice, we discovered the hyperplasia in colonic epithelium which aberrantly represents the mesenchymal feature and NF-kappaB pathway activation. In clinic CRC tissue, we also reveal that reduced DAB2IP can enrich the CD133(+) subpopulation. DAB2IP expression was inversely correlated with tumor differentiation and metastasis, and patients with lower DAB2IP expression had shorter overall survival time. Taken together, our study demonstrates that DAB2IP inhibits NF-kappaB-inducing EMT and CSC to suppress the CRC progression, and also suggests that DAB2IP is a beneficial prediction factor for CRC patient prognosis. PMID- 26564741 TI - [Circadian rhythm variation of the clock genes Per1 and cell cycle related genes in different stages of carcinogenesis of buccal mucosa in animal model]. AB - OBJECTIVE: To investigate the expression and circadian rhythm variation of biological clock gene Per1 and cell cycle genes p53, CyclinD1, cyclin-dependent kinases (CDK1), CyclinB1 in different stages of carcinogenesis in buccal mucosa and its relationship with the development of buccal mucosa carcinoma. METHODS: Ninety golden hamsters were housed under 12 hours light-12 hours dark cycles, and the model of buccal squamous cell carcinoma was established by using the dimethylbenzanthracene (DMBA) to smear the golden hamster buccal mucosa. Before the DMBA was used and after DMBA was used 6 weeks and 14 weeks respectively, the golden hamsters were sacrificed at 6 different time points (5 rats per time point) within 24 hour, including 4, 8, 12, 16, 20 and 24 hour after lights onset (HALO), and the normal buccal mucosa, precancerous lesions and cancer tissue were obtained, respectively. HE stained sections were prepared to observe the canceration of each tissue. Real time RT-PCR was used to detect the mRNA expression of Per1, p53, CyclinD1, CDK1 and CyclinB1, and a cosine analysis method was applied to determine the circadian rhythm variation of Per1, p53, CyclinD1, CDK1 and CyclinB1 mRNA expression, which were characterized by median, amplitude and acrophase. RESULTS: The expression of Per1, p53, CDK1 and CyclinD1 mRNA in 6 different time points within 24 hours in the tissues of three different stages of carcinogenesis had circadian rhythm, respectively. However, the CyclinB1 mRNA was expressed with circadian rhythm just in normal and cancer tissue (P < 0.05), while in precancerous lesions the circadian rhythm was in disorder (P > 0.05). As the development of carcinoma, the median of Per1 and p53 mRNA expression were significantly decreased (P < 0.05), yet the median of CDK1, CyclinB1 and CyclinD1 mRNA expression were significantly increased (P < 0.05). The amplitude of Per1, p53 and CyclinD1 mRNA expression was significantly decreased as the development of carcinoma (P < 0.05), however the amplitude of CDK1 mRNA expression was significantly increased (P < 0.05). In addition, there was no significant difference in the amplitude of CyclinB1 mRNA expression. The time that the peak expression value of Per1 and CDK1 mRNA appeared (Acrophase) in precancerous lesions was remarkably earlier than that in normal tissues, but the acrophase of p53 and CyclinD1 mRNA expression was remarkably delayed. Moreover, the acrophase of CDK1 and CyclinB1 mRNA expression in cancer tissues was obviously earlier than that in normal tissues, yet there was no significant variation in acrophase of Per1, p53, CyclinD1 mRNA expression between normal tissues and cancer tissues. CONCLUSIONS: The circadian rhythm of clock gene Per1 and cell cycle genes p53, CyclinD1, CDK1, CyclinB1 expression remarkably varied with the occurrence and development of carcinoma. Further research into the interaction between circadian and cell cycle of two cycle activity and relationship with the carcinogenesis may providenew ideas and methods of individual treatment and the mechanism of carcinogenesis. PMID- 26564742 TI - [The influence of zoledronic acid on vascular endothelial cell]. AB - OBJECTIVE: To investigate the influence of zoledronic acid on vascular endothelial cells. METHODS: The influence of zoledronic acid on proliferation, migration and adhesion of vascular endothelial cells were tested with 3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell migration assay and cell adhesion assay. The results of each experimental group were compared with the control group and the data statistically analyzed. RESULTS: In a concentration of 0-0.5 mmol/L, the absorbance value decreased from 0.09 to 0.34 as the drug concentration increased. Scratch test showed that the change of width of scratch before and after 24 hours in control, low, medium and high concentration groups were (38.7 +/- 0.42), (35.8 +/- 4.17), (19.9 +/- 0.57) mm (P < 0.001), (12.5 +/- 3.89) mm (P < 0.05). Adhesion test showed that the absorbance value in control, low, medium and high concentration groups were 1.14 +/- 0.18, 0.95 +/- 0.13, 0.81 +/- 0.11 (P < 0.01), 0.67 +/- 0.19 (P < 0.001). Comparisons between control and experimental groups were analyzed by t-test and P values < 0.05 were considered statistically significant. CONCLUSIONS: Zoledronic acid inhibits the proliferation, migration and adhesion of vascular endothelial cells. PMID- 26564743 TI - [Cone-beam CT evaluation of nasomaxillary complex and upper airway following rapid maxillary expansion]. AB - OBJECTIVES: To evaluate the naso-maxillary complex width and pharyngeal airway volume changes after rapid maxillary expansion (RME). METHODS: Thirty-five patients were selected (18 males, 17 females, mean age, 12.1 +/- 1.1 years). All patients underwent orthodontic treatment with Hyrax palatal expanders. Cone-beam CT (CBCT) scan was taken before treatment (T0), 16 days (T1) and three months (T3) after RME. Naso-maxillary complex width and pharyngeal airway volume were measured. RESULTS: After treatment the width of piriform aperture and maxillary width were significantly increased compared with that before treatment (P < 0.05). Three months after RME, no statistical difference was found in maxillary width compared with that before treatment. The nasopharyngeal volume significantly increased by 29.9% compared with that before treatment (P < 0.05), and the volume remained relatively stable after three months. CONCLUSIONS: RME resulted in a significant increase in the naso-maxillary complex width and nasopharyngeal volume. PMID- 26564744 TI - [Effect of Lactobacillus acidophilus on metabolizing lactic acid in formula milk: a quantitative analysis of the effect of erythritol]. AB - OBJECTIVE: To evaluate the lactic acid productivity of Lactobacillus acidophilus (La) exposed to formula milk containing different concentration of erythritol. METHODS: La was cultured under anaerobic condition (80% N(2), 10% CO(2), 10% H(2)) at 37 degrees C in five experimental groups (formula milk mixed with different concentrations of erythritol). The five experimental groups contained 1%, 2%, 4%, 6%, and 8% erythritol, respectively (groups 1% E-M, 2% E-M, 4% E-M, 6% E-M, 8% E-M). Formula milk served as control group (group M). The lactic acid was analyzed by high performance liquid chromatography (HPLC) at 4 h intervals during 24 h. The peak-area of lactic acid was recorded and used to calculate the concentration of lactic acid through the equation of a standard curve (y = 590 244x + 67 507). ANOVA and Tukey HDS analysis were used to analyze the data. RESULTS: The concentration of lactic acid at 24 h was group M [(4.693 +/- 0.105) g/L], group 1% E-M[(4.114 +/- 0.186) g/L], group 2% E-M[(3.720 +/- 0.158) g/L], group 4% E-M[(3.045 +/- 0.152) g/L], group 6% E-M[(2.971 +/- 0.086) g/L], group 8% E-M[(2.789 +/- 0.142) g/L]. Statistically significant differences in lactic acid concentrations were found between different time points (P < 0.05) and between different groups (F = 187.448, P < 0.05). Moreover, the concentrations of lactic acid in each experimental group was lower than that in control group (P < 0.05). The difference among groups 4% E-M, 6% E-M, and 8% E-M were not statistically significant (P > 0.05). CONCLUSIONS: Erythritol showed the inhibition potential against La in metabolizing lactic acid in formula milk. The effect of erythritol was concentration depended. The higher concentration of erythritol contained in the milk, the better the inhibition potential against La in metabolizing lactic acid. PMID- 26564745 TI - [Antibacterial effect of the carboxymethyl chitosan zinc peptide on several periodontal pathogens in vitro]. AB - OBJECTIVE: To determine the antimicrobial effects of carboxymethyl chitosan zinc (CMC-Zn(+)) and CMC-Zn(+)-peptide (CMC-Zn(+)-P) on four kinds of periodontal pathogens. METHODS: Dilution method was used to determine the minimum inhibitory concentration (MIC) of CMC-Zn(+) for Porphyromonas gingivalis (Pg), Actinobacillusactinomycetemcomitans (Aa), Prevotella intermedia (Pi) and Actinomyces viscosus (Av). The antimicrobial characters of CMC-Zn(+) and CMC Zn(+)-P on these four kinds of pathogens were evaluated by disk diffusion method. RESULTS: The MIC of CMC-Zn(+) for Pg, Aa, Pi and Av was 0.312 5%, 0.156 25%, 0.156 25% and 0.078 125% respectively. Significant antimicrobial effects were improved along with the increased concentration of CMC-Zn(+) and CMC-Zn(+)-P (P < 0.01), while the best antimicrobial concentrations of both CMC-Zn(+) and CMC Zn(+)-P were 5%. The antimicrobial effect of CMC-Zn(+)-P was better than that of CMC-Zn(+) on the same kind of periodontal pathogen (P < 0.01). CMC-Zn(+)-P showed different antimicrobial effects on the four periodontal pathogens (Av > Aa > Pi or Av > Aa > Pg, P < 0.01). CONCLUSIONS: CMC-Zn(+) and CMC-Zn(+)-P have inhibition effect on Pg, Aa, Pi and Av, and the best antibacterial concentration was 5%. The CMC-Zn(+)-P has better antibacterial effect than CMC-Zn(+) on Pg, Aa, Pi and Av. PMID- 26564746 TI - [Effect of local application of insulin like growth factor-1 gelatin sponge complex on osseointegration around implant in osteoporosis rats]. AB - OBJECTIVE: To investigate the effects of local application of insulin like growth factor-1 (IGF-1) absorbable gelatin sponge complex in implant fossa on osseointegration around implant in osteoporosis rats. METHODS: Female SD rats, aged 4 months, were randomly individed into ovariectomy group (OVX group) and sham-ovariectomy group (sham-ovx group). The rats in OVX group (n = 15) were ovariectomized, and the rats in Sham-OVX group (n = 10) underwent Sham ovariectomy. Eight weeks later, 5 rats in each group were randomly selected to confirm the osteoporosis model. The ovariectomized rats were randomly divided into osteoporosis group (OP group) and IGF-1 group after the model was successfully established, 5 rats in each group. Pure titanium implants were implanted in the distal part of right femoral epiphyseal in all groups. Absorbable gelatin sponge particles containing 10 ug IGF-1 were placed in the planting fossa in the IGF-1 group, and absorbable gelatin sponge particles without IGF-1 were used in OP group and sham-OVX group. The rats were sacrificed, and then the distal part of right and left femoral epiphyses were taken out to make undecalcified and decalcified tissue sections respectively after 8 weeks. Combined bone lamella width (CBLW) and implant bone contact rate (IBCR) around implant, trabecular width (TW) and trabecular area percentage (TA) around implant and in the cortical bone of left femoral epiphyses were observed by histomorphometric measurement. RESULTS: The CBLW, IBCR, TW and TA around implant was (55.43 +/- 3.50) um, (81.79 +/- 4.45) %, (57.73 +/- 4.29) um and (62.21 +/- 7.42) % respectively in sham-OVX group, (60.22 +/- 4.70) um, (83.67 +/- 6.63) %, (48.08 +/- 3.63) um and (58.20 +/- 8.93) % respectively in IGF-1 group, and (37.11 +/- 2.18) um, (64.60 +/- 5.44) %, (41.19 +/- 2.93) um and (42.21 +/- 4.34) % respectively in OP group. The CBLW, IBCR and TW around implant had no differences between IGF-1 and sham-OVX group (P > 0.05), which were significantly higher than those in OP group (P < 0.05). The TW and TA of cortical bone in left distal femoral epiphyses was (60.85 +/- 6.64) um, (61.24 +/- 6.98) % respectively in sham-OVX group, (38.68 +/- 4.74) um, (43.89 +/- 7.76) % respectively IGF-1 group, (40.46 +/- 5.38) um, (44.63 +/- 5.39) % respectively in OP group (P < 0.05). The TW and TA of cortical bone in left distal femoral epiphyses had no differences between IGF-1 group and OP group (P > 0.05), which were all significantly lower than those in sham-OVX group (P < 0.05). CONCLUSIONS: The local application of IGF-1 gelatin sponge complex can increase bone tissue around implant and improve osseointegration in osteoporosis. PMID- 26564747 TI - [Preliminary study on transdermal characteristics and sunface anesthetic effects of lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome in animals]. AB - OBJECTIVE: To prepare a new dental topical anesthetics, lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome (LID-TAT N), and to evaluate its transdermal properties and topical anesthesia effects. METHODS: LID-TAT-N was prepared using reverse-phase evaporation method, and lidocaine loaded conventional liposome (LID-CL) was prepared in the same manner as positive control. The diameter, zeta potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured. The skin permeation of LID-TAT-N was examined, and compared with LID-CL and lidocaine injection (LID-IJ, as negative control), using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours. Each experiment was repeated six times. The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits. RESULTS: The mean diameter of LID-TAT-N was smaller than that of LID-CL [(152.7 +/- 10.6) nm vs. (259.5 +/- 15.5) nm, P < 0.01]. The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group [(1 340.0 +/- 97.5) ug . cm(-2)] than those of LID-CL and LID-IJ groups [(1 060.6 +/- 80.2), (282.6 +/- 65.1) ug . cm( 2), respectively, P < 0.05]. Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia [(24.8 +/- 2.8) min] was also longer than that of LID-IJ [(14.5 +/- 2.3) min, P < 0.05]. CONCLUSIONS: LID-TAT-N had good transdermal ability, and the advanced skin penetration feature can improve its tropical anesthetic effect. PMID- 26564748 TI - [Effect of ultraviolet-photofunctionalization of titanium on protein adsorption and competition]. AB - OBJECTIVE: To study the adsorption behavior of bovine serum albumin (BSA) and fibrinogen (Fg) and the competition of them on titanium before and after ultraviolet (UV)-photofunctionalization, and to provide the evidence of photofunctionalization on the surface modification of titanium implants. METHODS: Titanium disks and sensors of quartz crystal microbalance-D (QCM-D) were stored and sealed in the dark for 4 weeks before being divided into two groups, namely the UV-treated group and control group. Samples in the UV-treated group were treated with UV rays for 48 hours. Then the Fg adsorbing property of disks in both groups was tested at 1, 12 and 24 h. Protein films of Fg and BSA formed on QCM sensors after 1 h incubation were imaged via atomic force microscopy (AFM). Then with QCM-D, for both surfaces the adsorption of Fg and BSA as well as the competition between them was tested by introducing proteins with different sequences. RESULTS: After being incubated for 1 and 12 h, UV-treated group attracted more Fg[(0.250 +/- 0.005) and (0.172 +/- 0.006) mg] than control group did [(0.207 +/- 0.004) and (0.144 +/- 0.004) mg] (P < 0.05). However, after 24 h incubation, Fg residual on the UV-treated group [(0.080 +/- 0.003) mg] was smaller than that in the control group [(0.127 +/- 0.004) mg] (P < 0.05). AFM showed protein clustered more densely on UV-treated surfaces than control surfaces and QCM displayed the same result. In addition, when Fg was introduced into QCM-D after BSA, the mass of protein film increased on both surfaces. However, when BSA was introduced after Fg, the mass of protein film on the control group had no change, but slightly decrease on the UV-treated group. CONCLUSIONS: UV-photofunctionalization promotes protein adsorption but has no influence on the competition between Fg and BSA. PMID- 26564749 TI - [Effect of TiO2-SiO2-SnOx film with different firing temperatures on bond strength of low-fusing dental porcelain to pure titanium]. AB - OBJECTIVE: To evaluate the influence of TiO(2)-SiO(2)-SnOx nano-coatings with different firing temperatures on the bond strength of low-fusing dental porcelain to pure titanium. METHODS: The surface of pure titanium was coated uniformly with TiO(2)-SiO(2)-SnOx nano-coatings by solution-gelatin (Sol-Gel) technology and then fired at 300 degrees C (group A) or 750 degrees C (group B) for 1 h. The specimens without any coatings were the control group (group C). There were 10 specimens in each group. Dental porcelain was sintered on the surface of titanium specimens. Surface roughness and contact angle of the coatings were also detected. The titanium-porcelain bond strength was investigated according to YY 0621-2008 standards using three-point flexure bond test. The phase composition of the TiO(2)-SiO(2)-SnOx nano-coatings was characterized by X-ray diffraction(XRD). The interface of titanium-porcelain and TiO(2)-SiO(2)-SnOx nano-coatings were observed using scanning electron microscope (SEM). RESULTS: No rutile phase was found in these specimens of group A and group B. The surface roughness of group A, B, C was (0.97 +/- 0.06), (0.99 +/- 0.03), (0.96 +/- 0.07) um, respectively. No significant difference was found among the three groups. Compared with that of group C (64.37 degrees +/- 3.01 degrees ), contact angles detected in group A (52.04 degrees +/- 3.15 degrees ) and group B (85.27 degrees +/- 4.17 degrees ) were significantly different (P < 0.05). The bond strength of titanium-porcelain in group A [(35.66 +/- 2.65) MPa] was significantly increased compared with those in group B [(26.18 +/- 2.22) MPa] and group C [(31.66 +/- 3.52) MPa]. SEM photomicrographs of titanium-porcelain interface morphology of the specimens before porcelain sintering showed that TiO(2)-SiO(2)-SnOx nano-coatings in group A were compact and homogeneous with petty cracks and those in group B was loose and arranged disorderly. CONCLUSIONS: TiO(2)-SiO(2)-SnOx nano-coating fired at 300 degrees C is significantly effective in improving the titanium-porcelain bond strength. PMID- 26564750 TI - [Phage display peptide library for screening the peptides that specifically bind to osteoblasts cells]. AB - OBJECTIVE: To explore the experimental methods that the phage peptide library technology screening human osteoblast specificity polypeptide, which will provide the basis of the experiment of the Ti surface biolization modification. METHODS: Human calvarial osteoblasts were used as the target cells for whole-cell biopanning from a 12-mer peptide phage-display library. Cell eluent and cell lysis buffer were cultivate and count respectively after washing. Then the target cells were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence detection to authenticate the positive phage clones by human gingival fibroblast as the absorber cells. The positive phage clones were deduced by DNA sequencing. RESULTS: After four rounds of screening, twenty-two positive phage clones were found out from randomly selected phage monoclonals, whose single-strand DNA were extracted and sequenced. Amino acid sequence of the highest frequency peptide was MGWSWWPETWPM. CONCLUSIONS: The specific peptide against human osteoblasts can be obtained from a phage-display peptide library for use as a new research approach and experimental basis of the biolization modification of the titanium surface. PMID- 26564751 TI - [Genetic research strategies of oral monogenic diseases and rare diseases]. PMID- 26564752 TI - [Calcium pyrophosphate dihydrate deposition disease of the temporomandibular joint: report of 1 case]. PMID- 26564753 TI - Standardisation of a novel sperm banking kit - NextGen((r)) - to preserve sperm parameters during shipment. AB - Many male patients diagnosed with cancer are within their reproductive years. These men are advised to freeze their spermatozoa prior to the start of cancer treatment. Very often, sperm banking facilities may not be readily available and patients may be required to travel to distant sperm bank centres. Our objective was to design and standardise a remote home shipping sperm kit that allows patients to collect a semen sample at home and ship it overnight to a sperm bank. A total of 21 semen samples and two transport media (refrigeration media and human tubal fluid) and five different combinations of ice packs were tested for maintaining desired shipping temperature. Ten semen samples were assessed for pre and post-shipment changes in sperm motility, membrane integrity, total motile spermatozoa and recovery of motile spermatozoa. Even though motility, membrane integrity and total motile spermatozoa declined both in samples examined under simulated shipped conditions and in overnight-shipped samples, the observed motility and total motile spermatozoa were adequate for use with assisted reproductive techniques. Using refrigeration media, cooling sleeve and ice packs, adequate sperm motility can be maintained utilising NextGen((r)) kit and these spermatozoa can be used for procreation utilising ART techniques such as intracytoplasmic sperm injection. PMID- 26564756 TI - Looking Ahead to Atlantic City. PMID- 26564754 TI - Non-medical use of prescription pain medications and increased emergency department utilization: Results of a national survey. AB - BACKGROUND: There are no population-based studies of emergency department (ED) utilization by individuals using prescription pain medications non-medically. We examined whether non-medical use of prescription pain medications was independently associated with increased ED utilization. METHODS: We conducted a retrospective analysis of a nationally representative sample of the non institutionalized, civilian U.S. population in the National Survey on Drug Use and Health, 2008-2013. We used multivariable logistic regression to examine the association between past year ED utilization and non-medical use of prescription pain medications, defined as use of medications "not prescribed for you or that you took only for the experience or feeling they caused". RESULTS: An estimated 10.5 million adults annually reported past year non-medical use (NMU) of prescription pain medications, and 39%, or 4.1 million adults annually, also reported one or more past year ED visits. After adjustment for sociodemographic and clinical characteristics, adults with past year NMU of prescription pain medications had increased odds of past year ED utilization (adjusted odds ratio 1.32; 95% confidence interval 1.24-1.41). In secondary analyses, individuals with more frequent NMU had increased odds of ED utilization in unadjusted analyses, but this association was attenuated with adjustment for the source of prescription pain medication (i.e., physician, friend/family, other source). CONCLUSIONS: Non-medical use of prescription pain medications is associated with increased ED utilization. Further work is needed to identify the optimal role of ED settings in providing screening, education, and treatment referral for individuals using prescription pain medications non-medically. PMID- 26564757 TI - Odds Ratio Meta-Analysis and Increased Prevalence of White Matter Injury in Healthy Divers. AB - INTRODUCTION: Increased white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) brain scans of high altitude aircrew and altitude chamber workers indicate that exposure to low ambient pressure (hypobaria) promotes white matter injury. If associated with frequent decompression stress then experienced divers should also exhibit more WMH, yet published case-control studies are inconsistent. This meta-analysis evaluated the prevalence of WMH in healthy divers and controls. METHODS: Eligible studies compared experienced divers (or hyperbaric workers) without neurological decompression illness with nondiving controls, identified from multiple database searches and reference list reviews. Studies were scored for sample size, recruitment bias, control matching, MRI sensitivity, and confounding factors before grading as low, medium, or high quality. Meta-analysis of odds ratios (OR) with 95% confidence intervals (CI) was conducted on all data using a random effects model and repeated after exclusion of low-quality studies. RESULTS: There were 11 eligible studies identified. After data adjustment to exclude diving accidents, these encompassed 410 divers and 339 controls, of which 136 (33%) and 79 (23%), respectively, exhibited WMH (OR 1.925, 95% CI 1.088 to 3.405). Excluding four low-quality studies eliminated meta analysis heterogeneity, with 98 of 279 divers (35%) and 44 of 232 controls (19%) exhibiting WMH (OR 2.654, 95% CI 1.718 to 4.102). CONCLUSIONS: Results suggest that repeated hyperbaric exposure increases the prevalence of white matter injury in experienced healthy divers without neurological decompression illness. This is consistent with reports of increased WMH in asymptomatic altitude workers and an association with intensity of dysbaric exposure. PMID- 26564758 TI - Modern Air Combat Developments and Their Influence on Neck and Back Pain in F-16 Pilots. AB - INTRODUCTION: Neck and back pain in fighter pilots remains a serious occupational problem. We hypothesized that recent advances such as the joint helmet mounted cueing system (JHMCS) in modern air combat might contribute to the development of spinal complaints in F-16 pilots. METHODS: Surveyed were 59 F-16 pilots of the Royal Netherlands Air Force who were compared to 49 F-16 pilots who filled in a similar questionnaire in 2007. The prevalence of neck and back pain, work situations, and capacity of the pilot were analyzed. RESULTS: The self-reported 1 yr prevalence of regular or continuous neck and lower back pain in 2014 were 22% and 31%, respectively, compared to both being 12% in 2007. Age, military flying experience, total number of flying hours, flying hours on the F-16, and total number of hours flown with night vision goggles (NVG) were significantly higher in 2014. In 2014, 95% flew with JHMCS, compared to 0% in 2007. Flying with JHMCS (88%), NVG (88%), type of flight (63%), and sitting posture (50%) were the most reported causes of flight-related neck pain. Sitting posture (89%), duration of flight (56%), and seat (44%) were among the reported causes of back pain. DISCUSSION: The increasing trend of neck and lower back pain might be caused by multiple changes in both the work situation and capacity of the pilots since 2007. Future innovations will increase the load on the pilot's spine. To successfully address their spinal problems in the future, fighter pilots must be monitored continuously. PMID- 26564760 TI - Solar Eye Protection Practices of Civilian Aircrew. AB - INTRODUCTION: There is good evidence that long term exposure to ultraviolet (UV) radiation increases the risk of cataracts. The 'blue light hazard' is considered a risk factor for retinal changes similar to those seen in macular degeneration. Previous studies ascertaining the prevalence of radiation related ocular disease in pilot cohorts have not considered use of solar eye protection. The aim of this study was to explore pilot use of sunglasses and other solar eye protection habits and to gain insight into the difficulties encountered managing sunlight on the flight deck. Additionally, the prevalence of radiation related ocular pathology in the study group was calculated. METHODS: A web based questionnaire was developed and administered to a large population of current UK professional pilots. RESULTS: There were 2917 respondents who completed the questionnaire, demonstrating a wide range of sunglass use during flight. A number of barriers to sunglass use were identified, the most prevalent being the requirement for corrective lenses to be used. Pilots most commonly increase sunglass use due to ocular health concerns. A high level of dissatisfaction with standard aircraft sun protection systems was reported. Long haul airline pilots were the highest users of nonstandard sunlight blocking strategies. No correlation between reported pathology and flying experience was found. DISCUSSION: The use of sunglasses during flight is complex; however, a number of practical recommendations can be made to increase the success for those pilots who wish to use sunglasses more. Aircraft manufacturers should consider how greater control of cockpit sunlight levels can be achieved. PMID- 26564759 TI - Development and Validation of the Cognition Test Battery for Spaceflight. AB - BACKGROUND: Sustained high-level cognitive performance is of paramount importance for the success of space missions, which involve environmental, physiological, and psychological stressors that may affect brain functions. Despite subjective symptom reports of cognitive fluctuations in spaceflight, the nature of neurobehavioral functioning in space has not been clarified. METHODS: We developed a computerized cognitive test battery (Cognition) that has sensitivity to multiple cognitive domains and was specifically designed for the high performing astronaut population. Cognition consists of 15 unique forms of 10 neuropsychological tests that cover a range of cognitive domains, including emotion processing, spatial orientation, and risk decision making. Cognition is based on tests known to engage specific brain regions as evidenced by functional neuroimaging. Here we describe the first normative and acute total sleep deprivation data on the Cognition test battery as well as several efforts underway to establish the validity, sensitivity, feasibility, and acceptability of Cognition. RESULTS: Practice effects and test-retest variability differed substantially between the 10 Cognition tests, illustrating the importance of normative data that both reflect practice effects and differences in stimulus set difficulty in the population of interest. After one night without sleep, medium to large effect sizes were observed for 3 of the 10 tests addressing vigilant attention (Cohen's d = 1.00), cognitive throughput (d = 0.68), and abstract reasoning (d = 0.65). CONCLUSIONS: In addition to providing neuroimaging-based novel information on the effects of spaceflight on a range of cognitive functions, Cognition will facilitate comparing the effects of ground-based analogues to spaceflight, increase consistency across projects, and thus enable meta-analyses. PMID- 26564761 TI - Recurrent and Transient Spinal Pain Among Commercial Helicopter Pilots. AB - OBJECTIVE: The aim of this study was to provide information on the occurrence of spinal pain, i.e., low back and neck pain, among commercial helicopter pilots, along with possible associations between pain and anthropometric and demographic factors and flying exposure. METHODS: Data were collected through a subjective and retrospective survey among all the 313 (294 men, 19 women) full-time pilots employed by two helicopter companies. A questionnaire was used to assess the extent of spinal complaints in a transient and recurrent pain pattern along with information on physical activities, occupational flying experience, and airframes. RESULTS: The survey had 207 responders (194 men, 13 women). The pilots had extensive flying experience. Spinal pain was reported by 67%. Flying-related transient pain was reported among 50%, whereas recurrent spinal pain, not necessarily associated with flying, was reported by 52%. Women experienced more pain, but sample size prevented further conclusions. Male pilots reporting any spinal pain flew significantly more hours last year (median 500 h, IQR 400-650) versus men with no pain (median 445 h, IQR 300-550). Male pilots with transient or recurrent spinal pain did not differ from nonaffected male colleagues in the measured parameters. CONCLUSION: Spinal pain is a frequent problem among male and female commercial helicopter pilots. For men, no significant associations were revealed for transient or recurrent spinal pain with age, flying experience in years, total hours, annual flying time, type of aircraft, or anthropometric factors except for any spinal pain related to hours flown in the last year. PMID- 26564762 TI - Clinical Markers Associated with Metabolic Syndrome Among Military Aviators. AB - BACKGROUND: Due to the recent increase of metabolic syndrome (MetS) in the Korean population, this study was performed to investigate the prevalence of MetS among Republic of Korea (ROK) Air Force military aviators and its relationship with clinical markers. METHODS: A cross-sectional study was performed among 911 aviators who filled out the lifestyle questionnaire and underwent medical examinations at the ROK Air Force Aerospace Medical Center. Clinical markers of aviators with MetS were investigated and odds ratios were calculated. RESULTS: Among the 911 aviators, 90 (9.9%) were found to have MetS and the prevalence of subcomponents were: 31.7% elevated blood pressure, 25.3% elevated waist circumference, 19.0% impaired glucose tolerance, 16.6% elevated triglycerides, 7.9% reduced high density lipoprotein (HDL) cholesterol. Among aviators, a significant statistical association was found between the diagnosis of MetS with the highest quartile of uric acid, white blood cell (WBC) count, and alanine transaminase (ALT) level. Adjusted odds ratio of MetS was 8.88 (3.16 ~24.99) if all three clinical markers were at highest quartile range. DISCUSSION: Despite the relatively low prevalence of MetS in ROK Air Force aviators, further preventive measures are required as the prevalence is expected to increase in the future. Aviators with high levels of WBC count, uric acid, and ALT should be examined for MetS. Further comprehensive cohort study is required to link the elevation of clinical markers and development of MetS. PMID- 26564763 TI - Exercise Improves Mood State in Normobaric Hypoxia. AB - BACKGROUND: The purpose of this study was to quantify the efficacy of using exercise to alleviate the impairments in mood state associated with hypoxic exposure. METHODS: Nineteen young, healthy men completed Automated Neuropsychological Assessment Metrics-4(th) Edition (ANAM4) versions of the mood state test before hypoxia exposure, after 60 min of hypoxia exposure (12.5% O(2)), and during and after two intensities of cycling exercise (40% and 60% adjusted Vo(2max)) under the same hypoxic conditions. Peripheral oxygen saturation (Spo(2)) and regional cerebral oxygen saturation (rSo(2)) were continuously monitored. RESULTS: At rest in hypoxia, Total Mood Disturbance (TMD) was significantly increased compared to baseline in both the 40% and 60% groups. TMD was significantly decreased during exercise compared to rest in hypoxia. TMD was also significantly decreased during recovery compared to rest in hypoxia. Spo(2) significantly decreased at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. Regional cerebral oxygen saturation was also reduced at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. DISCUSSION: The current study demonstrated that exercise at 40% and 60% of adjusted Vo(2max) attenuated the adverse effects of hypoxia on mood. These findings may have significant applied value, as negative mood states are known to impair performance in hypoxia. Further studies are needed to replicate the current finding and to clarify the possible mechanisms associated with the potential benefits of exercise on mood state in normobaric hypoxia. PMID- 26564764 TI - Standardized Exercise Tests and Simulated Terrestrial Mission Task Performance. AB - BACKGROUND: Missions to terrestrial destinations (i.e., asteroids, the Moon, and Mars) will consist of physically challenging mission-critical tasks. These tasks, coupled with the negative physiological effects of prolonged microgravity exposure, create a plausible situation in which physical requirements may exceed an astronaut's physical capacity. Therefore, the objective of the current study was to evaluate the association of aerobic fitness and muscular strength parameters with performance during two field tests designed to simulate upper body mission-critical activities. METHODS: There were 70 subjects who completed a material transport field test requiring the loading, transport, and unloading of geological samples and a device operations field test consisting of tasks associated with equipment set-up and the operations of controls and valves. The relationships between test duration and the following measurements were determined: running Vo(2max), gas exchange threshold (GET), speed at Vo(2max) (s Vo(2max)), highest sustainable rate of aerobic metabolism [critical speed (CS)], and the finite distance that could be covered above CS (D'); and arm cranking Vo(2peak), GET, critical power (CP), and the finite work that can be performed above CP (W'). RESULTS: CP (r = -0.66), CS (r = -0.56), and arm cranking Vo(2peak) (r = -0.54) were most strongly correlated with the material transport field test and decision tree analysis revealed CP as the best predictor of performance. For the device operations field test, CP (r = -0.70), CS (r = 0.62), and arm cranking peak power output (r = -0.56) were significant predictors. DISCUSSION: Arm cranking tests are strongly associated with upper body dependent tasks, highlighting that the nature of mission tasks needs to be considered when evaluating astronaut physical capacity. PMID- 26564765 TI - Bias from Differential Exposure Measurement Error in a Study of Flight Attendants. AB - BACKGROUND: Self-reported occupational exposures are often used in epidemiological studies when actual exposure measurements are unavailable, which could cause measurement error and bias study results. This study provides a numeric example of this potential bias. METHODS: A study of block hours and preterm birth was used as an illustrative example. This study included 577 flight attendants, ages 18-45 yr, who gave birth to a term (37 or greater gestational weeks) or preterm (20-36 gestational weeks) infant between 1992 and 1996. Flight attendants self-reported the number of block hours flown during the first trimester of pregnancy; the number of block hours flown during the first trimester of pregnancy was also calculated from airline records. No adjustment for confounding was performed for this illustrative example. RESULTS: Although flight attendants having term and preterm births self-reported similar hours worked during the first trimester (median 213 vs. 215 block hours), airline records showed that flight attendants having term births worked more hours than those having preterm births (median 146 vs. 104 block hours). Using self-reported block hours, there was no association between block hours and preterm birth; when using airline records, an inverse association was observed. DISCUSSION: In this example, differential measurement error from use of self-reported block hours obscured an inverse association apparent when using airline records, demonstrating the importance of accurate exposure assessment for identifying occupational risk factors for health outcomes. PMID- 26564766 TI - An Unusual Complication of Barotrauma at Altitude. AB - BACKGROUND: A case of unilateral optic neuropathy secondary to barotrauma following a medial orbital wall fracture is presented. CASE REPORT: A 41-yr-old U.S. Air Force aviator presented for a routine periodic health assessment. Evaluation uncovered a suspected acquired color deficiency in the right eye (OD). Subsequent discussions with the patient revealed a history of eye pain, redness, and proptosis during a flight overseas several years earlier. Local ocular examination demonstrated asymmetric optic nerve cupping, optic nerve pallor OD, a mild asymmetric color deficit, and a significant visual field defect OD. Evaluation with magnetic resonance imaging revealed findings consistent with an old medial orbital wall fracture OD and optic nerve findings consistent with optic neuropathy. Follow-up evaluation by neurology and otorhinolaryngology demonstrated only extensive sinus pathology. Based upon these findings, it is postulated that the member suffered a medial orbital wall fracture at altitude during ascent caused by expanding ethmoid sinus gases due to abnormal sinus anatomy with subsequent right optic nerve injury leading to an optic neuropathy and subsequent visual sequelae. DISCUSSION: This case demonstrates one possible complication of active sinus disease while working in the aerospace environment. Several case reports have been published demonstrating the potential link between eye injuries and working in an environment with fluctuating atmospheric pressure. However, literature addressing the specific in-flight environment causing such complications is lacking. Furthermore, the case supports the need for versatility and a broad knowledge base in practicing flight surgeons to evaluate ocular pathology. PMID- 26564767 TI - Centrifuge-Simulated Suborbital Spaceflight in a Subject with Cardiac Malformation. AB - INTRODUCTION: Commercial spaceflight participants (SFPs) will introduce new medical challenges to the aerospace community, with unique medical conditions never before exposed to the space environment. This is a case report regarding the response of a subject with multiple cardiac malformations, including aortic insufficiency, pulmonary atresia, pulmonary valve replacement, ventricular septal defect (post-repair), and pulmonary artery stenosis (post-dilation), to centrifuge acceleration simulating suborbital flight. CASE REPORT: A 23-yr-old man with a history of multiple congenital cardiac malformations underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z), run 2) and two +G(x) runs (peak = +6.0 G(x), run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z)). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Despite the subject's significant medical history, he tolerated the acceleration profiles well and demonstrated no significant abnormal physiological responses. DISCUSSION: Potential risks to SFPs with aortic insufficiency, artificial heart valves, or valvular insufficiency include lower +G(z) tolerance, earlier symptom onset, and ineffective mitigation strategies such as anti-G straining maneuvers. There are no prior studies of prolonged accelerations approximating spaceflight in such individuals. This case demonstrates tolerance of acceleration profiles in an otherwise young and healthy individual with significant cardiac malformations, suggesting that such conditions may not necessarily preclude participation in commercial spaceflight. PMID- 26564768 TI - You're the Flight Surgeon: Keratoconus. PMID- 26564769 TI - You're the Flight Surgeon: Meckel's diverticulum. PMID- 26564770 TI - The Bohannon Hypothesis. PMID- 26564772 TI - This Month in Aerospace Medicine History. PMID- 26564773 TI - Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats. AB - AIMS: Melatonin is supposed to be an effective hepatoprotective agent. The effects and mechanisms of melatonin on alcoholic fatty liver (AFL) have not been well explored. The aim of this study was to investigate the preventive and therapeutic effects of melatonin on alcohol-induced fatty liver rats. METHODS: The AFL rats were induced by intragastric infusion of alcohol plus a high-fat diet for 6 weeks, and melatonin (10, 20, 40 mg/kg) was administered by gastric perfusion. We also established fatty acid overload cell model in HepG2 cells to investigate the effect of melatonin on AMP-activated protein kinase (AMPK) activity. RESULTS: The results showed that melatonin (20 and 40 mg/kg) administration significantly reduced alcohol-induced hepatic steatosis with lowering activities of serum alanine aminotransferase, aspartate aminotransferase and levels of serum and hepatic triglyceride. The activity of superoxide dismutase was increased and the content of malondialdehyde was decreased in liver homogenates of rats treated with melatonin. Melatonin increased the phosphorylation of AMPK in the liver tissues of alcohol-induced rats as well. Additionally, in vitro studies showed that melatonin increased the expression of melatonin1A receptor (MT1R), whereas luzindole, a receptor antagonist of melatonin, had no effect on its expression. In addition, melatonin reduced the levels of adenosine 3',5'-cyclic monophosphate (cAMP) and increased the phosphorylation of AMPK, and melatonin treatment could markedly reverse these effects. CONCLUSION: In conclusion, melatonin could protect against liver injury caused by alcohol gastric perfusion. The effect may be related to alleviating lipid peroxidation and upregulating the activity of AMPK mediated by MT1R signaling pathway. PMID- 26564774 TI - Insertion Homo- and Copolymerization of Diallyl Ether. AB - The previously unresolved issue of polymerization of allyl monomers CH2 ?CHCH2 X is overcome by a palladium-catalyzed insertion polymerization of diallyl ether as a monomer. An enhanced 2,1-insertion of diallyl ether as compared to mono-allyl ether retards the formation of an unreactive five-membered cyclic O-chelate (after 1,2-insertion) that otherwise hinders further polymerization, and also enhances incorporation in ethylene polymers (20.4 mol %). Cyclic ether repeat units are formed selectively (96 %-99 %) by an intramolecular insertion of the second allyl moiety of the monomer. These features even enable a homopolymerization to yield polymers (poly-diallyl ether) with degrees of polymerization of DPn ~44. PMID- 26564776 TI - Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era. AB - Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review. PMID- 26564775 TI - Formin and capping protein together embrace the actin filament in a menage a trois. AB - Proteins targeting actin filament barbed ends play a pivotal role in motile processes. While formins enhance filament assembly, capping protein (CP) blocks polymerization. On their own, they both bind barbed ends with high affinity and very slow dissociation. Their barbed-end binding is thought to be mutually exclusive. CP has recently been shown to be present in filopodia and controls their morphology and dynamics. Here we explore how CP and formins may functionally coregulate filament barbed-end assembly. We show, using kinetic analysis of individual filaments by microfluidics-assisted fluorescence microscopy, that CP and mDia1 formin are able to simultaneously bind barbed ends. This is further confirmed using single-molecule imaging. Their mutually weakened binding enables rapid displacement of one by the other. We show that formin FMNL2 behaves similarly, thus suggesting that this is a general property of formins. Implications in filopodia regulation and barbed-end structural regulation are discussed. PMID- 26564778 TI - Pseudoangiomatous xanthelasmoid mastocytosis: two case reports showing the hypervascularity of this rare variant of cutaneous mastocytosis. AB - Xanthelasmoid mastocytosis or xanthelasmoidea is a rare clinical variant of cutaneous mastocytosis characterized by a yellow hue of the clinical lesions, which are often misdiagnosed as juvenile xanthogranuloma. We present two pediatric cases of xanthelasmoid mastocytosis presenting as isolated mastocytomas, which are notable histopathologically for their hypervascularity. This pseudoangiomatous variant of cutaneous mastocytosis is important for pathologists to have knowledge of, so that a diagnosis of a vascular tumor is not rendered accidentally. The yellow hue has previously been explained by the usual deep and solid dermal mast cell infiltrate. In the two presented cases, however, the mast cell infiltrate was sparse, and the yellow color cannot be related to infiltrate density. We believe that the hypervascularity is at least one factor in the production of clinical xanthelasmoid appearance, and we propose the term 'pseudoangiomatous xanthelasmoid mastocytosis' to properly describe this rare variant of cutaneous mastocytosis. PMID- 26564777 TI - Identification of neurotoxic cytokines by profiling Alzheimer's disease tissues and neuron culture viability screening. AB - Alzheimer's disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that the activity of amyloid beta (Abeta) represents only one aspect of AD pathogenesis. Since neuroinflammation is thought to play an important role in AD, we hypothesized that cytokines may play a direct role in promoting neuronal death. Here, we profiled cytokine expression in a small cohort of human AD and control brain tissues. We identified AD associated cytokines using partial least squares regression to correlate cytokine expression with quantified pathologic disease state and then used neuron cultures to test whether cytokines up-regulated in AD tissues could affect neuronal viability. This analysis identified cytokines that were associated with the pathological severity. Of the top correlates, only TNF-alpha reduced viability in neuron culture when applied alone. VEGF also reduced viability when applied together with Abeta, which was surprising because VEGF has been viewed as a neuro protective protein. We found that this synthetic pro-death effect of VEGF in the context of Abeta was commensurate with VEGFR-dependent changes in multiple signaling pathways that govern cell fate. Our findings suggest that profiling of tissues combined with a culture-based screening approach can successfully identify new mechanisms driving neuronal death. PMID- 26564779 TI - Zinc-Catalyzed Dehydrogenative Cross-Coupling of Terminal Alkynes with Aldehydes: Access to Ynones. AB - Because of the lack of redox ability, zinc has seldom been used as a catalyst in dehydrogenative cross-coupling reactions. Herein, a novel zinc-catalyzed dehydrogenative C(sp(2) )?H/C(sp)?H cross-coupling of terminal alkynes with aldehydes was developed, and provides a simple way to access ynones from readily available materials under mild reaction conditions. Good reaction selectivity can be achieved with a 1:1 ratio of terminal alkyne and aldehyde. Various terminal alkynes and aldehydes are suitable in this transformation. PMID- 26564780 TI - Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture. AB - Investigating the susceptibility of oestrogen receptor-positive (ER(pos)) normal human breast epithelial cells (HBECs) for clinical purposes or basic research awaits a proficient cell-based assay. Here we set out to identify markers for isolating ER(pos) cells and to expand what appear to be post-mitotic primary cells into exponentially growing cultures. We report a robust technique for isolating ER(pos) HBECs from reduction mammoplasties by FACS using two cell surface markers, CD166 and CD117, and an intracellular cytokeratin marker, Ks20.8, for further tracking single cells in culture. We show that ER(pos) HBECs are released from growth restraint by small molecule inhibitors of TGFbeta signalling, and that growth is augmented further in response to oestrogen. Importantly, ER signalling is functionally active in ER(pos) cells in extended culture. These findings open a new avenue of experimentation with normal ER(pos) HBECs and provide a basis for understanding the evolution of human breast cancer. PMID- 26564781 TI - Efficient Generation of Myostatin Mutations in Pigs Using the CRISPR/Cas9 System. AB - Genetically modified pigs are increasingly used for biomedical and agricultural applications. The efficient CRISPR/Cas9 gene editing system holds great promise for the generation of gene-targeting pigs without selection marker genes. In this study, we aimed to disrupt the porcine myostatin (MSTN) gene, which functions as a negative regulator of muscle growth. The transfection efficiency of porcine fetal fibroblasts (PFFs) was improved to facilitate the targeting of Cas9/gRNA. We also demonstrated that Cas9/gRNA can induce non-homologous end-joining (NHEJ), long fragment deletions/inversions and homology-directed repair (HDR) at the MSTN locus of PFFs. Single-cell MSTN knockout colonies were used to generate cloned pigs via somatic cell nuclear transfer (SCNT), which resulted in 8 marker-gene free cloned pigs with biallelic mutations. Some of the piglets showed obvious intermuscular grooves and enlarged tongues, which are characteristic of the double muscling (DM) phenotype. The protein level of MSTN was decreased in the mutant cloned pigs compared with the wild-type controls, and the mRNA levels of MSTN and related signaling pathway factors were also analyzed. Finally, we carefully assessed off-target mutations in the cloned pigs. The gene editing platform used in this study can efficiently generate genetically modified pigs with biological safety. PMID- 26564782 TI - 'I felt a little bubbly in my tummy': eliciting pre-schoolers' accounts of their health visit using a computer-assisted interview method. AB - BACKGROUND: In the health care services, children's rights to participate in all matters that concern them are considered important. However, in practice this can be challenging with young children. In My Shoes (IMS) is a computer-assisted interview tool developed to help children talk about their experiences. The aim of the study was to evaluate the IMS' ability to elicit pre-schoolers' subjective experiences and accurate accounts of a routine health visit as well as the children's engagement in the interview process. METHODS: Interviews were conducted with 23 children aged 4-5 years, 2-4 weeks after their health visit. The interviews were transcribed verbatim and analysed using a method inspired by Content Analysis to evaluate IMS's ability to elicit accounts about subjective experiences. Accurate accounts were assessed by comparing the transcribed interviews with the filmed visits at the child health centre. The children's engagement was defined by the completion and length of the interviews, and the children's interaction with the software. RESULTS: All children gave accounts about their subjective experiences, such as their emotional state during the visit, available toys or rewards they received. All children related to the correct event, they all named at least one person who was present and 87% correctly named at least one examination procedure. The majority of children (91%) completed the interview, which lasted 17-39 min (M = 24), and 96% interacted with the IMS software. CONCLUSIONS: IMS was feasible to help children describe their health care experiences, in both detail and depth. The children interacted with the software and maintained their interest for an extended period of time. PMID- 26564783 TI - Reversibility and criticality in amorphous solids. AB - The physical processes governing the onset of yield, where a material changes its shape permanently under external deformation, are not yet understood for amorphous solids that are intrinsically disordered. Here, using molecular dynamics simulations and mean-field theory, we show that at a critical strain amplitude the sizes of clusters of atoms undergoing cooperative rearrangements of displacements (avalanches) diverges. We compare this non-equilibrium critical behaviour to the prevailing concept of a 'front depinning' transition that has been used to describe steady-state avalanche behaviour in different materials. We explain why a depinning-like process can result in a transition from periodic to chaotic behaviour and why chaotic motion is not possible in pinned systems. These findings suggest that, at least for highly jammed amorphous systems, the irreversibility transition may be a side effect of depinning that occurs in systems where the disorder is not quenched. PMID- 26564784 TI - Synthesis of 1,1-Diborylalkenes through a Bronsted Base Catalyzed Reaction between Terminal Alkynes and Bis(pinacolato)diboron. AB - A method for the synthesis of 1,1-diborylalkenes through a Bronsted base catalyzed reaction between terminal alkynes and bis(pinacolato)diboron has been developed. The procedure allows direct synthesis of functionalized 1,1 diborylalkenes from various terminal alkynes including propiolates, propiolamides, and 2-ethynylazoles. PMID- 26564785 TI - X-ray phase-contrast tomography for high-spatial-resolution zebrafish muscle imaging. AB - Imaging of muscular structure with cellular or subcellular detail in whole-body animal models is of key importance for understanding muscular disease and assessing interventions. Classical histological methods for high-resolution imaging methods require excision, fixation and staining. Here we show that the three-dimensional muscular structure of unstained whole zebrafish can be imaged with sub-5 MUm detail with X-ray phase-contrast tomography. Our method relies on a laboratory propagation-based phase-contrast system tailored for detection of low-contrast 4-6 MUm subcellular myofibrils. The method is demonstrated on 20 days post fertilization zebrafish larvae and comparative histology confirms that we resolve individual myofibrils in the whole-body animal. X-ray imaging of healthy zebrafish show the expected structured muscle pattern while specimen with a dystrophin deficiency (sapje) displays an unstructured pattern, typical of Duchenne muscular dystrophy. The method opens up for whole-body imaging with sub cellular detail also of other types of soft tissue and in different animal models. PMID- 26564786 TI - Praise matters: the influence of nurse unit managers' praise on nurses' practice, work environment and job satisfaction: a questionnaire study. AB - AIM: The aim of this study was to investigate the associations between praise from nurse unit managers and job satisfaction, professional practice, workload, work climate and organizational commitment of nurses caring for surgical patients. BACKGROUND: Praise influences experiences of employees. DESIGN: Web based, cross-sectional explorative survey design. METHODS: A structured questionnaire was used to measure praise given by nurse unit managers as perceived by nurses (n = 383; 49% response rate) working with surgical patients. Data were collected between December 2009-January 2010. Several variables assessed the major concepts under study. Binary logistic regression analysis was employed to compare nurses who receive praise very rarely/rarely as compared with very often/rather often. RESULTS: Praise was received often/very often by 31.6% of participants. Compared with nurses receiving praise rarely/very rarely those who received it often/rather showed more job satisfaction, stated they had more opportunities to practice professionally, described a more positive work climate and were more committed to the organization such as being proud to work at and willing to make effort for the unit and hospital. There was no difference between the groups regarding workload. Main findings of the regression analysis were that nurses display their organizational commitment by not thinking about leaving the current workplace and those who value professional recognition are likelier to receive praise than their counterparts. CONCLUSION: Nurse unit managers should praise their staff in a realistic fashion. Such praise is cost-effective, takes short time, produces positive influences on members of their staff and may improve patient safety. PMID- 26564788 TI - Corrosion-Mediated Self-Assembly (CMSA): Direct Writing Towards Sculpturing of 3D Tunable Functional Nanostructures. AB - Inexpensive and readily available metal foils have been extracted and sculptured into nanocomposites without the expense of applied energy. The unwanted corrosion phenomenon has been contrarily utilized to realize desirable 3D nanostructures through a corrosion-mediated self-assembly (CMSA) method, which is unattainable by conventional 2D patterning routes. By virtue of electrochemical dissolution/re deposition initiated by brass corrosion, ionic derivatives (Zn(2+) and Cu(2+) ) are continuously supplied and seized by etchant ions (PO4 (3-) ) to self-assemble into well-defined nanocomposites. Beyond 3D geometry patterning, CMSA enables arbitrarily tailoring of structures and chemical compositions with in situ multiphase amalgamation of hybrid materials, which improves homogeneity and thus mitigates phase separation issues. Importantly, the CMSA technique is demonstrated on transition metals for functional photocatalytic applications. PMID- 26564787 TI - Structure and dynamics of polymyxin-resistance-associated response regulator PmrA in complex with promoter DNA. AB - PmrA, an OmpR/PhoB family response regulator, manages genes for antibiotic resistance. Phosphorylation of OmpR/PhoB response regulator induces the formation of a symmetric dimer in the N-terminal receiver domain (REC), promoting two C terminal DNA-binding domains (DBDs) to recognize promoter DNA to elicit adaptive responses. Recently, determination of the KdpE-DNA complex structure revealed an REC-DBD interface in the upstream protomer that may be necessary for transcription activation. Here, we report the 3.2-A-resolution crystal structure of the PmrA-DNA complex, which reveals a similar yet different REC-DBD interface. However, NMR studies show that in the DNA-bound state, two domains tumble separately and an REC-DBD interaction is transiently populated in solution. Reporter gene analyses of PmrA variants with altered interface residues suggest that the interface is not crucial for supporting gene expression. We propose that REC-DBD interdomain dynamics and the DBD-DBD interface help PmrA interact with RNA polymerase holoenzyme to activate downstream gene transcription. PMID- 26564790 TI - The Coracohumeral Distance in Shoulders With Traumatic and Degenerative Subscapularis Tendon Tears. AB - BACKGROUND: A reduced coracohumeral distance (CHD) is thought to be responsible for subcoracoid impingement. This only accounts for degenerative tendon tears. In traumatic tears, the subcoracoid space should be normal. HYPOTHESIS: The CHD in patients with traumatic subscapularis tendon tears is larger than that in patients with degenerative tears and does not differ from patients with an intact subscapularis tendon. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 83 patients with arthroscopically certified subscapularis tendon tears were included in the study. Forty-four patients had degenerative causes (group 1), and 39 had traumatic causes (group 2). The control group consisted of 20 patients with traumatic supraspinatus tendon tears and arthroscopically proven, intact subscapularis tendons (group 3). On preoperative axial magnetic resonance imaging, the distance between the CHD was measured, and the values of the 3 groups were compared using the t test. RESULTS: The mean (+/-SD) CHD in patients with degenerative subscapularis tendon tears was 8.6 +/- 2.0 mm (range, 4.0-13.2 mm) and was significantly (P = .0003) smaller than that in patients with traumatic tears (10.2 +/- 2.0 mm; range, 6.6-16.2 mm) or controls (10.4 +/- 1.8 mm; range, 6.8-14.0 mm). The CHD of controls and patients with traumatic tears did not differ significantly (P = .7875). A CHD of less than 6 mm only occurred in patients with degenerative subscapularis tendon tears. CONCLUSION: The hypothesis that the CHD in patients with degenerative subscapularis tendon tears is significantly smaller than that in patients with traumatic tears or intact subscapularis tendons was confirmed. The CHD in patients with traumatic tears does not differ from that in controls. A CHD of less than 6 mm only occurs in patients with degenerative subscapularis tendon tears. PMID- 26564789 TI - TAK1 Regulates Myocardial Response to Pathological Stress via NFAT, NFkappaB, and Bnip3 Pathways. AB - TAK1 (TGFbeta-activated kinase-1) signaling is essential in regulating a number of important biological functions, including innate immunity, inflammatory response, cell growth and differentiation, and myocardial homeostasis. The precise role of TAK1 in the adult heart under pathological conditions remains largely unknown. Importantly, we observed that TAK1 is upregulated during compensatory hypertrophy but downregulated in end-stage heart failure. Here we generated transgenic mice with inducible expression of an active TAK1 mutant (TAK1DeltaN) in the adult heart. TAK1DeltaN transgenic mice developed greater cardiac hypertrophy compared with control mice after transverse aortic constriction (TAC), which was largely blocked by ablation of calcineurin Abeta. Expression of TAK1DeltaN also promoted NFAT (nuclear factor of activated T-cells) transcriptional activity in luciferase reporter mice at baseline, which was further enhanced after TAC. Our results revealed that activation of TAK1 promoted adaptive cardiac hypertrophy through a cross-talk between calcineurin-NFAT and IKK-NFkappaB pathways. More significantly, adult-onset inducible expression of TAK1DeltaN protected the myocardium from adverse remodeling and heart failure after myocardial infarction or long-term pressure overload, by preventing cardiac cell death and fibrosis. Mechanistically, TAK1 exerts its cardioprotective effect through activation of NFAT/NFkappaB, downregulation of Bnip3, and inhibition of cardiac cell death. PMID- 26564791 TI - Combined Subscapularis Tears in Massive Posterosuperior Rotator Cuff Tears: Do They Affect Postoperative Shoulder Function and Rotator Cuff Integrity? AB - BACKGROUND: Previous studies on massive rotator cuff tears have not addressed the outcomes of tears extending to the subscapularis tendon. HYPOTHESIS: The retear rate in patients with a massive posterosuperior rotator cuff tear combined with a subscapularis tear is higher than that in patients with a massive posterosuperior rotator cuff tear with an intact subscapularis tendon. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data were collected and analyzed from 92 consecutive patients who underwent arthroscopic repair of a massive posterosuperior rotator cuff tear. Patients were divided into 3 groups according to the status of the subscapularis tendon: intact subscapularis tendon (I-massive tear; n = 42), tear involving half or less than half of the subscapularis tendon (S-massive tear; n = 22), and tear involving more than half of the subscapularis tendon (L-massive tear; n = 28). The integrity of the rotator cuff was determined by ultrasonography at 4.5 and 12 months or later after surgery. Clinical evaluations were performed using the visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, the Constant score, and active shoulder range of motion. Data were collected on the day before surgery and at final follow-up (at least 24 months postoperatively). RESULTS: A total of 25 retears (27%) were identified based on an ultrasonographic evaluation. Although statistical significance was not found, there was a trend toward a higher retear rate in patients with an L-massive tear (43%) compared with those with an S massive tear (18%; P = .050) or I-massive tear (21%; P = .059) at final follow up. The subclassification of retears according to the involved tendons revealed that subsequent retears of the subscapularis tendon were noted only in patients with an L-massive tear. In patients with an L-massive tear, postoperative data comparison between patients with intact subscapularis tendons and those with failed subscapularis tendons revealed that a significant difference was noted in the VAS (1.1 vs 3.8, respectively) and ASES (90.6 vs 58.5, respectively) scores. The improvement in clinical scores after repair was statistically significant in all groups but not different between the groups. CONCLUSION: The arthroscopic repair of massive tears results in substantial improvements in shoulder function, regardless of the presence of combined subscapularis tears. However, this study showed a trend toward a high failure rate for the repair of massive posterosuperior rotator cuff tears extending over half of the subscapularis tendon. Therefore, other treatment options should also be considered for this type of rotator cuff tear. PMID- 26564792 TI - Quantitative In Situ Analysis of the Anterior Cruciate Ligament: Length, Midsubstance Cross-sectional Area, and Insertion Site Areas. AB - BACKGROUND: Quantification of the cross-sectional area (CSA) of the anterior cruciate ligament (ACL) in different loading conditions is important for understanding the native anatomy and thus achieving anatomic reconstruction. The ACL insertion sites are larger than the ACL midsubstance, and the isthmus (region of the smallest CSA) location may vary with the load or flexion angle. PURPOSE: To (1) quantify the CSA along the entire ACL, (2) describe the location of the ACL isthmus, (3) explore the relationship between ACL length and CSA, and (4) validate magnetic resonance imaging (MRI) for assessing the CSA of the midsubstance ACL. STUDY DESIGN: Descriptive laboratory study. METHODS: Eight cadaveric knees were dissected to expose the ACL and its attachments. Knees were positioned using a robotic loading system through a range of flexion angles in 3 loading states: (1) unloaded, (2) anterior tibial translation, and (3) combined rotational load of valgus and internal torque. Laser scanning quantified the shape of the ACL and its insertion site boundaries. The CSA of the ACL was measured, and the location of the isthmus was determined; the CSA of the ACL was also estimated from MRI and compared with the laser-scanned data. RESULTS: The CSA of the ACL varied along the ligament, and the isthmus existed at an average (+/-SD) of 53.8% +/- 5.5% of the distance from the tibial insertion center to the femoral insertion center. The average CSA at the isthmus was smallest in extension (39.9 +/- 13.7 mm(2)) and increased with flexion (43.9 +/- 12.1 mm(2) at 90 degrees ). The ACL length was shortest at 90 degrees of flexion and increased by 18.8% +/- 10.1% in unloaded extension. Application of an anterior load increased the ACL length by 5.0% +/- 3.3% in extension, and application of a combined rotational load increased its length by 4.1% +/- 3.0% in extension. CONCLUSION: The ACL isthmus is located almost half of the distance between the insertion sites. The CSA of the ACL at the isthmus is largest with the knee unloaded and at 90 degrees of flexion, and the area decreases with extension and applied loads. The CSA at the isthmus represents less than half the area of the insertion sites. CLINICAL RELEVANCE: These results may aid surgical planning, specifically for choosing a graft size and fixation angle that most closely matches the native anatomy and function across the entire range of knee motion. PMID- 26564793 TI - Understanding sustained domestic violence identification in maternal and child health nurse care: process evaluation from a 2-year follow-up of the MOVE trial. AB - AIM: To investigate factors contributing to the sustained domestic violence screening and support practices of Maternal and Child Health nurses 2 years after a randomized controlled trial. BACKGROUND: Domestic violence screening by healthcare professionals has been implemented in many primary care settings. Barriers to screening exist and screening rates remain low. Evidence for longer term integration of nurse screening is minimal. Trial outcomes showed sustained safety planning behaviours by intervention group nurses. DESIGN: Process evaluation in 2-year follow-up of a cluster randomized controlled trial. METHODS: Evaluation included a repeat online nurse survey and 14 interviews (July September 2013). Survey analysis included comparison of proportionate group difference between arms and between trial baseline and 2 year follow-up surveys. Framework analysis was used to assess qualitative data. Normalization Process Theory informed evaluation design and interpretation of results. RESULTS: Survey response was 77% (n = 123/160). Sustainability of nurse identification of domestic violence appeared to be due to greater nurse discussion and domestic violence disclosure by women, facilitated by use of a maternal health and well being checklist. Over time, intervention group nurses used the maternal checklist more at specific maternal health visits and found the checklist the most helpful resource assisting their domestic violence work. Nurses' spoke of a degree of 'normalization' to domestic violence screening that will need constant investment to maintain. CONCLUSION: Sustainable domestic violence screening and support outcomes can be achieved in an environment of comprehensive, nurse designed and theory driven implementation. Continuing training, discussion and monitoring of domestic violence work is needed to retain sustainable practices. PMID- 26564794 TI - Sequential posttranslational modifications regulate PKC degradation. AB - Cross-talk among different types of posttranslational modifications (PTMs) has emerged as an important regulatory mechanism for protein function. Here we elucidate a mechanism that controls PKCalpha stability via a sequential cascade of PTMs. We demonstrate that PKCalpha dephosphorylation decreases its sumoylation, which in turn promotes its ubiquitination and ultimately enhances its degradation via the ubiquitin-proteasome pathway. These findings provide a molecular explanation for the activation-induced down-regulation of PKC proteins. PMID- 26564795 TI - Epigenetic engineering shows that a human centromere resists silencing mediated by H3K27me3/K9me3. AB - Centromeres are characterized by the centromere-specific H3 variant CENP-A, which is embedded in chromatin with a pattern characteristic of active transcription that is required for centromere identity. It is unclear how centromeres remain transcriptionally active despite being flanked by repressive pericentric heterochromatin. To further understand centrochromatin's response to repressive signals, we nucleated a Polycomb-like chromatin state within the centromere of a human artificial chromosome (HAC) by tethering the methyltransferase EZH2. This led to deposition of the H3K27me3 mark and PRC1 repressor binding. Surprisingly, this state did not abolish HAC centromere function or transcription, and this apparent resistance was not observed on a noncentromeric locus, where transcription was silenced. Directly tethering the reader/repressor PRC1 bypassed this resistance, inactivating the centromere. We observed analogous responses when tethering the heterochromatin Editor Suv39h1-methyltransferase domain (centromere resistance) or reader HP1alpha (centromere inactivation), respectively. Our results reveal that the HAC centromere can resist repressive pathways driven by H3K9me3/H3K27me3 and may help to explain how centromeres are able to resist inactivation by flanking heterochromatin. PMID- 26564796 TI - Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein. AB - Ubiquitin- and proteasome-dependent outer mitochondrial membrane (OMM)-associated degradation (OMMAD) is critical for mitochondrial and cellular homeostasis. However, the scope and molecular mechanisms of the OMMAD pathways are still not well understood. We report that the OMM-associated E3 ubiquitin ligase MARCH5 controls dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis. MARCH5 knockout selectively inhibited ubiquitination and proteasomal degradation of MiD49, a mitochondrial receptor of Drp1, and consequently led to mitochondrial fragmentation. Mitochondrial fragmentation in MARCH5(-/-) cells was not associated with inhibition of mitochondrial fusion or bioenergetic defects, supporting the possibility that MARCH5 is a negative regulator of mitochondrial fission. Both MARCH5 re-expression and MiD49 knockout in MARCH5(-/-) cells reversed mitochondrial fragmentation and reduced sensitivity to stress-induced apoptosis. These findings and data showing MARCH5-dependent degradation of MiD49 upon stress support the possibility that MARCH5 regulation of MiD49 is a novel mechanism controlling mitochondrial fission and, consequently, the cellular response to stress. PMID- 26564797 TI - GAR22beta regulates cell migration, sperm motility, and axoneme structure. AB - Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22beta), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22beta(-/-) Sertoli cells moved faster than wild-type cells. In addition, GAR22beta(-/-) cells showed a more prominent focal adhesion turnover. GAR22beta overexpression or its reexpression in GAR22beta(-/-) cells reduced cell motility and focal adhesion turnover. GAR22beta-actin interaction was stronger than GAR22beta-microtubule interaction, resulting in GAR22beta localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22beta interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22beta-EB1 interaction was required for the ability of GAR22beta to modulate cell motility. We found that GAR22beta is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22beta as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes. PMID- 26564798 TI - Actin- and microtubule-dependent regulation of Golgi morphology by FHDC1. AB - The Golgi apparatus is the central hub of intracellular trafficking and consists of tethered stacks of cis, medial, and trans cisternae. In mammalian cells, these cisternae are stitched together as a perinuclear Golgi ribbon, which is required for the establishment of cell polarity and normal subcellular organization. We previously identified FHDC1 (also known as INF1) as a unique microtubule-binding member of the formin family of cytoskeletal-remodeling proteins. We show here that endogenous FHDC1 regulates Golgi ribbon formation and has an apparent preferential association with the Golgi-derived microtubule network. Knockdown of FHDC1 expression results in defective Golgi assembly and suggests a role for FHDC1 in maintenance of the Golgi-derived microtubule network. Similarly, overexpression of FHDC1 induces dispersion of the Golgi ribbon into functional ministacks. This effect is independent of centrosome-derived microtubules and instead likely requires the interaction between the FHDC1 microtubule-binding domain and the Golgi-derived microtubule network. These effects also depend on the interaction between the FHDC1 FH2 domain and the actin cytoskeleton. Thus our results suggest that the coordination of actin and microtubule dynamics by FHDC1 is required for normal Golgi ribbon formation. PMID- 26564799 TI - Chromatin binding of RCC1 during mitosis is important for its nuclear localization in interphase. AB - RCC1, a guanine nucleotide exchange factor of the small GTPase Ran, plays various roles throughout the cell cycle. However, the functions of RCC1 in biological processes in vivo are still unclear. In particular, although RCC1 has multifunctional domains, the biological significance of each domain is unclear. To examine each domain of RCC1, we established an RCC1 conditional knockout chicken DT40 cell line and introduced various RCC1 mutants into the knockout cells. We found that nuclear reformation did not occur properly in RCC1-deficient cells and examined whether specific RCC1 mutants could rescue this phenotype. Surprisingly, we found that neither the nuclear localization signal nor the chromatin-binding domain of RCC1 is essential for its function. However, codisruption of these domains resulted in defective nuclear reformation, which was rescued by artificial nuclear localization of RCC1. Our data indicate that chromatin association of RCC1 during mitosis is crucial for its proper nuclear localization in the next interphase. Moreover, proper nuclear localization of RCC1 in interphase is essential for its function through its nucleotide exchange activity. PMID- 26564801 TI - Combined effects of recent Pacific cooling and Indian Ocean warming on the Asian monsoon. AB - Recent research indicates that the cooling trend in the tropical Pacific Ocean over the past 15 years underlies the contemporaneous hiatus in global mean temperature increase. During the hiatus, the tropical Pacific Ocean displays a La Nina-like cooling pattern while sea surface temperature (SST) in the Indian Ocean has continued to increase. This SST pattern differs from the well-known La Nina induced basin-wide cooling across the Indian Ocean on the interannual timescale. Here, based on model experiments, we show that the SST pattern during the hiatus explains pronounced regional anomalies of rainfall in the Asian monsoon region and thermodynamic effects due to specific humidity change are secondary. Specifically, Indo-Pacific SST anomalies cause convection to intensify over the tropical western Pacific, which in turn suppresses rainfall in mid-latitude East Asia through atmospheric teleconnection. Overall, the tropical Pacific SST effect opposes and is greater than the Indian Ocean SST effect. PMID- 26564800 TI - Locus-specific gene repositioning in prostate cancer. AB - Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease. PMID- 26564802 TI - Carbon-Encapsulated Co3O4 Nanoparticles as Anode Materials with Super Lithium Storage Performance. AB - A high-performance anode material for lithium storage was successfully synthesized by glucose as carbon source and cobalt nitrate as Co3O4 precursor with the assistance of sodium chloride surface as a template to reduce the carbon sheet thickness. Ultrafine Co3O4 nanoparticles were homogeneously embedded in ultrathin porous graphitic carbon in this material. The carbon sheets, which have large specific surface area, high electronic conductivity, and outstanding mechanical flexibility, are very effective to keep the stability of Co3O4 nanoparticles which has a large capacity. As a consequence, a very high reversible capacity of up to 1413 mA h g(-1) at a current density of 0.1 A g(-1) after 100 cycles, a high rate capability (845, 560, 461 and 345 mA h g(-1) at 5, 10, 15 and 20 C, respectively, 1 C = 1 A g(-1)), and a superior cycling performance at an ultrahigh rate (760 mA h g(-1) at 5 C after 1000 cycles) are achieved by this lithium-ion-battery anode material. PMID- 26564803 TI - Toll-like receptor 5 is not essential for the promotion of secretory immunoglobulin A antibody responses to flagellated bacteria. AB - Toll-like receptor 5 recognizes bacterial flagellin, plays a critical role in innate immunity, and contributes to flagellin-specific humoral immunity. Further, TLR5-expressing dendritic cells play an important role in IgA synthesis in the intestine; however, the contribution of TLR5 to antigen (Ag)-specific mucosal immunity remains unclear. Thus, whether TLR5 is essential for the induction of intestinal secretory (S)IgA antibody (Ab) responses against flagellin and bacterial Ags attached to the bacterial surface in response to an oral flagellated bacterium, Salmonella, was explored in this study. Our results indicate that when TLR5 knockout (TLR5(-/-)) mice are orally immunized with recombinant Salmonella expressing fragment C of tetanus toxin (rSalmonella-Tox C), tetanus toxoid (TT)- and flagellin (FliC)-specific systemic IgG and intestinal SIgA Abs are elicited. The numbers of TT-specific IgG Ab-forming cells (AFCs) in the spleen and IgA AFCs in the lamina propria (LP) of TLR5(-/-) mice were comparable to those in wild-type mice. rSalmonella-Tox C was equally disseminated in TLR5(-/-) mice, TLR5(-/-) mice lacking Peyer's patches (PPs), and wild-type mice. In contrast, TLR5(-/-) PP-null mice failed to induce TT- and FliC specific SIgA Abs in the intestine and showed significantly reduced numbers of TT specific IgA AFCs in the LP. These results suggest that TLR5 is dispensable for the induction of flagellin and surface Ag-specific systemic and mucosal immunity against oral flagellated bacteria. Rather, pathogen recognition, which occurs in PPs, is a prerequisite for the induction of mucosal immunity against flagellated bacteria. PMID- 26564804 TI - Mannan-binding lectin at supraphysiological concentrations inhibits differentiation of dendritic cells from human CD14+ monocytes. AB - Mannan-binding lectin (MBL), a circulating C-type lectin, is an important member of the defense collagen family. It exhibits a high potential for recognizing broad categories of pathogen-associated molecular patterns and initiating complement cascade responses. DCs are well-known specialist antigen-presenting cells that significantly trigger specific T cell-mediated immune responses. In our previous study, it was observed that high concentrations of MBL significantly attenuate LPS-induced maturation of monocyte-derived DCs (MoDCs). In the current study, it was postulated that MBL at similar supraphysiological concentrations would affect early differentiation of MoDCs in some way. CD14(+) monocytes from human peripheral blood mononuclear cells were cultured with granulocyte macrophage colony-stimulating factor and IL-4 in the presence or absence of physiological (1 ug/mL) and supraphysiological concentrations (20 ug/mL) of MBL protein, respectively. Phenotypic analysis indicated that the differentiated DCs incubated with high concentrations of MBL expressed MHC class II and costimulatory molecules (e.g., CD80 and CD40) more weakly than did control groups. The secretion of IL-10 and IL-6 increased markedly, whereas their mixed lymphocyte reaction-stimulating capacity decreased. Members of the signal transducer and activator of transcription family were also found to be differentially regulated. Thus, beyond the role of MBL as an opsonin, our data reveal a possible inhibitory effect of MBL at high concentrations in monocyte-DC transition, which probably provides one way of regulating adaptive immune responses by strict regulation of DCs, making MBL a better prospect for controlling relevant pathological events such as autoimmune diseases. PMID- 26564805 TI - Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy. AB - The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein Barr virus (EBV) DNA > 4000 copies/mL, serum albumin <= 46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID- 26564806 TI - Hemodynamic response to ketamine in children with pulmonary hypertension. AB - BACKGROUND: The safety of ketamine in children with pulmonary hypertension has been debated because of conflicting results of prior studies in which changes in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) have been widely variable. The goal of this prospective study was to quantitate the effects of ketamine on pulmonary hemodynamics in a cohort of children with pulmonary hypertension under conditions in which variables such as airway/ventilatory management, FiO(2), and use of vasodilating anesthetics were controlled. METHODS: The IRB approved this study of 34 children undergoing cardiac catheterization for pulmonary hypertension studies. Following anesthetic induction with sevoflurane and tracheal intubation facilitated by the administration of rocuronium 0.7-1 mg.kg(-1) iv, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg.kg(-1) iv (or 0.5 mg.kg(-1) po preoperatively) and remifentanil iv infusion 0.5-0.7 mcg.kg(-1) .min(-1). Ventilation was mechanically controlled to maintain PaCO(2) 35-40 mmHg. When endtidal sevoflurane was 0% and FiO(2) was 0.21, baseline heart rate (HR), mean arterial pressure (MAP), mPAP, right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic pressure (RVEDP), cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance (SVRI), indexed pulmonary vascular resistance (PVRI), and cardiac index (CI) were calculated. Each child then received a bolus of ketamine 2 mg.kg(-1) infused over 2 min. Measurements and calculations were repeated 2 min after the conclusion of the infusion. RESULTS: The mean (95% CI) increase in mPAP following ketamine was 2 mmHg (0.2, 3.7), which was statistically significant but clinically insignificant. PVRI and PVRI/SVRI did not change significantly. Hemodynamic changes did not differ among subjects with differing severity of pulmonary hypertension or between subjects chronically treated with pulmonary vasodilators or not. CONCLUSION: Ketamine is associated with minimal, clinically insignificant hemodynamic changes in sedated, mechanically ventilated children with pulmonary hypertension. PMID- 26564807 TI - Effectiveness of medical taping concept in primary dysmenorrhoea: a two-armed randomized trial. AB - In 2014, we assessed the effectiveness of Medical Taping Concept (MTC) in Primary Dysmenorrhoea (PD) with a single-blind, two-armed clinical trial (NCT02114723, ClinicalTrials.gov) with a follow-up of 4 menstrual cycles (pre-intervention: 2 months; post-intervention: 2 months) in a sample formed by 129 Spanish women aged 18-30 years with PD. We had two groups: intervention group (75), MTC covering T 11 and T-12 dermatomes; control group (54), another taping in both greater trochanter areas. Our main outcome measures were: pre-intervention and post intervention increase in pain difference measured 2 hours after commencement (2-h pain - 0-h pain); difference between the number of tablets ingested post intervention and pre-intervention; and associated symptoms in post-intervention (fatigue, vomiting, diarrhoea, nausea and others). Pain was assessed in: abdomen, legs, head and lower back. We found significant differences (p < 0.05) for number of tablets, abdominal and leg pain. In conclusion, the intervention group had less abdominal and leg pain when pharmacological therapy was not started. Furthermore, the intervention resulted in a lower intake of tablets. Nevertheless, more studies are needed to corroborate our results and to analyze the MTC effectiveness if women do not take any tablets during the entire menstrual period. PMID- 26564808 TI - Bartonella henselae infection caused by cat flea bite. PMID- 26564809 TI - Topology of a G-quadruplex DNA formed by C9orf72 hexanucleotide repeats associated with ALS and FTD. AB - Abnormal expansions of an intronic hexanucleotide GGGGCC (G4C2) repeat of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. These structural polymorphisms lead to abortive transcripts and contribute to the pathogenesis of ALS and FTD. Using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, we analyzed the structures of C9orf72 HRE DNA with various G4C2 repeats. They exhibited diverse G-quadruplex folds in potassium ions. Furthermore, we determined the topology of a G-quadruplex formed by d(G4C2)4. It favors a monomeric fold and forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. Our findings highlight the conformational heterogeneity of C9orf72 HRE DNA, and may lay the necessary structural basis for designing small molecules for the modulation of ALS/FTD pathogenesis. PMID- 26564810 TI - Idiopathic non-specific interstitial pneumonia. AB - Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that may be idiopathic or secondary to connective tissue disease, toxins or numerous other causes. Idiopathic NSIP is a rare diagnosis and requires exclusion of these other possible causes. Patients typically present in mid-adulthood with dyspnoea, cough and often constitutional symptoms including fever and fatigue. The disease has a female predominance, and more than 50% of patients have never smoked. Physical exam features mild hypoxaemia and inspiratory rales. Pulmonary function tests demonstrate restriction and a low diffusing capacity for carbon monoxide. High-resolution computed tomography abnormalities include predominantly lower lobe subpleural reticular changes, traction bronchiectasis and ground-glass opacities; honeycombing is rarely seen. An evaluation of the underlying pathology is necessary for a firm diagnosis. Histologically, alveolar and interstitial mononuclear cell inflammation and fibrosis are seen in a temporally uniform pattern with preserved underlying alveolar architecture. NSIP must be differentiated from other parenchymal lung diseases including idiopathic pulmonary fibrosis and hypersensitivity pneumonitis. A thorough exposure history and assessment for underlying connective tissue diseases are highly important, as positive findings in these categories would likely denote a case of secondary NSIP. A multi-disciplinary discussion that includes pulmonologist(s), radiologist(s) and pathologist(s) assists in reaching a consensus diagnosis and improves diagnostic accuracy. Treatment of idiopathic NSIP, although not well proven, is generally instituted in the form of immunosuppression. Prognosis is favourable compared with idiopathic pulmonary fibrosis, although the diagnosis still carries an attributable mortality. Herein we will summarize the clinical characteristics and management of idiopathic NSIP. PMID- 26564812 TI - Layered polymeric nitrogen in RbN3 at high pressures. AB - The structural evolutionary behaviors of nitrogen in RbN3 have been studied up to 300 GPa using a particle swarm optimization structure searching method combined with density functional calculations. Three stable new phases with P-1, P6/mmm and C2/m structure at pressure of 30, 50 and 200 GPa are identified for the first time. The analysis of the crystal structures of three new predicated phases reveals that the transition of N3- ions goes from linear molecules to polymeric chains, benzene-like rings and then to polymeric layers induced by pressure. The electronic structures of three predicted phases reveal that the structural changes are accompanied and driven by the change of orbital hybridization of N atoms from sp to sp(2) and finally to partial sp(3). Most interestingly, the Rb atoms show obvious transition metal-like properties through the occupation of 4d orbitals in high-pressure phases. Moreover, the Rb atoms are characterized by strong hybridization between 4d orbitals of Rb and 2p orbitals of N in C2/m structure. Our studies complete the structural evolution of RbN3 under pressure and reveal for the first time that the Rb atoms in rubidium nitride possess transition element-like properties under pressure. PMID- 26564811 TI - HLA class I downregulation is associated with enhanced NK-cell killing of melanoma cells with acquired drug resistance to BRAF inhibitors. AB - The frequent development of drug resistance to targeted therapies in cancer patients has stimulated interest in strategies counteracting resistance. Combining immunotherapies with targeted therapies is one such strategy. In this context, we asked whether human NK cells can target melanoma cells that have acquired resistance to selective inhibitors targeting activating mutants of the B Raf kinase (BRAF inhibitors, BRAFi). We generated drug-resistant cell variants in vitro from human BRAF-mutant melanoma cell lines MEL-HO, COLO-38, SK-MEL-37, 1520 and from primary melanoma cells freshly isolated from two patients. All drug resistant cell variants remained susceptible to lysis by IL-2-activated NK cells; and two BRAFi-resistant lines (BRAFi-R) became significantly more susceptible to NK-cell lysis than their parental lines. This was associated with significant HLA class I antigen downregulation and PD-L1 upregulation on the drug-resistant lines. Although blocking HLA class I enhanced the extent of lysis of both BRAFi-R and parental cells to NK-cell-mediated lysis, antibody-mediated inhibition of PD1 PD-L1 interactions had no detectable effect. HLA class I antigen expression on BRAFi-R melanoma variants thus appears to play a major role in their susceptibility to NK-cell cytotoxicity. These findings suggest that NK-cell-based immunotherapy may be a viable approach to treat melanoma patients with acquired resistance to BRAF inhibitors. PMID- 26564813 TI - Proof-of-concept: neonatal intravenous injection of adeno-associated virus vectors results in successful transduction of myenteric and submucosal neurons in the mouse small and large intestine. AB - BACKGROUND: Despite the success of viral vector technology in the transduction of the central nervous system in both preclinical research and gene therapy, its potential in neurogastroenterological research remains largely unexploited. This study asked whether and to what extent myenteric and submucosal neurons in the ileum and distal colon of the mouse were transduced after neonatal systemic delivery of recombinant adeno-associated viral vectors (AAVs). METHODS: Mice were intravenously injected at postnatal day one with AAV pseudotypes AAV8 or AAV9 carrying a cassette encoding enhanced green fluorescent protein (eGFP) as a reporter under the control of a cytomegalovirus promoter. At postnatal day 35, transduction of the myenteric and submucosal plexuses of the ileum and distal colon was evaluated in whole-mount preparations, using immunohistochemistry to neurochemically identify transduced enteric neurons. KEY RESULTS: The pseudotypes AAV8 and AAV9 showed equal potential in transducing the enteric nervous system (ENS), with 25-30% of the neurons expressing eGFP. However, the percentage of eGFP-expressing colonic submucosal neurons was significantly lower. Neurochemical analysis showed that all enteric neuron subtypes, but not glia, expressed the reporter protein. Intrinsic sensory neurons were most efficiently transduced as nearly 80% of calcitonin gene-related peptide-positive neurons expressed the transgene. CONCLUSIONS & INFERENCES: The pseudotypes AAV8 and AAV9 can be employed for gene delivery to both the myenteric and the submucosal plexus, although the transduction efficiency in the latter is region-dependent. These findings open perspectives for novel preclinical applications aimed at manipulating and imaging the ENS in the short term, and in gene therapy in the longer term. PMID- 26564814 TI - CD252 regulates mast cell mediated, CD1d-restricted NKT-cell activation in mice. AB - The interaction between tissue-resident mast cells (MCs) and recruited immune cells contributes to tissue immunosurveillance. However, the cells, mechanisms, and receptors involved in this crosstalk remain ill defined. Invariant natural killer T (iNKT) cells are CD1d-restricted innate lymphocytes that recognize glycolipid antigens and have emerged as critical players in immunity. Here, we show that primary mouse peritoneal MCs express surface CD1d, which is upregulated in vivo following administration of alpha-galactosylceramide. In contrast, in BM derived MCs CD1d was found to be stored intracellularly and to relocate at the cell surface upon IgE-mediated degranulation. Activated BM-derived MCs expressing surface CD1d and loaded with alpha-galactosylceramide were found to induce iNKT cell proliferation and the release of IFN-gamma, IL-13, and IL-4 in a CD1d restricted manner. Moreover, the costimulatory molecules CD48, CD137L, CD252, CD274, and CD275 affected MC-induced IFN-gamma release and iNKT-cell proliferation. Interestingly, among the costimulatory molecules, CD48 and CD252 exhibited a distinctly regulatory activity on iNKT-cell release of both IFN-gamma and IL-13. In conclusion, we demonstrate that the crosstalk between MCs and iNKT cells may regulate inflammatory immune responses. PMID- 26564815 TI - Towards an antimicrobial 'microglove'. AB - A large proportion of hospital-related infections are acquired and spread due to the direct contacts between patients and healthcare workers. Accordingly, proper infection prevention measures, and especially hand hygiene, are key to limit the spread of infections in nosocomial settings. However, healthcare workers frequently experience difficulties in complying strictly to hand disinfection protocols. This study was therefore aimed at the development of a hand rub with antimicrobial activity that forms a protective film on the hand, a so-called microglove, in order to enhance hand hygiene. For this purpose, various co polymer formulations consisting of different ratios of Polyvinylpyrrolidone (PVP) and a branched C20 derivatized maleate (M20) in combination with the known biocide benzalkonium chloride (BKC) were tested for their combined film-forming and antimicrobial activities. The results of a series of novel contamination and transmission assays show that a formulation of 80% PVP and 20% M20 co-polymer with 0.9% BKC fulfils the elementary requirements for an antimicrobial microglove. PMID- 26564816 TI - Trends in Nurse Practitioner and Physician Assistant Practice in Nursing Homes, 2000-2010. AB - OBJECTIVE: To examine nurse practitioner (NP) and physician assistant (PA) practice in nursing homes (NHs) during 2000-2010. DATA SOURCES: Data were derived from the Online Survey Certification and Reporting system and Medicare Part B claims (20 percent sample). METHODS: NP/PA state average employment, visit per bed year (VPBY), and providers per NH were examined. State fixed-effect models examined the association between state regulations and NP/PA use. PRINCIPAL FINDINGS: NHs using any NPs/PAs increased from 20.4 to 35.0 percent during 2000 2010. Average NP/PA VPBY increased from 1.0/0.3 to 3.0/0.6 during 2000-2010. Average number of NPs/PAs per NH increased from 0.2/0.09 to 0.5/0.14 during 2000 2010. The impact of state scope-of-practice regulations was mixed. CONCLUSIONS: NP and PA scope-of-practice regulations impact their practice in NHs, not always as intended. PMID- 26564817 TI - Obesity rates in two generations of Swedish women entering pregnancy, and associated obesity risk among adult daughters. AB - We examined changes in obesity rates in two generations of Swedish women entering pregnancy, and assessed the effects of maternal body mass index (BMI) on the risk of overweight or obesity among adult daughters. This study covered an intergenerational retrospective cohort of 26,561 Swedish mothers and their 26,561 first-born daughters. There was a 4-fold increase in obesity rates, which rose from 3.1% among women entering pregnancy in 1982-1988 to 12.3% among their daughters in 2000-2008 (p < 0.0001) when entering pregnancy. The greater the maternal BMI, the greater the odds of overweight and/or obesity among daughters. Underweight mothers had half the odds of having an overweight or obese daughter in comparison to mothers of normal BMI (p < 0.0001). In contrast, the odds ratio of obese mothers having obese daughters was 3.94 (p < 0.0001). This study showed a strong association between maternal obesity and the risk of obesity among their first-born daughters. In addition, we observed a considerable increase in obesity rates across generations in mother-daughter pairs of Swedish women entering pregnancy. Thus, it is important to have preventative strategies in place to halt the worsening intergenerational cycle of obesity. PMID- 26564818 TI - Atherosclerosis Susceptibility in Mice Is Independent of the V1 Immunoglobulin Heavy Chain Gene. AB - OBJECTIVE: The V1 (VHS107.1.42) immunoglobulin heavy chain gene is thought to be critical in producing IgM natural antibodies of the T15-idiotype that protect against both atherosclerosis and infection from Streptococcus pneumoniae. Our aim was to determine whether genetic loss of the V1 gene increased atherosclerotic plaque burden in vivo because of a reduction in the T15-idiotype or other atheroprotective antibodies. APPROACH AND RESULTS: We crossed VHS107.1.42 deficient mice with the atherosclerosis-prone Apoe(-/-) and Ldlr(-/-) strains. Although these double knockout strains manifested no defects in B-cell development, we did observe a substantial reduction in early immune responses against phosphocholine after immunization. However, the titers of plasma antibodies reacting against defined atherosclerotic antigens such as oxidized low density lipoprotein, as well as the T15-idiotype, were unaffected by loss of the VHS107.1.42 gene in hypercholesterolemic mice. Furthermore, we observed no increase in atherosclerotic lesion formation, either within the aortic arch or aortic root. Robust deposition of IgM within atherosclerotic plaques could also be readily observed in both control and experimental mice. CONCLUSIONS: Our data indicate that IgM-dependent protection against atherosclerosis is unlikely to be dependent on antibodies that use the VHS107.1.42 gene, in contrast to the acute immune response conferred by this heavy chain in the response to phosphocholine and in providing resistance against lethal S pneumoniae infection. PMID- 26564819 TI - MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation. AB - OBJECTIVE: Arterial injury stimulates remodeling responses that, when excessive, lead to stenosis. These responses are influenced by integrin signaling in vascular smooth muscle cells (VSMCs). Microfibrillar-associated protein 4 (MFAP4) is an integrin ligand localized to extracellular matrix fibers in the vascular wall. The role of MFAP4 in vascular biology is unknown. We aimed to test the hypothesis that MFAP4 would enhance integrin-dependent VSMC activation. APPROACH AND RESULTS: We produced Mfap4-deficient (Mfap4(-/-)) mice and performed carotid artery ligation to explore the role of MFAP4 in vascular biology in vivo. Furthermore, we investigated the effects of MFAP4 in neointimal formation ex vivo and in primary VSMC and monocyte cultures in vitro. When challenged with carotid artery ligation, Mfap4(-/-) mice exhibited delayed neointimal formation, accompanied by early reduction in the number of proliferating medial and neointimal cells, as well as infiltrating leukocytes. Delayed neointimal formation was associated with decreased cross-sectional area of ligated Mfap4(-/ ) carotid arteries resulting in lumen narrowing 28 days after ligation. MFAP4 blockade prohibited the formation of neointimal hyperplasia ex vivo. Moreover, we demonstrated that MFAP4 is a ligand for integrin alphaVbeta3 and mediates VSMC phosphorylation of focal adhesion kinase, migration, and proliferation in vitro. MFAP4-dependent VSMC activation was reversible by treatment with MFAP4-blocking antibodies and inhibitors of focal adhesion kinase and downstream kinases. In addition, we showed that MFAP4 promotes monocyte chemotaxis in integrin alphaVbeta3-dependent manner. CONCLUSIONS: MFAP4 regulates integrin alphaVbeta3 induced VSMC proliferation and migration, as well as monocyte chemotaxis, and accelerates neointimal hyperplasia after vascular injury. PMID- 26564820 TI - Investigating a Liver Fat: Arterial Stiffening Pathway in Adult and Childhood Obesity. AB - OBJECTIVE: To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. APPROACH AND RESULTS: Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/m(2); percentile 8-100) with no identifiable cardiac risk factors underwent; 1H- magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (beta=0.09; P=0.02), liver fat (beta=2.5; P=0.04), and serum triglyceride (beta=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=-0.35; descending, r=-0.23; abdominal, r=-0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=-0.52; P<0.001) were correlated with liver fat in children. CONCLUSIONS: Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity. PMID- 26564824 TI - VOLCANOLOGY. Fire down below. PMID- 26564822 TI - Climate warning, 50 years later. PMID- 26564825 TI - NUCLEAR POWER. Thorium seen as nuclear's new frontier. PMID- 26564821 TI - Deletion of Periostin Protects Against Atherosclerosis in Mice by Altering Inflammation and Extracellular Matrix Remodeling. AB - OBJECTIVE: Periostin is a secreted protein that can alter extracellular matrix remodeling in response to tissue injury. However, the functional role of periostin in the development of atherosclerotic plaques has yet to be described despite its observed induction in diseased vessels and presence in the serum. APPROACH AND RESULTS: Hyperlipidemic, apolipoprotein E-null mice (ApoE(-/) (-)) were crossed with periostin (Postn(-/-)) gene-deleted mice and placed on a high fat diet for 6 or 14 weeks to induce atherosclerosis. En face analysis of aortas showed significantly decreased lesion areas of ApoE(-/-) Postn(-/-) mice compared with ApoE(-/-) mice, as well as a reduced inflammatory response with less macrophage content. Moreover, diseased aortas from ApoE(-/-) Postn(-/-) mice displayed a disorganized extracellular matrix with less collagen cross linking and smaller fibrotic caps, as well as increased matrix metalloproteinase-2, metalloproteinase-13, and procollagen-lysine, 2-oxoglutarate 5-dioxygenase-1 mRNA expression. Furthermore, the loss of periostin was associated with a switch in vascular smooth muscle cells toward a more proliferative and synthetic phenotype. Mechanistically, the loss of periostin reduced macrophage recruitment by transforming growth factor-beta in cellular migration assays. CONCLUSIONS: These are the first genetic data detailing the function of periostin as a regulator of atherosclerotic lesion formation and progression. The data suggest that periostin could be a therapeutic target for atherosclerotic plaque formation through modulation of the immune response and extracellular matrix remodeling. PMID- 26564826 TI - POLAR SCIENCE. How warming oceans unleashed an ice stream. PMID- 26564827 TI - EVOLUTION. Fossils, cells point to early appearance of the brain. PMID- 26564828 TI - MEDICINE. Cancer research centers pool tumor genome data. PMID- 26564829 TI - CANCER IMMUNOTHERAPY. Baby's leukemia recedes after novel cell therapy. PMID- 26564830 TI - Not guilty as charged. PMID- 26564831 TI - EVOLUTION. One era you are in-the next you are out. PMID- 26564832 TI - ARTIFICIAL PHOTOSYNTHESIS. More efficient together. PMID- 26564833 TI - HISTORY OF SCIENCE. Flow cytometry strikes gold. PMID- 26564834 TI - PHYSICS. To catch and smash charge on the hop. PMID- 26564835 TI - IMMUNOLOGY. Breaching the gut-vascular barrier. PMID- 26564836 TI - GLOBAL CHANGE SCIENCE. Stakeholders in climate science: Beyond lip service? PMID- 26564837 TI - Putting Russia on the genome map. PMID- 26564838 TI - Tempering threats to temperate forests. PMID- 26564839 TI - How to measure sustainable progress. PMID- 26564840 TI - Oceans and Climate. Oceans of change. Introduction. PMID- 26564841 TI - Ghosts of oceans past. PMID- 26564842 TI - Breaking the waves. PMID- 26564843 TI - Moveable feast. PMID- 26564844 TI - The silent services of the world ocean. AB - The most recent comprehensive assessment carried out by the Intergovernmental Panel on Climate Change has concluded that "Human influence on the climate system is clear," a headline statement that was approved by all governments in consensus. This influence will have long-lasting consequences for ecosystems, and the resulting impacts will continue to be felt millennia from now. Although the terrestrial impacts of climate change are readily apparent now and have received widespread public attention, the effects of climate change on the oceans have been relatively invisible. However, the world ocean provides a number of crucial services that are of global significance, all of which come with an increasing price caused by human activities. This needs to be taken into account when considering adaptation to and mitigation of anthropogenic climate change. PMID- 26564845 TI - The deep ocean under climate change. AB - The deep ocean absorbs vast amounts of heat and carbon dioxide, providing a critical buffer to climate change but exposing vulnerable ecosystems to combined stresses of warming, ocean acidification, deoxygenation, and altered food inputs. Resulting changes may threaten biodiversity and compromise key ocean services that maintain a healthy planet and human livelihoods. There exist large gaps in understanding of the physical and ecological feedbacks that will occur. Explicit recognition of deep-ocean climate mitigation and inclusion in adaptation planning by the United Nations Framework Convention on Climate Change (UNFCCC) could help to expand deep-ocean research and observation and to protect the integrity and functions of deep-ocean ecosystems. PMID- 26564846 TI - Warm-water coral reefs and climate change. AB - Coral reefs are highly dynamic ecosystems that are regularly exposed to natural perturbations. Human activities have increased the range, intensity, and frequency of disturbance to reefs. Threats such as overfishing and pollution are being compounded by climate change, notably warming and ocean acidification. Elevated temperatures are driving increasingly frequent bleaching events that can lead to the loss of both coral cover and reef structural complexity. There remains considerable variability in the distribution of threats and in the ability of reefs to survive or recover from such disturbances. Without significant emissions reductions, however, the future of coral reefs is increasingly bleak. PMID- 26564847 TI - Climate change and marine vertebrates. AB - Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species. PMID- 26564848 TI - Climate change in the oceans: Human impacts and responses. AB - Although it has far-reaching consequences for humanity, attention to climate change impacts on the ocean lags behind concern for impacts on the atmosphere and land. Understanding these impacts, as well as society's diverse perspectives and multiscale responses to the changing oceans, requires a correspondingly diverse body of scholarship in the physical, biological, and social sciences and humanities. This can ensure that a plurality of values and viewpoints is reflected in the research that informs climate policy and may enable the concerns of maritime societies and economic sectors to be heard in key adaptation and mitigation discussions. PMID- 26564849 TI - Imaging resonances in low-energy NO-He inelastic collisions. AB - In molecular collisions, resonances occur at specific energies at which the colliding particles temporarily form quasibound complexes, resulting in rapid variations in the energy dependence of scattering cross sections. Experimentally, it has proven challenging to observe such scattering resonances, especially in differential cross sections. We report the observation of resonance fingerprints in the state-to-state differential cross sections for inelastic NO-He collisions in the 13 to 19 centimeter(-1) energy range with 0.3 centimeter(-1) resolution. The observed structures were in excellent agreement with quantum scattering calculations. They were analyzed by separating the resonance contributions to the differential cross sections from the background through a partitioning of the multichannel scattering matrix. This revealed the partial-wave composition of the resonances and their evolution during the collision. PMID- 26564850 TI - Evidence for primordial water in Earth's deep mantle. AB - The hydrogen-isotope [deuterium/hydrogen (D/H)] ratio of Earth can be used to constrain the origin of its water. However, the most accessible reservoir, Earth's oceans, may no longer represent the original (primordial) D/H ratio, owing to changes caused by water cycling between the surface and the interior. Thus, a reservoir completely isolated from surface processes is required to define Earth's original D/H signature. Here we present data for Baffin Island and Icelandic lavas, which suggest that the deep mantle has a low D/H ratio (deltaD more negative than -218 per mil). Such strongly negative values indicate the existence of a component within Earth's interior that inherited its D/H ratio directly from the protosolar nebula. PMID- 26564851 TI - Torque-mixing magnetic resonance spectroscopy. AB - A universal, torque-mixing method for magnetic resonance spectroscopy is presented. In analogy to resonance detection by magnetic induction, the transverse component of a precessing dipole moment can be measured in sensitive broadband spectroscopy, here using a resonant mechanical torque sensor. Unlike induction, the torque amplitude allows equilibrium magnetic properties to be monitored simultaneously with the spin dynamics. Comprehensive electron spin resonance spectra of a single-crystal, mesoscopic yttrium iron garnet disk at room temperature reveal assisted switching between magnetization states and mode dependent spin resonance interactions with nanoscale surface imperfections. The rich detail allows analysis of even complex three-dimensional spin textures. The flexibility of microelectromechanical and optomechanical devices combined with broad generality and capabilities of torque-mixing magnetic resonance spectroscopy offers great opportunities for development of integrated devices. PMID- 26564853 TI - Evolution and dispersal of mammoths across the Northern Hemisphere. AB - Mammoths provide a detailed example of species origins and dispersal, but understanding has been impeded by taxonomic confusion, especially in North America. The Columbian mammoth Mammuthus columbi was thought to have evolved in North America from a more primitive Eurasian immigrant. The earliest American mammoths (1.5 million years ago), however, resemble the advanced Eurasian M. trogontherii that crossed the Bering land bridge around that time, giving rise directly to M. columbi. Woolly mammoth M. primigenius later evolved in Beringia and spread into Europe and North America, leading to a diversity of morphologies as it encountered endemic M. trogontherii and M. columbi, respectively. In North America, this included intermediates ("M. jeffersonii"), suggesting introgression of M. primigenius with M. columbi. The lineage illustrates the dynamic interplay of local adaptation, dispersal, and gene flow in the evolution of a widely distributed species complex. PMID- 26564852 TI - An extremely bright gamma-ray pulsar in the Large Magellanic Cloud. AB - Pulsars are rapidly spinning, highly magnetized neutron stars, created in the gravitational collapse of massive stars. We report the detection of pulsed giga electron volt gamma rays from the young pulsar PSR J0540-6919 in the Large Magellanic Cloud, a satellite galaxy of the Milky Way. This is the first gamma ray pulsar detected in another galaxy. It has the most luminous pulsed gamma-ray emission yet observed, exceeding the Crab pulsar's by a factor of 20. PSR J0540 6919 presents an extreme test case for understanding the structure and evolution of neutron star magnetospheres. PMID- 26564854 TI - Body-size reduction in vertebrates following the end-Devonian mass extinction. AB - Following the end-Devonian mass extinction (359 million years ago), vertebrates experienced persistent reductions in body size for at least 36 million years. Global shrinkage was not related to oxygen or temperature, which suggests that ecological drivers played a key role in determining the length and direction of size trends. Small, fast-breeding ray-finned fishes, sharks, and tetrapods, most under 1 meter in length from snout to tail, radiated to dominate postextinction ecosystems and vertebrae biodiversity. The few large-bodied, slow-breeding survivors failed to diversify, facing extinction despite earlier evolutionary success. Thus, the recovery interval resembled modern ecological successions in terms of active selection on size and related life histories. Disruption of global vertebrate, and particularly fish, biotas may commonly lead to widespread, long-term reduction in body size, structuring future biodiversity. PMID- 26564855 TI - Dynamics of CRISPR-Cas9 genome interrogation in living cells. AB - The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells. We show that three-dimensional diffusion dominates Cas9 searching in vivo, and off-target binding events are, on average, short-lived (<1 second). Searching is dependent on the local chromatin environment, with less sampling and slower movement within heterochromatin. These results reveal how the bacterial Cas9 protein interrogates mammalian genomes and navigates eukaryotic chromatin structure. PMID- 26564856 TI - A gut-vascular barrier controls the systemic dissemination of bacteria. AB - In healthy individuals, the intestinal microbiota cannot access the liver, spleen, or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, and can induce a systemic immune response. How such compartmentalization is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in a manner dependent on its pathogenicity island (Spi) 2 encoded type III secretion system and on decreased beta-catenin-dependent signaling in gut endothelial cells. The GVB is modified in celiac disease patients with elevated serum transaminases, which indicates that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis. PMID- 26564857 TI - Leaping into the unknown. PMID- 26564858 TI - Erratum for the Report "Genomic correlates of response to CTLA-4 blockade in metastatic melanoma" by E. M. Van Allen, D. Miao, B. Schilling, S. A. Shukla, C. Blank, L. Zimmer, A. Sucker, U. Hillen, M. H. Geukes Foppen, S. M. Goldinger, J. Utikal, J. C. Hassel, B. Weide, K. C. Kaehler, C. Loquai, P. Mohr, R. Gutzmer, R. Dummer, S. Gabriel, C. J. Wu, D. Schadendorf, L. A. Garraway. PMID- 26564859 TI - Impulsivity as a precedent factor for problematic Internet use: How can we be sure? AB - Previous research has suggested that problematic Internet use (PIU) is associated with impulse control disorder. Although researchers have suggested that impulsivity is a risk factor for PIU, the literature lacks longitudinal evidence on the relationship between impulsivity and PIU. We aimed to use a cross-lagged analytic framework to identify temporal order effects and hypothesised that impulsivity was the precedent factor for PIU. In a panel sample of college students (N = 367), trait impulsivity and PIU were measured in the spring of freshman year and in their junior year. The measures included a self-developed PIU Scale and the revised Impulsiveness Scale based on Barratt's concept. We found that "non-planning impulsivity" was not associated with PIU. The "motor impulsivity" subfactor was thus adopted in the cross-lagged model. The results suggest that motor impulsivity and PIU were stable across time. Motor impulsivity at Time 1 positively predicted PIU at Time 2, but PIU at Time 1 did not predict motor impulsivity at Time 2. A further investigation using gender as a moderator found a gender difference in the temporal relationship. Because motor impulsivity is a risk factor for PIU, potential prevention strategies based on this result are suggested. PMID- 26564860 TI - The effects of colour and valence on news evaluation. AB - Research across different fields of psychology has reported effects of colour cues on a variety of cognitive processes. Especially, the colour red has been shown to have striking influences. In the context of media reception, however, colour effects have been widely neglected so far. This study made a first step in this direction by investigating the effects of the colour red (compared with blue and grey) on the way news articles are evaluated. Two types of news were framed by a coloured border while the valence of the news content additionally varied. Based on 369 participants who read and evaluated the news articles online, we observed effects for colour cues and news valence in the absence of an interaction effect, indicating that the colour red induced approach motivation. However, only the contrast between red and grey reached statistical significance, indicating that chromatic and achromatic colours may differ in their perceived visual saliency. Overall, these results provide an important complement to previous studies and have practical implications for media researchers and producers. PMID- 26564861 TI - Studying cell biology in the skin. AB - Advances in cell biology have often been driven by studies in diverse organisms and cell types. Although there are technical reasons for why different cell types are used, there are also important physiological reasons. For example, ultrastructural studies of vesicle transport were aided by the use of professional secretory cell types. The use of tissues/primary cells has the advantage not only of using cells that are adapted to the use of certain cell biological machinery, but also of highlighting the physiological roles of this machinery. Here we discuss advantages of the skin as a model system. We discuss both advances in cell biology that used the skin as a driving force and future prospects for use of the skin to understand basic cell biology. A unique combination of characteristics and tools makes the skin a useful in vivo model system for many cell biologists. PMID- 26564863 TI - The effect of motivation and positive affect on ego depletion: Replenishment versus release mechanism. AB - In this study, 2 experiments were conducted to investigate whether motivation and positive affect can alleviate ego depletion and to elucidate their possible mechanisms. In Experiment 1, a crossing-out-letter task was adapted to reach an ego depletion state for Chinese participants. Participants were then randomly assigned to the extrinsic motivation group, the positive affect group or the depletion control group. After the experimental treatment, a dumbbell task was used to measure participants' remaining self-regulatory resources. The results showed that participants in the motivation and positive affect groups performed better on the dumbbell task than participants in the depletion control group. Experiment 2 was similar to Experiment 1 except that participants were asked to perform an additional unexpected dumbbell task after a neutral video following the above procedure. The results of Experiment 1 were replicated; however, participants' performance on the additional dumbbell task differed. The positive affect group performed better than the depletion control group, indicating an increase in self-regulatory resources and thus supporting the replenishment effect of positive affect. No significant difference was found between the motivation group and the depletion control group. PMID- 26564862 TI - Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction. AB - The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the genetic manipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat hearts after myocardial infarction improved cardiac function, and this was related to differentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo and might provide a source of CPCs for regenerative approaches. SIGNIFICANCE: The findings from the present study have demonstrated an efficient protein-transduction method of directly reprogramming fibroblasts into cardiac progenitor cells. These results have great potential in cell-based therapy for cardiovascular diseases. PMID- 26564864 TI - COMPREHENSIVE DATA CONCERNING COSMIC RADIATION DOSES AT GROUND LEVEL AND IN FLIGHTS FOR TURKEY. AB - Cosmic radiation doses of individuals living in 81 cities in Turkey were estimated by using CARI-6 software. Annual cosmic radiation doses of individuals were found to be between 308 and 736 uSv y-1 at ground level. The population weighted annual effective dose from cosmic radiation was determined to be 387 uSv y-1 for Turkey. Cosmic radiation doses on-board for 137 (60 domestic and 77 international) flights varied from 1.2 to 83 uSv. It was estimated that six or over long-route round-trip air travels may cause cosmic radiation dose above the permissible limit for member of the public, i.e. 1 mSv y-1 According to the assumption of flights throughout 800 h on each route, cosmic radiation doses were found to be between 1.0 and 4.8 mSv for aircrew. PMID- 26564865 TI - OVERVIEW OF A DIGITAL TOMOSYNTHESIS DEVELOPMENT: NEW APPROACHES FOR LOW-DOSE CHEST IMAGING. AB - Lung cancer has the highest mortality rate among all cancer types, and it has especially high occurrence in Hungary. Low-dose computed tomography (LDCT) has been proved to be a beneficial screening method for lung cancer, decreasing the mortality rate by 20 %. Because of the intensifying fears from X-ray radiation, there is a need to develop other modalities that might work with less radiation and have similar sensitivity in lung nodule finding. Digital tomosynthesis (DTS) may be such a modality that can be a real alternative to LDCT. The goal of this article is to summarise the first results of a Hungarian project for developing a DTS system extended with a computer-aided detection system. It describes the main approaches applied and the main benefits of using DTS based on the first clinical examinations. PMID- 26564866 TI - BACKGROUND TRACK DENSITY REDUCTION OF 50-HZ-HV ECE-PROCESSED THICK POLYCARBONATE DETECTORS TO IMPROVE LOWER DETECTION LIMIT. AB - A recent novel development of 50-Hz-HV ECE of 1-mm-thick and 250-um-thick polycarbonate track detectors (PCTDs) has proved some promising results for some health physics, dosimetry and ion-beam-related applications. The method while proved having some good characteristics for some applications provided a relatively higher background track density (BGTD) in particular when very high voltages are applied to the PCTDs. In order to decrease the minimum detection limit (MDL) of the PCTDs and to further promote its applications for low dose, the BGTD was reduced by applying a layer removal methodology applying ethylendiamine (EDA). The effects of EDA concentrations (50, 60, 65, 70, 75, 80, 85 and 90 %) in water at room temperature (26 degrees C) and soaking durations up to 100 min at different EDA concentration on BGTD reduction were studied. The thickness of the layer removed from the surface of a PCTD highly depends on the soaking time and EDA concentration; it increases as the EDA concentration increases up to for example 700 um after 2 h of soaking in the EDA solution. After ~10 min of soaking duration at any of the above-stated concentrations, the BGTD reaches its minimum value, a value which differs from concentration to concentration. An EDA concentration of 85 % in water provided the lowest BGTD of 64.06 +/- 3.12 tracks cm- 2; ~6 times lower than that of its original value. It is shown that the layer removal process does not change the registration characteristics of the PCTD and its appearance significantly. The MDL of the PCTDs depends strongly on the BGTD. The MDL values for a desired confidence level were also studied by three calculation methods. The results of the BGTD and the MDL studies under different conditions applied are presented and discussed. PMID- 26564867 TI - MULTI-PARAMETER INTERPOLATION OF BETA RADIATION DOSE RATES USING RADIAL BASIS FUNCTIONS. AB - In this study, the interpolation problem for a set of Monte Carlo simulations of dose rate per activity of beta-emitting radionuclides is considered. The simulations were carried out for various conditions: for circular areal sources of different diameters and radionuclides, and for various distances from the source. Calculations were done for both operational quantities as well as organ doses: Hp(0.07), Hp(3), Hp(10), Hskin and Hlens Interpolation is needed for practical applications because it is often necessary to evaluate the dose quantities at parameter values that do not correspond exactly to the ones that were used for the simulation. To solve this problem, the method of radial basis function thin-plate spline interpolation is used. The method used for the interpolation and a software application called BetaDosim, which allows users to get the interpolated values, are described. BetaDosim is freely available. PMID- 26564870 TI - Defra agrees to cut its spending. PMID- 26564871 TI - New slaughter legislation could compromise poultry welfare, warns BVA. PMID- 26564872 TI - Charities call for a review of the online exotic pet trade. PMID- 26564873 TI - Representative body opposes further restrictions on ketamine. PMID- 26564874 TI - Wales-wide roll out for Cymorth TB. PMID- 26564875 TI - BVA briefs MPs on bovine TB. PMID- 26564876 TI - Network aims to foster collaboration in the animal welfare research community. PMID- 26564877 TI - New clinical research editor for Veterinary Record. PMID- 26564878 TI - Scottish Government seeks views on controls on electronic training collars. PMID- 26564879 TI - Early day motion recognises VN title campaign. PMID- 26564880 TI - Zoo's chief executive named 'business woman of the year'. PMID- 26564881 TI - Journals' podcast collection begins to grow. PMID- 26564882 TI - The importance of pets to families. PMID- 26564883 TI - New facilities to enhance nursing students' access to animals. PMID- 26564884 TI - Guidance on antibiotic use for anaesthetists. PMID- 26564885 TI - Charity to begin work in Botswana. PMID- 26564886 TI - Boost for veterinary nurse bursary fund. PMID- 26564887 TI - Northern Ireland disease surveillance report, July to September 2015. AB - Endocarditis in a cow. Blackleg in unvaccinated calves. Copper poisoning in pedigree sheep. Malignant oedema in a ram. Salmonellosis in fattening pigs. Fungal pneumonia and airsacculitis in turkeys. Coccidiosis and Marek's disease in gamebirds. These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for July to September 2015. PMID- 26564888 TI - Taking action to reduce the risk of copper toxicity in cattle. PMID- 26564889 TI - Shortage of experienced vets. PMID- 26564890 TI - Canine epileptoid cramping syndrome in border terriers. PMID- 26564892 TI - Correction. PMID- 26564891 TI - Shorter sentences. PMID- 26564893 TI - Cattle ear tag to facilitate multiple testing of tissue samples. PMID- 26564894 TI - Injectable oxytocin. PMID- 26564895 TI - Online ordering for microchips. PMID- 26564896 TI - Pursuing a career in veterinary public health. AB - Milorad Radakovic is a teaching fellow in veterinary public health (VPH) at the University of Cambridge. Here, he explains why he believes the challenges in this field of veterinary medicine make for an exciting career path. In a second article to be published in Vet Record Careers next week, he will share some of his own experiences of working in this field. PMID- 26564897 TI - Ten-minute chat. AB - Pete Matthews works in mixed practice at Galedin Veterinary in the Scottish Borders. He has been a member of the Tweed Valley Mountain Rescue Team for eight years and last year took on the role of team leader for a three-year term. PMID- 26564898 TI - Self-Evaluation of Negative Symptoms: A Novel Tool to Assess Negative Symptoms. AB - Many patients with schizophrenia have negative symptoms, but their evaluation is a challenge. Thus, standardized assessments are needed to facilitate identification of these symptoms. Many tools have been developed, but most are based on observer ratings. Self-evaluation can provide an additional outcome measure and allow patients to be more engaged in their treatment. The aim of this study was to present a novel tool, Self-evaluation of Negative Symptoms (SNS), and demonstrate its validity. Forty-nine patients with schizophrenia and schizoaffective disorders according to DSM-5 were evaluated. Cronbach's coefficient (alpha = 0.867) showed good internal consistency. Factor analysis extracted 2 factors (apathy and emotional) that accounted for 75.2% of the variance. The SNS significantly correlated with the Scale of Assessment of Negative Symptoms (r= 0.628) and the Clinician Global Impression on the severity of negative symptoms (r= 0.599), supporting good convergent validity. SNS scores did not correlate with level of insight (r= 0.008), Parkinsonism (r= 0.175) or Brief Psychiatric Rating Scale positive subscores (r= 0.253), which indicates good discriminant validity. The intrasubject reliability of the SNS revealed excellent intraclass correlation coefficients (ICC = 0.942). Taken together, the results show that the SNS has good psychometric properties and satisfactory acceptance by patients. The study also demonstrates the ability of patients with schizophrenia to accurately report their own experiences. Self-assessments of negative symptoms should be more widely employed in clinical practice because they may allow patients with schizophrenia to develop appropriate coping strategies. PMID- 26564899 TI - An Arbitrary Line in the Sand: Rising Scientists Confront the Impact Factor. PMID- 26564901 TI - A Comment on Fine-Scale Heterogeneity in Crossover Rate in the garnet-scalloped Region of the Drosophila melanogaster X Chromosome. PMID- 26564903 TI - Osteoclast activation and sickle bone disease. PMID- 26564904 TI - Lucky 13. PMID- 26564900 TI - Genetics on the Fly: A Primer on the Drosophila Model System. AB - Fruit flies of the genus Drosophila have been an attractive and effective genetic model organism since Thomas Hunt Morgan and colleagues made seminal discoveries with them a century ago. Work with Drosophila has enabled dramatic advances in cell and developmental biology, neurobiology and behavior, molecular biology, evolutionary and population genetics, and other fields. With more tissue types and observable behaviors than in other short-generation model organisms, and with vast genome data available for many species within the genus, the fly's tractable complexity will continue to enable exciting opportunities to explore mechanisms of complex developmental programs, behaviors, and broader evolutionary questions. This primer describes the organism's natural history, the features of sequenced genomes within the genus, the wide range of available genetic tools and online resources, the types of biological questions Drosophila can help address, and historical milestones. PMID- 26564905 TI - Free hemoglobin: a boost to platelet thrombi. PMID- 26564906 TI - The cis-regulatory code of Hox function in Drosophila. PMID- 26564909 TI - Trauma-Informed Care in the Massachusetts Child Trauma Project. AB - Child maltreatment is a serious public health concern, and its detrimental effects can be compounded by traumatic experiences associated with the child welfare (CW) system. Trauma-informed care (TIC) is a promising strategy for addressing traumatized children's needs, but research on the impact of TIC in CW is limited. This study examines initial findings of the Massachusetts Child Trauma Project, a statewide TIC initiative in the CW system and mental health network. After 1 year of implementation, Trauma-Informed Leadership Teams in CW offices emerged as key structures for TIC systems integration, and mental health providers' participation in evidence-based treatment (EBT) learning collaboratives was linked to improvements in trauma-informed individual and agency practices. After approximately 6 months of EBT treatment, children had fewer posttraumatic symptoms and behavior problems compared to baseline. Barriers to TIC that emerged included scarce resources for trauma-related work in the CW agency and few mental providers providing EBTs to young children. Future research might explore variations in TIC across service system components as well as the potential for differential effects across EBT models disseminated through TIC. PMID- 26564908 TI - ApoE4 upregulates the activity of mitochondria-associated ER membranes. AB - In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin-deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the epsilon4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte-conditioned media (ACM) model, we now show that ER-mitochondrial communication and MAM function-as measured by the synthesis of phospholipids and of cholesteryl esters, respectively-are increased significantly in cells treated with ApoE4-containing ACM as compared to those treated with ApoE3-containing ACM. Notably, this effect was seen with lipoprotein-enriched preparations, but not with lipid-free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease. PMID- 26564910 TI - The Growing Burden of Neonatal Opiate Exposure on Children and Family Services in Massachusetts. AB - Increasing opiate use among women of reproductive age has led to a rise in adverse pregnancy outcomes, including neonatal abstinence syndrome (NAS). Recent studies have documented the increased incidence of NAS, but subsequent impact on the chain of organizations within the social service system remains unexplored. In this article, we begin to estimate the reach of this issue by assessing the labor costs of caring for NAS infants within the Massachusetts Department of Children and Families (MA DCF). Based on a process map of services, we modeled social service hours using encounter-level hospital data as inputs. In this manner, we estimate that MA DCF professionals now devote more than 10,000 hours per month to this single problem. As opiate addiction increases across America, substantial additional investment in social service providers, foster care, Early Intervention Programs, and other family services will be required. PMID- 26564912 TI - Treatment Modalities for Small Saphenous Vein Insufficiency: Systematic Review and Meta-analysis. AB - PURPOSE: To investigate and compare the anatomical success rates and complications of the treatment modalities for small saphenous vein (SSV) incompetence. METHODS: A systematic literature search was performed in PubMed, EMBASE, and the Cochrane Library on the following therapies for incompetence of SSVs: surgery, endovenous laser ablation (EVLA), radiofrequency ablation (RFA), ultrasound-guided foam sclerotherapy (UGFS), steam ablation, and mechanochemical endovenous ablation (MOCA). The search found 49 articles (5 randomized controlled trials, 44 cohort studies) reporting on the different treatment modalities: surgery (n=9), EVLA (n=28), RFA (n=9), UGFS (n=6), and MOCA (n=1). A random effects model was used to estimate the primary outcome of anatomical success, which was defined as closure of the treated vein on follow-up duplex ultrasound imaging. The estimate is reported with the 95% confidence interval (CI). Secondary outcomes were technical success and major complications [paresthesia and deep vein thrombosis (DVT)], given as the weighted means. RESULTS: The pooled anatomical success rate was 58.0% (95% CI 40.9% to 75.0%) for surgery in 798 SSVs, 98.5% (95% CI 97.7% to 99.2%) for EVLA in 2950 SSVs, 97.1% (95% CI 94.3% to 99.9%) for RFA in 386 SSVs, and 63.6% (95% CI 47.1% to 80.1%) for UGFS in 494 SSVs. One study reported results of MOCA, with an anatomical success rate of 94%. Neurologic complications were most frequently reported after surgery (mean 19.6%) and thermal ablation (EVLA: mean 4.8%; RFA: mean 9.7%). Deep venous thrombosis was a rare complication (0% to 1.2%). CONCLUSION: Endovenous thermal ablation (EVLA/RFA) should be preferred to surgery and foam sclerotherapy in the treatment of SSV incompetence. Although data on nonthermal techniques in SSV are still sparse, the potential benefits, especially the reduced risk of nerve injury, might be of considerable clinical importance. PMID- 26564913 TI - Imaging After Nellix Endovascular Aneurysm Sealing: A Consensus Document. AB - Endovascular aneurysm sealing (EVAS) using the Nellix system is a new and different method of abdominal aortic aneurysm repair. Normal postoperative imaging has unique appearances that change with time; complications also have different and specific appearances. This consensus document on the imaging findings after Nellix EVAS is based on the collective experience of the sites involved in the Nellix EVAS Global Forward Registry and the US Investigational Device Exemption Trial. The normal findings on computed tomography (CT), duplex ultrasound, magnetic resonance imaging, and plain radiography are described. With time, endobag appearances change on CT due to contrast migration to the margins of the hydrogel polymer within the endobag. Air within the endobag also has unique appearances that change over time. Among the complications after Nellix EVAS, type I endoleak usually presents as a curvilinear area of flow between the endobag and aortic wall, while type II endoleak is typically small and usually occurs where an aortic branch artery lies adjacent to an irregular aortic blood lumen that is not completely filled by the endobag. Procedural aortic injury is an uncommon but important complication that occurs as a result of overfilling of the endobags during Nellix EVAS. The optimum imaging surveillance algorithm after Nellix EVAS has yet to be defined but is largely CT-based, especially in the first year postprocedure. However, duplex ultrasound also appears to be a sensitive modality in identifying normal appearances and complications. PMID- 26564914 TI - Type IIIb Endoleak With the Endurant Stent-Graft. AB - PURPOSE: To report 2 cases of type IIIb endoleak with the Endurant stent-graft and postulate the cause for the events. CASE REPORT: A type IIIb endoleak was diagnosed at open conversion for a ruptured aneurysm 4 years after implantation of an Endurant stent-graft. In the other case, the endoleak was diagnosed at angiography 4 years after the Endurant stent-graft was implanted; the stent-graft was relined. In both cases the fabric hole was in the body of the stent-graft at the level of the top of the contralateral limb. CONCLUSION: The cause of the type IIIb endoleaks in these cases was fabric erosion likely due to interaction between the bare metal at the top of the contralateral limb and the fabric of the stent-graft body. PMID- 26564915 TI - Dermatophyte surveillance in cats in three animal shelters in Ontario, Canada. AB - Objectives The aim of the study was to determine the prevalence of dermatophyte shedding in cats admitted to three Ontario animal shelters from February to May 2013. Methods Four hundred cats were sampled within 48 h of admission, using a standard toothbrush sampling technique. Dermatophyte culture was performed. Results Dermatophytes were not identified in any of the 400 cats (0-0.9% one sided exact 97.5% confidence interval). Conclusions and relevance These results imply that dermatophyte shedding is rare in cats admitted to Ontario animal shelters. Consequently, identification of infected animals, particularly multiple animals, represents an unusual occurrence that may justify prompt and intensive control measures. PMID- 26564916 TI - Differences between dorsal and volar dislocations of the distal interphalangeal joint of fingers: a report of 30 cases. PMID- 26564907 TI - Histone demethylases in chromatin biology and beyond. AB - Histone methylation plays fundamental roles in regulating chromatin-based processes. With the discovery of histone demethylases over a decade ago, it is now clear that histone methylation is dynamically regulated to shape the epigenome and regulate important nuclear processes including transcription, cell cycle control and DNA repair. In addition, recent observations suggest that these enzymes could also have functions beyond their originally proposed role as histone demethylases. In this review, we focus on recent advances in our understanding of the molecular mechanisms that underpin the role of histone demethylases in a wide variety of normal cellular processes. PMID- 26564917 TI - Maintaining Microclimates during Nanoliter Chemical Dispensations Using Custom Designed Source Plate Lids. AB - A method is described for using custom snap-on lids to protect chemicals in microtiter plates from evaporation and contamination. The lids contain apertures (diameter 1.5, 1.0, or 0.5 mm) through which the chemical building blocks can be transferred. The lid with 0.5 mm apertures was tested using a noncontact acoustic liquid handler; the 1.0 and 1.5 mm lids were tested using two tip-based liquid handlers. All of the lids reduced the rate at which solvents evaporated to room air, and greatly reduced the rate of contamination by water and oxygen from room air. In steady-state measurements, the lids reduced the rate of evaporation of methanol, 1-hexene, and water by 33% to 248%. In cycled experiments, the contamination of aqueous solvent with oxygen was reduced below detectability and the rate at which DMSO engorged atmospheric water was reduced by 81%. Our results demonstrate that the lids preserve the integrity of air-sensitive reagents during the time needed for different types of liquid handlers to perform dispensations. Controlling degradation and evaporation of chemical building blocks exposed to the atmosphere is increasingly useful as the reagent volume is reduced by advances in liquid handling technology, such as acoustic droplet ejection. PMID- 26564918 TI - A History of Orthoptics in the United States, Part I: "If You Build It, They Will Come". AB - The year 2015 marks the 75th anniversary of the American Association of Certified Orthoptists (AACO), the second oldest orthoptic professional organization in the world. Since its inception, October 7, 1940, approximately 90% of all certified orthoptists (C.O.) have consistently maintained membership in their professional society. Approximately 80% of AACO members attend AACO-sponsored scientific meetings at least once annually. And 17-20% of members are actively involved in AACO leadership, management, and activities.Eye care has changed dramatically over the last 75 years, and orthoptics has successfully adapted to survive due to the fortitude and resilience of its practitioners. The AACO has weathered opposition from much more powerful competitors, ever-increasing health care regulation, and an evolution in the standard management of strabismus, only to emerge transformed and even more durable. One constant remains: the qualities that inspired thirty-three individuals to create a profession and a society dedicated to the care of patients with strabismus and disorders of binocular vision, and the education of parents, orthoptists, and ophthalmologists exist in every orthoptist today. These qualities are determination, creativity, dedication, and passion. PMID- 26564919 TI - Pediatric Ophthalmology Practice Efficiency: Utilization of Orthoptists as Partners in the Pediatric Eye Care Team. AB - BACKGROUND AND PURPOSE: The profession of orthoptics has been present for over 100 years and was created as a partnership with pediatric ophthalmology in an effort to provide better strabismus care to children. Orthoptists are known to improve practice efficiency, but to date, no quantitative data has been presented in the literature to support this claim. Proper utilization of an orthoptist is critical to improving practice efficiency and revenue. METHODS: Over a 6-month period, the financial impact to a pediatric ophthalmology practice by the addition of a second certified orthoptist (C.O.) was analyzed. Both indirect and direct income and expenses were considered. RESULTS: Despite their increased salary compared to an ophthalmic assistant, the utilization of an orthoptist provides considerable return on investment. The addition of a certified orthoptist increased practice revenue by over $70,000. CONCLUSION: The addition of a certified orthoptist in a physician's practice significantly increases practice revenue generated. When considering models of healthcare within ophthalmology, the use of an orthoptist as a physician extender has been shown to improve practice efficiency in a cost-effective manner. PMID- 26564921 TI - Torsional Diplopia. AB - BACKGROUND AND PURPOSE: Torsional diplopia can result in failure of fusion in an individual without a measureable strabismus. When presented with a patient with complaints of binocular diplopia, physicians and orthoptists should consider cyclovertical muscle dysfunction when the source of the complaint is not readily apparent. METHODS: A thorough review of the literature combined with the author's own personal experience in treating adult patients with strabismus was used to evaluate the different potential causes of torsional diplopia. Predisposing factors, diagnostic techniques, and strabismus diagnoses are considered. RESULTS: The most common cause of torsional diplopia is a superior oblique palsy. Other more common causes include thyroid-related orbitopathy and skew deviations. CONCLUSIONS: Torsional diplopia is a common cause of undiagnosed strabismus in the adult patient population. Proper consideration of the most common causes should be made. PMID- 26564922 TI - Macular Diplopia. AB - Maculopathies affect point-to-point foveal correspondence causing diplopia. The effect that the maculopathies have on the interaction of central sensory fusion and peripheral fusion are different than the usual understanding of treatment for diplopia. This paper reviews the pathophysiology of macular diplopia, describes the binocular pathology causing the diplopia, discusses the clinical evaluation, and reviews the present treatments including some newer treatment techniques. PMID- 26564923 TI - Small Deviations: Vertical, Horizontal, and Combined. AB - INTRODUCTION AND PURPOSE: Symptomatic, small-angle strabismus is largely an acquired problem of adults that has previously been managed with prism spectacles. This paper will explore surgical options that are becoming increasingly popular. METHODS: The special issues that confound surgical treatment of small-angle strabismus are considered. Surgical procedures described in the literature and in the author's experience that address these issues are reviewed. RESULTS: Several recently described surgical techniques show promise for treatment of small-angle strabismus in adults. Their use is illustrated in a case report. Review of the author's practice shows a rapid increase in surgery for small-angle strabismus. CONCLUSIONS: Surgical strategies for small deviations are increasingly important to meet the spectacle-free expectations of our adult patients. PMID- 26564924 TI - Divergence Insufficiency Esotropia: Surgical Treatment. AB - Divergence insufficiency esotropia, or acquired comitant esotropia that is at least 10Delta larger at distance than at near, is most often seen in older adults, and may also be known as "age-related distance esotropia." Surgical treatment is often indicated for patients who do not tolerate prism therapy, or for those with large angles of esotropia. Surgical treatments have evolved with our understanding of the disease-state. Currently, accepted treatments include lateral rectus resection and medial rectus recession. These surgeries can be performed unilaterally or bilaterally. New surgical techniques such as lateral rectus equatorial myopexy are under investigation and may hold promise as future therapies. PMID- 26564925 TI - Evaluation and Prism Management of Divergence Insufficiency Esotropia. AB - An esodeviation that is greater at distance than near in an adult patient requires a full sensorimotor exam to rule out any cofounding neurological conditions. Many etiologies are described in the literature to cause an esodeviation that is greater at distance than near in adult patients and some exist in conjunction with a neurological condition. However, many adult patients present to the adult strabismus clinic with no other findings on exam and have a purely benign divergence insufficiency esotropia. A review of the literature on divergence insufficiency reveals a few attempts of classifying these entities, but none have been completely accepted.Recently benign non-neurological divergence insufficiency esotropia has been described as a resulting condition due to a mechanical etiology. Currently, the literature only describes a couple of different etiologies.Regardless of the etiology, these patients are quite symptomatic and present to the adult strabismus clinic with various complaints and require a thorough examination. The primary focus of the exam is to first rule out the need for further neurological work-up, but secondly, to also determine the best treatment option for the patient. To determine the best treatment plan, a thorough evaluation, including a sensorimotor exam with proper testing, can help. Many of these patients do very well with base-out prism management; however, some have decompensated to a larger angle and prefer surgical intervention. However, the focus of this paper will be on nonsurgical prism management of patients with divergence insufficiency that is not associated with any neurological disorder. PMID- 26564926 TI - Prism Management in Patients with Neurodegenerative Disease. AB - Patients with motility problems due to neurodegenerative disease such as Parkinson's and its variations often present challenging cases for the orthoptist. A few "tricks of the trade" will be presented on how to make a Parkinson's patient's daily life a little easier. PMID- 26564927 TI - Sensorimotor Characteristics of Neuro-Ophthalmology and Oculo-Plastics Patients. AB - BACKGROUND AND PURPOSE: Certified orthoptists are routinely required, as a standard component of outpatient care, to examine and identify the cause of double vision described by neuro-ophthalmology and oculo-plastics patients. Peer reviewed articles in the strabismus literature describing the significance of this role of the orthoptists, especially in more complex cases of strabismus, do exist, but are outdated. The importance of creating a differential diagnosis in the understanding of the disease process is a well-recognized component of medical education and modern medicine. PATIENTS AND METHOD: This work was a retrospective chart review and descriptive study of the most common clinical characteristics of adult neuro-ophthalmology and oculo-plastics patients seen over a 9-year period by an orthoptist in a large, urban academic institution in the United States. History and clinical data obtained included demographic information; whether the subjects were neuro-ophthalmology or oculo-plastic patients or both; chief complaint; past medical history and associated medical risk factors; past ocular history of strabismus or amblyopia; whether reported diplopia was monocular or binocular; visual acuities; sensorimotor examination and fusion status information; presence or absence of ptosis; pupil size and reactivity; basic accommodative function; orthoptist and physician diagnoses; and suggested treatment of diplopia. RESULTS: Five hundred seventy-five subjects were identified based on inclusion criteria. Racial demographics matched that of the state of Maryland, with the majority of the patients being Caucasian. The minority were of Hispanic origin. Ninety-one percent of the study cohort was referred by the department of neuro-ophthalmology at the institution. Hypertension was a statistically significant medical risk factor for acquired strabismus and diplopia in this adult cohort. Etiology for the strabismus and associated diplopia suggested by the orthoptist was in close agreement with the final diagnosis made by the referring physician. Pupil-sparing oculomotor palsy (third cranial nerve, CN3) occurred as frequently as pupil-involving CN3, with tumor occurring more frequently as an etiology than aneurysm in both groups. Trochlear nerve palsy (CN4) was more often associated with hydrocephalus than abducens nerve palsy (CN6), and trauma remained a common association with acquired CN4 palsy. In patients with thyroid eye disease (TED), eso- and exo deviations occurred with similar frequency. As has been reported in the literature, concomitant myasthenia gravis (MG) remained rare in these patients, although occurring with similar frequency in patients with both types of horizontal deviation. In patients with ptosis, asymmetry was not statistically more predictive of MG than symmetry. Prism was used most frequently, followed by surgery, to address diplopia symptoms. Lastly, there was a statistically significant association of acquired strabismus and diplopia in female subjects with breast cancer and no past ocular history of childhood strabismus or amblyopia. CONCLUSION: The thorough assessment of sensorimotor function, fusion, and visual acuity provided by the orthoptist is an important clinical adjunct in developing the differential required to make an accurate final diagnosis, which sometimes may not subscribe to accepted clinical norms reported in the literature. The orthoptist also plays an important role in the nonsurgical treatment of acquired diplopia due to strabismus. Fresnel Press-OnTM or ground-in spectacle prism was a commonly used treatment for diplopia. PMID- 26564928 TI - Congenital and Genetic Ocular Motility Disorders: Update and Considerations. AB - Concepts regarding certain forms of congenital eye movement disorders have recently changed, due in large part to new genetic evidence identifying causative genes and their role in the development of extraocular muscle innervation. This group is now referred to as the Congenital Cranial Dysinnervation Disorders (CCDDs). Careful assessment of phenotypic features that include both ophthalmological and non-ophthalmological features in genetically defined individuals has led to the development of a more robust classification system. Correlating phenotypes with new genetically defined syndromes has improved the ability of the clinician/researcher to better determine a definitive diagnosis in patients with complex ocular motility disorders. Nevertheless, more work is still required. PMID- 26564929 TI - Evaluation of Sensory Dominance Using Binocular Rivalry as Related to Ocular Deviations. AB - INTRODUCTION AND PURPOSE: To investigate the relationship between sensory dominance and ocular deviations. PATIENTS AND METHODS: Sixty-three patients were evaluated with a new device for the measurement of exclusive visibility during binocular rivalry. The patients were consisted of twenty-three with exotropia (XT), twenty with intermittent exotropia [X(T)], twenty with exophoria (XP), respectively. Device is composed of two retinometers, their holders in which angle and position can be adjustable and a PC for data storage and analysis. In each of eyes, exclusive visibility of one stimulus during binocular rivalry was measured for 60 sec, and the strength of ocular dominance was evaluated by the difference of exclusive visibility between dominant and nondominant eye. RESULTS: The difference of exclusive visibility time between dominant and nondominant eye were 9.8+/-3.7 sec in the XT group, 6.1+/-4.1 sec in the X(T) group and 2.2+/-1.5 sec in the XP group, respectively. There were significant differences between XT and X(T) (P<0.01) as well as between XT and XP (P<0.001). CONCLUSIONS: The present result indicates that sensory dominance was obviously influenced by ocular deviations since exclusive visibility of dominant eye was prolonged with decreasing the opportunity of normal binocular vision such as XT or X(T). PMID- 26564930 TI - Tenacious Proximal Fusion: The Scobee Phenomenon. AB - BACKGROUND AND PURPOSE: When patients with intermittent exotropia show an increase in their near deviation after prolonged monocular occlusion, they have been said to have tenacious proximal fusion (TPF). That term is not adequately descriptive, since this finding can occur without the patient having been allowed to fuse. The purpose of this study is to investigate the possibility that this phenomenon is mediated by the preponderance of binasal retinal disparity and uncrossed localization that occurs with near fixation. PATIENTS AND METHODS: Ten patients with intermittent exotropia who manifested TPF were measured at 6 m, 1/3 m, again at 1/3 m after 1 hour of monocular occlusion, and at 1/3 m with a peripheral crossed localization stimulating device (PCLSD) that simulated the retinal bitemporal disparity and peripheral crossed localization usually found with distance fixation. RESULTS: For the ten patients, the mean measurement at distance was 28.3Delta+/-3.1, initially at near was 4Delta+/-3.9, at near after prolonged monocular occlusion was 25.3Delta+/-5.3, and at near with the PCLSD was 18.5Delta+/-4.1. The differences between the initial near measurement and the measurement with the PCLSD, and between the PCLSD and post-prolonged monocular occlusion were significant with P<0.001 and P=0.0049, respectively. CONCLUSIONS: What has been previously referred to as TPF in fact appears to be convergence induced by the preponderance of binasal retinal disparity and/or peripheral uncrossed localization typically found with near fixation. For simplicity, I propose the term TPF should be replaced with the "Scobee Phenomenon." PMID- 26564931 TI - Unmasking Bilateral Inferior Rectus Restriction in Thyroid Eye Disease: Using Degree of Cyclotropia. AB - PURPOSE: Thyroid eye disease (TED) frequently causes strabismus and diplopia. Though the condition involves multiple extraocular muscles in both eyes, the inferior rectus (IR) muscle is particularly susceptible. TED may be so asymmetric as to mask the involvement of the contralateral IR. The purpose of this study was to determine if the degree of preoperative cyclotropia measured with an objective test could be used to predict the extent of bilateral IR disease and assist in surgical planning. METHODS: Adults with TED involving the IR and demonstrating cyclotropia were enrolled. Preoperative and postoperative sensorimotor exam included quantification of cyclotropia using double Maddox rod test (DMR). Forced ductions were done intraoperatively. Degree of cyclotropia was compared to results of duction tests and surgical outcome. RESULTS: Twelve participating patients demonstrated excyclotropia on DMR test preoperatively (mean 16+/-9 degrees ). Unilateral IR recession was planned based on the results of preoperative ocular rotations and forced duction testing in eight cases. The remaining four underwent bilateral IR recession. Four of the unilateral recession cases presented with reversal of the hypotropia, obvious limitation of elevation in the unoperated eye, and persistent symptomatic excyclotropia at the first postoperative visit. The mean excyclotropia of the bilateral cases was 21+/-5 degrees , compared to 5.5+/-3 degrees in the unilateral group (P<0.005). CONCLUSIONS: Prism diopters of hypotropia, limitation of elevation, and forced duction testing evaluate muscle function relative to its yoke and may underestimate contralateral IR involvement in the case of asymmetrical disease. Duction testing and forced ductions are qualitative and subjective. Results suggest that degree of excyclotropia correlates well with severity of IR restriction, and that amounts exceeding 15 degrees infer bilateral IR involvement. PMID- 26564932 TI - Residual Strabismus in Children Following Improvement of Cranial Nerve Palsies Affecting Ocular Ductions. AB - BACKGROUND: Children with brain neoplasms often develop cranial nerve palsies (CNP) affecting ocular ductions. Duction deficits may improve or resolve with treatment of their intracranial disease. However, these children may be left with residual strabismus. METHODS: We identified 104 children with third, fourth, and/or sixth cranial nerve palsies who were treated for central nervous system (CNS) neoplasms. A retrospective chart review was conducted to determine the presence or absence of residual strabismus following resolution of duction deficits. RESULTS: Of the 104 children with CNP secondary to an intracranial neoplasm, forty-five had improvement or resolution of their duction deficit with treatment of their CNS lesion. Of these forty-five children, one had a third cranial nerve palsy, six had fouth cranial nerve palsies (one was bilateral), thirty-seven had sixth cranial nerve palsies (thirteen were bilateral), and one had two different cranial nerve palsies in the same eye (fourth and sixth). Of the eighteen children with improved (but not resolved) duction deficits, only three (17%) experienced resolution of their strabismus. Of the twenty-seven children with resolved duction deficits, nine (33%) experienced resolution of their strabismus. For the children with residual strabismus, the average angle of strabismus before duction deficits improved or resolved was 33.2Delta; while for those children without residual strabismus, it was 20Delta. CONCLUSIONS: Our findings indicated that the majority of children with improved or resolved duction deficits from CNP after treatment for CNS neoplasms are left with residual strabismus. Therefore, we suggest children with CNP secondary to CNS neoplasms need ophthalmic care after duction deficits resolve, as they are likely to have residual strabismus. PMID- 26564933 TI - Comparing Visual Acuity Measured by Lea Symbols and Patti Pics. AB - INTRODUCTION: There is little data validating most illiterate eye charts. Lea Symbols(r), however, have been well validated in numerous studies. In this study, we compare the assessment of visual acuity employing both the Lea Symbol hanging wall Early Treatment Diabetic Retinopathy Study (ETDRS)-style chart and a similar Patti Pics(r) ETDRS-style chart in order to determine whether the two charts provide clinically similar data. METHODS: We tested the vision of the right eyes of fifty-two consecutive patients. Patients were cooperative children or adults between the ages of 3 and 88 years (mean 58 years). We alternated the order of the chart used first. Patients were also categorized by age and by visual acuity. RESULTS: The visual acuities measured by the two charts were equal for 83% of the measurements (forty-three eyes). In 8% of eyes (four eyes), the visual acuity measured with the Lea Symbols was one line better than that measured by the Patti Pics; in 9% of eyes (five eyes), the acuity from the Patti Pics chart measured one line better than the Lea Symbols. There was no difference in measurements for either adults or children or among patients with different visual acuities. CONCLUSION: We believe this study will serve to provide useful information when choosing an eye chart to assess visual acuity in a clinic setting. Patti Pics performed similarly to Lea Symbols in adults and children tested in a multi specialty ophthalmology practice. We suspect that it would also perform similarly in the primary care and school settings. PMID- 26564934 TI - Is The Convergence Insufficiency Symptom Survey Specific for Convergence Insufficiency? A Prospective, Randomized Study. AB - BACKGROUND AND PURPOSE: The Convergence Insufficiency Symptom Survey (CISS) is a questionnaire used as an outcome measure in treatment of convergence insufficiency. The current prospective randomized trial evaluates the diagnostic specificity of the CISS. PATIENTS AND METHODS: Surveys were completed by 118 adolescent patients who presented for routine eye examinations. Scores were compared between patients who could be classified as having convergence insufficiency (CI) or normal binocular vision (NBV). In addition, a comparison was done between self-and practitioner-administered CISS scores within these groups. RESULTS: The mean CISS score did not differ significantly between NBV patients (14.1+/-11.3, range of 0 to 43) and CI patients (12.3+/-6.7, range of 3 to 28); P=0.32. Mean CISS scores were lower when physician-administered (11.4+/ 7.9) than when self-administered (16.3+/-11.4); P=0.007. CONCLUSION: CISS scores tend to be higher when self-vs. practitioner-administered. This study suggests that the CISS questionnaire is not specific for convergence insufficiency. PMID- 26564935 TI - Wernicke Encephalopathy. AB - INTRODUCTION AND PURPOSE: This paper reviews the complaints and associated symptoms/consequences of lacking essential nutrients and vitamins in our central and peripheral nervous systems. This has become important as there has been a rise in malnutrition following the increasing incidence of bariatric surgery for obesity. METHODS: A case report example involving review of the clinical presentation and treatment. RESULTS: A 30-year-old Caucasian woman who had gastric sleeve surgery did not take the recommended capsules as they were too large to swallow. She noted diplopia and oscillopsia 2 months later, which led her to have full orthoptic and neuro-ophthalmic evaluations. After being treated with chewable vitamins with thiamine, she noted a tremendous improvement in her symptoms. CONCLUSION: Wernicke encephalopathy is a disease that was seen more in the 1940s and 1950s, following war times and mostly in underdeveloped countries. However, with the increasing utilization of bariatric surgery for obesity, neurological offices are seeing more patients with neurological impairments. We recommend inquiring about any obesity surgery in one's history and including Wernicke encephalopathy in possible differential diagnoses in those patients who have a recent onset of strabismus or nystagmus, altered mental status, and/or gait ataxia. PMID- 26564936 TI - A Case Report: Consecutive Cranial Neuropathies Following the Use of Phosphodiesterase-5 Inhibitors. AB - We report a patient who suffered consecutive cranial neuropathies where each event was immediately preceded by the use of oral PDE-5 inhibitors. A discussion of the etiology of the events including possible interaction with other medications is included. PMID- 26564937 TI - A Case Series: Exercise-Induced Esotropia. AB - The authors present three patients with idiopathic exercise-induced esotropia. The history, physical findings, and testing that led to the diagnosis are discussed. To the authors' knowledge, this is the largest series of patients with this rare condition, with this series representing half of reported patients in the literature. It is hoped that a discussion of common features of the condition will guide further exploration of the etiology. PMID- 26564938 TI - Historical Vignette: Robert Marcus Gunn (1850-1909): Scottish Ophthalmologist, Skilled Observer, and Gifted Teacher. PMID- 26564942 TI - Readability and Understanding of Informed Consent Among Participants With Low Incomes: A Preliminary Report. AB - With passage and implementation of the Affordable Health Care Act, more vulnerable segments of the U.S. population will now have access to regular health care and increased opportunities to participate in biomedical research. Yet, access to new groups brings with it new responsibilities for investigators, most importantly, reducing burdens for participants. Data collected through this small pilot study suggest several preliminary but potentially important findings when working with adults from low-income populations: First, while all participants read some parts of the consent forms (55%), only a minority reported reading the entire form (45%); second, 73% of participants reported understanding the study very well whereas only 27% reported understanding the study "a little"; third, there was a slight reported advantage of the simplified form over the regular form; however, this difference varied by section. Relatedly, other research has shown a high incidence of persons reading none of the consent form, but signing a statement that they have read and understood the study. Why does this occur? What are we teaching people when we request that they sign a consent form they have chosen not to read? What are the ethical and regulatory implications? Embedded ethics studies such as this one, although pilot and preliminary in nature, offer a number of advantages, such as stimulating additional scientific inquiry as well as challenging established institutional practices. PMID- 26564943 TI - Investigator Experiences and Attitudes About Research With Biospecimens. AB - To advance scientific knowledge about human diseases and effective therapeutic treatments, investigators need access to human biospecimens and associated data. However, regulatory and procedural requirements may impede investigators' efforts to share biospecimens and data within and across institutions. Although a number of studies have explored experiences and attitudes of study participants and others about biospecimen and data sharing, less is known about investigators' perspectives. We conducted an electronic survey to learn about investigators' experiences and attitudes about research with biospecimens and associated data. A total of 114 practicing scientists from a pool of 60 university medical schools with Clinical and Translational Science Awards (CTSAs) funded by the National Institutes of Health (NIH) participated. We found a high degree of variability in investigators' experiences with institutional review boards (IRBs) when seeking approval to conduct biospecimen research, as well as differences in approaches to informed consent for the collection of specimens. Participants also expressed concerns that the risks of biospecimen research may be overestimated by IRBs. This research suggests that the current regulatory environment for human research protections may require reconsideration with regard to standards for collection, use, and sharing of biospecimens and data. PMID- 26564944 TI - The HIV and Drug Abuse Prevention Research Ethics Training Institute: Training Early-Career Scientists to Conduct Research on Research Ethics. AB - The responsible conduct of HIV/drug abuse prevention research requires investigators with both the knowledge of and ability to generate empirical data that can enhance global ethical practices and policies. This article describes a multidisciplinary program offering early-career professionals a 2-year intensive summer curriculum along with funding to conduct a mentored research study on a wide variety of HIV/drug abuse research ethics topics. Now in its fifth year, the program has admitted 29 trainees who have to date demonstrated increased knowledge of research ethics, produced 17 peer-reviewed publications, 46 professional presentations, and submitted or been awarded five related federal grants. The institute also hosts a global information platform providing general and HIV/drug abuse relevant research ethics educational and research resources that have had more than 38,800 unique visitors from more than 150 countries. PMID- 26564945 TI - The Impact of Institutional Review Boards (IRBs) on Clinical Innovation: A Survey of Investigators and IRB Members. AB - We conducted a survey to assess the perspectives of principal investigators and Institutional Review Board (IRB) members on the impact of the IRB structure on the conduct of research and innovative therapy, defined as a nonstandard treatment intended to enhance the well-being of an individual patient. Although investigators and IRB members agreed that the IRB provides adequate protection to study subjects (97% vs. 100%) and an ethically insightful review (88% vs. 100%), a third of clinical investigators felt that the IRB review process limits clinical innovation, in comparison with only 4% of IRB representatives. Limitations of the current IRB review process were explored. We propose several measures to improve the IRB review process while maintaining the protection of human research subjects, including the use of centralized IRBs, the opening of IRB meetings to investigators, the development of metrics and outcome measures for the IRB, and the promotion of guidelines that distinguish research and innovative therapy. PMID- 26564946 TI - Sham Surgery Research. PMID- 26564947 TI - On the Consequences of Purging and Linkage on Fitness and Genetic Diversity. AB - Using computer simulation we explore the consequences of linkage on the inbreeding load of an equilibrium population, and on the efficiency of purging and the loss of genetic diversity after a reduction in population size. We find that linkage tends to cause increased inbreeding load due to the build up of coupling groups of (partially) recessive deleterious alleles. It also induces associative overdominance at neutral sites but rarely causes increased neutral genetic diversity in equilibrium populations. After a reduction in population size, linkage can cause some delay both for the expression of the inbreeding load and the corresponding purging. However, reasonable predictions can be obtained for the evolution of fitness under inbreeding and purging by using empirical estimates of the inbreeding depression rate. Purging selection against homozygotes for deleterious alleles affects the population's pedigree. Furthermore, it can slow the loss of genetic diversity compared to that expected from the variance of gametic contributions to the breeding group and even from pedigree inbreeding. Under some conditions, this can lead to a smaller loss of genetic diversity, even below that expected from population size in the absence of selection. PMID- 26564948 TI - Comprehensive Transcriptome Analysis of Six Catfish Species from an Altitude Gradient Reveals Adaptive Evolution in Tibetan Fishes. AB - Glyptosternoid fishes (Siluriformes), one of the three broad fish lineages (the two other are schizothoracines and Triplophysa), have a limited distribution in the rivers in the Tibetan Plateau and peripheral regions. To investigate the genetic mechanisms underlying adaptation to the Tibetan Plateau in several fish species from gradient altitudes, a total of 20,659,183-37,166,756 sequence reads from six species of catfish were generated by Illumina sequencing, resulting in six assemblies. Analysis of the 1,656 orthologs among the six assembled catfish unigene sets provided consistent evidence for genome-wide accelerated evolution in the three glyptosternoid lineages living at high altitudes. A large number of genes refer to functional categories related to hypoxia and energy metabolism exhibited rapid evolution in the glyptosternoid lineages relative to yellowhead catfish living in plains areas. Genes showing signatures of rapid evolution and positive selection in the glyptosternoid lineages were also enriched in functions associated with energy metabolism and hypoxia. Our analyses provide novel insights into highland adaptation in fishes and can serve as a foundation for future studies aiming to identify candidate genes underlying the genetic basis of adaptation in Tibetan fishes. PMID- 26564949 TI - Genome-Wide Estimates of Mutation Rates and Spectrum in Schizosaccharomyces pombe Indicate CpG Sites are Highly Mutagenic Despite the Absence of DNA Methylation. AB - We accumulated mutations for 1952 generations in 79 initially identical, haploid lines of the fission yeast Schizosaccharomyces pombe, and then performed whole genome sequencing to determine the mutation rates and spectrum. We captured 696 spontaneous mutations across the 79 mutation accumulation (MA) lines. We compared the mutation spectrum and rate to a recently published equivalent experiment on the same species, and to another model ascomycetous yeast, the budding yeast Saccharomyces cerevisiae. While the two species are approximately 600 million years diverged from each other, they share similar life histories, genome size and genomic G/C content. We found that Sc. pombe and S. cerevisiae have similar mutation rates, but Sc. pombe exhibits a stronger insertion bias. Intriguingly, we observed an increased mutation rate at cytosine nucleotides, specifically CpG nucleotides, which is also seen in S. cerevisiae. However, the absence of methylation in Sc. pombe and the pattern of mutation at these sites, primarily C > A as opposed to C -> T, strongly suggest that the increased mutation rate is not caused by deamination of methylated cytosines. This result implies that the high mutability of CpG dinucleotides in other species may be caused in part by a methylation-independent mechanism. Many of our findings mirror those seen in the recent study, despite the use of different passaging conditions, indicating that MA is a reliable method for estimating mutation rates and spectra. PMID- 26564950 TI - Genomic Prediction Accounting for Residual Heteroskedasticity. AB - Whole-genome prediction (WGP) models that use single-nucleotide polymorphism marker information to predict genetic merit of animals and plants typically assume homogeneous residual variance. However, variability is often heterogeneous across agricultural production systems and may subsequently bias WGP-based inferences. This study extends classical WGP models based on normality, heavy tailed specifications and variable selection to explicitly account for environmentally-driven residual heteroskedasticity under a hierarchical Bayesian mixed-models framework. WGP models assuming homogeneous or heterogeneous residual variances were fitted to training data generated under simulation scenarios reflecting a gradient of increasing heteroskedasticity. Model fit was based on pseudo-Bayes factors and also on prediction accuracy of genomic breeding values computed on a validation data subset one generation removed from the simulated training dataset. Homogeneous vs. heterogeneous residual variance WGP models were also fitted to two quantitative traits, namely 45-min postmortem carcass temperature and loin muscle pH, recorded in a swine resource population dataset prescreened for high and mild residual heteroskedasticity, respectively. Fit of competing WGP models was compared using pseudo-Bayes factors. Predictive ability, defined as the correlation between predicted and observed phenotypes in validation sets of a five-fold cross-validation was also computed. Heteroskedastic error WGP models showed improved model fit and enhanced prediction accuracy compared to homoskedastic error WGP models although the magnitude of the improvement was small (less than two percentage points net gain in prediction accuracy). Nevertheless, accounting for residual heteroskedasticity did improve accuracy of selection, especially on individuals of extreme genetic merit. PMID- 26564951 TI - Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans. AB - Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC). Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5'-CpG-3' sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA. PMID- 26564953 TI - Conduction over and around the atrioventricular node: author's reply. PMID- 26564952 TI - Gene Expression and Chromatin Modifications Associated with Maize Centromeres. AB - Centromeres are defined by the presence of CENH3, a variant of histone H3. Centromeres in most plant species contain exclusively highly repetitive DNA sequences, which has hindered research on structure and function of centromeric chromatin. Several maize centromeres have been nearly completely sequenced, providing a sequence-based platform for genomic and epigenomic research of plant centromeres. Here we report a high resolution map of CENH3 nucleosomes in the maize genome. Although CENH3 nucleosomes are spaced ~190 bp on average, CENH3 nucleosomes that occupied CentC, a 156-bp centromeric satellite repeat, showed clear positioning aligning with CentC monomers. Maize centromeres contain alternating CENH3-enriched and CENH3-depleted subdomains, which account for 87% and 13% of the centromeres, respectively. A number of annotated genes were identified in the centromeres, including 11 active genes that were located exclusively in CENH3-depleted subdomains. The euchromatic histone modification marks, including H3K4me3, H3K36me3 and H3K9ac, detected in maize centromeres were associated mainly with the active genes. Interestingly, maize centromeres also have lower levels of the heterochromatin histone modification mark H3K27me2 relative to pericentromeric regions. We conclude that neither H3K27me2 nor the three euchromatic histone modifications are likely to serve as functionally important epigenetic marks of centromere identity in maize. PMID- 26564954 TI - Phrenic nerve injury during ablation with the second-generation cryoballoon: analysis of the temperature drop behaviour in a large cohort of patients. AB - AIMS: The present study sought to analyse the relationship between the temperature drop during the cryoenergy application and the occurrence of phrenic nerve injury (PNI) in a large cohort of patients having undergone second generation cryoballoon ablation (CB-A). METHODS AND RESULTS: The first 550 consecutive patients having undergone CB-A for atrial fibrillation were enrolled. Attained temperatures at 20, 30, 40, and 60 s during cryoablation in the right sided pulmonary veins (PVs) were collected. Diagnosis of PNI was made if reduced motility or paralysis of the hemidiaphragm was detected. The incidence of PNI in the study population was 7.3% (40/550); among them, only four (0.7%) did not resolve until discharge and one (0.2%) still persisted at 23 months. Patients with PNI exhibited significantly lower temperatures at 20, 30, and 40 s after the beginning of the cryoapplication in the right superior PV (RSPV) (P = 0.006, P = 0.003, and P = 0.003, respectively). The temperature drop expressed as Delta temperature/Delta time was also significantly higher in patients with PNI. Low temperature during the early phases of the freezing cycle (less than -38 degrees C at 40 s) predicted PNI with a sensitivity of 80.5%, a specificity of 77%, and a negative predictive value of 97.9%. Among patients with a fast temperature drop during RSPV ablation, an RSPV diameter >23.55 * 17.95 mm significantly predicted PNI occurrence. CONCLUSION: The analysis of the temperature course within the first 40 s after the initiation of the freezing cycle showed that the temperature dropped significantly faster in patients with PNI during ablation in the RSPV. PMID- 26564955 TI - Characterizing fast pathway in typical and atypical atrioventricular nodal re entrant tachycardia by atrial-His and His-atrial: more to consider. PMID- 26564956 TI - Nanoparticle-mediated rhodopsin cDNA but not intron-containing DNA delivery causes transgene silencing in a rhodopsin knockout model. AB - Previously, we compared the efficacy of nanoparticle (NP)-mediated intron containing rhodopsin (sgRho) vs. intronless cDNA in ameliorating retinal disease phenotypes in a rhodopsin knockout (RKO) mouse model of retinitis pigmentosa. We showed that NP-mediated sgRho delivery achieved long-term expression and phenotypic improvement in RKO mice, but not NP housing cDNA. However, the protein level of the NP-sgRho construct was only 5-10% of wild-type at 8 mo postinjection. To have a better understanding of the reduced levels of long-term expression of the vectors, in the present study, we evaluated the epigenetic changes of subretinal delivering NP-cDNA vs. NP-sgRho in the RKO mouse eyes. Following the administration, DNA methylation and histone status of specific regions (bacteria plasmid backbone, promoter, rhodopsin gene, and scaffold/matrix attachment region) of the vectors were evaluated at various time points. We documented that epigenetic transgene silencing occurred in vector-mediated gene transfer, which were caused by the plasmid backbone and the cDNA of the transgene, but not the intron-containing transgene. No toxicity or inflammation was found in the treated eyes. Our results suggest that cDNA of the rhodopsin transgene and bacteria backbone interfered with the host defense mechanism of DNA methylation-mediated transgene silencing through heterochromatin-associated modifications. PMID- 26564957 TI - Cyanobacterial community composition in Arctic soil crusts at different stages of development. AB - Cyanobacterial diversity in soil crusts has been extensively studied in arid lands of temperate regions, particularly semi-arid steppes and warm deserts. Nevertheless, Arctic soil crusts have received far less attention than their temperate counterparts. Here, we describe the cyanobacterial communities from various types of soil crusts from Svalbard, High Arctic. Four soil crusts at different development stages (ranging from poorly-developed to well-developed soil crusts) were analysed using 454 pyrosequencing of the V3-V4 variable region of the cyanobacterial 16S rRNA gene. Analyses of 95 660 cyanobacterial sequences revealed a dominance of OTUs belonging to the orders Synechococcales, Oscillatoriales and Nostocales. The most dominant OTUs in the four studied sites were related to the filamentous cyanobacteria Leptolyngbya sp. Phylotype richness estimates increased from poorly- to mid-developed soil crusts and decreased in the well-developed lichenized soil crust. Moreover, pH, ammonium and organic carbon concentrations appeared significantly correlated with the cyanobacterial community structure. PMID- 26564958 TI - Successive shifts in the microbial community of the surface mucus layer and tissues of the coral Acropora muricata under thermal stress. AB - The coral mucus may harbor commensal bacteria that inhibit growth of pathogens. Therefore, there is a need to understand the dynamics of bacterial communities between the coral mucus and tissues. Nubbins of Acropora muricata were subjected to increasing water temperatures of 26 degrees C-33 degrees C, to simultaneously explore the bacterial diversity in coral mucus and tissues by 16S rRNA gene amplicon sequencing. Photochemical efficiency of symbiotic dinoflagellates within the corals declined above 31 degrees C. Both the mucus and tissues of healthy A. muricata were dominated by gamma-Proteobacteria, but under thermal stress there was a shift towards bacteria from the Verrucomicrobiaceae and alpha Proteobacteria. Members of Cyanobacteria, Flavobacteria and Sphingobacteria also become more prominent at higher temperatures. The relative abundance of Vibrio spp. in the coral mucus increased at 29 degrees C, but at 31 degrees C, there was a drop in the relative abundance of Vibrio spp. in the mucus, with a reciprocal increase in the tissues. On the other hand, during bleaching, the relative abundance of Endozoicomonas spp. decreased in the tissues with a reciprocal increase in the mucus. This is the first systematic experiment that shows the potential for a bacterial community shift between the coral surface mucus and tissues in a thermally stressed coral. PMID- 26564959 TI - Cave microbial community composition in oceanic islands: disentangling the effect of different colored mats in diversity patterns of Azorean lava caves. AB - Processes determining diversity and composition of bacterial communities in island volcanic caves are still poorly understood. Here, we characterized colored microbial mats in 14 volcanic caves from two oceanic islands of the Azores using 16S rRNA gene sequences. Factors determining community diversity (alpha) and composition (beta) were explored, namely colored mats, caves and islands, as well as environmental and chemical characteristics of caves. Additive partitioning of diversity using OTU occurrence showed a greater influence of beta-diversity between islands and caves that may relate to differences in rare OTUs (singletons and doubletons) across scales. In contrast, Shannon diversity partitioning revealed the importance of the lowest hierarchical level (alpha diversity, colored mat), suggesting a dominance of cosmopolitan OTUs (>1%) in most samples. Cosmopolitan OTUs included members involved in nitrogen cycling, supporting the importance of this process in Azorean caves. Environmental and chemical conditions in caves did not show any significant relationship to OTU diversity and composition. The absence of clear differences between mat colors and across scales may be explained by (1) the geological youth of the cave system (cave communities have not had enough time to diverge) or/and (2) community convergence, as the result of selection pressure in extreme environments. PMID- 26564960 TI - Q-ing tumor glutaminase for therapy. PMID- 26564961 TI - Mitochondrial mass and DNA repair in breast cancer stem cells. PMID- 26564962 TI - Myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis is ameliorated in interleukin-32 alpha transgenic mice. AB - Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disease in which myelin in the spinal cord and brain are damaged. IL-32alpha is known as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory disease such as rheumatoid arthritis, chronic pulmonary disease, and cancers. However, the role of IL-32alpha on spinal cord injuries and demyelination is poorly understood. Recently, we reported that the release of proinflammatory cytokines were reduced in IL-32alpha-overexpressing transgenic mice. In this study, we investigated whether IL-32alpha plays a role on MS using experimental autoimmune encephalomyelitis (EAE), an experimental mouse model of MS, in human IL-32alpha Tg mice. The Tg mice were immunized with MOG35-55 suspended in CFA emulsion followed by pertussis toxin, and then EAE paralysis of mice was scored. We observed that the paralytic severity and neuropathology of EAE in IL-32alpha Tg mice were significantly decreased compared with that of non-Tg mice. The immune cells infiltration, astrocytes/microglials activation, and pro-inflammatory cytokines (IL-1beta and IL-6) levels in spinal cord were suppressed in IL-32alpha Tg mice. Furthermore, NG2 and O4 were decreased in IL-32alpha Tg mice, indicating that spinal cord damaging was suppressed. In addition, in vitro assay also revealed that IL-32alpha has a preventive role against Con A stimulation which is evidenced by decrease in T cell proliferation and inflammatory cytokine levels in IL-32alpha overexpressed Jurkat cell. Taken together, our findings suggested that IL-32alpha may play a protective role in EAE by suppressing neuroinflammation in spinal cord. PMID- 26564963 TI - Inflammasome effects in GvHD. PMID- 26564965 TI - Dissociation of cephamycin C and clavulanic acid biosynthesis by 1,3 diaminopropane in Streptomyces clavuligerus. AB - Streptomyces clavuligerus produces simultaneously cephamycin C (CephC) and clavulanic acid (CA). Adding 1,3-diaminopropane to culture medium stimulates production of beta-lactam antibiotics. However, there are no studies on the influence of this diamine on coordinated production of CephC and CA. This study indicates that 1,3-diaminopropane can dissociate CephC and CA productions. Results indicated that low diamine concentrations (below 1.25 g l(-1)) in culture medium increased CA production by 200%, but not that of CephC. Conversely, CephC production increased by 300% when 10 g l(-1) 1,3-diaminopropane was added to culture medium. Addition of just L-lysine (18.3 g l(-1)) to culture medium increased both biocompounds. On the other hand, while L-lysine plus 7.5 g l(-1) 1,3-diaminopropane increased volumetric production of CephC by 1100%, its impact on CA production was insignificant. The combined results suggest that extracellular concentration of 1,3-diaminopropane may trigger the dissociation of CephC and CA biosynthesis in S. clavuligerus. PMID- 26564964 TI - A comprehensive multiomics approach toward understanding the relationship between aging and dementia. AB - Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD. PMID- 26564966 TI - Detection of psychrophilic and psychrotolerant Clostridium spp. in chilled fresh vacuum-packed meat using different PCR methods. AB - Since 1989, blown pack spoilage has been recognized as a special form of spoilage in vacuum-packed raw and cooked beef. However, only limited information concerning the occurrences of bacteria causing blown pack spoilage on chilled fresh meat is available. In this study, a total of 63 beef and 33 lamb commercially available samples from different countries and without any signs of spoilage were examined for contamination with psychrophilic and psychrotolerant Clostridium spp. using different PCR systems. In total, 34.4% of the chilled fresh vacuum-packed meats were PCR positive. A higher number of lamb samples were identified as PCR positive compared with beef. A geographical relationship between positive results and the origin of the samples could not be determined. PCR system described by Brightwell and Clemens (Development and validation of a real-time PCR assay specific for Clostridium estertheticum and C. estertheticum like psychrotolerant bacteria. Meat Sci 2012;92:697-703) gave the highest number of positive detections compared with the Broda, Boerema and Bell PCR system (PCR detection of psychrophilic Clostridium spp. causing 'blown pack' spoilage of vacuum-packed chilled meats. J Appl Microbiol 2003;94:515-22). Eight clostridia isolates from two German beef and four Welsh lamb samples were isolated overall. Three of these clostridia isolates were identified as Clostridium estertheticum whereas five clostridia isolates remain unidentified. The study shows that psychrophilic and psychrotolerant Clostridium spp. are more prevalent in retail samples than previously suspected. PMID- 26564968 TI - Pulsar timing arrays: the promise of gravitational wave detection. AB - We describe the history, methods, tools, and challenges of using pulsars to detect gravitational waves. Pulsars act as celestial clocks detecting gravitational perturbations in space-time at wavelengths of light-years. The field is poised to make its first detection of nanohertz gravitational waves in the next 10 years. Controversies remain over how far we can reduce the noise in the pulsars, how many pulsars should be in the array, what kind of source we will detect first, and how we can best accommodate our large bandwidth systems. We conclude by considering the important question of how to plan for a post detection era, beyond the first detection of gravitational waves. PMID- 26564967 TI - Natural mummification of the human gut preserves bacteriophage DNA. AB - The natural mummification process of the human gut represents a unique opportunity to study the resulting microbial community structure and composition. While results are providing insights into the preservation of bacteria, fungi, pathogenic eukaryotes and eukaryotic viruses, no studies have demonstrated that the process of natural mummification also results in the preservation of bacteriophage DNA. We characterized the gut microbiome of three pre-Columbian Andean mummies, namely FI3, FI9 and FI12, and found sequences homologous to viruses. From the sequences attributable to viruses, 50.4% (mummy FI3), 1.0% (mummy FI9) and 84.4% (mummy FI12) were homologous to bacteriophages. Sequences corresponding to the Siphoviridae, Myoviridae, Podoviridae and Microviridae families were identified. Predicted putative bacterial hosts corresponded mainly to the Firmicutes and Proteobacteria, and included Bacillus, Staphylococcus, Clostridium, Escherichia, Vibrio, Klebsiella, Pseudomonas and Yersinia. Predicted functional categories associated with bacteriophages showed a representation of structural, replication, integration and entry and lysis genes. The present study suggests that the natural mummification of the human gut results in the preservation of bacteriophage DNA, representing an opportunity to elucidate the ancient phageome and to hypothesize possible mechanisms of preservation. PMID- 26564969 TI - Preface. PMID- 26564970 TI - pubmed.mineR: an R package with text-mining algorithms to analyse PubMed abstracts. AB - The PubMed literature database is a valuable source of information for scientific research. It is rich in biomedical literature with more than 24 million citations. Data-mining of voluminous literature is a challenging task. Although several text-mining algorithms have been developed in recent years with focus on data visualization, they have limitations such as speed, are rigid and are not available in the open source. We have developed an R package, pubmed.mineR, wherein we have combined the advantages of existing algorithms, overcome their limitations, and offer user flexibility and link with other packages in Bioconductor and the Comprehensive R Network (CRAN) in order to expand the user capabilities for executing multifaceted approaches. Three case studies are presented, namely, 'Evolving role of diabetes educators', 'Cancer risk assessment' and 'Dynamic concepts on disease and comorbidity' to illustrate the use of pubmed.mineR. The package generally runs fast with small elapsed times in regular workstations even on large corpus sizes and with compute intensive functions. The pubmed.mineR is available at http://cran.rproject. org/web/packages/pubmed.mineR. PMID- 26564971 TI - Analysis of core-periphery organization in protein contact networks reveals groups of structurally and functionally critical residues. AB - The representation of proteins as networks of interacting amino acids, referred to as protein contact networks (PCN), and their subsequent analyses using graph theoretic tools, can provide novel insights into the key functional roles of specific groups of residues. We have characterized the networks corresponding to the native states of 66 proteins (belonging to different families) in terms of their core-periphery organization. The resulting hierarchical classification of the amino acid constituents of a protein arranges the residues into successive layers - having higher core order - with increasing connection density, ranging from a sparsely linked periphery to a densely intra-connected core (distinct from the earlier concept of protein core defined in terms of the three-dimensional geometry of the native state, which has least solvent accessibility). Our results show that residues in the inner cores are more conserved than those at the periphery. Underlining the functional importance of the network core, we see that the receptor sites for known ligand molecules of most proteins occur in the innermost core. Furthermore, the association of residues with structural pockets and cavities in binding or active sites increases with the core order. From mutation sensitivity analysis, we show that the probability of deleterious or intolerant mutations also increases with the core order. We also show that stabilization centre residues are in the innermost cores, suggesting that the network core is critically important in maintaining the structural stability of the protein. A publicly available Web resource for performing core-periphery analysis of any protein whose native state is known has been made available by us at http://www.imsc.res.in/ ~sitabhra/proteinKcore/index.html. PMID- 26564972 TI - MIPCE: an MI-based protein complex extraction technique. AB - Protein-protein interaction (PPI) networks are believed to be important sources of information related to biological processes and complex metabolic functions of the cell. Identifying protein complexes is of great importance for understanding cellular organization and functions of organisms. In this work, a method is proposed, referred to as MIPCE, to find protein complexes in a PPI network based on mutual information.MIPCE has been biologically validated by GO-based score and satisfactory results have been obtained. We have also compared our method with some wellknown methods and obtained better results in terms of various parameters such as precession, recall and F-measure. PMID- 26564973 TI - DNA pattern recognition using canonical correlation algorithm. AB - We performed canonical correlation analysis as an unsupervised statistical tool to describe related views of the same semantic object for identifying patterns. A pattern recognition technique based on canonical correlation analysis (CCA) was proposed for finding required genetic code in the DNA sequence. Two related but different objects were considered: one was a particular pattern, and other was test DNA sequence. CCA found correlations between two observations of the same semantic pattern and test sequence. It is concluded that the relationship possesses maximum value in the position where the pattern exists. As a case study, the potential of CCA was demonstrated on the sequence found from HIV-1 preferred integration sites. The subsequences on the left and right flanking from the integration site were considered as the two views, and statistically significant relationships were established between these two views to elucidate the viral preference as an important factor for the correlation. PMID- 26564974 TI - Feature selection using feature dissimilarity measure and density-based clustering: application to biological data. AB - Reduction of dimensionality has emerged as a routine process in modelling complex biological systems. A large number of feature selection techniques have been reported in the literature to improve model performance in terms of accuracy and speed. In the present article an unsupervised feature selection technique is proposed, using maximum information compression index as the dissimilarity measure and the well-known density-based cluster identification technique DBSCAN for identifying the largest natural group of dissimilar features. The algorithm is fast and less sensitive to the user-supplied parameters. Moreover, the method automatically determines the required number of features and identifies them. We used the proposed method for reducing dimensionality of a number of benchmark data sets of varying sizes. Its performance was also extensively compared with some other well-known feature selection methods. PMID- 26564975 TI - Semi-supervised prediction of gene regulatory networks using machine learning algorithms. AB - Use of computational methods to predict gene regulatory networks (GRNs) from gene expression data is a challenging task. Many studies have been conducted using unsupervised methods to fulfill the task; however, such methods usually yield low prediction accuracies due to the lack of training data. In this article, we propose semi-supervised methods for GRN prediction by utilizing two machine learning algorithms, namely, support vector machines (SVM) and random forests (RF). The semi-supervised methods make use of unlabelled data for training. We investigated inductive and transductive learning approaches, both of which adopt an iterative procedure to obtain reliable negative training data from the unlabelled data. We then applied our semi-supervised methods to gene expression data of Escherichia coli and Saccharomyces cerevisiae, and evaluated the performance of our methods using the expression data. Our analysis indicated that the transductive learning approach outperformed the inductive learning approach for both organisms. However, there was no conclusive difference identified in the performance of SVM and RF. Experimental results also showed that the proposed semi-supervised methods performed better than existing supervised methods for both organisms. PMID- 26564976 TI - Identification of certain cancer-mediating genes using Gaussian fuzzy cluster validity index. AB - In this article, we have used an index, called Gaussian fuzzy index (GFI), recently developed by the authors, based on the notion of fuzzy set theory, for validating the clusters obtained by a clustering algorithm applied on cancer gene expression data. GFI is then used for the identification of genes that have altered quite significantly from normal state to carcinogenic state with respect to their mRNA expression patterns. The effectiveness of the methodology has been demonstrated on three gene expression cancer datasets dealing with human lung, colon and leukemia. The performance of GFI is compared with 19 exiting cluster validity indices. The results are appropriately validated biologically and statistically. In this context, we have used biochemical pathways, p-value statistics of GO attributes, t-test and zscore for the validation of the results. It has been reported that GFI is capable of identifying high-quality enriched clusters of genes, and thereby is able to select more cancer-mediating genes. PMID- 26564977 TI - Graph-based unsupervised feature selection and multiview clustering for microarray data. AB - A challenge in bioinformatics is to analyse volumes of gene expression data generated through microarray experiments and obtain useful information. Consequently, most microarray studies demand complex data analysis to infer biologically meaningful information from such high-throughput data. Selection of informative genes is an important data analysis step to identify a set of genes which can further help in finding the biological information embedded in microarray data, and thus assists in diagnosis, prognosis and treatment of the disease. In this article we present an unsupervised feature selection technique which attempts to address the goal of explorative data analysis, unfolding the multi-faceted nature of data. It focuses on extracting multiple clustering views considering the diversity of each view from high-dimensional data. We evaluated our technique on benchmark data sets and the experimental results indicates the potential and effectiveness of the proposed model in comparison to the traditional single view clustering models, as well as other existing methods used in the literature for the studied datasets. PMID- 26564979 TI - Knowledge-based analysis of functional impacts of mutations in microRNA seed regions. AB - MicroRNAs are a class of important post-transcriptional regulators. Genetic and somatic mutations in miRNAs, especially those in the seed regions, have profound and broad impacts on gene expression and physiological and pathological processes. Over 500 SNPs were mapped to the miRNA seeds, which are located at position 2-8 of the mature miRNA sequences. We found that the central positions of the miRNA seeds contain fewer genetic variants and therefore are more evolutionary conserved than the peripheral positions in the seeds. We developed a knowledgebased method to analyse the functional impacts of mutations in miRNA seed regions. We computed the gene ontology-based similarity score GOSS and the GOSS percentile score for all 517 SNPs in miRNA seeds. In addition to the annotation of SNPs for their functional effects, in the present article we also present a detailed analysis pipeline for finding the key functional changes for seed SNPs. We performed a detailed gene ontology graph-based analysis of enriched functional categories for miRNA target gene sets. In the analysis of a SNP in the seed region of hsa-miR-96 we found that two key biological processes for progressive hearing loss 'Neurotrophin TRK receptor signaling pathway' and 'Epidermal growth factor receptor signaling pathway' were significantly and differentially enriched by the two sets of allele-specific target genes of miRNA hsa-miR-96. PMID- 26564978 TI - Temporal protein expression pattern in intracellular signalling cascade during T cell activation: a computational study. AB - Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell's functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour. PMID- 26564980 TI - Phylogeny of metabolic networks: a spectral graph theoretical approach. AB - Many methods have been developed for finding the commonalities between different organisms in order to study their phylogeny. The structure of metabolic networks also reveals valuable insights into metabolic capacity of species as well as into the habitats where they have evolved. We constructed metabolic networks of 79 fully sequenced organisms and compared their architectures. We used spectral density of normalized Laplacian matrix for comparing the structure of networks. The eigenvalues of this matrix reflect not only the global architecture of a network but also the local topologies that are produced by different graph evolutionary processes like motif duplication or joining. A divergence measure on spectral densities is used to quantify the distances between various metabolic networks, and a split network is constructed to analyse the phylogeny from these distances. In our analysis, we focused on the species that belong to different classes, but appear more related to each other in the phylogeny. We tried to explore whether they have evolved under similar environmental conditions or have similar life histories. With this focus, we have obtained interesting insights into the phylogenetic commonality between different organisms. PMID- 26564981 TI - Protein-protein interaction site prediction in Homo sapiens and E. coli using an interaction-affinity based membership function in fuzzy SVM. AB - Protein-protein interaction (PPI) site prediction aids to ascertain the interface residues that participate in interaction processes. Fuzzy support vector machine (F-SVM) is proposed as an effective method to solve this problem, and we have shown that the performance of the classical SVM can be enhanced with the help of an interaction-affinity based fuzzy membership function. The performances of both SVM and F-SVM on the PPI databases of the Homo sapiens and E. coli organisms are evaluated and estimated the statistical significance of the developed method over classical SVM and other fuzzy membership-based SVM methods available in the literature. Our membership function uses the residue-level interaction affinity scores for each pair of positive and negative sequence fragments. The average AUC scores in the 10-fold cross-validation experiments are measured as 79.94% and 80.48% for the Homo sapiens and E. coli organisms respectively. On the independent test datasets, AUC scores are obtained as 76.59% and 80.17% respectively for the two organisms. In almost all cases, the developed F-SVM method improves the performances obtained by the corresponding classical SVM and the other classifiers, available in the literature. PMID- 26564982 TI - Flux balance analysis of genome-scale metabolic model of rice (Oryza sativa): aiming to increase biomass. AB - Due to socio-economic reasons, it is essential to design efficient stress tolerant, more nutritious, high yielding rice varieties. A systematic understanding of the rice cellular metabolism is essential for this purpose. Here, we analyse a genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential metabolic flexibility to increase the biosynthesis of any of the biomass components. We initially simulate the metabolic responses under an objective to maximize the biomass components. Using the estimated maximum value of biomass synthesis as a constraint, we further simulate the metabolic responses optimizing the cellular economy. Depending on the physiological conditions of a cell, the transport capacities of intracellular transporters (ICTs) can vary. To mimic this physiological state, we randomly vary the ICTs' transport capacities and investigate their effects. The results show that the rice leaf has the potential to increase glycine and starch in a wide range depending on the ICTs' transport capacities. The predicted biosynthesis pathways vary slightly at the two different optimization conditions. With the constraint of biomass composition, the cell also has the metabolic plasticity to fix a wide range of carbon-nitrogen ratio. PMID- 26564983 TI - Trehalose-6-phosphate synthase and stabilization of yeast glycolysis. PMID- 26564984 TI - Quantification of oxidative stress phenotypes based on high-throughput growth profiling of protein kinase and phosphatase knockouts. AB - Cellular responses to oxidative stress are important for restoring redox balance and ensuring cell survival. Genetic defects in response factors can lead to impaired response to oxidative damage and contribute to disease and aging. In single cell organisms, such as yeasts, the integrity of the oxidative stress response can be observed through its influences on growth characteristics. In this study, we investigated the time-dependent batch growth effects as a function of oxidative stress levels in protein kinase and phosphatase deletion backgrounds of Saccharomyces cerevisiae. In total, 41 different protein kinases and phosphatase mutants were selected for their known activities in oxidative stress or other stress response pathways and were investigated for their dosage dependent response to hydrogen peroxide. Detailed growth profiles were analyzed after the induction of stress for growth rate, lag time duration and growth efficiency, and by a novel method to identify stress-induced diauxic shift delay. This approach extracts more phenotypic information than traditional plate-based methods due to the assessment of time dynamics in the time scale of minutes. With this approach, we were able to identify surprisingly diverse sensitivity and resistance patterns as a function of gene knockout. PMID- 26564986 TI - The normativity of life scripts and its relation with life story events across cultures and subcultures. AB - This study explored the normativity of individual life scripts and their relation to actual life story memories across countries (Turkey and Germany) and subcultures (urban vs. rural, of migrant vs. of indigenous descent). Young adults from provincial Karabuk and metropolitan Istanbul (Turkey), second generation Turkish migrants and Germans from Frankfurt a.M. (Germany) provided both their individual versions of the life script and seven most important personal memories. We expected the agreement on the life script, that is, its normativity, and correspondingly its guiding influence on the selection of life story memories to correlate positively with a collectivistic, negatively an individualistic cultural orientation, that is, to be highest in provincial Karabuk, less in Istanbul, still less in Turkish migrants in Germany, and finally lowest in native Germans. The study confirmed expectations for the normativity of life scripts, but not for the normativity of most important memories. We conclude that the normativity of life scripts is influenced both by the individualist vs. collectivist orientation. PMID- 26564985 TI - Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration. AB - Age-related macular degeneration (AMD) is a common, blinding disease of the elderly in which macular photoreceptor cells, retinal pigment epithelium and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that degeneration of the choriocapillaris occurs early in this disease and that endothelial cell drop-out is concomitant with increased deposition of the complement membrane attack complex (MAC) at the choroidal endothelium. However, the impact of MAC injury to choroidal endothelial cells is poorly understood. To model this event in vitro, and to study the downstream consequences of MAC injury, endothelial cells were exposed to complement from human serum, compared to heat-inactivated serum, which lacks complement components. Cells exposed to complement components in human serum showed increased labelling with antibodies directed against the MAC, time- and dose-dependent cell death, as assessed by lactate dehydrogenase assay and increased permeability. RNA-Seq analysis following complement injury revealed increased expression of genes associated with angiogenesis including matrix metalloproteinase (MMP)-3 and -9, and VEGF-A. The MAC-induced increase in MMP9 RNA expression was validated using C5-depleted serum compared to C5-reconstituted serum. Increased levels of MMP9 were also established, using western blot and zymography. These data suggest that, in addition to cell lysis, complement attack on choroidal endothelial cells promotes an angiogenic phenotype in surviving cells. PMID- 26564987 TI - Study of the nucleation and growth of antibiotic labeled Au NPs and blue luminescent Au8 quantum clusters for Hg(2+) ion sensing, cellular imaging and antibacterial applications. AB - Herein, we report a detailed experimental study supported by DFT calculations to understand the mechanism behind the synthesis of cefradine (CFD--an antibiotic) labeled gold nanoparticles (Au NPs) by employing CFD as both a mild reducing and capping agent. The analysis of the effect of growth conditions reveals that a higher concentration of HAuCl4 results in the formation of an increasing fraction of anisotropic structures, higher temperature leads to the formation of quasi spherical particles instead of anisotropic ones, and larger pH leads to the formation of much smaller particles. The cyclic voltammetry (CV) results show that when the pH of the reaction medium increases from 4 to 6, the reduction potential of CFD increases which leads to the synthesis of nanoparticles (in a pH 4 reaction) to quantum clusters (in a pH 6 reaction). The MALDI-TOF mass spectrometry results of supernatant of the pH 6 reaction indicate the formation of [Au8(CFD)2S6] QCs which show fluorescence at ca. 432 nm with a Stokes shift of ca. 95 nm. The blue luminescence from Au8 QCs was applied for sensing of Hg(2+) ions on the basis of an aggregation-induced fluorescence quenching mechanism and offers good selectivity and a high sensitivity with a limit of detection ca. 2 nM which is lower than the detection requirement of 10 nM by the U.S. EPA and 30 nM by WHO for drinking water. We have also applied the sensing probe to detect Hg(2+) ions in bacterial samples. Further, we have investigated the antibacterial property of as-synthesized Au NPs using MIC, growth curve and cell survival assay. The results show that Au NPs could reduce the cell survival very efficiently rather than the cell growth in comparison to the antibiotic itself. The scanning electron microscopy study shows the degradation and blebbing of the bacterial cell wall upon exposure with Au NPs which was further supported by fluorescence microscopy results. These Au NPs did not show reactive oxygen species generation. We believe that the bacterial cytotoxicity is due to the direct contact of the Au NPs with bacterial cells. PMID- 26564988 TI - NUR77 exerts a protective effect against inflammatory bowel disease by negatively regulating the TRAF6/TLR-IL-1R signalling axis. AB - Nur77, an immediate-early response gene, participates in a wide range of biological functions. Its human homologue, NUR77, is known by several names and has the HGNC-approved gene symbol NR4A1. However, the role of Nur77 in inflammatory bowel disease (IBD) and its underlying mechanisms remain elusive. Here, using public data from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) on the most recent genome-wide association studies (GWAS) for ulcerative colitis (UC) and Crohn's disease (CD), we found that genetic variants of the NUR77 gene are associated with increased risk for both UC and CD. Accordingly, Nur77 expression was significantly reduced in colon tissues from patients with UC or CD and mice treated with DSS. Nur77 deficiency increased the susceptibility of mice to DSS-induced experimental colitis and prevented intestinal recovery, whereas treatment with cytosporone B (Csn-B), an agonist for Nur77, significantly attenuated excessive inflammatory response in the DSS induced colitis mouse model. Mechanistically, NUR77 acts as a negative regulator of TLR-IL-1R signalling by interacting with TRAF6. This interaction prevented auto-ubiquitination and oligomerization of TRAF6 and subsequently inhibited NF kappaB activation and pro-inflammatory cytokine production. Taken together, our GWAS-based analysis and in vitro and in vivo studies have demonstrated that Nur77 is an important regulator of TRAF6/TLR-IL-1R-initiated inflammatory signalling, and loss of Nur77 may contribute to the development of IBD, suggesting Nur77 as a potential target for the prevention and treatment of IBD. PMID- 26564989 TI - Male circumcision to prevent syphilis in 1855 and HIV in 1986 is supported by the accumulated scientific evidence to 2015: Response to Darby. AB - An article by Darby disparaging male circumcision (MC) for syphilis prevention in Victorian times (1837-1901) and voluntary medical MC programs for HIV prevention in recent times ignores contemporary scientific evidence. It is one-sided and cites outlier studies as well as claims by MC opponents that support the author's thesis, but ignores high quality randomised controlled trials and meta-analyses. While we agree with Darby that risky behaviours contribute to syphilis and HIV epidemics, there is now compelling evidence that MC helps reduce both syphilis and HIV infections. Although some motivations for MC in Victorian times were misguided, others, such as protection against syphilis, penile cancer, phimosis, balanitis and poor hygiene have stood the test of time. In the absence of a cure or effective prophylactic vaccine for HIV, MC should help lower heterosexually acquired HIV, especially when coupled with other interventions such as condoms and behaviour. This should save lives, as well as reducing costs and suffering. In contrast to Darby, our evaluation of the evidence leads us to conclude that MC would likely have helped reduce syphilis in Victorian times and, in the current era, will help lower both syphilis and HIV, so improving global public health. PMID- 26564990 TI - Novel MoSe2 hierarchical microspheres for applications in visible-light-driven advanced oxidation processes. AB - Advanced oxidation processes as a green technology have been adopted by combining the semiconductor catalyst MoSe2 with H2O2 under visible radiation. And novel three-dimensional self-assembled molybdenum diselenide (MoSe2) hierarchical microspheres from nanosheets were produced by using organic, selenium cyanoacetic acid sodium (NCSeCH2COONa) as the source of Se. The obtained products possess good crystallinity and present hierarchical structures with the average diameter of 1 MUm. The band gap of MoSe2 microspheres is 1.68 eV and they present excellent photocatalytic activity under visible light irradiation in the MoSe2 H2O2 system. This effective photocatalytic mechanism was investigated in this study and can be attributed to visible-light-driven advanced oxidation processes. PMID- 26564991 TI - Gingival crevicular fluid levels of protease-activated receptors type 1 and type 2 in diabetic patients with periodontitis. AB - BACKGROUND AND OBJECTIVE: Protease activated receptor type 1 (PAR1 ) seems to play a role in periodontal repair, while PAR2 is associated with periodontal inflammation. As diabetes is a known risk factor for periodontal disease, the aim of this study was to evaluate the influence of type 2 diabetes on PAR1 and PAR2 mRNA expression in the gingival crevicular fluid of patients with chronic periodontitis before and after non-surgical periodontal treatment. MATERIAL AND METHODS: Gingival crevicular fluid samples and clinical parameters consisting of measuring probing depth, clinical attachment level, bleeding on probing and plaque index were collected from systemically healthy patients and patients with type 2 diabetes and chronic periodontitis, at baseline and after non-surgical periodontal therapy. PAR1 and PAR2 , as well as the presence of the proteases RgpB gingipain and neutrophil proteinase-3 were assessed by quantitative polymerase chain reaction in the gingival crevicular fluid. RESULTS: The periodontal clinical parameters significantly improved after periodontal therapy (p < 0.01). Diabetes led to increased expression of PAR1 in gingival crevicular fluid, and in the presence of chronic periodontitis, it significantly decreased the expression of PAR1 and PAR2 (p < 0.05). Moreover, non-surgical periodontal treatment in diabetics resulted in increased expression of PAR1 and PAR2 (p < 0.05), and decreased expression of RgpB gingipain and proteinase-3 (p < 0.05). CONCLUSION: The present data demonstrated that diabetes was associated with an altered expression of PAR1 and PAR2 in the gingival crevicular fluid cells of subjects with chronic periodontitis. Future studies are necessary to elucidate the effects of PAR1 upregulation in periodontally healthy sites and PAR2 downregulation in chronic periodontitis sites on the increased susceptibility and severity of periodontitis in diabetes. PMID- 26564992 TI - Social support influences on eating awareness in children and adolescents: the mediating effect of self-regulatory strategies. AB - The impact of the social environment on healthy eating awareness results from complex interactions among physical, economic, cultural, interpersonal and individual characteristics. This study investigated the impact of social support and social influence on healthy eating awareness, controlling for socio-economic status, gender and age. Additionally, the mediating effect of self-regulation strategies was examined. A total of 2764 children and adolescents aged 10-17 from four European countries completed self-report measures on healthy eating awareness, social influence and the use of self-regulation strategies. Healthy eating awareness and the use of self-regulation strategies were more likely to occur among younger participants. An interaction between gender and age was related to the use of some self-regulation strategies; compared to girls, boys decreased the use of self-regulation strategies more from pre-adolescence to adolescence. Peer social influence was associated with more unhealthy eating in older participants. Results suggest a need to promote self-regulatory competences among young people in order to assist them with regulating their eating behaviours, especially in the presence of peers. Both school-based interventions and family-based interventions, focusing on self-regulation cognitions and social (peer) influence, could help children and adolescents to use self-regulatory strategies which are essential to eat healthier. PMID- 26564993 TI - Improving global health - is tourism's role in poverty elimination perpetuating poverty, powerlessness and 'ill-being'? AB - The spectrum of challenges for public health in a global context is ever expanding. It is difficult for health professionals to keep informed about details of key issues affecting global health determinants such as poverty. Tourism is seen as one strategy to eliminate poverty in developing countries and to improve global health, but the industry struggles with keeping its promise. Apart from often negative impacts on the well-being of local communities, it also turns out not to be as altruistic as it appears at first sight. Discourses largely focus on power and control of the non-poor over the poor despite all the rhetoric to the contrary. Economic aspects still dictate the debate rather than local people's understanding of well-being. Only with a major shift in the approach to local populations, acknowledging the communities' right to self determination and accepting them as equal partners with access to genuine benefits, will this disturbing imbalance be redressed and allow better health for more people possible. Public health professionals should question claims about the beneficial influence of tourism in poor regions and not lower their vigilance for poverty-related health problems, so that the poor are not overlooked when all other stakeholders are busy with their own agenda. PMID- 26564994 TI - Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica. AB - BACKGROUND: No large-scale studies have compared the efficacy of intravenous methylprednisolone pulse therapy (IVMP) for multiple sclerosis (MS) and neuromyelitis optica (NMO). OBJECTIVE: To explain differences in treatment responses of MS and NMO patients to IVMP. METHODS: Changes in neurological symptoms/signs and Expanded Disability Status Scale (EDSS) scores before and within 1 week of IVMP completion were obtained in 2010 at 28 institutions, and retrospectively collated from 271 MS (478 courses) and 73 NMO (118 courses) cases. RESULTS: In MS patients, decreased EDSS score was significant after the first (-0.8 +/- 0.9), second (-0.7 +/- 0.9), and third (-0.7 +/- 0.8) courses (p < 0.05), but not after the fourth (-0.3 +/- 0.7) and fifth (-0.5 +/- 0.6). However, decreased EDSS score was only significant after the first course (-0.5 +/- 1.5, p < 0.05) in NMO patients. EDSS score was significantly decreased in MS compared with NMO patients at the first course (p < 0.05), but not thereafter. Model analysis for EDSS score improvement at the first course, adjusting for covariates, showed significantly greater decreases in MS compared with NMO patients (p < 0.05). CONCLUSION: IVMP is effective in MS from the first to third courses, and in NMO at the first course. Additionally, IVMP is more efficacious in MS than NMO patients, even at the first course. PMID- 26564995 TI - Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients. AB - BACKGROUND: In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML). OBJECTIVE: To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability. METHODS: In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions (n = 21) or new MS lesions (n = 20) or no new lesions (n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated. RESULTS: Overall sensitivity and specificity for the detection of new lesions, regardless of the nature of the lesions, were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate. CONCLUSION: The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate. PMID- 26564996 TI - Interferon beta-1a long-term therapy related to pulmonary arterial hypertension in multiple sclerosis patients. AB - We report two patients with relapsing remitting multiple sclerosis (RRMS) on interferon (IFN) beta-1a treatment for more than 7 years who developed pulmonary arterial hypertension (PAH). Patient 1 developed severe PAH requiring lung transplantation. Histology showed typical proliferative lesions including plexiform lesions consistent with PAH. Patient 2 ceased IFN beta-1a, and their symptoms stabilised. Both cases highlight IFN beta-1a treatment as a potential risk factor for PAH. PAH needs to be considered as a diagnosis in patients on long-term IFN beta-1a treatment who develop new-onset respiratory symptoms. PMID- 26564997 TI - High-resolution T1-relaxation time mapping displays subtle, clinically relevant, gray matter damage in long-standing multiple sclerosis. AB - BACKGROUND: Gray matter (GM) pathology has high clinical relevance in multiple sclerosis (MS), but conventional magnetic resonance imaging (MRI) is insufficiently sensitive to visualize the rather subtle damage. OBJECTIVE: To investigate whether high spatial resolution T1-relaxation time (T1-RT) measurements can detect changes in the normal-appearing GM of patients with long standing MS and whether these changes are associated with physical and cognitive impairment. METHODS: High spatial resolution (1.05 * 1.05 * 1.2 mm(3)) T1-RT measurements were performed at 3 T in 156 long-standing MS patients and 54 healthy controls. T1-RT histogram parameters in several regions were analyzed to investigate group differences. Stepwise linear regression analyses were used to assess the relation of T1-RT with physical and cognitive impairment. RESULTS: In both thalamus and cortex, T1-RT histogram skewness was higher in patients than controls. In the cortex, this was driven by the frontal and temporal lobes. No differences were found in other GM histogram parameters. Cortical skewness, thalamus volume, and average white matter (WM) lesion T1-RT emerged as the strongest predictors for cognitive performance (adjusted R(2) = 0.39). CONCLUSION: Subtle GM damage was present in the cortex and thalamus of MS patients, as indicated by increased T1-RT skewness. Increased cortical skewness emerged as an independent predictor of cognitive dysfunction. PMID- 26564998 TI - A comparative analysis of Patient-Reported Expanded Disability Status Scale tools. AB - BACKGROUND: Patient-Reported Expanded Disability Status Scale (PREDSS) tools are an attractive alternative to the Expanded Disability Status Scale (EDSS) during long term or geographically challenging studies, or in pressured clinical service environments. OBJECTIVES: Because the studies reporting these tools have used different metrics to compare the PREDSS and EDSS, we undertook an individual patient data level analysis of all available tools. METHODS: Spearman's rho and the Bland-Altman method were used to assess correlation and agreement respectively. RESULTS: A systematic search for validated PREDSS tools covering the full EDSS range identified eight such tools. Individual patient data were available for five PREDSS tools. Excellent correlation was observed between EDSS and PREDSS with all tools. A higher level of agreement was observed with increasing levels of disability. In all tools, the 95% limits of agreement were greater than the minimum EDSS difference considered to be clinically significant. However, the intra-class coefficient was greater than that reported for EDSS raters of mixed seniority. The visual functional system was identified as the most significant predictor of the PREDSS-EDSS difference. CONCLUSION: This analysis will (1) enable researchers and service providers to make an informed choice of PREDSS tool, depending on their individual requirements, and (2) facilitate improvement of current PREDSS tools. PMID- 26564999 TI - Imaging Predictors of Improvement From a Motor Learning-Based Intervention for Children With Unilateral Cerebral Palsy. AB - Background Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children's Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results Improvements were seen across assessments; AHA (P = 0.04), JTTHF (P < .001) and CHEQ (P < 0.001). Radiological score significantly correlated with improvement at T2; AHA (r = .475) and CHEQ (r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = -.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = -.562, T3: r = -0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 (r = -547) and AHA at T3 (r = -.656). Conclusions Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP. PMID- 26565000 TI - Apelin targets gut contraction to control glucose metabolism via the brain. AB - OBJECTIVE: The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. DESIGN: We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. RESULTS: In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. CONCLUSIONS: Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. PMID- 26565001 TI - Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT. AB - Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil >=0.5*10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia free survival than bone marrow grafts. However, there is an increase in chronic graft-versus-host disease after peripheral blood grafts. Long-term follow up is needed to clarify whether chronic graft-versus-host disease might increase the risk of late morbidity and mortality. PMID- 26565002 TI - Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia. AB - In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl 2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. PMID- 26565003 TI - Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection. AB - BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. METHODS: We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. RESULTS: One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 * 10(6) (6 * 10(10)) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 * 10(4) copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. CONCLUSIONS: The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection. PMID- 26565004 TI - Illness Severity and Work Productivity Loss Among Working Adults With Medically Attended Acute Respiratory Illnesses: US Influenza Vaccine Effectiveness Network 2012-2013. AB - BACKGROUND: Influenza causes significant morbidity and mortality, with considerable economic costs, including lost work productivity. Influenza vaccines may reduce the economic burden through primary prevention of influenza and reduction in illness severity. METHODS: We examined illness severity and work productivity loss among working adults with medically attended acute respiratory illnesses and compared outcomes for subjects with and without laboratory confirmed influenza and by influenza vaccination status among subjects with influenza during the 2012-2013 influenza season. RESULTS: Illnesses laboratory confirmed as influenza (ie, cases) were subjectively assessed as more severe than illnesses not caused by influenza (ie, noncases) based on multiple measures, including current health status at study enrollment (<=7 days from illness onset) and current activity and sleep quality status relative to usual. Influenza cases reported missing 45% more work hours (20.5 vs 15.0; P < .001) than noncases and subjectively assessed their work productivity as impeded to a greater degree (6.0 vs 5.4; P < .001). Current health status and current activity relative to usual were subjectively assessed as modestly but significantly better for vaccinated cases compared with unvaccinated cases; however, no significant modifications of sleep quality, missed work hours, or work productivity loss were noted for vaccinated subjects. CONCLUSIONS: Influenza illnesses were more severe and resulted in more missed work hours and productivity loss than illnesses not confirmed as influenza. Modest reductions in illness severity for vaccinated cases were observed. These findings highlight the burden of influenza illnesses and illustrate the importance of laboratory confirmation of influenza outcomes in evaluations of vaccine effectiveness. PMID- 26565005 TI - Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double Blind, Placebo-Controlled Trial. AB - BACKGROUND: Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. METHODS: Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. RESULTS: Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. CONCLUSIONS: We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.Chinese Clinical Trials Registration. ISRCTN03147572. PMID- 26565006 TI - Editorial Commentary: Cryptococcosis in AIDS: New Data but Questions Remain. PMID- 26565007 TI - Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study. AB - BACKGROUND: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited. METHODS: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts <=100 cells/uL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year. RESULTS: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients. CONCLUSIONS: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease. PMID- 26565008 TI - Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study. AB - BACKGROUND: Managing recurrent Clostridium difficile infection (CDI) presents a significant challenge for clinicians and patients. Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent CDI, yet availability of a standardized, safe, and effective product has been lacking. Our aim in this study was to assess the safety and effectiveness of RBX2660 (microbiota suspension), a commercially prepared FMT drug manufactured using standardized processes and available in a ready-to-use format. METHODS: Patients with at least 2 recurrent CDI episodes or at least 2 severe episodes resulting in hospitalization were enrolled in a prospective, multicenter open-label study of RBX2660 administered via enema. Intensive surveillance for adverse events (AEs) was conducted daily for 7 days following treatment and then at 30 days, 60 days, 3 months, and 6 months. The primary objective was product-related AEs. A secondary objective was CDI-associated diarrhea resolution at 8 weeks. RESULTS: Of the 40 patients enrolled at 11 centers in the United States between 15 August 2013 and 16 December 2013, 34 received at least 1 dose of RBX2660 and 31 completed 6-month follow-up. Overall efficacy was 87.1% (16 with 1 dose and 11 with 2 doses). Of 188 reported AEs, diarrhea, flatulence, abdominal pain/cramping, and constipation were most common. The frequency and severity of AEs decreased over time. Twenty serious AEs were reported in 7 patients; none were related to RBX2660 or its administration. CONCLUSIONS: Among patients with recurrent or severe CDI, administration of RBX2660 via enema appears to be safe and effective. CLINICAL TRIALS REGISTRATION: NCT01925417. PMID- 26565009 TI - Editorial Commentary: Chronic Lung Allograft Dysfunction in Lung Transplant Recipients: Another Piece of the Puzzle. PMID- 26565010 TI - Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction. AB - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). METHODS: We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. RESULTS: Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2-3.9), P = .01 and 1.9 (1.1-3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9-11.6), P < .01; 3.4 (1.5-7.5), P < .01; and 2.4 (1.2 5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. CONCLUSIONS: Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted. PMID- 26565011 TI - Everywhere in Japan: an international approach to working with commercial gay businesses in HIV prevention. AB - In the UK and Japan, there is concern regarding rising rates of annual new HIV infections among Men who have Sex with Men (MSM). Whilst in the UK and Europe, gay businesses are increasingly recognized as being important settings through which to deliver HIV prevention and health promotion interventions to target vulnerable populations; in Japan such settings-based approaches are relatively underdeveloped. This article draws on qualitative data from a recently completed study conducted to explore whether it is feasible, acceptable and desirable to build on the recent European Everywhere project for adaptation and implementation in Japan. A series of expert workshops were conducted in Tokyo, Nagoya and Osaka with intersectoral representatives from Japanese and UK non-governmental organizations (NGOs), gay businesses, universities and gay communities (n = 46). Further discussion groups and meetings were held with NGO members and researchers from the Japanese Ministry of Health, Labour and Welfare's Research Group on HIV Prevention Policy, Programme Implementation and Evaluation among MSM (n = 34). The results showed that it is desirable, feasible and acceptable to adapt and implement a Japanese version of Everywhere. Such a practical, policy-relevant, settings-based HIV prevention framework for gay businesses may help to facilitate the necessary scale up of prevention responses among MSM in Japan. Given the high degree of sexual mobility between countries in Asia, there is considerable potential for the Everywhere Project (or its Japanese variant) to be expanded and adapted to other countries within the Asia-Pacific region. PMID- 26565012 TI - Novel Imaging Approaches for Predicting Arrhythmic Risk. AB - Determination of ventricular arrhythmic risk is crucial for guiding management of cardiac disease. Although for patients at increased risk an implantable cardioverter-defibrillator is recommended, it is widely acknowledged that current criteria for device use based predominantly on left ventricular ejection fraction are deficient. Genesis of ventricular arrhythmias involves a complex interaction of myocardial substrate abnormalities, precipitating triggers, and modulating factors. There are much data showing that by more directly assessing these factors, noninvasive imaging using echocardiography, radionuclide imaging, and cardiac magnetic resonance enhances arrhythmic risk stratification beyond ejection fraction and commonly used electrocardiographic and serum biomarkers. It is anticipated that further technological advancements studied in well-designed clinical trials will provide both more precise determination of risk and guide therapies to enhanced survival and patient well-being. PMID- 26565015 TI - When sepsis persists: a review of MRSA bacteraemia salvage therapy. AB - MRSA bacteraemia (MRSAB), including infective endocarditis, carries a high mortality rate, with up to 50% of patients failing initial therapy with vancomycin and requiring salvage therapy. Persistent MRSAB can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteraemia still persists despite surgical intervention. Although vancomycin and daptomycin are the only two antibiotics approved by the US FDA for the treatment of patients with MRSAB as monotherapy, the employment of novel strategies is required to effectively treat patients with persistent MRSAB and these may frequently involve combination drug therapy. Treatment strategies that are reviewed in this manuscript include vancomycin combined with a beta-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy and fosfomycin-based therapy. We recommend that combination antibiotic therapy be considered for use in MRSAB salvage treatment. PMID- 26565013 TI - Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials. AB - RATIONALE: Assessing the underlying ionic currents during a triggered action potential (AP) in intact perfused hearts offers the opportunity to link molecular mechanisms with pathophysiological problems in cardiovascular research. The developed loose patch photolysis technique can provide striking new insights into cardiac function at the whole heart level during health and disease. OBJECTIVE: To measure transmembrane ionic currents during an AP to determine how and when surface Ca(2+) influx that triggers Ca(2+)-induced Ca(2+) release occurs and how Ca(2+)-activated conductances can contribute to the genesis of AP phase 2. METHODS AND RESULTS: Loose patch photolysis allows the measurement of transmembrane ionic currents in intact hearts. During a triggered AP, a voltage dependent Ca(2+) conductance was fractionally activated (dis-inhibited) by rapidly photo-degrading nifedipine, the Ca(2+) channel blocker. The ionic currents during a mouse ventricular AP showed a fast early component and a slower late component. Pharmacological studies established that the molecular basis underlying the early component was driven by an influx of Ca(2+) through the L type channel, CaV 1.2. The late component was identified as an Na(+)-Ca(2+) exchanger current mediated by Ca(2+) released from the sarcoplasmic reticulum. CONCLUSIONS: The novel loose patch photolysis technique allowed the dissection of transmembrane ionic currents in the intact heart. We were able to determine that during an AP, L-type Ca(2+) current contributes to phase 1, whereas Na(+)-Ca(2+) exchanger contributes to phase 2. In addition, loose patch photolysis revealed that the influx of Ca(2+) through L-type Ca(2+) channels terminates because of voltage-dependent deactivation and not by Ca(2+)-dependent inactivation, as commonly believed. PMID- 26565016 TI - Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients. AB - OBJECTIVES: Hidradenitis suppurativa (HS) is an inflammatory skin disease typically localized in the axillae and inguinal and perineal areas. In the absence of standardized medical treatment, severe HS patients present chronic suppurative lesions with polymicrobial anaerobic abscesses. Wide surgery is the cornerstone treatment of severe HS, but surgical indications are limited by the extent of lesions. Intravenous broad-spectrum antibiotics may help control HS, but their efficacy is not documented. This study was designed to assess the efficacy of a 6 week course of ertapenem (1 g daily) and of antibiotic consolidation treatments for 6 months (M6) in severe HS. PATIENTS AND METHODS: Thirty consecutive patients with severe HS were retrospectively included in this study. The clinical severity of HS was assessed using the Sartorius score, which takes into account the number and severity of lesions. RESULTS: The median (IQR) Sartorius score dropped from 49.5 (28-62) at baseline to 19.0 (12-28) after ertapenem (P < 10(-4)). Five patients were lost to follow-up thereafter. At M6 the Sartorius score further decreased for the 16 patients who received continuous consolidation treatments, since 59% of HS areas reached clinical remission at M6 (i.e. absence of any inflammatory symptoms, P < 10(-4)). Nine patients interrupted or received intermittent consolidation treatments due to poor observance or irregular follow-up. Their Sartorius score stopped improving or returned to baseline. No major adverse event occurred. CONCLUSIONS: Ertapenem can dramatically improve severe HS. Consolidation treatments are needed to further improve HS and are mandatory to prevent relapses. Combined with surgery, optimized antibiotic treatments may be promising in severe HS. PMID- 26565017 TI - Effect of experimental modulation of mood on perception of exertional dyspnea in healthy subjects. AB - In many diseases across a range of pathologies (e.g., cardiopulmonary, neuromuscular, and cancer), chronic dyspnea, particularly on exertion, is a major debilitating symptom often associated with clinical anxiety/depression. This study aims to explore the interaction between mood state and exertional dyspnea in a healthy population. Following familiarization, 20 healthy subjects (27-54 years old) performed six 5-min treadmill tests on three separate days. On each day subjects viewed randomly assigned images designed to induce positive, negative, or neutral mood states (International Affective Picture System). For each condition, at minute intervals, subjects rated dyspnea (sensory and affective domains) in the first test and mood (valence and arousal domains) in the second test. Oxygen uptake (VO2 , liters/min), carbon dioxide production (VCO2, liters/min), ventilation (VE, liters/min), respiratory frequency (f(R), beats/min), and heart rate (HR, bpm), were measured throughout the exercise. VO2, VCO2, VE, HR, and f(R) were not statistically significantly different among the three mood states (P > 0.05). Mood valence was significantly higher with parallel viewing of positive (last 2-min mean +/- SE = 6.9 +/- 0.2) compared with negative pictures (2.4 +/- 0.2; P < 0.001). Both sensory and affective domains of dyspnea were significantly higher during negative (sensory: 5.6 +/- 0.3; affective: 3.3 +/- 0.5) compared with positive mood (sensory: 4.4 +/- 0.4, P < 0.001; affective: 2.1 +/- 0.4, P = 0.002). These findings suggest that positive mood alleviates both the sensory and affective domains of exertional dyspnea in healthy subjects. Thus the treatment of anxiety/depression in dyspenic populations could be a worthwhile therapeutic strategy in increasing symptom-limited exercise tolerance, thereby contributing to improved quality of life. PMID- 26565018 TI - Constructing quasi-linear VO2 responses from nonlinear parameters. AB - Oxygen uptake (VO2) kinetics have been shown to be governed by a nonlinear control system across a range of work rates. However, the linearity of the VO2 response to ramp incremental exercise would appear to be the result of a linear control system. This apparent contradiction could represent a balancing of changing VO2 kinetics parameter values across a range of work rates. To test this, six healthy men completed bouts of ramp incremental exercise at 15, 30, and 60 W/min (15R, 30R, 60R, respectively) and four bouts of an extended-step incremental exercise. VO2 parameter values were derived from the step exercise using two monoexponential models: one starting at time zero and encompassing the entire stage (MONO), and the other truncated to the first 5 min and allowing a time delay (5TD). The resulting parameter values were applied to an integrative model to estimate the ramp responses. As work rate increased, gain values increased (P < 0.001 for MONO and 5TD), as did mean response time (or time constant) values (MONO: P < 0.001; 5TD: P = 0.003). Up to maximal VO2 (VO(2 max)), the gains of the estimated ramp responses from both models were not different from the gains of the actual observed VO2 responses for 15R and 30R (15R: 11.3 +/- 1.2, 11.7 +/- 0.7, 10.9 +/- 0.3; 30R: 10.5 +/- 0.8, 11.0 +/- 0.5, 10.7 +/- 0.3 ml O2.min(-1).W(-1), for actual, MONO, 5TD, respectively) but were significantly greater for 60R (8.7 +/- 1.0, 9.9 +/- 0.4, 10.3 +/- 0.3 ml O2.min( 1).W(-1) for actual, MONO, 5TD, respectively). Up to 80%VO(2 max) gain values were not significantly different for any ramp rate (P > 0.05 for all). We conclude that the apparent linearity of the VO2 response to ramp incremental exercise is consequent to a balancing of increasing time constant and gain parameter values. PMID- 26565019 TI - No reserve in isokinetic cycling power at intolerance during ramp incremental exercise in endurance-trained men. AB - During whole body exercise in health, maximal oxygen uptake (Vo2max) is typically attained at or immediately before the limit of tolerance (LoT). At the Vo2max and LoT of incremental exercise, a fundamental, but unresolved, question is whether maximal evocable power can be increased above the task requirement, i.e., whether there is a "power reserve" at the LoT. Using an instantaneous switch from cadence independent (hyperbolic) to isokinetic cycle ergometry, we determined maximal evocable power at the limit of ramp-incremental exercise. We hypothesized that in endurance-trained men at LoT, maximal (4 s) isokinetic power would not differ from the power required by the task. Baseline isokinetic power at 80 rpm (Piso; measured at the pedals) and summed integrated EMG from five leg muscles (SigmaiEMG) were measured in 12 endurance-trained men (Vo2max = 4.2 +/- 1.0 l/min). Participants then completed a ramp incremental exercise test (20-25 W/min), with instantaneous measurement of Piso and SigmaiEMG at the LoT. Piso decreased from 788 +/- 103 W at baseline to 391 +/- 72 W at LoT, which was not different from the required ramp-incremental flywheel power (352 +/- 58 W; P > 0.05). At LoT, the relative reduction in Piso was greater than the relative reduction in the isokinetic SigmaiEMG (50 +/- 9 vs. 63 +/- 10% of baseline; P < 0.05). During maximal ramp incremental exercise in endurance-trained men, maximum voluntary power is not different from the power required by the task and is consequent to both central and peripheral limitations in evocable power. The absence of a power reserve suggests both the perceptual and physiological limits of maximum voluntary power production are not widely dissociated at LoT in this population. PMID- 26565020 TI - The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose). AB - Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNA-damage responses through its N terminal region in a poly(ADP-ribose) polymerase-dependent manner. We have identified and determined the structure of a stable domain (CHD4-N) in this N terminal region. The-fold consists of a four-alpha-helix bundle with structural similarity to the high mobility group box, a domain that is well known as a DNA binding module. We show that the CHD4-N domain binds with higher affinity to poly(ADP-ribose) than to DNA. We also show that the N-terminal region of CHD4, although not CHD4-N alone, is essential for full nucleosome remodeling activity and is important for localizing CHD4 to sites of DNA damage. Overall, these data build on our understanding of how CHD4-NuRD acts to regulate gene expression and participates in the DNA-damage response. PMID- 26565021 TI - A Cytosolic Multiprotein Complex Containing p85alpha Is Required for beta-Catenin Activation in Colitis and Colitis-associated Cancer. AB - Wnt/beta-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated beta-catenin (pbeta-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in beta-catenin signaling in the intestine. The MCC contains p85alpha, the class IA subunit of PI3K, along with beta-catenin, 14-3 3zeta, Akt, and p110alpha. MCC levels in IEC increase in colitis and colitis associated cancer patients. IEC-specific p85alpha-deficient (p85(DeltaIEC)) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial beta-catenin activation. In colonic IEC, p85alpha deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces beta-catenin signaling. Despite worse colitis, p85(DeltaIEC) mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the beta-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients. PMID- 26565022 TI - Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10 induced ERK1/2 Phosphorylation. AB - Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18alpha-glycyrrhetinic acid (18alpha-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43( /-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18alpha-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18alpha-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. PMID- 26565023 TI - Contributions of the Prion Protein Sequence, Strain, and Environment to the Species Barrier. AB - Amyloid propagation requires high levels of sequence specificity so that only molecules with very high sequence identity can form cross-beta-sheet structures of sufficient stringency for incorporation into the amyloid fibril. This sequence specificity presents a barrier to the transmission of prions between two species with divergent sequences, termed a species barrier. Here we study the relative effects of protein sequence, seed conformation, and environment on the species barrier strength and specificity for the yeast prion protein Sup35p from three closely related species of the Saccharomyces sensu stricto group; namely, Saccharomyces cerevisiae, Saccharomyces bayanus, and Saccharomyces paradoxus. Through in vivo plasmid shuffle experiments, we show that the major characteristics of the transmission barrier and conformational fidelity are determined by the protein sequence rather than by the cellular environment. In vitro data confirm that the kinetics and structural preferences of aggregation of the S. paradoxus and S. bayanus proteins are influenced by anions in accordance with their positions in the Hofmeister series, as observed previously for S. cerevisiae. However, the specificity of the species barrier is primarily affected by the sequence and the type of anion present during the formation of the initial seed, whereas anions present during the seeded aggregation process typically influence kinetics rather than the specificity of prion conversion. Therefore, our work shows that the protein sequence and the conformation variant (strain) of the prion seed are the primary determinants of cross-species prion specificity both in vivo and in vitro. PMID- 26565024 TI - Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide induced Neuroinflammation. AB - Monoglyceride lipase (MGL) is required for efficient hydrolysis of the endocannabinoid 2-arachidonoylglyerol (2-AG) in the brain generating arachidonic acid (AA) and glycerol. This metabolic function makes MGL an interesting target for the treatment of neuroinflammation, since 2-AG exhibits anti-inflammatory properties and AA is a precursor for pro-inflammatory prostaglandins. Astrocytes are an important source of AA and 2-AG, and highly express MGL. In the present study, we dissected the distinct contribution of MGL in astrocytes on brain 2-AG and AA metabolism by generating a mouse model with genetic deletion of MGL specifically in astrocytes (MKO(GFAP)). MKO(GFAP) mice exhibit moderately increased 2-AG and reduced AA levels in brain. Minor accumulation of 2-AG in the brain of MKO(GFAP) mice does not cause cannabinoid receptor desensitization as previously observed in mice globally lacking MGL. Importantly, MKO(GFAP) mice exhibit reduced brain prostaglandin E2 and pro-inflammatory cytokine levels upon peripheral lipopolysaccharide (LPS) administration. These observations indicate that MGL-mediated degradation of 2-AG in astrocytes provides AA for prostaglandin synthesis promoting LPS-induced neuroinflammation. The beneficial effect of astrocyte-specific MGL-deficiency is not fully abrogated by the inverse cannabinoid receptor 1 agonist SR141716 (Rimonabant) suggesting that the anti inflammatory effects are rather caused by reduced prostaglandin synthesis than by activation of cannabinoid receptors. In conclusion, our data demonstrate that MGL in astrocytes is an important regulator of 2-AG levels, AA availability, and neuroinflammation. PMID- 26565025 TI - Transforming Growth Factor beta1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1 NADPH Oxidase 4 Axis. AB - TGF-beta is a pleiotropic cytokine that accumulates during kidney injuries, resulting in various renal diseases. We have reported previously that TGF-beta1 induces the selective up-regulation of mitochondrial Nox4, playing critical roles in podocyte apoptosis. Here we investigated the regulatory mechanism of Nox4 up regulation by mTORC1 activation on TGF-beta1-induced apoptosis in immortalized podocytes. TGF-beta1 treatment markedly increased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4EBP1. Blocking TGF-beta receptor I with SB431542 completely blunted the phosphorylation of mTOR, p70S6K, and 4EBP1. Transient adenoviral overexpression of mTOR-WT and constitutively active mTORDelta augmented TGF-beta1-treated Nox4 expression, reactive oxygen species (ROS) generation, and apoptosis, whereas mTOR kinase-dead suppressed the above changes. In addition, knockdown of mTOR mimicked the effect of mTOR-KD. Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-beta1. Pharmacological inhibition of the MEK-ERK cascade, but not the PI3K-Akt-TSC2 pathway, abolished TGF-beta1 induced mTOR activation. Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-beta1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-beta1. Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF beta1-induced ERK1/2-mTORactivation. Our data suggest that TGF-beta1 increases translation of Nox4 through the Smad-ERK1/2-mTORC1 axis, which is independent of transcriptional regulation. Activation of this pathway plays a crucial role in ROS generation and mitochondrial dysfunction, leading to podocyte apoptosis. Therefore, inhibition of the ERK1/2-mTORC1 pathway could be a potential therapeutic and preventive target in proteinuric and chronic kidney diseases. PMID- 26565026 TI - Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence. AB - The activity of Ras is controlled by the interconversion between GTP- and GDP bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras.GTP with Ras.GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras.GDP, suggesting that Sos should actively promote unidirectional GDP -> GTP exchange on Ras in preference of passive homonucleotide exchange. Ras.GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras.GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID- 26565027 TI - Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid. AB - Tryptophan metabolites in the kynurenine pathway are up-regulated by pro inflammatory cytokines or glucocorticoids, and are linked to anti-inflammatory and immunosuppressive activities. In addition, they are up-regulated in pathologies such as cancer, autoimmune diseases, and psychiatric disorders. The molecular mechanisms of how kynurenine pathway metabolites cause these effects are incompletely understood. On the other hand, pro-inflammatory cytokines also up-regulate the amounts of tetrahydrobiopterin (BH4), an enzyme cofactor essential for the synthesis of several neurotransmitter and nitric oxide species. Here we show that xanthurenic acid is a potent inhibitor of sepiapterin reductase (SPR), the final enzyme in de novo BH4 synthesis. The crystal structure of xanthurenic acid bound to the active site of SPR reveals why among all kynurenine pathway metabolites xanthurenic acid is the most potent SPR inhibitor. Our findings suggest that increased xanthurenic acid levels resulting from up regulation of the kynurenine pathway could attenuate BH4 biosynthesis and BH4 dependent enzymatic reactions, linking two major metabolic pathways known to be highly up-regulated in inflammation. PMID- 26565028 TI - A Revised Mechanism for Human Cyclooxygenase-2. AB - The mechanism of omega-6 polyunsaturated fatty acid oxidation by wild-type cyclooxygenase 2 and the Y334F variant, lacking a conserved hydrogen bond to the catalytic tyrosyl radical/tyrosine, was examined for the first time under physiologically relevant conditions. The enzymes show apparent bimolecular rate constants and deuterium kinetic isotope effects that increase in proportion to co substrate concentrations before converging to limiting values. The trends exclude multiple dioxygenase mechanisms as well as the proposal that initial hydrogen atom abstraction from the fatty acid is the first irreversible step in catalysis. Temperature dependent kinetic studies reinforce the novel finding that hydrogen transfer from the reduced catalytic tyrosine to a terminal peroxyl radical is the first irreversible step that controls regio- and stereospecific product formation. PMID- 26565029 TI - Synthetic Antibodies Inhibit Bcl-2-associated X Protein (BAX) through Blockade of the N-terminal Activation Site. AB - The BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Pro-apoptotic Bcl-2-associated X protein (BAX) is an executioner protein of the BCL-2 family that represents the gateway to mitochondrial apoptosis. Following cellular stresses that induce apoptosis, cytosolic BAX is activated and translocates to the mitochondria, where it inserts into the mitochondrial outer membrane to form a toxic pore. How the BAX activation pathway proceeds and how this may be inhibited is not yet completely understood. Here we describe synthetic antibody fragments (Fabs) as structural and biochemical probes to investigate the potential mechanisms of BAX regulation. These synthetic Fabs bind with high affinity to BAX and inhibit its activation by the BH3-only protein tBID (truncated Bcl2 interacting protein) in assays using liposomal membranes. Inhibition of BAX by a representative Fab, 3G11, prevented mitochondrial translocation of BAX and BAX-mediated cytochrome c release. Using NMR and hydrogen-deuterium exchange mass spectrometry, we showed that 3G11 forms a stoichiometric and stable complex without inducing a significant conformational change on monomeric and inactive BAX. We identified that the Fab-binding site on BAX involves residues of helices alpha1/alpha6 and the alpha1-alpha2 loop. Therefore, the inhibitory binding surface of 3G11 overlaps with the N-terminal activation site of BAX, suggesting a novel mechanism of BAX inhibition through direct binding to the BAX N-terminal activation site. The synthetic Fabs reported here reveal, as probes, novel mechanistic insights into BAX inhibition and provide a blueprint for developing inhibitors of BAX activation. PMID- 26565030 TI - MAP1S Protein Regulates the Phagocytosis of Bacteria and Toll-like Receptor (TLR) Signaling. AB - Phagocytosis is a critical cellular process for innate immune defense against microbial infection. The regulation of phagocytosis process is complex and has not been well defined. An intracellular molecule might regulate cell surface initiated phagocytosis, but the underlying molecular mechanism is poorly understood (1). In this study, we found that microtubule-associated protein 1S (MAP1S), a protein identified recently that is involved in autophagy (2), is expressed primarily in macrophages. MAP1S-deficient macrophages are impaired in the phagocytosis of bacteria. Furthermore, we demonstrate that MAP1S interacts directly with MyD88, a key adaptor of Toll-like receptors (TLRs), upon TLR activation and affects the TLR signaling pathway. Intriguingly, we also observe that, upon TLR activation, MyD88 participates in autophagy processing in a MAP1S dependent manner by co-localizing with MAP1 light chain 3 (MAP1-LC3 or LC3). Therefore, we reveal that an intracellular autophagy-related molecule of MAP1S controls bacterial phagocytosis through TLR signaling. PMID- 26565031 TI - Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage. AB - Complement activation, oxidative damage, and activation of the NLRP3 inflammasome have been implicated in retinal pigment epithelium (RPE) pathology in age-related macular degeneration (AMD). Following priming of RPE cells, the NLRP3 inflammasome can be activated by various stimuli such as lipofuscin-mediated photooxidative damage to lysosomal membranes. We investigated whether products of complement activation are capable of providing the priming signal for inflammasome activation in RPE cells. We found that incubation of primary human RPE cells and ARPE-19 cells with complement-competent human serum resulted in up regulation of C5a receptor, but not C3a receptor. Furthermore, human serum induced expression of pro-IL-1beta and enabled IL-1beta secretion in response to lipofuscin phototoxicity, thus indicating inflammasome priming. Complement heat inactivation, C5 depletion, and C5a receptor inhibition suppressed the priming effect of human serum whereas recombinant C5a likewise induced priming. Conditioned medium of inflammasome-activated RPE cells provided an additional priming effect that was mediated by the IL-1 receptor. These results identify complement activation product C5a as a priming signal for RPE cells that allows for subsequent inflammasome activation by stimuli such as lipofuscin-mediated photooxidative damage. This molecular pathway provides a functional link between key factors of AMD pathogenesis including lipofuscin accumulation, photooxidative damage, complement activation, and RPE degeneration and may provide novel therapeutic targets in this disease. PMID- 26565032 TI - In Vitro Characterization of the Type I Toxin-Antitoxin System bsrE/SR5 from Bacillus subtilis. AB - BsrE/SR5 is a new type I toxin/antitoxin system located on the prophage-like region P6 of the Bacillus subtilis chromosome. The bsrE gene encoding a 30-amino acid hydrophobic toxin and the antitoxin gene sr5 overlap at their 3' ends by 112 bp. Overexpression of bsrE causes cell lysis on agar plates. Here, we present a detailed in vitro analysis of bsrE/SR5. The secondary structures of SR5, bsrE mRNA, and the SR5/bsrE RNA complex were determined. Apparent binding rate constants (kapp) of wild-type and mutated SR5 species with wild-type bsrE mRNA were calculated, and SR5 regions required for efficient inhibition of bsrE mRNA narrowed down. In vivo studies confirmed the in vitro data but indicated that a so far unknown RNA binding protein might exist in B. subtilis that can promote antitoxin/toxin RNA interaction. Using time course experiments, the binding pathway of SR5 and bsrE RNA was elucidated. A comparison with the previously well characterized type I TA system from the B. subtilis chromosome, bsrG/SR4, reveals similarities but also significant differences. PMID- 26565044 TI - Adult idiopathic occlusion of Monro foramina: Intraoperative endoscopic reinterpretation of radiological data and review of the literature. PMID- 26565033 TI - The SUMO (Small Ubiquitin-like Modifier) Ligase PIAS3 Primes ATR for Checkpoint Activation. AB - The maintenance of genomic stability relies on the concerted action of DNA repair and DNA damage signaling pathways. The PIAS (protein inhibitor of activated STAT) family of SUMO (small ubiquitin-like modifier) ligases has been implicated in DNA repair, but whether it plays a role in DNA damage signaling is still unclear. Here, we show that the PIAS3 SUMO ligase is important for activation of the ATR (ataxia telangiectasia and Rad3 related)-regulated DNA damage signaling pathway. PIAS3 is the only member of the PIAS family that is indispensable for ATR activation. In response to different types of DNA damage and replication stress, PIAS3 plays multiple roles in ATR activation. In cells treated with camptothecin (CPT), PIAS3 contributes to formation of DNA double-stranded breaks. In UV (ultraviolet light)- or HU (hydroxyurea)-treated cells, PIAS3 is required for efficient ATR autophosphorylation, one of the earliest events during ATR activation. Although PIAS3 is dispensable for ATRIP (ATR-interacting protein) SUMOylation and the ATR-ATRIP interaction, it is required for maintaining the basal kinase activity of ATR prior to DNA damage. In the absence of PIAS3, ATR fails to display normal kinase activity after DNA damage, which accompanies with reduced phosphorylation of ATR substrates. Together, these results suggest that PIAS3 primes ATR for checkpoint activation by sustaining its basal kinase activity, revealing a new function of the PIAS family in DNA damage signaling. PMID- 26565046 TI - Retraction Notice to: Grizzly Bears Exhibit Augmented Insulin Sensitivity while Obese Prior to a Reversible Insulin Resistance during Hibernation. PMID- 26565045 TI - Women in Metabolism: Part II. AB - The "Rosies" of Cell Metabolism are back for the second part of the "Women in Metabolism" series. In continuing our celebrations of Cell Metabolism's 10th anniversary, we are happy to present 15 new fascinating stories, revealing the passion, dedication, and words of wisdom from women leaders in the metabolism field. PMID- 26565047 TI - Non-profit organizations: Scientists on a mission. PMID- 26565048 TI - This is a new book series entitled Neuroscience and Respiration. Introduction. PMID- 26565049 TI - [Not Available]. PMID- 26565050 TI - [Not Available]. PMID- 26565051 TI - Electrosurgery: what do young surgeons need to know? PMID- 26565052 TI - Medicine in small doses. PMID- 26565053 TI - Info card for surgery waiting room improves satisfaction. AB - A hospital is reporting improved patient satisfaction from providing an information card in the surgery department. The card includes expected wait times. The card is provided by the patient transport team. Telephone numbers are included for more information. Staff update family members hourly during surgery. PMID- 26565054 TI - Waiting room card reduces family anxiety. PMID- 26565055 TI - Compliance with standing orders, protocol rule can be difficult. PMID- 26565057 TI - IOM says diagnosis errors underappreciated. PMID- 26565056 TI - Diagnosis errors are a system problem, not just doctor's fault. AB - The Institute of Medicine has issued a report calling on the medical community to more effectively address diagnostic errors. Reducing these errors will require a collaborative approach. Diagnostic errors are not typically caused by only a physician's error. Radiologists and pathologists should be more involved with diagnoses. Risk managers should treat diagnostic errors as a system problem. PMID- 26565058 TI - NLRB says nurses entitled to union representation at peer review. PMID- 26565059 TI - Sentinel Event Alert focuses on patient falls. PMID- 26565061 TI - [Periconceptional folic acid prophylaxis and neural tube defects]. AB - Neural tube defects (NTD) affect 60-70 pregnancies each year in Denmark. Folic acid (FA) intake can reduce the risk of NTD in pregnancy. The Danish Health and Medicines Authority recom-mends Danish women to take 0.4 mg of FA daily periconcep-tionally. Several studies have found low compliance regarding FA supplementation. In more than 70 countries around the world FA fortification of food products has been introduced and in USA and Canada this has lead to a decrease in NTD. FA fortification has not yet been introduced in Denmark. A revision of national Danish recommendations is needed. PMID- 26565062 TI - Minimal evolution time and quantum speed limit of non-Markovian open systems. AB - We derive a sharp bound as the quantum speed limit (QSL) for the minimal evolution time of quantum open systems in the non-Markovian strong-coupling regime with initial mixed states by considering the effects of both renormalized Hamiltonian and dissipator. For a non-Markovian quantum open system, the possible evolution time between two arbitrary states is not unique, among the set of which we find that the minimal one and its QSL can decrease more steeply by adjusting the coupling strength of the dissipator, which thus provides potential improvements of efficiency in many quantum physics and quantum information areas. PMID- 26565063 TI - The socioeconomic impact of international aid: a qualitative study of healthcare recovery in post-earthquake Haiti and implications for future disaster relief. AB - We assessed healthcare provider perspectives of international aid four years after the Haiti Earthquake to better understand the impact of aid on the Haitian healthcare system and learn best practices for recovery in future disaster contexts. We conducted 22 semi-structured interviews with the directors of local, collaborative, and aid-funded healthcare facilities in Leogane, Haiti. We coded and analysed the interviews using an iterative method based on a grounded theory approach of data analysis. Healthcare providers identified positive aspects of aid, including acute emergency relief, long-term improved healthcare access, and increased ease of referrals for low-income patients. However, they also identified negative impacts of international aid, including episodes of poor quality care, internal brain drain, competition across facilities, decrease in patient flow to local facilities, and emigration of Haitian doctors to abroad. As Haiti continues to recover, it is imperative for aid institutions and local healthcare facilities to develop a more collaborative relationship to transition acute relief to sustainable capacity building. In future disaster contexts, aid institutions should specifically utilise quality of care metrics, NGO Codes of Conduct, Master Health Facility Lists, and sliding scale payment systems to improve disaster response. PMID- 26565064 TI - The degradation behaviour of nine diverse contaminants in urban surface water and wastewater prior to water treatment. AB - An increasing diversity of emerging contaminants are entering urban surface water and wastewater, posing unknown risks for the environment. One of the main contemporary challenges in ensuring water quality is to design efficient strategies for minimizing such risks. As a first step in such strategies, it is important to establish the fate and degradation behavior of contaminants prior to any engineered secondary water treatment. Such information is relevant for assessing treatment solutions by simple storage, or to assess the impacts of contaminant spreading in the absence of water treatment, such as during times of flooding or in areas of poor infrastructure. Therefore in this study we examined the degradation behavior of a broad array of water contaminants in actual urban surface water and wastewater, in the presence and absence of naturally occurring bacteria and at two temperatures. The chemicals included caffeine, sulfamethoxazole, carbamazepine, atrazine, 17beta-estradiol, ethinylestradiol, diclofenac, desethylatrazine and norethindrone. Little information on the degradation behavior of these pollutants in actual influent wastewater exist, nor in general in water for desethylatrazine (a transformation product of atrazine) and the synthetic hormone norethindrone. Investigations were done in aerobic conditions, in the absence of sunlight. The results suggest that all chemicals except estradiol are stable in urban surface water, and in waste water neither abiotic nor biological degradation in the absence of sunlight contribute significantly to the disappearance of desethylatrazine, atrazine, carbamazepine and diclofenac. Biological degradation in wastewater was effective at transforming norethindrone, 17beta-estradiol, ethinylestradiol, caffeine and sulfamethoxazole, with measured degradation rate constants k and half-lives ranging respectively from 0.0082-0.52 d(-1) and 1.3-85 days. The obtained degradation data generally followed a pseudo-first-order-kinetic model. This information can be used to model degradation prior to water treatment. PMID- 26565065 TI - Naringenin ameliorates renal and platelet purinergic signalling alterations in high-cholesterol fed rats through the suppression of ROS and NF-kappaB signaling pathways. AB - Naringenin (NGEN) is a natural flavonoid aglycone of naringin that has been reported to have a wide range of pharmacological properties, such as antioxidant activity and free radical scavenging capacity. The aim of this study was to investigate the protective effect of NGEN on oxidative and inflammatory parameters, as well as to evaluate the hydrolysis of adenine nucleotides in kidney and platelet membranes of rats exposed to a hypercholesterolemic diet (HCD) for 90 days. Kidney oxidative stress and mRNA expression of the ectonucleoside triphosphate diphosphohydrolases (NTPDases), ecto-5'-nucleotidase (CD73), inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and the nuclear factor kappa B (NF-kappaB) genes were evaluated by real time RT-PCR. The co-administration of NGEN (50 mg kg(-1)) for 90 days significantly prevented renal failure in HCD rats as indicated by an improvement of renal markers. Histopathological observation findings are also consistent with these effects. Moreover, NGEN (50 mg kg(-1)) significantly decreased the lipid profile and inhibited pro-oxidant and inflammation marker levels in the kidney of HCD rats. Furthermore, the NTPDase activities were significantly decreased in platelets and kidney membranes of HCD-treated rats and these alterations were improved by NGEN. In conclusion, this study suggests that naringenin can potentially improve the renal failure and platelet alterations observed in rats fed a hypercholesterolemic diet probably through its antioxidant effects. PMID- 26565066 TI - Delaying diagnostic procedure significantly increases mortality in patients with invasive mucormycosis. AB - Invasive mucormycosis is an uncommon but increasing life-threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% (n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality (P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study (P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43-10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease. PMID- 26565067 TI - Antibodies as means for selective mass spectrometry. AB - For protein analysis of biological samples, two major strategies are used today; mass spectrometry (MS) and antibody-based methods. Each strategy offers advantages and drawbacks. However, combining the two using an immunoenrichment step with MS analysis brings together the benefits of each method resulting in increased sensitivity, faster analysis and possibility of higher degrees of multiplexing. The immunoenrichment can be performed either on protein or peptide level and quantification standards can be added in order to enable determination of the absolute protein concentration in the sample. The combination of immunoenrichment and MS holds great promise for the future in both proteomics and clinical diagnostics. This review describes different setups of immunoenrichment coupled to mass spectrometry and how these can be utilized in various applications. PMID- 26565068 TI - Development, validation and application of a fast analytical methodology for the simultaneous determination of DNA- and RNA-derived urinary nucleosides by liquid chromatography coupled to tandem mass spectrometry. AB - In the present work we report the development and validation of a fast liquid chromatography-mass spectrometry method for the simultaneous determination of endogenous nucleosides derived from DNA and RNA in urine. The target compounds were 2'-deoxyguanosine and 8-hydroxy-2'-deoxyguanosine, derived from DNA, and the analogue 8-hydroxyguanosine, derived from RNA, together with adenosine, 1 methyladenosine, 7-methylguanosine and inosine. The method is based on the use of a chromatographic column packed with superficially porous particles for high efficiency separation; further detection by MS/MS was accomplished with a triple quadrupole-mass spectrometer for analyte identification and accurate quantification. As a preliminary purification step, we developed a new procedure based on solid-phase extraction (SPE) with a mixed-sorbent prepared from three polymeric materials that facilitated the isolation of modified nucleosides, such as 2-deoxynucleosides, that are not retained by phenylboronic acid-based SPE. The proposed approach (SPE prior to LC-MS/MS) was validated in human urine in terms of linearity, the limit of detection, the limit of quantification, accuracy, recovery, repeatability, reproducibility and matrix-effects. For the SPE step, intra-day and inter-cartridge reproducibility were evaluated in natural and spiked urine samples, being +/- 16.9% or below, with recoveries in the 74-125% range. No significant matrix effects were found in further MS/MS detection. The application of the present method to urine from healthy smoker and non-smoker volunteers is also reported in order to test its usefulness as a tool for clinical and toxicological trials. PMID- 26565069 TI - Spatial distribution patterns of ammonia-oxidizing archaea abundance in subtropical forests at early and late successional stages. AB - Characterizing the spatial distribution patterns of soil microorganisms is helpful in understanding the biogeochemical processes they perform, but has been less studied relative to those of macroorganisms. In this study, we investigated and compared the spatially explicit distribution patterns of ammonia-oxidizing archaea (AOA) abundance and the influential factors between an early (ES) and a late successional (LS) subtropical forest stand. The average AOA abundance, vegetational attributes, and soil nutrient contents were mostly greater in the LS than the ES stand (P = 0.085 or smaller), but their spatial variations were more pronounced in the ES than the LS stand. The spatial distribution patches of AOA abundance were smaller and more irregular in the ES stand (patch size <50 m) than in the LS stand (patch size about 120 m). Edaphic and vegetational variables contributed more to the spatial variations of AOA abundance for the ES (9.3%) stand than for LS stand, whereas spatial variables (MEMs) were the main contributors (62%) for the LS stand. These results suggest that environmental filtering likely influence the spatial distribution of AOA abundance at early successional stage more than that at late successional stage, while spatial dispersal is dominant at late successional stage. PMID- 26565070 TI - The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities. AB - The contact activation system (CAS) and kallikrein/kinin system (KKS) are older recognized biochemical pathways that include several proteins that skirt the fringes of the blood coagulation, fibrinolytic, complement and renin-angiotensin fields. These proteins initially were proposed as part of the hemostatic pathways because their deficiencies are associated with prolonged clinical assays. However, the absence of bleeding states with deficiencies of factor XII (FXII), prekallikrein (PK) and high-molecular-weight kininogen indicates that the CAS and KKS do not contribute to hemostasis. Since the discovery of the Hageman factor 60 years ago much has been learned about the biochemistry, cell biology and animal physiology of these proteins. The CAS is a pathophysiologic surface defense mechanism against foreign proteins, organisms and artificial materials. The KKS is an inflammatory response mechanism. Targeting their activation through FXIIa or plasma kallikrein inhibition when blood interacts with the artificial surfaces of modern interventional medicine or in acute attacks of hereditary angioedema restores vascular homeostasis. FXII/FXIIa and products that arise with PK deficiency also offer novel ways to reduce arterial and venous thrombosis without an effect on hemostasis. In summary, there is revived interest in the CAS and KKS due to better understanding of their activities. The new appreciation of these systems will lead to several new therapies for a variety of medical disorders. PMID- 26565072 TI - Ten Years of Linear Endobronchial Ultrasound: Evidence of Efficacy, Safety and Cost-effectiveness. AB - Real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) is one of the major landmarks in the history of bronchoscopy. In the 10 years since it was introduced, a vast body of literature on the procedure and its results support the use of this technique in the study of various mediastinal and pulmonary lesions. This article is a comprehensive, systematic review of all the available scientific evidence on the more general indications for this technique. Results of specific studies on efficacy, safety and cost-effectiveness available to date are examined. The analysis shows that EBUS-TBNA is a safe, cost-effective technique with a high grade of evidence that is a valuable tool in the diagnosis and mediastinal staging of patients with suspected or confirmed lung cancer. However, more studies are needed to guide decision-making in the case of a negative result. Evidence on the role of EBUS-TBNA in the diagnosis of sarcoidosis and extrathoracic malignancies is also high, but much lower when used in the study of tuberculosis, lymphoma and for the re-staging of lung cancer after neoadjuvant chemotherapy. Nevertheless, due to its good safety record and lack of invasiveness compared to surgical techniques, the grade of evidence for recommending EBUS-TBNA as the initial diagnostic test in patients with these diseases is very high in most cases. PMID- 26565071 TI - Efficacy and safety of tacrolimus compared with ciclosporin-A in renal transplantation: 7-year observational results. AB - The European Tacrolimus versus Ciclosporin-A Microemulsion (CsA-ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months. Primary endpoints of this investigator-initiated, observational 7-year follow-up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, and patient death). We analyzed data from the original intent-to-treat population (n = 557; 286 tacrolimus, 271 CsA-ME). A total of 237 tacrolimus and 208 CsA-ME patients provided data. At 7 years, Kaplan-Meier estimated rates of patients free from BPAR were 77.1% in the tacrolimus arm and 59.9% in the CsA-ME arm, graft survival rates amounted to 82.6% and 80.6%, and patient survival rates to 89.9% and 88.1%. Estimated combined endpoint-free survival rates were 60.2% in the tacrolimus arm and 47.0% in the CsA-ME arm (P = <0.0001). A higher number of patients from the CsA-ME arm crossed over to tacrolimus during 7 year follow-up: 19.7% vs. 7.9% (P = <0.002). More patients in the tacrolimus group stopped steroids and received immunosuppressive monotherapy. Significantly, more CsA-ME patients received lipid lowering medication and experienced cosmetic and cardiovascular adverse events. Tacrolimus-treated renal transplant recipients had significantly higher combined endpoint-free survival rates mainly driven by lower acute rejection rates despite less immunosuppressive medication at 7 years. PMID- 26565073 TI - Phonon limited superconducting correlations in metallic nanograins. AB - Conventional superconductivity is inevitably suppressed in ultra-small metallic grains for characteristic sizes smaller than the Anderson limit. Experiments have shown that above the Anderson limit the critical temperature may be either enhanced or reduced when decreasing the particle size, depending on the superconducting material. In addition, there is experimental evidence that whether an enhancement or a reduction is found depends on the strength of the electron-phonon interaction in the bulk. We reveal how the strength of the e-ph interaction interplays with the quantum-size effect and theoretically obtain the critical temperature of the superconducting nanograins in excellent agreement with experimental data. We demonstrate that strong e-ph scattering smears the peak structure in the electronic density-of-states of a metallic grain and enhances the electron mass, and thereby limits the highest Tc achievable by quantum confinement. PMID- 26565074 TI - Home use of misoprostol for early medical abortion in a low resource setting: secondary analysis of a randomized controlled trial. AB - INTRODUCTION: Although home use of misoprostol for early medical abortion is considered to be safe, effective and feasible, it has not become standard service delivery practice. The aim of this study was to compare the efficacy, safety, and acceptability of home use of misoprostol with clinic misoprostol in a low resource setting. MATERIAL AND METHODS: This was a secondary analysis of a randomized controlled trial conducted in six primary care clinics in India. Women seeking medical abortion within up to nine gestational weeks (n = 731) received mifepristone in the clinic and were allocated either to home or clinic administration of misoprostol. Follow-up contact was after 10-15 days. RESULTS: Of 731 participants, 73% were from rural areas and 55% had no formal education. Complete abortion rates in the home and clinic misoprostol groups were 94.2 and 94.4%, respectively. The rate of adverse events was similar in both groups (0.3%). A greater proportion of home users (90.2%) said that they would opt for misoprostol at home in the event of a future abortion compared with clinic users (79.7%) who would opt for misoprostol at the clinic in a similar situation (p = 0.0002). Ninety-six percent women using misoprostol at home or in the clinic were satisfied with their abortion experience. CONCLUSIONS: Home-use of misoprostol for early medical abortion is as effective and acceptable as clinic use, in low resource settings. Women should be offered a choice of this option regardless of distance of their residence from the clinic and communication facilities. PMID- 26565075 TI - Diastereoselective Synthesis of Glycosyl Phosphates by Using a Phosphorylase Phosphatase Combination Catalyst. AB - Sugar phosphates play an important role in metabolism and signaling, but also as constituents of macromolecular structures. Selective phosphorylation of sugars is chemically difficult, particularly at the anomeric center. We report phosphatase catalyzed diastereoselective "anomeric" phosphorylation of various aldose substrates with alpha-D-glucose 1-phosphate, derived from phosphorylase-catalyzed conversion of sucrose and inorganic phosphate, as the phosphoryl donor. Simultaneous and sequential two-step transformations by the phosphorylase phosphatase combination catalyst yielded glycosyl phosphates of defined anomeric configuration in yields of up to 70 % based on the phosphate applied to the reaction. An efficient enzyme-assisted purification of the glycosyl phosphate products from reaction mixtures was established. PMID- 26565076 TI - Severe Vincristine-induced Neuropathic Pain in a CYP3A5 Nonexpressor With Reduced CYP3A4/5 Activity: Case Study. AB - PURPOSE: Peripheral neuropathy is a frequent vincristine-induced adverse effect. Vincristine is a substrate of P-glycoprotein and is metabolized by the cytochrome P-450 (CYP) 3A5 and 3A4 isoforms, with CYP3A5 contributing to 75% of the intrinsic clearance of vincristine. Alterations in the function of these proteins may lead to an increase in vincristine toxicity. CYP3A5 nonexpressor status has been associated with vincristine-induced peripheral neuropathy. The severity of neuropathy has been reported to be inversely correlated to vincristine metabolite concentrations. Recently, the presence of a mutation in the CEP72 gene, which encodes for a protein involved in microtubule formation, has also been associated with vincristine-induced peripheral neuropathy. However, a clear correlation between genetic polymorphisms and vincristine toxicity has not been established. METHODS: Here we report the case of a 21-year old patient in whom severe neuropathic pain developed after vincristine treatment. FINDINGS: The patient was a CYP3A5 nonexpressor and presented with reduced CYP3A4/5 functional activity, a likely reason for the occurrence of the adverse event, as genotyping showed that his status was wild type for the ABCB1 and CEP72 genes. IMPLICATIONS: CYP phenotype and genotype may explain the occurrence of severe neuropathy in some patients treated with vincristine. PMID- 26565077 TI - Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo controlled Trial. AB - PURPOSE: Dalfampridine extended-release (ER) tablets 10 mg BID have been approved for use in improving walking in people with multiple sclerosis (MS). This subgroup analysis evaluated the effects of dalfampridine ER 5 and 10 mg BID on distance walked, as assessed using the 6-minute walk (6MW) test. METHODS: This analysis of data from a randomized, placebo-controlled, double-blind study (N = 430) included only the 153 patients with 6MW data available. Participants (aged 18-70 years) were randomly assigned in a 1:1:1 ratio to receive dalfampridine ER 5 or 10 mg or placebo, BID for 4 weeks. The 6MW was used for assessing walking distance at baseline and 2 weeks after the start of treatment at the 26 study sites that were able to perform this test. Participants were administered the 12 item MS Walking Scale (MSWS-12), a patient-reported measure of the impact of MS on walking. Post hoc outcomes included the percentages of patients who achieved an increase from baseline in 6MW distance of >=20% and who achieved a minimal clinically important difference (MCID) from baseline in 6MW distance, defined as >=+55 m. Changes from baseline in walking speed (MSWS-12) were compared, stratified by subgroup that achieved >=20% versus <20% improvement on the 6MW. The correlation between change in walking speed over time and subgroup (by change in distance walked) was evaluated. The tolerability of dalfampridine was assessed based on the prevalence of treatment-emergent adverse events (TEAEs). FINDINGS: In the post hoc analysis, the percentage of patients with an improvement in 6MW distance that met or exceeded the MCID was significantly greater with dalfampridine ER 10 mg BID relative to placebo (37.3% vs 12.2%; nominal P = 0.004). Similarly, the percentage with an improvement in 6MW distance of >=20% was significantly greater with dalfampridine 10 mg BID relative to placebo (45.1% vs 14.3%; nominal P < 0.001). Regardless of treatment allocation, improvement in MSWS-12 was significantly greater in the subgroup that achieved a >=20% improvement on the 6MW compared with the subgroup with <20% improvement (mean changes, -15.5 vs -7.2; nominal P = 0.041). The prevalences and types of TEAEs were consistent with those reported in previous studies. IMPLICATIONS: Based on the MCID for 6MW, the use of dalfampridine ER 10 mg BID but not 5 mg BID was associated with statistically significant and clinically meaningful improvements in walking relative to placebo. The correlation between improvement on MSWS-12 and the 20% increase in 6MW distance suggests that an improvement on MSWS-12 is clinically relevant. These results, although highlighting a lack of efficacy of dalfampridine ER 5 mg BID, suggest that the 10-mg BID dose is effective for improving walking speed, as observed on short timed-walk tests, and for increasing distance walked over longer timed-walk periods. ClinicalTrials.gov identifier: NCT01328379. PMID- 26565078 TI - Phononic crystal surface mode coupling and its use in acoustic Doppler velocimetry. AB - It is numerically shown that surface modes of two-dimensional phononic crystals, which are Bloch modes bound to the interface between the phononic crystal and the surrounding host, can couple back and forth between the surfaces in a length scale determined by the separation of two surfaces and frequency. Supercell band structure computations through the finite-element method reveal that the surface band of an isolated surface splits into two bands which support either symmetric or antisymmetric hybrid modes. When the surface separation is 3.5 times the lattice constant, a coupling length varying between 30 and 48 periods can be obtained which first increases linearly with frequency and, then, decreases rapidly. In the linear regime, variation of coupling length can be used as a means of measuring speeds of objects on the order of 0.1m/s by incorporating the Doppler shift. Speed sensitivity can be improved by increasing surface separation at the cost of larger device sizes. PMID- 26565079 TI - Cultural Safety and Providing Care to Aboriginal patients in the Emergency Department. PMID- 26565080 TI - The Kinect Recording System for objective three- and four-dimensional breast assessment with image overlays. AB - INTRODUCTION: We investigated the application of the validated portable Kinect camera for three- and four-dimensional breast assessment in female life models. METHOD: Breast images from six life models were captured using the Kinect camera. Capture was conducted with taking three different arm positions while standing upright: with the arms straight down, straight up to the side at 90 degrees and straight all the way up. Images of the volunteers were superimposed on each other. Digital linear distances between sternal notch and nipple-areola complexes were obtained and compared. The views of plastic and breast surgeons to arm positions were questioned. An example for clinical application was provided. RESULTS: Successful capture of images of the female life breast models was achieved. Digital breast measurements at the three different arm positions revealed considerable variation in linear distances measured on the images obtained with the Kinect camera. The dynamic of breast movements could be demonstrated by image overlay and the first ever four-dimensional breast assessment was demonstrated. Fourteen plastic and breast surgeons were found to have nine different opinions regarding their favoured arm positions for breast capture. Even though precision of image sharpness still needs improvement, the images were satisfactory for clinical patient use. The Kinect data were shown to be applicable to surgery planning by designing a planar flap from the 3D mesh. CONCLUSION: The portable and low-cost Kinect camera proved to be easy to use for the first application in life models for three- and four-dimensional breast assessment. PMID- 26565081 TI - Probiotic yeast Kluyveromyces marxianus CIDCA 8154 shows anti-inflammatory and anti-oxidative stress properties in in vivo models. AB - Inflammatory bowel diseases (IBDs) are complex affections with increasing incidence worldwide. Multiple factors are involved in the development and maintenance of the symptoms including enhanced oxidative stress in intestinal mucosa. The conventional therapeutic approaches for IBDs are based on the use anti-inflammatory drugs with important collateral effects and partial efficacy. In the present work we tested the anti-inflammatory capacity of Kluyveromyces marxianus CIDCA 8154 in different models. In vitro, we showed that the pretreatment of epithelial cells with the yeast reduce the levels of intracellular reactive oxygen species. Furthermore, in a murine model of trinitro benzene sulfonic acid-induced colitis, yeast-treated animals showed a reduced histopathological score (P<0.05) and lower levels of circulating interleukin 6 (P<0.05). The capacity to modulate oxidative stress in vivo was assessed using a Caenorhabditis elegans model. The yeast was able to protect the nematodes from oxidative stress by modulating the SKN-1 transcription factor trough the DAF-2 pathway. These results indicate that K. marxianus CIDCA 8154 could control the intestinal inflammation and cellular oxidative stress. Deciphering the mechanisms of action of different probiotics might be useful for the rational formulation of polymicrobial products containing microorganisms targeting different anti inflammatory pathways. PMID- 26565082 TI - Probiotic supplementation influences faecal short chain fatty acids in infants at high risk for eczema. AB - The composition of the gut microbiota plays a role in the development of allergies. Based on the immunomodulating capacities of bacteria, various studies have investigated the potential role for probiotics in the prevention of childhood eczema. In a previous study we have shown that significantly less children developed eczema after probiotic supplementation (Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W52 and Lactococcus lactis W58, Ecologic((r))Panda) at three months of age as compared to controls. Here, metabolites in faecal samples of these 3-month old children were measured by (1)H nuclear magnetic resonance to investigate possible gut metabolic alterations. Lower amounts of short-chain fatty acids (SCFAs), succinate, phenylalanine and alanine were found in faecal samples of children later developing eczema, whereas the amounts of glucose, galactose, lactate and lactose were higher compared to the children not developing eczema. Although these differences were already present at the age of 3 months, eczema did not develop in the majority of children before the age of 1 year. Supplementation of multispecies probiotics seems to induce higher levels of lactate and SCFAs, and lower levels of lactose and succinate when compared with the placebo group. This might explain the temporary preventive effect of probiotics on the development of eczema. These results highlight the role bacterial metabolites may play in development of the immune system, even before clinical manifestations of allergic disease arise. PMID- 26565083 TI - In vitro evidence for efficacy in food intolerance for the multispecies probiotic formulation Ecologic(r) Tolerance (SyngutTM). AB - The beneficial effects of probiotics are currently the subject of extensive studies in health and medical research. The aim of this research was to specifically design a new probiotic formulation for supplementation in people suffering from food intolerance. The selection of strains was focussed on the capacity to influence mechanisms of action that are important in development of food intolerance with the following parameters measure: in vitro capacity to produce beta-galactosidase, in vitro strengthening of the epithelial barrier, in vitro stimulation of cytokines produced by regulatory T cells, in addition to assessing fundamental quality criteria (stability, gastrointestinal (GI) survival, multispecies concept, allergen-free). Ecologic(r)Tolerance/SyngutTM was subsequently developed consisting of a multispecies concept using 4 different probiotic strains (Bifidobacterium lactis W51, Lactobacillus acidophilus W22, Lactobacillus plantarum W21 and Lactococcus lactis W19). Each of these strains demonstrated ability to survive the GI-tract and strain specific effects in producing beta-galactosidase, strengthening the gut barrier function after immunological-induced stress and inhibiting Th2 cytokines (IL-4, IL-5 and IL-13 (>=50%), in addition to stimulating interleukin-10 levels; thus, providing in vitro evidence for the efficacy of the selected strains to provide beneficial effects in patients suffering from food intolerance. PMID- 26565084 TI - Effect of dietary supplementation of Bifidobacterium and Lactobacillus strains in Apis mellifera L. against Nosema ceranae. AB - Nosema ceranae is a widespread microsporidium of European honeybee Apis mellifera L. affecting bee health. The ban of Fumagillin-B (dicyclohexylammonium salt) in the European Union has driven the search for sustainable strategies to prevent and control the infection. The gut microbial symbionts, associated to the intestinal system of vertebrates and invertebrates and its impact on host health, are receiving increasing attention. In particular, bifidobacteria and lactobacilli, which are normal inhabitants of the digestive system of bees, are known to protect their hosts via antimicrobial metabolites, immunomodulation and competition. In this work, the dietary supplementation of gut bacteria was evaluated under laboratory conditions in bees artificially infected with the parasite and bees not artificially infected but evidencing a low natural infection. Supplemented bacteria were selected among bifidobacteria, previously isolated, and lactobacilli, isolated in this work from healthy honeybee gut. Four treatments were compared: bees fed with sugar syrup (CTR); bees fed with sugar syrup containing bifidobacteria and lactobacilli (PRO); bees infected with N. ceranae spores and fed with sugar syrup (NOS); bees infected with N. ceranae and fed with sugar syrup containing bifidobacteria and lactobacilli (NP). The sugar syrup, with or without microorganisms, was administered to bees from the first day of life for 13 days. N. ceranae infection was carried out individually on anesthetised 5-day-old bees. Eight days after infection, a significant (P<0.05) lower level of N. ceranae was detected by real-time PCR in both NP and PRO group, showing a positive effect of supplemented microorganisms in controlling the infection. These results represent a first attempt of application of bifidobacteria and lactobacilli against N. ceranae in honeybees. PMID- 26565085 TI - Weissella paramesenteroides WpK4 reduces gene expression of intestinal cytokines, and hepatic and splenic injuries in a murine model of typhoid fever. AB - Diarrhoea in piglets by Salmonella and other pathogens can be a serious health problem. Non-drug treatments such as probiotic microorganisms have various effects on the gastrointestinal microbiota dysbiosis and host immune system modulation. The aim of this study was to demonstrate the suitable use of Weissella paramesenteroides WpK4 strain isolated from healthy piglets as an alternative prophylactic or therapeutic treatment against Salmonella Typhimurium. Out of 37 lactic acid bacteria isolates, 24 strains belonging to the Weissella and Lactobacillus genera were analysed in vitro for desirable probiotic characteristics. The W. paramesenteroides WpK4 strain fulfilled all in vitro tests: resistance to acidic pH and bile salts, hydrophobic cell surface, antagonism against bacterial pathogens, H2O2 production and exopolysaccharide secretion, and non-transferable resistance to antibiotics. Mice fed with WpK4 showed no signs of bacterial translocation to the liver or spleen and decreased Salmonella translocation to these organs. Significantly, WpK4 intake attenuated the weight loss, fostered the preservation of intestinal architecture and integrity, and promoted survival in mice following infection with Salmonella Typhimurium. In addition, WpK4 modulated immune cellular response by inhibiting the production of pro-inflammatory cytokines and inducing anti-inflammatory mediators. These findings validate the probiotic properties of W. paramesenteroides WpK4 strain, and its eventual use in piglets. PMID- 26565086 TI - Selection, characterisation and evaluation of potential probiotic Lactobacillus spp. isolated from poultry droppings. AB - Aim of the present study was to characterise and evaluate probiotic potential of lactobacilli isolated from indigenous poultry. Lactobacilli were isolated from poultry droppings and identified by genus specific polymerase chain reaction and 16S rRNA gene sequencing. Isolates were characterised in vitro by their ability to tolerate low pH and bile salts, phytase activity, antimicrobial activity, antibiotic susceptibility profile, and autoaggregation and coaggregation with poultry gut pathogens. In vivo evaluation of selected isolates was done by their effect on the body weight gain and immune response of broiler chicks. Total of 90, one-day old chicks, were randomly divided in 9 groups and given selected lactobacilli alone and in combinations (108 cfu/bird, daily) from day 7 to day 35. Body weight gain and humoral immune response to New Castle Disease Virus (NDV) vaccine were determined weekly. Three lactobacilli isolates (SMP52, SMP64 and SMP70) were selected as potentially probiotic bacteria on the basis of in vitro characterisation and identified as Lactobacillus crispatus, Lactobacillus casei and L. crispatus, respectively. Chicks supplemented with 'SMP52', 'SMP64', 'SMP70' and 'SMP64+SMP70' and a commercial probiotic product (Protexin) showed significantly higher mean weight gain per bird (1,584+/-35.2, 1,629+/-30.6, 1,668+/-34.7, 1,619+/-29.5 and 1,576+/-31.7 g/bird, respectively) as compared to negative control group (1,394+/-26.7 g/bird), on day 35. SMP 70 also showed significantly higher geometric mean titre against NDV vaccine at day 21 as compared to negative control. It is concluded that L. crispatus SMP52, L. casei SMP64 and L. crispatus SMP70 are potential probiotic candidates which alone or in different combinations may increase body weight of broilers. PMID- 26565087 TI - Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans - towards treatment with probiotics. AB - Changes in the gut microbiota are associated with metabolic disorders, such as overweight and elevated blood glucose. Mouse studies have shown that gut microbiota can regulate metabolism with a mechanism related to gut barrier function. An impaired gut barrier permits the translocation of bacteria and their components which, when in contact with the sub-mucosal immune system, evoke metabolic inflammation and distract signalling in metabolically active tissues. Despite thorough research of the topic in animals, the hypothesis is yet to be proven in humans. Cross-sectional studies have shown that certain bacterial populations - such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Methanobrevibacter smithii and Christensenellaceae - are better represented in lean individuals compared to those who are overweight or metabolically unhealthy. Although these differences reflect those seen in mice, it is possible that they are caused by different dietary or other lifestyle habits. Diet has an indisputable influence on gut microbiota making it very difficult to draw conclusions on microbiota-host interactions from cross-sectional studies. Certain research areas do, however, indicate that gut microbiota could causally influence metabolism. Several studies show that antibiotic use in infancy increases body weight in later childhood. Also, probiotics are emerging as a potential therapy for metabolic syndrome. In fact, a handful of human studies and numerous animal studies show promise for probiotics in reducing blood glucose levels or improving insulin sensitivity. For weight management human evidence is scarcer. Nevertheless, it is becoming increasingly recognised that gut microbiota plays a part regulating metabolism, also in humans, which gives rise to novel opportunities for preventative and treatment strategies. PMID- 26565088 TI - Steady Progress in 2015. PMID- 26565089 TI - State of the Journal, 2015. AB - The American Journal of Occupational Therapy (AJOT) had a successful 2015. From September 2014 to September 2015, the number of manuscripts submitted had increased by 35%. Manuscripts were received from 23 countries, compared with 17 countries in 2014. AJOT continues to have the highest impact factor and to be the highest ranked of the occupational therapy journals listed in Journal Citation Reports. AJOT continues to focus on publishing research articles on aspects of occupational therapy among varied populations with diverse acute and chronic conditions. Additional changes for 2015 include new associate editors, a significantly enlarged pool of reviewers from across the globe, continuous publishing, pay-per-view, updated author guidelines, and the adoption of clinical trial registration requirements effective January 1, 2016. PMID- 26565090 TI - Engagement, Exploration, Empowerment. AB - Engagement, exploration, and empowerment are significant practice strategies used by occupational therapy practitioners as a means of getting to know what matters to clients and how to facilitate their participation in everyday life. Applied to the American Occupational Therapy Association (AOTA) as an organization, professional engagement, exploration of new service contexts, and empowerment of members to take an active role in shaping the profession's future are examined. This address, given at the 2015 AOTA Annual Convention & Expo, looks to the future in terms of engaging greater numbers of members; participating in Vision 2025, a strategic planning initiative that will be unveiled at the 2016 AOTA Annual Conference & Expo; and empowering members to achieve excellence in occupational therapy. PMID- 26565091 TI - A Career in Inquiry. AB - This article, based on the 52nd Eleanor Clarke Slagle lecture given at the 95th American Occupational Therapy Association Annual Conference & Expo, explores the concept of inquiry as the basis for a career and as an activity of daily living. Using the heliocentric theory and the space program at NASA as examples, the broad concept of inquiry is discussed, because it has led to important changes in society over the course of history. The article describes how a career as a clinician-scientist can be grounded in the concept of inquiry and explains how all occupational therapists and occupational therapy assistants can base their own careers in inquiry, using examples from the early history of the profession of occupational therapy and from work by current investigators. Practical suggestions applicable to every clinician are provided. PMID- 26565093 TI - Paying It Forward: Honoring Jane Case-Smith for Commitment to Occupational Therapy Education and Research. PMID- 26565094 TI - Multiple Treatments of Pediatric Constraint-Induced Movement Therapy (pCIMT): A Clinical Cohort Study. AB - Pediatric constraint-induced movement therapy (pCIMT) is one of the most efficacious treatments for children with cerebral palsy (CP). Distinctive components of pCIMT include constraint of the less impaired upper extremity (UE), high-intensity therapy for the more impaired UE (>= 3 hr/day, many days per week, for multiple weeks), use of shaping techniques combined with repetitive task practice, and bimanual transfer. A critical issue is whether multiple treatments of pCIMT produce additional benefit. In a clinical cohort (mean age = 31 mo) of 28 children with asymmetrical CP whose parents sought multiple pCIMT treatments, the children gained a mean of 13.2 (standard deviation [SD] = 4.2) new functional skills after Treatment 1; Treatment 2 produced a mean of 7.3 (SD = 4.7) new skills; and Treatment 3, 6.5 (SD = 4.2). These findings support the conclusion that multiple pCIMT treatments can produce clinically important functional gains for children with hemiparetic CP. PMID- 26565095 TI - Occupational Therapists' Opinions of Two Pediatric Constraint-Induced Movement Therapy Protocols. AB - OBJECTIVE: We sought to determine occupational therapists' opinions of two pediatric constraint-induced movement therapy (pCIMT) protocols. METHOD: A total of 272 therapists in pediatric rehabilitation clinics completed an electronic survey to determine their opinions of two published pCIMT protocols. In Protocol A, restraint is worn 24 hr/day on the nonparetic upper extremity (UE), and in clinic, therapist-supervised practice sessions occur 7 days/wk for 6 hr/day over 3 wk. In Protocol B, restraint is worn 2 hr/day on the nonparetic UE, and in clinic, therapist-supervised practice sessions occur 1 day/wk for 2 hr/day over 8 wk. RESULTS: The majority of participants reported moderate to high concerns about every facet of Protocol A. Conversely, >50% of participants reported low or no concerns about five of seven facets of Protocol B. CONCLUSION: This study adds to a growing body of evidence suggesting that therapists strongly prefer low duration pCIMT protocols. PMID- 26565096 TI - Behavioral and Physiological Factors Associated With Selective Eating in Children With Autism Spectrum Disorder. AB - Selective eating is common in children with autism spectrum disorder (ASD), but it is not yet well understood. The objectives of this study were to examine a new definition of selective eating, compare behavioral measures between children with ASD and selective eating and those without selective eating, and determine relationships among behavioral measures and measures of selective eating. Participants were assigned to groups on the basis of number of foods eaten compared with a population-based sample. Results of one-way multivariate analysis of variance indicated no overall effect of group for challenging behaviors, sensory reactivity, or repetitive behaviors. Between-participant tests indicated that scores for compulsive behaviors were significantly lower (p = .036) for the selective eating group. Correlations were moderately strong among variables relating to food intake and behavioral variables, but were not significant between selective eating and behavioral variables. Further research is needed to validate the definition of selective eating and to identify targets for intervention. PMID- 26565097 TI - Development of the Classroom Sensory Environment Assessment (CSEA). AB - The Classroom Sensory Environment Assessment (CSEA) is a tool that provides a means of understanding the impact of a classroom's sensory environment on student behavior. The purpose of the CSEA is to promote collaboration between occupational therapists and elementary education teachers. In particular, students with autism spectrum disorder included in general education classrooms may benefit from a suitable match created through this collaborative process between the sensory environment and their unique sensory preferences. The development of the CSEA has occurred in multiple stages over 2 yr. This article reports on descriptive results for 152 classrooms and initial reliability results. Descriptive information suggests that classrooms are environments with an enormous variety of sensory experiences that can be quantified. Visual experiences are most frequent. The tool has adequate internal consistency but requires further investigation of interrater reliability and validity. PMID- 26565098 TI - Handwriting Without Tears((r)): General Education Effectiveness Through a Consultative Approach. AB - OBJECTIVE: This study explores the effectiveness of the Handwriting Without Tears((r)) (HWT) kindergarten printing curriculum in general education through a consultative approach with occupational therapy. METHOD: One cohort of students was the control (n = 19), whereas two other cohorts were experimental groups learning printing through the HWT curriculum (n = 20 each). The Test of Handwriting Skills-Revised (THS-R) was used to collect end-of-year legibility scores for all cohorts. RESULTS: Both experimental groups individually and both experimental groups combined into one group outperformed the control group on all 10 of the THS-R subtests-scoring significantly higher (p < .05 using analysis of covariance controlling for age and gender) on 6 of the subtests for the former and 7 for the latter-and on overall score. Large treatment effects were found for the standard score for each experimental group (d = 0.81, 1.03, and 1.00). CONCLUSION: This study supports the consultative role of occupational therapy with teachers in general education for handwriting curriculum implementation and the success of HWT for printing instruction. PMID- 26565100 TI - Systematic Review of Yoga Interventions for Anxiety Reduction Among Children and Adolescents. AB - OBJECTIVE: Anxiety disorders are the most prevalent psychological disorders among children and youths. There is growing interest in intervention options for anxiety. Yoga is widely used in clinical, school, and community settings, but consolidated sources outlining its effectiveness in reducing anxiety are limited. METHOD: This systematic review examined the evidence base (1990-2014) for yoga interventions addressing anxiety among children and adolescents (ages 3-18 yr). RESULTS: We identified 2,147 references and found 80 articles that were eligible for full-text review. The final analysis included 16: 6 randomized controlled trials, 2 nonrandomized preintervention-postintervention control-group designs, 7 uncontrolled preintervention-postintervention studies, and 1 case study. CONCLUSION: Nearly all studies indicated reduced anxiety after a yoga intervention. However, because of the wide variety of study populations, limitations in some study designs, and variable outcome measures, further research is needed to enhance the ability to generalize and apply yoga to reduce anxiety. PMID- 26565099 TI - Building Capacity of Occupational Therapy Practitioners to Address the Mental Health Needs of Children and Youth: A Mixed-Methods Study of Knowledge Translation. AB - PURPOSE: We explored the meaning and outcomes of a 6-mo building capacity process designed to promote knowledge translation of a public health approach to mental health among pediatric occupational therapy practitioners participating in a Community of Practice. METHOD: A one-group (N = 117) mixed-methods design using a pretest-posttest survey and qualitative analysis of written reflections was used to explore the meaning and outcomes of the building capacity process. RESULTS: Statistically significant improvements (p < .02) in pretest-posttest scores of knowledge, beliefs, and actions related to a public health approach to mental health were found. Qualitative findings suggest that participation resulted in a renewed commitment to addressing children's mental health. CONCLUSION: The building capacity process expanded practitioner knowledge, renewed energy, and promoted confidence, resulting in change leaders empowered to articulate, advocate for, and implement practice changes reflecting occupational therapy's role in addressing children's mental health. PMID- 26565101 TI - Development and Psychometric Evaluation of the Vocational Fit Assessment (VFA). AB - OBJECTIVE: The objective of this study was to determine the psychometric properties of the Vocational Fit Assessment (VFA) by examining its factor structure and subscale reliability. METHOD: This prospective cross-sectional study used two surveys (one for worker abilities and one for job demands) to collect the data needed for the psychometric evaluation of the VFA. Latent parallel analysis and ordinal exploratory factor analysis were used to iteratively refine VFA subscales. RESULTS: Ten unidimensional subscales emerged from factor analysis of VFA items: (1) Cognitive Abilities, (2) Communication Skills, (3) Computer Skills, (4) Higher Task-Related Abilities, (5) Interpersonal Skills, (6) Lower Task-Related Abilities, (7) Physical Abilities, (8) Safety, (9) Self-Determination, and (10) Work Structure. Subscale internal consistency (ordinal alpha) was >=.86 for VFA for worker abilities and >=.77 for VFA for job demands. CONCLUSION: The unidimensional structure of VFA subscales and estimates of internal consistency lend initial evidence in support of their reliability and validity. PMID- 26565102 TI - Developing Occupation-Based Preventive Programs for Late-Middle-Aged Latino Patients in Safety-Net Health Systems. AB - Latino adults between ages 50 and 60 yr are at high risk for developing chronic conditions that can lead to early disability. We conducted a qualitative pilot study with 11 Latinos in this demographic group to develop a foundational schema for the design of health promotion programs that could be implemented by occupational therapy practitioners in primary care settings for this population. One-on-one interviews addressing routines and activities, health management, and health care utilization were conducted, audiotaped, and transcribed. Results of a content analysis of the qualitative data revealed the following six domains of most concern: Weight Management; Disease Management; Mental Health and Well Being; Personal Finances; Family, Friends, and Community; and Stress Management. A typology of perceived health-actualizing strategies was derived for each domain. This schema can be used by occupational therapy practitioners to inform the development of health-promotion lifestyle interventions designed specifically for late-middle-aged Latinos. PMID- 26565103 TI - Food Activities and Identity Maintenance Among Community-Living Older Adults: A Grounded Theory Study. AB - OBJECTIVE: Engaging in food activities and maintaining identity are each important for productive aging. This study explored the role of food activities in identity maintenance among community-living older adults. METHOD: We used a grounded theory approach to analyze data collected in semistructured interviews with 39 predominantly White, British older adults living in West London. RESULTS: Two lifelong food identities-"food lover" and "nonfoodie"-were maintained in the processes of participation and maintenance and threat and compensation. The process change in meaning and identity explained the development of a third food identity-"not bothered"-when participants experienced being alone at the table, deteriorating health, and worry about the cost of food. CONCLUSION: Food activities that are a pleasurable and important part of daily life contribute to the maintenance of important identities and mental well-being in older adults. PMID- 26565104 TI - Functional Deficits and Quality of Life Among Cancer Survivors: Implications for Occupational Therapy in Cancer Survivorship Care. AB - This study aimed to explore functional deficits and perceived quality of life (QoL) among cancer survivors. Sixty-six participants completed the Post Cancer Outcome Survey developed for the purpose of this study. The results indicated (1) modest to moderate degrees of functional deficits in 28 of the 70 items measuring areas of occupation, performance skills, body functions, and psychosocial well being within the first year after cancer treatment; (2) significantly lower perceived QoL during the first year of survivorship compared with that before diagnosis, at present, and 5 yr hereafter (p < .001); (3) significant moderate negative correlations between the reported functional deficits and QoL (rs = -.45 to -.57); and (4) a very low percentage of participants (4.5%) receiving occupational therapy during the first year posttreatment. Functional difficulties and compromised QoL identified in this study indicate the need for occupational therapy among cancer survivors. Increasing clients' awareness of occupational therapy for postcancer care is also suggested. PMID- 26565105 TI - Development and Preliminary Reliability of the Functional Upper Extremity Levels (FUEL). AB - OBJECTIVE: The Functional Upper Extremity Levels (FUEL) is a new classification tool to assess a person's upper-extremity functional and physical performance after sustaining a stroke. The aim of this preliminary study was to develop the tool and determine its content validity and interrater reliability. METHOD: Forty four licensed occupational therapists ranging in years of experience from 6 mo to 16 yr participated in this study. A two-phase study was conducted: (1) constructing the FUEL and determining its content validity and (2) ascertaining its interrater reliability. RESULTS: We found that the FUEL had initial content validity and substantial interrater reliability (Fleiss kappa = .754). CONCLUSION: The FUEL can be a useful clinical and research tool in occupational therapy for the assessment and classification of upper-extremity function for people after stroke. Further studies with larger samples and comparison studies with other similar tools are required to support the tool's reliability and validity. PMID- 26565106 TI - Managing Poststroke Fatigue Using Telehealth: A Case Report. AB - OBJECTIVE: The objective of this study was to examine the effectiveness of delivering Managing Fatigue: A Six-Week Course for Energy Conservation via telehealth for a 70-yr-old man with poststroke fatigue (PSF). METHOD: For this pilot case study, a questionnaire developed by the authors and the Patient Reported Outcomes Measurement Information System Fatigue Short Form 7a were used for screening. The study was implemented via teleconference over an 8-wk period. The Fatigue Impact Scale (FIS) and the Canadian Occupational Performance Measure (COPM) were used to gather pretest and posttest data. RESULTS: After the participant completed the course, decreased fatigue impact was noted on the FIS, and modestly improved occupational performance and satisfaction were evidenced by the COPM. CONCLUSION: For this single participant experiencing PSF, performance and satisfaction on the COPM guardedly improved and fatigue impact decreased after participation in the energy conservation course offered by teleconference, a form of telehealth delivery. Further research is recommended with larger sample sizes. PMID- 26565107 TI - State of the Science: A Roadmap for Research in Sensory Integration. AB - This article builds on the work of Case-Smith and colleagues and proposes a roadmap to guide future research in occupational therapy. To foster best practice in the application of principles and practices of sensory integration (SI), the pillars of practice, advocacy, and education are identified as elements that provide the foundation for research. Each pillar ensures that SI research is conducted in a rigorous and relevant manner. To this end, achievements to date are discussed, with proposed goals presented for each pillar. Finally, the roadmap builds on the pillars and outlines implications for occupational therapy with the overarching theme that a wide array of scientists, educators, therapists, and service recipients will be needed to ensure that those who may benefit most have access to intervention that is evidence based, theory driven, and provided within the highest standards of service delivery. PMID- 26565109 TI - Analytical Aspects of Nanotoxicology. PMID- 26565110 TI - Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction. AB - There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN. PMID- 26565111 TI - Mitophagy in mitosis: More than a myth. PMID- 26565112 TI - Rotationally Commensurate Growth of MoS2 on Epitaxial Graphene. AB - Atomically thin MoS2/graphene heterostructures are promising candidates for nanoelectronic and optoelectronic technologies. Among different graphene substrates, epitaxial graphene (EG) on SiC provides several potential advantages for such heterostructures, including high electronic quality, tunable substrate coupling, wafer-scale processability, and crystalline ordering that can template commensurate growth. Exploiting these attributes, we demonstrate here the thickness-controlled van der Waals epitaxial growth of MoS2 on EG via chemical vapor deposition, giving rise to transfer-free synthesis of a two-dimensional heterostructure with registry between its constituent materials. The rotational commensurability observed between the MoS2 and EG is driven by the energetically favorable alignment of their respective lattices and results in nearly strain free MoS2, as evidenced by synchrotron X-ray scattering and atomic-resolution scanning tunneling microscopy (STM). The electronic nature of the MoS2/EG heterostructure is elucidated with STM and scanning tunneling spectroscopy, which reveals bias-dependent apparent thickness, band bending, and a reduced band gap of ~0.4 eV at the monolayer MoS2 edges. PMID- 26565113 TI - Dynamic Chromatin Regulation from a Single Molecule Perspective. AB - Chromatin regulatory processes, like all biological reactions, are dynamic and stochastic in nature but can give rise to stable and inheritable changes in gene expression patterns. A molecular understanding of those processes is key for fundamental biological insight into gene regulation, epigenetic inheritance, lineage determination, and therapeutic intervention in the case of disease. In recent years, great progress has been made in identifying important molecular players involved in key chromatin regulatory pathways. Conversely, we are only beginning to understand the dynamic interplay between protein effectors, transcription factors, and the chromatin substrate itself. Single-molecule approaches employing both highly defined chromatin substrates in vitro, as well as direct observation of complex regulatory processes in vivo, open new avenues for a molecular view of chromatin regulation. This review highlights recent applications of single-molecule methods and related techniques to investigate fundamental chromatin regulatory processes. PMID- 26565114 TI - Zigzag nanoribbons of two-dimensional silicene-like crystals: magnetic, topological and thermoelectric properties. AB - The effects of electron-electron and spin-orbit interactions on the ground-state magnetic configuration and on the corresponding thermoelectric and spin thermoelectric properties in zigzag nanoribbons of two-dimensional hexagonal crystals are analysed theoretically. The thermoelectric properties of quasi stable magnetic states are also considered. Of particular interest is the influence of Coulomb and spin-orbit interactions on the topological edge states and on the transition between the topological insulator and conventional gap insulator states. It is shown that the interplay of both interactions also has a significant impact on the transport and thermoelectric characteristics of the nanoribbons. The spin-orbit interaction also determines the in-plane magnetic easy axis. The thermoelectric properties of nanoribbons with in-plane magnetic moments are compared to those of nanoribbons with edge magnetic moments oriented perpendicularly to their plane. Nanoribbons with ferromagnetic alignment of the edge moments are shown to reveal spin thermoelectricity in addition to the conventional one. PMID- 26565116 TI - Evolution of a Native Oxide Layer at the a-Si:H/c-Si Interface and Its Influence on a Silicon Heterojunction Solar Cell. AB - The interface microstructure of a silicon heterojunction (SHJ) solar cell was investigated. We found an ultrathin native oxide layer (NOL) with a thickness of several angstroms was formed on the crystalline silicon (c-Si) surface in a very short time (~30 s) after being etched by HF solution. Although the NOL had a loose structure with defects that are detrimental for surface passivation, it acted as a barrier to restrain the epitaxial growth of hydrogenated amorphous silicon (a-Si:H) during the plasma-enhanced chemical vapor deposition (PECVD). The microstructure change of the NOL during the PECVD deposition of a-Si:H layers with different conditions and under different H2 plasma treatments were systemically investigated in detail. When a brief H2 plasma was applied to treat the a-Si:H layer after the PECVD deposition, interstitial oxygen and small-size SiO2 precipitates were transformed to hydrogenated amorphous silicon suboxide alloy (a-SiO(x):H, x ~ 1.5). In the meantime, the interface defect density was reduced by about 50%, and the parameters of the SHJ solar cell were improved due to the post H2 plasma treatment. PMID- 26565115 TI - Nanogel-Conjugated Reverse Transcriptase Inhibitors and Their Combinations as Novel Antiviral Agents with Increased Efficacy against HIV-1 Infection. AB - Nucleoside reverse transcriptase inhibitors (NRTIs) are an integral part of the current antiretroviral therapy (ART), which dramatically reduced the mortality from AIDS and turned the disease from lethal to chronic. The further steps in curing the HIV-1 infection must include more effective targeting of infected cells and virus sanctuaries inside the body and modification of drugs and treatment schedules to reduce common complications of the long-term treatment and increase patient compliancy. Here, we describe novel NRTI prodrugs synthesized from cholesteryl-epsilon-polylysine (CEPL) nanogels by conjugation with NRTI 5' succinate derivatives (sNRTI). Biodegradability, small particle size, and high NRTI loading (30% by weight) of these conjugates; extended drug release, which would allow a weekly administration schedule; high therapeutic index (>1000) with a lower toxicity compared to NRTIs; and efficient accumulation in macrophages known as carriers for HIV-1 infection are among the most attractive properties of new nanodrugs. Nanogel conjugates of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) have been investigated individually and in formulations similar to clinical NRTI cocktails. Nanodrug formulations demonstrated 10-fold suppression of reverse transcriptase activity (EC90) in HIV-infected macrophages at 2-10, 2 4, and 1-2 MUM drug levels, respectively, for single nanodrugs and dual and triple nanodrug cocktails. Nanogel conjugate of lamivudine was the most effective single nanodrug (EC90 2 MUM). Nanodrugs showed a more favorable pharmacokinetics compared to free NRTIs. Infrequent iv injections of PEGylated CEPL-sAZT alone could efficiently suppress HIV-1 RT activity to background level in humanized mouse (hu-PBL) HIV model. PMID- 26565117 TI - 75 years on: a tribute to the contribution of Fuller Albright. PMID- 26565118 TI - The clinical management of acute intracerebral hemorrhage. AB - Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and significant disability among survivors. The management of ICH has been influenced by the results of several major trials completed in the last decade. It is now recognized that hematoma expansion is a major cause of morbidity and mortality. However, efforts to improve clinical outcome through mitigation of hematoma expansion have so far been unsuccessful. Acute blood pressure management has recently been shown to be safe in the setting of acute ICH but there was no reduction in mortality with early blood pressure (BP) lowering. Two large trials of surgical evacuation of supratentorial ICH have not shown improvement in outcome with surgery, thus minimally invasive surgical strategies are currently being studied. Lastly, a better understanding of the pathophysiology of ICH has led to the identification of several new mechanisms of injury that could be potential therapeutic targets. PMID- 26565119 TI - A joint model based on longitudinal CA125 in ovarian cancer to predict recurrence. AB - AIMS: To develop a new package of joint model to fit longitudinal CA125 in epithelial ovarian cancer relapse. PATIENTS & METHODS: Included were 305 epithelial ovarian cancer patients who reached complete remission after cytoreductive surgery and first-line chemotherapy. Univariate and multivariate analysis with a joint model was performed to select independent risk factors, which were subsequently combined to predict recurrence. RESULTS: Independent factors were longitudinal CA125, age, stage and residual tumor size (p < 0.05). Prediction of recurrence with these factors had an average of 80.7% accuracy, 5.6 10.7% better than kinetic factors. CONCLUSION: The new package of joint model fits longitudinal CA125 well. Potential application can be extended to other biomarkers. PMID- 26565120 TI - History of the Concept of Addiction. AB - Our distant forebears wrestled with concepts of alcohol addiction not unlike those of today: Is addiction a sin or a disease? Is addiction caused by the gods, the substance, the individual's vulnerability, or psychological or social factors? Luther, Calvin, and Catholic Church leaders viewed moderate alcohol use as God's gift; used intemperately, it was a moral transgression. The founders of modern scientific psychiatry rejected moral explanations for addiction in favor of an early biological model. The first two versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-I and DSM-II) stigmatized addiction by listing it with other societally disapproved disorders stemming from personality disorder. DSM-III espoused atheoretical, descriptive diagnoses but required tolerance or withdrawal to diagnose dependence. Substance dependence in DSM-III-R included physiological and behavioral symptoms and reflected the substance dependence syndrome. DSM-IV's emphasis on biology in its concept of dependence was unchanged from its immediate predecessors. DSM-5 declared that all drugs taken in excess have in common the direct activation of the brain reward system. This article examines evolving concepts of alcohol addiction through 12,000 years of recorded human history, from the first mention of alcohol consumption in China more than 12,000 years ago to alcohol use and abuse in the DSM era, 1952 to the present. PMID- 26565121 TI - The Role of Craving in Substance Use Disorders: Theoretical and Methodological Issues. AB - Craving is a central feature of addiction. Its recent inclusion as a diagnostic criterion for substance use disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders appears at a time when craving research is at an all-time high. Craving is thought to predict relapse and may deter individuals from even trying to quit. Researchers have developed experimental craving-induction paradigms to identify factors contributing to craving and to test interventions to alleviate craving. This review offers a critique of laboratory craving studies, with particular emphasis on cigarette craving. It raises questions concerning several conceptual and methodological assumptions underlying this research, identifies processes that may explain why cravings are linked to drug use and relapse, addresses contextual factors that may influence various experiences of craving, and considers recent interventions targeting craving. The relation between craving and both emotion and coping is discussed, as well as the level of insight that individuals have about their own future cravings. PMID- 26565122 TI - The Efficacy of Exposure Therapy for Anxiety-Related Disorders and Its Underlying Mechanisms: The Case of OCD and PTSD. AB - In this review we describe the intricate interrelationship among basic research, conceptualization of psychopathology, treatment development, treatment outcome research, and treatment mechanism research and how the interactions among these areas of study further our knowledge about psychopathology and its treatment. In describing the work of Edna Foa and her colleagues in anxiety disorders, we demonstrate how emotional processing theory of anxiety-related disorders and their treatment using exposure therapy have generated hypotheses about the psychopathology of posttraumatic stress disorder and obsessive-compulsive anxiety disorder that have informed the development and refinement of specific treatment protocols for these disorders: prolonged exposure and exposure and response (ritual) prevention. Further, we have shown that the next step after the development of theoretically driven treatment protocols is to evaluate their efficacy. Once evidence for a treatment's efficacy has accumulated, studies of the mechanisms involved in the reduction of the targeted psychopathology are conducted, which in turn inform the theory and further refine the treatments. We conclude our review with a discussion of how the knowledge derived from Foa and colleagues' programmatic research together with knowledge emerging from basic research on extinction learning can inform future research on the psychopathology of anxiety disorders and their treatments. PMID- 26565124 TI - Sobetirome: the past, present and questions about the future. AB - Sobetirome binds selectively to the main hepatic form of thyroid hormone (TH) receptor, TRbeta1, compared to TRalpha1, which is principally responsible for thyrotoxic effects on heart, muscle and bone. Sobetirome also preferentially accumulates in liver. It was originally envisaged that sobetirome could be used to stimulate hepatic pathways that lower cholesterol without harmful side effects and might be used in conjunction with statins. Indeed, sobetirome progressed through preclinical animal studies and Phase I human clinical trials with excellent results and without obvious harmful side effects. Despite the fact that cardiovascular disease remains a major cause of mortality and that new therapies are desperately needed, it is unlikely that sobetirome will progress in further human clinical trials in the near future. The emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant. Further, fears of thyrotoxic effects in the heart and emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, has reduced enthusiasm for this strategy. We argue that it is nevertheless important to explore uses of sobetirome in humans; more treatment strategies would help patients with hard-to-treat dyslipidemias. Sobetirome may also have additional applications in orphan indications and short-term controlled weight loss. PMID- 26565125 TI - Retrospective Analysis of an Ongoing Group-Based Modified Constraint-Induced Movement Therapy Program for Children with Acquired Brain Injury. AB - AIM: A pretest-posttest retrospective design was used to evaluate the impact of a group-based modified constraint-induced movement therapy (mCIMT) program on upper extremity function and occupational performance. METHODS: 20 children ages 3 to 18 years with hemiplegia following an acquired brain injury participated in a 2 week group mCIMT program. Upper extremity function was measured with the Assisting Hand Assessment (AHA) and subtests from the Quality of Upper Extremity Skills Test (QUEST). Occupational performance and satisfaction were assessed using the Canadian Occupational Performance Measure (COPM). Data were analyzed using a Wilcoxon signed-ranks test. RESULTS: Group-based analysis revealed upper extremity function and occupational performance attained statistically significant improvements from pre- to postintervention on all outcome measures (AHA: Z = -3.63, p = <.001; QUEST Grasps: Z = -3.10, p = .002; QUEST Dissociated Movement: Z = -2.51, p = .012; COPM Performance: Z = -3.64, p = <.001; COPM Satisfaction: Z = -3.64, p = <.001). Across individuals, clinically significant improvements were found in 65% of participants' AHA scores. 80% of COPM Performance scores and 70% of COPM Satisfaction scores demonstrated clinically significant improvements in at least one identified goal. CONCLUSIONS: This study is an initial step in evaluating and providing preliminary evidence supporting the effectiveness of a group-based mCIMT program for children with hemiplegia following an acquired brain injury. PMID- 26565126 TI - Role of Multi-Electron Effects in the Asymmetry of Strong-Field Ionization and Fragmentation of Polar Molecules: The Methyl Halide Series. AB - We report angle- and momentum-resolved measurements of the dissociative ionization and Coulomb explosion of methyl halides (CH3F, CH3Cl, CH3Br, and CH3I) in intense phase-controlled two-color laser fields. At moderate laser intensities, we find that the emission asymmetry of low-energy CH3(+) fragments from the CH3(+) + X(+) (X = F, Cl, Br, or I) channel reflects the asymmetry of the highest occupied molecular orbital of the neutral molecule with important contributions from the Stark effect. This asymmetry is correctly predicted by the weak-field asymptotic theory, provided that the Stark effect on the ionization potentials is calculated using a nonperturbative multielectron approach. In the case of high laser intensities, we observe a reversal of the emission asymmetries for high-energy CH3(+) fragments, originating from the dissociation of CH3X(q+) with q >= 2. We propose ionization to electronically excited states to be at the origin of the reversed asymmetries. We also report the measurements of the emission asymmetry of H3(+), which is found to be identical to that of the low energy CH3(+) fragments measured at moderate laser intensities. All observed fragmentation channels are assigned with the help of CCSD(T) calculations. Our results provide a benchmark for theories of strong-field processes and demonstrate the importance of multielectron effects in new aspects of the molecular response to intense laser fields. PMID- 26565127 TI - Electrochemical Imaging and Redox Interrogation of Surface Defects on Operating SrTiO3 Photoelectrodes. AB - We introduce electrochemical imaging and nano-resolved measurements of catalytic intermediates on operating SrTiO3 photoelectrodes. Spatially resolved redox titrations of photogenerated reactive oxygen species (ROS) were used to profile changes in ROS coverage and reactivity at pristine and ion-milled defective areas on n-doped (100) SrTiO3. Adsorbed ROS reached a potential-dependent limiting coverage of ~0.1 monolayer and did not differ significantly between milled and pristine areas. However, the reaction kinetics between a solution-phase mediator and adsorbed ROS were found to be significantly decreased over ion-milled areas. Using a nanoelectrode, we resolved ksi values of 5 and 300 m(3)/s.mol for these bimolecular reactions at defective and pristine sites, respectively. Ion-milled areas also showed significantly decreased activity toward photo-oxidations, providing evidence that photogenerated ROS mediate fast charge-transfer reactions with solution-phase species at the semiconductor-electrolyte interface. Our results provide spatially resolved direct evidence of the impact of surface defects on the performance of photoelectrochemical systems. Scanning electrochemical microscopy offers a powerful method for evaluating the reactivity of an operating electrochemical interface by using redox titrations that detected as few as 30 attomoles of adsorbed ROS. PMID- 26565128 TI - Tracing Stigma in Long-Term Care Insurance in Israel: Stakeholders' Views of Policy Implementation. AB - Almost all developed countries provide some answers for long-term care, but only a few countries in the world, such as Japan, Austria, the Netherlands, Germany, and Israel, have implemented long-term care insurance (LTCI) based on legislation and entitlement principles. In Israel, a community-based LTCI social program has achieved multiple goals and considerably improved the life of frail older people. However, some studies show that despite the rising costs of home care and the mandatory and almost universal nature of LTCI there are still cases in which people with Alzheimer's disease (AD) and other types of dementia or their relatives vacillate or even decline to make use of their rights. We examined the question of whether these patterns may reflect the presence of welfare stigma (i.e., stigmatized views of LTCI) either related to identity stigma of persons with AD or to treatment stigma, usually associated with welfare bureaucracy. Based on a qualitative design, this article uses a methodology of personal in depth and focus group triangulation, by which the views of three groups of stakeholders are explored and compared: persons with AD, relatives, and professionals. Findings showed the presence of stigmatic self-images among persons with AD or other types of dementia and the absence of such images in relatives' and professionals' views of them and of LTCI. However, treatment stigma was found to be primarily associated with eligibility determination procedures. The study concludes that LTCI, even when mandated and almost universal, may also generate welfare stigma due to the ways in which it is implemented. PMID- 26565129 TI - Evaluating Long-term Outcomes of NHS Stop Smoking Services (ELONS): a prospective cohort study. AB - BACKGROUND: NHS Stop Smoking Services (SSSs) provide free at the point of use treatment for smokers who would like to stop. Since their inception in 1999 they have evolved to offer a variety of support options. Given the changes that have happened in the provision of services and the ongoing need for evidence on effectiveness, the Evaluating Long-term Outcomes for NHS Stop Smoking Services (ELONS) study was commissioned. OBJECTIVES: The main aim of the study was to explore the factors that determine longer-term abstinence from smoking following intervention by SSSs. There were also a number of additional objectives. DESIGN: The ELONS study was an observational study with two main stages: secondary analysis of routine data collected by SSSs and a prospective cohort study of service clients. The prospective study had additional elements on client satisfaction, well-being and longer-term nicotine replacement therapy (NRT) use. SETTING: The setting for the study was SSSs in England. For the secondary analysis, routine data from 49 services were obtained. For the prospective study and its added elements, nine services were involved. The target population was clients of these services. PARTICIPANTS: There were 202,804 cases included in secondary analysis and 3075 in the prospective study. INTERVENTIONS: A combination of behavioural support and stop smoking medication delivered by SSS practitioners. MAIN OUTCOME MEASURES: Abstinence from smoking at 4 and 52 weeks after setting a quit date, validated by a carbon monoxide (CO) breath test. RESULTS: Just over 4 in 10 smokers (41%) recruited to the prospective study were biochemically validated as abstinent from smoking at 4 weeks (which was broadly comparable with findings from the secondary analysis of routine service data, where self-reported 4-week quit rates were 48%, falling to 34% when biochemical validation had occurred). At the 1-year follow-up, 8% of prospective study clients were CO validated as abstinent from smoking. Clients who received specialist one-to-one behavioural support were twice as likely to have remained abstinent than those who were seen by a general practitioner (GP) practice and pharmacy providers [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2 to 4.6]. Clients who received group behavioural support (either closed or rolling groups) were three times more likely to stop smoking than those who were seen by a GP practice or pharmacy providers (OR 3.4, 95% CI 1.7 to 6.7). Satisfaction with services was high and well-being at baseline was found to be a predictor of abstinence from smoking at longer-term follow-up. Continued use of NRT at 1 year was rare, but no evidence of harm from longer-term use was identified from the data collected. CONCLUSIONS: Stop Smoking Services in England are effective in helping smokers to move away from tobacco use. Using the 52-week CO-validated quit rate of 8% found in this study, we estimate that in the year 2012-13 the services supported 36,249 clients to become non-smokers for the remainder of their lives. This is a substantial figure and provides one indicator of the ongoing value of the treatment that the services provide. The study raises a number of issues for future research including (1) examining the role of electronic cigarettes (e-cigarettes) in smoking cessation for service clients [this study did not look at e-cigarette use (except briefly in the longer-term NRT study) but this is a priority for future studies]; (2) more detailed comparisons of rolling groups with other forms of behavioural support; (3) further exploration of the role of practitioner knowledge, skills and use of effective behaviour change techniques in supporting service clients to stop smoking; (4) surveillance of the impact of structural and funding changes on the future development and sustainability of SSSs; and (5) more detailed analysis of well-being over time between those who successfully stop smoking and those who relapse. Further research on longer-term use of non-combustible nicotine products that measures a wider array of biomarkers of smoking-related harm such as lung function tests or carcinogen metabolites. FUNDING: The National Institute for Health Research Health Technology Assessment programme. The UK Centre for Tobacco and Alcohol Studies provided funding for the longer-term NRT study. PMID- 26565130 TI - Upper extremity neuro-rehabilitation through the use of power mobility. AB - Power mobility is typically used as an accommodative form of assistive technology allowing individuals with impaired ambulation to remain mobile. While research has focused on the cognitive development and social benefits of power mobility for individuals with developmental disabilities, research is lacking on using this technology to rehabilitate physical dysfunction. Recent technology, such as robot-mediated neuro-rehabilitation, is proving effective in upper extremity rehabilitation, but lacks the movement feedback of power mobility. This article presents a case study of a client with cerebral palsy who experienced severe neural impairment following a motor vehicle accident. As a previous power mobility user, the client identified returning to using power mobility with the affected upper extremity as a key functional goal. This case study describes the series of steps that returned the client to independent mobility and increased upper extremity function. PMID- 26565131 TI - Developing a research agenda for nursing and midwifery: a modified Delphi study. AB - AIM: We sought to ascertain the nursing and midwifery research priorities at a large private tertiary hospital in Australia. DESIGN: A modified Delphi technique with two rounds of questionnaires. METHODS: The first round survey was distributed to 448 nurses and midwives with a 19.2% (n=86) response rate. Due to a low response rate in some specialties, the second round of the Delphi was only sent to nurses in the Learning and Organisational Development speciality who were asked to rank 10 identified topics specific to Learning and Organisational Development using a five point Likert-type scale. RESULTS: Two hundred and fifty seven topics were identified in Round One and were condensed to 181 topics. Each topic was assigned to one of four categories: clinical audit; existing evidence base; research; or other topics which fell beyond the bounds of nursing or midwifery research. Twenty three research topics were identified with priorities focusing on learning and development and workforce issues. CONCLUSION: Priorities were congruent with the organisation's strategic workforce focus. Topics identified in this study will ensure that the nursing and midwifery research conducted at the study setting is relevant and reflects priorities as determined by clinical nurses and midwives. PMID- 26565132 TI - Improving proprioceptive deficits after stroke through robot-assisted training of the upper limb: a pilot case report study. AB - The purpose of this study was to determine whether a conventional robot-assisted therapy of the upper limb was able to improve proprioception and motor recovery of an individual after stroke who exhibited proprioceptive deficits. After robotic sensorimotor training, significant changes were observed in kinematic performance variables. Two quantitative parameters evaluating position sense improved after training. Range of motion during shoulder and wrist flexion improved, but only wrist flexion remained improved at 3-month follow-up. These preliminary results suggest that intensive robot-aided rehabilitation may play an important role in the recovery of sensory function. However, further studies are required to confirm these data. PMID- 26565133 TI - Hospital Ownership of a Postacute Care Facility Influences Discharge Destinations After Emergent Surgery. AB - OBJECTIVE: The aim of the study was to identify hospital characteristics associated with variation in patient disposition after emergent surgery. SUMMARY BACKGROUND DATA: Colon resections in elderly patients are often done in emergent settings. Although these operations are known to be riskier, there are limited data regarding postoperative discharge destination. METHODS: We evaluated Medicare beneficiaries who underwent emergent colectomy between 2008 and 2010. Using hierarchical logistic regression, we estimated patient and hospital-level risk-adjusted rates of nonhome discharges. Hospitals were stratified into quintiles based on their nonhome discharge rates. Generalized linear models were used to identify hospital structural characteristics associated with nonhome discharges (comparing discharge to skilled nursing facilities vs home with/without home health services). RESULTS: Of the 122,604 patients surviving to discharge after emergent colectomy at 3012 hospitals, 46.7% were discharged to a nonhome destination. There was a wide variation in risk and reliability-adjusted nonhome discharge rates across hospitals (15% to 80%). Patients at hospitals in the highest quintile of nonhome discharge rates were more likely to have longer hospitalizations (15.1 vs 13.2; P < 0.001) and more complications (43.2% vs 34%; P < 0.001). On multivariable analysis, only hospital ownership of a skilled nursing facility (P < 0.001), teaching status (P = 0.025), and low nurse-to patient ratios (P = 0.002) were associated with nonhome discharges. CONCLUSIONS: Nearly half of Medicare beneficiaries are discharged to a nonhome destination after emergent colectomy. Hospital ownership of a skilled nursing facility and low nurse-to-patient ratios are highly associated with nonhome discharges. This may signify the underlying financial incentives to preferentially utilize postacute care facilities under the traditional fee-for-service payment model. PMID- 26565135 TI - Best Practices: Targeting Surgeon Communication at the End of Life. PMID- 26565136 TI - Long-term Mortality After Rapid Screening and Decolonization of Staphylococcus Aureus Carriers: Observational Follow-up Study of a Randomized, Placebo controlled Trial. AB - OBJECTIVE: To identify patients who benefit most from Staphylococcus aureus screening and decolonization treatment upon admission. BACKGROUND: S. aureus carriers are at increased risk of developing surgical-site infections with S. aureus. Previously, we demonstrated in a randomized, placebo-controlled trial (RCT) that these infections can largely be prevented by detection of carriage and decolonization treatment upon admission. In this study, we analyzed 1- and 3-year mortality rates in both treatment arms of the RCT to identify patient groups that should be targeted when implementing the screen-and-treat strategy. METHODS: Three years after enrolment in the RCT, mortality dates of all surgical patients were checked. One- and 3-year mortality rates were calculated for all patients and for various subgroups. RESULTS: After 3 years, 44 of 431 (10.2%) and 43 of 362 (11.9%) patients had died in the mupirocin/chlorhexidine and placebo groups, respectively. No significant differences in mortality rates were observed between the treatment groups or the subgroups according to type of surgery. In the subgroup of patients with clean procedures (382 cardiothoracic, 167 orthopedic, 61 vascular, and 56 other), mupirocin/chlorhexidine reduced 1-year mortality: 11 of 365 (3.0%) died in the mupirocin/chlorhexidine versus 21 of 301 (7.0%) in the placebo group [hazard ratio = 0.38 (95% CI: 0.18-0.81)]. CONCLUSIONS: Detection and decolonization of S. aureus carriage not only prevents S. aureus surgical site infections but also reduces 1-year mortality in surgical patients undergoing clean procedures. Such patients with a high risk of developing S. aureus infections should therefore be the primary target when implementing the screen and-treat strategy in clinical practice. PMID- 26565138 TI - Perioperative Fluid Utilization Variability and Association With Outcomes: Considerations for Enhanced Recovery Efforts in Sample US Surgical Populations. AB - OBJECTIVES: To study current perioperative fluid administration and associated outcomes in common surgical cohorts in the United States. BACKGROUND: An element of enhanced recovery care protocols, optimized perioperative fluid administration may be associated with improved outcomes; however, there is currently no consensus in the United States on fluid use or the effects on outcomes of this use. METHODS: The study included all inpatients receiving colon, rectal, or primary hip or knee surgery, 18 years of age or older, who were discharged from a hospital between January 1, 2008 and June, 30 2012 in the Premier Research Database. Patient outcomes and intravenous fluid utilization on the day of surgery were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low day-of-surgery fluids with the likelihood of increased hospital length of stay (LOS), total costs, or postoperative ileus. RESULTS: The study showed significant associations between high fluid volume given on the day of surgery with both increased LOS (odds ratio 1.10-1.40) and increased total costs (odds ratio 1.10-1.50). High fluid utilization was associated with increased presence of postoperative ileus for both rectal and colon surgery patients. Low fluid utilization was also associated with worse outcomes. CONCLUSIONS: According to results from this review of current practice in US hospitals, fluid optimization would likely lead to decreased variability and improved outcomes. PMID- 26565140 TI - Weekday of Esophageal Cancer Surgery and Its Relation to Prognosis. AB - OBJECTIVE: To assess whether weekday of surgery influences long-term survival in esophageal cancer. BACKGROUND: Increased 30-day mortality rates have been reported in patients undergoing elective surgery later compared with earlier in the week. METHODS: This population-based cohort study included 98% of all esophageal cancer patients who underwent elective surgery in Sweden in 1987 to 2010, with follow-up until 2014. The association between weekday of surgery and 5 year all-cause and disease-specific mortality was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, comorbidity, tumor stage, histology, neoadjuvant therapy, and surgeon volume. RESULTS: Among 1748 included patients, surgery conducted from Wednesday to Friday entailed 13% increased all-cause 5 year mortality compared with surgery conducted from Monday to Tuesday (HR = 1.13, 95% CI, 1.01-1.26). The corresponding association was strong for early tumor stages (0-I) (HR = 1.59, 95% CI, 1.17-2.16), moderate for intermediate tumor stage (II) (HR = 1.28, 95% CI, 1.07-1.53), and absent in advanced tumor stages (III-IV) (HR = 0.93, 95% CI, 0.79-1.09). The increase in 5-year mortality for each later weekday (discrete variable) was 7% for all tumor stages (HR = 1.07, 95% CI, 1.02-1.12), 24% for early tumor stages (HR = 1.24, 95% CI, 1.09-1.41), 13% for intermediate stage (HR = 1.13, 95% CI, 1.05-1.22), whereas no increase was found for advanced stages (HR = 0.98, 95% CI, 0.92-1.05). The disease specific 5-year mortality was similar to the all-cause mortality. CONCLUSIONS: The increased 5-year mortality of potentially curable esophageal cancer after surgery later in the week suggests that this surgery is better carried out earlier in the week. PMID- 26565141 TI - A Degenerative/Proinflammatory Intervertebral Disc Organ Culture: An Ex Vivo Model for Anti-inflammatory Drug and Cell Therapy. AB - Resolution of intervertebral disc (IVD) degeneration-associated inflammation is a prerequisite for tissue regeneration and could possibly be achieved by strategies ranging from pharmacological to cell-based therapies. In this study, a proinflammatory disc organ culture model was established. Bovine caudal disc punches were needle punctured and additionally stimulated with lipopolysaccharide (10 MUg/mL) or interleukin-1beta (IL-1beta, 10-100 ng/mL) for 48 h. Two intradiscal therapeutic approaches were tested: (i) a nonsteroidal anti inflammatory drug, diclofenac (Df) and (ii) human mesenchymal stem/stromal cells (MSCs) embedded in an albumin/hyaluronan hydrogel. IL-1beta-treated disc organ cultures showed a statistically significant upregulation of proinflammatory markers (IL-6, IL-8, prostaglandin E2 [PGE2]) and metalloproteases (MMP1, MMP3) expression, while extracellular matrix (ECM) proteins (collagen II, aggrecan) were significantly downregulated. The injection of the anti-inflammatory drug, Df, was able to reduce the levels of proinflammatory cytokines and MMPs and surprisingly increase ECM protein levels. These results point the intradiscal application of anti-inflammatory drugs as promising therapeutics for disc degeneration. In parallel, the immunomodulatory role of MSCs on this model was also evaluated. Although a slight downregulation of IL-6 and IL-8 expression could be found, the variability among the five donors tested was high, suggesting that the beneficial effect of these cells on disc degeneration needs to be further evaluated. The proinflammatory/degenerative IVD organ culture model established can be considered a suitable approach for testing novel therapeutic drugs, thus reducing the number of animals in in vivo experimentation. Moreover, this model can be used to address the cellular and molecular mechanisms that regulate inflammation in the IVD and their implications in tissue degeneration. PMID- 26565142 TI - Chemopreventive role of food-derived proteins and peptides: A review. AB - Cancer is one of the leading causes of mortality and disability worldwide. Although great advances in cancer treatments such as chemotherapy, surgery, and radiation are currently being achieved, their application is associated with numerous and expensive adverse side effects. Epidemiological evidence has demonstrated that the consumption of certain foods potentially prevents up to 35% of cancer cases. Bioactive components are ubiquitous in nature, also in dietary food, providing an essential link in health maintenance, promotion, and prevention of chronic diseases, such as cancer. Development of bioactive proteins and peptides is a current and innovative strategy for cancer prevention/cure. A growing body of anticancer protein and peptides from natural sources has shown the ability to reduce tumor progression through multiple mechanisms including apoptotic, antiproliferative, antiangiogenic, and immunomodulatory activities. This review is focused on proteins and peptides from different food sources including plants, milk, egg, and marine organisms in which chemopreventive properties have been demonstrated. Other aspects such as mechanism of action, bioavailability, and identification and characterization of food-derived peptides by advance separated technologies are also included. This review highlights the potential application of food-derived peptides as functional food ingredients and pharmaceutical candidates in the auxiliary therapy of cancer. PMID- 26565143 TI - Reducing sample size in experiments with animals: historical controls and related strategies. AB - Reducing the number of animal subjects used in biomedical experiments is desirable for ethical and practical reasons. Previous reviews of the benefits of reducing sample sizes have focused on improving experimental designs and methods of statistical analysis, but reducing the size of control groups has been considered rarely. We discuss how the number of current control animals can be reduced, without loss of statistical power, by incorporating information from historical controls, i.e. subjects used as controls in similar previous experiments. Using example data from published reports, we describe how to incorporate information from historical controls under a range of assumptions that might be made in biomedical experiments. Assuming more similarities between historical and current controls yields higher savings and allows the use of smaller current control groups. We conducted simulations, based on typical designs and sample sizes, to quantify how different assumptions about historical controls affect the power of statistical tests. We show that, under our simulation conditions, the number of current control subjects can be reduced by more than half by including historical controls in the analyses. In other experimental scenarios, control groups may be unnecessary. Paying attention to both the function and to the statistical requirements of control groups would result in reducing the total number of animals used in experiments, saving time, effort and money, and bringing research with animals within ethically acceptable bounds. PMID- 26565145 TI - Percolation on a multifractal scale-free planar stochastic lattice and its universality class. AB - We investigate site percolation on a weighted planar stochastic lattice (WPSL), which is a multifractal and whose dual is a scale-free network. Percolation is typically characterized by a threshold value p(c) at which a transition occurs and by a set of critical exponents beta, gamma, nu which describe the critical behavior of the percolation probability P(p), mean cluster size S(p), and the correlation length xi. Besides, the exponent tau characterizes the cluster size distribution function n(s)(p(c)) and the fractal dimension d(f) characterizes the spanning cluster. We numerically obtain the value of p(c) and of all the exponents. These results suggest that the percolation on WPSL belong to a separate universality class than on all other planar lattices. PMID- 26565144 TI - Plasma biomarkers for neuronal ceroid lipofuscinosis. AB - The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative genetic diseases that primarily affect children and have no known cure. A unified clinical rating scale for the juvenile form of NCL has been developed, although it has not been validated in other subtypes and does not give a true measure of the pathophysiological changes occurring during disease progression. In the present study, we have identified candidate biomarkers in blood plasma of NCL disease using multiple proteomic approaches, with the aim of developing a panel of biomarkers that could serve as a metric for therapeutic response. Candidate biomarkers were identified as proteins with levels that significantly differed between patients and controls in both sample sets. The seven candidates identified have previously been associated with neurodegenerative and inflammatory diseases. Multiplex immunoassay based testing was the most efficient and effective evaluation technique and could be employed on a broad scale to track patient response to treatment. PMID- 26565146 TI - Crossing probability for directed polymers in random media. AB - We study the probability that two directed polymers in the same random potential do not intersect. We use the replica method to map the problem onto the attractive Lieb-Liniger model with generalized statistics between particles. Employing both the nested Bethe ansatz and known formula from MacDonald processes, we obtain analytical expressions for the first few moments of this probability and compare them to a numerical simulation of a discrete model at high temperature. From these observations, several large time properties of the noncrossing probabilities are conjectured. Extensions of our formalism to more general observables are discussed. PMID- 26565147 TI - Eigenstate thermalization in systems with spontaneously broken symmetry. AB - A strongly nonintegrable system is expected to satisfy the eigenstate thermalization hypothesis, which states that the expectation value of an observable in an energy eigenstate is the same as the thermal value. This must be revised if the observable is an order parameter for a spontaneously broken symmetry, which has multiple thermal values. We propose that in this case the system is unstable towards forming nearby eigenstates which yield each of the allowed thermal values. We provide strong evidence for this from a numerical study of the two-dimensional transverse-field quantum Ising model. PMID- 26565148 TI - Anisotropy of weakly vibrated granular flows. AB - We experimentally probe the anisotropy of weakly vibrated flowing granular media. Depending on the driving parameters-flow rate and vibration strength-this anisotropy varies significantly. We show how the anisotropy collapses when plotted as a function of the driving stresses, uncovering a direct link between stresses and anisotropy. Moreover, our data suggest that for small anisotropies, the shear stresses vanish. Anisotropy of the fabric of granular media thus plays a crucial role in determining the rheology of granular flows. PMID- 26565149 TI - Using dislocations to probe surface reconstruction in thick freely suspended liquid crystalline films. AB - Surface interactions can cause freely suspended thin liquid crystalline films to form phases different from the bulk material, but it is not known what happens at the surface of thick films. Edge dislocations can be used as a marker for the boundary between the bulk center and the reconstructed surface. We use noncontact mode atomic force microscopy to determine the depth of edge dislocations below the surface of freely suspended thick films of 4-n-heptyloxybenzylidene-4-n heptylaniline (7O.7) in the crystalline B phase. Here, 3.0+/-0.1 nm high steps are found with a width that varies with temperature between 56 and 59 degrees C. Using a strain model for the profile of liquid crystalline layers above an edge dislocation to estimate the depth of the dislocation, we find that the number of reconstructed surface layers increases from 4 to 50 layers as the temperature decreases from 59 to 56 degrees C. This trend tracks the behavior of the phase boundary in the thickness dependent phase diagram of freely suspended films of 7O.7, suggesting that the surface may be reconstructed into a smectic F region. PMID- 26565150 TI - Reconciling transport models across scales: The role of volume exclusion. AB - Diffusive transport is a universal phenomenon, throughout both biological and physical sciences, and models of diffusion are routinely used to interrogate diffusion-driven processes. However, most models neglect to take into account the role of volume exclusion, which can significantly alter diffusive transport, particularly within biological systems where the diffusing particles might occupy a significant fraction of the available space. In this work we use a random walk approach to provide a means to reconcile models that incorporate crowding effects on different spatial scales. Our work demonstrates that coarse-grained models incorporating simplified descriptions of excluded volume can be used in many circumstances, but that care must be taken in pushing the coarse-graining process too far. PMID- 26565151 TI - Rheology of the cytoskeleton as a fractal network. AB - We model the cytoskeleton as a fractal network by identifying each segment with a simple Kelvin-Voigt element with a well defined equilibrium length. The final structure retains the elastic characteristics of a solid or a gel, which may support stress, without relaxing. By considering a very simple regular self similar structure of segments in series and in parallel, in one, two, or three dimensions, we are able to express the viscoelasticity of the network as an effective generalized Kelvin-Voigt model with a power law spectrum of retardation times L~tau(alpha). We relate the parameter alpha with the fractal dimension of the gel. In some regimes (00,sigma->infinity at nonzero and finite sigmaV(c), connects our highest-resolution results with known exact results for monodisperse rods in a continuum. We also compare the pressure profiles obtained from density functionals with the average microscopic pressure profiles derived from the pair distribution function. PMID- 26565174 TI - Exchange fluctuation theorem for correlated quantum systems. AB - We extend the exchange fluctuation theorem for energy exchange between thermal quantum systems beyond the assumption of molecular chaos, and describe the nonequilibrium exchange dynamics of correlated quantum states. The relation quantifies how the tendency for systems to equilibrate is modified in high correlation environments. In addition, a more abstract approach leads us to a "correlation fluctuation theorem". Our results elucidate the role of measurement disturbance for such scenarios. We show a simple application by finding a semiclassical maximum work theorem in the presence of correlations. We also present a toy example of qubit-qudit heat exchange, and find that non-classical behaviour such as deterministic energy transfer and anomalous heat flow are reflected in our exchange fluctuation theorem. PMID- 26565175 TI - Small-scale properties of a stochastic cubic-autocatalytic reaction-diffusion model. AB - We investigate the small-scale properties of a stochastic cubic-autocatalytic reaction-diffusion (CARD) model using renormalization techniques. We renormalize noise-induced ultraviolet divergences and obtain beta functions for the decay rate and coupling at one loop. Assuming colored (power-law) noise, our results show that the behavior of both decay rate and coupling with scale depends crucially on the noise exponent. Interpreting the CARD model as a proxy for a (very simple) living system, our results suggest that power-law correlations in environmental fluctuations can both decrease or increase the growth of structures at smaller scales. PMID- 26565176 TI - Dynamics of the transverse Ising model with next-nearest-neighbor interactions. AB - We study the effects of next-nearest-neighbor (NNN) interactions on the dynamics of the one-dimensional spin-1/2 transverse Ising model in the high-temperature limit. We use exact diagonalization to obtain the time-dependent transverse correlation function and the corresponding spectral density for a tagged spin. Our results for chains of 13 spins with periodic boundary conditions produce results which are valid in the infinite-size limit. In general we find that the NNN coupling produces slower dynamics accompanied by an enhancement of the central mode behavior. Even in the case of a strong transverse field, if the NNN coupling is sufficiently large, then there is a crossover from collective mode to central mode behavior. We also obtain several recurrants for the continued fraction representation of the relaxation function. PMID- 26565177 TI - Clique percolation in random graphs. AB - As a generation of the classical percolation, clique percolation focuses on the connection of cliques in a graph, where the connection of two k cliques means that they share at least l1 makes a step-function-like discontinuous phase transition in the thermodynamic limit and a continuous phase transition for l=1. More interesting, our analysis shows that at the critical point, the order parameter phi(c) for l>1 is neither 0 nor 1, but a constant depending on k and l. All these theoretical findings are in agreement with the simulation results, which give theoretical support and clarification for previous simulation studies of clique percolation. PMID- 26565178 TI - Distributed-order diffusion equations and multifractality: Models and solutions. AB - We study distributed-order time fractional diffusion equations characterized by multifractal memory kernels, in contrast to the simple power-law kernel of common time fractional diffusion equations. Based on the physical approach to anomalous diffusion provided by the seminal Scher-Montroll-Weiss continuous time random walk, we analyze both natural and modified-form distributed-order time fractional diffusion equations and compare the two approaches. The mean squared displacement is obtained and its limiting behavior analyzed. We derive the connection between the Wiener process, described by the conventional Langevin equation and the dynamics encoded by the distributed-order time fractional diffusion equation in terms of a generalized subordination of time. A detailed analysis of the multifractal properties of distributed-order diffusion equations is provided. PMID- 26565179 TI - Monte Carlo study of anisotropic scaling generated by disorder. AB - We analyze the critical properties of the three-dimensional Ising model with linear parallel extended defects. Such a form of disorder produces two distinct correlation lengths, a parallel correlation length xi(?) in the direction along defects and a perpendicular correlation length xi(?) in the direction perpendicular to the lines. Both xi(?) and xi(?) diverge algebraically in the vicinity of the critical point, but the corresponding critical exponents nu(?) and nu(?) take different values. This property is specific for anisotropic scaling and the ratio nu(?)/nu(?) defines the anisotropy exponent theta. Until now, estimates of quantitative characteristics of the critical behavior for such systems have been obtained only within the renormalization group approach. We report a study of the anisotropic scaling in this system via Monte Carlo simulation of the three-dimensional system with Ising spins and nonmagnetic impurities arranged into randomly distributed parallel lines. Several independent estimates for the anisotropy exponent theta of the system are obtained, as well as an estimate of the susceptibility exponent gamma. Our results corroborate the renormalization group predictions obtained earlier. PMID- 26565180 TI - Flocking with discrete symmetry: The two-dimensional active Ising model. AB - We study in detail the active Ising model, a stochastic lattice gas where collective motion emerges from the spontaneous breaking of a discrete symmetry. On a two-dimensional lattice, active particles undergo a diffusion biased in one of two possible directions (left and right) and align ferromagnetically their direction of motion, hence yielding a minimal flocking model with discrete rotational symmetry. We show that the transition to collective motion amounts in this model to a bona fide liquid-gas phase transition in the canonical ensemble. The phase diagram in the density-velocity parameter plane has a critical point at zero velocity which belongs to the Ising universality class. In the density temperature "canonical" ensemble, the usual critical point of the equilibrium liquid-gas transition is sent to infinite density because the different symmetries between liquid and gas phases preclude a supercritical region. We build a continuum theory which reproduces qualitatively the behavior of the microscopic model. In particular, we predict analytically the shapes of the phase diagrams in the vicinity of the critical points, the binodal and spinodal densities at coexistence, and the speeds and shapes of the phase-separated profiles. PMID- 26565181 TI - Statistical analysis of loopy belief propagation in random fields. AB - Loopy belief propagation (LBP), which is equivalent to the Bethe approximation in statistical mechanics, is a message-passing-type inference method that is widely used to analyze systems based on Markov random fields (MRFs). In this paper, we propose a message-passing-type method to analytically evaluate the quenched average of LBP in random fields by using the replica cluster variation method. The proposed analytical method is applicable to general pairwise MRFs with random fields whose distributions differ from each other and can give the quenched averages of the Bethe free energies over random fields, which are consistent with numerical results. The order of its computational cost is equivalent to that of standard LBP. In the latter part of this paper, we describe the application of the proposed method to Bayesian image restoration, in which we observed that our theoretical results are in good agreement with the numerical results for natural images. PMID- 26565182 TI - Role of trapping and crowding as sources of negative differential mobility. AB - Increasing the crowding in an environment does not necessarily trigger negative differential mobility of strongly pushed particles. Moreover, the choice of the model, in particular the kind of microscopic jump rates, may be very relevant in determining the mobility. We support these points via simple examples and we therefore address recent claims saying that crowding in an environment is likely to promote negative differential mobility. Trapping of tagged particles enhanced by increasing the force remains the mechanism determining a drift velocity not monotonous in the driving force. PMID- 26565183 TI - First-passage times for pattern formation in nonlocal partial differential equations. AB - We describe the lifetimes associated with the stochastic evolution from an unstable uniform state to a patterned one when the time evolution of the field is controlled by a nonlocal Fisher equation. A small noise is added to the evolution equation to define the lifetimes and to calculate the mean first-passage time of the stochastic field through a given threshold value, before the patterned steady state is reached. In order to obtain analytical results we introduce a stochastic multiscale perturbation expansion. This multiscale expansion can also be used to tackle multiplicative stochastic partial differential equations. A critical slowing down is predicted for the marginal case when the Fourier phase of the unstable initial condition is null. We carry out Monte Carlo simulations to show the agreement with our theoretical predictions. Analytic results for the bifurcation point and asymptotic analysis of traveling wave-front solutions are included to get insight into the noise-induced transition phenomena mediated by invading fronts. PMID- 26565184 TI - Performance limits of multilevel and multipartite quantum heat machines. AB - We present the general theory of a quantum heat machine based on an N-level system (working medium) whose N-1 excited levels are degenerate, a prerequisite for steady-state interlevel coherence. Our goal is to find out the extent to which coherence in the working medium is an asset for heat machines. The performance bounds of such a machine are common to (reciprocating) cycles that consist of consecutive strokes and continuous cycles wherein the periodically driven system is constantly coupled to cold and hot heat baths. Intriguingly, we find that the machine's performance strongly depends on the relative orientations of the transition-dipole vectors in the system. Perfectly aligned (parallel) transition dipoles allow for steady-state coherence effects, but also give rise to dark states, which hinder steady-state thermalization and thus reduce the machine's performance. Similar thermodynamic properties hold for N two-level atoms conforming to the Dicke model. We conclude that level degeneracy, but not necessarily coherence, is a thermodynamic resource, equally enhancing the heat currents and the power output of the heat machine. By contrast, the efficiency remains unaltered by this degeneracy and adheres to the Carnot bound. PMID- 26565185 TI - Linear-noise approximation and the chemical master equation agree up to second order moments for a class of chemical systems. AB - It is well known that the linear-noise approximation (LNA) agrees with the chemical master equation, up to second-order moments, for chemical systems composed of zero and first-order reactions. Here we show that this is also a property of the LNA for a subset of chemical systems with second-order reactions. This agreement is independent of the number of interacting molecules. PMID- 26565186 TI - Disentangling geometric and dissipative origins of negative Casimir entropies. AB - Dissipative electromagnetic response and scattering geometry are potential sources for the appearance of a negative Casimir entropy. We show that the dissipative contribution familiar from the plane-plane geometry appears also in the plane-sphere and the sphere-sphere geometries and adds to the negative Casimir entropy known to exist in these geometries even for perfectly reflecting objects. Taking the sphere-sphere geometry as an example, we carry out a scattering-channel analysis, which allows us to distinguish between the contributions of different polarizations. We demonstrate that dissipation and geometry share a common feature making possible negative values of the Casimir entropy. In both cases there exists a scattering channel whose contribution to the Casimir free energy vanishes in the high-temperature limit. While the mode mixing channel is associated with the geometric origin, the transverse electric channel is associated with the dissipative origin of the negative Casimir entropy. By going beyond the Rayleigh limit, we find even for large distances that negative Casimir entropies can occur also for Drude-type metals provided the dissipation strength is sufficiently small. PMID- 26565187 TI - Thermodynamic universality of quantum Carnot engines. AB - The Carnot statement of the second law of thermodynamics poses an upper limit on the efficiency of all heat engines. Recently, it has been studied whether generic quantum features such as coherence and quantum entanglement could allow for quantum devices with efficiencies larger than the Carnot efficiency. The present study shows that this is not permitted by the laws of thermodynamics-independent of the model. We will show that rather the definition of heat has to be modified to account for the thermodynamic cost of maintaining non-Gibbsian equilibrium states. Our theoretical findings are illustrated for two experimentally relevant examples. PMID- 26565188 TI - Phase transitions and critical phenomena in the two-dimensional Ising model with dipole interactions: A short-time dynamics study. AB - The ferromagnetic Ising model with antiferromagnetic dipole interactions is investigated by means of Monte Carlo simulations, focusing on the characterization of the phase transitions between the tetragonal liquid and stripe of width h phases. The dynamic evolution of the physical observables is analyzed within the short-time regime for 0.5<=delta<=1.3, where delta is the ratio between the short-range exchange and the long-range dipole interaction constants. The obtained results for the interval 0.5<=delta<=1.2 indicate that the phase transition line between the h=1 stripe and tetragonal liquid phases is continuous. This finding contributes to clarifying the controversy about the order of this transition. This controversy arises from the difficulties introduced in the simulations due to the presence of long-range dipole interactions, such as an important increase in the simulation times that limits the system size used, strong finite size effects, as well as to the existence of multiple metastable states at low temperatures. The study of the short-time dynamics of the model allows us to avoid these hindrances. Moreover, due to the fact that the finite-size effects do not significantly affect the power-law behavior exhibited in the observables within the short-time regime, the results could be attributed to those corresponding to the thermodynamic limit. As a consequence of this, a careful characterization of the critical behavior for the whole transition line is performed by giving the complete set of critical exponents. PMID- 26565189 TI - Nonequilibrium interfacial tension during relaxation. AB - The concept of a nonequilibrium interfacial tension, defined via the work required to deform a system such that the interfacial area is changed while the volume is conserved, is investigated theoretically in the context of the relaxation of an initial perturbation of a colloidal fluid towards the equilibrium state. The corresponding general formalism is derived for systems with planar symmetry and applied to fluid models of colloidal suspensions and polymer solutions. It is shown that the nonequilibrium interfacial tension is not necessarily positive, that negative nonequilibrium interfacial tensions are consistent with strictly positive equilibrium interfacial tensions, and that the sign of the interfacial tension can influence the morphology of density perturbations during relaxation. PMID- 26565190 TI - Quasi-steady-state analysis of coupled flashing ratchets. AB - We perform a quasi-steady-state (QSS) reduction of a flashing ratchet to obtain a Brownian particle in an effective potential. The resulting system is analytically tractable and yet preserves essential dynamical features of the full model. We first use the QSS reduction to derive an explicit expression for the velocity of a simple two-state flashing ratchet. In particular, we determine the relationship between perturbations from detailed balance, which are encoded in the transitions rates of the flashing ratchet, and a tilted-periodic potential. We then perform a QSS analysis of a pair of elastically coupled flashing ratchets, which reduces to a Brownian particle moving in a two-dimensional vector field. We suggest that the fixed points of this vector field accurately approximate the metastable spatial locations of the coupled ratchets, which are, in general, impossible to identify from the full system. PMID- 26565191 TI - Free-energy landscape and nucleation pathway of polymorphic minerals from solution in a Potts lattice-gas model. AB - Metastable minerals commonly form during reactions between water and rock. The nucleation mechanism of polymorphic phases from solution are explored here using a two-dimensional Potts model. The model system is composed of a solvent and three polymorphic solid phases. The local state and position of the solid phase are updated by Metropolis dynamics. Below the critical temperature, a large cluster of the least stable solid phase initially forms in the solution before transitioning into more-stable phases following the Ostwald step rule. The free energy landscape as a function of the modal abundance of each solid phase clearly reveals that before cluster formation, the least stable phase has an energetic advantage because of its low interfacial energy with the solution, and after cluster formation, phase transformation occurs along the valley of the free energy landscape, which contains several minima for the regions of three phases. Our results indicate that the solid-solid and solid-liquid interfacial energy contribute to the formation of the complex free-energy landscape and nucleation pathways following the Ostwald step rule. PMID- 26565192 TI - Conditions for predicting quasistationary states by rearrangement formula. AB - Predicting the long-lasting quasistationary state for a given initial state is one of central issues in Hamiltonian systems having long-range interaction. A recently proposed method is based on the Vlasov description and uniformly redistributes the initial distribution along contours of the asymptotic effective Hamiltonian, which is defined by the obtained quasistationary state and is determined self-consistently. The method, to which we refer as the rearrangement formula, was suggested to give precise prediction under limited situations. Restricting initial states consisting of a spatially homogeneous part and small perturbation, we numerically reveal two conditions that the rearrangement formula prefers: One is a no Landau damping condition for the unperturbed homogeneous part, and the other comes from the Casimir invariants. Mechanisms of these conditions are discussed. Clarifying these conditions, we validate to use the rearrangement formula as the response theory for an external field, and we shed light on improving the theory as a nonequilibrium statistical mechanics. PMID- 26565193 TI - Fluctuating currents in stochastic thermodynamics. I. Gauge invariance of asymptotic statistics. AB - Stochastic thermodynamics uses Markovian jump processes to model random transitions between observable mesoscopic states. Physical currents are obtained from antisymmetric jump observables defined on the edges of the graph representing the network of states. The asymptotic statistics of such currents are characterized by scaled cumulants. In the present work, we use the algebraic and topological structure of Markovian models to prove a gauge invariance of the scaled cumulant-generating function. Exploiting this invariance yields an efficient algorithm for practical calculations of asymptotic averages and correlation integrals. We discuss how our approach generalizes the Schnakenberg decomposition of the average entropy-production rate, and how it unifies previous work. The application of our results to concrete models is presented in an accompanying publication. PMID- 26565194 TI - Fluctuating currents in stochastic thermodynamics. II. Energy conversion and nonequilibrium response in kinesin models. AB - Unlike macroscopic engines, the molecular machinery of living cells is strongly affected by fluctuations. Stochastic thermodynamics uses Markovian jump processes to model the random transitions between the chemical and configurational states of these biological macromolecules. A recently developed theoretical framework [A. Wachtel, J. Vollmer, and B. Altaner, Phys. Rev. E 92, 042132 (2015)] provides a simple algorithm for the determination of macroscopic currents and correlation integrals of arbitrary fluctuating currents. Here we use it to discuss energy conversion and nonequilibrium response in different models for the molecular motor kinesin. Methodologically, our results demonstrate the effectiveness of the algorithm in dealing with parameter-dependent stochastic models. For the concrete biophysical problem our results reveal two interesting features in experimentally accessible parameter regions: the validity of a nonequilibrium Green-Kubo relation at mechanical stalling as well as a negative differential mobility for superstalling forces. PMID- 26565195 TI - Screening like charges in one-dimensional Coulomb systems: Exact results. AB - The possibility that like charges can attract each other under the mediation of mobile counterions is by now well documented experimentally, numerically, and analytically. Yet, obtaining exact results is in general impossible, or restricted to some limiting cases. We work out here in detail a one-dimensional model that retains the essence of the phenomena present in higher-dimensional systems. The partition function is obtained explicitly, from which a wealth of relevant quantities follow, such as the effective force between the charges or the counterion profile in their vicinity. Isobaric and canonical ensembles are distinguished. The case of two equal charges screened by an arbitrary number N of counterions is first studied, before the more general asymmetric situation is addressed. It is shown that the parity of N plays a key role in the long-range physics. PMID- 26565196 TI - Avalanche-size distributions in mean-field plastic yielding models. AB - We discuss the size distribution N(S) of avalanches occurring at the yielding transition of mean-field (i.e., Hebraud-Lequeux) models of amorphous solids. The size distribution follows a power law dependence of the form N(S)~S(-tau). However (contrary to what is found in its depinning counterpart), the value of tau depends on details of the dynamic protocol used. For random triggering of avalanches we recover the tau=3/2 exponent typical of mean-field models, which, in particular, is valid for the depinning case. However, for the physically relevant case of external loading through a quasistatic increase of applied strain, a smaller exponent (close to 1) is obtained. This result is rationalized by mapping the problem to an effective random walk in the presence of a moving absorbing boundary. PMID- 26565197 TI - Deviation from the Maxwell-Cattaneo law: Role of asymmetric interparticle interactions. AB - Nonstationary heat conduction in a few one-dimensional nonlinear lattices is studied numerically based on the Maxwell-Cattaneo (MC) law. We simulate the relaxation process and calculate the magnitudes of the temperature oscillation A(T)(t) and the local heat current oscillation A(j)(t). A phase difference between A(T)(t) and A(j)(t) is observed, which not only verifies the existence of the time lag tau in the MC law but also provides a better way of determining the critical wavelength L(*) that separates between oscillatory and diffusive relaxation modes. However, clear deviations from the MC law are observed. Not only do the decay exponents differ from the theoretical expectations, but, more importantly, suboscillation in the diffusive regime, which is not expected by the MC law, is found in the lattices with asymmetric interactions as well. These findings imply that higher-order effects must be considered in order to well describe the nonstationary heat conduction process in these systems. PMID- 26565198 TI - Sample-dependent first-passage-time distribution in a disordered medium. AB - Above two dimensions, diffusion of a particle in a medium with quenched random traps is believed to be well described by the annealed continuous-time random walk. We propose an approximate expression for the first-passage-time (FPT) distribution in a given sample that enables detailed comparison of the two problems. For a system of finite size, the number and spatial arrangement of deep traps yield significant sample-to-sample variations in the FPT statistics. Numerical simulations of a quenched trap model with power-law sojourn times confirm the existence of two characteristic time scales and a non-self-averaging FPT distribution, as predicted by our theory. PMID- 26565199 TI - Relating Granger causality to long-term causal effects. AB - In estimation of causal couplings between observed processes, it is important to characterize coupling roles at various time scales. The widely used Granger causality reflects short-term effects: it shows how strongly perturbations of a current state of one process affect near future states of another process, and it quantifies that via prediction improvement (PI) in autoregressive models. However, it is often more important to evaluate the effects of coupling on long term statistics, e.g., to find out how strongly the presence of coupling changes the variance of a driven process as compared to an uncoupled case. No general relationships between Granger causality and such long-term effects are known. Here, we pose the problem of relating these two types of coupling characteristics, and we solve it for a class of stochastic systems. Namely, for overdamped linear oscillators, we rigorously derive that the above long-term effect is proportional to the short-term effects, with the proportionality coefficient depending on the prediction interval and relaxation times. We reveal that this coefficient is typically considerably greater than unity so that small normalized PI values may well correspond to quite large long-term effects of coupling. The applicability of the derived relationship to wider classes of systems, its limitations, and its value for further research are discussed. To give a real-world example, we analyze couplings between large-scale climatic processes related to sea surface temperature variations in equatorial Pacific and North Atlantic regions. PMID- 26565200 TI - Data-driven coarse graining in action: Modeling and prediction of complex systems. AB - In many physical, technological, social, and economic applications, one is commonly faced with the task of estimating statistical properties, such as mean first passage times of a temporal continuous process, from empirical data (experimental observations). Typically, however, an accurate and reliable estimation of such properties directly from the data alone is not possible as the time series is often too short, or the particular phenomenon of interest is only rarely observed. We propose here a theoretical-computational framework which provides us with a systematic and rational estimation of statistical quantities of a given temporal process, such as waiting times between subsequent bursts of activity in intermittent signals. Our framework is illustrated with applications from real-world data sets, ranging from marine biology to paleoclimatic data. PMID- 26565201 TI - Relaxation dynamics in the presence of pulse multiplicative noise sources with different correlation properties. AB - The relaxation dynamics of a system described by a Langevin equation with pulse multiplicative noise sources with different correlation properties is considered. The solution of the corresponding Fokker-Planck equation is derived for Gaussian white noise. Moreover, two pulse processes with regulated periodicity are considered as a noise source: the dead-time-distorted Poisson process and the process with fixed time intervals, which is characterized by an infinite correlation time. We find that the steady state of the system is dependent on the correlation properties of the pulse noise. An increase of the noise correlation causes the decrease of the mean value of the solution at the steady state. The analytical results are in good agreement with the numerical ones. PMID- 26565202 TI - Comparison between Smoluchowski and Boltzmann approaches for self-propelled rods. AB - Considering systems of self-propelled polar particles with nematic interactions ("rods"), we compare the continuum equations describing the evolution of polar and nematic order parameters, derived either from Smoluchowski or Boltzmann equations. Our main goal is to understand the discrepancies between the continuum equations obtained so far in both frameworks. We first show that, in the simple case of point-like particles with only alignment interactions, the continuum equations obtained have the same structure in both cases. We further study, in the Smoluchowski framework, the case where an interaction force is added on top of the aligning torque. This clarifies the origin of the additional terms obtained in previous works. Our observations lead us to emphasize the need for a more involved closure scheme than the standard normal form of the distribution when dealing with active systems. PMID- 26565203 TI - Confinement effects upon the separation of structural transitions in linear systems with restricted bond fluctuation ranges. AB - By means of advanced parallel replica-exchange Monte Carlo methods we examine the influence of elasticity and confinement on the structural transitions of linear systems with restricted bonded interaction. For this purpose, we adopt a model for coarse-grained flexible polymers of finite length in the dilute regime. Hyperphase diagrams are constructed using energy-dependent canonical quantities to demonstrate the effects of the changes in the range of the confined interaction on the liquid and solid structural phases. With increasing bonded interaction range we observe the disappearance of the liquid phase and the fusion of the gas-liquid (or Theta) and the liquid-solid transitions. One of the most remarkable features, the liquid-gas transition, changes from second to first order if the confined interaction range exceeds a threshold that separates polymeric from nonpolymeric systems. The notoriously difficult sampling of the entropically suppressed conformations in the region of very strong first-order transitions is improved by using multiple Gaussian modified ensembles. PMID- 26565204 TI - Relaxation times of dissipative many-body quantum systems. AB - We study relaxation times, also called mixing times, of quantum many-body systems described by a Lindblad master equation. We in particular study the scaling of the spectral gap with the system length, the so-called dynamical exponent, identifying a number of transitions in the scaling. For systems with bulk dissipation we generically observe different scaling for small and for strong dissipation strength, with a critical transition strength going to zero in the thermodynamic limit. We also study a related phase transition in the largest decay mode. For systems with only boundary dissipation we show a generic bound that the gap cannot be larger than ~1/L. In integrable systems with boundary dissipation one typically observes scaling of ~1/L(3), while in chaotic ones one can have faster relaxation with the gap scaling as ~1/L and thus saturating the generic bound. We also observe transition from exponential to algebraic gap in systems with localized modes. PMID- 26565205 TI - Exact satisfiability threshold for k-satisfiability problems on a Bethe lattice. AB - The satisfiability threshold for constraint satisfaction problems is that value of the ratio of constraints (or clauses) to variables, above which the probability that a random instance of the problem has a solution is zero in the large system limit. Two different approaches to obtaining this threshold have been discussed in the literature: using first or second moment methods which give rigorous bounds or using the nonrigorous but powerful replica-symmetry-breaking (RSB) approach, which gives very accurate predictions on random graphs. In this paper, we lay out a different route to obtaining this threshold on a Bethe lattice. We need make no assumptions about the solution-space structure, a key assumption in the RSB approach. Despite this, our expressions and threshold values exactly match the best predictions of the cavity method under the one-step RSB hypothesis. In addition we can use the same procedure to obtain other useful quantities on the Bethe lattice such as the second moment of the number of solutions. Our method hence provides alternate interpretations as well as motivations for the key equations in the RSB approach. PMID- 26565206 TI - Stability and anomalous entropic elasticity of subisostatic random-bond networks. AB - We study the elasticity of thermalized spring networks under an applied bulk strain. The networks considered are subisostatic random-bond networks that, in the athermal limit, are known to have vanishing bulk and linear shear moduli at zero bulk strain. Above a bulk strain threshold, however, these networks become rigid, although surprisingly the shear modulus remains zero until a second, higher, strain threshold. We find that thermal fluctuations stabilize all networks below the rigidity transition, resulting in systems with both finite bulk and shear moduli. Our results show a T(0.66) temperature dependence of the moduli in the region below the bulk strain threshold, resulting in networks with anomalously high rigidity as compared to ordinary entropic elasticity. Furthermore, we find a second regime of anomalous temperature scaling for the shear modulus at its zero-temperature rigidity point, where it scales as T(0.5), behavior that is absent for the bulk modulus since its athermal rigidity transition is discontinuous. PMID- 26565207 TI - Dynamical class of a two-dimensional plasmonic Dirac system. AB - A current goal in plasmonic science and technology is to figure out how to manage the relaxational dynamics of surface plasmons in graphene since its damping constitutes a hinder for the realization of graphene-based plasmonic devices. In this sense we believe it might be of interest to enlarge the knowledge on the dynamical class of two-dimensional plasmonic Dirac systems. According to the recurrence relations method, different systems are said to be dynamically equivalent if they have identical relaxation functions at all times, and such commonality may lead to deep connections between seemingly unrelated physical systems. We employ the recurrence relations approach to obtain relaxation and memory functions of density fluctuations and show that a two-dimensional plasmonic Dirac system at long wavelength and zero temperature belongs to the same dynamical class of standard two-dimensional electron gas and classical harmonic oscillator chain with an impurity mass. PMID- 26565208 TI - Most energetic passive states. AB - Passive states are defined as those states that do not allow for work extraction in a cyclic (unitary) process. Within the set of passive states, thermal states are the most stable ones: they maximize the entropy for a given energy, and similarly they minimize the energy for a given entropy. Here we find the passive states lying in the other extreme, i.e., those that maximize the energy for a given entropy, which we show also minimize the entropy when the energy is fixed. These extremal properties make these states useful to obtain fundamental bounds for the thermodynamics of finite-dimensional quantum systems, which we show in several scenarios. PMID- 26565209 TI - Shortcuts to adiabaticity from linear response theory. AB - A shortcut to adiabaticity is a finite-time process that produces the same final state as would result from infinitely slow driving. We show that such shortcuts can be found for weak perturbations from linear response theory. With the help of phenomenological response functions, a simple expression for the excess work is found-quantifying the nonequilibrium excitations. For two specific examples, i.e., the quantum parametric oscillator and the spin 1/2 in a time-dependent magnetic field, we show that finite-time zeros of the excess work indicate the existence of shortcuts. Finally, we propose a degenerate family of protocols, which facilitates shortcuts to adiabaticity for specific and very short driving times. PMID- 26565210 TI - Stationary properties of maximum-entropy random walks. AB - Maximum-entropy (ME) inference of state probabilities using state-dependent constraints is popular in the study of complex systems. In stochastic systems, how state space topology and path-dependent constraints affect ME-inferred state probabilities remains unknown. To that end, we derive the transition probabilities and the stationary distribution of a maximum path entropy Markov process subject to state- and path-dependent constraints. A main finding is that the stationary distribution over states differs significantly from the Boltzmann distribution and reflects a competition between path multiplicity and imposed constraints. We illustrate our results with particle diffusion on a two dimensional landscape. Connections with the path integral approach to diffusion are discussed. PMID- 26565211 TI - Full distribution of work done on a quantum system for arbitrary initial states. AB - We propose an approach to define and measure the statistics of work, internal energy and dissipated heat in a driven quantum system. In our framework the presence of a physical detector arises naturally and work and its statistics can be investigated in the most general case. In particular, we show that the quantum coherence of the initial state can lead to measurable effects on the moments of the work done on the system. At the same time, we recover the known results if the initial state is a statistical mixture of energy eigenstates. Our method can also be applied to measure the dissipated heat in an open quantum system. By sequentially coupling the system to a detector, we can track the energy dissipated in the environment while accessing only the system degrees of freedom. PMID- 26565212 TI - Aging and coarsening in isolated quantum systems after a quench: Exact results for the quantum O(N) model with N -> infinity. AB - The nonequilibrium dynamics of an isolated quantum system after a sudden quench to a dynamical critical point is expected to be characterized by scaling and universal exponents due to the absence of time scales. We explore these features for a quench of the parameters of a Hamiltonian with O(N) symmetry, starting from a ground state in the disordered phase. In the limit of infinite N, the exponents and scaling forms of the relevant two-time correlation functions can be calculated exactly. Our analytical predictions are confirmed by the numerical solution of the corresponding equations. Moreover, we find that the same scaling functions, yet with different exponents, also describe the coarsening dynamics for quenches below the dynamical critical point. PMID- 26565213 TI - Hydration of ions in two-dimensional water. AB - We present a two-dimensional lattice model of water to study the effects of ion hydration on the properties of water. We map the water molecules as lattice particles consisting of a single oxygen atom at the center of a site and two hydrogen atoms on each side. The internal state of the system, such as the dipole moment at a site, is defined with respect to the location of the hydrogen atoms at the site depending on their role in hydrogen bonds (H bonds) being a donor or an acceptor. We study the influence of the charge and the radius of the ion on the insertion energy and on the H bonds in the first and second hydration layers around the ion and in the bulk. In particular we analyze how the competing interactions of the short-ranged H bonds and the long-ranged electrostatics influence the hydration properties. The role of the ion both as a source of the electrostatic interactions as well as a defect is also discussed. Our model also shows the well-known fact that the polarizability of the water molecules destroys the hydrogen bond network and increases the dipole moment of the molecules near the ion. PMID- 26565214 TI - Index statistical properties of sparse random graphs. AB - Using the replica method, we develop an analytical approach to compute the characteristic function for the probability P(N)(K,lambda) that a large N*N adjacency matrix of sparse random graphs has K eigenvalues below a threshold lambda. The method allows to determine, in principle, all moments of P(N)(K,lambda), from which the typical sample-to-sample fluctuations can be fully characterized. For random graph models with localized eigenvectors, we show that the index variance scales linearly with N?1 for |lambda|>0, with a model dependent prefactor that can be exactly calculated. Explicit results are discussed for Erdos-Renyi and regular random graphs, both exhibiting a prefactor with a nonmonotonic behavior as a function of lambda. These results contrast with rotationally invariant random matrices, where the index variance scales only as lnN, with an universal prefactor that is independent of lambda. Numerical diagonalization results confirm the exactness of our approach and, in addition, strongly support the Gaussian nature of the index fluctuations. PMID- 26565215 TI - When the mean is not enough: Calculating fixation time distributions in birth death processes. AB - Studies of fixation dynamics in Markov processes predominantly focus on the mean time to absorption. This may be inadequate if the distribution is broad and skewed. We compute the distribution of fixation times in one-step birth-death processes with two absorbing states. These are expressed in terms of the spectrum of the process, and we provide different representations as forward-only processes in eigenspace. These allow efficient sampling of fixation time distributions. As an application we study evolutionary game dynamics, where invading mutants can reach fixation or go extinct. We also highlight the median fixation time as a possible analog of mixing times in systems with small mutation rates and no absorbing states, whereas the mean fixation time has no such interpretation. PMID- 26565216 TI - Melting in three-dimensional and two-dimensional Yukawa systems. AB - Solid-liquid phase transitions in three-dimensional (3D) and two-dimensional (2D) Yukawa systems were studied numerically and analytically, including the melting of the fcc and bcc 3D lattices, and of a hexagonal primitive (hp) 2D lattice. An approach is proposed for the determination of the melting lines in these systems. The suggested approach takes into account the nonlinearity (anharmonicity) of pair interaction forces and allows one to correctly predict the conditions of melting for 3D and 2D crystal systems. The obtained results are compared with the existing theoretical and numerical data. PMID- 26565217 TI - Levy flights with power-law absorption. AB - We consider a particle performing a stochastic motion on a one-dimensional lattice with jump lengths distributed according to a power law with exponent MU+1. Assuming that the walker moves in the presence of a distribution a(x) of targets (traps) depending on the spatial coordinate x, we study the probability that the walker will eventually find any target (will eventually be trapped). We focus on the case of power-law distributions a(x)~x(-alpha) and we find that, as long as MU=2d is qualitatively different: At lambda?4 long chains collapse into dense quasispherical globules and at lambda?8 these globules take toroidal configuration with a spontaneous azimuthal ordering of magnetic dipoles. With the increase of r(max) to larger values (r(max)>10d) globules expand and break down to form separate rings. PMID- 26565237 TI - Universal buckling kinetics in drying nanoparticle-laden droplets on a hydrophobic substrate. AB - We provide a comprehensive physical description of the vaporization, self assembly, agglomeration, and buckling kinetics of sessile nanofluid droplets pinned on a hydrophobic substrate. We have deciphered five distinct regimes of the droplet life cycle. Regimes I-III consists of evaporation-induced preferential agglomeration that leads to the formation of a unique dome-shaped inhomogeneous shell with a stratified varying-density liquid core. Regime IV involves capillary-pressure-initiated shell buckling and stress-induced shell rupture. Regime V marks rupture-induced cavity inception and growth. We demonstrate through scaling arguments that the growth of the cavity (which controls the final morphology or structure) can be described by a universal function. PMID- 26565238 TI - Self-replication with magnetic dipolar colloids. AB - Colloidal self-replication represents an exciting research frontier in soft matter physics. Currently, all reported self-replication schemes involve coating colloidal particles with stimuli-responsive molecules to allow switchable interactions. In this paper, we introduce a scheme using ferromagnetic dipolar colloids and preprogrammed external magnetic fields to create an autonomous self replication system. Interparticle dipole-dipole forces and periodically varying weak-strong magnetic fields cooperate to drive colloid monomers from the solute onto templates, bind them into replicas, and dissolve template complexes. We present three general design principles for autonomous linear replicators, derived from a focused study of a minimalist sphere-dimer magnetic system in which single binding sites allow formation of dimeric templates. We show via statistical models and computer simulations that our system exhibits nonlinear growth of templates and produces nearly exponential growth (low error rate) upon adding an optimized competing electrostatic potential. We devise experimental strategies for constructing the required magnetic colloids based on documented laboratory techniques. We also present qualitative ideas about building more complex self-replicating structures utilizing magnetic colloids. PMID- 26565239 TI - Understanding the approximations of mode-coupling theory for sheared steady states of colloids. AB - The lack of clarity of various mode-coupling theory (MCT) approximations, even in equilibrium, makes it hard to understand the relation between various MCT approaches for sheared steady states as well as their regime of validity. Here we try to understand these approximations indirectly by deriving the MCT equations through two different approaches for a colloidal system under shear, first through a microscopic approach, as suggested by Zaccarelli et al., and second through fluctuating hydrodynamics, where the approximations used in the derivation are quite clear. The qualitative similarity of our theory with a number of existing theories show that linear response theory might play a role in various approximations employed in deriving those theories and one needs to be careful while applying them for systems arbitrarily far away from equilibrium, such as a granular system or when shear is very strong. As a by-product of our calculation, we obtain the extension of the Yvon-Born-Green (YBG) equation for a sheared system and under the assumption of random-phase approximation, the YBG equation yields the distorted structure factor that was earlier obtained through different approaches. PMID- 26565240 TI - Interconversion algorithm between mechanical and dielectric relaxation measurements for acetate of cis- and trans-2-phenyl-5-hydroxymethyl-1,3-dioxane. AB - The dielectric and mechanical spectroscopies of acetate of cis- and trans-2 phenyl-5-hydroxymethyl-1,3-dioxane are reported in the frequency domain from 10( 2) to 10(6)Hz. This ester has been selected in this study for its predominant alpha relaxation with regard to the beta relaxation, which can be neglected. This study consists of determining an interconversion algorithm between dielectric and mechanical measurements, given by using a relation between rotational and translational complex viscosities. These important viscosities were obtained from measures of the dielectric complex permittivity and by dynamic mechanical analysis, respectively. The definitions of rotational and translational viscosities were evaluated by means of fractional calculus, by using the fit parameters of the Havriliak-Negami empirical model obtained in the dielectric and mechanical characterization of the alpha relaxation. This interconversion algorithm is a generalization of the break of the Stokes-Einstein-Debye relationship. It uses a power law with an exponent defined as the shape factor, which modifies the translational viscosity. Two others factors are introduced for the interconversion, a shift factor, which displaces the translational viscosity in the frequency domain, and a scale factor, which makes equal values of the two viscosities. In this paper, the shape factor has been identified as the relation between the slopes of the moduli of the complex viscosities at higher frequency. This is interpreted as the degree of kinetic coupling between the molecular rotation and translational movements. Alternatively, another interconversion algorithm has been expressed by means of dielectric and mechanical moduli. PMID- 26565241 TI - Dynamic dielectric response of electrorheological fluids in drag flow. AB - We have determined the response time of dilute electrorheological fluids (ER) in drag flow from the dynamic dielectric response. On the basis of a kinetic rate equation a new formula was derived to approximate the experimental time-dependent dielectric permittivity during the temporal evolution of the microstructure. The dielectric response time was compared to the standard rheological response time extracted from the time-dependent shear stress, and a good agreement was obtained. We found that the dielectric method is more sensitive to detect any transient during the chain formation process. The experimental saturation value of the dielectric permittivity corresponding to the equilibrium microstructure was estimated on the basis of formulas derived from the Clausius-Mossotti equation. PMID- 26565242 TI - Self-assembly of Janus particles into helices with tunable pitch. AB - Janus particles present an important class of building blocks for directional assembly. These are compartmentalized colloids with two different hemispheres. In this work we consider a three-dimensional model of Janus spheres that contain one hydrophobic and one charged hemisphere. Using molecular dynamics simulations, we study the morphology of these particles when confined in a channel-like environment. The interplay between the attractive and repulsive forces on each particle gives rise to a rich phase space where the relative orientation of each particle plays a dominant role in the formation of large-scale clusters. The interest in this system is primarily due to the fact that it could give a better understanding of the mechanisms of the formation of polar membranes. A variety of ordered membranelike morphologies is found consisting of single and multiple connected chain configurations. The helicity of these chains can be chosen by simply changing the salt concentration of the solution. Special attention is given to the formation of Bernal spirals. These helices are composed of regular tetrahedra and are known to exhibit nontrivial translational and rotational symmetry. PMID- 26565243 TI - Anisotropic pair correlations in binary and multicomponent hard-sphere mixtures in the vicinity of a hard wall: A combined density functional theory and simulation study. AB - The fundamental measure approach to classical density functional theory has been shown to be a powerful tool to predict various thermodynamic properties of hard sphere systems. We employ this approach to determine not only one-particle densities but also two-particle correlations in binary and six-component mixtures of hard spheres in the vicinity of a hard wall. The broken isotropy enables us to carefully test a large variety of theoretically predicted two-particle features by quantitatively comparing them to the results of Brownian dynamics simulations. Specifically, we determine and compare the one-particle density, the total correlation functions, their contact values, and the force distributions acting on a particle. For this purpose, we follow the compressibility route and theoretically calculate the direct correlation functions by taking functional derivatives. We usually observe an excellent agreement between theory and simulations, except for small deviations in cases where local crystal-like order sets in. Our results set the course for further investigations on the consistency of functionals as well as for structural analysis on, e.g., the primitive model. In addition, we demonstrate that due to the suppression of local crystallization, the predictions of six-component mixtures are better than those in bidisperse or monodisperse systems. Finally, we are confident that our results of the structural modulations induced by the wall lead to a deeper understanding of ordering in anisotropic systems in general, the onset of heterogeneous crystallization, caging effects, and glassy dynamics close to a wall, as well as structural properties in systems with confinement. PMID- 26565244 TI - Temperature dependence of the Soret coefficient of ionic colloids. AB - The temperature dependence of the Soret coefficient S(T)(T) in electrostatically charged magnetic colloids is investigated. Two different ferrofluids, with different particles' mean dimensions, are studied. In both cases we obtain a thermophilic behavior of the Soret effect. The temperature dependence of the Soret coefficient is described assuming that the nanoparticles migrate along the ionic thermoelectric field created by the thermal gradient. A model based on the contributions from the thermoelectrophoresis and variation of the double-layer energy, without fitting parameters, is used to describe the experimental results of the colloid with the bigger particles. To do so, independent measurements of the zeta potential, mass diffusion coefficient, and Seebeck coefficient are performed. The agreement of the theory and the experimental results is rather good. In the case of the ferrofluid with smaller particles, it is not possible to get experimentally reliable values of the zeta potential and the model described is used to evaluate this parameter and its temperature dependence. PMID- 26565245 TI - Rotational properties of ferromagnetic nanoparticles driven by a precessing magnetic field in a viscous fluid. AB - We study the deterministic and stochastic rotational dynamics of ferromagnetic nanoparticles in a precessing magnetic field. Our approach is based on the system of effective Langevin equations and on the corresponding Fokker-Planck equation. Two key characteristics of the rotational dynamics, namely the average angular frequency of precession of nanoparticles and their average magnetization, are of interest. Using the Langevin and Fokker-Planck equations, we calculate both analytically and numerically these characteristics in the deterministic and stochastic cases, determine their dependence on the model parameters, and analyze in detail the role of thermal fluctuations. PMID- 26565246 TI - Wall slip and fluidity in emulsion flow. AB - The microscopic origin of apparent wall slip is studied systematically using a confocal laser scanning microscope coupled to a rheometer. We obtain flow curves on a model emulsion from classical macroscopic measurements that are compared with flow curves obtained from microscopic measurements. By controlling the wetting properties of the shearing walls, we show that the characteristic length used in the so-called fluidity model, proposed by Goyon et al. [Nature (London) 454, 84 (2008)], can be understood in terms of roughness induced by adsorbed droplets on the surface. Additionally, we disentangle two different effects that contribute to the difference between micro- and macrorheology. Both effects manifest themselves as gap-dependent viscosities due to either the formation of a lubricating layer close to the shearing walls or cooperative effects when the flow is strongly confined. Finally, we show that the cooperative effects can also be translated into an effective slip velocity. PMID- 26565247 TI - Linear and nonlinear magnetic properties of ferrofluids. AB - Within a high-magnetic-field approximation, employing Ruelle's algebraic perturbation theory, a field-dependent free-energy expression is proposed which allows one to determine the magnetic properties of ferrofluids modeled as dipolar hard-sphere systems. We compare the ensuing magnetization curves, following from this free energy, with those obtained by Ivanov and Kuznetsova [Phys. Rev. E 64, 041405 (2001)] as well as with new corresponding Monte Carlo simulation data. Based on the power-series expansion of the magnetization, a closed expression for the magnetization is also proposed, which is a high-density extension of the corresponding equation of Ivanov and Kuznetsova. From both magnetization equations the zero-field susceptibility expression due to Tani et al. [Mol. Phys. 48, 863 (1983)] can be obtained, which is in good agreement with our MC simulation results. From the closed expression for the magnetization the second order nonlinear magnetic susceptibility is also derived, which shows fair agreement with the corresponding MC simulation data. PMID- 26565248 TI - Many-body critical Casimir interactions in colloidal suspensions. AB - We study the fluctuation-induced Casimir interactions in colloidal suspensions, especially between colloids immersed in a binary liquid close to its critical demixing point. To simulate these systems, we present a highly efficient cluster Monte Carlo algorithm based on geometric symmetries of the Hamiltonian. Utilizing the principle of universality, the medium is represented by an Ising system while the colloids are areas of spins with fixed orientation. Our results for the Casimir interaction potential between two particles at the critical point in two dimensions perfectly agree with the exact predictions. However, we find that in finite systems the behavior strongly depends on whether the Z(2) symmetry of the system is broken by the particles. We present Monte Carlo results for the three body Casimir interaction potential and take a close look onto the case of one particle in the vicinity of two adjacent particles, which can be calculated from the two-particle interaction by a conformal mapping. These results emphasize the failure of the common decomposition approach for many-particle critical Casimir interactions. PMID- 26565249 TI - Hypernetted-chain investigation of the random first-order transition of a Lennard Jones liquid to an ideal glass. AB - The structural and thermodynamic behavior of a deeply supercooled Lennard-Jones liquid, and its random first-order transition (RFOT) to an ideal glass is investigated, using a system of two weakly coupled replicas and the hypernetted chain integral equation for the pair structure of this symmetric binary system. A systematic search in the density-temperature plane points to the existence of two glass branches below a density-dependent threshold temperature. The branch of lower free energy exhibits a rapid growth of the structural overlap order parameter upon cooling and may be identified with the ideal glass phase conjectured by several authors for both spin and structural glasses. The RFOT, signaled by a sharp discontinuity of the order parameter, is predicted to be weakly first order from a thermodynamic viewpoint. The transition temperature T(cr) increases rapidly with density and approximately obeys a scaling relation valid for a reference system of particles interacting via a purely repulsive 1/r(18) potential. PMID- 26565250 TI - Generalization of Clausius-Mossotti approximation in application to short-time transport properties of suspensions. AB - In 1983, Felderhof, Ford, and Cohen gave microscopic explanation of the famous Clausius-Mossotti formula for the dielectric constant of nonpolar dielectric. They based their considerations on the cluster expansion of the dielectric constant, which relates this macroscopic property with the microscopic characteristics of the system. In this article, we analyze the cluster expansion of Felderhof, Ford, and Cohen by performing its resummation (renormalization). Our analysis leads to the ring expansion for the macroscopic characteristic of the system, which is an expression alternative to the cluster expansion. Using similarity of structures of the cluster expansion and the ring expansion, we generalize (renormalize) the Clausius-Mossotti approximation. We apply our renormalized Clausius-Mossotti approximation to the case of the short-time transport properties of suspensions, calculating the effective viscosity and the hydrodynamic function with the translational self-diffusion and the collective diffusion coefficient. We perform calculations for monodisperse hard-sphere suspensions in equilibrium with volume fraction up to 45%. To assess the renormalized Clausius-Mossotti approximation, it is compared with numerical simulations and the Beenakker-Mazur method. The results of our renormalized Clausius-Mossotti approximation lead to comparable or much less error (with respect to the numerical simulations) than the Beenakker-Mazur method for the volume fractions below phi~30% (apart from a small range of wave vectors in hydrodynamic function). For volume fractions above phi~30%, the Beenakker-Mazur method gives in most cases lower error than the renormalized Clausius-Mossotti approximation. PMID- 26565251 TI - Oscillatory cellular patterns in three-dimensional directional solidification. AB - We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in microgravity. Directional solidification experiments conducted onboard the International Space Station have allowed us to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 min. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelated at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (i.e., low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exists, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global disorder is observed in both three-dimensional experiments and simulations from realistic noisy initial conditions. In the latter case, erratic tip splitting events promoted by large-amplitude oscillations contribute to maintaining the long-range array disorder, unlike in thin-sample experiments where long-range coherence of oscillations is experimentally observable. PMID- 26565252 TI - Doughnut-shaped soap bubbles. AB - Soap bubbles are thin liquid films enclosing a fixed volume of air. Since the surface tension is typically assumed to be the only factor responsible for conforming the soap bubble shape, the realized bubble surfaces are always minimal area ones. Here, we consider the problem of finding the axisymmetric minimal area surface enclosing a fixed volume V and with a fixed equatorial perimeter L. It is well known that the sphere is the solution for V=L(3)/6pi(2), and this is indeed the case of a free soap bubble, for instance. Surprisingly, we show that for V